A
Abdominal aorta ultrasound see Abdominal
ultrasound
Abdominal aortic aneurysm see Aortic
aneurysm
Abdominal hernia see Hernia
Abdominal thrust see Heimlich maneuver

I Abdominal ultrasound
Definition
Ultrasound technology allows doctors to ‘‘see’’
inside a patient without resorting to surgery. A transmitter sends high frequency sound waves into the body,
where they bounce off the different tissues and organs
to produce a distinctive pattern of echoes. A receiver
‘‘hears’’ the returning echo pattern and forwards it to a
computer, which translates the data into an image on a
television screen. Because ultrasound can distinguish
subtle variations between soft, fluid-filled tissues, it is
particularly useful in providing diagnostic images of the
abdomen. Ultrasound can also be used in treatment.

Purpose
The potential medical applications of ultrasound
were first recognized in the 1940s as an outgrowth of
the sonar technology developed to detect submarines
during World War II. The first useful medical images
were produced in the early 1950s, and, by 1965, ultrasound quality had improved to the point that it came
into general medical use. Improvements in the technology, application, and interpretation of ultrasound
continue. Its low cost, versatility, safety and speed
have brought it into the top drawer of medical imaging
techniques.
GALE ENCYCLOPEDIA OF MEDICINE

While pelvic ultrasound is widely known and commonly used for fetal monitoring during pregnancy,
ultrasound is also routinely used for general abdominal imaging. It has great advantage over x-ray imaging technologies in that it does not damage tissues
with ionizing radiation. Ultrasound is also generally
far better than plain x rays at distinguishing the subtle
variations of soft tissue structures, and can be used in
any of several modes, depending on the need at hand.
As an imaging tool, abdominal ultrasound generally is warranted for patients afflicted with: chronic or
acute abdominal pain; abdominal trauma; an obvious
or suspected abdominal mass; symptoms of liver disease, pancreatic disease, gallstones, spleen disease, kidney disease and urinary blockage; or symptoms of an
abdominal aortic aneurysm. Specifically:


Abdominal pain. Whether acute or chronic, pain can
signal a serious problem–from organ malfunction or
injury to the presence of malignant growths.
Ultrasound scanning can help doctors quickly sort
through potential causes when presented with general or ambiguous symptoms. All of the major
abdominal organs can be studied for signs of disease
that appear as changes in size, shape and internal
structure.



Abdominal trauma. After a serious accident, such as
a car crash or a fall, internal bleeding from injured
abdominal organs is often the most serious threat to
survival. Neither the injuries nor the bleeding are
immediately apparent. Ultrasound is very useful as
an initial scan when abdominal trauma is suspected,
and it can be used to pinpoint the location, cause,
and severity of hemorrhaging. In the case of puncture wounds, from a bullet for example, ultrasound
can locate the foreign object and provide a preliminary survey of the damage. The easy portability and
versatility of ultrasound technology has brought it
into common emergency room use, and even into
limited ambulance service.
1

Abdominal ultrasound



Abdominal mass. Abnormal growths–tumors, cysts,
abscesses, scar tissue and accessory organs–can be
located and tentatively identified with ultrasound. In
particular, potentially malignant solid tumors can be
distinguished from benign fluid-filled cysts and
abscesses. Masses and malformations in any organ
or part of the abdomen can be found.



Liver disease. The types and underlying causes of
liver disease are numerous, though jaundice tends
to be a general symptom. Ultrasound can differentiate between many of the types and causes of liver
malfunction, and is particularly good at identifying
obstruction of the bile ducts and cirrhosis, which is
characterized by abnormal fibrous growths and
reduced blood flow.



Pancreatic disease. Inflammation and malformation
of the pancreas are readily identified by ultrasound,
as are pancreatic stones (calculi), which can disrupt
proper functioning.



Gallstones. Gallstones cause more hospital admissions
than any other digestive malady. These calculi can
cause painful inflammation of the gallbladder and
also obstruct the bile ducts that carry digestive enzymes
from the gallbladder and liver to the intestines.
Gallstones are readily identifiable with ultrasound.



Spleen disease. The spleen is particularly prone to
injury during abdominal trauma. It may also become
painfully inflamed when beset with infection or
cancer. These conditions also lend themselves well
to ultrasonic inspection and diagnosis.



Kidney disease. The kidneys are also prone to traumatic injury and are the organs most likely to form
calculi, which can block the flow of urine and cause
blood poisoning (uremia). A variety of diseases causing
distinct changes in kidney morphology can also lead to
complete kidney failure. Ultrasound imaging has proven extremely useful in diagnosing kidney disorders.



Abdominal aortic aneurysm. This is a bulging weak
spot in the abdominal aorta, which supplies blood
directly from the heart to the entire lower body.
These aneurysms are relatively common and increase
in prevalence with age. A burst aortic aneurysm is
imminently life-threatening. However, they can be
readily identified and monitored with ultrasound
before acute complications result.

Ultrasound technology can also be used for treatment purposes, most frequently as a visual aid during
surgical procedures–such as guiding needle placement
to drain fluid from a cyst, or to extract tumor cells for
biopsy. Increasingly, direct therapeutic applications
for ultrasound are being developed.
2

The direct therapeutic value of ultrasonic waves
lies in their mechanical nature. They are shock waves,
just like audible sound, and vibrate the materials
through which they pass. These vibrations are mild,
virtually unnoticeable at the frequencies and intensities used for imaging. Properly focused however, highintensity ultrasound can be used to heat and physically
agitate targeted tissues.
High-intensity ultrasound is used routinely to treat
soft tissue injuries, such as strains, tears and associated
scarring. The heating and agitation are believed to
promote rapid healing through increased circulation.
Strongly focused, high-intensity, high-frequency ultrasound can also be used to physically destroy certain
types of tumors, as well as gallstones and other types
of calculi. Developing new treatment applications
for ultrasound is an active area of medical research.

Precautions
Properly performed, ultrasound imaging is virtually without risk or side effects. Some patients report
feeling a slight tingling and/or warmth while being
scanned, but most feel nothing at all. Ultrasound
waves of appropriate frequency and intensity are not
known to cause or aggravate any medical condition,
though any woman who thinks she might be pregnant
should raise the issue with her doctor before undergoing an abdominal ultrasound.
The value of ultrasound imaging as a medical tool,
however, depends greatly on the quality of the equipment used and the skill of the medical personnel operating it. Improperly performed and/or interpreted,
ultrasound can be worse than useless if it indicates
that a problem exists where there is none, or fails to
detect a significant condition. Basic ultrasound equipment is relatively inexpensive to obtain, and any doctor with the equipment can perform the procedure
whether qualified or not. Patients should not hesitate
to verify the credentials of technicians and doctors
performing ultrasounds, as well as the quality of the
equipment used and the benefits of the proposed
procedure.
In cases where ultrasound is used as a treatment
tool, patients should educate themselves about the
proposed procedure with the help of their doctors–as
is appropriate before any surgical procedure. Also,
any abdominal ultrasound procedure, diagnostic or
therapeutic, may be hampered by a patient’s body
type or other factors, such as the presence of excessive
bowel gas (which is opaque to ultrasound). In particular, very obese people are often not good candidates
for abdominal ultrasound.
GALE ENCYCLOPEDIA OF MEDICINE

Abdominal ultrasound

KEY TERMS
Accessory organ—A lump of tissue adjacent to an
organ that is similar to it, but which serves no important purpose, if functional at all. While not necessarily harmful, such organs can cause problems if they
grow too large or become cancerous. In any case,
their presence points to an underlying abnormality in
the parent organ.
Benign—In medical usage, benign is the opposite of
malignant. It describes an abnormal growth that is
stable, treatable and generally not life-threatening.
Biopsy— The surgical removal and analysis of a
tissue sample for diagnostic purposes. Usually, the
term refers to the collection and analysis of tissue
from a suspected tumor to establish malignancy.
Calculus—Any type of hard concretion (stone) in the
body, but usually found in the gallbladder, pancreas
and kidneys. They are formed by the accumulation of
excess mineral salts and other organic material such
as blood or mucous. Calculi (pl.) can cause problems
by lodging in and obstructing the proper flow of fluids,
such as bile to the intestines or urine to the bladder.
Cirrhosis—A chronic liver disease characterized by
the invasion of connective tissue and the degeneration of proper functioning–jaundice is often an
accompanying symptom. Causes of cirrhosis include
alcoholism, metabolic diseases, syphilis and congestive heart disease.
Common bile duct—The branching passage through
which bile–a necessary digestive enzyme–travels
from the liver and gallbladder into the small intestine. Digestive enzymes from the pancreas also enter
the intestines through the common bile duct.
Computed tomography scan (CT scan)—A specialized type of x-ray imaging that uses highly focused
and relatively low energy radiation to produce detailed
two-dimensional images of soft tissue structures, particularly the brain. CT scans are the chief competitor to
ultrasound and can yield higher quality images not
disrupted by bone or gas. They are, however, more
cumbersome, time consuming and expensive to perform, and they use ionizing electromagnetic radiation.

Description
Ultrasound includes all sound waves above the
frequency of human hearing–about 20 thousand
hertz, or cycles per second. Medical ultrasound generally uses frequencies between one and 10 million hertz
GALE ENCYCLOPEDIA OF MEDICINE

Doppler—The Doppler effect refers to the apparent
change in frequency of sound wave echoes returning
to a stationary source from a moving target. If the
object is moving toward the source, the frequency
increases; if the object is moving away, the frequency decreases. The size of this frequency shift
can be used to compute the object’s speed–be it a
car on the road or blood in an artery. The Doppler
effect holds true for all types of radiation, not just
sound.
Frequency—Sound, whether traveling through air or
the human body, produces vibrations–molecules
bouncing into each other–as the shock wave travels
along. The frequency of a sound is the number of
vibrations per second. Within the audible range,
frequency means pitch–the higher the frequency,
the higher a sound’s pitch.
Ionizing radiation—Radiation that can damage living tissue by disrupting and destroying individual
cells at the molecular level. All types of nuclear
radiation–x rays, gamma rays and beta rays–are
potentially ionizing. Sound waves physically vibrate
the material through which they pass, but do not
ionize it.
Jaundice—A condition that results in a yellow tint to
the skin, eyes and body fluids. Bile retention in the
liver, gallbladder and pancreas is the immediate
cause, but the underlying cause could be as simple
as obstruction of the common bile duct by a gallstone or as serious as pancreatic cancer. Ultrasound
can distinguish between these conditions.
Malignant—The term literally means growing worse
and resisting treatment. It is used as a synonym for
cancerous and connotes a harmful condition that
generally is life-threatening.
Morphology—Literally, the study of form. In medicine, morphology refers to the size, shape and structure rather than the function of a given organ. As a
diagnostic imaging technique, ultrasound facilitates
the recognition of abnormal morphologies as symptoms of underlying conditions.

(1-10 MHz). Higher frequency ultrasound waves produce more detailed images, but are also more readily
absorbed and so cannot penetrate as deeply into the
body. Abdominal ultrasound imaging is generally performed at frequencies between 2-5 MHz.
3

Abdominal ultrasound

An ultrasound machine consists of two parts: the
transducer and the analyzer. The transducer both produces the sound waves that penetrate the body and
receives the reflected echoes. Transducers are built
around piezoelectric ceramic chips. (Piezoelectric
refers to electricity that is produced when you put
pressure on certain crystals such as quartz). These
ceramic chips react to electric pulses by producing
sound waves ( they are transmitting waves) and react
to sound waves by producing electric pulses (receiving). Bursts of high frequency electric pulses supplied
to the transducer causes it to produce the scanning
sound waves. The transducer then receives the returning echoes, translates them back into electric pulses
and sends them to the analyzer–a computer that organizes the data into an image on a television screen.
Because sound waves travel through all the body’s
tissues at nearly the same speed–about 3,400 miles per
hour–the microseconds it takes for each echo to be
received can be plotted on the screen as a distance into
the body. The relative strength of each echo, a function of the specific tissue or organ boundary that
produced it, can be plotted as a point of varying
brightness. In this way, the echoes are translated into
a picture. Tissues surrounded by bone or filled with
gas (the stomach, intestines and bowel) cannot be
imaged using ultrasound, because the waves are
blocked or become randomly scattered.
Four different modes of ultrasound are used in
medical imaging:


A-mode. This is the simplest type of ultrasound in
which a single transducer scans a line through the
body with the echoes plotted on screen as a function
of depth. This method is used to measure distances
within the body and the size of internal organs.
Therapeutic ultrasound aimed at a specific tumor
or calculus is also A-mode, to allow for pinpoint
accurate focus of the destructive wave energy.



B-mode. In B-mode ultrasound, a linear array of
transducers simultaneously scans a plane through
the body that can be viewed as a two-dimensional
image on screen. Ultrasound probes containing more
than 100 transducers in sequence form the basis for
these most commonly used scanners, which cost
about $50,000.



M-Mode. The M stands for motion. A rapid
sequence of B-mode scans whose images follow
each other in sequence on screen enables doctors to
see and measure range of motion, as the organ
boundaries that produce reflections move relative
to the probe. M-mode ultrasound has been put to
particular use in studying heart motion.

4



Doppler mode. Doppler ultrasonography includes the
capability of accurately measuring velocities of moving material, such as blood in arteries and veins. The
principle is the same as that used in radar guns that
measure the speed of a car on the highway. Doppler
capability is most often combined with B-mode scanning to produce images of blood vessels from which
blood flow can be directly measured. This technique
is used extensively to investigate valve defects, arteriosclerosis and hypertension, particularly in the
heart, but also in the abdominal aorta and the portal
vein of the liver. These machines cost about
$250,000.

The actual procedure for a patient undergoing an
abdominal ultrasound is relatively simple, regardless
of the type of scan or its purpose. Fasting for at least
eight hours prior to the procedure ensures that the
stomach is empty and as small as possible, and that
the intestines and bowels are relatively inactive.
Fasting also allows the gall bladder to be seen, as it
contracts after eating and may not be seen if the stomach is full. In some cases, a full bladder helps to push
intestinal folds out of the way so that the gas they
contain does not disrupt the image. The patient’s
abdomen is then greased with a special gel that allows
the ultrasound probe to glide easily across the skin
while transmitting and receiving ultrasonic pulses.
This procedure is conducted by a doctor with the
assistance of a technologist skilled in operating the
equipment. The probe is moved around the abdomen
to obtain different views of the target areas. The
patient will likely be asked to change positions from
side to side and to hold their breath as necessary to
obtain the desired views. Discomfort during the procedure is minimal.
The many types and uses of ultrasound technology makes it difficult to generalize about the time and
costs involved. Relatively simple imaging–scanning a
suspicious abdominal mass or a suspected abdominal
aortic aneurysm–will take about half an hour to perform and will cost a few hundred dollars or more,
depending on the quality of the equipment, the
operator and other factors. More involved techniques
such as multiple M-mode and Doppler-enhanced
scans, or cases where the targets not well defined in
advance, generally take more time and are more
expensive.
Regardless of the type of scan used and the potential
difficulties encountered, ultrasound remains faster and
less expensive than computed tomography scans (CT),
its primary rival in abdominal imaging. Furthermore, as
abdominal ultrasounds are generally undertaken as
GALE ENCYCLOPEDIA OF MEDICINE

Specific conditions for which ultrasound may be
selected as a treatment option–certain types of tumors,
lesions, kidney stones and other calculi, muscle and
ligament injuries, etc.–are described in detail under
the appropriate entries in this encyclopedia.

Preparation
A patient undergoing abdominal ultrasound will
be advised by their physician about what to expect and
how to prepare. As mentioned above, preparations
generally include fasting and arriving for the procedure with a full bladder, if necessary. This preparation
is particularly useful if the gallbladder, ovaries or veins
are to be examined.

Aftercare
In general, no aftercare related to the abdominal
ultrasound procedure itself is required.

Risks
Abdominal ultrasound carries with it no recognized risks or side effects, if properly performed using
appropriate frequency and intensity ranges. Sensitive
tissues, particularly those of the reproductive organs,
could possibly sustain damage if violently vibrated by
overly intense ultrasound waves. In general though,
such damage would only result from improper use of
the equipment.
Any woman who thinks she might be pregnant
should raise this issue with her doctor before undergoing an abdominal ultrasound, as a fetus in the early
stages of development could be injured by ultrasound
meant to probe deeply recessed abdominal organs.

Normal results
As a diagnostic imaging technique, a normal
abdominal ultrasound is one that indicates the absence
of the suspected condition that prompted the scan.
For example, symptoms such as a persistent cough,
labored breathing, and upper abdominal pain suggest
the possibility of, among other things, an abdominal
aortic aneurysm. An ultrasound scan that indicates
the absence of an aneurysm would rule out this lifeGALE ENCYCLOPEDIA OF MEDICINE

threatening condition and point to other, less serious
causes.

Abnormal results
Because abdominal ultrasound imaging is generally undertaken to confirm a suspected condition, the
results of a scan often will prove abnormal–that is they
will confirm the diagnosis, be it kidney stones, cirrhosis of the liver or an aortic aneurysm. At that point,
appropriate medical treatment as prescribed by a
patient’s doctor is in order. See the relevant disease
and disorder entries in this encyclopedia for more
information.
Resources
PERIODICALS

Freundlich, Naomi. ‘‘Ultrasound: What’s Wrong with this
Picture?’’ Business Week September 15, 1997:84-5.
ORGANIZATIONS

American College of Gastroenterology. 4900 B South 31st
St., Arlington, VA 22206-1656. (703) 820-7400.
<http://www.acg.gi.org>.
American Institute of Ultrasound in Medicine. 14750
Sweitzer Lane, Suite 100, Laurel, MD 20707-5906.
(800) 638-5352. <http://www.aium.org>.
American Society of Radiologic Technologists. 15000
Central Ave., SE, Albuquerque, NM 87123-3917. (505)
298-4500. <http://www.asrt.org>.

Kurt Richard Sternlof

I Abdominal wall defects
Definition
Abdominal wall defects are birth (congenital)
defects that allow the stomach or intestines to
protrude.

Description
Many unexpected and fascinating events occur
during the development of a fetus inside the womb.
The stomach and intestines begin development outside
the baby’s abdomen and only later does the abdominal
wall enclose them. Occasionally, either the umbilical
opening is too large, or it develops improperly, allowing the bowels or stomach to remain outside or
squeeze through the abdominal wall.
5

Abdominal wall defects

‘‘medically necessary’’ procedures designed to detect the
presence of suspected abnormalities, they are covered
under most types of major medical insurance. As always,
though, the patient would be wise to confirm that their
coverage extends to the specific procedure proposed.
For nonemergency situations, most underwriters stipulate prior approval as a condition of coverage.

Abortion, partial birth

Causes and symptoms
There are many causes for birth defects that still
remain unclear. Presently, the cause(s) of abdominal
wall defects is unknown, and any symptoms the
mother may have to indicate that the defects are present in the fetus are nondescript.

Diagnosis
At birth, the problem is obvious, because the base
of the umbilical cord at the navel will bulge or, in
worse cases, contain viscera (internal organs). Before
birth, an ultrasound examination may detect the problem. It is always necessary in children with one birth
defect to look for others, because birth defects are
usually multiple.

Treatment
Abdominal wall defects are effectively treated
with surgical repair. Unless there are accompanying
anomalies, the surgical procedure is not overly complicated. The organs are normal, just misplaced.
However, if the defect is large, it may be difficult to
fit all the viscera into the small abdominal cavity.

Prognosis
If there are no other defects, the prognosis after
surgical repair of this condition is relatively good.
However, 10% of those with more severe or additional
abnormalities die from it. The organs themselves
are fully functional; the difficulty lies in fitting them
inside the abdomen. The condition is, in fact, a hernia
requiring only replacement and strengthening of the
passageway through which it occurred. After surgery,
increased pressure in the stretched abdomen can compromise the function of the organs inside.

Prevention
Some, but by no means all, birth defects are preventable by early and attentive prenatal care, good
nutrition, supplemental vitamins, diligent avoidance
of all unnecessary drugs and chemicals–especially
tobacco–and other elements of a healthy lifestyle.
Resources
PERIODICALS

Dunn, J. C., and E. W. Fonkalsrud. ‘‘Improved Survival of
Infantswith Omphalocele.’’ American Journal of
Surgery 173 (April 1997): 284-7.

J. Ricker Polsdorfer, MD
6

KEY TERMS
Hernia—Movement of a structure into a place it
does not belong.
Umbilical—Referring to the opening in the abdominal wall where the blood vessels from the placenta
enter.
Viscera—Any of the body’s organs located in the
chest or abdomen.

Abnormal heart rhythms see Arrhythmias
ABO blood typing see Blood typing and
crossmatching
ABO incompatibility see Erythroblastosis
fetalis
Abortion, habitual see Recurrent
miscarriage

I Abortion, partial birth
Definition
Partial birth abortion is a method of late-term
(after 20 weeks) abortion that terminates a pregnancy
and results in the death and intact removal of a fetus.
This procedure is most commonly referred to as intact
dilatation and extraction (D & X). It occurs in a rare
percentage of pregnancies.

Purpose
Partial birth abortion, or D&X, is performed to
end a pregnancy and results in the death of a fetus,
typically in the late second or third trimester.
Although D&X is highly controversial, some physicians argue that it has advantages that make it a preferable procedure in some circumstances. One
perceived advantage is that the fetus is removed
largely intact, allowing for better evaluation and
autopsy of the fetus in cases of known fetal abnormalities. Intact removal of the fetus also may carry a lower
risk of puncturing the uterus or damaging the cervix.
Another perceived advantage is that D&X ends the
pregnancy without requiring the woman to go
through labor, which may be less emotionally traumatic than other methods of late-term abortion. In
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Women considering D&X should be aware of the
highly controversial nature of this procedure. A controversy common to all late-term abortions is whether
the fetus is viable, or able to survive outside of the
woman’s body. A specific area of controversy with
D&X is that fetal death does not occur until after
most of the fetal body has exited the uterus. Several
states have taken legal action to limit or ban D&X and
many physicians who perform abortions do not perform D&X. This may restrict the availability of this
procedure to women seeking late-term abortions.
In March 2003, the United States Senate passed a
bill banning partial birth abortions and implementing
fines or maximum two-year jail terms for physicians
who perform them. In June 2003, the House approved
a ban as well. President George W. Bush signed the
legislation into law, but a federal judge declared the
law unconstitutional, so that the government had not
been able to enforce it. One of the opponents’ claims
was the legislation did not provide for exceptions for
cases in which the procedure was needed to protect the
mother’s health.

Description
Intact D&X, or partial birth abortion first
involves administration of medications to cause the
cervix to dilate, usually over the course of several
days. Next, the physician rotates the fetus to a footling
breech position. The body of the fetus is then drawn
out of the uterus feet first, until only the head remains
inside the uterus. Then, the physician uses an instrument to puncture the base of the skull, which collapses
the fetal head. Typically, the contents of the fetal head
are then partially suctioned out, which results in the
death of the fetus and reduces the size of the fetal head
enough to allow it to pass through the cervix. The dead
and otherwise intact fetus is then removed from the
woman’s body.

Preparation
Medical preparation for D&X involves an outpatient visit to administer medications, such as laminaria, to cause the cervix to begin dilating.
In addition, preparation may involve fulfilling
local legal requirements, such as a mandatory waiting
period, counseling, or an informed consent procedure
GALE ENCYCLOPEDIA OF MEDICINE

Abortion, partial birth

addition, D&X may offer a lower cost and shorter
procedure time.

KEY TERMS
Cervix—The narrow outer end of the uterus that
separates the uterus from the vaginal canal.
Footling breech—A position of the fetus while in
the uterus where the feet of the fetus are nearest the
cervix and will be the first part of the fetus to exit the
uterus, with the head of the fetus being the last part
to exit the uterus.
Laminaria—A medical product made from a certain type of seaweed that is physically placed near
the cervix to cause it to dilate.

reviewing stages of fetal development, childbirth, alternative abortion methods, and adoption.

Aftercare
D&X typically does not require an overnight hospital stay, so a follow up appointment may be scheduled to monitor the woman for any complications.

Risks
With all abortion, the later in pregnancy an abortion is performed, the more complicated the procedure
and the greater the risk of injury to the woman. In
addition to associated emotional reactions, D&X carries the risk of injury to the woman, including heavy
bleeding, blood clots, damage to the cervix or uterus,
pelvic infection, and anesthesia-related complications.
There also is a risk of incomplete abortion, meaning
that the fetus is not dead when removed from the
woman’s body. Possible long-term risks include difficulty becoming pregnant or carrying a future pregnancy to term.

Normal results
The expected outcome of D&X is the termination
of a pregnancy with removal of a dead fetus from the
woman’s body.
Resources
PERIODICALS

‘‘Court Rules Abortion Ban Unconstitutional.’’ Medicine &
Health (June 7, 2004): 4–6.
‘‘House Approves Partial Birth Abortion Ban.’’ Medicine
and Health (June 16, 2003): 5.
‘‘Partial-birth Abortion Ban Approved by Senate.’’ Medical
Ethics Advisor (April 2003): 47.
7

Abortion, selective

ORGANIZATIONS

Planned Parenthood Federation of America, Inc.. 810
Seventh Ave., New York, NY 10019. (800) 669-0156.
<http://www.plannedparenthood.org>.
OTHER

Status of partial-birth abortion laws in the states. Othmer
Institute at Planned Parenthood of NYC. 2000.

Stefanie B. N. Dugan, M.S.
Teresa G. Odle

I Abortion, selective
Definition
Selective abortion, also known as selective reduction, refers to choosing to abort a fetus, typically in a
multi-fetal pregnancy, to decrease the health risks to
the mother in carrying and giving birth to more than
one or two babies, and also to decrease the risk of
complications to the remaining fetus(es). The term
selective abortion also refers to choosing to abort a
fetus for reasons such as the woman is carrying a fetus
which likely will be born with some birth defect or
impairment, or because the sex of the fetus is not
preferred by the individual.

Purpose
A woman may decide to abort for health reasons,
for example, she is at higher risk for complications
during pregnancy because of a disorder or disease
such as diabetes. A 2004 case reported on an embryo
embedded in a cesarean section scar. Although rare, it
can be life threatening to the mother. In this care,
selective abortion was successful at saving the mother
and the remaining embryos.
However, selective reduction is recommended
often in cases of multi-fetal pregnancy, or the presence
of more than one fetus, typically, at least three or more
fetuses. In the general population, multi-fetal pregnancy happens in only about 1-2% of pregnant
women. But multi-fetal pregnancies occur far more
often in women using fertility drugs.

KEY TERMS
Multi-fetal pregnancy—A pregnancy of two or
more fetuses.
Selective reduction—Typically referred to in cases
of multifetal pregnancy, when one or more fetuses
are aborted to preserve the viability of the remaining fetuses and decrease health risks to the mother.

cases of multi-fetal pregnancy. Individuals engaging in
fertility treatment should be made aware of the risk of
multi-fetal pregnancy and consider the prospect of
recommended reduction before undergoing fertility
treatment.

Description
Selective reduction is usually performed between
nine and 12 weeks of pregnancy and is most successful
when performed in early pregnancy. It is a simple
procedure and can be performed on an outpatient
basis. A needle is inserted into the woman’s stomach
or vagina and potassium chloride is injected into the
fetus.

Preparation
Individuals who have chosen selective reduction
to safeguard the remaining fetuses should be counseled prior to the procedure. Individuals should
receive information regarding the risks of a multifetal pregnancy to both the fetuses and the mother
compared with the risks after the reduction.
Individuals seeking an abortion for any reason
should consider the ethical implications whether it be
because the fetus is not the preferred sex or because the
fetus would be born with a severe birth defect.

Aftercare
Counseling should continue after the abortion
because it is a traumatic event. Individuals may feel
guilty about choosing one fetus over another. Mental
health professionals should be consulted throughout
the process.

Precautions
Because women or couples who use fertility drugs
have made an extra effort to become pregnant, it is
possible that the individuals may be unwilling or
uncomfortable with the decision to abort a fetus in
8

Risks
About 75% of women who undergo selective
reduction will go into premature labor. About 4-5%
of women undergoing selective reduction also
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
In cases where a multi-fetal pregnancy of three or
more fetuses is reduced to two fetuses, the remaining
twin fetuses typically develop as they would if they had
been conceived as twins.
Resources
PERIODICALS

‘‘Multiple Pregnancy Associated With Infertility Therapy.’’
American Society for Reproductive Medicine, A Practice
Committee Report (November 2000): 1-8.
‘‘Selective Reduction Eleiminates an Emryo Embedded
in a Cesarean Scar.’’ WomenÆs Health Weekly (April 8,
2004): 117.
ORGANIZATIONS

The Alan Guttmacher Institute. 120 Wall Street, New York,
NY 10005. (212) 248-1111. <http://www.agiusa.org>.
The American Society for Reproductive Medicine. 1209
Montgomery Highway, Birmingham, AL 35216-2809.
(205) 978-5000. <http://www.asrm.org>.

Meghan M. Gourley
Teresa G. Odle

gestational age and is used in determining the stage
of pregnancy. For example, a woman who is two
weeks late having her period is said to be six weeks
pregnant, because it is six weeks since she last
menstruated.
About 90% of women who have abortions do so
before 13 weeks and experience few complications.
Abortions performed between 13-24 weeks have a
higher rate of complications. Abortions after 24
weeks are extremely rare and are usually limited to
situations where the life of the mother is in danger.

Precautions
Most women are able to have abortions at clinics
or outpatient facilities if the procedure is performed
early in pregnancy. Women who have stable diabetes,
controlled epilepsy, mild to moderate high blood pressure, or who are HIV positive can often have abortions
as outpatients if precautions are taken. Women with
heart disease, previous endocarditis, asthma, lupus
erythematosus, uterine fibroid tumors, blood clotting
disorders, poorly controlled epilepsy, or some psychological disorders usually need to be hospitalized in
order to receive special monitoring and medications
during the procedure.

Description
Very early abortions

Abortion, spontaneous see Miscarriage

I Abortion, therapeutic
Definition
Therapeutic abortion is the intentional termination of a pregnancy before the fetus can live independently. Abortion has been a legal procedure in the
United States since 1973.

Purpose
An abortion may be performed whenever there is
some compelling reason to end a pregnancy. Women
have abortions because continuing the pregnancy
would cause them hardship, endanger their life or
health, or because prenatal testing has shown that
the fetus will be born with severe abnormalities.
Abortions are safest when performed within the
first six to 10 weeks after the last menstrual period.
The calculation of this date is referred to as the
GALE ENCYCLOPEDIA OF MEDICINE

Between five and seven weeks, a pregnancy can be
ended by a procedure called menstrual extraction.
This procedure is also sometimes called menstrual
regulation, mini-suction, or preemptive abortion.
The contents of the uterus are suctioned out through
a thin (3-4 mm) plastic tube that is inserted through the
undilated cervix. Suction is applied either by a bulb
syringe or a small pump.
Another method is called the ‘‘morning after’’ pill,
or emergency contraception. Basically, it involves taking high doses of birth control pills within 24 to 48
hours of having unprotected sex. The high doses of
hormones causes the uterine lining to change so that it
will not support a pregnancy. Thus, if the egg has been
fertilized, it is simply expelled from the body.
There are two types of emergency contraception.
One type is identical to ordinary birth control pills,
and uses the hormones estrogen and progestin). This
type is available with a prescription under the brand
name Preven. But women can even use their regular
birth control pills for emergency contraception, after
they check with their doctor about the proper dose.
About half of women who use birth control pills for
9

Abortion, therapeutic

miscarry one or more of the remaining fetuses. The
risks associated with multi-fetal pregnancy are considered higher.

Abortion, therapeutic

Vagina

Vulsellum

Uterus

Embryonic
tissue

Speculum
Extraction tube
Cervix
Between 5 and 7 weeks, a pregnancy can be ended by a procedure called menstrual extraction. The contents of the uterus are
suctioned out through a thin extraction tube that is inserted through the undilated cervix. (Illustration by Electronic Illustrators Group.)

KEY TERMS
Endocarditis—An infection of the inner membrane
lining of the heart.
Fibroid tumors—Fibroid tumors are non-cancerous
(benign) growths in the uterus. They occur in
30-40% of women over age 40, and do not need
to be removed unless they are causing symptoms
that interfere with a woman’s normal activities.
Lupus erythematosus—A chronic inflammatory
disease in which inappropriate immune system
reactions cause abnormalities in the blood vessels
and connective tissue.
Prostaglandin—Oxygenated unsaturated cyclic
fatty acids responsible for various hormonal reactions such as muscle contraction.
Rh negative—Lacking the Rh factor, genetically
determined antigens in red blood cells that produce
immune responses. If an Rh negative woman is
pregnant with an Rh positive fetus, her body will
produce antibodies against the fetus’s blood, causing a disease known as Rh disease. Sensitization to
the disease occurs when the women’s blood is
exposed to the fetus’s blood. Rh immune globulin
(RhoGAM) is a vaccine that must be given to a
woman after an abortion, miscarriage, or prenatal
tests in order to prevent sensitization to Rh disease.

10

emergency contraception get nauseated and 20 percent
vomit. This method cuts the risk of pregnancy 75percent.
The other type of morning-after pill contains only
one hormone: progestin, and is available under the
brand name Plan B. It is more effective than the first
type with a lower risk of nausea and vomiting. It
reduces the risk of pregnancy 89 percent.
Women should check with their physicians
regarding the proper dose of pills to take, as it depends
on the brand of birth control pill. Not all birth control
pills will work for emergency contraception.
Menstrual extractions are safe, but because the
amount of fetal material is so small at this stage of
development, it is easy to miss. This results in an incomplete abortion that means the pregnancy continues.
First trimester abortions
The first trimester of pregnancy includes the first
13 weeks after the last menstrual period. In the United
States, about 90% of abortions are performed during
this period. It is the safest time in which to have an
abortion, and the time in which women have the most
choice of how the procedure is performed.
MEDICAL ABORTIONS. Medical abortions are
brought about by taking medications that end the
pregnancy. The advantages of a first trimester medical
abortion are:

GALE ENCYCLOPEDIA OF MEDICINE

The procedure is non-invasive; no surgical instruments are used.



Anesthesia is not required.



Drugs are administered either orally or by injection.



The procedure resembles a natural miscarriage.
Disadvantages of a medical abortion are:



The effectiveness decreases after the seventh week.



The procedure may require multiple visits to the doctor.



Bleeding after the abortion lasts longer than after a
surgical abortion.



The woman may see the contents of her womb as it is
expelled.

Two different medications can be used to bring
about an abortion. Methotrexate (Rheumatrex) works
by stopping fetal cells from dividing which causes the
fetus to die.
On the first visit to the doctor, the woman receives
an injection of methotrexate. On the second visit,
about a week later, she is given misoprostol
(Cytotec), an oxygenated unsaturated cyclic fatty
acid responsible for various hormonal reactions such
as muscle contraction (prostaglandin), that stimulates
contractions of the uterus. Within two weeks, the
woman will expel the contents of her uterus, ending
the pregnancy. A follow-up visit to the doctor is necessary to assure that the abortion is complete.
With this procedure, a woman will feel cramping
and may feel nauseated from the misoprostol. This
combination of drugs is 90-96% effective in ending
pregnancy.
Mifepristone (RU-486), which goes by the brand
name Mifeprex, works by blocking the action of progesterone, a hormone needed for pregnancy to continue, then stimulates ulerine contractions thus ending
the pregnancy. It can be taken as much as 49 days after
the first day of a woman’s last period. On the first visit
to the doctor, a woman takes a mifepristone pill. Two
days later she returns and, if the miscarriage has not
occurred, takes two misoprostol pills, which causes the
uterus to contract. Five percent of women won’t need
to take misoprostol. After an observation period, she
returns home.
Within four days, 90% of women have expelled
the contents of their uterus and completed the abortion. Within 14 days, 95-97% of women have completed the abortion. A third follow-up visit to the
doctor is necessary to confirm through observation
or ultrasound that the procedure is complete. In the
event that it is not, a surgical abortion is performed.
GALE ENCYCLOPEDIA OF MEDICINE

Studies show that 4.5 to 8 percent of women need
surgery or a blood transfusion after taking mifepristone, and the pregnancy persists in about 1 percent of
women. In this case, surgical abortion is recommended because the fetus may be damanged. Side
effects include nausea, vaginal bleeding and heavy
cramping. The bleeding is typically heavier than a
normal period and may last up to 16 days.
Mifepristone is not recommended for women with
ectopic pregnancy, an IUD, who have been taking
long-term steroidal therapy, have bleeding abnormalities or on blood-thinners such as Coumadin.
Surgical abortions
First trimester surgical abortions are performed
using vacuum aspiration. The procedure is also called
dilation and evacuation (D & E), suction dilation,
vacuum curettage, or suction curettage.
Advantages of a vacuum aspiration abortion are:


It is usually done as a one-day outpatient procedure.



The procedure takes only 10-15 minutes.



Bleeding after the abortion lasts five days or less.



The woman does not see the products of her womb
being removed.
Disadvantages include:



The procedure is invasive; surgical instruments are
used.



Infection may occur.

During a vacuum aspiration, the woman’s cervix
is gradually dilated by expanding rods inserted into
the cervical opening. Once dilated, a tube attached to a
suction pump is inserted through the cervix and the
contents of the uterus are suctioned out. The procedure is 97-99% effective. The amount of discomfort a
woman feels varies considerably. Local anesthesia is
often given to numb the cervix, but it does not mask
uterine cramping. After a few hours of rest, the woman
may return home.
Second trimester abortions
Although it is better to have an abortion during
the first trimester, some second trimester abortions
may be inevitable. The results of genetic testing are
often not available until 16 weeks. In addition,
women, especially teens, may not have recognized
the pregnancy or come to terms with it emotionally
soon enough to have a first trimester abortion. Teens
make up the largest group having second trimester
abortions.
11

Abortion, therapeutic



Abortion, therapeutic

Some second trimester abortions are performed
as a D & E. The procedures are similar to those used
in the first trimester, but a larger suction tube must be
used because more material must be removed. This
increases the amount of cervical dilation necessary and
increases the risk of the procedure. Many physicians are
reluctant to perform a D & E this late in pregnancy, and
for some women is it not a medically safe option.
The alternative to a D & E in the second trimester
is an abortion by induced labor. Induced labor may
require an overnight stay in a hospital. The day before
the procedure, the woman visits the doctor for tests,
and to either have rods inserted in her cervix to help
dilate it or to receive medication that will soften the
cervix and speed up labor.
On the day of the abortion, drugs, usually prostaglandins to induce contractions, and a salt water
solution, are injected into the uterus. Contractions
begin, and within eight to 72 hours the woman delivers
the fetus.
Side effects of this procedure include nausea, vomiting, and diarrhea from the prostaglandins, and pain
from uterine cramps. Anesthesia of the sort used in
childbirth can be given to mask the pain. Many women
are able to go home a few hours after the procedure.
Very early abortions cost between $200-$400.
Later abortions cost more. The cost increases about
$100 per week between the thirteenth and sixteenth
week. Second trimester abortions are much more
costly because they often involve more risk, more
services, anesthesia, and sometimes a hospital stay.
Insurance carriers and HMOs may or may not cover
the procedure. Federal law prohibits federal funds
including Medicaid funds, from being used to pay for
an elective abortion.

Preparation
The doctor must know accurately the stage of a
woman’s pregnancy before an abortion is performed.
The doctor will ask the woman questions about her
menstrual cycle and also do a physical examination to
confirm the stage of pregnancy. This may be done at
an office visit before the abortion or on the day of the
abortion. Some states require a waiting period before
an abortion can be performed. Others require parental
or court consent for a child under age 18 to receive an
abortion.
Despite the fact that almost half of all women
in the United States have had at least one abortion
by the time they reach age 45, abortion is surrounded
by controversy. Women often find themselves in
12

emotional turmoil when deciding if an abortion is
a procedure they wish to undergo. Pre-abortion counseling is important in helping a woman resolve any
questions she may have about having the procedure.

Aftercare
Regardless of the method used to perform the
abortion, a woman will be observed for a period of
time to make sure her blood pressure is stable and
that bleeding is controlled. The doctor may prescribe
antibiotics to reduce the chance of infection. Women
who are Rh negative (lacking genetically determined
antigens in their red blood cells that produce immune
responses) should be given a human Rh immune
globulin (RhoGAM) after the procedure unless the
father of the fetus is also Rh negative. This prevents
blood incompatibility complications in future
pregnancies.
Bleeding will continue for about five days in a
surgical abortion and longer in a medical abortion.
To decrease the risk of infection, a woman should
avoid intercourse and not use tampons and douches
for two weeks after the abortion.
A follow-up visit is a necessary part of the
woman’s aftercare. Contraception will be offered to
women who wish to avoid future pregnancies, because
menstrual periods normally resume within a few
weeks.

Risks
Serious complications resulting from abortions
performed before 13 weeks are rare. Of the 90% of
women who have abortions in this time period, 2.5%
have minor complications that can be handled without
hospitalization. Less than 0.5% have complications
that require a hospital stay. The rate of complications
increases as the pregnancy progresses.
Complications from abortions can include:


uncontrolled bleeding



infection



blood clots accumulating in the uterus



a tear in the cervix or uterus



missed abortion where the pregnancy continues



incomplete abortion where some material from the
pregnancy remains in the uterus

Women who experience any of the following
symptoms of post-abortion complications should call
the clinic or doctor who performed the abortion
immediately.
GALE ENCYCLOPEDIA OF MEDICINE

severe pain



fever over 100.4 8F (38.2 8C)



heavy bleeding that soaks through more than one
sanitary pad per hour



foul-smelling discharge from the vagina



continuing symptoms of pregnancy

Abscess



Normal results
Usually the pregnancy is ended without complication and without altering future fertility.
Resources

An amoebic abscess caused by Entameoba histolytica.
(Phototake NYC. Reproduced by permission.)

BOOKS

Carlson, Karen J., Stephanie A. Eisenstat, and Terra
Ziporyn. ‘‘Abortion.’’ In The Harvard Guide to
Women’s Health. Cambridge, MA: Harvard University
Press, 1996.

Debra Gordon

Abrasions see Wounds

containing digested germs, digested tissue, white
blood cells, and enzymes.
An abscess is the last stage of a tissue infection
that begins with a process called inflammation.
Initially, as the invading germ activates the body’s
immune system, several events occur:


Blood flow to the area increases.



The temperature of the area increases due to the
increased blood supply.



I Abscess

The area swells due to the accumulation of water,
blood, and other liquids.



It turns red.

Definition



It hurts, because of the irritation from the swelling
and the chemical activity.

Abruptio placentae see Placental abruption

An abscess is an enclosed collection of liquefied
tissue, known as pus, somewhere in the body. It is the
result of the body’s defensive reaction to foreign
material.

Description
There are two types of abscesses, septic and sterile.
Most abscesses are septic, which means that they are
the result of an infection. Septic abscesses can occur
anywhere in the body. Only a germ and the body’s
immune response are required. In response to the
invading germ, white blood cells gather at the infected
site and begin producing chemicals called enzymes
that attack the germ by digesting it. These enzymes
act like acid, killing the germs and breaking them
down into small pieces that can be picked up by
the circulation and eliminated from the body.
Unfortunately, these chemicals also digest body tissues. In most cases, the germ produces similar chemicals. The result is a thick, yellow liquid–pus–
GALE ENCYCLOPEDIA OF MEDICINE

These four signs–heat, swelling, redness, and
pain–characterize inflammation.
As the process progresses, the tissue begins to turn
to liquid, and an abscess forms. It is the nature of an
abscess to spread as the chemical digestion liquefies
more and more tissue. Furthermore, the spreading
follows the path of least resistance–the tissues most
easily digested. A good example is an abscess just
beneath the skin. It most easily continues along
beneath the skin rather than working its way through
the skin where it could drain its toxic contents. The
contents of the abscess also leak into the general circulation and produce symptoms just like any other
infection. These include chills, fever, aching, and
general discomfort.
Sterile abscesses are sometimes a milder form
of the same process caused not by germs but by nonliving irritants such as drugs. If an injected drug
like penicillin is not absorbed, it stays where it was
13

Abscess

Specific types of abscesses

KEY TERMS
Cellulitis—Inflammation of tissue due to infection.
Enzyme—Any of a number of protein chemicals
that can change other chemicals.

Listed below are some of the more common and
important abscesses.


Carbuncles and other boils. Skin oil glands (sebaceous glands) on the back or the back of the neck
are the ones usually infected. The most common
germ involved is Staphylococcus aureus. Acne is a
similar condition of sebaceous glands on the face
and back.



Pilonidal abscess. Many people have as a birth defect
a tiny opening in the skin just above the anus. Fecal
bacteria can enter this opening, causing an infection
and subsequent abscess.



Retropharyngeal, parapharyngeal, peritonsillar
abscess. As a result of throat infections like strep
throat and tonsillitis, bacteria can invade the deeper
tissues of the throat and cause an abscess. These
abscesses can compromise swallowing and even
breathing.



Lung abscess. During or after pneumonia, whether
it’s due to bacteria [common pneumonia], tuberculosis, fungi, parasites, or other germs, abscesses can
develop as a complication.



Liver abscess. Bacteria or amoeba from the intestines
can spread through the blood to the liver and cause
abscesses.



Psoas abscess. Deep in the back of the abdomen on
either side of the lumbar spine lie the psoas muscles.
They flex the hips. An abscess can develop in one of
these muscles, usually when it spreads from the
appendix, the large bowel, or the fallopian tubes.

Fallopian tubes—Part of the internal female anatomy that carries eggs from the ovaries to the uterus.
Flora—Living inhabitants of a region or area.
Pyogenic—Capable of generating pus. Streptococcus,
Staphocococcus, and bowel bacteria are the primary
pyogenic organisms.
Sebaceous glands—Tiny structures in the skin that
produce oil (sebum). If they become plugged,
sebum collects inside and forms a nurturing place
for germs to grow.
Septicemia—The spread of an infectious agent
throughout the body by means of the blood stream.
Sinus—A tubular channel connecting one body
part with another or with the outside.

injected and may cause enough irritation to generate
a sterile abscess–sterile because there is no infection
involved. Sterile abscesses are quite likely to turn into
hard, solid lumps as they scar, rather than remaining
pockets of pus.

Causes and symptoms
Many different agents cause abscesses. The most
common are the pus-forming (pyogenic) bacteria like
Staphylococcus aureus, which is nearly always the
cause of abscesses under the skin. Abscesses near
the large bowel, particularly around the anus, may
be caused by any of the numerous bacteria found
within the large bowel. Brain abscesses and liver
abscesses can be caused by any organism that can
travel there through the circulation. Bacteria,
amoeba, and certain fungi can travel in this fashion.
Abscesses in other parts of the body are caused by
organisms that normally inhabit nearby structures or
that infect them. Some common causes of specific
abscesses are:


skin abscesses by normal skin flora



dental and throat abscesses by mouth flora



lung abscesses by normal airway flora, pneumonia
germs, or tuberculosis



abdominal and anal abscesses by normal bowel
flora

14

Diagnosis
The common findings of inflammation–heat, redness, swelling, and pain–easily identify superficial
abscesses. Abscesses in other places may produce
only generalized symptoms such as fever and discomfort. If the patient’s symptoms and physical examination do not help, a physician may have to resort to a
battery of tests to locate the site of an abscess, but
usually something in the initial evaluation directs the
search. Recent or chronic disease in an organ suggests
it may be the site of an abscess. Dysfunction of an
organ or system–for instance, seizures or altered bowel
function–may provide the clue. Pain and tenderness
on physical examination are common findings.
Sometimes a deep abscess will eat a small channel
(sinus) to the surface and begin leaking pus. A sterile
abscess may cause only a painful lump deep in the
buttock where a shot was given.
GALE ENCYCLOPEDIA OF MEDICINE

Since skin is very resistant to the spread of infection, it acts as a barrier, often keeping the toxic
chemicals of an abscess from escaping the body on
their own. Thus, the pus must be drained from the
abscess by a physician. The surgeon determines when
the abscess is ready for drainage and opens a path to
the outside, allowing the pus to escape. Ordinarily, the
body handles the remaining infection, sometimes with
the help of antibiotics or other drugs. The surgeon may
leave a drain (a piece of cloth or rubber) in the abscess
cavity to prevent it from closing before all the pus has
drained out.

Alternative treatment
If an abscess is directly beneath the skin, it will be
slowly working its way through the skin as it is more
rapidly working its way elsewhere. Since chemicals
work faster at higher temperatures, applications of
hot compresses to the skin over the abscess will hasten
the digestion of the skin and eventually result in its
breaking down, releasing the pus spontaneously. This
treatment is best reserved for smaller abscesses in relatively less dangerous areas of the body–limbs, trunk,
back of the neck. It is also useful for all superficial
abscesses in their very early stages. It will ‘‘ripen’’
them.
Contrast hydrotherapy, alternating hot and
cold compresses, can also help assist the body in
resorption of the abscess. There are two homeopathic remedies that work to rebalance the body in
relation to abscess formation, Silica and Hepar
sulphuris. In cases of septic abscesses, bentonite
clay packs (bentonite clay and a small amount of
Hydrastis powder) can be used to draw the infection
from the area.

case, the result is life threatening. Blood poisoning is a
term commonly used to describe an infection that has
spilled into the blood stream and spread throughout
the body from a localized origin. Blood poisoning,
known to physicians as septicemia, is also life
threatening.
Of special note, abscesses in the hand are more
serious than they might appear. Due to the intricate
structure and the overriding importance of the hand,
any hand infection must be treated promptly and
competently.

Prevention
Infections that are treated early with heat (if
superficial) or antibiotics will often resolve without
the formation of an abscess. It is even better to avoid
infections altogether by taking prompt care of open
injuries, particularly puncture wounds. Bites are the
most dangerous of all, even more so because they
often occur on the hand.
Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles
of Internal Medicine. New York: McGraw-Hill,
1997.

J. Ricker Polsdorfer, MD

Abscess drainage see Abscess incision and
drainage

I Abscess incision & drainage
Definition

Prognosis
Once the abscess is properly drained, the prognosis is excellent for the condition itself. The reason
for the abscess (other diseases the patient has) will
determine the overall outcome. If, on the other
hand, the abscess ruptures into neighboring areas or
permits the infectious agent to spill into the bloodstream, serious or fatal consequences are likely.
Abscesses in and around the nasal sinuses, face, ears,
and scalp may work their way into the brain.
Abscesses within an abdominal organ such as the
liver may rupture into the abdominal cavity. In either

GALE ENCYCLOPEDIA OF MEDICINE

An infected skin nodule that contains pus may
need to be drained via a cut if it does not respond to
antibiotics. This allows the pus to escape, and the
infection to heal.

Purpose
An abscess is a pus-filled sore, usually caused by a
bacterial infection. The pus is made up of both live and
dead organisms and destroyed tissue from the white
blood cells that were carried to the area to fight the
infection. Abscesses are often found in the soft tissue
under the skin, such as the armpit or the groin.

15

Abscess incision & drainage

Treatment

Abscess incision & drainage

Liver

Spleen

Stomach

Common sites of abscess
above and below the liver

Colon

Although abscesses are often found in the soft tissue under the skin, such as the armpit or the groin, they may develop in any
organ, such as the liver. (Illustration by Electronic Illustrators Group.)

However, they may develop in any organ, and are
commonly found in the breast and gums. Abscesses
are far more serious and call for more specific treatment if they are located in deep organs such as the
lung, liver or brain.
Because the lining of the abscess cavity tends
to interfere with the amount of the drug that can
penetrate the source of infection from the blood, the
cavity itself may require draining. Once an abscess has
fully formed, it often does not respond to antibiotics.
Even if the antibiotic does penetrate into the abscess, it
doesn’t function as well in that environment.

Precautions
An abscess can usually be diagnosed visually,
although an imaging technique such as a computed
tomography scan may be used to confirm the extent of
the abscess before drainage. Such procedures may also
be needed to localize internal abscesses, such as those
in the abdominal cavity or brain.
16

KEY TERMS
White blood cells—Cells that protect the body
against infection.

Description
A doctor will cut into the lining of the abscess,
allowing the pus to escape either through a drainage
tube or by leaving the cavity open to the skin. How big
the incision is depends on how quickly the pus is
encountered.
Once the abscess is opened, the doctor will clean
and irrigate the wound thoroughly with saline. If it is
not too large or deep, the doctor may simply pack the
abscess wound with gauze for 24–48 hours to absorb
the pus and discharge.
If it is a deeper abscess, the doctor may insert a
drainage tube after cleaning out the wound. Once the
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
The skin over the abscess will be cleansed by
swabbing gently with an antiseptic solution.

Aftercare
Much of the pain around the abscess will be gone
after the surgery. Healing is usually very fast. After the
tube is taken out, antibiotics may be continued for
several days. Applying heat and keeping the affected
area elevated may help relieve inflammation.

Risks
If there is any scarring, it is likely to become much
less noticeable as time goes on, and eventually almost
invisible. Occasionally, an abscess within a vital organ
(such as the brain) damages enough surrounding tissue
that there is some permanent loss of normal function.

Normal results
Most abscesses heal after drainage alone; others
require drainage and antibiotic drug treatment.
Resources
BOOKS

Turkington, Carol A., and Jeffrey S. Dover. Skin Deep. New
York: Facts on File, 1998.
ORGANIZATIONS

National Institute of Arthritis and Musculoskeletal and Skin
Diseases. 9000 Rockville Pike, Bldg. 31, Rm 9A04,
Bethesda, MD 20892.

Carol A. Turkington

I Abuse

Description
Physical abuse of a child is the infliction of injury
by another person. The injuries can include punching,
kicking, biting, burning, beating, or pulling the victim’s hair. The physical abuse inflicted on a child can
result in bruises, burns, poisoning, broken bones, and
internal hemorrhages. Physical assault against an
adult primarily occurs with women, usually in the
form of domestic violence. It is estimated that approximately three million children witness domestic violence every year.
Sexual abuse of a child refers to sexual behavior
between an adult and child or between two children,
one of whom is dominant or significantly older. The
sexual behaviors can include touching breasts, genitals, and buttocks; either dressed or undressed. The
behavior also can include exhibitionism, cunnilingus,
fellatio, or penetration of the vagina or anus with
sexual organs or objects.
Pornographic photography also is used in sexual
abuse with children. Reported sex offenders are 97%
male. Reports of child pornography have increased
since with the popularity of the Internet. Females
more often are perpetrators in child-care settings,
since children may confuse sexual abuse by a female
with normal hygiene care. The 1990s and early 2000s
were rocked by reports of sexual abuse of children
committed by Catholic priests. Most of the abuse
appeared to have occurred during the 1970s and a
prominent report released early in 2004 stated that as
many as 10.667 children were sexually abused by more
than 4,300 priests. Sexual abuse by stepfathers is five
times more common than with biological fathers.
Sexual abuse of daughters by stepfathers or fathers is
the most common form of incest.
Sexual abuse also can take the form of rape. The
legal definition of rape includes only slight penile
penetration in the victim’s outer vulva area.
Complete erection and ejaculation are not necessary.
Rape is the perpetration of an act of sexual intercourse
whether:


will is overcome by force or fear (from threats or by
use of drugs).



mental impairment renders the victim incapable of
rational judgment.



if the victim is below the legal age established for
consent.

Definition
Abuse is defined as anything that is harmful,
injurious, or offensive. Abuse also includes excessive
and wrongful misuse of a substance. There are several
major types of abuse: physical and sexual abuse of a
child or an adult, substance abuse, elderly abuse, and
emotional abuse.
GALE ENCYCLOPEDIA OF MEDICINE

Substance abuse is an abnormal pattern of substance usage leading to significant distress or impairment. The criteria include one or more of the following
occurring within a 12-month period:
17

Abuse

tube is in place, the surgeon closes the incision with
simple stitches, and applies a sterile dressing. Drainage
is maintained for several days to help prevent the
abscess from reforming.

Abuse

KEY TERMS
Encopresis—Abnormalities relating to bowel
movements that can occur as a result of stress or
fear.



recurrent substance use resulting in failure to fulfill
obligations at home, work, or school.



using substance in situations that are physically dangerous (i.e., while driving).



recurrent substance-related legal problems.



continued usage despite recurrent social and interpersonal problems (i.e., arguments and fights with
significant other).

Abuse of the elderly is common and occurs mostly
as a result of caretaker burnout, due to the high level
of dependency frail, elderly patients usually require.
Abuse can be manifested by physical signs, fear, and
delaying or not reporting the need for advanced medical care. Elderly patients also may exhibit financial
abuse (money or possessions taken away) and
abandonment.
Emotional abuse generally continues even after
physical assaults have stopped. In most cases it is a
personally tailored form of verbal or gesture abuse
expressed to illicit a provoked response.

Causes and symptoms
Children who have been abused usually have a
variety of symptoms that encompass behavioral, emotional, and psychosomatic problems (body problems
caused by emotional or mental disturbance). Children
who have been physically abused tend to be more
aggressive, angry, hostile, depressed, and have low
self-esteem. Additionally, they exhibit fear, anxiety,
and nightmares. Severe psychological problems may
result in suicidal behavior or posttraumatic stress disorder. Physically abused children may complain of
physical illness even in the absence of a cause. They
also may suffer from eating disorders and encopresis,
or involuntary defecation caused or psychic origin.
Children who are sexually abused may exhibit abnormal sexual behavior in the form of aggressiveness and
hyperarousal. Adolescents may display promiscuity,
sexual acting out, and—in some situations—homosexual contact.
Physical abuse directed towards adults can ultimately lead to death. Approximately 50% of women
18

murdered in the United States were killed by a former
or current male partner. Approximately one-third of
emergency room consultations by women were
prompted due to domestic violence. Female victims
who are married also have a higher rate of internal
injuries and unconsciousness than victims of stranger
assault (mugging, robbery). Physical abuse or rape
also can occur between married persons and persons
of the same gender. Perpetrators usually sexually
assault their victims to dominate, hurt, and debase
them. It is common for physical and sexual violence
to occur at the same time. A large percentage of sexually assaulted persons were also physically abused in
the form of punching, beating, or threatening the victim with a weapon such as a gun or knife. Usually
males who are hurt and humiliated tend to physically
assault people whom they are intimately involved
with, such as spouses and/or children. Males who
assault a female tend to have experienced or witnessed
violence during childhood. They also tend to abuse
alcohol, to be sexually assaultive, and are at increased
risk for assaultive behavior directed against children.
Jealous males tend to monitor a women’s movements
and whereabouts and to isolate other sources of protection and support. They interpret their behavior as
betrayal of trust and this causes resentment and explosive anger outbursts during periods of losing control.
Males also may use aggression against females in an
effort to control and intimidate partners.
Abuse in the elderly usually occurs in the frail,
elderly community. The caretaker is usually the perpetrator. Caretaker abuse can be suspected if there is
evidence suggesting behavioral changes in the elderly
person when the caretaker is present. Additionally,
elderly abuse can be possible if there are delays
between injuries and treatment, inconsistencies
between injury and explanations, lack of hygiene or
clothing, and prescriptions not being filled.

Diagnosis
Children who are victims of domestic violence
frequently are injured attempting to protect their
mother from an abusive partner. Injuries are visible
by inspection or self-report. Physical abuse of an adult
may also be evident by inspection with visible cuts
and/or bruises or self-report.
Sexual abuse of both a child and an adult can be
diagnosed with a history from the victim. Victims can
be assessed for signs of ejaculatory evidence from the
perpetrator. Ejaculatory specimens can be retrieved
from the mouth, rectum, and clothing. Tests for sexually transmitted diseases may be performed.
GALE ENCYCLOPEDIA OF MEDICINE

Substance abuse can be suspected in a person who
continues to indulge in their drug of choice despite
recurrent negative consequences. The diagnosis can
be made after administration of a comprehensive
exam and standardized chemical abuse assessments
by a therapist.

Treatment
Children who are victims of physical or sexual
abuse typically require psychological support and
medical attention. A complaint may be filed with the
local family social services agency that will initiate
investigations. The authorities usually will follow up
the allegation or offense. Children may also be
referred for psychological evaluation and/or treatment. The victim also may be placed in foster care
pending the investigation outcome. The police also
may investigate physical and sexual abuse of an
adult. The victim may require immediate medical
care and long-term psychological treatment. It is common for children to be adversely affected by domestic
violence situations and the local family services agency
may be involved.
Substance abusers should elect treatment, either
inpatient or outpatient, depending on severity of
addiction. Long term treatment and/or medications
may be utilized to assist in abstinence. The patient
should be encouraged to participate in community
centered support groups.

Prognosis
The prognosis depends on the diagnosis.
Usually victims of physical and sexual abuse require
therapy to deal with emotional distress associated
with the incident. Perpetrators require further psychological evaluation and treatment. Victims of
abuse may have a variety of emotional problems
including depression, acts of suicide, or anxiety.
Children of sexual abuse may enter abusive relationships or have problems with intimacy as adults.
The substance abuser may experience relapses, since
the cardinal feature of all addictive disorders is a
tendency to return to symptoms. Elderly patients
may suffer from further medical problems and/or
anxiety, and in some cases neglect may precipitate
death.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Prevention programs are geared to education and
awareness. Detection of initial symptoms or characteristic behaviors may assist in some situations. In
some cases treatment may be sought before incident.
The professional treating the abused persons must
develop a clear sense of the relationship dynamics
and the chances for continued harm.
Resources
BOOKS

Behrman, Richard E., et al, editors. Nelson Textbook of
Pediatrics. 16th ed. W. B. Saunders Company, 2000.
PERIODICALS

Plante, Thomas G. ‘‘Another Aftershock: What Have We
Learned from the John Jay Report?.’’ America (March
22, 2004): 10.
ORGANIZATIONS

National Clearinghouse on Child Abuse and Neglect
Information. 330 C Street SW, Washington, DC 20447.
(800) 392-3366.
OTHER

Elder Abuse Prevention. <http://www.oaktrees.org/
elder>.
National Institute on Drug Abuse. <http://
www.nida.nih.gov>.

Laith Farid Gulli, M.D.
Bilal Nasser, M.Sc.
Teresa G. Odle

Acceleration-deceleration cervical injury see
Whiplash
ACE inhibitors see Angiotensin-converting
enzyme inhibitors

I Acetaminophen
Definition
Acetaminophen is a medicine used to relieve pain
and reduce fever.

Purpose
Acetaminophen is used to relieve many kinds of
minor aches and pains—headaches, muscle aches,
backaches, toothaches, menstrual cramps, arthritis,
and the aches and pains that often accompany colds.
19

Acetaminophen

Elderly abuse can be suspected if the elderly patient
demonstrates a fear of the caretaker. Additionally,
elderly abuse can be suspected if there are signs indicating intentional delay of required medical care or a
change in medical status.

Acetaminophen

Description
This drug is available without a prescription.
Acetaminophen is sold under various brand names,
including Tylenol, Panadol, Aspirin Free Anacin, and
Bayer Select Maximum Strength Headache Pain Relief
Formula. Many multi-symptom cold, flu, and sinus
medicines also contain acetaminophen. The ingredients listing on the container should state if acetaminophen is included in the product.
Studies have shown that acetaminophen relieves
pain and reduces fever about as well as aspirin. But
differences between these two common drugs exist.
Acetaminophen is less likely than aspirin to irritate
the stomach. However, unlike aspirin, acetaminophen
does not reduce the redness, stiffness, or swelling that
accompany arthritis.

Recommended dosage
The usual dosage for adults and children age 12
and over is 325-650 mg every four to six hours as
needed. No more than 4 grams (4000 mg) should be
taken in 24 hours. Because the drug can potentially
harm the liver, people who drink alcohol in large
quantities should take considerably less acetaminophen and possibly should avoid the drug completely.
For children ages 6-11 years, the usual dose is 150300 mg, three to four times a day. A physician should
recommend doses for children under age 6 years.

Precautions
In 2004, the U.S. Food and Drug Administration
(FDA) launched an advertising campaign aimed at
educating consumers about proper use of acetaminophen and other over-the-counter pain killers. Often,
acetaminophen is hidden in many cold and flu products
and people unexpectedly overdose on the medicine.
Some cases have led to liver transplantation or death.
More than the recommended dosage of acetaminophen
should not be taken unless told to do so by a physician
or dentist.
Patients should not use acetaminophen for more
than 10 days to relieve pain (five days for children) or
for more than three days to reduce fever, unless directed to do so by a physician. If symptoms do not go
away—or if they get worse— a physician should be
contacted. Anyone who drinks three or more alcoholic
beverages a day should check with a physician before
using this drug and should never take more than the
recommended dosage. A risk of liver damage exists
from combining large amounts of alcohol and
20

KEY TERMS
Arthritis—Inflammation of the joints. The condition causes pain and swelling.
Fatigue—Physical or mental weariness.
Inflammation—A response to irritation, infection,
or injury, resulting in pain, redness, and swelling.

acetaminophen. People who already have kidney or
liver disease or liver infections should also consult with
a physician before using the drug. So should women
who are pregnant or breastfeeding.
Many drugs can interact with one another. A
physician or pharmacist should be consulted before
combining acetaminophen with any other medicine.
Two different acetaminophen-containing products
should not be used at the same time.
Acetaminophen interferes with the results of some
medical tests. Avoiding the drug for a few days before
the tests may be necessary.

Side effects
Acetaminophen causes few side effects. The most
common one is lightheadedness. Some people may
experience trembling and pain in the side or the
lower back. Allergic reactions occur in some people,
but are rare. Anyone who develops symptoms such as
a rash, swelling, or difficulty breathing after taking
acetaminophen should stop taking the drug and get
immediate medical attention. Other rare side effects
include yellow skin or eyes, unusual bleeding or bruising, weakness, fatigue, bloody or black stools, bloody
or cloudy urine, and a sudden decrease in the amount
of urine.
Overdoses of acetaminophen may cause nausea,
vomiting, sweating, and exhaustion. Very large overdoses can cause liver damage. In case of an overdose,
immediate medical attention should be sought. In
2004, researchers announced that an injection to counteract the liver injury caused by acetaminophen overdose has been approved by the FDA.

Interactions
Acetaminophen may interact with a variety of
other medicines. When this happens, the effects of one
or both of the drugs may change or the risk of side
effects may be greater. Among the drugs that may
interact with acetaminophen are alcohol, nonsteroidal
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Causes
Achalasia is caused by degeneration of the nerve
cells that normally signal the brain to relax the
esophageal sphincter. The ultimate cause of this
degeneration is unknown. Autoimmune disease or
hidden infection is suspected.
Symptoms

Resources
PERIODICALS

‘‘Antidote Cleared for Acetiminophen Overdose.’’ Drug
Topics February 23, 2004: 12.
Mechcatie, Elizabeth. ‘‘FDA Launches Campaign About
OTC Drug Risks: NSAIDs, Acetaminophen.’’ Family
Practice News March 15, 2004: 8l

Nancy Ross-Flanigan
Teresa G. Odle

Dysphagia, or difficulty swallowing, is the most
common symptom of achalasia. The person with
achalasia usually has trouble swallowing both liquid
and solid foods, often feeling that food ‘‘gets stuck’’
on the way down. The person has chest pain that
is often mistaken for angina pectoris (cardiac pain).
Heartburn and difficulty belching are common.
Symptoms usually get steadily worse. Other symptoms
may include nighttime cough or recurrent pneumonia
caused by food passing into the lower airways.

Acetylsalicylic acid see Aspirin

I Achalasia
Definition

Diagnosis
Diagnosis of achalasia begins with a careful medical history. The history should focus on the timing of
symptoms and on eliminating other medical conditions that may cause similar symptoms. Tests used to
diagnose achalasia include:


Esophageal manometry. In this test, a thin tube is
passed into the esophagus to measure the pressure
exerted by the esophageal sphincter.



X ray of the esophagus. Barium may be swallowed to
act as a contrast agent. Barium reveals the outlines of
the esophagus in greater detail and makes it easier to
see its constriction at the sphincter.



Endoscopy. In this test, a tube containing a lens and a
light source is passed into the esophagus. Endoscopy is
used to look directly at the surface of the esophagus.
This test can also detect tumors that cause symptoms
like those of achalasia. Cancer of the esophagus occurs
as a complication of achalasia in 2-7% of patients.

Achalasia is a disorder of the esophagus that
prevents normal swallowing.

Description
Achalasia affects the esophagus, the tube that
carries swallowed food from the back of the throat
down into the stomach. A ring of muscle called the
lower esophageal sphincter encircles the esophagus
just above the entrance to the stomach. This sphincter
muscle is normally contracted to close the esophagus.
When the sphincter is closed, the contents of the stomach cannot flow back into the esophagus. Backward
flow of stomach contents (reflux) can irritate and
inflame the esophagus, causing symptoms such as
heartburn. The act of swallowing causes a wave of
esophageal contraction called peristalsis. Peristalsis
pushes food along the esophagus. Normally, peristalsis causes the esophageal sphincter to relax and allow
food into the stomach. In achalasia, which means
‘‘failure to relax,’’ the esophageal sphincter remains
contracted. Normal peristalsis is interrupted and food
cannot enter the stomach.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
The first-line treatment for achalasia is balloon
dilation. In this procedure, an inflatable membrane
or balloon is passed down the esophagus to the sphincter and inflated to force the sphincter open. Dilation is
effective in about 70% of patients.
Three other treatments are used for achalasia when
balloon dilation is inappropriate or unacceptable.
21

Achalasia

anti-inflammatory drugs (NSAIDs) such as Motrin,
oral contraceptives, the antiseizure drug phenytoin
(Dilantin), the blood-thinning drug warfarin
(Coumadin), the cholesterol-lowering drug cholestyramine (Questran), the antibiotic Isoniazid, and zidovudine (Retrovir, AZT). A physician or pharmacist
should be consulted before combining acetaminophen
with any other prescription or nonprescription (overthe-counter) medicine.

Achondroplasia

Prevention

KEY TERMS
Botulinum toxin—Any of a group of potent bacterial toxins or poisons produced by different strains of
the bacterium Clostridium botulinum. The toxins
cause muscle paralysis.
Dysphagia—Difficulty in swallowing.

There is no known way to prevent achalasia.
Resources
BOOKS

Grendell, James H., Kenneth R. McQuaid, and Scott L.
Friedman, editors. Current Diagnosis and Treatment in
Gastroenterology. Stamford: Appleton& Lange, 1996.

Endoscopy—A test in which a viewing device
and a light source are introduced into the esophagus by means of a flexible tube. Endoscopy permits visual inspection of the esophagus for
abnormalities.
Esophageal manometry—A test in which a thin
tube is passed into the esophagus to measure the
degree of pressure exerted by the muscles of the
esophageal wall.
Esophageal sphincter—A circular band of muscle
that closes the last few centimeters of the esophagus and prevents the backward flow of stomach
contents.
Esophagomyotomy—A surgical incision through
the muscular tissue of the esophagus.
Esophagus—The muscular tube that leads from the
back of the throat to the entrance of the stomach.
Peristalsis—The coordinated, rhythmic wave of
smooth muscle contraction that forces food
through the digestive tract.
Reflux—An abnormal backward or return flow of a
fluid.



Botulinum toxin injection. Injected into the sphincter, botulinum toxin paralyzes the muscle and allows
it to relax. Symptoms usually return within one to
two years.



Esophagomyotomy. This surgical procedure cuts the
sphincter muscle to allow the esophagus to open.
Esophagomyotomy is becoming more popular with
the development of techniques allowing very small
abdominal incisions.



Drug therapy. Nifedipine, a calcium-channel blocker,
reduces muscle contraction. Taken daily, this drug
provides relief for about two-thirds of patients for as
long as two years.

Richard Robinson

I Achondroplasia
Definition
Achondroplasia is the most common cause of
dwarfism, or significantly abnormal short stature.

Description
Achondroplasia is one of a number of chondodystrophies, in which the development of cartilage,
and therefore, bone is disturbed. The disorder
appears in approximately one in every 10,000
births. Achondroplasia is usually diagnosed at birth,
owing to the characteristic appearance of the
newborn.
Normal bone growth depends on the production of cartilage (a fibrous connective tissue). Over
time, calcium is deposited within the cartilage,
causing it to harden and become bone. In achondroplasia, abnormalities of this process prevent the
bones (especially those in the limbs) from growing
as long as they normally should, at the same time
allowing the bones to become abnormally thickened. The bones in the trunk of the body and the
skull are mostly not affected, although the opening
from the skull through which the spinal cord
passes (foramen magnum) is often narrower than
normal, and the opening (spinal canal) through
which the spinal cord runs in the back bones (vertebrae) becomes increasingly and abnormally small
down the length of the spine.

Causes and symptoms
Prognosis
Most patients with achalasia can be treated effectively. Achalasia does not reduce life expectancy
unless esophageal carcinoma develops.
22

Achondroplasia is caused by a genetic defect. It is
a dominant trait, meaning that anybody with
the genetic defect will display all the symptoms of
the disorder. A parent with the disorder has a 50%
GALE ENCYCLOPEDIA OF MEDICINE

Cartilage—A flexible, fibrous type of connective
tissue which serves as a base on which bone is
built.
Foramen magnum—The opening at the base of the
skull, through which the spinal cord and the brainstem pass.
Hydrocephalus—An abnormal accumulation of
fluid within the brain. This accumulation can be
destructive by pressing on brain structures, and
damaging them.
Mutation—A new, permanent change in the structure of a gene, which can result in abnormal structure or function somewhere in the body.
Spinal canal—The opening that runs through the
center of the column of spinal bones (vertebrae),
and through which the spinal cord passes.
An x-ray image of an achondroplastic person’s head
and chest. (Custom Medical Stock Photo. Reproduced by
permission.)

chance of passing it on to the offspring. Although
achondroplasia can be passed on to subsequent
offspring, the majority of cases occur due to a new
mutation (change) in a gene. Interestingly enough,
the defect seen in achondroplasia is one of only a
few defects known to increase in frequency with
increasing age of the father (many genetic defects are
linked to increased age of the mother).
People with achondroplasia have abnormally
short arms and legs. Their trunk is usually of normal
size, as is their head. The appearance of short limbs
and normal head size actually makes the head
appear to be oversized. The bridge of the nose
often has a scooped out appearance termed ‘‘saddle
nose.’’ The lower back has an abnormal curvature,
or sway back. The face often displays an overly
prominent forehead, and a relative lack of development of the face in the area of the upper jaw. Because
the foramen magnum and spinal canal are abnormally narrowed, nerve damage may occur if the
spinal cord or nerves become compressed. The narrowed foramen magnum may disrupt the normal
flow of fluid between the brain and the spinal cord,
resulting in the accumulation of too much fluid in
the brain (hydrocephalus). Children with achondroplasia have a very high risk of serious and repeated
middle ear infections, which can result in hearing
loss. The disease does not affect either mental capacity, or reproductive ability.
GALE ENCYCLOPEDIA OF MEDICINE

Vertebrae—The individual bones of the spinal column which are stacked on top of each other. There
is a hole in the center of each bone, through which
the spinal cord passes.

Diagnosis
Diagnosis is often made at birth due to the characteristically short limbs, and the appearance of a
large head. X-ray examination will reveal a characteristic appearance to the bones, with the bones of the
limbs appearing short in length, yet broad in width. A
number of measurements of the bones in x-ray images
will reveal abnormal proportions.

Treatment
No treatment will reverse the defect present in
achondroplasia. All patients with the disease will be
short, with abnormally proportioned limbs, trunk,
and head. Treatment of achondroplasia primarily
addresses some of the complications of the disorder,
including problems due to nerve compression, hydrocephalus, bowed legs, and abnormal curves in the
spine. Children with achondroplasia who develop
middle ear infections (acute otitis media) will require
quick treatment with antibiotics and careful monitoring in order to avoid hearing loss.

Prognosis
Achondroplasia is a disease which causes considerable deformity. However, with careful attention
23

Achondroplasia

KEY TERMS

Acid phosphatase test

paid to the development of dangerous complications
(nerve compression, hydrocephalus), most people are
in good health, and can live a normal lifespan.

Prevention
The only form of prevention is through genetic
counseling, which could help parents assess their risk
of having a child with achondroplasia.

KEY TERMS
Enzyme—A substance needed to trigger specific
chemical reactions.
Metastasize—Spread to other parts of the body;
usually refers to cancer.
Prostate gland—A gland of the male reproductive
system.

Resources
BOOKS

Krane, Stephen M., and Alan L. Schiller.
‘‘Achondroplasia.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.
ORGANIZATIONS

Little People of America, c/o Mary Carten. 7238 Piedmont
Drive, Dallas, TX 75227-9324. (800) 243-9273.

Rosalyn Carson-DeWitt, MD

Achromatopsia see Color blindness
Acid indigestion see Heartburn

Tissues other than prostate have small amounts
of acid phosphatase, including bone, liver, spleen,
kidney, and red blood cells and platelets. Damage to
these tissues causes a moderate increase in acid phosphatase levels.
Acid phosphatase is very concentrated in semen.
Rape investigations will often include testing for the
presence of acid phosphatase in vaginal fluid.

Precautions
This is not a screening test for prostate cancer.
Acid phosphatase levels rise only after prostate cancer
has metastasized.

Description

I Acid phosphatase test
Definition
Acid phosphatase is an enzyme found throughout
the body, but primarily in the prostate gland. Like all
enzymes, it is needed to trigger specific chemical reactions. Acid phosphatase testing is done to diagnose
whether prostate cancer has spread to other parts of
the body (metastasized), and to check the effectiveness
of treatment. The test has been largely supplanted by
the prostate specific antigen test (PSA).

Purpose
The male prostate gland has 100 times more
acid phosphatase than any other body tissue.
When prostate cancer spreads to other parts of the
body, acid phosphatase levels rise, particularly if
the cancer spreads to the bone. One-half to threefourths of persons who have metastasized prostate
cancer have high acid phosphatase levels. Levels fall
after the tumor is removed or reduced through
treatment.
24

Laboratory testing measures the amount of acid
phosphatase in a person’s blood, and can determine
from what tissue the enzyme is coming. For example, it
is important to know if the increased acid phosphatase
is from the prostate or red blood cells. Acid phosphatase from the prostate, called prostatic acid phosphatase (PAP), is the most medically significant type of
acid phosphatase.
Subtle differences between prostatic acid phosphatase and acid phosphatases from other tissues
cause them to react differently in the laboratory
when mixed with certain chemicals. For example,
adding the chemical tartrate to the test mixture inhibits the activity of prostatic acid phosphatase but not
red blood cell acid phosphatase. Laboratory test
methods based on these differences reveal how
much of a person’s total acid phosphatase is derived
from the prostate. Results are usually available the
next day.

Preparation
This test requires drawing about 5-10 mL of blood.
The patient should not have a rectal exam or prostate
massage for two to three days prior to the test.
GALE ENCYCLOPEDIA OF MEDICINE

Description

Discomfort or bruising may occur at the puncture
site, and the person may feel dizzy or faint. Applying
pressure to the puncture site until the bleeding stops
will reduce bruising. Warm packs to the puncture site
will relieve discomfort.

Normal results
Normal results vary based on the laboratory and
the method used.

Abnormal results
The highest levels of acid phosphatase are found
in metastasized prostate cancer. Diseases of the
bone, such as Paget’s disease or hyperparathyroidism;
diseases of blood cells, such as sickle cell disease or
multiple myeloma; or lysosomal disorders, such as
Gaucher’s disease, will show moderately increased
levels.
Certain medications can cause temporary increases
or decreases in acid phosphatase levels. Manipulation
of the prostate gland through massage, biopsy, or rectal
exam before a test can increase the level.
Resources
PERIODICALS

Moul, Judd W., et al. ‘‘The Contemporary Value of
Pretreatment Prostatic Acid Phosphatase to Predict
Pathological Stage and Recurrence in Radical
Prostatectomy Cases.’’ Journal of Urology (March
1998): 935-940.

Nancy J. Nordenson

Acne vulgaris, the medical term for common acne,
is the most common skin disease. It affects nearly 17
million people in the United States. While acne can
arise at any age, it usually begins at puberty and worsens during adolescence. Nearly 85% of people
develop acne at some time between the ages of 12-25
years. Up to 20% of women develop mild acne. It is
also found in some newborns.
The sebaceous glands lie just beneath the skin’s
surface. They produce an oil called sebum, the skin’s
natural moisturizer. These glands and the hair follicles
within which they are found are called sebaceous
follicles. These follicles open onto the skin through
pores. At puberty, increased levels of androgens
(male hormones) cause the glands to produce too
much sebum. When excess sebum combines with
dead, sticky skin cells, a hard plug, or comedo, forms
that blocks the pore. Mild noninflammatory acne consists of the two types of comedones, whiteheads and
blackheads.
Moderate and severe inflammatory types of acne
result after the plugged follicle is invaded by
Propionibacterium acnes, a bacteria that normally
lives on the skin. A pimple forms when the damaged
follicle weakens and bursts open, releasing sebum,
bacteria, and skin and white blood cells into the surrounding tissues. Inflamed pimples near the skin’s surface are called papules; when deeper, they are called
pustules. The most severe type of acne consists of cysts
(closed sacs) and nodules (hard swellings). Scarring
occurs when new skin cells are laid down to replace
damaged cells.
The most common sites of acne are the face, chest,
shoulders, and back since these are the parts of the
body where the most sebaceous follicles are found.

Acid reflux see Heartburn
Acidosis see Respiratory acidosis; Renal
tubular acidosis; Metabolic acidosis

I Acne

Causes and symptoms
The exact cause of acne is unknown. Several risk
factors have been identified:


Age. Due to the hormonal changes they experience,
teenagers are more likely to develop acne.



Gender. Boys have more severe acne and develop it
more often than girls.



Disease. Hormonal disorders can complicate acne in
girls.



Heredity. Individuals with a family history of acne
have greater susceptibility to the disease.



Hormonal changes. Acne can flare up before menstruation, during pregnancy, and menopause.

Definition
Acne is a common skin disease characterized by
pimples on the face, chest, and back. It occurs when
the pores of the skin become clogged with oil, dead
skin cells, and bacteria.
GALE ENCYCLOPEDIA OF MEDICINE

25

Acne

Aftercare

Acne

KEY TERMS
Androgens—Male sex hormones that are linked
with the development of acne.
Antiandrogens—Drugs that inhibit the production
of androgens.
Antibiotics—Medicines that kill bacteria.
Comedo—A hard plug composed of sebum and
dead skin cells. The mildest type of acne.
Comedolytic—Drugs that break up comedones
and open clogged pores.
Corticosteroids—A group of hormones produced
by the adrenal glands with different functions,
including regulation of fluid balance, androgen
activity, and reaction to inflammation.
Estrogens—Hormones produced by the ovaries,
the female sex glands.
Isotretinoin—A drug that decreases sebum production and dries up acne pimples.
Sebaceous follicles—A structure found within the
skin that houses the oil-producing glands and hair
follicles, where pimples form.
Sebum—An oily skin moisturizer produced by
sebaceous glands.
Tretinoin—A drug that works by increasing the
turnover (death and replacement) of skin cells.
Acne vulgaris affecting a woman’s face. Acne is the general
name given to a skin disorder in which the sebaceous glands
become inflamed. (Photograph by Biophoto Associates, Photo
Researchers, Inc. Reproduced by permission.)



Diet. No foods cause acne, but certain foods may
cause flare-ups.



Drugs. Acne can be a side effect of drugs including
tranquilizers, antidepressants, antibiotics, oral contraceptives, and anabolic steroids.



Personal hygiene. Abrasive soaps, hard scrubbing, or
picking at pimples will make them worse.



Cosmetics. Oil-based makeup and hair sprays worsen acne.



Environment. Exposure to oils and greases, polluted
air, and sweating in hot weather aggravate acne.



Stress. Emotional stress may contribute to acne.

Acne is usually not conspicuous, although inflamed lesions may cause pain, tenderness, itching, or
swelling. The most troubling aspects of these lesions
are the negative cosmetic effects and potential for
26

scarring. Some people, especially teenagers, become
emotionally upset about their condition, and have
problems forming relationships or keeping jobs.

Diagnosis
Acne patients are often treated by family doctors.
Complicated cases are referred to a dermatologist, a
skin disease specialist, or an endocrinologist, a specialist who treats diseases of the body’s endocrine (hormones and glands) system.
Acne has a characteristic appearance and is not
difficult to diagnose. The doctor takes a complete
medical history, including questions about skin care,
diet, factors causing flare-ups, medication use, and
prior treatment. Physical examination includes the
face, upper neck, chest, shoulders, back, and other
affected areas. Under good lighting, the doctor determines what types and how many blemishes are present, whether they are inflamed, whether they are deep
or superficial, and whether there is scarring or skin
discoloration.
GALE ENCYCLOPEDIA OF MEDICINE

Laboratory tests are not done unless the patient
appears to have a hormonal disorder or other medical
problem. In this case, blood analyses or other tests
may be ordered. Most insurance plans cover the
costs of diagnosing and treating acne.

Treatment
Acne treatment consists of reducing sebum production, removing dead skin cells, and killing bacteria
with topical drugs and oral medications. Treatment
choice depends upon whether the acne is mild, moderate, or severe.
Drugs
TOPICAL DRUGS. Treatment for mild noninflammatory acne consists of reducing the formation of new
comedones with topical tretinoin, benzoyl peroxide,
adapalene, or salicylic acid. Tretinoin is especially
effective because it increases turnover (death and
replacement) of skin cells. When complicated by
inflammation, topical antibiotics may be added to the
treatment regimen. Improvement is usually seen in
two to four weeks.

Topical medications are available as cream, gel,
lotion, or pad preparations of varying strengths.
They include antibiotics (agents that kill bacteria),
such as erythromycin, clindamycin (Cleocin-T), and
meclocycline (Meclan); comedolytics (agents that
loosen hard plugs and open pores) such as the vitamin
A acid tretinoin (Retin-A), salicylic acid, adapalene
(Differin), resorcinol, and sulfur. Drugs that act as
both comedolytics and antibiotics, such as benzoyl
peroxide, azelaic acid (Azelex), or benzoyl peroxide
plus erythromycin (Benzamycin), are also used.
These drugs may be used for months to years to
achieve disease control.
After washing with mild soap, the drugs are
applied alone or in combination, once or twice a day
over the entire affected area of skin. Possible side
effects include mild redness, peeling, irritation, dryness, and an increased sensitivity to sunlight that
requires use of a sunscreen.
ORAL DRUGS. Oral antibiotics are taken daily for
two to four months. The drugs used include tetracycline,

GALE ENCYCLOPEDIA OF MEDICINE

erythromycin, minocycline (Minocin), doxycycline,
clindamycin (Cleocin), and trimethoprim- sulfamethoxazole (Bactrim, Septra). Possible side effects include
allergic reactions, stomach upset, vaginal yeast infections, dizziness, and tooth discoloration.
The goal of treating moderate acne is to decrease
inflammation and prevent new comedone formation.
One effective treatment is topical tretinoin along with
a topical or oral antibiotic. A combination of topical
benzoyl peroxide and erythromycin is also very effective. Improvement is normally seen within four to six
weeks, but treatment is maintained for at least two to
four months.
A drug reserved for the treatment of severe
acne, oral isotretinoin (Accutane), reduces sebum
production and cell stickiness. It is the treatment
of choice for severe acne with cysts and nodules,
and is used with or without topical or oral antibiotics. Taken for four to five months, it provides longterm disease control in up to 60% of patients. If the
acne reappears, another course of isotretinoin may
be needed by about 20% of patients, while another
20% may do well with topical drugs or oral antibiotics. Side effects include temporary worsening of
the acne, dry skin, nosebleeds, vision disorders, and
elevated liver enzymes, blood fats and cholesterol.
This drug must not be taken during pregnancy since
it causes birth defects.
Anti-androgens, drugs that inhibit androgen production, are used to treat women who are unresponsive to other therapies. Certain types of oral
contraceptives (for example, Ortho-Tri-Cyclen) and
female sex hormones (estrogens) reduce hormone
activity in the ovaries. Other drugs, for example, spironolactone and corticosteroids, reduce hormone
activity in the adrenal glands. Improvement may
take up to four months.
Oral corticosteroids, or anti-inflammatory drugs,
are the treatment of choice for an extremely severe,
but rare type of destructive inflammatory acne called
acne fulminans, found mostly in adolescent males.
Acne conglobata, a more common form of severe
inflammation, is characterized by numerous, deep,
inflammatory nodules that heal with scarring. It is
treated with oral isotretinoin and corticosteroids.
Other treatments
Several surgical or medical treatments are available to alleviate acne or the resulting scars:


Comedone extraction. The comedo is removed from
the pore with a special tool.
27

Acne

In teenagers, acne is often found on the forehead,
nose, and chin. As people get older, acne tends to
appear towards the outer part of the face. Adult
women may have acne on their chins and around
their mouths. The elderly may develop whiteheads
and blackheads on the upper cheeks and skin around
the eyes.

Acoustic neuroma



Chemical peels. Glycolic acid is applied to peel off
the top layer of skin to reduce scarring.



unless told otherwise, give dry pimples a limited
amount of sun exposure



Dermabrasion. The affected skin is frozen with a
chemical spray, and removed by brushing or planing.



do not pick or squeeze blemishes



reduce stress



Punch grafting. Deep scars are excised and the area
repaired with small skin grafts.



Intralesional injection. Corticosteroids are injected
directly into inflamed pimples.



Collagen injection. Shallow scars are elevated by
collagen (protein) injections.

Alternative treatment
Alternative treatments for acne focus on proper
cleansing to keep the skin oil-free; eating a wellbalanced diet high in fiber, zinc, and raw foods; and
avoiding alcohol, dairy products, smoking, caffeine,
sugar, processed foods, and foods high in iodine,
such as salt. Supplementation with herbs such as
burdock root (Arctium lappa), red clover (Trifolium
pratense), and milk thistle (Silybum marianum), and
with nutrients such as essential fatty acids, vitamin B
complex, zinc, vitamin A, and chromium is also
recommended. Chinese herbal remedies used for
acne include cnidium seed (Cnidium monnieri) and
honeysuckle flower (Lonicera japonica). Wholistic
physicians or nutritionists can recommend the proper
amounts of these herbs.

Prognosis
Acne is not curable, although long-term control is
achieved in up to 60% of patients treated with isotretinoin. It can be controlled by proper treatment, with
improvement taking two or more months. Acne tends
to reappear when treatment stops, but spontaneously
improves over time. Inflammatory acne may leave
scars that require further treatment.

Prevention
There are no sure ways to prevent acne, but the
following steps may be taken to minimize flare-ups:


gentle washing of affected areas once or twice every
day



avoid abrasive cleansers



use noncomedogenic makeup and moisturizers



shampoo often and wear hair off face



eat a well-balanced diet, avoiding foods that trigger
flare-ups

28

Resources
PERIODICALS

Billings, Laura. ‘‘Getting Clear.’’ Health Magazine (April
1997): 48-52.
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.

Mercedes McLaughlin

Acne rosacea see Rosacea
Acoustic neurinoma see Acoustic neuroma

I Acoustic neuroma
Definition
An acoustic neuroma is a benign tumor involving
cells of the myelin sheath that surrounds the vestibulocochlear nerve (eighth cranial nerve).

Description
The vestibulocochlear nerve extends from the
inner ear to the brain and is made up of a vestibular
branch, often called the vestibular nerve, and a
cochlear branch, called the cochlear nerve. The vestibular and cochlear nerves lie next to one another. They
also run along side other cranial nerves. People possess
two of each type of vestibulocochlear nerve, one that
extends from the left ear and one that extends from the
right ear.
The vestibular nerve transmits information concerning balance from the inner ear to the brain and the
cochlear nerve transmits information about hearing.
The vestibular nerve, like many nerves, is surrounded
by a cover called a myelin sheath. A tumor, called
a schwannoma, can sometimes develop from the cells
of the myelin sheath. A tumor is an abnormal growth
of tissue that results from the uncontrolled growth of
cells. Acoustic neuromas are often called vestibular
schwannomas because they are tumors that arise
GALE ENCYCLOPEDIA OF MEDICINE

An acoustic neuroma can arise from the left
vestibular nerve or the right vestibular nerve. A unilateral tumor is a tumor arising from one nerve and
a bilateral tumor arises from both vestibular nerves.
Unilateral acoustic neuromas usually occur spontaneously (by chance). Bilateral acoustic neuromas
occur as part of a hereditary condition called
Neurofibromatosis Type 2 (NF2). A person with
NF2 has inherited a predisposition for developing acoustic neuromas and other tumors of the
nerve cells.
Acoustic neuromas usually grow slowly and
can take years to develop. Some acoustic neuromas
remain so small that they do not cause any symptoms. As the acoustic neuroma grows it can interfere with the functioning of the vestibular nerve
and can cause vertigo and balance difficulties. If
the acoustic nerve grows large enough to press
against the cochlear nerve, then hearing loss and
a ringing (tinnitus) in the affected ear will usually
occur. If untreated and the acoustic neuroma continues to grow it can press against other nerves in
the region and cause other symptoms. This tumor
can be life threatening if it becomes large enough
to press against and interfere with the functioning
of the brain.

Causes and symptoms
Causes

KEY TERMS
Benign tumor—A localized overgrowth of cells
that does not spread to other parts of the body.
Chromosome—A microscopic structure, made of a
complex of proteins and DNA, that is found within
each cell of the body.
Computed tomography (CT)—An examination
that uses a computer to compile and analyze the
images produced by x rays projected at a particular
part of the body.
Cranial nerves—The set of twelve nerves found on
each side of the head and neck that control the
sensory and muscle functions of a number of organs
such as the eyes, nose, tongue face and throat.
DNA testing—Testing for a change or changes in a
gene or genes.
Gene— A building block of inheritance, made up
of a compound called DNA (deoxyribonucleic
acid) and containing the instructions for the production of a particular protein. Each gene is found
on a specific location on a chromosome.
Magnetic resonance imaging (MRI)—A test which
uses an external magnetic field instead of x rays to
visualize different tissues of the body.
Myelin sheath—The cover that surrounds many
nerve cells and helps to increase the speed by
which information travels along the nerve.
Neurofibromatosis type 2 (NF2)—A hereditary
condition associated with an increased risk of bilateral acoustic neuromas, other nerve cell tumors
and cataracts.
Protein— A substance produced by a gene that is
involved in creating the traits of the human body
such as hair and eye color or is involved in controlling the basic functions of the human body.

An acoustic neuroma is caused by a change or
absence of both of the NF2 tumor suppressor genes
in a nerve cell. Every person possesses a pair of NF2
genes in every cell of their body including their nerve
cells. One NF2 gene is inherited from the egg cell of the
mother and one NF2 gene is inherited from the sperm
cell of the father. The NF2 gene is responsible for
helping to prevent the formation of tumors in the
nerve cells. In particular the NF2 gene helps to prevent
acoustic neuromas.

Schwannoma—A tumor derived from the cells of
the myelin sheath that surrounds many nerve cells.
Tinnitus—A ringing sound or other noise in the ear.

Only one unchanged and functioning NF2 gene
is necessary to prevent the formation of an acoustic
neuroma. If both NF2 genes become changed or
missing in one of the myelin sheath cells of the

vestibular nerve then an acoustic neuroma will usually
develop. Most unilateral acoustic neuromas result
when the NF2 genes become spontaneously changed
or missing. Someone with a unilateral acoustic

GALE ENCYCLOPEDIA OF MEDICINE

Vertigo—A feeling of spinning or whirling.
Vestibulocochlear nerve (Eighth cranial nerve)—
Nerve that transmits information, about hearing
and balance from the ear to the brain.

29

Acoustic neuroma

from the myelin sheath that surrounds the vestibular
nerve. Acoustic neuromas are considered benign
(non-cancerous) tumors since they do not spread
to other parts of the body. They can occur anywhere along the vestibular nerve but are most likely
to occur where the vestibulocochlear nerve passes
through the tiny bony canal that connects the brain
and the inner ear.

Acoustic neuroma

neuroma that has developed spontaneously is not at
increased risk for having children with an acoustic
neuroma. Some unilateral acoustic neuromas result
from the hereditary condition NF2. It is also possible
that some unilateral acoustic neuromas may be caused
by changes in other genes responsible for preventing
the formation of tumors.
Bilateral acoustic neuromas result when someone is affected with the hereditary condition NF2.
A person with NF2 is typically born with one
unchanged and one changed or missing NF2 gene
in every cell of their body. Sometimes they inherit
this change from their mother or father. Sometimes
the change occurs spontaneously when the egg and
sperm come together to form the first cell of the
baby. The children of a person with NF2 have a
50% chance of inheriting the changed or missing
NF2 gene.
A person with NF2 will develop an acoustic neuroma if the remaining unchanged NF2 gene becomes
spontaneously changed or missing in one of the myelin
sheath cells of their vestibular nerve. People with NF2
often develop acoustic neuromas at a younger age.
The mean age of onset of acoustic neuroma in NF2
is 31 years of age versus 50 years of age for sporadic
acoustic neuromas. Not all people with NF2, however,
develop acoustic neuromas. People with NF2 are at
increased risk for developing cataracts and tumors in
other nerve cells.
Most people with a unilateral acoustic neuroma
are not affected with NF2. Some people with NF2,
however, only develop a tumor in one of the vestibulocochlear nerves. Others may initially be diagnosed
with a unilateral tumor but may develop a tumor in the
other nerve a number of years later. NF2 should be
considered in someone under the age of 40 who has a
unilateral acoustic neuroma. Someone with a unilateral acoustic neuroma and other family members
diagnosed with NF2 probably is affected with NF2.
Someone with a unilateral acoustic neuroma and
other symptoms of NF2 such as cataracts and other
tumors may also be affected with NF2. On the other
hand, someone over the age of 50 with a unilateral
acoustic neuroma, no other tumors and no family
history of NF2 is very unlikely to be affected
with NF2.
Recent studies in Europe have suggested a possible connection between the widespread use of mobile
phones and an increased risk of developing acoustic
neuromas. Some observers, however, question
whether mobile phones have been in use long enough
to be an identifiable risk factor.
30

Symptoms
Small acoustic neuromas usually only interfere
with the functioning of the vestibulocochlear nerve.
The most common first symptom of an acoustic neuroma is hearing loss, which is often accompanied by a
ringing sound (tinnitis). People with acoustic neuromas sometimes report difficulties in using the phone
and difficulties in perceiving the tone of a musical
instrument or sound even when their hearing appears
to be otherwise normal. In most cases the hearing loss
is initially subtle and worsens gradually over time
until deafness occurs in the affected ear. In approximately 10% of cases the hearing loss is sudden and
severe.
Acoustic neuromas can also affect the functioning of the vestibular branch of the vestibulocochlear
nerve and van cause vertigo and dysequilibrium.
Twenty percent of small tumors are associated with
periodic vertigo, which is characterized by dizziness
or a whirling sensation. Larger acoustic neuromas are
less likely to cause vertigo but more likely to cause
dysequilibrium. Dysequilibrium, which is characterized by minor clumsiness and a general feeling of
instability, occurs in nearly 50% of people with an
acoustic neuroma.
As the tumor grows larger it can press on the
surrounding cranial nerves. Compression of the fifth
cranial nerve can result in facial pain and or numbness. Compression of the seventh cranial nerve can
cause spasms, weakness or paralysis of the facial
muscles. Double vision is a rare symptom but can
result when the 6th cranial nerve is affected.
Swallowing and/or speaking difficulties can occur if
the tumor presses against the 9th, 10th, or 12th cranial nerves.
If left untreated, the tumor can become large
enough to press against and affect the functioning
of the brain stem. The brain stem is the stalk like
portion of the brain that joins the spinal cord to the
cerebrum, the thinking and reasoning part of the
brain. Different parts of the brainstem have different
functions such as the control of breathing and muscle
coordination. Large tumors that impact the brain
stem can result in headaches, walking difficulties
(gait ataxia) and involuntary shaking movements of
the muscles (tremors). In rare cases when an acoustic
neuroma remains undiagnosed and untreated it can
cause nausea, vomiting, lethargy and eventually
coma, respiratory difficulties and death. In the vast
majority of cases, however, the tumor is discovered
and treated long before it is large enough to cause
such serious manifestations.
GALE ENCYCLOPEDIA OF MEDICINE

Anyone with symptoms of hearing loss should
undergo hearing evaluations. Pure tone and speech
audiometry are two screening tests that are often
used to evaluate hearing. Pure tone audiometry
tests to see how well someone can hear tones of
different volume and pitch and speech audiometry
tests to see how well someone can hear and recognize speech. An acoustic neuroma is suspected in
someone with unilateral hearing loss or hearing loss
that is less severe in one ear than the other ear
(asymmetrical).
Sometimes an auditory brainstem response (ABR,
BAER) test is performed to help establish whether
someone is likely to have an acoustic neuroma.
During the ABR examination, a harmless electrical
impulse is passed from the inner ear to the brainstem.
An acoustic neuroma can interfere with the passage of
this electrical impulse and this interference can, sometimes be identified through the ABR evaluation.
A normal ABR examination does not rule out the
possibility of an acoustic neuroma. An abnormal
ABR examination increases the likelihood that an
acoustic neuroma is present but other tests are necessary to confirm the presence of a tumor.
If an acoustic neuroma is strongly suspected then
magnetic resonance imaging (MRI) is usually performed. The MRI is a very accurate evaluation that
is able to detect nearly 100% of acoustic neuromas.
Computerized tomography (CT scan, CAT scan)is
unable to identify smaller tumors; but it can be used
when an acoustic neuroma is suspected and an MRI
evaluation cannot be performed.
Once an acoustic neuroma is diagnosed, an evaluation by genetic specialists such as a geneticist and
genetic counselor may be recommended. The purpose
of this evaluation is to obtain a detailed family history
and check for signs of NF2. If NF2 is strongly suspected then DNA testing may be recommended. DNA
testing involves checking the blood cells obtained from
a routine blood draw for the common gene changes
associated with NF2.

Treatment
The three treatment options for acoustic neuroma
are surgery, radiation, and observation. The physician
and patient should discuss the pros and cons of
the different options prior to making a decision
about treatment. The patient’s, physical health, age,
symptoms, tumor size, and tumor location should be
considered.
GALE ENCYCLOPEDIA OF MEDICINE

Microsurgery
The surgical removal of the tumor or tumors is the
most common treatment for acoustic neuroma. In
most cases the entire tumor is removed during the
surgery. If the tumor is large and causing significant
symptoms, yet there is a need to preserve hearing
in that ear, then only part of the tumor may be
removed. During the procedure the tumor is removed
under microscopic guidance and general anesthetic.
Monitoring of the neighboring cranial nerves is done
during the procedure so that damage to these nerves
can be prevented. If preservation of hearing is a possibility, then monitoring of hearing will also take place
during the surgery.
Most people stay in the hospital four to seven days
following the surgery. Total recovery usually takes
four to six weeks. Most people experience fatigue and
head discomfort following the surgery. Problems with
balance and head and neck stiffness are also common.
The mortality rate of this type of surgery is less than
2% at most major centers. Approximately 20% of
patients experience some degree of post-surgical complications. In most cases these complications can be
managed successfully and do not result in long term
medical problems. Surgery brings with it a risk of
stroke, damage to the brain stem, infection, leakage
of spinal fluid and damage to the cranial nerves.
Hearing loss and/or tinnitis often result from the surgery. A follow-up MRI is recommended one to five
years following the surgery because of possible
regrowth of the tumor.
Stereotactic radiation therapy
During stereotactic radiation therapy, also called
radiosurgery or radiotherapy, many small beams of
radiation are aimed directly at the acoustic neuroma.
The radiation is administered in a single large dose,
under local anesthetic and is performed on an outpatient basis. This results in a high dose of radiation
to the tumor but little radiation exposure to the
surrounding area. This treatment approach is limited
to small or medium tumors. The goal of the surgery is
to cause tumor shrinkage or at least limit the growth
of the tumor. The long-term efficacy and risks of this
treatment approach are not known; however, as of
the early 2000s, more and more patients diagnosed
with acoustic neuromas are choosing this form of
therapy. Periodic MRI monitoring throughout the
life of the patient is therefore recommended.
Radiation therapy can cause hearing loss which
can sometimes occurs even years later. Radiation therapy can also cause damage to neighboring cranial
31

Acoustic neuroma

Diagnosis

Acrocyanosis

nerves, which can result in symptoms such as numbness, pain or paralysis of the facial muscles. In many
cases these symptoms are temporary. Radiation treatment can also induce the formation of other benign or
malignant schwannomas. This type of treatment may
therefore be contraindicated in the treatment of acoustic neuromas in those with NF2 who are predisposed
to developing schwannomas and other tumors.
Observation
Acoustic neuromas are usually slow growing and
in some cases they will stop growing and even become
smaller or disappear entirely. It may therefore be
appropriate in some cases to hold off on treatment
and to periodically monitor the tumor through MRI
evaluations. Long-term observation may be appropriate for example in an elderly person with a small
acoustic neuroma and few symptoms. Periodic observation may also be indicated for someone with a small
and asymptomatic acoustic neuroma that was
detected through an evaluation for another medical
problem. Observation may also be suggested for someone with an acoustic neuroma in the only hearing ear
or in the ear that has better hearing. The danger of an
observational approach is that as the tumor grows
larger it can become more difficult to treat.

Prognosis
The prognosis for someone with a unilateral
acoustic neuroma is usually quite good provided the
tumor is diagnosed early and appropriate treatment is
instituted. Long term-hearing loss and tinnitis in the
affected ear are common, even if appropriate treatment is provided. Many patients also experience
facial weakness, balance problems, and headaches.
Regrowth of the tumor is also a possibility following
surgery or radiation therapy and repeat treatment may
be necessary. The prognosis can be poorer for those
with NF2 who have an increased risk of bilateral
acoustic neuromas and other tumors.

Kundi, M., K. Mild, L. Hardell, and M. O. Mattsson.
‘‘Mobile Telephones and Cancer—A Review of
Epidemiological Evidence.’’ Journal of Toxicology and
Environmental Health, Part B, Critical Reviews 7
(September-October 2004): 351–384.
Ryzenman, J. M., M. L. Pensak, and J. M. Tew, Jr. ‘‘Patient
Perception of Comorbid Conditions After Acoustic
Neuroma Management: Survey Results from the
Acoustic Neuroma Association.’’ Laryngoscope 114
(May 2004): 814–820.
ORGANIZATIONS

Acoustic Neuroma Association. 600 Peachtree Pkwy, Suite
108, Cumming, GA 30041-6899. (770) 205-8211. Fax:
(770) 205-0239. ANAusa@aol.com. [cited June 28,
2001]. <http://anausa.org>.
Acoustic Neuroma Association of Canada Box 369,
Edmonton, AB T5J 2J6. 1-800-561-ANAC(2622).
(780)428-3384. anac@compusmart.ab.ca. [cited June
28, 2001]. <http://www.anac.ca>.
Seattle Acoustic Neuroma Group. Emcityland@aol.com.
[cited June 28, 2001]. <http://acousticneuromaseattle.org/entryenglish.html>.
OTHER

National Institute of Health Consensus Statement Online.
Acoustic Neuroma 9, no. 4 (December 11-13, 1991).
[cited June 28, 2001]. <http://text.nlm.nih.gov/nih/cdc/
www/87txt.html>.
University of California at San Francisco (UCSF).
Information on Acoustic Neuromas. March 18, 1998.
[cited June 28, 2001]. <http://itsa.ucsf.edu/~rkj/
IndexAN.html>.

Lisa Andres, MS, CGC
Rebecca J. Frey, PhD

Acquired hypogammaglobulinemia see
Common variable immunodeficiency
Acquired immunodeficiency syndrome see
AIDS

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Acoustic Neuroma.’’ Section 7, Chapter 85 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2002.
PERIODICALS

Kondziolka, D., L. D. Lundsford, and J. C. Flickinger.
‘‘Acoustic Neuroma Radiosurgery. Origins,
Contemporary Use and Future Expectations.’’
Neurochirurgie 50 (June 2004): 427–435.

32

I Acrocyanosis
Definition
Acrocyanosis is a decrease in the amount of
oxygen delivered to the extremities. The hands and
feet turn blue because of the lack of oxygen.
Decreased blood supply to the affected areas is caused
by constriction or spasm of small blood vessels.

GALE ENCYCLOPEDIA OF MEDICINE

Acrocyanosis is a painless disorder caused by constriction or narrowing of small blood vessels in the
skin of affected patients. The spasm of the blood
vessels decreases the amount of blood that passes
through them, resulting in less blood being delivered
to the hands and feet. The hands may be the main area
affected. The affected areas turn blue and become cold
and sweaty. Localized swelling may also occur.
Emotion and cold temperatures can worsen the symptoms, while warmth can decrease symptoms. The disease is seen mainly in women and the effect of the
disorder is mainly cosmetic. People with the disease
tend to be uncomfortable, with sweaty, cold, bluish
colored hands and feet.

KEY TERMS
Sympathetic nerve—A nerve of the autonomic nervous system that regulates involuntary and automatic reactions, especially to stress.

Prognosis
Acrocyanosis is a benign and persistent disease.
The main concern of patients is cosmetic. Left
untreated, the disease does not worsen.
Resources
BOOKS

Causes and symptoms
The sympathetic nerves cause constriction or
spasms in the peripheral blood vessels that supply
blood to the extremities. The spasms are a contraction
of the muscles in the walls of the blood vessels. The
contraction decreases the internal diameter of the
blood vessels, thereby decreasing the amount of
blood flow through the affected area. The spasms
occur on a persistent basis, resulting in long term
reduction of blood supply to the hands and feet.
Sufficient blood still passes through the blood vessels
so that the tissue in the affected areas does not starve
for oxygen or die. Mainly, blood vessels near the surface of the skin are affected.

Diagnosis
Diagnosis is made by observation of the main
clinical symptoms, including persistently blue and
sweaty hands and/or feet and a lack of pain. Cooling
the hands increases the blueness, while warming the
hands decreases the blue color. The acrocyanosis
patient’s pulse is normal, which rules out obstructive
diseases. Raynaud’s disease differs from acrocyanosis
in that it causes white and red skin coloration phases,
not just bluish discoloration.

Treatment
Acrocyanosis usually isn’t treated. Drugs that
block the uptake of calcium (calcium channel blockers)
and alpha-one antagonists reduce the symptoms in
most cases. Drugs that dilate blood vessels are
only effective some of the time. Sweating from the
affected areas can be profuse and require treatment.
Surgery to cut the sympathetic nerves is performed
rarely.
GALE ENCYCLOPEDIA OF MEDICINE

Alexander, R. W., R. C. Schlant, and V. Fuster, editors. The
Heart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD

I Acromegaly and gigantism
Definition
Acromegaly is a disorder in which the abnormal release of a particular chemical from the pituitary gland in the brain causes increased growth in
bone and soft tissue, as well as a variety of other
disturbances throughout the body. This chemical
released from the pituitary gland is called growth
hormone (GH). The body’s ability to process and
use nutrients like fats and sugars is also altered. In
children whose bony growth plates have not closed,
the chemical changes of acromegaly result in
exceptional growth of long bones. This variant is
called gigantism, with the additional bone growth
causing unusual height. When the abnormality occurs
after bone growth stops, the disorder is called
acromegaly.

Description
Acromegaly is a relatively rare disorder, occurring
in approximately 50 out of every one million people
(50/1,000,000). Both men and women are affected.
Because the symptoms of acromegaly occur so gradually, diagnosis is often delayed. The majority of patients
are not identified until they are middle aged.
33

Acromegaly and gigantism

Description

Acromegaly and gigantism

KEY TERMS
Adenoma—A type of noncancerous (benign) tumor
that often involves the overgrowth of certain cells
found in glands.
Gland—A collection of cells that releases certain
chemicals, or hormones, that are important to the
functioning of other organs or body systems.
Hormone—A chemical produced in one part of the
body that travels to another part of the body in order
to exert an effect.
Hypothalamus—A structure within the brain
responsible for a large number of normal functions
throughout the body, including regulating sleep,
temperature, eating, and sexual development. The
hypothalamus also regulates the functions of the
pituitary gland by directing the pituitary to stop or
start production of its hormones.
Pituitary—A gland located at the base of the brain
that produces a number of hormones, including
those that regulate growth and reproductive functions. Overproduction of the pituitary hormone
called growth hormone (GH) is responsible for the
condition known as acromegaly.

Enlarged feet is one deformity caused by acromegaly.
(Custom Medical Stock Photo. Reproduced by permission.)

Causes and symptoms
The pituitary is a small gland located at the base of
the brain. A gland is a collection of cells that releases
certain chemicals, or hormones, which are important
to the functioning of other organs or body systems.
The pituitary hormones travel throughout the body
and are involved in a large number of activities,
including the regulation of growth and reproductive
functions. The cause of acromegaly can be traced to
the pituitary’s production of GH.
Under normal conditions, the pituitary receives
input from another brain structure, the hypothalamus,
located at the base of the brain. This input from the
hypothalamus regulates the pituitary’s release of hormones. For example, the hypothalamus produces
growth hormone-releasing hormone (GHRH), which
directs the pituitary to release GH. Input from the
hypothalamus should also direct the pituitary to stop
releasing hormones.
34

In acromegaly, the pituitary continues to release
GH and ignores signals from the hypothalamus. In the
liver, GH causes production of a hormone called insulin-like growth factor 1 (IGF-1), which is responsible
for growth throughout the body. When the pituitary
refuses to stop producing GH, the levels of IGF-1 also
reach abnormal peaks. Bones, soft tissue, and organs
throughout the body begin to enlarge, and the body
changes its ability to process and use nutrients like
sugars and fats.
In acromegaly, an individual’s hands and feet begin
to grow, becoming thick and doughy. The jaw line, nose,
and forehead also grow, and facial features are described
as ‘‘coarsening’’. The tongue grows larger, and because
the jaw is larger, the teeth become more widely spaced.
Due to swelling within the structures of the throat
and sinuses, the voice becomes deeper and sounds
more hollow, and patients may develop loud snoring.
Various hormonal changes cause symptoms such as:


heavy sweating



oily skin



increased coarse body hair



improper processing of sugars in the diet (and sometimes actual diabetes)
GALE ENCYCLOPEDIA OF MEDICINE

high blood pressure



increased calcium in the urine (sometimes leading to
kidney stones)



increased risk of gallstones; and



swelling of the thyroid gland

People with acromegaly have more skin tags, or
outgrowths of tissue, than normal. This increase in
skin tags is also associated with the development of
growths, called polyps, within the large intestine that
may eventually become cancerous. Patients with acromegaly often suffer from headaches and arthritis. The
various swellings and enlargements throughout the
body may press on nerves, causing sensations of local
tingling or burning, and sometimes result in muscle
weakness.
The most common cause of this disorder (in 90%
of patients) is the development of a noncancerous
tumor within the pituitary, called a pituitary adenoma.
These tumors are the source of the abnormal release of
GH. As these tumors grow, they may press on nearby
structures within the brain, causing headaches and
changes in vision. As the adenoma grows, it may disrupt other pituitary tissue, interfering with the release
of other hormones. These disruptions may be responsible for changes in the menstrual cycle of women,
decreases in the sexual drive in men and women, and
the abnormal production of breast milk in women.
In rare cases, acromegaly is caused by the abnormal
production of GHRH, which leads to the increased
production of GH. Certain tumors in the pancreas,
lungs, adrenal glands, thyroid, and intestine produce
GHRH, which in turn triggers production of an
abnormal quantity of GH.

Diagnosis
Because acromegaly produces slow changes over
time, diagnosis is often significantly delayed. In fact,
the characteristic coarsening of the facial features is
often not recognized by family members, friends, or
long-time family physicians. Often, the diagnosis is
suspected by a new physician who sees the patient for
the first time and is struck by the patient’s characteristic facial appearance. Comparing old photographs
from a number of different time periods will often
increase suspicion of the disease.
Because the quantity of GH produced varies
widely under normal conditions, demonstrating high
levels of GH in the blood is not sufficient to merit a
diagnosis of acromegaly. Instead, laboratory tests measuring an increase of IGF-1 (3-10 times above the
normal level) are useful. These results, however, must
GALE ENCYCLOPEDIA OF MEDICINE

Acromegaly and gigantism



A comparison of the right hand of a person afflicted
with acromegaly (left) and the hand of a normal sized person.
(Custom Medical Stock Photo. Reproduced by permission.)

be carefully interpreted because normal laboratory
values for IGF-1 vary when the patient is pregnant,
undergoing puberty, elderly, or severely malnourished.
Normal patients will show a decrease in GH production when given a large dose of sugar (glucose). Patients
with acromegaly will not show this decrease, and will
often show an increase in GH production. Magnetic
resonance imaging (MRI) is useful for viewing the
pituitary, and for identifying and locating an adenoma.
When no adenoma can be located, the search for a
GHRH-producing tumor in another location begins.

Treatment
The first step in treatment of acromegaly is
removal of all or part of the pituitary adenoma.
Removal requires surgery, usually performed by
entering the skull through the nose. While this surgery
can cause rapid improvement of many acromegaly
symptoms, most patients will also require additional
treatment with medication. Bromocriptine (Parlodel)
is a medication that can be taken by mouth, while
octreotide (Sandostatin) must be injected every eight
hours. Both of these medications are helpful in reducing GH production, but must often be taken for life
and produce their own unique side effects. Some
patients who cannot undergo surgery are treated
with radiation therapy to the pituitary in an attempt
to shrink the adenoma. Radiating the pituitary may
take up to 10 years, however, and may also injure/
destroy other normal parts of the pituitary.

Prognosis
Without treatment, patients with acromegaly will
most likely die early because of the disease’s effects on
35

Actinomycosis

the heart, lungs, brain, or due to the development of
cancer in the large intestine. With treatment, however,
a patient with acromegaly may be able to live a normal
lifespan.
Resources
BOOKS

Biller, Beverly M. K., and Gilbert H. Daniels. ‘‘Growth
Hormone Excess: Acromegaly and Gigantism.’’ In
Harrison’s Principles of Internal Medicine, edited by
Anthony S. Fauci, et al. New York: McGraw-Hill,
1997.

Biopsy—The process that removes a sample of tissue for microscopic examination to aid in the diagnosis of a disease.
Sinus tract—A narrow, elongated channel in the
body that allows the escape of fluid.

Causes and symptoms

ORGANIZATIONS

Pituitary Tumor Network Association. 16350 Ventura
Blvd., #231, Encino, CA 91436. (805) 499-9973.

Rosalyn Carson-DeWitt, MD

ACT see Alanine aminotransferase test
ACTH test see Adrenocorticotropic
hormone test
Actinomyces israelii infection see
Actinomycosis

I Actinomycosis
Definition
Actinomycosis is an infection primarily caused by
the bacterium Actinomyces israelii. Infection most
often occurs in the face and neck region and is characterized by the presence of a slowly enlarging, hard,
red lump.

Description
Actinomycosis is a relatively rare infection
occurring in one out of 300,000(1/300,000) people
per year. It is characterized by the presence of a
lump or mass that often forms, draining sinus tracts
to the skin surface. Fifty percent of actinomycosis
cases are of the head and neck region (also called
‘‘lumpy jaw’’ and ‘‘cervicofacial actinomycosis’’),
15% are in the chest, 20% are in the abdomen, and
the rest are in the pelvis, heart, and brain. Men are
three times more likely to develop actinomycosis than
women.

36

KEY TERMS

Actinomycosis is usually caused by the bacterium
Actinomyces israelii. This bacterium is normally present in the mouth but can cause disease if it enters
tissues following an injury. Actinomyces israelii is an
anaerobic bacterium which means it dislikes oxygen
but grows very well in deep tissues where oxygen levels
are low. Tooth extraction, tooth disease, root canal
treatment, jaw surgery, or poor dental hygiene can
allow Actinomyces israelii to cause an infection in the
head and neck region.
The main symptom of cervicofacial actinomycosis
is the presence of a hard lump on the face or neck. The
lump may or may not be red. Fever occurs in some
cases.

Diagnosis
Cervicofacial actinomycosis can be diagnosed by
a family doctor or dentist and the patient may be
referred to an oral surgeon or infectious disease
specialist. The diagnosis of actinomycosis is based
upon several things. The presence of a red lump with
draining sinuses on the head or neck is strongly
suggestive of cervicofacial actinomycosis. A recent
history of tooth extraction or signs of tooth decay or
poor dental hygiene aid in the diagnosis. Microscopic
examination of the fluid draining from the sinuses
shows the characteristic ‘‘sulfur Granules’’ (small
yellow colored material in the fluid) produced by
Actinomyces israelii. A biopsy may be performed to
remove a sample of the infected tissue. This procedure
can be performed under local anesthesia in the doctor’s
office. Occasionally the bacteria can be cultured
from the sinus tract fluid or from samples of the
infected tissue.
Actinomycosis in the lungs, abdomen, pelvis, or
brain can be very hard to diagnose since the symptoms
often mimic those of other diseases. Actinomycosis

GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Actinomycosis is difficult to treat because of its
dense tissue location. Surgery is often required to
drain the lesion and/or to remove the site of infection. To kill the bacteria, standard therapy has
included large doses of penicillin given through a
vein daily for two to six weeks followed by six to
twelve months of penicillin taken by mouth.
Tetracycline, clindamycin, or erythromycin may be
used instead of penicillin. The antibiotic therapy
must be completed to ensure that the infection
does not return. However, a report in 2004 on
several cases of actinomycosis said that therapy
depends on the individual case and that many
patients today will be diagnosed in earlier stages
of the disease. Sometimes, shorter courses of antibiotic treatment are effective, with close diagnostic
x-ray monitoring. Hyperbaric oxygen (oxygen
under high pressure) therapy in combination with
the antibiotic therapy has been successful.

Prognosis
Complete recovery is achieved following treatment. If left untreated, the infection may cause localized bone destruction.

I Acupressure
Definition
Acupressure is a form of touch therapy that
utilizes the principles of acupuncture and Chinese
medicine. In acupressure, the same points on the
body are used as in acupuncture, but are stimulated
with finger pressure instead of with the insertion of
needles. Acupressure is used to relieve a variety of
symptoms and pain.

Purpose
Acupressure massage performed by a therapist
can be very effective both as prevention and as a
treatment for many health conditions, including
headaches, general aches and pains, colds and flu,
arthritis, allergies, asthma, nervous tension, menstrual cramps, sinus problems, sprains, tennis elbow,
and toothaches, among others. Unlike acupuncture
which requires a visit to a professional, acupressure
can be performed by a layperson. Acupressure techniques are fairly easy to learn, and have been used to
provide quick, cost-free, and effective relief from
many symptoms. Acupressure points can also be
stimulated to increase energy and feelings of wellbeing, reduce stress, stimulate the immune system,
and alleviate sexual dysfunction.

Description
Origins

Prevention
The best prevention is to maintain good dental
hygiene.
Resources
PERIODICALS

Sudhaker, Selvin S., and John J. Rose. ‘‘Short-term
Treatment of Actinomycosis: two Cases and a
Review.’’ Clinical Infectious Diseases (February 1,
2004): 444–448.

Belinda Rowland, PhD
Teresa G. Odle

Activated charcoal see Charcoal, activated
Activated partial thromboplastin time see
Partial thromboplastin time
GALE ENCYCLOPEDIA OF MEDICINE

One of the oldest text of Chinese medicine is the
Huang Di, The Yellow Emperor’s Classic of Internal
Medicine, which may be at least 2,000 years old.
Chinese medicine has developed acupuncture, acupressure, herbal remedies, diet, exercise, lifestyle changes,
and other remedies as part of its healing methods.
Nearly all of the forms of Oriental medicine that are
used in the West today, including acupuncture, acupressure, shiatsu, and Chinese herbal medicine, have
their roots in Chinese medicine. One legend has it that
acupuncture and acupressure evolved as early Chinese
healers studied the puncture wounds of Chinese warriors, noting that certain points on the body created
interesting results when stimulated. The oldest known
text specifically on acupuncture points, the Systematic
Classic of Acupuncture, dates back to 282 A.D.
Acupressure is the non-invasive form of acupuncture,
as Chinese physicians determined that stimulating
points on the body with massage and pressure could
be effective for treating certain problems.
37

Acupressure

of the lungs or abdomen can resemble tuberculosis
or cancer. Diagnostic x-ray results, the presence of
draining sinus tracts, and microscopic analysis
and culturing of infected tissue assist in the diagnosis.

Acupressure
Therapist working acupressure points on a woman’s shoulder. (Photo Researchers, Inc. Reproduced by permission.)

Outside of Asian-American communities, Chinese
medicine remained virtually unknown in the United
States until the 1970s, when Richard Nixon became
the first U.S. president to visit China. On Nixon’s trip,
journalists were amazed to observe major operations
being performed on patients without the use of anesthetics. Instead, wide-awake patients were being operated on, with only acupuncture needles inserted into
them to control pain. At that time, a famous columnist
for the New York Times, James Reston, had to
undergo surgery and elected to use acupuncture for
anesthesia. Later, he wrote some convincing stories
on its effectiveness. Despite being neglected by
mainstream medicine and the American Medical
Association (AMA), acupuncture and Chinese medicine became a central to alternative medicine practitioners in the United States. Today, there are millions
of patients who attest to its effectiveness, and nearly
9,000 practitioners in all 50 states.
Acupressure is practiced as a treatment by Chinese
medicine practitioners and acupuncturists, as well as
by massage therapists. Most massage schools in
American include acupressure techniques as part of
38

their bodywork programs. Shiatsu massage is very
closely related to acupressure, working with the same
points on the body and the same general principles,
although it was developed over centuries in Japan
rather than in China. Reflexology is a form of bodywork based on acupressure concepts. Jin Shin Do is a
bodywork technique with an increasing number of
practitioners in America that combines acupressure
and shiatsu principles with qigong, Reichian theory,
and meditation.
Acupressure and Chinese medicine
Chinese medicine views the body as a small part
of the universe, subject to laws and principles of
harmony and balance. Chinese medicine does not
make as sharp a destinction as Western medicine
does between mind and body. The Chinese system
believes that emotions and mental states are every
bit as influential on disease as purely physical
mechanisms, and considers factors like work, environment, and relationships as fundamental to a
patient’s health. Chinese medicine also uses very different symbols and ideas to discuss the body and
GALE ENCYCLOPEDIA OF MEDICINE

Acupoint—A pressure
acupressure.
Chi—Basic life energy.

point

stimulated

in

Meridian—A channel through which chi travels in
the body.
Moxibustion—An acupuncture technique that
burns the herb moxa or mugwort.
Shiatsu—Japanese form of acupressure massage.
Yin/yang—Universal characteristics
describe aspects of the natural world.

used

to

Governing vessel 24.5

health. While Western medicine typically describes
health as mainly physical processes composed of chemical equations and reactions, the Chinese use ideas
like yin and yang, chi, and the organ system to
describe health and the body.

Lung 10

I

II
If/
I

I
I

Stomach 36

GALE ENCYCLOPEDIA OF MEDICINE

Everything in the universe has properties of
yin and yang. Yin is associated with cold, female,
passive, downward, inward, dark, wet. Yang can be
described as hot, male, active, upward, outward, light,
dry, and so on. Nothing is either completely yin or
yang. These two principles always interact and affect
each other, although the body and its organs can
become imbalanced by having either too much or too
little of either.
Chi (pronounced chee, also spelled qi or ki in
Japanese shiatsu) is the fundamental life energy. It is
found in food, air, water, and sunlight, and it travels
through the body in channels called meridians. There
are 12 major meridians in the body that transport chi,
corresponding to the 12 main organs categorized by
Chinese medicine.
Disease is viewed as an imbalance of the organs
and chi in the body. Chinese medicine has developed
intricate systems of how organs are related to physical
and mental symptoms, and it has devised corresponding treatments using the meridian and pressure point
networks that are classified and numbered. The goal

Press on point governing vessel 24.5, the top of the bridge of
the nose, lightly for two minutes to relieve hay fever symptoms.
Press on lung 10, the center of the thumb pad, for one minute to
alleviate a sore throat. To ease heartburn, apply pressure to
stomach 36, four finger-widths below the kneecap outside the
shinbone. Use on both legs. (Illustration by Electronic Illustrators
Group.)

39

Acupressure

KEY TERMS

Acupressure

of acupressure, and acupuncture, is to stimulate and
unblock the circulation of chi, by activating very specific points, called pressure points or acupoints.
Acupressure seeks to stimulate the points on the chi
meridians that pass close to the skin, as these are
easiest to unblock and manipulate with finger
pressure.
Acupressure can be used as part of a Chinese
physician’s prescription, as a session of massage therapy, or as a self-treatment for common aches and illnesses. A Chinese medicine practitioner examines a
patient very thoroughly, looking at physical, mental
and emotional activity, taking the pulse usually at the
wrists, examining the tongue and complexion, and
observing the patient’s demeanor and attitude, to get
a complete diagnosis of which organs and meridian
points are out of balance. When the imbalance is
located, the physician will recommend specific pressure points for acupuncture or acupressure. If acupressure is recommended, the patient might opt for a series
of treatments from a massage therapist.
In massage therapy, acupressurists will evaluate a
patient’s symptoms and overall health, but a massage
therapist’s diagnostic training isn’t as extensive as a
Chinese physician’s. In a massage therapy treatment, a
person usually lies down on a table or mat, with thin
clothing on. The acupressurist will gently feel and
palpate the abdomen and other parts of the body to
determine energy imbalances. Then, the therapist will
work with different meridians throughout the body,
depending on which organs are imbalanced in the
abdomen. The therapist will use different types of
finger movements and pressure on different acupoints,
depending on whether the chi needs to be increased
or dispersed at different points. The therapist observes
and guides the energy flow through the patient’s body
throughout the session. Sometimes, special herbs
(Artemesia vulgaris or moxa) may be placed on a
point to warm it, a process called moxibustion. A session of acupressure is generally a very pleasant experience, and some people experience great benefit
immediately. For more chronic conditions, several
sessions may be necessary to relieve and improve
conditions.
Acupressure massage usually costs from $30–70
per hour session. A visit to a Chinese medicine physician or acupuncturist can be more expensive, comparable to a visit to an allopathic physician if the
practitioner is an MD. Insurance reimbursement varies widely, and consumers should be aware if their
policies cover alternative treatment, acupuncture, or
massage therapy.

40

Self-treatment
Acupressure is easy to learn, and there are many
good books that illustrate the position of acupoints
and meridians on the body. It is also very versatile, as
it can be done anywhere, and it’s a good form of
treatment for spouses and partners to give to each
other and for parents to perform on children for
minor conditions.
While giving self-treatment or performing acupressure on another, a mental attitude of calmness
and attention is important, as one person’s energy
can be used to help another’s. Loose, thin clothing is
recommended. There are three general techniques for
stimulating a pressure point.


Tonifying is meant to strengthen weak chi, and is
done by pressing the thumb or finger into an acupoint with a firm, steady pressure, holding it for up to
two minutes.



Dispersing is meant to move stagnant or blocked
chi, and the finger or thumb is moved in a circular
motion or slightly in and out of the point for two
minutes.



Calming the chi in a pressure point utilizes the palm
to cover the point and gently stroke the area for
about two minutes.

There are many pressure points that are easily
found and memorized to treat common ailments
from headaches to colds.


For headaches, toothaches, sinus problems, and
pain in the upper body, the ‘‘LI4’’ point is recommended. It is located in the web between the thumb
and index finger, on the back of the hand. Using the
thumb and index finger of the other hand, apply a
pinching pressure until the point is felt, and hold it
for two minutes. Pregnant women should never
press this point.



To calm the nerves and stimulate digestion, find the
‘‘CV12’’ point that is four thumb widths above the
navel in the center of the abdomen. Calm the point
with the palm, using gentle stroking for several
minutes.



To stimulate the immune system, find the ‘‘TH5’’
point on the back of the forearm two thumb widths
above the wrist. Use a dispersing technique, or circular pressure with the thumb or finger, for two
minutes on each arm.



For headaches, sinus congestion, and tension, locate
the ‘‘GB20’’ points at the base of the skull in the
back of the head, just behind the bones in back of

GALE ENCYCLOPEDIA OF MEDICINE

Resources

Acupuncture

the ears. Disperse these points for two minutes with
the fingers or thumbs. Also find the ‘‘yintang’’ point,
which is in the middle of the forehead between the
eyebrows. Disperse it with gentle pressure for two
minutes to clear the mind and to relieve headaches.

PERIODICALS

Massage Therapy Journal. 820 Davis Street, Suite100,
Evanston, IL 60201-4444.
OTHER

Precautions
Acupressure is a safe technique, but it is not meant
to replace professional health care. A physician should
always be consulted when there are doubts about
medical conditions. If a condition is chronic, a professional should be consulted; purely symptomatic treatment can exacerbate chronic conditions. Acupressure
should not be applied to open wounds, or where there
is swelling and inflammation. Areas of scar tissue,
blisters, boils, rashes, or varicose veins should be
avoided. Finally, certain acupressure points should
not be stimulated on people with high or low blood
pressure and on pregnant women.

Research and general acceptance
In general, Chinese medicine has been slow to
gain acceptance in the West, mainly because it rests
on ideas very foreign to the scientific model. For
instance, Western scientists have trouble with the
idea of chi, the invisible energy of the body, and the
idea that pressing on certain points can alleviate
certain conditions seems sometimes too simple for
scientists to believe.
Western scientists, in trying to account for the
action of acupressure, have theorized that chi is actually part of the neuroendocrine system of the body.
Celebrated orthopedic surgeon Robert O. Becker,
who was twice nominated for the Nobel Prize, wrote
a book on the subject called Cross Currents: The
Promise of Electromedicine; The Perils of Electropollution. By using precise electrical measuring
devices, Becker and his colleagues showed that the
body has a complex web of electromagnetic energy,
and that traditional acupressure meridians and points
contained amounts of energy that non-acupressure
points did not.
The mechanisms of acupuncture and acupressure remain difficult to document in terms of the
biochemical processes involved; numerous testimonials are the primary evidence backing up the
effectiveness of acupressure and acupuncture.
However, a body of research is growing that verifies the effectiveness in acupressure and acupuncture techniques in treating many problems and in
controlling pain.

GALE ENCYCLOPEDIA OF MEDICINE

American Association of Oriental Medicine.December 28,
2000. <http://www.aaom.org>.
National Acupuncture and Oriental Medicine Alliance.
December 28, 2000. <http://www.acuall.org>.

Douglas Dupler, MA

Acupressure, foot see Reflexology

I Acupuncture
Definition
Acupuncture is one of the main forms of treatment in traditional Chinese medicine. It involves the
use of sharp, thin needles that are inserted in the body
at very specific points. This process is believed to
adjust and alter the body’s energy flow into healthier
patterns, and is used to treat a wide variety of illnesses
and health conditions.

Purpose
The World Health Organization (WHO) recommends acupuncture as an effective treatment for over
forty medical problems, including allergies, respiratory conditions, gastrointestinal disorders, gynecological problems, nervous conditions, and disorders of
the eyes, nose and throat, and childhood illnesses,
among others. Acupuncture has been used in the
treatment of alcoholism and substance abuse. It is
an effective and low-cost treatment for headaches
and chronic pain, associated with problems like
back injuries and arthritis. It has also been used
to supplement invasive Western treatments like
chemotherapy and surgery. Acupuncture is generally
most effective when used as prevention or before a
health condition becomes acute, but it has been used
to help patients suffering from cancer and AIDS.
Acupuncture is limited in treating conditions or
traumas that require surgery or emergency care
(such as for broken bones).
41

Acupuncture
Woman undergoing facial acupuncture. (Photograph by Yoav Levy. Phototake NYC. Reproduced by permission.)

Description
Origins
The original text of Chinese medicine is the Nei
Ching, The Yellow Emperor’s Classic of Internal
Medicine, which is estimated to be at least 2,500 years
old. Thousands of books since then have been written
on the subject of Chinese healing, and its basic philosophies spread long ago to other Asian civilizations.
Nearly all of the forms of Oriental medicine which are
used in the West today, including acupuncture, shiatsu,
acupressure massage, and macrobiotics, are part of or
have their roots in Chinese medicine. Legend has it that
acupuncture developed when early Chinese physicians
observed unpredicted effects of puncture wounds in
Chinese warriors. The oldest known text on acupuncture, the Systematic Classic of Acupuncture, dates back
to 282 A.D. Although acupuncture is its best known
technique, Chinese medicine traditionally utilizes herbal remedies, dietary therapy, lifestyle changes and
other means to treat patients.
In the early 1900s, only a few Western physicians
who had visited China were fascinated by acupuncture,
42

but outside of Asian-American communities it
remained virtually unknown until the 1970s, when
Richard Nixon became the first U.S. president to
visit China. On Nixon’s trip, journalists were amazed
to observe major operations being performed on
patients without the use of anesthetics. Instead,
wide-awake patients were being operated on with
only acupuncture needles inserted into them to control pain. During that time, a famous columnist for
the New York Times, James Reston, had to undergo
surgery and elected to use acupuncture instead of
pain medication, and he wrote some convincing
stories on its effectiveness.
Today, acupuncture is being practiced in all 50
states by over 9,000 practitioners, with over 4,000
MDs including it in their practices. Acupuncture has
shown notable success in treating many conditions,
and over 15 million Americans have used it as a therapy. Acupuncture, however, remains largely unsupported by the medical establishment. The American
Medical Association has been resistant to researching
it, as it is based on concepts very different from the
Western scientific model.
GALE ENCYCLOPEDIA OF MEDICINE

Acupuncture

Governor vessel
Bladder meridian
Triple burner meridian
Conception vessel
Stomach meridian
Large intestine meridian
Small intestine meridian
Gallbladder meridian

Acupuncture sites and meridians on the face and neck. (Illustration by Hans & Cassady.)

KEY TERMS
Acupressure—Form of massage using acupuncture
points.
Auricular acupuncture—Acupuncture using only
points found on the ears.
Chi—Basic life energy.
Meridian—Channel through which chi travels in
the body.
Moxibustion—Acupuncture technique which
burns the herb moxa or mugwort.
Tonification—Acupuncture technique for strengthening the body.
Yin/Yang—Universal characteristics
describe aspects of the natural world.

used

to

Several forms of acupuncture are being used
today in America. Japanese acupuncture uses extremely thin needles and does not incorporate herbal
medicine in its practice. Auricular acupuncture uses
acupuncture points only on the ear, which are
GALE ENCYCLOPEDIA OF MEDICINE

believed to stimulate and balance internal organs.
In France, where acupuncture is very popular and
more accepted by the medical establishment, neurologist Paul Nogier developed a system of acupuncture
based on neuroendocrine theory rather than on traditional Chinese concepts, which is gaining some use
in America.
Basic ideas of Chinese medicine
Chinese medicine views the body as a small part
of the universe, and subject to universal laws and
principles of harmony and balance. Chinese medicine
does not draw a sharp line, as Western medicine does,
between mind and body. The Chinese system believes
that emotions and mental states are every bit as
influential on disease as purely physical mechanisms,
and considers factors like work, environment, lifestyle and relationships as fundamental to the overall
picture of a patient’s health. Chinese medicine also
uses very different symbols and ideas to discuss the
body and health. While Western medicine typically
describes health in terms of measurable physical
processes made up of chemical reactions, the Chinese
use ideas like yin and yang, chi, the organ system, and
43

Acupuncture

the five elements to describe health and the body. To
understand the ideas behind acupuncture, it is worthwhile to introduce some of these basic terms.
YIN AND YANG. According to Chinese philosophy,
the universe and the body can be described by two
separate but complementary principles, that of yin
and yang. For example, in temperature, yin is cold
and yang is hot. In gender, yin is female and yang is
male. In activity, yin is passive and yang is active. In
light, yin is dark and yang is bright; in direction yin is
inward and downward and yang is outward and up,
and so on. Nothing is ever completely yin or yang, but
a combination of the two. These two principles are
always interacting, opposing, and influencing each
other. The goal of Chinese medicine is not to eliminate
either yin or yang, but to allow the two to balance each
other and exist harmoniously together. For instance, if
a person suffers from symptoms of high blood pressure,
the Chinese system would say that the heart organ
might have too much yang, and would recommend
methods either to reduce the yang or to increase the
yin of the heart, depending on the other symptoms and
organs in the body. Thus, acupuncture therapies seek to
either increase or reduce yang, or increase or reduce yin
in particular regions of the body.
CHI. Another fundamental concept of Chinese
medicine is that of chi (pronounced chee, also spelled
qi). Chi is the fundamental life energy of the universe.
It is invisible and is found in the environment in the
air, water, food and sunlight. In the body, it is the
invisible vital force that creates and animates life.
We are all born with inherited amounts of chi, and
we also get acquired chi from the food we eat and the
air we breathe. The level and quality of a person’s chi
also depends on the state of physical, mental and
emotional balance. Chi travels through the body
along channels called meridians.
THE ORGAN SYSTEM. In the Chinese system, there
are twelve main organs: the lung, large intestine, stomach, spleen, heart, small intestine, urinary bladder,
kidney, liver, gallbladder, pericardium, and the ‘‘triple
warmer,’’ which represents the entire torso region.
Each organ has chi energy associated with it, and
each organ interacts with particular emotions on the
mental level. As there are twelve organs, there are
twelve types of chi which can move through the body,
and these move through twelve main channels or meridians. Chinese doctors connect symptoms to organs.
That is, symptoms are caused by yin/yang imbalances
in one or more organs, or by an unhealthy flow of chi
to or from one organ to another. Each organ has a
different profile of symptoms it can manifest.

44

THE FIVE ELEMENTS. Another basis of Chinese theory is that the world and body are made up of five
main elements: wood, fire, earth, metal, and water.
These elements are all interconnected, and each element either generates or controls another element. For
instance, water controls fire and earth generates metal.
Each organ is associated with one of the five elements.
The Chinese system uses elements and organs to
describe and treat conditions. For instance, the kidney
is associated with water and the heart is associated
with fire, and the two organs are related as water and
fire are related. If the kidney is weak, then there might
be a corresponding fire problem in the heart, so treatment might be made by acupuncture or herbs to cool
the heart system and/or increase energy in the kidney
system.

The Chinese have developed an intricate system of
how organs and elements are related to physical and
mental symptoms, and the above example is a very
simple one. Although this system sounds suspect to
Western scientists, some interesting parallels have
been observed. For instance, Western medicine has
observed that with severe heart problems, kidney failure often follows, but it still does not know exactly
why. In Chinese medicine, this connection between the
two organs has long been established.
MEDICAL PROBLEMS AND ACUPUNCTURE. In
Chinese medicine, disease as seen as imbalances in
the organ system or chi meridians, and the goal of
any remedy or treatment is to assist the body in reestablishing its innate harmony. Disease can be caused
by internal factors like emotions, external factors like
the environment and weather, and other factors like
injuries, trauma, diet, and germs. However, infection
is seen not as primarily a problem with germs and
viruses, but as a weakness in the energy of the body
which is allowing a sickness to occur. In Chinese medicine, no two illnesses are ever the same, as each body
has its own characteristics of symptoms and balance.
Acupuncture is used to open or adjust the flow of chi
throughout the organ system, which will strengthen
the body and prompt it to heal itself.
A VISIT TO THE ACUPUNCTURIST. The first thing
an acupuncturist will do is get a thorough idea of a
patient’s medical history and symptoms, both physical and emotional. This is done with a long questionnaire and interview. Then the acupuncturist will
examine the patient to find further symptoms, looking closely at the tongue, the pulse at various points
in the body, the complexion, general behavior,
and other signs like coughs or pains. From this, the
practitioner will be able to determine patterns of

GALE ENCYCLOPEDIA OF MEDICINE

Acupuncture needles are always sterilized and
acupuncture is a very safe procedure. The depth of
insertion of needles varies, depending on which chi
channels are being treated. Some points barely go
beyond superficial layers of skin, while some acupuncture points require a depth of 1-3 in (2.5-7.5 cm) of
needle. The needles generally do not cause pain.
Patients sometimes report pinching sensations and
often pleasant sensations, as the body experiences
healing. Depending on the problem, the acupuncturist
might spin or move the needles, or even pass a slight
electrical current through some of them. Moxibustion
may be sometimes used, in which an herbal mixture
(moxa or mugwort) is either burned like incense on the
acupuncture point or on the end of the needle, which
is believed to stimulate chi in a particular way. Also,
acupuncturists sometimes use cupping, during which
small suction cups are placed on meridian points to
stimulate them.
How long the needles are inserted also varies.
Some patients only require a quick in and out insertion to clear problems and provide tonification
(strengthening of health), while some other conditions might require needles inserted up to an hour or
more. The average visit to an acupuncturist takes
about thirty minutes. The number of visits to the
acupuncturist varies as well, with some conditions
improved in one or two sessions and others requiring
a series of six or more visits over the course of weeks
or months.
Costs for acupuncture can vary, depending
on whether the practitioner is an MD. Initial visits
with non-MD acupuncturists can run from $50$100, with follow-up visits usually costing less.
Insurance reimbursement also varies widely, depending on the company and state. Regulations have been
changing often. Some states authorize Medicaid to
cover acupuncture for certain conditions, and some
states have mandated that general coverage pay
for acupuncture. Consumers should be aware of
the provisions for acupuncture in their individual
policies.

GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Acupuncture is generally a very safe procedure. If
a patient is in doubt about a medical condition, more
than one physician should be consulted. Also, a
patient should always feel comfortable and confident
that their acupuncturist is knowledgable and properly
trained.

Research and general acceptance
Mainstream medicine has been slow to accept
acupuncture; although more MDs are using it, the
American Medical Association does not recognize
it as a specialty. The reason for this is that the
mechanism of acupuncture is difficult to scientifically understand or measure, such as the invisible
energy of chi in the body. Western medicine,
admitting that acupuncture works in many cases,
has theorized that the energy meridians are actually part of the nervous system and that acupuncture relieves pain by releasing endorphins, or
natural pain killers, into the bloodstream. Despite
the ambiguity in the biochemistry involved, acupuncture continues to show effectiveness in clinical
tests, from reducing pain to alleviating the symptoms of chronic illnesses, and research in acupuncture is currently growing. The Office of Alternative
Medicine of the National Institute of Health is
currently funding research in the use of acupuncture for treating depression and attention-deficit
disorder.
Resources
PERIODICALS

American Journal of Acupuncture. 1840 41st Ave., Suite 102,
P.O. Box 610, Capitola, CA 95010.
OTHER

American Association of Oriental Medicine. December 28,
2000. <http://www.aaom.org>.
North American Society of Acupuncture and Alternative
Medicine. December 28, 2000. <http://www.
nasa-altmed.com>.

Douglas Dupler, MA

Acute glomerulonephritis see Acute poststreptococcal glomerulonephritis
Acute homeopathic remedies see
Homeopathic remedies, acute prescribing
45

Acupuncture

symptoms which indicate which organs and areas
are imbalanced. Depending on the problem, the acupuncturist will insert needles to manipulate chi on
one or more of the twelve organ meridians. On these
twelve meridians, there are nearly 2,000 points which
can be used in acupuncture, with around 200 points
being most frequently used by traditional acupuncturists. During an individual treatment, one to
twenty needles may be used, depending on which
meridian points are chosen.

Acute kidney failure

I Acute kidney failure

KEY TERMS

Definition

Blood urea nitrogen (BUN)—A waste product that
is formed in the liver and collects in the bloodstream; patients with kidney failure have high
BUN levels.
Creatinine—A protein produced by muscle that
healthy kidneys filter out.

Acute kidney failure occurs when illness, infection, or injury damages the kidneys. Temporarily, the
kidneys cannot adequately remove fluids and wastes
from the body or maintain the proper level of certain
kidney-regulated chemicals in the bloodstream.

Extracorporeal—Outside of, or unrelated to, the
body.

Description
The kidneys are the body’s natural filtration
system. They perform the critical task of processing approximately 200 quarts of fluid in the
bloodstream every 24 hours. Waste products like
urea and toxins, along with excess fluids, are
removed from the bloodstream in the form of
urine. Kidney (or renal) failure occurs when kidney
functioning becomes impaired. Fluids and toxins
begin to accumulate in the bloodstream. As fluids
build up in the bloodstream, the patient with acute
kidney failure may become puffy and swollen (edematous) in the face, hands, and feet. Their blood
pressure typically begins to rise, and they may
experience fatigue and nausea.
Unlike chronic kidney failure, which is long
term and irreversible, acute kidney failure is a
temporary condition. With proper and timely treatment, it can typically be reversed. Often there is no
permanent damage to the kidneys. Acute kidney
failure appears most frequently as a complication
of serious illness, like heart failure, liver failure,
dehydration, severe burns, and excessive bleeding
(hemorrhage). It may also be caused by an
obstruction to the urinary tract or as a direct result
of kidney disease, injury, or an adverse reaction to
a medicine.

Causes and symptoms
Acute kidney failure can be caused by many different illnesses, injuries, and infections. These conditions
fall into three main categories: prerenal, postrenal, and
intrarenal conditions.
Prerenal conditions do not damage the kidney,
but can cause diminished kidney function. They are
the most common cause of acute renal failure, and
include:


dehydration



hemorrhage



septicemia, or sepsis

46

Ischemia—A lack of blood supply to an organ or
tissue.
Nephrotoxic—Toxic, or damaging, to the kidney.
Radiocontrast agents—Dyes administered to a
patient for the purposes of a radiologic study.
Sepsis—A bacterial infection of the bloodstream.
Vasopressors—Medications that constrict the
blood vessels.



heart failure



liver failure



burns

Postrenal conditions cause kidney failure by
obstructing the urinary tract. These conditions
include:


inflammation of the prostate gland in men
(prostatitis)



enlargement of the prostate gland (benign prostatic
hypertrophy)



bladder or pelvic tumors



kidney stones (calculi)

Intrarenal conditions involve kidney disease
or direct injury to the kidneys. These conditions
include:


lack of blood supply to the kidneys (ischemia)



use of radiocontrast agents in patients with kidney
problems



drug abuse or overdose



long-term use of nephrotoxic medications, like certain pain medicines



acute inflammation of the glomeruli, or filters, of the
kidney (glomerulonephritis)



kidney infections (pyelitis or pyelonephritis).
GALE ENCYCLOPEDIA OF MEDICINE



anemia. The kidneys are responsible for producing
erythropoietin (EPO), a hormone that stimulates red
blood cell production. If kidney disease causes
shrinking of the kidney, red blood cell production is
reduced, leading to anemia.



bad breath or bad taste in mouth. Urea in the saliva
may cause an ammonia-like taste in the mouth.



bone and joint problems. The kidneys produce
vitamin D, which helps the body absorb calcium
and keeps bones strong. For patients with kidney
failure, bones may become brittle. In children,
normal growth may be stunted. Joint pain may
also occur as a result of high phosphate levels
in the blood. Retention of uric acid may cause
gout.



edema. Puffiness or swelling in the arms, hands, feet,
and around the eyes.



frequent urination.



foamy or bloody urine. Protein in the urine may
cause it to foam significantly. Blood in the urine
may indicate bleeding from diseased or obstructed
kidneys, bladder, or ureters.



headaches. High blood pressure may trigger
headaches.



hypertension, or high blood pressure. The retention
of fluids and wastes causes blood volume to increase.
This makes blood pressure rise.



increased fatigue. Toxic substances in the blood and
the presence of anemia may cause the patient to feel
exhausted.



itching. Phosphorus, normally eliminated in the
urine, accumulates in the blood of patients with
kidney failure. An increased phosphorus level may
cause the skin to itch.



lower back pain. Patients suffering from certain kidney problems (like kidney stones and other obstructions) may have pain where the kidneys are located,
in the small of the back below the ribs.



nausea. Urea in the gastric juices may cause upset
stomach.

Diagnosis
Kidney failure is diagnosed by a doctor. A
nephrologist, a doctor that specializes in the kidney, may be consulted to confirm the diagnosis and
recommend treatment options. The patient that is
suspected of having acute kidney failure will have
GALE ENCYCLOPEDIA OF MEDICINE

blood and urine tests to determine the level of
kidney function. A blood test will assess the levels
of creatinine, blood urea nitrogen (BUN), uric
acid, phosphate, sodium, and potassium. The kidney regulates these agents in the blood. Urine samples will also be collected, usually over a 24-hour
period, to assess protein loss and/or creatinine
clearance.
Determining the cause of kidney failure is critical
to proper treatment. A full assessment of the kidneys
is necessary to determine if the underlying disease
is treatable and if the kidney failure is chronic or
acute. X rays, magnetic resonance imaging (MRI),
computed tomography scan (CT), ultrasound, renal
biopsy, and/or arteriogram of the kidneys may be
used to determine the cause of kidney failure and
level of remaining kidney function. X rays and ultrasound of the bladder and/or ureters may also be
needed.

Treatment
Treatment for acute kidney failure varies.
Treatment is directed to the underlying, primary medical condition that has triggered kidney failure.
Prerenal conditions may be treated with replacement
fluids given through a vein, diuretics, blood transfusion,
or medications. Postrenal conditions and intrarenal
conditions may require surgery and/or medication.
Frequently, patients in acute kidney failure
require hemodialysis, hemofiltration, or peritoneal
dialysis to filter fluids and wastes from the bloodstream until the primary medical condition can be
controlled.

Hemodialysis
Hemodialysis involves circulating the patient’s
blood outside of the body through an extracorporeal
circuit (ECC), or dialysis circuit. The ECC is made up
of plastic blood tubing, a filter known as a dialyzer (or
artificial kidney), and a dialysis machine that monitors
and maintains blood flow and administers dialysate.
Dialysate is a sterile chemical solution that is used to
draw waste products out of the blood. The patient’s
blood leaves the body through the vein and travels
through the ECC and the dialyzer, where fluid
removal takes place.
During dialysis, waste products in the bloodstream are carried out of the body. At the same time,
electrolytes and other chemicals are added to the
blood. The purified, chemically-balanced blood is
then returned to the body.
47

Acute kidney failure

Common symptoms of acute kidney failure
include:

Acute kidney failure

A dialysis ‘‘run’’ typically lasts three to four hours,
depending on the type of dialyzer used and the physical
condition of the patient. Dialysis is used several times a
week until acute kidney failure is reversed.
Blood pressure changes associated with hemodialysis may pose a risk for patients with heart problems.
Peritoneal dialysis may be the preferred treatment
option in these cases.

Hemofiltration
Hemofiltration, also called continuous renal
replacement therapy (CRRT), is a slow, continuous
blood filtration therapy used to control acute kidney
failure in critically ill patients. These patients are
typically very sick and may have heart problems or
circulatory problems. They cannot handle the rapid
filtration rates of hemodialysis. They also frequently
need antibiotics, nutrition, vasopressors, and other
fluids given through a vein to treat their primary
condition. Because hemofiltration is continuous,
prescription fluids can be given to patients in kidney
failure without the risk of fluid overload.
Like hemodialysis, hemofiltration uses an ECC.
A hollow fiber hemofilter is used instead of a dialyzer
to remove fluids and toxins. Instead of a dialysis
machine, a blood pump makes the blood flow through
the ECC. The volume of blood circulating through
the ECC in hemofiltration is less than that in hemodialysis. Filtration rates are slower and gentler on the
circulatory system. Hemofiltration treatment will
generally be used until kidney failure is reversed.

Peritoneal dialysis
Peritoneal dialysis may be used if an acute kidney
failure patient is stable and not in immediate crisis.
In peritoneal dialysis (PD), the lining of the patient’s
abdomen, the peritoneum, acts as a blood filter.
A flexible tube-like instrument (catheter) is surgically
inserted into the patient’s abdomen. During treatment, the catheter is used to fill the abdominal cavity
with dialysate. Waste products and excess fluids move
from the patient’s bloodstream into the dialysate
solution. After a certain time period, the waste-filled
dialysate is drained from the abdomen, and replaced
with clean dialysate. There are three type of peritoneal
dialysis, which vary according to treatment time and
administration method.
Peritoneal dialysis is often the best treatment
option for infants and children. Their small size can
make vein access difficult to maintain. It is not recommended for patients with abdominal adhesions or
48

other abdominal defects (like a hernia) that might
reduce the efficiency of the treatment. It is also not
recommended for patients who suffer frequent bouts
of an inflammation of the small pouches in the intestinal tract (diverticulitis).

Prognosis
Because many of the illnesses and underlying
conditions that often trigger acute kidney failure
are critical, the prognosis for these patients many
times is not good. Studies have estimated overall
death rates for acute kidney failure at 42-88%.
Many people, however, die because of the primary
disease that has caused the kidney failure. These
figures may also be misleading because patients
who experience kidney failure as a result of less
serious illnesses (like kidney stones or dehydration)
have an excellent chance of complete recovery.
Early recognition and prompt, appropriate treatment are key to patient recovery.
Up to 10% of patients who experience acute
kidney failure will suffer irreversible kidney damage.
They will eventually go on to develop chronic kidney
failure or end-stage renal disease. These patients will
require long-term dialysis or kidney transplantation to
replace their lost renal functioning.

Prevention
Since acute kidney failure can be caused by many
things, prevention is difficult. Medications that may
impair kidney function should be given cautiously.
Patients with pre-existing kidney conditions who are
hospitalized for other illnesses or injuries should be
carefully monitored for kidney failure complications.
Treatments and procedures that may put them at risk
for kidney failure (like diagnostic tests requiring radiocontrast agents or dyes) should be used with extreme
caution.
Resources
PERIODICALS

Stark, June. ‘‘Dialysis Choices: Turning the Tide in Acute
Renal Failure.’’ Nursing 27, no. 2 (February 1997):
41-8.
ORGANIZATIONS

National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.

Paula Anne Ford-Martin

Acute leukemias see Leukemias, acute
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Acute lymphangitis is a bacterial infection in the
lymphatic vessels which is characterized by painful,
red streaks below the skin surface. This is a potentially
serious infection which can rapidly spread to the
bloodstream and be fatal.

Description
Acute lymphangitis affects a critical member of
the immune system–the lymphatic system. Waste
materials from nearly every organ in the body drain
into the lymphatic vessels and are filtered in small
organs called lymph nodes. Foreign bodies, such as
bacteria or viruses, are processed in the lymph nodes
to generate an immune response to fight an infection.
In acute lymphangitis, bacteria enter the body
through a cut, scratch, insect bite, surgical wound, or
other skin injury. Once the bacteria enter the lymphatic system, they multiply rapidly and follow the lymphatic vessel like a highway. The infected lymphatic
vessel becomes inflamed, causing red streaks that are
visible below the skin surface. The growth of the bacteria occurs so rapidly that the immune system does
not respond fast enough to stop the infection.
If left untreated, the bacteria can cause tissue
destruction in the area of the infection. A pus-filled,
painful lump called an abscess may be formed in the
infected area. Cellulitis, a generalized infection of
the lower skin layers, may also occur. In addition,
the bacteria may invade the bloodstream and cause
septicemia. Lay people, for that reason, often call
the red streaks seen in the skin ‘‘blood poisoning.’’
Septicemia is a very serious illness and may be fatal.

Causes and symptoms
Acute lymphangitis is most often caused by the
bacterium Streptococcus pyogenes. This potentially
dangerous bacterium also causes strep throat, infections of the heart, spinal cord, and lungs, and in the
1990s has been called the ‘‘flesh-eating bacterium.’’
Staphylococci bacteria may also cause lymphangitis.
Although anyone can develop lymphangitis, some
people are more at risk. People who have had radical
mastectomy (removal of a breast and nearby lymph
nodes), a leg vein removed for coronary bypass surgery, or recurrent lymphangitis caused by tinea pedis
(a fungal infection on the foot) are at an increased risk
for lymphangitis.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Biopsy—The process which removes a sample of
diseased or infected tissue for microscopic examination to aid in diagnosis.
Lymphatic system—A component of the immune
system consisting of vessels and nodes. Waste
materials from organs drain into the lymphatic vessels and are filtered by the lymph nodes.
Septicemia—Disease caused by the presence and
growth of bacteria in the bloodstream.

The characteristic symptoms of acute lymphangitis are the wide, red streaks which travel from the site
of infection to the armpit or groin. The affected areas
are red, swollen, and painful. Blistering of the affected
skin may occur. The bacterial infection causes a fever
of 100-104 8F (38-40 8C). In addition, a general ill
feeling, muscle aches, headache, chills, and loss of
appetite may be felt.

Diagnosis
If lymphangitis is suspected, the person should
call his or her doctor immediately or go to an emergency room. Acute lymphangitis could be diagnosed
by the family doctor, infectious disease specialist,
or an emergency room doctor. The painful, red
streaks just below the skin surface and the high
fever are diagnostic of acute lymphangitis. A sample
of blood would be taken for culture to determine
whether the bacteria have entered the bloodstream.
A biopsy (removal of a piece of infected tissue)
sample may be taken for culture to identify which
type of bacteria is causing the infection. Diagnosis is
immediate because it is based primarily on the symptoms. Most insurance policies should cover the
expenses for the diagnosis and treatment of acute
lymphangitis.

Treatment
Because of the serious nature of this infection, treatment would begin immediately even before the bacterial
culture results were available. The only treatment for
acute lymphangitis is to give very large doses of an
antibiotic, usually penicillin, through the vein. Growing streptococcal bacteria are usually eliminated rapidly
and easily by penicillin. The antibiotic clindamycin may
be included in the treatment to kill any streptococci
which are not growing and are in a resting state.
49

Acute lymphangitis

I Acute lymphangitis

Acute poststreptococcal glomerulonephritis

Alternatively, a ‘‘broad spectrum’’ antibiotic may be
used which would kill many different kinds of bacteria.

KEY TERMS
Streptococcus—A gram-positive, round or oval
bacteria in the genus Streptococcus. Group A streptococci cause a number of human diseases including strep throat, impetigo, and ASPGN.

Prognosis
Complete recovery is expected if antibiotic treatment is begun at an early stage of the infection.
However, if untreated, acute lymphangitis can be a
very serious and even deadly disease. Acute lymphangitis that goes untreated can spread, causing tissue
damage. Extensive tissue damage would need to be
repaired by plastic surgery. Spread of the infection
into the bloodstream could be fatal.

Prevention
Although acute lymphangitis can occur in anyone, good hygiene and general health may help to
prevent infections.

one to six weeks (average two weeks) after the streptococcal infection.
APSGN is a relatively uncommon disease affecting about one of every 10,000 people, although four or
five times that many may actually be affected by it
but show no symptoms. APSGN is most prevalent
among boys between the ages of 3 and 7, but it can
occur at any age.

Causes and symptoms

Resources
PERIODICALS

Dajer, Tony. ‘‘A Lethal Scratch.’’ Discover (February 1998):
34-7.

Belinda Rowland, PhD

Acute pericarditis see Pericarditis

poststreptococcal
I Acute
glomerulonephritis
Definition
Acute
poststreptococcal
glomerulonephritis
(APSGN) is an inflammation of the kidney tubules
(glomeruli) that filter waste products from the blood,
following a streptococcal infection such as strep
throat. APSGN is also called postinfectious
glomerulonephritis.

Description
APSGN develops after certain streptococcal
bacteria (group A beta-hemolytic streptococci) have
infected the skin or throat. Antigens from the dead
streptococci clump together with the antibodies that
killed them. These clumps are trapped in the kidney
tubules, cause the tubules to become inflamed, and
impair that organs’ ability to filter and eliminate
body wastes. The onset of APSGN usually occurs
50

Frequent sore throats and a history of streptococcal infection increase the risk of acquiring APSGN.
Symptoms of APSGN include:


fluid accumulation and tissue swelling (edema)
initially in the face and around the eyes, later in
the legs



low urine output (oliguria)



blood in the urine (hematuria)



protein in the urine (proteinuria)



high blood pressure



joint pain or stiffness

Diagnosis
Diagnosis of APSGN is made by taking the
patient’s history, assessing his/her symptoms, and
performing certain laboratory tests. Urinalysis
usually shows blood and protein in the urine.
Concentrations of urea and creatinine (two waste
products normally filtered out of the blood by the
kidneys) in the blood are often high, indicating
impaired kidney function. A reliable, inexpensive
blood test called the anti-streptolysin-O test can
confirm that a patient has or has had a streptococcal infection. A throat culture may also show the
presence of group A beta-hemolytic streptococci.

Treatment
Treatment of ASPGN is designed to relieve the
symptoms and prevent complications. Some patients
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Depersonalization—A dissociative symptom in
which the patient feels that his or her body is
unreal, is changing, or is dissolving.
Derealization—A dissociative symptom in which
the external environment is perceived as unreal.

Prognosis

Dissociation—A reaction to trauma in which the
mind splits off certain aspects of the trauma from conscious awareness. Dissociation can affect the patient’s memory, sense of reality, and sense of identity.

Most children (up to 95%) fully recover from
APSGN in a matter of weeks or months. Most adults
(up to 70%) also recover fully. In those who do
not recover fully, chronic or progressive problems of
kidney function may occur. Kidney failure may result
in some patients.

Trauma—In the context of ASD, a disastrous or
life-threatening event.

Description

Prevention
Receiving prompt treatment for streptococcal
infections may prevent APSGN.
Resources

Acute stress disorder is a new diagnostic category
that was introduced in 1994 to differentiate time-limited reactions to trauma from post-traumatic stress
disorder (PTSD).

BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.
ORGANIZATIONS

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New
York, NY 10016. (800) 622-9010.<http://
www.kidney.org>.

Maureen Haggerty

Acute respiratory distress syndrome see
Adult respiratory distress syndrome

I Acute stress disorder
Definition
Acute stress disorder (ASD) is an anxiety disorder
characterized by a cluster of dissociative and anxiety
symptoms occurring within one month of a traumatic
event. (Dissociation is a psychological reaction to
trauma in which the mind tries to cope by ‘‘sealing
off ’’ some features of the trauma from conscious
awareness).
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Acute stress disorder is caused by exposure to
trauma, which is defined as a stressor that causes
intense fear and, usually, involves threats to life or
serious injury to oneself or others. Examples are
rape, mugging, combat, natural disasters, etc.
The symptoms of stress disorder include a combining of one or more dissociative and anxiety symptoms with the avoidance of reminders of the traumatic
event. Dissociative symptoms include emotional
detachment, temporary loss of memory, depersonalization, and derealization.
Anxiety symptoms connected with acute stress
disorder include irritability, physical restlessness,
sleep problems, inability to concentrate, and being
easily startled.

Diagnosis
Diagnosis of acute stress disorder is based on a
combination of the patient’s history and a physical
examination to rule out diseases that can cause
anxiety. The essential feature is a traumatic event
within one month of the onset of symptoms. Other
diagnostic criteria include:


The symptoms significantly interfere with normal
social or vocational functioning



The symptoms last between two days and four weeks.
51

Acute stress disorder

are advised to stay in bed until they feel better and
to restrict fluid and salt intake. Antibiotics may be
prescribed to kill any lingering streptococcal bacteria,
if their presence is confirmed. Antihypertensives may
be given to help control high blood pressure and
diuretics may be used to reduce fluid retention and
swelling. Kidney dialysis is rarely needed.

Addiction

Treatment
Treatment for acute stress disorder usually
includes a combination of antidepressant medications
and short-term psychotherapy.

Prognosis
The prognosis for recovery is influenced by the
severity and duration of the trauma, the patient’s
closeness to it, and the patient’s previous level of functioning. Favorable signs include a short time period
between the trauma and onset of symptoms, immediate
treatment, and appropriate social support. If the
patient’s symptoms are severe enough to interfere
with normal life and have lasted longer than one
month, the diagnosis may be changed to PTSD. If the
symptoms have lasted longer than one month but are
not severe enough to meet the definition of PTSD, the
diagnosis may be changed to adjustment disorder.
Patients who do not receive treatment for acute
stress disorder are at increased risk for substance abuse
or major depressive disorders.

Prevention
Traumatic events cannot usually be foreseen and,
thus, cannot be prevented. However, in theory, professional intervention soon after a major trauma might
reduce the likelihood or severity of ASD. In addition,
some symptoms of acute stress disorder result from
biochemical changes in the central nervous system,
muscles, and digestive tract that are not subject to
conscious control.
Resources
BOOKS

Corbman, Gene R. ‘‘Anxiety Disorders.’’ In Current
Diagnosis, edited by Rex B. Conn, et al. Vol. 9.
Philadelphia: W. B. Saunders Co., 1997.
Eisendrath, Stuart J. ‘‘Psychiatric Disorders.’’ In Current
Medical Diagnosis and Treatment, 1998, edited by
Stephen McPhee, et al., 37th ed. Stamford: Appleton &
Lange, 1997.

Rebecca J. Frey, PhD

Acute stress gastritis see Gastritis
Acute transverse myelitis see Transverse
myelitis
Acyclovir see Antiviral drugs
52

I Addiction
Definition
Addiction is a persistent, compulsive dependence
on a behavior or substance. The term has been partially replaced by the word dependence for substance
abuse. Addiction has been extended, however, to
include mood-altering behaviors or activities. Some
researchers speak of two types of addictions: substance addictions (for example, alcoholism, drug
abuse, and smoking); and process addictions (for
example, gambling, spending, shopping, eating, and
sexual activity). There is a growing recognition that
many addicts, such as polydrug abusers, are addicted
to more than one substance or process.

Description
Addiction is one of the most costly public
health problems in the United States. It is a progressive syndrome, which means that it increases in
severity over time unless it is treated. Substance
abuse is characterized by frequent relapse, or return
to the abused substance. Substance abusers often
make repeated attempts to quit before they are
successful.
The economic cost of substance abuse in the
United States exceeds $414 billion, with health care
costs attributed to substance abuse estimated at more
than $114 billion.
By eighth grade, 52% of adolescents have consumed alcohol, 41% have smoked tobacco, and 20%
have smoked marijuana. Compared to females, males
are almost four times as likely to be heavy drinkers,
nearly one and a half more likely to smoke a pack or
more of cigarettes daily, and twice as likely to smoke
marijuana weekly. However, among adolescents
these gender differences are not as pronounced and
girls are almost as likely to abuse substances such
as alcohol and cigarettes. Although frequent use
of tobacco, cocaine and heavy drinking appears
to remain stable in the 1990s, marijuana use has
increased.
An estimated four million Americans over the age
of 12 used prescription pain relievers, sedatives, and
stimulants for ‘‘nonmedical’’ reasons during one
month.
In the United States, 25% of the population regularly uses tobacco. Tobacco use reportedly kills 2.5
times as many people each year as alcohol and drug
abuse combined. According to data from the World
GALE ENCYCLOPEDIA OF MEDICINE

Addictive personality—A concept that was formerly used to explain addiction as the result of
pre-existing character defects in individuals.
Process addiction—Addiction to certain moodaltering behaviors, such as eating disorders, gambling, sexual activity, overwork, and shopping.
Tolerance—A condition in which an addict needs
higher doses of a substance to achieve the same
effect previously achieved with a lower dose.
Withdrawal—The unpleasant, sometimes lifethreatening physiological changes that occur, due
to the discontinuation of use of some drugs after
prolonged, regular use.

Causes and symptoms
Addiction to substances results from the interaction of several factors:
Drug chemistry
Some substances are more addictive than others,
either because they produce a rapid and intense
change in mood; or because they produce painful
withdrawal symptoms when stopped suddenly.
Crack users. Crack, a form of cocaine, is one of the most
addictive drugs. (Photograph by Roy Marsch, The Stock
Market. Reproduced by permission.)

Health Organization, there were 1.1 billion smokers
worldwide and 10,000 tobacco-related deaths per
day. Furthermore, in the United States, 43% of children aged 2-11 years are exposed to environmental
tobacco smoke, which has been implicated in sudden
infant death syndrome, low birth weight, asthma, middle ear disease, pneumonia, cough, and upper respiratory infection.
Eating disorders, such as anorexia nervosa,
bulimia nervosa, and binge eating, affect more than
five million American women and men. Fifteen percent of young women have substantially disordered
attitudes toward eating and eating behaviors. More
than 1,000 women die each year from anorexia
nervosa.
A Harvard study found that an estimated 15.4
million Americans suffered from a gambling addiction.
More than one-half (7.9 million) were adolescents.
GALE ENCYCLOPEDIA OF MEDICINE

Genetic factor
Some people appear to be more vulnerable to
addiction because their body chemistry increases
their sensitivity to drugs. Some forms of substance
abuse and dependence seem to run in families; and
this may be the result of a genetic predisposition,
environmental influences, or a combination of both.
Brain structure and function
Using drugs repeatedly over time changes brain
structure and function in fundamental and long-lasting ways. Addiction comes about through an array of
changes in the brain and the strengthening of new
memory connections. Evidence suggests that those
long-lasting brain changes are responsible for the distortions of cognitive and emotional functioning that
characterize addicts, particularly the compulsion to
use drugs. Although the causes of addiction remain
the subject of ongoing debate and research, many
experts now consider addiction to be a brain disease:
a condition caused by persistent changes in brain
structure and function. However, having this brain
53

Addiction

KEY TERMS

Addiction

disease does not absolve the addict of responsibility
for his or her behavior, but it does explain why many
addicts cannot stop using drugs by sheer force of will
alone.
Scientists may have come closer to solving the
brain’s specific involvement in addiction in 2004.
Psychiatrists say they have found the craving center
of the brain that triggers relapse in addicts. The anterior cingulated cortex in the frontal lobe of the brain is
the area responsible for long-term craving in addicts.
Knowing the area of the brain from which long-term
cravings come may help scientists pinpoint therapies.
Social learning
Social learning is considered the most important
single factor in addiction. It includes patterns of use in
the addict’s family or subculture, peer pressure, and
advertising or media influence.
Availability
Inexpensive or readily available tobacco, alcohol,
or drugs produce marked increases in rates of
addiction.
Individual development
Before the 1980s, the so-called addictive personality was used to explain the development of addiction. The addictive personality was described as
escapist, impulsive, dependent, devious, manipulative,
and self-centered. Many doctors now believe that
these character traits develop in addicts as a result of
the addiction, rather than the traits being a cause of
the addiction.

Diagnosis
In addition to a preoccupation with using and
acquiring the abused substance, the diagnosis of
addiction is based on five criteria:


loss of willpower



harmful consequences



unmanageable lifestyle



tolerance or escalation of use



withdrawal symptoms upon quitting

group psychotherapy is often helpful, but only after
substance use has stopped. Anti-addiction medications,
such as methadone and naltrexone, are also commonly
used. A new treatment option has been developed that
allows family physicians to treat heroine addiction
from their offices rather than sending patients to
methadone clinics. The drug is called buprenorphine
(Suboxone).
Researchers continue to work to identify workable pharmacological treatments for various addictions. In 2004, clinical trials were testing a number of
drugs currently in use for other diseases and conditions to see if they could be used to treat addiction.
This would speed up their approval by the U.S. Food
and Drug Administration (FDA). For example,
cocaine withdrawal is eased by boosting dopamine
levels in the brain, so scientists are studying drugs
that boost dopamine, such as Ritalin, which is used
to treat attention-deficit hyperactivity disorder, and
amantadine, a drug used for flu and Parkinson’s
diease.
The most frequently recommended social form of
outpatient treatment is the twelve-step program. Such
programs are also frequently combined with psychotherapy. According to a recent study reported
by the American Psychological Association (APA),
anyone, regardless of his or her religious beliefs or
lack of religious beliefs, can benefit from participation
in 12-step programs such as Alcoholics Anonymous
(AA) or Narcotics Anonymous (NA). The number of
visits to 12-step self-help groups exceeds the number of
visits to all mental health professionals combined.
There are twelve-step groups for all major substance
and process addictions.
The Twelve Steps are:


Admit powerlessness over the addiction.



Believe that a Power greater than oneself could
restore sanity.



Make a decision to turn your will and your life over
to the care of God, as you understand him.



Make a searching and fearless moral inventory of
self.



Admit to God, yourself, and another human being
the exact nature of your wrongs.



Become willing to have God remove all these defects
from your character.



Humbly ask God to remove shortcomings.



Make a list of all persons harmed by your wrongs
and become willing to make amends to them all.

Treatment
Treatment requires both medical and social
approaches. Substance addicts may need hospital treatment to manage withdrawal symptoms. Individual or
54

GALE ENCYCLOPEDIA OF MEDICINE

Make direct amends to such people, whenever possible except when to do so would injure them or others.



Continue to take personal inventory and promptly
admit any future wrongdoings.



Seek to improve contact with a God of the individual’s understanding through meditation and prayer.



Carry the message of spiritual awakening to others
and practice these principles in all your affairs.

Prognosis
The prognosis for recovery from any addiction
depends on the substance or process, the individual’s
circumstances, and underlying personality structure.
Polydrug users have the worst prognosis for recovery.

American Psychiatric Association.
<http://www.pscyh.org>.
Center for On-Line Addiction.
<http://www.netaddiction.com>.
eGambling: Electronic Joural of Gambling Issues.
<http://www.camh.net/egambling/main.html>.
National Alliance on Alcoholism and Drug Dependence,
Inc. 12 West 21st St., New York, NY 10010. (212)
206-6770.
National Center on Addiction and Substance Abuse at
Columbia University.
<http://www.casacolumbia.org>.
National Clearinghouse for Alcohol and Drug Information.
<http://www.health.org>.
National Institute on Alcohol Abuse and Alcoholism
(NIAAA). 6000 Executive Boulevard, Bethesda,
Maryland 20892-7003. <http://www.niaaa.nih.gov>.

Bill Asenjo, MS, CRC
Teresa G. Odle

Prevention
The most effective form of prevention appears to
be a stable family that models responsible attitudes
toward mood-altering substances and behaviors.
Prevention education programs are also widely used
to inform the public of the harmfulness of substance
abuse.

I Addison’s disease
Definition

Resources
BOOKS

Robert Wood Johnson Foundation. Substance Abuse: The
Nation’s #1 Problem. Princeton, N.J., 2001.
PERIODICALS

Kalivas, Peter. ‘‘Drug Addiction: To the Cortex . . . and
Beyond.’’ The American Journal of Psychiatry 158, no. 3
(March 2001).
Kelly, Timothy. ‘‘Addiction: A Booming $800 Billion
Industry.’’ The World and I (July 1, 2000).
Leshner, Alan. ‘‘Addiction is a Brain Disease.’’ Issues in
Science and Technology 17, no. 3 (April 1, 2001).
‘‘A New Office-based Treatment for Prescription Drug and
Heroin Addiction.’’ Biotech Week (August 4, 2004):
219.
‘‘Research Brief: Source of Addiction Identified.’’ GP (July
19, 2004): 4.
‘‘Scientists May Use Existing Drugs to Stop Addiction.’’
Life Science Weekly (Sepember 21, 2004): 1184.
ORGANIZATIONS

Al-Anon Family Groups. Box 182, Madison Square Station,
New York, NY 10159. <http://www.Al-Anon
Alateen.org>.
Alcoholics Anonymous World Services, Inc. Box 459,
Grand Central Station, New York, NY 10163. <http://
www.alcoholics-anonymous.org>.
American Anorexia Bulimina Association.
<http://www.aabainc.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Addison’s disease is a disorder involving disrupted functioning of the part of the adrenal gland
called the cortex. This results in decreased production
of two important chemicals (hormones) normally
released by the adrenal cortex: cortisol and
aldosterone.

Description
The adrenals are two glands, each perched on the
upper part of the two kidneys. The outer part of the
gland is known as the cortex; the inner part is known
as the medulla. Each of these parts of the adrenal
gland is responsible for producing different types of
hormones.
Cortisol is a very potent hormone produced by the
adrenal cortex. It is involved in regulating the functioning of nearly every type of organ and tissue
throughout the body, and is considered to be one of
the few hormones absolutely necessary for life.
Cortisol is involved in:


the very complex processing and utilization of many
nutrients, including sugars (carbohydrates), fats, and
proteins



the normal functioning of the circulatory system and
the heart
55

Addison’s disease



Addison’s disease



the functioning of muscles



normal kidney function



production of blood cells



the normal processes involved in maintaining the
skeletal system



proper functioning of the brain and nerves



the normal responses of the immune system

Aldosterone, also produced by the adrenal cortex,
plays a central role in maintaining the appropriate
proportions of water and salts in the body. When
this balance is upset, the volume of blood circulating
throughout the body will fall dangerously low, accompanied by a drop in blood pressure.
Addison’s disease is also called primary adrenocortical insufficiency. In other words, some process
interferes directly with the ability of the adrenal cortex
to produce its hormones. Levels of both cortisol and
aldosterone drop, and numerous functions throughout the body are disrupted.
Addison’s disease occurs in about four in every
100,000 people. It strikes both men and women of all
ages.

Causes and symptoms
The most common cause of Addison’s disease is
the destruction and/or shrinking (atrophy) of the adrenal cortex. In about 70% of all cases, this atrophy is
believed to occur due to an autoimmune disorder. In an
autoimmune disorder, the immune system of the body,
responsible for identifying foreign invaders such as
viruses or bacteria and killing them, accidentally begins
to identify the cells of the adrenal cortex as foreign,
and destroy them. In about 20% of all cases, destruction of the adrenal cortex is caused by tuberculosis. The
remaining cases of Addison’s disease may be caused
by fungal infections, such as histoplasmosis, coccidiomycosis, and cryptococcosis, which affect the adrenal
gland by producing destructive, tumor-like masses
called granulomas; a disease called amyloidosis, in
which a starchy substance called amyloid is deposited
in abnormal places throughout the body, interfering
with the function of whatever structure it is present
within; or invasion of the adrenal glands by cancer.
In about 75% of all patients, Addison’s disease
tends to be a very gradual, slowly developing disease.
Significant symptoms are not noted until about
90% of the adrenal cortex has been destroyed. The
most common symptoms include fatigue and loss
of energy, decreased appetite, nausea, vomiting, diarrhea, abdominal pain, weight loss, muscle weakness,
56

KEY TERMS
Gland—A collection of cells whose function is to
release certain chemicals, or hormones, which are
important to the functioning of other, sometimes
distantly located, organs or body systems.
Hormone—A chemical produced in one part of the
body, which travels to another part of the body in
order to exert its effect.

dizziness when standing, dehydration, unusual areas of
darkened (pigmented) skin, and dark freckling. As the
disease progresses, the patient may appear to have
very tanned, or bronzed skin, with darkening of the
lining of the mouth, vagina, and rectum, and dark
pigmentation of the area around the nipples (aereola). As dehydration becomes more severe, the
blood pressure will continue to drop and the patient
will feel increasingly weak and light-headed. Some
patients have psychiatric symptoms, including
depression and irritability. Women lose pubic and
underarm hair, and stop having normal menstrual
periods.
When a patient becomes ill with an infection,
or stressed by an injury, the disease may suddenly and
rapidly progress, becoming life-threatening. Symptoms
of this ‘‘Addisonian crisis’’ include abnormal heart
rhythms, severe pain in the back and abdomen,
uncontrollable nausea and vomiting, a drastic drop in
blood pressure, kidney failure, and unconsciousness.
About 25% of all Addison’s disease patients are
identified due to the development of Addisonian crisis.

Diagnosis
Many patients do not recognize the slow progression of symptoms and the disease is ultimately identified when a physician notices the areas of increased
pigmentation of the skin. Once suspected, a number
of blood tests can lead to the diagnosis of Addison’s
disease. It is not sufficient to demonstrate low blood
cortisol levels, as normal levels of cortisol vary quite
widely. Instead, patients are given a testing dose of
another hormone called corticotropin (ACTH).
ACTH is produced in the body by the pituitary
gland, and normally acts by promoting growth
within the adrenal cortex and stimulating the production and release of cortisol. In Addison’s disease,
even a dose of synthetic ACTH does not increase
cortisol levels.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Treatment of Addison’s disease involves replacing the missing or low levels of cortisol. In the case
of Addisonian crisis, this will be achieved by injecting
a potent form of steroid preparation through a needle
placed in a vein (intravenous or IV). Dehydration
and salt loss will also be treated by administering
carefully balanced solutions through the IV.
Dangerously low blood pressure may require special
medications to safely elevate it until the steroids take
effect.
Patients with Addison’s disease will need to take a
steroid preparation (hydrocortisone) and a replacement for aldosterone (fludrocortisone) by mouth for
the rest of their lives. When a patient has an illness
which causes nausea and vomiting (such that they
cannot hold down their medications), he or she will
need to enter a medical facility where IV medications
can be administered. When a patient has any kind of
infection or injury, the normal dose of hydrocortisone
will need to be doubled.

I Adenoid hyperplasia
Definition
Adenoid hyperplasia is the overenlargement of
the lymph glands located above the back of the mouth.

Description
Located at the back of the mouth above and
below the soft palate are two pairs of lymph glands.
The tonsils below are clearly visible behind the back
teeth; the adenoids lie just above them and are hidden
from view by the palate. Together these four arsenals
of immune defense guard the major entrance to the
body from foreign invaders–the germs we breathe and
eat. In contrast to the rest of the body’s tissues, lymphoid tissue reaches its greatest size in mid-childhood
and recedes thereafter. In this way children are best
able to develop the immunities they need to survive in
a world full of infectious diseases.
Beyond its normal growth pattern, lymphoid tissue grows excessively (hypertrophies) during an acute
infection, as it suddenly increases its immune activity
to fight off the invaders. Often it does not completely
return to its former size. Each subsequent infection
leaves behind a larger set of tonsils and adenoids. To
make matters worse, the sponge-like structure of these
hypertrophied glands can produce safe havens for
germs where the body cannot reach and eliminate
them. Before antibiotics and the reduction in infectious
childhood diseases over the past few generations, tonsils and adenoids caused greater health problems.

Prognosis
Prognosis for patients appropriately treated with
hydrocortisone and aldosterone is excellent. These
patients can expect to enjoy a normal lifespan. Without
treatment, or with substandard treatment, patients
are always at risk of developing Addisonian crisis.
Resources
BOOKS

Williams, Gordon H., and Robert G. Dluhy.
‘‘Hypofunction of the Adrenal Cortex.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony
S.Fauci, et al. New York: McGraw-Hill, 1997.
ORGANIZATIONS

National Adrenal Disease Foundation. 505 Northern
Boulevard, Suite 200, Great Neck, NY 11021. (516)
487-4992.

Rosalyn Carson-DeWitt, MD
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Most tonsil and adenoid hypertrophy is simply
caused by the normal growth pattern for that type of
tissue. Less often, the hypertrophy is due to repeated
throat infections by cold viruses, strep throat, mononucleosis, and in times gone by, diphtheria. The acute
infections are usually referred to as tonsillitis, the adenoids getting little recognition because they cannot be
seen without special instruments. Symptoms include
painful, bright red, often ulcerated tonsils, enlargement of lymph nodes (glands) beneath the jaw, fever,
and general discomfort.
After the acute infection subsides, symptoms are
generated simply by the size of the glands. Extremely
large tonsils can impair breathing and swallowing,
although that is quite rare. Large adenoids can impair
nose breathing and require a child to breathe through
the mouth. Because they encircle the only connection
57

Adenoid hyperplasia

To distinguish between primary adrenocortical
insufficiency (Addison’s disease) and secondary adrenocortical insufficiency (caused by failure of the pituitary to produce enough ACTH), levels of ACTH in
the blood are examined. Normal or high levels of
ACTH indicate that the pituitary is working properly,
but the adrenal cortex is not responding normally
to the presence of ACTH. This confirms the diagnosis
of Addison’s disease.

Adenovirus infections

KEY TERMS
Eustacian tube—A tube connecting the middle ear
with the back of the nose, allowing air pressure to
equalize within the ear whenever it opens, such as
with yawning.
Hyperplastic—Overgrown.
Hypertrophy—Overgrowth.
Strep throat—An infection of the throat caused by
bacteria of the Streptococcus family, which causes
tonsillitis.
Ulcerated—Damaged so that the surface tissue is
lost and/or necrotic (dead).

contribution to optimal function in the tonsils and
adenoids. Food allergies are often the culprits for
recurring ear infections, as well as tonsilitis and adenoiditis. Identification and removal of the allergic
food(s) can greatly assist in alleviating the cause of
the problem. Acute tonsillitis also benefits from
warm saline gargles.

Prognosis
Hypertrophied adenoids are a normal part of
growing up and should be respected for their important role in the development of immunity. Only when
their size causes problems by obstructing breathing or
middle ear drainage do they demand intervention.

Prevention
between the middle ear and the eustachian tube,
hypertrophied adenoids can also obstruct it and
cause middle ear infections.

Diagnosis
A simple tongue blade depressing the tongue
allows an adequate view of the tonsils. Enlarged tonsils may have deep pockets (crypts) containing dead
tissue (necrotic debris). Viewing adenoids requires a
small mirror or fiberoptic scope. A child with recurring
middle ear infections may well have large adenoids. A
throat culture or mononucleosis test will usually reveal
the identity of the germ.

Treatment
It used to be standard practice to remove tonsils
and/or adenoids after a few episodes of acute throat or
ear infection. The surgery is called tonsillectomy and
adenoidectomy (T and A). Opinion changed as it was
realized that this tissue is beneficial to the development
of immunity. For instance, children without tonsils
and adenoids produce only half the immunity to oral
polio vaccine. In addition, treatment of ear and throat
infections with antibiotics and of recurring ear infections with surgical drainage through the ear drum
(tympanostomy) has greatly reduced the incidence of
surgical removal of these lymph glands.

Alternative treatment
There are many botanical/herbal remedies that
can be used alone or in formulas to locally assist the
tonsils and adenoids in their immune function at the
opening of the oral cavity and to tone these glands.
Keeping the Eustachian tubes open is an important
58

Prevention can be directed toward prompt evaluation and appropriate treatment of sore throats to prevent overgrowth of adenoid tissue. Avoiding other
children with acute respiratory illness will also reduce
the spread of these common illnesses.
Resources
BOOKS

Behman, Richard E., editor. ‘‘Tonsils and Adenoids.’’ In
Nelson Textbook of Pediatrics. Philadelphia: W. B.
Saunders Co., 1996.

J. Ricker Polsdorfer, MD

Adenoid hypertrophy see Adenoid
hyperplasia
Adenoid removal see Tonsillectomy
and adenoidectomy
Adenoidectomy see Tonsillectomy
and adenoidectomy

I Adenovirus infections
Definition
Adenoviruses are DNA viruses (small infectious
agents) that cause upper respiratory tract infections,
conjunctivitis, and other infections in humans.

Description
Adenoviruses were discovered in 1953. About 47
different types have been identified since then, and
GALE ENCYCLOPEDIA OF MEDICINE

Conjunctivitis—Inflammation of the conjunctiva,
the mucous membrane lining the inner surfaces of
the eyelid and the front of the eyeball.
Virus—A small infectious agent consisting of a core
of genetic material (DNA or RNA) surrounded by a
shell of protein.

about half of them are believed to cause human diseases. Infants and children are most commonly
affected by adenoviruses. Adenovirus infections can
occur throughout the year, but seem to be most common from fall to spring.
Adenoviruses are responsible for 3-5% of acute
respiratory infections in children and 2% of respiratory illnesses in civilian adults. They are more apt to
cause infection among military recruits and other
young people who live in institutional environments.
Outbreaks among children are frequently reported at
boarding schools and summer camps. Another example includes an increased outbreak of gastroenteritis
among cruise passengers in 2002.

by types 3 and 7. Symptoms, which appear suddenly
and usually disappear in less than a week, include:


inflammation of the lining of the eyelid (conjunctivitis)



fever



sore throat (pharyngitis)



runny nose



inflammation of lymph glands in the neck (cervical
adenitis)

Adenoviruses also cause acute diarrhea in young
children, characterized by fever and watery stools.
This condition is caused by adenovirus types 40 and
41 and can last as long as two weeks.
As much as 51% of all hemorrhagic cystitis
(inflammation of the bladder and of the tubes that
carry urine to the bladder from the kidneys) in
American and Japanese children can be attributed to
adenovirus infection. A child who has hemorrhagic
cystitis has bloody urine for about three days, and
invisible traces of blood can be found in the urine a
few days longer. The child will feel the urge to urinate
frequently–but find it difficult to do so–for about the
same length of time.
Adult infections

Acquired immunity
Most children have been infected by at least one
adenovirus by the time they reach school age. Most
adults have acquired immunity to multiple adenovirus
types due to infections they had as children.
In one mode of adenovirus infection (called lytic
infection because it destroys large numbers of cells),
adenoviruses kill healthy cells and replicate up to
one million new viruses per cell killed (of which 1-5%
are infectious). People with this kind of infection feel
sick. In chronic or latent infection, a much smaller number of viruses are released and healthy cells can multiply
more rapidly than they are destroyed. People who have
this kind of infection don’t seem to be sick. This is
probably why many adults have immunity to adenoviruses without realizing they have been infected.
Childhood infections
In children, adenoviruses most often cause acute
upper respiratory infections with fever and runny nose.
Adenovirus types 1, 2, 3, 5, and 6 are responsible for most
of these infections. Occasionally more serious lower
respiratory diseases, such as pneumonia, may occur.
Adenoviruses also cause acute pharyngoconjunctival fever in children. This disease is most often caused
GALE ENCYCLOPEDIA OF MEDICINE

In adults, the most frequently reported adenovirus infection is acute respiratory disease (ARD,
caused by types 4 and 7) in military recruits.
Influenza-like symptoms including fever, sore throat,
runny nose, and cough are almost always present;
weakness, chills, headache, and swollen lymph glands
in the neck also may occur. The symptoms typically
last three to five days.
Epidemic keratoconjunctivitis (EKC, caused by
adenovirus types 8, 19, and 37) was first seen in shipyard workers whose eyes had been slightly injured by
chips of rust or paint. This inflammation of tissues
lining the eyelid and covering the front of the eyeball
also can be caused by using contaminated contact lens
solutions or by drying the hands or face with a towel
used by someone who has this infection.
The inflamed, sticky eyelids characteristic of
conjunctivitis develop 4-24 days after exposure and
last between one and four weeks. Only 5-8% of
patients with epidemic keratoconjunctivitis experience
respiratory symptoms. One or both eyes may be
affected. As symptoms of conjunctivitis subside, eye
pain and watering and blurred vision develop. These
symptoms of keratitis may last for several months, and
about 10% of these infections spread to at least one
other member of the patient’s household.
59

Adenovirus infections

KEY TERMS

Adenovirus infections

Other illnesses associated with adenovirus include:


encephalitis (inflammation of the brain) and other
infections of the central nervous system (CNS)



gastroenteritis (inflammation of the stomach and
intestines)



acute mesenteric lymphadenitis (inflammation of
lymph glands in the abdomen)



chronic interstitial fibrosis (abnormal growth of
connective tissue between cells)



intussusception (a type of intestinal obstruction)



pneumonia that doesn’t respond to antibiotic therapy



whooping cough syndrome when Bordetella pertussis
(the bacterium that causes classic whooping cough) is
not found

Causes and symptoms
Specific adenovirus infections can be traced to
particular sources and produce distinctive symptoms.
In general, however, adenovirus infection is caused by:


inhaling airborne viruses



getting the virus in the eyes by swimming in contaminated water, using contaminated eye solutions or
instruments, wiping the eyes with contaminated
towels, or rubbing the eyes with contaminated fingers.



not washing the hands after using the bathroom, and
then touching the mouth or eyes

Symptoms common to most types of adenovirus
infections include:


cough



fever



runny nose



sore throat



watery eyes

Treatment
Treatment of adenovirus infections is usually
supportive and aimed at relieving symptoms of the
illness. Bed rest may be recommended along with
medications to reduce fever and/or pain. (Aspirin
should not be given to children because of concerns
about Reye’s syndrome.) Eye infections may benefit
from topical corticosteroids to relieve symptoms and
shorten the course of the disease. Hospitalization is
usually required for severe pneumonia in infants and
for EKC (to prevent blindness). No effective antiviral
drugs have been developed.

Prognosis
Adenovirus infections are rarely fatal. Most
patients recover fully.

Prevention
Practicing good personal hygiene and avoiding
people with infectious illnesses can reduce the
risk of developing adenovirus infection. Proper handwashing can prevent the spread of the virus by oralfecal transmission. Sterilization of instruments and
solutions used in the eye can prevent the spread of
EKC, as can adequate chlorination of swimming
pools.
A vaccine for pertussis has been developed
and is in use in combination with diphtheria and tetanus vaccines for infants. It is shown to have nearly
90% efficacy. A vaccine containing live adenovirus
types 4 and 7 is used to control disease in military
recruits, but it is not recommended or available for
civilian use. A recent resurgence of the adenovirus
was found in a military population as soon as the
vaccination program was halted. Vaccines prepared
from purified subunits of adenovirus are under
investigation.
Resources

Diagnosis
Although symptoms may suggest the presence of
adenovirus, distinguishing these infections from other
viruses can be difficult. A definitive diagnosis is based
on culture or detection of the virus in eye secretions,
sputum, urine, or stool.
The extent of infection can be estimated from the
results of blood tests that measure increases in the
quantity of antibodies the immune system produces to
fight it. Antibody levels begin to rise about a week after
infection occurs and remain elevated for about a year.
60

PERIODICALS

Evans, Jeff. ‘‘Viral Gastroenteritis On Board.’’ Internal
Medicine News (January 15, 2003): 44.
‘‘Guard Against Pertussis.’’ Contemporary Pediatrics
(February 2003): 87.
Kolavic-Gray, Shellie A., et al. ‘‘Large Epidemic of
Adenovirus Type 4 Infection Among Military Trainees:
Epidemiological, Clinical, and Laboratory Studies.’’
Clinical Infectious Diseases (October 1, 2002): 808–811.

Maureen Haggerty
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Adhesions are fibrous bands of scar tissue that
form between internal organs and tissues, joining
them together abnormally.

Description
Adhesions are made up of blood vessels and fibroblasts—connective tissue cells. They form as a normal
part of the body’s healing process and help to limit
the spread of infection. However when adhesions
cause the wrong tissues to grow into each other,
many different complex inflammatory disorders can
arise. Worldwide millions of people suffer pain and
dysfunction due to adhesion disease.
Depending on their location, the most common
types of adhesions may called:


abdominal adhesions



intestinal adhesions



intraperitoneal adhesions



pelvic adhesions



intrauterine adhesions or Asherman’s syndrome.

Adhesions can form between various tissues in the
body including:


loops of the intestines



the intestines and other abdominal organs or the
abdominal wall



abdominal organs such as the liver or bladder and
the abdominal wall



tissues of the uterus.

Although adhesions can be congenital (present at
birth) or result from inflammation, injury, or infection, the vast majority of adhesions form following
surgery. Adhesions are a major complication of
many common surgical procedures and may occur in
55% to more than 90% of patients, depending on the
type of surgery.
All abdominal surgeries carry the risk of adhesion
formation. Abdominal adhesions are rare in people
who have not had abdominal surgery and very common in people who have had multiple abdominal surgeries. Adhesions are more common following
procedures involving the intestines, colon, appendix,
or uterus. They are less common following surgeries
involving the stomach, gall bladder, or pancreas.

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Asherman’s syndrome—The cessation of menstruation and/or infertility caused by intrauterine
adhesions.
Computed axial tomography; CT or CAT scan—A
computer reconstruction of scanned x rays used to
diagnose intestinal obstructions.
Endometriosis—A condition in which the endometrial tissue that lines the uterus begins to invade
other parts of the body.
Endoscope—A device with a light that is used to
look into a body cavity or organ.
Fibroblast—A connective-tissue cell.
Glaucoma—A group of eye diseases characterized
by increased pressure within the eye that can
damage the optic nerve and cause gradual loss of
vision.
Hysteroscopy—A procedure in which an endoscope is inserted through the cervix to view the
cervix and uterus.
Hysterosalpingography; HSG—X raying of the
uterus and fallopian tubes following the injection
of a contrast dye.
Irido corneal endothelial syndrome; ICE—A type
of glaucoma in which cells from the back of the
cornea spread over the surface of the iris and tissue
that drains the eye, forming adhesions that bind the
iris to the cornea.
Laparoscopic surgery; keyhole surgery—Surgery
that utilizes a laparoscope with a video camera and
surgical instruments inserted through small incisions.
Laparoscopy—A procedure that utilizes an endoscope to view contents of the abdominal cavity.
Pelvic inflammatory disease; PID—Inflammation
of the female reproductive organs and associated
structures.
Peritoneum—The membrane lining the walls of the
abdominal and pelvic cavities and enclosing their
organs.
Small bowel obstruction; SBO—An obstruction of
the small intestine that prevents the free passage of
material; sometimes caused by postoperative
adhesions.

Although most abdominal adhesions do not cause
problems, they can be painful when stretched or pulled
because the scar tissue is not elastic.

61

Adhesions

I Adhesions

Adhesions

Postoperative intestinal adhesions are a major
cause of intestinal or small bowel obstruction (SBO).
In a small number of people the scar tissue pulls sections of the small or large intestines out of place and
partially or completely blocks the passage of food and
fluids. Thus SBOs can result from abdominal surgery
and also are one of the most common reasons for
abdominal surgery. Although intestinal obstruction
is fatal in about 5% of patients, the mortality rate
associated with SBO has decreased dramatically over
the past century.
Intrauterine adhesions are relatively common in
women and the majority of women undergoing gynecological surgery develop postoperative adhesions.
Sometimes these pelvic adhesions cause chronic pelvic
pain and/or infertility.
Adhesions can cause a rare form of glaucoma
called irido corneal endothelial (ICE) syndrome. In
this disorder cells from the back surface of the cornea
of the eye spread over the surface of the iris and the
tissue that drains the eye, forming adhesions that bind
the iris to the cornea and causing further blockage of
the drainage channels. This blockage increases the
pressure inside the eye, which may damage the optic
nerve. ICE syndrome occurs most often in lightskinned females.

Causes and symptoms
Post-surgical adhesions
Common causes of postoperative adhesions
include:


abdominal surgery



gynecological surgery



thoracic surgery



orthopedic surgery



plastic surgery.

Abdominal adhesions most often result from surgeries in which the organs are handled or temporarily
moved. Intrauterine adhesions form after surgeries
involving the uterus, particularly curettage—the
scraping of the uterine contents. Surgery to control
uterine bleeding after giving birth also can lead to
intrauterine adhesions. Such adhesions can cause
Asherman’s syndrome, closing the uterus and preventing menstruation.
Other causes of adhesions
Any inflammation or infection of the membranes
that line the abdominal and pelvic walls and enclose
62

the organs—the peritoneum—can cause adhesions.
An example peritonitis, a severe infection that can
result from appendicitis, may lead to adhesions. In
addition to surgery or injury, pelvic adhesions can be
caused by inflammation resulting from an infection
such as pelvic inflammatory disease (PID).
Symptoms
In the majority of people adhesions do not cause
symptoms or serious problems. However in some people adhesions can lead to a variety of disorders. The
symptoms depend on the type of adhesion and the
tissues that are involved. Adhesions may cause pain
and/or fever in some people.
ABDOMINAL OBSTRUCTION. If a loop of intestine
becomes trapped under an adhesion, the intestine may
become partially or completely blocked. The symptoms of intestinal obstruction or SBOs due to adhesions depend on the degree and location of the
obstruction. Partial or off-and-on intestinal obstruction due to adhesions may result in intermittent periods of painful abdominal cramping and other
symptoms, including diarrhea.

Symptoms of significant intestinal obstruction
due to adhesions include:


severe abdominal pain and cramping



nausea and vomiting



abdominal distension (swelling)



constipation and the inability to pass gas



symptoms of dehydration.
Symptoms of dehydration include:



dry mouth and tongue



severe thirst



infrequent urination



dry skin



fast heart rate



low blood pressure.

In about 10% of SBOs, part of the intestine twists
tightly and repeatedly around a band of adhesions,
cutting off the blood supply to the intestine and resulting in strangulation and death of the twisted bowel.
The mortality rate for strangulation of the bowel may
be as high as 37%.
Symptoms of bowel strangulation due to adhesions include:


severe abdominal pain, either cramping or constant
GALE ENCYCLOPEDIA OF MEDICINE

abdominal distension due to the inability to pass
stool and gas



an extremely tender abdomen



signs of systemic (body-wide) illness, including fever,
fast heart rate, and low blood pressure.

When a portion of the obstructed bowel begins to
die from lack of blood flow, fluids and bacteria that
help digest food can leak out of the intestinal wall and
into the abdominal cavity causing peritonitis.
PELVIC ADHESIONS. Pelvic adhesions can interfere
with the functioning of the ovaries and fallopian tubes
and are among the common causes of female infertility. Adhesions on the ovaries or fallopian tubes can
prevent pregnancy by trapping the released egg.
Adhesions resulting from endometriosis can cause pelvic pain, particularly during menstruation, as well as
fertility problems.

Diagnosis
Adhesions are diagnosed based on the symptoms,
surgical history, and a physical examination. The physician examines the abdomen and rectum and performs
a pelvic examination on women. Blood tests and chest
and abdominal x rays are taken. Sometimes exploratory surgery is used to locate the adhesions and
sources of pain.
Abdominal computed axial tomography—a CT
or CAT scan—is the most common diagnostic tool
for SBO and intestinal strangulation due to adhesions.
In this procedure a computer reconstructs a portion
of the abdomen from x-ray scans. Barium contrast
x-ray studies also may be used to locate an obstruction. The ingestion of a barium solution provides better visualization of the abdominal organs. However
sometimes intestinal obstruction or strangulation
cannot be confirmed without abdominal surgery.
Exploratory laparoscopy may be used to detect
either abdominal or pelvic adhesions. This procedure
usually is performed in a hospital under local or general anesthesia. A small incision is made near the naval
and carbon dioxide gas is injected to raise the abdominal wall. A tube called a trocar is inserted into the
abdomen. The laparascope, equipped with a light and
a small video camera, is passed through the trocar
for visualization of the peritoneal cavity and the
abdominal or pelvic organs.
Pelvic adhesions also may be detected by hysteroscopy. In this procedure a uterine endoscope is
inserted through the cervix to visualize the cervix and
uterine cavity. With hysterosalpingography (HSG) a
GALE ENCYCLOPEDIA OF MEDICINE

radiopaque or contrast dye is injected through a catheter in the cervix and x rays are taken of the uterus and
fallopian tubes.

Treatment
Although the symptoms of adhesion disease
sometimes disappear on their own, adhesions are permanent without a surgical procedure called adhesion
lysis to disrupt or remove the tissue.
Abdominal adhesions
Sometimes an adhesion-trapped intestine frees
itself spontaneously. Surgery may be used to reposition the intestine to relieve symptoms. Various other
techniques include using suction to decompress the
intestine; however untreated intestinal adhesions may
lead to bowel obstruction.
Although dilation with an endoscope may be used
to widen the region around an intestinal obstruction to
relieve symptoms, SBOs caused almost always require
immediate surgery. In cases of a partial obstruction or
a complete obstruction without severe symptoms, surgery may be delayed for 12–24 hours so that a dehydrated patient can be treated with intravenous fluids.
A small suction tube may be placed through the nose
into the stomach to remove the stomach contents to
relieve pain and nausea and prevent further bloating.
If an adhesion-related SBO disrupts the blood
supply to part of the intestine, gangrene—tissue
death—can occur. Strangulation of the bowel usually
requires emergency abdominal surgery to remove the
adhesions and restore blood flow to the intestine.
Intestinal obstruction repair is performed under general anesthesia. An incision is made in the abdomen,
the obstruction is located, and the adhesions are cut
away, releasing the intestine. The bowel is examined
for injury or tissue death. If possible, injured and dead
sections are removed and the healthy ends of the intestine are stitched together (resectioned). If resectioning
is not possible, the ends of the intestine are brought
through an opening in the abdomen called an ostomy.
In some cases laparoscopic surgery can be used to
removed damaged portions of the intestines. Five or
six small incisions—0.2–0.4 in. (5–10 mm) in length—
are made in the abdomen. The laparoscope, equipped
with its light and camera, and surgical instruments are
inserted through the incisions. The laparoscope guides
the surgeon by projecting images of the abdominal
organs on a video monitor. However the existence of
multiple adhesions may preclude the use of laparoscopic surgery.
63

Adhesions



Adhesions

Other types of adhesions

can be used to physically separate the tissues after
surgery to prevent the formation of postoperative
adhesions.However these gels and other barrier agents
may:

Adhesions caused by endometriosis may be
removed by either traditional open abdominal or pelvic surgery or by laparoscopic surgery. In the latter
technique the laparoscope includes a laser for destroying the tissue with heat. Although untreated gynecological adhesions can lead to infertility, both types of
surgeries also can result in adhesion formation.



suppress the immune system



cause infection



impair healing

ICE-type glaucoma caused by adhesions is difficult to treat; however untreated ICE syndrome can
lead to blindness. Treatment usually includes medication and/or filtering surgery. Filtering microsurgery
involves cutting a tiny hole in the white of the eye
(the sclera) to allow fluid to drain, thereby lowering
the pressure in the eye and preventing or reducing
damage to the optic nerve.

Systemic anti-inflammatory medications may be
used to help prevent adhesion formation. Recent studies suggest that the common oral arthritis drug,
Celebrex, an anti-inflammatory COX-2 inhibitor,
taken before and immediately after surgery, may
help prevent abdominal adhesions. Celebrex is
known to inhibit both the formation of blood vessels
and fibroblast activity, which are necessary for the
formation of scar tissue.

Alternative treatment
In cases where the intestines are partially blocked
by adhesions, a diet low in fiber—called a low-residue
diet—may enable food to move more easily through
the obstruction.

Prognosis
Intestinal obstruction surgery usually has a favorable outcome if the surgery is performed before tissue
damage or death occurs. Surgery to remove adhesions
and to free or reconnect the intestine often is sufficient
for reducing symptoms and returning normal function
to the intestine or other organ. However the risk of
new adhesion formation increases with each additional surgery. Thus abdominal adhesions can become
a recurring problem. Adhesions reform in 11–21% of
patients who have surgery to remove an adhesionrelated intestinal obstruction. The risk of recurrence
is particularly high among survivors of bowel
strangulation.

Prevention
Abdominal and gynecological laparoscopic surgeries—also known as ‘‘keyhole’’ surgeries—reduce
the size of the incision and the amount of contact
with the organs, thereby lowering the risk of adhesion
formation. Sometimes the intestines are fixed in place
during surgery so as to promote benign adhesions that
will not cause obstructions.
Within five days after surgery the disturbed tissue
surfaces have formed a new lining of mesothelial cells
that prevent adhesions from forming. Therefore biodegradable barrier membranes, films, gels, or sprays
64

Recent research has focused on the incorporation
of anti-inflammatory and anti-proliferation drugs into
polymeric films used for preventing and treating postsurgical adhesions. New types of gels to prevent postoperative adhesions also are under development.
Resources
BOOKS

Baerga-Varela, Y. ‘‘Small Bowel Obstruction.’’ Mayo Clinic
Gastrointestinal Surgery, edited by K. A. Kelly, et al.
St. Louis, MO: Elsevier Science, 2004.
PERIODICALS

‘‘Surgical Complications; Celebrex Prevents Adhesions
After Surgery.’’ Science Letter (February 15, 2005):
1443.
ORGANIZATIONS

National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. 800-8915389. 301-654-3810. <http://digestive.niddk.nih.gov/>.
OTHER

Abdominal Adhesions. Aetna InteliHealth. February 17,
2004 [cited March 2, 2005]. <http://www.intelihealth.
com/IH/ihtIH/WSIHW000/9339/9394.html>.
Endometriosis. MayoClinic.com. September 11, 2003 [cited
March 2, 2005]. <http://www.mayoclinic.com>.
Infertility. MayoClinic.com. September 21, 2004 [cited
March 2, 2005]. <http://www.mayoclinic.com/
invoke.cfm?id=DS00289>.
‘‘Intestinal Adhesions.’’ Digestive Diseases. National
Digestive Diseases Information Clearinghouse.
February 2004 [cited February 21, 2005]. <http://
digestive.niddk.nih.gov/ddiseases/pubs/intestinaladhe
sions/index.htm>.
What is Glaucoma? Glaucoma Research Foundation. [Cited
March 4, 2005]. <http://www.glaucoma.org/learn/>.

Margaret Alic, Ph.D.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Definition

Multiple sclerosis—A progressive disorder of the
central nervous system in which scattered patches
of the protective sheath covering the nerves is
destroyed. The disease, which causes progressive
paralysis, is marked by periods of exacerbation and
remission. There is no cure.

An adjustment disorder is a debilitating reaction,
usually lasting less than six months, to a stressful event
or situation. It is not the same thing as post-traumatic
stress disorder (PTSD), which usually occurs in reaction to a life-threatening event and can be longer
lasting.

Post-traumatic stress disorder (PTSD)—A specific
form of anxiety that begins after a life-threatening
event, such as rape, a natural disaster, or combatrelated trauma.

Description
An adjustment disorder usually begins within
three months of a stressful event, and ends within six
months after the stressor stops. There are many different subtypes of adjustment disorders, including
adjustment disorder with:



crying



anxiety



depression



worry



anxiety



headaches or stomachaches



mixed anxiety and depression



withdrawal



conduct disturbances



inhibition



mixed disturbance of emotions and conduct



truancy



unspecified



vandalism



reckless driving



fighting



other destructive acts

Adjustment disorders are very common and can
affect anyone, regardless of gender, age, race, or lifestyle. By definition, an adjustment disorder is shortlived, unless a person is faced with a chronic recurring
crisis (such as a child who is repeatedly abused). In
such cases, the adjustment disorder may last more
than six months.

Causes and symptoms
An adjustment disorder occurs when a person
can’t cope with a stressful event and develops emotional or behavioral symptoms. The stressful event can
be anything: it might be just one isolated incident, or a
string of problems that wears the person down. The
stress might be anything from a car accident or illness,
to a divorce, or even a certain time of year (such as
Christmas or summer).
People with adjustment disorder may have a wide
variety of symptoms. How those symptoms combine
depend on the particular subtype of adjustment disorder and on the individual’s personality and psychological defenses. Symptoms normally include some
(but not all) of the following:


hopelessness



sadness

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
It is extremely important that a thorough evaluation rule out other more serious mental disorders,
since the treatment for adjustment disorder may be
very different than for other mental problems.
In order to be diagnosed as a true adjustment
disorder, the level of distress must be more severe
than what would normally be expected in response to
the stressor, or the symptoms must significantly interfere with a person’s social, job, or school functioning.
Normal expression of grief, in bereavement for
instance, is not considered an adjustment disorder.

Treatment
Psychotherapy (counseling) is the treatment of
choice for adjustment disorders, since the symptoms
are an understandable reaction to a specific stress. The
type of therapy depends on the mental health expert,
but it usually is short-term treatment that focuses on
resolving the immediate problem.
65

Adjustment disorders

I Adjustment disorders

Adrenal gland cancer

Therapy usually will help clients:


develop coping skills



understand how the stressor has affected their lives



develop alternate social or recreational activities

Family or couples therapy may be helpful in some
cases. Medications are not usually used to treat adjustment disorders, although sometimes a few days or
weeks of an anti-anxiety drug can control anxiety or
sleeping problems.
Self-help groups aimed at a specific problem (such
as recovering from divorce or job loss) can be extremely helpful to people suffering from an adjustment
disorder. Social support, which is usually an important part of self-help groups, can lead to a quicker
recovery.

Prognosis
Most people recover completely from adjustment
disorders, especially if they had no previous history of
mental problems, and have a stable home life with
strong social support. People with progressive or cyclic
disorders (such as multiple sclerosis) may experience an
adjustment disorder with each exacerbation period.
Resources

When tumors develop in the adrenal gland, they
secrete excess amounts of these hormones. A cancer
that arises in the adrenal cortex is called an adrenocortical carcinoma and can produce high blood pressure, weight gain, excess body hair, weakening of the
bones and diabetes. A cancer in the adrenal medulla is
called a pheochromocytoma and can cause high blood
pressure, headache, palpitations, and excessive perspiration. Although these cancers can happen at any
age, most occur in young adults.

Causes and symptoms
It is not known what causes adrenal gland cancer,
but some cases are associated with hereditary diseases.
Symptoms of adrenal cancer are related to the specific
hormones produced by that tumor. An adrenocortical
carcinoma typically secretes high amounts of cortisol,
producing Cushing’s Syndrome. This syndrome produces progressive weight gain, rounding of the face,
and increased blood pressure. Women can experience
menstrual cycle alterations and men can experience
feminization. The symptoms for pheochromocytoma
include hypertension, acidosis, unexplained fever and
weight loss. Because of the hormones produced by this
type of tumor, anxiety is often a feature also.

Diagnosis

BOOKS

Luther, Suniya G., Jacob A. Burack, and Dante Cicchetti.
Developmental Psychopathology: Perspectives on
Adjustment, Risk, and Disorder. London: Cambridge
University Press, 1997.

Carol A. Turkington

Diagnosis for adrenal cancer usually begins with
blood tests to evaluate the hormone levels. These hormones include epinephrine, cortisol, and testosterone.
It also includes magnetic resonance imaging, and computed tomography scans to determine the extent of the
disease. Urine and blood tests can be done to detect
the high levels of hormone secreted by the tumor.

Treatment

I Adrenal gland cancer
Definition
Adrenal gland cancers are rare cancers occuring in
the endocrine tissue of the adrenals. They are characterized by overproduction of adrenal gland hormones.

Description
Cancers of the adrenal gland are very rare. The
adrenal gland is a hormone producing endocrine gland
with two main parts, the cortex and the medulla. The
main hormone of the adrenal cortex is cortisol and the
main hormone of the adrenal medulla is epinephrine.
66

Treatment is aimed at removing the tumor by
surgery. In some cases, this can be done by laparoscopy. Surgery is sometimes followed by chemotherapy
and/or radiation therapy. Because the surgery removes
the source of many important hormones, hormones
must be supplemented following surgery. If adrenocortical cancer recurs or has spread to other parts of
the body (metastasized), additional surgery may be
done followed by chemotherapy using the drug
mitotane.

Alternative treatment
As with any form of cancer, all conventional treatment options should be considered and applied as
GALE ENCYCLOPEDIA OF MEDICINE

Cortisol—A hormone produced by the adrenal cortex. It is partially responsible for regulating blood
sugar levels.
Diabetes—A disease characterized by low blood
sugar.
Epinephrine—A hormone produced by the adrenal
medulla. It is important in the response to stress and
partially regulates heart rate and metabolism. It is
also called adrenaline.
Laparoscopy—The insertion of a tube through
the abdominal wall. It can be used to visualize
the inside of the abdomen and for surgical
procedures.

appropriate. Nutritional support, as well as supporting the functioning of the entire person diagnosed with
adrenal gland cancer through homeopathic medicine,
acupuncture, vitamin and mineral supplementation,
and herbal medicine, can benefit recovery and enhance
quality of life.

I Adrenal gland scan
Definition
The adrenal gland scan is a nuclear medicine evaluation of the medulla (inner tissue) of the adrenal
gland.

Purpose
The adrenal glands are a pair of small organs
located just above the kidney, which contain two
types of tissue. The adrenal cortex produces hormones
that affect water balance and metabolism in the body.
The adrenal medulla produces adrenaline and noradrenaline (also called epinepherine and norepinepherine).
An adrenal gland scan is done when too much
adrenaline and noradrenaline is produced in the
body and a tumor in the adrenal gland is suspected.
One such situation in which a tumor might be suspected is when high blood pressure (hypertension)
does not respond to medication. Tumors that secrete
adrenaline and noradrenaline can also be found outside the adrenal gland. An adrenal gland scan usually
covers the abdomen, chest, and head.

Precautions

Prognosis
The prognosis for adrenal gland cancer is variable. For localized pheochromocytomas the 5-year
survival rate is 95%. This rate decreases with aggressive tumors that have metastasized. The prognosis for
adrenal cortical cancer is not as good with a 5-year
survival rate of 10-35%.

Prevention
Since so little is known about the cause of adrenal
gland cancer, it is not known if it can be prevented.

Adrenal gland scans are not recommended for
pregnant women because of the potential harm to
the developing fetus. A pregnant woman should discuss with her doctor the risks of the procedure against
the benefits of the information it can provide in evaluating her individual medical situation.
People who have recently undergone tests that use
barium must wait until the barium has been eliminated
from their system in order to obtain accurate results
from the adrenal gland scan.

Description

Resources
BOOKS

Norton, J. A. ‘‘Adrenal Tumors.’’ In Cancer, Principles and
Practice of Oncology, edited by V. T. DeVita,
S. Hellman, and S. A. Rosenberg. Philadelphia:
Lippincott-Raven, 1997.
OTHER

Endocrine Web. <http://www.endocrineweb.com>.

Cindy L. A. Jones, PhD

Adrenal gland removal see Adrenalectomy
GALE ENCYCLOPEDIA OF MEDICINE

The adrenal gland scan takes several days. On the
first day, a radiopharmaceutical is injected intravenously into the patient. On the second, third, and
fourth day the patient is positioned under the camera
for imaging. The scanning time each day takes
approximately 30 minutes. It is essential that the
patient remain still during imaging.
Occasionally, the scanning process may involve
fewer than three days, or it may continue several
days longer. The area scanned extends from the pelvis
and lower abdomen to the lower chest. Sometimes the
upper legs, thighs, and head are also included.
67

Adrenal gland scan

KEY TERMS

Adrenal virilism

Adrenal hypofunction see Addison’s disease

KEY TERMS
Adrenal cortex—The outer tissue of the adrenal
gland. It produces a group of chemically related
hormones called corticosteroids that control
mineral and water balance in the body and include
aldosterone and cortisol.
Adrenal medulla—The inner tissue of the adrenal
gland. It produces the hormones adrenaline and
noradrenaline.
Lugol’s solution—A strong iodine solution.

Preparation
For two days before and ten days after the injection of the radiopharmaceutical, patients are given
either Lugol’s solution or potassium iodine. This prevents the thyroid from taking up radioactive iodine
and interfering with the scan.

Aftercare
The patient should not feel any adverse effects of
the test and can resume normal activity immediately.
Follow-up tests that might be ordered include a
nuclear scan of the bones or kidney, a computed
tomography scan (CT) of the adrenals, or an ultrasound of the pelvic area.

Adrenal insufficiency see Addison’s disease

I Adrenal virilism
Definition
Adrenal virilism is the development or premature
development of male secondary sexual characteristics
caused by male sex hormones (androgens) excessively
produced by the adrenal gland. This disorder can
occur before birth and can lead to sexual abnormalities in newborns. It can also occur in girls and women
later in life.

Description
In the normal human body, there are two adrenal
glands. They are small structures that lie on top of the
kidneys. The adrenal glands produce many hormones
that regulate body functions. These hormones include
androgens, or male hormones. Androgens are produced in normal girls and women. Sometimes, one or
both of the adrenal glands becomes enlarged or overactive, producing more than the usual amount of
androgens. The excess androgens create masculine
characteristics.

Risks
The main risk associated with this test is to the
fetus of a pregnant woman.

Normal results
Normal results will show no unusual areas of
hormone secretion and no tumors.

Abnormal results
Abnormal results will show evidence of a tumor
where there is excessive secretion of adrenaline or
noradrenaline. Over 90% of these tumors are in the
abdomen.
Resources
BOOKS

Fishback, Francis, editor. A Manual of Laboratory and
Diagnostic Tests. 5th ed. Philadelphia: Lippincott, 1996.

Tish Davidson, A.M.
68

Causes and symptoms
In infants and children, adrenal virilism is usually
the result of adrenal gland enlargement that is present
at birth. This is called congenital adrenal hyperplasia.
The cause is usually a genetic problem that leads to
severe enzyme deficiencies. In rare cases, adrenal
virilism is caused by an adrenal gland tumor. The
tumor can be benign (adrenal adenoma) or cancerous
(adrenal carcinoma). Sometimes virilism is caused by a
type of tumor on a woman’s ovary (arrhenoblastoma).
Newborn girls with adrenal virilism have external
sex organs that seem to be a mixture of male and
female organs (called female pseudohermaphrodism).
Newborn boys with the disorder have enlarged external sex organs, and these organs develop at an abnormally rapid pace.
Children with congenital adrenal hyperplasia begin
growing abnormally fast, but they stop growing earlier
than normal. Later in childhood, they are typically
shorter than normal but have well-developed trunks.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Endocrinologists, doctors who specialize in the
diagnosis and treatment of glandular disorders, have
the most expertise to deal with adrenal virilization.
Some doctors who treat disorders of the internal
organs (internists) and doctors who specialize in treating the reproductive system of women (gynecologists)
may also be able to help patients with this disorder.
Diagnosis involves performing many laboratory
tests on blood samples from the patient. These tests
measure the concentration of different hormones.
Different abnormalities of the adrenal gland produce
a different pattern of hormonal abnormalities. These
tests can also help determine if the problem is adrenal
or ovarian. If a tumor is suspected, special x rays may
be done to visualize the tumor in the body. Final
diagnosis may depend on obtaining a tissue sample
from the tumor (biopsy), and examining it under a
microscope in order to verify its characteristics.

KEY TERMS
Glucocorticoid—A hormone produced by the
adrenal gland; this hormone leads to an increase
in blood sugar and creation of sugar molecules by
the liver.
Hydrocortisone—A hormone in the group of glucocorticoid hormones.
Prednisone—A drug that functions as a glucocorticoid hormone.

but there is no cure. If a cancerous tumor has caused
the disorder, patients have a better prognosis if they
have an early stage of cancer that is diagnosed quickly
and has not spread.
Resources
PERIODICALS

Willensy, D. ‘‘The Endocrine System.’’ AmericanHealth
April 1996: 92-3.

Richard H. Lampert

Treatment
Adrenal virilism caused by adrenal hyperplasia is
treated with daily doses of a glucocorticoid. Usually
prednisone is the drug of choice, but in infants hydrocortisone is usually given. Laboratory tests are usually
needed from time to time to adjust the dosage. Girls
with pseudohermaphrodism may require surgery to
make their external sex organs appear more normal.
If a tumor is causing the disorder, the treatment will
depend on the type and location of the tumor.
Information about the tumor cell type and the spread
of the tumor is used to decide the best kind of treatment
for a particular patient. If the tumor is cancerous, the
patient will require special treatment depending on how
far the cancer has advanced. Treatment can be a combination of surgery, medications used to kill cancer cells
(chemotherapy), and x rays or other high energy rays
used to kill cancer cells (radiation therapy). Sometimes
the doctor must remove the adrenal gland and the
surrounding tissues. If the tumor is benign, then surgically removing the tumor may be the best option.

Prognosis
Ongoing glucocorticoid treatment usually controls adrenal virilism in cases of adrenal hyperplasia,
GALE ENCYCLOPEDIA OF MEDICINE

I Adrenalectomy
Definition
Adrenalectomy is the surgical removal of one or
both of the adrenal glands. The adrenal glands are
paired endocrine glands, one located above each kidney, that produce hormones such as epinephrine, norepinephrine, androgens, estrogens, aldosterone, and
cortisol. Adrenalectomy is usually performed by conventional (open) surgery, but in selected patients surgeons may use laparoscopy. With laparoscopy,
adrenalectomy can be accomplished through four
very small incisions.

Purpose
Adrenalectomy is usually advised for patients
with tumors of the adrenal glands. Adrenal gland
tumors may be malignant or benign, but all typically
excrete excessive amounts of one or more hormones. A
successful procedure will aid in correcting hormone
imbalances, and may also remove cancerous tumors
that can invade other parts of the body. Occasionally,
adrenalectomy may be recommended when hormones
69

Adrenalectomy

Women with adrenal virilization may develop
facial hair. Typically, their menstrual cycles are infrequent or absent. They may also develop a deeper
voice, a more prominent Adam’s apple, and other
masculine signs.

Adrenalectomy

produced by the adrenal glands aggravate another
condition such as breast cancer.

Precautions
The adrenal glands are fed by numerous blood
vessels, so surgeons need to be alert to extensive bleeding during surgery. In addition, the adrenal glands lie
close to one of the body’s major blood vessels (the
vena cava), and to the spleen and the pancreas. The
surgeon needs to remove the gland(s) without damaging any of these important and delicate organs.

Description
Open adrenalectomy
The surgeon may operate from any of four directions, depending on the exact problem and the
patient’s body type.
In the anterior approach, the surgeon cuts into the
abdominal wall. Usually the incision will be horizontal, just under the rib cage. If the surgeon intends to
operate on only one of the adrenal glands, the incision
will run under just the right or the left side of the rib
cage. Sometimes a vertical incision in the middle of the
abdomen provides a better approach, especially if
both adrenal glands are involved.
In the posterior approach, the surgeon cuts into
the back, just beneath the rib cage. If both glands are
to be removed, an incision is made on each side of the
body. This approach is the most direct route to the
adrenal glands, but it does not provide quite as clear a
view of the surrounding structures as the anterior
approach.
In the flank approach, the surgeon cuts into the
patient’s side. This is particularly useful in massively
obese patients. If both glands need to be removed, the
surgeon must remove one gland, repair the surgical
wound, turn the patient onto the other side, and repeat
the entire process.
The last approach involves an incision into the
chest cavity, either with or without part of the incision
into the abdominal cavity. It is used when the surgeon
anticipates a very large tumor, or if the surgeon needs
to examine or remove nearby structures as well.
Laparoscopic adrenalectomy
This technique does not require the surgeon to
open the body cavity. Instead, four small incisions
(about 1/2 in diameter each) are made into a patient’s
flank, just under the rib cage. A laparoscope, which
enables the surgeon to visualize the inside of the
70

KEY TERMS
Laparoscope—An instrument that enables the surgeon to see inside the abdominal cavity by means
of a thin tube that carries an image to a television
monitor.
Pancreas—An organ that secretes a number of
digestive hormones and also secretes insulin to
regulate blood sugar.
Pheochromocytoma—A tumor of specialized cells
of the adrenal gland.
Spleen—An organ that traps and breaks down red
blood cells at the end of their useful life and manufactures some key substances used by the immune
system.
Vena cava—The large vein that drains directly into
the heart after gathering incoming blood from the
entire body.

abdominal cavity on a television monitor, is placed
through one of the incisions. The other incisions are
for tubes that carry miniaturized versions of surgical
tools. These tools are designed to be operated by
manipulations that the surgeon makes outside the
body.

Preparation
Most aspects of preparation are the same as in
other major operations. In addition, hormone imbalances are often a major challenge. Whenever possible,
physicians will try to correct hormone imbalances
through medication in the days or weeks before surgery. Adrenal tumors may cause other problems such
as hypertension or inadequate potassium in the blood,
and these problems also should be resolved if possible
before surgery is performed. Therefore, a patient may
take specific medicines for days or weeks before
surgery.
Most adrenal tumors can be imaged very well with
a CT scan or MRI, and benign tumors tend to look
different on these tests than do cancerous tumors.
Surgeons may order a CT scan, MRI, or scintigraphy
(viewing of the location of a tiny amount of radioactive agent) to help locate exactly where the tumor is.
The day before surgery, patients will probably
have an enema to clear the bowels. In patients with
lung problems or clotting problems, physicians may
advise special preparations.
GALE ENCYCLOPEDIA OF MEDICINE

Patients stay in the hospital for various lengths of
time after adrenalectomy. The longest hospital stays
are required for open surgery using an anterior
approach; hospital stays of about three days are indicated for open surgery using the posterior approach or
for laparoscopic adrenalectomy.
The special concern after adrenalectomy is the
patient’s hormone balance. There may be several sets
of lab tests to define hormone problems and monitor
the results of drug treatment. In addition, blood pressure problems and infections are more common after
removal of certain types of adrenal tumors.
As with most open surgery, surgeons are also
concerned about blood clots forming in the legs and
traveling to the lungs (venous thromboembolism),
bowel problems, and postoperative pain. With laparoscopic adrenalectomy, these problems are somewhat
less difficult, but they are still present.

I Adrenocorticotropic
hormone
test
Definition
Adrenocorticotropic hormone test (also known as
an ACTH test or a corticotropin test) measures pituitary gland function.

Purpose
The pituitary gland produces the hormone
ACTH, which stimulates the outer layer of the adrenal
gland (the adrenal cortex). ACTH causes the release of
the hormones hydrocortisone (cortisol), aldosterone,
and androgen. The most important of these hormones
released is cortisol. The ACTH test is used to determine if too much cortisol is being produced (Cushing’s
syndrome) or if not enough cortisol is being produced
(Addison’s disease).

Precautions

Risks
The special risks of adrenalectomy involve major
hormone imbalances, caused by the underlying disease, the surgery, or both.These can include problems
with wound healing itself, blood pressure fluctuations,
and other metabolic problems.
Other risks are typical of many operations.These
include:


bleeding



damage to adjacent organs (spleen, pancreas)



loss of bowel function



blood clots in the lungs



lung problems



surgical infections



pain



extensive scarring

ACTH has diurnal variation, meaning that the
levels of this hormone vary according to the time of
day. The highest levels occur in the morning hours.
Testing for normal secretion, as well as for Cushing’s
disease, may require multiple samples. For sequential
follow-up, a blood sample analyzed for ACTH should
always be drawn at the same time each day.
ACTH can be directly measured by an analyzing
method (immunoassay) in many large laboratories.
However, smaller laboratories are usually not
equipped to perform this test and they may need to
send the blood sample to a larger laboratory. Because
of this delay, results may take several days to obtain.

Description

Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

Richard H. Lampert

ACTH production is partly controlled by an area
in the center of the brain (the hypothalamus) and partly
controlled by the level of cortisol in the blood. When
ACTH levels are too high, cortisol production increases
to suppress ACTH release from the pituitary gland. If
ACTH levels are too low, the hypothalamus produces
corticotropin-releasing hormone (CRH) to stimulate
the pituitary gland to make more ACTH. ACTH levels
rise in response to stress, emotions, injury, infection,
burns, surgery, and decreased blood pressure.
Cushing’s syndrome

Adrenocortical insufficiency see Addison’s
disease
GALE ENCYCLOPEDIA OF MEDICINE

Cushing’s syndrome is caused by an abnormally
high level of circulating hydrocortisone. The high level
71

Adrenocorticotropic hormone test

Aftercare

Adrenoleukodystrophy

KEY TERMS
Adrenal glands—A pair of endocrine glands that lie
on top of the kidneys.
Pituitary gland—The most important of the endocrine glands, glands that release hormones directly
into the bloodstream; sometimes called the master
gland.

may be the result of an adrenal gland tumor or enlargement of both adrenal glands due to a pituitary
tumor. The high level of hydrocortisone may be the
result of taking corticosteroid drugs for a long time.
Corticosteroid drugs are widely used for inflammation
in disorders like rheumatoid arthritis, inflammatory
bowel disease, and asthma.
Addison’s disease
Addison’s disease is a rare disorder in which
symptoms are caused by a deficiency of hydrocortisone and aldosterone. The most common cause of
this disease is an autoimmune disorder. The immune
system normally fights foreign invaders in the body
like bacteria. In an autoimmune disorder, the
immune systems attacks the body. In this case, the
immune system produces antibodies that attack
the adrenal glands. Addison’s disease generally progresses slowly, with symptoms developing gradually
over months or years. However, acute episodes,
called Addisonian crises, are brought on by infection,
injury, or other stresses. Diagnosis is generally made
if the patient fails to respond to an injection of
ACTH, which normally stimulates the secretion of
hydrocortisone.

Preparation
A person’s ACTH level is determined from a
blood sample. The patient must fast from midnight
until the test the next morning. This means that the
patient cannot eat or drink anything after midnight
except water. The patient must also avoid radioisotope scanning tests or recently administered radioisotopes prior to the blood test.

Risks
The risks associated with this test are minimal.
They may include slight bleeding from the location
where the blood was drawn. The patient may feel faint
or lightheaded after the blood is drawn. Sometimes
72

the patient may have an accumulation of blood
under the puncture site (hematoma) after the test.

Normal results
Each laboratory will have its own set of normal
values for this test. The normal values can range from:
Morning (4-8 A.M.) 8-100 pg/mL or 10-80 ng/L (SI
units) Evening (8-10 P.M.) less than 50 pg/mL or less
than 50 ng/L (SI units)

Abnormal results
In Cushing’s syndrome, high levels of ACTH may
be caused by ACTH-producing tumors. These tumors
may be either in the pituitary or in another area (like
tumors from lung cancer or ovarian cancer). Low
ACTH levels may be caused by adrenal enlargement
due to high levels of cortisol and feedback to the
pituitary.
In Addison’s disease, high levels of ACTH may be
caused by adrenal gland diseases. These diseases
decrease adrenal hormones and the pituitary attempts
to increase functioning. Low levels of ACTH may
occur because of decreased pituitary function.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnosticand
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Adrenogenital syndrome see Adrenal
virilism

I Adrenoleukodystrophy
Definition
Adrenoleukodystrophy is a rare genetic disease
characterized by a loss of myelin surrounding nerve
cells in the brain and progressive adrenal gland
dysfunction.

Description
Adrenoleukodystrophy (ALD) is a member of a
group of diseases, leukodystrophies, that cause damage
to the myelin sheath of nerve cells. Approximately one
in 100,000 people is affected by ALD. There are three
GALE ENCYCLOPEDIA OF MEDICINE

The adult-onset form of the disease, also called
adrenomyeloneuropathy, is milder, progresses slowly,
is usually associated with a normal life span, and
usually appears between ages 21-35. Symptoms may
include progressive stiffness, weakness, or paralysis of
the lower limbs and loss of coordination. Brain function deterioration may also been seen. Women who
are carriers of the disease occasionally experience the
same symptoms, as well as others, including ataxia,
hypertonia (excessive muscle tone), mild peripheral
neuropathy, and urinary problems. The neonatal
form affects both male and female infants and may
produce mental retardation, facial abnormalities, seizures, retinal degeneration, poor muscle tone,
enlarged liver, and adrenal dysfunction. Neonatal
ALD usually progresses rapidly.

Causes and symptoms
The genetic defect in ALD causes a decrease in the
ability to degrade very long chain fatty acids. These
build up in the adrenal glands, brain, plasma, and
fibroblasts. The build-up of very long chain fatty
acids interferes with the ability of the adrenal gland
to convert cholesterol into steroids and causes demyelination of nerves in the white matter of the brain.
Demyelinated nerve cells are unable to function
properly.

KEY TERMS
Amniocentesis—The collection of amniotic fluid
through a needle inserted through the abdomen.
Used to collect fetal cells for genetic analysis.
Ataxia—Loss of coordination of muscular movement.
Hypertonia—Having excessive muscular tone.
Myelin—A layer that encloses nerve cells and some
axons and is made largely of lipids and lipoproteins.
Neuropathy—A disease or abnormality of the peripheral nerves.

Treatment
Treatment for all forms of ALD consists of treating the symptoms and supporting the patient with
physical therapy, psychological counseling, and special education in some cases. There is no cure for this
disease, and there are no drugs that can reverse demyelination of nerve and brain cells. Dietary measures
consist of reducing the intake of foods high in fat,
which are a source of very long chain fatty acids. A
mixture called Lorenzo’s Oil has been shown to reduce
the level of long chain fatty acids if used long term;
however, the rate of myelin loss is unaffected.
Experimental bone marrow transplantation has not
been very effective.

Prognosis
Prognosis for childhood and neonatal ALD
patients is poor because of the progressive myelin
degeneration. Death usually occurs between one and
ten years after onset of symptoms.

Prevention
Since ALD is a genetic disease, prevention is largely limited to genetic counseling and fetal monitoring
through amniocentesis or chorionic villus sampling.
Resources

Diagnosis
Diagnosis is made based on observed symptoms, a
biochemical test, and a family history. The biochemical test detects elevated levels of very long chain fatty
acids in samples from amniocentesis, chorionic villi,
plasma, red blood cells, or fibroblasts. A family history may indicate the likelihood of ALD because the
disease is carried on the X-chromosome by the female
lineage of families.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Berkow, Robert. Merck Manual of Medical Information.
Whitehouse Station, NJ: Merck Research
Laboratories, 1997.

John T. Lohr, PhD

Adrenomyeloneuropathy see
Adrenoleukodystrophy
73

Adrenoleukodystrophy

basic forms of ALD: childhood, adult-onset, and
neonatal. The childhood form of the disease is the
classical form and is the most severe. Childhood
ALD is progressive and usually leads to total disability or death. It affects only boys because the genetic
defect is sex-linked (carried on the X chromosome).
Onset usually occurs between ages four and ten and
can include many different symptoms, not all of
which appear together. The most common symptoms
are behavioral problems and poor memory. Other
symptoms frequently seen are loss of vision, seizures,
poorly articulated speech, difficulty swallowing,
deafness, problems with gait and coordination, fatigue, increased skin pigmentation, and progressive
dementia.

Adult respiratory distress syndrome

I Adult
respiratory distress
syndrome

KEY TERMS
Alveoli—The tiny air sacs at the ends of the breathing tubes of the lung where oxygen normally is
taken up by the capillaries to enter the circulation.
Aspiration—The process in which solid food,
liquids, or secretions that normally are swallowed
are, instead, breathed into the lungs.

Definition
Adult respiratory distress syndrome (ARDS), also
called acute respiratory distress syndrome, is a type
of lung (pulmonary) failure that may result from any
disease that causes large amounts of fluid to collect
in the lungs. ARDS is not itself a specific disease, but a
syndrome, a group of symptoms and signs that
make up one of the most important forms of lung or
respiratory failure. It can develop quite suddenly in
persons whose lungs have been perfectly normal.
Very often ARDS is a true medical emergency. The
basic fault is a breakdown of the barrier, or membrane, that normally keeps fluid from leaking out of
the small blood vessels of the lung into the breathing
sacs (the alveoli).

Capillaries—The smallest arteries which, in the
lung, are located next to the alveoli so that they
can pick up oxygen from inhaled air.
Face mask—The simplest way of delivering a high
level of oxygen to patients with ARDS or other lowoxygen conditions.
Steroids—A class of drugs resembling normal body
substances that often help control inflammation in
the body tissues.
Ventilator—A mechanical device that can take
over the work of breathing for a patient whose
lungs are injured or are starting to heal.

Description
Another name for ARDS is shock lung. Its formal
name is misleading, because children, as well as adults,
may be affected. In the lungs the smallest blood vessels, or capillaries, make contact with the alveoli, tiny
air sacs at the tips of the smallest breathing tubes (the
bronchi). This is the all-important site where oxygen
passes from air that is inhaled to the blood, which
carries it to all parts of the body. Any form of lung
injury that damages this point of contact, called the
alveolo-capillary junction, will allow blood and tissue
fluid to leak into the alveoli, eventually filling them so
that air cannot enter. The result is the type of breathing distress called ARDS. ARDS is one of the major
causes of excess fluid in the lungs, the other being heart
failure.
Along with fluid there is a marked increase in
inflamed cells in the lungs. There also is debris left
over from damaged lung cells, and fibrin, a semisolid material derived from blood in the tissues.
Typically these materials join together with large
molecules in the blood (proteins), to form hyaline
membranes. (These membranes are very prominent
in premature infants who develop respiratory distress
syndrome; it is often called hyaline membrane disease.) If ARDS is very severe or lasts a long time, the
lungs do not heal, but rather become scarred, a process
known as fibrosis. The lack of a normal amount of
oxygen causes the blood vessels of the lung to become
narrower, and in time they, too, may become scarred
and filled with clotted blood. The lungs as a whole
become very ‘‘stiff,’’ and it becomes much harder for
the patient to breathe.
74

Causes and symptoms
A very wide range of diseases or toxic substances,
including some drugs, can cause ARDS. They include:


Breathing in (aspiration) of the stomach contents
when regurgitated, or salt water or fresh water from
nearly drowning.



Inhaling smoke, as in a fire; toxic materials in the air,
such as ammonia or hydrocarbons; or too much
oxygen, which itself can injure the lungs.



Infection by a virus or bacterium, or sepsis, a widespread infection that gets into the blood.



Massive trauma, with severe injury to any part of the
body.



Shock with persistently low blood pressure may not
in itself cause ARDS, but it can be an important
factor.



A blood clotting disorder called disseminated intravascular coagulation, in which blood clots form in
vessels throughout the body, including the lungs.



A large amount of fat entering the circulation and
traveling to the lungs, where it lodges in small blood
vessels, injuring the cells lining the vessel walls.



An overdose of a narcotic drug, a sedative, or, rarely,
aspirin.
GALE ENCYCLOPEDIA OF MEDICINE

Inflammation of the pancreas (pancreatitis), when
blood proteins, called enzymes, pass to the lungs
and injure lung cells.



Severe burn injury.



Injury of the brain, or bleeding into the brain, from
any cause may be a factor in ARDS for reasons that
are not clear. Convulsions also may cause some
cases.

Usually ARDS develops within one to two days of
the original illness or injury. The person begins to take
rapid but shallow breaths. The doctor who listens to
the patient’s chest with a stethoscope may hear
‘‘crackling’’ or wheezing sounds. The low blood oxygen content may cause the skin to appear mottled or
even blue. As fluid continues to fill the breathing sacs,
the patient may have great trouble breathing, take
very rapid breaths, and gasp for air.

Diagnosis
A simple test using a device applied to the ear will
show whether the blood is carrying too little oxygen,
and this can be confirmed by analyzing blood taken
from an artery. The chest x ray may be normal in the
early stages, but, in a short time, fluid will be seen
where it does not belong. The two lungs are about
equally affected. A heart of normal size indicates that
the problem actually is ARDS and not heart failure.
Another way a physician can distinguish between
these two possibilities is to place a catheter into a
vein and advance it into the main artery of the lung.
In this way, the pressure within the pulmonary capillaries can be measured. Pressure within the pulmonary
capillaries is elevated in heart failure, but normal
in ARDS.

Treatment
The three main goals in treating patients with
ARDS are:


To treat whatever injury or disease has caused
ARDS. Examples are: to treat septic infection with
the proper antibiotics, and to reduce the level of
oxygen therapy if ARDS has resulted from a toxic
level of oxygen.



To control the process in the lungs that allows fluid
to leak out of the blood vessels. At present there
is no certain way to achieve this. Certain steroid
hormones have been tried because they can combat
inflammation, but the actual results have been
disappointing.

GALE ENCYCLOPEDIA OF MEDICINE



To make sure the patient gets enough oxygen until
the lung injury has had time to heal. If oxygen delivered by a face mask is not enough, the patient is
placed on a ventilator, which takes over breathing,
and, through a tube placed in the nose or mouth (or
an incision in the windpipe), forces oxygen into the
lungs. This treatment must be closely supervised, and
the pressure adjusted so that too much oxygen is not
delivered.

Patients with ARDS should be cared for in an
intensive care unit, where experienced staff and all
needed equipment are available. Enough fluid must
be provided, by vein if necessary, to prevent dehydration. Also, the patient’s nutritional state must be maintained, again by vein, if oral intake is not sufficient.

Prognosis
If the patient’s lung injury does not soon begin to
heal, the lack of sufficient oxygen can injure other
organs, such as the kidneys. There always is a risk
that bacterial pneumonia will develop at some point.
Without prompt treatment, as many as 90% of
patients with ARDS can be expected to die. With
modern treatment, however, about half of all patients
will survive. Those who do live usually recover completely, with little or no long-term breathing difficulty.
Lung scarring is a risk after a long period on a ventilator, but it may improve in the months after the
patient is taken off ventilation. Whether a particular
patient will recover depends to a great extent on
whether the primary disease that caused ARDS to
develop in the first place can be effectively treated.

Prevention
The only way to prevent ARDS is to avoid those
diseases and harmful conditions that damage the lung.
For instance, the danger of aspirating stomach contents into the lungs can be avoided by making sure a
patient does not eat shortly before receiving general
anesthesia. If a patient needs oxygen therapy, as low a
level as possible should be given. Any form of lung
infection, or infection anywhere in the body that gets
into the blood, must be treated promptly to avoid the
lung injury that causes ARDS.
Resources
BOOKS

Smolley, Lawrence A., and Debra F. Bryse. Breathe
RightNow: A Comprehensive Guide to Understanding
and Treating the Most Common Breathing Disorders.
New York: W. W. Norton & Co., 1998.

75

Adult respiratory distress syndrome



Aging

ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Respiratory Distress Syndrome Foundation. P.O.
Box 723, Montgomeryville, PA 18936.



Hearing, which declines especially in relation to the
highest pitched tones.



The proportion of fat to muscle, which may increase
by as much as 30%. Typically, the total padding of
body fat directly under the skin thins out and accumulates around the stomach. The ability to excrete
fats is impaired, and therefore the storage of fats
increases, including cholesterol and fat-soluble
nutrients.



The amount of water in the body decreases, which
therefore decreases the absorption of water-soluble
nutrients. Also, there is less saliva and other lubricating fluids.



The liver and the kidneys cannot function as efficiently, thus affecting the elimination of wastes.



A decrease in the ease of digestion, with a decrease in
stomach acid production.



A loss of muscle strength and coordination, with an
accompanying loss of mobility, agility, and
flexibility.



A decline in sexual hormones and sexual functioning.



A decrease in the sensations of taste and smell.



Changes in the cardiovascular and respiratory systems, leading to decreased oxygen and nutrients
throughout the body.



Decreased functioning of the nervous system so that
nerve impulses are not transmitted as efficiently,
reflexes are not as sharp, and memory and learning
are diminished.



A decrease in bone strength and density.



Hormone levels, which gradually decline. The thyroid and sexual hormones are particularly affected.



Declining visual abilities. Age-related changes may
lead to diseases such as macular degeneration.



A compromised ability to produce vitamin D from
sunlight.



A reduction in protein formation leading to shrinkage in muscle mass and decreased bone formation,
possibly leading to osteoporosis.

David A. Cramer, MD

AFP test see Alpha-fetoprotein test
African American health see Minority health
African sleeping sickness see Sleeping
sickness
African trypanosomiasis see Sleeping
sickness
Agammaglobulinemia see Common variable
immunodeficiency
Aggression see Conduct disorder

I Aging
Definition
Starting at what is commonly called middle age,
operations of the human body begin to be more vulnerable to daily wear and tear; there is a general
decline in physical, and possibly mental, functioning.
In the Western countries, the length of life is often into
the 70s. The upward limit of the life span, however,
can be as high as 120 years. During the latter half of
life, an individual is more prone to have problems with
the various functions of the body and to develop any
number of chronic or fatal diseases. The cardiovascular, digestive, excretory, nervous, reproductive and
urinary systems are particularly affected. The most
common diseases of aging include Alzheimer’s, arthritis, cancer, diabetes, depression, and heart disease.

Description
Human beings reach a peak of growth and development around the time of their mid 20s. Aging is the
normal transition time after that flurry of activity.
Although there are quite a few age-related changes
that tax the body, disability is not necessarily a part
of aging. Health and lifestyle factors together with
the genetic makeup of the individual, and determines
the response to these changes. Body functions that are
most often affected by age include:
76

Causes and symptoms
There are several theories as to why the aging
body loses functioning. It may be that several factors
work together or that one particular factor is at work
more than others in a given individual.


Programmed senescence, or aging clock, theory. The
aging of the cells of each individual is programmed
into the genes, and there is a preset number of
GALE ENCYCLOPEDIA OF MEDICINE



Genetic theory. Human cells maintain their own seed
of destruction at the level of the chromosomes.



Connective tissue, or cross-linking theory. Changes
in the make-up of the connective tissue alter the
stability of body structures, causing a loss of elasticity and functioning, and leading to symptoms of
aging.





Free-radical theory. The most commonly held theory
of aging, it is based on the fact that ongoing chemical
reactions of the cells produce free radicals. In the
presence of oxygen, these free radicals cause the
cells of the body to break down. As time goes on,
more cells die or lose the ability to function, and the
body soon ceases to function as a whole.
Immunological theory. There are changes in the immune system as it begins to wear out, and the body is
more prone to infections and tissue damage, which
may finally cause death. Also, as the system breaks
down, the body is more apt to have autoimmune
reactions, in which the body’s own cells are mistaken
for foreign material and are destroyed or damaged
by the immune system.

Diagnosis
Many problems can arise due to age-related
changes in the body. Although there is no one test to
be given, a thorough physical exam and a basic blood
screening and blood chemistry panel can point to
areas in need of further attention. When older people
become ill, the first signs of disease are often nonspecific. Further exams should be conducted if any of the
following occur:

KEY TERMS
Antioxidants—Substances that reduce the damage
of the highly reactive free radicals that are the
byproducts of the cells.
Alzheimer’s disease—A condition causing a
decline in brain function that interferes with the
ability to reason and to perform daily activities.
Senescence—Aging.
Vata—One of the three main constitutional types
found under Ayurvedic principles. Keeping one’s
particular constitution in balance is considered
important in maintaining health.

take medications for various complaints. More
women than men use these medications. The most
common drugs used by the elderly are painkillers,
diuretics or water pills, sedatives, cardiac drugs, antibiotics, and mental health drugs.
Estrogen replacement therapy (ERT) is commonly prescribed to postmenopausal women for
symptoms of aging. It is often used in conjunction
with progesterone. ERT functions to help keep bones
strong, reduce risk of heart disease, restore vaginal
lubrication, and to improve skin elasticity. Evidence
suggests that it may also help maintain mental
functions.

Expected results
Aging is unavoidable, but major physical impairment is not. People can lead a healthy, disability-free
life well through their later years. A well established
support system of family, friends, and health care
providers, together with focus on good nutrition and
lifestyle habits and good stress management, can
prevent disease and lessen the impact of chronic
conditions.



diminished or lack of desire for food



increasing confusion



failure to thrive



urinary incontinence



dizziness

Alternative treatment



weight loss

Nutritional supplements



falling

Treatment
For the most part, doctors prescribe medications
to control the symptoms and diseases of aging. In the
United States, about two-thirds of people 65 and over
GALE ENCYCLOPEDIA OF MEDICINE

Aging

possible rejuvenations in the life of a given cell. When
cells die at a rate faster than they are replaced, organs
do not function properly, and they are soon unable
to maintain the functions necessary for life.

Consumption of a high–quality multivitamin is
recommended. Common nutritional deficiencies connected with aging include B vitamins, vitamins A and
C, folic acid, calcium, magnesium, zinc, iron, chromium, and trace minerals. Since stomach acids may
be decreased, it is suggested that the use of a powdered
multivitamin formula in gelatin capsules be used, as
77

Aging

this form is the easiest to digest. Such formulas may
also contain enzymes for further help with digestion.
Antioxidants can help to neutralize damage by
the free radical actions thought to contribute to problems of aging. They are also helpful in preventing
and treating cancer and in treating cataracts and
glaucoma. Supplements that serve as antioxidants
include:


Vitamin E, 400–1,000 IUs daily. Protects cell membranes against damage. It shows promise in prevention against heart disease, and Alzheimer’s and
Parkinson’s diseases.



Selenium, 50 mg taken twice daily. Research suggests
that selenium may play a role in reducing the risk of
cancer.



Beta-carotene, 25,000–40,000 IUs daily. May help in
treating cancer, colds and flu, arthritis, and immune
support.



Vitamin C, 1,000–2,000 mg per day. It may cause
diarrhea in large doses. If this occurs, however, all
that is needed is a decrease in the dosage.

Other supplements that are helpful in treating agerelated problems including:


B12/B-complex vitamins, studies show that B12 may
help reduce mental symptoms, such as confusion,
memory loss, and depression.



Coenzyme Q10 may be helpful in treating heart disease, as up to three-quarters cardiac patients have
been found to be lacking in this heart enzyme.
Hormones

The following hormone supplements may be
taken to prevent or to treat various age-related problems. However, caution should be taken before
beginning treatment, and the patient should consult
his or her health care professional.
DHEA improves brain functioning and serves as a
building block for many other important hormones in
the body. It may be helpful in restoring declining
hormone levels and in building up muscle mass,
strengthening the bones, and maintaining a healthy
heart.
Melatonin may be helpful for insomnia. It has also
been used to help fight viruses and bacterial infections,
reduce the risk of heart disease, improve sexual functioning, and to protect against cancer.
Human growth hormone (hGH) has been shown
to regulate blood sugar levels and to stimulate bone,
cartilage, and muscle growth while reducing fat.
78

Herbs
Garlic (Allium sativa) is helpful in preventing
heart disease, as well as improving the tone and texture
of skin. Garlic stimulates liver and digestive system
functions, and also helps in dealing with heart disease
and high blood pressure.
Siberian ginseng (Eleutherococcus senticosus)
supports the adrenal glands and immune functions.
It is believed to be helpful in treating problems related
to stress. Siberian ginseng also increases mental
and physical performance, and may be useful in treating memory loss, chronic fatigue, and immune
dysfunction.
Proanthocyanidins, or PCO, are Pycnogenol,
derived from grape seeds and skin, and from pine
tree bark, and may help in the prevention of cancer
and poor vision.
In Ayurvedic medicine, aging is described as a
process of increased vata, in which there is a tendency
to become thinner, drier, more nervous, more restless,
and more fearful, while having a loss of appetite
as well as sleep. Bananas, almonds, avocados, and
coconuts are some of the foods used in correcting
such conditions. One of the main herbs used for
such conditions is gotu kola (Centella asiatica),
which is used to revitalize the nervous system and
brain cells and to fortify the immune system. Gotu
kola is also used to treat memory loss, anxiety, and
insomnia.
In Chinese medicine, most symptoms of aging are
regarded as symptoms of a yin deficiency. Moistening
foods such as millet, barley soup, tofu, mung beans,
wheat germ, spirulina, potatoes, black sesame seeds,
walnuts, and flax seeds are recommended. Jing tonics
may also be used. These include deer antler, dodder
seeds, processed rehmannia, longevity soup, mussels,
and chicken.

Prevention
Preventive health practices such as healthy diet,
daily exercise, stress management, and control of lifestyle habits such as smoking and drinking, can
lengthen the life span and improve the quality of life
as people age. Exercise can improve the appetite, the
health of the bones, the emotional and mental outlook, and the digestion and circulation.
Drinking plenty of fluids aids in maintaining
healthy skin, good digestion, and proper elimination
of wastes. Up to eight glasses of water should be consumed daily, along with plenty of herbal teas, diluted
GALE ENCYCLOPEDIA OF MEDICINE

Because of a decrease in the sense of taste, older
people often increase their intake of salt, which can
contribute to high blood pressure and nutrient loss.
Use of sugar is also increased. Seaweeds and small
amounts of honey can be used as replacements.
Alcohol, nicotine, and caffeine all have potential
damaging effects, and should be limited or completely
eliminated from consumption.
A diet high in fiber and low in fat is recommended.
Processed foods should be replaced by complex carbohydrates, such as whole grains. If chewing becomes
a problem, there should be an increased intake of
protein drinks, freshly juiced fruits and vegetables,
and creamed cereals.
Resources
OTHER

‘‘Anti-Aging-Nutritional Program.’’ December 28, 2000.
<http:// www.healthy.net/hwlibrarybooks/haas/
perform/antiagin.htm>.
‘‘Effects of Hormone in the Body.’’ December 28, 2000.
<http://www.anti-aging.org/Effects_hGH.html>.
‘‘The Elderly-Nutritional Programs.’’ December 28, 2000.
<http://www.healthy.net/hwlibrarybooks/haas/
lifestage/elderly.htm>.
‘‘Evaluating the Elderly Patient: the Case for Assessment
Technology.’’ December 28, 2000. <http://text.nlm.
nih.gov/nih/ta/www/01.html>.
‘‘Herbal Phytotherapy and the Elderly.’’ December 28, 2000.
<http://www.healthy.net/hwlibrarybooks/hoffman/
elders/elders.htm>.
‘‘Pharmacokinetics.’’ Merck & Co., Inc. (1995-2000).
December 28, 2000. <http://www.merck.com/pubs/
mmanual/section22/chapter304/304a.htm>.
‘‘To a Long and Healthy Life.’’ December 28, 2000. <http://
www.healthy.net/hwlibraryarticles/aesoph/
longandhealthy.htm>.

Patience Paradox

I Agoraphobia
Definition
The word agoraphobia is derived from Greek
words literally meaning ‘‘fear of the marketplace.’’
The term is used to describe an irrational and often
disabling fear of being out in public.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Benzodiazepines—A group of tranquilizers often
used to treat anxiety.
Desensitization—A treatment for phobias which
involves exposing the phobic person to the feared
situation. It is often used in conjunction with
relaxation techniques.
Phobia—An intense and irrational fear of a specific
object, activity, or situation.

Description
Agoraphobia is just one type of phobia, or irrational fear. People with phobias feel dread or panic
when they face certain objects, situations, or activities.
People with agoraphobia frequently also experience
panic attacks, but panic attacks, or panic disorder,
are not a requirement for a diagnosis of agoraphobia.
The defining feature of agoraphobia is anxiety about
being in places from which escape might be embarrasing or difficult, or in which help might be unavailable.
The person suffering from agoraphobia usually avoids
the anxiety-provoking situation and may become
totally housebound.

Causes and symptoms
Agoraphobia is the most common type of phobia,
and it is estimated to affect between 5-12% of
Americans within their lifetime. Agoraphobia is
twice as common in women as in men and usually
strikes between the ages of 15-35.
The symptoms of the panic attacks which may
accompany agoraphobia vary from person to person,
and may include trembling, sweating, heart palpitations (a feeling of the heart pounding against the
chest), jitters, fatigue, tingling in the hands and feet,
nausea, a rapid pulse or breathing rate, and a sense of
impending doom.
Agoraphobia and other phobias are thought to be
the result of a number of physical and environmental
factors. For instance, they have been associated with
biochemical imbalances, especially related to certain neurotransmitters (chemical nerve messengers) in the brain.
People who have a panic attack in a given situation
(e.g., a shopping mall) may begin to associate the panic
with that situation and learn to avoid it. According to
some theories, irrational anxiety results from unresolved
emotional conflicts. All of these factors may play a
role to varying extents in different cases of agoraphobia.
79

Agoraphobia

fruit and vegetable juices, and fresh fruits and vegetables with high water content.

AIDS

Diagnosis
People who suffer from panic attacks should discuss the problem with a physician. The doctor can
diagnose the underlying panic or anxiety disorder
and make sure the symptoms aren’t related to some
other underlying medical condition.
The doctor makes the diagnosis of agoraphobia
based primarily on the patient’s description of his or
her symptoms. The person with agoraphobia experiences anxiety in situations where escape is difficult or
help is unavailable–or in certain situations, such as
being alone. While many people are somewhat apprehensive in these situations, the hallmark of agoraphobia is that a person’s active avoidance of the feared
situation impairs his or her ability to work, socialize,
or otherwise function.

Treatment
Treatment for agoraphobia usually consists of
both medication and psychotherapy. Usually,
patients can benefit from certain antidepressants,
such as amitriptyline (Elavil), or selective serotonin
reuptake inhibitors, such as paroxetine (Paxil),
fluoxetine (Prozac), or sertraline (Zoloft). In addition, patients may manage panic attacks in progress
with certain tranquilizers called benzodiazepines,
such as alprazolam (Xanax) or clonazepam
(Klonipin).
The mainstay of treatment for agoraphobia and
other phobias is cognitive behavioral therapy. A
specific technique that is often employed is called
desensitization. The patient is gradually exposed to
the situation that usually triggers fear and avoidance,
and, with the help of breathing or relaxation techniques, learns to cope with the situation. This helps
break the mental connection between the situation and
the fear, anxiety, or panic. Patients may also benefit
from psychodynamically oriented psychotherapy,
discussing underlying emotional conflicts with a therapist or support group.

Prognosis
With proper medication and psychotherapy, 90%
of patients will find significant improvement in their
symptoms.
Resources
PERIODICALS

Forsyth, Sondra. ‘‘I Panic When I’m Alone.’’Mademoiselle
April 1998: 119-24.
80

ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
Anxiety Disorders Association of America. 11900 Park
Lawn Drive, Ste. 100, Rockville, MD 20852. (800)
545-7367. <http://www.adaa.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Robert Scott Dinsmoor

Agranulocytosis see Neutropenia

I AIDS
Definition
Acquired immune deficiency syndrome (AIDS) is
an infectious disease caused by the human immunodeficiency virus (HIV). It was first recognized in the
United States in 1981. AIDS is the advanced form of
infection with the HIV virus, which may not cause
recognizable disease for a long period after the initial
exposure (latency). No vaccine is currently available to
prevent HIV infection. At present, all forms of AIDS
therapy are focused on improving the quality and
length of life for AIDS patients by slowing or halting
the replication of the virus and treating or preventing
infections and cancers that take advantage of a person’s weakened immune system.

Description
AIDS is considered one of the most devastating
public health problems in recent history. In June 2000,
the Centers for Disease Control and Prevention
(CDC) reported that 120,223 (includes only those
cases in areas that have confidential HIV reporting)
in the United States are HIV-positive, and 311,701 are
living with AIDS (includes only those cases where vital
status is known). Of these patients, 44% are gay or
bisexual men, 20% are heterosexual intravenous drug
users, and 17% are women. In addition, approximately 1,000-2,000 children are born each year with
HIV infection. The World Health Organization
(WHO) estimates that 33 million adults and 1.3 million children worldwide were living with HIV/AIDS as
of 1999 with 5.4 million being newly infected that year.
Most of these cases are in the developing countries of
Asia and Africa.
GALE ENCYCLOPEDIA OF MEDICINE

Risk virus
reaches entry
site

Risk virus
enters

Risk
inoculated

Moderate
Moderate
Low
Very low

Moderate
Moderate
Low
Very low

Very low
Low
Very low
Very low

Very high
Very low
Low

Very high
Very low
High

Very high
Very low
High

Low
High
High

Low
Low
High

Medium
Low
Very high

Blood:
Products
Shared needles
Accidental needle

High
High
Low

High
High
High

High
Very High
Low

Traumatic wound
Perinatal

Modest
High

High
High

High
High

Entry site
Conjuntiva
Oral mucosa
Nasal mucosa
Lower
respiratory
Anus
Skin, intact
Skin, broken
Sexual:
Vagina
Penis
Ulcers (STD)

Risk factors
AIDS can be transmitted in several ways. The risk
factors for HIV transmission vary according to category:






Sexual contact. Persons at greatest risk are those who
do not practice safe sex, those who are not monogamous, those who participate in anal intercourse, and
those who have sex with a partner with symptoms of
advanced HIV infection and/or other sexually transmitted diseases (STDs). In the United States and
Europe, most cases of sexually transmitted HIV infection have resulted from homosexual contact, whereas
in Africa, the disease is spread primarily through sexual
intercourse among heterosexuals.
Transmission in pregnancy. High-risk mothers
include women married to bisexual men or men
who have an abnormal blood condition called hemophilia and require blood transfusions, intravenous
drug users, and women living in neighborhoods
with a high rate of HIV infection among heterosexuals. The chances of transmitting the disease to the
child are higher in women in advanced stages of the
disease. Breast feeding increases the risk of transmission by 10-20%. The use of zidovudine (AZT) during
pregnancy, however, can decrease the risk of transmission to the baby.
Exposure to contaminated blood or blood products.
With the introduction of blood product screening in
the mid-1980s, the incidence of HIV transmission in
blood transfusions has dropped to one in every 100,000

GALE ENCYCLOPEDIA OF MEDICINE



Needle sticks among health care professionals.
Present studies indicate that the risk of HIV transmission by a needle stick is about one in 250. This
rate can be decreased if the injured worker is given
AZT, an anti-retroviral medication, in combination
with other medication.

HIV is not transmitted by handshakes or other
casual non-sexual contact, coughing or sneezing, or by
bloodsucking insects such as mosquitoes.
AIDS in women
AIDS in women is a serious public health concern.
Women exposed to HIV infection through heterosexual contact are the most rapidly growing risk
group in the United States population. The percentage
of AIDS cases diagnosed in women has risen from 7%
in 1985 to 23% in 1999. Women diagnosed with AIDS
may not live as long as men, although the reasons for
this finding are unclear.
AIDS in children
Since AIDS can be transmitted from an infected
mother to the child during pregnancy, during the birth
process, or through breast milk, all infants born to
HIV-positive mothers are a high-risk group. As of
2000, it was estimated that 87% of HIV-positive
women are of childbearing age; 41% of them are
drug abusers. Between 15-30% of children born to
HIV-positive women will be infected with the virus.
AIDS is one of the 10 leading causes of death in
children between one and four years of age. The interval between exposure to HIV and the development of
AIDS is shorter in children than in adults. Infants
infected with HIV have a 20-30% chance of developing AIDS within a year and dying before age three. In
the remainder, AIDS progresses more slowly; the
average child patient survives to seven years of age.
Some survive into early adolescence.

Causes and symptoms
Because HIV destroys immune system cells, AIDS
is a disease that can affect any of the body’s major
organ systems. HIV attacks the body through three
disease processes: immunodeficiency, autoimmunity,
and nervous system dysfunction.
81

AIDS

transfused. With respect to HIV transmission among
drug abusers, risk increases with the duration of using
injections, the frequency of needle sharing, the number of persons who share a needle, and the number of
AIDS cases in the local population.

Risk of acquiring HIV infection by entry site

AIDS
Mature HIV-1 viruses (above) and the lymphocyte from which they emerged (below). Two immature viruses can be seen budding
on the surface of the lymphocyte (right of center). (Photograph by Scott Camazir, Photo Researchers, Inc. Reproduced by
permission.)

Immunodeficiency describes the condition in
which the body’s immune response is damaged, weakened, or is not functioning properly. In AIDS, immunodeficiency results from the way that the virus binds
to a protein called CD4, which is primarily found on
the surface of certain subtypes of white blood cells
called helper T cells or CD4 cells. After the virus has
attached to the CD4 receptor, the virus-CD4 complex
refolds to uncover another receptor called a chemokine receptor that helps to mediate entry of the virus
into the cell. One chemokine receptor in particular,
CCR5, has gotten recent attention after studies
showed that defects in its structure (caused by genetic
mutations) cause the progression of AIDS to be prevented or slowed. Scientists hope that this discovery
will lead to the development of drugs that trigger an
artificial mutation of the CCR5 gene or target the
CCR5 receptor.

functioning of the remaining CD4 cells. Because the
immune system cells are destroyed, many different
types of infections and cancers that take advantage
of a person’s weakened immune system (opportunistic) can develop.

Once HIV has entered the cell, it can replicate
intracellularly and kill the cell in ways that are still
not completely understood. In addition to killing some
lymphocytes directly, the AIDS virus disrupts the

Researchers do not know precisely how HIV
attacks the nervous system since the virus can cause
damage without infecting nerve cells directly. One
theory is that, once infected with HIV, one type of

82

Autoimmunity is a condition in which the body’s
immune system produces antibodies that work against
its own cells. Antibodies are specific proteins produced in response to exposure to a specific, usually
foreign, protein or particle called an antigen. In this
case, the body produces antibodies that bind to blood
platelets that are necessary for proper blood clotting
and tissue repair. Once bound, the antibodies mark the
platelets for removal from the body, and they are
filtered out by the spleen. Some AIDS patients develop
a disorder, called immune-related thrombocytopenia
purpura (ITP), in which the number of blood platelets
drops to abnormally low levels.

GALE ENCYCLOPEDIA OF MEDICINE

AIDS

CENTRAL NERVOUS SYSTEM
LYMPHOPROLIFERATIVE DISEASE

MUCOCUTANEOUS

PNEUMONIA

SKIN
DIARRHEA

OPPORTUNISTIC INFECTIONS CAUSED BY AIDS
Because the immune system cells are destroyed by the AIDS virus, many different types of infections and cancers can develop,
taking advantage of a person’s weakened immune system. (Illustration by Electronic Illustrators Group.)

KEY TERMS
Acute retroviral syndrome—A group of symptoms
resembling mononucleosis that often are the first
sign of HIV infection in 50-70% of all patients and
45-90% of women.

Autoimmunity—A condition in which the body’s
immune system produces antibodies in response to
its own tissues or blood components instead of foreign particles or microorganisms.

AIDS dementia complex—A type of brain dysfunction caused by HIV infection that causes difficulty
thinking, confusion, and loss of muscular
coordination.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.

CCR5—A chemokine receptor; defects in its structure caused by genetic mutation cause the progression of AIDS to be prevented or slowed.
CD4—A type of protein molecule in human blood,
sometimes called the T4 antigen, that is present on
the surface of 65% of immune cells. The HIV virus
infects cells with CD4 surface proteins, and as a
result, depletes the number of T cells, B cells, natural
killer cells, and monocytes in the patient’s blood.

Antigen—Any substance that stimulates the body to
produce antibody.

GALE ENCYCLOPEDIA OF MEDICINE

83

AIDS

Most of the damage to an AIDS patient’s immune
system is done by the virus’ destruction of CD4+
lymphocytes.
Chemokine receptor—A receptor on the surface of
some types of immune cells that helps to mediate
entry of HIV into the cell.
Hairy leukoplakia of the tongue—A white area of
diseased tissue on the tongue that may be flat or
slightly raised. It is caused by the Epstein-Barr virus
and is an important diagnostic sign of AIDS.
Hemophilia—Any of several hereditary blood coagulation disorders occurring almost exclusively in
males. Because blood does not clot properly, even
minor injuries can cause significant blood loss that
may require a blood transfusion, with its associated
minor risk of infection.
Human immunodeficiency virus (HIV)—A transmissible retrovirus that causes AIDS in humans. Two
forms of HIV are now recognized: HIV-1, which
causes most cases of AIDS in Europe, North and
South America, and most parts of Africa; and HIV-2,
which is chiefly found in West African patients.
HIV-2, discovered in 1986, appears to be less virulent
than HIV-1 and may also have a longer latency period.
Immunodeficient—A condition in which the body’s
immune response is damaged, weakened, or is not
functioning properly.
Kaposi’s sarcoma—A cancer of the connective tissue
that produces painless purplish red (in people with
light skin) or brown (in people with dark skin) blotches
on the skin. It is a major diagnostic marker of AIDS.
Latent period—Also called incubation period, the
time between infection with a disease-causing
agent and the development of disease.
Lymphocyte—A type of white blood cell that is important in the formation of antibodies and that can be used
to monitor the health of AIDS patients.
Lymphoma—A cancerous tumor in the lymphatic
system that is associated with a poor prognosis in
AIDS patients.
Macrophage—A large white blood cell, found primarily in the bloodstream and connective tissue, that
helps the body fight off infections by ingesting the
disease-causing organism. HIV can infect and kill
macrophages.
Monocyte—A large white blood cell that is formed
in the bone marrow and spleen. About 4% of the
white blood cells in normal adults are monocytes.

84

Mycobacterium avium (MAC) infection—A type
of opportunistic infection that occurs in about 40%
of AIDS patients and is regarded as an AIDS-defining
disease.
Non-nucleoside reverse transcriptase inhibitors—
The newest class of antiretroviral drugs that work
by inhibiting the reverse transcriptase enzyme
necessary for HIV replication.
Nucleoside analogues—The first group of effective
anti-retroviral medications. They work by interfering
with the AIDS virus’ synthesis of DNA.
Opportunistic infection—An infection by organisms
that usually don’t cause infection in people whose
immune systems are working normally.
Persistent generalized lymphadenopathy (PGL)—A
condition in which HIV continues to produce
chronic painless swellings in the lymph nodes during
the latency period.
Pneumocystis carinii pneumonia (PCP)—An
opportunistic infection caused by a fungus that is a
major cause of death in patients with late-stage
AIDS.
Progressive
multifocal
leukoencephalopathy
(PML)—A disease caused by a virus that destroys
white matter in localized areas of the brain. It is
regarded as an AIDS-defining illness.
Protease inhibitors—The second major category of
drug used to treat AIDS that works by suppressing the
replication of the HIV virus.
Protozoan—A single-celled, usually microscopic
organism that is eukaryotic and, therefore, different
from bacteria (prokaryotic).
Retrovirus—A virus that contains a unique enzyme
called reverse transcriptase that allows it to replicate
within new host cells.
T cells—Lymphocytes that originate in the thymus
gland. T cells regulate the immune system’s response
to infections, including HIV. CD4 lymphocytes are a
subset of T lymphocytes.
Thrush—A yeast infection of the mouth characterized by white patches on the inside of the mouth and
cheeks.
Viremia—The measurable presence of virus in the
bloodstream that is a characteristic of acute retroviral
syndrome.
Wasting syndrome—A progressive loss of weight
and muscle tissue caused by the AIDS virus.

GALE ENCYCLOPEDIA OF MEDICINE

The course of AIDS generally progresses through
three stages, although not all patients will follow this
progression precisely:
Acute retroviral syndrome
Acute retroviral syndrome is a term used to
describe a group of symptoms that can resemble
mononucleosis and that may be the first sign of HIV
infection in 50-70% of all patients and 45-90% of
women. Most patients are not recognized as infected
during this phase and may not seek medical attention.
The symptoms may include fever, fatigue, muscle
aches, loss of appetite, digestive disturbances, weight
loss, skin rashes, headache, and chronically swollen
lymph nodes (lymphadenopathy). Approximately 2533% of patients will experience a form of meningitis
during this phase in which the membranes that cover
the brain and spinal cord become inflamed. Acute
retroviral syndrome develops between one and six
weeks after infection and lasts for two to three
weeks. Blood tests during this period will indicate the
presence of virus (viremia) and the appearance of the
viral p24 antigen in the blood.

or ulcers, or other infections of the mouth; diarrhea
and other gastrointestinal symptoms that cause malnutrition and weight loss; diseases of the lungs and
kidneys; and degeneration of the nerve fibers in the
arms and legs. HIV infection of the nervous system
leads to general loss of strength, loss of reflexes, and
feelings of numbness or burning sensations in the feet
or lower legs.
Late-stage disease (AIDS)
AIDS is usually marked by a very low number of
CD4+ lymphocytes, followed by a rise in the frequency of opportunistic infections and cancers.
Doctors monitor the number and proportion of
CD4+ lymphocytes in the patient’s blood in order to
assess the progression of the disease and the effectiveness of different medications. About 10% of infected
individuals never progress to this overt stage of the
disease and are referred to as nonprogressors.
OPPORTUNISTIC INFECTIONS. Once the patient’s
CD4+ lymphocyte count falls below 200 cells/mm 3,
he or she is at risk for a variety of opportunistic infections. The infectious organisms may include the
following:


Fungi. The most common fungal disease associated
with AIDS is Pneumocystis carinii pneumonia (PCP).
PCP is the immediate cause of death in 15-20% of
AIDS patients. It is an important measure of a
patient’s prognosis. Other fungal infections include
a yeast infection of the mouth (candidiasis or thrush)
and cryptococcal meningitis.



Protozoa. Toxoplasmosis is a common opportunistic
infection in AIDS patients that is caused by a protozoan. Other diseases in this category include isoporiasis and cryptosporidiosis.



Mycobacteria. AIDS patients may develop tuberculosis or MAC infections. MAC infections are caused
by Mycobacterium avium-intracellulare, and occur in
about 40% of AIDS patients. It is rare until CD4+
counts falls below 50 cells/mm3.



Bacteria. AIDS patients are likely to develop bacterial infections of the skin and digestive tract.



Viruses. AIDS patients are highly vulnerable to cytomegalovirus (CMV), herpes simplex virus (HSV),
varicella zoster virus (VZV), and Epstein-Barr virus
(EBV) infections. Another virus, JC virus, causes
progressive destruction of brain tissue in the brain
stem, cerebrum, and cerebellum (multifocal leukoencephalopathy or PML), which is regarded as an
AIDS-defining illness by the Centers for Disease
Control and Prevention.

Latency period
After the HIV virus enters a patient’s lymph nodes
during the acute retroviral syndrome stage, the disease
becomes latent for as many as 10 years or more before
symptoms of advanced disease develop. During
latency, the virus continues to replicate in the lymph
nodes, where it may cause one or more of the following
conditions:
PERSISTENT GENERALIZED LYMPHADENOPATHY
(PGL). Persistent generalized lymphadenopathy, or

PGL, is a condition in which HIV continues to produce chronic painless swellings in the lymph nodes
during the latency period. The lymph nodes that are
most frequently affected by PGL are those in the areas
of the neck, jaw, groin, and armpits. PGL affects
between 50-70% of patients during latency.
CONSTITUTIONAL SYMPTOMS. Many patients will
develop low-grade fevers, chronic fatigue, and general
weakness. HIV may also cause a combination of food
malabsorption, loss of appetite, and increased metabolism that contribute to the so-called AIDS wasting
or wasting syndrome.
OTHER ORGAN SYSTEMS. At any time during the
course of HIV infection, patients may suffer from a
yeast infection in the mouth called thrush, open sores

GALE ENCYCLOPEDIA OF MEDICINE

85

AIDS

immune system cell, called a macrophage, begins to
release a toxin that harms the nervous system.

AIDS

AIDS DEMENTIA COMPLEX AND NEUROLOGIC
COMPLICATIONS. AIDS dementia complex is usually

a late complication of the disease. It is unclear whether
it is caused by the direct effects of the virus on the
brain or by intermediate causes. AIDS dementia complex is marked by loss of reasoning ability, loss of
memory, inability to concentrate, apathy and loss of
initiative, and unsteadiness or weakness in walking.
Some patients also develop seizures. There are no
specific treatments for AIDS dementia complex.
MUSCULOSKELETAL COMPLICATIONS. Patients in
late-stage AIDS may develop inflammations of the
muscles, particularly in the hip area, and may have
arthritis-like pains in the joints.
ORAL SYMPTOMS. In addition to thrush and painful ulcers in the mouth, patients may develop a condition called hairy leukoplakia of the tongue. This
condition is also regarded by the CDC as an indicator
of AIDS. Hairy leukoplakia is a white area of diseased
tissue on the tongue that may be flat or slightly raised.
It is caused by the Epstein-Barr virus.
AIDS-RELATED CANCERS. Patients with late-stage

AIDS may develop Kaposi’s sarcoma (KS), a skin
tumor that primarily affects homosexual men. KS is
the most common AIDS-related malignancy. It is
characterized by reddish-purple blotches or patches
(brownish in African-Americans) on the skin or in
the mouth. About 40% of patients with KS develop
symptoms in the digestive tract or lungs. KS may be
caused by a herpes virus-like sexually transmitted disease agent rather than HIV.
The second most common form of cancer in AIDS
patients is a tumor of the lymphatic system (lymphoma). AIDS-related lymphomas often affect the
central nervous system and develop very aggressively.
Invasive cancer of the cervix (related to certain
types of human papilloma virus [HPV]) is an important diagnostic marker of AIDS in women.
While incidence of AIDS-defining cancers such as
Kaposi’s sarcoma and cervical cancer have decreased
since increase use of antiretroviral therapy, other cancers has increased in AIDS patients. People with HIV
has shown higher incidence of lung cancer, head and
neck cancers, Hodgkin’s lymphoma, melanoma, and
anorectal cancer from 1992 to 2002.

Diagnosis
Because HIV infection produces such a wide
range of symptoms, the CDC has drawn up a list
of 34 conditions regarded as defining AIDS. The
86

physician will use the CDC list to decide whether the
patient falls into one of these three groups:


definitive diagnoses with or without laboratory evidence of HIV infection



definitive diagnoses with laboratory evidence of HIV
infection



presumptive diagnoses with laboratory evidence of
HIV infection.
Physical findings

Almost all the symptoms of AIDS can occur with
other diseases. The general physical examination may
range from normal findings to symptoms that are
closely associated with AIDS. These symptoms are
hairy leukoplakia of the tongue and Kaposi’s sarcoma. When the doctor examines the patient, he or
she will look for the overall pattern of symptoms
rather than any one finding.
Laboratory tests for HIV infection
BLOOD TESTS (SEROLOGY). The first blood test
for AIDS was developed in 1985. At present, patients
who are being tested for HIV infection are usually
given an enzyme-linked immunosorbent assay
(ELISA) test for the presence of HIV antibody in
their blood. Positive ELISA results are then tested
with a Western blot or immunofluorescence (IFA)
assay for confirmation. The combination of the
ELISA and Western blot tests is more than 99.9%
accurate in detecting HIV infection within four to
eight weeks following exposure. The polymerase
chain reaction (PCR) test can be used to detect the
presence of viral nucleic acids in the very small number
of HIV patients who have false-negative results on the
ELISA and Western blot tests. These tests are also
used to detect viruses and bacterium other than HIV
and AIDS.
OTHER LABORATORY TESTS. In addition to diagnostic blood tests, there are other blood tests that are
used to track the course of AIDS in patients that have
already been diagnosed. These include blood counts,
viral load tests, p24 antigen assays, and measurements
of 2-microglobulin ( 2M).

Doctors will use a wide variety of tests to diagnose
the presence of opportunistic infections, cancers, or
other disease conditions in AIDS patients. Tissue
biopsies, samples of cerebrospinal fluid, and sophisticated imaging techniques, such as magnetic resonance
imaging (MRI) and computed tomography scans (CT)
are used to diagnose AIDS-related cancers, some
opportunistic infections, damage to the central
GALE ENCYCLOPEDIA OF MEDICINE

zalcitabine (ddC), stavudine (d4T), lamivudine
(3TC), and abacavir (ABC).


Protease inhibitors. Protease inhibitors can be effective against HIV strains that have developed resistance to nucleoside analogues, and are often used in
combination with them. These compounds include
saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, and lopinavir..



Non-nucleoside reverse transcriptase inhibitors. This
is a new class of antiretroviral agents. Three are
available, nevirapine, which was approved first, delavirdine and efavirin.



Fusion inhibitors, the newest class of antiretrovirals.
They block specific proteins on the surface of the
virus or the CD4 cell. These proteins help the virus
gain entry into the cell.The only FDA approved
fusion inhibitor as of spring 2004 was enfuvirtide.

Diagnosis in children
Diagnostic blood testing in children older than 18
months is similar to adult testing, with ELISA screening confirmed by Western blot. Younger infants can
be diagnosed by direct culture of the HIV virus, PCR
testing, and p24 antigen testing.
In terms of symptoms, children are less likely than
adults to have an early acute syndrome. They are,
however, likely to have delayed growth, a history of
frequent illness, recurrent ear infections, a low blood
cell count, failure to gain weight, and unexplained
fevers. Children with AIDS are more likely to develop
bacterial infections, inflammation of the lungs, and
AIDS-related brain disorders than are HIV-positive
adults.

Treatment
Treatment for AIDS covers four considerations:
TREATMENT OF OPPORTUNISTIC INFECTIONS AND
MALIGNANCIES. Most AIDS patients require complex

long-term treatment with medications for infectious
diseases. This treatment is often complicated by the
development of resistance in the disease organisms.
AIDS-related malignancies in the central nervous system are usually treated with radiation therapy.
Cancers elsewhere in the body are treated with
chemotherapy.
PROPHYLACTIC TREATMENT FOR OPPORTUNISTIC
INFECTIONS. Prophylactic treatment is treatment that

is given to prevent disease. AIDS patients with a history of Pneumocystis pneumonia; with CD4+ counts
below 200 cells/mm3 or 14% of lymphocytes; weight
loss; or thrush should be given prophylactic medications. The three drugs given are trimethoprimsulfamethoxazole, dapsone, or pentamidine in aerosol
form.
ANTI-RETROVIRAL TREATMENT. In

recent years
researchers have developed drugs that suppress HIV
replication, as distinct from treating its effects on the
body. These drugs fall into four classes:


Nucleotide analogues. These drugs work by interfering with the action of HIV reverse transcriptase
inside infected cells, thus ending the virus’ replication
process. These drugs include zidovudine (sometimes
called azidothymidine or AZT), didanosine (ddI),

GALE ENCYCLOPEDIA OF MEDICINE

Treatment guidelines for these agents are in constant change as new medications are developed and
introduced. Two principles currently guide doctors in
working out drug regimens for AIDS patients: using
combinations of drugs rather than one medication
alone; and basing treatment decisions on the results
of the patient’s viral load tests.
STIMULATION OF BLOOD CELL PRODUCTION.

Because many patients with AIDS suffer from abnormally low levels of both red and white blood cells,
they may be given medications to stimulate blood cell
production. Epoetin alfa (erythropoietin) may be
given to anemic patients. Patients with low white
blood cell counts may be given filgrastim or
sargramostim.
Treatment in women
Treatment of pregnant women with HIV is particularly important in that anti-retroviral therapy
has been shown to reduce transmission to the infant
by 65%.

Alternative treatment
Alternative treatments for AIDS can be grouped
into two categories: those intended to help the immune
system and those aimed at pain control. Treatments
that may enhance the function of the immune system
include Chinese herbal medicine and western herbal
medicine, macrobiotic and other special diets, guided
imagery and creative visualization, homeopathy, and
vitamin therapy. Pain control therapies include hydrotherapy, reiki, acupuncture, meditation, chiropractic
treatments, and therapeutic massage. Alternative
87

AIDS

nervous system, and wasting of the muscles. Urine and
stool samples are used to diagnose infections caused
by parasites. AIDS patients are also given blood tests
for syphilis and other sexually transmitted diseases.

AIDS tests

therapies can also be used to help with side effects of
the medications used in the treatment of AIDS.

Prognosis
At the present time, there is no cure for AIDS.
Treatment stresses aggressive combination drug
therapy for those patients with access to the expensive medications and who tolerate them adequately.
The use of these multi-drug therapies has significantly reduced the numbers of deaths, in this country,
resulting from AIDS. The data is still inconclusive,
but the potential exists to possibly prolong life
indefinitely using these and other drug therapies to
boost the immune system, keep the virus from replicating, and ward off opportunistic infections and
malignancies.
Prognosis after the latency period depends on the
patient’s specific symptoms and the organ systems
affected by the disease. Patients with AIDS-related
lymphomas of the central nervous system die within
two to three months of diagnosis; those with systemic
lymphomas may survive for eight to ten months.



If someone suspects HIV infection, he or she
should be tested for HIV. If treated aggressively
and early, the development of AIDS may be postponed indefinitely. If HIV infection is confirmed, it
is also vital to let sexual partners know so that they
can be tested and, if necessary, receive medical
attention.

Resources
PERIODICALS

Boschert, Sherry. ‘‘Some Ca Increasing in Post-HAART
Era.’’ Clinical Psychiatry News June 2004: 75.
Godwin, Catherine. ‘‘WhatÆs New in the Fight Against
AIDS.’’ RN April 2004: 46–54.
ORGANIZATIONS

Gay Men’s Health Crisis, Inc., 129 West 20th Street, New
York, NY 10011-0022. (212) 807-6655.
National AIDS Hot Line. (800) 342-AIDS (English). (800)
344-SIDA (Spanish). (800) AIDS-TTY (hearingimpaired).
OTHER

‘‘FDA Approved Drugs for HIV Infection and AIDSRelatedConditions.’’ HIV/AIDS Treatment Information
Service website. January 2001.<http://hivatis.org>.

Rebecca J. Frey, PhD
Teresa G. Odle

Prevention
As of 2005, there was no vaccine effective against
AIDS. Several vaccines are currently being investigated, however, both to prevent initial HIV infection
and as a therapeutic treatment to prevent HIV from
progressing to full-blown AIDS.
In the meantime, there are many things that can
be done to prevent the spread of AIDS:


Being monogamous and practice safe sex.
Individuals must be instructed in the proper use of
condoms and urged to practice safe sex. Besides
avoiding the risk of HIV infection, condoms are
successful in preventing other sexually transmitted
diseases and unwanted pregnancies. Before engaging
in a sexual relationship with someone, getting tested
for HIV infection is recommended.



Avoiding needle sharing among intravenous drug
users.



Although blood and blood products are carefully
monitored, those individuals who are planning to
undergo major surgery may wish to donate blood
ahead of time to prevent a risk of infection from a
blood transfusion.



Healthcare professionals must take all necessary precautions by wearing gloves and masks when handling body fluids and preventing needle-stick injuries.

88

AIDS serology see AIDS tests

I AIDS tests
Definition
AIDS tests, short for acquired immunodeficiency
syndrome tests, cover a number of different procedures used in the diagnosis and treatment of HIV
patients. These tests sometimes are called AIDS
serology tests. Serology is the branch of immunology
that deals with the contents and characteristics of
blood serum. Serum is the clear light yellow part
of blood that remains liquid when blood cells form
a clot. AIDS serology evaluates the presence of
human immunodeficiency virus (HIV) infection in
blood serum and its effects on each patient’s immune
system.

Purpose
AIDS serology serves several different purposes.
Some AIDS tests are used to diagnose patients or
GALE ENCYCLOPEDIA OF MEDICINE

AIDS tests

confirm a diagnosis; others are used to measure the
progression of the disease or the effectiveness of specific treatment regimens. Some AIDS tests also can be
used to screen blood donations for safe use in
transfusions.
In order to understand the different purposes
of the blood tests used with AIDS patients, it is helpful to understand how HIV infection affects human
blood and the immune system. HIV is a retrovirus that
enters the blood stream of a new host in the following
ways:


by sexual contact



by contact with infected body fluids (such as blood
and urine)



by transmission during pregnancy, or



through transfusion of infected blood products

A retrovirus is a virus that contains a unique
enzyme called reverse transcriptase that allows it to
replicate within new host cells. The virus binds to a
protein called CD4, which is found on the surface of
certain subtypes of white blood cells, including helper
T cells, macrophages, and monocytes. Once HIV
enters the cell, it can replicate and kill the cell in
ways that are still not completely understood. In addition to killing some lymphocytes directly, the AIDS
virus disrupts the functioning of the remaining CD4
cells. CD4 cells ordinarily produce a substance called
interleukin-2 (IL-2), which stimulates other cells
(T cells and B cells) in the human immune system
to respond to infections. Without the IL-2, T cells do
not reproduce as they normally would in response to the
HIV virus, and B cells are not stimulated to respond
to the infection.

Precautions
In some states such as New York, a signed consent
form is needed in order to administer an AIDS test. As
with all blood tests, healthcare professionals should
always wear latex gloves and avoid being pricked by
the needle used in drawing blood for the tests. It may
be difficult to get blood from a habitual intravenous
drug user due to collapsed veins.

Description
Diagnostic tests
Diagnostic blood tests for AIDS usually are given
to persons in high-risk populations who may have
been exposed to HIV or who have the early symptoms
of AIDS. Most persons infected with HIV will develop
GALE ENCYCLOPEDIA OF MEDICINE

A three-dimensional model of the HIV virus. (Corbis
Corporation (New York). Reproduced by permission.)

a detectable level of antibody within three months of
infection. The condition of testing positive for HIV
antibody in the blood is called seroconversion, and
persons who have become HIV-positive are called
seroconverters.
It is possible to diagnose HIV infection by isolating the virus itself from a blood sample or by demonstrating the presence of HIV antigen in the blood.
Viral culture, however, is expensive, not widely available, and slow—it takes 28 days to complete the viral
culture test. More common are blood tests that work
by detecting the presence of antibodies to the HIV
virus. These tests are inexpensive, widely available,
and accurate in detecting 99.9% of AIDS infections
when used in combination to screen patients and
confirm diagnoses.
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA).

This type of blood test is used to screen blood for
transfusions as well as diagnose patients. An ELISA
test for HIV works by attaching HIV antigens to a
plastic well or beads. A sample of the patient’s blood
serum is added, and excess proteins are removed.
A second antibody coupled to an enzyme is added,
followed by addition of a substance that will cause
the enzyme to react by forming a color. An instrument called a spectrophotometer can measure the
color. The name of the test is derived from the use
of the enzyme that is coupled or linked to the second
antibody.
89

AIDS tests

KEY TERMS
Antibody—A protein in the blood that identifies and
helps remove disease organisms or their toxins.
Antibodies are secreted by B cells. AIDS diagnostic
tests work by demonstrating the presence of HIV
antibody in the patient’s blood.

South America, and most parts of Africa; and
HIV-2, which is chiefly found in West African
patients. HIV-2, discovered in 1986, appears to be
less virulent than HIV-1, but also may have a longer
latency period.

Antigen—Any substance that stimulates the body to
produce antibodies.
B cell—A type of white blood cell derived from bone
marrow. B cells are sometimes called B lymphocytes. They secrete antibody and have a number of
other complex functions within the human immune
system.

Immunofluorescent assay (IFA)—A blood test sometimes used to confirm ELISA results instead of using
the Western blotting. In an IFA test, HIV antigen is
mixed with a fluorescent compound and then with a
sample of the patient’s blood. If HIV antibody is
present, the mixture will fluoresce when examined
under ultraviolet light.
Lymphocyte—A type of white blood cell that is
important in the formation of antibodies. Doctors
can monitor the health of AIDS patients by measuring the number or proportion of certain types of
lymphocytes in the patient’s blood.
Macrophage—A large white blood cell, found primarily in the bloodstream and connective tissue, that
helps the body fight off infections by ingesting the
disease organism. HIV can infect and kill
macrophages.

CD4—A type of protein molecule in human blood
that is present on the surface of 65% of human
T cells. CD4 is a receptor for the HIV virus. When
the HIV virus infects cells with CD4 surface proteins, it
depletes the number of T cells, B cells, natural killer
cells, and monocytes in the patient’s blood. Most of
the damage to an AIDS patient’s immune system is
done by the virus’ destruction of CD4+ lymphocytes.
CD4 is sometimes called the T4 antigen.
Complete blood count (CBC)—A routine analysis
performed on a sample of blood taken from the
patient’s vein with a needle and vacuum tube. The
measurements taken in a CBC include a white blood
cell count, a red blood cell count, the red cell distribution width, the hematocrit (ratio of the volume
of the red blood cells to the blood volume), and the
amount of hemoglobin (the blood protein that carries
oxygen). CBCs are a routine blood test used for many
medical reasons, not only for AIDS patients. They
can help the doctor determine if a patient is in
advanced stages of the disease.
Electrophoresis—A method of separating complex
protein molecules suspended in a gel by running an
electric current through the gel.
Enzyme-linked immunosorbent assay (ELISA)—A
diagnostic blood test used to screen patients for
AIDS or other viruses. The patient’s blood is mixed
with antigen attached to a plastic tube or bead surface. A sample of the patient’s blood serum is added,
and excess proteins are removed. A second antibody
coupled to an enzyme is added, followed by a chemical that will cause a color reaction that can be
measured by a special instrument.
Human immunodeficiency virus (HIV)—A transmissible retrovirus that causes AIDS in humans. Two
forms of HIV are now recognized: HIV-1, which
causes most cases of AIDS in Europe, North and

90

Monocyte—A large white blood cell that is formed
in the bone marrow and spleen. About 4% of the
white blood cells in normal adults are monocytes.
Opportunistic infection—An infection that develops
only when a person’s immune system is weakened,
as happens to AIDS patients.
Polymerase chain reaction (PCR)—A test performed
to evaluate false-negative results to the ELISA and
Western blot tests. In PCR testing, numerous copies
of a gene are made by separating the two strands of
DNA containing the gene segment, marking its location, using DNA polymerase to make a copy, and
then continuously replicating the copies. The amplification of gene sequences that are associated with
HIV allows for detection of the virus by this method.
Retrovirus—A virus that contains a unique enzyme
called reverse transcriptase that allows it to replicate
within new host cells.
Seroconversion—The change from HIV- negative to
HIV-positive status during blood testing. Persons
who are HIV-positive are called seroconverters.
Serology—The analysis of the contents and properties of blood serum.
Serum—The part of human blood that remains liquid
when blood cells form a clot. Human blood serum is
clear light yellow in color.

GALE ENCYCLOPEDIA OF MEDICINE

Viral load test—A new blood test for monitoring the
speed of HIV replication in AIDS patients. The viral
load test is based on PCR techniques and supplements the CD4+ cell count tests.
Western blot—A technique developed in 1979 that
is used to confirm ELISA results. HIV antigen is purified by electrophoresis and attached by blotting to a
nylon or nitrocellulose filter. The patient’s serum is

The latest generation of ELISA tests are 99.5%
sensitive to HIV. Occasionally, the ELISA test will be
positive for a patient without symptoms of AIDS from
a low-risk group. Because this result is likely to be a
false-positive, the ELISA must be repeated on the same
sample of the patient’s blood. If the second ELISA is
positive, the result should be confirmed by the
Western blot test.
WESTERN BLOT (IMMUNOBLOT). The Western blot
or immunoblot test is used as a reference procedure to
confirm the diagnosis of AIDS. In Western blot testing, HIV antigen is purified by electrophoresis (large
protein molecules are suspended in a gel and separated
from one another by running an electric current
through the gel). The HIV antigens are attached by
blotting to a nylon or nitrocellulose filter. The
patient’s serum is reacted against the filter, followed
by treatment with developing chemicals that allow
HIV antibody to show up as a colored patch or blot.
A commercially produced Western blot test for HIV-1
is now available. It consists of a prefabricated
strip that is incubated with a sample of the patient’s
blood serum and the developing chemicals. About
nine different HIV-1 proteins can be detected in
the blots.

When used in combination with ELISA testing,
Western blot testing is 99.9% specific. It can, however,
yield false negatives in patients with very early HIV
infection and in those infected by HIV-2. In some
patients the Western blot yields indeterminate results.
IMMUNOFLUORESCENCE ASSAY (IFA). This method
is sometimes used to confirm ELISA results instead of
Western blotting. An IFA test detects the presence of
HIV antibody in a sample of the patient’s serum by
mixing HIV antigen with a fluorescent chemical, adding the blood sample, and observing the reaction
under a microscope with ultraviolet light.

GALE ENCYCLOPEDIA OF MEDICINE

reacted against the filter, followed by treatment with
developing chemicals that allow HIV antibody to
show up as a colored patch or blot. If the patient is
HIV-positive, there will be stripes at specific locations for two or more viral proteins. A negative result
is blank.
WBC differential—A white blood cell count in
which the technician classifies the different white
blood cells by type as well as calculating the
number of each type. A WBC differential is necessary to calculate the absolute CD4+ lymphocyte
count.

POLYMERASE CHAIN REACTION (PCR). This test is
used to evaluate the very small number of AIDS
patients with false-negative ELISA and Western blot
tests. These patients are sometimes called antibodynegative asymptomatic (without symptoms) carriers,
because they do not have any symptoms of AIDS and
there is no detectable quantity of antibody in the blood
serum. Antibody-negative asymptomatic carriers may
be responsible for the very low ongoing risk of HIV
infection transmitted by blood transfusions. It is estimated that the risk is between 1 in 10,000 and 1 in
100,000 units of transfused blood.

The polymerase chain reaction (PCR) test can
measure the presence of viral nucleic acids in the
patient’s blood even when there is no detectable antibody to HIV. This test works by amplifying the presence of HIV nucleic acids in a blood sample.
Numerous copies of a gene are made by separating
the two strands of DNA containing the gene segment,
marking its location, using DNA polymerase to make
a copy, and then continuously replicating the copies. It
is questionable whether PCR will replace Western
blotting as the method of confirming AIDS diagnoses.
Although PCR can detect the low number of persons
(1%) with HIV infections that have not yet generated
an antibody response to the virus, the overwhelming
majority of infected persons will be detected by ELISA
screening within one to three months of infection.
In addition, PCR testing is based on present knowledge of the genetic sequences in HIV. Since the virus
is continually generating new variants, PCR testing
could yield a false negative in patients with these
new variants. In 2004, researchers reported on a new
test that was more sensitive to HIV, detecting the
infection in as little as 12 days after infection.
However, the manufacturer was still seeking FDA
approval for the test, which would cost about the
same as PCR testing.
91

AIDS tests

T cells—Lymphocytes that originate in the thymus
gland. T cells regulate the immune system’s response
to infections, including HIV. CD4 lymphocytes are a
subset of T lymphocytes.

AIDS tests

In 1999, the U.S. Food and Drug Administration
(FDA) approved an HIV home testing kit. The kit
contained multiple components, including material
for specimen collection, a mailing envelope to send
the specimen to a laboratory for analysis, and provides
pre- and post-test counseling. It uses a finger prick
process for blood collection. Other tests have been in
development that would allow patients to monitor
their own therapy in the home without sending out
for results.

the patient’s white blood cell count (WBC) by the
percentage of lymphocytes among the white blood
cells, and multiplying the result by the percentage
of lymphocytes bearing the CD4+ marker. An absolute count below 200-300 CD+4 lymphocytes
in 1 cubic millimeter (mm3) of blood indicates that
the patient is vulnerable to some opportunistic
infections.


Prognostic tests
Blood tests to evaluate patients already diagnosed
with HIV infection are as important as the diagnostic
tests. Because AIDS has a long latency period, some
persons may be infected with the virus for 10 years or
longer before they develop symptoms of AIDS. These
patients are sometimes called antibody-positive
asymptomatic carriers. Prognostic tests also help
drug researchers evaluate the usefulness of new medications in treating AIDS.
BLOOD CELL COUNTS. Doctors can measure the
number or proportion of certain types of cells in an
AIDS patient’s blood to see whether and how rapidly
the disease is progressing, or whether certain treatments are helping the patient. These cell count tests
include:




Complete blood count (CBC). A CBC is a routine
analysis performed on a sample of blood taken
from the patient’s vein with a needle and vacuum
tube. The measurements taken in a CBC include a
white blood cell count (WBC), a red blood cell count
(RBC), the red cell distribution width, the hematocrit
(ratio of the volume of the red blood cells to the
blood volume), and the amount of hemoglobin (the
blood protein that carries oxygen). Although CBCs
are used on more than just AIDS patients, they can
help the doctor determine if an AIDS patient has an
advanced form of the disease. Specific AIDS-related
signs in a CBC include a low hematocrit, a sharp
decrease in the number of blood platelets, and a
low level of a certain type of white blood cell called
neutrophils.
Absolute CD4+ lymphocytes. A lymphocyte is a
type of white blood cell that is important in the
formation of an immune response. Because HIV
targets CD4+ lymphocytes, their number in the
patient’s blood can be used to track the course of
the infection. This blood cell count is considered the
most accurate indicator for the presence of an opportunistic infection in an AIDS patient. The absolute
CD4+ lymphocyte count is obtained by multiplying

92

CD4+ lymphocyte percentage. Some doctors think
that this is a more accurate test than the absolute
count because the percentage does not depend on a
manual calculation of the number of types of different white blood cells. A white blood cell count that is
broken down into categories in this way is called a
WBC differential.

It is important for doctors treating AIDS patients
to measure the lymphocyte count on a regular basis.
Experts consulted by the United States Public Health
Service recommend the following frequency of serum
testing based on the patient’s CD4+ level:
CD4+ count more than 600 cells/mm3: Every six
months.



CD4+ count between 200-600 cells/mm3: Every
three months.



CD4+ count less than 200 cells/mm3: Every three
months.



When the CD4+ count falls below 200 cells/mm3,
the doctor will put the patient on a medication regimen to protect him or her against opportunistic
infections.
HIV VIRAL LOAD TESTS. Another type of blood test
for monitoring AIDS patients is the viral load test. It
supplements the CD4+ count, which can tell the doctor the extent of the patient’s loss of immune function,
but not the speed of HIV replication in the body. The
viral load test is based on PCR techniques and can
measure the number of copies of HIV nucleic acids.
Successive test results for a given patient’s viral load
are calculated on a base 10 logarithmic scale.
ORAL HIV TESTS. Scientists have developed oral
HIV tests that can be conducted with saliva samples.
One of the unintented effects of these tests is the
misperception that HIV can be transmitted through
saliva. Still, they present an excellent alternative to
blood sample testing.
RAPID HIV TESTS. Researchers constantly work on
more rapid tests for HIV that can be done in physician
offices or by less skilled people and more convenient
locations in developing countries. A finger-stick test
that can be read quickly from a whole blood sample
had shown promising results in the fall of 2003.

GALE ENCYCLOPEDIA OF MEDICINE

In 2004, a new three-minute test for HIV was
lunched in the United States under FDA approval.
The hope of this test is that health care providers
such as family practice physician offices can quickly
test a patient in the office and provide results while the
patient waits, rather than sending results to a lab.
BETA2-MICROGLOBULIN (BETA2M). Beta-microglo-

bulin is a protein found on the surface of all human
cells with a nucleus. It is released into the blood when a
cell dies. Although rising blood levels of 2M are found
in patients with cancer and other serious diseases, a
rising 2M blood level can be used to measure the
progression of AIDS.
P24 ANTIGEN CAPTURE ASSAY. Found in the viral
core of HIV, p24 is a protein that can be measured by
the ELISA technique. Doctors can use p24 assays to
measure the antiviral activity of the patient’s medications. In addition, the p24 assay is sometimes useful
in detecting HIV infection before seroconversion.
However, p24 is consistently present in only 25% of
persons infected with HIV.
GENOTYPIC DRUG RESISTANCE TEST. Genotypic
testing can help determine whether specific gene
mutations, common in people with HIV, are causing
drug resistance and drug failure. The test looks for
specific genetic mutations within the virus that are
known to cause resistance to certain drugs used in
HIV treatment. For example the drug 3TC, also
known as lamivudine (Epivir), is not effective against
strains of HIV that have a mutation at a particular
position on the reverse transcriptase protein—amino
acid 184—known as M184V (M!V, methionine to
valine). So if the genotypic resistance test shows a
mutation at position M184V, it is likely the person
is resistant to 3TC and not likely to respond to 3TC
treatment. Genotypic tests are only effective if the
person is already taking antiviral medication and if
the viral load is greater than 1,000 copies per milliliter
(mL) of blood. The cost of the test, usually between
$300 and $500, is usually now covered by many insurance plans.
PHENOTYPIC

DRUG

RESISTANCE

TESTING.

Phenotypic testing directly measures the sensitivity of
a patient’s HIV to particular drugs and drug combinations. To do this, it measures the concentration of a
drug required to inhibit viral replication in the test
GALE ENCYCLOPEDIA OF MEDICINE

tube. This is the same method used by researchers to
determine whether a drug might be effective against
HIV before using it in human clinical trials.
Phenotypic testing is a more direct measurement of
resistance than genotypic testing. Also, unlike genotypic testing, phenotypic testing does not require a high
viral load but it is recommended that persons already
be taking antiretroviral drugs. The cost is between $700
and $900 and is now covered by many insurance plans.
AIDS serology in children
Children born to HIV-infected mothers may
acquire the infection through the mother’s placenta
or during the birth process. Public health experts
recommend the testing and monitoring of all children
born to mothers with HIV. Diagnostic testing in children older than 18 months is similar to adult testing,
with ELISA screening confirmed by Western blot.
Younger infants can be diagnosed by direct culture
of the HIV virus, PCR testing, and p24 antigen testing.
These techniques allow a pediatrician to identify 50%
of infected children at or near birth, and 95% of cases
in infants three to six months of age.

Preparation
Preparation and aftercare are important parts of
AIDS diagnostic testing. Doctors are now advised to
take the patient’s emotional, social, economic, and
other circumstances into account and to provide counseling before and after testing. Patients are generally
better able to cope with the results if the doctor has
spent some time with them before the blood test
explaining the basic facts about HIV infection and
testing. Many doctors now offer this type of informational counseling before performing the tests.

Aftercare
If the test results indicate that the patient is HIVpositive, he or she will need counseling, information,
referral for treatment, and support. Doctors can either
counsel the patient themselves or invite an experienced
HIV counselor to discuss the results of the blood tests
with the patient. They also will assess the patient’s
emotional and psychological status, including the possibility of violent behavior and the availability of a
support network.

Risks
The risks of AIDS testing are primarily related to
disclosure of the patient’s HIV status rather than to
any physical risks connected with blood testing. Some
93

AIDS tests

Another test, called the VScan test kit, requires no
refrigeration or electricity and can safely be stored at
room temperature. Even if the positive results must be
confirmed by ELISA or Western blotting, an accurate
initial rapid test can help screen populations for HIV
antibodies.

Alanine aminotransferase test

patients are better prepared to cope with a positive
diagnosis than others, depending on their age, sex,
health, resources, belief system, and similar factors.

Weinhardt, Lance S., et al. ‘‘Human Immunodeficiency
Virus Testing and Behavior Change.’’ Archives of
Internal Medicine (May 22, 2000): 1538.

Ken R. Wells
Teresa G. Odle

Normal results
Normal results for ELISA, Western blot, IFA,
and PCR testing are negative for HIV antibody.
Normal results for blood cell counts:


WBC differential: Total lymphocytes 24-44% of the
white blood cells.



Hematocrit: 40-54% in men; 37-47% in women.

T cell lymphocytes: 644-2200/mm3, 60-88% of all
lymphocytes.



B cell lymphocytes: 82-392/mm3, 3-20% of all
lymphocytes.



CD4+ lymphocytes: 500-1200/mm3, 34-67% of all
lymphocytes.


Air embolism see Gas embolism

I Alanine aminotransferase test
Definition
The alanine aminotransferase test, also known as
ALT, is one of a group of tests known as liver function
tests (or LFTs) and is used to monitor damage to the
liver.

Purpose
Abnormal results
The following results in AIDS tests indicate progression of the disease:


Percentage of CD4+ lymphocytes: less than 20% of
all lymphocytes.



CD4+ lymphocyte count: less than 200 cells/mm3.



Viral load test: Levels more than 5000 copies/mL.



:-2-microglobulin: Levels more than 3.5 mg/dL.



P24 antigen: Measurable amounts in blood serum.

Resources
BOOKS

Bennett, Rebecca, and Erin, Charles A., editors. HIV and
AIDS Testing, Screening, and Confidentiality: Ethics,
Law, and Social Policy. Oxford, England: Oxford
University Press, 2001.
PERIODICALS

‘‘Finger-stick Test is Accurate and Acceptable to Women in
Thailand.’’ Drug Week (September 5, 2003): 168.
Kaplan, Edward H., and Glen A. Satten. ‘‘Repeat Screening
for HIV: When to Test and Why.’’ The Journal of the
American Medical Association.
Medical Devices & Surgical Technology Week (September
12, 2004): 102.
‘‘Researcher Developing Home Test Kit for HIV
Therapies.’’ Medical Devices & Surgical Technology
Week (December 23, 2001): 2.
‘‘Researchers Report New Ultra-sensitive AIDS Test.’’
Biotech Week (July 14, 2004): 246.
94

ALT levels are used to detect liver abnormalities.
Since the alanine aminotransferase enzyme is also
found in muscle, tests indicating elevated AST levels
might also indicate muscle damage. However, other
tests, such as the levels of the MB fraction of creatine
kinase should indicate whether the abnormal test
levels are because of muscle or liver damage.

Description
The alanine aminotransferase test (ALT) can
reveal liver damage. It is probably the most specific
test for liver damage. However, the severity of the liver
damage is not necessarily shown by the ALT test, since
the amount of dead liver tissue does not correspond to
higher ALT levels. Also, patients with normal, or
declining, ALT levels may experience serious liver
damage without an increase in ALT.
Nevertheless, ALT is widely used, and useful,
because ALT levels are elevated in most patients with
liver disease. Although ALT levels do not necessarily
indicate the severity of the damage to the liver, they
may indicate how much of the liver has been damaged.
ALT levels, when compared to the levels of a similar
enzyme, aspartate aminotransferase (AST), may provide important clues to the nature of the liver disease.
For example, within a certain range of values, a ratio
of 2:1 or greater for AST: ALT might indicate that a
patient suffers from alcoholic liver disease. Other diagnostic data may be gleaned from ALT tests to indicate
abnormal results.
GALE ENCYCLOPEDIA OF MEDICINE

Description

No special preparations are necessary for this test.

Aftercare
This test involves blood being drawn, probably
from a vein in the patient’s elbow. The patient should
keep the wound from the needle puncture covered
(with a bandage) until the bleeding stops. Patients
should report any unusual symptoms to their
physician.

Normal results
Normal values vary from laboratory to laboratory, and should be available to your physician at the
time of the test. An informal survey of some laboratories indicates many laboratories find values from
approximately seven to 50 IU/L to be normal.

Abnormal results
Low levels of ALT (generally below 300 IU/L)
may indicate any kind of liver disease. Levels above
1,000 IU/L generally indicate extensive liver damage
from toxins or drugs, viral hepatitis, or a lack of oxygen (usually resulting from very low blood pressure or
a heart attack). A briefly elevated ALT above 1,000
IU/L that resolves in 24-48 hours may indicate a
blockage of the bile duct. More moderate levels of
ALT (300-1,000IU/L) may support a diagnosis of
acute or chronic hepatitis.
It is important to note that persons with normal
livers may have slightly elevated levels of ALT. This is
a normal finding.
Michael V. Zuck, PhD

Albers-Schönberg disease see Osteopetroses

I Albinism
Definition
Albinism is an inherited condition present at
birth, characterized by a lack of pigment that normally
gives color to the skin, hair, and eyes. Many types of
albinism exist, all of which involve lack of pigment in
varying degrees. The condition, which is found in all
races, may be accompanied by eye problems and may
lead to skin cancer later in life.
GALE ENCYCLOPEDIA OF MEDICINE

Albinism is a rare disorder found in fewer than
five people per 100,000 in the United States and
Europe. Other parts of the world have a much higher
rate; for example, albinism is found in about 20 out of
every 100,000 people in southern Nigeria.
There are 10 types of the most common form of the
condition, known as ‘‘oculocutaneous albinism,’’ which
affects the eyes, hair, and skin. In its most severe form,
hair and skin remain pure white throughout life. People
with a less severe form are born with white hair and skin,
which turn slightly darker as they age. Everyone with
oculocutaneous albinism experiences abnormal flickering eye movements (nystagmus) and sensitivity to bright
light. There may be other eye problems as well, including poor vision and crossed or ‘‘lazy’’ eyes (strabismus).
The second most common type of the condition is
known as ‘‘ocular’’ albinism, in which only the eyes
lack color; skin and hair are normal. There are five
forms of ocular albinism; some types cause more problems–especially eye problems–than others.

Causes and symptoms
Every cell in the body contains a matched pair of
genes, one inherited from each parent. These genes act
as a sort of ‘‘blueprint’’ that guides the development of
a fetus.
Albinism is an inherited problem caused by a flaw
in one or more of the genes that are responsible for
directing the eyes and skin to make melanin (pigment).
As a result, little or no pigment is made, and the child’s
skin, eyes and hair may be colorless.
In most types of albinism, a recessive trait, the
child inherits flawed genes for making melanin from
both parents. Because the task of making melanin is
complex, there are many different types of albinism,
involving a number of different genes.
It’s also possible to inherit one normal gene and
one albinism gene. In this case, the one normal gene
provides enough information in its cellular blueprint
to make some pigment, and the child will have normal
skin and eye color. They ‘‘carry’’ one gene for albinism. About one in 70 people are albinism carriers, with
one flawed gene but no symptoms; they have a 50%
chance of passing the albinism gene to their child.
However, if both parents are carriers with one flawed
gene each, they have a 1 in 4 chance of passing on both
copies of the flawed gene to the child, who will have
albinism. (There is also a type of ocular albinism that
is carried on the X chromosome and occurs almost
exclusively in males because they have only one X
95

Albinism

Preparation

Albinism
A man with albinism stands with his normally pigmented father. (Photograph by Norman Lightfoot, Photo Researchers, Inc.
Reproduced by permission.)

chromosome and, therefore, no other gene for the trait
to override the flawed one.)
Symptoms of albinism can involve the skin, hair,
and eyes. The skin, because it contains little pigment,
appears very light, as does the hair.
Although people with albinism may experience a
variety of eye problems, one of the myths about albinism is that it causes people to have pink or red eyes. In
fact, people with albinism can have irises varying from
light gray or blue to brown. (The iris is the colored
portion of the eye that controls the size of the pupil,
the opening that lets light into the eye.) If people with
albinism seem to have reddish eyes, it’s because light is
being reflected from the back of the eye (retina) in
much the same way as happens when people are
photographed with an electronic flash.
People with albinism may have one or more of the
following eye problems:
96



They may be very far-sighted or near-sighted, and
may have other defects in the curvature of the lens of
the eye (astigmatism) that cause images to appear
unfocused.



They may have a constant, involuntary movement of
the eyeball called nystagmus.



They may have problems in coordinating the eyes in
fixing and tracking objects (strabismus), which may
lead to an appearance of having ‘‘crossed eyes’’ at
times. Strabismus may cause some problems with
depth perception, especially at close distances.



They may be very sensitive to light (photophobia)
because their irises allow ‘‘stray’’ light to enter their
eyes. It’s a common misconception that people with
albinism shouldn’t go out on sunny days, but wearing sunglasses can make it possible to go outside
quite comfortably.
GALE ENCYCLOPEDIA OF MEDICINE

Amino acids—Natural substances that are the
building blocks of protein. The body breaks down
the protein in food into amino acids, and then uses
these amino acids to create other proteins. The body
also changes amino acids into melanin pigment.
Astigmatism—An eye condition in which the lens
doesn’t focus light evenly on the retina, leading to
problems with visual sharpness.
Carrier—A person with one normal gene and one
faulty gene, who can pass on a condition to others
without actually having symptoms.
DNA—The abbreviation for ‘‘deoxyribonucleic
acid,’’ the primary carrier of genetic information
found in the chromosomes of almost all organisms. The entwined double structure allows the
chromosomes to be copied exactly during cell
division.
DOPA—The common name for a natural chemical
(3, 4-dihydroxyphenylalanine) made by the body
during the process of making melanin.
Enzyme—A protein that helps the body convert
one chemical substance to another.
Gene—The basic unit of genetic material carried in
a particular place on a chromosome. Genes are
passed on from parents to child when the sperm
and egg unite during conception.
Hairbulb—The root of a strand of hair from which
the color develops.
Hermansky-Pudlak Syndrome (HPS)—A rare type
of albinism characterized by a problem with blood
clotting and a buildup of waxy material in lungs
and intestines.
Melanin—Pigment made in the hair, skin and eyes.
Nystagmus—An involuntary back-and-forth movement of the eyes that is often found in albinism.
Strabismus—Crossed or ‘‘lazy’’ eyes, often found
in albinism.
Tyrosine—A protein building block found in a
wide variety of foods that is used by the body to
make melanin.
Tyrosinase—An enzyme in a pigment cell which
helps change tyrosine to DOPA during the process
of making melanin.

In addition to the characteristically light skin and
eye problems, people with a rare form of albinism
GALE ENCYCLOPEDIA OF MEDICINE

called Hermansky-Pudlak Syndrome (HPS) also
have a greater tendency to have bleeding disorders,
inflammation of the large bowel (colitis), lung (pulmonary) disease, and kidney (renal) problems.

Diagnosis
It’s not always easy to diagnose the exact type
of albinism a person has; there are two tests available that can identify only two types of the condition. Recently, a blood test has been developed that
can identify carriers of the gene for some types of
albinism; a similar test during amniocentesis can
diagnose some types of albinism in an unborn
child. A chorionic villus sampling test during the fifth
week of pregnancy may also reveal some types of
albinism.
The specific type of albinism a person has can be
determined by taking a good family history and examining the patient and several close relatives.
The ‘‘hairbulb pigmentation test’’ is used to identify carriers by incubating a piece of the person’s hair
in a solution of tyrosine, a substance in food which the
body uses to make melanin. If the hair turns dark, it
means the hair is making melanin (a ‘‘positive’’ test);
light hair means there is no melanin. This test is the
source of the names of two types of albinism: ‘‘ty-pos’’
and ‘‘ty-neg.’’
The tyrosinase test is more precise than the
hairbulb pigmentation test. It measures the rate at
which hair converts tyrosine into another chemical
(DOPA), which is then made into pigment. The hair
converts tyrosine with the help of a substance called
‘‘tyrosinase.’’ In some types of albinism, tyrosinase
doesn’t do its job, and melanin production breaks
down.

Treatment
There is no treatment that can replace the lack of
melanin that causes the symptoms of albinism.
Doctors can only treat, not cure, the eye problems
that often accompany the lack of skin color. Glasses
are usually needed and can be tinted to ease pain from
too much sunlight. There is no cure for involuntary
eye movements (nystagmus), and treatments for
focusing problems (surgery or contact lenses) are not
effective in all cases.
Crossed eyes (strabismus) can be treated during
infancy, using eye patches, surgery or medicine injections. Treatment may improve the appearance of the
eye, but it can do nothing to cure the underlying
condition.
97

Albinism

KEY TERMS

Alcohol-related neurologic disease

Patients with albinism should avoid excessive
exposure to the sun, especially between 10 a.m. and
2 p.m. If exposure can’t be avoided, they should use
UVA-UVB sunblocks with an SPF of at least 20.
Taking beta- carotene may help provide some skin
color, although it doesn’t protect against sun
exposure.

Prognosis
In the United States, people with this condition
can expect to have a normal lifespan. People with
albinism may experience some social problems
because of a lack of understanding on the part of
others. When a member of a normally dark-skinned
ethnic group has albinism, he or she may face some
very complex social challenges.
One of the greatest health hazards for people with
albinism is excessive exposure to sun without protection, which could lead to skin cancer. Wearing opaque
clothes and sunscreen rated SPF 20, people with albinism can safely work and play outdoors safely even
during the summer.

I Alcohol-related
neurologic
disease
Definition
Alcohol, or ethanol, is a poison with direct toxic
effects on nerve and muscle cells. Depending on
which nerve and muscle pathways are involved,
alcohol can have far-reaching effects on different
parts of the brain, peripheral nerves, and muscles,
with symptoms of memory loss, incoordination,
seizures, weakness, and sensory deficits. These different effects can be grouped into three main categories:
(1) intoxication due to the acute effects of ethanol, (2)
withdrawal syndrome from suddenly stopping drinking, and (3) disorders related to long-term or chronic
alcohol abuse. Alcohol-related neurologic disease
includes Wernicke-Korsakoff disease, alcoholic
cerebellar degeneration, alcoholic myopathy, alcoholic neuropathy, alcohol withdrawal syndrome
with seizures and delirium tremens, and fetal alcohol
syndrome.

Description
Prevention
Genetic counseling is very important to prevent
further occurrences of the conditon.
Resources
BOOKS

National Association for the Visually Handicapped. Larry:
A Book for Children with Albinism Going to School. New
York: National Association for the Visually
Handicapped.
ORGANIZATIONS

Albinism World Alliance. <http://www.albinism.org/awa.
html>.
American Foundation for the Blind. 15 W. 16th St., New
York, NY 10011. (800) AFB-LIND.
Hermansky-Pudlak Syndrome Network, Inc. One South
Road, Oyster Bay, NY 11771-1905. (800) 789-9477.
<appell@theonramp.net>.
National Organization for Albinism and Hypopigmentation
(NOAH). 1530 Locust St., #29, Philadelphia, PA 191024415. (800) 473-2310. <http://www.albinism.org>.

Carol A. Turkington

Acute excess intake of alcohol can cause drunkenness (intoxication) or even death, and chronic or longterm abuse leads to potentially irreversible damage to
virtually any level of the nervous system. Any given
patient with long-term alcohol abuse may have no
neurologic complications, a single alcohol-related disease, or multiple conditions, depending on the genes
they have inherited, how well nourished they are, and
other environmental factors, such as exposure to other
drugs or toxins.
Neurologic complications of alcohol abuse may also
result from nutritional deficiency, because alcoholics tend
to eat poorly and may become depleted of thiamine or
other vitamins important for nervous system function.
Persons who are intoxicated are also at higher risk for
head injury or for compression injuries of the peripheral
nerves. Sudden changes in blood chemistry, especially
sodium, related to alcohol abuse may cause central pontine myelinolysis, a condition of the brainstem in which
nerves lose their myelin coating. Liver disease complicating alcoholic cirrhosis may cause dementia, delirium, and
movement disorder.

Causes and symptoms

Albuterol see Bronchodilators
Alcohol abuse see Alcoholism
Alcohol dependence see Alcoholism
98

When a person drinks alcohol, it is absorbed by
blood vessels in the stomach lining and flows rapidly
throughout the body and brain, as ethanol freely
crosses the blood-brain barrier that ordinarily keeps
GALE ENCYCLOPEDIA OF MEDICINE

Abstinence—Refraining from the use of alcoholic
beverages.
Atrophy—A wasting or decrease in size of a muscle
or other tissue.
Cerebellum—The part of the brain involved in
coordination of movement, walking, and balance.
Degeneration—Gradual, progressive loss of nerve
cells.
Delirium—Sudden confusion with decreased or
fluctuating level of consciousness.
Delirium tremens— A complication that may
accompany alcohol withdrawal. The symptoms
include body shaking (tremulousness), insomnia,
agitation, confusion, hearing voices or seeing
images that are not really there (hallucinations),
seizures, rapid heart beat, profuse sweating, high
blood pressure, and fever.
Dementia—Loss of memory and other higher functions, such as thinking or speech, lasting six months
or more.
Myoglobinuria—Reddish urine caused by excretion of myoglobin, a breakdown product of muscle.
Myopathy—A disorder that causes weakening of
muscles.
Neuropathy—A condition affecting the nerves supplying the arms and legs. Typically, the feet and
hands are involved first. If sensory nerves are
involved, numbness, tingling, and pain are prominent, and if motor nerves are involved, the patient
experiences weakness.
Thiamine—A B vitamin essential for the body to
process carbohydrates and fats. Alcoholics may
suffer complications (including Wernike-Korsakoff
syndrome) from a deficiency of this vitamin.
Wernicke-Korsakoff syndrome—A combination of
symptoms, including eye-movement problems, tremors, and confusion, that is caused by a lack of the
B vitamin thiamine and may be seen in alcoholics.

large molecules from escaping from the blood vessel to
the brain tissue. Drunkenness, or intoxication, may
occur at blood ethanol concentrations of as low as
50-150 mg per dL in people who don’t drink.
Sleepiness, stupor, coma, or even death from respiratory depression and low blood pressure occur at
progressively higher concentrations.
GALE ENCYCLOPEDIA OF MEDICINE

Although alcohol is broken down by the liver,
the toxic effects from a high dose of alcohol are most
likely a direct result of alcohol itself rather than of its
breakdown products. The fatal dose varies widely
because people who drink heavily develop a tolerance to the effects of alcohol with repeated use. In
addition, alcohol tolerance results in the need for
higher levels of blood alcohol to achieve intoxicating
effects, which increases the likelihood that habitual
drinkers will be exposed to high and potentially toxic
levels of ethanol. This is particularly true when binge
drinkers fail to eat, because fasting decreases the rate
of alcohol clearance and causes even higher blood
alcohol levels.
When a chronic alcoholic suddenly stops drinking, withdrawal of alcohol leads to a syndrome of
increased excitability of the central nervous system,
called delirium tremens or ‘‘DTs.’’ Symptoms begin
six to eight hours after abstinence, and are most pronounced 24-72 hours after abstinence. They include
body shaking (tremulousness), insomnia, agitation,
confusion, hearing voices or seeing images that are
not really there (such as crawling bugs), seizures,
rapid heart beat, profuse sweating, high blood pressure, and fever. Alcohol-related seizures may also
occur without withdrawal, such as during active
heavy drinking or after more than a week without
alcohol.
Wernicke-Korsakoff syndrome is caused by
deficiency of the B-vitamin thiamine, and can also
be seen in people who don’t drink but have some
other cause of thiamine deficiency, such as chronic
vomiting that prevents the absorption of this vitamin.
A 2004 study demonstrated that alcohol-dependent
patients admitted to a detoxification facility had consumed significantly less thiamine than a comparison
group of healthy volunteers. Patients with this condition have the sudden onset of Wernicke encephalopathy; the symptoms include marked confusion,
delirium, disorientation, inattention, memory loss,
and drowsiness. Examination reveals abnormalities
of eye movement, including jerking of the eyes
(nystagmus) and double vision. Problems with balance make walking difficult. People may have trouble
coordinating their leg movements, but usually not
their arms. If thiamine is not given promptly,
Wernicke encephalopathy may progress to stupor,
coma, and death.
If thiamine is given and death averted, Korsakoff’s
syndrome may develop in some patients, who suffer
from memory impairment that leaves them unable to
remember events for a period of a few years before the
onset of illness (retrograde amnesia) and unable to
99

Alcohol-related neurologic disease

KEY TERMS

Alcohol-related neurologic disease

learn new information (anterograde amnesia). Most
patients have very limited insight into their memory
dysfunction and have a tendency to make up explanations for events they have forgotten (confabulation).
Severe alcoholism can cause cerebellar degeneration, a slowly progressive condition affecting portions
of the brain called the anterior and superior cerebellar
vermis, causing a wide-based gait, leg incoordination,
and an inability to walk heel-to-toe in tightrope fashion. The gait disturbance usually develops over several
weeks, but may be relatively mild for some time, and
then suddenly worsen after binge drinking or an unrelated illness.
Fetal alcohol syndrome occurs in infants born to
alcoholic mothers when prenatal exposure to ethanol
retards fetal growth and development. Affected
infants often have a distinctive appearance with a
thin upper lip, flat nose and mid-face, short stature
and small head size. Almost half are mentally
retarded, and most others are mildly impaired intellectually or have problems with speech, learning, and
behavior. Fetal alcohol syndrome is the leading cause
of mental retardation and many physicians warn that
there is no safe level of alcohol for a pregnant mother
to consume.
Alcoholic myopathy, or weakness secondary to
breakdown of muscle tissue, is also known as alcoholic
rhabdomyolysis or alcoholic myoglobinuria. Males
are affected by acute (sudden onset) alcoholic myopathy four times as often as females. Breakdown of
muscle tissue (myonecrosis), can come on suddenly
during binge drinking or in the first days of alcohol
withdrawal. In its mildest form, this breakdown may
cause no noticeable symptoms, but may be detected by
a temporary elevation in blood levels of an enzyme
found predominantly in muscle, the MM fraction of
creatine kinase.
The severe form of acute alcoholic myopathy is
associated with the sudden onset of muscle pain, swelling, and weakness; a reddish tinge in the urine caused
by myoglobin, a breakdown product of muscle
excreted in the urine; and a rapid rise in muscle
enzymes in the blood. Symptoms usually worsen over
hours to a few days, and then improve over the next
week to 10 days as the patient is withdrawn from
alcohol. Muscle symptoms are usually generalized,
but pain and swelling may selectively involve the
calves or other muscle groups. The muscle breakdown
of acute alcoholic myopathy may be worsened by
crush injuries, which may occur when people drink
so much that they compress a muscle group with
their body weight for a long time without moving, or
100

by withdrawal seizures with generalized muscle
activity.
In patients who abuse alcohol over many years,
chronic alcoholic myopathy may develop. Males and
females are equally affected. Symptoms include painless weakness of the limb muscles closest to the trunk
and the girdle muscles, including the thighs, hips,
shoulders, and upper arms. This weakness develops
gradually, over weeks or months, without symptoms
of acute muscle injury. Muscle atrophy, or decreased
bulk, may be striking. The nerves of the extremities
may also begin to break down, a condition known as
alcoholic peripheral neuropathy, which can add to the
person’s difficulty in moving.
The way in which alcohol destroys muscle tissue is
still not well understood. Proposed mechanisms
include muscle membrane changes affecting the transport of calcium, potassium, or other minerals;
impaired muscle energy metabolism; and impaired
protein synthesis. Alcohol is metabolized or broken
down primarily by the liver, with a series of chemical
reactions in which ethanol is converted to acetate.
Acetate is metabolized by skeletal muscle, and alcohol-related changes in liver function may affect skeletal muscle metabolism, decreasing the amount of
blood sugar available to muscles during prolonged
activity. Because not enough sugar is available to supply needed energy, muscle protein may be broken
down as an alternate energy source. However, toxic
effects on muscle may be a direct result of alcohol itself
rather than of its breakdown products.
Although alcoholic peripheral neuropathy may
contribute to muscle weakness and atrophy by injuring the motor nerves controlling muscle movement,
alcoholic neuropathy more commonly affects sensory
fibers. Injury to these fibers can cause tingling or burning pain in the feet, which may be severe enough to
interfere with walking. As the condition worsens, pain
decreases but numbness increases.

Diagnosis
The diagnosis of alcohol-related neurologic disease depends largely on finding characteristic symptoms and signs in patients who abuse alcohol. Other
possible causes should be excluded by the appropriate
tests, which may include blood chemistry, thyroid
function tests, brain MRI (magnetic resonance imaging) or CT (computed tomography scan), and/or
cerebrospinal fluid analysis.
Acute alcoholic myopathy can be diagnosed
by finding myoglobin in the urine and increased
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Acute management of alcohol intoxication, delirium tremens, and withdrawal is primarily supportive,
to monitor and treat any cardiovascular or respiratory
failure that may develop. In delirium tremens, fever
and sweating may necessitate treatment of fluid loss
and secondary low blood pressure. Agitation may be
treated with benzodiazepines such as chlordiazepoxide,
beta-adrenergic antagonists such as atenolol, or alpha
2-adrenergic agonists such as clonidine. Because
Wernicke’s syndrome is rapidly reversible with thiamine, and because death may intervene if thiamine is
not given promptly, all patients admitted for acute
complications of alcohol, as well as all patients with
unexplained encephalopathy, should be given intravenous thiamine.
Withdrawal seizures typically resolve without
specific anti-epileptic drug treatment, although status
epilepticus (continual seizures occurring without interruption) should be treated vigorously. Acute alcoholic
myopathy with myoglobinuria requires monitoring
and maintenance of kidney function, and correction
of imbalances in blood chemistry including potassium,
phosphate, and magnesium levels.
Chronic alcoholic myopathy and other chronic
conditions are treated by correcting associated nutritional deficiencies and maintaining a diet adequate in
protein and carbohydrate. The key to treating any
alcohol-related disease is helping the patient overcome
alcohol addiction. Behavioral measures and social supports may be needed in patients who develop broad
problems in their thinking abilities (dementia) or
remain in a state of confusion and disorientation
(delirium). People with walking disturbances may
benefit from physical therapy and assistive devices.
Doctors may also prescribe drugs to treat the pain
associated with peripheral neuropathy.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Complete recovery from Wernicke’s syndrome
may follow prompt administration of thiamine.
However, repeated episodes of encephalopathy or
prolonged alcohol abuse may cause persistent dementia or Korsakoff psychosis. Most patients recover fully
from acute alcoholic myopathy within days to weeks,
but severe cases may be fatal from acute kidney failure
and disturbances in heart rhythm secondary to
increased potassium levels. Recovery from chronic
alcoholic myopathy may occur over weeks to months
of abstinence from alcohol and correction of malnutrition. Cerebellar degeneration and alcoholic neuropathy may also improve to some extent with abstinence
and balanced diet, depending on the severity and duration of the condition.

Prevention
Prevention requires abstinence from alcohol.
Persons who consume small or moderate amounts of
alcohol might theoretically help prevent nutritional
complications of alcohol use with dietary supplements
including B vitamins. However, proper nutrition cannot protect against the direct toxic effect of alcohol or
of its breakdown products. Patients with any alcoholrelated symptoms or conditions, pregnant women,
and patients with liver or neurologic disease should
abstain completely. Persons with family history of
alcoholism or alcohol-related conditions may also be
at increased risk for neurologic complications of alcohol use.
Resources
PERIODICALS

‘‘Missouri Clinics Will Diagnose and Treat Fetal Alcohol
Syndrome.’’ Mental Health Weekly Digeste (June 7,
2004): 33.
Stacey, Philip S. ‘‘Preliminary Investigation of Thiamine and
Alcohol Intake in Clinical and Healthy Samples.’’
Psychological Reports (June 2004): 845–849.
ORGANIZATIONS

National Institute on Alcohol Abuse and Alcoholism. 6000
Executive Boulevard, Willco Building, Bethesda, MD
20892-7003. <http://silk.nih.gov/silk/niaaa1>.

Laurie Barclay, MD
Teresa G. Odle

Alcohol withdrawal see Withdrawal
syndromes
Alcoholic cerebellar disease see Alcoholrelated neurologic disease
101

Alcohol-related neurologic disease

creatine kinase and other blood enzymes released from
injured muscle. The surgical removal of a small piece
of muscle for microscopic analysis (muscle biopsy)
shows the scattered breakdown and repair of muscle
fibers. Doctors must rule out other acquired causes of
muscle breakdown, which include the abuse of drugs
such as heroin, cocaine, or amphetamines; trauma
with crush injury; the depletion of phosphate or potassium; or an underlying defect in the metabolism of
carbohydrates or lipids. In chronic alcoholic myopathy, serum creatine kinase often is normal, and muscle
biopsy shows atrophy, or loss of muscle fibers.
Electromyography (EMG) may show features characteristic of alcoholic myopathy or neuropathy.

Alcoholism

Alcoholic hepatitis see Hepatitis, alcoholic
Alcoholic rose gardener’s disease see
Sporotrichosis

I Alcoholism

Symptoms Of Co-Alcohol Dependence

Psychological distress manifested in symptoms such as anxiety, aggression,
anorexia nervosa, bulimia, depression, insomnia, hyperactivity, and suicidal
tendency
Psychosomatic illness (ailments that have no biological basis and clear up
after the co-alcoholism clears up)
Family violence or neglect
Alcoholism or other drug abuse

Definition
Alcoholism is the popular term for alcohol abuse
and alcohol dependence. These disorders involve
repeated life problems that can be directly attributed
to the use of alcohol. Both disorders can have serious
consequences, affecting an individual’s health and personal life, as well as having an impact on society at large.

Description
The effects of alcoholism are far reaching.
Alcohol affects every body system, causing a wide
range of health problems. Problems include poor
nutrition, memory disorders, difficulty with balance
and walking, liver disease (including cirrhosis and
hepatitis), high blood pressure, muscle weakness
(including the heart), heart rhythm disturbances,
anemia, clotting disorders, decreased immunity to
infections, gastrointestinal inflammation and irritation, acute and chronic problems with the pancreas,
low blood sugar, high blood fat content, interference
with reproductive fertility, and weakened bones.
On a personal level, alcoholism results in marital
and other relationship difficulties, depression, unemployment, child abuse, and general family dysfunction.
Alcoholism causes or contributes to a variety of
severe social problems including homelessness, murder, suicide, injury, and violent crime. Alcohol is a
contributing factor in at least 50% of all deaths from
motor vehicle accidents. In fact, about 100,000 deaths
occur each year due to the effects of alcohol, of which
50% are due to injuries of some sort. According to a
special report prepared for the U.S. Congress by the
National Institute on Alcohol Abuse and Alcoholism,
the impact of alcohol on society, including violence,
traffic accidents, lost work productivity, and premature death, costs our nation an estimated $185 billion
annually. In addition, it is estimated that approximately one in four children (19 million children or
29% of children up to 17 years of age) is exposed at
some time to familial alcohol abuse, alcohol dependence, or both. Furthermore, it has been estimated
that approximately 18% of adults experience an
102

episode of alcohol abuse or dependence a some time
during their lives.

Causes and symptoms
There are probably a number of factors that work
together to cause a person to become an alcoholic.
Recent genetic studies have demonstrated that close
relatives of an alcoholic are four times more likely to
become alcoholics themselves. Furthermore, this risk
holds true even for children who were adopted away
from their biological families at birth and raised in a
non-alcoholic adoptive family, with no knowledge of
their biological family’s difficulties with alcohol. More
research is being conducted to determine if genetic
factors could account for differences in alcohol metabolism that may increase the risk of an individual
becoming an alcoholic.
The symptoms of alcoholism can be broken down
into two major categories: symptoms of acute alcohol
use and symptoms of long-term alcohol use.
Immediate (acute) effects of alcohol use
Alcohol exerts a depressive effect on the brain. The
blood-brain barrier does not prevent alcohol from
entering the brain, so the brain alcohol level will quickly
become equivalent to the blood alcohol level. Alcohol’s
depressive effects result in difficulty walking, poor balance, slurring of speech, and generally poor coordination (accounting in part for the increased likelihood of
injury). The affected person also may have impairment
of peripheral vision. At higher alcohol levels, a person’s
breathing and heart rates will be slowed, and vomiting
may occur (with a high risk of the vomit being breathed
into the lungs, resulting in severe problems, including
the possibility of pneumonia). Still higher alcohol levels
may result in coma and death.
Effects of long-term (chronic) alcoholism
Long-term use of alcohol affects virtually every
organ system of the body:
GALE ENCYCLOPEDIA OF MEDICINE

Blood-brain barrier— A network of blood vessels
characterized by closely spaced cells that prevents
many potentially toxic substances from penetrating
the blood vessel walls to enter the brain. Alcohol is
able to cross this barrier.
Detoxification—The phase of treatment during
which a patient stops drinking and is monitored
and cared for while he or she experiences withdrawal from alcohol.
Relapse—A return to a disease state, after recovery
appeared to be occurring. In alcoholism, relapse
refers to a patient beginning to drink alcohol again
after a period of avoiding alcohol.
Tolerance—A phenomenon during which a drinker becomes physically accustomed to a particular
quantity of alcohol, and requires ever-increasing
quantities in order to obtain the same effects.



Blood. Alcohol can cause changes to all the types of
blood cells. Red blood cells become abnormally
large. White blood cells (important for fighting infections) decrease in number, resulting in a weakened
immune system. This places alcoholics at increased
risk for infections, and is thought to account in part
for the increased risk of cancer faced by alcoholics
(10 times the risk for nonalcoholics). Platelets and
blood clotting factors are affected, causing an
increased risk of bleeding.



Heart. Small amounts of alcohol cause a drop in
blood pressure, but with increased use, alcohol
begins to increase blood pressure into a dangerous
range. High levels of fats circulating in the bloodstream increase the risk of heart disease. Heavy
drinking results in an increase in heart size, weakening of the heart muscle, abnormal heart rhythms, a
risk of blood clots forming within the chambers of the
heart, and a greatly increased risk of stroke (due to a
blood clot from the heart entering the circulatory
system, going to the brain, and blocking a brain
blood vessel).



Reproductive system. Heavy drinking has a negative
effect on fertility in both men and women, by
decreasing testicle and ovary size, and interfering
with both sperm and egg production. When pregnancy is achieved in an alcoholic woman, the baby
has a great risk of being born with fetal alcohol
syndrome, which causes distinctive facial defects,
lowered IQ, and behavioral problems.

Withdrawal—Those signs and symptoms experienced by a person who has become physically
dependent on a drug, experienced upon decreasing
the drug’s dosage or discontinuing its use.





Nervous system. An estimated 30-40% of all men in
their teens and twenties have experienced alcoholic
blackout, which occurs when drinking a large quantity of alcohol results in the loss of memory of the
time surrounding the episode of drinking. Alcohol is
well-known to cause sleep disturbances, so that overall sleep quality is affected. Numbness and tingling
may occur in the arms and legs. Two syndromes,
which can occur together or separately, are known
as Wernicke’s and Korsakoff’s syndromes. Both are
due to the low thiamine (a form of vitamin B
complex) levels found in alcoholics. Wernicke’s
syndrome results in disordered eye movements, very
poor balance and difficulty walking, while
Korsakoff’s syndrome severely affects one’s memory,
preventing new learning from taking place.
Gastrointestinal system. Alcohol causes loosening of
the muscular ring that prevents the stomach’s contents from re-entering the esophagus. Therefore, the
acid from the stomach flows backward into the esophagus, burning those tissues, and causing pain and
bleeding. Inflammation of the stomach also can
result in bleeding and pain, and decreased desire to
eat. A major cause of severe, uncontrollable bleeding
(hemorrhage) in an alcoholic is the development
of enlarged (dilated) blood vessels within the

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Two different types of alcohol-related difficulties
have been identified. The first is called alcohol dependence, which refers to a person who literally depends
103

Alcoholism

esophagus, which are called esophageal varices.
These varices actually are developed in response to
liver disease, and are extremely prone to bursting and
hemorrhaging. Diarrhea is a common symptom, due
to alcohol’s effect on the pancreas. In addition,
inflammation of the pancreas (pancreatitis) is a serious and painful problem in alcoholics. Throughout
the intestinal tract, alcohol interferes with the
absorption of nutrients, creating a malnourished
state. Because alcohol is broken down (metabolized)
within the liver, the organ is severely affected by
constant levels of alcohol. Alcohol interferes with a
number of important chemical processes that also
occur in the liver. The liver begins to enlarge and fill
with fat (fatty liver), fibrous scar tissue interferes with
the liver’s normal structure and function (cirrhosis),
and the liver may become inflamed (hepatitis).

KEY TERMS

Alcoholism

on the use of alcohol. Three of the following traits
must be present to diagnose alcohol dependence:


tolerance, meaning that a person becomes accustomed to a particular dose of alcohol, and must
increase the dose in order to obtain the desired effect



withdrawal, meaning that a person experiences
unpleasant physical and psychological symptoms
when he or she does not drink alcohol



the tendency to drink more alcohol than one intends
(once an alcoholic starts to drink, he or she finds it
difficult to stop)



being unable to avoid drinking or stop drinking once
started



having large blocks of time taken up by alcohol use



choosing to drink at the expense of other important
tasks or activities



drinking despite evidence of negative effects on one’s
health, relationships, education, or job

Diagnosis is sometimes brought about when
family members call an alcoholic’s difficulties to the
attention of a physician. A clinician may begin to be
suspicious when a patient suffers repeated injuries or
begins to experience medical problems related to
the use of alcohol. In fact, some estimates suggest
that about 20% of a physician’s patients will be
alcoholics.
Diagnosis is aided by administering specific psychological assessments that try to determine what
aspects of a person’s life may be affected by his or
her use of alcohol. Determining the exact quantity of
alcohol that a person drinks is of much less importance than determining how his or her drinking affects
relationships, jobs, educational goals, and family life.
In fact, because the metabolism (how the body breaks
down and processes) of alcohol is so individual, the
quantity of alcohol consumed is not part of the criteria
list for diagnosing either alcohol dependence or alcohol abuse.
One simple tool for beginning the diagnosis of
alcoholism is called the CAGE questionnaire. It consists of four questions, with the first letters of each key
word spelling out the word CAGE:


Have you ever tried to Cut down on your drinking?



Have you ever been Annoyed by anyone’s comments
about your drinking?



Have you ever felt Guilty about your drinking?



Do you ever need an Eye-opener (a morning drink of
alcohol) to start the day)?

104

Other, longer lists of questions exist to help determine the severity and effects of a person’s alcohol use.
Given the recent research pointing to a genetic basis
for alcoholism, it is important to ascertain whether
anyone else in the person’s family has ever suffered
from alcoholism.

Treatment
Treatment of alcoholism has two parts. The first
step in the treatment of alcoholism, called detoxification, involves helping the person stop drinking and
ridding his or her body of the harmful (toxic) effects
of alcohol. Because the person’s body has become
accustomed to alcohol, the person will need to be
supported through withdrawal. Withdrawal will be
different for different patients, depending on the severity of the alcoholism, as measured by the quantity of
alcohol ingested daily and the length of time the
patient has been an alcoholic. Withdrawal symptoms
can range from mild to life-threatening. Mild withdrawal symptoms include nausea, achiness, diarrhea,
difficulty sleeping, sweatiness, anxiety, and trembling.
This phase is usually over in about three to five days.
More severe effects of withdrawal can include hallucinations (in which a patient sees, hears, or feels something that is not actually real), seizures, an unbearable
craving for more alcohol, confusion, fever, fast heart
rate, high blood pressure, and delirium (a fluctuating
level of consciousness). Patients at highest risk for the
most severe symptoms of withdrawal (referred to as
delirium tremens) are those with other medical
problems, including malnutrition, liver disease, or
Wernicke’s syndrome. Delirium tremens usually
begin about three to five days after the patient’s last
drink, progressing from the more mild symptoms to
the more severe, and may last a number of days.
Patients going through only mild withdrawal are
simply monitored carefully to make sure that more
severe symptoms do not develop. No medications are
necessary, however. Treatment of a patient suffering
the more severe effects of withdrawal may require the
use of sedative medications to relieve the discomfort of
withdrawal and to avoid the potentially life-threatening complications of high blood pressure, fast heart
rate, and seizures. Drugs called benzodiazapines are
helpful in those patients suffering from hallucinations.
Because of the patient’s nausea, fluids may need to be
given through a vein (intravenously), along with some
necessary sugars and salts. It is crucial that thiamine
be included in the fluids, because thiamine is usually
quite low in alcoholic patients, and deficiency of thiamine is responsible for the Wernicke-Korsakoff
syndrome.
GALE ENCYCLOPEDIA OF MEDICINE

Sessions led by peers, where recovering alcoholics
meet regularly and provide support for each other’s
recoveries, are considered among the best methods of
preventing a return to drinking (relapse). Perhaps the
most well-known such group is called Alcoholics
Anonymous, which uses a ‘‘12-step’’ model to help
people avoid drinking. These steps involve recognizing
the destructive power that alcohol has held over
the alcoholic’s life, looking to a higher power for
help in overcoming the problem, and reflecting on
the ways in which the use of alcohol has hurt others
and, if possible, making amends to those people.
According to a recent study reported by the American
Psychological Association (APA), anyone, regardless
of his or her religious beliefs or lack of religious beliefs,
can benefit from participation in 12-step programs
such as Alcoholics Anonymous (AA) or Narcotics
Anonymous (NA). The number of visits to 12-step
self-help groups exceeds the number of visits to all
mental health professionals combined.
There are also medications that may help an alcoholic avoid returning to drinking. These have been
used with variable success. Disulfiram (Antabuse)
is a drug which, when mixed with alcohol, causes
unpleasant reactions including nausea, vomiting,
diarrhea, and trembling. Naltrexone, along with a
similar compound, Nalmefene, can be helpful in limiting the effects of a relapse. Acamprosate is helpful in
preventing relapse. None of these medications would
be helpful unless the patient was also willing to work
very hard to change his or her behavior. In 2004, a new
compound was discovered that blocks actions of
chemicals in the brain that may lead to relapses.
Clinical tests were still underway, but development of
such a drug could have great potential in the medical
management of alcoholism. Another study that year
found that topiramate (Topamax), an antiseizure
medication, was effective in treating alcohol dependence in 150 participants in a clinical trial. The authors
called for further study of this possible treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
Alternative treatments can be a helpful adjunct
for the alcoholic patient, once the medical danger of
withdrawal has passed. Because many alcoholics
have very stressful lives (whether because of or leading to the alcoholism is sometimes a matter of
debate), many of the treatments for alcoholism
involve dealing with and relieving stress. These
include massage, meditation, and hypnotherapy. The
malnutrition of long-term alcohol use is addressed by
nutrition-oriented practitioners with careful attention to a healthy diet and the use of nutritional supplements such as vitamins A, B complex, and C, as
well as certain fatty acids, amino acids, zinc, magnesium, and selenium. Herbal treatments include milk
thistle (Silybum marianum), which is thought to protect the liver against damage. Other herbs are thought
to be helpful for the patient suffering through withdrawal. Some of these include lavender (Lavandula
officinalis), skullcap (Scutellaria lateriflora), chamomile (Matricaria recutita), peppermint (Mentha
piperita) yarrow (Achillea millefolium), and valerian
(Valeriana officinalis). Acupuncture is believed to
both decrease withdrawal symptoms and to help
improve a patient’s chances for continued recovery
from alcoholism.

Prognosis
Recovery from alcoholism is a life-long process.
In fact, people who have suffered from alcoholism are
encouraged to refer to themselves ever after as ‘‘a
recovering alcoholic,’’ never a recovered alcoholic.
This is because most researchers in the field believe
that since the potential for alcoholism is still part of
the individual’s biological and psychological makeup,
one can never fully recover from alcoholism. The
potential for relapse (returning to illness) is always
there, and must be acknowledged and respected.
Statistics suggest that, among middle-class alcoholics
in stable financial and family situations who have
undergone treatment, 60% or more can be successful
at an attempt to stop drinking for at least a year, and
many for a lifetime.

Prevention
Prevention must begin at a relatively young age
since the first instance of intoxication (drunkenness)
usually occurs during the teenage years. In fact, a 2004
study found that girls experimented with alcohol and
cigarettes at a younger age — 20% by seventh grage —
than boys. It is particularly important that teenagers
who are at high risk for alcoholism—those with a
105

Alcoholism

After cessation of drinking has been accomplished, the next steps involve helping the patient
avoid ever taking another drink. This phase of treatment is referred to as rehabilitation. The best programs
incorporate the family into the therapy, because the
family has undoubtedly been severely affected by the
patient’s drinking. Some therapists believe that family
members, in an effort to deal with their loved one’s
drinking problem, sometimes develop patterns of
behavior that accidentally support or ‘‘enable’’ the
patient’s drinking. This situation is referred to as
‘‘co-dependence,’’ and must be addressed in order to
successfully treat a person’s alcoholism.

Aldolase test

family history of alcoholism, an early or frequent use
of alcohol, a tendency to drink to drunkenness, alcohol use that interferes with school work, a poor family
environment, or a history of domestic violence —
receive education about alcohol and its long-term
effects. How this is best achieved, without irritating
the youngsters and thus losing their attention, is the
subject of continuing debate and study.
Resources
BOOKS

KEY TERMS
Aldolase—An enzyme, found primarily in the muscle, that helps convert sugar into energy.
Enzyme—A substance needed to trigger specific
chemical reactions.
Neurologic—Having to do with the nervous system.
Skeletal muscle—Muscle connected to, and necessary for the movement of, bones.

National Institute on Alcohol Abuse and Alcoholism. 10th
Special Report to the U.S. Congress on Alcohol and
Health. National Institute of Health, 2000.
PERIODICALS

Koch Kubetin, Sally. ‘‘Girls Before Boys in Cigarette and
Alcohol Use: Longitudinal Study.’’ Pediatric News
(March 2004): 29.
‘‘Research Findings Suggest Compound Might Help in
Fight Against Alcoholism.’’ Drug Week (January 9,
2004): 18.
Walling, Anne D. ‘‘Topiramate in the Treatment of Alcohol
Dependence.’’ American Family Physician (January 1,
2004): 195.
ORGANIZATIONS

Al-Anon, Alanon Family Group, Inc. P.O. Box 862, Midtown
Station, New York, NY 10018-0862. (800) 356-9996.
<http://www.recovery.org/aa>.
Alcoholics Anonymous. Grand Central Station, Box 459,
New York, NY 10163. <http://www.alcoholics-anonymous.org/>.
National Alliance on Alcoholism and Drug Dependence,
Inc. 12 West 21st St., New York, NY 10010. (212) 2066770.
National Clearinghouse for Alcohol and Drug Information.
11426 Rockville Pike, Suite 200, Rockville, MD. 20852.
(800) 729-6686. <http:\\www.health.org>.
National Institute on Alcohol Abuse and Alcoholism
(NIAAA). 6000 Executive Boulevard, Bethesda,
Maryland 20892-7003. <http://www.niaaa.nih.gov>.

Bill Asenjo, MS, CRC
Teresa G. Odle

ALD see Adrenoleukodystrophy

I Aldolase test
Definition
Aldolase is an enzyme found throughout the
body, particularly in muscles. Like all enzymes, it is
needed to trigger specific chemical reactions. Aldolase
106

helps muscle turn sugar into energy. Testing for aldolase is done to diagnose and monitor skeletal muscle
diseases.

Purpose
Skeletal muscle diseases increase the aldolase level
found in a person’s blood. Skeletal muscles are those
muscles attached to bones and whose contractions
make those bones move. When the muscles are diseased or damaged, such as in muscular dystrophy, the
cells deteriorate and break open. The contents of the
cells, including aldolase, spill into the bloodstream.
Measuring the amount of aldolase in the blood indicates the degree of muscle damage.
As muscles continue to deteriorate, aldolase levels
decrease and eventually fall below normal. Less muscle means fewer cells and less aldolase.
Muscle weakness may be caused by neurologic as
well as muscular problems. The measurement of
aldolase levels can help pinpoint the cause. Aldolase
levels will be normal where muscle weakness is caused
by neurological disease, such as poliomyelitis or
multiple sclerosis, but aldolase levels will be elevated
in cases of muscular disease, such as muscular
dystrophy.
Aldolase is also found in the liver and cardiac
muscle of the heart. Damage or disease to these
organs, such as chronic hepatitis or a heart attack,
will also increase aldolase levels in the blood, but to a
lesser degree.

Description
Aldolase is measured by mixing a person’s serum
with a substance with which aldolase is known to
trigger a reaction. The end product of this reaction is
measured, and, from that measurement, the amount of
aldolase in the person’s serum is determined.
GALE ENCYCLOPEDIA OF MEDICINE

I Aldosterone assay
Definition

Preparation
To collect the 5-10 ml of blood needed for this test,
a healthcare worker ties a tourniquet on the patient’s
upper arm, locates a vein in the inner elbow region, and
inserts a needle into that vein. Vacuum action draws
the blood through the needle into an attached tube.
Collection of the sample takes only a few minutes.
The patient should avoid strenuous exercise and
have nothing to eat or drink, except water, for eight to
ten hours before this test.

Aftercare
Discomfort or bruising may occur at the puncture
site and the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops will reduce
bruising. Warm packs to the puncture site will relieve
discomfort.

Normal results
Newborns have the highest normal aldolase levels
and adults the lowest. Normal values will vary based
on the laboratory and the method used.

Abnormal results
As noted, aldolase is elevated in skeletal muscle
diseases, such as muscular dystrophies. Duchenne’s
muscular dystrophy, the most common type of muscular dystrophy, will increase the aldolase level more
than any other disease.
Nondisease conditions that affect the muscle, such
as injury, gangrene, or an infection, can also increase
the aldolase level. Also, strenuous exercise can temporarily increase a person’s aldolase level.
Certain medications can increase the aldolase
level, while others can decrease it. To interpret what
the results of the aldolase test mean, a physician will
evaluate the result, the person’s clinical symptoms,
and other tests that are more specific for muscle
damage and disease.
Resources
BOOKS

Mayo Medical Laboratories. Interpretive Handbook.
Rochester, MN: Mayo Medical Laboratories, 1997.

Nancy J. Nordenson
GALE ENCYCLOPEDIA OF MEDICINE

This test measures the levels of aldosterone, a
hormone produced by the outer part (cortex) of the
two adrenal glands, organs which sit one on top of
each of the kidneys. Aldosterone regulates the
amounts of sodium and potassium in the blood. This
helps maintain water balance and blood volume,
which, in turn, affects blood pressure.

Purpose
Aldosterone measurement is useful in detecting a
condition called aldosteronism, which is caused by
excess secretion of the hormone from the adrenal
glands. There are two types of aldosteronism: primary
and secondary. Primary aldosteronism is most commonly caused by an adrenal tumor, as in Conn’s
syndrome. Idiopathic (of unknown cause) hyperaldosteronism is another type of primary aldosteronism.
Secondary aldosteronism is more common and may
occur with congestive heart failure, cirrhosis with fluid
in the abdominal cavity (ascites), certain kidney diseases, excess potassium, sodium-depleted diet, and
toxemia of pregnancy.
To differentiate primary aldosteronism from secondary aldosteronism, a plasma renin test should be
performed at the same time as the aldosterone assay.
Renin, an enzyme produced in the kidneys, is high in
secondary aldosteronism and low in primary
aldosteronism.

Description
Aldosterone testing can be performed on a blood
sample or on a 24-hour urine specimen. Several factors, including diet, posture (upright or lying down),
and time of day that the sample is obtained can cause
aldosterone levels to fluctuate. Blood samples are
affected by short-term fluctuations. A urine specimen
collected over an entire 24-hour period lessens the
effects of those interfering factors and provides a
more reliable aldosterone measurement.

Preparation
Fasting is not required for either the blood sample
or urine collection, but the patient should maintain a
normal sodium diet (approximately 0.1 oz [3g]/day)
for at least two weeks before either test. The doctor
should decide if drugs that alter sodium, potassium,
and fluid balance (e.g., diuretics, antihypertensives,
107

Aldosterone assay

The test is covered by insurance when medically
necessary. Results are usually available the next day.

Alemtuzumab

Abnormal results

KEY TERMS
Aldosteronism—A condition in which the adrenal
glands secrete excessive levels of the hormone
aldosterone.
Renin—An enzyme produced in the kidneys that
controls the activation of the hormone angiotensin,
which stimulates the adrenal glands to produce
aldosterone.

steroids, oral contraceptives) should be withheld. The
test will be more accurate if these are suspended at
at least two weeks before the test. Renin inhibitors
(e.g., propranolol) should not be taken one week
before the test, unless permitted by the physician.
The patient should avoid licorice for at least two
weeks before the test, because of its aldosterone-like
effect. Strenuous exercise and stress can increase
aldosterone levels as well. Because the test is usually
performed by a method called radioimmunoassay,
recently administered radioactive medications will
affect test results.
Since posture and body position affect aldosterone, hospitalized patients should remain in an
upright position (at least sitting) for two hours
before blood is drawn. Occasionally blood will be
drawn again before the patient gets out of bed.
Nonhospitalized patients should arrive at the laboratory in time to maintain an upright position for at
least two hours.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting
or feeling lightheaded after venipuncture, or hematoma (blood accumulating under the puncture site).

Normal results
Normal results are laboratory-specific and also
vary with sodium intake, with time of day, source of
specimen (e.g., peripheral vein, adrenal vein, 24-hour
urine), age, sex, and posture.
Reference ranges for blood include:


supine (lying down): 3-10 ng/dL



upright (sitting for at least two hours): Female:
5-30ng/dL; Male: 6-22 ng/dL.
Reference ranges for urine: 2-80 mg/24 hr.

108

Increased levels of aldosterone are found in Conn’s
disease (aldosterone-producing adrenal tumor), and in
cases of Bartter’s syndrome (a condition in which the
kidneys overexcrete potassium, sodium and chloride,
resulting in low blood levels of potassium and high
blood levels of aldosterone and renin). Among other
conditions, elevated levels are also seen in secondary
aldosteronism, stress, and malignant hypertension.
Decreased levels of aldosterone are found in
aldosterone deficiency, steroid therapy, high-sodium
diets, certain antihypertensive therapies, and
Addison’s disease (an autoimmune disorder).
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

I Alemtuzumab
Definition
Alemtuzumab is sold as Campath in the United
States. Alemtuzumab is a humanized monoclonal
antibody that selectively binds to CD52, a protein
found on the surface of normal and malignant B and
T cells, that is used to reduce the numbers of circulating malignant cells of patients who have B-cell chronic
lymphocytic leukemia (B-CLL).

Purpose
Alemtuzumab is a monoclonal antibody used to
treat B-CLL, one of the most prevalent forms of adult
chronic leukemia. It specifically binds CD52, a protein
found on the surface of essentially all B and T cells of
the immune system. By binding the CD52 protein on
the malignant B cells, the antibody targets it for
removal from the circulation. Scientists believe that
alemtuzumab triggers antibody-mediated lysis of the
B cells, a method that the immune system uses to
eliminate foreign cells.
Alemtuzumab has been approved by the FDA for
treatment of refractory B-CLL. For a patient’s disease
to be classified as refractory, both alkylating agents
and fludarabine treatment must have been tried and
failed. Thus, this drug gives patients who have tried all
GALE ENCYCLOPEDIA OF MEDICINE

Alkylating agent—A chemical that alters the composition of the genetic material of rapidly dividing cells,
such as cancer cells, causing selective cell death;
used as a chemotherapeutic agent to treat B-CLL.
Antibody—A protective protein made by the
immune system in response to an antigen, also
called an immunoglobulin.
Autoimmune—An immune reaction of a patient
against their own cells.
Humanization—Fusing the constant and variable
framework region of one or more human immunoglobulins with the binding region of an animal
immunoglobulin, done to reduce human reaction
against the fusion antibody.
Monoclonal—Genetically engineered antibodies
specific for one antigen.
Tumor lysis syndrome—A side effect of some immunotherapies, like monoclonal antibodies, that lyse
the tumor cells, due to the toxicity of flooding the
bloodstream with such a quantity of cellular contents.

approved treatments for B-CLL another option. As
most patients with B-CLL are in stage III or IV by the
time both alkylating agents and fludarabine have been
tried, the experience with alemtuzumab treatment are
primarily with those stages of the disease. In clinical
trials, about 30% of patients had a partial response to
the drug, with 2% of these being complete responses.
This antibody has been tested with limited success in the treatment of non-Hodgkin’s lymphoma
(NHL) and for the preparation of patients with various immune cell malignancies for bone marrow
transplantation. There is also a clinical trial ongoing
to test the ability of this antibody to prevent rejection
in kidney transplantation.

Description
Alemtuzumab is produced in the laboratory using
genetically engineered single clones of B-cells. Like all
antibodies, it is a Y-shaped molecule can bind one
particular substance, the antigen for that monoclonal
antibody. For alemtuzumab, the antigen is CD52, a
protein found on the surface of normal and malignant
B and T cells as well as other cells of the immune and
male reproductive systems. Alemtuzumab is a humanized antibody, meaning that the regions that bind
CD52, located on the tips of the Y branches, are
GALE ENCYCLOPEDIA OF MEDICINE

derived from rat antibodies, but the rest of the antibody is human sequence. The presence of the human
sequences helps to reduce the immune response by the
patient against the antibody itself, a problem seen
when complete mouse antibodies are used for cancer
therapies. The human sequences also help to ensure
that the various cell-destroying mechanisms of the
human immune system are properly triggered with
binding of the antibody.
Alemtuzumab was approved in May of 2001 for the
treatment of refractory B-CLL. It is approved for use
alone but clinical trials have tested the ability of the antibody to be used in combination with the purine analogs
pentostatin, fludarabine, and cladribine, and rituximab,
a monoclonal antibody specific for the CD20 antigen,
another protein found on the surface of B cells.

Recommended dosage
This antibody should be administered in a gradually escalating pattern at the start of treatment and any
time administration is interrupted for seven or more
days. The recommended beginning dosage for B-CLL
patients is a daily dose of 3 mg of Campath administered as a two-hour IV infusion. Once this amount is
tolerated, the dose is increased to 10 mg per day. After
tolerating this dose, it can be increased to 30 mg, administered three days a week. Acetominophen and diphenhydramine hydrochoride are given thirty to sixty
minutes before the infusion to help reduce side effects.
Additionally, patients generally receive anti-infective medication before treatment to help minimize the
serious opportunistic infections that can result from this
treatment. Specifically, trimethoprim/sulfamethoxazole
(to prevent bacterial infections) and famciclovir (to prevent viral infections) were used during the clinical trial to
decrease infections, although they were not eliminated.

Precautions
Blood studies should be done on a weekly basis while
patients are receiving the alemtuzumab treatment.
Vaccination during the treatment session is not recommended, given the T cell depletion that occurs during
treatment. Furthermore, given that antibodies like alumtuzumab can pass through the placenta to the developing
fetus and in breast milk, use during pregnancy and breastfeeding is not recommended unless clearly needed.

Side effects
A severe side effect of alemtuzumab treatment is
the possible depletion of one or more types of blood
109

Alemtuzumab

KEY TERMS

Alexander technique

cells. Because CD52 is expressed on a patient’s normal
B and T cells, as well as on the surface of the abnormal
B cells, the treatment eliminates both normal and
cancerous cells. The treatment also seems to trigger
autoimmune reactions against various other blood
cells. This results in severe reduction of the many
circulating blood cells including red blood cells (anemia), white blood cells (neutropenia), and clotting cells
(thrombopenia). These conditions are treated with
blood transfusions. The great majority of patients
treated exhibit some type of blood cell depletion.
A second serious side effect of this drug is the
prevalence of opportunistic infections that occurs during the treatment. Serious, and sometimes fatal bacterial, viral, fungal, and protozoan infections have
been reported. Treatments to prevent pneumonia and
herpes infections reduce, but do not eliminate these
infections.
The majority of other side effects occur after or
during the first infusion of the drug. Some common
side effects of this drug include fever and chills, nausea
and vomiting, diarrhea, shortness of breath, skin rash,
and unusual fatigue. This drug can also cause low
blood pressure (hypotension).
In patients with high tumor burden (a large number of circulating malignant B cells) this drug can
cause a side effect called tumor lysis syndrome.
Thought to be due to the release of the lysed cells’
contents into the blood stream, it can cause a misbalance of urea, uric acid, phosphate, potassium, and
calcium in the urine and blood. Patients at risk for
this side effect must keep hydrated and can be given
allopurinol before infusion.

Purpose
Because the Alexander technique helps students
improve overall functioning, both mental and physical, it offers a wide range of benefits. Nikolaas
Tinbergen, in his 1973 Nobel lecture, hailed the ‘‘striking improvements in such diverse things as high blood
pressure, breathing, depth of sleep, overall cheerfulness and mental alertness, resilience against outside
pressures, and the refined skill of playing a musical
instrument.’’ He went on to quote a list of other conditions helped by the Alexander technique: ‘‘rheumatism, including various forms of arthritis, then
respiratory troubles, and even potentially lethal
asthma; following in their wake, circulation defects,
which may lead to high blood pressure and also to
some dangerous heart conditions; gastrointestinal disorders of many types, various gynecological conditions, sexual failures, migraines and depressive states.’’
Literature in the 1980s and 1990s went on to
include improvements in back pain, chronic pain, postural problems, repetitive strain injury, benefits during
pregnancy and childbirth, help in applying physical
therapy and rehabilitative exercises, improvements in
strain caused by computer use, improvements in the
posture and performance of school children, and
improvements in vocal and dramatic performance
among the benefits offered by the technique.

Description

Interactions
There have been no formal drug interaction studies done for alemtuzumab.
Michelle Johnson, MS, JD

Alendronate see Bone disorder drugs

I Alexander technique
Definition
The Alexander technique is a somatic method
for improving physical and mental functioning.
Excessive tension, which Frederick Alexander, the
originator, recognized as both physical and mental,
110

restricts movement and creates pressure in the joints,
the spine, the breathing mechanism, and other organs.
The goal of the technique is to restore freedom and
expression to the body and clear thinking to the mind.

Origins
Frederick Matthias Alexander was born in 1869 in
Tasmania, Australia. He became an actor and
Shakespearean reciter, and early in his career he
began to suffer from strain on his vocal chords. He
sought medical attention for chronic hoarseness, but
after treatment with a recommended prescription and
extensive periods of rest, his problem persisted.
Alexander realized that his hoarseness began
about an hour into a dramatic performance and
reasoned that it was something he did in the process
of reciting that caused him to lose his voice. Returning
to his medical doctor, Alexander told him of his
observation. When the doctor admitted that he
didn’t know what Alexander was doing to injure
his vocal chords, Alexander decided to try and find
out for himself.
GALE ENCYCLOPEDIA OF MEDICINE

Direction—Bringing about the free balance of the
head on the spine and the resulting release of the
erector muscles of the back and legs which establish improved coordination.
Habit—Referring to the particular set of physical
and mental tensions present in any individual.
Inhibition—Referring to the moment in an
Alexander lesson when the student refrains from
beginning a movement in order to avoid tensing
of the muscles.
Sensory awareness—Bringing attention to the sensations of tension and/or release in the muscles.

Thus began a decade of self-observation and discovery. Using as many as three mirrors to observe himself in
the act of reciting, normal speaking, and later standing,
walking, and sitting, Alexander managed to improve
his coordination and to overcome his vocal problems.
One of his most startling discoveries was that in order to
change the way he used his body he had to change the
way he was thinking, redirecting his thoughts in such a
way that he did not produce unnecessary tension
when he attempted speech or movement. After making
this discovery at the end of the nineteenth century,
Alexander became a pioneer in body-mind medicine.
At first, performers and dancers sought guidance
from Alexander to overcome physical complaints and
to improve the expression and spontaneity of their
performances. Soon a great number of people sought
help from his teaching for a variety of physical and
mental disorders.
The Alexander technique is primarily taught oneon-one in private lessons. Introductory workshops or
workshops for special applications of the technique
(e.g.,workshops for musicians) are also common.
Private lessons range from a half-hour to an hour in
length, and are taught in a series. The number of lessons
varies according to the severity of the student’s difficulties with coordination or to the extent of the student’s
interest in pursuing the improvements made possible by
continued study. The cost of lessons ranges from $40-80
per hour. Insurance coverage is not widely available,
but discounts are available for participants in some
complementary care insurance plans. Pre-tax Flexible
Spending Accounts for health care cover Alexander
technique lessons if they are prescribed by a physician.
In lessons teachers guide students through simple
movements (while students are dressed in comfortable
GALE ENCYCLOPEDIA OF MEDICINE

clothing) and use their hands to help students identify
and stop destructive patterns of tension. Tensing
arises from mental processes as well as physical, so
discussions of personal reactions or behavior are likely
to arise in the course of a lesson.
The technique helps students move with ease and
improved coordination. At the beginning of a movement (the lessons are a series of movements), most people pull back their heads, raise their shoulders toward
their ears, over-arch their lower backs, tighten their legs,
and otherwise produce excessive tension in their bodies.
Alexander referred to this as misuse of the body.
At any point in a movement, proper use can be
established. If the neck muscles are not over-tensed,
the head will carry slightly forward of the spine, simply
because it is heavier in the front. When the head is out
of balance in the forward direction, it sets off a series
of stretch reflexes in the extensor muscles of the back.
It is skillful use of these reflexes, along with reflex
activity in the feet and legs, the arms and hands, the
breathing mechanism, and other parts of the body,
that lessons in the technique aim to develop.
Alexander found that optimal functioning of the
body was very hard to maintain, even for the short
period of time it took to complete a single movement.
People, especially adults, have very strong tension
habits associated with movement. Chronic misuse of
the muscles is common. It may be caused by slouching
in front of televisions or video monitors, too much
sitting or driving and too little walking, or by tension
associated with past traumas and injuries. Stiffening
the neck after a whiplash injury or favoring a broken or
sprained leg long after it has healed are examples of
habitual tension caused by injury.
The first thing a teacher of the Alexander technique does is to increase a student’s sensory awareness
of this excessive habitual tension, particularly that in
the neck and spine. Next the student is taught to
inhibit the tension. If the student prepares to sit
down, for example, he will tense his muscles in his
habitual way. If he is asked to put aside the intention
to sit and instead to free his neck and allow less constriction in his muscles, he can begin to change his
tense habitual response to sitting.
By leaving the head resting on the spine in its
natural free balance, by keeping eyes open and
focused, not held in a tense stare, by allowing the
shoulders to release, the knees to unlock and the
back to lengthen and widen, a student greatly reduces
strain. In Alexander lessons students learn to direct
themselves this way in activity and become skilled in
fluid, coordinated movement.
111

Alexander technique

KEY TERMS

Alkaline phosphatase test

Precautions

Resources

Side effects

BOOKS

The focus of the Alexander technique is educational. Teachers use their hands simply to gently guide
students in movement. Therefore, both contraindications and potential physiological side effects are kept
to a minimum. No forceful treatment of soft tissue or
bony structure is attempted, so damage to tissues, even
in the case of errors in teaching, is unlikely.
As students’ sensory awareness develops in the
course of Alexander lessons, they become more
acutely aware of chronic tension patterns. As students
learn to release excessive tension in their muscles and
to sustain this release in daily activity, they may
experience tightness or soreness in the connective tissue. This is caused by the connective tissue adapting to
the lengthened and released muscles and the expanded
range of movement in the joints.
Occasionally students may get light-headed during a lesson as contracted muscles release and effect
the circulatory or respiratory functioning.
Forceful contraction of muscles and rigid postures often indicate suppression of emotion. As muscles release during or after an Alexander lesson,
students may experience strong surges of emotion or
sudden changes in mood. In some cases, somatic memories surface, bringing to consciousness past injury or
trauma. This can cause extreme anxiety, and referrals
may be made by the teacher for counseling.

Dimon, Theodore. THE UNDIVIDED SELF: Alexander
Technique and the Control of Stress. North Atlantic
Books: 1999.
ORGANIZATIONS

Alexander Technique International, 1692 Massachusetts
Ave., 3rd Floor, Cambridge, MA 02138 USA. (888)
321-0856. Fax: 617-497-2615. ati@ati-net.com.
<http://www.ati-net.com>.
OTHER

Alexander Technique Resource Guide. (Includes list of
teachers) AmSAT Books. (800) 473-0620 or (804)
295-2840.

Sandra Bain Cushman

Alkali-resistant hemoglobin test see Fetal
hemoglobin test

I Alkaline phosphatase test
Definition
Alkaline phosphatase is an enzyme found
throughout the body. Like all enzymes, it is needed,
in small amounts, to trigger specific chemical reactions. When it is present in large amounts, it may
signify bone or liver disease or a tumor.

Research and general acceptance
Alexander became well known among the intellectual, artistic, and medical communities in London,
England, during the first half of the twentieth century.
Among Alexander’s supporters were John Dewey,
Aldous Huxley, Bernard Shaw, and renowned scientists Raymond Dart, G.E. Coghill, Charles
Sherrington, and Nikolaas Tinbergen.
Researchers continue to study the effects and
applications of the technique in the fields of education,
preventive medicine, and rehabilitation. The
Alexander technique has proven an effective treatment
for reducing stress, for improving posture and performance in schoolchildren, for relieving chronic pain,
and for improving psychological functioning. The
technique has been found to be as effective as betablocker medications in controlling stress responses in
professional musicians, to enhance respiratory function in normal adults, and to mediate the effects of
scoliosis in adolescents and adults.
112

Purpose
Medical testing of alkaline phosphatase is concerned with the enzyme that is found in liver, bone,
placenta, and intestine. In a healthy liver, fluid containing alkaline phosphate and other substances is
continually drained away through the bile duct. In a
diseased liver, this bile duct is often blocked, keeping
fluid within the liver. Alkaline phosphatase accumulates and eventually escapes into the bloodstream.
The alkaline phosphatase of the liver is produced by
the cells lining the small bile ducts (ductoles) in the liver.
Its origin differs from that of other enzymes called
aminotransferases. If the liver disease is primarily of
an obstructive nature (cholestatic), i.e. involving the
biliary drainage system, the alkaline phosphatase will
be the first and foremost enzyme elevation. If, on the
other hand, the disease is primarily of the liver cells
(hepatocytes), the aminotransferases will rise prominently. Thus, these enzymes are very useful in
GALE ENCYCLOPEDIA OF MEDICINE

Alkaline phosphatase—An enzyme found throughout the body, primarily in liver, bone, placenta, and
intestine.
Cholestatis—Stoppage or suppression of the flow
of bile.
Enzyme—A substance needed to trigger specific
chemical reactions.
Hepatocellular—Of or pertaining to liver cells.
Hepatocyte—A liver cell.
Isoenzyme—A variation of an enzyme.

distinguishing the type of liver disease–cholestatic or
hepatocellular.
Growing bones need alkaline phosphatase. Any
condition of bone growth will cause alkaline phosphatase levels to rise. The condition may be normal, such
as a childhood growth spurt or the healing of a broken
bone; or the condition may be a disease, such as bone
cancer, Paget’s disease, or rickets.
During pregnancy, alkaline phosphatase is made
by the placenta and leaks into the mother’s bloodstream. This is normal. Some tumors, however, start
production of the same kind of alkaline phosphatase
produced by the placenta. These tumors are called
germ cell tumors and include testicular cancer and
certain brain tumors.
Alkaline phosphatase from the intestine is
increased in a person with inflammatory bowel disease, such as ulcerative colitis.

Description
Alkaline phosphatase is measured by combining
the person’s serum with specific substances with which
alkaline phosphatase is known to react. The end
product of this reaction is measured; and from that
measurement, the amount of alkaline phosphatase in
the person’s serum is determined.
Each tissue–liver, bone, placenta, and intestine–
produces a slightly different alkaline phosphatase.
These variations are called isoenzymes. In the laboratory, alkaline phosphatase is measured as the total
amount or the amount of each of the the four isoenzymes. The isoenzymes react differently to heat, certain chemicals, and other processes in the laboratory.
Methods to measure them separately are based on
these differences.
GALE ENCYCLOPEDIA OF MEDICINE

The test is covered by insurance when medically
necessary. Results are usually available the next day.

Preparation
To collect the 5-10 ml blood needed for this test, a
healthcare worker ties a tourniquet on the person’s
upper arm, locates a vein in the inner elbow region,
and inserts a needle into that vein. Vacuum action
draws the blood through the needle into an attached
tube. Collection of the sample takes only a few minutes.
A person being tested for alkaline phosphatase
should not have anything to eat or drink, except
water, for eight to ten hours before the test. Some
people release alkaline phosphatase from the intestine
into the bloodstream after eating. This will temporarily increase the result of the test.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops will reduce
bruising. Warm packs to the puncture site will relieve
discomfort.

Normal results
Normal results vary by age and by sex. They also
vary based on the laboratory and the method used.

Abnormal results
Bone and liver disease increase alkaline phosphatase more than any other disease, up to five times the
normal level. Irritable bowel disease, germ cell tumors,
and infections involving the liver, such as viral hepatitis and infectious mononucleosis, increase the enzyme
also, but to a lesser degree. Healing bones, pregnancy,
and normal growth in children also increase levels.
Resources
BOOKS

Lehmann, Craig A., editor. Saunders Manual of Clinical
Laboratory Science. Philadelphia: W. B. Saunders
Co., 1998.

Nancy J. Nordenson

Alkalosis see Metabolic alkalosis;
Respiratory alkalosis
Allergic alveolitis see Hypersensitivity
pneumonitis
113

Alkaline phosphatase test

KEY TERMS

Allergic bronchopulmonary aspergillosis

I Allergic
bronchopulmonary
aspergillosis
Definition
Allergic bronchopulmonary aspergillosis, or
ABPA, is one of four major types of infections in
humans caused by Aspergillus fungi. ABPA is a hypersensitivity reaction that occurs in asthma patients who
are allergic to this specific fungus.

Description
ABPA is an allergic reaction to a species of
Aspergillus called Aspergillus fumigatus. It is sometimes grouped together with other lung disorders
characterized by eosinophilia–an abnormal increase
of a certain type of white blood cell in the blood–
under the heading of eosinophilic pneumonia. These
disorders are also called hypersensitivity lung
diseases.
ABPA appears to be increasing in frequency in the
United States, although the reasons for the increase
are not clear. The disorder is most likely to occur in
adult asthmatics aged 20-40. It affects males and
females equally.

Causes and symptoms
ABPA develops when the patient breathes air
containing Aspergillus spores. These spores are
found worldwide, especially around riverbanks,
marshes, bogs, forests, and wherever there is wet or
decaying vegetation. They are also found on wet
paint, construction materials, and in air conditioning systems. ABPA is a nosocomial infection,
which means that a patient can get it in a hospital.
When Aspergillus spores reach the bronchi, which
are the branches of the windpipe that lead into the
lungs, the bronchi react by contracting spasmodically. So the patient has difficulty breathing and
usually wheezes or coughs. Many patients with
ABPA also run a low-grade fever and lose their
appetites.
Complications
Patients with ABPA sometimes cough up large
amounts of blood, a condition that is called hemoptysis. They may also develop a serious long-term form of
bronchiectasis, the formation of fibrous tissue in the
lungs. Bronchiectasis is a chronic bronchial disorder
caused by repeated inflammation of the airway, and

114

KEY TERMS
Antifungal—A medicine used to treat infections
caused by a fungus.
Antigen—A substance that stimulates the production of antibodies.
Bronchiectasis—A disorder of the bronchial tubes
marked by abnormal stretching, enlargement, or
destruction of the walls. Bronchiectasis is usually
caused by recurrent inflammation of the airway
and is a diagnostic criterion of ABPA.
Bronchodilator— A medicine used to open up the
bronchial tubes (air passages) of the lungs.
Eosinophil—A type of white blood cell containing
granules that can be stained by eosin (a chemical
that produces a red stain).
Eosinophilia—An abnormal increase in the number
of eosinophils in the blood.
Hemoptysis—The coughing up of large amounts of
blood. Hemoptysis can occur as a complication of
ABPA.
Hypersensitivity—An excessive response by the
body to a foreign substance.
Immunoglobulin E (IgE)—A type of protein in
blood plasma that acts as an antibody to activate
allergic reactions. About 50% of patients with allergic disorders have increased IgE levels in their
blood serum.
Nosocomial infection—An infection that can be
acquired in a hospital. ABPA is a nosocomial
infection.
Precipitin—An antibody in blood that combines
with an antigen to form a solid that separates from
the rest of the blood.
Spirometer—An instrument used to test a patient’s
lung capacity.
‘‘Wheal and flare’’ reaction—A rapid response to a
skin allergy test characterized by the development
of a red, itching spot in the area where the allergen
was injected.
Wheezing—A whistling or musical sound caused
by tightening of the air passages inside the patient’s
chest.

marked by the abnormal enlargement of, or damage
to, the bronchial walls. ABPA sometimes occurs as a
complication of cystic fibrosis.

GALE ENCYCLOPEDIA OF MEDICINE

The diagnosis of ABPA is based on a combination
of the patient’s history and the results of blood tests,
sputum tests, skin tests, and diagnostic imaging. The
doctor will be concerned to distinguish between ABPA
and a worsening of the patient’s asthma, cystic fibrosis, or
other lung disorders. There are seven major criteria for
a diagnosis of allergic bronchopulmonary aspergillosis:


a history of asthma.



an accumulation of fluid in the lung that is visible on
a chest x ray.



bronchiectasis (abnormal stretching, enlarging, or
destruction of the walls of the bronchial tubes).



skin reaction to Aspergillus antigen.



eosinophilia in the patient’s blood and sputum.



Aspergillus precipitins in the patient’s blood.
Precipitins are antibodies that react with the antigen
to form a solid that separates from the rest of the
solution in the test tube.



a high level of IgE in the patient’s blood. IgE refers to
a class of antibodies in blood plasma that activate
allergic reactions to foreign particles.

Other criteria that may be used to support the
diagnosis include the presence of Aspergillus in samples of the patient’s sputum, the coughing up of plugs
of brown mucus, or a late skin reaction to the
Aspergillus antigen.
Laboratory tests
The laboratory tests that are done to obtain this
information include a complete blood count (CBC), a
sputum culture, a blood serum test of IgE levels, and
a skin test for the Aspergillus antigen. In the skin test, a
small amount of antigen is injected into the upper
layer of skin on the patient’s forearm about four
inches below the elbow. If the patient has a high
level of IgE antibodies in the tissue, he or she will
develop what is called a ‘‘wheal and flare’’ reaction
in about 15-20 minutes. A ‘‘wheal and flare’’ reaction
is characterized by the eruption of a reddened, itching
spot on the skin. Some patients with ABPA will
develop the so-called late reaction to the skin test, in
which a red, sore, swollen area develops about six to
eight hours after the initial reaction.
Diagnostic imaging
Chest x rays and CT scans are used to check for
the presence of fluid accumulation in the lungs and
signs of bronchiectasis.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
ABPA is usually treated with prednisone
(Meticorten) or other corticosteroids taken by mouth,
and with bronchodilators.
Antifungal drugs are not used to treat ABPA
because it is caused by an allergic reaction to
Aspergillus rather than by direct infection of tissue.
Follow-up care
Patients with ABPA should be given periodic checkups with chest x rays and a spirometer test. A spirometer is
an instrument that evaluates the patient’s lung capacity.

Prognosis
Most patients with ABPA respond well to corticosteroid treatment. Others have a chronic course with
gradual improvement over time. The best indicator of
a good prognosis is a long-term fall in the patient’s IgE
level. Patients with lung complications from ABPA
may develop severe airway obstruction.

Prevention
ABPA is difficult to prevent because Aspergillus is
a common fungus; it can be found in the saliva and
sputum of most healthy individuals. Patients with
ABPA can protect themselves somewhat by avoiding
haystacks, compost piles, bogs, marshes, and other
locations with wet or rotting vegetation; by avoiding
construction sites or newly painted surfaces; and by
having their air conditioners cleaned regularly. Some
patients may be helped by air filtration systems for
their bedrooms or offices.
Resources
BOOKS

Stauffer, John L. ‘‘Lung.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange,1997.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
National Institute of Allergy and Infectious Disease.
Building 31, Room 7A-50, 31 Center Drive MSC 2520,
Bethesda, MD 20892-2520. (301) 496-5717. <http://
www.niaid.nih.gov/default.htm>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Rebecca J. Frey, PhD
115

Allergic bronchopulmonary aspergillosis

Diagnosis

Allergic purpura

I Allergic purpura
Definition
Allergic purpura (AP) is an allergic reaction of
unknown origin causing red patches on the skin and
other symptoms. AP is also called Henoch-Schonlein
purpura, named after the two doctors who first
described it.

Description
‘‘Purpura’’ is a bleeding disorder that occurs when
capillaries rupture, allowing small amounts of blood
to accumulate in the surrounding tissues. In AP, this
occurs because the capillaries are blocked by protein
complexes formed during an abnormal immune reaction. The skin is the most obvious site of reaction, but
the joints, gastrointestinal tract, and kidneys are also
often affected.
AP affects approximately 35,000 people in the
United States each year. Most cases are children
between the ages of two and seven. Boys are affected
more often than girls, and most cases occur from late
fall to winter.

Causes and symptoms
Causes
AP is caused by a reaction involving antibodies,
special proteins of the immune system. Antibodies are
designed to bind with foreign proteins, called antigens.
In some situations, antigen-antibody complexes can
become too large to remain suspended in the bloodstream. When this occurs, they precipitate out and
become lodged in the capillaries. This can cause the
capillary to burst, allowing a local hemorrhage.
The source of the antigen causing AP is unknown.
Antigens may be introduced by bacterial or viral
infection. More than 75% of patients report having had
an infection of the throat, upper respiratory tract, or
gastrointestinal system several weeks before the onset
of AP. Other complex molecules can act as antigens
as well, including drugs such as antibiotics or vaccines.
Otherwise harmless substances that stimulate an immune
reaction are known as allergens. Drug allergens that may
cause AP include penicillin, ampicillin, erythromycin,
and quinine. Vaccines possibly linked to AP include
those for typhoid, measles, cholera, and yellow fever.
Symptoms
The onset of AP may be preceded by a headache,
fever, and loss of appetite. Most patients first develop
116

KEY TERMS
Glomeruli—Knots of capillaries in the kidneys
responsible for filtering the blood (singular,
glomerulus).
an itchy skin rash. The rash is red, either flat or raised,
and may be small and freckle-like. The rash may also
be larger, resembling a bruise. Rashes become purple
and then rust colored over the course of a day, and
fade after several weeks. Rashes are most common on
the buttocks, abdomen, and lower extremities. Rashes
higher on the body may also occur, especially in
younger children.
Joint pain and swelling is common, especially
in the knees and ankles. Abdominal pain occurs in
almost all patients, along with blood in the body
waste (feces). About half of all patients show blood
in the urine, low urine volume, or other signs of kidney
involvement. Kidney failure may occur due to widespread obstruction of the capillaries in the filtering
structures called glomeruli. Kidney failure develops
in about 5% of all patients, and in 15% of those with
elevated blood or protein in the urine.
Less common symptoms include prolonged headache, fever, and pain and swelling of the scrotum.
Involvement of other organ systems may lead to
heart attack (myocardial infarction), inflammation of
the pancreas (pancreatitis), intestinal obstruction, or
bowel perforation.

Diagnosis
Diagnosis of AP is based on the symptoms and
their development, a careful medical history, and
blood and urine tests. X rays or computed tomography scans (CT) may be performed to assess complications in the bowel or other internal organs.

Treatment
Most cases of AP resolve completely without
treatment. Nonetheless, a hospital stay is required
because of the possibility of serious complications.
Non-aspirin pain relievers may be given for joint
pain. Corticosteroids (like prednisone) are sometimes
used, although not all specialists agree on their utility.
Kidney involvement requires monitoring and correction of blood fluids and electrolytes.
Patients with severe kidney complications may
require a kidney biopsy so that tissue can be analyzed.
Even after all other symptoms subside, elevated levels
GALE ENCYCLOPEDIA OF MEDICINE

Allergic rhinitis

of blood or protein in the urine may persist for months
and require regular monitoring. Hypertension or kidney failure may develop months or even years after the
acute phase of the disease. Kidney failure requires
dialysis or transplantation.

Prognosis
Most people who develop AP become better on
their own after several weeks. About half of all
patients have at least one recurrence. Cases that do
not have kidney complications usually have the best
prognosis.
Resources
PERIODICALS

Andreoli, S. P. ‘‘Chronic Glomerulonephritis in
Childhood. Membranoproliferative
Glomerulonephritis, Henoch-Schonlein
PurpuraNnephritis, and IgA Nephropathy.’’ Pediatric
Clinics of North America 42, no. 6 (December 1995):
1487-1503.
OTHER

‘‘Henoch-Schonlein Purpura.’’ Vanderbilt University
Medical Center. <http://www.mc.vanderbilt.edu/
peds/pidl/nephro/henoch.html>.

Richard Robinson

Allergic rhinitis

This illustration depicts excessive mucus production in the
nose after inhalation of airborne pollen. (Photo Researchers,
Inc. Reproduced by permission.)

Definition
Allergic rhinitis, more commonly referred to as
hay fever, is an inflammation of the nasal passages
caused by allergic reaction to airborne substances.

Description
Allergic rhinitis (AR) is the most common allergic
condition and one of the most common of all minor
afflictions. It affects between 10-20% of all people in the
United States, and is responsible for 2.5% of all doctor
visits. Antihistamines and other drugs used to treat allergic rhinitis make up a significant fraction of both
prescription and over-the-counter drug sales each year.
There are two types of allergic rhinitis: seasonal
and perennial. Seasonal AR occurs in the spring, summer, and early fall, when airborne plant pollens are at
their highest levels. In fact, the term hay fever is really
a misnomer, since allergy to grass pollen is only one
cause of symptoms for most people. Perennial AR
GALE ENCYCLOPEDIA OF MEDICINE

occurs all year and is usually caused by home or workplace airborne pollutants. A person can be affected
by one or both types. Symptoms of seasonal AR are
worst after being outdoors, while symptoms of perennial AR are worst after spending time indoors.
Both types of allergies can develop at any age,
although onset in childhood through early adulthood
is most common. Although allergy to a particular
substance is not inherited, increased allergic sensitivity
may ‘‘run in the family.’’ While allergies can improve
on their own over time, they can also become worse
over time.

Causes and symptoms
Causes
Allergic rhinitis is a type of immune reaction.
Normally, the immune system responds to foreign
117

Allergic rhinitis

KEY TERMS
Allergen—A substance that provokes an allergic
response.
Anaphylaxis—Increased sensitivity caused by previous exposure to an allergen1 that can result in
blood vessel dilation (swelling) and smooth muscle
contraction. Anaphylaxis can result in sharp blood
pressure drops and difficulty breathing.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Antigen—A foreign protein to which the body
reacts by making antibodies.
Granules—Small packets of reactive chemicals
stored within cells.
Histamine—A chemical released by mast cells that
activates pain receptors and causes cells to become
leaky.
Mast cells—A type of immune system cell that is
found in the lining of the nasal passages and eyelids, displays a type of antibody called immunoglobulin type E (IgE) on its cell surface, and participates
in the allergic response by releasing histamine from
intracellular granules.

microorganisms, or particles, like pollen or dust, by
producing specific proteins, called antibodies, that are
capable of binding to identifying molecules, or antigens,
on the foreign particle. This reaction between antibody
and antigen sets off a series of reactions designed to
protect the body from infection. Sometimes, this same
series of reactions is triggered by harmless, everyday
substances. This is the condition known as allergy,
and the offending substance is called an allergen.
Like all allergic reactions, AR involves a special
set of cells in the immune system known as mast cells.
Mast cells, found in the lining of the nasal passages
and eyelids, display a special type of antibody, called
immunoglobulin type E (IgE), on their surface. Inside,
mast cells store reactive chemicals in small packets,
called granules. When the antibodies encounter
allergens, they trigger release of the granules, which
spill out their chemicals onto neighboring cells, including blood vessels and nerve cells. One of these
chemicals, histamine, binds to the surfaces of these
other cells, through special proteins called histamine
receptors. Interaction of histamine with receptors on
blood vessels causes neighboring cells to become
leaky, leading to the fluid collection, swelling, and
118

increased redness characteristic of a runny nose and
red, irritated eyes. Histamine also stimulates pain
receptors, causing the itchy, scratchy nose, eyes, and
throat common in allergic rhinitis.
The number of possible airborne allergens is
enormous. Seasonal AR is most commonly caused
by grass and tree pollens, since their pollen is produced
in large amounts and is dispersed by the wind. Showy
flowers, like roses or lilacs, that attract insects produce
a sticky pollen that is less likely to become airborne.
Different plants release their pollen at different times
of the year, so seasonal AR sufferers may be most
affected in spring, summer, or fall, depending on
which plants provoke a response. The amount of pollen
in the air is reflected in the pollen count, often broadcast on the daily news during allergy season. Pollen
counts tend to be lower after a good rain that washes
the pollen out of the air and higher on warm, dry,
windy days.
Virtually any type of tree or grass may cause AR.
A few types of weeds that tend to cause the most
trouble for people include the following:


ragweed



sagebrush



lamb’s-quarters



plantain



pigweed



dock/sorrel



tumbleweed

Perennial AR is often triggered by house dust, a
complicated mixture of airborne particles, many of
which are potent allergens. House dust contains
some or all of the following:


house mite body parts. All houses contain large numbers of microscopic insects called house mites. These
harmless insects feed on fibers, fur, and skin shed by
the house’s larger occupants. Their tiny body parts
easily become airborne.



animal dander. Animals constantly shed fur, skin
flakes, and dried saliva. Carried in the air, or transferred from pet to owner by direct contact, dander
can cause allergy in many sensitive people.



mold spores. Molds live in damp spots throughout
the house, including basements, bathrooms, air
ducts, air conditioners, refrigerator drains, damp
windowsills, mattresses, and stuffed furniture.
Mildew and other molds release airborne spores
that circulate throughout the house.
GALE ENCYCLOPEDIA OF MEDICINE



cigarette smoke



perfume



cosmetics



cleansers



copier chemicals



industrial chemicals



construction material gases
Symptoms

Inflammation of the nose, or rhinitis, is the
major symptom of AR. Inflammation causes itching,
sneezing, runny nose, redness, and tenderness. Sinus
swelling can constrict the eustachian tube that connects the inner ear to the throat, causing a congested
feeling and ‘‘ear popping.’’ The drip of mucus from the
sinuses down the back of the throat, combined with
increased sensitivity, can also lead to throat irritation
and redness. AR usually also causes redness, itching,
and watery eyes. Fatigue and headache are also
common.

Diagnosis
Diagnosing seasonal AR is usually easy and can
often be done without a medical specialist. When
symptoms appear in spring or summer and disappear
with the onset of cold weather, seasonal AR is almost
certainly the culprit. Other causes of rhinitis, including infection, can usually be ruled out by a physical
examination and a nasal smear, in which a sample of
mucus is taken on a swab for examination.
Allergy tests, including skin testing and provocation testing, can help identify the precise culprit,
but may not be done unless a single source is
suspected and subsequent avoidance is possible.
Skin testing involves placing a small amount of
liquid containing a specific allergen on the skin and
then either poking, scratching, or injecting it into
the skin surface to observe whether redness and
swellings occurs. Provocation testing involves challenging an individual with either a small amount of
an inhalable or ingestable allergen to see if a response
is elicited.
Perennial AR can also usually be diagnosed by
careful questioning about the timing of exposure
and the onset of symptoms. Specific allergens can be
identified through allergy skin testing.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Avoidance of the allergens is the best treatment,
but this is often not possible. When it is not possible to
avoid one or more allergens, there are two major forms
of medical treatment, drugs and immunotherapy.
Drugs
ANTIHISTAMINES. Antihistamines block the histamine receptors on nasal tissue, decreasing the effect of
histamine release by mast cells. They may be used after
symptoms appear, though they may be even more
effective when used preventively, before symptoms
appear. A wide variety of antihistamines are available.

Older antihistamines often produce drowsiness as
a major side effect. Such antihistamines include the
following:


diphenhydramine (Benadryl and generics)



chlorpheniramine (Chlor-trimeton and generics)



brompheniramine (Dimetane and generics)



clemastine (Tavist and generics).

Newer antihistamines that do not cause drowsiness are available by prescription and include the
following:


astemizole (Hismanal)



fexofenadine (Allegra)



cetirizine (Zyrtec)



azelastin HCl (Astelin).

Loratidine (Claritin) was available only by prescription but was released to over-the-counter status
by the FDA.
Hismanal has the potential to cause serious heart
arrhythmias when taken with the antibiotic erythromycin, the antifungal drugs ketoconazole and itraconazole, or the antimalarial drug quinine. Taking more than
the recommended dose of Hismanal can also cause
arrhythimas. Seldane (terfenadine), the original nondrowsy antihistamine, was voluntarily withdrawn from
the market by its manufacturers in early 1998 because
of this potential and because of the availability of an
equally effective, safer alternative drug, fexofenadine.
LEUKOTRIENE RECEPTOR ANTAGONISTS. Leukotriene receptor antagonists (montelukast or Singulair
and zafirlukast or Accolate) are a newer class of drugs
used daily to help prevent asthma. They’ve also become
approved in the United States to treat allergic rhinitis.
DECONGESTANTS. Decongestants constrict blood
vessels to counteract the effects of histamine. This
decreases the amount of blood in the nasopahryngeal

119

Allergic rhinitis

Other potential causes of perennial allergic rhinitis include the following:

Allergic rhinitis

and sinus mucosa and reduces swelling. Nasal sprays
are available that can be applied directly to the nasal
lining and oral systemic preparations are available.
Decongestants are stimulants and may cause increased
heart rate and blood pressure, headaches, isomnia,
agitation and difficulty emptying the bladder. Use of
topical decongestants for longer than several days can
cause loss of effectiveness and rebound congestion, in
which nasal passages become more severely swollen
than before treatment.

symptom relief, western herbal remedies including eyebright (Euphrasia officinalis) and nettle (Urtica dioica) may
be helpful. Bee pollen may also be effective in alleviating
or eliminating AR symptoms. A 2004 report said that
phototherapy (treatment with a combination of ultraviolet and visible light) decreased the symptoms of allergic
rhinitis in a majority of patients who did not respond well
to traditional drug treatment.

TOPICAL CORTICOSTEROIDS. Topical corticosteroids reduce mucous membrane inflammation and are
available by prescription. Allergies tend to become
worse as the season progresses because the immune
system becomes sensitized to particular antigens and
can produce a faster, stronger response. Topical
corticosteroids are especially effective at reducing this
seasonal sensitization because they work more slowly
and last longer than most other medication types. As
a result, they are best started before allergy season
begins. Side effects are usually mild, but may include
headaches, nosebleeds, and unpleasant taste sensations.

Most people with AR can achieve adequate relief
with a combination of preventive strategies and treatment. While allergies may improve over time, they
may also get worse or expand to include new allergens.
Early treatment can help prevent an increased sensitization to other allergens.

Prognosis

Prevention
Reducing exposure to pollen may improve symptoms of seasonal AR. Strategies include the following:


stay indoors with windows closed during the morning hours, when pollen levels are highest



keep car windows up while driving



use a surgical face mask when outside



avoid uncut fields



learn which trees are producing pollen in which seasons, and avoid forests at the height of pollen season



wash clothes and hair after being outside



clean air conditioner filters in the home regularly



use electrostatic filters for central air conditioning

MAST CELL STABILIZERS. Cromolyn sodium pre-

vents the release of mast cell granules, thereby preventing release of histamine and the other chemicals
contained in them. It acts as a preventive treatment if it
is begun several weeks before the onset of the allergy
season. It can be used for perennial AR as well.
Immunotherapy
Immunotherapy, also known as desensitization or
allergy shots, alters the balance of antibody types in the
body, thereby reducing the ability of IgE to cause allergic
reactions. Immunotherapy is preceded by allergy testing
to determine the precise allergens responsible. Injections
involve very small but gradually increasing amounts of
allergen, over several weeks or months, with periodic
boosters. Full benefits may take up to several years to
achieve and are not seen at all in about one in five
patients. Individuals receiving all shots will be monitored closely following each shot because of the small
risk of anaphylaxis, a condition that can result in difficulty breathing and a sharp drop in blood pressure.

Alternative treatment
Alternative treatments for AR often focus on modulation of the body’s immune response, and
frequently center around diet and lifestyle adjustments.
Chinese herbal medicine can help rebalance a person’s
system, as can both acute and constitutional homeopathic treatment. Vitamin C in substantial amounts can
help stabilize the mucous membrane response. For
120

Moving to a region with lower pollen levels is
rarely effective, since new allergies often develop
Preventing perennial AR requires identification of
the responsible allergens.
Mold spores:


keep the house dry through ventilation and use of
dehumidifiers



use a disinfectant such as dilute bleach to clean
surfaces such as bathroom floors and walls



have ducts cleaned and disinfected



clean and disinfect air conditioners and coolers



throw out moldy or mildewed books, shoes, pillows,
or furniture
House dust:



vacuum frequently, and change the bag regularly. Use
a bag with small pores to catch extra-fine particles
GALE ENCYCLOPEDIA OF MEDICINE

clean floors and walls with a damp mop



install electrostatic filters in heating and cooling
ducts, and change all filters regularly
Animal dander:



avoid contact if possible



wash hands after contact



vacuum frequently



keep pets out of the bedroom, and off furniture, rugs,
and other dander-catching surfaces



have your pets bathed and groomed frequently

Resources
PERIODICALS

Finn, Robert. ‘‘Rhinoohototherapy Targets Allergic
Rhinitis.’’ Skin & Allergy News (July 2004): 62.
‘‘What’s New in: Asthma and Allergic Rhinitis.’’ Pulse
(September 20, 2004): 50.

Richard Robinson
Teresa G. Odle

I Allergies
Definition
Allergies are abnormal reactions of the immune
system that occur in response to otherwise harmless
substances.

Description
Allergies are among the most common of medical
disorders. It is estimated that 60 million Americans, or
more than one in every five people, suffer from some
form of allergy, with similar proportions throughout
much of the rest of the world. Allergy is the single
largest reason for school absence and is a major source
of lost productivity in the workplace.
An allergy is a type of immune reaction. Normally,
the immune system responds to foreign microorganisms or particles by producing specific proteins called
antibodies. These antibodies are capable of binding
to identifying molecules, or antigens, on the foreign
particle. This reaction between antibody and antigen
sets off a series of chemical reactions designed to protect the body from infection. Sometimes, this same
series of reactions is triggered by harmless, everyday
substances such as pollen, dust, and animal danders.
GALE ENCYCLOPEDIA OF MEDICINE

When this occurs, an allergy develops against the
offending substance (an allergen.)
Mast cells, one of the major players in allergic
reactions, capture and display a particular type of
antibody, called immunoglobulin type E (IgE) that
binds to allergens. Inside mast cells are small chemical-filled packets called granules. Granules contain a
variety of potent chemicals, including histamine.
Immunologists separate allergic reactions into
two main types: immediate hypersensitivity reactions,
which are predominantly mast cell-mediated and
occur within minutes of contact with allergen; and
delayed hypersensitivity reactions, mediated by
T cells (a type of white blood cells) and occurring
hours to days after exposure.
Inhaled or ingested allergens usually cause
immediate hypersensitivity reactions. Allergens bind
to IgE antibodies on the surface of mast cells, which
spill the contents of their granules out onto neighboring cells, including blood vessels and nerve cells.
Histamine binds to the surfaces of these other cells
through special proteins called histamine receptors.
Interaction of histamine with receptors on blood vessels causes increased leakiness, leading to the fluid
collection, swelling and increased redness. Histamine
also stimulates pain receptors, making tissue more
sensitive and irritable. Symptoms last from one to
several hours following contact.
In the upper airways and eyes, immediate hypersensitivity reactions cause the runny nose and itchy,
bloodshot eyes typical of allergic rhinitis. In the gastrointestinal tract, these reactions lead to swelling and
irritation of the intestinal lining, which causes the
cramping and diarrhea typical of food allergy.
Allergens that enter the circulation may cause hives,
angioedema, anaphylaxis, or atopic dermatitis.
Allergens on the skin usually cause delayed hypersensitivity reaction. Roving T cells contact the allergen, setting in motion a more prolonged immune
response. This type of allergic response may develop
over several days following contact with the allergen,
and symptoms may persist for a week or more.

Causes and symptoms
Allergens enter the body through four main
routes: the airways, the skin, the gastrointestinal
tract, and the circulatory system.


Airborne allergens cause the sneezing, runny nose,
and itchy, bloodshot eyes of hay fever (allergic rhinitis). Airborne allergens can also affect the lining of
the lungs, causing asthma, or conjunctivitis (pink
121

Allergies



Allergies

Allergic rhinitis is commonly triggered by
exposure to household dust, animal fur,
or pollen. The foreign substance that
triggers an allergic reaction is called
an allergen.

Pollen grains

The presence of an allergen causes the
body's lymphocytes to begin producing
IgE antibodies. The lymphocytes of an
allergy sufferer produce an unusually
large amount of IgE.

Lymphocyte

FIRST EXPOSURE
IgE
Histamine

IgE molecules attach to mast
cells, which contain histamine.

The allergic response. (Illustration by Hans & Cassady.)

In a future exposure to the same substance,
the antibodies on the mast cells bind to the
allergens, and the cells release their histamine.

SECOND EXPOSURE

Histamine travels to receptor sites in the nasal
passages. When histamine molecules enter the
sites they trigger dilation of the blood vessels,
swelling, irritation, and increased production
of mucus.
Antihistamines

D

Antihistamine drugs block histamine molecules
from entering receptor sites, thus preventing or
reducing swelling, congestion and irritation.

Second and subsequent exposure to allergen. (Illustration by Hans & Cassady.)

122

GALE ENCYCLOPEDIA OF MEDICINE

Allergen—A substance that provokes an allergic
response.
Allergic rhinitis—Inflammation of the mucous membranes of the nose and eyes in response to an
allergen.
Anaphylaxis—Increased sensitivity caused by previous exposure to an allergen that can result in
blood vessel dilation and smooth muscle contraction. Anaphylaxis can result in sharp blood pressure
drops and difficulty breathing.
Angioedema—Severe non-inflammatory swelling of
the skin, organs, and brain that can also be accompanied by fever and muscle pain.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.



Delayed hypersensitivity reactions—Allergic reactions mediated by T cells that occur hours to days
after exposure.
Granules—Small packets of reactive chemicals
stored within cells.
Histamine—A chemical released by mast cells that
activates pain receptors and causes cells to become
leaky.

Asthma—A lung condition in which the airways
become narrow due to smooth muscle contraction,
causing wheezing, coughing, and shortness of
breath.
Atopic dermatitis—Infection of the skin as a result of
exposure to airborne or food allergens.

Immune hypersensitivity reaction—Allergic reactions that are mediated by mast cells and occur
within minutes of allergen contact.
Mast cells—A type of immune system cell that is
found in the lining of the nasal passages and eyelids,
displays a type of antibody called immunoglobulin
type E (IgE) on its cell surface, and participates in the
allergic response by releasing histamine from intracellular granules.
T cells—Immune system cells or more specifically,
white blood cells, that stimulate cells to create and
release antibodies.

eye). Exposure to cockroach allergens has been associated with the development of asthma. Airborne
allergens from household pets are another common
source of environmental exposure.

Dermatitis may arise from an allergic response (such
as from poison ivy), or exposure to an irritant causing nonimmune damage to skin cells (such as soap,
cold, and chemical agents).

Antigen—A foreign protein to which the body reacts
by making antibodies.



Conjunctivitis—Inflammation of the thin lining of
the eye called the conjunctiva.
Contact dermatitis—Inflammation of the skin as a
result of contact with a substance.

Allergens in food can cause itching and swelling of
the lips and throat, cramps, and diarrhea. When
absorbed into the bloodstream, they may cause
hives (urticaria) or more severe reactions involving
recurrent, non-inflammatory swelling of the skin,
mucous membranes, organs, and brain (angioedema). Some food allergens may cause anaphylaxis,
a potentially life-threatening condition marked by
tissue swelling, airway constriction, and drop in
blood pressure. Allergies to foods such as cow’s
milk, eggs, nuts, fish, and legumes (peanuts and soybeans) are common. Allergies to fruits and vegetables may also occur.
In contact with the skin, allergens can cause reddening, itching, and blistering, called contact dermatitis.
Skin reactions can also occur from allergens introduced through the airways or gastrointestinal tract.
This type of reaction is known as atopic dermatitis.

GALE ENCYCLOPEDIA OF MEDICINE



Injection of allergens, from insect bites and stings or
drug administration, can introduce allergens directly
into the circulation, where they may cause systemwide responses (including anaphylaxis), as well as
the local ones of swelling and irritation at the injection site.

People with allergies are not equally sensitive to
all allergens. Some may have severe allergic rhinitis
but no food allergies, for instance, or be extremely
sensitive to nuts but not to any other food. Allergies
may get worse over time. For example, childhood ragweed allergy may progress to year-round dust and
pollen allergy. On the other hand, a person may lose
allergic sensitivity. Infant or childhood atopic dermatitis disappears in almost all people. More commonly,
what seems to be loss of sensitivity is instead a reduced
exposure to allergens or an increased tolerance for the
same level of symptoms.
123

Allergies

KEY TERMS

Allergies

While allergy to specific allergens is not inherited, the
likelihood of developing some type of allergy seems to be,
at least for many people. If neither parent has allergies,
the chances of a child developing allergy is approximately
10-20%; if one parent has allergies, it is 30-50%; and if
both have allergies, it is 40-75%. One source of this
genetic predisposition is in the ability to produce higher
levels of IgE in response to allergens. Those who produce
more IgE will develop a stronger allergic sensitivity.
COMMON ALLERGENS. The most common airborne allergens are the following:


plant pollens



animal fur and dander



body parts from house mites (microscopic creatures
found in all houses)



house dust



mold spores



cigarette smoke



solvents



cleaners
Common food allergens include the following:

The following types of drugs commonly cause
allergic reactions:


penicillin or other antibiotics



flu vaccines



tetanus toxoid vaccine



gamma globulin

Common causes of contact dermatitis include the
following:


poison ivy, oak, and sumac



nickel or nickel alloys



latex

Insects and other arthropods whose bites or stings
typically cause allergy include the following:


bees, wasps, and hornets



mosquitoes



fleas



scabies

Symptoms depend on the specific type of allergic
reaction. Allergic rhinitis is characterized by an itchy,
runny nose, often with a scratchy or irritated throat
due to post-nasal drip. Inflammation of the thin membrane covering the eye (allergic conjunctivitis) causes
redness, irritation, and increased tearing in the eyes.
Asthma causes wheezing, coughing, and shortness of
124

breath. Symptoms of food allergies depend on the
tissues most sensitive to the allergen and whether the
allergen was spread systemically by the circulatory
system. Gastrointestinal symptoms may include swelling and tingling in the lips, tongue, palate or throat;
nausea; cramping; diarrhea; and gas. Contact dermatitis is marked by reddened, itchy, weepy skin blisters,
and an eczema that is slow to heal. It sometimes has a
characteritic man-made pattern, such as a glove
allergy with clear demarkation on the hands, wrist,
and arms where the gloves are worn, or on the earlobes
by wearing earrings.
Whole body or systemic reactions may occur from
any type of allergen, but are more common following
ingestion or injection of an allergen. Skin reactions
include the raised, reddened, and itchy patches called
hives that characteristically blanch with pressure and
resolve within twenty-four hours. A deeper and more
extensive skin reaction, involving more extensive fluid
collection and pain, is called angioedema. This usually
occurs on the extremities, fingers, toes, and parts of the
head, neck, and face. Anaphylaxis is marked by airway
constriction, blood pressure drop, widespread tissue
swelling, heart rhythm abnormalities, and in some
cases, loss of consciousness. Other syptoms may
include, dizziness, weakness, seizures, coughing, flushing, or cramping. The symptoms may begin within five
minutes after exposure to the allergen up to one hour
or more later. Mast cells in the tissues and basophils in
the blood release mediators that give rise to the clinical
symptoms of this IgE-mediated hypersensitivity reaction. Commonly, this is associated with allergies to
medications, foods, and insect venoms. In some individuals, anaphylaxis can occur with exercise, plasma
exchange, hemodialysis, reaction to insulin, contrast
media used in certain types of medical tests, and rarely
during the administration of local anesthetics.

Diagnosis
Allergies can often be diagnosed by a careful medical history, matching the onset of symptoms to the
exposure to possible allergens. Allergy is suspected if
the symptoms presented are characteristic of an allergic reaction and this occurs repeatedly upon exposure
to the suspected allergen. Allergy tests can be used to
identify potential allergens, but these must be supported by eveidence of allergic responses in the
patient’s clinical history.
Skin tests
Skin tests are performed by administering a tiny
dose of the suspected allergen by pricking, scratching,
GALE ENCYCLOPEDIA OF MEDICINE

Allergen-Specific IgE Measurement
Tests that measure allergen-specific IgE antibodies generally follow a basic method. The allergen is
bound to a solid support, either in the form of a
cellulose sponge, microtiter plate, or paper disk. The
patient’s serum is prepared from a blood sample and is
incubated with the solid phase. If allergen specific IgE
antibodies are present, they will bind to the solid phase
and be retained there when the rest of the serum is
washed away. Next, an labeled antibody against the
IgE is added and will bind to any IgE on the solid
phase. The excess is washed away and the levels of IgE
are determined. The commonly used RAST test (radio
allergo sorbent test) employed radio-labeled Anti-IgE
antibodies. Updated methods now incorporate the use
of enyzme-labeled antibodies in ELISA assays
(enzyme-linked immunosorbent assays).
Total Serum IgE
The total level of IgE in the serum is commonly
measured with a two-site immunometric assay. Some
research indicates that there is a higher level of total
serum IgE in allergic as compared to non-allergic
people. However, this may not always be the case as
there is considerable overlap between the two groups.
This test is useful for the diagnosis of allergic fungal
sinusitis and bronchopulmonary aspergillosis. Other
conditions that are not allergic in nature may give
rise to higher IgE levels such as smoking, AIDS, infection with parasites, and IgE myeloma.
Provocation tests
These tests involve the administration of allergen to
elicit an immune response. Provocation tests, most commonly done with airborne allergens, present the allergen
GALE ENCYCLOPEDIA OF MEDICINE

directly through the route normally involved. Delayed
allergic contact dermatitis diagnosis involves similar
methods by application of a skin patch with allergen
to induce an allergic skin reaction. Food allergen provocation tests require abstinence from the suspect allergen
for two weeks or more, followed by ingestion of a
measured amount of the test substance administered as
an opaque capsule along with a placebo control.
Provocation tests are not used if anaphylaxis is is a
concern due to the patient’s medical history.
Future diagnostic methods
Attempts have been made for direct measurement
of immune mediators such as histamine, eosinophil
cationic protein (ECP), and mast cell tryptase.
Another, somewhat controversial,test is electrodermal
testing or electro-acupuncture allergy testing. This test
has been used in Europe and is under investigation in
the United States, though not approved by the Food
and Drug Administration. An electric potential is
applied to the skin, the allergen presented, and the
electrical resistance observed for changes. This
method has not been verified.

Treatment
Avoiding allergens is the first line of defense to
reduce the possibility of an allergic attack. It is helpful
to avoid environmental irritants such as tobacco
smoke, perfumes, household cleaning agents, paints,
glues, air fresheners, and potpourri. Nitrogen dioxide
from poorly vented gas stoves, woodburning stoves,
and artificial fireplaces has also been linked to poor
asthma control. Dust mite control is particularly
important in the bedroom areas by use of allergenimpermeable covers on mattress and pillows, frequent
washing of bedding in hot water, and removal of items
that collect dust such as stuffed toys. Mold growth may
be reduced by lowering indoor humidity, repair of
house foundations to reduce indoor leaks and seepage,
and installing exhaust systems to ventilate areas where
steam is generated such as the bathroom or kitchen.
Allergic individuals should avoid pet allergens such as
saliva, body excretions, pelts, urine, or feces. For those
who insist on keeping a pet, restriction of the animal’s
activity to certain areas of the home may be beneficial.
Complete environmental control is often difficult
to accomplish, hence therapuetic interventions may
become necessary. A large number of prescription
and over-the-counter drugs are available for treatment
of immediate hypersensitivity reactions. Most of these
work by decreasing the ability of histamine to provoke
symptoms. Other drugs counteract the effects of
125

Allergies

puncturing or injecting the skin. The allergen is
applied to the skin as an auqeous extract, usually on
the back, forearms, or top of the thighs. Once in the
skin, the allergen may produce a classic immune wheal
and flare response (a skin lesion with a raised, white,
compressible area surrounded by a red flare). The tests
usually begin with prick tests or patch tests that expose
the skin to small amounts of allergen to observe the
response. A positive reaction will occur on the skin
even if the allergen is at levels normally encountered in
food or in the airways. Reactions are usually evaluated
approximately fifteen minutes after exposure.
Intradermal skin tests involved injection of the allergen into the dermis of the skin. These tests are more
sensitive and are used for allergies associated with risk
of death, such as allergies to antibiotics.

Allergies

histamine by stimulating other systems or reducing
immune responses in general.
Antihistamines
Antihistamines block the histamine receptors on
nasal tissue, decreasing the effect of histamine released
by mast cells. They may be used after symptoms appear,
though they may be even more effective when used
preventively, before symptoms appear. Antihistamines
help reduce sneezing, itching, and rhinorrhea. A wide
variety of antihistamines are available.
Older, first generation antihistamines often produce drowsiness as a major side effect, as well as dry
mouth, tachycardia, blurred vision, constipation, and
lower the threshold for seizures. These medications
also have similar effects to a alcohol and care should
be taken when operating motor vehicles, as individuals
may not be aware that they are impaired. Such antihistamines include the following:


diphenhydramine (Benadryl and generics)



chlorpheniramine (Chlor-trimeton and generics)



brompheniramine (Dimetane and generics)



clemastine (Tavist and generics)

Newer antihistamines that do not cause drowsiness or pass the blood-brain barrier are available by
prescription and include the following:


loratidine (Claritin)



cetirizine (Zyrtec)



fexofenadine (Allegra)

Desloratadine (Clarinex) was approved in 2004 in
syrup form for children two years and older for seasonal allergies and for hives of unknown cause in children as young as six months. It is the only nonsedating
antihistamine approved as of 2004 for children as
young as six months.
Hismanal has the potential to cause serious heart
arrhythmias when taken with the antibiotic erythromycin, the antifungal drugs ketoconazole and itraconazole,
or the antimalarial drug quinine. Taking more than the
recommended dose of Hismanal can also cause
arrhythimas. Seldane (terfenadine), the original nondrowsy antihistamine, was voluntarily withdrawn from
the market by its manufacturers in early 1998 because of
this potential and because of the availability of an
equally effective, safer alternative drug, fexofenadine.
Decongestants
Decongestants constrict blood vessels to the
mucosa to counteract the effects of histamine. This
126

decreases the amount of blood in the nasopahryngeal
and sinus mucosa and reduces swelling. Nasal sprays
are available that can be applied directly to the nasal
lining and oral systematic preparations are available.
Decongestants are stimulants and may cause increased
heart rate and blood pressure, headaches, insomnia,
agitation, and difficulty emptying the bladder. Use of
topical decongestants for longer than several days can
cause loss of effectiveness and rebound congestion,
in which nasal passages become more severely swollen
than before treatment.
Topical corticosteroids
Topical corticosteroids reduce mucous membrane
inflammation by decreasing the amount of fluid moved
from the vascular spaces into the tissues. These medications reduce the recruitment of inflammatory cells as
well as the synthesis of cytokines. They are available by
prescription. Allergies tend to become worse as the
season progresses because the immune system becomes
sensitized to particular antigens and can produce a
faster, stronger response. Topical corticosteroids are
especially effective at reducing this seasonal sensitization because they work more slowly and last longer
than most other medication types. As a result, they
are best started before allergy season begins. Side
effects are usually mild, but may include headaches,
nosebleeds, and unpleasant taste sensations.
Bronchodilators or metered-dose inhalers (MDI)
Because allergic reactions involving the lungs
cause the airways or bronchial tubes to narrow, as in
asthma, bronchodilators, which cause the smooth muscle lining the airways to open or dilate, can be very
effective. When inhalers are used, it is important that
the patient be educated in the proper use of these
medications. The inhaler should be shaken, and the
patient should breathe out to expel air from the lungs.
The inhaler should be placed at least two fingerbreadths in front of the mouth. The medication should
be aimed at the back of the throat, and the inhaler
activated while breathing in quite slowly 3-4 seconds.
The breath should be held for at least ten seconds, and
then expelled. At least thirty to sixty seconds should
pass before the inhaler is used again. Care should be
taken to properly wash out the mouth and brush the
teeth following use, as residual medication remains in
this area with only a small amount actually reaching
the lungs. Some bronchodilators used to treat acute
asthma attacks include adrenaline, albuterol, Maxair,
Proventil, or other ‘‘adrenoceptor stimulants,’’ most
often administered as aerosols. Successfully managing
asthma and allergies can reduce the use of inhalers.
GALE ENCYCLOPEDIA OF MEDICINE

Anticholinergics
Ipratropium bromide (atrovent) and atropine sulfate are achticholinergic drugs used for the treatment
of asthma. Ipratropium is used for treating asthmatics
in emergency situations with a nebulizer.
Nonsteroidal drugs
MAST CELL STABILIZERS. Cromolyn sodium prevents the release of mast cell granules, thereby preventing the release of histamine and other chemicals
contained in them. It acts as a preventive treatment if it
is begun several weeks before the onset of the allergy
season. It can also be used for year round allergy
prevention. Cromolyn sodium is available as a nasal
spray for allergic rhinitis and in aerosol (a suspension
of particles in gas) form for asthma.
LEUKOTRIENE MODIFIERS. These medications are

useful for individuals with aspirin sensitivity, sinusitis,
polposis, urticaria. Examples include zafirlukast
(Accolate), montelukast (Singulair), and zileuton
(Zyflo). When zileuton is used, care must be taken to
measure liver enzymes.
Immunotherapy
In this form of therapy, allergen is injected into the
skin in increasing doses over a specific period of time.
This may be helpful for patients who do not respond to
medications or avoidance of allergens in the environment. This type of therapy may reduce the need for
medications. A 2004 study recommended that children
who have severe reactions to insect sting receive immunotherapy to protect them against future stings.
Treatment of contact dermatitis
An individual suffering from contact dermatitis
should initially take steps to avoid possible sources of
exposure to the offending agent. Calamine lotion
applied to affected skin can reduce irritation somewhat,
as can cold water compresses. Side effects of topical
agents may include over-drying of the skin. In the case
of acute contact dermatitis, short-term oral corticosteroid therapy may be appropriate. Moderately strong
coricosteroids can also be applied as a wrap for twentyfour hours. Health care workers are especially at risk
for hand eruptions due to glove use.

GALE ENCYCLOPEDIA OF MEDICINE

Treatment of anaphylaxis
The emergency condition of anaphylaxis is treated
with injection of adrenaline, also known as epinephrine. People who are prone to anaphylaxis because
of food or insect allergies often carry an ‘‘Epi-pen’’
containing adrenaline in a hypodermic needle. Other
medications may be given to aid the action of the epipen. Prompt injection can prevent a more serious
reaction from developing. Particular care should be
taken to assess the affected individual’s airway status,
and he or she should be placed in a recumbent pose
and vital signs determined. If a reaction resulted from
insect sting or an injection, a tourniquet may need
to be placed proximal to the area where the agent
penetrated the skin. This should then be released at
intervals of ten minutes at a time, for one to two
minutes duration. If the individual does not respond
to such interventions, then emergency treatment is
appropriate.

Alternative treatment
Any alternative treatment for allergies begins with
finding the cause and then helping the patient to avoid
or eliminate the allergen, although this is not always
possible. As with any alternative therapy, a physician
should be consulted before initiating a new form of
treatment. Education on the use of alternative agents
is critical, as they are still ‘‘drugs’’ even though they
are derived from natural sources. Various categories
of alternative remedies may be helpful in allergy treatment, including:


antihistamines: vitamin C and the bioflavonoid
hesperidin act as natural anithistamines.



decongestants: vitamin C, the homeopathic remedies Ferrum phosphoricum and Kali muriaticum
(used alternately), and the dietary supplement
N-acetylcysteine are believed to have decongestant effects.



mast cell stabilizers: the bioflavonoids quercetin and
hesperidin may help stabilize mast cells.



immunotherapy: the herbs echinacea (Echinacea
spp.) and astragalus or milk-vetch root (Astragalus
membranaceus) may possibly help to strengthen the
immune system.



bronchodilators: the herbal remedies ephedra
(Ephedra sinica, also known as ma huang in traditional Chinese medicine), khellin (Ammi visnaga) and
cramp bark (Viburnum opulus) are believed to help
open the airways.

127

Allergies

This is done through good communication between
the physician and patient, self-management with written action plans, avoiding allergy triggers, and
through the use of preventive medications such as
montelukast.

Allergy tests

Treatment of contact dermatitis
A variety of herbal remedies, either applied topically or taken internally, may possibly assist in the
treatment of contact dermatitis. A poultice (crushed
herbs applied directly to the affected area) made of
jewelweed (Impatiens spp.) or chickweed (Stellaria
media) may soothe the skin. A cream or wash containing calendula (Calendula officinalis), a natural antiseptic and anti-inflammatory agent, may help heal the
rash when applied topically. Homeopathic treatment
may include such remedies as Rhus toxicodendron,
Apis mellifica, or Anacardium taken internally. A
qualified homeopathic practitioner should be consulted to match the symptoms with the correct remedy.
Care should be taken with any agent taken internally.

Prognosis
Allergies can improve over time, although they
often worsen. While anaphylaxis and severe asthma
are life-threatening, other allergic reactions are not.
Learning to recognize and avoid allergy-provoking
situations allows most people with allergies to lead
normal lives.

Prevention
Avoiding allergens is the best means of limiting
allergic reactions. For food allergies, there is no effective
treatment except avoidance. By determining the allergens that are causing reactions, most people can learn to
avoid allergic reactions from food, drugs, and contact
allergens such as poison ivy or latex. The government
will help now, since passing the Food Allergen Labeling
and Consumer Protection Act in 2004. Beginning
January 1, 2006, food manufacturers will be required
to clearly state if a product contains any of the eight
major food allergens that are responsible for more than
90% of allergic reactions to foods. These are milk,
eggs, peanuts, tree nuts, fish, shellfish, wheat, and soy.
Airborne allergens are more difficult to avoid,
although keeping dust and animal dander from collecting in the house may limit exposure. Cromolyn
sodium can prevent mast cell degranulation, thereby
limiting the allergic response.
Immunotherapy, also known as desensitization or
allergy shots, alters the balance of antibody types in
the body, thereby reducing the ability of IgE to cause
allergic reactions. Immunotherapy is preceded by
allergy testing to determine the precise allergens
responsible. Injections involve very small but gradually increasing amounts of allergen, over several weeks
or months, with periodic boosters. Full benefits may
128

take up to several years to achieve and are not seen at
all in about one in five patients. Individuals receiving
all shots will be monitored closely following each shot
because of the small risk of anaphylaxis, a condition
that can result in difficulty breathing and a sharp drop
in blood pressure.
Other drugs, such as leukotriene modifiers, are
used to prevent asthma attacks and in the long-term
management of allergies and asthma.
Resources
BOOKS

Hans-Uwe, Simon, editor. CRC Desk Reference for Allergy
and Asthma. Boca Raton: CRC Press, 2000.
Kemp, Stephen F., and Richard Lockey, editors. Diagnostic
Testing of Allergic Disease. New York: Marcel Dekker,
Inc., 2000.
Lieberman, Phil, and Johh Anderson, editors. Allergic
Diseases: Diagnosis and Treatment. 2nd ed. Totowa:
Humana Press, Inc., 2000.
PERIODICALS

‘‘Children With Serious Insect-sting Allergies Should Get
Shots.’’ Drug Week (September 3, 2004): 19.
‘‘FDA Approves Clarinex Syrup for Allergies and Hives in
Children.’’ Biotech Week (September 29, 2004): 617.
‘‘President Bush Signs Bill that Will Benefit Millions With
Food Allergies.’’ Immunotherapy Weekly (September 1,
2004): 50.
‘‘What’s New in: Asthma and Allergic Rhinitis.’’ Pulse
(September 20, 2004): 50.

Richard Robinson
Jill Granger, MS
Teresa G. Odle

I Allergy tests
Definition
Allergy tests indicate a person’s allergic sensitivity
to commonly encountered environmental substances.

Purpose
Allergy is a reaction of the immune system.
Normally, the immune system responds to foreign
microorganisms and particles, like pollen or dust,
by producing specific proteins called antibodies that
are capable of binding to identifying molecules, or
antigens, on the foreign organisms. This reaction
between antibody and antigen sets off a series of
reactions designed to protect the body from infection. Sometimes, this same series of reactions is
GALE ENCYCLOPEDIA OF MEDICINE

This patient is being exposed to certain allergens as part of
an allergy test. (Custom Medical Stock Photo. Reproduced by
permission.)

triggered by harmless, everyday substances. This is
the condition known as allergy, and the offending
substance is called an allergen. Common inhaled
allergens include pollen, dust, and insect parts from
tiny house mites. Common food allergens include
nuts, fish, and milk.
Allergic reactions involve a special set of cells
in the immune system known as mast cells. Mast
cells serve as guards in the tissues where the body
meets the outside world: the skin, the mucous
membranes of the eyes and other areas, and the linings of the respiratory and digestive systems. Mast
cells display a special type of antibody, called immunoglobulin type E (IgE), on their surface. Inside,
mast cells store reactive chemicals in small packets,
called granules. When the antibodies encounter allergens, they trigger the release of granules, which spill
out their chemicals onto neighboring cells, including
blood vessels and nerve cells. One of these chemicals,
histamine, binds to the surfaces of these other cells,
through special proteins called histamine receptors.
Interaction of histamine with receptors on blood
vessels causes neighboring cells to become leaky,
leading to the fluid collection, swelling, and increased
redness characteristic of a runny nose and red, irritated eyes. Histamine also stimulates pain receptors,
causing the itchy, scratchy nose, eyes, and throat
common in allergic rhinitis.
The particular allergens to which a person is sensitive can be determined through allergy testing.
Allergy tests may be performed on the skin or using
blood serum in a test tube. During skin tests, potential
allergens are placed on the skin and the reaction
is observed. In radio-allergosorbent allergy testing
(RAST), a patient’s blood serum is combined
GALE ENCYCLOPEDIA OF MEDICINE

Allergen—A substance that provokes an allergic
response.
Anaphylaxis—Increased sensitivity caused by
previous exposure to an allergen that can result
in blood vessel dilation (swelling) and smooth
muscle contraction. Anaphylaxis can result in
sharp blood pressure drops and difficulty
breathing.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Antigen—A foreign protein to which the body
reacts by making antibodies.
Histamine—A chemical released by mast cells that
activates pain receptors and causes cells to become
leaky.
Mast cells—A type of immune system cell that
is found in the lining of the nasal passages and
eyelids, displays a type of antibody called immunoglobulin type E (IgE) on its cell surface, and participates in the allergic response by releasing
histamine from intracellular granules.

with allergen in a test tube to determine if serum antibodies react with the allergen. Provocation testing
involves direct exposure to a likely allergen, either
through inhalation or ingestion. Positive reactions
from any of these tests may be used to narrow the
candidates for the actual allergen causing the allergy.
Identification of the allergenic substance may
allow the patient to avoid the substance and reduce
allergic reactions. In addition, allergy testing may
be done in those with asthma that is difficult to
manage, eczema, or skin rashes to determine if an
allergy is causing the condition or making it worse.
Allergy tests may also be done before allergen desensitization to ensure the safety of more extensive exposure.
Skin testing is the most common type of allergy test.
There are two forms: percutaneous and intradermal. In
percutaneous or prick testing, allergen solutions are
placed on the skin, and the skin is then pricked with a
needle, allowing the allergen to enter the skin and
become exposed to mast cells. Scratch testing, in which
the skin is scratched instead of punctured, is used less
often. Intradermal testing involves directly injecting
allergen solutions into the skin. In both tests, a reddened,
swollen spot develops at the injection site for each
129

Allergy tests

KEY TERMS

Allergy tests

substance to which the person is sensitive. Skin reactivity
is seen for allergens regardless of whether they usually
affect the skin. In other words, airborne and food allergens cause skin reactions equally well.
The range of allergens used for testing is chosen to
reflect possible sources in the environment and may
include the following:


pollen from a variety of trees, common grasses, and
weeds



mold and fungus spores



house dust



house mites



animal skin cells (dander) and saliva



food extracts



antibiotics



insect venoms

Radio-allergosorbent testing (RAST) is a laboratory test performed when a person may be too sensitive to risk skin testing or when medications or skin
conditions prevent it.
Provocation testing is done to positively identify
suspected allergens after preliminary skin testing.
A purified preparation of the allergen is inhaled or
ingested in increasing concentrations to determine if
it will provoke a response. In 2004, scientists introduced an optical method to continuously measure the
changes in nasal mucosa (lining) changes with an
infrared light to help improve the accuracy of provocation testing. Food testing is much more tedious than
inhalation testing, since full passage through the digestive system may take a day or more.

Precautions
While allergy tests are quite safe for most people,
the possibility of a condition known as anaphylaxis
exists. Anaphylaxis is a potentially dangerous condition that can result in difficulty breathing and a sharp
drop in blood pressure. People with a known history
of anaphylaxis should inform the testing clinician.
Skin tests should never include a substance known to
cause anaphylaxis in the person being tested.
Provocation tests may cause an allergic reaction.
Therefore, treatment medications should be available
following the tests, to be administered, if needed.

Description
In prick testing, a drop of each allergen to be tested
is placed on the skin, usually on the forearm or the back.
130

A close-up of a patient’s arm after allergy testing. (Custom
Medical Stock Photo. Reproduced by permission.)

A typical battery of tests may involve two dozen allergen
drops, including a drop of saline solution that should
not provoke a reaction (negative control) and a drop of
histamine that should provoke a reaction (positive control). A small needle is inserted through the drop, and
used to prick the skin below. A new needle is used for
each prick. The sites are examined over the next 20 minutes for evidence of swelling and redness, indicating a
positive reaction. In some instances, a tracing of the set
of reactions may be made by placing paper over
the tested area. Similarly, in intradermal testing, separate injections are made for each allergen tested.
Observations are made over the next 20 minutes.
In RAST testing, a blood sample is taken for use in
the laboratory, where the antibody- containing serum
is separated from the blood cells. The serum is then
exposed to allergens bound to a solid medium. If a
person has antibodies to a particular allergen, those
antibodies will bind to the solid medium and remain
behind after a rinse. Location of allergen-antibody combinations is done by adding antibody-reactive antibodies, so called anti-antibodies, that are chemically linked
with a radioactive dye. By locating radioactive spots on
the solid medium, the reactive allergens are discovered.
Provocation testing may be performed to identify
airborne or food allergens. Inhalation testing is performed only after a patient’s lung capacity and
response to the medium used to dilute the allergen
has been determined. Once this has been determined,
the patient inhales increasingly concentrated samples
of a particular allergen, followed each time by measurement of the exhalation capacity. Only one allergen
is tested per day. Testing for food allergies is usually
done by removing the suspect food from the diet for
two weeks, followed by eating a single portion of the
suspect food and follow-up monitoring.
GALE ENCYCLOPEDIA OF MEDICINE

Skin testing is preceded by a brief examination of
the skin. The patient should refrain from using antiallergy drugs for at least 48 hours before testing. Prior
to inhalation testing, patients with asthma who can
tolerate it may be asked to stop any asthma medications.
Testing for food allergies requires the person to avoid
all suspect food for at least two weeks before testing.

Gastrointestinal symptoms within 24 hours
following the ingestion of a suspected food allergen
indicates a positive response.
Resources
PERIODICALS

Hampel, U., et al. ‘‘Optical Measurements of Nasal
Swellings.’’ IEEE Transactions on Biomedical
Engineering (September 2004): 1673–1680.

Aftercare
Skin testing does not usually require any aftercare.
A generalized redness and swelling may occur in the test
area, but it will usually resolve within a day or two.
Inhalation tests may cause delayed asthma
attacks, even if the antigen administered in the test
initially produced no response. Severe initial reactions
may justify close professional observation for at least
12 hours after testing.

Richard Robinson
Teresa G. Odle

Allogenic transplant see Bone marrow
transplantation
Allopurino see Gout drugs

Risks
Intradermal testing may inadvertently result in
the injection of the allergen into the circulation, with
an increased risk of adverse reactions. Inhalation tests
may provoke an asthma attack. Exposure to new or
unsuspected allergens in any test carries the risk of
anaphylaxis. Because patients are monitored following allergy testing, an anaphylactic reaction is usually
recognized and treated promptly. Occasionally, a
delayed anaphylactic response can occur that will
require immediate care. Proper patient education
regarding how to recognize anaphylaxis is vital.

Normal results
Lack of redness or swelling on a skin test indicates
no allergic response. In an inhalation test, the exhalation capacity should remain unchanged. In a food
challenge, no symptoms should occur.

Abnormal results
Presence of redness or swelling, especially over
5 mm (1/4 inch) in diameter, indicates an allergic
response. This does not mean the substance actually
causes the patient’s symptoms, however, since he or
she may have no regular exposure to the allergen. In
fact, the actual allergen may not have been included in
the test array.
Following allergen inhalation, reduction in exhalation capacity of more than 20%, and for at least 10-20
minutes, indicates a positive reaction to the allergen.
GALE ENCYCLOPEDIA OF MEDICINE

I Alopecia
Definition
Alopecia simply means hair loss (baldness).

Description
Hair loss occurs for a great many reasons, from
conditions that make people literally pull it out to
complete hair loss caused by the toxicity of cancer
chemotherapy. Some causes are considered natural,
while others signal serious health problems. Some
conditions are confined to the scalp. Others reflect
disease throughout the body. Being plainly visible,
the skin and its components can provide early signs
of disease elsewhere in the body.
Oftentimes, conditions affecting the skin of the
scalp will result in hair loss. The first clue to the specific
cause is the pattern of hair loss, whether it be complete
baldness (alopecia totalis), patchy bald spots, thinning,
or hair loss confined to certain areas. Also a factor is
the condition of the hair and the scalp beneath it.
Sometimes only the hair is affected; sometimes the
skin is visibly diseased as well.

Causes and symptoms


Male pattern baldness (androgenic alopecia) is considered normal in adult males. It is easily recognized
by the distribution of hair loss over the top and front
of the head and by the healthy condition of the scalp.
131

Alopecia

Preparation

Alopecia

KEY TERMS
Athlete’s foot—A fungal infection between the
toes, officially known as tinea pedis.
Autoimmune disease—Certain diseases caused by
the body’s development of an immune reaction to
its own tissues.
Chemotherapy—The treatment of diseases, usually
cancer, with drugs (chemicals).
Hair follicles—Tiny organs in the skin, each one of
which grows a single hair.
Lupus erythematosus—An autoimmune disease that
can damage skin, joints, kidneys, and other organs.
Ringworm—A fungal infection of the skin, usually
known as tinea corporis.
Systemic—Affecting all or most parts of the body.

women as a result of some hairstyles that pull too
tightly on the scalp and harsh chemical treatments
that damage the hair shaft and follicles.
Top of balding male’s head. (Photograph by Kelly A. Quin.
Reproduced by permission.)



Alopecia areata is a hair loss condition of unknown
cause that can be patchy or extend to complete
baldness.



Fungal infections of the scalp usually cause patchy
hair loss. The fungus, similar to the ones that cause
athlete’s foot and ringworm, often glows under ultraviolet light.



Trichotillomania is the name of a mental disorder
that causes a person to pull out his or her own hair.



Complete hair loss is a common result of cancer
chemotherapy, due to the toxicity of the drugs used.



Systemic diseases often affect hair growth either
selectively or by altering the skin of the scalp. One
example is thyroid disorders. Hyperthyroidism
(too much thyroid hormone) causes hair to become
thin and fine. Hypothyroidism (too little thyroid
hormone) thickens both hair and skin.



Several autoimmune diseases (when protective cells
begin to attack self cells within the body) affect the
skin, notably lupus erythemematosus.



In 2004, a report a the annual meeting of the
American Academy of Dermatology said that alopecia was becoming nearly epidemic among black

132

Diagnosis
Dermatologists are skilled in diagnosis by sight
alone. For more obscure diseases, they may have to
resort to a skin biopsy, removing a tiny bit of skin using
a local anesthetic so that it can be examined under a
microscope. Systemic diseases will require a complete
evaluation by a physician, including specific tests to
identify and characterize the problem.

Treatment
Successful treatment of underlying causes is most
likely to restore hair growth, be it the completion of
chemotherapy, effective cure of a scalp fungus, or control of a systemic disease. Two relatively new drugs–
minoxidil (Rogaine) and finasteride (Proscar)–promote
hair growth in a significant minority of patients,
especially those with male pattern baldness and alopecia areata. While both drugs have so far proved to be
quite safe when used for this purpose, minoxidil is a
liquid that is applied to the scalp and finasteride is
the first and only approved treatment in a pill form.
Minoxidil was approved for over-the-counter
sales in 1996. When used continuously for long periods of time, minoxidil produces satisfactory results in
about one-fourth of patients with androgenic alopecia
and as many as half the patients with alopecia areata.
There is also an over-the-counter extra-strength
GALE ENCYCLOPEDIA OF MEDICINE

Over the past few decades a multitude of hair
replacement methods have been performed by physicians and non-physicians. They range from simply
weaving someone else’s hair in with the remains of
one’s own to surgically transplanting thousands of
hair follicles one at a time.
Hair transplantation is completed by taking tiny
plugs of skin, each containing one to several hairs,
from the back side of the scalp. The bald sections are
then implanted with the plugs. Research completed in
2000 looked at the new technique of hair grafting, and
found that micrografts (one or two hairs transplanted
per follicle) resulted in fewer complications and the
best results.
Another surgical procedure used to treat androgenic alopecia is scalp reduction. By stretching skin,
the hairless scalp can be removed and the area of bald
skin decreased by closing the space with hair-covered
scalp. Hair-bearing skin can also be folded over an
area of bald skin with a technique called a flap.
Stem cell research is generating new hope for
baldness. Scientists know that a part of the hair follicle
called the bulge contains stem cells that can give rise to
new hair and help heal skin wounds. Early research
with mice in 2004 showed promise for identifying the
genes that cause baldness and to identify drugs that
can reverse the process.

Prognosis
The prognosis varies with the cause. It is generally
much easier to lose hair than to regrow it. Even when it
returns, it is often thin and less attractive than the
original.
Resources
PERIODICALS

Cohen, Philip. ‘‘Stem Cells Generate Hair and Hope for the
Bald.’’ New Scientist (March 20, 2004): 17.
Lohr, Elizabeth. ‘‘Alopecia Nearly Epidemic Among Black
Women.’’ Clinical Psychiatry News (March 2004): 96.
Nielsen, Timothy A., and Martin Reichel. ‘‘Alopecia:
Diagnosis and Management.’’ American Family Physician.
OTHER

Androgenetic Alopecia.com. ‘‘How can minoxidil be used to
treat baldness?’’ May1, 2001. <http://androgeneticalopecia.com/baldnesstreatments/minoxidil/
002minoxidilbaldnessusee.shtml>.
GALE ENCYCLOPEDIA OF MEDICINE

Mayo Clinic. ‘‘Alopecia’’ January 26, 2001. [cited May 1,
2001]. <http://www.mayohealth.org>.
WebMD Medical News. ‘‘Hair Today, Gone Tomorrow,
Hair Again’’ 2000. [cited May 1, 2001]. <http://
my.webmd.com/content/article/1728.53923>.

Beth A. Kapes
Teresa G. Odle

I Alpha-fetoprotein test
Definition
The alpha-fetoprotein (AFP) test is a blood test
that is performed during pregnancy. This screening
test measures the level of AFP in the mother’s blood
and indicates the probability that the fetus has one
of several serious birth defects. The level of AFP can
also be determined by analyzing a sample of amniotic
fluid. This screening test cannot diagnose a specific
condition; it only indicates increased risk for several
birth defects. Outside pregnancy, the AFP test is used
to detect liver disease, certain cancerous tumors, and
to monitor the progress of cancer treatment.

Purpose
Alpha-fetoprotein is a substance produced by the
liver of a fetus. The exact function of this protein is
unknown. After birth, the infant’s liver stops producing
AFP, and an adult liver contains only trace amounts.
During pregnancy, the fetus excretes AFP in urine and
some of the protein crosses the fetal membranes to
enter the mother’s blood. The level of AFP can then
be determined by analyzing a sample of the mother’s
blood. By analyzing the amount of AFP found in a
blood or amniotic fluid sample, doctors can determine
the probability that the fetus is at risk for certain birth
defects. It is very important that the doctor know
precisely how old the fetus is when the test is performed
since the AFP level changes over the length of the
pregnancy. Alone, AFP screening cannot diagnose a
birth defect. The test is used as an indicator of risk and
then an appropriate line of testing (such as amniocentesis or ultrasound) follows, based on the results.
Abnormally high AFP may indicate that the
fetus has an increased risk of a neural tube defect,
the most common and severe type of disorder
associated with increased AFP. These types of defects
include spinal column defects (spina bifida) and
anencephaly (a severe and usually fatal brain
abnormality). If the tube that becomes the brain
133

Alpha-fetoprotein test

version of minoxidil (5% concentration) approved for
use by men only. The treatment often results in new
hair that is thinner and lighter in color. It is important
to note that new hair stops growing soon after the use
of minoxidil is discontinued.

Alpha-fetoprotein test

KEY TERMS
Amniotic fluid—Fluid within the uterine sac in
which the fetus lives until born.
Fetus—The stage in human development from the
second month of pregnancy until birth.

reappear in liver disease, or tumors of the liver, ovaries, or testicles. The AFP test is used to screen people
at high risk for these conditions. After a cancerous
tumor is removed, an AFP test can monitor the
progress of treatment. Continued high AFP levels
suggest the cancer is growing.

Precautions
and spinal cord does not close correctly during fetal
development, AFP may leak through this abnormal
opening and enter the amniotic fluid. This leakage
creates abnormally high levels of AFP in amniotic
fluid and in maternal blood. If the screening test
indicates abnormally high AFP, ultrasound is used
to diagnose the problem.
Other fetal conditions that can raise AFP levels
above normal include:


cysts at the end of the spine



blockage in the esophagus or intestines



liver disease causing liver cells to die



defects in the abdominal wall



kidney or urinary tract defects or disease



brittle bone disease

Levels may also be high if there is too little fluid in
the amniotic sac around the fetus, more than one
developing fetus, or a pregnancy that is farther along
than estimated.
For unknown reasons, abnormally low AFP may
indicate that the fetus has an increased risk of Down
syndrome. Down syndrome is a condition that includes
mental retardation and a distinctive physical appearance
linked to an abnormality of chromosome 21 (called
trisomy 21). If the screening test indicates an abnormally
low AFP, amniocentesis is used to diagnose the problem.
Abnormally low levels of AFP can also occur when
the fetus has died or when the mother is overweight.
AFP is often part of a ‘‘triple check’’ blood test
that analyzes three substances as risk indicators of
possible birth defects: AFP, estriol, and human chorionic gonadotropin (HCG). When all three substances
are measured in the mother’s blood, the accuracy of
the test results increases.
In 2004, a new study showed that the risk of an
infant’s death from sudden infant death syndrome
(SIDS) increased if levels of AFP were higher during
the second trimester of the mother’s pregnancy.
Although AFP in human blood gradually disappears after birth, it never disappears entirely. It may
134

It is very important that the doctor know precisely
how old the fetus is when the test is performed since
the AFP level considered normal changes over the
length of the pregnancy. Errors in determining the
age of the fetus lead to errors when interpreting
the test results. Since an AFP test is only a screening
tool, more specific tests must follow to make an accurate diagnosis. An abnormal test result does not necessarily mean that the fetus has a birth defect. The test
has a high rate of abnormal results (either high or low)
to prevent missing a fetus that has a serious condition.

Description
The AFP test is usually performed at week 16 of
pregnancy. Blood is drawn from the patient’s
(mother’s) vein, usually on the inside of the elbow.
AFP can also be measured in the sample of amniotic
fluid taken at the time of amniocentesis. Test results
are usually available after about one week.

Preparation
There is no specific physical preparation for the
AFP test.

Aftercare
There is no specific aftercare involved with this
screening test.

Risks
The risks associated with drawing blood are minimal, but may include bleeding from the puncture
site, feeling faint or lightheaded after the blood is
drawn, or blood accumulating under the puncture
site (hematoma).

Normal results
Alpha-fetoprotein is measured in nanograms per
milliliter (ng/mL) and is expressed as a probability.
The probability (1:100, for example) translates into
the chance that the fetus has a defect (a one in 100
chance, for example).
GALE ENCYCLOPEDIA OF MEDICINE

Abnormal results
The doctor will inform the woman of her specific
increased risk as compared to the ‘‘normal’’ risk of a
standard case. If the risk of Down syndrome is greater
than the standard risk for women who are 35 years old
or older (one in 270), amniocentesis is recommended.
Again, the test has a high rate of showing an abnormal
AFP level in order to prevent missing a fetus that has
Down’s syndrome. This screening test only predicts
risk; appropriate diagnostic testing will follow after an
abnormal screening result.
In tumor or liver disease testing, an AFP level
greater than 50 ng/mL is considered abnormal.
Resources

Purpose
These drugs, called alpha blockers for short, are
used for two main purposes: to treat high blood pressure (hypertension) and to treat benign prostatic
hyperplasia (BPH), a condition that affects men and
is characterized by an enlarged prostate gland.
High blood pressure
High blood pressure puts a strain on the heart and
the arteries. Over time, hypertension can damage the
blood vessels to the point of causing stroke, heart failure or kidney failure. People with high blood pressure
may also be at higher risk for heart attacks.
Controlling high blood pressure makes these problems
less likely. Alpha blockers help lower blood pressure
by causing vasodilation, meaning an increase in the
diameter of the blood vessels, which allows blood to
flow more easily.
Benign prostatic hyperplasia (BPH)

PERIODICALS

Smith, Gordon C.S., et al. ‘‘Second-trimester Maternal
Serum Levels of Alpha-fetoprotein and the Subsequent
Risk of Sudden Infant Death Syndrome.’’ New England
Journal of Medicine (September 2, 2004): 978.
ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914)
428-7100. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

This condition particularly affects older men.
Over time, the prostate, a donut-shaped gland
below the bladder, enlarges. When this happens, it
may interfere with the passage of urine from the
bladder out of the body. Men who are diagnosed
with BPH may have to urinate more often. Or they
may feel that they can not completely empty their
bladders. Alpha blockers inhibit the contraction of
prostatic smooth muscle and thus relax muscles in
the prostate and the bladder, allowing urine to flow
more freely.

Description
Adrienne Massel, RN
Teresa G. Odle

Alpha-thalassemia see Thalassemia

Commonly prescribed alpha blockers for hypertension and BPH include doxazosin (Cardura, prazosin (Minipress) and terazosin (Hytrin). Prazosin is also
used in the treatment of heart failure. All are available
only with a physician’s prescription and are sold in
tablet form.

Recommended dosage

I Alpha -adrenergic blockers
1

Definition
Alpha1-adrenergic blockers are drugs that work
by blocking the alpha1-receptors of vascular smooth
muscle, thus preventing the uptake of catecholamines
by the smooth muscle cells. This causes vasodilation
and allows blood to flow more easily.
GALE ENCYCLOPEDIA OF MEDICINE

The recommended dose depends on the patient
and the type of alpha blocker and may change over
the course of treatment. The prescribing physician will
gradually increase the dosage, if necessary. Some
patients may need as much as 15-20 mg per day of
terazosin, 16 mg per day of doxazosin, or as much as
40 mg per day of prazosin, but most people benefit
from lower doses. As the dosage increases, so does the
possibility of unwanted side effects.
135

Alpha1-adrenergic blockers

When testing for cancer or liver diseases, AFP
results are reported as nanograms per milliliter. An
AFP level less than or equal to 50 ng/mL is considered
normal.

Alpha1-adrenergic blockers

KEY TERMS
Adrenergic—Refers to neurons (nerve cells) that use
catecholamines as neurotransmitters at a synapse.
Adrenergic receptor—There are three families of
adrenergic receptors, alpha1, alpha2 and beta, and
each family contains three distinct subtypes. Each of
the nine subtypes are coded by separate genes, and
display specific drug specificities and regulatory
properties.
Alpha blockers—Medications that bind alpha adrenergic receptors and decrease the workload of the
heart and lower blood pressure. They are commonly
used to treat hypertension, peripheral vascular disease, and hyperplasia.
Arteries—Blood vessels that carry oxygenated blood
away from the heart to the cells, tissues, and organs
of the body.
Catecholamines—Family of neurotransmitters containing dopamine, norepinephrine and epinephrine,
produced and secreted by cells of the adrenal
medulla in the brain. Catecholamines have excitatory effects on smooth muscle cells of the vessels that
supply blood to the skin and mucous membranes
and have inhibitory effects on smooth muscle cells
located in the wall of the gut, the bronchial tree of the
lungs, and the vessels that supply blood to skeletal

Alpha blockers should be taken exactly as directed, even if the medication does not seem to be working at first. It should not be stopped even if symptoms
improve because it needs to be taken regularly to be
effective. Patients should avoid missing any doses, and
should not take larger or more frequent doses to make
up for missed doses.

Precautions
Alpha blockers may lower blood pressure to a
greater extent than desired. This can cause dizziness,
lightheadedness, heart palpitations, and fainting.
Activities such as driving, using machines, or doing
anything else that might be dangerous for 24 hours
after taking the first dose should be avoided. Patients
should be reminded to be especially careful not to
fall when getting up in the middle of the night. The
same precautions are recommended if the dosage
is increased or if the drug has been stopped and
then started again. Anyone whose safety on the job
could be affected by taking alpha blockers should
136

muscle. There are two different main types of receptors for these neurotransmitters, called alpha and beta
adrenergic receptors. The catecholamines are therefore are also known as adrenergic neurotransmitters.
Hyperplasia—The abnormal increase in the number
of normal cells in a given tissue.
Hypertension—Persistently
pressure.

high

arterial

blood

Neurotransmitter—Substance released from neurons
of the peripheral nervous system that travels across
the synaptic clefts (gaps) of other neurons to excite or
inhibit the target cell.
Palpitation—Rapid, forceful, throbbing, or fluttering
heartbeat.
Receptor—A molecular structure in a cell or on the
surface of a cell that allows binding of a specific
substance that causes a specific physiologic response.
Synapse—A connection between nerve cells, by
which nervous excitation is transferred from one
cell to the other.
Vasodilation—The increase in the internal diameter
of a blood vessel that results from relaxation of
smooth muscle within the wall of the vessel thus
causing an increase in blood flow.

inform his or her physician, so that the physician
can take this factor into account when increasing
dosage.
Some people may feel drowsy or less alert when
using these drugs. They should accordingly avoid
driving or performing activities that require full
attention.
People diagnosed with kidney disease or liver disease may also be more sensitive to alpha blockers.
They should inform their physicians about these conditions if alpha blockers are prescribed. Older people
may also be more sensitive and may be more likely to
have unwanted side effects, such as fainting, dizziness,
and lightheadedness.
It should be noted that alpha blockers do not cure
high blood pressure. They simply help to keep the
condition under control. Similarly, these drugs will
not shrink an enlarged prostate gland. Although they
will help relieve the symptoms of prostate enlargement, the prostate may continue to grow, and it eventually may be necessary to have prostate surgery.
GALE ENCYCLOPEDIA OF MEDICINE

Anyone who has had unusual reactions to alpha
blockers in the past should let his or her physician
know before taking the drugs again. The physician
should also be told about any allergies to foods,
dyes, preservatives, or other substances.
The effects of taking alpha blockers during pregnancy are not fully understood. Women who are pregnant or planning to become pregnant should inform
their physicians. Breastfeeding mothers who need to
take alpha blockers should also talk to their physicians. These drugs can pass into breast milk and may
affect nursing babies. It may be necessary to stop
breastfeeding while being treated with alpha blockers.

Side effects
The most common side effects are dizziness, drowsiness, tiredness, headache, nervousness, irritability,
stuffy or runny nose, nausea, pain in the arms and legs,
and weakness. These problems usually go away as the
body adjusts to the drug and do not require medical
treatment. If they do not subside or if they interfere with
normal activities, the physician should be informed.
If any of the following side effects occur, the prescribing physician should be notified as soon as possible:


fainting



shortness of breath or difficulty breathing



fast, pounding, or irregular heartbeat



swollen feet, ankles, wrists

Other side effects may occur. Anyone who has
unusual symptoms after taking alpha blockers should
contact his or her physician.

Interactions
Doxazosin (Cardura) is not known to interact
with any other drugs. Terazosin (Hytrin) may interact
with nonsteroidal anti-inflammatory drugs, such as
ibuprofen (Motrin), and with other blood pressure
drugs, such as enalapril (Vasotec), and verapamil
(Calan,Verelan). Prazosin (Minipress) may interact
with beta adrenergic blocking agents such as propranolol (Inderal) and others, and with verapamil (Calan,
Isoptin.) When drugs interact, the effects of one or
both of the drugs may change or the risk of side effects
may be greater.
Nancy Ross-Flanigan
GALE ENCYCLOPEDIA OF MEDICINE

I Alport syndrome
Definition
A hereditary disease of the kidneys that primarily
affects men, causing blood in the urine, hearing loss
and eye problems. Eventually, kidney dialysis or transplant may be necessary.

Description
Alport syndrome affects about one in 5,000
Americans, striking men more often and severely
than women. There are several varieties of the syndrome, some occurring in childhood and others not
causing symptoms until men reach their 20s or 30s. All
varieties of the syndrome are characterized by kidney
disease that usually progresses to chronic kidney failure and by uremia (the presence of excessive amounts
of urea and other waste products in the blood).

Causes and symptoms
Alport syndrome in most cases is caused by a
defect in one or more genes located on the X chromosome. It is usually inherited from the mother, who is a
normal carrier. However, in up to 20% of cases there is
no family history of the disorder. In these cases, there
appears to be a spontaneous genetic mutation causing
Alport syndrome.
Blood in the urine (hematuria) is a hallmark of
Alport syndrome. Other symptoms that may appear in
varying combinations include:


protein in the urine (proteinuria)



sensorineural hearing loss



eye problems [involuntary, rhythmic eye movements
(nystagmus), cataracts, or cornea problems]



skin problems



platelet disorders



abnormal white blood cells



smooth muscle tumors

Not all patients with Alport syndrome have hearing problems. In general, those with normal hearing
have less severe cases of Alport syndrome.

Diagnosis
Alport syndrome is diagnosed with a medical evaluation and family history, together with a kidney
biopsy that can detect changes in the kidney typical of
137

Alport syndrome

Alpha blockers may lower blood counts. Patients
may need to have their blood checked regularly while
taking this medicine.

Alport syndrome

KEY TERMS
Albumin—A protein that is important in maintaining blood volume. Low albumin levels is one sign
of Alport syndrome.
Dialysis—A technique of removing waste material
from the blood. It is used with patients whose kidneys have stopped functioning and can no longer
cleanse the blood on their own.
Diuretic—A drug that increases the amount of
urine a person produces.
Hematuria—Blood in the urine, Hematuria is a
hallmark of Alport syndrome.
Pulmonary edema—Excess fluid in the air spaces of
the lungs.
Uremia—The presence of excessive amounts of
urea and other waste products in the blood.

the condition. Urinalysis may reveal blood or protein in
the urine. Blood tests can reveal a low platelet level.
In addition, tests for the Alport gene are now
available. Although testing is fairly expensive, it is
covered by many types of health insurance. DNA
tests can diagnose affected children even before birth,
and genetic linkage tests tracing all family members at
risk for Alport syndrome are also available.

The treatment for chronic kidney failure is dialysis
or a kidney transplant.

Prognosis
Women with this condition can lead a normal life,
although they may have slight hearing loss. An
affected woman may notice blood in her urine only
when under stress or pregnant.
Men generally have a much more serious problem
with the disease. Most will experience kidney disease
in their 20s or 30s, which may eventually require dialysis or transplantation, and many develop significant
hearing loss. Men with Alport syndrome often die of
complications by middle age.

Prevention
Alport syndrome is a genetic disease and prevention efforts are aimed at providing affected individuals
and their families with information concerning the
genetic mechanisms responsible for the disease. Since
it is possible to determine if a woman is a carrier, or if
an unborn child has the condition, genetic counseling
can provide helpful information and support for the
decisions that affected individuals and their families
may have to make.
Resources
ORGANIZATIONS

Treatment
There is no specific treatment that can ‘‘cure’’
Alport syndrome. Instead, care is aimed at easing the
problems related to kidney failure, such as the presence
of too many waste products in the blood (uremia).
To control kidney inflammation (nephritis),
patients should:


restrict fluids



control high blood pressure



manage pulmonary edema



control high blood levels of potassium

Rarely patients with Alport syndrome may develop
nephrotic syndrome, a group of symptoms including
too much protein in the urine, low albumin levels, and
swelling. To ease these symptoms, patients should:


drink less



eat a salt-free diet



use diuretics



have albumin transfusions

138

American Association of Kidney Patients. 100 S. Ashley Dr.,
#280, Tampa, FL 33602. (800) 749-2257. <http://
www.aakp.org>.
American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney and Urologic Disease Information
Clearinghouse. 3 Information Way, Bethesda, MD
20892. (301) 654-4415. <http://www.niddk.nih.gov>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.
National Organization for Rare Diseases. P.O. Box 8923,
Fairfield, CT 06812. (213) 745-6518. <http://
www.w2.com>.
OTHER

Alport Syndrome Home Page. <http://www.cc.utah.edu/
~cla6202/ASHP.htm>.
‘‘Alport Syndrome.’’ Pediatric Database Home Page.
<http://www.icondata.com/health/pedbase/files/
ALPORTSY.HTM>.
The Hereditary Nephritis Foundation (HNF) Home Page.
<http://www.cc.utah.edu/~cla6202/HNF.htm>.

Carol A. Turkington
GALE ENCYCLOPEDIA OF MEDICINE

ALS see Amyotrophic lateral sclerosis
Alteplase see Thrombolytic therapy

KEY TERMS
Cerebral—Pertaining to the brain.
Edema—Accumulation of excess fluid in the tissues
of the body.
Hypoxemia—Insufficient oxygenation of the blood.

I Altitude sickness
Definition
Altitude sickness is a general term encompassing a
spectrum of disorders that occur at higher altitudes.
Since the severity of symptoms varies with altitude, it
is important to understand the range of the different
altitudes that may be involved. High altitude is defined
as height greater than 8,000 feet (2,438m); medium
altitude is defined as height between 5,000 and 8,000
feet (1,524-2,438m); and extreme altitude is defined as
height greater than 19,000 feet (5,791 m). The majority
of healthy individuals suffer from altitude sickness when
they reach very high altitudes. In addition, about 20%
of people ascending above 9,000 feet (2,743m) in one
day will develop altitude sickness. Children under six
years and women in the premenstrual part of their cycles
may be more vulnerable. Individuals with preexisting
medical conditions–even a minor respiratory infection–
may become sick at more moderate altitudes.

Description
There are three major clinical syndromes that fall
under the heading of altitude sickness: acute mountain
sickness (AMS), high-altitude pulmonary edema
(HAPE), and high-altitude cerebral edema (HACE).
These syndromes are not separate, individual syndromes as much as they are a continuum of severity,
all resulting from a decrease in oxygen in the air. AMS
is the mildest, and the other two represent severe, lifethreatening forms of altitude sickness.
Altitude sickness occurs because the partial pressure of oxygen decreases with altitude. (Partial pressure is a term applied to gases that is similar to the way
the term concentration is applied to liquid solutions.)
For instance, at 18,000 feet (5,486 m) the partial pressure of oxygen drops to one-half its value at sea level
and, therefore, there is a substantially lower amount of
oxygen available for the individual to inhale. This is
known as hypoxia. Furthermore, since there is less
oxygen to inhale, less oxygen reaches the blood. This
is known as hypoxemia. These two conditions are the
major factors that form the basis for all the medical
problems associated with altitude sickness.
GALE ENCYCLOPEDIA OF MEDICINE

Hypoxia—A deficiency in the amount of oxygen
required for effective ventilation.
Pulmonary—Pertaining to the lungs.

As a person becomes hypoxemic, his natural
response is to breathe more rapidly (hyperventilate).
This is the body’s attempt to bring in more oxygen at
a rapid rate. This attempt at alleviating the effects of the
hypoxia at higher altitudes is known as acclimatization,
and it occurs during the first few days. Acclimatization
is a response that occurs in individuals who travel from
lower to higher altitudes. There are groups of people
who have lived at high altitudes (for example, in the
Himalayan and Andes mountains) for generations, and
they are simply accustomed to living at such altitudes,
perhaps through a genetic ability.

Causes and symptoms
Acute mountain sickness (AMS) is a mild form of
altitude sickness that results from ascent to altitudes
higher greater than 8,000 feet (2,438m)–even 6,500 feet
(1,981 m) in some susceptible individuals. Although
hypoxia is associated with the development of AMS,
the exact mechanism by which this condition develops
has yet to be confirmed. It is important to realize that
some individuals acclimatize to higher altitudes more
efficiently than others. As a result, under similar conditions some will suffer from AMS while others will not.
At present, the susceptibility of otherwise healthy individuals to contracting AMS cannot be accurately predicted. Of those who do suffer from AMS, the condition
tends to be most severe on the second or third day after
reaching the high altitude, and it usually abates after
three to five days if they remain at the same
altitude. However, it can recur if the individuals travel
to an even higher altitude. Symptoms usually appear a
few hours to a few days following ascent, and they
include dizziness, headache, shortness of breath, nausea,
vomiting, loss of appetite, and insomnia.
High-altitude pulmonary edema (HAPE) is a lifethreatening condition that afflicts a small percentage
of those who suffer from AMS. In this condition, fluid
leaks from within the pulmonary blood vessels into the
lung tissue. As this fluid begins to accumulate within
139

Altitude sickness

Alprazolam see Benzodiazepines

Alzheimer’s disease

the lung tissue (pulmonary edema), the individual
begins to become more and more short of breath.
HAPE is known to afflict all types of individuals,
regardless of their level of physical fitness.
Typically, the individual who suffers from HAPE
ascends quickly to a high altitude and almost immediately develops shortness of breath, a rapid heart
rate, a cough productive of a large amount of sometimes bloody sputum, and a rapid rate of breathing.
If no medical assistance is provided by this point,
the patient goes into a coma and dies within a few
hours.
High-altitude cerebral edema (HACE), the rarest
and most severe form of altitude sickness, involves
cerebral edema, and its mechanism of development is
also poorly understood. The symptoms often begin
with those of AMS, but neurologic symptoms such
as an altered level of consciousness, speech abnormalities, severe headache, loss of coordination, hallucinations, and even seizures. If no intervention is
implemented, death is the result.

Diagnosis
The diagnosis for altitude sickness may be made
from the observation of the individual’s symptoms
during travel to higher altitudes.

Prevention
When individuals ascend from sea level, it is recommended that they spend at least one night at
an intermediate altitude prior to ascending to higher
elevations. In general, climbers should take at least two
days to go from sea level to 8,000 feet (2,438m). After
reaching that point, healthy climbers should generally
allow one day for each additional 2,000 feet (610m), and
one day of rest should be taken every two or three days.
Should mild symptoms begin to surface, further ascent
should be avoided. If the symptoms are severe, the individual should return to a lower altitude. Some reports
indicate that acetazolamide (a diuretic) may be taken
before ascent as a preventative measure for AMS.
Paying attention to diet can also help prevent altitude sickness. Water loss is a problem at higher altitudes, so climbers should drink ample water (enough to
produce copious amounts of relatively light-colored or
clear urine). Alcohol and large amounts of salt should
be avoided. Eating frequent small, high-carbohydrate
snacks (for example, fruits, jams and starchy foods)
can help, especially in the first few days of climbing.
Resources
BOOKS

Crystal, R. G., et al., editors. The Lung: Scientific
Foundations. Lippincott-Raven Publishers, 1997.

Treatment
Mild AMS requires no treatment other than an
aspirin or ibuprofen for headache, and avoidance of
further ascent. Narcotics should be avoided because
they may blunt the respiratory response, making
it even more difficult for the person to breathe deeply
and rapidly enough to compensate for the lower levels
of oxygen in the environment. Oxygen may also be
used to alleviate symptoms of mild AMS.
As for HAPE and HACE, the most important
course of action is descent to a lower altitude as soon
as possible. Even a 1,000-2,000-foot (305-610 m) descent can dramatically improve one’s symptoms. If
descent is not possible, oxygen therapy should be
started. In addition, dexamethasone (a steroid) has
been suggested in order to reduce cerebral edema.

Kapil Gupta, MD

Aluminum hydroxide see Antacids

I Alzheimer’s disease
Definition
Alzheimer’s disease (AD) is the most common form
of dementia, a neurologic disease characterized by loss
of mental ability severe enough to interfere with normal
activities of daily living, lasting at least six months, and
not present from birth. AD usually occurs in old age,
and is marked by a decline in cognitive functions such as
remembering, reasoning, and planning.

Prognosis
The prognosis for mild AMS is good, if appropriate measures are taken. As for HAPE and HACE,
the prognosis depends upon the rapidity and distance
of descent and the availability of medical intervention.
Descent often leads to improvement of symptoms,
however, recovery times vary among individuals.
140

Description
A person with AD usually has a gradual decline in
mental functions, often beginning with slight memory
loss, followed by losses in the ability to maintain
employment, to plan and execute familiar tasks, and to
reason and exercise judgment. Communication ability,
GALE ENCYCLOPEDIA OF MEDICINE

The cost of caring for a person with AD is considerable. The annual cost of caring for one AD
patient in 1998 was estimated as about $18,400 for a
patient with mild AD, $30,100 for a patient with moderate AD, and $36,100 for a patient with severe AD.
The annual direct and indirect costs of caring for AD
patients in the United States was estimated to be as
much as $100 billion. Slightly more than half of people
with AD are cared for at home, while the remainder
are cared for in a variety of health care institutions.

Causes and symptoms
Causes
The cause or causes of Alzheimer’s disease are largely unknown, though some forms have genetic links.
Some strong leads have been found through recent
research, however, and these have given some theoretical support to several new experimental treatments.

A brain segment affected by Alzheimer’s disease on the right
compared with a healthy brain segment (left). The diseased
brain appears shrunken, and the fissures are noticeably
larger. (Simon Fraser/MRC Unit, Newcastle General Hospital/
Science Photo Library. Photo Researchers, Inc. Reproduced by
permission.)

mood, and personality also may be affected. Most
people who have AD die within eight years of their
diagnosis, although the interval may be as short as one
year or as long as 20 years. AD is the fourth leading
cause of death in adults after heart disease, cancer, and
stroke.
Between two and four million Americans have
AD; that number is expected to grow to as many as
14 million by the middle of the 21st century as the
population ages. While a small number of people in
their 40s and 50s develop the disease (called earlyonset AD), AD predominantly affects the elderly.
AD affects about 3% of all people between ages 65
and 74, about 19% of those between 75 and 84, and
about 47% of those over 85. Slightly more women
than men are affected with AD, but this may be
GALE ENCYCLOPEDIA OF MEDICINE

At first AD destroys neurons (nerve cells) in parts
of the brain that control memory, including the
hippocampus, which is a structure deep in the deep
that controls short-term memory. As these neurons
in the hippocampus stop functioning, the person’s
short-term memory fails, and the ability to perform
familiar tasks decreases. Later AD affects the cerebral
cortex, particularly the areas responsible for language
and reasoning. Many language skills are lost and the
ability to make judgments is affected. Personality
changes occur, which may include emotional outbursts, wandering, and agitation. The severity of
these changes increases with disease progression.
Eventually many other areas of the brain become
involved, the brain regions affected atrophy (shrink
and lose function), and the person with AD becomes
bedridden, incontinent, helpless, and non-responsive.
Autopsy of a person with AD shows that the
regions of the brain affected by the disease become
clogged with two abnormal structures, called neurofibrillary tangles and amyloid plaques. Neurofibrillary
tangles are twisted masses of protein fibers inside nerve
cells, or neurons. In AD, tau proteins, which normally
help bind and stabilize parts of neurons, are changed
chemically, become twisted and tangled, and no longer
can stabilize the neurons. Amyloid plaques consist of
insoluble deposits of beta-amyloid, (a protein fragment
from a larger protein called amyloid precursor protein
(APP), mixed with parts of neurons and non-nerve
cells. Plaques are found in the spaces between the
nerve cells of the brain. While it is not clear exactly
141

Alzheimer’s disease

because women tend to live longer, leaving a higher
proportion of women in the most affected age groups.

Alzheimer’s disease
Diseased tissue from the brain of an Alzheimer’s patient showing senile plaques within the brain’s gray matter. (Photograph by
Cecil Fox, Photo Researchers, Inc. Reproduced by permission.)

KEY TERMS
Acetylcholine—One of the substances in the body
that helps transmit nerve impulses.
Dementia—Impaired intellectual function that
interferes with normal social and work activities.
Ginkgo—An herb from the Ginkgo biloba tree that
some alternative practitioners recommend for the
prevention and treatment of AD.
Neurofibrillary tangle—Twisted masses of protein
inside nerve cells that develop in the brains of
people with AD.
Senile plaque—Structures composed of parts of
neurons surrounding brain proteins called betaamyloid deposits found in the brains of people
with AD.

how these structures cause problems, many researchers
believe that their formation is responsible for the mental changes of AD, presumably by interfering with the
normal communication between neurons in the brain
and later leading to the death of neurons. By 2000,
three drugs for the treatment of AD symptoms were
approved by the U.S. Food and Drug Administration
(FDA). They act by increasing the level of chemical
signaling molecules in the brain, known as neurotransmitters, to make up for this decreased communication
ability. All act by inhibiting the activity of acetylcholinesterase, which is an enzyme that breaks down
acetylcholine, an important neurotransmitter released
by neurons that is necessary for cognitive function.
These drugs modestly increase cognition and improve
one’s ability to perform normal activities of daily living.
142

Exactly what triggers the formation of plaques
and tangles and the development of AD is unknown.
AD likely results from many interrelated factors,
including genetic, environmental, and others not yet
identified. Two types of AD exist: familial AD (FAD),
which is a rare autosomal dominant inherited disease,
and sporadic AD, with no obvious inheritance pattern. AD also is described in terms of age at onset, with
early onset AD occurring in people younger than 65,
and late-onset occurring in those 65 and older. Early
onset AD comprises about 5-10 % of AD cases and
affects people aged 30 to 60. Some cases of early onset
AD are inherited and are common in some families.
Early-onset AD often progresses faster than the more
common late-onset type.
All cases of FAD, which is relatively uncommon,
that have been identified to date are the early onset
type. As many as 50% of FAD cases are known to
be caused by three genes located on three different
chromosomes. Some families have mutations in the
APP gene located on chromosome 21, which causes
the production of abnormal APP protein. Others
have mutations in a gene called presenilin 1 located
on chromosome 14, which causes the production of
abnormal presenilin 1 protein, and others have mutations in a similar gene called presenilin 2 located
on chromosome 1, which causes production of abnormal presenilin 2. Presenilin 1 may be one of the
enzymes that clips APP into beta-amyloid; it also
may be important in the synaptic connections between
brain cells.
There is no evidence that the mutated genes that
cause early onset FAD also cause late onset AD, but
genetics appears to play a role in this more common
form of AD. Discovered by researchers at Duke
University in the early 1990s, potentially the most
important genetic link to AD was on chromosome 19.
A gene on this chromosome, called APOE (apolipoprotein E), codes for a protein involved in transporting
lipids into neurons. APOE occurs in at least three forms
(alleles), called APOE e2, APOE e3, and APOE e4.
Each person inherits one APOE from each parent, and
therefore can either have one copy of two different
forms, or two copies of one. The relatively rare APOE
e2 appears to protect some people from AD, as it seems
to be associated with a lower risk of AD and a later age
of onset if AD develops. APOE e3 is the most common
version found in the general population, and only
appears to have a neutral role in AD. However, APOE
e4 appears to increase the risk of developing late onset
AD with the inheritance of one or two copies of APOE
e4. Compared to those without APOE e4, people with
one copy are about three times as likely to develop lateGALE ENCYCLOPEDIA OF MEDICINE

Other non-genetic factors have been studied in
relation to the causes of AD. Inflammation of the
brain may play a role in development of AD, and use
of nonsteroidal anti-inflammatory drugs (NSAIDs)
were once thought to reduce the risk of developing
AD. Other agents once thought to reduce chances of
dementia are now thought to increase its risk. In 2002,
hormone replacement therapy (HRT), which combines
estrogen and progestogen, was found to double the
risk of developing dementia in postmenopausal
women. Highly reactive molecular fragments called
free radicals damage cells of all kinds, especially
brain cells, which have smaller supplies of protective
antioxidants thought to protect against free radical
damage. Vitamin E is one such antioxidant, and its
use in AD may be of possible theoretical benefit.
While the ultimate cause or causes of Alzheimer’s
disease still are unknown, there are several risk factors
that increase a person’s likelihood of developing the
disease. The most significant one is, of course, age;
older people develop AD at much higher rates than
younger ones. There is some evidence that strokes and
AD may be linked, with small strokes that go undetected clinically contributing to the injury of neurons.
A 2003 Dutch study reported that symptomless, unnoticed strokes could double the risk of AD and other
dementias. Blood cholesterol levels also may be
important. Scientists have shown that high blood
cholesterol levels in special breeds of genetically
engineered (transgenic) mice may increase the rate of
plaque deposition. There are also parallels between
AD and other progressive neurodegenerative disorders that cause dementia, including prion diseases,
Parkinson’s disease, and Huntington’s disease.
GALE ENCYCLOPEDIA OF MEDICINE

Numerous epidemiological studies of populations
also are being conducted to learn more about whether
and to what extent early life events, socioeconomic
factors, and ethnicity have an impact on the development of AD. For example, a 2003 report showed that
the more formal education a person has, the better his
or her memory is, despite presence of AD. Other studies have related education level or participation in
leisure activities such as playing cards or doing crossword puzzles to delayed onset of AD.
Many environmental factors have been suspected
of contributing to AD, but epidemiological population studies have not borne out these links. Among
these have been pollutants in drinking water, aluminum from commercial products, and metal dental fillings. To date, none of these factors has been shown to
cause AD or increase its likelihood. Further research
may yet turn up links to other environmental factors.
Symptoms
The symptoms of Alzheimer’s disease begin gradually, usually with memory lapses. Occasional memory lapses are of course common to everyone, and do
not by themselves signify any change in cognitive
function. The person with AD may begin with only
the routine sort of memory lapse — forgetting where
the car keys are — but progress to more profound or
disturbing losses, such as forgetting that he or she can
even drive a car. Becoming lost or disoriented on a walk
around the neighborhood becomes more likely as the
disease progresses. A person with AD may forget the
names of family members, or forget what was said at
the beginning of a sentence by the time he hears the end.
As AD progresses, other symptoms appear,
including inability to perform routine tasks, loss of
judgment, and personality or behavior changes.
Some people with AD have trouble sleeping and may
suffer from confusion or agitation in the evening
(‘‘sunsetting’’ or Sundowner’s Syndrome). In some
cases, people with AD repeat the same ideas, movements, words, or thoughts. In the final stages people
may have severe problems with eating, communicating, and controlling their bladder and bowel functions.
The Alzheimer’s Association has developed a list
of 10 warning signs of AD. A person with several of
these symptoms should see a physician for a thorough
evaluation:


memory loss that affects job skills



difficulty performing familiar tasks



problems with language



disorientation of time and place
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Alzheimer’s disease

onset AD, and those with two copies are almost four
times as likely to do so. Having APOE e4 also can lower
the age of onset by as much as 17 years. However,
APOE e4 only increases the risk of developing AD
and does not cause it, as not everyone with APOE e4
develops AD, and people without it can still have the
disease. Why APOE e4 increases the chances of developing AD is not known with certainty. However, one
theory is that APOE e4 facilitates beta-amyloid buildup
in plaques, thus contributing to the lowering of the age
of onset of AD; other theories involve interactions with
cholesterol levels and effects on nerve cell death independent of its effects on plaque buildup. In 2000, four
new AD-related regions in the human genome were
identified, where one out of several hundred genes in
each of these regions may be a risk factor gene for AD.
These genes, which are not yet identified, appear to
make a contribution to the risk of developing lateonset AD that is at least as important as APOE e4.

Alzheimer’s disease



poor or decreased judgment



problems with abstract thinking



misplacing things



changes in mood or behavior



changes in personality



loss of initiative

Other types of dementia, including some that are
reversible, can cause similar symptoms. It is important for the person with these symptoms to be evaluated by a professional who can weigh the possibility
that his or her symptoms may have another cause.
Approximately 20% of those originally suspected of
having AD turn out to have some other disorder;
about half of these cases are treatable.

Diagnosis
Diagnosis of Alzheimer’s disease is complex, and
may require office visits to several different specialists
over several months before a diagnosis can be made.
While a confident provisional diagnosis may be made
in most cases after thorough testing, AD cannot be
diagnosed definitively until autopsy examination of
the brain for plaques and neurofibrillary tangles.
The diagnosis of AD begins with a thorough
physical exam and complete medical history. Except
in the disease’s earliest stages, accurate history from
family members or caregivers is essential. Since there
are both prescription and over-the-counter drugs
that can cause the same mental changes as AD, a
careful review of the patient’s drug, medicine, and
alcohol use is important. AD-like symptoms also
can be provoked by other medical conditions, including tumors, infection, and dementia caused by mild
strokes (multi-infarct dementia). These possibilities
must be ruled out as well through appropriate blood
and urine tests, brain magnetic resonance imaging
(MRI), positron emission tomography (PET) or single photon emission computed tomography (SPECT)
scans, tests of the brain’s electrical activity (electroencephalographs or EEGs), or other tests. Several
types of oral and written tests are used to aid in the
AD diagnosis and to follow its progression, including
tests of mental status, functional abilities, memory,
and concentration. Still, the neurologic exam is
normal in most patients in early stages.
One of the most important parts of the diagnostic
process is to evaluate the patient for depression and
delirium, since each of these can be present with AD, or
may be mistaken for it. (Delirium involves a decreased
consciousness or awareness of one’s environment.)
144

Depression and memory loss both are common
in the elderly, and the combination of the often can
be mistaken for AD. On the other hand, depression
can be a risk factor for AD. A 2003 study showed that
a history of depressive symptoms can be associated
with nearly twice the risk of eventually developing
AD. Depression can be treated with drugs, although
some antidepressants can worsen dementia if it is
present, further complicating both diagnosis and
treatment.
An early and accurate diagnosis of AD is important in developing strategies for managing symptoms
and for helping patients and their families planning
for the future and pursuing care options while the
patient can still take part in the decision-making
process.
A genetic test for the APOE e4 gene is available,
but is not used for diagnosis, since possessing even two
copies does not ensure that a person will develop AD.
In addition, access to genetic information could affect
the insurability of a patient if disclosed, and also affect
employment status and legal rights.

Treatment
Alzheimer’s disease is presently incurable. Recent
reports show that prompt intervention can slow decline
from AD. The use of medications mentioned below as
early as possible in the course of AD can help people
with the disease maintain independent function as long
as possible. The remaining treatment for a person with
AD is good nursing care, providing both physical and
emotional support for a person who is gradually able to
do less and less for himself, and whose behavior is
becoming more and more erratic. Modifications of the
home to increase safety and security often are necessary. The caregiver also needs support to prevent anger,
despair, and burnout from becoming overwhelming.
Becoming familiar with the issues likely to lie ahead,
and considering the appropriate financial and legal
issues early on, can help both the patient and family
cope with the difficult process of the disease. Regular
medical care by a practitioner with a non-defeatist
attitude toward AD is important so that illnesses such
as urinary or respiratory infections can be diagnosed
and treated properly, rather than being incorrectly
attributed to the inevitable decline seen in AD.
People with AD often are depressed or anxious,
and may suffer from sleeplessness, poor nutrition, and
general poor health. Each of these conditions is treatable to some degree. It is important for the person
with AD to eat well and continue to exercise.
Professional advice from a nutritionist may be useful
GALE ENCYCLOPEDIA OF MEDICINE

Drugs
As of 2003, four drugs—tacrine (Cognex), donepezil hydrochloride (Aricept), and rivastigmine
(Exelon)—have been approved by the FDA for its
treatment. Tacrine has been shown to be effective for
improving memory skills, but only in patients with
mild-to-moderate AD, and even then in less than half
of those who take it. Its beneficial effects are usually
mild and temporary, but it may delay the need for
nursing home admission. The most significant side
effect is an increase in a liver enzyme known as alanine
aminotransferase, or ALT. Patients taking tacrine
must have a weekly blood test to monitor their ALT
levels. Other frequent side effects include nausea,
vomiting, diarrhea, abdominal pain, indigestion, and
skin rash. The cost of tacrine was about $125 per
month in early 1998, with additional costs for the
weekly blood monitoring. Despite its high cost, tacrine
appears to be cost-effective for those who respond to
it, since it may decrease the number of months a
patient needs nursing care. Donepezil is the drug
most commonly used to treat mild to moderate symptoms of AD, although it only helps some patients for
periods of time ranging from months to about two
years. Donepezil has two advantages over tacrine: it
has fewer side effects, and it can be given once daily
rather than three times daily. Donepezil does not
appear to affect liver enzymes, and therefore does
not require weekly blood tests. The frequency of
abdominal side effects is also lower. The monthly
cost is approximately the same. Rivastigmine,
approved for use in April of 2000, has been shown to
improve the ability of patients to carry out daily activities, such as eating and dressing, decrease behavioral
symptoms such as delusions and agitation, and improve
cognitive functions such as thinking, memory, and
speaking. The cost is similar to those of the other
two drugs. However, none of these three drugs stops
or reverses the progression of AD. Galantamine
(Reminyl) works in the early and moderates stages
of AD. It has fewer side effects than other drugs,
with the exception of donepezil and must be taken
GALE ENCYCLOPEDIA OF MEDICINE

twice a day. Three other drugs were being tested for
AD treatment in mid-2003.
Estrogen, the female sex hormone, is widely prescribed for post-menopausal women to prevent osteoporosis. Studies once showed that estrogen was
beneficial to women with AD, but in 2003, a large
clinical trial called the Women’s Health Initiative
showed dementia among other negative effects of
combined estrogen therapy.
Preliminary studies once suggested a reduced risk
for developing AD in elderly people who regularly used
nonsteroidal anti-inflammatory drugs (NSAIDs),
including aspirin, ibuprofen, and naproxen, although
not acetaminophen. However, an important study
published in 2003 showed that NSAIDs were not effective in preventing or slowing the progression of AD.
The study authors recommended that people stop
taking NSAIDs to slow dementia.
Antioxidants, which act to inhibit and protect
against oxidative damage caused by free radicals, have
been shown to inhibit toxic effects of beta-amyloid in
tissue culture. Therefore, research is being conducted
to see whether antioxidants may delay or prevent AD.
Another antioxidant, vitamin E, is also thought
to delay AD onset. Hoever, it is not yet clear whether
this is due to the specific action of vitamin E on brain
cells, or to an increase in the overall health of those
taking it.
Drugs such as antidepressants, anti-psychotics,
and sedatives are used to treat the behavioral symptoms (agitation, aggression, wandering, and sleep disorders) of AD. Research is being conducted to search
for better treatments, including non-drug approaches
for AD patients.
Nursing care and safety
The person with Alzheimer’s disease will gradually lose the ability to dress, groom, feed, bathe, or use
the toilet by himself; in the later stages of the disease,
he may be unable to move or speak. In addition, the
person’s behavior becomes increasingly erratic. A
tendency to wander may make it difficult to leave
him unattended for even a few minutes and make
even the home a potentially dangerous place. In
addition, some people with AD may exhibit inappropriate sexual behaviors.
The nursing care required for a person with AD is
well within the abilities of most people to learn. The
difficulty for many caregivers comes in the constant
but unpredictable nature of the demands put on them.
In addition, the personality changes undergone by a
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Alzheimer’s disease

to provide healthy, easy-to-prepare meals. Finger
foods may be preferable to those requiring utensils to
be eaten. Regular exercise (supervised if necessary for
safety) promotes overall health. A calm, structured
environment with simple orientation aids (such as
calendars and clocks) may reduce anxiety and increase
safety. Other psychiatric symptoms, such as depression, anxiety, hallucinations (seeing or hearing things
that aren’t there), and delusions (false beliefs) may be
treated with drugs if necessary.

Alzheimer’s disease

person with AD can be heartbreaking for family members as a loved one deteriorates, seeming to become a
different person. Not all people with AD develop
negative behaviors. Some become quite gentle, and
spend increasing amounts of time in dreamlike states.
A loss of good grooming may be one of the early
symptoms of AD. Mismatched clothing, unkempt hair,
and decreased interest in personal hygiene become
more common. Caregivers, especially spouses, may
find these changes socially embarrassing and difficult
to cope with. The caregiver usually will need to spend
increasing amounts of time on grooming to compensate
for the loss of attention from the patient, although
some adjustment of expectations (while maintaining
cleanliness) is often needed as the disease progresses.
Proper nutrition is important for a person with
AD, and may require assisted feeding early on, to
make sure the person is taking in enough nutrients.
Later on, as movement and swallowing become difficult, a feeding tube may be placed into the stomach
through the abdominal wall. A feeding tube requires
more attention, but is generally easy to care for if the
patient is not resistant to its use.
For many caregivers, incontinence becomes the
most difficult problem to deal with at home, and is a
principal reason for pursuing nursing home care. In
the early stages, limiting fluid intake and increasing
the frequency of toileting can help. Careful attention
to hygiene is important to prevent skin irritation and
infection from soiled clothing.
Persons with dementia must deal with six basic
safety concerns: injury from falls, injury from ingesting dangerous substances, leaving the home and getting lost, injury to self or others from sharp objects,
fire or burns, and the inability to respond rapidly to
crisis situations. In all cases, a person diagnosed with
AD should no longer be allowed to drive, because of
the increased potential for accidents and the increased
likelihood of wandering very far from home while
disoriented. In the home, simple measures such as
grab bars in the bathroom, bed rails on the bed, and
easily negotiable passageways can greatly increase
safety. Electrical appliances should be unplugged and
put away when not in use, and matches, lighters, knives, or weapons should be stored safely out of reach.
The hot water heater temperature may be set lower
to prevent accidental scalding. A list of emergency
numbers, including the poison control center and the
hospital emergency room, should be posted by the
phone. As the disease progresses, caregivers need to
periodically reevaluate the physical safety of the home
and introduce new strategies for continued safety.
146

Care for the caregiver
Family members or others caring for a person with
AD have an extremely difficult and stressful job, which
becomes harder as the disease progresses. Dementia
caregivers spend significantly more time on caregiving
than do people providing care for those with other
types of illnesses. This type of caregiving also has a
greater impact in terms of employment complications,
caregiver strain, mental and physical health problems,
time for leisure and other family members, and family
conflict than do other types of caregiving. It is common
for AD caregivers to develop feelings of anger, resentment, guilt, and hopelessness, in addition to the sorrow
they feel for their loved one and for themselves.
Depression is an extremely common consequence of
being a full-time caregiver for a person with AD.
Support groups are an important way to deal with the
stress of caregiving. Becoming a member of an AD
caregivers’ support group can be one of the most
important things a family member does, not only for
him or herself, but for the person with AD as well. The
location and contact numbers for AD caregiver support groups are available from the Alzheimer’s
Association; they also may be available through a
local social service agency, the patient’s physician, or
pharmaceutical companies that manufacture the drugs
used to treat AD. Medical treatment for depression
may be an important adjunct to group support.
Outside help, nursing homes, and governmental
assistance
Most families eventually need outside help to
relieve some of the burden of around-the-clock care
for a person with AD. Personal care assistants, either
volunteer or paid, may be available through local social
service agencies. Adult daycare facilities are becoming
increasingly common. Meal delivery, shopping assistance, or respite care may be available as well.
Providing the total care required by a person
with late-stage AD can become an overwhelming
burden for a family, even with outside help. At this
stage, many families consider nursing home care.
This decision often is one of the most difficult for
the family, since it is often seen as an abandonment of
the loved one and a failure of the family. Careful
counseling with a sympathetic physician, clergy, or
other trusted adviser may ease the difficulties of this
transition. Selecting a nursing home may require a
difficult balancing of cost, services, location, and
availability. Keeping the entire family involved in
the decision may help prevent further stress from
developing later on.
GALE ENCYCLOPEDIA OF MEDICINE

Private long-term care insurance, special ‘‘reverse
mortgages,’’ viatical insurance, and other financial
devices are other ways of paying for care for those
with the appropriate financial situations. Further
information on these options may be available
through resources listed below.

Alternative treatment
Several substances are currently being tested
for their ability to slow the progress of Alzheimer’s
disease. These include acetylcarnitine, a supplement
that acts on the cellular energy structures known as
mitochondria. Ginkgo extract, derived from the leaves
of the Ginkgo biloba tree, appears to have antioxidant
as well as anti-inflammatory and anticoagulant properties. Ginkgo extract has been used for many years
in China and is widely prescribed in Europe for treatment of circulatory problems. A 1997 study of patients
with dementia seemed to show that ginkgo extract
could improve their symptoms, though the study was
criticized for certain flaws in its method. Large scale
follow-up studies are being conducted to determine
whether Ginkgo extract can prevent or delay the
development of AD. Ginkgo extract is available in
many health food or nutritional supplement stores.
Some alternative practitioners also advise people
with AD to take supplements of phosphatidylcholine,
vitamin B12, gotu kola, ginseng, St. Johnõs Wort,
rosemary, saiko-keishi-to-shakuyaku (A Japanese
herbal mixture), and folic acid.

Prognosis
While Alzheimer’s disease may not be the direct
cause of death, the generally poorer health of a person
with AD increases the risk of life-threatening infection, including pneumonia. In addition, other diseases
common in old age–cancer, stroke, and heart disease–
may lead to more severe consequences in a person with
AD. On average, people with AD live eight years past
their diagnosis, with a range from one to 20 years.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Currently, there is no sure way to prevent
Alzheimer’s disease. treatments discussed above may
eventually be proven to reduce the risk of developing
the disease. Avoiding risks such as hormone replacement therapy may help prevent development of AD.
Research on the prevention of AD is focusing on
blocking the production of amyloid in the brain as well
as breaking down beta-amyloid once it is released
from cells but before it has a chance to aggregate
into insoluble plaques. There also are promising
studies being conducted to develop an AD vaccine,
where immune responses may result in the elimination
of the formation of amyloid plaques.
The Alzheimer’s Disease Research Centers
(ADCs) program promotes research, training and
education, technology transfer, and multicenter and
cooperative studies in AD, other dementias, and normal brain aging. Each ADC enrolls and performs
studies on AD patients and healthy older people.
Persons can participate in research protocols and
clinical drug trials at these centers. Data from the
ADCs as well as from other sources are coordinated
and made available for use by researchers at the
National Alzheimer’s Coordinating Center, established in 1999.
Resources
BOOKS

Cohen, Donna, and Carl Eisdorfer. The Loss of Self: A
Family Resource for the Care of Alzheimer’s Disease and
Related Disorders. Revised. NewYork: W.W. Norton &
Company, 2001.
Geldmacher, David S. Contemporary Diagnosis and
Management ofAlzheimer’s Disease. Newtown,
PA: Associates in Medical Marketing Co., Inc.,
2001.
Gruetzner, Howard. Alzheimer’s: A Caregiverõs Guideand
Sourcebook. 3rd ed. New York: John Wiley & Sons,
2001.
Mace, Nancy L., and Peter V. Rabins. The 36-Hour Day: A
Family Guide for Caring with Persons with Alzheimer
Disease, Related Dementing Illnesses, and MemoryLoss
in Later Life. New York: Warner Books, 2001.
Teitel, Rosette, and Marc L. Gordon. The Handholderõs
Handbook: A Guide for Caregivers of Alzheimerõs and
other Dementias. NewBrunswick, NJ: Rutgers
University Press, 2001.
PERIODICALS

‘‘Alzheimer’s Could be Linked to Depression.’’ GP (May 26,
2003): 4.
‘‘Alzheimer’s Could Reduced by Education.’’ The Lancet
(June 28, 2003): 2215.
147

Alzheimer’s disease

Several federal government programs may ease the
cost of caring for a person with AD, including Social
Security Disability, Medicare, and Supplemental
Security Income. Each of these programs may provide
some assistance for care, medication, or other costs,
but none of them will pay for nursing home care indefinitely. Medicaid is a state-funded program that may
provide for some or all of the cost of nursing home care,
although there are important restrictions. Details of
the benefits and eligibility requirements of these programs are available through the local Social Security
or Medicaid office, or from local social service agencies.

Amblyopia

‘‘Contrary to Some Earlier Results, New Study Shows
NSAIDs Do Not Slow Progression of Alzheimer’s
Disease.’’ The Brown University Geriatric
Psychopharmacology Update (July 2003): 1.
Gitlin, L.N., and M. Corcoran. ‘‘Making Homes Safer:
Environmental Adaptations for People with
Dementia.’’ Alzheimer’s Care Quarterly 1 (2000): 50-58.
Helmuth, L. ‘‘Alzheimer’s Congress: Further Progress on aBAmyloid Vaccine.’’ Science 289, no. 5476 (2000): 375.
Josefson, Deborah. ‘‘Latests HRT Trial Results Show Risk
of Dementia.’’ British Medical Journal (June 7, 2003):
1232.
McReady, Norah. ‘‘Prompt Intervention May Slow
Alzheimer’s Decline.’’ Family Practice News (May 1,
2003): 32-41.
Naditz, Alan. ‘‘Deeply Affected: As the Nation Ages,
Alzheimer’s Will Strike More People Close to Us.’’
Contemporary Long Term Care (July 2003): 20-23.
‘‘Researchers Believe ‘‘Silent’’ Strokes Boost Risk.’’ GP
(April 14, 2003): 9.
OTHER

Alzheimer’s Disease Books and Videotapes. <http://
www.alzheimersbooks.com>.
National Institute on Aging, National Institutes of Health.
2000: Progress Report on Alzheimer’s Disease - Taking
the Next Steps. NIH Publication No. 4859 (2000).
<http://www.alzheimers.org/pubs/
prog00.htm#References>.

Judith Sims
Teresa G. Odle

Description
Lazy eye is a common non-medical term used to
describe amblyopia because the eye with poorer vision
doesn’t seem to be doing its job of seeing. Amblyopia
is the most common cause of impaired vision in children, affecting nearly three out of every 100 people or
2-4% of the population. Vision is a combination of the
clarity of the images of the eyes (visual acuity) and the
processing of those images by the brain. If the images
produced by the two eyes are substantially different,
the brain may not be able to fuse the images. Instead of
seeing two different images or double vision (diplopia), the brain suppresses the blurrier image. This
suppression can lead to amblyopia. During the first
few years of life, preferring one eye over the other may
lead to poor visual development in the blurrier eye.

Causes and symptoms
Some of the major causes of amblyopia are as
follows:


Strabismus. A misalignment of the eyes (strabismus)
is the most common cause of functional amblyopia.
The two eyes are looking in two different directions at
the same time. The brain is sent two different images
and this causes confusion. Images from the misaligned
or ‘‘crossed’’ eye are turned off to avoid double vision.



Anisometropia. This is another type of functional
amblyopia. In this case, there is a difference of refractive states between the two eyes (in other words, a
difference of prescriptions between the two eyes).
For example, one eye may be more nearsighted than
the other eye, or one eye may be farsighted and the
other eye nearsighted. Because the brain cannot fuse
the two dissimilar images, the brain will suppress the
blurrier image, causing the eye to become amblyopic.



Cataract. Clouding of the lens of the eye will cause
the image to be blurrier than the other eye. The brain
‘‘prefers’’ the clearer image. The eye with the cataract
may become amblyopic.



Ptosis. This is the drooping of the upper eyelid. If
light cannot enter the eye because of the drooping lid,
the eye is essentially not being used. This can lead to
amblyopia.



Nutrition. A type of organic amblyopia in which
nutritional deficiencies or chemical toxicity may
result in amblyopia. Alcohol, tobacco, or a deficiency
in the B vitamins may result in toxic amblyopia.



Heredity. Amblyopia can run in families.

Ambiguous genitals see Intersex states

I Amblyopia
Definition
Amblyopia is an uncorrectable decrease in vision in
one or both eyes with no apparent structural abnormality seen to explain it. It is a diagnosis of exclusion,
meaning that when a decrease in vision is detected,
other causes must be ruled out. Once no other cause is
found, amblyopia is the diagnosis. Generally, a difference of two lines or more (on an eye-chart test of visual
acuity) between the two eyes or a best corrected vision
of 20/30 or worse would be defined as amblyopia. For
example, if someone has 20/20 vision with the right eye
and only 20/40 with the left, and the left eye cannot
achieve better vision with corrective lenses, the left eye
is said to be amblyopic.
148

Barring the presence of strabismus or ptosis,
children may or may not show signs of amblyopia.
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Anisometropia—An eye condition in which there
is an inequality of vision between the two eyes.
There may be unequal amounts of nearsightedness,
farsightedness, or astigmatism, so that one eye will
be in focus while the other will not.
Cataract—Cloudiness of the eye’s natural lens.
Occulsion therapy—A type of treatment for
amblyopia in which the good eye is patched for a
period of time. This forces the weaker eye to be
used.
Man with a lazy eye. (Custom Medical Stock Photo. Reproduced
by permission.)

Children may hold their heads at an angle while trying
to favor the eye with normal vision. They may have
trouble seeing or reaching for things when approached
from the side of the amblyopic eye. Parents should
see if one side of approach is preferred by the child
or infant. If an infant’s good eye is covered, the child
may cry.

Diagnosis
Because children with outwardly normal eyes may
have amblyopia, it is important to have regular vision
screenings performed for all children. While there is
some controversy regarding the age children should
have their first vision examination, their eyes can, in
actuality, be examined at any age, even at one day of life.
Some recommend that children have their vision
checked by their pediatrician, family physician,
ophthalmologist, or optometrist at or before six
months of age. Others recommend testing by at least
the child’s fourth birthday. There may be a ‘‘critical
period’’ in the development of vision, and amblyopia
may not be treatable after age eight or nine. The earlier
amblyopia is found, the better the possible outcome.
Most physicians test vision as part of a child’s medical
examination. If there is any sign of an eye problem,
they may refer a child to an eye specialist.
There are objective methods, such as retinoscopy,
to measure the refractive status of the eyes. This can
help determine anisometropia. In retinoscopy, a handheld instrument is used to shine a light in the child’s (or
infant’s) eyes. Using hand-held lenses, a rough prescription can be obtained. Visual acuity can be determined using a variety of methods. Many different eye
charts are available (e.g., tumbling E, pictures, or
letters). In amblyopia, single letters are easier to
GALE ENCYCLOPEDIA OF MEDICINE

Strabismus—A condition in which the eyes are
misaligned and point in different directions. One
eye may look straight ahead, while the other turns
inward, outward, upward, or downward. This is
also called crossed-eyes.
Visual acuity—Acuity is the acuteness or sharpness
of vision.

recognize than when a whole line is shown. This is
called the ‘‘crowding effect’’ and helps in diagnosing
amblyopia. Neutral density filters may also be held
over the eye to aid in the diagnosis. Sometimes visual
fields to determine defects in the area of vision will be
performed. Color vision testing may also be performed. Again, it must be emphasized that amblyopia
is a diagnosis of exclusion. Visual or life-threatening
problems can also cause a decrease in vision. An examination of the eyes and visual system is very important
when there is an unexplained decrease in vision.

Treatment
The primary treatment for amblyopia is occlusion
therapy. It is important to alternate patching the good
eye (forcing the amblyopic eye to work) and the
amblyopic eye. If the good eye is constantly patched,
it too may become amblyopic because of disuse. The
treatment plan should be discussed with the doctor to
fully understand how long the patch will be on. When
patched, eye exercises may be prescribed to force the
amblyopic eye to focus and work. This is called vision
therapy or vision training (eye exercises). Even after
vision has been restored in the weak eye, part-time
patching may be required over a period of years to
maintain the improvement.
While patching is necessary to get the amblyopic
eye to work, it is just as important to correct the reason
for the amblyopia. Glasses may also be worn if there
149

Amblyopia

KEY TERMS

Amebiasis

are errors in refraction. Surgery or vision training may
be necessary in the case of strabismus. Better nutrition
is indicated in some toxic amblyopias. Occasionally,
amblyopia is treated by blurring the vision in the good
eye with eye drops or lenses to force the child to use the
amblyopic eye.

Prognosis
The younger the person, the better the chance for
improvement with occlusion and vision therapy.
However, treatment may be successful in older children–even adults. Success in the treatment of amblyopia also depends upon how severe the amblyopia is,
the specific type of amblyopia, and patient compliance. It is important to diagnose and treat amblyopia
early because significant vision loss can occur if left
untreated. The best outcomes result from early diagnosis and treatment.

Prevention
To protect their child’s vision, parents must be
aware of amblyopia as a potential problem. This
awareness may encourage parents to take young children for vision exams early on in life–certainly before
school age. Proper nutrition is important in the avoidance of toxic amblyopia.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.

Lorraine Steefel, RN

I Amebiasis
Definition
Amebiasis is an infectious disease caused by a
parasitic one-celled microorganism (protozoan) called
Entamoeba histolytica. Persons with amebiasis may
experience a wide range of symptoms, including diarrhea, fever, and cramps. The disease may also affect
the intestines, liver, or other parts of the body.
150

Description
Amebiasis, also known as amebic dysentery, is one
of the most common parasitic diseases occurring in
humans, with an estimated 500 million new cases each
year. It occurs most frequently in tropical and subtropical areas where living conditions are crowded, with
inadequate sanitation. Although most cases of amebiasis occur in persons who carry the disease but do
not exhibit any symptoms (asymptomatic), as many as
100,000 people die of amebiasis each year. In the
United States, between 1 and 5% of the general population will develop amebiasis in any given year, while
male homosexuals, migrant workers, institutionalized
people, and recent immigrants develop amebiasis at a
higher rate.
Human beings are the only known host of the
amebiasis organism, and all groups of people, regardless
of age or sex, can become affected. Amebiasis is primarily spread in food and water that has been contaminated
by human feces but is also spread by person-to-person
contact. The number of cases is typically limited, but
regional outbreaks can occur in areas where human
feces are used as fertilizer for crops, or in cities with
water supplies contaminated with human feces.

Causes and symptoms
Recently, it has been discovered that persons
with symptom-causing amebiasis are infected with
Entamoeba histolytica, and those individuals who
exhibit no symptoms are actually infected with an
almost identical-looking ameba called Entamoeba
dispar. During their life cycles, the amebas exist in
two very different forms: the infective cyst or
capsuled form, which cannot move but can survive
outside the human body because of its protective
covering, and the disease-producing form, the
trophozoite, which although capable of moving, cannot survive once excreted in the feces and, therefore,
cannot infect others. The disease is most commonly
transmitted when a person eats food or drinks water
containing E. histolytica cysts from human feces. In
the digestive tract the cysts are transported to the
intestine where the walls of the cysts are broken
open by digestive secretions, releasing the mobile
trophozoites. Once released within the intestine, the
trophozoites multiply by feeding on intestinal bacteria or by invading the lining of the large intestine.
Within the lining of the large intestine, the
trophozoites secrete a substance that destroys intestinal tissue and creates a distinctive bottle-shaped
sore (ulcer). The trophozoites may remain inside the
intestine, in the intestinal wall, or may break through
GALE ENCYCLOPEDIA OF MEDICINE

Ameboma—A mass of tissue that can develop on
the wall of the colon in response to amebic
infection.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Appendicitis—Condition characterized by the
rapid inflammation of the appendix, a part of the
intestine.
A micrograph of Entameoba histolytica, a parasitic amoeba
which invades and destroys the tissues of the intestines,
causing amebiasis and ulceration to the intestinal wall.
(Photo Researchers, Inc. Reproduced by permission.)

the intestinal wall and be carried by the blood to the
liver, lungs, brain, or other organs. Trophozoites that
remain in the intestines eventually form new cysts
that are carried through the digestive tract and
excreted in the feces. Under favorable temperature
and humidity conditions, the cysts can survive in
soil or water for weeks to months, ready to begin
the cycle again.
Although 90% of cases of amebiasis in the United
States are mild, pregnant women, children under two
years of age, the elderly, malnourished individuals,
and people whose immune systems may be compressed,
such as cancer or AIDS patients and those individuals
taking prescription medications that suppress the
immune system, are at a greater risk for developing a
severe infection.
The signs and symptoms of amebiasis vary
according to the location and severity of the infection
and are classified as follows:
Intestinal amebiasis
Intestinal amebiasis can be subdivided into several
categories:
ASYMPTOMATIC INFECTION. Most persons with
amebiasis have no noticeable symptoms. Even though
these individuals may not feel ill, they are still capable
of infecting others by person-to-person contact or by
contaminating food or water with cysts that others
may ingest, for example, by preparing food with
unwashed hands.
CHRONIC NON-DYSENTERIC INFECTION. Individuals may experience symptoms over a long period
of time during a chronic amebiasis infection and

GALE ENCYCLOPEDIA OF MEDICINE

Asymptomatic—Persons who carry a disease and
are usually capable of transmitting the disease but
who do not exhibit symptoms of the disease are
said to be asymptomatic.
Dysentery—Intestinal infection marked by diarrhea containing blood and mucus.
Fulminating colitis—A potentially fatal complication of amebic dysentery marked by sudden and
severe inflammation of the intestinal lining, severe
bleeding or hemorrhaging, and massive shedding
of dead tissue.
Inflammatory bowel disease (IBD)—Disease in
which the lining of the intestine becomes inflamed.
Lumen—The inner cavity or canal of a tube-shaped
organ, such as the bowel.
Protozoan—A single-celled, usually microscopic
organism that is eukaryotic and, therefore, different
from bacteria (prokaryotic).

experience recurrent episodes of diarrhea that last
from one to four weeks and recur over a period of
years. These patients may also suffer from abdominal
cramps, fatigue, and weight loss.
AMEBIC DYSENTERY. In severe cases of intestinal
amebiasis, the organism invades the lining of the
intestine, producing sores (ulcers), bloody diarrhea,
severe abdominal cramps, vomiting, chills, and
fevers as high as 104-1058F (40-40.68C). In addition,
a case of acute amebic dysentery may cause complications, including inflammation of the appendix
(appendicitis), a tear in the intestinal wall (perforation), or a sudden, severe inflammation of the colon
(fulminating colitis).
AMEBOMA. An ameboma is a mass of tissue in the
bowel that is formed by the amebiasis organism. It can
result from either chronic intestinal infection or acute
amebic dysentery. Amebomas may produce symptoms that mimic cancer or other intestinal diseases.

151

Amebiasis

KEY TERMS

Amebiasis

PERIANAL ULCERS. Intestinal amebiasis may produce skin infections in the area around the patient’s
anus (perianal). These ulcerated areas have a
‘‘punched-out’’ appearance and are painful to the touch.

Extraintestinal amebiasis
Extraintestinal amebiasis accounts for approximately 10% of all reported amebiasis cases and includes
all forms of the disease that affect other organs.
The most common form of extraintestinal amebiasis is amebic abscess of the liver. In the United States,
amebic liver abscesses occur most frequently in young
Hispanic adults. An amebic liver abscess can result
from direct infection of the liver by E. histolytica or as
a complication of intestinal amebiasis. Patients with an
amebic abscess of the liver complain of pain in the chest
or abdomen, fever, nausea, and tenderness on the right
side directly above the liver.
Other forms of extraintestinal amebiasis, though
rare, include infections of the lungs, chest cavity,
brain, or genitals. These are extremely serious and
have a relatively high mortality rate.

Diagnosis
Diagnosis of amebiasis is complicated, partly
because the disease can affect several areas of the
body and can range from exhibiting few, if any, symptoms to being severe, or even life-threatening. In most
cases, a physician will consider a diagnosis of amebiasis when a patient has a combination of symptoms, in
particular, diarrhea and a possible history of recent
exposure to amebiasis through travel, contact with
infected persons, or anal intercourse.
It is vital to distinguish between amebiasis and
another disease, inflammatory bowel disease (IBD)
that produces similar symptoms because, if diagnosed
incorrectly, drugs that are given to treat IBD can
encourage the growth and spread of the amebiasis
organism. Because of the serious consequences of
misdiagnosis, potential cases of IBD must be confirmed with multiple stool samples and blood tests,
and a procedure involving a visual inspection of the
intestinal wall using a thin lighted, tubular instrument
(sigmoidoscopy) to rule out amebiasis.
A diagnosis of amebiasis may be confirmed by one
or more tests, depending on the location of the disease.
Stool examination
This test involves microscopically examining a
stool sample for the presence of cysts and/or trophozoites of E. histolytica and not one of the many other
152

intestinal amebas that are often found but that do not
cause disease. A series of three stool tests is approximately 90% accurate in confirming a diagnosis of
amebic dysentery. Unfortunately, however, the stool
test is not useful in diagnosing amebomas or extraintestinal infections.
Sigmoidoscopy
Sigmoidoscopy is a useful diagnostic procedure in
which a thin, flexible, lighted instrument, called a
sigmoidoscope, is used to visually examine the lower
part of the large intestine for amebic ulcers and take
tissue or fluid samples from the intestinal lining.
Blood tests
Although tests designed to detect a specific
protein produced in response to amebiasis infection
(antibody) are capable of detecting only about 10%
of cases of mild amebiasis, these tests are extremely
useful in confirming 95% of dysentery diagnoses
and 98% of liver abscess diagnoses. Blood serum will
usually test positive for antibody within a week of
symptom onset. Blood testing, however, cannot
always distinguish between a current or past infection
since the antibodies may be detectable in the blood
for as long as 10 years following initial infection.
Imaging studies
A number of sophisticated imaging techniques,
such as computed tomography scans (CT), magnetic
resonance imaging (MRI), and ultrasound, can be
used to determine whether a liver abscess is present.
Once located, a physician may then use a fine needle
to withdraw a sample of tissue to determine whether
the abscess is indeed caused by an amebic infection.

Treatment
Asymptomatic or mild cases of amebiasis may
require no treatment. However, because of the
potential for disease spread, amebiasis is generally
treated with a medication to kill the disease-causing
amebas. More severe cases of amebic dysentery are
additionally treated by replacing lost fluid and
blood. Patients with an amebic liver abscess will
also require hospitalization and bed rest. For those
cases of extraintestinal amebiasis, treatment can be
complicated because different drugs may be required
to eliminate the parasite, based on the location of
the infection within the body. Drugs used to treat
amebiasis, called amebicides, are divided into two
categories:
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These drugs get their name because they act on
organisms within the inner cavity (lumen) of the
bowel. They include diloxanide furoate, iodoquinol,
metronidazole, and paromomycin.
Tissue amebicides
Tissue amebicides are used to treat infections in
the liver and other body tissues and include emetine,
dehydroemetine, metronidazole, and chloroquine.
Because these drugs have potentially serious side
effects, patients given emetine or dehydroemetine
require bed rest and heart monitoring. Chloroquine
has been found to be the most useful drug for treating
amebic liver abscess. Patients taking metronidazole
must avoid alcohol because the drug-alcohol combination causes nausea, vomiting, and headache.
Most patients are given a combination of luminal
and tissue amebicides over a treatment period of seven
to ten days. Follow-up care includes periodic stool
examinations beginning two to four weeks after the
end of medication treatment to check the effectiveness
of drug therapy.

Prognosis
The prognosis depends on the location of the
infection and the patient’s general health prior to
infection. The prognosis is generally good, although
the mortality rate is higher for patients with ameboma,
perforation of the bowel, and liver infection. Patients
who develop fulminant colitis have the most serious
prognosis, with over 50% mortality.

Prevention
There are no immunization procedures or medications that can be taken prior to potential exposure to
prevent amebiasis. Moreover, people who have had
the disease can become reinfected. Prevention requires
effective personal and community hygiene.
Specific safeguards include the following:


Purification of drinking water. Water can be purified
by filtering, boiling, or treatment with iodine.



Proper food handling. Measures include protecting
food from contamination by flies, cooking food
properly, washing one’s hands after using the bathroom and before cooking or eating, and avoiding
foods that cannot be cooked or peeled when traveling in countries with high rates of amebiasis.



Careful disposal of human feces.

GALE ENCYCLOPEDIA OF MEDICINE



Monitoring the contacts of amebiasis patients. The
stools of family members and sexual partners of
infected persons should be tested for the presence of
cysts or trophozoites.

Resources
BOOKS

Friedman, Lawrence S. ‘‘Liver, Biliary Tract, & Pancreas.’’
In Current Medical Diagnosis and Treatment, 1998,
edited by Stephen McPhee, et al., 37th ed. Stamford:
Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Amebic dysentery see Amebiasis

I Amenorrhea
Definition
The absence of menstrual periods is called amenorrhea. Primary amenorrhea is the failure to start
having a period by the age of 16. Secondary amenorrhea is more common and refers to either the temporary or permanent ending of periods in a woman who
has menstruated normally in the past. Many women
miss a period occasionally. Amenorrhea occurs if a
woman misses three or more periods in a row.

Description
The absence of menstrual periods is a symptom,
not a disease. While the average age that menstruation
begins is 12, the range varies. The incidence of primary
amenorrhea in the United States is just 2.5%.
Some female athletes who participate in rowing,
long distance running, and cycling, may notice a few
missed periods. Women athletes at a particular risk for
developing amenorrhea include ballerinas and gymnasts, who typically exercise strenuously and eat poorly.

Causes and symptoms
Amenorrhea can have many causes. Primary amenorrhea can be the result of hormonal imbalances,
psychiatric disorders, eating disorders, malnutrition,
excessive thinness or fatness, rapid weight loss, body
fat content too low, and excessive physical conditioning. Intense physical training prior to puberty can delay
menarche (the onset of menstruation). Every year of
training can delay menarche for up to five months.
153

Amenorrhea

Luminal amebicides

Amenorrhea

KEY TERMS
Hymen—Membrane that stretches across the opening of the vagina.
Hypothyroidism—Underactive thyroid gland.
Hysterectomy—Surgical removal of the uterus.
Turner’s syndrome—A condition in which one
female sex chromosome is missing.

Some medications such as anti-depressants, tranquilizers, steroids, and heroin can induce amenorrhea.
Primary amenorrhea
However, the main cause is a delay in the beginning of puberty either from natural reasons (such as
heredity or poor nutrition) or because of a problem in
the endocrine system, such as a pituitary tumor or
hypothyroidism. An obstructed flow tract or inflammation in the uterus may be the presenting indications
of an underlying metabolic, endocrine, congenital or
gynecological disorder.
Typical causes of primary amenorrhea include:


excessive physical activity



drastic weight loss (such as occurs in anorexia or
bulimia)



extreme obesity



drugs (antidepressants or tranquilizers)



chronic illness



turner’s syndrome. (A chromosomal problem in place
at birth, relevant only in cases of primary amenorrhea)



the absence of a vagina or a uterus



imperforate hymen (lack of an opening to allow the
menstrual blood through)
Secondary amenorrhea

Some of the causes of primary amenorrhea can
also cause secondary amenorrhea – strenuous physical
activity, excessive weight loss, use of antidepressants
or tranquilizers, in particular. In adolescents, pregnancy and stress are two major causes. Missed periods
are usually caused in adolescents by stress and changes
in environment. Adolescents are especially prone to
irregular periods with fevers, weight loss, changes in
environment, or increased physical or athletic activity.
However, any cessation of periods for four months
should be evaluated.
154

The most common cause of seconardy amenorrhea is pregnancy. Also, a woman’s periods may halt
temporarily after she stops taking birth control pills.
This temporary halt usually lasts only for a month or
two, though in some cases it can last for a year or
more. Secondary amenorrhea may also be related to
hormonal problems related to stress, depression, anorexia nervosa or drugs, or it may be caused by any
condition affecting the ovaries, such as a tumor. The
cessation of menstruation also occurs permanently
after menopause or a hysterectomy.

Diagnosis
It may be difficult to find the cause of amenorrhea, but the exam should start with a pregnancy test;
pregnancy needs to be ruled out whenever a woman’s
period is two to three weeks overdue. Androgen
excess, estrogen deficiency, or other problems with
the endocrine system need to be checked. Prolactin in
the blood and the thyroid stimulating hormone (TSH)
should also be checked.
The diagnosis usually includes a patient history
and a physical exam (including a pelvic exam). If a
woman has missed three or more periods in a row, a
physician may recommend blood tests to measure
hormone levels, a scan of the skull to rule out the
possibility of a pituitary tumor, and ultrasound scans
of the abdomen and pelvis to rule out a tumor of the
adrenal gland or ovary.

Treatment
Treatment of amenorrhea depends on the cause.
Primary amenorrhea often requires no treatment, but
it’s alwaysimportant to discover the causeof the problem
in any case. Not all conditions can be treated, but any
underlying condition that is treatable should be treated.
If a hormonal imbalance is the problem, progesterone for one to two weeks every month or two may
correct the problem. With polycystic ovary syndrome,
birth control pills are often prescribed. A pituitary
tumor is treated with bromocriptine, a drug that reduces
certain hormone (prolactin) secretions. Weight loss may
bring on a period in an obese woman. Easing up on
excessive exercise and eating a proper diet may bring
on periods in teen athletes. In very rare cases, surgery
may be needed for women with ovarian or uterine cysts.

Prognosis
Prolonged amenorrhea can lead to infertility and
other medical problems such as osteoporosis (thinning
of the bones). If the halt in the normal period is caused
GALE ENCYCLOPEDIA OF MEDICINE

The prognosis for polycystic ovary disease
depends on the severity of the symptoms and the
treatment plan. Spironolactone, a drug that blocks
the production of male hormones, can help in reducing
body hair. If a woman wishes to become pregnant,
treatment with clomiphene may be required or, on
rare occasions, surgery on the ovaries.

Prevention
Primary amenorrhea caused by a congenital condition cannot be prevented. In general, however, women
should maintain a healthy diet, with plenty of exercise,
rest, and not too much stress, avoiding smoking and
substance abuse. Female athletes should be sure to eat a
balanced diet and rest and exercise normally. However,
many cases of amenorrhea cannot be prevented.
Resources
PERIODICALS

Hogg, Anne Cahill. ‘‘Breaking the Cycle: Often Confused
and Frustrated, Sufferers of Amenorrhea Now have
Better Treatment Options.’’ American Fitness 15, no. 4
(July-August 1997): 30-4.
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th St., S.W., P.O. Box 96920, Washington, DC
20090-6920. <http://www.acog.org>.
Federation of Feminist Women’s Health Centers.1469
Humboldt Rd, Suite 200, Chico, CA 96928. (530)
891-1911.
National Women’s Health Network. 514 10th St. NW, Suite
400, Washington, DC 20004. (202) 628-7814. <http://
www.womenshealthnetwork.org>.

Carol A. Turkington

Amikiacin see Aminoglycosides
Amiloride see Diuretics

acid disorders
I Amino
screening
Definition
Amino acid disorder screening checks for inherited
disorders in amino acid metabolism. Tests are most
GALE ENCYCLOPEDIA OF MEDICINE

commonly done on newborns. Two tests are available,
one using a blood sample and the other a urine sample.

Purpose
Amino acid disorder screening is done in newborns, and sometimes children and adults, to detect
inborn errors in metabolism of amino acids. Twenty of
the 100 known amino acids are the main building
blocks for human proteins. Proteins regulate every
aspect of cellular function. Of these 20 amino acids,
ten are not made by the body and must be acquired
through diet. Congenital (present at birth) enzyme deficiencies that affect amino acid metabolism or congenital
abnormalities in the amino acid transport system of
the kidneys creates a condition called aminoaciduria.
Screening is especially important in newborns.
Some congenital amino acid metabolic defects cause
mental retardation that can prevented with prompt
treatment of the newborn. One of the best known
examples of this is phenylketonuria (PKU). This is an
genetic error in metabolism of phenylalanine, an
amino acid found in milk. Individuals with PKU do
not produce the enzyme necessary to break down
phenylalanine.
PKU occurs in about one out of 16,000 live births
in the United States, but is more prevalent in caucasians and less prevalent in Ashkenazi Jews and African
Americans. Newborns in the United States are routinely screened for PKU by a blood test.
There are two types of aminoacidurias. Primary
or overflow aminoaciduria results from deficiencies in
the enzymes necessary to metabolize amino acids.
Overflow aminoaciduria is best detected by a blood
plasma test.
Secondary or renal aminoaciduria occurs because
of a congenital defect in the amino acid transport
system in the tubules of the kidneys. This produces
increased amino acids in the urine. Blood and urine
test in combination are used to determine if the aminoaciduria is of the overflow or renal type. Urine tests
are also used to monitor specific amino acid disorders.
Newborns are screened for amino acid disorders.
Young children with acidosis (accumulation of acid
in the body), severe vomiting and diarrhea, or urine
with an abnormal color or odor, are also screened
with a urine test for specific amino acid levels.

Precautions
Both blood and urine tests are simple tests that
can be done in a doctor’s office or clinic. These tests
can be done on even the youngest patients.
155

Amino acid disorders screening

by stress or illness, periods should begin again when
the stress passes or the illness is treated. Amenorrhea
that occurs with discontinuing birth control pills
usually go away within six to eight weeks, although it
may take up to a year.

Amino acid disorders screening

KEY TERMS
Amino acid—An organic compound composed of
both an amino group and an acidic carboxyl group;
amino acids are the basic building blocks of
proteins.
Aminoaciduria—The abnormal presence of amino
acids in the urine.
Chromatography—A family of laboratory techniques that separate mixtures of chemicals into their
individual components.
Enzyme—A biological catalyst that increases the
rate of a chemical reaction without being used up
in the reaction.
Metabolism—The sum of all the chemical and
energy reactions that take place in the human body.

Description
Two types of amino acid screening tests are used
together to diagnose amino acid disorders.
Blood plasma screening
In the blood test, a medical technician draws a
small amount of blood from a baby’s heel. The procedure is rapid and relatively painless. Total time for the
test is less than ten minutes. The blood is sent to a
laboratory where results will be available in about
two days.
Urine test
In the urine test, the patient is asked to urinate
into a collecting cup. For an infant, the urine is collected in a pediatric urine collector. The process is
painless. The length of time the test takes is determined
by how long it takes the patient to urinate. Results also
take about two days.
Both these tests use thin layer chromatography to
separate the amino acids present. Using this technique, the amino acids form a characteristic patterns on
a glass plate coated with a thin layer of silica gel. This
pattern is then compared to the normal pattern to
determine if there are abnormalities.

Preparation
Before the blood test, the patient must not eat or
drink for four hours. Failure to fast will alter the
results of the test.
156

The patient should eat and drink normally before
the urine test. Some drugs may affect the results of the
urine test. The technician handling the urine sample
should be informed of any medications the patient is
taking. Mothers of breastfeeding infants should report
any medications they are taking, since these can pass
from mother to child in breast milk.

Aftercare
The blood screening is normally done first.
Depending on the results, it is followed by the urine
test. It takes both tests to distinguish between overflow and renal aminoaciduria. Also, if the results are
abnormal, a 24-hour urine test is performed along
with other tests to determine the levels of specific
amino acids. In the event of abnormal results, there
are many other tests that will be performed to determine
the specific amino acid involved in the abnormality.

Risks
There are no particular risks associated with
either of these tests. Occasionally minor bruising may
occur at the site where the blood was taken.

Normal results
The pattern of amino acid banding on the thin
layer chromatography plates will be normal.

Abnormal results
The blood plasma amino acid pattern is abnormal in
overflow aminoaciduria and is normal in renal aminoaciduria. The pattern is abnormal in the urine test,
suggesting additional tests need to be done to determine
which amino acids are involved. In addition to PKU, a
variety of other amino acid metabolism disorders can
be detected by these tests, including tyrosinosis, histidinemia, maple syrup urine disease, hypervalinemia,
hyperprolinemia, and homocystinuria.
Resources
ORGANIZATIONS

Association for Neuro-Metabolic Disorders. 5223
Brookfield Lane, Sylvania, OH 43560-1809. (419)
885-1497.
Children’s PKU Network (CPN). 3790 Via De La Valle, Ste
120, Del Mar, CA 92014. (800) 377-6677. <http://
www.pkunetwork.org/>.
National Phenylketonuria Foundation. 6301 Tejas Drive,
Pasadena, TX 77503. (713) 487-4802.

Tish Davidson, A.M.
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Aminoglycosides are a group of antibiotics that
are used to treat certain bacterial infections. This
group of antibiotics includes at least eight drugs:
amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, and tobramycin.
All of these drugs have the same basic chemical
structure.

Purpose
Aminoglycosides are primarily used to combat
infections due to aerobic, Gram-negative bacteria.
These bacteria can be identified by their reaction to
Gram’s stain. In Gram’s staining, a film of material
containing the possible bacteria is placed on a glass
slide and dried. The slide is stained with crystal violet
for one minute, cleaned off with water and then placed
into a solution of Gram’s iodine solution for one
minute. The iodine solution is rinsed off and the slide
is immersed in 95% ethyl alcohol. The slide is then
stained again with reddish carbolfuchsin or safranine
for 30 seconds, rinsed in water, dried and examined.
Gram-positive bacteria retain the violet purple stain.
Gram-negative bacteria accept the red stain. Bacteria
that can successfully be combated with aminoglycosides include Pseudomonas, Acinetobacter, and
Enterobacter species, among others. Aminoglycosides
are also effective against mycobacteria, the bacteria
responsible for tuberculosis.
The aminoglycosides can be used against certain
Gram-positive bacteria, but are not typically
employed because other antibiotics are more effective
and have fewer side effects. Aminoglycosides are ineffective against anaerobic bacteria (bacteria that cannot grow in the presence of oxygen), viruses, and
fungi. And only one aminoglycoside, paromomycin,
is used against parasitic infection.
Like all other antibiotics, aminoglycosides are not
effective against influenza, the common cold, or other
viral infections.

Precautions
Pre-existing medical conditions–such as kidney
disease, eighth cranial nerve disease, myasthenia
gravis, and Parkinson’s disease–should be discussed
prior to taking any aminoglycosides. Pregnant
women are usually advised against taking aminoglycosides, because their infants may suffer damage to
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Aerobic bacteria—Bacteria which require oxygen
in order to grow and survive.
Anaerobic bacteria—Bacteria which cannot grow
or reproduce in the presence of oxygen.
Eighth cranial nerve disease—A disorder affecting
the eighth cranial nerve, characterized by a loss of
hearing and/or balance.
Gram-negative—Referring to a bacteria that take
on a pink color when exposed to Gram’s stain.
Gram-positive—Referring to a bacteria that takes
on a purplish- black color when exposed to Gram’s
stain.
Gram’s stain—A stain used in microbiology to classify bacteria and help identify the species to which
they belong. This identification aids in determining
treatment.
Kidney disease—Any disorder which impairs the
kidney’s ability to remove waste and toxins from
the body.
Myasthenis gravis—A neuromuscular disease
characterized by muscle weakness in the limbs
and face.
Parkinson’s disease—A neurological disorder
caused by deficiency of dopamine, a neurotransmitter, that is a chemical that assists in transmitting
messages between the nerves within the brain. It is
characterized by muscle tremor or palsy and rigid
movements.

their hearing, kidneys, or sense of balance. However,
those factors need to be considered alongside the
threat to the mother’s health and life in cases of
serious infection. Aminoglycosides do not pass into
breast milk to any great extent, so nursing mothers
may be prescribed aminoglycosides without injuring
their infants.

Description
Streptomycin, the first aminoglycoside, was
isolated from Streptomyces griseus in the mid-1940s.
This antibiotic was very effective against tuberculosis.
One of the main drawbacks to streptomycin is its
toxicity, especially to cells in the inner and middle ear
and the kidney. Furthermore, some strains of tuberculosis are resistant to treatment with streptomycin.
Therefore, medical researchers have put considerable
157

Aminoglycosides

I Aminoglycosides

Aminoglycosides

effort into identifying other antibiotics with streptomycin’s efficacy, but without its toxicity.
Aminoglycosides are absorbed very poorly from
the gastrointestinal tract; in fact, aminoglycosides
taken orally are excreted virtually unchanged and
undiminished in quantity. The route of drug administration depends on the type and location of the
infection being treated. The typical routes of administration are by intramuscular (injection into a muscle) or intravenous injection (injection into a vein),
irrigation, topical skin application, or inhalation.
If the infection being treated involves the central
nervous system, the drug can be injected into the
spinal canal.
The bactericidal ability of aminoglycosides has
not been fully explained. It is known that the drug
attaches to a bacterial cell wall and is drawn into the
cell via channels made up of the protein, porin. Once
inside the cell, the aminoglycoside attaches to the cell’s
ribosomes. Ribosomes are the intracellular structures
responsible for manufacturing proteins. This attachment either shuts down protein production or causes
the cell to produce abnormal, ineffective proteins. The
bacterial cell cannot survive with this impediment.
Antibiotic treatment using aminoglycosides may
pair the drug with a second type of antibiotic, usually
a beta-lactam or vancomycin, administered separately. Beta-lactams disrupt the integrity of the bacteria cell wall, making it more porous. The increased
porosity allows more of the aminoglycoside into the
bacteria cell.
Traditionally, aminoglycosides were administered
at even doses given throughout the day. It was thought
that a steady plasma concentration was necessary to
combat infection. However, this administration schedule is time and labor intensive. Furthermore, administering a single daily dose can be as effective, or more
effective, than several doses throughout the day.
Dosage depends on the patient’s age, weight, gender, and general health. Since the drug is cleared by the
kidneys, it is important to assess any underlying problems with kidney function. Kidney function is
assessed by measuring the blood levels of creatinine,
a protein normally found in the body. If these levels
are high, it is an indication that the kidneys may not be
functioning at an optimal rate and dosage will be
lowered accordingly.

Risks
Aminoglycosides have been shown to be toxic
to certain cells in the ears and in the kidneys.
158

Approximately 5-10% of the people who are
treated with aminoglycosides experience some side
effect, affecting their hearing, sense of balance, or
kidneys. However, in most cases the damage is minor
and reversible once medication is stopped.
If cells in the inner ear are damaged or destroyed,
an individual may experience a loss of balance and
feelings of dizziness. Damage to the middle ear may
result in hearing loss or tinnitus. Neomycin, kanamycin,
and amikacin are the most likely to cause problems with
hearing, and streptomycin and gentamicin carry the
greatest risk of causing vertigo and loss of balance.
Kidney damage, apparent with changes in urination
frequency or urine production, is most likely precipitated by neomycin, tobramycin, and gentamicin.
Young children and the elderly are at the greatest
risk of suffering side effects. Excessive dosage or poor
clearance of the drug from the body can be injurious at
any age.
Less common side effects include skin rashes and
itching. Very rarely, certain aminoglycosides may
cause difficulty in breathing, weakness, or drowsiness.
Gentamicin, when injected, may cause leg cramps,
skin rash, fever, or seizures.
If side effects linger or become worse after medication is stopped, it is advisable to seek medical advice.
Side effects that may be of concern include tinnitus or
loss of hearing, dizziness or loss of balance, changes in
urination frequency or urine production, increased
thirst, appetite loss, and nausea or vomiting.

Normal results
At the proper dosage and in the presence of gramnegative enteric (intestinal) bacteria, aminoglycosides
are very effective in treating an infection.

Abnormal results
In some cases, bacteria are resistant to antibiotics
that would normally kill them. This resistance
becomes apparent after repeated exposure to the antibiotic and arises from a mutation that alters the bacteria’s susceptibility to the drug. Various degrees of
resistance have been observed in bacteria that normally would be destroyed by aminoglycosides. In general, though, aminoglycoside effectiveness has held
up well over time.
Resources
BOOKS

Chambers, Henry F., W. Keith Hadley, and Ernest Jawetz.
‘‘Aminoglycosides & Spectinomycin.’’ In Basic and
GALE ENCYCLOPEDIA OF MEDICINE

Amnesia

Clinical Pharmacology, edited by Bertram G. Katzung,
7th ed. Stamford: Appleton & Lange, 1998.

Julia Barrett

Amitriptyline see Antidepressants, tricyclic
Amlodipine see Calcium channel blockers

I Amnesia
Definition
Amnesia refers to the loss of memory. Memory
loss may result from two-sided (bilateral) damage to
parts of the brain vital for memory storage, processing, or recall (the limbic system, including the hippocampus in the medial temporal lobe).

Hippocampus

Amygdala

Description
Amnesia can be a symptom of several neurodegenerative diseases; however, people whose primary
symptom is memory loss (amnesiacs), typically remain
lucid and retain their sense of self. They may even be
aware that they suffer from a memory disorder.
People who experience amnesia have been instrumental in helping brain researchers determine how
the brain processes memory. Until the early 1970s,
researchers viewed memory as a single entity.
Memory of new experiences, motor skills, past events,
and previous conditioning were grouped together in
one system that relied on a specific area of the brain.
If all memory were stored in the same way, it would
be reasonable to deduce that damage to the specific
brain area would cause complete memory loss. However, studies of amnesiacs counter that theory. Such
research demonstrates that the brain has multiple systems for processing, storing, and drawing on memory.

Causes and symptoms
Amnesia has several root causes. Most are traceable to brain injury related to physical trauma, disease,
infection, drug and alcohol abuse, or reduced blood
flow to the brain (vascular insufficiency). In WernickeKorsakoff syndrome, for example, damage to the
memory centers of the brain results from the use of
alcohol or malnutrition. Infections that damage brain
tissue, including encephalitis and herpes, can also
cause amnesia. If the amnesia is thought to be of
psychological origin, it is termed psychogenic.
GALE ENCYCLOPEDIA OF MEDICINE

Memory loss may result from bilateral damage to the limbic
system of the brain responsible for memory storage, processing, and recall. (Illustration by Electronic Illustrators Group).

There are at least three general types of amnesia:


Anterograde. This form of amnesia follows brain
trauma and is characterized by the inability to
remember new information. Recent experiences and
short-term memory disappear, but victims can recall
events prior to the trauma with clarity.



Retrograde. In some ways, this form of amnesia is
the opposite of anterograde amnesia: the victim can
recall events that occurred after a trauma, but cannot
remember previously familiar information or the
events preceding the trauma.



Transient global amnesia. This type of amnesia has
no consistently identifiable cause, but researchers
have suggested that migraines or transient ischemic
attacks may be the trigger. (A transient ischemic
attack, sometimes called ‘‘a small stroke,’’ occurs
when a blockage in an artery temporarily blocks
off blood supply to part of the brain.) A victim
experiences sudden confusion and forgetfulness.
Attacks can be as brief as 30-60 minutes or can
last up to 24 hours. In severe attacks, a person is
completely disoriented and may experience retrograde amnesia that extends back several years.
While very frightening for the patient, transient
global amnesia generally has an excellent prognosis
for recovery.
159

Amniocentesis

KEY TERMS
Classical conditioning—The memory system that
links perceptual information to the proper motor
response. For example, Ivan Pavlov conditioned a
dog to salivate when a bell was rung.
Emotional conditioning—The memory system that
links perceptual information to an emotional
response. For example, spotting a friend in a
crowd causes a person to feel happy.
Explicit memory—Conscious recall of facts and
events that is classified into episodic memory
(involves time and place) and semantic memory
(does not involve time and place). For example,
an amnesiac may remember he has a wife (semantic memory), but cannot recall his last conversation
with her (episodic memory).
Limbic system—The brain structures involved in
memory.
Magnetic resonance imaging (MRI)—MRI uses a
large circular magnet and radio waves to generate
signals from atoms in the body. These signals are
used to construct images of internal structures.
Motor skill learning—This memory system is associated with physical movement and activity. For
example, learning to swim is initially difficult, but
once an efficient stroke is learned, it requires little
conscious effort.
Neurodegenerative disease—A disease in which
the nervous system progressively and irreversibly
deteriorates.
Priming memory—The memory system that joins
perceptual and conceptual representations.
Transient ischemic attack—A sudden and brief
blockage of blood flow in the brain.
Working memory—The memory system that
relates to the task at hand and coordinates recall
of memories necessary to complete it.

the brain has been damaged, and blood work to exclude
treatable metabolic causes or chemical imbalances.

Treatment
Treatment depends on the root cause of amnesia
and is handled on an individual basis. Regardless of
cause, cognitive rehabilitation may be helpful in learning
strategies to cope with memory impairment.

Prognosis
Some types of amnesia, such as transient global
amnesia, are completely resolved and there is no permanent loss of memory. Others, such as Korsakoff
syndrome, associated with prolonged alcohol abuse
or amnesias caused by severe brain injury, may be
permanent. Depending on the degree of amnesia and
its cause, victims may be able to lead relatively normal
lives. Amnesiacs can learn through therapy to rely on
other memory systems to compensate for what is lost.

Prevention
Amnesia is only preventable in so far as brain
injury can be prevented or minimized. Common
sense approaches include wearing a helmet when bicycling or participating in potentially dangerous sports,
using automobile seat belts, and avoiding excessive
alcohol or drug use. Brain infections should be treated
swiftly and aggressively to minimize the damage due
to swelling. Victims of strokes, brain aneurysms, and
transient ischemic attacks should seek immediate
medical treatment.
Resources
PERIODICALS

Squire, Larry R., and Stuart M. Zola. ‘‘Amnesia,
Memory and Brain Systems.’’ Philosophical
Transactions of the Royal Society of London, Series B
352 (1997): 1663.

Julia Barrett

Diagnosis
In diagnosing amnesia and its cause, doctors look
at several factors. During a physical examination, the
doctor inquires about recent traumas or illnesses, drug
and medication history, and checks the patient’s general
health. Psychological exams may be ordered to determine the extent of amnesia and the memory system
affected. The doctor may also order imaging tests such
as magnetic resonance imaging (MRI) to reveal whether
160

I Amniocentesis
Definition
Amniocentesis is a procedure used to diagnose fetal
defects in the early second trimester of pregnancy. A
sample of the amniotic fluid, which surrounds a fetus
GALE ENCYCLOPEDIA OF MEDICINE

Amniocentesis
A physician uses an ultrasound monitor (left) to position the needle for insertion into the amnion when performing amniocentesis. (Photograph by Will and Deni McIntyre, Photo Researchers, Inc. Reproduced by permission.)

in the womb, is collected through a pregnant woman’s
abdomen using a needle and syringe. Tests performed
on fetal cells found in the sample can reveal the presence
of many types of genetic disorders, thus allowing
doctors and prospective parents to make important
decisions about early treatment and intervention.

Purpose
Since the mid-1970s, amniocentesis has been used
routinely to test for Down syndrome, by far the most
common, nonhereditary, genetic birth defect, afflicting about one in every 1,000 babies. By 1997, approximately 800 different diagnostic tests were available,
most of them for hereditary genetic disorders such
as Tay-Sachs disease, sickle cell anemia, hemophilia,
muscular dystrophy and cystic fibrosis.
Amniocentesis, often called amnio, is recommended for women who will be older than 35 on
their due-date. It is also recommended for women
who have already borne children with birth defects,
or when either of the parents has a family history of a
birth defect for which a diagnostic test is available.
GALE ENCYCLOPEDIA OF MEDICINE

Another reason for the procedure is to confirm indications of Down syndrome and certain other defects
which may have shown up previously during routine
maternal blood screening.
The risk of bearing a child with a nonhereditary
genetic defect such as Down syndrome is directly
related to a woman’s age–the older the woman, the
greater the risk. Thirty-five is the recommended age to
begin amnio testing because that is the age at which the
risk of carrying a fetus with such a defect roughly
equals the risk of miscarriage caused by the procedure–about one in 200. At age 25, the risk of giving
birth to a child with this type of defect is about one in
1,400; by age 45 it increases to about one in 20. Nearly
half of all pregnant women over 35 in the United States
undergo amniocentesis and many younger women also
decide to have the procedure. Notably, some 75% of all
Down syndrome infants born in the United States each
year are to women younger than 35.
One of the most common reasons for performing
amniocentesis is an abnormal alpha-fetoprotein
(AFP) test. Alpha-fetoprotein is a protein produced
161

Amniocentesis

KEY TERMS
Alpha-fetoprotein (AFP)—A protein normally produced by the liver of a fetus and detectable in maternal blood samples. AFP screening measures the
amount of alpha-fetoprotein in the blood. Levels
outside the norm may indicate fetal defects.
Anencephaly—A hereditary defect resulting in the
partial to complete absence of a brain and spinal
cord. It is fatal.
Chorionic villus sampling (CVS)—A procedure
similar to amniocentesis, except that cells are
taken from the chorionic membrane for testing.
These cells, called chorionic villus cells, eventually
become the placenta. The samples are collected
either through the abdomen, as in amnio, or
through the vagina. CVS can be done earlier in the
pregnancy than amnio, but carries a somewhat
higher risk.
Chromosome—Chromosomes are the strands of
genetic material in a cell that occur in nearly
identical pairs. Normal human cells contain 23
chromosome pairs–one in each pair inherited
from the mother, and one from the father. Every
human cell contains the exact same set of
chromosomes.
Down syndrome—The most prevalent of a class of
genetic defects known as trisomies, in which cells
contain three copies of certain chromosomes rather

by the fetus and present in the mother’s blood. A
simple blood screening, usually conducted around
the 15th week of pregnancy, can determine the AFP
levels in the mother’s blood. Levels that are too high or
too low may signal possible fetal defects. Because this
test has a high false-positive rate, another test such as
amnio is recommended whenever the AFP levels fall
outside the normal range.
Amniocentesis is generally performed during the
16th week of pregnancy, with results usually available
within three weeks. It is possible to perform an amnio
as early as the 11th week but this is not usually
recommended because there appears to be an
increased risk of miscarriage when done at this time.
The advantage of early amnio and speedy results lies
in the extra time for decision making if a problem is
detected. Potential treatment of the fetus can begin
earlier. Important, also, is the fact that elective abortions are safer and less controversial the earlier they
are performed.
162

than the usual two. Down syndrome, or trisomy 21,
usually results from three copies of chromosome 21.
Genetic—The term refers to genes, the basic units of
biological heredity, which are contained on the
chromosomes, and contain chemical instructions
which direct the development and functioning of
an individual.
Hereditary—Something which is inherited–passed
down from parents to offspring. In biology and medicine, the word pertains to inherited genetic
characteristics.
Maternal blood screening—Maternal blood screening is normally done early in pregnancy to test for a
variety of conditions. Abnormal amounts of certain
proteins in a pregnant woman’s blood raise the probability of fetal defects. Amniocentesis is recommended if such a probability occurs.
Tay-Sachs disease—An inherited disease prevalent
among the Ashkenazi Jewish population of the
United States. Infants with the disease are unable to
process a certain type of fat which accumulates in
nerve and brain cells, causing mental and physical
retardation, and death by age four.
Ultrasound—A technique which uses highfrequency sound waves to create a visual image (a
sonogram) of soft tissues. The technique is routinely
used in prenatal care and diagnosis.

Precautions
As an invasive surgical procedure, amnio poses a
real, although small, risk to the health of a fetus.
Parents must weigh the potential value of the knowledge gained, or indeed the reassurance that all is well,
against the small risk of damaging what is in all probability a normal fetus. The serious emotional and
ethical dilemmas that adverse test results can bring
must also be considered. The decision to undergo
amnio is always a matter of personal choice.

Description
The word amniocentesis literally means ‘‘puncture
of the amnion,’’ the thin-walled sac of fluid in which a
developing fetus is suspended during pregnancy.
During the sampling procedure, the obstetrician inserts
a very fine needle through the woman’s abdomen into
the uterus and amniotic sac and withdraws approximately one ounce of amniotic fluid for testing. The
GALE ENCYCLOPEDIA OF MEDICINE

The physician uses ultrasound images to guide
needle placement and collect the sample, thereby
minimizing the risk of fetal injury and the need for
repeated needle insertions. Once the sample is collected, the woman can return home after a brief
observation period. She may be instructed to rest
for the first 24 hours and to avoid heavy lifting for
two days.
The sample of amniotic fluid is sent to a laboratory where fetal cells contained in the fluid are isolated
and grown in order to provide enough genetic material
for testing. This takes about seven to 14 days. The
material is then extracted and treated so that visual
examination for defects can be made. For some disorders, like Tay-Sachs, the simple presence of a telltale
chemical compound in the amniotic fluid is enough to
confirm a diagnosis. Depending on the specific tests
ordered, and the skill of the lab conducting them, all
the results are available between one and four weeks
after the sample is taken.
Cost of the procedure depends on the doctor, the
lab, and the tests ordered. Most insurers provide coverage for women over 35, as a follow-up to positive
maternal blood screening results, and when genetic
disorders run in the family.
An alternative to amnio, now in general use, is
chorionic villus sampling, or CVS, which can be performed as early as the eighth week of pregnancy.
While this allows for the possibility of a first trimester
abortion, if warranted, CVS is apparently also riskier
and is more expensive. The most promising area of
new research in prenatal testing involves expanding
the scope and accuracy of maternal blood screening
as this poses no risk to the fetus.

Preparation
It is important for a woman to fully understand
the procedure and to feel confident in the obstetrician
performing it. Evidence suggests that a physician’s
experience with the procedure reduces the chance of
mishap. Almost all obstetricians are experienced in
performing amniocentesis. The patient should feel
free to ask questions and seek emotional support
before, during and after the amnio is performed.

Physical aftercare
During and immediately following the sampling
procedure, a woman may experience dizziness, nausea,
a rapid heartbeat, and cramping. Once past these
immediate hurdles, the physician will send the
woman home with instructions to rest and to report
any complications requiring immediate treatment,
including:


vaginal bleeding. The appearance of blood could
signal a problem.



premature labor. Unusual abdominal pain and/or
cramping may indicate the onset of premature labor.
Mild cramping for the first day or two following the
procedure is normal.



signs of infection. Leaking of amniotic fluid or unusual vaginal discharge, and fever could signal the
onset of infection.
Emotional aftercare

Once the procedure has been safely completed, the
anxiety of waiting for the test results can prove to be
the worst part of the process. A woman should seek
and receive emotional support from family and
friends, as well as from her obstetrician and family
doctor. Professional counseling may also prove necessary, particularly if a fetal defect is discovered.

Risks
Most of the risks and short-term side effects associated with amniocentesis relate to the sampling procedure and have been discussed above. A successful
amnio sampling results in no long-term side effects.
Risks include:


maternal/fetal hemorrhaging. While spotting in
pregnancy is fairly common, bleeding following
amnio should always be investigated.



infection. Infection, although rare, can occur after
amniocentesis. An unchecked infection can lead to
severe complications.



fetal injury. A very slight risk of injury to the fetus
resulting from contact with the amnio needle does exist.



miscarriage. The rate of miscarriage occurring
during standard, second trimester amnio appears to
be approximately 0.5%. This compares to a miscarriage rate of 1% for CVS. Many fetuses with severe
genetic defects miscarry naturally during the first
trimester.



the trauma of difficult family-planning decisions.
The threat posed to parental and family mental

Aftercare
Necessary aftercare falls into two categories,
physical and emotional.
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163

Amniocentesis

relatively painless procedure is performed on an outpatient basis, sometimes using local anesthesia.

Amputation

health from the trauma accompanying an abnormal
test result can not be underestimated.

I Amputation
Definition

Normal results
Negative results from an amnio analysis indicate
that everything about the fetus appears normal and
the pregnancy can continue without undue concern. A
negative result for Down syndrome means that it is
99% certain that the disease does not exist.
An overall ‘‘normal’’ result does not, however,
guarantee that the pregnancy will come to term, or
that the fetus does not suffer from some other defect.
Laboratory tests are not 100% accurate at detecting
targeted conditions, nor can every possible fetal condition be tested for.

Amputation is the intentional surgical removal of
a limb or body part. It is performed to remove diseased
tissue or relieve pain.

Purpose
Arms, legs, hands, feet, fingers, and toes can be
amputated. Most amputations involve small body
parts such as a finger, rather than an entire limb.
About 65,000 amputations are performed in the
United States each year.
Amputation is performed for the following reasons:


to remove tissue that no longer has an adequate
blood supply



to remove malignant tumors



because of severe trauma to the body part

Abnormal results
Positive results on an amnio analysis indicate the
presence of the fetal defect being tested for, with an
accuracy approaching 100%. Prospective parents are
then faced with emotionally and ethically difficult
choices regarding treatment options, the prospect of
dealing with a severely affected newborn, and the
option of elective abortion. At this point, the parents
need expert medical advice and counseling.
Resources
PERIODICALS

Dreisbach, Shaun. ‘‘Amnio Alternative.’’ Working Mother
(March 1997): 11.
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th St., S.W., P.O. Box 96920, Washington, DC
20090-6920. <http://www.acog.org>.

The blood supply to an extremity can be cut off
because of injury to the blood vessel, hardening of
the arteries, arterial embolism, impaired circulation
as a complication of diabetes mellitus, repeated severe
infection that leads to gangrene, severe frostbite,
Raynaud’s disease, or Buerger’s disease.
More than 90% of amputations performed in the
United States are due to circulatory complications of
diabetes. Sixty to eighty percent of these operations
involve the legs or feet. Although attempts have been
made in the United States to better manage diabetes
and the foot ulcers that can be complications of the
disease, the number of resulting amputations has not
decreased.

Precautions

OTHER

Holbrook Jr., Harold R. Stanford University School of
MedicineWeb Home Page. February 2001.
<http://www.stanford.edu/~holbrook>.

Amputations cannot be performed on patients
with uncontrolled diabetes mellitus, heart failure, or
infection. Patients with blood clotting disorders are
also not good candidates for amputation.

Kurt Richard Sternlof

Description

Amniotic fluid analysis see Amniocentesis
Amoxicillin see Penicillins
Amphetamines see Central nervous system
stimulants
Amphotericin B see Antifungal drugs,
systemic
164

Amputations can be either planned or emergency
procedures. Injury and arterial embolisms are the
main reasons for emergency amputations. The operation is performed under regional or general anesthesia
by a general or orthopedic surgeon in a hospital operating room.
Details of the operation vary slightly depending
on what part is to be removed. The goal of all
GALE ENCYCLOPEDIA OF MEDICINE

Amputation

Exposed
muscle

Skin flap
Femur
Sciatic
nerve

Figure A

Figure B

Figure C

Figure D

Amputation of leg. Figure A: After the surgeon creates two flaps of skin and tissue, the muscle is cut and the main artery and
veins of the femur bone are exposed. Figure B: The surgeon severs the main artery and veins. New connections are formed
between them, restoring blood circulation. The sciatic nerve is then pulled down, clamped and tied, and severed. Figure C: The
surgeon saws through the exposed femur bone. Figure D: The muscles are closed and sutured over the bone. The remaining
skin flaps are then sutured together, creating a stump. (Illustration by Electronic Illustrators Group.)

amputations is twofold: to remove diseased tissue so
that the wound will heal cleanly, and to construct a
stump that will allow the attachment of a prosthesis or
artificial replacement part.

amputation. The goal of the surgeon is to find the
place where healing is most likely to be complete,
while allowing the maximum amount of limb to
remain for effective rehabilitation.

The surgeon makes an incision around the part to
be amputated. The part is removed, and the bone is
smoothed. A flap is constructed of muscle, connective
tissue, and skin to cover the raw end of the bone. The
flap is closed over the bone with sutures (surgical
stitches) that remain in place for about one month.
Often, a rigid dressing or cast is applied that stays in
place for about two weeks.

The greater the blood flow through an area, the
more likely healing is to occur. These tests are designed
to measure blood flow through the limb. Several or all
of them can be done to help choose the proper level of
amputation.

Preparation
Before an amputation is performed, extensive
testing is done to determine the proper level of
GALE ENCYCLOPEDIA OF MEDICINE



measurement of blood pressure in different parts of
the limb



xenon 133 studies, which use a radiopharmaceutical
to measure blood flow



oxygen tension measurements in which an oxygen electrode is used to measure oxygen pressure under the skin.
If the pressure is 0, the healing will not occur. If the
165

Amputation

KEY TERMS
Arterial embolism—A blood clot arising from
another location that blocks an artery.
Buerger’s disease—An episodic disease that
causes inflammation and blockage of the veins
and arteries of the limbs. It tends to be present
almost exclusively on men under age 40 who
smoke, and may require amputation of the hand
or foot.
Diabetes mellitus—A disease in which insufficient
insulin is made by the body to metabolize sugars.
Raynaud’s disease—A disease found mainly in
young women that causes decreased circulation
to the hands and feet. Its cause is unknown.

pressure reads higher than 40mm Hg (40 milliliters of
mercury), healing of the area is likely to be satisfactory.


laser Doppler measurements of the microcirculation
of the skin



skin fluorescent studies that also measure skin
microcirculation



skin perfusion measurements using a blood pressure
cuff and photoelectric detector



infrared measurements of skin temperature

No single test is highly predictive of healing, but
taken together, the results give the surgeon an excellent idea of the best place to amputate.

Aftercare
After amputation, medication is prescribed for
pain, and patients are treated with antibiotics to
discourage infection. The stump is moved often to
encourage good circulation. Physical therapy and
rehabilitation are started as soon as possible, usually
within 48 hours. Studies have shown that there is a
positive relationship between early rehabilitation
and effective functioning of the stump and prosthesis. Length of stay in the hospital depends on the
severity of the amputation and the general health
of the amputee, but ranges from several days to
two weeks.
Rehabilitation is a long, arduous process, especially for above the knee amputees. Twice daily physical
therapy is not uncommon. In addition, psychological
counseling is an important part of rehabilitation.
166

Many people feel a sense of loss and grief when they
lose a body part. Others are bothered by phantom
limb syndrome, where they feel as if the amputated
part is still in place. They may even feel pain in the limb
that does not exist. Many amputees benefit from joining self-help groups and meeting others who are also
living with amputation. Addressing the emotional
aspects of amputation often speeds the physical rehabilitation process.

Risks
Amputation is major surgery. All the risks associated with the administration of anesthesia exist,
along with the possibility of heavy blood loss and
the development of blood clots. Infection is of special concern to amputees. Infection rates in amputations average 15%. If the stump becomes infected, it
is necessary to remove the prosthesis and sometimes
to amputate a second time at a higher level.
Failure of the stump to heal is another major
complication. Nonhealing is usually due to an inadequate blood supply. The rate of nonhealing varies
from 5-30% depending on the facility. Centers that
specialize in amputation usually have the lowest rates
of complication.
Persistent pain in the stump or pain in the phantom limb is experienced by most amputees to some
degree. Treatment of phantom limb pain is difficult.
Finally, many amputees give up on the rehabilitation
process and discard their prosthesis. Better fitting
prosthetics and earlier rehabilitation have decreased
the incidence of this problem. Researchers and prosthetic manufacturers continue to refine the materials
and methods used to try to improve the comfort
and function of prosthetic devices for amputees.
For example, a 2004 study showed that a technique
called the bone bridge amputation technique helped
improve comfort and stability for transtibial
amputees.

Normal results
The five-year survival rate for all lower extremity
amputees is less than 50%. For diabetic amputees, the
rate is less than 40%. Up to 50% of people who have
one leg amputated because of diabetes will lose the
other within five years. Amputees who walk using a
prosthesis have a less stable gait. Three to five percent
of these people fall and break bones because of this
instability. Although the fractures can be treated,
about one-half of amputees who suffer them then
remain wheelchair bound.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

PERIODICALS

Edwards, Anthony R. ‘‘Study Helps Build Functional
Bridges for Amputee Patients.’’ Biomechanics (May 1,
2004): 17.
Jeffcoat, William. ‘‘Incidence of Amputation is a Poor
Measure of the Quality of Ulcer Care.’’ The Diabetic
Foot Summer (2004): 70–74.

Amylase—A digestive enzyme made primarily by
the pancreas and salivary glands.
Enzyme—A substance made and used by the body
to trigger specific chemical reactions.
Pancreatitis—Inflammation of the pancreas.

ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383.
<http://www.diabetes.org>.
OTHER

Amputation Prevention Global Resource Center Page.
February 2001. <http://www.diabetesresource.com>.

Tish Davidson, A.M.
Teresa G. Odle

strangulation or perforation can also cause unusually
high amylase levels.

Precautions
This is not a screening test for future pancreatic
disease.

Description

I Amylase tests
Definition
Amylase is a digestive enzyme made primarily by
the pancreas and salivary glands. Enzymes are substances made and used by the body to trigger specific
chemical reactions. The primary function of the
enzyme amylase is to break down starches in food so
that they can be used by the body. Amylase testing
is usually done to determine the cause of sudden
abdominal pain.

Purpose
Amylase testing is performed to diagnose a number of diseases that elevate amylase levels. Pancreatitis,
for example, is the most common reason for a high
amylase level. When the pancreas is inflamed, amylase
escapes from the pancreas into the blood. Within six to
48 hours after the pain begins, amylase levels in the
blood start to rise. Levels will stay high for several days
before gradually returning to normal.
There are other causes of increased amylase. An
ulcer that erodes tissue from the stomach and goes
into the pancreas will cause amylase to spill into the
blood. During a mumps infection, amylase from the
inflamed salivary glands increases. Amylase is also
found in the liver, fallopian tubes, and small intestine;
inflammation of these tissues also increases levels. Gall
bladder disease, tumors of the lung or ovaries, alcohol
poisoning, ruptured aortic aneurysm, and intestinal
GALE ENCYCLOPEDIA OF MEDICINE

Amylase testing is done on both blood and
urine. The laboratory may use any of several testing
methods that involve mixing the blood or urine sample with a substance with which amylase is known to
react. By measuring the end-product or the reaction
time, technicians can calculate the amount of amylase present in the sample. More sophisticated methods separately measure the amylase made by the
pancreas and the amylase made by the salivary
glands.
Urine testing is a better long-term monitor of
amylase levels. The kidneys quickly move extra
amylase from the blood into the urine. Urine levels
rise six to 10 hours after blood levels and stay high
longer. Urine is usually collected throughout a 2- or
24-hour time period. Results are usually available the
same day.

Preparation
In most cases, no special preparation is necessary
for a person undergoing an amylase blood test.
Patients taking longer term urine amylase tests will
be given a container and instructions for collecting
the urine at home. The urine should be refrigerated
until it is brought to the laboratory.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops reduces
167

Amylase tests

Resources

Amyloidosis

bruising. Applying warm packs to the puncture site
relieves discomfort.

Normal results
Normal results vary based on the laboratory and
the method used.

Abnormal results
Eight out of ten persons with acute pancreatitis
will have high amylase levels, up to four times the
normal level. Other causes of increased amylase, such
as mumps, kidney failure, pregnancy occurring in
the abdomen but outside the uterus (ectopic pregnancy), certain tumors, a penetrating ulcer, certain
complications of diabetes, and advanced pancreatic
cancer, are further investigated based on the person’s
symptoms, medical history, and the results of other
tests.
In kidney disease, the kidneys are not as efficient
at removing amylase from the blood. Amylase rises in
the blood, but stays at normal levels in the urine.
People with macroamylasia have large clumps of
amylase in their blood. These clumps are too large to
move through the kidney, so they stay in the blood.
Amylase levels in the blood will be high; levels in the
urine will be low.
Amylase levels may be low in severe liver disease
(including hepatitis), conditions in which the pancreas
fails to secrete enough enzyme for proper digestions
(pancreatic insufficiency), when toxic materials build
up in the blood during pregnancy (pre-eclampsia),
following burns, in thyroid disorders, and in advanced
cystic fibrosis. Some medications can raise or lower
levels.
Resources

Description
Amyloid proteins are manufactured by malfunctioning bone marrow. Amyloidosis, which occurs
when accumulated amyloid deposits impair normal
body function, can cause organ failure or death. It
is a rare disease, occurring in about eight of every
1,000,000 people. It affects males and females equally
and usually develops after the age of 40. At least 15
types of amyloidosis have been identified. Each one
is associated with deposits of a different kind of
protein.
Types of amyloidosis
The major forms of this disease are primary systemic, secondary, and familial or hereditary amyloidosis. There is also another form of amyloidosis
associated with Alzheimer’s disease.
Primary systemic amyloidosis usually develops
between the ages of 50 and 60. With about 2,000 new
cases diagnosed annually, primary systemic amyloidosis is the most common form of this disease in the
United States. Also known as light-chain-related amyloidosis, it may also occur in association with multiple
myeloma (bone marrow cancer).
Secondary amyloidosis is a result of chronic infection or inflammatory disease. It is often associated
with:


familial Mediterranean fever (a bacterial infection
characterized by chills, weakness, headache, and
recurring fever)



granulomatous ileitis (inflammation of the small
intestine)



Hodgkin’s disease (cancer of the lymphatic system)



leprosy



osteomyelitits (bacterial infection of bone and bone
marrow)



rheumatoid arthritis

BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnosticand
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Nancy J. Nordenson

I Amyloidosis
Definition
Amyloidosis is a progressive, incurable, metabolic
disease characterized by abnormal deposits of protein
in one or more organs or body systems.
168

Familial or hereditary amyloidosis is the only
inherited form of the disease. It occurs in members of
most ethnic groups, and each family has a distinctive
pattern of symptoms and organ involvement. Hereditary
amyloidosis is though to be autosomal dominant,
which means that only one copy of the defective gene
is necessary to cause the disease. A child of a parent
with familial amyloidosis has a 50-50 chance of developing the disease.
Amyloidosis can involve any organ or system in
the body. The heart, kidneys, gastrointestinal system,
and nervous system are affected most often. Other
GALE ENCYCLOPEDIA OF MEDICINE

Amyloid—A waxy, starch-like protein.
Peripheral nerves—Nerves that carry information
to and from the spinal cord.
Stem cells—Parent cells from which other cells are
made.

common sites of amyloid accumulation include the
brain, joints, liver, spleen, pancreas, respiratory system,
and skin.

Causes and symptoms
The cause of amyloidosis is unknown. Most
patients have gastrointestinal abnormalities, but
other symptoms vary according to the organ(s) or
system(s) affected by the disease. Usually the affected
organs are rubbery, firm, and enlarged.
Heart
Because amyloid protein deposits can limit the
heart’s ability to fill with blood between beats, even
the slightest exertion can cause shortness of breath. If
the heart’s electrical system is affected, the heart’s
rhythm may become erratic. The heart may also be
enlarged and heart murmurs may be present.
Congestive heart failure may result.

the legs. If nerves controlling bowel function are
involved, bouts of diarrhea alternate with periods of
constipation. If the disease affects nerves that regulate
blood pressure, patients may feel dizzy or faint when
they stand up suddenly.
Liver and spleen
The most common symptoms are enlargement of
these organs. Liver function is not usually affected
until quite late in the course of the disease. Protein
accumulation in the spleen can increase the risk of
rupture of this organ due to trauma.
Gastrointestinal system
The tongue may be inflammed, enlarged, and stiff.
Intestinal movement (motility) may be reduced.
Absorption of food and other nutrients may be
impaired (and may lead to malnutrition), and there
may also be bleeding, abdominal pain, constipation,
and diarrhea.
Skin
Skin symptoms occur in about half of all cases
of primary and secondary amyloidosis and in all
cases where there is inflammation or degeneration of
the peripheral nerves. Waxy-looking raised bumps
(papules) may appear on the face and neck, in the
groin, armpits, or anal area, and on the tongue or in
the ear canals. Swelling, hemorrhage beneath the skin
(purpura), hair loss, and dry mouth may also occur.
Respiratory system

Kidneys
The feet, ankles, and calves swell when amyloidosis
damages the kidneys. The kidneys become small and
hard, and kidney failure may result. It is not unusual for
a patient to lose 20-25 pounds and develop a distaste for
meat, eggs, and other protein-rich foods. Cholesterol
elevations that don’t respond to medication and protein
in the urine (proteinuria) are common.
Nervous system
Nervous system symptoms often appear in
patients with familial amyloidosis. Inflammation and
degeneration of the peripheral nerves (peripheral neuropathy) may be present. One of four patients with
amyloidosis has carpal tunnel syndrome, a painful
disorder that causes numbness or tingling in response
to pressure on nerves around the wrist. Amyloidosis
that affects nerves to the feet can cause burning or
numbness in the toes and soles and eventually weaken
GALE ENCYCLOPEDIA OF MEDICINE

Airways may be obstructed by amyloid deposits in
the nasal sinus, larynx and traches (windpipe).

Diagnosis
Blood and urine tests can reveal the presence of
amyloid protein, but tissue or bone-marrow biopsy
is necessary to positively diagnose amyloidosis. Once
the diagnosis has been confirmed, additional laboratory tests and imaging procedures are performed to
determine:


which type of amyloid protein is involved



which organ(s) or system(s) have been affected



how far the disease has progressed

Treatment
The goal of treatment is to slow down or stop
production of amyloid protein, eliminate existing
169

Amyloidosis

KEY TERMS

Amyotrophic lateral sclerosis

amyloid deposits, alleviate underlying disorders
(that give rise to secondary amyloidosis), and relieve
symptoms caused by heart or kidney damage.
Specialists in cardiology, hematology (the study of
blood and the tissues that form it), nephrology (the
study of kidney function and abnormalities), neurology (the study of the nervous system), and rheumatology (the study of disorders characterized by
inflammation or degeneration of connective tissue)
work together to assess a patient’s medical status and
evaluate the effects of amyloidosis on every part of
the body.
Colchicine (Colebenemid, Probeneaid), prednisone, (Prodium), and other anti-inflammatory drugs
can slow or stop disease progression. Bone-marrow
and stem-cell transplants can enable patients to tolerate higher and more effective doses of melphalan
(Alkeran) and other chemotherapy drugs prescribed
to combat this non-malignant disease. Surgery can
relieve nerve pressure and may be performed to correct
other symptom-producing conditions. Localized amyloid deposits can also be removed surgically. Dialysis
or kidney transplantation can lengthen and improve
the quality of life for patients whose amyloidosis
results in kidney failure. Heart transplants are rarely
performed.
Supportive measures
Although no link has been established between
diet and development of amyloid proteins, a patient
whose heart or kidneys have been affected by the
disease may be advised to use a diuretic or follow a
low-salt diet.

Prognosis
Most cases of amyloidosis are diagnosed after
the disease has reached an advanced stage. The course
of each patient’s illness is unique but death, usually
a result of heart disease or kidney failure, generally
occurs within a few years. Amyloidosis associated
by multiple myeloma usually has a poor prognosis.
Most patients with both diseases die within one to
two years.

Prevention
Genetic couseling may be helpful for patients with
hereditary amyloidosis and their families. Use of
Cholchicine in patients with familial Mediterranean
fever has successfully prevented amyloidosis.

170

Resources
ORGANIZATIONS

Amyloidosis Network International. 7118 Cole Creek Drive,
Houston, TX 77092-1421. (888) 1AMYLOID.
<http://www.health.gov/nhic/Scripts/
Entry.cfm?HRCode=HR2397>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Maureen Haggerty

I Amyotrophic lateral sclerosis
Definition
Amyotrophic lateral sclerosis (ALS) is a disease
that breaks down tissues in the nervous system
(a neurodegenerative disease) of unknown cause that
affects the nerves responsible for movement. It is also
known as motor neuron disease and Lou Gehrig’s
disease, after the baseball player whose career it ended.

Description
ALS is a disease of the motor neurons, those nerve
cells reaching from the brain to the spinal cord (upper
motor neurons) and the spinal cord to the peripheral
nerves (lower motor neurons) that control muscle
movement. In ALS, for unknown reasons, these
neurons die, leading to a progressive loss of the ability
to move virtually any of the muscles in the body. ALS
affects ‘‘voluntary’’ muscles, those controlled by conscious thought, such as the arm, leg, and trunk muscles. ALS, in and of itself, does not affect sensation,
thought processes, the heart muscle, or the ‘‘smooth’’
muscle of the digestive system, bladder, and other
internal organs. Most people with ALS retain function
of their eye muscles as well. However, various forms
of ALS may be associated with a loss of intellectual
function (dementia) or sensory symptoms.
ALS progresses rapidly in most cases. It is fatal
within three years for 50% of all people affected, and
within five years for 80%. Ten percent of people with
ALS live beyond eight years.

Causes and symptoms
Causes
The symptoms of ALS are caused by the death of
motor neurons in the spinal cord and brain. Normally,

GALE ENCYCLOPEDIA OF MEDICINE

Normal nerve fiber

Amyotrophic lateral sclerosis

NORMAL SPINAL NEURON

DISEASED SPINAL NEURON

Affected nerve fiber

Normal skeletal muscle

Wasted skeletal muscle

Amyotrophic lateral sclerosis (ALS) is caused by the degeneration and death of motor neurons in the spinal cord and brain.
These neurons convey electrical messages from the brain to the muscles to stimulate movement in the arms, legs, trunk, neck,
and head. As motor neurons degenerate, the muscles are weakened and cannot move as effectively, leading to muscle wasting.
(Illustration by Electronic Illustrators Group.)

these neurons convey electrical messages from the
brain to the muscles to stimulate movement in the
arms, legs, trunk, neck, and head. As motor neurons
die, the muscles they enervate cannot be moved as
effectively, and weakness results. In addition, lack of
stimulation leads to muscle wasting, or loss of bulk.
Involvement of the upper motor neurons causes
spasms and increased tone in the limbs, and abnormal
reflexes. Involvement of the lower motor neurons
causes muscle wasting and twitching (fasciculations).
Although many causes of motor neuron degeneration have been suggested for ALS, none has yet been
proven responsible. Results of recent research have
GALE ENCYCLOPEDIA OF MEDICINE

implicated toxic molecular fragments known as free
radicals. Some evidence suggests that a cascade of
events leads to excess free radical production inside
motor neurons, leading to their death. Why free radicals should be produced in excess amounts is unclear,
as is whether this excess is the cause or the effect of
other degenerative processes. Additional agents
within this toxic cascade may include excessive levels
of a neurotransmitter known as glutamate, which may
over-stimulate motor neurons, thereby increasing
free-radical production, and a faulty detoxification
enzyme known as SOD-1, for superoxide dismutase
type 1. The actual pathway of destruction is not
171

Amyotrophic lateral sclerosis

KEY TERMS
Aspiration—Inhalation of food or liquids into the
lungs.
Bulbar muscles—Muscles of the mouth and throat
responsible for speech and swallowing.
Fasciculations—Involuntary twitching of muscles.
Motor neuron—A nerve cell that controls a
muscle.
Riluzole (Rilutek)—The first drug approved in the
United States for the treatment of ALS.
Voluntary muscle—A muscle under conscious
control; contrasted with smooth muscle and heart
muscle which are not under voluntary control.

known, however, nor is the trigger for the rapid degeneration that marks ALS. Further research may show
that other pathways are involved, perhaps ones even
more important than this one. Autoimmune factors or
premature aging may play some role, as could viral
agents or environmental toxins.
Two major forms of ALS are known: familial and
sporadic. Familial ALS accounts for about 10% of all
ALS cases. As the name suggests, familial ALS is
believed to be caused by the inheritance of one or
more faulty genes. About 15% of families with this
type of ALS have mutations in the gene for SOD-1.
SOD-1 gene defects are dominant, meaning only one
gene copy is needed to develop the disease. Therefore,
a parent with the faulty gene has a 50% chance of
passing the gene along to a child.
Sporadic ALS has no known cause. While many
environmental toxins have been suggested as causes,
to date no research has confirmed any of the candidates investigated, including aluminum and mercury
and lead from dental fillings. As research progresses, it
is likely that many cases of sporadic ALS will be
shown to have a genetic basis as well.
A third type, called Western Pacific ALS, occurs
in Guam and other Pacific islands. This form combines symptoms of both ALS and Parkinson’s disease.
Symptoms
The earliest sign of ALS is most often weakness in
the arms or legs, usually more pronounced on one side
than the other at first. Loss of function is usually more
rapid in the legs among people with familial ALS and
in the arms among those with sporadic ALS. Leg
172

weakness may first become apparent by an increased
frequency of stumbling on uneven pavement, or an
unexplained difficulty climbing stairs. Arm weakness
may lead to difficulty grasping and holding a cup, for
instance, or loss of dexterity in the fingers.
Less often, the earliest sign of ALS is weakness in
the bulbar muscles, those muscles in the mouth and
throat that control chewing, swallowing, and speaking. A person with bulbar weakness may become
hoarse or tired after speaking at length, or speech
may become slurred.
In addition to weakness, the other cardinal signs
of ALS are muscle wasting and persistent twitching
(fasciculation). These are usually seen after weakness
becomes obvious. Fasciculation is quite common in
people without the disease, and is virtually never the
first sign of ALS.
While initial weakness may be limited to one
region, ALS almost always progresses rapidly to
involve virtually all the voluntary muscle groups in
the body. Later symptoms include loss of the ability
to walk, to use the arms and hands, to speak clearly or
at all, to swallow, and to hold the head up. Weakness
of the respiratory muscles makes breathing and
coughing difficult, and poor swallowing control
increases the likelihood of inhaling food or saliva
(aspiration). Aspiration increases the likelihood of
lung infection, which is often the cause of death.
With a ventilator and scrupulous bronchial hygiene,
a person with ALS may live much longer than the
average, although weakness and wasting will continue to erode any remaining functional abilities.
Most people with ALS continue to retain function
of the extraocular muscles that move their eyes,
allowing some communication to take place with
simple blinks or through use of a computer-assisted
device.

Diagnosis
The diagnosis of ALS begins with a complete
medical history and physical exam, plus a neurological
examination to determine the distribution and extent
of weakness. An electrical test of muscle function,
called an electromyogram, or EMG, is an important
part of the diagnostic process. Various other tests,
including blood and urine tests, x rays, and CT
scans, may be done to rule out other possible causes
of the symptoms, such as tumors of the skull base or
high cervical spinal cord, thyroid disease, spinal
arthritis, lead poisoning, or severe vitamin deficiency.
ALS is rarely misdiagnosed following a careful review
of all these factors.
GALE ENCYCLOPEDIA OF MEDICINE

There is no cure for ALS, and no treatment that
can significantly alter its course. There are many
things which can be done, however, to help maintain
quality of life and to retain functional ability even in
the face of progressive weakness.
As of the early 2000s, only one drug had been
approved for treatment of ALS. Riluzole (Rilutek)
appears to provide on average a three-month increase
in life expectancy when taken regularly early in the
disease, and shows a significant slowing of the loss of
muscle strength. Riluzole acts by decreasing glutamate release from nerve terminals. Experimental
trials of nerve growth factor have not demonstrated
any benefit. No other drug or vitamin currently available has been shown to have any effect on the course
of ALS.
A physical therapist works with an affected
person and family to implement exercise and stretching programs to maintain strength and range of
motion, and to promote general health. Swimming
may be a good choice for people with ALS, as it
provides a low-impact workout to most muscle
groups. One result of chronic inactivity is contracture, or muscle shortening. Contractures limit a person’s range of motion, and are often painful. Regular
stretching can prevent contracture. Several drugs are
available to reduce cramping, a common complaint
in ALS.
An occupational therapist can help design solutions to movement and coordination problems, and
provide advice on adaptive devices and home
modifications.
Speech and swallowing difficulties can be minimized or delayed through training provided by a
speech-language pathologist. This specialist can also
provide advice on communication aids, including
computer-assisted devices and simpler word boards.
Nutritional advice can be provided by a nutritionist. A person with ALS often needs softer foods to
prevent jaw exhaustion or choking. Later in the
disease, nutrition may be provided by a gastrostomy
tube inserted into the stomach.
Mechanical ventilation may be used when breathing becomes too difficult. Modern mechanical ventilators are small and portable, allowing a person with
ALS to maintain the maximum level of function and
mobility. Ventilation may be administered through a
mouth or nose piece, or through a tracheostomy tube.
This tube is inserted through a small hole made in the
windpipe. In addition to providing direct access to the
GALE ENCYCLOPEDIA OF MEDICINE

airway, the tube also decreases the risk aspiration.
While many people with rapidly progressing ALS
choose not to use ventilators for lengthy periods,
they are increasingly being used to prolong life for a
short time.
The progressive nature of ALS means that most
persons will eventually require full-time nursing care.
This care is often provided by a spouse or other family
member. While the skills involved are not difficult
to learn, the physical and emotional burden of care
can be overwhelming. Caregivers need to recognize
and provide for their own needs as well as those of
people with ALS, to prevent depression, burnout, and
bitterness.
Throughout the disease, a support group can provide important psychological aid to affected persons
and their caregivers as they come to terms with the
losses ALS inflicts. Support groups are sponsored by
both the ALS Society and the Muscular Dystrophy
Association.

Alternative treatment
Given the grave prognosis and absence of traditional medical treatments, it is not surprising that a
large number of alternative treatments have been
tried for ALS. Two studies published in 1988 suggested that amino-acid therapies may provide some
improvement for some people with ALS. While individual reports claim benefits for megavitamin therapy, herbal medicine, and removal of dental fillings,
for instance, no evidence suggests that these offer
any more than a brief psychological boost, often
followed by a more severe letdown when it becomes
apparent the disease has continued unabated.
However, once the causes of ALS are better understood, alternative therapies may be more intensively
studied. For example, if damage by free radicals
turns out to be the root of most of the symptoms,
antioxidant vitamins and supplements may be used
more routinely to slow the progression of ALS. Or, if
environmental toxins are implicated, alternative
therapies with the goal of detoxifying the body may
be of some use.

Prognosis
ALS usually progresses rapidly, and leads to
death from respiratory infection within three to five
years in most cases. The slowest disease progression is
seen in those who are young and have their first symptoms in the limbs. About 10% of people with ALS live
longer than eight years.
173

Amyotrophic lateral sclerosis

Treatment

Anabolic steroid use

Prevention

I Anabolic steroid use

There is no known way to prevent ALS or to alter
its course.

Anabolic steroids are drugs containing hormones,
or hormone-like substances, that are used to increase
strength and promote muscle growth.

Resources
BOOKS

Feldman, Eva L. ‘‘Motor neuron diseases.’’ In Cecil
Textbook of Medicine, edited by Lee Goldman
and J. Claude Bennett, 21st ed. Philadelphia:
W.B. Saunders, 2000, pp. 2089-2092.
PERIODICALS

Ansevin CF. ‘‘Treatment of ALS with pleconaril.’’
Neurology 56, no. 5 (2001): 691-692.
Eisen, A., and M. Weber. ‘‘The motor cortex and amyotrophiclateral sclerosis.’’ Muscle and Nerve 24, no. 4
(2001): 564-573.
Gelanis DF. ‘‘Respiratory Failure or Impairment in
Amyotrophic Lateral Sclerosis.’’ Current treatment
options in neurology 3, no. 2 (2001): 133-138.
Ludolph AC. ‘‘Treatment of amyotrophic lateral sclerosis–
what is the next step?’’ Journal of Neurology 246,
Supplement 6 (2000): 13-18.
Pasetti, C., and G. Zanini. ‘‘The physician-patient relationship
inamyotrophic lateral sclerosis.’’ Neurological Science 21,
no. 5 (2000): 318-323.
Robberecht W. ‘‘Genetics of amyotrophic lateral sclerosis.’’
Journal of Neurology 246, Supplement 6 (2000): 2-6.
Robbins, R.A., Z. Simmons, B.A. Bremer, S.M. Walsh, and
S. Fischer. ‘‘Quality of life in ALS is maintained as
physical function declines.’’ Neurology 56, no. 4 (2001):
442-444.
ORGANIZATIONS

American Medical Association. 515 N. State Street,
Chicago, IL 60610. (312) 464-5000. <http://www.
ama-assn.org/>.
Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson AZ 85718-3208. (520) 529-2000 or (800)
572-1717. <http://www.mdausa.org>.
OTHER

ALS Society of Canada. <http://www.als.ca/>.
ALS Survival Guide. <http://www.lougehrigsdisease.net/>.
American Academy of Family Physicians. <http://
www.aafp.org/afp/990315ap/1489.html>.
National Institute of Neurological Disorders and Stroke.
<http://www.ninds.nih.gov/health_and_medical/
disorders/amyotrophiclateralsclerosis_doc.htm>.
National Library of Medicine. <http://www.nlm.nih.gov/
medlineplus/amyotrophiclateralsclerosis.html>.
National Organization for Rare Diseases. <http://
www.stepstn.com/cgi-win/nord.exe?proc=
Redirect&type=rdb_sum&id=57.htm>.
World Federation of Neurology. <http://www.wfnals.org/>.

L. Fleming Fallon, Jr., MD, DrPH
174

Definition

Description
Steroids are a synthetic version of the human
hormone called testosterone. Testosterone stimulates
and maintains the male sexual organs. It also stimulates development of bones and muscle, promotes
skin and hair growth, and can influence emotions
and energy levels. In males, testosterone is produced
by the testicles and the adrenal gland. Women have
only the amount of testosterone produced by the
adrenal gland—much less than men have. This is
why testosterone is often called a ‘‘male’’ hormone.
There are more than 100 different types of anabolic
steroids that have been developed, and each requires
a prescription to be used legally in the United States.
The average adult male naturally produces 2.5 to 11
milligrams of testosterone daily. The average steroid
abuser often takes more than 100 mg a day, through
‘‘stacking’’ or combining several different brands of
steroids.
Medical uses
Anabolic steroids were first developed in the
1930s in Europe, in part to increase the physical
strength of German soldiers. Anabolic steroids were
tried by physicians for many other purposes in the
1940s and 1950s with varying success. Disadvantages
outweighed benefits for most purposes, and during the
later decades of the twentieth century medical use in
North America and Europe was restricted to a few
conditions. These include:


Bone marrow stimulation: During the second half of
the twentieth century anabolic steroids were the
mainstay of therapy for hypoplastic anemia not due
to nutrient deficiency, especially aplastic anemia.
Anabolic steroids were slowly replaced by synthetic
protein hormones that selectively stimulate growth
of blood cell precursors.



Growth stimulation: Anabolic steroids were used
heavily by pediatric endocrinologists for children
with growth failure from the 1960s through the
1980s. Availability of synthetic growth hormone
and increasing social stigmatization of anabolic steroids led to reduction of this use.
GALE ENCYCLOPEDIA OF MEDICINE



Stimulation of appetite and preservation of muscle
mass: Anabolic steroids have been given to people
with chronic wasting conditions such as cancer and
HIV/AIDS.
Induction of male puberty: Androgens are given to
many boys distressed about extreme delay of puberty. Testosterone is as of 2005 nearly the only androgen used for this purpose, but synthetic anabolic
steroids were often used prior to the 1980s.



To treat certain kinds of breast cancer in some women.



To treat angioedema, which causes swelling of the face,
arms, legs, throat, windpipe, bowels, or sexual organs.
Abuse of steroids

The controversy surrounding steroid abuse began
in the 1950s during the Olympic Games when the
athletic community discovered that athletes from
Russia and some East European nations, which had
dominated the games, had taken large doses of steroids. Many of the male athletes developed such large
prostate glands (a gland located near the bladder and
urethra that aids in semen production) that they
needed a tube inserted in order to urinate. Some of
the female athletes developed so many male characteristics chromosome tests were necessary to prove that
they were still women. Competitive weightlifters also
began using steroids in the 1950s as a way to increase
their athletic performance. Use gradually spread
throughout the world among athletes in other sports.
Concerns over the growing illicit market and the
prevalence of abuse, combined with the possibility of
harmful long-term effects of steroids use, led the U.S.
Congress in 1991 to place anabolic steroids in
Schedule III of the Controlled Substances Act
(CSA). The CSA defines anabolic steroids as any
drug or hormonal substance chemically and pharmacologically related to testosterone (other than estrogens, progestins, and corticosteroids) that promotes
muscle growth. Most illicit anabolic steroids are sold
at gyms, bodybuilding competitions, and through the
mail and Internet. For the most part, these substances
are smuggled into the United States. Anabolic steroids
commonly encountered on the illicit market include:
boldenone (Equipoise), ethlestrenol (Maxibolin),
fluoxymesterone (Halotestin), methandriol, methandrostenolone (Dianabol), methyltestosterone, nandrolone (Durabolin, DecaDurabolin), oxandrolone
(Anavar), oxymetholone (Anadrol), stanozolol
(Winstrol), testosterone (including sustanon), and
trenbolone (Finajet). In addition, a number of counterfeit products are sold as anabolic steroids.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Adrenal gland—An endocrine gland located
above each kidney. The inner part of each gland
secretes epinephrine and the outer part secretes
steroids.
Androgen—A natural or artificial steroid that acts
as a male sex hormone. Androgens are responsible
for the development of male sex organs and secondary sexual characteristics. Testosterone and
androsterone are androgens.
Androstenedione—Also called ‘‘andro,’’ this hormone occurs naturally during the making of testosterone and estrogen.
Catabolic—A metabolic process in which energy is
released through the conversion of complex molecules into simpler ones.
Corticosteroids—A steroid hormone produced by
the adrenal gland and involved in metabolism and
immune response.
Endocrinologist—A medical specialist who treats
endocrine (glands that secrete hormones internally directly into the lymph or bloodstream)
disorders.
Estrogen—Any of several steroid hormones, produced mainly in the ovaries, that stimulate estrus
and the development of female secondary sexual
characteristics.
Hormone—A chemical substance produced in the
body’s endocrine glands or certain other cells that
exerts a regulatory or stimulatory effect, for example, in metabolism.
Hypoplastic anemia—Anemia that is characterized
by defective function of the blood-forming organs
(such as bone marrow) and is caused by toxic
agents such as chemicals or x rays. Anemia is a
blood condition in which there are too few red
blood cells or the red blood cells are deficient in
hemoglobin.
Progestins—A female steroid sex hormone.
Prohormones—A physiologically inactive precursor of a hormone.
Prostate gland—An O-shaped gland in males that
secretes a fluid into the semen that acts to improve
the movement and viability of sperm.
Testosterone—A male steroid hormone produced
in the testicles and responsible for the development
of secondary sex characteristics.

175

Anabolic steroid use



Anabolic steroid use

In 2004, federal health officials initiated a crackdown on companies that manufacture, market, or
distribute products containing androstenedione, or
‘‘andro,’’ due to concerns about the safety of the substance. Widely marketed to athletes and body
builders, androstenedione has been advertised to promote muscle growth, improve muscular strength,
reduce fat, and slow aging. Androstenedione acts like
a steroid once it is metabolized by the body and can
pose similar kinds of health risks. People produce
androstenedione naturally during the making of testosterone and estrogen. When people consume
androstenedione, it is converted into testosterone
and estrogen. Scientific evidence shows that when
androstenedione is taken over time and in sufficient
quantities, it may increase the risk of serious and lifethreatening diseases, including liver failure.

breasts, and enlarged prostate glands. Women frequently show signs of masculinity and may be at higher
risk for certain types of cancer and the possibility of
birth defects in their children. Steroids fool the body
into thinking that testosterone is being produced. The
body, sensing an excess of testosterone, shuts down
bodily functions involving testosterone, such as bone
growth. The ends of long bones fuse together and stop
growing, resulting in stunted growth.

On January 20, 2005, the Anabolic Steroid Control
Act of 2004 took effect, amending the Controlled
Substance Act by placing both anabolic steroids and
prohormones on a list of controlled substances, making
possession of the banned substances a federal crime.
Also in 2005, Major League Baseball (MLB), amid
long-time rumors of anabolic steroid abuse among
players, was rocked by the publication of Juiced by
former Oakland Athletics outfielder Jose Canseco
who alleged steroid abuse was wide-spread in professional baseball. In response, Congress held hearings in
March 2005 on steroid abuse in the MLB, subpoenaing
such baseball superstars as home run champion Mark
McGwire (now retired), Sammy Sosa, and Curt
Schilling to testify. In response, MLB officials promised
a crackdown on anabolic steroid use among players.

In addition to these dangerous side effects, steroid
abuse brings other risks, some of which are connected
to the way some steroids are manufactured and distributed. The drugs are often made in motel rooms and
warehouses in Mexico, Europe, and other countries
and then smuggled into the United States. The
potency, purity, and strength of the steroids produced
this way are not regulated; therefore, users cannot
know how much they are taking. Counterfeit steroids
are also sold as the real thing. So it is often impossible
to tell exactly what some products contain.

It has been estimated that at least one in 15 male
high school seniors in the United States—more than
500,000 boys—has used steroids. Some are athletes
attempting to increase their strength and size; others
are simply youths attempting to speed up their growth
to keep pace with their peers. In some countries, anabolic steroids are available over the counter. In the
United States, a doctor’s prescription is necessary.

Causes and symptoms
While the effects of steroids can seem desirable at
first, there are serious side effects. Excessive use can
cause a harmful imbalance in the body’s normal hormonal balance and body chemistry. Heart attacks,
water retention leading to high blood pressure and
stroke, and liver and kidney tumors all are possible.
Young people may develop acne, sometimes severe,
and a halting of bone growth. Males may experience
shrinking testicles, falling sperm counts, enlarged
176

The psychological effects of steroid use are also
alarming: drastic mood swings, inability to sleep,
depression, and feelings of hostility. Steroids may
also be psychologically addictive. Once started,
users—particularly athletes—enjoy the physical socalled benefits of increased size, strength, and endurance so much that they are reluctant to stop even when
told about the risks.

Most data on the long-term effects of anabolic
steroids on humans come from case reports rather
than formal scientific studies. From the case reports,
the incidence of life-threatening effects appears to be
low, but serious adverse effects may be under-recognized or under-reported. Data from animal studies
seem to support this possibility. One study found
that exposing male mice for one-fifth of their lifespan
to steroid doses comparable to those taken by human
athletes caused a high percentage of premature deaths.
Most effects of anabolic steroid use are reversible if
the abuser stops taking the drugs, but some can be
permanent.

Diagnosis
Anyone who is using anabolic steroids without a
prescription and not under the direction of a physician
is considered abusing the drug and should seek medical help in stopping the use.

Treatment
Few studies of treatments for anabolic steroid
abuse have been conducted. Knowledge as of 2005 is
GALE ENCYCLOPEDIA OF MEDICINE

Some medications that have been used for treating
steroid withdrawal restore the hormonal system after
its disruption by steroid abuse. Other medications target specific withdrawal symptoms, for example, antidepressants to treat depression, and analgesics (pain
killers, such as aspirin and ibuprofen) for headaches
and muscle and joint pains. Some patients require assistance beyond simple treatment of withdrawal symptoms and are treated with behavioral therapies.

Alternative treatment
There is little data on alternative medicines or
treatments for anabolic steroid abuse. However, anabolic steroid manufacturers recommend saw palmetto
to be taken in conjunction with androstenedione as it
can help reduce associated hair loss and is useful in
controlling prostate enlargement.

Prognosis
Anabolic steroid abuse is a treatable condition
and can be stopped. Teenagers and adults can overcome the problem with the help of parents and other
family members, support groups, psychotherapy,
medication, treatment programs, and family counseling. These programs are customized to help teens and
adults lead productive and normal lives. However,
heavy steroid use—even if it is stopped after a few
years—may increase the risk of liver cancer. A steroid
user who quits may suffer a side effect commonly linked
to low testosterone—severe depression—which can
lead to suicidal thoughts and even suicide. The risk of
depression and suicide is highest among teens.
Some physicians recommend that athletes using
steroids avoid sudden discontinuance of all steroids at
the same time because their bodies may enter an
immediate catabolic (sudden release of energy)
phase. The cortisone receptors will be free and in
combination with the low testosterone and androgen
levels, a considerable loss of strength and mass, and an
increase of fat and water, and often breast enlargement in males can occur. Breast enlargement is possible because the suddenly low androgen level shifts the
relationship in favor of the estrogens which suddenly
become the domineering hormone.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
The best prevention is education to alert young
people to the dangers, both medical and legal, in the
illegal use of anabolic steroids. In its effort to alert
teenagers to the dangers of steroid abuse, the U.S.
Food and Drug Administration (FDA) developed a
series of pamphlets, posters, and public service
announcements. Much of this information is available
on-line at <http://www.fda.gov>. Anabolic steroids
are in the same regulatory category as cocaine, heroin,
LSD, and other habit-forming drugs. This means that,
in addition to the FDA, the Drug Enforcement Agency
(DEA) helps to enforce laws relating to their abuse.
Athletic organizations have joined the fight. The
Olympic Games are now closely monitored to prevent
athletes who use steroids from participating. The
National Football League has a strict testing policy
in its training camps; it delivers fines and suspensions
to those who test positive and bans repeat offenders.
The National Collegiate Athletic Association, too, has
established stricter measures for testing and disciplining steroid users.
Resources
BOOKS

Aretha, David. Steroids and Other Performance-Enhancing
Drugs. Berkeley Heights, NJ: MyReportLinks.com,
2005.
Canseco, Jose. Juiced: Wild Times, Rampant ‘Roids, Smash
Hits, and How Baseball Got Big. New York City: Regan
Books, 2005.
Levert, Suzanne. The Facts about Steroids. New York:
Benchmark Books, 2004.
Taylor, William N. Anabolic Therapy in Modern Medicine.
Jefferson, NC: McFarland & Company, 2002.
PERIODICALS

Adler, Jerry. ‘‘Toxic Strength: The Headlines about Illegal
Steroids Have Focused on Professional and Olympic
Athletes. But the Most Vulnerable Users May Be Kids
in Your Neighborhood, High-Schoolers Who Are
Risking an Array of Frightful Side Effects that Can
Lead to Death.’’ Newsweek (December 20, 2004): 44.
Bates, Betsy. ‘‘Elite Athletes Not Alone in Anabolic Steroid
Abuse: Missed by Drug Testing.’’ Internal Medicine
News (February 1, 2004): 38.
Brown, Tim. ‘‘McGwire Appears to Suffer Lasting Damage
to Credibility after Refusing to Discuss Steroids, and
Baseball Will Tinker with Details of Its Drug Policy.’’
Los Angeles Times (March 19, 2005): D–1.
Goodlad, Terry. ‘‘Dancing with the Dark Side: So, You
Think You’re Ready for Your First Steroid Cycle?’’
Flex (April 2004): 90–96.
Ingram, Scott. ‘‘Buff Enough? More Teens Are Using
Steroids to Look Pumped and Do Better at Sports. Do
177

Anabolic steroid use

based largely on the experiences of a small number of
physicians who have worked with patients undergoing
steroid withdrawal. The physicians have found that
supportive therapy is sufficient in some cases. Patients
are educated about what they may experience during
withdrawal and are evaluated for suicidal thoughts. If
symptoms are severe or prolonged, medications or
hospitalization may be needed.

Anaerobic infections

they Know the Terrible Risk They’re Taking?’’ Current
Science (September 24, 2004): 4–8.
Poniewozik, James. ‘‘This Is Your Nation on Steroids: Why
Does a Performance-Enhanced Society Scorn
Performance-Enhanced Athletes?’’ Time (December 20,
2004): 168.

KEY TERMS
Abscess—A lump filled with pus resulting from an
infection.
Anaerobic—Living and growing in the absence of
oxygen.

ORGANIZATIONS

National Center for Drug Free Sport Inc. 810 Baltimore St.,
Kansas City, MO 64105. (816) 474-7329. <http://
www.drugfreesport.com>.
National Institute on Drug Abuse. 6001 Executive Blvd.,
Bethesda, MD 20892. (301)443-1124. <information@lists.nida.nih.gov>. <http://
www.drugabuse.gov>.
OTHER

Drug Enforcement Administration. Steroid Abuse in
Today’s Society, March 2004. [cited March 21, 2005].
<http://www.deadiversion.usdoj.gov/pubs/brochures/
steroids/professionals/professionals.pdf>.
Focus Adolescent Service. Teens and Anabolic Steroids,
2005. [cited March 21, 2005]. <http://www.focusas.com/Steroids.html>.

Ken R. Wells

Necrosis—Tissue death and destruction resulting
from infection or disease.

infection. Body sites that have tissue destruction
(necrosis) or a poor blood supply are low in oxygen
and favor the growth of anaerobic bacteria. The low
oxygen condition can result from blood vessel disease,
shock, injury, and surgery.
Anaerobic bacteria can cause infection practically
anywhere in the body. For example:


Mouth, head, and neck. Infections can occur in the
root canals, gums (gingivitis), jaw, tonsils, throat,
sinuses, and ears.



Lung. Anaerobic bacteria can cause pneumonia, lung
abscesses, infecton of the lining of the lung
(empyema), and dilated lung bronchi (bronchiectasis).



Intraabdominal. Anaerobic infections within the
abdomen include abscess formation, peritonitis, and
appendicitis.



Female genital tract. Anaerobic bacteria can cause
pelvic abscesses, pelvic inflammatory disease, inflammation of the uterine lining (endometritis), and pelvic
infections following abortion, childbirth, and surgery.



Skin and soft tissue. Anaerobic bacteria are common
causes of diabetic skin ulcers, gangrene, destructive
infection of the deep skin and tissues (necrotizing
fascitis), and bite wound infections.



Central nervous system. Anaerobic bacteria can
cause brain and spinal cord abscesses.



Bloodstream. Anaerobic bacteria can be found in the
bloodstream of ill patients (a condition called
bacteremia).

I Anaerobic infections
Definition
An anaerobic infection is an infection caused by
bacteria (called anaerobes) which cannot grow in the
presence of oxygen. Anaerobic bacteria can infect
deep wounds, deep tissues, and internal organs where
there is little oxygen. These infections are characterized by abscess formation, foul-smelling pus, and tissue destruction.

Description
Anaerobic means ‘‘life without air.’’ Anaerobic
bacteria grow in places which completely, or almost
completely, lack oxygen. They are normally found in
the mouth, gastrointestinal tract, and vagina, and on
the skin. Commonly known diseases caused by anaerobic bacteria include gas gangrene, tetanus, and botulism. Nearly all dental infections are caused by
anaerobic bacteria.
Anaerobic bacteria can cause an infection when a
normal barrier (such as skin, gums, or intestinal wall)
is damaged due to surgery, injury, or disease. Usually,
the immune system kills any invading bacteria, but
sometimes the bacteria are able to grow and cause an
178

Causes and symptoms
People who have experienced shock, injury, or
surgery, and those with blood vessel disease or
tumors are at an increased risk for infection by anaerobic bacteria. There are many different kinds of
anaerobic bacteria which can cause an infection.
Indeed, most anaerobic infections are ‘‘mixed infections’’ which means that there is a mixture of different bacteria growing. The anaerobic bacteria that
GALE ENCYCLOPEDIA OF MEDICINE

The signs and symptoms of anaerobic infection can
vary depending on the location of the infection. In general, anaerobic infections result in tissue destruction, an
abscess which drains foul-smelling pus, and possibly
fever. Symptoms for specific infections are as follows:


Tooth and gum infections. Swollen, tender bleeding
gums, bad breath, and pain. Severe infections may
produce oozing sores.



Throat infection. An extremely sore throat, bad
breath, a bad taste in the mouth, fever, and a sense
of choking.



Lung infection. Chest pain, coughing, difficulty breathing, fever, foul-smelling sputum, and weight loss.



Intraabdominal infection. Pain, fever, and possibly,
if following surgery, foul- smelling drainage from the
wound.



Pelvic infection. Foul-smelling pus or blood draining
from the uterus, general or localized pelvic pain,
fever, and chills.



Skin and soft tissue infection. Infected wounds are
red, painful, swollen, and may drain a foul-smelling
pus. Skin infection causes localized swelling, pain,
redness, and possibly a painful, open sore (ulcer)
which drains foul-smelling pus. Severe skin infections
may cause extensive tissue destruction (necrosis).



Bloodstream. Bloodstream invasion causes high
fever (up to 1058F [40.68C]), chills, a general ill feeling, and is potentially fatal.

Diagnosis
The diagnosis of anaerobic infection is based primarily on symptoms, the patient’s medical history,
and location of the infection. A foul-smelling infection
or drainage from an abscess is diagnostic of anaerobic
infection. This foul smell is produced by anaerobic
bacteria and occurs in one third to one half of patients
late in the infection. Other clues to anaerobic infection
include tissue necrosis and gas production at the infection
site. A sample from the infected site may be obtained,
using a swab or a needle and syringe, to determine which
bacteria is (are) causing the infection. Because these bacteria can be easily killed by oxygen, they rarely grow in
the laboratory cultures of tissue or pus samples.
The recent medical history of the patient is helpful
in diagnosing anaerobic infection. A patient who has or
recently had surgery, dental work, tumors, blood vessel
disease, or injury are susceptible to this infection. The
failure to improve following treatment with antibiotics
GALE ENCYCLOPEDIA OF MEDICINE

that aren’t able to kill anaerobes is another clue that
the infection is caused by anaerobes. The location and
type of infection also help in the diagnosis.
Diagnostic tests may include blood tests to see if
bacteria are in the bloodstream and x rays to look at
internal infections.

Treatment
Serious infections may require hospitalization for
treatment. Immediate antibiotic treatment of anaerobic
infections is necessary. Laboratory testing may identify
the bacteria causing the infection and also which antibiotic will work best. Every antibiotic does not work
against all anaerobic bacteria but nearly all anaerobes
are killed by chloramphenicol (Chloromycetin), metronidazole (Flagyl or Protostat), and imipenem
(Primaxin). Other antibiotics which may be used are
clindamycin (Cleocin) or cefoxitin (Mefoxin).
Surgical removal or drainage of the abscess is
almost always required. This may involve drainage
by needle and syringe to remove the pus from a skin
abscess (called ‘‘aspiration’’). The area would be
numbed prior to the aspiration procedure. Also,
some internal abscesses can be drained using this
procedure with the help of ultrasound (a device
which uses sound waves to visualize internal organs).
This type of abscess drainage may be performed in
the doctor’s office.

Prognosis
Complete recovery should be achieved with the
appropriate surgery and antibiotic treatment.
Untreated or uncontrolled infections can cause severe
tissue and bone destruction, which would require plastic surgery to repair. Serious infections can be life
threatening.

Prevention
Although anaerobic infections can occur in anyone, good hygiene and general health may help to
prevent infections.
Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

Belinda Rowland, PhD

Anaerobic myositis see Gangrene
179

Anaerobic infections

most frequently cause infections are Bacteroides
fragilis, Peptostreptococcus, and Clostridium species.

Anal atresia

I Anal atresia
Definition
The anus is either not present or it is in the wrong
place.

Description
There are basically two kinds of anal atresia. In
boys with high anal atresia, there may be a channel
(fistula) connecting the large intestine to either the
urethra (which delivers urine from the bladder) or
the bladder itself. In girls, the channel may connect
with the vagina. Sixty percent of children with high
anal atresia have other defects, including problems
with the esophagus, urinary tract, and bones. In low
anal atresia, the channel may open in front of the
circular mass of muscles that constrict to close the
anal opening (anal sphincter) or, in boys, below
the scrotum. Occasionally, the intestine ends just
under the skin. It is estimated that overall abnormalities of the anus and rectum occur in about one in every
5,000 births and are slightly more common among
boys. A mother who has one child with these kind of
conditions has a 1% chance of having another child
who suffers from this ailment.

Causes and symptoms
Anal atresia is a defect in the development of the
fetus. The cause is unknown, but genetics seem to play
a minor role.

KEY TERMS
Anus—The canal at the end of the large intestine
through which waste is excreted to the outside of
the body.
Bowel obstruction—Anything that prevents waste
from moving normally to the anal opening.
Colostomy—An operation where the large intestine is diverted through an opening in the abdomen
and waste is excreted.
Feces—Bodily waste material that normally passes
through the anus.
Fistula—An abnormal channel that connects two
organs or connects an organ to the skin.

made, a surgical incision is made in the large intestine
to make a temporary opening (colostomy) in the abdomen where waste is excreted. Several months later, the
intestine is moved into the ring of muscle (sphincter)
that is part of the anus and a hole is made in the skin.
The colostomy is closed several weeks later. In low anal
atresia, immediately after diagnosis, a hole is made in
the skin to open the area where the anus should be. If
the channel is in the wrong place, the intestine is
moved into the correct position sometime during the
child’s first year. After surgery, the pediatric surgeon
uses an instrument to dilate or widen the rectum and
teaches the parents how to do this daily at home to
prevent scar tissue from contracting.

Diagnosis
Usually a physician can make an obvious visual
diagnosis of anal atesia right after birth. Occasionally,
however, anal atresia is missed until the baby is fed and
signs of intestinal obstruction appear. At the end of the
first or second day, the abdomen swells and there is
vomiting of fecal material. To determine the type of
anal atresia and the exact position, x rays will be taken
which include injecting opaque dye into the opening.
Magnetic resonance imaging (MRI) or computed tomography scans (CT), as well as ultrasound, are the imaging techniques used to determine the type and size of
the anal atresia. Ultrasound uses sound waves, CT
scans pass x rays through the body at different angles,
and an MRI uses a magnetic field and radio waves.

Treatment
Surgery is the only treatment for anal atresia. For
high anal atresia, immediately after the diagnosis is
180

Prognosis
With high anal atresia, many children have problems controlling bowel function. Most also become
constipated. With low anal atresia, children generally
have good bowel control, but they may still become
constipated.

Prevention
There is no known way to prevent anal atresia.
Resources
BOOKS

Paidas, Charles N., and Alberto Pena. ‘‘Rectum and Anus.’’
In Surgery of Infants and Children. Philadelphia:
Lippincott-Raven, 1997.

Jeanine Barone, Physiologist
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Anal cancer is an uncommon form of cancer
affecting the anus. The anus is the inch-and-a-halflong end portion of the large intestine, which opens
to allow solid wastes to exit the body. Other parts of
the large intestine include the colon and the rectum.

Description
Different cancers can develop in different parts of
the anus, part of which is inside the body and part of
which is outside. Sometimes abnormal changes of the
anus are harmless in their early stages but may later
develop into cancer. Some anal warts, for example,
contain precancerous areas and can develop into cancer. Types of anal cancer include:

KEY TERMS
Biopsy—A procedure in which a small piece of
body tissue is removed and examined under a
microscope for cancer.
Chemotherapy—A cancer treatment in which drugs
delivered into the blood stream kill cancer cells or
make them more vulnerable to radiation therapy.
Human papillomavirus (HPV)—A virus with many
subtypes, some of which cause cell changes that
increase the risk of certain cancers.
Human immunodeficiency virus (HIV)—The virus
that causes acquired immune deficiency syndrome
(AIDS).
Lymph nodes—Bean-shaped structures found
throughout the body that produce and store
infection-fighting cells.

Squamous Cell Carcinomas. Approximately half of
anal cancers are squamous cell carcinomas, which
arise from the cells lining the anal margin and the
anal canal. The anal margin is the part of the anus
that is half inside and half outside the body, and the
anal canal is the part of the anus that is inside the
body. The earliest form of squamous cell carcinoma
is known as carcinoma in situ, or Bowen’s disease.

Radiation therapy—A cancer treatment that uses
high-energy rays to kill or weaken cancer cells.
Radiation may be delivered externally or internally
via surgically implanted pellets.



Cloacogenic Carcinomas. Approximately onefourth to one-third of anal tumors are cloacogenic
carcinomas. These tumors develop in the transitional
zone, or cloaca, which is a ring of tissue between the
anal canal and the rectum.



Adenocarcinomas. About 15% of anal cancers are
adenocarcinomas, which affect glands in the anal
area. One type of adenocarcinoma that can occur in
the anal area is called Paget’s disease, which can also
affect the vulva, breasts, and other areas of the body.



Skin cancers. A small percentage of anal cancers are
either basal cell carcinomas, or malignant melanomas, two types of skin cancer. Malignant melanomas, which develop from skin cells that produce the
brown pigment called melanin, are far more common
on areas of the body exposed to the sun.

The exact cause of most anal cancers is unknown,
although certain individuals appear to have a higher
risk of developing the disease. Smokers are at higher
risk, as are individuals with certain types of the human
papillomavirus (HPV), and those with long-term problems in the anal area, such as abnormal openings
known as fistulas. Since it increases the risk of HPV
infection, the practice of anal sex appears to increase
the risk of anal cancer—male homosexuals who practice anal sex are about 33 times more likely to have
anal cancers than heterosexual men. Those with weakened immune systems, such individuals with HIV, or
transplant patients taking immunosuppressant drugs,
are also at higher risk. Most individuals with anal
cancer are over the age of 50.



Approximately 3,500 Americans will be diagnosed with anal cancer in 2001, and an estimated 500
individuals will die of the disease during this same
interval, according to the American Cancer Society.
Anal cancers are fairly rare: they make up only 1% to
2% of cancers affecting the digestive system. The disease affects women somewhat more often than men,
although the number of cases among men, particularly
homosexual men, seems to be increasing.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms

Symptoms of anal cancer resemble those found in
other harmless conditions. They include pain, itching
and bleeding, straining during a bowel movement,
change in bowel habits, change in the diameter of the
stool, discharge from the anus, and swollen lymph
nodes in the anal or groin area.

Diagnosis
Anal cancer is sometimes diagnosed during routine physicals, or during minor procedures such as
181

Anal cancer

I Anal cancer

Anal cancer

hemorrhoid removal. It may also be diagnosed during
a digital rectal examination (DRE), when a physician
inserts a gloved, lubricated finger into the anus to
feel for unusual growths. Individuals over the age of
50 who have no symptoms should have a digital rectal
examination (DRE) every five to 10 years, according
to American Cancer Society (ACS) guidelines for early
detection of colorectal cancer.
Other diagnostic procedures for anal cancer
include: Anoscopy. A procedure that involves use of a
special device to examine the anus. Proctoscopy. A
procedure that involves use of a lighted scope to see
the anal canal. Transrectal ultrasound. A procedure in
which sound waves are used to create an image of the
anus and nearby tissues.
A biopsy is performed on any suspicious growths;
that is, a tiny piece of the growth is examined under a
microscope for cancer cells. The physician may also
perform a procedure called a fine needle aspiration
biopsy, in which a needle is used to withdraw fluid
from lymph nodes located near the growth, to make
sure the cancer has not spread to these nodes.
Anal cancer severity is categorized by the following stages:


Stage 0 anal cancer is found only in the top layer of
anal tissue.



Stage I anal cancer has spread beyond the top layer
of anal tissue, but is less than 1 inch in diameter.



Stage II anal cancer has spread beyond the top layer
of anal tissue and is larger than 1 inch in diameter,
but has not spread to nearby organs or lymph nodes.



Stage IIIA anal cancer has spread to the lymph nodes
around the rectum or to nearby organs such as the
vagina or bladder.





Stage IIIB anal cancer has spread to lymph nodes in
the mid-abdomen or groin, or to nearby organs and
the lymph nodes around the rectum.
Stage IV anal cancer has spread to distant lymph
nodes within the abdomen or to distantorgans.

Treatment
Anal cancer is treated using three methods, used
either in concert or individually: surgery, radiation
therapy, and chemotherapy.
Two types of surgery may be performed. A local
resection, performed if the cancer has not spread,
removes the tumor and an area of tissue around
the tumor. An abdominoperineal resection is a more
complex procedure in which the anus and the lower
182

rectum are removed, and an opening called a colostomy is created for body wastes to exit. This procedure
is fairly uncommon today because radiation and
chemotherapy are just as effective.
Chemotherapy fights cancer using drugs, which
may be delivered via pill or needle. Some chemotherapy types kill cancer cells directly, while others act
indirectly by making cancer cells more vulnerable to
radiation. The main drugs used to treat anal cancer
are 5-fluorouracil (5-FU) and mitomycin or 5-FU
and cisplatin. Side effects of chemotherapy, which
damages normal cells in addition to cancer cells, may
include nausea and vomiting, hair loss, loss of appetite,
diarrhea, mouth sores, fatigue, shortness of breath,
and a weakened immune system.

Alternative treatment
Research suggests acupuncture can help manage
chemotherapy-related nausea and vomiting and control pain associated with surgery.

Prognosis
Anal cancer is often curable. The chance of recovery
depends on the cancer stage and the patient’s general
health.

Prevention
Reducing the risks of the sexually transmitted diseases HPV and HIV also reduces the risk of anal
cancer. In addition, quitting smoking lowers the risk
of anal cancer.
Resources
PERIODICALS

Murakami, M, K. J. Gurski, and M. A. Steller
‘‘Human Papillomavirus Vaccines For Cervical Cancer.’’
Journal of Immunotherapy 22, no. 3 (1999): 212-8.
ORGANIZATIONS

American Cancer Society 1599 Clifton Road, NE, Atlanta,
GA 30329. (404) 320-3333 or (800) ACS-2345. Fax:
(404) 329-7530. <http://www.cancer.org>.
American College of Gastroenterology. 4900 B South 31st
St., Arlington, VA 22206-1656. (703) 820-7400.
<http://www.acg.gi.org>.
American Gastroenterological Association. 7910
Woodmont Ave., Seventh Floor, Bethesda, MD 20814.
(301) 654-2055. <http://www.gastro.org>.
American Society of Colon and Rectal Surgeons. 85 W.
Algonquin Road, Suite 550, Arlington Heights, Illinois
60005. (847) 290-9184.
GALE ENCYCLOPEDIA OF MEDICINE

Ann Quigley

Anal fissure see Anorectal disorders

KEY TERMS
Electrocoagulation—a technique using electrical
energy to destroy the warts. Usually done for warts
within the anus with a local anesthesia, electrocoagulation is most painful form of therapy, and can
cause both bleeding and discharge from the anus.

direct sexual contact with someone who is infected with
condyloma acuminata anywhere in the genital area,
including the penis and vagina. Studies have shown
that roughly 75% of those who engage in sexual contact with someone infected with condyloma acuminata
will develop these warts within three months.

Treatment

I Anal warts
Definition
Anal warts, also known as condyloma acuminata,
are small warts that can occur in the rectum.

Description
Initially appear as tiny blemishes that can be as
small as the head of a pin or grow into larger cauliflower-like protuberances. They can be yellow, pink,
or light brown in color, and only rarely are painful or
uncomfortable. In fact, infected individuals often are
unaware that they exist. Most cases are caused by
sexual transmission.
Most individuals have between one to 10 genital
warts thtat range in size from roughly 0.5–1.9 cm2.
Some will complain of painless bumps or itching, but
often, these warts can remain completely unnoticed.

Causes and symptoms
Condyloma acuminatum is one of the most common sexually transmitted disease (STD) in the United
States. Young adults aged 17 to 33 years are at greatest
risk. Risk factors include smoking, using oral contraceptives, having multiple sexual partners, and an early
coital age. In addition, individuals who have a history of
immunosuppression or anal intercourse are also at risk.
Roughly 90% of all anal warts are caused by the
human papilloma virus (HPV) types 6 and 11, which
are the least likely of over 60 types of HPV to become
cancerous. Anal warts are usually transmitted through
GALE ENCYCLOPEDIA OF MEDICINE

According to guidelines from the Centers for Disease
Control (CDC), the treatment of all genital warts, including anal warts, should be conducted according to the
methods preferred by the patient, the medications or
procedures most readily available, and the experience
of the patient’s physician in removing anal warts.
Treatment options include electrical cautery, surgical removal, or both. Warts that appear inside the
anal canal will almost always be treated with cauterization or surgical removal. Surgical removal, also
known as excision, has the highest success rates and
lowest recurrence rates. Indeed, studies have shown
that initial cure rates range from 63–91%.
Unfortunately, most cases require numerous
treatments because the virus that causes the warts
can live in the surrounding tissue. The area may seem
normal and wart-free for six months or longer before
another wart develops.
Electrocoagulation, a technique that uses electrical energy to destroy the warts, is usually the most
painful of the procedures done to eliminate condyloma acuminata of the anus, and is usually reserved
for larger warts. It is done with local anesthesia, and
may cause discharge or bleeding from the anus.
Follow-up visits to the physician are necessary to
make sure that the warts have not recurred. It is
recommended that these patients see their physicians
every three to six months for up to 1.5 years, which is
how long the incubation period is for the HPV virus.
Carbon dioxide laser treatment and electrodesiccation are other options, but these are usually reserved for
extensive warts or those that continue to recur despite
numerous treatments. However, because HPV virus can
183

Anal warts

National Cancer Institute (National Institutes of Health).
9000 Rockville Pike, Bethesda, MD 20892. (800) 4226237. <http://www.nci.nih.gov>.
National Coalition for Cancer Survivorship. 1010 Wayne
Avenue, 5th Floor, Suite 300, Silver Spring, MD 20910.
(888) 650-9127.
NCI Office of Cancer Complementary and Alternative
Medicine. <http://occam.nci.nih.gov>.
NIH National Center for Complementary and Alternative
Medicine. Post Office Box 8218, Silver Spring, MD
20907-8218. (888) 644-6226. <http://nccam.nih.gov>.
United Ostomy Association. (800) 826-0826. <http://
www.uoa.org>.

Analgesics

be transmitted via the smoke caused by these procedures, they are usually reserved for the worst infections.
For small warts that affect only the skin around
the anus, several medications are available, which can
be applied directly to the surface of the warts by a
physician or by the patients themselves.
Such medications include podophyllum resin
(Podocon-25, Pod-Ben-25), a substance made from
the cytotoxic extracts of several plants. This agent
offers a cure rate of 20–50% when used alone, and is
applied by the physician weekly and then washed off
6 hours later by the patient.
Podofilox (Condylox) is another agent, and is
available for patients to use at home. It can be applied
twice daily for up to 4 weeks. Podofilox offers a
slightly higher cure rate than podophyllin, and can
also be used to prevent warts.
Trichloroacetic and bichloroacetic acids are available in several concentrations up to 80% for the treatment of condyloma acuminata. These acids work to
cauterize the skin, and are quite caustic. Nevertheless,
they cause less irritation and overall body effects than
the other agents mentioned above. Recurrence, however, is higher with these acids.
Bleomycin (Blenoxane) is another treatment
option, but it has several drawbacks. First, it must be
administered by a physician into each lesion via injection, but is can have a host of side effects, and patients
must be followed carefully by their physician.
Imiquimod 5% cream is also available for patients
to apply themselves. It is to be applied three times
weekly, for up to 16 weeks, and has been shown to
clear warts within eight to 10 weeks.
Finally, the interferon drugs, which are naturally
occurring proteins that have antiviral and antitumor
effects, are available. These include interferon alfa 2a
and 2b (Roferon, Intron A), which are to be injected
into each lesion twice a week for up to eight weeks.

of HPV (up to 1.5 years), deep lesions, undetected lesions,
virus present in surrounding skin that is not treated.

Prevention
Sexual abstinence and monogamous relationships
can be the most effective form of prevention, and
condoms may also decrease the chances of transmission of condyloma acuminata. Abstinence from sexual
relations with people who have anal or genital warts
can prevent infection. Unfortunately, since many people may not be aware that they have this condition,
this is not always possible.
Individuals infected with anal warts should have
follow-up checkups every few weeks after their initial
treatment, after which self-exams can be done.
Sexual partners of people who have anal warts
should also be examined, as a precautionary preventive measure.
Finally, 5-flourouracil (Adrucil, Efudex, Fluoroplex) may be useful to prevent recurrence once the
warts have been removed. Treatment must, however,
be initiated within 1 month of wart removal.
Resources
PERIODICALS

Maw, Raymond, and Geo von Krogh. ‘‘The Management of
Anal Warts.’’ British Medical Journal no. 321 (October
14, 2000): 910-11.
ORGANIZATIONS

Centers for Disease Control and Prevention. Sexually
Transmitted Diseases Hotline: (800) 227-8922.
OTHER

<http://www.arthritis-baldness-impotency-obesity.com/
medcenter/NF009.html>.
<http://www.emedicine.com>.
<http://www.mayohealth.org>.
<http://wwwmedlineplus.adam.com>.

Liz Meszaros

Prognosis
Once a diagnosis of anal warts has been made,
further outbreaks can be controlled or sometimes prevented with proper care. Unfortunately, many cases of
anal warts either fail to respond to treatment or recur.
Patients have to undergo roughly six to nine treatments over several months to assure that the warts
are completely eradicated.
Recurrence rates have been estimated to be over
50% after one year and may be due to the long incubation
184

I Analgesics
Definition
Analgesics are medicines that relieve pain.

Purpose
Analgesics are those drugs that mainly provide
pain relief. The primary classes of analgesics are the
GALE ENCYCLOPEDIA OF MEDICINE

Description
Pain has been classified as ‘‘productive’’ pain and
‘‘non-productive’’ pain. While this distinction has
no physiologic meaning, it may serve as a guide to
treatment. ‘‘Productive’’ pain has been described as a
warning of injury, and so may be both an indication of
need for treatment and a guide to diagnosis. ‘‘Nonproductive’’ pain by definition serves no purpose
either as a warning or diagnostic tool.
Although pain syndromes may be dissimilar, the
common factor is a sensory pathway from the affected
organ to the brain. Analgesics work at the level of the
nerves, either by blocking the signal from the peripheral nervous system, or by distorting the interpretation
by the central nervous system. Selection of an appropriate analgesic is based on consideration of the riskbenefit factors of each class of drugs, based on type of
pain, severity of pain, and risk of adverse effects.
Traditionally, pain has been divided into two classes,
acute and chronic, although severity and projected
patient survival are other factors that must be considered in drug selection.
Acute pain
Acute pain is self limiting in duration, and
includes post-operative pain, pain of injury, and childbirth. Because pain of these types is expected to be
short term, the long-term side effects of analgesic therapy may routinely be ignored. Thus, these patients
may safely be treated with narcotic analgesics without
concern about possible addiction, or NSAIDs with
only limited concern for the risk of ulcers. Drugs and
doses should be adjusted based on observation of
healing rate, switching patients from high to low
doses, and from narcotic analgesics to non-narcotics
when circumstances permit.
An important consideration of pain management
in severe pain is that patients should not be subject to
the return of pain. Analgesics should be dosed
adequately to ensure that the pain is at least tolerable,
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Acute pain—Pain that is usually temporary and
results from something specific, such as a surgery,
an injury, or an infection.
Analgesic—Medicine used to relieve pain.
Chronic pain—Pain that lasts more than three
months and threatens to disrupt daily life.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Osteoarthritis—Joint pain resulting from damage
to the cartilage.

and frequently enough to avoid the anxiety that
accompanies the anticipated return of pain.
Analgesics should never be dosed on an as needed
basis, but should be administered often enough to
assure constant blood levels of analgesic. This applies
to both the narcotic and non-narcotic analgesics.
Chronic pain
Chronic pain, pain lasting over three months and
severe enough to impair function, is more difficult to
treat, since the anticipated side effects of the analgesics
are more difficult to manage. In the case of narcotic
analgesics this means the addiction potential, as well
as respiratory depression and constipation. For the
NSAIDs, the risk of gastric ulcers limit dose. While
some classes of drugs, such as the narcotic agonist/
antagonist drugs bupronophine, nalbuphine and pentazocine, and the selective COX-2 inhibitors celecoxib and
rofecoxib represent advances in reduction of adverse
effects, they are still not fully suitable for long-term
management of severe pain. Generally, chronic pain
management requires a combination of drug therapy,
life-style modification, and other treatment modalities.
Narcotic analgesics
The narcotic analgesics, also termed opioids, are
all derived from opium. The class includes morphine,
codeine, and a number of semi-synthetics including
meperidine (Demerol), propoxyphen (Darvon) and
others. The narcotic analgesics vary in potency, but all
are effective in treatment of visceral pain when used
in adequate doses. Adverse effects are dose related.
Because these drugs are all addictive, they are controlled
under federal and state laws. A variety of dosage forms
are available, including oral solids, liquids, intravenous
and intrathecal injections, and transcutaneous patches.
185

Analgesics

narcotics, including additional agents that are chemically based on the morphine molecule but have minimal abuse potential; nonsteroidal anti-inflammatory
drugs (NSAIDs) including the salicylates; and acetaminophen. Other drugs, notably the tricyclic antidepressants and anti-epileptic agents such as gabapentin, have
been used to relieve pain, particularly neurologic pain,
but are not routinely classified as analgesics. Analgesics
provide symptomatic relief, but have no effect on the
cause, although clearly the NSAIDs, by virtue of their
dual activity, may be beneficial in both regards.

Analgesics, opioid

NSAIDs are effective analgesics even at doses too
low to have any anti-inflammatory effects. There are a
number of chemical classes, but all have similar therapeutic effects and side effects. Most are appropriate
only for oral administration; however ketorolac
(Toradol) is appropriate for injection and may be
used in moderate to severe pain for short periods.
Acetaminophen is a non-narcotic analgesic with no
anti-inflammatory properties. It is appropriate for mild
to moderate pain. Although the drug is well tolerated in
normal doses, it may have significant toxicity at high
doses. Because acetaminophen is largely free of side
effects at therapeutic doses, it has been considered the
first choice for mild pain, including that of osteoarthritis.
Topical analgesics (topical being those that are
applied on the skin) have become much more popular
in recent years. Those applied for local effect include
capsaicin, methylsalicylate, and transdermal lidocaine.
Transdermal fentanyl may be applied for systemic (the
entire body in general) effect. In some cases, these
topical agents reduce the need for drug therapy. Sales
of pain relief patches have increased substantially in
recent years. They are particularly useful for elderly
patients who may not want to take a lot of tablets.

Recommended dosage
Appropriate dosage varies by drug, and should
consider the type of pain, as well as other risks associated with patient age and condition. For example,
narcotic analgesics should usually be avoided in
patients with a history of substance abuse, but may be
fully appropriate in patients with cancer pain. Similarly,
because narcotics are more rapidly metabolized in
patients who have used these drugs for a long period,
higher than normal doses may be needed to provide
adequate pain management. NSAIDs, although comparatively safe in adults, represent an increased risk of
gastrointestinal bleeding in patients over the age of 60.

Precautions
Narcotic analgesics may be contraindicated in
patients with respiratory depression. NSAIDS may
be hazardous to patients with ulcers or an ulcer history. They should be used with care in patients with
renal insufficiency or coagulation disorders. NSAIDs
are contraindicated in patients allergic to aspirin.

The primary adverse effects of the narcotic
analgesics are addiction, constipation, and respiratory depression. Because narcotic analgesics stimulate the production of enzymes that cause the
metabolism of these drugs, patients on narcotics for
a prolonged period may require increasing doses.
This is not the same thing as addiction, and is not a
reason for withholding medication from patients in
severe pain.
NSAIDs can lead to ulcers and may cause kidney problems. Gastrointestinal discomfort is common, although in some cases, these drugs may
cause ulcers without the prior warning of gastrointestinal distress. Platelet aggregation problems may
occur, although not to the same extent as is seen
with aspirin.

Interactions
Interactions depend on the specific type of
analgesic.
Resources
PERIODICALS

‘‘Analgesics: No Pain, No Gain.’’ Chemist & Druggist
(September 11, 2004): 38.
Kuritzky, Louis.‘‘Topical Capsaicin for Chronic Pain.’’
Internal Medicine Alert (September 29, 2004): 144.
‘‘Pain Relief Patches Are Flying Off Store Shelves.’’ Chain
Drug Review (August 16, 2004): 15.

Samuel D. Uretsky, PharmD
Teresa G. Odle

I Analgesics, opioid
Definition
Opioid analgesics, also known as narcotic analgesics, are pain relievers that act on the central nervous
system. Like all narcotics, they may become habitforming if used over long periods.

Purpose
Side effects
Each drug’s adverse effects should be reviewed
individually. Drugs within a class may vary in their
frequency and severity of adverse effects.
186

Opioid analgesics are used to relieve pain from a
variety of conditions. Some are used before or during
surgery (including dental surgery) both to relieve pain
and to make anesthetics work more effectively. They
GALE ENCYCLOPEDIA OF MEDICINE

Drug

Route of
administration

Onset of
action (min)

Time to peak
effect (min)

Duration of
action (h)

IM
IV
Oral
IM
IV
Sub-Q
Oral
IM
IV
Sub-Q
Oral
IM
IV
Sub-Q
Oral
IM
IV
Oral
IM
IV
Sub-Q
Epidural
IM
IV
Sub-Q
Rectal

7–15
1–2
30
15
10–15
30
10–60

20–30
3–5
90–120

1–2
0.5–1
4

30–60

2–3
15–30
4–5

Strong agonists
Fentanyl (Sublimaze)
Hydromorphone (Dilaudid)

Levorphanol (Levo-Dromoran)

Meperidine (Demerol)

Methadone (Dolophine)

Morphine (many trade names)

Oxymorphone (Numorphan)

—
10–60
15
10–15
1
30–60
10–20
—
10–30

90–120
60
within 20
60–90

4–5
2–4

30–50

2–4

90–120

4–6

60–120
60–120

4–5
4–5

30–60

4–5

—
10–30
10–15

20
30–90

4–5
3–6

5–10

15–30

3–4

30–40
10–30
10–30
10–30
—
15–60
10–30
2–3
within 15
2–3
within 15
15–30
15–20
2–3
15–20

60–120
30–60

4
4
4
4–6
3–4
4–6
3–4
2–4
3–6
3–4
3–6
3
2–3
2–3
2–3

Mild-to-moderate agonists
Codiene (many trade names)

Hydrocodone (Hycodan)
Oxycodone (Percodan)
Propoxyphene (Darvon, Dolene)
Butophanol (Stadol)
Nalbuphine (Nubian)

Pentazocine (Talwin)

Oral
IM
Sub-Q
Oral
Oral
Oral
IM
IV
IM
IV
Sub-Q
Oral
IM
IV
Sub-Q

30–60
60
120
30–60
30
60
30
—
60–90
30–60
15–30
30–60

may also be used for the same purposes during labor
and delivery.

dizziness, breathing problems, and physical or mental
dependence.

Opioids are also given to relieve the pain of terminal
cancer, diabetic neuropathy, lower back pain, and other
chronic diseases or disorders. The World Health
Organization (WHO) has established a three-stage
‘‘ladder’’ for the use of opioids in managing cancer pain.

Among the drugs in this category are codeine,
propoxyphene (Darvon), propoxyphene and acetaminophen (Darvocet N), meperidine (Demerol), hydromorphone (Dilaudid), morphine, oxycodone,
oxycodone and acetaminophen (Percocet, Roxicet),
and hydrocodone and acetaminophen (Lortab,
Anexsia). These drugs come in many forms—tablets,
syrups, suppositories, and injections, and are sold only
by prescription. For some, a new prescription is
required for each new supply—refills are prohibited
according to federal regulations.

Description
Opioid analgesics relieve pain by acting directly
on the central nervous system. However, this can also
lead to unwanted side effects, such as drowsiness,
GALE ENCYCLOPEDIA OF MEDICINE

187

Analgesics, opioid

Opioid analgesics

Analgesics, opioid

KEY TERMS
Analgesic—Medicine used to relieve pain.
Central nervous system—The brain and spinal cord.
Colitis—Inflammation of the colon (large bowel)
Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Narcotic—A drug derived from opium or compounds similar to opium. Such drugs are potent
pain relievers and can affect mood and behavior.
Long-term use of narcotics can lead to dependence
and tolerance.
Tolerance—A decrease in sensitivity to a drug.
When tolerance occurs, a person must take more
and more of the drug to get the same effect.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug to which he or she has
become dependent.

Recommended dosage
Recommended doses vary, depending on the type of
opioid analgesic and the form in which it is being used.
Doses may be different for different patients. Check with
the physician who prescribed the drug or the pharmacist who filled the prescription for correct dosages, and
make sure to understand how to take the drug.
Always take opioid analgesics exactly as directed.
Never take larger or more frequent doses, and do not
take the drug for longer than directed. Do not stop
taking the drug suddenly without checking with the
physician or dentist who prescribed it. Gradually
tapering the dose may the chance of withdrawal
symptoms.

Precautions
Anyone who uses opioid analgesics—or any narcotic—over a long time may become physically or
mentally dependent on the drug. Physical dependence
may lead to withdrawal symptoms when the person
stops taking the medicine. Building tolerance to these
drugs is also possible when they are used for a long
period. Over time, the body needs larger and larger
doses to relieve pain.
188

Take these drugs exactly as directed. Never take
more than the recommended dose, and do not take the
drugs more often than directed. If the drugs do not
seem to be working, consult your physician. Do not
share these or any other prescription drugs with others
because the drug may have a completely different
effect on the person for whom it was not prescribed.
Children and older people are especially sensitive
to opioid analgesics and may have serious breathing
problems after taking them. Children may also
become unusually restless or agitated when given
these drugs.
Opioid analgesics increase the effects of alcohol.
Anyone taking these drugs should not drink alcoholic
beverages.
Some of these drugs may also contain aspirin,
caffeine, or acetaminophen. Refer to the entries on
each of these drugs for additional precautions.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if they
take opioid analgesics. Before taking these drugs, be sure
to let the physician know about any of these conditions.
ALLERGIES. Let the physician know about any allergies to foods, dyes, preservatives, or other substances
and about any previous reactions to opioid analgesics.
PREGNANCY. Women who are pregnant or plan
to become pregnant while taking opioid analgesics
should let their physicians know. No evidence exists
that these drugs cause birth defects in people, but some
do cause birth defects and other problems when given to
pregnant animals in experiments. Babies can become
dependent on opioid analgesics if their mothers use
too much during pregnancy. This can cause the baby
to go through withdrawal symptoms after birth. If
taken just before delivery, some opioid analgesics
may cause serious breathing problems in the newborn.
BREAST FEEDING. Some opioid analgesics can pass
into breast milk. Women who are breast feeding
should check with their physicians about the safety
of taking these drugs.
OTHER MEDICAL CONDITIONS. These conditions
may influence the effects of opioid analgesics:


head injury. The effects of some opioid analgesics
may be stronger and may interfere with recovery in
people with head injuries.



history of convulsions. Some of these drugs may
trigger convulsions.



asthma, emphysema, or any chronic lung disease
GALE ENCYCLOPEDIA OF MEDICINE

heart disease



restlessness or nervousness



kidney disease



nightmares, unusual dreams, or problems sleeping



liver disease



weakness or tiredness



HIV infection. Patients undergoing highly active
antiretroviral therapy, or HAART, are at increased
risk for adverse effects from opioid analgesics.



mental sluggishness



stomach pain or cramps



blurred or double vision or other vision problems



problems urinating, such as pain, difficulty urinating, frequent urge to urinate, or decreased amount of
urine



constipation.



underactive thyroid. The chance of side effects may
be greater.



Addison’s disease (a disease of the adrenal glands)



colitis



gallbladder disease or gallstones. Side effects can be
dangerous in people with these conditions.



enlarged prostate or other urinary problems



current or past alcohol abuse

Other side effects may be more serious and may
require quick medical attention. These symptoms
could be signs of an overdose. Get emergency medical
care immediately.



current or past drug abuse, especially narcotic abuse



cold, clammy skin



current or past emotional problems. The chance of
side effects may be greater.



bluish discoloration of the skin



extremely small pupils



serious difficulty breathing or extremely slow
breathing



extreme sleepiness or unresponsiveness



severe weakness



confusion



severe dizziness



severe drowsiness



slow heartbeat



low blood pressure



severe nervousness or restlessness

USE OF CERTAIN MEDICINES. Taking opioid narco-

tics with certain other drugs may increase the chances
of serious side effects.

Side effects
Some people experience drowsiness, dizziness,
lightheadedness, or a false sense of well-being after
taking opioid analgesics. Anyone who takes these
drugs should not drive, use machines, or do anything
else that might be dangerous until they know how the
drug affects them. Nausea and vomiting are common
side effects, especially when first beginning to take the
medicine. If these symptoms do not go away after the
first few doses, check with the physician or dentist who
prescribed the medicine.
Dry mouth is another common side effect. Dry
mouth can be relieved by sucking on sugarless hard
candy or ice chips or by chewing sugarless gum. Saliva
substitutes, which come in liquid or tablet forms, also
may help. Patients who must use opioid analgesics
over long periods and who have dry mouth should
see their dentists, as the problem can lead to tooth
decay and other dental problems.
The following side effects are less common. They
usually do not need medical attention and will go away
after the first few doses. If they continue or interfere
with normal activity, check with the physician who
prescribed the medicine.


headache



loss of appetite

GALE ENCYCLOPEDIA OF MEDICINE

In addition, these less common side effects do
not require emergency medical care, but should have
medical attention as soon as possible:


hallucinations or a sense of unreality



depression or other mood changes



ringing or buzzing in the ears



pounding or unusually fast heartbeat



itching, hives, or rash



facial swelling



trembling or twitching



dark urine, pale stools, or yellow eyes or skin (after
taking propoxyphene)



increased sweating, red or flushed face (more common after taking hydrocodone and meperidine)
189

Analgesics, opioid



Anaphylaxis

Interactions
Anyone taking these drugs should notify his or her
physician before taking opioid analgesics:


Central nervous system (CNS) depressants, such as
antihistamines and other medicines for allergies, hay
fever, or colds; tranquilizers; some other prescription
pain relievers; seizure medicines; muscle relaxants;
sleeping pills; some anesthetics (including dental
anesthetics).



Monoamine oxidase (MAO) inhibitors, such as phenelzine (Nardil) and tranylcypromine (Parnate). The
combination of the opioid analgesic meperidine
(Demerol) and MAO inhibitors is especially
dangerous.



Tricyclic antidepressants, such as amitriptyline
(Elavil).



Anti-seizure medicines, such as carbamazepine
(Tegretol). May lead to serious side effects, including
coma, when combined with propoxyphene and acetaminophen
(Darvocet-N)
or
propoxyphene
(Darvon).



Muscle relaxants, such as cyclobenzaprine (Flexeril).



Sleeping pills, such as triazolam (Halcion).



Blood-thinning drugs, such as warfarin (Coumadin).



Naltrexone (Trexan, Revia). Cancels the effects of
opioid analgesics.



Rifampin (Rifadin).



Zidovudine (AZT, Retrovir). Serious side effects
when combined with morphine.

Opioids may also interact with certain herbal preparations sold as dietary supplements. Among the
herbs known to interact with opioids are valerian
(Valeriana officinalis), ginseng (Panax ginseng), kava
kava (Piper methysticum), and chamomile (Matricaria
chamomilla). As of early 2004 the National Center for
Complementary and Alternative Medicine (NCCAM)
is beginning a study of the possible interactions
between St. John’s wort (Hypericum perforatum, a
herb frequently used to relieve symptoms of depression, and the opioid analgesics fentanyl and oxycodone. It is just as important for patients to inform their
doctor of herbal remedies that they take on a regular
basis as it is to give the doctor a list of their other
prescription medications.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Pain.’’ Section 14, Chapter 167 In The Merck Manual
190

of Diagnosis and Therapy. Whitehouse Station, NJ:
Merck Research Laboratories, 2002.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine,
Part I: Western Herbal Medicine. New York: Simon
and Schuster, 2002.
Wilson, Billie Ann, RN, PhD, Carolyn L. Stang, PharmD,
and Margaret T. Shannon, RN, PhD. Nurses Drug
Guide 2000. Stamford, CT: Appleton and Lange, 1999.
PERIODICALS

Campbell, D. C. ‘‘Parenteral Opioids for Labor Analgesia.’’
Clinical Obstetrics and Gynecology 46 (September
2003): 616–622.
Compton, P., and P. Athanasos. ‘‘Chronic Pain, Substance
Abuse and Addiction.’’ Nursing Clinics of North
America 38 (September 2003): 525–537.
Faragon, J. J., and P. J. Piliero. ‘‘Drug Interactions
Associated with HAART: Focus on Treatments for
Addiction and Recreational Drugs.’’ AIDS Reader 13
(September 2003): 433–450.
Markowitz, J. S., J. L. Donovan, C. L. DeVane, et al. ‘‘Effect
of St John’s Wort on Drug Metabolism by Induction of
Cytochrome P450 3A4 Enzyme.’’ Journal of the
American Medical Association 290 (September 17,
2003): 1500–1504.
Soares, L. G., M. Marins, and R. Uchoa. ‘‘Intravenous
Fentanyl for Cancer Pain: A ‘Fast Titration’ Protocol
for the Emergency Room.’’ Journal of Pain and
Symptom Management 26 (September 2003): 876–881.
Watson, C. P., D. Moulin, J. Watt-Watson, et al.
‘‘Controlled-Release Oxycodone Relieves Neuropathic
Pain: A Randomized Controlled Trial in Painful
Diabetic Neuropathy.’’ Pain 105 (September 2003):
71–78.
ORGANIZATIONS

National Center for Complementary and Alternative
Medicine (NCCAM) Clearinghouse. P.O. Box 7923,
Gaithersburg, MD 20898-7923. (888) 644-6226.
<http://nccam.nih.gov>.
U. S. Food and Drug Administration (FDA). 5600 Fishers
Lane, Rockville, MD 20857. (888) 463-6332. <http://
www.fda.gov>.

Nancy Ross-Flanigan
Rebecca J. Frey, PhD

Anaphylactic shock see Anaphylaxis
Anaphylactoid purpura see Allergic purpura

I Anaphylaxis
Definition
Anaphylaxis is a rapidly progressing, life-threatening allergic reaction.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Anaphylaxis is a type of allergic reaction, in which
the immune system responds to otherwise harmless
substances from the environment. Unlike other allergic reactions, however, anaphylaxis can kill. Reaction
may begin within minutes or even seconds of exposure,
and rapidly progress to cause airway constriction, skin
and intestinal irritation, and altered heart rhythms. In
severe cases, it can result in complete airway obstruction, shock, and death.

ACTH—Adrenocorticotropic hormone, a hormone
normally produced by the pituitary gland, sometimes taken as a treatment for arthritis and other
disorders.
Antibody—An immune system protein which
binds to a substance from the environment.
NSAIDs—Non-steroidal antiinflammatory drugs,
including aspirin and ibuprofen.
Tracheostomy tube—A tube which is inserted into
an incision in the trachea (tracheostomy) to relieve
upper airway obstruction.

Causes and symptoms
Causes
Like the majority of other allergic reactions, anaphylaxis is caused by the release of histamine and
other chemicals from mast cells. Mast cells are a type
of white blood cell and they are found in large numbers in the tissues that regulate exchange with the
environment: the airways, digestive system, and skin.
On their surfaces, mast cells display antibodies
called IgE (immunoglobulin type E). These antibodies
are designed to detect environmental substances to
which the immune system is sensitive. Substances
from a genuinely threatening source, such as bacteria
or viruses, are called antigens. A substance that most
people tolerate well, but to which others have an allergic response, is called an allergen. When IgE antibodies bind with allergens, they cause the mast cell to
release histamine and other chemicals, which spill out
onto neighboring cells.
The interaction of these chemicals with receptors
on the surface of blood vessels causes the vessels to
leak fluid into surrounding tissues, causing fluid accumulation, redness, and swelling. On the smooth muscle cells of the airways and digestive system, they cause
constriction. On nerve endings, they increase sensitivity and cause itching.
In anaphylaxis, the dramatic response is due both
to extreme hypersensivity to the allergen and its usually
systemic distribution. Allergens are more likely to cause
anaphylaxis if they are introduced directly into the
circulatory system by injection. However, exposure by
ingestion, inhalation, or skin contact can also cause
anaphylaxis. In some cases, anaphylaxis may develop
over time from less severe allergies.
Anaphylaxis is most often due to allergens in foods,
drugs, and insect venom. Specific causes include:


Fish, shellfish, and mollusks



Nuts and seeds

GALE ENCYCLOPEDIA OF MEDICINE



Stings of bees, wasps, or hornets



Papain from meat tenderizers



Vaccines, including flu and measles vaccines



Penicillin



Cephalosporins



Streptomycin



Gamma globulin



Insulin



Hormones (ACTH, thyroid-stimulating hormone)



Aspirin and other NSAIDs



Latex, from exam gloves or condoms, for example.

Exposure to cold or exercise can trigger anaphylaxis in some individuals.
Symptoms
Symptoms may include:


Urticaria (hives)



Swelling and irritation of the tongue or mouth



Swelling of the sinuses



Difficulty breathing



Wheezing



Cramping, vomiting, or diarrhea



Anxiety or confusion



Strong, very rapid heartbeat (palpitations)



Loss of consciousness.
Not all symptoms may be present.
191

Anaphylaxis

Description

Anemias

Diagnosis
Anaphylaxis is diagnosed based on the rapid
development of symptoms in response to a suspect
allergen. Identification of the culprit may be done
with RAST testing, a blood test that identifies IgE
reactions to specific allergens. Skin testing may be
done for less severe anaphylactic reactions.

I Anemias
Definition
Anemia is a condition characterized by abnormally low levels of healthy red blood cells or hemoglobin (the component of red blood cells that delivers
oxygen to tissues throughout the body).

Treatment

Description

Emergency treatment of anaphylaxis involves
injection of adrenaline (epinephrine) which constricts
blood vessels and counteracts the effects of histamine. Oxygen may be given, as well as intravenous
replacement fluids. Antihistamines may be used for
skin rash, and aminophylline for bronchial constriction. If the upper airway is obstructed, placement
of a breathing tube or tracheostomy tube may be
needed.

The tissues of the human body need a regular
supply of oxygen to stay healthy. Red blood cells,
which contain hemoglobin that allows them to deliver
oxygen throughout the body, live for only about 120
days. When they die, the iron they contain is returned
to the bone marrow and used to create new red blood
cells. Anemia develops when heavy bleeding causes
significant iron loss or when something happens to
slow down the production of red blood cells or to
increase the rate at which they are destroyed.

Prognosis

Types of anemia

The rapidity of symptom development is an indication of the likely severity of reaction: the faster
symptoms develop, the more severe the ultimate
reaction. Prompt emergency medical attention and
close monitoring reduces the likelihood of death.
Nonetheless, death is possible from severe anaphylaxis. For most people who receive rapid treatment,
recovery is complete.

Prevention
Avoidance of the allergic trigger is the only
reliable method of preventing anaphylaxis. For
insect allergies, this requires recognizing likely
nest sites. Preventing food allergies requires knowledge of the prepared foods or dishes in which the
allergen is likely to occur, and careful questioning
about ingredients when dining out. Use of a MedicAlert tag detailing drug allergies is vital to prevent
inadvertent administration during a medical
emergency.

Anemia can be mild, moderate, or severe enough
to lead to life-threatening complications. More than
400 different types of anemia have been identified.
Many of them are rare.
IRON DEFICIENCY ANEMIA. The onset of iron deficiency anemia is gradual and, at first, there may not be
any symptoms. The deficiency begins when the body
loses more iron than it derives from food and other
sources. Because depleted iron stores cannot meet the
red blood cell’s needs, fewer red blood cells develop. In
this early stage of anemia, the red blood cells look
normal, but they are reduced in number. Then the
body tries to compensate for the iron deficiency by
producing more red blood cells, which are characteristically small in size. Symptoms develop at this stage.
FOLIC ACID DEFICIENCY ANEMIA. Folic acid anemia is especially common in infants and teenagers.
Although this condition usually results from a dietary
deficiency, it is sometimes due to inability to absorb
enough folic acid from such foods as:


cheese



eggs



fish

Resources



green vegetables

OTHER



meat

The Meck Page. February 20, 1998. <http://
www.merck.com>.



milk



mushrooms



yeast

People prone to anaphylaxis should carry an
‘‘Epi-pen’’ or ‘‘Ana-kit,’’ which contain an adrenaline
dose ready for injection.

Richard Robinson
192

GALE ENCYCLOPEDIA OF MEDICINE

Aplastic—Exhibiting
incomplete
or
faulty
development.
Hemoglobin—An iron-containing pigment of red
blood cells composed of four amino acid chains
(alpha, beta, gamma, delta) that delivers oxygen
from the lungs to the tissues of the body.
Megaloblast—A large erythroblast (a red marrow
cell that synthesizes hemoglobin).

secreted by the stomach lining that combines with
B12 to help its absorption in the small intestine.
An illustration of normal red blood cells (left) and those in
three different types of anemia (from left), iron-deficiency
anemia, megaloblastic anemia, and sickle cell anemia.
(Illustration by John Bavosi, Custom Medical Stock Photo.
Reproduced by permission.)

Smoking raises the risk of developing this condition by interfering with the absorption of Vitamin C,
which the body needs to absorb folic acid. Folic acid
anemia can be a complication of pregnancy, when a
woman’s body needs eight times more folic acid than it
does otherwise.
VITAMIN B12 DEFICIENCY ANEMIA. Less common in
this country than folic acid anemia, vitamin B12 deficiency anemia is another type of megaloblastic anemia
that develops when the body doesn’t absorb enough of
this nutrient. Necessary for the creation of red blood
cells, B12 is found in meat and vegetables.

Large amounts of B12 are stored in the body, so this
condition may not become apparent until as much as
four years after B12 absorption stops or slows down. The
resulting drop in red blood cell production can cause:

Pernicious anemia usually strikes between the ages
of 50–60. Eating disorders or an unbalanced diet
increase the risk of developing pernicious anemia. So do:


diabetes mellitus



gastritis, stomach cancer, or stomach surgery



thyroid disease



family history of pernicious anemia

VITAMIN C DEFICIENCY ANEMIA. A rare disorder
that causes the bone marrow to manufacture abnormally small red blood cells, Vitamin C deficiency anemia
results from a severe, long-standing dietary deficiency.
HEMOLYTIC ANEMIA. Some people are born with
hemolytic anemia. Some acquire this condition, in
which infection or antibodies destroy red blood cells
more rapidly than bone marrow can replace them.

Hemolytic anemia can enlarge the spleen, accelerating the destruction of red blood cells (hemolysis).
Other complications of hemolytic anemia include:


pain



shock
gallstones and other serious health problems



loss of muscle control





loss of sensation in the legs, hands, and feet



soreness or burning of the tongue



weight loss



yellow-blue color blindness

THALASSEMIAS. An inherited form of hemolytic
anemia, thalassemia stems from the body’s inability
to manufacture as much normal hemoglobin as it
needs. There are two categories of thalassemia,
depending on which of the amino acid chains is
affected. (Hemoglobin is composed of four chains of
amino acids.) In alpha-thalassemia, there is an imbalance in the production of the alpha chain of amino
acids; in beta-thalassemia, there is an imbalance in the
beta chain. Alpha-thalassemias most commonly affect
blacks (25% have at least one gene); beta-thalassemias
most commonly affect people of Mediterranean ancestry and Southeast Asians.

The most common form of B12 deficiency is pernicious anemia. Since most people who eat meat or eggs
get enough B12 in their diets, a deficiency of this vitamin usually means that the body is not absorbing it
properly. This can occur among people who have had
intestinal surgery or among those who do not produce
adequate amounts of intrinsic factor, a chemical
GALE ENCYCLOPEDIA OF MEDICINE

193

Anemias

KEY TERMS

Anemias

Characterized by production of red blood cells
that are unusually small and fragile, thalassemia only
affects people who inherit the gene for it from each
parent (autosomal recessive inheritance).



recent severe illness



long-term exposure to industrial chemicals



use of anticancer drugs and certain other medications

AUTOIMMUNE HEMOLYTIC ANEMIAS. Warm antibody hemolytic anemia is the most common type of
this disorder. This condition occurs when the body
produces autoantibodies that coat red blood cells.
The coated cells are destroyed by the spleen, liver, or
bone marrow.

ANEMIA OF CHRONIC DISEASE. Cancer, chronic
infection or inflammation, and kidney and liver disease often cause mild or moderate anemia. Chronic
liver failure generally produces the most severe symptoms. People infected with the Human immunodeficiency virus (HIV) that causes AIDS often face severe
fatigue.

Warm antibody hemolytic anemia is more common in women than in men. About one-third of
patients who have warm antibody hemolytic anemia
also have lymphoma, leukemia, lupus, or connective
tissue disease.
In cold antibody hemolytic anemia, the body
attacks red blood cells at or below normal body temperature. The acute form of this condition frequently
develops in people who have had pneumonia, mononeucleosis, or other acute infections. It tends to be
mild and short-lived, and disappears without
treatment.
Chronic cold antibody hemolytic anemia is most
common in women and most often affects those who
are over 40 and who have arthritis. This condition
usually lasts for a lifetime, generally causing few symptoms. However, exposure to cold temperatures can
accelerate red blood cell destruction, causing fatigue,
joint aches, and discoloration of the arms and hands.
SICKLE CELL ANEMIA. Sickle cell anemia is a

chronic, incurable condition that causes the body to
produce defective hemoglobin, which forces red blood
cells to assume an abnormal crescent shape. Unlike
normal oval cells, fragile sickle cells can’t hold enough
hemoglobin to nourish body tissues. The deformed
shape makes it hard for sickle cells to pass through
narrow blood vessels. When capillaries become
obstructed, a life-threatening condition called sickle
cell crisis is likely to occur.
Sickle cell anemia is hereditary. It almost always
affects blacks and people of Mediterranean descent. A
child who inherits the sickle cell gene from each parent
will have the disease. A child who inherits the sickle
cell gene from only one parent carries the sickle cell
trait, but does not have the disease.
APLASTIC ANEMIA. Sometimes curable by bone
marrow transplant, but potentially fatal, aplastic anemia is characterized by decreased production of red
and white blood cells and platelets (disc-shaped cells
that allow the blood to clot). This disorder may be
inherited or acquired as a result of:

194

Causes and symptoms
Anemia is caused by bleeding, decreased red
blood cell production, or increased red blood cell
destruction. Poor diet can contribute to vitamin deficiency and iron deficiency anemias in which fewer red
blood cells are produced. Hereditary disorders and
certain diseases can cause increased blood cell destruction. However, excessive bleeding is the most common
cause of anemia, and the speed with which blood loss
occurs has a significant effect on the severity of symptoms. Chronic blood loss is usually a consequence of:


cancer



gastrointestinal tumors



diverticulosis



polyposis



heavy menstrual flow



hemorrhoids



nosebleeds



stomach ulcers



long-standing alcohol abuse
Acute blood loss is usually the result of:



childbirth



injury



a ruptured blood vessel



surgery

When a lot of blood is lost within a short time,
blood pressure and the amount of oxygen in the body
drop suddenly. Heart failure and death can follow.
Loss of even one-third of the body’s blood volume
in the space of several hours can be fatal. More gradual blood loss is less serious, because the body has
time to create new red blood cells to replace those that
have been lost.
GALE ENCYCLOPEDIA OF MEDICINE

Weakness, fatigue, and a run-down feeling may be
signs of mild anemia. Skin that is pasty or sallow, or
lack of color in the creases of the palm, gums, nail
beds, or lining of the eyelids are other signs of anemia.
Someone who is weak, tires easily, is often out of
breath, and feels faint or dizzy may be severely anemic.
Other symptoms of anemia are:


angina pectoris (chest pain, often accompanied by a
choking sensation that provokes severe anxiety)



cravings for ice, paint, or dirt



headache



inability to concentrate, memory loss



inflammation of the mouth (stomatitis) or tongue
(glossitis)



insomnia



irregular heartbeat



loss of appetite



nails that are dry, brittle, or ridged



rapid breathing



sores in the mouth, throat, or rectum



sweating



swelling of the hands and feet



thirst



tinnitus (ringing in the ears)



unexplained bleeding or bruising

In pernicious anemia, the tongue feels unusually
slick. A patient with pernicious anemia may have:


problems with movement or balance



tingling in the hands and feet



confusion, depression, and memory loss

Pernicious anemia can damage the spinal cord. A
doctor should be notified whenever symptoms of this
condition occur.
A doctor should also be notified if a patient who
has been taking iron supplements develops:


diarrhea



cramps



vomiting

Diagnosis
Personal and family health history may suggest
the presence of certain types of anemia. Laboratory
tests that measure the percentage of red blood cells or
GALE ENCYCLOPEDIA OF MEDICINE

the amount of hemoglobin in the blood are used to
confirm diagnosis and determine which type of anemia
is responsible for a patient’s symptoms. X rays and
examinations of bone marrow may be used to identify
the source of bleeding.

Treatment
Anemia due to nutritional deficiencies can usually
be treated at home with iron supplements or self administered injections of vitamin B12. People with folic
acid anemia should take oral folic acid replacements.
Vitamin C deficiency anemia can be cured by taking
one vitamin C tablet a day.
Surgery may be necessary to treat anemia caused
by excessive loss of blood. Transfusions of red blood
cells may be used to accelerate production of red blood
cells.
Medication or surgery may also be necessary to
control heavy menstrual flow, repair a bleeding ulcer,
or remove polyps (growths or nodules) from the
bowels.
Patients with thalassemia usually do not require
treatment. However people with a severe form may
require periodic hospitalization for blood transfusions
and/or bone marrow transplantation.
SICKLE CELL ANEMIA. Treatment for sickle cell
anemia involves regular eye examinations, immunizations for pneumonia and infectious diseases, and
prompt treatment for sickle cell crises and infections
of any kind. Psychotherapy or counseling may help
patients deal with the emotional impact of this
condition.
VITAMIN B12 DEFICIENCY ANEMIA. A life-long regimen of B12 shots is necessary to control symptoms of
pernicious anemia. The patient may be advised to limit
physical activity until treatment restores strength and
balance.
APLASTIC ANEMIA. People who have aplastic anemia are especially susceptible to infection. Treatment
for aplastic anemia may involve blood transfusions
and bone marrow transplant to replace malfunctioning cells with healthy ones.
ANEMIA OF CHRONIC DISEASE. There is no specific
treatment for anemia associated with chronic disease,
but treating the underlying illness may alleviate this
condition. Erythropoietin is a hormone that stimulates production of red blood cells. It is sometimes
used to treat anemia from kidney disease or cancer
chemotherapy. This type of anemia rarely becomes
severe. If it does, transfusions or hormone treatments

195

Anemias

Symptoms

Anemias

to stimulate red blood cell production may be prescribed. A working group met in 2004 to address the
specific management of anemia in patients infected
with HIV.
HEMOLYTIC ANEMIA. There is no specific treatment for cold-antibody hemolytic anemia. About
one-third of patients with warm-antibody hemolytic
anemia respond well to large doses of intravenous and
oral corticosteroids, which are gradually discontinued
as the patient’s condition improves. Patients with this
condition who don’t respond to medical therapy must
have the spleen surgically removed. This operation
controls anemia in about one-half of the patients on
whom it’s performed. Immune-system suppressants
are prescribed for patients whose surgery is not
successful.

Self-care
Anyone who has anemia caused by poor nutrition
should modify his or her diet to include more vitamins,
minerals, and iron. Vitamin C can stimulate iron
absorption. The following foods are also good sources
of iron:

on a deep healing level with crisis intervention when
necessary.
Many alternative therapies for iron-deficiency
anemia focus on adding iron-rich foods to the
diet or on techniques to improve circulation and
digestion. Iron supplementation, especially with
iron citrate (less likely to cause constipation), is
used by alternative practitioners. This can be given
in combination with herbs that are rich in iron.
Some examples of iron-rich herbs are dandelion
(Taraxacum officinale), parsley (Petroselinum
crispum), and nettle (Urtica dioica). The homeopathic remedy ferrum phosphoricum can also be
helpful.
An iron-rich herbal tonic can also me made using
the following recipe:


soak 1/2 oz of yellow dock root and 1/2 oz dandelion
root in 1 qt of boiled water for four to 8 hours



strain and simmer until the amount of liquid is
reduced to 1 cup



remove from heat and add 1/2 cup black strap
molasses, mixing well
store in refrigerator; take 1 tsp-2 Tbsp daily



almonds





broccoli



dried beans



dried fruits



enriched breads and cereals



lean red meat



liver



potatoes

Other herbal remedies used to treat irondeficiency anemia aim to improve the digestion.
Gentian (Gentiana lutea) is widely used in Europe to
treat anemia and other nutritionally based disorders.
The bitter qualities of gentian help stimulate the digestive system, making iron and other nutrients more
available for absorption. This bitter herb can be
brewed into tea or purchased as an alcoholic extract
(tincture).



poultry



rice

Other herbs recommended to promote digestion
include:



shellfish



anise (Pimpinella anisum)



tomatoes



caraway (Carum carvi)



cumin (Cuminum cyminum)



linden (Tilia spp.)



licorice (Glycyrrhiza glabra)

Because light and heat destroy folic acid, fruits
and vegetables should be eaten raw or cooked as little
as possible.

Alternative treatment
As is the case in standard medical treatment, the
cause of the specific anemia will determine the alternative treatment recommended. If the cause is a deficiency, for example iron deficiency, folic acid
deficiency, B12 deficiency, or vitamin C deficiency,
supplementation is the treatment. For extensive
blood loss, the cause should be identified and corrected. Other types of anemias should be addressed
196

Traditional Chinese treatments for anemia
include:


acupuncture to stimulate a weakened spleen



asian ginseng (Panax ginseng) to restore energy



dong quai (Angelica sinensis) to control heavy menstrual bleeding



a mixture of dong quai and Chinese foxglove
(Rehmannia glutinosa) to clear a sallow complexion
GALE ENCYCLOPEDIA OF MEDICINE



not taking medication that has triggered hemolytic
anemia and not eating foods that have caused hemolysis (breakdown of red blood cells)



receiving regular B12 shots to prevent pernicious
anemia resulting from gastritis or stomach surgery

Folic-acid and iron-deficiency anemias
It usually takes three to six weeks to correct folic
acid or iron deficiency anemia. Patients should continue taking supplements for another six months to
replenish iron reserves. They should have periodic
blood tests to make sure the bleeding has stopped
and the anemia has not recurred.
Pernicious anemia
Although pernicious anemia is considered incurable, regular B12 shots will alleviate symptoms and
reverse complications. Some symptoms will disappear
almost as soon as treatment begins.

Resources
PERIODICALS

‘‘Biopharmaceuitcal Company Announces Manufacturing
Agreement for Anemia Drug.’’ Obesity, Wellness, &
Fitness Week (September 4, 2004): 406.
‘‘Management Strategy for Anemia in HIV Infection
Elucidated.’’ Immunotherapy Weekly (July 7, 2004): 75.

Maureen Haggerty
Teresa G. Odle

Aplastic anemia
Aplastic anemia can sometimes be cured by bone
marrow transplantation. If the condition is due to
immunosuppressive drugs, symptoms may disappear
after the drugs are discontinued.

Anencephaly see Congenital brain defects

I Anesthesia, general

Sickle cell anemia
Although sickle cell anemia cannot be cured,
effective treatments enable patients with this disease
to enjoy longer, more productive lives.
Thalassemia
People with mild thalassemia (alpha thalassemia
trait or beta thalassemia minor) lead normal lives and
do not require treatment. Those with severe thalassemia
may require bone marrow transplantation. Genetic therapy is is being investigated and may soon be available.
Hemolytic anemia
Acquired hemolytic anemia can generally be
cured when the cause is removed.

Definition
General anesthesia is the induction of a state of
unconsciousness with the absence of pain sensation
over the entire body, through the administration of
anesthetic drugs. It is used during certain medical and
surgical procedures.

Purpose
General anesthesia has many purposes including:


pain relief (analgesia)



blocking memory of the procedure (amnesia)



producing unconsciousness



inhibiting normal body reflexes to make surgery safe
and easier to perform



relaxing the muscles of the body

Prevention
Inherited anemias cannot be prevented. Genetic
counseling can help parents cope with questions and
concerns about transmitting disease-causing genes to
their children.
Avoiding excessive use of alcohol, eating a balanced
diet that contains plenty of iron-rich foods, and taking
a daily multivitamin can help prevent anemia.

Description
Anesthesia performed with general anesthetics
occurs in four stages which may or may not be observable because they can occur very rapidly:


Stage One: Analgesia. The patient experiences
analgesia or a loss of pain sensation but remains
conscious and can carry on a conversation.



Stage Two: Excitement. The patient may experience
delirium or become violent. Blood pressure rises and

Methods of preventing specific types of anemia
include:


avoiding lengthy exposure to industrial chemicals
and drugs known to cause aplastic anemia

GALE ENCYCLOPEDIA OF MEDICINE

197

Anesthesia, general

Prognosis

Anesthesia, general

KEY TERMS

ANESTHETICS: HOW THEY WORK

Type

Name(s)

Administered

Affect

General

Halothane,
Enflurane
Isoflurane,
Ketamine,
Nitrous Oxide,
Thiopental
Mepivacaine,
Chloroprocaine,
Lidocaine

Intravenously,
Inhalation

Produces total
unconsciousness
affecting the entire
body

Regional

Local

Topical

Procaine,
Lidocaine,
Tetracaine,
Bupivacaine

Benzocaine,
Lidocaine
Dibucaine,
Pramoxine,
Butamben,
Tetracaine

Intravenously

Intravenously

Demal
(Sprays,
Drope,
Ointments,
Creams, Gels)

Temporarily interrupts transmission
of nerve impulses
(temperature,
touch, pain) and
motor functions in
a large area to be
treated; does not
produce
unconsciousness
Temporarily blocks
transmission of
nerve impulses and
motor functions in
a specific area;
does not produce
unconsciousness
Temporarily blocks
nerve endings in
skin and mucous
membranes; does
not produce
unconsciousness

becomes irregular, and breathing rate increases.
This stage is typically bypassed by administering a
barbiturate, such as sodium pentothal, before the
anesthesia.




Stage Three: Surgical Anesthesia. During this stage,
the skeletal muscles relax, and the patient’s breathing
becomes regular. Eye movements slow, then stop,
and surgery can begin.
Stage Four: Medullary Paralysis. This stage occurs if
the respiratory centers in the medulla oblongata of
the brain that control breathing and other vital functions cease to function. Death can result if the patient
cannot be revived quickly. This stage should never be
reached. Careful control of the amounts of anesthetics administered prevent this occurrence.

Agents used for general anesthesia may be either
gases or volatile liquids that are vaporized and inhaled
with oxygen, or drugs delivered intravenously. A combination of inhaled anesthetic gases and intravenous
drugs are usually delivered during general anesthesia;
this practice is called balanced anesthesia and is used
because it takes advantage of the beneficial effects of
each anesthetic agent to reach surgical anesthesia. If
necessary, the extent of the anesthesia produced by
198

Amnesia—The loss of memory.
Analgesia—A state of insensitivity to pain even
though the person remains fully conscious.
Anesthesiologist—A medical specialist who administers an anesthetic to a patient before he is treated.
Anesthetic—A drug that causes unconsciousness
or a loss of general sensation.
Arrhythmia —Abnormal heart beat.
Barbiturate—A drug with hypnotic and sedative
effects.
Catatonia—Psychomotor disturbance characterized by muscular rigidity, excitement or stupor.
Hypnotic agent—A drug capable of inducing a
hypnotic state.
Hypnotic state—A state of heightened awareness
that can be used to modulate the perception of pain.
Hypoxia—Reduction of oxygen supply to the tissues.
Malignant hyperthermia—A type of reaction
(probably with a genetic origin) that can occur
during general anesthesia and in which the patient
experiences a high fever, muscle rigidity, and irregular heart rate and blood pressure.
Medulla oblongata—The lowest section of the
brainstem, located next to the spinal cord. The
medulla is the site of important cardiac and respiratory regulatory centers.
Opioid—Any morphine-like synthetic narcotic that
produces the same effects as drugs derived from the
opium poppy (opiates), such as pain relief, sedation, constipation and respiratory depression.
Pneumothorax—A collapse of the lung.
Stenosis—A narrowing or constriction of the diameter of a passage or orifice, such as a blood vessel.

inhaling a general anesthetic can be rapidly modified
by adjusting the concentration of the anesthetic in the
oxygen that is breathed by the patient. The degree of
anesthesia produced by an intravenously injected
anesthesic is fixed and cannot be changed as rapidly.
Most commonly, intravenous anesthetic agents are
used for induction of anesthesia and then followed
by inhaled anesthetic agents.
General anesthesia works by altering the flow of
sodium molecules into nerve cells (neurons) through
the cell membrane. Exactly how the anesthetic does
this is not understood since the drug apparently does
GALE ENCYCLOPEDIA OF MEDICINE

When general anesthesia was first introduced in
medical practice, ether and chloroform were inhaled
with the physician manually covering the patient’s
mouth. Since then, general anesthesia has become much
more sophisticated. During most surgical procedures,
anesthetic agents are now delivered and controlled by
computerized equipment that includes anesthetic gas
monitoring as well as patient monitoring equipment.
Anesthesiologists are the physicians that specialize in
the delivery of anesthetic agents. Currently used inhaled
general anesthetics include halothane, enflurane, isoflurane, desfluorane, sevofluorane, and nitrous oxide.








Halothane (Fluothane) is a powerful anesthetic and
can easily be overadministered. This drug causes
unconsciousness but little pain relief so it is often
used with other agents to control pain. Very rarely,
it can be toxic to the liver in adults, causing death. It
also has the potential for causing serious cardiac
dysrhythmias. Halothane has a pleasant odor, and
was frequently the anesthetic of choice for use with
children, but since the introduction of sevofluorane
in the 1990s, halothane use has declined.
Enflurane (Ethrane) is less potent and results in a
more rapid onset of anesthesia and faster awakening
than halothane. In addition, it acts as an enhancer of
paralyzing agents. Enflurane has been found to
increase intracranial pressure and the risk of seizures;
therefore, its use is contraindicated in patients with
seizure disorders.
Isoflurane (Forane) is not toxic to the liver but can
cause some cardiac irregularities. Isofluorane is often
used in combination with intravenous anesthetics for
anesthesia induction. Awakening from anesthesia is
faster than it is with halothane and enfluorane.
Desfluorane (Suprane) may increase the heart rate
and should not be used in patients with aortic valve
stenosis; however, it does not usually cause heart
arrhythmias. Desflurane may cause coughing and excitation during induction and is therefore used with
intravenous anesthetics for induction. Desflurane is

GALE ENCYCLOPEDIA OF MEDICINE

rapidly eliminated and awakening is therefore faster
than with other inhaled agents.


Sevofluorane (Ultane) may also cause increased
heart rate and should not be used in patients with
narrowed aortic valve (stenosis); however, it does
not usually cause heart arrhythmias. Unlike desfluorane, sevofluorane does not cause any coughing
or other related side effects, and can therefore be
used without intravenous agents for rapid induction. For this reason, sevofluorane is replacing
halothane for induction in pediatric patients. Like
desfluorane, this agent is rapidly eliminated and
allows rapid awakening.



Nitrous oxide (laughing gas) is a weak anesthetic and
is used with other agents, such as thiopental, to
produce surgical anesthesia. It has the fastest induction and recovery and is the safest because it does not
slow breathing or blood flow to the brain. However,
it diffuses rapidly into air-containing cavities and can
result in a collapsed lung (pneumothorax) or lower
the oxygen contents of tissues (hypoxia).

Commonly administered intravenous anesthetic
agents include ketamine, thiopental, opioids, and
propofol.


Ketamine (Ketalar) affects the senses, and produces
a dissociative anesthesia (catatonia, amnesia, analgesia) in which the patient may appear awake and
reactive, but cannot respond to sensory stimuli.
These properties make it especially useful for use in
developing countries and during warfare medical
treatment. Ketamine is frequently used in pediatric
patients because anesthesia and analgesia can be
achieved with an intramuscular injection. It is also
used in high-risk geriatric patients and in shock cases,
because it also provides cardiac stimulation.



Thiopental (Pentothal) is a barbiturate that induces
a rapid hypnotic state of short duration. Because
thiopental is slowly metabolized by the liver, toxic
accumulation can occur; therefore, it should not be
continuously infused. Side effects include nausea and
vomiting upon awakening.



Opioids include fentanyl, sufentanil, and alfentanil,
and are frequently used prior to anesthesia and surgery as a sedative and analgesic, as well as a continuous infusion for primary anesthesia. Because opioids
rarely affect the cardiovascular system, they are particularly useful for cardiac surgery and other highrisk cases. Opioids act directly on spinal cord receptors, and are freqently used in epidurals for spinal
anesthesia. Side effects may include nausea and
vomiting, itching, and respiratory depression.
199

Anesthesia, general

not bind to any receptor on the cell surface and does
not seem to affect the release of chemicals that transmit nerve impulses (neurotransmitters) from the nerve
cells. It is known, however, that when the sodium
molecules do not get into the neurons, nerve impulses
are not generated and the brain becomes unconscious,
does not store memories, does not register pain
impulses from other areas of the body, and does not
control involuntary reflexes. Although anesthesia may
feel like deep sleep, it is not the same. In sleep, some parts
of the brain speed up while others slow down. Under
anesthesia, the loss of consciousness is more widespread.

Anesthesia, general



Propofol (Diprivan) is a nonbarbiturate hypnotic
agent and the most recently developed intravenous
anesthetic. Its rapid induction and short duration of
action are identical to thiopental, but recovery
occurs more quickly and with much less nausea and
vomiting. Also, propofol is rapidly metabolized in
the liver and excreted in the urine, so it can be used
for long durations of anesthesia, unlike thiopental.
Hence, propofol is rapidly replacing thiopental as an
intravenous induction agent. It is used for general
surgery, cardiac surgery, neurosurgery, and pediatric
surgery.

General anesthetics are given only by anesthesiologists, the medical professionals trained to use them.
These specialists consider many factors, including a
patient’s age, weight, medication allergies, medical
history, and general health, when deciding which anesthetic or combination of anesthetics to use. General
anesthetics are usually inhaled through a mask or a
breathing tube or injected into a vein, but are also
sometimes given rectally.
General anesthesia is much safer today than it was in
the past. This progress is due to faster-acting anesthetics,
improved safety standards in the equipment used to
deliver the drugs, and better devices to monitor breathing, heart rate, blood pressure, and brain activity during
surgery. Unpleasant side effects are also less common.

Recommended dosage
The dosage depends on the type of anesthetic, the
patient’s age and physical condition, the type of surgery
or medical procedure being done, and other medication
the patient takes before, during, or after surgery.

Precautions
Although the risks of serious complications from
general anesthesia are very low, they can include heart
attack, stroke, brain damage, and death. Anyone
scheduled to undergo general anesthesia should thoroughly discuss the benefits and risks with a physician.
The risks of complications depend, in part, on a
patient’s age, sex, weight, allergies, general health,
and history of smoking, drinking alcohol, or drug
use. Some of these risks can be minimized by ensuring
that the physician and anesthesiologist are fully
informed of the detailed health condition of the
patient, including any drugs that he or she may be
using. Older people are especially sensitive to the
effects of certain anesthetics and may be more likely
to experience side effects from these drugs.
Patients who have had general anesthesia should
not drink alcoholic beverages or take medication that
200

slow down the central nervous system (such as antihistamines, sedatives, tranquilizers, sleep aids, certain pain
relievers, muscle relaxants, and anti-seizure medication) for at least 24 hours, except under a doctor’s care.
Special conditions
People with certain medical conditions are at greater
risk of developing problems with anesthetics. Before
undergoing general anesthesia, anyone with the following conditions should absolutely inform their doctor.
ALLERGIES. Anyone who has had allergic or other
unusual reactions to barbiturates or general anesthetics
in the past should notify the doctor before having general anesthesia. In particular, people who have had
malignant hyperthermia or whose family members
have had malignant hyperthermia during or after
being given an anesthetic should inform the physician.
Signs of malignant hyperthermia include rapid, irregular heartbeat, breathing problems, very high fever, and
muscle tightness or spasms. These symptoms can occur
following the administration of general anesthesia
using inhaled agents, especially halothane. In addition,
the doctor should also be told about any allergies to
foods, dyes, preservatives, or other substances.
PREGNANCY. The effects of anesthetics on pregnant women and fetuses vary, depending on the type
of drug. In general, giving large amounts of general
anesthetics to the mother during labor and delivery
may make the baby sluggish after delivery. Pregnant
women should discuss the use of anesthetics during
labor and delivery with their doctors. Pregnant women
who may be given general anesthesia for other medical
procedures should ensure that the treating physician is
informed about the pregnancy.
BREASTFEEDING. Some general anesthetics pass
into breast milk, but they have not been reported to
cause problems in nursing babies whose mothers were
given the drugs.
OTHER MEDICAL CONDITIONS. Before being given
a general anesthetic, a patient who has any of the
following conditions should inform his or her doctor:
 neurological conditions, such as epilepsy or stroke


problems with the stomach or esophagus, such as
ulcers or heartburn



eating disorders



loose teeth, dentures, bridgework



heart disease or family history of heart problems



lung diseases, such as emphysema or asthma



history of smoking



immune system diseases
GALE ENCYCLOPEDIA OF MEDICINE

arthritis or any other conditions that affect
movement



diseases of the endocrine system, such as diabetes or
thyroid problems

Side effects
Because general anesthetics affect the central nervous system, patients may feel drowsy, weak, or tired
for as long as a few days after having general anesthesia. Fuzzy thinking, blurred vision, and coordination
problems are also possible. For these reasons, anyone
who has had general anesthesia should not drive,
operate machinery, or perform other activities that
could endanger themselves or others for at least 24
hours, or longer if necessary.
Most side effects usually disappear as the anesthetic wears off. A nurse or doctor should be notified if
these or other side effects persist or cause problems,
such as:

Interactions
General anesthetics may interact with other medicines. When this happens, the effects of one or both of
the drugs may be altered or the risk of side effects may
be greater. Anyone scheduled to undergo general
anesthesia should inform the doctor about all other
medication that he or she is taking. This includes prescription drugs, nonprescription medicines, and street
drugs. Serious and possibly life-threatening reactions
may occur when general anesthetics are given to people who use street drugs, such as cocaine, marijuana,
phencyclidine (PCP or angel dust), amphetamines
(uppers), barbiturates (downers), heroin, or other narcotics. Anyone who uses these drugs should make sure
their doctor or dentist knows what they have taken.
Resources
BOOKS

Dobson, Michael B. Anaesthesia at the District Hospital.
2nd ed. World Health Organization, 2000.



Headache

PERIODICALS



vision problems, including blurred or double vision



shivering or trembling



muscle pain

Adachi, Y.U., K. Watanabe, H. Higuchi, and T. Satoh.
‘‘The Determinants of Propofol Induction of
Anesthesia Dose.’’ Anesthesia and Analgesia 92 (2001):
656-661.



dizziness, lightheadedness, or faintness



drowsiness



mood or mental changes



nausea or vomiting



sore throat



nightmares or unusual dreams

A doctor should be notified as soon as possible if
any of the following side effects occur within two
weeks of having general anesthesia:


severe headache



pain in the stomach or abdomen



back or leg pain



severe nausea



black or bloody vomit



unusual tiredness or weakness



weakness in the wrist and fingers



weight loss or loss of appetite



increase or decrease in amount of urine



pale skin



yellow eyes or skin

GALE ENCYCLOPEDIA OF MEDICINE

OTHER

Wenker, O. ‘‘Review of Currently Used Inhalation
Anesthetics Part I.’’ ‘‘The Internet Journal of
Anesthesiology.’’ 1999. <http://www.ispub.com/
journals/IJA/Vol3N2/inhal1.htm>.

Jennifer Sisk

I Anesthesia, local
Definition
Local or regional anesthesia involves the injection
or application of an anesthetic drug to a specific area
of the body, as opposed to the entire body and brain as
occurs during general anesthesia.

Purpose
Local anesthetics are used to prevent patients
from feeling pain during medical, surgical, or dental
procedures. Over-the-counter local anesthetics are
also available to provide temporary relief from pain,
irritation, and itching caused by various conditions,
201

Anesthesia, local



Anesthesia, local

KEY TERMS
Canker sore—A painful sore inside the mouth.
Cold sore—A small blister on the lips or face,
caused by a virus. Also called a fever blister.
Epidural space—The space surrounding the spinal
fluid sac.
Malignant hyperthermia—A type of reaction
(probably with a genetic basis) that can occur during general anesthesia in which the patient experiences a high fever, the muscles become rigid, and
the heart rate and blood pressure fluctuate.
Subarachnoid space—The space surrounding the
spinal cord that is filled with cerebrospinal fluid.

into four groups: injectable, topical, dental (noninjectable), and ophthalmic.
Local and regional anesthesia work by altering the
flow of sodium molecules into nerve cells or neurons
through the cell membrane. Exactly how the anesthetic does this is not understood, since the drug
apparently does not bind to any receptor on the cell
surface and does not seem to affect the release of
chemicals that transmit nerve impulses (neurotransmitters) from the nerve cells. It is known, however,
that when the sodium molecules do not get into the
neurons, nerve impulses are not generated and pain
impulses are not transmitted to the brain. The duration of action of an anesthetic depends on the type and
amount of anesthetic administered.

Topical—Not ingested; applied to the outside of
the body, for example to the skin, eye, or mouth.

Regional anesthesia
Types of regional anesthesia include:


Spinal anesthesia. Spinal anesthesia involves the
injection of a small amount of local anesthetic
directly into the cerebrospinal fluid surrounding the
spinal cord (the subarachnoid space). Blood pressure
drops are common but are easily treated.



Epidural anesthesia. Epidural anesthesia involves
the injection of a large volume of local anesthetic
directly into the space surrounding the spinal fluid
sac (the epidural space), not into the spinal fluid.
Pain relief occurs more slowly but is less likely to
produce blood pressure drops. Also, the block can be
maintained for long periods, even days.



Surgeries involving the chest and abdomen are
usually performed under general anesthesia.

Nerve blocks. Nerve blocks involve the injection of
an anesthetic into the area around a nerve that supplies a particular region of the body, preventing the
nerve from carrying nerve impulses to the brain.

Local and regional anesthesia have advantages
over general anesthesia in that patients can avoid
some unpleasant side effects, can receive longer lasting
pain relief, have reduced blood loss, and maintain a
sense of psychological comfort by not losing
consciousness.

Anesthetics may be administered with another
drug, such as epinephrine (adrenaline), which decreases
bleeding, and sodium bicarbonate to decrease the acidity of a drug so that it will work faster. In addition,
drugs may be administered to help a patient remain
calm and more comfortable or to make them sleepy.

such as cold sores, canker sores, sore throats, sunburn,
insect bites, poison ivy, and minor cuts and scratches.
Types of surgery or medical procedures that regularly make use of local or regional anesthesia include
the following:


biopsies in which skin or tissue samples are taken for
diagnostic procedures



childbirth



surgeries on the arms, hands, legs, or feet



eye surgery



surgeries involving the urinary tract or sexual organs

Description
Regional anesthesia typically affects a larger area
than local anesthesia, for example, everything below
the waist. As a result, regional anesthesia may be used
for more involved or complicated surgical or medical
procedures. Regional anesthetics are injected. Local
anesthesia involves the injection into the skin or muscle or application to the skin of an anesthetic directly
where pain will occur. Local anesthesia can be divided
202

Local anesthesia
INJECTABLE LOCAL ANESTHETICS. These medicines
are given by injection to numb and provide pain relief
to some part of the body during surgery, dental procedures, or other medical procedures. They are given
only by a trained health care professional and only in a
doctor’s office or a hospital. Some commonly used
injectable local anesthetics are procaine (Novocain),
lidocaine (Dalcaine, Dilocaine, L-Caine, Nervocaine,

GALE ENCYCLOPEDIA OF MEDICINE

other

brands),

and

tetracaine

told about any allergies to foods, dyes, preservatives,
or other substances.

TOPICAL ANESTHETICS. Topical anesthetics, such
as benzocaine, lidocaine, dibucaine, pramoxine,
butamben, and tetracaine, relieve pain and itching by
deadening the nerve endings in the skin. They are
ingredients in a variety of nonprescription products
that are applied to the skin to relieve the discomfort of
sunburn, insect bites or stings, poison ivy, and minor
cuts, scratches, and burns. These products are sold as
creams, ointments, sprays, lotions, and gels.

Older people may be more sensitive to the effects
of local anesthetics, especially lidocaine. This
increased sensitivity may increase the risk of side
effects. Older people who use nonprescription local
anesthetics should be especially careful not to use
more than the recommended amount. Children also
may be especially sensitive to the effects of some local
anesthetics, which may increase the chance of side
effects. Anyone using these medicines on a child
should be careful not to use more than the amount
that is recommended for children. Certain types of
local anesthetics should not be used at all young children. Follow package directions carefully and check
with a doctor of pharmacist if there are any questions.

DENTAL ANESTHETICS (NON-INJECTABLE). Some
local anesthetics are intended for pain relief in the
mouth or throat. They may be used to relieve throat
pain, teething pain, painful canker sores, toothaches,
or discomfort from dentures, braces, or bridgework.
Some dental anesthetics are available only with a doctor’s prescription. Others may be purchased without a
prescription, including products such as Num-Zit,
Orajel, Chloraseptic lozenges, and Xylocaine.
OPHTHALMIC ANESTHETICS. Other local anesthetics are designed for use in the eye. The ophthalmic
anesthetics proparacaine and tetracaine are used to
numb the eye before certain eye examinations. Eye
doctors may also use these medicines before measuring eye pressure or removing stitches or foreign objects
from the eye. These drugs are to be given only by a
trained health care professional.

Recommended dosage
The recommended dosage depends on the type of
local anesthetic and the purpose for which it is being
used. When using a nonprescription local anesthetic,
follow the directions on the package. Questions concerning how to use a product should be referred to a
medical doctor, dentist, or pharmacist.

Precautions
People who strongly feel that they cannot psychologically cope with being awake and alert during certain procedures may not be good candidates for local
or regional anesthesia. Other medications may be
given in conjunction with the anesthetic, however, to
relieve anxiety and help the patient relax.
Local anesthetics should be used only for the conditions for which they are intended. For example, a
topical anesthetic meant to relieve sunburn pain
should not be used on cold sores. Anyone who has
had an unusual reaction to any local anesthetic in the
past should check with a doctor before using any type
of local anesthetic again. The doctor should also be
GALE ENCYCLOPEDIA OF MEDICINE

Regional anesthetics
Serious, possibly life-threatening, side effects may
occur when anesthetics are given to people who use
street drugs. Anyone who uses cocaine, marijuana,
amphetamines, barbiturates, phencyclidine (PCP, or
angel dust), heroin, or other street drugs should
make sure their doctor or dentist knows what they
have used.
Patients who have had a particular kind of reaction called malignant hyperthermia (or who have one
or more family members who have had this problem)
during or just after receiving a general anesthetic
should inform their doctors before receiving any kind
of anesthetic. Signs of malignant hyperthermia include
fast and irregular heartbeat, very high fever, breathing
problems, and muscle spasms or tightness.
Although problems are rare, some unwanted side
effects may occur when regional anesthetics are used
during labor and delivery. These anesthetics can prolong labor and increase the risk of Cesarean section.
Pregnant women should discuss with their doctors the
risks and benefits of being given these drugs.
Patients should not drive or operate other
machinery immediately following a procedure involving regional anesthesia, due to numbness and weakness, or if local anesthesia also included drugs to make
the patient sleep or strong pain medications. Injection
sites should be kept clean, dry, and uncovered to prevent infection.
Injectable local anesthetics
Until the anesthetic wears off, patients should be
careful not to injure the numbed area. If the anesthetic
203

Anesthesia, local

Xylocaine, and
(Pontocaine).

Anesthesia, local

was used in the mouth, do not eat or chew gum until
feeling returns.
Topical anesthetics
Unless advised by a doctor, topical anesthetics
should not be used on or near any part of the body
with large sores, broken or scraped skin, severe injury,
or infection. They should also not be used on large
areas of skin. Some topical anesthetics contain alcohol
and should not be used near an open flame, or while
smoking.
Anyone using a topical anesthetic should be careful not to get this medication in the eyes, nose, or
mouth. When using a spray form of this medication,
do not spray it directly on the face, but apply it to the
face with a cotton swab or sterile gauze pad. After
using a topical anesthetic on a child, make sure the
child does not get the medicine in his or her mouth.
Topical anesthetics are intended for the temporary relief of pain and itching. They should not be used
for more than a few days at a time. Check with a
doctor if:


the discomfort continues for more than seven days



the problem gets worse



the treated area becomes infected



new signs of irritation, such as skin rash, burning,
stinging, or swelling appear
Dental anesthetics (non-injectable)

Dental anesthetics should not be used if certain
kinds of infections are present. Check package directions or check with a dentist or medical doctor if
uncertain. Dental anesthetics should be used only for
temporary pain relief. If problems such as toothache,
mouth sores, or pain from dentures or braces continue, check with a dentist. Check with a doctor if
sore throat pain is severe, lasts more than two days,
or is accompanied by other symptoms such as fever,
headache, skin rash, swelling, nausea, or vomiting.
Patients should not eat or chew gum while the
mouth is numb from a dental anesthetic. There is a
risk of accidently biting the tongue or the inside of the
mouth. Also nothing should be eaten or drunk for one
hour after applying a dental anesthetic to the back of
the mouth or throat, since the medicine may interfere
with swallowing and may cause choking. If normal
feeling does not return to the mouth within a few
hours after receiving a dental anesthetic or if it is
difficult to open the mouth, check with a dentist.
204

Ophthalmic anesthetics
When anesthetics are used in the eye, it is important not to rub or wipe the eye until the effect of the
anesthetic has worn off and feeling has returned.
Rubbing the eye while it is numb could cause injury.

Side effects
Side effects of regional or local anesthetics vary
depending on the type of anesthetic used and the way it
is administered. Anyone who has unusual symptoms
following the use of an anesthetic should get in touch
with his or her doctor immediately.
There is a small risk of developing a severe headache called a spinal headache following a spinal or
epidural block. This headache is severe when the
patient is upright and hardly felt when the patient
lies down. Though rare, it can occur and can be
treated by performing a blood patch, in which a
small amount of the patient’s own blood is injected
into the area in the back where the anesthetic was
injected. The blood clots and closes up any area that
may have been leaking spinal fluid. Relief is almost
immediate. Finally, blood clots or abscess can form in
the back, but these are also readily treatable and so
pose little risk.
A physician should be notified immediately if any
of these symptoms occur:


large swellings that look like hives on the skin, in the
mouth, or in the throat



severe headache



blurred or double vision



dizziness or lightheadedness



drowsiness



confusion



anxiety, excitement, nervousness, or restlessness



convulsions (seizures)



feeling hot, cold, or numb



ringing or buzzing in the ears



shivering or trembling



sweating



pale skin



slow or irregular heartbeat



breathing problems



nusual weakness or tiredness
GALE ENCYCLOPEDIA OF MEDICINE

Some anesthetic drugs may interact with other
medicines. When this happens, the effects of one or
both of the drugs may change or the risk of side effects
may be greater. Anyone who receives a regional or
local anesthetic should let the doctor know all other
drugs he or she is taking including prescription drugs,
nonprescription drugs, and street drugs (such as
cocaine, marijuana, and heroin).
Resources
BOOKS

Harvey, Richard A., et al., editors. ‘‘Anesthetics.’’ In
Lippincott’s Illustrated Reviews: Pharmacology.
Philadelphia: J.B. Lippincott & Co., 1992.

Nancy Ross-Flanigan

I Aneurysmectomy
Definition
Aneurysmectomy is a surgical procedure performed to repair a weak area in the aorta. The aorta
is the largest artery in the body and the main blood
vessel leading away from the heart.

Purpose
The purpose of aneurysmectomy is to repair an
aortic aneurysm that is likely to rupture if left in place.
Aneurysmectomy is indicated for an aortic aneurysm
that grows to at least 2 in(5 cm) or for an aortic
aneurysm of any size that is symptomatic, tender, or
enlarging rapidly.

Precautions
Aneurysmectomy may not be appropriate for
patients with severely debilitating diseases such as
cancer, emphysema, and heart failure.

Description
An aortic aneurysm is a bulge in the wall of the
aorta that is usually due to arteriosclerosis or atherosclerosis. People who are 50-80 years old are most
likely to develop an aortic aneurysm, with men four
times more likely to develop one than women.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Aneurysm—A weakening in the muscular walls of
a part of the artery which causes the damaged
section to enlarge or sag, giving it a balloon-like
appearance.
Aorta—The main blood vessel that leads away
from the heart and the body’s largest artery. The
aorta carries blood from the heart through the chest
and abdomen, providing major branches to all of
the organs in the body.
Arteriosclerosis—Hardening of the arteries that
occurs as part of the aging process.
Artery—A blood vessel that carries blood from the
heart to the body’s tissues.
Atherosclerosis—A form of arteriosclerosis in
which cholesterol-containing fatty deposits accumulate in the inner most walls of the heart’s
arteries.
Thoracic—Relating to the chest.

An aortic aneurysm develops and grows slowly. It
rarely produces symptoms and is usually only diagnosed by accident during a routine physical exam or
on an x ray or ultrasound done for another reason. As
the aneurysm grows larger, the risk of bursting with no
warning, which causes catastrophic bleeding, rises. A
ruptured aortic aneurysm can cause sudden loss of a
fatal amount of blood within minutes or it can leak in
a series of small bleeds that lead within hours or days
to massive bleeding. A leaking aortic aneurysm that is
not treated is always fatal.
Aneurysmectomy is performed to repair the two
most common types of aortic aneurysms: abdominal
aortic aneurysms that occur in the abdomen below
the kidneys, and thoracic aortic aneurysms that occur
in the chest. It is major surgery performed in a hospital
under general anesthesia and involves removing debris
and then implanting a flexible tube (graft) to replace the
enlarged artery. Aneurysmectomy for an aneurysm of
the ascending aorta (the first part of the aorta that travels
upward from the heart) requires the use of a heart-lung
machine that temporarily stops the heart while the
aneurysm is repaired. Aneurysmectomy requires a
one-week hospital stay; the recovery period is five weeks.
During surgery, the site of the aneurysm (either
the abdomen or the chest) is opened with an incision to
expose the aneurysm. The aorta is clamped above and
below the aneurysm to stop the flow of blood. Then,
205

Aneurysmectomy

Interactions

Angina

an incision is made in the aneurysm. An artificial
Dacron tube is sewn in place above and below the
opened aneurysm, but the aneurysm is not removed.
Plaque or clotted blood are cleaned from the diseased
tissue. The clamps are removed and blood flow is reestablished through the graft. The wall of the aneurysm is wrapped around the graft to protect it and the
skin of the abdomen or chest is sewn up.
Aneurysmectomy can be performed as elective or
emergency surgery. Elective aneurysmectomy takes
about an hour and is far safer than emergency aneurysmectomy, with a mortality rate of 3-5% for elective
abdominal aneurysmectomy and 5-10% for elective
thoracic aneurysmectomy. When an aneurysm
ruptures, 62% of patients die before they reach the
hospital. Of those who make it into emergency aneurysmectromy, 50% die. After a successful aneurysmectomy, the patient has nearly the same life expectancy as
other people of the same age.

Preparation
Before elective aneurysmectomy, blood studies, a
chest x ray, cardiac catherization, electrocardiogram
(ECG), and ultrasound are performed.

Aftercare

I Angina
Definition
Angina is pain, ‘‘discomfort,’’ or pressure localized in the chest that is caused by an insufficient
supply of blood (ischemia) to the heart muscle. It is
also sometimes characterized by a feeling of choking,
suffocation, or crushing heaviness. This condition is
also called angina pectoris.

Description
Often described as a muscle spasm and choking
sensation, the term ‘‘angina’’ is used primarily to
describe chest (thoracic) pain originating from insufficient oxygen to the heart muscle. An episode of angina
is not an actual heart attack, but rather pain that results
from the heart muscle temporarily receiving too little
blood. This temporary condition may be the result of
demanding activities such as exercise and does not
necessarily indicate that the heart muscle is experiencing permanent damage. In fact, episodes of angina
seldom cause permanent damage to heart muscle.
Angina can be subdivided further into two categories: angina of effort and variant angina.
Angina of effort

After aneurysmectomy, the patient is monitored
in an Intensive Care Unit for the first 24–48 hours.
Follow-up tests include ECG, chest x ray, and
ultrasound.

Risks
Elective aneurysmectomy has a 5-10% rate of
complications, such as bleeding, kidney failure,
respiratory complications, heart attack, stroke, infection, limb loss, bowel ischemia, and impotence. These
complications are many times more common in emergency aneurysmectomy.

Angina of effort is a common disorder caused by
the narrowing of the arteries (atherosclerosis) that
supply oxygen-rich blood to the heart muscle. In the
case of angina of effort, the heart (coronary) arteries
can provide the heart muscle (myocardium) adequate
blood during rest but not during periods of exercise,
stress, or excitement–any of which may precipitate
pain. The pain is relieved by resting or by administering nitroglycerin, a medication that reduces ischemia
of the heart. Patients with angina of effort have an
increased risk of heart attack (myocardial infarction).
Variant angina

Resources
PERIODICALS

Donaldson, M. C., M. Belkin, and A. D. Whittemore.
‘‘Mesenteric Revascularization During
Aneurysmectomy.’’ Surgery Clinic of North America 77
(April 1997): 443-459.

Lori De Milto

Variant angina is uncommon and occurs independently of atherosclerosis which may, however, be present as an incidental finding. Variant angina occurs at
rest and is not related to excessive work by the heart
muscle. Research indicates that variant angina is
caused by coronary artery muscle spasm of insufficient
duration or intensity to cause an actual heart attack.

Causes and symptoms

Aneurysms see Aneurysmectomy; Cerebral
aneurysm; Ventricular aneurysm
206

Angina causes a pressing pain or sensation of
heaviness, usually in the chest area under the breast
GALE ENCYCLOPEDIA OF MEDICINE

Ischemia —Decreased blood supply to an organ or
body part, often resulting in pain.
Myocardial infarction —A blockage of a coronary
artery that cuts off the blood supply to part of the
heart. In most cases, the blockage is caused by fatty
deposits.
Myocardium —The thick middle layer of the heart
that forms the bulk of the heart wall and contracts
as the organ beats.

bone (sternum). It occasionally is experienced in the
shoulder, arm, neck, or jaw regions. Because episodes
of angina occur when the heart’s need for oxygen
increases beyond the oxygen available from the
blood nourishing the heart, the condition is often precipitated by physical exertion. In most cases, the symptoms are relieved within a few minutes by resting or by
taking prescribed angina medications. Emotional
stress, extreme temperatures, heavy meals, cigarette
smoking, and alcohol can also cause or contribute to
an episode of angina.

Diagnosis
Physicians can usually diagnose angina based on
the patient’s symptoms and the precipitating factors.
However, other diagnostic testing is often required to
confirm or rule out angina, or to determine the severity of the underlying heart disease.
Electrocardiogram (ECG)
An electrocardiogram is a test that records electrical impulses from the heart. The resulting graph of
electrical activity can show if the heart muscle isn’t
functioning properly as a result of a lack of oxygen.
Electrocardiograms are also useful in investigating
other possible abnormal features of the heart.
Stress test
For many individuals with angina, the results of
an electrocardiogram while at rest will not show any
abnormalities. Because the symptoms of angina occur
during stress, the functioning of the heart may need to
be evaluated under the physical stress of exercise. The
stress test records information from the electrocardiogram before, during, and after exercise in search of
stress-related abnormalities. Blood pressure is also
measured during the stress test and symptoms are
GALE ENCYCLOPEDIA OF MEDICINE

noted. A more involved and complex stress test (for
example, thallium scanning) may be used in some
cases to picture the blood flow in the heart muscle
during the most intense time of exercise and after rest.
Angiogram
The angiogram, which is basically an x ray of the
coronary artery, has been noted to be the most accurate diagnostic test to indicate the presence and extent
of coronary disease. In this procedure, a long, thin,
flexible tube (catheter) is maneuvered into an artery
located in the forearm or groin. This catheter is passed
further through the artery into one of the two major
coronary arteries. A dye is injected at that time to help
the x rays ‘‘see’’ the heart and arteries more clearly.
Many brief x rays are made to create a ‘‘movie’’ of
blood flowing through the coronary arteries, which
will reveal any possible narrowing that causes a
decrease in blood flow to the heart muscle and associated symptoms of angina.

Treatment
Conservative treatment
Artery disease causing angina is addressed initially by controlling existing factors placing the individual at risk. These risk factors include cigarette
smoking, high blood pressure, high cholesterol levels,
and obesity. Angina is often controlled by medication,
most commonly with nitroglycerin. This drug relieves
symptoms of angina by increasing the diameter of the
blood vessels carrying blood to the heart muscle.
Nitroglycerin is taken whenever discomfort occurs or
is expected. It may be taken by mouth by placing the
tablet under the tongue or transdermally by placing a
medicated patch directly on the skin. In addition, beta
blockers or calcium channel blockers may be prescribed
to also decrease the demand on the heart by decreasing
the rate and workload of the heart.
Surgical treatment
When conservative treatments are not effective in
the reduction of angina pain and the risk of heart
attack remains high, physicians may recommend
angioplasty or surgery. Coronary artery bypass surgery is an operation in which a blood vessel (often a
long vein surgically removed from the leg) is grafted
onto the blocked artery to bypass the blocked portion.
This newly formed pathway allows blood to flow adequately to the heart muscle.
Another procedure used to improve blood flow to
the heart is balloon angioplasty. In this procedure, the
207

Angina

KEY TERMS

Angiography

physician inserts a catheter with a tiny balloon at the
end into a forearm or groin artery. The catheter is then
threaded up into the coronary arteries and the balloon
is inflated to open the vessel in narrowed sections.
Other techniques using laser and mechanical devices
are being developed and applied, also by means of
catheters.

Alternative treatment
During an angina episode, relief has been noted by
applying massage or kinesiological methods, but these
techniques are not standard recommendations by physicians. For example, one technique places the palm
and fingers of either hand on the forehead while simultaneously firmly massaging the sternum (breast bone)
up and down its entire length using the other hand.
This is followed by additional massaging by the fingertip and thumb next to the sternum, on each side.
Once the angina has subsided, the cause should be
determined and treated. Atherosclerosis, a major associated cause, requires diet and lifestyle adjustments,
primarily including regular exercise, reduction of dietary sugar and saturated fats, and increase of dietary
fiber. Both conventional and alternative medicine
agree that increasing exercise and improving diet are
important steps to reduce high cholesterol levels.
Alternative medicine has proposed specific cholesterol-lowering treatments, with several gaining the
attention and interest of the public. One of the most
recent popular treatments is garlic (Allium sativum).
Some studies have shown that adequate dosages of
garlic can reduce total cholesterol by about 10%,
LDL (bad) cholesterol by 15%, and raise HDL
(good) cholesterol by 10%. Other studies have not
shown significant benefit. Although its effect on cholesterol is not as great as that achieved by medications,
garlic may possibly be of benefit in relatively mild
cases of high cholesterol, without causing the side
effects associated with cholesterol-reducing drugs.
Other herbal remedies that may help lower cholesterol
include alfalfa (Medicago sativa), fenugreek
(Trigonella foenum-graecum), Asian ginseng (Panax
ginseng), and tumeric (Curcuma longa).
Antioxidants, including vitamin A (beta carotene),
vitamin C, vitamin E, and selenium, can limit the oxidative damage to the walls of blood vessels that may
be a precursor of atherosclerotic plaque formation.

Prognosis
The prognosis for a patient with angina depends
on its origin, type, severity, and the general health of
208

the individual. A person who has angina has the best
prognosis if he or she seeks prompt medical attention
and learns the pattern of his or her angina, such as
what causes the attacks, what they feel like, how long
episodes usually last, and whether medication relieves
the attacks. If patterns of the symptoms change significantly, or if symptoms resemble those of a heart
attack, medical help should be sought immediately.

Prevention
In most cases, the best prevention involves changing one’s habits to avoid bringing on attacks of
angina. If blood pressure medication has been prescribed, compliance is a necessity and should be a
priority as well. Many healthcare professionals–
including physicians, dietitians, and nurses–can provide valuable advice on proper diet, weight control,
blood cholesterol levels, and blood pressure. These
professionals also offer suggestions about current
treatments and information to help stop smoking. In
general, the majority of those with angina adjust their
lives to minimize episodes of angina, by taking necessary precautions and using medications if recommended and necessary. Coronary artery disease is the
underlying problem that should be addressed.
Resources
ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
OTHER

‘‘Angina.’’ Healthtouch Online Page. Sepember 1997. [cited
May 21, 1998]. <http://www.healthtouch.com>.

Jeffrey P. Larson, RPT

Angioedema see Hives
Angiogram see Angiography

I Angiography
Definition
Angiography is the x-ray study of the blood
vessels. An angiogram uses a radiopaque substance,
or dye, to make the blood vessels visible under x ray.
Arteriography is a type of angiography that involves
the study of the arteries.
GALE ENCYCLOPEDIA OF MEDICINE

Angiography is used to detect abnormalities or
blockages in the blood vessels (called occlusions)
throughout the circulatory system and in some organs.
The procedure is commonly used to identify atherosclerosis; to diagnose heart disease; to evaluate kidney function
and detect kidney cysts or tumors; to detect an aneurysm
(an abnormal bulge of an artery that can rupture leading
to hemorrhage), tumor, blood clot, or arteriovenous malformations (abnormals tangles of arteries and veins) in
the brain; and to diagnose problems with the retina of the
eye. It is also used to give surgeons an accurate ‘‘map’’ of
the heart prior to open-heart surgery, or of the brain prior
to neurosurgery.

Precautions

An angiogram of a coronary artery. (Phototake NYC. Reproduced
by permission.)

Patients with kidney disease or injury may suffer
further kidney damage from the contrast mediums
used for angiography. Patients who have blood clotting problems, have a known allergy to contrast mediums, or are allergic to iodine, a component of some
contrast mediums, may also not be suitable candidates
for an angiography procedure. Because x rays carry

KEY TERMS
Arteriosclerosis—A chronic condition characterized
by thickening and hardening of the arteries and
the build-up of plaque on the arterial walls.
Arteriosclerosis can slow or impair blood circulation.
Carotid artery—An artery located in the neck.
Catheter—A long, thin, flexible tube used in angiography to inject contrast material into the arteries.
Cirrhosis—A condition characterized by the destruction of healthy liver tissue. A cirrhotic liver is scarred
and cannot break down the proteins in the bloodstream. Cirrhosis is associated with portal hypertension.
Embolism—A blood clot, air bubble, or clot of foreign
material that travels and blocks the flow of blood in an
artery. When blood supply to a tissue or organ is
blocked by an embolism, infarction, or death of the
tissue the artery feeds, occurs. Without immediate
and appropriate treatment, an embolism can be fatal.
Femoral artery—An artery located in the groin area
that is the most frequently accessed site for arterial
puncture in angiography.
Fluorescein dye—An orange dye used to illuminate the
blood vessels of the retina in fluorescein angiography.

GALE ENCYCLOPEDIA OF MEDICINE

Fluoroscopic screen—A fluorescent screen which
displays ‘‘moving x-rays’’ of the body. Fluoroscopy
allows the radiologist to visualize the guide wire and
catheter he is moving through the patient’s artery.
Guide wire—A wire that is inserted into an artery to
guides a catheter to a certain location in the body.
Iscehmia—A lack of normal blood supply to a organ
or body part because of blockages or constriction of
the blood vessels.
Necrosis—Cellular or tissue death; skin necrosis
may be caused by multiple, consecutive doses of
radiation from fluoroscopic or x-ray procedures.
Plaque—Fatty material that is deposited on the
inside of the arterial wall.
Portal hypertension—A condition caused by cirrhosis
of the liver. It is characterized by impaired or reversed
blood flow from the portal vein to the liver, an enlarged
spleen, and dilated veins in the esophagus and stomach.
Portal vein thrombosis—The development of a
blood clot in the vein that brings blood into the
liver. Untreated portal vein thrombosis causes portal
hypertension.

209

Angiography

Purpose

Angiography

risks of ionizing radiation exposure to the fetus, pregnant women are also advised to avoid this procedure.

Description
Angiography is usually performed at a hospital by
a trained radiologist and assisting technician or nurse.
It takes place in an x-ray or fluoroscopy suite, and for
most types of angiograms, the patient’s vital signs will
be monitored throughout the procedure.
Angiography requires the injection of a contrast dye
that makes the blood vessels visible to x ray. The dye is
injected through a procedure known as arterial puncture.
The puncture is usually made in the groin area, armpit,
inside elbow, or neck. The site is cleaned with an antiseptic agent and injected with a local anesthetic. First, a
small incision is made in the skin to help the needle pass.
A needle containing an inner wire called a stylet is
inserted through the skin into the artery. When the radiologist has punctured the artery with the needle, the
stylet is removed and replaced with another long wire
called a guide wire. It is normal for blood to spout out of
the needle before the guide wire is inserted.
The guide wire is fed through the outer needle into
the artery and to the area that requires angiographic
study. A fluoroscopic screen that displays a view of the
patient’s vascular system is used to pilot the wire to the
correct location. Once it is in position, the needle is
removed and a catheter is slid over the length of the
guide wire until it to reaches the area of study. The
guide wire is removed and the catheter is left in place in
preparation for the injection of the contrast medium,
or dye.
Depending on the type of angiography procedure
being performed, the contrast medium is either injected
by hand with a syringe or is mechanically injected with
an automatic injector connected to the catheter. An
automatic injector is used frequently because it is able
to propel a large volume of dye very quickly to the
angiogram site. The patient is warned that the injection
will start, and instructed to remain very still. The injection causes some mild to moderate discomfort. Possible
side effects or reactions include headache, dizziness,
irregular heartbeat, nausea, warmth, burning sensation, and chest pain, but they usually last only momentarily. To view the area of study from different angles
or perspectives, the patient may be asked to change
positions several times, and subsequent dye injections
may be administered. During any injection, the patient
or the camera may move.
Throughout the dye injection procedure, x-ray
pictures and/or fluoroscopic pictures (or moving
210

x rays) will be taken. Because of the high pressure of
arterial blood flow, the dye will dissipate through the
patient’s system quickly, so pictures must be taken in
rapid succession. An automatic film changer is used
because the manual changing of x-ray plates can eat up
valuable time.
Once the x rays are complete, the catheter is slowly
and carefully removed from the patient. Pressure is
applied to the site with a sandbag or other weight for
10-20 minutes in order for clotting to take place and
the arterial puncture to reseal itself. A pressure bandage is then applied.
Most angiograms follow the general procedures
outlined above, but vary slightly depending on the
area of the vascular system being studied. A variety
of common angiography procedures are outlined
below:
Cerebral angiography
Cerebral angiography is used to detect aneurysms,
blood clots, and other vascular irregularities in the
brain. The catheter is inserted into the femoral or
carotid artery and the injected contrast medium travels through the blood vessels on the brain. Patients
frequently experience headache, warmth, or a burning
sensation in the head or neck during the injection
portion of the procedure. A cerebral angiogram
takes two to four hours to complete.
Coronary angiography
Coronary angiography is administered by a cardiologist with training in radiology or, occasionally,
by a radiologist. The arterial puncture is typically
given in the femoral artery, and the cardiologist uses
a guide wire and catheter to perform a contrast injection and x-ray series on the coronary arteries. The
catheter may also be placed in the left ventricle to
examine the mitral and aortic valves of the heart. If
the cardiologist requires a view of the right ventricle of
the heart or of the tricuspid or pulmonic valves, the
catheter will be inserted through a large vein and
guided into the right ventricle. The catheter also serves
the purpose of monitoring blood pressures in these
different locations inside the heart. The angiogram
procedure takes several hours, depending on the complexity of the procedure.
Pulmonary angiography
Pulmonary, or lung, angiography is performed to
evaluate blood circulation to the lungs. It is also considered the most accurate diagnostic test for detecting
a pulmonary embolism. The procedure differs from
GALE ENCYCLOPEDIA OF MEDICINE

Kidney angiography
Patients with chronic renal disease or injury can
suffer further damage to their kidneys from the contrast medium used in a kidney angiogram, yet they
often require the test to evaluate kidney function.
These patients should be well-hydrated with a intravenous saline drip before the procedure, and may benefit
from available medications (e.g., dopamine) that help
to protect the kidney from further injury due to contrast agents. During a kidney angiogram, the guide
wire and catheter are inserted into the femoral artery
in the groin area and advanced through the abdominal
aorta, the main artery in the abdomen, and into the
renal arteries. The procedure will take approximately
one hour.
Fluorescein angiography
Fluorescein angiography is used to diagnose retinal problems and circulatory disorders. It is typically
conducted as an outpatient procedure. The patient’s
pupils are dilated with eye drops and he rests his chin
and forehead against a bracing apparatus to keep it
still. Sodium fluorescein dye is then injected with a
syringe into a vein in the patient’s arm. The dye will
travel through the patient’s body and into the blood
vessels of the eye. The procedure does not require
x rays. Instead, a rapid series of close-up photographs
of the patient’s eyes are taken, one set immediately
after the dye is injected, and a second set approximately 20 minutes later once the dye has moved
through the patient’s vascular system. The entire
procedure takes up to one hour.
Celiac and mesenteric angiography
Celiac and mesenteric angiography involves x-ray
exploration of the celiac and mesenteric arteries, arterial branches of the abdominal aorta that supply blood
to the abdomen and digestive system. The test is commonly used to detect aneurysm, thrombosis, and signs
of ischemia in the celiac and mesenteric arteries, and to
locate the source of gastrointestinal bleeding. It is also
GALE ENCYCLOPEDIA OF MEDICINE

used in the diagnosis of a number of conditions,
including portal hypertension, and cirrhosis. The procedure can take up to three hours, depending on the
number of blood vessels studied.
Splenoportography
A splenoportograph is a variation of an angiogram that involves the injection of contrast medium
directly into the spleen to view the splenic and portal
veins. It is used to diagnose blockages in the splenic
vein and portal vein thrombosis and to assess the
strength and location of the vascular system prior to
liver transplantation.
Most angiography procedures are typically paid
for by major medical insurance. Patients should check
with their individual insurance plans to determine
their coverage.

Preparation
Patients undergoing an angiogram are advised to
stop eating and drinking eight hours prior to the procedure. They must remove all jewelry before the procedure and change into a hospital gown. If the arterial
puncture is to be made in the armpit or groin area,
shaving may be required. A sedative may be administered to relax the patient for the procedure. An IV line
will also be inserted into a vein in the patient’s arm
before the procedure begins in case medication or
blood products are required during the angiogram.
Prior to the angiography procedure, patients will
be briefed on the details of the test, the benefits and
risks, and the possible complications involved, and
asked to sign an informed consent form.

Aftercare
Because life-threatening internal bleeding is a possible complication of an arterial puncture, an overnight stay in the hospital is sometimes recommended
following an angiography procedure, particularly with
cerebral and coronary angiograms. If the procedure is
performed on an outpatient basis, the patient is typically kept under close observation for a period of at six
to 12 hours before being released. If the arterial puncture was performed in the femoral artery, the patient
will be instructed to keep his leg straight and relatively
immobile during the observation period. The patient’s
blood pressure and vital signs will be monitored and
the puncture site observed closely. Pain medication
may be prescribed if the patient is experiencing discomfort from the puncture, and a cold pack is applied
to the site to reduce swelling. It is normal for the
211

Angiography

cerebral and coronary angiograms in that the guide
wire and catheter are inserted into a vein instead of an
artery, and are guided up through the chambers of the
heart and into the pulmonary artery. Throughout the
procedure, the patient’s vital signs are monitored to
ensure that the catheter doesn’t cause arrhythmias, or
irregular heartbeats. The contrast medium is then
injected into the pulmonary artery where it circulates
through the lung capillaries. The test typically takes up
to 90 minutes.

Angioplasty

puncture site to be sore and bruised for several weeks.
The patient may also develop a hematoma, a hard
mass created by the blood vessels broken during the
procedure. Hematomas should be watched carefully,
as they may indicate continued bleeding of the arterial
puncture site.
Angiography patients are also advised to enjoy
two to three days of rest and relaxation after the
procedure in order to avoid placing any undue stress
on the arterial puncture. Patients who experience continued bleeding or abnormal swelling of the puncture
site, sudden dizziness, or chest pains in the days following an angiography procedure should seek medical
attention immediately.
Patients undergoing a fluorescein angiography
should not drive or expose their eyes to direct sunlight
for 12 hours following the procedure.

Risks
Because angiography involves puncturing an
artery, internal bleeding or hemorrhage are possible
complications of the test. As with any invasive procedure, infection of the puncture site or bloodstream is
also a risk, but this is rare.
A stroke or heart attack may be triggered by an
angiogram if blood clots or plaque on the inside of the
arterial wall are dislodged by the catheter and form a
blockage in the blood vessels or artery. The heart may
also become irritated by the movement of the catheter
through its chambers during pulmonary and coronary
angiography procedures, and arrhythmias may develop.
Patients who develop an allergic reaction to the
contrast medium used in angiography may experience
a variety of symptoms, including swelling, difficulty
breathing, heart failure, or a sudden drop in blood
pressure. If the patient is aware of the allergy before
the test is administered, certain medications can be
administered at that time to counteract the reaction.
Angiography involves minor exposure to radiation through the x rays and fluoroscopic guidance
used in the procedure. Unless the patient is pregnant,
or multiple radiological or fluoroscopic studies are
required, the small dose of radiation incurred during
a single procedure poses little risk. However, multiple
studies requiring fluoroscopic exposure that are conducted in a short time period have been known to
cause skin necrosis in some individuals. This risk can
be minimized by careful monitoring and documentation of cumulative radiation doses administered to
these patients.

212

Normal results
The results of an angiogram or arteriogram
depend on the artery or organ system being examined. Generally, test results should display a normal
and unimpeded flow of blood through the vascular
system. Fluorescein angiography should result in no
leakage of fluorescein dye through the retinal blood
vessels.

Abnormal results
Abnormal results of an angiography may display
a restricted blood vessel or arterial blood flow (ischemia) or an irregular placement or location of blood
vessels. The results of an angiography vary widely by
the type of procedure performed, and should be interpreted and explained to the patient by a trained
radiologist.
Resources
BOOKS

Baum, Stanley, and Michael J. Pentecost, editors. Abrams’
Angiography. 4th ed. Philadelphia: Lippincott-Raven,
1996.

Paula Anne Ford-Martin

Angiomas see Birthmarks

I Angioplasty
Definition
Angioplasty is a term describing a procedure used
to widen vessels narrowed by stenoses or occlusions.
There are various types of these procedures and their
names are associated with the type of vessel entry and
equipment used. For example, percutaneous transluminal angioplasty (PTA) describes entry through
the skin (percutaneous) and navigates to the area of
the vessel of interest through the same vessel or one
that communicates with it (transluminal). In the case
of a procedure involving the coronary arteries, the
point of entry could be the femoral artery in the
groin and the catheter/guidewire system is passed
through the aorta to the heart and the origin of the
coronary arteries at the base of the aorta just outside
the aortic valve.

GALE ENCYCLOPEDIA OF MEDICINE

Angioplasty

Angioplasty
Before

Inflated
balloon

After

Guidewire
Improved
flow

Inadequate
flow

Lumen

Plaque

In balloon angioplasty, plaque is pushed out of the clogged artery by the inflation of the balloon device. (Illustration by Argosy Inc.)

Purpose
In individuals with an occulsive vascular disease
such as atherosclerosis, blood flow is impaired to an
organ (such as the heart) or to a distal body part ( such
as the lower leg) by the narrowing of the vessel’s lumen
due to fatty deposits or calcium accumulation. This
narrowing may occur in any vessel but may occur
anywhere. Once the vessel has been widened, adequate
blood flow is returned. The vessel may narrow again
over time at the same location and the procedure could
be repeated.

KEY TERMS
plaque—In atherosclerosis, a swollen area in the
lining of an artery formed by fatty deposits.
cardiac catheterization—A procedure to pass a
catheter to the heart and its vessels for the purpose
of diagnosing coronary artery disease, assessing injury
or disease of the aorta, or evaluating cardiac function.
EKG—Electrocardiogram, used to study and record
the electrical activity of the heart.

Precautions
Angioplasty procedures are performed on hospital inpatients in facilities for proper monitoring
and recovery. If the procedure is to be performed
in a coronary artery, the patient’s care is likely to
be provided by specially trained physicians, nurses,
and vascular specialists. Typically, patients are
given anticoagulants prior to the procedure to
assist in the prevention of thromboses (blood clots).
Administration of anticoagulants, however, may
impede the sealing of the vascular entry point. The
procedure will be performed using fluoroscopic guidance and contrast media. Since the decision to perform angioplasty may have been made following a
diagnostic angiogram, the patient’s sensitivity to iodinated contrast media is likely to known. The procedure may then require the use of non-ionic contrast
agents.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Angioplasty was originally performed by dilating
the vessel with the introduction of larger and larger
stiff catheters through the narrowed space.
Complications of this procedure caused researchers
to develop means of widening the vessel using a minimally sized device. Today, catheters contain balloons
that are inflated to widen the vessel and stents to
provide structural support for the vessel. Lasers may
be used to assist in the break up of the fat or calcium
plaque. Catheters may also be equipped with spinning
wires or drill tips to clean out the plaque.
Angioplasty may be performed while the patient is
sedated or anesthetized, depending on the vessels
involved. If a percutaneous transluminal coronary
angioplasty (PTCA) is to be performed, the patient
213

Angiotensin-converting enzyme inhibitors

will be kept awake to report on discomfort and cough
if required. PTCA procedures are performed in cardiac catheterization labs with sophisticated monitoring
devices. If angioplasty is performed in the radiology
department’s angiographic suite, the patient may be
sedated for the procedure and a nurse will monitor
the patient’s vital signs during the procedure. If performed by a vascular surgeon, the angioplasty procedure will be performed in an operating room or
specially designed vascular procedure suite.
The site of the introduction of the angioplasty
equipment is prepared as a sterile surgical site.
Although many procedures are performed by puncturing the vessel through skin, many procedures are also
performed by surgically exposing the site of entry.
Direct view of the vessel’s puncture site aids in monitoring damage to the vessel or excessive bleeding at
the site. Once the vessel is punctured and the guidewire
is introduced, fluoroscopy is used to monitor small
injections of contrast media used to visualize the path
through the vessel. If the fluoroscopy system has a
feature called ‘roadmap’, the amount of contrast
media injected will be greater in order to define the full
route the guidewire will take. The fluoroscopy system
will then superimpose subsequent images over the roadmap while the vessel is traversed, that is, the physician
moves the guidewire along the map to the destination.
Having reached the area of stenosis, the physician
will inflate the balloon on the catheter that has been
passed along the guidewire. Balloons are inflated in size
and duration depending on the size and location of the
vessel. In some cases, the use of a stent (a mesh of wire
that resembles a Chinese finger puzzle) may also be
used. The vessel may be widened before, during, or
after the deployment of the stent. Procedures for deploying stents are dependent on the type of stent used. In
cases where the vessel is tortuous or at intersections of
vessels, the use of a graph may be necessary to provide
structural strength to the vessel. Stents, graphs, and
balloon dilation may all be used together or separately.
The procedure is verified using fluoroscopy and
contrast media to produce an angiogram or by using
intravascular ultrasound or both. All equipment is
withdrawn from the vessel and the puncture site
repaired.

Risks
During the procedure there is a danger of puncturing the vessel with the guidewire. This is a very
small risk. Patients must be monitored for hematoma
or hemorrhage at the puncture site. There is also a
small risk of heart attack, emboli, and although
214

unlikely death. Hospitalization will vary in length by
the patient’s overall condition, any complications, and
availability of home care.
Resources
PERIODICALS

‘‘The angioplasty correct follow up strategy after stent
implantation.’’ Heart 84, no. 4 (April, 2001): 363.
Carnall, Douglas. ‘‘Angioplasty.’’ The Western Journal of
Medicine 173, no. 3 (September 2000): 201.
‘‘New Imaging Technique Could Improve Outcome of
Popular Heart Procedure.’’ Heart Disease Weekly May
13, 2001: 3.
‘‘Success clearing clogged arteries.’’ Science News 159, no. 5
(February 3, 2001): 72.
OTHER

‘‘Cardiovascular System’’ Miami Heart Research
Institute 2001. [cited July 5, 2001]. <http://www.
miamiheartresearch.org/Learning Center/Your
Cardiovascular.../Cardiovascular.htm>.
‘‘Coronary angioplasty: Opening clogged arteries’’
MayoClinic.com, Condition Centers, Treatments and
Tests. 2000. [cited July 5, 2001]. <http://
www.mayoclinic.com>.
‘‘Heart American Heart Association online. 2000. [cited July
5, 2001]. <http://www.americanheart.org/
Heart_and_Stroke_A_Z_Guide/angiol.html>.
‘‘STS Patient Information: What to Expect after your Heart
Surgery.’’ Society of Thoracic Surgeons online. 2000.
[cited July 5, 2001]. <http://www.sts.org/doc/3563>.
‘‘When you need to have Angioplast: A patient guide’’ Heart
Information Network. 2000. [cited July 5, 2001].
<http://www.heartinfo.org/news97/
gdangio111897.htm>.

Elaine R. Proseus, MBA/TM, BSRT, RT(R)

I Angiotensin-converting
enzyme inhibitors
Definition
Angiotensin-converting enzyme inhibitors (also
called ACE inhibitors) are medicines that block the
conversion of the chemical angiotensin I to a substance
that increases salt and water retention in the body.

Purpose
ACE inhibitors are used in the treatment of high
blood pressure. They may be used alone or in combination with other medicines for high blood pressure.
GALE ENCYCLOPEDIA OF MEDICINE

Arteries—Blood vessels that carry blood away from
the heart to the cells, tissues, and organs of the
body.
Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Enzyme—A type of protein, produced in the body,
that brings about or speeds up chemical reactions.
Fetus—A developing baby inside the womb.
Scleroderma—A disease that first affects the skin
and later affects certain internal organs. The first
symptoms are the hardening, thickening, and
shrinking of the skin.
Systemic lupus erythematosus (SLE)—A chronic
disease that affects the skin, joints, and certain
internal organs.
Venom—A poisonous substance secreted by an
animal, usually delivered through a bite or a sting.

They work by preventing a chemical in the blood,
angiotensin I, from being converted into a substance
that increases salt and water retention in the body.
Increased salt and water retention lead to high blood
pressure. ACE inhibitors also make blood vessels
relax, which helps lower blood pressure and allows
more oxygen-rich blood to reach the heart.
Treating high blood pressure is important because
the condition puts a burden on the heart and the
arteries, which can lead to permanent damage over
time. If untreated, high blood pressure increases the
risk of heart attacks, heart failure, stroke, or kidney
failure.
ACE inhibitors may also be prescribed for other
conditions. For example, captopril (Capoten) is used
to treat kidney problems in people who take insulin to
control diabetes. Captopril and lisinopril are also
given to some patients after a heart attack. Heart
attacks damage and weaken the heart muscle, and
the damage continues even after a person recovers
from the attack. This medicine helps slow down
further damage to the heart. ACE inhibitors also
may be used to treat congestive heart failure.

Description
ACE inhibitors are available only with a physician’s prescription and come in tablet, capsule, and
GALE ENCYCLOPEDIA OF MEDICINE

injectable forms. Some commonly used ACE inhibitors are benazepril (Lotensin), captopril (Capoten),
enalapril (Vasotec), fosinopril (Monopril), lisinopril
(Prinivil, Zestril), moexipril (Univasc), perindopril
(Aceon), quinapril (Accupril), ramipril (Altace) and
trandolapril (Mavik).

Recommended dosage
The recommended dosage depends on the type of
ACE inhibitor and the medical condition for which
it is being taken. Check with the physician who
prescribed the drug or the pharmacist who filled the
prescription for the correct dosage.
This medicine may take weeks to noticeably lower
blood pressure. Take it exactly as directed.
Do not stop taking this medicine without checking with the physician who prescribed it.

Precautions
A person taking an ACE inhibitor should see a
physician regularly. The physician will check the
blood pressure to make sure the medicine is working
as it should and will note any unwanted side effects.
People who have high blood pressure often feel perfectly fine. However, they should continue to see their
physicians even when they feel well so that the physician can keep a close watch on their condition. It is
also important for patients to keep taking their medicine even when they feel fine.
ACE inhibitors will not cure high blood pressure,
but will help control the condition. To avoid the serious health problems that high blood pressure can
cause, patients may have to take medicine for the rest
of their lives. Furthermore, medicine alone may not be
enough. Patients with high blood pressure may also
need to avoid certain foods, such as salty snacks, and
keep their weight under control. The health care professional who is treating the condition can offer advice
on what measures may be necessary. Patients being
treated for high blood pressure should not change
their diets without consulting their physicians.
Anyone taking this medicine for high blood pressure should not take any other prescription or overthe-counter (OTC) medicine without first checking
with his or her physician. Some medicines, such as
certain cold remedies, may increase blood pressure.
Some people feel dizzy or lightheaded after taking
the first dose of an ACE inhibitor, especially if they
have been taking a water pill (diuretic). Anyone who
takes these drugs should not drive, use machines or do
215

Angiotensin-converting enzyme inhibitors

KEY TERMS

Angiotensin-converting enzyme inhibitors

anything else that might be dangerous until they have
found out how the drugs affect them. Such symptoms
should be reported to the physician or pharmacist if
they do not subside within a day or so. For the first one
or two days of taking an ACE inhibitor, patients may
become lightheaded when arising from bed in the
morning. Patienst should rise slowly to a sitting position before standing up.
While a goal of treatment with an ACE inhibitor
is to lower the blood pressure, patients must be careful
not to let their blood pressure get too low. Low blood
pressure can lead to dizziness, lightheadedness and
fainting. To prevent the blood pressure from getting
too low, observe these precautions:


Do not drink alcohol without checking with the
physician who prescribed this medicine.



Captopril and moexipril should be taken one hour
before meals. Other ACE inhinbitors may be taken
with or without meals.



Avoid overheating when exercising or in hot
weather. The loss of water from the body through
heavy sweating can cause low blood pressure.



Check with a physician right away if illness occurs
while taking an ACE inhibitor. This is especially true
if the illness involves severe nausea, vomiting, or diarrhea. Vomiting and diarrhea can cause the loss of too
much water from the body, which can lead to low
blood pressure.

Anyone who is taking ACE inhibitors should be
sure to tell the health care professional in charge
before having any surgical or dental procedures or
receiving emergency treatment.
Some ACE inhibitors may change the results of
certain medical tests, such as blood or urine tests.
Before having medical tests, anyone taking this medicine should alert the health care professional in charge.
Do not use a potassium supplement or a salt substitute that contains potassium without first checking
with the physician who prescribed the ACE inhibitor.
Patients who are being treated with bee or wasp
venom to prevent allergic reactions to stings may have
a severe allergic reaction to certain ACE inhibitors.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take ACE inhibitors. Before taking these drugs,
be sure to let the physician know about any of these
conditions.
216

ALLERGIES. Anyone who has had unusual reactions to an ACE inhibitor in the past should let his
or her physician know before taking this type of medicine again. The physician should also be told about
any allergies to foods, dyes, preservatives, or other
substances.
PREGNANCY. The use of ACE inhibitors in pregnancy can cause serious problems and even death in the
fetus or newborn. Women who are pregnant or who
may become pregnant should check with their physicians before using this medicine. Women who become
pregnant while taking this medicine should check with
their physicians immediately.
BREASTFEEDING. Some ACE inhibitors pass into
breast milk. Women who are breastfeeding should
check with their physicians before using ACE
inhibitors.
OTHER MEDICAL CONDITIONS. Before using ACE
inhibitors, people with any of these medical problems
should make sure their physicians are aware of their
conditions:


diabetes



heart or blood vessel disease



recent heart attack or stroke



liver disease



kidney disease



kidney transplant



scleroderma



systemic lupus erythematosus (SLE)

USE OF CERTAIN MEDICINES. Taking ACE inhibitors with certain other drugs may affect the way the
drugs work or may increase the chance of side
effects.

Side effects
The most common side effect is a dry, continuing
cough. This usually does not subside unless the medication is stopped. Ask the physician if the cough can
be treated. Less common side effects, such as headache, loss of taste, unusual tiredness, and nausea or
diarrhea also may occur and do not need medical
attention unless they are severe or they interfere with
normal activities.
More serious side effects are rare, but may occur.
If any of the following side effects occur, check with a
physician immediately:


swelling of the face, lips, tongue, throat, arms, legs,
hands, or feet
GALE ENCYCLOPEDIA OF MEDICINE

itchy skin



sudden breathing or swallowing problems



chest pain



hoarseness



sore throat



fever and chills



stomach pain



yellow eyes or skin

In addition, anyone who has any of the following symptoms while taking an ACE inhibitor
should check with his or her physician as soon as
possible:


dizziness, lightheadedness, fainting



confusion



nervousness



fever



joint pain



numbness or tingling in hands, feet, or lips



weak or heavy feeling in the legs



skin rash



irregular heartbeat



shortness of breath or other breathing problems

Other side effects may occur. Anyone who has
unusual symptoms after taking an ACE inhibitor
should get in touch with his or her physician.

Interactions
ACE inhibitors may interact with certain foods
and other medicines. For example, captopril
(Capoten) interacts with food and should be taken
one hour before meals. Anyone who takes ACE inhibitors should let the physician know all other medicines he or she is taking and should ask about foods
that should be avoided. Among the foods and drugs
that may interact with ACE inhibitors are:


water pills (diuretics)



lithium, used to treat bipolar disorder



tetracycline, an antibiotic



medicines or supplements that contain potassium



salt substitutes that contain potassium

The list above may not include everything that
interacts with ACE inhibitors. Be sure to check with
a physician or pharmacist before combining ACE
GALE ENCYCLOPEDIA OF MEDICINE

inhibitors with any other prescription or nonprescription (over-the-counter) medicine.
Nancy Ross-Flanigan

I Angiotensin-converting
enzyme test
Definition
This test measures blood levels of angiotensinconverting enzyme (ACE), also known as Serum
Angiotensin-Converting Enzyme (SASE). The primary function of ACE is to help regulate arterial
pressure by converting angiotensin I to angiotensin II.

Purpose
The ACE test is used primarily to detect and
monitor the clinical course of sarcoidosis (a disease
that affects many organs, especially the lungs), to differentiate between sarcoidosis and similar diseases, and to
delineate between active and inactive sarcoid disease.
Elevated ACE levels are also found in a number of
other conditions, including Gaucher’s disease (a rare
familial disorder of fat metabolism) and leprosy.

Precautions
It should be noted that people under 20 years of
age normally have very high ACE levels. Decreased
levels may be seen in the condition of excess fat in the
blood (hyperlipidemia). Drugs that may cause
decreased ACE levels include ACE inhibitor antihypertensives and steroids.

Description
ACE plays an important role in the renin/aldosterone mechanism which controls blood pressure by
converting angiotensin I to angiotensin II, two proteins involved in regulating blood pressure.
Angiotensin I by itself is inactive, but when converted
by ACE to the active form, angiotensin II, it causes
narrowing of the small blood vessels in tissues, resulting in an increase in blood pressure. Angiotensin II
also stimulates the hormone aldosterone, which causes
an increase in blood pressure. Certain kidney disorders increase the production of angiotensin II, another
cause of hypertension. Despite the action of ACE on
blood pressure regulation, determination of this
217

Angiotensin-converting enzyme test



Animal bite infections

KEY TERMS
Sarcoidosis—Sarcoidosis is a rare disease of
unknown cause in which inflammation occurs in
lymph nodes and other tissues throughout the
body, usually the lungs, skin, liver, and eyes.

enzyme is not very helpful in the evaluation of hypertension (high blood pressure).

Preparation
Determination of ACE levels requires a blood
sample. The patient need not be fasting.

Risks
Risks for this test are minimal, but may include
slight bleeding from the puncture site, fainting or
feeling lightheaded after venipuncture, or hematoma
(blood accumulating under the puncture site).

Normal results
Normal ranges for this test are laboratory-specific
but can range from 8-57 U/ml for patients over
20 years of age.

Abnormal results
Serum ACE levels are elevated in approximately
80-90% of patients with active sarcoidosis. Thyroid hormone may have an effect on ACE activity, as hypothyroid (low thyroid) patients, as well as patients with
anorexia nervosa with associated findings of hypothyroidism, may have low serum ACE activity. ACE can also be
decreased in lung cancer (bronchogenic carcinoma).
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

I Animal bite infections
Definition
The most common problem following an animal
bite is simple infection. The saliva of dogs, cats, ferrets,
218

and rabbits is known to contain a wide variety of
bacteria. According to one recent study, bacteria or
other pathogens show up in about 85 percent of bites.
When an animal bites, it can then transmit pathogens
into the wound. These microorganisms may grow
within the wound and cause an infection. The consequences of infection range from mild discomfort to
life-threatening complications.

Description
Two to 4.5 million animal bites occur each year in
the United States; about 1% of these bites require
hospitalization. Animal bites result in 334,000 emergency room visits per year, which represents approximately 1% of all emergency hospital visits, at an
annual cost of $100 million dollars in health care
expenses and lost income. Children are the most frequent victims of dog bites, with 5–9 year-old boys
having the highest incidence. Men are more often
bitten by dogs than are women (3:1), whereas women
are more often bitten by cats (3:1).
Dog bites make up 80–85% of all reported incidents. Cats account for about 10% of reported bites,
and other animals (including hamsters, ferrets, rabbits, horses, raccoons, bats, skunks, and monkeys)
make up the remaining 5–10%. Cat bites become
infected more frequently than dog bites. A dog’s
mouth is rich in bacteria, but only 15–20% of dog
bites become infected. In contrast, approximately
30–50% of cat bites become infected.
Many factors contribute to the infection rates,
including the type of wound inflicted, the location of
the wound, pre-existing health conditions in the bitten
person, the extent of delay before treatment, patient
compliance and the presence of a foreign body in the
wound. Dogs usually inflict crush injuries because
they have rounded teeth and strong jaws; thus, the
bite of an adult dog can exert up to 200 pounds per
square inch of pressure. This pressure usually results in
a crushing injury, causing damage to such deep structures as bones, blood vessels, tendons, muscles, and
nerves. The canine teeth in a dog’s mouth are also
sharp and strong, often inflicting lacerations. Cats,
with their needle-like incisors and carnassial teeth,
typically cause puncture wounds. Puncture wounds
appear innocuous on the surface, but the underlying
injury goes deep. Cat teeth essentially inject bacteria
into the bite, and the deep, narrow wound is difficult
to clean. Persons with impaired immunocompetence—for example, individuals with HIV infection—are especially vulnerable to infection from cat
bites. Lastly, bites or stings from marine creatures
GALE ENCYCLOPEDIA OF MEDICINE

Anaerobic—Referring to an organism that can live
in the absence of air or oxygen. About two-thirds of
animal bites are found to contain anaerobic disease-producing organisms.
Canines—The two sharp teeth located next to the
front incisor teeth in mammals that are used to grip
and tear.
Carnassials—The last upper premolar teeth in the
mouths of cats and other carnivores, adapted to
shear or puncture food. Carnassial teeth often
cause puncture wounds when a cat bites a human.
Culture—A laboratory procedure in which a sample from a wound, the blood or other body fluid is
taken from an infected person. The sample is placed
in conditions under which bacteria can grow. If
bacteria grow, identification tests are done to determine the bacteria species causing the infection.
Immunocompetence—An individual’s ability to
fight off infection.
Microorganisms—Microscopic organisms, such as
bacteria, viruses, algae and fungi.
Pasteurellosis—A bacterial infection caused by
Pasteurella multocida. Pasteurellosis is characterized by inflammation around the wound site and
may be accompanied by bacteria in the bloodstream and infection in tissues and organs.
This snake breeder shows the scar from his surgery after he
was bitten by a venomous West African Gabon viper. His arm
was cut open in order to relieve swelling from the snake bite
in his middle finger. (Photograph by Joe Crocetta, AP/Wide
World Photo. Reproduced by permission.)

(sharks, rays, eels, etc.) require immediate medical
attention as these bites may contain disease organisms
unique to the ocean environment as well as causing
severe loss of blood.
The bacterial species most commonly found
in bite wounds include Pasteurella multocida,
Staphylococcus aureus, Pseudomonas sp, and
Streptococcus sp. P. multocida, the root cause of pasteurellosis, is especially prominent in cat bite infections. Other infectious diseases from animal bites
include cat-scratch disease, tetanus and rabies.
Doctors are increasingly aware of the importance
of checking animal bite wounds for anaerobic organisms, which are microbes that can live and multiply in
the absence of air or oxygen. A study published in 2003
reported that about two-thirds of animal bite wounds
contain anaerobes. These organisms can produce such
GALE ENCYCLOPEDIA OF MEDICINE

Pathogen—Any disease-producing microorganism.
Postexposure prophylaxis (PEP)—Any treatment
given after exposure to a disease to try to prevent
the disease from occurring. In the case of rabies, PEP
involves a series of vaccines given to an individual
who has been bitten by an unknown animal or one
that is potentially infected with the rabies virus.
Tenosynovitis—Inflammation of the sheath of tissue that surrounds a tendon. Tenosynovitis is a
common complication of animal bites containing
anaerobic bacteria.
Zoonosis (plural, zoonoses)—Any disease of animals that can be transmitted to humans. Rabies is
an example of a zoonosis.

complications as septic arthritis, tenosynovitis, meningitis, and infections of the lymphatic system.
With regard to the most common types of domestic pets, it is useful to note that biting and other
aggressive behavior has different causes in dogs and
cats. To some extent these differences are rooted in
219

Animal bite infections

KEY TERMS

Animal bite infections

divergent evolutionary pathways, but they have also
been influenced by human interference through selective breeding. Dogs were first domesticated by humans
as early as 10,000 B.C. for hunting and as guard or
attack dogs. Many species travel in packs or groups
in the wild, and many human fatalities resulting from
dog bites involve a large group of dogs attacking one
or two persons. In addition, dogs typically relate to
humans according to a hierarchical model of dominance and submission, and many of the techniques of
dog training are intended to teach the dog to respect
human authority. Certain breeds of dogs are much
more likely to attack humans than others; those most
often involved in fatal attacks are pit bulls, Rottweilers,
German shepherds, huskies, and mastiffs. According to
the Centers for Disease Control (CDC), there are
between 15 and 20 fatal dog attacks on humans in the
United States each year. There are several assessment
or evaluation scales that veterinarians or animal trainers can use to score individual or mixed-breed dogs
for dominant or aggressive behavior.
Unlike dogs, cats were not domesticated until
about 3000 B.C., and were important to ancient civilizations as rodent catchers and household companions
rather than as protectors or hunters of wild game.
Biologists classify cats as solitary predators rather
than as pack or herd animals; as a result, cats do not
relate to humans as authority figures in the same way
that dogs do, and they do not form groups that attack
humans when threatened or provoked. In addition,
domestic cats have been selectively bred for appearance rather than for fierceness or aggression. Most cat
bites are the result of fear on the cat’s part (as when
being placed in a carrier for a trip to the vet) or a
phenomenon known as petting-induced aggression.
Petting-induced aggression is a behavior in which a
cat that has been apparently enjoying contact with a
human suddenly turns on the human and bites. This
behavior appears to be more common in cats that had
no contact with humans during their first seven weeks
of life. In other cats, this type of aggression appears to
be related to a hypersensitive nervous system; petting
or cuddling that was pleasurable to the cat for a few
seconds or minutes becomes irritating, and the cat
bites as a way of indicating that it has had enough.
In older cats, petting-induced aggression is often a sign
that the cat feels pain from touching or pressure on
arthritic joints in its neck or back.

Causes and symptoms
The most common sign of infection from an animal bite is inflammation. The skin around the wound
is red and feels warm, and the wound may exude pus.
220

Nearby lymph glands may be swollen. Complications
can arise if the infection is not treated and spreads into
deeper structures or into the bloodstream. If the bite is
deep or occurs on the hand or at a joint, complications
are more likely.
Live disease-causing bacteria within the bloodstream and tissues cause complications far from the
wound site. Such complications include meningitis,
brain abscesses, pneumonia and lung abscesses, and
heart infections, among others. These complications
can be fatal. Deep bites or bites near joints can damage
joints and bones, causing inflammation of the bone
and bone marrow or septic arthritis.
Cat-scratch disease is caused by Bartonella
henselae, a bacterium that is carried in cat saliva;
infection may be transmitted by a bite or scratch.
Approximately 22,000 cases are reported each year in
the United States; worldwide, nine out of every
100,000 individuals become infected. More than 80%
of reported cases occur in persons under the age of 21.
The disease is not normally severe in individuals with
healthy immune systems. Symptoms may become serious, however, in immunocompromised individuals,
such as those with acquired immune deficiency
syndrome (AIDS) or those undergoing chemotherapy.
Common symptoms include an inflamed sore in the
area of the bite or scratch, swollen lymph nodes, fever,
fatigue, and rash.
Rabies is caused by a virus that is transmitted
through the bite of an animal that is already
infected. It is classified as a zoonosis, which is a
term that refers to any disease of animals that can
be transmitted to humans. More than 90% of animal
rabies cases occur in such wild animals as skunks,
bats, and raccoons, with such domestic animals as
dogs and cats accounting for fewer than 10% of
cases. The World Health Organization (WHO) estimates that between 35,000 and 50,000 individuals
worldwide die each year as a result of rabies. The
highest incidence of rabies occurs in Asia where, in
1997, over 33,000 deaths were noted, most occurring
in India. Rabies is nowadays rare in the United
States, as a result of good animal control practices.
Onset is delayed, usually weeks to months after the
person has been bitten. Early symptoms of rabies
include fever, headache, and flu-like symptoms.
These progress to anxiety, hallucinations, muscle
spasms, partial paralysis, fear of water (hydrophobia), and other neurological symptoms as the virus
spreads to the central nervous system. Medical treatment must be sought soon after exposure because
death invariably follows once the infection becomes
established.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
A medical examination involves taking the history
of the injury and assessing the wound type and
damage. Tetanus immunization and general health
status are checked. An x ray may be ordered to assess
bone damage and to check for foreign objects in the
wound. Wound cultures are done for infected bites if
the victim is at high risk for complications or if the
infection does not respond to treatment. Evaluation of
possible exposure to rabies is also important. A biting
animal suspected of having rabies is usually apprehended, tested, and observed for a period of time for
evidence of pre-existing infection.

Treatment
Treatment depends on the wound type, its site,
and risk factors for infection. All wounds are
cleaned and disinfected as thoroughly as possible.
Bites to the head and face usually receive sutures, as
do severe lacerations elsewhere. Puncture wounds
are left open. If abscess formation occurs, the physician may perform an incision so as to drain the
abscess.
If infection occurs, antibiotics are prescribed.
Antibiotics may also be used for infection prevention. Since a single bite wound may contain many
different types of bacteria, no single antibiotic is
always effective. Commonly prescribed antibiotics
are penicillin or a combination of amoxicillin and
clavulanate potassium. Aztreonam has been
reported to be effective in treating infections caused
by P. multocida.
Because rabies is caused by a virus, antibiotics
are not effective. In addition, as of 2003, there is no
known cure for the disease once symptoms become
apparent. It is therefore recommended that individuals with a high risk of contracting the disease
(veterinarians, animal handlers, some laboratory
workers) receive preexposure vaccination. Individuals
bitten by an unknown or potentially rapid animal
should receive postexposure vaccination, also called
postexposure prophylaxis (PEP). The PEP regimen
consists of one dose of vaccine given at the initial visit
as well as one dose of human immune globulin.
Additional doses of vaccine are given on days 3, 7, 14,
and 28.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Once a bacterial infection is halted, the bite victim
usually recovers fully. There is no known cure for
rabies once symptoms become evident and death is
almost certain. WHO reports that 114 rabies deaths
occurred in the Americas in 1997, with only four
deaths occurring that year in the United States, thus
emphasizing the importance of good animal control
practice and postexposure prophylaxis.

Prevention
Preventing bites obviously prevents subsequent
infections. With regard to domestic pets, parents
should inform themselves about the aggression level
and other characteristics of a particular breed before
bringing a purebred pet dog into the family, and
consider having a specific dog evaluated by a veterinarian or animal behaviorist before adopting it. In
addition, parents should make sure that the dog has
been neutered or spayed, since intact dogs of either
sex are more likely to bite than those that have been
altered. Cat bites can often be prevented by learning
about a cat’s body language and recognizing the signs
of petting-induced aggression. These include dilating
pupils, a low growl, stiffening of the body, twitching
of the tail, and flattening the ears backward against
the head.
Children under 12 years of age are at a higher risk
for bites due to their small size and their inexperience
with animals; therefore, they should be supervised
with animals and taught to act appropriately around
them. In particular, children should be taught not to
tease a dog by pulling its fur or tail; to leave a dog
alone while it is eating; and to avoid running or
screaming in the presence of a dog, as the animal is
more likely to chase a moving object. Direct eye contact with a threatening dog should be avoided, as the
dog may interpret that as aggression. It is best to
stand still if at all possible, with feet together and
arms against the chest; most dogs will lose interest
in an object that is not moving, and will eventually go
away.
A wild animal that is unusually aggressive or
behaving strangely (e.g. a raccoon or bat that is active
during the daytime or is physically uncoordinated)
should be avoided and reported to the local animal
control authorities; it may be infected with the rabies
virus. Wild animals should not be taken in as pets, and
garbage or pet food that might attract wild animals
should not be left outside the home or camp site.
People should also avoid trying to break up fights
between animals and should as a rule approach
221

Animal bite infections

Most deaths from rabies in the United States
result from bat bites; the most recent victim was a
66-year-old man in California who died in September
2003 after failing to report a bat bite.

Ankylosing spondylitis

unknown cats and dogs very cautiously, especially on
their territory. Finally, animals should not be trained
to fight.
Domestic pets should be vaccinated against
rabies; people should consult a veterinarian for
advice about the frequency of booster vaccinations
for the area in which they live. In addition, people
who are traveling to countries where rabies is endemic should consider vaccination before leaving the
United States.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Central Nervous System Viral Diseases: Rabies
(Hydrophobia).’’ Section 13, Chapter 162 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 1999.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Infections of Bones and Joints.’’ Section 5, Chapter 54
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 1999.
Dodman, Nicholas H., DVM. If Only They Could Speak:
Stories About Pets and Their People. New York and
London: W. W. Norton and Company, 2002. Contains
several useful appendices about aggression in various
dog breeds and a sample assessment form for evaluating
a dog’s potential for biting.
Garvey, Michael S., DVM, Ann E. Hohenhaus, DVM,
Katherine A. Houpt, VMD, PhD, et al. The
Veterinarians’ Guide to Your Cat’s Symptoms. New
York: Villard, 1999.
PERIODICALS

Brook, I. ‘‘Microbiology and Management of Human and
Animal Bite Wound Infections.’’ Primary Care 30
(March 2003): 25–39.
Fooks, A. R., N. Johnson, S. M. Brookes, et al. ‘‘Risk
Factors Associated with Travel to Rabies Endemic
Countries.’’ Journal of Applied Microbiology 94,
Supplement (2003): 31S–36S.
Garcia Triana, M., M. A. Fernandez Echevarria, R. L.
Alvaro, et al. ‘‘Pasteurella multocida Tenosynovitis of
the Hand: Sonographic Findings.’’ Journal of Clinical
Ultrasound 31 (March-April 2003): 159–162.
‘‘Human Death Associated with Bat Rabies—California,
2003.’’ Morbidity and Mortality Weekly Report 53
(January 23, 2004): 33–35.
Le Moal, G., C. Landron, G. Grollier, et al. ‘‘Meningitis Due
to Capnocytophaga canimorsus After Receipt of a Dog
Bite: Case Report and Review of the Literature.’’ Clinical
Infectious Diseases 36 (February 1, 2003): 42–46.
Messenger, S. L., J. S. Smith, L. A. Orciari, et al. ‘‘Emerging
Pattern of Rabies Deaths and Increased Viral
Infectivity.’’ Emerging Infectious Diseases 9 (February
2003): 151–154.
222

Perkins, R. A., and S. S. Morgan. ‘‘Poisoning,
Envenomation, and Trauma from Marine Creatures.’’
American Family Physician 69 (February 15, 2004):
885–890.
Sacks, Jeffrey J., MD, MPH, Leslie Sinclair, DVM, Julie
Gilchrist, MD, et al. ‘‘Special Report: Breeds of Dogs
Involved in Fatal Human Attacks in the United States
Between 1979 and 1998.’’ Journal of the American
Veterinary Medical Association 217 (September 15,
2000): 836–840.
Weiss, R. A. ‘‘Cross-Species Infections.’’ Current Topics in
Microbiology and Immunology 278 (2003): 47–71.
Winner, J. S., C. A. Gentry, L. J. Machado, and P. Cornea.
‘‘Aztreonam Treatment of Pasteurella multocida
Cellulitis and Bacteremia.’’ Annals of Pharmacotherapy
37 (March 2003): 392–394.
ORGANIZATIONS

American Academy of Emergency Medicine (AAEM). 555
East Wells Street, Suite 1100, Milwaukee, WI 53202.
(800) 884-2236. Fax: (414) 276-3349. <http://
www.aaem.org>.
American Veterinary Medical Association (AVMA). 1931
North Meacham Road, Suite 100, Schaumburg, IL
60173-4360. <http://www.avma.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
OTHER

National Association of State Public Health Veterinarians,
Inc. ‘‘Compendium of Animal Rabies Prevention and
Control, 2003.’’ Morbidity and Mortality Weekly
Report Recommendations and Reports 52 (March 21,
2003) (RR-5): 1–6.
‘‘Rabies Situation and Trends.’’ Paris: World Health
Organization. 2001. <http://www.who.int/emc/
diseases/zoo/rabies.html>.

Julia Barrett
Rebecca J. Frey, PhD

I Ankylosing spondylitis
Definition
Ankylosing spondylitis (AS) refers to inflammation of the joints in the spine. AS is also known as
rheumatoid spondylitis or Marie-Strümpell disease
(among other names).

Description
A form of arthritis, AS is characterized by chronic
inflammation, causing pain and stiffness of the back,
GALE ENCYCLOPEDIA OF MEDICINE

Ankylosing—When bones of a joint are fused, stiff,
or rigid.
HLA-B27—An antigen or protein marker on cells
that may indicate ankylosing spondylitis.
Immune suppressing—Anything that reduces the
activity of the immune system.
Inflammation—A reaction of tissues to disease or
injury, often associated with pain and swelling.
Spondylitis—An inflammation of the spine.

Doctors usually diagnose the disease simply by
the patient’s report of pain and stiffness. Doctors
also review spinal and pelvic x rays since involvement
of the hip and pelvic joints is common and may be the
first abnormality seen on the x ray. The doctor may
also order a blood test to determine the presence of
HLA-B27 antigen. When a diagnosis is made, patients
may be referred to a rheumatologist, a doctor who
specializes in treating arthritis. Patients may also be
referred to an orthopedic surgeon, a doctor who can
surgically correct joint or bone disorders.

Treatment
progressing to the chest and neck. Eventually, the
whole back may become curved and inflexible if the
bones fuse (this is known as ‘‘bamboo spine’’). AS is a
systemic disorder that may involve multiple organs,
such as the:


eye (causing an inflammation of the iris, or iritis)



heart (causing aortic valve disease)



lungs



skin (causing a scaly skin condition, or psoriasis)



gastrointestinal tract (causing inflammation within
the small intestine, called ileitis, or inflammation of
the large intestine, called colitis)

Less than 1% of the population has AS; however,
20% of AS sufferers have a relative with the disorder.

Causes and symptoms
Genetics play an important role in the disease, but
the cause of AS is still unknown. More than 90% of
patients have a gene called HLA-B27, but only
10-15% of those who inherit the gene develop the
disease. Symptoms of AS include:


low back and hip pain and stiffness



difficulty expanding the chest



pain in the neck, shoulders, knees, and ankles



low-grade fever



fatigue



weight loss

AS is seen most commonly in males 30 years old
and older. Initial symptoms are uncommon after
the age of 30, although the diagnosis may not be
established until after that age. The incidence of AS
in Afro-Americans is about 25% of the incidence in
Caucasians.
GALE ENCYCLOPEDIA OF MEDICINE

Physical therapists prescribe exercises to prevent a
stooped posture and breathing problems when
the spine starts to fuse and ribs are affected. Back
braces may be used to prevent continued deformity
of the spine and ribs. Only in severe cases of deformity
is surgery performed to straighten and realign the
spine, or to replace knee, shoulder, or hip joints.

Alternative treatment
To reduce inflammation various herbal remedies,
including white willow (Salix alba), yarrow (Achillea
millefolium), and lobelia (Lobelia inflata), may be
helpful. Acupuncture, performed by a trained professional, has helped some patients manage their pain.
Homeopathic practitioners may prescribe such
remedies as Bryonia and Rhus toxicodendron for
pain relief.

Prognosis
There is no cure for AS, and the course of the
disease is unpredictable. Generally, AS progresses for
about 10 years and then its progression levels off.
Most patients can lead normal lives with treatment
to control symptoms.

Prevention
There is no known way to prevent AS.
Resources
ORGANIZATIONS

Arthritis Foundation.1300 W. Peachtree St., Atlanta, GA
30309. (800) 283-7800. <http://www.arthritis.org>.
National Institute of Arthritis and Musculoskeletal and Skin
Diseases Information Clearinghouse. 1 AMS Circle,
Bethesda, MD 29892-3675. (301) 495-4484.
223

Ankylosing spondylitis

Diagnosis

KEY TERMS

Anorexia nervosa

Spondylitis Association of America. P.O. Box 5872,
Sherman Oaks, CA 91413. (800) 777-8189.
OTHER

Matsen III, Frederick, ed. ‘‘Ankylosing Spondylitis.’’
University of Washington Orthopaedics and Sports
Medicine. <http://www.orthop.washington.edu/
arthritis/types/ankylosingspondylitis>.

Jeanine Barone, Physiologist

Anorectal abscess see Anorectal disorders

I Anorectal disorders
Definition
Anorectal disorders are a group of medical disorders that occur at the junction of the anal canal and the
rectum.

Description
The anal canal, also called the anus, is the opening
at the bottom end of the digestive tract and is a combination of external skin and tissue from the digestive
tract. It has many sensory nerves and is sensitive to
pain. The rectum is the last section of the digestive
tract and has a mucus layer as its inside surface. It
has very few sensory nerves and is, therefore, relatively
insensitive to pain. The anal canal has a ring of muscle,
called the anal sphincter, which keeps the anus closed.
There are a number of different anorectal disorders.

Causes and symptoms
An anal fissure is a tear in the lining of the anus
that is usually caused by a hard bowel movement.
Fissures are painful and bleed when the tissue is
stressed during bowel movements.
Anorectal abscesses are characterized by pusforming infections in the anorectal region. Painful
abscesses form under the skin.
An anorectal fistula is an abnormal opening or
channel from the anorectal area to another part of
the body. Typically, the channel leads to pockets of
skin near the anus. When seen in infants, anorectal
fistulas are considered birth defects. These are seen
more frequently in boys than in girls. Fistulas are
also seen more frequently in people who have other
diseases, including Crohn’s disease, tuberculosis,
cancer, and diverticulitis. Anorectal fistulas also
224

occur following anorectal abscesses or other injury
to the anal area. Fistulas are usually painful and
discharge pus.

Diagnosis
Diagnosis is made by visual inspection of the skin
around the anus. Also, the doctor may probe the
rectum with a gloved finger. An anoscope is a short
instrument that allows the physician to view the inside
of the anus. A proctoscope is a longer, rigid viewing
tube of approximately six to ten inches in length,
which may be used to look for anorectal disorders.
A sigmoidoscope is a longer, flexible tube, that
allows the physician to view up to about two feet of
the inside of the large intestine. Tissue samples and
material for microbial culture may be obtained during
the examination.

Treatment
Treatment usually isn’t required for hemorrhoids.
Most hemorrhoids will heal if the patient takes stool
softeners to relieve the constipation. Enlarged blood
vessels can be eliminated by surgery if they are considered
a severe problem. In the case of fissures, treatment
involves stool softeners that eliminate stress on the
fissure during bowel movements, which allows the fissure
to heal. If the fissure doesn’t heal, surgery is required.
Treatment for anorectal abscesses consists of cutting the
abscess and draining the pus. Fistulas are treated by
surgery.The usual treatment for proctitis is antibiotics.
Resources
BOOKS

Berkow, Robert, editor. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 1997.

John T. Lohr, PhD

Anorectal fistula see Anorectal disorders

I Anorexia nervosa
Definition
Anorexia nervosa is an eating disorder characterized by unrealistic fear of weight gain, self-starvation,
and conspicuous distortion of body image. The name
comes from two Latin words that mean nervous
inability to eat. In females who have begun to
GALE ENCYCLOPEDIA OF MEDICINE

Description
Anorexia nervosa was not officially classified as a
psychiatric disorder until the third edition of DSM in
1980. It is, however, a growing problem among adolescent females. Its incidence in the United States has
doubled since 1970. The rise in the number of reported
cases reflects a genuine increase in the number of
persons affected by the disorder, and not simply earlier
or more accurate diagnosis. Estimates of the incidence
of anorexia range between 0.5–1% of caucasian female
adolescents. Over 90% of patients diagnosed with the
disorder as of 1998 are female. It was originally thought
that only 5% of anorexics are male, but that estimate is
being revised upward. The peak age range for onset of
the disorder is 14-18 years, although there are patients
who develop anorexia as late as their 40s. In the 1970s
and 1980s, anorexia was regarded as a disorder of
upper- and middle-class women, but that generalization
is also changing. More recent studies indicate that
anorexia is increasingly common among women of all
races and social classes in the United States.
Anorexia nervosa is a serious public health
problem not only because of its rising incidence, but
also because it has one of the highest mortality rates
of any psychiatric disorder. Moreover, the disorder
may cause serious long-term health complications,
including congestive heart failure, sudden death,
growth retardation, dental problems, constipation,
stomach rupture, swelling of the salivary glands, anemia and other abnormalities of the blood, loss of
kidney function, and osteoporosis.

Causes and symptoms
Anorexia is a disorder that results from the interaction of cultural and interpersonal as well as biological factors. While the precise cause of the disease is not
known, it has been linked to the following:
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Amenorrhea—Absence of the menses in a female
who has begun to have menstrual periods.
Binge eating—A pattern of eating marked by episodes of rapid consumption of large amounts of
food; usually food that is high in calories.
Body dysmorphic disorder—A psychiatric disorder
marked by preoccupation with an imagined physical defect.
Hyperalimentation—A method of refeeding anorexics by infusing liquid nutrients and electrolytes
directly into central veins through a catheter.
Lanugo—A soft, downy body hair that develops on
the chest and arms of anorexic women.
Purging—The use of vomiting, diuretics, or laxatives
to clear the stomach and intestines after a binge.
Russell’s sign—Scraped or raw areas on the patient’s
knuckles, caused by self-induced vomiting.
Superior mesenteric artery syndrome—A condition in which a person vomits after meals due to
blockage of the blood supply to the intestine.

Social influences
The rising incidence of anorexia is thought to
reflect the present idealization of thinness as a badge
of upper-class status as well as of female beauty. In
addition, the increase in cases of anorexia includes
‘‘copycat’’ behavior, with some patients developing
the disorder from imitating other girls.
The onset of anorexia in adolescence is attributed
to a developmental crisis caused by girls’ changing
bodies coupled with society’s overemphasis on
women’s looks. The increasing influence of the mass
media in spreading and reinforcing gender stereotypes
has also been noted.
Occupational goals
The risk of developing anorexia is higher among
adolescents preparing for careers that require attention to weight and/or appearance. These high-risk
groups include dancers, fashion models, professional
athletes (including gymnasts, skaters, long-distance
runners, and jockeys), and actresses.
Genetic and biological influences
Women whose biological mothers or sisters have
the disorder appear to be at increased risk.
225

Anorexia nervosa

menstruate, anorexia nervosa is usually marked by
amenorrhea, or skipping at least three menstrual periods in a row. The fourth edition of the Diagnostic and
Statistical Manual of Mental Disorders, or DSM-IV
(1994), defines two subtypes of anorexia nervosa–a
restricting type, characterized by strict dieting and
exercise without binge eating; and a binge-eating/purging type, marked by episodes of compulsive eating
with or without self-induced vomiting and the use of
laxatives or enemas. DSM-IV defines a binge as a
time-limited (usually under two hours) episode of
compulsive eating in which the individual consumes
a significantly larger amount of food than most people
would eat in similar circumstances.

Anorexia nervosa

Psychological factors
A number of theories have been advanced to
explain the psychological aspects of the disorder. No
single explanation covers all cases. Anorexia nervosa
has been interpreted as:


A rejection of female sexual maturity. This rejection
is variously interpreted as a desire to remain a child,
or as a desire to resemble men as closely as possible.



A reaction to sexual abuse or assault.



A desire to appear as fragile and nonthreatening as
possible. This hypothesis reflects the idea that female
passivity and weakness are attractive to men.



Overemphasis on control, autonomy, and independence. Some anorexics come from achievementoriented families that stress physical fitness and
dieting. Many anorexics are perfectionistic and
‘‘driven’’ about schoolwork and other matters in
addition to weight control.



Evidence of family dysfunction. In some families, a
daughter’s eating disorder serves as a distraction
from marital discord or other family tensions.



Inability to interpret the body’s hunger signals accurately due to early experiences of inappropriate
feeding.
Male anorexics

Although anorexia nervosa is still considered a
disorder that largely affects women, its incidence in
the male population is rising. Less is known about the
causes of anorexia in males, but some risk factors are
the same as for females. These include certain occupational goals and increasing media emphasis on external appearance in men. Moreover, homosexual males
are under pressure to conform to an ideal body weight
that is about 20 pounds lighter than the standard
‘‘attractive’’ weight for heterosexual males.

Diagnosis
Diagnosis of anorexia nervosa is complicated by a
number of factors. One is that the disorder varies
somewhat in severity from patient to patient. A second
factor is denial, which is regarded as an early sign of
the disorder. Most anorexics deny that they are ill and
are usually brought to treatment by a family member.
Most anorexics are diagnosed by pediatricians or
family practitioners. Anorexics develop emaciated
bodies, dry or yellowish skin, and abnormally low
blood pressure. There is usually a history of amenorrhea (failure to menstruate) in females, and sometimes
226

of abdominal pain, constipation, or lack of energy.
The patient may feel chilly or have developed lanugo,
a growth of downy body hair. If the patient has been
vomiting, she may have eroded tooth enamel or
Russell’s sign (scars on the back of the hand). The
second step in diagnosis is measurement of the
patient’s weight loss. DSM-IV specifies a weight loss
leading to a body weight 15% below normal, with
some allowance for body build and weight history.
The doctor will need to rule out other physical
conditions that can cause weight loss or vomiting
after eating, including metabolic disorders, brain
tumors (especially hypothalamus and pituitary gland
lesions), diseases of the digestive tract, and a condition
called superior mesenteric artery syndrome. Persons
with this condition sometimes vomit after meals
because the blood supply to the intestine is blocked.
The doctor will usually order blood tests, an electrocardiogram, urinalysis, and bone densitometry (bone
density test) in order to exclude other diseases and to
assess the patient’s nutritional status.
The doctor will also need to distinguish between
anorexia and other psychiatric disorders, including
depression, schizophrenia, social phobia, obsessivecompulsive disorder, and body dysmorphic disorder.
Two diagnostic tests that are often used are the
Eating Attitudes Test (EAT) and the Eating Disorder
Inventory (EDI).

Treatment
Treatment of anorexia nervosa includes both
short- and long-term measures, and requires assessment
by dietitians and psychiatrists as well as medical specialists. Therapy is often complicated by the patient’s
resistance or failure to carry out treatment plan.
Hospital treatment
Hospitalization is recommended for anorexics
with any of the following characteristics:


weight of 40% or more below normal; or weight loss
over a three-month period of more than 30 pounds



severely disturbed metabolism



severe binging and purging



signs of psychosis



severe depression or risk of suicide



family in crisis

Hospital treatment includes individual and group
therapy as well as refeeding and monitoring of the
patient’s physical condition. Treatment usually
GALE ENCYCLOPEDIA OF MEDICINE

Outpatient treatment
Anorexics who are not severely malnourished can
be treated by outpatient psychotherapy. The types of
treatment recommended are supportive rather than
insight-oriented, and include behavioral approaches
as well as individual or group therapy. Family therapy
is often recommended when the patient’s eating disorder is closely tied to family dysfunction. Self-help
groups are often useful in helping anorexics find social
support and encouragement. Psychotherapy with
anorexics is a slow and difficult process; about 50%
of patients continue to have serious psychiatric problems after their weight has stabilized.

ORGANIZATIONS

American Anorexia/Bulimia Association. 418 East 76th St.,
New York, NY 10021. (212) 734-1114.
National Institute of Mental Health Eating Disorders
Program. Building 10, Room 3S231. 9000 Rockville
Pike, Bethesda, MD 20892. (301) 496-1891.

Rebecca J. Frey, PhD

I Anoscopy
Definition
An anoscopy is an examination of the rectum in
which a small tube is inserted into the anus to screen,
diagnose, and evaluate problems of the anus and anal
canal.

Medications
Anorexics have been treated with a variety of
medications, including antidepressants, antianxiety
drugs, selective serotonin reuptake inhibitors, and
lithium carbonate. The effectiveness of medications
in treatment regimens is still debated. However, at
least one study of Prozac showed it helped the patient
maintain weight gained while in the hospital.

Purpose
This test may be ordered for the evaluation of
perianal or anal pain, hemorrhoids, rectal prolapse,
digital rectal examination that shows a mass, perianal
abscess and condyloma (a wart-like growth). An anascopy may be performed to check for abnormal openings between the anus and the skin, or anal fissures.
The test is also used to diagnose rectal cancer.

Prognosis
Figures for long-term recovery vary from study to
study, but the most reliable estimates are that 40-60%
of anorexics will make a good physical and social
recovery, and 75% will gain weight. The long-term
mortality rate for anorexia is estimated at around
10%, although some studies give a lower figure of
3-4%. The most frequent causes of death associated
with anorexia are starvation, electrolyte imbalance,
heart failure, and suicide.

Prevention
Short of major long-term changes in the larger
society, the best strategy for prevention of anorexia
is the cultivation of healthy attitudes toward food,
weight control, and beauty (or body image) within
families.
Resources
BOOKS

Baron, Robert B. ‘‘Nutrition.’’ In Current Medical Diagnosis
and Treatment, 1998, edited by Stephen McPhee, et al.,
37th ed. Stamford: Appleton & Lange, 1997.
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Anoscopy should not be performed on patients
with acute cardiovascular problems due to the vasovagal reaction it may cause. This test is also not recommended for patients with acute abdominal problems
and those with a constricted or narrowed anal canal.

Description
Anoscopy views the anus and anal canal by using
an anoscope. An anoscope is a plastic, tube-shaped
speculum that is a smaller version of a sigmoidscope.
Before the anoscope is used, the doctor completes a
digital rectal examination with a lubricated, gloved
index finger. The anoscope is then lubricated and
gently inserted a few inches into the rectum. This
procedure enlarges the rectum to allow the doctor to
view the entire anal canal with a light. If any suspicious
areas are noticed, a piece of tissue can be biopsied.
During the anoscopy procedure there may be a
feeling of pressure or the need to go to the bathroom.
If a biopsy is taken, the patient may feel a slight pinch.
227

Anoscopy

requires two to four months in the hospital. In extreme
cases, hospitalized patients may be force-fed through a
tube inserted in the nose (nasogastric tube) or by overfeeding (hyperalimentation techniques).

Anosmia

Resources

KEY TERMS
Anal fissure—An ulcer on the margin of the anus.
Digital rectal examination—An examination
where a gloved, lubricated index finger is inserted
into the rectum to check for any abnormalities.
Polyps—A tumor with a small flap that attaches
itself to the wall of various vascular organs such as
the nose, uterus and rectum. Polyps bleed easily,
and if they are suspected to be cancerous they
should be surgically removed.
Vasovagal reaction—Regarding the action of
stimuli from the vagus nerve on blood vessels.

BOOKS

Altman, Roberta, and Michael J. Sarg. ‘‘Anoscopy.’’ The
Cancer Dictionary. Checkmark Books, 2000, p. 18.
PERIODICALS

Colyar, Margaret. ‘‘Anascopy Basics.’’ The Nurse
Practitioner (October 2000): 91.
OTHER

Discovery Health. ‘‘Medical Tests: Anoscopy.’’ May 5,
2001. <http://health.discover.com/diseasesandcond/
encyclopedia/1038.html>.
Lycos Health with WebMD. ‘‘Anoscopy.’’ May 5, 2001.
<http://webmd.lycos.com/content/asset/
adam_test_anoscopy>.

Beth A. Kapes
The procedure is performed on an out-patient basis,
and takes approximately an hour to complete.

Preparation
The patient will be instructed to clear their rectum
of stool before the procedure. This may be done by
taking a laxative, enema, or other preparation that
may help with the evacuation.

Aftercare
If a biopsy is needed during an anoscopy, there may
be slight anal bleeding for less than two days following
the procedure. The patient may be instructed to sit in a
bathtub of warm water for 10 to 15 minutes, three
times a day, to help decrease the pain and swelling.

Risks
A simple anoscopy procedure offers minimal
risks. There is a limited risk of bleeding and mild
pain is a biopsy is performed.

Normal results
Normal values to look for during an anoscopy
include an anal canal that appears healthy in size,
color, and shape. The test also looks for no evidence of
bleeding, polyps, hemorrhoids or other abnormalities.

Abnormal results
While an anoscopy is typically performed to
determine is hemorrhoids are present, other abnormal
finding could include polyps, abscesses, inflammation,
fissures, colorectal polyps, or cancer.
228

I Anosmia
Definition
The term anosmia means lack of the sense of
smell. It may also refer to a decreased sense of smell.
Ageusia, a companion word, refers to a lack of taste
sensation. Patients who actually have anosmia may
complain wrongly of ageusia, although they retain
the ability to distinguish salt, sweet, sour, and bitter–
humans’ only taste sensations.

Description
Of the five senses, smell ranks fourth in importance
for humans, although it is much more pronounced in
other animals. Bloodhounds, for example, can smell an
odor a thousand times weaker than humans. Taste,
considered the fifth sense, is mostly the smell of food
in the mouth. The sense of smell originates from the
first cranial nerves (the olfactory nerves), which sit at
the base of the brain’s frontal lobes, right behind the
eyes and above the nose. Inhaled airborne chemicals
stimulate these nerves.
There are other aberrations of smell beside a
decrease. Smells can be distorted, intensified, or hallucinated. These changes usually indicate a malfunction
of the brain.

Causes and symptoms
The most common cause of anosmia is nasal
occlusion caused by rhinitis (inflammation of the
GALE ENCYCLOPEDIA OF MEDICINE

Allergen—Any substance that irritates only those
who are sensitive (allergic) to it.
Corticosteroids—Cortisone, prednisone, and
related drugs that reduce inflammation.
Rhinitis—Inflammation and swelling of the nasal
membranes.
Nasal polyps—Drop-shaped overgrowths of the
nasal membranes.

nasal membranes). If no air gets to the olfactory
nerves, smell will not happen. In turn, rhinitis and
nasal polyps (growths on nasal membranes) are caused
by irritants such as allergens, infections, cigarette
smoke, and other air pollutants. Tumors such as
nasal polyps can also block the nasal passages and
the olfactory nerves and cause anosmia. Head injury
or, rarely, certain viral infections can damage or
destroy the olfactory nerves.

first step to healing. Nasal steams with essential oils
offer relief of the blockage and tonification of the
membranes. Blockages can sometimes be resolved
through naso-specific therapy–a way of realigning
the nasal cavities. Polyp blockage can be addressed
through botanical medicine treatment as well as
hydrotherapy. Olfactory nerve damage may not be
regenerable. Some olfactory aberrations, like intensified sense of smell, can be resolved using homeopathic
medicine.

Prognosis
If nasal inflammation is the cause of anosmia, the
chances of recovery are excellent. However, if nerve
damage is the cause of the problem, the recovery of
smell is much more difficult.
Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Diagnosis
It is difficult to measure a loss of smell, and no one
complains of loss of smell in just one nostril. So a
physician usually begins by testing each nostril separately with a common, non-irritating odor such as
perfume, lemon, vanilla, or coffee. Polyps and rhinitis
are obvious causal agents a physician looks for.
Imaging studies of the head may be necessary in
order to detect brain injury, sinus infection, or tumor.

Treatment
Cessation of smoking is the first step. Many smokers who quit discover new tastes so enthusiastically
that they immediately gain weight. Attention to reducing exposure to other nasal irritants and treatment of
respiratory allergies or chronic upper respiratory
infections will be beneficial. Corticosteroids are particularly helpful.

Alternative treatment
Finding and treating the cause of the loss of smell
is the first approach in naturopathic medicine. If rhinitis is the cause, treating acute rhinitis with herbal mast
cell stabilizers and herbal decongestants can offer some
relief as the body heals. If chronic rhinitis is present,
this is often related to an environmental irritant or to
food allergies. Removal of the causative factors is the
GALE ENCYCLOPEDIA OF MEDICINE

Anoxemia see Anoxia

I Anoxia
Definition
Anoxia is a condition characterized by an absence
of oxygen supply to an organ or a tissue.

Description
Anoxia results when oxygen is not being delivered
to a part of the body. If the condition does not involve
total oxygen deprivation, it is often called hypoxia,
although the two terms have been used interchangeably. A related condition, anoxemia, occurs when the
blood circulates but contains a below normal amount
of oxygen.
The five types of anoxia or hypoxia include
hypoxemic, anemic, affinity, stagnant, and histotoxic.
Hypoxemic anoxia happens when the oxygen pressure
outside the body is so low that the hemoglobin, the
chemical which carries oxygen in the red blood cells
(RBCs), is unable to become fully loaded with the gas.
This results in too little oxygen reaching the tissues
and can occur in suffocation when a person is at high
229

Anoxia

KEY TERMS

Anoxia

KEY TERMS
Amnesia—Loss of memory often traceable to brain
tissue damage.
Anoxemia—An extreme lack of oxygen in the blood.
Hemoglobin—A chemical found in red blood cells
that transports oxygen.
Myoclonus—Involuntary contractions of a muscle
or group of muscles.

altitude, where the pressure of oxygen in the air is
much less than at sea level.
Anemic anoxia results from a decrease in the
amount of hemoglobin or RBCs in the blood, which
reduces the ability to get oxygen to the tissues. Anemia
may result from lack of production of red blood cells
(iron deficiency), blood loss (hemorrhage), or shortened lifespan of red blood cells (autoimmune disease).
Affinity anoxia involves a defect in the chemistry
of the blood such that the hemoglobin can no longer
pick up as much oxygen from the air, even though the
quantities are normal, reducing how much is delivered
to the tissues.
Stagnant anoxia occurs when there is interference
with the blood flow, although the blood and its
oxygen-carrying abilities are normal. A common
cause of general stagnant anoxia is heart disease or
interference with the return of blood flow through the
veins. Examples of local stagnant anoxia include exposure to cold, diseases that restrict circulation to the
extremities, and ergot poisoning. When the tissue or
organ itself has a reduced ability to accept and use the
oxygen, it is called histotoxic anoxia. The classic example is cyanide poisoning, where the chemical inactivates a cellular enzyme necessary for the cell to use
oxygen. Thus, tissue exposed to cyanide cannot use the
oxygen even though it is in normal amounts in the
bloodstream. Histotoxic anoxia can also be caused
by exposure to narcotics, alcohol, formaldehyde, acetone, toluene, and certain anesthetic agents.

through mountain climbing or travel in an insufficiently
pressurized airplane. Anoxia, and the resultant brain
damage, is a particular problem with newborns during
difficult births.
No matter what the cause of anoxia, the symptoms are similar. In severe cases, the patient is often
confused and commonly stuperous or comatose (in a
state of unconsciousness). Depending on the severity
of the injury to the brain, the organ most sensitive to
reduced oxygen intake, this condition can persist for
hours, days, weeks, or even months or years. Seizures,
myoclonic jerks (involuntary muscle spasms or
twitches), and neck stiffness are some other symptoms
of the anoxic condition.
Symptoms of more localized or less complete oxygen deprivation (hypoxia) include increased breathing
rate, lightheadedness, dizziness, tingling or warm sensation, sweating, reduced field of vision, sleepiness, a
bluish tint to skin, particularly the fingertips and lips,
and behavior changes, often an inappropriate sense of
euphoria.

Diagnosis
Diagnosis of anoxia and hypoxia is commonly
made through the appearance of clinical symptoms.
However, suspected reduction in oxygen reaching the
tissues can be confirmed using laboratory tests. The
exact test that is performed is dependent on the suspected cause of the anoxia. One systemic measure of
tissue anoxia is the serum lactate (lactic acid) test.
When cells are forced to produce energy without oxygen, as would happen during anoxia, lactic acid is one
of the byproducts. Thus, an increase in lactic acid in
the blood would indicate that tissues were starved for
oxygen and are using non-oxygen pathways to produce energy. Normally, the blood contains less than
2mmol/L of lactic acid. However, some forms of
anoxia do not increase lactic acid concentrations in
the blood and some increases in lactic acid levels are
not associated with anoxia, so an elevated value for
this test is only suggestive of an anoxic or hypoxic
condition.

Treatment
Causes and symptoms
Anoxia and hypoxia can be caused by any number
of disease states of the blood, lungs, heart and circulation
including heart attack, severe asthma, or emphysema.
It can also result from smoke or carbon monoxide inhalation, improper exposure to anesthesia, poisoning,
strangulation, near-drowning, or high altitude exposure
230

The exact treatment for anoxia is dependent on
the cause of the reduced oxygen reaching the tissues.
However, immediate restoration of tissue oxygen
levels through supplementing the patient’s air supply
with 100% oxygen is a common first step. Secondary
steps often include support of the cardiovascular system through drugs or other treatment, treatment of
GALE ENCYCLOPEDIA OF MEDICINE

<http://www.ninds.nih.gov/health_and_medical/
disorders/anoxia_doc.htm>.

Michelle Johnson, MS, JD

Prognosis
A good prognosis is dependent on the ability to
treat the underlying cause of the low oxygen levels. If
cardiovascular and respiratory systems can be supported adequately, recovery from the injury to the
tissue is possible, although extent of injury to the
brain can be difficult to assess. The exact amount of
recovery varies with the amount of injury sustained,
where significant injury brings a poorer prognosis. As
recovery occurs, both psychological and neurological
abnormalities may appear, persist, and can improve.
Some problems seen after anoxia include mental confusion, personality changes, amnesia or other types of
memory loss, hallucinations, and persistent myoclonus
(involuntary contractions of the muscles).

Prevention
Hypoxemic anoxia can be avoided by utilizing
supplemental oxygen when in high altitudes and
being aware of the early symptoms of altitude sickness and reducing altitude once recognized. Iron supplements can avoid anemic hypoxia, although more
severe anemic states are usually caused by disease or
bleeding. Maintaining good cardiovascular health
through proper diet and exercise is a good first step
to avoiding the most common cause of stagnant
anoxia. Avoiding exposure to the toxic chemicals
that cause the condition can prevent histotoxic
anoxia.
Resources
PERIODICALS

Gutierrez, Guillermo. ‘‘Metabolic Assessement of Tissue
Oxygenation’’ Seminars in Respiratory and Critical
Care Medicine 20 (January 1999): 11–15.
ORGANIZATIONS

Brain Injury Association. 105 N. Alfred St. Alexandria, VA
22314. (800) 444-6443. <http://www.biausa.org>.
Phoenix Project/Head Injury Hotline. Box 84151, Seattle,
WA 98124. (206) 621-8558. <http://
www.headinjury.com>.
OTHER

Borron, Stephen W. ‘‘Lactic Acidosis.’’ eMedicine. February 7,
2001. [cited May 13, 2001]. <http://www.emedicine.com/
emerg/topic291.htm>.
NINDS Anoxia/Hypoxia Information Page. The National
Institute of Neurological Disorders and Stroke
(NINDS). January 22, 2001. [cited May 13, 2001].
GALE ENCYCLOPEDIA OF MEDICINE

I Antacids
Definition
Antacids are medicines that neutralize stomach acid.

Purpose
Antacids are used to relieve acid indigestion, upset
stomach, sour stomach, and heartburn. Additional
components of some formulations include dimethicone, to reduce gas pains (flatulence) and alginic
acid, which, in combination with antacids, may help
manage GERD (gastro-esophageal reflux disease).
Antacids should not be confused with gastric acid
inhibitors, such as the H-2 receptor blockers (cimetidine, ranitide and others) or the proton pump inhibitors
(lansoprazole, omeprazole and others). Although all
three classes of drugs act to reduce the levels of gastric
acid, their mechanisms are different, and this affects
the appropriate use of the drug. Antacids have a rapid
onset and short duration of action, and are most
appropriate for rapid relief of gastric discomfort for
a short period of time.
Antacids may be divided into two classes, those
that work by chemical neutralization of gastric acid,
most notably sodium bicarbonate; and those that act
by adsorption of the acid (non-absorbable antacids),
such as calcium and magnesium salts.
The chemical antacids show the most rapid onset
of action, but may cause ‘‘acid rebound,’’ a condition
in which the gastric acid returns in greater concentration after the drug effect has stopped. Also, since
these antacids may contain high concentrations of
sodium, they may be inappropriate in patients with
hypertension.
Calcium and magnesium salts act by adsorption
of the acid, and are less prone to the rebound effect,
but may have other significant disadvantages. These
antacids are particularly prone to drug interactions,
and patients taking other medications must often
avoid simultaneous administration of the medications. These antacids are more effective in liquid formulations than in tablet or capsule form, and so may
be inconvenient for routine dosing.
231

Antacids

lung disease, transfusions, or administration of anecdotes for poisoning, as appropriate.

Antacids

KEY TERMS
Acid indigestion—Indigestion that results from too
much acid in the stomach.
Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Heartburn—A burning sensation, usually in the
center of the chest, near the breastbone.
Indigestion—A feeling of discomfort or illness that
results from the inability to properly digest food.
Inflamed bowel—Irritation of the intestinal tract.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Pregnancy safety categories—A system for reporting the known safety issues of drugs for use during
pregnancy, The ratings range from A, proven safe
by well controlled studies, to X, proven harmful.

The non-absorbable antacids may have additional
uses beyond control of hyperacidity. Calcium salts
may be used as diet supplements in prevention of
osteoporosis. Aluminum carbonate is useful for binding phosphate, and has been effective in treatment and
control of hyperphosphatemia or for use with a low
phosphate diet to prevent formation of phosphate
urinary stones. This application is particularly valuable in patients with chronic renal failure. Antacids
with aluminum and magnesium hydroxides or aluminum hydroxide alone effectively prevent significant
stress ulcer bleeding in post-operative patients or
those with severe burns.

Recommended dosage
The dose depends on the type of antacid. Consult
specific references.
When using antacids in chewable tablet form,
chew the tablet well before swallowing. Drink a glass
of water after taking chewable aluminum hydroxide.
Lozenges should be allowed to dissolve completely in
the mouth. Liquid antacids should be shaken well
before using.

Precautions
Antacids should be avoided if any signs of appendicitis or inflamed bowel are present. These include
cramping, pain, and soreness in the lower abdomen,
bloating, and nausea and vomiting.
232

Antacids may affect the results of some medical
tests, such as those that measure how much acid
the stomach produces. Health care providers and
patients should keep this in mind when scheduling a
medical test.
Antacids that contain magnesium may cause diarrhea. Other types of antacids may cause constipation.
Avoid taking antacids containing sodium bicarbonate when the stomach is uncomfortably full from
eating or drinking.
Antacids should not be given to children under six
years of age.
Antacids that contain calcium or sodium bicarbonate may cause side effects, such as dizziness, nausea,
and vomiting, in people who consume large amounts
of calcium (from dairy products or calcium supplements). In some cases, this can lead to permanent
kidney damage. Before combining antacids with
extra calcium, check with a physician.
Some antacids contain large amounts of sodium,
particularly sodium bicarbonate (baking soda).
Anyone who is on a low-sodium diet should check
the list of ingredients or check with a physician or
pharmacist before taking an antacid product.
Excessive use of antacids may cause or increase
the severity or kidney problems. Calcium based antacids may lead to renal stone formation.
PREGNANCY. Antacids are not classified under
the pregnancy safety categories A, B, C, D and X.
Occasional use of antacids in small amounts during
pregnancy is considered safe. However, pregnant
women should check with their physicians before using
antacids or any other medicines. Pregnant women
who are consuming extra calcium should be aware
that using antacids that contain sodium bicarbonate or
calcium can lead to serious side effects.
BREASTFEEDING. Some antacids may pass into
breast milk. However, no evidence exists that the
ingestion of antacids through breast milk causes problems for nursing babies whose mothers use antacids
occasionally.

Side effects
Side effects are very rare when antacids are taken
as directed. They are more likely when the medicine is
taken in large doses or over a long time. Minor side
effects include a chalky taste, mild constipation or
diarrhea, thirst, stomach cramps, and whitish or
speckled stools. These symptoms do not need medical
GALE ENCYCLOPEDIA OF MEDICINE

Other uncommon side effects may occur. Anyone
who has unusual symptoms after taking antacids
should get in touch with his or her health care provider.

Interactions
Antacids have multiple drug interactions, usually
due to inhibition of absorption of other medications.
In rare cases, the absorbable antacids may alter the
pH of the stomach contents or urine sufficiently to
alter drug absoprtion or excretion. Consult specific
references.
Samuel D. Uretsky, PharmD

Antegrade pyelography see Intravenous
urography

I Antenatal testing
Definition
Antenatal testing includes any diagnostic procedures performed before the birth of a baby.

Purpose
These tests and exams are essential for protecting
the health of a pregnant woman and her developing
child.

KEY TERMS
Ultrasound — A device that records sound waves
as they bounce off a developing fetus to create an
image, which is projected onto a large computer
screen
Breech position—When a child is oriented feet
first in the mother’s uterus just before delivery.
Alpha fetoprotein screen — A test that measures
the level of alpha fetoprotein, a substance produced by a fetus with birth defects, in the mother’s
blood.
Amniocentesis— An invasive procedure that
allows physicians to check for birth defects by collecting a sample of fetal cells from inside the
amniotic sac.
GBS— Group B streptococci are a type of bacteria
that, if passed to a can cause inflammation of the
brain, spinal cord, blood or lungs. In some cases, it
can result in infant death

When a woman first learns she is pregnant, her
physician will run a series of routine urine and blood
tests to determine her blood type, check for anemia
and gestational diabetes, make sure she is immune to
rubella (German measles) and check for infectious
diseases like HIV, hepatitis, chlamydia or syphilis.
Physicians also usually do pelvic exam to screen for
cervical cancer and check the patient’s blood pressure.
As the pregnancy progresses, more tests will follow.
Ultrasound

Precautions
Some tests, such as amniocentisis, carry a small
risk of a miscarriage or other complications that could
harm the mother or baby.

Description
Women who become pregnant undergo a wide
variety of tests throughout the nine months before
delivery. In the early stages, physicians order blood
tests to screen for possible disorders or infections, such
as human immunodeficiency virus (HIV), which can
pass from the mother to the fetus. Later, the focus
shifts to checking on fetal well-being with a variety of
technological tools such as ultrasound scans.
Descriptions of the most common tests and procedures used during pregnancy are listed below.
GALE ENCYCLOPEDIA OF MEDICINE

Ultrasound is a device that records sound waves
as they bounce off the developing fetus to create an
image, which is projected onto a large computer
screen. Physicians order an ultrasound scan to listen
for a fetal heartbeat, determine a woman’s precise due
date and check for twins, among other uses. An ultrasound scan also is known as a sonogram. The procedure takes a few minutes, is painless and usually is
covered by health insurance.
The ultrasound technician will ask the pregnant
woman to remove her clothes and change into a gown.
The technician may rub some gel on the woman’s stomach, which helps the hand-held device pick up sound
waves better. In certain cases, the technician may insert
a plastic probe into the woman’s vaginal canal to get a
clearer picture of the fetus. Early in pregnancy, the
test may need to be done with a full bladder.
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Antenatal testing

attention unless they do not go away or they interfere
with normal activities.

Antenatal testing

Unlike x rays, ultrasound is safe to use during
pregnancy. It does not cause any known side-effects
that would harm the mother or baby.

In about one out of every 1,000 cases, amniocentesis causes a needle to puncture the uterine wall,
which could result in miscarriage.

Pregnant women usually will have their first ultrasound anytime between 8 and 12 weeks of gestation. In
normal cases, the technician is able to identify a fetal
heartbeat, which appears as a flashing light on the
screen. Closer to the due date, physicians use ultrasound to make sure the fetus is in the correct position
to exit the birth canal head first.

In most cases, couples find out their baby does not
have a birth defect.

Sometimes an ultrasound will show that a fetus
has stopped growing, or a gestational sac has formed
without a fetus, and a miscarriage has occurred. Later
in pregnancy, it also may show that the child is in a
breech position, oriented feet first, which can cause a
difficult labor.
Tests for birth defects

If the results come back positive for Down’s
Syndrome or other serious conditions, the couple
must decide if they want to end the pregnancy.
Others use the knowledge to plan and prepare any
special care needed for their future child.
Group B Strep
This test is for Group B streptococci (GBS)
infection.
By testing for GBS, physicians can determine if
a woman is at risk of passing this infection along to
her child.

Most obstetricians offer parents a variety of ways
to find out if their developing child might have birth
defects such as spina bifida and Down Syndrome. An
alpha fetoprotein screen can be done through a simple
blood test in the doctor’s office between the 16th and
18th week of gestation. It tells the odds that their child
will have a severe congenital anomaly. The test works
by measuring the level of alpha fetoprotein, a substance produced by a fetus with birth defects. Low
levels of alpha fetoprotein in the mother’s blood may
indicate Down’s Syndrome. In that case, the next step
for most couples is amniocentesis because the alpha
fetoprotein test can give false-positive results.
Amniocentesis is a more accurate test, but it also has
higher risks of complications.

GBS is a type of bacteria commonly found in the
vagina and rectum. Unlike regular strep throat, GBS
can be present in a person’s body without causing any
symptoms, so many women do not realize they are
infected with it.

This procedure typically is used to diagnose Down
syndrome while a developing child is still in the womb,
at 15-28 weeks.

This is a routine urine test or pelvic exam with no
side effects.

During amniocentesis, a doctor inserts a needle
through a woman’s vaginal canal and inside her cervix. Using ultrasound as a guide, the doctor pierces the
uterus to withdraw a sample of fluid from the amniotic
sac. Afterwards, tiny cells shed by the fetus can be
studied in the laboratory. Scientists can analyze
DNA samples to determine if the fetus has Down
syndrome or other genetic conditions. Amniocentesis
also can determine the sex of the fetus.
Women who have a history of recurring miscarriages may not want to have this procedure.
Amniocentesis is usually performed in a doctor’s
office on an outpatient basis.
Common side effects include cramping and
bleeding.
234

Women who have had a prior child with GBS, or
who have a fever or prolonged or premature rupture of
the amniotic sac may be at higher risk for this type of
infection.

To test for the presence of GBS, doctors may take
a urine sample. They also may collect samples from the
vagina or rectum, which are then analyzed in a lab.
This test is usually performed late in pregnancy, at
35-37 weeks of gestation.

In many cases, doctors do not find any evidence of
this type of infection.
If a woman is found to be infected with Group B
strep, physicians usually wait to treat it until just
before labor begins. At that time, they may give the
mother antibiotics so the baby is not born with the
infection. Newborns who are exposed to Group B
strep can have inflammation of the brain, spinal
cord, blood or lungs. In some cases, this serious complication can result in infant death.
Resources
BOOKS

Planning your Pregnancy and Birth. Washington, DC: The
American College of Obstetricians and Gynecologists,
2000.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Parkey, Paula. ‘‘Birth Defects: Is Prenatal Screening
Advisable?’’ CBS HealthWatch April, 2000. <http://
www.cbshealthwatch.com/cx/viewarticle/214798>.

Amniotic fluid—The liquid that surrounds the baby
within the amniotic sac. Because it is composed
mostly of fetal urine, a low amount of fluid can indicate inadequate placental blood flow to the fetus.
Deceleration—A decrease in the fetal heart rate
that can indicate inadequate blood flow through
the placenta.
Oxytocin—A natural hormone that produces uterine contractions.

ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th St., S.W., P.O. Box 96920, Washington, DC
20090-6920. <http://www.acog.org>.
March of Dimes Birth Defects Foundation. 275
Mamaroneck Avenue, White Plains, NY 10605. (888)
663-4637. <http://www.modimes.org>.

Melissa Knopper

Ultrasound—A procedure in which highfrequency sound waves are used to create a picture
of the baby, used alone or with antepartum tests.
Vibroacoustic stimulation—In the biophysical profile, use of an artificial larynx to produce a loud
noise to ‘‘awaken’’ the fetus.

I Antepartum testing
Definition
Antepartum testing consists of a variety of tests
performed late in pregnancy to verify fetal well-being,
as judged by the baby’s heart rate and other characteristics. Antepartum tests include the nonstress test
(NST), biophysical profile, and contraction stress
test (CST).

Purpose
Antepartum testing is performed after 32 weeks of
pregnancy so that the couple and the doctor can be
warned of any problems that may necessitate further
testing or immediate delivery. The results reflect the
adequacy of blood flow (and oxygen delivery) to the
fetus from the placenta.
Antepartum tests are usually done in pregnancies
at high risk for fetal complications. Various reasons
include:


any chronic illness in the mother, such as high blood
pressure or diabetes



problems with previous pregnancies, such as
stillbirth



fetal complications, such as intrauterine growth retardation (a slowing of growth of the fetus) or birth
defects



problems in the current pregnancy, including preeclampsia (serious pregnancy-induced high blood
pressure), gestational (pregnancy-related) diabetes,
premature rupture of the membranes, excessive
amniotic fluid (the liquid that surrounds the fetus),
vaginal bleeding, or placenta previa (a condition in

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which the placenta is positioned over the cervix
instead of near the top of the uterus)


twins or other multiple fetuses

One of the most common indications for antepartum testing is post-term pregnancy. A pregnancy
should not be allowed to continue past 42 weeks.
(The usual pregnancy is 40 weeks in duration).
Babies should be monitored with antepartum testing
starting at 41 weeks. After 41 weeks, there is an
increasing risk that the placenta cannot meet the growing baby’s needs for oxygen and nutrition. This may be
reflected in decreased movements of the baby,
decreased amniotic fluid, and changes in the heart
rate pattern of the baby.

Description
Technology
The NST and CST use a technique called electronic fetal monitoring to evaluate the heartbeat of the
fetus. The biophysical profile is an ultrasound
examination.
NST
The NST is usually the first antepartum test used to
verify fetal well-being. It is based on the principle that
when the fetus moves, its heartbeat normally speeds up.
The NST assesses fetal health through monitoring
accelerations of the heart rate in response to the
baby’s own movements, i.e., in the absence of stress.
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Antepartum testing

PERIODICALS

Antepartum testing

The mother lays down or sits, and an electronic
fetal monitor is placed on her abdomen to monitor the
fetal heart rate. The doctor records the baby’s heartbeat on a graph or ‘‘tracing’’ to determine whether it
demonstrates correct reactivity, or acceleration of the
heart rate. To record fetal movements on the tracing,
the mother presses a button every time she feels the
baby move. If the baby is inactive, the mother may be
asked to rub her abdomen to ‘‘awaken’’ it. Sometimes
an instrument is used to produce a loud noise to arouse
the fetus (vibroacoustic stimulation). The test usually
takes between 20–45 minutes.
A baby who is receiving enough oxygen should
move at least twice in a 20 minute period. The baby’s
heart rate should increase at least 20 beats per minute
for at least 20 seconds during these movements. The
NST is the simplest and cheapest antepartum test.
Biophysical profile
The biophysical profile is an ultrasound exam that
can add additional information to the NST. During
the biophysical profile, the examiner checks for various characteristics of the baby to evaluate its overall
health. These include: fetal movement, fetal tone,
breathing movements, and the amniotic fluid volume.
Amniotic fluid volume is important because a
decreased amount raises the possibility that the baby
may be under stress. The five components of the test
(NST is also included) are each given a score of 2 for
normal (or present), 1 if decreased, and 0 for abnormal. The highest possible score is 10. The ‘‘modified’’
biophysical profile is another option; this includes
only the NST and amniotic fluid volume.
CST
The CST is like the NST, except that the fetus is
evaluated in response to contractions of the mother’s
uterus. Because it is a more complicated test, it is often
used after an abnormal NST to confirm the results.
Uterine contractions produce ‘‘stress’’ in the fetus
because they temporarily stop the flow of blood and
oxygen. The CST is used to confirm that the fetus does
not respond to this stress by a decrease in the heart rate.
The CST is performed with the same equipment as
the NST. Maternal blood pressure and fetal heart rate
are recorded along with the onset, relative intensity,
and duration of any spontaneous contractions. For an
accurate test, the contractions should be of sufficient
duration and frequency. If uterine activity does not
occur naturally, a drug called oxytocin may be given to
the mother intravenously (hence the test’s alternate
name, the oxytocin challenge test) to provoke
236

contractions. Another option is self-stimulation of
the mother’s nipples, because this releases natural
oxytocin. The fetal heart rate is observed until, ideally,
three moderate contractions occur within 10 minutes.

Preparation
The mother should eat just before the antepartum
tests to help stimulate fetal activity.

Risks
There are no appreciable risks from the NST or
the biophysical profile. Ultrasound used for the biophysical profile is painless and safe because it uses no
harmful radiation, and no evidence has been found
that sound waves cause any adverse effects on the
mother or fetus.
The frequency of antepartum testing depends on
the reason for its use. All of the tests occasionally give
incorrect results, which may prompt an unnecessary
early delivery or cesarean. Repeat testing is important
to double-check any abnormal findings.

Normal results
In general, ‘‘negative’’ or normal results on antepartum testing provide reassurance that the baby is
healthy and should remain so for perhaps a week, with
no need for immediate delivery. Unfortunately, the
tests cannot guarantee that there are no problems,
because falsely normal results can occur, though this
is unusual. Even if all test results are normal, it is
important to realize that this does not guarantee a
‘‘perfect’’ baby.
The NST is normal (‘‘reactive’’) if two or more
distinct fetal movements occur in association with
appropriate accelerations of the fetal heart rate within
20 minutes. A biophysical profile score of 8-10 is considered reassuring. The CST is normal if the fetus
shows no decelerations in heart rate in response to
three uterine contractions within 10 minutes.

Abnormal results
A ‘‘positive’’ result suggests that the baby is not
receiving enough oxygen for some reason. However, it
is quite possible that the test result was falsely abnormal. To confirm or monitor a suspected disorder,
follow-up testing with the same or an alternate test
will probably be performed at least weekly.
The NST is abnormal (‘‘nonreactive’’) if the fetal
heart rate fails to speed up by at least 20 beats per
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Anthrax

minute at least two times during a 20-minute period.
Abnormal decreases in the heart rate (decelerations)
are also a cause for concern.
A biophysical profile score of 6 is considered a
cause for concern and should be followed by further
testing. Scores of 4 or less may require immediate
delivery of the fetus.
Abnormal results on the CST include late decelerations, or abnormal slowing of the fetal heart rate
after the uterine contractions. This can suggest that
the baby is not receiving enough oxygen and may have
difficulty withstanding the stress of labor and vaginal
delivery. Cesarean section might be necessary so the
baby can be spared the stress of labor. With either
NST or CST, a severe deceleration (a period of very
slow heartbeat) can also suggest fetal distress.
The ultimate outcome will depend on the woman’s
individual situation. In some cases, delivery can be postponed while medication is given to the mother (e.g., for
high blood pressure) or the fetus (e.g., to speed up lung
maturity before delivery). Depending upon the readiness
of the mother’s cervix, the doctor may decide to induce
labor. The extra-large fetus of a diabetic woman may
require cesarean delivery; severe preeclampsia also may
necessitate induction of labor or cesarean section. The
doctor will determine the most prudent course of action.
Resources
PERIODICALS

Smith-Levitin, Michelle, Boris Petrikovsky, and Elizabeth P.
Schneider. ‘‘Practical Guidelines for Antepartum Fetal
Surveillance.’’ American Family Physician 56
(November 15, 1997): 1981-1988.
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th St., S.W., P.O. Box 96920, Washington, DC
20090-6920. <http://www.acog.org>.
National Institute of Child Health and Human
Development. Bldg 31, Room 2A32, MSC 2425, 31
Center Drive, Bethesda, MD 20892-2425. (800) 5052742. <http://www.nichd.nih.gov/sids/sids.htm>.

Laura J. Ninger

I Anthrax
Definition
Anthrax is an infection caused by the bacterium
Bacillus anthracis that primarily affects livestock but
GALE ENCYCLOPEDIA OF MEDICINE

Humans suffering from anthrax often develop ulcerating
nodules on the body. Custom Medical Stock Photo.
Reproduced by permission.)

that can occasionally spread to humans, affecting
either the skin, intestines, or lungs. In humans, the
infection can often be treated, but it is almost always
fatal in animals.

Description
Anthrax is most often found in the agricultural
areas of South and Central America, southern and
eastern Europe, Asia, Africa, the Caribbean, and the
Middle East. In the United States, anthrax is rarely
reported; however, cases of animal infection with
anthrax are most often reported in Texas, Louisiana,
Mississippi, Oklahoma, and South Dakota. The bacterium and its associated disease get their name from
the Greek word meaning ‘‘coal’’ because of the characteristic coal-black sore that is the hallmark of the
most common form of the disease.
During the 1800s, in England and Germany,
anthrax was known either as ‘‘wool-sorter’s’’ or ‘‘ragpicker’s’’ disease because workers contracted the disease from bacterial spores present on hides and in
wool or fabric fibers. Spores are the small, thickwalled dormant stage of some bacteria that enable
them to survive for long periods of time under adverse
conditions. The first anthrax vaccine was perfected in
1881 by Louis Pasteur.
The largest outbreak ever recorded in the United
States occurred in 1957 when nine employees of a goat
hair processing plant became ill after handling a contaminated shipment from Pakistan. Four of the five
patients with the pulmonary form of the disease died.
Other cases appeared in the 1970s when contaminated
goatskin drumheads from Haiti were brought into the
U.S. as souvenirs.
237

Anthrax

KEY TERMS
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Antitoxin—An antibody that neutralizes a toxin.
Bronchitis—Inflammation of the mucous membrane of the bronchial tubes of the lung that can
make it difficult to breathe.
Cutaneous—Pertaining to the skin
Meningitis—Inflammation of the membranes covering the brain and spinal cord called the
meninges.
Pulmonary—Having to do with the lungs or
respiratory system.
Spore—A dormant form assumed by some bacteria, such as anthrax, that enable the bacterium
to survive high temperatures, dryness, and lack of
nourishment for long periods of time. Under proper
conditions, the spore may revert to the actively
multiplying form of the bacteria.

Today, anthrax is rare, even among cattle, largely
because of widespread animal vaccination. However,
some serious epidemics continue to occur among animal herds and in human settlements in developing
countries due to ineffective control programs. In
humans, the disease is almost always an occupational
hazard, contracted by those who handle animal hides
(farmers, butchers, and veterinarians) or sort wool.
There are no reports of the disease spreading from
one person to another.
Anthrax as a weapon
There has been a great deal of recent concern
that the bacteria that cause anthrax may be used as
a type of biological warfare, since it is possible to
become infected simply by inhaling the spores, and
inhaled anthrax is the most serious form of the
disease. The bacteria can be grown in laboratories,
and with a great deal of expertise and special equipment, the bacteria can be altered to be usable as a
weapon.
The largest-ever documented outbreak of human
anthrax contracted through spore inhalation occurred
in Russia in 1979, when anthrax spores were accidentally released from a military laboratory, causing a
regional epidemic that killed 69 of its 77 victims. In
238

the United States in 2001, terrorists converted anthrax
spores into a powder that could be inhaled and mailed
it to intended targets, including news agencies and
prominent individuals in the federal government.
Because the United States government considers
anthrax to be of potential risk to soldiers, the
Department of Defense has begun systematic vaccination of all military personnel against anthrax.
For civilians in the United States, the government
has instituted a program called the National
Pharmaceutical Stockpile program in which antibiotics and other medical materials to treat two million
people are located so that they could be received anywhere in the country within twelve hours following a
disaster or terrorist attack.

Causes and symptoms
The naturally occurring bacterium Bacillus
anthracis produces spores that can remain dormant
for years in soil and on animal products, such as
hides, wool, hair, or bones. The disease is often fatal
to cattle, sheep, and goats, and their hides, wool, and
bones are often heavily contaminated.
The bacteria are found in many types of soil, all
over the world, and usually do not pose a problem for
humans because the spores stay in the ground. In
order to infect a human, the spores have to be released
from the soil and must enter the body. They can enter
the body through a cut in the skin, through consuming
contaminated meat, or through inhaling the spores.
Once the spores are in the body, and if antibiotics are
not administered, the spores become bacteria that
multiply and release a toxin that affects the immune
system. In the inhaled form of the infection, the
immune system can become overwhelmed and the
body can go into shock.
Symptoms vary depending on how the disease was
contracted, but the symptoms usually appear within
one week of exposure.
Cutaneous anthrax
In humans, anthrax usually occurs when the
spores enter a cut or abrasion, causing a skin (cutaneous) infection at the site. Cutaneous anthrax, as this
infection is called, is the mildest and most common
form of the disease. At first, the bacteria cause an
itchy, raised area like an insect bite. Within one to
two days, inflammation occurs around the raised
area, and a blister forms around an area of dying tissue
that becomes black in the center. Other symptoms may
include shivering and chills. In most cases, the bacteria
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Inhalation anthrax
Inhaling the bacterial spores can lead to a rare,
often-fatal form of anthrax known as pulmonary or
inhalation anthrax that attacks the lungs and sometimes
spreads to the brain. Inhalation anthrax begins with flulike symptoms, namely fever, fatigue, headache, muscle
aches, and shortness of breath. As early as one day after
these initial symptoms appear, and as long as two weeks
later, the symptoms suddenly worsen and progress to
bronchitis. The patient experiences difficulty breathing, and finally, the patient enters a state of shock.
This rare form of anthrax is often fatal, even if treated
within one or two days after the symptoms appear.
Intestinal anthrax
Intestinal anthrax is a rare, often-fatal form of the
disease, caused by eating meat from an animal that
died of anthrax. Intestinal anthrax causes stomach
and intestinal inflammation and sores or lesions
(ulcers), much like the sores that appear on the skin
in the cutaneous form of anthrax. The first signs of the
disease are nausea and vomiting, loss of appetite, and
fever, followed by abdominal pain, vomiting of blood,
and severe bloody diarrhea.

Diagnosis
Anthrax is diagnosed by detecting B. anthracis in
samples taken from blood, spinal fluid, skin lesions, or
respiratory secretions. The bacteria may be positively
identified using biochemical methods or using a technique whereby, if present in the sample, the anthrax
bacterium is made to fluoresce. Blood samples will
also indicate elevated antibody levels or increased
amounts of a protein produced directly in response
to infection with the anthrax bacterium. Polymerase
chain reaction (PCR) tests amplify trace amounts of
DNA to show that the anthrax bacteria are present.
Additional DNA-based tests are also currently being
perfected.

Treatment
In the early stages, anthrax is curable by administering high doses of antibiotics, but in the advanced
stages, it can be fatal. If anthrax is suspected, health
care professionals may begin to treat the patient with
antibiotics even before the diagnosis is confirmed
GALE ENCYCLOPEDIA OF MEDICINE

because early intervention is essential. The antibiotics
used include penicillin, doxycycline, and ciprofloxacin. Because inhaled spores can remain in the body for
a long time, antibiotic treatment for inhalation
anthrax should continue for 60 days. In the case of
cutaneous anthrax, the infection may be cured following a single dose of antibiotic, but it is important to
continue treatment so as to avoid potential serious
complications, such as inflammation of the membranes covering the brain and spinal cord (meningitis).
In the setting of potential bioterrorism, cutaneous
anthrax should be treated with a 60-day dose of
antibiotics.
Research is ongoing to develop new antibiotics
and antitoxins that would work against the anthrax
bacteria and the toxins they produce. One Harvard
professor, Dr. R. John Collier, and his team have been
testing two possible antitoxins on rats. A Stanford
microbiologist and a Penn State chemist have also
been testing their new antibiotic against the bacteria
that cause brucellosis and tularemia, as well as
the bacteria that cause anthrax. All of these drugs
are still in early investigational stages, however, and
it is still unknown how these drugs would affect
humans.

Prognosis
Untreated anthrax is often fatal, but death is far
less likely with appropriate care. Ten to twenty percent of patients will die from anthrax of the skin
(cutaneous anthrax) if it is not properly treated. All
patients with inhalation (pulmonary) anthrax will
die if untreated. Intestinal anthrax is fatal 25-75%
of the time.

Prevention
Anthrax is relatively rare in the United States
because of widespread animal vaccination and practices used to disinfect hides or other animal products.
Anyone visiting a country where anthrax is common
or where herd animals are not often vaccinated should
avoid contact with livestock or animal products and
avoid eating meat that has not been properly prepared
and cooked.
Other means of preventing the spread of infection
include carefully handling dead animals suspected of
having the disease, burning (instead of burying) contaminated carcasses, and providing good ventilation
when processing hides, fur, wool, or hair.
In the event that exposure to anthrax spores is
known, such as in the aftermath of a terrorist attack,
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Anthrax

remain within the sore. If, however, they spread to the
nearest lymph node (or, in rare cases, escape into the
bloodstream), the bacteria can cause a form of blood
poisoning that rapidly proves fatal.

Antiacne drugs

a course of antibiotics can prevent the disease from
occurring.
In the case of contaminated mail, as was the case in
the 2001 attacks, the U.S. postal service recommends
certain precautions. These precautions include
inspecting mail from an unknown sender for excessive
tape, powder, uneven weight or lumpy spots, restrictive
endorsements such as ‘‘Personal,’’ or ‘‘Confidential,’’ a
postmark different from the sender’s address, or a
sender’s address that seems false or that cannot be
verified. Handwashing is also recommended after
handling mail. In order to decontaminate batches of
mail before being opened, machines that use bacteriakilling radiation could be used to sterilize the mail.
These machines are similar to systems already in place
on assembly lines for sterile products, such as bandages
and medical devices, but this technique would not be
practical for large quantities of mail. In addition, the
radiation could damage some of the mail’s contents,
such as undeveloped photographic film. Microwave
radiation or the heat from a clothes iron is not powerful
enough to kill the anthrax bacteria.
For those in high-risk professions, an anthrax
vaccine is available that is 93% effective in protecting
against infection. To provide this immunity, an individual should be given an initial course of three injections, given two weeks apart, followed by booster
injections at six, 12, and 18 months and an annual
immunization thereafter.
Approximately 30% of those who have been
vaccinated against anthrax may notice mild local reactions, such as tenderness at the injection site.
Infrequently, there may be a severe local reaction
with extensive swelling of the forearm, and a few
vaccine recipients may have a more general flu-like
reaction to the shot, including muscle and joint
aches, headache, and fatigue. Reactions requiring hospitalization are very rare. However, this vaccine is only
available to people who are at high risk, including
veterinary and laboratory workers, livestock handlers,
and military personnel. The vaccine is not recommended for people who have previously recovered
from an anthrax infection or for pregnant women.
Whether this vaccine would protect against anthrax
used as a biological weapon is, as yet, unclear.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
National Institute of Allergies and Infectious Diseases,
Division of Microbiology and Infectious Diseases.
240

Building 31, Room. 7A-50, 31 Center Drive MSC 2520,
Bethesda, MD 20892. <http://www.niaid.nih.gov>.
World Health Organization, Division of Emerging and
Other Communicable Diseases Surveillance and
Control. Avenue Appia 20, 1211 Geneva 27,
Switzerland. (+00 41 22) 791 21 11. <http://
www.who.int>.
OTHER

‘‘Anthrax.’’ New York State Department of Health
Communicable Disease Fact Sheet. <http://
www.health.state.ny.us/nysdoh/consumer/
anthrax.htm>.
‘‘Bacillus anthracis (Anthrax).’’ <http://web.bu.edu/
COHIS/infxns/bacteria/anthrax.htm>.
Begley, Sharon and Karen Springen. ‘‘Anthrax: What
You Need to Know: Exposure doesn’t guarantee disease,
and the illness is treatable.’’ Newsweek October 29,
2001: 40.
Centers for Disease Control. <http://www.cdc.gov>.
Kolata, Gina. ‘‘Antibiotics and Antitoxins.’’ New York
Times October 23, 2001: Section D, page 4, second
column.
Park, Alice. ‘‘Anthrax: A Medical Guide.’’ Time 158, no. 19
(October 29, 2001): 44.
Shapiro, Bruce. ‘‘Anthrax Anxiety.’’ The Nation 273, no. 4
(November 5, 2001): 4.
Wade, Nicholas. ‘‘How a Patient Assassin Does Its Deadly
Work.’’ New York Times October 23, 2001: Section D,
page 1.

Carol A. Turkington

I Antiacne drugs
Definition
Antiacne drugs are medicines that help clear up
pimples, blackheads, whiteheads, and more severe
forms of acne.

Purpose
Different types of antiacne drugs are used for
different purposes. For example, lotions, soaps, gels,
and creams containing benzoyl peroxide or tretinoin
may be used to clear up mild to moderately severe
acne. Isotretinoin (Accutane) is prescribed only for
very severe, disfiguring acne.
Acne is a skin condition that occurs when pores or
hair follicles become blocked. This blockage allows a
waxy material called sebum to collect inside the pores
or follicles. Normally, sebum flows out onto the skin
GALE ENCYCLOPEDIA OF MEDICINE

Brand Name (Generic Name)
Accutane (isotretinoin)
Benzamycin
Cleocin T(clindamycin
phosphate)
Desquam-E(benzoyl peroxide)
Erythromycin topical (A/T/S,
erycette, t-stat)
Minocin (minocycline
hydrochloride)
Retin-A (tretinoin)

Possible Common Side Effects
Include:
Dry skin, dry mouth, conjunctivitis
Dry and itchy skin
Dry skin
Itching, red and peeling skin
Burning, dry skin, hives, red and
peeling skin
Headache, hives, diarrhea, peeling
skin, vomiting
Darkening of the skin, blistering,
crusted, or puffy skin

and hair to form a protective coating, but when it
cannot get out, small swellings develop on the skin
surface. Bacteria and dead skin cells can also collect
that can cause inflammation. Swellings that are small
and not inflamed are whiteheads or blackheads. When
they become inflamed, they turn into pimples. Pimples
that fill with pus are called pustules.
The severity of acne is often influenced by seasonal changes; it is typically less severe in summer than in
winter. In addition, acne in girls is often affected by the
menstrual cycle.
Acne cannot be cured, but acne drugs can help
clear the skin. Benzoyl peroxide and tretinoin work
by mildly irritating the skin. This encourages skin
cells to slough off, which helps open blocked pores.
Benzoyl peroxide also kills bacteria, which helps prevent whiteheads and blackheads from turning into
pimples. Isotretinoin shrinks the glands that produce
sebum.

Description
Benzoyl peroxide is found in many over-the-counter
acne products that are applied to the skin, such
as Benoxyl, Clear By Design, Neutrogena Acne,
PanOxyl, and some formulations of Clean & Clear,
Clearasil, and Oxy. Some benzoyl peroxide products
are available without a physician’s prescription; others
require a prescription. Tretinoin (Retin-A) is available
only with a physician’s prescription and comes in
liquid, cream, and gel forms, which are applied to the
skin. Isotretinoin (Accutane), which is taken by mouth
in capsule form, is available only with a physician’s
prescription. Only physicians who have experience
in diagnosing and treating severe acne, such as dermatologists, should prescribe isotretinoin.
GALE ENCYCLOPEDIA OF MEDICINE

Acne—A skin condition in which raised bumps,
pimples, and cysts form on the face, neck,
shoulders and upper back.
Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Bowel—The intestine; a tube-like structure that
extends from the stomach to the anus. Some digestive processes are carried out in the bowel before
food passes out of the body as waste.
Cyst—An abnormal sac or enclosed cavity in the
body, filled with liquid or partially solid material.
Dermatologist—A doctor who specializes in treating diseases and disorders of the skin.
Eczema—Inflammation of the skin with itching and
a rash. The rash may have blisters that ooze and
form crusts.
Pimple—A small, red swelling of the skin.
Psoriasis—A skin disease in which people have
itchy, scaly, red patches on the skin.
Pus—Thick, whitish or yellowish fluid that forms in
infected tissue.
Triglyceride—A substance formed in the body from
fat in the diet.

Some newer antiacne preparations combine
benzoyl peroxide with antibiotics. One combination
of benzoyl peroxide with clindamycin is sold under
the trade name BenzaClin.
Many antiacne preparations contain compounds
derived from plants that have anti-inflammatory
properties. One group of researchers listed thirtyeight different plants that are beneficial in treating
acne and other inflammatory skin conditions.

Recommended dosage
The recommended dosage depends on the type of
antiacne drug. These drugs usually come with written
directions for patients and should be used only as
directed. Patients who have questions about how to
use the medicine should check with a physician or
pharmacist.
Patients who use isotretinoin usually take the
medicine for a few months, then stop for at least two
months. Their acne may continue to improve even
241

Antiacne drugs

KEY TERMS

Anti-Acne Drugs

Antiacne drugs

after they stop taking the medicine. If the condition is
still severe after several months of treatment and a
two-month break, the physician may prescribe a
second course of treatment.

Precautions
Isotretinoin
Isotretinoin can cause serious birth defects, including mental retardation and physical deformities. This
medicine should not be used during pregnancy.
Women who are able to bear children should not use
isotretinoin unless they have very severe acne that has
not cleared up with the use of other antiacne drugs. In
that case, a woman who uses this drug must have a
pregnancy test two weeks before beginning treatment
and each month they are taking the drug. Another
pregnancy test must be done one month after treatment ends. The woman must use an effective birth
control method for one month before treatment begins
and must continue using it throughout treatment and
for one month after treatment ends. Women who are
able to bear children and who want to use this medicine should discuss this information with their health
care providers. Before using the medicine, they will
be asked to sign a consent form stating that they
understand the danger of taking isotretinoin during
pregnancy and that they agree to use effective birth
control.
Do not donate blood to a blood bank while taking
isotretinoin or for 30 days after treatment with the
drug ends. This will help reduce the chance of a pregnant woman receiving blood containing isotretinoin,
which could cause birth defects.
Isotretinoin may cause a sudden decrease in night
vision. If this happens, do not drive or do anything else
that could be dangerous until vision returns to normal.
Let the physician know about the problem.
This medicine may also make the eyes, nose, and
mouth dry. Ask the physician about using special eye
drops to relieve eye dryness. To temporarily relieve
the dry mouth, chew sugarless gum, suck on sugarless
candy or ice chips, or use saliva substitutes, which
come in liquid and tablet forms and are available
without a prescription. If the problem continues for
more than two weeks, check with a physician or
dentist. Mouth dryness that continues over a long
time may contribute to tooth decay and other dental
problems.
Isotretinoin may increase sensitivity to sunlight.
Patients being treated with this medicine should avoid
exposure to the sun and should not use tanning beds,
242

tanning booths, or sunlamps until they know how the
drug affects them.
In the early stages of treatment with isotretinoin,
some people’s acne seems to get worse before it starts
getting better. If the condition becomes much worse or
if the skin is very irritated, check with the physician
who prescribed the medicine.
Benzoyl peroxide and tretinoin
When applying antiacne drugs to the skin, be
careful not to get the medicine in the eyes, mouth, or
inside of the nose. Do not put the medicine on skin
that is wind burned, sunburned, or irritated, and do
not apply it to open wounds.
Because such antiacne drugs as benzoyl peroxide
and tretinoin irritate the skin slightly, avoid doing
anything that might cause further irritation. Wash
the face with mild soap and water only two or three
times a day, unless the physician says to wash it more
often. Avoid using abrasive soaps or cleansers and
products that might dry the skin or make it peel,
such as medicated cosmetics, cleansers that contain
alcohol, or other acne products that contain resorcinol, sulfur or salicylic acid.
If benzoyl peroxide or tretinoin make the skin too
red or too dry or cause too much peeling, check with a
physician. Using the medicine less often or using a
weaker strength may be necessary.
Tretinoin may increase sensitivity to sunlight.
While being treated with this medicine, avoid exposure
to the sun and do not use tanning beds, tanning
booths, or sunlamps. If it is not possible to avoid
being in the sun, use a sunscreen with a skin protection
factor (SPF) of at least 15 or wear protective clothing
over the treated areas. The skin may also become
more sensitive to cold and wind. People who use this
medicine should protect their skin from cold and wind
until they know how the medicine affects them.
Benzoyl peroxide may discolor hair or colored
fabrics.
Special conditions
People who have certain medical conditions or
who are taking certain other medicines may have problems if they use antiacne drugs. Before using these
products, be sure to let the physician know about any
of these conditions:
ALLERGIES. Anyone who has had unusual reactions
to etretinate, isotretinoin, tretinoin, vitamin A preparations, or benzoyl peroxide in the past should let his or

GALE ENCYCLOPEDIA OF MEDICINE

PREGNANCY. Women who are pregnant or who

may become pregnant should check with a physician
before using tretinoin or benzoyl peroxide. Isotretinoin
causes birth defects in humans and must not be used
during pregnancy.
BREASTFEEDING. No problems have been reported

in nursing babies whose mothers used tretinoin or
benzoyl peroxide. Women who are breastfeeding
babies should not take isotretinoin, however, as it
may cause problems in nursing babies.
OTHER MEDICAL CONDITIONS. Before using anti-

acne drugs applied to the skin, people with any of these
medical problems should make sure their physicians
are aware of their conditions:


eczema. Antiacne drugs that are applied to the skin
may make this condition worse.



sunburn or raw skin. Antiacne drugs that are applied
to the skin may increase the pain and irritation of
these conditions.

In people with certain medical conditions, isotretinoin may increase the amount of triglyceride
(a fatty-substance) in the blood. This may lead to
heart or blood vessel problems. Before using isotretinoin, people with any of these medical problems
should make sure their physicians are aware of their
conditions:


alcoholism or heavy drinking, now or in the past



diabetes (or family history of diabetes). Isotretinoin
may also change blood sugar levels.



family history of high triglyceride levels in the blood



severe weight problems.

USE OF CERTAIN MEDICINES. Using antiacne drugs
with certain other drugs may affect the way the drugs
work or may increase the chance of side effects.

Side effects
Isotretinoin
Minor discomforts such as dry mouth or nose,
dry eyes, dry skin, or itching usually go away as the
body adjusts to the drug and do not require medical
attention unless they continue or are bothersome.
Other side effects should be brought to a physicians attention. These include:


burning, redness, or itching of the eyes



nosebleeds

GALE ENCYCLOPEDIA OF MEDICINE



signs of inflammation of the lips, such as peeling,
burning, redness or pain

Bowel inflammation is not a common side effect,
but it may occur. If any of the following signs of bowel
inflammation occur, stop taking isotretinoin immediately and check with a physician:


pain in the abdomen



bleeding from the rectum



severe diarrhea
Benzoyl peroxide and tretinoin

The most common side effects of antiacne drugs
applied to the skin are slight redness, dryness, peeling,
and stinging, and a warm feeling to the skin. These
problems usually go away as the body adjusts to the
drug and do not require medical treatment.
Other side effects should be brought to a physician’s attention. Check with a physician as soon as
possible if any of the following side effects occur:


blistering, crusting or swelling of the skin



severe burning or redness of the skin



darkening or lightening of the skin. (This effect will
eventually go away after treatment with an antiacne
drug ends.)



skin rash

Other side effects are possible with any type of
antiacne drug. Anyone who has unusual symptoms
while using antiacne drugs should get in touch with
his or her physician.

Interactions
Patients using antiacne drugs on their skin should
tell their physicians if they are using any other prescription or nonprescription (over-the-counter) medicine that they apply to the skin in the same area.
Isotretinoin may interact with other medicines.
When this happens, the effects of one or both drugs
may change or the risk of side effects may be greater.
Anyone who takes isotretinoin should let the physician know about all other medicines he or she is taking
and should ask whether the possible interactions can
interfere with drug therapy. Among the drugs that
may interact with isotretinoin are:


etretinate (Tegison), used to treat severe psoriasis.
Using this medicine with isotretinoin increases side
effects.



tretinoin (Retin-A, Renova). Using this medicine
with isotretinoin increases side effects.
243

Antiacne drugs

her physician know before using an antiacne drug. The
physician should also be told about any allergies to
foods, dyes, preservatives, or other substances.

Antiandrogen drugs



vitamin A or any medicine containing vitamin A.
Using any vitamin A preparations with isotretinoin
increases side effects. Do not take vitamin supplements containing vitamin A while taking isotretinoin.



tetracyclines (used to treat infections). Using these
medicines with isotretinoin increases the chance of
swelling of the brain. Make sure the physician knows
if tetracycline is being used to treat acne or another
infection.

United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888)
INFO-FDA. <http://www.fda.gov>.

Nancy Ross-Flanigan
Rebecca J. Frey, PhD

Resources

I Antiandrogen drugs

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Acne.’’ Section 10, Chapter 116 In The Merck
Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2002.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Warts (Verrucae).’’ Section 10, Chapter 115 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Wilson, Billie Ann, Margaret T. Shannon, and Carolyn L.
Stang. Nurse’s Drug Guide 2003. Upper Saddle River,
NJ: Prentice Hall, 2003.
PERIODICALS

Breneman, D., R. Savin, C. Van dePol, et al. ‘‘Double-Blind,
Randomized, Vehicle-Controlled Clinical Trial of
Once-Daily Benzoyl Peroxide/Clindamycin Topical Gel
in the Treatment of Patients with Moderate to Severe
Rosacea.’’ International Journal of Dermatology 43
(May 2004): 381–387.
Darshan, S., and R. Doreswamy. ‘‘Patented
Antiinflammatory Plant Drug Development from
Traditional Medicine.’’ Phytotherapy Research 18 (May
2004): 343–357.
Halder, R. M., and G. M. Richards. ‘‘Topical Agents Used
in the Management of Hyperpigmentation.’’ Skin
Therapy Letter 9 (June-July 2004): 1–3.
Kligman, D. E., and Z. D. Draelos. ‘‘High-Strength
Tretinoin for Rapid Retinization of Photoaged
Facial Skin.’’ Dermatologic Surgery 30 (June 2004):
864–866.
Leyden, J. J., D. Thiboutot, and A. Shalita. ‘‘Photographic
Review of Results from a Clinical Study Comparing
Benzoyl Peroxide 5%/Clindamycin 1% Topical Gel
with Vehicle in the Treatment of Rosacea.’’ Cutis 73,
Supplement 6 (June 2004): 11–17.
ORGANIZATIONS

American Academy of Dermatology (AAD). P. O. Box
4014, Schaumburg, IL 60168-4014. (847) 330-0230.
<http://www.aad.org.>.
American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814. (301)
657-3000. <http://www.ashp.org>.

244

Definition
Antiandrogen drugs are a diverse group of medications given to counteract the effects of androgens
(male sex hormones) on various body organs and
tissues. Some medications in this category work by
lowering the body’s production of androgens while
others work by blocking the body’s ability to make
use of the androgens that are produced. The first
group of antiandrogens includes such medications as
leuprolide (Lupron, Viadur, or Eligard), goserelin
(Zoladex), triptorelin (Trelstar Depot), and abarelix
(Plenaxis). The second group includes flutamide
(Eulexin), nilutamide (Nilandron), cyproterone acetate (Cyprostat, Androcur, Cyproterone), and bicalutamide (Casodex). Flutamide, nilutamide, and
bicalutamide are nonsteroidal antiandrogen drugs
while cyproterone acetate is a steroidal medication.
Some drugs that were originally developed to treat
other conditions are sometimes categorized as antiandrogens because their off-label uses include some of
the disorders listed below. These drugs include
medroxyprogesterone (Depo-Provera), a derivative of
the female sex hormone progesterone that is used as a
contraceptive and treatment for abnormal uterine
bleeding; ketoconazole (Nizoral), an antifungal drug;
and spironolactone (Aldactone), a diuretic.

Purpose
Antiandrogen drugs may be given for any of
several conditions or disorders, ranging from skin
problems to mental disorders:


Prostate cancer. Antiandrogen medications may be
used to treat both early-stage and advanced prostate
cancer by lowering or blocking the supply of male sex
hormones that encourage the growth and spread of
the cancer.



Androgenetic alopecia. Androgenetic alopecia is a
type of hair loss that is genetically determined and
GALE ENCYCLOPEDIA OF MEDICINE



Acne. Acne is the end result of several factors, one of
which is excessive production of sebum, a whitish
semiliquid greasy substance produced by certain
glands in the skin. Antiandrogens may help to clear
acne by slowing down the secretion of sebum, which
depends on androgen production.



Amenorrhea. Amenorrhea, or the absence of menstrual periods in females of childbearing age, is sometimes caused by excessively high levels of androgens
in the blood. Antiandrogen medications may help to
restore normal menstrual periods.



Hirsutism. Hirsutism is a condition in which women
develop excessive facial and body hair in a distribution pattern usually associated with adult males.
It results from abnormally high levels of androgens
in the bloodstream or from increased sensitivity of
the hair follicles to normal levels of androgens.
Hirsutism may be a sign of polycystic ovary syndrome (PCOS), a condition in which the ovaries
develop multiple large cysts and produce too
much androgen.



Gender reassignment. Antiandrogen drugs are often
prescribed for male-to-female (MTF) transsexuals as
part of the hormonal treatment that precedes gender
reassignment surgery.



Paraphilias. Paraphilias are a group of mental disorders characterized by intense and recurrent sexual
urges or behaviors involving nonhuman objects, children or nonconsenting adults, or pain and humiliation. Antiandrogen drugs have been prescribed for
men diagnosed with paraphilias in order to lower
blood serum levels of testosterone and help them
control their sexual urges.



Virilization. Virilization is an extreme form of hyperandrogenism in females, marked by such changes
as development of male pattern baldness, voice
changes, and overdevelopment of the skeletal muscles. Antiandrogens may be given to correct this
condition.

under investigation as a possible treatment for
the paraphilias.


Goserelin. Goserelin is also an LHRH agonist, and
works in the same way as leuprolide.



Triptorelin. Triptorelin is an LHRH agonist, and
works in the same way as leuprolide. It is not usually
given to women, however.



Abarelix. Abarelix is a newer drug that works by
blocking hormone receptors in the pituitary gland.
It is recommended for the treatment of prostate cancer in men with advanced disease who refuse surgery,
cannot take other hormonal treatments, or are poor
candidates for surgery.



Ketoconazole. Ketoconazole is an antifungal drug
available in tablets to be taken by mouth. Its use in
treating hirsutism is off-label.



Flutamide. Flutamide is a nonsteroidal antiandrogen medication that blocks the use of androgen by
the body.



Nilutamide. Nilutamide is another nonsteroidal antiandrogen drug that works by blocking the body’s use
of androgens.



Bicalutamide. Bicalutamide is a nonsteroidal antiandrogen medication that works in the same way as
flutamide.



Cyproterone acetate. Cyproterone acetate is a steroidal antiandrogen drug that works by lowering testosterone production as well as blocking the body’s use
of androgens.



Medroxyprogesterone. Medroxyprogesterone is a
synthetic derivative of progesterone that prevents
ovulation and keeps the lining of the uterus from
breaking down, thus preventing uterine bleeding.



Spironolactone. Spironolactone is a potassiumsparing diuretic that may be given to treat androgen
excess in women.

Recommended dosage


Description


Leuprolide. Leuprolide is classified as a luteinizing
hormone-releasing hormone (LHRH) agonist,
which means that it resembles a chemical produced
by the hypothalamus (a gland located in the brain)
that lowers the level of testosterone in the bloodstream. It also reduces levels of estrogen in girls
and women, and may be used to treat endometriosis or tumors in the uterus. It is presently

GALE ENCYCLOPEDIA OF MEDICINE

Leuprolide. Leuprolide is available in an injectable
form and as an implant. The implant form, used to
treat prostate cancer, contains 22.5 mg of leuprolide
and is inserted under the skin every three months.
This type of slow-release medication is called depot
form. A longer-acting implant that lasts 12 months
is also available. Injectable leuprolide is injected
once a day in a 1-mg dose to treat prostate cancer.
The dosage for endometriosis or uterine tumors is
3.75 mg injected into a muscle once a month for three
to six months.
245

Antiandrogen drugs

affects both men and women. It is sometimes called
pattern baldness.

Antiandrogen drugs



Goserelin. Goserelin is implanted under the skin of
the upper abdomen. The dosage for treating cancer
of the prostate is one 3.6-mg implant every 28 days
or one 10.8-mg implant every 12 weeks. For treating
endometriosis, the dosage is one 3.6-mg implant
every 28 days for six months.



Triptorelin. Triptorelin is given as a long-lasting
injection for treatment of prostate cancer or
paraphilias. The usual dose for either condition is
3.75 mg, injected into a muscle once a month.



Abarelix. Abarelix is given in 100-mg doses by deep
injection into the muscles of the buttocks. It is given
on days 1, 15, and 29 of treatment, then every four
weeks for a total treatment duration of 12 weeks.



Ketoconazole. For treatment of hirsutism, 400 mg by
mouth once per day.



Flutamide. Flutamide is available in capsule as
well as tablet form. For treatment of prostate cancer,
250 mg by mouth three times a day. For virilization
or hyperandrogenism in women, 250 mg by mouth
three times a day. It should be used in women, however, only when other treatments have proved
ineffective.



Nilutamide. To treat prostate cancer, nilutamide is
taken in a single 300-mg daily dose by mouth for the
first 30 days of therapy, then a single daily dose of
150 mg..



Bicalutamide. Bicalutamide is taken by mouth in a
single daily dose of 50 mg to treat prostate cancer.



Cyproterone acetate. Cyproterone is taken by mouth
three times a day in 100-mg doses to treat prostate
cancer. The dose for treating hyperandrogenism or
virilization in women is one 50-mg tablet by mouth
each day for the first ten days of the menstrual cycle.
Cyproterone acetate given to treat acne is usually
given in the form of an oral contraceptive (Diane35) that combines the drug (2 mg) with ethinyl estradiol (35 mg). Diane-35 is also taken as hormonal
therapy by MTF transsexuals. The dose for treating
paraphilias is 200–400 mg by injection in depot form
every 1–2 weeks, or 50–200 mg by mouth daily.





Medroxyprogesterone. For the treatment of paraphilias, given as an intramuscular 150-mg injection
daily, weekly, or monthly, depending on the patient’s
serum testosterone levels, or as an oral dose of 100–
400 mg daily. As hormonal therapy for MTF transsexuals, 10–40 mg per day. For polycystic ovary
syndrome, 10 mg daily for 10 days.
Spironolactone. For hyperandrogenism in women,
100–200 mg per day by mouth; for polycystic ovary
syndrome, 50–200 mg per day. For the treatment of

246

acne, 200 mg per day. For hormonal therapy for
MTF transsexuals, 200–400 mg per day. A topical
form of spironolactone is available for the treatment
of androgenetic alopecia.

Precautions


Leuprolide. Leuprolide should not be used by pregnant or nursing women, by patients diagnosed with
spinal compression, or by patients allergic to the
drug. Women taking leuprolide should not try to
become pregnant, and should use methods of birth
control that do not contain hormones.



Goserelin. Goserelin should not be used during pregnancy or lactation, or by patients known to be allergic
to it. As with leuprolide, women taking goserelin
should use methods of contraception that do not
contain hormones.



Triptorelin. Patients using triptorelin should see their
doctor at regular intervals for monitoring of side
effects.



Abarelix. Abarelix should not be given to children or
women. Because of the severity of this drug’s possible
side effects, doctors who prescribe it for men must be
certified following successful completion of a safety
program for its proper use.



Ketoconazole. Ketoconazole should not be given
to alcoholic patients or those allergic to the drug. In
addition, patients using ketoconazole should have
their liver function monitored by their doctor.



Flutamide. Flutamide should not be used by pregnant women. Patients taking flutamide should have
their liver function monitored carefully. They should
notify their doctor at once if they have pain in the
upper right side of the abdomen or a yellowish discoloration of the eyes and skin, as these are signs of
liver damage. In addition, patients using this drug
should not discontinue taking it without telling their
doctor.



Nilutamide. This drug should not be given to
patients who are allergic to it, have severe respiratory
problems, or have been diagnosed with a liver disorder. Patients taking this drug should discontinue
using alcoholic beverages while they are being treated with it.



Bicalutamide. The precautions while using this drug
are the same as those for flutamide.



Cyproterone acetate. This drug has not been
approved by the Food and Drug Administration
(FDA) for use in the United States, but is approved
for use in Canada and the United Kingdom. It
GALE ENCYCLOPEDIA OF MEDICINE



Medroxyprogesterone. This drug should not be
given to patients with a history of blood clot formation in their blood vessels. It should be used with
caution in patients with asthma, seizure disorders,
migraine headaches, liver or kidney disorders, or
heart disease.



Spironolactone. This drug should not be given to
patients with overly high levels of potassium in
the blood or to patients with liver disease or kidney
failure. It should also not be given to pregnant or
lactating women.

Side effects


Leuprolide. Side effects of leuprolide in men may
include pains in the chest, groin, or legs; hot flashes,
loss of interest in sex, or impotence; bone pain; sleep
disturbances; and mood changes. Side effects in
women may include amenorrhea or light and irregular menstrual periods; loss of bone density; mood
changes; burning or itching sensations in the vagina;
or pelvic pain.



Goserelin. The side effects of goserelin may include
nausea and vomiting; they are otherwise the same as
for leuprolide.



Triptorelin. Side effects of triptorelin include pain in
the bladder, difficulty urinating, or bloody or cloudy
urine; pain in the side or lower back; hot flashes or
headache; loss of interest in sex or impotence; vomiting or diarrhea; unusual bleeding or bruising; pain at
the injection site; unusual tiredness or sleep disturbances; depression or rapid mood changes. It may
also cause a temporary enlargement of the tumor;
this side effect is known as tumor flare.

diarrhea, or gas; bluish-colored or dry skin; dizziness;
and liver damage. These side effects may be intensified in patients who smoke.


Nilutamide. The side effects of nilutamide are the
same as those for flutamide. In addition, this drug
may affect the ability of the eyes to adjust to sudden
changes in light intensity or may make the eyes unusually sensitive to light. Another potential side effect
is difficulty breathing; this is more likely to occur in
Asian patients taking this drug than in Caucasians.



Bicalutamide. The side effects of this drug are the
same as those for flutamide.



Cyproterone acetate. Cyproterone has been reported
to cause gynecomastia, impotence, loss of interest in
sex, deep venous thrombosis, and possible damage to
the cardiovascular system.



Medroxyprogesterone. The side effects of this drug
include high blood pressure, headache, nausea and
vomiting, changes in menstrual flow, breakthrough
bleeding, puffy skin (edema), weight gain, and sore or
swollen breasts.



Spironolactone. Spironolactone may cause fatigue,
headache, and drowsiness; gynecomastia and impotence in men; abdominal cramps, nausea, vomiting,
diarrhea, or loss of appetite; and skin rashes or
itching.

Interactions


Leuprolide. No interactions with other medications
have been reported.



Goserelin. No interactions have been reported.



Triptorelin. No interactions have been reported.



Abarelix. Abarelix may interact with other medications that affect heart rhythm, including procainamide, amiodarone, sotalol, and dofetilde.



Abarelix. This drug may cause immediate life-threatening allergic reactions following any dose. May
also cause a loss of bone mineral density, irregular
heartbeat, hot flashes, sleep disturbances, gynecomastia, or pain in the breasts and nipples.



Ketoconazole. Ketoconazole interacts with a number
of drugs, including rifampin, warfarin, phenytoin,
antacids, cyclosporine, terfenadine, and astemizole.
It may cause a sunburn-like skin reaction if used
together with alcohol.



Ketoconazole. The side effects of ketoconazole
include nausea and vomiting, loss of appetite,
abdominal pain, skin rash or itching, uterine bleeding, breast pain, gynecomastia, hair loss, loss of
interest in sex, and decline in sperm production.



Flutamide. This drug has been reported to intensify
the effects of warfarin (Coumadin) and other bloodthinning medications. It has also been reported to
intensify the effects of phenytoin (Dilantin), a drug
given to control seizures.



Flutamide. Flutamide has been reported to cause
breast tenderness and gynecomastia in men as well
as fatigue, nausea, flu-like symptoms, and runny
nose; darkened urine; indigestion, constipation,



Nilutamide. Reported interactions are the same as for
flutamide; in addition, nilutamide has been reported
to intensify the effects of theophylline (Theo-Dur), a
drug given to treat asthma.

GALE ENCYCLOPEDIA OF MEDICINE

247

Antiandrogen drugs

should not be used during pregnancy or lactation, or
by patients with liver disease. Men who are taking
this drug for treatment of paraphilias should not use
alcohol.

Antiandrogen drugs



Bicalutamide. Reported interactions are the same as
for flutamide.



Cyproterone acetate. Patients taking oral medications to control diabetes may require dosage adjustments while taking this drug.



Medroxyprogesterone. Patients taking phenobarbital, phenothiazine tranquilizers (chlorpromazine,
perphenazine, fluphenazine, etc.), or oral medications to control diabetes should consult their doctor
about dosage adjustments.



Spironolactone. Spironolactone is reported to
decrease the effectiveness of aspirin and anticoagulants (blood thinners). It may also interact with potassium supplements to increase the patient’s blood
potassium level.

Resources
BOOKS

‘‘Amenorrhea.’’ Section 18, Chapter 235 in The Merck
Manual of Diagnosis and Therapy, edited by Mark H.
Beers, MD, and Robert Berkow, MD. Whitehouse
Station, NJ: Merck Research Laboratories, 2005.
American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders, 4th edition, text revision.
Washington, DC: American Psychiatric Association,
2000.
‘‘Paraphilias.’’ Section 15, Chapter 192 in The Merck
Manual of Diagnosis and Therapy, edited by Mark
H. Beers, MD, and Robert Berkow, MD.
Whitehouse Station, NJ: Merck Research
Laboratories, 2005.
‘‘Prostate Cancer.’’ Section 17, Chapter 233 in The Merck
Manual of Diagnosis and Therapy, edited by Mark H.
Beers, MD, and Robert Berkow, MD. Whitehouse
Station, NJ: Merck Research Laboratories, 2005.
PERIODICALS

Bradford, J. M. ‘‘The Neurobiology, Neuropharmacology,
and Pharmacological Treatment of the Paraphilias and
Compulsive Sexual Behavior.’’ Canadian Journal of
Psychiatry 46 (February 2001): 26–34.
Brannon, Guy E., MD. ‘‘Paraphilias.’’ eMedicine, 17
October 2002. <http://www.emedicine.com/med/
topic3127.htm>.
Feinstein, Robert, MD. ‘‘Androgenetic Alopecia.’’
eMedicine, 2 October 2003. <http://www.emedicine.com/DERM/topic21.htm>.
Harper, Julie C., MD, and James Fulton, Jr., MD. ‘‘Acne
Vulgaris.’’ eMedicine, 29 July 2004. <http://www.emedicine.com/derm/topic3540.htm>.
Hunter, Melissa H., MD, and Peter J. Carek, MD.
‘‘Evaluation and Treatment of Women with
Hirsutism.’’ American Family Physician 67 (June 15,
2003): 2565–2572.
Hyperandrogenic Disorders Task Force. ‘‘American
Association of Clinical Endocrinologists Medical
248

Guidelines for Clinical Practice for the Diagnosis and
Treatment of Hyperandrogenic Disorders.’’ Endocrine
Practice 7 (March-April 2001): 120–135.
Krueger, R. B., and M. S. Kaplan. ‘‘Depot-Leuprolide
Acetate for Treatment of Paraphilias: A Report of
Twelve Cases.’’ Archives of Sexual Behavior 30 (August
2001): 409–422.
Oriel, Kathleen A., MD, MS. ‘‘Medical Care of Transsexual
Patients.’’ Journal of the Gay and Lesbian Medical
Association 4 (April 2000): 185–194.
Patel, Vipul, MD, and Raymond J. Leveille, MD. ‘‘Prostate
Cancer: Neoadjuvant Androgen Deprivation.’’
eMedicine, 10 March 2005. <http://www.emedicine.
com/med/topic3396htm>.
Richardson, Marilyn R., MD. ‘‘Current Perspectives in
Polycystic Ovary Syndrome.’’ American Family
Physician 68 (August 15, 2003): 697–704.
Thorneycroft, Ian, MD, PhD. ‘‘Androgen Excess.’’
eMedicine, 28 February 2004. <http://www.emedicine.
com/med/topic3489htm>.
ORGANIZATIONS

American Academy of Dermatology (AAD). P. O. Box
4014, Schaumburg, IL 60168-4014. (847) 330-0230.
Fax: (847) 330-0050. <http://www.aad.org>.
American Association of Clinical Endocrinologists
(AACE). 1000 Riverside Avenue, Suite 205,
Jacksonville, FL 32204. (904) 353-7878. Fax: (904)
353-8185. <http://www.aace.com>.
American Psychiatric Association (APA). 1000 Wilson
Boulevard, Suite 1825, Arlington, VA 22209-3901.
(800) 368-5777 or (703) 907-7322. Fax: (703) 907-1091.
<http://www.psych.org>.
Harry Benjamin International Gender Dysphoria
Association, Inc. (HBIGDA). 1300 South Second
Street, Suite 180, Minneapolis, MN 55454. (612)
624-9397. Fax: (612) 624-9541.
<www.hbigda.org>.
National Cancer Institute (NCI). NCI Public Inquiries
Office, Suite 3036A, 6116 Executive Boulevard,
MSC8332, Bethesda, MD 20892-8322. (800)
4-CANCER or (800) 332-8615 (TTY).
<www.nci.nih.gov>.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513 or (886)
615-NIMH. <www.nimh.nih.gov.>
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888)
INFO-FDA. <www.fda.gov>.
OTHER

National Cancer Institute (NCI). Prostate Cancer (PDQâ):
Treatment, Health Professional version. <http://
www.cancer.gov/cancertopics/pdq/treatment/prostate/
HealthProfessional/>.

Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Antianemia drugs are therapeutic agents which
increase either the number of red cells or the amount
of hemoglobin in the blood.

Purpose
Anemia is a general term for a large number of
conditions marked by a reduction in the oxygencarrying capacity of blood. Red blood cells carry
oxygen in hemoglobin, so that anemia may be caused
by a deficiency of blood or red blood cells or of hemoglobin. These conditions may be caused by a variety
of other conditions. Injury can cause blood loss, which
in turn can cause anemia. Nutritional deficiency,
inadequate amounts of some of the vitamins and
minerals that are needed for hemoglobin production,
may also cause anemia. Because hemoglobin is the
pigment that makes blood cells red, a lack of hemoglobin will cause the cells to be a paler color, leading
to the term hypochromic, lacking in color.
Other conditions can also cause anemia. For
example, certain diseases cause the condition. These
can include infections and kidney disease, in which
there is a deficiency of erythropoietin, a material produced in the kidneys which is essential for the production of red blood cells. Certain genetic conditions
affect the absorption of nutrients and may lead to
anemia. In sickle cell anemia, a genetic condition in
which the red cells are curved rather than flat, the red
cells have reduced ability to carry oxygen.
The Merck Manual reduces all types of anemia to
three classes:


blood loss



inadequate production of blood



excessive breakdown of blood cells

Anemia may be caused by one or a combination
of these three factors. Drug therapy is available for
many types of anemia; however, the selection of the
drug depends on proper diagnosis of the cause of the
anemia.

Description
Anemia caused by blood loss is normally treated
with either blood volume expanders such as plasma or
with related blood products. More severe blood loss
may require transfusions of red blood cells.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anabolic steroid—Drugs, derived from the male
sex hormones, which increase the rate of tissue
growth. They are best known for increasing the
rate of muscle development.
Anemia—Any condition in which the amount of
hemoglobin in red cells, the number of red cells,
or the size of the red cells in blood is reduced from
the normal.
Crohn’s disease—Chronic inflammation of the
intestine.
Hemochromatosis—A disorder of iron metabolism
characterized by excessive absorption of iron from
food.
Hemoglobin—The red protein found in blood cells
which carries oxygen from the lungs to the tissues.
Hemolytic anemia—A type of anemia marked by
the breakdown of red blood cells causing the
release of hemoglobin.
Sickle cell anemia—An inherited condition,
marked by crescent-shaped red blood cells and
red cell breakdown.

In some cases, blood loss may be due to ulcers of
the stomach or intestines. In these cases, treatment of
the underlying cause will normally correct the anemia.
Iron deficiency
The most common cause of anemia in adults is
iron deficiency. Although the typical American diet
contains enough iron to meet normal needs, individuals
who are less able to absorb and store iron may experience inadequate hemoglobin production. Although the
best way to meet daily iron requirements is through
improved diet, iron supplements are widely used.
Iron is normally taken in the form of ferrous
sulfate. Although other iron salts are commercially
available and make claims of fewer or less severe side
effects, these benefits may be related to the fact that
other preparations contain less iron by weight.
Ferrous sulfate contains about 37% iron, while ferrous gluconate contains only about 13% iron. People
who have trouble with the side effects of ferrous
sulfate may benefit from some of the specialty preparations available, but ferrous sulfate normally
offers the greatest amount of iron of all commercial
products.
249

Antianemia drugs

I Antianemia drugs

Antianemia drugs

Recommended dosage
Dosage should be calculated by iron needs, based
on laboratory tests. Manufacturers recommend one
tablet a day, containing 65 mg of iron, as a supplement
for patients over the age of 12 years.

Precautions
Iron can lead to lethal poisoning in children. All
iron supplements should be kept carefully out of reach
of children.
Some types of anemia do not respond to iron
therapy, and the use of iron should be avoided in
these cases. People with acquired hemolytic anemia,
autoimmune hemolytic anemia, hemochromatosis,
hemolytic anemia and hemosiderosis should not take
iron supplements. Hemolytic anemia is caused by
the increased breakdown of red blood cells.
Hemochromatosis and hemosiderosis and are conditions in which there is too much, rather than too little,
absorption of iron.
Iron supplements should also be avoided by people who have gastric or intestinal ulcers, ulcerative
colitis, or Crohn’s disease. These conditions marked
by inflammation of the digestive tract, which would be
made worse by use of iron.

Side effects
The most common side effects of iron consumption are stomach and intestinal problems, including
stomach upset with cramps, constipation, diarrhea,
nausea, and vomiting. At least 25% of patients have
one or more of these side effects. The frequency and
severity of the side effects increases with the dose of
iron. Less frequent side effects include heartburn and
urine discoloration.

Interactions
Iron supplements should not be taken at the same
time as antibiotics of either the tetracycline or quinolone types. The iron will reduce the effectiveness of the
antibiotic. Also, iron supplements reduces the effectiveness of levodopa, which is used in treatment of
Parkinson’s disease.
Iron supplements should not be used with magnesium trisilicate, an antacid, or with penicillamine,
which is used for some types of arthritis.
Taking iron with vitamin C increases the absorption of iron, with no increase in side effects.
250

Folic acid
Folic acid is found in many common foods,
including liver, dried peas, lentils, oranges, wholewheat products, asparagus, beets, broccoli, brussel
sprouts, and spinach. However, in some cases, patients
have difficulty absorbing folic acid or in converting it
from the form found in foods to the form that is active
in blood formation. In these cases, folic acid tablets are
appropriate for use.
RECOMMENDED DOSAGE. For treatment of anemia, a daily dose of 1 mg is generally used. Patients
who have trouble absorbing folic acid may require
higher doses.

Maintenance doses are:


infants: 0.1 mg/day



children (under 4 years of age): up to 0.3 mg/day



children (over 4 years of age) and adults: 0.4 mg/day



pregnant and lactating women: 0.8 mg/day

PRECAUTIONS. Before treating an anemia with
folic acid, diagnostic tests must be performed to verify
the cause of the anemia. Pernicious anemia caused by
lack of vitamin B12 shows symptoms that are very
similar to those of folic acid deficiency but also causes
nerve damage which shows up as a tingling sensation
and feelings of numbness. Giving folic acid to patients
with B12 deficiency anemia improves the blood cell
count, but the nerve damage continues to progress.
SIDE EFFECTS. Folic acid is considered extremely
safe, and there are no predictable side effects. Where
side effects have been reported, they have been among
patients taking many times more than the normal
therapeutic dose of the drug.

On rare occasions allergic reactions to folic acid
have been reported.
INTERACTIONS. Phenytoins, used to treat seizure
disorders, interact with folic acid with a reduction in
phenytoin effectiveness and an increased risk of
seizures. If the two drugs must be used together, phenytoin blood levels should be monitored, and the dose
may have to be increased.

Trimethoprim (an antibacterial) and methotrexate (originally an anti-cancer drug, which is also used
for arthritis and psoriasis) act by reducing the metabolism of folic acid. Regular blood monitoring is
required, and dose adjustments may be needed.
Vitamin B12
Vitamin B12 is also known as cyanocobalamine
and hydroxocobalamine. Cyanocobalamine may be
GALE ENCYCLOPEDIA OF MEDICINE

RECOMMENDED DOSAGE. While vitamin B12 can

be given by mouth for mild vitamin deficiency states,
pernicious anemia should always be treated with injections, either under the skin (subcutaneous) or into
muscle (intramuscular). Hydroxocobalamine should
only be injected into muscle. Intravenous injections
are not used because the vitamin is eliminated from
the body too quickly when given this way. Elderly
patients, whose ability to absorb vitamin B12 through
the stomach may be impaired, should also be treated
with injections only.
The normal dose of cyanocobalamine is 100 mcg
(micrograms) daily for six to seven days. If improvement is seen, the dose may be reduced to 100 mcg every
other day for seven doses and then 100 mcg every three
to four days for two to three weeks. After that,
monthly injections may be required for life.

Anabolic steroids
The anabolic steroids (nandrolone, oxymetholone, oxandrolone, and stanzolol) are the same drugs
that are used improperly by body builders to increase
muscle mass. Two of these drugs, nandrolone and
oxymetholone, are approved for use in treatment of
anemia. Nandrolone is indicated for treatment of anemia caused by kidney failure, while oxymetholone
may be used to treat anemia caused by insufficient
red cell production, such as aplastic anemia.
All anabolic steroids are considered to be drugs of
abuse under United States federal law.
RECOMMENDED DOSAGE. The information that
follows is specific only to oxymetholone; however,
the warnings and precautions apply to all drugs in
the class of anabolic steroids.

The dosage of oxymetholone must be individualized. The most common dose is 1 to 2 mg per kilogram
of body weight per day, although doses as high as 5 mg
per kilogram per day have been used. The response to
these drugs is slow, and it may take several months to
see if there is any benefit.
PRECAUTIONS. All anabolic steroids are dangerous. The following warnings represent the most
significant hazards of these drugs. For a complete
list, patients should consult the manufacturer’s package insert.


Peliosis hepatitis, a condition in which liver and
sometimes spleen tissue is replaced with blood-filled
cysts, has occurred in patients receiving androgenic
anabolic steroids. Although this condition is usually
reversible by discontinuing the drug, if it is left undetected and untreated, it may lead to life-threatening
liver failure or bleeding.



Liver tumors may develop. Although most of these
tumors are benign and will go away when the drug is
discontinued, liver cancers may also result.



Anabolic steroids may cause changes in blood lipids,
leading to atherosclerosis with greatly increased risk
of heart attack.



Because anabolic steroids are derived from male sex
hormones, masculinization may occur when they are
used by women.



Elderly men who use these drugs may be at increased
risk of prostate enlargement and prostate cancer.



Increased water retention due to anabolic steroids
may lead to heart failure.



Anabolic steroids should not be used during
pregnancy, since this may cause masculinization of
the fetus.

PRECAUTIONS. Although vitamin B12 has a very
high level of safety, commercial preparations may
contain preservatives which may cause allergic
responses.

In patients with pernicious anemia, treatment
with vitamin B12 may lead to loss of potassium.
Patients should be monitored for their potassium
levels.
SIDE EFFECTS. Diarrhea and itching of the skin

have been reported on rare occasions. Moreover,
there have been reports of severe allergic reactions to
cyanocobalamine.
INTERACTIONS. Aminosalicylic acid may reduce
the effectiveness of vitamin B12. Also, colchicine, a
drug used for gout, may reduce the effectiveness
of vitamin B12. Other, infrequently used drugs and
excessive use of alcohol may also affect the efficacy
of vitamin B12. Patients being treated for anemia
should discuss all medications, both prescription
and nonprescription, with their physician or
pharmacist.

GALE ENCYCLOPEDIA OF MEDICINE

251

Antianemia drugs

given by mouth, while hydroxocobalamine must be
injected. The vitamin has many functions in the
body, including maintaining the nervous system, but
in treatment of anemia B12 is needed for the metabolism of folic acid. Lack of B12 causes pernicious anemia, a type of anemia which is marked by a low red cell
count and lack of hemoglobin. There are many other
symptoms of pernicious anemia, including a feeling of
tingling or numbness, shortness of breath, muscle
weakness, faintness, and a smooth tongue. If pernicious anemia is left untreated for more than three
months, permanent damage to the nerves of the spinal
cord may result.

Antianemia drugs



Anabolic steroids should be used in children only if
there is no possible alternative. These drugs may
cause the long bones of the legs to stop growing
prematurely, leading to reduction in adult height.
Regular monitoring is essential.



In patients with epilepsy, the frequency of seizures
may be increased.



In patients with diabetes, glucose tolerance may be
altered. Careful monitoring is essential.

SIDE EFFECTS. The list of side effects associated
with anabolic steroids is extremely long. The following
list covers only the most commonly observed effects:


acne



increased urinary frequency



breast growth in males



breast pain



persistent, painful erections



masculinization in women

INTERACTIONS. Anabolic steroids should not be
used in combination with anticoagulants such as warfarin. Anabolic steroids increase the effects of the
anticoagulant, possibly leading to bleeding. If the
combination cannot be avoided, careful monitoring
is essential.

Epoetin alfa
Epoetin alfa is a synthetic form of a protein produced by the kidneys that stimulates the production
and release of red blood cells. A similar drug, darepoetin alpha, is available with the same properties, but
it remains active longer and so requires fewer injections each week. Because epoetin alfa is approved for
more types of anemia than darepoetin, this discussion
deals only with the older drug.
Epoetin alpha is approved by the Food and Drug
Administration for the following uses:


anemia associated with chronic renal failure



anemia related to zidovudine therapy in HIVinfected patients



anemia in cancer patients on chemotherapy



reduction in blood transfusions in surgical patients

In addition, epoetin alpha may be useful in anemia from many other causes. These include but are not
limited to anemia of prematurity, sickle cell anemia,
and the anemia associated with rheumatoid arthritis.
The drug has been abused by athletes due to the
theory that increasing the red blood cell count
improves athletic performance. The potential benefits
252

of misuse of the drug are limited, and the risks are
significant. The United States and International
Olympic Committees and the National Collegiate
Athletic Association consider the use of epoetin alfa
to enhance athletic ergogenic potential inappropriate
and unacceptable because its use by athletes is contrary to the rules and ethical principles of athletic
competition. As of the early 200s, tests to detect the
misuse of epoetin alfa by athletes are increasingly
reliable.
RECOMMENDED DOSAGE. Dosing schedules may
vary with the cause of the anemia. All doses should
be individualized. In general, epoetin alpha dosing
in adults is started at 50 to 100 units per kilogram
given three times a week, either by vein or subcutaneously.

The dose should be reduced if the hemoglobin
level reaches 12 grams per decaliter or if the hemoglobin level increases by more than 1 gram per decaliter in
any two-week period. The drug should be interrupted
if hemoglobin levels reach 13 grams or more per
decaliter.
The dose should be increased if the hemoglobin
level does not increase by at least 2 grams per decaliter
after eight weeks of treatment.
Maintenance doses, if required, should be individualized to keep the hemoglobin levels within the
range of 10 to 12 grams per decaliter.
PRECAUTIONS. Epoetin alpha should not be given
to patients with severe, uncontrolled hypertension.

Other conditions in which epoetin alpha should be
used only when the benefits clearly outweigh the risks
are as follows:


constitutional aplastic anemia



hypertension



thromboembolism

Side effects
The most common adverse effects of erythopoetin
alpha are:


joint pain



chest pain



diarrhea



swelling



fatigue



fever



weakness
GALE ENCYCLOPEDIA OF MEDICINE

headache



high blood pressure



irritation at injection site



nausea



vomiting



rapid heart beat

Antiangina Drugs

Brand Name (Generic Name)
Calan (calan SR, isoptin, isoptin
SR, verelan)
Cardene (nicardipine
hydrochloride)

A large number of additional adverse effects have
been reported. Patients should consult the manufacturer’s package insert for the full list.

Cardizem (diltiazem
hydrochloride)
Corgard (nadolol)

Interactions

Imdur, Ismo, Monoket
(isosorbide mononitrate)
Isordil (isosorbide dinitrate)

According to the manufacturer, as of 2004 no
evidence of interaction of epoetin alfa with other
drugs was observed.

Lopressor (metroprolol tartrate)
Nitro-Bid, Nitro-Dur, Nitrolingual
Spray, Nitrostat Tables,
Transderm-Nitro (nitroglycerin)
Norvasc (amlodipine besylate)

Resources
BOOKS

Beers, Mark H., ed. Merck Manual of Medical Information:
Home Edition. Riverside, NJ: Simon & Schuster, 2004.
Greer John P., et al., eds. Wintrobe’s Clinical Hematology.
Baltimore, MD: Lippincott Williams & Wilkins, 2003.
Physicians’ Desk Reference 2005. Montvale, NJ: Thomson
Healthcare, 2004.

Procardia, Procardia XL, Adalat
(nifedipine)
Tenormin (atenolol)

Possible Common Side Effects
Include:
Constipation, dizziness, fatigue,
headache, fluid retention, low blood
pressure, nausea
Dizziness, headache, indigestion,
nausea, rapid heartbeat, sleepiness,
swelling of feet, flushing
Dizziness, fluid retention, headache,
nausea, rash
Behaviorial changes, dizziness,
drowsiness, tiredness
Headache
Headache, dizziness, low blood
pressure
Depression, diarrhea, itching, rash,
tiredness
Dizziness, flushing, headache

Dizziness, fatigue, fluid retention,
headache, palpitations
Constipation, dizziness, hearburn,
low blood pressure, moodiness,
nausea, swelling
Dizziness, fatigue, nausea, slowed
heartbeat

PERIODICALS

Sharma, N., et al. ‘‘Vitamin supplementation: what the gastroenterologist needs to know.’’ Journal of Clinical
Gastroenterology 38, no. 10 (November/December
2004): 844–54.

Samuel D. Uretsky, PharmD

I Antiangina drugs
Definition
Antiangina drugs are medicines that relieve the
symptoms of angina pectoris (severe chest pain).

Purpose
The dull, tight chest pain of angina occurs when the
heart’s muscular wall is not getting enough oxygen. By
relaxing the blood vessels, antiangina drugs reduce the
heart’s work load and increase the amount of oxygenrich blood that reaches the heart. These drugs come in
different forms, and are used in three main ways:


taken regularly over a long period, they reduce the
number of angina attacks.

GALE ENCYCLOPEDIA OF MEDICINE



taken just before some activity that usually brings on
an attack, such as climbing stairs, they prevent attacks.



taken when an attack begins, they relieve the pain
and pressure.

Not every form of antiangina drug can be used in
every way. Some work too slowly to prevent attacks
that are about to begin or to relieve attacks that have
already started. These forms can be used only to
reduce the number of attacks. Be sure to understand
how and when to use the type of antiangina drug that
has been prescribed.

Description
Antiangina drugs, also known as nitrates, come in
many different forms: tablets and capsules that are
swallowed; tablets that are held under the tongue,
inside the lip, or in the cheek until they dissolve;
stick-on patches; ointment; and in-the-mouth sprays.
Commonly used antiangina drugs include isosorbide
dinitrate (Isordil, Sorbitrate, and other brands) and
nitroglycerin (Nitro-Bid, Nitro-Dur, Nitrolingual
Spray, Nitrostat Tablets, Transderm-Nitro, and
other brands). These medicines are available only
with a physician’s prescription.
253

Antiangina drugs



Antiangina drugs

KEY TERMS
Angina pectoris—A feeling of tightness, heaviness,
or pain in the chest, caused by a lack of oxygen in
the muscular wall of the heart.

Recommended dosage

relieved within three doses taken about 5 minutes
apart, the person should go to the hospital emergency
room as soon as possible. A heart attack may be in
progress.
Some people develop tolerance to antiangina
drugs over time. That is, the drug no longer produces
the desired effects. Anyone who seems to be developing a tolerance to this medicine should check with his
or her physician.

The recommended dosage depends on the type
and form of antiangina drug and may be different
for different patients. Check with the physician who
prescribed the drug or the pharmacist who filled the
prescription for the correct dosage.

Anyone who has had unusual reactions to antiangina drugs in the past should let his or her physician
know before taking the drugs again. The physician
should also be told about any allergies to foods,
dyes, preservatives, or other substances.

Always take antiangina drugs exactly as directed.
The medicine will not work if it is not taken correctly.

Women who are pregnant or breastfeeding or who
may become pregnant should check with their physicians before using antiangina drugs.

Do not stop taking this medicine suddenly after
taking it for several weeks or more, as this could cause
angina attacks to return. If it is necessary to stop taking
the drug, check with the physician who prescribed it
for instructions on how to taper down gradually.

Precautions
Remember that some forms of antiangina drugs
work too slowly to relieve attacks that have already
started. Check with the physician who prescribed the
medicine for instructions on how to use the type that
has been prescribed. Patients who are using sloweracting forms to make attacks less frequent may want
to ask their physicians to prescribe a fast-acting type to
relieve attacks. Another method of treating the frequency of attacks is to increase the dosage of the longacting antiangina drug. Do this only with the approval
of a physician.
These medicines make some people feel lightheaded, dizzy, or faint when they get up after sitting
or lying down. To lessen the problem, get up gradually
and hold onto something for support if possible.
Antiangina drugs may also cause dizziness, lightheadedness, or fainting in hot weather or when people stand
for a long time or exercise. Use caution in all these
situations. Drinking alcohol while taking antiangina
drugs may cause the same problems. Anyone who
takes this medicine should limit the amount of alcohol
consumed.
Because these drugs may cause dizziness, be careful when driving, using machines, or doing anything
else that could be dangerous.
If the person is taking the form of nitroglycerin
that is placed under the tongue and symptoms are not
254

Older people may be especially sensitive to the
effects of antiangina drugs and thus more likely to
have side effects such as dizziness and lightheadedness.
Before using antiangina drugs, people with any of
these medical problems should make sure their physicians are aware of their conditions:


recent heart attack or stroke



kidney disease



liver disease



severe anemia



overactive thyroid



glaucoma



recent head injury

Side effects
A common side effect is a headache just after
taking a dose of the medicine. These headaches usually
become less noticeable as the body adjusts to the drug.
Check with a physician if they are severe or they continue even after taking the medicine for a few weeks.
Unless a physician says to do so, do not change the
dose to avoid headaches. Other common side effects
include dizziness, lightheadedness, fast pulse, flushed
face and neck, nausea or vomiting, and restlessness.
These problems do not need medical attention unless
they do not go away or they interfere with normal
activities.
Other side effects may occur. Anyone who has
unusual symptoms after taking an antiangina drug
should get in touch with his or her physician.
GALE ENCYCLOPEDIA OF MEDICINE

Antiangina drugs may interact with other medicines. This may increase the risk of side effects or
change the effects of one or both drugs. Anyone who
takes antiangina drugs should let the physician know
all other medicines he or she is taking. Among the
drugs that may interact with antiangina drugs are:


other heart medicines



blood pressure medicines



aspirin



alcohol



ergot alkaloids used in migraine headaches
Nancy Ross-Flanigan

I Antiangiogenic therapy
Definition
Antiangiogenesis therapy is one of two types of
drugs in a new class of medicines that restores health
by controlling blood vessel growth. The other medication is called pro-angiogenic therapy.

Purpose
Antiangiogenic therapy inhibits the growth of new
blood vessels. Because new blood vessel growth plays a
critical role in many disease conditions, including
disorders that cause blindness, arthritis, and
cancer, angiogenesis inhibition is a ‘‘common denominator’’ approach to treating these diseases. Antiangiogenic
drugs exert their beneficial effects in a number of ways: by
disabling the agents that activate and promote cell
growth, or by directly blocking the growing blood vessel
cells. Angiogenesis inhibitory properties have been discovered in more than 300 substances, ranging from molecules produced naturally in animals and plants, such as
green tea extract, to new chemicals synthesized in the
laboratory. A number of medicines already approved
by the U.S. Food and Drug Administration (FDA)
have also been found to possess antiangiogenic properties, including celecoxib (Celebrex), bortezomib
(Velcade), and interferon. Many inhibitors are currently
being tested in clinical trials for a variety of diseases in
human patients, and some in veterinary settings.
These diseases include:


Eye disease—Excessive new blood vessels growing in
the eye can cause vision loss and lead to blindness.

GALE ENCYCLOPEDIA OF MEDICINE

Antiangiogenic treatments may prevent progressive
loss of vision or even improve eyesight in patients.


Arthritis—Blood vessels that invade the joint release
enzymes that destroy cartilage and other tissues in
arthritis. Antiangiogenic drugs may relieve the arthritic
pain and prevent bone joint destruction caused by
these pathological and destructive blood vessels.



Cancer—Tumors recruit their own private blood
supply to obtain oxygen and nourishment for cancer
cells. By cutting off tumor vasculature (the arrangement of blood vessels in the body or in a particular
organ or tissue), antiangiogenesis therapies may literally starve tumors, and prevent their growth and
spread. Antiangiogenesis may also prove to be useful
when combined with conventional chemotherapy or
radiation therapy, as part of a ‘‘multiple warhead’’
approach to attack cancer via different strategies
simultaneously.

Currently, more than 80 antiangiogenic drugs are
being tested worldwide in human clinical trials
sponsored by biotechnology and pharmaceutical companies, top medical centers, and the U.S. National
Cancer Institute. The Angiogenesis Foundation is
leading the application of antiangiogenic therapy in
veterinary medicine, for treatment of certain conditions in dogs, cats, and exotic animal species.
Pro-angiogenic therapy works the opposite way as
antiangiogenic therapy by using angiogenic growth
factors or gene therapy to stimulate blood vessel
growth in tissues that require an improved blood
supply. A number of angiogenic growth factors and
gene therapies are currently undergoing clinical trials
in human patients suffering from the following conditions: ischemic heart disease, stroke, peripheral vascular disease, and chronic wounds.

Precautions
Since antiangiogenic therapy is still experimental,
only people enrolled in a clinical trial of a particular
drug therapy can use it. The only FDA-approved
drug, bevacizumab (Avastin), is prescribed to treat
colon-rectal cancer. Avastin can result in intestinal
perforation and can cause wounds that have been
stitched to break open, sometimes causing death.
Intestinal perforation, sometimes associated with
abscesses inside the abdomen, occurred throughout
treatment with Avastin. Symptoms included abdominal pain associated with constipation and vomiting.
Avastin therapy should be permanently discontinued
in patients with intestinal perforation or wound
breaks requiring medical intervention. Serious, and
255

Antiangiogenic therapy

Interactions

Antiangiogenic therapy

KEY TERMS
Angiogenesis—The formation of new blood vessels, for example, as a result of a tumor.
Chemotherapy—The use of chemical agents to
treat diseases, infections, or other disorders, especially cancer.
Endothelial—A layer of cells that lines the inside of
certain body cavities, for example, blood vessels.
Epidermal—Referring to the thin outermost layer of
the skin, itself made up of several layers, that covers
and protects the underlying dermis (skin).
Fibroblast—A large flat cell that secretes the
proteins that form collagen and elastic fibers and
the substance between the cells of connective
tissue.
Ischemic—An inadequate supply of blood to a part
of the body, caused by partial or total blockage of
an artery.
Ocular neovascularization—Abnormal or excessive formation of blood vessels in the eye.
Peripheral vascular disease—A disease affecting
blood vessels, especially in the arms, legs, hands,
and feet.
Vascular—Relating to blood vessels.

in some cases fatal, hemoptysis (coughing up of blood
or mucus containing blood) has occurred in patients
with non-small cell lung cancer treated with chemotherapy and Avastin.

drugs to be developed that specifically damage tumorassociated blood vessels and not normal vessels. The
goal of these drugs is to attack cancers by damaging
their blood supply. Many antiangiogenic agents also
appear to hasten the death of tumor-associated blood
vessels.
With the success of targeted agents such as the
biotechnology company Genentech’s Avastin, the
only antiangiogenic drug approved by the FDA to
treat cancer, new efforts are underway to widen and
optimize the field of antiangiogenic agents. As oncology (the study of cancer) drug development accelerates,
new indications are beginning to emerge for diseases
such as ocular neovascularization and even obesity.
Antiangiogenic therapy represents a novel, potentially effective, and non-toxic treatment for cancer. It
is likely that these drugs will provide the next major
breakthrough in the management of people and pets
with cancer. Antiangiogenic therapy will likely
become part of the conventional treatment of cancer
and will be used in combination with surgery, radiation therapy and chemotherapy. These agents are
currently in clinical trials and may become available
to both people and pets in the near future.
Antiangiogenic therapy offers a number of advantages over traditional therapies for cancer:


Tumor cells often mutate and become resistant to
chemotherapy. Because antiangiogenic drugs only
target normal endothelial cells (a layer of cells that
lines the inside of certain body cavities, such as blood
vessels), these cells are less likely to develop acquired
drug resistance.



All tumors rely upon host vessels. Antiangiogenic
agents are therefore effective against a broad range
of cancers.



Conventional chemotherapy and radiotherapy indiscriminately attacks all dividing cells in the body,
leading to side effects such as diarrhea, mouth ulcers,
hair loss, and weakened immunity. Antiangiogenic
drugs selectively target dividing blood vessels and
cause fewer side effects.



Antiangiogenic drugs are relatively nontoxic and
work at levels well below the maximum tolerated
dose, so may be given in lower doses over longer
periods of time.



Antiangiogenic treatment may take weeks or even
months to exhibit its full beneficial effect, but this
allows for continuous, chronic control of disease.



Antiangiogenic drugs may also serve as a powerful
supplement to traditional chemotherapy or radiation
therapy.

Description
In the late 1990s, many medical researchers believed
that the Holy Grail of cancer treatment had been found.
Antiangiogenesis therapy was safe, elegant, and at first
apparently effective. But the clinical results soon fell
short of expectations. The tumors, it seemed, had
found a way to circumvent even this most ingenious of
treatment approaches. Despite the setbacks, however,
angiogenesis remains a very tempting target, and
researchers are exploring new agents and approaches
to maximize the effects of antiangiogenic therapies.
Newer studies have demonstrated that in addition
to differences in the regulation of new blood vessel formation in cancer compared with normal tissues, the
actual blood vessels that are ‘‘created’’ in cancers are
different from those created in normal tissues. These
differences have allowed a number of antiangiogenic
256

GALE ENCYCLOPEDIA OF MEDICINE

Since antiangiogenic drugs are either injected or
administered orally, little or no preparation is needed.
For injections, the site should be first swabbed with
alcohol.

Aftercare
Little or no aftercare is needed following the
administering of antiangiogenic therapy, except for a
small bandage on the injection site.
Although many of these agents are currently being
tested in clinical trials, no reliable way to monitor the
effects of many, if not most, of these therapeutic
agents on the inhibition of the complicated process
of angiogenesis exists. However, in late 2004, scientists
uncovered critical information that may lead to an
urgently needed method for effectively monitoring
antiangiogenic cancer therapies. The research is likely
to facilitate development of new antiangiogenic drugs
or treatment strategies and allow for accurate determination of the optimal drug doses to use for such
therapies. The researchers found that measuring peripheral blood cells can be used as a reliable way to
monitor antiangiogenic drug activity, which can be
used to help establish the optimal biologic dose of
such drugs.

Risks
In general, early research has found the side
effects of antiangiogenesis agents to be mostly minimal. Because these drugs use proteins that are produced in the human body, there is less likelihood that
they will produce the bad side effects common in
radiation treatments and chemotherapy. Still, one
cancer study found that 6 of the 99 patients taking
an antiangiogenesis drug experienced severe bleeding
in the tumors being treated. Four of those patients
died from this complication.
Since antiangiogenesis drugs could affect a
developing fetus, they will probably not be used
for pregnant women or women who might become
pregnant. They may also need to be stopped before
surgery, since blood vessels that are cut at such
times need to repair themselves. Also, people who
have damaged blood vessels (such as those with
heart disease or stroke) may not be able to take
these drugs. Other side effects in people are being
determined. Doctors, scientists and specialists at
the FDA will be monitoring these other side effects
to better understand the toxicity and risks of these
drugs.
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Since all antiangiogenic therapies are still experimental and in clinical trials, it is difficult to determine
what normal results should be. The goal of antiangiogenic drugs is to stop the development and spread of
certain diseases, especially some cancers. At least four
major proteins and their receptors and signaling pathways commonly govern angiogenesis in solid tumors:
platelet-derived growth factor, epidermal growth factor, vascular endothelial growth factor (VEGF), and
fibroblast growth factor (basic and acidic). Therapies
that either target these molecules or block their signaling pathways should be effective in preventing solid
tumor growth and spread of the cancer by preventing
the formation of new blood vessels.
Resources
BOOKS

Cooke, Robert. Dr. Folkman’s War: Angiogenesis and the
Struggle to Defeat Cancer Collingdale, PA: Diane
Publishing Co., 2003.
Teicher, Beverly A. Antiangiogenic Agents in Cancer Therapy
Totowa, NJ: Humana Press, 1999.
PERIODICALS

Frankish, Helen. ‘‘Researchers Target Tumour Blood
Vessels With Antiangiogenic Gene Therapy.’’ The
Lancet (June 29, 2002): 2256.
Guttman, Cheryl. ‘‘Anti-Angiogenic Therapy Explored for
Retinoblastoma.’’ Ophthalmology Times (September 1,
2004): 11.
March, Keith. ‘‘New Approach for Easing Angina.’’
Medical Update (December 2003): 6.
Sullivan. Michele G. ‘‘Experimental Antiangiogenic
(Therapy) May Battle Drug-Resistant Tumors.’’
Family Practice News (February 15, 2003): 42.
ORGANIZATION

The Angiogenesis Foundation. P.O. Box 382111,
Cambridge, MA 02139. (617) 576-5708. patienthelp@angio.org. or (for veterinary information) vetmed@angio.org. http://www.angio.org.

Ken R. Wells

I Antianxiety drugs
Definition
Antianxiety drugs are medicines that calm and
relax people with excessive anxiety, nervousness, or
tension, or for short-term control of social phobia
disorder or specific phobia disorder.
257

Antianxiety drugs

Preparation

Antianxiety drugs

KEY TERMS

Antianxiety Drugs

Brand Name (Generic
Name)
Atarax (hydroxyzine
hydrochloride)
Ativan (lorazepam)
BuSpar, Buspirone (buspirone hydrochloride)
Centrax (pazepam)
Librium, Libritabs
(chlordiazepoxide)
Miltown, Equanil
(meprobamate)
Serax (oxazepam)

Stelazine (trifluoperazine
hydrochloride)
Tranxene, Tranxene-SD
(clorazepate dipotassium)
Valium (diazepam)

Possible Common Side Effects Include:
Drowsiness, dry mouth
Dizziness, excessive calm, weakness
Dry mouth, dizziness, headache, fatigue,
nausea
Decreased coordination, dizziness,
drowsiness, fatigue, weakness
Constipation, drowsiness, nausea,
swelling
Diarrhea, bruising, fever, headache,
nausea, rash, slurred speech
Dizziness, fainting, headache, liver
problems, decreased coordination,
nausea, swelling, vertigo
Abnormal glucose in urine, allergic
reactions, blurred vision, constipation, eye
spasms, fluid retention and swelling
Drowsiness
Decreased coordination, drowsiness,
light-headedness

Anxiety—Worry or tension in response to real or imagined stress, danger, or dreaded situations. Physical
reactions, such as fast pulse, sweating, trembling, fatigue, and weakness may accompany anxiety.
Epilepsy—A brain disorder with symptoms that
include seizures.
Panic disorder—An disorder in which people have
sudden and intense attacks of anxiety in certain
situations. Symptoms such as shortness of breath,
sweating, dizziness, chest pain, and extreme fear
often accompany the attacks.
Phobia—An intense, abnormal, or illogical fear of
something specific, such as heights or open spaces.
Pregnancy category B—Animal studies indicate no
fetal risk, but no human studies; or adverse effects in
animals, but not in well-controlled human studies.
Pregnancy category C—No adequate human or
animal studies; or adverse fetal effects in animal
studies, but no available human data.
Seizure—A sudden attack, spasm, or convulsion.

Purpose
Antianxiety agents, or anxiolytics, may be used to
treat mild transient bouts of anxiety as well as more
pronounced episodes of social phobia and specific
phobia. Clinically significant anxiety is marked by
several symptoms. The patient experiences marked
or persistent fear of one or more social or performance
situations in which he or she is exposed to unfamiliar
people or possible scrutiny by others, and may react in
a humiliating or embarrassing way. The exposure to
the feared situation produces an anxiety attack. Fear
of these episodes of anxiety leads to avoidance behavior, which impairs normal social functioning, including working or attending classes. The patient is aware
that these fears are unjustified.

Description
In psychiatric practice, treatment of anxiety has
largely turned from traditional antianxiety agents,
anxiolytics, to antidepressant therapies. In current
use, the benzodiazepines, the best known class of anxiolytics, have been largely supplanted by selective serotonin reuptake inhibitors (SSRIs). Among the preferred
SSRIs for generalized anxiety disorder are paroxetine
(Paxil), escitalopram (Lexapro), and venlafaxine
(Effexor), which also has norepinephrine. Other
SSRIs are fluoxetine (Prozac) and sertraline (Zoloft).
258

Venlafaxine and Paroxetine have been shown particularly effective in relieving symptoms of social anxiety.
However, traditional anxiolytics remain useful for
patients who need a rapid onset of action, or whose
frequency of exposure to anxiety provoking stimuli is
low enough to eliminate the need for continued treatment. While SSRIs may require three to five weeks to
show any effects, and must be taken continuously,
benzodiazepines may produce a response within 30
minutes, and may be dosed on an as-needed basis.
The intermediate action benzodiazepines, alprazolam (Xanax), and lorazepam (Ativan) are the appropriate choice for treatment of mild anxiety and social
phobia. Diazepam (Valium) is still widely used for anxiety, but its active metabolite, desmethyldiazepam, which
has a long half-life, may make this a poorer choice than
other drugs in its class. There is considerable variation
between individuals in metabolism of benzodiazepines,
so patient response may not be predictable. As a class,
benzodiazepines are used not only as anxiolytics, but
also as sedatives, muscle relaxants, and in treatment of
epilepsy and alcoholism. The distinctions between these
uses are largely determined by onset and duration of
action, and route of administration.
Buspirone (BuSpar), which is not chemically
related to other classes of central nervous system
GALE ENCYCLOPEDIA OF MEDICINE

Benzodiazepines are controlled drugs under federal law. The number of U.S. drug-abuse related trips
to emergency departments involving benzodiazepine
medications exceeded 100,000 in 2002. Buspirone is
not a controlled substance and has no established
abuse potential.

Recommended dosage
Benzodiazepines should be administered 30 to 60
minutes before exposure to the anticipated stress.
Dosage should be individualized to minimize sedation.
The normal dose of alprazolam is 0.25–0.5 mg. The
usual dose of lorazepam is 2–3 mg. Doses may be
repeated if necessary.
Buspirone is initially dosed at 5 mg three times a
day. Patients should increase the dosage 5 mg/day, at
intervals of two to three days, as needed and should
not exceed 60 mg/day. Two to three weeks may be
required before a satisfactory response is seen.

Precautions
Benzodiazepines should not be used in patients with
psychosis, acute narrow angle glaucoma, or liver disease.
The drugs can act as respiratory depressants and should
be avoided in patients with respiratory conditions.
Benzodiazepines are potentially addictive and should
not be administered to patients with substance abuse
disorders. Because benzodiazepines are sedative, they
should be avoided in patients who must remain alert.
Their use for periods over four months has not been
documented. These drugs should not be used during the
second and third trimester of pregnancy, although use
during the first trimester appears to be safe. They should
not be taken while breastfeeding. Physicians and
pharmacists should be consulted about use in children.
Buspirone is metabolized by the liver and excreted
by the kidney, and should be used with care in patients
with hepatic or renal disease. The drug is classified as
schedule B during pregnancy, but should not be taken
during breastfeeding. Its use in children under the age
of 18 years has not been studied.
GALE ENCYCLOPEDIA OF MEDICINE

In 2004, the FDA cautioned revealed that certain
SSRIs could lead to increased risk of suicide in children and adolescents who took them for depression.
Parents should check with physicians to receive more
information on SSRIs when they are prescribed for
teens and children with anxiety.

Side effects
The most common side effects of benzodiazepines
are secondary to their CNS effects and include
sedation and sleepiness; depression; lethargy; apathy;
fatigue; hypoactivity; lightheadedness; memory impairment; disorientation; anterograde amnesia; restlessness;
confusion; crying or sobbing; delirium; headache; slurred speech; aphonia; dysarthria; stupor; seizures; coma;
syncope; rigidity; tremor; dystonia; vertigo; dizziness;
euphoria; nervousness; irritability; difficulty in concentration; agitation; inability to perform complex mental
functions; akathisia; hemiparesis; hypotonia; unsteadiness; ataxia; incoordination; weakness; vivid dreams;
psychomotor retardation; ‘‘glassy-eyed’’ appearance;
extrapyramidal symptoms; paradoxical reactions.
Other reactions include changes in heart rate and blood
pressure, changes in bowel function, severe skin rash and
changes in genitourinary function. Other adverse
effects have been reported.
Buspirone has a low incidence of side effects.
Dizziness and drowsiness are the most commonly
reported adverse effects. Other CNS effects include
dream disturbances; depersonalization, dysphoria,
noise intolerance, euphoria, akathisia, fearfulness,
loss of interest, disassociative reaction, hallucinations,
suicidal ideation, seizures; feelings of claustrophobia,
cold intolerance, stupor and slurred speech, psychosis.
Rarely, heart problems, including congestive heart
failure and myocardial infarction, have been reported.
Other adverse effects have been reported.

Interactions
The metabolism of alprazolam may be increased
by: cimetidine, oral contraceptives, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, propoxyphene, propranolol and valproic acid. The absorption
of all benzodiazepines is inhibited by concomitant use
of antacids. Benzodiazepines may increase blood
levels of digoxin, and reduce the efficacy of levodopa.
Other drug interactions have been reported.
Buspirone levels will be increased by concomitant
use of erythromycin, itraconazole, and nefazadone.
Doses should be adjusted based on clinical response.
Use of buspirone at the same time as mono-amine
259

Antianxiety drugs

drugs, is also a traditional anxiolytic, although it is
now considered either a third line or adjunctive agent
for use after trials of SSRIs and benzodiazepines. It is
appropriate for use in patients who have either failed
trials of other treatments, or who should not receive
benzodiazepines because of a history of substance
abuse problems. Buspirone, in common with antidepressants, requires a two to three week period before
there is clinical evidence of improvement, and must be
continuously dosed to maintain its effects.

Antiarrhythmic drugs

oxidase inhibitors (MAOIs, phenelzine, tranycypromine) may cause severe blood pressure elevations.
Use of buspirone with MAOIs should be avoided.
Resources
PERIODICALS

‘‘Abuse of Anti-anxiety Drugs Up, Study of ER Visits
Shows.’’ Drug Week (September 17, 2004): 225.
Finn, Robert. ‘‘Venlafaxine and Paroxetine Both Relieve
Social Anxiety.’’ Clinical Psychiatry News (September
2004): 41.
Sherman, Carl. ‘‘GAD Patients Often Require Combined
Therapy.’’ Clinical Psychiatry News (August 2004): 12–14.

Samuel D. Uretsky, PharmD
Teresa G. Odle

I Antiarrhythmic drugs
Definition
Antiarrhythmic drugs are medicines that correct
irregular heartbeats and slow down hearts that beat
too fast.

Purpose
Normally, the heart beats at a steady, even pace.
The pace is controlled by electrical signals that begin in
one part of the heart and quickly spread through the
whole heart. If something goes wrong with this control
system, the result may be an irregular heartbeat, or an
arrhythmia. Antiarrhythmic drugs correct irregular
heartbeats, restoring the normal rhythm. If the heart
is beating too fast, these drugs will slow it down. By
correcting these problems, antiarrhythmic drugs help
the heart work more efficiently.

Description
Antiarrhythmic drugs are available only with a
physician’s prescription and are sold in capsule (regular and extended release), tablet (regular and
extended-release), and injectable forms. Commonly
used antiarrhythmic drugs are disopyramide
(Norpace, Norpace CR), procainamide (Procan SR,
Pronestyl, Pronestyl-SR), and quinidine (Cardioquin,
Duraquin, Quinidex, and other brands). Do not confuse quinidine with quinine, which is a related medicine
with different uses, such as relieving leg cramps.
260

Recommended dosage
The recommended dosage depends on the type of
antiarrhythmic drug and other factors. Doses may be
different for different patients. Check with the physician who prescribed the drug or the pharmacist who
filled the prescription for the correct dosage.
Always take antiarrhythmic drugs exactly as
directed. Never take larger or more frequent doses.
Do not stop taking this medicine without checking
with the physician who prescribed it. Stopping it suddenly could lead to a serious change in heart function.
Antiarrhythmic drugs work best when they are at
constant levels in the blood. To help keep levels constant, take the medicine in doses spaced evenly through
the day and night. Do not miss any doses. If taking
medicine at night interferes with sleep, or if it is difficult
to remember to take the medicine during the day, check
with a health care professional for suggestions.

Precautions
Persons who take these drugs should see their
physician regularly. The physician will check to make
sure the medicine is working as it should and will note
any unwanted side effects.
Some people feel dizzy, lightheaded, or faint when
using these drugs. This medicine may cause blurred
vision or other vision problems. Because of these possible problems, anyone who takes these drugs should
not drive, use machines or do anything else that might
be dangerous until they have found out how the drugs
affect them. If the medicine does cause vision problems, wait until vision is clear before driving or
engaging in other activities that require normal vision.
Antiarrhythmic drugs make some people feel lightheaded, dizzy, or faint when they get up after sitting or
lying down. To lessen the problem, get up gradually
and hold onto something for support if possible.
Anyone taking this medicine should not drink
alcohol without his or her physician’s approval.
Some antiarrhythmic drugs may change the
results of certain medical tests. Before having medical
tests, anyone taking this medicine should alert the
health care professional in charge.
Anyone who is taking antiarrhythmic drugs
should be sure to tell the health care professional in
charge before having any surgical or dental procedures or receiving emergency treatment.
Antiarrhythmic drugs may cause low blood sugar
in some people. Anyone who experiences symptoms of
low blood sugar should eat or drink a food that
GALE ENCYCLOPEDIA OF MEDICINE

shakiness



unsteady walk

Anxiety—Worry or tension in response to real or
imagined stress, danger, or dreaded situations.
Physical reactions, such as fast pulse, sweating, trembling, fatigue, and weakness may accompany anxiety.
Arrhythmia—Abnormal heart rhythm.



extreme hunger



headache



nausea



drowsiness

Asthma—A disease in which the air passages of the
lungs become inflamed and narrowed.
Emphysema—A lung disease in which breathing
becomes difficult.



unusual tiredness or weakness



fast heartbeat



pale, cool skin



chills



cold sweats

Glaucoma—A condition in which pressure in the
eye is abnormally high. If not treated, glaucoma
may lead to blindness.
Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Heat stroke—A severe condition caused by prolonged exposure to high heat. Heat stroke interferes
with the body’s temperature regulating abilities and
can lead to collapse and coma.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Myasthenia gravis—A chronic disease with symptoms that include muscle weakness and sometimes
paralysis.
Palpitation—Rapid, forceful, throbbing, or fluttering heartbeat.
Prostate—A donut-shaped gland below the bladder
in men that contributes to the production of semen.
Psoriasis—A skin disease in which people have
itchy, scaly, red patches on the skin.
Systemic lupus erythematosus (SLE)—A chronic
disease that affects the skin, joints, and certain
internal organs.
Tourette syndrome—A condition in which a person has tics and other involuntary behavior, such as
barking, sniffing, swearing, grunting, and making
uncontrollable movements.
Tremor—Shakiness or trembling.

contains sugar and call a physician immediately. Signs
of low blood sugar are:
 anxiety


confusion



nervousness

GALE ENCYCLOPEDIA OF MEDICINE

Antiarrhythmic drugs



KEY TERMS

Antiarrhythmic drugs may cause dry mouth. To
temporarily relieve the discomfort, chew sugarless gum,
suck on sugarless candy or ice chips, or use saliva substitutes, which come in liquid and tablet forms and are
available without a prescription. If the problem continues for more than 2 weeks, check with a physician or
dentist. Mouth dryness that continues over a long time
may contribute to tooth decay and other dental problems.
People taking antiarrhythmic drugs may sweat
less, which can cause the body temperature to rise.
Anyone who takes this medicine should be careful
not to become overheated during exercise or hot
weather and should avoid hot baths, hot tubs, and
saunas. Overheating could lead to heat stroke.
Older people may be especially sensitive to the
effects of antiarrhythmic drugs. This may increase
the risk of certain side effects, such as dry mouth,
difficult urination, and dizziness or lightheadedness.
The antiarrhythmic drug procainamide can cause
serious blood disorders. Anyone taking this medicine
should have regular blood counts and should check
with a physician if any of the following symptoms occur:


joint or muscle pain



muscle weakness



pain in the chest or abdomen



tremors



wheezing



cough



palpitations



rash, sores, or pain in the mouth



sore throat



fever and chills



loss of appetite



diarrhea
261

Antiarrhythmic drugs



dark urine



yellow skin or eyes



unusual bleeding or bruising

OTHER MEDICAL CONDITIONS. Before using antiarrhythmic drugs, people with any of these medical
problems should make sure their physicians are aware
of their conditions:



dizziness





hallucinations

heart disorders such as structural heart disease or
inflammation of the heart muscle



depression



congestive heart failure



kidney disease



liver disease



diseases of the blood



asthma or emphysema



enlarged prostate or difficulty urinating



overactive thyroid



low blood sugar



psoriasis



glaucoma



myasthenia gravis



systemic lupus erythematosus

Special conditions
People with certain medical conditions or who are
taking certain other medicines may have problems if
they take antiarrhythmic drugs. Before taking these
drugs, be sure to let the physician know about any of
these conditions:
ALLERGIES. Anyone who has had unusual reac-

tions to an antiarrhythmic drug in the past should let
his or her physician know before taking this type of
medicine again. Patients taking procainamide should
let their physicians know if they have ever had an
unusual or allergic reaction to procaine or any other
‘‘caine-type’’ medicine, such as xylocaine or lidocaine.
Patients taking quinidine should mention any previous reactions to quinine. The physician should also
be told about any allergies to foods, dyes, preservatives, or other substances.
CONGESTIVE
HEART
DISEASE. Antiarrhythmic
drugs may cause low blood sugar, which can be a
particular problem for people with congestive heart
disease. Anyone with congestive heart disease should
be familiar with the signs of low blood sugar (listed
above) and should check with his or her physician
about what to do if such symptoms occur.
DIABETES. Antiarrhythmic drugs may cause low
blood sugar, which can be a particular problem for
people with diabetes. Anyone with diabetes should be
familiar with the signs of low blood sugar (listed
above) and should check with his or her physician
about what to do if such symptoms occur.
PREGNANCY. The effects of taking antiarrhythmic
drugs in pregnancy have not been studied in humans. In
studies of laboratory animals, this medicine increased
the risk of miscarriage. In addition, some women who
have taken these drugs while pregnant have had contractions of the uterus (womb). Women who are pregnant or who may become pregnant should check with
their physicians before taking this medicine. Women
who become pregnant while taking this medicine
should let their physicians know right away.
BREASTFEEDING. Antiarrhythmic drugs pass into

breast milk. Women who are breastfeeding should
check with their physicians before taking this medicine.
262

USE OF CERTAIN MEDICINES. Taking antiarrhythmic
drugs with certain other drugs may affect the way the
drugs work or may increase the chance of side effects.

Side effects
The most common side effects are dry mouth and
throat, diarrhea, and loss of appetite. These problems
usually go away as the body adjusts to the drug and do
not require medical treatment. Less common side
effects, such as dizziness, lightheadedness, blurred
vision, dry eyes and nose, frequent urge to urinate,
bloating, constipation, stomach pain, and decreased
sexual ability, also may occur and do not need medical
attention unless they do not go away or they interfere
with normal activities.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with the physician who prescribed the medicine
as soon as possible:


fever and chills



difficult urination



swollen or painful joints



pain when breathing



skin rash or itching

People who are especially sensitive to quinidine
may have a reaction to the first dose or doses. If any of
these side effects occur after taking quinidine, check
with a physician immediately:
GALE ENCYCLOPEDIA OF MEDICINE

dizziness



ringing in the ears

KEY TERMS



breathing problems



vision changes



fever



headache

Asthma—A disease in which the air passages of the
lungs become inflamed and narrowed.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.



skin rash

Inhalant—Medicine that is breathed into the lungs.
Mucus—Thick fluid produced by the moist membranes that line many body cavities and structures.

Other rare side effects may occur with any antiarrhythmic drug. Anyone who has unusual symptoms
after taking antiarrhythmic drugs should get in touch
with his or her physician.

Nebulizer—A device that turns liquid forms of
medicine into a fine spray that can be inhaled.

Interactions
Antiarrhythmic drugs may interact with other
medicines. When this happens, the effects of one or
both of the drugs may change or the risk of side effects
may be greater. Anyone who takes antiarrhythmic
drugs should let the physician know all other medicines he or she is taking. Among the drugs that may
interact with antiarrhythmic drugs are:


other heart medicines, including other antiarrhythmic drugs



blood pressure medicine



blood thinners



pimozide (Orap), used to treat Tourette’s syndrome

The list above does not include every drug that
may interact with antiarrhythmic drugs. Be sure to
check with a physician or pharmacist before combining antiarrhythmic drugs with any other prescription
or nonprescription (over-the-counter) medicine.

because the airways naturally expand when a person
takes a breath. The real problem arises when the person with asthma tries to breathe out. The air cannot
get out through the blocked airways, so it stays
trapped in the lungs. With each new breath, the person
can take in only a little more air, so breathing becomes
shallow and takes more and more effort.
Asthma attacks can be caused by allergies to pollen, dust, pets or other things, but people without
known allergies may also have asthma. Exercise, stress,
intense emotions, exposure to cold, certain medicines
and some medical conditions also can bring on attacks.
The two main approaches to dealing with asthma
are avoiding substances and situations that trigger
attacks and using medicines that treat or prevent the
symptoms. With a combination of the two, most people with asthma can find relief and live normal lives.

Description
Nancy Ross-Flanigan

Three types of drugs are used in treating and preventing asthma attacks:


Bronchodilators relax the smooth muscles that line
the airway. This makes the airways open wider, letting more air pass through them. These drugs are
used mainly to relieve sudden asthma attacks or to
prevent attacks that might come on after exercise.
They may be taken by mouth, injected or inhaled.
Bronchodilators may be taken in pill or liquid form,
but normally are used as inhalers, which go directly
to the lungs and result in fewer side effects.



Corticosteroids block the inflammation that narrows
the airways. Used regularly, these drugs will help prevent asthma attacks. Those attacks that do occur will
be less severe. However, corticosteroids cannot stop
an attack that is already underway. These drugs may
be taken by mouth, injected or inhaled.

I Antiasthmatic drugs
Definition
Antiasthmatic drugs are medicines that treat or
prevent asthma attacks.

Purpose
For people with asthma, the simple act of breathing can be a struggle. Their airways become inflamed
and blocked with mucus during asthma attacks, narrowing the opening through which air passes. This is
not such a problem when the person breathes in,
GALE ENCYCLOPEDIA OF MEDICINE

263

Antiasthmatic drugs



Antiasthmatic drugs





Leukotriene modifiers (montelukast and zafirlukast)
are a new type of drug that can be used in place of
steroids, for older children or adults who have a mild
degree of asthma that persists. They work by counteracting leukotrienes, which are substances released
by white blood cells in the lung that cause the air
passages to constrict and promote mucus secretion.
Leukotriene modifiers also fight off some forms of
rhinitis, an added bonus for people with asthma.
However, they are not proven effective in fighting
seasonal allergies.
Cromolyn also is taken regularly to prevent asthma
attacks and may be used alone or with other asthma
medicines. It cannot stop an attack that already has
started. The drug works by preventing certain cells in
the body from releasing substances that cause allergic reactions or asthma symptoms. One brand of this
drug, Nasalcrom, comes in capsule and nasal spray
forms and is used to treat hay fever and other allergies. The inhalation form of the drug, Intal, is used
for asthma. It comes in aerosol canisters, in capsules
that are inserted into an inhaler, and in liquid form
that is used in a nebulizer.

Precautions
Using antiasthmatic drugs properly is important.
Because bronchodilators provide quick relief, some people may be tempted to overuse them. However, with
some kinds of bronchodilators, this can lead to serious
and possibly life-threatening complications. In the long
run, patients are better off using bronchodilators only as
directed and also using corticosteroids, which eventually
will reduce their need for bronchodilators. However, a
2004 Canadian study has questioned a standard practice
of increasing steroids after asthma attacks or worsened
symptoms. Also, research in 2004 showed that people
with asthma who worked closely with their physicians to
self-manage their asthma had fewer attacks, which
reduces the need for bronchodilators. Carefully managing asthma also reduces visits to the emergency department and hospitalizations.
Corticosteroids are powerful drugs that may
cause serious side effects when used over a long time.
However, these problems are much less likely with the
inhalant forms than with the oral and injected forms.
While the oral and injected forms generally should be
used only for one to two weeks, the inhalant forms
may be used for long periods.
It is important to remember that leukotriene modifiers are used to prevent and manage asthma, not to
stop an attack. A physician or pharmacist can advise
patients on possible interactions with other drugs.
264

Patients who are using their antiasthmatic drugs
correctly but feel their asthma is not under control
should see their physicians. The physician can either
increase the dose, switch to another medicine or add
another medicine to the regimen. A 2004 survey
showed that 70% of people with mild to moderate
asthma were not taking the correct dose of asthma
medication.
When used to prevent asthma attacks, cromolyn
must be taken as directed every day. The drug may
take as long as four weeks to start working. Unless
told to do so by a physician, patients should not stop
taking the drug just because it does not seem to be
working. When symptoms do begin to improve,
patients should continue taking all medicines that
have been prescribed, unless a physician directs
otherwise.

Side effects
Inhalant forms of antiasthmatic drugs may cause
dryness or irritation in the throat, dry mouth, or an
unpleasant taste in the mouth. To help prevent these
problems, gargling and rinsing the mouth or taking a
sip of water after each dose is recommended.
More serious side effects are not common when
these medicines are used properly. However, anyone
who has unusual or bothersome symptoms after taking an antiasthmatic drug should get in touch with a
physician.

Interactions
A physician or pharmacist should be consulted
before combining antiasthmatic drugs with any other
prescription or nonprescription (over-the-counter)
medicine.
Resources
PERIODICALS

‘‘Many People With Asthma Arenót Taking the Right
Amount of Medication.’’ Obesity, Fitness & Wellness
Week (September 25, 2004): 87.
‘‘Study Calls Standard Asthma Management Into Doubt.’’
Doctor (July 15, 2004): 4.
‘‘What’s New in: Asthma and Allergic Rhinitis.’’ Pulse
(September 20, 2004): 50.

Nancy Ross-Flanigan
Teresa G. Odle

Antibacterial bath see Therapeutic baths
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Antibiotic-associated colitis is an inflammation of
the intestines that sometimes occurs following antibiotic treatment and is caused by toxins produced by the
bacterium Clostridium difficile.

Description
Antibiotic-associated colitis, also called antibioticassociated enterocolitis, can occur following antibiotic
treatment. The bacteria Clostridia difficile are normally
found in the intestines of 5% of healthy adults, but
people can also pick up the bacteria while they are in a
hospital or nursing home. In a healthy person, harmless
resident intestinal bacteria compete with each other for
food and places to ‘‘sit’’ along the inner intestinal wall.
When antibiotics are given, most of the resident bacteria
are killed. With fewer bacteria to compete with, the
normally harmless Clostridia difficile grow rapidly and
produce toxins. These toxins damage the inner wall of
the intestines and cause inflammation and diarrhea.
Although all antibiotics can cause this disease, it is
most commonly caused by clindamycin (Cleocin), ampicillin (Omnipen), amoxicillin (Amoxil, Augmentin, or
Wymox), and any in the cephalosporin class (such as
cefazolin or cephalexin). Symptoms of the condition can
occur during antibiotic treatment or within four weeks
after the treatment has stopped.
In approximately half of cases of antibiotic-associated colitis, the condition progresses to a more severe
form of colitis called pseudomembranous enterocolitis
in which pseudomembranes are excreted in the stools.
Pseudomembranes are membrane-like collections of
white blood cells, mucus, and the protein that causes
blood to clot (fibrin) that are released by the damaged
intestinal wall.

Causes and symptoms
Antibiotic-associated colitis is caused by toxins
produced by the bacterium Clostridium difficile after
treatment with antibiotics. When most of the other
intestinal bacteria have been killed, Clostridium difficile grows rapidly and releases toxins that damage the
intestinal wall. The disease and symptoms are caused
by these toxins, not by the bacterium itself.
Symptoms of antibiotic-associated colitis usually
begin four to ten days after antibiotic treatment has
begun. The early signs and symptoms of this disease
include lower abdominal cramps, an increased need to
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Colitis—Inflammation of the colon.
Edema—Fluid accumulation in a tissue.
Endoscopy—A procedure in which a thin, lighted
instrument is inserted into the interior of a hollow
organ, such as the rectum and used to visually
inspect the inner intestinal lining.
Fibrin—A fibrous blood protein vital to coagulation
and blood clot formation.
Rectum—The last part of the intestine. Stool passes
through the rectum and out through the anal
opening.
Toxic megacolon—Acute enlargement or dilation
of the large intestine.

pass stool, and watery diarrhea. As the disease progresses, the patient may experience a general ill feeling,
fatigue, abdominal pain, and fever. If the disease proceeds to pseudomembranous enterocolitis, the patient
may also experience nausea, vomiting, large amounts
of watery diarrhea, and a very high fever (104-105 8F/
40-40.5 8C). Complications of antibiotic-associated
colitis include severe dehydration, imbalances in
blood minerals, low blood pressure, fluid accumulation in deep skin (edema), enlargement of the large
intestine (toxic megacolon), and the formation of a
tear (perforation) in the wall of the large intestine.
The Clostridium difficile toxin is found in the
stools of persons older than 60 years of age 20-100
times more frequently than in the stools of persons
who are 10-20 years old. As a result, the elderly are
much more prone to developing antibiotic-associated
colitis than younger individuals.

Diagnosis
Antibiotic-associated colitis can be diagnosed by
the symptoms and recent medical history of the
patient, by a laboratory test for the bacterial toxin,
and/or by using a procedure called endoscopy.
If the diarrhea and related symptoms occurred after
the patient received antibiotics, antibiotic-associated
colitis may be suspected. A stool sample may be analyzed
for the presence of the Clostridium difficile toxin. This
toxin test is the preferred diagnostic test for antibioticassociated colitis. One frequently used test for the toxin
involves adding the processed stool sample to a human
cell culture. If the toxin is present in the stool sample, the
cells die. It may take up to two days to get the results
265

Antibiotic-associated colitis

I Antibiotic-associated colitis

Antibiotics

from this test. A simpler test, which provides results in
two to three hours, is also available. Symptoms and toxin
test results are usually enough to diagnose the disease.
Another tool that may be useful in the diagnosis
of antibiotic-associated colitis, however, is a procedure called an endoscopy that involves inserting a
thin, lighted tube into the rectum to visually inspect
the intestinal lining. Two different types of endoscopy
procedures, the sigmoidoscopy and the colonoscopy,
are used to view different parts of the large intestine.
These procedures are performed in a hospital or doctor’s office. Patients are sedated during the procedure
to make them more comfortable and are allowed to go
home after recovering from the sedation.

then compete for space and keep the Clostridium
difficile from over-populating.
Several types of supplements can be used.
Supplements containing Lactobacillus acidophilus, the
bacteria commonly found in yogurt and some types of
milk, Lactobacillus bifidus, and Streptococcus faecium,
are available in many stores in powder, capsule, tablet,
and liquid form. Acidophilus also acts as a mild antibiotic, which helps it to reestablish itself in the intestine,
and all may aid in the production of some B vitamins
and vitamin K. These supplements can be taken individually and alternated weekly or together following one
or more courses of antibiotics.

Prognosis
Treatment
Diarrhea, regardless of the cause, is always treated
by encouraging the individual to replace lost fluids and
prevent dehydration. One method to treat antibioticassociated colitis is to simply stop taking the antibiotic
that caused the disease. This allows the normal intestinal bacteria to repopulate the intestines and inhibits
the overgrowth of Clostridium difficile. Many patients
with mild disease respond well to this and are free from
diarrhea within two weeks. It is important, however, to
make sure that the original disease for which the antibiotics were prescribed is treated.
Because of the potential seriousness of this disease,
most patients are given another antibiotic to control the
growth of the Clostridium difficile, usually vancomycin
(Vancocin) or metronidazole (Flagyl or Protostat). Both
are designed to be taken orally four times a day for 10-14
days. Upon finishing antibiotic treatment, approximately 15-20% of patients will experience a relapse of
diarrhea within one to five weeks. Mild relapses can go
untreated with great success, however, severe relapses of
diarrhea require another round of antibiotic treatment.
Instead of further antibiotic treatment, a cholestyramine
resin (Questran or Prevalite) may be given. The bacterial
toxins produced in the intestine stick to the resin and are
passed out with the resin in the stool. Unfortunately,
however, vancomycin also sticks to the resin, so these
two drugs cannot be taken at the same time. Serious
disease may require hospitalization so that the patient
can be monitored, treated, and rehydrated.

Alternative treatment
The goal of alternative treatment for antibioticassociated enterocolitis is to repopulate the intestinal
environment with microorganisms that are normal and
healthy for the intestinal tract. These microorgansisms
266

With appropriate treatment and replenishment of
fluids, the prognosis is generally excellent. One or more
relapses can occur. Very severe colitis can cause a tear
(perforation) in the wall of the large intestine that would
require major surgery. Perforation of the intestine can
cause a serious abdominal infection. Antibiotic-associated colitis can be fatal in people who are elderly
and/or have a serious underlying illness, such as cancer.

Prevention
There are no specific preventative measures for this
disease. Good general health can reduce the chance of
developing a bacterial infection that would require antibiotic treatment and the chance of picking up the
Clostridia bacteria. Maintaining good general health
can also reduce the seriousness and length of the condition, should it develop following antibiotic therapy.
Resources
OTHER

Mayo Clinic Online. March 5, 1998. <http://
www.mayohealth.org>.

Belinda Rowland, PhD

Antibiotic prophylaxis see Prophylaxis

I Antibiotics
Definition
Antibiotics may be informally defined as the subgroup of anti-infectives that are derived from bacterial
sources and are used to treat bacterial infections.
Other classes of drugs, most notably the sulfonamides,
GALE ENCYCLOPEDIA OF MEDICINE

A penicillin culture. (Photograph by P. Barber, Custom Medical
Stock Photo. Reproduced by permission.)

may be effective antibacterials. Similarly, some antibiotics may have secondary uses, such as the use of
demeclocycline (Declomycin, a tetracycline derivative) to treat the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Other antibiotics
may be useful in treating protozoal infections.

Purpose
Antibiotics are used for treatment or prevention
of bacterial infection.

Description
Classifications
Although there are several classification schemes
for antibiotics, based on bacterial spectrum (broad
versus narrow) or route of administration (injectable
versus oral versus topical), or type of activity (bactericidal vs. bacteriostatic), the most useful is based on
chemical structure. Antibiotics within a structural
class will generally show similar patterns of effectiveness, toxicity, and allergic potential.
PENICILLINS. The penicillins are the oldest class of

antibiotics, and have a common chemical structure
which they share with the cephalopsorins. The two
groups are classed as the beta-lactam antibiotics, and
are generally bacteriocidal—that is, they kill bacteria
rather than inhibiting growth. The penicillins can be
GALE ENCYCLOPEDIA OF MEDICINE

CEPHALOSPORINS. Cephalosporins and the closely
related cephamycins and carbapenems, like the pencillins, contain a beta-lactam chemical structure.
Consequently, there are patterns of cross-resistance
and cross-allergenicity among the drugs in these
classes. The ‘‘cepha’’ drugs are among the most diverse
classes of antibiotics, and are themselves subgrouped
into 1st, 2nd and 3rd generations. Each generation has
a broader spectrum of activity than the one before. In
addition, cefoxitin, a cephamycin, is highly active
against anaerobic bacteria, which offers utility in treatment of abdominal infections. The 3rd generation
drugs, cefotaxime, ceftizoxime, ceftriaxone and others,
cross the blood-brain barrier and may be used to treat
meningitis and encephalitis. Cephalopsorins are the
usually preferred agents for surgical prophylaxis.
FLUROQUINOLONES. The fluroquinolones are synthetic antibacterial agents, and not derived from bacteria.
They are included here because they can be readily interchanged with traditional antibiotics. An earlier, related
class of antibacterial agents, the quinolones, were not
well absorbed, and could be used only to treat urinary
tract infections. The fluroquinolones, which are based
on the older group, are broad-spectrum bacteriocidal
drugs that are chemically unrelated to the penicillins or
the cephaloprosins. They are well distributed into bone
tissue, and so well absorbed that in general they are as
effective by the oral route as by intravenous infusion.
TETRACYCLINES. Tetracyclines got their name
because they share a chemical structure that has four
rings. They are derived from a species of Streptomyces
bacteria. Broad-spectrum bacteriostatic agents, the tetracyclines may be effective against a wide variety of microorganisms, including rickettsia and amoebic parasites.
MACROLIDES. The macrolide antibiotics are
derived from Streptomyces bacteria, and got their
name because they all have a macrocyclic lactone
chemical structure. Erythromycin, the prototype of
this class, has a spectrum and use similar to penicillin.
Newer members of the group, azithromycin and
clarithyromycin, are particularly useful for their high

267

Antibiotics

further subdivided. The natural pencillins are based on
the original penicillin G structure; penicillinase-resistant
penicillins, notably methicillin and oxacillin, are active
even in the presence of the bacterial enzyme that inactivates most natural penicillins. Aminopenicillins such as
ampicillin and amoxicillin have an extended spectrum
of action compared with the natural penicillins;
extended spectrum penicillins are effective against a
wider range of bacteria. These generally include coverage for Pseudomonas aeruginaosa and may provide the
penicillin in combination with a penicillinase inhibitor.

Antibiotics

Antibiotic

Cell is destroyed

Cell deteriorates

Water enters

Different antibiotics destroy bacteria in different ways. Some short-circuit the processes by which bacteria receive energy.
Others disturb the structure of the bacterial cell wall, as shown in the illustration above. Still others interfere with the production
of essential proteins. (Illustration by Electronic Illustrators Group.)

KEY TERMS
Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Meningitis—Inflammation of tissues that surround
the brain and spinal cord.
Microorganism—An organism that is too small to
be seen with the naked eye.
Organism—A single, independent unit of life, such
as a bacterium, a plant or an animal.
Pregnancy category—A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B:
Animal studies indicate no fetal risk, but no
human studies; or adverse effects in animals, but
not in well-controlled human studies. Category C:
No adequate human or animal studies; or adverse
fetal effects in animal studies, but no available
human data. Category D: Evidence of fetal risk,
but benefits outweigh risks. Category X: Evidence
of fetal risk. Risks outweigh any benefits.

268

level of lung penetration. Clarithromycin has been
widely used to treat Helicobacter pylori infections,
the cause of stomach ulcers.
OTHERS. Other classes of antibiotics include the
aminoglycosides, which are particularly useful for
their effectiveness in treating Pseudomonas aeruginosa
infections; the lincosamindes, clindamycin and lincomycin, which are highly active against anaerobic
pathogens. There are other, individual drugs which
may have utility in specific infections.

Recommended dosage
Dosage varies with drug, route of administration,
pathogen, site of infection, and severity. Additional
considerations include renal function, age of patient,
and other factors. Consult manufacturers’ recommendations for dose and route.

Side effects
All antibiotics cause risk of overgrowth by nonsusceptible bacteria. Manufacturers list other major
hazards by class; however, the health care provider
should review each drug individually to assess the degree
of risk. Generally, breastfeeding is not recommended
while taking antibiotics because of risk of alteration to
GALE ENCYCLOPEDIA OF MEDICINE

or a reasonable presumption of bacterial infection. The
use of antibiotics in viral infections is to be avoided.
Avoid use of fluroquinolones for trivial infections.

Penicillins: Hypersensitivity may be common, and
cross allergenicity with cephalosporins has been reported.
Penicillins are classed as category B during pregnancy.

In severe infections, presumptive therapy with a
broad-spectrum antibiotic such as a 3rd generation
cephalosporin may be appropriate. Treatment should
be changed to a narrow spectrum agent as soon as the
pathogen has been identified. After 48 hours of treatment, if there is clinical improvement, an oral antibiotic should be considered.

Cephalopsorins: Several cephalopsorins and
related compounds have been associated with seizures.
Cefmetazole, cefoperazone, cefotetan and ceftriaxone
may be associated with a fall in prothrombin activity
and coagulation abnormalities. Pseudomembranous
colitis has been reported with cephalosporins and
other broad spectrum antibiotics. Some drugs in this
class may cause renal toxicity. Pregnancy category B.
Fluroquinolones: Lomefloxacin has been associated
with increased photosensitivity. All drugs in this class have
been associated with convulsions. Pregnancy category C.
Tetracyclines: Demeclocycline may cause increased
photosensitivity. Minocycline may cause dizziness.
Do not use tetracyclines in children under the age of
eight, and specifically avoid during periods of tooth
development. Oral tetracyclines bind to anions such as
calcium and iron. Although doxycycline and minocycline may be taken with meals, patients must be advised
to take other tetracycline antibiotics on an empty stomach, and not to take the drugs with milk or other
calcium-rich foods. Expired tetracycline should never
be administered. Pregnancy category D. Use during
pregnancy may cause alterations in bone development.
Macrolides: Erythromycin may aggravate the weakness of patients with myasthenia gravis. Azithromycin
has, rarely, been associated with allergic reactions,
including angioedema, anaphylaxis, and dermatologic
reactions, including Stevens-Johnson syndrome and
toxic epidermal necrolysis. Oral erythromycin may be
highly irritating to the stomach and when given by
injection may cause severe phlebitis. These drugs should
be used with caution in patients with liver dysfunction.
Pregnancy category B: Azithromycin, erythromycin. Pregnancy category C: Clarithromycin, dirithromycin, troleandomycin.
Aminoglycosides: This class of drugs causes kidney and ototoxicity. These problems can occur even
with normal doses. Dosing should be based on renal
function, with periodic testing of both kidney function
and hearing. Pregnancy category D.

Recommended usage
To minimize risk of adverse reactions and development of resistant strains of bacteria, antibiotics should
be restricted to use in cases where there is either known
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

‘‘Consumer Alert: Antibiotic Resistance Is Growing!’’
People’s Medical Society Newsletter 16 (August 1997): 1.

Samuel D. Uretsky, PharmD

I Antibiotics, ophthalmic
Definition
Ophthalmic antibiotics are medicines that kill bacteria that cause eye infections.

Purpose
Ophthalmic antibiotics are applied to the eye, or
under the eyelid, to treat eye infections caused by bacteria.

Description
The medicine described here, tobramycin
(Tobrex), comes in the form of eye drops or ointment.
It is available only with a physician’s prescription.

Recommended dosage
The dosages given here are typical doses. Physicians
may adjust the number of doses per day, the time
between doses, and the length of treatment with the
medicine, depending on the patient’s particular medical
problem. If the physician’s directions are different
from those given here, follow the physician’s directions.
Adults
EYE DROPS. For mild to moderate infections, use one
to two drops in the affected eye or eyes every four hours.

For severe infections, use two drops in the affected
eye or eyes every two hours until the condition improves.
269

Antibiotics, ophthalmic

infant’s intestinal flora, and risk of masking infection in
the infant. Excessive or inappropriate use may promote
growth of resistant pathogens.

Antibiotics, topical

Side effects

KEY TERMS
Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Ointment—A thick, spreadable substance that contains medicine and is meant to be used on the skin,
or, if it is specifically an ophthalmic, or ‘‘eye’’ ointment, in the eye

At that time, the physician will determine how much
to use until the infection is completely cleared up.

The main side effects of this medicine are itching,
redness, and swelling of the eye or eyelid. Allergic
reactions also are possible. If any of these symptoms
occur, call the physician who prescribed the medicine.

Interactions
Patients who are using any other prescription or
nonprescription (over-the-counter) medicines in their
eyes should check with their physicians before using
tobramycin.
Nancy Ross-Flanigan

OINTMENT. For mild to moderate infections,

squeeze a half-inch ribbon of ointment into the
affected eye or eyes two or three times a day. Do not
let the tip of the ointment tube touch the eye.
For severe infections, squeeze a half-inch ribbon
of ointment into the affected eye or eyes every three to
four hours until the condition improves. At that time,
the physician will determine how much to use until the
infection is completely cleared up.
Children
The child’s physician should determine the proper
dose.

Precautions
Use this drug as often as directed, for as long as
directed. Although the symptoms may have disappeared, the infection may not clear up completely if
the drug is stopped too soon. Therefore, the medication may be prescribed for several days after the infection appears to have cleared. However, it is just as
important to use the drug for only as long as directed.
Using it for too long may lead to the growth of bacteria that do not respond to the drug. These bacteria
may then cause infections that can be very difficult to
treat. Make sure the physician or pharmacist specifies
how long the medication is to be used.
Anyone who has had an allergic reaction to tobramycin or any other ingredients of Tobrex should not
use this medicine. Be sure to tell the physician about
any past reactions to the drug or its ingredients.
Anyone who has an allergic reaction to tobramycin
should stop using it immediately and call a physician.
Women who are pregnant or breastfeeding or who
plan to become pregnant should check with their physicians before using tobramycin.
270

I Antibiotics, topical
Definition
Topical antibiotics are medicines applied to the
skin to kill bacteria.

Purpose
Topical antibiotics help prevent infections caused
by bacteria that get into minor cuts, scrapes, and
burns. Treating minor wounds with antibiotics allows
quicker healing. If the wounds are left untreated, the
bacteria will multiply, causing pain, redness, swelling,
itching, and oozing. Untreated infections can eventually spread and become much more serious.
Different kinds of topical antibiotics kill different
kinds of bacteria. Many antibiotic first-aid products
contain combinations of antibiotics to make them
effective against a broad range of bacteria.
When treating a wound, it is not enough to simply
apply a topical antibiotic. The wound must first be
cleaned with soap and water and patted dry. After the
antibiotic is applied, the wound should be covered
with a dressing, such as a bandage or a protective gel
or spray. For many years, it was thought that wounds
heal best when exposed to the air. But now most
experts say it is best to keep wounds clean and moist
while they heal. The covering should still allow some
air to reach the wound, however.

Description
Some topical antibiotics are available without a
prescription and are sold in many forms, including
GALE ENCYCLOPEDIA OF MEDICINE

Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Conception—The union of egg and sperm to form a
fetus.

need the attention of a physician to prevent complications such as blood poisoning.
Topical antibiotics are meant to be used only on
the skin and only for only a few days at a time. If the
wound has not healed in five days, stop using the
antibiotic and call a doctor.

Fungal—Caused by a fungus.
Fungus—A member of a group of simple organisms
that are related to yeast and molds.

Do not use topical antibiotics on large areas of skin
or on open wounds. These products should not be used
to treat diaper rash in infants or incontinence rash in
adults.

Incontinence—The inability to control the bladder
or bowel.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.

Only minor cuts, scrapes, and burns should be
treated with topical antibiotics. Certain kinds of injuries may need medical care and should not be selftreated with topical antibiotics. These include:

creams, ointments, powders, and sprays. Some widely
used topical antibiotics are bacitracin, neomycin,
mupirocin, and polymyxin B. Among the products
that contain one or more of these ingredients are
Bactroban (a prescription item), Neosporin,
Polysporin, and Triple Antibiotic Ointment or Cream.

Recommended dosage
The recommended dosage depends on the type of
topical antibiotic. Follow the directions on the package label or ask a pharmacist for directions.
In general, topical antibiotics should be applied
within four hours after injury. Do not use more than
the recommended amount and do not apply it more
often than three times a day. Do not apply the medicine over large areas of skin or on open wounds.

Precautions
Many public health experts are concerned about
antibiotic resistance, a problem that can develop when
antibiotics are overused. Over time, bacteria develop
new defenses against antibiotics that once were effective
against them. Because bacteria reproduce so quickly,
these defenses can be rapidly passed on through generations of bacteria until almost all are immune to the
effects of a particular antibiotic. The process happens
faster than new antibiotics can be developed. To help
control the problem, many experts advise people to use
topical antibiotics only for short periods, that is, until
the wound heals, and only as directed. For the topical
antibiotic to work best, it should be used only to prevent infection in a fresh wound, not to treat an infection
that has already started. Wounds that are not fresh may
GALE ENCYCLOPEDIA OF MEDICINE



large wounds



deep cuts



cuts that continue bleeding



cuts that may need stitches



burns any larger than a few inches in diameter



scrapes imbedded with particles that won’t wash
away



animal bites



deep puncture wounds



eye injuries

Never use regular topical antibiotics in the eyes.
Special antibiotic products are available for treating
eye infections.
Although topical antibiotics control infections
caused by bacteria, they may allow fungal infections
to develop. The use of other medicines to treat the
fungal infections may be necessary. Check with the
physician or pharmacist.
Some people may be allergic to one or more ingredients in a topical antibiotic product. If an allergic
reaction develops, stop using the product immediately
and call a physician.
No harmful or abnormal effects have been
reported in babies whose mothers used topical antibiotics while pregnant or nursing. However, pregnant
women generally are advised not to use any drugs
during the first 3 months after conception. A woman
who is pregnant or breastfeeding or who plans to
become pregnant should check with her physician
before using a topical antibiotic.
Unless a physician says to do so, do not use topical antibiotics on children under two years of age.
271

Antibiotics, topical

KEY TERMS

Anticancer drugs

Side effects
The most common minor side effects are itching
or burning. These problems usually do not require
medical treatment unless they do not go away or they
interfere with normal activities.
If any of the following side effects occur, check
with a doctor as soon as possible:


rash



swelling of the lips and face



sweating



tightness or discomfort in the chest



breathing problems



fainting or dizziness



low blood pressure



nausea



diarrhea



hearing loss or ringing in the ears

Definition
Anticancer, or antineoplastic, drugs are used to
treat malignancies, or cancerous growths. Drug
therapy may be used alone, or in combination with
other treatments such as surgery or radiation therapy.

Purpose

Other rare side effects may occur. Anyone who
has unusual symptoms after using a topical antibiotic should get in touch with the physician who prescribed or the pharmacist who recommedned the
medication.

Interactions
Using certain topical antibiotics at the same time
as hydrocortisone (a topical corticosteroid used to
treat inflammation) may hide signs of infection or
allergic reaction. Do not use these two medicines at
the same time unless told to do so by a health care
provider.
Anyone who is using any other type of prescription or nonprescription (over-the-counter) medicine
on the skin should check with a doctor before using a
topical antibiotic.
Resources
PERIODICALS

Farley, Dixie. ‘‘Help for Cuts, Scrapes and Burns.’’ FDA
Consumer May 1996:12.

Nancy Ross-Flanigan

Antibody screening see Blood typing and
crossmatching
272

I Anticancer drugs

Anticancer drugs are used to control the growth of
cancerous cells. Cancer is commonly defined as the
uncontrolled growth of cells, with loss of differentiation and commonly, with metastasis, spread of the
cancer to other tissues and organs. Cancers are malignant growths. In contrast, benign growths remain
encapsulated and grow within a well-defined area.
Although benign tumors may be fatal if untreated,
due to pressure on essential organs, as in the case of a
benign brain tumor, surgery or radiation are the preferred methods of treating growths which have a well
defined location. Drug therapy is used when the tumor
has spread, or may spread, to all areas of the body.

Description
Several classes of drugs may be used in cancer
treatment, depending on the nature of the organ
involved. For example, breast cancers are commonly
stimulated by estrogens, and may be treated with
drugs that inactivate the sex hormones. Similarly,
prostate cancer may be treated with drugs that inactivate androgens, the male sex hormone. However, the
majority of antineoplastic drugs act by interfering
with cell growth. Since cancerous cells grow more
rapidly than other cells, the drugs target those cells
that are in the process of reproducing themselves. As a
result, antineoplastic drugs will commonly affect not
only the cancerous cells, but others cells that commonly reproduce quickly, including hair follicles,
ovaries and testes, and the blood-forming organs.
Newer methods of antineoplastic drug therapy
have taken different approaches, including angiogenesis—the inhibition of formation of blood vessels feeding the tumor and contributing to tumor growth.
Although these approaches hold promise, they are
not yet in common use. Developing new anticancer
drugs is the work of ongoing research. In 2003, a new
technique was developed to streamline the search for
effective drugs. Researchers pumped more than 23,000
chemical compounds through a screening technique to
identify those that help fight cancer while leaving
GALE ENCYCLOPEDIA OF MEDICINE

Generic (Brand Name)

Clinical Uses

Altretamine(Hexalen)

Treatment of
advanced ovarian
cancer
Commonly used in
combination with
other drugs; refractory acute lymphocytic leukemia
Lymphomas,
Hodgkin’s disease,
testicular cancer

Asparaginase(Elspar)

Bleomycin(Blenoxane)

Busulfan(Myleran)

Chronic granulocytic
leukemia

Carboplatin(Paraplatin)

Pallilation of ovarian
cancer

Carmustine

Hodgkin’s disease,
brain tumors, multiple myeloma, malignant melonoma
Chronic lymphocytic
leukemia, nonHodgkin’s
lymphomas, breast
and ovarian cancer
Treatment of bladder,
ovarian,
uterine, testicular,
head and neck
cancers
Hairy cell leukemia

Chlorambucil(Leukeran)

Cisplatin(Platinol)

Cladribine(Leustatin)

Cyclophosphamide
(Cytoxan)

Cytarabine(Cytosar-U)

Hodgkin’s disease,
non-Hodgkin’s lymphomas, neuroblastoma. Often used
with other drugs for
breast, ovarian, and
lung cancers; acute
lymphoblastic leukemia in children; multiple myeloma
Leukemias occurring
in adults and children

Dacarbazine(DTICDome)

Hodgkin’s disease,
malignant melanoma

Diethylstilbestrol (DES)
(Stilbestrol)

Breast cancer in
post-menopausal
women, prostate
cancer

Ethinyl
estradiol(Estinyl)

Advanced breast
cancer in postmenopausal women,
prostate cancer

Etoposide(VePesid)

Acute leukemias,
lymphomas, testicular cancer

Common Side
Effects To Drug
Bone marrow
depression, nausea
and vomiting
Liver, kidney,
pancreas, CNS
abnormalities,

Generic (Brand Name)

Clinical Uses

Mitomycin (Mutamycin)

Bladder, breast,
colon, lung,
pancreas, rectum
cancers, head and
neck cancer, malignant melanoma
Cancer of the adrenal
cortex (inoperable)

Mitotane (Lysodren)
Hair loss, stomatitis,
pulmonary toxicity,
hyperpigmentation
of skin
Bone marrow
depression,
pulmonary toxicity
Bone marrow
depression, nausea
and vomiting
Bone marrow
depression, nausea
and vomiting, toxic
damage to liver
Bone marrow
depression, excess
uric acid in blood

Renal toxicity and
ototoxicity

Mitoxantrone (Novantrone)

Acute nonlymphocytic leukemia

Paclitaxel (Taxol)

Advanced ovarian
cancer

Pentastatin (Nipent)

Hairy cell leukemia
unresponsive to
alpha-interferon

Pipobroman (Vercyte)

Chronic granulocytic
leukemia
Testucular tumors

Plicamycin (Mithracin)

Bone marrow
depression, nausea
and vomiting, fever
Bone marrow
depression, hair loss,
nausea and vomiting,
inflammation of the
bladder

Prednisone (Meticorten)

Procarbazine (Matulane)

Streptozocin (Zanosar)
Tamoxifen (Nolvadex)

Bone marrow
depression, nausea
and vomiting,
diarrhea, stomatitis
Bone marrow
depression, nausea
and vomiting
Hair loss, nausea and
vomiting, edema,
excess calcium in
blood; feminizing
effects in men
Excess calcium in
blood, anorexia,
edema, nausea and
vomiting; feminizing
effects in men
Bone marrow
depression, nausea
and vomiting, hair loss

GALE ENCYCLOPEDIA OF MEDICINE

Teniposide (Vumon)
Vinblastine (Velban)

Vincristine (Oncovin)

Common Side
Effects To Drug
Bone marrow
depression, nausea
and vomiting,
diarrhea, stomatitis,
possible tissue
damage
Damage to adrenal
cortex, nausea,
anorexia
Cardiac arrhythmias,
labored breating,
nausea and vomiting,
diarrhea, fever,
congestive heart
failure
Bone marrow
depression, hair loss,
nausea and vomiting,
hypotension, allergic
reactions, slow heart
action, muscle and
joint pain
Bone marrow
depression, fever,
skin rash, liver
damage, nausea and
vomiting
Bone marrow
depression
Toxicity/damage
to bone marrow,
kidneys, and liver
May be toxic to all
body systems

Used in adjunct therapy for palliation of
symptoms in lymphomas, acute leukemia
Hodgkin’s disease
Hodgkin’s disease
Bone marrow
depression, nausea
and vomiting
Islet cell carcinoma of Nausea and vomiting,
pancreas
toxicity to kidneys
Advanced breast can- Nausea and vomiting,
ocular toxicity, hot
cer in post
flashes
menopausal
Acute lymphocytic
See Etoposide
leukemia in children
Bone marrow
Breast cancer,
depression,
Hodgkin’s disease,
neurotoxicity
metastatic testicular
cancer
Constipation,
Acute leukemia,
neurotoxicity,
Hodgkin’s disease,
possible tissue
lymphomas
necrosis

healthy cells unharmed. The system identified nine
compounds matching the profile, including one previously unidentified drug for fighting cancer. They
have expanded their research to determine how the
drug might be developed. This was an important step
273

Anticancer drugs

Anti Cancer Drugs (continued)

Anti Cancer Drugs

Anticancer drugs

KEY TERMS
Cataract—Clouding of the lens of the eye, leading
to poor vision or blindness.
Impotent—Unable to achieve or maintain an erection of the penis.

in identifying anticancer dugs that are not completely
toxic to healthy cells.
Antineoplastic drugs may be divided into two
classes: cycle specific and non-cycle specific. Cycle
specific drugs act only at specific points of the cell’s
duplication cycle, such as anaphase or metaphase,
while non-cycle specific drugs may act at any point in
the cell cycle. In order to gain maximum effect, antineoplastic drugs are commonly used in combinations.

Precautions
Because antineoplastic agents do not target specific cell types, they have a number of common
adverse side effects. Hair loss is common due to the
effects on hair follicles, and anemia, immune system
impairment, and clotting problems are caused by
destruction of the blood-forming organs, leading to
a reduction in the number of red cells, white cells, and
platelets. Because of the frequency and severity of
these side effects, it is common to administer chemotherapy in cycles, allowing time for recovery from
the drug effects before administering the next dose.
Doses are often calculated, not on the basis of weight,
but rather based on blood counts, in order to avoid
dangerous levels of anemia (red cell depletion), neutropenia (white cell deficiency), or thrombocytopenia
(platelet deficiency.)
The health professional has many responsibilities
in dealing with patients undergoing chemotherapy.
The patient must be well informed of the risks and
benefits of chemotherapy, and must be emotionally
prepared for the side effects. These may be permanent,
and younger patients should be aware of the high risk
of sterility after chemotherapy.
The patient must also know which side effects
should be reported to the practitioner, since many
adverse effects do not appear until several days after
a dose of chemotherapy. When chemotherapy is selfadministered, the patient must be familiar with
proper use of the drugs, including dose scheduling
and avoidance of drug-drug and food-drug
interactions.
274

Appropriate steps should be taken to minimize
side effects. These may include administration of antinauseant medications to reduce nausea and vomiting,
maintaining fluid levels to reduce drug toxicity, particularly to the kidneys, or application of a scalp tourniquet to reduce blood flow to the scalp and minimize
hair loss due to drug therapy.
Patients receiving chemotherapy also are at risk of
infections due to reduced white blood counts. While
prophylactic antibiotics may be useful, the health care
professional should also be sure to use standard precautions, including gowns and gloves when appropriate. Patients should be alerted to avoid risks of viral
contamination, and live virus immunizations are contraindicated until the patient has fully recovered from
the effects of chemotherapy. Similarly, the patient
should avoid contact with other people who have
recently had live virus immunizations.
Other precautions which should be emphasized
are the risks to pregnant or nursing women. Because
antineoplastic drugs are commonly harmful to the
fetus, women of childbearing potential should be cautioned to use two effective methods of birth control
while receiving cancer chemotherapy. This also applies
if the woman’s male partner is receiving chemotherapy. Breastfeeding should be avoided while the mother
is being treated.
Before prescribing or administering anticancer
drugs, health care providers should inquire whether
the patient has any of the following conditions:


chickenpox or recent exposure to someone with
chickenpox



shingles (Herpes zoster)



mouth sores



current or past seizures



head injury



nerve or muscle disease



hearing problems



infection of any kind



gout



colitis



intestine blockage



stomach ulcer



kidney stones



kidney disease



liver disease



current or past alcohol abuse
GALE ENCYCLOPEDIA OF MEDICINE

immune system disease



joint pain



cataracts or other eye problems



skin rash



high cholesterol



hearing problems or ringing in the ears



numbness or tingling in the fingers or toes



trouble walking or balance problems



swelling of the feet or lower legs



unusual tiredness or weakness



loss of taste

Other precautions
The anticancer drug methotrexate has additional
precautions. Patients should be given advice on the
effects of sun exposure and the use of alcohol and pain
relievers.



seizures

Side effects



dizziness

Tamoxifen



confusion



agitation



headache



dark urine



yellow eyes or skin



flushing of the face

The anticancer drug tamoxifen (Nolvadex) increases
the risk of cancer of the uterus in some women. It also
causes cataracts and other eye problems. Women taking
this drug may have hot flashes, menstrual changes, genital itching, vaginal discharge, and weight gain. Men who
take tamoxifen may lose interest in sex or become impotent. Health care providers should keep in close contact
with patients to assess the individual risks associated
with taking this powerful drug.
Other anticancer drugs
These side effects are not common, but could be a
sign of a serious problem. Health care providers
should immediately be consulted if any of the following occur:

Anticancer drugs



In addition, there are other possible side effects
that do not need medical attention unless they persist
or interfere with normal activities. These include
changes in menstrual period, itchy skin, nausea and
vomiting, and loss of appetite.
Other rare side effects may occur. Anyone who has
unusual symptoms after taking anticancer drugs should
contact the physician who prescribed the medication.

Interactions



black, tarry, or bloody stools



blood in the urine



diarrhea



fever or chills



cough or hoarseness



wheezing or shortness of breath



sores in the mouth or on the lips



unusual bleeding or bruising



swelling of the face



red ‘‘pinpoint’’ spots on the skin



redness, pain, or swelling at the point where an injectable anticancer drug is given



pain in the side or lower back



problems urinating or painful urination



dizziness or faintness



fast or irregular heartbeat

Anticholinergic drugs see Antiparkinson drugs

Other side effects do not need immediate care, but
should have medical attention. They are:

Anticlotting drugs see Anticoagulant and
antiplatelet drugs

GALE ENCYCLOPEDIA OF MEDICINE

Anticancer drugs may interact with a number of
other medicines. When this happens, the effects of one
or both of the drugs may change or the risk of side effects
may be greater. The health care provider should be aware
of all other prescription or non-prescription (over-thecounter) medicines a patient is taking. The primary care
provider should also be told if the patient has been treated
with radiation or has taken other anticancer drugs.
Resources
PERIODICALS

‘‘Technique Streamlines Search for Anticancer Drugs.’’
Cancer Weekly April 15, 2003: 62.

Samuel D. Uretsky, PharmD
Teresa G. Odle

275

Anticoagulant and antiplatelet drugs

I Anticoagulant
and antiplatelet
drugs

KEY TERMS
Anticoagulant—Drug used to prevent clot formation or to prevent a clot that has formed from enlarging. Anticoagulant drugs inhibit clot formation by
blocking the action of clotting factors or platelets.
Anticoagulant drugs fall into three groups: inhibitors of clotting factor synthesis, inhibitors of thrombin and antiplatelet drugs.

Definition
Anticoagulants are drugs used to prevent clot formation or to prevent a clot that has formed from enlarging. They inhibit clot formation by blocking the action
of clotting factors or platelets. Anticoagulant drugs fall
into three categories: inhibitors of clotting factor synthesis, inhibitors of thrombin and antiplatelet drugs.

Antiplatelet drug—Drug that inhibits platelets from
aggregating to form a plug. They are used to prevent
clotting and alter the natural course of atherosclerosis.
Atherosclerosis—Condition characterized by
deposits of fatty plaque in the arteries.

Purpose
Anticoagulant drugs reduce the ability of the blood
to form clots. Although blood clotting is essential to
prevent serious bleeding in the case of skin cuts, clots
inside the blood vessels block the flow of blood to major
organs and cause heart attacks and strokes. Although
these drugs are sometimes called blood thinners, they
do not actually thin the blood. Furthermore, this type
of medication will not dissolve clots that already have
formed, although the drug stops an existing clot from
worsening. However, another type of drug, used in
thrombolytic therapy, will dissolve existing clots.
Anticoagulant drugs are used for a number of conditions. For example, they may be given to prevent blood
clots from forming after the replacement of a heart valve
or to reduce the risk of a stroke or another heart attack
after a first heart attack. They are also used to reduce the
chance of blood clots forming during open heart surgery
or bypass surgery. Low doses of these drugs may be
given to prevent blood clots in patients who must stay in
bed for a long time after certain types of surgery.
Because anticoagulants affect the blood’s ability
to clot, they can increase the risk of severe bleeding
and heavy blood loss. It is thus essential to take these
drugs exactly as directed and to see a physician regularly as long as they are prescribed.

Description
Anticoagulant drugs, also called anticlotting drugs
or blood thinners, are available only with a physician’s
prescription. They come in tablet and injectable forms.
They fall into three groups:


Inhibitors of clotting factor synthesis. These anticoagulants inhibit the production of certain clotting
factors in the liver. One example is warfarin (brand
name: coumadin).



Inhibitors of thrombin. Thrombin inhibitors interfere
with blood clotting by blocking the activity of thrombin. They include heparin, lepirudin (Refludan).

276

Clot—A soft, semi-solid mass that forms when
blood gels.
Platelet—A small, disk-shaped body in the blood
that has an important role in blood clotting: they
form the initial plug at the rupture site of a blood
vessel.
Thrombin—Thrombin is a protein produced by the
body. It is a specific clotting factor that plays an
important role in the blood clotting process.
Thrombin inhibitor—Thrombin inhibitors are one
type of anticoagulant medication, used to help prevent formation of harmful blood clots in the body
by blocking the activity of thrombin.



Antiplatelet drugs. Antiplatelet drugs interact with
platelets, which is a type of blood cell, to block platelets from aggregating into harmful clots. They include:
aspirin, ticlopidine (Ticlid), clopidogrel (Plavix), tirofiban (Aggrastat), and eptifibatide (Integrilin).

Recommended dosage
The recommended dosage depends on the type of
anticoagulant drug and the medical condition for
which it is prescribed. The prescribing physician or
the pharmacist who filled the prescription can provide
information concerning the correct dosage. Usually,
the physician will adjust the dose after checking the
patient’s clotting time.
Anticoagulant drugs must be taken exactly as directed by the physician. Larger or more frequent doses
should not be taken, and the drug should also not be
taken for longer than prescribed. Taking too much of this
medication can cause severe bleeding. Anticoagulants
should also be taken on schedule. A record of each
dose should be kept as it is taken. If a dose is missed, it
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Persons who take anticoagulants should see a physician regularly while taking these drugs, particularly at
the beginning of therapy. The physician will order periodic blood tests to check the blood’s clotting ability. The
results of these tests will help the physician determine the
proper amount of medication to be taken each day.
Time is required for normal clotting ability to
return after anticoagulant treatment. During this period, patients must observe the same precautions they
observed while taking the drug. The length of time
needed for the blood to return to normal depends on
the type of anticoagulant drug that was taken. The
prescribing physician will advise as to how long the
precautions should be observed.
People who are taking anticoagulant drugs should
tell all physicians, dentists, pharmacists, and other
medical professionals who provide medical treatments
or services to them that they are taking such a medication. They should also carry identification stating that
they are using an anticoagulant drug.
Other prescription drugs or over-the-counter
medicine–especially aspirin–should be not be taken
without the prescribing physician being informed.
Because of the risk of heavy bleeding, anyone who
takes an anticoagulant drug must take care to avoid
injuries. Sports and other potentially hazardous activities should be avoided. Any falls, blows to the body or
head, or other injuries should be reported to a physician,
as internal bleeding may occur without any obvious
symptoms. Special care should be taken in shaving
and in brushing and flossing the teeth. Soft toothbrushes should be used and the flossing should be very
gentle. Electric razors should be used instead of a blade.
Alcohol can change the way anticoagulant drugs
affect the body. Anyone who takes this medicine
should not have more than one to two drinks at any
time and should not drink alcohol every day.
Special conditions
People with specific medical conditions or who are
taking certain other medicines can have problems if
they take anticoagulant drugs. Before taking these
GALE ENCYCLOPEDIA OF MEDICINE

drugs, the prescribing physician should be informed
about any of these conditions:
ALLERGIES. Anyone who has had unusual reactions to anticoagulants in the past should let his or
her physician know before taking the drugs again. The
physician should also be told about any allergies to
beef, pork, or other foods; dyes; preservatives; or other
substances.
PREGNANCY. Anticoagulants may cause many
serious problems if taken during pregnancy. Birth
defects, severe bleeding in the fetus, and other problems that affect the physical or mental development
of the fetus or newborn are possible. The mother may
also experience severe bleeding if she takes anticoagulants during pregnancy, during delivery, or even
shortly after delivery. Women should not take start
taking anticoagulants during pregnancy and should not
become pregnant while taking it. Any woman who
becomes pregnant or suspects that she has become pregnant while taking an anticoagulant should check with
her physician immediately.
BREASTFEEDING. Some anticoagulant drugs may
pass into breast milk. Blood tests can be done on
nursing babies to see whether the drug is causing any
problems. If it is, other medication may be prescribed
to counteract the effects of the anticoagulant drug.
OTHER MEDICAL CONDITIONS. Before using anticoagulant drugs, people should inform their physician
about any medical problems they have. They should
also let the physician who prescribed the medicine
know if they are being treated by any other medical
physician or dentist. In addition, people who will be
taking anticoagulant drugs should let their physician
know if they have recently had any of the following:


fever lasting more than one to two days



severe or continuing diarrhea



childbirth



heavy or unusual menstrual bleeding



insertion of an intrauterine contraceptive device
(IUD)



falls, injuries, or blows to the body or head



any type of surgery, including dental surgery



spinal anesthesia



radiation treatment

USE OF CERTAIN FOODS AND MEDICINES. Many
foods and drugs may affect the way the anticoagulant
drugs work or may increase the risk of side effects.

277

Anticoagulant and antiplatelet drugs

should be taken as soon as possible followed by the
regular dose schedule. However, a patient who forgets
to take a missed dose until the next day should not take
the missed dose at all and should not double the next
dose, as this could lead to bleeding. A record of all
missed doses should be kept for the prescribing physician who should be informed at the scheduled visits.

Anticonvulsant drugs

Side effects
The most common minor side effects are bloating or
gas. These problems usually go away as the body adjusts
to the drug and do not require medical treatment.
More serious side effects may occur, especially if
excessive anticoagulant is taken. If any of the following side effects occur, a physician should be notified
immediately:


bleeding gums



sores or white spots in the mouth or throat



unusual bruises or purplish areas on the skin



unexplained nosebleeds



unusually heavy bleeding or oozing from wounds



unexpected or unusually menstrual bleeding



blood in the urine



cloudy or dark urine



painful or difficult urination or sudden decrease in
amount of urine



black, tarry, or bloody stools



coughing up blood



vomiting blood or something that looks like coffee
grounds



constipation



pain or swelling in the stomach or abdomen



back pain



stiff, swollen, or painful joints



painful, bluish or purplish fingers or toes



puffy or swollen eyelids, face, feet, or lower legs



changes in the color of the face



skin rash, itching, or hives



yellow eyes or skin



severe or continuing headache



sore throat and fever, with or without chills



breathing problems or wheezing



tightness in the chest



dizziness



unusual tiredness or weakness



weight gain.

In addition, patients taking anticoagulant drugs
should check with their physicians as soon as possible
if any of these side effects occur:


nausea or vomiting

278



diarrhea



stomach pain or cramps.

Other side effects may occur. Anyone who has
unusual symptoms while taking anticoagulant drugs
should get in touch with his or her physician.

Interactions
Anticoagulants may interact with many other medications. When this happens, the effects of one or both
of the drugs may change or the risk of side effects may
be increased. Anyone who takes anticoagulants should
inform the prescribing physician about other prescription
or nonprescription (over-the-counter medicines) he or she
is taking–even aspirin, laxatives, vitamins, and antacids.
Diet also affects the way anticoagulant drugs work
in the body. A normal, balanced diet should be followed
every day while taking such medication. No dietary
changes should be made without informing first the
prescribing physician, who should also be told of any
illness or other condition interfering with the ability to
eat normally. Diet is a very important consideration
because the amount of vitamin K in the body affects
how anticoagulant drugs work. Dicoumarol and warfarin act by reducing the effects of vitamin K. Vitamin K
is found in meats, dairy products, leafy, green vegetables, and some multiple vitamins and nutritional supplements. For the drugs to work properly, it is best to have
the same amount of vitamin K in the body all the time.
Foods containing vitamin K in the diet should not be
increased or decreased without consulting with the prescribing physician. If the patient takes vitamin supplements, he should check the label to see if it contains
vitamin K. Because vitamin K is also produced by intestinal bacteria, a severe case of diarrhea or the use of
laxatives may also alter a person’s vitamin K levels.
Nancy Ross-Flanigan

I Anticonvulsant drugs
Definition
Anticonvulsant drugs are medicines used to prevent or treat convulsions (seizures).

Purpose
Anticonvulsant drugs are used to control seizures
in people with epilepsy. Epilepsy is not a single disease—it is a set of symptoms that may have different
GALE ENCYCLOPEDIA OF MEDICINE

Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Epilepsy—A brain disorder with symptoms that
include seizures.
Glaucoma—A condition in which pressure in the
eye is abnormally high. If not treated, glaucoma
may lead to blindness.
Porphyria—A disorder in which porphyrins build
up in the blood and urine.
Porphyrin—A type of pigment found in living
things, such as chlorophyll which makes plants
green or hemoglobin which makes blood red.
Seizure—A sudden attack, spasm, or convulsion.
Systemic lupus erythematosus (SLE)—A chronic
disease with many symptoms, including weakness,
fatigue, joint pain, sores on the skin, and problems
with the kidneys, spleen, and other organs.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug to which he or she has
become dependent.

causes in different people. The common thread is an
imbalance in the brain’s electrical activity. This imbalance causes seizures that may affect part or all of the
body and may or may not cause a loss of consciousness. Anticonvulsant drugs act on the brain to reduce
the frequency and severity of seizures.
Some cases of epilepsy are brought on by head
injuries, brain tumors or infections, or metabolic problems such as low blood sugar. But in some people
with epilepsy, the cause is not clear.
Anticonvulsant drugs are an important part of the
treatment program for epilepsy. Different kinds of
drugs may be prescribed for different types of seizures.
In addition to taking medicine, patients with epilepsy
should get enough rest, avoid stress, and practice good
health habits.
Some physicians believe that giving the drugs to
children with epilepsy may prevent the condition from
getting worse in later life. However, others say the
effects are the same, whether treatment is started
early or later in life. Determining when treatment
begins depends on the physician and his assessment
of the patient’s symptoms.
GALE ENCYCLOPEDIA OF MEDICINE

Physicians also prescribe certain anticonvulsant
drugs for other conditions, including bipolar disorder
and migraine headaches.

Description
Anticonvulsant drugs may be divided into several
classes. The hydantoins include pheytoin (Dilantin) and
mephenytoin (Mesantoin.) Ther succimides include
ethosuximide (Zarontin) and methsuccimide (Celontin.)
The benzodiazepines, which are better known for their
use as tranquilizers and sedatives, include clonazepam
(Klonopin), clorazepate (Tranxene) and diazepam
(Valium.) There are also a large number of other drugs
which are not related to larger groups. These include
carbamazepine (Tegretol), valproic acid (Depakote,
Depakene) gabapentin (Neurontin), topiramate
(Topamax), felbamate (Felbatol) and several others.
Phenobarbital has been used as an anticonvulsant, and
is still useful for some patients. The drugs are available
only with a physician’s prescription and come in tablet,
capsule, liquid, and ‘‘sprinkle’’ forms.

Recommended dosage
The recommended dosage depends on the type of
anticonvulsant, its strength, and the type of seizures
for which it is being taken. Check with the physician
who prescribed the drug or the pharmacist who filled
the prescription for the correct dosage.
Do not stop taking this medicine suddenly after
taking it for several weeks or more. Gradually tapering
the dose may reduce the chance of withdrawal effects.
Do not change brands or dosage forms of this
medicine without checking with a pharmacist or physician. If a prescription refill does not look like the
original medicine, check with the pharmacist who
filled the prescription.

Precautions
Patients on anticonvulsant drugs should see a
physician regularly while on therapy, especially during
the first few months. The physician will check to make
sure the medicine is working as it should and will note
unwanted side effects. The physician may also need to
adjust the dosage during this period.
Valproic acid can cause serious liver damage,
especially in the first 6 months of treatment. Children
are particularly at risk, but anyone taking this medicine should see their physician regularly for tests of
liver function and should be alert to symptoms of liver
damage, such as yellow skin and eyes, facial swelling,
279

Anticonvulsant drugs

KEY TERMS

Anticonvulsant drugs

loss of appetite, general feeling of illness, loss of appetite, and vomiting. If liver problems are suspected, call
a physician immediately.
Felbatol has caused serious liver damage and
aplastic anemia, a condition in which the bone marrow stops producing blood cells. Patients taking this
drug should have regular blood counts, and should
stop taking the drug if there are too few red blood
cells.
While taking anticonvulsant drugs, do not start or
stop taking any other medicines without checking with
a physician. The other medicines may affect the way
the anticonvulsant medicine works.
Because anticonvulsant drugs work on the central
nervous system, they may add to the effects of alcohol
and other drugs that slow down the central nervous
system, such as antihistamines, cold medicine, allergy
medicine, sleep aids, other medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants.
Anyone taking anticonvulsant drugs should check with
his or her physician before drinking alcohol or taking
any medicines that slow the central nervous system.
Anticonvulsant drugs may interact with medicines
used during surgery, dental procedures, or emergency
treatment. These interactions could increase the
chance of side effects. Anyone who is taking anticonvulsant drugs should be sure to tell the health care
professional in charge before having any surgical or
dental procedures or receiving emergency treatment.
Some people feel drowsy, dizzy, lightheaded, or
less alert when using these drugs, especially when they
first begin taking them or when their dosage is
increased. Anyone who takes anticonvulsant drugs
should not drive, use machines or do anything else
that might be dangerous until they have found out
how the drugs affect them.
Anticonvulsant drugs may affect the results of
certain medical tests. Before having medical tests, people who take anticonvulsant drugs should make sure
that the medical professional in charge knows what
they are taking.
Children may be more likely to have certain side
effects from anticonvulsant drugs, such as behavior
changes; tender, bleeding, or swollen gums; enlarged
facial features; and excessive hair growth. Problems
with the gums may be prevented by regularly brushing
and flossing, massaging the gums, and having the teeth
cleaned every 3 months whether the patient is a child
or an adult.
Children who take high doses of this medicine for
a long time may have problems in school.
280

Older people may be more sensitive to the effects
of anticonvulsant drugs. This may increase the chance
of side effects and overdoses.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take anticonvulsant drugs. Before taking these
drugs, be sure to let the physician know about any of
these conditions:
ALLERGIES. Anyone who has had unusual reactions to anticonvulsant drugs or to tricyclic antidepressants such as imipramine (Tofranil) or desipramine
(Norpramin) in the past should let his or her physician
know before taking the drugs again. The physician
should also be told about any allergies to foods,
dyes, preservatives, or other substances.
PREGNANCY. Some anticonvulsant drugs taken
during pregnancy may cause bleeding problems in the
mother during delivery and in the baby after delivery.
This problem can be avoided by giving vitamin K to the
mother during delivery and to the baby after birth.

Pregnancy may affect the way the body absorbs
anticonvulsant drugs. Women who are prone to seizures may have more seizures during pregnancy, even
though they are taking their medicine regularly. If this
happens, they should check with their physicians
about whether the dose needs to be increased.
BREASTFEEDING. Some anticonvulsant drugs pass
into breast milk and may cause unwanted effects in babies
whose mothers take the medicine. Women who are
breastfeeding should check with their physicians about
the benefits and risks of using anticonvulsant drugs.
DIABETES. Anticonvulsant drugs may affect blood
sugar levels. Patients with diabetes who notice changes
in the results of their urine or blood tests should check
with their physicians.
OTHER MEDICAL CONDITIONS. Before using anticonvulsant drugs, people with any of these medical
problems should make sure their physicians are
aware of their conditions:


liver disease



kidney disease



thyroid disease



heart or blood vessel disease



blood disease



brain disease



problems with urination



current or past alcohol abuse
GALE ENCYCLOPEDIA OF MEDICINE

behavior problems



diabetes mellitus



glaucoma



porphyria



systemic lupus erythematosus



fever higher than 101 8F (38.3 8C) for more than
24 hours

USE OF CERTAIN MEDICINES. Taking anticonvulsant drugs with certain other drugs may affect the
way the drugs work or may increase the chance of
side effects.

Side effects
The most common side effects are constipation,
mild nausea or vomiting, and mild dizziness, drowsiness, or lightheadedness. These problems usually go
away as the body adjusts to the drug and do not
require medical treatment. Less common side effects,
such as diarrhea, sleep problems, aching joints or muscles, increased sensitivity to sunlight, increased sweating, hair loss, enlargement of facial features, excessive
hair growth, muscle twitching, and breast enlargement
in males also may occur and do not need medical
attention unless they persist or are troublesome.
Other side effects may need medical attention. If
any of these side effects occur, check with a physician
as soon as possible:

Interactions
Some anticonvulsant drugs should not be taken
within two to three hours of taking antacids or medicine for diarrhea. These medicines may make the
anticonvulsant drugs less effective. Ask the pharmacist or physician for more information.
Birth control pills may not work properly when
anticonvulsant drugs are being taken. To prevent
pregnancy, ask the physician or pharmacist if additional methods of birth control should be used while
taking anticonvulsant drugs.
Anticonvulsant drugs may interact with many
other medicines. When this happens, the effects of
one or both of the drugs may change or the risk of
side effects may be greater. Anyone who takes anticonvulsant drugs should let the physician know all
other medicines he or she is taking. Among the
drugs that may interact with certain anticonvulsant
drugs are:


airway opening drugs (bronchodilators) such as aminophylline, theophylline (Theo-Dur and other brands),
and oxtriphylline (Choledyl and other brands)



medicines that contain calcium, such as antacids and
calcium supplements



blood thinning drugs



caffeine



antibiotics such as clarithromycin (Biaxin), erythromycins, and sulfonamides (sulfa drugs)



clumsiness or unsteadiness



disulfiram (Antabuse), used to treat alcohol abuse



slurred speech or stuttering



fluoxetine (Prozac)



trembling





unusual excitement, irritability, or nervousness



uncontrolled eye movements

monoamine oxidase inhibitors (MAO inhibitors)
such as phenelzine (Nardil) or tranylcypromine
(Parnate), used to treat conditions including depression and Parkinson’s disease



blurred or double vision





mood or mental changes

tricyclic antidepressants such as imipramine (Tofranil)
or desipramine (Norpramin)



confusion



corticosteroids



increase in seizures



acetaminophen (Tylenol)



bleeding, tender, or swollen gums



aspirin



skin rash or itching



female hormones (estrogens)



enlarged glands in neck or armpits



male hormones (androgens)

muscle weakness or pain





cimetidine (Tagamet)

fever





central nervous system (CNS) depressants such as medicine for allergies, colds, hay fever, and asthma; sedatives;
tranquilizers; prescription pain medicine; muscle relaxants; medicine for seizures; sleep aids; barbiturates; and
anesthetics

Other side effects are possible. Anyone who has
unusual symptoms after taking anticonvulsant drugs
should get in touch with his or her physician.
GALE ENCYCLOPEDIA OF MEDICINE

281

Anticonvulsant drugs



Antidepressant drugs



alcohol



other anticonvulsant drugs

KEY TERMS

The list above does not include every drug that
may interact with anticonvulsant drugs. Be sure to
check with a physician or pharmacist before combining anticonvulsant drugs with any other prescription
or nonprescription (over-the-counter) medicine.

Cognitive behavioral therapy—A type of psychotherapy in which people learn to recognize
and change negative and self-defeating patterns of
thinking and behavior.
Depression—A mental condition in which people
feel extremely sad and lose interest in life. People
with depression also may have sleep problems and
loss of appetite and may have trouble concentrating and carrying out everyday activities.
Pregnancy category— A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B:
Animal studies indicate no fetal risk, but no
human studies; or adverse effects in animals, but
not in well-controlled human studies. Category C:
No adequate human or animal studies; or adverse
fetal effects in animal studies, but no available
human data. Category D: Evidence of fetal risk,
but benefits outweigh risks. Category X: Evidence
of fetal risk. Risks outweigh any benefits.

Resources
PERIODICALS

Reynolds, E.H. ‘‘Do Anticonvulsant Drugs Alter the
Natural Course of Epilepsy? Treatment Should Be
Started as Early as Possible.’’ British Medical Journal
310 (January 21, 1995): 176.
ORGANIZATIONS

American Epilepsy Society. 638 Prospect Avenue, Hartford,
CT 06105. (203) 232-4825.
Epilepsy Foundation of America. 4351 Garden City Drive,
#406, Landover, MD 20785. (800) 332-1000.
National Institute of Neurological Disorders and Stroke.
P.O. Box 5801, Bethesda, MD 20824. (301) 496-5751.

Nancy Ross-Flanigan

Description

I Antidepressant drugs
Definition
Antidepressant drugs are medicines that relieve
symptoms of depressive disorders.

Purpose
Depressive disorders may either be unipolar
(depression alone) or bipolar (depression alternating
with periods of extreme excitation). The formal diagnosis requires a cluster of symptoms, lasting at least
two weeks. These symptoms include, but are not limited to, mood changes, insomnia or hypersomnia, and
diminished interest in daily activities. The symptoms
are not caused by any medical condition, drug side
effect, or adverse life event. The condition is severe
enough to cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
Secondary depression, or depression caused by
unfavorable life events, is normally self limiting, and
may best be treated with cognitive/behavioral therapy
rather than drugs.
282

Antidepressant agents act by increasing the levels
of excitatory neurostransmitters, or nerve cell chemicals
that act as messengers in the brain’s nervous system. In
2003, a report showed that in addition to treating
depression, use of antidepressant drugs may protect
the brain from damage depressive episodes cause to
the hippocampus, the area of the brain involved in
learning and memory. Antidepressant drugs may be
prescribed as a first-line treatment for depression, or
in conjunction with other methods of controlling
depression, such as behavioral therapy and exercise.
The main types of antidepressant drugs in use
today are listed below, though the drugs available
change frequently. For example, in mid-2003, the
manufacturer of Wellbutrin released Wellbutrin XL,
the only once-daily norepinephrine and dopamine
reuptake inhibitor for treating depression in adults.


tricyclic antidepressants, such as amitriptyline (Elavil),
imipramine (Tofranil), nortriptyline (Pamelor)



selective serotonin reuptake inhibitors (SSRIs or
serotonin boosters), such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)



monoamine oxidase inhibitors (MAO inhibitors), such
as phenelzine (Nardil), and tranylcypromine (Parnate)
GALE ENCYCLOPEDIA OF MEDICINE

tetracyclic compounds and atypical antidepressants
which do not fall into any of the above categories

Selective serotonin reuptake inhibitors maintain
levels of the excitatory neurohormone serotonin in the
brain. They do not alter levels of norepinephrine. These
have become the drugs of choice for a variety of psychiatric disorders, primarily because of their low incidence of severe side effects as compared with other drugs
in this therapeutic class. SSRIs show similar actions and
side effect profiles, but may vary in duration of action.
Tricyclic compounds, identified by their chemical
structure containing three carbon rings, are an older
class of antidepressants. Although generally effective,
they have a high incidence of anticholinergic effects,
notably dry mouth and dry eyes, which can cause
discomfort. They also cause cardiac arrythmias.
Because tricyclics act on both serotonin and norepinephrine, they may have some value in treatment of
patients who fail to respond to SSRIs. Drugs in this
class often are available at low prices, which may be
significant when cost is a major factor in treatment.
They also have been found useful in control of some
neurologic pain syndromes.
Tricyclic antidepressants are similar, but may vary
in severity of side effects, most notably the degree of
sedation and the extent of the anticholinergic effects.
Tetracyclic compounds and atypical antidepressants are chemically distinct from both the major
groups and each other. Although maprotilene (no
brand name, marketed in generic form only) and mirtazepine (Remeron) are similar in chemical structures,
they differ in their balance of activity on serotonine
and norepinephrine levels.
Monoamine oxidase inhibitors (phenelzine
[Nardil], tranylcypromine [Parnate]) have largely
been supplanted in therapy because of their high risk
of severe adverse effects, most notably severe hypertension. They act by inhibiting the enzyme monoamine
oxidase, which is responsible for the metabolism of the
stimulatory neurohormones norepinephrine, epinephrine, dopamine, and serotonin. The MAOIs are
normally reserved for patients who are resistant to
safer drugs. Two drugs, eldepryl (Carbex, used in
treatment of Parkinson’s disease) and the herb,
St. John’s wort, have some action against monoamine oxidase B, and have shown some value as antidepressants. They do not share the same risks as the
non-selective MAO inhibitors.
All antidepressant agents, regardless of their
structure, have a slow onset of action, typically three
to five weeks. Although adverse effects may be seen as
early as the first dose, significant therapeutic
GALE ENCYCLOPEDIA OF MEDICINE

improvement is always delayed. Similarly, the effects
of antidepressants will continue for a similar length of
time after the drugs have been discontinued.

Recommended dosage
Dose varies with the specific drug and patient.
Specialized references or a physician should be consulted.

Precautions
Antidepressants have many significant cautions
and adverse effects. Although a few are listed here,
specific references should be consulted for more complete information.
SSRIs. The most common side effect of SSRIs is
excitation and insomnia. Excitation has been reported
in over 20% of patients, and insomnia in 33%.
Significant weight loss has been frequently reported,
but most commonly in patients who are already
underweight. A 2003 report showed that SSRIs also
increase the risk of upper gastrointestinal tract bleeding. SSRIs may cause some sedation, and patients
should be cautioned not to perform tasks requiring
alertness until they have evaluated the effects of these
drugs. SSRIs are pregnancy category C drugs. In 2003,
a new report demonstrated that late-term (third trimester) use of these drugs could cause neurological symptoms in newborns, including tremor, restlessness and
rigidity. Most SSRIs are excreted in breast milk, and
there have been anecdotal reports of drowsiness in
infants whose mothers were taking SSRIs while
breastfeeding.
Most notably, a joint panel of the U.S. Food and
Drug Administration (FDA) issued strong warnings
to parents and physicians in 2004 about the risk of
suicidal behavior in children and adolescents taking
SSRIs.
Tricyclic antidepressants. Amoxepine (not marketed by brand, generic available), although a tricyclic
antidepressant rather than a neuroleptic (major tranquilizer), displays some of the more serious effects of
the neuroleptics, including tardive dyskinesias (drug
induced involuntary movements) and neuroleptic
malignant syndrome, a potentially fatal syndrome
with symptoms including high fever, altered mental
status, irregular pulse or blood pressure, and changes
in heart rate. These adverse effects have not been
reported with other tricyclic antidepressants.
The most common adverse effects of tricyclic antidepressants are sedation and the anticholinergic
effects, such as dry mouth, dry eyes, and difficult
urination. Alterations in heartbeat also are common,
283

Antidepressant drugs



Antidepressant drugs, SSRI

and may progress to congestive heart failure, stroke,
and sudden death.
Tricyclic antidepressants are in pregnancy categories C or D, although there have been no formal
studies of the drugs on fetal development. There are no
studies of effects on newborns, but some anecdotal
reports of malformations have resulted from animal
studies. The drugs are excreted in breast milk.
Monoamine oxidase inhibitors. The greatest risk
associated with these drugs is a hypertensive crisis
which may be fatal and most often occurs when the
drugs are taken with interacting foods or drugs. More
common adverse reactions may include low blood
pressure and slowing of heartbeat. Sedation and gastrointestinal disturbances also are common. MAOIs
are in pregnancy category C. Safety in breast feeding
has not been established.
Tetracyclics and atypicals. Because these drugs
are individual, there are no group patterns of adverse
reactions. Specific references should be consulted.

Interactions
The antidepressants have many drug interactions,
some severe. Although a few are listed here, specific
references should be consulted for more complete
information.
SSRIs should not be administered with MAOIs.
A wash-out period of about four weeks should be
allowed before switching from one class of drugs to
the other, five weeks if switching from fluoxetine
(Prozac) to an MAOI.
MAOIs have many interactions, however the best
known are those with foods containing the amino acid
tyramine. These include aged cheese, chianti wine, and
many others. Patients and providers should review the
MAOI diet restrictions before using or prescribing
these drugs. Because of the severity of MAOI interactions, all additions to the patient’s drug regimen
should be reviewed with care.
Tricyclic compounds have many interactions, and
specialized references should be consulted.
Specifically, it is best to avoid other drugs with anticholinergic effects. Tricyclics should not be taken with
the antibiotics grepafloxacin and sprafloxacin, since
the combination may cause serious heart arrythmias.
Tricyclic compounds should not be taken with the
gastric acid inhibitor cimetidine (Tagamet), since this
increases the blood levels of the tricyclic compound.
Other acid inhibiting drugs do not share this
interaction.
284

SSRIs interact with a number of other drugs that
act on the central nervous system. Care should be used
in combining these drugs with major or minor tranquilizers, or with anti-epileptic agents such as phenytoin (Dilantin) or carbamazepine (Tegretol). In 2003,
one of the biggest concerns regarding new prescriptions for tricyclic antidepressants was data concerning
overdoses from these drugs. Information in Great
Britain showed that this class of antidepressants was
responsible for more than 90% of all deaths from
antidepressant overdose. Physicians were being
advised to prescribe SSRIs in new patients, but not
to change the course of those who had taken tricyclics
for years with success.
Resources
PERIODICALS

‘‘Antidepressant Drugs May Protect Brain from Damage.’’
Mental Health Weekly Digest (August 18, 2003): 2.
‘‘FDA Approves Once-daily Supplement.’’ Biotech Week
(September 24, 2003): 6.
‘‘FDA Panel Urges Stronger Warnings of Child Suicide.’’
SCRIP World Pharmaceutical News (February 6,
2004): 24.
‘‘GPs Told Not to Prescribe Tricyclics.’’ Pulse (October 13,
2003): 1.
‘‘Late-term Exposure to SSRIs May Cause Neurological
Symptoms in Babies.’’ Drug Week (August 8, 2003):
255.
‘‘SSRIs Increase the Risk of Upper GI Bleeding.’’
Psychiatric Times (July 1, 2003): 75.

Samuel D. Uretsky, PharmD
Teresa G. Odle

I Antidepressant drugs, SSRI
Definition
Purpose
SSRIs are prescribed primarily to treat mental
depression. Because they are as effective as other
types of antidepressants and have less serious side
effects, SSRIs have become the most commonly prescribed antidepressants for all age groups, including
children and adolescents.
In addition to treating depression, some SSRIs
have been approved by the U.S. Food and Drug
Administration (FDA) for the treatment of other disorders including:
GALE ENCYCLOPEDIA OF MEDICINE

obsessive-compulsive disorder (OCD)



generalized anxiety disorder



panic disorder



social anxiety disorder or social phobia



premenstrual dysphoric disorder (PMDD)
premenstrual syndrome (PMS)



post-traumatic stress disorder (PTSD)



bulimia nervosa, an eating disorder.

KEY TERMS
Citalopram hydrobromide—Celexa; a SSRI that is
highly specific for serotonin reuptake.
Dopamine—A neurotransmitter and the precursor
of norepinephrine.

or

Escitalopram oxalate—Lexapro; a SSRI that is very
similar to Celexa but contains only the active chemical form.
Fluoxetine—Prozac; the first SSRI; marketed as
Sarafem for treating PMDD.

SSRIs often are prescribed for other ‘‘off-label’’
uses including:


various mental disorders including schizophrenia



mania



menopause-related symptoms such as hot flashes



geriatric depression



loss of mental abilities in the elderly



nicotine withdrawal



alcoholism



premature ejaculation

Fluvoxamine—Luvox; a SSRI that is used to treat
obsessive-compulsive disorder as well as other
conditions.
Monoamine oxidase inhibitor (MAOI)—An older
class of antidepressants.
Neurotransmitter—A substance that helps transmit
impulses between two nerve cells or between a
nerve cell and a muscle.
Norepinephrine—A hormone released by nerve
cells and the adrenal medulla that causes constriction of blood vessels.
Obsessive-compulsive disorder (OCD)—An anxiety disorder characterized by obsessions, such as
recurring thoughts or impulses, and compulsions,
such as repetitive behaviors.
Off-label use—A drug that is prescribed for uses,
periods of time, or at dosages that are not FDAapproved.

The advantages of SSRIs over other types of antidepressants include:


Most SSRIs can be taken in one daily dose as compared with three to six daily pills.



Because they lessen cravings for carbohydrates,
SSRIs usually do not cause weight gain.



Since SSRIs do not appear to affect the cardiovascular system, they can be prescribed for people with
high blood pressure or heart conditions.



Paroxetine hydrochloride—Paxil; a SSRI that is
used to treat mental depression, OCD, and various
other disorders.

Since SSRIs are not particularly dangerous even in high
doses and are unlikely to cause permanent damage if
misused, they may be prescribed for suicidal adults.

Premenstrual dysphoric disorder (PMDD)—
Premenstrual syndrome (PMS); symptoms including back and abdominal pain, nervousness and
irritability, headache, and breast tenderness that
occur the week before menstruation.
Serotonin—5-Hydroxytryptamine; a substance
that occurs throughout the body with numerous
effects including neurotransmission.

SSRIs are mood enhancers only in depressed individuals. They have little effect on people who are not
clinically depressed. However some experts believe
that SSRIs are over-prescribed and should be reserved
for those with major disabling depression.

Serotonin syndrome—A group of symptoms caused
by severely elevated serotonin levels in the body.

Description
Types of SSRIs

Sertraline—Zoloft; a SSRI that is used to treat mental depression and a variety of other disorders.

As of 2005, six brand-name SSRIs and generic
equivalents were available in the United States:




Celexa (citalopram hydrobromide) for treating
depression
Lexapro (escitalopram oxalate) for treating depression and generalized anxiety disorder

GALE ENCYCLOPEDIA OF MEDICINE



Luvox (fluvoxamine) for treating OCD



Paxil (paroxetine hydrochloride) for treating
depression, generalized anxiety disorder, OCD,
285

Antidepressant drugs, SSRI



Antidepressant drugs, SSRI

panic disorder, social anxiety disorder, PMDD, and
PTSD


Prozac and Prozac Weekly (fluoxetine) for treating
depression, OCD, and bulimia nervosa; marketed as
Sarafem for treating PMDD



Zoloft (sertraline) for treating depression, OCD,
panic disorder, social anxiety disorder, PMDD, and
PTSD.

When Prozac first became available in 1988, it was
hailed as a new wonder drug and quickly became the most
popular antidepressant ever prescribed. Many millions
of Americans have taken Prozac and more than 70%
of them claim to have benefited from it. Within a few
years other SSRIs became available and, by 2000, Zoloft
prescriptions outnumbered those for Prozac.
Lexapro is the newest SSRI. Celexa and Lexapro
are very similar, with chemical structures unrelated to
other SSRIs. Celexa is a mixture of two isomers—
forms of the same chemical—whereas Lexapro is the
active isomer alone. They appear to be highly selective
for serotonin, only minimally inhibiting the reuptake
of the neurotransmitters norepinephrine and dopamine. Paxil is structurally unrelated to other SSRIs
and is more selective for serotonin than Luvox,
Prozac, or Zoloft, but less selective than Celexa and
Lexapro. Paxil becomes distributed widely throughout body tissues and the CNS, with only 1% remaining in the circulatory system.
Mode of action
Mental depression is believed to be related to the
low activity of one or more neurotransmitters in the
brain—the chemical messengers that cross the gap or
synapse between nerve cells. Although it is not understood exactly how most SSRIs work, they are designed
to increase the level of serotonin in the brain. This can
reduce the symptoms of depression and other psychological disorders.
Serotonin is released by nerve cells and then—in a
process called reuptake—is reabsorbed by the cells to
be used again. SSRIs interfere with reuptake by blocking the serotonin reuptake sites on the surfaces of
nerve cells, thereby making more serotonin available
for brain activity. Paxil inhibits the transporter molecule that moves serotonin back into the cell. SSRIs are
said to selectively interfere with the reuptake of serotonin, without affecting the uptake or activities of
other neurotransmitters. In contrast, older antidepressants such as tricyclic antidepressants and monoamine
oxidase inhibitors (MAOIs) affect numerous neurotransmitters, brain cell receptors, and brain processes,
increasing the likelihood of serious side effects.
286

However it is becoming clear that the serotonin
neurotransmitter system is far more complex and widespread throughout the body than was thought initially.
Although serotonin receptors are particularly common
in areas of the brain that control emotion, it is known
now that there are at least six different types of serotonin
receptors that send different signals to different parts of
the brain. Serotonin also appears to affect other neurotransmitter systems—including dopamine—to at least
some extent. Thus increasing the levels of serotonin may
not be the only reason why SSRIs relieve depression.
Effectiveness
SSRIs are not effective for treating anxiety or
depression in 20–40% of patients. However some
research suggests that the use of SSRIs in the early stages
of depression can prevent major depressive disorders.
Although different SSRIs appear to be equally
effective, individuals respond differently to different
SSRIs and side effects may vary. Thus finding the best
SSRI for an individual may be a matter of trial-anderror. It usually takes two to four weeks after starting an
SSRI before symptoms begin to improve. Luvox may
take one to two months for noticeable improvement.
Paxil may take as long as several months, although
sleeping often improves within one or two weeks of
beginning the medication. If there is no response after
a few weeks or if side effects occur, the patient may be
switched to another SSRI. Prozac is the most commonly
prescribed SSRI for children, in part because it is available in liquid form that is easier to swallow.
Although Luvox is the only SSRI that is FDAapproved for use in children—and only for obsessivecompulsive behavior—thousands of young people
have been treated with SSRIs for:


depression



anxiety



OCD



panic



attention deficit/hyperactivity disorder (ADHD)

A 2004 study found that among depressed adolescents, 60% improved with Prozac alone, whereas 75%
reported improvement with Prozac combined with
cognitive behavioral therapy.
SSRIs sometimes are prescribed to relieve depression accompanying alcoholism. A recent study found
that, although type A alcoholics responded to Zoloft
in conjunction with a 12-step individual therapy program, type B alcoholics—those with the most severe
GALE ENCYCLOPEDIA OF MEDICINE



Recommended dosage
Usually SSRIs are started with a low dosage that
may be gradually increased. In older adults SSRIs
remain in the body longer than in younger adults.
The blood levels of Paxil can be 70–80% higher in
the elderly as compared with younger patients.
Therefore lower doses usually are prescribed for
older people. Older patients with other medical conditions or who are taking many different drugs also
may need smaller or less frequent doses. The dosage
of an SSRI also varies according to the individual
and the condition that is being treated. SSRIs may be
taken with or without food, on a full or empty
stomach. However taking SSRIs with food or drink
may lessen side effects such as stomach upset or
nausea.
Celexa is supplied as tablets or as an oral solution
equivalent to 2 mg per ml (0.03 oz.), taken once per
day in the morning or evening:


adults: 20 mg per day, increasing to 40 mg if necessary, to a maximum of 60 mg per day



older adults: 20 mg per day to a maximum of 40 mg

Lexapro is supplied as 5-, 10-, or 20-mg tablets or
as a 1 mg per ml (0.03 oz.) liquid. The recommended
dose is 10 mg per day, with a possible increase to 20 mg
per day after at least one week.
Average dosages of Luvox for treating OCD and
depression are:






adults: one 50-mg tablet at bedtime; may be
increased up to a maximum of 300 mg daily; dosages
of more than 100 mg per day should be divided into
two doses, one taken in the evening and one in the
morning
children aged 8–17: initially one 25-mg tablet at
bedtime; may be gradually increased by 25 mg
per day every four to seven days, up to a maximum of 200 mg per day; daily dosages of more
than 50 mg should be divided into two daily
doses.

older adults: 10 mg (5 ml, 0.15 oz.) of oral suspension
or a 10-mg tablet daily, increased to a maximum of
40 mg (20 ml, 0.6 oz.); one 12.5-mg extended-release
tablet daily, increased to a maximum of 50 mg

Because of its sedating effect, Paxil may be taken
in the evening rather than in the morning as usually
recommended. Oral suspensions need to be shaken
well before measuring with a small measuring cup or
measuring spoon. Extended-release tablets should be
swallowed whole, not broken or chewed. Dosages may
be different for treating disorders other than
depression.
Typical dosages of Prozac are:


one 10–20-mg daily capsule or solution taken in the
morning; increased up to as much as 40 mg daily if
there is no improvement in one month, up to an
80-mg maximum



one 90-mg capsule per week of Prozac Weekly once
the depression is under control



one 20-mg capsule of Sarafem per day, taken in the
morning, every day or for only 14 days of a menstrual cycle; maximum of 80 mg per day; Sarafem is
supplied in seven-day blister packs to help keep track
of the days



children: initially one 5–10-mg capsule or solution
per day.

Zoloft is available as capsules, oral solutions, or
tablets:


adults: 50 mg daily, taken in the morning or evening,
up to a maximum of 200 mg daily for severely
depressed individuals



older adults: 12.5–25 mg per day, taken in the morning or evening; may be increased gradually



for treating OCD in children aged 6–12: 25 mg per
day, taken in the morning or evening; may be
increased gradually to a maximum of 200 mg per day



children aged 13–17: initially 50 mg per day, in the
morning or evening, may be increased gradually to a
maximum of 200 mg per day.

Average doses of Paxil for treating depression are:

Zoloft oral concentrate should be mixed with 4 oz
(133 ml) of water, ginger ale, lemon-lime soda, lemonade, or orange juice and taken immediately.

adults: 20 mg (10 ml, 0.3 oz.) of oral suspension, one
20-mg tablet, or one 25-mg extended-release tablet,
once a day in the morning, increased by 10 mg per
week to a maximum of 50 mg—25 ml (0.75 oz.) of
oral suspension—or a 62.5-mg extended-release
tablet

Missed doses of SSRIs are handled differently
depending on the SSRI and the number of doses
per day. An effective SSRI may be prescribed for
six months or more. Some experts recommend continuing on the SSRI indefinitely to prevent the recurrence
of depression.

GALE ENCYCLOPEDIA OF MEDICINE

287

Antidepressant drugs, SSRI

drinking problems—did not benefit from Zoloft and,
in some cases, increased their alcohol intake.

Antidepressant drugs, SSRI

Precautions



new or worsening depression

Medical conditions



severe worrying

Medical conditions that may affect the use or
dosage of at least some SSRIs include:



irritability



agitation



drug allergies or allergies to other substances in
medications



extreme restlessness



frenzied excitement



mania



panic attacks



manic-depressive (bipolar) disorder



insomnia



brain disease or mental retardation



impulsive behavior



seizures or epilepsy



aggressive behavior



Parkinson s disease





liver or severe kidney disease

thinking about, planning, or attempting to harm
one’s self



abnormal bleeding problems



diabetes mellitus



heart disease

SSRIs remain in the body for some time after the
medication is stopped:



a recent heart attack



Celexa for at least three days



glaucoma



Luvox for at least 32 hours



Paxil for at least 42 hours



Prozac for up to five weeks



Zoloft for at least three to five days

SSRI use during pregnancy may not be safe, particularly during the third trimester. Exposure of fetuses
to Celexa and other SSRIs during the late third trimester have led to very serious complications, including
serotonin syndrome—a condition in which high serotonin levels cause severe problems. Symptoms in a newborn may be the result of a direct toxic effect of the
SSRI or withdrawal from the drug. SSRIs pass into
breast milk and may negatively affect a baby.
Suicidal tendencies
A possible link between SSRIs and suicide
attempts in depressed adults remains controversial.
Three studies in early 2005 drew conflicting conclusions concerning an association between suicidal
behavior and the use of SSRIs. However a February
2005 study found a close correlation between the dramatic decrease in suicides in the United States and
Europe and the introduction of SSRIs.
In October 2004, the FDA concluded that antidepressants, including SSRIs, increased the risk of
suicidal thoughts and behaviors in children and adolescents who suffered from depression and other psychiatric disorders. They recommended extreme
caution in prescribing SSRIs for children. In the last
three months of 2004, SSRI prescriptions for children
and adolescents fell by 10%.
Symptoms that may lead to suicidal tendencies
can develop very suddenly in children and adolescents
taking SSRIs; they may include:
288

Withdrawal

SSRIs can cause what the manufacturers refer to
as ‘‘discontinuation syndrome’’ when the medication
is stopped. Since this occurs most often when the drug
is stopped abruptly, usually the dose is gradually
reduced before stopping the drug completely. The
occurrence of discontinuation syndrome depends on
the SSRI, the dosage, and the length of time that the
drug was used. Paxil appears to induce more serious
withdrawal symptoms than other SSRIs. Symptoms of
Paxil withdrawal appear within 1 to 10 days of stopping the drug. Because of its long half-life in the body,
Prozac rarely causes withdrawal symptoms, although
symptoms have been known to appear within 5 to 42
days of stopping Prozac.
Withdrawal symptoms may include:


generally feeling sick



dry mouth



runny nose



dizziness or lightheadedness



nausea and vomiting



diarrhea



headache



sweating



muscle pain
GALE ENCYCLOPEDIA OF MEDICINE

weakness or fatigue



insomnia



nervousness or anxiety



nervousness or anxiety



restlessness or agitation



tremors



trembling or shaking



sexual problems



insomnia



fast heart rate



breathing difficulties

Most common side effects disappear as the body
adjusts to the drug. Nausea may be relieved by taking
the medication with meals or temporarily dividing the
dose in half.



chest pain



confusion

Although withdrawal symptoms usually wear off,
in some patients some symptoms appear to continue
indefinitely.

Certain side effects occur more frequently depending on the SSRI:


Side effects of Celexa usually are mild and disappear
as the body adjusts.



Luvox and Zoloft are more likely to cause gastrointestinal upset, including stomach irritation, nausea,
and diarrhea.



Paxil is more likely to cause dry mouth, constipation,
and drowsiness. Paxil is significantly more sedating
than other SSRIs, which may benefit patients with
insomnia.



The most common side effect of Prozac is nausea
during the first two weeks on the drug; nervousness
and anxiety also are common with Prozac.

Other precautions
Other precautions concerning SSRIs include:


a 50% chance that an episode of depression will recur
at some point after stopping the drug



a 90% risk of recurrence following two episodes of
depression



reports of patients developing tolerance to an SSRI,
requiring increased dosages for effectiveness



Paxil, Prozac, and Zoloft often reduce appetite.



the long-term effects of SSRIs are unknown





SSRIs are expensive: at least $2–$3 per pill; over $150
for 4 oz. (133 ml) of liquid Prozac

Up to 30% of those on Zoloft suffer headaches and
20% suffer from insomnia.



some insurance plans to not cover mental health
medications.

Studies with Luvox have found that children may
experience different side effects than adults, the most
common being:


dry mouth

Side effects



a stuffy or bloody nose

Common side effects



sweating

The most common side effects of SSRIs include:



drowsiness



dry mouth



restlessness



dizziness



muscle twitching or tics



sour or acid stomach or gas



tremors



heartburn



thinning hair



decreased appetite



abnormal thinking



stomach upset



nausea



diarrhea



sweating



headache



weakness or fatigue



drowsiness

GALE ENCYCLOPEDIA OF MEDICINE

Sexual side effects
Any SSRI can affect sexual interest or performance. Side effects include increased or, more often,
decreased sexual interest, difficulty reaching orgasm
or ejaculation, and impotence.
Although manufacturers initially reported that
sexual problems were very rare side effects of
SSRIs, most patients in clinical trials were never
289

Antidepressant drugs, SSRI



Antidepressant drugs, SSRI

asked specifically about sex and were reluctant to
raise the issue. After a few years it became apparent
that sexual problems were commonplace among
SSRI users, affecting as many as 70%. Among
men taking Paxil, 23% report problems with ejaculation. Between 40% and 70% of those taking
Prozac report negative sexual side effects, especially
loss of interest.
Less common or rare side effects
Less common—but potentially serious—side
effects of at least some SSRIs may include:



lack of emotion, apathy



memory loss

Rare side effects that may occur with some SSRIs
include:


symptoms of low blood sugar or sodium



bleeding gums or nosebleeds



unusual bruising



irregular or slow heartbeat (less than 50 beats per
minute)



fainting



flu-like symptoms



painful urination or other difficulties with urination



sneezing



purple or red spots on the skin



nasal congestion or a runny nose



skin conditions



sore throat



red or irritated eyes



skin rash



inability to move the eyes



itching or tingling, burning, or prickling of the skin



swelling of the face, ankles, or hands



fever



increased or decreased body movements



chills



clumsiness



body aches or pain





muscle or joint pain

tics or other sudden or unusual body or facial movements or postures



abdominal cramps or pain

changes in the breasts, including leakage of milk





vomiting

seizures





decreased or increased appetite

irritability





weight loss

increased depression





weight gain, especially after a year on an SSRI

mood or mental changes





mouth watering

abnormal behaviors





increased frequency or amount of urination

difficulty concentrating





constipation

lethargy or stupor





menstrual changes or pain

hallucinations





chest congestion or pain

suicidal thoughts or tendencies




difficulty breathing



taste changes, including a metallic taste in the mouth



blurred vision or other visual changes



loss of voice



teeth grinding



trembling or shaking



hair loss

Although overdose rarely occurs with SSRIs,
symptoms include two or more severe side effects
occurring together. More common symptoms of
SSRI overdose include:



sensitivity to sunlight



flushing of the face



anxiety or agitation



enlarged pupils



abnormal dreams



fast heart rate



confusion



upset stomach

290

Various other SSRI side effects have been
observed in clinical practice although their incidence
is not known.
Symptoms of overdose

GALE ENCYCLOPEDIA OF MEDICINE

nausea and vomiting



various medications for anxiety, mental illness, or
seizures



sweating



dizziness



sedatives and tranquilizers



irritability



sleeping pills



drowsiness



St. John’s wort



insomnia



trembling or shaking

Drugs that may cause severe heart problems if
taken in conjunction with some SSRIs include:

Rare symptoms of SSRI overdose include:



astemizole (Hismanal)



cisapride (Propulsid)



terfenadine (Seldane)



thioridazine (Mellaril), which should not be taken
for at least five weeks after stopping Prozac



deep or fast breathing with dizziness



fainting



muscle pain



weakness



difficulty urinating



bluish skin or lips

Drugs that may affect the blood levels of an SSRI
or the length of time that an SSRI remains in the body
include:



fast, slow, or irregular heartbeat



antifungal drugs



low blood pressure



cimetidine (Tagamet)



confusion



erythromycin



memory loss



tricyclic antidepressants



seizures





coma

Dilantin and phenobarbitol, which may decrease the
blood levels of Paxil

Interactions
SSRIs interact with many other drugs, often in
similar ways. Alcohol may increase SSRI-induced
drowsiness and should not be used when taking some
SSRIs. Luvox appears to cause the most serious drug
interactions, whereas Celexa has relatively few interactions. A combination of Luvox and Clozaril can cause
low blood pressure and seizures.
The interaction of SSRIs with MAOIs can be
fatal. In addition to antidepressant MAOIs, the
antibiotic linezolid (Zyvox) is an MAOI. There
must be at least a two-week interval between stopping one drug and starting the other. There should
be at least a three-week interval between an MAOI
and either Paxil or Zoloft, if either type of antidepressant was taken for more than three months.
Because of its long half-life in the body, it is necessary to wait five to six weeks after stopping Prozac
before starting on an MAOI.
Some of the drugs that can interact negatively
with SSRIs include:

Some SSRIs may cause higher blood levels of
other medications including:


alprazolam (Xanax and others)



anticoagulants or blood-thinners such as warfarin
(Coumadin)—SSRIs can increase warfarin blood
levels dramatically



aspirin and other nonsteroidal anti-inflammatory
drugs (NSAIDs) including ibuprofen and
naproxen



caffeine



carbamazepine (Tegretol)



diazepam (Valium)



digitalis glycosides (heart medicines)



lithium



methadone



phenytoin (Dilantin and others)



propanolol (Ineral and others)



theophylline or theophylline-containing drugs



other antidepressants



triazolam (Halcion and others)



antihistamines



tricyclic antidepressants

GALE ENCYCLOPEDIA OF MEDICINE

291

Antidepressant drugs, SSRI



Antidepressant drugs, SSRI

Combined treatments

Serotonin syndrome
Rarely, some drugs may interact with an SSRI to
cause serotonin syndrome including:


buspirone (BuSpar)



bromocriptine (Parlodel)



dextromethorphan (cough medicine such as Robitussin
DM)



levodopa (Sinemet)



lithium (Eskalith)



meperidine (Demerol)



moclobemide (Manerex)



nefazodone (Serzone)



pentazocine (Talwin)



other SSRIs



street drugs



sumatriptan (Imitrex)



tramadol (Ultram)



trazodone (Desyrel)



tryptophan



venlafaxine (Effexor)

Increasingly physicians are combining an SSRI
with other medications, either to increase effectiveness
or to counteract side effects. Prozac sometimes is prescribed along with:


an anti-anxiety drug such as Valium (diazepam)



Desyrel (trazodone), a different type of antidepressant, for patients with insomnia



lithium

Resources
BOOKS

Glenmullen, Joseph. Prozac Backlash: Overcoming the
Dangers of Prozac, Zoloft, Paxil, and Other
Antidepressants with Safe, Effective Alternatives. New
York: Simon & Schuster, 2000.
Preskorn, Sheldon H., and Renato D. Alarcón, editors.
Antidepressants: Past, Present, and Future. New York:
Springer, 2004.
Trigoboff, Eileen. Psychiatric Drug Guide. Upper Saddle
River, NJ: Pearson/Prentice Hall, 2005.
PERIODICALS



diarrhea



fever



shivering



sweating



restlessness

Jonsson, Patrik. ‘‘Zoloft Defense Tests Whether Pills Are
Guilty; A Murder Trial Highlights Evolving Legal
Debate Over Whether Antidepressants Limit Personal
Accountability.’’ Christian Science Monitor February
11, 2005: 3.
Sanz, Emilio J., et al. ‘‘Selective Serotonin Reuptake
Inhibitors in Pregnant Women and Neonatal
Withdrawal Syndrome: A Database Analysis.’’ Lancet
365, no. 9458 (February 5, 2005): 482–7.
Treatment for Adolescents With Depression Study (TADS)
Team. ‘‘Fluoxetine, Cognitive-Behavioral Therapy,
and Their Combination for Adolescents with
Depression.’’ Journal of the American Medical
Association 292, no. 7 (August 18, 2004): 807–20.
Whittington, Craig, J., et al. ‘‘Selective Serotonin Reuptake
Inhibitors in Childhood Depression: Systematic Review
of Published Versus Unpublished Data.’’ Lancet 363,
no. 9418 (April 24, 2004): 1341–5.



agitation

ORGANIZATIONS



uncontrollable excitement



poor coordination



twitching



trembling or shaking



rigidity

National Institute of Mental Health. Office of
Communications, 6001 Executive Boulevard, Room
8184, MSC 9663, Bethesda, MD 20892-9663. 866615-6464. 301-443-4513. <http://
www.nimh.nih.gov>.
U.S. Food and Drug Administration. 5600 Fishers Lane,
Rockville, MD 20857-0001. 1-888-INFO-FDA
(1-888-463-6332). <http://www.fda.gov>.



confusion

OTHER



mental changes



fluctuating vital signs

CelexaTM. Forest Pharmaceuticals, Inc. January 2004 [cited
March 6, 2005]. <http://www.fda.gov/medwatch/
SAFETY/2004/apr_PI/Celexa_annotated_PI.pdf>.

Serotonin syndrome may occur shortly after the
dose of a drug is increased.
Serotonin syndrome may be suspected when at
least three of the following symptoms occur
together:

292

GALE ENCYCLOPEDIA OF MEDICINE

Margaret Alic, Ph.D.

I Antidepressants, tricyclic
Definition
Tricyclic antidepressants are medicines that
relieve mental depression.

Purpose
Since their discovery in the 1950s, tricyclic antidepressants have been used to treat mental depression.
Like other antidepressant drugs, they reduce symptoms
such as extreme sadness, hopelessness, and lack of
energy. Some tricyclic antidepressants are also used
to treat bulimia, cocaine withdrawal, panic disorder,
obsessive-compulsive disorders, certain types of
chronic pain, and bed-wetting in children.

Description
Named for their three-ring chemical structure,
tricyclic antidepressants work by correcting chemical
imbalances in the brain. But because they also affect
other chemicals throughout the body, these drugs may
produce many unwanted side effects.
Tricyclic antidepressants are available only with a
physician’s prescription and are sold in tablet, capsule,
GALE ENCYCLOPEDIA OF MEDICINE

liquid, and injectable forms. Some commonly used
tricyclic antidepressants are amitriptyline (Elavil),
desipramine (Norpramin), imipramine (Tofranil),
nortriptyline (Pamelor), and protriptyline (Vivactil).
Different drugs in this family have different effects,
and physicians can choose the drug that best fits the
patient’s symptoms. For example, a physician might
prescribe Elavil for a person with depression who has
trouble sleeping, because this drug is more likely to
make people feel calm and sleepy. Other tricyclic antidepressants might be more appropriate for depressed
people with low energy.

Recommended dosage
The recommended dosage depends on many factors, including the patient’s age, weight, general health
and symptoms. The type of tricyclic antidepressant
and its strength also must be considered. Check with
the physician who prescribed the drug or the pharmacist who filled the prescription for the correct dosage.
Always take tricyclic antidepressants exactly as
directed. Never take larger or more frequent doses,
and do not take the drug for longer than directed.
Do not stop taking the medicine just because it does
not seem to be working. Several weeks may be needed
for its effects to be felt. Visit the physician as often as
recommended so that the physician can check to see if
the drug is working and to note for side effects.
Do not stop taking this medicine suddenly after
taking it for several weeks or more. Gradually tapering the dose may be necessary to reduce the chance of
withdrawal symptoms.
Taking this medicine with food may prevent upset
stomach.

Precautions
The effects of this medicine may continue for three
to seven days after patients stop taking it. All precautions should be observed during this period, as well as
throughout treatment with tricyclic antidepressants.
Some people feel drowsy, dizzy, or lightheaded,
when taking these drugs. The drugs may also cause
blurred vision. Anyone who takes these drugs should
not drive, use machines or do anything else that might
be dangerous until they have found out how the drugs
affect them.
Because tricyclic antidepressants work on the central nervous system, they may add to the effects of
alcohol and other drugs that cause drowsiness, such
as antihistamines, cold medicine, allergy medicine,
293

Antidepressants, tricyclic

Edelson, Ed. ‘‘Suicide Risk from Antidepressants Remains
Unclear.’’ HealthDayNews. National Health
Information Center, U.S. Department of Health and
Human Services. February 17, 2005 [cited March 6,
2005]. <http://www.healthfinder.gov/news/
newsstory.asp?docid=524064>.
LexaproTM. Forest Pharmaceuticals, Inc. December 2003
[cited March 6, 2005]. <http://www.fda.gov/cder/foi/
label/2003/21323se1-003,se8-007,21365se8-001,se1004_lexapro_lbl.pdf>.
Medications. National Institute of Mental Health. April 9,
2004 [cited March 13, 2005]. <http://www.nimh.nih.gov/publicat/medicate.cfm>.
Mundell, E. J. ‘‘Study: Benefits of Antidepressants
Outweigh Risks.’’ HealthDayNews. National Health
Information Center, U.S. Department of Health and
Human Services. February 2, 2005 [cited March 25,
2005]. <http://www.healthfinder.gov/news/
newsstory.asp?docid=523762>.
Turkington, Carol, and Eliot F. Kaplan. Selective Serotonin
Reuptake Inhibitors (SSRIs). WebMD Medical
Reference. 2001 [cited March 23, 2005]. <http://
my.webmd.com/content/Article/87/99352.htm>.

Antidepressants, tricyclic

KEY TERMS
Asthma—A disease in which the air passages of the
lungs become inflamed and narrowed.
Bulimia—An eating disorder in which a person
binges on food and then induces vomiting, uses
laxatives, or goes without food for some time.
Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Delusion—An abnormal mental state characterized
by the acceptance of something as true that is actually
false or unreal, such as the belief that one is Jesus Christ.
Depression—A mental condition in which a person
feels extremely sad and loses interest in life. A
person with depression may also have sleep problems and loss of appetite and may have trouble
concentrating and carrying out everyday activities.
Glaucoma—A condition in which pressure in the
eye is abnormally high. If not treated, glaucoma
may lead to blindness.
Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Obsessive-compulsive disorder—An anxiety disorder in which a person cannot prevent himself from
dwelling on unwanted thoughts, acting on urges, or
performing repetitious rituals, such as washing his
hands or checking to make sure he turned off the lights.
Panic disorder—An disorder in which a person has
sudden and intense attacks of anxiety in certain
situations. Symptoms such as shortness of breath,
sweating, dizziness, chest pain, and extreme fear
often accompany the attacks.
Prostate—A donut-shaped gland in males below the
bladder that contributes to the production of semen.
Schizophrenia—A severe mental disorder in which
a person loses touch with reality and may have
illogical thoughts, delusions, hallucinations, behavioral problems and other disturbances.
Seizure—A sudden attack, spasm, or convulsion.
Serotonin—A natural chemical found in the brain
and other parts of the body, that carries signals
between nerve cells.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug to which he or she has
become dependent.

294

sleep aids, medicine for seizures, tranquilizers, some
pain relievers, and muscle relaxants. Anyone taking
tricyclic antidepressants should check with his or her
physician before drinking alcohol or taking any drugs
that cause drowsiness.
These medicines make some people feel lightheaded, dizzy, or faint when they get up after sitting
or lying down. To lessen the problem, get up gradually
and hold onto something for support if possible.
Tricyclic antidepressants may interact with medicines used during surgery, dental procedures, or emergency treatment. These interactions could increase the
chance of side effects. Anyone who is taking tricyclic
antidepressants should be sure to tell the health care
professional in charge before having any surgical or
dental procedures or receiving emergency treatment.
These drugs may also change the results of medical tests. Before having medical tests, anyone taking
this medicine should alert the health care professional
in charge.
This medicine may increase sensitivity to sunlight.
Even brief exposure to sun can cause a severe sunburn or
a rash. While being treated with this tricyclic antidepressants, avoid being in direct sunlight, especially
between 10 A.M. and 3 P.M.; wear a hat and tightly
woven clothing that covers the arms and legs; use a
sunscreen with a skin protection factor (SPF) of at
least 15; protect the lips with a sun block lipstick; and
do not use tanning beds, tanning booths, or sunlamps.
Tricyclic antidepressants may cause dry mouth. To
temporarily relieve the discomfort, chew sugarless
gum, suck on sugarless candy or ice chips, or use saliva
substitutes, which come in liquid and tablet forms and
are available without a prescription.
Children and older people are especially sensitive to
the effects of tricyclic antidepressants. This increased
sensitivity may increase the chance of side effects.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take tricyclic antidepressants. Before taking these
drugs, be sure to let the physician know about any of
these conditions:
ALLERGIES. Anyone who has had unusual reactions to tricyclic antidepressants or to carbamazepine
(Tegretol), maprotiline (Ludiomil), or trazodone
(Desyrel) in the past should let his or her physician
know before taking tricyclic antidepressants. The physician should also be told about any allergies to foods,
dyes, preservatives, or other substances.

GALE ENCYCLOPEDIA OF MEDICINE

BREASTFEEDING. Tricyclic

antidepressants pass
into breast milk and may cause drowsiness in nursing
babies whose mothers take the drugs. Women who are
breastfeeding should check with their physicians
before using tricyclic antidepressants.

More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with the physician who prescribed the medicine
as soon as possible:


blurred vision



eye pain



confusion



hallucinations



fainting



loss of balance



swallowing problems



difficulty speaking



mask-like face



shakiness or trembling



nervousness or restlessness



movement problems, such as shuffling walk, stiff
arms and legs, or slow movement

DIABETES. Tricyclic antidepressants may affect

blood sugar levels. Diabetic patients who notice
changes in blood or urine test results while taking
this medicine should check with their physicians.
OTHER MEDICAL CONDITIONS. Before using tri-

cyclic antidepressants, people with any of these medical problems should make sure their physicians are
aware of their conditions:


current or past alcohol or drug abuse



bipolar disorder (manic-depressive illness)



schizophrenia



decreased sexual ability



seizures (convulsions)



fast or irregular heartbeat



heart disease



constipation



high blood pressure



problems urinating



kidney disease



liver disease



overactive thyroid

Some side effects may continue after treatment
with tricyclic antidepressants has ended. Check with
a physician if these symptoms occur:



stomach or intestinal problems



enlarged prostate



problems urinating



glaucoma



asthma
USE OF CERTAIN MEDICINES. Taking tricyclic anti-

depressants with certain other drugs may affect the way
the drugs work or may increase the chance of side effects.

Side effects
The most common side effects are dizziness, drowsiness, dry mouth, unpleasant taste, headache, nausea,
mild tiredness or weakness, increased appetite or craving for sweets, and weight gain. These problems
usually go away as the body adjusts to the drug and
do not require medical treatment. Less common side
effects, such as diarrhea, vomiting, sleep problems,
sweating, and heartburn also may occur and do not
need medical attention unless they do not go away or
they interfere with normal activities.
GALE ENCYCLOPEDIA OF MEDICINE



headache



nausea, vomiting, or diarrhea



sleep problems, including vivid dreams



unusual excitement, restlessness, or irritability

Interactions
Life-threatening reactions, such as extrememly high
blood pressure, may occur when tricyclic antidepressants are taken with other antidepressants called monoamine oxidase (MAO) inhibitors (such as Nardil
and Parnate). Do not take tricyclic antidepressants within
2 weeks of taking a MAO inhibitor. However, a patient
can take an MAO inhibitor immediately after tricyclic
antidepressant therapy is stopped by the physician.
Tricyclic antidepressants may interact with many
other medicines. When this happens, the effects of one
or both of the drugs may change or the risk of side
effects may be greater. Anyone who takes tricyclic
antidepressants should let the physician know all
other medicines he or she is taking. Among the drugs
that may interact with tricyclic antidepressants are:
295

Antidepressants, tricyclic

PREGNANCY. Problems have been reported in
babies whose mothers took tricyclic antidepressants
just before delivery. Women who are pregnant or who
may become pregnant should check with their physicians about the safety of using tricyclic antidepressants.

Antidiabetic drugs



Central nervous system (CNS) depressants such as
medicine for allergies, colds, hay fever, and asthma;
sedatives; tranquilizers; prescription pain medicine;
muscle relaxants; medicine for seizures; sleep aids;
barbiturates; and anesthetics.



diet pills



amphetamines



blood thinning drugs



medicine for overactive thyroid



cimetidine (Tagamet)



other antidepressant drugs, including MAO inhibitors (such as Nardil and Parnate) and antidepressants that raise serotonin levels (such as Prozac and
Zoloft)



blood pressure medicines such as clonidine (Catapres)
and guanethidine monosulfate (Ismelin)



disulfiram (Antabuse), used to treat alcohol abuse



major tranquilizers such as thioridazine (Mellaril)
and chlorpromazine (Thorazine)



antianxiety drugs such as chlordiazepoxide (Librium)
and alprazolam (Xanax)



antiseizure medicines such as carbamazaepine
(Tegretol) and phenytoin (Dilantin)

The list above does not include every drug that
may interact with tricyclic antidepressants. Be sure to
check with a physician or pharmacist before combining tricyclic antidepressants with any other prescription or nonprescription (over-the-counter) medicine.

KEY TERMS
Blood sugar—The concentration of glucose in the
blood.
Glucose—A simple sugar that serves as the body’s
main source of energy.
Hormone—A substance that is produced in one part
of the body, then travels through the bloodstream to
another part of the body where it has its effect.
Metabolism—All the physical and chemical changes
that occur in cells to allow growth and maintain
body functions. These include processes that break
down substances to yield energy and processes
that build up other substances necessary for life.
Pregnancy category— A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B:
Animal studies indicate no fetal risk, but no
human studies; or adverse effects in animals, but
not in well-controlled human studies. Category C:
No adequate human or animal studies; or adverse
fetal effects in animal studies, but no available
human data. Category D: Evidence of fetal risk,
but benefits outweigh risks. Category X: Evidence
of fetal risk. Risks outweigh any benefits.
Salicylates—A group of drugs that includes aspirin
and related compounds. Salicylates are used to
relieve pain, reduce inflammation, and lower fever.
Seizure—A sudden attack, spasm, or convulsion.

Nancy Ross-Flanigan

I Antidiabetic drugs
Definition
Antidiabetic drugs are medicines that help control
blood sugar levels in people with diabetes mellitus
(sugar diabetes).

Purpose
Diabetes may be divided into type I and type II,
formerly termed juvenile onset or insulin-dependent,
and maturity onset or non insulin-dependent. Type I is
caused by a deficiency of insulin production, while
type II is characterized by insulin resistance.
296

Treatment of type I diabetes is limited to insulin
replacement, while type II diabetes is treatable by a
number of therapeutic approaches. Many cases of insulin resistance are asymptomatic due to normal increases
in insulin secretion, and others may be controlled by
diet and exercise. Drug therapy may be directed toward
increasing insulin secretion, increasing insulin sensitivity, or increasing insulin penetration of the cells.

Description
Antidiabetic drugs may be subdivided into six
groups: insulin, sufonylureas, alpha-glucosidase inhibitors, biguanides, meglitinides, and thiazolidinediones.
Insulin (Humulin, Novolin) is the hormone responsible for glucose utilization. It is effective in both types
of diabetes, since, even in insulin resistance, some sensitivity remains and the condition can be treated with
GALE ENCYCLOPEDIA OF MEDICINE

Sulfonylureas (chlorpropamide [Diabinese], tolazamide [Tolinase], glipizide [Glucotrol] and others) act
by increasing insulin release from the beta cells of the
pancrease. Glimepiride (Amaryl), a member of this
class, appears to have a useful secondary action in
increasing insulin sensitivity in peripheral cells.
Alpha-glucosidase inhibitors (acarbose [Precose],
miglitol [Glyset]) do not enhance insulin secretion.
Rather, they inhibit the conversion of disaccharides and
complex carbohydrates to glucose. This mechanism does
not prevent conversion, but only delays it, reducing the
peak blood glucose levels. Alpha-glucosidase inhibitors
are useful for either monotherapy or in combination
therapy with sulfonylureas or other hypoglycemic agents.
Metformin (Glucophage) is the only available member of the biguanide class. Metformin decreases hepatic
(liver) glucose production, decreases intestinal absorption of glucose and increases peripheral glucose uptake
and use. Metformin may be used as monotherapy
(alone), or in combination therapy with a sulfonylurea.
There are two members of the meglitinide class:
repaglinide (Prandin) and nateglitinide (Starlix). The
mechanism of action of the meglitinides is to stimulate
insulin production. This activity is both dose dependent
and dependent on the presence of glucose, so that the
drugs have reduced effectiveness in the presence of low
blood glucose levels. The meglitinides may be used alone,
or in combination with metformin. The manufacturer
warns that nateglitinide should not be used in combination with other drugs that enhance insulin secretion.
Rosiglitazone (Avandia) and pioglitazone (Actos)
are members of the thiazolidinedione class. They act
by both reducing glucose production in the liver, and
increasing insulin dependent glucose uptake in muscle
cells. They do not increase insulin production. These
drugs may be used in combination with metformin or
a sulfonylurea.

Recommended dosage
Dosage must be highly individualized for all antidiabetic agents and is based on blood glucose levels
GALE ENCYCLOPEDIA OF MEDICINE

which must be taken regularly. Patients should review
specific literature that comes with antidiabetic medications for complete dosage information.

Precautions
Insulin. The greatest short term risk of insulin is
hypoglycemia, which may be the result of either a
direct overdose or an imbalance between insulin injection and level of exercise and diet. This also may occur
in the presence of other conditions which reduce the
glucose load, such as illness with vomiting and diarrhea. Treatment is with glucose in the form of glucose
tablets or liquid, although severe cases may require
intravenous therapy. Allergic reactions and skin reactions also may occur. Insulin is classified as category B
in pregnancy, and is considered the drug of choice for
glucose control during pregnancy. Insulin glargine
(Lantus), an insulin analog which is suitable for
once-daily dosing, is classified as category C, because
there have been reported changes in the hearts of newborns in animal studies of this drug. The reports are
essentially anecdotal, and no cause and effect relationship has been determined. Insulin is not recommended
during breast feeding because either low or high
doses of insulin may inhibit milk production. Insulin
administered orally is destroyed in the GI tract, and
represents no risk to the newborn.
Sulonylureas. All sulfonylurea drugs may cause
hypoglycemia. Most patients become resistant to these
drugs over time, and may require either dose adjustments or a switch to insulin. The list of adverse reactions
is extensive, and includes central nervous system problems and skin reactions, among others. Hematologic
reactions, although rare, may be severe and include
aplastic anemia and hemolytic anemia. The administration of oral hypoglycemic drugs has been associated
with increased cardiovascular mortality as compared
with treatment with diet alone or diet plus insulin. The
sulfonylureas are classified as category C during pregnancy, based on animal studies, although glyburide has
not shown any harm to the fetus and is classified as
category B. Because there may be significant alterations
in blood glucose levels during pregnancy, it is recommended that patients be switched to insulin. These drugs
have not been fully studied during breast feeding, but it
is recommended that because their presence in breast
milk might cause hypoglycemia in the newborn, breast
feeding be avoided while taking sulfonylureas.
Alpha-glucosidase inhibitors are generally well
tolerated, and do not cause hypoglycemia. The most
common adverse effects are gastrointestinal problems,
including flatulence, diarrhea, and abdominal pain.
297

Antidiabetic drugs

larger doses of insulin. Most insulins are now produced
by recombinant DNA techniques, and are chemically
identical to natural human insulin. Isophane insulin
suspension, insulin zinc suspension, and other formulations are intended to extend the duration of insulin
action, and permit glucose control over longer periods
of time. In 2003, research suggested that inhaled forms
of insulin offered advantages to injected types, but
further study was needed on its long-term effects on
the lungs and cost-effectiveness.

Antidiarrheal drugs

These drugs are classified as category B in pregnancy.
Although there is no evidence that the drugs are harmful to the fetus, it is important that rigid blood glucose
control be maintained during pregnancy, and pregnant women should be switched to insulin. Alphaglucosidase inhibitors may be excreted in small
amounts in breast milk, and it is recommended that
the drugs not be administered to nursing mothers.
Metformin causes gastrointestinal (stomach and
digestive) reactions in about a third of patients. A rare,
but very serious, reaction to metformin is lactic acidosis, which is fatal in about 50% of cases. Lactic acidosis occurs in patients with multiple medical problems,
including renal (kidney-related) insufficiency. The risk
may be reduced with careful renal monitoring, and
careful dose adjustments to metformin. Metformin is
category B during pregnancy. There have been no
carefully controlled studies of the drug during pregnancy, but there is no evidence of fetal harm from
animal studies. It is important that rigid blood glucose
control be maintained during pregnancy, and pregnant women should be switched to insulin. Animal
studies show that metformin is excreted in milk. It is
recommended that metformin not be administered to
nursing mothers.
Meglitinides. These drugs are generally well tolerated, with an adverse event profile similar to placebo. The drugs are classified as category C during
pregnancy, based on fetal abnormalities in rabbits
given about 40 times the normal human dose. It is
important that rigid blood glucose control be maintained during pregnancy, and pregnant women
should be switched to insulin. It is not known
whether the meglitinides are excreted in human
milk, but it is recommended that these drugs not be
given to nursing mothers.
Thiazolidinediones. These drugs were generally
well tolerated in early trials, but they are structurally
related to an earlier drug, troglitazone, which was
associated with liver function problems. However, in
2003, researchers reported that these drugs, which are
used by more than 6 million Americans, may lead to
serious side effects. Research showed that after one to
16 months of therapy with pioglitazone or rosiglitazone, some patients developed serious edema and signs
of congestive heart failure. Additional studies were
underway in late 2003 to determine how these drugs
caused fluid build-up and if the symptoms occurred
more frequently in certain age groups. The mean age
of patients in the 2003 study was 69 years.
It is strongly recommended that all patients treated
with pioglitazone or rosiglitazone have regular liver
298

function monitoring. The drugs are classified as pregnancy category C, based on evidence of inhibition of
fetal growth in rats given more than four times the
normal human dose. It is important that rigid blood
glucose control be maintained during pregnancy, and
pregnant women should be switched to insulin. It is not
known whether the thiazolidinediones are excreted in
human milk, however they have been identified in the
milk of lactating rats. It is recommended that these
drugs not be administered to nursing mothers.

Interactions
The sulfonylureas have a particularly long list of
drug interactions, several of which may be severe.
Patients should review specific literature for these drugs.
The actions of oral hypoglycemic agents may be
strengthened by highly protein bound drugs, including
NSAIDs, salicylates, sulfonamides, chloramphenicol,
coumarins, probenecid, MAOIs, and beta blockers.
The literature that accompanies each medication
should list possible drug-drug or food-drug interactions.
Resources
PERIODICALS

‘‘Inhaled Insulin Means Better Quality of Life.’’ Health &
Medicine Week (September 16, 2003): 189.
‘‘Two Common Diabetes Drugs May Cause Heart Failure
and Fluid Buildup.’’ Cardiovascular Week (September
29, 2003): 26.
ORGANIZATIONS

American Diabetes Association. ADA National Service
Center, 1660 Duke Street, Alexandria, VA 22314.
(800)232-3472. <http://www.diabetes.org>.
National Diabetes Information Clearinghouse. 1
Information Way, Bethesda, MD 20892-3560.
(301)654-3327. ndic@info.niddk.nih.gov.
OTHER

National Institute of Diabetes and Digestive and Kidney
Diseases. <http://www.niddk.nih.gov>.

Samuel D. Uretsky, PharmD
Teresa G. Odle

I Antidiarrheal drugs
Definition
Antidiarrheal drugs are medicines that relieve
diarrhea.
GALE ENCYCLOPEDIA OF MEDICINE

Colitis—Inflammation of the colon (large bowel).
Dehydration—Excessive loss of water from the
body.
Enzyme—A type of protein, produced in the body,
that brings about or speeds up chemical reactions.
Nutrient—A food substance that provides energy or
is necessary for growth and repair. Examples of nutrients are vitamins, minerals, carbohydrates, fats, and
proteins.

Purpose
Antidiarrheal drugs help control diarrhea and some
of the symptoms that go along with it. An average,
healthy person has anywhere from three bowel movements a day to three a week, depending on that person’s
diet. Normally the stool (the material that is passed in a
bowel movement) has a texture something like clay.
With diarrhea, bowel movements may be more frequent,
and the texture of the stool is thin and sometimes watery.
Diarrhea is not a disease, but a symptom of some
other problem. The symptom may be caused by eating
or drinking food or water that is contaminated with
bacteria, viruses, or parasites, or by eating something
that is difficult to digest. People who have trouble
digesting lactose (milk sugar), for example, may get
diarrhea if they eat dairy products. Some cases of
diarrhea are caused by stress, while others are brought
on by taking certain medicines.

Description
Antidiarrheal drugs work in several ways. The
drug loperamide, found in Imodium A-D, for example,
slows the passage of stools through the intestines. This
allows more time for water and salts in the stools to be
absorbed back into the body. Adsorbents, such as attapulgite (found in Kaopectate) pull diarrhea-causing
substances from the digestive tract. However, they
may also pull out substances that the body needs,
such as enzymes and nutrients. Bismuth subsalicylate,
the ingredient in Pepto-Bismol, decreases the secretion
of fluid into the intestine and inhibits the activity of
bacteria. It not only controls diarrhea, but relieves the
cramps that often accompany diarrhea.
These medicines come in liquid, tablet, caplet, and
chewable tablet forms and can be bought without a
physician’s prescription.
GALE ENCYCLOPEDIA OF MEDICINE

The dose depends on the type of antidiarrheal
drug. Read and follow the directions on the product
label. For questions about dosage, check with a physician or pharmacist. Never take larger or more frequent doses, and do not take the drug for longer than
directed.

Precautions
Diarrhea usually improves within 24-48 hours. If
the problem lasts longer or if it keeps coming back,
diarrhea could be a sign of a more serious problem.
Anyone who has any of the symptoms listed below
should get medical attention as soon as possible:


diarrhea that lasts more than two days or gets worse



fever



blood in the stool



vomiting



cramps or tenderness in the abdomen



signs of dehydration, such as decreased urination,
dizziness or lightheadedness, dry mouth, increased
thirst, or wrinkled skin

Do not use antidiarrheal drugs for more than two
days unless told to do so by a physician.
Severe, long-lasting diarrhea can lead to dehydration. In such cases, lost fluids and salts, such as
calcium, sodium, and potassium, must be replaced.
People older than 60 should not use attapulgite
(Kaopectate, Donnagel, Parepectolin), but may use
other kinds of antidiarrheal drugs. However, people
in this age group may be more likely to have side
effects, such as severe constipation, from bismuth subsalicylate. Ask the pharmacist for more information.
Bismuth subsalicylate may cause the tongue or the
stool to temporarily darken. This is harmless.
However, do not confuse this harmless darkening of
the stool with the black, tarry stools that are a sign of
bleeding in the intestinal tract.
Children with flu or chicken pox should not be
given bismuth subsalicylate. It can lead to Reye’s syndrome, a life-threatening condition that affects the
liver and central nervous system. To be safe, never
give bismuth subsalicylate to a child under 16 years
without consulting a physician. Children may have
unpredictable reactions to other antidiarrheal drugs.
Loperamide should not be given to children under six
years and attapulgite should not be given to children
under three years unless directed by a physician.
299

Antidiarrheal drugs

Recommended dosage

KEY TERMS

Antidiuretic hormone (ADH) test

Anyone who has a history of liver disease or who
has been taking antibiotics should check with his or her
physician before taking the antidiarrheal drug loperamide. A physician should also be consulted before
anyone with acute ulcerative colitis or anyone who has
been advised to avoid constipation uses the drug.
Loperamide should not be used by people whose
diarrhea is caused by certain infections, such as salmonella or shigella. To be safe, check with a physician
before using this drug.
Anyone who has a medical condition that causes
weakness should check with a physician about the best
way to treat diarrhea.
Special conditions
Before taking antidiarrheal drugs, be sure to let
the physician know about any of these conditions:
ALLERGIES. Anyone who has had unusual reactions
to aspirin or other drugs containing salicylates should
check with a physician before taking bismuth subsalicylate. Anyone who has developed a rash or other
unusual reactions after taking loperamide should not
take that drug again without checking with a physician.
The physician should also be told about any allergies to
foods, dyes, preservatives, or other substances.
PREGNANCY AND BREASTFEEDING. Women who
are pregnant or breastfeeding should check with their
physicians before using antidiarrheal drugs. They should
also ask advice on how to replace lost fluids and salts.
OTHER MEDICAL CONDITIONS. Before using antidiarrheal drugs, people with any of these medical problems should make sure their physicians are aware of
their conditions:


dysentery



gout



hemophilia or other bleeding problems



kidney disease



stomach ulcer



severe colitis



liver disease

USE OF CERTAIN MEDICINES. Taking antidiarrheal
drugs with certain other drugs may affect the way the
drugs work or may increase the chance of side effects.

Side effects
The most common side effects of attapulgite
are constipation, bloating, and fullness. Bismuth
subsalicylate may cause ringing in the ears, but
300

that side effect is rare. Possible side effects from
loperamide include skin rash, constipation, drowsiness, dizziness, tiredness, dry mouth, nausea, vomiting, and swelling, pain, and discomfort in the
abdomen. Some of these symptoms are the same
as those that occur with diarrhea, so it may be
difficult to tell if the medicine is causing the problems. Children may be more sensitive than adults
to certain side effects of loperamide, such as drowsiness and dizziness.
Other rare side effects may occur with any antidiarrheal medicine. Anyone who has unusual symptoms after taking an antidiarrhea drug should get in
touch with his or her physician.

Interactions
Attapulgite can decrease the effectiveness of other
medicines taken at the same time. Changing the times
at which the other medicines are taken may be necessary. Check with a physician or pharmacist to work
out the proper dose schedule.
Bismuth subsalicylate should not be taken with
aspirin or any other medicine that contains salicylate.
This drug may also interact with other drugs, such as
blood thinners (warfarin, for example), methotrexate,
the antigout medicine probenecid, and the antidiabetes drug tolbutamide. In addition, bismuth subsalicylate may interact with any drug that interacts with
aspirin. Anyone taking these drugs should check with
a physician or pharmacist before taking bismuth
subsalicylate.
Nancy Ross-Flanigan

hormone (ADH)
I Antidiuretic
test
Definition
Antidiuretic hormone (ADH) test, also called the
Vasopressin test, is a test for the antidiuretic hormone,
which is released from the pituitary gland and acts on
the kidneys to increase their reabsorption of water into
the blood.

Purpose
An ADH test is used to aid in the diagnosis of
diabetes insipidus or the syndrome of inappropriate
ADH called SIADH.
GALE ENCYCLOPEDIA OF MEDICINE

Diabetes insipidus—A metabolic disorder in which
the pituitary gland produces inadequate amounts of
antidiuretic hormone (ADH) or the kidneys are unable
to respond to release of the hormone. Primary symptoms are excessive urination and constant thirst.
Pituitary gland—The pituitary gland is sometimes
referred to as the ‘‘master gland.’’ As the most important of the endocrine glands (glands which release
hormones directly into the bloodstream), it regulates
and controls not only the activities of other endocrine glands but also many body processes.

The test requires collection of a blood sample. The
patient must be fasting (nothing to eat or drink) for
12 hours, be adequately hydrated, and limit physical
activity for 10-12 hours before the test.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or
feeling lightheaded after venipuncture, or hematoma
(blood accumulating under the puncture site).

Normal results
ADH normal ranges are laboratory-specific but
can range from 1-5 pg/ml or 1.5 ng/L (SI units).

Precautions
Certain drugs can either increase or decrease
ADH levels. Drugs that increase ADH levels include
acetaminophen, barbiturates, cholinergic agents, estrogen, nicotine, oral hypoglycemia agents, some diuretics
(e.g., thiazides), cyclophosphamide, narcotics, and tricyclic antidepressants. Drugs that decrease ADH levels
include alcohol, beta-adrenergic agents, morphine
antagonists, and phenytoin (Dilantin).

Description
The purpose of ADH is to control the amount of
water reabsorbed by the kidneys. Water is continually being taken into the body in food and drink, as
well as being produced by chemical reactions in cells.
Water is also continually lost in urine, sweat, feces,
and in the breath as water vapor. ADH release helps
maintain the optimum amount of water in the body
when there is an increase in the concentration of the
blood serum or a decrease in blood volume. Physical
stress, surgery, and high levels of anxiety can also
stimulate ADH.
Various factors can affect ADH production,
thereby disturbing the body’s water balance. For
example, alcohol consumption reduces ADH production by direct action on the brain, resulting in a
temporarily increased production of urine. This may
also occur in diabetes insipidus, when the pituitary
gland produces insufficient ADH, or rarely, when the
kidneys fail to respond to ADH. The reverse effect of
water retention can result from temporarily
increased ADH production after a major operation
or accident. Water retention may also be caused by
the secretion of ADH by some tumors, especially of
the lung.
GALE ENCYCLOPEDIA OF MEDICINE

Abnormal results
Patients who are dehydrated, who have a decreased
amount of blood in the body (hypovolemia), or who are
undergoing severe physical stress (e.g., trauma, pain or
prolonged mechanical ventilation) may exhibit increased
ADH levels. Patients who are overly hydrated or who
have an increased amount of blood in the body (hypervolemia) may have decreased ADH levels.
Other conditions that cause increased levels
include SIADH, central nervous system tumors or
infection, or pneumonia.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Antiemetic drugs see Antinausea drugs
Antiepileptic drugs see Anticonvulsant drugs

I Antifungal drugs, systemic
Definition
Systemic antifungal drugs are medicines taken by
mouth or by injection to treat deep infections caused
by a fungus.
301

Antifungal drugs, systemic

Preparation

KEY TERMS

Antifungal drugs, systemic

Description

KEY TERMS
Elixir—A sweetened liquid that contains alcohol,
water, and medicine.
Fetus—A developing baby inside the womb.
Fungus—A unicellular to filamentous organism
that causes parasitic infections.
Ointment—A thick substance that contains medicine and is meant to be spread on the skin, or if an
ophthalmic ointment, in the eye.
Systemic—A term used to describe a medicine
that has effects throughout the body, as opposed
to topical drugs that work on the skin. Most medicines that are taken by mouth or by injection are
systemic drugs.

Purpose
Systemic antifungal drugs are used to treat
infections in various parts of the body that are
caused by a fungus. A fungus is an organism that
can be either one-celled or filamentous. Unlike a
plant, which makes its own food, or an animal,
which eats plants or other animals, a fungus survives by invading and living off other living things.
Fungi thrive in moist, dark places, including some
parts of the body.
Fungal infections can either be systemic, meaning
that the infection is deep, or topical (dermatophytic),
meaning that the infection is superficial and occurs on
the skin. Additionally, yeast infections can affect the
mucous membranes of the body. Fungal infections on
the skin are usually treated with creams or ointments
(topical antifungal drugs). However, systemic infections, yeast infections or topical infections that do
not clear up after treatment with creams or ointments
may need to be treated with systemic antifungal drugs.
These drugs are used, for example, to treat common
fungal infections such as tinea (ringworm), which
occurs on the skin or candidiasis (a yeast infection,
also known as trush), which can occur in the throat,
in the vagina, or in other parts of the body. They are
also used to treat other deep fungal infections such as
histoplasmosis, blastomycosis, and aspergillosis, which
can affect the lungs and other organs. They are sometimes used to prevent or treat fungal infections in
people whose immune systems are weakened, such as
bone marrow or organ transplant patients and people
with AIDS.
302

Antifungal drugs are categorized depending on
their route or site of action, their mechanism of action
and their chemical nature.
Systemic antifungal drugs, such as capsofungin
(Cancidas), flucytosine, fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), and
miconazole (Monistat I.V.) are available only by prescription. They are available in tablet, capsule, liquid,
and injectable forms.

Recommended dosage
The recommended dosage depends on the type of
antifungal drug and the nature and extent of fungal
infection being treated. Doses may also be different for
different patients. The prescribing physician or the
pharmacist can provide dosage information.
Systemic antifungal drugs must be taken exactly as
directed. Itraconazole and ketoconazole should be
taken with food.
Fungal infections can take a long time to clear up,
so it may be necessary to take the medication for several
months, or even for a year or longer. It is very important to keep taking the medicine for as long as the
physician says to take it, even if symptoms seem to
improve. If the drug is stopped too soon, the symptoms
may return.
Systemic antifungal drugs work best when their
amount is kept constant in the body, meaning that
they have to be taken regularly, at the same time
every day, and without missing any doses.
Patients taking the liquid form of ketoconazole
should use a specially marked medicine spoon or other
medicine measuring device to make sure they take the
correct amount. A regular household teaspoon may
not hold the right amount of medicine. Ask the pharmacists about ways to accurately measure the dose of
these drugs.

Precautions
If symptoms do not improve within a few weeks,
the prescribing physician should be informed.
While taking this medicine, regular medical visits
should be scheduled. The physician needs to keep
checking for side effects throughout the antifungal
therapy.
Some people feel drowsy or dizzy while taking
systemic antifungal drugs. Anyone who takes these
drugs should not drive, use machines or do anything
GALE ENCYCLOPEDIA OF MEDICINE

Liver problems, stomach problems and other problems may occur in people who drink alcohol while
taking systemic antifungal drugs. Alcohol and prescription or nonprescription (over-the-counter) drugs
that contain alcohol should be avoided while taking
antifungal drugs. (Medicines that may contain alcohol
include some cough syrups, tonics, and elixirs.)
Alcohol should be avoided for at least a day after
taking an antifungal drug.
The antifungal drug ketoconazole may make the
eyes unusually sensitive to light. Wearing sunglasses
and avoiding exposure to bright light may help.

ineffective. For people with insufficient stomach acid,
it may help to take the medicine with an acidic drink,
such as a cola. The patient’s health care provider can
suggest the best way to take the medicine.
Before using systemic antifungal drugs, people
with any of these medical problems should also make
sure their physicians are aware of their conditions:


current or past alcohol abuse



liver disease



kidney disease

USE OF CERTAIN MEDICINES. Taking systemic antifungal drugs with certain other drugs may affect the
way the drugs work or may increase the chance of side
effects.

Special conditions
People with certain medical conditions or who
are taking certain other medicines can have problems if they take systemic antifungal drugs.
Before taking these drugs, the prescribing physician
should be informed about any of the following
conditions:
ALLERGIES. Anyone who has had unusual reactions to systemic antifungal drugs in the past should
let his or her physician know about the problem before
taking the drugs again. The physician should also be
told about any allergies to foods, dyes, preservatives,
or other substances.

Side effects
Fluconazole
Although rare, severe allergic reactions to this
medicine have been reported. Call a physician immediately if any of these symptoms develop after taking
fluconazole (Diflucan):


hives, itching, or swelling



breathing or swallowing problems



sudden drop in blood pressure



diarrhea



abdominal pain

PREGNANCY. In laboratory studies of animals,

systemic antifungal drugs have caused birth defects
and other problems in the mother and fetus.
Studies have not been done on pregnant women,
so it is not known whether these drugs cause similar effects in people. Women who are pregnant or
who plan to become pregnant should check with
their physicians before taking systemic antifungal
drugs. Any woman who becomes pregnant while
taking these drugs should let her physician know
immediately.
BREASTFEEDING. Systemic antifungal drugs pass
into breast milk. Women who are breastfeeding
should check with their physicians before using systemic antifungal drugs.
OTHER MEDICAL CONDITIONS. People who have
medical conditions that deplete stomach acid (achlorhydria) or decrease stomach acid (hypochlorhydria)
should be sure to inform their physicians about their
condition before they use a systemic antifungal drug.
These drugs are not active in their natural form, but
must be converted to the active form by an acid. If
these is not enough stomach acid, the drugs will be

GALE ENCYCLOPEDIA OF MEDICINE

Ketoconazole
Ketoconazole has caused anaphylaxis (a lifethreatening allergic reaction) in some people after
their first dose. This is a rare reaction.
Systemic antifungal drugs in general
Systemic antifungal drugs may cause serious and
possibly life-threatening liver damage. Patients who
take these drugs should have liver function tests before
they start taking the medicine and as often as their
physician recommends while they are taking it. The
physician should be notified immediately if any of
these symptoms develop:


loss of appetite



nausea or vomiting



yellow skin or eyes



unusual fatigue



dark urine



pale stools
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Antifungal drugs, systemic

else that might be dangerous until they have found out
how the drugs affect them.

Antifungal drugs, topical

The most common minor side effects of systemic
antifungal drugs are constipation, diarrhea, nausea,
vomiting, headache, drowsiness, dizziness, and flushing of the face or skin. These problems usually go
away as the body adjusts to the drug and do not
require medical treatment. Less common side effects,
such as menstrual problems in women, breast enlargement in men, and decreased sexual ability in men
also may occur and do not need medical attention
unless they do not improve in a reasonable amount
of time.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with the physician who prescribed the medicine
immediately:


fever and chills



skin rash or itching



high blood pressure



pain, redness, or swelling at site of injection (for
injectable miconazole)

taking. Among the drugs that may interact with systemic antifungal drugs are:


acetaminophen (Tylenol)



birth control pills



male hormones (androgens)



female hormones (estrogens)



medicine for other types of infections



antidepressants



antihistamines



muscle relaxants



medicine for diabetes, such as tolbutamide (Orinase),
glyburide (DiaBeta), and glipizide (Glucotrol)



blood-thinning medicine, such as warfarin (Coumadin)

The list above does not include every drug that
may interact with systemic antifungal drugs. Be sure
to check with a physician or pharmacist before combining systemic antifungal drugs with any other
medicine.

Other rare side effects are possible. Anyone who
has unusual symptoms after taking systemic antifungal drugs should get in touch with his or her physician.

Interactions
Serious and possibly life-threatening side effects
can result if the oral forms of itraconazole or ketoconazole or the injectable form of miconazole are taken
with certain drugs. Do not take those types of
systemic antifungal drugs with any of the following
drugs unless the physician approves of the therapy:


astemizole (Hismanal)



cisapride (Propulsid)



antacids



theophylline-containing anti-wheezing medications

Taking an acid blocker such as cimetidine
(Tagamet), famotidine (Pepcid), nizatidine (Axid),
omeprazole (Prilosec), or ranitidine (Zantac) at the
same time as a systemic antifungal drug may prevent
the antifungal drug from working properly. For best
results, take the acid blocker at least 2 hours after
taking the antifungal drug.
In addition, systemic antifungal drugs may interact with many other medicines. When this happens,
the effects of one or both of the drugs may change or
the risk of side effects may be greater. Anyone who
takes systemic antifungal drugs should inform the prescribing physician about all other prescription and nonprescription (over-the-counter) medicines he or she is
304

Nancy Ross-Flanigan

I Antifungal drugs, topical
Definition
Topical antifungal drugs are medicines applied to
the skin to treat skin infections caused by a fungus.

Purpose
Dermatologic fungal infections are usually
described by their location on the body: tinea pedis
(infection of the foot), tinea unguium (infection of the
nails), tinia capitis (infection of the scalp.) Three types
of fungus are involved in most skin infections:
Trichophyton, Epidermophyton, and Microsporum.
Mild infections are usually susceptible to topical
therapy, however severe or resistant infections may
require systemic treatment.

Description
There are a large number of drugs currently
available in topical form for fungal infections.
Other than the imidazoles, (miconazole [Micatin,
Miconazole], clotrimazole [Lotrimin], econazole
[Spectazole], ketoconazole [Nizoral], oxiconazole
[Oxistat], sulconazole [Exelderm]) and the
GALE ENCYCLOPEDIA OF MEDICINE

Cream—A spreadable substance, similar to an ointment, but not as thick. Creams may be more appropriate than ointments for application to exposed
skin areas such as the face and hands.
Ointment—A thick, spreadable substance that
contains medicine and is meant to be used on the
skin, or if a vaginal preparation, in the vagina.
Ophthalmic—Pertaining to the eye.
Otic—Pertaining to the ear.
Topical—A term used to describe medicine that
has effects only in a specific area, not throughout
the body, particularly medicine that is put directly
on the skin.

allylamine derivatives (butenafine [Mentax], naftifine [Naftin], terbinafine [Lamisil]), the drugs in
this therapeutic class are chemically distinct from
each other. All drugs when applied topically have
a good margin of safety, and most show a high
degree of effectiveness. There are no studies comparing drugs on which to base a recommendation
for drugs of choice. Although some of the topical
antifungals are available over-the-counter, they
may be as effective as prescription drugs for this
purpose.
Traditional antifungal drugs such as undecylinic
acid (Cruex, Desenex) and gentian violet (also known
as crystal violet) remain available, but have a lower
cure rate (complete eradication of fungus) than the
newer agents and are not recommended. Tolnaftate
(Tinactin) has a lower cure rate than the newer drugs,
but may be used prophylactically to prevent
infection.

Recommended dosage
All drugs are applied topically. Consult individual
product information for specific application
recommendations.
As with all topical products, selection of the
dosage form may be as important as proper drug
selection. Consider factors such as presence or
absence of hair on the affected area, and type of
skin to which the medication is to be applied. Thin
liquids may preferable for application to hairy areas,
creams for the hands and face, and ointments may be
preferable for the trunk and legs. Other dosage forms
GALE ENCYCLOPEDIA OF MEDICINE

available include shampoos and sprays. Ciclopirox
and triacetin are available in formulations for topical
treatment of nail fungus as well as skin infections
(ciclopirox as Penlac Nail Lacquer and triacetin as
Ony-Clear Nail).
Most topical antifungal drugs require four weeks
of treatment. Infections in some areas, particularly
the spaces between toes, may take up to six weeks
for cure.

Precautions
Most topical antifungal agents are well tolerated.
The most common adverse effects are localized irritation caused by the vehicle or its components. This may
include redness, itch, and a burning sensation. Some
direct allergic reactions are possible.
Topical antifungal drugs should only be applied in
accordance with labeled uses. They are not intended or
ophthalmic (eye) or otic (ear) use. Application to
mucous membranes should be limited to appropriate
formulations.
The antifungal drugs have not been evaluated for
safety in pregnancy and lactation on topical application under the pregnancy risk category system.
Although systemic absorption is probably low, review
specific references. Gentian violet is labeled with a
warning against use in pregnancy.

Interactions
Topical antifungal drugs have no recognized
drug-drug or food-drug interactions.
Samuel D. Uretsky, PharmD

I Antigas agents
Definition
Antigas agents are medicines that relieve the
uncomfortable symptoms of too much gas in the stomach and intestines.

Purpose
Excess gas can build up in the stomach and intestines for a number of reasons. Eating high-fiber foods,
such as beans, grains, and vegetables is one cause.
Some people unconsciously swallow air when they
305

Antigas agents

KEY TERMS

Antigastroesophageal reflux drugs

KEY TERMS

preservatives, or other substances should check with
his or her physician or pharmacist before using any of
these products.

Digestive tract—The stomach, intestines, and
other parts of the body through which food passes.
Diverticulosis—A condition in which the colon
(large intestine) develops a number of outpouchings or sacs.

Anyone who has had unusual reactions to
simethicone – the active ingredient in antigas medicines – should check with his or her physician before
taking these drugs.

Flatulence—Excess gas in the digestive tract.
Irritable colon—An intestinal disorder often
accompanied by abdominal pain and diarrhea.

eat, drink, chew gum, or smoke cigarettes, which can
lead to uncomfortable amounts of gas in the digestive
system. Surgery and certain medical conditions, such
as irritable colon, peptic ulcer, and diverticulosis, can
also lead to gas build-up. Certain intestinal parasites
can contribute to the production of severe gas - these
parasites need to be treated separately with special
drugs. Abdominal pain, pressure, bloating, and flatulence are signs of too much gas. Antigas agents help
relieve the symptoms by preventing the formation of
gas pockets and breaking up gas that already is
trapped in the stomach and intestines.

Description
Antigas agents are sold as capsules, liquids, and
tablets (regular and chewable) and can be bought without a physician’s prescription. Some commonly used
brands are Gas-X, Flatulex, Mylanta Gas Relief,
Di-Gel, and Phazyme. The ingredient that helps relieve
excess gas is simethicone. Simethicone does not relieve
acid indigestion, but some products also contain antacids for that purpose. Check the label of the product or
ask the pharmacist for more information.

Recommended dosage
Check the product container for dosing information. Typically, the doses should be taken after meals
and at bedtime. Chewable forms should be chewed
thoroughly.
Check with a physician before giving this medicine to children under age 12 years.

Precautions
Some anti-gas medicines may contain sugar,
sodium, or other ingredients. Anyone who is on a
special diet or is allergic to any foods, dyes,
306

Side effects
No common or serious side effects have been
reported in people who use this medicine. However,
anyone who has unusual symptoms after taking an
antigas agent should get in touch with his or her
physician.

Interactions
Antigas agents are not known to interact with any
other drugs.
Samuel D. Uretsky, PharmD

reflux
I Antigastroesophageal
drugs
Definition
These drugs are used to treat gastroesophageal
reflux, the backward flow of stomach contents into
the esophagus.

Purpose
The drug discussed here, cisapride (Propulsid), is
used to treat nighttime heartburn resulting from gastroesophageal reflux disease (GERD). In this condition, food and stomach juices flow backward from the
stomach into the esophagus, the part of the digestive
tract through which food passes on its way from the
mouth to the stomach. Normally, a muscular ring
called the lower esophageal sphincter (LES) opens to
allow food into the stomach and then closes to prevent
the stomach’s contents from flowing back into the
esophagus. In people with GERD, this muscular ring
is either weak or it relaxes at the wrong times. The
main symptom is heartburn – a burning sensation
centered behind the breastbone and spreading upward
toward the neck and throat.
Cisapride works by strengthening the lower esophageal sphincter and making the stomach empty
GALE ENCYCLOPEDIA OF MEDICINE

Esophagus—The part of the digestive tract between
the pharynx and the stomach. (The pharynx is the
space just behind the mouth.)
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.

The effects of taking cisapride during pregnancy
have not been fully studied. Women who are pregnant or plan to become pregnant should check with
their physicians before taking Cisapride. The drug
passes into breast milk and may affect nursing
babies. Women who are breastfeeding and need to
take this medicine should check with their physicians. Avoiding breastfeeding while taking the drug
may be necessary.

Side effects
more quickly. This shortens the amount of time that the
esophagus comes in contact with the stomach contents.
Other drugs, such as H2-blockers are sometimes prescribed to reduce the amount of acid in the stomach.

Description
Cisapride is available only with a physician’s prescription. Cisapride is sold in tablet and liquid forms.

The most common side effects are abdominal
pain, bloating, gas, diarrhea, constipation, nausea,
upper respiratory infections, inflammation of the
nasal passages and sinuses, headache, and viral
infections. Other side effects may occur. Anyone
who has unusual or troublesome symptoms after
taking this drug should get in touch with his or her
physician.

Recommended dosage
The dose depends on the patient. The average
dose for adults and children age 12 and over is 5-20 mg
taken two to four times a day. The medicine should be
taken 15 minutes before meals and at bedtime. For
children under 12, the dose is based on body weight
and should be determined by the child’s physician.

Precautions
This medicine is effective in treating only nighttime heartburn, not daytime heartburn.
Cisapride may increase the effects of alcohol and
tranquilizers.
Cisapride has caused dangerous irregular heartbeats in a few people who took it with other medicines.
Anyone who takes this drug should let the physician
know all other medicines he or she is taking. Patients
with heart problems should check with their physicians before taking cisapride.
Anyone who has bleeding, blockage, or leakage in
the stomach or intestines should not take cisapride.
Cisapride should not be used by anyone who has had
an unusual reaction to the drug in the past. In addition, people with any of the following medical problems should make sure their physicians are aware of
their conditions:


Epilepsy or history of seizures



Kidney disease



Liver disease.

GALE ENCYCLOPEDIA OF MEDICINE

Interactions
Cisapride may interact with a variety of other
medicines. When this happens, the effects of one or
both of the drugs may change or the risk of side effects
may be greater. Anyone who takes Cisapride should
let the physician know all other medicines he or she is
taking. Among the drugs that may interact with cisapride are:


Antifungal drugs such as ketoconazole (Nizoral),
miconazole (Monistat), and fluconazole (Diflucan)



Antibiotics such as clarithromycin (Biaxin) and erythromycin (E-Mycin, ERYC)



Blood-thinners such as warfarin (Coumadin)



H2-blockers such as cimetidine (Tagamet) and ranitidine (Zantac)



Tranquilizers such as chlordiazepoxide (Librium),
diazepam (Valium), and alprazolam (Xanax).

The list above does not include every drug that
may interact with cisapride. Be sure to check with a
physician or pharmacist before combining cisapride
with any other prescription or nonprescription (overthe-counter) medicine.
Resources
ORGANIZATIONS

National Digestive Diseases Information Clearinghouse. 2
Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.
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Antigastroesophageal reflux drugs

KEY TERMS

Antihelminthic drugs

Pediatric/Adolescent Gastroesophageal Reflux Association,
Inc. P.O. Box 1153, Germantown, MD 20875-1153.
(301) 601-9541. <http://www.reflux.org>.
OTHER

‘‘GERD Information Center.’’ Pharmaceutical Information
Network. <http://pharminfo.com/disease/gerd/
gerd_info.html>.
GERD Information Resource Center. <http://
www.gerd.com>.

Nancy Ross-Flanigan

I Antihelminthic drugs
Definition
Antihelminthic drugs are used to treat parasitic
infestations.

Purpose
Parasitic infestations are caused by protozoa or
worms gaining entry into the body. Most of these
organisms cause infections by being ingested in the
form of eggs or larvae, usually present on contaminated
food or clothing, while others gain entry through skin
abrasions. Common parasitic infestations include amebiasis, malaria, giardiasis, hookworm, pinworm,
threadworm, whipworm and tapeworm infestations.
Once in the body, parasitic worms may go unnoticed
if they cause no severe symptoms. However, if they
multiply rapidly and spread to a major organ, they
can cause very serious and even life-threatening conditions. Antihelminthic drugs are prescribed to treat these
infestations. They function either by destroying the
worms on contact or by paralyzing them, or by altering
the permeability of their plasma membranes. The dead
worms then pass out of the body in the feces.

Description
Antihelminthic drugs are available only with a
prescription and are available as liquids, tablets or capsules. Some commonly used antihelminthics include:
albendazole (Albenza), mebendazole (Vermox), niclosamide (Niclocide), oxamniquine (Vansil), praziquantel
(Biltricide), pyrantel (Antiminth), pyantel pamoate
(Antiminth) and thiabendazole (Mintezol). Some types
of parasitic infestations are rarely seen in the United
States, thus, the corresponding antihelminthic drugs are
not widely distributed and need to be obtained from the
308

United States Center for Disease Control (CDC) when
required. These include for example bitional and ivermectin, used to treat onchocerciasis infestations. Other
antihelminthic drugs, such as diethylcarbamazepine
citrate (Hetrezan), used for treatment of roundworms
and other parasites, is supplied directly by its manufacturer when needed.
Most antihelminthic drugs are only active against
specific parasites, some are also toxic. Before treatment, the parasites must therefore be identified using
tests that look for parasites, eggs or larvae in feces,
urine, blood, sputum, or tissues. Thus, niclosamide is
used against tapeworms, but will not be effective for
the treatment of pinworm or roundworm infestations,
because it acts by inhibiting ATP production in tapeworm cells. Thiabendazole (Mintezole) is the drug
usually prescribed for treatment of threadworm, but
a similar drug, mebendazole (Vermox) works better on
whipworm by disrupting the microtubules of this
worm. Praziquantel is another drug that acts by altering the membrane permeability of the worms.

Preparation
Dosage is established depending on the patient’s
general health status and age, the type of antihelminthic drug used, and the type of parasitic infestation
being treated. The number of doses per day, the time
between doses, and the length of treatment will also
depend on these factors.
Antihelminthic drugs must be taken exactly as
directed to completely rid the body of the parasitic
infestation, and for as long as directed. A second
round of treatment may be required to ensure that
the infection has completely cleared.

Precautions
Some antihelminthic drugs work best when ingested
along with fatty foods, such as milk or ice cream. Oral
drugs should be taken with water during or after meals.
The prescribing physician should be informed if the
patient has a low-fat or other special diet.
Some antihelminthic drugs, such as praziquantel,
come in chewable form. These tablets should not be
chewed or kept in the mouth, but should swallowed
whole because their bitter taste may cause gagging or
vomiting.
Antihelminthic drugs sometimes need to be taken
with other medications. For example, steroids such as
prednisone are also prescribed together with the antihelminthic drug for tapeworm to reduce the inflammation that the worm may cause.
GALE ENCYCLOPEDIA OF MEDICINE

Amebiasis—Parasitic infestation caused by amebas,
especially by Entamoeba histolytica.
Colitis—Inflammation of the colon (large intestine).
Feces—The solid waste that is left after digestion.
Feces form in the intestines and leave the body
through the anus.
Flukes—Parasite worms that look like leeches. They
usually have one or more suckers for attaching to the
digestive mucosa of the host. Liver flukes infest the
liver, destroying liver tissue and impairing bile production and drainage.
Giardiasis—Parasitic infestation caused by a flagellate protozoan of the genus Giardia, especially by
G. lamblia.
Hallucination—A false or distorted perception of
objective reality. Imaginary objects, sounds, and
events are perceived as real.
Hookworm—Parasitic intestinal infestation caused
by any of several parasitic nematode worms of the
family Ancylostomatidae. These worms have strong
buccal hooks that attach to the host’s intestinal
lining.
Larva—The immature, early form of an organism
that at birth or hatching is not like its parent and
has to undergo metamorphosis before assuming
adult features.
Malaria—Disease caused by the presence of
sporozoan parasites of the genus Plasmodium in
the red blood cells, transmitted by the bite
of anopheline mosquitoes, and characterized
by severe and recurring attacks of chills and
fever).
Microtubules—Slender,
channels in worms.

elongated

Parasite—An organism that lives in or with another
organism, called the host, in parasitism, a type of
association characterized by the parasite obtaining
benefits from the host, such as food, and the host
being injured as a result.
Parasitic—Of, or relating to a parasite.
Pinworm—Enterobius vermicularis, a nematode
worm of the family Oxyuridae that causes parasitic infestation of the intestines and cecum.
Pinworm is endemic in both temperate and tropical regions and common especially in school
age children.
Onchocerciasis—Parasitic infestation caused by
filamentous worms of the genus Onchocerca,
especially O. volvulus, that is found in tropical
America and is transmitted by several types of
blackflies.
Protozoan—Any unicellular or multicellular organism containing nuclei and organelles (eukaryotic) of
the subkingdom Protozoa.
Roundworm—Any round-bodied unsegmented
worm as distinguished from a flatworm. Also called
a nematode, they look similar to the common
earthworm.
Tapeworm—Flat and very long (up to 30 meters)
intestinal parasitic worms, similar to a long piece of
tape. Common tapeworms include: T. saginata (beef
tapeworm), T. solium (pork tapeworm) D. latum (fish
tapeworm), H. Nana (dwarf tapeworm) and E. granulosus (dog tapeworm). General symptoms are
vague abdominal discomfort, nausea, vomiting,
diarrhea and weight loss.
Threadworm—Any long, thin nematode worm.

anatomical

Trematode—Any parasitic flatworm of the class
Trematoda, as the liver fluke.

Nematode—Roundworm.
Organism—A single, independent life form, such as
a bacterium, a plant or an animal.

Whipworm—A nematode worm of the family
Trichuridae with a body that is thick at one end and
very long and slender at the other end.

When required, pre- or post-treatment purges are
also performed with magnesium or sodium sulfate.

Hookworm or whipworm infections are also treated with iron supplements along with the antihelminthic prescription.

Regular medical visits are recommended for people affected by parasitic infestations. The physician
monitors whether the infection is clearing or not and
also keeps track of unwanted side effects. The prescribing physician should be informed if symptoms
do not disappear or if they get worse.
GALE ENCYCLOPEDIA OF MEDICINE

Some types of parasitic infestations (e.g. pinworms) can be passed from one person to another. It
is then often recommended that everyone in the household of an infected person be asked to also take the
prescribed antihelminthic drug.
309

Antihelminthic drugs

KEY TERMS

Antihemorrhoid drugs

Risks
People with the following medical conditions may
have adverse reactions to antihelminthic drugs. The
prescribing physician should accordingly be informed
if any of these conditions are present:


Allergies. Anyone who has had adverse reactions to
antihelminthic drugs should inform the prescribing
physician before taking the drugs again. The physician should also be informed about any other preexisting allergies.



Ulcers. Antihelminthic drugs are also contraindicated for persons diagnosed with ulcers of the digestive tract, especially ulcerative colitis.



Pregnancy. There is research evidence reporting that
some antihelminthic drugs cause birth defects or miscarriage in animal studies. No human birth defects
have been reported, but antihelminthic drugs are
usually not recommended for use during pregnancy.
Pregnant women should accordingly inform the prescribing physician.





Breastfeeding. Some antihelminthic drugs can pass
into breast milk. Breastfeeding may have to be discontinued until the antihelminthic treatment has
ended and breastfeeding mothers must also inform
the prescribing physician.
Other risk conditions. Any of the following medical
conditions should also be reported to the prescribing
physician: Crohn’s disease, liver disease, kidney disease and worm cysts in the eyes.

Common side effects of antihelminthic drugs
include dizziness, drowsiness, headache, sweating, dryness of the mouth and eyes, and ringing in the ears.
Anyone taking these drugs should accordingly avoid
driving, operating machines or other activities that
may be dangerous until they know how they are
affected by the drugs. Side effects usually wear off as
the body adjusts to the drug and do not usually require
medical treatment. Thiabendazole may cause the urine
to have an unusual odor that can last for a day after
the last dose. Other side effects of antihelminthic
drugs, such as loss of appetite, diarrhea, nausea, vomiting, or abdominal cramps are less common. If they
occur, they are usually mild and do not require medical attention.
More serious side effects, such as fever, chills,
confusion, extreme weakness, hallucinations, severe
diarrhea, nausea or vomiting, skin rashes, low back
pain, dark urine, blurred vision, seizures, and jaundice
have been reported in some cases. The patient’s physician should be informed immediately if any should
develop. As a rule, anyone who has unusual symptoms
310

after starting treatment with antihelminthic drugs
should notify the prescribing physician.
Antihelminthic drugs may interact with each
other or with other drugs, whether prescribed or not.
For example, it has been reported that use of the
antihelminthic drugs pyrantel and piperazine together
lowers the efficiency of pyrantel. Similarly, combining
a given antihelminthic drug with another medication
may increase the risk of side effects from either drug.
Nancy Ross-Flanigan

I Antihemorrhoid drugs
Definition
Antihemorrhoid drugs are medicines that reduce
the swelling and relieve the discomfort of hemorrhoids
(swellings in the area around the anus).

Purpose
Hemorrhoids are bulges in the veins that supply
blood to the skin and membranes of the area around
the anus. They may form for various reasons.
Frequent heavy lifting, sitting for long periods, or
straining to have bowel movements may put stress
on anal tissues, which can lead to hemorrhoids.
Some women develop hemorrhoids during pregnancy
as the expanding uterus puts pressure on the anal
tissues. The strain of labor and delivery can also
cause hemorrhoids or make existing hemorrhoids
worse. Hemorrhoids sometimes result from certain
medical problems, such as tumors pressing on the
lower bowel.
The main symptoms of hemorrhoids are bleeding
from the rectum, especially after a bowel movement,
and itching, burning, pain, and general discomfort in
the anal area. Over-the-counter antihemorrhoid products can relieve many of these symptoms. The products contain combinations of four main types of
ingredients:


Local anesthetics, such as benzocaine, lidocaine and
tetracaine, to temporarily relieve the pain



Vasoconstrictors, such as epinephrine base, epinephrine hydrochloride, ephedrine sulfate and phenylephrine hydrochloride that reduce swelling and relieve
itching and discomfort by tightening blood vessels



Astringents (drying agents), such as witch hazel, calamine, and zinc oxide. These help shrink hemorrhoids
GALE ENCYCLOPEDIA OF MEDICINE

Anus—The opening at the end of the intestine
through which solid waste (stool) passes as it leaves
the body.
Rectum—The end of the intestine closest to the
anus.
Uterus—A hollow organ in a female in which a
fetus develops until birth.

phenelzine (Nardil) or tranylcypromine (Parnate),
used to treat conditions including depression and
Parkinson’s disease. Anyone who is not sure if he or
she has taken this type of drug should check with a
physician or pharmacist before using an antihemorrhoid drug. People who are taking antidepressants or
medicine for high blood pressure also should not use
certain antihemorrhoid drugs. Check with a pharmacist for a list of drugs that may interact with specific
antihemorrhoid drugs.
Nancy Ross-Flanigan

by pulling water out of the swollen tissue. This, in
turn, helps relieve itching, burning, and irritation.


Protectants, such as cocoa butter, lanolin, glycerin,
mineral oil, and shark liver oil which soothe irritated
tissues and form a protective barrier to prevent
further irritation.

Description
Antihemorrhoid drugs are available as creams,
ointments and suppositories. Most can be bought
without a physician’s prescription.

Recommended dosage
Follow package instructions for using these products. Do not use more than the recommended
amount of this medicine every day. For explanations
or further information about how to use antihemorrhoid drugs, check with a physician or pharmacist.

Precautions
Do not use antihemorrhoid drugs for more than
seven days in a row. If the problem gets worse or does
not improve, check with a physician.
If rectal bleeding continues, check with a physician. This could be a sign of a condition that needs
medical attention.

Side effects
Side effects are rare, however, if a rash or any
other sign of an allergic reaction occurs, stop using
the medicine.

Interactions
Some antihemorrhoid drugs should not be used
by people who are taking or have recently taken monoamine oxidase inhibitors (MAO inhibitors), such as
GALE ENCYCLOPEDIA OF MEDICINE

I Antihistamines
Definition
Antihistamines are drugs that block the action of
histamine (a compound released in allergic inflammatory reactions) at the H1 receptor sites, responsible for
immediate hypersensitivity reactions such as sneezing
and itching. Members of this class of drugs may also be
used for their side effects, including sedation and antiemesis (prevention of nausea and vomiting).

Purpose
Antihistamines provide their primary action by
blocking histamine H1 at the receptor site. They have
no effect on rate of histamine release, nor do they
inactivate histamine. By inhibiting the activity of
histamine, they can reduce capillary fragility, which
produces the erythema, or redness, associated with
allergic reactions. They will also reduce histamineinduced secretions, including excessive tears and
salivation. Additional effects vary with the individual drug used. Several of the older drugs, called
first-generation antihistamines, bind non-selectively
to H1 receptors in the central nervous system as
well as to peripheral receptors, and can produce
sedation, inhibition of nausea and vomiting, and
reduction of motion sickness. The second-generation
antihistamines bind only to peripheral H1 receptors,
and reduce allergic response with little or no
sedation.
The first-generation antihistamines may be
divided into several chemical classes. The side effect
profile, which also determines the uses of the drugs,
will vary by chemical class. The alkylamines include
brompheniramine (Dimetapp) and chlorpheniramine
311

Antihistamines

KEY TERMS

Antihistamines

D A N I E L E B O V E T (1907–1992)
A gifted researcher in therapeutic chemistry,
Daniele Bovet was born in Neuchatel, Switzerland, one
of four children of a professor of experimental education.
Bovet studied zoology and comparative anatomy at the
University of Geneva, receiving his doctor of science
degree in 1929. He then joined the Pasteur Institute in
Paris, becoming director of the Laboratory of Therapeutic
Chemistry in 1936.
Bovet investigated histamine, thought to cause
allergy symptoms. No antagonist of histamine was
known, so Bovet—with his research student Anne-Marie
Staub—began studying substances that blocked hormones
similar to histamine. By 1937 he had produced the first
antihistamine, thymoxydiethylamine. Since this substance
was too toxic for human use, Bovet and Staub performed
thousands more experiments seeking less toxic antihistamines. This work formed the basis for the development of
subsequent clinically useful antihistamines.

is a phenothiazine, chemically related to the major
tranquilizers, and while it is used for treatment of allergies, may also be used as a sedative, the relieve anxiety
prior to surgery, as an anti-nauseant, and for control of
motion sickness. Diphenhydramine (Benadryl) is chemically an ethanolamine, and in addition to its role in
reducing allergic reactions, may be used as a nighttime
sedative, for control of drug-induced Parkinsonism,
and, in liquid form, for control of coughs. Consult
more detailed references for further information.
The second generation antihistamines have no
central action, and are used only for treatment of
allergic reactions. These are divided into two chemical
classes. Cetirizine (Zyrtec) is a piperazine derivative,
and has a slight sedative effect. Loratidine (Claritin)
and fexofenadine (Allegra) are members of the piperadine class and are essentially non-sedating.

Recommended dosage
Dosage varies with drug, patient and intended
use. Consult more detailed references for further
information.

ANTIHISTAMINES

Brand Name (Generic Name)
*Atarax (hydroxyzine
hydrochloride)
Benadryl (diphenhydramine
hydrochloride)
Hismanal (astemiozole)
PBZ-SR (tripelennamine
hydrochloride)
Periactin (cyproheptadine
hydrochloride)
Phenergan (promethazine
hydrochloride)
Polaramine (dexchlorpheniramine maleate)
Seldane, Seldane-D
(terfenadine)
Tavist (clemastine fumarate)
Trinalin Repetabs (azatadine
maleate, pseudoephedrine
sulfate)

Possible Common Side Effects
Include:
Drowsiness, dry mouth
Dizziness, sleepiness, upset stomach,
decreased coordination
Drowsiness, dry mouth, fatigue, weight
gain
Dizziness, drowsiness, dry mouth and
throat, chest congestion, decreased
coordination, upset stomach
Chest congestion, dizziness, fluttery
heartbeat, loss of appetite, hives, sleepiness, vision problems
Changes in blood pressure, dizziness,
blurred vision, nausea, rash
Drowiness
Upset stomach, nausea, drowiness,
headache, fatigue
Decreased coordination, dizziness,
upset stomach
Abdominal cramps, chest pain, dry
mouth, headache

*Also used in the treatment of
anxiety

(Chlor-Trimeton.) These agents cause relatively little
sedation, and are used primarily for treatment of allergic reactions. Promethazine (Phenergan), in contrast,
312

When used for control of allergic reactions, antihistamines should be taken on a regular schedule,
rather than on an as-needed basis, since they have no
effect on histamine itself, nor on histamine already
bound to the receptor site.
Efficacy is highly variable from patient to patient. If
an antihistamine fails to provide adequate relief, switch
to a drug from a different chemical class. Individual
drugs may be effective in no more than 40% of patients,
and provide 50% relief of allergic symptoms.

Side effects
The frequency and severity of adverse effects will
vary between drugs. Not all adverse reactions will
apply to every member of this class.
Central nervous system reactions include drowsiness,
sedation, dizziness, faintness, disturbed coordination, lassitude,confusion, restlessness,excitation,tremor,seizures,
headache, insomnia, euphoria, blurred vision, hallucinations, disorientation, disturbing dreams/nightmares, schizophrenic-like reactions, weakness, vertigo, hysteria,
nerve pain, and convulsions. Overdoses may cause involuntary movements. Other problems have been reported.
Gastrointestinal problems include increased
appetite, decreased appetite, nausea, vomiting, diarrhea, and constipation.
Hematologic reactions are rare, but may be
severe. These include anemia, or breakdown of red
GALE ENCYCLOPEDIA OF MEDICINE

glaucoma



hyperthyroidism (overactive thyroid)

Allergen—A substance that causes an allergy.



high blood pressure

Anaphylaxis—A sudden, life-threatening allergic
reaction.



enlarged prostate



heart disease



ulcers or other stomach problems



stomach or intestinal blockage



liver disease



kidney disease



bladder obstruction



diabetes

Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Histamine—A chemical released from cells in the
immune system as part of an allergic reaction.
Pregnancy category— A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B:
Animal studies indicate no fetal risk, but no
human studies; or adverse effects in animals, but
not in well-controlled human studies. Category C:
No adequate human or animal studies; or adverse
fetal effects in animal studies, but no available
human data. Category D: Evidence of fetal risk,
but benefits outweigh risks. Category X: Evidence
of fetal risk. Risks outweigh any benefits.

Antihypertensive drugs



KEY TERMS

Interactions
Monoamine oxidase inhibitor antidepressants
(phenelzine [Nardil], tranylcypromine [Parnate]) may
prolong and increase the effects of some antihistamines. When used with promethazine (Phenergan)
this may cause reduced blood pressure and involuntary movements.
Resources
ORGANIZATIONS

blood cells; reduced platelets; reduced white cells; and
bone marrow failure.
A large number of additional reactions have been
reported. Not all apply to every drug, and some reactions may not be drug related. Some of the other adverse
effects are chest tightness; wheezing; nasal stuffiness; dry
mouth, nose and throat; sore throat; respiratory depression; sneezing; and a burning sensation in the nose.
When taking antihistamines during pregnancy,
Chlorpheniramine (Chlor-Trimeton), dexchlorpheniramine (Polaramine), diphenhydramine (Benadryl),
brompheniramine (Dimetapp), cetirizine (Zyrtec),
cyproheptadine (Periactin), clemastine (Tavist), azatadine (Optimine), loratadine (Claritin) are all listed
as category B. Azelastine (Astelin), hydroxyzine
(Atarax), promethazine (Phenergan) are category C.
Regardless of chemical class of the drug, it is
recommended that mothers not breast feed while
taking antihistamines.
Contraindications
The following are absolute or relative contraindications to use of antihistamines. The significance of
the contraindication will vary with the drug and dose.
GALE ENCYCLOPEDIA OF MEDICINE

Allergy and Asthma Network. 3554 Chain Bridge Road,
Suite 200. (800) 878-4403.
American Academy of Allergy, Asthma, and Immunology.
611 East Wells St, Milwaukee, WI 53202. (800) 8222762. <http://www.aaaai.org>.
Asthma and Allergy Foundation of America. 1125 15th
Street NW, Suite 502, Washington, DC 20005.
(800)727-8462.

Samuel D. Uretsky, PharmD

Antihyperlipidemic drugs see Cholesterolreducing drugs

I Antihypertensive drugs
Definition
Antihypertensive drugs are medicines that help
lower blood pressure.

Purpose
The overall class of antihypertensive agents lowers
blood pressure, although the mechanisms of action vary
greatly. In 2003, a Joint National Committee on
313

Antihypertensive drugs

Antihypertensive Drugs (continued)

Antihypertensive Drugs

Brand Name (Generic
Name)
Accupril (quinapril
hydrochloride)
Aldatazide
Aldactone
(spironolactone)
Aldomet (methyldopa)
Altace (ramipril)
Calan, Calan SR (verapamil hydrochloride)
Capoten (captopril)
Cardene (nicardipine
Hydrochloride)
Cardizem (diltiazem
hydrochloride)
Cardura (doxazosin
mesylate)
Catapres
Corgard (nadolol)
Corzide
Diuril (chlorothiazide)
Dyazide
DynaCirc (isradipine)
HydroDIURIL
(hydrochlorothiazide)
Hygroton
(chlorthalidone)
Hytrin (terazosin
hydrochloride)
Inderal (propranolol
hydrochloride)
Inderide
Lasix (furosemide)
Lopressor (metoprolol
tartrate)
Lotensin (benazepril
hydrochloride)
Alozol (indapamide)
Maxzide
Minipress (prazosin
hdrochloride)
Moduretic
Monopril (fosinopril
sodium)
Normodyne (labetalol
hydrochloride)
Plendil (felodipine)

Procardia, Procardia X
(nifedipine)
Sectral (acebutolol
hydrochloride)
Ser-Ap-Es
Tenex (guanfacine
hydrochloride)
Tenoretic
Tenormin (atenolol)
Veseretic

314

Possible Common Side Effects Include:
Headache, dizziness
Diarrhea, fever, headache, decreased
coordination
Cramps, drowsiness, stomach disorders
Fluid retention, headache, weak feeling
Headache, cough
Constipation, fatigue, decreased blood
pressure
Decreased sense of taste, decreased blood
pressure tiching, rash
Dizziness, headache, indigestion and nausea,
increased heartbeat
Dizziness, fluid retention, headache, nausea,
skin rash
Dizziness, fatigue, drowsiness, headache
Dry mouth, drowsiness, dizziness, constipation
Behaviorial changes, dizziness, decreased
heartbeat, tiredness
Dizziness, decreased heartbeat, fatigue, cold
hands and feet
Cramps, constipation or diarrhea, dizziness,
fever, increased glocose level in urine
Blurred vision, muscle and abdominal pain,
fatigue
Chest pain, fluid retention, headache, fatigue
Upset stomach, headache, cramps, loss of
appetite
Anemia, constipation or diarrhea, cramps,
itching
Dizziness, labored breathing, nausea, swelling
Constipation or diarrhea, tingling sensation,
nausea and vomiting
Blurred vision, cramps, fatigue, loss of appetite
Back and muscle pain, indigestion, nausea
Diarrhea, itching/rash, tiredness
Nausea, dizziness, fatigue, headache
Anxiety, headache, loss of energy, muscle
cramps
Cramps, labored breathing, drowsiness,
irritated stomach
Headache, nausea, weakness, dizziness
Diarrhea, fatigue, itching, loss of appetite
Nausea and vomiting, headache, cough
Fatigue, nausea, stuffy nose
Pain in back, chest, muscles, joints, and
abdomen, itching, dry mouth, respiratory
problems
Swelling, constipation, decreased blood
pressure, nausea, fatigue
Constipation or diarrhea, gas, chest and joint
pain
Blurred vision, cramps, muscle pain, dizziness
Headache, constipation, dry mouth, weakness
Decreased heartbeat, fatigue, nausea
Nausea, fatigue, dizziness
Diarrhea, muscle cramps, rash

Brand Name (Generic
Name)
Vasotec (enalapril
maleate)
Visken (pindolol)
Wytensin (guanabenz
acetate)
Zaroxolyn (metolazone)
Zestoretic (lisinopril
hydrochlorothiazide)
Zestril (lisinopril)

Possible Common Side Effects Include:
Chest pain, blurred vision, constipation or diarrhea, hives, nausea
Muscle cramps, labored breathing, nausea, fluid
retention
Headache, drowsiness, dizziness
Constipation or diarrhea, chest pain, spasms,
nausea
Fatigue, headache, dizziness
Labored breathing, abdominal and chest pain,
nausea, decreased blood pressure

Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure report said that recent clinical trials
show that antihypertensive treatment can reduce incidence of stroke by 35-40%, heart attack by 20-25%,
and onset of new heart failure by 50%. Within this therapeutic class, there are several subgroups of drugs. There
are a large number of drugs used to control hypertension,
and the drugs listed below are representative, but not the
only members of their classes.
The calcium channel blocking agents, also called
slow channel blockers or calcium antagonists, inhibit
the movement of ionic calcium across the cell membrane.
This reduces the force of contraction of muscles of the
heart and arteries. Although the calcium channel blockers
are treated as a group, there are four different chemical
classes, leading to significant variations in the activity of
individual drugs. Nifedipine (Adalat, Procardia) has the
greatest effect on the blood vessels, while verapamil
(Calan, Isoptin) and diltiazem (Cardizem) have a greater
effect on the heart muscle itself.
Peripheral vasodilators such as hydralazine
(Apresoline), isoxuprine (Vasodilan), and minoxidil
(Loniten) act by relaxing blood vessels.
There are several groups of drugs that act by
reducing adrenergic nerve stimulation, the excitatory
nerve stimulation that causes contraction of the muscles in the arteries, veins, and heart. These drugs
include the beta-adrenergic blockers and alpha/beta
adrenergic blockers. There are also non-specific adrenergic blocking agents.
Beta-adrenergic blocking agents include propranolol (Inderal), atenolol (Tenormin), and pindolol
(Visken). Propranolol acts on the beta-adrenergic
receptors anywhere in the body, and has been used as
a treatment for emotional anxiety and rapid heart
GALE ENCYCLOPEDIA OF MEDICINE

Adrenergic—Activated by adrenalin (norepinephrine), loosely applied to the sympathetic nervous
system responses.
Angioedema—An allergic skin disease characterized by patches of confined swelling involving the
skin the layers beneath the skin, the mucous membranes, and sometimes the viscera—called also
angioneurotic edema, giant urticaria, Quincke’s
disease, or Quincke’s edema.
Arteries—Blood vessels that carry blood away from
the heart to the cells, tissues, and organs of the body.
Laryngospasm —Spasmodic closure of the larynx.
Pregnancy category—A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B: Animal
studies indicate no fetal risk, but no human studies;
or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate
human or animal studies; or adverse fetal effects in
animal studies, but no available human data.
Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks
outweigh any benefits.
Sympathetic nervous system—The part of the autonomic nervous system that is concerned especially
with preparing the body to react to situations of
stress or emergency; it contains chiefly adrenergic
fibers and tends to depress secretion, decrease the
tone and contractility of smooth muscle, and
increase heart rate.

beat. Atenolol and acebutolol (Sectral) act specifically
on the nerves of the heart and circulation.
There are two alpha/beta adrenergic blockers,
labetolol (Normodyne, Trandate) and carvedilol
(Coreg). These work similarly to the beta blockers.
The ACE II inhibitors, losartan (Cozaar), candesartan (Atacand), irbesartan (Avapro), telmisartan
(Micardis), valsartan (Diovan) and eprosartan
(Teveten) directly inhibit the effects of ACE II rather
than blocking its production. Their actions are similar
to the ACE inhibitors, but they appear to have a more
favorable side effect and safety profile.
In addition to these drugs, other classes of drugs
have been used to lower blood pressure, most
GALE ENCYCLOPEDIA OF MEDICINE

notably the thiazide diuretics. There are 12 thiazide
diuretics marketed in the United States, including
hydrochlorothiazide (Hydrodiuril, Esidrex), indapamide (Lozol), polythiazide (Renese), and hydroflumethiazide (Diucardin). The drugs in this class
appear to lower blood pressure through several
mechanisms. By promoting sodium loss they lower
blood volume. At the same time, the pressure of the
walls of blood vessels, the peripheral vascular resistance, is lowered. Thiazide diuretics are commonly
used as the first choice for reduction of mild hypertension, and may be used in combination with other
antihypertensive drugs.
Debate continued in 2003 as to the best drugs to
lower blood pressure. One study seemed to prove
that diuretics were the best initial choice, but a
study from Australia said that ACE inhibitors
were a superior choice. However, many physicians
agreed that the best treatment for a particular
patient depends on his or her particular age, economic situation, genetic factors and other existing
illnesses and conditions.
While designed to lower cholesterol rather than
blood pressure, a large clinical trial reported in 2003
that people with high blood pressure may one day
benefit from taking them. In the trial, participants
with increased risk for heart disease, even if it was not
from high cholesterol, benefited from taking statins.

Recommended dosage
Recommended dosage varies with patient, drug,
severity of hypertension, and whether the drug is being
used alone or in combination with other drugs.
Specialized references can be consulted for further
information.

Precautions
Because of the large number of classes and individual drugs in this group, specialized references offer
more complete information.
Peripheral vasodilators may cause dizziness and
orthostatic hypotension—a rapid lowering of blood
pressure when the patient stands up in the morning.
Patients taking these drugs must be instructed to rise
from bed slowly. Pregnancy risk factors for this group
are generally category C. Hydralazine has been shown to
cause cleft palate in animal studies, but there is no human
data available. Breastfeeding is not recommended.
ACE inhibitors generally are well tolerated, but
rarely may cause dangerous reactions including laryngospasm and angioedema. Persistent cough is a
315

Antihypertensive drugs

KEY TERMS

Anti-hyperuricemic drugs

common side effect. ACE inhibitors should not be
used in pregnancy. When used in pregnancy during
the second and third trimesters, angiotension-converting inhibitors (ACEIs) can cause injury to and even
death in the developing fetus. When pregnancy is
detected, discontinue the ACE inhibitor as soon as
possible. Breastfeeding is not recommended.
ACE II inhibitors are generally well tolerated and
do not cause cough. Pregnancy risk factor is category C
during the first trimester and category D during the
second and third trimesters. Drugs that act directly on
the renin-angiotensin system can cause fetal and
neonatal morbidity and death when administered to
pregnant women. Several dozen cases have been
reported in patients who were taking ACE inhibitors.
When pregnancy is detected, AIIRAs should be discontinued as soon as possible. Breastfeeding is not
recommended.
Thiazide diuretics commonly cause potassium
depletion. Patients should have potassium supplementation either through diet or potassium supplements.
Pregnancy risk factor is category B (chlorothiazide,
chlorthalidone, hydrochlorothiazide, indapamide,
metolazone)
or
category
C
(bendroflumethiazide, benzthiazide, hydroflumethiazide, methyclothiazide, trichlormethiazide). Routine use during
normal pregnancy is inappropriate. Thiazides are
found in breast milk. Breastfeeding is not recommended.
Beta blockers may cause a large number of adverse
reactions including dangerous heart rate abnormalities.
Pregnancy risk factor is category B (acebutolol, pindolol, sotalol) or category C (atenolol, labetalol, esmolol,
metoprolol, nadolol, timolol, propranolol, penbutolol,
carteolol, bisoprolol). Breastfeeding is not recommended. In 2003, a report announced that adavances in
pharmacogenetics mean that in the future, physicians
may be able to use a patients genetic information to
make certain prescribing decisions for antihypertensives.

Interactions
Specific drug references should be consulted, since
interactions vary for antihypertensive drugs.
Resources
PERIODICALS

Belden, Heidi. ‘‘Debate Continues Over Best Drug for
Hypertension.’’ Drug Topics (April 21, 2003): 32.
Mechcatie, Elizabeth. ‘‘Genetics Will Guide Prescribing for
Hypertension: Genotype Predicts Response to Drug.’’
Internal Medicine News (July 1, 2003): 48-51.
‘‘New Hypertension Guidelines: JNC-7.’’ Clinical
Cardiology Alert (July 2003): 54-63.
316

‘‘Studies Show ThatáStatins Benefits People With High
Blood Pressure.’’ Harvard Health Letter (June 2003).

Samuel D. Uretsky, PharmD
Teresa G. Odle

I Anti-hyperuricemic drugs
Definition
Anti-hyperuricemic drugs are used to treat hyperuricemia, the state of having too much uric acid in the
blood.

Purpose
Anti-hyperuricemic drugs decrease the levels
of uric acid in the blood, either by increasing
the rate at which uric acid is excreted in the
urine, or by preventing the formation of excess
uric acid.

Precautions
Before taking any medication, patients should
notify their physician of all other medications that
they are currently taking. Patients should also notify
their physician of any health problems they are currently experiencing. Patients must notify physicians if
they have kidney problems, since this might affect the
type of drug administered. Patients must also notify
their physician if they are allergic to any of the medications used to treat acute or long-term gout. Since all
of these factors contribute to the disease, patients
suffering from gout should attempt to lose weight,
avoid excess alcohol consumption, and avoid foods
high in purines, such as asparagus, sardines, lobster,
avocado, and peas.

Description
Gout and hyperuricemia
Persons with high levels of uric acid (hyperuricemia) may experience gout. Commonly gout occurs in
males in their 40s and 50s. Gout is defined by the
attacks of (arthritic) painful, reddened joints, and is
often accompanied by hard lumps in the painful joints.
The most common joint affected is the big toe. Kidney
stones, and/or poor kidney function may also be associated with hyperuricemia, but may not be considered
gout if the patient does not have painful joints. In
persons with gout (and associated symptoms), uric
GALE ENCYCLOPEDIA OF MEDICINE

Acute gout attacks
When patients experience acute attacks of
gout, drugs that lower the levels of uric acid can
cause an acute gout attack or cause an attack to
become more severe. Thus, drugs that lower uric
acid levels and are used to treat gout in the long
term are not used in the short term. Medications
used in acute gout attacks include non-steroidal
anti-inflammatory drugs (such as indomethacin),
colchicine, and corticosteroids. Colchicine causes
side effects in a large number of individuals
(usually diarhhea). The most important factor in
the effective treatment of gout may not be the drug
used, but how quickly it is administered after an
acute attack has begun.
Long-term treatment
Long-term treatment of gout or hyperuricemia
usually involves one of four drugs: allopurinol,
probenicid, sulphinpyrazone, or benzbromarone
(as of 2001, benzbromarone was not available for
use in the United States). While allopurinol
decreases the amount of uric acid that is produced
(and may help prevent acute attacks of gout), the
other drugs all increase the rate at which uric acid
is excreted in the urine. As previously mentioned,
lowering the concentration of uric acid can cause
gout attacks. Thus, patients taking these medications should have the dose slowly increased (and
uric acid levels slowly lowered) to prevent acute
attacks of gout. Patients may also be treated with
colchicine or non-steroidal anti-inflammatory
drugs to prevent acute attacks of gout (corticosteroids are not used in this scenario because over the
long term corticosteroids have deleterious side
effects). In 2004, the FDA was seeking trial data
on a new drug called oxypurinol (Oxyprim) for
treating chronic gout. These medications may
have to be taken for life to prevent further gout
attacks.
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

Coghill, Kim. ‘‘FDA Panel Discusses Endpoints for Approval
of Gout Products.’’ Bioworld Today June 3, 2004.

Michael V Zuck, PhD
Teresa G. Odle

I Anti-insomnia drugs
Definition
Anti-insomnia drugs are medicines that help
people fall asleep or stay asleep.

Purpose
Physicians prescribe anti-insomnia drugs for shortterm treatment of insomnia—a sleep problem in which
people have trouble falling asleep or staying asleep or
wake up too early and can’t go back to sleep. These drugs
should be used only for occasional treatment of temporary sleep problems and should not be taken for more than
a week or two at a time. People whose sleep problems last
longer than this should see a physician. Their sleep problems could be a sign of another medical problem.

Description
The anti-insomnia drug described here, zolpidem
(Ambien), is a classified as a central nervous system
(CNS) depressant. CNS depressants are medicines
that slow the nervous system. Physicians also prescribe
medicines in the benzodiazepine family, such as flurazepam (Dalmane), quazepam (Doral), triazolam
(Halcion), estazolam (ProSom), and temazepam
(Restoril), for insomnia. Benzodiazepine drugs are
described in the essay on antianxiety drugs. Zaleplon
(Sonata) is another anti-insomnia drug that is not
related to other drugs with the same effect. The barbiturates, such as pentobarbital (Nembutal) and secobarbital (Seconal) are no longer commonly used to treat
insomnia because they are too dangerous if they are
taken in overdoses. For patients with mild insomnia,
some antihistamines, such as diphenhydramine
(Benadryl) or hydroxyzine (Atarax) may be used,
since these also cause sleepiness.
Zolpidem is available only with a physician’s
prescription and comes in tablet form.
317

Anti-insomnia drugs

acid forms crystals, which then cause the aforementioned symptoms. Although uric acid levels must be
high in order for patients to have crystals form, and
therefore have gout, most persons with high uric acid
levels don’t ever have symptoms. Thus, recent criteria
for use of anti-hyperuricemic agents suggest that
patients who have never experienced symptoms of
gout should not receive drug therapy, unless their
hyperuricemia is associated with cancer (may lead to
kidney damage) or certain rare genetic disorders
(McGill, Rheumatologist, University of Sydney,
Australia, 2000).

Anti-insomnia drugs

Precautions
Anti-Insomnia Drugs

Brand Name (Generic
Name)

Possible Common Side Effects Include:

Ambien (zolpidem tartrate)
Dalmane (flurazepam
hydrochloride)
Doral (quazepam)

Daytime drowsiness, dizziness, headache
Decreased coordination, lightheadedness,
dizziness
Daytime drowsiness, headache, dry mouth,
fatigue
Decreased coordination, chest pain, memory impairment
Dizziness, headache, nausea, weakness
Dizziness, fatigue, nausea, headache,
sluggishness

Halcion (triazolam)
ProSom (estazolam)
Restoril (temazepam)

KEY TERMS
Asthma—A disease in which the air passages of the
lungs become inflamed and narrowed.
Bronchitis—Inflammation of the air passages of the
lungs.
Emphysema—A lung disease in which breathing
becomes difficult.
Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Sleep apnea—A condition in which a person temporarily stops breathing during sleep.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug to which he or she has
become dependent.

Recommended dosage
The recommended dose for adults is 5-10 mg just
before bedtime. The medicine works quickly, often
within 20 minutes, so it should be taken right before
going to bed.
For older people and others who may be more
sensitive to the drug’s effects, the recommended starting dosage is 5 mg just before bedtime.
Zolpidem may be taken with food or on an
empty stomach, but it may work faster when taken
on an empty stomach. Check with a physician or
pharmacists for instructions on how to take the
medicine.
318

Zolpidem is meant only for short-term treatment
of insomnia. If sleep problems last more than seven to
10 days, check with a physician. Longer-lasting sleep
problems could be a sign of another medical problem.
Also, this drug may lose its effectiveness when taken
every night for more than a few weeks.
Some people feel drowsy, dizzy, confused, lightheaded, or less alert the morning after they have taken
zolpidem. The medicine may also cause clumsiness,
unsteadiness, double vision, or other vision problems
the next day. For these reasons, anyone who takes
these drugs should not drive, use machines or do anything else that might be dangerous until they have
found out how zolpidem affects them.
This medicine has caused cause behavior changes
in some people, similar to those seen in people whose
behavior changes when they drink alcohol. Examples
include giddiness and rage. More extreme changes,
such as confusion, agitation, and hallucinations, also
are possible. Anyone who starts having strange or
unusual thoughts or behavior while taking this medicine should get in touch with his or her physician.
Zolpidem and other sleep medicines may cause a
special type of temporary memory loss, in which the
person does not remember what happens between the
time they take the medicine and the time its effects
wear off. This is usually not a problem, because people
go to sleep right after taking the medicine and stay
asleep until its effects wear off. But it could be a
problem for anyone who has to wake up before getting
a full night’s sleep (seven to eight hours). In particular,
travelers should not take this medicine on airplane
flights of less than seven to eight hours.
Because zolpidem works work on the central
nervous system, it may add to the effects of alcohol
and other drugs that slow down the central nervous
system, such as antihistamines, cold medicine,
allergy medicine, medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants.
Zolpidem may also add to the effects of anesthetics,
including those used for dental procedures. The
combined effects of zolpidem and alcohol or other
CNS depressants (drugs that slow the central nervous system) can be very dangerous, leading to
unconsciousness or even death. People who take
zolpidem should not drink alcohol and should
check with their physicians before taking any other
CNS depressant. Anyone who shows signs of an
overdose or of the effects of combining zolpidem
drugs with alcohol or other drugs should have
immediate emergency help. Warning signs include
GALE ENCYCLOPEDIA OF MEDICINE

Anyone who takes zolpidem for more than 1–2
weeks should not stop taking it without first checking
with a physician. Stopping the drug abruptly may
cause rebound insomnia; increased difficulty falling
asleep for the first one of two nights after the drug
has been discontinued. In rare cases, withdrawal
symptoms, such as vomiting, cramps, and unpleasant
feelings may occur. Gradual tapering may be
necessary.
Older people may be more sensitive to the effects
of zolpidem. This may increase the chance of side
effects, such as confusion, and may also increase the
risk of falling.
In people with breathing problems, zolpidem may
worsen the symptoms.
Special conditions
People with certain other medical conditions or
who are taking certain other medicines can have problems if they take zolpidem. Before taking this medicine, be sure to let the physician know about any of
these conditions:
ALLERGIES. Anyone who has had unusual reactions to zolpidem in the past should let his or her
physician know before taking the drugs again. The
physician should also be told about any allergies to
foods, dyes, preservatives, or other substances.
PREGNANCY. Women who are pregnant or who

may become pregnant should check with their physicians about the safety of using zolpidem during
pregnancy.

USE OF CERTAIN MEDICINES. Taking zolpidem with
certain other drugs may affect the way the drugs work
or may increase the chance of side effects.

Side effects
The most common minor side effects are daytime
drowsiness or a ‘‘drugged’’ feeling, vision problems,
memory problems, nightmares or unusual dreams,
vomiting, nausea, abdominal or stomach pain, diarrhea, dry mouth, headache, and general feeling of discomfort or illness. These problems usually go away as
the body adjusts to the drug and do not require medical treatment.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with the physician who prescribed the medicine
as soon as possible:


Confusion



Depression



Clumsiness or unsteadiness

Patients who take zolpidem may notice side
effects for several weeks after they stop taking the
drug. They should check with their physicians if
these or other troublesome symptoms occur:


Agitation, nervousness, feelings of panic



Uncontrolled crying



Worsening of mental or emotional problems



Seizures



Tremors



Lightheadedness



Sweating



Flushing



Nausea or abdominal or stomach cramps



Muscle cramps



Unusual tiredness or weakness

BREASTFEEDING. Women who are breastfeeding

should check with their physicians before using
zolpidem.
OTHER MEDICAL CONDITIONS. Before using zolpidem, people with any of these medical problems
should make sure their physicians are aware of their
conditions:


Chronic lung diseases (emphysema, asthma, or
chronic bronchitis)



Liver disease



Kidney disease



Current or past alcohol or drug abuse



Depression



Sleep apnea

GALE ENCYCLOPEDIA OF MEDICINE

Other rare side effects may occur. Anyone who
has unusual symptoms after taking zolpidem should
get in touch with his or her physician.

Interactions
Zolpidem may interact with other medicines.
When this happens, the effects of one or both of the
drugs may change or the risk of side effects may be
greater. Anyone who takes zolpidem should let the
physician know all other medicines he or she is
319

Anti-insomnia drugs

severe drowsiness, severe nausea or vomiting, breathing problems, and staggering.

Anti-itch drugs

taking. Among the drugs that may interact with zolpidem are:


Other central nervous system (CNS) depressants
such as medicine for allergies, colds, hay fever, and
asthma; sedatives; tranquilizers; prescription pain
medicine; muscle relaxants; medicine for seizures;
barbiturates; and anesthetics.



The major tranquilizer chlorpromazine (Thorazine).



Tricyclic antidepressants such as
(Tofranil) and amitriptyline (Elavil).

Anesthesia—Treatment with medicine that causes
a loss of feeling, especially pain. Local anesthesia
numbs only part of the body; general anesthesia
causes loss of consciousness.
Antihistamine—Medicine that prevents or relieves
allergy symptoms.

imipramine

Nancy Ross-Flanigan

I Anti-itch drugs
Definition
Anti-itch drugs are medicines taken by mouth or
by injection to relieve itching.

Purpose
The medicine described here, hydroxyzine, is a
type of antihistamine used to relieve itching caused
by allergic reactions. An allergic reaction occurs
when the body is unusually sensitive to some substance, such as pollen, dust, mold, or certain foods or
medicine. The body reacts by releasing a chemical
called histamine that causes itching and other symptoms, such as sneezing and watery eyes. Antihistamines
reduce the symptoms by blocking the effects of
histamine.
Hydroxyzine is also prescribed for anxiety and to
help people relax before or after having general
anesthesia.

Description
Anti-itch drugs, also called antipruritic drugs, are
available only with a physician’s prescription and
come in tablet and injectable forms. Some commonly
used brands of the anti-itch drug hydroxyzine are
Atarax and Vistaril.

Recommended dosage
When prescribed for itching, the usual dosage for
adults is 25 mg, three to four times a day. For children
over six years of age, the usual dosage 50-100 mg per
320

KEY TERMS

day, divided into several small doses. The usual dosage
for children under six years of age is 50 mg per day,
divided into several small doses.
The dosage may be different for different people.
Check with the physician who prescribed the drug
or the pharmacist who filled the prescription for the
correct dosage, and take the medicine exactly as
directed.

Precautions
This medicine should not be used for more than
four months at a time because its effects can wear off.
See a physician regularly while taking the medicine to
determine whether it is still needed.
Hydroxyzine may add to the effects of alcohol and
other drugs that slow down the central nervous system, such as other antihistamines, cold medicine,
allergy medicine, sleep aids, medicine for seizures,
tranquilizers, some pain relievers, and muscle relaxants. Anyone taking hydroxyzine should not drink
alcohol and should check with his or her physician
before taking any of the above.
Some people feel drowsy or less alert when using
this medicine. Anyone who takes it should not drive,
use machines, or do anything else that might be
dangerous until they have found out how the drugs
affect them.
Anyone who has had unusual reactions to hydroxyzine in the past should let his or her physician know
before taking the medicine again. The physician
should also be told about any allergies to foods,
dyes, preservatives, or other substances.
A woman who is pregnant or who may become
pregnant should check with her physician before taking this medicine. In studies of laboratory animals,
hydroxyzine has caused birth defects when taken during pregnancy. Although the drug’s effects on pregnant women have not been fully studied, physicians
advise against taking it in early pregnancy.
GALE ENCYCLOPEDIA OF MEDICINE

Side effects

KEY TERMS
Glucose—A simple sugar that serves as the body’s
main source of energy.
Hypoglycemia—Abnormally low levels of glucose
in the blood.

The most common side effect, drowsiness, usually
goes away as the body adjusts to the drug. If it does
not, reducing the dosage may be necessary. Other side
effects, such as dry mouth, also may occur and do not
need medical attention unless they continue.

Organism—An individual of some type of life form,
such as a plant or an animal.
Parasite—An organism that lives and feeds in or on
another organism (the host) and does nothing to
benefit the host.

More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with the physician who prescribed the medicine
as soon as possible:

Protozoa—Animal-like, one-celled organisms,
some of which cause diseases in people.



Twitches or tremors



Convulsions (seizures).

Purpura—A spotty or patchy purplish rash caused
by bleeding under the surface of the skin.

Interactions

Psoriasis—A skin disease in which people have
itchy, scaly, red patches on the skin.

Purpose

Hydroxyzine may interact with other medicines.
When this happens, the effects of one or both of the
drugs may change or the risk of side effects may be
greater. Anyone who takes hydroxyzine should let the
physician know all other medicines he or she is taking.
Among the drugs that may interact with hydroxyzine are:


Barbiturates such as phenobarbital and secobarbital
(Seconal)



Opioid (narcotic) pain medicines such as meperidine
(Demerol) and oxycodone (Percocet)



Non-narcotic pain medicines such as acetaminophen
(Tylenol) and ibuprofen (Motrin, Advil).

The list above may not include every drug that
interacts with hydroxyzine. Be sure to check with a
physician or pharmacist before combining hydroxyzine with any other prescription or nonprescription
(over-the-counter) medicine.
Nancy Ross-Flanigan

I Antimalarial drugs
Definition
Antimalarial drugs are medicines that prevent or
treat malaria.
GALE ENCYCLOPEDIA OF MEDICINE

Antimalarial drugs treat or prevent malaria, a
disease that occurs in tropical, subtropical, and
some temperate regions of the world. The disease
is caused by a parasite, Plasmodium, which belongs
to a group of one-celled organisms known as protozoa. The only way to get malaria is to be bitten by a
certain type of mosquito that has bitten someone
who has the disease. Thanks to mosquito control
programs, malaria has been eliminated in the
United States, almost all of Europe, and large
parts of Central and South America. However, mosquito control has not worked well in other parts
of the world, and malaria continues to be a
major health problem in parts of Africa, Southeast
Asia, Latin America, Haiti, the Dominican Republic,
and some Pacific Islands. Every year, some
30,000 Americans and Europeans who travel to
these areas get malaria. People planning to travel to
the tropics are often advised to take antimalarial
drugs before, during, and after their trips, to help
them avoid getting the disease and bringing it home
with them. These drugs kill Plasmodium or prevent
its growth.
In recent years, some strains of Plasmodium
have become resistant to antimalarial drugs, and
medical researchers have stepped up efforts to
develop a malaria vaccine. In early 1997, researchers reported encouraging results from a small study
of one vaccine and planned to test the vaccine
in Africa.
321

Antimalarial drugs

BREASTFEEDING. Women who are breastfeeding
should also check with their physicians before using
hydroxyzine. The medicine may pass into breast milk
and may cause problems in nursing babies whose
mothers take it.

Antimalarial drugs

Description
Antimalarial drugs are available only with a physician’s prescription. They come in tablet, capsule, and
injectable forms. Among the commonly used antimalarial drugs are chloroquine (Aralen), mefloquine
(Lariam), primaquine, pyrimethamine (Daraprim),
and quinine. Other drugs are constantly in development. In early 2004, scientists were researching promising new agents called beat-amino hydroxamates
and amino acid-conjugated quinolinamines.

Recommended dosage
Recommended dosage depends on the type of
antimalarial drug, its strength, and the form in which
it is being used (such as tablet or injection). The dosage
may also be different for different people. The physician who prescribed the drug or the pharmacist who
filled the prescription can recommend the correct
dosage. This medicine should be taken exactly as
directed and for the full time of treatment. If the
drug is being taken to treat malaria, it should not be
stopped just because symptoms begin to improve.
Symptoms may return if the drug is stopped too
soon. Larger or more frequent doses than the physician has ordered should never be taken, nor should the
drug be taken for longer than directed.
Travelers taking this medicine to prevent malaria
may be told to take it for one to two weeks before their
trip and for four weeks afterward, as well as for the
whole time they are away. It is important to follow
these directions.
Antimalarial drugs work best when they are taken
on a regular schedule. When taken once a week to
prevent malaria, they should be taken on the same day
every week. When taken daily or several times a day to
treat malaria, they should be taken at the same time
every day. Doses should not be missed or skipped.
Some antimalarial drugs should be taken with
meals or with milk to prevent upset stomach. Others
must be taken with a full glass of water. It is important
to follow directions along with the prescription.

Precautions
Antimalarial drugs may cause lightheadedness,
dizziness, blurred vision and other vision changes.
Anyone who takes these drugs should not drive, use
machines or do anything else that might be dangerous
until they have found out how the drugs affect them.
The antimalarial drug mefloquine (Lariam) has
received attention because of reports that it causes
panic attacks, hallucinations, anxiety, depression,
322

paranoia, and other mental and mood changes, sometimes lasting for months after the last dose. In fact, the
U.S. Food and Drug Administration (FDA) began
requiring warnings with Lariam beginning in July
2003 because of serious psychiatric effects caused by
the drug. Pharmacists are required to include a 2,000word medication guide detailing the warnings.
Anyone who has unexplained anxiety, depression,
restlessness, confusion, or other troubling mental or
mood changes after taking mefloquine should call a
physician right away. Switching to a different antimalarial drug may be an alternative and can allow the side
effects to stop.
Anyone taking antimalarial drugs to prevent
malaria who develops a fever or flu-like symptoms
while taking the medicine or within 2-3 months after
traveling to an area where malaria is common should
call a physician immediately.
If the medicine is being taken to treat malaria, and
symptoms stay the same or get worse, The patient
should check with the physician who prescribed the
medicine.
Patients who take this medicine over a long period
of time need to have a physician check them periodically for unwanted side effects.
Babies and children are especially sensitive to the
antimalarial drug chloroquine. Not only are they more
likely to have side effects from the medicine, but they
are also at greater risk of being harmed by an overdose. A single 300-mg tablet could kill a small child.
This medicine should be kept out of the reach of children
and safety vials should be used.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take antimalarial drugs. Before taking these
drugs, the physician should know about any of these
conditions:
ALLERGIES. Anyone who has had unusual reactions to antimalarial drugs or related medicines in
the past should let his or her physician know before
taking the drugs again. The physician should also be
told about any allergies to foods, dyes, preservatives,
or other substances.
PREGNANCY. In laboratory animal studies, some
antimalarial drugs cause birth defects. But it is also
risky for a pregnant woman to get malaria. Untreated
malaria can cause premature birth, stillbirth, and
miscarriage. When given in low doses to prevent
malaria, antimalarial drugs have not been reported

GALE ENCYCLOPEDIA OF MEDICINE

BREASTFEEDING. Some antimalarial drugs pass
into breast milk. Although no problems have been
reported in nursing babies whose mothers took antimalarial drugs, babies and young children are particularly sensitive to some of these drugs. Women who are
breastfeeding should check with their physicians
before using antimalarial drugs.
OTHER MEDICAL CONDITIONS. Before using antimalarial drugs, people who have any of these medical problems (or have had them in the past) should
make sure their physicians are aware of their
conditions:

Side effects
High doses of the antimalarial drug pyrimethamine may cause blood problems that can interfere with
healing and increase the risk of infection. People taking this drug should be careful not to injure their gums
when brushing or flossing their teeth or using toothpicks. If possible, dental work should be postponed
until treatment is complete and the blood has returned
to normal.
The most common side effects of antimalarial
drugs are diarrhea, nausea or vomiting, stomach
cramps or pain, loss of appetite, headache, itching,
difficulty concentrating, dizziness, lightheadedness,
and sleep problems. These problems usually go away
as the body adjusts to the drug and do not require
medical treatment. Less common side effects, such as
hair loss or loss of color in the hair; skin rash; or blueblack discoloration of the skin, fingernails, or inside of
the mouth also may occur and do not need medical
attention unless they are long-lasting.



Blood disease



Liver disease



Nerve or brain disease or disorder, including seizures
(convulsions)



Past or current mental disorder



Stomach or intestinal disease



Blurred vision or any other vision changes



Deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD), which is important in the breakdown of sugar in the body



Convulsions (seizures)



Mood or mental changes



Hallucinations



Anxiety



Deficiency of the enzyme nicotinamide adenine dinucleotide (NADH) methemoglobin reductase

More serious side effects are not common, but
may occur. If any of the following side effects occur,
the physician who prescribed the medicine should be
contacted immediately:



Psoriasis



Confusion



Heart disease



Weakness or unusual tiredness



Family or personal history of the genetic condition
favism (a hereditary allergic condition)



Unusual bruising or bleeding



Hearing loss or ringing or buzzing in the ears



Fever, with or without sore throat



Slow heartbeat



Pain in the back or legs



Dark urine



Pale skin



Taste changes



Soreness, swelling, or burning sensation in the
tongue.



Family or personal history of hemolytic anemia, a
condition in which red blood cells are destroyed



Purpura



Hypoglycemia (low blood sugar)



Blackwater fever (a serious complication of one type
of malaria)



Myasthenia gravis (a disease of the nerves and
muscles).

USE OF CERTAIN MEDICINES. Taking antimalarial
drugs with certain other drugs may affect the way
the drugs work or may increase the chance of side
effects.

GALE ENCYCLOPEDIA OF MEDICINE

Other rare side effects may occur. Anyone who
has unusual symptoms after taking anantimalarial
drug should get in touch with his or her physician.
323

Antimalarial drugs

to cause birth defects in humans. If possible, pregnant
women should avoid traveling to areas where they
could get malaria. If travel is necessary, women who
are pregnant or who may become pregnant should
check with their physicians about the use of antimalarial drugs.

Antimigraine drugs

Interactions
Some antimalarial drugs may interact with other
medicines. When this happens, the effects of one or
both of the drugs may change or the risk of side effects
may be greater. Anyone who takes antimalarial drugs
should let the physician know all other medicines he or
she is taking. Among the drugs that interact with some
antimalarial drugs are:


Beta blockers such as atenolol (Tenormin), propranolol (Inderal), and metoprolol (Lopressor)



Calcium channel blockers such as diltiazem
(Cardizem), nicardipene (Cardene), and nifedipine
(Procardia)



Other antimalarial drugs



Quinidine, used to treat abnormal heart rhythms



Antiseizure medicines such as vaproic acid derivatives (Depakote or Depakene)



Oral typhoid vaccine



Diabetes medicines taken by mouth



Sulfonamides (sulfa drugs)



Vitamin K



Anticancer drugs



Medicine for overactive thyroid



Antiviral drugs such as zidovudine (Retrovir).

The list above does not include every medicine
that may interact with every antimalarial drug. It is
advised to check with a physician or pharmacist before
combining an antimalarial drug with any other
prescription or nonprescription (over-the-counter)
medicine.
Resources
PERIODICALS

‘‘Amino Acid-conjugated Quinolinamines Are Potent
Antimalarials.’’ Drug Week (March 12, 2004): 142.
‘‘FDA Requires Warnings on Anti-malaria Drug Lariam.’’
Consumer Reports (January 2004): 45.
‘‘Glycosylated Beta-amino Hydroxamates Show Promise as
Antimalarials.’’ Malaria Weekly (February 2, 2004): 2.
OTHER

‘‘Should You Take Lariam?’’ Travel Health Information
Page. <http://travelhealth.com/lariam.htm>.

Nancy Ross-Flanigan
Teresa G. Odle

Antimicrobial agents see Antibiotics
324

I Antimigraine drugs
Definition
Antimigraine drugs are medicines used to prevent
or reduce the severity of migraine headaches.

Purpose
Migraine headaches usually cause a throbbing
pain on one side of the head. Nausea, vomiting, dizziness, increased sensitivity to light and sound, and
other symptoms may accompany the pain. The attacks
may last for several hours or for a day or more and
may come as often as several times a week. Some
people who get migraine headaches have warning signals before the headaches begin, such as restlessness,
tingling in an arm or leg, or seeing patterns of flashing
lights. This set of signals is called an aura. The antimigraine drugs discussed in this section are meant to
be taken as soon as the pain begins, to relieve the pain
and other symptoms. Other types of drugs, such as
antiseizure medicines, antidepressants, calcium channel blockers and beta blockers, are sometimes prescribed to prevent attacks in people with very severe
or frequent migraines.

Description
Migraine is thought to be caused by electrical and
chemical imbalances in certain parts of the brain.
These imbalances affect the blood vessels in the
brain – first tightening them up, then widening them.
As the blood vessels widen, they stimulate the release
of chemicals that increase sensitivity to pain and cause
inflammation and swelling. Antimigraine drugs are
believed to work by correcting the imbalances and by
tightening the blood vessels.
Examples of drugs in this group are ergotamine
(Cafergot), naratriptan (Amerge), sumatriptan
(Imitrex), rizatriptan (Maxalt), almotriptan (Axert),
and zolmitriptan (Zomig). Methysergide maleate
(Sansert) may be used by patients whose headaches
are not controlled by other drugs, while some patients
do well on other drugs. For example, combinations
or ergotamine and caffeine may be very effective.
The caffeine acts by constricting blood vessels to
relieve the headache. Sometimes, an analgesic such
as acetaminophen, caffeine, and a barbiturate which
acts as a sedative, are combined, as in Fioricet and
similar compounds. These medicines are available
only with a physician’s prescription and come in
several forms. Ergotamine is available as tablets
GALE ENCYCLOPEDIA OF MEDICINE

Brand Name
(Generic Name)
Cafergot

Imitrex (sumatriptan
succinate)
Inderal (propranolol
hydrochloride)
Midrin

Take at the first sign of a migraine attack. Patients
who get warning signals (aura) may take the drug as
soon as they know a headache is coming.
Possible Common Side Effects Include:
Nausea, increased blood pressure, fluid
retention, numbness, increased heart rate,
tingling sensation
Burning, flushing, neck pain, inflammation at
injection site, sore throat, tingling sensation
Constipation or diarrhea, headache, nausea, rash

TABLETS. No more than 6 tablets for any single

attack.
No more than 10 tablets per week.
SUPPOSITORIES. No more than 2 suppositories for

any single attack.
Dizziness, rash

No more than 5 suppositories per week.
Naratriptan

KEY TERMS
Anticonvulsant—A type of drug given to prevent
seizures. Some patients with migraines can be
treated effectively with an anticonvulsant.
Aura—A set of warning symptoms, such as seeing
flashing lights, that some people have 10–30
minutes before a migraine attack.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Status migrainosus—The medical term for an acute
migraine headache that lasts 72 hours or longer.

Take as soon as pain or other migraine symptoms
begin. Also effective if taken any time during an
attack. Do not take the drug until the pain actually
starts as not all auras result in a migraine.
TABLETS. Usual dose is one 1-mg tablet taken with
water or other liquid.

Doses of 2.5-mg may be used, but they may cause
more side effects.
If the headache returns or if there is only partial
response, the dose may be repeated once after 4 hours,
for a maximum dose of 5 mg in a 24-hour period.
Larger doses do not seem to offer any benefit.
Sumatriptan

and rectal suppositories; sumatriptan as tablets,
injections, and nasal spray; and zolmitriptan as
tablets.

Take as soon as pain or other migraine symptoms
begin. Also effective if taken any time during an
attack. Do not take the drug until the pain actually
starts as not all auras result in a migraine.

Antimigraine drugs are used to treat headaches
once they have started. These drugs should not be
taken to prevent headaches.

TABLETS. Usual dose is one 25-mg tablet, taken
with water or other liquid.

Some patients are given anti-epileptic drugs,
which are also known as anticonvulsants, to treat
migraine headaches. As of 2003, sodium valproate
(Epilim) is the only anticonvulsant approved by the
Food and Drug Administration (FDA) for prevention of migraine. Such newer anticonvulsants as
gabapentin (Neurontin) and topiramate (Topamax)
are being evaluated as migraine preventives as of
early 2004.

Recommended dosage
Recommended dosage depends on the type of
drug. Typical recommended dosages for adults are
given below for each type of drug.
GALE ENCYCLOPEDIA OF MEDICINE

Doses should be spaced at least 2 hours apart.
Anyone with liver disease should consult with a
physician for proper dosing.
INJECTIONS. No more than 6 mg per dose, injected

under the skin.
No more than two 6-mg injections per day. These
doses should be taken at least 1 hour apart.
Zolmitriptan
Take as soon as symptoms begin.
TABLETS. Usual dose is 1–5 mg. Additional doses
may be taken at 2-hour intervals.

No more than 10 mg per 24 hour period.
325

Antimigraine drugs

Ergotamine
Antimigraine Drugs

Antimigraine drugs

General dosage advice
Always take antimigraine drugs exactly as directed. Never take larger or more frequent doses, and do
not take the drug for longer than directed.
If possible, lie down and relax in a dark, quiet
room for a few hours after taking the medicine.

Precautions
These drugs should be used only to treat the type
of headache for which they were prescribed. Patients
should not use them for other headaches, such as those
caused by stress or too much alcohol, unless directed
to do so by a physician.
Anyone whose headache is unlike any previous
headache should check with a physician before taking
these drugs. If the headache is far worse than any
other, emergency medical treatment should be sought
immediately.
Taking too much of the antimigraine drug ergotamine (Cafergot), can lead to ergot poisoning. Symptoms
include headache, muscle pain, numbness, coldness, and
unusually pale fingers and toes. If not treated, the condition can lead to gangrene (tissue death).
Sumatriptan (Imitrex), naratriptan (Amerge),
rizatriptan (Maxalt) and zolmitriptan (Zomig) may
interact with ergotamine. These drugs should not be
taken within 24 hours of taking any drug containing
ergotamine.
Some antimigraine drugs work by tightening
blood vessels in the brain. Because these drugs also
affect blood vessels in other parts of the body, people
with coronary heart disease, circulatory problems, or
high blood pressure should not take these medicines
unless directed to do so by their physicians.
About 40% of all migraine attacks do not
respond to treatment with triptans or any other
medication. If the headache lasts longer than 72
hours—a condition known as status migrainosus—
the patient may be given narcotic medications to
bring on sleep and stop the attack. Patients with
status migrainosus are often hospitalized because
they are likely to be dehydrated from severe nausea
and vomiting.
Special conditions
People with certain other medical conditions or
who are taking certain other medicines can have problems if they take antimigraine drugs. Before taking
these drugs, be sure to let the physician know about
any of these conditions:
326

ALLERGIES. Anyone who has had unusual reactions to ergotamine, caffeine, sumatriptan, zolmitriptan, or other antimigraine drugs in the past should let
his or her physician know before taking the drugs
again. The physician should also be told about any
allergies to foods, dyes, preservatives, or other
substances.
PREGNANCY. Women who are pregnant should
not take ergotamine (Cafergot). The effects of other
antimigraine drugs during pregnancy have not been
well studied. Any woman who is pregnant or plans to
become pregnant should let her physician know before
an antimigraine drug is prescribed.
BREASTFEEDING. Some antimigraine drugs can
pass into breast milk and may cause serious problems
in nursing babies. Women who are breastfeeding
should check with their physicians about whether to
stop breastfeeding while taking the medicine.
OTHER MEDICAL CONDITIONS. Before using antimigraine drugs, people with any of these medical problems should make sure their physicians know about
their conditions:


Coronary heart disease



Angina (crushing chest pain)



Circulatory problems or blood vessel disease



High blood pressure



Liver problems



Kidney problems



Any infection



Eye problems.

USE OF CERTAIN MEDICINES. Taking antimigraine
drugs certain other drugs may affect the way the drugs
work or may increase the chance of side effects.

Side effects
The most common side effects are fluid retention, flushing; high blood pressure; unusually fast
or slow heart rate; numbness; tingling; itching;
nausea; vomiting; weakness; neck or jaw pain and
stiffness; feelings of tightness, heaviness, warmth,
or coldness; sore throat; and discomfort of the
mouth and tongue.
More serious side effects are not common, but
they may occur. If any of the following side effects
occur, call a physician immediately:


Tightness in the chest



Bluish tinge to the skin



Cold arms and legs
GALE ENCYCLOPEDIA OF MEDICINE

Signs of gangrene, such as coldness, dryness, and a
shriveled or black appearance of a body part



Monoamine oxidase inhibitors such as phenelzine
(Nardil) and tranylcypromine (Parnate)



Dizziness





Drowsiness

Certain antidepressants, such as sertraline (Zoloft),
fluoxetine (Prozac), and paroxetine (Paxil)

Shortness of breath or wheezing





Fluvoxamine (Luvox), prescribed for obsessive compulsive disorder or chronic pain.



Skin rash



Swelling of the eyelids or face.

Anticonvulsants should not be taken together
with aspirin, alcohol, or tranquilizers.

Possible side effects with anticonvulsants include
dizziness, drowsiness, emotional upset, skin rash, temporary hair loss, nausea, and irregular menstrual
periods.

Remember naratriptan, sumatriptan, rizatriptan
and zolmitriptan may interact with ergotamine. These
drugs should not be taken within 24 hours of taking
any drug containing ergotamine.

Other side effects may occur with any antimigraine drug. Anyone who has unusual symptoms
after taking this medicine should get in touch with
his or her physician.

Resources

Alternative treatments
There are two herbal remedies that are reported to
be effective as alternative treatments for migraine. One
is feverfew (Tanacetum parthenium), an herb related to
the daisy that is traditionally used in England to prevent migraines. Published studies indicate that feverfew can reduce the frequency and intensity of
migraines. It does not, however, relieve pain once the
headache has begun. The other herbal remedy is butterbur root (Petasites hybridus). Petadolex is a natural
preparation made from butterbur root that has been
sold in Germany since the 1970s as a migraine preventive. Petadolex has been available in the United States
since December 1998.

Interactions
Antimigraine drugs may interact with other medicines. When this happens, the effects of one or both of
the drugs may change, or the risk of side effects may be
greater. Anyone who takes these drugs should let the
physician know all other medicines he or she is taking.
Among the drugs that may interact with antimigraine
drugs are:


Beta blockers such as atenolol (Tenormin) and propranolol (Inderal)



Drugs that tighten blood vessels such as epinephrine
(EpiPen) and pseudoephedrine (Sudafed)



Nicotine such as cigarettes or Nicoderm, Habitrol,
and other smoking-cessation drugs



Certain antibiotics, such as erythromycin and clarithromycin (Biaxin)

GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

American Psychiatric Association.Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, DC: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Headache.’’ Section 14, Chapter 168 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2002.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychogenic Pain Syndromes.’’ Section 14, Chapter
167 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II. ‘‘CAM Therapies for Specific Conditions:
Headache.’’ New York: Simon & Schuster, 2002.
PERIODICALS

Ceballos Hernansanz, M. A., R. Sanchez Roy, A. Cano
Orgaz, et al. ‘‘Migraine Treatment Patterns and Patient
Satisfaction with Prior Therapy: A Substudy of a
Multicenter Trial of Rizatriptan Effectiveness.’’
Clinical Therapeutics 25 (July 2003): 2053–2069.
Corbo, J. ‘‘The Role of Anticonvulsants in Preventive
Migraine Therapy.’’ Current Pain and Headache
Reports 7 (February 2003): 63–66.
Dodick, D. W. ‘‘A Review of the Clinical Efficacy and
Tolerability of Almotriptan in Acute Migraine.’’ Expert
Opinion in Pharmacotherapy 4 (July 2003): 1157–1163.
Dowson, A. J., and B. R. Charlesworth. ‘‘Patients with
Migraine Prefer Zolmitriptan Orally Disintegrating
Tablet to Sumatriptan Conventional Oral Tablet.’’
International Journal of Clinical Practice 57 (September
2003): 573–576.
Johannessen, C. U., and S. I. Johannessen. ‘‘Valproate: Past,
Present, and Future.’’ CNS Drug Review 9 (Summer
2003): 199–216.
Sahai, Soma, MD, Robert Cowan, MD, and David Y. Ko,
MD. ‘‘Pathophysiology and Treatment of Migraine
and Related Headache.’’ eMedicine April 30, 2002.
327

Antimigraine drugs



Antimyocardial antibody test

Tepper, S. J., and D. Millson. ‘‘Safety Profile of the
Triptans.’’ Expert Opinion on Drug Safety 2 (March
2003): 123–132.

Nancy Ross-Flanigan
Rebecca J. Frey, PhD

I Antimyocardial antibody test
Definition
Testing for antimyocardial antibodies is done
when evaluating a person for heart damage or heart
disease.

Purpose
Antimyocardial antibodies are autoantibodies.
Normal antibodies are special proteins built by the
body as a defense against foreign material entering the
body. Autoantibodies are also proteins built by the body,
but instead of attacking foreign material, they inappropriately attack the body’s own cells. Antimyocardial antibodies attack a person’s heart muscle, or myocardium.
This test may be done on a person who recently
had trauma to the heart, such as heart surgery or a
myocardial infarction (heart attack). It also may be
done on someone with heart disease, such as cardiomyopathy or rheumatic fever.
Although the presence of antimyocardial antibodies does not diagnose heart damage or disease, there is
a connection between the presence of these antibodies
and damage to the heart. The amount of damage, however, cannot be predicted by the amount of antibodies.
These antibodies usually appear after heart surgery
or the beginning of disease, but they may be present before
surgery or the onset of disease. In 30% of people with
myocardial infarction and 70% of people having heart
surgery, antimyocardial antibodies will appear within
two to three weeks and stay for three to eight weeks.

Description
A 5-10 mL sample of venous blood is drawn from
the patient’s arm in the region of the inner elbow.
Antimyocardial antibodies are detected by combining
a patient’s serum (clear, thin, sticky fluid in blood)
with cells from animal heart tissue, usually that of a
monkey. Antimyocardial antibodies in the serum bind
to the heart tissue cells. A fluorescent dye is then added
328

KEY TERMS
Antibody—A special protein built by the body as
a defense against foreign material entering the
body.
Antimyocardial antibody—An autoantibody that
attacks a person’s own heart muscle, or
myocardium.
Autoantibody— An antibody that attacks the
body’s own cells or tissues.
Myocardial infarction—A block in the blood supply to the heart, resulting in what is commonly
called a heart attack.
Myocardium—The muscular middle layer of the
heart.
Titer—A dilution of a substance with an exact
known amount of fluid. For example, one part of
serum diluted with four parts of saline is a titer
of 1:4.

to the mixture. This dye will attach to any antibodies
and heart tissue cells bound together. The final mixture is studied under a microscope that is designed to
show fluorescence. If fluorescent cells are seen under
the microscope, the test is positive.
When the test is positive, the next step is to find
out how much antibody is present. The patient’s
serum is diluted, or titered, and the test is done
again. The serum is then further diluted and the test
repeated until the serum is so dilute that fluorescence is
no longer seen. The last dilution that showed fluorescence is the titer reported.

Preparation
No fasting or special prepartion is needed. Before
the test is done it should be explained to the patient.

Aftercare
Discomfort or bruising may occur at the puncture
site after the blood is drawn or the person may feel
dizzy or faint. Pressure to the puncture site until the
bleeding stops reduces bruising. Warm packs on the
puncture site relieve discomfort.

Normal results
Antimyocardial antibodies are not normally seen
in healthy individuals.
GALE ENCYCLOPEDIA OF MEDICINE

Antinausea Drugs

A positive result means that antimyocardial antibodies are present and that heart disease or damage is likely.
Further testing may be needed as other autoantibodies
could also be present, causing a false abnormal test.

Brand Name (Generic
Name)
Compazine
(phochlorperazine)
Phenergan (promethazine hydrochloride)
Reglan (metoclopramide
hydrochloride)
Tigan (trimethobenzamide hydrochloride)
Zofan (ondansetron
hydrochloride)

Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Nancy J. Nordenson

I Antinausea drugs

Central nervous system—The brain and spinal cord.
Spasm—Sudden, involuntary tensing of a muscle or
a group of muscles.

Purpose
Antinausea drugs such as prochlorperazine
(Compazine), usually control both nausea and vomiting. Prochlorperazine is also sometimes prescribed for
symptoms of mental disorders, such as schizophrenia.

Prochlorperazine is available only with a physician’s prescription. It is sold in syrup, capsule, tablet,
injection, and suppository forms.

Recommended dosage
To control nausea and vomiting in adults, the
usual dose is:


Tablets—one 5-mg or 10-mg tablet three to four
times a day



Extended-release capsules—one 15-mg capsule first
thing in the morning or one 10-mg capsule every
12 hours



Suppository—25 mg, twice a day

GALE ENCYCLOPEDIA OF MEDICINE

Constipation, headache, fatigue, abdominal
pain

Anesthetic—Medicine that causes a loss of feeling,
especially pain. Some anesthetics also cause a loss
of consciousness.
Antihistamine—Medicine that prevents or relieves
allergy symptoms.

Antinausea drugs are medicines that control nausea—a feeling of sickness or queasiness in the stomach
with an urge to vomit. These drugs also prevent or stop
vomiting. Drugs that control vomiting are called antiemetic drugs.

Description

Blurred vision, diarrhea, cramps, headache

KEY TERMS

Definition

Another commonly prescribed antinausea drug is
promethazine (Phenergan). Promethazine also may be
prescribed to relieve allergy symptoms and apprehension, as well as motion sickness.

Possible Common Side Effects Include:
Involuntary muscle spasms, dizziness,
jitteriness, puckering of the mouth
Dizziness, dry mouth, nausea and vomiting,
rash
Fatigue, drowsiness, restlessness

Tranquilizer—Medicine that has a calming effect
and is used to treat anxiety and mental tension.



Syrup—5-10 mg three to four times a day



Injection—5-10 mg injected into a muscle three to
four times a day.

Doses for children must be determined by a
physician.
Promethazine may be administered in pill, syrup,
chewable tablet, or extended release capsule form by
prescription only. For severe nausea, it may be administered by injection or via a suppository. The physician
recommends dose depending on the patient’s condition.

Precautions
Prochlorperazine may cause a movement disorder
called tardive dyskinesia. Signs of this disorder are
involuntary twitches and muscle spasms in the face
and body and jutting or rolling movements of the
tongue. The condition may be permanent. Older people,
especially women, are particularly at risk of developing
this problem when they take prochlorperazine.
329

Antinausea drugs

Abnormal results

Antinausea drugs

Some people feel drowsy, dizzy, lightheaded, or less
alert when using this medicine. The drug may also cause
blurred vision, and movement problems. For these reasons, anyone who takes this drug should not drive, use
machines or do anything else that might be dangerous
until they have found out how the drug affects them.
Prochlorperazine makes some people sweat less,
which can allow the body to overheat. The drug may
also make the skin and eyes more sensitive to the sun.
People who are taking prochlorperazine should try to
avoid extreme heat and exposure to the sun. When
going outdoors, they should wear protective clothing,
a hat, a sunscreen with a skin protection factor (SPF)
of at least 15, and sunglasses that block ultraviolet
(UV) light. Saunas, sunlamps, tanning booths, tanning beds, hot baths, and hot tubs should be avoided
while taking this medicine. Anyone who must be
exposed to extreme heat while taking the drug should
check with his or her physician.
This medicine adds to the effects of alcohol and
other drugs that slow down the central nervous system, such as antihistamines, cold and flu medicines,
tranquilizers, sleep aids, anesthetics, some pain medicines, and muscle relaxants. Drinking alcohol while
taking prochlorperazine is not advised and patients
should check with the physician who prescribed the
drug before combining it with any other medicines.
Do not stop taking this medicine without checking
with the physician who prescribed it. Stopping the drug
suddenly can cause dizziness, nausea, vomiting, tremors,
and other side effects. When stopping the medicine, it
may be necessary to taper down the dose gradually.
Prochlorperazine may cause false pregnancy tests.
Women who are pregnant (or planning to become
pregnant) or breast feeding should check with their
physicians before using antinausea medicines.
Before using prochlorperazine, people with any of
the medical problems should make sure their physicians are aware of their conditions:


Previous sensitivity
prochlorperazine

or

allergic

reaction



Heart disease



Glaucoma



Brain tumor



Intestinal blockage



Abnormal blood conditions, such as leukemia



Exposure to pesticides.

to

Some people may experience side effects from
promethazine including:
330



dry mouth



drowsiness



confusion



fatigue



difficulty coordinating movements



stuffy nose.

A physician should be contacted immediately if a
patient experiences the following effects while taking
promethazine:


vision problems



ringing in the ears



tremors



insomnia



excitement



restlessness



yellowing of the skin or eyes



skin rash.

Side effects
Many side effects are possible with prochlorperazine, including, but not limited to, constipation, dizziness, drowsiness, decreased sweating, dry mouth, stuffy
nose, movement problems, changes in menstrual period,
increased sensitivity to sun, and swelling or pain in
breasts. Anyone who has unusual or troublesome symptoms after taking prochlorperazine should get in touch
with his or her physician.
Side effects associated with promethazine include
those listed above and interactions with various medications that may cause complications or lessen the
effects of the drug. A physician should be notified of
other medications the patient is on when taking
promethazine.

Interactions
Prochlorperazine may interact with other medicines. When this happens, the effects of one or both of
the drugs may change or the risk of side effects may be
greater. Among the drugs that may interact with prochlorperazine are antiseizure drugs such as phenytoin
(Dilantin) and carbamazepine (Tegretol), anticoagulants such as warfarin (Coumadin), and drugs that
slow the central nervous system such as alprazolam
(Xanax), diazepam (Valium), and secobarbital
(Seconal). Not every drug that interacts with prochlorperazine is listed here. A physician or pharmacist can
advise patients about prescription or nonprescription
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

Flake, Zachary A., Robert D. Scalley, and Austin G. Bailey.
‘‘Practical Selection of Antiemetics.’’ American Family
Physician March 1, 2004: 1169.
OTHER

‘‘Promethazine’’ Medline Plus Drug Information. <http://
www.nlm.nih.gov/medlineplus/druginfo/medmaster/
a682284.html#precautions>.

Nancy Ross-Flanigan
Teresa G. Odle

KEY TERMS
Antibody—A special protein built by the immune
system as a defense against foreign material entering the body.
Autoantibody—An antibody that attacks the body’s
own cells or tissues.
Antinuclear antibodies—Autoantibodies that attack
substances found in the center, or nucleus, of all
cells.
Autoimmune disease—Disease in which the body
makes antibodies against its own cells or tissues.
Titer—A dilution of a substance with an exact
known amount of fluid. For example, one part of
serum diluted with four parts of saline is a titer of 1:4.

I Antinuclear antibody test
Definition
The antinuclear antibody (ANA) test is a test done
early in the evaluation of a person for autoimmune or
rheumatic disease, particularly systemic lupus erythematosus (SLE).

Purpose
In autoimmune diseases, the body makes antibodies that work against its own cells or tissues.
Rheumatic diseases (diseases that affect connective
tissue, including the joints, bone, and muscle) are
also associated with these antibodies. Autoantibodies
are proteins built by the body, but instead of guarding
against foreign material (including bacteria, viruses,
and fungi) as normal antibodies do, they attack the
body’s own cells.
Autoimmune and rheumatic diseases can be difficult to diagnose. People with the same disease can
have very different symptoms. A helpful strategy in
the diagnosis of these diseases is to find and identify an
autoantibody in the person’s blood.
The antinuclear antibody test looks for a
group of autoantibodies that attack substances
found in the center (nucleus) of all cells. It is useful
as a screen for many autoantibodies associated
with diseases that affect the entire body (systemic
diseases).
This test is particularly useful when diagnosing a
person with symptoms of SLE, an illness that affects
many body organs and tissues. If the test is negative, it
is unlikely that the person has SLE; if the test is positive,
GALE ENCYCLOPEDIA OF MEDICINE

more tests are done to confirm whether the person has
SLE or another related disease. Other diseases, such as
scleroderma, Sjögren’s syndrome, Raynaud’s disease,
rheumatoid arthritis, and autoimmune hepatitis, often
have a positive test for antinuclear antibodies.

Description
Five to 10 mL of blood is needed for this test. The
antinuclear antibody test is done by adding a person’s
serum to commercial cells mounted on a microscope
slide. If antinuclear antibodies are in the serum, they
bind to the nuclei of cells on the slide. Next, a second
antibody is added to the mixture. This antibody is
‘‘tagged’’ with a fluorescent dye so that it can be
seen. The second antibody attaches to any antibodies
and cells bound together and, because of the fluorescent ‘‘tag,’’ the areas with antinuclear antibodies seem
to glow, or fluoresce, when the slide is viewed under an
ultraviolet microscope.
If fluorescent cells are seen, the test is positive.
When positive, the serum is diluted, or titered, and
the test done again. These steps are repeated until the
serum is so dilute it no longer gives a positive result.
The last dilution that shows fluorescence is the titer
reported.
The pattern of fluorescence within the cells gives
the physician clues as to what the disease might be.
The test result includes the titer and the pattern.
This test is also called the fluorescent antinuclear
antibody test or FANA. Results are available within
one to three days.
331

Antinuclear antibody test

(over-the-counter) drugs that might interact with
Prochlorperazine.

Antiparkinson drugs

Preparation
No special preparations or diet changes are
required before a person undergoes an antinuclear
antibody test.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops reduces bruising. Warm packs relieve discomfort.

Normal results

Antiparkinson Drugs

Brand Name (Generic
Name)
Artane (trihexyphenidyl
hydrochloride)
Benadryl (diephenhydramine hydrochloride)
Cogentin (benztropine
mesylate)
Eldepryl (selegiline
hydrochloride)
Parlodel (bromocriptine
mesylate)
Sinemet CR

Possible Common Side Effects Include:
Dry mouth, nervousness, blurred vision,
nausea
Dizziness, sleepiness, upset stomach,
decreased coordination
Constipation, dry mouth, nausea and
vomiting, rash
Abdominal and back pain, drowsiness,
decreased coordination
Constipation, decreased blood pressure,
abdominal cramps
Involuntary body movements, confusion,
nausea, hallucinations

Normal results will be negative, showing no antinuclear antibodies.

Abnormal results
A positive test in a person with symptoms of an
autoimmune or rheumatic disease helps the physician
make a diagnosis. More than 95% of people with SLE
have a positive ANA test. Scleroderma has a 60-71%
positive rate; Sjögren’s disease, 50-60%, and rheumatoid arthritis, 25-30%.
Several factors must be considered when interpreting a positive test. Diseases other than autoimmune diseases can cause autoantibodies. Some
healthy people have a positive test. More testing
is done after a positive test to identify individual
autoantibodies associated with the various diseases.
Resources

arms, legs, jaw, and face; stiffness or rigidity of the
arms, legs, and trunk; slowness of movement (bradykinesia); and poor balance and coordination. Parkinson’s
disease is the most common form of parkinsonism and
is seen more frequently with advancing age. Other
forms of the disorder may result from viral infections,
environmental toxins, carbon monoxide poisoning, and
the effects of treatment with antipsychotic drugs.
The immediate cause of Parkinson’s disease or
Parkinsonian-like syndrome is the lack of the neurotransmitter dopamine in the brain. Drug therapy may
take several forms, including replacement of dopamine, inhibition of dopamine metabolism to increase
the effects of the dopamine already present, or sensitization of dopamine receptors. Drugs may be used
singly or in combination.

BOOKS

Lehman, Craig A. Saunders Manual of Clinical Laboratory
Science. Philadelphia: W. B. Saunders Co., 1998.

Nancy J. Nordenson

I Antiparkinson drugs
Definition
Antiparkinson drugs are medicines that relieve the
symptoms of Parkinson’s disease and other forms of
parkinsonism.

Purpose
Antiparkinson drugs are used to treat symptoms of
parkinsonism, a group of disorders that share four
main symptoms: tremor or trembling in the hands,
332

Description
Levodopa (Larodopa) is the mainstay of
Parkinson’s treatment. The drug crosses the bloodbrain barrier, and is converted to dopamine. The drug
may be administered alone, or in combination with
carbidopa (Lodosyn) which inhibits the enzyme responsible for the destruction of levodopa. The limitation of
levodopa or levodopa-carbidopa therapy is that after
approximately two years of treatment, the drugs cease
to work reliably. This has been termed the ‘‘on-off phenomenon.’’ Additional treatment strategies have been
developed to retard the progression of Parkinsonism,
or to find alternative approaches to treatment.
Anticholinergic drugs reduce some of the symptoms of Parkinsonism, and reduce the reuptake of
dopamine, thereby sustaining the activity of the natural neurohormone. They may be effective in all stages
of the disease. All drugs with anticholinergic
GALE ENCYCLOPEDIA OF MEDICINE

Anorexia—Lack or loss of appetite.
Anticholigerginc—An agent that blocks the parasympathetic nerves and their actions.
Bradykinesia—Extremely slow movement.
Bruxism—Compulsive grinding or clenching of the
teeth, especially at night.
Carbon monoxide—A colorless, odorless, highly
poisonous gas.
Central nervous system—The brain and spinal cord.
Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Hallucination—A false or distorted perception
of objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Heat stroke—A severe condition caused by prolonged exposure to high heat. Heat stroke interferes
with the body’s temperature regulating abilities and
can lead to collapse and coma.
Parkinsonism—A group of conditions that all have
these typical symptoms in common: tremor, rigidity, slow movement, and poor balance and
coordination.
Pregnancy category— A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category
B: Animal studies indicate no fetal risk, but no
human studies; or adverse effects in animals, but
not in well-controlled human studies. Category C:
No adequate human or animal studies; or adverse
fetal effects in animal studies, but no available
human data. Category D: Evidence of fetal risk,
but benefits outweigh risks. Category X: Evidence
of fetal risk. Risks outweigh any benefits.
Seizure—A sudden attack, spasm, or convulsion.
Spasm—Sudden, involuntary tensing of a muscle or
a group of muscles.
Tremor—Shakiness or trembling.

properties, the naturally occurring belladonna alkaloids (atropine, scopolamine, hyoscyamine), some
antihistamines with anticholinergic properties, and
synthetics such as benztropin (Cogentin), procyclidine
(Kemadrin) and biperiden (Akineton) are members of
GALE ENCYCLOPEDIA OF MEDICINE

this group. Although the anticholinergic drugs have only
limited activity against Parkinson’s disease, they are
useful in the early stages, and may be adjuncts to levodopa as the disease progresses.
Amantadine (Symmetrel), was developed for prevention of influenza virus infection, but has antiParkinsonian properties. Its mechanism of action is
not known.
Bromocriptine (Parlodel) is a prolactin inhibitor,
which is used for a variety of indications including
amenorrhea/galactorrhea, female infertility, and acromegaly. It appears to work by direct stimulation of the
dopamine receptors. Bromocriptine is used as a late
adjunct to levodopa therapy, and may permit reduction in levodopa dosage. Pergolide (Permax) is similar
to bromocriptine, but has not been studied as extensively in Parkinson’s disease.
Entacapone (Comtan) appears to act by maintaining levels of dopamine through enzyme inhibition. It is used as an adjunct to levodopa was the
patient is beginning to experience the on-off effect.
Tolcapone (Tasmar) is a similar agent, but has
demonstrated the potential for inducing severe
liver failure. As such, tolcapone is reserved for
cases where all other adjunctive therapies have
failed or are contraindicated.
Selegeline (Carbex, Eldepryl) is a selective monoamine oxidase B (MAO-B) inhibitor, however its
mechanism of action in Parkinsonism is unclear,
since other drugs with MAO-B inhibition have failed
to show similar anti-Parkinsonian effects. Selegeline is
used primarily as an adjunct to levodopa, although
some studies have indicated that the drug may be
useful in the early stages of Parkinsonism, and may
delay the progression of the disease.
Pramipexole (Mirapex) and ropinirole (Requip)
are believed to act by direct stimulation of the dopamine receptors in the brain. They may be used alone in
early Parkison’s disease, or as adjuncts to levodopa in
advanced stages.

Recommended dosage
Dosages of anti-Parkinsonian medications must
be highly individualized. All doses must be carefully
titrated. Consult specific references.

Precautions
There are a large number of drugs and drug
classes used to treat Parkinson’s disease, and individual references should be consulted.
333

Antiparkinson drugs

KEY TERMS

Antiprotozoal drugs

The anticholinergics have a large number of
adverse effects, all related to their primary mode of
activity. Their cardiovascular effects include tachycardia, palpitations, hypotension, postural hypotension,
and mild bradycardia. They may also cause a wide
range of central nervous system effects, including
disorientation, confusion, memory loss, hallucinations,
psychoses, agitation, nervousness, delusions, delirium,
paranoia, euphoria, excitement, lightheadedness,
dizziness, headache, listlessness, depression, drowsiness,
weakness, and giddiness. Dry mouth, dry eyes and
gastrointestinal distress are common problems.
Sedation has been reported with some drugs in this
group, but this may be beneficial in patients who suffer
from insomnia. Pregnancy risk factor is C. Because
anticholinergic drugs may inhibit milk production,
their use during breastfeeding is not recommended.
Patients should be warned that anticholinergic medications will inhibit perspiration, and so exercise during
periods of high temperature should be avoided.
Levodopa has a large number of adverse effects.
Anorexia, loss of appetite, occurs in roughly half the
patients using this drug. Symptoms of gastrointestinal
upset, such as nausea and vomiting, have been reported
in 80% of cases. Other reported effects include
increased hand tremor; headache; dizziness; numbness;
weakness and faintness; bruxism; confusion; insomnia; nightmares; hallucinations and delusions; agitation and anxiety; malaise; fatigue and euphoria.
Levodopa has not been listed under the pregnancy
risk factor schedules, but should be used with caution.
Breastfeeding is not recommended.
Amantadine is generally well tolerated, but may
cause dizziness and nausea. It is classified as pregnancy
schedule C. Since amantadine is excreted in breast
milk, breastfeeding while taking amantidine is not
recommended.
Pergolide and bromocriptine have been generally
well tolerated. Orthostatic hypotension are common
problems, and patients must be instructed to risk
slowly from bed. This problem can be minimized by
low initial doses with small dose increments.
Hallucinations may be a problem. Bromocriptine has
not been evaluated for pregnancy risk, while pergolide
is category B. Since both drugs may inhibit lactation,
breastfeeding while taking these drugs is not
recommended.
Pramipexole and ropinirole cause orthostatic
hypotension, hallucinations and dizziness. The two
drugs are in pregnancy category C. In animals, ropinirole has been shown to have adverse effects on
embryo-fetal development, including teratogenic
334

effects, decreased fetal body weight, increased fetal
death and digital malformation. Because these drugs
inhibit prolactin secretion, they should not be taken
while breastfeeding.

Side effects
The most common side effects are associated with
the central nervous system, and include dizziness,
lightheadedness, mood changes and hallucinations.
Gastrointestinal problems, including nausea and
vomiting, are also common.

Interactions
All anti-Parkinsonian regimens should be carefully reviewed for possible drug interactions. Note
that combination therapy with anti-Parkinsonian
drugs is, in itself, use of additive and potentiating
interactions between drugs, and so careful dose adjustment is needed whenever a drug is added or
withdrawn.
Samuel D. Uretsky, PharmD

Antiplatelet drugs see Anticoagulant
and antiplatelet drugs

I Antiprotozoal drugs
Definition
Antiprotozoal drugs are medicines that treat
infections caused by protozoa.

Purpose
Antiprotozoal drugs are used to treat a variety of
diseases caused by protozoa. Protozoa are animallike, one-celled animals, such as amoebas. Some are
parasites that cause infections in the body. African
sleeping sickness, giardiasis, amebiasis, Pneumocystis
carinii pneumonia (PCP), and malaria are examples of
diseases caused by protozoa.

Description
Antiprotozoal drugs come in liquid, tablet, and
injectable forms and are available only with a doctor’s
prescription. Some commonly used antiprotozoal
drugs are metronidazole (Flagyl), eflornithine
GALE ENCYCLOPEDIA OF MEDICINE

Amebiasis—An infection caused by an ameba,
which is a type of protozoan.
Fetus—A developing baby inside the womb.
Giardiasis—A condition in which the intestines are
infected with Giardia lamblia, a type of protozoan.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Parasite—An organism that lives and feeds in or on
another organism (the host) and does nothing to
benefit the host.
Pneumocystis carinii pneumonia—A severe
lung infection caused by a parasitic protozoan.
The disease mainly affects people with weakened
immune systems, such as people with AIDS.

(Ornidyl), furazolidone (Furoxone), hydroxychloroquine (Plaquenil), iodoquinol (Diquinol, Yodoquinol,
Yodoxin), and pentamidine (Pentam 300).

Recommended dosage
The recommended dosage depends on the type of
antiprotozoal drug, its strength, and the medical problem for which it is being used. Check with the physician who prescribed the drug or the pharmacist who
filled the prescription for the correct dosage. Always
take antiprotozoal drugs exactly as directed.

Precautions
Some people feel dizzy, confused, lightheaded, or
less alert when using these drugs. The drugs may also
cause blurred vision and other vision problems. For
these reasons, anyone who takes these drugs should
not drive, use machines or do anything else that might
be dangerous until they have found out how the drugs
affect them.

The physician should also be told about any allergies
to foods, dyes, preservatives, or other substances.
Some antiprotozoal drugs may cause problems with
the blood. This can increase the risk of infection or
excessive bleeding. Patients taking these drugs shouldbe
careful not to injure their gums when brushing or flossing their teeth or using a toothpick. They shouldcheck
with the physician before having any dentalwork done.
Care should also be taken to avoidcuts from razors, nail
clippers, or kitchen knives, orhousehold tools. Anyone
who has any of these symptoms while taking antiprotozoal drugs should call the physician immediately:


Fever or chills



Signs of cold or flu



Signs of infection, such as redness, swelling, or
inflammation



Unusual bruising or bleeding



Black, tarry stools



Blood in urine or stools



Pinpoint red spots on the skin



Unusual tiredness or weakness.

Anyone taking this medicine should also check with
a physician immediately if any of these symptoms occur:


Blurred vision or other vision changes



Skin rash, hives, or itching



Swelling of the neck



Clumsiness or unsteadiness



Numbness, tingling, pain, or weakness in the hands
or feet



Decrease in urination.

Children are especially sensitive to the effects of
some antiprotozoal drugs. Never give this medicine to a
child unless directed to do so by a physician, and always
keep this medicine out of the reach of children. Use
safety vials.

The antiprotozoal drug furazolidone may cause
very dangerous side effects when taken with certain
foods or beverages. Likewise, metronidazole (Flagyl)
can cause serious liver damage if taken with alcohol.
Check with the physician who prescribed the drug or
the pharmacist who filled the prescription for a list of
products to avoid while taking these medicines.

The effects of antiprotozoal drugs on pregnant
women have not been studied. However, in experiments with pregnant laboratory animals, some antiprotozoal drugs cause birth defects or death of the
fetus. Women who are pregnant or who plan to
become pregnant should check with their physicians
before taking antiprotozoal drugs. Mothers who are
breastfeeding should also check with their physicians
about the safety of taking these drugs.

Anyone who has ever had unusual reactions to
antiprotozoal drugs or related medicines should let his
or her physician know before taking the drugs again.

Before using antiprotozoal drugs, people with any
of these medical problems should make sure their
physicians are aware of their conditions:

GALE ENCYCLOPEDIA OF MEDICINE

335

Antiprotozoal drugs

KEY TERMS

Antipsychotic drugs



Anemia or other blood problems



Kidney disease



Heart disease



Low blood pressure



Diabetes



Hypoglycemia (low blood sugar)



Liver disease



Stomach or intestinal disease



Nerve or brain disease or disorder, including convulsions (seizures)



Psoriasis (a skin condition)



Hearing loss



Deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD)



Eye or vision problems



Thyroid disease.

Side effects
The most common side effects are diarrhea, nausea, vomiting, and stomach pain. These problems
usually go away as the body adjusts to the drug and
do not require medical treatment.
Other rare side effects may occur. Anyone who
has unusual symptoms after taking an antiprotozoal drug should get in touch with his or her
physician.

Interactions
Antiprotozoal drugs may interact with other medicines. When this happens, the effects of one or both of
the drugs may change or the risk of side effects may be
greater. Anyone who takes antiprotozoal drugs should
let the physician know all other medicines he or she is
taking. Among the drugs that may interact with antiprotozoal drugs are:


Alcohol



Anticancer drugs



Medicine for overactive thyroid



Antiviral drugs such as zidovudine (Retrovir)



Antibiotics



Medicine used to relieve pain or inflammation



Amphetamine



Diet pills (appetite suppressants)

336



Monoamine oxidase inhibitors (MAO inhibitors)
such as phenelzine (Nardil) and tranylcypromine
(Parnate), used to treat conditions including depression and Parkinson’s disease.



Tricyclic antidepressants such as amitriptyline
(Elavil) and imipramine (Tofranil)



Decongestants such as phenylephrine (NeoSynephrine) and pseudoephedrine (Sudafed)



Other antiprotozoal drugs.

The list above does not include every medicine
that may interact with an antifungal drug. Be sure
to check with a physician or pharmacist before
combining antifungal drugs with any other prescription or nonprescription (over-the-counter)
medicine.
Nancy Ross-Flanigan

Antipruritic drugs see Anti-itch drugs

I Antipsychotic drugs
Definition
Antipsychotic drugs are a class of medicines used
to treat psychosis and other mental and emotional
conditions.

Purpose
Psychosis is defined as ‘‘a serious mental disorder
(as schizophrenia) characterized by defective or lost
contact with reality often with hallucinations or delusions.’’ Psychosis is an end-stage condition arising
from a variety of possible causes. Anti-psychotic
drugs control the symptoms of psychosis, and in
many cases are effective in controlling the symptoms
of other disorders that may lead to psychosis, including bipolar mood disorder (formerly termed manicdepressive), in which the patient cycles from severe
depression to feelings of extreme excitation. This
class of drugs is primarily composed of the major
tranquilizers; however, lithium carbonate, a drug
that is largely specific to bipolar mood disorder, is
commonly classified among the antipsychotic agents.

Description
The antipsychotic agents may be divided by chemical class. The phenothiazines are the oldest group,
and include chlorpromazine (Thorazine), mesoridazine
GALE ENCYCLOPEDIA OF MEDICINE

Brand Name (Generic
Name)
Clozaril (clozapine)
Compazine
(prochlorperazine)
Haldol (haloperidol)

Mellaril (thioridazine)
Navane (thiothixene)
Risperdal
(risperidone)
Stelazine (trifluoperazine hydrochloride)
Thorazine
(chlorpromazine)
Triavil

Possible Common Side Effects Include:
Seizures, agranulocytosis, dizziness,
increased blood pressure
Involuntary muscle spasms, dizziness,
jitteriness, puckering of the mouth
Involuntary muscle spasms, blurred vision,
dehydration, headache, puckering of the
mouth
Involuntary muscle spasms, constipation and
diarrhea, sensitivity to light
Involuntary muscle spasms, dry mouth, rash,
hives
Involuntary muscle spasms, abdominal and
chest pain, fever, headache
Involuntary muscle spasms, drowsiness,
fatigue
Involuntary muscle spasms, labored breathing,
fever, puckering of the mouth
Involuntary muscle spasms, disorientation,
excitability, lightheadedness

(Serentil), prochlorperazine (Compazine), and thioridazine (Mellaril). These drugs are essentially similar in
action and adverse effects. They may also be used as
anti-emetics, although prochlorperazine is the drug
most often used for this indication.
The phenylbutylpiperadines are haloperidol
(Haldol) and pimozide (Orap). They find primary
use in control of Tourette’s syndrome. Haloperidol
has been extremely useful in controlling aggressive
behavior.
The debenzapine derivatives, clozapine (Clozaril),
loxapine (Loxitane), olanzapine (Zyprexa) and quetiapine (Seroquel), have been effective in controlling psychotic symptoms that have not been responsive to
other classes of drugs.
The benzisoxidil group is composed of resperidone
(Resperidal) and ziprasidone (Geodon). Resperidone
has been found useful for controlling bipolar mood
disorder, while ziprasidone is used primarily as second-line treatment for schizophrenia.
In addition to these drugs, the class of antipsychotic agents includes lithium carbonate (Eskalith,
Lithonate), which is used for control of bipolar
mood disorder, and thiothixene (Navane), which is
used in the treatment of psychosis.

Newer agents
Some newer antipsychotic drugs have been
approved by the Food and Drug administration
GALE ENCYCLOPEDIA OF MEDICINE

Agranulocytosis—An acute condition marked by
severe depression of the bone marrow, which produces white blood cells, and by prostration, chills,
swollen neck, and sore throat sometimes with local
ulceration. Aalso called agranulocytic angina or
granulocytopenia.
Anticholinergic—Blocking the action of the neurohormone acetylcholine. The most obvious effects
include dry mouth and dry eyes.
Anticonvulsants—A class of drugs given to control
seizures.
Pregnancy category—A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B: Animal
studies indicate no fetal risk, but no human studies,
or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate
human or animal studies, or adverse fetal effects in
animal studies, but no available human data.
Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks
outweigh any benefits.

(FDA) in the early 2000s. These drugs are sometimes
called second-generation antipsychotics or SGAs.
Aripiprazole (Abilify), which is classified as a partial
dopaminergic agonist, received FDA approval in
August 2003. Two drugs that are still under investigation, a neurokinin antagonist and a serotonin 2A/2C
antagonist respectively, show promise in the treatment
of schizophrenia and schizoaffective disorder.

Recommended dosage
Dose varies with the drug, condition being treated, and patient response. See specific references.

Precautions
Neuroleptic malignant syndrome (NMS). NMS is
a rare, idiosyncratic combination of extra-pyramidal
symptoms (EPS), hyperthermia, and autonomic disturbance. Onset may be hours to months after drug
initiation, but once started, proceeds rapidly over
24 to 72 hours. It is most commonly associated with
haloperidol, long-acting fluphenazine, but has occurred
with thiothixene, thioridazine, and clozapine, and may
337

Antipsychotic drugs

KEY TERMS

Antipsychotic Drugs

Antipsychotic drugs

occur with other agents. NMS is potentially fatal, and
requires intensive symptomatic treatment and immediate discontinuation of neuroleptic treatment. There is
no established treatment. Most patients who develop
NMS will have the same problem if the drug is
restarted.
Agranulocytosis has been associated with clozapine. This is a potentially fatal reaction, but can be
prevented with careful monitoring of the white blood
count. There are no well-established risk factors for
developing agranulocytosis, and so all patients treated
with this drug must follow the clozapine Patient
Management System. For more information, the
reader should call 1-800-448-5938.
Anticholinergic effects, particularly dry mouth,
have been reported with all of the phenothiazines,
and can be severe enough to cause patients to discontinue their medication.
Photosensitization is a common reaction to chlorpromazine. Patients must be instructed to use precautions when exposed to sunlight.
Lithium carbonate commonly causes increased
frequency of urination.
The so-called atypical antipsychotics are associated with a substantial increase in the risk of developing diabetes mellitus. A study done at the University
of Rochester (New York) reported in 2004 that 15.2%
of patients receiving atypical antipsychotics developed
diabetes, compared with 6.3% of patients taking other
antipsychotic medications.
Antipsychotic drugs are pregnancy category C.
(Clozapine is category B.) The drugs in this class
appear to be generally safe for occasional use at low
doses during pregnancy, but should be avoided near
time of delivery. Although the drugs do not appear
to be teratogenic, when used near term, they may
cross the placenta and have adverse effects on the
newborn infant, including causing involuntary
movements. There is no information about safety
in breast feeding.
As a class, the antipsychotic drugs have a large
number of potential side effects, many of them serious.
Because of the potential severity of side effects, these
drugs must be used with special caution in children.
Specific references should be consulted.

Interactions
Because the phenothiazines have anticholinergic
effects, they should not be used in combination with
other drugs that may have similar effects.
338

Because the drugs in this group may cause hypotension, or low blood pressure, they should be used
with extreme care in combination with blood pressurelowering drugs.
The antipsychotic drugs have a large number of
drug interactions. Consult specific references.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Childhood Psychosis.’’ Section 19, Chapter 274 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2002.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychiatric Emergencies.’’ Section 15, Chapter 194
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Wilson, Billie Ann, Margaret T. Shannon, and Carolyn L.
Stang. Nurse’s Drug Guide 2003. Upper Saddle River,
NJ: Prentice Hall, 2003.
PERIODICALS

DeLeon, A., N. C. Patel, and M. L. Crismon. ‘‘Aripiprazole:
A Comprehensive Review of Its Pharmacology, Clinical
Efficacy, and Tolerability.’’ Clinical Therapeutics 26
(May 2004): 649–666.
Emsley, R., H. J. Turner, J. Schronen, et al. ‘‘A Single-Blind,
Randomized Trial Comparing Quetiapine and
Haloperidol in the Treatment of Tardive Dyskinesia.’’
Journal of Clinical Psychiatry 65 (May 2004): 696–701.
Lamberti, J. S., J. F. Crilly, K. Maharaj, et al. ‘‘Prevalence of
Diabetes Mellitus among Outpatients with Severe Mental
Disorders Receiving Atypical Antipsychotic Drugs.’’
Journal of Clinical Psychiatry 65 (May 2004): 702–706.
Meltzer, H. Y., L. Arvanitis, D. Bauer, et al. ‘‘PlaceboControlled Evaluation of Four Novel Compounds for
the Treatment of Schizophrenia and Schizoaffective
Disorder.’’ American Journal of Psychiatry 161 (June
2004): 975–984.
Stahl, S. M. ‘‘Anticonvulsants as Mood Stabilizers and
Adjuncts to Antipsychotics: Valproate, Lamotrigine,
Carbamazepine, and Oxcarbazepine and Actions at
Voltage-Gated Sodium Channels.’’ Journal of Clinical
Psychiatry 65 (June 2004): 738–739.
ORGANIZATIONS

American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814. (301)
657-3000. <http://www.ashp.org>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <http://www.fda.gov>.

Samuel D. Uretsky, PharmD
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
The atypical antipsychotic agents, sometimes
called the ‘‘novel’’ antipsychotic agents are a group
of drugs which are different chemically from the older
drugs used to treat psychosis. The ‘‘conventional’’
antipsychotic drugs are classified by their chemical
structures as the phenothiazines, thioxanthines
(which are chemically very similar to the phenothiazines), butyrophenones, diphenylbutylpiperadines
and the indolones. All of the atypical antipsychotic
agents are chemically classified as dibenzepines. They
are considered atypical or novel because they have
different side effects from the conventional antipsychotic agents. The atypical drugs are far less likely to
cause extra-pyrammidal side-effects(EPS), drug
induced involuntary movements, than are the older
drugs. The atypical antipsychotic drugs may also be
effective in some cases that are resistant to older drugs.
The drugs in this group are clozapine (Clozaril),
loxapine (Loxitane), olanzapine (Zyprexa), and quetiapine (Seroquel).

KEY TERMS
Anxiety—An abnormal and overwhelming sense of
apprehension and fear often marked by physiological
signs (as sweating, tension, and increased pulse), by
doubt concerning the reality and nature of the threat,
and by self-doubt about one’s capacity to cope with it.
Delusions—A false belief regarding the self or persons or objects outside the self that persists despite
the facts.
Depression—A state of being depressed marked
especially by sadness, inactivity, difficulty with
thinking and concentration, a significant increase or
decrease in appetite and time spent sleeping, feelings
of dejection and hopelessness, and sometimes suicidal thoughts or an attempt to commit suicide.
Glucocorticoid—Any of a group of corticosteroids
(as hydrocortisone or dexamethasone) that are antiinflammatory and immunosuppressive, and that
are used widely in medicine (as in the alleviation
of the symptoms of rheumatoid arthritis).
Psychosis—A serious mental disorder characterized by defective or lost contact with reality often
with hallucinations or delusions.

Purpose
The antipsychotic drugs are used to treat severe
emotional disorders. Although there may be different
names for these disorders, depending on severity and
how long the symptoms last, psychotic disorders all
cause at least one of the following symptoms:
Loxapine has also been used to treat anxiety with
mental depression.

Recommended dosage
The recommended dose depends on the drug, the
patient, and the condition being treated. The normal
practice is to start each patient at a low dose, and
gradually increase the dose until a satisfactory
response is achieved. The odse should be held at the
lowest level that gives satisfactory results.
Clozapine usually requires doses between 300 and
600 milligrams a day, but some people require as much
as 900 milligrams/day. Doses higher than 900 millgrams/day are not recommended.
Loxapine is usually effective at doses of 60-100
milligrams/day, but may be used in doses as high as
250 mg/day if needed.
Olanzapine doses vary with the condition being
treated. The usual maximum dose is 20 milligrams/day.
GALE ENCYCLOPEDIA OF MEDICINE

Quetiapine may be dosed anywhere from 150-750
milligrams/day, depending on how well the patient
responds.

Precautions
Although the atypical antipsychotics are generally
safe, clozapine has been associated with severe agranulocytosis, a shortage of white blood cells. For this
reason, people who may be treated with clozapine
should have blood counts before starting the drug,
blood counts every week for as long as they are using
clozapine, and blood counts every week for the first
4 weeks after they stop taking clozapine. If there is any
evidence of a drop in the white blood count while using
clozapine, the drug should be stopped.
Atypical antipsychotics should not be used in
patients with liver damage, brain or circulatory problems, or some types of blood problems.
Allergies
People who have had an allergic reaction to one of
the atypical antipsychotics should not use that
339

Antipsychotic drugs, atypical

I Antipsychotic drugs, atypical

Anti-rejection drugs

medication again. However, sometimes it is possible to
use a different drug from the same group safely.

Definition

Pregnancy
The atypical antipsychotics have not been proved
safe in pregnancy. They should be used only when
clearly needed and when potential benefits outweigh
potential hazards to the fetus. These drugs have not
been reported in human milk.

Side effects
Although the atypical antipsychotics are less
likely to cause involuntary movements than the older
antipsychotic drugs, they still have a large number of
adverse effects. The following list is not complete.
Review each drug individually for a full list of possible
adverse effects.

Interactions
Taking atypical antipsychotic medications with
certain other drugs may affect the way the drugs work
or may increase the chance of side effects. While taking
antipsychotic drugs, do not take any other prescription
or nonprescription (over-the-counter) drugs without
first checking with a physician.
Because the atypical antipsychotics may cause
lowering of blood pressure, care should be used when
these drugs are taken at the same time as other drugs
which lower blood pressure.
Quetiapine has many interactions. Doses should
be carefully adjusted when quetiapine is used with
ketoconazole, itraconazole, fluconazole, erythromycin, carbamazepine, barbiturates, rifampin or glucocorticoids including prednisone, dexamethasone and
methylprednisolone.
These drugs will also require dose adjustments
when used with anti-Parkinson medications.
Resources
BOOKS

Brain Basics: An Integrated Biological Approach to
Understanding and Assessing Human Behavior. Phoenix:
Biological-Psychiatry-Institute, June 1999.
PERIODICALS

McDougle, C. J. ‘‘A double-blind, placebo-controlled study
of risperidone addition in serotonin reuptake inhibitorrefractory obsessive-compulsive disorder.’’ Archives of
General Psychiatry August 2000: 794.

Samuel D. Uretsky, PharmD
340

I Anti-rejection drugs
Anti-rejection drugs are daily medications taken by
organ transplant patients to prevent organ rejection.

Purpose
Anti-rejection drugs, which are also called immunosuppressants, help to suppress the immune system’s
response to a new organ. When a new organ is placed
inside a patient s body, the patient’s immune system
recognizes the organ as foreign tissue and tries to reject it.

Description
When a physician prescribes anti-rejection drugs,
the patient’s risk of rejection and susceptibility to side
effects are considered. The most common drugs prescribed to prevent organ rejection are cyclosporine,
prednisone, azathioprine, tacrolimus or FK506,
mycophenolate mofetil, sirolimus, and OKT3, as well
as ATGAM and Thymoglobulin. As is true with all
medications, each of these drugs has benefits and
drawbacks. Cyclosporine, which is one of the most
frequently used anti-rejection drugs, is usually combined with prednisone. An extremely powerful medicine, cyclosporine is usually taken by a patient over the
course of his or her lifetime. Cortisol, which is the
naturally produced form of prednisone in a person’s
body, helps the body manage stress, such as infections
or organ rejection. Taking prednisone results in less
cortisol production in a person’s body, thus minimizing
the risk of rejection. Azathioprine, which needs to be
taken with food to avoid stomach upset, is frequently
combined with cyclosporine, prednisone, or tacrolimus.
Mycophenolate mofetil is a relatively new immunosuppressant that is similar to azathioprine; therefore, the
two drugs should not be taken together. It is preferable
to take mycophenolate mofetil on an empty stomach;
however, like azathioprine, it can be taken with food
because it, too, can cause stomach problems, such as
heartburn and nausea. Like azathioprine, mycophenolate mofetil is not a stand-alone drug; instead, it must be
used, in combination with other medications. This is
also the case with regard to sirolimus.
Physicians prescribe either mycophenolate mofetil
or azathioprine (in combination with other immunosuppressant drugs) to help patients cope with acute
bouts of organ rejection. The medications work by
interfering with the multiplication process of white
blood cells, which is part of the body’s natural defense
GALE ENCYCLOPEDIA OF MEDICINE

OKT3 prevents is prescribed to prevent organ rejection immediately after surgery and is also used to treat
acute rejection episodes; ATGAM and Thymoglobulin,
which are similar to OKT3, are used for the same reasons. All three drugs are given intravenously.
Tacrolimus, which is also known as FK506, is a
fairly new drug that is considered by many experts to
be as effective as cyclosporine. An alternative drug
choice for patients that cannot tolerate cyclosporine,
tacrolimus has been the subject of much research in
recent years. Used to treat rejection episodes that are
acute or chronic in nature, tacrolimus is being studied
to see if using it will allow patients to reduce their
dosage of prednisone without organ rejection.
In a presentation at the 2003 American
Transplant Congress, surgeons from the University
of Pittsburgh reported that an innovative clinical protocol developed by Dr. Thomas E. Starzl was implemented, which reduced the dosage of tacrolimus
needed by lung transplant patients with excellent success. Patients required lower doses of prednisone as
well. In fact, in some cases, patients were taking tacrolimus only once a day (rather than twice a day) or only
four times a week. Over the long-term, physicians
hope that there will be less risk of lung recipients
developing the kinds of complications normally associated with high levels of immunosuppressants, such
as kidney dysfunction, which is a common problem
faced by lung transplant patients.
Dr. Thomas E. Strazl, the renowned physician
often referred to as the modern-day father of transplantation, developed the protocol based on the knowledge
that some of his patients had stopped taking their daily
pills with no ill effects. Starzl theorized that giving several drugs to a patient immediately after surgery, which
was the normal practice, might inhibit the immune system from developing a tolerance for the new organ.
Therefore, his new protocol embraced a different
approach. Shortly before the transplantation, patients
were given a drug that killed their T-cells and after the
GALE ENCYCLOPEDIA OF MEDICINE

operation, patients received only one anti-rejection
medicine rather than the multi-pill cocktail normally
prescribed. In an article published by Lancet in 2003,
Starzl and colleagues reported the results of their pilot
study involving 82 two kidney, liver, pancreas or small
bowel transplant patients treated according to the new
drug protocol. Out of the 72 patients with successful
transplants after one year, over half the patients were
taking anti-rejection medication either every other day,
three times per week or twice per week. Amazingly, 11 of
the patients were taking only one pill a week and they
exhibited no signs of organ rejection or complications.
Certainly more research needs to be conducted, but
these results are very promising.

Recommended dosage
The dosages vary depending on the drug or drug
combination being taken by the patient. In general,
cyclosporine is taken every 12 hours in liquid or capsule
form. Tacrolimus is generally taken every 12 hours as
well. The level of either drug in a patient’s blood is
monitored carefully and doses are adjusted accordingly
in order to not only prevent reject, but also unpleasant
side effects. Azathioprine is taken once a day in tablet
form, whereas mycophenolate mofetil is generally taken
every 12 hours. High doses of prednisone are usually
given at first and then tapered down slowly.

Precautions
Patients should discuss proper storage methods
with regard to their medications. Sirolimus, for example, should be stored at room temperature with special
care taken to keep it out of excessive heat and humidity.
Although pregnant women taking anti-rejection
drugs have delivered healthy babies, women planning
on becoming pregnant while taking anti-rejection
drugs should talk with their physicians regarding any
possible complications. For example, the safety of
taking mycophenolate mofetil during pregnancy or
while breastfeeding is questionable and not advised.

Side effects
Side effects vary depending on the individual and
the drug therapy chosen. Patients should talk with
their doctors regarding the various side effects they
can expect and under what conditions emergency
medical care needs to be sought.

Interactions
It is essential that patients talk with their pharmacist and transplant team before taking any medications,
341

Anti-rejection drugs

system when foreign invaders, such as a new organ, are
detected. However, researchers at Duke University
and the University of Florida found that mycophenolate mofetil doesn’t work any better than azathioprine,
but costs significantly more. Aside from cost, another
consideration also needs to be the type of organ transplanted, because acute rejection rates differ. For
example, six months after surgery, approximately
15% of kidney recipients will have an acute rejection
episode as compared to approximately 60% of lung
recipients. And because study results vary depending
on the organ transplanted, more research is needed
with regard to the success of mycophenolate mofetil as
compared to azathioprine.

Antiretroviral drugs

regardless of whether they are prescription or over-thecounter drugs to ensure that the combinations will
not interact. For example, antacids can diminish the
effectiveness of mycophenolate mofetil and drugs used
to treat high cholesterol may increase the potency of
sirolimus. In addition, certain food products can also
alter the potency of some anti-rejection drugs. For
example, grapefruit and grapefruit juice can cause
cyclosporine blood levels to increase.
Resources
PERIODICALS

Mazariegos, G. V., Zahorchak, A. F., Reyes, J., et al.
‘‘Dendritic cell subset ratio in peripheral blood
correlates with successful withdrawal of
immunosuppression in liver transplant patients.’’
American Journal of Transplantation 3 (2003): 689–696.
Starzl, T. E., Murase, N., Abu-Elmagd, K., et al.
‘‘Tolerogenic immunosuppression for organ
transplantation.’’ Lancet 361 (2003): 1502–1510.
OTHER

Ross, Melanie Fridl ‘‘Duke/UF Researchers compare
anti-rejection medicines in lung transplant patients.’’
University of Florida 9 Aug 2001 University of Florida
News. 22 Feb 2005 <http://www.napa.ufl.edu/
2001news/antireject.htm>.
Rossi, Lisa ‘‘Studies of liver transplant patients off
anti-rejection drugs have altered cell profile.’’
University of Pittsburgh Medical Center 2 June 2003
University of Pittsburgh Medical Center. 22 Feb 2005
<http://www.eurekalert.org/pub_releases/2003-06/
uopm-so1060203.php>.
Srikameswaran, Anita ‘‘Protocol reduces transplant patients
need for anti-rejection drugs.’’ Post-Gazette.com Health
and Science 2 May 2003 PG Publishing Company, Inc.
22 Feb 2005 <http://www.post-gazette.com/
healthscience/20030502starzlhealth2p2.asp>.
University of Pittsburgh Medical Center ‘‘Our Experts:
Thomas E. Starzl, M.D., Ph.D.’’ University of
Pittsburgh Medical Center 2005 University of
Pittsburgh Medical Center. 22 Feb 2005 <http://
newsbureau.upmc.com/Bios/BioStarzl.htm>.

Lee Ann Paradise

I Antiretroviral drugs
Definition
Antiretroviral drugs inhibit the reproduction of
retroviruses—viruses composed of RNA rather than
DNA. The best known of this group is HIV, human
immunodeficiency virus, the causative agent of AIDS.
342

Purpose
Antiretroviral agents are virustatic agents which
block steps in the replication of the virus. The drugs
are not curative; however continued use of drugs,
particularly in multi-drug regimens, significantly
slows disease progression.

Description
There are three main types of antiretroviral drugs,
although only two steps in the viral replication process
are blocked. Nucleoside analogs, or nucleoside reverse
transcriptase inhibitors (NRTIs), such as didanosine
(ddI, Videx), lamivudine (3TC, Epivir), stavudine
(d4T, Zerit), zalcitabine (ddC, Hivid), and zidovudine
(AZT, Retrovir), act by inhibiting the enzyme reverse
transcriptase. Because a retrovirus is composed of
RNA, the virus must make a DNA strand in order to
replicate itself. Reverse transcriptase is an enzyme that
is essential to making the DNA copy. The nucleoside
reverse transcriptase inhibitors are incorporated into
the DNA strand. This is a faulty DNA molecule that is
incapable of reproducing.
The non-nucleoside reverse transcriptase inhibitors
(NNRTIs), such as delavirdine (Rescriptor), loviride,
and nevirapine (Viramune) act by binding directly to
the reverse transcriptase molecule, inhibiting its
activity.
A fourth class of drugs was under clinical trials in
2003. Called fusion inhibitors, they block HIV from
fusing with healthy cells. The first to receive FDA
approval will likely be a drug called Enfurvitide.
Because HIV mutates readily, the virus can
develop resistance to single drug therapy. However,
treatment with drug combinations appears to produce
a durable response. Proper treatment appears to
slow the progression of HIV infections and reduce
the frequency of opportunistic infections. One of the
most notable advances in recent years has been the
success of highly active antiretroviral therapy
(HAART). This multidrug approach reduced the
risk of opportunistic infections in persons with HIV/
AIDS and slowed the progression of the disease and
death. Usually, patients receive triple combination
therapy, however research in 2003 showed a new
once-daily regimen of quadruple therapy effective.
The combination included adefovir, lamivudine,
didanosine, and efavirenz. In short, the scientific community continues to make rapid advancements in
developing and evaluating antiretroviral drug therapy.
It is best to keep well informed and frequently check
with a physician.
GALE ENCYCLOPEDIA OF MEDICINE

Antiviral drugs—Medicines that cure or control
virus infections.
Bioavailability—A measure of the amount of drug
that is actually absorbed from a given dose.
Hypoxemia—Lower than normal oxygenation of
arterial blood.
Immune system—The body’s natural defenses
against disease and infection.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Pancreas—A gland located beneath the stomach.
The pancreas produces juices that help break down
food and secretes insulin that helps the body use
sugar for energy.
Insomnia—A sleep disorder characterized by
inability to either fall asleep or to stay asleep.
Mutates—Undergoes a spontaneous change in the
make-up of genes or chromosomes.
Pregnancy category— A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B:
Animal studies indicate no fetal risk, but no
human studies; or adverse effects in animals, but
not in well-controlled human studies. Category C:
No adequate human or animal studies; or adverse
fetal effects in animal studies, but no available
human data. Category D: Evidence of fetal risk,
but benefits outweigh risks. Category X: Evidence
of fetal risk. Risks outweigh any benefits.
Retrovirus—A virus composed of ribonucleic acid
(RNA) instead of deoxynucleic acid (DNA).
Virus—A tiny, disease-causing particle that can
reproduce only in living cells.

Recommended dosage
Doses must be individualized based on the patient
and use of interacting drugs. The optimum combinations of antiretroviral drugs have not been determined,
nor is there agreement on the stage of infection at
which to start treatment. In fact, starting treatment
too early has led to unwanted side effects in some
patients or problems with patient readiness to comply.
Treatment should begin when the time and circumstances are right.
GALE ENCYCLOPEDIA OF MEDICINE

Although the antiretroviral drugs fall into several
groups, each drug has a unique pattern of adverse
effects and drug interactions. Since the drugs are used
in various combinations, the frequency and severity
of adverse effects will vary with the combination.
Although most drug combinations show a higher
rate of adverse events than single drug therapy,
some patterns are not predictable. For example, indinavir has been reported to cause insomnia in 3% of
patients, however, when used in combination with
zidovudine, only 1.5% of patients complained of
sleep difficulties.
The most severe adverse effects associated with
the protease inhibitors are kidney and liver toxicity.
Patients also have reported a syndrome of abdominal
distention (selling and expansion) and increased body
odor, which may be socially limiting. Hemophilic
patients have reported increased bleeding tendencies
while taking protease inhibitors. The drugs are pregnancy category B. There have been no controlled studies of safety in pregnancy. HIV-infected mothers are
advised not to breast feed in order to prevent transmission of the virus to the newborn.
The nucleoside reverse transcriptase inhibitors
have significant levels of toxicity. Lactic acidosis in
the absence of hypoxemia and severe liver enlargement
with fatty degeneration have been reported with zidovudine and zalcitabine, and are potentially fatal. Rare
cases of liver failure, considered possibly related to
underlying hepatitis B and zalcitabine monotherapy,
have been reported.
Abacavir has been associated with fatal hypersensitivity reactions. Didanosine has been associated
with severe pancreatitis. Nucleoside reverse transcriptase inhibitors are pregnancy category C.
There is limited information regarding safety during
pregnancy. Zidovudine has been used during pregnancy to reduce the risk of HIV infection to the
infant. HIV-infected mothers are advised not to
breast feed in order to prevent transmission of the
virus to the newborn.
Efavirenz has been associated with a high frequency of skin rash, 27% in adults and 40% in children. Nevirapine has been associated with severe liver
damage and skin reactions. All of the non-nucleoside
reverse transcriptase inhibitors are pregnancy category C, based on animal studies.
Using antiretroviral drugs in combination also
helps lower risk of developing viral resistance. Fifty
percent of patients who fail antiretroviral therapy are
343

Antiretroviral drugs

Precautions

KEY TERMS

Antirheumatic drugs

resistant to one class of drug. Recent research into
multiple drugs and combinations is promising.

Interactions

Health Services Administration. (800) HIV-0440 (800)
448-0440. <http://www.hivatis.org>.
Project Inform National HIV/AIDS Treatment Hotline.
(800) 822-7422.

Because of the high frequency of drug interactions
associated with AIDS therapy, specialized references
should be consulted. Use of recreational drugs while
on antriretroviral therapy can trigger potentially lethal
side effects or negate the positive effects of the therapy.
Saquinavir is marketed in both hard and soft
gelatin capsules. Because saquinavir in the hard gelatin capsule formulation (Invirase) has poor bioavailability, it is recommended that this formulation only
be used in combination with other drugs which interact to raise saquinavir blood levels. Saquinavir soft
gelatin capsules (Fortovase) are the preferred dosage
form of this drug.

Samuel D. Uretsky, PharmD
Teresa G. Odle

I Antirheumatic drugs
Definition
Antirheumatic drugs are drugs used to treat rheumatoid arthritis.

Purpose
Resources
PERIODICALS

‘‘Grant Awarded for Evaluation of Once-Daily
Antiretroviral.’’ Virus Weekly (November 26, 2002): 12.
Isaac, A., and D. Pillay. ‘‘New Drugs for Treating Drug
Resistant HIV–1: Clinical Management of Virological
Failure Remains an Important and Difficult Issue for
HIV Physicians.’’ Sexualy Transmitted Diseases (June
2003): 176–183.
‘‘New Therapy Strategies Focusing on Long Term: DrugsÆ
Impact on Heart is Debated.’’ AIDS Alert April 2003: 45.
‘‘Once-Daily Quadruple Regimen Safe, Effective.’’ AIDS
Weekly (October 7, 2003): 4.
‘‘Recreational Drugs can Reduce Safety, Efficacy of
Antiretroviral Agents.’’ AIDS Weekly (December 16,
2003): 3.
Thanker, H.K., and M.H. Snow. ‘‘HIV Viral Suppression in
the Era of Antiretroviral Therapy.’’ Postgraduate
Medical Journal (January 2003): 36.

Rheumatoid arthritis is a progressive form of
arthritis that has devastating effects on joints and
general health. It is classified as an auto-immune disease, because the disease is caused by the body’s own
immune system acting against the body itself.
Symptoms include painful, stiff, swollen joints, fever,
fatigue, and loss of appetite.
In recent years, there has been a change in attitude
concerning the treatment of rheumatoid arthritis.
Physicians now use Disease Modifying Anti-Rheumatic
Drugs (DMARDs) early in the history of the disease and
are less inclined to wait for crippling stages before resorting to the more potent drugs. Fuller understanding of the
side-effects of non-steroidal anti-inflammatory drugs
(NSAIDs) has also stimulated reliance on other types
of antirheumatic drugs.

Description

ORGANIZATIONS

Project Inform. 205 13th Street, #2001, San Francisco, CA
94103. (415) 558-8669. <http://www.projinf.org>.

The major classes of antirheumatic drugs include:


Nonsteroidal Anti-Inflammatory Drugs (NSAIDs.
Drugs belonging to this class bring symptomatic
relief of both inflammation and pain, but have a
limited effect on the progressive bone and cartilage
loss associated with rheumatoid arthritis. They act
by slowing the body’s production of prostaglandins.
Common NSAIDs include: ibuprofen (Motrin,
Nuprin or Advil), naproxen (Naprosyn, Aleve) and
indomethacin (Indocin).



Corticosteroids. These drugs are very powerful antiinflammatory agents. They are the synthetic analogs
of cortisone, produced by the body. Corticosteroids
are used to reduce inflammation and suppress

OTHER

AIDS Clinical Trials Information Service website and telephone information line. Sponsored by Centers for
Disease Control and Prevention, Food and Drug
Administration, National Institute of Allergy and
Infectious Diseases, and National Library of Medicine.
(800) TRIALS-A or (800) 874-2572. <http://actis.org>.
HIV/AIDS Treatment Information Service website and
telephone information line. Sponsored by Agency for
Health Care Policy and Research, Centers for Disease
Control and Prevention, Health Resources and Services
Administration, Indian Health Service, National
Institutes of Health, and Substance Abuse and Mental
344

GALE ENCYCLOPEDIA OF MEDICINE

Anti-inflammatory drugs—A class of drugs that
lower inflammation and that includes NSAIDs and
corticosteroids.
Arthritis—A painful condition that involves inflammation of one or more joints.

the production of antibodies to fight off specific foreign substances or agents (antigens).
Immune system—The sum of the defence mechanisms of the body that protects it against foreign substances and organisms causing infection.

Conception—The union of egg and sperm to form a
fetus.
Corticosteroids—A class of drugs that are synthetic
versions of the cortisone produced by the body. They
rank among the most powerful anti-inflammatory
agents.
Cortisone—Glucocorticoid produced by the adrenal
cortex in response to stress. Cortisone is a steroid and
has anti-inflammatory and immunosuppressive
properties.

Immunosuppressive—Any agent that suppresses the
immune response of an individual.

Cytotoxic drugs—Drugs that function by destroying
cells.
Disease
Modifying
Anti-Rheumatic
Drugs
(DMARDs)—A class of antirheumatic drugs, including chloroquine, methotrexate, cyclosporine, and
gold compounds, that influence the disease process
itself and do not only treat its symptoms.
Inflammation—A process occurring in body tissues,
characterized by increased circulation and the accumulation of white blood cells. Inflammation also occurs
in disorders such as arthritis and causes harmful effects.
Inflammatory—Pertaining to inflammation.

Non steroidal—Not containing steroids or cortisone.
Usually refers to a class of drugs called Non Steroidal
Anti-Inflammatory Drugs (NSAID).

Immune response—Physiological response of the
body controlled by the immune system that involves

activity of the immune system. The most commonly
prescribed are prednisone and dexamethasone.


Disease
Modifying
Anti-Rheumatic
Drugs
(DMARDs). DMARDs influence the disease process
itself and do not only treat symptoms, hence their
name. DMARDs also have anti-inflammatory effects,
and most were borrowed from the treatment of other
diseases, such as cancer and malaria. Antimalarials
DMARDs include chloroquine (Aralen) and hydroxychloroquine (Plaquenil). Powerful DMARDs include:
methotrexate (Rheumatrex), sulfasalazine, cyclosporine, azathioprine (Imuran) and cyclophosphamide
(Cytoxan), azathioprine, sulfasalazine, penicillamine,
and organic gold compounds such as aurothioglucose
(Solganol), gold sodium thiomalate (Aurolate) and
auranofin (Ridaura).

GALE ENCYCLOPEDIA OF MEDICINE

Immunosuppresive cytotoxic drugs—A class of
drugs that function by destroying cells and suppressing the immune response.
Methotrexate—A drug that interferes with cell
growth and is used to treat rheumatoid arthritis as
well as various types of cancer. Side-effects may
include mouth sores, digestive upsets, skin rashes,
and hair loss.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)—
A class of drugs that is used to relieve pain, and
symptoms of inflammation, such as ibuprofen and
ketoprofen.
Osteoarthritis—A form of arthritis that occurs
mainly in older people and involves the gradual
degeneration of the cartilage of the joints.
Prostaglandins—Prostaglandins are produced by
the body and are responsible for inflammation
features, such as swelling, pain, stiffness, redness
and warmth.



Slow-Acting Antirheumatic Drugs (SAARDs).
SAARDs are a special class of DMARDs and the
effect of these drugs is slow acting and not so quickly
apparent as that of the NSAIDs. Examples are
hydroxychloroquine and aurothioglucose.



Immunosuppresive cytotoxic drugs. This class of
drugs is used if treatment with NSAIDs and
SAARDs have no effect. Immunosuppresive drugs
have a stabilizing effect on the immune system.
Since the inflammation associated with chronic
arthritis is due to malfunctions of the immune
system, use of this class of drugs has been shown
to be beneficial for the treatment of rheumatoid
arthritis as well. Examples are: methotrexate,
mechlorethamine, cyclophosphamide, chlorambucil, and azathioprine.
345

Antirheumatic drugs

KEY TERMS

Antiseptics

Recommended dosage
Recommended dosage depends on the type of
drug. The prescribing physician or the pharmacist
provide information for the correct dosage. The
drugs must be taken exactly as directed.
When taking methotrexate for rheumatoid arthritis, it should be taken only once or twice a week as
prescribed, not every day. Taking it every day can lead
to a fatal overdose.

Precautions
Many antirheumatic drugs such as, for example,
azathioprine
(Imuran)
and
methotrexate
(Rheumatrex), are very powerful drugs. They are
usually prescribed in severe cases, when all other treatments have failed. Thus, they may have serious side
effects, so it is important to be monitored closely by a
physician while taking any of these drugs.

certain whether these reactions were caused by entanercept, but multiple sclerosis has been seen in patients taking other drugs which act against tumor necrosis factor.

Interactions
Antirheumatic drugs may interact with a variety of
other medicines or other antirheumatic drugs. When this
happens, the effects of one or both of the drugs may
change, or the risk of side effects may be greater. Anyone
who takes this type of drug should inform the prescribing
physician about any other medication he or she is taking.
Among the drugs that may interact with antirheumatic
drugs are phenytoin (Dilantin), aspirin, sulfa drugs such
as Bactrim and Gantrisin, tetracycline and some other
antibiotics and cimetidine (Tagamet). NSAIDs such as
ibuprofen (Motrin, Advil) are also known to interact
with other classes of antirheumatic drugs.
Nancy Ross-Flanigan

Side effects
Hydroxychloroquine (Plaquenil) may cause vision
problems. Anyone taking it should see an ophthalmologist (a physician who specializes in treating eyes) for a
thorough eye examination every six months.
Methotrexate and penicillamine may cause birth
defects. Women taking these drugs must stop taking
them during pregnancy and for several months before
a planned pregnancy. Methotrexate may also cause
lung damage or fertility problems and should not be
taken by anyone with serious kidney or liver disease or
by anyone who drinks alcohol.
Azathioprine may cause birth defects if either the
man or woman is using it at the time of conception.
Anyone who uses this drug and is sexually active
should consult with a physician about an effective
birth control method.
Other common side effects of antirheumatic drugs
include abdominal cramps, diarrhea, dizziness, loss of
appetite, headache, nausea, vomiting, fever and chills,
and mouth sores. A variety of other side effects may
occur. Anyone who has unusual symptoms while taking
antirheumatic drugs should notify the treating physician.
The gold compounds may cause serious blood
problems by reducing the ability of the blood forming
organs to produce blood cells. These drugs may
decrease the number of white blood cells, red blood
cells, or both. Patients taking these drugs should have
regular blood counts.
Entanercept (Enbrel) may also cause blood problems, and some patients who received this drug have
developed eye problems and multiple sclerosis. It is not
346

I Antiseptics
Definition
An antiseptic is a substance which inhibits the
growth and development of microorganisms. For
practical purposes, antiseptics are routinely thought
of as topical agents, for application to skin, mucous
membranes, and inanimate objects, although a formal
definition includes agents which are used internally,
such as the urinary tract antiseptics.

Purpose
Antiseptics are a diverse class of drugs which are
applied to skin surfaces or mucous membranes for
their anti-infective effects. This may be either bacteriocidal or bacteriostatic. Their uses include cleansing
of skin and wound surfaces after injury, preparation of
skin surfaces prior to injections or surgical procedures,
and routine disinfection of the oral cavity as part of a
program of oral hygiene. Antiseptics are also used for
disinfection of inanimate objects, including instruments and furniture surfaces.
Commonly used antiseptics for skin cleaning
include benzalkonium chloride, chlorhexidine, hexachlorophine, iodine compounds, mercury compounds,
alcohol and hydrogen peroxide. Other agents which
have been used for this purpose, but have largely been
supplanted by more effective or safer agents, include
GALE ENCYCLOPEDIA OF MEDICINE

Antibiotic—A medicine used to treat infections.
Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Mucous membrane—The moist lining of a body
cavity or structure, such as the mouth or nose.
Residue—Traces that remain after most of the rest
of the material is gone.

Dosage varies with product and intended use.
Consult individualized references.

Precautions
Precautions vary with individual product and use.
Consult individualized references.
Hypersensitivity reactions should be considered
with organic compounds such as chlorhexidine, benzalkonium and hexachlorophine.

boric acid and volatile oils such as methyl salicylate
(oil of wintergreen.)

Skin dryness and irritation should be considered
with all products, but particularly with those containing alcohol.

Chlorhexidine shows a high margin of safety when
applied to mucous membranes, and has been used in
oral rinses and preoperative total body washes.

Systemic toxicity may result from ingestion of
iodine containing compounds or mercury compounds.

Benzalkonium chloride and hexachlorophine are
used primarily as hand scrubs or face washes.
Benzalkonium may also find application is a disinfecting agent for instruments, and in low concentration as
a preservative for drugs including ophthalmic solutions. Benzalkonium chloride is inactivated by organic
compounds, including soap, and must not be applied
to areas which have not been fully rinsed.
Iodine compounds include tincture of iodine and
povidone iodine compounds. Iodine compounds have
the broadest spectrum of all topical anti-infectives, with
action against bacteria, fungi, viruses, spores, protozoa,
and yeasts. Iodine tincture is highly effective, but its
alcoholic component is drying and extremely irritating
when applied to abraided (scraped or rubbed) skin.
Povidone iodine, an organic compound, is less irritating
and less toxic, but not as effective. Povidone iodine has
been used for hand scrubs and disinfection of surgical
sites. Aqueous solutions of iodine have also been used
as antiseptic agents, but are less effective than alcoholic
solutions and less convenient to use that the povidone
iodine compounds.
Hydrogen peroxide acts through the liberation of
oxygen gas. Although the antibacterial activity of hydrogen peroxide is relatively weak, the liberation of oxygen
bubbles produces an effervescent action, which may be
useful for wound cleansing through removal of tissue
debris. The activity of hydrogen peroxide may be
reduced by the presence of blood and pus. The appropriate concentration of hydrogen peroxide for antiseptic
use is 3%, although higher concentrations are available.
Thimerosol (Mersol) is a mercury compound with
activity against bacteria and yeasts. Prolonged use
may result in mercury toxicity.
GALE ENCYCLOPEDIA OF MEDICINE

Chlorhexidine should not be instilled into the ear.
There is one anecdotal report of deafness following
use of chlorhexidine in a patient with a perforated
eardrum. Safety in pregnancy and breastfeeding have
not been reported, however there is one anecdotal
report of an infant developing slowed heartbeat
apparently related to maternal use of chlorhexidine.
Iodine compounds should be used sparingly
during pregnancy and lactation due to risk of infant
absorption of iodine with alterations in thyroid function.

Interactions
Antiseptics are not known to interact with any
other medicines. However, they should not be used
together with any other topical cream, solution, or
ointment.
Resources
PERIODICALS

Farley, Dixie. ‘‘Help for Cuts, Scrapes and Burns.’’ FDA
Consumer May 1996: 12.

Samuel D. Uretsky, PharmD

I Antispasmodic drugs
Definition
Antispasmodic drugs relieve cramps or spasms of
the stomach, intestines, and bladder.
347

Antispasmodic drugs

Recommended dosage

KEY TERMS

Antispasmodic drugs

KEY TERMS
Heat stroke—A serious condition that results from
exposure to extreme heat. The body loses its ability
to cool itself. Severe headache, high fever, and hot,
dry skin may result. In severe cases, a person with
heat stroke may collapse or go into a coma.
Hiatal hernia—A condition in which part of the
stomach protrudes through the diaphragm.
Hyperthyroidism—Secretion of excess thyroid hormones by the thyroid gland.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Myasthenia gravis—A condition in which certain
muscles weaken and may become paralyzed.
Reflux esophagitis—Inflammation of the lower
esophagus caused by the backflow of stomach
contents.
Spasm—Sudden, involuntary tensing of a muscle or
a group of muscles
Ulcerative colitis—Long-lasting and repeated
inflammation of the colon with the development
of sores.

Purpose
Antispasmodic drugs have been used to treat
stomach cramps. Traditionally, they were used to
treat stomach ulcers, but for this purpose they have
largely been replaced by the acid inhibiting
compoundsa, the H-2 receptor blockers such as
cimetidine and ranitidine and the proton pump
inhibtors such as omeprazole, lansoprazole and
rabetazole.
Most of the drugs used for this purpose as ‘‘anticholinergics’’, since they counteract the effects of the
neurohormone acetylcholine. Some of these drugs are
derived from the plant belladonna, also known as
Deadly Nightshade. There is also a group of drugs
with similar activity, but not taken from plant sources.
The anticholingergics decrease both the movements of
the stomach and intestine, and also the secretions of
stomach acid and digestive enzymes. They may be
used for other purposes including treatment of
Parkinson’s Disease, and bladder urgency. Because
these drugs inhibit secretions, they cause dry mouth
and dry eyes because of reduced salivation and tearing. Dicyclomine is an antispasmodic with very lettle
348

effect on secretions. It is used to treat irritable bowel
syndrome.

Description
Dicyclomine is available only with a prescription
and is sold as capsules, tablets (regular and extendedrelease forms), and syrup.

Recommended dosage
The usual dosage for adults is 20 mg, four times a
day. However, the physician may recommend starting
at a lower dosage and gradually increasing the dose to
reduce the chance of unwanted side effects.
The dosage for children depends on the child’s
age. Check with the child’s physician for the correct
dosage.

Precautions
Dicyclomine makes some people sweat less,
which allows the body to overheat and may lead to
heat prostration (fever and heat stroke). Anyone
taking this drug should try to avoid extreme heat.
If that is not possible, check with the physician
who prescribed the drug. If heat prostration occurs,
stop taking the medicine and call a physician
immediately.
This medicine can cause drowsiness and blurred
or double vision. People who take this drug should not
drive, use machines, or do anything else that might be
dangerous until they have found out how the medicine
affects them.
Dicyclomine should not be given to infants or
children unless the physician decides the use of this
drug is necessary. Diclyclomine should not be used by
women who are breast feeding. Women who are pregnant or plan to become pregnant should check with
their physicians before using this drug.
Anyone with the following medical conditions
should not take dicyclomine unless directed to do so
by a physician:


Previous sensitivity
dicyclomine

or

allergic

reaction

to



Glaucoma



Myasthenia gravis



Blockage of the urinary tract, stomach, or intestines



Severe ulcerative colitis



Reflux esophagitis.
GALE ENCYCLOPEDIA OF MEDICINE



Liver disease



Kidney disease



High blood pressure



Heart problems



Enlarged prostate gland



Hiatal hernia



Autonomic neuropathy (a nerve disorder)



Hyperthyroidism.

I Antituberculosis drugs
Definition
Antituberculosis drugs are medicines used to treat
tuberculosis, an infectious disease that can affect the
lungs and other organs.

Purpose

Side effects
The most common side effects are dizziness, drowsiness, lightheadedness, nausea, nervousness, blurred
vision, dry mouth, and weakness. Other side effects
may occur. Anyone who has unusual symptoms after
taking dicyclomine should get in touch with his or her
physician.

Interactions
Dicyclomine may interact with other medicines.
When this happens, the effects of one or both of the
drugs may change or the risk of side effects may be
greater. Among the drugs that may interact with
Dicyclomine are:


Antacids such as Maalox



Antihistamines such as clemastine fumarate (Tavist)



Bronchodilators (airway opening drugs) such as
albuterol (Proventil, Ventolin)



Corticosteroids such as prednisone (Deltasone)



Monoamine oxidase inhibitors (MAO inhibitors) such
as phenelzine (Nardil) and tranylcypromine (Parnate)



Tranquilizers such as diazepam (Valium) and alprazolam (Xanax).

The list above does not include every drug that
may interact with dicyclomine. Be sure to check with a
physician or pharmacist before combining dicyclomine with any other prescription or nonprescription
(over-the-counter) medicine.
Nancy Ross-Flanigan

Antistreptolysin O titer (ASO) see
Streptococcal antibody tests
Antithrombin III deficiency see
Hypercoagulation disorders
GALE ENCYCLOPEDIA OF MEDICINE

Tuberculosis is a disease caused by Mycobacterium
tuberculae, a bacteria that is passed between people
through the air. The disease can be cured with proper
drug therapy, but because the bacteria may become
resistant to any single drug, combinations of antituberculosis drugs are used to treat tuberculosis (TB) are
normally required for effective treatment. At the start
of the 20th Century, tuberculosis was the most common
cause of death in the United States, but was laregly
eliminated with better living conditions. It is most common in areas of crowding and poor ventilation, suich as
crowded urban areas and prisons. In some areas, the
AIDS epidemic has been accompanied by an increase
in the prevalence of tuberculosis.
Some antituberculosis drugs also are used to treat
or prevent other infections such as Mycobacterium
avium complex (MAC), which causes disease throughout the bodies of people with AIDS or other diseases
of the immune system.

Description
Antituberculosis drugs are available only with a
physician’s prescription and come in tablet, capsule,
liquid and injectable forms. Some commonly used
antituberculosis drugs are cycloserine (Seromycin),
ethambutol (Myambutol), ethionamide (TrecatorSC), isoniazid (Nydrazid, Laniazid), pyrazinamide,
rifabutin (Mycobutin), and rifampin (Rifadin,
Rimactane).

Recommended dosage
The recommended dosage depends on the type of
antituberculosis drug and may be different for different patients. Check with the physician who prescribed
the medicine or the pharmacist who filled the prescription for the proper dosage. The physician may gradually increase the dosage during treatment. Be sure to
follow the physician’s orders. Patients who are infected
with HIV must usually take larger combinations of
drugs for a longer period of time than is needed for
patients with an unimpaired immune system.
349

Antituberculosis drugs

In addition, patients with these conditions should
check with their physicians before using dicyclomine:

Antituberculosis drugs

KEY TERMS
Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Feces—(Also called stool.) The solid waste that is
left after food is digested. Feces form in the intestines and pass out of the body through the anus.
Fetus—A developing baby inside the womb.
Gout—A disease in which uric acid, a waste product that normally passes out of the body in urine,
collects in the joints and the kidneys. This causes
arthritis and kidney stones.
Immune system—The body’s natural defenses
against disease and infection.
Microorganism—An organism (life form) that is too
small to be seen with the naked eye.
Platelets—Disk-shaped bodies in the blood that are
important in clotting.
Seizure—A sudden attack, spasm, or convulsion.

Some antituberculosis drugs must be taken with
other drugs. If they are taken alone, they may encourage the bacteria that cause tuberculosis to become
resistant to drugs used to treat the disease. When the
bacteria become resistant, treating the disease
becomes more difficult.

remember to take the medicine during the day, check
with a health care professional for suggestions.
Do not take antacids that contain aluminum, such
as Maalox, within 1 hour of taking isoniazid, as this
may keep the medicine from working.

Precautions
Seeing a physician regularly while taking antituberculosis drugs is important. The physician will check
to make sure the medicine is working as it should and
will watch for unwanted side effects. These visits also
will help the physician know if the dosage needs to be
changed.
Symptoms should begin to improve within a few
weeks after treatment begins with antituberculosis
drugs. If they do not, or if they become worse, check
with a physician.
Some people feel drowsy, dizzy, confused, or less
alert when using these drugs. Some may also cause
vision changes, clumsiness, or unsteadiness. Because
of these possible problems, anyone who takes antituberculosis drugs should not drive, use machines, or do
anything else that might be dangerous until they have
found out how the medicine affects them.
Daily doses of pyridoxine (vitamin B6) may lessen
or prevent some side effects of ethionamide or isoniazid.
If the physician who prescribed the medicine recommends this, be sure to take the pyridoxine every day.

To clear up tuberculosis completely, antituberculosis drugs must be taken for as long as directed. This
may mean taking the medicine every day for a year or
two or even longer. Symptoms may improve very
quickly after treatment with this medicine begins.
However, they may come back if the medicine is
stopped too quickly. Do not stop taking the medicine
just because symptoms improve.

Certain kinds of cheese (such as Swiss and
Cheshire) and fish (such as tuna and skipjack) may
cause an unusual reaction in people taking isoniazid.
Symptoms of this reaction include fast or pounding
heartbeat, sweating or a hot feeling, chills or a clammy
feeling, headache, lightheadedness, and red or itchy skin.
This reaction is very rare. However, if any of these symptoms occur, check with a physician as soon as possible.

Because people may neglect to take their medication for tuberculosis, it is common to have tuberculosis centers develop a program of Directly Observed
Therapy (DOT.) In these programs, patients come to
the hospital or clinic, and take their medication in
front of an observer. These programs may be annoying to the patients, but are justified by the risks to
public health if tuberculosis germs which have become
resistant to drugs were to be spread.

Rifabutin and rifampin will make saliva, sweat,
tears, urine, feces, and skin turn reddish orange to
reddish brown. This is nothing to worry about.
However, the discolored tears may permanently stain
soft contact lenses (but not hard contact lenses). To
avoid ruining contact lenses, do not wear soft contacts
while taking these medicines.

Cycloserine works best when it is at constant
levels in the blood. To help keep levels constant, take
the medicine in doses spaced evenly through the day
and night. Do not miss any doses. If taking medicine at
night interferes with sleep, or if it is difficult to
350

Rifampin may temporarily lower the number of
white blood cells. Because the white blood cells are
important in fighting infection, this effect increases the
chance of getting an infection. This drug also may
lower the number of platelets that play an important
role in clotting. To reduce the risk of bleeding and
infection in the mouth while taking this medicine, be
GALE ENCYCLOPEDIA OF MEDICINE

Rifampin may affect the results of some medical
tests. Before having medical tests, anyone taking this
medicine should alert the health care professional in
charge.
People who have certain medical conditions may
have problems if they take antituberculosis drugs. For
example:




Anyone who has had unusual reactions to antituberculosis drugs or to niacin should let his or her
physician know before taking any antituberculosis
drug. The physician should also be told about any
allergies to foods, dyes, preservatives, or other
substances.
Patients who are on special diets, such as lowsodium or low-sugar diets, should make sure their
physicians know. Some antituberculosis medicines
may contain sodium, sugar, or alcohol.

cycloserine or isoniazid may increase the risk of seizures (convulsions) in people with a history of
seizures.
the dosage of cycloserine may need to be adjusted for
people with kidney disease.



ethambutol or pyrazinamide may cause or worsen
attacks of gout in people who are prone to having
them.



ethambutol may cause or worsen eye damage.



diabetes may be harder to control in patients who
take ethionamide.



isoniazid may cause false results on some urine sugar
tests, and pyrazinamide may cause false results on
urine ketone tests. Diabetic patients who either of
these medicines should discuss the possibility of false
test results with their physicians.



medicine and are worried about birth defects or other
problems should talk to their physicians.

people with liver disease or a history of alcohol
abuse may be more likely to develop hepatitis
when taking isoniazid and are more likely to have
side effects that affect the liver when taking
rifampin.



in people with kidney disease, ethambutol, ethionamide, or isoniazid may be more likely to cause side
effects.



side effects are also more likely in people with liver
disease who take pyrazinamide.

Before taking antituberculosis drugs, be sure to let
the physician know about these or any other medical
problems.
In laboratory tests of pregnant animals, high
doses of some antituberculosis drugs have caused
birth defects and other problems in the fetus or newborn. However, pregnant women with tuberculosis
need to take antituberculosis drugs to clear up their
disease. Knowing that many women have had healthy
babies after taking these drugs during pregnancy may
be reassuring. Pregnant women who need to take this
GALE ENCYCLOPEDIA OF MEDICINE

Side effects
Cycloserine
In some people, this medicine causes depression
and thoughts of suicide. If this happens, check with a
physician immediately. Switching to another medicine
will usually stop these troubling thoughts and feelings.
Also let the physician know immediately about any
other mood or mental changes; such as nervousness,
nightmares, anxiety, confusion, or irritability; and
about symptoms such as muscle twitches, convulsions,
or speech problems.
Headache is a common side effect that usually
goes away as the body adjusts to this medicine. This
problem does not need medical attention unless it
continues or it interferes with everyday life.

Ethambutol
This medicine may cause eye pain or vision
changes, including loss of vision or changes in color
vision. Check with a physician immediately if any of
these problems develop.
In addition, anyone who has any of these symptoms while taking ethambutol should check with a
physician immediately:


painful or swollen joints, especially in the knee,
ankle, or big toe



a tight, hot sensation in the skin over painful or
swollen joints



chills.

Other side effects may occur but do not need
medical attention unless they are bothersome or they
do not go away as the body adjusts to the medicine.
These include: headache, confusion, nausea and
vomiting, stomach pain, and loss of appetite.
351

Antituberculosis drugs

especially careful when brushing and flossing the
teeth. Check with a physician or dentist for suggestions on how to keep the teeth and mouth clean without causing injuries. Put off any dental work until
blood counts return to normal.

Antituberculosis drugs

Ethionamide
Check with a physician immediately if eye pain,
blurred vision, or other vision changes occur while
taking this medicine.
Symptoms such as unsteadiness, clumsiness and
pain, numbness, tingling, or burning in the hands or
feet could be the first signs of nerve problems that may
become more serious. If any of these symptoms occur,
check with a physician immediately. Other side effects
that should be brought to a physician’s attention
immediately include yellow eyes or skin and mood or
mental changes such as depression or confusion.
Less serious side effects such as dizziness, nausea
or vomiting, appetite loss, sore mouth, or metallic
taste may also occur. These problems usually go
away as the body adjusts to the medicine. They do
not need medical attention unless they continue or
they interfere with normal activities.
Isoniazid
This medicine may cause serious liver damage, especially in people over 40 years of age. However, taking
medicine for tuberculosis is very important for people
with the disease. Anyone who has tuberculosis and has
been advised to take this drug should thoroughly discuss
treatment options with his or her physician.
Recognizing the early signs of liver and nerve
damage can help prevent the problems from getting
worse. If any of these symptoms occur, check with a
physician immediately:


unusual tiredness or weakness



clumsiness or unsteadiness



pain, numbness, tingling, or burning in the hands
and feet



loss of appetite



vomiting

This medicine may also cause less serious side
effects such as diarrhea and stomach pain. These usually
go away as the body adjusts to the medicine and do not
need medical attention unless they continue.
If eye pain, blurred vision, or other vision changes
occur while taking this medicine, check with a physician immediately.
Pyrazinamide
Check with a physician immediately if pain in the
joints occurs.
352

Rifabutin
Check with a physician immediately if a skin rash
occurs.
Rifampin
Stop taking rifampin and check with a physician
immediately if any of the following symptoms occur.
These symptoms could be early signs of problems that
may become more serious. Getting prompt medical
attention could prevent them from getting worse.


unusual tiredness or weakness



nausea or vomiting



loss of appetite

In addition, anyone who has any of these symptoms while taking rifampin should check with a physician immediately:


breathing problems



fever



chills



shivering



headache



dizziness



itching



skin rash or redness



muscle and bone pain

Other side effects, such as diarrhea and stomach
pain, may occur with this medicine, but should go
away as the body adjusts to the drug. Medical treatment is not necessary unless these problems continue.
Other side effects may occur with any antituberculosis drug. Anyone who has unusual symptoms
while taking an antituberculosis drug should get in
touch with his or her physician.

Interactions
Taking cycloserine and ethionamide together may
increase the risk of seizures and other nervous system
problems. These and other side effects also are more
likely in people who drink alcohol while taking cycloserine. To avoid these problems, do not drink alcohol
while taking cycloserine and check with a physician
before combining cycloserine and ethionamide.
Drinking alcohol regularly may prevent isoniazid
from working properly and may increase the chance of
liver damage. Anyone taking this medicine should
strictly limit the use of alcohol. Check with a health
GALE ENCYCLOPEDIA OF MEDICINE

Many drugs may interact with isoniazid or rifampin,
increasing the chance of liver damage or other side effects.
Among these drugs are acetaminophen (Tylenol), birth
control pills and other drugs that contain female hormones, and the antiseizure drugs divalproex (Depakote)
and valproic acid (Depakene). For a complete list of
drugs that may have this effect, check with a pharmacist.
Isoniazid may also decrease the effects of the antifungal drug ketoconazole (Nizoral) and the antituberculosis drug rifampin (Rifadin).
Rifampin may make many drugs less effective.
Among the drugs that may be affected are diabetes
medicines taken by mouth (oral hypoglycemics), digitalis heart drugs, many antifungal drugs, and birth
control pills. Because it makes birth control pills less
effective, taking rifampin may increase the chance of
becoming pregnant. Women who take this medicine
along with birth control pills should use an additional
form of birth control. For a complete list of drugs that
may be affected by rifampin, check with a pharmacist.
Using rifabutin with the antiretroviral drug zidovudine (AZT, Retrovir) may make the zidovudine less
effective. Consult with a physician if both drugs are
prescribed.
Not every drug that may interact with an antituberculosis drug is listed here. Be sure to check with a
physician or pharmacist before combining an antituberculosis drug with any other prescription or nonprescription (over-the-counter) medicine.
Resources
PERIODICALS

Cornwall, Janet. ‘‘Tuberculosis: A Clinical Problem of
International Importance.’’ The Lancet (August 30,
1997): 660.

Nancy Ross-Flanigan

Antiulcer drugs

care professional for advice on the amount of alcohol
that may safely be used.

Antiulcer Drugs

Brand Name
(Generic Name)
Axid (nitzatidine)
Carafate (sucralfate)
Cytotec (misoprostol)

Pepcid (famotidine)
Prilosec (omeprazole)
Tagamet (cimetidine)
Zantac (ranitidine
hydrochloride)

Possible Common Side Effects Include:
Diarrhea, headache, nausea and vomiting, sore
throat
Constipation, insomnia, hives, upset stomach,
vomiting
Cramps, diarrhea, nausea, gas, headache,
menstrual disorders (including heavy bleeding
and severe cramping)
Constipation or diarrhea, dizziness, fatigue,
fever
Nausea and vomiting, headache, diarrhea,
abdominal pain
Headache, breast development in men, depression and disorientation
Headache, constipation or diarrhea, joint pain

Purpose
Recurrent gastric and duodenal ulcers are caused
by Helicobacter pylori infections, and are treated
with combination treatments that incorporate antibiotic therapy with gastric acid suppression.
Additionally, bismuth compounds have been used.
The primary class of drugs used for gastric acid
suppression are the proton pump inhibitors, omeprazole, lansoprazole, pantoprazole and rabeprazole. The
H-2 receptor blocking agents, cimetidine, famotidine,
nizatidine, and ranitidine have been used for this
purpose, but are now more widely used for maintenance therapy after treatment with the proton pump
inhibitors. Sucralfate, which acts by forming a protective coating over the ulcerate lesion, is also used in
ulcer treatment and may be appropriate for patients in
whom other classes of drugs are not indicated, or those
whose gastric ulcers are caused by non-steroidal antiinflammatory drugs (NSAIDs) rather than H. pylori
infections.

Description

I Antiulcer drugs
Definition
‘Antiulcer drugs are a class of drugs, exclusive of
the antibacterial agents, used to treat ulcers in the
stomach and the upper part of the small intestine.
GALE ENCYCLOPEDIA OF MEDICINE

The proton pump inhibitors block the secretion of
gastric acid by the gastric parietal cells. The extent of
inhibition of acid secretion is dose related. In some
cases, gastric acid secretion is completely blocked for
over 24 hours on a single dose. In addition to their role
in treatment of gastric ulcers, the proton pump inhibitors are used to treat syndromes of excessive acid
secretion (Zollinger-Ellison Syndrome) and gastroesophageal reflux disease (GERD).
353

Antiulcer drugs

KEY TERMS
Antibiotic—Medicine used to treat infections.
Enzyme—A type of protein, produced in the body,
that brings about or speeds up chemical reactions.
Gastrointestinal tract—The stomach, small intestine and large intestine.
Hypersecretory—Excessive production of a bodily
secretion. The most common hypersecretory
syndrome of the stomach is Zollinger-Ellison
Syndrome, a syndrome consisting of fulminating
intractable peptic ulcers, gastric hypersecretion and
hyperacidity, and the occurrence of gastrinomas
of the pancreatic cells of the islets of Langerhans.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.

The dose of sucralfate for acute ulcer therapy is
1 gram four times a day. After the ulcer has healed,
maintenance treatment may continue at 1 gram two
times daily.

Precautions
The proton pump inhibitors are generally well
tolerated, and the most common adverse effects are
diarrhea, itching, skin rash, dizziness and headache.
Muscle aches and a higher than normal rate of respiratory infections are among the other adverse reactions
reported. Omeprazole has an increased rate of fetal
deaths in animal studies. It is not known if these drugs
are excreted in human milk, but because of reported
adverse effects to infants in animal studies, it is recommended that proton pump inhibitors not be used by
nursing mothers.

Mucous—Thick fluid produced by the moist membranes that line many body cavities and structures.
Nonsteroidal anti-inflammatory drug (NSAID)—A
type of medicine used to relieve pain, swelling, and
other symptoms of inflammation, such as ibuprofen
or ketoprofen.

The H-2 receptor blockers vary widely in their
adverse effects. Although they are generally well tolerated, cimetidine may cause confusion in elderly
patients, and has an antiandrogenic effect that may
cause sexual dysfunction in males. Famotidine has
been reported to cause headache in 4.7% of patients.
It is advisable that mothers not take H-2 receptor
blockers while nursing.

Histamine H-2 receptor blockers stop the action
of histamine on the gastric parietal cells, inhibiting the
secretion of gastric acid. These drugs are less effective
than the proton pump inhibitors, but may achieve a
75–79% reduction in acid secretion. Higher rates of
acid inhibition may be achieved when the drug is
administered by the intravenous route. The H-2 receptor blockers may also be used to treat heartburn and
hypersecretory syndromes. When given before surgery, the H-2 receptor blockers are useful in prevention of aspiration pneumonia.

Sucralfate is well tolerated. It is poorly absorbed,
and its most common side effect is constipation in 2%
of patients. Diarrhea, nausea, vomiting, gastric discomfort, indigestion, flatulence, dry mouth, rash, pruritus (itching), back pain, headache, dizziness,
sleepiness, and vertigo have been reported, as well as
rare allergic responses. Because sucralfate releases
small amounts of aluminum into the system, it should
be used with caution in patients with renal insufficiency. There is no information available about sucralfate’s safety in breastfeeding.

Sucralfate (Carafate), a substituted sugar molecule
with no nutritional value, does not inhibit gastric acid,
but rather, reacts with existing stomach acid to form a
thick coating that covers the surface of an ulcer, protecting the open area from further damage. A secondary
effect is to act as an inhibitor of the digestive enzyme
pepsin. Sucralfate does not bind to the normal stomach
lining. The drug has been used for prevention of stress
ulcers, the type seen in patients exposed to physical stress
such as burns and surgery. It has no systemic effects.

Recommended dosage
The doses of the proton pump inhibitors and H-2
receptor blockers vary depending on the drug and
condition being treated. Consult individual references.
354

Interactions
Proton pump inhibitors may increase the pH of
the stomach. This will inactivate some antifungal
drugs that require an acid medium for effectiveness,
notable itraconazole and ketoconazole.
H-2 receptor blocking agents have a large number
of drug interactions. Consult individualized references.
Sucralfate should not be used with aluminum
containing antacids, because of the risk of increased
aluminum absorption. Sucralfate may inhibit
absorption and reduce blood levels of anticoagulants, digoxin, quinidine, ketoconazole, quinolones
and phenytoin.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

ORGANIZATIONS

Digestive Disease National Coalition. 507 Capitol Court
NE, Suite 200, Washington, DC 20003. (202) 544-7497.
National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570.
nddic@aerie.com. <http://www.niddk.nih.gov/
Brochures/NDDIC.htm>.
OTHER

Duodenal UlcerFact sheet. Johns Hopkins Health
Information Adult Health Advisor. <http://
csi.intelihealth.com>.
National Institute of Diabetes and Digestive and Kidney
Diseases. <http://www.niddk.nih.gov>.
PharmInfoNet’s Digestive Disease Center. <http://
pharminfo.com/disease.gastro.html>.
Stomach Ulcer (Gastric Ulcer). Fact sheet. Johns Hopkins
Health Information Adult Health Advisor. <http://
csi.intelihealth.com>.

Samuel D. Uretsky, PharmD

I Antiviral drugs
Definition
Antiviral drugs are medicines that cure or control
virus infections.

Purpose
Antivirals are used to treat infections caused by
viruses. Unlike antibacterial drugs, which may cover a
wide range of pathogens, antiviral agents tend to be
narrow in spectrum, and have limited efficacy.

Description
Exclusive of the antiretroviral agents used in HIV
(AIDS) therapy, there are currently only 11 antiviral
drugs available, covering four types of virus. Acyclovir
(Zovirax), famciclovir (Famvir), and valacyclovir
(Valtrex) are effective against herpesvirus, including
herpes zoster and herpes genitalis. They may also be of
value in either conditions caused by herpes, such as
chickenpox and shingles. These drugs are not curative,
but may reduce the pain of a herpes outbreak and
shorten the period of viral shedding.
Amantadine (Symmetrel), oseltamivir (Tamiflu),
rimantidine (Flumadine), and zanamivir (Relenza) are
useful in treatment of influenza virus. Amantadine,
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Asthenia—Muscle weakness.
Cytomegalovirus (CMV)—A type of virus that
attacks and enlarges certain cells in the body. The
virus also causes a disease in infants.
Herpes simplex—A virus that causes sores on the
lips (cold sores) or on the genitals (genital herpes).
HIV—Acronym for human immunodeficiency
virus, the virus that causes AIDS.
Parkinsonism—A group of conditions that all have
these typical symptoms in common: tremor, rigidity,
slow movement, and poor balance and coordination.
Pregnancy category—A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B: Animal
studies indicate no fetal risk, but no human studies,
or adverse effects in animals, but not in wellcontrolled human studies. Category C: No adequate
human or animal studies, or adverse fetal effects in
animal studies, but no available human data.
Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks
outweigh any benefits.
Prophylactic—Guarding from or preventing the
spread or occurrence of disease or infection.
Retrovirus—A group of viruses that contain RNA
and the enzyme reverse transcriptase. Many viruses
in this family cause tumors. The virus that causes
AIDS is a retrovirus.
Shingles—An disease caused by an infection with
the Herpes zoster virus, the same virus that causes
chickenpox. Symptoms of shingles include pain
and blisters along one nerve, usually on the face,
chest, stomach, or back.
Virus—A tiny, disease-causing structure that can
reproduce only in living cells and causes a variety
of infectious diseases.

rimantadine, and oseltamivir may be administered
throughout the flu season as preventatives for patients
who cannot take influenza virus vaccine.
Cidofovir (Vistide), foscarnet (Foscavir), and
ganciclovir (Cytovene) have been beneficial in treatment of cytomegalovirus in immunosupressed
patients, primarily HIV-positive patients and transplant recipients. Ribavirin (Virazole) is used to treat
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Antiviral drugs

Resources

Antiviral drugs

respiratory syncytial virus. In combination with
interferons, ribavirin has shown some efficacy
against hepatitis C, and there have been anecdotal
reports of utility against other types of viral
infections.
As a class, the antivirals are not curative, and
must be used either prophylactically or early in the
development of an infection. Their mechanism of
action is typically to inactivate the enzymes needed
for viral replication. This will reduce the rate of viral
growth, but will not inactive the virus already present.
Antiviral therapy must normally be initiated within 48
hours of the onset of an infection to provide any
benefit. Drugs used for influenza may be used
throughout the influenza season in high risk patients,
or within 48 hours of exposure to a known carrier.
Antiherpetic agents should be used at the first signs of
an outbreak. Anti-cytomegaloviral drugs must routinely be used as part of a program of secondary prophylaxis (maintenance therapy following an initial
response) in order to prevent reinfection in immunocompromised patients.

Recommended dosage
Dosage varies with the drug, patient age and condition, route of administration, and other factors. See
specific references.

Precautions
Ganciclovir is available in intravenous injection,
oral capsules, and intraoccular inserts. The capsules
should be reserved for prophylactic use in organ transplant patients, or for HIV infected patients who cannot be treated with the intravenous drug. The toxicity
profile of this drug when administered systemically
includes granulocytopenia, anemia and thrombocytopenia. The drug is in pregnancy category C, but has
caused significant fetal abnormalities in animal studies
including cleft palate and organ defects. Breast feeding
is not recommended.
Cidofovir causes renal toxicity in 53% of patients.
Patients should be well hydrated, and renal function
should be checked regularly. Other common adverse
effects are nausea and vomiting in 65% or patients,
asthenia in 46% and headache and diarrhea, both
reported in 27% of cases. The drug is category C in
pregnancy, due to fetal abnormalities in animal
studies. Breast feeding is not recommended.
Foscarnet is used in treatment of immunocompromised patients with cytomegalovirus infections
and in acyclovir-resistant herpes simples virus. The
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primary hazard is renal toxicity. Alterations in electrolyte levels may cause seizures. Foscarnet is category C during pregnancy. The drug has caused
skeletal abnormailities in developing fetuses. It is
not known whether foscarnet is excreted in breast
milk, however the drug does appear in breast milk in
animal studies.
Valaciclovir is metabolized to acyclovir, so that
the hazards of the two drugs are very similar. They
are generally well tolerated, but nausea and headache
are common adverse effects. They are both pregnancy category B. Although there have been no
reports of fetal abnormalities attributable to either
drug, the small number of reported cases makes it
impossible to draw conclusions regarding safety in
pregnancy. Acyclovir is found in breast milk, but
no adverse effects have been reported in the newborn. Famciclovir is similar in actions and adverse
effects.
Ribavirin is used by aerosol for treatment of hospitalized infants and young children with severe lower
respiratory tract infections due to respiratory syncytial
virus (RSV). When administered orally, the drug has
been used in adultys to treat other viral diseases
including acute and chronic hepatitis, herpes genitalis,
measles, and Lassa fever, however there is relatively
little information about these uses. In rare cases, initiation of ribavirin therapy has led to deterioration of
respiratory function in infants. Careful monitoring is
essential for safe use.
The anti-influenza drugs are generally well tolerated. Amantadine, which is also used for treatment
of Parkinsonism, may show more frequent CNS
effects, including sedation and dizziness. Rapid discontinuation of amantidine may cause an increase in
Parkinsonian symptoms in patients using the drug
for that purpose. All are schedule C for pregnancy.
In animal studies, they have caused fetal malformations in doses several times higher than the normal
human dose. Use caution in breast feeding.

Interactions
Consult specific references for information on
drug interactions.
Use particular caution in HIV-positive patients,
since these patients are commonly on multi-drug regimens with a high frequency of interactions.
Ganciclovir should not be used with other drugs
which cause hematologic toxicity, and cidofovir
should not be used with other drugs that may cause
kidney damage.
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Anxiety

Resources

KEY TERMS

PERIODICALS

Gray, Mary Ann. ‘‘Antiviral Medications.’’ Orthopaedic
Nursing 15 (November-December 1996): 82.

Samuel D. Uretsky, PharmD

I Anxiety
Definition
Anxiety is a multisystem response to a perceived
threat or danger. It reflects a combination of biochemical changes in the body, the patient’s personal history
and memory, and the social situation. As far as we
know, anxiety is a uniquely human experience. Other
animals clearly know fear, but human anxiety involves
an ability, to use memory and imagination to move
backward and forward in time, that animals do
not appear to have. The anxiety that occurs in posttraumatic syndromes indicates that human memory is
a much more complicated mental function than animal memory. Moreover, a large portion of human
anxiety is produced by anticipation of future events.
Without a sense of personal continuity over time,
people would not have the ‘‘raw materials’’ of anxiety.
It is important to distinguish between anxiety as a
feeling or experience, and an anxiety disorder as a
psychiatric diagnosis. A person may feel anxious without having an anxiety disorder. In addition, a person
facing a clear and present danger or a realistic fear is
not usually considered to be in a state of anxiety. In
addition, anxiety frequently occurs as a symptom in
other categories of psychiatric disturbance.

Affect—An observed emotional expression or
response. In some situations, anxiety would be
considered an inappropriate affect.
Anxiolytic—A type of medication that helps to
relieve anxiety.
Autonomic nervous system (ANS)—The part of the
nervous system that supplies nerve endings in the
blood vessels, heart, intestines, glands, and smooth
muscles, and governs their involuntary functioning.
The autonomic nervous system is responsible for
the biochemical changes involved in experiences
of anxiety.
Endocrine gland—A ductless gland, such as the
pituitary, thyroid, or adrenal gland, that secretes
its products directly into the blood or lymph.
Free-floating anxiety—Anxiety that lacks a definite
focus or content.
Hyperarousal—A state or condition of muscular
and emotional tension produced by hormones
released during the fight-or-flight reaction.
Hypothalamus—A portion of the brain that regulates the autonomic nervous system, the release of
hormones from the pituitary gland, sleep cycles,
and body temperature.
Limbic system—A group of structures in the brain
that includes the hypothalamus, amygdala, and
hippocampus. The limbic system plays an important part in regulation of human moods and emotions. Many psychiatric disorders are related to
malfunctioning of the limbic system.
Phobia—In psychoanalytic theory, a psychological
defense against anxiety in which the patient displaces anxious feelings onto an external object,
activity, or situation.

Description
Although anxiety is a commonplace experience
that everyone has from time to time, it is difficult to
describe concretely because it has so many different
potential causes and degrees of intensity. Doctors
sometimes categorize anxiety as an emotion or an
affect depending on whether it is being described by
the person having it (emotion) or by an outside observer (affect). The word emotion is generally used for the
biochemical changes and feeling state that underlie a
person’s internal sense of anxiety. Affect is used to
describe the person’s emotional state from an observer’s perspective. If a doctor says that a patient has an
anxious affect, he or she means that the patient
GALE ENCYCLOPEDIA OF MEDICINE

appears nervous or anxious, or responds to others in
an anxious way (for example, the individual is shaky,
tremulous, etc.).
Although anxiety is related to fear, it is not the
same thing. Fear is a direct, focused response to a
specific event or object, and the person is consciously
aware of it. Most people will feel fear if someone
points a loaded gun at them or if they see a tornado
forming on the horizon. They also will recognize that
they are afraid. Anxiety, on the other hand, is often
unfocused, vague, and hard to pin down to a specific
cause. In this form it is called free-floating anxiety.
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Anxiety

Sometimes anxiety being experienced in the present
may stem from an event or person that produced
pain and fear in the past, but the anxious individual
is not consciously aware of the original source of the
feeling. It is anxiety’s aspect of remoteness that makes
it hard for people to compare their experiences of it.
Whereas most people will be fearful in physically dangerous situations, and can agree that fear is an appropriate response in the presence of danger, anxiety is
often triggered by objects or events that are unique
and specific to an individual. An individual might be
anxious because of a unique meaning or memory
being stimulated by present circumstances, not
because of some immediate danger. Another individual looking at the anxious person from the outside
may be truly puzzled as to the reason for the person’s
anxiety.

Causes and symptoms
Anxiety can have a number of different causes. It is
a multidimensional response to stimuli in the person’s
environment, or a response to an internal stimulus (for
example, a hypochondriac’s reaction to a stomach
rumbling) resulting from a combination of general
biological and individual psychological processes.
Physical
In some cases, anxiety is produced by physical
responses to stress, or by certain disease processes or
medications.
THE AUTONOMIC NERVOUS SYSTEM (ANS). The nervous system of human beings is ‘‘hard-wired’’ to
respond to dangers or threats. These responses are
not subject to conscious control, and are the same in
humans as in lower animals. They represent an evolutionary adaptation to the animal predators and other
dangers with which all animals, including primitive
humans, had to cope. The most familiar reaction of
this type is the so-called ‘‘fight-or-flight’’ response.
This response is the human organism’s automatic
‘‘red alert’’ in a life-threatening situation. It is a state
of physiological and emotional hyperarousal marked
by high muscle tension and strong feelings of fear or
anger. When a person has a fight-or-flight reaction,
the level of stress hormones in their blood rises. They
become more alert and attentive, their eyes dilate, their
heartbeat increases, their breathing rate increases, and
their digestion slows down, allowing more energy to be
available to the muscles.

This emergency reaction is regulated by a part
of the nervous system called the autonomic nervous
system, or ANS. The ANS is controlled by the
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hypothalamus, a specialized part of the brainstem
that is among a group of structures called the limbic
system. The limbic system controls human emotions
through its connections to glands and muscles; it also
connects to the ANS and ‘‘higher’’ brain centers, such
as parts of the cerebral cortex. One problem with this
arrangement is that the limbic system cannot tell the
difference between a realistic physical threat and an
anxiety-producing thought or idea. The hypothalamus
may trigger the release of stress hormones by the
pituitary gland, even when there is no external and
objective danger. A second problem is caused by the
biochemical side effects of too many ‘‘false alarms’’ in
the ANS. When a person responds to a real danger,
his or her body gets rid of the stress hormones by
running away or by fighting. In modern life, however,
people often have fight-or-flight reactions in situations
in which they can neither run away nor lash out
physically. As a result, their bodies have to absorb all
the biochemical changes of hyperarousal, rather
than release them. These biochemical changes can
produce anxious feelings, as well as muscle tension
and other physical symptoms associated with anxiety.
They may even produce permanent changes in the
brain, if the process occurs repeatedly. Moreover,
chronic physical disorders, such as coronary artery
disease, may be worsened by anxiety, as chronic
hyperarousal puts undue stress on the heart, stomach,
and other organs.
DISEASES AND DISORDERS. Anxiety can be a symptom of certain medical conditions. Some of these diseases are disorders of the endocrine system, such as
Cushing’s syndrome (overproduction of cortisol by
the adrenal cortex), and include over- or underactivity
of the thyroid gland. Other medical conditions that
can produce anxiety include respiratory distress syndrome, mitral valve prolapse, porphyria, and chest
pain caused by inadequate blood supply to the heart
(angina pectoris).

A study released in 2004 showed that people who
had experienced traumatic bone injuries may have
unrecognized anxiety in the form of post-traumatic
stress disorder. This disorder can result from witnessing or experiencing an event involving serious injury,
or threatened death (or experiencing the death or
threatened death of another.)
MEDICATIONS AND SUBSTANCE USE. Numerous
medications may cause anxiety-like symptoms as a
side effect. They include birth control pills; some thyroid or asthma drugs; some psychotropic agents;
occasionally, local anesthetics; corticosteroids; antihypertensive drugs; and nonsteroidal anti-inflammatory
drugs (like flurbiprofen and ibuprofen).

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Withdrawal from certain prescription drugs,
primarily beta blockers and corticosteroids, can
cause anxiety. Withdrawal from drugs of abuse,
including LSD, cocaine, alcohol, and opiates, can
also cause anxiety.
Learned associations
Some aspects of anxiety appear to be unavoidable
byproducts of the human developmental process.
Humans are unique among animals in that they
spend an unusually long period of early life in a relatively helpless condition, and a sense of helplessness
can lead to anxiety. The extended period of human
dependency on adults means that people may remember, and learn to anticipate, frightening or upsetting
experiences long before they are capable enough to feel
a sense of mastery over their environment. In addition,
the fact that anxiety disorders often run in families
indicates that children can learn unhealthy attitudes
and behaviors from parents, as well as healthy ones.
Also, recurrent disorders in families may indicate that
there is a genetic or inherited component in some
anxiety disorders. For example, there has been found
to be a higher rate of anxiety disorders (panic) in
identical twins than in fraternal twins.
CHILDHOOD

DEVELOPMENT

AND

ANXIETY.

Researchers in early childhood development regard
anxiety in adult life as a residue of childhood memories of dependency. Humans learn during the first
year of life that they are not self-sufficient and that
their basic survival depends on the care of others. It is
thought that this early experience of helplessness
underlies the most common anxieties of adult life,
including fear of powerlessness and fear of being
unloved. Thus, adults can be made anxious by symbolic threats to their sense of competence and/or
significant relationships, even though they are no
longer helpless children.
SYMBOLIZATION. The psychoanalytic model gives
considerable weight to the symbolic aspect of human
anxiety; examples include phobic disorders, obsessions,
compulsions, and other forms of anxiety that are highly
individualized. The length of the human maturation
process allows many opportunities for children and
adolescents to connect their experiences with certain

GALE ENCYCLOPEDIA OF MEDICINE

objects or events that can bring back feelings in later
life. For example, a person who was frightened as a child
by a tall man wearing glasses may feel panicky years
later by something that reminds him of that person or
experience without consciously knowing why.
Freud thought that anxiety results from a person’s internal conflicts. According to his theory,
people feel anxious when they feel torn between
desires or urges toward certain actions, on the one
hand, and moral restrictions, on the other. In some
cases, the person’s anxiety may attach itself to an
object that represents the inner conflict. For example, someone who feels anxious around money may
be pulled between a desire to steal and the belief that
stealing is wrong. Money becomes a symbol for the
inner conflict between doing what is considered right
and doing what one wants.
PHOBIAS. Phobias are a special type of anxiety
reaction in which the person’s anxiety is concentrated
on a specific object or situation that the person then
tries to avoid. In most cases, the person’s fear is out of
all proportion to its ‘‘cause.’’ Prior to the Diagnostic
and Statistical Manual of Mental Disorders, 4th edition
(DSM-IV), these specific phobias were called simple
phobias. It is estimated that 10-11% of the population
will develop a phobia in the course of their lives. Some
phobias, such as agoraphobia (fear of open spaces),
claustrophobia (fear of small or confined spaces), and
social phobia, are shared by large numbers of people.
Others are less common or unique to the patient.

Social and environmental stressors
Anxiety often has a social dimension because
humans are social creatures. People frequently report
feelings of high anxiety when they anticipate and,
therefore, fear the loss of social approval or love.
Social phobia is a specific anxiety disorder that is
marked by high levels of anxiety or fear of embarrassment in social situations.
Another social stressor is prejudice. People who
belong to groups that are targets of bias are at higher
risk for developing anxiety disorders. Some experts
think, for example, that the higher rates of phobias
and panic disorder among women reflects their greater
social and economic vulnerability.
Some controversial studies indicate that the
increase in violent or upsetting pictures and stories in
news reports and entertainment may raise the anxiety
level of many people. Stress and anxiety management
programs often suggest that patients cut down their
exposure to upsetting stimuli.
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Anxiety

Although people do not usually think of caffeine as
a drug, it can cause anxiety-like symptoms when consumed in sufficient quantity. Patients who consume caffeine rich foods and beverages, such as chocolate, cocoa,
coffee, tea, or carbonated soft drinks (especially cola
beverages), can sometimes lower their anxiety symptoms
simply by reducing their intake of these substances.

Anxiety

Anxiety may also be caused by environmental or
occupational factors. People who must live or work
around sudden or loud noises, bright or flashing lights,
chemical vapors, or similar nuisances, which they cannot
avoid or control, may develop heightened anxiety levels.
Existential anxiety
Another factor that shapes human experiences of
anxiety is knowledge of personal mortality. Humans are
the only animals that appear to be aware of their limited
life span. Some researchers think that awareness of
death influences experiences of anxiety from the time
that a person is old enough to understand death.
Symptoms of anxiety
In order to understand the diagnosis and treatment of anxiety, it is helpful to have a basic understanding of its symptoms.
SOMATIC. The somatic or physical symptoms of

anxiety include headaches, dizziness or lightheadedness, nausea and/or vomiting, diarrhea, tingling, pale
complexion, sweating, numbness, difficulty in breathing, and sensations of tightness in the chest, neck,
shoulders, or hands. These symptoms are produced
by the hormonal, muscular, and cardiovascular reactions involved in the fight-or-flight reaction. Children
and adolescents with generalized anxiety disorder show
a high percentage of physical complaints.
BEHAVIORAL. Behavioral symptoms of anxiety
include pacing, trembling, general restlessness, hyperventilation, pressured speech, hand wringing, or finger
tapping.
COGNITIVE. Cognitive symptoms of anxiety
include recurrent or obsessive thoughts, feelings of
doom, morbid or fear-inducing thoughts or ideas,
and confusion, or inability to concentrate.
EMOTIONAL. Feeling states associated with anxiety include tension or nervousness, feeling ‘‘hyper’’ or
‘‘keyed up,’’ and feelings of unreality, panic, or terror.
DEFENSE MECHANISMS. In psychoanalytic theory,
the symptoms of anxiety in humans may arise from or
activate a number of unconscious defense mechanisms. Because of these defenses, it is possible for a
person to be anxious without being consciously
aware of it or appearing anxious to others. These
psychological defenses include:


Repression. The person pushes anxious thoughts or
ideas out of conscious awareness.



Displacement. Anxiety from one source is attached
to a different object or event. Phobias are an example

360

of the mechanism of displacement in psychoanalytic
theory.


Rationalization. The person justifies the anxious
feelings by saying that any normal person would
feel anxious in their situation.



Somatization. The anxiety emerges in the form of
physical complaints and illnesses, such as recurrent
headaches, stomach upsets, or muscle and joint pain.



Delusion formation. The person converts anxious
feelings into conspiracy theories or similar ideas
without reality testing. Delusion formation can
involve groups as well as individuals.

Other theorists attribute some drug addiction to the
desire to relieve symptoms of anxiety. Most addictions,
they argue, originate in the use of mood-altering substances or behaviors to ‘‘medicate’’ anxious feelings.

Diagnosis
The diagnosis of anxiety is difficult and complex
because of the variety of its causes and the highly
personalized and individualized nature of its symptom
formation. There are no medical tests that can be used
to diagnose anxiety by itself. When a doctor examines
an anxious patient, he or she will first rule out physical
conditions and diseases that have anxiety as a symptom. Apart from these exclusions, the physical examination is usually inconclusive. Some anxious patients
may have their blood pressure or pulse rate affected by
anxiety, or may look pale or perspire heavily, but
others may appear physically completely normal.
The doctor will then take the patient’s medication,
dietary, and occupational history to see if they are
taking prescription drugs that might cause anxiety, if
they are abusing alcohol or mood-altering drugs,
if they are consuming large amounts of caffeine, or if
their workplace is noisy or dangerous. In most cases,
the most important source of diagnostic information is
the patient’s psychological and social history. The
doctor may administer a brief psychological test to
help evaluate the intensity of the patient’s anxiety and
some of its features. Some tests that are often given
include the Hamilton Anxiety Scale and the Anxiety
Disorders Interview Schedule (ADIS). Many doctors
will check a number of chemical factors in the blood,
such as the level of thyroid hormone and blood sugar.

Treatment
Not all patients with anxiety require treatment,
but for more severe cases, treatment is recommended.
Because anxiety often has more than one cause and is
experienced in highly individual ways, its treatment
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Medications
Medications are often prescribed to relieve the
physical and psychological symptoms of anxiety.
Most agents work by counteracting the biochemical
and muscular changes involved in the fight-or-flight
reaction. Some work directly on the chemicals in the
brain that are thought to underlie the anxiety.
ANXIOLYTICS. Anxiolytics are sometimes called
tranquilizers. Most anxiolytic drugs are either benzodiazepines or barbiturates. Barbiturates, once commonly used, are now rarely used in clinical practice.
Barbiturates work by slowing down the transmission
of nerve impulses from the brain to other parts
of the body. They include such drugs as phenobarbital
(Luminal) and pentobarbital (Nembutal). Benzodiazepines work by relaxing the skeletal muscles and
calming the limbic system. They include such drugs
as chlordiazepoxide (Librium) and diazepam
(Valium). Both barbiturates and benzodiazepines are
potentially habit-forming and may cause withdrawal
symptoms, but benzodiazepines are far less likely than
barbiturates to cause physical dependency. Both drugs
also increase the effects of alcohol and should never be
taken in combination with it.

Two other types of anxiolytic medications
include meprobamate (Equanil), which is now
rarely used, and buspirone (BuSpar), a new type
of anxiolytic that appears to work by increasing
the efficiency of the body’s own emotion-regulating
brain chemicals. Buspirone has several advantages
over other anxiolytics. It does not cause dependence problems, does not interact with alcohol,
and does not affect the patient’s ability to drive
or operate machinery. However, buspirone is not
effective against certain types of anxiety, such as
panic disorder.
ANTIDEPRESSANTS AND BETA-BLOCKERS. For some
anxiety disorders, such as obsessive-compulsive disorder and panic type anxiety, a type of drugs used to treat
depression, selective serotonin reuptake inhibitors
(SSRIs; such as Prozac and Paxil), are the treatment
of choice. A newer drug that has been shown as effective as Paxil is called escitalopram oxalate (Lexapro).
Because anxiety often coexists with symptoms of

GALE ENCYCLOPEDIA OF MEDICINE

depression, many doctors prescribe antidepressant
medications for anxious/depressed patients. While
SSRIs are more common, antidepressants are sometimes prescribed, including tricyclic antidepressants
such as imipramine (Tofranil) or monoamine oxidase
inhibitors (MAO inhibitors) such as phenelzine
(Nardil).
Beta-blockers are medications that work by
blocking the body’s reaction to the stress hormones
that are released during the fight-or-flight reaction.
They include drugs like propranolol (Inderal) or atenolol (Tenormin). Beta-blockers are sometimes given
to patients with post-traumatic anxiety symptoms.
More commonly, the beta-blockers are given to
patients with a mild form of social phobic anxiety,
such as fear of public speaking.
Psychotherapy
Most patients with anxiety will be given some
form of psychotherapy along with medications.
Many patients benefit from insight-oriented therapies,
which are designed to help them uncover unconscious
conflicts and defense mechanisms in order to understand how their symptoms developed. Patients who
are extremely anxious may benefit from supportive
psychotherapy, which aims at symptom reduction
rather than personality restructuring.
Two newer approaches that work well with
anxious patients are cognitive-behavioral therapy
(CBT), and relaxation training. In CBT, the patient
is taught to identify the thoughts and situations that
stimulate his or her anxiety, and to view them more
realistically. In the behavioral part of the program, the
patient is exposed to the anxiety-provoking object,
situation, or internal stimulus (like a rapid heart
beat) in gradual stages until he or she is desensitized
to it. Relaxation training, which is sometimes called
anxiety management training, includes breathing exercises and similar techniques intended to help the
patient prevent hyperventilation and relieve the muscle tension associated with the fight-or-flight reaction.
Both CBT and relaxation training can be used in
group therapy as well as individual treatment. In addition to CBT, support groups are often helpful to
anxious patients, because they provide a social network and lessen the embarrassment that often accompanies anxiety symptoms.
Psychosurgery
Surgery on the brain is very rarely recommended
for patients with anxiety; however, some patients with
severe cases of obsessive-compulsive disorder (OCD)
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Anxiety

usually requires more than one type of therapy. In
addition, there is no way to tell in advance how
patients will respond to a specific drug or therapy.
Sometimes the doctor will need to try different medications or methods of treatment before finding the
best combination for the particular patient. It usually
takes about six to eight weeks for the doctor to evaluate the effectiveness of a treatment regimen.

Anxiety disorders

have been helped by an operation on a part of
the brain that is involved in OCD. Normally, this
operation is attempted after all other treatments have
failed.

American Academy of Child and Adolescent Psychiatry
(June 2004): 752–761.
‘‘Patients With Traumatic Bone Injuries Have Unrecognized
Anxiety.’’ Health & Medicine Week (June 28, 2004): 824.

Rebecca J. Frey, PhD
Teresa G. Odle

Alternative treatment
Alternative treatments for anxiety cover a variety
of approaches. Meditation and mindfulness training
are thought beneficial to patients with phobias and
panic disorder. Hydrotherapy is useful to some
anxious patients because it promotes general relaxation of the nervous system. Yoga, aikido, t’ai chi, and
dance therapy help patients work with the physical, as
well as the emotional, tensions that either promote
anxiety or are created by the anxiety.
Homeopathy and traditional Chinese medicine
approach anxiety as a symptom of a systemic disorder.
Homeopathic practitioners select a remedy based on
other associated symptoms and the patient’s general
constitution. Chinese medicine regards anxiety as a
blockage of qi, or vital force, inside the patient’s
body that is most likely to affect the lung and large
intestine meridian flow. The practitioner of Chinese
medicine chooses acupuncture point locations and/or
herbal therapy to move the qi and rebalance the entire
system in relation to the lung and large intestine.

Prognosis
The prognosis for resolution of anxiety depends
on the specific disorder and a wide variety of factors,
including the patient’s age, sex, general health, living
situation, belief system, social support network, and
responses to different anxiolytic medications and
forms of therapy.

Prevention
Humans have significant control over thoughts,
and, therefore, may learn ways of preventing anxiety
by changing irrational ideas and beliefs. Humans
also have some power over anxiety arising from
social and environmental conditions. Other forms
of anxiety, however, are built into the human organism and its life cycle, and cannot be prevented or
eliminated.
Resources
PERIODICALS

‘‘Lexapro Found to be as Effective as Paxil.’’ Mental Health
Weekly Digest (April 12, 2004): 16.
Masi, Gabriele, et al. ‘‘Generalized Anxiety Disorder in
Referred Children and Adolescents.’’ Journal of the
362

I Anxiety disorders
Definition
The anxiety disorders are a group of mental disturbances characterized by anxiety as a central or core
symptom. Although anxiety is a commonplace experience, not everyone who experiences it has an anxiety
disorder. Anxiety is associated with a wide range of
physical illnesses, medication side effects, and other
psychiatric disorders.
The revisions of the Diagnostic and Statistical
Manual of Mental Disorders (DSM) that took place
after 1980 brought major changes in the classification
of the anxiety disorders. Prior to 1980, psychiatrists
classified patients on the basis of a theory that defined
anxiety as the outcome of unconscious conflicts in the
patient’s mind. DSM-III (1980), DSM-III-R (1987),
and DSM-IV (1994) introduced and refined a new
classification that considered recent discoveries
about the biochemical and post-traumatic origins
of some types of anxiety. The present definitions
are based on the external and reported symptom
patterns of the disorders rather than on theories
about their origins.

Description
Anxiety disorders are the most common form of
mental disturbance in the United States population. It is
estimated that 28 million people suffer from an anxiety
disorder every year. These disorders are a serious problem for the entire society because of their interference
with patients’ work, schooling, and family life. They
also contribute to the high rates of alcohol and substance abuse in the United States. Anxiety disorders
are an additional problem for health professionals
because the physical symptoms of anxiety frequently
bring people to primary care doctors or emergency
rooms.
DSM-IV defines 12 types of anxiety disorders in
the adult population. They can be grouped under
seven headings:
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Panic disorders with or without agoraphobia. The
chief characteristic of panic disorder is the occurrence
of panic attacks coupled with fear of their recurrence.
In clinical settings, agoraphobia is usually not a disorder byitself, but is typically associated with some
form of panic disorder. Patients with agoraphobia
are afraid of places or situations in which they might
have a panic attack and be unable to leave or to find
help. About 25% of patients with panic disorder
develop obsessive-compulsive disorder (OCD).
Phobias. These include specific phobias and social
phobia. A phobia is an intense irrational fear of a
specific object or situation that compels the patient
to avoid it. Some phobias concern activities or
objects that involve some risk (for example, flying
or driving) but many are focused on harmless animals or other objects. Social phobia involves a fear of
being humiliated, judged, or scrutinized. It manifests
itself as a fear of performing certain functions in the
presence of others, such as public speaking or using
public lavatories.

KEY TERMS
Agoraphobia—Abnormal anxiety regarding public
places or situations from which the patient may
wish to flee or in which he or she would be helpless
in the event of a panic attack.
Compulsion—A repetitive or ritualistic behavior
that a person performs to reduce anxiety.
Compulsions often develop as a way of controlling
or ‘‘undoing’’ obsessive thoughts.
Obsession—A repetitive or persistent thought,
idea, or impulse that is perceived as inappropriate
and distressing.
Panic attack—A time-limited period of intense fear
accompanied by physical and cognitive symptoms.
Panic attacks may be unexpected or triggered by
specific cues.



Obsessive-compulsive disorder (OCD). This disorder
is marked by unwanted, intrusive, persistent
thoughts or repetitive behaviors that reflect the
patient’s anxiety or attempts to control it. It affects
between 2-3% of the population and is much more
common than was previously thought.

medical conditions or substance abuse are less ageand gender-specific. Whereas OCD affects males and
females equally, GAD, panic disorder, and specific
phobias all affect women more frequently than men.
GAD and panic disorders are more likely to develop in
young adults, while phobias and OCD can begin in
childhood.



Stress disorders. These include post-traumatic stress
disorder (PTSD) and acute stress disorder. Stress
disorders are symptomatic reactions to traumatic
events in the patient’s life.

Anxiety disorders in children and adolescents



Generalized anxiety disorder (GAD). GAD is the
most commonly diagnosed anxiety disorder and
occurs most frequently in young adults.



Anxiety disorders due to known physical causes.
These include general medical conditions or substance abuse.



Anxiety disorder not otherwise specified. This last
category is not a separate type of disorder, but is
included to cover symptoms that do not meet the
specific DSM-IV criteria for other anxiety disorders.

All DSM-IV anxiety disorder diagnoses include a
criterion of severity. The anxiety must be severe
enough to interfere significantly with the patient’s
occupational or educational functioning, social activities or close relationships, and other customary
activities.
The anxiety disorders vary widely in their frequency of occurrence in the general population, age
of onset, family patterns, and gender distribution. The
stress disorders and anxiety disorders caused by
GALE ENCYCLOPEDIA OF MEDICINE

DSM-IV defines one anxiety disorder as specific
to children, namely, separation anxiety disorder. This
disorder is defined as anxiety regarding separation
from home or family that is excessive or inappropriate
for the child’s age. In some children, separation anxiety takes the form of school avoidance.
Children and adolescents can also be diagnosed
with panic disorder, phobias, generalized anxiety disorder, and the post-traumatic stress syndromes.

Causes and symptoms
The causes of anxiety include a variety of individual and general social factors, and may produce physical, cognitive, emotional, or behavioral symptoms.
The patient’s ethnic or cultural background may also
influence his or her vulnerability to certain forms of
anxiety. Genetic factors that lead to biochemical
abnormalities may also play a role.
Anxiety in children may be caused by suffering
from abuse, as well as by the factors that cause anxiety
in adults.
363

Anxiety disorders



Anxiety disorders

Diagnosis
The diagnosis of anxiety disorders is complicated by
the variety of causes of anxiety and the range of disorders that may include anxiety as a symptom. Many
patients who suffer from anxiety disorders have features
or symptoms of more than one disorder. Patients whose
anxiety is accounted for by another psychic disorder,
such as schizophrenia or major depression, are not
diagnosed with an anxiety disorder. A doctor examining
an anxious patient will usually begin by ruling out diseases that are known to cause anxiety and then proceed
to take the patient’s medication history, in order to
exclude side effects of prescription drugs. Most doctors
will ask about caffeine consumption to see if the
patient’s dietary habits are a factor. The patient’s work
and family situation will also be discussed. Often, primary care physicians will exhaust resources looking for
medical causes for general patient complaints which
may indicate a physical illness. In 2004, the Anxiety
Disorders Association of American published guidelines to better aid physicians in diagnosing and managing generalized anxiety disorder. Laboratory tests for
blood sugar and thyroid function are also common.
Diagnostic testing for anxiety
There are no laboratory tests that can diagnose
anxiety, although the doctor may order some specific
tests to rule out disease conditions. Although there is
no psychiatric test that can provide definite diagnoses
of anxiety disorders, there are several short-answer
interviews or symptom inventories that doctors can
use to evaluate the intensity of a patient’s anxiety
and some of its associated features. These measures
include the Hamilton Anxiety Scale and the Anxiety
Disorders Interview Schedule (ADIS).

Treatment
For relatively mild anxiety disorders, psychotherapy alone may suffice. In general, doctors prefer to use
a combination of medications and psychotherapy with
more severely anxious patients. Most patients respond
better to a combination of treatment methods than to
either medications or psychotherapy in isolation.
Because of the variety of medications and treatment
approaches that are used to treat anxiety disorders, the
doctor cannot predict in advance which combination
will be most helpful to a specific patient. In many cases
the doctor will need to try a new medication or treatment over a six- to eight-week period in order to assess
its effectiveness. Treatment trials do not necessarily
mean that the patient cannot be helped or that the
doctor is incompetent.
364

Although anxiety disorders are not always easy to
diagnose, there are several reasons why it is important
for patients with severe anxiety symptoms to get help.
Anxiety doesn’t always go away by itself; it often
progresses to panic attacks, phobias, and episodes of
depression. Untreated anxiety disorders may eventually lead to a diagnosis of major depression, or
interfere with the patient’s education or ability to
keep a job. In addition, many anxious patients develop
addictions to drugs or alcohol when they try to ‘‘medicate’’ their symptoms. Moreover, since children learn
ways of coping with anxiety from their parents, adults
who get help for anxiety disorders are in a better
position to help their families cope with factors that
lead to anxiety than those who remain untreated.

Alternative treatment
Alternative treatments for anxiety cover a variety
of approaches. Meditation and mindfulness training
are thought beneficial to patients with phobias and
panic disorder. Hydrotherapy is useful to some
anxious patients because it promotes general relaxation of the nervous system. Yoga, aikido, t’ai chi, and
dance therapy help patients work with the physical, as
well as the emotional, tensions that either promote
anxiety or are created by the anxiety.
Homeopathy and traditional Chinese medicine
approach anxiety as a symptom of a systemic disorder.
Homeopathic practitioners select a remedy based on
other associated symptoms and the patient’s general
constitution. Chinese medicine regards anxiety as a
blockage of qi, or vital force, inside the patient’s
body that is most likely to affect the lung and large
intestine meridian flow. The practitioner of Chinese
medicine chooses acupuncture point locations and/or
herbal therapy to move the qi and rebalance the entire
system in relation to the lung and large intestine.

Prognosis
The prognosis for recovery depends on the specific disorder, the severity of the patient’s symptoms, the
specific causes of the anxiety, and the patient’s degree
of control over these causes.

Prevention
Anxiety is an unavoidable feature of human existence. However, humans have some power over their
reactions to anxiety-provoking events and situations.
Cognitive therapy and meditation or mindfulness
training appear to be beneficial in helping people
lower their long-term anxiety levels.
GALE ENCYCLOPEDIA OF MEDICINE

Aortic aneurysm

Resources
PERIODICALS

‘‘Guidelines to Assist Primary Care Physicians in Diagnosing
GAD.’’ Psychiatric Times (July 1, 2004): 16.

Rebecca J. Frey, PhD
Teresa G. Odle

Anxiolytics see Antianxiety drugs

I Aortic aneurysm
Definition

Surgery being performed to correct aortic aneurysm. (Custom
Medical Stock Photo. Reproduced by permission.)

An aneurysm is an abnormal bulging or swelling
of a portion of a blood vessel. The aorta, which can
develop these abnormal bulges, is the large blood
vessel that carries oxygen-rich blood away from the
heart to the rest of the body.

Description
The aorta carries oxygen-rich blood to the body,
and is therefore called an artery. Because the aorta is an
artery, its walls are made of up three layers; a thin inner
layer, a muscular middle layer (that gives the vessel its
flexibility under pressure from the filling blood), and a
fiber-like outer layer that gives the vessel strength to not
burst when the heart pumps blood to the body.
Aortic aneurysms occur when a weakness develops in part of the wall of the aorta; three basic
types are usually found. If all three layers of the
vessel are affected and weakness develops along an
extended area of the vessel, the weakened area will
appear as a large, bulging region of blood vessel;
this is called a fusiform aneurysm. If weakness
develops between the inner and outer layers of the
aortic wall, a bulge results as blood from the interior of the vessel is pushed around the damaged
region in the wall and collects between these layers.
This is called a dissecting aneurysm because one
layer is ‘‘dissected’’ or separated from another. If
damage occurs to only the middle (muscular) layer
of the vessel, a sack-like bulge can form; therefore,
this is a saccular aneurysm.

Causes and symptoms
Aortic aneurysms occur in different portions of
the aorta, which begins in the chest (at the heart) and
travels downward through the abdomen. Aneurysms
found in the region of the aorta within the chest are
GALE ENCYCLOPEDIA OF MEDICINE

An aneurysm in progress. An aneurysm is an abnormal
bulging or swelling of a portion of a blood vessel. (Custom
Medical Stock Photo. Reproduced by permission.)

called thoracic aortic aneurysms. Aneurysms that
occur in the part of the aorta within the abdomen are
called abdominal aortic aneurysms.
Thoracic aortic aneurysms do not usually produce any noticeable symptoms. However, as the
aneurysm becomes larger, chest, shoulder, neck,
lower back, or abdominal pain can result.
Abdominal aortic aneurysms occur more often in
men, and these aneurysms can cause pain in the
lower back, hips, and abdomen. A painful abdominal aortic aneurysm usually means that the aneurysm
could burst very soon.
Most abdominal aortic aneurysms are caused by
atherosclerosis, a condition caused when fat (mostly
cholesterol) carried in the blood builds up in the inner
wall of the aorta. As more and more fat attaches to the
aortic wall, the wall itself becomes abnormally weak
and often results in an aneurysm or bulge.
365

Aortic aneurysm

Carotid artery

Subclavian artery
Aorta
Hepatic artery

Pulmonary artery
Heart

Renal artery

Liver

Messentric artery

Kidney

Iliac artery

Aortic
aneurysm

Aortic aneurysms occur when a weakness develops in a part of the wall of the aorta. The aorta is the large blood vessel that
carries oxygen-rich blood away from the heart to the rest of the body. (Illustration by Electronic Illustrators Group.)

Diagnosis

KEY TERMS
Atherosclerosis—The accumulation of fat on the
inner wall of an artery. This fat is largely made up
of cholesterol being carried in the blood.
Dacron—A synthetic polyester fiber used to surgically repair damaged sections of blood vessel walls.

Silent, stable aneurysms are often detected when a
person has an x ray as part of a routine examination or
for other medical reasons. Otherwise, when chest,
abdominal, or back pain is severe, aortic aneurysm is
suspected and x-ray (radiographic) studies can confirm or rule out that condition.

Treatment
Aortic aneurysms are also caused by a breakdown
of the muscular middle layer of the artery wall, by high
blood pressure, by direct injury to the chest, and
although rare, by bacteria that can infect the aorta.
366

Aortic aneurysms are potentially life-threatening
conditions. Small aneurysms should be monitored for
their rate of growth and large aneurysms require consideration for a surgical repair. The most common
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Dissection—A cut or divide.
Hemorrhage—A large discharge of blood, profuse
bleeding.

Prognosis
Only 1-2% of people die from having surgical
repair of an aortic aneurysm. However, if the aneurysm
is untreated and eventually ruptures, less than half of
the people with ruptured aneurysms will survive. The
challenge for the physician is to decide when or if to do
the preventive surgery.

Prevention
Aneuryms can develop in people with atherosclerosis. High blood pressure can also lead to this
condition. Although no definite prevention exists, lifestyle and dietary changes that help lower blood pressure and the amount of fat in the blood stream may
slow the development of aneurysms.
Resources
PERIODICALS

van der Vleit, J. Adam, and Albert P. M. Boll. ‘‘Abdominal
Aortic Aneurysm.’’ The Lancet 349 (March 22, 1997): 863.

pressure. When a defect develops, blood pressure can
force the tear to open and allow blood to pass through.
Since the blood is under pressure, it eventually splits
(dissecting) the middle layer of the blood vessel, creating a new channel for blood. The length of the channel
grows over time and can result in the closing off of
connection points to other arteries. This can lead to
heart attack, strokes, abdominal pain, and nerve
damage. Blood may leak from the dissection and collect in the chest an around the heart.
A second mechanism leading to aortic dissection
is medial hemorrhage. A medial hemorrhage occurs in
the middle layer of the blood vessel and spills through
the inner lining of the aorta wall. This opening then
allows blood from the aorta to enter the vessel wall
and begin a dissection. Approximately 2,000 cases of
aortic dissection occur yearly in the United States.

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Dominic De Bellis, PhD

I Aortic dissection
Definition
Aortic dissection is a rare, but potentially fatal,
condition in which blood passes through the inner
lining and between the layers of the aorta. The dissecting aorta usually does not burst, but has an abnormal
second channel within it.

Description
A defect in the inner lining of the aorta allows an
opening or tear to develop. The aorta is the main
artery of the body and is an area of high blood
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Aortic dissection is caused by a deterioration of
the inner lining of the aorta. There are a number of
conditions that predispose a person to develop defects
of the inner lining, including high blood pressure,
Marfan’s disease, Ehlers-Danlos syndrome, connective
tissue diseases, and defects of heart development
which begin during fetal development. A dissection
can also occur accidentally following insertion of a
catheter, trauma, or surgery. The main symptom is sudden, intense pain. The pain can be so intense as to
immobilize the patient and cause him to fall to the
ground. The pain is frequently felt in both the chest
and in the back, between the shoulder blades. The extent
of the pain is proportional to the length of the dissection.

Diagnosis
The pain experienced by the patient is the first
symptom of aortic dissection and is unique. The pain is
usually described by the patient as ‘‘tearing, ripping, or
stabbing.’’ This is in contrast to the pain associated with
heart attacks. The patient frequently has a reduced or
absent pulse in the extremities. A murmur may be heard
if the dissection is close to the heart. An enlarged aorta
will usually appear in the chest x rays and ultrasound
367

Aortic dissection

method of surgical repair is to cut out the bulging
section of artery wall and sew a Dacron fiber material
into its place in the vessel wall.

Aortic valve insufficiency

exams of most patients. The use of a blood dye in angiograms and/or CT scans (computed tomography scans)
will aid in diagnosing and visualizing the dissection.

Treatment
Because of the potentially fatal nature of aortic
dissection, patients are treated immediately. Drugs are
administered to reduce the blood pressure and heart
rate. If the dissection is small, drug therapy alone may
be used. In other cases, surgery is performed. In surgery, damaged sections of the aorta are removed and a
synthetic graft is often used to reconstruct the
damaged vessel.

Diseased valve
Normal
blood flow

Prognosis
Depending on the nature and extent of the dissection, death can occur within a few hours of the start of
a dissection. Approximately 75% of untreated people
die within two weeks of the start of a dissection. Of
those who are treated, 40% survive more than 10
years. Patients are usually given long term treatment
with drugs to reduce their blood pressure, even if they
have had surgery.

Blood backflow

A human heart with a diseased valve that doesn’t open and
close properly, allowing blood to backflow to the heart.
(Illustration by Argosy, Inc.)

Resources
BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, editors. The
Heart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD

Aortic incompetence see Aortic valve
insufficiency
Aortic regurgitation see Aortic valve
insufficiency
Aortic stenosis see Aortic valve stenosis

Description
Aortic valve insufficiency occurs when this
valve cannot properly close after blood that is leaving the heart’s left ventricle enters the aorta. With
each contraction of the heart more and more blood
flows back into the left ventricle, causing the ventricle to become overfilled. This larger-than-normal
amount of blood that collects in the left ventricle
puts pressure on the walls of the heart, causing the
heart muscle to increase in thickness (hypertrophy).
If this thickening continues, the heart can be permanently damaged.
Aortic valve insufficiency is also know as aortic valve
regurgitation because of the abnormal reversed flow of
blood leaking through the poorly functioning valve.

I Aortic valve insufficiency
Definition
The aortic valve separates the left ventricle of the
heart (the heart’s largest pumping chamber) from the
aorta, the large artery that carries oxygen-rich blood out
of the left ventricle to the rest of the body. In aortic valve
insufficiency, the aortic valve becomes leaky, causing
blood to flow backwards into the left ventricle.
368

Causes and symptoms
The faulty working of the aortic valve can be
caused by a birth defect; by abnormal widening
of the aorta (which can be caused by very high blood
pressure and a variety of other less common conditions); by various diseases that cause large amounts of
swelling (inflammation) in different areas of the body,
like rheumatic fever; and, although rarely, by the sexually transmitted disease, syphilis.
GALE ENCYCLOPEDIA OF MEDICINE

Rheumatic fever—A disease believed to be caused
by a bacterium named group A streptococcus. This
bacterium causes a sore ‘‘strep throat’’ and can also
result in fever. Infection by this bacterium can also
damage the heart and its valves, but how this takes
place is not clearly understood.

Although drug treatment can help put off the need
for surgical valve replacement, it is important to
replace the faulty valve before the heart muscle itself
is damaged beyond recovery.
Resources
PERIODICALS

Condos Jr., William R. ‘‘Decade-old Heart Drug May Have a
New Use.’’ San Diego Business Journal 18 (21 July 1997): 24.
ORGANIZATIONS

About 75% of people with aortic valve insufficiency are men. Rheumatic (inflammatory) diseases
have been the main cause of this condition in both
men and women.
Aortic valve insufficiency can remain unnoticed
for 10 to 15 years. In cases of severe insufficiency a
person may notice a variety of symptoms, including an
uncomfortable pounding of the heart when lying
down, a very rapid or hard heart beat (palpitations),
shortness of breath, chest pain, and if untreated for
very long times, swelling of the liver, ankles, and belly.

Diagnosis
A poorly functioning or insufficient aortic valve
can be identified when a doctor listens to the heart
during a physical examination. A chest x ray, an electrocardiogram (ECG, an electrical printout of the heart
beats), as well as an echocardiogram (a test that uses
sound waves to create an image of the heart and its
valves), can further evaluate or confirm the condition.

Treatment
Aortic insufficiency is usually corrected by having
the defective valve surgically replaced. However, such
an operation is done in severe cases. Before the condition worsens, certain drugs can be used to help manage
this condition.
Drugs that remove water from the body, drugs
that lower blood pressure, and drugs that help the
heart beat more effectively can each be used for this
condition. Reducing the amount of salt in the diet also
helps lower the amount of fluid the body holds and can
help the heart to work more efficiently as well.
In cases of a severely malfunctioning valve that
has been untreated for a long time, surgery is the
treatment of choice, especially if the heart is not functioning normally. Human heart valves can be replaced
with man-made valves or with valves taken from pig
hearts.
GALE ENCYCLOPEDIA OF MEDICINE

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Dominic De Bellis, PhD

I Aortic valve stenosis
Definition
When aortic valve stenosis occurs, the aortic
valve, located between the aorta and left ventricle of
the heart, is narrower than normal size.

Description
A normal aortic valve, when open, allows the free
flow of blood from the left ventricle to the aorta. When
the valve narrows, as it does with stenosis, blood flow
is impeded. Because it is more difficult for blood
to flow through the valve, there is increased strain on
the heart. This can cause the left ventricle to enlarge
and malfunction, resulting in reduced blood supply to
the heart muscle and body, as well as fluid build up in
the lungs.

Cause and symptoms
Aortic valve stenosis can occur because of a birth
defect in the formation of the valve. Calcium deposits
may form on the valve with aging, causing the valve to
become stiff and narrow. Stenosis can also occur as a
result of rheumatic fever. Mild aortic stenosis may
produce no symptoms at all. The most common symptoms, depending on the severity of the disease, are
chest pain, blackouts, and difficulty breathing.
369

Aortic valve stenosis

Prognosis

KEY TERMS

Aortic valve stenosis

KEY TERMS
Aorta—The largest artery in the body, which
moves blood from the left ventricle to the rest of
the body.
ECG—Also called an electrocardiogram, it records
the electrical activity of the heart.
Echocardiogram—A procedure in which high frequency sound waves harmlessly bounce off organs
in the body providing an image so one can determine their structure and function.
A close-up view of a calcified stenosis of the aortic valve.
(Custom Medical Stock Photo. Reproduced by permission.)

Diagnosis
Using a stethoscope, a physician may hear a murmur and other abnormal heart sounds. An ECG, also
called an electrocardiogram, records the electrical
activity of the heart. This technique and chest x ray
can show evidence that the left ventricle is enlarged.
An x ray can also reveal calcium deposits on the valve,
as well as congestion in the lungs. Echocardiography
can pick up thickening of the valve, heart size, and
whether or not the valve is working properly. This is
a procedure in which high frequency sound waves
harmlessly bounce off organs in the body. Cardiac
catheterization, in which a contrast dye is injected in
an artery using a catheter, is the key tool to confirm
stenosis and gauge its severity.

Treatment
Treatment depends on the symptoms and how
the heart’s function is affected. The valve can be
opened without surgery by using a balloon catheter,
but this is often a temporary solution. The procedure involves inserting a deflated balloon at the end
of a catheter through the arteries to the valve.
Inflating the balloon should widen the valve. In
severe stenosis, heart valve replacement is recommended, most often involving open-heart surgery.
The valve can be replaced with a mechanical valve,
a valve from a pig, or by moving the patient’s other
heart valve (pulmonary) into the position of the
aortic valve and then replacing the pulmonary
valve with an mechanical one. Anyone with aortic
stenosis needs to take antibiotics (amoxicillin, erythromycin, or clindamycin) before dental and some
other surgical procedures, to prevent a heart valve
infection.
370

Cardiac catheterization—A procedure in which
dye is injected through a tube or catheter into an
artery to more easily observe valves or blood vessels seen on an x ray.
Left ventricle—One of the lower chambers of the
heart, which pumps blood to the aorta.
Murmur—An abnormal heart sound that can
reflect a valve dysfunction.
Rheumatic fever—A bacterial infection that often
causes heart inflammation.
Pulmonary valve—The valve located between the
pulmonary artery and the right ventricle, which
brings blood to the lungs.

Prognosis
The prognosis for aortic valve stenosis depends on
the severity of the disease. With surgical repair, the
disease is curable. Patients suffering mild stenosis can
usually lead a normal life; a minority of the patients
progress to severe disease. Anyone with moderate
stenosis should avoid vigorous physical activity.
Most of these patients end up suffering some kind of
coronary heart disease over a 10 year period. Because
it is a progressive disease, moderate and severe stenosis
will be treated ultimately with surgery. Severe disease,
if left untreated, leads to death within 2 to 4 years once
the symptoms start.

Prevention
There is no way to prevent aortic stenosis.
Resources
BOOKS

Bender, Jeffrey R. ‘‘Heart Valve Disease.’’ In Yale University
School of Medicine Heart Book, edited by Barry L.
Zaret, et al. New York: HearstBooks, 1992.
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Aortic Stenosis.’’ Ochsner Heart and VascularInstitute.
<http://www.ochsner.org/pedcard/as.htm>.
Rahimtoola, Aly. ‘‘Aortic Stenosis.’’ Loyola University
Health System Page. <http://www.luhs.org>.

stethoscope to the newborn’s heart and counting
the number of beats.


Grimace, or reflex irritability: 2 if the neonate
coughs, sneezes, or vigorously cries in response to a
stimulus (such as the use of nasal suctioning, stroking
the back to assess for spinal abnormalities, or having
the foot tapped); 1 for a slight cry or grimace in
response to the stimulus; 0 for no response.



Activity, or muscle tone: 2 for vigorous movements
of arms and legs; 1 for some movement; 0 for no
movement, limpness.



Respirations: 2 for visible breathing and crying; 1
for slow, weak, irregular breathing; 0 for apnea,
or no breathing. A crying newborn can adequately oxygenate its lungs. Respirations are best
assessed by watching the rise and fall of the neonate’s abdomen, as infants are diaphragmatic
breathers.

Jeanine Barone, Physiologist

I Apgar testing
Definition
Apgar testing is the assessment of the newborn
rating color, heart rate, stimulus response, muscle
tone, and respirations on a scale of zero to two, for a
maximum possible score of 10. It is performed twice,
first at one minute and then again at five minutes after
birth.

The combined first letters in these five areas spell
Apgar.

Purpose
Apgar scoring was originally developed in the
1950s by the anesthesiologist Virginia Apgar to assist
practitioners attending a birth in deciding whether or
not a newborn was in need of resuscitation. Using a
scoring method fosters consistency and standardization among different practitioners. A February 2001
study published in the New England Journal of
Medicine investigated whether Apgar scoring continues to be relevant. Researchers concluded that
‘‘The Apgar scoring system remains as relevant for
the prediction of neonatal survival today as it was
almost 50 years ago.’’

Description
The five areas are scored as follows:


Appearance, or color: 2 if the skin is pink all over; 1
for acrocyanosis, where the trunk and head are pink,
but the arms and legs are blue; and 0 if the whole
body is blue. Newborns with naturally darker skin
color will not be pink. However, pallor is still noticeable, especially in the soles and palms. Color is
related to the neonate’s ability to oxygenate its
body and extremities, and is dependent on heart
rate and respirations. A perfectly healthy newborn
will often receive a score of 9 because of some blueness in the hands and feet.



Pulse (heart rate): 2 for a pulse of 100+ beats per
minute (bpm); 1 for a pulse below 100 bpm; 0 for no
pulse. Heart rate is assessed by listening with a

GALE ENCYCLOPEDIA OF MEDICINE

Preparation
No preparation is needed to perform the test.
However, while being born the neonate may receive
nasal and oral suctioning to remove mucus and
amniotic fluid. This may be done when the head of
the newborn is safely out, while the mother rests
before she continues to push.

Aftercare
Since the test is primarily observational in nature,
no aftercare is needed. However, the test may flag the
need for immediate intervention or prolonged
observation.

Normal results
The maximum possible score is 10, the minimum
is zero. It is rare to receive a true 10, as some acrocyanosis in the newborn is considered normal, and therefore not a cause for concern. Most infants score
between 7 and 10. These infants are expected to have
an excellent outcome. A score of 4, 5, or 6 requires
immediate intervention, usually in the form of oxygen
and respiratory assistance, or perhaps just suctioning
if breathing has been obstructed by mucus. While
suctioning is being done, a source of oxygen may be
placed near, but not over the newborn’s nose and
mouth. This form of oxygen is referred to as blow-by.
A score in the 4-6 range indicates that the neonate is
having some difficulty adapting to extrauterine life.
371

Apgar testing

OTHER

Apgar testing

D R . V I R G I N I A A P G A R (1909–1974)
in New York during the early 1930s and one of the first
women to graduate from its medical school, Apgar knew
that her goal of becoming a surgeon would not be
achieved easily in a male-dominated profession.
Reluctantly, she switched her medical specialty to anesthesiology, she embraced her new field with typical intelligence and energy. At this time, anesthesiology was a
relatively new field, having been left by the doctors
mostly to the attention of nurses. Apgar realized immediately how much in need of scientifically trained personnel
was this significant part of surgery, and she set out to
make anesthesiology a separate medical discipline. By
1937, she had become the fiftieth physician to be certified
as an anesthesiologist in the United States. The following
year she was appointed director of anesthesiology at the
Columbia-Presbyterian Medical Center, becoming the
first woman to head a department at that institution.

(AP/Wide World Photos. Reproduced by permission.)

As one of very few female medical students at
Columbia University College of Physicians and Surgeons

As the attending anesthesiologist who assisted in the
delivery of thousands of babies during these years, Apgar
realized that infants had died from respiratory or circulatory complications that early treatment could have prevented. Apgar decided to bring her considerable research
skills to this childbirth dilemma, and her careful study
resulted in her publication of the Apgar Score System
in 1952.

Abnormal results

KEY TERMS
Acrocyanosis—A slight cyanosis, or blueness of the
hands and feet of the neonate is considered normal.
This impaired ability to fully oxygenate the extremities is due to an immature circulatory system
which is still in flux.
Amniotic fluid—The protective bag of fluid that
surrounds the fetus while growing in the uterus.
Neonate—A term referring to the newborn infant,
from birth until one month of age.
Neonatologist—A physician who specializes in
problems of newborn infants.
Pallor—Extreme paleness in the color of the skin.

This may be due to medications given to the mother
during a difficult labor, or at the very end of labor,
when these medications have an exaggerated effect on
the neonate.
372

With a score of 0-3, the newborn is unresponsive,
apneic, pale, limp and may not have a pulse.
Interventions to resuscitate will begin immediately.
The test is repeated at five minutes after birth and
both scores are documented. Should the resuscitation
effort continue into the five-minute time period, interventions will not stop in order to perform the test. The
one-minute score indicates the need for intervention at
birth. It addresses survival and prevention of birthrelated complications resulting from inadequate
oxygen supply. Poor oxygenation may be due to
inadequate neurological and/or chemical control of
respiration. The five-minute score appears to have a
more predictive value for morbidity and normal development, although research studies on this are inconsistent in their conclusions.
Resources
BOOKS

Feinbloom, Richard I. Pregnancy, Birth and the EarlyMonths.
Cambridge, MA: Perseus Publishing, 2000.
GALE ENCYCLOPEDIA OF MEDICINE

Aphasia

Pillitteri, Adele. Maternal & Child Nursing; Care ofthe
Childbearing and Childrearing Family. 3rd ed.
Philadelphia: Lippincott, 1999.

Wernicke's area
Broca's area

PERIODICALS

Casey, B. M., D. D. McIntire, and K. J. Leveno. ‘‘The
Continuing Value of Apgar Score for the Assessment of
Newborn Infants’’. NewEngland Journal of Medicine
344 (February 15, 2000): 467-71.
OTHER

Apgar, Virginia. A Proposal for a New Method of Evaluation
of the Newborn Infant. <http://www.apgarfamily.com/
Apgar_Paper.html>.
The National Childbirth Trust. <http://
www.nctpregnancyandbabycare.com>.
PregnancyWeekly.com <http://
www.pregnancyweekly.com>.

Esther Csapo Rastegari, RN, BSN, EdM

I Aphasia
Definition
Aphasia is condition characterized by either partial or total loss of the ability to communicate verbally
or using written words. A person with aphasia may
have difficulty speaking, reading, writing, recognizing
the names of objects, or understanding what other
people have said. Aphasia is caused by a brain injury,
as may occur during a traumatic accident or when
the brain is deprived of oxygen during a stroke. It
may also be caused by a brain tumor, a disease such
as Alzheimer’s, or an infection, like encephalitis.
Aphasia may be temporary or permanent. Aphasia
does not include speech impediments caused by loss
of muscle control.

Description
To understand and use language effectively, an
individual draws upon word memory–stored information on what certain words mean, how to put them
together, and how and when to use them properly. For
a majority of people, these and other language functions are located in the left side (hemisphere) of the
brain. Damage to this side of the brain is most commonly linked to the development of aphasia.
Interestingly, however, left-handed people appear to
have language areas in both the left and right hemispheres of the brain and, as a result, may develop
aphasia from damage to either side of the brain.
GALE ENCYCLOPEDIA OF MEDICINE

Broca’s aphasia results from damage to the frontal lobe of the
language-dominant area of the brain. Individuals with
Broca’s aphasia may become mute or may be able to use
single-word statements or full sentences, although it may
require great effort. Wernicke’s aphasia is caused by damage
to the temporal lobe of the language-dominant area of the
brain. People with this condition speak in long, uninterrupted
sentences, but the words used are often unnecessary and
unintelligible. (Illustration by Electronic Illustrators Group.)

Stroke is the most common cause of aphasia in the
United States. Approximately 500,000 individuals suffer strokes each year, and 20% of these individuals
develop some type of aphasia. Other causes of brain
damage include head injuries, brain tumors, and infection. About half of the people who show signs of aphasia have what is called temporary or transient aphasia
and recover completely within a few days. An estimated
one million Americans suffer from some form of permanent aphasia. As yet, no connection between aphasia
and age, gender, or race has been found.
Aphasia is sometimes confused with other conditions that affect speech, such as dysarthria and
apraxia. These condition affect the muscles used in
speaking rather than language function itself.
Dysarthria is a speech disturbance caused by lack of
control over the muscles used in speaking, perhaps due
to nerve damage. Speech apraxia is a speech disturbance in which language comprehension and muscle
control are retained, but the memory of how to use the
muscles to form words is not.
373

Aphasia

KEY TERMS
Anomic aphasia—A condition characterized by
either partial or total loss of the ability to recall the
names of persons or things as a result of a stroke,
head injury, brain tumor, or infection.
Broca’s aphasia—A condition characterized by either
partial or total loss of the ability to express oneself,
either through speech or writing. Hearing comprehension is not affected. This condition may result from a
stroke, head injury, brain tumor, or infection.
Computed tomography (CT)—An imaging technique that uses cross-sectional x rays of the body to
create a three-dimensional image of the body’s internal structures.
Conduction aphasia—A condition characterized by
the inability to repeat words, sentences, or phrases as
a result of a stroke, head injury, brain tumor, or
infection.
Frontal lobe—The largest, most forward-facing part
of each side or hemisphere of the brain.
Global aphasia—A condition characterized by either
partial or total loss of the ability to communicate verbally or using written words as a result of widespread
injury to the language areas of the brain. This condition
may be caused by a stroke, head injury, brain tumor,
or infection. The exact language abilities affected vary
depending on the location and extent of injury.

Causes and symptoms
Aphasia can develop after an individual sustains
a brain injury from a stroke, head trauma, tumor, or
infection, such as herpes encephalitis. As a result of
this injury, the pathways for language comprehension or production are disrupted or destroyed. For
most people, this means damage to the left hemisphere of the brain. (In 95 to 99% of right-handed
people, language centers are in the left hemisphere,
and up to 70% of left-handed people also have lefthemisphere language dominance.) According to the
traditional classification scheme, each form of
aphasia is caused by damage to a different part of
the left hemisphere of the brain. This damage affects
one or more of the basic language functions: speech,
naming (the ability to identify an object, color, or
other item with an appropriate word or term), repetition (the ability to repeat words, phrases, and sentences), hearing comprehension (the ability to
374

Hemisphere—One of the two halves or sides-the left
and the right-of the brain.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Subcortical aphasia—A condition characterized by
either partial or total loss of the ability to communicate verbally or using written words as a result of
damage to non language-dominated areas of the
brain. This condition may be caused by a stroke,
head injury, brain tumor, or infection.
Temporal lobe—The part of each side or hemisphere
of the brain that is on the side of the head, nearest the
ears.
Transcortical aphasia—A condition characterized
by either partial or total loss of the ability to communicate verbally or using written words that does not
affect an individual’s ability to repeat words,
phrases, and sentences.
Wernicke’s aphasia—A condition characterized by
either partial or total loss of the ability to understand
what is being said or read. The individual maintains
the ability to speak, but speech may contain unnecessary or made-up words.

understand spoken language), reading (the ability
to understand written words and their meaning),
and writing (the ability to communicate and record
events with text).
The traditional classification scheme includes
eight types of aphasia:


Broca’s aphasia, also called motor aphasia, results
from damage to the front portion or frontal lobe of
the language-dominant area of the brain. Individuals
with Broca’s aphasia may be completely unable to
use speech (mutism) or may be able to use singleword statements or even full sentences, though
these sentences may require a great deal of effort to
construct. Small words, such as conjunctions (and,
or, but) and articles (the, an, a), may be omitted,
leading to a ‘‘telegraph’’ quality in their speech.
Hearing comprehension is usually not affected, so
they are able to understand other people’s speech
and conversation and can follow commands. Often,
GALE ENCYCLOPEDIA OF MEDICINE



Wernicke’s aphasia is caused by damage to the side
portion or temporal lobe of the language-dominant
area of the brain. Individuals with Wernicke’s aphasia speak in long, uninterrupted sentences; however,
the words used are frequently unnecessary or even
made-up. They have a great deal of difficulty understanding other people’s speech, sometimes to the
point of being unable to understand spoken language
at all. Reading ability is diminished, and although
writing ability is retained, what is written may be
abnormal. No physical symptoms, such as the
right-sided weakness seen with Broca’s aphasia, are
typically observed. Also, in contrast to Broca’s aphasia, individuals with Wernicke’s aphasia are not
aware of their language errors.



Global aphasia is caused by widespread damage to
the language areas of the left hemisphere. As a result,
all basic language functions are affected, but some
areas may be more affected than others. For example, an individual may have difficulty speaking but
may be able to write well. The individual may experience weakness and loss of feeling on the right side of
their body.



Conduction aphasia, also called associative aphasia,
is rather uncommon. Individuals with conduction
aphasia are unable to repeat words, sentences, and
phrases. Speech is fairly unbroken, although individuals may frequently correct themselves and words
may be skipped or repeated. Although able to understand spoken language, it may also be difficult for the
individual with conduction aphasia to find the right
word to describe a person or object. The impact of
this condition on reading and writing ability varies.
As with other types of aphasia, right-sided weakness
or sensory loss may be present.



Anomic or nominal aphasia primarily influences an
individual’s ability to find the right name for a person or object. As a result, an object may be described
rather than named. Hearing comprehension, repetition, reading, and writing are not affected, other than
by this inability to find the right name. Speech is
fluent, except for pauses as the individual tries to
recall the right name. Physical symptoms are variable, and some individuals have no symptoms of onesided weakness or sensory loss.

GALE ENCYCLOPEDIA OF MEDICINE



Transcortical aphasia is caused by damage to the
language areas of the left hemisphere outside the
primary language areas. There are three types of
aphasia: transcortical motor aphasia, transcortical
sensory aphasia, and mixed transcortical aphasia.
All of the transcortical aphasias are distinguished
from other types by the individual’s ability to repeat
words, phrases, or sentences. Other language functions may also be impaired to varying degrees,
depending on the extent and particular location of
brain damage.

As researchers continue to learn more about the
brain’s structure and function, new types of aphasia
are being recognized. One newly recognized type of
aphasia, subcortical aphasia, mimics the symptoms
of other traditional types of aphasia but involves
language disorders that are not typical. This type of
aphasia is associated with injuries to areas of the brain
typically not identified with language and language
processing.

Diagnosis
Following brain injury, an initial bedside assessment is made to determine whether language function has been affected. If the individual experiences
difficulty communicating, attempts are made to
determine whether this difficulty arises from
impaired language comprehension or an impaired
ability to speak. A typical examination involves
listening to spontaneous speech and evaluating the
individual’s ability to recognize and name objects,
comprehend what is heard, and repeat sample words
and phrases. The individual may also be asked to
read text aloud and explain what the passage
means. In addition, writing ability is evaluated by
having the individual copy text, transcribe dictated
text, and write something without prompting.
A speech pathologist or neuropsychologist may
be asked to conduct more extensive examinations
using in-depth, standardized tests. Commonly used
tests include the Boston Diagnostic Aphasia
Examination, the Western Aphasia Battery, and possibly, the Porch Index of Speech Ability.
The results of these tests indicate the severity of
the aphasia and may also provide information regarding the exact location of the brain damage. This more
extensive testing is also designed to provide the information necessary to design an individualized speech
therapy program. Further information about the location of the damage is gained through the use of imaging technology, such as magnetic resonance imaging
(MRI) and computed tomography scans (CT).
375

Aphasia

they may experience weakness on the right side of
their bodies, which can make it difficult to write.
Reading ability is impaired, and they may have difficulty finding the right word when speaking.
Individuals with Broca’s aphasia may become frustrated and depressed because they are aware of their
language difficulties.

Aplastic anemia

Treatment
Initially, the underlying cause of aphasia must be
treated or stabilized. To regain language function,
therapy must begin as soon as possible following the
injury. Although there are no medical or surgical procedures currently available to treat this condition,
aphasia resulting from stroke or head injury may
improve through the use of speech therapy. For most
individuals, however, the primary emphasis is placed
on making the most of retained language abilities and
learning to use other means of communication to
compensate for lost language abilities.
Speech therapy is tailored to meet individual
needs, but activities and tools that are frequently
used include the following:




Exercise and practice. Weakened muscles are exercised by repetitively speaking certain words or making facial expressions, such as smiling.

Prevention
Because there is no way of knowing when a
stroke, traumatic head injury, or disease will occur,
very little can be done to prevent aphasia. The extent
of recovery, however, in some cases, can be affected
by an individual’s willingness to cooperate and participate in speech therapy directly following the injury.
Resources
BOOKS

Lyon, Jon G., and Marianne B. Simpson. Coping with
Aphasia. San Diego: Singular Publishing Group, 1998.
ORGANIZATIONS

National Aphasia Association. 156 5th Ave., Suite 707, New
York, NY 10010. (800) 922-4622. <http://
www.aphasia.org>.

Picture cards. Pictures of everyday objects are used
to improve word recall and increase vocabulary. The
names of the objects may also be repetitively spoken
aloud as part of an exercise and practice routine.



Picture boards. Pictures of everyday objects and
activities are placed together, and the individual
points to certain pictures to convey ideas and communicate with others.



Workbooks. Reading and writing exercises are used
to sharpen word recall and regain reading and writing abilities. Hearing comprehension is also redeveloped using these exercises.



and the start of therapy may also affect the eventual
outcome.

Computers. Computer software can be used to
improve speech, reading, recall, and hearing comprehension by, for example, displaying pictures and
having the individual find the right word.

Prognosis
The degree to which an individual can recover
language abilities is highly dependent on how much
brain damage occurred and the location and cause of
the original brain injury. Other factors include the
individual’s age, general health, motivation and willingness to participate in speech therapy, and whether
the individual is left or right handed. Language areas
may be located in both the left and right hemispheres
in left-handed individuals. Left-handed individuals
are, therefore, more likely to develop aphasia following brain injury, but because they have two language
centers, may recover more fully because language abilities can be recovered from either side of the brain. The
intensity of therapy and the time between diagnosis
376

Julia Barrett

Apheres see Transfusion

I Aplastic anemia
Definition
Aplastic anemia is a disorder in which the bone
marrow greatly decreases or stops production of
blood cells.

Description
The bone marrow (soft tissue that is located
within the hard outer shell of the bones) is responsible
for the production of all types of blood cells. The
mature forms of these cells include red blood cells,
which carry oxygen throughout the body; white
blood cells, which fight infection; and platelets,
which are involved in clotting. In aplastic anemia,
the basic structure of the marrow becomes abnormal,
and those cells responsible for generating blood cells
(hematopoietic cells) are greatly decreased in number
or absent. These hematopoietic cells are replaced by
large quantities of fat.
Yearly, aplastic anemia strikes about 5-10 people
in every one million. Although aplastic anemia strikes
both males and females of all ages, there are two age
groups that have an increased risk. Both young adults
GALE ENCYCLOPEDIA OF MEDICINE

Bone marrow—A substance found in the cavities of
bones, especially the long bones and the sternum
(breast bone). The bone marrow contains those cells
that are responsible for the production of the blood
cells (red blood cells, white blood cells, and platelets).
Bone marrow transplant—A procedure in which a
quantity of bone marrow is extracted through a needle from a donor, and then passed into a patient to
replace the patient’s diseased or absent bone marrow.
Hematopoietic cells—Those cells that are lodged
within the bone marrow, and which are responsible
for producing the cells which circulate in the blood
(red blood cells, white blood cells, and platelets).

(between 15-30 years of age) and the elderly (over the
age of 60) have higher rates of aplastic anemia than the
general population. While the disorder occurs worldwide, young adults in Asia have a higher disease rate
than do populations in North America and Europe.

Causes and symptoms
Aplastic anemia falls into three basic categories,
based on the origin of its cause: idiopathic, acquired,
and hereditary.
In about 60% of cases, aplastic anemia is considered to be idiopathic, meaning that the cause of the
disorder is unknown.
Acquired aplastic anemia refers to those cases
where certain environmental factors and physical conditions seem to be associated with development of the
disease. Acquired aplastic anemia can be associated
with:


exposure to drugs, especially anti-cancer agents,
antibiotics, anti-inflammatory agents, seizure
medications, and antithyroid drugs (drugs given to
stop the functioning of an overactive thyroid)



exposure to radiation



chemical exposure (especially to the organic solvent
benzene and certain insecticides)



infection with certain viruses (especially those causing viral hepatitis, as well as Epstein-Barr virus, parvovirus, and HIV, the virus that can cause AIDS)



pregnancy



certain other disorders, including a disease called paroxysmal nocturnal hemoglobinuria, an autoimmune

GALE ENCYCLOPEDIA OF MEDICINE

reaction called graft-vs-host disease (which occurs
when the body’s immune system attacks and destroys
the body’s own cells), and certain connective tissue
diseases
Hereditary aplastic anemia is relatively rare, but
occurs in Fanconi’s anemia, Shwachman-Diamond
syndrome, and dyskeratosis congenita.
Symptoms of aplastic anemia tend to be those of
other anemias, including fatigue, weakness, tiny reddish-purple marks (petechiae) on the skin (evidence of
pinpoint hemorrhages into the skin), evidence of abnormal bruising, and bleeding from the gums, nose, intestine, or vagina. The patient is likely to appear pale. If
the anemia progresses, decreased oxygen circulating in
the blood may lead to an increase in heart rate and the
sudden appearance of a new heart murmur.

Diagnosis
The blood count in aplastic anemia will reveal low
numbers of all formed blood cells. Red blood cells will
appear normal in size and coloration, but greatly
decreased in number. Cells called reticulocytes (very
young red blood cells, which are usually produced in
great numbers by the bone marrow in order to compensate for a severe anemia) will be very low in number. Platelets and white blood cells will also be
decreased in number, though normal in structure.
A sample of the patient’s bone marrow will need
to be removed by needle (usually from the hip bone)
and examined under a microscope. If aplastic anemia
is present, this examination will reveal very few or no
hematopoietic cells, and replacement with fat.

Treatment
The first step in the treatment of aplastic anemia
involves discontinuing exposure to any substance that
may be causing the disorder. Although it would seem
that blood transfusions would be helpful in this disease, in fact, they only serve as a temporary help, and
may complicate future attempts at bone marrow
transplantation.
The most successful treatment for aplastic anemia
is bone marrow transplantation. To do this, a marrow
donor (often a sibling) must be identified. There are a
number of tissue markers that must be examined to
determine whether a bone marrow donation is likely to
be compatible with the patient’s immune system.
Compatibility is necessary to avoid complications,
including the destruction of the donor marrow by the
patient’s own immune system.

377

Aplastic anemia

KEY TERMS

Appendectomy

Patients who cannot undergo bone marrow
transplant can be treated with a number of agents,
including antithymocyte globulin (ATG), cyclophosphamide, steroids, and cyclosporine. These agents
all have the potential to cause a number of troublesome side-effects and may have a success rate of only
60% to 80%. Still, even among those patients who
have a good response, many later suffer a relapse
(return) of aplastic anemia. Researchers are trying to
identify the molecules in certain stem cells that the
immune system targets in aplastic anemia.

Prognosis
Aplastic anemia is a life-threatening illness.
Without treatment, it will almost surely progress to
death. Survival depends on how severe the disease is at
diagnosis, which type of treatment a patient is eligible
for, and what kind of response their body has to that
treatment. The worst-prognosis type of aplastic anemia
is one associated with very low numbers of a particular
type of white blood cell. These patients have a high
chance of dying from overwhelming bacterial infections. In fact, 80% of all patients treated with blood
transfusions alone die within 18 months to two years.
Patients who undergo bone marrow transplantation
have a 60-90% chance of being cured of the disease.
Resources
PERIODICALS

Marsh, Judith C.W., Edward C. Gordon-Smith. ‘‘Insights
Into the Autoimmune Nature of Aplastic Anemia.’’ The
Lancet (July 24, 2004): 308.
ORGANIZATIONS

Appendectomies are performed to treat appendicitis, an inflamed and infected appendix.

Precautions
Since appendicitis occurs most commonly in
males between the ages of 10-14 and in females
between the ages of 15-19, appendectomy is most
often performed during this time. The diagnosis of
appendicitis is most difficult in the very young (less
than two years of age) and in the elderly.

Description
Appendectomy is considered a major surgical
operation. Therefore, a general surgeon must perform
this operation in the operating room of a hospital. An
anesthesiologist is also present during the operation to
administer an anesthetic. Most often the anesthesiologist uses a general anesthetic technique whereby
patients are put to sleep and made pain free by
administering drugs in the vein or by agents inhaled
through a tube placed in the windpipe. Occasionally a
spinal anesthetic may be used.
After the patient is anesthetized, the general
surgeon can remove the appendix either by using
the traditional open procedure (in which a 2-3 in
[5-7.6 cm] incision is made in the abdomen) or via
laparoscopy (in which four 1 in [2.5cm] incisions are
made in the abdomen).
Traditional open appendectomy

Aplastic Anemia Foundation of America. P.O. Box 613,
Annapolis, MD 21404. (800) 747-2820. <http://
www.aplastic.org>.

Rosalyn Carson-DeWitt, MD
Teresa G. Odle

Aplastic crisis see Fifth disease

I Appendectomy
Definition
Appendectomy is the surgical removal of the
appendix. The appendix is a worm-shaped hollow
pouch attached to the cecum, the beginning of the
large intestine.
378

Purpose

When the surgeon uses the open approach, he
makes an incision in the lower right section of the
abdomen. Most incisions are less than 3 in (7.6 cm)
in length. The surgeon then identifies all of the organs
in the abdomen and examines them for other disease
or abnormalities. The appendix is located and brought
up into the wounds. The surgeon separates the appendix from all the surrounding tissue and its attachment
to the cecum and then removes it. The site where the
appendix was previously attached, the cecum, is closed
and returned to the abdomen. The muscle layers and
then the skin are sewn together.
Laproscopic appendectomy
When the surgeon conducts a laproscopic appendectomy, four incisions, each about 1 in (2.5 cm) in
length, are made. One incision is near the umbilicus, or
navel, and one is between the umbilicus and the pubis.
Two other incisions are smaller and are in the right
GALE ENCYCLOPEDIA OF MEDICINE

Appendectomy

Large intestine

Appendix

Rectum

Cecum

Swollen and
inflamed appendix
Cecum
A traditional open appendectomy. After the surgeon makes an incision in the lower right section of the abdomen, he/she pulls
the appendix up, separates it from the surrounding tissue and its attachment to the cecum, and then removes it. (Illustration by
Electronic Illustrators Group.)

side of the lower abdomen. The surgeon then passes a
camera and special instruments through these incisions. With the aid of this equipment, the surgeon
visually examines the abdominal organs and identifies
the appendix. Similarly, the appendix is freed from
all of its attachments and removed. The place where
the appendix was formerly attached, the cecum, is
stitched. The appendix is removed through one of the
incisions. The instruments are removed and then all of
the incisions are closed.
Studies and opinions about the relative advantages and disadvantages of each method are divided.
A skilled surgeon can perform either one of these
procedures in less than one hour. However, laproscopic appendectomy (LA) always takes longer than
traditional appendectomy (TA). The increased time
required to do a LA increases the patient’s exposure
GALE ENCYCLOPEDIA OF MEDICINE

to anesthetics, which increases the risk of complications. The increased time requirement also escalates
fees charged by the hospital for operating room time
and by the anesthesiologist. Since LA also requires
specialized equipment, the fees for its use also
increases the hospital charges. Patients with either
operation have similar pain medication needs, begin
eating diets at comparable times, and stay in the hospital equivalent amounts of time. LA is of special
benefit in women in whom the diagnosis is difficult
and gynecological disease (such as endometriosis, pelvic inflammatory disease, ruptured ovarian follicles,
ruptured ovarian cysts, and tubal pregnancies) may be
the source of pain and not appendicitis. If LA is done
in these patients, the pelvic organs can be more thoroughly examined and a definitive diagnosis made prior
to removal of the appendix. Most surgeons select
379

Appendectomy

KEY TERMS
Abscess—A collection of pus buried deep in the
tissues or in a body cavity.
Anesthesiologist—A physician who has special
training and expertise in the delivery of anesthetics.
Anesthetics—Drugs or methodologies used to
make a body area free of sensation or pain.
Cecum—The beginning of the large intestine and
the place where the appendix attaches to the intestinal tract.
General surgeon—A physician who has special
training and expertise in performing a variety of
operations.
Pelvic organs— The organs inside of the body that
are located within the confines of the pelvis. This
includes the bladder and rectum in both sexes and
the uterus, ovaries, and fallopian tubes in females.
Pubis—The anterior portion of the pelvis located in
the anterior abdomen.
Thrombophlebitis—Inflammation of the veins,
usually in the legs, which causes swelling and tenderness in the affected area.
Umbilicus—The navel.

either TA or LA based on the individual needs and
circumstances of the patient.
Insurance plans do cover the costs of appendectomy. Fees are charged independently by the hospital
and the physicians. Hospital charges include fees for
operating and recovery room use, diagnostic and
laboratory testing, as well as the normal hospital
room charges. Surgical fees vary from region to region
and range between $250-$750. The anesthesiologist’s
fee depends upon the health of the patient and the
length of the operation.

Preparation
Once the diagnosis of appendicitis is made and the
decision has been made to perform an appendectomy,
the patient undergoes the standard preparation for an
operation. This usually takes only one to two hours
and includes signing the operative consents, patient
identification procedures, evaluation by the anesthesiologist, and moving the patient to the operating suites
of the hospital. Occasionally, if the patient has been ill
for a prolonged period of time or has had protracted
380

vomiting, a delay of few to several hours may be necessary to give the patient fluids and antibiotics.

Aftercare
Recovery from an appendectomy is similar to
other operations. Patients are allowed to eat when
the stomach and intestines begin to function again.
Usually the first meal is a clear liquid diet–broth,
juice, soda pop, and gelatin. If patients tolerate this
meal, the next meal usually is a regular diet. Patients
are asked to walk and resume their normal physical
activities as soon as possible. If TA was done, work
and physical education classes may be restricted for a
full three weeks after the operation. If a LA was done,
most patients are able to return to work and strenuous
activity within one to three weeks after the operation.

Risks
Certain risks are present when any operation
requires a general anesthetic and the abdominal cavity
is opened. Pneumonia and collapse of the small airways (atelectasis) often occurs. Patients who smoke
are at a greater risk for developing these complications. Thrombophlebitis, or inflammation of the
veins, is rare but can occur if the patient requires
prolonged bed rest. Bleeding can occur but rarely is a
blood transfusion required. Adhesions (abnormal connections to abdominal organs by thin fibrous tissue) is
a known complication of any abdominal procedure
such as appendectomy. These adhesions can lead to
intestinal obstruction which prevents the normal flow
of intestinal contents. Hernia is a complication of any
incision, However, they are rarely seen after appendectomy because the abdominal wall is very strong in
the area of the standard appendectomy incision.
The overall complication rate of appendectomy
depends upon the status of the appendix at the time
it is removed. If the appendix has not ruptured the
complication rate is only about 3%. However, if the
appendix has ruptured the complication rate rises to
almost 59%. Wound infections do occur and are more
common if the appendicitis was severe, far advanced,
or ruptured. An abscess may form in the abdomen as a
complication of appendicitis.
Occasionally, an appendix will rupture prior to its
removal, spilling its contents into the abdominal cavity.
Peritonitis or a generalized infection in the abdomen
will occur. Treatment of peritonitis as a result of a
ruptured appendix includes removal of what remains
of the appendix, insertion of drains (rubber tubes that
promote the flow of infection inside the abdomen to
GALE ENCYCLOPEDIA OF MEDICINE

Appendicitis

outside of the body), and antibiotics. Fistula formation
(an abnormal connection between the cecum and the
skin) rarely occurs. It is only seen if the appendix has a
broad attachment to the cecum and the appendicitis is
far advanced causing destruction of the cecum itself.

Normal results
Most patients feel better immediately after an
operation for appendicitis. Many patients are discharged from the hospital within 24 hours after the
appendectomy. Others may require a longer stay–
three to five days. Almost all patients are back to
their normal activities within three weeks.
The mortality rate of appendicitis has dramatically
decreased over time. Currently, the mortality rate is
estimated at one to two per 1,000,000 cases of appendicitis. Death is usually due to peritonitis, intra abdominal abscess or severe infection following rupture.
The complications associated with undiagnosed,
misdiagnosised, or delayed diagnosis of appendectomy are very significant. The diagnosis is of appendicitis is difficult and never certain. This has led surgeons
to perform an appendectomy any time that they feel
appendicitis is the diagnosis. Most surgeons feel that
in approximately 20% of their patients, a normal
appendix will be removed. Rates much lower than
this would seem to indicate that the diagnosis of
appendicitis was being frequently missed.
Resources
PERIODICALS

McCall, J. L., K. Sharples, and F. Jafallah. ‘‘Systematic
Review of Randomized Controlled Trial Comparing
Laproscopic with Open Appendectomy.’’British
Journal of Surgery 84, no. 8 (August 1997): 1045-1950.
OTHER

‘‘Appendectomy.’’ ThriveOnline. <http://
thriveonline.oxygen.com>.
‘‘The Appendix.’’ Mayo Clinic Online. <http://
www.mayohealth.org>.

Mary Jeanne Krob, MD, FACS

I Appendicitis
Definition
Appendicitis is an inflammation of the appendix,
which is the worm-shaped pouch attached to the
GALE ENCYCLOPEDIA OF MEDICINE

An extracted appendix. (Photograph by Lester V. Bergman,
Corbis Images. Reproduced by permission.)

cecum, the beginning of the large intestine. The appendix has no known function in the body, but it can
become diseased. Appendicitis is a medical emergency,
and if it is left untreated the appendix may rupture and
cause a potentially fatal infection.

Description
Appendicitis is the most common abdominal
emergency found in children and young adults. One
person in 15 develops appendicitis in his or her lifetime. The incidence is highest among males aged
10-14, and among females aged 15-19. More males
than females develop appendicitis between puberty
and age 25. It is rare in the elderly and in children
under the age of two.
The hallmark symptom of appendicitis is increasingly severe abdominal pain. Since many different conditions can cause abdominal pain, an accurate
diagnosis of appendicitis can be difficult. A timely
diagnosis is important, however, because a delay can
result in perforation, or rupture, of the appendix.
When this happens, the infected contents of the appendix spill into the abdomen, potentially causing a serious infection of the abdomen called peritonitis.
381

Appendicitis

KEY TERMS
Appendectomy (or appendicectomy)—Surgical
removal of the appendix.
Appendix—The worm-shaped pouch attached to
the cecum, the beginning of the large intestine.
Laparotomy—Surgical incision into the loin,
between the ribs and the pelvis, which offers surgeons a view inside the abdominal cavity.
Peritonitis—Inflammation of the peritoneum,
membranes lining the abdominal pelvic wall.

Other conditions can have similar symptoms,
especially in women. These include pelvic inflammatory disease, ruptured ovarian follicles, ruptured ovarian cysts, tubal pregnancies, and endometriosis.
Various forms of stomach upset and bowel inflammation may also mimic appendicitis.
The treatment for acute (sudden, severe) appendicitis is an appendectomy, surgery to remove the appendix. Because of the potential for a life-threatening
ruptured appendix, persons suspected of having
appendicitis are often taken to surgery before the
diagnosis is certain.

Causes and symptoms
The causes of appendicitis are not well understood, but it is believed to occur as a result of one or
more of these factors: an obstruction within the
appendix, the development of an ulceration (an abnormal change in tissue accompanied by the death of
cells) within the appendix, and the invasion of
bacteria.
Under these conditions, bacteria may multiply
within the appendix. The appendix may become swollen and filled with pus (a fluid formed in infected tissue,
consisting of while blood cells and cellular debris), and
may eventually rupture. Signs of rupture include the
presence of symptoms for more than 24 hours, a fever, a
high white blood cell count, and a fast heart rate. Very
rarely, the inflammation and symptoms of appendicitis
may disappear but recur again later.
The distinguishing symptom of appendicitis is
pain beginning around or above the navel. The pain,
which may be severe or only achy and uncomfortable,
eventually moves into the right lower corner of the
abdomen. There, it becomes more steady and more
severe, and often increases with movement, coughing,
382

and so forth. The abdomen often becomes rigid and
tender to the touch. Increasing rigidity and tenderness
indicates an increased likelihood of perforation and
peritonitis.
Loss of appetite is very common. Nausea and
vomiting may occur in about half of the cases and
occasionally there may be constipation or diarrhea.
The temperature may be normal or slightly elevated.
The presence of a fever may indicate that the appendix
has ruptured.

Diagnosis
A careful examination is the best way to diagnose appendicitis. It is often difficult even for
experienced physicians to distinguish the symptoms
of appendicitis from those of other abdominal disorders. Therefore, very specific questioning and a
thorough physical examination are crucial. The
physician should ask questions, such as where the
pain is centered, whether the pain has shifted, and
where the pain began. The physician should press
on the abdomen to judge the location of the pain
and the degree of tenderness.
The typical sequence of symptoms is present in
about 50% of cases. In the other half of cases, less
typical patterns may be seen, especially in pregnant
women, older patients, and infants. In pregnant
women, appendicitis is easily masked by the frequent occurrence of mild abdominal pain and
nausea from other causes. Elderly patients may
feel less pain and tenderness than most patients,
thereby delaying diagnosis and treatment, and
leading to rupture in 30% of cases. Infants and
young children often have diarrhea, vomiting,
and fever in addition to pain.
While laboratory tests cannot establish the diagnosis, an increased white cell count may point to
appendicitis. Urinalysis may help to rule out a urinary
tract infection that can mimic appendicitis.
Patients whose symptoms and physical examination are compatible with a diagnosis of appendicitis
are usually taken immediately to surgery, where a
laparotomy (surgical exploration of the abdomen) is
done to confirm the diagnosis. In cases with a questionable diagnosis, other tests, such as a computed
tomography scan (CT) may be performed to avoid
unnecessary surgery. An ultrasound examination of
the abdomen may help to identify an inflamed appendix or other condition that would explain the symptoms. Abdominal x-rays are not of much value except
when the appendix has ruptured.
GALE ENCYCLOPEDIA OF MEDICINE

When appendicitis is strongly suspected in a
woman of child-bearing age, a diagnostic laparoscopy
(an examination of the interior of the abdomen) is
sometimes recommended before the appendectomy in
order to be sure that a gynecological problem, such as a
ruptured ovarian cyst, is not causing the pain. In this
procedure, a lighted viewing tube is inserted into the
abdomen through a small incision around the navel.
A normal appendix is discovered in about 10-20%
of patients who undergo laparotomy, because of suspected appendicitis. Sometimes the surgeon will
remove a normal appendix as a safeguard against
appendicitis in the future. During the surgery, another
specific cause for the pain and symptoms of appendicitis is found for about 30% of these patients.

Treatment
The treatment of appendicitis is an immediate
appendectomy. This may be done by opening the abdomen in the standard open appendectomy technique, or
through laparoscopy. In laparoscopy, a smaller incision
is made through the navel. Both methods can successfully accomplish the removal of the appendix. It is not
certain that laparoscopy holds any advantage over open
appendectomy. When the appendix has ruptured,
patients undergoing a laparoscopic appendectomy may
have to be switched to the open appendectomy procedure for the successful management of the rupture. If a
ruptured appendix is left untreated, the condition is fatal.

Prognosis
Appendicitis is usually treated successfully by
appendectomy. Unless there are complications, the
patient should recover without further problems. The
mortality rate in cases without complications is less
than 0.1%. When an appendix has ruptured, or a
severe infection has developed, the likelihood is higher
for complications, with slower recovery, or death from
disease. There are higher rates of perforation and
mortality among children and the elderly.

Prevention
Appendicitis is probably not preventable, although
there is some indication that a diet high in green vegetables and tomatoes may help prevent appendicitis.
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

Van Der Meer, Antonia. ‘‘Do You Know the Warning Signs
of Appendicitis?’’ Parents Magazine (April 1997): 49.

Caroline A. Helwick

Appendix removal see Appendectomy

I Appetite-enhancing drugs
Definition
Appetite-enhancing drugs are a diverse group of
medications given to prevent undesired weight loss in
the elderly and in patients suffering from such diseases
as AIDS and cancer, which often result in wasting of
the body’s muscle tissue as well as overall weight loss.
The medical term for these drugs is orexigenic, which
is derived from the Greek word for ‘‘appetite’’ or
‘‘desire.’’ None of the orexigenic drugs in common
use as of 2005, however, were originally formulated
or prescribed as appetite stimulants; they range from
antihistamines and antiemetics (drugs given to treat or
prevent nausea and vomiting) to antidepressants and
synthetic hormones. The medications most often used
in the early 2000s include mirtazapine (Remeron), a
tetracyclic antidepressant; cyproheptadine (Periactin),
an antihistamine; dronabinol (Marinol, THC), an
antiemetic; nandrolone, oxymetholone, and oxandrolone (Anadrol-50, Durabolin, Hybolin, Oxandrin, and
other brand nam! es), which are anabolic steroids
related to the male sex hormone testosterone; and
megestrol acetate (Megace), a synthetic derivative of
the female sex hormone progesterone. In addition to
these prescription drugs, fish oil (eicosapentaenoic acid
or EPA) has been recommended as an alternative
or complementary treatment for undesired weight loss.

Purpose
The reader should note the distinction between
appetite and hunger in order to understand why a
group of such different medications could be used to
stimulate the desire for food. Hunger is defined as the
body’s basic physical need for food, whether in terms
of calorie content or specific nutrients. Appetite, on
the other hand, refers to the complex desires in
humans for food and drink that are often conditioned
or influenced by previous experiences or cultural factors as well as by a person’s present health status.
383

Appetite-enhancing drugs

Often, the diagnosis is not certain until an operation is done. To avoid a ruptured appendix, surgery
may be recommended without delay if the symptoms
point clearly to appendicitis. If the symptoms are not
clear, surgery may be postponed until they progress
enough to confirm a diagnosis.

Appetite-enhancing drugs

People may have an appetite for food in the absence of
hunger; conversely, they may be hungry in the physical
sense but have little or no appetite. Loss of appetite
may lead to a type of malnutrition known as undernutrition, which is characterized by food intake that
falls below a recommended daily allowance of calories
or by the body’s inability to make use of the nutrients
in the food that is consumed.
People may become anorexic (lose their appetite
for food) for a variety of physical, emotional, and
social reasons:


Sensory changes related to aging. Elderly persons
often experience a partial loss of the senses of taste
and smell, which means that they may not enjoy their
meals as much as they did when they were younger.
In addition, many elderly persons feel full after eating relatively small amounts of food. It is thought
that this early feeling of fullness is caused by
increased secretion of gastric hormones known as
cholecystokinins.



Gastrointestinal disorders. Patients with such disorders as Crohn’s disease or gastric atonia (abnormally
slow emptying of the stomach) may lose their appetite for food.



Severe diseases that affect the entire body, particularly cancer and AIDS. Patients with these diseases
may develop cachexia, a potentially life-threatening
condition characterized by unintended weight loss
and wasting of lean muscle tissue. Cachexia is often
accompanied by loss of appetite.



Medication side effects. In addition to the drugs used
in cancer chemotherapy, such drugs as fluoxetine
(Prozac), digoxin (Lanoxin), quinidine (Duraquin,
Cardioquin), hydralazine (Alazine, Apresoline), certain antibiotics, and vitamin A may cause loss of
appetite.



Emotional stress. Many people do not feel like eating
before examinations, job interviews, public speaking,
artistic performances, athletic competitions, or similar stressful situations.



Depression and other mood disorders. Loss of appetite is a common feature of depressive episodes as
well as of major depressive disorder.



Cultural factors. The types of food that people find
appetizing are influenced by their respective cultures;
for example, Westerners usually find the use of cats
and dogs for food in China and Korea upsetting or
disgusting because they regard these animals as
domestic pets rather than dietary items. In addition,
many people lose their appetite when they discover
insects, hair, or other evidence of unsanitary

384

conditions in their food, or when they find that a
dish’s ingredients violate the dietary laws of their
religion.


Social isolation. Research indicates that human
appetite for food is stimulated by eating in the company of others. Loss of appetite in many elderly
people is associated with living alone.



Previous experience. People who have developed
food poisoning after eating contaminated or improperly refrigerated salads, raw clams or oysters, or
similar foods may develop a long-term distaste for
the food that made them sick.

Given the complexity and variety of factors that
influence the desire for food in humans, doctors often
use such questionnaires as the Mini Nutritional
Assessment or the Nutrition Screening Index before
prescribing any appetite-enhancing drug. Many
patients can be successfully treated by changes in the
type or dosage of medications they are taking for
other conditions, or by therapy directed at an underlying mood disorder or gastrointestinal disease.
Others can be helped by changes in their living situations that allow them to share mealtimes with others
or by assistance in preparing foods that they particularly enjoy. The American Academy of Home Care
Physicians (AAHCP) noted in a report published in
May 2004 that the use of orexigenic drugs in the
elderly is ‘‘controversial and not generally FDAapproved.’’

Description
Orexigenic drugs used in the United States as of
2005 are classified as follows:


Mirtazapine. Mirtazapine is a tetracyclic antidepressant that was approved by the Food and Drug
Administration (FDA) in 1996 for the treatment of
major depression. Although researchers do not fully
understand why mirtazapine relieves mood disorders, they think that it increases the levels of noradrenaline and serotonin (chemicals that transmit
nerve impulses across the gaps between cells) in the
brain. Mirtazapine is most often prescribed as an
appetite stimulant for patients who have been previously diagnosed with depression.



Cyproheptadine. Cyproheptadine is an antihistamine given to relieve the symptoms of colds, nasal
allergies, and hay fever. It is also prescribed to relieve
the itching associated with insect bites and stings,
poison ivy, and poison oak. It appears to be most
effective in treating loss of appetite in children and
adults diagnosed with cystic fibrosis.
GALE ENCYCLOPEDIA OF MEDICINE

Anabolic steroids—A group of drugs derived from
the male sex hormone testosterone, most commonly prescribed to promote growth or to help
the body repair tissues weakened by severe illness
or aging. Some anabolic steroids are given as appetite stimulants.



Anorexia—Loss of appetite for food.
Antiemetic—A type of medication given to relieve
or prevent nausea and vomiting. Some appetiteenhancing drugs are also used as antiemetics.
Appetite—The natural instinctive desire for food. It
should be distinguished from hunger, which is the
body’s craving or need for food (either calories or
specific nutrients).
Cachexia—A condition of general ill health, malnutrition, undesired weight loss, and physical
weakness, often associated with cancer.
Off-label—Referring to the use of a drug for a condition or disorder not listed in the official FDA
labeling.
Orexigenic—The medical term for drugs that
increase or stimulate the appetite.
Palliative—Referring to drugs or other therapies
intended to relieve the symptoms of a disease rather
than to cure it.

Recommended dosage
Recommended dosages for orexigenic drugs are
as follows:


Mirtazapine. Mirtazapine is available in 15- and 30mg tablets or disintegrating tablets. The usual starting dose is 15 mg once daily, usually at bedtime. The
drug can be taken with or without food, as the
patient prefers.



Cyproheptadine. Cyproheptadine is taken by mouth,
either as tablets or in liquid form. Adults are usually
given 4 mg three or four times per day. Children
between 2 and 6 years of age are usually given 12
mg per day in 3–4 divided doses while older children
are given 16 mg per day in divided doses.



Dronabinol. As an appetite stimulant, dronabinol is
given as a 2.5-mg capsule twice a day, before lunch
and dinner. Some AIDS patients may be given as
much as 10 mg per day.



Anabolic steroids. Oxandrolone and oxymetholone
are available in the United States and Canada as
tablets, while nandrolone is given by injection. To
build up body tissues after injury or serious illness,
the adult dosage of oxandrolone is a 2.5-mg tablet
taken by mouth two to four times daily for a period
of four weeks, although the total daily dosage may be
raised as high as 20 mg. To treat anemia, oxymetholone is prescribed according to the patient’s body
weight, usually 0.45–2.3 mg per pound of body
weight per day in adults and children. Nandrolone
is given by injection every three to four weeks for a
period of 12 weeks. The usual dosage for women and
girls over 14 is 50–100 mg; for men and boys over 14,

Undernutrition—A type of malnutrition caused by
inadequate food intake or the body’s inability to
make use of needed nutrients.



Dronabinol. Dronabinol is a synthetic version of tetrahydrocannabinol (THC), the mood-altering compound found in marijuana (Cannabis sativa).
Marijuana has been known as an appetite stimulant
for centuries, having been recommended for that purpose by Ayurvedic practitioners and by the Arabic
physician Al Badri, who first described its orexigenic
properties in 1251. Dronabinol is most commonly
used to treat the nausea and vomiting associated with
AIDS and with cancer chemotherapy.



Anabolic steroids. These drugs are given to older persons to increase muscle mass and strength, or to help
patients recovering from severe illness or injury to
regain lost weight.



Megestrol acetate. Megestrol acetate was first
approved by the FDA in 1976 for palliative treatment of metastatic breast or endometrial cancer. It
received additional approval in 1993 for the

GALE ENCYCLOPEDIA OF MEDICINE

Fish oil. Fish oil is recommended by some practitioners as a nutritional supplement for weight loss
caused by cancer or AIDS. It is thought that the
omega-3 fatty acids in fish oil help to reduce the
inflammation associated with some forms of cancer
therapy as well as helping patients regain lost weight.
Although some studies question the effectiveness of
fish oil as a complementary treatment for undesired
weight loss, the National Center for Complementary
and Alternative Medicine (NCCAM) is recruiting
patients as of April 2005 for a clinical trial of fish
oil as a dietary supplement to maintain weight in
patients with pancreatic cancer. The study will be
completed in September 2007.

385

Appetite-enhancing drugs

treatment of anorexia or unexplained weight loss in
patients with AIDS. Researchers do not fully understand how the drug prevents the growth of cancer
cells or how it stimulates appetite.

KEY TERMS

Appetite-enhancing drugs

50–200 mg; for children between the ages of 2 and 13,
15–50 mg.


Megestrol acetate. Megestrol acetate is given as a
liquid suspension in 200-mg doses every 6 hours.



Fish oil. A recommended dose for cancer-induced
weight loss is 12 g daily, taken by mouth. Fish oil is
available in capsules as well as liquid forms.



Anabolic steroids. Patients taking these drugs must
follow a diet high in protein and calories in order to
benefit from the medications, and should be carefully
supervised by their doctor because of possible side
effects. Children or teenagers taking these drugs
should have x-rays every six months to make sure
they are growing normally, as anabolic steroids can
interfere with growth. Patients with diabetes should
check their blood sugar levels with extra care, as
these drugs may cause rapid changes in blood sugar
levels.



Megestrol acetate. This drug should not be used by
pregnant or lactating women, or by women planning
to become pregnant. Women of childbearing age
who are taking megestrol should use a reliable form
of contraception.



Fish oil. Fish oil is not a prescription drug; however,
patients who choose to take cod liver oil as their fish
oil supplement should make sure that they are not
getting more than the safe maximum daily allowances of vitamins A and D. These vitamins tend to build
up in the body and may reach toxic levels. The maximum safe daily level of vitamin A for adults is 3000
micrograms (mcg).

Precautions
Precautions for orexigenic drugs are as follows:






Mirtazapine. In January 2005 the FDA required
labeling changes for mirtazapine to warn of the
increased risk of suicide or self-harm in children or
adolescents taking this drug. Mirtazapine should not
be given to children below 18 years of age, and
should be used with caution in pregnant or lactating
women. Patients taking mirtazapine should not stop
taking it without telling their doctor; it should not be
discontinued abruptly but taken in progressively
smaller doses over a period of time. This precaution
is particularly important in patients who have been
taking the drug for a long time.
Cyproheptadine. This drug should not be given to
patients who suffer acute asthma attacks or are
hypersensitive to antihistamines. It should not be
given to patients who have taken phenelzine
(Nardil), tranylcypromine (Parnate), or other MAO
inhibitors within the last two weeks. Cyproheptadine
should be used cautiously in the elderly and in
patients with glaucoma, high blood pressure, or cardiovascular disease.
Dronabinol. Patients taking dronabinol should
be closely supervised by their doctor, as the
drug may cause unpredictable changes in blood
pressure and heart rate. In addition, it may make
certain mental disorders worse. It also has a high
potential for abuse; for this reason, it should be
used cautiously in patients with a history of
alcohol or drug abuse. Dronabinol should not
be used by nursing mothers because it passes
into breast milk. It should be used with great
caution in children or patients diagnosed with
severe mental illness because of its effects on
the mind. Patients taking dronabinol should
notify their dentist or surgeon before any procedure requiring local or general anesthesia, as the
drug may intensify the effects of the anesthetic.
In addition, these patients should not drive a car
or operate dangerous machinery until they know
whether dronabinol makes them dizzy, drowsy,
or uncoordinated.

386

Side effects
Side effects reported for orexigenic drugs are as
follows:


Mirtazapine. Mirtazapine may cause mood changes,
including worsening depression or thoughts of suicide. It may also cause panic attacks, irritability,
difficulty with impulse control, abnormal levels of
excitement, or difficulty sleeping. Physical side
effects may include sleepiness, dry mouth, constipation, nausea and vomiting, flu-like symptoms, chest
pain, and rapid heartbeat. Patients who have any of
these side effects should consult their doctor at once.



Cyproheptadine. Side effects include drowsiness,
fatigue, dry mouth, skin rash, chest congestion, headache, diarrhea, nausea and vomiting, difficulty urinating, and blurred vision. Patients who experience
urinary or vision problems should consult their doctor at once.



Dronabinol. Dronabinol may cause a variety of
changes in mental status, including delirium, confusion, hallucinations, memory loss, delusions, euphoria
(false sense of well-being), nervousness or anxiety.
Because of the possibility of severe mental side
effects, anyone who has taken an overdose of dronabinol needs immediate emergency medical help. The
drug may also cause clumsiness or lightheadedness,
GALE ENCYCLOPEDIA OF MEDICINE







Anabolic steroids. These drugs have been reported to
cause a rare form of liver disease; patients who notice
yellowing of the eyes or skin, or black, tarry stools,
sore throat and fever, vomiting of blood, or purplish
or reddish spots on the body should contact their
doctor at once. Other side effects include feeling
chilly, diarrhea, muscle cramps, unusual increase or
decrease in sexual desire, acne or oily skin, bone pain,
nausea, or vomiting. Women may notice deepening
of the voice, hair loss, unnatural hair growth (hirsutism), or irregular menstrual periods. Adult males
may notice enlargement of the breasts (gynecomastia), frequent need to urinate, or frequent erections.
Elderly males may have difficulty urinating.
Megestrol acetate. Side effects of megestrol acetate
include swelling of the hands, feet, or lower legs;
headaches; sore breasts; or decreased sexual desire.
Men taking this drug may become impotent. Women
may notice vaginal bleeding or abdominal pain.
Fish oil. Some people taking fish oil as a dietary
supplement experience an increased tendency to
burp followed by a fishy taste in the mouth.

Interactions
Most orexigenic drugs interact with a number of
other medications:


Mirtazapine. Mirtazapine may cause high blood
pressure or abnormally high body temperature if
taken together with MAO inhibitors (furazolidone,
phenelzine, procarbazine, selegiline, or tranylcypromine). It intensifies the sedating (sleep-inducing)
effects of alcohol, benzodiazepine tranquilizers, antihistamines, tricyclic antidepressants, narcotic pain
relievers, and some medications given for high
blood pressure.



Cyproheptadine. Cyproheptadine intensifies and
prolongs the effects of other antihistamines, alcohol,
barbiturates, narcotic pain relievers, benzodiazepine
tranquilizers, and antidepressant medications.



Dronabinol. Dronabinol intensifies the effects of
alcohol and other medications that act as central
nervous system depressants. These groups of drugs
include barbiturates, benzodiazepine tranquilizers,
tetracyclic and tricyclic antidepressants, narcotic
pain relievers, antiseizure medications, antihistamines, muscle relaxants, and anesthetics, including
dental anesthetics.

GALE ENCYCLOPEDIA OF MEDICINE



Anabolic steroids. Anabolic steroids may intensify
the effects of blood thinners (aspirin, coumadin, warfarin). They may increase the risk of liver damage in
patients who are taking phenothiazines, valproic
acid, oral contraceptives containing estrogen, gold
salts, methotrexate, carbamazepine, amiodarone,
mercaptopurine, phenytoin, plicamycin, disulfiram,
daunorubicin,
chloroquine,
methyldopa,
or
naltrexone.



Megestrol acetate. No significant interactions with
other drugs have been reported. Patients taking
megestrol acetate should, however, notify their physician of all other drugs and dietary supplements
(including herbal preparations) that they use on a
regular basis, as dosage adjustments are sometimes
needed.



Fish oil. Fish oil has been reported to intensify the
effects of such blood-thinning medications as coumadin and warfarin. Persons who take these drugs
and wish to use fish oil as a dietary supplement
should consult their doctor first.

Resources
BOOKS

‘‘Malnutrition.’’ Section 1, Chapter 2 in The Merck Manual
of Diagnosis and Therapy, edited by Mark H. Beers,
MD, and Robert Berkow, MD. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
‘‘Protein-Energy Undernutrition.’’ Section 8, Chapter 61 in
The Merck Manual of Geriatrics, edited by Mark H.
Beers, MD, and Robert Berkow, MD. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Wilson, Billie A., Margaret T. Shannon, and Carolyn L.
Stang. Nurses Drug Guide 2000, Stamford, CT:
Appleton & Lange, 2000.
PERIODICALS

Anttila, S. A., and E. V. Leinonen. ‘‘A Review of the
Pharmacological and Clinical Profile of Mirtazapine.’’
CNS Drug Reviews 7 (Fall 2001): 249–264.
Grinspoon, S., and K. Mulligan. ‘‘Weight Loss and Wasting
in Patients Infected with Human Immunodeficiency
Virus.’’ Clinical Infectious Diseases 36 (April 1, 2003)
(Supplement 2): S69–S78.
Holder, H. ‘‘Nursing Management of Nutrition in Cancer
and Palliative Care.’’ British Journal of Nursing 12 (June
12–25, 2003): 667–674.
Homnick, D. N., B. D. Homnick, A. J. Reeves, et al.
‘‘Cyproheptadine Is an Effective Appetite Stimulant in
Cystic Fibrosis.’’ Pediatric Pulmonology 38 (August
2004): 129–134.
Jatoi, A., K. Rowland, C. L. Loprinzi, et al. ‘‘An
Eicosapentaenoic Acid Supplement Versus Megestrol
Acetate Versus Both for Patients with CancerAssociated Wasting: A North Central Cancer
Treatment Group and National Cancer Institute of
387

Appetite-enhancing drugs

dry mouth, fatigue, headache, sweating, facial flushing, diarrhea or constipation, muscle pains, high
blood pressure, seizures, problems in urinating, red
eyes, or vomiting.

Apraxia

Canada Collaborative Project.’’ Journal of Clinical
Oncology 22 (June 15, 2004): 2469–2476.
Jatoi, A., H. E. Windschitl, C. L. Loprinzi, et al.
‘‘Dronabinol Versus Megestrol Acetate Versus
Combination Therapy for Cancer-Associated
Anorexia: A North Central Cancer Treatment Group
Study.’’ Journal of Clinical Oncology 20 (January 15,
2002): 567–573.
Morley, J. E. ‘‘Orexigenic and Anabolic Agents.’’ Clinics in
Geriatric Medicine 18 (November 2002): 853–866.
Vickers, S. P., and G. A. Kennett. ‘‘Cannabinoids and the
Regulation of Ingestive Behaviour.’’ Current Drug
Targets 6 (March 2005): 215–223.
ORGANIZATIONS

American Academy of Home Care Physicians (AAHCP).
P. O. Box 1037, Edgewood, MD 21040-0337. (410) 6767966. Fax: (410) 676-7980. <http://www.aahcp.org>.
American Psychiatric Association (APA). 1000 Wilson
Boulevard, Suite 1825, Arlington, VA 22209-3901.
(800) 368-5777 or (703) 907-7322. Fax: (703) 907-1091.
<http://www.psych.org>.
American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814. (301)
657-3000. <www.ashp.org>.
National Cancer Institute (NCI). NCI Public Inquiries
Office, Suite 3036A, 6116 Executive Boulevard,
MSC8332, Bethesda, MD 20892-8322. (800)
4-CANCER or (800) 332-8615 (TTY).
<www.nci.nih.gov>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <www.fda.gov>.
OTHER

Food and Drug Administration (FDA) MedWatch, January
2005. ‘‘Summary View: Safety Labeling Changes
Approved by FDA Center for Drug Evaluation and
Research (CDER)—January 2005.’’ <http://
www.fda.gov/medwatch/SAFETY/2005/
jan05_quickview.htm>.
Morley, John E., David R. Thomas, and Margaret-Mary G.
Wilson. ‘‘Appetite and Orexigenic Drugs.’’ St. Louis,
MO: Council for Nutrition, Clinical Strategies in LongTerm Care, 2001.
National Center for Complementary and Alternative
Medicine (NCCAM). ‘‘Clinical Trial: A Fish Oil
Supplement to Maintain Body Weight in Pancreatic
Cancer Patients.’’ <http://clinicaltrials.gov/show/
NCT00094562>.
Taler, George, MD, and Christine Ritchie, MD.
‘‘Unintended Weight Loss Guidelines.’’. Edgewood,
MD: American Academy of Home Care Physicians,
2004.

Rebecca J. Frey, PhD

Applied kinesiology see Kinesiology, applied
388

I Apraxia
Definition
Apraxia is neurological condition characterized
by loss of the ability to perform activities that a person
is physically able and willing to do.

Description
Apraxia is caused by brain damage related to
conditions such as head injury, stroke, brain tumor,
and Alzheimer’s disease. The damage affects the
brain’s ability to correctly signal instructions to the
body. Forms of apraxia include the inability to say
some words or make gestures.
Various conditions cause apraxia, and it can affect
people of all ages. A baby might be born with the
condition. A car accident or fall that resulted in head
trauma could lead to apraxia.
From 500,000 to 750,000 people need to be hospitalized each year for head injuries according to the
American Medical Association (AMA). Men between
the ages of 18 and 24 form the largest group of people
with head injuries. While not all severe injuries result
in apraxia, men in that age group are at risk.
Risk factors for strokes include high blood pressure, diabetes, and heart disease. Cigarette smoking
also puts a person at risk for a stroke. Brain tumors
are abnormal tissue growths in the skull. They may be
secondary tumors caused by the spread of cancer
through the body.
There is more than one type of apraxia, and a
person may have one or more form of this condition.
Furthermore, a milder form of apraxia is called
dyspraxia.

Causes and symptoms
Apraxia is caused by conditions that affect parts
of the brain that control movements. Apraxia is a
result of damage to the brain’s cerebral hemispheres.
These are the two halves of the cerebrum and are the
location of brain activities such as voluntary
movements.
Apraxia causes a lapse in carrying out movements
that a person knows how to do, is physically able to
perform, and wants to do. A person may be willing
and able to do something like bathe. However, the
brain does not send the signals that allow the person
to perform the necessary sequence of activities to do
this correctly.
GALE ENCYCLOPEDIA OF MEDICINE

CT scanning—Computer tomography scanning is a
diagnostic imaging tool that uses x rays sent
through the body at different angles.
MRI—Magnetic resonance imaging is a diagnostic
imaging tool that utilizes an electromagnetic field
and radio waves.

Types of apraxia
There are several types of apraxia, and a patient
could be diagnosed with one or more forms of this
condition. The types of apraxia include:


Buccofacial or orofacial apraxia is the inability of a
person to follow through on commands involving
face and lip motions. These activities include coughing, licking the lips, whistling, and winking. Also
known as facial-oral apraxia, it is the most common
form of apraxia, according to the National Institute
of Neurological Disorders and Stroke (NINDS).



Limb-kinetic apraxia is the inability to make precise
movements with an arm or leg.



Ideomotor apraxia is the inability to make the proper
movement in response to a command to pantomime
an activity like waving.



Constructional apraxia is the inability to copy, draw,
or build simple figures.



Ideational apraxia is the inability to do an activity
that involves performing a series of movements in a
sequence. A person with this condition could have
trouble dressing, eating, or bathing. It is also known
as conceptual apraxia.



Oculomotor apraxia is characterized by difficulty
moving the eyes.



Verbal apraxia is a condition involving difficulty
coordinating mouth and speech movements. It is
referred to as apraxia of speech by organizations
including the American Speech Language Hearing
Association (ASHA).

A baby who does not coo or babble may display a
symptom of apraxia of speech, according to ASHA. A
young child may only say a few consonant sounds, and
an older child may have difficulty imitating speech. An
adult also has this difficulty. Other symptoms include
saying the wrong words. A person wants to say
‘‘kitchen,’’ but says ‘‘bipem’’ instead, according to an
ASHA report.
GALE ENCYCLOPEDIA OF MEDICINE

A person diagnosed with apraxia may also have
aphasia, a condition caused by damage to the brain’s
speech centers. This results in difficulty reading, witting, speaking, and understanding when others speak.
Post-apraxia changes
A person with apraxia could experience frustration about difficulty communicating or trouble performing tasks. In some cases, the condition could
affect the person’s ability to live independently.

Diagnosis
Diagnosis of apraxia could begin with testing of
its underlying cause. Testing for conditions like a
stroke or cancer includes the MRI (magnetic resonance
imaging) and CT scanning (computer tomography
scanning). A brain biopsy is used to measure changes
caused by Alzheimer’s disease. In all cases, the physician takes a family history. Head trauma that could
cause apraxia is first treated in the emergency room.
Other diagnostic treatment is related to identifying the type of apraxia. For example, the physician
may ask the patient to demonstrate how to blow out a
candle, wave, use a fork, or use a toothbrush.
Assessment for speech apraxia in children
includes a hearing evaluation to determine if difficulty
in speaking is related to a hearing loss. If the condition
appears related to apraxia, a speech-language pathologist examines muscle development in the jaw, lips,
and tongue. The examination of adults and children
includes an evaluation of how words are pronounced
individually and in conversation. The pathologist
observes how the patient breathes when speaking
and the ability to perform actions like smiling.
The costs of diagnosis vary because the process
could include examinations and diagnostic screening
related to the underlying cost of the apraxia. Insurance
generally covers part of these costs.

Treatment
The treatment for apraxia usually involves rehabilitation through speech-language therapy, physical
therapy, or occupational therapy. In addition, treatment such as chemotherapy is administered for the
condition that caused the apraxia.
Family education is an important component of
apraxia treatment. The rehabilitation process takes
time, and relatives can offer encouragement and support
to the patient. They may be asked to help the patient
with in-home exercises. Furthermore, family members
sometimes need to take on the role of caregivers.
389

Apraxia

KEY TERMS

Apraxia

Speech-language therapy
Speech-language therapy focuses on helping the
patients learn or regain communication skills.
Therapists teach exercises to strengthen facial muscles
used in speech. Other exercises concentrate on patients
learning to correctly pronounce sounds and then turn
those sounds into words.
In cases where apraxia limits the ability to speak,
therapists help patients develop alternate means of
communication. These alternatives range from gesturing to using a portable computer that writes and produces speech, according to ASHA.
Occupational and physical therapies
Occupational and physical therapies focus on
helping patients regain the skills impaired by apraxia.
Physical therapy exercises concentrate on areas such
as mobility and balance. Occupational therapy helps
patients relearn daily living skills.

be required, and some people with dementia require
supervised, longterm care.

Prevention
The methods of preventing apraxia focus on preventing the underlying causes of this condition. This
may not be entirely possible when there is a family
history of conditions such as stroke, dementia, and
cancer. However, a person at risk by not smoking,
exercising, and eating a diet based on the American
Heart Association guidelines.
Head injury can be prevented by wearing a helmet
when participating in activities like sports and bicycling. Wearing a seatbelt when in a vehicle also helps
reduce the risk of head injury.
Resources
BOOKS
PERIODICALS
ORGANIZATIONS

Treatment costs
The costs of therapy vary by the type of treatment,
regional location, and where the therapy is offered.
Fees can range for $40 per hour for in-office speech
therapy for a child to $85 per hour for in-home physical or occupational therapy for a senior citizen. Part of
therapy costs may be covered by insurance.

Alternative treatment
Most alternative treatments target Alzheimer’s
disease and other conditions that cause apraxia.
Herbal remedies thought to help people with
Alzheimer’s include ginkgo biloba, a plant extract.
However, organizations including the Alzheimer’s
Association caution that the effectiveness and safety
of this herbal remedy has not been evaluated by the
U.S. Food and Drug Administration. The government
does not require a review of supplements like ginkgo.
Furthermore, there is a risk of internal bleeding if
ginkgo is taken in combination with aspirin and
blood-thinning medications.

Prognosis
The prognosis for apraxia depends on factors such
as what caused the condition. While Alzheimer’s is a
degenerative condition, a child with verbal apraxia or
a stroke patient could make progress.
In some cases, treatment helps a person to relearn
or acquire skills needed to function. A caregiver may
390

American Speech Language Hearing Association. 10801
Rockville Pike, Rockville, MD 20852-3279. 800-6388255. <http://www.asha.org>.
Alzheimer’s Association. 225 North Michigan Avenue,
Floor 17, Chicago, IL 60601. 800-272-3900. <http://
www.alz.org>.
National Institute of Neurological Disorders and Stroke,
NIH Neurological Institute. P.O. Box 5801, Bethesda,
MD 20824. 800-352-9424.<http://
www.ninds.nih.gov>.
National Rehabilitation Information Center. 4200 Forbes
Boulevard Suite 202, Lanham, MD 20706-4829. 800346-2742. <http://www.naric.com>.
National Stroke Association. 9707 East Easter Lane,
Englewood, CO 80112. 1-800-787-6537. <http://
www.stroke.org>.
OTHER

‘‘Apraxia in Adults.’’ American Speech Language Hearing
Association. 2005. [cited March 29, 2005]. <http://
www.asha.org/public/speech/disorders/
apraxia_adults.htm>.
‘‘Childhood Apraxia of Speech.’’ American Speech
Language Hearing Association. 2005. [cited March 29,
2005]. <http://www.asha.org/public/speech/disorders/
Developmental-Apraxia-of-Speech.htm>.
Jacobs, Daniel H., M.D.‘‘Apraxia and Related Syndromes.’’
e-medicine. October 27, 2004 [cited March 29, 2005].
<http://www.emedicine.com/neuro/topic438.htm>.
‘‘NINDS Apraxia Information Page.’’ National Institute of
Neurological Disorders and Stroke February 09, 2005
[cited March 29, 2005]. <http://www.ninds.nih.gov/
disorders/apraxia/apraxia.htm>.

Liz Swain,
GALE ENCYCLOPEDIA OF MEDICINE

APTT see Partial thromboplastin time
Arachnodactyly see Marfan syndrome

I Arbovirus encephalitis
Definition
Encephalitis is a serious inflammation of the
brain, Arbovirus encephalitis is caused by a virus
from the Arbovirus group. The term arbovirus stands
for Arthro-pod-borne virus because these viruses are
passed to humans by members of the phylum
Arthropoda (which includes insects and spiders).

Description
Of the huge number of arboviruses known to
exist, about 80 types are responsible for human disease. In addition to the virus, there are usually two
other types of living creatures involved in the cycle
leading to human disease. When large quantities of
virus are present in an arthropod (often a tick or
mosquito), the viruses are passed to a bird or small
mammal when the arthropod attempts to feed on the
blood of that creature. The virus thrives within the
new host, sometimes causing illness, sometimes not.
More ticks or mosquitoes are infected with the virus
when they feed on the host’s blood. Eventually, a tick
or mosquito bites a human, and the virus is passed
along. Just a few types of arboviruses cycle only
between arthropods and humans, with no intermediate stop in a bird or small mammal.
Because the arboviruses require an arthropod to
pass them along to humans, the most common times
of year for these illnesses include summer and fall,
when mosquitoes and ticks are most prevalent.
Damp environments favor large populations of mosquitoes, and thus also increase the risk of arbovirus
infections.
The major causes of arbovirus encephalitis
include the members of the viral families alphavirus
(causing Eastern equine encephalitis, Western equine
encephalitis, and Venezuelan equine encephalitis), flavivirus (responsible for St. Louis encephalitis,
Japanese encephalitis, Tick-borne encephalitis,
Murray Valley encephalitis, Russian spring-summer
encephalitis, and Powassan), and bunyavirus (causing
California encephalitis).
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Arthropods—A phylum name referring to certain
insects (including mosquitoes and ticks) and spiders.
Encephalitis—A condition in which the brain swells.

In the United States, the most important types of
arbovirus encephalitis include Western equine encephalitis (WEE), Eastern equine encephalitis (EEE),
St. Louis encephalitis, and California encephalitis.
WEE strikes young infants in particular, with a 5%
chance of death from the illness. Of those who survive,
about 60% suffer permanent brain damage. EEE
strikes infants and children, with a 20% chance of
death, and a high rate of permanent brain damage
among survivors. St. Louis encephalitis tends to strike
adults older than 40 years of age, and older patients
tend to have higher rates of death and long-term disability from the infection. California virus primarily
strikes 5-18 year olds, with a lower degree of permanent brain damage.

Causes and symptoms
Encephalitis occurs because specific arboviruses
have biochemical characteristics which cause them to
be particularly attracted to the cells of the brain and the
nerves. The virus causes cell death and inflammation,
with fever and swelling within the brain and nerves. The
membranous coverings of the brain and spinal cord
(the meninges) may also become inflamed, a condition
called meningitis. The brain is swollen, and patches of
bleeding occur throughout the brain and spinal cord.
Patients with encephalitis suffer from headaches,
fever, nausea and vomiting, stiff neck, and sleepiness.
As the disease progresses, more severe symptoms
develop, including tremors, confusion, seizures,
coma, and paralysis. Loss of function occurs when
specific nerve areas are damaged and/or killed.

Diagnosis
Early in the disease, laboratory testing of blood
may reveal the presence of the arbovirus. The usual
technique used to verify the presence of arbovirus
involves injecting the patient’s blood into the brain
of a newborn mouse, then waiting to see if the mouse
develops encephalitis. Diagnosis is usually based on
the patient’s symptoms, history of tick or mosquito
bites, and knowledge that the patient has been in an
area known to harbor the arbovirus.
391

Arbovirus encephalitis

APSGN see Acute poststreptococcal
glomerulonephritis

Aromatherapy

Treatment
Treatment is mostly supportive, meaning it is
directed at improving the symptoms, but does not
shorten the course of the illness. The main concerns
of treatment involve lowering fever, treating pain,
avoiding dehydration or other chemical imbalances,
and decreasing swelling in the brain with steroids.

Aromatherapy Oils

Name

Description

Conditions treated

Bay laurel

Antiseptic, diuretic,
sedative, etc.

Clary sage

Relaxant, anticonvulsive,
antiinflammatory, and
antiseptic

Eucalyptus

Antiseptic, antibacterial,
astringent, expectorant,
and analgesic

Chamomile

Sedative,
antiinflammatory,
antiseptic, and pain
reliever

Lavender

Analgesic, antiseptic,
calming/soothing

Peppermint

Pain reliever

Rosemary

Antiseptic, stimulant,
and diuretic

There are immunizations available against EEE
and WEE. These have primarily been used to safeguard laboratory workers who have regular exposure
to these viruses.

Tarragon

Diuretic, laxative,
antispasmodic, and
stimulant

Tea tree

Antiseptic and soothing

Resources

Thyme

Stimulant, antiseptic,
antibacterial, and
antispasmodic

Digestive problems,
bronchitis, common cold,
influenza, and scabies
and lice. CAUTION: Don’t
use if pregnant.
Menstrual and menopausal
symptoms, burns, eczema,
and anxiety. CAUTION:
Don’t use if pregnant.
Boils, breakouts, cough,
common cold, influenza,
and sinusitis. CAUTION:
Not to be taken orally.
Hay fever, burns, acne,
arthritis, digestive
problems, sunburn, and
menstrual an menopausal
symptoms.
Headache, depression,
insomnia, stress, sprains,
and nausea.
Indigestion, nausea,
headache, motion
sickness, and muscle
pain.
Indigestion, gas, bronchitis,
fluid retention, and
influenza. CAUTION: Don’t
use if pregnant or have
epilepsy or hypertension.
Menstrual and menopausal
symptoms, gas, and
indigestion. CAUTION:
Don’t use if pregnant.
Common cold, bronchitis,
abscesses, acne, vaginitis,
and burns.
Cough, laryngitis,
diarrhea, gas, and
intestinal worms.
CAUTION: Don’t use if
pregnant or have
hypertension.

Prognosis
Prognosis depends on the particular type of arbovirus causing disease, and on the age and prior health
status of the patient. Death rates range all the way up
to 20% for arbovirus encephalitis, and the rates of
lifelong effects due to brain damage reach 60% for
some types of arboviruses.

Prevention
Prevention involves avoiding contact with
arthropods which carry these viruses. This means
wearing appropriate insect repellents, and dressing
properly in areas known to be infested. Insecticides
and the avoidance of collections of standing water
(which are good breeding ground for arthropods) is
also effective at decreasing arthropod populations.

BOOKS

Stoffman, Phyllis. The Family Guide to Preventing and
Treating 100 Infectious Diseases. New York: John
Wiley & Sons, 1995.

Rosalyn Carson-DeWitt, MD

ARDS see Adult respiratory distress
syndrome

I Aromatherapy
Definition
Aromatherapy is the therapeutic use of plantderived, aromatic essential oils to promote physical
and psychological well-being. It is sometimes used in
combination with massage and other therapeutic techniques as part of a holistic treatment approach.
392

Purpose
Aromatherapy offers diverse physical and psychological benefits, depending on the essential oil or
oil combination and method of application used.
Some common medicinal properties of essential oils
used in aromatherapy include: analgesic, antimicrobial, antiseptic, anti-inflammatory, astringent, sedative, antispasmodic, expectorant, diuretic, and
sedative. Essential oils are used to treat a wide range
of symptoms and conditions, including, but not limited to, gastrointestinal discomfort, skin conditions,
menstrual pain and irregularities, stress-related conditions, mood disorders, circulatory problems, respiratory infections, and wounds.
GALE ENCYCLOPEDIA OF MEDICINE

Aromatherapy

Limbic system of the brain

Olfactory bulb

Nasal cavity

Aromatic substances

Olfactory
neurons

As a holistic therapy, aromatherapy is believed to benefit both the mind and body. Here, the aromatic substances from a flower
stimulates the olfactory bulb and neurons. The desired emotional response (such as relaxation) is activated from the limbic
system of the brain. (Illustration by Electronic Illustrators Group.)

Description
Origins
Aromatic plants have been employed for their
healing, preservative, and pleasurable qualities
throughout recorded history in both the East and
West. As early as 1500 B.C. the ancient Egyptians
used waters, oils, incense, resins, and ointments
scented with botanicals for their religious ceremonies.
There is evidence that the Chinese may have
recognized the benefits of herbal and aromatic remedies much earlier than this. The oldest known herbal
text, Shen Nung’s Pen Ts’ao (c. 2700-3000 B.C.) catalogs over 200 botanicals. Ayurveda, a practice of traditional Indian medicine that dates back over 2,500
years, also used aromatic herbs for treatment.
The Romans were well-known for their use of
fragrances. They bathed with botanicals and integrated
them into their state and religious rituals. So did the
Greeks, with a growing awareness of the medicinal
properties of herbs, as well. Greek physician and surgeon Pedanios Dioscorides, whose renown herbal text
GALE ENCYCLOPEDIA OF MEDICINE

De Materia Medica (60 A.D.) was the standard textbook
for Western medicine for 1,500 years, wrote extensively
on the medicinal value of botanical aromatics. The
Medica contained detailed information on over 500
plants and 4,740 separate medicinal uses for them,
including an entire section on aromatics.
Written records of herbal distillation are found as
early as the first century A.D., and around 1000 A.D.,
the noted Arab physician and naturalist Avicenna
described the distillation of rose oil from rose petals,
and the medicinal properties of essential oils in his
writings. However, it wasn’t until 1937, when French
chemist
René-Maurice
Gattefossé
published
Aromatherapie: Les Huiles essentielles, hormones ve´ge´
tales, that aromatherapie, or aromatherapy, was
introduced in Europe as a medical discipline.
Gattefossé, who was employed by a French perfumeur, discovered the healing properties of lavender
oil quite by accident when he suffered a severe burn
while working and used the closest available liquid,
lavender oil, to soak it in.
In the late 20th century, French physician Jean
Valnet used botanical aromatics as a front line
393

Aromatherapy

KEY TERMS
Antiseptic—Inhibits the growth of microorganisms.
Bactericidal—An agent that destroys bacteria (e.g.,
Staphylococci aureus, Streptococci pneumoniae,
Escherichia coli, Salmonella enteritidis).

and spiritual needs of a patient as well as their physical treatment.
Phototoxic—Causes a harmful skin reaction when
exposed to sunlight.

Carrier oil—An oil used to dilute essential oils for
use in massage and other skin care applications.
Contact dermatitis—Skin irritation as a result of contact with a foreign substance.

Remedy antidote—Certain foods, beverages, prescription medications, aromatic compounds, and
other environmental elements that counteract the
efficacy of homeopathic remedies.

Essential oil—A volatile oil extracted from the
leaves, fruit, flowers, roots, or other components of
a plant and used in aromatherapy, perfumes, and
foods and beverages.

Steam distillation—A process of extracting essential
oils from plant products through a heating and evaporation process.
Volatile—Something that vaporizes or evaporates
quickly when exposed to air.

Holistic—A practice of medicine that focuses on the
whole patient, and addresses the social, emotional,

treatment for wounded soldiers in World War II. He
wrote about his use of essential oils and their healing
and antiseptic properties, in his 1964 book
Aromatherapie, traitement des maladies par les essences
des plantes, which popularized the use of essential oils
for medical and psychiatric treatment throughout
France. Later, French biochemist Mauguerite Maury
popularized the cosmetic benefits of essential oils, and
in 1977 Robert Tisserand wrote the first English language book on the subject, The Art of Aromatherapy,
which introduced massage as an adjunct treatment to
aromatherapy and sparked its popularity in the
United Kingdom.
In aromatherapy, essential oils are carefully
selected for their medicinal properties. As essential oils
are absorbed into the bloodstream through application
to the skin or inhalation, their active components trigger certain pharmalogical effects (e.g., pain relief ).
In addition to physical benefits, aromatherapy
has strong psychological benefits. The volatility of an
oil, or the speed at which it evaporates in open air, is
thought to be linked to the specific psychological effect
of an oil. As a rule of thumb, oils that evaporate
quickly are considered emotionally uplifting, while
slowly-evaporating oils are thought to have a calming
effect.
Essential oils commonly used in aromatherapy
treatment include:


Roman chamomile (Chamaemelum nobilis). An antiinflammatory and analgesic. Useful in treating otitis
media (earache), skin conditions, menstrual pains,
and depression.

394



Clary sage (Salvia sclarea). This natural astringent is
not only used to treat oily hair and skin, but is also
said to be useful in regulating the menstrual cycle,
improving mood, and controlling high blood pressure. Clary sage should not be used by pregnant
women.



Lavender (Lavandula officinalis). A popular aromatherapy oil which mixes well with most essential
oils, lavender has a wide range of medicinal and
cosmetic applications, including treatment of insect
bites, burns, respiratory infections, intestinal discomfort, nausea, migraine, insomnia, depression, and
stress.



Myrtle (Myrtus communis). Myrtle is a fungicide,
disinfectant, and antibacterial. It is often used in
steam aromatherapy treatments to alleviate the
symptoms of whooping cough, bronchitis, and other
respiratory infections.



Neroli (bitter orange), (Citrus aurantium). Citrus oil
extracted from bitter orange flower and peel and
used to treat sore throat, insomnia, and stress and
anxiety-related conditions.



Sweet orange (Citrus sinensis). An essential oil used
to treat stomach complaints and known for its
reported ability to lift the mood while relieving stress.



Peppermint (Mentha piperita). Relaxes and soothes
the stomach muscles and gastrointestinal tract.
Peppermint’s actions as an anti-inflammatory, antiseptic, and antimicrobial also make it an effective
skin treatment, and useful in fighting cold and flu
symptoms.
GALE ENCYCLOPEDIA OF MEDICINE

Rosemary (Rosmarinus officinalis). Stimulating
essential oil used to treat muscular and rheumatic
complaints, as well as low blood pressure, gastrointestinal problems, and headaches.



Tea tree (Melaleuca alternifolia). Has bactericidal,
virucidal, fungicidal, and anti-inflammatory properties that make it a good choice for fighting infection.
Recommended for treating sore throat and respiratory infections, vaginal and bladder infections,
wounds, and a variety of skin conditions.



Ylang ylang (Cananga odorata). A sedative essential
oil sometimes used to treat hypertension and
tachycardia.

Essential oils contain active agents that can have
potent physical effects. While some basic aromatherapy home treatments can be self-administered, medical aromatherapy should always be performed under
the guidance of an aromatherapist, herbalist, massage
therapist, nurse, or physician.

almond, grapeseed, hazelnut, apricot seed, or peach
kernel, may be absorbed more easily by the skin.
Standard dilutions of essential oils in carrier oils
range from 2–10%. However, some oils can be used
at higher concentrations, and others should be diluted
further for safe and effective use. The type of carrier
oil used and the therapeutic use of the application
may also influence how the essential oil is mixed.
Individuals should seek guidance from a healthcare
professional and/or aromatherapist when diluting
essential oils.
Massage is a common therapeutic technique
used in conjunction with aromatherapy to both
relax the body and thoroughly administer the essential oil treatment. Essential oils can also be used in
hot or cold compresses and soaks to treat muscle
aches and pains (e.g., lavender and ginger). As a
sore throat remedy, antiseptic and soothing essential
oils (e.g., tea tree and sage) can be thoroughly
mixed with water and used as a gargle or
mouthwash.

Inhalation
The most basic method of administering aromatherapy is direct or indirect inhalation of essential
oils. Several drops of an essential oil can be applied
to a tissue or handkerchief and gently inhaled. A
small amount of essential oil can also be added to a
bowl of hot water and used as a steam treatment.
This technique is recommended when aromatherapy
is used to treat respiratory and/or skin conditions.
Aromatherapy steam devices are also available commercially. A warm bath containing essential oils can
have the same effect as steam aromatherapy, with
the added benefit of promoting relaxation. When
used in a bath, water should be lukewarm rather
than hot to slow the evaporation of the oil.
Essential oil diffusers, vaporizers, and light bulb
rings can be used to disperse essential oils over a large
area. These devices can be particularly effective in
aromatherapy that uses essential oils to promote a
healthier home environment. For example, eucalyptus
and tea tree oil are known for their antiseptic qualities
and are frequently used to disinfect sickrooms, and
citronella and geranium can be useful in repelling
insects.
Direct application
Because of their potency, essential oils are diluted
in a carrier oil or lotion before being applied to the
skin to prevent an allergic skin reaction. The carrier oil
can be a vegetable or olive based one, such as wheat
germ or avocado. Light oils, such as safflower, sweet
GALE ENCYCLOPEDIA OF MEDICINE

Internal use
Some essential oils can be administered internally
in tincture, infusion, or suppository form to treat certain symptoms or conditions; however, this treatment
should never be self-administered. Essential oils
should only be taken internally under the supervision
of a qualified healthcare professional.
As non-prescription botanical preparations, the
essential oils used in aromatherapy are typically not
paid for by health insurance. The self-administered
nature of the therapy controls costs to some degree.
Aromatherapy treatment sessions from a professional aromatherapist are not covered by health
insurance in most cases, although aromatherapy performed in conjunction with physical therapy, nursing, therapeutic massage, or other covered medical
services may be. Individuals should check with their
insurance provider to find out about their specific
coverage.
The adage ‘‘You get what you pay for’’ usually
applies when purchasing essential oils, as bargain oils
are often adulterated, diluted, or synthetic. Pure essential oils can be expensive; and the cost of an oil will
vary depending on its quality and availability.

Preparations
The method of extracting an essential oil varies by
plant type. Common methods include water or steam
distillation and cold pressing. Quality essential oils
395

Aromatherapy



Aromatherapy

should be unadulterated and extracted from pure
botanicals. Many aromatherapy oils on the market
are synthetic and/or diluted, contain solvents, or are
extracted from botanicals grown with pesticides or
herbicides. To ensure best results, essential oils should
be made from pure organic botanicals and labeled by
their full botanical name. Oils should always be stored
dark bottles out of direct light.
Before using essential oils on the skin, individuals should perform a skin patch test by applying
a small amount of the diluted oil behind the wrist
and covering it with a bandage or cloth for up to
12 hours. If redness or irritation occurs, the oil
should be diluted further and a second skin test
performed, or it should be avoided altogether.
Individuals should never apply undiluted essential
oils to the skin unless advised to do so by a trained
healthcare professional.

Precautions
Individuals should only take essential oils
internally under the guidance and close supervision
of a health-care professional. Some oils, such as
eucalyptus, wormwood, and sage, should never be
taken internally. Many essential oils are highly
toxic and should never be used at all in aromatherapy. These include (but are not limited to) bitter
almond, pennyroyal, mustard, sassafras, rue, and
mugwort.
Citrus-based essential oils, including bitter and
sweet orange, lime, lemon, grapefruit, and tangerine,
are phototoxic, and exposure to direct sunlight should
be avoided for at least four hours after their
application.
Other essential oils, such as cinnamon leaf,
black pepper, juniper, lemon, white camphor,
eucalyptus blue gum, ginger, peppermint, pine
needle, and thyme can be extremely irritating to
the skin if applied in high enough concentration
or without a carrier oil or lotion. Caution should
always be exercised when applying essential oils
topically. Individuals should never apply undiluted essential oils to the skin unless directed to
do so by a trained healthcare professional and/or
aromatherapist.
Individuals taking homeopathic remedies should
avoid black pepper, camphor, eucalyptus, and peppermint essential oils. These oils may act as a remedy
antidote to the homeopathic treatment.
Children should only receive aromatherapy treatment under the guidance of a trained aromatherapist
396

or healthcare professional. Some essential oils may not
be appropriate for treating children, or may require
additional dilution before use on children.
Certain essential oils should not be used by pregnant or nursing women or by people with specific illnesses or physical conditions. Individuals suffering
from any chronic or acute health condition should
inform their healthcare provider before starting treatment with any essential oil.
Asthmatic individuals should not use steam inhalation for aromatherapy, as it can aggravate their
condition.
Essential oils are flammable, and should be kept
away from heat sources.

Side effects
Side effects vary by the type of essential oil used.
Citrus-based essential oils can cause heightened sensitivity to sunlight. Essential oils may also cause contact
dermatitis, an allergic reaction characterized by redness and irritation. Anyone experiencing an allergic
reaction to an essential oil should discontinue its use
and contact their healthcare professional for further
guidance. Individuals should do a small skin patch test
with new essential oils before using them extensively
(see ‘‘Preparations’’ above).

Research and general acceptance
The antiseptic and bactericidal qualities of some
essential oils (such as tea tree and peppermint) and
their value in fighting infection has been detailed
extensively in both ancient and modern medical
literature.
Recent research in mainstream medical literature
has also shown that aromatherapy has a positive
psychological impact on patients, as well. Several
clinical studies involving both post-operative and
chronically ill subjects showed that massage with
essential oils can be helpful in improving emotional
well-being, and consequently, promoting the healing
process.
Today, the use of holistic aromatherapy is widely
accepted in Europe, particularly in Great Britain,
where it is commonly used in conjunction with massage as both a psychological and physiological healing
tool. In the United States, where aromatherapy is
often misunderstood as solely a cosmetic treatment,
the mainstream medical community has been slower
to accept it.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

BOOKS

Schnaubelt, Kurt. Medical Aromatherapy: Healing With
Essential Oils. Berkeley, CA: Frog Ltd, 1999.
ORGANIZATIONS

National Association of Holistic Aromatherapy. 836 Hanley
Industrial Court, St. Louis, MO 63144. (888) ASKNAHA. <http://www.naha.org>.

Paula Anne Ford-Martin

Bradycardia—A slow heart rate. Bradycardia is one
of the two types of arrhythmia
Electrocardiogram—A test which uses electric sensors placed on the body to monitor the heartbeat.
Electrophysiology study—A test using cardiac
catheterization to stimulate an electrical current
to provoke an arrhythmia. The test identifies the
origin of arrhythmias and is used to test the effectiveness of antiarrhythmic drugs.
Tachycardia—A fast heart rate. Tachycardia is one
of the two types of arrhythmia.

I Arrhythmias
Definition
An arrhythmia is an abnormality in the heart’s
rhythm, or heartbeat pattern. The heartbeat can be
too slow, too fast, have extra beats, skip a beat, or
otherwise beat irregularly.

Description

Slow heart rates (less than 60 beats per minute) are
called bradycardias, while fast heart rates (more than
100 beats per minute) are called tachycardias.
Bradycardia can result in poor circulation of blood,
and, hence, a lack of oxygen throughout the body,
especially the brain. Tachycardias also can compromise the heart’s ability to pump effectively because the
ventricles do not have enough time to completely fill.

Arrhythmias are deviations from the normal
cadence of the heartbeat, which cause the heart to
pump improperly. The normal heartbeat starts in the
right atrium, where the heart’s natural pacemaker (the
sinus node) sends an electrical signal to the center of
the heart to the atrioventricular node. The atrioventricular node then sends signals into the main pumping
chamber to make the ventricle contract. Arrhythmias
occur when the heartbeat starts in a part of the heart
other than the sinus node, an abnormal rate or rhythm
develops in the sinus node, or a heart conduction
‘‘block’’ prevents the electrical signal from traveling
down the normal pathway.

Arrhythmias are characterized by their site of
origin: the atria or the ventricles. Supraventricular
arrhythmias occur in the upper areas of the heart and
are less serious than ventricular arrhythmias.
Ventricular fibrillation is the most serious arrhythmia
and is fatal unless medical help is immediate.

More than four million Americans have arrhythmias, most of which are harmless. Middle-aged
adults commonly experience arrhythmias. As people
age, the probability of experiencing an arrhythmia
increases. Arrhythmias often occur in people who
do not have heart disease. In people with heart disease, it is usually the heart disease which is dangerous, not the arrhythmia. Arrhythmias often occur
during and after heart attacks. Some types of
arrhythmias, such as ventricular tachycardia, are
serious and even life threatening. In the United
States, arrhythmias are the primary cause of sudden
cardiac death, accounting for more than 350,000
deaths each year.

Symptoms of an arrhythmia include a fast heartbeat, pounding or fluttering chest sensations, skipping
a heartbeat, ‘‘flip-flops,’’ dizziness, faintness, shortness
of breath, and chest pains.

GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
In many cases, the cause of an arrhythmia is
unknown. Known causes of arrhythmias include
heart disease, stress, caffeine, tobacco, alcohol, diet
pills, and decongestants in cough and cold medicines.

Diagnosis
Examination with a stethoscope, electrocardiograms, and electrophysiologic studies is used to diagnose arrhythmias. Sometimes arrhythmias can be
identified by listening to the patient’s heart through
a stethoscope, but, since arrhythmias are not always
present, they may not occur during the physical
exam.
397

Arrhythmias

Resources

Arrhythmias

An electrocardiogram (ECG) shows the heart’s
activity and may reveal a lack of oxygen from poor
circulation (ischemia). Electrodes covered with conducting jelly are placed on the patient’s chest, arms,
and legs. They send impulses of the heart’s activity
through an electrical activity monitor (oscilloscope)
to a recorder that traces them on paper. The test
takes about 10 minutes and is performed in a physician’s office. Another type of ECG, commonly known
as the exercise stress test, measures how the heart and
blood vessels respond to exertion while the patient is
exercising on a treadmill or a stationary bike. This test
is performed in a physician’s office or an exercise
laboratory and takes 15-30 minutes. Other types of
ECGs include 24-hour ECG monitoring and transtelephonic monitoring. In 24-hour ECG (Holter)
monitoring, the patient wears a small, portable tape
recorder connected to disks on his/her chest that
record the heart’s rhythm during daily activities.
Transtelephonic monitoring can identify arrhythmias
that occur infrequently. Similar to Holter monitoring,
transtelephonic monitoring can continue for days or
weeks, and it enables patients to send the ECG via
telephone to a monitoring station when an arrhythmia
is felt, or the patient can store the information in the
recorder and transmit it later.
Electrophysiologic studies are invasive procedures performed in a hospital to identify the origin of
serious arrhythmias and responses to various treatments. They involve cardiac catheterization, in which
catheters tipped with electrodes are passed from a vein
in the arm or leg through the blood vessels into the
heart. The electrodes record impulses in the heart,
highlighting where the arrhythmia starts. During the
procedure, physicians can test the effects of various
drugs by provoking an arrhythmia through the electrodes and trying different drugs. The procedure takes
one to three hours, during which the patient is awake
but mildly sedated. Local anesthetic is injected at the
catheter insertion sites.

Treatment
Many arrhythmias do not require any treatment.
For serious arrhythmias, treating the underlying heart
disease sometimes controls the arrhythmia. In some
cases, the arrhythmia itself is treated with drugs, electrical shock (cardioversion), automatic implantable
defibrillators, artificial pacemakers, catheter ablation,
or surgery. Supraventricular arrhythmias often can be
treated with drug therapy. Ventricular arrhythmias
are more complex to treat.
Drug therapy can manage many arrhythmias, but
finding the right drug and dose requires care and can
398

take some time. Common drugs for suppressing
arrhythmias include beta-blockers, calcium channel
blockers, quinidine, digitalis preparations, and procainamide. Because of their potential serious side effects,
stronger, desensitizing drugs are used only to treat lifethreatening arrhythmias. All of the drugs used to treat
arrhythmias have possible side effects, ranging from
mild complications with beta-blockers and calcium
channel blockers to more serious effects of desensitizing drugs that can, paradoxically, cause arrhythmias
or make them worse. Response to drugs is usually
measured by ECG, Holter monitor, or electrophysiologic study.
In emergency situations, cardioversion or defibrillation (the application of an electrical shock to the
chest wall) is used. Cardioversion restores the heart
to its normal rhythm. It is followed by drug therapy to
prevent recurrence of the arrhythmia.
Artificial pacemakers that send electrical signals
to make the heart beat properly can be implanted
under the skin during a simple operation. Leads from
the pacemaker are anchored to the right side of the
heart. Pacemakers are used to correct bradycardia and
are sometimes used after surgical or catheter ablation.
Automatic implantable defibrillators correct lifethreatening ventricular arrhythmias by recognizing
them and then restoring a normal heart rhythm by
pacing the heart or giving it an electric shock. They
are implanted within the chest wall without major
surgery and store information for future evaluation
by physicians. Automatic implantable defibrillators
have proven to be more effective in saving lives than
drugs alone. They often are used in conjunction with
drug therapy.
Ablation, a procedure to alter or remove the
heart tissue causing the arrhythmia in order to prevent a recurrence, can be performed through a catheter or surgery. Supraventricular tachycardia can be
treated successfully with ablation. Catheter ablation
is performed in a catheterization laboratory with the
patient under sedation. A catheter equipped with a
device that maps the heart’s electrical pathways is
inserted into a vein and is threaded into the heart.
High-frequency radio waves are then used to remove
the pathway(s) causing the arrhythmia. Surgical
ablation is similar in principle but it is performed in
a hospital, using a cold probe instead of radio waves
to destroy tissue. Ablation treatments are used when
medications fail.
Maze surgery treats atrial fibrillation by making
multiple incisions through the atrium to allow electrical impulses to move effectively. This is often
GALE ENCYCLOPEDIA OF MEDICINE

Art therapy

recommended for patients who have not responded to
drugs or cardioversion.

I Art therapy
Definition

Alternative treatment
Since some arrhythmias can be life threatening, a
conventional medical doctor should always be consulted first. Acupuncture can correct an insignificant
number (1.5%) of atrial fibrillation cases. For new,
minor arrhythmias, acupuncture may be effective in
up to 70% of cases, but this figure may not differ
much from placebo therapy. Both western and
Chinese herbal remedies are also used in the treatment of arrhythmias. Since hawthorn (Crataegus laevigata) dilates the blood vessels and stimulates the
heart muscle, it may help to stabilize arrhythmias. It
is gentle and appropriate for home use, unlike foxglove (Digitalis purpurea), an herb whose action on
the heart is too potent for use without supervision by
a qualified practitioner. Homeopathic practitioners
may prescribe remedies such as Lachesis and aconite
or monkshood (Aconitum napellus) to treat mild
arrhythmias.

Art therapy, sometimes called creative arts therapy or expressive arts therapy, encourages people to
express and understand emotions through artistic
expression and through the creative process.

Purpose
Art therapy provides the client-artist with critical
insight into emotions, thoughts, and feelings. Key
benefits of the art therapy process include:


Self-discovery. At its most successful, art therapy
triggers an emotional catharsis.



Personal fulfillment. The creation of a tangible
reward can build confidence and nurture feelings of
self-worth. Personal fulfillment comes from both the
creative and the analytical components of the artistic
process.



Empowerment. Art therapy can help people visually
express emotions and fears that they cannot express
through conventional means, and can give them
some sense of control over these feelings.



Relaxation and stress relief. Chronic stress can be
harmful to both mind and body. Stress can weaken
and damage the immune system, can cause insomnia
and depression, and can trigger circulatory problems
(like high blood pressure and irregular heartbeats).
When used alone or in combination with other
relaxation techniques such as guided imagery, art
therapy can effectively relieve stress.



Symptom relief and physical rehabilitation. Art therapy can also help patients cope with pain. This
therapy can promote physiological healing when
patients identify and work through anger, resentment, and other emotional stressors. It is often
prescribed to accompany pain control therapy for
chronically and terminally ill patients.

Prognosis
Advances in diagnostic techniques, new drugs,
and medical technology have extended the lives of
many patients with serious arrhythmias. Diagnostic
techniques enable physicians to accurately identify
arrhythmias, while new drugs, advances in pacemaker
technology, the development of implantable defibrillators, and progress in ablative techniques offer effective treatments for many types of arrhythmia.

Prevention
Some arrhythmias can be prevented by managing
stress, controlling anxiety, and avoiding caffeine, alcohol, decongestants, cocaine, and cigarettes.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto
GALE ENCYCLOPEDIA OF MEDICINE

Description
Origins
Humans have expressed themselves with symbols
throughout history. Masks, ritual pottery, costumes,
other objects used in rituals, cave drawings, Egyptian
hieroglyphics, and Celtic art and symbols are all visual
records of self-expression and communication
through art. Art has also been associated spiritual
power, and artistic forms such as the Hindu and
399

Art therapy

KEY TERMS
Catharsis—Therapeutic discharge of emotional
tension by recalling past events.
Mandala—A design, usually circular, that appears
in religion and art. In Buddhism and Hinduism, the
mandala has religious ritual purposes and serves as
a yantra (a geometric emblem or instrument of
contemplation).
Organic illness—A physically, biologically based
illness.

Buddhist mandala and Native American sand painting are considered powerful healing tools.
In the late nineteenth century, French psychiatrists Ambrose Tardieu and Paul-Max Simon both
published studies on the similar characteristics of and
symbolism in the artwork of the mentally ill. Tardieu
and Simon viewed art therapy as an effective diagnostic tool to identify specific types of mental illness or
traumatic events. Later, psychologists would use this
diagnostic aspect to develop psychological drawing
tests (the Draw-A-Man test, the Draw-A-Person
Questionnaire [DAP.Q]) and projective personality
tests involving visual symbol recognition (e.g., the
Rorschach Inkblot Test, the Thematic Apperception
Test [TAT], and the Holtzman Inkblot Test [HIT]).
The growing popularity of milieu therapies at
psychiatric institutions in the twentieth century was
an important factor in the development of art therapy
in the United States. Milieu therapies (or environmental therapy) focus on putting the patient in a controlled
therapeutic social setting that provides the patient
with opportunities to gain self-confidence and interact
with peers in a positive way. Activities that encourage
self-discovery and empowerment such as art, music,
dance, and writing are important components of this
approach.
Educator and therapist Margaret Naumburg was
a follower of both Freud and Jung, and incorporated
art into psychotherapy as a means for her patients to
visualize and recognize the unconscious. She founded
the Walden School in 1915, where she used students’
artworks in psychological counseling. She published
extensively on the subject and taught seminars on the
technique at New York University in the 1950s.
Today, she is considered the founder of art therapy
in the United States.
400

In the 1930s, Karl, William, and Charles Menninger
introduced an art therapy program at their Kansasbased psychiatric hospital, the Menninger Clinic. The
Menninger Clinic employed a number of artists in residence in the following years, and the facility was also
considered a leader in the art therapy movement
through the 1950s and 60s. Other noted art therapy
pioneers who emerged in the 50s and 60s include Edith
Kramer, Hanna Yaxa Kwiatkowska (National Institute
of Mental Health), and Janie Rhyne.
Art therapy, sometimes called expressive art or art
psychology, encourages self-discovery and emotional
growth. It is a two part process, involving both the
creation of art and the discovery of its meaning.
Rooted in Freud and Jung’s theories of the subconscious and unconscious, art therapy is based on the
assumption that visual symbols and images are the
most accessible and natural form of communication
to the human experience. Patients are encouraged to
visualize, and then create, the thoughts and emotions
that they cannot talk about. The resulting artwork is
then reviewed and its meaning interpreted by the
patient.
The ‘‘analysis’’ of the artwork produced in art
therapy typically allows patients to gain some level of
insight into their feelings and lets them to work
through these issues in a constructive manner. Art
therapy is typically practiced with individual, group,
or family psychotherapy (talk therapy). While a therapist may provide critical guidance for these activities, a
key feature of effective art therapy is that the patient/
artist, not the therapist, directs the interpretation of
the artwork.
Art therapy can be a particularly useful treatment
tool for children, who frequently have limited language skills. By drawing or using other visual means
to express troublesome feelings, younger patients
can begin to address these issues, even if they cannot
identify or label these emotions with words. Art
therapy is also valuable for adolescents and adults
who are unable or unwilling to talk about thoughts
and feelings.
Beyond its use in mental health treatment, art
therapy is also used with traditional medicine to
treat organic diseases and conditions. The connection between mental and physical health is well
documented, and art therapy can promote healing
by relieving stress and allowing the patient to
develop coping skills.
Art therapy has traditionally centered on visual
mediums, like paintings, sculptures, and drawings.
Some mental healthcare providers have now
GALE ENCYCLOPEDIA OF MEDICINE

Art therapy is often one part of a psychiatric
inpatient or outpatient treatment program, and can
take place in individual or group therapy sessions.
Group art therapy sessions often take place in
hospital, clinic, shelter, and community program
settings. These group therapy sessions can have
the added benefits of positive social interaction,
empathy, and support from peers. The client-artist
can learn that others have similar concerns and
issues.

Preparations
Before starting art therapy, the therapist may
have an introductory session with the client-artist to
discuss art therapy techniques and give the client the
opportunity to ask questions about the process. The
client-artist’s comfort with the artistic process is critical to successful art therapy.
The therapist ensures that appropriate materials
and space are available for the client-artist, as well as
an adequate amount of time for the session. If the
individual artist is exploring art as therapy without
the guidance of a trained therapist, adequate materials, space, and time are still important factors in a
successful creative experience.
The supplies used in art therapy are limited only
by the artist’s (and/or therapist’s) imagination. Some
of the materials often used include paper, canvas,
poster board, assorted paints, inks, markers, pencils,
charcoals, chalks, fabrics, string, adhesives, clay,
wood, glazes, wire, bendable metals, and natural
items (like shells, leaves, etc.). Providing artists with
a variety of materials in assorted colors and textures
can enhance their interest in the process and may
result in a richer, more diverse exploration of their
emotions in the resulting artwork. Appropriate tools
such as scissors, brushes, erasers, easels, supply trays,
glue guns, smocks or aprons, and cleaning materials
are also essential.
An appropriate workspace should be available for
the creation of art. Ideally, this should be a bright,
quiet, comfortable place, with large tables, counters,
or other suitable surfaces. The space can be as simple
as a kitchen or office table, or as fancy as a specialized
artist’s studio.
The artist should have adequate time to become
comfortable with and explore the creative process.
This is especially true for people who do not consider
themselves ‘‘artists’’ and may be uncomfortable with
GALE ENCYCLOPEDIA OF MEDICINE

the concept. If performed in a therapy group or oneon-one session, the art therapist should be available to
answer general questions about materials and/or the
creative process. However, the therapist should be
careful not to influence the creation or interpretation
of the work.

Precautions
Art materials and techniques should match the
age and ability of the client. People with impairments,
such as traumatic brain injury or an organic neurological condition, may have difficulties with the selfdiscovery portion of the art therapy process depending
on their level of functioning. However, they may still
benefit from art therapy through the sensory stimulation it provides and the pleasure they get from artistic
creation.
While art is accessible to all (with or without a
therapist to guide the process), it may be difficult to
tap the full potential of the interpretive part of art
therapy without a therapist to guide the process.
When art therapy is chosen as a therapeutic tool
to cope with a physical condition, it should be
treated as a supplemental therapy and not as a
substitute for conventional medical treatments.

Research and general acceptance
A wide body of literature supports the use of art
therapy in a mental health capacity. And as the mindbody connection between psychological well-being
and physical health is further documented by studies
in the field, art therapy gains greater acceptance by
mainstream medicine as a therapeutic technique for
organic illness.
Resources
BOOKS

Ganim, Barbara. Art and Healing: Using expressive art
toheal your body, mind, and spirit. New York: Three
Rivers Press, 1999.
ORGANIZATIONS

American Art Therapy Association.1202 Allanson Rd.,
Mundelein, IL 60060-3808. 888-290-0878 or 847-9496064. Fax: 847-566-4580. E-mail: arttherapy@ntr.net
<http://www.arttherapy.org>.

Paula Anne Ford-Martin

Arterial blood gas analysis see Blood gas
analysis
401

Art therapy

broadened the definition to include music, film, dance,
writing, and other types of artistic expression.

Arterial embolism

I Arterial embolism

KEY TERMS

Definition

Atrial fibrillation—An arrhythmia; chaotic quivering of the arteries.
Thrombosis—A blockage in a blood vessel that
builds and remains in one place.

An embolus is a blood clot, bit of tissue or
tumor, gas bubble, or other foreign body that circulates in the blood stream until it becomes stuck in
a blood vessel.

Description
When a blood clot develops in an artery and
remains in place, it is called a thrombosis. If all or
part of the blockage breaks away and lodges in
another part of the artery, it is called an embolism.
Blockage of an artery in this manner can be the result
of a blood clot, fat cells, or an air bubble.

Diagnosis
The following tests can be used to confirm the
presence of an arterial embolism:


Electrocardiogram, also known as an EKG or ECG.
For this test, patches that detect electrical impulses
from the heart are attached to the chest and extremities. The information is displayed on a monitor
screen or a paper tape in the form of waves.
Reduced blood and oxygen supply to the heart
shows as a change in the shape of the waves.



Noninvasive vascular tests. These involve measuring
blood pressure in various parts of the body and
comparing the results from each location. When
there is a decrease in blood pressure beyond what is
normal between two points, a blockage is presumed
to be present.



Angiography. In this procedure, a colored liquid
material (a dye, or contrast material) that can be
seen with x rays is injected into the blood stream
through a small tube called a catheter. As the dye
fills the arteries, they are easily seen on x ray motion
pictures. If there is a blockage in the artery, it shows
up as a sudden cut off in the movement of contrast
material. Angiography is an expensive procedure
and does carry some risk. The catheter may cause
a blood clot to form, blocking blood flow. There is
also the risk of poking the catheter through the artery
or heart muscle. Some people may be allergic to the
dye. The risk of any of these injuries occurring is
small.

When an embolus blocks the flow of blood
in an artery, the tissues beyond the plug are
deprived of normal blood flow and oxygen. This
can cause severe damage and even death of the
tissues involved.
Emboli can affect any part of the body. The most
common sites are the legs and feet. When the brain is
affected, it is called a stroke. When the heart is
involved, it is called a heart attack or myocardial
infarction (MI).

Causes and symptoms
A common cause of embolus is when an artery
whose lining has become thickened or damaged,
usually with age, allows cholesterol to build up
more easily than normal on the artery wall. If
some of the cholesterol breaks off, it forms an
embolus. Emboli also commonly form from blood
clots in a heart that has been damaged from heart
attack or when the heart contracts abnormally from
atrial fibrillation.
Other known causes are fat cells that enter the
blood after a major bone fracture, infected blood
cells, cancer cells that enter the blood stream, and
small gas bubbles.
Symptoms of an embolus can begin suddenly or
build slowly over time, depending on the amount of
blocked blood flow.
If the embolus is in an arm or leg, there will be
muscle pain, numbness or tingling, pale skin color,
lower temperature in the limb, and weakness or loss
of muscle function. If it occurs in an internal organ,
there is usually pain and/or loss of the organ’s
function.
402

Treatment
Arterial embolism can be treated with medication
or surgery, depending on the extent and location of the
blockage.
Medication to dissolve the clot is usually given
through a catheter directly into the affected artery. If
the embolus was caused by a blood clot, medications
that thin the blood will help reduce the risk of another
embolism.
GALE ENCYCLOPEDIA OF MEDICINE

If the condition is severe, a surgeon may elect to
bypass the blocked vessel by grafting a new vessel in its
place.

Prognosis
An arterial embolism is serious and should be
treated promptly to avoid permanent damage to the
affected area. The outcome of any treatment depends
on the location and seriousness of the embolism. New
arterial emboli can form even after successful treatment of the first event.

Prevention
Prevention may include diet changes to reduce
cholesterol levels, medications to thin the blood, and
practicing an active, healthy lifestyle.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
OTHER

‘‘Arterial Embolism.’’ HealthAnswers.com. <http://
www.healthanswers.com>.

Dorothy Elinor Stonely

Arteriogram see Angiography
Arteriography see Angiography
Arteriosclerosis see Atherosclerosis

I

Following the release of oxygen in the tissues, the
blood returns to the heart in veins. An arteriovenous
fistula is an abnormal connection of an artery and a
vein. The blood bypasses the capillaries and tissues, and
returns to the heart. Arterial blood has a higher blood
pressure than veins and causes swelling of veins
involved in a fistula. Although both the artery and the
vein retain their normal connections, the new opening
between the two will cause some arterial blood to shunt
into the vein because of the blood pressure difference.

Causes and symptoms
There are two types of arteriovenous fistulas, congenital and acquired. A congenital arteriovenous fistula is one that formed during fetal development. It is a
birth defect. In congenital fistulas, blood vessels of the
lower extremity are more frequently involved than
other areas of the body. Congenital fistulas are not
common. An acquired arteriovenous fistula is one that
develops after a person is born. It usually occurs when
an artery and vein that are side-by-side are damaged
and the healing process results in the two becoming
linked. After catheterizations, arteriovenous fistulas
may occur as a complication of the arterial puncture
in the leg or arm. Fistulas also form without apparent
cause. In the case of patients on hemodialysis, physicians perform surgery to create a fistula. These
patients receive many needle sticks to flush their
blood through dialysis machines and for routine
blood analysis testing. The veins used may scar and
become difficult to use. Surgery is used to connect an
artery and vein so that arterial blood pressure and flow
rate widens the vein and decreases the chance of blood
clots forming inside the vein.
The main symptoms of arteriovenous fistulas near
the surface of the skin are bulging and discolored
veins. In some cases, the bulging veins can be mistaken
for varicose veins. Other fistulas can cause more serious problems depending on their location and the
blood vessels involved.

Diagnosis

Arteriovenous fistula

Definition
An arteriovenous fistula is an abnormal channel
or passage between an artery and a vein.

Using a stethoscope, a physician can detect the
sound of a pulse in the affected vein (bruit). The sound
is a distinctive to-and-fro sound. Dye into the blood can
be tracked by x ray to confirm the presence of a fistula.

Treatment
Description
An arteriovenous fistula is a disruption of the normal blood flow pattern. Normally, oxygenated blood
flows to the tissue through arteries and capillaries.
GALE ENCYCLOPEDIA OF MEDICINE

Small arteriovenous fistulas can be corrected by
surgery. Fistulas in the brain or eye are very difficult to
treat. If surgery is not possible or very difficult, injection therapy may be used. Injection therapy is the
403

Arteriovenous fistula

A surgeon can remove an embolus by making an
incision in the artery above the blockage and, using a
catheter inserted past the embolus, drag it out through
the incision.

Arteriovenous malformations

KEY TERMS
Congenital—Present at the time of birth.

injection of substances that cause the blood to clot at
the site of the injection. In the case of an arteriovenous
fistula, the blood clot should stop the passage of blood
from the artery to the vein. Surgery is usually used to
correct acquired fistulas once they are diagnosed.
Resources
BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, eds. The
Heart. 9th ed. New York: McGraw-Hill, 1998.
Berkow, Robert, ed. Merck Manual of Medical Information.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Braunwald, E. Heart Disease. Philadelphia: W. B. Saunders
Co., 1997.

John T. Lohr, PhD

I Arteriovenous malformations
Definition
Arteriovenous malformations are blood vessel
defects that occur before birth when the fetus is growing in the uterus (prenatal development). The blood
vessels appear as a tangled mass of arteries and veins.
They do not possess the capillary (very fine blood
vessels) bed which normally exists in the common
area where the arteries and veins lie in close proximity
(artery-vein interface). An arteriovenous malformation (AVM) may hemorrhage, or bleed, leading to
serious complications that can be life-threatening.

Description
AVMs represent an abnormal interface between
arteries and veins. Normally, arteries carry oxygenated blood to the body’s tissues through progressively smaller blood vessels. The smallest are
capillaries, which form a web of blood vessels (the
capillary bed) through the body’s tissues. The arterial
blood moves through tissues by these tiny pathways,
exchanging its load of oxygen and nutrients for carbon
dioxide and other waste products produced by the
body cells (cellular wastes). The blood is carried
404

Arteriovenous malformations. (Custom Medical Stock Photo.
Reproduced by permission.)

away by progressively larger blood vessels, the veins.
AVMs lack a capillary bed and arterial blood is moved
(shunted) directly from the arteries into the veins.
AVMs can occur anywhere in the body and have
been found in the arms, hands, legs, feet, lungs, heart,
liver, and kidneys. However, 50% of these malformations are located in the brain, brainstem, and spinal
cord. Owing to the possibility of hemorrhaging, such
AVMs carry the risk of stroke, paralysis, and the loss
of speech, memory, or vision. An AVM that hemorrhages can be fatal.
Approximately three of every 100,000 people have
a cerebral AVM and roughly 40-80% of them will
experience some bleeding from the abnormal blood
vessels at some point. The annual risk of an AVM
bleeding is estimated at about 1-4%. After age 55, the
risk of bleeding decreases. Pre-existing high blood pressure or intense physical activity do not seem to be
associated with AVM hemorrhage, but pregnancy and
labor could cause a rupture or breaking open of a blood
vessel. An AVM hemorrhage is not as dangerous as an
aneurysmal rupture. (An aneurysm is a swollen, blood
filled vessel where the pressure of the blood causes the
wall to bulge outward.) There is an approximate 10%
fatality rate associated with AVM hemorrhage, compared to a 50% fatality rate for ruptured aneurysms.
Although AVMs are congenital defects, meaning
a person is born with them, they are rarely discovered
before age 20. A genetic link has been proposed for
some AVMs, but studies are only suggestive, not positive. The majority of AVMs are discovered in people
age 20-40. Medical researchers estimate that the malformations are created during days 45-60 of fetal
development. A second theory suggests that AVMs
are primitive structures that are left over from the
GALE ENCYCLOPEDIA OF MEDICINE

Aneurysm—A weak point in a blood vessel where
the pressure of the blood causes the vessel wall to
bulge outwards.
Angiography—A mapping of the brain’s blood
vessels, using x-ray imaging.
Capillary bed—A dense network of tiny blood vessels that enables blood to fill a tissue or organ.
Hydrocephalus—Swelling of the brain caused by
an accumulation of fluid.
Lumbar puncture—A diagnostic procedure in
which a needle is inserted into the lower spine to
withdraw a small amount of cerebrospinal fluid.
This fluid is examined to assess trauma to the brain.
Saccular aneurysm—A type of aneurysm that
resembles a small sack of blood attached to the
outer surface of a blood vessel by a thin neck.

period when fetal blood circulating systems began to
develop.
However they form, AVMs have blood vessels
that are abnormally fragile. The arteries that feed
into the malformation are unusually swollen and thin
walled. They lack the usual amount of smooth muscle
tissue and elastin, a fibrous connective tissue. These
blood vessels commonly accumulate deposits of calcium salts and hyalin. The venous part of the malformation receives blood directly from the artery.
Without the intervening capillary bed, the veins
receive blood at a higher pressure than they were
designed to handle. This part of the malformation is
also swollen (dilated) and thin walled. There is a measurable risk of an aneurysm forming near an AVM,
increasing the threat of hemorrhage, brain damage,
and death. Approximately 10-15% of AVMs are
accompanied by saccular aneurysms, a type of aneurysm that looks like a small sac attached to the outer
wall of the blood vessel.
Although the malformation itself lacks capillaries,
there is often an abnormal proliferation of capillaries
next to the defect. These blood vessels feed into the
malformation, causing it to grow larger in some cases.
As the AVM receives more blood through this ‘‘steal,’’
adjacent brain tissue does not receive enough. These
areas show abnormal nerve cell growth, cell death,
and deposits of calcium in that area (calcification).
Nerve cells within the malformation may demonstrate abnormal growth and are believed to be
nonfunctional.
GALE ENCYCLOPEDIA OF MEDICINE

Most people do not realize that they have an
AVM unless it hemorrhages enough to produce symptoms. Small AVMs are more likely to hemorrhage. If a
hemorrhage occurs, it produces a sudden, severe headache. The headache may be focused in one specific
area or it may be more general. It can be mistaken
for a migraine in some cases. The headache is accompanied by other symptoms, such as vomiting, a stiff
neck, sleepiness, lethargy, confusion, irritability, or
weakness anywhere in the body. Seizures occur in
about a quarter of AVM cases. A person may experience decreased, double, or blurred vision.
Hemorrhaging from an AVM is generally less dangerous than hemorrhaging from an aneurysm, with a
survival rate of 80-90%.
Other symptoms occur less frequently, but sometimes appear alongside major symptoms such as the
sudden severe headache. Additional warning signs of a
bleeding AVM are impaired speech or smell, fainting,
facial paralysis, a drooping eyelid, dizziness, and ringing or buzzing in the ears.
Although large AVMs are less likely to hemorrhage, they can induce symptoms based on their mass
alone. Large AVMs exert pressure against brain tissue,
cause abnormal development in the surrounding brain
tissue, and slow down or block blood flow.
Hydrocephalus, a swelling of brain tissue caused by
accumulated fluids, may develop. The warning signs
associated with a large non-bleeding AVM are similar
to the symptoms of a small malformation that is bleeding. Unexplained headaches, seizures, dizziness, and
neurological symptoms, such as sensory changes, are
signals that demand medical attention.

Diagnosis
Based on the clinical symptoms such as severe
headache and neurological problems, and after a complete neurologic exam, a computed tomography scan
(CT) of the head will be done. In some cases, a
whooshing sound from arteries in the neck or over
the eye or jaw (called a bruit), can be heard with a
stethoscope. The CT scan will reveal whether there has
been bleeding in the brain and can identify AVMs
larger than 1 inch (2.5 cm). Magnetic resonance imaging (MRI) is also used to identify an AVM. A lumbar
puncture, or spinal tap, may follow the MRI or CT
scan. A lumbar puncture involves removing a small
amount of cerebrospinal fluid from the lower part of
the spine. Blood cells or blood breakdown products in
the cerebrospinal fluid indicate bleeding.
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Arteriovenous malformations

Causes and symptoms

KEY TERMS

Arteriovenous malformations

To pinpoint where the blood is coming from, a
cerebral angiography is done. This procedure uses
x rays to map out the blood vessels in the brain,
including the vessels that feed into the malformation.
The information gained from angiography complements the MRI and helps distinguish the precise
location of the AVM.

Treatment
Neurosurgeons consider several factors before
deciding on a treatment option. There is some debate
over whether or not to treat AVMs that have not
ruptured and are not causing any symptoms. The
risks and benefits of proceeding with treatment need
to be measured on an individual basis, taking into
account factors such as the person’s age and general
health, as well as the AVM’s size and location. Several
treatment options are available, both for symptomatic
or asymptomatic AVMs. These treatment options
may be used alone or in combination.
Surgery
Removing the AVM is the surest way of preventing
it from causing future problems. Both small and large
AVMs can be handled in surgery. Surgery is recommended for superficial AVMs, but may be too dangerous for deep or very large AVMs. Unless it is
an emergency situation, an AVM that has hemorrhaged
is treated conservatively for several weeks. Conservative
treatment consists of managing the immediate symptoms and allowing the patient’s condition to stabilize.
Surgery requires general anesthesia and a longer period
of recuperation than any other treatment option.
Radiation
Radiation is particularly useful to treat small
(under 1 in) malformations that are deep within the
brain. Ionizing radiation is directed at the malformation, destroying the AVM without damaging the surrounding tissue. Radiation treatment is accomplished
in a single session and it is not necessary to open the
skull. However, success can only be measured over
the course of the following two years. A year after
the procedure, 50-75% of treated AVMs are completely blocked; two years after radiation treatment, the
percentage increases to 85-95%.
Embolization
Embolization involves plugging up access to the
malformation. This technique does not require opening the skull to expose the brain and can be used to
406

treat deep AVMs. Using x-ray images as a guide, a
catheter is threaded through the artery in the thigh
(femoral artery) to the affected area. The patient
remains awake during the procedure and medications
can be administered to prevent discomfort. The blood
vessel leading into the AVM is assessed for its importance to the rest of the brain before a balloon or other
blocking agent is inserted via the catheter. The block
chokes off the blood supply to the malformation.
There may be a mild headache or nausea associated
with the procedure, but patients may resume normal
activities after leaving the hospital. At least two to
three embolization procedures are usually necessary
at intervals of two to six weeks. At least a three-day
hospital stay is associated with each embolization.

Prognosis
Approximately 10% of AVM cases are fatal.
Seizures and neurological changes may be permanent
in another 10-30% cases of AVM rupture. If an AVM
bleeds once, it is about 20% likely to bleed again in the
next year. As time passes from the initial hemorrhage,
the risk for further bleeding drops to about 3-4%. If
the AVM has not bled, it is possible, but not guaranteed, that it never will. Untreated AVMs can grow
larger over time and rarely go away by themselves.
Once an AVM is removed and a person has recovered
from the procedure, there should be no further symptoms associated with that malformation.
Resources
PERIODICALS

Henning, Mast. ‘‘Risk of Spontaneous Hemorrhage after
Diagnosis of Cerebral Arteriovenous Malformation.’’
The Lancet 350 (October 11, 1997): 1065.
ORGANIZATIONS

American Chronic Pain Association. PO Box 850, Rocklin,
CA 95677-0850. (916) 632-0922. <http://members.
tripod.com/widdy/ACPA.html>.
Arteriovenous Malformation Support Group. 168
Six Mile Canyon Road, Dayton, NV 89403. (702)
246-0682.
National Chronic Pain Outreach Association, Inc. P.O. Box
274, Millboro, VA 24460. (540) 997-5004.

Julia Barrett

Arthritis see Juvenile arthritis;
Osteoarthritis; Psoriatic arthritis;
Rheumatoid arthritis
Arthrocentesis see Joint fluid analysis
Arthrogram see Arthrography
GALE ENCYCLOPEDIA OF MEDICINE

Arthrography

I Arthrography
Definition
Arthrograpy is a procedure involving multiple
x rays of a joint using a fluoroscope, or a special
piece of x-ray equipment which shows an immediate
x-ray image. A contrast medium (in this case, a contrast iodine solution) injected into the joint area helps
highlight structures of the joint.

Purpose
Frequently, arthrography is ordered to determine
the cause of unexplained joint pain. This fluoroscopic
procedure can show the internal workings of specific
joints and outline soft tissue structures. The procedure
may also be conducted to identify problems with the
ligaments, cartilage, tendons, or the joint capsule of
the hip, shoulder, knee, ankle or wrist. An arthrography procedure may locate cysts in the joint area, evaluate problems with the joint’s arrangement and
function, or indicate the need for joint replacement
(prostheses). The most commonly studied joints are
the knee and shoulder.

Precautions
Patients who are pregnant or may be pregnant
should not have this procedure unless the benefits of
the findings outweigh the risk of radiation exposure.
Patients who are known to be allergic to iodine need to
discuss this complication with their physician. Patients
who have a known allergy to shellfish are more likely
to be allergic to iodine contrast.

Description
Arthrograpy may be referred to as ‘‘joint radiography’’ or ‘‘x rays of the joint.’’ The term arthrogram
may be used interchangeably with arthrography. The
joint area will be cleaned and a local anesthetic
will be injected into the tissues around the joint
to reduce pain. Next, if fluids are present in the
joint, the physician may suction them out (aspirate) with a needle. These fluids may be sent to a
laboratory for further study. Contrast agents are
then injected into the joint through the same location by attaching the aspirating needle to a syringe
containing the contrast medium. The purpose of
contrast agents in x-ray procedures is to help highlight details of areas under study by making them
opaque. Agents for arthrography are generally air
and water-soluble dyes, the most common
GALE ENCYCLOPEDIA OF MEDICINE

An x-ray image of the knees of a patient with cysts caused by
rheumatoid arthritis. The cysts appear as dark areas just
below the knee joints. (Custom Medical Stock Photo.
Reproduced by permission.)

KEY TERMS
Aspirate—Remove fluids by suction, often through
a needle.
Contrast (agent, medium)—A substance injected
into the body that illuminates certain structures
that would otherwise be hard to see on the radiograph (film).
Fluoroscope—A device used in some radiology
procedures that provides immediate images and
motion on a screen much like those seen at airport
baggage security stations.
Radiologist—A medical doctor specially trained in
radiology (x ray) interpretation and its use in the
diagnosis of diseases and injuries.
X ray—A form of electromagnetic radiation with
shorter wavelengths than normal light. X rays can
penetrate most structures.

containing iodine. Air and iodine may be used
together or independently. After the contrast
agent is administered, the site of injection will be
sealed and the patient may be asked to move the
joint around to distribute the contrast.
Before the contrast medium can be absorbed by
the joint itself, several films will be quickly taken
under the guidance of the fluoroscope. The patient
will be asked to move the joint into a series of
positions, keeping still between positioning.
Sometimes, the patient will experience some tingling
or discomfort during the procedure, which is
407

Arthroplasty

normal and due to the contrast. Following fluoroscopic tracking of the contrast, standard x rays of
the area may also be taken. The entire procedure
will last about one hour.

Preparation
It is important to discuss any known sensitivity to
local anesthetics or iodine prior to this procedure. A
physician should explain the procedure and the risks
associated with contrast agents and ask the patient to
sign an informed consent. If iodine contrast will be
administered, the patient may be instructed not to eat
before the exam. The timeframe of fasting may extend
from only 90 minutes prior to the exam up to the night
before. There is no other preparation necessary.

of the rotator cuff, tears in the ligament and other
conditions. The entire lining of the joint becomes opaque from the technique, which allows the radiologist
to see abnormalities in the intricate workings of the
joint. In the case of recurrent shoulder dislocations,
arthrography results can be used to evaluate damage.
Patients with hip prostheses may receive arthrography
to evaluate proper placement or function of their
prostheses.
Resources
ORGANIZATIONS

American College of Radiology. 1891 Preston White Drive,
Reston, VA 22091. (800) 227-5463. <http://
www.acr.org>.
Arthritis Foundation. 1300 W. Peachtree St., Atlanta, GA
30309. (800) 283-7800. <http://www.arthritis.org>.

Aftercare
The affected joint should be rested for approximately 12 hours following the procedure. The joint
may be wrapped in an elastic bandage and the patient
should receive instructions on the care and changing of
the bandage. Noises in the joint such as cracking
or clicking are normal for a few days following arthrography. These noises are the result of liquid in the joints.
Swelling may also occur and can be treated with application of ice or cold packs. A mild pain reliever can be
used to lessen pain in the first few days. However, if any
of these symptoms persist for more than a few days,
patients are advised to contact their physician.

Risks
In some patients iodine can cause allergic reactions,
ranging from mild nausea to severe cardiovascular or
nervous system complications. Since the contrast dye is
put into a joint, rather than into a vein, allergic reactions
are rare. Facilities licensed to perform contrast exams
should meet requirements for equipment, supplies and
staff training to handle a possible severe reaction.
Infection or joint damage are possible, although not
frequent, complications of arthrography.

Normal results
A normal arthrography exam will show proper placement of the dye or contrast medium throughout the
joint structures, joint space, cartilage and ligaments.

Abnormal results
The abnormal placement of dye may indicate
rheumatoid arthritis, cysts, joint dislocation, rupture
408

Teresa Odle

I Arthroplasty
Definition
Arthroplasty is surgery to relieve pain and restore
range of motion by realigning or reconstructing a joint.

Purpose
The goal of arthroplasty is to restore the function
of a stiffened joint and relieve pain. Two types of
arthroplastic surgery exist. Joint resection involves
removing a portion of the bone from a stiffened
joint, creating a gap between the bone and the socket,
to improve the range of motion. Scar tissue eventually
fills the gap. Pain is relieved and motion is restored,
but the joint is less stable.
Interpositional reconstruction is surgery to
reshape the joint and add a prosthetic disk between
the two bones forming the joint. The prosthesis can
be made of plastic and metal or from body tissue
such as fascia and skin. When interpositional
reconstruction fails, total joint replacement may be
necessary. Joint replacement is also called total
joint arthroplasty.
In recent years, joint replacement has become the
operation of choice for most knee and hip problems.
Elbow, shoulder, ankle, and finger joints are more
likely to be treated with joint resection or interpositional reconstruction.
GALE ENCYCLOPEDIA OF MEDICINE

Fascia—Thin connective tissue covering or separating the muscles and internal organs of the
body.
Rheumatoid arthritis—A joint disease of
unknown origins that may begin at an early age,
causing deformity and loss of function in the
joints.

Arthroplasty is performed on people suffering
from severe pain and disabling joint stiffness that
result from osteoarthritis or rheumatoid arthritis.
Joint resection, rather than joint replacement, is
more likely to be performed on people with rheumatoid arthritis, especially when the elbow joint is
involved. Total joint replacement is usually reserved
for people over the age of 60.

Patients who have undergone arthroplasty must
be careful not to over stress or destabilize the joint.
Physical therapy is begun immediately. Antibiotics are
given to prevent infection.

Risks
Joint resection and interpositional reconstruction
do not always produce successful results, especially in
patients with rheumatoid arthritis. Repeat surgery or
total joint replacement may be necessary. As with any
major surgery, there is always a risk of an allergic
reaction to anesthesia or that blood clots will break
loose and obstruct the arteries.

Normal results
Most patients recover with improved range of
motion in the joint and relief from pain.
Resources
BOOKS

Precautions
If both the bone and socket of a joint are
damaged, joint replacement is usually the preferred
treatment.

Description

‘‘Joint Replacement.’’ In Everything You Need to Know
About Medical Treatments. Springhouse, PA:
Springhouse Corp., 1996.
OTHER

‘‘Darrach’s Procedure.’’ Wheeless’ Textbook of Orthopaedics
Page. <http://www.medmedia.com/ooa1/119.htm>.

Tish Davidson, A.M.

Arthroplasty is performed under general or regional anesthesia in a hospital, by an orthopedic surgeon.
Certain medical centers specialize in joint surgery and
tend to have higher success rates than less specialized
centers.
In joint resection, the surgeon makes an incision
at the joint, then carefully removes minimum amount
of bone necessary to allow free motion. The more bone
that remains, the more stable the joint. Ligament
attachments are preserved as much as possible. In
interpositional reconstruction, both bones of the
joint are reshaped, and a disk of material is placed
between the bones to prevent their rubbing together.
Length of hospital stay depends on which joint is
treated, but is normally only a few days.

Preparation
Prior to arthroplasty, all the standard preoperative blood and urine tests are performed. The patient
meets with the anesthesiologist to discuss any
special conditions that affect the administration of
anesthesia.
GALE ENCYCLOPEDIA OF MEDICINE

I Arthroscopic surgery
Definition
Arthroscopic surgery is a procedure to visualize,
diagnose, and treat joint problems. The name is
derived from the Greek words arthron, which means
joint, and skopein, which means to look at.

Purpose
Arthroscopic surgery is used to identify, monitor,
and diagnose joint injuries and disease; or to remove
bone or cartilage or repair tendons or ligaments.
Diagnostic arthroscopic surgery is performed when
medical history, physical exam, x rays, and other
tests such as MRIs or CTs don’t provide a definitive
diagnosis.
409

Arthroscopic surgery

Aftercare

KEY TERMS

Arthroscopic surgery

Telescope

Camera

An arthroscope uses optical fibers to form an image of the damged cartilage, which it sends to a television monitor that helps the
surgeon perform surgery. (Illustration by Argosy Inc.)

Precautions
Diagnostic arthroscopic surgery should not be
performed unless conservative treatment does not fix
the problem.

Description
In arthroscopic surgery, an orthopedic surgeon
uses an arthroscope, a fiber-optic instrument, to see
the inside of a joint. After making an incision about
the size of a buttonhole in the patient’s skin, a sterile
sodium chloride solution is injected to distend the joint.
The arthroscope, an instrument the size of a pencil, is
then inserted into the joint. The arthroscope has a lens
and a lighting system through which the structures
inside the joint are transmitted to a miniature television
camera attached to the end of the arthroscope. The
surgeon uses irrigation and suction to remove blood
and debris from the joint before examining it. Other
incisions may be made in order to see other parts of the
joint or to insert additional instruments. Looking at the
410

interior of the joint on the television screen, the surgeon
can then determine the amount or type of injury and, if
necessary, take a biopsy specimen or repair or correct
the problem. Arthroscopic surgery can be used to
remove floating bits of cartilage and treat minor tears
and other disorders. When the procedure is finished,
the arthroscope is removed and the joint is irrigated.
The site of the incision is bandaged.
Arthroscopic surgery is used to diagnose and treat
joint problems, most commonly in the knee, but also
in the shoulder, elbow, ankle, wrist, and hip. Some of
the most common joint problems seen with an arthroscope are:


inflammation in the knee, shoulder, elbow, wrist, or
ankle



injuries to the shoulder (rotator cuff tendon tears,
impingement syndrome, and recurrent dislocations),
knee (cartilage tears, wearing down of or injury to the
cartilage cushion, and anterior cruciate ligament tears
with instability), and wrist (carpal tunnel syndrome)
GALE ENCYCLOPEDIA OF MEDICINE

Joint—The point where bones meet. Arthroscopic
surgery is used on joint problems.
Laser—A device that concentrates electromagnetic
radiation into a narrow beam and treats tissue
quickly without heating surrounding areas.
Orthopedics—The medical specialty that deals
with preserving, restoring, and developing form
and function in the extremities, spine, and other
structures using medical, surgical, and physical
methods. Arthroscopic surgery is performed by
orthopedic surgeons.



loose bodies of bone and/or cartilage in the knee,
shoulder, elbow, ankle, or wrist

Corrective arthroscopic surgery is performed with
instruments that are inserted through additional incisions. Arthritis can sometimes be treated with arthroscopic surgery. Some problems are treated with a
combination of arthroscopic and standard surgery.
Also called arthroscopy, the procedure is performed
in a hospital or outpatient surgical facility. The type of
anesthesia (local, spinal, or general) and the length of
the procedure depends on the joint operated on and the
complexity of the suspected problem. Arthroscopic surgery rarely takes more than an hour. Most patients who
have arthroscopic surgery are released that same day;
some patients stay in the hospital overnight.
Considered the most important orthopedic development in the 20th century, arthroscopic surgery is
widely used. The use of arthroscopic surgery on famous
athletes has been well publicized. It is estimated that
80% of orthopedic surgeons practice arthroscopic surgery. Arthroscopic surgery was initially a diagnostic
tool used prior to open surgery, but as better instruments and techniques were developed, it began to be
used to actually treat a variety of joint problems. New
techniques currently under development are likely to
lead to other joints being treated with arthroscopic
surgery in the future. Recently, lasers were introduced
in arthroscopic surgery and other new energy sources
are being explored. Lasers and electromagnetic radiation can repair rather than resect injuries and may be
more cost effective than instruments.

Preparation
Before the procedure, blood and urine studies and
x rays of the joint will be conducted.
GALE ENCYCLOPEDIA OF MEDICINE

Immediately after the procedure, the patient will
spend several hours in the recovery room. An ice pack
will be put on the joint that was operated on for up to
48 hours after the procedure. Pain medicine, prescription or non-prescription, will be given. The morning
after the surgery, the dressing can be removed and
replaced by adhesive strips. The patient should call
his/her doctor upon experiencing an increase in pain,
swelling, redness, drainage or bleeding at the site of the
surgery, signs of infection (headache, muscle aches,
dizziness, fever), or nausea or vomiting.
It takes several days for the puncture wounds
to heal, and several weeks for the joint to fully recover.
Many patients can resume their daily activities, including going back to work, within a few days of the
procedure. A rehabilitation program, including physical therapy, may be suggested to speed recovery and
improve the future functioning of the joint.

Risks
Complications are rare in arthroscopic surgery,
occurring in less than 1% of patients. These include
infection and inflammation, blood vessel clots, damage
to blood vessels or nerves, and instrument breakage.
Resources
PERIODICALS

Wilkinson, Todd. ‘‘Pop, Crackle, Snap.’’ Women’s Sports &
Fitness (April 1998): 68.

Lori De Milto

I Arthroscopy
Definition
Arthroscopy is the examination of a joint, specifically, the inside structures. The procedure is performed
by inserting a specifically designed illuminated device
into the joint through a small incision. This instrument
is called an arthroscope. The procedure of arthroscopy
is primarily associated with the process of diagnosis.
However, when actual repair is performed, the procedure is called arthroscopic surgery.

Purpose
Arthroscopy is used primarily by doctors who
specialize in treating disorders of the bones and
411

Arthroscopy

Aftercare

KEY TERMS

Arthroscopy

Arthroscope

Superolateral

Superomedial

Lateral

Medial

Inferolateral

Inferomedial
Central

Common entry sites for the arthroscope

Arthroscopy is primarily used to help diagnose joint problems. This procedure, most commonly associated with knee and
shoulder problems, allows accurate examination and diagnosis of damaged joint ligaments, surfaces, and other related joint
structures. The illustration above indicates the most common entry sites, or portals, in knee arthroscopy. (Illustration by
Electronic Illustrators Group.)

related structures (orthopedics) to help diagnose
joint problems. Once described as essential for those
who primarily care for athletic injuries, arthroscopy
is now a technique commonly used by orthopedic
surgeons for the treatment of patients of all ages.
This procedure is most commonly used to diagnose
knee and shoulder problems, although the elbow,
hip, wrist, and ankle may also be examined with an
arthroscope.
A joint is a complex system. Within a joint, ligaments attach bones to other bones, tendons attach
muscles to bones, cartilage lines and helps protect the

412

ends of bones, and a special fluid (synovial fluid)
cushions and lubricates the structures. Looking inside
the joint allows the doctors to see exactly which structures are damaged. Arthroscopy also permits earlier
diagnosis of many types of joint problems which had
been difficult to detect in previous years.

Precautions
Most arthroscopic procedures today are performed in same-day surgery centers where the patient
is admitted just before surgery. A few hours following
the procedure, the patient is allowed to return home,

GALE ENCYCLOPEDIA OF MEDICINE

Hemarthrosis—A condition of blood within a joint.
Pulmonary embolus—Blockage of an artery of the
lung by foreign matter such as fat, tumor, tissue, or
a clot originating from a vein.
Thrombophlebitis—Inflamation of a vein with the
formation of a thrombus or clot.

although usually someone else must drive. Depending
on the type of anesthesia used, the patient may be told
not to eat for several hours before arriving. Before the
procedure, the anesthesiologist will ask if the patient
has any known allergies to local or general anesthetics.
Airway obstruction is always possible in any patient
who receives a general anesthesia. Because of this,
oxygen, suction, and monitoring equipment must be
available. The patient’s cardiac status should always
be monitored in the event that any cardiac abnormalities arise during the arthroscopy.

Description
The arthroscope is an instrument used to look
directly into the joint. It contains magnifying lenses
and glass-coated fibers that send concentrated light
into the joint. A camera attached to the arthroscope
allows the surgeon to see a clear image of the joint.
This image is then transferred to a monitor located in
the operating room at the time of the arthroscopy.
This video technology is also important for documentation of the arthroscopic procedure. For example, if the surgeon decides after the arthroscopic
examination that a conventional approach to surgically expose or ‘‘open’’ the joint (arthrotomy) must
be used, a good photographic record will be useful
when the surgeon returns to execute the final surgical
plan.
The procedure requires the surgeon to make several small incisions (portals) through the skin’s surface
into the joint. Through one or two of the portals, a
large-bore needle, called a cannula, is attached to tubing and inserted into the joint. The joint is inflated
with a sterile saline solution to expand the joint and
ensure clear arthroscopic viewing. Often, following a
recent traumatic injury to a joint, the joint’s natural
fluid may be cloudy, making interior viewing of the
joint difficult. In this condition, a constant flow of the
saline solution is necessary. This inflow of saline solution may be through the cannula with the outflow
GALE ENCYCLOPEDIA OF MEDICINE

through the arthroscope, or the positions may be
reversed. The arthroscope is placed through one of
the portals to view and evaluate the condition of the
joint.

Preparation
Before an arthroscopy can take place, the surgeon
completes a thorough medical history and evaluation.
Important for the accuracy of this diagnostic
procedure, a medical history and evaluation may discover other disorders of the joint or body parts, proving the procedure unnecessary. This is always
an important preliminary step, because pain can
often be referred to a joint from another area of
the body. Anatomical models and pictures are
useful aids to explain to the patient the proposed
arthroscopy and what the surgeon may be looking at
specifically.
Proper draping of the body part is important to
prevent contamination from instruments used in
arthroscopy, such as the camera, light cords, and
inflow and outflow drains placed in the portals.
Draping packs used in arthroscopy include disposable
paper gowns and drapes with adhesive backing. The
surgeon may also place a tourniquet above the joint to
temporarily block blood flow to the area during the
arthroscopic exam.
General or local anesthesia may be used during
arthroscopy. Local anesthesia is usually used
because it reduces the risk of lung and heart complications and allows the patient to go home sooner.
The local anesthetic may be injected in small
amounts in multiple locations in skin and joint
tissues in a process called infiltration. In other
cases, the anesthetic is injected into the spinal cord
or a main nerve supplying the area. This process is
called a ‘‘block,’’ and it blocks all sensation below
the main trunk of the nerve. For example, a femoral
block anesthetizes the leg from the thigh down (its
name comes from femur, the thighbone). Most
patients are comfortable once the skin, muscles,
and other tissues around the joint are numbed by
the anesthetic; however, some patients are also
given a sedative if they express anxiety about the
procedure. (It’s important for the patient to remain
still during the arthroscopic examination.)
General anesthesia, in which the patient becomes
unconcious, may be used if the procedure may be
unusually complicated or painful. For example,
people who have relatively ‘‘tight’’ joints may be candidates for general anesthesia because the procedure
may take longer and cause more discomfort.
413

Arthroscopy

KEY TERMS

Asbestosis

Aftercare
The portals are closed by small tape strips or
stitches and covered with dressings and a bandage.
The patient spends a short amount of time in the
recovery room after arthroscopy. Most patients can
go home after about an hour in the recovery room.
Pain medication may be prescribed for a short period;
however, many patients find various over-the-counter
pain relievers sufficient.
Following the surgical procedure, the patient
needs to be aware of the signs of infection, which
include redness, warmth, excessive pain, and swelling.
The risk of infection increases if the incisions become
wet too early following surgery. Because of this, it is
good practice to cover the joint with plastic (for example, a plastic bag) while showering after arthroscopy.
The use of crutches is commonplace after arthroscopy, with progression to independent walking on an
‘‘as tolerated’’ basis by the patient. Generally, a rehabilitation program, supervised by a physical therapist,
follows shortly after the arthroscopy to help the
patient regain mobility and strength of the affected
joint and limb.

joint capsule that naturally forms around the joint
becomes thickened, forming adhesions. This results in
a stiff and less mobile joint. This problem is frequently
corrected by manipulation and mobilization of the
joint with the patient placed under general anesthesia.
Resources
PERIODICALS

Glassman, Scott. ‘‘Advances in Treating Shoulder Injuries.’’
Advanced Magazine for Physical Therapists (December
1997): 10-12.

Jeffrey P. Larson, RPT

Artificial insemination see Infertility
therapies

I Asbestosis
Definition
Asbestosis is chronic, progressive inflammation of
the lung. It is not contagious.

Risks
The incidence of complications is low compared
to the high number of arthroscopic procedures performed every year. Possible complications include
infection, swelling, damage to the tissues in the joint,
blood clots in the leg veins (thrombophlebitis), leakage
of blood into the joint (hemarthrosis), blood clots that
move to the lung (pulmonary embolus), and injury to
the nerves around the joint.

Normal results
The goal of arthroscopy is to diagnose a joint
problem causing pain and/or restrictions in normal
joint function. For example, arthroscopy can be a
useful tool in locating a tear in the joint surface of
the knee or locating a torn ligament of the shoulder.
Arthroscopic examination is often followed by arthroscopic surgery performed to repair the problem with
appropriate arthroscopic tools. The final result is to
decrease pain, increase joint mobility, and thereby
improve the overall quality of the patient’s activities
of daily living.

Abnormal results
Less optimal results that may require further treatment include adhesive capsulitis. In this condition, the
414

Description
Asbestosis is a consequence of prolonged exposure to large quantities of asbestos, a material once
widely used in construction, insulation, and manufacturing. When asbestos is inhaled, fibers penetrate the
breathing passages and irritate, fill, inflame, and scar
lung tissue. In advanced asbestosis,, the lungs shrink,
stiffen, and become honeycombed (riddled with tiny
holes).
Legislation has reduced use of asbestos in the
United States, but workers who handle automobile
brake shoe linings, boiler insulation, ceiling acoustic
tiles, electrical equipment, and fire-resistant materials
are still exposed to the substance. Asbestos is used in
the production of paints and plastics. Significant
amounts can be released into the atmosphere when
old buildings or boats are razed or remodeled.
Asbestosis is most common in men over 40 who
have worked in asbestos-related occupations.
Smokers or heavy drinkers have the greatest risk of
developing this disease. Between 1968 and 1992,
more than 10,000 Americans over the age of 15 died
as a result of asbestosis. Nearly 25% of those who
died lived in California or New Jersey, and most of
them had worked in the construction or shipbuilding
trades.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis

Micrograph of asbestos fibers embedded in lung tissue.
(Photograph by Dr. E. Walker, Custom Medical Stock Photo.
Reproduced by permission.)

KEY TERMS
Asbestos—A silicate (containing silica) mineral
that occurs in a variety of forms; it is characterized
by a fibrous structure and resistance to fire.

Causes and symptoms
Occupational exposure is the most common cause
of asbestosis, but the condition also strikes people who
inhale asbestos fiber or who are exposed to waste
products from plants near their homes. Family members can develop the disease as a result of inhaling
particles of asbestos dust that cling to workers’
clothes.
It is rare for asbestosis to develop in anyone who
hasn’t been exposed to large amounts of asbestos on a
regular basis for at least 10 years. Symptoms of the
disease do not usually appear until 15–20 years after
initial exposure to asbestos.
The first symptom of asbestosis is usually shortness of breath following exercise or other physical
activity. The early stages of the disease are also characterized by a dry cough and a generalized feeling of
illness.
As the disease progresses and lung damage
increases, shortness of breath occurs even when
the patient is at rest. Recurrent respiratory infections and coughing up blood are common. So is
swelling of the feet, ankles, or hands. Other symptoms of advanced asbestosis include chest pain,
GALE ENCYCLOPEDIA OF MEDICINE

Screening of at-risk workers can reveal lung
inflammation and lesions characteristic of asbestosis.
Patients’ medical histories can identify occupations,
hobbies, or other situations likely to involve exposure
to asbestos fibers.
X rays can show shadows or spots on the lungs
or an indistinct or shaggy outline of the heart that
suggests the presence of asbestosis. Blood tests are
used to measure concentrations of oxygen and carbon
dioxide. Pulmonary function tests can be used to
assess a patient’s ability to inhale and exhale, and a
computed tomography scan (CT) of the lungs can
show flat, raised patches associated with advanced
asbestosis.

Treatment
The goal of treatment is to help patients breathe
more easily, prevent colds and other respiratory infections, and control complications associated with
advanced disease. Ultrasonic, cool-mist humidifiers
or controlled coughing can loosen bronchial
secretions.
Regular exercise helps maintain and improve lung
capacity. Although temporary bed rest may be recommended, patients are encouraged to resume their regular activities as soon as they can.
Anyone who develops symptoms of asbestosis
should see a family physician or lung disease specialist.
A doctor should be notified if someone who has been
diagnosed with asbestosis:


coughs up blood



continues to lose weight



is short of breath



has chest pain



develops a sudden fever of 1018F (38.38C) or higher



develops unfamiliar, unexplained symptoms

Prognosis
Asbestosis can’t be cured, but its symptoms
can be controlled. Doctors don’t know why the
415

Asbestosis

hoarseness, and restless sleep. Patients who have
asbestosis often have clubbed (widened and thickened) fingers. Other potential complications
include heart failure, collapsed (deflated) lung,
and pleurisy (inflammation of the membrane that
protects the lung).

Ascites

health of some patients deteriorates and the condition of others remain the same, but believe the
difference may be due to varying exposures of
asbestos. People with asbestosis who smoke, particularly those who smoke more than one pack of
cigarettes each day, are at increased risk for developing lung cancer and should be strongly advised
to quit smoking.

Prevention
Workers in asbestosis-related industries should
have regular x rays to determine whether their
lungs are healthy. A person whose lung x ray
shows a shadow should eliminate asbestos exposure even if no symptoms of the condition have
appeared.
Anyone who works with asbestos should wear a
protective mask or a hood with a clean-air supply and
obey recommended procedures to control asbestos
dust. Anyone who is at risk of developing asbestosis
should:


not smoke



be vaccinated against influenza and pneumonia



exercise regularly to maintain cardiopulmonary
fitness



avoid crowds and people who have respiratory
infections

A person who has asbestosis should exercise
regularly, relax, and conserve energy whenever
necessary.
Resources
BOOKS

Burton, George G., John E. Hodgkin, and Jeffrey J. Ward,
editors. Respiratory Care: A Guide to Clinical Practice.
4th ed. Philadelphia: Lippincott, 1997.
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.

Maureen Haggerty

Ascariasis see Roundworm infections
Ascending cholangitis see Cholangitis
Ascending contrast phlebography see
Venography
416

I Ascites
Definition
Ascites is an abnormal accumulation of fluid in
the abdomen.

Description
Rapidly developing (acute) ascites can occur as a
complication of trauma, perforated ulcer, appendicitis, or inflammation of the colon or other tube-shaped
organ (diverticulitis). This condition can also develop
when intestinal fluids, bile, pancreatic juices, or bacteria
invade or inflame the smooth, transparent membrane
that lines the inside of the abdomen (peritoneum).
However, ascites is more often associated with liver
disease and other long-lasting (chronic) conditions.
Types of ascites
Cirrhosis, which is responsible for 80% of all
instances of ascities in the United States, triggers a
series of disease-producing changes that weaken the
kidney’s ability to excrete sodium in the urine.
Pancreatic ascites develops when a cyst that has
thick, fibrous walls (pseudocyst) bursts and permits
pancreatic juices to enter the abdominal cavity.
Chylous ascites has a milky appearance caused by
lymph that has leaked into the abdominal cavity.
Although chylous ascites is sometimes caused by
trauma, abdominal surgery, tuberculosis, or another
peritoneal infection, it is usually a symptom of lymphoma or some other cancer.
Cancer causes 10% of all instances of ascites in the
United States. It is most commonly a consequence of
disease that originates in the peritoneum (peritoneal
carcinomatosis) or of cancer that spreads (metastasizes) from another part of the body.
Endocrine and renal ascites are rare disorders.
Endocrine ascites, sometimes a symptom of an endocrine system disorder, also affects women who are
taking fertility drugs. Renal ascites develops when
blood levels of albumin dip below normal. Albumin
is the major protein in blood plasma. It functions to
keep fluid inside the blood vessels.

Causes and symptoms
Causes
The two most important factors in the production
of ascites due to chronic liver disease are:
GALE ENCYCLOPEDIA OF MEDICINE

Low levels of albumin in the blood that cause a
change in the pressure necessary to prevent fluid
exchange (osmotic pressure). This change in pressure
allows fluid to seep out of the blood vessels.



An increase in the pressure within the branches of
the portal vein that run through liver (portal
hypertension). Portal hypertension is caused by
the scarring that occurs in cirrhosis. Blood that
cannot flow through the liver because of the
increased pressure leaks into the abdomen and
causes ascites.

Other conditions that contribute to ascites development include:

A computed tomography (CT) scan of an axial section
through the abdomen, showing ascites. At right is the liver
occupying much of the abdomen; the stomach and spleen are
also seen. Around these organs is fluid giving rise to this
condition. (Custom Medical Stock Photo. Reproduced by
permission.)



hepatitis



heart or kidney failure



inflammation and fibrous hardening of the sac that
contains the heart (constrictive pericarditis)

Persons who have systemic lupus erythematosus
but do not have liver disease or portal hypertension
occasionally develop ascites. Depressed thyroid
activity sometimes causes pronounced ascites, but
inflammation of the pancreas (pancreatitis) rarely
causes significant accumulations of fluid.
Symptoms

KEY TERMS
Computed tomography scan (CT)—An imaging
technique in which cross-sectional x rays of the
body are compiled to create a three-dimensional
image of the body’s internal structures.

Small amounts of fluid in the abdomen do not
usually produce symptoms. Massive accumulations
may cause:


rapid weight gain



abdominal discomfort and distention

Interferon—A protein formed when cells are
exposed to a virus. Interferon causes other noninfected cells to develop translation inhibitory
protein (TIP). TIP blocks viruses from infecting
new cells.



shortness of breath



swollen ankles

Paracentesis—A procedure in which fluid is
drained from a body cavity by means of a catheter
placed through an incision in the skin.
Systemic lupus erythematosus—An inflammatory
disease that affects many body systems, including
the skin, blood vessels, kidneys, and nervous system. It is characterized, in part, by arthritis, skin
rash, weakness, and fatigue.
Ultrasonography—A test using sound waves to
measure blood flow. Gel is applied to a hand-held
transducer that is pressed against the patient’s
body. Images are displayed on a monitor.

Skin stretches tightly across an abdomen that contains large amounts of fluid. The navel bulges or lies
flat, and the fluid makes a dull sound when the doctor
taps the abdomen. Ascitic fluid may cause the flanks
to bulge.

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis

Physical examination generally enables doctors to
distinguish ascities from pregnancy, intestinal gas,
obesity, or ovarian tunors. Ultrasound or computed
tomography scans (CT) can detect even small amounts
of fluid. Laboratory analysis of fluid extracted by
inserting a needle through the abdominal wall (diagnostic paracentesis) can help identify the cause of the
accumulation.
417

Ascites



Aspartate aminotransferase test

Treatment
Reclining minimizes the amount of salt the kidneys absorb, so treatment generally starts with bed rest
and a low-salt diet. Urine-producing drugs (diuretics)
may be prescribed if initial treatment is ineffective.
The weight and urinary output of patients using diuretics must be carefully monitored for signs of :


hypovolemia (massive loss of blood or fluid)



azotemia (abnormally high blood levels of nitrogenbearing materials)



potassium imbalance



high sodium concentration. If the patient consumes
more salt than the kidneys excrete, increased doses of
diuretics should be prescribed

Moderate-to-severe accumulations of fluid are
treated by draining large amounts of fluid (largevolume paracentesis) from the patient’s abdomen.
This procedure is safer than diuretic therapy. It
causes fewer complications and requires a shorter
hospital stay.
Large-volume paracentesis is also the preferred
treatment for massive ascites. Diuretics are sometimes
used to prevent new fluid accumulations, and the procedure may be repeated periodically.

Alternative treatment
Dietary alterations, focused on reducing salt
intake, should be a part of the treatment. In less severe
cases, herbal diuretics like dandelion (Taraxacum officinale) can help eliminate excess fluid and provide
potassium. Potassium-rich foods like low-fat yogurt,
mackerel, cantaloupe, and baked potatoes help balance excess sodium intake.

Prognosis
The prognosis depends upon the condition that is
causing the ascites. Carcinomatous ascites has a very
bad prognosis. However, salt restriction and diuretics
can control ascites caused by liver disease in many cases.
Therapy should also be directed towards the
underlying disease that produces the ascites.
Cirrhosis should be treated by abstinence from alcohol
and appropriate diet. The new interferon agents
maybe helpful in treating chronic hepatitis.

Prevention
Modifying or restricting use of salt can prevent
most cases of recurrent ascites.
418

Resources
BOOKS

Berkow, Robert, editor. The Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 1997.
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
OTHER

‘‘Hepatic and Liver Disorders.’’ The Meck Page. April 20,
1998. <http://www.merck.com>.

Maureen Haggerty

Ascorbic acid deficiency see Scurvy
ASD see Atrial septal defect
Asian American health see Minority health
Asian flu see Influenza

I Aspartate aminotransferase test
Definition
The Aspartate aminotransferase test measures
levels of AST, an enzyme released into the blood
when certain organs or tissues, particularly the liver
and heart, are injured. Aspartate aminotransferase
(AST) is also known as serum glutamic oxaloacetic
transaminase (SGOT).

Purpose
The determination of AST levels aids primarily in
the diagnosis of liver disease. In the past, the AST test
was used to diagnose heart attack (myocardial infarction or MI) but more accurate blood tests have largely
replaced it for cardiac purposes.

Description
AST is determined by analysis of a blood sample,
usually from taken from a venipuncture site at the
bend of the elbow.
AST is found in the heart, liver, skeletal muscle,
kidney, pancreas, spleen, lung, red blood cells, and
brain tissue. When disease or injury affects these
tissues, the cells are destroyed and AST is released
into the bloodstream. The amount of AST is directly
GALE ENCYCLOPEDIA OF MEDICINE

Cirrhosis—Disease of the liver caused by chronic
damage to its cells.
Myocardial infarction—Commonly known as a
heart attack. Sudden death of part of the heart
muscle, characterized, in most cases, by severe,
unremitting chest pain.

related to the number of cells affected by the disease
or injury, but the level of elevation depends on the
length of time that the blood is tested after the
injury. Serum AST levels become elevated eight
hours after cell injury, peak at 24-36 hours, and
return to normal in three to seven days. If the
cellular injury is chronic (ongoing), AST levels will
remain elevated.
One of the most important uses for AST determination has formerly been in the diagnosis of a heart
attack, or MI. AST can assist in determining the
timing and extent of a recent MI, although it is less
specific than creatine phosphokinase (CPK), CKMB,
myglobin, troponins, and lactic dehydrogenase
(LDH). Assuming no further cardiac injury occurs,
the AST level rises within 6-10 hours after an acute
attack, peaks at 12-48 hours, and returns to normal
in three to four days. Myocardial injuries such as
angina (chest pain) or pericarditis (inflammation of
the pericardium, the membrane around the heart) do
not increase AST levels.
AST is also a valuable aid in the diagnosis of liver
disease. Although not specific for liver disease, it can
be used in combination with other enzymes to monitor
the course of various liver disorders. Chronic, silent
hepatitis (hepatitis C) is sometimes the cause of elevated AST. In alcoholic hepatitis, caused by excessive
alcohol ingestion, AST values are usually moderately
elevated; in acute viral hepatitis, AST levels can rise to
over 20 times normal. Acute extrahepatic (outside the
liver) obstruction (e.g. gallstone), produces AST levels
that can quickly rise to 10 times normal, and then
rapidly fall. In cases of cirrhosis, the AST level is
related to the amount of active inflammation of the
liver. Determination of AST also assists in early recognition of toxic hepatitis that results from exposure to
drugs toxic to the liver, like acetaminophen and
cholesterol lowering medications.
Other disorders or diseases in which the AST
determination can be valuable include acute
GALE ENCYCLOPEDIA OF MEDICINE

pancreatitis, muscle disease, trauma, severe burn, and
infectious mononucleosis.

Preparation
The physician may require discontinuation of any
drugs that might affect the test. These types include
such drugs as antihypertensives (for treatment of
high blood pressure), coumarin-type anticoagulants
(blood-thinning drugs), digitalis, erythromycin (an
antibiotic), oral contraceptives, and opiates, among
others. The patient may also need to cut back on
strenuous activities temporarily, because exercise can
also elevate AST for a day or two.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or
feeling lightheaded after venipuncture, or hematoma
(blood accumulating under the puncture site).

Normal results
Normal ranges for the AST are laboratoryspecific, but can range from 3-45 units/L (units per
liter).

Abnormal results
Striking elevations of AST (400-4000 units/L) are
found in almost all forms of acute hepatic necrosis,
such as viral hepatitis and carbon tetrachloride poisoning. In alcoholics, even moderate doses of the analgesic
acetaminophen have caused extreme elevations
(1, 960-29, 700 units/L). Moderate rises of AST are
seen in jaundice, cirrhosis, and metastatic carcinoma.
Approximately 80% of patients with infectious mononucleosis show elevations in the range of 100-600
units/L.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Asperger’s syndrome see Pervasive developmental disorders
Aspergilloma see Aspergillosis
419

Aspartate aminotransferase test

KEY TERMS

Aspergillosis

I Aspergillosis
Definition
Aspergillosis refers to several forms of disease
caused by a fungus in the genus Aspergillus.
Aspergillosis fungal infections can occur in the ear
canal, eyes, nose, sinus cavities, and lungs. In some
individuals, the infection can even invade bone and the
membranes that enclose the brain and spinal cord
(meningitis).

Description
Aspergillosis is primarily an infection of the lungs
caused by the inhalation of airborne spores of the
fungus Aspergillus. Spores are the small particles that
most fungi use to reproduce. Although virtually everyone is exposed to this fungus in their daily environment, it rarely causes disease. When Aspergillus does
cause disease, however, it usually occurs in those
individuals with weakened immune systems (immunocompromised) or who have a history of respiratory
ailments. Because it does not present distinctive symptoms, aspergillosis is generally thought to be underdiagnosed and underreported. Furthermore, many
patients with the more severe forms of aspergillosis
tend to have multiple, complex health problems, such
as AIDS or a blood disorder like leukemia, which can
further complicate diagnosis and treatment.
Once considered particularly rare, the incidence of
reported aspergillosis has risen somewhat with the
development of more sophisticated methods of diagnosis and advances made in other areas of medicine,
such as with the increased use of certain chemotherapeutic and corticosteroid drugs that are extremely
useful in treating various types of cancer but that
decrease the individual’s immune response, making
them more susceptible to other diseases like
aspergillosis.
Our advanced ability to perform tissue and organ
transplants has also increased the number of people
vulnerable to fungal infections. Transplant recipients,
particularly those receiving bone marrow or heart
transplants, are highly susceptible to Aspergillus,
which may be circulating in the hospital air.
Aspergillosis can be a serious, potentially deadly
threat for two primary reasons:


Aspergillosis usually occurs in those individuals who
are already ill or have weakened immune systems,
such as patients who have undergone chemotherapy
for cancer.

420

Aspergillus
Aspergillosis is an infection of the lungs caused by inhalation of airborne spores of the fungus Aspergillus. (Illustration
by Electronic Illustrators Group).

KEY TERMS
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Aspergilloma—A ball or mass made of Aspergillus
fungi that can form in the lungs of patients with
suppressed immune systems.
Bronchial lavage—A procedure that involves
repeatedly washing the inside of the bronchial
tubes of the lung.
Hemoptysis—Spitting up blood from the lungs or
sputum stained with blood.
Immunocompromised—A state in which the
immune system is suppressed or not functioning
properly.
Meningitis—Inflammation of the membranes covering the brain and spinal cord, called the meninges.
Nebulizer—A device that produces an extremely
fine mist that is readily inhalable.
Spores—The small, thick-walled reproductive
structures of fungi.
Sputum—Mucus and other matter coughed up
from the airways.

GALE ENCYCLOPEDIA OF MEDICINE

None of the currently available antifungal drugs are
reliably effective against Aspergillus.

Causes and symptoms
Airborne Aspergillus spores enter the body primarily through inhalation but can also lodge in the
ear or eye. Normally functioning immune systems are
generally able to cope without consequent development of aspergillosis.
It is important to make distinctions between the
various forms of aspergillosis, as the treatment and
prognosis varies considerably among types.
Aspergillosis as a diagnosis refers to three general
forms:


Allergic bronchopulmonary aspergillosis (ABPA) is
seen in patients with long-standing asthma, particularly in patients taking oral corticosteroids for a long
period of time. This is usually the least serious and
most treatable form.



Aspergilloma refers to the mass formed when fungal
spores settle into or colonize areas of the lung that
have been pitted and scarred as a result of tuberculosis or prior pneumonia. There are several available
treatments, although the success rate varies with each
treatment.



Invasive fungal infection refers to rare cases in which
the fungus spreads throughout the body via the
blood stream and invades other organ systems.
Once established, invasive fungal infections are
extremely difficult to cure and, as a result, the associated death rate is extremely high.

Diagnosis
Aspergillosis can be quite difficult to diagnose
because the symptoms, such as coughing and wheezing,
if present at all, are common to many respiratory
disorders. Furthermore, blood and sputum cultures
are not very helpful. The presence of Aspergillus is
so common, even in asthmatics, that a positive culture
alone is insufficient for a diagnosis. Other, potentially
more useful, screening tools include examining the
sample obtained after repeatedly washing the bronchial
tubes of the lung with water (bronchial lavage), but
examining a tissue sample (biopsy) is the most reliable
diagnostic tool. Researchers are currently attempting
to develop a practical, specific, and rapid blood test
that would confirm Aspergillus infection.
Signs of ABPA include a worsening of bronchial
asthma accompanied by a low-grade fever. Brown flecks
or clumps may be seen in the sputum. Pulmonary
GALE ENCYCLOPEDIA OF MEDICINE

function tests may show decreased blood flow, suggesting an obstruction within the lungs. Elevated blood levels
of an antibody produced in response to Aspergillus and
of certain immune system cells may indicate a specific
allergic-type immune system response.
A fungal mass (aspergilloma) in the lung usually
does not produce clear symptoms and is generally diagnosed when seen on chest x rays. However, 70% or
more of patients spit up blood from the lungs (hemoptysis) at least once, and this may become repetitive and
serious. Hemoptysis, then, is another indication that
the patient may be suffering from an aspergilloma.
In patients with lowered immune systems who are
at risk for developing invasive aspergillosis, the physician may use a combination of blood culture with
visual diagnostic techniques, such as computed tomography scans (CT) and radiography, to arrive at a
likely diagnosis.

Treatment
The treatment method selected depends on the
form of aspergillosis. ABPA can usually be treated
with many of the same drugs used to treat asthma,
such as systemic steroids. Long-term therapy may be
required, however, to prevent recurrence. Antifungal
agents are not recommended in the treatment of
ABPA. In cases of aspergilloma, it may become necessary to surgically remove or reduce the size of a fungal
mass, especially if the patient continues to spit up
blood. In aspergillosis cases affecting the nose and
nasal sinuses, surgery may also be required.
In non-ABPA cases, the use of antifungal drugs
may be indicated. In such cases, amphotericin B
(Fungizone) is the first-line therapy. The prescribed
dose will depend on the patient’s condition but usually
begins with a small test dose and then escalates. Less
than one-third of patients are likely to respond to
amphotericin B, and its side effects often limit its use.
For patients who do not respond to oral amphotericin
B, another option is a different formulation of the
same drug called liposomal amphotericin B.
For patients who fail to respond or who cannot
tolerate amphotericin B, another drug called itraconazole (Sporanox), given 400-600 mg daily, has also been
approved. Treatment generally lasts about 3 months.
Giving itraconazole can produce adverse reactions if
prescribed in combination with certain other drugs by
increasing the concentrations of both drugs in the
blood and creating a potentially life-threatening situation. Even antacids can significantly affect itraconazole levels. As a result, drug levels must be continually
421

Aspergillosis



Aspirin

monitored to ensure that absorption is occurring at
acceptable levels.
Two other methods of treatment are being
studied: direct instillation of an antifungal agent
into the lungs and administration of antifungals
using a nebulizer. Instilling or injecting amphotericin B or itraconazole directly into the lung cavity
or into the fungal ball (aspergilloma) itself has
been helpful in stopping episodes of hemoptysis,
but not in preventing future recurrences.
Furthermore, many patients with aspergillomas
are poor risks for surgery because their lung function is already compromised. As a result, instillation of a fungal agent should only be considered in
those who have significant hempotysis.
A popular method of treating some respiratory
disorders is to add a liquid drug to another carrier liquid
and aerosolize or produce a fine mist that can be inhaled
into the lungs through a device called a nebulizer.
However, this has not yet been shown to improve the
patient’s condition in cases of aspergillosis, possibly
because the drug is not reaching the aspergilloma.
At this point, preventative therapy for aspergillosis is not suggested for susceptible individuals, primarily because overuse of the drugs used to fight fungal
infections may lead to the development of drugresistant aspergillosis against which current antifungal
drugs are no longer effective.

Prognosis
The likelihood of recovery from aspergillosis
depends on any underlying medical conditions, the
patient’s general health, and the specific type of aspergillosis. If the problem is based on an allergic response,
as in ABPA, the patient will likely respond well to
systemic steroids.
Patients who require lung surgery, especially those
who have problems with coughing up blood, have a
mortality rate of about 7-14%, and complications or
recurrence may result in a higher overall death rate.
However, by treating aspergilloma with other, nonsurgical methods, that risk rises to 26%, making surgery a better option in some cases.
Unfortunately, the prognosis for the most serious
form, invasive aspergillosis, is quite poor, largely
because these patients have little resilience due to
their underlying disorders. Death rates have ranged
from about 50% in some studies to as high as 95% for
bone-marrow recipients and patients with AIDS. The
course of the illness can be rapid, resulting in death
within a few months of diagnosis.
422

Prevention
Fungal infection by Aspergillus presents a major
challenge, particularly in the patient with a suppressed
immune system (immunocompromised). Hospitals
and government health agencies continually seek
ways to minimize exposure for hospitalized patients.
Practical suggestions are minimal but include moving
leaf piles away from the house. Unfortunately, overall
avoidance of this fungus is all but impossible because
it is present in the environment virtually everywhere.
Research efforts are being directed at enhancing
patients’ resistance to Aspergillus rather than trying
to eliminate exposure to the fungus. Given the growing number of people with immune disorders or whose
immune systems have been suppressed in the course of
treating another disease, research and clinical trials
for new antifungal agents will be increasingly important in the future.
Resources
ORGANIZATIONS

American College of Allergy, Asthma, and Immunology.
85 West Algonquin Road, Suite 550, Arlington Heights,
IL 60005. <http://allergy.mcg.edu>.
OTHER

‘‘Lung, Allergic and Immune Diseases: Mold Allergy:
Prevention Techniques.’’ National Jewish Medical and
Research.<http://nationaljewish.org/main.html>.
Office of Rare Diseases (ORD) at National Institutes
of Health, Bldg. 31,1BO3, Bethesda, MD 208922082. (301) 402-4336<http://
rarediseases.info.nih.gov/ord>.

Jill S. Lasker

I Aspirin
Definition
Aspirin is a medicine that relieves pain and reduces
fever.

Purpose
Aspirin is used to relieve many kinds of minor
aches and pains–headaches, toothaches, muscle pain,
menstrual cramps, the joint pain from arthritis, and
aches associated with colds and flu. Some people take
aspirin daily to reduce the risk of stroke, heart attack,
or other heart problems.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Aspirin–also known as acetylsalicylic acid–is sold
over the counter and comes in many forms, from the
familiar white tablets to chewing gum and rectal suppositories. Coated, chewable, buffered, and extended
release forms are available. Many other over-thecounter medicine contain aspirin. Alka-Seltzer
Original Effervescent Antacid Pain Reliever, for
example, contains aspirin for pain relief and sodium
bicarbonate to relieve acid indigestion, heartburn, and
sour stomach.

Diuretic—Medicine that increases the amount of
urine produced and relieves excess fluid buildup in
body tissues. Diuretics may be used in treating high
blood pressure, lung disease, premenstrual syndrome, and other conditions.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
NSAIDs—Nonsteroidal anti-inflammatory drugs.
Drugs such as ketoprofen and ibuprofen which
relieve pain and reduce inflammation.

Aspirin belongs to a group of drugs called salicylates. Other members of this group include sodium
salicylate, choline salicylate, and magnesium salicylate. These drugs are more expensive and no more
effective than aspirin. However, they are a little easier
on the stomach. Aspirin is quickly absorbed into the
bloodstream and provides quick and relatively longlasting pain relief. Aspirin also reduces inflammation.
Researchers believe these effects come about because
aspirin blocks the production of pain-producing chemicals called prostaglandins.

Polyp—A lump of tissue protruding from the lining
of an organ, such as the nose, bladder, or intestine.
Polyps can sometimes block the passages in which
they are found.
Prostaglandin—A hormonelike chemical produced
in the body. Prostaglandins have a wide variety of
effects, and may be responsible for the production
of some types of pain and inflammation.
Reye’s syndrome—A life-threatening disease that
affects the liver and the brain and sometimes occurs
after a viral infection, such as flu or chickenpox.
Children or teenagers who are given aspirin for flu
or chickenpox are at increased risk of developing
Reye’s syndrome.
Rhinitis—Inflammation of the membranes inside
the nose.

In addition to relieving pain and reducing inflammation, aspirin also lowers fever by acting on the part
of the brain that regulates temperature. The brain then
signals the blood vessels to widen, which allows heat to
leave the body more quickly.

Recommended dosage

Salicylates—A group of drugs that includes aspirin
and related compounds. Salicylates are used to
relieve pain, reduce inflammation, and lower fever.

Adults
TO RELIEVE PAIN OR REDUCE FEVER. One to two
tablets every three to four hours, up to six times per day.
TO REDUCE THE RISK OF STROKE. One tablet four
times a day or two tablets twice a day.
TO REDUCE THE RISK OF HEART ATTACK. Check with

a physician for the proper dose and number of times
per week aspirin should, if at all, be taken.
Children
Check with a physician.

Precautions
Aspirin–even children’s aspirin–should never be
given to children or teenagers with flu-like symptoms
or chickenpox. Aspirin can cause Reye’s syndrome, a
life-threatening condition that affects the nervous system and liver. As many as 30% of children and teenagers who develop Reye’s syndrome die. Those who
survive may have permanent brain damage.
GALE ENCYCLOPEDIA OF MEDICINE

Aspirin

Description

Check with a physician before giving aspirin to a
child under 12 years for arthritis, rheumatism, or any
condition that requires long-term use of the drug.
No one should take aspirin for more than 10 days
in a row unless told to do so by a physician. Anyone
with fever should not take aspirin for more than 3 days
without a physician’s consent. Do not to take more
than the recommended daily dosage.
People in the following categories should not use
aspirin without first checking with their physician:


Pregnant women. Aspirin can cause bleeding problems in both the mother and the developing fetus.
Aspirin can also cause the infant’s weight to be too
low at birth.



Women who are breastfeeding. Aspirin can pass into
breast milk and may affect the baby.
423

Asthma



People with a history of bleeding problems.



People who are taking blood-thinning drugs, such as
warfarin (Coumadin).



People with a history of ulcers.



People with a history of asthma, nasal polyps, or
both. These people are more likely to be allergic to
aspirin.



People who are allergic to fenoprofen, ibuprofen,
indomethacin, ketoprofen, meclofenamate sodium,
naproxen, sulindac, tolmetin, or the orange foodcoloring tartrazine. They may also be allergic to
aspirin.



People with AIDS or AIDS-related complex who are
taking AZT (zidovudine). Aspirin can increase the
risk of bleeding in these patients.



People taking certain other drugs (discussed in
Interactions).



People with liver damage or severe kidney failure.

Aspirin should not be taken before surgery, as it
can increase the risk of excessive bleeding. Anyone
who is scheduled for surgery should check with his or
her surgeon to find out how long before surgery to
avoid taking aspirin.
Aspirin can cause stomach irritation. To reduce
the likelihood of that problem, take aspirin with food
or milk or drink a full 8-oz glass of water with it.
Taking coated or buffered aspirin can also help. Be
aware that drinking alcohol can make the stomach
irritation worse.

blood in stools. Less common side effects are rashes,
hives, fever, vision problems, liver damage, thirst, stomach ulcers, and bleeding. People who are allergic to
aspirin or those who have asthma, rhinitis, or polyps in
the nose may have trouble breathing after taking
aspirin.

Interactions
Aspirin may increase, decrease, or change the
effects of many drugs. Aspirin can make drugs such
as methotrexate (Rheumatrex) and valproic acid
(Depakote, Depakene) more toxic. If taken with
blood-thinning drugs, such as warfarin (Coumadin)
and dicumarol, aspirin can increase the risk of
excessive bleeding. Aspirin counteracts the effects
of other drugs, such as angiotensin-converting
enzyme (ACE) inhibitors and beta blockers, which
lower blood pressure, and medicines used to treat
gout (probenecid and sulfinpyrazone). Blood pressure may drop unexpectedly and cause fainting or
dizziness if aspirin is taken along with nitroglycerin
tablets. Aspirin may also interact with diuretics,
diabetes medicines, other nonsteroidal anti-inflammatory drugs (NSAIDs), seizure medications, and
steroids. Anyone who is taking these drugs should
ask his or her physician whether they can safely
take aspirin.
Resources
PERIODICALS

‘‘What’s the Best Pain Reliever? Depends on Your Pain.’’
Consumer Reports May 1996: 62.

Stop taking aspirin immediately and call a physician if any of these symptoms develop:

Nancy Ross-Flanigan



ringing or buzzing in the ears



hearing loss

AST see Aspartate aminotransferase test



dizziness

Astemizole see Antihistamines



stomach pain that does not go away

Do not take aspirin that has a vinegary smell.
That is a sign that the aspirin is too old and ineffective.
Flush such aspirin down the toilet.
Because aspirin can increase the risk of excessive bleeding, do not take aspirin daily over long
periods–to reduce the risk of stroke or heart
attack, for example–unless advised to do so by a
physician.

Side effects
The most common side effects include stomachache, heartburn, loss of appetite, and small amounts of
424

I Asthma
Definition
Asthma is a chronic (long-lasting) inflammatory
disease of the airways. In those susceptible to asthma,
this inflammation causes the airways to narrow periodically. This, in turn, produces wheezing and breathlessness, sometimes to the point where the patient
gasps for air. Obstruction to air flow either stops
spontaneously or responds to a wide range of treatments, but continuing inflammation makes the
GALE ENCYCLOPEDIA OF MEDICINE

Asthma

In normal bronchioles the airway
is open and unobstructed.

During an attack, the bronchioles of an
asthma sufferer are constricted by bands
of muscle around them. They may be
further obstructed by increased mucus
production and tissue inflammation.

A comparison of normal bronchioles and those of an asthma sufferer. (Illustration by Hans & Cassady.)

airways hyper-responsive to stimuli such as cold air,
exercise, dust mites, pollutants in the air, and even
stress and anxiety.

Description
Between 17 million and 26 million Americans
have asthma, and the number seems to be increasing.
In about 1992, the number with asthma was about
10 million, and had risen 42% from 1982, just 10 years
prior. Not only is asthma becoming more frequent,
but it also is a more severe disease than before, despite
modern drug treatments. Asthma accounts for almost
500,000 hospitalizations, two million emergency
department visits, and 5,000 deaths in the United
States each year.
GALE ENCYCLOPEDIA OF MEDICINE

The changes that take place in the lungs of asthmatic persons makes the airways (the ‘‘breathing
tubes,’’ or bronchi and the smaller bronchioles) hyperreactive to many different types of stimuli that don’t
affect healthy lungs. In an asthma attack, the muscle
tissue in the walls of bronchi go into spasm, and the
cells lining the airways swell and secrete mucus into the
air spaces. Both these actions cause the bronchi to
become narrowed (bronchoconstriction). As a result,
an asthmatic person has to make a much greater effort
to breathe in air and to expel it.
Cells in the bronchial walls, called mast cells,
release certain substances that cause the bronchial
muscle to contract and stimulate mucus formation.
These substances, which include histamine and a
425

Asthma

Adult-onset asthma

KEY TERMS
Allergen—A foreign substance, such as mites in
house dust or animal dander which, when inhaled,
causes the airways to narrow and produces symptoms of asthma.
Atopy—A state that makes persons more likely to
develop allergic reactions of any type, including
the inflammation and airway narrowing typical of
asthma.
Hypersensitivity—The state where even a tiny
amount of allergen can cause the airways to constrict and bring on an asthmatic attack.
Spirometry—A test using an instrument called a
spirometer that shows how difficult it is for an asthmatic patient to breathe. Used to determine the
severity of asthma and to see how well it is responding to treatment.

group of chemicals called leukotrienes, also bring
white blood cells into the area, which is a key part of
the inflammatory response. Many patients with
asthma are prone to react to such ‘‘foreign’’ substances as pollen, house dust mites, or animal dander;
these are called allergens. On the other hand, asthma
affects many patients who are not allergic in this way.
Asthma usually begins in childhood or adolescence, but it also may first appear during adult years.
While the symptoms may be similar, certain important
aspects of asthma are different in children and adults.
Child-onset asthma
Nearly one-third on the 17 to 26 million
Americans with asthma are children. When asthma
begins in childhood, it often does so in a child who is
likely, for genetic reasons, to become sensitized to
common allergens in the environment (atopic person).
When these children are exposed to house-dust mites,
animal proteins, fungi, or other potential allergens,
they produce a type of antibody that is intended to
engulf and destroy the foreign materials. This has the
effect of making the airway cells sensitive to particular
materials. Further exposure can lead rapidly to an
asthmatic response. This condition of atopy is present
in at least one-third and as many as one-half of the
general population. When an infant or young child
wheezes during viral infections, the presence of allergy
(in the child or a close relative) is a clue that asthma
may well continue throughout childhood.
426

Allergenic materials may also play a role when
adults become asthmatic. Asthma can actually start
at any age and in a wide variety of situations. Many
adults who are not allergic have conditions such as
sinusitis or nasal polyps, or they may be sensitive to
aspirin and related drugs. Another major source of
adult asthma is exposure at work to animal products,
certain forms of plastic, wood dust, or metals.

Causes and symptoms
In most cases, asthma is caused by inhaling an
allergen that sets off the chain of biochemical and
tissue changes leading to airway inflammation,
bronchoconstriction, and wheezing. Because avoiding
(or at least minimizing) exposure is the most effective
way of treating asthma, it is vital to identify which
allergen or irritant is causing symptoms in a particular
patient. Once asthma is present, symptoms can be set
off or made worse if the patient also has rhinitis
(inflammation of the lining of the nose) or sinusitis.
When, for some reason, stomach acid passes back up
the esophagus (acid reflux), this can also make asthma
worse. A viral infection of the respiratory tract can
also inflame an asthmatic reaction. Aspirin and a type
of drug called beta-blockers, often used to treat high
blood pressure, can also worsen the symptoms of
asthma.
The most important inhaled allergens giving rise
to attacks of asthma are:


animal dander



mites in house dust



fungi (molds) that grow indoors



cockroach allergens



pollen



occupational exposure to chemicals, fumes, or particles of industrial materials in the air

Inhaling tobacco smoke, either by smoking or
being near people who are smoking, can irritate the
airways and trigger an asthmatic attack. Air pollutants can have a similar effect. In addition, there are
three important factors that regularly produce attacks
in certain asthmatic patients, and they may sometimes
be the sole cause of symptoms. They are:


inhaling cold air (cold-induced asthma)



exercise-induced asthma (in certain children, asthma
is caused simply by exercising)



stress or a high level of anxiety
GALE ENCYCLOPEDIA OF MEDICINE

Being short of breath may cause a patient to
become very anxious, sit upright, lean forward, and
use the muscles of the neck and chest wall to help
breathe. The patient may be able to say only a few
words at a time before stopping to take a breath.
Confusion and a bluish tint to the skin are clues
that the oxygen supply is much too low, and that
emergency treatment is needed. In a severe attack
that lasts for some time, some of the air sacs in the
lung may rupture so that air collects within the
chest. This makes it even harder to breathe in
enough air.

Diagnosis
Apart from listening to the patient’s chest, the
examiner should look for maximum chest expansion
while taking in air. Hunched shoulders and contracting neck muscles are other signs of narrowed airways.
Nasal polyps or increased amounts of nasal secretions
are often noted in asthmatic patients. Skin changes,
like atopic dermatitis or eczema, are a tipoff that the
patient has allergic problems.
Inquiring about a family history of asthma or
allergies can be a valuable indicator of asthma. The
diagnosis may be strongly suggested when typical
symptoms and signs are present. A test called spirometry measures how rapidly air is exhaled and how
much is retained in the lungs. Repeating the test after
the patient inhales a drug that widens the air passages
(a bronchodilator) will show whether the airway narrowing is reversible, which is a very typical finding in
asthma. Often patients use a related instrument, called
GALE ENCYCLOPEDIA OF MEDICINE

a peak flow meter, to keep track of asthma severity
when at home.
Often, it is difficult to determine what is triggering
asthma attacks. Allergy skin testing may be used,
although an allergic skin response does not always
mean that the allergen being tested is causing the
asthma. Also, the body’s immune system produces
antibody to fight off the allergen, and the amount of
antibody can be measured by a blood test. This will
show how sensitive the patient is to a particular allergen. If the diagnosis is still in doubt, the patient can
inhale a suspect allergen while using a spirometer to
detect airway narrowing. Spirometry can also be
repeated after a bout of exercise if exercise-induced
asthma is a possibility. A chest x ray will help rule
out other disorders.

Treatment
Patients should be periodically examined and
have their lung function measured by spirometry to
make sure that treatment goals are being met. These
goals are to prevent troublesome symptoms, to maintain lung function as close to normal as possible, and
to allow patients to pursue their normal activities
including those requiring exertion. The best drug therapy is that which controls asthmatic symptoms while
causing few or no side-effects.
Drugs
METHYLXANTHINES. The chief methylxanthine
drug is theophylline. It may exert some anti-inflammatory effect, and is especially helpful in controlling
nighttime symptoms of asthma. When, for some reason, a patient cannot use an inhaler to maintain longterm control, sustained-release theophylline is a good
alternative. The blood levels of the drug must be measured periodically, as too high a dose can cause an
abnormal heart rhythm or convulsions.
BETA-RECEPTOR AGONISTS. These drugs, which
are bronchodilators, are the best choice for relieving
sudden attacks of asthma and for preventing attacks
from being triggered by exercise. Some agonists, such
as albuterol, act mainly in lung cells and have little
effect on other organs, such as the heart. These
drugs generally start acting within minutes, but
their effects last only four to six hours. Longer-acting
brochodilators have been developed. They may last
up to 12 hours. Bronchodilators may be taken in pill
or liquid form, but normally are used as inhalers,
which go directly to the lungs and result in fewer
side effects.

427

Asthma

Wheezing is often obvious, but mild asthmatic
attacks may be confirmed when the physician listens
to the patient’s chest with a stethoscope. Besides
wheezing and being short of breath, the patient
may cough and may report a feeling of ‘‘tightness’’
in the chest. Children may have itching on their
back or neck at the start of an attack. Wheezing is
often loudest when the patient breathes out, in an
attempt to expel used air through the narrowed
airways. Some asthmatics are free of symptoms
most of the time but may occasionally be short of
breath for a brief time. Others spend much of their
days (and nights) coughing and wheezing, until
properly treated. Crying or even laughing may
bring on an attack. Severe episodes are often seen
when the patient gets a viral respiratory tract infection or is exposed to a heavy load of an allergen or
irritant. Asthmatic attacks may last only a few minutes or can go on for hours or even days (a condition called status asthmaticus).

Asthma

STEROIDS. These drugs, which resemble natural
body hormones, block inflammation and are extremely effective in relieving symptoms of asthma.
When steroids are taken by inhalation for a long
period, asthma attacks become less frequent as the
airways become less sensitive to allergens. This is
the strongest medicine for asthma, and can control
even severe cases over the long term and maintain
good lung function. Steroids can cause numerous
side-effects, however, including bleeding from the
stomach, loss of calcium from bones, cataracts in
the eye, and a diabetes-like state. Patients using
steroids for lengthy periods may also have problems
with wound healing, may gain weight, and may
suffer mental problems. In children, growth may
be slowed. Besides being inhaled, steroids may be
taken by mouth or injected, to rapidly control
severe asthma.
LEUKOTRIENE MODIFIERS. Leukotriene modifiers

(montelukast and zafirlukast) are a new type of
drug that can be used in place of steroids, for
older children or adults who have a mild degree of
asthma that persists. They work by counteracting
leukotrienes, which are substances released by white
blood cells in the lung that cause the air passages to
constrict and promote mucus secretion. Leukotriene
modifiers also fight off some forms of rhinitis, an
added bonus for people with asthma. However, they
are not proven effective in fighting seasonal
allergies.
OTHER DRUGS. Cromolyn and nedocromil are
anti-inflammatory drugs that are often used as
initial treatment to prevent asthmatic attacks over
the long term in children. They can also prevent
attacks when given before exercise or when exposure to an allergen cannot be avoided. These are
safe drugs but are expensive, and must be taken
regularly even if there are no symptoms. Anti-cholinergic drugs, such as atropine, are useful in controlling severe attacks when added to an inhaled
beta-receptor agonist. They help widen the airways
and suppress mucus production.

If a patient’s asthma is caused by an allergen that
cannot be avoided and it has been difficult to control
symptoms by drugs, immunotherapy may be worth
trying. Typically, increasing amounts of the allergen
are injected over a period of three to five years, so that
the body can build up an effective immune response.
There is a risk that this treatment may itself cause the
airways to become narrowed and bring on an asthmatic attack. Not all experts are enthusiastic about
immunotherapy, although some studies have shown
that it reduces asthmatic symptoms caused by
428

exposure to house-dust mites, ragweed pollen, and
cat dander.
Managing asthmatic attacks
A severe asthma attack should be treated as
quickly as possible. It is most important for a patient
suffering an acute attack to be given extra oxygen.
Rarely, it may be necessary to use a mechanical ventilator to help the patient breathe. A beta-receptor agonist is inhaled repeatedly or continuously. If the
patient does not respond promptly and completely, a
steroid is given. A course of steroid therapy, given
after the attack is over, will make a recurrence less
likely.
Maintaining control
Long-term asthma treatment is based on inhaling
a beta-receptor agonist using a special inhaler that
meters the dose. Patients must be instructed in proper
use of an inhaler to be sure that it will deliver the right
amount of drug. Once asthma has been controlled for
several weeks or months, it is worth trying to cut down
on drug treatment, but this must be done gradually.
The last drug added should be the first to be reduced.
Patients should be seen every one to six months,
depending on the frequency of attacks.
Starting treatment at home, rather than in a hospital, makes for minimal delay and helps the patient to
gain a sense of control over the disease. All patients
should be taught how to monitor their symptoms so
that they will know when an attack is starting, and
those with moderate or severe asthma should know
how to use a flow meter. They should also have a
written ‘‘action plan’’ to follow if symptoms suddenly
become worse, including how to adjust their medication and when to seek medical help. A 2004 report said
that a review of medical studies revealed that patients
with self-management written action plans had fewer
hospitalizations, fewer emergency department visits,
and improved lung function. They also had a 70%
lower mortality rate. If more intense treatment is necessary, it should be continued for several days. Over-thecounter ‘‘remedies’’ should be avoided. When deciding
whether a patient should be hospitalized, the past history of acute attacks, severity of symptoms, current
medication, and whether good support is available at
home all must be taken into account.
Referral to an asthma specialist should be considered if:


there has been a life-threatening asthma attack or
severe, persistent asthma
GALE ENCYCLOPEDIA OF MEDICINE

treatment for three to six months has not met its
goals



some other condition, such as nasal polyps or
chronic lung disease, is complicating asthma



special tests, such as allergy skin testing or an allergen challenge, are needed



intensive steroid therapy has been necessary
Special populations

respiratory failure, for which they must receive
intensive treatment.

Prevention
Minimizing exposure to allergens
There are a number of ways to cut down exposure
to the common allergens and irritants that provoke
asthmatic attacks, or to avoid them altogether:


If the patient is sensitive to a family pet, removing the
animal or at least keeping it out of the bedroom (with
the bedroom door closed), as well as keeping the pet
away from carpets and upholstered furniture and
Removing hair and feathers.



To reduce exposure to house dust mites, removing
wall-to-wall carpeting, keeping humidity down, and
using special pillows and mattress covers. Cutting
down on stuffed toys, and washing them each week
in hot water.



If cockroach allergen is causing asthma attacks, killing the roaches (using poison, traps, or boric acid
rather than chemicals). Taking care not to leave food
or garbage exposed.



Keeping indoor air clean by vacuuming carpets
once or twice a week (with the patient absent),
avoiding using humidifiers. Using air conditioning
during warm weather (so that the windows can be
closed).



Avoiding exposure to tobacco smoke.



Not exercising outside when air pollution levels are
high.



When asthma is related to exposure at work, taking
all precautions, including wearing a mask and, if
necessary, arranging to work in a safer area.

INFANTS AND YOUNG CHILDREN. It is especially

important to closely watch the course of asthma in
young patients. Treatment is cut down when possible
and if there is no clear improvement, some other treatment should be tried. If a viral infection leads to severe
asthmatic symptoms, steroids may help. The health
care provider should write out an asthma treatment
plan for the child’s school. Asthmatic children often
need medication at school to control acute symptoms
or to prevent exercise-induced attacks. Proper management will usually allow a child to take part in play
activities. Only as a last resort should activities be
limited.
THE ELDERLY. Older persons often have other
types of obstructive lung disease, such as chronic
bronchitis or emphysema. This makes it important
to know to what extent the symptoms are caused
by asthma. Giving steroids for two to three weeks
can help determine this. Side-effects from betareceptor agonist drugs (including a speeding heart
and tremor) may be more common in older
patients. These patients may benefit from receiving
an anti-cholinergic drug, along with the beta-receptor agonist. If theophylline is given, the dose
should be limited, as older patients are less able
to clear this drug from their blood. Steroids should
be avoided, as they often make elderly patients
confused and agitated. Steroids may also further
weaken the bones.

Prognosis
Most patients with asthma respond well when
the best drug or combination of drugs is found, and
they are able to lead relatively normal lives. More
than one-half of affected children stop having
attacks by the time they reach 21 years of age.
Many others have less frequent and less severe
attacks as they grow older. Urgent measures to
control asthma attacks and ongoing treatment to
prevent attacks are equally important. A small minority of patients will have progressively more trouble breathing and run a risk of going into
GALE ENCYCLOPEDIA OF MEDICINE

More than 80% of people with asthma have
rhinitis and recent research emphasizes that treating
rhinitis helps benefit ashtma. Prescription nasal steroids and other methods to control rhinitis (in addition to avoiding known allergens) can help prevent
asthma attacks. It is also important for patients to
keep open communication with physicians to ensure
that the correcnt amount of medication is being
taken.
Resources
PERIODICALS

‘‘Many People With Asthma ArenÆt Taking the Right
Amount of Medication.’’ Obesity, Fitness & Wellness
Week (September 25, 2004): 87.
429

Asthma



Astigmatism

Mintz, Matthew. ‘‘Asthma Update: Part 1. Diagnosis,
Monitoring, and Prevention of Disease Progression.’’
American Family Physician September 1, 2004: 893.
Solomon, Gina, Elizabeth H. Humphreys, and Mark D.
Miller. ‘‘Asthma and the Environment: Connecting the
Dots: What Role do Environmental Exposures Play in
the Rising Prevalence and Severity of Asthma?’’
Contemporary Peditatrics August 2004: 73–81.
‘‘WhatÆs New in: Asthma and Allergic Rhinitis.’’ Pulse
September 20, 2004: 50.

Retina
Cornea

Light
Lens

ORGANIZATIONS

Asthma and Allergy Foundation of America. 1233 20th
Street, NW, Suite 402, Washington, DC 20036. (800)
727-8462. <http://www.aafa.org>.
Mothers of Asthmatics, Inc. 3554 Chain Bridge Road, Suite
200, Fairfax, VA 22030. (800) 878-4403.
National Asthma Education Program. 4733 Bethesda Ave.,
Suite 350, Bethesda, MD 20814. (301) 495-4484.
National Jewish Medical and Research Center. 1400
Jackson St., Denver, CO 80206. (800) 222-LUNG.

David A. Cramer, MD
Teresa G. Odle

I Astigmatism

Horizontal line out of focus

Light

Astigmatism corrected by lens

Definition
Astigmatism is the result of an inability of the
cornea to properly focus an image onto the retina.
The result is a blurred image.

Astigmatism can be treated by the use of cylindrical lenses.
The lenses are shaped to counteract the shape of the sections of the cornea that are causing the difficulty. (Illustration
by Electronic Illustrators Group.)

Description
The cornea is the outermost part of the eye. It is a
transparent layer that covers the colored part of the eye
(iris), pupil, and lens. The cornea bends light and helps
to focus it onto the retina where specialized cells (photo
receptors) detect light and transmit nerve impulses via
the optic nerve to the brain where the image is formed.
The cornea is dome shaped. Any incorrect shaping of
the cornea results in an incorrect focusing of the light
that passes through that part of the cornea. The bending
of light is called refraction and focusing problems with
the cornea are called diseases of refraction or refractive
disorders. Astigmatism is an image distortion that
results from an improperly shaped cornea. Usually the
cornea is spherically shaped, like a baseball. However, in
astigmatism the cornea is elliptically shaped, more like a
football. There is a long meridian and a short meridian.
These two meridians generally have a constant curvature and are generally perpendicular to each other
430

(regular astigmatism). Irregular astigmatism may have
more than two meridians of focus and they may not be
908 apart. A point of light, therefore, going through an
astigmatic cornea will have two points of focus, instead
of one nice sharp image on the retina. This will cause the
person to have blurry vision. What the blur looks like
will depend upon the amount and the direction of the
astigmatism. A person with nearsightedness (myopia) or
farsightedness (hyperopia) may see a dot as a blurred
circle. A person with astigmatism may see the same dot
as a blurred oval or frankfurter-shaped blur.
Some cases of astigmatism are caused by problems
in the lens of the eye. Minor variations in the curvature
of the lens can produce minor degrees of astigmatism
(lenticular astigmatism). In these patients, the cornea is
usually normal in shape. Infants, as a group, have the
least amount of astigmatism. Astigmatism may increase
during childhood, as the eye is developing.
GALE ENCYCLOPEDIA OF MEDICINE

Meridian—A section of a sphere. For example,
longitude or latitude on the globe. Or, on a clock, a
section going through 12:00-6:00 or 3:00-9:00, etc.
Refraction—The turning or bending of light waves
as the light passes from one medium or layer to
another. In the eye it means the ability of the eye
to bend light so that an image is focused onto the
retina.

Causes and symptoms
The main symptom of astigmatism is blurring.
People can also experience headaches and eyestrain.
Parents can notice that a child may have astigmatism when the child can see some part of a pattern
or picture more clearly than others. For example,
lines going across may seem clearer than lines going
up and down.
Regular astigmatism can be caused by the weight
of the upper eyelid resting on the eyeball creating
distortion, surgical incisions in the cornea, trauma or
scarring to the cornea, the presence of tumors in the
eyelid, or a developmental factor. Irregular astigmatism can be caused by scarring or keratoconus.
Keratoconus is a condition in which the cornea thins
and becomes cone shaped. It usually occurs around
puberty and is more common in women. Although the
causes of keratoconus are unknown, it may be hereditary or a result of chronic eye rubbing, as in people
with allergies. The center of the cone may not be in line
with the center of the cornea. Diabetes can play a role
in the development of astigmatism. High blood sugar
levels can cause shape changes in the lens of the eye.
This process usually occurs slowly and, often, is only
noticed when the diabetic has started treatment to
control their blood sugar. The return to a more normal
blood sugar allows the lens to return to normal and
this change is sometimes noticed by the patient as
farsightedness. Because of this, diabetics should wait
until their blood sugar is under control for at least one
month to allow vision to stabilize before being measured for eyeglasses.

Diagnosis
Patients seek treatment because of blurred vision.
A variety of tests can be used to detect astigmatism
during the eye exam. The patient may be asked to
GALE ENCYCLOPEDIA OF MEDICINE

describe the astigmatic dial, a series of lines that radiate outward from a center. People with astigmatism
will see some of the lines more clearly than others.
One diagnostic instrument used is the keratometer.
This measures the curvature of the central cornea.
It measures the amount and direction of the curvature.
A corneal topographer can measure a larger area of
the cornea. It can measure the central area and
mid-periphery of the cornea. A keratoscope projects
a series of concentric light rings onto the cornea.
Misshapen areas of the cornea are revealed by noting
areas of the light pattern that do not appear concentric on the cornea. Because these instruments are
measuring the cornea, it is also important to have a
refraction in case the lens is also contributing to the
astigmatism. The refraction measures the optics or
visual status of the eye and the result is the eyeglass
prescription. The refraction is when the patient is looking at an eye chart and the doctor is putting different
lenses in front of the patient’s eyes and asks which one
looks better.

Treatment
Astigmatism can be treated by the use of cylindrical lenses. They can be in eyeglasses or contact lenses.
The unit of measure describing the power of the lens
system or lens is called the diopter (D). The lenses are
shaped to counteract the shape of the sections of
cornea that are causing the difficulty. Because the
correction is in one direction, it is written in terms of
the axis the correction is in. On a prescription, for
example, it may say -1.00  1808. Cylinders correct
astigmatism, minus spheres correct myopia, and plus
spheres correct hyperopia.
There is some debate as to whether people with
very small amounts of astigmatism should be treated.
Generally, if visual acuity is good and the patient
experiences no overt symptoms, treatment is not
necessary. When treating larger amounts of astigmatism, or astigmatism for the first time, the doctor may
not totally correct the astigmatism. The cylindrical
correction in the eyeglasses may make the floor appear
to tilt, thus making it difficult for the patient at first.
Generally, the doctor will place lenses in a trial frame
to allow the patient to try the prescription at the exam.
It may take a week or so to get used to the glasses,
however, if the patient is having a problem they should
contact their doctor, who might want to recheck the
prescription.
Contact lenses that are used to correct astigmatism are called toric lenses. When a person blinks, the
contact lens rotates. In toric lenses, it is important for
431

Astigmatism

KEY TERMS

Aston-Patterning

the lens to return to the same position each time.
Lenses have thin zones, or cut-off areas (truncated),
or have other ways to rotate and return to the correct
position. Soft toric lenses are available in a variety of
prescriptions, materials, and even in tints. Patients
should ask their doctors about the possibility of toric
lenses.

JUDITH ASTON
Judith Aston was born in Long Beach, California. She
graduated from University of California at Los Angeles
with a B.A. and a M.F.A. in dance. Her interest in movement arose from working as a dancer. In 1963 Aston
established her first movement education program for
dancers, actors, and athletes at Long Beach City College.

In 1997, the Food and Drug Administration
(FDA) approved laser treatment of astigmatism.
Patients considering this should make sure the surgeon
has a lot of experience in the procedure and discuss the
possible side effects or risks with the doctor. In the
case of keratoconus, a corneal transplant is performed
if the astigmatism can not be corrected with hard
contact lenses.

Five years later, while recovering from injuries sustained during two consecutive automobile accidents,
Aston met Ida Rolf, the developer of Rolfing. Aston
began working for Rolf, teaching a movement education
program called Rolf-Aston Structural Patterning that
emphasized using the body with minimum effort and
maximum precision.
In time, Rolf and Aston’s views on movement diverged,
and the partnership was dissolved in 1977. Aston formed her
own company called the Aston Paradigm Corporation in
Lake Tahoe, California. This company provides training
and certification for Aston practitioners. She also began
exploring how environmental conditions affect body
movement, foreshadowing the ergonomic movement in
the workplace that developed in the 1990s. Over time,
Aston has expanded her movement work to include a
fitness program for older adults. Today, Judith Aston
serves as director of Aston Paradigm Corporation.

Prognosis
Astigmatism is a condition that may be present at
birth. It may also be acquired if something is distorting
the cornea. Vision can generally be corrected with
eyeglasses or contact lenses. The major risks of surgery
(aside from the surgical risks) are over and under
correction of the astigmatism. There is no cure for
over correction. Under correction can be solved by
repeating the operation.
Resources
BOOKS

Berkow, Robert, editor. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

simple movements of everyday life to dissipate tension
in the body. This is done through massage, alteration
of the environment, and fitness training.

John T. Lohr, PhD

I Aston-Patterning
Definition
Aston-Patterning is an integrated system of movement education, bodywork, ergonomic adjustments,
and fitness training that recognizes the relationship
between the body and mind for well being. It helps
people who seek a remedy from acute or chronic pain
by teaching them to improve postural and movement
patterns.

Purpose
Aston-Patterning assists people in finding more
efficient and less stressful ways of performing the
432

Description
Seeking to solve movement problems, AstonPatterning helps make the most of their own unique
body types rather than trying to force them to conform
to an ideal. Unlike Rolfing, it doesn’t strive for linear
symmetry. Rather it works with asymmetry in the
human body to develop patterns of alignment and
movement that feel right to the individual. Aston
also introduced the idea of working in a three-dimensional spinal pattern. Aston-Patterning sessions have
four general components. They are:


A personal history that helps the practitioner assess
the client’s needs.



Pre-testing, in which the practitioner and the client
explore patterns of movement and potential for
improvement.



Movement education and bodywork, including massage, myofacial release, and arthrokinetics, to help
release tension and make new movement patterns easier.
GALE ENCYCLOPEDIA OF MEDICINE

Rolfing—Developed by Dr. Ida Rolf (1896–1979),
rolfing is a systematic approach to relieving stress
patterns and dysfunctions in the body’s structure
through the manipulation of the highly pliant myofacial (connective) tissue. It assists the body in reorganizing its major segments into vertical alignment.



limitations of Aston-Patterning. Its claims have been
neither proven nor disproved, although anecdotally
many clients report relief from pain and tension and
also improved body movement.
Resources
ORGANIZATIONS

Aston Training Center. P. O. Box 3568, Incline Village, NV
89450. (775) 831-8228. Astonpat@aol.com <http://
www.aston-patterning.com>.

Tish Davidson, A.M.

Post-testing, when pre-testing movements are
repeated, allowing the client to feel the changes that
have taken place and integrate them into daily life.

Aston-Patterning requires more participation
from the client than many bodywork techniques. The
massage aspect of Aston-Patterning is designed
around a three-dimensional, non-compressive touch
that releases patterns of tension in the body. It is
gentler than Rolfing. Myokinetics uses touch to
release tension in the face and neck. Arthrokinetics
addresses tension at bones and joints. This massage
is accompanied by education about how new movement patterns may be established.
In addition to Aston-Patterning sessions, clients
are also helped to examine their environment for factors, such as seating or sleeping arrangements, that
may limit their body function and introduce tension.
Finally, they may choose to participate in the Aston
fitness training program that includes loosening techniques based on self-massage, toning, stretching, and
cardiovascular fitness.

Preparations
No special preparation need be taken.

Precautions
No special precautions are necessary when
participating.

Side effects
No undesirable side effects are reported. Usually
clients report a diminution of tension, improved body
movement, and an enhanced feeling of well being.

Research and general acceptance
Aston-Patterning is an outgrowth of Rolfing,
which has been shown to be of benefit in a limited
number of controlled studies. Little controlled
research has been done on the either benefits or
GALE ENCYCLOPEDIA OF MEDICINE

Astrocytoma see Brain tumor

I Ataxia-telangiectasia
Definition
Ataxia-telangiectasia (A-T), also called Louis-Bar
syndrome, is a rare, genetic neurological disorder of
childhood that progressively destroys part of the
motor control area of the brain, leading to a lack of
balance and coordination. A-T also affects the
immune system and increases the risk of leukemia
and lymphoma in affected individuals.

Description
The disorder first appeared in the medical literature in the mid-1920s, but was not named specifically
until 1957. The name is a combination of two recognized abnormalities: ataxia (lack of muscle control)
and telangiectasia (abnormal dilatation of capillary
vessels that often result in tumors and red skin lesions).
However, A-T involves more than just the sum of
these two findings. Other associated A-T problems
include immune system deficiencies, extreme sensitivity to radiation, and blood cancers.
Medical researchers initially suspected that multiple genes (the units responsible for inherited features)
were involved. However, in 1995, mutations in a single
large gene were identified as causing A-T. Researchers
named the gene ATM for A-T, mutated. Subsequent
research revealed that ATM has a significant role in
regulating cell division. The symptoms associated with
A-T reflect the main role of the AT gene, which is to
induce several cellular responses to DNA damage,
such as preventing damaged DNA from being reproduced. When the AT gene is mutated into ATM, the
433

Ataxia-telangiectasia

KEY TERMS

Ataxia-telangiectasia

KEY TERMS
Angioma—A tumor (such as a hemangioma or lymphangioma) that mainly consists of blood vessels or
lymphatic vessels.
Antibody—Any of a large number of proteins produced by specialized blood cells after stimulation by
an antigen and that act specifically against the antigen in an immune response.
Antigen—Any substance (such as a toxin or enzyme)
capable of stimulating an immune response in the
body.
Ataxia—The inability to control voluntary muscle
movement, most frequently resulting from disorders
in the brain or spinal cord.
Autosomal—Relating to any of the chromosomes
except for X and Y, the sex chromosomes.
Cerebellum—The part of the brain responsible for
coordination of voluntary movements.
Gamma-globulin—An extract of human blood that
contains antibodies.
Immune response—A response from the body to an
antigen that occurs when the antigen is identified as
foreign and that induces the production of antibodies
and lymphocytes capable of destroying the antigen
or making it harmless.

signaling networks are affected and the cell no longer
responds correctly to minimize the damage.
A-T is very rare, but it occurs in every population world wide, with an estimated frequency of
between 1/40,000 and 1/100,000 live births. But it
is believed that many A-T cases, particularly those
who die at a young age, are never properly diagnosed. Therefore, this disease may actually be
much more prevalent. According to the A-T
Project Foundation, an estimated 1% (2.5 million
in the United States) of the general population
carries defective A-T genes. Carriers of one copy
of this gene do not develop A-T, but have a significantly increased risk of cancer. This makes the
A-T gene one of the most important cancer-related
genes identified to date.

Causes and symptoms
The ATM gene is autosomal recessive, meaning
the disease occurs only if a defective gene is inherited from both parents. Infants with A-T initially
434

Immunoglobulin—A protein in the blood that is the
component part of an antibody.
Leukemia—A cancer of blood cells characterized by
the abnormal increase in the number of white blood
cells in the tissues. There are many types of leukemias and they are classified according to the type of
white blood cell involved.
Lymphoma—A blood cancer in which lymphocytes,
a variety of white blood cells, grow at an unusually
rapid rate.
Mutation—Any change in the hereditary material of
genes.
Purkinje’s cells—Large branching cells of the nervous
system.
Recessive—Producing little or no phenotypic effect
when occurring in heterozygous condition with a
contrasting allele.
Telangiectases—Spidery red skin lesions caused by
dilated blood vessels.
Telangiectasia—Abnormal dilation of capillary blood
vessels leading to the formation of telangiectases or
angiomas.
Thymus—A gland located in the front of the neck that
coordinates the development of the immune system.

often appear very healthy. At around age two,
ataxia and nervous system abnormalities becomes
apparent. The root cause of A-T-associated ataxia
is cell death in the brain, specifically the large
branching cells of the nervous system (Purkinje’s
cells) which are located in the cerebellum. A toddler becomes clumsy, loses balance easily and lacks
muscle control. Speech becomes slurred and more
difficult, and the symptoms progressively worsen.
Between ages two and eight, telangiectases, or tiny,
red ‘‘spider’’ veins, appear on the cheeks and ears
and in the eyes.
By age 10-12, children with A-T can no longer
control their muscles. Immune system deficiencies
become common, and affected individuals are extremely sensitive to radiation. Immune system deficiencies vary between individuals but include
lower-than-normal levels of proteins that function
as antibodies (immunoglobulins) and white blood
cells (blood cells not containing ‘‘iron’’ proteins).
The thymus gland, which aids in development of
the body’s immune system, is either missing or has
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Diagnosis relies on recognizing the hallmarks
of A-T: progressive ataxia and telangiectasia.
However, this may be difficult as ataxia symptoms
do appear prior to telangiectasia symptoms by several years. Other symptoms can vary between individuals; for example, 70% of individuals with A-T
have a high incidence of respiratory infection, 30%
do not. The identification of the ATM gene raises
hopes that screening, and perhaps treatment, may
be possible.

Treatment
There is currently no cure for A-T, and treatment
focuses on managing the individual’s multiple symptoms. Physical therapy and speech therapy can help
the patient adjust to ataxia. Injections of gamma globulin, or extracts of human blood that contain antibodies, are used to strengthen the weakened immune
system. High-dose vitamin administrations may also
be prescribed. Research continues in many countries
to find effective treatments. Individuals and families
living with this disorder may benefit from attending
support groups.

Prognosis
A-T is a fatal condition. Children with A-T
become physically disabled by their early teens and
typically die by their early 20s, usually from the associated blood cancers and malignancies. In very rare
cases, individuals with A-T may experience slower
progression and a slightly longer life span, surviving
into their 30s. A-T carriers have a five-fold higher risk
than non-carriers of developing certain cancers, especially breast cancer.

Prevention
Medical researchers are investigating methods for
screening individuals who may be carriers of the
GALE ENCYCLOPEDIA OF MEDICINE

defective gene. Prenatal testing for A-T is possible
but not done routinely, because commercial screening
tests have yet to be developed.

Ataxia see Movement disorders

I Atelectasis
Definition
Atelectasis is a collapse of lung tissue affecting
part or all of one lung. This condition prevents normal
oxygen absoption to healthy tissues.

Description
Atelectasis can result from an obstruction (blockage) of the airways that affects tiny air scas called
alveoli. Alveoli are very thin-walled and contain a
rich blood supply. They are important for lung function, since their purpose is the exchange of oxygen and
carbon dioxide. When the airways are blocked by a
mucous ‘‘plug,’’ foreign object, or tumor, the alveoli
are unable to fill with air and collapse of lung tissue
can occur in the affected area. Atelectasis is a potential
complication following surgery, especially in individuals who have undergone chest or abdominal operations resulting in associated abdominal or chest pain
during breathing. Congenital atelectasis can result
from a failure of the lungs to expand at birth. This
congenital condition may be localized or may affect all
of both lungs.

Causes and symptoms
Causes of atelectasis include insufficient attemps
at respiration by the newborn, bronchial obstruction,
or absence of surfactant (a substance secreted by
alveoli that maintains the stability of lung tissue by
reducing the surface tension of fluids that coat the
lung). This lack of surfactant reduces the surface
area available for effective gas exchange causing it to
collapse if severe. Pressure on the lung from fluid or air
can cause atelectasis as well as obstruction of lung air
passages by thick mucus resulting from various infections and lung diseases. Tumors and inhaled objects
can also cause obstruction of the airway, leading to
atelectasis.
Anyone undergoing chest or abdominal surgery
using general anesthesia is at risk to develop atelectasis, since breathing is often shallow after surgery to
435

Atelectasis

developed abnormally. Intelligence is normal, but
growth may be retarded owing to immune system
or hormonal deficiencies. Individuals with A-T are
also sometimes afflicted with diabetes, prematurely
graying hair, and difficulty swallowing. As the children grow older, the immune system becomes
weaker and less capable of fighting infection. In
the later stages, recurrent respiratory infections
and blood cancers, such as leukemia or lymphoma,
are common.

Atelectasis

KEY TERMS
Alveoli—Tiny air sacs in the lungs where gas
exchange takes place between alveolar air and
pulmonary blood within the capillaries
Bronchial—Relating to the air passages to and from
the lungs including the bronchi and the bronchioles.
Bronchoscopy—A procedure in which a hollow,
flexible tube is inserted into the airway to allow
visual examination of the larynx, trachea, bronchi,
and bronchioles. It is also used to collect specimens for
biopsy or culturing and to remove airway obstructions.
Incentive spirometer—A breathing device that
provides feedback on performance to encourage
deep breathing.
Mucus—A thin, slippery film secreted by the
mucous membranes and glands.
A computed tomography (CT) scan through a patient’s chest.
The collapsed lung appears at the right of the image. (Photo
Researchers, Inc. Reproduced by permission.)

avoid pain from the surgical incision. Any significant
decrease in airflow to the alveoli contributes to pooling of secretions, which in turn can cause infection.
Chest injuries causing shallow breathing, including
fractured ribs, can cause atelectasis. Common symptoms of atelectasis include shortness of breath and
decreased chest wall expansion. If atelectasis only
afects a small area of the lung, symptoms are ususally
minimal. If the condition affects a large area of the
lung and develops quickly, the individual may turn
blue (cyanotic) or pale, have extreme shortness of
breath, and feel a stabbing pain on the affected side.
Fever and increased heart rate may be present if infection accompanies atelectasis.

Diagnosis
To diagnose atelectasis, a doctor starts by recording the patient’s symptoms and performing a thorough physical examination. When the doctor listens
to the lungs through a stethoscope (ausculation),
diminished or bronchial breath sounds may be heard.
By tapping on the chest (percussion) while listening
through the stethoscope, the doctor can often tell if the
lung is collapsed. A chest x ray that shows an airless
area in the lung confirms the diagnosis of atelectasis. If
an obstruction of the airways is suspected, a computed
tomography scan (CT) or bronchoscopy may be
performed to locate the cause of the blockage.
436

Postural drainage—Techniques to help expel excess
mucus by specific poistions of the body (that decrease
the effects of gravity) combined with manual percussion and vibration over various parts of the lung.
Surfactant—A substance secreted by the alveoli in
the lungs that reduces the surface tension of lung
fluids, allowing gas exchange and helping maintain
the elasticity of lung tissue.
Tumor—An abnormal growth of tissue resulting from
uncontrolled, progressive multiplication of cells.

Treatment
If atelectasis is due to obstruction of the airway,
the first step in treatment is to remove the cause of
the blockage. This may be done by coughing, suctioning, or bronchoscopy. If a tumor is the cause of atelectasis, surgery may be necessary to remove it.
Antibiotics are commonly used to fight the infection
that often accompanies atelectasis. In cases where
recurrent or long-lasting infection is disabling or
where significant bleeding occurs, the affected section
of the lung may be surgically removed.

Prognosis
If atelectasis is caused by a thick mucus ‘‘plug’’ or
inhaled foreign object, the patient usually recovers completely when the blockage is removed. If it is caused by a
tumor, the outcome depends on the nature of the tumor
involved. If atelectasis is a result of surgery, other postoperative conditions and/or complications affect the
prognosis.
GALE ENCYCLOPEDIA OF MEDICINE

When recovering from surgery, frequent repositioning in bed along with coughing and deep breathing are
important. Coughing and breathing deeply every one to
two hours after any surgical operation with general
anesthesia is recommended. Breathing exercises and the
use of breathing devices, such as an incentive spirometer,
may also help prevent atelectasis. Although smokers
have a higher risk of developing atelectasis following
surgery, stopping smoking six to eight weeks before surgery can help reduce the risk. Increasing fluid intake
during respiratory illness or after surgery (by mouth or
intravenously) helps lung secretions to remain loose.
Increasing humidity may also be beneficial.
Postural drainage techniques can be learned from
a respiratory therapist or physical therapist and are a
useful tool for anyone affected with a respiratiory illness that could cause atelectasis. Because foreign
objects blocking the airway can cause atelectasis, it is
very important to keep small objects that might be
inhaled away from young children.
Resources
ORGANIZATIONS

National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Jeffrey P. Larson, RPT

Atenolol see Beta blockers

I Atherectomy
Definition
Atherectomy is a non-surgical procedure to open
blocked coronary arteries or vein grafts by using a device
on the end of a catheter to cut or shave away atherosclerotic plaque (a deposit of fat and other substances
that accumulate in the lining of the artery wall).

Purpose
Atherectomy is performed to restore the flow of
oxygen-rich blood to the heart, to relieve chest pain,
and to prevent heart attacks. It may be done on
patients with chest pain who have not responded to
other medical therapy and on certain of those who are
candidates for balloon angioplasty (a surgical procedure in which a balloon catheter is used to flatten
GALE ENCYCLOPEDIA OF MEDICINE

plaque against an artery wall) or coronary artery
bypass graft surgery. It is sometimes performed to
remove plaque that has built up after a coronary artery
bypass graft surgery.

Precautions
Atherectomy should not be performed when the
plaque is located where blood vessels divide into
branches, when plaque is angular or inside an angle
of a blood vessel, on patients with weak vessel walls,
on ulcerated or calcium-hardened lesions, or on
blockages through which a guide wire won’t pass.

Description
Atherectomy uses a rotating shaver or other device
placed on the end of a catheter to slice away or destroy
plaque. At the beginning of the procedure, medications
to control blood pressure, dilate the coronary arteries,
and prevent blood clots are administered. The patient is
awake but sedated. The catheter is inserted into an
artery in the groin, leg, or arm, and threaded through
the blood vessels into the blocked coronary artery. The
cutting head is positioned against the plaque and activated, and the plaque is ground up or suctioned out.
The types of atherectomy are rotational, directional, and transluminal extraction. Rotational atherectomy uses a high speed rotating shaver to grind up
plaque. Directional atherectomy was the first type
approved, but is no longer commonly used; it scrapes
plaque into an opening in one side of the catheter.
Transluminal extraction coronary atherectomy uses a
device that cuts plaque off vessel walls and vacuums it
into a bottle. It is used to clear bypass grafts.
Performed in a cardiac catheterization lab, atherectomy is also called removal of plaque from the coronary
arteries. It can be used instead of, or along with, balloon
angioplasty. Atherectomy is successful about 95% of the
time. Plaque forms again in 20-30% of patients.

Preparation
The day before atherectomy, the patient takes
medication to prevent blood clots and may be asked
to bathe and shampoo with an antiseptic skin cleaner.

Aftercare
After the procedure, the patient spends several days
in the hospital’s cardiac monitoring area. For at least
20 minutes, pressure is applied to a dressing on the
insertion site. For the first hour, an electrocardiogram
and close monitoring are conducted; vital signs are
437

Atherectomy

Prevention

Atherectomy
In this digitized ultrasound of a blood vessel, C is the catheter, D is the dissection, and F is the artherosclerotic flap. (Custom
Medical Stock Photo. Reproduced by permission.)

Risks

KEY TERMS
Atherosclerotic plaque—A deposit of fat and other
substances that accumulate in the lining of the
artery wall.
Balloon angioplasty—A surgical procedure in
which a balloon catheter is used to flatten plaque
against an artery wall.
Coronary arteries—The two main arteries that provide blood to the heart. The coronary arteries surround the heart like a crown, coming out of the
aorta, arching down over the top of the heart, and
dividing into two branches. These are the arteries
where coronary artery disease occurs.
Hematoma—A localized collection of blood, usually
clotted, due to a break in the wall of blood vessel.

checked every 15 minutes. Pain medication is then
administered. The puncture site is checked once an
hour or more. For most of the first 24 hours, the patient
remains in bed.
438

Chest pain is the most common complication of
atherectomy. Other common complications are injury
to the blood vessel lining, plaque that re-forms, blood
clots (hematoma), and bleeding at the site of insertion.
More serious but less frequent complications are
blood vessel holes, blood vessel wall tears, or reduced
blood flow to the heart.
Resources
BOOKS

McPhee, Stephen, et al., editors. Current Medical Diagnosis
and Treatment, 1998. 37th ed. Stamford: Appleton &
Lange, 1997.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Atherosclerosis is the build up of a waxy plaque
on the inside of blood vessels. In Greek, athere means
gruel, and skleros means hard. Atherosclerosis is often
called arteriosclerosis. Arteriosclerosis (from the
Greek arteria, meaning artery) is a general term for
hardening of the arteries. Arteriosclerosis can occur in
several forms, including atherosclerosis.

Description
Atherosclerosis, a progressive process responsible
for most heart disease, is a type of arteriosclerosis
or hardening of the arteries. An artery is made up of
several layers: an inner lining called the endothelium,
an elastic membrane that allows the artery to expand
and contract, a layer of smooth muscle, and a layer of
connective tissue. Arteriosclerosis is a broad term that
includes a hardening of the inner and middle layers of
the artery. It can be caused by normal aging, by high
blood pressure, and by diseases such as diabetes.
Atherosclerosis is a type of arteriosclerosis that affects
only the inner lining of an artery. It is characterized by
plaque deposits that block the flow of blood.
Plaque is made of fatty substances, cholesterol,
waste products from the cells, calcium, and fibrin, a
stringy material that helps clot blood. The plaque formation process stimulates the cells of the artery wall to
produce substances that accumulate in the inner layer.
Fat builds up within these cells and around them, and
they form connective tissue and calcium. The inner
layer of the artery wall thickens, the artery’s diameter
is reduced, and blood flow and oxygen delivery are
decreased. Plaques can rupture or crack open, causing
the sudden formation of a blood clot (thrombosis).
Atherosclerosis can cause a heart attack if it completely
blocks the blood flow in the heart (coronary) arteries. It
can cause a stroke if it completely blocks the brain
(carotid) arteries. Atherosclerosis can also occur in the
arteries of the neck, kidneys, thighs, and arms, causing
kidney failure or gangrene and amputation.

Risk factors that can be changed:


Cigarette/tobacco smoke–Smoking increases both
the chance of developing atherosclerosis and the
chance of dying from coronary heart disease.
Second hand smoke may also increase risk.



High blood cholesterol–Cholesterol, a soft, waxy
substance, comes from foods such as meat, eggs,
and other animal products and is produced in the
liver. Age, sex, heredity, and diet affect cholesterol.
Total blood cholesterol is considered high at levels
above 240 mg/dL and borderline at 200-239 mg/dL.
High-risk levels of low-density lipoprotein (LDL
cholesterol) begin at 130-159 mg/dL.



High triglycerides–Most fat in food and in the body
takes the form of triglycerides. Blood triglyceride
levels above 400 mg/dL have been linked to coronary
artery disease in some people. Triglycerides, however, are not nearly as harmful as LDL cholesterol.



High blood pressure–Blood pressure of 140 over 90
or higher makes the heart work harder, and over
time, both weakens the heart and harms the arteries.



Physical inactivity–Lack of exercise increases the
risk of atherosclerosis.



Diabetes mellitus–The risk of developing atherosclerosis is seriously increased for diabetics and can be lowered by keeping diabetes under control. Most diabetics
die from heart attacks caused by atherosclerosis.



Obesity–Excess weight increases the strain on the
heart and increases the risk of developing atherosclerosis even if no other risk factors are present.

Causes and symptoms
Atherosclerosis can begin in the late teens, but it
usually takes decades to cause symptoms. Some people
experience rapidly progressing atherosclerosis during
their thirties, others during their fifties or sixties.
Atherosclerosis is complex. Its exact cause is still
unknown. It is thought that atherosclerosis is caused
GALE ENCYCLOPEDIA OF MEDICINE

Risk factors that cannot be changed:


Heredity–People whose parents have coronary
artery disease, atherosclerosis, or stroke at an early
439

Atherosclerosis

I Atherosclerosis

by a response to damage to the endothelium from high
cholesterol, high blood pressure, and cigarette smoking.
A person who has all three of these risk factors is eight
times more likely to develop atherosclerosis than is a
person who has none. Physical inactivity, diabetes, and
obesity are also risk factors for atherosclerosis. High
levels of the amino acid homocysteine and abnormal
levels of protein-coated fats called lipoproteins also
raise the risk of coronary artery disease. These substances are the targets of much current research. The
role of triglycerides, another fat that circulates in the
blood, in forming atherosclerotic plaques is unclear.
High levels of triglycerides are often associated with
diabetes, obesity, and low levels of high-density lipoproteins (HDL cholesterol). The more HDL (‘‘good’’)
cholesterol, in the blood, the less likely is coronary
artery disease. These risk factors are all modifiable.
Non-modifiable risk factors are heredity, sex, and age.

Atherosclerosis

Lining of
artery

High cholesterol levels,
high blood pressure,
diabetes, obesity, viruses,
cigarette smoking, etc.,
cause injuries to the
lining of the artery,
creating areas where
higher levels of lipids
are trapped.

Monocyte

Muscle
T-cell

Monocytes (the largest of the
white blood cells) and T-cells
are attracted to the injury.

Monocytes, which become
macrophages when they leave
the bloodstream, and T-cells
penetrate the lining of the artery.
The macrophages soak up lipids,
becoming large foam cells and
distorting the inner surface of the
artery. Blood flow becomes
restricted.

Foam cell

Platelets

The result is a fibrous
lesion, made up in part
of muscle cells, proteins,
and collagen, that has at
its center a pool of lipids
and dead cells. Blood
flow can be very nearly
cut off by the blockage.

Further injury is inflicted by foam cells
attempting to remove lipids back to the
lungs, liver, spleen and lymph nodes
by again passing through the lining of
the artery.

When the arterial lining becomes
separated over the growing mass of
foam cells, platelets are attracted to the
site and begin the process of clot formation.

The progression of atherosclerosis. (Illustration by Hans & Cassady.)

age are at increased risk. The high rate of severe
hypertension among African-Americans puts them
at increased risk.




Sex–Before age 60, men are more likely to have heart
attacks than women are. After age 60, the risk is
equal among men and women.
Age–Risk is higher in men who are 45 years of age and
older and women who are 55 years of age and older.

Symptoms differ depending upon the location of
the atherosclerosis.


In the coronary (heart) arteries: Chest pain, heart
attack, or sudden death.



In the carotid (brain) arteries: Sudden dizziness,
weakness, loss of speech, or blindness.

440



In the femoral (leg) arteries: Disease of the blood
vessels in the outer parts of the body (peripheral
vascular disease) causes cramping and fatigue in the
calves when walking.



In the renal (kidney) arteries: High blood pressure
that is difficult to treat.

Diagnosis
Physicians may be able to make a diagnosis of
atherosclerosis during a physical exam by means of a
stethoscope and gentle probing of the arteries with the
hand (palpation). More definite tests are electrocardiography, echocardiography or ultrasonography of the
arteries (for example, the carotids), radionuclide
scans, and angiography.
GALE ENCYCLOPEDIA OF MEDICINE

Arteriosclerosis—Hardening of the arteries. It
includes atherosclerosis, but the two terms are
often used synonymously.
Cholesterol—A fat-like substance that is made by
the human body and eaten in animal products.
Cholesterol is used to form cell membranes and
process hormones and vitamin D. High cholesterol
levels contribute to the development of
atherosclerosis.
HDL Cholesterol—About one-third or one-fourth
of all cholesterol is high-density lipoprotein cholesterol. High levels of HDL, nicknamed ‘‘good’’ cholesterol, decrease the risk of atherosclerosis.
LDL Cholesterol—Low-density lipoprotein cholesterol is the primary cholesterol molecule. High
levels of LDL, nicknamed ‘‘bad’’ cholesterol,
increase the risk of atherosclerosis
Plaque—A deposit of fatty and other substances
that accumulates in the lining of the artery wall.
Triglyceride—A fat that comes from food or is
made from other energy sources in the body.
Elevated triglyceride levels contribute to the development of atherosclerosis.

An electrocardiogram shows the heart’s activity.
Electrodes covered with conducting jelly are placed on
the patient’s body. They send impulses of the heart to a
recorder. The test takes about 10 minutes and is performed in a physician’s office. Exercise electrocardiography (stress test) is conducted while the patient
exercises on a treadmill or a stationary bike. It is
performed in a physician’s office or an exercise laboratory and takes 15-30 minutes.
Echocardiography, cardiac ultrasound, uses sound
waves to create an image of the heart’s chambers and
valves. A technician applies gel to a hand-held transducer, presses it against the patient’s chest, and images are
displayed on a monitor. This technique cannot evaluate
the coronary arteries directly. They are too small and
are in motion with the heart. Severe coronary artery
disease, however, may cause abnormal heart motion
that is detected by echocardiography. Performed in a
cardiology outpatient diagnostic laboratory, the test
takes 30-60 minutes. Ultrasonography is also used to
assess arteries of the neck and thighs.
Radionuclide angiography and thallium (or sestamibi) scanning enable physicians to see the blood
GALE ENCYCLOPEDIA OF MEDICINE

flow through the coronary arteries and the heart
chambers. Radioactive material is injected into the
bloodstream. A device that uses gamma rays to
produce an image of the radioactive material
(gamma camera) records pictures of the heart.
Radionuclide angiography is usually performed in
a hospital’s nuclear medicine department and takes
30-60 minutes. Thallium scanning is usually done
after an exercise stress test or after injection of a
vasodilator, a drug to enlarge the blood vessels, like
dipyridamole (Persantine). Thallium is injected, and
the scan is done then and again four hours (and
possibly 24 hours) later. Thallium scanning is
usually performed in a hospital’s nuclear medicine
department. Each scan takes 30-60 minutes.
Coronary angiography is the most accurate diagnostic method and the only one that requires entering
the body (invasive procedure). A cardiologist inserts a
catheter equipped with a viewing device into a blood
vessel in the leg or arm and guides it into the heart. The
patient has been given a contrast dye that makes
the heart visible to x rays. Motion pictures are taken
of the contrast dye flowing though the arteries.
Plaques and blockages, if present, are well defined.
The patient is awake but has been given a sedative.
Coronary angiography is performed in a cardiac
catheterization laboratory and takes from 30 minutes
to two hours.

Treatment
Treatment includes lifestyle changes, lipid-lowering drugs, percutaneous transluminal coronary angioplasty, and coronary artery bypass surgery.
Atherosclerosis requires lifelong care.
Patients who have less severe atherosclerosis may
achieve adequate control through lifestyle changes
and drug therapy. Many of the lifestyle changes that
prevent disease progression–a low-fat, low-cholesterol
diet, losing weight (if necessary), exercise, controlling
blood pressure, and not smoking–also help prevent the
disease.
Most of the drugs prescribed for atherosclerosis
seek to lower cholesterol. Many popular lipid-lowering drugs can reduce LDL-cholesterol by an average
of 25-30% when combined with a low-fat, lowcholesterol diet. Lipid-lowering drugs include bile
acid resins, ‘‘statins’’ (drugs that effect HMG-CoA
reductase, an enzyme that controls the processing of
cholesterol), niacin, and fibric acid derivatives such as
gemfibrozil (Lobid). Aspirin helps prevent thrombosis
and a variety of other medications can be used to treat
the effects of atherosclerosis.
441

Atherosclerosis

KEY TERMS

Atherosclerosis

Percutaneous transluminal coronary angioplasty
and bypass surgery are invasive procedures that
improve blood flow in the coronary arteries.
Percutaneous transluminal coronary angioplasty (coronary angioplasty) is a non-surgical procedure in
which a catheter tipped with a balloon is threaded
from a blood vessel in the thigh into the blocked
artery. The balloon is inflated, compresses the plaque
to enlarge the blood vessel, and opens the blocked
artery. Coronary angioplasty is performed by a cardiologist in a hospital and generally requires a hospital
stay of one or two days. It is successful about 90% of
the time, but for one-third of patients the artery narrows again within six months. It can be repeated and a
‘‘stent’’ may be placed in the artery to help keep it open
(see below).
In coronary artery bypass surgery (bypass surgery), a detour is built around the blockage with a
healthy vein or artery, which then supplies oxygenrich blood to the heart. It is major surgery appropriate
for patients with blockages in two or three major
coronary arteries or severely narrowed left main coronary arteries, and for those who have not responded
to other treatments. It is performed in a hospital under
general anesthesia and uses a heart-lung machine.
About 70% of patients experience full relief; about
20% partial relief.
Three other semi-experimental surgical procedures may be used to treat atherosclerosis. In atherectomy, a cardiologist shaves off and removes strips
of plaque from the blocked artery. In laser angioplasty, a catheter with a laser tip is inserted to burn
or break down the plaque. A metal coil called a
stent may be permanently implanted to keep a
blocked artery open.

garlic is recommended, as is eating raw and cooked
fish, especially cold-water fish like salmon. Smoking,
alcohol, and stimulants like coffee should be avoided.
Chelation therapy, which uses anticoagulant drugs and
nutrients to dissolve plaque and flush it through the
kidneys, is controversial. Long-term remedies can be
prescribed by specialists in ayurvedic medicine, which
combines diet, herbal remedies, relaxation and exercise, and homeopathy, which treats a disease with
small doses of a drug that causes the symptoms of
the disease.

Prognosis
Atherosclerosis can be successfully treated but not
cured. Recent clinical studies have shown that atherosclerosis can be delayed, stopped, and even reversed by
aggressively lowering LDL cholesterol. New diagnostic techniques enable physicians to identify and treat
atherosclerosis in its earliest stages. New technologies
and surgical procedures have extended the lives of
many patients who would otherwise have died.
Research continues.

Prevention
A healthy lifestyle–eating right, regular exercise,
maintaining a healthy weight, not smoking, and controlling hypertension–can reduce the risk of developing atherosclerosis, help keep the disease from
progressing, and sometimes cause it to regress.


Eat right-A healthy diet reduces excess levels of LDL
cholesterol and triglycerides. It includes a variety of
foods that are low in fat and cholesterol and high in
fiber; plenty of fruits and vegetables; and limited
sodium. Fat should comprise no more than 30%,
and saturated fat no more than 8-10%, of total
daily calories according to the American Heart
Association. Cholesterol should be limited to about
300 milligrams per day and sodium to about 2,400
milligrams. The ‘‘Food Guide’’ Pyramid developed
by the U.S. Departments of Agriculture and Health
and Human Services provides daily guidelines: 6-11
servings of bread, cereal, rice, and pasta; 3-5 servings
of vegetables; 2-4 servings of fruit; 2-3 servings of
milk, yogurt, and cheese; and 2-3 servings of meat,
poultry, fish, dry beans, eggs, and nuts. Fats, oils,
and sweets should be used sparingly. Mono-unsaturated oils, like olive and rapeseed (Canola) are good
alternatives to use for cooking.



Exercise regularly–Aerobic exercise can lower blood
pressure, help control weight, and increase HDL
(‘‘good’’) cholesterol. It may keep the blood vessels

Alternative treatment
Alternative therapies that focus on diet and lifestyle can help prevent, retard, or reverse atherosclerosis. Herbal therapies that may be helpful include:
hawthorn (Crataegus laevigata), notoginseng root
(Panax notoginseng), garlic (Allium sativum), ginger
(Zingiber officinale), hot red or chili peppers, yarrow
(Achillea millefolium), and alfalfa (Medicago sativum).
Relaxation techniques including yoga, meditation,
guided imagery, biofeedback, and counseling and
other ‘‘talking’’ therapies may also be useful to prevent
or slow the progress of the disease. Dietary modifications focus on eating foods that are low in fats (especially saturated fats), cholesterol, sugar, and animal
proteins and high in fiber and antioxidants (found in
fresh fruits and vegetables). Liberal use of onions and
442

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Maintain a desirable body weight–Losing weight can
help reduce total and LDL cholesterol, reduce triglycerides, and boost HDL cholesterol. It may also
reduce blood pressure. Eating right and exercising
are two key components in maintaining a desirable
body weight.
Do not smoke or use tobacco–Smoking has many
adverse effects on the heart but quitting can repair
damage. Ex-smokers face the same risk of heart disease as non-smokers within five to 10 years of quitting. Smoking is the worst thing a person can do to
their heart and lungs.
Seek treatment for hypertension–High blood pressure can be controlled through lifestyle changes–
reducing sodium and fat, exercising, managing
stress, quitting smoking, and drinking alcohol in
moderation–and medication. Drugs that provide
effective treatment are: diuretics, beta-blockers, sympathetic nerve inhibitors, vasodilators, angiotensin
converting enzyme inhibitors, and calcium antagonists. Hypertension usually has no symptoms so it
must be checked to be known. Like cholesterol,
hypertension is called a ‘‘silent killer.’’

Resources
PERIODICALS

Morgan, Peggy. ‘‘What Your Heart Wishes You Knew
About Cholesterol.’’ Prevention (September 1997): 96.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto

Athetosis see Movement disorders
GALE ENCYCLOPEDIA OF MEDICINE

I Athlete’s foot
Definition
A common fungus infection between the toes in
which the skin becomes itchy and sore, cracking and
peeling away. Athlete’s foot (also known as tinea pedis
or foot ringworm) can be treated, but it can be tenacious and difficult to clear up completely.

Description
Athlete’s foot is a very common condition of
itchy, peeling skin on the feet. In fact, it’s so common
that most people will have at least one episode at least
once in their lives. It’s less often found in women and
children under age 12. (Symptoms that look like athlete’s foot in young children most probably are caused
by some other skin condition).
Because the fungi grow well in warm, damp areas,
they flourish in and around swimming pools, showers,
and locker rooms. Tinea pedis got its common name
because the infection was common among athletes
who often used these areas.

Causes and symptoms
Athlete’s foot is caused by a fungal infection that
most often affects the fourth and fifth toe webs.
Trichophyton rubrum, T. mentagrophytes, and
Epidermophyton floccosum, the fungi that cause athlete’s foot, are unusual in that they live exclusively on
dead body tissue (hair, the outer layer of skin, and
nails). The fungus grows best in moist, damp, dark
places with poor ventilation. The problem doesn’t
occur among people who usually go barefoot.
Many people carry the fungus on their skin.
However, it will only flourish to the point of causing
athlete’s foot if conditions are right. Many people
believe athlete’s foot is highly contagious, especially in
public swimming pools and shower rooms. Research
has shown, however, that it is difficult to pick up the
infection simply by walking barefoot over a contaminated damp floor. Exactly why some people develop
the condition and others don’t is not well understood.
Sweaty feet, tight shoes, synthetic socks that don’t
absorb moisture well, a warm climate, and not drying
the feet well after swimming or bathing, all contribute
to the overgrowth of the fungus.
Symptoms of athlete’s foot include itchy, sore skin
on the toes, with scaling, cracking, inflammation, and
blisters. Blisters that break, exposing raw patches of
443

Athlete’s foot

more flexible. Moderate to intense aerobic exercise
lasting about 30 minutes (or three 10-minute exercise
periods) four or more times per week is recommended, according to the Centers for Disease
Control and Prevention and the American College
of Sports Medicine. Aerobic exercise includes walking, jogging, and cycling, active gardening, climbing
stairs, or brisk housework. A physician should be
consulted before exercise if a person has atherosclerosis or is at increased risk for it.

Athlete’s foot

of skin scrapings under a microscope. This test, called
a KOH preparation, treats a sample of tissue scraped
from the infected area with heat and potassium hydroxide (KOH). This treatment dissolves certain substances in the tissue sample, making it possible to see
the fungi under the microscope.

Treatment

Athlete’s foot fungus on toes of patient. (Custom Medical Stock
Photo. Reproduced by permission.)

Athlete’s foot may be resistant to medication and
should not be ignored. Simple cases usually respond
well to antifungal creams or sprays (clotrimazole, ketoconazole, miconazole nitrate, sulconazole nitrate, or
tolnaftate). If the infection is resistant to topical treatment, the doctor may prescribe an oral antifungal drug.
Untreated athlete’s foot may lead to a secondary
bacterial infection in the skin cracks.

Alternative treatment
A footbath containing cinnamon has been shown
to slow down the growth of certain molds and fungi,
and is said to be very effective in clearing up athlete’s
foot. To make the bath:

Athlete’s foot fungus on bottom of patient’s foot. (Custom
Medical Stock Photo. Reproduced by permission.)

tissue, can cause pain and swelling. As the infection
spreads, itching and burning may get worse.
If it’s not treated, athlete’s foot can spread to the
soles of the feet and toenails. Stubborn toenail infections
may appear at the same time, with crumbling, scaling and
thickened nails, and nail loss. The infection can spread
further if patients scratch and then touch themselves
elsewhere (especially in the groin or under the arms).
It’s also possible to spread the infection to other parts
of the body via contaminated bed sheets or clothing.



heat four cups of water to a boil



add eight to 10 broken cinnamon sticks



reduce heat and simmer five minutes



remove and let the mixture steep for 45 minutes until
lukewarm



soak feet

Other herbal remedies used externally to treat
athlete’s foot include: a foot soak or powder containing goldenseal (Hydrastis canadensis); tea tree oil
(Melaleuca spp.); or calendula (Calendula officinalis)
cream to help heal cracked skin.

Prognosis
Athlete’s foot usually responds well to treatment,
but it is important to take all medication as directed by
a dermatologist, even if the skin appears to be free of
fungus. Otherwise, the infection could return. The toenail infections that may accompany athlete’s foot,
however, are typically very hard to treat effectively.

Diagnosis
Not all foot rashes are athlete’s foot, which is why a
physician should diagnose the condition before any
remedies are used. Using nonprescription products on a
rash that is not athlete’s foot could make the rash worse.
A dermatologist can diagnose the condition by
physical examination and by examining a preparation
444

Prevention
Good personal hygiene and a few simple precautions can help prevent athlete’s foot. To prevent
spread of athlete’s foot:


wash feet daily



dry feet thoroughly (especially between toes)
GALE ENCYCLOPEDIA OF MEDICINE

avoid tight shoes (especially in summer)



wear sandals during warm weather



wear cotton socks and change them often if they get
damp



don’t wear socks made of synthetic material



go barefoot outdoors when possible



wear bathing shoes in public bathing or showering
areas



use a good quality foot powder



don’t wear sneakers without socks



wash towels, contaminated floors, and shower stalls
well with hot soapy water if anyone in the family has
athlete’s foot.

Cardiac enlargement is associated with dynamic training. The heart’s response to static training is hypertrophy, thickening of the muscle walls of the heart. As
the wall of the heart adapts, there are changes in the
electrical conducting system of the heart. Because of
the larger volume of blood being pumped with each
heart beat, the heart rate when at rest decreases
below the normal level for nonathletes.
Sudden unexpected death (SUD) is the death of an
athlete, usually during or shortly after physical activity. Often, there is no warning that the person will
experience SUD, although in some cases, warning
signs appear which cause the person to seek medical
advice. Importantly, cases of death occurring during
physical activity are not caused by athletic heart
syndrome, but by undiagnosed heart disorders.

Resources

Causes and symptoms

BOOKS

Thompson, June, et al. Mosby’s Clinical Nursing. St. Louis:
Mosby, 1998.
ORGANIZATIONS

American Podiatric Medical Association. 9312 Old
Georgetown Road, Bethesda, MD 20814-1698. (301)
571-9200. <http://www.apma.org>.

Carol A. Turkington

Athletic heart syndrome is the consequence of a
normal adaptation by the heart to increased physical
activity. The changes in the electrical conduction system of the heart may be pronounced and diagnostic,
but should not cause problems. In the case of SUD,
other heart problems are involved. In 85-97% of the
cases of SUD, an underlying structural defect of the
heart has been noted.

Diagnosis

I Athletic heart syndrome
Definition
Athletic heart syndrome is the adaptation of
an athlete’s heart in response the physiologic stresses
of strenuous physical training. It can be difficult to
distinguish a significant medical condition from an
athletic heart.

Description
The heart adapts to physical demands by enlarging, especially the left ventricle. Enlargement increases
the cardiac output, the amount of blood pumped with
each beat of the heart. The exact type of adaptation
depends on the nature of the physical demand. There
are two types of demand, static and dynamic. Static
demand involves smaller groups of muscles under
extreme resistance for brief period. An example is
weight lifting. Dynamic training involves larger groups
of muscles at lower resistance for extended periods of
time. Examples are aerobic training and tennis.
GALE ENCYCLOPEDIA OF MEDICINE

The changes in the heart beat caused by the electrical conduction system of the heart are detectable on
an electrocardiogram. Many of the changes seen in
athletic heart syndrome mimic those of various heart
diseases. Careful examination must be made to distinguish heart disease from athletic heart syndrome.

Prognosis
The yearly rate for occurrence of SUD in people
less than 35 years of age is less than 7 incidents per
100,000. Of all SUD cases, only about 8% are exercise
related. On a national basis, this means that each year
approximately 25 athletes experience SUD. In persons
over age 35, the incidence of SUD is approximately 55
in 100,000, with only 3% of the cases occurring during
exercise.
Resources
BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, editors. The
Heart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD
445

Athletic heart syndrome



Atkins diet

I Atkins diet
Definition
The Atkins diet is a high-protein, high-fat, and
very low-carbohydrate regimen. It emphasizes meat,
cheese, and eggs, while discouraging foods such as
bread, pasta, fruit, and sugar. It is a form of ketogenic diet.

Purpose
The primary benefit of the diet is rapid and substantial weight loss. By restricting carbohydrate
intake, the body will burn more fat stored in the
body. Since there are no limits on the amount of
calories or quantities of foods allowed on the diet,
there is little hunger between meals. According to
Atkins, the diet can alleviate symptoms of conditions
such as fatigue, irritability, headaches, depression, and
some types of joint and muscle pain.

Description
The regimen is a low-carbohydrate, or ketogenic
diet, characterized by initial rapid weight loss, usually
due to water loss. Drastically reducing the amount of
carbohydrate intake causes liver and muscle glycogen
loss, which has a strong but temporary diuretic effect.
Long-term weight loss occurs because with a low
amount of carbohydrate intake, the body burns stored
fat for energy.
The four-step diet starts with a two-week induction program designed to rebalance an individual’s
metabolism. Unlimited amounts of fat and protein
are allowed but carbohydrate intake is restricted to
20 grams per day. Foods allowed include butter, oil,
meat, poultry, fish, eggs, cheese, and cream. The daily
amount of carbohydrates allowed equals about three
cups of salad vegetables, such as lettuce, cucumbers,
and celery.
The second stage is for ongoing weight loss. It
allows 20-40 grams of carbohydrates a day. When
the individual is about 10 pounds from their desired
weight, they begin the pre-maintenance phase. This
gradually adds one to three servings a week of high
carbohydrate foods, such as a piece of fruit or slice of
whole-wheat bread. When the desired weight is
reached, the maintenance stage begins. It allows
40-60 grams of carbohydrates per day.
Opinion from the general medical community
remains mixed on the Atkins diet. There have been
no significant long-term scientific studies on the diet.
446

A number of leading medical and health organizations, including the American Medical Association,
American Dietetic Association (ADA), and the
American Heart Association oppose it. It is drastically
different than the dietary intakes recommended by the
U.S. Department of Agriculture and the National
Institutes of Health. Much of the opposition is because
the diet is lacking in some vitamins and nutrients, and
because it is high in fat. In a hearing before the U.S.
Congress on February 24, 2000, an ADA representative called the Atkins diet ‘‘hazardous’’ and said it
lacked scientific credibility.

Preparations
No advance preparation is needed to go on the
diet. However, as with most diets, it is generally considered appropriate to consult with a physician and to
have a physical evaluation before starting such a nutritional regimen. The evaluation should include blood
tests to determine levels of cholesterol, triglycerides,
glucose, insulin, and uric acid. A glucose tolerance test
is also recommended.

Precautions
Adherence to the Atkins diet can result in vitamin
and mineral deficiencies. In his books, Atkins recommends a wide-range of nutritional supplements, including a multi-vitamin. Among his recommendations,
Atkins suggests the following daily dosages: 300-600
micrograms (mcg) of chromium picolinate, 100-400
milligrams (mg) of pantetheine, 200 mcg of selenium,
and 450-675 mcg of biotin.
The diet is not recommended for lacto-ovo vegetarians, since it cannot be done as successfully without
protein derived from animal products. Also, vegans
cannot follow this diet, since a vegan diet is too high in
carbohydrates, according to Atkins. Instead, he
recommends vegetarians with a serious weight problem give up vegetarianism, or at least include fish in
their diet.

Side effects
According to Atkins, the diet causes no adverse
side effects. Many health care professionals disagree. In a fact sheet for the Healthcare Reality
Check Web site (<http://www.hcrc.org>), Ellen
Coleman, a registered dietician and author, said
the diet may have serious side effects for some people. She said complications associated with the diet
include ketosis, dehydration, electrolyte loss, calcium
depletion, weakness, nausea, and kidney problems.
GALE ENCYCLOPEDIA OF MEDICINE

he developed the Atkins Diet in the early 1970s. The diet is
a ketogenic diet—a high protein, high fat, and very low
carbohydrate regimen resulting in ketosis. It emphasizes
meat, cheese, and eggs, while discouraging foods such as
bread, pasta, fruit, and sugar. It first came to public attention in 1972 with the publication of Dr. Atkins’ Diet
Revolution. The book quickly became a bestseller but
unlike most other fad diet books, this one has remained
popular. At last count, it had been reprinted 28 times and
sold more than 10 million copies worldwide. Since then,
Atkins has authored a number of other books on his diet
theme, including Dr. Atkins’ New Diet Revolution (1992),
Dr. Atkins’ Quick and Easy New Diet Cookbook (1997),
and The Vita-Nutrient Solution: Nature’s Answer to Drugs
(1998).

(AP/Wide World Photos. Reproduced by permission.)

Dr. Robert C. Atkins graduated from the University
of Michigan in 1951 and received his medical degree
from Cornell University Medical School in 1955 with a
specialty in cardiology. As an internist and cardiologist

KEY TERMS
Biotin—A B complex vitamin, found naturally in
yeast, liver, and egg yolks.
Carbohydrates—Neutral compounds of carbon,
hydrogen, and oxygen found in sugar, starches,
and cellulose.
Hypertension—Abnormally high arterial blood
pressure, which if left untreated can lead to heart
disease and stroke.

Atkins has seen about 60,000 patients in his more
than 30 years of practice. He has also appeared on numerous radio and television talk shows, has his own syndicated radio program, Your Health Choices, and authors
the monthly newsletter Dr. Atkins’ Health Revelations.
Atkins has received the World Organization of
Alternative Medicine’s Recognition of Achievement
Award and been named the National Health Federation’s
Man of the Year. He was the director of the Atkins Center
for Complementary Medicine which he founded in the
early 1980s until his death. The center is located at 152
E. 55th St., New York, NY 10022.

‘‘It is certainly riskier for overweight individuals with
medical problems such as heart disease, hypertension,
kidney disease, and diabetes than it is for overweight
people with no health problems,’’ she said.
People with diabetes taking insulin are at risk of
becoming hypoglycemic if they do not eat appropriate
carbohydrates. Also, persons who exercise regularly
may experience low energy levels and muscle fatigue
from low carbohydrate intake.
Resources

Ketogenic diet—A diet that supplies an abnormally
high amount of fat, and small amounts of carbohydrates and protein.

BOOKS

Ketosis—An abnormal increase in ketones in the
body, usually found in people with uncontrolled
diabetes mellitus.
Pantetheine—A growth factor substance essential
in humans, and a constituent of coenzyme A.

PERIODICALS

Triglycerides—A blood fat lipid that increases the
risk for heart disease.

GALE ENCYCLOPEDIA OF MEDICINE

Atkins, Dr. Robert C. Dr. Atkins’ Age-Defying Diet
Revolution. New York: St. Martin’s Press. 1999.
Cray, Dan, et al. ‘‘The Low-Carb Diet Craze.’’ Time
November 1, 1999: 72-79.
Gotthardt, Melissa Meyers. ‘‘The New Low-Carb Diet
Craze.’’ Cosmopolitan February 2000: 148.
Merrell, Woodson. ‘‘How I Became a Low-Carb Believer.’’
Time November 1, 1999: 80.
Turner, Richard. ‘‘The Trendy Diet That Sizzles.’’
Newsweek September 6, 1999: 60.
447

Atkins diet

DR.ROBERT C. ATKINS (1930–2003)

Atopic dermatitis

OTHER

Atkins Center for Complementary Medicine. 152 E. 55th St.,
New York, NY 10022. 212-758-2110. <http://
www.atkinscenter.com>.

Ken R. Wells

I Atopic dermatitis
Definition
Eczema is a general term used to describe a variety
of conditions that cause an itchy, inflamed skin
rash. Atopic dermatitis, a form of eczema, is a noncontagious disorder characterized by chronically
inflamed skin and sometimes intolerable itching.

Description
Atopic dermatitis refers to a wide range of diseases that are often associated with stress and allergic
disorders that involve the respiratory system, like
asthma and hay fever. Although atopic dermatitis
can appear at any age, it is most common in children
and young adults. Symptoms usually abate before the
age of 25 and do not affect the patient’s general health.
About one in ten babies develop a form of atopic
dermatitis called infantile eczema. Characterized by skin
that oozes and becomes encrusted, infantile eczema most
often occurs on the face and scalp. The condition usually
improves before the child’s second birthday, and medical
attention can keep symptoms in check until that time.
When atopic dermatitis develops after infancy,
inflammation, blistering, oozing, and crusting are less
pronounced. The patient’s sores become dry, turn from
red to brownish-gray, and skin may thicken and become
scaly. In dark-skinned individuals, this condition can
cause the complexion to lighten or darken. Itching associated with this condition is usually worst at night. It
can be so intense that patients scratch until their sores
bleed, sometimes causing scarring and infection.
Atopic dermatitis affects about 3% of the population of the United States, and about 80% of the people
who have the condition have one or more relatives with
the same condition or a similar one. Symptoms tend to
be most severe in females. Atopic dermatitis can erupt on
any part of the skin, and crusted, thickened patches on
the fingers, palms, or the soles of the feet can last for
years. In teenagers and young adults, atopic dermatitis
often appears on one or more of the following areas:
448

A close-up view of atopic dermatitis in the crook of the
elbow of a 12-year-old patient. (Custom Medical Stock Photo.
Reproduced by permission.)



elbow creases



backs of the knees



ankles



wrists



face



neck



upper chest



palms and between the fingers

Causes and symptoms
While allergic reactions often trigger atopic
dermatitis, the condition is thought to be the result
of an inherited over-active immune system or a
genetic defect that causes the skin to lose abnormally large amounts of moisture. The condition can
GALE ENCYCLOPEDIA OF MEDICINE

Atopic dermatitis

Infant

Adult

Atopic dermatitis can erupt on any part of the skin. In infants, it often appears on the face, scalp, and knees, while it develops on
the elbows, neck, back of the knees, and ankles in adults. (Illustration by Electronic Illustrators Group.)

KEY TERMS
Corticosteroid—A steroid hormone produced by
the adrenal gland or as a synthetic compound that
reduces inflammation, redness, rashes, and irritation.
Dermatitis—Inflammation of the skin.

be aggravated by a cycle that develops in which the
skin itches, the patient scratches, the condition worsens, the itching worsens, the patient scratches, etc.
GALE ENCYCLOPEDIA OF MEDICINE

This cycle must be broken by relieving the itching to
allow the skin time to heal. If the skin becomes
broken, there is also a risk of developing skin infections which, if not recognized and treated promptly,
can become more serious.
Symptoms of atopic dermatitis include the
following:


an itchy rash and dry, thickened skin on areas of the
body where moisture can be trapped



continual scratching



chronic fatigue, caused when itching disrupts sleep
449

Atopic dermatitis

An individual is more at-risk for developing the
condition if there is a personal or family history of
atopic dermatitis, hay fever, asthma, or other allergies.
Exposure to any of the following can cause a flare-up:


hot or cold temperatures



wool and synthetic fabrics



detergents, fabric softeners, and chemicals



use of drugs that suppress immune-system activity

Certain foods, such as peanuts, cow’s milk, eggs,
and fish, can trigger symptoms of atopic dermatitis.
A small percentage of patients with atopic dermatitis
find that their symptoms worsen after having been
exposed to dust, feather pillows, rough-textured fabrics, or other materials to which dust adheres.

Diagnosis
Diagnosis of atopic dermatitis is usually based on
the patient’s symptoms and personal and family
health history. Skin tests do not generally provide
reliable information about this condition.

Treatment
Atopic dermatitis cannot be cured, but the severity and duration of symptoms can be controlled.
A dermatologist should be consulted when symptoms
first appear, and is likely to recommend warm baths to
loosen encrusted skin, followed by applications of
petroleum jelly or vegetable shortening to prevent the
skin’s natural moisture from escaping.
Externally applied (topical) steroids or preparations containing coal tar can relieve minor itching, but
coal tar has an unpleasant odor, stains clothes, and
may increase skin-cancer risk. Excessive use of steroid
creams in young children can alter growth. Pregnant
women should not use products that contain coal tar.
Topical steroids can cause itching, burning, acne, permanent stretch marks, and thinning and spotting of
the skin. Applying topical steroids to the area around
the eyes can cause glaucoma.

who use cortisone salves or lotions to control widespread symptoms. Oral cortisone may be prescribed
if the patient does not respond to other treatments,
but patients who take the medication for more than
two weeks have a greater-than-average risk of developing severe symptoms when the treatment is
discontinued.
Allergy shots rarely improve atopic dermatitis
and sometimes aggravate the symptoms. Since food
allergies may trigger atopic dermatitis, the doctor
may suggest eliminating certain foods from the diet if
other treatments prove ineffective.
If symptoms are extremely severe, ultraviolet
light therapy may be prescribed, and a wet body
wrap recommended to help the skin retain moisture. This technique, used most often with children,
involves sleeping in a warm room while wearing
wet pajamas under dry clothing, rain gear, or a
nylon sweatsuit. The patient’s face may be covered
with wet gauze covered by elastic bandages, and
his hands encased in wet socks covered by dry
ones.
A physician should be notified if the condition is
widespread or resists treatment, or the skin oozes,
becomes encrusted, or smells, as this may indicate an
infection.

Alternative treatment
Alternative therapies can sometimes bring relief
or resolution of atopic dermatitis when conventional
therapies are not helping. If the condition becomes
increasingly widespread or infected, a physician
should be consulted.
Helpful alternative treatments for atopic dermatitis may include:


Taking regular brisk walks, followed by bathing in
warm water sprinkled with essential oil of lavender
(Lavandula officinalis); lavender oil acts as a nerve
relaxant for the whole body including the skin

Oral antihistamines, such as diphenhydramine
(Benadryl), can relieve symptoms of allergy-related
atopic dermatitis. More concentrated topical steroids
are recommended for persistent symptoms. A mild
tranquilizer may be prescribed to reduce stress and
help the patient sleep, and antibiotics are used to
treat secondary infections.



Supplementing the diet daily with zinc, fish oils, vitamin A, vitamin E, and evening primrose oil (Oenothera
biennis)–all good sources of nutrients for the skin



Reducing or eliminating red meat from the diet



Eliminating or rotating potentially allergic foods
such as cow’s milk, peanuts, wheat, eggs, and soy

Cortisone ointments should be used sparingly,
and strong preparations should never be applied
to the face, groin, armpits, or rectal area. Regular
medical monitoring is recommended for patients



Implementing stress reduction techniques in daily
life.

450

Herbal therapies also can be helpful in treating
atopic dermatitis. Western herbal remedies used in the
GALE ENCYCLOPEDIA OF MEDICINE

Other alternative techniques that may be useful in
the treatment of atopic dermatitis include:


Acupressure (acupuncture without needles) to relieve
tension that may trigger a flare



Aromatherapy, using essential oils like lavender,
thyme (Thymus vulgaris), jasmine (Jasminum officinale) and chamomile (Matricaria recutita) in hot
water, to add a soothing fragrance to the air



Shiatsu massage and reflexology, performed by
licensed practitioners, to alleviate symptoms by
restoring the body’s natural balance



Homeopathy, which may temporarily worsen
symptoms before relieving them, and should be
supervised by a trained alternative healthcare
professional



Hydrotherapy, which uses water, ice, liquid, and
steam, to stimulate the immune system



Juice therapy to purify the liver and relieve bowel
congestion





avoid wool, perfumes, fabric softeners, soaps that
dry the skin, and other irritants



avoid sudden temperature changes

A doctor should be notified whenever any of the
following occurs:


fever or relentless itching develop during a flare



an unexplained rash develops in someone who has a
personal or family history of eczema or asthma



inflammation does not decrease after seven days of
treatment with an over-the-counter preparation containing coal tar or steroids



a yellow, tan, or brown crust or pus-filled blisters
appear on top of an existing rash



a person with active atopic dermatitis comes into
contact with someone who has cold sores, genital
herpes, or another viral skin disease

Resources
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham Road,
P.O. Box 4014, Schaumburg, IL 60168-4014. (847) 3300230. Fax: (847) 330-0050. <http://www.aad.org>.

Maureen Haggerty

Yoga to induce a sense of serenity.

Prognosis
Atopic dermatitis is unpredictable. Although
symptoms occur less often with age and sometimes
disappear altogether, they can recur without warning. Atopic dermatitis lowers resistance to infection
and increases the risk of developing cataracts. Sixty
percent of patients with atopic dermatitis will
experience flares and remissions throughout their
lives.

Prevention
Research has shown that babies weaned from
breast milk before they are four months old are almost
three times more likely than other babies to develop
recurrent eczema. Feeding eggs or fish to a baby less
than one year old can activate symptoms, and babies
should be shielded from such irritants as mites, molds,
pet hair, and smoke.
Possible ways to prevent flare-ups include the
following:


eliminate activities that cause sweating



lubricate the skin frequently

GALE ENCYCLOPEDIA OF MEDICINE

I Atrial ectopic beats
Definition
Atrial ectopic beats (AEB) refers to a contraction
of the upper heart chamber which occurs before it
would be expected. Atrial ectopic beats are also
known as premature atrial beats, premature atrial
complex (PAC), or atrial extrasystole.

Description
An AEB is usually a harmless disturbance in the
normal rhythm of the heart. It can occur only occasionally, in a regular pattern, or several may occur in
sequence and then disappear. Most often, the person is
unaware of the event.

Causes and symptoms
As people age, extra beats tend to happen more
frequently even in perfectly healthy individuals. AEB
may be triggered or increased by stress, caffeine, smoking, and some medicines. Cold remedies containing
451

Atrial ectopic beats

treatment of this condition include burdock (Arctium
lappa) and Ruta (Ruta graveolens). Long-term herbal
therapy requires monitoring and should be guided by
an experienced practitioner.

Atrial fibrillation and flutter

ephedrine or pseudoephedrine have been known to
increase the incidence of atrial ectopic beats. AEB
may also be the result of an enlarged atria, lung disease, or the result of reduced blood supply to that area
of the heart.
If a person is aware of the event, the first symptom
of AEB is usually a feeling that the heart has skipped
or missed a beat. This is often accompanied by a
feeling that the heart is thumping or pounding in the
chest. The thumping or pounding is caused by the fact
that when there is an AEB, the pause before the next
beat is usually longer than normal. The next beat must
be stronger than usual to pump the accumulated blood
out of the chamber.

Diagnosis
Diagnosis of AEB is often suspected on the basis of
the patient’s description of the occurrence. An electrocardiogram (ECG) can confirm the diagnosis. An ECG
shows the heart beat as three wave forms. The first wave
is called P, the second is called QRS, and the last is T. An
atrial ectopic beat will show up on the ECG as a P wave
that occurs closer than usual to the preceding T wave.

Treatment
Atrial ectopic beats do not usually require treatment. If treatment is necessary because the beats occur
frequently and cause intolerable discomfort, the doctor may prescribe medication.

Prognosis
Occasional AEB usually have no significance. If
they increase in frequency, they can lead to atrial
tachycardia or fibrillation and to a decrease in cardiac
output.

Prevention
AEB cannot usually be prevented. Aggravating
factors can be addressed, like excessive stimulants,
and uncontrolled pulmonary disorders.

I Atrial fibrillation and flutter
Definition
Atrial fibrillation and flutter are abnormal heart
rhythms in which the atria, or upper chambers of the
heart, are out of sync with the ventricles, or lower
chambers of the heart. In atrial fibrillation, the atria
‘‘quiver’’ chaotically and the ventricles beat irregularly. In atrial flutter, the atria beat regularly and
faster than the ventricles.

Description
Atrial fibrillation and flutter are two types of
cardiac arrhythmias, irregularities in the heart’s
rhythm. Nearly 2 million Americans have atrial fibrillation, according to the American Heart Association.
It is the most common chronic arrhythmia. Atrial
flutter is less common, but both of these arrhythmias
can cause a blood clot to form in the heart. This can
lead to a stroke or a blockage carried by the blood flow
(an embolism) anywhere in the body’s arteries. Atrial
fibrillation is responsible for about 15% of strokes.
The atria are the heart’s two small upper chambers. In atrial fibrillation, the heart beat is completely irregular. The atrial muscles contract very
quickly and irregularly; the ventricles, the heart’s
two large lower chambers, beat irregularly but not
as fast as the atria. When the atria fibrillate, blood
that is not completely pumped out can pool and
form a clot. In atrial flutter, the heart beat is
usually very fast but steady. The atria beat faster
than the ventricles.
Atrial fibrillation often occurs in people with various types of heart disease. Atrial fibrillation may also
result from an inflammation of the heart’s covering
(pericarditis), chest trauma or surgery, pulmonary disease, and certain medications. Atrial fibrillation is
more common in older people; about 10% of people
over the age of 75 have it. Atrial flutter and fibrillation
usually occur in people with hypertensive or coronary
heart disease and other types of heart disorders.

Resources

Causes and symptoms

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dorothy Elinor Stonely

Atrial extrasystole see Atrial ectopic beats
452

In most cases, the cause of atrial fibrillation and
flutter can be found, but often it cannot. Causes of
these heart beat abnormalities include:


many types of heart disease



stress and anxiety



caffeine
GALE ENCYCLOPEDIA OF MEDICINE

Arrhythmia—A variation in the normal rhythm of
the heart beat. Atrial fibrillation and flutter are two
types of arrhythmia.
Atria—The two small upper chambers of the heart
that receive blood from the lungs and the body.
Stroke—A brain attack caused by a sudden disruption of blood flow to the brain, in this case because
of a blood clot.
Ventricles—The two large lower chambers of the
heart that pump blood to the lungs and to the rest of
the body.



alcohol



tobacco



diet pills



some prescription and over-the-counter medications



open heart surgery
Symptoms, when present, include:



a fluttering feeling in the chest



a pulse that feels like the heart is skipping, racing,
jumping, or is irregular



low energy



a faint or dizzy feeling



pressure or discomfort in the chest



shortness of breath



anxiety

Diagnosis
A doctor can sometimes hear these arrhythmias
using an instrument (a stethoscope) to listen to the
sounds within the chest. Atrial fibrillation and flutter
are usually diagnosed through electrocardiography
(EKGs), an exercise stress test, a 24-hour Holter
EKG monitor, or a telephone cardiac monitor. An
EKG shows the heart’s activity and may reveal a
lack of oxygen (ischemia). Electrodes covered with
conducting jelly are placed on the patient’s chest,
arms, and legs. The electrodes send impulses of the
heart’s activity through a monitor (called an oscilloscope) to a recorder that traces the pattern of the
impulses onto paper. The test takes about 10 minutes
and is performed in a doctor’s office. The exercise
stress test measures how the heart and blood vessels
GALE ENCYCLOPEDIA OF MEDICINE

respond to work when the patient is exercising on a
treadmill or a stationary bike. This test is performed in
a doctor’s office within an exercise laboratory and
takes 15-30 minutes.
In 24-hour EKG (Holter) monitoring, the
patient wears a small, portable tape recorder connected to disks on his/her chest that record the
heart’s rhythm during normal activities. An EKG
called transtelephonic monitoring identifies arrhythmias that occur infrequently. Like Holter monitoring, transtelephonic monitoring continues for days
or weeks and enables patients to send the EKG via
telephone to a monitoring station when an arrhythmia
is felt, or to store the information in the recorder and
transmit it later. Doctors can also use high-frequency
sound waves (echocardiography) to determine the
structure and function of the heart. This diagnostic
method is often helpful to evaluate for underlying
heart disease.

Treatment
Atrial fibrillation and flutter are usually treated
with medications and/or electrical shock (cardioversion). In some cases, removal of a small portion of the
heart (ablation), implantation of a pacemaker or a
cardioverter defibrillator, or maze surgery is needed.
If the heart rate cannot be quickly controlled,
electrical cardioversion may be used. Cardioversion,
the electric shock to the chest wall, is usually performed emergencies. This device briefly suspends the
heart’s activity and allows it to return to a normal
rhythm.
Ablation destroys the heart tissue that causes the
arrhythmia. The tissue can be destroyed by catheterization or surgery. Radiofrequency catheter ablation,
performed in a cardiac catheterization laboratory, can
cure atrial flutter and control the heart rate in atrial
fibrillation. The patient is awake but sedated. A thin
tube called a catheter is inserted into a vein and is
threaded into the heart. At the end of the catheter, a
device maps the electrical pathways of the heart. A
cardiologist, a doctor specializing in the heart, uses
this map to identify the pathway(s) causing the
arrhythmia, and then eliminates it (them) with bursts
of high-frequency radio waves. Surgical ablation is
performed in an operating room under general
anesthesia. Computerized mapping techniques are
combined with a cold probe to destroy arrhythmiacausing tissue. Ablation is generally successful. When
ablation is used for atrial fibrillation, it is usually
followed by implantation of a pacemaker as well as
drug therapy.
453

Atrial fibrillation and flutter

KEY TERMS

Atrial septal defect

A pacemaker is a battery-powered device about the
size of a matchbox that is surgically implanted near the
collarbone to regulate the heart beat. Lead wires
threaded to the right side of the heart supply electrical
energy to pace the atria and ventricles. The implantable
cardioverter defibrillator is a treatment for serious
arrhythmias. The battery-powered device senses an
abnormal heart rhythm and automatically provides electrical shock(s). The shock(s) suspends heart activity and
then allows the heart to initiate a normal rhythm. Wire
electrodes on the device are attached to the heart. Some
of the electrodes are attached to the outside of the heart
and some are attached to the inside of the heart through
veins. The newest implantable cardioverter defibrillators
can be implanted in the chest wall and do not require
open chest surgery. These devices weigh less than 10 oz
and generally last seven or eight years. An implantable
cardioverter defibrillator is usually used with drug therapy, but the amount medication is reduced. In maze
surgery, often the last resort, surgeons create a maze of
stitches (sutures) that help the heart’s electrical impulses
travel effectively.
Most of the drugs used for treatment have potential side effects and should be carefully monitored by a
doctor. The goal of treatment is to control the rate and
rhythm of the heart and to prevent the formation of
blood clots. If the arrhythmia is caused by heart disease, the heart disease will also be treated. The
American Heart Association recommends aggressive
treatment.
A digitalis drug, most commonly digoxin, is
usually prescribed to control the heart rate. Digitalis
drugs slow the heart’s electrical impulses, helping to
restore the normal rate and rhythm. These drugs also
increase the ability of the heart’s muscular layer to
contract and pump properly. Beta-blockers and
calcium channel blockers can also be used for this
purpose. Beta-blockers slow the speed of electrical
impulses through the heart. Some calcium channel
blockers dampen the heart’s response to erratic electrical impulses.
To prevent blood clots, aspirin or warfarin
(Coumadin) is administered. Warfarin, however, has
potential bleeding side effects, especially in older
patients. Amiodarone is fairly efffective for atrial flutter. This drug is often able to maintain the heart’s
proper rhythm and can also help control the heart
rate when the flutter occurs.

Prognosis
Patients with atrial fibrillation and flutter can
live a normal life for many years as long as the
454

arrhythmia is controlled and serious blood clots
are prevented.

Prevention
Atrial fibrillation and flutter can sometimes be
prevented when the cause can be identified and controlled. Depending on the cause, prevention could
include:


treating the underlying heart disease



reducing stress and anxiety



reducing or stopping consumption of caffeine, alcohol, or tobacco; and/or



discontinuing diet pills or other medications (overthe-counter or prescription)

Resources
PERIODICALS

Kosinski, Daniel, et al. ‘‘Catheter Ablation for Atrial Flutter
and Fibrillation: An Effective Alternative to Medical
Therapy.’’ Postgraduate Medicine103, no. 1 (January
1998): 103-110.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto

Atrial flutter see Atrial fibrillation and flutter

I Atrial septal defect
Definition
An atrial septal defect is an abnormal opening in
the wall separating the left and right upper chambers
(atria) of the heart.

Description
During the normal development of the fetal
heart, there is an opening in the wall (the septum)
separating the left and right upper chambers of the
heart. Normally, this opening closes before birth,
GALE ENCYCLOPEDIA OF MEDICINE

Different types of atrial septal defects can
occur, and they are classified according to where
in the separating wall they are found. The most
commonly found atrial septal defect occurs in the
middle of the atrial septum and accounts for about
70% of all atrial septal defects. Abnormal openings
can form in the upper and lower parts of the atrial
septum as well.

Causes and symptoms
Abnormal openings in the atrial septum occur
during fetal development and are twice as common
in females as in males. These abnormalities can go
unnoticed if the opening is small, producing no
abnormal symptoms. If the defect is big, large
amounts of blood flowing from the left to the
right atrium will cause the right atrium to swell to
hold the extra blood.
People born with an atrial septal defect can have
no symptoms through their twenties, but by age 40,
most people with this condition have symptoms that
can include shortness of breath, rapid abnormal beating of the atria (atrial fibrillation), and eventually
heart failure.

Diagnosis
Atrial septal defects can be identified by various
methods. Abnormal changes in the sound of the
heart beats can be heard when a doctor listens to
the heart with a stethoscope. In addition, a chest
x ray, an electrocardiogram (ECG, an electrical
printout of the heartbeats), and an echocardiogram
(a test that uses sound waves to form a detailed
image of the heart) can also be used to identify
this condition.
An atrial septal defect can also be diagnosed by
using a test called cardiac catheterization. This test
involves inserting a very thin tube (catheter) into the
heart’s chambers to measure the amount of oxygen
present in the blood within the heart. If the heart
has an opening between the atria, oxygen-rich blood
from the left atrium enters the right atrium.
Through cardiac catheterization, doctors can detect
the higher-than-normal amount of oxygen in the
heart’s right atrium, right ventricle, and the large
blood vessels that carry blood to the lungs, where
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cardiac catheterization—A test that involves having a tiny tube inserted into the heart through a
blood vessel.
Dacron—A synthetic polyester fiber used to surgically repair damaged sections of heart muscle and
blood vessel walls.
Echocardiogram—A test that uses sound waves to
generate an image of the heart, its valves, and
chambers.

the blood would normally subsequently get its
oxygen.

Treatment
Atrial septal defects often correct themselves without medical treatments by the age of two. If this dose
not happen, surgery is done by sewing the hole closed,
or by sewing a patch of Dacron material or a piece of
the sac that surrounds the heart (the pericardium),
over the opening.
Some patients can have the defect fixed by having
an clam-shaped plug placed over the opening. This
plug is a man-made device that is put in place through
a catheter inserted into the heart.

Prognosis
Individuals with small defects can live a normal
life, but larger defects require surgical correction. Less
than 1% of people younger than 45 years of age die
from corrective surgery. Five to ten percent of patients
can die from the surgery if they are older than 40 and
have other heart-related problems. When an atrial
septal defect is corrected within the first 20 years of
life, there is an excellent chance for the individual to
live normally.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dominic De Bellis, PhD

Atrioventricular block see Heart block
Attapulgite see Antidiarrheal drugs
455

Atrial septal defect

but if it does not, the child is born with a hole
between the left and right atria. This abnormal
opening is called an atrial septal defect and causes
blood from the left atrium to flow into the right
atrium.

Attention-deficit/Hyperactivity disorder (ADHD)

I

Attention-deficit/
Hyperactivity disorder
(ADHD)

Definition
Attention-deficit/hyperactivity disorder (ADHD)
is a developmental disorder characterized by distractibility, hyperactivity, impulsive behaviors, and the
inability to remain focused on tasks or activities.

Drugs Used To Treat ADHD

Brand Name (Generic Name)

Possible Common Side Effects
Include:

Cylert (pemoline)
Dexedrine (dextroamphetamine
sulfate)
Ritalin (methylphenidate
hydrochloride)

Insomnia
Excessive stimulation, restlessness
Insomnia, nervousness, loss of
appetite

Description
ADHD, also known as hyperkinetic disorder
(HKD) outside of the United States, is estimated to
affect 3-9% of children, and afflicts boys more often
than girls. Although difficult to assess in infancy and
toddlerhood, signs of ADHD may begin to appear as
early as age two or three, but the symptom picture
changes as adolescence approaches. Many symptoms,
particularly hyperactivity, diminish in early adulthood, but impulsivity and inattention problems
remain with up to 50% of ADHD individuals
throughout their adult life.
Children with ADHD have short attention
spans, becoming easily bored and/or frustrated
with tasks. Although they may be quite intelligent,
their lack of focus frequently results in poor grades
and difficulties in school. ADHD children act
impulsively, taking action first and thinking later.
They are constantly moving, running, climbing,
squirming, and fidgeting, but often have trouble
with gross and fine motor skills and, as a result,
may be physically clumsy and awkward. Their
clumsiness may extend to the social arena, where
they are sometimes shunned due to their impulsive
and intrusive behavior.

Causes and symptoms
The causes of ADHD are not known. However,
it appears that heredity plays a major role in the
development of ADHD. Children with an ADHD
parent or sibling are more likely to develop the
disorder themselves. In 2004, scientists reported at
least 20 candidate genes that might contribute to
ADHD, but no single gene stood out as the gene
causing the condition. Before birth, ADHD children
may have been exposed to poor maternal nutrition,
viral infections, or maternal substance abuse. In
early childhood, exposure to lead or other toxins
can cause ADHD-like symptoms. Traumatic brain
injury or neurological disorders may also trigger
456

KEY TERMS
Conduct disorder—A behavioral and emotional
disorder of childhood and adolescence. Children
with a conduct disorder act inappropriately,
infringe on the rights of others, and violate societal
norms.
Nervous tic—A repetitive, involuntary action, such
as the twitching of a muscle or repeated blinking.
Oppositional defiant disorder—A disorder characterized by hostile, deliberately argumentative, and
defiant behavior toward authority figures.

ADHD symptoms. Although the exact cause of
ADHD is not known, an imbalance of certain neurotransmitters, the chemicals in the brain that transmit messages between nerve cells, is believed to be
the mechanism behind ADHD symptoms.
A widely publicized study conducted by Dr. Ben
Feingold in the early 1970s suggested that allergies to
certain foods and food additives caused the characteristic hyperactivity of ADHD children. Although some
children may have adverse reactions to certain foods
that can affect their behavior (for example, a rash
might temporarily cause a child to be distracted from
other tasks), carefully controlled follow-up studies
have uncovered no link between food allergies and
ADHD. Another popularly held misconception
about food and ADHD is that the consumption of
sugar causes hyperactive behavior. Again, studies
have shown no link between sugar intake and
ADHD. It is important to note, however, that a nutritionally balanced diet is important for normal development in all children.
Psychologists and other mental health professionals typically use the criteria listed in the Diagnostic
and Statistical Manual of Mental Disorders, Fourth
GALE ENCYCLOPEDIA OF MEDICINE

Inattention:


fails to pay close attention to detail or makes careless
mistakes in schoolwork or other activities



has difficulty sustaining attention in tasks or
activities



does not appear to listen when spoken to



does not follow through on instructions and does not
finish tasks



has difficulty organizing tasks and activities



avoids or dislikes tasks that require sustained mental
effort (e.g., homework)



is easily distracted



is forgetful in daily activities
Hyperactivity:



fidgets with hands or feet or squirms in seat



does not remain seated when expected to



runs or climbs excessively when inappropriate (in
adolescents and adults, feelings of restlessness)



has difficulty playing quietly



is constantly on the move



talks excessively
Impulsivity:



blurts out answers before the question has been
completed



has difficulty waiting for his or her turn



interrupts and/or intrudes on others

Diagnosis
The first step in determining if a child has ADHD
is to consult with a pediatrician. The pediatrician can
make an initial evaluation of the child’s developmental
maturity compared to other children in his or her age
group. The physician should also perform a comprehensive physical examination to rule out any organic
causes of ADHD symptoms, such as an overactive
thyroid or vision or hearing problems.
If no organic problem can be found, a psychologist, psychiatrist, neurologist, neuropsychologist, or
learning specialist is typically consulted to perform a
comprehensive ADHD assessment. A complete medical, family, social, psychiatric, and educational history
GALE ENCYCLOPEDIA OF MEDICINE

is compiled from existing medical and school records
and from interviews with parents and teachers.
Interviews may also be conducted with the child,
depending on his or her age. Along with these interviews, several clinical inventories may also be used,
such as the Conners Rating Scales (Teacher’s
Questionnaire and Parent’s Questionnaire), Child
Behavior Checklist (CBCL), and the Achenbach
Child Behavior Rating Scales. These inventories provide valuable information on the child’s behavior in
different settings and situations. In addition, the
Wender Utah Rating Scale has been adapted for use
in diagnosing ADHD in adults.
It is important to note that mental disorders such
as depression and anxiety disorder can cause symptoms similar to ADHD. A complete and comprehensive psychiatric assessment is critical to differentiate
ADHD from other possible mood and behavioral disorders. Bipolar disorder, for example, may be misdiagnosed as ADHD.
Public schools are required by federal law to offer
free ADHD testing upon request. A pediatrician can
also provide a referral to a psychologist or pediatric
specialist for ADHD assessment. Parents should
check with their insurance plans to see if these services
are covered.

Treatment
Psychosocial therapy, usually combined with
medications, is the treatment approach of choice to
alleviate ADHD symptoms. Psychostimulants, such
as dextroamphetamine (Dexedrine), pemoline
(Cylert), and methylphenidate (Ritalin) are commonly
prescribed to control hyperactive and impulsive behavior and increase attention span. They work by stimulating the production of certain neurotransmitters in
the brain. Possible side effects of stimulants include
nervous tics, irregular heartbeat, loss of appetite, and
insomnia. However, the medications are usually welltolerated and safe in most cases. In 2004, longer-acting
stimulants had been released to treat adult ADHD.
In 2004, the American Academy of Child and
Adolescent Psychiatry listed the first nonstimulant as a
first-line therapy for ADHD. Called atomoxetine HCI
(Strattera), it is a norepinephrine reuptake inhibitor.
In children who do not respond well to stimulant
therapy, tricyclic antidepressants such as desipramine
(Norpramin, Pertofane) and amitriptyline (Elavil) are
sometimes recommended. Reported side effects of
these drugs include persistent dry mouth, sedation,
disorientation, and cardiac arrhythmia (particularly
457

Attention-deficit/Hyperactivity disorder (ADHD)

Edition (DSM-IV) as a guideline for determining the
presence of ADHD. For a diagnosis of ADHD, DSMIV requires the presence of at least six of the following
symptoms of inattention, or six or more symptoms of
hyperactivity and impulsivity combined:

Attention-deficit/Hyperactivity disorder (ADHD)

with desipramine). Other medications prescribed for
ADHD therapy include buproprion (Wellbutrin), an
antidepressant; fluoxetine (Prozac), an SSRI antidepressant; and carbamazepine (Tegretol, Atretol), an
anticonvulsant drug. Clonidine (Catapres), an antihypertensive medication, has also been used to control
aggression and hyperactivity in some ADHD children,
although it should not be used with Ritalin. A child’s
response to medication will change with age and
maturation, so ADHD symptoms should be monitored closely and prescriptions adjusted accordingly.
Behavior modification therapy uses a reward system to reinforce good behavior and task completion
and can be implemented both in the classroom and at
home. A tangible reward such as a sticker may be
given to the child every time he completes a task or
behaves in an acceptable manner. A chart system may
be used to display the stickers and visually illustrate
the child’s progress. When a certain number of stickers
are collected, the child may trade them in for a bigger
reward such as a trip to the zoo or a day at the beach.
The reward system stays in place until the good behavior becomes ingrained.
A variation of this technique, cognitive-behavioral
therapy, works to decrease impulsive behavior by getting the child to recognize the connection between
thoughts and behavior, and to change behavior by
changing negative thinking patterns.
Individual psychotherapy can help an ADHD
child build self-esteem, give them a place to discuss
their worries and anxieties, and help them gain insight
into their behavior and feelings. Family therapy may
also be beneficial in helping family members develop
coping skills and in working through feelings of guilt
or anger parents may be experiencing.
ADHD children perform better within a familiar,
consistent, and structured routine with positive reinforcements for good behavior and real consequences
for bad. Family, friends, and caretakers should all be
educated on the special needs and behaviors of the
ADHD child. Communication between parents and
teachers is especially critical to ensuring an ADHD
child has an appropriate learning environment.

Alternative treatment
A number of alternative treatments exist for
ADHD. Although there is a lack of controlled studies
to prove their efficacy, proponents report that they are
successful in controlling symptoms in some ADHD
patients. Some of the more popular alternative treatments include:
458



EEG (electroencephalograph) biofeedback. By measuring brainwave activity and teaching the ADHD
patient which type of brainwave is associated with
attention, EEG biofeedback attempts to train
patients to generate the desired brainwave activity.



Dietary therapy. Based in part on the Feingold food
allergy diet, dietary therapy focuses on a nutritional
plan that is high in protein and complex carbohydrates and free of white sugar and salicylate-containing foods such as strawberries, tomatoes, and grapes.



Herbal therapy. Herbal therapy uses a variety of
natural remedies to address the symptoms of
ADHD, such as ginkgo (Gingko biloba) for memory
and mental sharpness and chamomile (Matricaria
recutita) extract for calming. The safety of herbal
remedies has not been demonstrated in controlled
studies. For example, it is known that gingko may
affect blood coagulation, but controlled studies have
not yet evaluated the risk of the effect.



Homeopathic medicine. The theory of homeopathic
medicine is to treat the whole person at a core level.
Constitutional homeopathic care requires consulting
with a well-trained homeopath who has experience
working with ADD and ADHD individuals.

Prognosis
Untreated, ADHD negatively affects a child’s
social and educational performance and can seriously
damage his or her sense of self-esteem. ADHD children have impaired relationships with their peers, and
may be looked upon as social outcasts. They may be
perceived as slow learners or troublemakers in the
classroom. Siblings and even parents may develop
resentful feelings towards the ADHD child.
Some ADHD children also develop a conduct
disorder problem. For those adolescents who have
both ADHD and a conduct disorder, as many as 25%
go on to develop antisocial personality disorder and
the criminal behavior, substance abuse, and high rate
of suicide attempts that are symptomatic of it.
Children diagnosed with ADHD are also more likely
to have a learning disorder, a mood disorder such as
depression, or an anxiety disorder.
Approximately 70-80% of ADHD patients treated with stimulant medication experience significant
relief from symptoms, at least in the short-term.
Approximately one-half of ADHD children seem to
‘‘outgrow’’ the disorder in adolescence or early adulthood; the other half will retain some or all symptoms
of ADHD as adults. With early identification and
intervention, careful compliance with a treatment
GALE ENCYCLOPEDIA OF MEDICINE

Audiometry

program, and a supportive and nurturing home and
school environment, ADHD children can flourish
socially and academically.
Resources
PERIODICALS

‘‘AACAP Guidelines Include Strattera as a First-line ADHD
Therapy Option.’’ Drug Week (May 28, 2004): 54.
‘‘More Long-acting Stimulants to Treat Adult ADHD.’’
SCRIP World Pharmaceutical News (May 14, 2004): 10123.
‘‘Study Updates Genetics of ADHD.’’ Drug Week (May 21,
2004): 55.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry.
(AACAP). 3615 Wisconsin Ave. NW, Washington, DC
20016. (202) 966-7300. <http://www.aacap.org>.
Children and Adults with Attention Deficit Disorder
(CH.A.D.D.). 8181 Professional Place, Suite 201.
National Attention Deficit Disorder Association. (ADDA).
9930 Johnnycake Ridge Road, Suite 3E, Mentor, OH
44060. (800) 487-2282. <http://www.add.org>.

Paula Anne Ford-Martin
Teresa G. Odle

Attention deficit disorder see Attention-deficit/Hyperactivity disorder (ADHD)
Atypical mycobacterial infections see
Mycobacterial infections, atypical
Atypical pneumonia see Mycoplasma
infections

I Audiometry
Definition
Audiometry is the testing of a person’s ability to
hear various sound frequencies. The test is performed
with the use of electronic equipment called an audiometer. This testing is usually administered by a trained
technician called an audiologist.

Purpose
Audiometry testing is used to identify and diagnose hearing loss. The equipment is used in health
screening programs, for example in grade schools, to
detect hearing problems in children. It is also used in
the doctor’s office or hospital audiology department
to diagnose hearing problems in children, adults, and
GALE ENCYCLOPEDIA OF MEDICINE

An audiologist conducting a hearing test. (Custom Medical
Stock Photo. Reproduced by permission.)

the elderly. With correct diagnosis of a person’s specific pattern of hearing impairment, the right type of
therapy, which might include hearing aids, corrective
surgery, or speech therapy, can be prescribed.

Precautions
Testing with audiometry equipment is simple and
painless. No special precautions are required.

Description
A trained audiologist (a specialist in detecting
hearing loss) uses an audiometer to conduct audiometry testing. This equipment emits sounds or tones, like
musical notes, at various frequencies, or pitches, and
at differing volumes or levels of loudness. Testing is
usually done in a soundproof testing room.
The person being tested wears a set of headphones that blocks out other distracting sounds and
delivers a test tone to one ear at a time. At the sound
of a tone, the patient holds up a hand or finger to
indicate that the sound is detected. The audiologist
lowers the volume and repeats the sound until the
patient can no longer detect it. This process is
repeated over a wide range of tones or frequencies
from very deep, low sounds, like the lowest note
played on a tuba, to very high sounds, like the
pinging of a triangle. Each ear is tested separately.
It is not unusual for levels of sensitivity to sound to
differ from one ear to the other.
A second type of audiometry testing uses a headband rather than headphones. The headband is worn
with small plastic rectangles that fit behind the ears to
459

Auditory integration training

KEY TERMS
Audiogram—A chart or graph of the results of a hearing test conducted with audiographic equipment. The
chart reflects the softest (lowest volume) sounds that
can be heard at various frequencies or pitches.
Decibel—A unit of measure for expressing the
loudness of a sound. Normal speech is typically
spoken in the range of about 20-50 decibels.
Otoscope—A hand-held instrument with a tiny
light and a funnel-shaped attachment called an
ear speculum, which is used to examine the ear
canal and eardrum.

conduct sound through the bones of the skull. The
patient being tested senses the tones that are transmitted as vibrations through the bones to the inner
ear. As with the headphones, the tones are repeated at
various frequencies and volumes.
The results of the audiometry test may be recorded
on a grid or graph called an audiogram. This graph is
generally set up with low frequencies or tones at one end
and high ones at the other end, much like a piano keyboard. Low notes are graphed on the left and high notes
on the right. The graph also charts the volume of the
tones used; from soft, quiet sounds at the top of the
chart to loud sounds at the bottom. Hearing is measured in units called decibels. Most of the sounds associated with normal speech patterns are generally spoken
in the range of 20-50 decibels. An adult with normal
hearing can detect tones between 0-20 decibels.
Speech audiometry is another type of testing that
uses a series of simple recorded words spoken at various volumes into headphones worn by the patient
being tested. The patient repeats each word back to
the audiologist as it is heard. An adult with normal
hearing will be able to recognize and repeat 90-100%
of the words.

Preparation
The ears may be examined with an otoscope prior
to audiometry testing to determine if there are any
blockages in the ear canal due to ear wax or other
material.

Normal results
A person with normal hearing will be able to
recognize and respond to all of the tone frequencies
460

administered at various volumes in both ears by the
audiometry test. An adult with normal hearing can
detect a range of low and high pitched sounds that
are played as softly as between nearly 0-20 decibels.
Normal speech is generally spoken in the range of
20-50 decibels.

Abnormal results
Audiometry test results are considered abnormal
if there is a significant or unexplained difference
between the levels of sound heard between the two
ears, or if the person being tested is unable to hear in
the normal range of frequencies and volume. The
pattern of responses displayed on the audiogram can
be used by the audiologist to identify if a significant
hearing loss is present and if the patient might benefit
from hearing aids or corrective surgery.
Resources
ORGANIZATIONS

American Academy of Audiology. 8201 Greensboro Drive,
Suite 300, McLean, VA 22102. (703) 610-9022. <http://
audiology.org>.
Audiology Awareness Campaign. 3008 Millwood Ave.,
Columbia, SC 29205. (800) 445-8629.
OTHER

‘‘How to Read Your Hearing Test.’’ Hearing Alliance
ofAmerica. <http://www.earinfo.com>.
‘‘Understanding Your Audiogram.’’ The League for the
Hard of Hearing. <http://www.lhh.org>.

Altha Roberts Edgren

I Auditory integration training
Definition
Auditory integration training, or AIT, is one specific type of music/auditory therapy based upon the
work of French otolaryngologists Dr. Alfred Tomatis
and Dr. Guy Berard.

Origins
The premise upon which most auditory integration programs are based is that distortion in how
things are heard contributes to commonly seen
behavioral or learning disorders in children. Some
of these disorders include attention deficit/hyperactive disorder (ADHD), autism, dyslexia, and central
GALE ENCYCLOPEDIA OF MEDICINE

parents’ fellow opera singers. From these experiences with
the sound of music, he developed the principle that has
come to be known as the Tomatis Effect, i.e. that the human
voice can only sing what it hears.
Tomatis has been called the Einstein of the ear. It was
his research that made the world aware that the ears of an
infant in utero are already functioning at four and half
months of age. Just as the umbilical cord provides nourishment to the unborn infant’s body, Tomatis postulated that
the sound of the mother’s voice is also a nutrient heard by
the fetus. This sound literally charges and stimulates the
growth of the brain.

(Photograph by V. Brynner. Gamma Liaison. Reproduced by
permission.)

Internationally renowned French otolaryngologist,
psychologist, educator and inventor Alfred Tomatis perceived the importance of sound and hearing early in
his career. He took his degree as a Doctor of Medicine
from the University of Paris and specialized in ear,
nose and throat medicine. The son of two opera singers, Tomatis early in his career treated some of his

auditory processing disorders (CAPD). Training the
patient to listen can stimulate central and cortical
organization.
Auditory integration is one facet of what audiologists call central auditory processing. The simplest
definition of central auditory processing, or CAP, is
University of Buffalo Professor of Audiology Jack
Katz’s, which is: ‘‘What we do with what we hear.’’
Central auditory integration is actually the perception
of sound, including the ability to attend to sound, to
remember it, retaining it in both the long- and shortterm memory, to be able to listen to sound selectively,
and to localize it.
Guy Berard developed one of the programs commonly used. Berard’s auditory integration training
consists of twenty half-hour sessions spent listening
to musical sounds via a stereophonic system. The
music is random, with filtered frequencies, and the
person listens through earphones. These sound waves
GALE ENCYCLOPEDIA OF MEDICINE

Tomatis took this further, into the realm of language.
Tomatis concluded that the need to communicate and to
be understood are among our most basic needs. He was a
pioneer in perceiving that language problems convert into
social problems for people. ‘‘Language is what characterizes man and makes him different from other creatures,’’
Tomatis is quoted as saying. The techniques he developed
to teach people how to listen effectively are internationally
respected tools used in the treatment of autism, attentiondeficit disorder, and other learning disabilities.
His listening program, the invention of the Electronic
Ear, and his work with the therapeutic use of sound and
music for the past fifty years have made Tomatis arguably
the best known and most successful ear specialist in the
world. There are more than two hundred Tomatis Centers
worldwide, treating a vast variety of problems related to
the ability to hear.

vibrate and exercise structures in the middle ear. This
is normally done in sessions twice a day for 10 days.
Alfred Tomatis is also the inventor of the
Electronic Ear. This device operates through a series
of filters, and reestablishes the dominance of the right
ear in hearing. The basis of Tomatis’ work is a series of
principles that follow:


The most important purpose of the ear is to adapt
sound waves into signals that charge the brain.



Sound is conducted via both air and bone. It can be
considered something that nourishes the nervous
system, either stimulating or destimulating it.



Just as seeing is not the same as looking, hearing is not
the same as listening. Hearing is passive. Listening is
active.



A person’s ability to listen affects all language development for that person. This process influences every
aspect of self-image and social development.
461

Auditory integration training

A L F R E D T O M A T I S (1920– )

Auditory integration training



The capacity to listen can be changed or improved
through auditory stimulation using musical and
vocal sounds at high frequencies.



Communication begins in the womb. As early as the
beginning of the second trimester, fetuses can hear
sounds. These sounds literally cause the brain and
nervous system of the baby to develop.

Description
A quartet of CAP defects have been identified that
can unfavorably alter how each person processes
sound. Among these are:


Phonetic decoding, a problem that occurs when the
brain incorrectly decodes what is being heard.
Sounds are unrecognizable, often because the person
speaking talks too fast.



Tolerance-fading memory, a condition with little or
poor tolerance for background sounds.



Auditory integration involves a person’s ability to
put together things heard with things seen.
Characteristically there are long response delays
and trouble with phonics, or recognizing the symbols
for sounds.



The fourth problem area, often called auditory organization, overlaps the previous three. It is characterized by disorganization in handling auditory and
other information.

Certain audiological tests are carried out to see if
the person has a CAP problem, and if so, how severe it
is. Other tests give more specific information regarding the nature of the CAP problem. They include:


Puretone air-conduction threshold testing, which measures peripheral hearing loss. If loss is found, then
bone-conduction testing, or evaluation of the vibration of small bones in the inner ear, is also carried out.



Word discrimination scores (WDS) determines a person’s clarity in hearing ideal speech. This is done by
presenting 25–50 words at 40 decibels above the
person’s average sound threshold in each ear. Test
scores equal the percentage of words heard correctly.



Immittance testing is made up of two parts, assessing
the status of, and the protective mechanisms of the
middle ear.



Staggered sporadic word (SSW) testing delivers 40
compound words in an overlapping way at 50 decibels above threshold to each ear of the person being
tested. This test provides expanded information that
makes it possible to break down CAP problems into
the four basic types.

462



Speech in noise discrimination (SN) testing is similar
to Staggered Sporadic Word testing except that other
noise is also added and the percentage correct in
quiet is compared with that correct when there is
added noise.



Phonemic synthesis (PS) determines serious learning
problems. The types of errors made in sounding out
written words or associating written letters with the
sounds they represent help in determining the type
and severity of CAP problems.

Purpose
Upon completion of an auditory integration
training program, the person’s hearing should be capable of perceiving all frequencies at, or near, the same
level. Total improvement from this therapy, in both
hearing and behavior, can take up to one year.

Research and general acceptance
Auditory integration training is based upon newly
learned information about the brain. Though brain
structures and connections are predetermined, probably by heredity, another factor called plasticity also
comes into play. Learning, we now know, continues
from birth to death. Plasticity is the ability of the brain
to actually change its structuring and connections
through the process of learning.
Problems with auditory processing are now
viewed as having a wide–reaching ripple effect on our
society. It is estimated that 30–40% of children starting school have language-learning skills that can be
described as poor. CAP difficulties are a factor in
several different learning disabilities. They affect not
only academic success, but also nearly every aspect of
societal difficulties. One example to illustrate this is a
1989 University of Buffalo study where CAP problems
were found to be present in a surprising 97% of youth
inmates in an upstate New York corrections facility.
Resources
OTHER

Cooper, Rachel. ‘‘What is Auditory Integration Training?’’
December 2000. <http://www.vision3d.com/adhd>.
Dejean, Valerie. About the Tomatis Method, 1997. Tomatis
Auditory Training Spectrum Center, Bethseda, MD.
The Spectrum Center. ‘‘Auditory Integration and
AlfredTomatis.’’ December 2000. <http://
listeningtraining.com>.

Joan Schonbeck

Australia antigen-associated hepatitis see
Hepatitis B
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Autism is a severe disorder of brain function
marked by problems with social contact, intelligence
and language, together with ritualistic or compulsive
behavior and bizarre responses to the environment.

Description
Autism is a lifelong disorder that interferes with
the ability to understand what is seen, heard, and
touched. This can cause profound problems in personal behavior and in the ability to relate to others. A
person with autism must learn how to communicate
normally and how to relate to people, objects and
events. However, not all patients suffer the same
degree of impairment. There is a full spectrum of
symptoms, which can range from mild to severe.
Autism occurs in as many as one or two per 1,000
children. It is found four times more often in boys
(usually the first-born) and occurs around the world
in all races and social backgrounds. Autism usually is
evident in the first three years of life, although in some
children it’s hard to tell when the problem develops.
Sometimes the condition isn’t diagnosed until the
child enters school.
While a person with autism can have symptoms
ranging from mild to severe, about 10% have an
extraordinary ability in one area, such as in mathematics, memory, music, or art. Such children are
known as ‘‘autistic savants’’ (formerly known as
‘‘idiot savants.’’).

Causes and symptoms
Autism is a brain disorder that affects the way the
brain uses or transmits information. Studies have
found abnormalities in several parts of the brain that
almost certainly occurred during fetal development.
The problem may be centered in the parts of the
brain responsible for processing language and information from the senses.
There appears to be a strong genetic basis for
autism. Identical twins are more likely to both be
affected than twins who are fraternal (not genetically
identical). In a family with one autistic child, the
chance of having another child with autism is about
1 in 20, much higher than in the normal population.
Sometimes, relatives of an autistic child have mild
behaviors that look very much like autism, such as
repetitive behaviors and social or communication
GALE ENCYCLOPEDIA OF MEDICINE

At least one group of researchers has found a link
between an abnormal gene and autism. The gene may
be just one of at least three to five genes that interact in
some way to cause the condition. Scientists suspect
that a faulty gene or genes might make a person vulnerable to develop autism in the presence of other
factors, such as a chemical imbalance, viruses or chemicals, or a lack of oxygen at birth.
In a few cases, autistic behavior is caused by a
disease such as:


rubella in the pregnant mother



tuberous sclerosis



fragile X syndrome



encephalitis



untreated phenylketonuria

The severity of the condition varies between individuals, ranging from the most severe (extremely unusual, repetitive, self- injurious, and aggressive
behavior) to very mild, resembling a personality disorder with some learning disability.
Profound problems with social interaction are the
most common symptoms of autism. Infants with the
disorder won’t cuddle; they avoid eye contact and
don’t seem to want or need physical contact or affection. They may become rigid or flaccid when they are
held, cry when picked up, and show little interest in
human contact. Such a child doesn’t smile or lift his
arms in anticipation of being picked up. He forms no
attachment to parents nor shows any normal anxiety
toward strangers. He doesn’t learn typical games of
childhood, such as peek-a-boo.
Language problems
The child with autism may not speak at all; if he
does, it is often in single words. He may endlessly
repeat words or phrases that are addressed to him
and may reverse pronouns (‘‘You go sleep’’ instead
of ‘‘I want to go to sleep’’).
Restricted interests and activity
Usually a child with autism has many problems
playing normally. He probably won’t act out adultroles
during play time, and instead of enjoying fantasy play,
he may simply repeatedly mimic the actions of someone
else. Bizarre behavior patterns are very common among
autistic children and may include complex rituals,
screaming fits, rhythmic rocking, arm flapping, finger
463

Autism

I Autism

problems. Research also has found that some emotional disorders (such as manic depression) occur
more often in families of a child with autism.

Autism
This autistic child is encouraged to interact with the guinea pig in an effort to improve his social interaction. (Helen B. Senisi.
Photo Researchers, Inc. Reproduced by permission.)

twiddling, and crying without tears. Autistic children
may play with their own saliva, feces or urine.They
may be self-destructive, biting their own hands, gouging
at their eyes, pulling their hair, or banging their head.
Sensory problems
The sensory world poses a real problem to many
autistic children, who seem overwhelmed by their own
senses. A child with autism may ignore objects or become
obsessed with them, continually watching the object
or the movement of his fingers over it. Many of these
children may react to sounds by banging their head
or flapping fingers. Some high-functioning autistic
adults who have written books about their childhood
experiences report that sounds were often excruciatingly
painful to them, forcing them to withdraw from their
environment or try to cope by withdrawing into their
own world of sensation and movement.
Intellectual problems
Most autistic children appear to be moderately
mentally retarded. They may giggle or cry for no
464

reason, have no fear of real danger, but exhibit terror
of harmless objects.

Diagnosis
There is no medical test for autism. Because the
symptoms of autism are so varied, the condition may
go undiagnosed for some time (especially in those with
mild cases or if other handicaps are also present).
It may be confused with other diseases, such as fragile
X syndrome, tuberous sclerosis, and untreated
phenylketonuria.
Autism is diagnosed by observing the child’s
behavior, communication skills, and social interactions. Medical tests should rule out other possible
causes of autistic symptoms. Criteria that mental
health experts use to diagnose autism include:


problems with developing friendships



problems with make-believe or social play



endlessly repeated words or strings of words



difficulty in carrying on a conversation
GALE ENCYCLOPEDIA OF MEDICINE

Antidepressants—A type of medication that is used
to treat depression; it is also sometimes used to treat
autism.
Asperger syndrome—Children who have autistic
behavior but no problems with language.
Encephalitis—A rare inflammation of the brain
caused by a viral infection. It has been linked to
the develoment of autism.
Fragile X syndrome—A genetic condition related to
the X chromosome that affects mental, physical and
sensory development.
Major tranquilizers—The family of drugs that
includes the psychotropic or neuroleptic drugs,
sometimes used to help autistic people. They carry
significant risk of side effects, including Parkinsonism
and movement disorders, and should be prescribed
with caution.
Opiate blockers—A type of drug that blocks the
effects of natural opiates in the system. This
makes some people, including some people with
autism, appear more responsive to their
environment.
Phenylketonuria (PKU)—An enzyme deficiency
present at birth that disrupts metabolism and causes
brain damage. This rare inherited defect may be
linked to the development of autism.
Rubella—Also known as German measles. When a
woman contracts rubella during pregnancy, her
developing infant may be damaged. One of the
problems that may result is autism.
Stimulants—A class of drugs, including Ritalin,
used to treat people with autism. They may make
children calmer and better able to concentrate, but
they also may limit growth or have other side
effects.
Tuberous sclerosis—A genetic disease that causes
skin problems, seizures, and mental retardation. It
may be confused with autism.



obsessions with rituals or restricted patterns



preoccupation with parts of objects

Some children have a few of the symptoms of
autism, but not enough to be diagnosed with the
‘‘classical’’ form of the condition. Children who have
autistic behavior but no problems with language may
be diagnosed with ‘‘Asperger syndrome.’’ Children
GALE ENCYCLOPEDIA OF MEDICINE

who seem normal at first but who begin to show
autistic behavior as they get older might be diagnosed
with ‘‘childhood disintegrative disorder’’ (CDD).
These problems are sometimes called ‘‘autistic spectrum disorders.’’ It is also important to rule out other
problems that seem similar to autism.

Treatment
There is no cure for autism. Treatments are
aimed at reducing specific symptoms. Because the
symptoms vary so widely from one person to the
next, there is not a single approach that works for
every person. A spectrum of interventions include
training in music, listening, vision, speech and language, and senses. Special diets and medications may
also be prescribed.
Studies show that people with autism can improve
significantly with proper treatment. A child with autism can learn best with special teachers in a
structured program that emphasizes individual
instruction. The two most-often studied types of treatment are:
Educational or behavioral treatment
Typically, behavioral techniques are used to help
the child respond and decrease symptoms. This might
include positive reinforcement (food and rewards) to
boost language and social skills. This training includes
structured, skill-oriented instruction designed to boost
social and language abilities. Training needs to begin
as early as possible, since early intervention appears to
influence brain development.
Most experts believe that modern treatment is
most effective when carried out at home, although
treatment may also take place in a psychiatric hospital, specialized school, or day care program.
Medication
No single medication has yet proved highly effective for the major features of autism. However, a
variety of drugs can control self-injurious, aggressive,
and other of the more difficult behaviors. Drugs also
can control epilepsy, which afflicts up to 20% of people with autism.
Five types of drugs are sometimes prescribed to
help the behavior problems of people with autism:


stimulants, such as methylphenidate (Ritalin)



antidepressants, such as fluroxamine (Luvox)



opiate blockers, such as naltrexone (ReVia)
465

Autism

KEY TERMS

Autoimmune disorders



antipsychotics

Resources



tranquilizers.

ORGANIZATIONS

Today, most experts recommend a complex treatment regimen that begins early and continues through
the teenage years. Behavioral therapies are used in
conjunction with medications.

Alternative treatment
Many parents report success with megavitamin
therapy. Some studies have shown that vitamin B6
improves eye contact and speech and lessens tantrum
behavior. Vitamin B6 causes fewer side effects than
other medications and is considered safe when used
in appropriate doses. However, not many health practitioners advocate its use in the treatment of autism,
citing that the studies showing its benefit were flawed.
DMG (dimethylglycine)
This compound, available in many health food
stores, is legally classified as a food, not a vitamin or
drug. Some researchers claim that it improves speech
in children with autism. Those who respond to this
treatment will usually do so within a week. Again,
many doctors do not feel that the studies are adequate
to promote this treatment.

Autism Network International. PO Box 448, Syracuse, NY
13210.
Autism Research Institute. 4182 Adams Ave., San Diego,
CA 92116. (619) 281-7165.
Autism Society of America. 7910 Woodmont Avenue, Suite
300, Bethesda, Maryland 20814-3067. (800) 328-8476.
<http://www.autism-society.org>.
National Alliance for Autism Research.
<naar@naar.org>.
National Autism Hotline. c/o Autism Services Center, PO
Box 507, 605 Ninth St., Huntington, WV 25710. (304)
525-8014.
National Fragile X Foundation. PO Box 190488, San
Francisco, CA 94119. (800) 688-8765. <http://
www.nfxf.org>.
National Institute of Neurological Disorders and Stroke. PO
Box 5801, Bethesda, MD 20824. (800) 352-9424.
<http://www.ninds.nih.gov/index.htm>.
OTHER

Autism Society of America. 7910 Woodmont Avenue.
<http://www.autism-society.org>.
National Alliance for Autism Research (NAAR). <http://
www.naar.org>.
National Information Center for Children and Youth with
Disabilities. <http://www.nichcy.org/transitn.htm>.

Carol A. Turkington

Exercise
One researcher found that vigorous exercise (20
minutes or longer, three or four days a week) seems to
decrease hyperactivity, aggression, self-injury and
other autistic symptoms.

Autograft see Skin grafting

I Autoimmune disorders

Prognosis
While there is no cure, with appropriate treatment
the negative behaviors of autism may improve. Earlier
generations placed autistic children in institutions;
today, even severely disabled children can be helped in
a less restrictive environment to develop to their highest
potential. Many can eventually become more responsive to others as they learn to understand the world
around them, and some can lead nearly normal lives.
People with autism have a normal life expectancy.
Some people with autism can handle a job; they do
best with structured jobs that involve a degree of
repetition.

Definition
Autoimmune disorders are conditions in which a
person’s immune system attacks the body’s own cells,
causing tissue destruction.

Description
Autoimmunity is accepted as the cause of a wide
range of disorders, and it is suspected to be responsible
for many more. Autoimmune diseases are classified as
either general, in which the autoimmune reaction
takes place simultaneously in a number of tissues, or
organ specific, in which the autoimmune reaction targets a single organ.

Prevention
Until the cause of autism is discovered, prevention
is not possible.
466

Autoimmune disorders include the following:


Systemic lupus erythematosus. A general autoimmune disease in which antibodies attack a number
GALE ENCYCLOPEDIA OF MEDICINE







Rheumatoid arthritis. Occurs when the immune system attacks and destroys the tissues that line bone
joints and cartilage. The disease occurs throughout
the body, although some joints may be more affected
than others.
Goodpasture’s syndrome. Occurs when antibodies
are deposited in the membranes of both the lung
and kidneys, causing both inflammation of kidney
glomerulus (glomerulonephritis) and lung bleeding. It
is typically a disease of young males.
Grave’s disease. Caused by an antibody that binds to
specific cells in the thyroid gland, causing them to
make excessive amounts of thyroid hormone.



Hashimoto’s thyroiditis. Caused by an antibody that
binds to cells in the thyroid gland. Unlike in Grave’s
disease, however, this antibody’s action results in less
thyroid hormone being made.



Pemphigus vulgaris. A group of autoimmune disorders that affect the skin.



Myasthenia gravis. A condition in which the immune
system attacks a receptor on the surface of muscle
cells, preventing the muscle from receiving nerve
impulses and resulting in severe muscle weakness.



Scleroderma. Also called CREST syndrome or progressive systemic sclerosis, scleroderma affects the
connective tissue.



Autoimmune hemolytic anemia. Occurs when the
body produces antibodies that coat red blood cells.



Autoimmune thrombocytopenic purpura. Disorder
in which the immune system targets and destroys
blood platelets.



Polymyositis and Dermatomyositis. Immune disorders that affect the neuromuscular system.



Pernicious anemia. Disorder in which the immune
system attacks the lining of the stomach in such a
way that the body cannot metabolize vitamin B12.



Sjögren’s syndrome. Occurs when the exocrine
glands are attacked by the immune system, resulting
in excessive dryness.



Ankylosing spondylitis. Immune system induced
degeneration of the joints and soft tissue of the spine.



Vasculitis. A group of autoimmune disorders in
which the immune system attacks and destroys
blood vessels.



Type I diabetes mellitus. May be caused by an antibody that attacks and destroys the islet cells of the
pancreas, which produce insulin.

GALE ENCYCLOPEDIA OF MEDICINE



Amyotrophic lateral schlerosis. Also called Lou
Gehrig’s disease. An immune disorder that causes
the death of neurons which leads to progressive loss
of muscular control.



Guillain-Barre syndrome. Also called infectious
polyneuritis. Often occurring after an infection or
an immunization (specifically Swine flu), the disease
affects the myelin sheath, which coats nerve cells. It
causes progressive muscle weakness and paralysis.



Multiple sclerosis. An autoimmune disorder that may
involve a virus affects the central nervous system,
causing loss of coordination and muscle control.

Causes and symptoms
To further understand autoimmune disorders, it is
helpful to understand the workings of the immune
system. The purpose of the immune system is to defend
the body against attack by infectious microbes (germs)
and foreign objects. When the immune system attacks
an invader, it is very specific—a particular immune
system cell will only recognize and target one type of
invader. To function properly, the immune system must
not only develop this specialized knowledge of individual invaders, but it must also learn how to recognize
and not destroy cells that belong to the body itself.
Every cell carries protein markers on its surface that
identifies it in one of two ways: what kind of cell it is
(e.g. nerve cell, muscle cell, blood cell, etc.) and to
whom that cell belongs. These markers are called
major histocompatability complexes (MHCs). When
functioning properly, cells of the immune system will
not attack any other cell with markers identifying it as
belonging to the body. Conversely, if the immune system cells do not recognize the cell as ‘‘self,’’ they attach
themselves to it and put out a signal that the body has
been invaded, which in turn stimulates the production
of substances such as antibodies that engulf and destroy
the foreign particles. In case of autoimmune disorders,
the immune system cannot distinguish between ‘‘self’’
cells and invader cells. As a result, the same destructive
operation is carried out on the body’s own cells that
would normally be carried out on bacteria, viruses, and
other such harmful entities.
The reasons why immune systems become dysfunctional in this way is not well understood.
However, most researchers agree that a combination
of genetic, environmental, and hormonal factors
play into autoimmunity. Researchers also speculate
that certain mechanisms may trigger autoimmunity.
First, a substance that is normally restricted to one
part of the body, and therefore not usually exposed
to the immune system, is released into other areas
467

Autoimmune disorders

of different tissues. The disease recurs periodically
and is seen mainly in young and middle-aged women.

Autoimmune disorders



Myasthenia gravis. Characterized by fatigue and muscle weakness that at first may be confined to certain
muscle groups, but then may progress to the point of
paralysis. Myasthenia gravis patients often have
expressionless faces as well as difficulty chewing and
swallowing. If the disease progresses to the respiratory
system, artificial respiration may be required.



Scleroderma. Disorder is usually preceded by
Raynaud’s phenomenon. Symptoms that follow
include pain, swelling, and stiffness of the joints,
and the skin takes on a tight, shiny appearance. The
digestive system also becomes involved, resulting in
weight loss, appetite loss, diarrhea, constipation, and
distention of the abdomen. As the disease progresses,
the heart, lungs, and kidneys become involved, and
malignant hypertension causes death in approximately 30% of cases.



Autoimmune hemolytic anemia. May be acute or
chronic. Symptoms include fatigue and abdominal
tenderness due to an enlarged spleen.



Autoimmune thrombocytopenic purpura. Characterized by pinhead-size red dots on the skin, unexplained
bruises, bleeding from the nose and gums, and blood in
the stool.



Polymyositis and Dermatomyositis. In polymyositis,
symptoms include muscle weakness, particularly in
the shoulders or pelvis, that prevents the patient from
performing everyday activities. In dermatomyositis,
the same muscle weakness is accompanied by a rash
that appears on the upper body, arms, and fingertips.
A rash may also appear on the eyelids, and the area
around the eyes may become swollen.



Pernicious anemia. Signs of pernicious anemia
include weakness, sore tongue, bleeding gums, and
tingling in the extremities. Because the disease causes
a decrease in stomach acid, nausea, vomiting, loss of
appetite, weight loss, diarrhea, and constipation are
possible. Also, because Vitamin B12 is essential for
the nervous system function, the deficiency of it
brought on by the disease can result in a host of
neurological problems, including weakness, lack of
coordination, blurred vision, loss of fine motor skills,
loss of the sense of taste, ringing in the ears, and loss
of bladder control.



Sjögren’s syndrome. Characterized by excessive dryness of the mouth and eyes.



Ankylosing spondylitis. Generally begins with lower
back pain that progresses up the spine. The pain may
eventually become crippling.



Vasculitis. Symptoms depend upon the group of
veins affected and can range greatly.

KEY TERMS
Autoantibody—An antibody made by a person that
reacts with their own tissues.
Paresthesias— A prickly, tingling sensation.

where it is attacked. Second, the immune system
may mistake a component of the body for a similar
foreign component. Third, cells of the body may be
altered in some way, either by drugs, infection, or
some other environmental factor, so that they are
no longer recognizable as ‘‘self’’ to the immune
system. Fourth, the immune system itself may be
damaged, such as by a genetic mutation, and therefore cannot function properly.
The symptoms of the above disorders include:




Systemic lupus erythematosus. Symptoms include
fever, chills, fatigue, weight loss, skin rashes (particularly the classic ‘‘butterfly’’ rash on the face), vasculitis, polyarthralgia, patchy hair loss, sores in the mouth
or nose, lymph-node enlargement, gastric problems,
and, in women, irregular periods. About half of those
who suffer from lupus develop cardiopulmonary problems, and some may also develop urinary problems.
Lupus can also effect the central nervous system,
causing seizures, depression, and psychosis.
Rheumatoid arthritis. Initially may be characterized
by a low-grade fever, loss of appetite, weight loss,
and a generalized pain in the joints. The joint pain
then becomes more specific, usually beginning in the
fingers, then spreading to other areas, such as the
wrists, elbows, knees, and ankles. As the disease
progresses, joint function diminishes sharply and
deformities occur, particularly the characteristic
‘‘swan’s neck’’ curling of the fingers.



Goodpasture’s syndrome. Symptoms are similar to
that of iron deficiency anemia, including fatigue and
pallor. Symptoms involving the lungs may range
from a cough that produces bloody sputum to outright hemorrhaging. Symptoms involving the urinary system include blood in the urine and/or swelling.



Grave’s disease. This disease is characterized by an
enlarged thyroid gland, weight loss without loss of
appetite, sweating, heart palpitations, nervousness,
and an inability to tolerate heat.



Hashimoto’s thyroiditis. This disorder generally displays no symptoms.



Pemphigus vulgaris. This disease is characterized by
blisters and deep lesions on the skin.

468

GALE ENCYCLOPEDIA OF MEDICINE

Type I diabetes mellitus. Characterized by fatigue
and an abnormally high level of glucose in the
blood (hyperglycemia).



Amyotrophic lateral schlerosis. First signs are stumbling and difficulty climbing stairs. Later, muscle
cramps and twitching may be observed as well as
weakness in the hands making fastening buttons or
turning a key difficult. Speech may become slowed or
slurred. There may also be difficluty swallowing. As
respiratory muscles atrophy, there is increased danger of aspiration or lung infection.



Guillain-Barre syndrome. Muscle weakness in the legs
occurs first, then the arms and face. Paresthesias (a
prickly, tingling sensation) is also felt. This disorder
affects both sides of the body and may involve paralysis and the muscles that control breathing.



Multiple sclerosis. Like Lou Gehrig’s disease, the
first symptom may be clumsiness. Weakness or
exhaustion is often reported, as well as blurry or
double vision. There may be dizziness, depression,
loss of bladder control, and muscle weakness so
severe that the patient is confined to a wheelchair.

Diagnosis
A number of tests are involved in the diagnosis
of autoimmune diseases, depending on the particular
disease; e.g. blood tests, cerebrospinal fluid analysis,
electromylogram (measures muscle function), and
magnetic resonance imaging of the brain. Usually,
these tests determine the location and extent of
damage or involvement. They are useful in charting
progress of the disease and as baselines for
treatment.
The principle tool, however, for authenticating
autoimmune disease is antibody testing. Such tests
involve measuring the level of antibodies found in
the blood and determining if they react with specific
antigens that would give rise to an autoimmune reaction. An elevated amount of antibodies indicates that
a humoral immune reaction is occurring. Since elevated antibody levels are also seen in common infections, they must be ruled out as the cause for the
increased antibody levels.
Antibodies can also be typed by class. There are
five classes of antibodies, and they can be separated in
the laboratory. The class IgG is usually associated
with autoimmune diseases. Unfortunately, IgG class
antibodies are also the main class of antibody seen in
normal immune responses.
The most useful antibody tests involve introducing the patient’s antibodies to samples of his or her
GALE ENCYCLOPEDIA OF MEDICINE

own tissue, usually thyroid, stomach, liver, and kidney
tissue. If antibodies bind to the ‘‘self’’ tissue, it is
diagnostic for an autoimmune disorder. Antibodies
from a person without an autoimmune disorder
would not react to ‘‘self ’’ tissue.

Treatment
Treatment of autoimmune diseases is specific to
the disease, and usually concentrates on alleviating or
preventing symptoms rather than correcting the
underlying cause. For example, if a gland involved in
an autoimmune reaction is not producing a hormone
such as insulin, administration of that hormone is
required. Administration of a hormone, however,
will restore the function of the gland damaged by the
autoimmune disease.
The other aspect of treatment is controlling the
inflammatory and proliferative nature of the immune
response. This is generally accomplished with two
types of drugs. Steroid compounds are used to control
inflammation. There are many different steroids, each
having side effects. The proliferative nature of the
immune response is controlled with immunosuppressive drugs. These drugs work by inhibiting the replication of cells and, therefore, also suppress non-immune
cells leading to side effects such as anemia.
Systemic enzyme therapy is a new treatment that is
showing results for rheumatoid arthritis, multiple
sclerosis, ankylosing spondylitis, and other inflammatory diseases. Enzymes combinations of pancreatin,
trypsin, chymotrypsin, bromelain, and papain help
stimulate the body’s own defenses, accelerate inflammation in order to reduce swelling and improve circulation, and break up the immune complexes within the
bloodstream. Symptoms have been reduced using this
treatment.
Other treatments that hold some promise are irradiation of the spleen and gene therapy. Splenic irradiation is touted to be a safe, alternative for patients with
autoimmune blood diseases, especially autoimmune
hemolytic anemia, or others with compromised
immune systems, such as HIV patients and the elderly.
It is reported to have few side effects and seems to be
working. Cytokine and cytokine inhibitor genes
injected directly into muscle tissue also appear to be
effective in treating Type I diabetes mellitus, systemic
lupus erythematosus, thyroditis, and arthritis.

Prognosis
Prognosis depends upon the pathology of each
autoimmune disease.
469

Autoimmune disorders



Autopsy

Prevention
Most autoimmune diseases cannot be prevented.
Though the mechanisms involved in how these diseases affect the body are known, it is still unclear
why the body turns on itself. Since more women than
men seem to be affected by some of these disorders
(e.g. lupus), some researchers are looking into hormones as a factor. This, and gene therapy, may be
the preventatives of the future.
Resources
PERIODICALS

Cichoke, Anthony J. ‘‘Natural Relief for Autoimmune
Disorders.’’ Better Nutrition. 62, no. 6 (June 2000): 24.
Henderson, Charles W. ‘‘Gene Therapy Uses Vectors
EncodingCytokines or Cytokine Inhibitors (for
treatment of autoimmune disorders).’’
ImmunotherapyWeekly September 27, 2000: pNA.
Riccio, Nina M. ‘‘Autoimmune Disorder: When the Body
AttacksItself.’’ Current Health 2 26, no. 5 (January
2000): 13.
‘‘Splenic Irradiation Is an Option for Patients with
AutoimmuneDisorders and Those with HIV.’’ AIDS
Weekly (April 9, 2001): pNA.

Janie F. Franz

Autoimmune hepatitis see Hepatitis,
autoimmune
Autologous transfusion see Transfusion
Autologous transplant see Bone marrow
transplantation
Automatic implantable cardioverterdefibrillator see Implantable cardioverterdefibrillator

I Autopsy
Definition
An autopsy is a postmortem assessment or examination of a body to determine the cause of death. An
autopsy is performed by a physician trained in
pathology.

KEY TERMS
Acquired immunodeficiency syndrome (AIDS) —
A group of diseases resulting from infection with
the human immunodeficiency virus (HIV). A person infected with HIV gradually loses immune
function, becoming less able to resist aliments and
cancers, resulting in eventual death.
Computed tomography scan (CT scan) —The technique used in diagnostic studies of internal bodily
structures in the detection of tumors or brain aneurysms. This diagnostic test consists of a computer
analysis of a series of cross-sectional scans made
along a single axis of a bodily structure or tissue that
is used to construct a three-dimensional image of
that structure
Creutzfeld-Jakob disease—A rare, often fatal disease of the brain, characterized by gradual dementia and loss of muscle control that occurs most often
in middle age and is caused by a slow virus.
Hepatitis—Inflammation of the liver, caused by
infectious or toxic agents and characterized by jaundice, fever, liver enlargement, and abdominal pain.
Magnetic resonance imaging (MRI)—A diagnostic
tool that utilizes nuclear magnetic energy in the
production of images of specific atoms and molecular structures in solids, especially human cells,
tissues, and organs.
Postmortem—After death.

discover the pathway of a disease, and provide valuable
information to be used in the care of the living. When
foul play is suspected, a government coroner or medical
examiner performs autopsies for legal use. This branch
of medical study is called forensic medicine. Forensic
specialists investigate deaths resulting from violence
or occurring under suspicious circumstances.
Benefits of research from autopsies include the
production of new medical information on diseases
such as toxic shock syndrome, acquired immunodeficiency syndrome (AIDS). Organ donation, which can
potentially save the lives of other patients, is also
another benefit of autopsies.

Precautions
Purpose
Most autopsies advance medical knowledge and
provide evidence for legal action. Medically, autopsies
determine the exact cause and circumstances of death,
470

When performed for medical reasons, autopsies
require formal permission from family members or the
legal guardian. (Autopsies required for legal reasons
when foul play is suspected do not need the consent
GALE ENCYCLOPEDIA OF MEDICINE

Description
An autopsy can be described as the examination
of a deceased human body with a detailed exam of
the person’s remains. This procedure dates back to
the Roman era when few human dissections were
performed; autopsies were utilized, however, to
determine the cause of death in criminal cases. At
the beginning of the procedure the exterior body is
examined and then the internal organs are removed
and studied. Some pathologists argue that more
autopsies are performed than necessary. However,
recent studies show that autopsies can detect major
findings about a person’s condition that were not
suspected when the person was alive. And the growing awareness of the influence of genetic factors in
disease has also emphasized the importance of
autopsies.
Despite the usefulness of autopsies, fewer autopsies have been performed in the United States during
the past 10-20 years. A possible reason for this decline
is concern about malpractice suits on the part of the
treating physician. Other possible reasons are that
hospitals are performing fewer autopsies because of
the expense or because modern technology, such as
CT scans and magnetic resonance imaging, can
often provide sufficient diagnostic information.
Nonetheless, federal regulators and pathology groups
have begun to establish new guidelines designed to
increase the number and quality of autopsies being
performed.
Many experts are concerned that if the number of
autopsies increases, hospitals may be forced to charge
families a fee for the procedure as autopies are not
normally covered by insurance companies or
Medicare. Yet, according to several pathologists, the
benefit of the procedure for families and doctors does
justify the cost. In medical autopsies, physicians
remain cautious to examine only as much of the
body as permitted according to the wishes of the
family. It is important to note that autopsies can also
provide peace of mind for the bereaved family in certain situations.

Preparation
If a medical autopsy is being performed, written
permission is secured from the family of the deceased
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
Once the autopsy has been completed, the body is
prepared for final arrangements according to the
family’s wishes

Risks
There are some risks of disease transmission from
the deceased. In fact, some physicans may refuse to do
autopsies on specific patients because of a fear of
contracting diseases such as AIDS, hepatitis, or
Creutzfeld-Jakob disease.

Normal results
In most situations the cause of death is determined
from the procedure of an autopsy without any transmission of disease.

Abnormal results
Abnormal results would include inconclusive
results from the autopsy and transmission of infectious disease during the autopsy.
Resources
ORGANIZATIONS

American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://www.amaassn.org>.

Jeffrey P. Larson, RPT

I Aviation medicine
Definition
Also known as aerospace medicine, flight medicine, or space medicine, aviation medicine is a medical specialty that focuses on the physical and
psychological conditions associated with flying and
space travel.

Purpose
Since flying airplanes and spacecraft involves
great risk and physical demands, such as changes in
gravity and oxygen, pilots and astronauts need medical experts to protect their safety and the public’s
safety.
471

Aviation medicine

of next of kin.) During the autopsy, very concise notes
and documentation must be made for both medical
and legal reasons. Some religious groups prohibit
autopsies.

Aviation medicine

KEY TERMS
G suits—Special flight suits, worn by fighter pilots,
which have compartments that fill with air or fluid
to keep blood from pooling in the lower body during rapid acceleration and tight turns.
Hypoxia—Hypoxia, or altitude sickness, reduces
the amount of oxygen in the brain causing such
symptoms as dizziness, shortness of breath, and
mental confusion.
Tympanic membrane—A structure in the middle
ear that can rupture if pressure in the ear is
not equalized during airplane ascents and
descents.
Valsalva Maneuver —Pilots grunt and tighten their
abdominal muscles to prevent black outs during
high-performance flying.

Description
Pressure changes
In the United States, the Federal Aviation
Administration (FAA) requires all pilots who fly
above 14,500 ft (4,420 m) to be prepared for pressure
changes caused by lower oxygen levels at high altitude.
Pilots must either have a pressurized cabin or access to
an oxygen mask. Without these protections, they
could experience hypoxia, or altitude sickness.
Hypoxia reduces the amount of oxygen in the brain,
causing such symptoms as dizziness, shortness of
breath, and mental confusion. These symptoms
could cause the pilot to lose control of the plane.
Hypoxia can be treated with oxygen therapy.
Rapid altitude increases and decreases can cause
pain because there is an air pocket in the middle portion of the ear. To equalize pressure in the ear, physicians typically advise pilots and passengers to clear
their sinuses by plugging their nose and blowing until
the eardrums ‘‘pop.’’ Other options include yawning,
swallowing or chewing gum. For people with a cold or
a severely blocked middle ear, the use of decongestants,
antihistamines, or nasal sprays may help. Without taking steps to equalize pressure, the tympanic membrane
could rupture, causing hearing loss, vertigo, dizziness,
and nausea.
Gravity’s impact
Fighter pilots who fly high-performance jets can
experience health problems during rapid acceleration
472

and when executing tight turns at high speed. During
these moves, a pilot experiences extreme gravity conditions that can pull blood away from the brain and
heart and into the lower body. This can cause the pilot
to have tunnel vision or pass out. To prevent these
potentially deadly situations, the military requires
fighter pilots to wear special flight suits, or G suits,
which have compartments that fill with air or fluid to
keep blood from pooling in the lower body.
Some pilots, like the Blue Angels, use a technique
called the Valsalva Maneuver instead of G suits to
prevent black outs during high-performance flying.
The Valsalva Maneuver involves grunting and tightening the abdominal muscles to stop blood from
collecting in the wrong parts of the body.
PREVENTIVE CARE. Since any routine health problem that affects a pilot could mean the loss of
hundreds of lives, aviation medicine specialists who
work for commercial airlines and the military take
special care to educate pilots about proper diet,
exercise and preventive health tools. For example,
physicians may frequently screen pilots for vision
changes caused by glaucoma or cataracts. They
also will check for hearing loss and encourage the
pilot to wear earplugs or headphones to buffer
engine noise. To monitor for heart disease, physicians will check blood pressure and may order diagnostic tests such as an ECG or stress test.

Motion sickness
Many people experience nausea, vertigo, and disorientation when they first arrive in space. This is
caused by changes in the fluid in the inner ear, which
is sensitive to gravity and affects our sense of spatial
orientation. The symptoms typically ease after several
days, but often recur when the astronaut returns to
Earth. To treat this condition, physicians give astronauts motion sickness medication, such as lorazepam.
Bone and muscle loss
In zero-gravity conditions, astronauts lose bone
and muscle mass. On earth, the natural resistance of
gravity helps build stronger muscles and bones during
normal weight-bearing activities like walking or even
sitting at a desk. In space, however, astronauts must
work harder to prevent bone and muscle loss. Exercise
is an important treatment. Crew members may use an
exercise cycle or resistive rubber bands to stay in
shape. Physicians also may give them medication to
prevent bone loss and prescribe nutritional supplements, such as a mixture of essential amino acids and
carbohydrates, to limit muscle atrophy.
GALE ENCYCLOPEDIA OF MEDICINE

Another health threat to space travelers is radiation. Harmful rays can alter the DNA in human cells
and cause cancer. Excess radiation also can weaken
the immune system. To prevent these problems, physicians may give astronauts nutritional supplements.
For example, research has show that n-3 fatty acids
found in fish oil reduce DNA damage.
Cardiovascular issues
When astronauts return to earth after a long mission, they tend to feel dizzy and black out. Scientists are
concerned about this dilemma because it could be dangerous if the crew members need to make an emergency
exit. One way to prevent this problem, which is caused
by a drop in blood pressure, is to have the astronauts
drink extra fluids and increase salt intake to increase
blood volume. Physicians also may prescribe medication
that causes blood vessels to contract. As another precaution, astronauts also put on protective flight suits, or
G suits, before they re-enter the earth’s atmosphere.
Resources
PERIODICALS

Aviation, Space and Environmental Medicine. Monthly peerreviewed journal published by the Aerospace Medical
Association. Contact theeditor: 3212 Swandale Dr.,
San Antonio, TX 78230-4404. (210) 342-5670.
ASEMJournal@worldnet.att.net.
ORGANIZATIONS

Aerospace Medical Association. 320 S. Henry St.,
Alexandria, VA 22314-3579. (703) 739-2240. <http://
www.asma.org>.
National Space Biomedical Research Institute. One Baylor
Plaza, NA-425, Houston, TX 77030. (713) 798-7412.
info@www.nsbri.org. <http://www.nsbri.org>.
Wright State University Aerospace Medicine Program. P.O.
Box 92, Dayton, Ohio 45401-0927. (937) 276-8338.
<http://www.med.wright.edu>.
OTHER

Federal Aviation Administration Office of Aviation
Medicine. <http://www.faa.gov/avr/aamhome.htm>.
National Aeronautics and Space Administration Aerospace
Medicine. <http://spacelink.msfc.nasa.gov>.
Society of USAF Flight Surgeons Online Catalog. <http://
www.sam.brooks.af.mil/ram/rammain.htm>.

Melissa Knopper

AVM see Arteriovenous malformations
Avoidant personality disorder see
Personality disorders
Avulsions see Wounds
GALE ENCYCLOPEDIA OF MEDICINE

I Ayurvedic medicine
Definition
Ayurvedic medicine is a system of healing that originated in ancient India. In Sanskrit, ayur means life or
living, and veda means knowledge, so Ayurveda has been
defined as the ‘‘knowledge of living’’ or the ‘‘science of
longevity.’’ Ayurvedic medicine utilizes diet, detoxification and purification techniques, herbal and mineral
remedies, yoga, breathing exercises, meditation, and
massage therapy as holistic healing methods. Ayurvedic
medicine is widely practiced in modern India and has
been steadily gaining followers in the West.

Purpose
According to the original texts, the goal of
Ayurveda is prevention as well as promotion of the
body’s own capacity for maintenance and balance.
Ayurvedic treatment is non-invasive and non-toxic, so
it can be used safely as an alternative therapy or alongside conventional therapies. Ayurvedic physicians
claim that their methods can also help stress-related,
metabolic, and chronic conditions. Ayurveda has been
used to treat acne, allergies, asthma, anxiety, arthritis,
chronic fatigue syndrome, colds, colitis, constipation,
depression, diabetes, flu, heart disease, hypertension,
immune problems, inflammation, insomnia, nervous
disorders, obesity, skin problems, and ulcers.
Ayurvedic physicians seek to discover the roots
of a disease before it gets so advanced that more
radical treatments are necessary. Thus, Ayurveda
seems to be limited in treating severely advanced
conditions, traumatic injuries, acute pain, and conditions and injuries requiring invasive surgery.
Ayurvedic techniques have also been used alongside
chemotherapy and surgery to assist patients in
recovery and healing.

Description
Origins
Ayurvedic medicine originated in the early civilizations of India some 3,000-5,000 years ago. It is
mentioned in the Vedas, the ancient religious and
philosophical texts that are the oldest surviving literature in the world, which makes Ayurvedic medicine
the oldest surviving healing system. According to the
texts, Ayurveda was conceived by enlightened wise
men as a system of living harmoniously and maintaining the body so that mental and spiritual awareness
could be possible. Medical historians believe that
473

Ayurvedic medicine

Radiation

Ayurvedic medicine

D E E P A K C H O P R A (1946– )
University and Boston University schools of medicine—
while establishing a very successful private practice. By
the time he was thirty-five, Chopra had become chief of
staff at New England Memorial Hospital.
Disturbed by Western medicine’s reliance on medication, he began a search for alternatives and discovered one
in the teachings of the Maharishi Mahesh Yogi, an Indian
spiritualist who had gained a cult following in the late sixties
teaching Transcendental Meditation (TM). Chopra began
practicing TM fervently and eventually met the Maharishi.
In 1985 Chopra established the Ayurvedic Health Center for
Stress Management and Behavioral Medicine in Lancaster,
Massachusetts, where he began his practice of integrating
the best aspects of Eastern and Western medicine.

(AP/Wide World Photos. Reproduced by permission.)

Deepak Chopra was born in India and studied medicine at the All India Institute of Medical Science. He left his
home for the United States in 1970 and completed residencies in internal medicine and endocrinology. He went
on to teaching posts at major medical institutions—Tufts

Ayurvedic ideas were transported from ancient India
to China and were instrumental in the development of
Chinese medicine.
Today, Ayurvedic medicine is used by 80% of the
population in India. Aided by the efforts of Deepak
Chopra and the Maharishi, it has become an increasingly accepted alternative medical treatment in
America during the last two decades. Chopra is an
M.D. who has written several bestsellers based on
Ayurvedic ideas. He also helped develop the Center
for Mind/Body Medicine in La Jolla, California, a
major Ayurvedic center that trains physicians in
Ayurvedic principles, produces herbal remedies, and
conducts research and documentation of its healing
techniques.
Key ideas
To understand Ayurvedic treatment, it is necessary
to have an idea how the Ayurvedic system views the
body. The basic life force in the body is prana, which is
also found in the elements and is similar to the Chinese
474

In 1993, he published Creating Affluence: Wealth
Consciousness in the Field of All Possibilities, and the enormously successful best seller, Ageless Body, Timeless Mind.
In the latter he presents his most radical thesis: that aging is
not the inevitable deterioration of organs and mind that we
have been traditionally taught to think of it as. It is a process
that can be influenced, slowed down, and even reversed
with the correct kinds of therapies, almost all of which are
self-administered or self-taught. He teaches that applying a
regimen of nutritional balance, meditation, and emotional
clarity characterized by such factors as learning to easily
and quickly express anger, for instance, can lead to
increased lifespans of up to 120 years.

notion of chi. As Swami Vishnudevananda, a yogi and
expert, put it, ‘‘Prana is in the air, but is not the oxygen,
nor any of its chemical constituents. It is in food, water,
and in the sunlight, yet it is not vitamin, heat, or lightrays. Food, water, air, etc., are only the media through
which the prana is carried.’’
In Ayurveda, there are five basic elements that
contain prana: earth, water, fire, air, and ether.
These elements interact and are further organized in
the human body as three main categories or basic
physiological principles in the body that govern all
bodily functions known as the doshas. The three
doshas are vata, pitta, and kapha. Each person has a
unique blend of the three doshas, known as the person’s prakriti, which is why Ayurvedic treatment is
always individualized. In Ayurveda, disease is viewed
as a state of imbalance in one or more of a person’s
doshas, and an Ayurvedic physician strives to adjust
and balance them, using a variety of techniques.
The vata dosha is associated with air and ether,
and in the body promotes movement and lightness.
GALE ENCYCLOPEDIA OF MEDICINE

Physical
characteristics

Emotional
characteristics

Behavioral
characteristics

Vata

Pitta

Kapha

Thin.
Prominent
features.
Cool, dry
skin.
Constipation.
Cramps.

Average
build. Fair,
thin hair.
Warm, moist
skin. Ulcers,
heartburn,
and hemorrhoids. Acne.
Intense.
Quick tempered.
Intelligent.
Loving.
Articulate.
Orderly.
Structured
sleep and
meal times.
Perfectionist.

Large build.
Wavy, thick
hair. Pale, cool,
oily skin.
Obesity, allergies, and sinus
problems. High
cholesterol.
Relaxed. Not
easily angered.
Affectionate.
Tolerant.
Compassionate.

Moody.
Vivacious.
Imaginative.
Enthusiastic.
Intuitive.
Unscheduled
sleep and
meal times.
Nervous disorders.
Anxiety.

Slow, graceful.
Long sleeper
and slow eater.
Procrastination.

Vata people are generally thin and light physically,
dry-skinned, and very energetic and mentally restless.
When vata is out of balance, there are often nervous
problems, hyperactivity, sleeplessness, lower back
pains, and headaches.
Pitta is associated with fire and water. In the body,
it is responsible for metabolism and digestion. Pitta
characteristics are medium-built bodies, fair skin,
strong digestion, and good mental concentration.
Pitta imbalances show up as anger and aggression
and stress-related conditions like gastritis, ulcers,
liver problems, and hypertension.
The kapha dosha is associated with water and
earth. People characterized as kapha are generally
large or heavy with more oily complexions. They
tend to be slow, calm, and peaceful. Kapha disorders
manifest emotionally as greed and possessiveness, and
physically as obesity, fatigue, bronchitis, and sinus
problems.
Diagnosis
In Ayurvedic medicine, disease is always seen as
an imbalance in the dosha system, so the diagnostic
process strives to determine which doshas are
underactive or overactive in a body. Diagnosis is
often taken over a course of days in order for the
Ayurvedic physician to most accurately determine
what parts of the body are being affected. To diagnose problems, Ayurvedic physicians often use
long questionnaires and interviews to determine a
GALE ENCYCLOPEDIA OF MEDICINE

Dosha—One of three constitutional types, either
vata, pitta, or kapha, found in Ayurvedic medicine.
Meditation—Technique of calming the mind.
Panchakarma—Intensive Ayurvedic cleansing and
detoxification program.
Prakriti—An individual’s unique dosha pattern.
Prana—Basic life energy found in the elements.
Yoga—System of body and breathing exercises.

person’s dosha patterns and physical and psychological histories. Ayurvedic physicians also intricately
observe the pulse, tongue, face, lips, eyes, and fingernails for abnormalities or patterns that they
believe can indicate deeper problems in the internal
systems. Some Ayurvedic physicians also use
laboratory tests to assist in diagnosis.
Treatment
Ayurvedic treatment seeks to re-establish balance
and harmony in the body’s systems. Usually the first
method of treatment involves some sort of detoxification and cleansing of the body, in the belief that accumulated toxins must be removed before any other
methods of treatment will be effective. Methods of
detoxification include therapeutic vomiting, laxatives,
medicated enemas, fasting, and cleansing of the
sinuses. Many Ayurvedic clinics combine all of these
cleansing methods into intensive sessions known as
panchakarma. Panchakarma can take several days or
even weeks and they are more than elimination therapies. They also include herbalized oil massage and
herbalized heat treatments. After purification,
Ayurvedic physicians use herbal and mineral remedies
to balance the body as well. Ayurvedic medicine contains a vast knowledge of the use of herbs for specific
health problems.
Ayurvedic medicine also emphasizes how people
live their lives from day to day, believing that proper
lifestyles and routines accentuate balance, rest, diet,
and prevention. Ayurveda recommends yoga as a
form of exercise to build strength and health, and
also advises massage therapy and self-massage as
ways of increasing circulation and reducing stress.
Yogic breathing techniques and meditation are also
part of a healthy Ayurvedic regimen, to reduce stress
and improve mental energy.
475

Ayurvedic medicine

KEY TERMS

Ayurvedic Body Types

Ayurvedic medicine

Of all treatments, though, diet is one of the most
basic and widely used therapy in the Ayurvedic system. An Ayurvedic diet can be a very well planned and
individualized regimen. According to Ayurveda, there
are six basic tastes: sweet, sour, salty, pungent, bitter,
and astringent. Certain tastes and foods can either
calm or aggravate a particular dosha. For instance,
sweet, sour, and salty decrease vata problems and
increase kapha. Sour, salty, and pungent can increase
pitta. After an Ayurvedic physician determines a person’s dosha profile, they will recommend a specific
diet to correct imbalances and increase health. The
Ayurvedic diet emphasizes primarily vegetarian
foods of high quality and freshness, tailored to the
season and time of day. Cooling foods are eaten in
the summer and heating ones in the winter, always
within a person’s dosha requirements. In daily routine,
the heaviest meal of the day should be lunch, and
dinner should eaten well before bedtime, to allow for
complete digestion. Also, eating meals in a calm manner with proper chewing and state of mind is important, as is combining foods properly and avoiding
overeating.
Cost
Costs of Ayurvedic treatments can vary, with
initial consultations running anywhere from $40 to
over $100, with follow-up visits costing less. Herbal
treatments may cost from $10 to $50 per month, and
are often available from health food or bulk herb
stores. Some clinics offer panchakarma, the intensive
Ayurvedic detoxification treatment, which can include
overnight stays for up to several weeks. The prices for
these programs can vary significantly, depending on
the services and length of stay. Insurance reimbursement may depend on whether the primary physician is
a licensed M.D.

Preparations
Ayurveda is a mind/body system of health that
contains some ideas foreign to the Western scientific model. Those people considering Ayurveda
should approach it with an open mind and willingness to experiment. Also, because Ayurveda is a
whole-body system of healing and health, patience
and discipline are helpful, as some conditions and
diseases are believed to be brought on by years of
bad health habits and require time and effort to
correct. Finally, the Ayurvedic philosophy believes
that each person has the ability to heal themselves,
so those considering Ayurveda should be prepared
to bring responsibility and participation into the
treatment.
476

Precautions
An Ayurvedic practitioner should always be
consulted.

Side effects
During Ayurvedic detoxification programs, some
people report fatigue, muscle soreness, and general
sickness. Also, as Ayurveda seeks to release mental
stresses and psychological problems from the patient,
some people can experience mental disturbances and
depression during treatment, and psychological counseling may be part of a sound program.

Research and general acceptance
Because Ayurveda had been outside the Western
scientific system for years, research in the United
States is new. Another difficulty in documentation
arises because Ayurvedic treatment is very individualized; two people with the same disease but different
dosha patterns might be treated differently. Much
more scientific research has been conducted over the
past several decades in India. Much research in the
United States is being supported by the Maharishi
Ayur-Ved organization, which studies the Ayurvedic
products it sells and its clinical practices.
Some Ayurvedic herbal mixtures have been proven to have high antioxidant properties, much stronger than vitamins A, C, and E, and some have also
been shown in laboratory tests to reduce or eliminate
tumors in mice and to inhibit cancer growth in human
lung tumor cells. In a 1987 study at MIT, an Ayurvedic
herbal remedy was shown to significantly reduce colon
cancer in rats. Another study was performed in the
Netherlands with Maharishi Ayur-Ved products. A
group of patients with chronic illnesses, including
asthma, chronic bronchitis, hypertension, eczema,
psoriasis, constipation, rheumatoid arthritis, headaches, and non-insulin dependent diabetes mellitus,
were given Ayurvedic treatment. Strong results were
observed, with nearly 80% of the patients improving
and some chronic conditions being completely cured.
Other studies have shown that Ayurvedic therapies
can significantly lower cholesterol and blood pressure in
stress-related problems. Diabetes, acne, and allergies
have also been successfully treated with Ayurvedic remedies. Ayurvedic products have been shown to increase
short-term memory and reduce headaches. Also,
Ayurvedic remedies have been used successfully to support the healing process of patients undergoing chemotherapy, as these remedies have been demonstrated
to increase immune system activity.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Lad, Dr. Vasant. The Complete Book of Ayurvedic Home
Remedies. Minneapolis: Three Rivers Press, 1999.
ORGANIZATIONS

American Institute of Vedic Studies. P.O. Box 8357, Santa
Fe, NM 87504. (505) 983-9385
Ayurveda Holistic Center. Bayville, Long Island, NY.
(516)759-7731 mail@Ayurvedahc.com <http://
www.Ayurvedahc.com>.
Ayurvedic and Naturopathic Medical Clinic. 10025 NE 4th
Street, Bellevue, WA 98004. (206)453-8022.
Ayurvedic Institute. 11311 Menaul, NE Albuquerque, New
Mexico 87112. (505) 291-9698. info@Ayurveda.com
<http://www.Ayurveda.com>.
Bastyr University of Natural Health Sciences. 144 N.E. 54th
Street, Seattle, WA 98105. (206) 523-9585.

GALE ENCYCLOPEDIA OF MEDICINE

Center for Mind/Body Medicine. P.O. Box 1048, La Jolla,
CA 92038. (619)794-2425.
College of Maharishi Ayur-Ved, Maharishi International
University. 1000 4th Street, Fairfield, IA 52557. (515)
472-7000.
National Institute of Ayurvedic Medicine. (914) 278-8700.
drgerson@erols.com. <http://www.niam.com>.
Rocky Mountain Institute of Yoga and Ayurveda. P.O. Box
1091, Boulder, CO 80306. (303) 443-6923.
OTHER

‘‘Inside Ayurveda: An Independent Journal of Ayurvedic
Health Care.’’ P.O. Box 3021, Quincy, CA 95971.
<http://www.insideayurveda.com>.

Douglas Dupler, MA

Azithromycin see Erythromycins
AZT see Antiretroviral drugs

477

Ayurvedic medicine

Resources

B
B-cell count see Lymphocyte typing

I Babesiosis
Definition
Babesiosis is an infection of red blood cells caused
by the single-celled parasite, Babesia microti, which is
spread to humans by a tick bite.

Description
Babesiosis is a rare, tick-transmitted disease that
is caused most often by the single-celled parasite
Babesia microti. By 1995, fewer than 500 cases of
babesiosis had been reported in the United States.
The disease occurs primarily in New England and
New York, especially on the coastal islands.
However, cases have occurred in other parts of the
United States. Because of tick activity, the risk for
babesiosis is highest during June and July.
Ticks are small, blood-sucking arachnids.
Although some ticks carry diseasecausing organisms,
most do not. Babesia microti is spread to humans
through the bite of the tick Ixodes scapularis (also
called Ixodes dammini). Ixodes scapularis, called the
‘‘blacklegged deer tick,’’ usually feeds on deer and
mice. A tick picks up the parasites by feeding on an
infected mouse and then passes them on by biting a
new host, possibly a human. To pass on the parasites,
the tick must be attached to the skin for 36-48 hours.
Once in the bloodstream, Babesia microti enters a red
blood cell, reproduces by cell division, and destroys
the cell, causing anemia. Humans infected with
Babesia microti produce antibodies that can be helpful
in diagnosing the infection.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Babesia microti live and divide within red blood
cells, destroying the cells and causing anemia. The
majority of people who are infected have no visible
symptoms. In those who become ill, symptoms appear
one to six weeks following the tick bite. Because the
ticks are small, many patients have no recollection of a
tick bite. The symptoms are flu-like and include tiredness, loss of appetite, fever, drenching sweats, and
muscle pain. Nausea, vomiting, headache, shaking
chills, blood in the urine, and depression can occur.
Persons who are over 40 years old, have had their
spleen removed (splenectomized), and/or have a serious disease (cancer, AIDS, etc.) are at a greater risk
for severe babesiosis. In severe cases of babesiosis, up
to 85% of the blood cells can be infected. This causes a
serious, possibly fatal, blood deficiency.

Diagnosis
Babesiosis can be diagnosed by examining a blood
sample microscopically and detecting the presence of
Babesia microti within the blood cells. The blood can
also be checked for the presence of antibodies to the
parasite.

Treatment
In serious cases, babesiosis is treated with a
combination of clindamycin (Cleocin) and quinine.
Clindamycin is given by injection and quinine is given
orally three to four times a day for four to seven days.
To reduce the number of parasites in the blood, severely
ill patients have been treated with blood transfusions.

Prognosis
Otherwise healthy patients will recover completely. Babesiosis may last several months without
479

Bacillary angiomatosis

KEY TERMS

KEY TERMS

Anemia—A below normal number of red blood
cells in the bloodstream.
Parasite—An organism that lives upon or within
another organism.

Cat-scratch disease—An infectious disease caused
by bacteria transmitted by the common cat flea that
causes a self-limiting, mild infection in healthy
people.
Kaposi’s sarcoma—A malignant condition that
begins as soft brown or purple lesions on the skin
that occurs most often in men with AIDS.

treatment and is a severe, potentially fatal disease in
splenectomized patients.

Prevention
The only prevention for babesiosis is to minimize
exposure to ticks by staying on trails when walking
through the woods, avoiding tall grasses, wearing long
sleeves and tucking pant legs into socks, wearing insect
repellent, and checking for ticks after an outing.
Remove a tick as soon as possible by grasping the
tick with tweezers and gently pulling. Splenectomized
people should avoid northeastern coastal regions
during the tick season.
Resources
OTHER

Mayo Clinic Online. March 5, 1998. <http://
www.mayohealth.org>.

Belinda Rowland, PhD

Bach flower remedies see Flower remedies

I Bacillary angiomatosis
Definition
A life-threatening but curable infection that
causes an eruption of purple lesions on or under the
skin that resemble Kaposi’s sarcoma. The infection,
which occurs almost exclusively in patients with
AIDS, can be a complication of cat-scratch disease.

Description
Bacillary angiomatosis is a re-emerging bacterial
infection that is identical or closely related to one
which commonly afflicted thousands of soldiers during
World War I. Today, the disease, caused by two versions of the same bacteria, is linked to homeless AIDS
patients and to those afflicted with cat-scratch disease.
480

The infection is rarely seen today in patients who
don’t have HIV. According to the U.S. Centers for
Disease Control and Prevention (CDC), an HIV
patient diagnosed with bacillary angiomatosis is considered to have progressed to full-blown AIDS.

Causes and symptoms
Scientists have recently isolated two varieties of
the Bartonella bacteria as the cause of bacillary angiomatosis: Bartonella (formerly Rochalimaea quintana)
and B. henselae (cause of cat-scratch disease).
B. quintana infection is known popularly as trench
fever, and is the infection associated with body lice that
sickened European troops during World War I. Lice
carry the bacteria, and can transmit the infection to
humans. The incidence of trench fever was believed to
have faded away with the end of World War I. It was
not diagnosed in the United States until 1992, when 10
cases were reported among homeless Seattle men.
The related bacteria B. henselae was first identified several years ago as the cause of cat-scratch fever.
It also can lead to bacillary angiomatosis in AIDS
patients. Bacillary angiomatosis caused by this bacteria is transmitted to AIDS patients from cat fleas.
These two different types of bacteria both cause
bacillary angiomatosis, a disease which is characterized by wildly proliferating blood vessels that form
tumor-like masses in the skin and organs. The nodules
that appear in bacillary angiomatosis are firm and
don’t turn white when pressed. The lesions can occur
anywhere on the body, in numbers ranging from one
to 100. They are rarely found on palms of the hands,
soles of the feet, or in the mouth. As the number of
lesions increase, the patient may develop a high fever,
sweats, chills, poor appetite, vomiting, and weight loss.
If untreated, the infection may be fatal.
In addition to the basic disease process, the two
different types of bacteria cause some slightly different
symptoms. Patients infected with B. henselae also
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
This life-threatening but curable infection is often
misdiagnosed, because it may be mistaken for other
conditions (such as Kaposi’s sarcoma). A blood test
developed in 1992 by the CDC detects antibodies to
the bacteria. It can be confirmed by reviewing symptoms, history and negative tests for other diseases that
cause swollen lymph glands. It isn’t necessary to
biopsy a small sample of the lymph node unless there
is a question of cancer of the lymph node or some
other disease.

Bacteremia

experience blood-filled cysts within the liver and
abnormal liver function, whereas B. quintana patients
may have tumor growths in the bone.

I Bacteremia
Definition
Bacteremia is an invasion of the bloodstream by
bacteria.

Description
Bacteremia occurs when bacteria enter the
bloodstream. This may occur through a wound or
infection, or through a surgical procedure or injection. Bacteremia may cause no symptoms and resolve
without treatment, or it may produce fever and other
symptoms of infection. In some cases, bacteremia
leads to septic shock, a potentially life-threatening
condition.

Treatment
Recent research indicates that antibiotics used to
treat other HIV opportunistic infections can both prevent and treat bacillary angiomatosis. Treatment is
usually given until the lesions disappear, which typically takes three or four weeks. A severely affected
lymph node or blister may have to be drained, and a
heating pad may help swollen, tender lymph glands.
Acetaminophen (Tylenol) may relieve pain, aches, and
fever over 101 8F (38.3 8C).

Prognosis
In most cases, prompt antibiotic treatment in
patients with AIDS cured the infection caused by
either variety of the bacteria, and patients may resume
normal life. Early diagnosis is crucial to a cure.

Prevention
Studies suggest that antibiotics may prevent
the disease. Patients also should be sure to treat cats
for fleas.

Causes and symptoms
Causes
Several types of bacteria live on the surface of the
skin or colonize the moist linings of the urinary tract,
lower digestive tract, and other internal surfaces. These
bacteria are normally harmless as long as they are kept
in check by the body’s natural barriers and the immune
system. People in good health with strong immune
systems rarely develop bacteremia. However, when
bacteria are introduced directly into the circulatory
system, especially in a person who is ill or undergoing
aggressive medical treatment, the immune system may
not be able to cope with the invasion, and symptoms of
bacteremia may develop. For this reason, bacteremia is
most common in people who are already affected by or
being treated for some other medical problem. In addition, medical treatment may bring a person in contact
with new types of bacteria that are more invasive than
those already residing in that person’s body, further
increasing the likelihood of bacterial infection.
Conditions which increase the chances of developing bacteremia include:

Resources


immune suppression, either due to HIV infection or
drug therapy



antibiotic therapy which changes the balance of bacterial types in the body



prolonged or severe illness



alcoholism or other drug abuse



malnutrition



diseases or drug therapy that cause ulcers in the
intestines, e.g. chemotherapy for cancer

PERIODICALS

Koehler, J. E. ‘‘Zoonoses: Cats, Fleas and Bacteria.’’
Journal of the American Medical Association 271 (1994):
531-535.

Carol A. Turkington

Bacillary dysentery see Shigellosis
Bacitracin see Antibiotics, topical
GALE ENCYCLOPEDIA OF MEDICINE

481

Bacteremia

KEY TERMS
Colostomy—Surgical creation of an artificial anus
on the abdominal wall by cutting into the colon and
bringing it up to the surface.
Gastrostomy—Surgical creation of an artificial
opening into the stomach through the abdominal
wall to allow tube feeding.
Jejunostomy—Surgical creation of an opening to
the middle portion of the small intestine (jejunum),
through the abdominal wall.
Septic shock—A life-threatening drop in blood
pressure caused by bacterial infection.

Not all of these symptoms are usually present. In
the elderly, confusion may be the only prominent symptom. Bacteremia may lead to septic shock, whose symptoms include decreased consciousness, rapid heart and
breathing rates and multiple organ failures.

Diagnosis
Bacteremia is diagnosed by culturing the blood
for bacteria. Samples may need to be tested several
times over several hours. Blood analysis may also
reveal an elevated number of white blood cells.
Blood pressure is monitored closely; a decline in
blood pressure may indicate the onset of septic shock.

Treatment
Common immediate causes of bacteremia include:


drainage of an abscess, including an abscessed tooth



urinary tract infection, especially in the presence of a
bladder catheter



decubitus ulcers (pressure sores)



intravenous procedures using unsterilized needles,
including IV drug use



prolonged IV needle placement



use of ostomy tubes, including gastrostomy (surgically
making a new opening into the stomach), jejunostomy
(surgically making an opening from the abdominal
wall into the jejunum), and colostomy (surgically
creating an articifical opening into the colon).

The bacteria most likely to cause bacteremia include
members of the Staphylococcus, Streptococcus,
Pseudomonas, Haemophilus, and Esherichia coli (E. coli)
genera.

Bacteremia may cause no symptoms, but may be
discovered through a blood test for another condition.
In this situation, it may not need to be treated, except
in patients especially at risk for infection, such as those
with heart valve defects or whose immune systems are
suppressed.

Prognosis
Prompt antibiotic therapy usually succeeds in clearing bacteria from the bloodstream. Recurrence may
indicate an undiscovered site of infection. Untreated
bacteria in the blood may spread, causing infection of
the heart (endocarditis or pericarditis) or infection of the
covering of the central nervous system (meningitis).

Prevention



fever over 101 8F (38.3 8C)



chills



malaise

Bacteremia can be prevented by preventing the
infections which often precede it. Good personal
hygiene, especially during viral illness, may reduce the
risk of developing bacterial infection. Treating bacterial
infections quickly and thoroughly can minimize the risk
of spreading infection. During medical procedures, the
burden falls on medical professionals to minimize the
number and duration of invasive procedures, to reduce
patients’ exposure to sources of bacteria when being
treated, and to use scrupulous technique.



abdominal pain

Resources



nausea

OTHER



vomiting



diarrhea

The Merck Page. April 13, 1998. <http://
www.merck.com>.



anxiety



shortness of breath



confusion

Symptoms
Symptoms of bacteremia may include:

482

Richard Robinson

Bacterial meningitis see Meningitis
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Bacterial vaginosis (BV) is a type of vaginal infection in which the normal balance of bacteria in the
vagina is disrupted, allowing the overgrowth of harmful
anaerobic bacteria at the expense of protective bacteria.

Description
BV is the most, common and the most serious type
of vaginal infection in women of childbearing age. As
many as 10 to 26 percent of pregnant women in the
United States have BV; BV has been found in 12 to 25
percent of women in routine clinic populations, and in 32
to 64 percent of women in clinics for sexually transmitted
diseases (STDs). BV is different than vaginal yeast infections and requires different methods of treatment.
In most cases, BV does not have lasting effects on
women. However, there can be risks associated with BV:

Causes and symptoms
Bacteria that dominate the vaginal flora in a BV
infection include Gardnerella vaginalis or Mobiluncus,
although other bacteria, such as Escherichia coli from
the rectum have also been shown to cause the disease.
The overgrowth of these harmful bacteria are at the
expense of the protective bacteria lactobacilli, which
secrete a natural disinfectant, hydrogen peroxide, that
maintains the healthy, normal balance of vaginal
microorganisms. The factors that upset the normal
balance of bacteria in the vagina are not well-understood; however, the following activities or behaviors
that have been associated with BV include:


having a new sex partner or multiple sex partners



stress



douching



using an intrauterine device (IUD) for contraception

BV is not transmitted through toilet seats, bedding, swimming pools, or touching of objects. Women
who have not had sexual intercourse rarely have BV.
However BV is not considered an STD, although it
does appear to act like an STD in women who have sex
with women.
The main symptom of BV is a thin, watery or
foamy, white (milky) or gray vaginal discharge with
an unpleasant, foul, fish-like or musty odor. The odor
is sometimes stronger after a woman has sex, when the
semen mixes with the vaginal secretions. Burning or
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anaerobic bacteria—Bacteria that do not require
oxgyen, found in low concentrations in the normal
vagina
Vaginal discharge—discharge of secretions from the
cervical glands of the vagina; normally clear or white

pain during urination can also be present with BV.
Itching on the outside of the vagina and redness can
also occur, but are seen less frequently. However,
many women with BV do not exhibit any symptoms.

Diagnosis
BV is diagnosed through a examination of the
vagina by a health care provider. A woman who suspects that she may have BV should not douche or use a
feminine hygiene spray before the appointment with
the health care provider. Laboratory tests are conducted on a sample of the vaginal fluid to see if the
bacteria present are those associated with BV. The
health care provider may also check to see if there is
decreased vaginal acidity. Potassium hydroxide, when
added to a vaginal discharge sample, enhances vaginal
odors and allows the health care provider to determine
if the odor is fishy or foul.

Treatment
In a few cases, BV might clear up without treatment. However, all women with symptoms of BV
should be treated to relieve symptoms and to avoid
the development of complications such as pelvic inflammatory disease (PID). In most cases, male partners are
not treated, but female sexual partners should be examined to see if they have BV and require treatment.
BV is treated with prescription antibiotics such as
metronidazole or clindamycin creams or oral metronidazole (both are antibiotics that can also be used by pregnant women, although at different doses). Metronidazole
kills anaerobic bacteria but does not harm the protective
lactobacilli. Drinking alcohol should be avoided when
taking metronidazole, for this medicine can cause severe
nausea and vomiting when combined with alcohol.
For postmenopausal women, in addition to the
use of antibiotics, the health care provider may also
prescribe estrogen suppositories or topical cream to
thicken and lubricate vaginal tissues. Sexual activity
should be avoided during treatment; a condom should
be used if the woman does have sexual intercourse.
483

Bacterial vaginosis

I Bacterial vaginosis

Bacterial vaginosis

The woman should be tested after treatment to ensure
that the infection has been cured.

Alternative treatment

Prevention
Since the development of BV often appears to be
associated with sexual activities, recommended ways
to avoid BV include:

Supplement therapies are available in addition to
the use of prescription medicines to ease recovery.
Herbal therapies
Fresh garlic (Allium sativum) has antibacterial
properties and can be added to a woman’s diet. A
fresh, peeled garlic wrapped in gauze can also be
inserted into the vagina to help treat BV. The insert
should be changed twice daily.
To soothe itching or irritation of the vaginal tissues, a woman can bathe the tissues in an infusion of
fresh chickweed (Stellaria media). The infusion is
made by pouring one cup of boiling water on one to
two teaspoons of the herb, steeping for five minutes,
and allowing the mixture to cool before use.

Other ways to prevent BV include:


discontinuing the use of tampons for six months



practicing good hygiene by wiping from front to
back (away from the vagina) after bowel movements
to avoid spreading bacteria from the rectum to the
vagina



wearing cotton panties and panty-hose with a cotton
crotch and avoiding tight or latex clothing to keep
the vagina cool and dry



avoiding the use of perfumed soaps and feminine
sprays



lowering stress levels



avoiding douching, as douching removes some of the
normal bacteria in the vagina that protects women
from infection



finishing the course of antibiotic treatment, even if
the symptoms are relieved, to prevent reoccurrence
of the disease



routinely being tested for BV during regular gynecological examinations

Prognosis


Pregnant women with BV often have babies of low birth
weight (less than 5.5 pounds) or who are premature



Bacteria that cause BV may also cause pelvic inflammatory disease (PID), an infection of the uterus and
fallopian tubes. The risk of a woman with BV developing PID is higher after the woman undergoes surgical procedures such as a hysterectomy or an
abortion. PID can result in infertility and can also
increase the risk of an ectopic pregnancy



BV may increase the risk of a woman becoming
infected with HIV, the virus that causes AIDS



A woman with BV and HIV is more likely to pass
HIV to her sexual partner



BV increases the chance that a woman will contract
other STDs, such as chlamydia and gonorrhea

Some physicians recommend that all women who
have a hysterectomy or an abortion be treated for BV,
to reduce the risk of developing PID.
Resources
BOOKS



practicing abstinence



delaying having sex for the first time, as younger
people who have sex are more likely to contract BV
and STDs

Icon Health Publications. Bacterial Vaginosis - a Medical
Dictionary, Bibliography, and Annotated Research Guide
to Internet References. San Diego, CA: Icon Health
Publications, 2003.
Parker, James N. and Parker, Philip M., editors. The Official
Patient’s Sourcebook on Vaginitis.San Diego, CA: Icon
Health Publications, 2002.
Parker, James N. and Parker, Philip M., editors. The Official
Patient’s Sourcebook on Bacterial Vaginosis. San Diego,
CA: Icon Health Publications, 2003.
Time-Life Books. Vaginal Problems The Medical Advisor..
Richmond, VA: Time-Life Books, 1996.



limiting the number of sexual partners

PERIODICALS



having a sexual relationship with only one partner
who does not have an STD

BV can be successfully treated with antibiotics.



practicing safer sex, which means using a condom
every time when having sex

484

ORGANIZATIONS

American Social Health Association, P.O. Box 13827,
Research Triangle Park, NC 27709. Telephone: (919)
361-8400; Fax: (919) 361-8425; Web site: http://
www.ashastd.org/.
GALE ENCYCLOPEDIA OF MEDICINE

OTHER

3M National Vaginitis Association.Women’s Guide to
Vaginal Infections.Brochure available for download:
www3.3m.com/pdas-nva/cons_addresources.html

Judith Sims

Bacteroides infection see Anaerobic
infections

I Bad breath
Definition
Bad breath, sometimes called halitosis, is an
unpleasant odor of the breath.

Description
Bad breath is likely to be experienced by most
adults at least occasionally. Bad breath, either real or
imagined, can have a significant impact on a person’s
social and professional life.

Causes and symptoms
Bad breath can be caused by a number of problems. Oral diseases, fermentation of food particles in
the mouth, sinus infections, and unclean dentures can
all contribute to mouth odor. Many non-oral diseases,
such as lung infections, kidney failure, or severe liver
disease, can also cause bad breath, though rarely.
Many people think that bad breath can originate in
the stomach or intestines; this is extremely rare. The
esophagus is usually collapsed and closed, and,
although a belch may carry odor up from the stomach,
the chance of bad breath being caused from air continually escaping from the stomach is remote.
Cigarette smoke can cause bad breath, not only in
the cigarette smoker, but also in one who is constantly
exposed to second-hand smoke.

Diagnosis
The easiest way to determine if one has bad breath
is to ask someone who is trustworthy and discrete.
GALE ENCYCLOPEDIA OF MEDICINE

Bad breath

3M National Vaginitis Association. 3M Center, 275-3W-01,
P.O. Box 33275 Saint Paul, MN 55133-3275. Website:
www3.3m.com/pdas-nva/
National Women’s Health Information Center. U.S.
Department of Health and Human Services. Telephone:
(800) 994-9662: Website: www.4woman.gov

KEY TERMS
Halitosis— The medical term for bad breath.

This is usually not too difficult. Another, more private, method of determining if one has bad breath is to
lick one’s wrist, wait until it dries, then smell the area.
Scraping the rear area of the tongue with a plastic
spoon, then smelling the spoon, is another method
one can use to assess bad breath.

Treatment
The most effective treatment of bad breath is to
treat the cause. Poor oral hygiene can be improved by
regular brushing and flossing, as well as regular dental
checkups. Gentle brushing of the tongue should be
part of daily oral hygiene. In addition to good oral
hygiene, the judicious use of mouthwashes is helpful.
Mouth dryness, experienced at night or during fasting,
or due to certain medications and medical conditions,
can contribute to bad breath. Dryness can be avoided
by drinking adequate amounts of water. Chewing gum
may be beneficial.
As mentioned, some medications, such as some
high blood pressure medications, can cause dry mouth.
If this problem is significant, a medication change, under
the supervision of one’s health care provider, may
improve the dry-mouth condition. Oral or sinus infections, once diagnosed, can be treated medically, usually
with antibiotics. Lung infections and kidney or liver
problems will, of course, need medical treatment.

Alternative treatment
Depending on the cause, a multitude of alternative therapeutic remedies can be used. For example,
sinusitis can be treated with steam inhalation of essential oils and/or herbs.

Prognosis
Most bad breath can be treated successfully with
good oral hygiene and/or medical care. Occasionally,
for patients who feel that these therapies are unsuccessful,
some delusional or obsessive behavior pattern might pertain, and mental health counseling may be appropriate.
Resources
ORGANIZATIONS

American Dental Association. 211 E. Chicago Ave., Chicago,
IL 60611. (312) 440-2500. <http://www.ada.org>.
485

Balance and coordination tests

American Medical Association. 515 N. State St., Chicago, IL
60612. (312) 464-5000. <http://www.ama-assn.org>.

Joseph Knight, PA

I Balance and coordination tests
Definition
Balance is the ability to maintain a position.
Coordination is the capacity to move through a complex
set of movements. Balance and coordination depend on
the interaction of multiple body organs and systems
including the eyes, ears, brain and nervous system, cardiovascular system, and muscles. Tests or examination
of any or all of these organs or systems may be necessary
to determine the causes of loss of balance, dizziness, or
the inability to coordinate movement or activities.

Purpose
Tests of balance and coordination, and the examination of the organs and systems that influence
balance and coordination, can help to identify causes
of dizziness, fainting, falling, or incoordination.

Precautions
Tests for balance and coordination should be conducted in a safe and controlled area where patients will
not experience injury if they become dizzy or fall.

Description
Assessment of balance and coordination can
include discussion of the patient’s medical history and
a complete physical examination including evaluation of
the heart, head, eyes, and ears. A slow pulse or heart
rate, or very low blood pressure may indicate a circulatory system problem, which can cause dizziness or fainting. During the examination, the patient may be asked
to rotate the head from side to side while sitting up or
while lying down with the head and neck extended over
the edge of the examination table. If these tests produce
dizziness or a rapid twitching of the eyeballs (nystagmus), the patient may have a disorder of the inner ear,
which is responsible for maintaining balance.
An examination of the eyes and ears may also give
clues to episodes of dizziness or incoordination. The
patient may be asked to focus on a light or on a distant
point or object, and to look up, down, left, and right
486

A patient sits on a ball, working on his balance. He wears a
belt so that the physical therapist can catch him if he loses
balance. (Custom Medical Stock Photo. Reproduced by
permission.)

moving only the eyes while the eyes are examined.
Problems with vision may, in themselves, contribute
to balance and coordination disturbances, or may
indicate more serious problems of the nervous system
or brain function. Hearing loss, fluid in the inner ear,
or ear infection might indicate the cause of balance
and coordination problems.
Various physical tests may also be used. A patient
may be asked to walk a straight line, stand on one foot,
or touch a finger to the nose to help assess balance.
The patient may be asked to squeeze or push against
the doctor’s hands, to squat down, to bend over, stand
on tiptoes or stand on their heels. Important aspects of
these tests include holding positions for a certain number of seconds, successfully repeating movements a
certain number of times, and repeating the test accurately with eyes closed. The patient’s reflexes may also
be tested. For example, the doctor may tap on the
GALE ENCYCLOPEDIA OF MEDICINE

Meniere’s disease—An abnormality of the inner ear
that causes dizziness, ringing in the ears, and hearing loss.

knees, ankles, and elbows with a small rubber mallet to
test nervous system functioning. These tests may
reveal muscle weakness or nervous system problems
that could contribute to incoordination.

Preparation
No special preparation is required prior to administration of balance and coordination tests. The
patient may be asked to disrobe and put on an examination gown to make it easier for the doctor to
observe muscles and reflex responses.

Aftercare
No special aftercare is generally required, however,
some of the tests may cause episodes of dizziness or
incoordination. Patients may need to use caution in
returning to normal activities if they are experiencing
any symptoms of dizziness, lightheadedness, or weakness.

Risks
These simple tests of balance and coordination are
generally harmless.

Normal results
Under normal conditions, these test will not cause
dizziness, loss of balance, or incoordination.

Abnormal results
The presence of dizziness, lightheadedness, loss of
coordination, unusual eye movements, muscle weakness, or impaired reflexes are abnormal results and
may indicate the problem causing the loss of balance
or incoordination. In some cases, additional testing
may be needed to diagnose the cause of balance or
coordination problems.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Ear Foundation. 1817 Patterson St., Nashville, TN 37203.
(800) 545-4327. <http://www.earfoundation.org>.
Vestibular Disorders Association (VEDA). P.O. Box 4467,
Portland, OR 97208-4467. (800) 837-8428 or (503) 2297705. Fax: (503) 229-8064.

Altha Roberts Edgren

I Balanitis
Definition
Balanitis is an inflammation of the head and foreskin of the penis.

Description
Balanitis generally affects uncircumcised males.
These are men who have a foreskin, which is the
‘‘hood’’ of soft skin that partially covers the head of
the penis. In balanitis, the head and foreskin become
red and inflamed. (In circumcised men, who lack a
foreskin, these symptoms only affect the tip of the
penis.) The condition often occurs due to the fungus
Candida albicans, the same organism that causes vaginal yeast infections in women. Balanitis (which is also
referred to as balanoposthitis) can be caused by a
variety of other fungal or bacterial infections, or may
occur due to a sensitivity reaction to common chemical agents.
Uncircumcised men are more at risk for balanitis
due to the presence of the foreskin. The snug fit of the
foreskin around the top of the penis tends to create a
damp, warm environment that encourages the growth
of microorganisms. Most of the organisms associated
with balanitis are already present on the penis, but in
very small numbers. However, if the area between the
head and foreskin is not cleansed thoroughly on a
regular basis, these organisms can multiply and lead
to infection.
Diabetes can increase the risk of developing the
condition.

Causes and symptoms
Balanitis is usually a result of poor hygiene—for
example, neglecting to bathe for several days. A failure
to properly wash (or rinse) the area between the head and
foreskin can lead to the development of fungal or bacterial infections that cause the condition. In other cases,
balanitis may occur due to an allergic reaction: Some
487

Balanitis

KEY TERMS

Balantidiasis

KEY TERMS
Acidophilus—A bacteria believed to combat yeast
infections.
Circumcision—The surgical removal of the
foreskin.
Urethral stricture—A narrowing of the urethra
(urine tube).

preventing yeast infections–a common cause of balanitis. These remedies include garlic, calendula, and
goldenseal. Eating yogurt that contains acidophilus
may also help to clear up a Candida infection.

Prognosis
Most cases go away quickly once the cause is
identified and treated. However, regular bouts of balanitis can result in urethral stricture.

Prevention
men may be sensitive to chemicals found in harsh soaps,
laundry detergents, or contraceptive creams. Men who
contract a sexually transmitted disease (STD) such as
trichimoniasis may also develop symptoms.
The symptoms of balanitis are limited to the foreskin and head of the penis (in circumcised men, only
the head is affected). These include redness, inflammation, pain, discharge, sore or itchy skin, and difficulty
retracting the foreskin.

Diagnosis
Balanitis is usually diagnosed based on a brief
physical examination. This may be conducted by
your regular health care provider or by a urologist,
the type of doctor who specializes in such disorders.
The doctor may take a sample of the discharge (if any)
to determine the nature of the possible infection. A
urine test may be recommended to evaluate glucose
(sugar) levels in the urine. Balanitis treatment is typically covered by medical insurance.

Treatment
The treatment of balanitis depends on the specific
cause, which can vary from case to case. Antibiotics are
used to treat bacterial infections, while topical antifungals such as clotrimazole can combat balanitis caused by
Candida. If an allergic reaction is causing symptoms, the
goal is to identify the chemical agent responsible.
Ointments or creams may be used to ease skin irritation.
No matter what the cause, it is important to thoroughly clean the penis on a daily basis in order to
alleviate symptoms. If the condition keeps occurring,
or if the inflammation is interfering with urination,
circumcision may be advised.

Alternative treatment
According to practitioners of alternative medicine, certain herbs may be effective in controlling or
488

Proper hygiene is the best way to avoid balanitis.
Circumcision is sometimes performed to prevent
repeated cases.
Resources
BOOKS

Tierney, Lawrence M., et al. Current Medical Diagnosis and
Treatment. McGraw-Hill, 2000.
PERIODICALS

Mayser, P. ‘‘Mycotic infections of the penis.’’ Andrologia 31
Supplement 1 (1999): 13-6.
ORGANIZATIONS

U.S. National Library of Medicine. 8600 Rockville Pike,
Bethesda, MD 20894. (888) 346-3656. <http://
www.nlm.nih.gov>.

Greg Annussek

I Balantidiasis
Definition
Balantidiasis is an infectious disease produced by
a single-celled microorganism (protozoan) called
Balantidium coli that infects the digestive tract. It is
primarily a disease of the tropics, although it is also
found in cooler, temperate climates. Most persons
with balantidiasis do not exhibit any noticeable symptoms (asymptomatic), but a few individuals will
develop diarrhea with blood and mucus and an
inflamed colon (colitis).

Description
Balantidiasis is caused by Balantidium coli, a parasitic protozoan that infects the large intestine. B. coli is
the largest and only protozoan, having cilia or hairlike structures, that is capable of causing disease in
GALE ENCYCLOPEDIA OF MEDICINE

Asymptomatic—Persons who carry a disease and
are usually capable of transmitting the disease but
who do not exhibit symptoms of the disease are
said to be asymptomatic.
Biopsy—The removal of a tissue sample for diagnostic purposes.
Ciliated—Covered with short, hair-like protrusions, like B. coli and certain other protozoa. The
cilia or hairs help the organism to move.
Colitis—An inflammation of the large intestine that
occurs in some cases of balantidiasis. It is marked
by cramping pain and the passing of bloody mucus.
Protozoan—A single-celled, usually microscopic
organism, such as B. coli, that is eukaryotic and,
therefore, different from bacteria (prokaryotic).
Sigmoidoscopy—A procedure in which a thin, flexible, lighted instrument, called a sigmoidoscope, is
used to visually examine the lower part of the large
intestine.

humans. Balantidiasis occurs most commonly in areas
with poor sanitation and in settings where humans live
in close contact with pigs, sheep, or goats.

Most individuals with balantidiasis have no
noticeable symptoms. Even though these individuals
may not feel ill, they are still capable of infecting
others by person-to-person contact or by contaminating food or water with cysts that others may ingest, for
example, by preparing food with unwashed hands.
The most common symptoms of balantidiasis are
chronic diarrhea or severe colitis with abdominal
cramps, pain, and bloody stools. Complications may
include intestinal perforation in which the intestinal
wall becomes torn, but the organisms do not spread to
other parts of the body in the blood stream.

Diagnosis
Diagnosis of balantidiasis, as with other similar
diseases, can be complicated, partly because symptoms may or may not be present. A diagnosis of
balantidiasis may be considered when a patient has
diarrhea combined with a possible history of recent
exposure to amebiasis through travel, contact with
infected persons, or anal intercourse.
Specifically, a diagnosis of balantidiasis is made
by finding B. coli cysts or trophozoites in the patient’s
stools or by finding trophozoites in tissue samples
(biopsy) taken from the large bowel. A diagnostic
blood test has not yet been developed.
Stool examination

Causes and symptoms
Balantidiasis is transmitted primarily by eating food
or drinking water that has been contaminated by human
or animal feces containing B. coli cysts. During its life
cycle, this organism exists in two very different forms: the
infective cyst or capsuled form, which cannot move but
can survive outside the human body because of its thick,
protective covering; and the disease-producing form, the
trophozoite, which although capable of moving, cannot
survive once excreted in the feces and, therefore, cannot
infect others. In the digestive tract, the cysts are transported to the intestine where the walls of the cysts are
broken open by digestive secretions, releasing the mobile
trophozoites. Once released within the intestine, the trophozoites multiply by feeding on intestinal bacteria or by
invading the lining of the large intestine. Within the lining
of the large intestine, the trophozoites secrete a substance
that destroys intestinal tissue and creates sores (ulcers) or
abscesses. Trophozoites eventually form new cysts that
are carried through the digestive tract and excreted in the
feces. Under favorable temperature and humidity conditions, the cysts can survive in soil or water for weeks to
months, ready to begin the cycle again.
GALE ENCYCLOPEDIA OF MEDICINE

This test involves microscopically examining a
stool sample for the presence of cysts and/or trophozoites of B. coli.
Sigmoidoscopy
To take a tissue sample from the large intestine, a
procedure called a sigmoidoscopy is performed.
During a sigmoidoscopy, a thin, flexible instrument
is used to visually examine the intestinal lining and
obtain small tissue specimens.

Treatment
Patients with balantidiasis are treated with prescription medication, typically consisting of a ten day
course of either tetracycline or metronidazole.
Alternative drugs that have proven effective in treating balantidiasis include iodoquinol or paromomycin.

Prognosis
Although somewhat dependent on the patient’s
overall health, in general, the prognosis for most
489

Balantidiasis

KEY TERMS

Balloon valvuloplasty

patients with balantidiasis is good. Severely infected
patients occasionally die as a result of a tear in the
intestinal wall (intestinal perforation) and consequent
loss of blood.

Prevention
There are no immunization procedures or medications that can be taken prior to potential exposure to
prevent balantidiasis. Moreover, people who have had
the disease can become reinfected. Prevention requires
effective personal and community hygiene. Specific
safeguards include the following:


Purification of drinking water. Water can be purified
by filtering, boiling, or treatment with iodine.



Proper food handling. Measures include protecting
food from contamination by flies, cooking food
properly, washing one’s hands after using the bathroom and before cooking or eating, and avoiding
foods that cannot be cooked or peeled when traveling in countries with high rates of balantidiasis.



Careful disposal of human feces.



Monitoring the contacts of balantidiasis patients.
The stools of family members and sexual partners
of infected persons should be tested for the presence
of cysts or trophozoites.

Resources
BOOKS

Goldsmith, Robert S. ‘‘Infectious Diseases: Protozoal &
Helminthic.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Baldness see Alopecia
Balloon angioplasty see Angioplasty

I Balloon valvuloplasty
Definition
Balloon valvuloplasty is a procedure in which a
narrowed heart valve is stretched open using a procedure that does not require open heart surgery.
490

KEY TERMS
Cardiac catheterization—A technique used to
evaluate the heart and fix certain problems.
Catheterization is far less invasive than traditional
surgery.
Stenosis—The narrowing of any valve, especially
one of the heart valves or the opening into the
pulmonary artery from the right ventricle.
Valve—Tissue in the passageways between the
heart’s upper and lower chambers that controls
passage of blood and prevents regurgitation.

Purpose
There are four valves in the heart, which are
located at the exit of each of the four chambers of
the heart. They are called aortic valve, pulmonary
valve, mitral valve, and tricuspid valve. The valves
open and close to regulate the blood flow from one
chamber to the next. They are vital to the efficient
functioning of the heart.
In some people the valves are too narrow (a condition called stenosis). Balloon valvuloplasty is performed on children and adults to improve valve
function and blood flow by enlarging the valve opening. It is a treatment for aortic, mitral, and pulmonary
stenosis. Balloon valvuloplasty has the best results as a
treatment for narrowed pulmonary valves. Results in
treating narrowing of the mitral valve are generally
good. It is more difficult to perform and less successful
in treating narrowing of the aortic valve.

Description
Balloon valvuloplasty is a procedure in which a
thin tube (catheter) that has a small deflated balloon at
the tip is inserted through the skin in the groin area
into a blood vessel, and then is threaded up to the
opening of the narrowed heart valve. The balloon is
inflated, which stretches the valve open. This procedure cures many valve obstructions. It is also called
balloon enlargement of a narrowed heart valve.
The procedure is performed in a cardiac catheterization laboratory and takes up to four hours. The patient is
usually awake, but is given local anesthesia to make the
area where the catheter is inserted numb. After the site
where the catheter will be inserted is prepared and
anesthetized, the cardiologist inserts a catheter into the
appropriate blood vessel, then passes a balloon-tipped
GALE ENCYCLOPEDIA OF MEDICINE

heart rhythms, reduced blood flow, heart attack, heart
puncture, infection, and circulatory problems.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Lori De Milto

Preparation
For at least six hours before balloon valvuloplasty, the patient will have to avoid eating or drinking
anything. An intravenous line is inserted so that medications can be administered. The patient’s groin area
is shaved and cleaned with an antiseptic. About an
hour before the procedure, the patient is given an
oral sedative such as diazepam (Valium).

Aftercare
After balloon valvuloplasty, the patient is sent to
the recovery room for several hours, where he or she is
monitored for vital signs (such as pulse and breathing)
and heart sounds. An electrocardiogram, which is a
record of the electrical impulses in the heart, is done.
The leg in which the catheter was inserted is temporarily prevented from moving. The skin condition is
monitored. The insertion site, which will be covered
by a sandbag, is observed for bleeding until the catheter is removed. Intravenous fluids will be given to help
eliminate the x-ray dye; intravenous blood thinners or
other medications to dilate the coronary arteries may
be given. Pain medication is available.
For at least 30 minutes after removal of the catheter, direct pressure is applied to the site of insertion; after
this a pressure dressing will be applied. Following discharge from the hospital, the patient can usually resume
normal activities. After balloon valvuloplasty lifelong
follow-up is necessary because valves sometimes degenerate or narrowing recurs, making surgery necessary.

Risks
Balloon valvuloplasty can have serious complications. For example, the valve can become misshapen so
that it doesn’t close completely, which makes the condition worse. Embolism, where pieces of the valve break off
and travel to the brain or the lungs, is another possible
risk. If the procedure causes severe damage to the valve
leaflets, immediate surgery is required. Less frequent
complications are bleeding and hematoma (a local collection of clotted blood) at the puncture site, abnormal
GALE ENCYCLOPEDIA OF MEDICINE

Bancroftian filariasis see Elephantiasis
Bang’s disease see Brucellosis

I Barbiturate-induced coma
Definition
A barbiturate-induced coma, or barb coma, is a
temporary state of unconsciousness brought on by a
controlled dose of a barbiturate drug, usually pentobarbital or thiopental.

Purpose
Barbiturate comas are used to protect the brain
during major brain surgery, such as the removal of
arteriovenous malformations or aneurysms. Coma may
also be induced to control intracranial hypertension
caused by brain injury.

Precautions
Barbiturate-induced comas are used when conventional therapy to reduce intracranial hypertension
has failed. Barbiturate dosing is geared toward burst
suppression–that is, reducing brain activity as measured by electroencephalography. This reduction in
brain activity has to be balanced against the potential
side effects of barbiturates, which include allergic reactions and effects on the cardiovascular system.

Description
One of the greatest hazards associated with brain
injury is intracranial hypertension. Brain injury may be
caused by an accidental head injury or a medical condition, such as stroke, tumor, or infection. When the
brain is injured, fluids accumulate in the brain, causing
it to swell. The skull does not allow for the expansion of
the brain; in effect, the brain becomes compressed.
491

Barbiturate-induced coma

catheter through the first catheter. Guided by a video
monitor and an x ray, the physician slowly threads the
catheter into the heart. The deflated balloon is positioned in the valve opening, then is inflated repeatedly.
The inflated balloon widens the valve’s opening by splitting the valve leaflets apart. Once the valve is widened,
the balloon-tipped catheter is removed. The other catheter remains in place for 6 to 12 hours because in some
cases the procedure must be repeated.

Barbiturates

KEY TERMS
Aneurysm—A bulge or sack-like projection from a
blood vessel.
Arteriovenous malformation—An abnormal tangle
of arteries and veins in which the arteries feed
directly into the veins without a normal intervening
capillary bed.
Diuretic agent—A drug which increases urine
output.
Electroencephalography—The recording of electrical potentials produced by the brain. These
potentials indicate brain activity.
Hyperventilation—A respiratory therapy involving
deeper and/or faster breathing to keep the carbon
dioxide pressure in the blood below normal.
Intracranial hypertension—Abnormally high
blood pressure within the skull.
Osmotherapy—Intravenous injection or oral
administration of an agent that induces dehydration. The goal of dehydration is to reduce the
amount of accumulated fluid in the brain.
Steroid—A type of drug used to reduce swelling.

If the pressure does not abate, oxygenated blood
may not reach all areas of the brain. Also, the brain
tissue may be forced against hard, bony edges on the
interior of the skull. In either case, the brain tissue may
die, causing permanent brain damage or death.

failed. Before coma is induced, intracranial hypertension may be treated by hyperventilation; by
facilitation of blood flow from the brain; by
decompressive surgical procedures, such as draining
excess fluids from under the skull or from the
chambers within the brain (ventricles); or by drug
therapy, including osmotherapy, diuretic agents, or
steroids.

Risks
An estimated 25% of barbiturate-induced
comas are accompanied by severe side effects. The
side effects of barbiturates, especially the depressive effect on the cardiovascular system, can be too
risky for some patients. Other side effects include
impaired gastrointestinal motility and impaired
immune response and infection. Since barbiturates
depress activity in the brain, measurements of
brain activity may be unreliable. Careful monitoring of the patient is required to ensure nutritional
needs are being met and to guard against complications, such as lung infection, fevers, or deep vein
blood clots.

Normal results
In many patients who do not respond to conventional therapy, barbiturate-induced coma can
achieve the necessary control of intracranial
hypertension.
Resources
PERIODICALS

Barbiturates reduce the metabolic rate of brain
tissue, as well as the cerebral blood flow. With these
reductions, the blood vessels in the brain narrow,
decreasing the amount of swelling in the brain. With
the swelling relieved, the pressure decreases and some
or all brain damage may be averted.

Schwab, Stefan, et al. ‘‘Barbiturate Coma in Severe
Hemispheric Stroke: Useful or Obsolete?’’ Neurology 48
(1997): 1608.

Controversy exists, however, over the benefits of
using barbiturates to control intracranial hypertension. Some studies have shown that barbiturateinduced coma can reduce intracranial hypertension
but does not necessarily prevent brain damage.
Furthermore, the reduction in intracranial hypertension may not be sustained.

Barbiturate withdrawal see Withdrawal
syndromes

Preparation
Inducing a barbiturate coma is usually kept in
reserve for cases in which conventional treatments
for controlling intracranial hypertension have
492

Julia Barrett

I Barbiturates
Definition
Barbiturates are medicines that act on the central
nervous system and cause drowsiness and can control
seizures.
GALE ENCYCLOPEDIA OF MEDICINE

Barbiturates are in the group of medicines known
as central nervous system depressants (CNS). Also
known as sedative-hypnotic drugs, barbiturates make
people very relaxed, calm, and sleepy. These drugs are
sometimes used to help patients relax before surgery.
Some may also be used to control seizures (convulsions). Although barbiturates have been used to treat
nervousness and sleep problems, they have generally
been replaced by other medicines for these purposes.
These medicines may become habit forming and
should not be used to relieve everyday anxiety and
tension or to treat sleeplessness over long periods.

Description
Barbiturates are available only with a physician’s
prescription and are sold in capsule, tablet, liquid,
and injectable forms. Some commonly used barbiturates are phenobarbital (Barbita) and secobarbital
(Seconal).

Recommended dosage
Recommended dosage depends on the type of
barbiturate and other factors such as the patient’s
age and the condition for which the medicine is being
taken. Check with the physician who prescribed the
drug or the pharmacist who filled the prescription for
the correct dosage.
Always take barbiturates exactly as directed.
Never take larger or more frequent doses, and do
not take the drug for longer than directed. If the
medicine does not seem to be working, even after
taking it for several weeks, do not increase the
dosage. Instead, check with the physician who prescribed the medicine.
Do not stop taking this medicine suddenly without first checking with the physician who prescribed it.
It may be necessary to taper down gradually to reduce
the chance of withdrawal symptoms. If it is necessary
to stop taking the drug, check with the physician for
instructions on how to stop.

Precautions
See a physician regularly while taking barbiturates. The physician will check to make sure the medicine is working as it should and will note unwanted
side effects.
Because barbiturates work on the central nervous
system, they may add to the effects of alcohol and
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Adrenal glands—Two glands located next to the
kidneys. The adrenal glands produce the hormones
epinephrine and norepinephrine and the corticosteroid (cortisone-like) hormones.
Anemia—A lack of hemoglobin – the compound in
blood that carries oxygen from the lungs throughout the body and brings waste carbon dioxide from
the cells to the lungs, where it is released.
Central nervous system—The brain and spinal
cord.
Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Hypnotic—A medicine that causes sleep.
Porphyria—A disorder in which porphyrins build
up in the blood and urine.
Porphyrin—A type of pigment found in living
things, such as chlorophyll, that makes plants
green and hemoglobin which makes blood red.
Sedative—Medicine that has a calming effect and
may be used to treat nervousness or restlessness.
Seizure—A sudden attack, spasm, or convulsion.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug to which he or she has
become dependent.

other drugs that slow the central nervous system,
such as antihistamines, cold medicine, allergy medicine, sleep aids, medicine for seizures, tranquilizers,
some pain relievers, and muscle relaxants. They may
also add to the effects of anesthetics, including those
used for dental procedures. The combined effects of
barbiturates and alcohol or other CNS depressants
(drugs that slow the central nervous system) can be
very dangerous, leading to unconsciousness or even
death. Anyone taking barbiturates should not drink
alcohol and should check with his or her physician
before taking any medicines classified as CNS
depressants.
Taking an overdose of barbiturates or combining
barbiturates with alcohol or other central nervous
system depressants can cause unconsciousness and
even death. Anyone who shows signs of an overdose
or a reaction to combining barbiturates with alcohol
493

Barbiturates

Purpose

Barbiturates

or other drugs should get emergency medical help
immediately. Signs include:


severe drowsiness



breathing problems



slurred speech



staggering



slow heartbeat



severe confusion



severe weakness

Barbiturates may change the results of certain
medical tests. Before having medical tests, anyone
taking this medicine should alert the health care professional in charge.
People may feel drowsy, dizzy, lightheaded, or
less alert when using these drugs. These effects may
even occur the morning after taking a barbiturate
at bedtime. Because of these possible effects, anyone who takes these drugs should not drive, use
machines or do anything else that might be dangerous until they have found out how the drugs
affect them.
Barbiturates may cause physical or mental dependence when taken over long periods. Anyone who
shows these signs of dependence should check with
his or her physician right away:


the need to take larger and larger doses of the medicine to get the same effect

physician know before taking the drugs again. The
physician should also be told about any allergies to
foods, dyes, preservatives, or other substances.
PREGNANCY. Taking barbiturates during pregnancy increases the chance of birth defects and may
cause other problems such as prolonged labor and
withdrawal effects in the baby after birth. Pregnant
women who must take barbiturates for serious or lifethreatening conditions should thoroughly discuss with
their physicians the benefits and risks of taking this
medicine.
BREASTFEEDING. Barbiturates pass into breast
milk and may cause problems such as drowsiness,
breathing problems, or slow heartbeat in nursing
babies whose mothers take the medicine. Women
who are breastfeeding should check with their physicians before using barbiturates.
OTHER MEDICAL CONDITIONS. Before using barbiturates, people with any of these medical problems
should make sure their physicians are aware of their
conditions:


alcohol or drug abuse



depression



hyperactivity (in children)



pain



kidney disease



liver disease



a strong desire to keep taking the medicine



diabetes



withdrawal symptoms, such as anxiety, nausea or
vomiting, convulsions, trembling, or sleep problems,
when the medicine is stopped



overactive thyroid



underactive adrenal gland



chronic lung diseases such as asthma or emphysema



severe anemia



porphyria

Children may be especially sensitive to barbiturates. This may increase the chance of side effects such
as unusual excitement.
Older people may also be more sensitive that
others to the effects of this medicine. In older people,
barbiturates may be more likely to cause confusion,
depression, and unusual excitement. These effects are
also more likely in people who are very ill.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take barbiturates. Before taking these drugs, be
sure to let the physician know about any of these
conditions:
ALLERGIES. Anyone who has had unusual reactions to barbiturates in the past should let his or her

494

USE OF CERTAIN MEDICINES. Taking barbiturates
with certain other drugs may affect the way the drugs
work or may increase the chance of side effects.

Side effects
The most common side effects are dizziness, lightheadedness, drowsiness, and clumsiness or unsteadiness.
These problems usually go away as the body adjusts to
the drug and do not require medical treatment unless
they persist or interfere with normal activities.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with the physician who prescribed the medicine
immediately:
GALE ENCYCLOPEDIA OF MEDICINE

Other central nervous system (CNS) depressants
such as medicine for allergies, colds, hay fever, and
asthma; sedatives; tranquilizers; prescription pain
medicine; muscle relaxants; medicine for seizures;
sleep aids; barbiturates; and anesthetics.

wheezing



Blood thinners.

skin problems, such as rash, hives, or red, thickened,
or scaly skin



Adrenocorticoids (cortisone-like medicines).



Antiseizure medicines such as valproic acid (Depakote
and Depakene), and carbamazepine (Tegretol).

fever



muscle or joint pain



sore throat



chest pain or tightness in the chest






bleeding sores on the lips



sores or painful white spots in the mouth



swollen eyelids, face, or lips

In addition, check with a physician as soon as
possible if confusion, depression, or unusual excitement occur after taking barbiturates.
Patients who take barbiturates for a long time or
at high doses may notice side effects for some time
after they stop taking the drug. These effects usually
appear within 8-16 hours after the patient stops taking
the medicine. Check with a physician if these or other
troublesome symptoms occur after stopping treatment
with barbiturates:

The list above does not include every drug that
may interact with barbiturates. Be sure to check with
a physician or pharmacist before combining barbiturates with any other prescription or nonprescription
(over-the-counter) medicine.
Resources
PERIODICALS

Miller, Norman S. ‘‘Sedative-Hypnotics: Pharmacology and
Use.’’ Journal of Family Practice 29 (December 1989):
665.

Nancy Ross-Flanigan



dizziness, lightheadedness or faintness



anxiety or restlessness



hallucinations



vision problems

I Bariatric surgery



nausea and vomiting

Definition



seizures (convulsions)



muscle twitches or trembling hands



weakness



sleep problems, nightmares, or increased dreaming

Other side effects may occur. Anyone who has
unusual symptoms during or after treatment with barbiturates should get in touch with his or her physician.

Interactions
Birth control pills may not work properly when
taken while barbiturates are being taken. To prevent
pregnancy, use additional or additional methods of
birth control while taking barbiturates.
Barbiturates may also interact with other medicines.
When this happens, the effects of one or both of the drugs
may change or the risk of side effects may be greater.
Anyone who takes barbiturates should let the physician
know all other medicines he or she is taking. Among the
drugs that may interact with barbiturates are:
GALE ENCYCLOPEDIA OF MEDICINE

Bariatric surgery promotes weight loss by changing the digestive system’s anatomy, limiting the
amount of food that can be eaten and digested.

Purpose
Obesity normally is defined through the use of
body mass index (BMI) measurement. Physician
offices, obesity associations, nutritionists, and others
offer methods for calculating BMI, which is a comparison of height to weight. Those with a BMI of 30 or
higher are considered obese. However, at 40 or higher,
they are considered severely obese—approximately
about 100 pounds overweight for men and 80 pounds
overweight for women.
Many people who are obese struggle to lose
weight through diet and exercise but fail. Only after
they have tried other methods of losing weight will
they be candidates for bariatric surgery, which today
is considered a ‘‘last resort’’ for weight loss. In general,
guidelines agree that those with a BMI of 40 or more,
or a BMI of 35 to 39.9 and a serious obesity-related
495

Bariatric surgery





Bariatric surgery

KEY TERMS
Digestive tract—The organs that perform digestion, or changing of food into a form that can be
absorbed by the body. They are the esophagus,
stomach, small intestine, and large instestine.
Esophagus—A muscular tube about nine inches
long that carries food from the throat (pharynx) to
the stomach.

health problem, qualify for bariatric surgery. More
than 23 million Americans are candidates for bariatric
surgery. More than 100,000 of the procedures were
performed in 2003 and the number of surgeries performed will probably continue to rise for many years.

Precautions
Bariatric surgery is not for everyone and the
surgeon and other physicians will evaluate all medical conditions before allowing a patient to proceed. As a major surgery, there are associated
risks and side effects. Women of childbearing age
should be aware that rapid weight loss and nutritional deficiency associated with bariatric surgery
may be harmful to a developing fetus. It is important that a patient reveal all current medications
and conditions during any pre-operative discussions or examinations. Also, the physician will
carefully evaluate the patient to ensure that he or
she is prepared to make a lifelong commitment to
the changes in eating and lifestyle required to make
the surgery successful.
Though many studies have shown general safety
associated with the major surgeries, they are relatively
new and research on long-term effects are not as widespread as they are for many other surgeries and procedures. When choosing a surgeon to perform the
operation, patients should check with organizations
such as the American Society for Bariatric Surgery
for certification. A patient also should ask about the
surgeon’s experience in performing the particular
operation.
Although the number of obese teenagers and
resulting bariatric surgeries has increased, some
experts are questioning the decision to perform
bariatric surgery on teens. There are no specific clinical guidelines for determining a safe age for the
procedure, but some physicians agree that bariatric
surgery is not appropriate for children younger than
496

age 15, since they are still growing and forming
bones.

Description
When food is chewed and swallowed, it moves
along the digestive tract. In the stomach, a strong
acid helps break down food so it can be digested
and the body can absorb the food’s nutrients and
calories. The stomach can hold about three pints
of food at one time. As digestion continues, food
particles become smaller and move from the stomach
into the intestine. The various parts of the small
intestine are nearly 20 feet long if laid out straight.
Those food particles not digested in the small intestine are stored in the large intestine until they are
eliminated as waste.
When a patient has bariatric surgery, this digestive process is altered to help the patient lose weight.
There are three main types of bariatric surgery, but
only two types are commonly used today. The types
are restrictive, malabsorptive, and combined restrictive/malabsorptive.
Restrictive surgery, often referred to as ‘‘stomach stapling’’ uses bands or staples to create a
small pouch at the top of the stomach where food
enters from the esophagus. This smaller pouch may
hold only about 1 ounce of food at first and may
stretch to hold about 2-3 ounces. The pouch’s
lower opening is made small, so that food moves
slowly to the lower part of the stomach, adding to
the feeling of fullness. The most frequently performed types of restrictive surgeries are vertical
banded gastroplasty (VBG), gastric banding, and
laparoscopic gastric banding. VBG is used less
today in favor of gastric banding, which involves
an adjustable hollow band made of silicone rubber.
Laparoscopic gastric banding, or Lap-band, was
approved by the U.S. Food and Drug Administration
(FDA) in 2001. Sometimes referred to as ‘‘minimally
invasive’’ bariatric surgery, the surgeon uses small
incisions and a laparoscope, or a small, tubular instrument with a camera attached, to see inside the abdomen and apply the band.
Malabsorptive procedures help patients lose
weight by limiting the amount of nutrients and calories the intestine can absorb. Sometimes called intestinal bypasses, they are no longer used in the United
States because they have often resulted in severe nutritional deficiencies.
Combined restrictive/malabsorptive operations
are the most common bariatric surgeries. They work
GALE ENCYCLOPEDIA OF MEDICINE

is important for bariatric surgery patients to lose
weight at the recommended pace, take nutritional supplements as recommended, and attend follow-up visits
with physicians and nutritionists.

Procedure times vary, depending on the type of
bariatric surgery chosen. However, most patients are
in surgery for about one to two hours. Though costs
can be as high as $35,000, more insurance companies
are beginning to pay for the procedures if they are
proven medically necessary. In 2004, the agency that
pays for Medicare costs recognized obesity and many
of its treatments as a medical cost for the first time,
recognizing that obesity leads to many other medical
problems.

The surgeon performing the procedure should
discuss its specific risks prior to surgery. Risks for
bariatric surgery include infection, blood clots, abdominal hernia, gallstones, nutritional deficiencies, possible nerve complications, and death. Death rates have
been reported lowest for RGB and VBG, at less than
1% of patients.

Preparation
The physician will first make sure that a patient is
mentally prepared for the surgery and the commitment to follow-up care that will be required. Patients
should have a consultation appointment with the
surgeon prior to the procedure to discuss risks and
benefits. Pre-operative instructions will be given that
will tell the patient specific preparations prior to the
surgery. These may include instructions about avoiding food or liquids, certain medications, and other
instructions on the day before or the day of the procedure. Patients also may have several laboratory or
other diagnostic tests prior to the surgery.

Aftercare
Depending on the type of procedure and any possible complications, patients can expect to stay at the
hospital or surgery center for about two to four days
following the surgery. Those who have laparoscopic
operations typically have shorter hospital stays and
speedier recovery times. The physician and nurses will
provide instructions for wound care and other followup when the patient is discharged from the hospital.
Usually, bariatric surgery patients can resume normal
activity within about six weeks following surgery, and
as little as two weeks after laparoscopic procedures. It
GALE ENCYCLOPEDIA OF MEDICINE

How a patient complies with instructions from
physicians following bariatric surgery is important.
Most patients will require lifelong use of nutritional
supplements such as multivitamins, calcium, and other
vitamin supplements to prevent nutritional deficiencies. Because the stomach is smaller, patients will have
to eat small portions of food and often must avoid
certain types of food such as sugar.

Risks

Normal results
Weight loss will occur gradually, as patients can
eat less food and absorb fewer calories. When patients
follow post-operative instructions, they can lead normal lives, eating less food and being careful to limit
certain foods that may irritate their new stomach
pouches. Most patients will lose 50–60% of their
excess weight in the first year or two. With gastric
bypass surgery, many can lose up to two-thirds of
excess weight by the second postoperative year.
Resources
PERIODICALS

‘‘Gastric Bypass Patients Should Recognize Risk of Nerve
Injury Post-surgery.’’ Life Science Weekly (Nov. 2,
2004):973.
MacNeil, Jane Saladoff. ‘‘Gastric Bypass Beat Medical Care
for Moderate Obesity.’’ Family Practice News (Jan. 15,
2005):60–61.
Santora, Marc. ‘‘Teenagers Turn to Surgery to Shrink Their
Stomachs.’’ The New York Times (Nov. 26, 2004):B1.
ORGANIZATION

American Obesity Association. 1250 12th St. NW, Suite 300,
Washington, DC 20037. 202-776-7711. http://
www.obesity.org.
Society of American Gastrointestinal Endoscopic Surgeons.
11300 West Olympic Blvd., Suuite 600, Los Angeles,
CA 90064. 310-437-0544. http://www.sages.org.

497

Bariatric surgery

by restricting both the amount of food the stomach
can hold and the amount of calories and nutrients the
body absorbs. The most common and successful combined surgery in recent years is called the Roux-en-Y
gastric bypass (RGB). In this operation, the surgeon
first creates a small pouch at the top of the stomach.
Next, a Y-shaped section of the small intestine is connected to the small pouch, allowing food to bypass the
lower stomach, the first part of the small intestine
(duodenum), and the first portion of the next section
of the small intestine ( jejunum). It connects into the
second half of the jejunum, reducing the amount of
calories and nutrients the body absorbs. RGB may be
performed with a laparoscope and a series of tiny
incisions or with a large abdominal incision.

Barium enema

OTHER

Gastrointestinal Surgery for Severe Obesity Weight-control
Information Network, National Institutes of Health,
2004. http://win.niddk.nih.gov/publications/
gastric.htm.

Teresa G. Odle

I Barium enema
Definition
A barium enema, also known as a lower GI (gastrointestinal) exam, is a test that uses x-ray examination to view the large intestine. There are two types of
this test: the single-contrast technique where barium
sulfate is injected into the rectum in order to gain a
profile view of the large intestine; and the doublecontrast (or ‘‘air contrast’’) technique where air is
inserted into the rectum.

KEY TERMS
Barium sulfate—A barium compound used during
a barium enema to block the passage of x rays
during the exam.
Bowel lumen—The space within the intestine.
Colonoscopy—An examination of the upper portion of the rectum performed with a colonoscope or
elongated speculum.
Diverticula—A diverticulum of the colon is a sac or
pouch in the colon walls which is usually asymptomatic (without symptoms) but may cause difficulty
if it becomes inflamed.
Diverticulitis—A condition of the diverticulum of
the intestinal tract, especially in the colon, where
inflammation may cause distended sacs extending
from the colon and pain.
Ulcerative colitis— An ulceration or erosion of the
mucosa of the colon.
Proctosigmoidoscopy—A visual examination of the
rectum and sigmoid colon using a sigmoidoscope.

Purpose
A barium enema may be performed for a variety of
reasons, including to aid in the diagnosis of colon and
rectal cancer (or colorectal cancer), and inflammatory
disease. Detection of polyps (a benign growth in the
tissue lining of the colon and rectum), diverticula (a
pouch pushing out from the colon), and structural
changes in the large intestine can also be established with
this test. The double-contrast barium enema is the best
method for detecting small tumors (such as polyps), early
inflammatory disease, and bleeding caused by ulcers.
The decision to perform a barium enema is based
on a person’s history of altered bowel habits. These
can include diarrhea, constipation, any lower abdominal pain they are currently exhibiting, blood, mucus,
or pus in their stools. It is also recommended that this
exam be used every five to 10 years to screen healthy
people for colorectal cancer, the second most deadly
type of tumor in the United States. Those who have
a close relative with colorectal cancer or have had
a precancerous polyp are considered to be at an
increased risk for the disease and should be screened
more frequently to look for abnormalities.

Precautions
While barium enema is an effective screening
method in the detection of symptoms and may lead
to a timely diagnosis of several diseases, it is not the
498

only method to do this. As of 1997, some studies have
shown that the colonoscopy procedure performed by
experienced gastroenterologists is a more accurate
initial diagnostic tool for detecting early signs of colorectal cancer. A colonoscopy is the most accurate way
for the physician to examine the entire colon and
rectum for polyps. If abnormalities are seen at this
time the procedure is accompanied by a biopsy.
Some physicians use sigmoidoscopy plus a barium
enema instead of colonoscopy.

Description
To begin a barium enema, the patient will lie with
their back down on a tilting radiographic table in order
to have x rays of the abdomen taken. After being
assisted to a different position, a well-lubricated rectal
tube is inserted through the anus. This tube allows the
physician or assistant to slowly administer the barium
into the intestine. While this filling process is closely
monitored, it is important for the patient to keep the
anus tightly contracted against the rectal tube to help
maintain its position and prevent the barium from
leaking. This step is emphasized to the patient due to
the inaccuracy that may be caused if the barium leaks.
A rectal balloon may also be inflated to help retain the
barium. The table may be tilted or the patient moved to
a different position to aid in the filling process.
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
In order to conduct the most accurate barium
enema test, the patient must follow a prescribed diet
and bowel preparation instructions prior to the test.
This preparation commonly includes restricted intake
of diary products and a liquid diet for 24 hours prior to
the test, in addition to drinking large amounts of water
or clear liquids 12–24 hours before the test. Patients
may also be given laxatives, and asked to give themselves a cleansing enema.
In addition to the prescribed diet and bowel preparation prior to the test, the patient can expect the
following during a barium enema:


They will be well draped with a gown as they are
secured to a tilting x-ray table.



As the barium or air is injected into the intestine, they
may experience cramping pains or the urge to defecate.



The patient will be instructed to take slow, deep
breaths through the mouth to ease any discomfort.

Aftercare
Patients should follow several steps immediately
after undergoing a barium enema, including:


Drink plenty of fluids to help counteract the dehydrating effects of bowel preparation and the test.



Take time to rest. A barium enema and the bowel
preparation taken before it can be exhausting.



A cleansing enema may be given to eliminate any
remaining barium. Lightly colored stools will be prevalent for the next 24–72 hours following the test.

Risks
While a barium enema is considered a safe screening
test used on a routine basis, it can cause complications in
certain people. The following indications should be kept
in mind before a barium enema is performed:
GALE ENCYCLOPEDIA OF MEDICINE



Those who have a rapid heart rate, severe ulcerative
colitis, toxic megacolon, or a presumed perforation
in the intestine should not undergo a barium enema.



The test can be cautiously performed if the patient
has a blocked intestine, ulcerative colitis, diverticulitis, or severe bloody diarrhea.



Complications that may be caused by the test include
perforation of the colon, water intoxication, barium
granulomas (inflamed nodules), and allergic reaction. These are all very rare.

Normal results
When the patient undergoes a single-contrast
enema, their intestine is steadily filled with barium
to differentiate the colon’s markings. A normal result
displays uniform filling of the colon. As the barium is
expelled, the intestinal walls collapse. A normal result
on the x ray after defecation will show the intestinal
lining as having a standard, feathery appearance.
Accordingly, the double-contrast enema expands
the intestine which is already lined with a thin layer of
barium, but with air to display a detailed image of the
mucosal pattern. Varying positions taken by the
patient allow the barium to collect on the dependent
walls of the intestine by way of gravity.

Abnormal results
A barium enema allows abnormalities to appear on
an x ray that may aid in the diagnosis of several different
conditions. Although most colon cancers occur in the
rectosigmoid region, or upper part of the rectum and
adjoining portion of the sigmoid colon, and are better
detected with a different test called a proctosigmoidoscopy, an enema can identify other early signs of cancer.
Identification of polyps, diverticulosis, inflammatory disease, such as diverticulitis and ulcerative colitis
is attainable through a barium x ray. Structural
changes in the intestine, gastroenteritis, and some
cases of acute appendicitis may also be apparent by
viewing this x ray.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta, GA
30329-4251. (800) 227-2345. <http://www.cancer.org>.

Beth A. Kapes

Barium swallow see Upper GI exam
Barlow’s syndrome see Mitral valve prolapse
499

Barium enema

As the barium fills the intestine, x rays of the abdomen are taken to distinguish significant findings.There
are many ways to perform a barium enema. One way is
that shortly after filling, the rectal tube is removed and
the patient expels as much of the barium as possible.
Upon completing this, an additional x ray is taken, and
a double-contrast enema may follow. If this is done
immediately, a thin film of barium will remain in the
intestine, and air is then slowly injected to expand the
bowel lumen. Sometimes no x rays will be taken until
after the air is injected.

Bartholin’s gland cyst

I Bartholin’s gland cyst

KEY TERMS

Definition

Marsupialization—Cutting out a wedge of the cyst
wall and putting in stitches so the cyst cannot reoccur.
Sitz bath—A warm bath in which just the buttocks
and genital area soak in water; used to reduce pain
and aid healing in the genital area.

A Bartholin’s gland cyst is a swollen fluid-filled
lump that develops from a blockage of one of the
Bartholin’s glands, which are small glands located on
each side of the opening to the vagina. Bartholin’s
gland cysts and abscesses are commonly found in
women of reproductive age, developing in approximately 2% of all women.

Window operation—Cutting out a large ovalshaped piece of the cyst wall and putting in stitches
to create a window so the cyst cannot reoccur.
Word catheter—A small rubber catheter with an
inflatable balloon tip that is inserted into a stab
incision in the cyst, after the contents of the cyst
have been drained.

Description
The Bartholin’s glands are located in the lips of the
labia that cover the vaginal opening. The glands (normally the size of a pea) provide moisture for the vulva
area. A Bartholin’s gland cyst may form in the gland itself
or in the duct draining the gland. A cyst normally does
not cause pain, grows slowly, and may go away without treatment. It usually ranges in size from 0.4-1.2 in.
(1–3 cm), although some may grow much larger.
If infected, a Bartholin’s gland cyst can form an
abscess that will increase in size over several days and
is very painful. In order to heal, a Bartholin’s gland
cyst usually must be drained.

normally occurring in the vagina. Over 60 types of
bacteria have been found in Bartholin’s gland abscesses.

Diagnosis
A Bartholin’s gland cyst or abscess is diagnosed
by a gynecological pelvic exam. If the cyst appears to
be infected, a culture is often performed to identify the
type of bacteria causing the abscess.

Causes and symptoms

Treatment

A Bartholin’s gland cyst occurs if the duct
becomes blocked for any reason, such as infection,
injury, or chronic inflammation. Very rarely a cyst is
caused by cancer, which usually occurs only in women
over the age of 40. In many cases, the cause of a
Bartholin’s gland cyst is unknown.

Treatment for this condition depends on the size
of the cyst, whether it is painful, and whether the cyst is
infected.

Symptoms of an uninfected Bartholin’s gland cyst
include a painless jump on one side of the vulva area
(most common symptom) and redness or swelling in
the vulva area.



watchful waiting by the woman and her health care
professional



soaking of the genital area with warm towel
compresses



soaking of the genital area in a sitz bath



use of non-prescription pain medication to relieve
mild discomfort

Symptoms of an abscessed Bartholin’s gland
include:

If the cyst is not infected, treatment options
include:



pain that occurs with walking, sitting, physical activity, or sexual intercourse



fever and chills

If the Bartholin’s gland is infected, there are several
treatments available to treat the abscess, including:



increased swelling in the vulva area over a two- to
four-day period



soaking of the genital area in a sitz bath

drainage from the cyst, normally occurring four to
five days after the swelling starts





treatment with antibiotics



use of prescription or non-prescription pain medication



incision and drainage, i.e., cutting into the cyst and
draining the fluid (not usually successful, as the cyst
often reoccurs)

Abscesses may be caused by sexually transmitted
bacteria, such as those causing chlamydial or gonococcal infections, while others are caused by bacteria
500

GALE ENCYCLOPEDIA OF MEDICINE

placement of a drain (Word catheter) in the cyst for
two to four weeks so fluid can drain and prevent
reoccurrence of the cyst



marsupialization



window operation



use of a carbon dioxide laser to open the cyst and
heat the cyst wall tissue so that the cyst cannot form a
sac and reoccur



incision and drainage, followed by treatment with
silver nitrate to burn the cyst wall so the cyst cannot
form a sac and reoccur



removal of the entire Bartholin’s gland cyst, if the
cyst has reoccurred several times after use of other
treatment methods

During surgical treatment, the area will be numbed
with a local anesthetic to reduce pain. General anesthesia may be used for treatment of an abscess, as the
procedure can be painful.
In a pregnant woman, surgical treatment of cysts
that are asymptomatic should be delayed until after
delivery to avoid the possibility of excessive bleeding.
However, if the Bartholin’s gland is infected and must
be drained, antibiotics and local anesthesia are generally considered safe.
If the cyst is caused by cancer, the gland must be
excised, and the woman should be under the care of a
gynecologist familiar with the treatment of this type of
cancer.

Alternative treatment
If a Bartholin’s gland cyst has no or mild symptoms, or has opened on its own to drain, a woman may
decide to use watchful waiting, warm sitz baths, and
non-prescription pain medication. If symptoms
become worse or do not improve, a health care professional should then be consulted.
Infected Bartholin’s glands should be evaluated
and treated by a health care professional.

Prognosis
A Bartholin’s gland cyst should respond to treatment in a few days. If an abscess requires surgery,
healing may take days to weeks, depending on the
size of the abscess and the type of surgical procedure
used. Most of the surgical procedures, except for incision and drainage, should be effective in preventing
recurring infections.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
There are few ways to prevent the formation of
Bartholin’s gland cysts or abscesses. However, as a
Bartholin’s gland abscess may be caused by a sexually
transmitted disease, the practice of safe sex is recommended. Using good hygiene, i.e., wiping front to back
after a bowel movement, is also recommended to prevent bacteria from the bowels from contaminating the
vaginal area.
Resources
BOOKS

Toth, P. P. ‘‘Management of Bartholin’s Gland Duct Cysts
and Abscesses.’’ In Saunders Manual of Medical
Practice. Philadelphia: W.B. Saunders, 2000.

Judith Sims

Bartonella bacilliformis infection see
Bartonellosis

I Bartonellosis
Definition
Bartonellosis is an infectious bacterial disease
with an acute form (which has a sudden onset and
short course) and a chronic form (which has more
gradual onset and longer duration). The disease is
transmitted by sandflies and occurs in western South
America. Characterized by a form of red blood cell
deficiency (hemolytic anemia) and fever, the potentially fatal acute form is called Oroya fever or
Carrion’s disease. The chronic form is identified by
painful skin lesions.

Description
The acute form of the disease gets its name from an
outbreak that occurred in 1871 near La Oroya, Peru.
More than 7,000 people perished. Some survivors later
developed a skin disease, called verruga peruana
(Peruvian warts). These skin lesions were observed
prior to the 1871 outbreak–perhaps as far back as the
pre-Columbian era–but a connection to Oroya fever
was unknown. In 1885, a young medical researcher,
Daniel Carrion, inoculated himself with blood from a
lesion to study the course of the skin disease. When he
became ill with Oroya fever, the connection became
apparent. Oroya fever is often called Carrion’s disease
in honor of his fatal experiment.
501

Bartonellosis



Bartonellosis

KEY TERMS
Acute—Referring to the course of a disease, or
a phase of a disease, the short-term experience of
prominent symptoms.
Chronic—Referring to the course of a disease, or
a phase of a disease, the long-term experience of
prominent symptoms.
Erythrocytes—Red blood cells.
Hemolytic anemia—A form of erythrocyte deficiency
caused by the destruction of the red blood cells.
Host—The organism that harbors or nourishes
another organism (parasite). In bartonellosis, the
person infected with Bartonella basilliformis.
Vector—An organism, such as insects or rodents,
that can transmit disease to humans.

The bacteria, Bartonella bacilliformis, was isolated
by Alberto Barton in 1909, but wasn’t identified as the
cause of the fever until 1940. The Bartonella genus
includes at least 11 bacteria species, four of which
cause human diseases, including cat-scratch disease
and bacillary angiomatosis. However, bartonellosis
refers exclusively to the disease caused by B. bacilliformis. The disease is limited to a small area of the Andes
Mountains in western South America; nearly all cases
have been in Peru, Colombia, and Ecuador. A large
outbreak involving thousands of people occurred in
1940–41, but bartonellosis has since occurred sporadically. Control of sandflies, the only known disease carrier
(vector), has been credited with managing the disease.

Causes and symptoms
Bartonellosis is transmitted by the nocturnal
sandfly and arises from infection with B. bacilliformis.
The sandfly, Lutzomyia verrucarum, dines on human
blood and, in so doing, can inject bacteria into the
bloodstream. The sandfly is found only in certain
areas of the Peruvian Andes; other, as-yet-unidentified
vectors are suspected in Ecuador and Colombia.

individuals may exhibit the characteristic lesions without ever experiencing the acute phase. Left untreated,
the lesions may last months or years. These lesions
resemble blood-filled blisters, up to 1.6 in (4 cm) in
diameter, and appear primarily on the head and limbs.
They can be painful to the touch and may bleed or
ulcerate.

Diagnosis
Bartonellosis is identified by symptoms and the
patient’s history, such as recent travel in areas where
bartonellosis occurs. Isolation of B. bacilliformis from
the bloodstream or lesions can confirm the diagnosis.

Treatment
Antibiotics are the mainstay of bartonellosis treatment. The bacteria are susceptible to several antibiotics,
including chloramphenicol, penicillins, and aminoglycosides. Blood transfusions may be necessary to treat the
anemia caused by bartonellosis.

Prognosis
Antibiotics have dramatically decreased the fatality associated with bartonellosis. Prior to the development of antibiotics, the fever was fatal in 40% of cases.
With antibiotic treatment, that rate has dropped to
8%. Fatalities can result from complications associated
with severe anemia and secondary infections. Once
the infection is halted, an individual can recover fully.

Prevention
Avoiding sandfly bites is the primary means of
prevention. Sandfly eradication programs have been
helpful in decreasing the sandfly population, and insect
repellant can be effective in preventing sandfly bites.
Resources
BOOKS

Daly, Jennifer S. ‘‘Bartonella Species.’’ In Infectious
Diseases, edited by Sherwood F. Gorbach, John S.
Bartlett, and Neil R. Blacklow, 2nd ed. Philadelphia:
W. B. Saunders Co., 1998.

Once in the bloodstream, the bacteria latch onto
red blood cells (erythrocytes), burrow into the cells,
and reproduce. In the process, up to 90% of the host’s
erythrocytes are destroyed, causing severe hemolytic
anemia. The anemia is accompanied by high fever,
muscle and joint pain, delirium, and possibly coma.

Basal cell cancer see Skin cancer,
non-melanoma

Two to eight weeks after the acute phase, an
infected individual develops verruga peruana. However,

Basal gastric secretion test see Gastric acid
determination

502

Julia Barrett

GALE ENCYCLOPEDIA OF MEDICINE

Definition
Battered child syndrome refers to injuries sustained by a child as a result of physical abuse, usually
inflicted by an adult caregiver. Alternative terms
include: shaken baby; shaken baby syndrome; child
abuse; and non-accidental trauma (NAT).

Description
Internal injuries, cuts, burns, bruises and broken or
fractured bones are all possible signs of battered child
syndrome. Emotional damage to a child is also often
the by-product of child abuse, which can result in serious
behavioral problems such as substance abuse or the
physical abuse of others. Approximately 14% of children in the United States are physically abused each
year, and an estimated 2,000 of those children die as a
result of the abuse. Between 1994-1995, 1.1 million cases
of child abuse were recorded in the United States; of that
number, 55% of the victims were less than a year old.

Causes and symptoms
Battered child syndrome (BCS) is found at every
level of society, although the incidence may be higher
in low-income households where adult caregivers suffer greater stress and social difficulties, without having
had the benefit of higher education. The child abuser
most often injures a child in the heat of anger, and was
often abused as a child himself. The incessant crying of
an infant or child may trigger abuse. Symptoms may
include a delayed visit to the emergency room with an
injured child; an implausible explanation of the cause
of a child’s injury; bruises that match the shape of a
hand, fist or belt; cigarette burns; scald marks; bite
marks; black eyes; unconsciousness; bruises around
the neck; and a bulging fontanel in infants.

Diagnosis
Battered child syndrome is most often diagnosed
by an emergency room physician or pediatrician, or by
teachers or social workers. Physical examination will
detect bruises, burns, swelling, retinal hemorrhages.
X rays, and other imaging techniques, such as MRI
or scans may confirm fractures or other internal injuries. The presence of injuries at different stages of
healing (i.e. having occurred at different times) is
nearly always indicative of BCS. Establishing the diagnosis is often hindered by the excessive cautiousness
of caregivers or by actual concealment of the true
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Fontanel—Soft spot on top of an infant’s skull.
Subdural hematoma—Bleeding over the brain.
Multiple retinal hemorrhages—Bleeding in the
back of the eye.

origin of the childþs injuries, as a result of fear,
shame and avoidance or denial mechanisms.

Treatment
Medical treatment for battered child syndrome
will vary according to the type of injury incurred.
Counseling and the implementation of an intervention
plan for the child’s parents or guardians is necessary.
The child abuser may be incarcerated, and/or the
abused child removed from the home to prevent
further harm. Reporting child abuse to authorities is
mandatory for doctors, teachers, and childcare workers in most states as a way to prevent continued abuse.
Both physical and psychological therapy are often
recommended as treatment for the abused child.

Prognosis
The prognosis for battered child syndrome will
depend on the severity of injury, actions taken by the
authorities to ensure the future safety of the injured
child, and the willingness of parents or guardians to
seek counseling for themselves as well as for the child.

Prevention
Recognizing the potential for child abuse in a situation, and the seeking or offering of intervention and
counseling before battered child syndrome occurs is the
best way to prevent it. Signs that physical abuse may be
forthcoming include parental alcohol or substance
abuse; previous abuse of the child or the child’s siblings;
history of mental or emotional problems in parents;
parents abused as children; absence of visible parental
love or concern for the child; child’s hygiene neglected.
Resources
BOOKS

Lukefahr, James L. Treatment of Child Abuse.Baltimore,
MD: Johns Hopkins University Press, 2000.
PERIODICALS

Mulryan, Kathleen, ‘‘Protecting the Child.’’ Nursing (July
2000).
503

Battered child syndrome

I Battered child syndrome

Bed-wetting

ORGANIZATIONS

Childhelp National Abuse Hotline. (800)422-4453.

Mary Jane Tenerelli, MS

Becker muscular dystrophy see Muscular
dystrophy
Beclomethasone see Corticosteroids

I Bed-wetting
Definition
Bed-wetting is the unintentional (involuntary) discharge of urine during the night. Although most children between the ages of three and five begin to stay
dry at night, the age at which children are physically
and emotionally ready to maintain complete bladder
control varies. Enuresis is a technical term that refers
to the continued, usually involuntary, passage of urine
during the night or the day after the age at which
control is expected.

Description
Most children wet the bed occasionally, and definitions of the age and frequency at which bed-wetting
becomes a medical problem vary somewhat. Many
researchers consider bed-wetting normal until age 6.
About 10% of 6-year-old children wet the bed about
once a month. More boys than girls have this problem.
The American Psychiatric Association, however,
defines enuresis as repeated voiding of urine into the
bed or clothes at age five or older. The wetting is usually
involuntary but in some cases it is intentional. For a
diagnosis of enuresis, wetting must occur twice a week
for at least three months with no underlying physiological cause. Enuresis, both nighttime (nocturnal) and
daytime (diurnal), at age five affects 7% of boys and
3% of girls. By age 10, it affects 3% of boys and 2% of
girls; only 1% of adolescents experience enuresis.
Enuresis is divided into two classes. A child with
primary enuresis has never established bladder control. A child with secondary enuresis begins to wet
after a prolonged dry period. Some children have
both nocturnal and diurnal enuresis.

Causes and symptoms
The causes of bed-wetting are not entirely known.
It tends to run in families. Most children with primary
504

KEY TERMS
Acupressure—A technique using pressure to various points on the body to alleviate health problems.
ADH—Antidiuretic hormone, or the hormone that
helps to concentrate urine during the night.
Behavior modification—Techniques used to
change harmful behavior patterns.
Bladder—The muscular sac or container that stores
urine until it is released from the body through the
tube that carries urine from the bladder to the outside of the body (urethra).
DDAVP—Desmopressin acetate, a drug used to
regulate urine production.
Hypnosis—The technique by which a trained professional relaxes the subject and then asks questions or gives suggestions.
Imipramine hydrochloride—A drug used to
increase bladder capacity.
Kidneys—A pair of organs located on each side of
the spine in the lower back area. They excrete, or
get rid of, urine.
Nocturnal enuresis—Involuntary discharge of
urine during the night.
Urinalysis—A urine test.
Urine—The fluid excreted by the kidneys, stored in
the bladder, then discharged from the body through
the tube that carries urine from the bladder to the
outside of the body (urethra).
Void—To empty the bladder.

enuresis have a close relative–a parent, aunt, or uncle–
who also had the disorder. About 70% of children
with two parents who wet the bed will also wet the
bed. Twin studies have shown that both of a pair of
identical twins experience enuresis more often than
both of a pair of fraternal twins.
Sometimes bed-wetting can be caused by a serious
medical problem like diabetes, sickle-cell anemia, or
epilepsy. Snoring and episodes of interrupted breathing during sleep (sleep apnea) occasionally contribute
to bed-wetting problems. Enlarged adenoids can cause
these conditions. Other physiological problems, such
as urinary tract infection, severe constipation, or spinal
cord injury, can cause bed-wetting.
Children who wet the bed frequently may have a
smaller than normal functional bladder capacity.
Functional bladder capacity is the amount of urine a
GALE ENCYCLOPEDIA OF MEDICINE

Parents often report that their bed-wetting child is
an extremely sound sleeper and difficult to wake.
However, several research studies found that bedwetting children have normal sleep patterns and that
bed-wetting can occur in any stage of sleep.
Recent medical research has found that many
children who wet the bed may have a deficiency of
an important hormone known as antidiuretic hormone (ADH). ADH helps to concentrate urine during
sleep hours, meaning that the urine contains less
water and therefore takes up less space. This decreased
volume of water usually prevents the child’s bladder
from overfilling during the night, unless the child
drank a lot just before going to bed. Testing of
many bed-wetting children has shown that these
children do not have the usual increase in ADH during sleep. Children who wet the bed, therefore, often
produce more urine during the hours of sleep than
their bladders can hold. If they do not wake up, the
bladder releases the excess urine and the child wets
the bed.
Research demonstrates that in most cases bedwetting does not indicate that the child has a physical
or psychological problem. Children who wet the bed
usually have normal-sized bladders and have sleep
patterns that are no different from those of non-bedwetting children. Sometimes emotional stress, such as
the birth of a sibling, a death in the family, or separation from the family, may be associated with the onset
of bed-wetting in a previously toilet-trained child.
Daytime wetting, however, may indicate that the problem has a physical cause.
While most children have no long-term problems
as a result of bed-wetting, some children may develop
psychological problems. Low self-esteem may occur
when these children, who already feel embarrassed,
are further humiliated by angry or frustrated parents
who punish them or who are overly aggressive about
toilet training. The problem can by aggravated when
playmates tease or when social activities such as sleepaway camp are avoided for fear of teasing.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
If a child continues to wet the bed after the age of
six, parents may feel the need to seek evaluation and
diagnosis by the family doctor or a children’s specialist (pediatrician). Typically, before the doctor can
make a diagnosis, a thorough medical history is
obtained. Then the child receives a physical examination, appropriate laboratory tests, including a urine
test (urinalysis), and, if necessary, radiologic studies
(such as x rays).
If the child is healthy and no physical problem is
found, which is the case 90% of the time, the doctor
may not recommend treatment but rather may provide the parents and the child with reassurance, information, and advice.

Treatment
Occasionally a doctor will determine that the problem is serious enough to require treatment. Standard
treatments for bed-wetting include bladder training
exercises, motivational therapy, drug therapy, psychotherapy, and diet therapy.
Bladder training exercises are based on the theory
that those who wet the bed have small functional
bladder capacity. Children are told to drink a large
quantity of water and to try to prolong the periods
between urinations. These exercises are designed to
increase bladder capacity but are only successful in
resolving bed-wetting in a small number of patients.
In motivational therapy, parents attempt to
encourage the child to combat bed-wetting, but the
child must want to achieve success. Positive reinforcement, such as praise or rewards for staying dry, can
help improve self-image and resolve the condition.
Punishment for ‘‘wet’’ nights will hamper the child’s
self-esteem and compound the problem.
The following motivational techniques are commonly used:


Behavior modification. This method of therapy is
aimed at helping children take responsibility for their
nighttime bladder control by teaching new behaviors.
For example, children are taught to use the bathroom
before bedtime and to avoid drinking fluids after
dinner. While behavior modification generally produces good results, it is long-term treatment.



Alarms. This form of therapy uses a sensor placed
in the child’s pajamas or in a bed pad. This sensor
triggers an alarm that wakes the child at the first sign
of wetness. If the child is awakened, he or she can then
go to the bathroom and finish urinating. The intention
505

Bed-wetting

person can hold in the bladder before feeling a strong
urge to urinate. When functional capacity is small, the
bladder will not hold all the urine produced during the
night. Tests have shown that bladder size in these
children is normal. Nevertheless, they experience frequent strong urges to urinate. Such children urinate
often during the daytime and may wet several times at
night. Although a small functional bladder capacity
may be caused by a developmental delay, it may also
be that the child’s habit of voiding frequently slows
bladder development.

Bed-wetting

is to condition a response to awaken when the bladder
is full. Bed-wetting alarms require the motivation
of both parents and children. They are considered
the most effective form of treatment now available.

Common homeopathic remedies used in this treatment
include Causticum, Lycopodium, and Pulsatilla.

A number of drugs are also used to treat bedwetting. These medications are usually fast acting;
children often respond to them within the first week
of treatment. Among the drugs commonly used are a
nasal spray of desmopressin acetate (DDAVP), a substance similar to the hormone that helps regulate urine
production; and imipramine hydrochloride, a drug
that helps to increase bladder capacity. Studies show
that imipramine is effective for as many as 50% of
patients. However, children often wet the bed again
after the drug is discontinued, and it has some side
effects. Some bed-wetting with an underlying physical
cause can be treated by surgical procedures. These
causes include enlarged adenoids that cause sleep
apnea, physical defects in the urinary system, or a
spinal tumor.

Hypnosis is another approach that is being used
successfully by practitioners trained in this therapy. It
trains the child to awaken and go to the bathroom
when his or her bladder feels full. Hypnosis is less
expensive, less time-consuming, and less dangerous
than most approaches; it has virtually no side effects.
Recent medical studies show that hypnotherapy can
work quickly–within four to six sessions.

Psychotherapy is indicated when the child exhibits
signs of severe emotional distress in response to events
such as a death in the family, the birth of a new child, a
change in schools, or divorce. Psychotherapy is also
indicated if a child shows signs of persistently low selfesteem or depression.
In rare cases, allergies or intolerances to certain
foods–such as dairy products, citrus products, or chocolate–can cause bed-wetting. When children have food
sensitivities, bed-wetting may be helped by discovering
the substances that trigger the allergic response and
eliminating these substances from the child’s diet.

Hypnosis

Prognosis
Occasional bed-wetting is not a disease and it does
not have a ‘‘cure.’’ If the child has no underlying
physical or psychological problem that is causing the
bed-wetting, in most cases he or she will outgrow the
condition without treatment. About 15% of bedwetters
become dry each year after age 6. If bed-wetting is
frequent, accompanied by daytime wetting, or falls
into the American Psychiatric Association’s diagnostic
definition of enuresis, a doctor should be consulted. If
treatment is indicated, it usually successfully resolves
the problem. Marked improvement is seen in about
75% of cases treated with wetness alarms.

Prevention
Although preventing a child from wetting the bed
is not always possible, parents can take steps to help
the child keep the bed dry at night. These steps include:


Encouraging and praising the child for staying dry
instead of punishing when the child wets.



Reminding the child to urinate before going to bed, if
he or she feels the need.



Limiting liquid intake at least two hours before
bedtime.

Alternative treatment
A number of alternative treatments are available
for bed-wetting.
Massage
According to practitioners of this technique, pressure applied to various points on the body may help
alleviate the condition. Acupressure or massage, when
done by a trained therapist, may also be helpful in bedwetting caused by a neurologic problem.
Herbal and homeopathic remedies
Some herbal remedies, such as horsetail (Equisetum
arvense) have also been used to treat bed-wetting. A
trained homeopathic practitioner, working at the constitutional level, will seek to rebalance the child’s vital force,
eliminating the imbalanced behavior of bed-wetting.
506

Resources
ORGANIZATIONS

Association for the Care of Children’s Health (ACCH). 7910
Woodmont Ave., Suite 300, Bethesda, MD 20814. (800)
808-2224.
National Association for Continence. P.O. Box 8310,
Spartenburg, SC 29305. (800) 252-3337. <http://
www.nafc.org>.
National Enuresis Society. 7777 Forest Lane, Suite C-737,
Dallas, TX 75230-2518. (800) 697-8080. <http://
www.peds.umn.edu/Centers/NES>.

Genevieve Slomski, Ph.D.
GALE ENCYCLOPEDIA OF MEDICINE

Bedsores

I Bedsores
Definition
Bedsores are also called decubitus ulcers, pressure
ulcers, or pressure sores. These tender or inflamed
patches develop when skin covering a weight-bearing
part of the body is squeezed between bone and another
body part, or a bed, chair, splint, or other hard object.

Description
Each year, about one million people in the
United States develop bedsores ranging from mild
inflammation to deep wounds that involve muscle
and bone. This often painful condition usually starts
with shiny red skin that quickly blisters and deteriorates into open sores that can harbor life-threatening
infection.
Bedsores are not cancerous or contagious. They
are most likely to occur in people who must use wheelchairs or who are confined to bed. In 1992, the federal
Agency for Health Care Policy and Research reported
that bedsores afflict:

Bedsore. (Photograph by Michael English, M.D., Custom Medical
Stock Photo. Reproduced by permission.)



heart problems



incontinence (inability to control bladder or bowel
movements)



malnutrition



obesity



paralysis or immobility



10% of hospital patients



poor circulation



25% of nursing home residents





60% of quadriplegics

prolonged bed rest, especially in unsanitary conditions or with wet or wrinkled sheets



spinal cord injury

The Agency also noted that 65% of elderly people
hospitalized with broken hips develop bedsores and
that doctors fees for treatment of bedsores amounted
to $2,900 per person.
Bedsores are most apt to develop on the:


ankles



back of the head



heels



hips



knees



lower back



shoulder blades



spine

People over the age of 60 are more likely than
younger people to develop bedsores. Risk is also
increased by:

Causes and symptoms
Bedsores most often develop when constant pressure pinches tiny blood vessels that deliver oxygen and
nutrients to the skin. When skin is deprived of oxygen
and nutrients for as little as an hour, areas of tissue can
die and bedsores can form.
Slight rubbing or friction against the skin can
cause minor pressure ulcers. They can also develop
when a patient stretches or bends blood vessels by
slipping into a different position in a bed or chair.
Urine, feces, or other moisture increases the risk
of skin infection, and people who are unable to move
or recognize internal cues to shift position have a
greater than average risk of developing bedsores.
Other risk factors include:


malnutrition



anemia (lack of red blood cells)



atherosclerosis (hardening of arteries)



diabetes or other conditions that make skin more
susceptible to infection



diuse atrophy (muscle loss or weakness from lack of
use)



diminished sensation or lack of feeling



infection

GALE ENCYCLOPEDIA OF MEDICINE

507

Bedsores

Diagnosis
Bedsores usually follow six stages:


redness of skin



redness, swelling, and possible peeling of outer layer
of skin



dead skin, draining wound, and exposed layer of fat



tissue death through skin and fat, to muscle



inner fat and muscle death



destruction of bone, bone, infection, fracture, and
blood infection

Treatment
Prompt medical attention can prevent surface
pressure sores from deepening into more serious infections. For mild bedsores, treatment involves relieving
pressure, keeping the wound clean and moist, and
keeping the area around the ulcer clean and dry.
Antiseptics, harsh soaps, and other skin cleansers can
damage new tissue, so a saline solution should be used
to cleanse the wound whenever a fresh non-stick dressing is applied.
The patient’s doctor may prescribe infectionfighting antibiotics, special dressings or drying agents,
or lotions or ointments to be applied to the wound in a
thin film three or four times a day. Warm whirlpool
treatments are sometimes recommended for sores on
the arm, hand, foot, or leg.
In a procedure called debriding, a scalpel may be
used to remove dead tissue or other debris from the
wound. Deep, ulcerated sores that don’t respond to
other therapy may require skin grafts or plastic surgery.
A doctor should be notified whenever a person:

vitamins or minerals should never be used without a
doctor’s approval.
A poultice made of equal parts of powdered slippery elm (Ulmus fulva), marsh mallow (Althaea officinalis), and echinacea (Echinacea spp.) blended with a small
amount of hot water can relieve minor inflammation.
An infection-fighting rinse can be made by diluting two
drops of essential tea tree oil (Melaleuca spp.) in eight
ounces of water. An herbal tea made from the calendula
(Calendula officinalis) can act as an antiseptic and
wound healing agent. Calendula cream can also be used.
Contrasting hot and cold local applications can
increase circulation to the area and help flush out
waste products, speeding the healing process. The temperatures should be extreme (hot hot and ice cold), yet
tolerable to the skin. Hot compresses should be applied
for three minutes, followed by 30 seconds of cold compress application, repeating the cycle three times. The
cycle should always end with the cold compress.

Prevention
It is usually possible to prevent bedsores from
developing or worsening. The patient should be
inspected regularly; should bathe or shower every
day, using warm water and mild soap; and should
avoid cold or dry air. A bedridden patient should be
repositioned at least once every two hours while
awake. A person who uses a wheelchair should shift
his weight every 10 or 15 minutes, or be helped to
reposition himself at least once an hour. It is important to lift, rather than drag, a person being repositioned. Bony parts of the body should not be
massaged. Even slight friction can remove the top
layer of skin and damage blood vessels beneath it.



will be bedridden or immobilized for an extended time

If the patient is bedridden, sensitive body parts
can be protected by:



is very weak or unable to move



sheepskin pads



develops bedsores



special cushions placed on top of a mattress



a water-filled mattress



a variable-pressure mattress whose sections can be
individually inflated or deflated to redistribute
pressure.

Immediate medical attention is required whenever:


skin turns black or becomes inflamed, tender, swollen, or warm to the touch.



the patient develops a fever during treatment.



the sore contains pus or has a foul-smelling discharge.

With proper treatment, bedsores should begin to
heal two to four weeks after treatment begins.

Alternative treatment
Zinc and vitamins A, C, E, and B complex help
skin repair injuries and stay healthy, but large doses of
508

Pillows or foam wedges can prevent a bedridden
patient’s ankles from irritating each other, and pillows
placed under the legs from mid-calf to ankle can raise
the heels off the bed. Raising the head of the bed
slightly and briefly can provide relief, but raising the
head of the bed more than 30 degrees can cause the
patient to slide, thereby causing damage to skin and
tiny blood vessels.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Bedsores can usually be cured, but about 60,000
deaths a year are attributed to complications caused
by bedsores. Bedsores can be slow to heal. Without
proper treatment, they can lead to:


gangrene (tissue death)



osteomyelitis (infection of the bone beneath the
bedsore)



sepsis (tissue-destroying bacterial infection)



other localized or systemic infections that slow the
healing process, increase the cost of treatment,
lengthen hospital or nursing home stays, or cause
death

Resources

Description
Behcet’s syndrome is a chronic disease that
involves multiple body systems. The disease is named
for a Turkish dermatologist, Hulusi Behcet, who first
reported a patient with recurrent mouth and genital
ulcers along with uveitis in 1937. The disease occurs
worldwide, but is most prevalent in Japan, the Middle
East, and in the Mediterranean region. There is a
wider prevalence among males than females in a
ratio of two to one.

Causes and symptoms
The cause of Behcet’s syndrome is unknown.
Symptoms include recurring ulcers in the mouth or
the genital area, skin lesions, arthritis that affects
mainly the knees and ankles, pain and irritation in
the eyes, and fever. The mouth and genital ulcers tend
to occur in multiples and can be quite painful. In the
mouth, these ulcers are generally found on the tongue, gums, and the inside of the lips or jaws. In the
genital area, the ulcers usually occur on the penis and
scrotum in males and on the vulva of women. The eye
inflammation can lead to blindness.

ORGANIZATIONS

International Association of Enterstomal Therapy. 27241
La Paz Road, Suite 121, Laguna Niguel, CA 92656.
(714) 476-0268.
National Pressure Ulcer Advisory Panel. SUNY at Buffalo,
Beck Hall, 3435 Main St., Buffalo, NY 14214. (716)
881-3558. <http://www.npuap.org>.

Maureen Haggerty

Beef tapeworm infection see Tapeworm
diseases
Behavior therapy see Cognitive-behavioral
therapy

I Behcet’s syndrome
Definition
A group of symptoms that affect a variety of body
systems, including musculoskeletal, gastrointestinal,
and the central nervous system. These symptoms
include ulceration of the mouth or the genital area,
skin lesions, and inflammation of the uvea (an area
around the pupil of the eye).
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Because Behcet’s syndrome is a multisystem disease, it is difficult to diagnose. International criteria
have been proposed to assist in classifying this disease.
There is no one diagnostic feature of this disease, so
diagnosis depends on grouping together enough
symptoms in order to identify the disease. Symptoms
of Behcet’s syndrome also occur in other diseases, so it
is often necessary to rule out the other diseases before
a definitive diagnosis can be reached.

Treatment
Some of the current drugs used to treat Behcet’s
syndrome include corticosteroids, cyclosporine,
azathioprine, chlorambucil, interferon alpha, thalidomide, levamisole and pulse cyclophosphamide.

Prognosis
The prognosis for Behcet’s syndrome is generally
poor. There has been a documented case of Behcet’s
lasting for 17 years. Although the disease is considered
painful but not fatal, when the central nervous system is
involved there is usually severe disability and death
often occurs. The condition is usually chronic, although
there can be remissions during the course of the disease.
There is no predictable method to determine which
509

Behcet’s syndrome

A person who uses a wheelchair should be encouraged to sit up as straight as possible. Pillows behind
the head and between the legs can help prevent bedsores, as can a special cushion placed on the chair seat.
Donut-shaped cushions should not be used because
they restrict blood flow and cause tissues to swell.

Bejel

KEY TERMS
Remission—When active symptoms of a chronic
disease are absent.
Uveitis—Inflammation of the area of the eye
around the pupil.

patients will progress into the more serious symptoms,
and which might move into remission.

syphilis, endemic syphilis is not a sexually transmitted disease.

Description
Bejel has many other names depending on the
locality: siti, dichuchwa, njovera, belesh, and skerljevo
are some of the names. It is most commonly found in
the Middle East (Syria, Saudi Arabia, Iraq), Africa,
central Asia, and Australia. Bejel is related to yaws
and pinta, but has different symptoms.

Causes and symptoms

Prevention
There is no known prevention for Behcet’s
syndrome.
Resources
BOOKS

Ruddy, Shaun. Kelley’s Textbook of Rheumatology.
Philadelphia: W.B. Saunders Company, 2001.
Tierney, Lawrence, et al. Current Medical Diagnosis and
Treatment. Los Altos: Lange Medical Publications, 2001.
PERIODICALS

Okada, A. A. ‘‘Drug Therapy in Behcet’s Disease.’’
OcularImmunology and Inflammation June 2000: 85-91.
Shed, L. P. ‘‘Thalomide Responsiveness in an Infant with
Behcet’s Syndrome.’’ Pediatrics June 1999: 1295-1297.
ORGANIZATIONS

American Behcet’s Disease Association. P.O. Box 280240,
Memphis, TN 38168-0240. <http://
www.behcets.com>.
Behcet’s Organization Worldwide, Head Office. P.O. Box
27, Watchet, Somerset TA23 OYJ, United Kingdom.
<http://www.behcets.org>.
National Eye Institute. National Institute of Health. Bldg. 31,
Rm. 6A32, Bethesda, MD 30892-2510. (800) 869-2020.
2020@nei.nih.gov. <http://www.nei.nih.gov>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseaes.org>.

Kim A. Sharp, M.Ln.

I Bejel

Treponema pallidum, the bacteria that causes
bejel, is very closely related to the one that causes the
sexually transmitted form of syphilis, but transmission
is very different. In bejel, transmission is by direct
contact, with broken skin or contaminated hands, or
indirectly by sharing drinking vessels and eating utensils. T. pallidum is passed on mostly between children
living in poverty in very unsanitary environments and
with poor hygiene.
The skin, bones, and mucous membranes are
affected by bejel. Patches and ulcerated sores are common in the mouth, throat, and nasal passages.
Gummy lesions may form, even breaking through
the palate. Other findings may include a region of
swollen lymph nodes and deep bone pain in the legs.
Eventually, bones may become deformed.

Diagnosis
T. pallidum can be detected by microscopic study
of samples taken from the sores or lymph fluid.
However, since antibody tests don’t distinguish
between the types of syphilis, specific diagnosis of the
type of syphilis depends on the patient’s history, symptoms, and environment.

Treatment
Large doses of benzathine penicillin G given by
injection into the muscle can cure this disease in any
stage, although it may take longer and require
additional doses in later stages. If penicillin cannot
be given, the alternative is tetracycline. Since tetracycline can permanently discolor new teeth still forming,
it is usually not prescribed for children unless no viable
alternative is available.

Definition
Bejel, also known as endemic syphilis, is a
chronic but curable disease, seen mostly in children
in arid regions. Unlike the better-known venereal
510

Prognosis
Bejel is completely curable with antibiotic
treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Endemic disease—An infectious disease that
occurs frequently in a specific geographical locale.
The disease often occurs in cycles. Influenza is an
example of an endemic disease.
Lymph—This is a clear, colorless fluid found in
lymph vessels and nodes. The lymph nodes contain
organisms that destroy bacteria and other disease
causing organisms (also called pathogens).
Syphilis—This disease occurs in two forms. One is
a sexually transmitted disease caused by a bacteria.
The second form is not sexually transmitted, but
passed on by direct contact with the patient or
through use of shared food dishes and utensils.

Prevention
The World Health Organization (WHO) has
worked with many countries to prevent this and
other diseases, and the number of cases has been
reduced somewhat. Widespread use of penicillin has
been responsible for reducing the number of existing
cases, but the only way to eliminate bejel is by improving living and sanitation conditions.
Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

Jill S. Lasker

Benazepril see Angiotensin-converting
enzyme inhibitors

I Bence Jones protein test
Definition
Bence Jones proteins are small proteins (light
chains of immunoblobulin) found in the urine.
Testing for these proteins is done to diagnose and
monitor multiple myeloma and other similar diseases.

Purpose
Bence Jones proteins are considered the first
tumor marker. A tumor marker is a substance, made
GALE ENCYCLOPEDIA OF MEDICINE

by the body, that is linked to a certain cancer, or
malignancy. Bence Jones proteins are made by plasma
cells, a type of white blood cell. The presence of these
proteins in a person’s urine is associated with a malignancy of plasma cells.
Multiple myeloma, a tumor of plasma cells, is the
disease most often linked with Bence Jones proteins.
The amount of Bence Jones proteins in the urine indicates how much tumor is present. Physicians use Bence
Jones proteins testing to diagnose the disease as well as
to check how well the disease is responding to
treatment.
Other diseases involving cancerous or excessive
growth of plasma cells or cells similar to plasma cells
can cause Bence Jones proteins in the urine. These
diseases include: Waldenström’s macroglobulinemia,
some lymphomas and leukemias, osteogenic sarcoma,
cryoglobulinemia, malignant B-cell disease, amyloidosis,
light chain disease, and cancer that has spread to bone.

Description
Urine is the best specimen in which to look for
Bence Jones proteins. Proteins are usually too large to
move through a healthy kidney, from the blood into
the urine. Bence Jones proteins are an exception. They
are small enough to move quickly and easily through
the kidney into the urine.
A routine urinalysis will not detect Bence Jones
proteins. There are several methods used by laboratories to detect and measure these proteins. The classic
Bence Jones reaction involves heating urine to 140 8F
(608C). At this temperature, the Bence Jones proteins
will clump. The clumping disappears if the urine is
further heated to boiling and reappears when the
urine is cooled. Other clumping procedures using
salts, acids, and other chemicals are also used to detect
these proteins. These types of test will reveal whether
or not Bence Jones proteins are present, but not how
much is present.
A more complex procedure is done to measure the
exact amount of Bence Jones proteins. This procedure–immunoelectrophoresis–is usually done on
urine that has been collected for 24-hours.
The test is covered by insurance when medically
necessary. Results are usually available within several
days.

Preparation
Urine is usually collected throughout a 24-hour
time period. A person is given a large container in
511

Bence Jones protein test

KEY TERMS

Bender-Gestalt test

Purpose

KEY TERMS
Bence Jones protein—Small protein, composed of
a light chain of immunoglobulin, made by plasma
cells.
Multiple myeloma—A tumor of the plasma cells.
Plasma cells—A type of white blood cell.

which to collect the urine. The urine should be refrigerated until it is brought to the laboratory or physician’s office.

Normal results
Bence Jones proteins normally are not present in
the urine.

Abnormal results
Bence Jones proteins are present in 50–80% of
people with multiple myeloma. People with other
malignancies also can have a positive Bence Jones
proteins test, but less frequently.
Certain nonmalignant diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and
chronic renal insufficiency, can have Bence Jones proteins in the urine. High doses of penicillin or aspirin
before collecting the urine can give a false positive
result.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Nancy J. Nordenson

I Bender-Gestalt test
Definition
The Bender Visual Motor Gestalt test (or BenderGestalt test) is a psychological assessment used to
evaluate visual-motor functioning, visual-perceptual
skills, neurological impairment, and emotional disturbances in children and adults ages three and older.
512

The Bender-Gestalt is used to evaluate visualmotor maturity and to screen children for developmental delays. The test is also used to assess brain
damage and neurological deficits. Individuals who
have suffered a traumatic brain injury may be given
the Bender-Gestalt as part of a battery of neuropsychological measures, or tests.
The Bender-Gestalt is sometimes used in conjunction with other personality tests to determine the presence of emotional and psychiatric disturbances such
as schizophrenia.

Precautions
Psychometric testing requires a clinically trained
examiner. The Bender Visual Motor Gestalt Test
should be administered and interpreted by a trained
psychologist or psychiatrist. The Bender-Gestalt should
always be employed as only one element of a complete
battery of psychological or developmental tests, and
should never be used alone as the sole basis for a
diagnosis.

Description
The original Bender Visual Motor Gestalt test was
developed in 1938 by psychiatrist Lauretta Bender.
There are several different versions of the BenderGestalt available today (i.e., the Bender-Gestalt test;
Modified Version of the Bender-Gestalt test for
Preschool and Primary School Children; the Hutt
Adaptation of the Bender-Gestalt test; the Bender
Visual Motor Gestalt test for Children; the BenderGestalt test for Young Children; the Watkins BenderGestalt Scoring System; the Canter Background
Interference Procedure for the Bender-Gestalt test).
All use the same basic test materials, but vary in their
scoring and interpretation methods.
The standard Bender Visual Motor Gestalt test
consists of nine figures, each on its own 3 x 5 card. An
examiner presents each figure to the test subject one at
a time and asks the subject to copy it onto a single
piece of blank paper. The only instruction given to the
subject is that he or she should make the best reproduction of the figure possible. The test is not timed,
although standard administration time is typically
10-20 minutes. After testing is complete, the results
are scored based on accuracy and organization.
Interpretation depends on the form of the test in use.
Common features considered in evaluating the drawings are rotation, distortion, symmetry, and perseveration. As an example, a patient with frontal lobe injury
GALE ENCYCLOPEDIA OF MEDICINE

Neuropsychological test—A test or assessment
given to diagnose a brain disorder or disease.
Perserveration—The persistence of a repetitive
response after the cause of the response has been
removed, or the response continues to different
stimuli.
Visual-motor skills—Hand-eye coordination; in
the Bender-Gestalt test, visual-motor skills are measured by the subject’s ability to accurately perceive
and then reproduce figures.
Visual-perceptual skills—The capacity of the mind
and the eye to ‘‘see’’ something as it objectively
exists.

Benign prostatic hyperplasia see Enlarged
prostate
Benign prostatic hypertrophy see Enlarged
prostate
Benzocaine see Antiseptics

I Benzodiazepines
Definition
Benzodiazepines are medicines that help relieve
nervousness, tension, and other symptoms by slowing
the central nervous system.

Purpose
may reproduce the same pattern over and over
(perserveration).
The Bender-Gestalt can also be administered in a
group setting. In group testing, the figures are shown
to test subjects with a slide projector, in a test booklet,
or on larger versions of the individual test cards. Both
the individual and group- administered BenderGestalt evaluation may take place in either an outpatient or hospital setting. Patients should check
with their insurance plans to determine if these or
other mental health services are covered.

Normal results
Children normally improve in this test as they age,
but, because of the complexity of the scoring process,
results for the Bender-Gestalt should only be interpreted by a clinically trained psychologist or
psychiatrist.
Resources
ORGANIZATIONS

American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<http://www.apa.org>.
ERIC Clearinghouse on Assessment and Evaluation. 1131
Shriver Laboratory (Bldg 075).

Paula Anne Ford-Martin

Bends see Decompression sickness
Benign see Uterine fibroids
GALE ENCYCLOPEDIA OF MEDICINE

Benzodiazepines are a type of antianxiety drugs.
While anxiety is a normal response to stressful situations, some people have unusually high levels of anxiety that can interfere with everyday life. For these
people, benzodiazepines can help bring their feelings
under control. The medicine can also relieve troubling
symptoms of anxiety, such as pounding heartbeat,
breathing problems, irritability, nausea, and faintness.
Physicians may sometimes prescribe these drugs for
other conditions, such as muscle spasms, epilepsy and
other seizure disorders, phobias, panic disorder, withdrawal from alcohol, and sleeping problems. However,
this medicine should not be used every day for sleep
problems that last more than a few days. If used this
way, the drug loses its effectiveness within a few weeks.

Description
The family of antianxiety drugs known as benzodiazepines includes alprazolam (Xanax), chlordiazepoxide (Librium), diazepam (Valium), and lorazepam
(Ativan). These medicines take effect fairly quickly,
starting to work within an hour after they are taken.
Benzodiazepines are available only with a physician’s
prescription and are available in tablet, capsule,
liquid, or injectable forms.

Recommended dosage
The recommended dosage depends on the type of
benzodiazepine, its strength, and the condition for
which it is being taken. Doses may be different for
different people. Check with the physician who prescribed the drug or the pharmacist who filled the prescription for the correct dosage.
513

Benzodiazepines

KEY TERMS

Benzodiazepines

KEY TERMS
Anxiety—Worry or tension in response to real or
imagined stress, danger, or dreaded situations.
Physical reactions, such as fast pulse, sweating, trembling, fatigue, and weakness may accompany anxiety.
Asthma—A disease in which the air passages of the
lungs become inflamed and narrowed.
Bronchitis—Inflammation of the air passages of the
lungs.
Central nervous system—The brain and spinal
cord.
Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Emphysema—An irreversible lung disease in which
breathing becomes increasingly difficult.
Epilepsy—A brain disorder with symptoms that
include seizures.
Glaucoma—A condition in which pressure in the
eye is abnormally high. If not treated, glaucoma
may lead to blindness.
Myasthenia gravis—A chronic disease with symptoms that include muscle weakness and sometimes
paralysis.
Panic disorder—A disorder in which people have
sudden and intense attacks of anxiety in certain
situations. Symptoms such as shortness of breath,
sweating, dizziness, chest pain, and extreme fear
often accompany the attacks.
Phobia—An intense, abnormal, or illogical fear of
something specific, such as heights or open spaces.
Porphyria—A disorder in which porphyrins build
up in the blood and urine.
Porphyrin—A type of pigment found in living
things.
Seizure—A sudden attack, spasm, or convulsion.
Sleep apnea—A condition in which a person temporarily stops breathing during sleep.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug to which he or she has
become dependent.

Always take benzodiazepines exactly as directed.
Never take larger or more frequent doses, and do not
take the drug for longer than directed. If the medicine
does not seem to be working, check with the physician
514

who prescribed it. Do not increase the dose or stop
taking the medicine unless the physician says to do so.
Stopping the drug suddenly may cause withdrawal
symptoms, especially if it has been taken in large
doses or over a long period. People who are taking
the medicine for seizure disorders may have seizures
if they stop taking it suddenly. If it is necessary to stop
taking the medicine, check with a physician for directions on how to stop. The physician may recommend
tapering down gradually to reduce the chance of withdrawal symptoms or other problems.

Precautions
Seeing a physician regularly while taking benzodiazepines is important, especially during the first few
months of treatment. The physician will check to make
sure the medicine is working as it should and will note
unwanted side effects.
People who take benzodiazepines to relieve nervousness, tension, or symptoms of panic disorder
should check with their physicians every two to three
months to make sure they still need to keep taking the
medicine.
Patients who are taking benzodiazepines for sleep
problems should check with their physicians if they are
not sleeping better within 7-10 days. Sleep problems
that last longer than this may be a sign of another
medical problem.
People who take this medicine to help them sleep
may have trouble sleeping when they stop taking the
medicine. This effect should last only a few nights.
Some people, especially older people, feel
drowsy, dizzy, lightheaded, or less alert when using
benzodiazepines. The drugs may also cause clumsiness or unsteadiness. When the medicine is taken at
bedtime, these effects may even occur the next morning. Anyone who takes these drugs should not drive,
use machines or do anything else that might be
dangerous until they have found out how the drugs
affect them.
Benzodiazepines may also cause behavior changes
in some people, similar to those seen in people who act
differently when they drink alcohol. More extreme
changes, such as confusion, agitation, and hallucinations, also are possible. Anyone who starts having
strange or unusual thoughts or behavior while taking
this medicine should get in touch with his or her
physician.
Because benzodiazepines work on the central nervous system, they may add to the effects of alcohol and
other drugs that slow down the central nervous
GALE ENCYCLOPEDIA OF MEDICINE

Some benzodiazepines may change the results of
certain medical tests. Before having medical tests, anyone taking this medicine should alert the health care
professional in charge.
Children are generally more sensitive than adults
to the effects of benzodiazepines. This sensitivity may
increase the chance of side effects.
Older people are more sensitive than younger
adults to the effects of this medicine and may be at
greater risk for side effects. Older people who take
these drugs to help them sleep may be drowsy during
the day. Older people also increase their risk of falling
and injuring themselves when they take these drugs.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take benzodiazepines. Before taking these drugs,
be sure to let the physician know about any of these
conditions:
ALLERGIES. Anyone who has had unusual reac-

tions to benzodiazepines or other mood-altering
drugs in the past should let his or her physician know
before taking the drugs again. The physician should
also be told about any allergies to foods, dyes, preservatives, or other substances.
PREGNANCY. Some benzodiazepines increase the

likelihood of birth defects. Using these medicines during pregnancy may also cause the baby to become
dependent on them and to have withdrawal symptoms
after birth. When taken late in pregnancy or around
the time of labor and delivery, these drugs can cause
other problems in the newborn baby, such as
GALE ENCYCLOPEDIA OF MEDICINE

weakness, breathing problems, slow heartbeat, and
body temperature problems.
BREASTFEEDING. Benzodiazepines may pass into
breast milk and cause problems in babies whose
mothers taken the medicine. These problems include
drowsiness, breathing problems, and slow heartbeat.
Women who are breastfeeding their babies should not
use this medicine without checking with their
physicians.
OTHER MEDICAL CONDITIONS. Before using benzodiazepines, people with any of these medical problems should make sure their physicians are aware of
their conditions:


current or past drug or alcohol abuse



depression



severe mental illness



epilepsy or other seizure disorders



swallowing problems



chronic lung disease such as emphysema, asthma, or
chronic bronchitis



kidney disease



liver disease



brain disease



glaucoma



hyperactivity



myasthenia gravis



porphyria



sleep apnea

USE OF CERTAIN MEDICINES. Taking benzodiazepines with certain other drugs may affect the way the
drugs work or may increase the chance of side effects.

Side effects
The most common side effects are dizziness, lightheadedness, drowsiness, clumsiness, unsteadiness, and
slurred speech. These problems usually go away as the
body adjusts to the drug and do not require medical
treatment unless they persist or they interfere with
normal activities.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with the physician who prescribed the medicine
as soon as possible:


behavior changes



memory problems



difficulty concentrating
515

Benzodiazepines

system, such as antihistamines, cold medicine, allergy
medicine, sleep aids, medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants. They
may also add to the effects of anesthetics, including
those used for dental procedures. These effects may
last several days after treatment with benzodiazepines
ends. The combined effects of benzodiazepines and
alcohol or other CNS depressants (drugs that slow the
central nervous system) can be very dangerous, leading
to unconsciousness or, rarely, even death. Anyone taking benzodiazepines should not drink alcohol and
should check with his or her physician before using
any CNS depressants. Taking an overdose of benzodiazepines can also cause unconsciousness and possibly
death. Anyone who shows signs of an overdose or of the
effects of combining benzodiazepines with alcohol or
other drugs should get immediate emergency help.
Warning signs include slurred speech or confusion,
severe drowsiness, staggering, and profound weakness.

Bereavement



confusion

Resources



depression

OTHER



seizures (convulsions)

‘‘Medications.’’ National Institute of Mental Health Page.
1995. <http://www.nimh.nih.gov>.



hallucinations



sleep problems



increased nervousness, excitability, or irritability



involuntary movements of the body, including
the eyes



low blood pressure



unusual weakness or tiredness



skin rash or itching



unusual bleeding or bruising

I Bereavement



yellow skin or eyes

Definition



sore throat



sores in the mouth or throat



fever and chills

Patients who take benzodiazepines for a long time
or at high doses may notice side effects for several
weeks after they stop taking the drug. They should
check with their physicians if these or other troublesome symptoms occur:


irritability



nervousness



sleep problems

Other rare side effects may occur. Anyone who has
unusual symptoms during or after treatment with benzodiazepines should get in touch with his or her physician.

Interactions
Benzodiazepines may interact with a variety of
other medicines. When this happens, the effects of
one or both of the drugs may change or the risk
of side effects may be greater. Anyone who takes
benzodiazepines should let the physician know all
other medicines he or she is taking. Among the drugs
that may interact with benzodiazepines are:


Central nervous system (CNS) depressants such as
medicine for allergies, colds, hay fever, and asthma;
sedatives; tranquilizers; prescription pain medicine;
muscle relaxants; medicine for seizures; sleep aids;
barbiturates; and anesthetics.

Medicines other than those listed above may
interact with benzodiazepines. Be sure to check with
a physician or pharmacist before combining benzodiazepines with any other prescription or nonprescription
(over-the-counter) medicine.
516

Nancy Ross-Flanigan

Benzoyl peroxide see Antiacne drugs
Benztropine see Antiparkinson drugs

Bereavement refers to the period of mourning and
grief following the death of a beloved person or animal. The English word bereavement comes from an
ancient Germanic root word meaning ‘‘to rob’’ or ‘‘to
seize by violence.’’ Mourning is the word that is used to
describe the public rituals or symbols of bereavement,
such as holding funeral services, wearing black clothing, closing a place of business temporarily, or lowering a flag to half mast. Grief refers to one’s personal
experience of loss; it includes physical symptoms as
well as emotional and spiritual reactions to the loss.
While public expressions of mourning are usually
time-limited, grief is a process that takes most people
several months or years to work through.

Description
Bereavement is a highly individual as well as a
complex experience. It is increasingly recognized that
no two people respond the same way to the losses
associated with the death of a loved one. People’s
reactions to a death are influenced by such factors
as ethnic or religious traditions; personal beliefs
about life after death; the type of relationship ended
by death (relative, friend, colleague, etc.); the cause of
death; the person’s age at death; whether the death
was sudden or expected; and many others. In addition, the death of a loved one inevitably confronts
adults (and older adolescents) with the fact that they
too will die. As a result of this variety and emotional
complexity, most doctors and other counselors advise
people to trust their own feelings about bereavement,0 and grieve in the way that seems most helpful
to them.
It is also increasingly understood in the early
2000s that people can experience bereavement with
regard to other losses. Some examples of these
GALE ENCYCLOPEDIA OF MEDICINE

Columbine High School students in Littleton, Colorado,
grieving for their slain classmates. (Photo by David
Zalubowski. AP/Wide World Photos. Reproduced by permission.)

so-called ‘‘silent losses’’ include miscarriages in early
pregnancy, the death of a child in the womb shortly
before birth, or the news that a loved one has
Alzheimer’s disease or another illness that slowly
destroys their personality. In addition, many counselors recognize that bereavement has two dimensions,
the actual loss and the symbolic losses. For example, a
person whose teenage son or daughter is killed in an
accident suffers a series of symbolic losses—knowing
that their child will never graduate from high school,
get married, or have children—as well as the actual
loss of the adolescent to death.

Causes and symptoms
Causes
The immediate cause of bereavement is usually
the death of a loved friend or relative. There are a
GALE ENCYCLOPEDIA OF MEDICINE



The relationship with the dead person was a source
of pain rather than love and support. Examples
would include an abusive parent or spouse.



The person died in military service or in a natural,
transportation, or workplace disaster. Bereavement in
these cases is often made more difficult by intrusive
news reporters as well as anxiety over the loved one’s
possible physical or mental suffering prior to death.



The person was murdered. Survivors of homicide
victims often find the criminal justice system as well
as the media frustrating and upsetting.



The person is missing and presumed dead but their
death has not been verified. As a result, friends and
relatives may alternate between grief and hope that
the person is still alive.



The person committed suicide. Survivors may feel
guilt over their inability to foresee or prevent the
suicide, shame that the death was self-inflicted, or
anger at the person who committed suicide.



The relationship with the dead person cannot be
openly acknowledged. This situation often leads to
what is called disenfranchised grief. The most common instances are homosexual or extramarital sexual
relationships that have been kept secret for the sake
of spouses or other family members.



The loved one was an animal rather than a human
being. Western societies are only beginning to accept
that adults as well as children can grieve for a dead
animal; many adults still feel that there is ‘‘something wrong’’ about grieving for their pet. The question of euthanasia may be an additional source of
sorrow; even when the pet is terminally ill, many
people are very uneasy about making the decision
to end its life.
Symptoms

Bereavement typically affects a person’s physical
well-being as well as emotions. Common symptoms of
grief include changes in appetite and weight, fatigue,
insomnia and other sleep disturbances, loss of interest
in sex, low energy levels, nausea and vomiting, chest or
throat pain, and headache. People who have lost a
loved one in traumatic circumstances may have such
symptoms of post-traumatic stress disorder as an exaggerated startle response, visual or auditory hallucinations, or high levels of muscular tension.
Doctors and other counselors have identified four
stages or phases in uncomplicated bereavement:
517

Bereavement

number of situations, however, which can affect or
prolong the grief process:

Bereavement

taking on the loved one’s roles and responsibilities
as well as redefining their own identities.

KEY TERMS
Bibliotherapy—The use of books (usually self-help
or problem-solving works) to improve one’s understanding of personal problems and/or to heal painful feelings.
Biofield healing—A general term for a group of
alternative therapies based on the belief that the
human body is surrounded by an energy field (or
aura) that reflects the condition of the person’s
body and spirit. Rebalancing or repairing the
energy field is thought to bring about healing in
mind and body. Reiki, therapeutic touch, polarity
balancing, Shen therapy, and certain forms of color
therapy are considered forms of biofield healing.
Complicated grief—An abnormal response to
bereavement that includes unrelieved yearning for
the dead person, the complete loss of previous
positive beliefs or worldviews, and a general inability to function.
Disenfranchised grief—Grief that cannot be
openly expressed because the death or other loss
cannot be publicly acknowledged.
Euthanasia—The act of putting a person or animal
to death painlessly or allowing them to die by withholding medical services, usually because of a
painful and incurable disease.
Mourning—The public expression of bereavement;
it may include funerals and other rituals, special
clothing, and symbolic gestures.
Regression—A return to earlier, particularly infantile, patterns of thought and behavior.
Thanatology—The medical, psychological, or
legal study of death and dying.
Traumatic grief—Grief resulting from the loss of a
loved one in a traumatic situation (natural or transportation disaster, act of terrorism or mass murder, etc.)



Shock, disbelief, feelings of numbness. This initial
phase lasts about two weeks, during which the
bereaved person finally accepts the reality of the
loved one’s death.



Suffering the pain of grief. This phase typically lasts
for several months. Some people undergo a mild
temporary depression about six months after the
loved one’s death.



Adjusting to life without the loved one. In this phase
of bereavement, survivors may find themselves

518



Moving forward with life, forming new relationships, and having positive expectations of the future.
Most people reach this stage within one to two years
after the loved one’s death.

BEREAVEMENT IN CHILDREN. Children do not
experience bereavement in the same way as adolescents
and adults. Preschool children usually do not understand death as final and irreversible, and may talk or act
as if the dead pet or family member will wake up or
come back. Children between the ages of five and nine
are better able to understand the finality of death, but
they tend to assume it will not affect them or their
family. They are likely to be shocked and severely
upset by a death in their immediate family. In addition
to the physical disturbances that bereaved adults often
experience, children sometimes begin to act like infants
again (wanting bottle feeding, using baby talk, etc.)
This pattern of returning to behaviors characteristic of
an earlier life stage is called regression.
TRAUMATIC AND COMPLICATED GRIEF. Since the
early 1990s, thanatologists (doctors and other counselors who specialize in issues related to death and
dying) have identified two types of grief that do not
resolve normally with the passage of time. Traumatic
grief is defined as grief resulting from a sudden traumatic event that involves violent suffering, mutilation,
and/or multiple deaths; appears to be random or preventable; and often involves the survivor’s own brush
with death. The symptoms of traumatic grief are similar to those of post-traumatic stress disorder (PTSD).
Such events as the terrorist attacks of September 11,
2001, the East Asian tsunami of December 2004, and
airplane crashes or other transportation disasters may
produce traumatic grief in survivors.

In contrast to traumatic grief, complicated grief
does not necessarily result from a specific type of event
but rather refers to an abnormally intense and prolonged response to bereavement. While most people
are able to move through a period of bereavement and
recover a sense of purpose and meaning in life, people
with complicated grief feel as if their entire worldview
has been shattered. They cannot stop thinking of the
dead person, long to be with him or her, and may feel
that part of them died along with the loved one. They
sometimes start acting like the deceased person,
mimicking the symptoms of his or her illness, behaving in reckless ways, talking about ‘‘joining’’ the loved
one, or refusing to accept the reality of the death.
In general they are unable to function normally.
Complicated grief should not be regarded as simply
GALE ENCYCLOPEDIA OF MEDICINE

may take three years or longer to resolve, even with
appropriate treatment.

Prevention
Diagnosis
Bereavement is considered a normal response to a
death or other loss. A doctor who suspects that a
patient is suffering from traumatic or complicated
grief, however, may use various psychological inventories or questionnaires to see whether the patient
meets the criteria for PTSD, major depression, or
acute stress disorder. In addition, there are several specific questionnaires to help diagnose complicated grief.

Treatment
Most people do not require formal treatment
for bereavement. In the early 2000s, however, many
people choose to participate in support groups for
recently bereaved people or hospice follow-up programs
for relatives of patients who died in that hospice.
Bereavement support groups are particularly helpful in
guiding members through such common but painful
problems as disposing of the dead person’s possessions,
celebrating holidays without the loved one, coping with
anniversaries, etc.
Traumatic grief is usually treated in the same way
as post-traumatic stress, with temporary use of medications to control sleep disturbances and anxiety
symptoms along with long-term psychotherapy.
Those suffering from traumatic grief may also be
referred to support groups of people dealing with the
same type of sudden and violent loss. Some of these
organizations are listed below. Complicated grief is
usually managed with a combination of group and
individual psychotherapy.

Alternative treatment
Alternative therapies that have been reported to
help with the sleep disturbances and other physical
symptoms of bereavement include prayer and meditation; such movement therapies as yoga and tai chi;
therapeutic touch, Reiki, and other forms of biofield
healing; bibliotherapy and journaling; music therapy,
art therapy, hydrotherapy, and massage therapy.

Prognosis
Most people move through the stages of the normal grief process within several months to two years,
depending on the length and closeness of the relationship. Traumatic grief and complicated grief, however,
GALE ENCYCLOPEDIA OF MEDICINE

Bereavement is considered a normal response to
death and loss, which are universal human experiences. It should ordinarily be allowed to run its course;
most counselors maintain that trying to stifle or cut
short the grief process is more likely to cause emotional problems later on than to prevent them.
Resources
BOOKS

American Psychiatric Association.Diagnostic and Statistical
Manual of Mental Disorders, 4th edition, text revision.
Washington, DC: American Psychiatric Association,
2000.
Dossey, Larry, MD. Healing Beyond the Body: Medicine and
the Infinite Reach of the Mind. Boston and London:
Shambhala, 2001. The chapters on ‘‘The Return of
Prayer’’ and ‘‘Immortality’’ are particularly relevant to
bereavement.
‘‘Mood Disorders.’’ Section 15, Chapter 189 in The Merck
Manual of Diagnosis and Therapy, edited by Mark H.
Beers, MD, and Robert Berkow, MD. Whitehouse
Station, NJ: Merck Research Laboratories, 2005.
PERIODICALS

Bowles, Stephen B., Larry C. James, Diane S. Solursh, et al.
‘‘Acute and Post-Traumatic Stress Disorder after
Spontaneous Abortion.’’ American Family Physician 61
(March 15, 2000): 1689–1696.
Kersting, Karen. ‘‘A New Approach to Complicated Grief.’’
Monitor on Psychology 35 (November 2004): 51.
Lubit, Roy, MD. ‘‘Acute Treatment of Disaster Survivors.’’
eMedicine, 17 June 2004. <http://www.emedicine.com/
med/topic3540.htm>.
Ogrodniczuk, John S., William E. Piper, Anthony S. Joyce,
et al. ‘‘Differentiating Symptoms of Complicated Grief
and Depression among Psychiatric Outpatients.’’
Canadian Journal of Psychiatry/Revue canadienne de
psychiatrie 48 (March 2003): 87–93.
ORGANIZATIONS

Alzheimer’s Association. 225 North Michigan Avenue, 17th
Floor, Chicago, IL 60601-7633. (312) 335-8700.
24-hour hotline: (800) 272-3900. <http://www.alz.org>.
This website is an excellent resource for anyone with a
loved one suffering from Alzheimer’s or another
dementing illness.
American Academy of Child and Adolescent Psychiatry.
3615 Wisconsin Avenue, NW, Washington, DC
20016-3007. (202) 966-7300. Fax: (202) 966-2891.
<http://www.aacap.org.>.
American Veterinary Medical Association (AVMA). 1931
North Meacham Road, Suite 100, Schaumburg, IL
519

Bereavement

a subtype of clinical depression; the two conditions
may coexist or overlap in some patients but are nonetheless distinct entities.

Beriberi

60173-4360. <http://www.avma.org>. The AVMA
website includes links to resources about pet loss.
Dougy Center for Grieving Children and Families. 3909 SE
52nd Avenue, Portland, OR 97206. (866) 775-5683 or
(503) 775-5683. Fax: (503) 777-3097. <http://
www.grievingchild.org>. Provides age-appropriate
support groups, information, and referral services for
bereaved children and adolescents.
National Air Disaster Alliance/Foundation (NADA). 2020
Pennsylvania Avenue #315, Washington, DC 200061846. (888) 444-NADA. Fax: (336) 643-1394. <http://
www.planesafe.org>. NADA was founded in 1995
following the loss of USAir Flight 427 to meet the needs
of people who have lost loved ones in air disasters as
well as work for better transportation safety standards.
National Hospice and Palliative Care Organization
(NHPCO). 1700 Diagonal Road, Suite 625, Alexandria,
VA 22314. (703) 837-1500. Fax: (703) 837-1233.
<http://www.nho.org>. This website is a good source
of information about hospice-based bereavement services and support groups.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513 or (886) 615NIMH. <www.nimh.nih.gov.>
Tragedy Assistance Program for Survivors, Inc. (TAPS).
National Headquarters, 1621 Connecticut Avenue NW,
Suite 300, Washington, DC 20009. (202) 588-TAPS.
Hotline: (800) 959-TAPS. <http://www.taps.org>.
TAPS provides grief support for those who have lost a
loved one serving in the Armed Forces.
OTHER

Alzheimer’s Association. Fact Sheet: About Grief, Mourning
and Guilt. Chicago, IL: Alzheimer’s Association, 2004.
American Academy of Child and Adolescent Psychiatry
(AACAP). Children and Grief. AACAP Facts for
Families #8. Washington, DC: AACAP, 2004.
American Academy of Child and Adolescent Psychiatry
(AACAP). When a Pet Dies. AACAP Facts for
Families #78. Washington, DC: AACAP, 2000.
Harper, Linda R., PhD. Healing after the Loss of Your Pet.
<http://www.bestfriends.org/theanimals/pdfs/allpets/
PetLossHarper.pdf>.
National Institute of Mental Health (NIMH). Mental Health
and Mass Violence: Evidence-Based Early Psychological
Interventions for Victims/Survivors of Mass Violence.
NIH Publication No. 02-5138. Washington, DC: U. S.
Government Printing Office, 2002.
National Organization of Parents of Murdered Children
(POMC). Information Bulletin: Survivors of Homicide
Victims. <http://www.pomc.com/survivor.cfm>.

Rebecca Frey, PhD

Berger’s disease see Idiopathic primary renal
hematuric/proteinuric syndrome
520

I Beriberi
Definition
Beriberi is a disease caused by a deficiency of
thiamine (vitamin B1) that affects many systems of
the body, including the muscles, heart, nerves, and
digestive system. Beriberi literally means ‘‘I can’t, I
can’t’’ in Singhalese, which reflects the crippling effect
it has on its victims. It is common in parts of southeast
Asia, where white rice is the main food. In the United
States, beriberi is primarily seen in people with chronic
alcoholism.

Description
Beriberi puzzled medical experts for years as it
ravaged people of all ages in Asia. Doctors thought it
was caused by something in food. Not until the early
1900s did scientists discover that rice bran, the outer
covering that was removed to create the polished white
rice preferred by Asians, actually contained something
that prevented the disease. Thiamine was the first
vitamin identified. In the 1920s, extracts of rice polishings were used to treat the disease.
In adults, there are different forms of beriberi,
classified according to the body systems most affected.
Dry beriberi involves the nervous system; wet beriberi
affects the heart and circulation. Both types usually
occur in the same patient, with one set of symptoms
predominating.
A less common form of cardiovascular, or wet
beriberi, is known as ‘‘shoshin.’’ This condition
involves a rapid appearance of symptoms and acute
heart failure. It is highly fatal and is known to cause
sudden death in young migrant laborers in Asia whose
diet consists of white rice.
Cerebral beriberi, also known as WernickeKorsakoff syndrome, usually occurs in chronic alcoholics and affects the central nervous system (brain
and spinal cord). It can be caused by a situation that
aggravates a chronic thiamine deficiency, like an alcoholic binge or severe vomiting.
Infantile beriberi is seen in breastfed infants of
thiamine-deficient mothers, who live in developing
nations.
Although severe beriberi is uncommon in the
United States, less severe thiamine deficiencies do
occur. About 25% of all alcoholics admitted to a
hospital in the United States show some evidence of
thiamine deficiency.
GALE ENCYCLOPEDIA OF MEDICINE

B vitamins—This family of vitamins consists of
thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin, folic acid (B9),
and cobalamin (B12). They are interdependent and
involved in converting glucose to energy.
Coenzyme—A substance needed by enzymes to
produce many of the reactions in energy and protein metabolism in the body.
Edema—An excess accumulation of fluid in the
cells and tissues.

The following systems are most affected by
beriberi:


Gastrointestinal system. When the cells of the
smooth muscles in the digestive system and glands
do not get enough energy from glucose, they are
unable to produce more glucose from the normal
digestion of food. There is a loss of appetite, indigestion, severe constipation, and a lack of hydrochloric
acid in the stomach.



Nervous System. Glucose is essential for the central
nervous system to function normally. Early deficiency symptoms are fatigue, irritability, and poor
memory. If the deficiency continues, there is damage
to the peripheral nerves that causes loss of sensation
and muscle weakness, which is called peripheral neuropathy. The legs are most affected. The toes feel
numb and the feet have a burning sensation; the leg
muscles become sore and the calf muscles cramp. The
individual walks unsteadily and has difficulty getting
up from a squatting position. Eventually, the muscles
shrink (atrophy) and there is a loss of reflexes in the
knees and feet; the feet may hang limp (footdrop).



Cardiovascular system. There is a rapid heartbeat
and sweating. Eventually the heart muscle weakens.
Because the smooth muscle in the blood vessels is
affected, the arteries and veins relax, causing swelling, known as edema, in the legs.



Musculoskeletal system. There is widespread muscle pain caused by the lack of TPP in the muscle
tissue.

Enzyme—A protein that acts as a catalyst to produce chemical changes in other substances without
being changed themselves.
Metabolism—All the physical and chemical
changes that take place within an organism.
Peripheral neuropathy—A disease affecting the
portion of the nervous system outside the brain
and spinal chord. One or more nerves can be
involved, causing sensory loss, muscle weakness
and shrinkage, and decreased reflexes.
Thiamine pyrophosphate (TPP)—The coenzyme
containing thiamine that is essential in converting
glucose to energy.

Causes and symptoms
Thiamine is one of the B vitamins and plays an
important role in energy metabolism and tissue building. It combines with phosphate to form the coenzyme
thiamine pyrophosphate (TPP), which is essential in
reactions that produce energy from glucose or that
convert glucose to fat for storage in the tissues.
When there is not enough thiamine in the diet, these
basic energy functions are disturbed, leading to problems throughout the body.
Special situations, such as an over-active metabolism, prolonged fever, pregnancy, and breastfeeding, can increase the body’s thiamine requirements
and lead to symptoms of deficiency. Extended periods of diarrhea or chronic liver disease can result in
the body’s inability to maintain normal levels of
many nutrients, including thiamine. Other persons
at risk are patients with kidney failure on dialysis
and those with severe digestive problems who are
unable to absorb nutrients. Alcoholics are susceptible
because they may substitute alcohol for food and
their frequent intake of alcohol decreases the body’s
ability to absorb thiamine.
GALE ENCYCLOPEDIA OF MEDICINE

Infants who are breastfed by a thiaminedeficient mother usually develop symptoms of
deficiency between the second and fourth month of
life. They are pale, restless, unable to sleep, prone
to diarrhea, and have muscle wasting and edema in
their arms and legs. They have a characteristic,
sometimes silent, cry and develop heart failure and
nerve damage.

Diagnosis
A physical examination will reveal many of the
early symptoms of beriberi, such as fatigue, irritation, nausea, constipation, and poor memory, but
the deficiency may be difficult to identify.
Information about the individual’s diet and general
health is also needed.
There are many biochemical tests based on thiamine metabolism or the functions of TPP that can
detect a thiamine deficiency. Levels of thiamine can
be measured in the blood and urine and will be
reduced if there is a deficiency. The urine can be
521

Beriberi

KEY TERMS

Beriberi

collected for 24 hours to measure the level of thiamine excreted. Another reliable test measures the
effect of TPP on red blood cell activity since all
forms of beriberi affect the metabolism of red blood
cells.
An electroencephalogram (EEG), which measures
electrical activity in the brain, may be done to rule out
other causes of neurologic changes. Observing
improvements in the patient after giving thiamine
supplements will also confirm the diagnosis.

Treatment
Treatment with thiamine reverses the deficiency in
the body and relieves most of the symptoms. Severe
thiamine deficiency is treated with high doses of thiamine given by injection into a muscle (intramuscular)
or in a solution that goes into a vein (intravenously)
for several days. Then smaller doses can be given
either by injection or in pill form until the patient
recovers. Usually there are other deficiencies in the
B vitamins that will also need treatment.
The cardiovascular symptoms of wet beriberi can
respond to treatment within a few hours if they are
not too severe. Heart failure may require additional
treatment with diuretics that help eliminate excess
fluid and with heart-strengthening drugs like
digitalis.
Recovery from peripheral neuropathy and other
symptoms of dry beriberi may take longer and patients
frequently become discouraged. They should stay
active; physical therapy will also help in recovery.
Infantile beriberi is treated by giving thiamine to
both the infant and the breast feeding mother until
levels are normal.
In Wernicke-Korsakoff syndrome, thiamine should
be given intravenously or by injection at first because the
intestinal absorption of thiamine is probably impaired
and the patient is very ill. Most of the symptoms will be
relieved by treatment, though there may be residual
memory loss.
Excess thiamine is excreted by the body in the
urine, and negative reactions to too much thiamine
are rare. Thiamine is unstable in alkali solutions, so it
should not be taken with antacids or barbiturates.

Alternative treatment
Alternative treatments for beriberi deal first with
correcting the thiamine deficiency. As in conventional
treatments, alternative treatments for beriberi stress
a diet rich in foods that provide thiamine and other
522

B vitamins, such as brown rice, whole grains, raw
fruits and vegetables, legumes, seeds, nuts, and yogurt.
Drinking more than one glass of liquid with a meal
should be avoided, since this may wash out the vitamins before they can be absorbed by the body.
Thiamine should be taken daily, with the dose depending on the severity of the disease. Additional supplements of B vitamins, a multivitamin and mineral
complex, and Vitamin C are also recommended.
Other alternative therapies may help relieve the person’s symptoms after the thiamine deficiency is
corrected.

Prognosis
Beriberi is fatal if not treated and the longer the
deficiency exists, the sicker the person becomes. Most
of the symptoms can be reversed and full recovery is
possible when thiamine levels are returned to normal
and maintained with a balanced diet and vitamin supplements as needed.

Prevention
A balanced diet containing all essential nutrients
will prevent a thiamine deficiency and the development of beriberi. People who consume large quantities
of junk food like soda, pretzels, chips, candy, and high
carbohydrate foods made with unenriched flours may
be deficient in thiamine and other vital nutrients. They
may need to take vitamin supplements and should
improve their diets.
Dietary Requirements
The body’s requirements for thiamine are tied
to carbohydrate metabolism and expressed in terms
of total intake of calories. The current recommended dietary allowances (RDA) are 0.5 mg for
every 1000 calories, with a minimum daily intake
of 1 mg even for those who eat fewer than 2,000
calories in a day. The RDA for children and teenagers is the same as for adults: 1.4 mg daily for
males over age eleven, and 1.1 mg for females.
During pregnancy, an increase to 1.5 mg daily is
needed. Because of increased energy needs and the
secretion of thiamine in breast milk, breast feeding
mothers need 1.5 mg every day. In infants, 0.4 mg
is advised.
Food Sources
The best food sources of thiamine are lean
pork, beef, liver, brewer’s yeast, peas and beans,
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Beryllium—A steel-grey, metallic mineral used in
the aerospace and nuclear industries and in a variety of manufacturing processes.
Chelation therapy—A treatment using chelating
agents, compounds that surround and bind to target
substances allowing them to be excreted from the
body.
Corticosteroids—A group of anti-inflammatory
drugs.

During the milling process, rice is polished and all
the vitamins in the exterior coating of bran are lost.
Boiling the rice before husking preserves the vitamins
by distributing them throughout the kernel. Food
enrichment programs have eliminated beriberi in
Japan and the Phillipines.
Like all B vitamins, thiamine is water soluble,
which means it is easily dissolved in water. It will
leach out during cooking in water and is destroyed
by high heat and overcooking.
Resources
PERIODICALS

Ryan, Ruth, et al. ‘‘Beriberi Unexpected.’’ Psychosomatics
May-June 1997: 191-294.

Karen Ericson, RN

environment or process in which beryllium fumes or
particles become airborne. Working with pure beryllium, beryllium compounds (e.g. beryllium oxide), or
beryllium alloys causes occupational exposure. So do
jobs involving:


electronics



fiber optics



manufacturing ceramics, bicycle frames, golf clubs,
mirrors, and microwave ovens



mining



nuclear weapons and reactors



reclaiming scrap metal



space and atomic engineering



dental and laboratory technology

Berry aneurysm see Cerebral aneurysm

I Berylliosis
Definition
Berylliosis is lung inflammation caused by inhaling dust or fumes that contain the metallic element
beryllium. Found in rocks, coal, soil, and volcanic
dust, beryllium is used in the aerospace industry and
in many types of manufacturing. Berylliosis occurs in
both acute and chronic forms. In some cases, appearance of the disease may be delayed as much as 20 years
after exposure to beryllium.

Description
In the 1930s, scientists discovered that beryllium
could make fluorescent light bulbs last longer. During
the following decade, the hard, grayish metal was
identified as the cause of a potentially debilitating,
sometimes deadly disease characterized by shortness
of breath and inflammation, swelling, and scarring of
the lungs.
The manufacture of fluorescent light bulbs is no
longer a source of beryllium exposure, but serious
health hazards are associated with any work
GALE ENCYCLOPEDIA OF MEDICINE

Beryllium dust and fumes are classified as toxic air
pollutants by the Environmental Protection Agency
(EPA). It is estimated that 2–6% of workers exposed
to these contaminants eventually develop berylliosis.

Causes and symptoms
Coughing, shortness of breath, and weight loss
that begin abruptly can be a symptom of acute berylliosis. This condition is caused by beryllium air pollution that inflames the lungs making them rigid; it can
affect the eyes and skin as well. People who have acute
berylliosis are usually very ill. Most recover, but some
die of the disease.
Chronic berylliosis is an allergic reaction to longterm exposure to even low levels of beryllium dust or
fumes. A systemic disease that causes formation of
abnormal lung tissue and enlargement of the lymph
nodes, chronic berylliosis also may affect other parts
of the body. The symptoms of chronic berylliosis are
523

Berylliosis

whole or enriched grains, and breads. The more
refined the food, as in white rice, white breads,
and some cereals, the lower the thiamine. Many
food products are enriched with thiamine, along
with riboflavin, niacin, and iron, to prevent dietary
deficiency.

Beta blockers

largely the same as those seen in acute berylliosis, but
they develop more slowly.

Diagnosis
Berylliosis is initially suspected if a patient with
symptoms of the disease has a history of beryllium
exposure. A chest x ray shows characteristic changes
in the lungs. However, since these changes can resemble those caused by other lung diseases, further testing
may be necessary.
The beryllium lymphocyte proliferation test
(BeLPT), a blood test that can detect beryllium sensitivity (i.e. an allergic reaction to beryllium), is used to
screen individuals at risk of developing berylliosis.
When screening results reveal a high level of sensitivity, BeLPT is performed on cells washed from the
lungs. This test is now considered the most definitive
diagnostic test for berylliosis.

allergic reaction to these substances is an effective way
to control symptoms and prevent disease progression.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
Beryllium Support Group. P.O. Box 2021, Broomfield, CO
80038-2021. (303) 412-7065. <http://www.dimensional.com/~mhj>.
Environmental Health Center. 1025 Connecticut Ave., NW,
Washington, DC 20036. (202) 293-2270.

Maureen Haggerty

Beryllium pneumonosis see Berylliosis
Beryllium poisoning see Berylliosis
Beta-adrenergic blockers see beta blockers

Treatment
Individuals with beryllium sensitivity or earlystage berylliosis should be transferred from tasks
that involve beryllium exposure and regularly examined to determine whether the disease has progressed.
Acute berylliosis is a serious disease that occasionally may be fatal. Ventilators can help patients with
acute berylliosis breathe. Prompt corticosteroid therapy is required to lessen lung inflammation.
Chronic beryllium disease is incurable.
Corticosteroid therapy is often prescribed, but it is
not certain that steroids can alter the progression of
the disease, and they have no effect on scarring of lung
tissue. Cleansing the lungs of beryllium is a slow process, so long-term therapy may be required. Chelation
therapy is currently under investigation as a treatment
for the disease.

Prognosis
Most patients with acute berylliosis recover fully
7–10 days after treatment begins, and the disease
usually causes no after effects.
Patients whose lungs are severely damaged by
chronic berylliosis may experience fatal heart failure
because of the strain placed on the heart.

Prevention
Eliminating exposure to beryllium is the surest way
to prevent berylliosis. Screening workers who are
exposed to beryllium fumes or dust or who develop an
524

I Beta blockers
Definition
Beta blockers are medicines that affect the body’s
response to certain nerve impulses. This, in turn,
decreases the force and rate of the heart’s contractions, which lowers blood pressure and reduces the
heart’s demand for oxygen.

Purpose
The main use of beta blockers is to treat high
blood pressure. Some also are used to relieve the type
of chest pain called angina or to prevent heart attacks
in people who already have had one heart attack.
These drugs may also be prescribed for other conditions, such as migraine, tremors, and irregular heartbeat. In eye drop form, they are used to treat certain
kinds of glaucoma.

Description
Beta blockers, also known as beta-adrenergic
blockers, are available only with a physician’s
prescription. They come in capsule, tablet, liquid, and
injectable forms. Some common beta blockers are
atenolol (Tenormin), metoprolol (Lopressor), nadolol
(Corgard), propranolol (Inderal), and timolol
(Blocadren). Timolol and certain other beta blockers
are also sold in eye drop form for treating glaucoma.
GALE ENCYCLOPEDIA OF MEDICINE

Angina pectoris—A feeling of tightness, heaviness,
or pain in the chest, caused by a lack of oxygen in
the muscular wall of the heart.
Glaucoma—A condition in which pressure in the
eye is abnormally high. If not treated, glaucoma
may lead to blindness.
Migraine—A throbbing headache that usually
affects only one side of the head. Nausea, vomiting,
increased sensitivity to light, and other symptoms
often accompany migraine.

Blister packs of Tenormin LS (atenolol), a type of beta-receptor blocking drug or beta blocker. This type of drug is widely
used to treat angina, to lower blood pressure, or to correct
abnormal heart rhythms. (Photograph by Adam Hart-Davis,
Photo Researchers, Inc. Reproduced by permission.)

Eye drops that contain beta blockers include betaxolol
(Betoptic), cartelol (Ocupress), and timolol (Timoptic).

Recommended dosage
The recommended dosage depends on the type,
strength, and form of beta blocker and the condition
for which it is prescribed. The physician who prescribed the drug or the pharmacist who filled the prescription can recommend the correct dosage.
This medicine may take several weeks to noticeably lower blood pressure. Taking it exactly as directed is important.
This medicine should not be stopped without
checking with the physician who prescribed it. Some
conditions may get worse when patients stop taking
beta blockers abruptly. This may also increase the risk
of heart attack in some people. Because of these possible effects, it is important to keep enough medicine on
hand to get through weekends, holidays, and vacations.
Physicians may recommend that patients check
their pulse before and after taking this medicine. If the
pulse becomes too slow, circulation problems may result.

Precautions
Seeing a physician regularly while taking beta
blockers is important. The physician will check to
make sure the medicine is working as it should and
will watch for unwanted side effects. People who have
high blood pressure often feel perfectly fine. However,
GALE ENCYCLOPEDIA OF MEDICINE

they should continue to see their physicians even when
they feel well so that the physician can keep a close
watch on their condition. Patients also need to keep
taking their medicine even when they feel fine.
Beta blockers will not cure high blood pressure,
but will help control the condition. To avoid the serious health problems that high blood pressure can
cause, patients may have to take medicine for the rest
of their lives. Furthermore, medicine alone may not be
enough. Patients with high blood pressure may also
need to avoid certain foods and keep their weight
under control. The health care professional who is
treating the condition can offer advice on what measures may be necessary. Patients being treated for high
blood pressure should not change their diets without
consulting their physicians.
Anyone taking beta blockers for high blood pressure should not take any other prescription or over-thecounter medicine without first checking with his or her
physician. Some medicines may increase blood pressure.
Anyone who is taking beta blockers should be
sure to tell the health care professional in charge
before having any surgical or dental procedures or
receiving emergency treatment.
Some beta blockers may change the results of
certain medical tests. Before having medical tests, anyone taking this medicine should alert the health care
professional in charge.
Some people feel drowsy, dizzy, or lightheaded
when taking beta blockers. Anyone who takes these
drugs should not drive, use machines or do anything
else that might be dangerous until they have found out
how the drugs affect them.
Beta blockers may increase sensitivity to cold,
especially in older people or people who have poor
circulation. Anyone who takes this medicine should
525

Beta blockers

KEY TERMS

Beta blockers

dress warmly in cold weather and should be careful
not to be exposed to the cold for too long.

take beta blockers and who want to breastfeed their
babies should check with their physicians.

People who usually have chest pain when they
exercise or exert themselves may not have the pain
when they are taking beta blockers. This could lead
them to be more active than they should be. Anyone
taking this medicine should ask his or her physician
how much exercise and activity is safe.

OTHER MEDICAL CONDITIONS. Beta blockers may
increase breathing problems or make allergic reactions
more severe in people who have allergies, bronchitis, or
emphysema. However, while breathing diseases were
once thought to outrule use of beta blockers, new
research in 2004 shows that this may have been a
large misconception. A clinical trial showed that
more than 98% of patients with chronic obstructive
pulmonary disease safely used beta blockers. It is
advised for patients with emphysema and other serious pulmonary disease to check with a physician and
discuss the new findings.

Older people may be unusually sensitive to the
effects of beta blockers. This may increase the chance
of side effects.
Physicians may advise people taking beta blockers
to wear or carry medical identification indicating that
they are taking this medicine.
Special conditions
People who have certain medical conditions or
who are taking certain other medicines may have problems if they take beta blockers. Before taking these
drugs, the physician should know about any of these
conditions:
ALLERGIES. Anyone who has had unusual reac-

tions to beta blockers in the past should let his or her
physician know before taking the drugs again. The
physician should also be told about any allergies to
insect stings, medicines, foods, dyes, preservatives, or
other substances. In people with allergies to medicines,
foods, or insect stings, beta blockers may make the
allergic reactions more severe and harder to treat.
Anyone who has an allergic reaction while taking
beta blockers should get medical attention right
away and should make sure the physician in charge
knows that he or she is taking this medicine.
Beta blockers may also cause serious reactions in
people who take allergy shots. Anyone taking this
medicine should be sure to alert the physician before
having any allergy shots.
DIABETES. Beta blockers may make blood sugar
levels rise and may hide some symptoms of low
blood sugar. Diabetic patients should discuss these
possible problems with their physicians.
PREGNANCY. Some studies of beta blockers show
that these drugs cause problems in newborns whose
mothers use them during pregnancy. Other studies do
not show such effects. Women who are pregnant or
who may become pregnant should check with their
physicians about the use of beta blockers.
BREASTFEEDING. Some beta blockers pass into
breast milk and may cause breathing problems, slow
heartbeat, and low blood pressure in nursing babies
whose mothers take the drugs. Women who need to

526

In people with an overactive thyroid, stopping beta
blockers suddenly may cause an increase in symptoms.
Also, taking this medicine may hide a fast heartbeat,
which is one of the symptoms of overactive thyroid.
Effects of these drugs may be greater in people
with kidney or liver disease because the medicine is
cleared from the body more slowly.
Beta blockers may also make the following medical conditions worse:


Heart or blood vessel disease



Unusually slow heartbeat (bradycardia)



Myasthenia gravis (chronic disease causing muscle
weakness and possibly paralysis)



Psoriasis (itchy, scaly, red patches of skin)



Depression (now, or in the past).

Before using beta blockers, people with any of the
medical problems listed in this section should make
sure their physicians are aware of their conditions.
USE OF CERTAIN MEDICINES. Taking beta blockers
with certain other drugs may affect the way the drugs
work or may increase the chance of side effects.

Side effects
The most common side effects are dizziness, drowsiness, lightheadedness, sleep problems, unusual tiredness
or weakness, and decreased sexual ability. In men, this
can occur as impotence or delayed ejaculation. These
problems usually go away as the body adjusts to the
drug and do not require medical treatment unless they
persist or they interfere with normal activities. On the
positive side, research in 2004 showed that use of beta
blockers helps reduce risk for boen fractures.
More serious side effects are possible. If any of the
following side effects occur, the physician who prescribed
the medicine should be notified as soon as possible:
GALE ENCYCLOPEDIA OF MEDICINE

Breathing problems

Resources



Slow heartbeat

PERIODICALS



Cold hands and feet



Swollen ankles, feet, or lower legs



Mental depression.

‘‘Study Reveals Fears Over Beta Blockers in COPD
Unfounded.’’ Pulse September 13, 2004: 8.
‘‘Use of Beta Blockers Associated With Decreased Risk for
Fractures.’’ Life Science Weekly September 28, 2004:
944.

Other side effects may occur. Anyone who has
unusual symptoms after taking beta blockers should
get in touch with his or her physician.

Interactions
Beta blockers may interact with a number of other
medicines. When this happens, the effects of one or
both of the drugs may change or the risk of side effects
may be greater. Anyone who takes beta blockers
should let the physician know all other medicines he
or she is taking. Among the drugs that may interact
with beta blockers are:


Calcium channel blockers and other blood pressure
drugs. Using these drugs with beta blockers may
cause unwanted effects on the heart.



Insulin and diabetes medicines taken by mouth. Beta
blockers cause high blood sugar or hide the symptoms of low blood sugar.



Monoamine oxidase inhibitors (MAO) such as phenelzine (Nardil) or tranylcypromine (Parnate), used
to treat conditions including depression and
Parkinson’s disease. Taking beta blockers at the
same time or within two weeks of taking MAO inhibitors may cause severe high blood pressure.



Airway-opening drugs (bronchodilators) such as aminophylline (Somophyllin), dyphylline (Lufyllin)
oxtriphylline
(Choledyl),
or
theophylline
(Somophyllin-T). When combined with beta blockers, the effects of both the beta blockers and the
airway-opening drugs may be lessened.



Cocaine. High blood pressure, fast heartbeat, and
heart problems are possible when cocaine and beta
blockers are combined. Also, cocaine may interfere
with the effects of beta blockers.



Allergy shots or allergy skin tests. Beta blockers may
increase the chance of serious reactions to these
medicines.

The list above may not include every drug that
interacts with beta blockers. Checking with a physician or pharmacist before combining beta blockers
with any other prescription or nonprescription (overthe-counter) medicine is advised.
GALE ENCYCLOPEDIA OF MEDICINE

Nancy Ross-Flanigan
Teresa G. Odle

Beta-thalassemia see Thalassemia
Betamethasone see Corticosteroids

I Beta -microglobulin test
2

Definition
Beta2-microglobulin is a protein found on the surface of many cells. Testing is done primarily when
evaluating a person for certain kinds of cancer affecting white blood cells including chronic lymphocytic
leukemia, non-Hodgkin’s lymphoma, and multiple
myeloma or kidney disease.

Purpose
Beta2-microglobulin is plentiful on the surface of
white blood cells. Increased production or destruction
of these cells causes Beta2-microglobulin levels in the
blood to increase. This increase is seen in people with
cancers involving white blood cells, but it is particularly meaningful in people newly diagnosed with multiple myeloma. Multiple myeloma is a malignancy
(cancer) of a certain kind of white blood cell, called a
plasma cell. At the time of diagnosis, the Beta2-microglobulin levels reflect how advanced the disease is and
the likely prognosis for that person.
When kidney disease is suspected, comparing
blood and urine levels helps identify where the kidney
is damaged. Beta2-microglobulin normally is filtered
out of the blood by the kidney’s glomeruli (a round
mass of capillary loops leading to each kidney tubule),
only to be partially reabsorbed back into the blood
when it reaches the kidney’s tubules. In glomerular
kidney disease, the glomeruli can’t filter it out of the
blood, so levels increase in the blood and decrease in
the urine. In tubular kidney disease, the tubules can’t
reabsorb it back into the blood, so urine levels rise and
blood levels fall. After a kidney transplant, increased
blood levels may be an early sign of rejection.
527

Beta2-microglobulin test



Bile duct cancer

KEY TERMS
Beta2-microglobulin—A protein found on the surface of many cells, particularly white blood cells.
Chronic lymphocytic leukemia—A cancer of the
blood cells characterized by large numbers of cancerous, mature white blood cells and enlarged
lymph nodes.
Glomerular kidney disease—Disease of the kidney
that affects the glomeruli, the part of the kidney that
filters certain substances out of the blood.
Muliple myeloma—A malignancy (cancer) of a certain kind of white blood cell, called a plasma cell.
Non-Hodgkin’s lymphoma—Cancer that originates in the lymphatic system and typically spreads
throughout the body.
Tubular kidney disease—Disease of the kidney that
affect the tubules, the part of the kidney that allows
certain substances to be reabsorbed back into the
blood.

Increased urinary levels are found in people with
kidney damage caused by high exposure to the heavy
metals cadmium and mercury. Periodic testing of
workers exposed to these metals helps to detect beginning kidney damage.
Beta2-microglobulin levels also rise during infection with some viruses, including cytomegalovirus and
human immunodeficiency virus (HIV). Studies show
that as HIV disease advances, beta2-microglobulin
levels rise.

inserts a needle into that vein. Vacuum action draws
the blood through the needle into an attached tube.
Collection of the sample takes only a few minutes.
Urine may be a single collection or collected
throughout a 24-hour time period. The urine should
be refrigerated until it is brought to the laboratory and
must not become acidic.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to the
puncture site until the bleeding stops reduces bruising.
Warm packs on the puncture site relieve discomfort.

Normal results


Serum: less than or equ to 2.7 g/ml



Urine: less than 1 mg 24 hours 0–160 g/L

Abnormal results
The meaning of an abnormal result varies with the
clinical condition of the person tested. In a person with
multiple myeloma, a higher level means a poorer prognosis than a lower level. In a person with kidney disease, an increased blood level means the problem is
tubular, not glomerular. In a kidney transplant
patient, an increase may be a sign of rejection, toxic
amounts of antirejection medication, or a viral infection. An increased level in a worker exposed to cadmium or mercury may signal beginning kidney
damage and in a person with HIV, advancing disease.
Resources
BOOKS

Description
Testing methods vary, but most involve adding
the person’s serum–the yellow, liquid part of blood–
or urine to one or more substances that bind to beta2microglobulin in the serum or urine. The amount of
the substance(s) bound to beta2-microglobulin is measured and the original amount of beta2-microglobulin
is determined.
The test is covered by insurance when medically
necessary. Results are usually available the next day.

Preparation
The blood test requires 5 mL of blood. A healthcare worker ties a tourniquet on the person’s upper
arm, locates a vein in the inner elbow region, and
528

Lehmann, Craig A. Saunders Manual of Clinical Laboratory
Science. Philadelphia: W. B. Saunders Co., 1998.

Nancy J. Nordenson

Bile duct infection see Cholangitis

I Bile duct cancer
Definition
Bile duct cancer, or cholangiocarcinoma, is a
malignant tumor of the bile ducts within the liver
(intrahepatic), or leading from the liver to the small
GALE ENCYCLOPEDIA OF MEDICINE

Angiography—Radiographic examination of blood
vessels after injection with a special dye.
Cholangiography—Radiographic examination of
the bile ducts after injection with a special dye.
Computed tomography—Radiographic examination that obtains cross-sectional images of the
body.
Jaundice—Yellowish staining of the skin and eyes
due to excess bilirubin in the bloodstream.
Lymphatic—Pertaining to lymph, the clear fluid
that is collected from tissues, flows through special
vessels, and joins the venous circulation.

100,000 people per year, but it is more common in
Southeast Asia. It occurs in men only slightly more
often than in women and it is most commonly diagnosed in people in their 50s and 60s. In fact, about
65% of patients with bile duct cancer are over age 65.

Causes and symptoms
A number of risk factors are associated with the
development of bile duct cancer:


Primary sclerosing cholangitis. This disease is characterized by extensive scarring of the biliary tract,
sometimes associated with inflammatory bowel
disease.



Choledochal cysts. These are abnormal dilatations of
the biliary tract that usually form during fetal development. There is evidence that these cysts may rarely
arise during adulthood.



Hepatolithiasis. This is the condition of stone formation within the liver (not including gallbladder stones).



Liver flukes. Parasitic infection with certain worms is
thought to be at least partially responsible for the
higher prevalence of bile duct cancer in Southeast
Asia.



Thorotrast. This is a chemical that was previously
injected intravenously during certain types of x rays.
It is not in use anymore. Exposure to Thorotrast has
been implicated in the development of cancer of the
liver as well as the bile ducts.

Metastasis—The spread of cancerous tumor cells
from one part of the body to another.
Resection—To surgically remove a part of the body
Stent—Slender hollow catheter or rod placed
within a vessel or duct to provide support or maintain patency.
Ultrasound—Radiographic imaging technique utilizing high frequency sound waves.

intestine (extrahepatic). It is a rare tumor with poor
outcome for most patients.

Description
Bile is a substance manufactured by the liver that
aids in the digestion of food. Bile ducts are channels
that carry the bile from the liver to the small intestine.
Like the tributaries of a river, the small bile ducts in
the liver converge into two large bile ducts called the
left and right hepatic ducts. These exit the liver and
join to form the common hepatic duct. The gallbladder, which concentrates and stores the bile, empties
into the common hepatic duct to form the common
bile duct. Finally, this large duct connects to the small
intestine where the bile can help digest food.
Collectively, this network of bile ducts is called the
biliary tract.
Bile duct cancer originates from the cells that line
the inner surface of the bile ducts. A tumor may arise
anywhere along the biliary tract, either within or outside of the liver. Bile duct tumors are typically slowgrowing tumors that spread by local invasion of neighboring structures and by way of lymphatic channels.
Bile duct cancer is an uncommon malignancy. In
the United States, approximately one case arises per
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms
Jaundice is the first symptom in 90% of patients.
This occurs when the bile duct tumor causes an
obstruction in the normal flow of bile from the liver
to the small intestine. Bilirubin, a component of bile,
builds up within the liver and is absorbed into the
bloodstream in excess amounts. This can be detected
in a blood test, but it can also manifest as yellowish
discoloring of the skin and eyes. The bilirubin in the
bloodstream also makes the urine appear dark.
Additionally, the patient may experience generalized
itching due to the deposition of bile components in the
skin. Normally, a portion of the bile is excreted in
stool; bile actually gives stool its brown color. But
when the biliary tract is obstructed by tumor, the
stools may appear pale.
Abdominal pain, fatigue, weight loss, and poor
appetite are less common symptoms. Occasionally, if
obstruction of the biliary tract causes the gallbladder
to swell enormously yet without causing pain, the
physician may be able to feel the gallbladder during a
529

Bile duct cancer

KEY TERMS

Bile duct cancer

physical examination. Sometimes the biliary tract can
become infected, but this is normally a rare consequence of invasive tests. Infection causes fever, chills,
and pain in the right upper portion of the abdomen.

Diagnosis
Certain laboratory tests of the blood may aid in
the diagnosis. The most important one is the test for
elevated bilirubin levels in the bloodstream. Levels of
alkaline phosphatase and CA 19-9 may also be
elevated.
When symptoms, physical signs, and blood tests
point toward an abnormality of the biliary tract, the
next step involves radiographic exams. Ultrasound,
computed tomography (CT scan), and magnetic resonance imaging (MRI) are noninvasive and rapid. In
recent years, MRI has become the favored imaging
choice for initial diagnosis of cholangiocarcinoma
when the exam is available and affordable or covered
by insurance. These tests can often detect the actual
tumor as well as dilatation of the obstructed biliary
tract. If these tests indicate the presence of a tumor,
cholangiography is required. This procedure involves
injecting dye into the biliary tract to obtain anatomic
images of the bile ducts and the tumor. The specialist
that performs this test can also insert small tubes, or
stents, into a partially obstructed portion of the bile
duct to prevent further obstruction by growth of the
tumor. This is vitally important since it may be the
only intervention that is possible in certain patients.
Cholangiography is an invasive test that carries a
small risk of infection of the biliary tract. The objective
of these radiological tests is to determine the size and
location of the tumor, as well as the extent of spread to
nearby structures.
The treatment of bile duct tumors is usually not
affected by the specific type of cancer cells that comprise the tumor. For this reason, some physicians
forego biopsy of the tumor.

Treatment
The treatment is with surgical resection (removal)
of the tumor and all involved structures. Unfortunately,
sometimes the cancer has already spread too far when
the diagnosis is made. Thus, in the treatment of bile
duct cancer, the first question to answer is if the tumor
may be safely resected by surgery with reasonable
benefit to the patient. If the cancer involves
certain blood vessels or has spread widely throughout
the liver, resection may not be possible. Sometimes
further invasive testing is required.
530

Angiography can determine if the blood vessels are
involved. Laparoscopy is a surgical procedure that
allows the surgeon to directly assess the tumor and
nearby lymph nodes without making a large incision
in the abdomen. Only about 45% of bile duct cancers
are ultimately resectable.
If the tumor is resectable, and the patient is
healthy enough to tolerate the operation, the specific
type of surgery performed depends on the location of
the tumor. For tumors within the liver or high up in
the biliary tract, resection of part of the liver may be
required. Tumors in the middle portion of the biliary
tract can be removed alone. Tumors of the lower end
of the biliary tract may require extensive resection of
part of the pancreas, small intestine, and stomach to
ensure complete resection.
Unfortunately, sometimes the cancer appears
resectable by all the radiological and invasive tests,
but is found to be unresectable during surgery. In
this scenario, a bypass operation can relieve the biliary
tract obstruction, but does not remove the tumor
itself. This does not produce a cure but it can offer a
better quality of life for the patient.

Prognosis
Prognosis depends on the stage and resectability
of the tumor. If the patient cannot undergo surgical
resection, the survival rate is commonly less than one
year. If the tumor is resected, the survival rate
improves, with 20% of these patients surviving past
five years.
Clinical trials
Studies of new treatments in patients are known as
clinical trials. These trials seek to compare the standard method of care with a new method, or the trials
may be trying to establish whether one treatment is
more beneficial for certain patients than others.
Sometimes, a new treatment that is not being offered
on a wide scale may be available to patients participating in clinical trials, but participating in the trials may
involve some risk. To learn more about clinical trials,
patients can call the National Cancer Institute (NCI)
at 1-800-4-CANCER or visit the NCI web site for
patients at <http://www.cancertrials.nci.nih.gov>.

Prevention
Other than the avoidance of infections caused by
liver flukes, there are no known preventions for this
cancer.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Abeloff, Martin D., editor. ‘‘Cholangiocarcinoma.’’ In
Clinical Oncology. 2nd ed. New York: Churchill
Livingstone, 2000, pp.1722-1723.
Ahrendt, Steven A., and Henry A. Pitt. ‘‘Biliary Tract.’’ In
Sabiston Textbook of Surgery, edited by Courtney
Townsend Jr., 16th ed. Philadelphia: W.B. Saunders
Company, 2001, pp. 1076-1111.
PERIODICALS

‘‘COX–2 Promoter Enhances the Efficacy of
Cholangiosarcoma Gene Therapy.’’ Cancer Weekly
(May 20, 2003): 167.
Khan, S.A., et al. ‘‘Guidelines for the Diagnosis and
Treatment of Cholangiosarcoma: Consensus
Document.’’ Gut (November 2002): vi1–9.
ORGANIZATIONS

The American Cancer Society. 1-800-ACS 2345. <http://
www.cancer.org>.
American Liver Foundation.1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
National Cancer Institute (National Institutes of Health).
9000 Rockville Pike, Bethesda, MD 20892. (800) 4226237. <http://www.nci.nih.gov>.

Kevin O. Hwang M.D.
Teresa G. Odle

Bile duct atresia see Biliary atresia
Bile flow obstruction see Cholestasis
Bilharziasis see Schistosomiasis

I Biliary atresia
Definition
Biliary atresia is the failure of a fetus to develop an
adequate pathway for bile to drain from the liver to the
intestine.

rivers, until they all pour into a single duct that empties
into the duodenum (first part of the small intestine).
Between the liver and the duodenum this duct has a side
channel connected to the gall bladder. The gall bladder
stores bile and concentrates it, removing much of its
water content. Then, when a meal hits the stomach, the
gall bladder contracts and empties its contents.
Bile is a mixture of waste chemicals that the liver
removes from the circulation and excretes through the
biliary system into the intestine. On its way out, bile
assists in the digestion of certain nutrients. If bile
cannot get out because the channels are absent or
blocked, it backs up into the liver and eventually into
the rest of the body. The major pigment in bile is a
chemical called bilirubin, which is yellow. Bilirubin is a
breakdown product of hemoglobin (the red chemical
in blood that carries oxygen). If the body accumulates
an excess of bilirubin, it turns yellow (jaundiced). Bile
also turns the stool brown. Without it, stools are the
color of clay.

Causes and symptoms
It is possible that a viral infection is responsible
for this disease, but evidence is not yet convincing. The
cause remains unknown.
The affected infant will appear normal at birth
and during the newborn period. After two weeks the
normal jaundice of the newborn will not disappear,
and the stools will probably be clay-colored. At this
point, the condition will come to the attention of a
physician. If not, the child’s abdomen will begin to
swell, and the infant will get progressively more ill.
Nearly all untreated children will die of liver failure
within two years.

Diagnosis
The persistence of jaundice beyond the second
week in a newborn with clay-colored stools is a sure
sign of obstruction to the flow of bile. An immediate
evaluation that includes blood tests and imaging of the
biliary system will confirm the diagnosis.

Description
Biliary atresia is the most common lethal liver
disease in children, occurring once every 10,000–
15,000 live births. Half of all liver transplants are
done for this reason.
The normal anatomy of the bile system begins
within the liver, where thousands of tiny bile ducts
collect bile from liver cells. These ducts merge into
larger and larger channels, like streams flowing into
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Surgery is the only treatment. Somehow the surgeon must create an adequate pathway for bile to
escape the liver into the intestine. The altered anatomy
of the biliary system is different in every case, calling
upon the surgeon’s skill and experience to select and
execute the most effective among several options. If
the obstruction is only between the gall bladder and
531

Biliary atresia

Resources

Biliary atresia

Cystic duct

Liver

Gallbladder

Pyloric sphincter

Common bile duct

Duodenum

Pancreas

Biliary atresia is a congenital condition in which the pathway for bile to drain from the liver to the intestine is undeveloped. It is
the most common lethal liver disease in children. (Illustration by Electronic Illustrators Group).

KEY TERMS
Duodenum—The first part of the small intestine,
beginning at the outlet of the stomach.
Hemoglobin—The red, iron-containing chemical
in the blood that carries oxygen to the tissues.
Jaundice—The yellow color taken on by a patient
whose liver is unable to excrete bilirubin. A normal
condition in the first week of life due to the infant’s
delayed ability to process certain waste products.
Kernicterus—A potentially lethal disease of newborns caused by excessive accumulation of the bile
pigment bilirubin.

the intestine, it is possible to attach a piece of intestine
directly to the gall bladder. More likely, the upper
biliary system will also be inadequate, and the surgeon
will attach a piece of intestine directly to the liver–the
Kasai procedure. In its wisdom, the body will discover
that the tiny bile ducts in that part of the liver are
discharging their bile directly into the intestine. Bile
532

will begin to flow in that direction, and the channels
will gradually enlarge. Survival rates for the Kasai
procedure are commonly 50% at five years and 15%
at 10 years. Persistent disease in the liver gradually
destroys the organ.

Prognosis
Before liver transplants became available, even
prompt and effective surgery did not cure the whole
problem. Biliary drainage can usually be established,
but the patients still have a defective biliary system
that develops progressive disease and commonly leads
to an early death. Transplantation now achieves up to
90% one-year survival rates and promises to prevent
the chronic disease that used to accompany earlier
procedures.

Prevention
The specific cause of this birth defect is unknown,
so all that women can do is to practice the many
general preventive measures, even before they
conceive.
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Feldman, Mark, et al. ‘‘Diseases of the Bile Ducts.’’
Sleisenger & Fordtran’s Gastrointestinal and Liver
Disease. Philadelphia: W. B. Saunders Co., 1998.

J. Ricker Polsdorfer, MD

Biliary duct cancer see Gallbladder cancer
Biliary tract cancer see Bile duct cancer
Bilirubin test see Liver function tests

I Binge-eating disorder
Definition
Binge eating disorder (BED) is characterized by a
loss of control over eating behaviors. The binge eater
consumes unnaturally large amounts of food in a short
time period, but unlike a bulimic, does not regularly
engage in any inappropriate weight-reducing behaviors (for example, excessive exercise, vomiting, taking
laxatives) following the binge episodes.

Description
BED typically strikes individuals sometime between
adolescence and the early twenties. Because of the nature of the disorder, most BED patients are overweight
or obese. Studies of weight loss programs have shown
that an average of 30% of individuals enrolling in these
programs report binge eating behavior.

KEY TERMS
Bulimia—An eating disorder characterized by
binge eating and inappropriate compensatory
behavior, such as vomiting, misusing laxatives, or
excessive exercise.
Cognitive behavioral therapy—A therapy that pays
particular attention to a patient’s behavior and
thinking processes rather than underlying psychological causes of an activity.

importance of food, for example, as a source of comfort in times of emotional distress. As children, BED
patients may have been taught to clean their plate
regardless of their appetite, or that finishing a meal
made them a ‘‘good’’ girl or boy. Cultural attitudes
towards beauty and thinness may also be a factor in
the BED equation.
During binge episodes, BED patients experience a
definite sense of lost control over their eating. They eat
quickly and to the point of discomfort even if they
aren’t hungry. They typically binge alone two or more
times a week, and often feel depressed and guilty once
the episode has concluded.

Diagnosis
Binge eating disorder is usually diagnosed and
treated by a psychiatrist and/or a psychologist. In
addition to an interview with the patient, personality
and behavioral inventories, such as the Minnesota
Multiphasic Personality Inventory (MMPI), may be
administered as part of the assessment process. One
of several clinical inventories, or scales, may also be
used to assess depressive symptoms, including the
Hamilton Depression Scale (HAM-D) or Beck
Depression Inventory (BDI). These tests may be administered in an outpatient or hospital setting.

Causes and symptoms
Binge eating episodes may act as a psychological
release for excessive emotional stress. Other circumstances that may predispose an individual to BED
include heredity and affective disorders, such as
major depression. BED patients are also more likely
to have a comorbid, or co-existing, diagnosis of impulsive behaviors (for example, compulsive buying), posttraumatic stress disorder (PTSD), panic disorder, or
personality disorders.
Individuals who develop BED often come from
families who put an unnatural emphasis on the
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Many BED individuals binge after long intervals
of excessive dietary restraint; therapy helps normalize
this pattern. The initial goal of BED treatment is
to teach the patient to gain control over his eating
behavior by focusing on eating regular meals and
avoiding snacking. Cognitive-behavioral therapy,
group therapy, or interpersonal psychotherapy may
be employed to uncover the emotional motives, distorted thinking, and behavioral patterns behind the
binge eating.
533

Binge-eating disorder

Biliary atresia is a congenital condition in which
the pathway for bile to drain from the liver to the
intestine is undeveloped. It is the most common lethal
liver disease in children.

Biofeedback

Because the prevalence of depression in BED
patients is high, psychopharmacological treatment
with antidepressants may also be prescribed. Once
the binge eating behavior is curbed and depressive
symptoms are controlled, the physical symptoms
of BED can be addressed. The overweight BED
patient may be placed on a moderate exercise program and a nutritionist may be consulted to educate
the patient on healthy food choices and strategies for
weight loss.

Prognosis
The poor dietary habits and obesity that are symptomatic of BED can lead to serious health problems,
such as high blood pressure, heart attacks, and diabetes, if left unchecked. BED is a chronic condition
that requires ongoing medical and psychological management. To bring long-term relief to the BED patient,
it is critical to address the underlying psychological
causes behind binge eating behaviors. It appears that
up to 50% of BED patients will stop bingeing with
cognitive behavioral therapy (CBT).
Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<http://www.apa.org>.
Eating Disorders Awareness and Prevention. 603 Stewart
St., Suite 803, Seattle, WA 98101. (206) 382-3587.
National Eating Disorders Organization (NEDO). 6655
South Yale Ave., Tulsa, OK 74136. (918) 481-4044.
Overeaters Anonymous World Service Office. 6075 Zenith
Ct. NE, Rio Rancho, NM 87124. (505) 891-2664.
<http://www.overeatersanonymous.org>.

Paula Anne Ford-Martin

I Biofeedback
Definition
Biofeedback, or applied psychophysiological
feedback, is a patient-guided treatment that teaches
an individual to control muscle tension, pain, body
temperature, brain waves, and other bodily functions
and processes through relaxation, visualization, and
other cognitive control techniques. The name
534

A patient undergoing biofeedback therapy.
Researchers, Inc. Reproduced by permission.)

(Photo

biofeedback refers to the biological signals that are
fed back, or returned, to the patient in order for the
patient to develop techniques of manipulating them.

Purpose
Biofeedback has been used to successfully treat a
number of disorders and their symptoms, including
temporomandibular joint disorder (TMJ), chronic
pain, irritable bowel syndrome (IBS), Raynaud’s
syndrome, epilepsy, attention-deficit hyperactivity
disorder (ADHD), migraine headaches, anxiety,
depression, traumatic brain injury, and sleep disorders.
Illnesses that may be triggered at least in part by
stress are also targeted by biofeedback therapy. Certain
types of headaches, high blood pressure, bruxism (teeth
grinding), post-traumatic stress disorder, eating disorders, substance abuse, and some anxiety disorders may
be treated successfully by teaching patients the ability
to relax and release both muscle and mental tension.
Biofeedback is often just one part of a comprehensive
treatment program for some of these disorders.
NASA has used biofeedback techniques to treat
astronauts who suffer from severe space sickness, during which the autonomic nervous system is disrupted.
Scientists at the University of Tennessee have adapted
these techniques to treat individuals suffering from
severe nausea and vomiting that is also rooted in
autonomic nervous system dysfunction.
GALE ENCYCLOPEDIA OF MEDICINE

Autonomic nervous system—The part of the nervous system that controls so-called involuntary
functions, such as heart rate, salivary gland secretion, respiratory function, and pupil dilation.
Bruxism—Habitual, often unconscious, grinding of
the teeth.
Epilepsy—A neurological disorder characterized
by the sudden onset of seizures.
Placebo effect—Placebo effect occurs when a treatment or medication with no known therapeutic
value (a placebo) is administered to a patient, and
the patient’s symptoms improve. The patient
believes and expects that the treatment is going to
work, so it does. The placebo effect is also a factor to
some degree in clinically-effective therapies, and
explains why patients respond better than others to
treatment despite similar symptoms and illnesses.
Raynaud’s syndrome—A vascular, or circulatory
system, disorder which is characterized by abnormally cold hands and feet. This chilling effect is
caused by constriction of the blood vessels in the
extremities, and occurs when the hands and feet
are exposed to cold weather. Emotional stress can
also trigger the cold symptoms.
Schizophrenia—Schizophrenia is a psychotic disorder that causes distortions in perception (delusions and hallucinations), inappropriate moods
and behaviors, and disorganized or incoherent
speech and behavior.
Temporomandibular joint disorder—Inflammation,
irritation, and pain of the jaw caused by improper
opening and closing of the temporomandibular
joint. Other symptoms include clicking of the jaw
and a limited range of motion.

Recent research also indicates that biofeedback may
be a useful tool in helping patients with urinary incontinence regain bladder control. Individuals learning pelvic-floor muscle strengthening exercises can gain better
control over these muscles by using biofeedback. Sensors
are placed on the muscles to train the patient where they
are and when proper contractions are taking place.

Description
Origins
In 1961, Neal Miller, an experimental psychologist, suggested that autonomic nervous system
GALE ENCYCLOPEDIA OF MEDICINE

responses (for instance, heart rate, blood pressure,
gastrointestinal activity, regional blood flow) could
be under voluntary control. As a result of his experiments, he showed that such autonomic processes were
controllable. This work led to the creation of biofeedback therapy. Willer’s work was expanded by other
researchers. Thereafter, research performed in the
1970s by UCLA researcher Dr. Barry Sterman established that both cats and monkeys could be trained to
control their brain wave patterns. Sterman then used
his research techniques on human patients with epilepsy, where he was able to reduce seizures by 60%
with the use of biofeedback techniques. Throughout
the 1970s, other researchers published reports of their
use of biofeedback in the treatment of cardiac arrhythmias, headaches, Raynaud’s syndrome, and excess
stomach acid, and as a tool for teaching deep relaxation. Since the early work of Miller and Sterman,
biofeedback has developed into a front-line behavioral
treatment for an even wider range of disorders and
symptoms.
During biofeedback, special sensors are placed on
the body. These sensors measure the bodily function
that is causing the patient problem symptoms, such as
heart rate, blood pressure, muscle tension (EMG or
electromyographic feedback), brain waves (EEC or electroencophalographic feedback), respiration, and body
temperature (thermal feedback), and translates the
information into a visual and/or audible readout, such
as a paper tracing, a light display, or a series of beeps.
While the patient views the instantaneous feedback from the biofeedback monitors, he or she begins
to recognize what thoughts, fears, and mental images
influence his or her physical reactions. By monitoring this relationship between mind and body, the
patient can then use these same thoughts and mental
images as subtle cues, as these act as reminders to
become deeply relaxed, instead of anxious. These
reminders also work to manipulate heart beat, brain
wave patterns, body temperature, and other bodily
functions. This is achieved through relaxation exercises, mental imagery, and other cognitive therapy
techniques.
As the biofeedback response takes place, patients
can actually see or hear the results of their efforts
instantly through the sensor readout on the biofeedback equipment. Once these techniques are learned
and the patient is able to recognize the state of relaxation or visualization necessary to alleviate symptoms,
the biofeedback equipment itself is no longer needed.
The patient then has a powerful, portable, and selfadministered treatment tool to deal with problem
symptoms.
535

Biofeedback

KEY TERMS

Biofeedback

Biofeedback that specializes in reading and altering brain waves is sometimes called neurofeedback.
The brain produces four distinct types of brain
waves—delta, theta, alpha, and beta—that all operate
at a different frequency. Delta, the slowest frequency
wave, is the brain wave pattern associated with sleep.
Beta waves, which occur in a normal, waking state,
can range from 12-35 Hz. Problems begin to develop
when beta wave averages fall in the low end (underarousal) or the high end (overarousal) of that spectrum. Underarousal might be present in conditions
such as depression or attention-deficit disorder, and
overarousal may be indicative of an anxiety disorder,
obsessive compulsive disorder, or excessive stress.
Beta wave neurofeedback focuses on normalizing
that beta wave pattern to an optimum value of around
14 Hz. A second type of neurofeedback, alpha-theta,
focuses on developing the more relaxing alpha (8-13
Hz) and theta waves (4-9 Hz) that are usually associated with deep, meditative states, and has been used
with some success in substance abuse treatment.
Through brain wave manipulation, neurofeedback
can be useful in treating a variety of disorders that are
suspected or proven to impact brain wave patterns,
such as epilepsy, attention-deficit disorder, migraine
headaches, anxiety, depression, traumatic brain injury,
and sleep disorders. The equipment used for neurofeedback usually uses a monitor as an output device. The
monitor displays specific patterns that the patient
attempts to change by producing the appropriate type
of brain wave. Or, the monitor may reward the patient
for producing the appropriate brain wave by producing
a positive reinforcer, or reward. For example, children
may be rewarded with a series of successful moves in a
displayed video game.
Depending on the type of biofeedback, individuals
may need up to 30 sessions with a trained professional to
learn the techniques required to control their symptoms
on a long-term basis. Therapists usually recommend
that their patients practice both biofeedback and relaxation techniques on their own at home.

Preparations
Before initiating biofeedback treatment, the
therapist and patient will have an initial consultation
to record the patients medical history and treatment
background and discuss goals for therapy.
Before a neurofeedback session, an EEG is taken
from the patient to determine his or her baseline brainwave pattern.
Biofeedback typically is performed in a quiet and
relaxed atmosphere with comfortable seating for the
536

patient. Depending on the type and goals of biofeedback being performed, one or more sensors will be
attached to the patient’s body with conductive gel
and/or adhesives. These may include:


Electromyographic (EMG) sensors. EMG sensors
measure electrical activity in the muscles, specifically
muscle tension. In treating TMJ or bruxism, these
sensors would be placed along the muscles of the jaw.
Chronic pain might be treated by monitoring electrical energy in other muscle groups.



Galvanic skin response (GSR) sensors. These are
electrodes placed on the fingers that monitor perspiration, or sweat gland, activity. These may also
be called skin conductance level (SCL).



Temperature sensors. Temperature, or thermal, sensors measure body temperature and changes in blood
flow.



Electroencephalography (EEG) sensors. These electrodes are applied to the scalp to measure the electrical activity of the brain, or brain waves.



Heart rate sensors. A pulse monitor placed on the
finger tip can monitor pulse rate.



Respiratory sensors. Respiratory sensors monitor
oxygen intake and carbon dioxide output.

Precautions
Individuals who use a pacemaker or other implantable electrical devices should inform their biofeedback therapist before starting treatments, as certain
types of biofeedback sensors have the potential to
interfere with these devices.
Biofeedback may not be suitable for some
patients. Patients must be willing to take a very active
role in the treatment process. And because biofeedback focuses strictly on behavioral change, those
patients who wish to gain insight into their symptoms
by examining their past might be better served by
psychodynamic therapy.
Biofeedback may also be inappropriate for cognitively impaired individuals, such as those patients with
organic brain disease or a traumatic brain injury,
depending on their levels of functioning.
Patients with specific pain symptoms of unknown
origin should undergo a thorough medical examination before starting biofeedback treatments to rule out
any serious underlying disease. Once a diagnosis has
been made, biofeedback can be used concurrently with
conventional treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Side effects
There are no known side effects to properly administered biofeedback or neurofeedback sessions.

Research and general acceptance
Preliminary research published in late 1999 indicated that neurofeedback may be a promising new tool
in the treatment of schizophrenia. Researchers
reported that schizophrenic patients had used neurofeedback to simulate brain wave patterns that antipsychotic medications produce in the brain. Further
research is needed to determine what impact this may
have on treatment for schizophrenia.
The use of biofeedback techniques to treat an array
of disorders has been extensively described in the medical literature. Controlled studies for some applications
are limited, such as for the treatment of menopausal
symptoms and premenstrual disorder (PMS). There is
also some debate over the effectiveness of biofeedback
in ADHD treatment, and the lack of controlled studies
on that application. While many therapists, counselors,
and mental health professionals have reported great
success with treating their ADHD patients with neurofeedback techniques, some critics attribute this positive
therapeutic impact to a placebo effect.
There may also be some debate among mental
health professionals as to whether biofeedback should
be considered a first line treatment for some mental
illnesses, and to what degree other treatments, such as
medication, should be employed as an adjunct therapy.
Resources
BOOKS

Robbins, Jim. A Symphony in the Brain: The Evolution of the
New Brain Wave Biofeedback. Boston, MA: Atlantic
Monthly Press, 2000.
PERIODICALS

Robbins, Jim. ‘‘On the Track with Neurofeedback.’’
Newsweek 135, no. 25 (June 2000): 76.
ORGANIZATIONS

Association for Applied Psychotherapy and Biofeedback.
10200 W. 44th Avenue, Suite 304, Wheat Ridge, CO
80033-2840. (303) 422-8436. <http://www.aapb.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Biofeedback Certification Institute of America.10200 W.
44th Avenue, Suite 310, Wheat Ridge, CO 80033. (303)
420-2902.

Paula Anne Ford-Martin

Biopsy see Bone biopsy; Bone marrow
aspiration and biopsy; Brain biopsy;
Breast biopsy; Cervical conization; CTguided biopsy; Endometrial biopsy; Joint
biopsy; Kidney biopsy; Liver biopsy; Lung
biopsy; Lymph node biopsy; Myocardial
biopsy; Pleural biopsy; Prostate biopsy;
Skin biopsy; Small intestine biopsy;
Thyroid biopsy

I Bipolar disorder
Definition
Bipolar, or manic-depressive disorder, is a mood
disorder that causes radical emotional changes and
mood swings, from manic highs to depressive lows.
The majority of bipolar individuals experience alternating episodes of mania and depression.

Description
In the United States alone, more than two million
people are diagnosed with bipolar disorder. Research
shows that as many as 10 million people might be
affected by bipolar disorder, which is the sixth-leading
cause of disability worldwide. The average age of
onset of bipolar disorder is from adolescence through
the early twenties. However, because of the complexity
of the disorder, a correct diagnosis can be delayed for
several years or more. In a survey of bipolar patients
conducted by the National Depressive and Manic
Depressive Association (MDMDA), one-half of
respondents reported visiting three or more professionals before receiving a correct diagnosis, and over
one-third reported a wait of ten years or more before
they were correctly diagnosed.
Bipolar I disorder is characterized by manic episodes, the ‘‘high’’ of the manic-depressive cycle. A
person with bipolar disorder experiencing mania often
has feelings of self-importance, elation, talkativeness,
increased sociability, and a desire to embark on goaloriented activities, coupled with the characteristics of
irritability, impatience, impulsiveness, hyperactivity,
537

Bipolar disorder

Biofeedback may only be one component of a
comprehensive treatment plan. For illnesses and
symptoms that are manifested from an organic disease
process, such as cancer or diabetes, biofeedback
should be an adjunct to (complementary to), and not
a replacement for, conventional medical treatment.

Bipolar disorder

KEY TERMS
Affective disorder—An emotional disorder involving abnormal highs and/or lows in mood. Now
termed mood disorder.
Anticonvulsant medication—A drug used to prevent convulsions or seizures; often prescribed in
the treatment of epilepsy. Several anticonvulsant
medications have been found effective in the treatment of bipolar disorder.
Antipsychotic medication—A drug used to treat
psychotic symptoms, such as delusions or hallucinations, in which patients are unable to distinguish
fantasy from reality.
Benzodiazpines—A group of tranquilizers having
sedative, hypnotic, antianxiety, amnestic, anticonvulsant, and muscle relaxant effects.
DSM-IV—Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV). This
reference book, published by the American
Psychiatric Association, is the diagnostic standard
for most mental health professionals in the United
States.
ECT—Electroconvulsive therapy sometimes is used
to treat depression or mania when pharmaceutical
treatment fails.
Hypomania—A milder form of mania which is
characteristic of bipolar II disorder.
Mixed mania/mixed state—A mental state in
which symptoms of both depression and mania
occur simultaneously.
Mania—An elevated or euphoric mood or irritable
state that is characteristic of bipolar I disorder.
Neurotransmitter—A chemical in the brain that
transmits messages between neurons, or nerve
cells. Changes in the levels of certain neurotransmitters, such as serotonin, norepinephrine, and
dopamine, are thought to be related to bipolar
disorder.
Psychomotor retardation—Slowed mental and
physical processes characteristic of a bipolar
depressive episode.

and a decreased need for sleep. Usually this manic
period is followed by a period of depression, although
a few bipolar I individuals may not experience a major
depressive episode. Mixed states, where both manic or
hypomanic symptoms and depressive symptoms occur
at the same time, also occur frequently with bipolar I
538

patients (for example, depression with the racing
thoughts of mania). Also, dysphoric mania is common
(mania characterized by anger and irritability).
Bipolar II disorder is characterized by major
depressive episodes alternating with episodes of hypomania, a milder form of mania. Bipolar depression
may be difficult to distinguish from a unipolar major
depressive episode. Patients with bipolar depression
tend to have extremely low energy, retarded mental
and physical processes, and more profound fatigue
(for example, hypersomnia; a sleep disorder marked
by a need for excessive sleep or sleepiness when awake)
than unipolar depressives.
Cyclothymia refers to the cycling of hypomanic
episodes with depression that does not reach major
depressive proportions. One-third of patients with
cyclothymia will develop bipolar I or II disorder
later in life.
A phenomenon known as rapid cycling occurs in
up to 20% of bipolar I and II patients. In rapid cycling,
manic and depressive episodesmust alternate frequently;
at least four times in 12 months; to meet the diagnostic
definition. In some cases of ‘‘ultra-rapid cycling,’’ the
patient may bounce between manic and depressive
states several times within a 24-hour period. This condition is very hard to distinguish from mixed states.
Bipolar NOS is a category for bipolar states that
do not clearly fit into the bipolar I, II, or cyclothymia
diagnoses.

Causes and symptoms
The source of bipolar disorder has not been
clearly defined. Because two-thirds of bipolar patients
have a family history of affective or emotional disorders, researchers have searched for a genetic link to the
disorder. Several studies have uncovered a number of
possible genetic connections to the predisposition for
bipolar disorder. A 2003 study found that schizophrenia and bipolar disorder could have similar genetic
causes that arise from certain problems with genes
associated with myelin development in the central
nervous system. (Myelin is a white, fat-like substance
that forms a sort of layer or sheath around nerve
fibers.) Another possible biological cause under investigation is the presence of an excessive calcium buildup in the cells of bipolar patients. Also, dopamine and
other neurochemical transmitters appear to be implicated in bipolar disorder and these are under intense
investigation.
Over one-half of patients diagnosed with bipolar
disorder have a history of substance abuse. There is a
GALE ENCYCLOPEDIA OF MEDICINE

For some bipolar patients, manic and depressive
episodes coincide with seasonal changes. Depressive
episodes are typical during winter and fall, and
manic episodes are more probable in the spring and
summer months.
Symptoms of bipolar depressive episodes include
low energy levels, feelings of despair, difficulty concentrating, extreme fatigue, and psychomotor retardation (slowed mental and physical capabilities). Manic
episodes are characterized by feelings of euphoria,
lack of inhibitions, racing thoughts, diminished need
for sleep, talkativeness, risk taking, and irritability. In
extreme cases, mania can induce hallucinations and
other psychotic symptoms such as grandiose illusions.

Diagnosis
Bipolar disorder usually is diagnosed and treated
by a psychiatrist and/or a psychologist with medical
assistance. In addition to an interview, several clinical
inventories or scales may be used to assess the patient’s
mental status and determine the presence of bipolar
symptoms. These include the Millon Clinical
Multiaxial Inventory III (MCMI-III), Minnesota
Multiphasic Personality Inventory II (MMPI-2), the
Internal State Scale (ISS), the Self-Report Manic
Inventory (SRMI), and the Young Mania Rating
Scale (YMRS). The tests are verbal and/or written
and are administered in both hospital and outpatient
settings.
Psychologists and psychiatrists typically use the
criteria listed in the Diagnostic and Statistical Manual
of Mental Disorders, Fourth Edition (DSM-IV ) as
a guideline for diagnosis of bipolar disorder and
other mental illnesses. DSM-IV describes a manic
episode as an abnormally elevated or irritable mood
lasting a period of at least one week that is distinguished
by at least three of the mania symptoms: inflated selfesteem, decreased need for sleep, talkativeness, racing
thoughts, distractibility, increase in goal-directed activity, or excessive involvement in pleasurable activities
that have a high potential for painful consequences. If
the mood of the patient is irritable and not elevated,
four of the symptoms are required.
Although many clinicians find the criteria too
rigid, a hypomanic diagnosis requires a duration
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of at least four days with at least three of the symptoms
indicated for manic episodes (four if mood is irritable
and not elevated). DSM-IV notes that unlike manic
episodes, hypomanic episodes do not cause a marked
impairment in social or occupational functioning, do
not require hospitalization, and do not have psychotic
features. In addition, because hypomanic episodes are
characterized by high energy and goal directed activities and often result in a positive outcome, or are
perceived in a positive manner by the patient, bipolar
II disorder can go undiagnosed.
Bipolar symptoms often present differently in
children and adolescents. Manic episodes in these age
groups are typically characterized by more psychotic
features than in adults, which may lead to a misdiagnosis of schizophrenia. Children and adolescents also
tend toward irritability and aggressiveness instead of
elation. Further, symptoms tend to be chronic, or
ongoing, rather than acute, or episodic. Bipolar children are easily distracted, impulsive, and hyperactive,
which can lead to a misdiagnosis of attention deficit
hyperactivity disorder (ADHD). Furthermore, their
aggression often leads to violence, which may be misdiagnosed as a conduct disorder.
Substance abuse, thyroid disease, and use of
prescription or over-the-counter medication can mask
or mimic the presence of bipolar disorder. In cases of
substance abuse, the patient must ordinarily undergo a
period of detoxification and abstinence before a mood
disorder is diagnosed and treatment begins.

Treatment
Treatment of bipolar disorder is usually achieved
with medication. A combination of mood stabilizing
agents with antidepressants, antipsychotics, and anticonvulsants is used to regulate manic and depressive
episodes.
Mood stabilizing agents such as lithium, carbamazepine, and valproate are prescribed to regulate the
manic highs and lows of bipolar disorder:


Lithium (Cibalith-S, Eskalith, Lithane, Lithobid,
Lithonate, Lithotabs) is one of the oldest and most
frequently prescribed drugs available for the treatment of bipolar mania and depression. Because the
drug takes four to ten days to reach a therapeutic
level in the bloodstream, it sometimes is prescribed in
conjunction with neuroleptics and/or benzodiazepines to provide more immediate relief of a manic
episode. Lithium also has been shown to be effective
in regulating bipolar depression, but is not recommended for mixed mania. Lithium may not be an
539

Bipolar disorder

high rate of association between cocaine abuse and
bipolar disorder. Some studies have shown up to 30%
of abusers meeting the criteria for bipolar disorder. The
emotional and physical highs and lows of cocaine use
correspond to the manic depression of the bipolar
patient, making the disorder difficult to diagnosis.

Bipolar disorder

effective long-term treatment option for rapid cyclers,
who typically develop a tolerance for it, or may not
respond to it. Possible side effects of the drug include
weight gain, thirst, nausea, and hand tremors.
Prolonged lithium use also may cause hyperthyroidism (a disease of the thryoid that is marked by heart
palpitations, nervousness, the presence of goiter,
sweating, and a wide array of other symptoms.)




Carbamazepine (Tegretol, Atretol) is an anticonvulsant drug usually prescribed in conjunction with
other mood stabilizing agents. The drug often is
used to treat bipolar patients who have not
responded well to lithium therapy. Blurred vision
and abnormal eye movement are two possible side
effects of carbamazepine therapy.

system. Patients taking MAOIs must cut foods high
in tyramine (found in aged cheeses and meats) out of
their diet to avoid hypotensive side effects.


Bupropion (Wellbutrin) is a heterocyclic antidepressant. The exact neurochemical mechanism of the
drug is not known, but it has been effective in regulating bipolar depression in some patients. Side
effects of bupropion include agitation, anxiety, confusion, tremor, dry mouth, fast or irregular heartbeat,
headache, and insomnia.



ECT, or electroconvulsive therapy, has a high success
rate for treating both unipolar and bipolar depression, and mania. However, because of the convenience of drug treatment and the stigma sometimes
attached to ECT therapy, ECT usually is employed
after all pharmaceutical treatment options have been
explored. ECT is given under anesthesia and patients
are given a muscle relaxant medication to prevent
convulsions. The treatment consists of a series of
electrical pulses that move into the brain through
electrodes on the patient’s head. Although the exact
mechanisms behind the success of ECT therapy are
not known, it is believed that this electrical current
alters the electrochemical processes of the brain, consequently relieving depression. Headaches, muscle
soreness, nausea, and confusion are possible side
effects immediately following an ECT procedure.
Temporary memory loss has also been reported in
ECT patients. In bipolar patients, ECT is often used
in conjunction with drug therapy.

Valproate (divalproex sodium, or Depakote; valproic
acid, or Depakene) is one of the few drugs available
that has been proven effective in treating rapid cycling
bipolar and mixed states patients. Valproate is prescribed alone or in combination with carbamazepine
and/or lithium. Stomach cramps, indigestion, diarrhea, hair loss, appetite loss, nausea, and unusual
weight loss or gain are some of the common side
effects of valproate. Note: valproate also is approved
for the treatment of mania. A 2003 study found that
the risk of death from suicide is about two and onehalf times higher in people with bipolar disorder
taking divalproex than those taking lithium.

Treating the depression associated with bipolar
disorder has proven more challenging. In early 2004,
the first drug to treat bipolar administration was
approved by the U.S. Food and Drug Administration
(FDA). It is called Symbyax, a combination of olanzipine and fluoxetine, the active ingredient in Prozac.
Because antidepressants may stimulate manic
episodes in some bipolar patients, their use typically
is short-term. Selective serotonin reuptake inhibitors
(SSRIs) or, less often, monoamine oxidase inhibitors
(MAO inhibitors) are prescribed for episodes of bipolar depression. Tricyclic antidepressants used to treat
unipolar depression may trigger rapid cycling in bipolar patients and are, therefore, not a preferred treatment option for bipolar depression.


SSRIs, such as fluoxetine (Prozac), sertraline
(Zoloft), and paroxetine (Paxil), regulate depression
by regulating levels of serotonin, a neurotransmitter.
Anxiety, diarrhea, drowsiness, headache, sweating,
nausea, sexual problems, and insomnia are all possible side effects of SSRIs.



MAOIs such as tranylcypromine (Parnate) and phenelzine (Nardil) block the action of monoamine oxidase (MAO), an enzyme in the central nervous

540

Adjunct treatments are used in conjunction with
a long-term pharmaceutical treatment plan:


Long-acting benzodiazepines such as clonazepam
(Klonapin) and alprazolam (Xanax) are used for
rapid treatment of manic symptoms to calm and
sedate patients until mania or hypomania have
waned and mood stabilizing agents can take effect.
Sedation is a common effect, and clumsiness, lightheadedness, and slurred speech are other possible
side effects of benzodiazepines.



Neuroleptics such as chlorpromazine (Thorazine) and
haloperidol (Haldol) also are used to control mania
while a mood stabilizer such as lithium or valproate
takes effect. Because neuroleptic side effects can be
severe (difficulty in speaking or swallowing, paralysis
of the eyes, loss of balance control, muscle spasms,
severe restlessness, stiffness of arms and legs, tremors
in fingers and hands, twisting movements of body,
and weakness of arms and legs), benzodiazepines are
generally preferred over neuroleptics.



Psychotherapy and counseling. Because bipolar disorder is thought to be biological in nature, therapy is
GALE ENCYCLOPEDIA OF MEDICINE

Clozapine (Clozaril) is an atypical antipsychotic
medication used to control manic episodes in patients
who have not responded to typical mood stabilizing
agents. The drug has also been a useful prophylactic,
or preventative treatment, in some bipolar patients.
Common side effects of clozapine include tachycardia
(rapid heart rate), hypotension, constipation, and
weight gain. Agranulocytosis, a potentially serious but
reversible condition in which the white blood cells that
typically fight infection in the body are destroyed, is a
possible side effect of clozapine. Patients treated with
the drug should undergo weekly blood tests to monitor
white blood cell counts.
Risperidone (Risperdal) is an atypical antipsychotic medication that has been successful in controlling
mania when low doses were administered. In early
2004, the FDA approved its use for treating bipolar
mania. The side effects of risperidone are mild compared to many other antipsychotics (constipation,
coughing, diarrhea, dry mouth, headache, heartburn,
increased length of sleep and dream activity, nausea,
runny nose, sore throat, fatigue, and weight gain).
Olanzapine (Zyprexa) is another atypical antipsychotic approved in 2003 for use in combination with
lithium or valproate for treatment of acute manic
episodes associated with bipolar disorder. Side effects
include hypotension (low blood pressure) associated
with dizziness, rapid heartbeat, and syncope, or low
blood pressure to the point of fainting.
Lamotrigine (Lamictal, or LTG), an anticonvulsant medication, was found to alleviate manic symptoms in a 1997 trial of 75 bipolar patients. The drug
was used in conjunction with divalproex (divalproate)
and/or lithium. Possible side effects of lamotrigine
include skin rash, dizziness, drowsiness, headache,
nausea, and vomiting.

plenty of rest, regular exercise, and proper diet.
Chinese herbs may soften mood swings. Biofeedback
is effective in helping some patients control symptoms
such as irritability, poor self control, racing thoughts,
and sleep problems. A diet low in vanadium (a mineral
found in meats and other foods) and high in vitamin C
may be helpful in reducing depression.
A surprising study in 2004 found that a rarely used
combination of magnetic fields used in magnetic resonance imaging (MRI) scanning improved the moods of
subjects with bipolar disorder. The discovery was
made while scientists were using MRI to investigate
effectiveness of certain medications. However, they
found that a particular type of echo-planar magnetic
field led to reports of mood improvement. Further
studies may one day lead to a smaller, more convenient use of magnetic treatment.

Prognosis
While most patients will show some positive
response to treatment, response varies widely, from
full recovery to a complete lack of response to all
drug and/or ECT therapy. Drug therapies frequently
need adjustment to achieve the maximum benefit for
the patient. Bipolar disorder is a chronic recurrent
illness in over 90% of those afflicted, and one that
requires lifelong observation and treatment after diagnosis. Patients with untreated or inadequately treated
bipolar disorder have a suicide rate of 15-25% and a
nine-year decrease in life expectancy. With proper
treatment, the life expectancy of the bipolar patient
will increase by nearly seven years and work productivity increases by ten years.

Prevention
The ongoing medical management of bipolar disorder is critical to preventing relapse, or recurrence, of
manic episodes. Even in carefully controlled treatment
programs, bipolar patients may experience recurring
episodes of the disorder. Patient education in the form
of psychotherapy or self-help groups is crucial for
training bipolar patients to recognize signs of mania
and depression and to take an active part in their
treatment program.
Resources
PERIODICALS

Alternative treatment
General recommendations include maintaining a
calm environment, avoiding overstimulation, getting
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Family-focused Therapy May Reduce Relapse Rate.’’
Health & Medicine Week (September 29, 2003): 70.
‘‘FDA Approves Medication for Bipolar Depression.’’ Drug
Week (January 23, 2004): 320.
541

Bipolar disorder

recommended as a companion to, but not a substitute for, pharmaceutical treatment of the disease.
Psychotherapy, such as cognitive-behavioral therapy,
can be a useful tool in helping patients and their
families adjust to the disorder, in encouraging compliance to a medication regimen, and in reducing the
risk of suicide. Also, educative counseling is recommended for the patient and family. In fact, a 2003
report revealed that people on medication for bipolar
disorder had better results if they also participated in
family-focused therapy.

Bird flu

‘‘FDA Approves Risperidone for Bipolar Mania.’’
Psychopharmacology Update (January 2004): 8.
‘‘Lithium and Risk of Suicide.’’ The Lancet (September 20,
2003): 969.
Rossiter, Brian. ‘‘Bipolar Disorder.’’ Med Ad News (March
2004): 82.
‘‘Schizophrenia and Bipolar Disorder Could Have Similar
Genetic Causes.’’ Genomics & Genetics Weekly
(September 26, 2003): 85.
Sherman, Carl. ‘‘Bipolar’s Clinical, Financial Impact Widely
Missed. (Prevalence May be Greater Than Expected).’’
Clinical Psychiatry News (August 2002): 6.
‘‘Unique Type of MRI Scan Shows Promise in Treating
Bipolar Disorder.’’ AScribe Health News Service
(January 1, 2004).
‘‘Zyprexa.’’ Formulary 9 (September 2003): 513.
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington,
VA 22201-3042. (800) 950-6264. <http://
www.nami.org>.
National Depressive and Manic-Depressive Association
(NDMDA). 730 N. Franklin St., Suite 501, Chicago,
IL 60610. (800) 826-3632. <http://
www.ndmda.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Paula Anne Ford-Martin
Teresa G. Odle

pheasants, quail, and guinea fowl. The avian influenza
viruses generally do not infect humans.
Avian viruses are carried around the world by
migratory birds. Wild ducks are natural reservoirs of
the infection, according to the World Health
Organization (WHO). Those wild birds generally
don’t become ill, but avian flu is extremely contagious
and has caused some domesticated birds to become
very ill and die. The casualties included chickens, turkeys, and ducks.
Virus suptypes
Reaction to the infection varies among the species
because flu viruses are constantly mutating into new
strains or subgroups. Low-pathogenic viruses cause
few or no symptoms in infected birds. However,
some strains can mutate into highly pathogenic avian
influenza (HPAI) strains that are extremely infectious
and deadly to birds.
The viruses are identified by a series of letters and
numbers that refer to two proteins, hemagglutinin
(HA) and neuraminidase (NA). There are 16 HA subtypes and nine NA subtypes of influenza A virus.
Numerous combinations of the two proteins are
possible, and each combination forms a new subtype.
There are 15 different Influenza A subtypes that
can infect birds, according to the United States
Centers for Disease Control (CDC). In comparison,
there are three known subtypes of human flu virus A:
H1N1, H1N2, and H3N2. Avian viruses can infect
pigs, but people are generally not affected. That changed when there was an outbreak of H5N1 in Hong
Kong in 1997.
Deadly outbreaks

I Bird flu
Definition
Bird flu is an infectious disease caused by strains
of the Type A influenza viruses that ordinarily only
infect birds. Avian influenza A (H5N1) virus infected
and caused the deaths of people.

Description
Bird flu, which is also known as avian influenza,
was first identified in Italy more than 100 years ago.
Avian viruses occur naturally in birds, and can infect
birds including chickens, ducks, geese, turkeys,
542

The highly pathogenic H5N1 virus was first isolated
in terns in South Africa in 1961, and then in Hong Kong
in 1997. Hong Kong’s avian flu outbreak coincided
with 18 cases of severe respiratory disease in people.
Those diagnosed with bird flu had close contact with
poultry. Six people died, according to WHO. There
was ‘‘limited transmission’’ of the virus to health care
workers, but they did not become seriously ill.
Medical research showed that the avian virus had
jumped from birds to people. Within three days, Hong
Kong’s poultry population of about 1.5 million birds
was destroyed to prevent further infection. There was
another H5N1 outbreak in Hong Kong in February
of 2003. It affected two members of a family that had
recently visited China. One person died, according to
the WHO.
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In Hong Kong, the avian virus subtype H9N2
caused mild cases of flu in two children in 1999 and
one child in the middle of December of 2003, according to WHO. While H9N2 was not highly pathogenic
in birds, there was an outbreak of H5N1 in Korea in
mid-December of 2003. The next month, there was an
outbreak in Vietnam that was followed by outbreaks
in other Asian countries.
Human bird flu cases
The World Health Organization tracks bird flu outbreaks and the charts the numbers of human cases that
have been confirmed by a laboratory. There were 74
cases and 49 deaths between January of 2004 and March
31, 2005. The flu caused two deaths in Cambodia. In
Thailand, 12 of 17 people with bird flu died. In Vietnam,
the flu was fatal in 35 of 55 diagnosed cases. Deaths
related to the H5N1 viruses have been caused by pneumonia and pulmonary complications.
Moreover, the Democratic People’s Republic of
Korea (North Korea) officially reported the country’s
first outbreak of avian influenza in poultry on March 27,
2005. Outbreaks occurred at chicken farms, and there
were no human cases at that time, according to WHO.
In October 2005, an outbreak of bird flu was
reported at a farm near the Mongolian capital of
Hohhot in the People’s Republic of China. The H5N1
strain of the virus was detected in a parrot located in
Britain. The parrot contracted the disease while in quarantine with birds originating in Taiwan. In January 2006,
the H5N1 strain was confirmed as the cause of death in at
least two cases in Dogubeyazit, Turkey. This case, as well
as others documented in countries across Europe, indicate the potential for the disease to spread worldwide.
Preparing for a pandemic

the new virus strain. Historically, pandemics occur
three to four times during a century when new virus
subtypes appear. After World War I, the great influenza pandemic of 1917-1918 caused from 40 to 50
million deaths globally, according to WHO. The flu
pandemic of 1968-1969 claimed 1 to 4 million lives.
According to a 2004 WHO report, medical influenza experts agree that another flu pandemic is ‘‘inevitable and possibly imminent.’’ In a December 8, 2004
report, WHO warned that the ‘‘best case scenario’’
projection for next pandemic was that the new flu strain
would kill from 2 to 7 million people. Moreover, ‘‘tens
of millions’’ of people would require medical attention.
The appearance of H5N1 signals that the world is
moving closer to a pandemic, WHO reported.
The spread of H5N1 to humans increased the
likelihood of a new strain emerging that could be
transmitted by people. That could create a pandemic.
Nations and the World Health Organization are
working to prevent a pandemic or cause it to be less
deadly. Their strategies include efforts to decrease the
spread of flu strains in poultry and the development of
vaccines to treat the virus in people.

Causes and symptoms
Avian flu is caused by an influenza virus that birds
carry in their intestines. The virus spreads as infected
birds excrete saliva, nasal secretions, and feces. Birds
vulnerable to the flu become infected when they come
into contact with the excretions or surfaces contaminated by the infected matter.
Birds that survive the H5N1 infection can
excrete the virus for at least 10 days, according to a
WHO report. The strain had proliferated through
bird-to-bird contact to flocks on farms and poultry
in live bird markets. The virus can also spread in
surfaces including manure, bird feed, equipment,
vehicles, egg flats, and crates, and the clothing and
shoes of people who came into contact with the
virus.

The World Health Organization and nations
including the United States are troubled about the
deadly consequences that could occur if H5N1 mutated
into a new virus subtype that could be transferred from
one human to another. That subtype would develop if
the avian virus acquired human influenza genes,
according to the U.S. Department of Agriculture
(USDA). A strain of bird flu spread by human-tohuman contact could cause an influenza pandemic.

A small amount of a highly pathogenic avian
influenza virus could be deadly. One gram (0.035
ounces) of contaminated manure could hold enough
virus to infect 1 million birds, according to the USDA.
From 1997 through the spring of 2005, the viruses
primarily infected people in Asia who had contact
with infected birds and surfaces.

A pandemic is a worldwide epidemic that is dangerous because people have little or no immunity to

In early 2005, information about symptoms of
H5N1 in humans was based on the 1997 Hong Kong

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Bird flu symptoms in people

543

Bird flu

In the Netherlands in February of 2003, there was
an outbreak of another highly pathogenic avian virus,
H7N7. Two months later, a veterinarian died from the
virus. It also caused mild illness in 83 people.

Bird flu

outbreak. People experienced traditional flu symptoms
such as a fever, cough, sore throat, and aching muscles.
Other symptoms included eye infections (conjunctivitis), pneumonia, acute respiratory distress, viral pneumonia, and other severe and life-threatening
complications.
Avian flu symptoms in birds
The sudden death of a bird that had not appeared
ill is one symptom of the highly pathogenic bird flu.
According to the USDA, infected live birds may display one or more of the following symptoms: lack
of energy, appetite loss, nasal discharge, coughing,
sneezing, a lack of coordination, and diarrhea. In
addition, the bird may lay fewer eggs or produce eggs
that are soft-shelled or misshapen. Furthermore, there
may be swelling of the head, eyelids, comb, and wattles. Another symptom is purple discoloration on the
combs, wattles, and legs.
If there is an outbreak of the highly pathogenic
flu in birds, they are destroyed to prevent the spread of
the virus.
Virus mixing vessels
Influenza viruses undergo frequent changes and
form new subtypes. In addition, influenza A viruses
can trade genetic materials with the viruses of other
species. Two different strains trade or merge material,
a process known as an antigenic shift. That shift produces a new subtype that is different from the two
parent viruses. When the new subtype contains genes
from the human virus, a pandemic resulted because
there was no immunity to the virus and no vaccine to
protect against it.
The genetic shift occurs in a ‘‘mixing vessel’’ that
was susceptible to both types of flu. In the past, the
shift was thought to be related to people living close to
pigs and domestic poultry. Pigs can be infected by
avian viruses and mammalian viruses like the human
strains, according to WHO. However, research into
the H5N1 strain indicates that people can serve as the
mixing vessels. As more people become infected with
bird flu, the probability increases that humans would
serve as the mixing vessel for a new subtype that could
be transmitted from one person to another.

Diagnosis
The symptoms of avian flu and human flu are very
similar, so laboratory testing is needed to diagnose
avian influenza. In addition to diagnosing the individual, testing in 2005 was performed to determine
544

whether the infection was spreading from birds to
people or from humans to humans.
Diagnostic tests for human flu are rapid and reliable, according to WHO. The international organization noted that laboratories within WHO’s global
network have high-security facilities and experienced
staff. Test methods include a viral culture that analyses a blood sample and swabbings of the nose or
throat. Other testing examines respiratory secretions.
In the United States, the Centers for Disease
Control is among the organizations preparing for a
possible outbreak of bird flu in humans. In addition to
specifics related to diagnosing bird flu, CDC refers
healthcare workers to precautions to prevent the
spread of flu and other respiratory infections in medical settings.
Precautionary measures include directing people
to observe cough etiquette. People with symptoms of
respiratory infection should cover their mouths or use
facial tissues when coughing or sneezing. After coughing or sneezing, the person should wash their hands
with a non-antimicrobial soap and water, alcoholbased hand rub, or antiseptic handwash.
Furthermore, people with flu-like symptoms may
be given masks to wear while they are waiting to be
examined by medical personnel. The healthcare workers should wear masks in some circumstances.
Undoubtedly, they will wear masks when working
with people with symptoms of bird flu.

Treatment
As of March of 2005, there was no vaccine to
protect people from the H5N1 virus, according to the
CDC. However, the U.S. agency and the World
Health Organization had isolated seed strains of the
virus in order to make a vaccine. Safety tests were
scheduled to start in April of 2005 on a vaccine manufactured by Sanofi pasteur, a firm in Swiftwater,
Pennsylvania, formerly known as Aventis Pasteur.
On March 23, 2005, the National Institute of
Allergy and Infectious Diseases (NIAID) announced
that fast-track recruitment had started for volunteers
to participate in an investigative study of the vaccine.
During the Phase I trial, the trial vaccine will be tested
on 450 healthy adults between the ages of 18 to 64,
according to NIAID, which is part of the National
Institutes of Health.
Studies were to be conducted at University of
California at Los Angeles, University of Maryland
School of Medicine in Baltimore, and the University
of Rochester School of Medicine and Dentistry,
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Furthermore, research was underway on a vaccine
to fight H9N2, another avian flu virus subtype.
Treatment with existing drugs
Existing anti-viral medications may sometimes be
effective against avian flu viruses, according to a
March 18, 2005, report from CDC. In the United
States, four drugs have been approved by the U.S.
Food and Drug Administration (FDA) for the treatment and prevention of influenza A viruses.
The medications amantadine (Symmetrel),
rimantadine (Flumadine), seltamivir (Tamiflu), and
zanamivir (Relenza) were clinically effective in the
treatment of influenza A viruses in otherwise healthy
adults.
However, avian flu research indicated that the
H5N1 virus was resistant to amantadine and rimantadine, according to CCDC. The other two drugs would
‘‘probably work,’’ according to CDC. However, studies were needed of the medication’s effectiveness.
During the 2004 human flu season in the United
States, the Associated Press reported that Relenza cost
about $55 for the typical 10-day treatment. Tamiflu
cost approximately $66 for the same course of treatment. Insurance frequently covered part of the prescription costs.
For people diagnosed with bird flu, the World
Health Organization recommends that patients take
Tamiflu twice daily for five days. Treatment should
begin as soon as possible. Patients may also receive
medication to lower fevers and antibiotics to fight
secondary infections.
In the spring of 2005, there was no H5N1 vaccine.
Countries including the United States were reportedly
stockpiling Tamiflu in the event a pandemic erupted.
At that time, WHO and CDC recommended the issuing of anti-viral medication as a preventive measure to
people working in poultry production. Those people,
along with health care workers, would have priority
for the medications.

Alternative treatment
In March of 2005, people in South Korea began
eating more kimchi to ward off avian flu infection,
according to the reports from the British Broadcasting
Company and other news organizations. The public
turned to the spicy vegetable dish after scientists at
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Seoul National University announced that kimchi
aided in the recovery of 11 out of 13 infected chickens.
The scientists fed the birds an extract of kimchi, a dish
made by fermenting cabbage with red peppers,
radishes, and large amounts of garlic and ginger. A
week later, all but two birds showed signs of recovery.
The researchers acknowledged that their study
was unscientific. At that time, they were not sure
how or why kimchi was related to the recovery.
However, the announcement led people to again
regard kimchi as a health remedy. In 2003, interest in
kimchi increased when people thought eating it helped
prevent SARS (severe acute respiratory syndrome).
No scientific confirmation was made between kimchi
and SARS prevention.

Prognosis
Bird flu has been fatal to people, and there was
concern in 2005 about the virus mutating into a strain
that could be transmitted by people. Health organizations and government agencies focused on preventing or reducing the risks of a pandemic caused
by bird flu.
In the United States, research was underway on
vaccines to fight the flu. Other efforts include the
USDA Safety’s guidelines for people working with
poultry. Strategies included trade restrictions on poultry and poultry products from Asia, according to the
USDA. Imported live birds and eggs were quarantined
for 30 days. During that time, they were tested for bird
flu and exotic Newcastle disease. The United States
bans the import of poultry meat from Asia because
meat processing plants were not approved by the
USDA’s Food Safety and Inspection Service.

Prevention
In the spring of 2005, bird flu was primarily a risk
for people in the United States who worked with
poultry. Potentially vulnerable people included those
working with poultry on farms and avian health workers like veterinarians. People working with birds in
locations such as commercial poultry facilities, veterinary offices, and live bird markets should wear protective clothing. That equipment includes boots,
coveralls, face masks, gloves, and headgear, according
to the USDA. If necessary, they should receive antiviral medications as a safeguard.
Furthermore, poultry producers should implement security measures to prevent the outbreak of a
highly pathogenic virus. Those actions include keeping flocks away from wild or migratory birds and
545

Bird flu

Rochester, New York. If the vaccine is proven safe for
adults, there were plans to test it in people in other age
groups such as children and the elderly.

Birth defects

providing clothing and disinfectant facilities for
employees. Plastic crates should be used at live bird
markets because they were easier to clean than wood
crates. Cleaning and disinfecting areas were also
important for preventing an outbreak.
If necessary birds would be quarantined or
destroyed.

I Birth defects
Definition
Birth defects are physical abnormalities that are
present at birth; they also are called congenital
abnormalities. More than 3,000 have been identified.

Resources

Description

PERIODICALS

Associated Press. ‘‘Bird Flu Called Global Human Threat:
Asia Outbreak Poses ‘Gravest Possible Danger,’ U.N.
Official Says, Urging Controls.’’ Washington Post.
February 24, 2005 [cited March 30, 2005] <http://
www.washingtonpost.com/wp-dyn/articles/A464242005Feb23.html >.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Road, Atlanta, GA 30333. 800-CDC-INFO (2325636).<http://www.cdc.gov>.
National Institute of Allergy and Infectious Diseases. 6610
Rockledge Drive, MSC 6612, Bethesda, MD 208926612. 301-496-5717. <http://www.niaid.nih.gov>.
World Health Organization. Regional Office for the
Americas. 525, 23rd Street NW, Washington, DC
20037. 202-974-3000.<http://www.who>.
Highly Pathogenic Avian Influenza. United States
Department of Agriculture Animal and Plant
Inspection Safety. March 2004 [Cited March 31, 2005].
<http://www.aphis.usda.gov/lpa/pubs/fsheet_faq_
notice/fs_ahavianflu.html>.

Birth defects are found in 2-3% of all newborn
infants. This rate doubles in the first year, and reaches
10% by age five, as more defects become evident and
can be diagnosed. Almost 20% of deaths in newborns
are caused by birth defects.
Abnormalities can occur in any major organ or
part of the body. Major defects are structural abnormalities that affect the way a person looks and require
medical and/or surgical treatment. Minor defects are
abnormalities that do not cause serious health or social
problems. When multiple birth defects occur together
and have a similar cause, they are called syndromes. If
two or more defects tend to appear together but do not
share the same cause, they are called associations.

Causes and symptoms
The specific cause of many congenital abnormalities is unknown, but several factors associated with
pregnancy and delivery can increase the risk of birth
defects.

OTHER

Avian Influenza. World Health Organization. Continuously
updated [cited March 31, 2005]. <http://www.who.int/
csr/disease/avian_influenza/en/>.
Avian Flu Index. Centers for Disease Control and
Prevention. Continuously updated [cited April 1, 2005].
<http://www.cdc.gov/flu/avian/index.htm>.
Chazan, David. ‘‘Korean dish ‘may cure bird flu.’’’BBC
News. March 14, 2005 [cited March 30, 2005]. <http://
news.bbc.co.uk/go/pr/fr/-/2/hi/asia-pacific/
4347443.stm>.
Focus on the Flu. National Institute of Allergy and
Infectious Diseases. Continuously updated [cited
March 31, 2005]. <http://www2.niaid.nih.gov/
Newsroom/FocusOn/Flu04/>.

Liz Swain

Birth control see Diaphragm (birth control);
Condom; Contraception
Birth control pills see Oral contraceptives
546

Teratogens
Any substance that can cause abnormal development of the egg in the mother’s womb is called a
teratogen. In the first two months after conception,
the developing organism is called an embryo; developmental stages from two months to birth are called
fetal. Growth is rapid, and each body organ has a
critical period in which it is especially sensitive to outside influences. About 7% of all congenital defects are
caused by exposure to teratogens.
DRUGS. Only a few drugs are known to cause birth
defects, but all have the potential to cause harm.
For example, in 2003, a study found that use of topical
(local) corticosteroids in the first trimester of pregnancy
may be associated with cleft lip. Thalidomide is known
to cause defects of the arms and legs; several other
types also cause problems.


Alcohol. Drinking large amounts of alcohol while
pregnant causes a cluster of defects called fetal alcohol syndrome, which includes mental retardation,
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Birth defects

Birth trauma and uterine factors–1%
Maternal metabolic factors–1%
Maternal infection–2%
Drugs, chemicals, radiation–2%
Cytogenetic diseases–4%
Hereditary diseases–20%

Unknown causes–70%

The specific cause of many birth defects is unknown, but several factors associated with pregnancy and delivery can increase
the risk of birth defects. These factors include exposure to teratogens, drugs and other chemicals, exposure to radiation, and
infections present in the womb. (Illustration by Electronic Illustrators Group.)

heart problems, and growth deficiency. In 2004,
experts warned that binge drinking early in pregnancy
was dangerous even if the woman quit drinking later.








Antibiotics. Certain antibiotics are known tetratogens. Tetracycline affects bone growth and discolors
the teeth. Drugs used to treat tuberculosis can lead to
hearing problems and damage to a nerve in the head
(cranial damage).

Antineoplastic agents. Drugs given to treat cancer
can cause major congenital malformations, especially central nervous system defects. They also may
be harmful to the health care worker who is giving
them while pregnant.



Anticonvulsants. Drugs given to prevent seizures can
cause serious problems in the developing fetus,
including mental retardation and slow growth.
Studies in the United Kingdom and Australia have
tracked the percentage of birth defects caused by
certain antiepileptic drugs.

Hormones. Male hormones may cause masculinization of a female fetus. A synthetic estrogen (DES)
given in the 1940s and 1950s caused an increased risk
of cancer in the adult female children of the mothers
who received the drug.



Recreational drugs. Drugs such as LSD have been
associated with arm and leg abnormalities and central nervous system problems in infants. Crack
cocaine also has been associated with birth defects.
Since drug abusers tend to use many drugs and have
poor nutrition and prenatal care, it is hard to determine the effects of individual drugs.

Antipsychotic and antianxiety agents. Several drugs
given for anxiety and mental illness are known to
cause specific defects.

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547

Birth defects

KEY TERMS
Chromosome—One of the bodies in the cell
nucleus that carries genes. There are normally 46
chromosomes in humans.
Cleft lip and palate—An opening in the lip, the roof
of the mouth (hard palate), or the soft tissue in the
back of the mouth (soft palate).
Embryo—The developing baby from conception to
the end of the second month.
Gene—The The functional unit of heredity that
directs all growth and development of an organism.
Each human being has more than 100,000 genes
that determine hair color, body build, and all other
traits.
Fetus—In humans, the developing organism from
the end of the eighth week to the moment of birth.
Congenital absence of three fingers. Deformities such as this
are usually caused by damage to the developing fetus in utero.
(Photograph by Dr. P. Marazzi, Photo Researchers, Inc.
Reproduced by permission.)

CHEMICALS. Environmental chemicals such as
fungicides, food additives, and pollutants are suspected of causing birth defects, though this is difficult
to prove.
RADIATION. Exposure of the mother to high levels

of radiation can cause small skull size (microcephaly),
blindness, spina bifida, and cleft palate. How severe the
defect is depends on the duration and timing of the
exposure.
INFECTIONS. Three viruses are known to harm a

developing baby: rubella, cytomegalovirus (CMV),
and herpes simplex. Toxoplasma gondii, a parasite
that can be contracted from undercooked meat, from
dirt, or from handling the feces of infected cats, causes
serious problems. Untreated syphilis in the mother
also is harmful.
Genetic factors
A gene is a tiny, invisible unit containing information (DNA) that guides how the body forms and functions. Each individual inherits tens of thousands of
genes from each parent, arranged on 46 chromosomes.
Genes control all aspects of the body, how it works,
and all its unique characteristics, including eye color
and body size. Genes are influenced by chemicals and
radiation, but sometimes changes in the genes are
unexplained accidents. Each child gets half of its
548

Neural tube defects—A group of birth defects that
affect the backbone and sometimes the spinal chord.
Rubella—A mild, highly contagious childhood
illness caused by a virus; it is also called German
measles. It causes severe birth defects if a pregnant
woman is not immune and gets the illness in the
first three months of pregnancy.
Spina bifida—One of the more common birth
defects in which the backbone never closes.
Trait—A distinguishing feature of an individual.
Virus—A very small organism that causes infection
and needs a living cell to reproduce.

genes from each parent. In each pair of genes one
will take precedence (dominant) over the other (recessive) in determining each trait, or characteristic. Birth
defects caused by dominant inheritance include a form
of dwarfism called achondroplasia; high cholesterol;
Huntington’s disease, a progressive nervous system
disorder; Marfan syndrome, which affects connective
tissue; some forms of glaucoma, and polydactyly (extra
fingers or toes).
If both parents carry the same recessive gene,
they have a one-in-four chance that the child will
inherit the disease. Recessive diseases are severe and
may lead to an early death. They include sickle cell
anemia, a blood disorder that affects blacks, and
Tay-Sachs disease, which causes mental retardation
in people of eastern European Jewish heritage. Two
recessive disorders that affect mostly whites are:
cystic fibrosis, a lung and digestive disorder, and
phenylketonuria (PKU), a metabolic disorder. If only
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Some disorders are linked to the sex-determining
chromosomes passed along by parents. Hemophilia, a
condition that prevents blood from clotting, and
Duchenne muscular dystrophy, which causes muscle
weakness, are carried on the X chromosome. Genetic
defects also can take place when the egg or sperm are
forming if the mother or father passes along some
faulty gene material. This is more common in older
mothers. The most common defect of this kind is
Down syndrome, a pattern of mental retardation and
physical abnormalities, often including heart defects,
caused by inheriting three copies of a chromosome
rather than the normal pair.

(protrusion of part of the intestine through the abdominal wall) than women of average weight. Women who
were overweight or classified as obese also were twice as
likely to have an infant with a heart defect or multiple
birth defects than women classified as average weight.

Diagnosis
If there is a family history of birth defects or if the
mother is over 35 years old, then screening tests can be
done during pregnancy to gain information about
the health of the baby.


Alpha-fetoprotein test. This is a simple blood test
that measures the level of a substance called alphafetoprotein that is associated with some major birth
defects. An abnormally high or low level may indicate the need for further testing.



Ultrasound. The use of sound waves to examine the
shape, function, and age of the fetus is a common
procedure. It also can detect many malformations,
such as spina bifida, limb defects, and heart and
kidney problems. In 2003, researchers in England
announced a new combination of blood tests and ultrasound to detect Down syndrome sooner and more
accurately than with the usual blood screenings done
at 20 weeks of pregnancy.



Amniocentesis. This test usually is done between the
13th and 15th weeks of pregnancy. A small sample of
amniotic fluid is withdrawn through a thin needle
inserted into the mother’s abdomen. Chromosomal
analysis can rule out Down syndrome and other
genetic conditions.



Chorionic villus sampling (CVS). This test can be
done as early as the ninth week of pregnancy to
identify chromosome disorders and some genetic
conditions. A thin needle is inserted through the
abdomen or a slim tube is inserted through the
vagina that takes a tiny tissue sample for testing.

A less understood cause of birth defects results
from the interaction of genes from one or both parents
plus environmental influences. These defects are
thought to include:


Cleft lip and palate, which are malformations of the
mouth.



Clubfoot, ankle or foot deformities.



Spina bifida, an open spine caused when the tube
that forms the brain and spinal chord does not
close properly.



Water on the brain (hydrocephalus), which causes
brain damage.



Diabetes mellitus, an abnormality in sugar metabolism that appears later in life.



Heart defects.



Some forms of cancer.

A serious illness in the mother, such as an underactive thyroid, or diabetes mellitus, in which her body
cannot process sugar, also can cause birth defects in the
child. In fact, in 2003, it was shown that babies of
diabetic mothers are five times as likely to have structural heart defects as other babies. An abnormal
amount of amniotic fluid may indicate or cause birth
defects. Amniotic fluid is the liquid that surrounds and
protects the unborn child in the uterus. Too little of this
fluid can interfere with lung or limb development. Too
much amniotic fluid can accumulate if the fetus has a
disorder that interferes with swallowing. In 2003, a
study linked the mother’s weight to risk of birth defects.
Obese women were about three times more likely to
have an infant with spina bifida or omphalocele
GALE ENCYCLOPEDIA OF MEDICINE

If a birth defect is suspected after a baby is born,
then confirmation of the diagnosis is very important.
The patient’s medical records and medical history may
hold essential information. A careful physical examination and laboratory tests should be done. Special
diagnostic tests also can provide genetic information in some cases. In 2003, the March of Dimes, a
nonprofit organization, recommended that every baby
born in the United States receive, at minimum, screening for the same core group of birth defects including
phenylketonuria, congenital adrenal hyperplasia, congenital hypothryroidism, biotinidase deficiency, and
others. They were concerned that newborn screening
varied too much from state to state.
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Birth defects

one parent passes along the genes for the disorder, the
normal gene received from the other parent will
prevent the disease, but the child will be a carrier.
Having the gene is not harmful to the carrier, but
there is the 25% chance of the genetic disease showing
up in the child of two carriers.

Birthmarks

Treatment
Treatment depends on the type of birth defect and
how serious it is. When an abnormality has been
identified before birth, delivery can be planned at a
health care facility that is prepared to offer any special
care needed. Some abnormalities can be corrected
with surgery. Experimental procedures have been
used successfully in correcting some defects, like
excessive fluid in the brain (hydrocephalus), even
before the baby is born. Early reports have shown
success with fetal surgery on spina bifida patients.
By operating on these fetuses while still in the womb,
surgeons have prevented the need for shunts and
improved outcomes at birth for many newborns.
However, long-term studies still are needed. Patients
with complicated conditions usually need the help of
experienced medical and educational specialists with
an understanding of the disorder.

‘‘March of Dimes Pushes Newborn Screening.’’ Diagnostics &
Imaging Week (July 31, 2003): 10–11.
‘‘Studies Reveal Risk of Birth Defects from AEDs.’’ Pharma
Marketletter (September 13, 2004).
‘‘Topical Corticosteroids Use During Pregnancy May
Associate With Cleft Lip.’’ Biotech Week (September
24, 2003): 190.
ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914) 4287100. resourcecenter@modimes.org. <http://
www.modimes.org>.
OTHER

March of Dimes. Public Health Education Information Sheets.

Karen Ericson, RN
Teresa G. Odle

Prognosis
The prognosis for a disorder varies with the specific condition.

Prevention
Pregnant women should eat a nutritious diet.
Taking folic acid supplements before and during pregnancy reduces the risk of having a baby with serious
problems of the brain or spinal chord (neural tube
defects). It is important to avoid any teratogen that
can harm the developing baby, including alcohol and
drugs. When there is a family history of congenital
defects in either parent, genetic counseling and testing
can help parents plan for future children. Often, counselors can determine the risk of a genetic condition
occurring and the availability of tests for it. Talking to
a genetic counselor after a child is born with a defect
can provide parents with information about medical
management and available community resources.
Resources
PERIODICALS

‘‘Babies of Diabetic Mothers Have Fivefold Increase in
Structural Heart Defects.’’ Diabetes Week (October 6,
2003): 8.
Bauer, Jeff. ‘‘Researchers Link Momós Weight to Babyós
Risk of Birth Defects.’’ RN (August 2003): 97–102.
‘‘Fetal Alcohol Syndrome Is Still a Threat, Says
Publication.’’ Science Letter (September 28, 2004): 448.
‘‘Fetal Diagnostic Test Combo Shows Promise.’’ Health &
Medicine Week (October 27, 2003): 224.
‘‘Fetal Surgery for Spina Bifida Shows Benefits in Leg
Function, Fewer Shunts.’’ Health & Medicine Week
(October 20, 2003): 608.
550

I Birthmarks
Definition
Birthmarks, including angiomas and vascular
malformations, are benign (noncancerous) skin
growths composed of rapidly growing or poorly
formed blood vessels or lymph vessels. Found at
birth (congenital) or developing later in life (acquired)
anywhere on the body, they range from faint spots to
dark swellings covering wide areas.

Description
Skin angiomas, also called vascular (pertaining to
vessel) nevi (marks), are composed of blood vessels
(hemangiomas) or lymph vessels (lymphangiomas),
that lie beneath the skin’s surface. Hemangiomas,
composed of clusters of cells that line the capillaries,
the body’s smallest blood vessels, are found on the face
and neck (60%), trunk (25%), or the arms and legs
(15%). Congenital hemangiomas, 90% of which
appear at birth or within the first month of life, grow
quickly, and disappear over time. They are found in 110% of full-term infants, and 25% of premature
infants. About 65% are capillary hemangiomas
(strawberry marks), 15% are cavernous (deep) hemangiomas, and the rest are mixtures. Hemangiomas are
three times more common in girls. Usually, only one
hemangioma is found, in 20% two are found, while
fewer than 5% have three or more. Lymphangiomas
are skin bumps caused by enlarged lymph vessels anywhere on the body.
GALE ENCYCLOPEDIA OF MEDICINE

Angioma—A benign skin tumor composed of
rapidly growing, small blood or lymph vessels.
Capillaries—The smallest blood vessels, they connect the arteries and veins.
Corticosteroids—Drugs that fight inflammation.
Hemangioma—A benign skin tumor composed of
abnormal blood vessels.
Lymph vessels—Part of the lymphatic system, these
vessels connect lymph capillaries with the lymph
nodes; they carry lymph, a thin, watery fluid resembling blood plasma and containing white blood
cells.

A fading capillary hemangioma on the nose of a child.
(Photograph by Dr. P. Marazzi, Custom Medical Stock Photo.
Reproduced by permission.)

Lymphangioma—A benign skin tumor composed
of abnormal lymph vessels.
Nevus—A mark on the skin.

Vascular malformations are poorly formed blood
or lymph vessels that appear at birth or later in life.
One type, the salmon patch (nevus simplex), a pink
mark composed of dilated capillaries, is found on the
back of the neck (also called a stork bite) in 40% of
newborns, and on the forehead and eyelids (also called
an angel’s kiss) in 20%. Stork bites are found in 70%
of white and 60% of black newborns.
Found in fewer than 1% of newborns, port-wine
stains (nevus flammeus), are vascular malformations
composed of dilated capillaries in the upper and lower
layers of the skin of the face, neck, arms, and legs.
Often permanent, these flat pink to red marks develop
into dark purple bumpy areas in later life; 85% appear
on only one side of the body.
Acquired hemangiomas include spider angiomas
(nevus araneus), commonly known as spider veins,
and cherry angiomas (senile angiomas or Campbell
de Morgan spots). Found around the eyes, cheekbones, arms, and legs, spider angiomas are red marks
formed from dilated blood vessels. They occur during
pregnancy in 70% of white women and 10% of black
women, in alcoholics and liver disease patients, and in
50% of children. Cherry angiomas, dilated capillaries
found mainly on the trunk, appear in the 30s, and
multiply with aging.

Causes and symptoms
There are no known causes for congenital skin
angiomas; they may be related to an inherited weakness of vessel walls. Exposure to estrogen causes spider
angiomas in pregnant women or those taking oral
contraceptives. Spider angiomas tend to run in
families, and may be associated with liver disease,
sun exposure, and trauma.
GALE ENCYCLOPEDIA OF MEDICINE

Ulcer—A red, shallow sore on the skin.
Vascular malformation—A poorly formed blood or
lymph vessels.

Hemangiomas
Hemangiomas first appear as single or multiple,
white or pale pink marks, ranging from 2-20 cm (average 2-5 cm) in size. Some are symptomless while others
cause pain or bleeding, or interfere with normal functioning when they are numerous, enlarged, infected, or
ulcerated. Vision is affected by large marks on the
eyelids. Spider and cherry angiomas are unsightly
but symptomless.
Each type of hemangioma has a characteristic
appearance:


Capillary hemangiomas (strawberry marks). These
round, raised marks are bright red and bumpy like
a strawberry, and become white or gray when fading.



Cavernous hemangiomas. These slightly raised,
dome-shaped, blue or purple swellings are sometimes
associated with lymphangiomas or involve the soft
tissues, bone, or digestive tract.



Spider angiomas. These are symptomless, reddish
blue marks formed from blood-filled capillaries
radiating around a central arteriole (small artery) in
the shape of a spider web.



Cherry angiomas. These harmless, dilated capillaries
appear as tiny, bright red-to-violet colored bumps.



Lymphangiomas. These dilated lymph vessels form
light pink or yellow cysts (fluid- filled sacs) or swellings.
551

Birthmarks

KEY TERMS

Birthmarks

Vascular malformations
These are faint, flat, pink stains that grow as the
child grows into larger dark red or purple marks. Some
are symptomless but others bleed if enlarged or injured.
Disfiguring port-wine stains can cause emotional and
social problems. About 5% of port-wine stains on
the forehead and eyelids increase eye pressure due to
involvement of the eye and surrounding nerves.
Abnormalities of the spinal cord, soft tissues, or bone
may be associated with severe port-wine stains.
Each type has a characteristic appearance:


Salmon patches. These symptomless, light red-topink marks usually fade with time.



Port-wine stains. These flat, pink marks progress to
raised, dark red-to-purple grape-like lumps distorting the facial features, arms, or legs.

Diagnosis
Patients are treated by pediatricians (doctors who
specialize in the care of children), dermatologists (skin
disease specialists), plastic surgeons (doctors who specialize in correcting abnormalities of the appearance),
and ophthalmologists (eye disease specialists).
Angiomas and vascular malformations are not difficult to diagnose. The doctor takes a complete medical
history and performs a physical examination including
inspection and palpation of the marks. The skin is
examined for discoloration, scarring, bleeding, infection, or ulceration. The type, location, size, number,
and severity of the marks are recorded. The doctor may
empty the mark of blood by gentle pressure. Biopsies or
specialized x rays or scans of the abnormal vessels and
their surrounding areas may be performed. Patients
with port-wine stains near the eye may require skull x
rays, computed tomography scans, and vision and
central nervous system tests. Most insurance plans
pay for diagnosis and treatment of these conditions.

Treatment
Treatment choices for skin angiomas and vascular
malformations depend on their type, location, and
severity, and whether they cause symptoms, pain, or
disfigurement.
Watchful waiting
No treatment is given, but the mark is regularly
examined. This continues until the mark disappears,
or requires treatment. This approach is particularly
appropriate for the treatment of hemangiomas,
552

which often do not require treatment, since they eventually shrink by themselves.
Drugs
CORTICOSTEROIDS. Daily doses of the antiinflammatory drugs prednisone or prednisolone are
given for up to 2 months with gradual reduction of
the dose. The marks begin to subside within 7-10 days,
but may take up to 2 months to fully disappear. If no
response is seen in 2 weeks, the drug is discontinued.
Treatment may be repeated. Side effects include growth
retardation, increased blood pressure and blood sugar,
cataracts, glandular disorders, and infection. The corticosteroids triamcinolone acetate and betamethasone
sodium phosphate or acetate are injected directly into
the marks with a response usually achieved within a
week; additional injections are given in 4-6 weeks. Side
effects include tissue damage at the injection site.
INTERFERON ALPHA-2A. This drug reduces cell
growth, and is used for vascular marks that affect
vision, and that are unresponsive to corticosteroids.
Given in daily injections under the skin, a response
rate of 50% is achieved after about 7 months. Side
effects include fever, chills, muscle and joint pain,
vision disorders, low white and red blood cell counts,
fatigue, elevated liver enzymes, nausea, blood clotting
problems, and nerve damage.
ANTIBIOTICS. Oral or topical (applied to the skin)
antibiotics are prescribed for infected marks.

Surgery
LASER SURGERY. Lasers create intense heat that
destroys abnormal blood vessels beneath the skin,
without damaging normal skin. Two types of lasers
are used: the flashlamp-pulsed dye laser (FPDL) and
the neodymium:YAG (Nd:YAG) laser. The FPDL,
used mainly for strawberry marks and port-wine
stains, penetrates to a depth of 1.8 mm and causes
little scarring, while the Nd:YAG laser penetrates to
a depth of 6 mm, and is used to treat deep hemangiomas. Laser surgery is not usually painful, but can be
uncomfortable. Anesthetic cream is used for FPDL
treatment. Treatment with the Nd:YAG laser requires
local or general anesthesia. Children are usually
sedated or anesthetized. Healing occurs within 2
weeks. Side effects include bruising, skin discoloration, swelling, crusting, and minor bleeding.
SURGICAL EXCISION. Under local or general
anesthesia, the skin is cut with a surgical instrument,
and vascular marks or their scars are removed. The cut
is repaired with stitches or skin clips.

GALE ENCYCLOPEDIA OF MEDICINE

ELECTRODESICCATION. Affected
vessels
are
destroyed with the current from an electric needle.

Other treatments



Spider angiomas. These fade following childbirth and
in children, but may recur. About 90% respond to
sclerotherapy, electrodesiccation, or laser therapy.



Cherry angiomas. These are easily removed by
electrodesiccation.



Lymphangiomas. These require surgery.



Salmon patches. Eyelid marks disappear by 6-12
months of age, and forehead marks fade by age 6;
however, 50% of stork bites on the neck persist into
adulthood.



Port-wine stains. Some flat birthmarks are easily
covered with make-up. Treatment during infancy
or childhood improves results. About 95% of the
stains respond to FPDL surgery with minimal scarring;
25% will completely and 70% will partially disappear.
For unknown reasons, 5% show no improvement.

These include:




Sclerotherapy. Injection of a special solution causes
blood clotting and shrinkage with little scarring. Side
effects include stinging, swelling, bruising, scarring,
muscle cramping, and allergic reactions. This treatment is used most commonly for spider angiomas.
Embolization. Material injected into the vessel
blocks blood flow which helps control blood loss
during or reduces the size of inoperable growths. A
serious side effect, stroke, can occur if a major blood
vessel becomes blocked.



Make-up. Special brands are designed to cover birthmarks (Covermark or Dermablend).



Cleaning and compression. Bleeding marks are
cleaned with soap and water or hydrogen peroxide,
and compressed with a sterile bandage for 5-10 minutes.

Alternative treatment
Alternative treatments for strengthening weak
blood vessels include eating high-fiber foods and
those containing bioflavonoids, including citrus fruit,
blueberries, and cherries, supplementing the diet with
vitamin C, and taking the herbs, ginkgo (Ginkgo
biloba) and bilberry (Vaccinium myrtillus.)

Prognosis
The various types of birthmarks have different
prognoses:




Capillary hemangiomas. Fewer than 10% require
treatment. Without treatment, 50% disappear by
age 5, 70% by age 7, and 90% by age 9. No skin
changes are found in half while others have some
discoloration, scarring, or wrinkling. From 30-90%
respond to oral corticosteroids, and 45% respond to
injected corticosteroids; 50% respond to interferon
Alpha-2a. About 60% improve after laser surgery.
Cavernous hemangiomas. Some do not disappear
and some are complicated by ulceration or infection.
About 75% respond to Nd:YAG laser surgery but
have scarring. Severe marks respond to oral corticosteroids, but some require excision.

GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Congenital hemangiomas or vascular malformations cannot be prevented, but spider angiomas
may be prevented by exercise, weight control, and a
high-fiber diet, as well as avoidance of sun exposure,
alcohol drinking, or wearing tight hosiery.
Resources
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
American Academy of Pediatrics. 141 Northwest Point
Boulevard, Elk Grove Village, IL 60007-1098. (847)
434-4000. <http://www.aap.org>.
Congenital Nevus Support Group. 1400 South Joyce St.,
Number C-1201, Arlington, VA 22202. (703) 920-3249.
National Congenital Port Wine Stain Foundation. 123 East
63rd St., New York, NY 10021. (516) 867-5137.

Mercedes McLaughlin

Bismuth subsalicylate see Antidiarrheal
drugs

I Bites and stings
Definition
Humans can be injured by the bites or stings of
many kinds of animals, including mammals such as
dogs, cats, and fellow humans; arthropods such as
553

Bites and stings

CRYOSURGERY. Vascular marks are frozen with an
extremely cold substance sprayed onto the skin.
Wounds heal with minimal scarring.

Bites and stings

spiders, bees, and wasps; snakes; and marine animals
such as jellyfish and stingrays.

Description
Mammals
DOGS. In the United States, where the dog population exceeds 50 million, dogs surpass all other mammals
in the number of bites inflicted on humans. However,
most dog-bite injuries are minor. A telephone survey of
U.S. households conducted in 1994 led researchers to
estimate that 3,737,000 dog bites not requiring medical
attention occurred in the United States that year, versus
757,000 that required medical treatment. Studies also
show that most dog bites are from pets or other dogs
known to the bitten person, that males are more likely
than females to be bitten, and that children face a greater
risk than adults. Each year, about 10-20 Americans,
mostly children under 10 years of age, are killed by dogs.

Dog bites result in an estimated 340,000 emergency
room visits annually throughout the United States.
More than half of the bites seen by emergency departments occur at home. Children under 10 years old,
especially boys between 5 and 9 years of age, are more
likely than older people to visit an emergency room for
bite treatment. Children under 10 years old were also
much more liable to be bitten on the face, neck, and
head. Nearly all of the injuries suffered by people seeking treatment in emergency rooms were of ‘‘low severity,’’ and most were treated and released without being
admitted to the hospital or sent to another facility.
Many of the bites resulted from people attempting to
break up fights between animals.
CATS. Although cats are found in nearly a third of
U.S. households, cat bites are far less common than
dog bites. According to one study, cats inflict perhaps
400,000 harmful bites in the United States each year.
The tissue damage caused by cat bites is usually limited, but they carry a high risk of infection. Whereas
the infection rate for dog bite injuries is 15-20%, the
infection rate for cat bites is 30-40%.
HUMANS. Bites from mammals other than dogs

and cats are uncommon, with one exception—human
bites. There are approximately 70,000 human bites
each year in the United States. Because the human
mouth contains a multitude of potentially harmful
microorganisms, human bites are more infectious
than those of most other animals.
Arthropods
Arthropods are invertebrates belonging to the phylum Arthropoda, which includes insects, arachnids,
554

An insect bite caused this person’s lower lip to swell. (Custom
Medical Stock Photo. Reproduced by permission.)

A close-up view of lacerations on the shin of an adult woman
inflicted by a Rottweiler dog. (Custom Medical Stock Photo.
Reproduced by permission.)

crustaceans, and other subgroups. There are more than
700,000 species in all. The list of arthropods that bite or
sting humans is extensive and includes lice, bedbugs, fleas,
mosquitoes, black flies, ants, chiggers, ticks, centipedes,
scorpions, and other species. Spiders, bees, and wasps are
the three kinds of arthropod that most often bite people.
SPIDERS. In the United States, only two kinds of
venomous spider are truly dangerous: widow spiders
and brown (violin or fiddle) spiders. The black widow,
which is found in every state but Alaska, is probably
the most notorious widow spider. It prefers dark, dry
places such as barns, garages, and outhouses, and also
lives under rocks and logs. Disturbing a female black
widow or its web may provoke a bite. Brown spiders
also prefer sheltered places, including clothing, and
may bite if disturbed.
BEES AND WASPS. Bees and wasps will sting
to defend their nests or if they are disturbed. Species

GALE ENCYCLOPEDIA OF MEDICINE

Bites and stings

Pit

Triangular head

Profile and top views of typically nonpoisonous and poisonous snakes. Characteristic triangular head and pits on the side of the
head are indicative of poisonous pit vipers found in the United States. (Illustration by Argosy Inc.)

common to the United States include honeybees, bumblebees, yellow jackets, bald-faced hornets, brown hornets, and paper wasps. Of note are also Africanized bee
species, also called ‘‘killer bees’’ that have been found in
the United States since 1990. More than 50 Americans
die each year after being stung by a bee, wasp, or ant.
Almost all of those deaths are the result of allergic
reactions, and not of exposure to the venom itself.
Snakes
There are 20 species of venomous snakes in the
United States. These snakes are found in every state
except Maine, Alaska, and Hawaii. Each year about
8,000 Americans receive a venomous snakebite, but no
more than about 15 die, mostly from rattlesnake bites.
The venomous snakes of the United States are
divided into two families, the Crotalidae (pit vipers)
and the Elapidae. Pit vipers, named after the small
heat-sensing pit that lies between each eye and nostril,
are responsible for about 99% of the venomous snakebites suffered by Americans. Rattlesnakes, copperheads,
and cottonmouths (also called water moccasins) are pit
vipers. This family of snakes delivers its venom through
two long, hinged fangs in the upper jaw. Some pit vipers
carry a potent venom that can threaten the brain and
spinal cord. The venom of others, such as the copperheads, is less harmful.
The Elapidae family includes two kinds of venomous coral snakes indigenous to the southern and
western states. Because coral snakes are bashful creatures that come out only at night, they almost never
GALE ENCYCLOPEDIA OF MEDICINE

bite humans, and are responsible for approximately 25
bites a year in the United States. Coral snakes also
have short fangs and a small mouth, which lowers the
risk of a bite actually forcing venom into a person’s
body. However, their venom is quite poisonous.
Marine animals
Several varieties of marine animal may bite or sting.
Jellyfish and stingrays are two kinds that pose a threat
to people who live or vacation in coastal communities.

Causes and symptoms
Mammals
DOGS. A typical dog bite results in a laceration,
tear, puncture, or crush injury. Bites from large,
powerful dogs may even cause fractures and dangerous internal injuries. Also, dogs trained to attack may
bite repeatedly during a single episode. Infected bites
usually cause pain, cellulitis (inflammation of the connective tissues), and a pus-filled discharge at the
wound site within 8-24 hours. Most infections are
confined to the wound site, but many of the microorganisms in the mouths of dogs can cause systemic
and possibly life-threatening infections. Examples are
bacteremia and meningitis, especially severe in people
diagnosed with acquired immunodeficiency syndrome
(AIDS) or other health condition that increases their
susceptibility to infection. Rabies is rare among pet
dogs in the United States, most of which have been
vaccinated against the disease. Tetanus is also rare but

555

Bites and stings

Brown
recluse
spider

Black
widow
spider
(underside)

Louse

Hornet

Yellow jacket

Paper wasp

Fire ant

Honey bee

Types of spiders and insects that bite and sting. (Illustration by Argosy Inc.)

CATS. The mouths of cats and dogs contain many
of the same microorganisms. Cat scratches and bites are
also capable of transmitting the Bartonella henselae
bacterium, which can lead to cat-scratch disease, an
unpleasant but usually not life-threatening illness.

which are vulnerable to infection because of their
comparatively poor blood supply. This is why cat
bites are much more likely to become infected than
dog bites. Also, people are less inclined to view cat
bites as dangerous and requiring immediate attention;
the risk that infection has set in by the time a medical
professional is consulted is thus greater.

Cat bites are mostly found on the arms and hands.
Sharp cat teeth typically leave behind a deep puncture
wound that can reach muscles, tendons, and bones,

HUMANS. Humans bites result from fights, sexual
activity, medical and dental treatment, and seizures.
Bites also raise the possibility of spousal or child abuse.

can be transmitted by a dog bite if the victim is not
immunized.

556

GALE ENCYCLOPEDIA OF MEDICINE

Anaphylaxis—A life-threatening allergic reaction
occurring in persons hypersensitive to bites and
stings.
Antibiotics—Substances used against bacteria that
cause infection.
Antibodies—Substances created by the body to
combat infection.
Antihistamines—Drugs used to treat allergic reactions by acting against a substance called histamine.
Arachnid—Large class of arthropods that includes
spiders, scorpions, mites, and ticks. Arachnids have
a segmented body divided into two parts, one of
which has four pairs of legs but no antennae.
Arachnidism—Poisoning resulting from the bite or
sting of an arachnid.
Bacteremia—Bacteria in the blood.
Blood serum—A component of blood.
Immune system—The body system that fights
infection and protects the body against foreign
invaders and disease.
Killer bees—Hybrids of African bees accidentally
introduced into the wild in South and North
America in 1956 and first reported in Texas in
1990. They were first imported by Brazilian scientists attempting to create a new hybrid bee to
improve honey production.

SPIDERS. As a rule, people rarely see a black
widow bite, nor do they feel the bite as it occurs. The
first (and possibly only) evidence that a person has
been bitten may be a mild swelling of the injured area
and two red puncture marks. Within a short time,
however, some victims begin to experience severe muscle cramps and rigidity of the abdominal muscles.
Other possible symptoms include excessive sweating,
nausea, vomiting, headaches, and vertigo as well as
breathing, vision, and speech problems.

A brown spider’s bite can lead to necrotic arachnidism, in which the tissue in an area of up to several
inches around the bite becomes necrotic (dies), producing an open sore that can take months or years to
disappear. In most cases, however, the bite simply
produces a hard, painful, itchy, and discolored area
that heals without treatment in 2-3 days. The bite may
also be accompanied by a fever, chills, edema (an
accumulation of excess tissue fluid), nausea and vomiting, dizziness, muscle and joint pain, and a rash.
BEES AND WASPS. The familiar symptoms of bee
and wasp stings include pain, redness, swelling, and
itchiness in the area of the sting. Multiple stings can
have much more severe consequences, such as anaphylaxis, a life-threatening allergic reaction that occurs in
hypersensitive persons.

Snakes

Lymph nodes—Small, kidney-shaped organs that
filter a fluid called lymph and that are part of the
body’s immune system.
Pus—A thick yellowish or greenish fluid composed
of the remains of dead white blood cells, pathogens
and decomposed cellular debris.

Venomous pit viper bites usually begin to swell
within 10 minutes and sometimes are painful. Other
symptoms include skin blisters and discoloration,
weakness, sweating, nausea, faintness, dizziness,
bruising, and tender lymph nodes. Severe poisoning
can also lead to tingling in the scalp, fingers, and
toes, muscle contractions, an elevated heart rate,
rapid breathing, large drops in body temperature and
blood pressure, vomiting of blood, and coma.

Children often bite other children, but those bites are
hardly ever severe. Human bites are capable of transmitting a wide range of dangerous diseases, including
hepatitis B, syphilis, and tuberculosis.

Many pit viper and coral snake bites (20-60%) fail
to poison (envenomate) their victim, or introduce only a
small amount of venom into the victim’s body. The
wounds, however, can still become infected by the harmful microorganisms that snakes carry in their mouths.

Human bites fall into two categories: occlusional
(true) bites and clenched-fist injuries. The former present a lower risk of infection. The latter, which are very
infectious and can permanently damage the hand,
usually result from a fist hitting teeth during a fight.
People often wait before seeking treatment for a
clenched-fist injury, with the result that about half of
such injuries are infected by the time they are seen by a
medical professional.
GALE ENCYCLOPEDIA OF MEDICINE

Coral snake bites are painful but may be hard to
see. One to seven hours after the bite, a bitten person
begins to experience the effects of the venom, which
include tingling at the wound site, weakness, nausea,
vomiting, excessive salivation, and irrational behavior. Major nerves of the body can become paralyzed
for 6-14 days, causing double vision, difficulty swallowing and speaking, respiratory failure, and other
557

Bites and stings

Arthropods

KEY TERMS

Bites and stings

problems. Six to eight weeks may be needed before
normal muscular strength is regained.
Marine animals
JELLYFISH. Jellyfish venom is delivered by barbs
called nematocysts, which are located on the creature’s tentacles and penetrate the skin of people who
brush up against them. Instantly painful and itchy
red lesions usually result. The pain can continue up
to 48 hours. Severe cases may lead to skin necrosis,
muscle spasms and cramps, vomiting, nausea, diarrhea, headaches, excessive sweating, and other symptoms. In rare instances, cardiorespiratory failure may
also occur.
STINGRAYS. Tail spines are the delivery mechan-

ism for stingray venom. Deep puncture wounds result
that can cause an infection if pieces of spine become
embedded in the wound. A typical stingray injury
scenario involves a person who inadvertently steps
on a resting stingray and is lashed in the ankle by its
tail. Stingray venom produces immediate, excruciating
pain that lasts several hours. Sometimes the victim
suffers a severe reaction, including vomiting, diarrhea,
hemorrhage (bleeding), a drop in blood pressure, and
cardiac arrhythmia (disordered heart beat).

Diagnosis

HUMANS. Testing the blood of a person who has
been bitten for immunity to hepatitis B and other
diseases is always necessary after a human bite.
Ideally, the biter should be tested as well for the presence of transmissible disease. Clenched-fist injuries
often require evaluation by a hand surgeon or orthopedist. Because many people will deny having been in a
fight, medical professionals usually consider lacerations
over the fourth and fifth knuckles—the typical result of
a clenched-fist injury—to be evidence of a bite wound.
Medical professionals also look for indications of
spousal or child abuse when evaluating human bites.

Arthropods
SPIDERS. Because bites from widow spiders and
brown spiders require different treatments, capturing
and identifying the spider helps to establish diagnosis.

Snakes
Diagnosis relies on a physical examination of the
victim, information about the circumstances of the
bite, and a look at the snake itself (if it can safely be
killed and brought in for identification). Blood tests
and urinalysis supply important data on the victim’s
condition. Chest x-rays and electrocardiography (a
procedure for measuring heart activity) may also be
necessary.

Mammals
DOGS. Gathering information on the circum-

stances of a dog attack is a crucial part of treatment.
Medical professionals need to know when the attack
occurred (the chances of infection increase dramatically if the wound has been left untreated for more
than eight hours) and what led to the attack (unprovoked attacks are more likely to be associated with
rabies). A person’s general health must also be
assessed, including the tetanus immunization history
if any, as well as information concerning possible
allergies to medication and pre-existing health problems that may increase the risk of infection.
A physical examination requires careful scrutiny of
the wound, with special attention to possible bone,
joint, ligament, muscle, tendon, nerve, or blood-vessel
damage caused by deep punctures or severe crush injuries. Serious hand injuries should be evaluated by a
specialized surgeon. Most of the time, laboratory tests
for identifying the microorganisms in bite wounds are
performed if infection is present. X rays and other
diagnostic procedures may also be necessary.
CATS. The diagnostic procedures used for dog
bites also apply to cat bites.

558

Treatment
Mammals
DOGS. Minor dog bites can be treated at home. The
American Academy of Family Physicians recommends
gently washing the wound with soap and water and then
applying pressure to the injured area with a clean towel
to stop the bleeding. The next step is to apply antibiotic ointment and a sterile bandage to the wound.
To reduce swelling and fend off infection, ice should
be applied and the injured area kept elevated above
the level of the heart. The wound should be cleaned
and covered with ointment twice a day until it heals.

Any dog bite that does not stop bleeding after
15 minutes of pressure must be seen by a medical
professional. The same is true for bites that are deep
or gaping; for bites to the head, hands, or feet; and for
bites that may have broken a bone, damaged nerves,
or caused a major injury of another kind. Bite victims
must also watch for infection. A fever is one sign of
infection, as are redness, swelling, warmth, increased
tenderness, and pus at the wound site. Diabetics, people with AIDS or cancer, individuals who have not had
a tetanus shot in five years, and anyone else who has a
GALE ENCYCLOPEDIA OF MEDICINE

Medical treatment of dog bites involves washing
the wound with an anti-infective solution. Removal of
dead and damaged tissue (under local, regional, or
general anesthetic) may be required after the wound
has been washed, and any person whose tetanus shots
are not up to date should receive a booster injection.
Some wounds are left open and allowed to heal on
their own, while others require stitches (stitching may
be delayed a few days if infection is a concern). Many
emergency departments prescribe antibiotics for all
people with dog bites, but some researchers suggest
that antibiotics are usually unnecessary and should
be limited to those whose injuries or other health
problems make them likely candidates for infection.
A follow-up visit after one or two days is generally
required for anyone who has received bite treatment.
CATS. Because of the high risk of infection, people
who are bitten by a cat should always see a doctor. Cat
scratches do not require professional medical treatment unless the wound appears infected or the
scratched person has a weakened immune system.

Medical treatment for cat bites generally follows
the procedures used for dog bites. Experts advise,
however, that cat-bite wounds should always be left
open to prevent infection. Persons who have been
bitten by cats generally receive antibiotics as a preventive measure.
HUMANS. Human bites should always be examined by a doctor. Such bites are usually treated with
antibiotics and left open because of the high risk of
infection. A study released in June 2004 showed that
routine use of antibiotics for human bites may not be
necessary, as physicians try to minimize overuse of
antibiotics. Superficial wounds in low-risk areas may
no longer need antibiotic treatment, but more serious
human bites to high-risk areas such as the hands
should be treated with antibiotics to prevent serious
infection. A person who has been bitten may also
require immunization against hepatitis B and other
diseases. Persons who are being treated for a
clenched-fist injury will require a daily follow-up
examination for 3-5 days.

Arthropods
SPIDERS. No spider bite should be ignored.
The antidote for severe widow spider bites is a substance called antivenin, which contains antibodies
taken from the blood serum of horses injected with
spider venom. Doctors exercise caution in using

GALE ENCYCLOPEDIA OF MEDICINE

antivenin, however, because it can trigger anaphylactic shock, a potentially deadly (though treatable) allergic reaction, and serum sickness, an inflammatory
response that can give rise to joint pain, a fever, rashes,
and other unpleasant, though rarely serious,
consequences.
An antivenin for brown spider bites exists as well,
but it is not yet available in the United States. The drug
dapsone, used to treat leprosy, can sometimes stop the
tissue death associated with a brown spider bite.
Necrotic areas may need debridement (removal of
dead and damaged tissue) and skin grafts. Pain medications, antihistamines, antibiotics, and tetanus shots are
a few of the other treatments that are sometimes necessary after a bite from a brown spider or widow spider.
BEES AND WASPS. Most stings can be treated at
home. A stinger that is stuck in the skin can be scraped
off with a blade, fingernail, credit card, or piece of
paper (using tweezers may push more venom out of
the venom sac and into the wound). The area should
be cleaned and covered with an ice pack. Aspirin and
other pain medications, oral antihistamines, and calamine lotion are good for treating minor symptoms.
Putting meat tenderizer on the wound has no effect.

Persons who have been stung and experience an
allergic reaction, or who are at risk due to their medical
history, require immediate medical attention. The danger
signs, which usually begin 10 minutes after an individual
is stung (though possibly not for several hours), include
nausea, faintness, chest pain, abdominal cramps,
diarrhea, and difficulty swallowing or breathing.
Snakes
Although most snakes are not venomous, any snakebite should immediately be examined at a hospital.
While waiting for emergency help to arrive, the victim
should wash the wound site with soap and water, and
then keep the injured area still and at a level lower than
the heart. Ice should never be used on the wound site
nor should attempts be made to suck out the venom.
Making a cut at the wound site is also dangerous. It is
important to stay calm and wait for emergency medical
aid if it can arrive quickly. Otherwise, the victim should
proceed directly to a hospital.
When the victim arrives at a hospital, the medical
staff must determine whether the bite was inflicted by
a venomous snake and, if so, whether envenomation
occurred and how much venom the person has
received. Patients may develop low blood pressure,
abnormal blood clotting, or severe pain, all of which
require aggressive treatment. Fortunately, the effects
of some snakebites can be counteracted with
559

Bites and stings

medical problem that can increase susceptibility to
infection should seek medical treatment no matter
how minor the bite appears.

Bites and stings

antivenin. Minor rattlesnake envenomations can be
successfully treated without antivenin, as can copperhead and water-moccasin bites. However, coral snake
envenomations and the more dangerous rattlesnake
envenomations require antivenin, sometimes in large
amounts. Other treatment measures include antibiotics
to prevent infection and a tetanus booster injection.
Marine animals
JELLYFISH. Vinegar and other acidic substances
are used to neutralize jellyfish nematocysts still clinging to the skin, which are then scraped off. Anesthetic
ointments, antihistamine creams, and steroid lotions
applied to the skin are sometimes beneficial. Other
measures may be necessary to counter the many harmful effects of jellyfish stings, which, if severe, require
emergency medical care.
STINGRAYS. Stingray wounds should be washed
with saltwater and then soaked in very hot water for
30-90 minutes to neutralize the venom. Afterwards,
the wound should be examined by a doctor to ensure
that no pieces of spine remain.

Alternative treatment
Arthropods
Several alternative self-care approaches are used
to treat minor bee, wasp, and other arthropod stings,
including aromatherapy, ayurvedic medicine, flower
remedies, herbs, homeopathy, and nutritional therapy.

Prognosis
Mammals
Prompt treatment and recognizing that even
apparently minor bites can have serious consequences
are the keys to a good outcome after a mammal bite.
Infected bites can be fatal if neglected. Surgery and
hospitalization may be needed for severe bites.
Arthropods

can experience
anaphylaxis.

severe

and

occasionally

fatal

Snakes
A snakebite victim’s chances of survival are excellent if medical aid is obtained in time. Some bites,
however, result in amputation, permanent deformity,
or loss of function in the injured area.
Marine animals
STINGRAYS. Stingray venom kills its human victims on rare occasions.

Prevention
Mammals
DOGS. The risk of a dog bite injury can be reduced
by avoiding sick or stray dogs, staying away from
dogfights (people often get bitten when they try to
separate the animals), and not behaving in ways that
might provoke or upset dogs, such as wrestling with
them or bothering them while they are sleeping, eating,
or looking after their puppies. Special precautions
need to be taken around infants and young children,
who must never be left alone with a dog. Pit bulls,
rottweilers, and German shepherds (responsible for
nearly half of all fatal dog attacks in the United
States in 1997-2000) are potentially dangerous pets in
households where children live or visit. For all breeds
of dog, obedience training as well as spaying or neutering lessen the chances of aggressive behavior.
CATS. Prevention involves warning children to
stay away from strange cats and to avoid rough play
and other behavior that can anger cats and cause them
to bite.

Arthropods
SPIDERS. Common-sense precautions include
clearing webs out of garages, outhouses, and other
places favored by venomous spiders; keeping one’s
hands away from places where spiders may be lurking;
and, when camping or vacationing, checking clothing,
shoes, and sleeping areas.

SPIDERS. Even without treatment, adults usually
recover from black widow bites after 2-3 days. Those
most at risk of dying are very young children, the
elderly, and people with high blood pressure. In the
case of brown spider bites, the risk of death is greatest
for children, though rare.

BEES AND WASPS. When possible, it is advised to
avoid the nests of bees and wasps and to not eat sweet
food or wear bright clothing, perfumes, or cosmetics
that attract bees and wasps.

BEES AND WASPS. The pain and other symptoms of
a bee or wasp sting normally fade away after a few
hours. People who are allergic to such stings, however,

Emergency medical kits containing self-administrable epinephrine to counter anaphylactic shock are
available for allergic people and should be carried by

560

GALE ENCYCLOPEDIA OF MEDICINE

Snakes
Snakes should not be kept as pets. Measures such
as mowing the lawn, keeping hedges trimmed, and
removing brush from the yard also discourages snakes
from living close to human dwellings. Tongs should be
used to move brush, lumber, and firewood, to avoid
exposing one’s hands to snakes that might be lying
underneath. Similarly, golfers should never use their
hands to retrieve golf balls from a water hole, since
snakes can be hiding in the rocks and weeds. Caution
is also necessary when walking through weedy or grassy
areas, and children should be prevented from playing in
weedy, vacant lots and other places where snakes may
live. Leather boots and long pants offer hikers and
campers some protection from bites. Approaching a
snake, even a dead one, can be dangerous, for the
venom of recently killed snakes may still be active.

prevents the toxicity of widow spider venoms.’’ Annals
of Emergency Medicine 37, no. 2 (2001): 154-160.
Jarvis R. M., M. V. Neufeld, and C. T. Westfall. ‘‘Brown
recluse spider bite to the eyelid.’’ Ophthalmology 107,
no. 8 (2000): 1492-1496.
Metry, D. W., and A. A. Hebert. ‘‘Insect and arachnid
stings, bites, infestations, and repellents.’’ Pediatric
Annals 29, no. 1 (2000): 39-48.
Sams, H. H., C. A. Dunnick, M. L. Smith, and L. E. King.
‘‘Necrotic arachnidism.’’ Journal of the American
Academy of Dermatology 44, no. 4 (2001): 561-573.
Sams, HH. ‘‘Nineteen documented cases of Loxosceles
reclusa envenomation.’’ Journal of the American
Academy of Dermatology 44, no.4 (2001): 603-608.
ORGANIZATIONS

American Academy of Emergency Medicine. 611 East Wells
Street, Milwaukee, WI 53202. (800) 884-2236. Fax:
(414) 276-3349. <http://www.aaem.org/>.
American Academy of Family Physicians. 11400 Tomahawk
Creek Parkway, Leawood, KS 66211-2672. (913) 9066000. <http://www.aafp.org/>. fp@aafp.org.
American Medical Association. 515 N. State Street, Chicago,
IL 60610. (312) 464-5000. <http://www.ama-assn.org/>.
OTHER

Marine animals
JELLYFISH. Prevention of jellyfish stings includes
obeying posted warning signs at the beach. Also, jellyfish tentacles may be transparent and up to 120 ft
(36.5 m) long, therefore great caution must be exercised whenever a jellyfish is sighted nearby. An overthe-counter cream was being tested at the Stanford
University School of Medicine in the summer of
2004. In early tests, it was effective in helping to prevent some jellyfish contact.

City of Phoenix, Arizona. <http://www.ci.phoenix.az.us/
FIRE/bitessna.html>.
Southwestern University School of Medicine. <http://
www.swmed.edu/toxicology/toxlinks.html>.
Toxicology Professional Groups. <http://www.pitt.edu/
~martint/pages/motoxorg.htm#AAPCC>.
University of Sydney, Australia. <http://www.usyd.edu.au/
su/anaes/spiders.html>.
Vanderbilt University. <http://www.mc.vanderbilt.edu/
clintox/>.

L. Fleming Fallon Jr., MD, PhD
Teresa G. Odle

STINGRAYS. Shuffling while walking through shal-

low areas that may be inhabited by stingrays will disturb the water, causing the animal to move before it
can be stepped on.

Black death see Plague

Resources
BOOKS

Holve, Steve. ‘‘Envenomations.’’ In Cecil Textbook of
Medicine, edited by Lee Goldman and J. Claude
Bennett, 21st ed. Philadelphia: W. B. Saunders, 2000,
pp. 2174-2178.
Sutherland, Struan, and Tibballs, James. Australian Animal
Toxins. 2nd ed. New York, Oxford Univ Press, 2001.
PERIODICALS

‘‘Cream May Ward Off Jellyfish.’’ Drug Week (June 25,
2004): 553.
‘‘Do All Human Bite Wounds Need Antibiotics?’’
Emergency Medicine Alert (June 2004): 3.
Graudins, A., M. Padula, K. Broady, and G. M. Nicholson.
‘‘Red-back spider (Latrodectus hasselti) antivenom
GALE ENCYCLOPEDIA OF MEDICINE

I Black lung disease
Definition
Black lung disease is the common name for coal
workers’ pneumoconiosis (CWP) or anthracosis, a
lung disease of older workers in the coal industry,
caused by inhalation, over many years, of small
amounts of coal dust.

Description
The risk of having black lung disease is directly
related to the amount of dust inhaled over the
561

Black lung disease

them at all times. People who suspect they are allergic
should consult an allergist about shots that can reduce
reactions to bee and wasp venom.

Black lung disease

KEY TERMS
Emphysema—A disease in which the tiny air sacs in
the lungs become damaged, leading to shortness of
breath, and respiratory and heart failure.
Fibrosis—The growth of scar tissue, often as a
response to injury, infection, or inflammation.
Pulmonary function test—A group of procedures
used to evaluate the function of the lungs and confirm the presence of certain lung disorders.

A light micrograph of a human lung containing particles of
inspired coal dust (anthracosis). The black masses shown
are groups of coal dust particles. (Photograph by Astrid &
Hanns-Frieder Michler, Photo Researchers, Inc. Reproduced by
permission.)

years; the disease typically affects workers over age 50.
Its common name comes from the fact that the inhalation of heavy deposits of coal dust makes miners lungs
look black instead of a healthy pink. Although people
who live in cities often have some black deposits in
their lungs from polluted air, coal miners have much
more extensive deposits.
In the years since the federal government has
regulated dust levels in coal mines, the number of
cases of black lung disease has fallen sharply. Since
the Federal Coal Mine Health and Safety Act of 1969,
average dust levels have fallen from 8.0 mg. per cubic
meter to the current standard of 2.0 mg. per cubic
meter. The 1969 law also set up a black lung disability
benefits program to compensate coal miners who have
been disabled by on-the-job dust exposure.
Despite the technology available to control the
hazard, however, miners still run the risk of developing this lung disease. The risk is much lower today,
however; fewer than 10% of coal miners have any x
ray evidence of coal dust deposits. When there is such
evidence, it often shows up as only small black spots
less than 0.4 in (1 cm). in diameter, and may have been
caused by smoking rather than coal dust. This condition is called ‘‘simple CWP’’ and does not lead to
symptoms or disability.

Causes and symptoms
Since the particles of fine coal dust, which a miner
breathes when he is in the mines, cannot be destroyed
within the lungs or removed from them, builds up.
Eventually, this build-up causes thickening and
562

Silica dust—A type of dust from silica (crystalline
quartz) which causes breathing problems in workers in the fields of mining, stone cutting, quarrying
(especially granite), blasting, road and building
construction industries that manufacture abrasives,
and farming. Breathing the dust causes silicosis, a
severe disease that can scar the lungs.

scarring, making the lungs less efficient in supplying
oxygen to the blood.
The primary symptom of the disease is shortness
of breath, which gradually gets worse as the disease
progresses. In severe cases, the patient may develop
cor pulmonale, an enlargement and strain of the right
side of the heart caused by chronic lung disease. This
may eventually cause right-sided heart failure.
Some patients develop emphysema (a disease in
which the tiny air sacs in the lungs become damaged,
leading to shortness of breath, and respiratory and
heart failure) as a complication of black lung disease.
Others develop a severe type of black lung disease
called progressive massive fibrosis, in which damage
continues in the upper parts of the lungs even after
exposure to the dust has ended. Scientists aren’t sure
what causes this serious complication. Some think
that it may be due to the breathing of a mixture of
coal and silica dust that is found in certain mines.
Silica is far more likely to lead to scarring than coal
dust alone.

Diagnosis
Black lung disease can be diagnosed by checking a
patient’s history for exposure to coal dust, followed by
a chest x-ray to discover if the characteristic spots in
the lungs caused by coal dust are present. A pulmonary
function test may aid in diagnosis.
X rays can detect black lung disease before it
causes any symptoms. If exposure to the dust is
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
There is no treatment or cure for this condition,
although it is possible to treat complications such as
lung infections and cor pulmonale. Further exposure
to coal dust must be stopped.

Prognosis
Those miners with simple CWP can lead a normal
life. However, patients who develop black lung disease
at an early age, or who have progressive massive
fibrosis, have a higher risk of premature death.

Prevention
The only way to prevent black lung disease is to
avoid long-term exposure to coal dust. Coal mines
may help prevent the condition by lowering coal dust
levels and providing protective clothes to coal
miners.
A light micrograph of a human lung containing
particles of inspired coal dust (anthracosis). The black
masses shown are groups of coal dust particles.
Resources
ORGANIZATIONS

Mine Safety and Health Administration. 4015 Wilson Blvd.
Arlington, VA 22203. (703) 235-1910. <http://
www.msha.gov>.

Carol A. Turkington

Bladder calculi see Bladder stones

I Bladder cancer
Definition
Bladder cancer is a disease in which the cells lining
the urinary bladder lose the ability to regulate their
growth and start dividing uncontrollably. This abnormal growth results in a mass of cells that form a tumor.

Description
Bladder cancer is the sixth most common cancer
in the United States. The American Cancer Society
(ACS) estimated that in 2001, approximately 54,300
GALE ENCYCLOPEDIA OF MEDICINE

new cases of bladder cancer would be diagnosed
(about 39,200 men and 15,100 women), causing
approximately 12,400 deaths. The rates for men of
African descent and Hispanic men are similar and
are approximately one-half of the rate among white
non-Hispanic men. The lowest rate of bladder cancer
occurs in the Asian population. Among women, the
highest rates also occur in white non-Hispanic females
and are approximately twice the rate for Hispanics.
Women of African descent have higher rates of bladder cancer than Hispanic women.
The urinary bladder is a hollow muscular organ
that stores urine from the kidneys until it is excreted out
of the body. Two tubes called the ureters bring the urine
from the kidneys to the bladder. The urethra carries
the urine from the bladder to the outside of the body.
Bladder cancer has a very high rate of recurrence.
Even after superficial tumors are completely removed,
there is a 75% chance that new tumors will develop
in other areas of the bladder. Hence, patients need
frequent and thorough follow-up care.

Causes and symptoms
Although the exact cause of bladder cancer is not
known, smokers are twice as likely as nonsmokers to get
the disease. Hence, smoking is considered the greatest
risk factor for bladder cancer. Workers who are exposed
to certain chemicals used in the dye industry and in the
rubber, leather, textile, and paint industries are believed
to be at a higher risk for bladder cancer. The disease also
is three times more common in men than in women;
caucasians also are at an increased risk. The risk of
bladder cancer increases with age. Most cases are
found in people who are 50–70 years old. In 2003, studies
showed that hormone replacement therapy (HRT), a
treatment used by many postmenopausal women, significantly increased the risk of bladder and other cancers.
Frequent urinary infections, kidney and bladder
stones, and other conditions that cause long-term
irritation to the bladder may increase the risk of getting
bladder cancer. A past history of tumors in the bladder
also could increase one’s risk of getting other tumors.
One of the first warning signals of bladder cancer is
blood in the urine. Sometimes, there is enough blood to
change the color of the urine to a yellow-red or a dark
red. At other times, the color of the urine appears
normal but chemical testing of the urine reveals the
presence of blood cells. A change in bladder habits
such as painful urination, increased frequency of
urination and a feeling of needing to urinate but not
being able to do so are some of the signs of possible
563

Bladder cancer

stopped at that point, progression of the disease may
be prevented.

Bladder cancer

Bladder

Ureter

Epithalial Lining

Muscle

Cancer

Urethra

Bladder cancer on the inner lining of the bladder. (Illustration by Argosy Inc.)

bladder cancer. All of these symptoms also may be
caused by conditions other than cancer, but it is important to see a doctor and have the symptoms evaluated.
When detected early and treated appropriately, patients
have a very good chance of being cured completely.

Diagnosis
If a doctor has any reason to suspect bladder cancer, several tests can help find out if the disease is
present. As a first step, a complete medical history
will be taken to check for any risk factors. A thorough
physical examination will be conducted to assess all the
signs and symptoms. Laboratory testing of a urine
sample will help to rule out the presence of a bacterial
infection. In a urine cytology test, the urine is examined
under a microscope to look for any abnormal or cancerous cells. A catheter (tube) can be advanced into
the bladder through the urethra, and a salt solution is
passed through it to wash the bladder. The solution
can then be collected and examined under a microscope
to check for the presence of cancerous cells.
A test known as the intravenous pyelogram (IVP)
is an x–ray examination that is done after a dye is
injected into the blood stream through a vein in the
arm. The dye travels through the blood stream and
then reaches the kidneys to be excreted. It clearly outlines the kidneys, ureters, bladder, and urethra.
Multiple x rays are taken to detect any abnormality
in the lining of these organs.
564

The physician may use a procedure known as a
cystoscopy to view the inside of the bladder. A thin
hollow lighted tube is introduced into the bladder
through the urethra. If any suspicious looking masses
are seen, a small piece of the tissue can be removed
from it using a pair of biopsy forceps. The tissue is then
examined microscopically to verify if cancer is present,
and if so, to identify the type of cancer.
If cancer is detected and there is evidence to indicate that it has metastasized (spread) to distant sites in
the body, imaging tests such as chest x rays, computed
tomography scans (CT), and magnetic resonance imaging (MRI) may be done to determine which organs
are affected. Bladder cancer generally tends to spread
to the lungs, liver, and bone.

Treatment
Treatment for bladder cancer depends on the
stage of the tumor. The patient’s medical history,
overall health status, and personal preferences also
are taken into account when deciding on an appropriate treatment plan. The three standard modes of treatment available for bladder cancer are surgery,
radiation therapy, and chemotherapy. In addition,
newer treatment methods such as photodynamic therapy and immunotherapy also are being investigated in
clinical trials.
Surgery is considered an option only when the disease is in its early stages. If the tumor is localized to a
GALE ENCYCLOPEDIA OF MEDICINE

Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic purposes.
Chemotherapy—Treatment with anticancer drugs.
Computed tomography (CT) scan—A medical procedure where a series of x rays are taken and put
together by a computer in order to form detailed
pictures of areas inside the body.
Cystoscopy—A diagnostic procedure where a hollow lighted tube, (cystoscope) is used to look inside
the bladder and the urethra.
Electrofulguration—A procedure where a highenergy laser beam is used to burn the cancerous tissue.
Immunotherapy—Treatment of cancer by stimulating the body’s immune defense system.
Intravenous pyelogram (IVP)—A procedure where a
dye is injected into a vein in the arm. The dye travels
through the body and then concentrates in the urine
to be excreted. It outlines the kidneys, ureters, and
the urinary bladder. An x ray of the pelvic region is
then taken and any abnormalities of the urinary tract
are revealed.
Magnetic Resonance Imaging (MRI)—A medical
procedure used for diagnostic purposes where pictures of areas inside the body can be created using a
magnet linked to a computer.
Partial cystectomy—A surgical procedure where the
cancerous tissue is removed by cutting out a small
piece of the bladder.

small area and has not spread to the inner layers of the
bladder, then the surgery is done without cutting open
the abdomen. A cytoscope is introduced into the bladder through the urethra, and the tumor is removed
through it. This procedure is called a transurethral
resection (TUR). Passing a high-energy laser beam
through the cytoscope and burning the cancer may
treat any remaining cancer. This procedure is known
as electrofulguration. If the cancer has invaded the walls
of the bladder, surgery will be done through an incision
in the abdomen. Cancer that is not very large can be
removed by partial cystectomy, a procedure where a
part of the bladder is removed. If the cancer is large or
is present in more than one area of the bladder, a radical
cystectomy is done. In this operation, the entire bladder
and adjoining organs also may be removed. In men, the
prostate is removed, while in women, the uterus, ovaries, and fallopian tubes are removed.
GALE ENCYCLOPEDIA OF MEDICINE

Photodynamic therapy—A novel mode of treatment that uses a combination of special light
rays and drugs are used to destroy the cancerous
cells. First, the drugs, which make cancerous cells
more susceptible to the light rays, are introduced
into the bladder. Then the light is shone on the
bladder to kill the cells.
Radiation therapy—Treatment using high-energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Radical cystectomy—A surgical procedure that is
used when the cancer is in more than one area of
the bladder. Along with the bladder, the adjoining
organs also are removed. In men, the prostate is
removed, while in women, the ovaries, fallopian
tubes and uterus may be removed.
Stoma—An artificial opening between two cavities or between a cavity and the surface of the
body.
Transurethral resection—A surgical procedure to
remove abnormal tissue from the bladder. The technique involves the insertion of an instrument called a
cytoscope into the bladder through the urethra, and
the tumor is removed through it.
Urostomy—A surgical procedure consisting of cutting the ureters from the bladder and connecting
them to an opening (see stoma) on the abdomen,
allowing urine to flow into a collection bag.

If the entire urinary bladder is removed, an alternate place must be created for the urine to be stored
before it is excreted out of the body. To do this, a piece
of intestine is converted into a small bag and attached
to the ureters. This is then connected to an opening
(stoma) that is made in the abdominal wall. The procedure is called a urostomy. In some urostomy procedures, the urine from the intestinal sac is routed into a
bag that is placed over the stoma in the abdominal
wall. The bag is hidden by the clothing and has to be
emptied occasionally by the patient. In a different
procedure, the urine is collected in the intestinal sac,
but there is no bag on the outside of the abdomen. The
intestinal sac has to be emptied by the patient, by
placing a drainage tube through the stoma.
Radiation therapy that uses high-energy rays to
kill cancer cells is generally used after surgery to
565

Bladder cancer

KEY TERMS

Bladder cancer

destroy any remaining cancer cells that may not have
been removed during surgery. If the tumor is in a
location that makes surgery difficult, or if it is large,
radiation may be used before surgery to shrink the
tumor. In cases of advanced bladder cancer, radiation
therapy is used to ease the symptoms such as pain,
bleeding, or blockage. Radiation can be delivered by
external beam, where a source of radiation that is
outside the body focuses the radiation on the area of
the tumor. Occasionally, a small pellet of radioactive
material may be placed directly into the cancer. This is
known as interstitial radiation therapy.
Chemotherapy uses anticancer drugs to destroy
the cancer cells that may have migrated to distant
sites. The drugs are introduced into the bloodstream
by injecting them into a vein in the arm or taking
them orally in pill form. Generally a combination of
drugs is more effective than any single drug in treating
bladder cancer. Chemotherapy may be given following surgery to kill any remaining cancer cells. It also
may be given even when no remaining cancer cells
can be seen. This is called adjuvant chemotherapy.
Anticancer drugs, including thiotepa, doxorubicin,
and mitomycin, also may be instilled directly into
the bladder (intravesicular chemotherapy) to treat
superficial tumors. In 2003, the FDA was giving fast
track designation to a form of paclitaxel, a common
anticancer drug, that was shown effective in treating
metastatic or locally advanced bladder cancer.
A 2003 report stated that giving patients with bladder cancer chemotherapy followed by surgery may
improve their outcomes. In the study of 307 patients,
those with this combination of therapy lived two
years longer than those treated with surgery only.
Immunotherapy, or biological therapy, uses the
body’s own immune cells to fight the disease. To treat
superficial bladder cancer, bacille Calmette-Guerin
(BCG) may be instilled directly into the bladder. BCG
is a weakened (attenuated) strain of the tuberculosis
bacillus that stimulates the body’s immune system to
fight the cancer. This therapy has been shown to be
effective in controlling superficial bladder cancer.
Photodynamic treatment is a novel mode of treatment that uses special chemicals and light to kill the
cancerous cells. First, a drug is introduced into the
bladder that makes the cancer cells more susceptible
to light. Following that, a special light is shone on the
bladder in an attempt to destroy the cancerous cells.
New treatments are continuously being investigated. Scientists have made great strides in gene mapping and research in the twenty-first century. In 2003,
a type of gene therapy was being tested on patients
566

with bladder cancer with success, but further enhancements were needed.

Prognosis
When detected in early stages, the prognosis for
those with bladder cancer is excellent. At least 94% of
people survive five years or more after initial diagnosis. However, if the disease has spread to the nearby
tissues, the survival rate drops to 49%. If it has metastasized to distant organs such as the lung and liver,
commonly only 6% of patients will survive five years
or more. As newer treatment methods are developed,
some prognoses improve. For example, neoadjuvant
chemotherapy, or giving certain chemotherapy drugs
following surgery, may help people live up to
31 months longer than previous treatments allowed.

Prevention
Since the exact causes of bladder cancer are not
known, there is no certain way to prevent it. Avoiding
risk factors whenever possible is the best alternative.
Since smoking doubles one’s risk of getting bladder cancer, avoiding tobacco may prevent at least half
the deaths that result from bladder cancer. Taking
appropriate safety precautions when working with
organic cancer-causing chemicals is another way of
preventing the disease. Women should discuss the
risks vs. benefits of hormone replacement therapy
with their physicians.
If a person has had a history of bladder cancer, or
has been exposed to cancer-causing chemicals, he or
she is considered to be at an increased risk of getting
bladder cancer. Similarly, kidney stones, frequent urinary infections, and other conditions that cause longterm irritation to the bladder also increase the chance
of getting the disease. In such cases, it is advisable to
undergo regular screening tests such as urine cytology,
cystoscopy and x rays of the urinary tract, so that
bladder cancer can be detected at its early stages and
treated appropriately.
Resources
PERIODICALS

Good, Brian. ‘‘Battle Against Bladder Cancer.’’ Men’s
Health 18 (December 2003): 32.
Grossman, H. Barton, et al. ‘‘Neoadjuvant Chemotherapy
Plus Cystectomy Compared With Cystectomy Alone
for Locally Advanced Bladder Cancer.’’ The New
England Journal of Medicine (August 28, 2003): 859.
‘‘HRT Increases Risk of Gallbladder, Breast, Endometrial,
and Bladder Cancer.’’ Women’s Health Weekly (July 17,
2003): 31.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Bladder—A small organ that serves as the reservoir
for urine prior to its passing from the body during
urination.
Prostate gland—A small gland in the male genitals
that contributes to the production of seminal fluid.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
American Foundation for Urologic Disease. 300 W. Pratt
St., Suite 401. Baltimore, MD 21201. Phone: (800)828-7866.
Cancer Research Institute. 681 Fifth Ave., New York, N.Y.
10022. (800) 992-2623. <http://
www.cancerresearch.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
Oncolink. University of Pennsylvania Cancer Center.
<http://cancer.med.upenn.edu>.
OTHER

‘‘Bladder Cancer.’’ National Cancer Institute Page.<http://
www.nci.nih.gov>.

Lata Cherath, PhD
Teresa G. Odle

Bladder removal see Cystectomy
Bladder resection see Transurethral bladder
resection

Urinary tract—The system of organs that produces
and expels urine from the body. This system begins
at the kidneys, where the urine is formed; passes
through the bladder; and, ends at the urethra,
where urine is expelled.

Causes and symptoms
While the exact causes of the formation of bladder
stones are not completely understood, bladder stones
usually occur because of urinary tract infection (UTI),
obstruction of the urinary tract, enlargement of the
prostate gland in men, or the presence of foreign
bodies in the urinary tract. Diet and the amount of
fluid intake also appear to be important factors in the
development of bladder stones.
Ninety-five percent of all bladder stones occur
in men, most of who have an enlarged prostate gland or
a UTI. These stones are rarely seen in children or
in African Americans. People with gout may develop bladder stones composed almost entirely of uric acid.
The symptoms of bladder stones may become
evident when the wall of the bladder is scratched or
when the urinary tract becomes obstructed by the
stone. These symptoms include:

I Bladder stones



abnormally dark colored urine



blood in the urine

Definition



difficulty urinating



frequent urge to urinate



lower abdominal pain



pain or discomfort in the penis

Bladder stones are crystalline masses that form
from the minerals and proteins, which naturally
occur in urine. These types of stones are much less
common than kidney stones.

Description
Bladder stones can form anywhere in the urinary
tract before depositing in the bladder. They begin as tiny
granules about the size of a grain of sand, but they can
grow to more than an inch in diameter. These stones
can block the flow of urine causing pain and difficulty
with urination. They can also scratch the bladder
wall, which may lead to bleeding or infection.
GALE ENCYCLOPEDIA OF MEDICINE

Some people with bladder stones also may experience an inability to control urination (urinary
incontinence).

Diagnosis
The diagnosis of bladder stones is usually made
after a physical examination, which may include a
rectal examination to check for enlargement of the
prostate gland. Urine tests are then used to determine
567

Bladder stones

‘‘Intravesical Gene Therapy Appears Safe for Those
With Local Bladder Cancer.’’ Cancer Weekly (July 8,
2003): 144.
‘‘Tocosol Paclitaxel Receives Expedited Review for Bladder
Cancer Indication.’’ Biotech Week (November 26,
2003): 443.

Bladder training

if there is blood or indications of an UTI in the urine. If
bladder stones are suspected, bladder or pelvic x rays
may be ordered. Stones that are large enough to cause
problems with urinary function are almost always
detectable by x ray.

an enlarged prostate gland or UTI. The consumption
of at least six to eight eight-ounce glasses of water per
day and/or the regular consumption of cranberry juice
may help to prevent recurrences of bladder stones.
Resources

Treatment
Many bladder stones can be passed out of the
body in the urine. People with small bladder stones
will be asked to increase their fluid intakes to at least
six to eight eight-ounce glasses of water per day to
increase urinary output. If the stones do not pass
after two weeks, or if the patient’s symptoms become
worse, further medical treatment may be required.
A large bladder stone, or small stone that the patient
cannot pass in the urine, may be broken up into smaller
stones using ultrasound (shock waves). These smaller
stones may then pass in the urine. Stones that cannot
be broken into pieces by these methods, or that the
patient cannot pass, may have to be surgically removed.

PERIODICALS

Schwartz, B.F., and M.L. Stoller. ‘‘The vesical calculus.’’
Urologic Clinics of North America 27 (May 2000):
333-46.
ORGANIZATIONS

American Foundation for Urologic Disease. 1128 North
Charles Street, Baltimore, Maryland 21201. (410)
468-1800. Fax: (410) 468-1808. <http://www.afud.
org/>.
OTHER

‘‘Bladder Stones.’’ MEDLINEplus Health Information.
May 12, 2001. <http://medlineplus.adam.com/ency/
article/001275.htm>.

Paul A. Johnson, Ed.M.

Alternative treatment
Traditional herbal remedies for bladder stones
include celery seed and horsetail. Also, because incomplete bladder emptying may cause bladder stones, many
patients may benefit from methods and remedies aimed
at improving overall bladder function. These include
Kegel exercises, which are used to strengthen the
muscles involved in urination; herbal supplements
(cornsilk, hydrangea, juniper berries, parsley, and uva
ursi) used to increase urine flow and flush out sediment
from the bladder; and, the consumption of cranberry
juice and/or fresh, unsweetened, lemon juice.
Cranberry juice helps to control urinary tract infection
and contains a chemical that coats the walls of the
bladder, making them more resistant to infection.
Lemon juice helps to flush out the urinary system.

Prognosis
Most bladder stones can be, and are, passed out of
the body in the urine without any permanent damage
to the bladder or the rest of the urinary tract.
However, most bladder stones arise from an underlying medical condition. Therefore, if this medical
condition is not corrected approximately half of all
patients will experience a recurrence of bladder stones
within five years.

Prevention
Bladder stones may, in some cases, be prevented
by the patient receiving prompt medical treatment for
568

I Bladder training
Definition
Bladder training is a behavioral modification treatment technique for urinary incontinence that involves
placing a patient on a toileting schedule. The time
interval between urination is gradually increased in
order to train the patient to remain continent.

Purpose
Bladder training is used to treat urinary urge
incontinence. Urge incontinence occurs when an
individual feels a sudden need to urinate and cannot
control the urge to do so and, as a consequence, involuntarily loses urine before making it to the toilet.

Precautions
Incontinence may be controlled through a number of invasive and non-invasive treatment options,
including Kegel exercises, biofeedback, bladder
training, medication, insertable incontinence devices,
and surgery. Each patient should undergo a full
diagnostic work-up to determine the type and cause
of the incontinence in order to determine the best
course of treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Biofeedback—Biofeedback training monitors temperature and muscle contractions in the vagina to
help incontinent patients control their pelvic
muscles.
Pelvic muscle exercises—Exercises that tighten and
tone the pelvic floor, or perineal, muscles. Also
known as Kegel and PC muscle exercises.

be recommended to supplement the progress made
with bladder training.
Resources
ORGANIZATIONS

American Foundation for Urologic Disease. 1128 North
Charles St., Baltimore, MD 21201. (800) 242-2383.
<http://www.afud.org>.
National Association for Continence. P.O. Box 8310,
Spartanburg, SC 29305-8310. (800) 252-3337. <http://
www.nafc.org>.

Paula Anne Ford-Martin

Description
Bladder training may be prescribed and implemented by a general physician, urologist, or urogynecologist. A urination schedule is created for the patient.
The schedule typically starts out with fairly short intervals between bathroom breaks (e.g., an hour). As soon
as the patient is able to consistently remain continent
for several days at a certain toileting time interval, the
time span is increased. Bladder training continues until
the patient regularly achieves continence at a time
interval he/she feels comfortable with.

Preparation
A complete evaluation to determine the cause of
urinary incontinence is critical to proper treatment.
A thorough medical history and physical examination
should be performed on patients considering bladder
training. Diagnostic testing may include x rays, ultrasound, urine tests, and a physical examination of
the pelvis. It may include a series of exams called
urodynamic testing that measure bladder pressure
and capacity and the urinary flow. The patient may
also be asked to keep a diary of their urination output
and frequency and episodes of incontinence over a
period of several days or a week.

Risks
Bladder training may not be successful in all
patients with urge incontinence. Patients who demonstrate a strong desire to control their continence and
are committed to sticking with a training program
tend to have the most success with bladder training.

Normal results
Patients who undergo successful bladder training
gain complete or improved control over their urination. In some cases, additional alternate treatment
such as biofeedback or pelvic muscle exercises may
GALE ENCYCLOPEDIA OF MEDICINE

Blastomyces dermatitidis see Blastomycosis

I Blastomycosis
Definition
Blastomycosis is an infection caused by inhaling
microscopic particles (spores) produced by the fungus
Blastomyces dermatitidis. Blastomycosis may be limited
to the lungs or also involve the skin and bones. In its
most severe form, the infection can spread throughout
the body and involve many organ systems (systemic).

Description
Blastomycosis is a fungal infection caused by
Blastomyces dermatitidis. Although primarily an airborne disease, farmers and gardeners may become
infected from contact with spores in the soil through
cuts and scrapes. The fungus that causes the disease is
found in moist soil and wood in the southeastern
United States, the Mississippi River valley, southern
Canada, and Central America. Blastomycosis is also
called Gilchrist’s disease, Chicago disease, or North
American blastomycosis. Another South and Central
American disease, paracoccidioidomycosis, is sometimes called South American blastomycosis, but
despite the similar name, this disease is substantially
different from North American blastomycosis. Canine
blastomycosis, a common dog disease, is caused by the
same fungus that infects humans. However, people do
not get this disease from their dogs except only very
rarely through dog bites.
Blastomycosis is a rare disease infecting only
about 4 in every 100,000 people. It is at least six
times more common in men than in women and
tends to more often infect children and individuals in
the 30–50 year old age group. People who have
569

Blastomycosis

KEY TERMS

Blastomycosis

KEY TERMS
Abscess—An area of inflamed and injured body
tissue that fills with pus.
Acidophilus—The bacteria called Lactobacillus
acidophilus that is usually found in yogurt.
Alveoli—Small air pockets in the lungs that
increase the surface area for oxygen absorption.
Bifidobacteria—A group of bacteria normally present in the intestine. Commercial supplements containing these bacteria are available.
Blastomycosis is usually attributed to contact with yeast-like
fungi. (Custom Medical Stock Photo. Reproduced by permission.)

diabetes mellitus or who are taking drugs that suppress the immune system (immunocompromised) are
more likely to develop blastomycosis. Although people with AIDS can get blastomycosis because of their
weakened immune system, blastomycosis has not been
one of the more common fungal infections associated
with AIDS.

Causes and symptoms
Once inhaled, the spores of B. dermatitidis can
lodge in the lungs and cause a localized inflammation.
This is known as primary pulmonary blastomycosis.
The disease does not spread from one person to
another. In the early stages, symptoms may include a
dry cough, fever, heavy sweating, fatigue, and a general
feeling of ill health. In approximately 25% of blastomycosis cases, only the lungs are affected. As the disease progresses, small lesions form in the lungs causing
the air sacs deep within the lungs (alveoli) to break
down and form small cavities.
In another 35%, the disease involves both the
lungs and the skin. Bumps develop on the skin,
gradually becoming small, white, crusted blisters
filled with pus. The blisters break open, creating
abscesses that do not heal. Approximately 19% of
infected people have skin sores without infection in
the lungs.
The remaining approximately 20% of the
infected population has blastomycosis that has
spread or disseminated to other systems of the
body. Symptoms may include pain and lesions on
one or more bones, the male genitalia, and/or parts
of the central nervous system. The liver, spleen,
lymph nodes, heart, adrenal glands, and digestive
system may also be infected.
570

Biopsy—The removal of a tissue sample for diagnostic purposes.
Immunocompromised—A state in which the
immune system is suppressed or not functioning
properly.
Spores—The small, thick-walled reproductive
structures of fungi.
Sputum—Mucus and other matter coughed up
from airways.
Systemic—Not localized to a single area of the
body but, instead, involving one or more body
systems.

Diagnosis
A positive diagnosis of blastomycosis is made when
the fungus B. dermatitidis is identified by direct microscopic examination of body fluids such as sputum and
prostate fluid or in tissue samples (biopsies) from the
lung or skin. Another way to diagnose blastomycosis is
to culture and isolate the fungus from a sample of
sputum. Chest x rays are used to assess lung damage,
but alone cannot lead to a definitive diagnosis of blastomycosis because any damage caused by other diseases, such as by pneumonia or tuberculosis, may
appear look on the x ray. Because its symptoms vary
widely, blastomycosis is often misdiagnosed.

Treatment
Blastomycosis must be treated or it will gradually
lead to death. Treatment with the fungicidal drug
ketoconazole (Nizoral) taken orally is effective in
about 75% of patients. Amphotericin B (Fungizone)
given intravenously is also very effective, but it has
more toxic side effects than ketoconazole. Treatment
with amphotericin B usually requires hospitalization,
and the patient may also receive other drugs to minimize the its side effects.
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment for fungal infections
focuses on creating an internal environment where
the fungus cannot survive. This is accomplished by
eating a diet low in dairy products, sugars, including
honey and fruit juice, and foods like beer that contain
yeast. This is complemented by a diet consisting, in
large part, of uncooked and unprocessed foods.
Supplements of vitamins C, E, A-plus, and B complex
may also be useful. Lactobacillus acidophilus and
Bifidobacterium will replenish the good bacteria in
the intestines. Some antifungal herbs, like garlic
(Allium sativum), can be consumed in relatively large
doses and for an extended period of time in order to
increase effectiveness. A variety of antifungal herbs,
such as myrrh (Commiphora molmol), tea tree oil
(Melaleuca spp.), citrus seed extract, pau d’arco tea
(Tabebuia impetiginosa), and garlic may also be
applied directly to the infected skin.

Prognosis
Left untreated, blastomycosis gradually leads to
death. When treated, however, patients begin to
improve within one week and, with intensive treatment, may be cured within several weeks. The highest
rate of recovery is among patients who only have skin
lesions. People with the disseminated form of the disease are least likely to be cured and and most likely to
suffer a relapse.

Prevention
Because the fungus that causes blastomycosis is
airborne and microscopic, the only form of prevention is to avoid visiting areas where it is found in the
soil. For many people this is impractical. Since the
disease is rare, people who maintain general good
health do not need to worry much about infection.
Resources
ORGANIZATIONS

National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

I Bleeding time
Definition
Bleeding time is a crude test of hemostasis (the arrest
or stopping of bleeding). It indicates how well platelets
interact with blood vessel walls to form blood clots.

Purpose
Bleeding time is used most often to detect qualitative defects of platelets, such as Von Willebrand’s
disease. The test helps identify people who have
defects in their platelet function. This is the ability
of blood to clot following a wound or trauma.
Normally, platelets interact with the walls of blood
vessels to cause a blood clot. There are many factors
in the clotting mechanism, and they are initiated by
platelets. The bleeding time test is usually used on
patients who have a history of prolonged bleeding
after cuts, or who have a family history of bleeding
disorders. Also, the bleeding time test is sometimes
performed as a preoperative test to determine a
patient’s likely bleeding response during and after
surgery. However, in patients with no history of
bleeding problems, or who are not taking antiinflammatory drugs, the bleeding time test is not
usually necessary.

Precautions
Before administering the test, patients should be
questioned about what medications they may be
taking. Some medications will adversely affect the
results of the bleeding time test. These medications
include anticoagulants, diuretics, anticancer drugs, sulfonamides, thiazide, aspirin and aspirin-containing
preparations, and nonsteroidal anti-inflammatory
drugs. The test may also be affected by anemia (a
deficiency in red blood cells). Since the taking of
aspirin or related drugs are the most common cause
of prolonged bleeding time, no aspirin should be taken
two weeks prior to the test.

Description

OTHER

‘‘Blastomycosis.’’ Vanderbilt University Medical Center.
<http://www.mc.vanterbilt.edu/peds/pid/infect/
blastomy.html>.

Tish Davidson, A.M.

Bleeding disorders see Coagulation
disorders
GALE ENCYCLOPEDIA OF MEDICINE

There are four methods to perform the bleeding
test. The Ivy method is the traditional format for this
test. In the Ivy method, a blood pressure cuff is
placed on the upper arm and inflated to 40 mM
Hg. A lancet or scalpel blade is used to make a stab
wound on the underside of the forearm. An automatic, spring-loaded blade device is most commonly
used to make a standard-sized cut. The area stabbed
571

Bleeding time

Alternative treatment

Bleeding varices

Normal results

KEY TERMS
Hemostasis—The stopping of bleeding or blood
flow through a blood vessel or organ.

is selected so that no superficial or visible veins are
cut. These veins, because of their size, may have
longer bleeding times, especially in people with
bleeding defects. The time from when the stab
wound is made until all bleeding has stopped is
measured and is called the bleeding time. Every 30
seconds, filter paper or a paper towel is used to draw
off the blood. The test is finished when bleeding has
stopped completely.
The three other methods of performing the bleeding test are the template, modified template, and Duke
methods. The template and modified template methods are variations of the Ivy method. A blood pressure
cuff is used and the skin on the forearm prepared as in
the Ivy method. A template is placed over the area to
be stabbed and two incisions are made in the forearm
using the template as a location guide. The main difference between the template and the modified method
is the length of the cut made.
For the Duke method, a nick is made in an ear
lobe or a fingertip is pricked to cause bleeding. As in
the Ivy method, the test is timed from the start of
bleeding until bleeding is completely stopped. The
disadvantage to the Duke method is that the pressure
on the blood veins in the stab area is not constant and
the results achieved are less reliable. The advantage to
the Duke method is that no scar remains after the test.
The other methods may result in a tiny, hairline scar
where the wound was made. However, this is largely a
cosmetic concern.

Preparation
There is no special preparation required of the
patient for this test. The area to be stabbed should be
wiped clean with an alcohol pad. The alcohol should
be left on the skin long enough for it to kill bacteria at
the wound site. The alcohol must be removed before
stabbing the arm because alcohol will adversely affect
the tests results by inhibiting clotting.

Aftercare
If a prolonged bleeding time is caused by unknown
factors or diseases, further testing is required to identify
the exact cause of the bleeding problem.
572

A normal bleeding time for the Ivy method is less
than five minutes from the time of the stab until all
bleeding from the wound stops. Some texts extend the
normal range to eight minutes. Normal values for the
template method range up to eight minutes, while for
the modified template methods, up to 10 minutes is
considered normal. Normal for the Duke method is
three minutes.

Abnormal results
A bleeding time that is longer than normal is an
abnormal result. The test should be stopped if the
patient hasn’t stopped bleeding by 20-30 minutes.
Bleeding time is longer when the normal function of
platelets is impaired, or there are a lower-than-normal
number of platelets in the blood.
A longer-than-normal bleeding time can indicate
that one of several defects in hemostasis is present,
including severe thrombocytopenia, platelet dysfunction, vascular defects, Von Willebrand’s disease, or
other abnormalities.
Resources
BOOKS

Henry, J. B. Clinical Diagnosis and Management by
Laboratory Methods. Philadelphia: W. B. Saunders Co.,
1996.

John T. Lohr, PhD

I Bleeding varices
Definition
Bleeding varices are bleeding, dilated (swollen)
veins in the esophagus (gullet), or the upper part of
the stomach, caused by liver disease.

Description
Engorged veins are called varices (plural of varix).
Varices may occur in the lining of the esophagus, the
tube that connects the mouth to the stomach, or in the
upper part of the stomach. Such varices are called
esophageal varices. These varices are fragile and can
bleed easily because veins are not designed to handle
high internal pressures.
GALE ENCYCLOPEDIA OF MEDICINE

Liver disease often causes an increase in the
blood pressure in the main veins that carry blood
from the stomach and intestines to the liver (portal
veins). As the pressure in the portal veins increases,
the veins of the stomach and esophagus swell, until
they eventually become varices. Bleeding varices are a
life-threatening complication of this increase in blood
pressure (portal hypertension). The most common
cause of bleeding varices is cirrhosis of the liver
caused by chronic alcohol abuse or hepatitis.
Bleeding varices occur in approximately one in
every 10,000 people.
Symptoms of bleeding varices include:


vomiting blood, sometimes in massive amounts



black, tarry stools



decreased urine output



excessive thirst



nausea



vomiting



blood in the vomit

If bleeding from the varices is severe, a patient
may go into shock from the loss of blood, characterized by pallor, a rapid and weak pulse, rapid and
shallow respiration, and lowered systemic blood
pressure.

Diagnosis
Bleeding varices may be suspected in a patient
who has any of the above-mentioned symptoms, and
who has either been diagnosed with cirrhosis of the
liver or who has a history of prolonged alcohol abuse.
The definitive diagnosis is established via a specialized
type of endoscopy, namely, esophagogastroduodenoscopy (EGD), a procedure that involves the visual
examination of the lining of the esophagus, stomach,
and upper duodenum with a flexible fiberoptic
endoscope.

KEY TERMS
Cirrhosis of the liver—A type of liver disease, most
often caused by chronic alcohol abuse. It is
characterized by scarring of the liver, which
leads to an increase in the blood pressure in the
portal veins.
Endoscopy—Medical imaging technique for visualizing the interior of a hollow organ.
Esophagus—The tube in the body which takes food
from the mouth to the stomach.
Esophagogastroduodenoscopy (EGD)—An imaging test that involves visually examining the lining
of the esophagus, stomach, and upper duodenum
with a flexible fiberoptic endoscope.
Portal hypertension—Portal hypertension forces
the blood flow backward, causing the portal veins
to enlarge and the emergence of bleeding varices
across the esophagus and stomach from the
pressure in the portal vein. Portal hypertension is
most commonly caused by cirrhosis, but can also
be seen in portal vein obstruction from unknown
causes.
Portal veins—The main veins that carry blood from
the stomach and intestines to the liver.
Shock—A state of depression of the vital processes
of the body characterized by pallor, a rapid and
weak pulse, rapid and shallow respiration, and
lowered blood pressure. Shock results from severe
trauma, such as crushing injuries, hemorrhage,
burns, or major surgery.
Transjugular intrahepatic portosystemic shunt
(TIPS)—A transjugular intrahepatic portosystemic
shunt (TIPS) is a radiology procedure in which a
tubular device is inserted in the middle of the liver
to redirect the blood flow.
Varices—A type of varicose vein that develops in
veins in the linings of the esophagus and upper
stomach when these veins fill with blood and
swell due to an increase in blood pressure in the
portal veins.

Treatment
The objective during treatment of bleeding
varices is to stop and/or prevent bleeding and to
restore/maintain normal blood circulation throughout the body. Patients with severe bleeding should be
treated in intensive care since uncontrolled bleeding
can lead to death.
Initial treatment of bleeding varices begins
with standard resuscitation, including intravenous
GALE ENCYCLOPEDIA OF MEDICINE

fluids and blood transfusions as needed. Definitive
treatment is usually endoscopic, with the endoscope used to locate the sites of the bleeding. An
instrument, inserted along with the endoscope, is
used either to inject these sites with a clotting agent
or to tie off the bleeding sites with tiny rubber
bands.
573

Bleeding varices

Causes and symptoms

Blepharoplasty

Repeated endoscopic treatments (usually four/
six) are generally required to eliminate the varices
and to prevent the recurrence of bleeding. These endoscopic techniques are successful in about 90 percent
of cases.
Patients who cannot be treated endoscopically
may be considered for an alternative procedure called
TIPS (transjugular intrahepatic portosystemic shunt).
This procedure involves placing a hollow metal
tube (shunt) in the liver connecting the portal veins
with the hepatic veins (veins that leave the liver and
drain to the heart). This shunt lowers the pressure in
the portal veins and prevents bleeding and portal
hypertension. The TIPS procedure is performed by a
radiologist and has become an accepted method for
reducing portal vein pressure since 1992. Although the
procedure continues to evolve, TIPS can routinely be
created in more than 93% of patients.
Medications aimed at controlling bleeding
may also be prescribed. These include propanolol,
vasopressin, octreotide acetate, and isosorbide
mononitrate.

Alternative treatment
Some alternative treatments are aimed at preventing the cirrhosis of the liver that often causes bleeding
varices and most are effective. However, once a patient
has reached the bleeding varice stage, standard intervention to stop the bleeding is required or the patient
may die.

Prognosis
Bleeding varices represent one of the most feared
complications of portal hypertension. They contribute
to the estimated 32,000 deaths per year attributed to
cirrhosis. Half or more of patients who survive episodes
of bleeding varices are at risk of renewed esophageal
bleeding during the first one to two years. The risk of
recurrence can be lowered by endoscopic and drug
treatment. Prognosis is usually more related to the
underlying liver disease. Approximately 30 to 50 percent
of people with bleeding varices will die from this condition within the six weeks of the first bleeding episode.

Prevention
The best way to possibly prevent the development
or recurrence of bleeding varices is to eliminate the risk
factors for cirrhosis of the liver. The most common
cause of cirrhosis is prolonged alcohol abuse, and alcohol consumption must be completely eliminated. People
574

with hepatitis B or hepatitis C also have an increased
risk of developing cirrhosis of the liver. Vaccination
against hepatitis B and avoidance of intravenous drug
usage reduce the risk of contracting hepatitis.
Resources
BOOKS

Shannon, Joyce Brennfleck, editor. Liver Disorders
Sourcebook. Detroit, MI: Omnigraphics, Inc., 2000.
PERIODICALS

Burroughs, Andrew K. and David Patch. ‘‘Primary
prevention of bleeding from esophageal varices.’’ New
England Journal of Medicine 340 (April 1, 1999): 1033-5.
Hegab, Ahmed M., and Velimir A. Luketic. ‘‘Bleeding
esophageal varices: How to treat this dreaded complication of portal hypertension.’’ Postgraduate Medicine
109 (February 2001): 75-89.
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
OTHER

Goff, John. ‘‘Portal hypertensive bleeding.’’ May 12, 2001.
<http://www.nysge.org/PostGrad1999/
Goff_VaricealBleeding.htm>.

Paul A. Johnson, Ed.M.

Blepharitis see Eyelid disorders

I Blepharoplasty
Definition
Blepharoplasty is a cosmetic surgical procedure
that removes fat deposits, excess tissue, or muscle
from the eyelids to improve the appearance of the eyes.

Purpose
The primary use of blepharoplasty is for improving the cosmetic appearance of the eyes. In some older
patients, however, sagging and excess skin surrounding the eyes can be so extensive that it limits the range
of vision. In those cases, blepharoplasty serves a more
functional purpose.

Precautions
Before performing blepharoplasty, the surgeon will
assess whether the patient is a good candidate for the
GALE ENCYCLOPEDIA OF MEDICINE

Blepharoplasty

Pinching the
redundant skin

Cutting the skin off

Closing the incisions

Blepharoplasty is one of the most common cosmetic surgical procedures. The illustration above depicts a procedure to
eliminate dermochalasia, or baggy skin around the eyes. (Illustration by Electronic Illustrators Group.)

treatment. A good medical history is important. The
surgeon will want to know about any history of thyroid
disease, hypertension, or eye problems, which may
increase the risk of complications.

Description
Blepharoplasty can be performed on the upper or
lower eyelid; it can involve the removal of excess skin
and fat deposits and the tightening of selected muscles
surrounding the eyelids. The goal is to provide a more
youthful appearance.
The surgeon will begin by deciding whether excess
skin, fat deposits, or muscle looseness are at fault.
While the patient is sitting upright, the surgeon will
mark on the skin where incisions will be made. Care
will be taken to hide the incision lines in the natural
skin folds above and below the eye. The patient then
receives injections of a local anesthetic to numb the
pain. Many surgeons also give the patient a sedative
intravenously during the procedure.
After a small, crescent-shaped section of eyelid
skin is removed, the surgeon will work to tease out
small pockets of fat that have collected in the lids. If
muscle looseness is also a problem, the surgeon may
trim tissue or add a stitch to pull it tighter. Then the
incision is closed with stitches.
In some patients, fat deposits in the lower eyelid
may be the only or primary problem. Such patients
may be good candidates for transconjunctival blepharoplasty. In this procedure the surgeon makes no
incision on the surface of the eyelid, but instead enters
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Ectropion—A complication of blepharoplasty, in
which the lower lid is pulled downward, exposing
the surface below.
Intravenous sedation—A method of injecting a
fluid sedative into the blood through the vein
Retrobulbar hematoma—A rare complication of
blepharoplasty, in which a pocket of blood forms
behind the eyeball.
Transconjuctival blepharoplasty—A type of blepharoplasty in which the surgeon makes no
incision on the surface of the eyelid, but,
instead, enters from behind to tease out the fat
deposits.

from behind to tease out the fat deposits from a small
incision. The advantage of this procedure is that there
is no visible scar.

Preparation
Prior to surgery, patients meet with their surgeon to discuss the procedure, clarify the results
that can be achieved, and discuss the potential problems that might occur. Having realistic expectations is important in any cosmetic procedure.
Patients will learn, for example, that although blepharoplasty can improve the appearance of the eyelid, other procedures, such as a chemical peel, will be
575

Blood-viscosity reducing drugs

necessary to reduce the appearance of wrinkles
around the eye. Some surgeons prescribe vitamin C
and vitamin K for 10 days prior to surgery in the
belief that this helps the healing process. Patients are
also told to stop smoking in the weeks before and
after the procedure, and to refrain from alcohol and
aspirin.

Aftercare
An antibiotic ointment is applied to the line of
stitches for several days after surgery. Patients also
take an antibiotic several times a day to prevent
infection. Ice-cold compresses are applied to the
eyes continuously for the first day following surgery, and several times a day for the next week or
so, to reduce swelling. Some swelling and discoloration around the eyes is expected with the procedure.
Patients should avoid aspirin or alcoholic beverages
for one week and should limit their activities,
including bending, straining, and lifting. The
stitches are removed a few days after surgery.
Patients can generally return to their usual activities
within a week to 10 days.

Risks
As with any surgical procedure, blepharoplasty can lead to infection and scarring. Good
care of the wound following surgery can minimize
these risks. In cases where too much skin is
removed from the eyelids, the patient may have
difficulty closing his eyes. Dry eye syndrome may
develop, requiring the use of artificial tears to
lubricate the eye. In a rare complication, called
retrobulbar hematoma, a pocket of blood forms
behind the eyeball.

Normal results
Most patients can expect good results from blepharoplasty, with the removal of excess eyelid skin
and fat producing a more youthful appearance.
Some swelling and discoloration is expected immediately following the procedure, but this clears in time.
Small scars will be left where the surgeon has made
incisions; but these generally lighten in appearance
over several months, and, if placed correctly, will not
be readily noticeable.

Abnormal results
As noted, if too much excess skin is removed
from the upper eyelid, the patient may be unable to
576

close his eyes completely; another surgery to correct
the defect may be required. Similarly, too much skin
can be removed from the lower eyelid, allowing too
much of the white of the eye (the sclera) to show. In
extreme cases, the lower lid may be pulled down too
far, revealing the underlying tissue. Called an ectropion, this, too, may require a second, corrective
surgery. The eye’s ability to make tears may also be
compromised, leading to dry eye syndrome. Dry eye
syndrome is potentially dangerous; in rare cases
it leads to damage to the cornea of the eye and
vision loss.
Resources
ORGANIZATIONS

American Society for Dermatologic Surgery. 930 N.
Meacham Road, P.O. Box 4014, Schaumburg, IL
60168-4014. (847) 330-9830. <http://www.asdsnet.org>.
American Society of Plastic and Reconstructive Surgeons.
44 E. Algonquin Rd., Arlington Heights, IL 60005.
(847) 228-9900. <http://www.plasticsurgery.org>.

Richard H. Camer

Blindness see Visual impairment

I Blood-viscosity reducing drugs
Definition
Blood-viscosity reducing drugs are medicines that
improve blood flow by making the blood less viscous
(sticky).

Purpose
The main use of blood-viscosity reducing drugs
is to relieve painful leg cramps caused by poor circulation, a condition called intermittent claudication.
Physicians also may prescribe this medicine for other
conditions, including stroke, impotence, male infertility, Raynaud’s disease, and nerve and circulation
problems caused by diabetes.

Description
Blood-viscosity reducing drugs are available only
with a physician’s prescription and come in extendedrelease tablet form. Examples of blood-viscosity reducing
drugs are pentoxifylline (Trental) and oxypentifylline.
GALE ENCYCLOPEDIA OF MEDICINE

Raynaud’s disease—A blood vessel disorder in
which the fingers and toes become numb and turn
white when exposed to cold.

Recommended dosage
The usual dosage for adults is 400 mg, two to three
times a day, with meals. However, the dose may be
different for different patients. Check with the physician who prescribed the drug or the pharmacist who
filled the prescription for the correct dosage. Dosages
for children must be determined by a physician.
Taking an antacid with this medicine may help
prevent upset stomach.



kidney disease



liver disease

Blood clots

KEY TERMS

Side effects
Minor discomforts, such as dizziness, headache,
upset stomach, nausea, or vomiting usually go away
as the body adjusts to the drug and do not require
medical treatment unless they persist or they interfere
with normal activities.
More serious side effects are rare. However, if
these or any other unusual or troublesome symptoms
occur, check with the physician who prescribed the
medicine as soon as possible:


chest pain



irregular heartbeat

Interactions
Precautions
This medicine may relieve leg pain that results
from poor circulation, but it should not be considered
a substitute for other treatments the physician recommends, such as physical therapy or surgery.
This medicine may take several weeks to produce
noticeable results. Be sure to keep taking it as directed,
even if it doesn’t seem to be helping.
Patients being treated with this medicine should
not smoke, as smoking may worsen the conditions for
which the medicine is prescribed.
Anyone who has had unusual reactions to pentoxifylline, aminophylline, caffeine, dyphylline, ethylenediamine (contained in aminophylline), oxtriphylline,
theobromine, or theophylline in the past should let his
or her physician know before taking a blood-viscosity
reducing drug. The physician should also be told
about any allergies to foods, dyes, preservatives, or
other substances.

Blood-viscosity reducing drugs may interact
with a other medicines, changing the effects of one
or both of the drugs or increasing the risk of side
effects. Anyone who takes blood-viscosity reducing
drugs should let the physician know all other prescription or nonprescription (over-the-counter)
medicines he or she is taking. Among the drugs
that may interact with blood-viscosity reducing
drugs are:


anticoagulants such as warfarin (Coumadin)(also
called blood thinners or clot inhibitors)



calcium channel blockers such as diltiazem
(Cardizem), used to treat high blood pressure



angiotensin-converting enzyme (ACE) inhibitors
such as enalapril (Vasotec), used to treat high blood
pressure



theophylline (Theo-Dur)



medicines such as cimetidine (Tagamet), taken for
ulcers or heartburn

Women who are pregnant or breastfeeding or who
may become pregnant should check with their physicians before using a blood-viscosity reducing drug.

Nancy Ross-Flanigan

Older people may be especially sensitive to the
effects of this medicine, which may increase the chance
of side effects.
Before using blood-viscosity reducing drugs, people with any of these medical problems should make
sure their physicians are aware of their conditions:


recent stroke



any condition in which there is an increased chance
of bleeding

GALE ENCYCLOPEDIA OF MEDICINE

I Blood clots
Definition
A blood clot is a thickened mass in the blood
formed by tiny substances called platelets. Clots form
to stop bleeding, such as at the site of cut. But clots
577

Blood clots

should not form when blood is moving through the
body; when clots form inside blood vessels or when
blood has a tendency to clot too much, serious health
problems can occur.

Description
As soon as a blood vessel wall is damaged—by a
cut or similar trauma—a series of reactions normally
takes place to activate platelets to stop the bleeding.
Platelets are the tiny particles in the blood released
into the bone marrow that gather together and form
a barrier to further bleeding. Several proteins in the
body are involved in the platelets clotting process.
Chief among these proteins are collagen, thrombin,
and von Willebrand factor. Collagen and thrombin
help platelets stick together. As platelets gather at
the site of injury, they change in shape from round
to spiny, releasing proteins and other substances
that help catch more platelets and clotting proteins.
This enlarges the plug that becomes a blood
clot. Formation of blood clots also is called
‘‘coagulation’’.
The series of reactions that cause proteins and
platelets to create blood clots also are balanced by
other reactions that stop the clotting process and dissolve clots after the blood vessel has healed. If this
control system fails, minor blood vessel injuries can
trigger clotting throughout the body. The tendency to
clot too much is called ‘‘hypercoagulation’’. Anytime
clots form inside blood vessels, they can lead to serious
complications.
The formation of a clot in a blood vessels may be
called thrombophlebitis. The term refers to swelling of
one or more veins caused by a blood clot. Although
some clots occur in the arms or small, surface blood
vessels, most occur in the lower legs. When the blood
clot occurs in a deep vein, it is called deep vein thrombosis, or DVT. As many as one of every 1,000
Americans develops DVT each year. The danger of
DVT comes when pieces of the clot, known as emboli,
break off and travel through the bloodstream to an
artery.
A blood clot that blocks an artery to the brain can
cause a stroke. If the clot blocks blood flow to the
lungs pulmonary embolism can occur. A blood clot
that blocks a coronary artery can cause a heart attack.
Certain people are at higher risk for blood clots than
others; surgery, some injuries, childbirth and lying or
sitting still for extended periods of time put people at
higher risk, as do inherited disorders. Once a person
has a blood clot, he or she may have to take bloodthinning drugs to prevent clots from recurring. Men
578

KEY TERMS
Central venous access catheter—A tube placed
just beneath the skin to allow doctors and nurses
constant and pain-free access to the veins, often
when a patient is in the hospital or has a chronic
disease such as cancer. The doctors and nurses can
draw blood and give medications and nutrients
through the catheter.
Genetic—A trait or condition that is acquired
or inherited because it was related to genes and
DNA.
Pulmonary embolism—The sudden obstruction of
a pulmonary (lung) artery or one of its branches by
an abnormal particle (such as a blood clot) floating
in the blood.

and women are at similar risk for blood clots. A recent
study in Austria found that men run a higher risk of
recurring blood clots than women, though the reason
is unknown.

Causes and symptoms
Many causes can lead to blood clots, some
genetic and some environmental. An environmental
cause of DVT is prolonged inactivity. For instance,
having to sit in a car or airplane for a long period of
time decreases blood flow in the lower legs. Recent
studies have shown that 1% of air travelers develop
blood clots, usually on long flights of five hours or
more. However, one study in 2004 found that air
travelers developed clots on flights as short as three
hours, though they often dissolved naturally and did
not lead to complications. Other environmental
causes of blood clots include use of hormone replacement therapy to ease menopausal symptoms, oral
contraceptives for birth control, pregnancy (and a
childbirth within the past six weeks), recent surgery
or procedures involving use of a central venous
access catheter, and cancer. Smoking also is an
important and preventable environmental risk for
blood clots.
Some people are born with a higher risk for blood
clots. Hypercoagulation disorders are genetic conditions. Usually the body doesn t produce enough of
the proteins involved in the clotting process, so they
cannot do their job to stop the clotting; in other cases,
they have an extra protein that causes too much
clotting.
GALE ENCYCLOPEDIA OF MEDICINE



Pain or tenderness in the affected area.



Warmth or redness of the skin in the affected area.



Sudden swelling in the affected limb.

Additional symptoms may indicate serious complications of blood clots such as pulmonary embolism,
stroke, and heart attack. If vein swelling or pain are
accompanied by high fever or shortness of breath,
rapid pulse, or chest pain, or other symptoms that
may indicate stroke, heart attack, or pulmonary
embolism, it is advised to go to an emergency room
immediately.

Diagnosis
A physician will diagnose blood clots based on
patient history and one of several diagnostic imaging
exams. The patient’s history will help determine possible risk factors that may lead to suspected blood
clots. In addition to family history or known genetic
disorders, the patient may mention an environmental
factor such as recent air travel or use of high-risk
mediations.
To help get a picture of suspected clots inside the
veins, the first test chosen normally is an ultrasound.
Doppler or duplex ultrasound uses sound waves that
travel through tissue and reflect back. A computer
transforms the sound waves into moving images on
the screen that may show the clot, as well as blood flow
near the clot and any abnormalities. Ultrasound does
not use x rays and is a noninvasive method. Computed
tomography (CT) scans also might be used to image
the blood vessels. It is similar to x rays, except the
images are much like cross-section slices with greater
detail that can be computerized and even viewed threedimensionally. A special dye called a contrast agent
may be injected before the exam to help highlight the
veins. Magnetic resonance angiography uses magnetic
resonance imaging (MRI) to image the blood vessels.
It also may involve injection of a contrast dye.
Venography is less commonly used, but involves injecting a contrast and using x rays to image the vein.

Treatment
Medicines can help thin blood, making it less
likely to clot. The two most common blood thinners are heparin and warfarin. Heparin works
right away, keeping blood clots from growing. It
GALE ENCYCLOPEDIA OF MEDICINE

usually is injected. In recent years, more physicians have been prescribing low-molecular weight
heparin, purified versions of the drug that can be
given with less monitoring. Warfarin (coumadin)
often is used for long-term treatment of blood
clots and is taken orally. Patients must work closely with their physicians to constantly monitor its
effects and adjust dose if necessary. Too little
warfarin can lead to clotting, but too much can
thin the blood so much that causing life-threatening bleeding can occur. The same can be true of
low-molecular weight heparin when used on a
long-term, at-home basis.
Other treatments for blood clots include injecting
clot busting drugs directly into the clot through a
catheter, or in rare instances, installation of a filter to
block a clot from lodging in the lungs. Sometimes,
surgery also is needed to remove a clot blocking a
pelvic or abdominal vein or one that is chronic and
disabling. A cardiovascular surgeon or interventional
radiologist may perform balloon angioplasty or insert
a stent to open a narrowed or damaged vein. In an
emergency situation, a drug called tissue plasminogen
activator, or tPA, may be given to immediately dissolve a life-threatening blood clot to the brain or heart.
In 2004, the U.S. Food and Drug Administration
approved a new, small, corklike device that can be
used to remove blood clots from the brains of patients
who cannot receive clot-busting drugs.

Alternative treatment
Garlic is thought to lower blood clotting potential. Less evidence suggests onions and cayenne pepper
may help keep blood thin. New research from
Australia adds tomato juice to the list of potential
blood thinners. Subjects who drank a glass of tomato
juice a day reduced their risk for DVT, stroke and
cardiovascular disease. Research has shown that a
natural soy and pine product called pinokinase has
been effective in controlling DVT in air travelers.
Patients seeking alternative treatments for blood
clots should work with certified practitioners and
should inform their allopathic provider about their
alternative care.

Prognosis
If detected and controlled with medications,
blood clots can be safely managed. However, if the
clots become dislodged and travel to an artery, they
can cause nearly instant death. For instance, more
than 600,000 people have a pulmonary embolism
each year and more than 10% of them die from the
579

Blood clots

There may be no symptoms of blood clots until
they grow so large that they block the flow of blood
through the vein. Then, symptoms may develop suddenly around the area and include:

Blood count

embolism, most of them within 30 to 60 minutes after
symptoms start.

Definition

Prevention
Clots may be avoided by not smoking, and by not
using medications that add to the risk. Clotting can be
prevented by following physician recommendations
concerning medications. Sometimes, physicians will
prescribe special support stockings that prevent swelling and reduce chances of DVT. When taking an air
flight of six hours or longer, drinking plenty of fluids
to avoid dehydration, avoiding tight clothing around
the waist, and stretching calves every hour can help
prevent DVT. It is advised that those on long flights
get up and move about once an hour during the flight.
If not possible, moving the legs regularly while seated
by flexing the ankles, then pressing the feet against the
seat in the row ahead or on the floor can help stretch
the calves. A physician may advise those at high risk of
DVT wear support stockings during the flight or take
low-molecular weight heparin two to four hours
before departure.
Resources
PERIODICALS

One of the most commonly ordered clinical
laboratory tests, a blood count, also called a complete blood count (CBC), is a basic evaluation of
the cells (red blood cells, white blood cells, and platelets) suspended in the liquid part of the blood
(plasma). It involves determining the numbers, concentrations, and conditions of the different types of
blood cells.

Purpose
The CBC is a useful screening and diagnostic test
that is often done as part of a routine physical examination. It can provide valuable information about the
blood and blood-forming tissues (especially the bone
marrow), as well as other body systems. Abnormal
results can indicate the presence of a variety of conditions—including anemias, leukemias, and infections—
sometimes before the patient experiences symptoms of
the disease.

Description

‘‘Air Travel, Especially Long Flights, May Increase the Risk
of Blood Clots.’’ Women’s Health Weekly (Dec. 25,
2003):119.
‘‘In-flight Exercises for a Healthy Trip: Prevent
Dangerous Blood Clots With These Three Easy
Moves the Next Time You Fly.’’ Natural Health
(Jan–Feb. 2003):27.
Stephenson, Joan. ‘‘FDA Orders Estrogen Safety Warnings:
Agency Offers Guidance for HRT Use.’’ JAMA, The
Journal of the American Medical Association (Feb. 5,
2003):537–539.
‘‘Study Finds One Percent of Air Travelers Develop
Injurious Blood Clots.’’ Heart Disease Weekly (Jan. 25,
2004):41.
‘‘Tiny Corkscrew Clears Blood Clots.’’ Hematology Week
(Sept. 6, 2004):99.
ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105,
Behtesda, MD 20824-0105. 301-592-8573.
www.nhlbi.nih.gov.
Society of Interventional Radiology. 10201 Lee Highway,
Suite 500, Fairfax, VA 22030. 703-691-1805. http://
www.sirweb.org.
OTHER

Avoid Deep Vein Thrombosis: Keep the Blood Flowing. FDA
Web site, 2005. www.fda.gov/fdac/features/2004/
604_vein.html.

Teresa G. Odle
580

I Blood count

A complete blood count is actually a series of tests
in which the numbers of red blood cells, white blood
cells, and platelets in a given volume of blood are
counted. The CBC also measures the hemoglobin content and the packed cell volume (hematocrit) of the red
blood cells, assesses the size and shape of the red blood
cells, and determines the types and percentages of
white blood cells. Components of the complete blood
count (hemoglobin, hematocrit, white blood cells,
platelets, etc.) can also be tested separately, and are
sometimes done that way when a doctor wants to
monitor a specific condition, such as the white cell
count of a patient diagnosed with leukemia, or the
hemoglobin of a patient who has recently received a
blood transfusion. Because of its value, though, as an
indicator of a person’s overall health, the CBC package is most frequently ordered.
The blood count is performed relatively inexpensively and quickly. Most laboratories routinely use
some type of automated equipment to dilute the
blood, sample a measured volume of the diluted suspension, and count the cells in that volume. In addition to counting actual numbers of red cells, white
cells, and platelets, the automated cell counters also
measure the hemoglobin and calculate the hematocrit
and the red blood cell indices (measures of the size and
hemoglobin content of the red blood cells).
GALE ENCYCLOPEDIA OF MEDICINE

A white blood cell. (Photograph by Institut Pasteur, Phototake
NYC. Reproduced by permission.)

Technologists then examine a stained blood smear
under the microscope to identify any abnormalities
in the appearance of the red blood cells and to report
the types and percentages of white blood cells
observed.
The red blood cell (RBC) count determines the
total number of red cells (erythrocytes) in a sample of
blood. The red cells, the most numerous of the cellular elements, carry oxygen from the lungs to the
body’s tissues. Hemoglobin (Hgb) is the proteiniron compound in the red blood cells that enables
them to transport oxygen. Its concentration corresponds closely to the RBC count. Also closely tied
to the RBC and hemoglobin values is the hematocrit
(Hct), which measures the percentage of red blood
cells in the total blood volume. The hematocrit
(expressed as percentage points) is normally about
three times the hemoglobin concentration (reported
as grams per deciliter).
Red blood cell indices provide information
about the size and hemoglobin content of the red
cells. They are useful in differentiating types of anemias. The indices include four measurements that are
calculated using the RBC count, hemoglobin, and
hematocrit results. Mean corpuscular volume
(MCV) is a measurement of the average size of the
red blood cells and indicates whether that is small,
large or normal. The red blood cell distribution width
GALE ENCYCLOPEDIA OF MEDICINE

The white blood cell (WBC) count determines the
total number of white cells (leukocytes) in the blood
sample. Fewer in number than the red cells, WBCs
are the body’s primary means of fighting infection.
There are five main types of white cells (neutrophils,
lymphocytes, monocytes, eosinophils, and basophils), each of which plays a different role in responding to the presence of foreign organisms in the body.
A differential white cell count is done by staining a
smear of the patient’s blood with a Wright’s stain,
allowing the different types of white cells to be clearly
seen under the microscope. A technologist then
counts a minimum of 100 WBCs and reports each
type of white cell as a percentage of the total white
blood cells counted.
The platelet count is an actual count of the number
of platelets (thrombocytes) in a given volume of blood.
Platelets, the smallest of the cellular elements of blood,
are involved in blood clotting. Because platelets
can clump together, the automated counting method
is subject to a certain level of error and may not
be accurate enough for low platelet counts. For this
reason, very low platelet levels are often counted
manually.

Normal results
Blood count values can vary by age and sex. The
normal red blood cell count ranges from 4.2–5.4 million RBCs per microliter of blood for men and 3.6–5.0
million for women. Hemoglobin values range
from 14–18 grams per deciliter of blood for men and
12–16 grams for women. The normal hematocrit is
42–54% for men and 36–48% for women. The normal
number of white blood cells for both men and women
is approximately 4,000–10,000 WBCs per microliter of
blood.

Abnormal results
Abnormal blood count results are seen in a variety of conditions. One of the most common is anemias, which are characterized by low RBC counts,
hemoglobins, and hematocrits. Infections and leukemias are associated with increased numbers of
WBCs.
581

Blood count

(RDW) is an indication of the variation in RBC size.
Mean corpuscular hemoglobin (MCH) measures the
average amount (weight) of hemoglobin within a red
blood cell. A similar measurement, mean corpuscular
hemoglobin concentration (MCHC), expresses the
average concentration of hemoglobin in the red
blood cells.

Blood culture

Resources

KEY TERMS

BOOKS

Berkow, Robert, ed. Merck Manual of Medical Information.
Whitehouse Station, NJ: Merck Research
Laboratories, 1997.
Henry, J. B. Clinical Diagnosis and Management by Laboratory
Methods. New York: W. B. Saunders Co., 1996.

Karen A. Boyden

Blood crossmatching see Blood typing and
crossmatching

I Blood culture
Definition
A blood culture is done when a person has symptoms of a blood infection, also called bacteremia.
Blood is drawn from the person one or more times
and is tested in a laboratory to find and identify any
microorganism present and growing in the blood. If a
microorganism is found, more testing is done to determine the antibiotics that will be effective in treating the
infection.

Purpose
Bacteremia is a serious clinical condition and can
lead to death. To give the best chance for effective
treatment and survival, a blood culture is done as
soon as an infection is suspected.
Symptoms of bacteremia are fever, chills, mental
confusion, anxiety, rapid heart beat, hyperventilation,
blood clotting problems, and shock. These symptoms
are especially significant in a person who already has
another illness or infection, is hospitalized, or has
trouble fighting infections because of a weak immune
system. Often, the blood infection results from an
infection somewhere else in the body that has now
spread.
Additionally, blood cultures are done to find the
causes of other infections. These include bacterial
pneumonia (an infection of the lung), and infectious
endocarditis (an infection of the inner layer of the
heart). Both of these infections leak bacteria into the
blood.
After a blood infection has been diagnosed, confirmed by culture, and treated, an additional blood

582

Aerobe—Bacteria that require oxygen to live.
Anaerobe—Bacteria that live where there is no
oxygen.
Bacteremia—Bacteria in the blood.
Continuous bacteremia—A kind of bacteremia
where bacteria is always in the blood.
Intermittent bacteremia—A kind of bacteremia
where the bacteria enter the blood at various time
intervals.

culture may be done to make sure the infection is
gone.

Description
Culture strategies
There are many variables involved in performing
a blood culture. Before the person’s blood is drawn,
the physician must make several decisions based on a
knowledge of infections and the person’s clinical condition and medical history.
Several groups of microorganisms, including
bacteria, viruses, mold, and yeast, can cause blood
infections. The bacteria group can be further broken
down into aerobes and anaerobes. Most aerobes do
not need oxygen to live. They can grow with oxygen
(aerobic microbes) or without oxygen (anaerobic
microbes).
Based on the clinical condition of the patient, the
physician determines what group of microorganisms
is likely to be causing the infection and then orders
one or more specific types of blood culture, including
aerobic, anaerobic, viral, or fungal (for yeasts and
molds). Each specific type of culture is handled differently by the laboratory. Most blood cultures test for
both aerobic and anaerobic microbes. Fungal, viral,
and mycobacterial blood cultures can also be done,
but are less common.
The physician must also decide how many blood
cultures should be done. One culture is rarely
enough, but two to three are usually adequate.
Four cultures are occasionally required. Some factors influencing this decision are the specific microorganisms the physician expects to find based on the
person’s symptoms or previous culture results, and

GALE ENCYCLOPEDIA OF MEDICINE

The time at which the cultures are to be drawn is
another decision made by the physician. During
most blood infections (called intermittent bacteremia) microorganisms enter the blood at various
time intervals. Blood drawn randomly may miss the
microorganisms. Since microorganisms enter the
blood 30–90 minutes before the person’s fever
spikes, collecting the culture just after the fever
spike offers the best likelihood of finding the microorganism. The second and third cultures may be
collected at the same time, but from different places
on the person, or spaced at 30-minute or one-hour
intervals, as the physician chooses. During continuous bacteremia, such as infective endocarditis,
microorganisms are always in the blood and the
timing of culture collection is less important. Blood
cultures should always be collected before antibiotic
treatment has begun.
Laboratory analysis
Bacteria are the most common microorganisms
found in blood infections. Laboratory analysis of a
bacterial blood culture differs slightly from that of a
fungal culture and significantly from that of a viral
culture.
Blood is drawn from a person and put directly
into a blood culture bottle containing a nutritional
broth. After the laboratory receives the blood culture
bottle, several processes must be completed:


provide an environment for the bacteria to grow



detect the growth when it occurs



identify the bacteria that grow



test the bacteria against certain antibiotics to determine which antibiotic will be effective

There are several types of systems, both manual
and automated, available to laboratories to carry out
these processes.
The broth in the blood culture bottle is the first
step in creating an environment in which bacteria will
grow. It contains all the nutrients that bacteria need to
grow. If the physician expects anaerobic bacteria to
grow, oxygen will be kept out of the blood culture
bottle; if aerobes are expected, oxygen will be allowed
in the bottle.
The bottles are placed in an incubator and kept at
body temperature. They are watched daily for signs of
growth, including cloudiness or a color change in the

GALE ENCYCLOPEDIA OF MEDICINE

broth, gas bubbles, or clumps of bacteria. When there
is evidence of growth, the laboratory does a gram stain
and a subculture. To do the gram stain, a drop of
blood is removed from the bottle and placed on a
microscope slide. The blood is allowed to dry and
then is stained with purple and red stains and examined under the microscope. If bacteria are seen, the
color of stain they picked up (purple or red), their
shape (such as round or rectangular), and their size
provide valuable clues as to what type of microorganism they are and what antibiotics might work best. To
do the subculture, a drop of blood is placed on a
culture plate, spread over the surface, and placed in
an incubator.
If there is no immediate visible evidence of growth
in the bottles, the laboratory looks for bacteria by
doing gram stains and subcultures. These steps are
repeated daily for the first several days and periodically after that.
When bacteria grows, the laboratory identifies it
using biochemical tests and the gram stain. Sensitivity
testing, also called antibiotic susceptibility testing, is
also done. The bacteria are tested against many different antibiotics to see which antibiotics can effectively
kill it.
All information is passed on to the physician as
soon as it is known. An early report, known as a
preliminary report, is usually available after one day.
This report will tell if any bacteria have been found
yet, and if so, the results of the gram stain. The next
preliminary report may include a description of the
bacteria growing on the subculture. The laboratory
notifies the physician immediately when an organism
is found and as soon as sensitivity tests are complete.
Sensitivity tests may be complete before the bacteria
is completely identified. The final report may not be
available for five to seven days. If bacteria was
found, the report will include its complete identification and a list of the antibiotics to which the bacteria is
sensitive.
One automated system is considered one of
the most important recent technical advances in
blood cultures. It is called continuous-monitoring
blood culture systems (CMCCS). The instruments
automatically monitor the bottles containing the
patient blood for evidence of microorganisms, usually
every 10 minutes. Many data points are collected daily
for each bottle, and fed into a computer for analysis.
Sophisticated mathematical calculations can determine when microorganisms have grown. This, combined with more frequent blood tests, make it possible

583

Blood culture

whether or not the person has had recent antibiotic
therapy.

Blood donation and registry

to detect microbial growth earlier. In addition, all
CMBCS instruments have the detection system, incubator, and agitation unit in one unit.

Preparation
Ten ml (milliliter) of blood is usually needed for
each blood culture bottle. First a healthcare worker
locates a vein in the inner elbow region. The area of
skin where the blood will be drawn must be disinfected to prevent any microorganisms on a person’s
skin from entering the blood culture bottle and contaminating it. The area is disinfected by wiping the
area with alcohol in a circular fashion, starting with
tiny circles at the spot where the needle will puncture
the skin and enlarging the size of the circles while
wiping away from the puncture site. The same
pattern of wiping is repeated using an iodine or iodophor solution. The top of the bottle is disinfected
using alcohol. After the person’s skin has been
disinfected, the healthcare worker draws the blood
and about 10 ml of blood is injected into each
blood culture bottle. The type of bottles used will
vary based on whether the physician is looking
for bacteria (aerobes or anaerobes), yeast, mold, or
viruses.

consistent with a blood infection caused by the microorganism that was found. The microorganism is
usually found in more than one culture, it usually
grows soon after the bottles are incubated, and it is
often the cause of an infection somewhere else in the
person’s body.
When the culture is positive because of contamination, the patient’s clinical condition usually is not
consistent with an infection from the identified
microorganism. In addition, the microorganism is
often one commonly found on skin, it rarely causes
infection, it is found in only one bottle, and it may
appear after several days of incubation. More than
one microorganism often grow in contaminated
cultures.
Resources
ORGANIZATIONS

American Society of Microbiology. 1752 N Street N.W.,
Washington, D.C. 20036. (202) 737-3600. <http://
www.asmusa.org>.

Nancy J. Nordenson

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops reduces bruising. Warm packs relieve discomfort.

Normal results
Normal results will be negative. A single negative
culture does not rule out a blood infection. False
negatives can occur if the person was started on
antibiotics before the blood was drawn, if the
environment for growth was not right, the timing
was off, or for some unknown reason the microorganism just didn’t grow. Three negative cultures
may be enough to rule out bacteremia in the case of
endocarditis.

Abnormal results
The physician’s skill in interpreting the culture
results and assessing the person’s clinical condition is
essential in distinguishing a blood culture that is positive because of a true infection from a culture that is
positive because it became contaminated. In true
bacteremia, the patient’s clinical condition should be
584

I Blood donation and registry
Definition
Blood donation refers to the process of collecting,
testing, preparing, and storing blood and blood components. Donors are most commonly unpaid volunteers, but they may also be paid by commercial
enterprises. Blood registry refers to the collection and
sharing of data about donated blood and ineligible
donors.

Purpose
The purpose of the blood collection and distribution system is to help ensure an adequate supply of
blood for accident victims, people needing surgery,
and people suffering from certain diseases, as well as
for medical research.
Sometimes, donors give blood specifically to
benefit a particular person. People preparing for elective surgery may donate their own blood to be held
and then returned to them during surgery. This is
known as autologous blood donation. Directed
donor blood has been donated by someone known
GALE ENCYCLOPEDIA OF MEDICINE

Apheresis—Extraction of a specific component
from donated blood, with the remainder returned
to the donor.
Autologous donation—Blood donated for the
donor’s own use.
Granulocytes—White blood cells.
Plasma—The liquid part of blood.
Platelets—Tiny, disklike elements of plasma that
promote clotting.

to the intended recipient, such as a family member or
friend.
Each year, more than four million Americans
receive blood transfusions involving more than
26 million units of blood (one unit equals 450 milliliters, or about one pint), or an average of about
32,000 units per day. All of that blood must be
collected, tested, prepared, stored, and delivered
to the appropriate sites. Roughly eight million
people in the United States donate blood each year;
about half of the total amount needed is provided
by the 36 regional blood centers of the American
Red Cross.
Whole blood and the various blood components
have many uses. Red blood cells, which carry oxygen,
are used to treat anemia. Platelets, which play a role in
controlling bleeding, are commonly used in the treatment of leukemia and other cancers. Fresh frozen
plasma is also used to control bleeding in people deficient in certain clotting factors. Cryoprecipitated
AHF, made from fresh frozen plasma, contains a few
specific clotting factors.

Precautions
To ensure the safety of the blood supply, a multitiered process of donor screening and deferral is
employed. This involves donor education, taking a
detailed health history of each prospective donor, and
giving potential donors a simple physical examination
(which includes taking a few drops of blood to test for
anemia). At any point in the process, a potential donor
may be ‘‘deferred,’’ or judged ineligible to donate blood.
This deferral may be temporary or permanent, depending on the reason. Potential donors are also encouraged
to ‘‘self-defer,’’ or voluntarily decline to donate, rather
than put future blood recipients at risk.
GALE ENCYCLOPEDIA OF MEDICINE

All donated blood is extensively tested before
being used. The first step is determining the blood
type, which indicates who can receive the blood.
Receiving the wrong type of blood can cause
death. Blood is also screened for any antibodies that
could cause complications for recipients. In addition,
blood is tested to screen out donors infected with
the following diseases: Hepatitis B surface antigen
ADD, hepatitis B core antibody, hepatitis C
virus antibody, HIV-1 and HIV-2 antibody, HIV p24
antigen, HTLV-I and HTLV-II antibodies, and
syphilis. Nucleic Acid Amplification testing is also
performed, and other tests may be done if a doctor
requests them.
In order to detect the greatest possible number of
infections, these screening tests are extremely sensitive. For this reason, however, donors sometimes
receive false positive test results. In these cases,
more specific confirmatory tests are performed, to
help rule out false positive results. Blood found to
be abnormal is discarded, and all items coming into
direct contact with donors are used only once and
then discarded. Donors of infected blood are entered
into the Donor Deferral Register, a confidential
national data base used to prevent deferred people
from donating blood.
In general, blood donors must be at least 17 years
old (some states allow younger people to donate blood
with their parents’ consent), must weigh at least 110
pounds (50 kg), and must be in good health.
Many factors can temporarily or permanently
disqualify potential donors. Most of them have to
do with having engaged in behaviors that put them
at risk of infection or having spent time in certain
specified areas. Among these factors are having had a
tattoo, having had sex with people in high-risk
groups, having had certain diseases, and having
been raped.

Description
There are eight different blood types in all—four
ABO groups, each of which may be either Rh positive
or Rh negative. These types, and their approximate
distribution in the U.S. population, are as follows:
O+ (38%), O- (7%), A+ (34%), A- (6%), B+ (9%),
B- (2%), AB+ (3%), AB- (1%). In an emergency,
anyone can safely receive type O red blood cells,
and people with this blood type are known as
‘‘universal donors.’’ People with type AB blood,
known as ‘‘universal recipients,’’ can receive any type
of red blood cells and can give plasma to all blood
types.
585

Blood donation and registry

KEY TERMS

Blood donation and registry

Blood donations can be made in community
blood centers, at hospitals or in bloodmobiles, which
visit schools, churches and workplaces. The actual
process of donating whole blood takes about 20
minutes. A sterile needle is inserted into a vein in the
donor’s arm. The blood flows through plastic tubing
into a blood bag. Donors may be asked to clench their
fist to encourage blood to flow. Usually, one unit of
blood is collected. Afterward, donors are escorted to
an observation area, given light refreshments, and
allowed to rest.

screening tests, the transmission of infectious diseases via transfusion has been significantly diminished. Nonetheless, there is still a minuscule risk
that blood recipients could contract HIV, Hepatitis
C or other infections via transfusion. Other diseases
that could conceivably be contracted in this way, or
that are of particular concern to blood-collection
agencies, include babesiosis, Chagas disease, HTLVI and -II, Creutzfeldt-Jakob disease, cytomegalovirus, Lyme disease, malaria, and new variant
Creutzfeldt-Jakob disease.

Plasma, the liquid portion of the blood in which red
blood cells, platelets and other elements are suspended,
is also collected, often by commercial enterprises that
sell it to companies manufacturing clotting factors and
other blood products. This is done using a process
known as apheresis, in which whole blood is collected, the desired blood component is removed, and
the remainder is returned to the donor. Collecting
plasma generally takes one to two hours. Apheresis
may also be used to collect other blood components,
such as platelets and granulocytes.

Autologous blood donors run a tiny risk of having
the wrong blood returned to them due to clerical error.
There is also a faint possibility of bacterial contamination of the autologous blood.

Preparation
Once whole blood has been collected, it is sent to a
lab for testing and processing. Most donated blood is
separated into its constituent components, such as red
blood cells, platelets, and cryoprecipitate. This enables
more than one person to benefit from the same unit of
donated blood.
Different blood components vary in how long
they can be stored. Red blood cells can be refrigerated
for up to 42 days or frozen for as much as 10 years.
Platelets, stored at room temperature, may be kept for
up to five days. Fresh frozen plasma and cryoprecipitated AHF can be kept for as much as one year.

Aftercare
It generally takes about 24 hours for the donor’s
body to replenish the lost fluid. Replacing the lost red
blood cells, however, may take as much as two
months. Whole blood donors must wait a minimum
of eight weeks before donating again. Some states
place further limits on the frequency and/or total
number of times an individual may donate blood
within a 12-month period.

Risks
Thanks to the use of a multi-tiered screening
system and advances in the effectiveness of
586

Normal results
For most donors, the process is quick and painless
and they leave feeling fine. They may also find satisfaction in knowing that they have contributed to the
nation’s blood supply and may even have helped save
lives.

Abnormal results
Most blood donors suffer no significant aftereffects. Occasionally, however, donors feel faint or
dizzy, nauseous, and/or have pain, redness, or a bruise
where the blood was taken. More serious complications, which rarely occur, include fainting, muscle
spasms, and nerve damage.
Resources
PERIODICALS

McKenna, C. ‘‘Blood Minded’’ Nursing Times April 6, 2000:
27-28.
Wagner, H. ‘‘Umbilical Cord Blood Banking: Insurance
Against Future Diseases?’’ USA Today Magazine
(March 2000) : 59-61.
ORGANIZATIONS

American Association of Blood Banks. 8101 Glenbrook
Road, Bethesda, MD 20814-2749. (301) 907-6977.
<http://www.aabb.org>.
American Red Cross. 430 17th Street NW, Washington,
D.C. 20006. <http://www.redcross.org>.
National Blood Data Resource Center. (301) 215-6506.
<http://www.nbdrc.org>.

Peter Gregutt

Blood fluke infection see Schistosomiasis
GALE ENCYCLOPEDIA OF MEDICINE

Blood gas analysis

I Blood gas analysis
Definition
Blood gas analysis, also called arterial blood gas
(ABG) analysis, is a test which measures the amounts
of oxygen and carbon dioxide in the blood, as well as
the acidity (pH) of the blood.

Purpose
An ABG analysis evaluates how effectively the
lungs are delivering oxygen to the blood and how
efficiently they are eliminating carbon dioxide from
it. The test also indicates how well the lungs and
kidneys are interacting to maintain normal blood pH
(acid-base balance). Blood gas studies are usually
done to assess respiratory disease and other conditions
that may affect the lungs, and to manage patients
receiving oxygen therapy (respiratory therapy). In
addition, the acid-base component of the test provides
information on kidney function.

Description
Blood gas analysis is performed on blood from an
artery. It measures the partial pressures of oxygen and
carbon dioxide in the blood, as well as oxygen content,
oxygen saturation, bicarbonate content, and blood pH.
Oxygen in the lungs is carried to the tissues through
the bloodstream, but only a small amount of this oxygen can actually dissolve in arterial blood. How much
dissolves depends on the partial pressure of the oxygen
(the pressure that the gas exerts on the walls of the
arteries). Therefore, testing the partial pressure of oxygen is actually measuring how much oxygen the lungs
are delivering to the blood. Carbon dioxide is released
into the blood as a by-product of cell metabolism. The
partial carbon dioxide pressure indicates how well the
lungs are eliminating this carbon dioxide.
The remainder of oxygen that is not dissolved in
the blood combines with hemoglobin, a protein–iron
compound found in the red blood cells. The oxygen
content measurement in an ABG analysis indicates
how much oxygen is combined with the hemoglobin.
A related value is the oxygen saturation, which compares the amount of oxygen actually combined with
hemoglobin to the total amount of oxygen that the
hemoglobin is capable of combining with.
Carbon dioxide dissolves more readily in the blood
than oxygen does, primarily forming bicarbonate and
smaller amounts of carbonic acid. When present in
GALE ENCYCLOPEDIA OF MEDICINE

A blood gas analyzer from Corning Corporation. (Photograph by
Hank Morgan, Photo Researchers, Inc. Reproduced by permission.)

KEY TERMS
Acid-base balance—The condition that exists
when the body’s carbonic acid-bicarbonate buffer
system is in equilibrium, helping to maintain the
blood pH at a normal level of 7.35–7.45.
Hemoglobin—A protein—iron compound in red
blood cells that functions primarily in carrying
oxygen from the lungs to the tissues of the body.
pH—A measure of the acidity of a solution. Normal
blood pH ranges from 7.35–7.45.

normal amounts, the ratio of carbonic acid to bicarbonate creates an acid-base balance in the blood, helping to keep the pH at a level where the body’s cellular
functions are most efficient. The lungs and kidneys
587

Blood sugar tests

both participate in maintaining the carbonic acidbicarbonate balance. The lungs control the carbonic
acid level and the kidneys regulate the bicarbonate. If
either organ is not functioning properly, an acid-base
imbalance can result. Determination of bicarbonate
and pH levels, then, aids in diagnosing the cause of
abnormal blood gas values.
The procedure
The blood sample is obtained by arterial puncture
(usually in the wrist, although it could be in the groin
or arm) or from an arterial line already in place. If a
puncture is needed, the skin over the artery is cleaned
with an antiseptic. A technician then collects the blood
with a small sterile needle attached to a disposable
syringe. The patient may feel a brief throbbing or
cramping at the site of the puncture. After the blood
is drawn, the sample must be transported to the
laboratory as soon as possible for analysis.



oxygen content (O2CT): 15–23%



oxygen saturation (SaO2): 94–100%



bicarbonate (HCO3): 22–26 mEq/liter



pH: 7.35–7.45

Abnormal results
Values that differ from those listed above may
indicate respiratory, metabolic, or kidney disease.
These results also may be abnormal if the patient
has experienced trauma that may affect breathing
(especially head and neck injuries). Disorders, such
as anemia, that affect the oxygen-carrying capacity
of blood, can produce an abnormally low oxygen
content value.
Resources
BOOKS

Thompson, June, et al. Mosby’s Clinical Nursing. 4th ed.
St. Louis: Mosby, 1997.

Preparation
There are no special preparations. Patients have no
restrictions on drinking or eating before the test. If the
patient is receiving oxygen, the oxygen concentration
must remain the same for 20 minutes before the test; if
the test is to be taken without oxygen, the gas must be
turned off for 20 minutes before the test is taken. The
patient should breathe normally during the test.

Carol A. Turkington

Blood poisoning see Acute lymphangitis
Blood registry see Blood donation and
registry
Blood removal see Phlebotomy

Aftercare
After the blood has been taken, the technician
or the patient applies pressure to the puncture site
for 10–15 minutes to stop the bleeding, and then places
a dressing over the puncture.The patient should rest
quietly while applying the pressure to the puncture
site. Health care workers will observe the patient for
signs of bleeding or circulation problems

Risks
Risks are very low when the test is done correctly.
Risks include bleeding or bruising at the site, or delayed
bleeding from the site. Very rarely, there may be a
problem with circulation in the puncture area.

Normal results
Normal blood gas values are as follows:


partial pressure of oxygen (PaO2): 75–100 mm Hg



partial pressure of carbon dioxide (PaCO2): 35–45
mm Hg

588

I Blood sugar tests
Definition
Blood sugar tests include several different tests
that measure the amount of sugar (glucose) in a person’s blood. These tests are performed either on an
empty stomach, or after consuming a meal or premeasured glucose drink. Blood sugar tests are done
primarily to diagnose and evaluate a person with
diabetes mellitus.

Purpose
The body uses sugar, also called glucose, to supply
the energy it needs to function. People get sugar from
their diet and from their body tissues. Insulin is made
by the pancreas and affects the outer membrane of
cells, making it easy for glucose to move from the
blood into the cells. When insulin is active, blood
glucose levels fall. Sugar from body tissues is stored
GALE ENCYCLOPEDIA OF MEDICINE

After a meal, blood glucose levels rise sharply.
The pancreas responds by releasing enough insulin to
take care of all the newly added sugar found in the
body. The insulin moves the sugar out of the blood
and into the cells. Only then does the blood sugar start
to level off and begin to fall. A person with diabetes
mellitus either does not make enough insulin, or
makes insulin that does not work properly. The result
is blood sugar that remains high, a condition called
hyperglycemia.
Diabetes must be diagnosed as early as possible. If
left untreated, it can damage or cause failure of the
eyes, kidneys, nerves, heart, blood vessels, and other
body organs. Hypoglycemia, or low blood sugar, also
may be discovered through blood sugar testing.
Hypoglycemia is caused by various hormone disorders
and liver disease, as well as by too much insulin.

Description
There are a variety of ways to measure a person’s
blood sugar.
Whole blood glucose test
Whole blood glucose testing can be performed by
a person in his or her home, and kits are available for
this purpose. The person pricks his or her finger (a
finger stick) with a sterile sharp blade from the kit. A
single drop of blood is placed on a strip in a portable
instrument called a glucometer. The glucometer
quickly determines the blood sugar and shows the
results on a small screen in usually a few seconds.
New technologies for monitoring glucose levels
will help diabetics better control their glucose levels.
These tests are particularly important for children
and adolescents. In mid-2002, the U.S. Food and
Drug Administration (FDA) approved a new home
test for use by children and adolescents (it had
already been approved for adults) called the Cygnus
GlucoWatch biographer that helped better detect
hypoglycemia. Studies show that more frequent
checks are better; new monitors such as this allow
for simpler frequent testing. Continuous monitoring
was in development in early 2004, as a company
called TheraSense, Inc. received preapproval from
the FDA for clinical trials on its home continuous
glucose monitor. The monitor was designed to provide users with real-time glucose data, alarms for
hypoglycemia and hyperglycemia and to show trends
in their blood sugar levels.
GALE ENCYCLOPEDIA OF MEDICINE

Fasting plasma glucose test
The fasting plasma glucose test is done on an
empty stomach. For the eight hours before the test,
the person must fast (nothing to eat or drink, except
water). The person’s blood is drawn from a vein by a
health care worker. The blood sample is collected into
a tube containing an anticoagulant. Anticoagulants
stop the blood from clotting. In the laboratory, the
tube of blood spins at high speed within a machine
called a centrifuge. The blood cells sink to the bottom
and the liquid stays on the top. This straw-colored
liquid on the top is the plasma. To measure the
glucose, a person’s plasma is combined with other
substances. From the resulting reaction, the amount
of glucose in the plasma is determined.
Oral glucose tolerance test
The oral glucose tolerance test is conducted to see
how well the body handles a standard amount of
glucose. This test measures the amount of glucose in
a person’s plasma before and two hours after drinking
a large premeasured beverage containing glucose. The
person must eat a consistent diet, containing at least
5.25 oz (150g) of carbohydrates each day, for three
days before this test. For eight hours before the test,
the person must fast. A health care provider draws the
first sample of blood at the end of the fast to determine
the glucose level at the start of the test. The health care
provider then gives the person a beverage containing
2.6oz (75g) of glucose. Two hours later, the person’s
blood is drawn again. These blood samples are centrifuged and processed in the laboratory. A doctor can
then compare the before and after glucose levels to see
how well the patient’s body processed the sugar.
Two-hour postprandial blood glucose test
The two-hour postprandial blood glucose test measures the amount of glucose in plasma after a person eats
a specific meal containing a certain amount of sugar.
Although the meal follows a predetermined menu, it is
difficult to control many factors associated with this
testing method.
Blood sugar tests can be used in a variety of situations including:


Testing people suspected for diabetes. The American
Diabetic Association (ADA) recommends that either
a fasting plasma glucose test or an oral glucose tolerance test be used to diagnose diabetes. If the person
already has symptoms of diabetes, a blood glucose test
without fasting (called a casual plasma glucose test)
may be done. If the test result is abnormal, it must be
confirmed with another test performed on another
589

Blood sugar tests

in the form of glycogen. When glycogen is active,
blood glucose levels rise.

Blood sugar tests

day. The two tests can be different or they can be the
same, but they must be done on different days. If the
second test also is abnormal, the person has diabetes.
A two-hour postprandial test is not recommended by
the ADA as a test to use for the diagnosis of diabetes.
A doctor may order this test, and follow it with the
oral glucose tolerance test or the fasting plasma glucose test if the results are abnormal.






Testing pregnant women. Diabetes that occurs during pregnancy (gestational diabetes) is dangerous for
both the mother and the baby. Women who may be
at risk are screened when they are 24-28 weeks pregnant. A woman is considered at risk if she is older
than 25 years, is not at her normal body weight, has a
parent or sibling with diabetes, or if she is in an ethnic
group that has a high rate of diabetes (Hispanics,
Native Americans, Asians, African Americans).
The blood sugar test to screen for gestational diabetes is a variation of the oral glucose tolerance test.
Fasting is not required. If the result is abnormal,
a more complete test is done on another day.
Testing healthy people. Healthy people without
symptoms of diabetes should be screened for diabetes when they are 45 years old and again every
three years. Either the fasting plasma glucose or
oral glucose tolerance test is used for screening.
People in high risk groups should be tested before
the age of 45 and tested more frequently.
Testing of people already diagnosed with diabetes.
The ADA recommends that a person with diabetes
keep the amount of glucose in the blood at a normal
level as much as possible. This can be done by the
diabetic person testing his or her own blood at home
one or more times a day.

Preparation
Each blood sugar test that uses plasma requires a
5 mL blood sample. A healthcare worker ties a tight
band (tourniquet) on the person’s upper arm, locates a
vein in the inner elbow region, and inserts a needle into
the vein. Vacuum action draws the blood through the
needle into an attached tube. Collection of the sample
takes only a few minutes.
When fasting is required, the person should have
nothing to eat or drink (except water) for eight hours
before the test and until the test or series of tests is
completed. The person should not smoke before or
during the testing period because this can temporarily
increase the amount of glucose in the blood. Other
factors that can cause inaccurate results are a change
in diet before the test, illness or surgery two weeks
590

before the test, certain drugs, and extended bed rest.
The doctor may tell a person on insulin or taking pills
for diabetes to stop the medication until after the test.

Aftercare
After the test or series of tests is completed (and
with the approval of his or her doctor), the person
should eat, drink, and take any medications that
were stopped for the test.
The patient may feel discomfort when blood is
drawn from a vein. Bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops will reduce
bruising. Warm packs to the puncture site will relieve
discomfort.

Risks
If the person experiences weakness, fainting,
sweating, or any other unusual reaction while fasting
or during the test, he or she should immediately tell the
person giving the test.

Normal results
Normal results are:


fasting plasma glucose test less than 120 mg/dL



oral glucose tolerance test, 2 hours less than 140 mg/dL

For the diabetic person, the ADA recommends
an ongoing blood sugar goal of less than or equal to
120 mg/dL.

Abnormal results
These abnormal results indicate diabetes and
must be confirmed with repeat testing:


fasting plasma glucose test less than or equal to
126 mg/dL



oral glucose tolerance test, 2 hours less than or equal
to 200 mg/dL



casual plasma glucose test (nonfasting, with symptoms) less than or equal to 200 mg/dL



gestational oral glucose tolerance test, 1 hour less
than or equal to 140 mg/dL

Brain damage can occur from glucose levels below
40 mg/dL and coma from levels above 470 mg/dL.
A condition known as prediabetes or impaired
glucose tolerance, which may lead to Type 2 diabetes,
usually is indicated with a reading of 100 mg/dL. Other
hormone disorders can cause both hyperglycemia and
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

‘‘New Guidelines Set Lower Threshold for Precursor to
Diabetes.’’ RN (January 2004): 17.
Plotnick, Leslie P. ‘‘The Next Step in Blood Glucose
Monitoring?’’ Pediatrics (April 2003): 885.
‘‘Premarket Approval Application Filed for Continuous
Glucose Monitor.’’ Medical Letter on the CDC & FDA
(January 4, 2004): 26.
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
National Diabetes Information Clearinghouse.
1 Information Way, Bethesda, MD 20892-3560. (800)
860-8747. <http://www.niddk.nih.gov/health/diabetes/ndic.htm>.

Nancy J. Nordenson
Teresa G. Odle

Blood thinners see Anticoagulant and
antiplatelet drugs
Blood transfusion see Transfusion

typing and
I Blood
crossmatching
Definition
Blood typing is a laboratory test done to determine a person’s blood type. If the person needs a blood
transfusion, another test called crossmatching is done
after the blood is typed to find blood from a donor
that the person’s body will accept.

Purpose
Blood typing and crossmatching are most commonly done to make certain that a person who needs a
transfusion will receive blood that matches (is compatible with) his own. People must receive blood of the
same blood type, otherwise, a serious, even fatal,
transfusion reaction can occur.
GALE ENCYCLOPEDIA OF MEDICINE

Parents who are expecting a baby have their blood
typed to diagnose and prevent hemolytic disease of the
newborn (HDN), a type of anemia also known as
erythroblastosis fetalis. Babies who have a blood type
different from their mothers are at risk for developing
this disease. The disease is serious with certain blood
type differences, but is milder with others.
A child inherits factors or genes from each parent
that determine his blood type. This fact makes blood
typing useful in paternity testing. To determine
whether or not the alleged father could be the true
father, the blood types of the child, mother, and
alleged father are compared.
Legal investigations may require typing of blood
or other body fluids, such as semen or saliva, to identify persons involved in crimes or other legal matters.

Description
Blood typing and crossmatching tests are performed in a blood bank laboratory by technologists
trained in blood bank and transfusion services. The
tests are done on blood, after it has separated into cells
and serum (serum is the yellow liquid left after the
blood clots.) Costs for both tests are covered by insurance when the tests are determined to be medically
necessary.
Blood bank laboratories are usually located in
facilities, such as those operated by the American
Red Cross, that collect, process, and supply blood
that is donated, as well as in facilities, such as most
hospitals, that prepare blood for transfusion. These
laboratories are regulated by the United States Food
and Drug Administration (FDA) and are often
inspected and accredited by a professional association
such as the American Association of Blood Banks
(AABB).
Blood typing and crossmatching tests are based
on the reaction between antigens and antibodies. An
antigen can be anything that causes the body to launch
an attack, known as an immune response, against it.
The attack begins when the body builds a special
protein, called an antibody, that is uniquely designed
to attack and make ineffective (neutralize) the specific
antigen that caused the attack. A person’s body normally doesn’t make antibodies against its own antigens, only against antigens that are foreign to it.
A person’s body contains many antigens. The antigens found on the surface of red blood cells are important because they determine a person’s blood type.
When red blood cells having a certain blood type antigen are mixed with serum containing antibodies against
591

Blood typing and crossmatching

hypoglycemia. Abnormal results must be interpreted by
a doctor who is aware of the person’s medical condition
and medical history.

Blood typing and crossmatching

Frequency (%) Of ABO And Rh Blood Types In U.S. Population

Racial Group
Whites
Blacks

ABO Blood Type
O
45%
49%

A
40%
27%

that antigen, the antibodies attack and stick to the
antigen. In a test tube, this reaction is observed as the
formation of clumps of cells (clumping).
When blood is typed, a person’s cells and serum
are mixed in a test tube with commercially-prepared
serum and cells. Clumping tells which antigens or
antibodies are present and reveals the person’s blood
type. When blood is crossmatched, patient serum
is mixed with cells from donated blood that might be
used for transfusion. Clumping or lack of clumping
in the test tube tells whether or not the blood is
compatible.
Although there are over 600 known red blood cell
antigens, organized into 22 blood group systems, routine blood typing and crossmatching is usually concerned with only two systems: the ABO and Rh blood
group systems.
Blood typing
ABO BLOOD GROUP SYSTEM. In 1901, Karl
Landsteiner, an Austrian pathologist, randomly combined the serum and red blood cells of his colleagues.
From the reactions he observed in test tubes, he discovered the ABO blood group system. This discovery
earned him the 1930 Nobel Prize in Medicine.

A person’s ABO blood type–A, B, AB, or O–is
based on the presence or absence of the A and B
antigens on his red blood cells. The A blood type has
only the A antigen and the B blood type has only the
B antigen. The AB blood type has both A and B
antigens, and the O blood type has neither A nor B
antigen.
By the time a person is six months old, he naturally will have developed antibodies against the antigens his red blood cells lack. That is, a person with A
blood type will have anti-B antibodies, and a person
with B blood type will have anti-A antibodies. A person with AB blood type will have neither antibody, but
a person with O blood type will have both anti-A and
anti-B antibodies. Although the distribution of each of
the four ABO blood types varies between racial
592

B
11%
20%

AB
4%
4%

Rh Blood Type
Positive
85%
90%

Negative
15%
10%

groups, O is the most common and AB is the least
common.
ABO typing is the first test done on blood when it
is tested for transfusion. A person must receive ABOmatched blood. ABO incompatibilities are the major
cause of fatal transfusion reactions. ABO antigens are
also found on most body organs, so ABO compatibility is also important for organ transplants.
An ABO incompatibility between a pregnant
woman and her baby is a minor cause of HDN and
usually causes no problem for the baby. The structure
of ABO antibodies makes it unlikely they will cross the
placenta to attack the baby’s red blood cells.
Paternity testing compares the ABO blood types of
the child, mother, and alleged father. The alleged father
can’t be the true father if the child’s blood type requires
a gene that neither he nor the mother have. For example, a child with blood type B whose mother has blood
type O, requires a father with either AB or B blood type;
a man with blood type O cannot be the true father.
In some people, ABO antigens can be found in
body fluids other than blood, such as saliva and
semen. ABO typing of these fluids provides clues in
legal investigations.
RH BLOOD GROUP SYSTEM. The Rh, or Rhesus,
system was first detected in 1940 by Landsteiner and
Wiener when they injected blood from rhesus monkeys
into guinea pigs and rabbits. More than 50 antigens have
since been discovered belonging to this system, making
it the most complex red blood cell antigen system.

In routine blood typing and crossmatching tests,
only one of these 50 antigens, the D antigen, also
known as the Rh factor or Rho[D], is tested for.
If the D antigen is present, that person is Rh-positive;
if the D antigen is absent, that person is Rh-negative.
Other important antigens in the Rh system are C,
c, E, and e. These antigens are not usually tested for in
routine blood typing tests. However, testing for the
presence of these antigens is useful in paternity testing,
and when a technologist tries to identify unexpected
GALE ENCYCLOPEDIA OF MEDICINE

ABO
antigens

Blood typing and crossmatching

Recipient's blood

Reactions with donor's red blood cells

ABO
ABO blood Donor type Donor type Donor type Donor type
antibodies
type
O cells
A cells
B cells
AB cells

None

Anti-A
Anti-B

O

A

Anti-B

A

B

Anti-A

B

A&B

None

AB

I
I
I
I

Compatible

I I I
I I I
I I I

I I I
Not compatible

Blood typing is a laboratory test done to discover a person’s blood type. If the person needs a blood transfusion, crossmatching is done following blood typing to locate donor blood that the person’s body will accept. (Illustration by Electronic
Illustrators Group.)

Rh antibodies or find matching blood for a person
with antibodies to one or more of these antigens.
Unlike the ABO system, antibodies to Rh antigens don’t develop naturally. They develop only as an
immune response after a transfusion or during
pregnancy.
The incidence of the Rh blood types varies
between racial groups, but not as widely as the ABO
blood types: 85% of whites and 90% of blacks are
Rh-positive; 15% of whites and 10% of blacks are
Rh-negative.
In transfusions, the Rh system is next in importance after the ABO system. Most Rh-negative people
who receive Rh-positive blood will develop anti-D
antibodies. A later transfusion of Rh-positive blood
could result in a severe or fatal transfusion reaction.
Rh incompatibility is the most common and
severe cause of HDN. This incompatibility can
GALE ENCYCLOPEDIA OF MEDICINE

happen when an Rh-negative woman and an Rhpositive man produce an Rh-positive baby. Cells
from the baby can cross the placenta and enter the
mother’s bloodstream, causing the mother to make
anti-D antibodies. Unlike ABO antibodies, the structure of anti-D antibodies makes it likely that they will
cross the placenta and enter the baby’s bloodstream.
There, they can destroy the baby’s red blood cells,
causing severe or fatal anemia.
The first step in preventing HDN is to find out
the Rh types of the expectant parents. If the mother is
Rh-negative and the father is Rh-positive, the baby is
at risk for developing HDN. The next step is to test the
mother’s serum to make sure she doesn’t already have
anti-D antibodies from a previous pregnancy or transfusion. This procedure is similar to blood typing.
Finally, the Rh-negative mother is given an injection
of Rh Immunoglobulin (RhIg) at 28 weeks of gestation and again after delivery, if the baby is Rh positive.
593

Blood typing and crossmatching

KEY TERMS
ABO blood type—Blood type based on the presence or absence of the A and B antigens on the
red blood cells.
Antibody—A special protein made by the body as a
defense against foreign material that enters the
body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune
response.
Antigen—Anything that causes the body to launch
an immune response against that antigen through
the production of antibodies.
Blood bank—A laboratory that specializes in blood
typing, antibody identification, and transfusion
services.
Blood type—Blood categories based on the presence or absence of certain antigens on the red
blood cells.
Crossmatch—A laboratory test done to confirm
that blood from a donor and blood from the recipient are compatible.
Gene—A piece of DNA, located on a chromosome, that determines how traits such as blood
type are inherited and expressed.
Immune response—The body’s attack against an
antigen that it considers foreign to itself. The attack
begins with the production of antibodies against
the antigen.
Rh blood type—Blood type based on the presence
or absence of the D antigen on the red blood cells.
Transfusion—The therapeutic introduction of
blood or a blood component into a patient’s
bloodstream.

The RhIg attaches to any Rh-positive cells from the
baby in the mother’s bloodstream, preventing them
from triggering anti-D antibody production in the
mother. An Rh-negative woman should also receive
RhIg following a miscarriage, abortion, or ectopic
pregnancy.
OTHER BLOOD GROUP SYSTEMS. Several other
blood group systems may be involved in HDN and
transfusion reactions, although they are much less
frequent than ABO and Rh. They are the Duffy,
Kell, Kidd, MNS, and P systems. Tests for antigens
from these systems are not included in routine blood
typing, but they are commonly used in paternity
testing.

594

Like Rh antibodies, antibodies in these systems
do not develop naturally, but as an immune response
after transfusion or during pregnancy. An antibody
screening test is done before a crossmatch to check
for unexpected antibodies to antigens in these systems. A person’s serum is mixed in a test tube with
commercially-prepared cells containing antigens
from these systems. If clumping occurs, the antibody
is identified.
Crossmatching
Crossmatching is the final step in pretransfusion
testing. It is commonly referred to as compatibility
testing, or ‘‘Type and Cross.’’
Before blood from a donor and the recipient are
crossmatched, both are ABO and Rh typed. In addition, antibody screening is done to look for antibodies to certain Rh, Duffy, MNS, Kell, Kidd, and
P system antigens. If an antibody to one of these
antigens is found, only blood without that antigen
will be compatible in a crossmatch. This sequence
must be repeated before each transfusion a person
receives.
To begin the crossmatch, blood from a donor with
the same ABO and Rh type as the rcipient is selected.
In a test tube, serum from the patient is mixed with red
blood cells from the donor. If clumping occurs, the
blood is not compatible; if clumping does not occur,
the blood is compatible. If an unexpected antibody is
found in either the patient or the donor, the blood
bank does further testing to make sure the blood is
compatible.
In an emergency, when there is not enough time
for blood typing and crossmatching, O red blood cells
may be given, preferably Rh-negative. O blood type is
called the universal donor because it has no ABO
antigens for a patient’s antibodies to attack. In contrast, AB blood type is called the universal recipient
because it has no ABO antibodies to attack the antigens on transfused red blood cells. If there is time
for blood typing, red blood cells of the recipient type
(type specific cells) are given. In either case, the crossmatch is continued, even though the transfusion has
begun.

Preparation
To collect the 10 mL blood needed for these tests,
a healthcare worker ties a tourniquet above the
patient’s elbow, locates a vein in the inner elbow
region, and inserts a needle into that vein. Vacuum
GALE ENCYCLOPEDIA OF MEDICINE

Blood typing and crossmatching must be done
three days or less before a transfusion. A person
doesn’t need to change diet, medications, or activities
before these tests. He should tell his healthcare provider if, during the last three months, he has received a
blood transfusion or a plasma substitute, or has had a
radiology procedure using intravenous contrast
media. These can give false clumping reactions in
both typing and crossmatching tests.

Aftercare
The possible side effects of any blood collection
are discomfort or bruising at the site where the
needle punctured the skin, as well as dizziness or fainting. Bruising is reduced if pressure is applied with a
finger to the puncture site until the bleeding stops.
Discomfort is treated with warm packs to the
puncture site.

Risks
There are no risks from the blood collection or
test procedures. Blood transfusions always have the
risk of an unexpected transfusion reaction. A nurse
watches a patient for signs of a reaction during the
entire transfusion.

I Blood urea nitrogen test
Definition
The blood urea nitrogen (BUN) test measures the
level of urea nitrogen in a sample of the patient’s
blood. Urea is a substance that is formed in the liver
when the body breaks down protein. Urea then circulates in the blood in the form of urea nitrogen. In
healthy people, most urea nitrogen is filtered out by
the kidneys and leaves the body in the urine. If the
patient’s kidneys are not functioning properly or if the
body is using large amounts of protein, the BUN level
will rise. If the patient has severe liver disease, the BUN
will drop.

Purpose
The BUN level may be checked in order to assess
or monitor:


the presence or progression of kidney or liver disease.



blockage of urine flow.



mental confusion. Patients with kidney failure are
sometimes disoriented and confused.



abnormal loss of water from the body (dehydration).



recovery from severe burns. The body uses larger
than normal amounts of protein following serious
burns.

Description

Normal results
There is no normal blood type. The desired result
of a crossmatch is that compatible donor blood is
found. Compatibility testing procedures are designed
to provide the safest blood product possible for the
recipient, but a compatible crossmatch is no guarantee
that an unexpected adverse reaction will not appear
during the transfusion.

Abnormal results
Except in an emergency, a person cannot receive a
transfusion without a compatible crossmatch result.
Resources

The BUN test is performed on a sample of the
patient’s blood, withdrawn from a vein into a vacuum
tube. The procedure, which is called a venipuncture,
takes about five minutes.

Preparation
The doctor should check to make sure that the
patient is not taking any medications that can affect
BUN results. These drugs include the antibiotics chloramphenicol, streptomycin, amphotericin B, methicillin, gentamicin, tobramycin, and kanamycin, as well
as diuretics and corticosteroids.
The patient should be advised not to eat large
amounts of meat the day before the test.

ORGANIZATIONS

American Association of Blood Banks. 8101 Glenbrook
Road, Bethesda, MD 20814. (301) 907-6977. <http://
www.aabb.org>.

Nancy J. Nordenson
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
Aftercare consists of routine care of the area
around the venipuncture.
595

Blood urea nitrogen test

action draws the blood through the needle into an
attached tube. Collection of the sample takes only a
few minutes.

Body dysmorphic disorder

KEY TERMS
Urea—A compound containing nitrogen that
occurs in the urine and other body fluids as a result
of protein metabolism.

Risks
The primary risk is the possibility of a bruise or
swelling in the area of the venipuncture. The patient
can apply moist warm compresses.

Normal results
Normal BUN levels are 5-18 mg/dL for children;
7-18 mg/dL for adults; and 8-20 mg/dL in the elderly.

Abnormal results
BUN levels can be too low as well as too high.
Abnormally low BUN
Low levels of BUN may indicate overhydration,
malnutrition, celiac disease [a disease characterized by
the inability ot tolerate foods containing wheat protein (gluten)], liver damage or disease, or use of corticosteroids. Low BUN may also occur in early
pregnancy.

I Body dysmorphic disorder
Definition
Body dysmorphic disorder (BDD) is defined by
DSM-IV-TR as a condition marked by excessive preoccupation with an imaginary or minor defect in a
facial feature or localized part of the body. The diagnostic criteria specify that the condition must be sufficiently severe to cause a decline in the patient’s social,
occupational, or educational functioning. The most
common cause of this decline is the time lost
in obsessing about the ‘‘defect’’—one study found
that 68 percent of patients in a sample of adolescents
diagnosed with BDD spent three or more hours every
day thinking about the body part or facial feature of
concern. DSM-IV assigns BDD to the larger category
of somatoform disorders, which are disorders characterized by physical complaints that appear to be
medical in origin but that cannot be explained in
terms of a physical disease, the results of substance
abuse, or by another mental disorder.
The earliest known case of BDD in the medical
literature was reported by an Italian physician named
Enrique Morselli in 1886, but the disorder was not
defined as a formal diagnostic category until DSMIII-R in 1987. The World Health Organization
(WHO) did not add BDD to the International
Classification of Diseases (ICD) until 1992. The
word dysmorphic comes from two Greek words that
mean ‘‘bad’’ or ‘‘ugly’’ and ‘‘shape’’ or ‘‘form.’’ BDD
was previously known as dysmorphophobia.

Abnormally high BUN
High levels of BUN may indicate kidney disease or
failure; blockage of the urinary tract by a kidney stone
or tumor; a heart attack or congestive heart failure;
dehydration; fever; shock; or bleeding in the digestive
tract. High BUN levels can sometimes occur during
late pregnancy or result from eating large amounts of
protein-rich foods. A BUN level higher than 100 mg/
dL points to severe kidney damage.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Rebecca J. Frey, PhD

Blood vessel scan see Doppler
ultrasonography
596

Description
BDD is characterized by an unusual degree of
worry or concern about a specific part of the face or
body, rather than the general size or shape of the body.
It is distinguished from anorexia nervosa and bulimia
nervosa in that patients with eating disorders are
preoccupied with their overall weight and body
shape. As many as 50 percent of patients diagnosed
with BDD undergo plastic surgery to correct their
perceived physical defects.
Since the publication of DSM-IV in 1994, some
psychiatrists have suggested that there is a subtype of
BDD, namely muscle dysmorphia. Muscle dysmorphia is marked by excessive concern with one’s muscularity and/or fitness. Persons with muscle
dysmorphia spend unusual amounts of time working
out in gyms or exercising rather than dieting obsessively or seeking plastic surgery. DSM-IV-TR added
references to concern about body build and excessive
GALE ENCYCLOPEDIA OF MEDICINE

Body image—A term that refers to a person s inner
picture of his or her outward appearance. It has
two components: perceptions of the appearance
of one’s body, and emotional responses to those
perceptions.
Delusion—A false belief that is resistant to reason
or contrary to actual fact. Common delusions
include delusions of persecution, delusions about
one s importance (sometimes called delusions of
grandeur), or delusions of being controlled by
others. In BDD, the delusion is related to the
patient’s perception of his or her body.
Displacement—A psychological process in which
feelings originating from one source are expressed
outwardly in terms of concern or preoccupation
with an issue or problem that the patient considers
more acceptable. In some BDD patients, obsession
about the body includes displaced feelings, often
related to a history of childhood abuse.
Muscle dysmorphia—A subtype of BDD, described
as excessive preoccupation with muscularity and
body building to the point of interference with
social, educational, or occupational functioning.
Serotonin—A chemical produced by the brain that
functions as a neurotransmitter. Low serotonin
levels are associated with mood disorders, particularly depression. Medications known as selective
serotonin reuptake inhibitors (SSRIs) are used to
treat BDD and other disorders characterized by
depressed mood.
Somatoform disorders—A group of psychiatric disorders in the DSM-IV-TR classification that are
characterized by external physical symptoms or
complaints. BDD is classified as a somatoform
disorder.

weight lifting to DSM-IV’s description of BDD in
order to cover muscle dysmorphia.
BDD and muscle dysmorphia can both be
described as disorders resulting from the patient’s
distorted body image. Body image refers to a person’s mental picture of his or her outward appearance, including size, shape, and form. It has two
major components: how the person perceives their
physical appearance, and how they feel about their
body. Significant distortions in self-perception can
lead to intense dissatisfaction with one’s body and
dysfunctional behaviors aimed at improving one’s
GALE ENCYCLOPEDIA OF MEDICINE

appearance. Some patients with BDD are aware
that their concerns are excessive, but others do
not have this degree of insight; about 50 percent
of patients diagnosed with BDD also meet the
criteria for a delusional disorder.
The usual age of onset of BDD is late childhood or
early adolescence; the average age of patients diagnosed with the disorder is 17. BDD has a high rate of
comorbidity, which means that people diagnosed with
the disorder are highly likely to have been diagnosed
with another psychiatric disorder—most commonly
major depression, social phobia, or obsessive-compulsive disorder (OCD). About 29% of patients with
BDD eventually try to commit suicide.
BDD is thought to affect 1–2 percent of the general population in the United States and Canada,
although some doctors think that it is underdiagnosed
because it coexists so often with depression and other
disorders. In addition, patients are often ashamed of
grooming rituals and other behaviors associated with
BDD, and may avoid telling their doctor about them.
BDD is thought to affect men and women equally;
however, there are no reliable data as of the early
2000s regarding racial or ethnic differences in the incidence of the disorder.

Causes and symptoms
Causes
The causes of BDD fall into two major categories,
neurobiological and psychosocial.
NEUROBIOLOGICAL CAUSES. Research indicates
that patients diagnosed with BDD have serotonin
levels that are lower than normal. Serotonin is a neurotransmitter— a chemical produced by the brain that
helps to transmit nerve impulses across the junctions
between nerve cells. Low serotonin levels are associated with depression and other mood disorders.
PSYCHOSOCIAL CAUSES. Another important factor in the development of BDD is the influence of the
mass media in developed countries, particularly the
role of advertising in spreading images of physically
‘‘perfect’’ men and women. Impressionable children
and adolescents absorb the message that anything
short of physical perfection is unacceptable. They
may then develop distorted perceptions of their own
faces and bodies.

A young person’s family of origin also has a powerful influence on his or her vulnerability to BDD.
Children whose parents are themselves obsessed with
appearance, dieting, and/or body building, or who are
597

Body dysmorphic disorder

KEY TERMS

Body dysmorphic disorder

highly critical of their children’s looks, are at greater
risk of developing BDD.
An additional factor in some young people is a
history of childhood trauma or abuse. Buried feelings
about the abuse or traumatic incident may emerge
in the form of obsession about a part of the face or
body. This ‘‘reassignment’’ of emotions from the unacknowledged true cause to another issue is called displacement. For example, an adolescent who frequently
felt overwhelmed in childhood by physically abusive
parents may develop a preoccupation at the high
school level with muscular strength and power.
Symptoms
The central symptom of BDD is excessive concern
with a specific facial feature or body part. Research
indicates that the features most likely to be the focus of
the patient’s attention are (in order of frequency) complexion flaws (acne, blemishes, scars, wrinkles); hair
(on the head or the body, too much or too little); and
facial features (size, shape, or lack of symmetry). The
patient’s concerns may, however, involve other body
parts, and may shift over time from one feature to
another.
Other symptoms of body dysmorphic disorder
include:


Ritualistic behavior. Ritualistic behavior refers to
actions that the patient performs to manage anxiety
and that take up excessive amounts of his or her time.
Patients are typically upset if someone or something
interferes with or interrupts their ritual. Ritualistic
behaviors in BDD may include exercise or makeup
routines, assuming specific poses or postures in front
of a mirror, etc.



Camouflaging the ‘‘problem’’ feature or body part
with makeup, hats, or clothing. Camouflaging
appears to be the single most common symptom
among patients with BDD; it is reported by 94%.



Abnormal behavior around mirrors, car bumpers,
large windows, or similar reflecting surfaces. A
majority of patients diagnosed with BDD frequently
check their appearance in mirrors or spend long
periods of time doing so. A minority, however,
react in the opposite fashion and avoid mirrors
whenever possible.



Frequent requests for reassurance from others about
their appearance.



Frequently comparing one’s appearance to others.



Avoiding activities outside the home, including
school and social events.

598

Diagnosis
The diagnosis of BDD in children or adolescents
is often made by physicians in family practice because
they are more likely to have developed long-term relationships of trust with young people. At the adult
level, it is often specialists in dermatology, cosmetic
dentistry, or plastic surgery who may suspect that the
patient suffers from BDD because of frequent requests
for repeated or unnecessary procedures. Reported
rates of BDD among dermatology and cosmetic surgery patients range between 6 and 15 percent. The
diagnosis is made on the basis of the patient’s history
together with the physician’s observations of the
patient’s overall mood and conversation patterns.
People with BDD often come across to others as generally anxious and worried. In addition, the patient’s
dress or clothing styles may suggest a diagnosis of
BDD. It is not unusual, however, for patients with
BDD to take offense if their primary care doctor
suggests referral to a psychiatrist.
Some physicians may use a self-report questionnaire, such as the Multidimensional Body-Self
Relations Questionnaire (MBSRQ) or the short form
of the Situational Inventory of Body-Image Dysphoria
(SIBID), to evaluate patients during an office visit.
There are no brain imaging studies or laboratory
tests as of the early 2000s that can be used to diagnose
BDD.

Treatment
The standard course of treatment for body dysmorphic disorder is a combination of medications and
psychotherapy. Surgical, dental, or dermatologic
treatments have been found to be ineffective.
The medications most frequently prescribed for
patients with BDD are the selective serotonin reuptake
inhibitors, most commonly fluoxetine (Prozac) or sertraline (Zoloft). Other SSRIs that have been used with
this group of patients include fluvoxamine (Luvox)
and paroxetine (Paxil). In fact, it is the relatively high
rate of positive responses to SSRIs among BDD
patients that led to the hypothesis that the disorder
has a neurobiological component related to serotonin
levels in the body. An associated finding is that
patients with BDD require higher dosages of SSRI
medications than patients who are being treated for
depression with these drugs.
The most effective approach to psychotherapy
with BDD patients is cognitive-behavioral restructuring. Since the disorder is related to delusions about one’s
appearance, cognitive-oriented therapy that challenges
GALE ENCYCLOPEDIA OF MEDICINE

Some doctors recommend couples therapy or
family therapy in order to involve the patient s parents,
spouse, or partner in his or her treatment. This
approach may be particularly helpful if family members are critical of the patient s looks or are reinforcing
his or her unrealistic body image.

‘‘Body Dysmorphic Disorder,’’ Section 15, Chapter 186
inThe Merck Manual of Diagnosis and Therapy, edited
by Mark H. Beers, MD, and Robert Berkow, MD.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Johnston, Joni E., Psy D. Appearance Obsession: Learning to
Love the Way You Look. Deerfield Beach, FL: Health
Communications, Inc., 1994.
Rodin, Judith, PhD. Body Traps: Breaking the Binds That
Keep You from Feeling Good About Your Body. New
York: William Morrow, 1992.
PERIODICALS

Alternative treatment
Although no alternative or complementary
form of treatment has been recommended specifically for BDD, such herbal remedies for depression
as St. John’s wort have been reported as helping some
BDD patients. Aromatherapy appears to be a useful
aid to relaxation techniques as well as a pleasurable
physical experience for BDD patients. Yoga has
helped some persons with BDD acquire more realistic
perceptions of their bodies and to replace obsessions
about external appearance with new respect for their
body’s inner structure and functioning.

Prognosis
As of early 2005, the prognosis of BDD is considered good for patients receiving appropriate treatment. On the other hand, researchers do not know
enough about the lifetime course of body dysmorphic
disorder to offer detailed statistics. DSM-IV-TR notes
that the disorder ‘‘has a fairly continuous course, with
few symptom-free intervals, although the intensity of
symptoms may wax and wane over time.’’

Arthur, Gary K., MD, and Kim Monnell, DO. ‘‘Body
Dysmorphic Disorder.’’ eMedicine, 3 September 2004.
<http://www.emedicine.com/med/topic3124.htm>.
Cafri, G., J. K. Thompson, L. Ricciardelli, et al. ‘‘Pursuit of
the Muscular Ideal: Physical and Psychological
Consequences and Putative Risk Factors.’’ Clinical
Psychology Review 25 (February 2005): 215–239.
Kirchner, Jeffrey T. ‘‘Treatment of Patients with Body
Dysmorphic Disorder.’’ American Family Physician 61
(March 2000): 1837–1843.
Slaughter, James R. ‘‘In Pursuit of Perfection: A Primary
Care Physician’s Guide to Body Dysmorphic
Disorder.’’ American Family Physician 60 (October
1999): 569–580.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry.
3615 Wisconsin Avenue, NW, Washington, DC 200163007. (202) 966-7300. Fax: (202) 966-2891.
<www.aacap.org.>.
American Psychiatric Association (APA). 1000 Wilson
Boulevard, Suite 1825, Arlington, VA 22209-3901.
(800) 368-5777 or (703) 907-7322. Fax: (703) 907-1091.
<http://www.psych.org>.

Rebecca Frey, PhD

Prevention
Given the pervasive influence of the mass media in
contemporary Western societies, the best preventive
strategy involves challenging their unrealistic images
of attractive people. Parents, teachers, primary health
care professionals, and other adults who work with
young people can point out and discuss the pitfalls of
trying to look ‘‘perfect.’’ In addition, parents or other
adults can educate themselves about BDD and its
symptoms, and pay attention to any warning signs in
their children’s dress or behavior.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders, 4th edition, text revision.
Washington,DC: AmericanPsychiatric Association, 2000.
GALE ENCYCLOPEDIA OF MEDICINE

Body lice see Lice infestation

I Boils
Definition
Boils and carbuncles are bacterial infections of
hair follicles and surrounding skin that form pustules
(small blister-like swellings containing pus) around
the follicle. Boils are sometimes called furuncles. A
carbuncle is formed when several furuncles merge
to form a single deep abscess with several heads or
drainage points.
599

Boils

inaccurate self-perceptions is more effective than purely
supportive approaches. Thought-stopping and relaxation techniques also work well with BDD patients
when they are combined with cognitive restructuring.

Boils

Description
Boils and carbuncles are firm reddish swellings
about 0.2–0.4in (5-10 mm) across that are slightly raised
above the skin surface. They are sore to the touch. A
boil usually has a visible central core of pus; a carbuncle
is larger and has several visible heads. Boils occur most
commonly on the face, back of the neck, buttocks,
upper legs and groin area, armpits, and upper torso.
Carbuncles are less common than single boils; they are
most likely to form at the back of the neck. Males are
more likely to develop carbuncles.
Boils and carbuncles are common problems in the
general population, particularly among adolescents
and adults. People who are more likely to develop
these skin infections include those with:


diabetes, especially when treated by injected insulin



alcoholism or drug abuse



poor personal hygiene



crowded living arrangements



jobs or hobbies that expose them to greasy or oily
substances, especially petroleum products



allergies or immune system disorders, including HIV
infection.



family members with recurrent skin infections

Boils often occur from a bacterial infection in a hair follicle or
skin gland. (Custom Medical Stock Photo. Reproduced by
permission.)

Causes and symptoms
Boils and carbuncles are caused by Staphylococcus
aureus, a bacterium that causes an infection in an oil
gland or hair follicle. Although the surface of human
skin is usually resistant to bacterial infection, S. aureus
can enter through a break in the skin surface–including
breaks caused by needle punctures for insulin or drug
injections. Hair follicles that are blocked by greasy
creams, petroleum jelly, or similar products are
more vulnerable to infection. Bacterial skin infections
can be spread by shared cosmetics or washcloths, close
human contact, or by contact with pus from a boil or
carbuncle.
As the infection develops, an area of inflamed tissue gradually forms a pus-filled swelling or pimple that
is painful to touch. As the boil matures, it forms a
yellowish head or point. It may either continue to
swell until the point bursts open and allows the pus to
drain, or it may be gradually reabsorbed into the skin.
It takes between one and two weeks for a boil to heal
completely after it comes to a head and discharges
pus. The bacteria that cause the boil can spread into
other areas of the skin or even into the bloodstream
if the skin around the boil is injured by squeezing. If the
600

A close-up view of a carbuncle on person’s back. (Photograph
by John Watney, Photo Researchers, Inc. Reproduced by
permission.)

infection spreads, the patient will usually develop chills
and fever, swollen lymph nodes (lymphadenitis), and red
lines in the skin running outward from the boil.
Furunculosis is a word that is sometimes used
to refer to recurrent boils. Many patients have
repeated episodes of furunculosis that are difficult to
treat because their nasal passages carry colonies of
S. aureus. These bacterial colonies make it easy for
the patient’s skin to be reinfected. They are most likely
to develop in patients with diabetes, HIV infection, or
other immune system disorders.
Carbuncles are formed when the bacteria infect
several hair follicles that are close together.
Carbunculosis is a word that is sometimes used to
refer to the development of carbuncles. The abscesses
spread until they merge with each other to form a
single large area of infected skin with several pus-filled
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
The diagnosis of boils and carbuncles is usually
made by the patient’s primary care doctor on the basis
of visual examination of the skin. In some cases involving recurrent boils on the face, the doctor may need
to consider acne as a possible diagnosis, but for the
most part boils and carbuncles are not difficult to
distinguish from other skin disorders.

Treatment

Boils

heads. Patients with carbuncles may also have a lowgrade fever or feel generally unwell.

KEY TERMS
Abscess—A localized collection of pus in the skin
or other body tissue.
Carbuncle—A large, deep skin abscess formed by a
group or cluster of boils.
Follicle—The small sac at the base of a hair shaft.
The follicle lies below the skin surface.
Furunculosis—A condition in which the patient
suffers from recurrent episodes of boils.
Pustule—A small raised pimple or blister-like swelling of the skin that contains pus.

Patient and family education
Patient education is an important part of the
treatment of boils and carbuncles. Patients need to
be warned against picking at or squeezing boils
because of the danger of spreading the infection into
other parts of the skin or bloodstream. It is especially
important to avoid squeezing boils around the mouth
or nose because infections in these areas can be carried
to the brain. Patients should also be advised about
keeping the skin clean, washing their hands carefully
before and after touching the boil or carbuncle, avoiding the use of greasy cosmetics or creams, and keeping
their towels and washcloths separate from those of
other family members. Some doctors may recommend
an antiseptic soap or gel for washing the infected
areas.
If the patient has had several episodes of furunculosis, the doctor may examine family members or close
contacts to see if they are carriers of S. aureus. In many
cases they also need treatment for boils or carbuncles.
Skin infections and reinfections involving small
groups or clusters of people are being reported more
frequently in the United States.
Medications
Boils are usually treated with application of antibiotic creams–usually clindamycin or polymyxin–following
the application of hot compresses. The compresses help
the infection to come to a head and drain.
Carbuncles and furunculosis are usually treated
with oral antibiotics as well as antibiotic creams or
ointments. The specific medications that are given
are usually dicloxacillin (Dynapen) or cephalexin
(Keflex). Erythromycin may be given to patients who
are allergic to penicillin. The usual course of oral antibiotics is 5-10 days; however, patients with recurrent
furunculosis may be given oral antibiotics for longer
GALE ENCYCLOPEDIA OF MEDICINE

periods. Furunculosis is treated with a combination of
dicloxacillin and rifampin (Rifadin).
Patients with bacterial colonies in their nasal passages are often given mupirocin (Bactroban) to apply
directly to the lining of the nose.
Surgical treatment
Boils and carbuncles that are very large, or that
are not draining, may be opened with a sterile needle
or surgical knife to allow the pus to drain. The doctor
will usually give the patient a local anesthetic if a knife
is used; surgical treatment of boils is painful and
usually leaves noticeable scars.

Alternative treatment
Naturopathic therapy
Naturopathic practitioners usually recommend
changes in the patient’s diet as well as applying herbal
poultices to the infected area. The addition of zinc
supplements and vitamin A to the diet is reported to
be effective in treating boils. The application of a paste
or poultice containing goldenseal (Hydrastis canadensis) root is recommended by naturopaths on the
grounds that goldenseal helps to kill bacteria and
reduce inflammation.
Homeopathy
Homeopaths maintain that taking the proper
homeopathic medication in the first stages of a boil
or carbuncle will bring about early resolution of the
infection and prevent pus formation. The most likely
choices are Belladonna or Hepar sulphuris. If the boil
601

Bone biopsy

has already formed, Mercurius vivus or Silica may be
recommended to bring the pus to a head.

Definition

Western herbal therapies
A variety of herbal remedies can be applied topically
to boils to fight infection. These include essential oils
of bergamot (Citrus bergamia), chamomile (Matricaria
recutita), lavender (Lavandula officinalis), and sage
(Salvia officinalis), as well as tea tree oil (Melaleuca
spp.). Herbalists also recommend washing the skin
with a mixture of goldenseal and witch hazel. To
fight the inflammation associated with boils, herbalists
suggest marsh mallow (Althaea officinalis) ointment,
tinctures (herbal solutions made with alcohol) of blue
flag (Iris versicolor) or myrrh (Commiphora molmol), and
slippery elm (Ulmus fulva) made into a poultice.

Bone biopsy is the removal of a piece of bone
for laboratory examination and analysis.

Purpose
Bone biopsy is used to distinguish between malignant tumors and benign bone disease such as osteoporosis and osteomyelitis. This test may be ordered
to determine why a patient’s bones ache or feel sore,
or when a mass or deformity is found on an x ray,
CT scan, bone scan, or other diagnostic imaging
procedure.

Precautions

Prognosis
The prognosis for most boils is excellent. Some
patients, however, suffer from recurrent carbuncles or
furunculosis. In addition, although the spread of infection from boils is relatively unusual, there have been
deaths reported from brain infections caused by
squeezing boils on the upper lip or in the tissue folds
at the base of the nose.

Prevention

The patient’s doctor and the surgeon who performs the bone biopsy must be told about any prescription and over-the-counter medications the
patient is taking, and about allergies or reactions the
patient has had to anesthetics or pain relievers. Special
care must be taken with patients who have experienced
bleeding problems.

Description

There are some precautions that people can take
to minimize the risk of developing bacterial skin
infections:


cleanse skin properly with soap and water, and take
showers rather than tub baths



do not share washcloths, towels, or facial cosmetics
with others



cut down on greasy or fatty foods and snacks



always wash hands before touching the face



consider using antiseptic soaps and shower gels



consult a doctor if furunculosis is a persistent problem–it may indicate an underlying disease such as
diabetes

Resources
BOOKS

Hacker, Steven M. ‘‘Common Bacterial and Fungal
Infections of the Integument.’’ In Current Diagnosis,
edited by Rex B. Conn, et al. Vol 9. Philadelphia: W. B.
Saunders Co., 1997.

Rebecca J. Frey, PhD
602

I Bone biopsy

A bone biopsy involves using a special drill or
other surgical instruments to remove bone from the
patient’s body. The procedure usually lasts about 30
minutes and may be performed in the hospital, a doctor’s office, or a surgical center.
A drill biopsy is generally used to obtain a small
specimen. After the skin covering the bone has been
cleansed with an antiseptic and shaved, the patient
is given a local anesthetic. The doctor will not begin
the procedure until the anesthetic has numbed the
area from which the bone is to be removed, but the
patient may feel pressure or mild pain when
the needle pierces the bone. The surgeon turns the
needle in a half-circle to extract a sample from the
core, or innermost part, of the bone. The sample is
drawn into the hollow stem of the biopsy needle. The
sample is then sent to a laboratory, where it is examined under a microscope.
An open biopsy is used when a larger specimen is
needed. After the area covering the bone has been
cleansed with an antiseptic and shaved, the patient
is given a general anesthetic. After the anesthetic
takes effect and the patient is unconscious, the
GALE ENCYCLOPEDIA OF MEDICINE

Biopsy—Removal and examination of tissue to
determine if cancer is present.
Osteomyelitis—An infection of the bone that is
usually treated with antibiotics but sometimes
requires surgery.



some medications



mind-altering drugs

Normal results
Normal bone is made up of collagen fibers and
bone tissue.

Abnormal results

Osteoporosis—Thinning and loss of bone tissue.

Bone biopsy can reveal the presence of benign
disease, infection, or malignant tumors that have
spread to the bone from other parts of the body.
surgeon makes an incision and removes a bone specimen. The specimen is sent to the laboratory for
immediate analysis. Results of that analysis may
indicate that additional surgery should be performed
right away.

Preparation
No special preparation is needed for a drill biopsy,
but a patient must fast for at least 12 hours before an
open biopsy.

Aftercare
Pain medication will be prescribed after a biopsy,
and vital signs will be monitored until they return to
normal. Most patients can go home in about an hour.
If bone was removed from the spine, the patient may
stay in the hospital overnight. The surgical site must be
kept clean and dry for 48 hours, and the patient’s
doctor should be notified if any of these symptoms
appear:


fever



headache



pain on movement



inflammation or pus near the biopsy site



bleeding through the bandage at the biopsy site

Risks
Risks include bone fracture, injury to nearby
tissue, and infection. Bleeding is a rare complication.
Factors that increase risk include:


stress



obesity



poor nutrition



chronic illness

GALE ENCYCLOPEDIA OF MEDICINE

Results of this test are considered reliable, but
may be affected by:


failure to fast before open biopsy



failure to obtain an adequate specimen



delayed microscopic examination or laboratory
analysis

Resources
ORGANIZATIONS

Cancer Group Institute. 1814 N.E. Miami Gardens
Drive, North Miami Beach, FL 33179. (305)
651-5070. <http://www.cancergroup.com/
em19.html>.
National Institute of Arthritis and Musculoskeletal and Skin
Diseases Information Clearinghouse. National
Institutes of Health. 1 AMS Circle, Bethesda, MD
20892-3695. (301) 495-3675.

Maureen Haggerty

Bone break fever see Dengue fever
Bone cancer see Sarcomas
Bone densitometry see Bone density test

I Bone density test
Definition
A bone density test, or scan, is designed to check
for osteoporosis, a disease that occurs when the bones
become thin and weak. Osteoporosis happens when
the bones lose calcium and other minerals that keep
them strong. Osteoporosis begins after menopause in
many women, and worsens after age 65, often resulting in serious fractures. These fractures may not only
603

Bone density test

KEY TERMS

Bone density test

these tests are not as accurate as those that measure
density in the total body, spine or hip–where most
fractures occur.

Purpose

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A bone density scan measures the strength of an
individual’s bones and determines the risk of fracture.
An observation of any osteoporosis present can be
made.

Description
Computer read-out of a bone density scan. (Photo
Researchers. Reproduced by permission.)

rn

To take a DEXA bone density scan, the patient
lies on a bed underneath the scanner, a curving plastic
arm that emits x rays. These low-dose x rays form a
fan beam that rotates around the patient. During the
test, the scanner moves to capture images of the
patient’s spine, hip or entire body. A computer then
compares the patient’s bone strength and risk of
fracture to that of other people in the United States
at the same age and to young people at peak bone
density. Bones reach peak density at age 30 and then
start to lose mass. The test takes about 20 minutes to
do and is painless. The DEXA bone scan costs about
$250. Some insurance companies and Medicare cover
the cost. pDEXA wrist bone scans in drugstores are
available for about $30.

Preparation

Patient undergoing a bone density scan. (Photo Researchers.
Reproduced by permission.)

bring disability, but may affect longevity. As many as
one-fourth of women who fracture their hip after age
50 die within one year.
Most people today will get a bone density scan
from a machine using a technology called Dual Energy
X-ray Absorptiometry or DEXA for short. This
machine takes a picture of the bones in the spine,
hip, total body and wrist, and calculates their density.
If a DEXA machine is not available, bone density
scans can also be done with dual photon absorptiometry (measuring the spine, hip and total body) and
quantitative computed tomography scans (measuring
the spine). Bone density scanners that use DEXA technology to just measure bone density in the wrist (called
pDEXA scans) provide scans at some drugstores. Yet
604

The patient puts on a hospital gown and lies
on the bed underneath the scanner. Not all doctors
routinely schedule this test. If the following factors
apply to a patient, they may need a bone density
scan and can discuss this with their doctor. The
patient:


is at risk for osteoporosis



is near menopause



has broken a bone after a modest trauma



has a family history of osteoporosis



uses steroid or antiseizure medications



has had a period of restricted mobility for more than
six months

Risks
The DEXA bone scan exposes the patient to only
a small amount of radiation–about one-fiftieth that
of a chest x ray, or about the amount you get from
taking a cross-country airplane flight.
GALE ENCYCLOPEDIA OF MEDICINE

Calcium—A mineral that helps build bone. After
menopause, when women start making less of the
bone-protecting hormone estrogen, they may need
to increase their intake of calcium.
DEXA bone density scan—A bone density scan
that uses a rotating x-ray beam to measure the
strength of an individual’s bones and his or her
fracture risk.
Osteoporosis—A disease that occurs when the
bones lose the calcium and structure that keep
them strong. It often occurs after menopause
(around age 50) in women and in old age in men.

Resources
ORGANIZATIONS

National Osteoporosis Foundation. 1150 17th St., NW,
Suite 500, Washington, DC 20036-4603. (800) 2239994. <http://www.nof.org>.

Barbara Boughton

A bone densitometry scan of identical twins. Their bone
density is normal and identical to one another. (Photo
Researchers. Reproduced by permission.)

I Bone disorder drugs
Definition
Bone disorder drugs are medicines used to treat
diseases that weaken the bones.

Normal results
The patient, when compared with people at
‘‘young normal bone density’’ (called the T-score)
has the same or denser bones than a healthy 30-yearold. T scores above 1 mean that a patient has a healthy
bone mass. Scores from 0 to 1 mean that the patient
has borderline bone mass and should repeat the test in
two to five years.

Abnormal results
The patient has two to four times the risk of a
broken bone as other people in the United States at the
same age and those at peak bone density. If a patient’s T
score ranges from 1 to 2.5 they have low bone mass
and are at risk for osteoporosis. A T score below 2.5
means osteoporosis is already evident. These patients
should have a repeat bone density scan every year or two.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
The drugs described here are used to treat or prevent osteoporosis (brittle bone disease) in women past
menopause as well as older men. They also are used
prescribed for Paget’s disease, a painful condition that
weakens and deforms bones, and they are used to
control calcium levels in the blood.
Bone is living tissue. Like other tissue, bone is
constantly being broken down and replaced with new
material. Normally, there is a balance between the
breakdown of old bone and its replacement with new
bone. But when something goes wrong with the
process, bone disorders may result.
Osteoporosis is a particular concern for women
after menopause, as well as for older men. In osteoporosis, the inside of the bones become porous and
605

Bone disorder drugs

KEY TERMS

Bone disorder drugs

KEY TERMS
Estrogen—The main sex hormone that controls
normal sexual development in females. During
the menstrual cycle, estrogen helps prepare the
body for possible pregnancy.
Fracture—A break or crack in a bone.
Hormone—A substance that is produced in one
part of the body, then travels through the bloodstream to another part of the body where it has its
effect.
Menopause—The stage in a woman’s life when the
ovaries stop producing egg cells at regular times
and menstruation stops.
Osteoporosis—A disease in which bones become
very porous and weak. The bones are then more
likely to fracture and take longer to heal. The condition is most common in women after menopause
but can also occur in older men.

thin. Over time, this condition weakens the bones
and makes them more likely to break. Osteoporosis
is four times more common in women than in men.
This is because women have less bone mass than men,
tend to live longer and take in less calcium, and need
the female hormone estrogen to keep their bones
strong. If men live long enough, they are also at risk
of getting osteoporosis later in life. Once total bone
mass has peaked–around age 35–all adults start to lose
it. In women, the rate of bone loss speeds up during
menopause, when estrogen levels fall. Bone loss may
also occur if both ovaries are removed by surgery.
Ovaries make estrogen. Hormone replacement therapy
is one approach to preventing osteoporosis. However,
not all people can use hormone replacement therapy.
Bone disorder drugs are a good alternative for people
who already have osteoporosis or who are at risk
of developing it. Risk factors include lack of regular
exercise, early menopause, being underweight, and a
strong family history of osteoporosis.

Description
Bone disorder drugs are available only with a physician’s prescription and come in tablet, nasal spray, and
injectable forms. Commonly used bone disorder drugs
are alendronate (Fosamax), calcitonin (Miacalcin,
Calcimar), and raloxifene (Evista). Raloxifene belongs
to a group of drugs known as selective estrogen receptor modulators (SERMs), which act like estrogen in
some parts of the body but not in others. This makes
606

the drugs less likely to cause some of the harmful
effects that estrogen may cause. Unlike estrogen,
raloxifene does not increase the risk of breast cancer.
In fact, research suggests that raloxifene may even
reduce that risk.

Recommended dosage
Alendronate
FOR OSTEOPOROSIS. The usual dose is 10 mg once
a day. Treatment usually continues over many years.
FOR PAGET’S DISEASE. The usual dose is 40 mg

once a day for six months.
This medicine works only when it is taken with a
full glass of water first thing in the morning, at least 30
minutes before eating or drinking anything or taking
any other medicine. Do not lie down for at least 30
minutes after taking it because the drug can irritate the
esophagus, the tube that delivers food form the mouth
to the stomach.
Calcitonin
NASAL SPRAY. The usual dose is one spray into the
nose once a day. Alternate nostrils, spraying the right
nostril one day, the left nostril the next day, and so on.
INJECTABLE. The recommended dosage depends
on the condition for which the medicine is prescribed
and may be different for different people. Check with
the physician who prescribed the medicine or the
pharmacist who filled the prescription for the proper
dosage.

Raloxifene
The usual dose is one 60-mg tablet daily.

Precautions
Aldendronate
People with low levels of calcium in their blood
should not take this medicine. It also is not recommended for women on hormone replacement therapy
or for anyone with kidney problems. Before using
alendronate, anyone who has digestive or swallowing
problems should make sure that his or her physician
knows about the condition.
Calcitonin
Calcitonin nasal spray may cause irritation or
small sores in the nose. Check with a physician if this
GALE ENCYCLOPEDIA OF MEDICINE

The injectable form of calcitonin has caused serious allergic reactions in a few people. The nasal spray
is not known to cause such reactions, but the possibility exists. Before starting treatment with calcitonin,
the physician who prescribes the drug may order an
allergy test to make sure there will not be a problem.

Side effects
Aldendronate
Common side effects include constipation, diarrhea, indigestion, nausea, pain in the abdomen, and
pain in the muscles and bones. These problems usually
go away as the body adjusts to the medicine and do not
need medical attention unless they continue or they
interfere with normal activities.

Raloxifene
A rare, but serious side effect of raloxifene is an
increased risk of blood clots that form in the veins and
may break away and travel to the lungs. This is about
as likely in women who take raloxifene as it is in
women who take estrogen. Because of this possible
problem, women with a history of blood clots in
their veins should not take raloxifene.
Women who have had breast cancer or cancer of
the uterus should check with their physicians about
whether they can safely use raloxifene.
General precautions for bone disorder drugs
To keep bones strong, the body needs calcium and
vitamin D. Dairy products and fish such as salmon,
sardines and tuna are good sources of both calcium and
vitamin D. People who are taking bone disorder drugs
for osteoporosis and who do not get enough of these
nutrients in their diets should check with their physicians about taking supplements. Other important
bone-saving steps are avoiding smoking and alcohol
and getting enough of the kind of exercise that puts
weight on the bones (such as walking or lifting weights).
People who are taking these drugs because they
have too much calcium in their blood may need to
limit the amount of calcium in their diets. Too much
calcium may prevent the medicine from working properly. Discuss the proper diet with the physician who
prescribed the drug, and do not make any diet changes
without the physician’s approval.
Anyone who has had unusual reactions to bone
disorder drugs in the past should let his or her physician know before taking the drugs again. The physician also should be told about any allergies to foods,
dyes, preservatives, or other substances.
Women who are pregnant or who may become
pregnant and women who are breastfeeding should
check with their physicians before using this alendronate or calcitonin. Raloxifene should not be used by
women who are pregnant or who may become pregnant. In laboratory studies of rats, raloxifene caused
birth defects.
GALE ENCYCLOPEDIA OF MEDICINE

Calcitonin
The most common side effects of calcitonin nasal
spray are nose problems, such as dryness, redness,
itching, sores, bleeding and general discomfort. These
problems should go away as the body adjusts to the
medicine, but if they do not or if they are very uncomfortable, check with a physician. Other side effects that
should be brought to a physician’s attention include
headache, back pain and joint pain.
Injectable calcitonin may cause minor side effects
such as nausea or vomiting; diarrhea; stomach pain;
loss of appetite; flushing of the face, ears, hands or
feet; and discomfort or redness at the place on the
body where it is injected. Medical attention is not
necessary unless these problems persist or cause unusual
discomfort.
Anyone who has a skin rash or hives after taking
injectable calcitonin should check with a physician as
soon as possible.
Raloxifene
Common side effects include hot flashes, leg
cramps, nausea and vomiting. Women who have these
problems while taking raloxifene should check with
their physicians.

Interactions
Aldendronate
Taking aspirin with alendronate may increase the
chance of upset stomach, especially if the dose of
alendronate is more than 10 mg per day. If an analgesic is necessary, switch to another drug, such as acetaminophen (Tylenol) or use buffered aspirin. Ask a
physician or pharmacist for the correct medication
to use.
Some calcium supplements, antacids and other
medicines keep the body from absorbing alendronate.
To prevent this problem, do not take any other medicine within 30 minutes of taking alendronate.
607

Bone disorder drugs

becomes very uncomfortable or if there is bleeding
from the nose.

Bone grafting
Surgeons harvesting a sample of material for bone grafting. (Custom Medical Stock Photo, Inc. Reproduced by permission.)

Calcitonin
Calcitonin may keep certain other drugs for
Paget’s disease, such as etidronate (Didronel), from
working as they should.
Raloxifene
Raloxifene may affect blood clotting. Patients
who are taking other drugs that affect blood clotting,
such as warfarin (Coumadin), should check with their
physicians before using raloxifene.
Resources
ORGANIZATIONS

Foundation For Osteoporosis Research & Education. (888)
266-3015. <http://www.fore.org>.
National Association for the Relief of Paget’s Disease.
<http://www.demon.co.uk/narpd>.
National Osteoporosis Foundation 1150 17th Street NW
Suite 500 Washington, D.C. 20036-4603. <http://
www.nof.org>.

Nancy Ross-Flanigan
608

I Bone grafting
Definition
Bone grafting is a surgical procedure by which
new bone or a replacement material is placed into
spaces between or around broken bone (fractures) or
holes in bone (defects) to aid in healing.

Purpose
Bone grafting is used to repair bone fractures that
are extremely complex, pose a significant risk to the
patient, or fail to heal properly. Bone graft is also used
to help fusion between vertebrae, correct deformities,
or provide structural support for fractures of the
spine. In addition to fracture repair, bone graft is
used to repair defects in bone caused by birth defects,
traumatic injury, or surgery for bone cancer.

Description
Bone is composed of a matrix, mainly made up
of a protein called collagen. It is strengthened by
GALE ENCYCLOPEDIA OF MEDICINE

Allograft—Tissue for transplantation that is taken
from another person.
Autograft—Tissue for transplantation that is taken
from the patient.
Hydroxyapatite—A calcium phosphate complex
that is the primary mineral component of bone.
Osteoblasts—Bone cells that build new bone
tissue.
Osteoclasts—Bone cells that break down and
remove bone tissue.
Osteoconduction—Provision of a scaffold for the
growth of new bone.
Osteocytes—Bone cells that maintain bone tissue.
Osteogenesis—Growth of new bone.
Osteoinduction—Acceleration
formation by chemical means.

of

new

bone

deposits of calcium and phosphate salts, called
hydroxyapatite. Within and around this matrix are
located the cells of the bones, which are of four types.
Osteoblasts produce the bone matrix. Osteocytes
are mature osteoblasts and serve to maintain the
bone. Osteoclasts break down and remove bone tissue. Bone lining cells cover bone surfaces. Together,
these four types of cells are responsible for building
the bone matrix, maintaining it, and remodeling the
bone as needed.
There are three ways in which a bone graft can
help repair a defect. The first is called osteogenesis, the
formation of new bone by the cells contained within
the graft. The second is osteoinduction, a chemical
process in which molecules contained within the graft
(bone morphogenetic proteins) convert the patient’s
cells into cells that are capable of forming bone. The
third is osteoconduction, a physical effect by which the
matrix of the graft forms a scaffold on which cells in
the recipient are able to form new bone.
New bone for grafting can be obtained from other
bones in the patient’s own body (e.g., hip bones or
ribs), called autograft, or from bone taken from other
people that is frozen and stored in tissue banks, called
allograft. A variety of natural and synthetic replacement materials are also used instead of bone, including
collagen (the protein substance of the white fibers of
the skin, bone, and connective tissues); polymers, such
as silicone and some acrylics; hydroxyapatite; calcium
sulfate; and ceramics. A new material, called resorbable
GALE ENCYCLOPEDIA OF MEDICINE

polymeric grafts, is also being studied. These resorbable grafts provide a structure for new bone to grow
on; the grafts then slowly dissolve, leaving only the
new bone behind.
To place the graft, the surgeon makes an incision
in the skin over the bone defect and shapes the bone
graft or replacement material to fit into the defect.
After the graft is placed into the defect, it is held in
place with pins, plates, or screws. The incision is closed
with stitches and a splint or cast is used to prevent
movement of the bones while healing.
The costs associated with a bone graft vary. These
costs include: the surgeon’s fee (variable); anesthesiologist’s fees (averaging $350 to $400 per hour); hospital
charges (averaging $1,500 to $1,800 per day, more for
intensive care or private rooms); medication charges
($200 to $400); and additional charges, including an
assisting surgeon, treatment of complications, diagnostic procedures (e.g., blood work or x rays), medical
supplies, and equipment use. The cost for the graft
itself can range from $250 to $900.
This procedure is covered by many third-party
insurers; insurance coverage should be explored for
each individual case.

Aftercare
The time required for convalescence for fractures
or spinal fusion may vary from one to 10 days, and
vigorous exercise may be limited for up to three
months.
Most bone grafts are successful in helping the
bone defect to heal. The extent of recovery will depend
on the size of the defect and the condition of the bone
surrounding the graft at the time of surgery. Severe
defects may take some time to heal and may require
further attention after the initial graft. In one study of
over 1,000 patients who received very large allografts
after surgery for bone cancer, researchers found that
approximately 85% of the patients were able to return
to work or normal physical activities without using
crutches. However, about 25% of these patients
required a second operation, because the first did not
heal properly. Less severe bone defects, though,
should heal completely without serious complications.

Risks
The risks for any surgical procedure requiring
anesthesia include reactions to the medications and
breathing problems. The risks for any surgical procedure include bleeding and infection.
609

Bone grafting

KEY TERMS

Bone growth stimulation

The drawbacks of autografts include: the additional surgical and anesthesia time (typically 30 minutes per procedure) to obtain, or harvest, the bone for
grafting; added costs of the additional surgery; pain
and infection that might occur at the site from which
the graft is taken; and the relatively small amount of
bone that is available for grafting.
The drawbacks of allografts include: variability
between lots, since the bone is harvested from a variety
of donors; the bone may take longer to incorporate
with the host bone than an autograft would; the graft
may be less effective than an autograft; and the possibility of transferring diseases to the patient. Other
complications may result from the immune response
mounted by the patient’s immune system against the
grafted bone tissue. With the use anti-rejection agents
(drugs to combat rejection of grafted bone tissue)
immune rejection is less of a problem.

KEY TERMS
Anode—The positive electrode to which an electromagnetic current flows.
Cathode—The negative electrode from which an
electromagnetic current flows.

the application of low intensity ultrasound pulses as a
treatment for fracture nonunion.
Ultrasound and electromagnetic stimulation are
expensive and are used only when healing problems
exist for a substantial length of time. Each method
must be used for at least three to six months to be
effective.

Precautions

Resources

Bone growth stimulation cannot be used if the gap
between the ends of the fracture is too large.

ORGANIZATIONS

American Association of Tissue Banks. 1350 Beverly Road,
Suite 220-A, McLean, VA 22101. (703) 827-9582.

Lisa Christenson, PhD

I Bone growth stimulation

Description
Electric stimulation can be applied either from the
inside of the body (invasively) or from the outside the
body (noninvasively). Ultrasound is a noninvasive
procedure. The type of stimulation selected depends
on the doctor’s preference, the type and location of the
fracture, and the patient’s motivation to comply with
the treatment schedule. Treatment can take anywhere
from three to six months.

Definition
Bone growth stimulation is the technique of promoting bone growth in difficult to heal fractures by applying
a low electrical current or ultrasound to the fracture.

Purpose
Bone growth stimulation is done when satisfactory healing is not occurring naturally or when the
pace of healing is too slow. This condition is called
fracture nonunion, and it occurs more frequently
among adults than children, in people with severe or
complex fractures, and in people who smoke.
The theory behind applying an electric current to
fractures to stimulate healing is based on the fact that
the concave side of the bone becomes negatively
charged and the convex side is positively charged. It
is believed that artificially encouraging this charging
with an electric current will speed healing. In 1996, the
Food and Drug Administration (FDA) also approved
610

Invasive stimulators
Invasive electric stimulators are either fully or
partially implantable. The advantage of these devices
is that they apply a direct electric current to the fracture 24 hours a day. The fully implantable stimulator
requires little daily attention from the patient. Patients
using a semi-implanted stimulator must regulate their
own treatment schedule and have to care for the external power pack. The disadvantage of implantable and
semi-implantable stimulators is that their implantation is a surgical procedure.
Fully implantable direct current stimulators are
installed in a hospital under general or regional
anesthesia. Both the stimulator and the power source
are implanted. The surgeon makes an incision and
places a spiral shaped cathode inside the bone. A
wire leads to the power source and a small anode.
The power source is a battery pack that is implanted
in the nearby muscle. The body transmits electrical
GALE ENCYCLOPEDIA OF MEDICINE

Partially implanted stimulators use cathode pins
that are implanted at the edge of each bone that is
fractured. Wires lead to the surface of the skin where a
power source and the anode are located. Wires complete the circuit. The external portion of the device is
held in place by a cast. This source of stimulation also
runs continuously.
Noninvasive stimulators
In the noninvasive stimulator, external electromagnetic coils are placed on either side of the fracture
and are held in place by a strap or cuff. Locating the
coils correctly is important, and their location relative
to the fracture is usually confirmed by x rays.
The coils produce a pulsating electromagnetic
field. It is up to the patient to maintain the prescribed
treatment schedule. Effective treatment requires stimulation anywhere from three to ten hours each day
in periods of no less than one hour.
Ultrasound stimulation is the most recent treatment for stimulating bone growth. A device that generates low intensity pulses of sound is applied to the
skin over the fracture. The advantage of this technique
is that it is noninvasive and the period of application of
the sound pulses can be as short as 20-30 minutes each
day. The results of this treatment have been studied
less than the effect of electromagnetic stimulation.

unit works and caring for external devices and the
casts that hold them in place.

Risks
Noninvasive devices have few risks associated
with them. The main risk associated with implantable
devices is the development of infection at the site of
implantation.

Normal results
Success in healing a fracture nonunion using bone
growth stimulation depends on the type, location, and
severity of the fracture and the age and general health
of the patient.
Resources
PERIODICALS

Mayo Clinic. ‘‘Fractures - Treatment Methods are Tailored
to the Break.’’ Mayo Clinic Health Letter 14, no. 4
(April 1996): 1-3.

Tish Davidson, A.M.

Bone infection see Osteomyelitis

marrow aspiration and
I Bone
biopsy
Definition

Preparation
Bone growth stimulation is done only when healing has failed to occur for many months. Before it is
started, x rays are done of the fracture area. If the
device is to be implanted, standard preoperative
blood and urine tests are done. The patient may meet
with an anesthesiologist to discuss any conditions that
might affect the administration of anesthesia.

Aftercare
If a noninvasive, pulsating, electromagnetic field
device is used, the patient must not put any stress or
weight on the fracture until it is healed, which is a
matter of months in most cases. In all lower limb
fractures, regardless of the stimulation method used,
the patient can not bear weight on the limb with the
fracture until healing is complete. This limits the
patient’s mobility for many months. Patients have
the responsibility for regularly making sure that the
GALE ENCYCLOPEDIA OF MEDICINE

Bone marrow aspiration, also called bone marrow
sampling, is the removal by suction of fluid from the
soft, spongy material that lines the inside of most
bones. Bone marrow biopsy, or needle biopsy, is the
removal of a small piece of bone marrow.

Purpose
Bone marrow aspiration is used to:


pinpoint the cause of abnormal blood test results



confirm a diagnosis or check the status of severe
anemia (abnormally low numbers of red blood cells
in the bloodstream) of unknown cause, or other
irregularities in the way blood cells are produced or
become mature.



evaluate abnormalities in the blood’s ability to store
iron.



diagnose infection
611

Bone marrow aspiration and biopsy

current to close the circuit. The incision is then closed.
Once in place, the device provides continuous direct
electric current for bone growth stimulation.

Bone marrow aspiration and biopsy

Aspiration needle

Cortex

Inner spongy layer

Bone marrow

In a bone marrow aspiration, a needle is inserted beneath the skin and rotated until it penetrates the cortex, or outer covering of
the bone. A small amount of marrow is suctioned out of the bone by a syringe attached to the needle. (Illustration by Electronic
Illustrators Group.)

Bone marrow biopsy is used to:


obtain intact bone marrow for laboratory analysis



diagnose and stage some types of cancer or anemia
and other blood disorders



identify the source of an unexplained fever



diagnose fibrosis of bone marrow or myeloma (a
tumor composed of cells normally found in the
bone marrow) when bone marrow aspiration has
failed to provide an appropriate specimen

Bone marrow aspiration and bone marrow biopsy
are also used to gauge the effectiveness of chemotherapy and other medical treatments. These procedures
are often used together to ensure the availability of the
best possible bone marrow specimen.

Precautions
Allergies or previous adverse reactions to medications should be discussed with the doctor. Any current
medications, including herbal or nutritional supplements, should be evaluated for the potential to interfere
with proper coagulation (clot formation). These would
include coumadin, aspirin, and other agents used as
612

KEY TERMS
Aspiration—A procedure to withdraw fluid from
the body.
Connective tissue—Material that links one part of
the body with another.
Fibrosis—A condition characterized by the presence of scar tissue or fiber-containing tissues that
replace normal tissues.
Hematologist—A medical specialist who treats diseases and disorders of the blood and blood-forming
organs.
Hematoma—Blood that collects under the skin and
causes swelling.
Hemorrhage—Heavy bleeding.
Myeloma—A tumor that originates in bone marrow
and usually spreads to more than one bone.
Nurse practitioner—A registered nurse who is qualified to perform some specialized duties.
blood thinners. Caution should be used when the
herbs gingko, ginger, garlic, br ginseng have been utilized as supplements, due to a risk of bleeding.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Bone marrow aspiration and biopsy should be
performed by a physician or nurse clinician. Each
procedure takes about 20 to 30 minutes and is usually
performed on an outpatient basis, but can be done in a
hospital if necessary.
The skin covering the biopsy site is cleansed with
an antiseptic, and the patient may be given a mild
sedative. A local anesthetic is administered. The
hematologist or nurse clinician performing the procedure will not begin until the anesthetic has numbed
the area from which the specimen is to be extracted.
In both adults and children, aspiration and biopsy
are most commonly performed on the rear bone of
the hip (posterior iliac crest). In adults, sampling
from the sternum (breastbone) is sometimes done.
The latter location is technically easier, but is
somewhat more painful for the patient and presents
the risk of heart injury. On rare occasions, a long
bone of the leg (tibia) may be used as a sample site
for an infant.
In a bone marrow aspiration, a special needle is
inserted beneath the skin and rotated until it penetrates the cortex, or outer covering of the bone. At
least half a teaspoon of marrow is withdrawn from
the bone by a syringe attached to the needle. The
patient may experience discomfort when the needle
is inserted or when the marrow is aspirated. If more
marrow is needed, the needle is repositioned slightly,
a new syringe is attached, and a second sample is
taken. The samples are transferred from the syringes
to slides and vials, then sent to a laboratory for
analysis.
Bone marrow biopsy may be performed immediately before or after bone marrow aspiration. The
procedure utilizes a special large-bore needle that is
used to drill out a core of marrow. In bone marrow
biopsy, the needle is inserted, rotated from side to side,
withdrawn, and reinserted at a different angle. This
procedure is repeated if needed until a small core,
about 0.4 inches (1 cm) long, is separated from the
bone marrow. The needle is again removed, and a
piece of fine wire threaded through its tip transfers
the specimen onto sterile gauze. The patient may feel
discomfort or pressure when the needle is inserted and
experience a brief, pulling sensation when the marrow
is withdrawn. Unlike aspiration specimens, which are
GALE ENCYCLOPEDIA OF MEDICINE

smeared, these samples contain structurally intact
bone marrow. Microscopic examination can show
what material its cells contain and how they are alike
or different from one another. The bone may either be
embedded intact in paraffin (a type of wax), or be
decalcified (a process which takes place overnight)
for a different type of staining and examination.
Each type of preparation has certain advantages.

Preparation
A current history and physical are obtained from
the patient, along with proper consent. The patient is
generally placed in a prone position (lying face down)
for preparation, and local anesthetic, with or without
sedation, is administered.

Aftercare
After the needle is removed, the biopsy site will be
covered with a clean, dry bandage. Pressure is applied
to control bleeding. The patient’s pulse, breathing,
blood pressure, and temperature are monitored until
they return to normal, and the patient may be
instructed to remain in a supine position (lying face
up) for half an hour before getting dressed.
The patient should be able to leave the clinic and
resume normal activities immediately. Patients who
have received a sedative often feel sleepy for the rest
of the day; driving, cooking, and other activities that
require clear thinking and quick reactions should
therefore be avoided.
The biopsy site should be kept covered and dry
for several hours. Walking or taking prescribed pain
medications usually ease any discomfort felt at the
biopsy site, and ice can be used to reduce swelling.
A doctor should be notified if the patient:


feels severe pain more than 24 hours after the procedure.



experiences persistent bleeding or notices more than
a few drops of blood on the wound dressing.



has a temperature above 101  F (38.3  C). Inflammation and pus at the biopsy site and other signs
of infection should also be reported to a doctor without delay.

Risks
Bleeding and discomfort often occur at the biopsy
site. Infection and hematoma may also develop. In
rare instances, the heart or a major blood vessel is
pierced when marrow is extracted from the sternum
613

Bone marrow aspiration and biopsy

Pregnancy, lactation (production and secretion of
milk), and preexisting platelet or bleeding disorders
should be evaluated before either procedure is
undertaken.

Bone marrow transplantation

during bone marrow biopsy. This can lead to severe
hemorrhage.

- f'\ ~

Normal results
Healthy adult bone marrow contains yellow fat cells,
connective tissue, and red marrow that produces blood.
The bone marrow of a healthy infant is primarily red due
to active production of red cells necessary for growth.

Abnormal results
Culture of bone marrow aspirate may yield information about an infectious agent. Microscopic examination of bone marrow can reveal granulomas,
myelofibrosis, lymphomas, leukemias, or other cancers.
Analyzing specimens can help doctors diagnose iron
deficiency, vitamin B12 deficiency, and folate deficiency, as well as anemia.
Obesity can affect the ease with which a bone
marrow biopsy can be done, and the results of either
procedure can be affected if the patient has had
radiation therapy at the biopsy site.
Maureen Haggerty

I Bone marrow transplantation
Definition
The bone marrow—the sponge-like tissue found
in the center of certain bones—contains stem cells that
are the precursors of white blood cells, red blood cells,
and platelets. These blood cells are vital for normal
body functions, such as oxygen transport, defense
against infection and disease, and clotting. Blood
cells have a limited lifespan and are constantly being
replaced; therefore, healthy stem cells are vital.
In association with certain diseases, stem cells
may produce too many, too few, or otherwise abnormal blood cells. Also, medical treatments may
destroy stem cells or alter blood cell production.
The resultant blood cell abnormalities can be life
threatening.
Bone marrow transplantation involves extracting
bone marrow containing normal stem cells from a
healthy donor, and transferring it to a recipient
whose body cannot manufacture proper quantities of
normal blood cells. The goal of the transplant is to
rebuild the recipient’s blood cells and immune system
and hopefully cure the underlying ailment.
614

~ -,,et\
IL

In autologous bone marrow transplantation, stem cells are
collected from the patient. Once the patient has undergone
chemotherapy, the cells are replaced in the blood via an
intravenous catheter. The cells return to the bone marrow
and begin producing healthy new cells. (Illustration by
Argosy Inc.)

Purpose
A person’s red blood cells, white blood cells, and
platelets may be destroyed or may be abnormal due to
disease. Also, certain medical therapies, particularly
chemotherapy or radiation treatment, may destroy a
person’s stem cells. The consequence to a person’s
health is severe. Under normal circumstances, red
blood cells carry oxygen throughout the body and
remove carbon dioxide from the body’s tissues.
White blood cells form the cornerstone of the body’s
immune system and defend it against infection.
Platelets limit bleeding by enabling the blood to clot
if a blood vessel is damaged.
A bone marrow transplant is used to rebuild the
body’s capacity to produce these blood cells and bring
their numbers to normal levels. Illnesses that may be
treated with a bone marrow transplant include both
cancerous and noncancerous diseases.
Cancerous diseases may or may not specifically
involve blood cells; but, cancer treatment can destroy
the body’s ability to manufacture new blood cells. Bone
marrow transplantation may be used in conjunction
with additional treatments, such as chemotherapy, for
GALE ENCYCLOPEDIA OF MEDICINE

ABO antigen—Protein molecules located on the surfaces of red blood cells that determine a person’s
blood type: A, B, or O.
AML—Acute myelogenous leukemia, also called
acute myelocytic leukemia. Malignant disorder
where myeloid blast cells accumulate in the marrow
and bloodstream.
Allogeneic—Referring to bone marrow transplants
between two different, genetically dissimilar people.
Anemia—Decreased red cell production which
results in deficiency in oxygen-carrying capacity of
the blood.
Antigen—A molecule that is capable of provoking an
immune response.
Aplastic anemia—A disorder in which the body produces inadequate amounts of red blood cells and
hemoglobin due to underdeveloped or missing
bone marrow.
Autologous—Referring to bone marrow transplants
in which recipients serve as their own donors.
Blank—If an individual has inherited same HLA antigen from both parents, the HLA typing is designated
by the shared HLA antigen followed by a ‘‘blank’’(–).

Conditioning—Process of preparing patient to
receive marrow donation, often through the use of
chemotherapy and radiation therapy.
Confirmatory typing—Repeat tissue typing to confirm the compatibility of the donor and patient before
transplant.
Donor—A healthy person who contributes bone
marrow for transplantation.
Graft versus host disease—A life-threatening complication of bone marrow transplants in which the
donated marrow causes an immune reaction against
the recipient’s body.
Histocompatibility—The major histocompatibility
determinants are the human leukocyte antigens
(HLA) and characterize how well the patient and
donor are matched.
HLA (human leuckocyte antigen)—A group of protein molecules located on bone marrow cells that can
provoke an immune response. A donor’s and a recipient’s HLA types should match as closely as possible to
prevent the recipient’s immune system from attacking
the donor’s marrow as a foreign material that does not
belong in the body.

Blast cells—Blood cells in early stage of cellular
development.
Blast crisis—Stage of chronic myelogenous leukemia
where large quantities of immature cells are produced by the marrow and is not responsive to
treatment.
Bone marrow—A spongy tissue located within flat
bones, including the hip and breast bones and the
skull. This tissue contains stem cells, the precursors of
platelets, red blood cells, and white blood cells.

Hodgkin’s disease—A type of cancer involving the
lymph nodes and potentially affecting nonlymphatic
organs in the later stage.

Bone marrow transplant—Healthy marrow is
infused into people who have had high-dose chemotherapy for one of the many forms of leukemias,
immunodeficiencies, lymphomas, anemias, metabolic disorders, and sometimes solid tumors.

Lymphoma—A type of cancer that affects lymph
cells and tissues, including certain white blood cells
(T cells and B cells), lymph nodes, bone marrow, and
the spleen. Abnormal cells (lymphocyte/leukocyte)
multiply uncontrollably.

Chemotherapy—Medical treatment of a disease, particularly cancer, with drugs or other chemicals.
Chronic myelogenous leukemia (CML)—Also called
chronic myelocytic leukemia, malignant disorder
that involves abnormal accumulation of white cells
in the marrow and bloodstream.
Cytomegalovirus (CMV)—Virus that can cause
pneumonia in post bone marrow transplant patients.

Match—How similar the HLA typing, out of a possible six antigens, is between the donor and the
recipient.

GALE ENCYCLOPEDIA OF MEDICINE

Immunodeficiency—A disorder in which the
immune system is ineffective or disabled either due
to acquired or inherited disease.
Leukemia—A type of cancer that affects leukocytes, a
particular type of white blood cell. A characteristic
symptom is excessive production of immature or
otherwise abnormal leukocytes.

Mixed lymphocyte culture (MLC)—Test that measures level of reactivity between donor and recipient
lymphocytes.
Neuroblastoma—Solid tumor in children, may be
treated by BMT.

615

Bone marrow transplantation

KEY TERMS

Bone marrow transplantation

Platelets—Fragments of a large precursor cell, a
megakaryocyte found in the bone marrow. These
fragments adhere to areas of blood vessel damage
and release chemical signals that direct the formation
of a blood clot.
Recipient—The person who receives the donated
blood marrow.
Red blood cells—Cells that carry hemoglobin (the
molecule that transports oxygen) and help remove
wastes from tissues throughout the body.
Sickle cell anemia—An inherited disorder characterized by a genetic flaw in hemoglobin production.
(Hemoglobin is the substance within red blood cells
that enables them to transport oxygen.) The hemoglobin that is produced has a kink in its structure that

various types of leukemia, Hodgkin’s disease, lymphoma, breast and ovarian cancer, and other cancers.
Noncancerous diseases for which bone marrow transplantation can be a treatment option include aplastic
anemia, sickle cell anemia, thalassemia, and severe
immunodeficiency.

Precautions
Bone marrow transplants are not for everyone.
Transplants are accompanied by a risk of infection,
transplant rejection by the recipient’s immune system,
and other complications. The procedure has a lower
success rate the greater the recipient’s age. Complications are exacerbated for people whose health is
already seriously impaired as in late-stage cancers.
Therefore, a person’s age or state of health may
prohibit use of a bone marrow transplant. The typical
cut-off age for a transplant ranges from 40 to 55 years;
however, a person’s general health is usually the more
important factor.
Even in the absence of complications, the transplant and associated treatments are hard on the
recipient. Bone marrow transplants are debilitating. A
person’s ability to withstand the rigors of the transplant
is a key consideration in deciding to use this treatment.

Description
Autologous and allogeneic transplants
Two important requirements for a bone marrow
transplant are the donor and the recipient. Sometimes,
the donor and the recipient may be the same person.
This type of transplant is called an autologous
616

forces the red blood cells to take on a sickle shape,
inhibiting their circulation and causing pain. This
disorder primarily affects people of African descent.
Syngeneic—Referring to a bone marrow transplant
from one identical twin to the other.
Thalassemia—A group of inherited disorders that
affects hemoglobin production. (Hemoglobin is the
substance within red blood cells that enables them to
transport oxygen.) Because hemoglobin production is
impaired, a person with this disorder may suffer mild
to severe anemia. Certain types of thalassemia can be
fatal.
White blood cells—A group of several cell types that
occur in the bloodstream and are essential for a properly functioning immune system.

transplant. It is typically used in cases in which a
person’s bone marrow is generally healthy but will be
destroyed due to medical treatment for diseases such
as breast cancer and Hodgkin’s disease. Most bone
marrow transplants are autologous. If a person’s
bone marrow is unsuitable for an autologous transplant, the bone marrow must be derived from another
person in an allogeneic transplant.
Allogeneic transplants are more complicated
because of proteins called human lymphocyte antigens
(HLA) that are on the surface of bone marrow cells. If
the donor and the recipient have very dissimilar antigens, the recipient’s immune system regards the
donor’s bone marrow cells as invaders and launches
a destructive attack against them. Such an attack
negates any benefits offered by the transplant.
HLA matching
There are only five major HLA classes or types—
designated HLA–A,–B, –C,–D, and class III—but
much variation within the groupings. For example,
HLA–A from one individual may be similar to, but
not the same as, HLA–A in another individual; such a
situation can render a transplant from one to the other
impossible.
HLA matching is more likely if the donor and
recipient are related, particularly if they are siblings;
however, an unrelated donor may be a potential
match. Only in rare cases is matching HLA types
between two people not an issue: if the recipient has an
identical twin. Identical twins carry the same genes;
therefore, the same antigens. A bone marrow transplant
between identical twins is called a syngeneic transplant.
GALE ENCYCLOPEDIA OF MEDICINE

A relatively recent development in stem cell
transplantation is the use of peripheral blood cells
instead of stem cells from bone marrow. Peripheral
blood stem cells (PBSCs) are obtained from circulating blood rather than from bone marrow, but
the amount of stem cells found in the peripheral
blood is much smaller than the amount of stem
cells found in the bone marrow. Peripheral blood
stem cells can be used in either autologous or
allogeneic transplants. The majority of PBSC
transplants are autologous. However, recent clinical studies indicate that PBSCs are being used
more frequently than bone marrow for allogeneic
bone marrow transplantation.
The advantages of PBSC transplants when compared to bone marrow transplants are: in allogeneic
transplantation, haematopoietic and immune recovery are faster with PBSCs which reduces the potential
for disease recurrence, primarily graft-versus-hostdisease. In autologous transplantation, the use of
PBSCs can result in faster blood count recoveries.
Also, some medical conditions exist in which the recipient cannot accept bone marrow stem cell transplants,
but can accept PBSC transplants. Some possible disadvantages to PBSC transplant versus bone marrow
transplantation are: so much more fluid volume is
necessary to collect enough PBSCs that, at the time of
infusing the new stem cells into the recipient, the fluid
can collect in the lungs or cause temporary kidney
problems. Also, the time commitment for the donor
for a PBSC transplant is considerable. When the
PBSCs are being collected, several outpatient sessions
are needed and each session lasts approximately two–
four hours.
The transplant procedure
BONE MARROW TRANSPLANTATION. The bone

marrow extraction, or harvest, is the same whether
for an autologous or allogeneic transplant.
Harvesting is done under general anesthesia (i.e., the
donor sleeps through the procedure), and discomfort
is usually minimal afterwards. Bone marrow is drawn
from the iliac crest (the part of the hip bone to either
side of the lower back) with a special needle and a
syringe. Several punctures are usually necessary to
collect the needed amount of bone marrow, approximately 1–2 quarts (0.9–1.91). (This amount is only a
small percentage of the total bone marrow and is
typically replaced within four weeks.) The donor
remains at the hospital for 24–48 hours and can
resume normal activities within a few days.
GALE ENCYCLOPEDIA OF MEDICINE

If the bone marrow is meant for an autologous
transplant, it is stored at -112 to -320  F (-80 to
-196  C) until it is needed. Bone marrow for an allogeneic transplant is sometimes treated to remove the
donor’s T cells (a type of white blood cell) or to remove
ABO (blood type) antigens; otherwise, it is transplanted without modification.
The bone marrow is administered to the recipient
via a catheter (a narrow, flexible tube) inserted into a
large vein in the chest. From the bloodstream, it
migrates to the cavities within the bones where bone
marrow is normally stored. If the transplant is successful, the bone marrow begins to produce normal blood
cells once it is in place, or engrafted.
PERIPHERAL BLOOD STEM CELL TRANSPLANTATION. Before collection for a PBSC transplant,

donors receive daily four injections of the drug
G-CSF, or filgrastim. (Patients can give it to themselves at home if need be.) These pretreatments stimulate the body to release stem cells into the blood. After
these pretreatments, the donors’ experience is similar
to that of a whole blood donor’s experience— PBSC
donors’ blood is collected at a clinic or hospital as an
outpatient procedure. The differences are that several
sessions will be needed over days or weeks and the
blood is collected in a process called apheresis. The
blood travels from one arm into a blood cell separator
that removes only the stem cells, and the rest of the
blood is returned back to the donor, in the other arm.
The cells are then frozen for later use.
The PBSCs are administered to the recipient using
the same methods as those used in bone marrow transplantation. As stated, the amount of fluid with PBSCs
infused into the recipient’s body can be an issue.
Costs
Bone marrow transplantation is an expensive procedure. (Bone marrow donors are volunteers and do
not pay for any part of the procedure.) Insurance
companies and health maintenance organizations
(HMOs) may not cover the costs.

Preparation
A bone marrow transplant recipient can expect to
spend four to eight weeks in the hospital. In preparation
for receiving the transplant, the recipient undergoes
‘‘conditioning’’—a preparative regimen in which the
bone marrow and abnormal cells are destroyed.
Conditioning rids the body of diseased cells and
makes room for the marrow to be transplanted. It
typically involves chemotherapy and/or radiation
617

Bone marrow transplantation

Peripheral blood stem cell transplants

Bone marrow transplantation

treatment, depending on the disease being treated.
Unfortunately, this treatment also destroys healthy
cells and has many side effects such as extreme weakness, nausea, vomiting, and diarrhea. These side effects
may continue for several weeks.

Aftercare
A two- to four-week waiting period follows the
marrow transplant before its success can begin to be
judged. The marrow recipient is kept in isolation during this time to minimize potential infections. The
recipient also receives antibiotic medications and
blood and platelet transfusions to help fight off infection and prevent excessive bleeding. Further side
effects, such as nausea and vomiting, can be treated
with other medications. Once blood counts are normal
and the side effects of the transplant abate, the recipient is taken off antibiotics and usually no longer needs
blood and platelet transfusions.
Following discharge from the hospital, the recipient is monitored through home visits by nurses or outpatient visits for up to a year. For the first several
months out of the hospital, the recipient needs to be
careful in avoiding potential infections. For example,
contact with other people who may be ill should be
avoided or kept to a minimum. Further blood transfusions and medications may be necessary, but barring
complications, the recipient can return to normal
activities about 6–8 months after the transplant.

Risks
Bone marrow transplants are accompanied by
serious and life-threatening risks. Furthermore, they
are not always an absolute assurance of a cure for the
underlying ailment; a disease may recur in the future.
Approximately 30% of people receiving allogeneic transplants do not survive. Autologous transplants have a
much better survival rate—nearly 90%—but are not
appropriate for all types of ailments requiring a bone
marrow transplant. Furthermore, they have a higher
failure rate with certain diseases, specifically leukemia.
In the short term, there is the danger of pneumonia
or other infectious disease, excessive bleeding, or liver
disorder caused by blocked blood vessels. The transplant may be rejected by the recipient’s immune system,
or the donor bone marrow may launch an immunemediated attack against the recipient’s tissues. This
complication is called acute graft versus host disease,
and it can be a life-threatening condition. Characteristic
signs of the disease include fever, rash, diarrhea, liver
problems, and a compromised immune system.
618

Approximately 25–50% of bone marrow transplant recipients develop long-term complications.
Chronic graft versus host disease symptoms include
skin changes such as dryness, altered pigmentation,
and thickening; abnormal liver function tests;
dry mouth and eyes; infections; and weight loss.
Other long-term complications include cataracts (due
to radiation treatment), abnormal lung function, hormonal abnormalities resulting in reduced growth or
hypothyroidism, secondary cancers, and infertility.

Normal results
In a successful bone marrow transplant, the
donor’s marrow migrates to the cavities in the recipient’s bones and produces normal numbers of healthy
blood cells. Bone marrow transplants can extend a
person’s life, improve quality of life, and may aid in
curing the underlying ailment.
In autologous bone marrow transplantation, stem
cells are collected from the patient. Once the patient has
undergone chemotherapy, the cells are replaced in the
blood via an intravenous catheter. The cells return to the
bone marrow and begin producing healthy new cells.
Resources
PERIODICALS

Dreger, P., and N. Schmitz. ‘‘Allogeneic transplantation of
blood stem cells: coming of age?’’ Annals of Hematology
80, no. 3 (March, 2001): 127-36.
Nuzhat, Iqbal, Donna Salzman, Audrey J. Lazenby, et al.
‘‘Diagnosis of Gastrointestinal Graft-Versus-Host
Disease.’’ The American Journal of Gastroenterology 95
(November, 2000): 3034- 3038.
ORGANIZATIONS

American Society for Blood and Marrow Transplantation
(ASBMT). 85 W. Algonquin Road, Suite 550
Arlington Heights, IL 60005. (847) 427-0224.
mail@asbmt.org. Founded in 1990, a national professional association that promotes advancement of the
field of blood and bone marrow transplantation in
clinical practice and research.
Blood & Marrow Transplant Newsletter (Formerly BMT
Newsletter). 2900 Skokie Valley Road, Suite B,
Highland Park, IL 60035 (847) 433-3313. 1-888-5977674. help@bmtinfonet.org. <http://www2.bmtnews.
org>. Blood & Marrow Transplant Newsletter is a
not-for-profit organization that provides publications
and support services to bone marrow, peripheral blood
stem cell, and cord blood transplant patients and
survivors.
BMT Information <http://www.bmtinfo.org/>. Web site,
sponsored by a variety of other bone marrow transplant
organizations, lists basic information and resources
about bone marrow transplants.
GALE ENCYCLOPEDIA OF MEDICINE

Julia Barrett
Laura Ruth, Ph.D.

KEY TERMS
Radioisotope—A radioactive, or radiation-emitting
form, of an element.
Radionuclide—A substance which emits radiation
as it disintegrates.

Purpose
Bone scans are most frequently ordered to check
whether a cancer that originated elsewhere has spread
to the bones. Cancers that begin in the breasts,
kidneys, lungs, prostate, thyroid, or urinary bladder
are most likely to spread, or metastasize, to the bones.
If metastases are found, periodic bone scans may be
ordered to see if therapy is effective against a cancer.
Some cancers arise in bone. These are called primary bone cancers. When an abnormality is found on
an x ray of a bone, a bone scan may be helpful in
deciding if it is a primary bone cancer, or a non-cancerous (benign) condition.
Infection in the bone (osteomyelitis) can be
detected or confirmed by a bone scan, often days or
weeks before an x ray would reveal it. Bone scans are
useful in diagnosing early arthritic changes, and monitoring both the progression of the disease and the
effectiveness of treatment. Unexplained pain may be
evaluated with a bone scan, because it can demonstrate fractures that are difficult to detect on x ray.
Bone scans can be used to see if artificial joints have
loosened or become infected. Suspected child abuse
may be evaluated with a bone scan, due to its ability
to show an overall pattern of repeated trauma.
Abnormalities caused by altered circulation to the
bone may be diagnosed with a bone scan.

Precautions
Women who are pregnant or breastfeeding should
not have this test. A patient who is unable to remain
still for an extended period of time may require sedation for a bone scan.

I Bone nuclear medicine scan
Definition
A bone scan is a diagnostic procedure used to
evaluate abnormalities involving bones and joints. A
radioactive substance is injected intravenously, and
the image of its distribution in the skeletal system is
analyzed to detect certain diseases or conditions.
GALE ENCYCLOPEDIA OF MEDICINE

Description
This test is performed in a radiology facility, either
in a hospital department or an outpatient x-ray center.
The patient usually sits or lies down while a radioactive substance is injected through a vein in the arm.
For a bone scan, the radionuclide used is specifically
chosen to accumulate in the bone. The patient then
619

Bone nuclear medicine scan

Health Resources and Services Administration. 5600 Fishers
Lane, Rm. 14-45, Rockville, MD 20857, 301-443-3376,
comments@hrsa.gov. <http://www.hrsa.gov>.
HRSA manages contracts for the Organ Procurement
and Transplantation Network, Scientific Registry of
Transplant Recipients and National Marrow Donor
Program and provides public education and technical
assistance to increase donation. HRSA also monitors
the performance of the nation’s transplant centers and
provides potential transplant recipients with survival
rates and other vital information.
International Bone Marrow Transplant Registry/Autologous
Blood and Marrow Transplant Registry N. America.
Health Policy Institute, Medical College of Wisconsin.
8701 Watertown Plank Road, P.O. Box 26509,
Milwaukee, WI 53226 USA. (414) 456-8325.
ibmtr@mcw.edu. Voluntary organizations of more
than 400 institutions in 47 countries that submit data on
their allogeneic and autologous blood and marrow
transplant recipients to the IBMTR/ABMTR
Statistical Center at the Medical College of Wisconsin
in Milwaukee.
Leukemia & Lymphoma Society, Inc. 1311 Mamaroneck
Avenue White Plains, NY 10605. (914) 949-5213.
<http://www.leukemia-lymphoma.org/>. National
voluntary health agency dedicated to curing leukemia,
lymphoma, Hodgkin’s disease and myeloma, and to
improving the quality of life of patients and their
families.
National Marrow Donor Program. Suite 500, 3001 Broadway
Street Northeast, Minneapolis, MN 55413-1753. (800)
MARROW-2. <http://www.marrow.org>. Founded in
1986, The National Marrow Donor Program (NMDP) is
a non-profit international leader in the facilitation of
unrelated marrow and blood stem cell transplantation.
National Organ and Tissue Donation Initiative. <http://
www.organdonor.gov/>. Created by Health Resources
and Services Administration (HRSA) Department of
Health and Human Services (DHHS) <http://
www.os.dhhs.gov/>. Provides information and
resources on organ donation and transplantation issues.

Bone nuclear medicine scan

waits from three to four hours, for the substance to
collect within the skeletal system. During this time, he
or she will be instructed to drink several glasses of
water. Patients are free to get up and move around as
they desire during this waiting time, and should urinate frequently. Just before the scanning begins, the
patient should empty his or her bladder again. This
ensures that a lot of radioactive material is not concentrated in the urinary bladder, which could obscure
part of the pelvic bones.
During the scan, the patient lies on his or her back
on a table, but may be repositioned to the stomach or
side during the study. It is important for the patient not
to move, except when directed to by the technologist.
The radionuclide scanner, sometimes called a
gamma camera, or scintillation camera, is positioned
against the body part to be examined. Either the camera, the table, or both, may change position during
the study. For a total body bone scan, the patient is
scanned from head to foot, over a period of 30-60
minutes. Patients should experience no discomfort
from this examination.
A special kind of bone scan, called a SPECT
(Single Photon Emission Computed Tomography)
scan may be added, to study a particular part of the
body in more detail. Suspected diseases of the hips,
lower back, or jaw are often evaluated using this study.
It usually takes an additional 30-45 minutes. The camera circles completely around the area in question or
multiple cameras are used to create a cross-sectional
image. This helps pinpoint the location of the abnormality being evaluated.
The bone scan might be done in phases. The procedure is the same, except the scanning takes place
immediately after the radioactive substance is injected,
then again at set intervals to image how the radioactive
tracer pools and distributes in the body and bone. For
example, a two-phase bone scan for osteomyelitis may
involve a scan about five minutes after injection, then
about three hours later.

radionuclide scanner does not emit any radiation at all,
but detects and records it from the patient.

Aftercare
Fluids are encouraged after the scan to aid in the
excretion of the radioisotope. It is almost completely
eliminated from the body within 24 hours. However,
since increased airport security methods resulting from
the September 11, 2001 attacks, isolated cases of people
who have had recent diagnostic nuclear medicine procedures setting off airport security systems have
occurred. One state’s Homeland Security Department
has warned people having nuclear medicine procedures
and flying soon afterward to bring adequate documentation of the procedure along to the airport.

Normal results
The normal appearance of the scan will vary
according to the patient’s age. In general, a uniform
concentration of radionuclide uptake is present in all
bones in a normal scan.

Abnormal results
A high concentration of radionuclide occurs in
areas of increased bone activity. These regions appear
brighter and may be referred to as ‘‘hot spots.’’ They
may indicate healing fractures, tumors, infections, or
other processes that trigger new bone formation. Lower
concentrations of radionuclide may be called ‘‘cold
spots.’’ Poor blood flow to an area of bone, or bone
destruction from a tumor may produce a cold spot.
The bone scan is a very sensitive test and can detect
subtle conditions more readily than other studies.
However, it is not a very specific examination, and
often cannot distinguish exactly what disease process
is causing an abnormality. Results need to be correlated
with the patient’s medical history, and other radiologic
and laboratory studies to make a definite diagnosis.
Resources

Preparation

PERIODICALS

Some specialized blood studies should be drawn
before this study is begun. Jewelry or metallic objects
need to be removed. No other special physical preparation is required.

Frank, John. ‘‘Introduction to Imaging: Bone and Joint.’’
Student BMJ March 2004: 101–105.
Gebhart, Fred. ‘‘Nuclear Medicine Creating Patient Travel
Problems.’’ Drug Topics July 28, 2004: 11.

The patient should understand that there is no
danger of radioactive exposure to themselves or others,
as only small amounts of the radioisotope are used. The
total dose of radiation absorbed is minimal, often less
than the amount received from ordinary x rays. The

Ellen S. Weber, MSN
Teresa G. Odle

620

Bone tumor see Sarcomas
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Bone x rays are a diagnostic test in which ionizing
radiation passing through the bones being examined
enables an image to be produced on film.

Purpose
Bone x rays are ordered to detect disease or injury
to the bone such as broken bones, tumors, and other
problems. They can determine bone density, texture,
erosion, and changes in bone relationships. Bone x rays
also evaluate the joints for diseases such as osteoarthritis.

Precautions
Precautions should be taken to protect patients
from unnecessary exposure to radiation. Patients should
be shielded with lead aprons as much as possible.
Women of childbearing age who could be pregnant
should not have x rays of their trunk or pelvic regions.
The fetus is especially at risk during the first trimester of
pregnancy. Women who are pregnant should not have x
rays of their pelvic region, lumbar spine, and abdomen
unless absolutely necessary. If other types of x rays are
necessary, a lead apron should be used to shield the
abdominal and pelvic regions.

Description
X rays are a common diagnostic test in which a
form of energy called x-ray radiation penetrates the
patient’s body. In bone x rays, electrical current passes
through an x-ray tube and produces a beam of ionizing
radiation that passes through the bone(s) being examined. This produces a picture of the inside of the body
on film. The physician reads the developed x ray on a
wall-mounted light box.
Digital x rays are a new type of x ray in which
conventional equipment is used to take the x ray but
the image is produced via computer. In a digital x ray,
the image is created on a reusable plate. After being
read by a laser reader, the information is sent in digital
form to a storage unit connected to a computer network
from which the radiologist reads the image. An electronic report can then be sent to the patient’s physician.
Problems with bones that x rays can detect result
from injury or from disease caused by a malfunction in
the patient’s bone chemistry. Bone injuries, especially
broken bones (fractures), are common and can be
accurately diagnosed by bone x rays. X rays are
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Arthritis—A disease of the joints that arises from
wear and tear, age and less often from inflammation.
Osteogenesis imperfecta—Also called brittle bones,
this is a condition present at birth in which bones are
abnormally fragile, brittle and break easily.
Osteomalacia—A disease in which bones gradually soften and bend.
Osteomyelitis—An infection of the bone marrow
and the bone.
Osteoporosis—A disease that occurs primarily in
post-menopausal women in which the amount of
bone is reduced or skeletal tissue wastes away.
Paget’s disease—A disease, whose cause is
unknown, which is generally found in older people. Symptoms include bone pain, bowed legs,
curves spine, and broken bones. Another name for
this disease is osteitis deformans.

especially helpful in diagnosing simple and incomplete
fractures that can’t be detected during a physical
examination. X rays can also be used to check for
bone position in a fracture. Some bone diseases can
be definitively diagnosed with bone x rays while others
require additional tests.
Osteoporosis, a common bone disease, can be
detected in bone x rays but other tests are then ordered
to determine the extent of the disease. For osteomalacia and rickets, a blood test and x rays of the affected
bone are usually definitive; in some cases a bone biopsy
(microscopic analysis of a small amount of tissue) is
also done. In a rare bone disease called Paget’s disease,
x rays may be used in conjunction with bone, blood,
and urine tests to make a diagnosis. In another rare
bone disease, fibrous dysplasia, bone x rays or a bone
biopsy (microscopic analysis of a small amount of
tissue) are used to confirm the diagnosis. Bone x rays
are definitive in diagnosing osteogenesis imperfecta.
For osteomyelitis, bone x rays are used in conjunction
with a blood test, bone scan, or needle biopsy to make
the diagnosis. For arthritis, x rays of the bone are
occasionally used in conjunction with blood tests.
For bone tumors, bone x rays are helpful but they
may not be definitive.
Bone x rays are performed by a technologist, and
interpreted by a radiologist. They are taken in a physician’s office, radiology department, outpatient clinic, or
diagnostic clinic. Bone x rays generally take less than
621

Bone x rays

I Bone x rays

Botulinum toxin injections

10 minutes. There is no pain or discomfort associated
with the test, but some people find it difficult to remain
still. The results are often available in minutes.
During the test, the patient lies on a table. The
technologist taking the x ray will check the patient’s
positioning and place the x-ray machine over the part
of the body being examined. After asking the patient
to remain motionless, he or she steps out of the area
and presses a button to take the picture.

Preparation
The patient is asked to remove clothing, jewelry,
and any other metal objects from the area being x rayed.
If appropriate, a lead shield will be placed over other
body parts to minimize exposure to radiation.

Aftercare
The patient can immediately resume normal
activities.

Resources
PERIODICALS

Frank, John. ‘‘Introduction to Imaging: Bone and Joint.’’
Student BMJ (March 2004): 101–105.

Lori De Milto
Teresa G. Odle

Borderline personality disorder see
Personality disorders
Bordetella pertussis infection see Whooping
cough
Borrelia burgdorferi infection see Lyme
disease
Botanical medicine see Herbalism, western
Botox injections see Botulinum toxin
injections

Risks
The human body contains some natural radiation and is also exposed to radiation in the environment. There is a slight risk from exposure to radiation
during bone x rays, however, the amount of radiation
is small and the risk of harm is very low. If reproductive organs are exposed to radiation, genetic
alterations may occur. Excessive or repeated doses
of radiation can cause changes in other types of
body tissue. No radiation remains in the body after
the x ray.

Normal results
Normal bones show no fractures, dislocations, or
other abnormalities.

Abnormal results
Results that indicate the presence of bone injury
or disease differ in appearance according to the nature
of the injury/disease. For example, fractures show up
as clear breaks in the bones, while osteoporotic bone
has the same shape as a normal bone on an x ray but is
less dense. Even though a bone x ray may not show
definite results, it often is the first imaging choice, to be
followed up by another imaging technique such as
magnetic resonance imaging (MRI). Bone x rays are
still the easiest was to show a typical bone fracture and
to check on healing of broken bones.
622

I Botulinum toxin injections
Definition
Botulinum is a bacterium (Clostridium botulinum)
that produces seven different toxins that can cause
botulism and is also medically used to block muscle
contractions.

Purpose
Botulinum toxin (Botox) injection is used in
conditions of excessive and inappropriate muscle
contraction, spasticity (persistent states of muscle
contraction), sphincter contraction, eye-movement
disorders, tics and tremors, and cosmetically to
treat facial lines and wrinkles. The FDA approved
Botox for treating excessive underarm sweating in
2004.
Botox has also been used in the treatment of
chronic muscle tension and migraine headaches. The
relief is likely due to the decrease in localized muscle
spasms, as no direct effect of Botox on the sensory
nerves has been established. Researchers in New
Zealand were testing Botox as means to help improve
movement in children with a form of cerebral palsy
called hemiplegia in 2004. The application of the therapy seems to be growing continuously beyond its more
popularly known cosmetic uses.
GALE ENCYCLOPEDIA OF MEDICINE

Antibodies—A protein developed in response to
the presence of a foreign substance.
Immunoresistance—The presence of circulating
antibodies.
Neuromuscular junction—Interface between
motor nerve ending and muscle tissue.
Serotype—Microorganisms differing in the type of
surface antigens.
Antigen—A foreign substance inducing an antibody response within the body.

Precautions
Botulinum toxin is produced from the bacterium
that causes food poisoning in humans. High doses of
the toxin can be fatal; however, doses administered
therapeutically are so small that harmful effects are
uncommon.

Description
The number of potential applications for botulinum toxin extends to every muscle group. The first
therapeutic use of Botox was in the treatment of
strabismus (eyes are unable to direct toward the same
object) and since then it has been used to treat a variety
of involuntary muscle contractions or disorders. Its
cosmetic use is the result of treatment for facial spasms
where smoothing of facial lines was reported by
patients. In general, 90% of injections for facial
spasms are resolved satisfactorily.
Toxin type A has a duration of effect that lasts
approximately three months and is the therapeutic
agent of choice for most conditions.

Preparation
The dosage of Botox must be monitored and
adjusted, with multiple injections showing a lower
incidence of complications versus administration by
one larger dose.

Risks
In over 30 years of therapeutic use in humans,
botulinum toxin has proven to be remarkably safe.
Difficulties associated with administration of toxin
are: different patients may experience different effects
at the same dose, patients new to the treatment may
GALE ENCYCLOPEDIA OF MEDICINE

experience exaggerated effects at subsequent visits
and/or neighboring muscles may become activated at
subsequent treatments. Patients should ask about
their provider s experience with injecting Botox before
proceeding with the procedure.
Additional side effects may include excessive muscle weakness at the injection site or adjacent muscles.
These effects typically resolve quickly. Occasionally,
patients report flu-like symptoms but they are usually
self-limited.
A certain percentage of patients may also experience resistance to the toxin. The presence of circulating antibodies to the toxin is presumed to be the
primary reason for resistance to Botox injections.
Patients who have little reaction to Botox ‘A’ may
benefit from injections using one of the other six
serotypes. Using the smallest effective dose limits the
likelihood of immunoresistance in unresponsive
patients.

Normal results
The anticipated outcome of Botox injections is
relaxation of the target muscle tissue. The pharmacological effects of botulinum toxin are typically isolated
to local areas and do not result in tissue destruction or
prolonged paralysis. Varying the dose can deliver a
precise amount of toxin to achieve graded degrees of
paralysis for the desired level of response.

Abnormal results
Most side effects, such as weakness in the injected
muscle or overall muscle soreness, will go away
quickly. Some patients have received too much of the
substance when having Botox for cosmetic purposes
and have been unhappy with the results. Physicians
and patients should discuss the procedure and the
amount to be used. Many clinicians believe that it is
best to err on the side of low dosage with a return trip
for more, rather than too high a dosage that might
result in unwanted cosmetic effects.
Resources
BOOKS

Blitzer, A., W. J. Binder, J. Brian Boyd, and Alastair
Carruthers. Management of Facial Lines and Wrinkles.
Philadelphia: Lippincott Williams & Wilkins, 1999.
Brin, M.F. Botulinum Toxin Therapy: Basic Science and
Overview of Other Therapeutic Applications.
Department of Neurology, Movement Disorders
Program, The Mount Sinai Medical Center, New York,
New York 10029.

623

Botulinum toxin injections

KEY TERMS

Botulism

PERIODICALS

‘‘Another Botox Use.’’ Dermatology Times (October 2004): 24.
Franklin, Deeanna. ‘‘Separate Fact from Fiction With
Botox Techniques, Safety.’’ Skin & Allergy News
(August 2004): 41.
Johnson, Kate. ‘‘FDA Approves Botox for Severe Underarm
Sweating.’’ Family Practice News (September 1, 2004): 13.
OTHER

Blitzer A and L. Sulica. ‘‘Botulinum toxin: basic science and
clinical uses in otolaryngology.’’ New York Center for
Voice and Swallowing Disorders, St. Luke’s Roosevelt
Hospital Center.

Bonny McClain, DC
Teresa G. Odle

I

Botulism

Definition
Botulism is caused by botulinum toxin, a natural
poison produced by certain bacteria in the Clostridium
genus. Exposure to the botulinum toxin occurs mostly
from eating contaminated food, or in infants, from
certain clostridia growing in the intestine. Botulinum
toxin blocks motor nerves’ ability to release acetylcholine, the neurotransmitter that relays nerve signals to
muscles, and flaccid paralysis occurs. As botulism
progresses, the muscles that control the airway and
breathing fail.

Description
Botulism occurs rarely, but it causes concern
because of its high fatality rate. Clinical descriptions
of botulism possibly reach as far back in history as
ancient Rome and Greece. However, the relationship
between contaminated food and botulism wasn’t
defined until the late 1700s. In 1793 the German physician, Justinius Kerner, deduced that a substance in
spoiled sausages, which he called wurstgift (German
for sausage poison), caused botulism. The toxin’s origin
and identity remained elusive until Emile von
Ermengem, a Belgian professor, isolated Clostridium
botulinum in 1895 and identified it as the poison source.
Three types of botulism have been identified: foodborne, wound, and infant botulism. The main difference between types hinges on the route of exposure to
the toxin. In the United States, there are approximately
110 cases of botulism reported annually. Food-borne
botulism accounts for 25% of all botulism cases and
624

usually can be traced to eating contaminated homepreserved food. Infant botulism accounts for 72% of
all cases, but the recovery rate is good (about 98%)
with proper treatment. From 1990 to 2000, 263 cases of
food-borne cases were reported in the United States,
most of them in Alaska. Though most were related to
home canning, two restaurant-associated outbreaks
affected 25 people.
Though domestic food poisoning is a problem
world-wide, there has been a growing concern regarding the use of botulism toxin in biological warfare and
terrorist acts. The Iraqi government admitted in 1995
that it had loaded 11,200 liters of botulinum toxin into
SCUD missiles during the Gulf War. Luckily, these
special missiles were never used. As of 1999, there
were 17 countries known to be developing biological
weapons, including the culture of botulism toxins.

Causes and symptoms
Toxin produced by the bacterium Clostridium botulinum is the main culprit in botulism. Other members of
the clostridium genus can produce botulinum toxin,
namely C. argentinense, C. butyricum, and C. baratii,
but they are minor sources. To grow, these bacteria
require a low-acid, oxygen-free environment that is
warm (40-120  F or 4.4–48.8  C) and moist. Lacking
these conditions, the bacteria transform themselves into
spores that, like plant seeds, can remain dormant for
years. Clostridia and their spores exist all over the world,
especially in soil and aquatic sediments. They do not
threaten human or animal health until the spores
encounter an environment that favors growth. The
spores then germinate, and the growing bacteria produce
the deadly botulism toxin.
Scientists have discovered that clostridia can produce at least seven types of botulism toxin, identified
as A, B, C, D, E, F, and G. Humans are usually
affected by A, B, E, and very rarely F. Domesticated
animals such as dogs, cattle, and mink are affected by
botulism C toxin, which also affects birds and has
caused massive die-offs in domestic bird flocks and
wild waterfowl. Botulism D toxin can cause illness in
cattle, and horses succumb to botulism A, B, and C
toxin. There have been no confirmed human or animal
botulism cases linked to the G toxin.
In humans, botulinum toxin latches onto specific
proteins in nerve endings and irreversibly destroys
them. These proteins control the release of acetylcholine,
a neurotransmitter that stimulates muscle cells. With
acetylcholine release blocked, nerves are not able to stimulate muscles. Ironically, botulinum toxin has found a
beneficial niche in the world of medicine due to this
GALE ENCYCLOPEDIA OF MEDICINE

Acetylcholine—A chemical released by nerve cells
to signal other cells.
Antitoxin—A substance that inactivates a poison
(e.g., toxin) and protects the body from being
injured by it.

muscle is partially paralyzed and normal movement is
retained. This is commonly referred to as Botox injection.
The three types of human botulism include the
following symptoms:


Food-borne. Food that has been improperly preserved or stored can harbor botulinum toxin-producing
clostridia. Botulism symptoms typically appear within
18-36 hours of eating contaminated food, with
extremes of four hours to eight days. Initial symptoms
include blurred or double vision and difficulty swallowing and speaking. Possible gastrointestinal problems
include constipation, nausea, and vomiting. As botulism
progresses, the victim experiences weakness or paralysis, starting with the head muscles and progressing
down the body. Breathing becomes increasingly difficult. Without medical care, respiratory failure and death
are very likely.



Infant. Infant botulism was first described in 1976.
Unlike adults, infants younger than 12 months are
vulnerable to C. botulinum colonizing the intestine.
Infants ingest spores in honey or simply by swallowing spore-containing dust. The spores germinate in
the large intestine and, as the bacteria grow, they
produce botulinum toxin that is absorbed into the
infant’s body. The first symptoms include constipation, lethargy, and poor feeding. As infant botulism
progresses, sucking and swallowing (thus eating)
become difficult. A nursing mother will often notice
breast engorgement as the first sign of her infant’s
illness. The baby suffers overall weakness and cannot
control head movements. Because of the flaccid
paralysis of the muscles, the baby appears ‘‘floppy.’’
Breathing is impaired, and death from respiratory
failure is a very real danger.



Wound. Confirmed cases of wound botulism have
been linked to trauma such as severe crush injuries to
the extremities, surgery, and illegal drug use. Wound
botulism occurs when clostridia colonize an infected
wound and produce botulinum toxin. The symptoms
usually appear four to 18 days after an injury occurs
and are similar to food-borne botulism, although
gastrointestinal symptoms may be absent.

CT scan—The abbreviated term for computed or
computerized axial tomography. The test may involve
injecting a radioactive contrast into the body.
Computers are used to scan for radiation and create
cross-sectional images of internal organs.
Electromyographic test—A medical test which
determines if a muscle’s response to electrical stimuli. The test results allow medical personnel to
assess how nerves to the muscle are functioning.
Flaccid paralysis—Paralysis characterized by limp,
unresponsive muscles.
Lumbar puncture—A procedure in which a small
amount of cerebrospinal fluid is removed from the
lower spine. Examination of this fluid helps diagnose certain illnesses.
MRI—The abbreviated term for magnetic resonance imaging. MRI uses a large circular magnet
and radio waves to generate signals from atoms
in the body. These signals are used to construct
images of internal structures.
Neurotransmitter—A chemical found in nerves that
relays nerve signals to other cells. Acetylcholine is a
neurotransmitter.
Sepsis—The presence of infection-causing organisms or associated toxins in the blood or within
body tissues.
Spores—A state of ‘‘suspended animation’’ that
some bacteria can adopt when conditions are not
ideal for growth. Spores are analogous to plant
seeds and can germinate into growing bacteria
when conditions are right.
Toxin—A poisonous substance produced by a
microorganism, plant, or animal.
Tracheostomy—The procedure used to open a
hole in the neck to the trachea, or windpipe. It is
sometimes used in conjunction with a respirator.

action. Certain medical disorders are characterized by
involuntary and uncontrollable muscle contractions.
Medical researchers have discovered that injecting a
strictly controlled dose of botulinum toxin into affected
muscles inhibits excessive muscle contractions. The
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Diagnosis of botulism can be tricky because symptoms mimic those presented by other diseases. Botulism
may be confused with Guillain-Barre syndrome,
myasthenia gravis, drug reactions, stroke, or nervous
system infection, intoxications (e.g. carbon monoxide
or atropine), or shellfish poisoning. Sepsis is the most
common initial diagnosis for infant botulism. Failure to
thrive may also be suspected. Some reports have linked
625

Botulism

KEY TERMS

Botulism

infant botulism to 5-15% of sudden infant death syndrome (SIDS, crib death) cases. Laboratory tests are
used for definitive diagnosis, but if botulism seems
likely, treatment starts immediately.
While waiting for laboratory results, doctors ask
about recently consumed food and work to dismiss
other disease possibilities. A physical examination is
done with an emphasis on the nervous system. As part
of this examination, CT scans, MRIs, electromyographic tests, or lumbar punctures may be ordered.
Laboratory tests involve testing a suspected food and/
or the patient’s serum, feces, or other specimens for
traces of botulinum toxin or clostridia.

Treatment
Drugs
Adults with botulism are treated with an antitoxin
derived from horse serum that is distributed by the
Centers for Disease Control and Prevention. The antitoxin (effective against toxin types A, B, and E) inactivates only the botulinum toxin that is unattached to
nerve endings. Early injection of antitoxin (usually
within 24 hours of onset of symptoms) can preserve
nerve endings, prevent progression of the disease, and
reduce mortality.
Infants, however, cannot receive the antitoxin
used for adults. For them, human botulism immune
globulin (BIG) is available in the United States
through the Infant Botulism Treatment and
Prevention Program in Berkeley, California. BIG neutralizes toxin types A, B, C, D, and E before they can
bind to nerves. This antitoxin can provide protection
against A and B toxins for approximately four
months. Though many infants recover with supportive care, BIG cuts hospital stay in half, and therefore
reduces hospital costs by 50% as well.
Aside from antitoxin, no drugs are used to treat
botulism. Antibiotics are not effective for preventing
or treating botulism. In fact, antibiotic use is discouraged for infants because dying bacteria could potentially release more toxin into a baby’s system.
Antibiotics can be used, however, to treat secondary
respiratory tract and other infections.
Respiratory support
Treatment for infants usually involves intensive
respiratory support and tube feeding for weeks or
even months. Once an infant can breathe unaided,
physical therapy is initiated to help the child relearn
how to suck and swallow. A respirator is often required
to help adult patients breathe, and a tracheostomy may
also be necessary.
626

Surgery
Surgery may be necessary to clean an infected
wound and remove the source of the bacteria that is
producing the toxin. Antimicrobial therapy may be
necessary.
Gastric lavage
When botulism is caused by food, it often is necessary to flush the gastrointestinal tract (gastric lavage).
Often cathartic agents or enemas are used. It is important to avoid products that contain magnesium,
since magnesium enhances the effect of the toxin.

Prognosis
With medical intervention, botulism victims can
recover completely, though slowly. It takes weeks to
months to recover from botulism, and severe cases
can take years before a total recovery is attained.
Recovery depends on the nerve endings building
new proteins to replace those destroyed by botulinum
toxin.

Prevention
Vaccines against botulism do not exist to prevent infant botulism or other forms of the disease.
However, scientists announced in 2004 that they
had successfully vaccinated mice and ducks against
type C and D, which may help lead to vaccines for
humans. Food safety is the surest prevention for botulism. Botulinum toxin cannot be seen, smelled, or
tasted, so the wisest course is to discard any food that
seems spoiled without tasting it. Home canners must be
diligent about using sterile equipment and following
U.S. Department of Agriculture canning guidelines. If
any part of a canned food container is rusty or bulging,
the food should not be eaten. Infant botulism is difficult to prevent, because controlling what goes into an
infant’s mouth is often beyond control, especially in
regard to spores in the air. One concrete preventive is
to never feed honey to infants younger than 12 months
since it is one known source of botulism spores. As
infants begin eating solid foods, the same food precautions should be followed as for adults.
Resources
PERIODICALS

Cadou, Stephanie G. ‘‘Diagnosing Infant Botulism.’’ The
Nurse Practitioner 26, no.3 (March 2001): 76.
Shapiro, Roger L. and David L. Swerdlow. ‘‘Botulism: Keys
to Prompt Recognition and Therapy.’’ Consultant
(April 1999): 1021–1024.
GALE ENCYCLOPEDIA OF MEDICINE

Janie F. Franz
Teresa G. Odle

Bowel preparation

Sobel, Jeremy, et al. ‘‘Foodborne Botulism in the United
States, 1990–2000.’’ Emerging Infectious Diseases
(September 2004): 1606–1612.
‘‘Vaccination With Botulinum Neurotoxin Fragments
Prevents Botuism.’’ Obesity, Fitness & Wellness Week
(August 7, 2004): 117.

KEY TERMS
Lesion— An abnormal change in tissues.
Polyp— A growing mass of tissue.



relieving a twisted bowel

Bovine spongiform encephalopathy see
Creutzfeldt-Jakob disease



foreign body removal



treating bleeding lesions

Bowel incontinence see Fecal incontinence



preventive surveillance of cancer in patients with a
positive family history of colon cancer

Precautions

I Bowel preparation
Definition
Bowel preparation is a procedure usually undertaken before a diagnostic procedure or treatment can be
initiated for certain colorectal diseases. Bowel preparation is a cleansing of the intestines from fecal matter and
secretions.

Antibiotic prophylaxis is not routinely recommended. In some cases of prosthetic heart valves,
antibiotics can be prescribed. Evidence exists that
evacuation of intestinal waste products in conjunction
with antibiotics before (prophylactic) the procedure
reduces the possibility of sepsis (infection which
spreads from the primary site to blood).

Description
Purpose
The ultimate goal of bowel preparation is to empty
and cleanse the bowel for a diagnostic procedure (using
x rays to detect a disease process in the intestines) or for
surgical intervention (such as removal of polyps, cancer,
or narrowing of the intestinal diameter). Colonoscopy is
an effective treatment procedure for polyps (a growing
mass of tissue). This procedure enables the doctor to
visualize the entire large bowel. During a colonoscopy,
polyps can be cauterized (applying an electric current
which incinerates the polyp). The procedure can be both
diagnostic and therapeutic. A sigmoidoscopy scope is a
flexible tube that allows clinicians to view the sigmoid
colon (the part of the large intestine before the rectum).
This procedure is important for detection of colorectal
cancer. It is safe, quick to perform (usually 30–45 minutes in about 90% of cases), and an effective diagnostic
tool for evaluation of:

The bowel is emptied of any contents for such
procedures as barium enema (introducing a compound
containing barium to promote better visualization of
intestines during x rays) or colonoscopy. Preparation of
the bowel distally—from the rectum—is necessary for
such diagnostic procedures as sigmoidoscopy. Bowel
emptying is done through taking oral laxative solutions
that speed up the excretion of the contents of the lower
bowel together with restrictions on solid food intake.
A newer type of imaging study may eventually
make current laxative methods of bowel preparation
obsolete. According to a group of researchers in the
United Kingdom, computed tomography (CT) colonography (sometimes called virtual colonoscopy) has
shown itself to be as accurate in diagnosing colorectal
tumors as optical colonoscopy. CT colonography
allows a radiologist to examine the colon and nearby
organs in less than 30 seconds.



rectal bleeding



other abnormalities detected by imaging studies



removal of polyps



biopsy



evaluation of chronic diarrhea or inflammatory
bowel disease



recurrences of colorectal cancer or polyps

Bowel preparation for visualization of the colon is
performed to ensure the procedure will be accurate and
complete. There are several effective cleansing preparations including polyethylene glycol solution (Colyte),
sodium phosphate solution (Phospho-Soda), magnesium citrate with bisacodyl tablets, and castor oil with

GALE ENCYCLOPEDIA OF MEDICINE

627

Preparation

Bowel preparation

bisacodyl tablets. One of these preparations should be
administered starting at 4:00 p.m. the day before the
procedure. Patients are usually asked to avoid solid
foods for about 36 hours before diagnostic procedures.
Such clear liquids as vegetable or beef broth, apple or
white grape juice, soda pop or fruit-flavored gelatin are
permitted, although some doctors ask patients to avoid
red-colored beverages or gelatin flavors on the grounds
that the red food coloring in these products may make
bleeding more difficult to detect.
In most cases, patients may continue to take other
prescription medications at the usual times while they
are restricted to clear liquids. It is a good idea, however, to check with the doctor beforehand.

Aftercare
Patients should have a friend or relative to drive
them home after the procedure, as the combination of
a period of dietary restriction, frequent bowel movements, and the procedure itself leaves most people
feeling tired and slightly weak. Many doctors advise
patients to postpone vigorous physical activity or
work requiring mental concentration until the day
after the procedure. Patients can resume eating solid
foods as soon as they get home.
Some patients may notice a small amount of blood
on toilet tissue or underwear following a colonoscopy
or other examination of the lower digestive tract.
Spotting is not cause for concern; however, patients
who have steady or heavy bleeding from the rectum
should call their doctor as soon as possible.

Risks
The current standard of care dictates that patients
receive antibiotic prophylaxis if they are at increased risk
of developing an infection. High-risk patients include
those with cardiac diseases or patients with prostheses.
Bowel preparation can be stressful for some
patients, particularly those with pre-existing nutritional problems associated with cancer treatment or
malabsorption. In addition, many patients find the
various oral solutions unpleasant to the taste and
difficult to swallow for that reason. According to one
British study, oral solutions flavored with lemon are
more acceptable to patients than unflavored forms.
Both Colyte and Phospho-Soda are available with
flavoring added; patients may wish to ask their pharmacist for these specific products. Mild nausea, vomiting, stomach cramps, intestinal gas, dry mouth, and
increased thirst are common side effects of these products. Some patients are helped by taking an electrolyte
628

supplement along with oral sodium phosphate solution to lower the risk of dehydration.
Some people may have severe allergic reactions
to commonly used oral laxatives used for bowel preparation. Patients who develop hives, swelling of the
face or hands, swelling or tingling in the throat or
mouth, difficulty breathing, or tightness in the chest
should call their doctor at once. This type of reaction is
a medical emergency.

Normal results
Absence of anatomical changes or abnormalities
in the intestines would result in normal diagnosis.

Abnormal results
Polyps can be treated with electrocautery. A
biopsy is taken of any suspicious polyps and further
analyzed. Sigmoidoscopy can detect masses, bleeding,
and ulcerative disease.
Resources
BOOKS

Tierney, Lawrence M., et al, editors. Current Medical
Diagnosis and Treatment 2001. 40th ed. New York:
McGraw-Hill, 2001.
Wilson, Billie A., Margaret T. Shannon, and Carolyn L.
Stang. Nurses Drug Guide 2000. Stamford, CT:
Appleton & Lange, 2000.
PERIODICALS

Bulmer, Frances M. ‘‘Bowel Preparation for Rectal and
Colonic Investigation.’’ Nursing Standard 14 (February
2000): 32–35.
Burling, D., S. Taylor, and S. Halligan. ‘‘Computerized
Tomography Colonography.’’ Expert Review of
Anticancer Therapy 4 (August 2004): 615–625.
Tjandra, J. J., and P. Tagkalidis. ‘‘Carbohydrate-Electrolyte
(E-Lyte) Solution Enhances Bowel Preparation with
Oral Fleet Phospho-Soda.’’ Diseases of the Colon and
Rectum 47 (July 2004): 1181–1186.
ORGANIZATIONS

American College of Gastroenterology. 4900 B South 31st
Street, Arlington, VA 22206. (703) 820-7400. <http://
www.acg.gi.org/ct_html>.
American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814. (301)
657-3000. <http://www.ashp.org>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <http://www.fda.gov>.

Laith Farid Gulli, M.D.
Bilal Nasser, M.Sc.
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Definition

Diverticulum—Small tubes or pouches that project
off the wall of the intestine, visible as opaque on an
x ray after the patient has swallowed a contrast
(dye) substance.

A bowel resection is a surgical procedure in which
a part of the large or small intestine is removed.

Embolism—Blockage of a blood vessel by any small
piece of material traveling in the blood. The emboli
may be caused by germs, air, blood clots, or fat.
Ischemia—A compromise in blood supply to body
tissues that causes tissue damage or death.

Purpose
Bowel resection may be performed to treat various disorders of the intestine, including cancer,
obstruction, inflammatory bowel disease, ruptured
diverticulum, ischemia (compromised blood supply),
or traumatic injury.

Ostomy—A surgically-created opening in the abdomen for elimination of waste products (urine or stool).

Description
The preferred type of bowel resection involves
removal of the diseased portion of intestine, and surgically re-joining the remaining ends. In this procedure, the continuity of the bowel is maintained and
normal passage of stool is preserved. When deemed
necessary by the surgeon, the diseased portion of the
bowel may be removed, and the functioning end of
the intestine may be brought out onto the surface of
the abdomen, forming an temporary or permanent
ostomy. Use of the large intestine to form the ostomy
results in a colostomy; use of small intestine to form the
ostomy results in an ileostomy.

Preparation
As with any surgical procedure, the patient will be
required to sign a consent form after the procedure is
explained thoroughly. Blood and urine studies, along
with various x rays and an electrocardiogram (EKG)
may be ordered as the doctor deems necessary. In
order to empty and cleanse the bowel, the patient
may be placed on a low residue diet for several days
prior to surgery. A liquid diet may be ordered for at
least the day before surgery, with nothing taken by
mouth after midnight. A series of enemas and/or oral
preparations (GoLytely or Colyte), may be ordered to
empty the bowel of stool. Oral anti-infectives (neomycin, erythromycin, or kanamycin sulfate) may be
ordered to decrease bacteria in the intestine and help
prevent post-operative infection. A nasogastric tube is
inserted through the nose into the stomach on the day
of surgery or during surgery. This removes the gastric
secretions and prevents nausea and vomiting. A urinary
catheter (thin tube inserted into the bladder) may also
be inserted to keep the bladder empty during surgery,
giving more space in the surgical field and decreasing
chances of accidental injury.
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
Post-operative care for the patient who has had a
bowel resection, as with those who have had any major
surgery, involves monitoring of blood pressure, pulse,
respirations, and temperature. Breathing tends to be
shallow because of the effect of anesthesia and the
patient’s reluctance to breathe deeply and experience
pain that is caused by the abdominal incision. The
patient is instructed how to support the operative site
during deep breathing and coughing, and is given pain
medication as necessary. Fluid intake and output is
measured, and the operative site is observed for color
and amount of wound drainage. The nasogastric tube
will remain in place, attached to low intermittent suction until bowel activity resumes. Fluids and electrolytes are infused intravenously until the patient’s diet
can gradually be resumed, beginning with liquids and
advancing to a regular diet as tolerated. The patient is
generally out of bed approximately eight to 24 hours
after surgery. Postoperative weight loss follows almost
all bowel resections. Weight and strength are slowly
regained over a period of months.

Risks
Potential complications of this abdominal surgery
include:


excessive bleeding



surgical wound infection



incisional hernia (An organ projects through the
muscle wall that surrounds it. The hernia occurs
through the surgical scar.)



thrombophlebitis (inflammation and blood clot to
veins in the legs)
629

Bowel resection

I Bowel resection

Bowel training



pneumonia



pulmonary embolism (blood clot or air bubble in the
lungs’ blood supply)

KEY TERMS
Defecate—To pass feces (stool) out of the rectum
through the anus.
Diverticulitis—Infection of outpouchings in the
large bowel.

Normal results
Complete healing is expected without complications after bowel resection. The period of time
required for recovery from the surgery may vary
depending of the patient’s overall health status prior
to surgery.

Fecal impaction—Obstruction of the rectum by a
large mass of feces (stool).
Hiatal hernia—Part of the stomach displaced
through the diaphragm into the chest.

Abnormal results
The doctor should be made aware of any of the
following problems after surgery:


increased pain, swelling, redness, drainage, or bleeding in the surgical area



headache, muscle aches, dizziness, fever



increased abdominal pain or swelling, constipation, nausea or vomiting, rectal bleeding, or black, tarry stools

habits not only improve the quality of life, they help
prevent several common diseases–for example, diverticulitis and fecal impaction. Gall stones, appendicitis,
colon cancer, hiatal hernia, diabetes, and heart disease
have also been related to the quality of bowel movements and the foods that affect them.


One of the most common causes of constipation is
the laxative habit. Repeated artificial stimulation of
the bowels destroys their natural emptying reflex, so
that they will no longer move without artificial stimulants. The laxative habit begins innocently
enough with the correct belief that bowels should
move every day, however, laxatives will cause the
evacuation of several days worth of stool in a single
movement. Impatient for stool to reaccumulate for
the necessary few days, the patient takes another
laxative, and the cycle begins.



The other major cause of constipation is a diet with
insufficient bulk or roughage. The bowel works more
smoothly the more contents it has. Western diets of
highly refined foods have eliminated most of the
residue from food. The result is that most food is
absorbed, leaving little to pass through and be
excreted as feces.



Constipation occurs acutely with impaction–the presence in the rectum of a mass of feces too large to
pass. Fecal impaction is usually the result of poor
bowel habits, a diet with too little liquid and roughage, and inadequate physical activity.



Diarrhea, whether acute or chronic, can disrupt the
bowel’s normal rhythm and lead to irregularity.



Several diseases of the nervous system affect bowel
reflexes.

Resources
ORGANIZATIONS

United Ostomy Association, Inc. (UOA). 19772 MacArthur
Blvd., Suite 200, Irvine, CA 92612-2405. (800) 8260826. <http://www.uoa.org>.
Wound Ostomy and Continence Nurses Society. 1550 South
Coast Highway, Suite #201.

Kathleen D. Wright, RN

Bowel surgery with ostomy see Colostomy

I Bowel training
Definition
Bowel training helps to reestablish normal bowel
movements in persons who suffer from constipation,
diarrhea, incontinence, or irregularity. Healthy bowel
activity is considered one or two movements of moderate size every day.

Purpose
Many people for many reasons have irregular
bowel function. In some cases, the irregularity lasts
beyond the condition that caused it. The bowels by
themselves develop bad habits that can be retrained
with suitable exercises and education. Normal bowel
630

Description
Bowel training reestablishes the bowel’s normal
reflexes by repeating a routine until it becomes a habit.
GALE ENCYCLOPEDIA OF MEDICINE

After gaining the patient’s cooperation, the next
step is to optimize the diet. Healthy bowel movements
require ingestion of a large amount of liquids and bulk
foods. The patient should drink two to three quarts of
liquids every day, with liberal inclusion of prune juice
and perhaps coffee for their natural laxative effect. Bulk
comes from unrefined foods. Oat bran, wheat bran,
brown rice, green vegetables, apples, and pears are a
few examples of high residue foods. Many patients will
benefit from adding bulk preparations of psyllium.
Constipating foods like bananas and cheese should be
avoided until a natural rhythm is well established.
To assure that stools are soft enough to pass easily,
it is a good idea to add a pure stool softener like DOSS
(dioctyl sodium sulfosuccinate), two to four per day as
needed. DOSS also helps prevent impaction.
There is usually a time of day when bowel movements are more likely to occur. In anticipation of this
time, the patient should participate in activities that
stimulate a normal bowel movement. Walking, eating
unrefined foods, and drinking prune juice or coffee,
encourage natural evacuation. It is acceptable to use
lubricants such as glycerine suppositories or oil enemas at this time. For severe constipation, water enemas may be needed to initiate a movement.
It is also important for the patient to recognize the
urge to defecate and to respond right away to that
urge. The longer stool sits in the rectum, the more
water the rectum will absorb from it, making it harder
and more difficult to pass.

Normal results
With patience and diligence, normal bowel habits
and the health that comes with them will return in
most patients.
Resources
BOOKS

Barker, L. Randol, et al., eds. Principles of Ambulatory
Medicine. Baltimore: William & Wilkins, 1994.

J. Ricker Polsdorfer, MD

Braces see Immobilization
Brachytherapy see Radioactive implants
GALE ENCYCLOPEDIA OF MEDICINE

I Brain abscess
Definition
Brain abscess is a bacterial infection within the
brain.

Description
The brain is usually well insulated from infection
by bacteria, protected by the skull, the meninges (tissue layers surrounding the brain), the immune system,
and the highly regulated barrier between the bloodstream and the brain. Under certain circumstances,
however, bacteria can invade the brain and cause a
localized infection called an abscess. Brain abscess is
relatively rare, accounting for 1 in 10,000 hospital
admissions. Single abscess occurs in 75% of cases,
and the remainder of cases involve multiple abscesses.
If not treated, brain abscess is almost always fatal.

Causes and symptoms
One-half of all brain abscesses are caused by the
spread of bacteria from a nearby infection. Sources of
bacteria include:


middle ear infections (otitis media) or infections in the
bony spaces in front of the middle ear (mastoiditis)



sinus infections



an abscessed tooth.

Other sources of bacteria include lung infections,
abdominal infection, infection of the heart’s lining (endocarditis) penetrating heart wounds, and neurosurgery.
Acquired Immune Deficiency Syndrome (AIDS)
or the presence of another immune deficiency greatly
increases the risk of brain abscess. Approximately
25% of cases have no detectable cause of infection.
Brain abscess can be caused by a variety of organisms, many of them related to ear and sinus infections.
Many times brain abscess cases are caused by two or
more bacteria. In 30–60% of cases, the bacteria
combination includes streptococci, microorganisms
that can live without oxygen (anaerobes), and enterobacteria. A small number of cases are caused by
yeast, fungi, and single-cell organisms (protozoa).
The symptoms of brain abscess often develop
slowly, usually within a period of about two weeks.
The most common symptoms are:


headache



neurologic symptoms related to the specific part of
the brain that is infected
631

Brain abscess

Naturally the patient must be able and willing to
cooperate. Some patients are so convinced they need
daily laxatives that they are afraid to do without them.
It takes time for a changed diet to effect the bowels and
for the bowel to regain its normal rhythm. Trust and
patience are necessary.

Brain biopsy

KEY TERMS
Biopsy—The removal of a tissue sample for
examination.
Aspiration—Removal of fluid from a closed space
through a needle.



altered mental status



seizures

Diagnosis
Diagnosis of brain abscess is performed by using
a computed tomography scan (CT) or a magnetic
resonance imaging (MRI) scan to determine the site of
infection. Tissue removal (biopsy) is usually performed
as well. A biopsy is performed to determine the type of
bacterium involved. Biopsies can also be used to rule
out tumor or other noninfectious localized lesions,
which may look the same on the scans.
Other tests are performed to determine the source
of the infection. These tests include blood cultures,
x rays of the chest, and a physical exam of the ears,
sinuses, and teeth. A test for human immunodeficiency
virus (HIV) is usually also performed.

Treatment
Treatment for brain abscess begins with intravenous antibiotics, chosen to match the infecting bacterium if known, or to cover a wide spectrum of
possibilities if not. Treatment usually continues for
six to eight weeks.
Aspiration surgery is almost always done to drain
the abscess. In this procedure, a needle is guided to the
infected site by CT scan, and fluid is removed (aspirated) from the abscess. Aspiration may be repeated
several times until the bacteria are completely killed or
removed. Surgical removal of infected or dead tissue
may be needed in some cases. For patients with many
sites of infection, aspiration or surgical removal is not
done because of the increased difficulty and risk of the
procedure. For these patients, antibiotic therapy alone
is used. Steroid treatment is controversial, but may be
indicated in some cases.

survive have some residual neurological problems,
including seizures in many patients.
There are several reasons why patients with brain
abscess can have a poor prognosis. The illness may
not be diagnosed correctly or an accurate diagnosis
may take additional time. The patient may receive an
antibiotic that does not match the infecting organism. Sometimes the infection may not be limited to a
definite area in the brain, making diagnosis and treatment difficult. The small number of cases caused by
fungal infection may take additional time to diagnose. A patient may also have a poor prognosis
because there is more than one abscess, the location
of the abscess may be deep within the brain, or the
infection may have moved into many locations within
the brain. Severe complications can result from
brain abscess, including comma and brain rupture.
In 80-100% of cases involving brain rupture, the
patient dies.

Prevention
Brain abscess may be preventable by prompt and
aggressive treatment of the infections which give rise
to it, especially sinus and ear infections.
Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

Richard Robinson

Brain aneurysm see Cerebral aneurysm

I Brain biopsy
Definition
A brain biopsy is the removal of a small piece of
brain tissue for the diagnosis of abnormalities of the
brain, such as Alzheimer’s disease, tumors, infection,
or inflammation.

Purpose
Prognosis
Even with prompt treatment, brain abscess is fatal
in about 20% of cases. About half of those who
632

By examining the tissue sample under a microscope,
the biopsy sample provides doctors with the information
necessary to guide diagnosis and treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Alzheimer’s disease—A progressive, neurodegenerative disease characterized by loss of function
and death of nerve cells in several areas of the
brain, leading to loss of mental functions such as
memory and learning.
Computed axial tomography (CT)—Computed
axial tomography (CT) is a x-ray technique that
has the ability to image soft tissue, bone, and
blood vessels.
Cortex—The thin convoluted surface of the brain
comprised primarilyof cell bodies of neurons.
MRI—Magnetic resonance imaging is an imaging
technique that uses radiowaves, magnetic fields,
and computer analysis to visualize body tissue
and structures.
Stereotactic brain needle biopsy—In this procedure a computer uses information from a CT or MRI
to create a three-dimensional map of the operation
site to better guide the needle to perform the biopsy.

Precautions
Imaging of the brain is performed to determine
the precise positioning of the needle to enter the brain.

Description
When an abnormality of the brain is suspected,
Stereotactic (probing in three dimensions) brain needle biopsy is performed and guided precisely by a
computer system to avoid serious complications. A
small hole is drilled into the skull, and a needle is
inserted into the brain tissue guided by computerassisted imaging techniques (CT or MRI scans).
Historically, the patient’s head was held in a rigid
frame to direct the probe into the brain; however
since the early nineties, it has been possible to perform
these biopsies without the frame. Since the frame was
attached to the skull with screws, this advancement is
less invasive and better tolerated by the patient. The
doctor (pathologist) prepares the sample for analysis
and studies it further under a microscope.

Preparation
A CT or MRI brain scan is done to find the
position where the biopsy will be performed. Prior to
the biopsy, the patient is placed under general
anesthesia.
GALE ENCYCLOPEDIA OF MEDICINE

The patient is monitored in the recovery room for
several hours and is usually required to spend a few
days in the hospital since general anesthesia is required.

Risks
The procedure is invasive and includes risks
associated with anesthesia and surgery. Brain injury
may occur due to removal of brain tissue. The resulting scar, left on the brain has the potential to trigger
seizures.

Normal results
After examining the brain tissue directly, no
abnormalities are detected.

Abnormal results
Various brain abnormalities can be diagnosed
by microscopic analysis of the tissue sample. The
pathologist (a physician trained in how disease affects
the body’s tissues) looks for abnormal growth,
changes in cell membranes, and/or abnormal collections of cells. In Alzheimer’s disease, the cortex of the
brain contains abnormal collections of plaques. If
infection is suspected, the infectious organism can be
cultured from the tissue and identified. Classification
of tumors is also possible after biopsy.
Resources
ORGANIZATIONS

Alzheimer’s Association. 919 North Michigan Ave., Suite
1100 Chicago, IL 60611-1676.(800) 272-3900 <http://
www.alz.org>.
American Brain Tumor Association. 2720 River Road, Suite
146, Des Plaines, IL 60018-4110. (800) 886-2282.
<http://www.abta.org>.
National Institute of Neurological Disorders and Stroke,
NIH Neurological Institute. P.O. Box 5801 Bethesda,
MD 20824. (800) 352-9424. <http://www.ninds.nih.gov/index.htm>.

Bonny McClain, MS

Brain circulation scan see Transcranial
Doppler ultrasonography
Brain infection see Encephalitis
Brain injury see Head injury
Brain surgery see Craniotomy
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Brain biopsy

Aftercare

KEY TERMS

Brain tumor

I Brain tumor
Definition
A brain tumor is an abnormal growth of tissue in
the brain. Unlike other tumors, brain tumors spread
by local extension and rarely metastasize (spread)
outside the brain. A benign brain tumor is composed
of non-cancerous cells and does not metastasize
beyond the part of the brain where it originates. A
brain tumor is considered malignant if it contains
cancer cells, or if it is composed of harmless cells
located in an area where it suppresses one or more
vital functions.

Description
Each year, more than 17,000 brain tumors are
diagnosed in the United States. About half of all primary brain tumors are benign, but in life-threatening
locations. The rest are malignant and invasive.
Benign brain tumors

A scan of a brain with a tumor located in the central right
portion of the brain. (Illustration by Argosy Inc.)

Benign brain tumors, composed of harmless cells,
have clearly defined borders, can usually be completely removed, and are unlikely to recur. Benign brain
tumors do not infiltrate nearby tissues but can cause
severe pain, permanent brain damage, and death.
Benign brain tumors sometimes become malignant.

KEY TERMS
Central nervous system (CNS)—The division of the
nervous system that consists of the brain and spinal
cord.
Cerebrospinal fluid (CSF)—Clear liquid that fills
brain cavities and protects the brain and spinal
cord.

Malignant brain tumors
Malignant brain tumors do not have distinct borders. They tend to grow rapidly, increasing pressure
within the brain (IICP) and can spread in the brain or
spinal cord beyond the point where they originate. It is
highly unusual for malignant brain tumors to spread
beyond the central nervous system (CNS).

Gamma knife—High-dose radiation treatment for
intracranial tumors.
Intracranial—Located within or on the surface of
the brain.

Primary brain tumors
Primary brain tumors originate in the brain. They
represent about 1% of all cancers and 2.5% of all
cancer deaths.
Metastatic or secondary brain tumors
Approximately 25% of all cancer patients develop
secondary or metastatic brain tumors when cancer
cells spread from another part of the body to the
brain. Secondary brain tumors are most apt to occur
in patients who have:


breast cancer.



colon cancer.

634



kidney cancer.



lung cancer.



melanoma (cancer) of the skin. These metastatic
brain tumors can develop on any part of the brain
or spinal cord.



cancer within the nasal passages and/or throat that
follow the nerve pathways into the skull, and metastasize to the brain.
GALE ENCYCLOPEDIA OF MEDICINE

Brain tumors can develop at any age, but are
most common in children between the ages of 3-12,
and in adults aged 55-65. Primary brain cancer is the
second most common cause of cancer death between
birth and the age of 34, and the fourth most common
cause of cancer death in men aged 35-54. Primary
tumors of the brain and central nervous system are
often associated with HIV infection. Men and caucasians have a higher risk of developing brain
tumors. Other risk factors being studied include children with a history of previous radiation treatment
to the head for cancer; parents with certain cancers
(nervous system, salivary gland, colon); having an
older father; having well-educated parents; occupational exposure to vinyl chloride, lead, and pesticides; history of epilepsy; history of certain genetic
conditions (tuberous sclerosis, neurofibromatosis, von
Hippel Lindau, familial polyposis, Osler-WeberRendu, Li-Fraumeni).
Naming and grading brain tumors
The name of a brain tumor describes where it
originates, how it grows, and what kind of cells it
contains. A tumor in an adult is also graded or staged
according to:


how malignant it is



how rapidly it is growing and how likely it is to
invade other tissues



how closely its cells resemble normal cells. (The more
abnormal a tumor cell looks, the faster it is likely to
grow)

Low-grade brain tumors usually have welldefined borders. Some low-grade brain tumors form
or are enclosed (encapsulated) in cysts. Low-grade
brain tumors grow slowly, if at all. They may spread
throughout the brain, but rarely metastasize to other
parts of the body.
Mid-grade and high-grade tumors grow more
rapidly than low-grade tumors. Described as ‘‘truly
malignant,’’ these tumors usually infiltrate healthy
tissue. The growth pattern makes it difficult to remove
the entire tumor, and these tumors recur more often
than low-grade tumors.
A single brain tumor can contain several different
types of cells. The tumor’s grade is determined by the
highest-grade (most malignant) cell detected under a
microscope, even if most of the cells in the tumor are
less malignant. An infiltrating tumor is a tumor of any
grade that grows into surrounding tissue.
GALE ENCYCLOPEDIA OF MEDICINE

Types of brain tumors
Glioma is the term used to refer to the most prevalent primary brain tumors. Gliomas arise from glial
tissue, which supports and nourishes cells that send
messages from the brain to other parts of the body.
These tumors may be either malignant or benign.
Astrocytomas, ependymomas, and mixed gliomas are
three of the most common gliomas.
ASTROCYTOMAS. Named for the star-like shape of
their cells, astrocytomas can develop on any part of
the brain or spinal cord. Non-infiltrating astrocytomas grow slowly, and rarely spread to nearby tissue.
Mild-to-moderately anaplastic astrocytomas with
well-differentiated borders do not grow as slowly as
non-infiltrating astrocytomas, and they do spread to
surrounding tissues.

Anaplastic astrocytomas, which are also called
Grade III astrocytomas, look more abnormal and
grow more rapidly than non-infiltrating or mild-tomoderately anaplastic tumors.
Grade IV astrocytomas are also called glioblastoma multiforme (GBM) tumors. Accounting for 30%
of all primary brain tumors, GBMs are the most common brain tumors in middle-aged adults. GBMs are
the most malignant of all brain tumors. Because they
contain a greater mixture of cells than any other brain
tumor, they are the most difficult to treat.
EPENDYMOMAS. Also called ependymal tumors,
ependymomas account for 9% of all gliomas, and
5% of all intracranial tumors. These tumors, which
are most common in children and adolescents, begin in
the very thin membranes that help form cerebrospinal
fluid (CSF) and line the brain cavities (ventricles) that
contain it.

Ependymomas are usually benign, have welldifferentiated borders, resemble normal cells, and
grow very slowly. The cells of anaplastic (malignant)
ependymomas look abnormal and grow more rapidly
than the cells of benign tumors.
MIXED GLIOMAS. These heterogeneous tumors contain elements of astrocytomas and ependymomas and/
or oligodendrogliomas. These are rare tumors that
usually occur in middle-aged adults, grow slowly, and
do not usually spread beyond the part of the brain where
they originate. Mixed gliomas behave like tumors composed of the highest-grade cells they contain.

Non-glial brain tumors
The most common brain tumors that do not
develop from glial cells are medulloblastomas, meningiomas, and Schwannomas.
635

Brain tumor

Who gets brain tumors

Brain tumor

MEDULLOBLASTOMAS. Scientists once thought
medulloblastomas (MDLs) developed from glial
cells. These fast-growing, malignant tumors are now
believed to originate in developing cells not normally
present in the body after birth. They are sometimes
called primitive neurodectal tumors (PNET).

chemicals have a greater-than-average risk of developing them. There is no evidence that head injury causes
brain tumors, but researchers are trying to determine
the relationship, if any, between brain tumors and
viruses, family history, and long-term exposure to
electromagnetic fields.

MDL tumors are most common in children and
are more common in boys than in girls. Only 30% of
MDL tumors occur in adults. MDL tumors usually
originate in the cerebellum (the part of the brain that
controls coordination and some muscle activity), and
are often carried to other parts of the brain by cerebrospinal fluid. MDL tumors rarely metastasize
beyond the brain and spinal cord.

Symptoms do not usually appear until the tumor
grows large enough to displace, damage, or destroy
delicate brain tissue. When that happens, the patient
may experience:

MENINGIOMAS. Meningiomas, which represent
more than 20% of all primary brain tumors, originate in
the membranes that enclose the brain and spinal cord
(meninges). These tumors are usually benign and most
often occur in women aged 30-50 years old. Meningiomas
grow so slowly that the brain can sometimes become
accustomed to their presence. Meningiomas compress,
rather than invade, brain tissue and may grow to be
quite large before any symptoms appear.
SCHWANNOMAS. Schwannomas originate in the
Schwann cells. These cells produce myelin, material
that protects the acoustic nerve, which controls hearing. These benign tumors are twice as common in
women as in men, and are most often diagnosed in
patients between the ages 30-60.

Schwannomas grow very slowly, and many people
adapt to the slight hearing loss and balance problems
that are the tumors’ earliest symptoms. A pear-shaped
Schwannoma can cause sudden or gradual loss of hearing in an ear. As the tumor progresses, it can press on
the nerves that control movement and feeling in the
face, and cause headaches and facial numbness or
tingling. The patient may have trouble walking, swallowing, or controlling eye movements, and the sense of
taste can be affected. A Schwannoma that grows large
enough to press on the brainstem can be deadly.
tumors
that occur in children are described as supratentorial
(in the upper part of the brain) or infratentorial (in
the lowest part of the brain). Astrocytomas and ependymomas are common supratentorial tumors.
Infratentorial tumors include medulloblastomas,
astrocytomas, and ependymomas.
CHILDHOOD

BRAIN

TUMORS. Brain

Causes and symptoms
The cause of primary brain tumors is unknown,
but people who work with rubber and certain
636



headaches that become increasingly painful and are
most painful when lying down



nausea and vomiting or sudden attacks of vomiting
not accompanied by nausea



seizures



dizziness, loss of coordination or balance



personality changes



sudden loss of vision



memory loss



speech problems



sensory changes



mental impairment



weakness or paralysis on one side of the body

A doctor should be notified whenever a patient
experiences one or more of the symptoms.

Diagnosis
Although brain tumor symptoms resemble those
of many other illnesses, the presence of a brain tumor
may be indicated by:


persistent headaches with vomiting or convulsions



progressive deterioration of sight, speech, hearing,
touch; or deterioration in the ability to use an arm,
hand, foot, or leg

When a patient experiences one or more of the
above symptoms, a primary care physician will perform a complete physical examination, take a detailed
medical history, and conduct a basic neurologic examination to evaluate:


balance and coordination



abstract thinking and memory



eye movements



hearing, touch, and sense of smell



reflexes
GALE ENCYCLOPEDIA OF MEDICINE

control of facial muscles and movements of the head
and tongue



the patient’s health history and current medical
status



awareness



the wishes of the patient and his family

If the results of these examinations suggest a
patient may have a brain tumor, a neurologist recommends some or all of these additional diagnostic tests:


computed tomography scan (CT scan) to reveal
brain abnormalities



magnetic resonance imaging (MRI) to detect tumors
beneath the bones of the skull



complex imaging techniques such as Positron emission tomography (PET scan), Single photon emission
tomography (SPECT scan)

Surgery
Surgery is the treatment of choice for accessible
brain tumors, which can be removed without causing
serious neurologic damage. The procedure most often
performed is a craniotomy, but the goals of any type of
brain tumor surgery include:


removing as much of the tumor as possible (called
debulking the tumor)



removing tumor tissue for microscopic analysis



electroencephalography (EEG) to measure electrical
activity in the brain



allowing neurosurgeons to see exactly how the tumor
is situated and how it is growing



magnetoencephalography (MEG scan) to measure
the magnetic fields produced by nerve cells and
their electric currents



creating an entry channel for chemotherapy drugs
and forms of radiation that are implanted in the
brain



x rays to reveal any distortion in the bones of the
skull



angiography to outline a tumor and the blood vessels
that lead to it

Depending on the type of brain tumor, its location, and its size, a number of different techniques may
be used to surgically remove it. Surgical techniques
include:



a brain scan to identify and record the location of
abnormal cells in the brain









radionuclide brain scintigraphy to view the capillaries feeding the tumor after highlighting them
with a radioactive substance
myelography (x ray of the spine) to detect a spinal
cord tumor
a lumbar puncture (spinal tap) to obtain spinal fluid,
which may contain tumor cells.
digital holography to view a complete three-dimensional map of the tumor and surrounding brain
structures

Interpreting these images and results of laboratory analysis allows neurologists to determine whether
a tumor is present, but microscopic examination of
tumor tissue (biopsy) is the only way to identify the
kind of cells it contains.

Treatment
Brain tumors are treated by multidisciplinary
teams of highly skilled specialists whose decisions are
based on:


results of diagnostic tests



tumor size, position, and growth pattern

GALE ENCYCLOPEDIA OF MEDICINE



classic operation



laser microsurgery (uses high temperatures to vaporize tumor cells



ultrasonic aspiration (uses ultrasound waves to
break up the tumor into smaller bits which can be
‘‘vacuumed’’ out

Before undergoing brain surgery, patients are
often given:


steroids to reduce swelling of brain tissue



anticonvulsant medications to prevent or control
seizures



radiation treatments to reduce tumor size

Patients whose benign brain tumors can be completely removed may not require any additional treatment, but periodic physical and neurologic
examinations and CT or MRI scans are sometimes
recommended to determine whether the tumor has
returned. Because surgeons cannot be sure that every
bit of an infiltrating or metastasizing tumor has been
removed, radiation and chemotherapy are used to
eradicate cells that may have escaped the scalpel.
If a tumor cannot be completely removed, removing a portion of it (debulking) can alleviate the
patient’s symptoms, enhance the sense of well-being,
and increase the effectiveness of other treatments.
637

Brain tumor



Brain tumor

Radiation therapy
External radiotherapy, generally delivered on an
outpatient basis, directs radiation to the tumor and the
area around it. Implant radiation therapy involves
placing tiny pieces of radioactive material in the
brain. Left in place permanently, or for a short time,
these radioactive pellets release measured doses of
radiation each day. This technique is called brachytherapy. Patients are usually hospitalized during
the several days the pellets are most active.
Stereoactic radiosurgery involves fitting the
patient with a frame to stabilize the head, using imaging
techniques to determine the exact location of tumor
cells, and using a sophisticated instrument to administer radiation precisely to that point. Instruments used
for delivery of radiation include the gamma knife,
adapted linear accelerator (LINAC), and cyclotron.
A variety of drugs may also be given during radiation therapy, to protect brain cells from the effects of
radiation (radioprotective drugs), to increase the sensitivity of tumor cells to radiation (radiosensitizers), or
to boost radiation’s effects (radioenhancers).
Chemotherapy
One or more cancer-killing drugs may be taken by
mouth or injected into a blood vessel, muscle, or the
cerebrospinal fluid. Chemotherapy may be used with
radiation and surgery as part of a patient’s initial
treatment, or used alone to treat tumors that recur in
the same place or in another part of the body. The
usual chemotherapy regimen for a brain tumor is a
combination approach, most commonly using procarbazine, CCNU, and vincristine.

When a young child has a brain tumor, chemotherapy is often used to eliminate or delay the
need for radiation.
Other treatments
If a brain tumor cannot be cured, treatment is
designed to make the patient as comfortable as possible and preserve as much of his neurologic functioning
as possible. The patient’s doctor may prescribe:


analgesics to relieve pain



anticancer drugs to limit tumor growth



anticonvulsants to control seizures



steroids to reduce swelling of brain tissue
Potential therapies

Scientists are studying ways to empower chemotherapy drugs to penetrate the blood-brain barrier
(which protects the CNS by separating the brain
from blood circulating throughout the body), and
attack cancer cells that have infiltrated tissue
inside it. Agents under investigation include both
mannitol and substances called receptor-mediated
permeabilizers
Brain tumor researchers are also investigating:


Less invasive surgical procedures.



Monoclonal antibodies, which pair antibodies with
radioactive substances. The antibodies are directed
to find and attach to tumor cells, at which time the
radioactive substance kills the tumor cell.



Interleukin and interferon, which are substances produced naturally by the human immune system which
seem to kill tumor cells. Scientists seek to produce
these substances in the laboratory and incorporate
their use in brain tumor treatment.



T-lymphocytes, which are also produced normally
by the human immune system, and are being used
to inject directly into the tumor location during surgery and to infuse into the bloodstream after surgery,
in the hopes that they will boost the immune system’s
ability to fight tumor cells.



Tumor vaccines, which use elements of tumor cells to
stimulate the patient’s immune system.



Methods of incorporating chemotherapy drugs into
tumor cells to reduce the need for radiation.



Laboratory techniques that enable physicians to
select the chemotherapy drugs most likely to kill
particular types of tumors.

New methods of delivering chemotherapy are
being used as well. These include:


interstitial chemotherapy is performed at the time of
surgery. A chemotherapy-soaked wafer is placed in
the cavity left after tumor removal.



Intrathecal chemotherapy instills the medications
right into the spinal fluid.



Intraarterial chemotherapy uses tiny catheter tubes
to delivery high-dose chemotherapy directly into the
arteries of the brain.



Potentially toxic chemotherapy drugs can be
wrapped in special biologic envelopes called liposomes, to allow the drugs to be delivered to the
tumor without adversely affecting other healthy tissues along the way.



Electrochemotherapy uses electric voltage to transport chemotherapy agents into the brain.

638

GALE ENCYCLOPEDIA OF MEDICINE

Gene therapy in which genetically engineered material is transported to tumor cells by viruses that infect
tumor cells and convert them to normal cells, stop
their growth, or kill them.

Alternative treatment
Alternative treatments have not been shown to
cure brain tumors and should never be substituted
for conventional therapy. However, complementary
therapies (used with, not instead of, standard treatments) can help some patients cope with the stress of
their illness and side effects of their treatment.
Massage, meditation, and reflexology help some
patients relax; while yoga is said to soothe the body,
spirit, and mind. Hydrotherapy uses ice, liquid, and
steam to improve circulation and relieve pain.
Therapeutic touch practitioners say they can relieve
pain and other symptoms by moving their hands in
slow, rhythmic motions several inches above the
patient’s body.
Botanical therapies, homeopathic treatment, traditional Chinese medicine treatments, nutritional
focuses on diet and supplements, and detoxification
can also be incorporated as complementary therapies.

Prognosis
The patient’s prognosis depends on where the
tumor is located, what type of cells it contains, the
size of the tumor, and the effect its already had on
adjacent brain structures. A patient whose tumor is
discovered early and removed completely may make a
full recovery, but the surgery itself can harm or destroy
normal brain tissue and cause:


problems with thought, speech, and coordination



seizures



weakness



personality changes.

Hospices provide a supportive environment and help
patients manage pain and remain comfortable.
Consequences of radiation therapy
Cells killed by radiation can cluster in the brain,
resembling tumors. They can cause headaches, seizures, and memory loss. Children treated with radiation may lose some of their eyesight and develop
learning problems. Radiation damage to the pituitary
gland can hinder normal growth and development.
Consequences of chemotherapy
Some drugs used to treat brain tumors can cause
kidney damage and temporary or permanent tingling
in the fingers and ringing in the ears.
Inoperable tumors
Brain tumors that cannot be removed may cause
irreversible brain damage and death.

Prevention
The cause of primary brain tumors has not been
determined, so there is no known way to prevent
them.
The best way to prevent secondary or metastatic brain tumors is to eliminate such risk
factors as:


poor nutrition and a low-fiber diet; since these contribute to development of intestinal cancers



smoking, which causes lung cancer



excessive use of alcohol, which is associated with
liver cancer



excessive exposure to the sun, which can cause melanoma (a deadly form of skin cancer).

Monthly self-examinations of the breasts and testicles can detect breast and testicular cancer at their
earliest, most curable stages.

Although these post-operative problems may
initially be more severe than the symptoms produced
by the tumor, they will probably diminish or disappear
in time.

ORGANIZATIONS

Occupational therapy can teach patients and their
families new ways to approach daily tasks. Physical
therapy can benefit patients who have difficulty keeping their balance, expressing their thoughts, speaking,
or swallowing. Children may need special tutors before
and after returning to school. For patients who have
incurable brain tumors, hospice care may be available.

American Brain Tumor Association. 2770 River Road, Des
Plaines, IL 60018. (847) 827-9918, (800) 886-2289.
<http:/www.abta.org>.
Brain Tumor Foundation for Children, Inc. 2231 Perimeter
Park Drive, Suite 9, Atlanta, GA 30341. (404) 454-5554.
Brain Tumor Information Services. Box 405, Room J341,
University of Chicago Hospitals, 5841 S. Maryland
Avenue, Chicago, IL 60637. (312) 684-1400.

GALE ENCYCLOPEDIA OF MEDICINE

Resources

639

Brain tumor



Breast biopsy

MedHelp International. 6300 N. Wickham, Suite 130, Box
188, Melbourne, FL 32940. (407) 253-9048. <http://
www.medhlp.netusa.net>.
National Brain Tumor Foundation. 785 Market Street,
#1600, San Francisco, CA 94103. <http://
www.oncolink.penn.edu/psychosocial>.

KEY TERMS
Fine needle aspiration biopsy—A procedure using
a thin needle to remove fluid and cells from a lump
in the breast.
Large core needle biopsy—A procedure using a
thicker needle to remove a core of tissue, about
the size of a grain of rice, from the breast.

OTHER

Adult Brain Tumor. May 2001. <http://cancernet.nci.nih.
gov/clinpdq/pif/Adult_brain_tumor_Patient.html>.
Brain Tumor, Primary. Nidus Information Services, Well
Connected, 2001.
‘‘Brain Tumors,’’ Abeloff: Clinical Oncology, 2nd ed.
Churchill Livingstone, Inc., 2000.
‘‘Brain Tumors,’’ Goldman: Cecil Textbook of Medicine.
21st ed. W. B. Saunders Company, 2000.
Childhood Brain Tumor. May 2001. <http://cancernet.
nci.nih.gov/clinpdq/pif/
Childhood_brain_tumor_Patient.html>.
Question: What is a Gamma Knife? April 13, 2001. <http://
oncolink.upenn.edu/specialty/med_phys/
gamma.html>.

felt, how well it can be seen on mammogram or ultrasound, and how suspicious it feels or appears.
Specialized equipment is needed for different types of
biopsy and availability may vary. Generally, needle
biopsy is less invasive than surgical biopsy. It is appropriate for most, but not all situations. However, some
surgeons feel it is far less accurate.

Description

Rosalyn Carson-DeWitt, MD

Surgical biopsy

Breast-feeding see Lactation

I Breast biopsy
Definition
A breast biopsy is removal of breast tissue for
examination by a pathologist. This can be accomplished
surgically, or by withdrawing tissue through a needle.

Purpose
A biopsy is recommended when a significant
abnormality is found, either on physical examination
and/or by an imaging test. Examples of abnormality
can include a breast lump felt during physical self
examination or tissue changes noticed from a mammogram test. Before a biopsy is performed, it is important to make sure that the threat of cancer cannot be
disproved or ruled out by a simpler, less invasive
examination. A lump may be obviously harmless
when examined by ultrasound. If this is not decisive,
the presence of cancer or a variety of benign breast
conditions can be determined using a biopsy.

Precautions
The type of biopsy recommended should be considered. This will depend on whether the area can be
640

If an abnormality is not felt during a self examination, there are signs that indicate the need for medical attention. These include:


severe breast pain



changes in the size of a breast or the nipple



changes in the shape of both breast or nipple



pitting, dumpling or redness of the breast skin



nipple redness, irritation, or inversion



changes in the pattern of veins visible on the surface
of the breast



some types of nipple discharge

If the abnormality is not felt, a needle localization
must be done before the actual surgery. After local
anesthetic is administered, a fine wire is placed in the
area of concern. Either x ray or ultrasound guidance is
used. The patient is awake and usually sitting up.
There are two types of breast biopsy considered
here, excisional and incisional. An excisional biopsy is a
surgical procedure, where the entire area of concern
and some surrounding tissue is removed. It is usually
done as an outpatient procedure, in a hospital or free
standing surgery center. The patient may be awake, and
is sometimes given medication to make her drowsy.
The area to be operated on is numbed with local
anesthetic. Infrequently, general anesthesia is used.
An excisional biopsy itself usually takes under one
hour. The total amount of time spent at the facility
GALE ENCYCLOPEDIA OF MEDICINE

Breast biopsy

Subcutaneous
fatty tissue

Areola

Tumor

Lactiferous
duct
Tumor

Lobule of gland
Fine needle aspiration biopsy

Excisional biopsy

A fine needle aspiration biopsy uses a very thin needle to withdraw fluid and cells from the breast to be examined. An excisional
biopsy is a surgical procedure in which the entire area of concern and some surrounding tissue is removed for analysis.
(Illustration by Electronic Illustrators Group.)

depends on the type of anesthesia used, whether a
needle localization was done, and the extent of the
surgery.
If a mass is very large, an incisional biopsy may be
performed. In this case only a portion of the area is
removed and sent for analysis. The procedure is the
same as an excisional biopsy in other respects.
Needle biopsy
A needle biopsy removes part of the suspicious
area for examination. There are two types, aspiration
biopsy (using a fine needle), and large core needle
biopsy. Either of these may be called a percutaneous
needle biopsy. Percutaneous refers to a procedure
done through the skin.
A fine needle aspiration biopsy uses a very thin
needle to withdraw fluid and cells that can be studied.
It can be done in a doctor’s office, clinic, or hospital.
Local anesthetic may be used, but is sometimes withheld, as it may be more painful than the biopsy needle.
The area to place the needle may be located by touch.
No specialized equipment is needed. However, using
ultrasound guidance enables the physician to feel and
see the lesion at the same time. The actual withdrawing
of fluid and cells can be visualized as it occurs. This helps
ensure that the specimen is taken from the right place.
A large core needle biopsy uses a larger diameter
needle to remove small pieces of tissue, about the size
of a grain of rice. It can be done in a clinic or hospital
that has the appropriate facilities. Local anesthetic is
GALE ENCYCLOPEDIA OF MEDICINE

routinely used. Ultrasound or x ray is used for guidance of a large core needle biopsy.
If the suspicious area is seen best with x ray, a
stereotactic device is used. This means that x rays are
taken from several angles. This information is fed into
a computer, which analyzes the data and guides the
needle to the correct place. The patient may be sitting
up, or she may be lying on her stomach, with her breast
positioned through an opening in the table. The breast
is held firmly, but comfortably between a plastic paddle and a metal plate, similar to those used for mammograms (a set of x rays taken of the front and side of
the breast). X rays may be taken before, during, and
after the tissue is drawn into the needle, to confirm
that the correct spot is biopsied. This procedure may
also be referred to as a stereotactic core biopsy, or a
mammotomy.
Ultrasound is used to guide needle placement for
some lesions. The patient lies on her back or side. After
the area is numbed, sterile gel is applied. The physician
places a transducer, an instrument about the size of an
electric shaver, over the skin. This produces an image
from the reflection of sound waves. A special needle,
usually in a spring loaded device, is used to obtain the
tissue. The procedure is observed on a monitor as it is
happening.

Preparation
A surgical breast biopsy may require the patient to
have nothing to eat or drink for a period of time before
641

Breast cancer

the operation. This will typically be from midnight the
night before, if general anesthesia is planned. No food
restrictions are necessary for needle biopsy. It is advisable to eat lightly before the procedure. This is especially important if the patient will be lying on her
stomach for a stereotactic biopsy.

Aftercare
After a surgical biopsy, the incision will be closed
with stitches, and covered with a bandage. The bandage
can usually be removed in one or two days. Stitches
are taken out approximately one week afterward.
Depending on the extent of the operation, normal activities can be resumed in approximately one to three days.
Vigorous exercise may be limited for one to three weeks.
The skin opening for a needle biopsy is minimal.
It may be closed with thin, clear tape, called a steri strip,
or covered with a bandaid and a small gauze bandage.
The patient can return to her usual routine immediately
after the biopsy. Strenuous activity or heavy lifting is
not recommended for 24 hours. Any bandages can be
removed one or two days after the biopsy.

Abnormal results
An abnormal pathology report indicates a cancer
is present. If a fine needle aspiration biopsy was performed, the pathologist has viewed individual cells
under a microscope to see if they appear cancerous.
Large core needle biopsy and surgical biopsy will be
able to give more information. This includes the type
of cancer, whether it has invaded surrounding tissue,
and how likely it is to spread quickly. There are some
conditions which are not malignant but indicate high
risk for future development of breast cancer. If these
are identified, more frequent monitoring of the area
may be recommended.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Ellen S. Weber, MSN

Risks
Infection is always a possibility when the skin is
broken, although this rarely occurs. Redness, swelling,
or severe pain at the biopsy site would indicate a
possible infection. Another possible consequence of a
breast biopsy is a hematoma. This is a collection of
blood at the biopsy site. It is usually absorbed naturally by the body. If it is very large and uncomfortable,
it may need to be drained. A surgical breast biopsy
may produce a visible scar on the breast. Sometimes
this may make future mammograms harder to interpret accurately.
A false negative pathology report is another risk.
This means that no cancer was found when a cancer
was present. The incidence of this varies with the
biopsy technique. In general, fine needle aspiration
biopsies have the highest rate of false negative results,
but there may be variation in results between facilities.

Normal results
A normal pathology report indicates no malignancy is present. The tissue sample may be further
classified as a benign breast condition, such as tumor
of the breast (fibroadenoma) or connective tissue that
resembles fiber (fibrosis). Studies have demonstrated
that approximately 80% of all breast biopsies result in
a benign pathology report.
642

I Breast cancer
Definition
Breast cancer is caused by the development of
malignant cells in the breast. The malignant cells
originate in the lining of the milk glands or ducts of
the breast (ductal epithelium), defining this malignancy as a cancer. Cancer cells are characterized by
uncontrolled division leading to abnormal growth
and the ability of these cells to invade normal tissue
locally or to spread throughout the body, in a process
called metastasis.

Description
Breast cancer arises in the milk-producing
glands of the breast tissue. Groups of glands in
normal breast tissue are called lobules. The products
of these glands are secreted into a ductal system that
leads to the nipple. Depending on where in the
glandular or ductal unit of the breast the cancer
arises, it will develop certain characteristics that
are used to sub-classify breast cancer into types.
The pathologist will denote the subtype at the time of
evaluation with the microscope. Ductal carcinoma
GALE ENCYCLOPEDIA OF MEDICINE

Breast cancer

A breast cancer cell. (Phototake NYC. Reproduced by
permission.)

begins in the ducts, lobular carcinoma has a pattern
involving the lobules or glands. The more important
classification is related to the evaluated tumor’s capability to invade, as this characteristic defines the
disease as a true cancer. The stage before invasive
cancer is called in situ, meaning that the early malignancy has not yet become capable of invasion. Thus,
ductal carcinoma in situ is considered a minimal
breast cancer.

Mammogram indicating a tumor in the center of the breast.
(Chris Bjornberg, Photo Researchers. Reproduced by
permission.)

How breast cancer spreads
The primary tumor begins in the breast itself but
once it becomes invasive, it may progress beyond the
breast to the regional lymph nodes or travel (metastasize) to other organ systems in the body and become
systemic in nature. Lymph is the clear, protein-rich
fluid that bathes the cells throughout the body.
Lymph will work its way back to the bloodstream via
small channels known as lymphatics. Along the way,
the lymph is filtered through cellular stations known
as nodes, thus they are called lymph nodes. Nearly all
organs in the body have a primary lymph node group
filtering fluid that comes from that organ. In the
breast, the primary lymph nodes are under the armpit,
or axilla. Classically, the primary tumor begins in the
breast and the first place to which it is likely to spread
is the regional lymph nodes. Cancer, as it invades in
its place of origin, may also work its way into blood
vessels. If cancer gets into the blood vessels, the blood
GALE ENCYCLOPEDIA OF MEDICINE

vessels provide yet another route for the cancer to
spread to other organs of the body.
Breast cancer follows this classic progression
though it often becomes systemic or widespread early
in the course of the disease. By the time one can feel a
lump in the breast it is often 0.4 inches, or one centimeter, in size and contains roughly a million cells. It is
estimated that a tumor of this size may take one to five
years to develop. During that time, the cancer may
metastasize, or spread by lymphatics or blood to areas
elsewhere in the body.
When primary breast cancer spreads, it may first
go to the axillary nodes. If this occurs, regional metastasis exists. If it proceeds elsewhere either by lymphatic
or blood-borne spread, the patient develops systemic
metastasis that may involve a number of other organs
in the body. Favorite sites of systemic involvement for
breast cancer are the lung, bones, liver, and the skin
643

Breast cancer

KEY TERMS
Adjuvant therapy—Treatment involving radiation,
chemotherapy (drug treatment), or hormone therapy, or a combination of all three given after the
primary treatment for the possibility of residual
microscopic disease.
Aneuploid—An abnormal number of chromosomes in a cell.
Aspiration biopsy—The removal of cells in fluid or
tissue from a mass or cyst using a needle for microscopic examination and diagnosis.

50% 15%

18%

11% 6%

1/

This illustration shows the frequency of breast cancer developing in the four quadrants of the breast and the nipple.
(Illustration by Electronic Illustrators Group.)

and soft tissue. As it turns out, the presence of, and the
actual number of, regional lymph nodes containing
cancer remains the single best indicator of whether or
not the cancer has become widely metastatic. Because
tests to discover metastasis in other organs may not be
sensitive enough to reveal minute deposits, the evaluation of the axilla for regional metastasis becomes very
important in making treatment decisions for this
disease.
If breast cancer spreads to other major organs of
the body, its presence will compromise the function of
those organs. Death is the result of extreme compromise of vital organ function.

Benign—Not malignant, noncancerous.
Biopsy—A procedure in which suspicious tissue
is removed and examined by a pathologist for cancer
or other disease. For breast biopsies, the tissue may
be obtained by open surgery, or through a needle.
Estrogen-receptor assay—A test to see if a breast
cancer needs estrogen to grow.
Hormones—Chemicals produced by glands in the
body that circulate in the blood and control the
actions of cells and organs. Estrogens are hormones
that affect breast cancer growth.
Hormone therapy—Treating cancers by changing
the hormone balance of the body, instead of by
using cell-killing drugs.
Lumpectomy—A surgical procedure in which only
the cancerous tumor in the breast is removed,
together with a rim of normal tissue.
Lymph nodes—Small, bean-shaped masses of tissue scattered along the lymphatic system that act as
filters and immune monitors, removing fluids, bacteria, or cancer cells that travel through the lymph
system. Breast cancer cells in the lymph nodes
under the arm or in the chest are a sign that the
cancer has spread, and that it might recur.
Malignant—Cancerous.
Mammography—X-ray imaging of the breast that
can often detect lesions in the tissue too small or too
deep to be felt.
Oncogene—A gene that has to do with regulation of
cancer growth. An abnormality can produce cancer.

Demographics
Every woman is at risk for breast cancer. If she
lives to be 85, there is a one out of nine chance that she
will develop the condition sometime during her life. As
a woman ages, her risk of developing breast cancer
rises dramatically regardless of her family history. The
644

breast cancer risk of a 25-year-old woman is only one
out of 19,608; by age 45, it is one in 93. In fact, less
than 5% of cases are discovered before age 35 and
the majority of all breast cancers are found in women
over age 50.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
There are a number of risk factors for the development of breast cancer, including:


family history of breast cancer in mother or sister



early onset of menstruation and late menopause



reproductive history: women who had no children or
have children after age 30 and women who have
never breastfed have increased risk



history of abnormal breast biopsies

Though these are recognized risk factors, it is
important to note that more than 70% of women
who get breast cancer have no known risk factors.
Having several risk factors may boost a woman’s
chances of developing breast cancer, but the interplay
of predisposing factors is complex. In addition to
those accepted factors listed above, some studies suggest that high-fat diets, obesity, or the use of alcohol
may contribute to the risk profile. Another factor that
contributes to a woman’s risk profile is hormone
replacement therapy (HRT).
HRT provides significant relief of menopausal
symptoms, prevention of osteoporosis, and possibly
protection from cardiovascular disease and stroke.
While physicians have long known a small increased
risk for breast cancer was linked to use of HRT, a
landmark study released in 2003 proved the risk was
greater than thought. The Women’s Health Initiative
found that even relatively short-term use of estrogen
plus progestin is associated with increased risk of
breast cancer, diagnosis at a more advanced stage of
the disease, and a higher number of abnormal mammograms. The longer a woman used HRT, the more
her risk increased.
Of all the risk factors listed above, family history
is the most important. In The Biological Basis of
Cancer, the authors estimate that about half of all
familial breast cancer cases (families in which there is
a high breast cancer frequency) have mutations affecting the genes BRCA-1 or BRCA-2. In 2003, scientists
discovered a third gene called EMSY. However, breast
cancer due to heredity is only a small proportion of
breast cancer cases; only 5%–10% of all breast cancer
GALE ENCYCLOPEDIA OF MEDICINE

cases will be women who inherited a susceptibility
through their genes. Nevertheless, when the family
history is strong for development of breast cancer, a
woman’s risk is increased.
Not all lumps detected in the breast are cancerous.
Fibrocystic changes in the breast are extremely common. Also known as fibrocystic condition of the breast,
fibrocystic changes are a leading cause of noncancerous lumps in the breast. Fibrocystic changes
also cause symptoms of pain, swelling, or discharge
and may become evident to the patient or physician as
a lump that is either solid or filled with fluid. Complete
diagnostic evaluation of any significant breast
abnormality is mandatory because though women
commonly develop fibrocystic changes, breast cancer
is common also, and the signs and symptoms of fibrocystic changes overlap with those of breast cancer.
Certain benign changes in the breast may now be
linked to increased risk for breast cancer.

Diagnosis
The diagnosis of breast cancer is accomplished
by the biopsy of any suspicious lump or mammographic abnormality that has been identified.
(A biopsy is the removal of tissue for examination
by a pathologist. A mammogram is a low-dose,
2-view, x-ray examination of the breast.) The patient
may be prompted to visit her doctor upon finding a
lump in a breast, or she may have noticed skin dimpling, nipple retraction, or discharge from the nipple.
A patient may not have noticed a symptom or
abnormality, and a lump was detected by a screening
mammogram.
When a patient has no signs or symptoms
Screening involves the evaluation of women who
have no symptoms or signs of a breast problem.
Mammography has been helpful in detecting breast
cancer that cannot be identified on physical examination. However, 10%–13% of breast cancer does not
show up on mammography, and a similar number of
patients with breast cancer have an abnormal mammogram and a normal physical examination. These
figures emphasize the need for examination as part of
the screening process.
Screening
It is recommended that women get into the habit of
doing monthly breast self examinations to detect any
lump at an early stage. If an uncertainty or a lump is
found, evaluation by an experienced physician and a
645

Breast cancer

In 2002, 200,000 new cases of breast cancer were
diagnosed. About 45,000 women die of breast cancer
each year, accounting for 16% of deaths caused by
cancer in women. However, deaths from breast cancer
are declining in recent years, a reflection of earlier
diagnosis from screening mammograms and improving therapies.

Breast cancer

mammogram is recommended. The American Cancer
Society (ACS) has made recommendations for the use
of mammography on a screening basis. In 2003, the
ACS updated its guidelines concerning screening mammograms. The most notable change was that women
should begin annual screening at age 40 instead of age
50. (in the past, the ACS, recommended beginning
mammograms at age 40, but only ever one or two
years instead of annually.) Women at higher risk for
breast cancer should benefit from beginning screenings
at earlier ages and at more frequent intervals.
Because of the greater awareness of breast cancer
in recent years, screening evaluations by examinations
and mammography are performed much more frequently than in the past. The result is that the number
of breast cancers diagnosed increased, but the disease is
being diagnosed at an earlier stage than previously. The
earlier the stage of disease at the time it is discovered,
the better the long-term outcome (prognosis) becomes.
When a patient has physical signs or symptoms
A common finding that leads to diagnosis is the
presence of a lump within the breast. Skin dimpling,
nipple retraction, or discharge from the nipple are less
frequent initial findings prompting biopsy. Though
bloody nipple discharge is distressing, it is most often
caused by benign disease. Skin dimpling or nipple
retraction in the presence of an underlying breast
mass on examination is a more advanced finding.
Actual skin involvement, with edema or ulceration of
the skin, are late findings.
The presence of a breast lump is a common sign of
breast cancer. If the lump is suspicious and the patient
has not had a mammogram by this point, a study
should be done on both breasts prior to anything else
so that the original characteristics of the lesion can be
studied. The opposite breast should also be evaluated
mammographically to determine if other problems
exist that were undetected by physical examination.
Whether an abnormal screening mammogram or
one of the signs mentioned above followed by a mammogram prompted suspicion, the diagnosis is established by obtaining tissue by biopsy of the area. There
are different types of biopsy, each utilized with its own
indication. If signs of widespread metastasis are
already present, biopsy of the metastasis itself may
establish diagnosis.
Biopsy
Depending on the situation, different types of biopsy
may be performed. The types include incisional and
excisional biopsies. In an incisional biopsy, the physician
646

takes a sample of tissue, and in excisional biopsy,
the mass is removed. Fine needle aspiration biopsy and
core needle biopsy are kinds of incisional biopsies.
FINE NEEDLE ASPIRATION BIOPSY. In a fine needle
aspiration biopsy, a fine-gauge needle may be passed
into the lesion and cells from the area suctioned into
the needle can be quickly prepared for microscopic
evaluation (cytology). (The patient experiencing nipple discharge also can have a sample taken of the
discharge for cytological evaluation.) Fine needle
aspiration is a simple procedure that can be done
under local anesthesia, and will tell if the lesion is a
fluid-filled cyst or whether it is solid. The sample
obtained will yield much diagnostic information.
Fine needle aspiration biopsy is an excellent technique
when the lump is palpable and the physician can easily
hit the target with the needle. If the lesion is a simple
cyst, the fluid will be evacuated and the mass will
disappear. If it is solid, the diagnosis may be obtained.
Care must be taken, however, because if the mass is
solid and the specimen is non-malignant, a complete
removal of the lesion may be appropriate to be sure.
CORE NEEDLE BIOPSY. Core needle biopsies also are
obtained simply under local anesthesia. The larger piece
of tissue obtained with its preserved architecture may
be helpful in confirming the diagnosis short of open
surgical removal. An open surgical incisional biopsy is
rarely needed for diagnosis because of the needle techniques. If there remains question as to diagnosis, a
complete open surgical biopsy may be required.
EXCISIONAL BIOPSY. When performed, the excisional (complete removal) biopsy is a minimal outpatient procedure often done under local anesthesia.
NON-PALPABLE LESIONS. As screening increases,
non-palpable lesions demonstrated only by mammography are becoming more common. The use of x rays
and computers to guide the needle for biopsy or to
place markers for the surgeon performing the excisional biopsy are commonly employed. Some benign
lesions can be fully removed by multiple directed core
biopsies. These techniques are very appealing because
they are minimally invasive; however, the physician
needs to be careful to obtain a good sample.

Other tests
If a lesion is not palpable and has simple cystic characteristics on mammography, ultrasound may be utilized both to determine that it is a cyst and to guide its
evacuation. Ultrasound may also be used in some cases to
guide fine needle or core biopsies of the breast.
Computed tomography (CT) scans have only rare
in the evaluation of breast lesions. Magnetic resonance
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Staging
Once diagnosis is established and before treatment
is rendered, more tests are done to determine if the
cancer has spread beyond the breast. These tests include
a chest x ray and blood count with liver function tests.
Along with the liver function measured by the blood
sample, the level of alkaline phosphatase, an enzyme
from bone, is also determined. A radionuclear bone
scan may be ordered. This test looks at the places in
the body to which breast cancer usually metastasizes. A
CT scan also may be ordered. The physician will do a
careful examination of the axillae to assess likelihood of
regional metastasis. Sometimes, the physician removed
all of the axillary lymph nodes to assess breast cancer
stage. However, recent studies show great success with
sentinel lymph node biopsy. This technique removes the
sentinel lymph node, or that lymph node that receives
fluid drainage first from the area where the cancer is
located. If this node is free of cancer, staging can be
assigned accordingly. This method saves women the
discomfort and side effects associated with removing
additional lymph nodes in her armpit.
Using the results of these studies, clinical stage is
defined for the patient. This helps define treatment
protocol and prognosis. After surgical treatment, the
final, or pathologic, stage is defined as the true axillary
lymph node status is known. Detailed staging criteria
are available from the American Joint Commission
on Cancer Manual and are generalized here:


Stage 1—The cancer is no larger than 2 cm (0.8 in)
and no cancer cells are found in the lymph nodes.



Stage 2—The cancer is between 2 cm and 5 cm, and
the cancer has spread to the lymph nodes.



Stage 3A—Tumor is larger than 5 cm (2 in) or is
smaller than 5 cm, but has spread to the lymph
nodes, which have grown into each other.



Stage 3B—Cancer has spread to tissues near the
breast, (local invasion), or to lymph nodes inside
the chest wall, along the breastbone.



Stage 4—Cancer has spread to skin and lymph nodes
beyond the axilla or to other organs of the body.
Treatment

Surgery, radiation, and chemotherapy are all utilized in the treatment of breast cancer. Depending on
GALE ENCYCLOPEDIA OF MEDICINE

the stage, they will be used in different combinations
or sequences to effect an appropriate strategy for the
type and stage of the disease being treated.
SURGERY. Historically, surgical removal of the
entire breast and axillary contents along with the muscles down to the chest wall was performed as the lone
therapy, (radical mastectomy). In the last 25 years, as it
has been appreciated that breast cancer often spreads
early, surgery remains a primary option but other
therapies have risen in importance. Recent studies
have suggested that breast conserving treatment
improves the quality of life.

Today, surgical treatment is best thought of as a
combination of removal of the primary tumor and
staging of the axillary lymph nodes. A modified radical mastectomy involves removing the whole breast
along with the entire axillary contents but not the
muscles of the chest wall.
If the tumor is less than 1.5 (4 cm) in size and
located so that it can be removed without destroying
the reasonable cosmetic appearance of the residual
breast, just the primary tumor and a rim of normal
tissue will be removed. The axillary nodes will still be
removed for staging purposes, usually through a separate incision. Because of the risk of recurrence in the
remaining breast tissue, radiation therapy is used to
lessen the chance of local recurrence. This type of
primary therapy is known as lumpectomy, (or segmental mastectomy), and axillary dissection.
Sentinel lymph node biopsy, a technique for identifying which nodes in the axilla drain the tumor, has
been developed to provide selective sampling and
further lessen the degree of surgical trauma the patient
experiences.
When patients are selected appropriately based on
the preoperative clinical stage, all of these surgical
approaches have been shown to produce similar
results. In planning primary surgical therapy, it is
imperative that the operation is tailored to fit the
clinical circumstance of the patient.
The pathologic stage is determined after surgical
treatment absolutely defines the local parameters. In
addition to stage, there are other tests that are very
necessary to aid in decisions regarding treatment such
as adjuvant therapies. Adjuvant therapies are treatments utilized after the primary treatment to help
ensure that no microscopic disease exists and to help
prolong patients’ survival time.
RADIATION THERAPY. Like surgical therapy, radiation therapy is a local modality—it treats the tissue
exposed to radiation and not the rest of the body.

647

Breast cancer

imaging (MRI) has been used more often in recent
years to follow up on suspicious findings from mammograms or for certain patients.

Breast cancer

Radiation is usually given post-operatively after surgical
wounds have healed. The pathologic stage of the primary
tumor is now known and this aids in treatment planning.
The extent of the local surgery also influences the planning. Radiation may not be needed at all after modified
radical mastectomy for stage I disease, but is almost
always utilized when breast-preserving surgery is performed. If the tumor was extensive or if multiple nodes
were involved, the field of tissue exposed will vary
accordingly. Radiation is utilized as an adjunct to surgical therapy and is considered important to gaining local
control of the tumor. The use of radiation therapy does
not affect decisions for adjuvant treatment. In the past,
radiation was used as an alternative to surgery on occasion. However, now that breast-preserving surgical protocols have been developed, primary radiation treatment
of the tumor is no longer performed. Radiation also has
an important role in the treatment of the patient with
disseminated disease, particularly if it involves the skeleton. Radiation therapy can affect pain control and prevention of fracture in this circumstance.
DRUG THERAPY. Many breast cancers, particularly
those originating in post-menopausal women, are
responsive to hormones. These cancers have receptors
on their cells for estrogen and progesterone. Part of
primary tumor assessment after removal of the tumor
is the evaluation for the presence of these estrogen and
progesterone receptors. If they are present on the cancer cells, altering the hormone status of the patient will
inhibit tumor growth and have a positive impact on
survival. The drug tamoxifen binds up these receptors
on the cancer cells so that the hormones can’t have an
effect and, in so doing, inhibits tumor growth. If the
patient has these receptors present, tamoxifen is commonly prescribed for five years as an adjunct to primary
treatment. Adjuvant hormonal therapy with tamoxifen
has few side effects but they have to be kept in mind,
particularly the need for yearly evaluation of the uterus.
Other agents directed at altering hormone environment
are under study. Because of these agents, there is rarely
any need for surgical removal of hormone-producing
glands, such as the ovary or adrenal, that was sometimes necessary in the past.

In late 2003, cancer experts were beginning to
recommend a new group of drugs called aromatase
inhibitors (Arimidex, common name anastrozole, or
more recently Femara and Novartis, common name
letrozole). New guidelines also recommend letrozole
following five years of tamoxifen therapy. These drugs
fight breast cancer differently, but early research shows
they fight it as effectively and with fewer side effects.
Shortly after the modified radical mastectomy
replaced the radical mastectomy as primary surgical
648

treatment, survival after local treatment in stage II
breast cancer was improved by the addition of chemotherapy. Adjuvant chemotherapy for an interval
of four to six months is now standard treatment
for patients with stage II disease. The addition of
systemic therapy to local treatment in patients who
have no evidence of disease is performed on the basis
that some patients have metastases that are not currently demonstrable because they are microscopic. By
treating the whole patient early, before widespread
disease is diagnosed, the adjuvant treatment improves
survival rates from roughly 60% for stage II to about
75% at five years after treatment. The standard regimen of cytoxan, methotrexate, and 5-flourouracil,
(CMF), is given for six months and is well tolerated.
The regimen of cytoxan, adriamycin (doxorubicin),
and 5-floururacil, (CAF), is a bit more toxic but only
requires four months. (Adriamycin and cytoxin may
also be used alone, without the fluorouracil.) The two
methods are about equivalent in results. Adjuvant
hormonal therapy may be added to the adjuvant chemotherapy as they work through different routes.
The encouraging results from adjuvant therapy in
stage II disease have led to the study of similar therapy
in stage I disease. The results are not as dramatic, but
they are real. Currently, stage I disease is divided into
categories a, b, and c on the basis of tumor size. Stage
Ia is less than a centimeter in diameter. Adjuvant
hormonal or chemotherapy is now commonly recommended for stage Ib and Ic patients. The toxicity of the
treatment must be weighed individually for the patient
as patients with stage I disease have a survivorship of
over 80% without adjuvant chemotherapy.
If patients are diagnosed with stage IV disease or,
in spite of treatment, progress to a state of widespread
disease, systemic chemotherapy is utilized in a more
aggressive fashion. In addition to the adriamycin-containing regimens, the taxols (docetaxel and paclitaxel)
have been found to be effective in inducing remission.
On the basis of prognostic factors such as total
number of involved nodes over 10, aneuploid DNA
with a high synthesis value, or aggressive findings on
microscopic evaluation, some patients with stage II or
III disease can be predicted to do poorly. If their
performance status allows, they can be considered for
treatment with highly aggressive chemotherapy. The
toxicity is such that bone marrow failure will result. To
get around this anticipated side effect of the aggressive
therapy, either the patients will be transplanted with
their own stem cells, (the cells that will give rise to new
marrow), or a traditional bone marrow transplantation
will be required. This therapy can be a high-risk procedure for patients. It is given with known risk to patients
GALE ENCYCLOPEDIA OF MEDICINE

another drug, raloxifene, is as effective as tamoxifen in
reducing breast cancer risk in high-risk patients. That
study was begun in 1999, and participants were to be
monitored for five years.

For patients who are diagnosed with advanced
local disease, surgery may be preceded with chemotherapy and radiation therapy. The disease locally regresses
allowing traditional surgical treatment to those who
could not receive it otherwise. Chemotherapy and
sometimes radiation therapy will continue after the
surgery. The regimens of this type are referred to as
neo-adjuvant therapy. This has been proven to be effective in stage III disease. Neo-adjuvant therapy is now
being studied in patients with large tumors that are
stage II in an effort to be able to offer breast preservation to these patients.

And, while most breast cancer can’t be prevented,
it can be diagnosed from a mammogram at an early
stage when it is most treatable. The results of awareness
and routine screening have allowed earlier diagnosis,
which results in a better prognosis for those discovered.

A drug known as Herceptin (trastuzumab), a
monoclonal antibody, is now being used in the treatment of those with systemic disease. The product
of the Human Epidermal Growth Factor 2 gene,
(HER-2) is overexpressed in 25%–30% of breast cancers. Herceptin binds to the HER-2 receptors on the
cancer, resulting in the arrest of growth of these cells.

Prognosis
The prognosis for breast cancer depends on the
type and stage of cancer. Over 80% of stage I patients
are cured by current therapies. Stage II patients survive overall about 70% of the time, those with more
extensive lymph nodal involvement doing worse than
those with disease confined to the breast. About 40%
of stage III patients survive five years, and about 20%
of stage IV patients do so. In 2003, research showed
that young women who choose breast-conserving surgery are at higher risk for local recurrence and should
receive indefinite follow-up care from their physicians.

Prevention
The use of tamoxifen and other agents which alter
the hormone status of the patient are under study. The
National Surgical Adjuvant Breast and Bowel Project
(NSABP) with support from the National Cancer
Institute began a study in 1992 (called the Breast
Cancer Prevention Trial, or BCPT) studying the use
of tamoxifen as a breast cancer preventative for highrisk women. The results yielded from the study showed
that tamoxifen significantly reduced breast cancer
risk, and the U.S. Food and Drug Administration
approved the use of tamoxifen to reduce breast cancer
risk for high-risk patients in 1998. Another NSABP
study, known as STAR, is seeking to understand if
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Abelhoff, Armitage, Lichter, and Niederhuber. Clinical
Oncology Library. Philadelphia: Churchill Livingstone
1999.
Schwartz, Spencer, Galloway, Shires, Daly, and Fischer.
Principles of Surgery. New York: McGraw Hill, 1999.
PERIODICALS

‘‘Early Detection Saves Lives.’’ Women’s Health Weekly
(November 14, 2003): 13.
Esteva and Hortobagyi. ‘‘Adjuvant Systemic Therapy for
Primary Breast Cancer.’’ Surgical Clinics of North
America 79, no. 5 (October 1999): 1075-1090.
‘‘HRT Linked to Higher Breast Cancer Risk, Later
Diagnosis, Abnormal Mammograms.’’ Women’s
Health Weekly (July 17, 2003): 2.
Margolese, R. G., M. D. ‘‘Surgical Considerations For
Invasive Breast Cancer.’’ Surgical Clinics of North
America 79, no. 5 (October 1999): 1031-1046.
Munster and Hudis. ‘‘Adjuvant Therapy for Resectable
Breast Cancer.’’ Hematology Oncology Clinics of North
America 13, no. 2 (April 1999): 391-413.
‘‘New Human Breast and Ovarian Cancer Gene Described.’’
Biotech Week (December 31, 2003): 89.
Pennachio, Dorothy L. ‘‘Letrozole Improves Breast Cancer
Outlook.’’ Patient Care (December 2003): 4.
‘‘Quality of Life Seems to be Better After Conservative
Treatment of Breast Cancer.’’ Women’s Health Weekly
(July 17, 2003): 22.
‘‘Revised Guidelines Show Changes for Breast Cancer
Treatment.’’ Biotech Week (December 24, 2003): 296.
‘‘Sentinel Lymph Node Biopsy is Accurate for Staging.’’
Women’s Health Weekly (June 5, 2003): 4.
Shuster, et al. ‘‘Multidisciplinary Care For Patients With
Breast Cancer.’’ Surgical Clinics of North America 80,
no. 2 (April 2000): 505-533.
Smith, Robert A., et al. ‘‘American Cancer Society
Guidelines for Breast Cancer Screening: Update 2003.’’
Cancer (May-June 2003): 141.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800)ACS-2345. <http://
www.cancer.org>.
Cancer Care, Inc. 275 Seventh Ave., New York, NY
10001.(800) 813-HOPE. <http://
www.cancercare.org>.
649

Breast cancer

predicted to do poorly and only if it is felt they can
tolerate it. Most patients who receive this therapy
receive it as part of a clinical trial. At present, it is
unclear that such aggressive therapy can be justified.

Breast implants

Cancer Information Service of the NCI. 9000 Rockville Pike,
Building 31, Suite 10A18, Bethesda, MD 20892. 1-8004-CANCER. <http://wwwicic.nci.nih.gov>.
National Alliance of Breast Cancer Organizations. 9 East
37th St., 10th floor, New York, NY 10016. (888) 80NABCO.
National Coalition for Cancer Survivorship. 1010 Wayne
Ave., 5th Floor, Silver Spring, MD 20910. (301) 6508868.
National Women’s Health Resource Center. 120 Albany St.,
Suite 820, New Brunswick, NJ 08901. (877) 986-9472.
<http://www.healthywomen.org>.
OTHER

Breast Cancer Online. <http://www.bco.org/>.
National Alliance of Breast Cancer Organizations. <http://
www.nabco.org/>.
National Cancer Institute. <http://rex.nci.nih.gov/
PATIENTS/INFO_PEOPL_DOC.html>.

Richard A. McCartney, M.D.
Teresa G. Odle

Breast enlargement see Breast implants

I Breast implants
Definition
Breast implantation is a surgical procedure for
enlarging the breast. Breast-shaped sacks made of a
silicone outer shell and filled with silicone gel or saline
(salt water), called implants, are used.

Purpose
Breast implantation is usually performed to
make normal breasts larger for cosmetic purposes.
Sometimes a woman having a breast reconstruction
after a mastectomy will need the opposite breast
enlarged to make the breasts more symmetric.
Breasts that are very unequal in size due to trauma
or congenital deformity may also be corrected with an
enlargement procedure.

Precautions
A woman in poor health or with a severe chronic
disease is not a good candidate for this procedure.

Description
A cosmetic breast enlargement is usually an outpatient procedure. It may be done under local or
650

A silicone breast implant. (Photograph by Dale O’Dell, The
Stock Market. Reproduced by permission.)

general anesthesia, depending on patient and physician
preference. The incision is made through the armpit,
under the breast, or around the areola (the darkened
area around the nipple). These techniques create the
most inconspicuous scars. The implant is placed
between the breast tissue and underlying chest muscle,
or under the chest muscle. The operation takes approximately one to two hours. The cost of a cosmetic procedure is rarely covered by insurance. However, if
enlargement is part of breast reconstruction after a
mastectomy, health plans may pay for some or all of
it. The surgeon’s fee ranges from $2,700-$4,200 and up.
The procedure may also be called breast augmentation
or augmentation mammaplasty.

Preparation
Before the surgery is performed, the woman
should have a clear understanding of what her new
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Breast infection see Mastitis

Breast reconstruction

breasts will look like. She and her physician should
agree about the desired final result. Many surgeons
find it helpful to have the patient review before and
after pictures, to clarify expectations.

Breast radiography see Mammography

Aftercare
Driving and normal activities may be restricted for
up to one week. Stitches are usually removed in seven to
10 days. Typically, a woman can resume all routines,
including vigorous exercise, in about three weeks. The
scars will be red for approximately one month, but will
fade to their final appearance within one or two years.

Risks
Risks which are common to any surgical procedure include bleeding, infection, anesthesia reaction,
or unexpected scarring. A breast enlargement may
also result in decreased sensation in the breast, or
interference with breast-feeding. Implants can also
make it more difficult to read and interpret mammograms, possibly delaying breast cancer detection. Also,
the implant itself can rupture and leak, or become
displaced. A thick scar that normally forms around
the implant, called a capsule, can become very hard.
This is called capsular contracture, and may result in
pain and/or an altered appearance of the breast. The
older the implant, the greater the chances that these
problems will occur.
There has been intermittent publicity about possible health risks from breast implants. Most concerns
have focused on silicone gel-filled implants. As of
1992, the Food and Drug Administration (FDA)
restricted the use of this type of implant, and ordered
further studies. Today only saline-filled implants are
used for cosmetic breast surgery. Recent studies have
shown no evidence long-term health risks from silicone implants. However, research on the possible links
between these implants and autoimmune or connective tissue diseases is continuing.

I Breast reconstruction
Definition
Breast reconstruction is a series of surgical procedures performed to recreate a breast. Reconstructions
are commonly done after one or both breasts are
removed as a treatment for breast cancer. Also, a
breast may need to be refashioned for other reasons,
such as trauma or abnormalities that occur during
breast development.

Purpose
Many authorities consider reconstruction an
integral part of the therapy for breast cancer. A
breast that appears natural offers a sense of wholeness and normalcy, which can aid in the psychological recovery from breast cancer. It eliminates the need
for an external prosthesis (false breast), which many
women find physically uncomfortable as well as
inconvenient.

Precautions
Not all women are good candidates for breast
reconstruction. Overall poor physical health, or specific problems such as cigarette smoking, obesity, high
blood pressure, or diabetes, will increase the chance of
complications. Also, a difficult and/or prolonged
recovery period or failure of the reconstruction may
be a result. A woman’s physical ability to cope with
major surgery and recuperation also need to be
considered.

Description
Normal results
Breasts of expected size and appearance would be
the normal results of this surgery.
Resources
ORGANIZATIONS

American Society of Plastic and Reconstructive Surgeons.
44 E. Algonquin Rd., Arlington Heights, IL 60005.
(847) 228-9900. <http://www.plasticsurgery.org>.

Ellen S. Weber, MSN
GALE ENCYCLOPEDIA OF MEDICINE

Breast reconstruction is done in two stages, with
the ultimate goal of creating a breast which looks and
feels as natural as possible. It is important to remember that while a good result may mimic a normal
breast closely, there will inevitably be scars and loss
of sensation. The reconstructed breast cannot be
exactly like the original.
The first step is to form a structure called a breast
mound. This can be accomplished using artificial
materials called breast implants, or by using tissues
from other parts of the woman’s body. The second
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Breast reconstruction

Breast implant

Latissimus dorsi procedure

TRAM flap procedure
Breast reconstruction surgery may be performed by inserting an artificial substance, or implant, to replace breast tissue.
Autologous reconstruction, in which a woman’s own tissues are used, includes the latissimus dorsi flap, where skin and muscle
taken from the back is rotated around to the breast area, and the TRAM flap, in which abdominal fat and muscle are tunneled
under the skin to the breast area. (Illustration by Electronic Illustrators Group.)

step involves creating a balance between the newly
constructed breast and the breast on the opposite
side. The nipple and areolar complex (darker area
around the nipple) are recreated. This is usually done
several months after the mound is created, to allow
swelling to go down. Other procedures may be necessary, such as lifting the opposite breast (mastopexy),

652

or making it larger or smaller to match the reconstructed breast.
Timing, immediate or delayed reconstruction
While immediate reconstruction (IR) is not recommended for women with breast cancer who need to
undergo other, more important treatments, breast
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Autologous—From the same person. An autologous breast reconstruction uses the woman’s own
tissues. An autologous blood transfusion is blood
removed then transfused back to the same person at
a later time.
Capsular contracture—Thick scar tissue around a
breast implant, which may tighten and cause discomfort and/or firmness.
Flap—A section of tissue moved from one area of
the body to another.
Free flap—A section of tissue detached from its
blood supply, moved to another part of the body,
and reattached by microsurgery to a new blood
supply.
Mastopexy—Surgical procedure to lift up a breast.
May be used on opposite breast to achieve symmetrical appearance with a reconstructed breast.
Pedicle flap—Also called an attached flap. A section of tissue, with its blood supply intact, which is
maneuvered to another part of the body.

reconstruction can be done almost anytime. It even can
be done during the same procedure as the mastectomy,
or it can be delayed. There are psychological benefits to
IR. The ability to return to normal activities and routines is often enhanced when reconstruction follows
immediately after mastectomy. A better appearance
may result from IR. There is less skin removal, often
resulting in a shorter scar. The surgeon is better able to
preserve the normal boundaries of the breast, so it is
easier to match the opposite breast more closely.
The cost of IR is generally lower than the cost of
delayed reconstruction (DR). There is one fewer operation and hospital stay. Surgeon’s fees may be lower for
a combined procedure than for two separate surgeries.
There are disadvantages of IR as well. The surgery
itself is longer, causing more time under anesthesia.
Post-operative pain and recovery time will be greater
than for mastectomy alone.
Other authorities contend that delayed reconstruction (DR) offers different physical and psychological advantages. The initial mastectomy procedure
alone takes less time, and has a shorter recovery period
and less pain than mastectomy and IR. The patient
has more time to adjust to her diagnosis and recover
from additional therapy. She is better able to research
her options, and to formulate realistic goals for
GALE ENCYCLOPEDIA OF MEDICINE

The psychological stress of living without a breast
is a disadvantage of DR. The extra procedure DR
entails results in higher costs. Although initial recovery is faster, an additional recuperation period is
required after the delayed operation.
Type of reconstruction
There are two basic choices for breast reconstruction. The breast tissue can be replaced with an implant
or the breast is created using some of the woman’s own
tissues (autologous reconstruction).
ARTIFICIAL IMPLANTS. In general, implant procedures take less time, and are less expensive than autologous ones. Implants are breast shaped pouches.
They are made of silicone outer shells, which may be
smooth or textured. The inside may contain silicone
gel, saline (salt water), or a combination of both.

An implant may be a fixed volume type, which
cannot change its size. Implants that have the capacity
to be filled after insertion are called tissue expanders.
These may be temporary or permanent.
The initial procedure for any implant insertion
uses the mastectomy incision to make a pocket of
tissue, usually underneath the chest wall muscle. In
DR, the mastectomy scar may be re opened and used
for this purpose, or a more cosmetic incision may be
made. The implant is inserted into the pocket, the skin
is stretched as needed and stitched closed.
If there is inadequate tissue to achieve the desired
size, or a naturally sagging breast is desired, a tissue
expander is used. It resembles a partially deflated
balloon, with an attached valve or port through
which saline can be injected. After the initial surgical
incision is healed, the woman returns to the doctor’s
office, on a weekly or bi-weekly basis, to have small
amounts of saline injected. Injections can continue for
about six to eight weeks, until the preferred size is
obtained. In some cases it may be overfilled, and
later partially deflated to allow for a more pliable,
natural result. A temporary tissue expander will be
removed after several months and replaced with a
permanent implant.
IR surgery using an implant takes approximately
two to three hours, and usually requires up to a three
day hospital stay. Implant insertion surgery, as part of
DR, takes one to two hours and can sometimes be
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Breast reconstruction

KEY TERMS

reconstruction. Some reconstructive surgery requires
blood transfusions. With DR, the patient can donate
her own blood ahead of time (autologous transfusion),
and/or arrange to have family and friends donate
blood for her use (directed donation).

Breast reconstruction

done as an outpatient, or it or it may entail overnight
hospitalization.
AUTOLOGUS RECONSTRUCTION. Attached flap
and free flap are two types of surgery where a woman’s
tissue is used in reconstruction. An attached flap uses
skin, muscle, and fat, leaving blood vessels attached to
their original source of blood. The flap is maneuvered
to the reconstruction site, keeping its original blood
supply for nourishment. This may also be known as a
pedicle flap. The second kind of surgery is called a free
flap. This also uses skin, muscle, and fat, but severs the
blood vessels, and attaches them to other vessels where
the new breast is to be created. The surgeon uses a
microscope to accomplish this delicate task of sewing
blood vessels together. Sometimes the term microsurgery is used to refer to free flap procedures. Either type
of surgery may also be called a myocutaneous flap,
referring to the skin and muscle used.

The skin and muscle used in autologous reconstruction can come from one of several possible places
on the body, including the abdomen (TRAM flap or
‘‘tummy tuck’’), the back (latissimus dorsi flap), or the
buttocks (gluteus maximus free flap).

related problems. Careful reading of insurance policies, including checking on the need for pre-approval
and/or a second opinion, is strongly recommended.

Preparation
Routine preoperative preparations, such as taking
nothing to eat or drink the night before surgery are
needed for reconstructive procedures. Blood transfusions are often necessary for autologous reconstructive surgeries. The patient may donate her own blood,
and/or have family and friends donate several weeks
before the surgery.
Emotional preparation is also important. Breast
reconstruction will not resolve a psychological problem
the woman had before mastectomy, nor make an
unstable relationship strong. An expectation of physical perfection is unrealistic. A woman who cites any of
these reasons for reconstruction shows that she has not
been adequately informed or prepared. Complete
understanding of the benefits and limitations of this
surgery is necessary for a satisfactory result.

Aftercare
Finishing the reconstruction
Other procedures may be necessary to achieve the
goal of symmetrical breasts. It may be necessary to
make the opposite breast larger (augmentation), smaller (reduction), or higher (mastopexy). These, or any
other refinements should be completed before the
creation of a nipple and areola. Tissue to form the
new nipple may come from the reconstructed breast
itself, the opposite breast, or a more distant donor site,
such as the inner thigh or behind the ear. The nipple
and areolar construction is usually an outpatient procedure. A final step, often done in the doctor’s office, is
tattooing the new nipple and areola, to match the
color of the opposite nipple and areola as closely as
possible.
Insurance
Insurance coverage for breast reconstruction varies widely. Some policies will allow procedures on the
affected breast, but refuse to pay for alterations to the
opposite breast. Other plans may cover the cost of an
external prosthesis, or reconstructive surgery, but not
both. As of January 1998, 25 states had different laws
regarding required insurance coverage for post mastectomy reconstruction.
Implants may pose additional insurance concerns.
Some companies will withdraw coverage for women
with implants, or add a disclaimer for future implant654

The length of the hospital stay, recovery period,
and frequency of visits to the doctor after surgery varies
considerably with the different kinds of reconstruction.
In general, autologous procedures require longer hospitalization and recovery time than implant procedures.
Bandages and drainage tubes remain in place for at
least a day for all surgeries. Microsurgical or free flaps
are most closely monitored in the first day or two after
surgery. The circulation to the breast may be checked as
often as every hour. Complete breast reconstruction
requires at least one additional surgery to create a
nipple and areola. Scars may remain red and raised
for a month or longer. The true, final appearance of
the breasts will not be visible for at least one year.

Risks
Some women have reported various types of autoimmune related connective-tissue disorders, which
they attribute to their implants–usually involving silicone gel implants. Lawsuits have been filed against the
manufacturers of implants. Food and Drug
Administration guidelines, issued in 1992, now limit
their use to women who need to replace an existing
silicone gel-filled implant, have had surgery for breast
cancer, or have a medical condition which results in
serious breast abnormality. In addition, patients must
sign a consent form which details the potential risks of
silicone gel-filled implants, and become enrolled in a
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The FDA issued a status report on Breast Implant
Safety in 1995, and revised it in March 1997. It noted
that studies so far have not shown a serious increase
in the risk of recognized autoimmune diseases in
women with silicone gel-filled breast implants. It also
addressed concerns about other complications and
emphasized the need for further study of this issue.
There are a number of risks common to any surgical procedure such as bleeding, infection, anesthesia
reaction, or unexpected scarring. Hematoma (accumulation of blood at the surgical site), or seroma (collection of fluid at the surgical site) can delay healing if not
drained. Any breast reconstruction also poses a risk of
asymmetry and/or the need for unplanned surgical revision. Persistent pain is another potential complication
possible with all types of breast reconstruction.
Implants have some unique problems that may
develop. A thick scar, also called a capsule, forms
around the implant, as part of the body’s normal
reaction to a foreign substance. Capsular contracture
occurs when the scar becomes firm or hardened. This
may cause pain and/or change the texture and appearance of the breast. Implants can rupture and leak,
deflate, or become displaced. The chances of capsular
contracture or rupture increase with the age of the
implant. These complications can usually be remedied
with outpatient surgery to loosen the capsule or
remove and/or replace the implant as needed. There
is some evidence that using implants with textured
surfaces may decrease the incidence of these problems.
An implant tends to remain firm indefinitely. It will
not grow larger or smaller as the woman’s weight
changes. Asymmetry can develop if a woman gains
or loses a large amount of weight.
The autologous procedures all carry a risk of flap
failure–loss of blood supply to the tissue forming the
new breast. If a large portion of the flap develops
inadequate blood supply, another reconstructive technique may be necessary. TRAM flap procedures can
result in decreased muscle tone and weakness in the
abdomen and/or abdominal hernia. Arm weakness
may occur after latissimus dorsi flap surgery.

Normal results
A normal result of breast reconstruction depends
on the woman’s goals and expectations. It will not be
the same as the breast it replaces. In general, it should
be similar in size and shape to the opposite breast, but
GALE ENCYCLOPEDIA OF MEDICINE

will have less sensation and be less mobile than a
natural breast. A reconstruction using implants will
usually be firmer and rounder than the other breast. It
may feel cooler to touch, depending on the amount of
tissue over it. Scars are unavoidable, but should be as
unobtrusive as possible.
Breast reconstruction surgery may be performed
by inserting an artificial substance, or implant, to
replace breast tissue. Autologous reconstruction, in
which a woman’s own tissues are used, includes the
latissimus dorsi flap, where skin and muscle taken
from the back is rotated around to the breast area,
and the TRAM flap, in which abdominal fat and
muscle are tunneled under the skin to the breast area.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
American Society of Plastic and Reconstructive Surgeons.
44 E. Algonquin Rd., Arlington Heights, IL 60005.
(847) 228-9900. <http://www.plasticsurgery.org>.

Ellen S. Weber, MSN

I Breast reduction
Definition
Breast reduction is a surgical procedure performed in order to decrease the size of the breasts.

Purpose
Women with very large breasts (macromastia or
mammary hyperplasia) seek breast reduction for relief
of pain in the back, shoulder, and neck. They may also
feel uncomfortable about their breast size and have
difficulty finding clothing that will fit properly.
Additionally, breast reduction may be needed after
reconstructive surgery following the surgical removal
of cancerous breast tissue (mastectomy), to make the
breasts more symmetric.
Men who have enlarged breasts (gynecomastia)
may also be candidates for breast reduction.
However, excessive alcohol intake, smokingmarijuana,
or using anabolic steroids may cause gynecomastia,
and surgery is not recommended for men who continue to use these products.
655

Breast reduction

long range study. Saline filled implants are permitted
for all uses, although manufacturers must collect data
on possible risks.

Breast self-examination

KEY TERMS
Gynecomastia—Overly developed or enlarged
breasts in a male.
Macromastia—Excessive size of the breasts.
Mammary hyperplasia—Increased size of the breast.

Precautions
Breast reduction is not recommended for women
whose breasts are not fully developed or who plan to
breast feed.

Description
Breast reduction may also be called reduction mammaplasty. It is most often done in the hospital, under
general anesthetic. However, studies have suggested that
an outpatient procedure, using local anesthetic and mild
sedation may be appropriate for some patients. The
operation takes approximately two to four hours. The
most commonly made incision encircles the areola (darkened area around the nipple) and extends downward
and around the underside of the breast. This produces
the least conspicuous scar. The excess tissue, fat, and
skin are removed, and the nipple and areola are repositioned. In certain cases, liposuction (fat suctioning) is
used to remove extra fat from the armpit area. A hospital stay of up to three days may be needed for recovery.
If deemed medically necessary, breast reduction is
covered by some insurance plans. However, a specified
amount of breast tissue may need to be removed in
order to qualify for coverage. Surgeon’s fees range
from $4,800-$6,500 and up.

Preparation
Consultation between surgeon and patient is
important to ensure that the woman understands and
agrees with the expected final results of the procedure.
Measurements and photographs may be taken. Many
doctors also recommend a mammogram before the
operation, to make sure there is no cancer.

Aftercare
After the surgery, an elastic bandage or special
supportive bra is placed over gauze bandages and drainage tubes. The bandages and tubes are removed in a
day or two. The bra will need to be worn around the
clock for several weeks. Stitches are removed one to
656

three weeks after the operation. Normal activities,
including sexual relations may be restricted for several
weeks. Scars will typically remain red, and perhaps
lumpy for up to several months, but will gradually fade
and become less noticeable. It may take up to a year
before the breasts achieve their final position and size.

Risks
Risks common to any operation include bleeding,
infection, anesthesia reactions, or unexpected scarring.
Breast reduction may result in decreased feeling in the
breasts or nipples and/or impaired ability to breastfeed.
When healing is complete, the breasts may be slightly
uneven, or the nipples may be asymmetric.

Normal results
Smaller breast size should be achieved, and with
that, the accompanying pain and discomfort should be
alleviated.
Resources
ORGANIZATIONS

American Society of Plastic and Reconstructive Surgeons.
44 E. Algonquin Rd., Arlington Heights, IL 60005.
(847) 228-9900. <http://www.plasticsurgery.org>.

Ellen S. Weber, MSN

I Breast self-examination
Definition
A breast self-examination (BSE) is an inspection
by a woman of her breasts to detect breast cancer.

Purpose
A BSE is one of three tests the American Cancer
Society recommends to help detect breast cancer in its
earliest stages. By regularly examining her own
breasts, a woman is more likely to find any changes
that may have occurred. The best time to perform a
BSE is about a week after a woman’s period ends,
when her breasts are not tender or swollen. If her
periods are not regular, a BSE should be completed
on the same day every month. A BSE should also be
regularly completed by women who are pregnant,
breastfeeding, or have breast implants. By combining
a BSE with a mammography and clinical breast
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doctor should examine the area immediately. Other
trouble signs that should not be ignored include:


change in breast size or shape



dimpling or puckering of the skin



redness, swelling, or warmth that does not go away



a pain in one area that does not vary with a woman’s
monthly cycle



a nipple that pulls in



discharge from the nipple that begins suddenly and
appears only in one breast



one nipple that has an itchy, sore, or scaling area

Description
To complete a monthly BSE:






When lying down, place a pillow under the right
shoulder and position the right arm behind the
head. Using the finger pads of the three middle fingers on the left hand, check the entire breast area.
Use small circles and follow an up-and-down pattern
while pressing firmly enough to know how the breast
feels from month to month. This exam should then
be repeated on the left breast using the finger pads of
the right hand with the pillow under the left shoulder.
When standing before a mirror, any changes in the
shape or look of the breasts should be checked. In
order to look for any skin or nipple changes such as
dimpling or nipple discharge, the arms should first be
placed at the sides and then overhead. Hands are
then placed firmly on hips to flex chest muscles, and
then the body should be bent forward.
When taking a shower, the right arm should be
raised. By using soapy hands and fingers flat the
right breast and outer part of the breast can be
examined. The same small circles and up-and-down
pattern used when lying down should be used in an
upright position. Repeat on the left breast.

Preparation
Before beginning a monthly BSE, a woman’s
breasts should be completely exposed.

Normal results
Each woman’s breasts has their own normal look
and feel. By completing a BSE each month, a woman
can determine what is normal for her and check for
changes that may arise. A regular pattern of lumpiness
in the breasts is normal.

Abnormal results
If any changes are noticed during a monthly BSE,
such as a new, hard lump in the breast or underarms, a
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Resources
BOOKS

Altman, Roberta, and Michael J. Sarg. ‘‘Breast Self-examination.’’ The Cancer Dictionary. Checkmark Books,
2000.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800)ACS-2345. <http://
www.cancer.org>.
Komen Foundation. 5005 LBJ Freeway, Suite 250, Dallas,
TX 75244. (972) 855-1600. <http://www.komen.org>.
OTHER

‘‘How to do a Breast Self-Exam.’’ Women.com. May 5,
2001. <http://www.women.com>.

Beth A. Kapes

Breast sonogram see Breast ultrasound

I Breast ultrasound
Definition
Breast ultrasound (or sonography) is an imaging
technique for diagnosing breast disease, such as cancer. It uses harmless, high frequency sound waves to
form an image (sonogram). The sound waves pass
through the breast and bounce back or echo from
various tissues to form a picture of the internal structures. It is not invasive and involves no radiation.

Purpose
Breast ultrasound may be used in several ways.
The most common application is to investigate a
specific area of the breast where a problem is suspected. A palpable lump and/or a lump or density
657

Breast ultrasound

examination, a woman is offered the best opportunity
for reducing chances of death from breast cancer
through early detection. Close to 90% of breast cancers are found through a BSE. The American Cancer
Society recommends that beginning at the age of 20,
women complete a BSE each month by feeling for
lumps or anything suspicious, as well as looking at
their breasts carefully in a mirror for any changes in
contour, swelling, dimpling, puckering of the skin, or
changes in the nipple.

Breast ultrasound

KEY TERMS
Cyst—A thin-walled, fluid-filled benign structure
in the breast.
Ductal carcinoma—A type of cancer that accounts
for as much as 80% of breast cancers. These tumors
feel bigger than they look on ultrasound or
mammogram.
Fibroadenoma—A benign breast growth made up
of fibrous tissue. It is the most common mass in
women under 35 years of age, and is found in
both breasts in 3% of cases.
A breast ultrasound image. (Custom Medical Stock Photo.
Reproduced by permission.)

discovered by x-ray imaging (mammogram) can be
further evaluated by ultrasound. It is especially helpful in distinguishing between a fluid-filled cyst and a
solid mass. It also can identify small lesions that are
too tiny to be felt.
Breast ultrasound is often the first study performed to evaluate masses in women under 35 whose
mammograms can be difficult to interpret due to
the density of their breast tissue. In 2003, a new
study found that ultrasound was more accurate than
mammography at diagnosing breast cancer in women
under age 45. However, mammography still works as
a screening tool, with breast ultrasound as the followup examination. Another study in that year found that
combining ultrasound with magnetic resonance imaging (MRI) direction greatly improved diagnostic
decisions about breast cancer lesions. The lesions
detected by MRI could also be localized using ultrasound needle guidance for follow-up biopsy.
The lack of radiation used with ultrasound makes
it ideal for studying breast abnormalities in women
who are pregnant. Assessing breast implants for leakage or rupture is another use for ultrasound. Breast
inflammation, where pockets of infection or abscesses
may form, can be diagnosed and monitored by
ultrasound.
Thickened and swollen breast skin may be a sign
of inflammatory breast cancer. Ultrasound can sometimes identify a cancerous growth within the breast
causing the thickened skin. These cases are usually
followed by a core biopsy guided by ultrasound.
Breast ultrasound is employed to observe and
guide a needle for several interventional procedures.
These include cyst aspiration, fine needle aspiration,
large core needle biopsy (as a first step in determining
658

Infiltrating lobular carcinoma—A type of cancer
that accounts for 8% to 10% of breast cancers. In
breasts that are especially dense, ultrasound can be
useful in identifying these masses.
Microcalcifications—Tiny flecks that are too small
to be felt. They are important markers of cancer that
show up on ultrasound and mammogram.
Mucinous (colloid) carcinoma—A type of cancer
that accounts for 1% to 2% of breast cancers.
Resembles medullary carcinoma in ultrasound and
mammogram, but usually affects older women.
Nonpalpable—Cannot be felt by hand. In cancer,
growths that are nonpalpable are too small to be felt,
but may be seen on ultrasound or mammogram.
Papillary carcinoma—A type of breast cancer that
primarily occurs in older women. On ultrasound,
this type of tumor may look like a solid or complex
mass, or it may show up as solid tissue protruding
into a cyst.
Tubular carcinoma—A type of cancer that accounts
for approximately 1% to 2% of breast cancers. Can
appear small on ultrasound or mammogram.

treatment for a lesion that is likely to be cancerous),
and needle localization in surgical breast biopsy.
Biopsies guided by ultrasound have distinct advantages. Patients usually find that the procedure is
less traumatic and more comfortable than surgical
biopsies. Ultrasound is known for its accuracy in
determining how far a cancerous growth extends
into the surrounding tissue in lesions that cannot be
felt. Biopsies guided by ultrasound are generally less
costly than surgical biopsies. Additionally, if the
abnormality that requires biopsy can be seen on both
a mammogram and ultrasound, an ultrasound-guided
biopsy is often more comfortable for the patient as no
compression is necessary.
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Ultrasound can be done in a doctor’s office or
another outpatient setting, such as a hospital or imaging center.
The patient removes her clothing from the waist
up and puts on a hospital gown, open in the front. She
lies on her back or side on an examining table. A gel
that enhances sound transmission is spread over the
area to be examined. The technologist then places a
transducer, an instrument about the size of an electric
shaver, against the skin. The images from reflected
sound waves appear on a monitor screen.
A physician called a radiologist interprets the
images obtained from ultrasound imaging. In 2003, it
was reported that new computer-aided diagnosis
(CAD) technology that had recently been widely
added to mammography may help improve ultrasound as well. The CAD system uses computer algorithms applied to a three-dimensional ultrasound
image to assign scores to mass characteristics.
Though the technology will not replace human observation and judgment, it may soon be added to support
the radiologist’s interpretation.
A good ultrasound study is difficult to obtain if
the patient is unable to remain quietly in one position.
Obesity may hinder clear viewing of internal structures, and the accuracy of an ultrasound study is
highly dependent on the skill of the person performing
the examination. The images recorded vary with the
angle and pressure of the transducer and the equipment settings. The examination may take from 30 to
45 minutes. Most insurance plans cover the cost of an
ultrasound examination.

Normal results
An ultrasound examination may reveal either normal tissue or a benign condition such as a cyst.
Ultrasound can confidently diagnose a benign structure that has certain characteristics of a simple cyst. In
the case of a simple cyst with no symptoms, additional
treatment beyond continued observation is usually not
needed.

Abnormal results
A potentially malignant mass can be identified by
breast ultrasound. Abnormal results fall into the following categories: benign fibrous nodule, complex
cyst, suspicious lesion, and lesion highly suggestive of
cancer. In cases where ultrasound shows the presence
of a complex cyst or fibrous nodule, a biopsy is
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justified because 10% to 15% of these growths are
malignant. Lesions falling into the last two categories
(suspicious or highly suggestive of cancer) have a
higher chance of being cancerous, and should be investigated further, either by biopsy or surgery.
Breast cancers such as the following may be identified on ultrasound: ductal carcinoma, infiltrating
lobular carcinoma, medullary carcinoma, mucinous
(colloid) carcinoma, tubular carcinoma, and papillary carcinoma. On ultrasound, the shape of a lesion
and the type of edges it has can sometimes indicate if
it is benign or cancerous, but there are exceptions.
For example, benign fibroadenomas are usually oval,
and some cancers can be similarly shaped. Cancerous
tumors usually have jagged edges, but some benign
growths can have these edges as well. Ultrasound is
not a definitive test. Tissue diagnosis is often
required.
Resources
PERIODICALS

‘‘CAD Software Improves Breast Ultrasound, Digital
Mammograms.’’ Cancer Weekly (December 23,
2003): 13.
Rubin, Eva, et al. ‘‘Reducing the Cost of Diagnosis of Breast
Carcinoma: Impact of Ultrasound and Imaging–
Guided Biopsies on a Clinical Breast Practice.’’ Cancer
91 (January 2001): 324-31.
Smith, LaNette F., et al. ‘‘Intraoperative Ultrasound–
guided Breast Biopsy.’’ The American Journal of
Surgery 180 (December 2000): 419-23.
Trevino, Merlino. ‘‘MR-directed US Provides Economical
Breast Diagnosis — Ultrasound Characterizes
Indeterminate Lesions Already Found by MRI.’’
Diagnostic Imaging (April 1, 2003): 59.
Velez, Nitzet, et al. ‘‘Diagnostic and Interventional
Ultrasound for Breast Disease.’’ The American Journal
of Surgery 180 (October 2000): 284-7.

Ellen S. Weber, MSN
Teresa G. Odle

Breast x ray see Mammography

I Breech birth
Definition
Breech birth is the delivery of a fetus (unborn
baby) hind end first. Between 3-4% of fetuses will
start labor in the breech position, which is a potentially dangerous situation.
659

Breech birth

Description

Breech birth

Placenta

Uterus

Umbilical cord
Breech Birth

Approximately 3-4% of babies will start labor in the breech
(buttocks first) position. While this is a potentially dangerous situation, many full-term babies can be safely delivered
from the breech position. (Illustration by Electronic Illustrators
Group.)

Description
Throughout most of pregnancy, the developing
fetus is completely free to move around within the
uterus. Between 32-36 weeks, it becomes so large that
movement is restricted. It is much harder for the fetus
to turn over, so whatever position it has assumed by
this point is likely to be the same position that he or she
will be in when labor begins.
For reasons that are not fully understood, almost
all unborn babies settle into a head down position. The
fetus is upside down in the uterus, and the head will
lead the way during the birth process.
Unfortunately, some fetuses do not cooperate.
Most of these are in the breech position. The buttocks
lead the way out of the uterus, and the legs are folded
in front of the body (frank breech). Delivery from the
breech position poses far more risks than delivery head
first (vertex position).
The biggest part of the fetus’s body is usually its
head. If the head fits through the mother’s pelvis, then
the rest of the fetus’s body should slip out fairly easily.
If the fetus is born bottom first, it is possible that
the body will fit through the mother’s pelvis, but the
baby’s head will get stuck at the level of the chin. This
condition, known as a trapped head, is very dangerous.
660

When the baby’s head comes first, it has a chance
to ‘‘mold’’ during labor. The bones of the baby’s skull
are not yet fastened together the way they are in a child
or adult’s skull, meaning that the bones of the baby’s
skull can move. During the long hours of labor the
skull can change shape to fit through the pelvis more
easily, which is why many babies are born with a ‘‘cone
head’’. If the baby is born from the breech position,
the skull does not have a chance to change shape to fit
the pelvis, and it is even more likely to get stuck.
If the baby’s head gets trapped, the possibility of
injury is high. Once the baby’s body is born, the umbilical cord usually stops pulsating (just as it would
during a normal delivery). This cuts off the oxygen
supply from the mother to the baby. If the baby’s head
is still inside the uterus the baby cannot yet breathe on
its own. Therefore, it is essential to deliver the baby as
quickly as possible.
The life saving attempts to deliver the baby’s head
can cause injury to the baby’s neck or head resulting in
permanent handicaps. In extreme cases, if the baby
cannot be delivered within a few minutes, the baby
might die. Obviously, it is critical to avoid a breech
delivery with a trapped head.
Of course, many babies are safely delivered from
the breech position. There are certain factors that
make a breech delivery more likely to be successful: if
ultrasound (a technique that uses sound waves to
visualize the fetus) shows that the fetus is in the frank
breech position, the fetus’s head is tucked on its chest,
and the fetus is not big, it is less likely that its head will
get stuck.
Among breech babies born after the full ninemonth term, smaller babies usually do better. This is
not true for premature babies. Premature babies are
more likely to have a trapped head because the body of
a premature baby is usually much smaller than his or
her head. Premature babies are generally not delivered
from the breech position.
The risks of vaginal breech delivery can be
avoided by delivering the baby through a surgical
procedure (cesarean section, also known as c-section).
For the past twenty years, cesarean section has been
recommended when the fetus is breech. More recently,
many providers have offered the option of version,
attempting to turn the fetus within the uterus to a
head first position before labor begins.
Version is based on a very simple idea. If a fetus in
the breech position does a somersault, it will end up
head down. During a version, the obstetrician tries to
make the fetus do a somersault.
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During the procedure, the obstetrician places his
or her hands on the mother’s abdomen to feel the
location of the unborn baby’s buttocks and head.
The buttocks are lifted up slightly and the doctor
pushes on the baby’s head to encourage him to perform a somersault. It may take several tries before the
fetus cooperates, but over half will eventually turn.
A version is not appropriate for every fetus who is
in the breech position at the end of pregnancy. It can
only be tried if there is one fetus in the uterus, if the
placenta is not lying in front of the fetus, and if the
umbilical cord does not appear to be wrapped around
the fetus at any point.

Causes and symptoms
The cause of breech birth is not known. There are
generally no identifiable symptoms. However, some
women can tell the position of the fetus by where
they feel the fetus kicking. Most women cannot tell
what position the fetus is in at any given moment.

Diagnosis
A health care provider can often tell the position
of the fetus by feeling it through the wall of the
mother’s abdomen. Another clue to the position is
the location where the heartbeat is heard best. If the
fetus’s heartbeat is best heard below the level of the
mother’s navel, it is likely to be positioned head first.
On the other hand, if the heartbeat is best heard above
the level of the navel, it is likely to be breech.
The only way to really be sure, however, is to do
an ultrasound exam. Using this technique it is very
easy to tell the position of the fetus.

Treatment
If a fetus is in the breech position in the last weeks
of pregnancy, there are three possible courses of
action: Cesarean section, attempted version, or vaginal breech delivery.
Cesarean section is the most common way to deliver a breech baby. This surgical procedure carries
more risk for the mother, but many women prefer to
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take the risk of surgery on themselves rather than let
the baby face the risks of breech delivery.
Version is gaining in popularity. Version is a medical procedure in which the obstetrician tries to turn
the breech fetus to the head first position. Version is
successful more than 50% of the time. However, some
babies who are successfully turned will turn back to
the breech position after the procedure is done.
Some women choose breech vaginal delivery. This
should only be attempted if ultrasound shows that the
fetus is in a favorable breech position. Most babies
will do very well during a breech delivery, but it is
always possible that the fetus will be injured, perhaps
seriously.

Prevention
There is no way to prevent a fetus from settling
into the breech position at the end of pregnancy. A
woman who has had one breech fetus is more likely
than average to have another.
Resources
BOOKS

Cunningham, F. Gary, et al., editors. ‘‘Techniques for
Breech Delivery.’’ In Williams Obstetrics. 20th ed.
Stamford: Appleton & Lange, 1997.

Amy B. Tuteur, MD

Breech presentation see Breech birth
Brill-Zinsser disease see Typhus
Brittle bone disease see Osteogenesis
imperfecta
Broken nose see Nasal trauma

I Bronchiectasis
Definition
Bronchiectasis is a condition in which an area of
the bronchial tubes is permanently and abnormally
widened (dilated), with accompanying infection.

Description
The bronchial tubes are the networks of branching
tubes which deliver air to the tiny sacs of the lungs
(alveoli). In bronchiectasis, the diameter of the bronchi
is unusually large. Examination of the walls of the
661

Bronchiectasis

A version should only be done in a hospital, with
an ultrasound machine used to guide the obstetrician
in turning the fetus. The fetus should be monitored
with a fetal monitor before and after the version. Some
obstetricians give the mother an injection of medication to relax the mother’s uterus and prevent any
contractions.

Bronchiectasis

KEY TERMS
Bronchi—The network of tubular passages which
carry air to the lung and allow air to be expelled
from the lungs.
Cilia—Hair-like projections which line the bronchial tubes (also present in other areas of the body).
Normal cilia beat consistently, sweeping the
bronchi clean of bacteria, viruses, and mucus.

Colorized bronchogram of lungs—right tree has almost no
structure caused by chronic inflammation. (Mehau Kulyk,
Photo Researchers. Reproduced by permission.)

bronchial tubes reveals destruction of the normal structural elements, with replacement by scar tissue. Pus
collects within the bronchi, and the normal flow of
oxygen into the lungs, and carbon dioxide out of the
lungs (air exchange) is impaired. The bronchi show
signs of inflammation, with swelling and invasion by a
variety of immune cells. The inflamed areas show signs
of increased growth of blood vessels. The area of the
lung which should be served by a diseased bronchial
tube is also prone to inflammation and infection.

Causes and symptoms
Prior to the widespread use of immunizations,
bronchiectasis was often the result of a serious infection with either measles or whooping cough. Currently,
viruses that cause influenza (flu) or influenza-like
syndromes, as well as a number of bacteria may precede the development of bronchiectasis. Patients who
have been infected with tuberculosis or the virus which
causes AIDS (HIV or human immunodeficiency virus)
also have an increased chance of bronchiectasis.
A number of pre-existing conditions may cause an
individual to be more susceptible than normal to infection, with increased risk of bronchiectasis developing.
These conditions include disorders of cilia, and
immune disorders.
Cilia are the tiny hairs which usually line the
bronchial tubes. Cilia wave constantly, sweeping the
bronchial tubes clean of bacterial or viral invaders,
and cleaning away excess secretions (mucus, sputum)
which may be produced by the bronchi. When these
cilia are abnormal or absent at birth, various bacterial
or viral invaders may remain in the respiratory tract,
multiply, and cause serious infections.
662

Immune disorders include decreased production
of certain immune chemicals (immunoglobulins)
which usually serve to fight off infection by bacterial
or viral invasion. When these immunoglobulins are
not produced in large enough quantity, bacterial
and viral invaders are not effectively killed off, and
infection occurs.
Other causes of bronchiectasis include an abnormally blocked (obstructed) airway. This can be due to
tumor growth within the bronchial tube, or due to a
child accidentally inhaling a small object which then
blocks off the bronchial tube. People with the disease
called cystic fibrosis (CF) often have their bronchial
tubes obstructed by the thick, sticky mucus which is a
hallmark of CF. Toxic exposures (breathing ammonia, for example) can harm the bronchi, and lead to
bronchiectasis. An extreme allergic response of the
immune system to the presence of certain fungi (especially one called Aspergillus) can also damage the
bronchial tubes enough to result in bronchiectasis.
Symptoms of bronchiectasis include constant
cough and the production of infected sputum (sputum
is a mixture of mucus and pus), which may be bloody.
In some cases, there may be wheezing and shortness of
breath. The constant, low-level of infection may flare,
resulting in increased production of sputum, worsening of the cough, and fever. The area of the lung served
by the affected bronchial tube may become severely
infected, resulting in pneumonia.

Diagnosis
Chest x ray may reveal evidence of bronchiectasis,
and CT scans are particularly good at revealing the
thick, dilated bronchial walls of bronchiectasis.
Sputum will need to be collected and cultured (grown
in a laboratory dish), in order to examine it microscopically for the specific type of organism responsible
for infection. A careful search for other underlying
diseases is important, looking in particular for ciliary
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Treatment
Treatment should involve efforts to resolve any
underlying disorder. Infections will require antibiotics,
obstruction may require the removal of a foreign
object or tumor. Medications are available to help
thin the sputum, so that it can be more effectively
coughed up. Rhythmic clapping on the chest and
back, while the patient assumes a number of positions
(head down, primarily), may help the lungs to drain
more effectively. This is called chest physical therapy,
or percussion and postural drainage.
When a particular area of the lung is constantly
and severely infected, surgery may be needed to
remove it. When bleeding occurs from irritated bronchial tubes and overgrown bronchial blood vessels,
surgery may be required either to remove an area of
the bronchial tube, or to inject the bleeding blood
vessel with a material to stop the bleeding.
In some patients, bronchiectasis eventually leads
to a constantly low level of blood oxygen, despite
other treatments. These patients usually have an associated increase in the size of the right side of their
hearts, along with a decrease in the heart’s ability to
pump blood through the lungs. Some patients with
extremely severe symptoms and disability have been
treated with lung transplantation.

Prognosis
Prognosis varies widely, depending on how widespread or focal the bronchiectasis, and the presence of
other underlying disorders.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York, NY
10019. (800) 586-4872. <http://www.lungusa.org>.

Rosalyn Carson-DeWitt, MD

I Bronchiolitis
Definition
Bronchiolitis is an acute viral infection of the
small air passages of the lungs called the bronchioles.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Bronchiole—A thin air passage in the lung that
branches off a larger airway.
Congenital—A condition that an individual is born
with.

Description
Bronchiolitis is extremely common. It occurs
most often in children between the ages of two and
24 months, with peak infection occurring between
three and six months of age. About 25% of infants
have bronchiolitis during their first year, and 95%
have had the disease by their second birthday. In
temperate climates, bronchiolitis peaks from winter
to late spring. In subtropical climates, the disease
peaks from October to February.
Children who attend daycare or who live in
crowded conditions and those who are exposed to
second-hand smoke at home are more likely to develop
bronchiolitis. Premature infants and children born with
heart and lung defects or HIV/AIDS are more likely to
have severe, life-threatening infections. Bronchiolitis
occurs more often in boys than girls, with boys being
hospitalized at 1.5 times the rate of girls. Bronchiolitis
is a significant cause of respiratory disease worldwide.
The World Health Organization (WHO) has funded
research to develop a vaccine against the disease, but
thus attempts have been unsuccessful.

Causes and symptoms
Bronchiolitis is caused by several different viruses.
The most common of these is respiratory syncytial
virus (RVS), which is responsible for about 100,000
hospitalizations of children under age four each year.
Two subtypes of RSV have been identified, one of
which causes most of the severe bronchiolitis infections. In addition, bronchiolitis can be caused by influenza, parainfluenza, and adenoviruses, all of which are
common from fall through spring. These viruses are
spread in tiny drops of fluid from an infected person’s
nose and mouth through direct contact, such as shaking hands, or kissing. The viruses can also live several
hours on countertops, toys, or used tissues and easily
infect people who handle contaminated items. The
time from infection to the appearance of symptoms
varies from two to seven days.
Bronchiolitis affects individuals differently
depending on their age. In adults, older children, and
663

Bronchiolitis

abnormalities, cystic fibrosis, or immunoglobulin
deficiencies.

Bronchiolitis

some infants, bronchiolitis viruses causes symptoms
similar to a mild cold—runny nose, stuffy head, and
mild cough. The lungs are not involved, and these
symptoms clear up without any medical treatment. In
some children under age two, the cold-like upper
respiratory symptoms worsen after a day or two. The
lung tissue begins to swell and produce mucus, and
the cells lining the bronchioles begin to slough off
into the air passages. As the airways narrow from
swelling, and mucus accumulation, breathing becomes
difficult, and the child makes a wheezing or whistling
sound with each breath. Lung involvement can occur
quite rapidly.
The most common signs of bronchiolitis involve
the infant’s struggle to breathe. The child may take
50–60 breaths per minute and may develop brief periods when they stop breathing (apnea) and begin to
turn blue (cyanosis). This occurs most often in babies
who were born very prematurely or who are under six
weeks of age and babies with congenital heart and lung
problems and compromised immune systems. Babies
may also stop eating, because it is becomes difficult
for them to swallow and breathe at the same time.
They may have a low fever, cough, and vomiting.

Diagnosis
Bronchiolitis is usually diagnosed through a physical examination by a pediatrician or family physician. The physician often finds an increased heart
rate, rapid, labored breathing, and crackles in the
lungs when the child inhales. Signs of ear infection
(otitis media) and throat infection (pharyngitis) are
sometimes present.
Although laboratory tests are available that can
within in a few hours confirm the presence of RSV,
these tests are not routinely necessary. The oxygen
level in the blood may be measured through pulse
oximetry in babies who are having difficulty breathing.
Inadequate oxygen in the blood is an indication that
hospitalization is necessary. Chest x-rays may be done
on severely ill children to rule out other conditions.

Treatment
The degree of respiratory distress determines
treatment. Individuals with mild symptoms are treated
as if they have a cold with rest, fluids, and a cool
air humidifier. Babies who are struggling to breath
may hospitalized and given supplemental humidified
oxygen. Their breathing will be monitored and if
necessary fluids will be given intravenously to prevent
dehydration. Occasionally infants need mechanical
664

ventilation to fill and empty the lungs until the airways
open.
Those children with compromised immune systems from diseases such as congenital HIV/AIDS
and transplant patients are at highest risk for severe
infections, serious complications, and death. Children
with congenital heart and lung disorders are also at
higher risk, as are infants under six weeks old. These
high risk children may be admitted to pediatric intensive care units and treated with ribvarin (Virazole), a
drug that keeps the virus from reproducing. This drug
is reserved for the most critical cases.

Alternative treatment
Although there are alternative treatments for
cold symptoms, such as echinacea and zinc, parents
should consult their health practitioner about the
appropriateness of using these treatments in very
young children.

Prognosis
The majority of children who get bronchiolitis,
even severe infections, recover without complications
in one to two weeks, although fatigue and a light
cough may linger longer. About 60% of people
develop only cold-like symptoms without lung involvement. However, the disease accounts for about
100,000 pediatric hospitalizations and 4,500 deaths
each year. Deaths usually occur because medical care
is not sought soon enough.
Although many viral illnesses, like chicken pox,
can be contracted only once, after which individuals
develop immunity, people can get bronchiolitis multiple times. However, after the first infection, the symptoms are usually mild.

Prevention
The viruses that cause bronchiolitis spread very
easily, making prevention difficult. Common sense
measures such as frequent hand washing and keeping
children away from crowds and sick individuals are
only partially effective. Certain very high risk babies
can be treated during the peak virus season with
monthly injections of antiviral immunoglobulins to
protect against RSV infection. These injections cost
several thousand dollars per child per season and are
reserved for children whose life could be at risk if they
became infected. Antiviral immunoglobulins are used
only for prevention and are not effective as a treatment
once the infection has been acquired.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

OTHER

‘‘Bronchitis.’’ Medline Plus Medical Encyclopedia 19 January
2005 [cited 16 February 2005]. <http://www.nlm.nih.
gov/medlineplus/ency/article/000975.htm>.
DeNicola, Lucian K. and Michael Gayle. Bronchiolitis, 17
July 2003 [cited 16 February 2005]. <http://www.eme
dicine.com/ped/topic287.htm>.
Kirlov, Leonard R. Respiratory Syncytial Virus Infection, 24
November 2004 [cited 16 February 2005]. <http://
www.emedicine.com/ped/topic2706.htm>.
Louden, Mark. Pediatrics, Bronchiolitis, 21 May 2001 [cited
16 February 2005]. <http://www.emedicine.com/
emerg/topic365.htm>.
‘‘Respiratory Syncytial Virus (RSV).’’ Medline Plus Medical
Encyclopedia 19 January 2005 [cited 16 February 2005].
<http://www.nlm.nih.gov/medlineplus/ency/article/
001564.htm>

Tish Davidson, A. M.

I Bronchitis
Definition
Bronchitis is an inflammation of the air passages
between the nose and the lungs, including the windpipe or trachea and the larger air tubes of the lung that
bring air in from the trachea (bronchi). Bronchitis can
either be of brief duration (acute) or have a long course
(chronic). Acute bronchitis is usually caused by a viral
infection, but can also be caused by a bacterial infection and can heal without complications. Chronic
bronchitis is a sign of serious lung disease that may
be slowed but cannot be cured.

Description
Although acute and chronic bronchitis are both
inflammations of the air passages, their causes and
treatments are different. Acute bronchitis is most prevalent in winter. It usually follows a viral infection,
such as a cold or the flu, and can be accompanied by
a secondary bacterial infection. Acute bronchitis
resolves within two weeks, although the cough may
persist longer. Acute bronchitis, like any upper airway
inflammatory process, can increase a person’s likelihood of developing pneumonia.
Anyone can get acute bronchitis, but infants,
young children, and the elderly are more likely to get
the disease because people in these age groups generally
GALE ENCYCLOPEDIA OF MEDICINE

Acute—Disease or condition characterized by the
rapid onset of severe symptoms.
Bronchi—The larger air tubes of the lung that bring
air in from the trachea.
Chronic—Disease or condition characterized by
slow onset over a long period of time.
Chronic obstructive pulmonary disease (COPD)—
A term used to describe chronic lung diseases, like
chronic bronchitis, emphysema, and asthma.
Emphysema—One of the several diseases called
chronic obstructive pulmonary diseases, emphysema involves the destruction of air sac walls to
form abnormally large air sacs that have reduced
gas exchange ability and that tend to retain air
within the lungs. Symptoms include labored
breathing, the inability to forcefully blow air out
of the lungs, and an increased susceptibility to
respiratory tract infections.

have weaker immune systems. Smokers and people
with heart or other lung diseases are also at higher
risk of developing acute bronchitis. Individuals exposed
to chemical fumes or high levels of air pollution also
have a greater chance of developing acute bronchitis.
Chronic bronchitis is a major cause of disability
and death in the United States. The American Lung
Association estimates that about 14 million Americans
suffer from the disease. Like acute bronchitis, chronic
bronchitis is an inflammation of airways accompanied by coughing and spitting up of phlegm. In
chronic bronchitis, these symptoms are present for
at least three months in each of two consecutive
years.
Chronic bronchitis is caused by inhaling bronchial
irritants, especially cigarette smoke. Until recently,
more men than women developed chronic bronchitis,
but as the number of women who smoke has
increased, so has their rate of chronic bronchitis.
Because this disease progresses slowly, middle-aged
and older people are more likely to be diagnosed
with chronic bronchitis.
Chronic bronchitis is one of a group of diseases
that fall under the name chronic obstructive pulmonary disease (COPD). Other diseases in this category
include emphysema and chronic asthmatic bronchitis.
Chronic bronchitis may progress to emphysema, or
both diseases may be present together.
665

Bronchitis

Resources

Bronchitis

Causes and symptoms
Acute bronchitis
Acute bronchitis usually begins with the symptoms of a cold, such as a runny nose, sneezing, and
dry cough. However, the cough soon becomes deep
and painful. Coughing brings up a greenish yellow
phlegm or sputum. These symptoms may be accompanied by a fever of up to 102  F (38.8  C). Wheezing
after coughing is common.
In uncomplicated acute bronchitis, the fever and
most other symptoms, except the cough, disappear
after three to five days. Coughing may continue for
several weeks. Acute bronchitis is often complicated
by a bacterial infection, in which case the fever and a
general feeling of illness persist. To be cured, the
bacterial infection should be treated with antibiotics.
Chronic bronchitis
Chronic bronchitis is caused by inhaling respiratory tract irritants. The most common irritant is
cigarette smoke. The American Lung Association
estimates that 80-90% of COPD cases are caused by
smoking. Other irritants include chemical fumes, air
pollution, and environmental irritants, such as mold
or dust.
Chronic bronchitis develops slowly over time. The
cells that line the respiratory system contain fine, hairlike outgrowths from the cell called cilia. Normally,
the cilia of many cells beat rhythmically to move
mucus along the airways. When smoke or other irritants are inhaled, the cilia become paralyzed or snap
off. When this occurs, the cilia are no longer able to
move mucus, and the airways become inflamed, narrowed, and clogged. This leads to difficulty breathing
and can progress to the life-threatening disease
emphysema.
A mild cough, sometimes called smokers’ cough, is
usually the first visible sign of chronic bronchitis.
Coughing brings up phlegm, although the amount varies considerably from person to person. Wheezing and
shortness of breath may accompany the cough.
Diagnostic tests show a decrease in lung function. As
the disease advances, breathing becomes difficult and
activity decreases. The body does not get enough oxygen, leading to changes in the composition of the blood.

Diagnosis
Initial diagnosis of bronchitis is based on observing
the patient’s symptoms and health history. The physician will listen to the patient’s chest with a stethoscope
666

for specific sounds that indicate lung inflammation,
such as moist rales and crackling, and wheezing, that
indicates airway narrowing. Moist rales is a bubbling
sound heard with a stethoscope that is caused by fluid
secretion in the bronchial tubes.
A sputum culture may be performed, particularly
if the sputum is green or has blood in it, to determine
whether a bacterial infection is present and to identify
the disease-causing organism so that an appropriate
antibiotic can be selected. Normally, the patient will
be asked to cough deeply, then spit the material that
comes up from the lungs (sputum) into a cup. This
sample is then grown in the laboratory to determine
which organisms are present. The results are available
in two to three days, except for tests for tuberculosis,
which can take as long as two months.
Occasionally, in diagnosing a chronic lung disorder, the sample of sputum is collected using a procedure called a bronchoscopy. In this procedure, the
patient is given a local anesthetic, and a tube is passed
into the airways to collect a sputum sample.
A pulmonary function test is important in diagnosing chronic bronchitis and other variations of COPD.
This test uses an instrument called a spirometer to
measure the volume of air entering and leaving the
lungs. The test is done in the doctor’s office and is
painless. It involves breathing into the spirometer
mouthpiece either normally or forcefully. Volumes
less than 80% of the normal values indicate an
obstructive lung disease.
To better determine what type of obstructive lung
disease a patient has, the doctor may do a chest x ray,
electrocardiogram (ECG), and blood tests. An electrocardiogram is an instrument that is used to measure
the electrical activity of the heart and is useful in the
diagnosis of heart conditions. Other tests may be used
to measure how effectively oxygen and carbon dioxide
are exchanged in the lungs.

Treatment
Acute bronchitis
When no secondary infection is present, acute
bronchitis is treated in the same way as the common
cold. Home care includes drinking plenty of fluids,
resting, not smoking, increasing moisture in the air
with a cool mist humidifier, and taking acetaminophen
(Datril, Tylenol, Panadol) for fever and pain. Aspirin
should not be given to children because of its association with the serious illness, Reye’s syndrome.
Expectorant cough medicines, unlike cough suppressants, do not stop the cough. Instead they are used
GALE ENCYCLOPEDIA OF MEDICINE

If a secondary bacterial infection is present, the
infection is treated with an antibiotic. Patients need
to take the entire amount of antibiotic prescribed.
Stopping the antibiotic early can lead to a return of the
infection. Tetracycline or ampicillin are often used to
treat adults. Other possibilities include trimethoprim/
sulfamethoxazole (Bactrim or Septra) and the newer
erythromycin-like drugs, such as azithromycin
(Zithromax) and clarithromycin (Biaxin). Children
under age eight are usually given amoxicillin (Amoxil,
Pentamox, Sumox, Trimox), because tetracycline discolors permanent teeth that have not yet come in.
Chronic bronchitis
The treatment of chronic bronchitis is complex
and depends on the stage of chronic bronchitis and
whether other health problems are present. Lifestyle
changes, such as quitting smoking and avoiding secondhand smoke or polluted air, are an important first
step. Controlled exercise performed on a regular basis
is also important.
Drug therapy begins with bronchodilators. These
drugs relax the muscles of the bronchial tubes and
allow increased air flow. They can be taken by mouth
or inhaled using a nebulizer. A nebulizer is a device that
delivers a regulated flow of medication into the airways.
Common bronchodilators include albuterol (Ventolin,
Proventil, Apo-Salvent) and metaproterenol (Alupent,
Orciprenaline, Metaprel, Dey-Dose).
Anti-inflammatory medications are added to
reduce swelling of the airway tissue. Corticosteroids,
such as prednisone, can be taken orally or intravenously. Other steroids are inhaled. Long-term steroid
use can have serious side effects. Other drugs, such as
ipratropium (Atrovent), are given to reduce the quantity of mucus produced.
As the disease progresses, the patient may need
supplemental oxygen. Complications of COPD are
many and often require hospitalization in the latter
stages of the disease.

Alternative treatment
Alternative practitioners focus on prevention by
eating a healthy diet that strengthens the immune
system and practicing stress management. Bronchitis
GALE ENCYCLOPEDIA OF MEDICINE

can become serious if it progresses to pneumonia,
therefore, antibiotics may be required. In addition,
however, there are a multitude of botanical and herbal
medicines that can be formulated to treat bronchitis.
Some examples include inhaling eucalyptus or other
essential oils in warm steam. Herbalists recommend a
tea made of mullein (Verbascum thapsus), coltsfoot
(Tussilago farfara), and anise seed (Pimpinella anisum). Homeopathic medicine and traditional Chinese
medicine may also be very useful for bronchitis, and
hydrotherapy can contribute to cleaning the chest and
stimulating immune response.

Prognosis
When treated, acute bronchitis normally resolves
in one to two weeks without complications, although
a cough may continue for several more weeks. The
progression of chronic bronchitis, on the other hand,
may be slowed, and an initial improvement in symptoms may be achieved. Unfortunately, however,
there is no cure for chronic bronchitis, and the disease
can often lead to or coexist with emphysema. Taken
together, all forms of COPD are a leading cause of
death.

Prevention
The best way to prevent bronchitis is not to begin
smoking or to stop smoking. Smokers are ten times
more likely to die of COPD than non-smokers.
Smokers who stop show improvement in lung function. Other preventative steps include avoiding
chemical and environmental irritants, such as air
pollution, and maintaining good overall health.
Immunizations against certain types of pneumonia
(as well as influenza) are an important preventative
measure for anyone with lung or immune system
diseases.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Jewish Center for Immunology and Respiratory
Medicine. 1400 Jackson St., Denver, CO 80206. (800)
222-5864. <http://www.nationaljewish.org/
main.html>.

Tish Davidson, A.M.
667

Bronchitis

to thin the mucus in the lungs, making it easier to
cough up. This type of cough medicine may be helpful
to individuals suffering from bronchitis. People who
are unsure about what type of medications are in overthe-counter cough syrups should ask their pharmacist
for an explanation.

Bronchodilators

I Bronchodilators
Definition
Bronchodilators are medicines that help open the
bronchial tubes (airways) of the lungs, allowing more
air to flow through them.

Purpose
People with asthma have trouble breathing, because
their airways are inflamed and become narrowed.
Normally, air moves smoothly from the mouth and
nose through the airways and into the tiny air sacs of
the lungs as a person breathes in. Breathing out (exhaling) happens automatically when the person stops
breathing in. In a person with asthma, breathing in
(inhaling) is not a problem. Incoming air can slide
around the blockage, because the act of breathing in
makes the airways expand. The problem comes when
the person with asthma tries to breathe out. The air can
no longer get past the blockage, and it remains trapped
in the lungs. The person can then only take shallow
breaths. Bronchodilators work by relaxing the smooth
muscles that line the airways. This makes the airways
open wider and allows air to leave the lungs. These drugs
also are used to relieve breathing problems associated
with emphysema, chronic bronchitis, and other lung
diseases.

Description
Some bronchodilators are inhaled, using a nebulizer
or an inhalation aerosol. Others are taken as injections
or by mouth. Most are available only by prescription,
but a few, such as ephedrine, can be bought without
a physician’s prescription. Examples of bronchodilators are albuterol (Proventil, Ventolin), epinephrine
(Primatene), ipratropium (Atrovent), metaproterenol
(Alupent, Metaprel), and terbutaline (Brethine).

Recommended dosage
The recommended dosage depends on the type of
bronchodilator and may be different for different
patients. The physician who prescribed the drug or
the pharmacist who filled the prescription can recommend correct dosage.

Precautions
Bronchodilators come with patient instructions
that must be carefully read before using the medicine.
If there is any confusion about how to use the
668

KEY TERMS
Anti-inflammatory—Medicine used to relieve swelling, pain, and other symptoms of inflammation.
Bronchitis—Inflammation of the air passages of the
lungs.
Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop
gradually and involve slow changes.
Emphysema—A lung disease in which breathing
becomes difficult.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Nebulizer—A device that turns liquid forms of
medicine into a fine spray that can be inhaled.
Sulfite—A type of preservative that causes allergic
reactions in some people.

medicine, patients should check with the physician or
pharmacist. These medicines must be used exactly as
directed. Taking larger than recommended doses or
using the medicine too often can lead to serious side
effects and even death.
If symptoms do not improve or if they get worse
after using a bronchodilator, the patient should call a
physician right away.
Although some bronchodilators are available
without a physician’s prescription, these medicines
should not be used unless a physician has diagnosed
the patient’s condition as asthma.
Research shows that frequent bronchodilator use
over time can tighten airway muscles in some people.
Some physicians advise patients to consider controlling asthma with anti-inflammatory drugs including
inhaled steroids such as beclomethasone dipropionate
(Beclovent, Vanceril), flunisolide (AeroBid) or triamcinolone acetonide (Azmacort). A 2004 Canadian study
has questioned a standard practice of increasing steroids
after asthma attacks or worsened symptoms. Also,
research in 2004 showed that people with asthma who
worked closely with their physicians to self-manage
their asthma had fewer attacks, which reduces the need
for bronchodilators. Carefully managing asthma also
reduces visits to the emergency department and
hospitalizations.
Persons with diabetes should be aware that the
bronchodilator epinephrine may raise their blood
sugar levels.
GALE ENCYCLOPEDIA OF MEDICINE

OTHER MEDICAL CONDITIONS. Before using
bronchodilators, people with any of these medical
problems should make sure their physicians are
aware of their conditions:

Some bronchodilator products contain sulfites
that trigger an allergic reaction in certain people.
Anyone who has a sulfite allergy should read the
label carefully or check with a physician or pharmacist
before using a bronchodilator. Call a physician immediately if any of these signs of an allergic reaction to
sulfite occur:


bluish coloration of the skin



flushed or red face or skin



faintness



severe dizziness



increased wheezing or other breathing problems



skin rash, hives, or itching



swelling of the face, lips, or eyelids



glaucoma



brain damage



convulsions (seizures)—recently or anytime in the
past



mental illness



parkinson’s disease



diabetes



heart or blood vessel diseases



rapid or irregular heartbeat



high blood pressure



overactive thyroid



enlarged prostate



obstruction of the neck of the bladder

USE OF CERTAIN MEDICINES. Using bronchodilators with certain other drugs may affect the way the
drugs work or may increase the chance of side effects.

Side effects
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they use bronchodilators. Before using these drugs, a
physician should be made aware of any of these
conditions:
ALLERGIES. Anyone who has had unusual reactions to any bronchodilator or an inhaled form of
any other drug in the past should let his or her physician know before taking the drugs again. The physician should also be told about any allergies to foods,
dyes, preservatives, or other substances.

Patients who are allergic to soybeans, soy lecithin,
peanuts, or drugs based on atropine should not use the
bronchodilator ipratropium (Atrovent).
PREGNANCY. In studies of laboratory animals,

some bronchodilators cause birth defects or miscarriage when the animals are given doses many times
the usual human dose. Whether these drugs cause such
problems in humans in unknown. Any woman who is
pregnant or plans to become pregnant should check
with her physician before using a bronchodilator.

Some patients have a dry or irritated throat or a
dry mouth after using bronchodilators. To help prevent these problems, gargling and rinsing the mouth or
taking a sip of water after each dose.
The most common side effects are nervousness or
restlessness and trembling. These problems usually go
away as the body adjusts to the drug and do not
require medical treatment. Less common side effects,
such as bad taste in the mouth, coughing, dizziness or
lightheadedness, drowsiness, headache, sweating, fast
or pounding heartbeat, muscle cramps or twitches,
nausea, vomiting, diarrhea, sleep problems and weakness also may occur and do not need medical attention
unless they do not go away or they interfere with
normal activities.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
the physician who prescribed the medicine should be
contacted as soon as possible:


chest pain or discomfort



irregular or fluttery heartbeat



unusual bruising



hives or rash



swelling

BREASTFEEDING. Some bronchodilators pass into

breast milk. Breastfeeding mothers should check with
their physicians before using bronchodilators.
GALE ENCYCLOPEDIA OF MEDICINE

669

Bronchodilators

Patients who are using an aerosol bronchodilator
and an aerosol form of either ipratropium or a corticosteroid such as beclomethasone dipropionate
(Beclovent, Vanceril) should use the bronchodilator
first, then wait 5 minutes before using the other medicine. A physician should be consulted before using
any other inhaled medications or other asthma medicines. The physician must determine the proper
amount of time between doses.

Bronchoscopy



wheezing or other breathing problems

ORGANIZATIONS



numbness in the hands or feet



blurred vision

American Academy of Allergy, Asthma, and Immunology.
611 East Wells St., Milwaukee, WI 53202. (800) 8222762. <http://www.aaaai.org>.
Asthma and Allergy Foundation of America. 1233 20th
Street, NW, Suite 402, Washington, DC 20036. (800)
727-8462. <http://www.aafa.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Other side effects are possible. Anyone who has
unusual symptoms after using a bronchodilator
should get in touch with his or her physician.

Interactions
Bronchodilators may interact with a number of
other medicines. When this happens, the effects of one
or both of the drugs may change or the risk of side
effects may be greater. Anyone who takes these drugs
should let the physician know all other medicines he or
she is taking. Among the drugs that may interact with
bronchodilators are:


monoamine oxidase inhibitors (MAO inhibitors)
such as phenelzine (Nardil) and tranylcypromine
(Parnate), used to treat depression



other bronchodilators



tricyclic antidepressants such as amitriptyline
(Elavil) and imipramine (Tofranil)



beta blockers such as propranolol (Inderal) and
atenolol (Tenormin), used to control high blood
pressure



digitalis medicines, used to treat heart conditions,
such as digoxin (Lanoxin)



drugs, such as certain diuretics (water pills), that
lower potassium levels



ergoloid mesylates such as Hydergine, used to treat
symptoms of Alzheimer’s disease or multiple small
stokes



ergotamine (Cafergot, Ergostat, and other brands),
used to treat migraine and cluster headaches



the antidepressant maprotiline (Ludiomil).

The list above does not include every drug that
may interact with bronchodilators. Be sure to check
with a physician or pharmacist before combining
bronchodilators with any other prescription or nonprescription (over-the-counter) medicine.
Resources
PERIODICALS

‘‘Study Calls Standard Asthma Management Into Doubt.’’
Doctor July 15, 2004: 4.
‘‘What’s New in: Asthma and Allergic Rhinitis.’’ Pulse
September 20, 2004: 50.
‘‘Wheezing? Check Your Inhaler.’’ Prevention September
2004: 34.
670

Nancy Ross-Flanigan
Teresa G. Odle

I Bronchoscopy
Definition
Bronchoscopy is a procedure in which a cylindrical fiberoptic scope is inserted into the airways. This
scope contains a viewing device that allows the visual
examination of the lower airways.

Purpose
During a bronchoscopy, a physician can visually
examine the lower airways, including the larynx, trachea, bronchi, and bronchioles. The procedure is used
to examine the mucosal surface of the airways for
abnormalities that might be associated with a variety
of lung diseases. Its use includes the visualization of
airway obstructions such as a tumor, or the collection
of specimens for the diagnosis of cancer originating in
the bronchi of the lungs (bronchogenic cancer). It can
also be used to collect specimens for culture to diagnose infectious diseases such as tuberculosis. The type
of specimens collected can include sputum (composed
of saliva and discharges from the respiratory passages), tissue samples from the bronchi or bronchioles,
or cells collected from washing the lining of the
bronchi or bronchioles. The instrument used in
bronchoscopy, a bronchoscope, is a slender cylindrical
instrument containing a light and an eyepiece. There
are two types of bronchoscopes, a rigid tube that is
sometimes referred to as an open-tube or ventilating
bronchoscope, and a more flexible fiberoptic tube.
This tube contains four smaller passages—two for
light to pass through, one for seeing through and one
that can accommodate medical instruments that may
be used for biopsy or suctioning, or that medication
can be passed through.
GALE ENCYCLOPEDIA OF MEDICINE

Anesthesia—A drug used to loss of sensation. It is used
to lessen the pain of surgery and medical procedures.
Bronchi—The network of tubular passages that
carry air to the lungs and allow air to be expelled
from the lungs.
Bronchioles—Small airways extending from the
bronchi into the lobes of the lungs.
Bronchoalveolar lavage—Washing cells from the
air sacs at the end of the bronchioles.
Instruments used in bronchoscopy procedures. (Custom
Medical Stock Photo. Reproduced by permission.)

Bronchoscopy may be used for the following
purposes:


to diagnose cancer, tuberculosis, lung infection, or
other lung disease



to examine an inherited deformity of the lungs



to remove a foreign body in the lungs, such as a
mucus plug, tumor, or excessive secretions



to remove tissue samples, also known as biopsy, to test
for cancer cells, help with staging the advancement of
the lung cancer, or to treat a tumor with laser therapy



to allow examination of a suspected tumor, obstruction, secretion, bleeding, or foreign body in the airways



to determine the cause of a persistent cough, wheezing, or a cough that includes blood in the sputum



to evaluate the effectiveness of lung cancer treatments

Precautions
Patients not breathing adequately on their own
due to severe respiratory failure may require mechanical ventilation prior to bronchoscopy. It may not be
appropriate to perform bronchoscopy on patients
with an unstable heart condition. All patients must
be constantly monitored while undergoing a bronchoscopy so that any abnormal reactions can be dealt with
immediately.

Trachea—The windpipe.

rigid tube must be used because of its larger size. The
patient will either lie face-up on his/her back or sit
upright in a chair. Medication to decrease secretions,
lessen anxiety, and relax the patient are often given
prior to the procedure. While breathing through the
nose, anesthesia is sprayed into the mouth or nose to
numb it. It will take one to two minutes for the
anesthesia to take effect. Once this happens, the
bronchoscope will be put into the patient’s mouth or
nose and moved down into the throat. While the
bronchoscope is moving down the throat, additional
anesthesia is put into the bronchoscope to numb the
lower parts of the airways. Using the eyepiece, the
physician then observes the trachea and bronchi, and
the mucosal lining of these passageways, looking for
any abnormalities that may be present.
If the purpose of the bronchoscopy is to take
tissue samples or biopsy, forceps or a bronchial
brush are used to obtain cells. If the purpose is to
identify an infectious agent, a bronchoalveolar lavage
(BAL) can be used to gather fluid for culture purposes.
Also, if any foreign matter is found in the airways, it
can be removed.
Another procedure using bronchoscopy is called
fluorescence bronchoscopy. This can be used to detect
precancerous cells present in the airways. By using a
fluorescent light in the bronchoscope, precancerous tissue will appear dark red, while healthy tissue will appear
green. This technique can help detect lung cancer at
an early stage, so that treatment can be started early.

Description
There are two types of bronchoscopes, a rigid tube
and a fiberoptic tube. Because of its flexibility, the
fiberoptic tube is usually preferred. However, if the
purpose of the procedure is to remove a foreign body
caught in the windpipe or lungs of a child, the more
GALE ENCYCLOPEDIA OF MEDICINE

Alternative procedures
Depending upon the purpose of the bronchoscopy,
alternatives might include a computed tomography
scan (CT) or no procedure at all. Bronchoscopy is
often performed to investigate an abnormality that
671

Bronchoscopy

KEY TERMS

Bronchoscopy

shows up on a chest x ray or CT scan. If the purpose is
to obtain biopsy specimens, one option is to perform
surgery, which carries greater risks. Another option is
percutaneous (through the skin) biopsy guided by computed tomography.

Bronchoscope

Preparation
The doctor should be informed of any allergies and
all the medications that the patient is currently taking.
The doctor may instruct the patient not to take medications like aspirin or anti-inflammatory drugs, which
interfere with clotting, for a period of time prior to the
procedure. The patient needs to fast for 6 to 12 hours
prior to the procedure and refrain from drinking any
liquids the day of the procedure. The bronchoscopy
takes about 45 to 60 minutes, with results usually available in one day. Prior to the bronchoscopy, several tests
may be done, including a chest x ray and blood work.
Sometimes a bronchoscopy is done under general
anesthesia. Patients usually have an intravenous (IV)
line in the arm. Most likely, the procedure will be done
under local anesthesia, which is sprayed into the nose or
mouth. This is necessary to decrease the gag reflex. A
sedative may also be used to help the patient relax. It is
important that the patient understands that at no time
will the airway be blocked and that oxygen can be
supplied through the bronchoscope. A signed consent
form is necessary for this procedure.

Aftercare
After the bronchoscopy, the patient will be monitored for vital signs such as heart rate, blood pressure,
and breathing, while resting in bed. Sometimes
patients have an abnormal reaction to anesthesia. All
saliva should be spit into a basin so that it can be
examined for the presence of blood. If a biopsy was
taken, the patient should not cough or clear the throat
as this might dislodge any blood clot that has formed
and cause bleeding. No food or drink should be consumed for about two hours after the procedure or until
the anesthesia wears off. Diet is gradually progressed
from ice chips and clear liquids to the patient’s regular
diet. There will also be a temporary sore throat and
hoarseness that may last for a few days.

Risks
Minor side effects arise from the bronchoscope
causing abrasion of the lining of the airways. This
results in some swelling and inflammation, as well as
hoarseness caused from abrading the vocal cords. If
this abrasion is more serious, it can lead to respiratory
672

Bronchoscopy is a procedure in which a hollow, flexible tube
is inserted into the airways, allowing the physician to visually
examine the lower airways, including the larynx, trachea,
bronchi, and bronchioles. It can also be used to collect specimens for bacteriological culture to diagnose infectious
diseases such as tuberculosis. (Illustration by Electronic
Illustrators Group.)

difficulty or bleeding of the airway lining. A more
serious risk involved in having a bronchoscopy performed is the occurrence of a pneumothorax, due to
puncturing of the lungs, which allows air to escape
into the space between the lung and the chest wall.
These risks are greater with the use of a rigid bronchoscope than with a fiberoptic bronchoscope. If a rigid
tube is used, there is also a risk of chipped teeth.

Normal results
Normal tracheal appearance consists of smooth
muscle with C-shaped rings of cartilage at regular
intervals. The trachea and the bronchi are lined with
a mucous membrane.

Abnormal results
Abnormal bronchoscopy findings may involve
abnormalities of the bronchial wall such as
GALE ENCYCLOPEDIA OF MEDICINE

Cindy L. Jones, Ph.D.

I Brucellosis
Definition
Brucellosis is a bacterial disease caused by members of the Brucella genus that can infect humans but
primarily infects livestock. Symptoms of the disease
include intermittent fever, sweating, chills, aches, and
mental depression. The disease can become chronic
and recur, particularly if untreated.

Description
Also known as undulant fever, Malta fever,
Gibraltar fever, Bang’s disease, or Mediterranean
fever, brucellosis is most likely to occur among those
individuals who regularly work with livestock. The
disease originated in domestic livestock but was
passed on to wild animal species, including the elk
and buffalo of the western United States. In humans,
brucellosis continues to be spread via unpasteurized
milk obtained from infected cows or through contact
with the discharges of cattle and goats during
miscarriage. In areas of the world where milk is not
pasteurized, for example in Latin America and the
Mediterranean, the disease is still contracted by ingesting unpasteurized dairy products. However, in the
United States, the widespread pasteurization of milk
and nearly complete eradication of the infection from
cattle has reduced the number of human cases from
6,500 in 1940 to about 70 in 1994.

Causes and symptoms
The disease is caused by several different species
of parasitic bacteria of the genus Brucella. B. abortus is
found in cattle and can cause cows to abort their
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Chronic—Disease or condition characterized by
slow onset over a long period of time.
Parasite—An organism living in or on, and obtaining nourishment from, another organism.
Pasteurization—The process of applying heat,
usually to milk or cheese, for the purpose of killing,
or retarding the development of, pathogenic bacteria.

fetuses. B. suis is most often found in hogs and is
more deadly when contracted by humans than the
organism found in cattle. B. melitensis is found in
goats and sheep and causes the most severe illness in
humans. B. rangiferi infects reindeer and caribou, and
B. canis is found in dogs.
A human contracts the disease by coming into
contact with an infected animal and either allowing
the bacteria to enter a cut, breathing in the bacteria, or
by consuming unpasteurized milk or fresh goat cheese
obtained from a contaminated animal. In the United
States, the disease is primarily confined to slaughterhouse workers.
Scientists do not agree about whether brucellosis can be transmitted from one person to another,
although some people have been infected from a
tainted blood transfusion or bone marrow transplant. Newborn babies have also contracted the illness from their mothers during birth. Currently, it is
believed that brucellosis can also be transmitted
sexually.
The disease is not usually fatal, but the intermittent fevers (a source of its nickname, ‘‘undulant
fever’’) can be exhausting. Symptoms usually appear
between five days and a month after exposure and
begin with a single bout of high fever accompanied
by shivering, aching, and drenching sweats that last
for a few days. Other symptoms may include headache,
poor appetite, backache, weakness, and depression.
Mental depression can be so severe that the patient
may become suicidal.
In rare, untreated cases, the disease can become so
severe that it leads to fatal complications, such as
pneumonia or bacterial meningitis. B. melitensis can
cause miscarriages, especially during the first three
months of pregnancy. The condition can also occur
673

Brucellosis

inflammation, swelling, ulceration, or anatomical
abnormalities. The bronchoscopy may also reveal the
presence of abnormal substances in the trachea and
bronchi. If samples are taken, the results could indicate cancer, disease-causing agents or other lung disease. Other abnormalities include constriction or
narrowing (stenosis), compression, dilation of vessels,
or abnormal branching of the bronchi. Abnormal substances that might be found in the airways include
blood, secretions, or mucous plugs. Any abnormalities
are discussed with the patient.

Bruises

in a chronic form, in which symptoms recur over a
period of months or years.

Centers for Disease Control. <http://www.cdc.gov/
nccdphp/ddt/ddthome.htm>.

Carol A. Turkington

Diagnosis
Brucellosis is usually diagnosed by detecting one
or more Brucella species in blood or urine samples.
The bacteria may be positively identified using biochemical methods or using a technique whereby, if
present in the sample, the brucellosis bacteria are
made to fluoresce. Brucellosis may also be diagnosed
by culturing and isolating the bacteria from one of the
above samples. Blood samples will also indicate elevated antibody levels or increased amounts of a protein produced directly in response to infection with
brucellosis bacteria.

Treatment
Prolonged treatment with antibiotics, including
tetracyclines (with streptomycin), co-trimoxazole,
and sulfonamides, is effective. Bed rest is also imperative. In the chronic form of brucellosis, the symptoms
may recur, requiring a second course of treatment.

Prognosis
Early diagnosis and prompt treatment is essential
to prevent chronic infection. Untreated, the disease
may linger for years, but it is rarely fatal. Relapses
may also occur.

Prevention
There is no human vaccine for brucellosis, but
humans can be protected by controlling the disease in
livestock. After checking to make sure an animal is not
already infected, and destroying those that are, all livestock should be immunized. Butchers and those who
work in slaughterhouses should wear protective glasses
and clothing, and protect broken skin from infection.
Some experts suggest that a person with the disease
refrain from engaging in unprotected sex until free of
the disease. The sexual partners of an infected person
should also be closely monitored for signs of infection.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
OTHER

‘‘Bacterial Diseases.’’ Healthtouch Online Page.
<http:www.healthtouch.com>.
674

Brugian filariasis see Elephantiasis

I Bruises
Definition
Bruises, or ecchymoses, are a discoloration and
tenderness of the skin or mucous membranes due
to the leakage of blood from an injured blood vessel
into the tissues. Pupura refers to bruising as the result of
a disease condition. A very small bruise is called
a petechia. These often appear as many tiny red dots
clustered together, and could indicate a serious problem.

Description
Bruises change colors over time in a predictable
pattern, so that it is possible to estimate when an injury
occurred by the color of the bruise. Initially, a bruise
will be reddish, the color of the blood under the skin.
After one to two days, the red blood cells begin to break
down, and the bruise will darken to a blue or purplish
color. This fades to green at about day six. Around the
eighth or ninth day, the skin over the bruised area
will have a brown or yellowish appearance, and it will
gradually diminish back to its normal color.
Long periods of standing will cause the blood that
collects in a bruise to seep through the tissues. Bruises
are actually made of little pools of blood, so the blood
in one place may flow downhill after awhile and
appear in another. For instance, bruising in the back
of the abdomen may eventually appear in the groin;
bruising in the thigh or the knee will work its way
down to the ankle.

Causes and symptoms
Healthy people may develop bruises from any
injury that doesn’t break through the skin. Vigorous
exercise may also cause bruises due to bringing about
small tears in blood vessels walls. In a condition
known as purpura simplex, there is a tendency to
bruise easily due to an increased fragility of the
blood vessels. Bruises also develop easily in the elderly,
because the skin and blood vessels have a tendency to
become thinner and more fragile with aging, and there
is an increased use of medications that interfere with
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
A bruise by itself needs no medical treatment. It is
often recommended that ice packs be applied on and off
during the first 24 hours of injury to reduce the bruising.
After that, heat, especially moist heat, is recommended
to increase the circulation and the healing of the injured
tissues. Rest, elevation of the effected part, and compression with a bandage will also retard the accumulation of blood. Rarely, if a bruise is so large that the body
cannot completely absorb it or if the site becomes
infected, it may have to be surgically removed.
A close-up view of woman’s bruised left eye. (Custom Medical
Stock Photo. Reproduced by permission.)

the blood clotting system. In the condition known as
purpura senilis, the elderly develop bruises from minimal contact that may take up to several months to
completely heal.
The use of nonsteroidal anti-inflammatories such
as ibuprofen (Advil) and naproxen (Aleve) may lead to
increasedbruising. Aspirin, antidepressants, asthma medications, and cortisone medications also have this effect.
The anti-clotting medications also known as blood
thinners, especially the drug Warfarin (Coumadin),
may be the cause of particularly severe bruising.
Sometimes bruises are connected with more serious
illnesses. There are a number of diseases that cause
excessive bleeding or bleeding from injuries too slight
to have consequences in healthy people. An abnormal
tendency to bleed may be due to hereditary bleeding
disorders, certain prescription medications, diseases of
the blood such as leukemia, and diseases that increase
the fragility of blood vessels. If there are large areas of
bruising or bruises develop very easily, this may herald
a problem. Other causes that should be ruled out
include liver disease, alcoholism, drug addiction, and
acquired immune deficiency syndrome (AIDS).
Bruising that occurs around the navel may indicate
dangerous internal bleeding; bruising behind the ear,
called Battle’s sign, may be due to a skull fracture; and
raised bruises may point to autoimmune disease.

Alternative treatment
Several types of topical applications are usually
recommend to speed healing and to reduce the pain
associated with bruises. Vitamin K cream can be
applied directly to the site of injury. Astringent herbs
such as witch hazel, Hamamelis virginiana, can be used.
This will tighten the tissues and therefore diminish the
bruising. The homeopathic remedy, Arnica montana,
can be applied as a cream or gel to unbroken skin.
Oral homeopathic remedies may reduce bruising,
pain, and swelling as well. Arnica montana, at 30 ml
(1 oz), taken one to two times per day is highly recommended. For ledum, 30 ml (1 oz) one to two times per
day is also useful.

Prognosis
The blood under the skin which causes the discoloration of bruising should be totally reabsorbed by
the body in three weeks or less. At that time, the skin
color should completely return to normal.
Sometimes, a bruise may become solid and
increase in size instead of dissolving. This may indicate blood trapped in the tissues, which may be need
to be drained. This is referred to as a hematoma.
Less commonly, the body may develop calcium
deposits at the injury site in a process called heterotopic ossification.

Prevention
Diagnosis
Bruising is usually a minor problem, which does
not require a medical diagnosis. However, faced with
extensive bruising, bruising with no apparent cause, or
bruising in certain locations, a physician will pursue an
GALE ENCYCLOPEDIA OF MEDICINE

Vitamin K promotes normal clotting in the
blood, and therefore may help reduce the tendency
to bruise easily. Green leafy vegetables, alfalfa, broccoli, seaweed, and fish liver oils are dietary sources of
vitamin K. Other good foods to eat would be those
675

Bruises

evaluation that will include a number of blood tests. If
the area of the bruise becomes hard, an x ray may be
required.

Bruxism

containing bioflavonoids, such as reddish-blue berries. These can assist in strengthening the connective
tissue, which will decrease the spread of blood and
bruising. Zinc and vitamin C supplements are also
recommended for this.
Resources
BOOKS

KEY TERMS
Enamel—The hard outermost surface of a tooth.
High spot—An area of a tooth or restoration that
feels abnormal or uncomfortable because it hits its
opposing tooth before other teeth meet.

Editors of Prevention Magazine Health Books, editors. The
Doctors Book of Home Remedies. Prevention Health
Books, 2000.

Night guard—A removable, custom-fitted plastic
appliance that fits between the upper and lower
teeth to prevent them from grinding against each
other.

Patience Paradox

Occlusion—The way upper and lower teeth fit
together during biting and chewing.

Bruton’s agammaglobulinemia see X-linked
agammaglobulinemia

Rolfing—Based on the belief that proper alignment
of various parts of the body is necessary for physical
and mental health, rolfing uses deep tissue massage
and movement exercises in an attempt to bring the
body into correct alignment.

I Bruxism

Temporomandibular joint (TMJ)—The jaw joint
formed by the mandible (lower jaw bone) moving
against the temporal bone of the skull.

Definition
Bruxism is the habit of clenching and grinding the
teeth. It most often occurs at night during sleep, but it
may also occur during the day. It is an unconscious
behavior, perhaps performed to release anxiety,
aggression, or anger.

Description
Bruxism is one of the oldest disorders known, and
approximately one in four adults experiences it. Most
people are not aware of it before their teeth have been
damaged.

Causes and symptoms
While bruxism is typically associated with stress, it
may also be triggered by abnormal occlusion (the way
the upper and lower teeth fit together), or crooked or
missing teeth.
Symptoms of bruxism include: dull headaches;
sore and tired facial muscles; earaches; sensitive
teeth; and locking, popping, and clicking of the jaw.
During a dental examination, a dentist may recognize damage resulting from bruxism, including:
enamel loss from the chewing surfaces of teeth; flattened tooth surfaces; loosened teeth; and fractured
teeth and fillings. Left untreated, bruxism may lead
to tooth loss and jaw dysfunction.
676

Diagnosis
Medical and dental histories and examinations
are necessary to differentiate bruxism from other conditions that may cause similar pain, such as ear infections, dental infections, and temporomandibular joint
(TMJ) dysfunction. However, uncommonly worndown teeth strongly suggest a diagnosis of bruxism.

Treatment
To prevent further damage to the teeth, bruxism is
treated by placing a removable, custom-fitted plastic
appliance called a night guard between the upper and
lower teeth. Although the clenching and grinding
behavior may continue, the teeth wear away the plastic
instead of each other.
In some cases, abnormal occlusion may be adjusted
and high spots removed so that the teeth fit together in
a more comfortable position. Missing teeth may be
replaced and crooked teeth may be straightened with
orthodontic treatment to eliminate possible underlying
causes of bruxism. In cases where jaw muscles are very
tight, a dentist may prescribe muscle relaxants.

Alternative treatment
Stress management and behavior modification
techniques may be useful to break the habit of
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Ascites—Accumulation of fluid in the abdomen.
Biopsy—Surgical removal of a tiny bit of tissue for
examination under the microscope.
Catheter—A tubular surgical instrument.
Phlebitis—Inflammation of a vein.

Prognosis

Polycythemia vera—An excess number of red
blood cells in the blood.
Sickle cell anemia—An inherited disease in which
red blood cells take an unusual shape, leading to
circulation problems.

Bruxism may cause permanent damage to teeth
and chronic jaw pain unless properly diagnosed and
promptly treated. The behavior may be eliminated if
its underlying causes are found and addressed.

Prevention
Increased awareness in patients prone to anxiety,
aggression, or anger may prevent the habit of bruxism
from developing.

leading to blood clots within the liver. Also, some
of the blood plasma can leak through the walls of the
veins and accumulate within the abdomen (ascites).

Resources

Causes and symptoms

ORGANIZATIONS

Academy of General Dentistry. Suite 1200, 211 East
Chicago Ave., Chicago, IL 60611.(312) 440-4300.
<http://www.agd.org>.
American Dental Association. 211 E. Chicago Ave., Chicago,
IL 60611. (312) 440-2500. <http://www.ada.org>.

Bethany Thivierge

The major symptoms include pain in the upper
right-hand portion of the abdomen and a build-up of
fluid in the abdomen. In the United States, blood
disorders are the most common causes. Among these
disorders are polycythemia vera (an increase in the
number of red blood cells), and sickle cell anemia. In
parts of the world where liver cancer is common, a
form of liver cancer is the most frequent cause.

Bubonic plague see Plague

I Budd-Chiari syndrome
Definition
Budd-Chiari syndrome is a rare problem that
results from blood clotting in the veins flowing out of
the liver (hepatic veins). The high pressure of blood in
these veins leads to an enlarged liver, and to an accumulation of fluid in the abdomen, called ascites.

Description
The liver, the largest internal organ in the human
body, is responsible for many vital physiologic processes. Blood flow through the liver nourishes the
liver, carries in substances that the liver will process,
and carries away substances that the liver has produced. When blood cannot flow out freely from the
liver, blood pressure rises in the veins of the liver,
GALE ENCYCLOPEDIA OF MEDICINE

Other causes sometimes include:


certain infections



use of oral contraceptives



body changes in pregnancy and the postpartum period



phlebitis (inflammation of a vein)



injury to the abdomen



membranous webs (especially in Asia)

Diagnosis
Diagnosis of Budd-Chiari syndrome can be made
by an internist (a specialist in diseases of the internal
organs), a gastroenterologist (a specialist in the diseases of the digestive system), or a general surgeon. On
physical examination, the doctor will note that the liver
is larger than normal. Often an ultrasound scan of the
liver will show abnormalities in the size of the liver, an
abnormal pattern of the veins in the liver, and other
abnormalities. A CT scan will often show similar
abnormalities.
677

Budd-Chiari syndrome

clenching and teeth grinding. Tight jaw muscles may
be relaxed by applying warm compresses to the sides
of the face. Herbal muscle relaxants also can be helpful. Massage therapy and deep tissue realignment,
including rolfing, can assist in releasing the clenching
pattern. This is a more permanent alternative treatment for bruxism.

Buerger’s disease

Once these abnormalities are confirmed, the key
test is called hepatic vein catheterization. In this test, a
narrow tube is snaked through the body until it
reaches the hepatic veins. An instrument at the tip of
the catheter can measure the pressure within each
segment of the hepatic vein.
In some cases, a tiny amount of radioactive material is injected into a patient, and then an abnormal
pattern of radioactivity in the liver can be revealed.
In other cases, a liver biopsy enables a physician to
examine cells from the liver itself. Cells damaged by
Budd-Chiari syndrome have a characteristic appearance easily identifiable to a physician.

Treatment
Surgery
Most patients with Budd-Chiari syndrome must
have surgery. A surgeon will re-route blood flow
around the clotted hepatic vein into a large vein called
the vena cava. The exact technique will depend on the
specific location of the clots and other factors. In certain
patients, other surgical techniques may be used. For
patients who otherwise would have less than six months
to live, liver transplantation is sometimes performed.
In a few patients, a ‘‘balloon catheter’’ can open
the blocked blood vessels, without the need for major
surgery.
Drugs
Sometimes, anti-clotting drugs such as urokinase
can be used for patients with a sudden onset of clotting
in the veins of the liver. These drugs do not seem to
work when the clots have become established.

Prognosis
If surgery is done before permanent liver damage
sets in, long-term survival is possible. In these cases,
damaged liver cells can actually recover. If patients are
already very sick with liver disease, the surgery may
not be as helpful.

Prevention
The best approach to prevention is to carefully
control the blood disorders that can lead to BuddChiari syndrome.
Resources
BOOKS

Gadacz, Thomas R., and John L. Cameron. ‘‘Budd-Chiari
Syndrome and Surgery of the Hepatic Vasculature.’’ In
678

Shackelford’s Surgery of the Alimentary Tract, edited by
J.G. Turcotte, 3rd ed. Vol. 3. Philadelphia: W. B.
Saunders Co., 1991.

Richard H. Lampert

I Buerger’s disease
Definition
Buerger’s disease is an inflammation of the arteries,
veins, and nerves in the legs, principally, leading to
restricted blood flow. Left untreated, Buerger’s disease
can lead to gangrene of the affected areas. Buerger’s
disease is also known as thromboangitis obliterans.

Causes and symptoms
The exact cause of Buerger’s disease is not known.
It is seen most often in young to middle-aged men
(ages 20-40) who are heavy smokers of cigarettes.
Cases of this disease in non-smokers are very rare,
hence, cigarette smoking is considered a causative factor. Approximately 40% of the patients have a history
of inflammation of a vein (phlebitis), which may play a
role in the development of Buerger’s disease. The disease is mainly seen in the legs of affected persons, but
may also appear in their arms. Early symptoms
include decrease in the blood supply (arterial ischemia)
and superficial (near the skin surface) phlebitis. The
main symptom is pain in the affected areas. Onset of
the disease is gradual and first occurs in the feet or
hands. Inflammation occurs in small and mediumsized arteries and veins near the surface of the limb.
In advanced cases, blood vessels in other parts of the
body may be affected. There is a progressive decrease
in the blood flow to the affected areas. The pulse in
arteries of the feet is weak or undetectable. The lack of
blood flow can lead to gangrene, which is decay of
tissue due to restricted blood supply. A cold sensitivity
in the hands, similar to that seen in Raynaud’s disease,
can develop. In this case, the hands turn color–white,
blue, and then red–when exposed to the cold.

Diagnosis
Diagnosis is usually made from the clinical symptoms. Patients frequently complain of numbness, tingling, or burning sensations in the affected area before
evidence of vascular inflammation becomes apparent.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Gangrene—A decay of the tissue in a part of the
body that experiences restricted blood flow.
Inflammation—A local reaction to irritation,
injury, or infection characterized by pain, swelling,
redness, and occasional loss of function.

Binge—To consume large amounts of food uncontrollably within a short time period.
Diuretic—A drug that promotes the formation and
excretion of urine.

Ischemia—A decrease in the blood supply to an
area of the body caused by obstruction or constriction of blood vessels.
Phlebitis—Inflammation of a vein.

Treatment
There is no effective medication or surgery for this
disease. Patients must stop smoking to halt further
development of the symptoms. Vasodilators, drugs
that increase the diameter of the blood vessels, can
be administered, but may not be effective. Exposure
of affected areas to heat or cold should be avoided.
Trauma to the feet and other affected areas should be
avoided and infections must be treated promptly.

Prognosis
The disease is progressive in patients who do not
stop smoking. Areas with gangrene must be removed
surgically.

Neurotransmitters—Certain brain chemicals that
may function abnormally in acutely ill bulimic
patients.
Obsessive-compulsive disorder (OCD)—A disorder that may accompany bulimia, characterized
by the tendency to perform repetitive acts or rituals
in order to relieve anxiety.
Purge—To rid the body of food and calories, commonly by vomiting or using laxatives.

women. People with bulimia, known as bulimics,
consume large amounts of food (binge) and then try
to rid themselves of the food and calories (purge) by
fasting, excessive exercise, vomiting, or using laxatives.
The behavior often serves to reduce stress and relieve
anxiety. Because bulimia results from an excessive
concern with weight control and self-image, and is
often accompanied by depression, it is also considered
a psychiatric illness.

Description
Prevention
Smoking is the only known causative agent for
this disease and should be avoided.
Resources
BOOKS

Berkow, R., editor. The Merck Manual. 17th ed. Rahway,
NJ: Merck and Co., 1997.

John T. Lohr, PhD

Bulging eyes see Exophthalmos

I Bulimia nervosa
Definition
Bulimia nervosa is a serious and sometimes lifethreatening eating disorder affecting mainly young
GALE ENCYCLOPEDIA OF MEDICINE

Bulimia nervosa is a serious health problem for
over two million adolescent girls and young women in
the United States. The bingeing and purging activity
associated with this disorder can cause severe damage,
even death, although the risk of death is not as high as
for anorexia nervosa, an eating disorder that leads to
excessive weight loss.
Binge eating may in rare instances cause the stomach to rupture. In the case of purging, heart failure
can result due to loss of vital minerals such as potassium. Vomiting causes other serious problems, including acid-related scarring of the fingers (if used to induce
vomiting) and damage to tooth enamel. In addition, the
tube that brings food from the mouth to the stomach
(the esophagus) often becomes inflamed and salivary
glands can become swollen. Irregular menstrual periods
can also result, and interest in sex may diminish.
Most bulimics find it difficult to stop their behavior
without professional help. Many typically recognize
that the behavior is not normal, but feel out of control.
Some bulimics struggle with other compulsive, risky
679

Bulimia nervosa

KEY TERMS

Bulimia nervosa
The cuts on the knuckles shown in this photograph are due to the teeth breaking the skin during self-induced vomiting.
(B. Bodine/Custom Medical Stock Photo, Inc. Reproduced by permission.)

behaviors such as drug and alcohol abuse. Many also
suffer from other psychiatric illnesses, including clinical depression, anxiety, and obsessive-compulsive disorder (OCD).
Most bulimics are females in their teens or early
20s. Males account for only 5-10% of all cases. People
of all races develop the disorder, but most of those
diagnosed are white.
Bulimic behavior is often carried out in secrecy,
accompanied by feelings of guilt or shame. Outwardly,
many people with bulimia appear healthy and successful, while inside they have feelings of helplessness and
low self-esteem.

Symptoms

Causes and symptoms

According to the American Anorexia/Bulimia
Association, Inc., warning signs of bulimia include:

Causes



eating large amounts of food uncontrollably (bingeing)



vomiting, abusing laxatives or diuretics, or engaging
in fasting, dieting, or vigorous exercise (purging)



preoccupation with body weight



using the bathroom frequently after meals

The cause of bulimia is unknown. Researchers
believe that it may be caused by a combination of
genetic and environmental factors. Bulimia tends to
run in families. Research shows that certain brain
chemicals, known as neurotransmitters, may function
680

abnormally in acutely ill bulimia patients. Scientists
also believe there may be a link between bulimia and
other psychiatric problems, such as depression and
OCD. Environmental influences include participation in work or sports that emphasize thinness, such
as modeling, dancing, or gymnastics. Family pressures also may play a role. One study found that
mothers who are extremely concerned about their
daughters’ physical attractiveness and weight may
help to cause bulimia. In addition, girls with eating
disorders tend to have fathers and brothers who criticize their weight.

GALE ENCYCLOPEDIA OF MEDICINE

depression or mood swings



irregular menstrual periods



onset of dental problems, swollen cheeks or glands,
heartburn or bloating

Diagnosis
Bulimia is treated most successfully when diagnosed early. But because the bulimic may deny there
is a problem, getting medical help is often delayed. A
complete physical examination in order to rule out
other illnesses is the first step to diagnosis.
According to the American Psychiatric Association, a diagnosis of bulimia requires that a person
have all of the following symptoms:

eating disorder clinics in local hospitals or treatment
programs in colleges designed for students.

Alternative treatment
Light therapy–exposure to bright, artificial light–
may be useful in reducing bulimic episodes, especially
during the dark winter months. Some feel that massage may prove helpful, putting people in touch with
the reality of their own bodies and correcting misconceptions of body image. Hypnotherapy may help
resolve unconscious issues that contribute to bulimic
behavior.

Prognosis



recurrent episodes of binge eating (minimum average
of two binge-eating episodes a week for at least three
months)

Bulimia may become chronic and lead to serious
health problems, including seizures, irregular heartbeat, and thin bones. In rare cases, it may be fatal.



a feeling of lack of control over eating during the
binges



regular use of one or more of the following to prevent
weight gain: self-induced vomiting, use of laxatives
or diuretics, strict dieting or fasting, or vigorous
exercise

Timely therapy and medication can effectively
manage the disorder and help the bulimic look forward to a normal, productive, and fulfilling life.



persistent over-concern with body shape and weight

Prevention
There is no known method to prevent bulimia.
Resources

Treatment
Early treatment is important otherwise bulimia
may become chronic, with serious health consequences. A comprehensive treatment plan is called
for in order to address the complex interaction of
physical and psychological problems in bulimia. A
combination of drug and behavioral therapies is commonly used.
Behavioral approaches include individual psychotherapy, group therapy, and family therapy.
Cognitive-behavioral therapy, which teaches patients
how to change abnormal thoughts and behavior, is
also used. Nutrition counseling and self-help groups
are often helpful.
Antidepressants commonly used to treat bulimia
include desipramine (Norpramin), imipramine
(Tofranil), and fluoxetine (Prozac). These medications
also may treat any co-existing depression.
In addition to professional treatment, family support plays an important role in helping the bulimic
person. Encouragement and caring can provide the
support needed to convince the sick person to get
help, stay with treatment, or try again after a failure.
Family members can help locate resources, such as
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Anorexia/Bulimia Association, Inc. 293 Central
Park West, Suite IR, New York, NY 10024. (212)
501-8351.
Anorexia Nervosa and Related Eating Disorders, Inc. P.O.
Box 5102, Eugene, OR 97405. (541) 344-1144.
Center for the Study of Anorexia and Bulimia. 1 W. 91st St.,
New York, NY 10024. (212) 595-3449.
Eating Disorder Awareness. & Prevention, Inc., 603
Stewart St., Suite 803, Seattle, WA 98101. (206)
382-3587.
National Association of Anorexia Nervosa and Associated
Disorders. Box 7, Highland Park, IL 60035. (708)
831-3438.
National Eating Disorders Organization (NEDO).
6655 South Yale Ave, Tulsa, OK 74136. (918)
481-4044.

Jennifer Lamb

Bulla see Skin lesions
Bumetanide see Diuretics
BUN see Blood urea nitrogen test
681

Bulimia nervosa



Bunion

I Bundle branch block
Definition
Bundle branch block (BBB) is a disruption in the
normal flow of electrical pulses that drive the heart
beat.

Description
Bundle branch block belongs to a group of heart
problems called intraventricular conduction defects
(IVCD). There are two bundle branches, right and
left. The right bundle carries nerve impulses that
cause contraction of the right ventricle (the lower
chamber of the heart) and the left bundle carries
nerve impulses that cause contraction of the left ventricle. The two bundles initially are together at a junction called the bundle of His. Nerve impulses come
through the sinus node of the heart to the bundle of
His and then move into the right and left bundle
branches. Bundle branch block is a slowing or interruption of nerve impulses. A problem may exist in any
of the three bundles.
Patients with BBB are generally without symptoms unless the disease is severe enough to cause a
complete infranodal A-V block and very slow heart
rate. In patients with right bundle branch block
(RBBB), the nerve impulse is conducted slowly or not
at all. The right ventricle finally receives the impulse
through muscle-to-muscle spread, outside the regular
nerve pathway. This mechanism of impulse transmission is slow and results in a delayed contraction of the
right ventricle. There are several types of left bundle
branch block (LBBB), each producing its own characteristic mechanism of failure. In each case, the nerve
impulse is blocked or delayed. Patients with LBBB
may have left ventricular disease or cardiomyopathy.

Causes and symptoms
Left bundle branch block usually happens as a
consequence of other diseases such as arteriosclerosis,
rheumatic fever, congenital heart disease, myocarditis,
myocardial infarction, metastatic heart tumors, or
other invasions of the heart tissue. Right bundle branch
block happens less often from underlying heart disease.

Diagnosis
Detection of BBB usually takes place during a
normal physical examination. The block shows up as
a widening of the second heart sound. Confirmation
682

KEY TERMS
Electrocardiogram—The pattern of the heart’s
electrical impulses that indicate the order and condition of the heart’s components.
QRS—A pattern seen in an electrocardiogram that
indicates the pulses in a heart beat and their duration. Variations from a normal QRS pattern indicate
heart disease.

of BBB is obtained by electrocardiogram (ECG).
The pattern seen in the electrocardiogram indicates
pulses in a heart beat and their duration. A QRS
duration of greater than 110 milliseconds is a diagnostic indication of BBB. There is a unique ECG pattern
for blocks in each of the three bundles.

Treatment
There is no specific therapy for BBB. Patients are
usually treated for associated heart diseases.

Prognosis
The prognosis of blockage in any of the three
bundle branches depends on the prognosis of the associated heart disease. The associated diseases determine
the outcome of the patient’s health. Occasionally,
disruptions in bundle branches lead to complete infranodal A-V block, a more serious blockage of nerve
impulses. Approximately 2% of patients with BBB
develop infranodal A-V blockage and these patients
often require artificial pacemakers.
Resources
BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, editors. The
Heart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD

I Bunion
Definition
A bunion is an abnormal enlargement of the joint
(the first metatarsophalangeal joint, or MTPJ) at the
base of the great or big toe (hallux). It is caused
GALE ENCYCLOPEDIA OF MEDICINE

Bunion

KEY TERMS
Orthopedics—A medical specialty concerned with
treating diseases, injuries, and malformations of the
bones and supporting structures, such as tendons,
ligaments, and muscles.
Orthotic—A device or brace to control, correct, or
compensate for a bone deformity.
Podiatry—A medical specialty concerned with treating diseases, injuries, and malformations of the feet.

Woman’s right foot with bunion on big toe. (Photograph by
Wedgworth, Custom Medical Stock Photo. Reproduced by
permission.)

by inflammation and usually results from chronic irritation and pressure from poorly fitting footwear.

Description
A displacement of two major bones of the foot
(hallux valgus) causes bunions, although not everyone
with this displacement will develop the joint swelling
and bone overgrowth that characterize a bunion. One
of the bones involved is called the first metatarsal
bone. This bone is long and slender, with the big toe
attached on one end and the other end connected to
foot bones closer to the ankle. This foot bone is displaced in the direction of the four other metatarsals
connected with the toes. The other bone involved is the
big toe itself, which is displaced toward the smaller
toes. As the big toe continues to move toward the
smaller toes, it may become displaced under or over
the second toe. The displacement of these two foot
bones causes a projection of bone on the inside portion
of the forefoot. The skin over this projection often
becomes inflamed from rubbing against the shoe,
and a callus may form.
The joint contains a small sac (bursa) filled with
fluid that cushions the bones and helps the joint to
move smoothly. When a bunion forms, this sac
becomes inflamed and thickened. The swelling in the
joint causes additional pain and pressure in the toe.

Causes and symptoms
Bunions may form as a result of abnormal motion
of the foot during walking or running. One common
example of an abnormal movement is an excessive
amount of stress placed upon the inside of the foot.
This leads to friction and irritation of the involved
GALE ENCYCLOPEDIA OF MEDICINE

structures. Age has also been noted as a factor in
developing bunions, in part because the underlying
bone displacement worsens over time unless corrective
measures are taken.
Wearing improperly fitting shoes, especially those
with a narrow toe box and excessive heel height, often
causes the formation of a bunion. This forefoot deformity is seen more often in women than men. The
higher frequency in females may be related to the
strong link between footwear fashion and bunions.
In fact, in a recent survey of more than 350 women,
nearly 90% wore shoes that were at least one size too
small or too narrow.
Because genetic factors can predispose people to
the hallux valgus bone displacement, a strong family
history of bunions can increase the likelihood of developing this foot disorder. Various arthritic conditions
and several genetic and neuromuscular diseases, such
as Down syndrome and Marfan syndrome, cause
muscle imbalances that can create bunions from
displacement of the first metatarsal and big toe.
Other possible causes of bunions are leg-length discrepancies, with the bunion present on the longer leg, and
trauma occurring to the joint of the big toe.
Symptoms of bunions include the common signs
of inflammation such as redness, swelling, and pain.
The discomfort is primarily located along the inside of
the foot just behind the big toe. Because of friction, a
callus may develop over the bunion. If an overlapping
of the toes is allowed, additional rubbing and pain
occurs. Inflammation of this area causes a decrease
in motion with associated discomfort in the joint
between the big toe and the first metatarsal. If allowed
to worsen, the skin over the bunion may break down
causing an ulcer, which also presents a problem of
potential infection. (Foot ulcers can be particularly
dangerous for people with diabetes, who may have
trouble feeling the ulcer forming and healing if it
becomes infected.)
683

Bunion

Diagnosis
A thorough medical history and physical exam
by a physician is always necessary for the proper diagnosis of bunions and other foot conditions. X rays
can help confirm the diagnosis by showing the bone
displacement, joint swelling, and, in some cases, the
overgrowth of bone that characterizes bunions.
Doctors will also consider the possibility that the
joint pain is caused by or complicated by arthritis
(which causes destruction of the cartilage of the
joint), gout (which causes the accumulation of uric
acid crystals in the joint), tiny fractures of a bone in
the foot (stress fractures), or infection and may order
additional tests to rule out these possibilities.

Treatment
Conservative
The first step in treating a bunion is to remove
as much pressure from the area as possible. People
with bunions should wear shoes that have enough
room in the toe box to accommodate the bunion
and avoid high-heeled shoes and tight-fitting socks
or stockings. Dressings and pads help protect the
bunion from additional shoe pressure. The application of splints or customized shoe inserts (orthotics)
to correct the alignment of the big toe joint is effective
for many bunions. Most patients are instructed to
rest or choose exercises that put less stress on their
feet, at least until the misalignment is corrected.
In some cases, physicians also use steroid injections
with local anesthetic around the bunion to reduce
inflammation.
Surgery
If conservative treatment is not successful, surgical removal of the bunion may be necessary to correct
the deformity. This procedure is called a bunionectomy, and there are many variations on the operation,
which is usually performed by a surgeon who specializes in treating bone conditions (orthopedics) or by
one who specializes in treating the foot (podiatry).
Surgeons consider the angle of the bone misalignment,
the condition of the bursa, and the strength of the
bones when they choose which procedure to use.
Most bunionectomies involve the removal of a section
of bone and the insertion of pins to rejoin the bone.
Sometimes the surgeons may move ligaments (which
connect bone to bone in the joint) or tendons (which
connect bone to muscle) in order to realign the bones.
After this procedure, the bones and other tissues are
held in place while they heal by compression dressings
684

or a short cast. The individual must refrain from vigorous exercise for six weeks.

Alternative treatment
Deep friction massage techniques by a physical or
massage therapist can be helpful to increase circulation, reduce inflammation, and prevent soft tissue
build up. Physical therapy also provides useful
approaches such as ultrasound to help retard or
reverse the formation of the bunion. Various taping
techniques can be useful to realign the toe and decrease
friction and rubbing that may be present. The homeopathic tissue salt Calcarea phosphorica can be useful
in balancing the bone formation/remodeling.

Prognosis
Often modifications in footwear allow a good
prognosis without surgery. If surgery is necessary,
complete healing without complications requires
approximately four to six weeks. Even after surgery
corrects the bone misalignment, patients are usually
instructed to continue wearing low-heeled, roomy
shoes to prevent the bunion from reforming.

Prevention
Prevention begins with proper foot wear. Shoes
with a wide and deep toe box are best. High-heeled
shoes should not be worn for long periods of time. If a
bunion is present and becomes inflamed, the foot
should be elevated with the application of an ice
pack over the painful area for not more than 20
minutes every other hour. If pain and swelling continue, a podiatrist or physician should be contacted.
Resources
ORGANIZATIONS

American Orthopedic Foot and Ankle Society. 222 South
Prospect, Park Ridge, IL 60068.
American Podiatry Medical Association. 9312 Old
Georgetown Road, Bethesda, MD 20814.
OTHER

Griffith, H. Winter. ‘‘Complete Guide to Symptoms, Illness
& Surgery.’’ ThriveOnline. <http://
thriveonline.oxygen.com>.

Jeffrey P. Larson, RPT

Burkitt’s lymphoma see Malignant
lymphomas
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Burns are injuries to tissues caused by heat, friction, electricity, radiation, or chemicals.

Description
Burns are characterized by degree, based on the
severity of the tissue damage. A first-degree burn
causes redness and swelling in the outermost layers
of skin (epidermis). A second-degree burn involves
redness, swelling and blistering, and the damage may
extend beneath the epidermis to deeper layers of skin
(dermis). A third-degree burn, also called a full-thickness burn, destroys the entire depth of skin, causing
significant scarring. Damage also may extend to the
underlying fat, muscle, or bone.
The severity of the burn is also judged by the
amount of body surface area (BSA) involved. Health
care workers use the ‘‘rule of nines’’ to determine the
percentage of BSA affected in patients more than
9 years old: each arm with its hand is 9% of BSA;
each leg with its foot is 18%; the front of the torso is
18%; the back of the torso, including the buttocks, is
18%; the head and neck are 9%; and the genital area
(perineum) is 1%. This rule cannot be applied to a
young child’s body proportions, so BSA is estimated
using the palm of the patient’s hand as a measure of
1% area.
The severity of the burn will determine not only
the type of treatment, but also where the burn patient
should receive treatment. Minor burns may be treated
at home or in a doctor’s office. These are defined as
first- or second-degree burns covering less than 15%
of an adult’s body or less than 10% of a child’s body,
or a third-degree burn on less than 2% BSA. Moderate
burns should be treated at a hospital. These are
defined as first- or second-degree burns covering
15%-25% of an adult’s body or 10%-20% of a child’s
body, or a third-degree burn on 2%-10% BSA.
Critical, or major, burns are the most serious and
should be treated in a specialized burn unit of a hospital. These are defined as first- or second-degree burns
covering more than 25% of an adult’s body or more
than 20% of a child’s body, or a third-degree burn on
more than 10% BSA. In addition, burns involving
the hands, feet, face, eyes, ears, or genitals are considered critical. Other factors influence the level of treatment needed, including associated injuries such as
bone fractures and smoke inhalation, presence of a
chronic disease, or a history of being abused. Also,
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Burns may be caused by even a brief encounter
with heat greater than 120  F (49  C). The source of
this heat may be the sun (causing a sunburn), hot
liquids, steam, fire, electricity, friction (causing rug
burns and rope burns), and chemicals (causing a caustic burn upon contact).
Signs of a burn are localized redness, swelling, and
pain. A severe burn will also blister. The skin may also
peel, appear white or charred, and feel numb. A burn
may trigger a headache and fever. Extensive burns
may induce shock, the symptoms of which are faintness, weakness, rapid pulse and breathing, pale and
clammy skin, and bluish lips and fingernails.

Diagnosis
A physician will diagnose a burn based upon visual
examination, and will also ask the patient or family
members questions to determine the best treatment. He
or she may also check for smoke inhalation, carbon monoxide poisoning, cyanide poisoning, other event-related
trauma, or, if suspected, further evidence of child abuse.

Treatment
Burn treatment consists of relieving pain, preventing infection, and maintaining body fluids, electrolytes, and calorie intake while the body heals.
Treatment of chemical or electrical burns is slightly
different from the treatment of thermal burns but the
objectives are the same.
Thermal burn treatment
The first act of thermal burn treatment is to stop
the burning process. This may be accomplished by
letting cool water run over the burned area or by
soaking it in cool (not cold) water. Ice should never
be applied to the burn. Cool (not cold) wet compresses
may provide some pain relief when applied to small
areas of first- and second-degree burns. Butter, shortening, or similar salve should never be applied to the
burn since it prevents heat from escaping and drives
the burning process deeper into the skin.
If the burn is minor, it may be cleaned gently with
soap and water. Blisters should not be broken. If the
skin of the burned area is unbroken and it is not likely to
be further irritated by pressure or friction, the burn
685

Burns

I Burns

children and the elderly are more vulnerable to complications from burn injuries and require more intensive care.

Burns

Epidermis

}

First-degree burn

Dermis
Second-degree burn

Subcutaneous
tissue
Third-degree burn

Blood vessels
Nerve

Hair follicle

There are three classifications of burns: first-degree, second-degree, and third-degree burns. (Illustration by Electronic Illustrators
Group.)

Classification Of Burns

First-Degree
(Minor)
Second-Degree
(Moderate)
Third-Degree
(Critical)

The burned area is painful. The outer skin is
reddened. Slight swelling is present.
The burned area is painful. The underskin is affected.
Blisters may form. The area may have a wet, shiny
appearance because of exposed tissue.
The burned area is insensitive due to the destruction
of nerve endings. Skin is destroyed. Muscle tissues
and bone underneath may be damaged. The area
may be charred, white, or grayish in color.

should be left exposed to the air to promote healing. If
the skin is broken or apt to be disturbed, the burned area
should be coated lightly with an antibacterial ointment
and covered with a sterile bandage. Aspirin, acetaminophen (Tylenol), or ibuprofen (Advil) may be taken to
ease pain and relieve inflammation. A doctor should be
consulted if these signs of infection appear: increased
warmth, redness, pain, or swelling; pus or similar
drainage from the wound; swollen lymph nodes; or
red streaks spreading away from the burn.
686

In situations where a person has received moderate or critical burns, lifesaving measures take precedence over burn treatment and emergency medical
assistance must be called. A person with serious
burns may stop breathing, and artificial respiration
(also called mouth-to-mouth resuscitation or rescue
breathing) should be administered immediately.
Also, a person with burns covering more than 12%
BSA is likely to go into shock; this condition may be
prevented by laying the person flat and elevating
the feet about 12 in (30 cm). Burned arms and
hands should also be raised higher than the person’s
heart.
In rescues, a blanket may be used to smother any
flames as the person is removed from danger. The
person whose clothing is on fire should ‘‘stop, drop,
and roll’’ or be assisted in lying flat on the ground and
rolling to put out the fire. Afterwards, only burnt clothing that comes off easily should be removed; any clothing embedded in the burn should not be disturbed.
Removing any smoldering apparel and covering the
person with a light, cool, wet cloth, such as a sheet but
not a blanket or towel, will stop the burning process.
GALE ENCYCLOPEDIA OF MEDICINE

Debridement—The surgical removal of dead tissue.
Dermis—The basal layer of skin; it contains blood
and lymphatic vessels, nerves, glands, and hair
follicles.
Epidermis—The outer portion of skin, made up of
four or five superficial layers.
Shock—An abnormal condition resulting from low
blood volume due to hemorrhage or dehydration.
Signs of shock include rapid pulse and breathing,
and cool, moist, pale skin.

At the hospital, the staff will provide further
medical treatment. A tube to aid breathing may be
inserted if the patient’s airways or lungs have been
damaged, as can happen during an explosion or a fire
in a enclosed space. Also, because burns dramatically
deplete the body of fluids, replacement fluids are
administered intravenously. The patient is also
given antibiotics intravenously to prevent infection,
and he or she may also receive a tetanus shot, depending on his or her immunization history. Once the
burned area is cleaned and treated with antibiotic
cream or ointment, it is covered in sterile bandages,
which are changed two to three times a day. Surgical
removal of dead tissue (debridement) also takes place.
As the burns heal, thick, taut scabs (eschar) form,
which the doctor may have to cut to improve blood
flow to the more elastic healthy tissue beneath. The
patient will also undergo physical and occupational
therapy to keep the burned areas from becoming
inflexible and to minimize scarring.
In cases where the skin has been so damaged that
it cannot properly heal, a skin graft is usually performed. A skin graft involves taking a piece of skin
from an unburned portion of the patient’s body
(autograft) and transplanting it to the burned area.
When doctors cannot immediately use the patient’s
own skin, a temporary graft is performed using the
skin of a human donor (allograft), either alive or
dead, or the skin of an animal (xenograft), usually
that of a pig.
The burn victim also may be placed in a hyperbaric chamber, if one is available. In a hyperbaric chamber (which can be a specialized room or enclosed
space), the patient is exposed to pure oxygen under
high pressure, which can aid in healing. However, for
GALE ENCYCLOPEDIA OF MEDICINE

this therapy to be effective, the patient must be placed
in a chamber within 24 hours of being burned.
Chemical burn treatment
Burns from liquid chemicals must be rinsed with
cool water for at least 15 minutes to stop the burning
process. Any burn to the eye must be similarly flushed
with water. In cases of burns from dry chemicals such
as lime, the powder should be completely brushed
away before the area is washed. Any clothing which
may have absorbed the chemical should be removed.
The burn should then be loosely covered with a sterile
gauze pad and the person taken to the hospital for
further treatment. A physician may be able to neutralize the offending chemical with another before
treating the burn like a thermal burn of similar
severity.
Electrical burn treatment
Before electrical burns are treated at the site of the
accident, the power source must be disconnected if
possible and the victim moved away from it to keep
the person giving aid from being electrocuted.
Lifesaving measures again take priority over burn
treatment, so breathing must be checked and assisted
if necessary. Electrical burns should be loosely covered
with sterile gauze pads and the person taken to the
hospital for further treatment.

Alternative treatment
In addition to the excellent treatment of burns
provided by traditional medicine, some alternative
approaches may be helpful as well. (Major burns should
always be treated by a medical practitioner.) The
homeopathic remedies Cantharis and Causticum can
assist in burn healing. A number of botanical remedies,
applied topically, can also help burns heal. These
include aloe (Aloe barbadensis), oil of St.-John’s-wort
(Hypericum perforatum), calendula (Calendula officinalis), comfrey (Symphytum officinale), and tea tree oil
(Melaleuca spp.). Supplementing the diet with vitamin
C, vitamin E, and zinc also is beneficial for wound
healing.

Prognosis
The prognosis is dependent upon the degree of the
burn, the amount of body surface covered, whether
critical body parts were affected, any additional injuries or complications like infection, and the promptness of medical treatment. Minor burns may heal in
five to 10 days with no scarring. Moderate burns may
687

Burns

KEY TERMS

Bursitis

heal in 10-14 days and may leave scarring. Critical
or major burns take more than 14 days to heal and
will leave significant scarring. Scar tissue may limit
mobility and functionality, but physical therapy may
overcome these limitations. In some cases, additional
surgery may be advisable to remove scar tissue and
restore appearance.

Prevention
Burns are commonly received in residential fires.
Properly placed and working smoke detectors in combination with rapid evacuation plans will minimize a person’s exposure to smoke and flames in the event of a fire.
Children must be taught never to play with matches,
lighters, fireworks, gasoline, and cleaning fluids.
Burns by scalding with hot water or other liquids
may be prevented by setting the water heater thermostat no higher than 120  F (49  C), checking the temperature of bath water before getting into the tub, and
turning pot handles on the stove out of the reach of
children. Care should be used when removing covers
from pans of steaming foods and when uncovering or
opening foods heated in a microwave oven.
Thermal burns are often received from electrical
appliances. Care should be exercised around stoves,
space heaters, irons, and curling irons.
Sunburns may be avoided by the liberal use of a
sunscreen containing either an opaque active ingredient
such as zinc oxide or titanium dioxide or a nonopaque
active ingredient such as PABA (para-aminobenzoic
acid) or benzophenone. Hats, loose clothing, and
umbrellas also provide protection, especially between
10 A.M. and 3 P.M. when the most damaging ultraviolet rays are present in direct sunlight.
Electrical burns may be prevented by covering
unused electrical outlets with safety plugs and keeping
electrical cords away from infants and toddlers who
might chew on them. Persons should also seek shelter
indoors during a thunderstorm to avoid being struck
by lightning.
Chemical burns may be prevented by wearing
protective clothing, including gloves and eyeshields.
Chemical agents should always be used according to
the manufacturer’s instructions and properly stored
when not in use.
Resources
ORGANIZATIONS

Shriners Hospitals for Children. 2900 Rocky Point Drive,
Tampa, FL 33607-1435. (813) 281-0300. <http://
www.shrinershq.org>.
688

OTHER

HealthAnswers.com. <http://www.healthanswers.com>.

Bethany Thivierge

I Bursitis
Definition
Bursitis is the painful inflammation of the bursa,
a padlike sac found in areas subject to friction.
Bursae cushion the movement between the bones,
tendons and muscles near the joints. Bursitis is most
often caused by repetitive movement and is known by
several common names including weaver’s bottom,
clergyman’s knee, and miner’s elbow, depending on
the affected individual’s occupation and area of
injury.

Description
There are over 150 bursae in the human body.
Usually bursae are present from birth, but they may
form in response to repeated pressure. Each sac contains a small amount of synovial fluid, a clear liquid
that acts as a lubricant. Inflammation causes pain on
movement. The most common site for bursitis to occur
is the shoulder (subdeltoid), but it also is seen in the
elbows (olecranon), hips (trochanteric), knees, heels
(Achilles), and toes. The affected area may be referred
to as ‘‘frozen,’’ because movement is so limited. In the
knee there are four bursae, and all can become
inflamed with overuse.

Causes and symptoms
The most common cause of bursitis is repeated
physical activity, but it can flare up for no known
reason. It can also be caused by trauma, rheumatoid
arthritis, gout, and acute or chronic infection.
Pain and tenderness are common symptoms. If
the affected joint is close to the skin, as with the
shoulder, knee, elbow, or Achilles tendon, swelling
and redness are seen and the area may feel warm to
the touch. The bursae around the hip joint are deeper,
and swelling is not obvious. Movement may be limited
and is painful. In the shoulder, it may be difficult to
raise the arm out from the side of the body. Putting on
a jacket or combing the hair becomes a troublesome
activity.
GALE ENCYCLOPEDIA OF MEDICINE

Arthritis—Inflammation of a joint that may lead to
changes in the joint’s structure. It causes pain and
swelling. Rheumatoid arthritis is a chronic disease
that leads to crippling deformities.
Diabetes mellitus—A metabolic disease caused by
a deficiency of insulin, which is essential to process
carbohydrates in the body.
Gout—A hereditary metabolic disease that is a
form of arthritis and causes inflammation of the
joints. It is more common in men.
Inflammation—The reaction of tissue to injury.
Kinesiology—The science or study of movement.

In acute bursitis symptoms appear suddenly; with
chronic bursitis, pain, tenderness, and limited movement reappear after exercise or strain.

Diagnosis
When a patient has pain in a joint, a careful physical examination is needed to determine what type of
movement is affected and if there is any swelling present. Bursitis will not show up on x-rays, although
sometimes there are also calcium deposits in the joint
that can be seen. Inserting a thin needle into the
affected bursa and removing (aspirating) some of the
synovial fluid for examination can confirm the diagnosis. In most cases, the fluid will not be clear. It can
be tested for the presence of microorganisms, which
would indicate an infection, and crystals, which could
indicate gout. In instances where the diagnosis is difficult, a local anesthetic (a drug that numbs the area) is
injected into the painful spot. If the discomfort stops
temporarily, then bursitis is probably the correct
diagnosis.

Treatment
Conservative treatment of bursitis is usually effective. The application of heat, rest, and immobilization
of the affected joint area is the first step. A sling can be
used for a shoulder injury; a cane is helpful for hip
problems. The patient can take nonsteroidal antiinflammatory drugs (NSAIDs) like aspirin, ibuprofin,
and naproxen. They can be obtained without a prescription and relieve the pain and inflammation. Once
the pain decreases, exercises of the affected area can

GALE ENCYCLOPEDIA OF MEDICINE

begin. If the nearby muscles have become weak
because of the disease or prolonged immobility, then
exercises to build strength and improve movement are
best. A doctor or physical therapist can prescribe an
effective regimen.
If the bursitis is related to an inflammatory condition like arthritis or gout, then management of that
disease is needed to control the bursitis.
When bursitis does not respond to conservative
treatment, an injection into the joint of a long-acting
corticosteroid preparation, like prednisone, can
bring immediate and lasting relief. A corticosteroid
is a hormonal substance that is the most effective
drug for reducing inflammation. The drug is mixed
with a local anesthetic and works on the joint within
five minutes. Usually one injection is all that is
needed.
Surgery to remove the damaged bursa may be
performed in extreme cases.
If the bursitis is caused by an infection, then
additional treatment is needed. Septic bursitis is
caused by the presence of a pus-forming organism,
usually staphylococcus aureus. This is confirmed by
examining a sample of the fluid in the bursa and
requires treatment with antibiotics taken by mouth,
injected into a muscle or into a vein (intravenously).
The bursa will also need to be drained by needle
two or three times over the first week of treatment.
When a patient has such a serious infection, there
may be underlying causes. There could be undiscovered diabetes, or an inefficient immune system
caused by human immunodeficiency virus infection
(HIV).

Alternative treatment
Alternative treatments take into consideration
the role of diet in causing bursitis. The faulty use of
calcium by the body, magnesium deficiency, and
food allergies may have a role. Diet changes and
vitamin supplements may be helpful. The use of
herbs, homeopathy, aromatherapy, and hydrotherapy can help relieve symptoms. Ginger is useful in
reducing inflammation. Acupuncture has been proven effective in treating hip and shoulder pain caused
by bursitis and other conditions. Other therapies
that deal effectively with musculoskeletal problems
(relating to the muscles and skeleton), may also be
helpful, such as body work, magnetic field therapy,
naturopathic medicine, chiropractic, and applied
kinesiology.

689

Bursitis

KEY TERMS

Byssinosis

Prognosis
Bursitis usually responds well to treatment, but it
may develop into a chronic condition if the underlying
cause is not corrected.

Prevention
Aggravating factors should be eliminated to prevent bursitis. Overexercising or the repetition of a
movement that triggers the condition should be
avoided. Doing exercises to strengthen the muscles
around the joint will also help. When doing repetitive
tasks, frequent breaks should be taken and the
activity should be alternated with others using different parts of the body. To cushion the joints, it is a
good idea to use cushioned chairs when sitting and
foam kneeling pads for the knees. Leaning on the
elbows, kneeling or sitting on a hard surface for a
long period of time should be avoided. Not wearing
high heels can help prevent bursitis in the heel, as can
changing to new running shoes as soon as the old
ones are worn out.
Resources
OTHER

‘‘Bursitis.’’ HealthAnswers.com. 1998. <http://
www.healthanswers.com>.

Karen Ericson, RN

Bypass surgery see Coronary artery bypass
graft surgery

I Byssinosis
Definition
Byssinosis is a chronic, asthma-like narrowing of
the airways. Also called brown lung disease, byssinosis
results from inhaling particles of cotton, flax, hemp,
or jute.

Description
Although inhaling cotton dust was identified as a
source of respiratory disease more than 300 years
ago, byssinosis has been recognized as an occupational hazard for textile workers for less than 50
years. More than 800,000 workers in the cotton,
flax, and rope-making industries are exposed in the
workplace to airborne particles that can cause
690

KEY TERMS
Wheeze—A whistling sound made by the flow of
high-velocity air through narrowed airways.
Wheezing is a symptom of several respiratory diseases including byssinosis and asthma.

byssinosis. Only workers in mills that manufacture
yarn, thread, or fabric have a significant risk of dying
of this disease.
In the United States, byssinosis is almost completely limited to workers who handle unprocessed cotton. More than 35,000 textile workers have been
disabled by byssinosis and 183 died between 1979
and 1992. Most of the people whose deaths were due
to byssinosis lived in the textile-producing regions of
North and South Carolina.

Causes and symptoms
As many as 25% of workers with byssinosis have
symptoms that continue or recur throughout the
workweek. More severe breathing problems seem to
result both from exposure to high levels of dust and
from longer dust exposure. Workers who also smoke
cigarettes suffer the most severe impairment.

Diagnosis
Tests that detect decreasing lung capacity during
the workday are used to diagnose byssinosis.
Obstructive patterns are likely in patients who have
had recurrent symptoms for more than 10 years.

Treatment
Therapy for early-stage byssinosis focuses on
reversing airway narrowing. Antihistamines may be
prescribed to reduce tightness in the chest.
Bronchodilators (drugs used to relax breathing passages and improve air flow) may be used with an
inhaler or taken in tablet form. Reducing exposure is
essential. Any worker who has symptoms of byssinosis
or who has trouble breathing should transfer to a lesscontaminated area.

Prognosis
Smoking, impaired lung function, and a history of
respiratory allergy increase a textile worker’s risk of
developing byssinosis. Prolonged exposure makes
GALE ENCYCLOPEDIA OF MEDICINE

current United States standard for cotton dust
exposure.
Resources

Prevention
Eliminating exposure to textile dust is the surest
way to prevent byssinosis. Using exhaust hoods,
improving ventilation, and employing wetting procedures are very successful methods of controlling dust
levels to prevent byssinosis. Protective equipment
required during certain procedures also prevents
exposure to levels of contamination that exceed the

GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>

Maureen Haggerty

691

Byssinosis

patients wheeze more often and can cause chronic
bronchitis. It does not lead to permanently disabling
lung disease.

C
I C-reactive protein
Definition
C-reactive protein (CRP) is a protein produced by
the liver and found in the blood.

Purpose
C-reactive protein is not normally found in the
blood of healthy people. It appears after an injury,
infection, or inflammation and disappears when the
injury heals or the infection or inflammation goes
away. Research suggests that patients with prolonged
elevated levels of C-reactive protein are at an increased
risk for heart disease, stroke, hypertension (high blood
pressure), diabetes, and metabolic syndrome (insulin
resistance, a precursor of type 2 diabetes). The amount
of CRP produced by the body varies from person to
person, and this difference is affected by an individual’s genetic makeup (accounting for almost half of
the variation in CRP levels between different people)
and lifestyle. Higher CRP levels tend to be found in
individuals who smoke, have high blood pressure, are
overweight and do not exercise, whereas lean, athletic
individuals tend to have lower CRP levels.
The research shows that too much inflammation
can sometimes have adverse effects on the blood vessels
which transport oxygen and nutrients throughout the
body. Atherosclerosis, which involves the formation of
fatty deposits or plaques in the inner walls of the
arteries, is now considered in many ways an inflammatory disorder of the blood vessels, similar to the way
arthritis can be considered an inflammatory disorder of
the bones and joints. Inflammation affects the atherosclerotic phase of heart disease and can cause plaques to
rupture, which produces a clot and interfere with blood
flow, causing a heart attack or stroke.
There is an association between elevated levels of
inflammatory markers (including CRP) and the future
GALE ENCYCLOPEDIA OF MEDICINE

development of heart disease. This correlation applies
even to apparently healthy men and women who have
normal cholesterol levels. CRP level can be used by
physicians as part of the assessment of a patient’s risk
for heart disease because it is a stable molecule and can
be easily measured with a simple blood test. In patients
already suffering from heart disease, doctors can use
CRP levels to determine which patients are at high risk
for recurring coronary events.

Precautions
As of 2005, there are no precautions regarding the
C-reactive protein test. The person withdrawing blood
for the test should be notified if the patient is allergic to
latex or has a fear of needles.

Description
C-reactive protein was discovered in 1930, but few
people outside the medical community had heard of it
until stories about it began hitting the mainstream
media in early 2005. In 2005, two studies published
in the January 6, 2005, issue of The New England
Journal of Medicine provide the best evidence to date
that the C-reactive protein level in a person’s blood is
an important and highly accurate predictor of future
heart disease. C-reactive protein (CRP) is a sign of
inflammation in the walls of arteries. The studies
show that reducing the inflammation by lowering
CRP levels with a class of drugs known as statins
significantly lowers the rate of heart attacks and
coronary-artery disease in people with acute heart
disease. In fact, the studies indicated CRP levels may
be as important—if not more important—in predicting
and preventing heart disease as cholesterol levels are.
Persons with moderate or high levels of CRP can
often reduce the levels with lifestyle changes, including
quitting smoking, engaging in regular exercise, taking in
healthy nutrition, taking a multivitamin daily, replacing
saturated fats such as butter with monounsaturated
693

C-reactive protein

fats (particularly olive oil), increasing intake of
Omega-3 fatty acids, losing weight if overweight, and
increasing fiber intake. Drugs called statins (usually
used to reduce high levels of low density lipoproteins
(LDL), the so-called bad cholesterol, can also reduce
CRP levels. These drugs include: lovastatin (Mevacor),
simvastatin (Zocor), rosuvastatin (Crestor), and the two
drugs used in the 2005 CRP studies, pravastatin
(Pravacol) and atorvastatin (Lipitor). Other drugs that
lower CRP levels include the anti-cholesterol drug
ezetimibe (Zetia) and the diabetes medication rosiglitazone (Avandia).
Not all physicians are convinced the two studies
published in 2005 are accurate, noting that both
studies were funded by pharmaceutical companies
(Pfizer and Bristol-Meyer Squibb) that make statin
drugs used to reduce CRP levels. Also, the lead
authors of the studies have ‘‘strong financial ties to
the cardiac drug industry,’’ according to an article in
the February 2005 issue of HealthFacts. The article
also states that study participants already had severe
heart disease and in one study, 36% of the participants
smoked. It added that the CRP test is still unproven in
predicting future acute heart problems in people
with mild heart disease or healthy people at risk for
developing heart disease.
The C-reactive protein test costs $45 to $85, is
performed in physicians’ offices, labs, and hospitals.
Medicare usually covers the cost as do most other
insurance plans.

KEY TERMS
Atherosclerosis—A common artery disease in
which raised areas of degeneration and cholesterol deposits (plaques) form on the inner surfaces
of the arteries, often obstructing blood flow.
Hypertension—High blood pressure.
Low density lipoproteins (LDL)—A blood-plasma
lipoprotein that is high in cholesterol and low in
protein content and that carries cholesterol to cells
and tissue; also called bad cholesterol.
Omega-3 fatty acids—One of a group of beneficial fats found in oily fish, seeds, and whole grains.
Statins—A class of drugs commonly used to lower
LDL cholesterol levels.

Risks
There is an extremely slight risk of infection at the
needle puncture site.

Normal results
Normal test results are CRP levels of less than one
milligram (mg) per liter of blood. The ideal result is a
CRP level of zero.

Abnormal results
Preparation
No advance preparation for the CRP test is
needed on the part of the patient. The test is conducted
on a small sample of blood that usually takes about a
minute to withdraw from a patient’s vein. The CRP
test is performed in a laboratory and the results are
usually available in three to five days. A healthcare
professional, usually a nurse or laboratory technician,
will wrap and tighten a latex strap around the patient’s
upper arm. The site where blood will be drawn
(usually the bend in the arm above the elbow) will be
swabbed with alcohol. A small needle attached to a
collection vial will be inserted into a vein and a small
amount of blood will be withdrawn. When the vial is
full, the needle and strap will be removed and a cotton
ball will be taped over the injection site.

C-reactive protein levels of 1–3 mg per liter of
blood indicates a moderate risk of heart disease.
CRP levels above 3 mg per liter of blood indicates a
high risk for heart disease.
Resources
BOOKS

Deron, Scott J. C-Reactive Protein: Everything You Need to
Know About It and Why It’s More Important than
Cholesterol to Your Health. New York City:
McGraw-Hill, 2003.
Fleming, Dr. Richard M., and Tom Monte. Stop
Inflammation Now!: A Step-by-Step Plan to Prevent,
Treat, and Reverse Inflammation-The Leading Cause of
Heart Disease and Related Conditions. New York City:
G.P. Putnam’s Sons, 2004.
PERIODICALS

Aftercare
The tape and cotton can be removed when bleeding
at the needle puncture site stops, usually within 15 to 20
minutes. The amount of bleeding should be very light.
694

Abrams, Jonathan. ‘‘C-Reactive Protein Levels and
Outcomes after Statin Therapy.’’ Clinical Cardiology
Alert (March 2005): 17–19.
‘‘C-Reactive Protein Testing Not for Everyone.’’
HealthFacts (February 2005): 1.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Heart Association. 7272 Greenville Ave.,
Dallas, TX 75231. (800) 242-8721. <http://
www.americanheart.org>.
National Heart, Lung, and Blood Institute. Building 31,
Room 5A52, 31 Center Dr. MSC 2486, Bethesda, MD
20892. (301) 592-8573. <http://www.nhlbi.nih.gov>.

Ken R. Wells

C-section see Cesarean section
CABG surgery see Coronary artery bypass
graft surgery
CAD see Coronary artery disease

relievers, medicines for migraine headaches, and antihistamines also contain caffeine.

Recommended dosage
Adults and children age 12 years and over
100–200 mg no more than every 3–4 hours. In
timed-release form, the dose is 200–250 mg once a
day. Timed–release forms should not be taken less
than six hours before bedtime.
Children under 12 years
Not recommended.
Other considerations
People should avoid taking much caffeine when it
is being used as an over-the-counter drug and should
consider how much caffeine is being taken in from
coffee, tea, chocolate, soft drinks, and other foods
that contain caffeine. A pharmacist or physician
should be consulted to find out how much caffeine is
safe to use.

Precautions

I Caffeine
Definition
Caffeine is a drug that stimulates the central nervous system.

Purpose
Caffeine makes people more alert, less drowsy,
and improves coordination. Combined with certain
pain relievers or medicines for treating migraine headache, caffeine makes those drugs work more quickly
and effectively. Caffeine alone can also help relieve
headaches. Antihistamines are sometimes combined
with caffeine to counteract the drowsiness that those
drugs cause. Caffeine is also sometimes used to treat
other conditions, including breathing problems in
newborns and in young babies after surgery.

Description
Caffeine is found naturally in coffee, tea, and
chocolate. Colas and some other soft drinks contain
it. Caffeine also comes in tablet and capsule forms and
can be bought without a prescription. Over-the-counter caffeine brands include No Doz, Overtime, PepBack, Quick-Pep, Caffedrine, and Vivarin. Some pain
GALE ENCYCLOPEDIA OF MEDICINE

Caffeine cannot replace sleep and should not be
used regularly to stay awake as the drug can lead to
more serious sleep disorders, such as insomnia.
People who use large amounts of caffeine over long
periods build up a tolerance to it. When this happens,
they have to use more and more caffeine to get the same
effects. Heavy caffeine use can also lead to dependence.
If the person then stops using caffeine abruptly,
withdrawal symptoms may occur. These can include
throbbing headaches, fatigue, drowsiness, yawning,
irritability, restlessness, vomiting, or runny nose. These
symptoms can go on for as long as a week if caffeine is
avoided. Then the symptoms usually disappear. As of
2004, caffeine withdrawal has been officially recognized
as a disorder classification manual.
If taken too close to bedtime, caffeine can interfere
with sleep. Even if it does not prevent a person from
falling asleep, it may disturb sleep during the night.
The notion that caffeine helps people sober up
after drinking too much alcohol is a myth. In fact,
using caffeine and alcohol together is not a good
idea. The combination can lead to an upset stomach,
nausea, and vomiting.
Older people may be more sensitive to caffeine and
thus more likely to have certain side effects, such as
irritability, nervousness, anxiety, and sleep problems.
695

Caffeine

‘‘Get the C-Reactive Protein Test.’’ Medical Update
(February 2005): 3.
Spiker, Ted. ‘‘Bonfire of the Arteries.’’ Men’s Health
(December 2004): 114.
Zoler, Mitchel L. ‘‘Reducing CRP Is Key in Acute Coronary
Syndrome: Study Results Validate that Lowering CRP
Is Important, Even for Patients on a High-Dose
Statin.’’ Family Practice News (December 15, 2004): 15.

Caffeine

Special conditions
Caffeine may cause problems for people with certain medical conditions or who are taking certain
medicines.
ALLERGIES. Anyone with allergies to foods, dyes,
preservatives, or to the compounds aminophylline,
dyphylline, oxtriphylline, theobromine, or theophylline should check with a physician before using caffeine. Anyone who has ever had an unusual reaction to
caffeine should also check with a physician before
using it again.
PREGNANCY. Caffeine can pass from a pregnant
woman’s body into the developing fetus. Although
there is no evidence that caffeine causes birth defects
in people, it does cause such effects in laboratory
animals given very large doses (equal to human doses
of 12–24 cups of coffee a day). In humans, evidence
exists that doses of more than 300 mg of caffeine a day
(about the amount of caffeine in 2–3 cups of coffee)
may cause miscarriage or problems with the baby’s
heart rhythm. Women who take more than 300 mg
of caffeine a day during pregnancy are also more likely
to have babies with low birth weights. Any woman
who is pregnant or planning to become pregnant
should check with her physician before using caffeine.
BREASTFEEDING. Caffeine passes into breast milk
and can affect the nursing baby. Nursing babies whose
mothers use 600 mg or more of caffeine a day may be
irritable and have trouble sleeping. Women who are
breastfeeding should check with their physicians
before using caffeine.
OTHER MEDICAL CONDITIONS. Caffeine may cause
problems for people with these medical conditions:


peptic ulcer



heart arrhythmias or palpitations



heart disease or recent heart attack (within a few
weeks)



high blood pressure



liver disease



insomnia (trouble sleeping)



anxiety or panic attacks



agoraphobia (fear of being in open places)



premenstrual syndrome (PMS)

USE OF CERTAIN MEDICINES. Using caffeine with
certain other drugs may interfere with the effects of
the drugs or cause unwanted—and possibly serious—
side effects.

696

KEY TERMS
Arrhythmia—Abnormal heart rhythm.
Central nervous system—The brain and spinal cord.
Fetus—A developing baby inside the womb.
Palpitation—Rapid, forceful, throbbing, or fluttering
heartbeat.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug to which he or she has
become dependent.

Side effects
At recommended doses, caffeine can cause restlessness, irritability, nervousness, shakiness, headache,
lightheadedness, sleeplessness, nausea, vomiting, and
upset stomach. At higher than recommended doses,
caffeine can cause excitement, agitation, anxiety,
confusion, a sensation of light flashing before the
eyes, unusual sensitivity to touch, unusual sensitivity
of other senses, ringing in the ears, frequent urination,
muscle twitches or tremors, heart arrhythmias, rapid
heartbeat, flushing, and convulsions. High caffeine
consumption can lead to benign breast disease, which
also can increase risk of breast cancer.

Interactions
Certain drugs interfere with the breakdown of
caffeine in the body. These include oral contraceptives
that contain estrogen, the antiarrhythmia drug mexiletine (Mexitil), the ulcer drug cimetidine (Tagamet),
and the drug disulfiram (Antabuse), used to treat
alcoholism.
Caffeine interferes with drugs that regulate heart
rhythm, such as quinidine and propranolol (Inderal).
Caffeine may also interfere with the body’s absorption
of iron. Anyone who takes iron supplements should
take them at least an hour before or two hours after
using caffeine.
Serious side effects are possible when caffeine is
combined with certain drugs. For example, taking caffeine with the decongestant phenylpropanolamine can
raise blood pressure. And serious heart problems may
occur if caffeine and monoamine oxidase inhibitors
(MAO) are taken together. These drugs are used to
treat Parkinson’s disease, depression, and other psychiatric conditions. A pharmacist or physician should be
consulted about which drugs can interact with caffeine.
GALE ENCYCLOPEDIA OF MEDICINE

should and will watch for unwanted side effects.
People who have high blood pressure often feel perfectly fine. However, they should continue to see their
prescribing physician even when they feel well so that
he can keep a close watch on their condition. They
should also continue to take their medicine even when
they feel fine.

Resources

Calcium channel blockers will not cure high blood
pressure, but will help to control the condition. To
avoid the serious health problems associated with
high blood pressure, patients may have to take this
type of medication for the rest of their lives.
Furthermore, the blockers alone may not be enough.
People with high blood pressure may also need to
avoid certain foods and keep their weight under control. The health care professional who is treating the
condition can offer advice as to what measures may be
necessary. Patients being treated for high blood pressure should not change their diets without consulting
their physicians.

PERIODICALS

‘‘Caffeine Withdrawal Recognized as Disorder.’’ Ascribe
Health News Service September 29, 2004.
‘‘High Caffeine Intake May Increase Risk of Benign Breast
Disease.’’ Womenós Health Weekly September 16,
2004: 32.

Nancy Ross-Flanigan
Teresa G. Odle

CAH see Congenital adrenal hyperplasia
Caisson disease see Decompression sickness
Calcaneal spurs see Heel spurs
Calcitonin see Bone disorder drugs
Calcium carbonate see Antacids

I Calcium channel blockers
Definition
Calcium channel blockers are medicines that slow
the movement of calcium into the cells of the heart and
blood vessels. This, in turn, relaxes blood vessels,
increases the supply of oxygen-rich blood to the
heart, and reduces the heart’s workload.

Purpose
Calcium channel blockers are used to treat high
blood pressure, to correct abnormal heart rhythms,
and to relieve the type of chest pain called angina
pectoris. Physicians also prescribe calcium channel
blockers to treat panic attacks and bipolar disorder
(manic depressive illness) and to prevent migraine
headache.

Precautions
Seeing a physician regularly while taking calcium
channel blockers is important. The physician will
check to make certain the medicine is working as it
GALE ENCYCLOPEDIA OF MEDICINE

Anyone taking calcium channel blockers for high
blood pressure should not take any other prescription
or over-the-counter medication without first checking
with the prescribing physician, as some of these drugs
may increase blood pressure.
Some people feel drowsy or less alert than usual
when taking calcium channel blockers. Anyone who
takes these drugs should not drive, use machines, or do
anything else that might be dangerous until they have
found out how the drugs affect them.
People who normally have chest pain when they
exercise or exert themselves may not have the pain
when they are taking calcium channel blockers. This
could lead them to be more active than they should be.
Anyone taking calcium channel blockers should therefore consult with the prescribing physician concerning
how much exercise and activity may be considered
safe.
Some people get headaches that last for a short
time after taking a dose of this medication. This problem usually goes away during the course of treatment. If it does not, or if the headaches are severe,
the prescribing physician should be informed.
Patients taking certain calcium channel blockers
may need to check their pulse regularly, as the drugs
may slow the pulse too much. If the pulse is too slow,
circulation problems may result. The prescribing physician can show patients the correct way to check their
pulse.
This type of medication may cause the gums to
swell, bleed, or become tender. If this problem occurs,
697

Calcium channel blockers

Because caffeine stimulates the nervous system,
anyone taking other central nervous system (CNS)
stimulants should be careful about using caffeine.
Those trying to withdraw from caffeine are advised
to do reduce their consumption slowly over time
by substituting decaffeinated or non-caffeinated
products for some of the caffeinated products.

Calcium channel blockers

a medical physician or dentist should be consulted. To
help prevent the problem, care should be taken when
brushing and flossing the teeth. Regular dental checkups and cleanings are also recommended.
Older people may be unusually sensitive to the
effects of calcium channel blockers. This may increase
the chance of side effects.
Special conditions
People with certain medical conditions or who are
taking certain other medicines may develop problems
if they also take calcium channel blockers. Before
taking these drugs, the prescribing physician should
be informed about any of these conditions:
ALLERGIES. Anyone who has had a previous unusual reaction to any calcium channel blocker should
let his or her physician know before taking the drugs
again. The physician should also be notified about any
allergies to foods, dyes, preservatives, or other
substances.
PREGNANCY. The effects of taking calcium channel blockers during pregnancy have not been studied in
humans. However, in studies of laboratory animals,
large doses of these drugs have been reported to cause
birth defects, stillbirth, poor bone growth, and other
problems when taken during pregnancy. Women who
are pregnant or who may become pregnant should
check with their physicians before using these drugs.
BREASTFEEDING. Some calcium channel blockers
pass into breast milk, but there have been no reports
of problems in nursing babies whose mothers were
taking this type of medication. However, women
who need to take this medicine and want to breastfeed
their babies should check with their physicians.
OTHER MEDICAL CONDITIONS. Calcium channel
blockers may worsen heart or blood vessel disorders.

Side effects
Side effects are not common with this medicine,
but some may occur. Minor discomforts, such as dizziness, lightheadedness, flushing, headache, and nausea,
usually go away as the body adjusts to the drug and do
not require medical treatment unless they persist or
they are bothersome.
If any of the following side effects occur, the prescribing physician should be notified as soon as
possible:


breathing problems, coughing or wheezing



irregular, fast, or pounding heartbeat



slow heartbeat (less than 50 beats per minute)



skin rash



swollen ankles, feet, or lower legs

Other side effects may occur. Anyone who has
unusual symptoms after taking calcium blockers
should contact the prescribing physician.
Interactions
Calcium channel blockers may interact with a
number of other medications. When this happens,
the effects of one or both of the drugs may change or
the risk of side effects may increase. Anyone who takes
calcium channel blockers should not take any other
prescription or nonprescription (over-the-counter)
medicines without first checking with the prescribing
physician. Substances that may interact with calcium
channel blockers include:


Diuretics (water pills). This type of medicine may
cause low levels of potassium in the body, which
may increase the chance of unwanted effects from
some calcium channel blockers.



Beta-blockers, such as atenolol (Tenormin), propranolol (Inderal), and metoprolol (Lopressor), used to
treat high blood pressure, angina, and other conditions. Also, eye drop forms of beta blockers, such as
timolol (Timoptic), used to treat glaucoma. Taking any
of these drugs with calcium channel blockers may
increase the effects of both types of medicine and
may cause problems if either drug is stopped suddenly.



Digitalis heart medicines. Taking these medicines
with calcium channel blockers may increase the
action of the heart medication.



Medicines used to correct irregular heart rhythms,
such as quinidine (Quinidex), disopyramide
(Norpace), and procainamide (Procan, Pronestyl).
The effects of these drugs may increase if used with
calcium channel blockers.

The effects of calcium channel blockers may be
greater in people with kidney or liver disease, as their
bodies are slower to clear the drug from their systems.
Certain calcium channel blockers may also cause
problems in people with a history of heart rhythm
problems or with depression, Parkinson’s disease, or
other types of parkinsonism.
USE OF CERTAIN MEDICINES. Taking calcium chan-

nel blockers with certain other drugs may affect the
way the drugs work or may increase the chance of side
effects.
As with most medications, certain side effects are
possible and some interactions with other substances
may occur.
698

GALE ENCYCLOPEDIA OF MEDICINE

Anti-seizure medications such as carbamazepine
(Tegretol). Calcium channel drugs may increase the
effects of these medicines.



Cyclosporine (Sandimmune), a medicine that suppresses the immune system. Effects may increase if
this drug is taken with calcium channel blockers.



Grapefruit juice may increase the effects of some
calcium channel blockers.

The above list does not include every drug that
may interact with calcium channel blockers. The
prescribing physician or pharmacist will advise as to
whether combining calcium channel blockers with any
other prescription or nonprescription (over-thecounter) medication is appropriate or not.

KEY TERMS
Angina pectoris—A feeling of tightness, heaviness,
or pain in the chest, caused by a lack of oxygen in
the muscular wall of the heart.
Bipolar disorder—A severe mental illness, also
known as manic depression, in which a person
has extreme mood swings, ranging from a highly
excited state—sometimes with a false sense of
well–being—to depression.
Migraine—A throbbing headache that usually
affects only one side of the head. Nausea, vomiting,
increased sensitivity to light, and other symptoms
often accompany migraine.

Description
Calcium channel blockers are available only with
a physician’s prescription and are sold in tablet, capsule, and injectable forms. Some commonly used calcium channel blockers include amlopidine (Norvasc),
diltiazem (Cardizem), isradipine (DynaCirc), nifedipine (Adalat, Procardia), nicardipine (Cardene), and
verapamil (Calan, Isoptin, Verelan).
The recommended dosage depends on the type,
strength, and form of calcium channel blocker and the
condition for which it is prescribed. Correct dosage is
determined by the prescribing physician and further
information can be obtained from the pharmacist.
Calcium channel blockers should be taken as
directed. Larger or more frequent doses should not
be taken, nor should doses be missed. This medicine
may take several weeks to noticeably lower blood
pressure. The patient taking calcium channel blockers
should keep taking the medicine, to give it time to
work. Once it begins to work and symptoms improve,
it should continue to be taken as prescribed.
This medicine should not be discontinued without
checking with the prescribing physician. Some conditions may worsen when patients stop taking calcium
channel blockers abruptly. The prescribing physician
will advise as to how to gradually taper down before
stopping the medication completely.

Risks
A report from the European Cardiology Society
in 2000 found that patients taking certain calcium
channel blockers had a 27% greater risk of heart
attack, and a 26% greater risk of heart failure than
patients taking other high blood pressure medicines.
However, there are many patients affected by
GALE ENCYCLOPEDIA OF MEDICINE

conditions that still make calcium channel blockers
the best choice for them. The patient should discuss
this issue with the prescribing physician.

Normal results
The expected result of taking a calcium channel
blocker is to either correct abnormal heart rhythms,
return blood pressure to normal, or relieve chest pain.
Resources
BOOKS

Beers, Mark H., and Robert Berkow, editors. The Merck
Manual of Diagnosis and Therapy. 17th ed. Whitehouse
Station, NJ: Merck and Company, Inc., 1999.
PERIODICALS

‘‘The Pressure’s On: A Hypertension Drug Taken by 28
Million People is Under Scrutiny. What Are the Other
Options? (Calcium Channel Blockers).’’ Time
September 11, 2000:126.
Zoler, Mitchel L. ‘‘Drug Update: Calcium Channel Blockers
For Hypertension.’’ Family Practice News April 1,
2000: 53.

Deanna M. Swartout-Corbeil, R.N.

Calcium imbalance see Hypercalcemia;
Hypocalcemia
Calcium polycarbophil see Laxatives
California flower essences see Flower
remedies
Calluses see Corns and calluses
Calorie-modified diet see Diets
699

Calcium channel blockers



Campylobacteriosis

Calymmatobacteriosis see Granuloma
inguinale
Campylobacter jejuni infection see
Campylobacteriosis

I Campylobacteriosis
Definition
Campylobacteriosis refers to infection by the
group of bacteria known as Campylobacter. The term
comes from the Greek word meaning ‘‘curved rod’’
referring to the bacteria’s curved shape. The most common disease caused by these organisms is diarrhea,
which most often affects children and younger adults.
Campylobacter infections account for a substantial percent of food-borne illness encountered each year.

Complications
Dehydration is the most common complication.
Especially at the extremes of age, this should be
watched for and treated with either Oral Rehydration
Solution or intravenous fluid replacement.
Infection may also involve areas outside the intestine. This is unusual, except for infections with
C. fetus. C. fetus infections tend to occur in those
who have diseases of decreased immunity such as
AIDS, cancer, etc. This subtype is particularly
adapted to protect itself from the body’s defenses.
Areas outside the intestine that may be involved are:


Nervous system involvement either by direct infection
of the meninges (outer covering of the spinal and
brain) or more commonly by producing the GuillainBarré syndrome (progressive and reversible paralysis
or weakness of many muscles). In fact, Campylobacter
may be responsible for 40% of the reported cases of
this syndrome.



Joint inflammation can occur weeks later (leading to
an unusual form of arthritis).



Infection of vessels and heart valves is a special characteristic of C. fetus. Immunocompromised patients
may develop repeated episodes of passage of bacteria
into the bloodstream from these sites of infection.



The gallbladder, pancreas, and bone may be affected.

Description
There are over 15 different subtypes, all of which
are curved Gram-negative rods. C. jeuni is the subtype
that most often causes gastrointestinal disease.
However, some species such as C. fetus produce disease outside the intestine, particularly in those with
altered immune systems, such as people with AIDS,
cancer, and liver disease.
Campylobacter are often found in the intestine of
animals raised for food produce and pets. Infected animals often have no symptoms. Chickens are the most
common source of human infection. It is estimated
that 1% of the general population is infected each year.

Causes and symptoms
Improper or incomplete food preparation is the
most common way the disease is spread, with poultry
accounting for over half the cases. Untreated water
and raw milk are also potential sources.
The incubation period after exposure is from one
to 10 days. A day or two of mild fever, muscle aches,
and headache occur before intestinal symptoms begin.
Diarrhea with or without blood and severe abdominal
cramps are the major intestinal symptoms. The severity of symptoms is variable, ranging from only mild
fever to dehydration and rarely death (mainly in the
very young or old). The disease usually lasts about one
week, but persists longer in about 20% of cases. At
least 10% will have a relapse, and some patients will
continue to pass the bacteria for several weeks.
700

Diagnosis
Campylobacter is only one of many causes of
acute diarrhea. Culture (growing the bacteria in the
laboratory) of freshly obtained diarrhea fluid is the
only way to be certain of the diagnosis.

Treatment
The first aim of treatment is to keep up nutrition
and avoid dehydration. Medications used to treat
diarrhea by decreasing intestinal motility, such as
Loperamide or Diphenoxylate are also useful, but
should only be used with the advice of a physician.
Antibiotics are of value, if started within three days of
onset of symptoms. They are indicated for those with
severe or persistent symptoms. Either an erythromycin
type drug or one of the fluoroquinolones (such as ciprofloxacin) for five to seven days are the accepted
therapies.

Prognosis
Most patients with Campylobacter infection
rapidly recover without treatment. For certain groups
GALE ENCYCLOPEDIA OF MEDICINE

Antibiotic—A medication that is designed to kill or
weaken bacteria.
Anti-motility medications—Medications such as
loperamide (Imodium), dephenoxylate (Lomotil),
or medications containing codeine or narcotics
which decrease the ability of the intestine to contract. This can worsen the condition of a patient
with dysentery or colitis.
Fluoroquinolones—A relatively new group of antibiotics that have had good success in treating infections with many Gram-negative bacteria. One
drawback is that they should not be used in children under 17 years of age, because of possible
effect on bone growth.
Food-borne illness—A disease that is transmitted
by eating or handling contaminated food.
Gram-negative—Refers to the property of many
bacteria that causes them to not take up color
with Gram’s stain, a method which is used to identify bacteria. Gram-positive bacteria which take up
the stain turn purple, while Gram-negative bacteria
which do not take up the stain turn red.
Guillain-Barré syndrome—Progressive and usually
reversible paralysis or weakness of multiple muscles usually starting in the lower extremities and
often ascending to the muscles involved in respiration. The syndrome is due to inflammation and loss
of the myelin covering of the nerve fibers, often
associated with an acute infection.
Meninges—Outer covering of the spinal cord and
brain. Infection is called meningitis, which can lead
to damage to the brain or spinal cord and even death.
Oral Rehydration Solution (ORS)—A liquid
preparation developed by the World Health
Organization that can decrease fluid loss in persons
with diarrhea. Originally developed to be prepared
with materials available in the home, commercial
preparations have recently come into use.
Stool—Passage of fecal material; a bowel movement.

of patients, infection becomes chronic and requires
repeated courses of antibiotics.

Prevention
Good hand washing technique as well as proper
preparation and cooking of food is the best way to
prevent infection.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
OTHER

Centers for Disease Control. <http://www.cdc.gov/
nccdphp/ddt/ddthome.htm>.

David Kaminstein, MD

I Cancer
Definition
Cancer is not just one disease, but a large group of
almost 100 diseases. Its two main characteristics are
uncontrolled growth of the cells in the human body
and the ability of these cells to migrate from the
original site and spread to distant sites. If the spread
is not controlled, cancer can result in death.

Description
One out of every four deaths in the United States
is from cancer. It is second only to heart disease as a
cause of death in the states. About 1.2 million
Americans are diagnosed with cancer annually; more
than 500,000 die of cancer annually.
Cancer can attack anyone. Since the occurrence of
cancer increases as individuals age, most of the cases
are seen in adults, middle-aged or older. Sixty percent
of all cancers are diagnosed in people who are older
than 65 years of age. The most common cancers are
skin cancer, lung cancer, colon cancer, breast cancer (in
women), and prostate cancer (in men). In addition,
cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and blood and lymph node cancer (leukemias and lymphomas) are also included among the
12 major cancers that affect most Americans.
Cancer, by definition, is a disease of the genes.
A gene is a small part of DNA, which is the master
molecule of the cell. Genes make ‘‘proteins,’’ which are
the ultimate workhorses of the cells. It is these proteins
that allow our bodies to carry out all the many
processes that permit us to breathe, think, move, etc.
Throughout people’s lives, the cells in their bodies
are growing, dividing, and replacing themselves.
Many genes produce proteins that are involved in
controlling the processes of cell growth and division.
701

Cancer

Resources

KEY TERMS

Cancer

J A N E T D . R O W L E Y (1925– )
Janet Davison Rowley was born in New York City on
April 5, 1925, to Ethel Mary (Ballantyne) and Hurford
Henry Davison. Rowley attended the University of
Chicago, earning her B.S. degree in 1946 and her M.D.
degree in 1948. She also married Donald A. Rowley in
1948, and the couple ultimately had four sons. Rowley
completed both her internship and residency at Chicago
hospitals before returning to the University of Chicago
Medical School where she conducted research from
1962-1969. She became an associate professor, and
finally, in 1977, earned her position as a full professor.
Rowley’s research has focused on understanding
cancer, with special emphasis on its cytogenetic causes.
Her development and use of Giemsa and quinacrine
stains enabled Rowley to discover oncogenes and to
ultimately show a consistent shifting or translocation of
genetic material in chronic myeloid leukemia cells.
Rowley’s discoveries and continued research have
shown that malignant cells in humans undergo this translocation and deletion of genes that cause tumors to grow.
Her research has given oncologists new pathways to
explore concerning gene therapies for the treatment of
cancer.

body. If the cancer cells have spread to the surrounding tissues, even after the malignant tumor is removed,
it generally recurs.
A majority of cancers are caused by changes in the
cell’s DNA because of damage due to the environment. Environmental factors that are responsible for
causing the initial mutation in the DNA are called
carcinogens, and there are many types.
There are some cancers that have a genetic basis.
In other words, an individual could inherit faulty
DNA from his parents, which could predispose him
to getting cancer. While there is scientific evidence that
both factors (environmental and genetic) play a role,
less than 10% of all cancers are purely hereditary.
Cancers that are known to have a hereditary link are
breast cancer, colon cancer, ovarian cancer, and uterine cancer. Besides genes, certain physiological traits
could be inherited and could contribute to cancers.
For example, inheriting fair skin makes a person
more likely to develop skin cancer, but only if he or
she also has prolonged exposure to intensive sunlight.
There are several different types of cancers:


Carcinomas are cancers that arise in the epithelium
(the layer of cells covering the body’s surface and
lining the internal organs and various glands).
Ninety percent of human cancers fall into this category. Carcinomas can be subdivided into two types:
adenocarcinomas and squamous cell carcinomas.
Adenocarcinomas are cancers that develop in an
organ or a gland, while squamous cell carcinomas
refer to cancers that originate in the skin.



Melanomas also originate in the skin, usually in the
pigment cells (melanocytes).



Sarcomas are cancers of the supporting tissues of the
body, such as bone, muscle and blood vessels.



Cancers of the blood and lymph glands are called
leukemias and lymphomas respectively.



Gliomas are cancers of the nerve tissue.

Co-editor and co-founder of the journal, Genes,
Chromosomes and Cancer, Rowley has published an
abundance of materials including Chromosome
Changes in Leukemia (1978), Genes and Cancer (1984),
and Advances in Understanding Genetic Changes in
Cancer (1992). Rowley has also received many awards
and honors for her work and research.

An alteration (mutation) to the DNA molecule can
disrupt the genes and produce faulty proteins. This
causes the cell to become abnormal and lose its
restraints on growth. The abnormal cell begins to
divide uncontrollably and eventually forms a new
growth known as a ‘‘tumor’’ or neoplasm (medical
term for cancer meaning ‘‘new growth’’).
In a healthy individual, the immune system can
recognize the neoplastic cells and destroy them before
they get a chance to divide. However, some mutant
cells may escape immune detection and survive to
become tumors or cancers.
Tumors are of two types, benign or malignant. A
benign tumor is not considered cancer. It is slow growing, does not spread or invade surrounding tissue, and
once it is removed, doesn’t usually recur. A malignant
tumor, on the other hand, is cancer. It invades
surrounding tissue and spreads to other parts of the
702

Causes and symptoms
The major risk factors for cancer are: tobacco,
alcohol, diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment
and pollution.
According to estimates of the American Cancer
Society (ACS), approximately 40% of cancer deaths in
1998 were due to tobacco and excessive alcohol use.
An additional one-third of the deaths were related to
diet and nutrition. Many of the one million skin
GALE ENCYCLOPEDIA OF MEDICINE

Cancer Site

Number of Deaths Per Year

Lung
Colon and rectum
Breast
Prostate
Pancreas
Lymphoma
Leukemia
Brain
Stomach
Liver
Esophagus
Bladder
Kidney
Multiple myeloma

160,100
56,500
43,900
39,200
28,900
26,300
21,600
17,400
13,700
13,000
11,900
12,500
11,600
11,300

cancers diagnosed in 1998 were due to over-exposure
to ultraviolet light from the sun’s rays.
Tobacco
Eighty to 90% of lung cancer cases occur in
smokers. Smoking has also been shown to be a contributory factor in cancers of upper respiratory tract, esophagus, larynx, bladder, pancreas, and probably liver,
stomach, breast, and kidney as well. Recently, scientists
have also shown that second-hand smoke (or passive
smoking) can increase one’s risk of developing cancer.
Alcohol
Excessive consumption of alcohol is a risk factor
in certain cancers, such as liver cancer. Alcohol, in
combination with tobacco, significantly increases the
chances that an individual will develop mouth, pharynx, larynx, and esophageal cancers.
Diet
Thirty–five percent of all cancers are due to dietary causes. Excessive intake of fat leading to obesity
has been associated with cancers of the breast, colon,
rectum, pancreas, prostate, gall bladder, ovaries, and
uterus.
Sexual and reproductive behavior
The human papillomavirus, which is sexually
transmitted, has been shown to cause cancer of the
cervix. Having too many sex partners and becoming
sexually active early has been shown to increase one’s
chances of contracting this disease. In addition, it has
GALE ENCYCLOPEDIA OF MEDICINE

Infectious agents
In the last 20 years, scientists have obtained evidence to show that approximately 15% of the world’s
cancer deaths can be traced to viruses, bacteria, or
parasites. The most common cancer-causing pathogens and the cancers associated with them are shown
in table form.
Family history
Certain cancers like breast, colon, ovarian, and
uterine cancer recur generation after generation in
some families. A few cancers, such as the eye cancer
‘‘retinoblastoma,’’ a type of colon cancer, and a type
of breast cancer known as ‘‘early-onset breast cancer,’’
have been shown to be linked to certain genes that can
be tracked within a family. It is therefore possible that
inheriting particular genes makes a person susceptible
to certain cancers.
Occupational hazards
There is evidence to prove that certain occupational hazards account for 4% of all cancer deaths.
For example, asbestos workers have an increased incidence of lung cancer. Similarly, a higher likelihood of
getting bladder cancer is associated with dye, rubber
and gas workers; skin and lung cancer with smelters,
gold miners and arsenic workers; leukemia with glue
and varnish workers; liver cancer with PVC manufacturers; and lung, bone and bone marrow cancer with
radiologists and uranium miners.
Environment
Radiation is believed to cause 1–2% of all cancer
deaths. Ultra-violet radiation from the sun accounts
for a majority of melanoma deaths. Other sources of
radiation are x rays, radon gas, and ionizing radiation
from nuclear material.
Pollution
Several studies have shown that there is a wellestablished link between asbestos and cancer.
Chlorination of water may account for a small rise in
cancer risk. However, the main danger from pollution
occurs when dangerous chemicals from the industries
escape into the surrounding environment. It has been
estimated that 1% of cancer deaths are due to air,
land, and water pollution.
703

Cancer

also been shown that women who don’t have children
or have children late in life have an increased risk for
both ovarian and breast cancer.

Frequency Of Cancer-Related Death

Cancer

COMMON PATHOGENS AND THE CANCERS ASSOCIATED WITH THEM

Despite the fact that there are several hundred
different types of cancers, producing very different
symptoms, the ACS has established the following
seven symptoms as possible warning signals of cancer:

Causative Agent



changes in the size, color, or shape of a wart or a mole



a sore that does not heal



persistent cough, hoarseness, or sore throat



a lump or thickening in the breast or elsewhere



unusual bleeding or discharge



chronic indigestion or difficulty in swallowing



any change in bowel or bladder habits

Type of Cancer

Viruses
Papillomaviruses
Hepatitis B virus
Hepatitis C virus
Epstein-Barr virus
Cancers of the upper
pharynx
Human
immunodeficiency
virus (HIV)
Bacteria

Cancer of the cervix
Liver cancer
Liver cancer
Burkitt’s lymphoma
Hodgkin’s lymphoma, Non-Hodgkin’s
lymphoma, Gastric cancers
Kaposi’s sarcoma Lymphoma

Helicobacter pylori

Stomach cancer Lymphomas

Many other diseases, besides cancer, could
produce the same symptoms. However, it is important
to have these symptoms checked, as soon as possible,
especially if they linger. The earlier a cancer is
diagnosed and treated, the better the chance of it
being cured. Many cancers such as breast cancer
may not have any early symptoms. Therefore, it is
important to undergo routine screening tests such as
breast self-exams and mammograms.

Diagnosis
Diagnosis begins with a thorough physical examination and a complete medical history. The doctor
will observe, feel and palpate (apply pressure by
touch) different parts of the body in order to identify
any variations from the normal size, feel, and texture
of the organ or tissue.

A transmission electron micrograph (TEM) of two spindle cell
nuclei from a human sarcoma. Sarcomas are cancers of the
connective tissue (bone, nerves, smooth muscle).
(Photograph by Dr. Brian Eyden, Photo Researchers, Inc.
Reproduced by permission.)

Cancer is a progressive disease, and goes
through several stages. Each stage may produce
a number of symptoms. Some symptoms are produced early and may occur due to a tumor that is
growing within an organ or a gland. As the tumor
grows, it may press on the nearby nerves, organs,
and blood vessels. This causes pain and some pressure which may be the earliest warning signs of
cancer.
704

As part of the physical exam, the doctor will
inspect the oral cavity, or the mouth. By focusing a
light into the mouth, he will look for abnormalities in
color, moisture, surface texture, or presence of any
thickening or sore in the lips, tongue, gums, the hard
palate on the roof of the mouth, and the throat. To
detect thyroid cancer, the doctor will observe the front
of the neck for swelling. He may gently manipulate the
neck and palpate the front and side surfaces of the
thyroid gland (located at the base of the neck) to detect
any nodules or tenderness. As part of the physical
examination, the doctor will also palpate the lymph
nodes in the neck, under the arms and in the groin.
Many illnesses and cancers cause a swelling of the
lymph nodes.
The doctor may conduct a thorough examination
of the skin to look for sores that have been present for
more than three weeks and that bleed, ooze, or crust;
irritated patches that may itch or hurt, and any change
in the size of a wart or a mole.
GALE ENCYCLOPEDIA OF MEDICINE

For males, inspection of the rectum and the prostate is also included in the physical examination. The
doctor inserts a gloved finger into the rectum and
rotates it slowly to feel for any growths, tumors, or
other abnormalities. The doctor also conducts an
examination of the testes, where the doctor observes
the genital area and looks for swelling or other
abnormalities. The testicles are palpated to identify
any lumps, thickening or differences in the size, weight
and firmness.
If the doctor detects an abnormality on physical
examination, or the patient has some symptom that
could be indicative of cancer, the doctor may order
diagnostic tests.
Laboratory studies of sputum (sputum cytology),
blood, urine, and stool can detect abnormalities that
may indicate cancer. Sputum cytology is a test where
the phlegm that is coughed up from the lungs is microscopically examined. It is often used to detect lung
cancer. A blood test for cancer is easy to perform,
usually inexpensive and risk-free. The blood sample
is obtained by a lab technician or a doctor by inserting
a needle into a vein and is relatively painless. Blood
tests can be either specific or non-specific. Often, in
certain cancers, the cancer cells release particular proteins (called tumor markers) and blood tests can be
used to detect the presence of these tumor markers.
However, with a few exceptions, tumor markers are
not used for routine screening of cancers, because
several non-cancerous conditions also produce positive results. Blood tests are generally more useful in
monitoring the effectiveness of the treatment, or in
following the course of the disease and detecting recurrent disease.
Imaging tests such as computed tomography scans
(CT scans), magnetic resonance imaging (MRI), ultrasound and fiberoptic scope examinations help the doctors determine the location of the tumor even if it is
deep within the body. Conventional x rays are often
used for initial evaluation, because they are relatively
cheap, painless and easily accessible. In order to
increase the information obtained from a conventional
GALE ENCYCLOPEDIA OF MEDICINE

x ray, air or a dye (such as barium or iodine) may be
used as a contrast medium to outline or highlight parts
of the body.
The most definitive diagnostic test is the biopsy,
wherein a piece of tissue is surgically removed for
microscope examination. Besides confirming a cancer,
the biopsy also provides information about the type of
cancer, the stage it has reached, the aggressiveness of
the cancer and the extent of its spread. Since a biopsy
provides the most accurate analysis, it is considered
the gold standard of diagnostic tests.
Screening examinations conducted regularly by
healthcare professionals can result in the detection of
cancers of the breast, colon, rectum, cervix, prostate,
testis, tongue, mouth, and skin at early stages, when
treatment is more likely to be successful. Some of the
routine screening tests recommended by the ACS are
sigmoidoscopy (for colorectal cancer), mammography
(for breast cancer), pap smear (for cervical cancer),
and the PSA test (for prostate cancer). Self-examinations for cancers of the breast, testes, mouth, and skin
can also help in detecting the tumors before the symptoms become serious.
A recent revolution in molecular biology and cancer genetics has contributed a great deal to the development of several tests designed to assess one’s risk of
getting cancers. These new techniques include genetic
testing, where molecular probes are used to identify
mutations in certain genes that have been linked to
particular cancers. At present, however, there are a lot
of limitations to genetic testing and its utility appears
ambiguous, emphasizing the need to develop better
strategies for early detection.

Treatment
Treatment and prevention of cancers continue to
be the focus of a great deal of research. In 2003,
research into new cancer therapies included cancertargeting gene therapy, virus therapy, and a drug that
stimulated apoptosis, or self-destruction of cancer
cells, but not healthy cells. However, all of these new
therapies take years of clinical testing and research.
The aim of cancer treatment is to remove all or as
much of the tumor as possible and to prevent the
recurrence or spread of the primary tumor. While
devising a treatment plan for cancer, the likelihood
of curing the cancer has to be weighed against the
side effects of the treatment. If the cancer is very
aggressive and a cure is not possible, then the treatment should be aimed at relieving the symptoms and
controlling the cancer for as long as possible.
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Cancer

Examination of the female pelvis is used to detect
cancers of the ovaries, uterus, cervix, and vagina. In
the visual examination, the doctor looks for abnormal
discharges or the presence of sores. Then, using gloved
hands the physician palpates the internal pelvic organs
such as the uterus and ovaries to detect any abnormal
masses. Breast examination includes visual observation where the doctor looks for any discharge, unevenness, discoloration, or scaling. The doctor palpates
both breasts to feel for masses or lumps.

Cancer

Cancer treatment can take many different forms,
and it is always tailored to the individual patient. The
decision on which type of treatment is the most appropriate depends on the type and location of cancer, the
extent to which it has already spread, the patient’s age,
sex, general health status and personal treatment preferences. The major types of treatment are: surgery,
radiation, chemotherapy, immunotherapy, hormone
therapy, and bone-marrow transplantation.

symptoms. In tumors that are dependent on hormones, removal of the organs that secrete the hormones is an option. For example, in prostate cancer,
the release of testosterone by the testicles stimulates the
growth of cancerous cells. Hence, a man may undergo
an ‘‘orchiectomy’’ (removal of testicles) to slow the
progress of the disease. Similarly, in a type of aggressive breast cancer, removal of the ovaries (oophorectomy) will stop the synthesis of hormones from the
ovaries and slow the progression of the cancer.

Surgery
Surgery is the removal of a visible tumor and is the
most frequently used cancer treatment. It is most
effective when a cancer is small and confined to one
area of the body.
Surgery can be used for many purposes.




Treatment. Treatment of cancer by surgery involves
removal of the tumor to cure the disease. This is
typically done when the cancer is localized to a discrete area. Along with the cancer, some part of the
normal surrounding tissue is also removed to ensure
that no cancer cells remain in the area. Since cancer
usually spreads via the lymphatic system, adjoining
lymph nodes may be examined and sometimes are
removed as well.
Preventive surgery. Preventive or prophylactic surgery involves removal of an abnormal looking area
that is likely to become malignant over time. For
example, 40% of people with a colon disease
known as ulcerative colitis, ultimately die of colon
cancer. Rather than live with the fear of developing
colon cancer, these people may choose to have their
colons removed and reduce the risk significantly.



Diagnostic purposes. The most definitive tool for
diagnosing cancer is a biopsy. Sometimes, a biopsy
can be performed by inserting a needle through the
skin. However, at other times, the only way to
obtain a tissue sample for biopsy is by performing
a surgical operation.



Cytoreductive surgery is a procedure where the doctor removes as much of the cancer as possible, and
then treats the remaining area with radiation therapy
or chemotherapy or both.



Palliative surgery is aimed at curing the symptoms, not
the cancer. Usually, in such cases, the tumor is so large
or has spread so much that removing the entire tumor
is not an option. For example, a tumor in the abdomen
may be so large that it may press on and block a
portion of the intestine, interfering with digestion and
causing pain and vomiting. ‘‘Debulking surgery’’ may
remove a part of the blockage and relieve the

706

Radiation therapy
Radiation kills tumor cells. Radiation is used
alone in cases where a tumor is unsuitable for surgery.
More often, it is used in conjunction with surgery and
chemotherapy. Radiation can be either external or
internal. In the external form, the radiation is aimed
at the tumor from outside the body. In internal radiation (also known as brachytherapy), a radioactive
substance in the form of pellets or liquid is placed at
the cancerous site by means of a pill, injection or
insertion in a sealed container.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer
cells. It destroys the hard-to-detect cancer cells that
have spread and are circulating in the body.
Chemotherapeutic drugs can be taken either orally
(by mouth) or intravenously, and may be given alone
or in conjunction with surgery, radiation or both.
When chemotherapy is used before surgery or
radiation, it is known as primary chemotherapy or
‘‘neoadjuvant chemotherapy.’’ An advantage of neoadjuvant chemotherapy is that since the cancer cells
have not been exposed to anti-cancer drugs, they are
especially vulnerable. It can therefore be used effectively to reduce the size of the tumor for surgery or
target it for radiation. However, the toxic effects of
neoadjuvant chemotherapy are severe. In addition, it
may make the body less tolerant to the side effects of
other treatments that follow such as radiation therapy.
The more common use of chemotherapy is adjuvant
therapy, which is given to enhance the effectiveness of
other treatments. For example, after surgery, adjuvant
chemotherapy is given to destroy any cancerous cells
that still remain in the body. In 2003, a new technique
was developed to streamline identification of drug compounds that are toxic to cancerous cells but not to
healthy cells. The technique identified nine dugs, one
of which had never before been identified for use in
cancer treatment. Researchers began looking into
developing the new drug for possible use.
GALE ENCYCLOPEDIA OF MEDICINE

Immunotherapy uses the body’s own immune system to destroy cancer cells. This form of treatment is
being intensively studied in clinical trials and is not yet
widely available to most cancer patients. The various
immunological agents being tested include substances
produced by the body (such as the interferons, interleukins, and growth factors), monoclonal antibodies,
and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer. Instead, they are designed
to treat people who already have the disease. Cancer
vaccines work by boosting the body’s immune system
and training the immune cells to specifically destroy
cancer cells.

cancers respectively. Many other specialists also may
be involved in the care of a cancer patient. For example,
radiologists specialize in the use of x rays, ultrasounds,
CT scans, MRI imaging and other techniques that are
used to diagnose cancer. Hematologists specialize in
disorders of the blood and are consulted in case of
blood cancers and bone marrow cancers. The samples
that are removed for biopsy are sent to a laboratory,
where a pathologist examines them to determine the
type of cancer and extent of the disease. Only some of
the specialists who are involved with cancer care have
been mentioned above. There are many other specialties, and virtually any type of medical or surgical specialist may become involved with care of the cancer
patient should it become necessary.

Hormone therapy
Hormone therapy is standard treatment for some
types of cancers that are hormone-dependent and
grow faster in the presence of particular hormones.
These include cancer of the prostate, breast, and
uterus. Hormone therapy involves blocking the production or action of these hormones. As a result the
growth of the tumor slows down and survival may be
extended for several months or years.
Bone marrow transplantation
The bone marrow is the tissue within the bone
cavities that contains blood-forming cells. Healthy
bone marrow tissue constantly replenishes the blood
supply and is essential to life. Sometimes, the amount
of drugs or radiation needed to destroy cancer cells
also destroys bone marrow. Replacing the bone marrow with healthy cells counteracts this adverse effect.
A bone marrow transplant is the removal of marrow
from one person and the transplant of the blood-forming cells either to the same person or to someone else.
Bone-marrow transplantation, while not a therapy in
itself, is often used to ‘‘rescue’’ patients, by allowing
those with cancer to undergo aggressive therapy.
Many different specialists generally work together
as a team to treat cancer patients. An oncologist is a
physician who specializes in cancer care. The oncologist
provides chemotherapy, hormone therapy, and any
other non-surgical treatment that does not involve
radiation. The oncologist often serves as the primary
physician and coordinates the patient’s treatment plan.
The radiation oncologist specializes in using
radiation to treat cancer, while the surgical oncologist performs the operations needed to diagnose or
treat cancer. Gynecologist-oncologists and pediatriconcologists, as their titles suggest, are physicians
involved with treating women’s and children’s
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
There are a multitude of alternative treatments
available to help the person with cancer. They can be
used in conjunction with, or separate from, surgery,
chemotherapy, and radiation therapy. Alternative
treatment of cancer is a complicated arena and a
trained health practitioner should be consulted.
Although the effectiveness of complementary
therapies such as acupuncture in alleviating cancer
pain has not been clinically proven, many cancer
patients find it safe and beneficial. Bodywork therapies such as massage and reflexology ease muscle tension and may alleviate side effects such as nausea and
vomiting. Homeopathy and herbal remedies used in
Chinese traditional herbal medicine also have been
shown to alleviate some of the side effects of radiation
and chemotherapy and are being recommended by
many doctors.
Certain foods including many vegetables, fruits,
and grains are believed to offer protection against
various cancers. However, isolation of the individual
constituent of vegetables and fruits that are anti-cancer
agents has proven difficult. In laboratory studies,
vitamins such as A, C and E, as well as compounds
such as isothiocyanates and dithiolthiones found in
broccoli, cauliflower, and cabbage, and beta-carotene
found in carrots have been shown to protect against
cancer. Studies have shown that eating a diet rich in
fiber as found in fruits and vegetables reduces the risk
of colon cancer. Exercise and a low fat diet help control weight and reduce the risk of endometrial, breast,
and colon cancer.
Certain drugs, which are currently being used for
treatment, could also be suitable for prevention. For
example, the drug tamoxifen (Nolvadex), which has
been very effective against breast cancer, is currently
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Cancer

Immunotherapy

Cancer

being tested by the National Cancer Institute for its
ability to prevent cancer. Similarly, retinoids derived
from vitamin A are being tested for their ability to
slow the progression or prevent head and neck cancers. Certain studies have suggested that cancer incidence is lower in areas where soil and foods are rich in
the mineral selenium. More trials are needed to
explain these intriguing connections.

KEY TERMS
Benign—Mild, nonmalignant. Recovery is favorable with treatment.
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic purposes.
Bone marrow—Spongy material that fills the inner
cavities of the bones. The progenitors of all the
blood cells are produced in this bone marrow.
Carcinogen—Any substance capable of causing
cancer by mutating the cell’s DNA.

Prognosis
‘‘Lifetime risk’’ is the term that cancer researchers
use to refer to the probability that an individual over
the course of a lifetime will develop cancer or die from
it. In the United States, men have a one in two lifetime
risk of developing cancer, and for women the risk is one
in three. Overall, African Americans are more likely
to develop cancer than whites. African Americans are
also 30% more likely to die of cancer than whites.

Chemotherapy—Treatment with certain anticancer
drugs.
Epithelium—The layer of cells covering the body’s
surface and lining the internal organs and various
glands.
Hormone therapy—Treatment of cancer by inhibiting the production of hormones such as testosterone and estrogen.

Most cancers are curable if detected and treated at
their early stages. A cancer patient’s prognosis is
affected by many factors, particularly the type of cancer the patient has, the stage of the cancer, the extent
to which it has metastasized and the aggressiveness of
the cancer. In addition, the patient’s age, general
health status and the effectiveness of the treatment
being pursued also are important factors.

Immunotherapy—Treatment of cancer by stimulating the body’s immune defense system.
Malignant—A general term for cells and the tumors
they form that can invade and destroy other tissues
and organs.
Metastasis—The spread of cancer from one part of
the body to another.

To help predict the future course and outcome of
the disease and the likelihood of recovery from
the disease, doctors often use statistics. The five-year
survival rates are the most common measures used.
The number refers to the proportion of people with
cancer who are expected to be alive, five years after
initial diagnosis, compared with a similar population
that is free of cancer. It is important to note that
while statistics can give some information about the
average survival experience of cancer patients in a
given population, it cannot be used to indicate individual prognosis, because no two patients are exactly
alike.

Prevention
According to nutritionists and epidemiologists
from leading universities in the United States, a person
can reduce the chances of getting cancer by following
some simple guidelines:

Radiation therapy—Treatment using high-energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Sore—An open wound, bruise or lesion on the skin.
Tumor—An abnormal growth resulting from a cell
that lost its normal growth control restraints and
started multiplying uncontrollably.
X rays—High–energy radiation used in high doses,
either to diagnose or treat disease.



decreasing or avoiding consumption of animal fats
and red meats



avoiding excessive amounts of alcohol



avoiding the midday sun (between 11 A.M. and
3 P.M.) when the sun’s rays are the strongest



eating plenty of vegetables and fruits



avoiding risky sexual practices



exercising vigorously for at least 20 minutes every day



avoiding known carcinogens in the environment or
work place



avoiding excessive weight gain



avoiding tobacco (even second hand smoke)

708

In addition, following the advice of physicians in
refraining from certain activities or drugs that are
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Simone, Joseph V. ‘‘Oncology: Introduction.’’ In Cecil
Textbook of Medicine, edited by Russel L. Cecil, et al.
Philadelphia: W.B. Saunders Company, 2000.
PERIODICALS

‘‘HRT Linked to Higher Breast Cancer Risk, Later
Diagnosis, Abnormal Mammograms.’’ Women’s
Health Weekly July 17, 2003: 2.
‘‘New Way to Stop Cancer Cell Growth Described.’’ Gene
Therapy Weekly December 12, 2002: 9.
‘‘Researchers Find New Way to Trigger Self-Destruction of
Certain Cancer Cells.’’ Biotech Week July 16, 2003: 285.
‘‘Technique Streamlines Search for Anticancer Drugs.’’
Cancer Weekly April 15, 2003: 62.
‘‘Virus Therapy Attacks Cancer Cells.’’ Cancer Weekly July
29, 2003: 50.
ORGANIZATIONS

American Cancer Society . 1599 Clifton Road, N.E. Atlanta,
GA 30329 (800) 227-2345. <http://www.cancer.org>.
Cancer Research Institute (National Headquarters). 681,
Fifth Avenue, New York, NY 10022 (800) 992-2623.
<http://www.cancerresearch.org>.
National Cancer Institute. 9000 Rockville Pike, Building 31,
room 10A16, Bethesda, Maryland, 20892 (800)4226237. <http://wwwicic.nci.nih.gov>.

Rosalyn Carson-DeWitt, MD
Teresa G. Odle

Cancer chemotherapy drugs see
Anticancer drugs

I Cancer therapy, definitive
Definition
Definitive cancer therapy is a treatment plan
designed to potentially cure cancer using one or a
GALE ENCYCLOPEDIA OF MEDICINE

combination of interventions including surgery, radiation, chemical agents, or biological therapies.

Purpose
The primary purpose of definitive care is to establish a cure and to destruct and remove all cancer cells
from the infected person.
Surgery is not only a diagnostic tool, but also used
for tumor removal. The surgeon usually identifies
potential candidates for tumor removal and repairs
intraoperatively (during the operation procedure).
Surgery can be curative for some stomach, genital/
urinary, thyroid, breast, skin, and central nervous
system cancers. The best chance for a surgical cure is
usually with the first operation. It is essential that the
cancer surgeon (oncologic surgeon) be experienced in
the specific procedure.
Radiation therapy is commonly administered to
approximately 50% of cancer patients during the
course of illness. It can be used as the sole method of
cure for tumors in the mouth and neighboring structures in the oral cavity, vagina, prostate, cervix, esophagus, Hodgkin’s disease, and certain types of cancer
in the spinal cord and brain. Research and clinical
trials have demonstrated that combination treatment
is more effective than radiation therapy alone.
Chemotherapy is curative for only a small percentage of cancers. It is most effective for choriocarcinoma, cancer of the testis, some types of lymphomas,
and cancer of skeletal muscles.
Biological therapies are a new and promising
direction for cancer cures. Usually when cancer cells
grow they manage to derive a blood supply that allows
passage of nutrients promoting continuation of
abnormal cancer growth. Research that focuses on
destroying these blood vessels is called angiogenesis.
Cutting off the blood supply has been shown to
destroy tumors, since this stops the flow of essential
nutrients required for cancer growth. Use of certain
growth factors also can stimulate self-destructive
pathways in cancer cells (apoptosis). Gene therapy is
directed toward inhibiting specific cellular signals that
promote cancer cell multiplication. The importance of
gene therapy in coming years will likely increase as
scientists made progress in 2002 and 2003 are mapping
the human genes (The Human Genome Project) and
identifying new ways to fight and perhaps cure cancer.
By using genetics, they hope to find new ways to
activate human defenses against tumor cells and
delay viral attacks on cells. Many trials were underway
in 2003 that showed great promise. One of these in
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Cancer therapy, definitive

proven as risk factors for certain cancers can help
lower one’s risk. For instance, while physicians have
long known a small increased risk for breast cancer
was linked to use of HRT, a landmark study released
in 2003 proved the risk was greater than thought. The
Women’s Health Initiative found that even relatively
short-term use of estrogen plus progestin is associated
with increased risk of breast cancer, diagnosis at a
more advanced stage of the disease, and a higher
number of abnormal mammograms. The longer a
woman used HRT, the more her risk increased.

Cancer therapy, definitive

2003 combined gene therapy and chemotherapy to
stop breast cancer and its spread (metastasis).

Precautions
Surgical resection requires an experienced surgeon, preoperative assessment, imaging studies, and
delicate operative technique. Care should be taken
during the procedure to avoid unnecessary tumor
manipulation, which can cause cancer cells to infiltrate
adjacent structures. If manipulation is excessive, cells
can enter nearby areas for future re-growth. Accurate
isolation of the tumor also can help avoid contamination of the surgical area. Early ligation of the blood
supply to the tumor is an essential component of a
surgical cure.
Radiation therapy requires extensive treatment
planning and imaging. Care must be taken to localize
the cancer field while attempting to spare destruction
of normal tissue. This requires image monitoring and
exact positioning during radiation treatment sessions.
Chemotherapy usually causes destruction of normal cells, and cancer cells can become immune to
chemical destruction. Side effects and patient tolerance issues typically are anticipated and dosages may
have to be specifically altered. Very few chemotherapeutic agents offer curative responses.
Biological therapies may cause patient toxicity
resulting in extensive side effects. This can occur
since the optimal dose may be exceedingly elevated
above patient tolerance.

Description
Surgery
Surgical removal of the tumor must be performed with care and accuracy. The surgeon must
avoid overmanipulation of the surgical field. Too
much movement within the area can cause cancer
cell displacement into surrounding tissue. If this
occurs and no further treatment is indicated, the
tumor may grow again. The surgeon also should perform an assessment concerning tissue removal
around the cancer site. Tissue around the site may
not by inspection seem cancerous, but adjacent structures may have cancer cells and surrounding tissue
removal is usually part of the operative procedure.
Pieces of tumor and the surrounding area are analyzed microscopically during the operation for cell
type. An adequate resection (removal of tissue) will
reveal normal cells in the specimens analyzed from
areas bordering the cancerous growth. Surgery also
710

can help to decrease the tumor bulk and, along with
other treatment measures, may provide a cure for
certain cancers. However, surgery is not always the
best answer. It generally works best on slow-growing
cancers.
Not only can surgery be curative for some cancers, but it is an essential diagnostic tool that must be
assessed intraoperatively since microscopic analysis
will guide the surgeon concerning tumor and surrounding tissue removal. These diagnostic procedures include an aspiration biopsy, which inserts a
needle to extract (aspirate) fluid contained inside a
cancerous growth; a needle biopsy uses a specialized
needle to obtain a core tissue specimen; an incision
biopsy removes a section from a large tumor; and an
excision biopsy removes the entire tumor. The surgeon also can take samples of neighboring lymph
nodes. Cancer in surrounding lymph nodes is an
important avenue for distant spread of cancer to
other areas. If microscopic analysis determines the
presence of cancer cells in lymph nodes, the surgeon
may decide to perform a more aggressive surgical
approach.
Radiation therapy
Similar to surgical intervention, radiation therapy
is a localized treatment. It involves the administration
of ionizing radiation to a solid tumor location. This
generates reactive oxygen molecules, causing the
destruction of DNA in local cells. There are three
commonly used radiation therapy beams: gamma
rays from a linear accelerator machine produce a
focused beam; orthovoltage rays are of less energy,
thus penetrate less and typically deliver higher doses
to superficial tissues (efficient for treating skin cancers); and megavoltage rays are high energy producing
beams that can penetrate deeply situated internal
organs, while sparing extensive skin damage. Two
common routes can deliver radiation. Brachytherapy
delivers radiation to a local area by placing radioactive
materials within close proximity to the cancerous site.
Teletherapy delivers radiation to a specific area using
an external beam machine.
Chemotherapy
Curative chemotherapy usually requires multiple
administrations of the chemical agent. Chemotherapy
or systemic therapy is administered in the blood and
circulates through the entire body. The choice of
chemotherapeutic agents depends on the specific type
of cancer. Chemotherapy is more commonly used for
metastatic (malignant cancer which has spread to
GALE ENCYCLOPEDIA OF MEDICINE

Biologic therapy
Biologic therapies primarily function to alter the
patient’s response to cancer. These treatments are
mostly investigations and there are numerous
research protocols studying the effects of biologic
treatments. These protocols usually have strict
admission criteria that may exclude potential candidates who can benefit from treatment. These treatments tend to stimulate specific immune cells or
immune chemicals to destroy cancer cells.

KEY TERMS
Bone marrow suppression—A decrease in cells
responsible for providing immunity, carrying
oxygen, and those responsible for normal blood
clotting.
DNA—The molecule responsible for cell
multiplication.
Titrate—To analyze the best end point (for dose)
for a medication.

microsurgery of blood vessels) can restore new tissues
to a previous surgery site.

Preparation
For all treatment modalities imaging studies,
biopsy, and constant blood analysis is essential before,
during, and after treatments. Surgical candidates
should undergo extensive pre-operative evaluation
with imaging studies, blood chemistry analysis, stabilized health status, and readiness of staff for any
potential complications and cell biopsy analysis.
Patients with other pre-existing chronic disease may
require intensive post-operative monitoring.
For radiotherapy, the patient undergoes extensive
imaging studies. Additional planning strategies
include beam localization to spare normal tissues,
calibration of fractionated doses, and specific positioning during treatment sessions.
Patients who receive curative chemotherapy
should be informed of possible side effects associated
with the chemotherapeutic agent. Patients should also
be informed of temporary lifestyle changes and medications that may offer some symptomatic relief.
Patients undergoing biologic therapies are usually
advised of potential side effects, treatment cycles and
specific tests for monitoring progress according to the
specific research protocol.

Aftercare
Patients will typically be evaluated by imaging
studies, blood analysis, physical examination, and
health improvement. These follow-up visits usually
occur at specific time intervals during the course of
treatment. Surgical patients may require closer observation during the initial post-operative period to avoid
potential complications. Reconstructive surgery can be
considered to improve appearance and restore function. Certain surgical procedures (such as flaps and
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Surgical risks
Surgical therapy can be both disfiguring and disabling. Many normal tissues can be adversely affected
by radiation therapy. Side effects that commonly
occur shortly after a treatment cycle include nausea,
vomiting, fatigue, loss of appetite, and bone marrow
suppression (a decrease in the cells that provide
defense against infections and those that carry oxygen
to cells).
Radiation risks
Radiation therapy also can cause difficulty swallowing, oral gum disease, and dry mouth. Additionally,
radiation therapy can cause damage to local structures
within the irradiated field.
Chemotherapy risks
Chemotherapy commonly causes bone marrow
suppression. Additionally, cells called platelets—
important for normal blood clotting—may be significantly lowered, causing patients to bleed. This may be
problematic enough to limit the treatment course.
Bone marrow suppression can increase susceptibility
to infection and also cause infertility. Patients commonly have bouts of nausea and vomiting shortly after
a treatment session. Rapidly multiplying normal cells
also are affected such as skin cells (causing blistering
and ulceration) and hair cells causing loss of hair, a
condition called alopecia).
Biologic therapy risks
Biologic therapies can cause patients to develop
suppression of cells that help the body fight against
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Cancer therapy, definitive

other areas beyond the primary site of cancer growth)
disease, since very few cancers are cured by systemic
therapy.

Cancer therapy, palliative

infection. Administration of certain chemicals that
have anticancer effects can cause heart damage.
Injection of killer immune cells (lymphokine-activated
killer cells) may cause bone marrow suppression, and
the host may reject the newly introduced cells.
Resources
BOOKS

Abeloff, Martin D., et al. Clinical Oncology. 2nd ed.
Churchill Livingstone, Inc, 2000.
Goroll, Allan H., et al, editors. Primary Care Medicine.
4th ed. Lippincott, Williams & Wilkins, 2000.
PERIODICALS

‘‘Gene Therapy and Chemotherapy Combine to Stop Breast
Cancer and its Metastasis.’’ Gene Therapy Weekly
October 30, 2003: 2.
‘‘Surgery Not Always Best Cancer Treatment Option:
Weigh Advantages and Disadvantages Before
Decision.’’ Patient Education Management July
2003: 78.
Wachter, Kerri. ‘‘Gene Therapy Holds Promise for Curing
Cancer: Four Preliminary Trials.’’ Internal Medicine
News September 15, 2003: 22.
OTHER

American Cancer Society. <http://www.cancer.org>.
National Cancer Institute. <http://cnetdb.nci.nih.gov/
cancerlit.shtml.>.

Laith Farid Gulli, M.D.
Nicole Mallory, M.S.
Teresa G. Odle

treatment planning process. Therapeutic planning
usually involves careful coordination with the treatment team. The approach to palliative care also
involves easing psychosocial problems and an
emphasis on the patient’s family.
Surgery can be utilized for palliation after careful
evaluation and planning. The use of surgery in these
cases may reduce the tumor bulk and help improve
the quality of life by relieving pain, alleviating
obstruction, or controlling bleeding. Radiation therapy for terminal cancer patients can also alleviate
pain, bleeding, and obstruction of neighboring
areas. New research in 2003 showed that using a
combination of radiation therapy bisphosphanates
helped offer palliative relief to patients with metastatic bone disease (metastatic disease is cancer that
has spread beyond the original site or organ to other
areas of the body). Chemotherapy may be helpful
to reduce tumor size and provide some reduction
to metastatic disease. Long-term chemotherapy
patients develop drug resistance, a situation that renders chemotherapeutic treatments ineffective. If this
occurs, patients usually are given a second line medication or, if admission criteria are met, they may
participate in an experimental research protocol.
Palliative treatments and terminal cancer in combination can cause many symptoms that can become
problematic. These symptoms commonly include
pain, nausea, vomiting, difficulty in breathing, constipation, dehydration, agitation, and delirium. The palliative treatment-planning goal focuses on reducing
these symptoms.

Precautions

I Cancer therapy, palliative
Definition
Palliative cancer therapy is treatment specifically
directed to help improve the symptoms associated
with terminal cancer.

Purpose
Palliative care is directed to improving symptoms
associated with incurable cancer. Care can include
surgery, radiation therapy, chemotherapy, symptomatic treatments resulting from cancer, and side
effects of treatment. The primary objective of palliative care is to improve the quality of the remainder of
a patient’s life. Treatment usually involves a combination of modalities (multimodality approach) and
numerous specialists typically are involved in the
712

Surgery for tumor removal, biopsy, or size reduction is associated with postoperative pain and local
nerve damage, which may be both severe and difficult
to alleviate. Chemotherapy and radiation therapy also
can produce nerve damage and severe pain.
Additionally, patients with malignant cancer are susceptible to infections like herpes, pneumonia, urinary
tract infections, and wound abscess, all of which can
cause severe pain. Pain associated with cancer and/or
treatments can significantly impair the patient’s abilities to perform daily tasks and hence impair quality of
life. These complications may negatively impact the
patient’s psychological well-being.

Description
Pain is one of the common symptoms associated
with cancer. Approximately 75% of terminal cancer
patients have pain. Pain is a subjective symptom
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
Patients typically are informed that their diagnosis is terminal and treatments are directed to improve
quality of life an ease suffering for the remaining time.
Treatment also is aimed to minimize emotional suffering associated with pain.
A careful history is necessary to assess duration,
severity, and location of pain. A physical examination
may verify the presence of pain. Imaging analysis may
further confirm the presence of potential causes
of pain. The World Health Organization (WHO)
recommends an analgesic ladder. This treatment
approach provides medication selections based on
previous analgesic use and severity of pain. The ladder
starts with the use of non-opioid (non-morphine)
drugs such as aspirin, acetaminophen, or non-steroidal
anti-inflammatory medications (NSAIDs) for control
of mild pain. Chronic pain must be treated with constant and consistently administered medication(s).
The ‘‘take as needed’’ approach is not advised.
Supplemental doses may be recommended in addition
to the standard dose for circumstances that may worsen pain. Opioids (i.e., morphine and codeine) are the
medications of choice for moderate to severe pain.
Doses are adjusted to produce maximum pain relief
while minimizing side effects. These medications are
conveniently administered orally. Administering steroids can help reduce nausea and vomiting. Delirium
and anxiety may be improved by psychoactive
medications.

Aftercare
Care for palliation is continuous and consistent
for the remainder of life. Patients who have less than
six months of life remaining may choose a hospice to
stop treatment and control pain. Nutritional care is
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Opioids—Narcotic pain killing medications.
World Health Organization (WHO)— An international organization concerned with world health
and welfare.

an important part of palliative care, since many
patients suffer malnourishing effects of radiation
and chemotherapy and those who can maintain pleasure from food should. A proper diet can offset
effects of the many medications patients on palliative
care may receive.

Risks
Patients taking opioids for pain relief can develop
tolerance and dependence. Tolerance develops when a
patient requires increasing amounts of medication to
produce pain reduction. Dependence shows characteristic withdrawal symptoms if medications are abruptly
stopped. These symptoms can be avoided by tapering
down doses in the event that these medications should
be stopped.
Resources
BOOKS

Abeloff, Martin D., et al. Clinical Oncology. 2nd ed.
Churchill Livingstone, Inc, 2000.
Goroll, Allan H., et al., editors. Primary Care Medicine.
4th ed. Lippincott, Williams & Wilkins. 2000.
Washington Manual of Medical Therapeutics. 30th ed.
Washington University School of Medicine,
Department of Medicine, 2001.
PERIODICALS

‘‘Bisphosphanates, Radiation Therapy Can be Used for
Metastatic Bone Disease.’’ Cancer Weekly October 28,
2003: 112.
Cimino, James E. ‘‘The Role of Nutrition in Hospice and
Palliative Care of the Cancer Patient.’’ Topics in Clinical
Nutrition July–September 2003: 154–158.
Mercadante, S., F. Fulfaro, and A. Casuccio. ‘‘The Impact
of Home Palliative Care on Symptoms in Advanced
Cancer Patients.’’ Support Care Cancer July 2000.
ORGANIZATIONS

American Cancer Society. <http://www.cancer.org>.
American Pain Society. <http://www.ampiansoc.org>.
National Cancer Institute. <http://cnetdb.nci.nih.gov/
cancerlit.shtml>.
713

Cancer therapy, palliative

and thus it cannot be measured using technological
approaches. Pain can be assessed using numeric scales
(from one to 10, one is rated as no pain while 10 is
severe) or rating specific facial expressions associated
with various levels of pain. The majority of cancer
patients experience pain as a result of tumor mass
that compresses neighboring nerves, bone, or soft tissues, or from direct nerve injury (neuropathic pain).
Pain can occur from affected nerves in the ribs, muscles, and internal structures such as the abdomen
(cramping type pain associated with obstruction).
Many patients also experience various types of pain
as a direct result of follow-up tests, treatments (surgery, radiation, and chemo–therapy) and diagnostic
procedures (i.e., biopsy).

Cancer therapy, supportive

OTHER

‘‘Improving Palliative Care for Cancer.’’ Report
and Booklet. Institute of Medicine, 2001. <http://
www.nap.edu/catalog/10790/html>.

Laith Farid Gulli, M.D.
Nicole Mallory, M.S.
Teresa G. Odle

I Cancer therapy, supportive
Definition
Supportive cancer therapy is the use of medicines
to counteract unwanted effects of cancer treatment.

Purpose
Along with their beneficial effects, many cancer
treatments produce uncomfortable and sometimes
harmful side effects. For example, cancer drugs may
cause nausea or vomiting. They also may destroy red or
white blood cells, resulting in a low blood count.
Fortunately, many of these side effects can be relieved
with other medicines.

Description
Different kinds of drugs are used for different
purposes in supportive cancer therapy. To relieve nausea and vomiting, a physician may prescribe dolasetron
(Anzemet), granisetron (Kytril) or ondansetron
(Zofran). Drugs called colony stimulating factors are
used to help the bone marrow make new white blood
cells to replace those destroyed by cancer treatment.
Examples of colony stimulating factors are filgrastim
(Neupogen) and sargramostim (Leukine). Another
type of drug, epoetin (Epogen, Procrit), stimulates
the bone marrow to make new red blood cells and
help patients overcome anemia. It is a synthetically
made version of human erythropoietin that is made
naturally in the body and has the same effect on bone
marrow.
Some physicians who treat cancer recommend
that their patients use marijuana to relieve nausea
and vomiting. This practice is controversial for several reasons. Using marijuana, even for medicinal
purposes, is illegal in most states. Also, most of the
evidence that marijuana effectively relieves nausea
and vomiting comes from reports of people who
have used it, not from carefully designed scientific
714

studies called clinical trials. An oral medication
that contains one of the active ingredients of marijuana is available with a physician’s prescription and
sometimes is used to treat nausea and vomiting in
patients undergoing cancer treatment. However, the
drug, dronabinol (Marinol), takes longer to work
than smoked marijuana and may be difficult for
patients with nausea and vomiting to swallow and
keep down.
In 1997, the National Institutes of Health issued a
report calling for more research into medical uses of
marijuana. The panel of experts who wrote the report
also recommended that researchers investigate other
ways of getting the active ingredients of marijuana
into the body, such as nasal sprays, skin patches and
inhalers. In 2000, the American Cancer Society funded
research into a skin patch. A 2003 report said
that a University of Kentucky researcher had applied
for a patent for the patch which used synthetic
cannabinoids.
Patients who want to use marijuana to relieve side
effects of cancer treatment should talk to their physicians and should carefully consider the benefits and
risks, both medical and legal.

Recommended dosage
The recommended dosage depends on the type
of supportive cancer therapy. The physician who
prescribed the drug or the pharmacist who filled the
prescription can recommend the correct dosage.

Precautions
Dolasetron, granisetron and ondansetron
If severe nausea and vomiting occur after taking
this medicine, patients should check with a physician.
The use of ondansetron after abdominal surgery
may cover up symptoms of stomach problems.
People with liver disease may be more likely to
have side effects from ondansetron.
Colony stimulating factors
Certain cancer drugs reduce the body’s ability to
fight infections. Although colony stimulating factors
help restore the body’s natural defenses, the process
takes time. Getting prompt treatment for infections is
important, even while taking this medicine. A patient
should call the physician at the first sign of illness or
infection, such as a sore throat, fever or chills.
GALE ENCYCLOPEDIA OF MEDICINE

People with certain medical conditions may have
problems if they take colony stimulating factors. In
people who have kidney disease, liver disease, or conditions caused by inflammation or immune system
problems, colony stimulating factors may make these
problems worse. People with heart disease may be
more likely to have side effects such as water retention
and heart rhythm problems when they take these
drugs. And people with lung disease may be more
likely to have shortness of breath. Anyone who has
any of these medical conditions should check with
his or her physician before using colony stimulating
factors.
Epoetin
This medicine may cause seizures (convulsions),
especially in people with a history of seizures. Anyone
who takes these drugs should not drive, use machines
or do anything else that might be dangerous if they
have had a seizure.
Epoetin helps the body make new red blood cells,
but it cannot do its job unless there is plenty of iron in
the body. The physician may recommend taking iron
supplements or certain vitamins that help get iron into
the body. Following the physician’s orders to make
sure the body has enough iron for this medicine makes
it work. Iron supplements should not be taken unless
they are prescribed by a physician.
In studies of laboratory animals, epoetin taken
during pregnancy caused birth defects, including
damage to the bones and spine. However, the drug
has not been reported to cause problems in human
babies whose mothers take it. Women who are pregnant or who may become pregnant should check
with their physicians for the most up-to-date information on the safety of taking this medicine during
pregnancy.
People with certain medical conditions may have
problems if they take this medicine. For example, the
chance of side effects may be greater in people with
high blood pressure, heart or blood vessel disease or a
history of blood clots. Epoetin may not work properly
in people who have bone problems or sickle cell
anemia.
Research continues on the benefits of epoetin as a
supportive cancer therapy. One 2003 report said new
research showed doubt as to its effectiveness in treating anemia, while other reports confirmed it worked
GALE ENCYCLOPEDIA OF MEDICINE

well. In mid-2003, a new large clinical trial (CREATE)
was beginning in England to help determine epoetin’s
effectiveness.
Dronabinol
This medicine contains sesame oil and one of the
active ingredients of marijuana. Anyone who has had
allergic or unusual reactions to sesame oil or marijuana products should let his or her physician know
before taking dronabinol.
Because dronabinol works on the central nervous
system, it may add to the effects of alcohol and other
drugs that slow down the central nervous system.
Examples of these drugs are antihistamines, cold medicine, allergy medicine, sleep aids, medicine for seizures, tranquilizers, some pain relievers, and muscle
relaxants. Dronabinol also may add to the effects of
anesthetics, including those used for dental procedures. Anyone taking dronabinol should not drink
alcohol and should check with his or her physician
before taking any of the drugs listed above.
This drug makes some people feel drowsy, dizzy,
lightheaded or ‘‘high,’’ with a sense of well-being.
Because of these possible reactions, anyone who
takes dronabinol should not drive, use machines or
do anything else that might be dangerous until they
have found out how the drug affects them. The dizziness and lightheadedness are especially likely when
getting up after sitting or lying down. Getting up
gradually and holding onto something for support
should lessen the problem.
In laboratory studies, giving high doses of dronabinol to pregnant animals increased the risk of the
unborn baby’s death. The medicine’s effects on pregnant women have not been studied. Women who are
pregnant or who may become pregnant should check
with their physicians before taking this medicine.
Dronabinol passes into breast milk and may
affect nursing babies whose mothers take the medicine. Women who are breastfeeding their babies
should check with their physicians before using
dronabinol.
Because of its possible mind-altering effects, dronabinol should be used with care in children and
older people. Both children and older people should
be watched carefully when they are taking this
medicine.
Using dronabinol may worsen some medical conditions, including high blood pressure, heart disease,
bipolar disorder and schizophrenia.
715

Cancer therapy, supportive

Seeing a physician regularly while taking this
medicine is important. This will give the physician a
chance to make sure the medicine is working and to
check for unwanted side effects.

Cancer therapy, supportive

General precautions for all types of supportive
cancer therapy
Anyone who previously has had unusual reactions
to drugs used in supportive cancer therapy should
let his or her physician know before taking the drugs
again. The physician should also be told about
any allergies to foods, dyes, preservatives, or other
substances.

Certain side effects should be brought to a physician’s attention as soon as possible. These include
headache, vision problems, increased blood pressure,
fast heartbeat, weight gain, and swelling of the face,
fingers, lower legs, ankles or feet.
Anyone who has chest pain or seizures after
taking epoetin should check with a physician
immediately.

Side effects
Dolasetron, granisetron and ondansetron
The most common minor side effects are headache,
dizziness or lightheadedness, drowsiness, dry mouth,
diarrhea, constipation, abdominal pain or stomach
cramps and unusual tiredness or weakness. These problems usually do not require medical treatment.
A physician should be notified as soon as possible
if fever occurs after taking granisetron.
If any of these symptoms occur after taking
ondansetron, the patient should check with a physician immediately:

Dronabinol
Side effects such as dizziness, drowsiness, confusion and clumsiness or unsteadiness usually do not
need medical attention unless they are long-lasting or
they interfere with normal activities.
Other side effects or signs of overdose should have
immediate medical attention. These include:


fast or pounding heartbeat



constipation



trouble urinating



red eyes



breathing problems or wheezing



slurred speech



chest pain or tightness in chest





skin rash, hives or itching

mood changes, including depression, nervousness or
anxiety



confusion



forgetfulness



changes in sight, smell, taste, touch or hearing



a sense that time is speeding up or slowing down



hallucinations

Colony stimulating factors
As this medicine starts to work, it may cause mild
pain in the lower back or hips. This is nothing to worry
about, and it will usually go away within a few days. If
the pain is too uncomfortable, the physician may prescribe a painkiller. A physician needs to know if the
painkiller does not help.
Other possible side effects include headache, joint
or muscle pain, and skin rash or itching. These side
effects usually go away as the body adjusts to the
medicine and do not need medical treatment. If they
continue or interfere with normal activities, a physician should be notified.
Epoetin
This medicine may cause flu-like symptoms, such
as muscle aches, bone pain, fever, chills, shivering, and
sweating, within a few hours after it is taken. These
symptoms usually go away within 12 hours. If they do
not, or if they are troubling, a physician should be
told. Other possible side effects that do not need medical attention are diarrhea, nausea or vomiting, and
tiredness or weakness.
716

General advice on side effects for all types
of supportive cancer therapy
Other side effects are possible with any type of
supportive cancer therapy. Anyone who has unusual
symptoms during or after treatment with these drugs
should get in touch with his or her physician.

Interactions
Anyone who has supportive cancer therapy
should let the physician know all other medicines he
or she is taking. Some combinations of drugs may
interact, which may increase or decrease the effects
of one or both drugs or may increase the risk of side
effects. Patients should ask their physician if the possible interactions can interfere with drug therapy or
cause harmful effects.
GALE ENCYCLOPEDIA OF MEDICINE

Bipolar disorder—A severe mental illness in which
a person has extreme mood swings, ranging from a
highly excited state — sometimes with a false sense
of well-being — to depression
Bone marrow—Soft tissue that fills the hollow
centers of bones. Blood cells and platelets (diskshaped bodies in the blood that are important in
clotting) are produced in the bone marrow.
Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Immune system—The body’s natural defenses
against disease and infection.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Schizophrenia—A severe mental disorder in
which people lose touch with reality and may
have illogical thoughts, delusions, hallucinations,
behavioral problems and other disturbances.
Sickle cell anemia—An inherited disorder in
which red blood cells contain an abnormal form
of hemoglobin, a protein that carries oxygen.
The abnormal form of hemoglobin causes the red
cells to become sickle- or crescent-shaped. The
misshapen cells may clog blood vessels, preventing
oxygen from reaching tissues and leading to
pain, blood clots and other problems. Sickle cell
anemia is most common in people of African descent and in people from Italy, Greece, India, and
the Middle East.

Resources
PERIODICALS

‘‘CREATE Trial Providing Valuable Information on
Epoetin Treatment for Anemia.’’ Hematology Week
August 25, 2003: 10.
‘‘Doubts Over Epoetin in Cancer.’’ SCRIP World
Pharmaceutical News October 24, 2003: 24.
‘‘Researcher Working on Medical Patch to Deliver
Marijuana–like Drug.’’ Cancer Weekly September 9,
2003: 126.

Nancy Ross-Flanigan
Teresa G. Odle

Candida albicans infection see Candidiasis
GALE ENCYCLOPEDIA OF MEDICINE

Candidiasis

KEY TERMS

I Candidiasis
Definition
Candidiasis is an infection caused by a species of
the yeast Candida, usually Candida albicans. This is a
common cause of vaginal infections in women. Also,
Candida may cause mouth infections in people with
reduced immune function, or in patients taking certain antibiotics. Candida can be found in virtually all
normal people but causes problems in only a fraction.
In recent years, however, several serious categories of
candidiasis have become more common, due to overuse of antibiotics, the rise of AIDS, the increase in
organ transplantations, and the use of invasive
devices (catheters, artificial joints and valves)—all
of which increase a patient’s susceptibility to
infection.

Description
Vaginal candidiasis
Over one million women in the United States
develop vaginal yeast infections each year. It is not
life-threatening, but it can be uncomfortable and
frustrating.
Oral candidiasis
This disorder, also known as thrush, causes white,
curd-like patches in the mouth or throat.
Deep organ candidiasis
Also known as invasive candidiasis, deep organ
candidiasis is a serious systemic infection that can
affect the esophagus, heart, blood, liver, spleen, kidneys, eyes, and skin. Like vaginal and oral candidiasis,
it is an opportunistic disease that strikes when a person’s resistance is lowered, often due to another illness. There are many diagnostic categories of
deep organ candidiasis, depending on the tissues
involved.

Causes and symptoms
Vaginal candidiasis
Most women with vaginal candidiasis experience
severe vaginal itching. They also have a discharge that
often looks like cottage cheese and has a sweet or
bread-like odor. The vulva and vagina can be red,
swollen, and painful. Sexual intercourse can also be
painful.
717

Candidiasis

RACHEL FULLER BROWN
(1898–1980)
Rachel Fuller Brown was born on November 23,
1898 in Springfield, Massachusetts. Brown was the
oldest of two children born to Annie (Fuller) and
George Hamilton Brown. In 1912, her father left their
family in Missouri and her mother moved the family
back to Springfield. Brown double majored in history
and chemistry at Mount Holyoke, receiving her A.B.
degree in 1920. She also earned her M.A. degree from
the University of Chicago. Brown began her doctoral
studies at the University, but she experienced financial
difficulties and took a job before she received her
Ph.D. She worked at the Division of Laboratories and
Research of the New York State Department of Health
as an assistant chemist for seven years and finally
returned to Chicago and completed her Ph.D.
In 1948, Brown and Elizabeth Hazen began
researching fungal infections found in humans due to
antibiotic treatments and diseases. Some of the antibiotics they discovered did indeed kill the fungus; however, they also killed the test mice. Finally, Hazen
located a microorganism on a farm in Virginia, and
Brown’s tests indicated that the microorganism produced
two antibiotics, one of which proved effective for treating fungus and candidiasis in humans. Brown purified
the antibiotic which was patented under the name nystatin. In 1954, the antibiotic became available in pill
form. Brown and Hazen continued their research and
discovered two other antibiotics. Brown received
numerous awards individually and with her research
partner, Elizabeth Hazen. Rachel Brown passed away
on January 14, 1980.

Oral candidiasis
Whitish patches can appear on the tongue, inside
of the cheeks, or the palate. Oral candidiasis typically
occurs in people with abnormal immune systems.
These can include people undergoing chemotherapy
for cancer, people taking immunosuppressive drugs
to protect transplanted organs, or people with HIV
infection.
Deep organ candidiasis
Anything that weakens the body’s natural barrier
against colonizing organisms—including stomach surgery, burns, nasogastric tubes, and catheters—can predispose a person for deep organ candidiasis. Rising
numbers of AIDS patients, organ transplant recipients, and other individuals whose immune systems
718

This patient’s tongue is infected with candidiasis.
(Photograph by Edward H. Gill, Custom Medical Stock Photo.
Reproduced by permission.)

are compromised help account for the dramatic
increase in deep organ candidiasis in recent years.
Patients with granulocytopenia (deficiency of white
blood cells) are particularly at risk for deep organ
candidiasis.

Diagnosis
Often clinical appearance gives a strong suggestion about the diagnosis. Generally, a clinician will
take a sample of the vaginal discharge or swab an
area of oral plaque, and then inspect this material
under a microscope. Under the microscope, it is possible to see characteristic forms of yeasts at various
stages in the lifecycle.
Fungal blood cultures should be taken for
patients suspected of having deep organ candidiasis.
Tissue biopsy may be needed for a definitive
diagnosis.

Treatment
Vaginal candidiasis
In most cases, vaginal candidiasis can be treated
successfully with a variety of over-the-counter antifungal creams or suppositories. These include
Monistat, Gyne-Lotrimin, and Mycelex. However,
infections often recur. If a women has frequent
GALE ENCYCLOPEDIA OF MEDICINE

Biopsy—The removal and examination of tissue
from a live body.
Colonize—To become established in a host.
Granulocytopenia—A condition characterized by
a deficiency of white blood cells.
Nasogastric—Tube inserted through the nasal passages into the stomach.

A transmission electron microscopy (TEM) of Candida
albicans. (Custom Medical Stock Photo. Reproduced by
permission.)

recurrences, she should consult her doctor about prescription drugs such as Vagistat-1, Diflucan, and
others.

Opportunistic—Infection caused by microorganisms that are usually harmless, but which can
cause disease when a host’s resistance is lowered.
Systemic—Afflicting an entire body system or the
body in general.

Prognosis
Vaginal candidiasis

Oral candidiasis
This is usually treated with prescription lozenges
or mouthwashes. Some of the most-used prescriptions
are nystatin mouthwashes (Nilstat or Nitrostat) and
clotrimazole lozenges.
Deep organ candidiasis
The recent increase in deep organ candidiasis has
led to the creation of treatment guidelines, including,
but not limited to, the following: Catheters should be
removed from patients in whom these devices are still
present. Antifungal chemotherapy should be started
to prevent the spread of the disease. Drugs should be
prescribed based on a patient’s specific history and
defense status.

Alternative treatment
Home remedies for vaginal candidiasis include
vinegar douches or insertion of a paste made from
Lactobacillus acidophilus powder into the vagina. In
theory, these remedies will make the vagina more
acidic and therefore less hospitable to the growth of
Candida. Fresh garlic (Allium sativum) is believed to
have antifungal action, so incorporating it into the diet
or inserting a gauze-wrapped, peeled garlic clove into
the vagina may be helpful. The insert should be changed twice daily. Some women report success with these
remedies; they should try a conventional treatment if
an alternative remedy isn’t effective.
GALE ENCYCLOPEDIA OF MEDICINE

Although most cases of vaginal candidiasis are
cured reliably, these infections can recur. To limit
recurrences, women may need to take a prescription
anti-fungal drug such as terconazole (sold as Terazol)
or take other anti-fungal drugs on a preventive basis.
Oral candidiasis
These infections can also recur, sometimes
because the infecting Candida develops resistance to
one drug. Therefore, a physician may need to prescribe
a different drug.
Deep organ candidiasis
The prognosis depends on the category of disease
as well as on the condition of the patient when the
infection strikes. Patients who are already suffering
from a serious underlying disease are more susceptible
to deep organ candidiasis that speads throughout
the body.

Prevention
Because Candida is part of the normal group of
microorganisms that co-exist with all people, it is
impossible to avoid contact with it. Good vaginal
hygiene and good oral hygiene might reduce problems,
but they are not guarantees against candidiasis.
Because hospital-acquired (nosocomial) deep
organ candidiasis is on the rise, people need to be
made aware of it. Patients should be sure that catheters
719

Candidiasis

KEY TERMS

Canker sores

are properly maintained and used for the shortest possible time length. The frequency, length, and scope of
courses of antibiotic treatment should also be cut back.
Resources
PERIODICALS

Greenspan, Deborah, and John S. Greenspan.
‘‘HIV-Related Oral Disease.’’ The Lancet 348
(September 14, 1996): 729-734.

Richard H. Lampert

KEY TERMS
Inflammation—A local reaction to tissue injury or
damage, usually characterized by pain, swelling,
and redness.
Sore—A wound, lesion, or ulcer on the skin.
Ulcer—A site of damage to the skin or mucous
membrane that is characterized by the formation
of pus, death of tissue, and is frequently accompanied by an inflammatory reaction.

Candidosis see Candidiasis

I Canker sores
Definition
Canker sores are small sores or ulcers that appear
inside the mouth. They are painful, self-healing, and
can recur.

Description
Canker sores occur on the inside of the mouth,
usually on the inside of the lips, cheeks, and/or soft
palate. They can also occur on the tongue and in the
throat. Often, several canker sores will appear at
the same time and may be grouped in clusters.
Canker sores appear as a whitish, round area with a
red border. The sores are painful and sensitive to
touch. The average canker sore is about one-quarter
inch in size, although they can occasionally be larger.
Canker sores are not infectious.
Approximately 20% of the U.S. population is
affected with recurring canker sores, and more
women than men get them. Women are more likely
to have canker sores during their premenstrual period.
Canker sores are sometimes confused with cold
sores. Cold sores are caused by herpes simplex virus.
This disease, also known as oral herpes or fever blisters, can occur anywhere on the body. Most commonly, herpes infection occurs on the outside of the
lips and the gums, and much less frequently on the
inside the mouth. Cold sores are infectious.

Causes and symptoms
The exact cause of canker sores is uncertain, however, they seem to be related to a localized immune
reaction. Other proposed causes for this disease are
720

trauma to the affected areas from toothbrush scrapes,
stress, hormones, and food allergies. Canker sores tend
to appear in response to stress. The initial symptom is
a tingling or mildly painful itching sensation in the area
where the sore will appear. After one to several days, a
small red swelling appears. The sore is round, and is a
whitish color with a grayish colored center. Usually,
there is a red ring of inflammation surrounding the
sore. The main symptom is pain. Canker sores can be
very painful, especially if they are touched repeatedly,
e.g., by the tongue. They last for one to two weeks.

Diagnosis
Canker sores are diagnosed by observation of the
blister. A distinction between canker sores and cold
sores must be made because cold sores are infectious
and the herpes infection can be transmitted to other
people. The two sores can usually be distinguished
visually and there are specific diagnostic tests for
herpes infection.

Treatment
Since canker sores heal by themselves, treatment is
not usually necessary. Pain relief remedies, such as topical anesthetics, may be used to reduce the pain of the
sores. The use of corticosteroid ointments sometimes
speeds healing. Avoidance of spicy or acidic foods can
help reduce the pain associated with canker sores.

Alternative treatment
Alternative therapies for canker sores are aimed at
healing existing sores and preventing their recurrence.
Several herbal remedies, including calendula (Calendula
officinalis), myrrh (Commiphora molmol ), and goldenseal (Hydrastis canadensis), may be helpful in the treatment of existing sores. Compresses soaked in teas made
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
There is no cure for canker sores. They do not get
larger or occur more frequently with age.
Resources

glucose (the form in which sugar circulates in the
blood), fructose (found in fruit and honey), and galactose (produced by the digestion of milk). These simple
sugars are important because they can be absorbed by
the small intestine. Two simple sugars linked together
make a disaccharide. The disaccharide sugars present
in the diet are maltose (a product of the digestion of
starch), sucrose (table sugar), and lactose (the sugar in
milk). These disaccharides must be broken down by
enzymes into two simple sugars so that they can be
absorbed by the intestine. Polysaccharides are much
more complex carbohydrates made up of many simple
sugars, the most important of which are glycogen,
which is stored in the liver, and starch.
Digestion of sugars

BOOKS

Larsen, D. E., editor. Mayo Clinic Family Health Book.
New York: William Morrow, 1996.

John T. Lohr, PhD

Captopril see Angiotensin-converting
enzyme inhibitors
Carbamazepine see Anticonvulsant drugs
Carbidopa see Antiparkinson drugs

I Carbohydrate intolerance
Definition
Carbohydrate intolerance is the inability of the
body to completely process the nutrient carbohydrate
(a classification that includes sugars and starches) into
a source of energy for the body, usually because of the
deficiency of an enzyme needed for digestion. Lactose
intolerance, the inability to digest the sugar found in
milk, is widespread and affects up to 70% of the
world’s adult population.

Description
Carbohydrates are the primary source of energy
and, along with fats and proteins, one of the three
major nutrients in the human diet. Carbohydrates
are classified according to their structure based on
the number of basic sugar, or saccharide units they
contain.
A monosaccharide is the simplest carbohydrate
and called a simple sugar. Simple sugars include
GALE ENCYCLOPEDIA OF MEDICINE

Digestion of food begins in the mouth, moves on
to the stomach, and then into the small intestine.
Along the way, specific enzymes are needed to process
different types of sugars. An enzyme is a substance
that acts as a catalyst to produce chemical changes
without being changed itself. The enzymes lactase,
maltase, and isomaltase (or sucrase) are needed to
break down the disaccharides; when one or more is
inadequate, the result is carbohydrate intolerance.
Types of intolerance
Carbohydrate intolerance can be primary or secondary. Primary deficiency is caused by an enzyme
defect present at birth or developed over time.
The most common is lactose intolerance. Secondary
deficiencies are caused by a disease or disorder of the
intestinal tract, and disappear when the disease is
treated. These include protein deficiency, celiac disease, and some intestinal infections.
Adult lactose intolerance is the most common of
all enzyme deficiencies, and it is estimated that 30–50
million Americans have this condition. Some racial
and ethnic populations are affected more than
others. Lactose intolerance is found in as many as
75% of African Americans, Jewish Americans,
Mexican Americans, and Native Americans, and in
90% of Asian Americans. Descendants of Northern
Europeans and some Mediterranean peoples usually
do not develop the condition. Deficiencies in enzymes
other than lactase are extremely rare.

Causes and symptoms
Enzymes play an important role in breaking down
carbohydrates into forms that can pass through the
intestine and be used by the body. Usually they are
721

Carbohydrate intolerance

from these herbs are applied directly to the sores. The
tannic acid in a tea bag can also help dry up the sores
when the wet tea bag is used as a compress. Taking
dandelion (Taraxacum officinale) tea or capsules may
help heal sores and also prevent future outbreaks. Since
canker sores are often brought on by stress, such stressrelieving techniques as meditation, guided imagery, and
certain acupressure exercises may help prevent canker
sores or lessen their severity.

Carbohydrate intolerance

named by adding ase to the name of the substance
they act on, so lactase is the enzyme needed to process
lactose. Cooked starch is broken down in the mouth
to a disaccharide by amylase, an enzyme in the saliva.
The disaccharides maltose, sucrose, and lactose cannot
be absorbed until they have been separated into simple
sugar molecules by their corresponding enzymes present
in the cells lining the intestinal tract. If this process is not
completed, digestion is interrupted.
Although not common, a deficiency in the enzymes
needed to digest lactose, maltose, and sucrose is sometimes present at birth. Intestinal lactase enzymes
usually decrease naturally with age, but this happens
to varying degrees. Because of the uneven distribution
of enzyme deficiency based on race and ethnic heritage,
especially in lactose intolerance, genetics are believed to
play a role in the cause of primary carbohydrate
intolerance.
Digestive diseases such as celiac disease and tropical sprue (which affect absorption in the intestine),
as well as intestinal infections and injuries, can reduce
the amount of enzymes produced. In cancer patients,
treatment with radiation therapy or chemotherapy may
affect the cells in the intestine that normally secrete
lactase, leading to intolerance.
The severity of the symptoms depends on the
extent of the enzyme deficiency, and range from a feeling of mild bloating to severe diarrhea. In the case of a
lactase deficiency, undigested milk sugar remains in the
intestine, which is then fermented by the bacteria normally present in the intestine. These bacteria produce
gas, cramping, bloating, a ‘‘gurgly’’ feeling in the abdomen, and flatulence. In a growing child, the main symptoms are diarrhea and a failure to gain weight. In an
individual with lactase deficiency, gastrointestinal distress begins about 30 minutes to two hours after eating
or drinking foods containing lactose. Food intolerances
can be confused with food allergies, since the symptoms
of nausea, cramps, bloating, and diarrhea are similar.
Sugars that aren’t broken down into one of the
simplest forms cause the body to push fluid into the
intestines, which results in watery diarrhea (osmotic
diarrhea). Diarrhea may sweep other nutrients out of
the intestine before they can be absorbed, causing
malnutrition.

Diagnosis
Carbohydrate intolerance can be diagnosed
using oral tolerance tests. The carbohydrate being
investigated is given by mouth in liquid form and
several blood levels are measured and compared to
722

normal values. This helps evaluate the individual’s
ability to digest the sugar.
To identify lactose intolerance in children and
adults, the hydrogen breath test is used to measure
the amount of hydrogen in the breath. The patient
drinks a beverage containing lactose and the breath
is analyzed at regular intervals. If undigested lactose in
the large intestine (colon) is fermented by bacteria,
various gases are produced. Hydrogen is absorbed
from the intestines and carried by the bloodstream
into the lungs where it is exhaled. Normally there is
very little hydrogen detectable in the breath, so its
presence indicates faulty digestion of lactose.
When lactose intolerance is suspected in infants
and young children, many pediatricians recommend
simply changing from cow’s milk to soy formula and
watching for improvement. If needed, a stool sample
can be tested for acidity. The inadequate digestion of
lactose will result in an increase of acid in the waste
matter excreted by the bowels and the presence of
glucose.

Treatment
Carbohydrate intolerance caused by temporary
intestinal diseases disappears when the condition is
successfully treated. In primary conditions, no treatment exists to improve the body’s ability to produce
the enzymes, but symptoms can be controlled by diet.
Because the degree of lactose intolerance varies so
much, treatment should be tailored for the individual.
Young children showing signs of intolerance should
avoid milk products; infants should switch to soybased formula. Older children and adults can adjust
their intake of lactose depending on how much and
what they can tolerate. For some, a small glass of milk
will not cause problems, while others may be able to
handle ice cream or aged cheeses such as cheddar or
Swiss, but not other dairy products. Generally, small
amounts of lactose-containing foods taken throughout the day are better tolerated than a large amount
consumed all at once.
For those individuals who are sensitive to even very
small amounts of lactose, the lactase enzyme is available
without a prescription. It comes in liquid form for use
with milk. The addition of a few drops to a quart of milk
will reduce the lactose content by 70% after 24 hours
in the refrigerator. Heating the milk speeds up the
process, and doubling the amount of lactase liquid will
result in milk that is 90% lactose free. Chewable lactase
enzyme tablets are also available. Three to six tablets
taken before a meal or snack will aid in the digestion of
GALE ENCYCLOPEDIA OF MEDICINE

Celiac disease—A disease, occurring in both children and adults, which is caused by a sensitivity to
gluten, a protein found in grains. It results in chronic
inflammation and shrinkage of the lining of the
small intestine.
Digestion—The mechanical, chemical, and enzymatic process in which food is converted into the
materials suitable for use by the body.
Enzyme—A substance produced by the body to
assist in a chemical reaction. In carbohydrate intolerance, lack of an enzyme makes it impossible for
one type of sugar to be broken down into a simpler
form so that it can be absorbed by the intestines and
used by the body.
Metabolism—All the physical and chemical
changes that take place within an organism.
Nutrient—Food or another substance that supplies
the body with the elements needed for metabolism.
Sugars—Those carbohydrates having the general
composition of one part carbon, two parts hydrogen, and one part oxygen.

solid foods. Lactose-reduced milk and other products
are also available in stores. The milk contains the same
nutrients as regular milk.
Because dairy products are an important source of
calcium, people who reduce or severely limit their
intake of dairy products may need to consider other
ways to consume an adequate amount of calcium in
their diets.

Prognosis
With good dietary management, individuals with
carbohydrate intolerance can lead normal lives.

Prevention

I Carbon monoxide poisoning
Definition
Carbon monoxide (CO) poisoning occurs when
carbon monoxide gas is inhaled. CO is a colorless,
odorless, highly poisonous gas that is produced by
incomplete combustion. It is found in automobile
exhaust fumes, faulty stoves and heating systems,
fires, and cigarette smoke. Other sources include
woodburning stoves, kerosene heaters, improperly
ventilated water heaters and gas stoves, and blocked
or poorly maintained chimney flues. CO interferes
with the ability of the blood to carry oxygen. The
result is headache, nausea, convulsions, and finally
death by asphyxiation.

Description
Carbon monoxide, sometimes called coal gas, has
been known as a toxic substance since the third century
B.C. It was used for executions and suicides in early
Rome. Today it is the leading cause of accidental poisoning in the United States. According to the Journal of
the American Medical Association, 2,000 Americans die
each year from accidental exposure to CO, and another
2,300 from intentional exposure (suicide). An additional 10,000 people seek medical attention after exposure to CO. The Consumer Products Safety Commission
eported in 2004 that about 64% of unintentional CO
poisoning deaths occur in the home.
Anyone who is exposed to CO will become sick,
and the entire body is involved in CO poisoning.
A developing fetus can also be poisoned if a pregnant
woman breathes CO gas. Infants, people with heart or
lung disease, or those with anemia may be more seriously affected. People such as underground parking
garage attendants who are exposed to car exhausts in a
confined area are more likely to be poisoned by CO.
Firemen also run a higher risk of inhaling CO.

Causes and symptoms

Since the cause of the enzyme deficiency leading to
carbohydrate intolerance is unknown, there is no way
to prevent this condition.
Resources
OTHER

National Institute of Diabetes and Digestive and Kidney
Disease. <http://www.niddk.nih.gov>.

Karen Ericson, RN
GALE ENCYCLOPEDIA OF MEDICINE

Normally when a person breathes fresh air into
the lungs, the oxygen in the air binds with a molecule
called hemoglobin (Hb) that is found in red blood
cells. This allows oxygen to be moved from the lungs
to every part of the body. When the oxygen/hemoglobin complex reaches a muscle where it is needed, the
oxygen is released. Because the oxygen binding process is reversible, hemoglobin can be used over and
over again to pick up oxygen and move it throughout
the body.
723

Carbon monoxide poisoning

KEY TERMS

Carbon monoxide poisoning

Inhaling carbon monoxide gas interferes with this
oxygen transport system. In the lungs, CO competes
with oxygen to bind with the hemoglobin molecule.
Hemoglobin prefers CO to oxygen and accepts it more
than 200 times more readily than it accepts oxygen.
Not only does the hemoglobin prefer CO, it holds on
to the CO much more tightly, forming a complex
called carboxyhemoglobin (COHb). As a person
breathes CO contaminated air, more and more oxygen
transportation sites on the hemoglobin molecules
become blocked by CO. Gradually, there are fewer
and fewer sites available for oxygen. All cells need
oxygen to live. When they don’t get enough oxygen,
cellular metabolism is disrupted and eventually cells
begin to die.
The symptoms of CO poisoning and the speed
with which they appear depend on the concentration
of CO in the air and the rate and efficiency with which
a person breathes. Heavy smokers can start off
with up to 9% of their hemoglobin already bound to
CO, which they regularly inhale in cigarette smoke.
This makes them much more susceptible to environmental CO. The Occupational Safety and Health
Administration (OSHA) has established a maximum
permissible exposure level of 50 parts per million
(ppm) over eight hours.
With exposure to 200 ppm for two to three hours,
a person begins to experience headache, fatigue, nausea, and dizziness. These symptoms correspond to
15–25% COHb in the blood. When the concentration
of COHb reaches 50% or more, death results in a very
short time. Emergency room physicians have the most
experience diagnosing and treating CO poisoning.
The symptoms of CO poisoning in order of
increasing severity include:


headache



shortness of breath



dizziness



fatigue



mental confusion and difficulty thinking



loss of fine hand-eye coordination



nausea and vomiting



rapid heart rate



hallucinations



inability to execute voluntary movements accurately



collapse



lowered body temperature (hypothermia)



coma

724



convulsions



seriously low blood pressure



cardiac and respiratory failure



death

In some cases, the skin, mucous membranes, and
nails of a person with CO poisoning are cherry red or
bright pink. Because the color change doesn’t always
occur, it is an unreliable symptom to rely on for
diagnosis.
Although most CO poisoning is acute, or sudden,
it is possible to suffer from chronic CO poisoning. This
condition exists when a person is exposed to low levels
of the gas over a period of days to months. Symptoms
are often vague and include (in order of frequency)
fatigue, headache, dizziness, sleep disturbances, cardiac symptoms, apathy, nausea, and memory disturbances. Little is known about chronic CO poisoning,
and it is often misdiagnosed.

Diagnosis
The main reason to suspect CO poisoning is evidence that fuel is being burned in a confined area, for
example a car running inside a closed garage, a charcoal grill burning indoors, or an unvented kerosene
heater in a workshop. Under these circumstances, one
or more persons suffering from the symptoms listed
above strongly suggests CO poisoning. In the absence
of some concrete reason to suspect CO poisoning, the
disorder is often misdiagnosed as migraine headache,
stroke, psychiatric illness, food poisoning, alcohol poisoning, or heart disease.
Concrete confirmation of CO poisoning comes
from a carboxyhemoglobin test. This blood test measures the amount of CO that is bound to hemoglobin
in the body. Blood is drawn as soon after suspected
exposure to CO as possible.
Other tests that are useful in determining the
extent of CO poisoning include measurement of
other arterial blood gases and pH; a complete blood
count; measurement of other blood components such
as sodium, potassium, bicarbonate, urea nitrogen,
and lactic acid; an electrocardiogram (ECG); and a
chest x ray.

Treatment
Immediate treatment for CO poisoning is to
remove the victim from the source of carbon monoxide gas and get him or her into fresh air. If the
victim is not breathing and has no pulse, cardiopulmonary resuscitation (CPR) should be started.
GALE ENCYCLOPEDIA OF MEDICINE

Carboxyhemoglobin (COHb)—Hemoglobin that is
bound to carbon monoxide instead of oxygen.
Hemoglobin (Hb)—A molecule that normally
binds to oxygen in order to carry it to our cells,
where it is required for life.
Hypothermia—Development of a subnormal body
temperature.
pH—A measurement of the acidity or alkalinity of
a fluid. A neutral fluid, neither acid nor alkali, has a
pH of 7.

Depending on the severity of the poisoning, 100%
oxygen may be given with a tight fitting mask as soon
as it is available.
Taken with other symptoms of CO poisoning,
COHb levels of over 25% in healthy individuals,
over 15% in patients with a history of heart or lung
disease, and over 10% in pregnant women usually
indicate the need for hospitalization. In the hospital,
fluids and electrolytes are given to correct any imbalances that have arisen from the breakdown of cellular
metabolism.
In severe cases of CO poisoning, patients are given
hyperbaric oxygen therapy. This treatment involves
placing the patient in a chamber breathing 100% oxygen at a pressure of more than one atmosphere (the
normal pressure the atmosphere exerts at sea level).
The increased pressure forces more oxygen into the
blood. Hyperbaric facilities are specialized, and are
usually available only at larger hospitals.

Prognosis
The speed and degree of recovery from CO poisoning depends on the length and duration of exposure to the gas. The half-life of CO in normal room air
is four to five hours. This means that, in four to five
hours, half of the CO bound to hemoglobin will
be replaced with oxygen. At normal atmospheric pressures, but breathing 100% oxygen, the half-life for the
elimination of CO from the body is 50–70 minutes. In
hyperbaric therapy at three atmospheres of pressure,
the half-life is reduced to 20–25 minutes.
Although the symptoms of CO poisoning may
subside in a few hours, some patients show memory
problems, fatigue, confusion, and mood changes for
two to four weeks after their exposure to the gas.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Carbon monoxide poisoning is preventable.
Particular care should be paid to situations where
fuel is burned in a confined area. Portable and permanently installed carbon monoxide detectors that sound
a warning similar to smoke detectors are available for
less than $50. Specific actions that will prevent CO
poisoning include:


stopping smoking. Smokers have less tolerance to
environmental CO



having heating systems and appliances installed by a
qualified contractor to assure that they are properly
vented and meet local building codes



inspecting and properly maintaining
systems, chimneys, and appliances



not using a gas oven or stove to heat the home



not burning charcoal indoors



making sure there is good ventilation if using a
kerosene heater indoors



not leaving cars or trucks running inside the garage



keeping car windows rolled up when stuck in heavy
traffic, especially if inside a tunnel

heating

Resources
PERIODICALS

‘‘Silencing the Silent Killer.’’ USA Today Magazine March
2004: 77.
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
OTHER

‘‘Carbon Monoxide Headquarters.’’ Wayne State
University School of Medicine. <http://www.phypc.med.wayne.edu/>.

Tish Davidson, A.M.
Teresa G. Odle

Carbunculosis see Boils

antigen
I Carcinoembryonic
test
Definition
The carcinoembryonic antigen (CEA) test is a
laboratory blood study. CEA is a substance which is
725

Carcinoembryonic antigen test

KEY TERMS

Carcinoembryonic antigen test

normally found only during fetal development, but may
reappear in adults who develop certain types of cancer.

Purpose
The CEA test is ordered for patients with known
cancers. The CEA test is most commonly ordered
when a patient has a cancer of the gastrointestinal
system. These include cancer of the colon, rectum,
stomach (gastric cancer), esophagus, liver, or pancreas. It is also used with cancers of the breast, lung,
or prostate.
The CEA level in the blood is one of the factors
that doctors consider when determining the prognosis,
or most likely outcome of a cancer. In general, a higher
CEA level predicts a more severe disease, one that is
less likely to be curable. But it does not give clear-cut
information. The results of a CEA test are usually
considered along with other laboratory and/or imaging studies to follow the course of the disease.
Once treatment for the cancer has begun, CEA
tests have a valuable role in monitoring the patient’s
progress. A decreasing CEA level means therapy is
effective in fighting the cancer. A stable or increasing
CEA level may mean the treatment is not working,
and/or that the tumor is growing. It is important to
understand that serial CEA measurements, which
means several done over a period of time, are the
most useful. A single test result is difficult to evaluate,
but a number of tests, done weeks apart, shows trends
in disease progression or regression.
Certain types of cancer treatments, such as hormone therapy for breast cancer, may actually cause the
CEA level to go up. This elevation does not accurately
reflect the state of the disease. It is sometimes referred
to as a ‘‘flare response.’’ Recognition that a rise in
CEA may be temporary and due to therapy is significant. If this possibility is not taken into account, the
patient may be unnecessarily discouraged. Further,
treatment that is actually effective may be stopped or
changed prematurely.
CEA tests are also used to help detect recurrence of
a cancer after surgery and/or other treatment has been
completed. A rising CEA level may be the first sign of
cancer return, and may show up months before other
studies or patient symptoms would raise concern.
Unfortunately, this does not always mean the recurrent
cancer can be cured. For example, only a small percentage of patients with colorectal cancers and rising CEA
levels will benefit from another surgical exploration.
Those with recurrence in the same area as the original
cancer, or with a single metastatic tumor in the liver
726

or lung, have a chance that surgery will eliminate
the disease. Patients with more widespread return of
the cancer are generally not treatable with surgery. The
CEA test will not separate the two groups.
Patients who are most likely to benefit from non–
standard treatments, such as bone marrow transplants, may be determined on the basis of CEA values,
combined with other test results. CEA levels may be
one of the criteria for determining whether the patient
will benefit from more expensive studies, such as CT
scan or MRI.

Precautions
The CEA test is not a screening test for cancer.
It is not useful for detecting the presence of cancer.
Many cancers do not produce an increased CEA
level. Some noncancerous diseases, such as hepatitis, inflammatory bowel disease, pancreatitis, and
obstructive pulmonary disease, may cause an elevated
CEA level.

Description
Determination of the CEA level is a laboratory
blood test. Obtaining a specimen of blood for the
study takes only a few minutes. CEA testing should
be covered by most insurance plans.

Preparation
No preparation is required.

Aftercare
None.

Risks
There are no complications or side effects of this
test. However, the results of a CEA study should be
interpreted with caution. A single test result may not
yield clinically useful information. Several studies over
a period of months may be needed.
Another concern is the potential for false positive
as well as false negative results. A false positive result
means the test shows an abnormal value when cancer
is not present. A false negative means the test reveals a
normal value when cancer actually is present.

Normal results
The absolute numbers which are considered normal vary from one laboratory to another. Any results
GALE ENCYCLOPEDIA OF MEDICINE

Abnormal results
A single abnormal CEA value may be significant,
but must be regarded cautiously. In general, very high
CEA levels indicate more serious cancer, with a poorer
chance for cure. But some benign diseases and certain
cancer treatments may produce an elevated CEA test.
Cigarette smoking will also cause the CEA level to be
abnormally high.
Resources
BOOKS

Cooper, Dennis L. ‘‘Tumor Markers.’’ In Cecil Textbook of
Medicine, edited by J. Claude Bennet and Fred Plum.
Philadelphia: W. B. Saunders Co., 1996.

Ellen S. Weber, MSN

Carcinoid tumors see Neuroendocrine
tumors
Cardiac arrest see Sudden cardiac death
Cardiac arrhythmias see Arrhythmias

Description
A cardiac blood pool scan is sometimes called
equilibrium radionuclide angiocardiography or gated
(synchronized) cardiac blood pool imaging. A multiplegated acquisition (MUGA) scan is a variation of
this test.
To perform a cardiac blood pool scan, the patient
lies under a special gamma scintillation camera that
detects radiation. A protein tagged with a radioactive
marker (usually technetium-99m) is injected into the
patient’s forearm.
The camera is synchronized with an electrocardiogram (ECG) to take a picture at specific times in the
cycle of heart contraction and relaxation. When data
from many sequential pictures is processed by a computer, a doctor can analyze whether the left ventricle is
functioning normally.
The patient needs to remain silent and motionless
during the test. Sometimes the patient is asked to
exercise, then another set of pictures is taken for
comparison. This test normally takes about 30
minutes.

Preparation
No changes in diet or medication are necessary.
An ECG will probably be done before the test.

I Cardiac blood pool scan
Definition
A cardiac blood pool scan is a non-invasive test
that uses a mildly radioactive marker to observe the
functioning of the left ventricle of the heart.

Purpose
The left ventricle is the main pump for distributing
blood through the body. A cardiac blood pool scan is
used to determine how efficiently the left ventricle is
working. The scan can detect aneurysms of the left
ventricle, motion abnormalities caused by damage to
the heart wall, cardiac shunts between the left and
right ventricle, and coronary occlusive artery disease.

Precautions
Pregnant women are the only patients who should
not participate in a cardiac blood pool scan. However,
the accuracy of the results may be affected if the
patient moves during imaging, has had other recent
nuclear scans, or has an irregular heartbeat.
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
The patient may resume normal activities
immediately.

Risks
Cardiac blood pool scans are a safe and effective
way of measuring left ventricle function. The only risk
is to the fetus of a pregnant woman.

Normal results
A computer is used to process the information
from the test, then the results are analyzed by a doctor.
A normally functioning left ventricle will contract
symmetrically, show even distribution of the radioactively tagged protein, and eject about 55–65% of
volume of blood it holds on each contraction.

Abnormal results
Patients with damage to the ventricle or heart
wall will show an uneven distribution of the
727

Cardiac blood pool scan

reported should come with information regarding the
testing facility’s normal range.

Cardiac catheterization

KEY TERMS
Aneurysm—A sac or bulge that forms because of a
weak spot in the wall of an artery or heart chamber.
Cardiac shunt—A defect in the wall of the heart
that allows blood from different chambers to mix.
Coronary occlusive artery disease—Blockage of
the arteries that supply blood to the heart; frequently a precursor to a heart attack.
Electrocardiogram (ECG)—A graph that shows the
electrical charges that trigger the heart to contract.
Heart abnormalities alter the graph, giving clues to
the source of the abnormality.
Ventricle—One of the two bottom chambers
of the heart (the heart has four chambers). The
left ventricle acts as the body’s main pump for
blood.

the heart’s right side, tricuspid and pulmonary valve
function are evaluated, in addition to measuring pressures of and collecting blood samples from the right
atrium, ventricle, and pulmonary artery. Left-sided
heart catheterization is performed by way of a catheter
through an artery which tests the blood flow of the
coronary arteries, function of the mitral and aortic
valves, and left ventricle.

Purpose
The primary reason for conducting a cardiac
catheterization is to diagnose and manage persons
known or suspected to have heart disease, a frequently
fatal condition that leads to 1.5 million heart attacks
annually in the United States.
Symptoms and diagnoses that may lead to performing this procedure include:


chest pain, characterized by prolonged heavy pressure or a squeezing pain



abnormal treadmill stress test



myocardial infarction, also known as a heart attack



congenital heart defects, or heart problems that originated from birth

BOOKS



a diagnosis of valvular-heart disease

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.



a need to measure the heart muscle’s ability to pump
blood

radiopharmaceutical. The volume of blood ejected in
each contraction will be less than 55%.
Resources

Tish Davidson, A.M.

I Cardiac catheterization
Definition
Cardiac catheterization (also called heart catheterization) is a diagnostic procedure which does a comprehensive examination of how the heart and its blood
vessels function. One or more catheters is inserted
through a peripheral blood vessel in the arm (antecubital artery or vein) or leg (femoral artery or vein) with
x–ray guidance. This procedure gathers information
such as adequacy of blood supply through the coronary
arteries, blood pressures, blood flow throughout chambers of the heart, collection of blood samples, and x rays
of the heart’s ventricles or arteries.
A test that can be performed on either side of the
heart, cardiac catheterization checks for different
functions in both the left and right sides. When testing
728

Typically performed along with angiography, a
technique of injecting a dye into the vascular system
to outline the heart and blood vessels, a catheterization can aid in the visualization of any blockages,
narrowing, or abnormalities in the coronary arteries.
If these signs are visible, the cardiologist may assess
the patient’s need and readiness for coronary bypass
surgery, or perhaps a less invasive approach, such as
dilation of a narrowed blood vessel either surgically or
with the use of a balloon (angioplasty).
When looking at the left side of the heart, fluoroscopic guidance also allows the following diagnoses to
be assessed:


enlargement of the left ventricle



ventricular aneurysms (abnormal dilation of a blood
vessel)



narrowing of the aortic valve



insufficiency of the aortic or mitral valve



the detour of blood from one side of the heart to the
other due to septal defects (also known as shunting)
GALE ENCYCLOPEDIA OF MEDICINE

Cardiac catheterization is categorized as an ‘‘invasive’’ procedure which involves the heart, its valves,
and coronary arteries, in addition to a large artery in
the arm or leg. Due to the nature of the test, it is
important to evaluate for the following conditions
before considering this procedure:




A diagnosis of a bleeding disorder, poor kidney function, or debilitation. Any of these pre-existing conditions typically raises the risk of the catheterization
procedure and may be reason to cancel the
procedure.
A diagnosis of heart valve disease. If this is detected,
antibiotics may be given before the test to prevent
inflammation of the membrane which lines the heart
(endocarditis).

Description
To understand how a cardiac catheterization is
able to diagnose and manage heart disease, the basic
workings of the heart muscle must also be understood.
Just as the body relies on a constant supply of blood to
aid in its everyday functions, so does the heart. The
heart is made up of an intricate web of blood vessels
(coronary arteries) that ensure an adequate supply of
blood rich in oxygen and nutrients. It is easy to see
how an abnormality in any of these arteries can be
detrimental to the heart’s function. These abnormalities cause the heart’s blood flow to decrease and result
in the condition known as coronary artery disease or
coronary insufficiency.
Catheterization is a valuable tool in detecting and
treating abnormalities of the heart. Through the use of
fluoroscopic (x ray) guidance, a catheter, which may
resemble a balloon-tipped tube, is strung through the
veins or arteries into the heart, so the cardiologist can
monitor a body’s various functions at each moment.
Generally a test that lasts two to three hours, a
patient should expect the following prior to and during the catheterization procedure:


A mild sedative may be given that will allow the
patient to relax but remain conscious during the test.



An intravenous needle will be inserted in the arm to
administer medication. Electrodes will be attached to
the chest to enable the painless procedure known as
an electrocardiograph.



Prior to inserting a catheter into an artery or vein in
the arm or leg, the incision site will be made numb by
injecting a local anesthetic. When the anesthetic is
injected it may feel like a pin-prick followed by a

GALE ENCYCLOPEDIA OF MEDICINE

quick stinging sensation. Pressure may also be
experienced as the catheter travels through the
blood vessel.


After the catheter is guided into the coronary-artery
system, a dye (also called a radiocontrast material) is
injected to aid in the identification of any abnormalities
of the heart. During this time, the patient may experience a hot, flushed feeling or a quickly passing nausea.
Coughing or breathing deeply aids in any discomfort.



Medication may be given during the procedure if
chest pain is experienced, and nitroglycerin may
also be administered to allow expansion of the
heart’s blood vessels.



When the test is complete, the physician will remove
the catheter and close the skin with several sutures or
tape.

Preparation
Prior to the cardiac catheterization procedure, it is
important to relay information to the physician or
nurse regarding allergies to shellfish (such as shrimp
or scallops) which contain iodine, iodine itself, or the
dyes that are commonly used in other diagnostic tests.
Because this procedure is categorized as a surgery,
the patient will be instructed not to eat or drink anything for at least six hours prior to the test. Just before
the test begins, the patient will urinate and change into
a hospital gown, then lie flat on a padded table that
may also be tilted in order for the heart to be examined
from a variety of angles.

Aftercare
While cardiac catheterization may be performed
on an out-patient basis, a patient may require close
monitoring following the procedure while remaining
in the hospital for at least 24 hours. The patient will
be instructed to rest in bed for at least eight hours
immediately after the test. If the catheter was inserted
into a vein or artery in the leg or groin area, the leg will
be kept extended for four to six hours. If a vein or artery
in the arm was used to insert the catheter, the arm will
need to remain extended for a minimum of three hours.
The patient should expect a hard ridge to form over
the incision site that diminishes as the site heals. Bluish
discoloration under the skin at the point of insertion
should also be expected but fades in two weeks. It is also
not uncommon for the incision site to bleed during the
first 24 hours following surgery. If this should happen,
the patient should apply pressure to the site with a clean
tissue or cloth for 10–15 minutes.
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Cardiac catheterization

Precautions

Cardiac catheterization

Normal results
Normal findings from a cardiac catheterization
will indicate no abnormalities of heart chamber size
or configuration, wall motion or thickness, the direction of blood flow, or motion of the valves. Smooth
and regular outlines on the x ray indicate normal
coronary arteries.

The catheter
extends from the
groin area to
the heart.

(Illustration by Argosy Inc.)

Risks
Similar to all surgical procedures, the cardiac catheterization test does involve some risks. Complications
that may occur during the procedure include


cardiac arrhythmias (an irregular heart beat)



pericardial tamponade (a condition that causes
excess pressure in the pericardium which affects the
heart due to accumulation of excess fluid)



the rare occurrence of myocardial infarction (heart
attack) or stroke may also develop due to clotting or
plaque rupture of one or more of the coronary or
brain arteries.

An essential part of the catheterization is measuring intracardiac pressures, or the pressure in the
heart’s chambers and vessels. Pressure readings that
are higher than normal are significant for a patient’s
overall diagnosis. The pressure readings that are
lower, other than those which are produced as a result
of shock, typically are not significant.
An ejection fraction, or a comparison of how
much blood is ejected from the heart’s left ventricle
during its contraction phase with a measurement of
blood remaining at the end of the left ventricle’s
relaxation phase, is also determined by performing a
catheterization. The cardiologist will look for a normal ejection fraction reading of 60–70%.

Abnormal results
Cardiac catheterization provides valuable still and
motion x-ray pictures of the coronary arteries that
help in diagnosing coronary artery disease, poor
heart function, disease of the heart valves, and septal
defects (a defect in the septum, the wall that separates
two heart chambers).
The most prominent sign of coronary artery disease is the narrowing or blockage in the coronary
arteries, with narrowing that is greater than 70% considered significant. A clear indication for intervention
(by angioplasty or surgery) is a finding of significant
narrowing of the left main coronary artery and/or
blockage or severe narrowing in the high, left anterior
descending coronary artery.

Before left-side catheterization is performed,
the anticoagulant medication heparin may be administered. This drug helps decrease the risk of the
development of a blood clot in an artery (thrombosis)
and blood clots traveling throughout the body
(embolization).

A finding of impaired wall motion is an additional
indicator of coronary artery disease, aneurysm, an
enlarged heart, or a congenital heart problem. Using
the findings from an ejection fraction test which measures wall motion, cardiologists look at an ejection
fraction reading under 35% as increasing the risk of
complications while also decreasing a successful long
term or short term outcome with surgery.

The risks of the catheterization procedure increase
in patients over the age of 60, those who have severe
heart failure, or persons with serious valvular heart
disease.

Detecting the difference in pressure above and
below the heart valve can verify heart valve disease.
The greater narrowing correlates with the higher pressure difference.

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ORGANIZATIONS

American Heart Association. 7320 Greenville Ave.
Dallas, TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Aneurysm—An abnormal dilatation of a blood vessel, usually an artery. It can be caused by a congenital defect or weakness in the vessel’s wall.
Angiography—In cardiac catheterization, a picture
of the heart and coronary arteries is seen after
injecting a radiopaque substance (often referred to
as a dye) throughout the veins and arteries.
Angioplasty—An alternative to vascular surgery, a
balloon catheter is used to mechanically dilate the
affected area of the artery and enlarge the constricted or narrowed segment.

Cardiac conduction disorder see Heart block

Aortic valve—The valve between the heart’s left
ventricle and ascending aorta that prevents regurgitation of blood back into the left ventricle.

Cardiac mapping see Electrophysiology
study of the heart

Catheter—A tube made of elastic, elastic web, rubber, glass, metal, or plastic used to evacuate or
inject fluids into the body. In cardiac catheterization, a long, fine catheter is used for passage
through a blood vessel into the chambers of the
heart.
Coronary bypass surgery—A surgical procedure
which places a shunt to allow blood to travel from
the aorta to a branch of the coronary artery at a
point past an obstruction.
Left anterior descending coronary artery (LAD)—
One of the heart’s coronary artery branches from
the left main coronary artery which supplies blood
to the left ventricle.
Mitral valve—The bicuspid valve which is between
the left atrium and left ventricle of the heart.
Pulmonary valve—The heart valve which is positioned between the right ventricle and the opening
into the pulmonary artery.
Shunt—A passageway (or an artificially created
passageway) that diverts blood flow from one
main route to another.
Tricuspid valve—The right atrioventricular valve of
the heart.

To confirm septal defects, a catheterization measures oxygen content on both the left and right sides of
the heart. The right heart pumps unoxygenated blood
to the lungs, and the left heart pumps blood that contains oxygen from the lungs to the rest of the body.
Right side elevated oxygen levels indicate left-to-right
atrial or ventricular shunt. A left side that experiences
decreased oxygen indicates a right-to-left shunt.
GALE ENCYCLOPEDIA OF MEDICINE

Beth A. Kapes

Cardiac compression see Cardiac
tamponade

I Cardiac rehabilitation
Definition
Cardiac rehabilitation is a comprehensive exercise,
education, and behavioral modification program
designed to improve the physical and emotional condition of patients with heart disease.

Purpose
Heart attack survivors, bypass and angioplasty
patients, and individuals with angina, congestive
heart failure, and heart transplants are all candidates
for a cardiac rehabilitation program. Cardiac rehabilitation is prescribed to control symptoms, improve
exercise tolerance, and improve the overall quality of
life in these patients.

Precautions
A cardiac rehabilitation program should be implemented and closely monitored by a trained team of
healthcare professionals.

Description
Cardiac rehabilitation is overseen by a specialized team of doctors, nurses, and other healthcare
professionals. Members of the cardiac rehabilitation
team may include a dietician or nutritionist, physical
therapist, exercise physiologist, psychologist, vocational counselor, occupational therapist, and social
worker. The program frequently begins in a hospital
731

Cardiac rehabilitation

Resources

KEY TERMS

Cardiac rehabilitation

setting and continues on an outpatient basis after
the patient is discharged over a period of six to 12
months.
Components of a cardiac rehabilitation program
vary by individual clinical need, and each program will
be carefully constructed for the patient by his or her
rehabilitation team.


Exercise. Exercise programs typically start out
slowly, with simple range-of-motion arm and leg
exercises. Walking and stair climbing soon follow.
Blood pressure is carefully monitored before and
after exercise sessions, and patients are taught how
to measure their heart rate and evaluate any possible
cardiac symptoms during each session. Patients
with advanced coronary disease may require continuous ECG monitoring throughout their exercise sessions. Once discharged from the hospital, the patient
works with his cardiac team to create an individual
exercise plan.



Diet. Cardiac patients will work with a nutritionist or
dietician to develop a low-fat, low-cholesterol diet
plan. Patients with high blood pressure may be put
on a salt-restricted diet and instructed to limit alcohol intake. Weight loss may also be a goal with obese
cardiac patients.



Counseling. A psychologist or social worker can help
cardiac patients with issues that may be contributing
to their heart condition, such as stress and anxiety.
Relaxation techniques may be taught to patients to
help them deal with these feelings. Cardiac patients
frequently experience a period of depression, and
group or individual counseling can be beneficial in
overcoming these feelings. Vocational counselors
can assist cardiac patients in returning to the
workforce.



Education. The patient and family should be fully
educated on the physical limitations of the patient,
his recommended diet and exercise plan, his emotional status, and the lifestyle changes required to
improve the patient’s overall health.



Smoking cessation. Cardiac patients who smoke are
twice as likely to have a heart attack in the following
five years than non-smoking patients. These patients
are strongly encouraged to enroll in a smoking cessation program, which typically includes patient
education and behavioral counseling. Nicotine replacement therapy, which uses nicotine patches, nose
spray, or gum to wean patients off of cigarettes,
may also be part of the program. Antidepressants
and anti-anxiety medication may be helpful in some
cases.

732

This 40-year-old male is working out on a treadmill, monitored
by his physician, following heart surgery. (Custom Medical
Stock Photo. Reproduced by permission.)

Aftercare
Long-term maintenance is a critical feature of
cardiac rehabilitation. Patients require support from
their healthcare team, family, and friends to continue
the lifestyle changes they implemented during the
rehabilitation period.

Risks
The risks of another heart attack during cardiac
rehabilitation are slight, and greatly reduced by careful, continuous monitoring of the physical status of
the patient.

Normal results
The outcome of the cardiac rehabilitation program
depends on a number of variables, including patient
GALE ENCYCLOPEDIA OF MEDICINE

Angina—Chest pain.
Bypass surgery—A surgical procedure that grafts
blood vessels onto arteries to reroute the blood flow
around blockages in the arteries (arteriosclerosis).

follow-through, type and degree of heart disease, and
the availability of an adequate support network for the
patient. Patients who successfully complete the program will ideally reach an age-appropriate level of physical activity and be able to return to the workforce and/
or other daily activities.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave.
Dallas, TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

the pericardium is damaged by cancer. Blunt or penetrating injury from trauma to the chest or heart can
also result in cardiac tamponade when large amounts
of blood fill the pericardium. Tamponade can also
occur during heart surgery.
When the heart is compressed by the surrounding
fluid, three conditions occur: a reduced amount of blood
is pumped to the body by the heart, the lower chambers
of the ventricles are filled with a less than normal
amount of blood, and higher than normal blood pressures occur inside the heart, caused by the pressure of the
fluid pushing in on the heart from the outside.
When tamponade occurs because of trauma, the
sound of the heart beats can become faint, and
the blood pressure in the arteries decreases, while the
blood pressure in the veins increases.
In cases of tamponade caused by more slowly
developing diseases, shortness of breath, a feeling of
tightness in the chest, increased blood pressure in the
large veins in the neck (the jugular veins), weight gain,
and fluid retention by the body can occur.

Paula Anne Ford-Martin

Diagnosis

I Cardiac tamponade
Definition
Cardiac tamponade occurs when the heart is
squeezed by fluid that collects inside the sac that surrounds it.

Description
The heart is surrounded by a sac called the pericardium. When this sac becomes filled with fluid, the
liquid presses on the heart, preventing the lower chambers of the heart from properly filling with blood.
Because the lower chambers (the ventricles) cannot fill with the correct amount of blood, less than
normal amounts of blood reach the lungs and the rest
of the body. This condition is very serious and can be
fatal if not treated.

Causes and symptoms
Fluid can collect inside the pericardium and compress the heart when the kidneys do not properly
remove waste from the blood, when the pericardium
swells from unknown causes, from infection, or when
GALE ENCYCLOPEDIA OF MEDICINE

When cardiac tamponade is suspected, accurate
diagnosis can be life-saving. The most accurate way to
identify this condition is by using a test called an
echocardiogram. This test uses sound waves to create
an image of the heart and its surrounding sac, making
it easy to visualize any fluid that has collected inside
the sac.

Treatment
If the abnormal fluid buildup in the pericardial
sac is caused by cancer or kidney disease, drugs used
to treat these conditions can help lessen the amount
of fluid collecting inside the sac. Drugs that help
maintain normal blood pressure throughout the
body can also help this condition; however, these
drugs are only a temporary treatment. The fluid
within the pericardium must be drained out to reduce
the pressure on the heart and restore proper heart
pumping.
The fluid inside the pericardium is drained by
inserting a needle through the chest and into the sac
itself. This allows the fluid to flow out of the sac,
relieving the abnormal pressure on the heart. This
procedure is called pericardiocentesis. In severe cases,
a tube (catheter) can be inserted into the sac or a
section of the sac can be surgically cut away to allow
for more drainage.
733

Cardiac tamponade

KEY TERMS

Cardiomyopathy

KEY TERMS
Pericardiocentesis—A procedure used to drain
fluid out of the sac surrounding the heart. This
is done by inserting a needle through the chest
and into the sac.

elderly persons, but can also affect infants, children,
and adolescents.
There are four major types of cardiomyopathy:


Dilated (congestive cardiomyopathy). This is the most
common form of the disease. The heart cavity is
enlarged and stretched (cardiac dilation), which
results in weak and slow pumping of the blood,
which in turn can result in the formation of blood
clots. Abnormal heart rhythms (arrhythmias) and
disturbances in the electrical conduction processes
in the heart may also occur. Most patients with this
type of cardiomyopathy develop congestive heart
failure. There is also a genetically-linked cardiac disease, Barth syndrome, that can cause dilated cardiomyopathy. This syndrome affects male children, and
is usually diagnosed at birth or within the first few
months of life. Pregnant women during the last trimester of pregnancy or after childbirth may develop a
type of dilated cardiomyopathy referred to as peripartum cardiomyopathy.



Hypertrophic cardiomyopathy. With this type of cardiomyopathy, the muscle mass of the left ventricle
enlarges, or hypertrophies. In hypertrophic obstructive cardiomyopathy (HOCM), the septum (wall)
between the two heart ventricles (the pumping chambers) becomes enlarged and obstructs blood flow from
the left ventricle. The thickened wall can also distort
one leaflet of the mitral valve, which results in
leakage. HOCM is most common in young adults.
HOCM is often hereditary, caused by genetic mutations in the affected person’s DNA. The disease is
either inherited through one parent who is a carrier
or through both parents who each contribute a defective gene. HOCM is also referred to as asymmetrical
septal hypertrophy (ASH) or idiopathic hypertrophic
subaortic stenosis (IHSS). In another form of hypertrophic cardiomyopathy, non-obstructive cardiomyopathy, the enlarged heart muscle does not obstruct the
blood flow through the heart.



Restrictive cardiomyopathy. This is a less common
type of cardiomyopathy, in which the heart muscle
of the ventricles becomes rigid. Restrictive cardiomyopathy affects the diastolic function of the heart,
that is, it affects the period when the heart is relaxing
between contractions. Since the heart cannot relax
adequately between contractions, it is harder for the
ventricles to fill with blood between heartbeats. This
type of cardiomyopathy is usually the result of
another disease.



Arrhythmogenic right ventricular cardiomyopathy
(ARVC). ARVC is very rare and is believed to be
an inherited condition. With ARVC, heart muscle

Prognosis
This condition is life-threatening. However, drug
treatments can be helpful, and surgical treatments can
successfully drain the trapped fluid, though it may
reaccumulate. Some risk of death exists with surgical
drainage of the accumulated fluid.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave.
Dallas, TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dominic De Bellis, PhD

Cardiac tumors see Myxoma
Cardiogenic shock see Shock

I Cardiomyopathy
Definition
Cardiomyopathy is a chronic disease of the heart
muscle (myocardium), in which the muscle is abnormally enlarged, thickened, and/or stiffened. The weakened heart muscle loses the ability to pump blood
effectively, resulting in irregular heartbeats (arrhythmias) and possibly even heart failure.

Description
Cardiomyopathy, a disease of the heart muscle,
primarily affects the left ventricle, which is the main
pumping chamber of the heart. The disease is often
associated with inadequate heart pumping and other
heart function abnormalities. Cardiomyopathy is not
common (affecting about 50,000 persons in the United
States) but it can be severely disabling or fatal. Severe
cases may result in heart failure and will require a heart
transplant for patient survival. Cardiomyopathy is a
heart condition that not only affects middle-aged and
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GALE ENCYCLOPEDIA OF MEDICINE

Causes & symptoms
Cardiomyopathy may be caused by many different factors, including viral infections (e.g., myocarditis), heart attacks, alcoholism, long-term, severe high
blood pressure, genetic neuromuscular diseases (e.g.,
muscular dystrophies and ataxias), genetic metabolic
disorders, complications from AIDS, and other reasons that have not yet been identified (idiopathic
cardiomyopathy). Cardiomyopathy caused by heart
attacks (referred to as ischemic cardiomyopathy)
results from scarring in the heart muscle. Larger
scars or more numerous heart attacks increases the
risk that ischemic cardiomyopathy will develop.
Alcoholic cardiomyopathy usually develops about 10
years after sustained, heavy alcohol consumption.
Other toxins that may cause cardiomyopathy include
drugs and radiation exposure.
The major symptoms of cardiomyopathy include:


shortness of breath



temporary and brief loss of consciousness, especially
after engaging in activity



lightheadness, especially after engaging in activity



decreased ability to tolerate physical exertion



fatigue



dizziness



palpitations, that is, the sensation of feeling the heart
beat



chest pain (angina), whereby there is a feeling of
sharp and unrelenting pressure in the middle of the
chest (especially experienced by persons whose cardiomyopathy is a result of a previous heart attack)



high blood pressure

Other symptoms that may be associated with
cardiomyopathy include:


abdominal swelling or enlargement



swelling of legs or ankles



low amount of urine during the daytime, but a need
to urinate at night



decreased alertness and difficulty concentrating

GALE ENCYCLOPEDIA OF MEDICINE



cough



loss of appetite

Diagnosis
A complete physical examination and health history review by a health care provider is recommended
if a person is suspected to have cardiomyopathy. The
examination may reveal the presence of an irregular
heartbeat, heart murmur, or other abnormal heart and
breath sounds.
Various invasive and non-invasive tests are performed as diagnostic tools for cardiomyopathy. An
echocardiogram is the most informative noninvasive
test for diagnosing the type of cardiomyopathy and
the degree of dysfunction in the heart muscle. High
frequency sound waves produce moving images of the
beating heart on a video screen, which allows the
measurement of muscle thickness, size, pumping ability, degree of obstruction, chamber size, and heart
valve movement.
The use of non-invasive radiation-based imaging
procedures, such as chest radiography, computed
tomography (CT), or magnetic resonance imaging
(MRI) procedures show the size, shape, and structure
of the heart. If dilated cardiomyopathy is suspected,
one of these techniques is performed first to see if the
heart is enlarged and whether there is any fluid accumulation in the lungs.
An electrocardiogram (EKG) is a non-invasive
procedure where electrodes are placed on the person’s
limbs and chest wall to provide a graphic record of the
electrical activity of the heart. This test can show the
amount of heart enlargement and reveal abnormal
heart rhythms. Children with a normal echocardiogram may have an abnormal EKG, indicating that
they may be a carrier of the cardiomyopathy gene
and may develop the disease later in life. A person
may also wear a Holter monitor, which is an external
device that continuously records heart rhythms. The
monitor can identify irregular heart rhythms associated with dilated, hypertrophic, or restrictive
cardiomyopathy.
Genetic studies may help in understanding the
cause of cardiomyopathy, since the disease may be a
symptom of another genetic disorder. If a child under
the age of 4 has cardiomyopathy, metabolic screening
should be performed, for certain metabolic disorders
with cardiomyopathy as a symptom can be controlled
with a change in diet, drug therapy, or by a bone marrow transplant, which may reduce or reverse the progression of the cardiomyopathy. Since cardiomyopathy
735

Cardiomyopathy

cells become disorganized and damaged and are
replaced by fatty tissues. The damage appears to be
a result of the body’s inability to remove damaged
cells. The damaged cells are replaced with fat, leading
to abnormal electrical activity (arrhythmias) and
abnormal heart contractions. ARVC is the most
common cause of sudden death in athletes.

Cardiomyopathy

can be inherited and present initially without signs or
symptoms, relatives of a patient with the disease should
be screened periodically for evidences of the disease.

relieve venous congestion. These drugs may result in
side effects, so the patient must be carefully monitored
to prevent complications.

Invasive procedures, which involve the use of
anesthesia, are used to determine the severity of the disease. In the radionuclide ventriculogram procedure, a
low-dose radioactive material is injected into a vein and
flows to the heart. The heart is photographed with a
special camera to assess the contraction and filling of
the ventricles at rest and with activity. Cardiac catheterization involves insertion of thin, flexible plastic tubes
(catheters) into the heart from a blood vessel in the
groin area. A dye is then injected that can indicate
blood pressures, blood flow within the heart, and
blockages in the arteries. Although rarely used, a heart
muscle biopsy, where the doctor removes a few, tiny
pieces of the heart for laboratory studies, can aid in
diagnosing possible infections in the heart or metabolic
abnormalities. An electrophysiology study is similar to
heart catheterization. Catheters with fine wires are
inserted through veins in the groin area into the heart.
Electrical stimuli applied through the wires can indicate
abnormal conduction pathways, arrhythmias, effectiveness of drugs, and the need for an implanted defibrillator.

When drugs are not effective or when arrhythmias
require regulation, a pacemaker or a defibrillator may
be implanted surgically into the patient. The procedures for implanting both devices involves placing a
small mechanical device under the skin of the chest or
abdomen with wire leads threaded through veins to
the heart. A pacemaker is used to monitor and stabilize slow heartbeats, while a defibrillator (‘‘an emergency room in the heart’’) detects and treats fast and
potentially lethal heart rhythms. Since sudden death
may occur in patients with cardiomyopathy, defibrillators are often recommended for persons who show
evidence of arrhythmias.

Treatment
Although there is a long list of possible causes for
cardiomyopathy, few are directly treatable or curable.
Therefore, most therapy is directed towards treating
the effects of the disease on the heart. If cardiomyopathy is diagnosed at an advanced stage, a critically ill
patient will require immediate life-saving measures
such as placement of a breathing tube and administration of medicines to improve heart function and blood
pressure. Once the patient is stabilized, long-term therapy needs, such as oral medication, pacemakers, surgery, or heart transplantation, will be identified.
Initial treatments for cardiomyopathy for patients
diagnosed in the earlier stages of cardiomyopathy
include drug therapy to relieve heart failure, to decrease
oxygen requirements and workload of the heart (by
relaxing the arteries in the body), and to regulate abnormal heartbeats. Drugs that help the heart contract
include digoxin for at-home use and dopamine, dobutamine, and milrinone for in-hospital use. Diuretics help
relieve fluid overloads in heart failure. Vasodilators,
ACE-inhibitors, and beta blockers dilate blood vessels
in the body and lower blood pressure, thus reducing the
workload for the heart. For patients at risk of developing blood clots, anticoagulation medication or blood
thinners such as heparin or coumadin are prescribed
along with diuretics such as Lasix and aldactone to
736

For heart failure symptoms associated with
restricted blood flow from the ventricles, septal myomectomy, which is considered major heart surgery, is
sometimes recommended. This procedure involves
surgical removal of the part of the thickened septal
muscle that blocks the blood flow. In some cases, the
mitral valve is replaced with an artificial valve.
However, the procedure does not prevent sudden
death due to hear arrhythmias nor does it stop the
disease from progressing.
Since cardiomyopathy often becomes progressively
worse, the heart can reach a state where it no longer
responds to medication or to surgery. The treatment of
‘‘last resort’’ is a heart transplant, when the patient
exhibits severe heart failure symptoms. A transplant
can cure the symptoms of heart failure, but the surgery
carries significant risks, such as infection, organ rejection, and side effects of required medications.
There are surgical procedures that can be implemented to sustain life until a transplant donor
becomes available. Left Ventricular Assist Device
(LVAD) provides mechanical circulatory support,
while Dynamic Cardiomyoplasty is a procedure
whereby a skeletal-muscular flap, created from a
patient’s chest muscle, is first taught to contract and
then is wrapped around the heart to aid in contraction.

Alternative treatment
Alternative treatments are directed towards control of the effects of heart disease. Exercise, diet, nutrition, herbal therapies, stress reduction, and other
life style changes (e.g., cessation of smoking) can all
be used to complement conventional treatments.
Certain herbs such as fox glove (Digitalis purpurea)
and lily of the valley (Convallaria majalis) contain
GALE ENCYCLOPEDIA OF MEDICINE

Arrhythmia—An abnormal rhythm or irregularity
of the heartbeat. The heartbeat may either be too
fast (tachycardia) or too slow (bradicardia).
Arrhythmias may cause symptoms such as palpitation or light-headedness, but many have more serious consequences, including sudden death.
Congestive heart failure—Potentially lethal condition in which congestion develops in the lungs that
is produced by a heart attack, poorly controlled or
uncontrolled hypertension, or disease processes
that weaken the heart
Hypertrophy—Literally means an increase in the
muscle mass (or weight) of the heart.
Mitral valve leaflets—The mitral valve is made up
of two valve leaflets (the anteromedial leaflet and
the posterolateral leaflet) and a ring around the
valve, known as the mitral valve annulus. The
orientation of the two leaflets resembles a bishop’s
miter, which is where the valve receives its name.
Myocardium—The muscular wall of the heart
located between the inner endocardial layer and
the outer epicardial layer.
Noninvasive —Refers to tests that generally do not
invade the integrity of the body, such as echocardiography or electrocardiography. (Cardiac cathetherization, on the other hand, in which catheters
are introduced through blood vessels into the heart,
is an example of an invasive test).
Septum (ventricular septum)—That portion of the
heart wall that divides the right and left ventricles.
Ventricles —The two main (lower) pumping chambers of the heart; the right and left ventricles pump
blood to the lungs and aorta, respectively.

cardiac glycosides that make them particularly potent
and may cause dangerous side effects. Their use should
be supervised only be a qualified medical herbalist,
with the concurrence of the primary conventional
health care provider. Even the use of less potent herbs
that improve cardiac function, such as hawthorn
(Crataegus laevigata), should be approved by the conventional health care provider and administered under
the supervision of a medical herbalist.

Prognosis
Long-term prognosis can be unpredictable, as
there can be a wide range of severities and outcomes
GALE ENCYCLOPEDIA OF MEDICINE

associated with the disease. There is no cure, but some
symptoms and complications can be managed and
controlled with medication and implantable devices
or with a heart transplant.

Prevention
Prevention of cardiomyopathy is focused on controlling risk factors for heart disease, which includes
maintaining a healthy weight, exercising regularly,
eating a well-balanced nutritious diet, and avoiding
or minimizing smoking.
Resources
BOOKS

Dilated Cardiomyopathy: A Medical Dictionary,
Bibliography, and Annotated Research Guide to
Internet Resources. San Diego, CA: Icon Health
Publications, 2004.
Maron, Barry J., and Salberg, Lisa. Hypertrophic
Cardiomyopathy: For Patients, Their Families, and
Interested Physicians. Malden, MA: Futura Media
Services, 2001.
Parker, J.M., and Parker, P.M. The Official Patient’s
Sourcebook on Hypertrophic Cardiomyopathy. San
Diego, CA: Icon Health Publications, 2002.
Parker, J.M., and Parker, P.M. The Official Patient’s
Sourcebook on Dilated Cardiomyopathy. San Diego,
CA: Icon Health Publications, 2002.
PERIODICALS

Ommen, Steve R., and Nishimura, Rick A. ‘‘A Physician’s
Guide to the Treatment of Hypertrophic
Cardiomyopathy.’’ HeartViews 1(10): 393 - 401.
<http://www.mayoclinic.org/hypertrophiccardiomyopathy/physiciansguide.html>.
ORGANIZATIONS

American Heart Association, National Center, 7272
Greenville Avenue, Dallas, TX 75231. Telephone: (800)
242-8721; <http://www.americanheart.org/>.
Hypertrophic Cardiomyopathy Association, P.O. Box 306
Hibernia NJ 07842. Telephone: (973) 983-7429;
<http://www.4hcm.org/>.
Children’s Cardiomyopathy Foundation, P.O. Box 547,
Tenafly, New Jersey 07670. Telephone: (201) 227-8852;
<http://www.childrenscardiomyopathy.org/>.
OTHER

Cleveland Clinic Heart Center. <http://www.clevelandclinic.org/heartcenter/pub/guide/disease/hcm.asp>.
National Heart, Blood, and Lung Institute, National
Institutes of Health, NHLBI Health Information Center,
P.O. Box 30105, Bethesda, MD 20824-0105. Telephone:
(301) 592 8573; <http://www.nhlbi.nih.gov>.
Heart Center Online. <http:// www.heartcenteronline.com>.

Judith Sims
737

Cardiomyopathy

KEY TERMS

Cardiopulmonary resuscitation (CPR)

I Cardiopulmonary
resuscitation (CPR)
Definition
Cardiopulmonary resuscitation (CPR) is a procedure to support and maintain breathing and circulation for a person who has stopped breathing
(respiratory arrest) and/or whose heart has stopped
(cardiac arrest).

Purpose
CPR is performed to restore and maintain breathing and circulation and to provide oxygen and blood
flow to the heart, brain, and other vital organs. CPR
should be performed if a person is unconscious and
not breathing. Respiratory and cardiac arrest can be
caused by allergic reactions, an ineffective heartbeat,
asphyxiation, breathing passages that are blocked,
choking, drowning, drug reactions or overdoses, electric shock, exposure to cold, severe shock, or trauma.
CPR can be performed by trained bystanders or
healthcare professionals on infants, children, and
adults. It should always be performed by the person
on the scene who is most experienced in CPR.

Precautions
CPR should never be performed on a healthy
person because it can cause serious injury to a beating
heart by interfering with normal heartbeats.

Description
CPR is part of the emergency cardiac care system
designed to save lives. Many deaths can be prevented
by prompt recognition of the problem and notification
of the emergency medical system (EMS), followed by
early CPR, defibrillation (which delivers a brief electric
shock to the heart in attempt to get the heart to
beat normally), and advanced cardiac life support
measures.
CPR must be performed within four to six minutes after cessation of breathing so as to prevent brain
damage or death. It is a two-part procedure that
involves rescue breathing and external chest compressions. To provide oxygen to a person’s lungs, the
rescuer administers mouth-to-mouth breaths, then
helps circulate blood through the heart to vital organs
by external chest compressions. Mouth-to-mouth
breathing and external chest compression should be
performed together, but if the rescuer is not strong
enough to do both, the external chest compressions
738

should be done. This is more effective than no resuscitation attempt, as is CPR that is performed ‘‘poorly.’’
When performed by a bystander, CPR is designed
to support and maintain breathing and circulation
until emergency medical personnel arrive and take
over. When performed by healthcare personnel, it is
used in conjunction with other basic and advanced life
support measures.
According to the American Heart Association,
early CPR and defibrillation combined with early
advanced emergency care can increase survival rates
for people with a type of abnormal heart beat called
ventricular fibrillation by as much as 40%. CPR by
bystanders may prolong life during deadly ventricular
fibrillation, giving emergency medical service personnel time to arrive.
However, many CPR attempts are not ultimately
successful in restoring a person to a good quality of
life. Often, there is brain damage even if the heart
starts beating again. CPR is therefore not generally
recommended for the chronically or terminally ill or
frail elderly. For these people, it represents a traumatic
and not a peaceful end of life.
Each year, CPR helps save thousands of lives in
the United States. More than five million Americans
annually receive training in CPR through American
Heart Association and American Red Cross courses.
In addition to courses taught by instructors, the
American Heart Association also has an interactive
video called Learning System, which is available at
more than 500 healthcare institutions. Both organizations teach CPR the same way, but use different terms.
These organizations recommend that family members
or other people who live with people who are at risk
for respiratory or cardiac arrest be trained in CPR. A
hand-held device called a CPR Prompt is available to
walk people trained in CPR through the procedure,
using American Heart Association guidelines. CPR
has been practiced for more than 40 years.
Performing CPR
The basic procedure for CPR is the same for all
people, with a few modifications for infants and children
to account for their smaller size.
PERFORMING CPR ON AN ADULT. The first step is
to call the emergency medical system for help by telephoning 911; then to begin CPR, following these steps:


The rescuer opens a person’s airway by placing the
head face up, with the forehead tilted back and the
chin lifted. The rescuer checks again for breathing
(three to five seconds), then begins rescue breathing
GALE ENCYCLOPEDIA OF MEDICINE



After two breaths, the rescuer checks the unconscious person’s pulse by moving the hand that was
under the person’s chin to the artery in the neck
(carotid artery). If the unconscious person has a
heartbeat, the rescuer continues rescue breathing
until help arrives or the person begins breathing
without assistance. If the unconscious person is
breathing, the rescuer turns the person onto his or
her side.



If there is no heartbeat, the rescuer performs chest
compressions. The rescuer kneels next to the unconscious person, placing the heel of one hand in the
spot on the lower chest where the two halves of the
rib cage come together. The rescuer puts one hand on
top of the other on the person’s chest and interlocks
the fingers. The arms are straightened, the rescuer’s
shoulders are positioned directly above the hands on
the unconscious person’s chest. The hands are
pressed down, using only the palms, so that the
person’s breastbone sinks in about 1½–2 inches.
The rescuer releases pressure without removing the
hands, then repeats about 15 times per 10–15 second
intervals.



The rescuer tilts the unconscious person’s head and
returns to rescue breathing for one or two quick
breaths. Then breathing and chest compressions are
alternated for one minute before checking for a
pulse. If the rescuer finds signs of a heartbeat and
breathing, CPR is stopped. If the unconscious person
is breathing but has no pulse, the chest compressions
are continued. If the unconscious person has a pulse
but is not breathing, rescue breathing is continued.



For children over the age of eight, the rescuer performs CPR exactly as for an adult.

PERFORMING CPR ON AN INFANT OR CHILD UNDER
THE AGE OF EIGHT. The procedures outlined above are

followed with these differences:


The rescuer administers CPR for one minute, then
calls for help.



The rescuer makes a seal around the child’s mouth or
infant’s nose and mouth to give gentle breaths. The
rescuer delivers 20 rescue breaths per minute, taking
1½–2 seconds for each breath.

GALE ENCYCLOPEDIA OF MEDICINE



Chest compressions are given with only one hand for
a child and with two or three fingers for an infant.
The breastbone is depressed only 1–1½ inch for a
child and ½–1 inch for an infant, the rescuer gives at
least 100 chest compressions per minute.
New developments in CPR

Some new ways of performing CPR have been
tried. Active compression-decompression resuscitation, abdominal compression done in between chest
compressions, and chest compression using a pneumatic vest have all been tested but none are currently
recommended for routine use.
The active compression-decompression device
was developed to improve blood flow from the heart,
but clinical studies have found no significant difference in survival between standard and active compression-decompression CPR. Interposed abdominal
counterpulsation, which requires two or more rescuers, one compressing the chest and the other compressing the abdomen, was developed to improve
pressure and therefore blood flow. It has been shown
in a small study to improve survival but more data is
needed. A pneumatic vest, which circles the chest of an
unconscious person and compresses it, increases pressure within the chest during external chest compression. The vest has been shown to improve survival in a
preliminary study but more data is necessary for a full
assessment.

Preparation
If a person suddenly becomes unconscious, a rescuer should call out for help from other bystanders,
and then determine if the unconscious person is
responsive by gently shaking the shoulder and shouting a question. Upon receiving no answer, the rescuer
should call the emergency medical system. The rescuer
should check to see whether the unconscious person is
breathing by kneeling near the person’s shoulders,
looking at the person’s chest, and placing a cheek
next to the unconscious person’s mouth. The rescuer
should look for signs of breathing in the chest and
abdomen, and listen and feel for signs of breathing
through the person’s lips. If no signs of breathing are
present after three to five seconds, CPR should be
started.

Aftercare
Emergency medical care is always necessary
after successful CPR. Once a person’s breathing
and heartbeat have been restored, the rescuer should
739

Cardiopulmonary resuscitation (CPR)

(mouth-to-mouth artificial respiration), pinching the
nostrils shut while holding the chin in the other hand.
The rescuer’s mouth is placed against the unconscious person’s mouth with the lips making a tight
seal, then gently exhales for about one to one and a
half seconds. The rescuer breaks away for a moment
and then repeats. The person’s head is repositioned
after each mouth-to-mouth breath.

Cardiopulmonary resuscitation (CPR)

Figure A
Figure D

Figure B

Figure E

Figure C

Figure F

CPR in basic life support. Figure A: The victim should be flat on his back and his mouth should be checked for debris. Figure B: If
the victim is unconscious, open airway, lift neck, and tilt head back. Figure C: If victim is not breathing, begin artificial breathing
with four quick full breaths. Figure D: Check for carotid pulse. Figure E: If pulse is absent, begin artificial circulation by
depressing sternum. Figure F: Mouth-to-mouth resuscitation of an infant. (Illustration by Electronic Illustrators Group.)

740

GALE ENCYCLOPEDIA OF MEDICINE

Cardiac arrest—Temporary or permanent cessation of the heartbeat.
Cardiopulmonary—Relating to the heart and the
lungs.
Defibrillation—A procedure to stop the type of
irregular heart beat called ventricular fibrillation,
usually by using electric shock.
Resuscitation—Bringing a person back to life after
an apparent death or in cases of impending death.
Ventricular fibrillation—An irregular heartbeat
where the heart beats very fast but ineffectively.
Ventricular fibrillation is fatal if not quickly
corrected.

make the person comfortable and stay there until
emergency medical personnel arrive. The rescuer
can continue to reassure the person that help is
coming and talk positively until professionals arrive
and take over.

Risks
CPR can cause injury to a person’s ribs, liver,
lungs, and heart. However, these risks must be
accepted if CPR is necessary to save the person’s life.

Normal results
In many cases, successful CPR results in restoration of consciousness and life. Barring other injuries, a
revived person usually returns to normal functions
within a few hours of being revived.

Abnormal results
These include injuries incurred during CPR and
lack of success with CPR. Possible sites for injuries
include a person’s ribs, liver, lungs, and heart.
Partially successful CPR may result in brain damage.
Unsuccessful CPR results in death.
Resources
BOOKS

Alton, Thygerson. First Aid and CPR. 4th ed. Sudbury,
Massachusetts: Jones & Bartlett Pub, 2001.
Knoop, Kevin J., and Lawrence B. Stack. Atlas of
Emergency Medicine. 2nd ed. New York: McGraw Hill,
2001.

GALE ENCYCLOPEDIA OF MEDICINE

National Safety Council. First Aid and CPR for Infants and
Children. 4th ed. Sudbury, Massachusetts: Jones &
Bartlett Pub, 2001.
PERIODICALS

Davies, N., and D. Gould. ‘‘Updating cardiopulmonary
resuscitation skills: a study to examine the efficacy of
self-instruction on nurses’ competence.’’ Journal of
Clinical Nursing 9 (2000): 400-410.
Eftestol T., K. Sunde, S. O. Aase, J. H. Husoy, and
P. A. Steen. ‘‘‘Probability of successful defibrillation’
as a monitor during CPR in out-of-hospital
cardiac arrested patients.’’ Resuscitation 48 (2001):
245-254.
Kern, K. B., H. R. Halperin, and J. Field. ‘‘New
guidelines for cardiopulmonary resuscitation and
emergency cardiac care: changes in the management
of cardiac arrest.’’ Journal of the American Medical
Association 285 (2001): 1267-1269.
Meyer W., and F. Balck. ‘‘Resuscitation decision index: a
new approach to decision-making in prehospital CPR.’’
Resuscitation 48 (2001): 255-263.
ORGANIZATIONS

American College of Emergency Physicians. P.O. Box
619911, Dallas, TX 75261-9911. (800) 798-1822 or
(972) 550-0911. Fax: (972) 580-2816. <http://www.
acep.org/>. info@acep.org.
American College of Osteopathic Emergency Physicians.
142 E. Ontario Street, Suite 550, Chicago, IL 60611.
(312) 587-3709 or (800) 521-3709. Fax: (312) 587-9951.
<http://www.acoep.org>.
American Heart Association, National Center. 7272
Greenville Avenue, Dallas, TX 75231. (877) 242-4277.
<http://www.americanheart.org/
Heart_and_Stroke_A_Z_Guide/heim.html>.
Heimlich Institute. PO Box 8858, Cincinnati, OH 45208.
<http://www.heimlichinstitute.org/index.htm>.
heimlich@iglou.com.
National Safe Kids Campaign. 1301 Pennsylvania Avenue,
Suite 1000, Washington, DC 20004-1707. <http://
pedsccm.wustl.edu/All-Net/english/neurpage/protect/
drown.htm>.
OTHER

American Heart Association. <http://www.cpr-ecc.org/>
and <http://www.americanheart.org/
Heart_and_Stroke_A_Z_Guide/cprs.html>.
Columbia Presbyterian Medical Center. <http://cpmcnet.
columbia.edu/texts/guide/hmg13_0001.html>.
Learn CPR. <http://www.learn-cpr.com>.
National Registry of Cardiopulmonary Resuscitation.
<http://www.nrcpr.org/>.
University of Washington School of Medicine. <http://
depts.washington.edu/learncpr/>.

L. Fleming Fallon, Jr., MD, DrPH
741

Cardiopulmonary resuscitation (CPR)

KEY TERMS

Cardioversion

I Cardioversion
Definition
Cardioversion refers to the process of restoring
the heart’s normal rhythm by applying a controlled
electric shock to the exterior of the chest.

Purpose
When the heart beats too fast, blood no longer
circulates effectively in the body. Cardioversion
is used to stop this abnormal beating so that the
heart can begin normal rhythm and pump more
efficiently.

KEY TERMS
Atrial fibrillation—A condition in which the upper
chamber of the heart quivers instead of pumping in
an organized way.
Atrial flutter—A rapid pulsation of the upper
chamber of the heart that interferes with normal
function.
Ventricular fibrillation—A condition in which the
lower chamber of the heart quivers instead of
pumping in an organized way.
Ventricular tachycardia—A rapid heart beat,
usually over 100 beats per minute.

Precautions
Not all unusual heart rhythms (called arrhythmias) are dangerous or fatal. Atrial fibrillation and
atrial flutter often revert to normal rhythms without
the need for cardioversion. Healthcare providers may
also try to correct the heart rhythm with medication or
recommend a lifestyle change before trying cardioversion. However, ventricular tachycardia lasting more
than 30 seconds and ventricular fibrillation require
immediate cardioversion.

Description
Elective cardioversion is usually scheduled ahead
of time. After arriving at the hospital, an intravenous
(IV) catheter will be placed in the arm and oxygen will
be given through a face mask. A short-acting general
anesthetic will be administered through the vein.
During the two or three minutes of anesthesia, the
doctor will apply two paddles to the exterior of the
chest and administer the electric shock. It may be
necessary to give the shock two or three times to
obtain normal rhythm.

Preparation
Medication to thin the blood is usually given for
at least three weeks before elective cardioversion.
Food intake should be stopped eight hours before
the procedure.

Aftercare
Medical personnel will monitor the heart rhythm
for a few hours, after which the patient is usually sent
home. It is advisable to arrange for transportation
home, because drowsiness may last several hours.
742

The doctor may prescribe anti-arrhythmic medication
to prevent the abnormal rhythm from returning.

Risks
Cardioverters have been in use for many years
and the risks are few. Those unlikely risks that
remain include those instances when the device delivers greater or lesser power than expected or when
power setting and control knobs are not set correctly.
Unfortunately, in a number of cases, the heart prefers
its abnormal rhythm and reverts to it despite
cardioversion.

Normal results
Most cardioversions are successful and, at least
for a time, restore the normal heart rhythm.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave.
Dallas, TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dorothy Elinor Stonely

Carisoprodol see Muscle relaxants
Carotid artery surgery see Endarterectomy
Carotid Doppler ultrasound see Doppler
ultrasonography
Carotid endarterectomy see Endarterectomy
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Carotid sinus massage involves rubbing the large
part of the arterial wall at the point where the common
carotid artery, located in the neck, divides into its two
main branches.

Purpose
Sinus, in this case, means an area in a blood vessel
that is bigger than the rest of the vessel. This is a
normal dilation of the vessel. Located in the neck
just below the angle of the jaw, the carotid sinus sits
above the point where the carotid artery divides into
its two main branches. Rubbing the carotid sinus stimulates an area in the artery wall that contains nerve
endings. These nerves respond to changes in blood
pressure and are capable of slowing the heart rate.
The response to this simple procedure often slows a
rapid heart rate (for example, atrial flutter or atrial
tachycardia) and can provide important diagnostic
information to the physician.

Description
The patient will be asked to lie down, with the
neck fully extended and the head turned away from the
side being massaged. While watching an electrocardiogram monitor, the doctor will gently touch the carotid
sinus. If there is no change in the heart rate on the
monitor, the pressure is applied more firmly with a
gentle rotating motion. After massaging one side of
the neck, the massage will be repeated on the other
side. Both sides of the neck are never massaged at the
same time.

KEY TERMS
Angina pectoris—Chest pain usually caused by a
lack of oxygen in the heart muscle.
Arrhythmia—Any deviation from a normal heart
beat.
Atrial fibrillation—A condition in which the upper
chamber of the heart quivers instead of pumping in
an organized way.
Atrial flutter—Rapid, inefficient contraction of the
upper chamber of the heart.
Carotid artery—One of the major arteries supplying blood to the head and neck.
Tachycardia—A rapid heart beat, usually over 100
beats per minute.

Normal results
Carotid sinus massage will slow the heart rate
during episodes of atrial flutter, fibrillation, and
some tachycardias. It has been known to stop the
arrhythmia completely. If the procedure is being
done to help diagnose angina pectoris, massaging the
carotid sinus may make the discomfort go away.
Resources
BOOKS

McGood, Michael D., editor. Mayo Clinic Heart Book: The
Ultimate Guide to Heart Health. New York: William
Morrow and Co., Inc., 1993.

Dorothy Elinor Stonely

Preparation
No special preparation is needed for carotid sinus
massage.

Aftercare
No aftercare is required.

I Carpal tunnel syndrome
Definition
Carpal tunnel syndrome is a disorder caused by
compression at the wrist of the median nerve supplying the hand, causing numbness and tingling.

Risks
The physician must be sure there is no evidence of
blockage in the carotid artery before performing the
procedure. Massage in a blocked area might cause a
clot to break loose and cause a stroke.
GALE ENCYCLOPEDIA OF MEDICINE

Description
The carpal tunnel is an area in the wrist where the
bones and ligaments create a small passageway for
the median nerve. The median nerve is responsible
743

Carpal tunnel syndrome

I Carotid sinus massage

Carpal tunnel syndrome

for both sensation and movement in the hand, in
particular the thumb and first three fingers. When
the median nerve is compressed, an individual’s hand
will feel as if it has ‘‘gone to sleep.’’
Women between the ages of 30 and 60 have the
highest rates of carpal tunnel syndrome. Research has
demonstrated that carpal tunnel syndrome is a very
significant cause of missed work days due to pain. In
1995, about $270 million was spent on sick days taken
for pain from repetitive motion injuries.

Carpal tunnel ligament

Median nerve

Carpal tunnel ligament (severed)

Causes and symptoms
Compression of the median nerve in the wrist can
occur during a number of different conditions, particularly those conditions which lead to changes in
fluid accumulation throughout the body. Because
the area of the wrist through which the median
nerve passes is very narrow, any swelling in the area
will lead to pressure on the median nerve. This pressure will ultimately interfere with the nerve’s ability
to function normally. Pregnancy, obesity, arthritis,
certain thyroid conditions, diabetes, and certain
pituitary abnormalities all predispose to carpal tunnel syndrome. Other conditions which increase
the risk for carpal tunnel syndrome include some
forms of arthritis and various injuries to the arm
and wrist (including fractures, sprains, and dislocations). Furthermore, activities which cause an individual to repeatedly bend the wrist inward toward the
forearm can predispose to carpal tunnel syndrome.
Certain jobs which require repeated strong wrist
motions carry a relatively high risk of carpal tunnel
syndrome. Injuries of this type are referred to as
‘‘repetitive motion’’ injuries, and are more frequent
among secretaries doing a lot of typing, people working at computer keyboards or cash registers, factory
workers, and some musicians.
Symptoms of carpal tunnel syndrome include
numbness, burning, tingling, and a prickly pin-like
sensation over the palm surface of the hand, and
into the thumb, forefinger, middle finger, and half
of the ring finger. Some individuals notice a shooting
pain which goes from the wrist up the arm, or down
into the hand and fingers. With continued median
nerve compression, an individual may begin to
experience muscle weakness, making it difficult to
open jars and hold objects with the affected hand.
Eventually, the muscles of the hand served by the
median nerve may begin to grow noticeably smaller
(atrophy), especially the fleshy part of the thumb.
Untreated, carpal tunnel syndrome may eventually
744

Median nerve

The most severe cases of carpal tunnel syndrome may
require surgery to decrease the compression of the median
nerve and restore its normal function. This procedure
involves severing the ligament that crosses the wrist, thus
allowing the median nerve more room and decreasing compression. (Illustration by Electronic Illustrators Group.)

result in permanent weakness, loss of sensation, or
even paralysis of the thumb and fingers of the affected
hand.

Diagnosis
The diagnosis of carpal tunnel syndrome is made
in part by checking to see whether the patient’s
symptoms can be brought on by holding his or her
hand in position with wrist bent for about a minute.
Wrist x rays are often taken to rule out the possibility of a tumor causing pressure on the median nerve.
A physician examining a patient suspected of having
carpal tunnel syndrome will perform a variety of
simple tests to measure muscle strength and sensation in the affected hand and arm. Further testing
might include electromyographic or nerve conduction velocity testing to determine the exact severity
of nerve damage. These tests involve stimulating the
median nerve with electricity and measuring the
resulting speed and strength of the muscle response,
as well as recording speed of nerve transmission
across the carpal tunnel.
GALE ENCYCLOPEDIA OF MEDICINE

Carpal tunnel—A passageway in the wrist, created
by the bones and ligaments of the wrist, through
which the median nerve passes.
Electromyography—A type of test in which a
nerve’s function is tested by stimulating a nerve
with electricity, and then measuring the speed
and strength of the corresponding muscle’s
response.
Median nerve—A nerve which runs through the
wrist and into the hand. It provides sensation
and some movement to the hand, the thumb, the
index finger, the middle finger, and half of the ring
finger.

disability in the affected hand. Most people are able to
control the symptoms of carpal tunnel syndrome with
splinting and anti-inflammatory agents. For those
who go on to require surgery, about 95% will have
complete cessation of symptoms.

Prevention
Prevention is generally aimed at becoming aware
of the repetitive motions which one must make which
could put the wrist into a bent position. People who
must work long hours at a computer keyboard, for
example, may need to take advantage of recent
advances in ‘‘ergonomics,’’ which try to position the
keyboard and computer components in a way that
increases efficiency and decreases stress. Early use of
a splint may also be helpful for people whose jobs
increase the risk of carpal tunnel syndrome.
Resources

Treatment
Carpal tunnel syndrome is initially treated with
splints, which support the wrist and prevent it from
flexing inward into the position which exacerbates median nerve compression. Some people get significant
relief by wearing such splints to sleep at night, while
others will need to wear the splints all day, especially if
they are performing jobs which stress the wrist.
Ibuprofen or other nonsteroidal anti-inflammatory
drugs may be prescribed to decrease pain and swelling.
When carpal tunnel syndrome is more advanced, injection of steroids into the wrist to decrease inflammation
may be necessary.
The most severe cases of carpal tunnel syndrome
may require surgery to decrease the compression of the
median nerve and restore its normal function. Such a
repair involves cutting that ligament which crosses the
wrist, thus allowing the median nerve more room and
decreasing compression. This surgery is done almost
exclusively on an outpatient basis and is often performed without the patient having to be made unconscious. Careful injection of numbing medicines (local
anesthesia) or nerve blocks (the injection of anesthetics
directly into the nerve) create sufficient numbness to
allow the surgery to be performed painlessly, without
the risks associated with general anesthesia. Recovery
from this type of surgery is usually quick and without
complications.

Prognosis
Without treatment, continued pressure on the
median nerve puts an individual at risk for permanent
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Seiler, John Gray. ‘‘Carpal Tunnel Syndrome: Update on
Diagnostic Testing and Treatment Options.’’
Consultant 37, no. 5 (May 1997): 1233.

Rosalyn Carson-DeWitt, MD

Casts see Immobilization
Cat-bite infection see Animal bite infections

I Cat-scratch disease
Definition
Cat-scratch disease is an uncommon infection
that typically results from a cat’s scratch or bite.
Most sufferers experience only moderate discomfort
and find that their symptoms clear up without
any lasting harm after a few weeks or months.
Professional medical treatment is rarely needed.

Description
Cat-scratch disease (also called cat-scratch fever)
is caused by the Bartonella henselae bacterium, which
is found in cats around the world and is transmitted
from cat to cat by fleas. Researchers have discovered
that large numbers of North American cats carry
antibodies for the disease (meaning that the cats
have been infected at some point in their lives).
Some parts of North America have much higher
745

Cat-scratch disease

KEY TERMS

Cat-scratch disease

rates of cat infection than others, however. Bartonella
henselae is uncommon or absent in cold climates,
which fleas have difficulty tolerating, but prevalent
in warm, humid places such as Memphis, Tennessee,
where antibodies were found in 71% of the cats
tested. The bacterium, which remains in a cat’s
bloodstream for several months after infection,
seems to be harmless to most cats, and normally an
infected cat will not display any symptoms. Kittens
(cats less than one year old) are more likely than adult
cats to be carrying the infection.
Bartonella henselae can infect people who are
scratched or (more rarely) bitten or licked by a cat. It
cannot be passed from person to person. Although
cats are popular pets found in about 30% of
American households, human infection appears to be
rare. One study estimated that for every 100,000
Americans there are only 2.5 cases of cat-scratch disease each year (2.5/100,000). It is also unusual for
more than one family member to become ill; a
Florida investigation discovered multiple cases in
only 3.5% of the families studied. Children and teenagers appear to be the most likely victims of catscratch disease, although the possibility exists that
the disease may be more common among adults than
previously thought.

Causes and symptoms
The first sign of cat-scratch disease may be a small
blister at the site of a scratch or bite three to 10 days
after injury. The blister (which sometimes contains
pus) often looks like an insect bite and is usually
found on the hands, arms, or head. Within two
weeks of the blister’s appearance, lymph nodes near
the site of injury become swollen. Often the infected
person develops a fever or experiences fatigue or headaches. The symptoms usually disappear within a
month, although the lymph nodes may remain swollen
for several months. Hepatitis, pneumonia, and other
dangerous complications can arise, but the likelihood
of cat-scratch disease posing a serious threat to health
is very small. AIDS patients and other immunocompromised people face the greatest risk of dangerous
complications.
Occasionally, the symptoms of cat-scratch disease
take the form of what is called Parinaud’s oculoglandular syndrome. In such cases, a small sore develops
on the palpebral conjunctiva (the membrane lining
the inner eyelid), and is often accompanied by conjunctivitis (inflammation of the membrane) and swollen lymph nodes in front of the ear. Researchers
suspect that the first step in the development of
746

Parinaud’s oculoglandular syndrome occurs when
Bartonella henselae bacteria pass from a cat’s saliva
to its fur during grooming. Rubbing one’s eyes after
handling the cat then transmits the bacteria to the
conjunctiva.

Diagnosis
A family doctor should be called whenever a cat
scratch or bite fails to heal normally or is followed by a
persistent fever or other unusual symptoms such as
long-lasting bone or joint pain. The appearance of
painful and swollen lymph nodes is another reason
for consulting a doctor. When cat-scratch disease is
suspected, the doctor will ask about a history of exposure to cats and look for evidence of a cat scratch or
bite and swollen lymph nodes. A blood test for
Bartonella henselae may be ordered to confirm the
doctor’s diagnosis.

Treatment
For otherwise healthy people, rest and over-thecounter medications for reducing fever and discomfort
(such as acetaminophen) while waiting for the disease
to run its course are usually all that is necessary.
Antibiotics are prescribed in some cases, particularly
when complications occur or the lymph nodes remain
swollen and painful for more than two or three
months, but there is no agreement among doctors
about when and how they should be used. If a lymph
node becomes very swollen and painful, the family
doctor may decide to drain it.

Prognosis
Most people recover completely from a bout of
cat-scratch disease. Further attacks are rare.

Prevention
Certain common–sense precautions can be taken
to guard against the disease. Scratches and bites
should be washed immediately with soap and water,
and it is never a good idea to rub one’s eyes after
handling a cat without first washing one’s hands.
Children should be told not to play with stray cats or
make cats angry. Immunocompromised people should
avoid owning kittens, which are more likely than adult
cats to be infectious. Because cat-scratch disease is
usually not a life-threatening illness and people tend
to form strong emotional bonds with their cats, doctors do not recommend getting rid of a cat suspected of
carrying the disease.
GALE ENCYCLOPEDIA OF MEDICINE

Acetaminophen—A drug for relieving pain and fever.
AIDS—Acquired immunodeficiency syndrome.
A disease that attacks the immune system.
Antibiotics—A category of manufactured substances used to combat infection.
Antibodies—Special substances created by the
body to combat infection.
Bacterium—A tiny organism. Some bacteria cause
disease.
Hepatitis—A disease that inflames the liver.
Immune system—A body system that combats
disease.
Immunocompromised—Having a damaged immune system.
Lymph nodes—Small, kidney-shaped organs that
filter a fluid called lymph.
Pneumonia—A disease that inflames the lungs.
Pus—A thick yellowish or greenish fluid.

Resources
PERIODICALS

Smith, David L. ‘‘Cat-Scratch Disease and Related Clinical
Syndromes.’’ American Family Physician April 1997:
1783.

Howard Baker

Cat-scratch fever see Cat-scratch disease
CAT scan see Computed tomography scans

I Cataract surgery
Definition
Cataract surgery is a procedure performed to
remove a cloudy lens from the eye; usually an intraocular lens is implanted at the same time.

Purpose
The purpose of cataract surgery is to restore clear
vision. It is indicated when cloudy vision due to cataracts has progressed to such an extent that it interferes
with normal daily activities. It is one of the most
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Cataract surgery is not performed on both eyes at
once. To avoid risking blindness in both eyes in the
event of infection or other catastrophe, the first eye is
allowed to heal before the cataract is removed from
the second eye.
The presence of cataracts can mask additional eye
problems, such as retinal damage, that neither doctors
nor patients are aware of prior to surgery. Since such
conditions will continue to impair sight after cataract
removal if they are not identified and treated, the
eventual outcome of cataract surgery will depend on
the outcome of other problems.
In 1997 and 1998, evidence that cataract surgery
can contribute to the progression of age-related macular degeneration (ARMD) was published. ARMD is
the degeneration of the central part of the retina.
Accordingly, ARMD patients with cataracts must
weigh the risks of the loss of central vision, within
four or five years, against short-term improvement.
When an ARMD patient chooses cataract surgery,
the surgeon should shield the retina against bright
light to protect it from possible light-induced damage
during surgery and install an intraocular lens capable
of absorbing ultraviolet and blue light, which seem to
do the most damage.

Description
There are two types of cataract surgery: intracapsular and extracapsular. Intracapsular surgery is the
removal of both the lens and the thin capsule that
surround the lens. This type of surgery was common
before 1980, but has since been displaced by extracapsular surgery. Removal of the capsule requires a large
incision and doesn’t allow comfortable intraocular
lens implantation. Thus, people who undergo intracapsular cataract surgery have long recovery periods
and have to wear very thick glasses.
Extracapsular cataract surgery is the removal of
the lens where the capsule is left in place. Each year in
the United States, over a million cataracts are removed
this way. Physicians and researchers continue to
improve cataract surgery methods. Research from
France in 2003 said that cataract removal and nonpenetrating glaucoma surgery can be combined in
glaucoma patients.
There are two methods for extracapsular cataract
surgery. The usual technique is phacoemulsification.
747

Cataract surgery

commonly performed surgical procedures in the
world.

KEY TERMS

Cataract surgery
Cataract surgery in progress. (Photograph by David Sutton/Zuma Images, The Stock Market. Reproduced by permission.)

A tiny incision (about 0.12in or 3 mm long) is made
next to the cornea (the eye’s outer covering), and an
ultrasonic probe is used to break the cataract into
minute pieces, which are then removed by suction.
When the lens is too hard to be emulsified ultrasonically, the surgeon will use a different extracapsular
technique requiring a larger incision. An incision
about 0.37 in (9 mm) inches long is made, and the
whole lens (without its capsule) is removed through
the incision. Both kinds of extracapsular extraction
leave the back of the capsule intact, so a silicone or
plastic intraocular lens can be stably implanted in
about the same location as the original lens.
The surgery takes about 30–60 minutes per eye.

Preparation
Patients must have a pre-operation eye examination, which will include ultrasound analysis to make
sure the retina (the innermost layer of the eye, containing the light receptors) is intact and also to measure
eye curvature so that a lens with the proper correction
can be implanted. The patient also will have a preoperative physical examination. In addition, patients
748

start a course of antibiotic eye drops or ointment the
day before surgery.

Aftercare
Proper post-operative care is especially important after cataract surgery. Patients will need someone to drive them home after the surgery and should
not bend over or do anything strenuous for about two
weeks. They should refrain from rubbing the eye,
should wear glasses to protect their eye, and should
wear a shield while sleeping so the eye won’t be
rubbed or bumped accidentally. The patient will
usually continue their antibiotic for two to three
weeks and will also take anti-inflammatory medication for about the same length of time. If the patient
experiences inflammation, redness, or pain, they
should seek immediate medical treatment to avoid
serious complications.

Risks
Cataract surgery itself is quite safe; over 90% of the
time, there are no complications. Possible complications
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Age-related macular degeneration (ARMD)—
Degeneration of the macula (the central part of
the retina where the rods and cones are most
dense) that leads to loss of central vision in people
over 60.
Cataract—Progressive opacity or clouding of an
eye lens, which obstructs the passage of light to
the retina.
Cornea—Clear outer covering of the front of
the eye.
Intraocular lens—Lens made of silicone or plastic
placed within the eye; can be corrective.
Retina—Innermost layer at the back of the eye,
which contains light receptors, the rods and cones.

include intraocular infection (endophthalmitis), central
retinal inflammation (macular edema), post-operative
glaucoma, retinal detachment, bleeding under the retina
(choroidal hemorrhage), and tiny lens fragments in the
back (vitreous) cavity of the eye, all of which can lead to
loss of sight. Since increased use of the phacoemulsification method of cataract surgery, researchers have noted
a decline in cases of infection (endophthalmitis). This
probably is because injectable intraocular lenses do not
make contact with the ocular surface. In 2004, the FDA
approved a new capsular tension ring for use in cataract
surgery that helps prevent lens dislocation and other
possible complications of surgery.

Normal results
Ordinarily, patients experience improved visual
acuity and improved perception of the vividness of
colors, leading to increased abilities in many activities,
including reading, needlework, driving, golf, and tennis, for example. In addition, sometimes implanted
corrective lenses eliminate the need for eyeglasses
or contact lenses. Researchers and manufacturers
also continue to work to improve the lenses available
in cataract surgeries, so that eventual vision and outcome are improved.
Resources
PERIODICALS

‘‘Cataract Removal, Nonpenetrating Glaucoma Surgery
Can Be Combined.’’ Biotech Week September 13,
2003: 133.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Society of Cataract and Refractive Surgery. 4000
Legato Road, Suite 850, Fairfax, VA 22033-4055. (703)
591-2220. <http://www.ascrs.org>.
OTHER

‘‘Cataract in Adults: A Patient’s Guide.’’ National Library of
Medicine Page. <http://text.nlm.nih.gov>.
‘‘Patient Information.’’ Digital Journal of Ophthalmology.
<http://www.djo.harvard.edu/meei/PI/
PIhome.html>.

Lorraine Lica, PhD
Teresa G. Odle

I Cataracts
Definition
A cataract is a cloudiness or opacity in the normally transparent crystalline lens of the eye. This
cloudiness can cause a decrease in vision and may
lead to eventual blindness.

Description
The human eye has several parts. The outer layer
of the eyeball consists of a transparent dome-shaped
cornea and an opaque, white sclera. The cornea and
sclera help protect the eye. The next layer includes the
iris, pupil, and ciliary body. The iris is the colored part
of the eye and the pupil is the small dark round hole in
the middle of the iris. The pupil and iris allow light
into the eye. The ciliary body contains muscles that
help in the eye’s focusing ability. The lens lies behind
the pupil and iris. It is covered by a cellophane-like
capsule. The lens is normally transparent, elliptical in
shape, and somewhat elastic. This elasticity allows the
lens to focus on both near and far objects. The lens is
749

Cataracts

KEY TERMS

‘‘FDA Approves Stabil Eyes Capsular Tension Rig for
Cataract Surgery.’’ Biotech Week May 26, 2004: 23.
Groves, Nancy. ‘‘Advances in Cataract Surgery Driven by
Technology; Surgeons Able to Achieve Better
Outcomes With New IOL, Viscoadaptive Devices.’’
Ophthalmology Times April 1, 2004: 39.
Mayer, E., et al. ‘‘A 10-year Retrospective Survey of
Cataract Surgery and Endophthalmitis in a Single Yey
Unit: Injectable Lenses Lower the Incidence of
Endophthalmitis.’’ British Journal of Ophthalmology
July 2003: 867–873.

Cataracts

attached to the ciliary body by fibers (zonules of Zinn).
Muscles in the ciliary body act on the zonules, which
then change the shape of the lens. This process is called
accommodation—the lens focuses images to help
make vision clear. As people age, the lens hardens
and changes shape less easily. As a result, the accommodation process becomes more difficult, making it
harder to see things up close. This generally occurs
around the age of 40 and continues until about age 65.
The condition is called presbyopia. It is a normal condition of aging, generally resulting in the need for
reading glasses.
The lens is made up of approximately 35% protein
and 65% water. As people age, degenerative changes
in the lens’s proteins occur. Changes in the proteins,
water content, enzymes, and other chemicals are some
of the reasons for the formation of a cataract.
The major areas of the lens are the nucleus, the
cortex, and the capsule. The nucleus is in the center of
the lens, the cortex surrounds the nucleus, and the
capsule is the outer layer. Opacities can occur in any
area of the lens. Cataracts, then, can be classified
according to location (nuclear, cortical, or posterior
subcapular cataracts). The density and location of the
cataract determine the amount of vision affected. If
the cataract forms in the area of the lens directly
behind the pupil, vision may be significantly impaired.
A cataract that occurs on the outer edges or side of the
lens will create less of a visual problem.
Cataracts in the elderly are so common that they
are thought to be a normal part of the aging process.
Between the ages of 52 and 64, there is a 50% chance of
having a cataract, while at least 70% of those 70 and
older are affected. In 2004, it was revealed that blacks
are twice as likely to develop cataracts as whites.
Cataracts associated with aging (senile or age-related
cataracts) most often occur in both eyes, with
each cataract progressing at a different rate. Initially,
cataracts may not affect vision. If the cataract remains
small or at the periphery of the lens, the visual changes
may be minor.
Cataracts that occur in people other than the
elderly are much less common. Congenital cataracts
occur very rarely in newborns. Genetic defects or an
infection or disease in the mother during pregnancy are
among the causes of congenital cataracts. Traumatic
cataracts may develop after a foreign body or trauma
injures the lens or eye. Systemic illnesses, such as
diabetes, may result in cataracts. Cataracts can also
occur secondary to other eye diseases—for example,
an inflammation of the inner layer of the eye (uveitis)
or glaucoma. Such cataracts are called complicated
750

cataracts. Toxic cataracts result from chemical toxicity, such as steroid use. Cataracts can also result from
exposure to the sun’s ultraviolet (UV) rays.

Causes and symptoms
Recent studies have been conducted to try to
determine whether diet or the use of vitamins might
have an effect on the formation of cataracts in older
people. The results have been mixed, with some studies
finding a connection and other studies finding none.
Much interest has been focused on the use of antioxidant supplements as a protection against cataracts.
Antioxidant vitamins such as vitamins A, C, E and
beta-carotene help the body clean-up oxygen-free
radicals. Some vitamins are marketed specifically for
the eyes. Patients should speak to their doctors about
the use of such vitamins.
Smoking and alcohol intake have been implicated
in cataract formation. Some studies have determined
that a diet high in fat will increase the likelihood of
cataract formation, while an increase in foods rich in
antioxidants will reduce the incidence. More research
is needed to determine if diet, smoking, alcohol consumption, or vitamins have any connection to the
formation of cataracts.
There are several common symptoms of cataracts:


gradual, painless onset of blurry, filmy, or fuzzy
vision



poor central vision



frequent changes in eyeglass prescription



changes in color vision



increased glare from lights, especially oncoming
headlights when driving at night



‘‘second sight’’ improvement in near vision (no
longer needing reading glasses), but a decrease in
distance vision



poor vision in sunlight



presence of a milky whiteness in the pupil as the
cataract progresses.

Diagnosis
Both ophthalmologists and optometrists may
detect and monitor cataract growth and prescribe
prescription lenses for visual deficits. However, only
an ophthalmologist can perform cataract extraction.
Cataracts are easily diagnosed from the reporting
of symptoms, a visual acuity exam using an eye chart,
and by examination of the eye itself. Shining a penlight
GALE ENCYCLOPEDIA OF MEDICINE

A dense cataract on lens of eye. (Photograph by Margaret
Cubberly, Phototake NYC. Reproduced by permission.)

into the pupil may reveal opacities or a color change of
the lens even before visual symptoms have developed.
An instrument called a slit lamp is basically a large
microscope. This lets the doctor examine the front of
the eye and the lens. The slit lamp helps the doctor
determine the location of the cataract.
Some other diagnostic tests may be used to determine if cataracts are present or how well the patient
may potentially see after surgery. These include a
glare test, potential vision test, and contrast sensitivity test.

Treatment
For cataracts that cause no symptoms or only
minor visual changes, no treatment may be necessary.
Continued monitoring and assessment of the cataract
is needed by an ophthalmologist or optometrist at
scheduled office visits. Increased strength in prescription eyeglasses or contact lenses may be helpful. This
may be all that is required if the cataract does not
reduce the patient’s quality of life.
Cataract surgery—the only option for patients
whose cataracts interfere with vision to the extent of
affecting their daily lives—is the most frequently performed surgery in the United States. It generally
improves vision in over 90% of patients. Some people
have heard that a cataract should be ‘‘ripe’’ before
being removed. A cataract is considered ripe or
mature when the lens is completely opaque. Most
cataracts are removed before they reach this stage.
Sometimes cataracts need to be removed so that the
doctor can examine the back of the eye more carefully. This is important in patients with diseases that
may affect the eye. If cataracts are present in both
GALE ENCYCLOPEDIA OF MEDICINE

Surgery to remove cataracts is generally an outpatient procedure. A local anesthetic is used and
the procedure lasts about one hour. Removal of
the cloudy lens can be done by several different
procedures. The three types of cataract surgery available are:


Extracapsular cataract extraction. This type of cataract extraction is the most common. The lens and
the front portion of the capsule are removed. The
back part of the capsule remains, providing strength
to the eye.



Intracapsular cataract extraction. The lens and the
entire capsule are removed. This method carries an
increased risk for detachment of the retina and swelling after surgery. It is rarely used.



Phacoemulsification. This type of extracapsular
extraction needs a very small incision, resulting in
faster healing. Ultrasonic vibration is applied to the
lens to break it up into very small pieces which are then
aspirated out of the eye with suction by the ophthalmologist. A new liquid technique that its inventor says
may one day replace ultrasound has been invented,
but has not yet been proven in clinical trials.

A replacement lens is usually inserted at the time
of the surgery. A plastic artificial lens called an intraocular lens (IOL) is placed in the remaining posterior
lens capsule of the eye. When the intracapsular extraction method is used, an IOL may be clipped onto the
iris. Contact lenses and cataract glasses (aphakic
lenses) are prescribed if an IOL was not inserted. A
folding IOL is used when phacoemulsification is performed to accommodate the small incision.
Antibiotic drops to prevent infection and steroids
to reduce inflammation are prescribed after surgery.
An eye shield or glasses during the day will protect the
eye from injury while it heals. During the night, an eye
shield is worn. The patient returns to the doctor the
day after surgery for assessment, with several followup visits over the next two months to monitor the
healing process.
751

Cataracts

---

eyes, only one eye at a time should be operated on.
Healing occurs in the first eye before the second
cataract is removed, sometimes as early as the following week. A final eyeglass prescription is usually
given about four to six weeks after surgery. Patients
will still need reading glasses. The overall health of
the patient needs to be considered in making the
decision to operate. However, age alone need not
preclude effective surgical treatment of cataracts.
People in their nineties can have successful return of
vision after cataract surgery.

Catatonia

KEY TERMS
Aphakia—Absence of the lens of the eye.
Ciliary body—A structure in the eye that contains
muscles that will affect the focusing of the lens.
Glaucoma—Disease of the eye characterized by
increased pressure of the fluid inside the eye.
Untreated, glaucoma can lead to blindness.
Phacoemulsification—Surgical proceduretoremove
a cataract using sound waves to disintegrate the lens
which is then removed by suction.
Retina—The innermost layer of the eyeball. Images
focused onto the retina are then sent to the brain.
Ultraviolet radiation (UV)—Invisible light rays
that may be responsible for sunburns, skin cancers,
and cataract formation.
Uveitis—Inflammation of the uvea. The uvea is a
continuous layer of tissue that consists of the iris,
the ciliary body, and the choroid. The uvea lies
between the retina and sclera.

Prognosis
The success rate of cataract extraction is very
high, with a good prognosis. A visual acuity of 20/40
or better may be achieved. If an extracapsular cataract
extraction was performed, a secondary cataract may
develop in the remaining back portion of the capsule.
This can occur one to two years after surgery. YAG
capsulotomy is most often used for this type of cataract. YAG stands for yttrium aluminum garnet, the
name of the laser used for this procedure. This is a
painless outpatient procedure and requires no incision. The laser beam makes a small opening in the
remaining back part of the capsule, allowing light
through.
In a very small percentage (3–5%) of surgical
cataract extractions, complications occur. Infections,
swelling of the cornea (edema), bleeding, retinal
detachment, and the onset of glaucoma have been
reported. Some problems may occur one to two days,
or even several weeks, after surgery. Any haziness,
redness, decrease in vision, nausea, or pain should be
reported to the surgeon immediately.

Prevention
Preventive measures emphasize protecting the
eyes from UV radiation by wearing glasses with
a special coating to protect against UV rays. Dark
752

lenses alone are not sufficient. The lenses must
protect against UV light (specifically, UV-A and
UV-B). Antioxidants may also provide some protection by reducing free radicals that can damage lens
proteins. A healthy diet rich in sources of antioxidants,
including citrus fruits, sweet potatoes, carrots, green
leafy vegetables, and/or vitamin supplements may
be helpful. In 2004, research in England revealed
that nonsteroidal anti-inflammatory drugs (over-the
counter pain killers such as aspirin) may help decrease
risk of cataracts by as much as 43%. When taking
certain medications, such as steroids, more frequent
eye exams may be necessary. Patients should speak
to their doctors to see if medications may affect
their eyes.
Resources
PERIODICALS

‘‘Blacks May Have Higher Incidence of Cataract.’’ Review of
Optometry April 15, 2004: 12.
‘‘Research Suggests Aspirin Helps Combat Cataracts.’’
Health & Medicine Week June 21, 2004: 724.
Talsma, Julia. ‘‘Liquefication Device Provides Safe
Removal of All Cataracts: Lens Emulsified with BSS
Micropulses Using Reusable Titanium Handpiece With
Smooth Polymer Tip.’’ Ophthlamology Times June 1,
2004: 50.
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
The Lighthouse. 111 East 59th St., New York, NY 10022.
(800) 334-5497. <http://www.lighthouse.org>.
Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://
www.preventblindness.org>.

Cynthia L. Frozena, RN
Teresa G. Odle

I Catatonia
Definition
Catatonia is a condition marked by changes in
muscle tone or activity associated with a large number
of serious mental and physical illnesses. There are two
distinct sets of symptoms that are characteristic of
this condition. In catatonic stupor the individual
GALE ENCYCLOPEDIA OF MEDICINE

Other signs and symptoms include violence directed
toward him/herself, the assumption of inappropriate
posture, selective mutism, negativism, facial grimaces, and animal-like noises.

Features of catatonia may also be seen in
Neuroleptic Malignant Syndrome (NMS) which is an
uncommon (but potentially lethal) reaction to some
medications used to treat major mental illnesses. NMS
is considered a medical emergency since 25% of
untreated cases result in death. Catatonia can also be
present in individuals suffering from a number of
other physical and emotional conditions such as drug
intoxication, depression, and schizophrenia. It is most
commonly associated with mood disorders.

Catatonic stupor is marked by immobility and a
behavior known as cerea flexibilitas (waxy flexibility)
in which the individual can be made to assume bizarre
(and sometimes painful) postures that they will maintain for extended periods of time. The individual may
become dehydrated and malnourished because food
and liquids are refused. In extreme situations such
individuals must be fed through a tube. Catatonic
excitement is characterized by hyperactivity and violence; the individual may harm him/herself or others.
On rare occasions, isolation or restraint may be
needed to ensure the individual’s safety and the safety
of others.

Description
In catatonic stupor, motor activity may be reduced
to zero. Individuals avoid bathing and grooming,
make little or no eye contact with others, may be
mute and rigid, and initiate no social behaviors. In
catatonic excitement the individual is extremely hyperactive although the activity seems to have no purpose.
Violence toward him/herself or others may also be
seen.
NMS is observed as a dangerous side effect associated with certain neuroleptic (antipsychotic) drugs
such as haloperidol (Haldol). It comes on suddenly
and is characterized by stiffening of the muscles,
fever, confusion and heavy sweating.
Catatonia can also be categorized as intrinsic or
extrinsic. If the condition has an identifiable cause, it is
designated as extrinsic. If no cause can be determined
following physical examination, laboratory testing,
and history taking, the illness is considered to be
intrinsic.

Causes and symptoms
The causes of catatonia are largely unknown
although research indicates that brain structure and
function are altered in this condition. While this and
other information point to a physical cause, none has
yet been proven. A variety of medical conditions also
may lead to catatonia including head trauma, cerebrovascular disease, encephalitis, and certain metabolic
disorders. NMS is an adverse side effect of certain
antipsychotic drugs.
A variety of symptoms are associated with
catatonia. Among the more common are echopraxia
(imitation of the gestures of others) and echolalia
(parrot-like repetition of words spoken by others).
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Recognition of catatonia is made on the basis of
specific movement symptoms. These include odd ways
of walking such as walking on tiptoes or ritualistic
pacing, and rarely, hopping and skipping. Repetitive
odd movements of the fingers or hands, as well as
imitating the speech or movements of others also
may indicate that catatonia is present. There are no
laboratory or other tests that can be used to positively
diagnose this condition, but medical and neurological
tests are necessary to rule out underlying lesions or
disorders that may be causing the symptoms observed.

Treatment
Treatment of catatonia includes medications such
as benzodiazipines (which are the preferred treatment)
and rarely barbiturates. Antipsychotic drugs may be
appropriate in some cases, but often cause catatonia to
worsen. Electroconvulsive therapy may prove beneficial for clients who do not respond to medication. If
these approaches are unsuccessful, treatment will be
redirected to attempts to control the signs and symptoms of the illness.

Prognosis
Catatonia usually responds quickly to medication
interventions.

Prevention
There is currently no known way to prevent catatonia because the cause has not yet been identified.
Research efforts continue to explore possible origins.
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Catatonia

experiences a deficit of motor (movement) activity that
can render him/her motionless. Catatonic excitement,
or excessive movement, is associated with violent
behavior directed toward oneself or others.

Catecholamines tests

KEY TERMS
Barbiturates—A group of medicines that slow
breathing and lower the body temperature and
blood pressure. They can be habit forming and are
now used chiefly for anesthesia.
Benzodiazipines—This group of medicines is used
to help reduce anxiety (especially before surgery)
and to help people sleep.
Electroconvulsive therapy—This type of therapy
is used to treat major depression and severe
mental illness that does not respond to medications. A measured dose of electricity is introduced
into the brain in order to produce a convulsion.
Electroconvulsive therapy is safe and effective.
Mutism—The inability or refusal to speak.
Negativism—Behavior characterized by resistance, opposition, and refusal to cooperate with
requests, even the most reasonable ones.
Neuroleptic drugs—Antipsychotic drugs, including major tranquilizers, used in the treatment of
psychoses like schizophrenia.

Avoiding excessive use of neuroleptic drugs can
help minimize the risk of developing catatonic-like
symptoms.
Resources
BOOKS

Frisch, Noreen Cavan, and Lawrence E. Frisch. Psychiatric
Mental Health Nursing. Albany, NY: Delmar
Publishers, 1998.

Donald G. Barstow, RN

I Catecholamines tests
Definition
Catecholamines is a collective term for the hormones epinephrine, norepinephrine, and dopamine.
Manufactured chiefly by the chromaffin cells of the
adrenal glands, these hormones are involved in readying the body for the ‘‘fight-or-flight’’ response (also
known as the alarm reaction). When these hormones
are released, the heart beats stronger and faster, blood
pressure rises, more blood flows to the brain and
754

muscles, the liver releases stores of energy as a sugar
the body can readily use (glucose), the rate of breathing increases and airways widen, and digestive activity
slows. These reactions direct more oxygen and fuel to
the organs most active in responding to stress–mainly
the brain, heart, and skeletal muscles.

Purpose
Pheochromocytoma (a tumor of the chromaffin
cells of the adrenal gland) and tumors of the nervous
system (neuroblastomas, ganglioneuroblastomas, and
ganglioneuromas) that affect hormone production can
cause excessive levels of different catecholamines to be
secreted. This results in constant or intermittent
high blood pressure (hypertension). Episodes of high
blood pressure may be accompanied by symptoms
such as headache, sweating, palpitations, and anxiety.
The catecholamines test can be ordered, then, to determine if high blood pressure and other symptoms are
related to improper hormone secretion and to identify
the type of tumor causing elevated catecholamine levels.

Description
The catecholamines test can be performed on
either blood or urine. If performed on blood, the test
may require one or two samples, depending on the
physician’s request. The first blood sample will be
drawn after the patient has been lying down in a
warm, comfortable environment for at least 30 minutes. If a second sample is needed, the patient will be
asked to stand for 10 minutes before the blood is
drawn. Instead of a venipuncture, which can be stressful for the patient, possibly increasing catecholamine
levels in the blood, a plastic or rubber tube-like device
called a catheter may be used to collect the blood
samples. The catheter would be inserted in a vein
24 hours in advance, eliminating the need for needle
punctures at the time of the test.
It may take up to a week for a lab to complete
testing of the samples. Because blood levels of catecholamines commonly go up and down in response to such
factors as temperature, stress, postural change, diet,
smoking, obesity, and many drugs, abnormally high
blood test results should be confirmed with a 24-hour
urine test. In addition, catecholamine secretion from a
tumor may not be steady, but may occur periodically
during the day, and potentially could be missed when
blood testing is used. The urine test provides the laboratory with a specimen that reflects catecholamine production over an entire 24-hour period. If urine is tested,
the patient or a healthcare worker must collect all the
urine passed over the 24-hour period.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

It is important that the patient refrain from using
certain medications, especially cold or allergy remedies,
for two weeks before the test. Certain foods–including
bananas, avocados, cheese, coffee, tea, cocoa, beer,
licorice, citrus fruit, vanilla, and Chianti–must be
avoided for 48 hours prior to testing. However, people
should be sure to get adequate amounts of vitamin C
before the test, because this vitamin is necessary for
catecholamine formation. The patient should be fasting
(nothing to eat or drink) for 10 to 24 hours before
the blood test and should not smoke for 24 hours
beforehand. Some laboratories may call for additional
restrictions. As much as possible, the patient should try
to avoid excessive physical exercise and emotional
stress before the test, because either may alter test
results by causing increased secretion of epinephrine
and norepinephrine.

Dopamine—Dopamine is a precursor of epinephrine
and norepinephrine.
Epinephrine— Epinephrine, also called adrenaline,
is a naturally occurring hormone released by
the adrenal glands in response to signals from the
sympathetic nervous system. These signals are triggered by stress, exercise, or by emotions such as
fear.
Ganglioneuroma—A ganglioneuroma is a tumor
composed of mature nerve cells.
Neuroblastoma—Neuroblastoma is a tumor of the
adrenal glands or sympathetic nervous system.
Neuroblastomas can range from being relatively
harmless to highly malignant.
Norepinephrine—Norepinephrine is a hormone
secreted by certain nerve endings of the sympathetic nervous system, and by the medulla (center)
of the adrenal glands. Its primary function is to help
maintain a constant blood pressure by stimulating
certain blood vessels to constrict when the blood
pressure falls below normal.

Patients collecting their own 24-hour urine samples will be given a container with special instructions.
The urine samples must be refrigerated.

Risks
Risks for the blood test are minimal, but may
include slight bleeding from the venipuncture site,
fainting or feeling lightheaded after blood is drawn,
or blood accumulating under the puncture site (hematoma). There are no risks for the urine test.

Pheochromocytoma—A pheochromocytoma is a
tumor that originates from the adrenal gland’s chromaffin cells, causing overproduction of catecholamines, powerful hormones that induce high blood
pressure and other symptoms.

Normal results
Reference ranges are laboratory-specific, vary
according to methodology of testing, and differ
between blood and urine samples. If testing is done
by the method called High Performance Liquid
Chromatography (HPLC), typical values for blood
and urine follow.

Abnormal results
Depending on the results, high catecholamine
levels can indicate different conditions and/or causes:


High catecholamine levels can help to verify pheochromocytoma, neuroblastoma, or ganglioneuroma.
An aid to diagnosis is the fact that an adrenal medullary tumor (pheochromocytoma) secretes epinephrine, whereas ganglioneuroma and neuroblastoma
secrete norepinephrine.



Elevations are possible with, but do not directly
confirm, thyroid disorders, low blood sugar (hypoglycemia), or heart disease.



Electroshock therapy, or shock resulting from
hemorrhage or exposure to toxins, can raise catecholamine levels.



In the patient with normal or low baseline catecholamine levels, failure to show an increase in the sample
taken after standing suggests an autonomic nervous

Reference ranges for blood catecholamines
Supine (lying down): Epinephrine less than
50 pg/mL, norepinephrine less than 410 pg/mL, and
dopamine less than 90 pg/mL. Standing: Values for
blood specimens taken when the subject is standing are higher than the ranges for supine posture
for norepinephrine and epinephrine, but not for
dopamine.
Reference ranges for urine catecholamines
Epinephrine 0–20 micrograms per 24 hours; norepinephrine 15–80 micrograms per 24 hours; dopamine
65–400 micrograms per 24 hours.
GALE ENCYCLOPEDIA OF MEDICINE

755

Catecholamines tests

Preparation

Catheter ablation

system dysfunction (the division of the nervous system
responsible for the automatic or unconscious regulation of internal body functioning).

arrhythmia must be clearly defined before this procedure can be properly done.

Description

Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

I Catheter ablation
Definition
Catheter ablation of an irregular heartbeat
involves having a tube (a catheter) inserted into the
heart through which electrical energy is sent to either
reset the heartbeat or stop the heart from beating so a
mechanical pacemaker can be put in place.

Purpose
Irregular heartbeats can occur in healthy people
without causing any dangerous symptoms or requiring
medical attention. Slight changes in the normal patterns of heartbeats often reset themselves without
notice.
But when the heartbeat is greatly disrupted–either
because of traumatic injury, disease, hypertension, surgery, or reduced blood flow to the heart caused by
blockages in the blood vessels that nourish the heart–
the condition must be recognized and treated immediately. Otherwise, it can be fatal.
Various drugs can be used to control and help reset
these abnormal heart rhythms (arrhythmias). The technique of catheter ablation (meaning tube-guided
removal) is used to interrupt the abnormal contractions
in the heart, allowing normal heart beating to resume.
Atrial fibrillation and flutter and Wolff-ParkinsonWhite syndrome are two of the most common disorders
treated with catheter ablation.

Catheter ablation involves delivering highly
focused heat (or radio frequency energy) to specific
areas of the heart. Radio frequency energy is very
rapidly alternating electrical current that is produced
at the tip of the catheter that is placed inside the heart.
At the same time as the catheter is inserted, a second
electrode is placed on the patient’s skin. When the
catheter is energized, the body conducts the energy
from the catheter’s tip, through the heart and to the
electrode on the skin’s surface, completing the circuit.
Although very little electricity is given off by the
catheter, the instrument does generate a large amount of
heat. This heat is absorbed by the heart tissue, causing a
small localized burn and destroying the tissue in contact
with the catheter tip; in this way, small regions of heart
tissue are burned in a controlled manner. This controlled destruction of small sections of heart muscle
actually kills the nerve cells causing the irregular heartbeat, stopping the nerve signals that are passing through
this section of the heart. This usually causes the irregular
heartbeat to be reset into a normal heartbeat.

Preparation
People can undergo this procedure by having
general anesthesia or by taking medicines to make
them relaxed and sleepy (sedatives) along with painkillers. Once the type of irregular heartbeat is identified and these medicines are given, the catheter is
inserted through a blood vessel and into the heart.
Importantly, correct placement of the catheter is
visualized by using a specialized type of x-ray machine
called a fluoroscope.

Aftercare
Being sure the patient is comfortable during and
after this procedure is very important. However,
because each person may have a different arrhythmia
and possibly other medical problems as well, each
patient’s needs must be evaluated individually.

Risks
Precautions
The improper correction of abnormal heartbeats
can cause additional arrhythmias and can be fatal.
Abnormalities in different areas of the heart cause
different types of irregular heartbeats; the type of
756

Overall, fewer than 5% of people having this
procedure experience complications. The most common complications are usually related to blood vessel
injury when the catheter is inserted and to different
heart-related problems due to the moving of the
GALE ENCYCLOPEDIA OF MEDICINE

Catheter ablation
During catheter ablation, a long flexible tube called a catheter is inserted into a vein in the patient’s groin and guided toward the
heart. A special x-ray machine called a fluoroscope helps the electrophysiologist visualize correct placement. (Photograph by
Collette Placek. Reproduced by permission.)

KEY TERMS
Fluoroscope—A specialized x-ray machine used
to visualize the placement of the catheter when
attempting to correct irregular heartbeats.
Pacemaker—An electrical device that has electrodes attached to the heart to electrically stimulate
the heart to beat normally. Pacemakers can be
internal (placed under the skin) or external, with
the electrodes placed on the skin or threaded
through a tube placed into the heart.

catheter within the heart. However, in general, this
technique is safe and can control many different heart
arrhythmias.
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Depending upon the type of irregular heartbeat
being treated, either the normal heartbeat resumes
after treatment or the ability of the heart to beat on
its own is lost, requiring the insertion of a pacemaker
to stimulate the heart to beat regularly.

Abnormal results
Additional irregular heartbeats can occur as a
result of this procedure, as can damage to the blood
vessels that feed the heart. Because this procedure
requires the use of the x-ray machine called a fluoroscope, there is exposure to x-ray radiation, but it is
doubtful that this is harmful in adult patients. The
risk versus benefit is considered with pediatric patients.
757

Celiac disease

Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave.
Dallas, TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dominic De Bellis, PhD

Cat’s cry syndrome see Cri du chat syndrome
CBC see Blood count
CEA test see Carcinoembryonic antigen test
CEB see Chronic fatigue syndrome
Cefaclor see Cephalosporins
Cefadroxil see Cephalosporins
Cefixime see Cephalosporins
Cefprozil see Cephalosporins
Cefurox see Cephalosporins

I Celiac disease
Definition
Celiac disease is a disease of the digestive system
that damages the small intestine and interferes with
the absorption of nutrients from food.

Description
Celiac disease occurs when the body reacts abnormally to gluten, a protein found in wheat, rye, barley,
and possibly oats. When someone with celiac disease
eats foods containing gluten, that person’s immune
system causes an inflammatory response in the small
intestine, which damages the tissues and results in
impaired ability to absorb nutrients from foods. The
inflammation and malabsorption create wide-ranging
problems in many systems of the body. Since the
body’s own immune system causes the damage, celiac
disease is classified as an ‘‘autoimmune’’ disorder.
Celiac disease may also be called sprue, nontropical
sprue, gluten sensitive enteropathy, celiac sprue, and
adult celiac disease.
Celiac disease may be discovered at any age,
from infancy through adulthood. The disorder is
more commonly found among white Europeans or in
people of European descent. It is very unusual to find
celiac disease in African or Asian people. The exact
758

incidence of the disease is uncertain. Estimates vary
from one in 5000, to as many as one in every 300
individuals with this background. The prevalence of
celiac disease seems to be different from one European
country to another, and between Europe and the
United States. This may be due to differences in diet
and/or unrecognized disease. A recent study of random blood samples tested for celiac disease in the US
showed one in 250 testing positive. It is clearly underdiagnosed, probably due to the symptoms being
attributed to another problem, or lack of knowledge
about celiac disease by physicians and laboratories.
Because of the known genetic component, relatives
of patients with celiac disease are considered at higher
risk for the disorder.
Because celiac disease has a hereditary influence,
close relatives (especially first degree relatives, such as
children, siblings, and parents) have a higher risk of
being affected with the condition. The chance that a
first degree relative of someone with celiac disease will
have the disease is about 10%.
As more is learned about celiac disease, it becomes
evident that it has many variations which may not
produce typical symptoms. It may even be clinically
‘‘silent,’’ where no obvious problems related to the
disease are apparent.

Causes and symptoms
Celiac disease can run in families and has a genetic
basis, although the pattern of inheritance is complicated. The type of inheritance pattern that celiac disease
follows is called multifactorial (caused by many factors,
both genetic and environmental). Researchers think
that several factors must exist in order for the disease
to occur. The patient must have a genetic predisposition
to develop the disorder. Then, something in their environment acts as a stimulus, or ‘‘trigger,’’ to their immune
system, causing the disease to become active for the first
time. For conditions with multifactorial inheritance,
people without the genetic predisposition are less likely
to develop the condition with exposure to the same
triggers. Or, they may require more exposure to the
stimulus before developing the disease than someone
with a genetic predisposition. Some of the things which
may provoke a reaction include surgery, especially gastrointestinal surgery; a change to a low fat diet, which
has an increased number of wheat-based foods; pregnancy; childbirth; severe emotional stress; or a viral
infection. This combination of genetic susceptibility
and an outside agent leads to celiac disease.
Each person with celiac disease is affected differently. When food containing gluten reaches the small
GALE ENCYCLOPEDIA OF MEDICINE

The most commonly recognized symptoms of
celiac disease relate to the improper absorption of
food in the gastrointestinal system. Many patients
with gastrointestinal symptoms will have diarrhea
and fatty, greasy, unusually foul-smelling stools. The
patient may complain of excessive gas (flatulence),
distended abdomen, weight loss, and generalized
weakness. Not all people have digestive system complications; some people only have irritability or
depression. Irritability is one of the most common
symptoms in children with celiac disease.
Not all patients have these problems. Unrecognized
and therefore untreated celiac disease may cause or contribute to a variety of other conditions. The decreased
ability to digest, absorb, and utilize food properly
(malabsorption) may cause anemia (low red blood
count) from iron deficiency or easy bruising from a lack
of vitamin K. Poor mineral absorption may result in
osteoporosis, or ‘‘brittle bones,’’ which may lead to
bone fractures. Vitamin D levels may be insufficient
and bring about a ‘‘softening’’ of bones (osteomalacia),
which produces pain and bony deformities, such as flattening or bending. Defects in the tooth enamel, characteristic of celiac disease, may be recognized by dentists.
Celiac disease may be discovered during medical tests
performed to investigate failure to thrive in infants, or
lack of proper growth in children and adolescents.
People with celiac disease may also experience lactose
intolerance because they don’t produce enough of
the enzyme lactase, which breaks down the sugar in
milk into a form the body can absorb. Other symptoms
can include muscle cramps, fatigue, delayed growth, tingling or numbness in the legs (from nerve damage), pale
sores in the mouth (called aphthus ulcers), tooth discoloration, or missed menstrual periods (due to severe
weight loss).
A distinctive, painful skin rash, called dermatitis
herpetiformis, may be the first sign of celiac disease.
Approximately 10% of patients with celiac disease
have this rash, but it is estimated that 85% or more
of patients with the rash have the disease.
Many disorders are associated with celiac disease, though the nature of the connection is unclear.
GALE ENCYCLOPEDIA OF MEDICINE

One type of epilepsy is linked to celiac disease.
Once their celiac disease is successfully treated, a
significant number of these patients have fewer or
no seizures. Patients with alopecia areata, a condition
where hair loss occurs in sharply defined areas, have
been shown to have a higher risk of celiac disease
than the general population. There appears to be a
higher percentage of celiac disease among people
with Down syndrome, but the link between the conditions is unknown.
Several conditions attributed to a disorder of the
immune system have been associated with celiac disease. People with insulin dependent diabetes (type I)
have a much higher incidence of celiac disease. One
source estimates that as many as one in 20 insulindependent diabetics may have celiac disease. Patients
with other conditions where celiac disease may be
more commonly found include those with juvenile
chronic arthritis, some thyroid diseases, and IgA
deficiency.
There is an increased risk of intestinal lymphoma,
a type of cancer, in individuals with celiac disease.
Successful treatment of the celiac disease seems to
decrease the chance of developing lymphoma.

Diagnosis
Because of the variety of ways celiac disease can
manifest itself, it is often not discovered promptly. Its
symptoms are similar to many other conditions
including irritible bowel syndrome, Crohn’s disease,
ulcerative colitis, diverticulosis, intestinal infections,
chronic fatigue syndrome, and depression. The condition may persist without diagnosis for so long that the
patient accepts a general feeling of illness as normal.
This leads to further delay in identifying and treating
the disorder. It is not unusual for the disease to be
identified in the course of medical investigations for
seemingly unrelated problems. For example, celiac
disease has been discovered during testing to find the
cause of infertility.
If celiac disease is suspected, a blood test can be
ordered. This test looks for the antibodies to gluten
(called antigliadin, anti-endomysium, and antireticulin) that the immune system produces in celiac disease.
Antibodies are chemicals produced by the immune
system in response to substances that the body perceives to be threatening. Some experts advocate not
just evaluating patients with symptoms, but using
these blood studies as a screening test for high-risk
individuals, such as those with relatives (especially
first degree relatives) known to have the disorder. An
abnormal result points towards celiac disease, but
759

Celiac disease

intestine, the immune system begins to attack a substance called gliadin, which is found in the gluten. The
resulting inflammation causes damage to the delicate
finger-like structures in the intestine, called villi, where
food absorption actually takes place. The patient may
experience a number of symptoms related to the inflammation and the chemicals it releases, and/or the lack of
ability to absorb nutrients from food, which can cause
malnutrition.

Celiac disease

further tests are needed to confirm the diagnosis.
Because celiac disease affects the ability of the body
to absorb nutrients from food, several tests may be
ordered to look for nutritional deficiencies. For example, doctors may order a test of iron levels in the blood
because low levels of iron (anemia) may accompany
celiac disease. Doctors may also order a test for fat in
the stool, since celiac disease prevents the body from
absorbing fat from food.
If these tests above are suspicious for celiac disease, the next step is a biopsy (removal of a tiny piece
of tissue surgically) of the small intestine. This is
usually done by a gastroenterologist, a physician
who specializes in diagnosing and treating bowel disorders. It is generally performed in the office, or in a
hospital’s outpatient department. The patient
remains awake, but is sedated. A narrow tube, called
an endoscope, is passed through the mouth, down
through the stomach, and into the small intestine.
A small sample of tissue is taken and sent to the
laboratory for analysis. If it shows a pattern of tissue
damage characteristic of celiac disease, the diagnosis
is established.
The patient is then placed on a gluten-free diet
(GFD). The physician will periodically recheck the
level of antibody in the patient’s blood. After several
months, the small intestine is biopsied again. If the
diagnosis of celiac disease was correct (and the patient
followed the rigorous diet), healing of the intestine will
be apparent. Most experts agree that it is necessary to
follow these steps in order to be sure of an accurate
diagnosis.

Treatment
The only treatment for celiac disease is a glutenfree diet. This may be easy for the doctor to prescribe,
but difficult for the patient to follow. For most people,
adhering to this diet will stop symptoms and prevent
damage to the intestines. Damaged villi can be functional again in three to six months. This diet must be
followed for life. For people whose symptoms are
cured by the gluten-free diet, this is further evidence
that their diagnosis is correct.
Gluten is present in any product that contains
wheat, rye, barley, or oats. It helps make bread rise,
and gives many foods a smooth, pleasing texture.
In addition to the many obvious places gluten can
be found in a normal diet, such as breads, cereals,
and pasta, there are many hidden sources of gluten.
These include ingredients added to foods to improve
texture or enhance flavor and products used in food
760

KEY TERMS
Antibodies—Proteins that provoke the immune
system to attack particular substances. In celiac
disease, the immune system makes antibodies to a
component of gluten.
Gluten—A protein found in wheat, rye, barley, and
oats.
Villi—Tiny, finger-like projections that enable the
small intestine to absorb nutrients from food.

packaging. Gluten may even be present on surfaces
used for food preparation or cooking.
Fresh foods that have not been artificially processed,
such as fruits, vegetables, and meats, are permitted as
part of a GFD. Gluten-free foods can be found in
health food stores and in some supermarkets. Mailorder food companies often have a selection of glutenfree products. Help in dietary planning is available from
dieticians (healthcare professionals specializing in food
and nutrition) or from support groups for individuals
with celiac disease. There are many cookbooks on the
market specifically for those on a GFD.
Treating celiac disease with a GFD is almost
always completely effective. Gastrointestinal complaints
and other symptoms are alleviated. Secondary complications, such as anemia and osteoporosis, resolve in almost
all patients. People who have experienced lactose intolerance related to their celiac disease usually see those
symptoms subside, as well. Although there is no risk
and much potential benefit to this treatment, it is clear
that avoiding all foods containing gluten can be difficult.
Experts emphasize the need for lifelong adherence
to the GFD to avoid the long-term complications of
this disorder. They point out that although the disease
may have symptom-free periods if the diet is not followed, silent damage continues to occur. Celiac disease cannot be ‘‘outgrown’’ or cured, according to
medical authorities.

Prognosis
Patients with celiac disease must adhere to a strict
GFD throughout their lifetime. Once the diet has been
followed for several years, individuals with celiac disease have similar mortality rates as the general population. However, about 10% of people with celiac
disease develop a cancer involving the gastrointestinal
tract (both carcinoma and lymphoma).
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
There is no way to prevent celiac disease.
However, the key to decreasing its impact on overall
health is early diagnosis and strict adherence to the
prescribed gluten-free diet.

Purpose
Cell therapy has been used successfully to rebuild
damaged cartilage in joints, repair spinal cord
injuries, strengthen a weakened immune system, treat
autoimmune diseases such as AIDS, and help patients
with neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and epilepsy. Further uses
have shown positive results in the treatment of a wide
range of chronic conditions such as arteriosclerosis,
congenital defects, and sexual dysfunction. The therapy has also been used to treat cancer patients at a
number of clinics in Tijuana, Mexico, although this
application has not been well supported with controlled clinical studies.

Description
Resources

Origins

PERIODICALS

Gluten-Free Living, (Bimonthly newsletter). PO Box 105,
Hastings-on-Hudson, NY 10706.
ORGANIZATIONS

American Celiac Society. 58 Musano Court, West Orange,
NJ 07052. (201) 325-8837.
Celiac Disease Foundation. 13251 Ventura Blvd., Suite 1,
Studio City, CA 91604-1838. (818) 990-2354. <http://
www.cdf@celiac.org>.
Celiac Sprue Association/United States of America (CSA/
USA). PO Box 31700, Omaha, NE 68131-0700. (402)
558-0600.
Gluten Intolerance Group. PO Box 23053, Seattle, WA
98102-0353. (206) 325-6980.
National Center for Nutrition and Dietetics. American
Dietetic Association, 216 West Jackson Boulevard,
Suite 800, Chicago, IL 60606-6995. (800) 366-1655.
OTHER

National Institute of Diabetes & Digestive & Kidney
Diseases. <http://www.niddk.nih.gov/health/digest/
pubs/celiac/index.htm>.

Amy Vance, MS, CGC

I Cell therapy
Definition
Cell therapy is the transplantation of human
or animal cells to replace or repair damaged tissue
and/or cells.
GALE ENCYCLOPEDIA OF MEDICINE

The theory behind cell therapy has been in existence for several hundred years. The first recorded
discussion of the concept of cell therapy can be traced
to Phillippus Aureolus Paracelsus (1493–1541), a
German-Swiss physician and alchemist who wrote in
his Der grossen Wundartzney (‘‘Great Surgery Book’’)
in 1536 that ‘‘the heart heals the heart, lung heals the
lung, spleen heals the spleen; like cures like.’’
Paracelsus and many of his contemporaries agreed
that the best way to treat an illness was to use living
tissue to restore the ailing. In 1667, at a laboratory in
the palace of Louis XIV, Jean-Baptiste Denis (1640–
1704) attempted to transfuse blood from a calf into a
mentally ill patient—and since blood transfusion is, in
effect, a form of cell therapy, this could be the first
documented case of this procedure. However, the first
recorded attempt at non-blood cellular therapy
occurred in 1912 when German physicians attempted
to treat children with hypothyroidism, or an underactive thyroid, with thyroid cells.
In 1931, Dr. Paul Niehans (1882–1971), a Swiss
physician, became known as ‘‘the father of cell therapy’’ quite by chance. After a surgical accident by a
colleague, Niehans attempted to transplant a patient’s
severely damaged parathyroid glands with those of a
steer. When the patient began to rapidly deteriorate
before the transplant could take place, Niehans
decided to dice the steer’s parathyroid gland into fine
pieces, mix the pieces in a saline solution, and inject
them into the dying patient. Immediately, the patient
began to improve and, in fact, lived for another 30
years.
Cell therapy is, in effect, a type of organ transplant which has also been referred to as ‘‘live cell
761

Cell therapy

There are a small number of patients who
develop a refractory type of celiac disease, where
the GFD no longer seems effective. Once the diet
has been thoroughly assessed to ensure no hidden
sources of gluten are causing the problem, medications may be prescribed. Steroids or immunosuppressant drugs are often used to try to control the disease.
It is unclear whether these efforts meet with much
success.

Cell therapy

P A U L N I E H A N S (1882–1971)
Niehans enlisted in the Swiss Army in 1912. When
war erupted in the Balkans, Niehans set up a hospital in
Belgrade, Yugoslavia. The war provided him the opportunity to treat numerous patients, gaining a firsthand knowledge of the body and its workings.
Since 1913, Niehans had been intrigued with Alexis
Carrel’s experiments concerning the adaptive abilities of
cells, though Niehans himself specialized in glandular
transplants and by 1925 was one of the leading glandular
surgeons in Europe.
Niehans referred to 1931 as the birth year of cellular
therapy. That year, he treated a patient suffering from
tetany whose parathyroid had been erroneously removed
by another physician. Too weak for a glandular transplant,
the patient was given injections of the parathyroid glands
of steer, and she soon recovered. Niehans made more
injections, even experimenting on himself, and reported
he could cure illnesses through injections of live cells
extracted from healthy animal organs. He believed adding
new tissue stimulated rejuvenation and recovery.
(AP/Wide World Photos. Reproduced by permission.)

Paul Niehans was born and raised in Switzerland. His
father, a doctor, was dismayed when he entered the seminary, but Niehans quickly grew dissatisfied with religious
life and took up medicine after all. He first studied at Bern,
then completed an internship in Zurich.

therapy,’’ ‘‘xenotransplant therapy,’’ ‘‘cellular suspensions,’’ ‘‘glandular therapy,’’ or ‘‘fresh cell therapy.’’
The procedure involves the injection of either whole
fetal xenogenic (animal) cells (e.g., from sheep, cows,
pigs, and sharks) or cell extracts from human tissue.
The latter is known as autologous cell therapy if the
cells are extracted from and transplanted back into
the same patient. Several different types of cells can
be administered simultaneously.
Just as Paracelsus’s theory of ‘‘like cures like,’’ the
types of cells that are administered correspond in some
way with the organ or tissue in the patient that is failing.
No one knows exactly how cell therapy works, but
proponents claim that the injected cells travel to the
similar organ from which they were taken to revitalize
and stimulate that organ’s function and regenerate its
cellular structure. In other words, the cells are not
species specific, but only organ specific. Supporters of
cellular treatment believe that embryonic and fetal animal tissue contain active therapeutic agents distinct
from vitamins, minerals, hormones, or enzymes.
762

Niehans treated Pope Pious XII with his injections and
was nominated to the Vatican Academy of Science following the pope’s recovery.
Niehans remained a controversial figure throughout
his life. As of 2000, the Clinique Paul Niehans in
Switzerland, founded by his daughter, continued his work.

Swedish researchers have successfully transplanted human fetal stem cells into human recipients,
and the procedure is being investigated further as a
possible treatment for repairing brain cells in
Parkinson’s patients. However, because the cells used
in these applications must be harvested from aborted
human fetuses, there is an ethical debate over their use.
Currently, applications of cell therapy in the
United States is still in the research, experimental,
and clinical trial stages. The U.S. Food and Drug
Administration has approved the use of one cellular
therapy technique for repairing damaged knee joints.
The procedure involves removing healthy chondrocyte cells, the type of cell that forms cartilage, from
the patient, culturing them in a laboratory for three to
four weeks, and then transplanting them back into the
damaged knee joint of the patient.

Preparations
There are several processes to prepare cells for
use. One form involves extracting cells from the
GALE ENCYCLOPEDIA OF MEDICINE

Anaphylactic shock—A severe allergic reaction
that causes blood pressure drop, racing heart, swelling of the airway, rash, and possibly convulsions.
Culturing—To grow cells in a special substance, or
media, in the laboratory.
Encephalitis—Inflammation of the brain.

patient they are to be used on and then culturing them
in a laboratory setting until they multiply to the level
needed for transplant back into the patient. Another
procedure uses freshly removed fetal animal tissue,
which has been processed and suspended in a saline
solution. The preparation of fresh cells then may be
either injected immediately into the patient, or preserved by being freeze-dried or deep-frozen in liquid
nitrogen before being injected. Cells may be tested
for pathogens, such as bacteria, viruses, or parasites,
before use.

Precautions
Patients undergoing cell therapy treatments which
use cells transplanted from animals or other humans
run the risk of cell rejection, in which the body recognizes the cells as a foreign substance and uses the
immune system’s T-cells to attack and destroy them.
Some forms of cell therapy use special coatings on the
cells designed to trick the immune system into recognizing the new cells as native to the body.
There is also the chance of the cell solution transmitting bacterial or viral infection or other disease and
parasites to the patient. Careful screening and testing
of cells for pathogens can reduce this risk.
Many forms of cell therapy in the United States
are still largely experimental procedures. Patients
should approach these treatments with extreme caution, should inquire about their proven efficacy and
legal use in the United States, and should only accept
treatment from a licensed physician who should educate the patient completely on the risks and possible
side effects involved with cell therapy. These same
cautions apply for patients interested in participating
in clinical trials of cell therapy treatments.

Side effects
Because cell therapy encompasses such a wide
range of treatments and applications, and many of
GALE ENCYCLOPEDIA OF MEDICINE

these treatments are still experimental, the full range
of possible side effects of the treatments are not yet
known. Anaphylactic shock (severe allergic reaction),
immune system reactions, and encephalitis (inflammation of the brain) are just a few of the known reported
side effects in some patients.
Side effects of the FDA–approved chondrocyte
cell therapy used in knee joint repair may include
tissue hypertrophy, a condition where too much cartilage grows in the joint where the cells were transplanted to and the knee joint begins to stiffen.

Research and general acceptance
There is a growing debate in the medical community over the efficacy and ethical implications of cell
therapy. Much of the ethical debate revolves around the
use of human fetal stem cells in treatment, and the fact
that these cells must be harvested from aborted fetuses.
While some cell therapy procedures have had
proven success in clinical studies, others are still largely unproven, including cell therapy for cancer
treatment. Until more large, controlled clinical studies are performed on these procedures to either
prove or disprove their efficacy, they will remain
fringe treatments.
Resources
PERIODICALS

Sinha, Gunjan. ‘‘On the Road to Recovery: Fetal pig cell
therapy has put Parkinson’s patient Jim Finn back
in the driver’s seat.’’ Popular Science 255, no. 4 (Oct
1999): 27.
ORGANIZATIONS

Center for Cell and Gene Therapy. Baylor College of
Medicine. 1102 Bates St, Suite 1100, Houston,
Texas 77030-2399. (713) 770-4663. <http://
www.bcm.tmc.edu/genetherapy>.

Paula Anne Ford-Martin

I Cellulitis
Definition
Cellulitis is a spreading bacterial infection
just below the skin surface. It is most commonly
caused by Streptococcus pyogenes or Staphylococcus
aureus.
763

Cellulitis

KEY TERMS

Cellulitis

Description
The word ‘‘cellulitis’’ actually means ‘‘inflammation of the cells.’’ Specifically, cellulitis refers to an
infection of the tissue just below the skin surface. In
humans, the skin and the tissues under the skin are the
most common locations for microbial infection. Skin
is the first defense against invading bacteria and other
microbes. An infection can occur when this normally
strong barrier is damaged due to surgery, injury, or a
burn. Even something as small as a scratch or an insect
bite allows bacteria to enter the skin, which may lead
to an infection. Usually, the immune system kills any
invading bacteria, but sometimes the bacteria are able
to grow and cause an infection.
Once past the skin surface, the warmth, moisture,
and nutrients allow bacteria to grow rapidly. Diseasecausing bacteria release proteins called enzymes which
cause tissue damage. The body’s reaction to damage is
inflammation which is characterized by pain, redness,
heat, and swelling. This red, painful region grows bigger
as the infection and resulting tissue damage spread. An
untreated infection may spread to the lymphatic system
(acute lymphangitis), the lymph nodes (lymphadenitis),
the bloodstream (bacteremia), or into deeper tissues.
Cellulitis most often occurs on the face, neck, and legs.
Orbital cellulitis
A very serious infection, called orbital cellulitis,
occurs when bacteria enter and infect the tissues surrounding the eye. In 50–70% of all cases of orbital
cellulitis, the infection spreads to the eye(s) from the
sinuses or the upper respiratory tract (nose and
throat). Twenty-five percent of orbital infections
occur after surgery on the face. Other sources of orbital infection include a direct infection from an eye
injury, from a dental or throat infection, and through
the bloodstream.
Infection of the tissues surrounding the eye causes
redness, swollen eyelids, severe pain, and causes the
eye to bulge out. This serious infection can lead to a
temporary loss of vision, blindness, brain abscesses,
inflammation of the brain and spinal tissues (meningitis), and other complications. Before the discovery of
antibiotics, orbital cellulitis caused blindness in 20% of
patients and death in 17% of patients. Antibiotic treatment has significantly reduced the incidence of blindness and death.

Causes and symptoms
Although other kinds of bacteria can cause cellulitis, it is most often caused by Streptococcus pyogenes
764

(the bacteria which causes strep throat) and
Staphylococcus aureus. Streptococcus pyogenes is the
so-called ‘‘flesh-eating bacteria’’ and, in rare cases, can
cause a dangerous, deep skin infection called necrotizing fasciitis. Orbital cellulitis may be caused by bacteria which cannot grow in the presence of oxygen
(anaerobic bacteria). In children, Haemophilus influenzae type B frequently causes orbital cellulitis following a sinus infection.
Streptococcus pyogenes can be picked up from a
person who has strep throat or an infected sore. Other
cellulitis-causing bacteria can be acquired from direct
contact with infected sores. Persons who are at a higher
risk for cellulitis are those who have a severe underlying
disease (such as cancer, diabetes, and kidney disease),
are taking steroid medications, have a reduced immune
system (because of AIDS, organ transplant, etc.), have
been burned, have insect bites, have reduced blood
circulation to limbs, or have had a leg vein removed
for coronary bypass surgery. In addition, chicken pox,
human or animal bite wounds, skin wounds, and recent
surgery can put a person at a higher risk for cellulitis.
The characteristic symptoms of cellulitis are redness, warmth, pain, and swelling. The infected area
appears as a red patch that gets larger rapidly within
the first 24 hours. A thick red line which progresses
towards the heart may appear indicating an infection
of the lymph vessels (lymphangitis). Other symptoms
which may occur include fever, chills, tiredness, muscle
aches, and a general ill feeling. Some people also
experience nausea, vomiting, stiff joints, and hair loss
at the infection site.
The characteristic symptoms of orbital cellulitis
are eye pain, redness, swelling, warmth, and tenderness. The eye may bulge out and it may be difficult or
impossible to move. Temporary loss of vision, pus
drainage from the eye, chills, fever, headaches, vomiting, and a general ill feeling may occur.

Diagnosis
Cellulitis may be diagnosed and treated by a family
doctor, an infectious disease specialist, a doctor who
specializes in skin diseases (dermatologist), or in the
case of orbital cellulitis, an eye doctor (ophthalmologist). The diagnosis of cellulitis is based mainly on the
patient’s symptoms. The patient’s recent medical history is also used in the diagnosis.
Laboratory tests may be done to determine which
kind of bacteria is causing the infection but these tests
are not always successful. If the skin injury is visible, a
sterile cotton swab is used to pick up a sample from the
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Inflammation—A local, protective response to tissue injury. It is characterized by redness, warmth,
swelling, and pain.
Necrotizing fasciitis—A destructive infection
which follows severe cellulitis and involves the
deep skin and underlying tissues.
Sinuses—Air cavities found in the bones of the
head. The sinuses which are connected to the
nose are prone to infection.
This person’s lower leg is swollen and inflamed due to cellulitis. Cellulitis is a Streptococcus bacterial infection of the
skin and the tissues beneath it. The face, neck, or legs are
common sites of cellulitis. (Custom Medical Stock Photo.
Reproduced by permission.)

wound. If there is no obvious skin injury, a needle may
be used to inject a small amount of sterile salt solution
into the infected skin, and then the solution is withdrawn. The salt solution should pick up some of
the bacteria causing the infection. A blood sample
may be taken from the patient’s arm to see if bacteria
have entered the bloodstream. Also, a blood test may
be done to count the number of white blood cells in the
blood. High numbers of white blood cells suggest that
the body is trying to fight a bacterial infection.
For orbital cellulitis, the doctor may often perform a special x-ray scan called computed tomography
scan (CT). This scan enables the doctor to see the
patient’s head in cross-section to determine exactly
where the infection is and see if any damage has
occurred. A CT scan takes about 20 minutes.

Treatment
Antibiotic treatment is the only way to battle this
potentially life-threatening infection. Mild to moderate cellulitis can be treated with the following antibiotics taken every four to eight hours by mouth:


penicillins (Bicillin, Wycillin, Pen Vee, V-Cillin)



erythromycin (E-Mycin, Ery-Tab)



cephalexin (Biocef, Keflex)



cloxacillin (Tegopen)

Other medications may be recommended, such as
acetaminophen (Tylenol) or ibuprofen (Motrin, Advil)
to relieve pain, and aspirin to decrease fever.
A normally healthy person is usually not hospitalized for mild or moderate cellulitis. General treatment
GALE ENCYCLOPEDIA OF MEDICINE

measures include elevation of the infected area, rest,
and application of warm, moist compresses to the
infected area. The doctor will want to see the patient
again to make sure that the antibiotic treatment is
effective in stopping the infection.
Persons at high risk for severe cellulitis will probably be hospitalized for treatment and monitoring.
Antibiotics may be given intravenously to patients
with severe cellulitis. Complications such as deep infection, or bone or joint infections, might require surgical
drainage and a longer course of antibiotic treatment.
Extensive tissue destruction may require plastic surgery
to repair. In cases of orbital cellulitis caused by a sinus
infection, surgery may be required to drain the sinuses.

Prognosis
Over 90% of all cellulitis cases are cured after seven
to ten days of antibiotic treatment. Persons with
serious disease and/or those who are taking immunosuppressive drugs may experience a more severe form of
cellulitis which can be life threatening. Serious complications include blood poisoning (bacteria growing in the
blood stream), meningitis (brain and spinal cord infection), tissue death (necrosis), and/or lymphangitis
(infection of the lymph vessels). Severe cellulitis caused
by Streptococcus pyogenes can lead to destructive and
life-threatening necrotizing fasciitis.

Prevention
Cellulitis may be prevented by wearing appropriate protective equipment during work and sports to
avoid skin injury, cleaning cuts and skin injuries with
antiseptic soap, keeping wounds clean and protected,
watching wounds for signs of infection, taking the
entire prescribed dose of antibiotic, and maintaining
good general health. Persons with diabetes should try
to maintain good blood sugar control.
765

Cellulitis

KEY TERMS

Central nervous system depressants

Resources

KEY TERMS

PERIODICALS

Lewis, Ronald T. ‘‘Soft Tissue Infections.’’ World Journal of
Surgery 22, no. 2 (February 1998): 146-51.

Belinda Rowland, PhD

Central Mississippi Valley disease see
Histoplasmosis

I Central
nervous system
depressants
Definition
Central nervous system (CNS) depressants are
drugs that can be used to slow down brain activity.

Purpose
CNS depressants may be prescribed by a physician to treat anxiety, muscle tension, pain, insomnia,
acute stress reactions, panic attacks, and seizure disorders. In higher doses, some CNS depressants may be
used as general anesthetics.

GABA (gamma-aminobutyric acid)—A neurotransmitter that slows down the activity of nerve
cells in the brain.
Neurotransmitter—A chemical compound in the
brain that carries signals from one nerve cell to
another.

uncomfortable; for example, withdrawal from a
depressant treating insomnia or anxiety can cause
rebound insomnia or anxiety as the brain’s activity
bounces back after being suppressed. In some cases
withdrawal can result in lifethreatening seizures.
Generally, depressant withdrawal should be undertaken under a physician’s supervision. Many physicians
will reduce the depressant dosage gradually, to give
the body time to adjust. Certain CNS depressants such
as barbiturates are easy to overdose on, since there is a
relatively small difference between the optimal dose
and an overdose. A small miscalculation can lead to
coma, slowed breathing, and death. CNS depressants
should be administered to elderly individuals with
care, as these individuals have a reduced ability to
metabolize CNS depressants.

Description
Throughout history, humans have sought relief
from anxiety and insomnia by using substances that
depress brain activity and induce a drowsy or calming effect. CNS depressants include a wide range of
drugs such as alcohol, narcotics, barbiturates (Amytal,
Nembutal, Seconal), benzodiazepines (Ativan, Halcion,
Librium, Valium, Xanax), chloral hydrate, and methaqualone (Quaaludes), as well as newer CNS depressants
developed in the 1990s, such as Buspirone (Buspar) and
Zolpidem (Ambien), which are thought to have the
fewest side effects. Most CNS depressants activate a
neurotransmitter called gamma-aminobutyric acid
(GABA), which helps decrease brain activity. Street
names for CNS depressants include Reds, Yellows,
Blues, Ludes, Barbs, and Downers.

Precautions
Most CNS depressants have the potential to be
physically and psychologically addictive. Alcohol is
the most widely abused depressant. The body
tends to develop tolerance for CNS depressants, and
larger doses are needed to achieve the same effects.
Withdrawal from some CNS depressants can be
766

Side Effects
Especially when taken in excess, CNS depressants
can cause confusion and dizziness, and impair judgment, memory, intellectual performance, and motor
coordination.

Interactions
CNS depressants should be used with other medications, such as antidepressant medications, only
under a physician’s supervision. Certain herbal remedies, such as Valerian and Kava, may dangerously
exacerbate the effects of certain CNS depressants.
Also, ingesting a combination of CNS depressants,
such Valium and alcohol, for example, is not advised.
When mixed together, CNS depressants tend to
amplify each other’s effects, which can cause severely
reduced heart rate and even death.
Resources
BOOKS

Fontanarosa, P. Alternative Medicine: An Objective
Assessment. American Medical Association, 2000.
GALE ENCYCLOPEDIA OF MEDICINE

American Society of Addiction Medicine. 4601 North Park
Avenue, Arcade Suite 101, Chevy Chase, MD 20815.
(301) 656-3920. <http://www.asam.org>.
National Institute on Drug Abuse. 6001 Executive Blvd,
Bethesda, MD 20892. (301) 443-1124 <http://
www.nida.nih.gov>.

Ann Quigley

rare cases, head trauma or surgical procedures may
introduce bacteria directly into the CNS. However,
the source of infection cannot always be identified.
Specific symptoms of a CNS infection hinge on its
exact location, but may include severe headache or
back pain, weakness, sensory loss, and a fever. An
individual may report a stiff neck, nausea or vomiting,
and tiredness or disorientation. There is a potential for
seizures, paralysis, or coma.

Diagnosis

nervous system
I Central
infections
Definition
The central nervous system, or CNS, comprises
the brain, the spinal cord, and associated membranes.
Under some circumstances, bacteria may enter areas
of the CNS. If this occurs, abscesses or empyemas may
be established.

Description
In general, the CNS is well defended against infection. The spine and brain are sheathed in tough, protective membranes. The outermost membrane, the
dura mater, and the next layer, the arachnoid, entirely
encase the brain and spinal cord. However, these
defenses are not absolute. In rare cases, bacteria gain
access to areas within the CNS.
Bacterial infection of the CNS can result in
abscesses and empyemas (accumulations of pus).
Abscesses have fixed boundaries, but empyemas lack
definable shape and size. CNS infections are classified
according to the location where they occur. For example, a spinal epidural abscess is located above the dura
mater, and a cranial subdural empyema occurs
between the dura mater and the arachnoid.
As pus and other material from an infection accumulate, pressure is exerted on the brain or spinal cord.
This pressure can damage the nervous system tissue,
possibly permanently. Without treatment, a CNS
infection is fatal.

Causes and symptoms
Typically, bacterial invasion results from the
spread of a nearby infection; for example, a chronic
sinus or middle ear infection can extend beyond its
initial site. Bacteria may also be conveyed to the CNS
from distant sites of infection by the bloodstream. In
GALE ENCYCLOPEDIA OF MEDICINE

Physical symptoms, such as a fever and intense
backache or a fever, severe headache, and stiff neck,
raise the suspicion of a CNS infection. Blood tests may
indicate the presence of an infection but do not pinpoint its location. CT scans or MRI scans of the brain
and spine can provide definitive diagnosis, with an
MRI scan being the most sensitive. A lumbar puncture
and analysis of the cerebrospinal fluid can help diagnose an epidural abscess; however, the procedure can
be dangerous in cases of subdural empyema.

Treatment
A two-pronged approach is taken to treat CNS
infections. First, antibiotic therapy against an array of
potential infectious bacteria is begun. The second stage
involves surgery to drain the infected site. Although
some CNS infections have been resolved with antibiotics alone, the more aggressive approach is often preferred. Surgery allows immediate relief of pressure on
the brain or spinal cord, as well as an opportunity to
collect infectious material for bacterial identification.
Once the bacterial species is identified, drug therapy can
be altered to a more specific antibiotic. However, surgery may not be an option in some cases, such as when
there are numerous sites of infection or when infection
is located in an inaccessible area of the brain.

Prognosis
The fatality rate associated with CNS infections
ranges from 10% to as high as 40%. Some survivors
experience permanent CNS damage, resulting in partial paralysis, speech problems, or seizures. Rapid
diagnosis and treatment are essential for a good prognosis. With prompt medical attention, an individual
may recover completely.

Prevention
Treatment for pre-existing infections, such as sinus
or middle ear infections, may prevent some cases of
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Central nervous system infections

ORGANIZATIONS

Central nervous system stimulants

Purpose

KEY TERMS
Abscess—A pus-filled area with definite borders.
Arachnoid—One of the membranes that sheathes
the spinal cord and brain; the arachnoid is the
second-layer membrane.
Cerebrospinal fluid—Fluid that is normally found
in the spinal cord and brain. Abnormal levels of
certain molecules in this fluid can indicate the
presence of infection or damage to the central
nervous system.
CT scan (computed tomography)—Cross-sectional
x rays of the body are compiled to create a threedimensional image of the body’s internal structures.
Dura mater—One of the membranes that sheathes
the spinal cord and brain; the dura mater is the
outermost layer.
Empyema—A pus-filled area with indefinite borders.
Lumbar puncture—A procedure in which a needle
is inserted into the lower spine to collect a sample
of cerebrospinal fluid.
MRI (magnetic resonance imaging)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.

CNS infection. However, since some CNS infections
are of unknown origin, not all are preventable.
Resources
BOOKS

Scheld, W. M., R. J. Whitley, and D. T. Durack, editors.
Infections of the Central Nervous System. 2nd ed.
Philadelphia: Lippincott-Raven Publishers, 1997.

Julia Barrett

nervous system
I Central
stimulants
Definition
Central nervous system (CNS) stimulants are medicines that speed up physical and mental processes.
768

Central nervous system stimulants are used to
treat conditions characterized by lack of adrenergic
stimulation, including narcolepsy and neonatal
apnea. Additionally, methylphenidate (Ritalin) and
dextroamphetamine sulfate (Dexedrine) are used for
their paradoxical effect in attention–deficit hyperactivity disorder (ADHD).
The anerexiants, benzphetamine (Didrex), diethylpropion (Tenuate), phendimetrazine (Bontril, Plegine),
phentermine (Fastin, Ionamine), and sibutramine
(Meridia) are CNS stimulants used for appetite reduction in severe obesity. Although these drugs are structurally similar to amphetamine, they cause less sensation
of stimulation, and are less suited for use in conditions
characterized by lack of adrenergic stimulation.
Phenylpropanolamine and ephedrine have been
used both as diet aids and as vasoconstrictors.

Description
The majority of CNS stimulants are chemically
similar to the neurohormone norepinephrine, and simulate the traditional ‘‘fight or flight’’ syndrome associated with sympathetic nervous system arousal.
Caffeine is more closely related to the xanthines, such
as theophylline. A small number of additional members
of the CNS stimulant class do not fall into specific
chemical groups.

Precautions
Amphetamines have a high potential for abuse.
They should be used in weight reduction programs
only when alternative therapies have been ineffective.
Administration for prolonged periods may lead to
drug dependence. These drugs are classified as schedule II under federal drug control regulations.
The amphetamines and their cogeners are contraindicated in advanced arteriosclerosis, symptomatic
cardiovascular disease, and moderate to severe hypertension and hyperthyroidism. They should not be used
to treat patients with hypersensitivity or idiosyncrasy
to the sympathomimetic amines, or with glaucoma, a
history of agitated states, a history of drug abuse, or
during the 14 days following administration of monoamine oxidase (MAO) inhibitors.
Methylphenidate may lower the seizure threshold.
Benzphetamine is category X during pregnancy.
Diethylpropion is category B. Other anorexiants have
not been rated; however their use during pregnancy
GALE ENCYCLOPEDIA OF MEDICINE

Agranulocytosis—Anacute febrilecondition marked
by severe depression of the granulocyte-producing
bone marrow, and by prostration, chills, swollen
neck, and sore throat sometimes with local ulceration.
Anorexiant—A drug that suppresses appetite.
Anxiety—Worry or tension in response to real or imagined stress, danger, or dreaded situations. Physical
reactions, such as fast pulse, sweating, trembling,
fatigue, and weakness, may accompany anxiety.
Attention-deficit hyperactivity disorder (ADHD)—
A condition in which a person (usually a child) has
an unusually high activity level and a short attention
span. People with the disorder may act impulsively
and may have learning and behavioral problems.

is not recommended because the infant may experience withdrawal symptoms.
There have been reports that when used in children, methylphenidate and amphetamines may retard
growth. Although these reports have been questioned,
it may be suggested that the drugs not be administered
outside of school hours (because most children have
behavior problems in school), in order to permit full
stature to be attained.
The most common adverse effects of CNS stimulants are associated with their primary action. Typical
responses include overstimulation, dizziness, restlessness, and similar reactions. Rarely, hematologic reactions, including leukopenia, agranulocytosis, and
bone marrow depression have been reported.
Lowering of the seizure threshold has been noted
with most drugs in this class.

Central nervous system—The brain and spinal cord.
Depression—A mental condition in which people
feel extremely sad and lose interest in life. People
with depression may also have sleep problems and
loss of appetite, and may have trouble concentrating and carrying out everyday activities.
Leukopenia—A condition in which the number of
leukocytes circulating in the blood is abnormally
low and which is most commonly due to a
decreased production of new cells in conjunction
with various infectious diseases or as a reaction to
various drugs or other chemicals.
Pregnancy category—A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B: Animal
studies indicate no fetal risk, but no human studies, or
adverse effects in animals, but not in well-controlled
human studies. Category C: No adequate human or
animal studies, or adverse fetal effects in animal studies, but no available human data. Category D:
Evidence of fetal risk, but benefits outweigh risks.
Category X: Evidence of fetal risk. Risks outweigh
any benefits.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug on which he or she has
become dependent.

does not appear to be advisable. Safety for use of
anorexiants has not been evaluated.
Amphetamines are all category C during pregnancy. Breastfeeding while receiving amphetamines
GALE ENCYCLOPEDIA OF MEDICINE

Withdrawal syndrome
Abrupt discontinuation following prolonged high
dosage results in extreme fatigue, mental depression
and changes on the sleep EEG. This response is most
evident with amphetamines, but may be observed with
all CNS stimulants taken over a prolonged period of
time.
Nancy Ross-Flanigan

Central retinal artery occlusion see
Retinopathies
Central retinal vein occlusion see
Retinopathies

I Cephalosporins
Definition
Cephalosporins are medicines that kill bacteria or
prevent their growth.

Purpose
Cephalosporins are used to treat infections in different parts of the body—the ears, nose, throat, lungs,
sinuses, and skin, for example. Physicians may prescribe these drugs to treat pneumonia, strep throat,
staph infections, tonsillitis, bronchitis, and gonorrhea.
These drugs will not work for colds, flu, and other
infections caused by viruses.
769

Cephalosporins

KEY TERMS

Cephalosporins

Cephalosporins are a newer class of antibiotics
and often are seen as an alternative to penicillin for
many patients. Clinical studies continue to compare
this class of antibiotics to penicillin in combating
various infections. For example, a 2004 study showed
that cephalosporins are three times more effective
than penicillin for treating bacterial throat infections,
such as strep throat, in children. The authors recommended cephalosporin drugs as the first choices for
pediatricians.

Description
Examples of cephalosporins are cefaclor (Ceclor),
cefadroxil (Duricef), cefazolin (Ancef, Kefzol,
Zolicef), cefixime, (Suprax), cefoxitin (Mefoxin), cefprozil (Cefzil), ceftazidime (Ceptaz, Fortaz, Tazicef,
Tazideme), cefuroxime (Ceftin) and cephalexin
(Keflex). These medicines are available only with a
physician’s prescription. They are sold in tablet, capsule, liquid, and injectable forms.

Recommended dosage
The recommended dosage depends on the type of
cephalosporin. The physician who prescribed the drug
or the pharmacist who filled the prescription can
recommend the correct dosage.
Cephalosporins always should be taken exactly as
directed by the physician. Patients never should take
larger, smaller, more frequent, or less frequent doses.
The drug should be taken for exactly as long as directed, no more and no less. Patients should not save
some doses of the drug to take for future infections.
The medicine may not be right for other kinds of
infections, even if the symptoms are the same. In addition, patients should take all of the medicine to treat
the infection for which it was prescribed. The infection
may not clear up completely if too little medicine is
taken. Taking this medicine for too long, on the other
hand, may open the door to new infections that do not
respond to the drug.
Some cephalosporins work best when taken on an
empty stomach. Others should be taken after meals.
The physician who prescribed the medicine or the
pharmacist who filled the prescription can provide
instructions on how to take the medicine.

flushing, and other symptoms may result within 15–30
minutes and may last for several hours. Alcoholic beverages or other medicines that contain alcohol should
not be used while being treated with cephalosporins and
for several days after treatment ends.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if they
take cephalosporins. Before taking these drugs, the
physician should be told about any of these conditions:
ALLERGIES. Severe allergic reactions to this medicine may occur. Anyone who is allergic to cephalosporins of any kind should not take other cephalosporins.
Anyone who is allergic to penicillin should check with a
physician before taking any cephalosporin. The physician should also be told about allergies to foods, dyes,
preservatives, or other substances.
DIABETES. Some cephalosporins may cause false
positive results on urine sugar tests for diabetes.
People with diabetes should check with their physicians to see if they need to adjust their medication or
their diets.
PHENYLKETONURIA. Oral suspensions of cefprozil
contain phenylalanine. People with phenylketonuria
(PKU) should consult a physician before taking this
medicine.
PREGNANCY. Women who are pregnant or who
may become pregnant should check with their physicians before using cephalosporins.
BREASTFEEDING. Cephalosporins may pass into
breast milk and may affect nursing babies. Women
who are breastfeeding and who need to take this medicine should check with their physicians. They may
need to stop breastfeeding until treatment is finished.
OTHER MEDICAL CONDITIONS. Before using
cephalosporins, people with any of these medical problems should make sure their physicians are aware of
their conditions:


History of stomach or intestinal problems, especially
colitis. Cephalosporins may cause colitis in some
people.



Kidney problems. The dose of cephalosporin may
need to be lowered.



Bleeding problems. Cephalosporins may increase the
chance of bleeding in people with a history of bleeding problems.



Liver disease. The dose of cephalosporin may need to
be lowered.

Precautions
Certain cephalosporins should not be combined
with alcohol or with medicines that contain alcohol.
Abdominal or stomach cramps, nausea, vomiting, facial
770

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Side effects
Medical attention should be sought immediately
if any of these symptoms develop while taking
cephalosporins:


shortness of breath



pounding heartbeat



skin rash or hives



severe cramps or pain in the stomach or abdomen



fever



Severe watery or bloody diarrhea (may occur up to
several weeks after stopping the drug)



unusual bleeding or bruising.

Other rare side effects may occur. Anyone who
has unusual symptoms during or after treatment with
cephalosporins should get in touch with his or her
physician

Interactions
Some cephalosporins cause diarrhea. Certain
diarrhea medicines, such as diphenoxylate-atropine
(Lomotil), may make the problem worse. A physician
should be consulted before taking any medicine for
diarrhea caused by taking cephalosporins.
Birth control pills may not work properly
when taken at the same time as cephalosporins. To
prevent pregnancy, other methods of birth control
should be used in addition to the pills while taking
cephalosporins.
Taking cephalosporins with certain other drugs
may increase the risk of excess bleeding. Among the
drugs that may have this effect when taken with cephalosporins are:

KEY TERMS
Bronchitis—Inflammation of the air passages of the
lungs.
Colitis—Inflammation of the colon (large bowel).
Gonorrhea—A sexually transmitted disease (STD)
that causes infection in the genital organs and may
cause disease in other parts of the body.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or
illness.
Phenylketonuria (PKU)—A genetic disorder in
which the body lacks an important enzyme. If
untreated, the disorder can lead to brain damage
and mental retardation.
Pneumonia—A disease in which the lungs become
inflamed. Pneumonia may be caused by bacteria,
viruses, or other organisms, or by physical or chemical irritants.
Sexually transmitted disease—A disease that is
passed from one person to another through sexual
intercourse or other intimate sexual contact. Also
called STD.
Staph infection—Infection with Staphylococcus
bacteria. These bacteria can infect any part of the
body.
Strep throat—A sore throat caused by infection
with Streptococcus bacteria. Symptoms include
sore throat, chills, fever, and swollen lymph
nodes in the neck.
Tonsillitis—Inflammation of a tonsil, a small mass
of tissue in the throat.

may be greater. Anyone who takes cephalosporins
should let the physician know all other medicines he
or she is taking.



blood thinning drugs (anticoagulants) such as warfarin (Coumadin)

Resources



blood viscosity reducing medicines such as pentoxifylline (Trental)

‘‘Newer Antibiotics Better for Throats’’ Pulse April 12,
2004: 18.



the antiseizure medicines divalproex (Depakote) and
valproic acid (Depakene)

Cephalosporins may also interact with other medicines. When this happens, the effects of one or both
of the drugs may change or the risk of side effects

GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Nancy Ross-Flanigan
Teresa G. Odle

Cerebral abscess see Brain abscess

771

Cephalosporins

USE OF CERTAIN MEDICINES. Taking cephalosporins with certain other drugs may affect the way
the drugs work or may increase the chance of side
effects.

Cerebral amyloid angiopathy

I Cerebral amyloid angiopathy
Definition
Cerebral amyloid angiopathy (CAA) is also
known as congophilic angiopathy or cerebrovascular
amyloidosis. It is a disease of small blood vessels in the
brain in which deposits of amyloid protein in the vessel
walls may lead to stroke, brain hemorrhage, or dementia. Amyloid protein resembles a starch and is deposited in tissues during the course of certain chronic
diseases.

Description
CAA may affect patients over age 45, but is most
common in patients over age 65, and becomes more
common with increasing age. Men and women are
equally affected. In some cases, CAA is sporadic but
it may also be inherited as an autosomal dominant
condition (a form of inheritance in which only one
copy of a gene coding for a disease need be present
for that disease to be expressed; if either parent has the
disease, a child has a 50% chance of inheriting the
disease). CAA is responsible for 5–20% of brain
hemorrhage, and up to 30% of lobar hemorrhages
localized to one lobe of the brain. CAA may be
found during an autopsy in over one-third of persons
over age 60, even though they may not have had brain
hemorrhage, stroke, or other manifestations of the
disease during life. In Alzheimer’s disease, CAA is
more common than in the general population, and
may occur in more than 80% of patients over age 60.

Causes and symptoms
The cause of amyloid deposits in blood vessels in
the brain in sporadic CAA is not known. In hereditary
CAA, genetic defects, typically on chromosome 21,
allow accumulation of amyloid, a protein made up of
units called beta-pleated sheet fibrils. The fibrils tend
to clump together, so that the amyloid cannot be dissolved and builds up in the brain blood vessel walls.
One form of amyloid fibril subunit proteins is the
amyloid beta protein.
Different theories have been suggested for the
source of amyloid beta protein in the brain. The systemic theory suggests that amyloid beta protein in
the blood stream is deposited in blood vessels in the
brain, causing weakness in the blood vessel wall and
breakdown in the blood-brain barrier. Normally, the
blood-brain barrier keeps proteins and other large
molecules from escaping from the blood vessel to the
772

brain tissue. When there is breakdown of the bloodbrain barrier, amyloid beta protein leaks through the
blood vessel wall, and is deposited in the brain substance, where it forms an abnormal structure called a
neuritic plaque.
A second, more likely theory is that amyloid
fibrils that form amyloid beta protein are produced
by perivascular microglia, or support cells in contact
with the brain blood vessel wall. The third theory is
that the brain tissue gives rise to amyloid beta protein.
Both the nerve cells and the glia are known to produce
amyloid precursor protein, which increases with aging
and with cell stress.
Bleeding into the brain may occur as tiny blood
vessels carrying amyloid deposits become heavier and
more brittle, and are therefore more likely to burst
with minor trauma or with fluctuating blood pressure.
Aneurysms, or ballooning of the blood vessel wall,
may develop, and may also rupture as the stretched
wall becomes thinner and is under more pressure.
Amyloid deposits may destroy smooth muscle cells
or cause inflammation in the blood vessel wall. This
may also cause the blood vessel to break more easily.
The most common form of CAA is the sporadic
form associated with aging. This type of CAA usually
causes lobar hemorrhage, which may recur in different
lobes of the brain. The frontal lobe (behind the forehead) and parietal lobe (behind the frontal lobe) are
most often affected; the temporal lobe (near the temple) and occipital lobe (at the back of the brain) are
affected less often; and the cerebellum (under the occipital lobe) is rarely affected. Approximately 10–50%
of hemorrhages in sporadic CAA involve more than
one lobe.
Symptoms of lobar hemorrhage in CAA include
sudden onset of headache, neurologic symptoms such
as weakness, sensory loss, visual changes, or speech
problems, depending on which lobe is involved; and
decreased level of consciousness (a patient who is
difficult to arouse), nausea, and vomiting. Sporadic
CAA may be associated with symptoms unrelated to
lobar hemorrhage. Petechial hemorrhages (tiny
hemorrhages involving many small vessels) may produce recurrent, brief neurologic symptoms secondary
to seizures or decreased blood flow, or may produce
rapidly progressive dementia (loss of memory and
other brain functions) that worsens in distinct steps
rather than gradually. Over 40% of patients with
hemorrhage secondary to CAA also have dementia.
Genetic factors play a role in certain types of CAA
and in diseases associated with CAA:
GALE ENCYCLOPEDIA OF MEDICINE

Dutch type of hereditary cerebral hemorrhage with
amyloidosis (build up of amyloid protein in blood
vessels): autosomal dominant, with a genetic mutation involving the amyloid precursor protein. Onset
is at age 40–60 with headaches, brain hemorrhage
often in the parietal lobe, strokes, and dementia.
More than half of patients die from their first hemorrhage. Patients with the Dutch type of CAA may
produce an abnormal anticoagulant, or blood thinner, which makes hemorrhage more likely.



Flemish type of hereditary cerebral hemorrhage with
amyloidosis: autosomal dominant, with a mutation
involving the amyloid precursor protein. Symptoms
include brain hemorrhage or dementia.



Familial Alzheimer’s disease: autosomal dominant,
comprising 5–10% of all Alzheimer’s disease cases
(a brain disease in which death of nerve cells leads to
progressive dementia).



Down Syndrome: caused by trisomy 21 (three rather
than two copies of chromosome 21), causing excess
amyloid precursor protein gene. Children with
Down syndrome are mentally handicapped and
may have heart problems.



Icelandic type of hereditary cerebral hemorrhage
with amyloidosis: autosomal dominant, with mutation in the gene coding for cystatin C. Symptoms
often begin at age 30–40 with multiple brain hemorrhages, dementia, paralysis (weakness), and death in
10–20 years. Headache occurs in more than half of
patients, and seizures occur in one-quarter. Unlike
most other forms of CAA, most hemorrhages
involve the basal ganglia deep within the brain.
(Basal ganglia are islands of tissues in the cerebellum
part of the brain.)





Familial oculo-leptomeningeal amyloidosis: autosomal dominant with unknown gene defect(s), described
in Japanese, Italian, and North American families.
Symptoms can include dementia, ataxia (problems
with coordination), spasticity (limb stiffness), strokes,
seizures, peripheral neuropathy (disease affecting the
nerves supplying the limbs), migraine, spinal cord problems, blindness, and deafness. Brain hemorrhage is
rare as the amyloid protein is deposited in blood vessels
in the eye and meninges (brain coverings), but not in
the brain itself. In Italian families with the disease,
patients may be affected as early as 20–30 years of age.
British type of familial amyloidosis: autosomal
dominant with unknown gene defect(s), associated
with progressive dementia, spasticity, and ataxia.
Brain stem, spinal cord, and cerebellum all exhibit
amyloid deposits, but hemorrhage typically does not
occur.

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
As in most neurologic diseases, diagnosis is made
most often from the patient’s history, with careful
inquiry into family history and the patient’s onset
and pattern of symptoms, as well as neurologic examination. Brain computed tomography scan (CT) or
magnetic resonance imaging (MRI) may identify
lobar hemorrhage, stroke, or petechial hemorrhages,
and are important in excluding arteriovenous malformation, brain tumor, or other causes of hemorrhage.
Angiography (x-ray study of the interior of blood vessels and the heart) is not helpful in diagnosis of CAA,
but may be needed to exclude aneurysm. Brain biopsy
(surgical removal of a small piece of brain tissue) may
show characteristic amyloid deposits, but is rarely
performed, as the risk may not be justifiable in the
absence of effective treatment for CAA. If diagnosis is
uncertain, biopsy may be needed to rule out conditions
which are potentially treatable. Definite diagnosis
requires microscopic examination of brain tissue,
either at biopsy, at autopsy, or at surgery when brain
hemorrhage is drained. Lumbar puncture to examine
cerebrospinal fluid proteins may show characteristic
abnormalities, but is not part of the routine exam. In
familial forms, genetic analysis may be helpful.
CAA with hemorrhage must be distinguished from
other types of brain hemorrhage. In CAA, hemorrhage
typically occurs in the lobar region, often ruptures
into the subarachnoid space between the brain and its
coverings, and occurs at night. In hemorrhage related
to high blood pressure, hemorrhage is usually deeper
within the brain, ruptures into the ventricles or cavities
deep inside the brain, and occurs during daytime
activities. Other causes of brain hemorrhage are arteriovenous malformations, trauma, aneurysms, bleeding
into a brain tumor, vasculitis (inflammation of blood
vessels), or bleeding disorders.

Treatment
Although there is no effective treatment for the
underlying disease process of CAA, measures can be
taken to prevent brain hemorrhage in patients diagnosed with CAA. High blood pressure should be treated aggressively, and even normal blood pressure can
be lowered as much as tolerated without side effects
from medications. Blood thinners such as Coumadin,
antiplatelet agents such as aspirin, or medications
designed to dissolve blood clots may cause hemorrhage
in patients with CAA, and should be avoided if possible. If these medications are required for other conditions, such as heart disease, the potential benefits must
be carefully weighed against the increased risks.
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Cerebral amyloid angiopathy



Cerebral aneurysm

KEY TERMS
Amyloid—Amyloid protein resembles a starch and
is deposited in tissues during the course of certain
chronic diseases.
Ataxia—Problems with coordination and walking.
Autosomal dominant—A form of inheritance in
which only one copy of a gene coding for a disease
need be present for that disease to be expressed. If
either parent has the disease, a child has a 50%
chance of inheriting the disease.
Chromosome—A cellular structure containing
genetic information in the form of DNA.
Dementia—Loss of memory and other higher functions, such as thinking or speech, lasting six months
or more.
Hemorrhage—Bleeding, or escape of blood
through ruptured or unruptured blood vessel walls.
Lobar hemorrhage—Bleeding into one of the lobes
of the brain.
Seizure—Epileptic convulsion, fit, or attack.
Sporadic—A form of disease found in persons without a family history of the disease.
Spasticity—Limb stiffness related to disease of the
brain or spinal cord.
Stroke—Sudden neurological deficit related to
impaired blood supply to the brain.

Seizures, or recurrent neurologic symptoms
thought to be seizures, should be treated with antiepileptic drugs, although Depakote (sodium valproate) should be avoided because of its antiplatelet
effect. Anti-epileptic drugs are sometimes given to
patients with large lobar hemorrhage in an attempt
to prevent seizures, although the benefit of this is
unclear.
Once brain hemorrhage has occurred, the patient
should be admitted to a hospital (ICU) for neurologic
monitoring and control of increased pressure within
the brain, blood pressure control, and supportive
medical care. Antiplatelet agents and blood thinners
should be discontinued and their effects reversed, if
possible. Surgery may be needed to remove brain
hemorrhage, although bleeding during surgery may
be difficult to control.
CAA may be rarely associated with cerebral vasculitis, or inflammation of the blood vessel walls. In
774

these cases treatment with steroids or immune system
suppressants may be helpful. Without tissue examination, vasculitis cannot be diagnosed reliably, and
probably coexists with CAA too rarely to justify steroid treatment in most cases.

Prognosis
Since CAA is associated with progressive blood
vessel degeneration, and since there is no effective
treatment, most patients have a poor prognosis.
Aggressive neurosurgical management allows
increased survival following lobar hemorrhage, but
as of 1998, 20–90% of patients die from the first
hemorrhage or its complications, which include progression of hemorrhage, brain edema (swelling) with
herniation (downward pressure on vital brain structures), seizures, and infections such as pneumonia.
Many survivors have persistent neurologic deficits
related to the brain lobe affected by hemorrhage, and
are at risk for additional hemorrhages, seizures, and
dementia. Prognosis is worse in patients who are older,
or who have larger hemorrhages or recurrent hemorrhages within a short time.
Resources
PERIODICALS

Neau, J. P., et.al. ‘‘Recurrent Intracerebral Hemorrhage.’’
Neurology 49, no. 1 (1997): 106-113.

Laurie Barclay, MD

I Cerebral aneurysm
Definition
A cerebral aneurysm occurs at a weak point in the
wall of a blood vessel (artery) that supplies blood to
the brain. Because of the flaw, the artery wall bulges
outward and fills with blood. This bulge is called an
aneurysm. An aneurysm can rupture, spilling blood
into the surrounding body tissue. A ruptured cerebral
aneurysm can cause permanent brain damage, disability, or death.

Description
A cerebral aneurysm can occur anywhere in the
brain. Aneurysms can have several shapes. The saccular aneurysm, once called a berry aneurysm, resembles
a piece of fruit dangling from a branch. Saccular
GALE ENCYCLOPEDIA OF MEDICINE

The greatest danger of aneurysms is rupture.
Approximately 50–75% of stricken people survive an
aneurysmal rupture. A ruptured aneurysm spills blood
into the brain or into the fluid-filled area that surrounds the brain tissue. Bleeding into this area, called
the subarachnoid space, is referred to as subarachnoid
hemorrhage (SAH). About 25,000 people suffer a SAH
each year. It is estimated that people with unruptured
aneurysm have an annual 1–2% risk of hemorrhage.
Under age 40, more men experience SAH. After age
40, more women than men are affected.
Most people who have suffered a SAH from a
ruptured aneurysm did not know that the aneurysm
even existed. Based on autopsy studies, medical
researchers estimate that 1–5% of the population has
some type of cerebral aneurysm. Aneurysms rarely
occur in the very young or the very old; about 60%
of aneurysms are diagnosed in people between ages 40
and 65.
Some aneurysms may have a genetic link and run
in families. The genetic link has not been completely
proven and a pattern of inheritance has not been
determined. Some studies seem to show that firstdegree relatives of people who suffered aneurysmal
SAH are more likely to have aneurysms themselves.
These studies reported that such immediate family
members were four times more likely to have aneurysms than the general population. Other studies do
not confirm these findings. Better evidence links
aneurysms to certain rare diseases of the connective
tissue. These diseases include Marfan syndrome, pseudoxanthoma elasticum, Ehlers-Danlos syndrome, and
fibromuscular dysplasia. Polycystic kidney disease is
also associated with cerebral aneurysms.
These diseases are also associated with an
increased risk of aneurysmal rupture. Certain other
conditions raise the risk of rupture, too. Most aneurysms that rupture are a half-inch or larger in diameter.
Size is not the only factor, however, because smaller
aneurysms also rupture. Cigarette smoking, excessive
alcohol consumption, and recreational drug use (for
example, use of cocaine) have been linked with an
increased risk. The role, if any, of high blood pressure
has not been determined. Some studies have implicated high blood pressure in aneurysm formation
GALE ENCYCLOPEDIA OF MEDICINE

and rupture, but people with normal blood pressure
also experience aneurysms and SAHs. High blood
pressure may be a risk factor but not the most important one. Pregnancy, labor, and delivery also seem to
increase the possibility that an aneurysm might rupture, but not all doctors agree. Physical exertion and
use of oral contraceptives are not suspected causes for
aneurysmal rupture.

Causes and symptoms
Cerebral aneurysms can be caused by brain
trauma, infection, hardening of the arteries (atherosclerosis), or abnormal rapid cell growth (neoplastic
disease), but most seem to arise from a congenital, or
developmental, defect. These congenital aneurysms
occur more frequently in women. Whatever the cause
may be, the inner wall of the blood vessel is abnormally thin and the pressure of the blood flow causes an
aneurysm to form.
Most aneurysms go unnoticed until they rupture.
However, 10–15% of unruptured cerebral aneurysms
are found because of their size or their location.
Common warning signs include symptoms that affect
only one eye, such as an enlarged pupil, a drooping
eyelid, or pain above or behind the eye. Other symptoms are a localized headache, unsteady gait, a temporary problem with sight, double vision, or numbness
in the face.
Some aneurysms bleed occasionally without rupturing. Symptoms of such an aneurysm develop gradually. The symptoms include headache, nausea,
vomiting, neck pain, black-outs, ringing in the ears,
dizziness, or seeing spots.
Eighty to ninety percent of aneurysms are not
diagnosed until after they have ruptured. Rupture is
not always a sudden event. Nearly 50% of patients
who have aneurysmal SAHs also experience ‘‘the
warning leak phenomenon.’’ Persons with warning
leak symptoms have sudden, atypical headaches that
occur days or weeks before the actual rupture. These
headaches are referred to as sentinel headaches.
Nausea, vomiting, and dizziness may accompany sentinel headaches. Unfortunately, these symptoms can
be confused with tension headaches or migraines, and
treatment can be delayed until rupture occurs.
When an aneurysm ruptures, most victims experience a sudden, extremely severe headache. This headache is typically described as the worst headache of the
victim’s life. Nausea and vomiting commonly accompany the headache. The person may experience a short
loss of consciousness or prolonged coma. Other
775

Cerebral aneurysm

aneurysms are usually found at a branch in the blood
vessel where they balloon out by a thin neck. Saccular
cerebral aneurysms most often occur at the branch
points of large arteries at the base of the brain.
Aneurysms may also take the form of a bulge in one
wall of the artery–a lateral aneurysm–or a widening of
the entire artery–a fusiform aneurysm.

Cerebral aneurysm
Three aneurysms can be seen in this section of a cerebral artery removed from a human brain. (Photograph by Martin Rotker,
Phototake NYC. Reproduced by permission.)

common signs of a SAH include a stiff neck, fever, and
a sensitivity to light. About 25% of victims experience
neurological problems linked to specific areas of the
brain, swelling of the brain due to fluid accumulation
(hydrocephalus), or seizure.

Diagnosis
Based on the clinical symptoms, a doctor will run
several tests to confirm an aneurysm or an SAH.
A computed tomography scan (CT) of the head is the
initial procedure. A magnetic resonance imaging test
(MRI) may be done instead of a CT scan. MRI, however, is not as sensitive as CT for detecting subarachnoid blood. A CT scan can determine whether there has
been a hemorrhage and can assist in pinpointing the
location of the aneurysm. The scan is most useful when
it is done within 72 hours of the rupture. Later scans
may miss the signs of hemorrhage.
If the CT scan is negative for a hemorrhage or
provides an unclear diagnosis, the doctor will order a
cerebrospinal fluid (CSF) analysis, also called a lumbar
puncture. In this procedure, a small amount of
776

cerebrospinal fluid is removed from the lower back
and examined for traces of blood and blood-breakdown
products. If this test is positive, cerebral angiography is
used to map the brain’s blood vessels and the damaged
area. The angiography is done to pinpoint the aneurysm’s location. About 15% of people who experience
SAH have more than one aneurysm. For this reason,
angiography should include both the common carotid
artery that feeds the front of the brain and the vertebral
artery that feeds the base of the brain. Occasionally, the
angiography fails to find the aneurysm and must be
repeated. If seizures occur, electroencephalography
(EEG) may be used to measure the electrical activity of
the brain.

Treatment
Unruptured aneurysm
If an aneurysm has not ruptured and is not causing any symptoms, it may be left untreated. Because
there is a 1–2% chance of rupture per year, the cumulative risk over a number of years may justify surgical
treatment. However, if the aneurysm is small or in a
GALE ENCYCLOPEDIA OF MEDICINE

Ruptured aneurysm
The primary treatment for a ruptured aneurysm
involves stabilizing the victim’s condition, treating the
immediate symptoms, and promptly assessing further
treatment options, especially surgical procedures. The
patient may require mechanical ventilation, oxygen,
and fluids. Medications may be given to prevent major
secondary complications such as seizures, rebleeding,
and vasospasm (narrowing of the affected blood vessel). Vasospasm decreases blood flow to the brain and
causes the death of nerve cells. A drug such as nimodipine (Nimotop) may help prevent vasospasm by
relaxing the smooth muscle tissue of the arteries.
Even with treatment, however, vasospasm may cause
stroke or death.
To prevent further hemorrhage from the aneurysm, it must be removed from circulation. In general,
surgical procedures should be performed as soon as
possible to prevent rebleeding. The chances that aneurysm will rebleed are greatest in the first 24 hours, and
vasospasm usually does not occur until 72 hours or
more after rupture. If the patient is in poor condition
or if there is vasospasm or other complication, surgical
procedures may be delayed. The preferred surgical
method is a clip ligation in which a clip is placed around
the base of the aneurysm to block it off from circulation. Surgical coating, wrapping, or trapping of the
aneurysm may also be performed. These procedures
do not completely remove the aneurysm from circulation, however, and there is some risk that it may rebleed
in the future. Newer techniques that look promising
include balloon embolization, a procedure that blocks
the aneurysm with an inflatable membrane introduced
by means of a catheter inserted through the artery.

Prognosis
An unruptured aneurysm may not cause any
symptoms over an entire lifetime. Surgical clip ligation
will ensure that it won’t rupture, but it may be better to
leave the aneurysm alone in some cases. Familial cerebral aneurysms may rupture earlier than those without
a genetic link.
The outlook is not as good for a person who
suffers a ruptured aneurysm. Fifteen to twenty-five
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Congenital—Existing at birth.
Ehlers-Danlos syndrome—A rare inheritable disease of the connective tissue marked by very elastic
skin, very loose joints, and very fragile body tissue.
Embolization—A technique to stop or prevent
hemorrhage by introducing a foreign mass, such
as an air-filled membrane (balloon), into a blood
vessel to block the flow of blood.
Fibromuscular dysplasia—A disorder that causes
unexplained narrowing of arteries and high blood
pressure.
Magnetic resonance angiography—A noninvasive
diagnostic technique that uses radio waves to map
the internal anatomy of the blood vessels.
Marfan syndrome—An inheritable disorder that
affects the skeleton, joints, and blood vessels.
Major indicators are excessively long arms and
legs, lax joints, and vascular defects.
Nimodipine (Nimotop)—A calcium-channel
blocker, that is, a drug that relaxes arterial smooth
muscle by slowing the movement of calcium
across cell walls.
Polycystic kidney disease—An abnormal condition in which the kidneys are enlarged and contain
many cysts.
Pseudoxanthoma elasticum—A hereditary disorder
of the connective, or elastic, tissue marked by premature aging and breakdown of the skin and degeneration of the arteries that leads to hemorrhages.
Subarachnoid hemorrhage (SAH)—Loss of blood
into the subarachnoid space, the fluid-filled area
that surrounds the brain tissue.
Vasospasm—Narrowing of a blood vessel caused
by a spasm of the smooth muscle of the vessel wall.

percent of people who experience a ruptured aneurysm
do not survive. An additional 25–50% die as a result of
complications associated with the hemorrhage. Of the
survivors, 15–50% suffer permanent brain damage
and disability. These conditions are caused by the
death of nerve cells. Nerve cells can be destroyed by
the hemorrhage itself or by complications from the
hemorrhage, such as vasospasm or hydrocephalus.
Hydrocephalus, a dilatation (expansion) of the fluidfilled cavity surrounding the brain, occurs in about
15% of cases. Immediate medical treatment is vital
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Cerebral aneurysm

place that would be difficult to reach, or if the person
who has the aneurysm is in poor health, the surgical
treatment may be a greater risk than the aneurysm.
Risk of rupture is higher for people who have more
than one aneurysm. Unruptured aneurysm would
probably be treated with a surgical procedure called
the clip ligation, as described below.

Cerebral palsy

to prevent further complications and brain damage in
those who survive the initial rupture. Patients who
survive SAH and aneurysm clipping are unlikely to
die from events related to SAH.

Prevention
There are no known methods to prevent an aneurysm from forming. If an aneurysm is discovered before
it ruptures, it may be surgically removed. CT or MRI
angiography may be recommended for relatives of
patients with familial cerebral aneurysms.
Resources
ORGANIZATIONS

Brain Aneurysm Foundation, Inc. 66 Canal St., Boston, MA
02114. (617) 723-3870. <http://neurosurgery.mgh.
harvard.edu/baf>.
OTHER

Bernadini, Gary L. ‘‘Intracerebral Aneurysms.’’ Columbia
University Health Sciences Page.
<http://cpmcnet.columbia.edu>.
‘‘The Brain Aneurysm Report.’’ Neurosurgical Service Page.
Harvard Medical School. <http://neurosurgery.mgh.
harvard.edu/abta/primer.htm>.

Julia Barrett

Cerebral angiography see Angiography

I Cerebral palsy
Definition
Cerebral palsy (CP) is the term used for a group of
nonprogressive disorders of movement and posture
caused by abnormal development of, or damage to,
motor control centers of the brain. CP is caused by
events before, during, or after birth. The abnormalities
of muscle control that define CP are often accompanied by other neurological and physical abnormalities.

Description
Voluntary movement (walking, grasping, chewing, etc.) is primarily accomplished using muscles
that are attached to bones, known as the skeletal
muscles. Control of the skeletal muscles originates in
the cerebral cortex, the largest portion of the brain.
Palsy means paralysis, but may also be used to
describe uncontrolled muscle movement. Therefore,
cerebral palsy encompasses any disorder of abnormal
778

movement and paralysis caused by abnormal function
of the cerebral cortex. In truth, however, CP does not
include conditions due to progressive disease or degeneration of the brain. For this reason, CP is also
referred to as static (nonprogressive) encephalopathy
(disease of the brain). Also excluded from CP are any
disorders of muscle control that arise in the muscles
themselves and/or in the peripheral nervous system
(nerves outside the brain and spinal cord).
CP is not a specific diagnosis, but is more accurately considered a description of a broad but defined
group of neurological and physical problems.
The symptoms of CP and their severity are quite
variable. Those with CP may have only minor difficulty with fine motor skills, such as grasping and
manipulating items with their hands. A severe form
of CP could involve significant muscle problems in all
four limbs, mental retardation, seizures, and difficulties with vision, speech, and hearing.
Muscles that receive defective messages from the
brain may be constantly contracted and tight (spastic),
exhibit involuntary writhing movements (athetosis),
or have difficulty with voluntary movement (dyskinesia). There can also be a lack of balance and coordination with unsteady movements (ataxia). A combination
of any of these problems may also occur. Spastic CP
and mixed CP constitute the majority of cases. Effects
on the muscles can range from mild weakness or partial
paralysis (paresis), to complete loss of voluntary control of a muscle or group of muscles (plegia). CP is also
designated by the number of limbs affected. For
instance, affected muscles in one limb is monoplegia,
both arms or both legs is diplegia, both limbs on one
side of the body is hemiplegia, and in all four limbs is
quadriplegia. Muscles of the trunk, neck, and head may
be affected as well.
CP can be caused by a number of different
mechanisms at various times—from several weeks
after conception, through birth, to early childhood.
For many years, it was accepted that most cases of
CP were due to brain injuries received during a traumatic birth, known as birth asphyxia. However, extensive research in the 1980s showed that only 5–10%
of CP can be attributed to birth trauma. Other possible causes include abnormal development of the
brain, prenatal factors that directly or indirectly
damage neurons in the developing brain, premature
birth, and brain injuries that occur in the first few
years of life.
Advances in the medical care of premature infants
in the last 20 years have dramatically increased the rate
of survival of these fragile newborns. However, as
GALE ENCYCLOPEDIA OF MEDICINE

Two factors are involved in the risk for CP associated with prematurity. First, premature babies are at
higher risk for various CP-associated medical complications, such as intracerebral hemorrhage, infection,
and difficulty in breathing, to name a few. Second, the
onset of premature labor may be induced, in part, by
complications that have already caused neurologic
damage in the fetus. A combination of both factors
almost certainly plays a role in some cases of CP. The
tendency toward premature delivery runs in families,
but the genetic mechanisms are far from clear.
An increase in multiple pregnancies in recent years,
especially in the United States, is blamed on the
increased use of fertility drugs. As the number of fetuses
in a pregnancy increases, the risks for abnormal development and premature delivery also increase. Children
from twin pregnancies have four times the risk of
developing CP as children from singleton pregnancies,
owing to the fact that more twin pregnancies are delivered prematurely. The risk for CP in a child of triplets
is up to 18 times greater. Furthermore, recent evidence
suggests that a baby from a pregnancy in which its
twin died before birth is at increased risk for CP.
Approximately 500,000 children and adults in the
United States have CP, and it is newly diagnosed
in about 6,000 infants and young children each year.
The incidence of CP has not changed much in the last
20–30 years. Ironically, while advances in medicine
have decreased the incidence from some causes—Rh
disease for example—they have increased it from
others, notably, prematurity and multiple pregnancies. No particular ethnic groups seem to be at higher
risk for CP. However, people of disadvantaged background are at higher risk due to poorer access to
proper prenatal care and advanced medical services.

Causes and symptoms
As noted, CP has many causes, making a discussion of the genetics of CP complicated. A number of
hereditary/genetic syndromes have signs and symptoms similar to CP, but usually also have problems
not typical of CP. Put another way, some hereditary
conditions ‘‘mimic’’ CP. Isolated CP, meaning CP that
GALE ENCYCLOPEDIA OF MEDICINE

is not a part of some other syndrome or disorder, is
usually not inherited.
It might be possible to group the causes of CP into
those that are genetic and those that are non-genetic,
but most would fall somewhere in between. Grouping
causes into those that occur during pregnancy
(prenatal), those that happen around the time of
birth (perinatal), and those that occur after birth
(postnatal), is preferable. CP related to premature
birth and multiple pregnancies (twins, triplets, etc.,
not ‘‘many pregnancies’’) is somewhat different and
considered separately.
Prenatal causes
Although much has been learned about human
embryology in the last few decades, a great deal
remains unknown. Studying prenatal human development is difficult because the embryo and fetus develop in a closed environment—the mother’s womb.
However, the relatively recent development of a number of prenatal tests has opened a window on the
process. Add to that more accurate and complete
evaluations of newborns, especially those with problems, and a clearer picture of what can go wrong
before birth is possible.
The complicated process of brain development
before birth is susceptible to many chance errors that
can result in abnormalities of varying degrees. Some of
these errors will result in structural anomalies of the
brain, while others may cause undetectable, but significant, abnormalities in how the cerebral cortex is
‘‘wired.’’ An abnormality in structure or wiring is
sometimes hereditary, but is most often due to chance,
or a cause unknown at this time. Whether and how
much genetics played a role in a particular brain
abnormality depends to some degree on the type of
anomaly and the form of CP it causes.
Several maternal-fetal infections are known to
increase the risk for CP, including rubella (German
measles, now rare in the United States), cytomegalovirus (CMV), and toxoplasmosis. Each of these infections is considered a risk to the fetus only if the mother
contracts it for the first time during that pregnancy.
Even in those cases, though, most babies will be born
normal. Most women are immune to all three infections by the time they reach childbearing age, but a
woman’s immune status can be determined using the
so-called TORCH (for Toxoplasmosis, Rubella,
Cytomegalovirus, and Herpes) test before or during
pregnancy.
Reserchers continue to study the role of perinatal
infection in development of cerebral palsy. New
779

Cerebral palsy

gestational age at delivery and birth weight of a baby
decrease, the risk for CP dramatically increases.
A term pregnancy is delivered at 37–41 weeks gestation.
The risk for CP in a preterm infant (32–37 weeks) is
increased about five-fold over the risk for an infant
born at term. Survivors of extremely preterm births
(less than 28 weeks) face as much as a 50-fold increase
in risk. About 50% of all cases of CP now being diagnosed are in children who were born prematurely.

Cerebral palsy

evidence in 2004 linked inflammatory cytokines to
possible cerebral injury that could lead to CP.
Scientists suggested new research with intravenous
immunoglobulin to limit inflammatory damage.
Just as a stroke can cause neurologic damage in an
adult, so too can this type of event occur in the fetus.
A burst blood vessel in the brain followed by uncontrolled bleeding (coagulopathy), known as intracerebral hemorrhage, could cause a fetal stroke, or a
cerebral blood vessel could be obstructed by a clot
(embolism). Infants who later develop CP, along with
their mothers, are more likely than other motherinfant pairs to test positive for factors that put them
at increased risk for bleeding episodes or blood clots.
Some coagulation disorders are strictly hereditary, but
most have a more complicated basis.
A teratogen is any substance to which a woman
is exposed that has the potential to harm the embryo
or fetus. Links between a drug or other chemical
exposure during pregnancy and a risk for CP are
difficult to prove. However, any substance that
might affect fetal brain development, directly or indirectly, could increase the risk for CP. Furthermore, any
substance that increases the risk for premature delivery and low birth weight, such as alcohol, tobacco, or
cocaine, among others, might indirectly increase the
risk for CP.
The fetus receives all nutrients and oxygen from
blood that circulates through the placenta. Therefore,
anything that interferes with normal placental function
might adversely affect development of the fetus, including the brain, or might increase the risk for premature
delivery. Structural abnormalities of the placenta, premature detachment of the placenta from the uterine
wall (abruption), and placental infections (chorioamnionitis) are thought to pose some risk for CP.
Certain conditions in the mother during pregnancy might pose a risk to fetal development leading
to CP. Women with autoimmune anti-thyroid or
anti-phospholipid (APA) antibodies are at slightly
increased risk for CP in their children. A potentially
important clue uncovered recently points toward high
levels of cytokines in the maternal and fetal circulation
as a possible risk for CP. Cytokines are proteins associated with inflammation, such as from infection or
autoimmune disorders, and they may be toxic to neurons in the fetal brain. More research is needed to
determine the exact relationship, if any, between high
levels of cytokines in pregnancy and CP. A woman has
some risk of developing the same complications in
more than one pregnancy, slightly increasing the risk
for more than one child with CP.
780

Serious physical trauma to the mother during
pregnancy could result in direct trauma to the fetus
as well, or injuries to the mother could compromise the
availability of nutrients and oxygen to the developing
fetal brain.
Perinatal causes
Birth asphyxia significant enough to result in CP
is now uncommon in developed countries. Tight
nuchal cord (umbilical cord around the baby’s neck)
and prolapsed cord (cord delivered before the baby)
are possible causes of birth asphyxia, as are bleeding
and other complications associated with placental
abruption and placenta previa (placenta lying over the
cervix).
Infection in the mother is sometimes not passed to
the fetus through the placenta, but is transmitted to
the baby during delivery. Any such infection that
results in serious illness in the newborn has the potential to produce some neurological damage.
Postnatal causes
The remaining 15% of CP is due to neurologic
injury sustained after birth. CP that has a postnatal
cause is sometimes referred to as acquired CP, but this
is only accurate for those cases caused by infection or
trauma.
Incompatibility between the Rh blood types of
mother and child (mother Rh negative, baby Rh positive) can result in severe anemia in the baby (erythroblastosis fetalis). This may lead to other complications,
including severe jaundice, which can cause CP. Rh
disease in the newborn is now rare in developed countries due to routine screening of maternal blood type
and treatment of pregnancies at risk. The routine,
effective treatment of jaundice due to other causes
has also made it an infrequent cause of CP in developed countries. Rh blood type poses a risk for recurrence of Rh disease if treatment is not provided.
Serious infections that affect the brain directly,
such as meningitis and encephalitis, may cause irreversible damage to the brain, leading to CP. A seizure
disorder early in life may cause CP, or may be the
product of a hidden problem that causes CP in addition to seizures. Unexplained (idiopathic) seizures
are hereditary in only a small percentage of cases.
Although rare in infants born healthy at or near
term, intracerebral hemorrhage and brain embolism,
like fetal stroke, are sometimes genetic.
Physical trauma to an infant or child resulting in
brain injury, such as from abuse, accidents, or near
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mental retardation/learning disabilities



behavioral disorders



seizure disorders



visual impairment

By definition, the defect in cerebral function causing CP is nonprogressive. However, the symptoms
of CP often change over time. Most of the symptoms
of CP relate in some way to the abnormal control of
muscles. To review, CP is categorized first by the type
of movement/postural disturbance(s) present, then by
a description of which limbs are affected, and finally
by the severity of motor impairment. For example,
spastic diplegia refers to continuously tight muscles
that have no voluntary control in both legs, while
athetoid quadraparesis describes uncontrolled writhing movements and muscle weakness in all four
limbs. These three-part descriptions are helpful in
providing a general picture, but cannot give a complete description of any one person with CP. In addition, the various ‘‘forms’’ of CP do not occur with
equal frequency—spastic diplegia is seen in more individuals than is athetoid quadraparesis. CP can also be
loosely categorized as mild, moderate, or severe, but
these are very subjective terms with no firm boundaries between them.



hearing loss



speech impairment (dysarthria)



abnormal sensation and perception

A muscle that is tensed and contracted is hypertonic, while excessively loose muscles are hypotonic.
Spastic, hypertonic muscles can cause serious orthopedic problems, including scoliosis (spine curvature),
hip dislocation, or contractures. A contracture
is shortening of a muscle, aided sometimes by a
weak-opposing force from a neighboring muscle.
Contractures may become permanent, or ‘‘fixed,’’
without some sort of intervention. Fixed contractures
may cause postural abnormalities in the affected
limbs. Clenched fists and contracted feet (equinus or
equinovarus) are common in people with CP.
Spasticity in the thighs causes them to turn in and
cross at the knees, resulting in an unusual method of
walking known as a ‘‘scissors gait.’’ Any of the joints
in the limbs may be stiff (immobilized) due to spasticity of the attached muscles.
Athetosis and dyskinesia often occur with spasticity, but do not often occur alone. The same is true of
ataxia. It is important to remember that ‘‘mild CP’’ or
‘‘severe CP’’ refers not only to the number of symptoms present, but also to the level of involvement of
any particular class of symptoms.
Mechanisms that can cause CP are not always
restricted to motor-control areas of the brain. Other
neurologically based symptoms may include:
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Cerebral palsy

drowning/suffocation, might cause CP. Likewise, ingestion of a toxic substance such as lead, mercury, poisons,
or certain chemicals could cause neurological damage.
Accidental overdose of certain medications might also
cause similar damage to the central nervous system.

These problems may have a greater impact on a
child’s life than the physical impairments of CP,
although not all children with CP are affected by
other problems. Many infants and children with CP
have growth impairment. About one-third of individuals with CP have moderate-to-severe mental retardation, one-third have mild mental retardation, and
one-third have normal intelligence.

Diagnosis
The signs of CP are not usually noticeable at birth.
Children normally progress through a predictable set
of developmental milestones through the first 18
months of life. Children with CP, however, tend to
develop these skills more slowly because of their motor
impairments, and delays in reaching milestones are
usually the first symptoms of CP. Babies with more
severe cases of CP are usually diagnosed earlier than
others.
Selected developmental milestones, and the ages
for normally acquiring them, are given below. If a
child does not acquire the skill by the age shown in
parentheses, there is some cause for concern.


sits well unsupported—6 months (8–10 months)



babbles—six months (eight months)



crawls—nine months (12 months)



finger feeds, holds bottle—nine months (12 months)



walks alone—12 months (15–18 months)



uses one or two words other than dada/mama—
12 months (15 months)



walks up and down steps—24 months (24–36
months)



turns pages in books; removes shoes and socks—24
months (30 months)

Children do not consistently favor one hand over
the other before 12–18 months, and doing so may be a
sign that the child has difficulty using the other hand.
This same preference for one side of the body may
show up as asymmetric crawling or, later on, favoring
one leg while climbing stairs.
781

Cerebral palsy

It must be remembered that children normally
progress at somewhat different rates, and slow beginning accomplishment is often followed by normal
development. Other causes for developmental delay—
some benign, some serious—should be excluded
before considering CP as the answer. CP is nonprogressive, so continued loss of previously acquired milestones indicates that CP is not the cause of the
problem.
No one test is diagnostic for CP, but certain factors increase suspicion. The Apgar score measures a
baby’s condition immediately after birth. Babies that
have low Apgar scores are at increased risk for CP.
Presence of abnormal muscle tone or movements may
indicate CP, as may the persistence of infantile
reflexes. Imaging of the brain using ultrasound,
x rays, MRI, and/or CT scans may reveal a structural
anomaly. Some brain lesions associated with CP
include scarring, cysts, expansion of the cerebral ventricles (hydrocephalus), periventricular leukomalacia
(an abnormality of the area surrounding the ventricles), areas of dead tissue (necrosis), and evidence of
an intracerebral hemorrhage or blood clot. Blood and
urine biochemical tests, as well as genetic tests, may be
used to rule out other possible causes, including muscle and peripheral nerve diseases, mitochondrial and
metabolic diseases, and other inherited disorders.
Evaluations by a pediatric developmental specialist
and a geneticist may be of benefit.

Treatment
Cerebral palsy cannot be cured, but many of the
disabilities it causes can be managed through planning
and timely care. Treatment for a child with CP
depends on the severity, nature, and location of the
primary muscular symptoms, as well as any associated
problems that might be present. Optimal care of a
child with mild CP may involve regular interaction
with only a physical therapist and occupational therapist, whereas care for a more severely affected child
may include visits to multiple medical specialists
throughout life. With proper treatment and an effective plan, most people with CP can lead productive,
happy lives.
Therapy
Spasticity, muscle weakness, coordination, ataxia,
and scoliosis are all significant impairments that
affect the posture and mobility of a person with CP.
Physical and occupational therapists work with the
patient, and the family, to maximize the ability to
move affected limbs, develop normal motor patterns,
782

and maintain posture. ‘‘Assistive technology,’’ things
such as wheelchairs, walkers, shoe inserts, crutches,
and braces, are often required. A speech therapist,
and high-tech aids such as computer-controlled
communication devices, can make a tremendous
difference in the life of those who have speech
impairments. A new experimental physical therapy
treatment was tested on children in 2004 that often
is used on adults who have had strokes. Called
constraint-induced movement therapy, it consists of
placing the child’s stronger arm in a case for three
weeks and giving him or her 21 straight days to
retrain the weaker arm.
Medications
Before fixed contractures develop, muscle-relaxant drugs such as diazepam (Valium), dantrolene
(Dantrium), and baclofen (Lioresal) may be prescribed. Botulinum toxin (Botox), a newer and highly
effective treatment, is injected directly into the affected
muscles. Alcohol or phenol injections into the nerve
controlling the muscle are another option. Multiple
medications are available to control seizures, and
athetosis can be treated using medications such as
trihexyphenidyl HCl (Artane) and benztropine
(Cogentin).
Surgery
Fixed contractures are usually treated with either
serial casting or surgery. The most commonly used
surgical procedures are tenotomy, tendon transfer,
and dorsal rhizotomy. In tenotomy, tendons of the
affected muscle are cut and the limb is cast in a more
normal position while the tendon regrows. Alternatively,
tendon transfer involves cutting and reattaching a
tendon at a different point on the bone to enhance
the length and function of the muscle. A neurosurgeon
performing dorsal rhizotomy carefully cuts selected
nerve roots in the spinal cord to prevent them from
stimulating the spastic muscles. Neurosurgical techniques in the brain such as implanting tiny electrodes
directly into the cerebellum, or cutting a portion of the
hypothalamus, have very specific uses and have had
mixed results.
Education
Parents of a child newly diagnosed with CP are
not likely to have the necessary expertise to coordinate
the full range of care their child will need. Although
knowledgeable and caring medical professionals are
indispensable for developing a care plan, a potentially
more important source of information and advice is
GALE ENCYCLOPEDIA OF MEDICINE

Asphyxia—Lack of oxygen. In the case of cerebral
palsy, lack of oxygen to the brain.
Ataxia—A deficiency of muscular coordination,
especially when voluntary movements are
attempted, such as grasping or walking.
Athetosis—A condition marked by slow, writhing,
involuntary muscle movements.
Coagulopathy—A disorder in which blood is either
too slow or too quick to coagulate (clot).
Contracture—A tightening of muscles that prevents
normal movement of the associated limb or other
body part.
Cytokine—A protein associated with inflammation
that, at high levels, may be toxic to nerve cells in the
developing brain.
Diplegia—Paralysis affecting like parts on both
sides the body, such as both arms or both legs.
Dorsal rhizotomy—A surgical procedure that
cuts nerve roots to reduce spasticity in affected
muscles.
Dyskinesia—Impaired ability to make voluntary
movements.
Hemiplegia—Paralysis of one side of the body.
Hypotonia—Reduced or diminished muscle tone.
Quadriplegia—Paralysis of all four limbs.
Serial casting—A series of casts designed to gradually move a limb into a more functional position.
Spastic—A condition in which the muscles are
rigid, posture may be abnormal, and fine motor
control is impaired.
Spasticity—Increased mucle tone, or stiffness,
which leads to uncontrolled, awkward movements.
Static encephalopathy—A disease of the brain that
does not get better or worse.
Tenotomy—A surgical procedure that cuts the tendon of a contracted muscle to allow lengthening.

Cerebral palsy can affect every stage of maturation, from childhood through adolescence to adulthood. At each stage, those with CP, along with their
caregivers, must strive to achieve and maintain the
fullest range of experiences and education consistent
with their abilities. The advice and intervention of
various professionals remains crucial for many people
with CP. Although CP itself is not considered a terminal disorder, it can affect a person’s lifespan by
increasing the risk for certain medical problems.
People with mild cerebral palsy may have near-normal
lifespans, but the lifespan of those with more severe
forms may be shortened. However, more than 90% of
infants with CP survive into adulthood.
The cause of most cases of CP remains unknown,
but it has become clear in recent years that birth
difficulties are not to blame in most cases. Rather,
developmental problems before birth, usually
unknown and generally undiagnosable, are responsible for most cases. The rate of survival for preterm
infants has leveled off in recent years, and methods to
improve the long-term health of these at-risk babies
are now being sought. Current research is also focusing on the possible benefits of recognizing and treating
coagulopathies and inflammatory disorders in the prenatal and perinatal periods. The use of magnesium
sulfate in pregnant women with preeclampsia or threatened preterm delivery may reduce the risk of CP in
very preterm infants. Finally, the risk of CP can be
decreased through good maternal nutrition, avoidance
of drugs and alcohol during pregnancy, and prevention or prompt treatment of infections.
Resources
BOOKS

Peacock, Judith. Cerebral Palsy. Mankato, MN: Capstone
Press, 2000.
Pimm, Paul. Living With Cerebral Palsy. Austin, TX:
Raintree Steck-Vaughn Publishers, 2000.
Pincus, Dion. Everything You Need to Know About Cerebral
Palsy. New York: Rosen Publishing Group, Inc., 2000.
PERIODICALS

other parents who have dealt with the same set of
difficulties. Support groups for parents of children
with CP can be significant sources of both practical
advice and emotional support. Many cities have support groups that can be located through the United
Cerebral Palsy Association, and most large medical
centers have special multidisciplinary clinics for children with developmental disorders.
GALE ENCYCLOPEDIA OF MEDICINE

Chambers, Henry G. ‘‘Research in Cerebral Palsy.’’ The
Exceptional Parent 29 (July 1999): 50.
‘‘Experimental Treatment Yields New Hope for Children
Battling Cerebral Palsy.’’ Drug Week February 27,
2004: 82.
Mohan, P.V., et al. ‘‘Can Polyclonal Intravenous
Immunoglobulin Limit Cytokine Mediated Cerebral
Damage and Chronic Lung Disease in Preterm
Infants?’’ Archives of Disease in Childhood January
2004: pF5–pF9.
783

Cerebral palsy

Prognosis

KEY TERMS

Cerebrospinal fluid (CSF) analysis

Myers, Scott M., and Bruce K. Shapiro. ‘‘Origins and
Causes of Cerebral Palsy: Symptoms and Diagnosis.’’
The Exceptional Parent 29 (April 1999): 28.
ORGANIZATIONS

Epilepsy Foundation of America. 4351 Garden City Dr., Suite
406, Landover, MD 20785-2267. (301) 459-3700 or (800)
332-1000. <http://www.epilepsyfoundation.org>.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (888)
663-4637. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Easter Seal Society. 230 W. Monroe St., Suite 1800,
Chicago, IL 60606-4802. (312) 726-6200 or (800)
221-6827. <http://www.easter-seals.org>.
National Institute of Neurological Disorders and Stroke. 31
Center Drive, MSC 2540, Bldg. 31, Room 8806,
Bethesda, MD 20814. (301) 496-5751 or (800) 352-9424.
<http://www.ninds.nih.gov>.
National Society of Genetic Counselors. 233 Canterbury
Dr., Wallingford, PA 19086-6617. (610) 872-1192.
<http://www.nsgc.org/GeneticCounselingYou.asp>.
United Cerebral Palsy Association, Inc. (UCP). 1660 L St.
NW, Suite 700, Washington, DC 20036-5602. (202)
776-0406 or (800) 872-5827. <http://www.ucpa.org>.
OTHER

‘‘Cerebral Palsy: Hope Through Research.’’ National
Institute of Neurological Disorders and Stroke. <http://
www.ninds.nih.gov/health_and_medical/pubs/
cerebral_palsyhtr.htm>.
‘‘Cerebral Palsy Information Page.’’ National Institute of
Neurological Disorders and Stroke. <http://
www.ninds.nih.gov/health_and_medical/pubs/
cerebral_palsy.htm>.

Scott J. Polzin, MS
Teresa G. Odle

fluid (CSF)
I Cerebrospinal
analysis
Definition
Cerebrospinal fluid (CSF) analysis is a laboratory
test to examine a sample of the fluid surrounding the
brain and spinal cord. This fluid is a clear, watery liquid
that protects the central nervous system from injury
and cushions it from the surrounding bone structure.
It contains a variety of substances, particularly glucose
(sugar), protein, and white blood cells from the immune
system. The fluid is withdrawn through a needle in a
procedure called a lumbar puncture.
784

Purpose
The purpose of a CSF analysis is to diagnose
medical disorders that affect the central nervous system. Some of these conditions include:


viral and bacterial infections, such as meningitis,
West Nile virus, herpes virus, and encephalitis



tumors or cancers of the nervous system



syphilis, a sexually transmitted disease



bleeding (hemorrhaging) around the brain and spinal
cord



multiple sclerosis, a disease that affects the myelin
coating of the nerve fibers of the brain and spinal cord



Guillain-Barr syndrome, an inflammation of the
nerves.



Early-onset Alzheimer’s disease. The levels of two
substances known as amyloid beta (1–42) and phosphorylated tau in CSF appear to be useful diagnostic
markers for early-onset Alzheimer’s.

CSF analysis is also used in forensic investigations
to identify the presence of illicit drugs (e. g., heroin) or
poisons in the bodies of murder, accidental overdose,
or suicide victims.

Precautions
In some circumstances, a lumbar puncture to withdraw a small amount of CSF for analysis may lead to
serious complications. Lumbar puncture should be
performed only with extreme caution, and only if the
benefits are thought to outweigh the risks, in certain
conditions. For example, in people who have blood
clotting (coagulation) or bleeding disorders, lumbar
puncture can cause bleeding that can compress the
spinal cord. If there is a large brain tumor or other
mass, removal of CSF can cause the brain to droop
down within the skull cavity (herniate), compressing
the brain stem and other vital structures, and leading to
irreversible brain damage or death. These problems are
easily avoided by checking blood coagulation through
a blood test and by doing a computed tomography scan
(CT) or magnetic resonance imaging (MRI) scan before
attempting the lumbar puncture. In addition, a lumbar
puncture procedure should never be performed at the
site of a localized skin infection on the lower back
because the infection may be introduced into the CSF
and may spread to the brain or spinal cord.

Description
The procedure to remove cerebrospinal fluid is
called a lumbar puncture, or spinal tap, because the
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A lumbar puncture takes about 30 minutes.
Patients can undergo the test in a doctor’s office,
laboratory, or outpatient hospital setting. Sometimes
it requires an inpatient hospital stay. If the patient has
spinal arthritis, is extremely uncooperative, or obese,
it may be necessary to introduce the spinal needle
using x-ray guidance.
In order to get an accurate sample of cerebrospinal fluid, it is critical that a patient is in the proper
position. The spine must be curved to allow as much
space as possible between the lower vertebrae, or
bones of the back, for the doctor to insert a lumbar
puncture needle between the vertebrae and withdraw a
small amount of fluid. The most common position is
for the patient to lie on his or her side with the back at
the edge of the exam table, head and chin bent down,
knees drawn up to the chest, and arms clasped around
the knees. (Small infants and people who are obese
may need to curve their spines in a sitting position.)
People should talk to their doctor if they have any
questions about their position because it is important
to be comfortable and to remain still during the entire
procedure. In fact, the doctor will explain the procedure to the patient (or guardian) so that the patient
can agree in writing to have it done (informed consent). If the patient is anxious or uncooperative, a
short-acting sedative may be given.
During a lumbar puncture, the doctor drapes the
back with a sterile covering that has an opening over
the puncture site and cleans the skin surface with an
antiseptic solution. Patients receive a local anesthetic
to minimize any pain in the lower back.
The doctor inserts a hollow, thin needle in the
space between two vertebrae of the lower back and
slowly advances it toward the spine. A steady flow of
clear cerebrospinal fluid, normally the color of water,
will begin to fill the needle as soon as it enters the
spinal canal. The doctor measures the cerebrospinal
fluid pressure with a special instrument called a manometer and withdraws several vials of fluid for laboratory analysis. The amount of fluid collected depends
on the type and number of tests needed to diagnose a
particular medical disorder.
GALE ENCYCLOPEDIA OF MEDICINE

In some cases, the doctor must remove and reposition the needle. This occurs when there is not an even
flow of fluid, the needle hits bone or a blood vessel, or
the patient reports sharp, unusual pain.

Preparation
Patients can go about their normal activities before
a lumbar puncture. Experts recommend that patients
relax before the procedure to release any muscle tension, since the lumbar puncture needle must pass
through muscle tissue before it reaches the spinal
canal. A patient’s level of relaxation before and during
the procedure plays a critical role in the test’s success.

Aftercare
After the procedure, the doctor covers the site of
the puncture with a sterile bandage. Patients must avoid
sitting or standing and remain lying down for as long as
six hours after the lumbar puncture. They should also
drink plenty of fluid to help prevent lumbar puncture
headache, which is discussed in the next section.

Risks
For most people, the most common side effect
after the removal of CSF is a headache. This occurs
in 10–30% of adult patients and in up to 40% of
children. It is caused by a decreased CSF pressure
related to a small leak of CSF through the puncture
site. These headaches usually are a dull pain, although
some people report a throbbing sensation. A stiff neck
and nausea may accompany the headache. Lumbar
puncture headaches typically begin within two days
after the procedure and persist from a few days to
several weeks or months.
Since an upright position worsens the pain, patients
with a lumbar puncture headache can control the pain
by lying in a flat position and taking a prescription or
non-prescription pain relief medication, preferably one
containing caffeine. In rare cases, the puncture site leak
is ‘‘patched’’ using the patient’s own blood.
People should talk to their doctor about complications from a lumbar puncture. In most cases, this
test to analyze CSF is a safe and effective procedure.
Some patients experience pain, difficulty urinating,
infection, or leakage of cerebrospinal fluid from the
puncture site after the procedure.

Normal results
Normal CSF is clear and colorless. It may be
cloudy in infections; straw- or yellow-colored if there
785

Cerebrospinal fluid (CSF) analysis

area of the spinal column used to obtain the sample is
in the lumbar spine, or lower section of the back. In
rare instances, such as a spinal fluid blockage in the
middle of the back, a doctor may perform a spinal tap
in the neck. The lower lumbar spine (usually between
the vertebrae known as L4–5) is preferable because the
spinal cord stops near L2, and a needle introduced
below this level will miss the spinal cord and encounter
only nerve roots, which are easily pushed aside.

Cerebrospinal fluid (CSF) analysis

Vertebrae

Spinal cord

Cerebrospinal fluid

/

/
/
/

/
/
/
/
/
/
/

/
/

During a lumbar puncture, or spinal tap, a procedure in which cerebrospinal fluid is aspirated, the physician inserts a hollow,
thin needle in the space between two vertebrae of the lower back and slowly advances it toward the spine. The cerebrospinal
fluid pressure is then measured and the fluid is withdrawn for laboratory analysis. (Illustration by Electronic Illustrators Group.)

is excess protein, as may occur with cancer or inflammation; blood-tinged if there was recent bleeding; or
yellow to brown (xanthochromic) if caused by an older
instance of bleeding.

to the CSF. If this is the case, there should be more red
blood cells in the first tube collected than in the last.

A series of laboratory tests analyze the CSF for a
variety of substances to rule out possible medical disorders of the central nervous system. The following
are normal values for commonly tested substances:

Abnormal test result values in the pressure or any
of the substances found in the cerebrospinal fluid may
suggest a number of medical problems including
a tumor or spinal cord obstruction; hemorrhaging
or bleeding in the central nervous system; infection
from bacterial, viral, or fungal microorganisms; or an
inflammation of the nerves. It is important for patients
to review the results of a cerebrospinal fluid analysis
with their doctor and to discuss any treatment plans.



CSF pressure: 50–180 mm H2O



glucose: 40%–85 mg/dL



protein: 15–50 mg/dL



leukocytes (white blood cells) total less than 5 per mL



lymphocytes: 60–70%



monocytes: 30–50%



neutrophils: none

Normally, there are no red blood cells in the CSF
unless the needle passes though a blood vessel on route
786

Abnormal results

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Normal Laboratory Values.’’ Section 21, Chapter 296
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
GALE ENCYCLOPEDIA OF MEDICINE

Encephalitis—An inflammation or infection of the
brain and spinal cord caused by a virus or as a
complication of another infection.
Guillain-Barré syndrome—An inflammation involving nerves that affect the extremities. The inflammation may spread to the face, arms, and chest.
Forensic—Referring to legal procedures or courts of
law. Forensic medicine is the branch of medicine
that obtains, analyzes, and presents medical evidence in criminal cases.
Immune system—Protects the body against infection.
Manometer—A device used to measure fluid
pressure.
Meningitis—An infection or inflammation of the
membranes or tissues that cover the brain and
spinal cord, and caused by bacteria or a virus.
Multiple sclerosis—A disease that destroys the covering (myelin sheath) of nerve fibers of the brain and
spinal cord.
Spinal canal—The cavity or hollow space within
the spine that contains cerebrospinal fluid.
Vertebrae—The bones of the spinal column. There
are 33 along the spine, with five (called L1–L5)
making up the lower lumbar region.

PERIODICALS

Boivin, G. ‘‘Diagnosis of Herpesvirus Infections of the
Central Nervous System.’’ Herpes 11, Supplement 2
(June 2004): 48A–56A.
Roos, K. L. ‘‘West Nile Encephalitis and Myelitis.’’ Current
Opinion in Neurology 17 (June 2004): 343–346.
Schoonenboom, N. S., Y. A. Pijnenburg, C. Mulder, et al.
‘‘Amyloid Beta(1-42) and Phosphorylated Tau in CSF
as Markers for Early-Onset Alzheimer Disease.’’
Neurology 62 (May 11, 2004): 1580–1584.
Sharma, A. N., L. S. Nelson, and R. S. Hoffman.
‘‘Cerebrospinal Fluid Analysis in Fatal Thallium
Poisoning: Evidence for Delayed Distribution into the
Central Nervous System.’’ American Journal of Forensic
Medicine and Pathology 25 (June 2004): 156–158.
Wyman, J., and S. Bultman. ‘‘Postmortem Distribution of
Heroin Metabolites in Femoral Blood, Liver,
Cerebrospinal Fluid, and Vitreous Humor.’’ Journal of
Analytical Toxicology 28 (May-June 2004): 260–263.
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave.,
St. Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.
GALE ENCYCLOPEDIA OF MEDICINE

American College of Forensic Examiners International
(ACFEI). 2750 East Sunshine, Springfield, MO 65804.
(800) 423-9737 or (417) 881-3818. Fax: (417) 881-4702.
<http://www.acfei.com>.

Martha Floberg Robbins
Rebecca J. Frey, PhD

Cerebrovascular accident see Stroke
Cerebrovascular amyloidosis see Cerebral
amyloid angiopathy

I Cerumen impaction
Definition
Cerumen impaction is a condition in which earwax has become tightly packed in the external ear
canal to the point that the canal is blocked.

Description
Cerumen impaction develops when earwax accumulates in the inner part of the ear canal and blocks
the eardrum. It affects between 2%–6% of the general
population in the United States. Impaction does not
happen under normal circumstances because cerumen
is produced by glands in the outer part of the ear canal;
it is not produced in the inner part. The cerumen traps
sand or dust particles before they reach the ear drum.
It also protects the outer part of the ear canal because
it repels water. The slow movement of the outer layer
of skin of the ear canal carries cerumen toward the
outer opening of the ear. As the older cerumen reaches
the opening of the ear, it dries out and falls away.

Causes and symptoms
Causes
Cerumen is most likely to become impacted when
it is pushed against the eardrum by cotton-tipped
applicators, hair pins, or other objects that people
put in their ears; and when it is trapped against the
eardrum by a hearing aid. Less common causes of
cerumen impaction include overproduction of earwax
by the glands in the ear canal, or an abnormally
shaped ear canal.
Symptoms
The most important symptom of cerumen impaction is partial loss of hearing. Other symptoms are
787

Cerumen impaction

KEY TERMS

Cerumen impaction

Syringe

Eardrum
Wax
Stream of fluid

Ear wax is removed by flushing the ear canal with warm fluid. (Illustration by Argosy, Inc.)

itching, tinnitus (noise or ringing in the ears), a sensation of fullness in the ear, and pain.

Diagnosis
The diagnosis of impacted cerumen is usually
made by examining the ear canal and eardrum with
an otoscope, an instrument with a light attached that
allows the doctor to look into the canal.

throat (ENT) specialist. The specialist can remove the
wax with a vacuum device or a curette, which is a small
scoop-shaped surgical instrument.
Some doctors prescribe special ear drops, such as
Cerumenex, to soften the wax. The most common side
effect of Cerumenex is an allergic skin reaction. Overthe-counter wax removal products include Debrox or
Murine Ear Drops. A 3% solution of hydrogen peroxide may also be used. These products are less likely
to irritate the skin of the ear.

Treatment
Irrigation is the most common method of removing impacted cerumen. It involves washing out the ear
canal with water from a commercial irrigator or a
syringe with a catheter attached. Although some doctors use Water Piks to remove cerumen, most do not
recommend them because the stream of water is too
forceful and may damage the eardrum. The doctor
may add a small amount of alcohol, hydrogen peroxide, or other antiseptic. The water must be close to
body temperature; if it is too cold or too warm, the
patient may feel dizzy or nauseated. After the ear has
been irrigated, the doctor will apply antibiotic ear
drops to protect the ear from infection.
Irrigation should not be used to remove cerumen
if the patient’s eardrum is ruptured or missing; if the
patient has a history of chronic otitis media (inflammation of the middle ear) or a myringotomy (cutting
the eardrum to allow fluid to escape from the middle
ear); or if the patient has hearing in only one ear.
If irrigation cannot be used or fails to remove the
cerumen, the patient is referred to an ear, nose, and
788

Alternative treatment
One alternative method that is sometimes touted
as a way to remove impacted cerumen is ear candling.
Ear candling involves the insertion of a burning candle
or a cone of wax-soaked linen or cotton into the
affected ear. The person lies on his or her side with
the affected ear uppermost. A collecting plate is placed
on the ear to catch melted wax. The cone or candle is
threaded through a hole in the plate into the ear canal
and lit. A variation on this technique involves blowing
herbal smoke into the ear through homemade pottery
cones. Practitioners of ear candling claim that the heat
from the burning candle or smoke creates a vacuum
that draws out the impacted cerumen. Some also claim
that ear candling improves hearing, relieves sinus infections, cures earache or swimmer’s ear, stops tinnitus, or
purifies the mind. None of these claims are true. Ear
candling is not recognized as an acceptable alternative
practice by naturopaths, homeopaths, practitioners of
Native American medicine, or any other authority on
complementary and alternative medicine.
GALE ENCYCLOPEDIA OF MEDICINE

of perforating the ear drum or damaging the fragile
skin covering the ear canal, causing bleeding and the
risk of infection.

Cerumen—The medical term for earwax.
Curette—A small scoop-shaped surgical instrument that can be used to remove cerumen if irrigation does not work or cannot be used.
Ear candling—An alternative method for removing
impacted cerumen with a lighted hollow cone of
paraffin or beeswax. It does not work, and is not
considered an acceptable treatment for any ear
problem or disorder.
Impaction—A condition in which earwax has
become tightly packed in the outer ear to the
point that the external ear canal is blocked.
Irrigation—The technique of removing cerumen
from the ear canal by flushing it with water.
Myringotomy—Surgical cutting of the ear drum to
allow fluid to escape from the middle ear.
Otitis media—Inflammation of the middle ear.
Patients who have had recurrent otitis media
should not have cerumen removed by irrigation.
Tinnitus—A sensation of noise or ringing in the
ears. Tinnitus may be a symptom of cerumen
impaction.

Ear candling is not only an ineffective way to
remove impacted cerumen, it can actually damage
the ear. According to a 1996 survey of 122 otolaryngologists (doctors who specialize in treating ear, nose,
and throat disorders) in the Spokane area, the doctors
reported 21 severe ear injuries resulting from ear candling, including 13 cases of external burns, 7 cases of ear
canal obstruction from melted candle wax, and 1 case
of eardrum perforation. Ear candles cannot legally be
sold as health devices in the United States because they
do not have Food and Drug Administration (FDA)
approval. A similar ban is in effect in Canada. Ear
candles are, however, available over the Internet and
in some health food stores with the labeling ‘‘for
entertainment only.’’

Prognosis
In most cases, impacted cerumen is successfully
removed by irrigation with no lasting side effects.
Irrigation can, however, lead to infection of the outer
or the middle ear if the patient has a damaged or
absent ear drum. Patients who try to remove earwax
themselves with hair pins or similar objects run the risk
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
The best method of cleaning the external ear is to
wipe the outer opening with a damp washcloth folded
over the index finger, without going into the ear canal
itself. Two techniques have been recommended to
prevent cerumen from reaccumulating in the ear. The
patient may place two or three drops of mineral oil
into each ear once a week, allow it to remain for two or
three minutes, and rinse it out with warm water; or
place two drops of Domeboro otic solution in each ear
once a week after showering.
Patients who wear hearing aids should have their
ears examined periodically for signs of cerumen
accumulation.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘External Ear: Obstructions.’’ Section 7, Chapter 83 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Jackler, Robert K., MD, and Michael J. Kaplan, MD.
‘‘Cerumen Impaction.’’ In ‘‘Ear, Nose, & Throat.’’
Current Medical Diagnosis & Treatment 2001, edited
by L. M. Tierney, Jr., MD, et al., 40th ed. New York:
Lange Medical Books/McGraw-Hill, 2001.
PERIODICALS

Crummer, R. W., and G. A. Hassan. ‘‘Diagnostic Approach
to Tinnitus.’’ American Family Physician 69 (January 1,
2004): 120–126.
Ernst, E. ‘‘Ear Candles—A Triumph of Ignorance Over
Science.’’ Journal of Laryngology and Otology 118
(January 2004): 1–2.
Whatley, V. N., C. L. Dodds, and R. I. Paul.
‘‘Randomized Clinical Trial of Docusate,
Triethanolamine Polypeptide, and Irrigation in
Cerumen Removal in Children.’’ Archives of
Pediatrics and Adolescent Medicine 157 (December
2003): 1177–1180.
ORGANIZATIONS

American Academy of Family Physicians (AAFP). 11400
Tomahawk Creek Parkway, Leawood, KS 66211-2672.
(800) 274-2237 or (913) 906-6000. <http://
www.aafp.org>.
American Academy of Otolaryngology, Head and Neck
Surgery, Inc.. One Prince St., Alexandria, VA 223143357. (703) 836-4444. <http://www.entnet.org>.
789

Cerumen impaction

KEY TERMS

Cervical cancer

OTHER

Health Canada/Santé Canada. It’s Your Health: Ear
Candling. Ottawa: Health Canada/Santé Canada, 2002.

Rebecca J. Frey, PhD

Cervical biopsy see Cervical conization

I Cervical cancer
Definition
Cervical cancer is a disease in which the cells of the
cervix become abnormal and start to grow uncontrollably, forming tumors.

Description
In the United States, cervical cancer is the fifth
most common cancer among women aged 35–54, and
the third most common cancer of the female reproductive tract. In some developing countries, it is the
most common type of cancer. It generally begins as an
abnormality in the cells on the outside of the cervix.
The cervix is the lower part or neck of the uterus
(womb). It connects the body of the uterus to the
vagina (birth canal).
Approximately 90% of cervical cancers are squamous cell carcinomas. This type of cancer originates in
the thin, flat, squamous cells on the surface of the
ectocervix, the part of the cervix that is next to the
vagina. (Squamous cells are the thin, flat cells of
the surfaces of the skin and cervix and linings of
various organs.) Another 10% of cervical cancers are
of the adenocarcinoma type. This cancer originates in
the mucus-producing cells of the inner or endocervix,
near the body of the uterus. Occasionally, the cancer
may have characteristics of both types and is called
adenosquamous carcinoma or mixed carcinoma.
The initial changes that may occur in some cervical
cells are not cancerous. However, these precancerous
cells form a lesion called dysplasia or a squamous
intraepithelial lesion (SIL), since it occurs within the
epithelial or outer layer of cells. These abnormal cells
can also be described as cervical intraepithelial neoplasia (CIN). Moderate to severe dysplasia may be called
carcinoma in situ or non-invasive cervical cancer.
Dysplasia is a common condition and the abnormal cells often disappear without treatment. However,
these precancerous cells can become cancerous. This
may take years, although it can happen in less than a
790

year. Eventually, the abnormal cells start to grow
uncontrollably into the deeper layers of the cervix,
becoming an invasive cervical cancer.
Although cervical cancer used to be one of the
most common causes of cancer death among
American women, in the past 40 years there has been
a 75% decrease in mortality. This is primarily due to
routine screening with Pap tests (Pap smear), to identify precancerous and early-invasive stages of cervical
cancer. With treatment, these conditions have a cure
rate of nearly 100%.
Worldwide, there are more than 400,000 new
cases of cervical cancer diagnosed each year. The
American Cancer Society (ACS) estimated 13,000
new cases of invasive cervical cancer diagnosed in the
United States in 2002. More than one million women
were diagnosed with a precancerous lesion or noninvasive cancer of the cervix in 2001.
Older women are at the highest risk for cervical
cancer. Although girls under the age of 15 rarely
develop this cancer, the risk factor begins to increase
in the late teens. Rates for carcinoma in situ peak
between the ages of 20 and 30. In the United States,
the incidence of invasive cervical cancer increases
rapidly with age for African-American women over
the age of 25. The incidence rises more slowly for
Caucasian women. However, women over age 65
account for more than 25% of all cases of invasive
cervical cancer.
The incidence of cervical cancer is highest among
poor women and among women in developing
countries. In the United States, the death rates from
cervical cancer are higher among Hispanic, Native
American, and African-American women than
among Caucasian women. These groups of women
are much less likely to receive regular Pap tests.
Therefore, their cervical cancers usually are diagnosed
at a much later stage, after the cancer has spread to
other parts of the body.

Causes and symptoms
Human papillomavirus
Infection with the common human papillomavirus
(HPV) is a cause of approximately 90% of all cervical
cancers. There are more than 80 types of HPV. About
30 of these types can be transmitted sexually, including
those that cause genital warts (papillomas). About half
of the sexually transmitted HPVs are associated with
cervical cancer. These ‘‘high-risk’’ HPVs produce a
protein that can cause cervical epithelial cells to grow
uncontrollably. The virus makes a second protein that
GALE ENCYCLOPEDIA OF MEDICINE

More than six million women in the United States
have persistent HPV infections, for which there are no
cure. Nevertheless, most women with HPV do not
develop cervical cancer.
Symptoms of invasive cervical cancer
Most women do not have symptoms of cervical
cancer until it has become invasive. At that point, the
symptoms may include:


unusual vaginal discharge



light vaginal bleeding or spots of blood outside of
normal menstruation



pain or vaginal bleeding with sexual intercourse



post-menopausal vaginal bleeding

Once the cancer has invaded the tissue surrounding the cervix, a woman may experience pain in the
pelvic region and heavy bleeding from the vagina.

Diagnosis
The Pap test
Most often, cervical cancer is first detected with a
Pap test that is performed as part of a regular pelvic
examination. The vagina is spread with a metal
or plastic instrument called a speculum. A swab is used
to remove mucus and cells from the cervix. This sample
is sent to a laboratory for microscopic examination.
The Pap test is a screening tool rather than a
diagnostic tool. It is very efficient at detecting cervical
abnormalities. The Bethesda System commonly is
used to report Pap test results. A negative test means
that no abnormalities are present in the cervical tissue.
A positive Pap test describes abnormal cervical cells as
low-grade or high-grade SIL, depending on the extent
of dysplasia. About 5–10% of Pap tests show at least
mild abnormalities. However, a number of factors
other than cervical cancer can cause abnormalities,
including inflammation from bacteria or yeast infections. A few months after the infection is treated, the
Pap test is repeated.
Biopsy
Following an abnormal Pap test, a colposcopy is
usually performed. The physician uses a magnifying
scope to view the surface of the cervix. The cervix may
be coated with an iodine solution that causes normal
cells to turn brown and abnormal cells to turn white or
GALE ENCYCLOPEDIA OF MEDICINE

yellow. This is called a Schiller test. If any abnormal
areas are observed, a colposcopic biopsy may be performed. A biopsy is the removal of a small piece of
tissue for microscopic examination by a pathologist.
Other types of cervical biopsies may be performed.
An endocervical curettage is a biopsy in which a narrow
instrument called a curette is used to scrape tissue from
inside the opening of the cervix. A cone biopsy, or
conization, is used to remove a cone-shaped piece of
tissue from the cervix. In a cold knife cone biopsy, a
surgical scalpel or laser is used to remove the tissue.
A loop electrosurgical excision procedure (LEEP) is a
cone biopsy using a wire that is heated by an electrical
current. Cone biopsies can be used to determine
whether abnormal cells have invaded below the surface
of the cervix. They also can be used to treat many
precancers and very early cancers. Biopsies may be
performed with a local or general anesthetic. They
may cause cramping and bleeding.
Diagnosing the stage
Following a diagnosis of cervical cancer, various
procedures may be used to stage the disease (determine
how far the cancer has spread). For example, additional pelvic exams may be performed under
anesthesia.
There are several procedures for determining if
cervical cancer has invaded the urinary tract. With
cystoscopy, a lighted tube with a lens is inserted
through the urethra (the urine tube from the bladder
to the exterior) and into the bladder to examine these
organs for cancerous cells. Tissue samples may be
removed for microscopic examination by a pathologist. Intravenous urography (intravenous pyelogram or
IVP) is an x ray of the urinary system, following the
injection of special dye. The kidneys remove the dye
from the bloodstream and the dye passes into the
ureters (the tubes from the kidneys to the bladder)
and bladder. IVP can detect a blocked ureter, caused
by the spread of cancer to the pelvic lymph nodes
(small glands that are part of the immune system).
A procedure called proctoscopy or sigmoidoscopy
is similar to cystoscopy. It is used to determine
whether the cancer has spread to the rectum or lower
large intestine.
Computed tomography (CT) scans, ultrasound, or
other imaging techniques may be used to determine
the spread of cancer to various parts of the body. With
a CT scan, an x-ray beam rotates around the body,
taking images from various angles. It is used to determine if the cancer has spread to the lymph nodes.
Magnetic resonance imaging (MRI), which uses a
791

Cervical cancer

interferes with tumor suppressors that are produced by
the human immune system. The HPV-16 strain is
thought to be a cause of about 50% of cervical cancers.

Cervical cancer

magnetic field to image the body, sometimes is used
for evaluating the spread of cervical cancer. Chest
x rays may be used to detect cervical cancer that has
spread to the lungs.

Treatment
Following a diagnosis of cervical cancer, the physician takes a medical history and performs a complete
physical examination. This includes an evaluation of
symptoms and risk factors for cervical cancer. The
lymph nodes are examined for evidence that the cancer
has spread from the cervix. The choice of treatment
depends on the clinical stage of the disease.



Stage IV: Cancer has spread to other parts of the
body



Stage IVA: Cancer has spread to the bladder or
rectum



Stage IVB: Cancer has spread to distant organs such
as the lungs



Recurrent: Following treatment, cancer has returned
to the cervix or some other part of the body

In addition to the stage of the cancer, factors such
as a woman’s age, general health, and preferences may
influence the choice of treatment. The exact location
of the cancer within the cervix and the type of cervical
cancer also are important considerations.

The FIGO system of staging
The International Federation of Gynecologists
and Obstetricians (FIGO) system usually is used to
stage cervical cancer:


Stage 0: Carcinoma in situ; non-invasive cancer that
is confined to the layer of cells lining the cervix



Stage I: Cancer that has spread into the connective
tissue of the cervix but is confined to the uterus

Treatment of precancer and carcinoma in situ
Most low-grade SILs that are detected with Pap
tests revert to normal without treatment. Most highgrade SILs require treatment. Treatments to remove
precancerous cells include:


cold knife cone biopsy



LEEP

Stage IA: Very small cancerous area that is visible
only with a microscope



cryosurgery (freezing the cells with a metal probe)



cauterization or diathermy (burning off the cells)



Stage IA1: Invasion area is less than 3 mm (0.13 in)
deep and 7 mm (0.33 in) wide



laser surgery (burning off the cells with a laser beam)



Stage IA2: Invasion area is 3–5 mm (0.13–0.2 in)
deep and less than 7 mm (0.33 in) wide



Stage IB: Cancer can be seen without a microscope
or is deeper than 5 mm (0.2 in) or wider than 7 mm
(0.33 in)



Stage IB1: Cancer is no larger than 4 cm (1.6 in)



Stage IB2: Stage IB cancer is larger than 4 cm (1.6 in)



Stage II: Cancer has spread from the cervix but is
confined to the pelvic region



Stage IIA: Cancer has spread to the upper region of
the vagina, but not to the lower one-third of the
vagina



Stage IIB: Cancer has spread to the parametrial tissue adjacent to the cervix



Stage III: Cancer has spread to the lower one-third of
the vagina or to the wall of the pelvis and may be
blocking the ureters



Stage IIIA: Cancer has spread to the lower vagina
but not to the pelvic wall



Stage IIIB: Cancer has spread to the pelvic wall and/
or is blocking the flow of urine through the ureters to
the bladder



792

These methods also may be used to treat cancer
that is confined to the surface of the cervix (stage 0)
and other early-stage cervical cancers in women who
may want to become pregnant. They may be used in
conjunction with other treatments. These procedures
may cause bleeding or cramping. All of these treatments require close follow-up to detect any recurrence
of the cancer.
Surgery
A simple hysterectomy is used to treat some stages
0 and IA cervical cancers. Usually only the uterus is
removed, although occasionally the fallopian tubes
and ovaries are removed as well. The tissues adjoining
the uterus, including the vagina, remain intact. The
uterus may be removed either through the abdomen or
the vagina.
In a radical hysterectomy, the uterus and adjoining tissues, including the ovaries, the upper region
(1 in) of the vagina near the cervix, and the pelvic
lymph nodes, are all removed. A radical hysterectomy usually involves abdominal surgery. However, it
can be performed vaginally, in combination with
a laparoscopic pelvic lymph node dissection. With
laparoscopy, a tube is inserted through a very small
GALE ENCYCLOPEDIA OF MEDICINE

recurrent cervical cancers usually are treated with a
combination of external and internal radiation and chemotherapy. The common drugs used for cervical cancer
are cisplatin, ifosfamide, and fluorouracil. These may
be injected or taken by mouth. The National Cancer
Institute recommends that chemotherapy with cisplatin
be considered for all women receiving radiation therapy
for cervical cancer.

If cervical cancer recurs following treatment, a
pelvic exenteration (extensive surgery) may be performed. This includes a radical hysterectomy, with the
additional removal of the bladder, rectum, part of the
colon, and/or all of the vagina. Such operations require
the creation of new openings for the urine and feces.
A new vagina may be created surgically. Often the
clitoris and other outer genitals are left intact.

The side effects of chemotherapy depend on a
number of factors, including the type of drug, the
dosage, and the length of the treatment. Side effects
may include:

Recovery from a pelvic exenteration may take six
months to two years. This treatment is successful with
40–50% of recurrent cervical cancers that are confined
to the pelvis. If the recurrent cancer has spread to
other organs, radiation or chemotherapy may be used
to alleviate some of the symptoms.
Radiation
Radiation therapy, which involves the use of highdosage x rays or other high-energy waves to kill cancer
cells, often is used for treating stages IB, IIA, and IIB
cervical cancers, or in combination with surgery. With
external-beam radiation therapy, the rays are focused
on the pelvic area from a source outside the body. With
implant or internal radiation therapy, a pellet of radioactive material is placed internally, near the tumor.
Alternatively, thin needles may be used to insert the
radioactive material directly into the tumor.
Radiation therapy to the pelvic region can have
many side effects:


skin reaction in the area of treatment



fatigue



upset stomach and loose bowels



vaginal stenosis (narrowing of the vagina due to
build-up of scar tissue) leading to painful sexual
intercourse



premature menopause in young women



problems with urination
Chemotherapy

Chemotherapy, the use of one or more drugs to kill
cancer cells, is used to treat disease that has spread
beyond the cervix. Most often it is used following surgery or radiation treatment. Stages IIB, III, IV, and
GALE ENCYCLOPEDIA OF MEDICINE



nausea and vomiting



fatigue



changes in appetite



hair loss



mouth or vaginal sores



infections



menstrual cycle changes



premature menopause



infertility



bleeding or anemia (low red blood cell count)

With the exception of menopause and infertility,
most of the side effects are temporary.

Alternative treatment
Biological therapy sometimes is used to treat cervical cancer, either alone or in combination with
chemotherapy. Treatment with the immune-system
protein interferon is used to boost the immune
response. Biological therapy can cause temporary
flu-like symptoms and other side effects.
Some research suggests that vitamin A (carotene)
may help to prevent or stop cancerous changes in cells
such as those on the surface of the cervix. Other studies
suggest that vitamins C and E may reduce the risk of
cervical cancer.

Prognosis
For cervical cancers that are diagnosed in the preinvasive stage, the five-year-survival rate is almost
100%. When cervical cancer is detected in the early
invasive stages, approximately 91% of women survive
five years or more. Stage IVB cervical cancer is not
considered to be curable. The five-year-survival rate
for all cervical cancers combined is about 70%. The
death rate from cervical cancer continues to decline by
about 2% each year. Women over age 65 account for
793

Cervical cancer

surgical incision for the removal of the lymph nodes.
These operations are used to treat stages IA2, IB, and
IIA cervical cancers, particularly in young women.
Following a hysterectomy, the tissue is examined to
see if the cancer has spread and requires additional
radiation treatment. Women who have had hysterectomies cannot become pregnant, but complications
from a hysterectomy are rare.

Cervical cancer

40–50% of all deaths from cervical cancer. About 4,100
women died of the disease in the United States in 2002.

Prevention
Viral infections
Most cervical cancers are preventable. More than
90% of women with cervical cancer are infected with
HPV. HPV infection is the single most important risk
factor. This is particularly true for young women
because the cells lining the cervix do not fully mature
until age 18. These immature cells are more susceptible
to cancer-causing agents and viruses.
Since HPV is a sexually-transmitted infection,
sexual behaviors can put women at risk for HPV
infection and cervical cancer. These behaviors include:


sexual intercourse at age 16 or younger



partners who began having intercourse at a young age



multiple sexual partners



sexual partners who have had multiple partners
(‘‘high-risk males’’)



a partner who has had a previous sexual partner with
cervical cancer

HPV infection may not produce any symptoms,
so sexual partners may not know that they are
infected. In 2003, a new DNA screening test was
approved by the FDA to test for HPV at the same
time as the Pap test. Condoms do not necessarily prevent HPV infection. However, in 2003, a preliminary
study demonstrated that a vaccine against the type of
HPV that causes the most cervical cancers showed
promise in preventing HPV infection. Scientists predict having FDA approval of an HPV vaccine by
about 2008 or 2010.
Infection with the human immunodeficiency virus
(HIV) that causes acquired immunodeficiency syndrome (AIDS) is a risk factor for cervical cancer.
Women who test positive for HIV may have impaired
immune systems that cannot correct precancerous conditions. Furthermore, sexual behavior that puts women
at risk for HIV infection, also puts them at risk for HPV
infection. There is some evidence suggesting that
another sexually transmitted virus, the genital herpes
virus, also may be involved in cervical cancer.

cervical cells. The risk increases with the number of
years a woman smokes and the amount she smokes.
A 2003 study also linked smoking to poorer outcomes
and survivals in cervical cancer patients.
Diet and drugs
Diets that are low in fruits and vegetables increase
the risk of cervical cancer. A 2003 study also linked
obesity to increased risk for cervical adenocarcinoma.
Even women who were overweight had a higher incidence of the disease. The link appears to be increase
levels of estrogen. Excessive fat tissue influences levels
of estrogen and other sex hormones. Women also have
an increased risk of cervical cancer if their mothers
took the drug diethylstilbestrol (DES) while they were
pregnant. This drug was given to women between 1940
and 1971 to prevent miscarriages. Some statistical
studies have suggested that the long-term use of oral
contraceptives may slightly increase the risk of cervical
cancer.
Pap tests
Most cases of cervical cancers are preventable,
since they start with easily detectable precancerous
changes. Therefore, the best prevention for cervical
cancer is a regular Pap test. The ACS revised its guidelines for regular screening in late 2002. In brief, women
should begin having Pap tests about three years after
having sexual intercourse, but no later than 21 years of
age. Women should continue screening every year
with regular Pap tests until age 30. Once a woman
has had three normal results in a row, she may get
screened every two to three years. A doctor may suggest more frequent screening if a woman has certain
risk factors for cervical cancer. Women who have had
total hysterectomies including the removal of the cervix and those over age 70 who have had three normal
results generally do not need to continue having Pap
tests under the new guidelines.
The National Breast and Cervical Cancer Early
Detection Program provides free or low-cost Pap tests
and treatment for women without health insurance,
for older women, and for members of racial and ethnic
minorities. The program is administered through individual states, under the direction of the Centers for
Disease Control and Prevention.

Smoking
Smoking may double the risk of cervical cancer. In
fact, studies suggest that nearly 50% of women diagnosed with cervical cancer smoke. Chemicals produced by tobacco smoke can damage the DNA of
794

Special concerns
If a woman is diagnosed with very early-stage (IA)
cervical cancer while pregnant, the physician usually
will recommend a hysterectomy after the baby is born.
GALE ENCYCLOPEDIA OF MEDICINE

Adenocarcinoma—Cervical cancer that originates in
the mucus-producing cells of the inner or endocervix.
Biopsy—Removal of a small sample of tissue for
examination under a microscope; used for the diagnosis and treatment of cervical cancer and precancerous conditions.
Carcinoma in situ—Cancer that is confined to the cells
in which it originated and has not spread to other tissues.
Cervical intraepithelial neoplasia (CIN)—Abnormal
cell growth on the surface of the cervix.
Cervix—Narrow, lower end of the uterus forming the
opening to the vagina.
Colposcopy—Diagnostic procedure using a hollow,
lighted tube (colposcope) to look inside the cervix
and uterus.
Conization—Cone biopsy; removal of a cone-shaped
section of tissue from the cervix for diagnosis or
treatment.
Dysplasia—Abnormal cellular changes that may
become cancerous.
Endocervical curettage—Biopsy performed with a
curette to scrape the mucous membrane of the cervical canal.
Human papillomavirus (HPV)—Virus that causes
abnormal cell growth (warts or papillomas); some
types can cause cervical cancer.

For later-stage cancers, the pregnancy is terminated or
the baby is removed by cesarean section as soon as it
can survive outside the womb. This is followed by a
hysterectomy and/or radiation treatment. For the
most advanced stages of cervical cancer, treatment is
initiated despite the pregnancy.
Many women with cervical cancer have hysterectomies, which are major surgeries. Although normal
activities, including sexual intercourse, can be resumed
in four to eight weeks, a woman may have emotional
problems following a hysterectomy. A strong support
system can help with these difficulties.
Resources
BOOKS

Holland, Jimmie C., and Sheldon Lewis. The Human Side of
Cancer: Living with Hope, Coping with Uncertainty.
New York: HarperCollins, 2000.
Runowicz, Carolyn D., Jeanne A. Petrek, and Ted
S. Gansler. Women and Cancer: A Thorough and
GALE ENCYCLOPEDIA OF MEDICINE

Hysterectomy—Removal of the uterus.
Interferon—Potent immune-defense protein produced by viral-infected cells; used as an anti-cancer
and anti-viral drug.
Laparoscopy—Laparoscopic pelvic lymph node dissection; insertion of a tube through a very small
surgical incision to remove lymph nodes.
Loop electrosurgical excision procedure (LEEP)—
Cone biopsy performed with a wire that is heated
by electrical current.
Lymph nodes—Small round glands, located throughout the body, that filter the lymphatic fluid; part of the
body’s immune defense.
Pap test—Pap smear; removal of cervical cells to
screen for cancer.
Pelvic exenteration—Extensive surgery to remove
the uterus, ovaries, pelvic lymph nodes, part or all
of the vagina, and the bladder, rectum, and/or part of
the colon.
Squamous cells—Thin, flat cells on the surfaces of
the skin and cervix and linings of various organs.
Squamous intraepithelial lesion (SIL)—Abnormal
growth of squamous cells on the surface of the
cervix.
Vaginal stenosis—Narrowing of the vagina due to a
build-up of scar tissue.

Compassionate Resource for Patients and their Families.
New York: Villard Books, 1999.
PERIODICALS

‘‘American Cancer Society Issues New Early Detection
Guidelines.’’ Women’s Health Weekly December 19,
2002: 12.
‘‘Get Ready to Take Cervical Cancer Screening to the Next
Level: Newly Approved Human Papillomavirus Test
Offers 2-in-1 Package.’’ Contraceptive Technology
Update June 2003: 61–64.
‘‘Obesity Linked to Cervical Adenocarcinoma, a HormoneDependent Cancer.’’ Cancer Weekly July 29, 2003: 59.
‘‘Study: HPV Test Is more Effective than Pap Smear for
Cervical Cancer Screening.’’ Biotech Week December
31, 2003: 143.
Van Kessel, Katherine, Koutsky, and Laura. ‘‘The
HPV Vaccine: Will it One Day Wipe Out Cervical
Cancer?’’ Contemporary OB/GYN November 2003:
71–75.
Walgate, Robert. ‘‘Vaccine Against Cervical Cancer
Passes Proof of Principle.’’ Bulletin of the
795

Cervical cancer

KEY TERMS

Cervical conization

World Health Organization January–February
2003: 73–81.
Worcester, Sharon.‘‘Smoking Tied to Poorer Outcomes in
Cervical Ca: Locally Advanced Disease.’’ Family
Practice News May 15, 2003: 29–31.

Description

OTHER

The patient lies on the table with her legs raised in
stirrups, similar to the position when having a Pap
test. The patient is given general anesthesia, and the
vagina is held open with an instrument called a speculum. Using a scalpel or laser the doctor removes a
cone-shaped piece of the cervix containing the area
with abnormal cells. The resulting crater is repaired
by stitching flaps of tissue over the wound.
Alternatively, the wound may be left open, and heat
or freezing is used to stop bleeding.

‘‘Cancer of the Cervix.’’ CancerNet. 12 Dec. 2000. National
Cancer Institute. NIH Publication No. 95-2047. April
3, 2001. <http://cancernet.nci.nih.gov/wyntk_pubs/
cervix.htm#2>.
‘‘Cervical Cancer.’’ Cancer Resource Center. American
Cancer Society. Mar 16, 2000. [cited April 3, 2001].
<http://www3.cancer.org/cancerinfo/load_cont.asp?ct
=8&doc=25&Language=English>.

Once the tissue has been removed, it is examined
under a microscope for signs of cancer. If cancer is
present, other tests will be needed. Surgery will be
performed to remove the cervix and uterus (hysterectomy) and other treatments may be used as well. If the
abnormal cells are precancerous, a laser can be used to
destroy them.

ORGANIZATIONS

Eyes On The Prize. Org. 446 S. Anaheim Hills Road,
#108, Anaheim Hills, CA 92807. <http://www.eyesontheprize.org>. On-line information and emotional
support for women with gynecologic cancer.

Lata Cherath, PhD
Margaret Alic, PhD
Teresa G. Odle

I Cervical conization
Definition
Cervical conization is both a diagnostic and treatment tool used to detect and treat abnormalities of the
cervix. It is also known as a cone biopsy or cold knife
cone biopsy.

Purpose
Cervical conization is performed if the results of a
cervical biopsy have found a precancerous condition
in the cervix. The cervix is the small cylindrical organ
at the lower part of the uterus, which separates the
uterus from the vagina. Cervical conization also may
be performed if there is an abnormal cervical smear
test (Pap test). A biopsy is a diagnostic test in which
tissue or cells are removed from the body and examined under a microscope, primarily to look for cancer
or other abnormalities.

Precautions
As with any operation that is performed under
general anesthesia, the patient must not eat or drink
anything for six to eight hours before surgery.
796

Cold knife cone biopsy used to be the preferred
treatment for removing abnormal cells in the cervix.
Now, most cone biopsies are performed using laser
surgery. Cold knife cone biopsy is generally used only
for special situations. For example, if a biopsy did not
remove all the abnormal cells, the cold knife cone procedure allows the physician to remove what’s left.

Aftercare
An overnight stay in the hospital may be required.
After the test, the patient may feel some cramps or
discomfort for about a week. Women should not have
sex, use tampons, or douche until after seeing their
physician for a follow up appointment (a week or
more after the procedure).

Risks
Because cone biopsies carry risks such as bleeding
and problems with subsequent pregnancies, they have
been replaced with newer technologies except in a few
circumstances.
About one in 10 women experience bleeding from
the vagina about two weeks after the biopsy. There is
also a slight risk of infection or perforation of the
uterus. In a few women, the cervical canal becomes
narrowed or completely blocked, which can later
interfere with the movement of sperm. This can impair
a woman’s fertility.
If too much muscle tissue has been removed, the
procedure can lead to an incompetent cervix, which can
be a problem with subsequent pregnancies. An incompetent cervix cannot seal properly to maintain a
GALE ENCYCLOPEDIA OF MEDICINE

Biopsy—The removal of a small piece of living
tissue for examination under a microscope.
Pap test—The short term for Papanicolaou test, this
procedure tests a smear of cellular material scraped
from the cervix and examined under a microscope
to detect abnormal cells.

pregnancy. If untreated, the condition increases the
odds of miscarriage or premature labor.
Cervical conization also may temporarily alter
cervical cells, which can make a Pap smear test hard
to interpret accurately for three or four months.

Normal results
This procedure is only performed if an abnormality is known or suspected.

Abnormal results
The presence of precancerous or cancerous cells in
the cervix.
Resources
ORGANIZATIONS

Cancer Information Service. 9000 Rockville Pike, Building
31, Suite 10A18, Bethesda, MD 20892. 1-800-4CANCER. <http://wwwicic.nci.nih.gov>.

Carol A. Turkington

I Cervical disk disease
Definition
Cervical disk disease refers to a gradual deterioration of the spongy disks in the top part of the spine.

Cervical disk disease affects everyone to some
degree, often without causing any bothersome symptoms. However, this condition can also lead to specific
problems related to nerve functioning. For example,
the outer edge of a disk may tear, allowing the gelatinous material inside to bulge outward (herniated disk).
This can put pressure on nerves that exit the spine.
Two adjacent vertebrae may rub together (sometimes
resulting in bone spurs) that can also pinch these
nerves. In other cases, the inner part of the ring may
push on the spinal cord itself, which passes through
the disk. Any of these situations can cause pain and
limit movement. While symptoms primarily affect the
neck, they can also occur in other parts of the body.

Causes and symptoms
Cervical disk disease is a gradual process that
occurs with aging, though poor posture, repeated lifting, and tobacco use can hasten its course. Symptoms
include pain when moving the neck and limited neck
movement. The condition can also affect the hand,
shoulder, and arm resulting in pain, numbness/tingling, and weakness. If the spinal cord itself is affected,
these symptoms may occur in the legs. Loss of bowel
or bladder control may also occur.

Diagnosis
Cervical disk disease is typically diagnosed by an
orthopedist or a neurologist. After taking a medical
history and conducting a physical examination, the
doctor will recommend an imaging procedure to
gather more information about the nature of the problem. This may include a CT scan, an MRI, or myelography. In addition, an electromyogram (EMG) may
be used to evaluate the functioning of nerves in the
arms, hands, or legs. Cervical disk disease is typically
covered by medical insurance.

Treatment
Description
The spine is made up of 33 bones called vertebrae
separated by spongy rings of elastic material. These
rings, known as disks, are often compared to shock
absorbers because they help to cushion the vertebrae.
Just as importantly, they also make it possible to turn the
head and neck. Over time, these disks slowly become
GALE ENCYCLOPEDIA OF MEDICINE

Treatment usually involves physical therapy, several
weeks of drug therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), and limited use of a cervical collar
(to reduce neck movement). Neck traction and heat
treatments may also be recommended. In some cases,
steroids or anesthetic drugs may be injected into the
spinal canal to help alleviate symptoms. Aside from
797

Cervical disk disease

KEY TERMS

flattened and less elastic due to everyday wear and tear.
When this process occurs in the disks of the neck, it is
referred to as cervical disk disease. Other general terms
for this process include degenerative disk disease and
intervertebral disk disease.

Cervical spondylosis

Resources

KEY TERMS
Bone spur—An overgrowth of bone.
Cervical—Relating to the top part of the spine that
is composed of the seven vertebrae of the neck and
the disks that separate them.
Computed tomography (CT) scan—An imaging
procedure that produces a three-dimensional picture of organs or structures inside the body.
Myelography—An imaging procedure involving
the injection of a radioactive dye into the fluid
surrounding the spine. A myelography can be
used to detect herniated disks, nerve root damage,
and other problems affecting the cervical spine.
Neurologist—A doctor who specializes in disorders of the brain and central nervous system.
Orthopedist—A doctor who specializes in disorders of the musculoskeletal system.
Magnetic resonance imaging—A type of imaging
that uses magnetic fields to generate a picture of
internal structures.

these measures, maintaining good posture and placing a
pillow under the neck and head during sleep can be
helpful. Treatment may last anywhere from several
weeks to three months or more. Neck surgery is not
usually advised unless other therapies have failed.

Alternative treatment
Acupuncture, therapeutic massage, and yoga are
believed by some practitioners of alternative medicine
to have generalized pain-relieving effects. However,
any therapy that involves manipulating the neck is
not recommended and be approved by primary doctor
beforehand.

Prognosis
In most people symptoms go away within three
months if not sooner. A smaller number may require
surgery to correct the problem.

Prevention
While some degree of disk degeneration is inevitable, people can reduce their risk by practicing good
posture (during sitting, standing, and lifting), performing neck-stretching exercises, maintaining an
ideal weight, and quitting smoking.
798

PERIODICALS

Heckmann, J. G., et al. ‘‘Herniated Cervical Intervertebral
Discs with Radiculopathy: An Outcome Study of
Conservatively or Surgically Treated Patients.’’ Journal
of Spinal Disorders 12 (October 1999): 396-401.
ORGANIZATIONS

American Academy of Orthopaedic Surgeons. 6300 North
River Road, Rosemont, IL 60018-4262. (800) 346-2267.
<http://www.aaos.org>.

Greg Annussek

Cervical osteoarthritis see Cervical
spondylosis

I Cervical spondylosis
Definition
Cervical spondylosis refers to common agerelated changes in the area of the spine at the back of
the neck. With age, the vertebrae (the component
bones of the spine) gradually form bone spurs, and
their shock-absorbing disks slowly shrink. These
changes can alter the alignment and stability of the
spine. They may go unnoticed, or they may produce
problems related to pressure on the spine and associated nerves and blood vessels. This pressure can
cause weakness, numbness, and pain in various areas
of the body. In severe cases, walking and other activities may be compromised.

Description
As it runs from the brain down the back, the
spinal cord is protected by ringlike bones, called vertebrae, stacked one upon the other. The vertebrae are
not in direct contact with one another, however. The
intervening spaces are filled with structures called
disks. The disks are made up of a tough, fibrous
outer tissue with an inner core of elastic or gel-like
tissue.
One of the most important functions of disks is
protecting the vertebrae and the nerves and blood vessels between the vertebrae. The disks also lend flexibility to the spinal cord, facilitating movements such as
turning the head or bending the neck. As people age,
disks gradually become tougher and more unyielding.
Disks also shrink with age, which reduces the amount
of padding between the vertebrae.
GALE ENCYCLOPEDIA OF MEDICINE

By age 50, 25–50% of people develop cervical
spondylosis; by 75 years of age, it is seen in at least
70% of people. Although shrunken vertebral disks,
osteophyte growth, and other changes in their cervical
spine may exist, many of these people never develop
significant problems.
However, about 50% of people over age 50 experience neck pain and stiffness due to cervical spondylosis.
Of these people, 25–40% have at least one episode of
cervical radiculopathy, a condition that arises when
osteophytes compress nerves between the vertebrae.
Another potential problem occurs if osteophytes,
degenerating disks, or shifting vertebrae narrow the
spinal canal. This pressure compresses the spinal cord
and its blood vessels, causing cervical spondylitic myelopathy, a disorder in which large segments of the spinal
cord are damaged. This disorder affects fewer than 5%
of people with cervical spondylosis. Symptoms of both
cervical spondylitic myelopathy and cervical radiculopathy may be present in some people.

Causes and symptoms
As people age, shrinkage of the vertebral disks
prompts the vertebrae to form osteophytes to stabilize
the back bone. However, the position and alignment
of the disks and vertebrae may shift despite the osteophytes. Symptoms may arise from problems with one
or more disks or vertebrae.
Osteophyte formation and other changes do not
necessarily lead to symptoms, but after age 50, half of
the population experiences occasional neck pain and
stiffness. As disks degenerate, the cervical spine becomes
less stable, and the neck is more vulnerable to injuries,
including muscle and ligament strains. Contact between
the edges of the vertebrae can also cause pain. In some
people, this pain may be referred–that is, perceived as
occurring in the head, shoulders, or chest, rather than
the neck. Other symptoms may include vertigo (a type
of dizziness) or ringing in the ears.
The neck pain and stiffness can be intermittent, as
can symptoms of radiculopathy. Radiculopathy refers
to compression on the base, or root, of nerves that lead
away from the spinal cord. Normally, these nerves fit
comfortably through spaces between the vertebrae.
GALE ENCYCLOPEDIA OF MEDICINE

These spaces are called intervertebral foramina. As the
osteophytes form, they can impinge on this area and
gradually make the fit between the vertebrae too snug.
The poor fit increases the chances that a minor
incident, such as overdoing normal activities, may
place excess pressure on the nerve root, sometimes
referred to as a pinched nerve. Pressure may also
accumulate as a direct consequence of osteophyte formation. The pressure on the nerve root causes severe
shooting pain in the neck, arms, shoulder, and/or
upper back, depending on which nerve roots of the
cervical spine are affected. The pain is often aggravated by movement, but in most cases, symptoms
resolve within four to six weeks.
Cervical spondylosis can cause cervical spondylitic myelopathy through stenosis- or osteophyterelated pressure on the spinal cord. Spinal stenosis is
a narrowing of the spinal canal– the area through the
center of the vertebral column occupied by the spinal
cord. Stenosis occurs because of misaligned vertebrae
and out-of-place or degenerating disks. The problems
created by spondylosis can be exacerbated if a person
has a naturally narrow spinal canal. Pressure against
the spinal cord can also be created by osteophytes
forming on the inner surface of vertebrae and pushing
against the spinal cord. Stenosis or osteophytes can
compress the spinal cord and its blood vessels, impeding or choking off needed nutrients to the spinal cord
cells; in effect, the cells starve to death.
With the death of these cells, the functions that
they once performed are impaired. These functions
may include conveying sensory information to the
brain or transmitting the brain’s commands to voluntary muscles. Pain is usually absent, but a person may
experience leg numbness and an inability to make the
legs move properly. Other symptoms can include
clumsiness and weakness in the hands, stiffness and
weakness in the legs, and spontaneous twitches in the
legs. A person’s ability to walk is affected, and a widelegged, shuffling gait is sometimes adopted to compensate for the lack of sensation in the legs and the
accompanying, realistic fear of falling. In very few
cases, bladder control becomes a problem.

Diagnosis
Cervical spondylosis is often suspected based on
the symptoms and their history. Careful neurological
examination can help determine which nerve roots are
involved, based on the location of the pain and numbness, and the pattern of weakness and changes in reflex
responses. To confirm the suspected diagnosis, and to
rule out other possibilities, imaging tests are ordered.
799

Cervical spondylosis

As the amount of padding shrinks, the spine loses
stability. The vertebrae react by constructing osteophytes, commonly known as bone spurs. There are
seven vertebrae in the neck; development of osteophytes
on these bones is sometimes called cervical osteoarthritis. Osteophytes may help to stabilize the degenerating
backbone and help protect the spinal cord.

Cervical spondylosis

The first test is an x ray. X rays reveal the presence of
osteophytes, stenosis, constricted space between the
vertebrae, and misalignment in the cervical spine–in
short, an x ray confirms that a person has cervical
spondylosis. To demonstrate that the condition is
causing the symptoms, more details are needed.
Other imaging tests, such as magnetic resonance imaging (MRI) and computed tomography myelography,
help assess effects of cervical spondylosis on associated nerve tissue and blood vessels.
An MRI may be preferred, because it is a noninvasive procedure and does not require injecting a
contrast medium as does computed tomography myelography. MRIs also have greater sensitivity for detecting disk problems and spinal cord involvement, and the
test allows the physician to create images of a larger
area from various angles. However, these images may
not show enough detail about the vertebrae themselves.
Computed tomography myelography yields a superior
image of the bones involved in cervical spondylosis.
Added benefits include that it takes less time to perform
and tends to be less expensive than an MRI. A good
diagnosis may be reached with either a computed tomography myelography or an MRI, but sometimes complementary information from both tests is necessary.
Nerve conduction velocity, electromyogram (EMG),
and/or somatosensory evoked potential testing may
help to confirm which nerve roots are involved.

Treatment
When possible, conservative treatment of symptoms is preferred. Conservative treatment begins with
rest–either restricting normal activities to a less strenuous level or bed rest for three to five days. If rest is not
adequate to relieve symptoms, a cervical orthosis may
be prescribed, such as a soft cervical collar or stiffer
neck brace to restrict neck movement and shift some of
the head’s weight from the neck to the shoulders.
Cervical traction may also be suggested, either at
home with the advice of a physical therapist or in a
health-care setting.
Pain is treated with nonsteroidal anti-inflammatory
drugs, such as aspirin or ibuprofen. If these drugs are
ineffective, a short-term prescription for corticosteroids
or muscle relaxants may be given. For chronic pain,
tricyclic antidepressants can be prescribed. Although
these drugs were developed to treat depression, they
are also effective in treating pain. Once any pain is
resolved, exercises to strengthen neck muscle and preserve flexibility are prescribed.
If the pain is severe, a short treatment of epidural
corticosteroids may be prescribed with discretion.
800

A corticosteroid such as prednisone can be combined
with an anaesthetic and injected with a long needle
into the space between the damaged disk and the
covering of the nerve and spinal cord. Injection into
the cervical epidural space relieves severe pain that is
not managed with conventional treatment. Frequent
use of this treatment is not medically recommended
and is used only if the more conservative therapy is not
effective.
If pain is continuous and does not respond to
conservative treatment, surgery may be suggested.
Surgery is usually not recommended for neck pain,
but it may be necessary to address radiculopathy and
myelopathy. Surgery is particularly recommended for
people who have already developed moderate to
severe symptoms of myelopathy, although age or
poor health may prohibit that recommendation. The
specific details of the surgery depend on the structures
involved, but the overall goal is to relieve pressure on
the nerve root, spinal cord, or blood vessels and to
stabilize the spine.

Alternative treatment
Alternative therapy is not meant to replace conventional medical treatment, but it can be a useful adjunct.
Its main roles are to relieve tension, manage pain, and
strengthen neck and back muscles. Massage is one way
to relieve tension, and yoga provides the additional
benefit of strengthening muscles. Chiropractic and acupuncture have been reported to relieve the pain associated with disk problems, although great care needs to
be taken to avoid exacerbating them. Practitioners of
the Alexander technique or the Feldenkrais method can
provide instruction on correct posture and exercise that
may help prevent further symptoms. Vitamin and
mineral supplementation along with herbal therapies
and homeopathy can help build and rebalance the weakened structure.

Prognosis
The gradual progression of cervical spondylosis
cannot be stopped; however, it doesn’t always cause
symptoms. For the individuals who do experience problems, conservative treatment is very effective in managing the symptoms. Nearly all people with neck pain,
approximately 75% of persons with radiculopathy, and
up to 50% of people with myelopathy find relief
through therapy alone. For the remaining people with
radiculopathy or myelopathy, surgery may be recommended. Surgery is deemed successful in 70–80% of
cases.
GALE ENCYCLOPEDIA OF MEDICINE

Alexander technique—A technique developed by
Frederick Alexander that focuses on the variations
in body posture, muscles, and breathing. Defects in
these functions can lead to stress, nervous tension or
possible loss of function.

Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.

Bone spur—Also called an osteophyte, it is an outgrowth or ridge that forms on a bone.
Cervical—Referring to structures within the neck.

Myelopathy—A disorder in which the tissue of the
spinal cord is diseased or damaged.
Orthosis—An external device, such as a splint or a
brace, that prevents or assists movement.

Computed tomography myelography—This medical procedure combines aspects of computed tomography scanning and plain-film myelography. A CT
scan is an imaging technique in which cross-sectional
x rays of the body are compiled to create a threedimensional image of the body’s internal structures.
Myelography involves injecting a water-soluble substance into the area around the spine to make it visible
on x rays. In computed tomography myelography or
CT myelography, the water-soluble substance is
injected, but the imaging is done with a CT scan.
Disk—A ringlike structure that fits between the vertebrae in the spine to protect the bones, nerves, and
blood vessels. The outer layer is a tough, fibrous
tissue, and the inner core is composed of more elastic tissue.
Feldenkrais method—A therapy based on creating a
good self image by correction and improvements of
body movements.

Prevention
Since cervical spondylosis is part of the normal
aging process, not much can be done to prevent it. It
may be possible to ward off some or all of the symptoms by engaging in regular physical exercise and limiting occupational or recreational activities that place
pressure on the head, neck, and shoulders. The best
exercises for the health of the cervical spine are noncontact activities, such as swimming, walking, or yoga.
Once symptoms have already developed, the emphasis
is on symptom management rather than prevention.

Osteophyte—Also referred to as bone spur, it is an
outgrowth or ridge that forms on a bone.
Radiculopathy—Sometimes referred to as a pinched
nerve, it refers to compression of the nerve root–the
part of a nerve between vertebrae. This compression
causes pain to be perceived in areas to which the
nerve leads.
Spine—A term for the backbone that includes the
vertebrae, disks, and spinal cord as a whole.
Stenosis—A condition in which a canal or other
passageway in the body is constricted.
Traction—A medical treatment that exerts a pulling
or extending force. Used for cervical problems, it
relieves pressure on structures between the vertebrae and muscular tension.
Vertebrae—The ringlike component bones of the
spine.

I Cervicitis
Definition
Cervicitis is an inflammation of the cervix.

Description
Cervicitis is a inflammation of the cervix (the
opening into the uterus). This inflammation can be
chronic and may or may not have an identified cause.

Causes and symptoms

Resources
PERIODICALS

McCormack, Bruce M., and Phillip R. Weinstein. ‘‘Cervical
Spondylosis: An Update.’’ Western Journal of Medicine
165 (July-August 1996): 43.

Julia Barrett
GALE ENCYCLOPEDIA OF MEDICINE

The most common cause of cervicitis is infection,
either local or as a result of various sexually transmitted
diseases, such as chlamydia or gonorrhea. Cervicitis can
also be caused by birth control devices such as a cervical
cap or diaphragm, or chemical exposure. Other risk
factors include multiple sexual partners or cervical
801

Cervicitis

KEY TERMS

Cesarean section

trauma following birth. In postmenopausal women,
cervicitis is sometimes related to a lack of estrogen.
Although a woman may not notice any signs
of infection, symptoms of cervicitis include the
following:


persistent unusual vaginal discharge



abnormal bleeding, either between periods or following sexual intercourse



painful sexual intercourse



vaginal pain



frequent need to urinate



burning or itching in the vaginal area

Diagnosis
The standard method of diagnosing cervicitis is
through a pelvic examination or a Pap smear. During
the pelvic exam, the physician usually swabs the
affected area, and then sends the tissue sample to a
laboratory. The laboratory tries to identify the specific
organism responsible for causing the cervicitis.
A biopsy to take a sample of tissue from the affected
area is sometimes required in order to rule out cancer.
Colposcopy, a procedure used to look at the cervix
under a microscope, may also be used to rule out
cancer.

Treatment
The first course of treatment for cervicitis is
usually antibiotics. If these medicines do not cure the
cervicitis, other treatment options include:


Loop Electrosurgical Excision Procedure (LEEP)



cryotherapy



electrocoagulation



laser treatment

KEY TERMS
Cryotherapy—Freezing the affected tissue.
Electrocoagulation—Using electrical current to
cauterize the affected tissue.
LEEP—Loop Electrosurgical Excision Procedure.

a later age have been shown to have a lower incidence
of cervicitis. Another recommendation is to use a latex
condom consistently during intercourse. If the cervicitis is caused by any sexually transmitted disease, the
patient is advised to notify all sexual partners.
Resources
BOOKS

Dambro, Mark R. The 5-Minute Clinical Consult. Baltimore:
Williams and Wilkins, 2001.
Mandell, Gerald L. Mandell, Douglas, and Bennet’s
Principles and Practice of Infectious Diseases.
Philadelphia: Churchill Livingstone, 2000.
Tierney, Lawrence, et. al. Current Medical Diagnosis and
Treatment. Los Altos: Lange Medical Publications,
2001.
PERIODICALS

Malik, S. N., et. al. ‘‘Benign Cellular Changes in Pap Smears.
Causes and Significance.’’ Acta Cytologica January–
February 2001: 5-8.
ORGANIZATIONS

American College of Obstetricians and Gynecologists.
409 12th Street, SW P.O. Box 96920, Washington, DC
20090-6920. (202) 863-2518. <http://
www.acog.org>.

Kim A. Sharp, M.Ln.

Prognosis
Cervicitis will usually be cured when the course
of therapy is complete. Severe cases, however, may
last for a few months, even after the therapy is complete. If the cervicitis was caused by a sexually transmitted disease, both partners should be treated with
medication.

I Cesarean section
Definition
A cesarean section is a surgical procedure in which
incisions are made through a woman’s abdomen and
uterus to deliver her baby.

Prevention
Practicing safe sexual behavior, such as monogamy, is one way of lowering the prevalence of cervicitis. In addition, women who began sexual activity at
802

Purpose
Cesarean sections, also called c-sections, are performed whenever abnormal conditions complicate
GALE ENCYCLOPEDIA OF MEDICINE

Difficult labor is commonly caused by one of the
three following conditions: abnormalities in the
mother’s birth canal; abnormalities in the position of
the fetus; or abnormalities in the labor, including weak
or infrequent contractions.
Another major factor is fetal distress, a condition
where the fetus is not getting enough oxygen. Fetal
brain damage can result from oxygen deprivation.
Fetal distress is often related to abnormalities in the
position of the fetus or abnormalities in the birth
canal, causing reduced blood flow through the placenta. Other conditions also can make c-section advisable, such as vaginal herpes, hypertension, and
diabetes in the mother.

Precautions
There are several ways that obstetricians and
other doctors diagnose conditions that may make a
c-section necessary. Ultrasound testing reveals the
positions of the baby and the placenta and may be
used to estimate the baby’s size and gestational age.
Fetal heart monitors, in use since the 1970s, transmit
any signals of fetal distress. Oxygen deprivation may
be determined by checking the amniotic fluid for
meconium (feces)—a lack of oxygen causes an unborn
baby to defecate. Oxygen deprivation may also be
determined by testing the pH of a blood sample
taken from the baby’s scalp; a pH of 7.25 or higher is
normal, between 7.2 and 7.25 is suspicious, and below
7.2 is a sign of trouble.
When a c-section is being considered because
labor is not progressing, the mother should first be
encouraged to walk around to stimulate labor. Labor
may also be stimulated with the drug oxytocin.
When a c-section is being considered because
the baby is in a breech position, the doctor may
first attempt to reposition the baby; this is called
external cephalic version. The doctor may also try
a vaginal breech delivery, depending on the size of
the mother’s pelvis, the size of the baby, and the
type of breech position the baby is in. However, a
c-section is safer than a vaginal delivery when the
baby is 8 lbs (3.6 kg) or larger, in a breech position
with the feet crossed, or in a breech position with the
head hyperextended.
GALE ENCYCLOPEDIA OF MEDICINE

A woman should receive regular prenatal care and
be able to alert her doctor to the first signs of trouble.
Once labor begins, she should be encouraged to move
around and to urinate. The doctor should be conservative in diagnosing dystocia (nonprogressive labor)
and fetal distress, taking a position of ‘‘watchful waiting’’ before deciding to operate.

Description
The most common reason that a cesarean section
is performed (in 35% of all cases, according to the
United States Public Health Service) is that the
woman has had a previous c-section. The ‘‘once a
cesarean, always a cesarean’’ rule originated when
the classical uterine incision was made vertically; the
resulting scar was weak and had a risk of rupturing in
subsequent deliveries. Today, the incision is almost
always made horizontally across the lower end of the
uterus (this is called a ‘‘low transverse incision’’),
resulting in reduced blood loss and a decreased
chance of rupture. This kind of incision allows
many women to have a vaginal birth after a cesarean
(VBAC).
The second most common reason that a c-section
is performed (in 30% of all cases) is difficult childbirth due to nonprogressive labor (dystocia). Uterine
contractions may be weak or irregular, the cervix
may not be dilating, or the mother’s pelvic structure
may not allow adequate passage for birth. When the
baby’s head is too large to fit through the pelvis,
the condition is called cephalopelvic disproportion
(CPD).
Another 12% of c-sections are performed to deliver a baby in a breech presentation: buttocks or feet
first. Breech presentation is found in about 3% of all
births.
In 9% of all cases, c-sections are performed in
response to fetal distress. Fetal distress refers to any
situation that threatens the baby, such as the umbilical
cord getting wrapped around the baby’s neck. This
may appear on the fetal heart monitor as an abnormal
heart rate or rhythm.
The remaining 14% of c-sections are indicated by
other serious factors. One is prolapse of the umbilical
cord: the cord is pushed into the vagina ahead of the
baby and becomes compressed, cutting off blood flow
to the baby. Another is placental abruption: the placenta separates from the uterine wall before the baby is
born, cutting off blood flow to the baby. The risk of
this is especially high in multiple births (twins, triplets,
or more). A third factor is placenta previa: the placenta
803

Cesarean section

labor and vaginal delivery, threatening the life or health
of the mother or the baby. In 2003, about 27% of U.S.
deliveries were cesarean, up 6% from 2002. The procedure is often used in cases where the mother has had a
previous c-section. Dystocia, or difficult labor, is the
other common cause of c-sections.

Cesarean section
This baby is being delivered by cesarean section. (Photograph by John Smith, Custom Medical Stock Photo.)

covers the cervix partially or completely, making
vaginal delivery impossible. In some cases requiring
c-section, the baby is in a transverse position, lying
horizontally across the pelvis, perhaps with a
shoulder in the birth canal.
The mother’s health may make delivery by c-section the safer choice, especially in cases of maternal
diabetes, hypertension, genital herpes, Rh blood
incompatibility, and preeclampsia (high blood pressure related to pregnancy).

Preparation
When a c-section becomes necessary, the mother
is prepped for surgery. A catheter is inserted into her
bladder and an intravenous (IV) line is inserted into
her arm. Leads for monitoring the mother’s heart rate,
rhythm, and blood pressure are attached. In the operating room, the mother is given anesthesia—usually a
regional anesthetic (epidural or spinal), making her
numb from below her breasts to her toes. In some
cases, a general anesthetic will be administered.
Surgical drapes are placed over the body, except the
804

head; these drapes block the direct view of the
procedure.
The abdomen is washed with an anti-bacterial
solution and a portion of the pubic hair may be
shaved. The first incision opens the abdomen.
Infrequently, it will be vertical from just below the
navel to the top of the pubic bone, or more commonly,
it will be a horizontal incision across and above the
pubic bone (informally called a ‘‘bikini cut’’).
The second incision opens the uterus. In most
cases a transverse incision is made. This is the favored
type because it heals well and makes it possible for a
woman to attempt a vaginal delivery in the future. The
classical incision is vertical. Because it provides a larger opening than a low transverse incision, it is used in
the most critical situations, such as placenta previa.
However, the classical incision causes more bleeding, a
greater risk of abdominal infection, and a weaker scar,
so the low transverse incision is preferred.
Once the uterus is opened, the amniotic sac is
ruptured and the baby is delivered. The time from
the initial incision to birth is typically five minutes.
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
A woman who undergoes a c-section requires both
the care given to any new mother and the care given to
any patient recovering from major surgery. She should
be offered pain medication that does not interfere with
breastfeeding. She should be encouraged to get out of
bed and walk around eight to 24 hours after surgery to
stimulate circulation (thus avoiding the formation of
blood clots) and bowel movement. She should limit
climbing stairs to once a day, and avoid lifting anything
heavier than the baby. She should nap as often as the
baby sleeps, and arrange for help with the housework,
meals, and care of other children. She may resume driving after two weeks, although some doctors recommend
waiting for six weeks, the typical recovery period from
major surgery.

Risks
Because a c-section is a surgical procedure, it carries more risk to both the mother and the baby. The
maternal death rate is less than 0.02%, but that is four
times the maternal death rate associated with vaginal
delivery. However, many women have a c-section for
serious medical problems. The mother is at risk for
increased bleeding (because a c-section may result in
twice the blood loss of a vaginal delivery) from the two
incisions, the placental attachment site, and possible
damage to a uterine artery. Complications occur in
less than 10% of cases. The mother may develop infection of either incision, the urinary tract, or the tissue
lining the uterus (endometritis). Less commonly, she
may receive injury to the surrounding organs, like the
bladder and bowel. When a general anesthesia is used,
she may experience complications from the anesthesia.
A 2004 report said that spinal anesthesia and obesity
impair a mother’s respiratory function during cesarean section procedures. Obese women were particularly susceptible to breathing problems. Very rarely, a
woman may develop a wound hematoma at the site of
either incision or other blood clots leading to pelvic
thrombophlebitis (inflammation of the major vein running from the pelvis into the leg) or a pulmonary
embolus (a blood clot lodging in the lung).
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Breech presentation—The condition in which the
baby enters the birth canal with its buttocks or feet
first.
Cephalopelvic disproportion (CPD)—The condition in which the baby’s head is too large to fit
through the mother’s pelvis.
Classical incision—In a cesarean section, an incision made vertically along the uterus; this kind of
incision makes a larger opening but also creates
more bleeding, a greater chance of infection, and
a weaker scar.
Dystocia—Failure to progress in labor, either
because the cervix will not dilate (expand) further
or (after full dilation) the head does not descend
through the mother’s pelvis.
Low transverse incision—Incision madehorizontally
across the lower end of the uterus; this kind of incision
is preferred for less bleeding and stronger healing.
Placenta previa—The placenta totally or partially
covers the cervix, preventing vaginal delivery.
Placental abruption—Separation of the placenta
from the uterine wall before the baby is born, cutting off blood flow to the baby.
Prolapsed cord—The umbilical cord is pushed into
the vagina ahead of the baby and becomes compressed, cutting off blood flow to the baby.
Respiratory distress syndrome (RDS)—Difficulty
breathing, found in infants with immature lungs.
Transverse presentation—The baby is laying sideways across the cervix instead of head first.
VBAC—Vaginal birth after cesarean.

Normal results
The after-effects of a c-section vary, depending on
the woman’s age, physical fitness, and overall health.
Following this procedure, a woman commonly experiences gas pains, incision pain, and uterine contractions—which are also common in vaginal delivery.
Her hospital stay may be two to four days. Breastfeeding the baby is encouraged, taking care that it is in
a position that keeps the baby from resting on the
mother’s incision. As the woman heals, she may gradually increase appropriate exercises to regain abdominal
tone. Full recovery may be seen in four to six weeks.
The prognosis for a successful vaginal birth after a
cesarean (VBAC) may be at least 75%, especially
805

Cesarean section

Once the umbilical cord is clamped and cut, the
newborn is evaluated. The placenta is removed from
the mother, and her uterus and abdomen are stitched
closed (surgical staples may be used instead in closing
the outermost layer of the abdominal incision). From
birth through suturing may take 30–40 minutes. Thus
the entire surgical procedure may be performed in less
than one hour.

Chagas’ disease

when the c-section involved a low transverse incision
in the uterus and there were no complications during
or after delivery.

Abnormal results
Of the hundreds of thousands of women in the
United States who undergo a c-section each year,
about 500 die from serious infections, hemorrhaging,
or other complications. These deaths may be related to
the health conditions that made the operation necessary, and not simply to the operation itself. New
research in 2004 reported that c-section delivery
affects the amount of breast milk an infant may receive
from its mother for the first five days following birth.
This can result in lower post-birth weighs as well. But
the study found that by the sixth day, mother who had
delivered by c-section began to produce milk at the
same rate as those who delivered vaginally.
Undergoing a c-section may also inflict psychological distress on the mother, beyond hormonal mood
swings and postpartum depression (‘‘baby blues’’). The
woman may feel disappointment and a sense of failure
for not experiencing a vaginal delivery. She may feel
isolated if the father or birthing coach is not with her in
the operating room, or if she is treated by an unfamiliar
doctor rather than by her own doctor or midwife. She
may feel helpless from a loss of control over labor and
delivery with no opportunity to actively participate. To
overcome these feelings, the woman must understand
why the c-section was necessary. She must accept that
she couldn’t control the unforeseen events that made
the c-section the optimum means of delivery, and recognize that preserving the health and safety of both her
and her child was more important than her delivering
vaginally. Women who undergo a c-section should
be encouraged to share their feelings with others.
Hospitals can often recommend support groups for
such mothers. Women should also be encouraged to
seek professional help if negative emotions persist.
Resources
PERIODICALS

‘‘Cesarean Affects Breast Milk Intake.’’ Mothering
July–August 2004: 24.
‘‘Spinal Anesthesia, Obesity Impair Maternal Breathing
During Cesarean Section.’’ Life Science Weekly
September 28, 2004: 916.
ORGANIZATIONS

American Academy of Family Physicians. 8880 Ward
Parkway, Kansas City, MO 64114. (816) 333-9700.
<http://www.aafp.org>.
Childbirth Org. <http://www.childbirth.org>.
806

International Cesarean Awareness Network. 1304 Kingsdale
Ave., Redondo Beach, CA 90278. (310) 542-6400.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914)
428-7100. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Institute of Child Health and Human
Development. Bldg 31, Room 2A32, MSC 2425,
31 Center Drive, Bethesda, MD 20892-2425. (800)
505-2742. <http://www.nichd.nih.gov/sids/sids.htm>.
United States Department of Health and Human Services.
200 Independence Avenue SW, Washington DC 20201.
(202) 619-0257. <http://www.hhs.gov>.
OTHER

‘‘Cesarean Childbirth.’’ Perspectives: A Mental Health
Magazine. <http://mentalhelp.net/perspectives>.

Bethany Thivierge
Teresa G. Odle

Cestodiasis see Tapeworm diseases
CFS see Chronic fatigue syndrome
CGD see Chronic granulomatous disease

I Chagas’ disease
Definition
Chagas’ disease is named after Dr. Carlos Chagas
who first found the organism in the early 1900s. It
involves damage to the nerves that control the heart,
digestive and other organs, and eventually leads to
damage to these organs. Worldwide, Chagas’ disease
affects over 15 million persons, and kills 50,000 each
year. Researchers believe that the parasite that causes
the disease is only found in the Americas.

Description
When a person is infected with Chagas’ disease, the
parasite known as Trypanosoma cruzi first causes a mild,
short-lived period of ‘‘acute’’ illness; then after a long
period without symptoms, the effects of the infection
begin to appear. The heart, esophagus, and colon are
most frequently involved. These organs become unable
to contract properly, and begin to stretch or dilate.

Causes and symptoms
T. cruzi is carried by insects or bugs known as
reduviid or ‘‘kissing bugs.’’ These insects are very common in Central and South America where they inhabit
GALE ENCYCLOPEDIA OF MEDICINE

There are three phases related to infection:


Acute phase lasts about two months, with nonspecific symptoms of low grade fever, headache, fatigue, and enlarged liver or spleen.



Indeterminate phase lasts 10–20 years, during which
time no symptoms occur, but the parasites are reproducing in various organs.



Chronic phase is the stage when symptoms related to
damage of major organs (heart, esophagus, colon)
begin.

KEY TERMS
Achalasia—An esophageal disease of unknown
cause, in which the lower sphincter or muscle is
unable to relax normally, and leads to the accumulation of material within the esophagus.
Endoscopy—Exam using an endoscope (a thin flexible tube which uses a lens or miniature camera to
view various areas of the gastrointestinal tract).
When the procedure is performed to examine certain organs such as the bile ducts or pancreas, the
organs are not viewed directly, but rather indirectly
through the injection of x ray.
Parasite—An organism that lives on or in another
and takes nourishment (food and fluids) from that
organism.
Regurgitation—Flow of material back up the esophagus and into the throat or lungs.

In the chronic phase, irregularities of heart
rhythm, heart failure, and blood clots cause weakness,
fainting, and even sudden death.
Esophageal symptoms are related to difficulty with
swallowing and chest pain. Because the esophagus does
not empty properly, food regurgitates into the lungs
causing cough, bronchitis, and repeated bouts of pneumonia. Inability to eat, weight loss, and malnutrition
become a significant factor in affecting survival.
Involvement of the large intestine (colon) causes
constipation, distention, and abdominal pain.

Diagnosis
The best way to diagnose acute infection is to
identify the parasites in tissue or blood. Occasionally
it is possible to culture the organism from infected
tissue, but this process usually requires too much
time to be of value. In the chronic phase, antibody
levels can be measured. Efforts to develop new, more
accurate tests are ongoing.

Treatment
In most cases treatment of symptoms is all that is
possible. Present medications can reduce the duration
and severity of an acute infection, but are only 50%
effective, at best, in eliminating the organisms.
Cardiac effects are managed with pacemakers and
medications. Esophageal complications require either
endoscopic or surgical methods to improve esophageal emptying, similar to those used to treat the disorder known as achalasia. Constipation is treated by
GALE ENCYCLOPEDIA OF MEDICINE

increasing fiber and bulk laxatives, or removal of diseased portions of the colon.

Prognosis
Those patients with gastrointestinal complications often respond to some form of treatment.
Cardiac problems are more difficult to treat, particularly since transplant would rekindle infection.

Prevention
Visitors traveling to areas of known infection
should avoid staying in mud, adobe, or similar huts.
Mosquito nets and insect repellents are useful in helping to avoid contact with the bugs. Blood screening is
not always effective in many regions where infection is
common. It is necessary to carefully screen people who
have emigrated from Central and South America
before they make blood donations.
Resources
OTHER

Centers for Disease Control. <http://www.cdc.gov/
nccdphp/ddt/ddthome.htm>.

David Kaminstein, MD

Chalazion see Eyelid disorders
807

Chagas’ disease

poorly constructed houses and huts. The insects deposit
their waste material, exposing inhabitants to the parasites. The parasites then enter the body by way of a cut
or via the eyes or mouth. T. cruzi can also be transmitted by blood transfusion. Eating uncooked, contaminated food or breastfeeding can also transmit the
disease. The reduviids, in turn, become infected with
the parasite by biting infected animals and humans.

Chancroid

I Chancroid
Definition
Chancroid is a sexually transmitted disease caused
by a bacterial infection that is characterized by painful
sores on the genitals.

Description
Chancroid is an infection of the genitals that is
caused by the bacterium Haemophilus ducreyi.
Chancroid is a sexually transmitted disease, which
means that it is spread from person to person almost
always by sexual contact. However, there have been a
few cases in which healthcare providers have become
infected through contact with infected patients.
Common locations for chancroid sores (ulcers)
in men are the shaft or head of the penis, foreskin,
the groove behind the head of the penis, the opening
of the penis, and the scrotum. In women, common
locations are the labia majora (outer lips), labia
minora (inner lips), perianal area (area around the
anal opening), and inner thighs. It is rare for the
ulcer(s) to be on the vaginal walls or cervix. In
about 50% of the patients with chancroid, the infection spreads to either or both of the lymph nodes in
the groin.
Chancroid is most commonly found in developing and third world countries. In the United States,
the most common cause of genital ulcers is genital
herpes, followed by syphilis, and then chancroid.
As of 1997, there were fewer than 1,500 cases of
chancroid in the United States per year and it
occurred primarily in African Americans, Hispanic
Americans, and Native Americans. There are occasional localized outbreaks of chancroid in the United
States. In addition, the practice of exchanging sex for
drugs has lead to a link between crack cocaine use and
chancroid.
Even though the incidence of chancroid in the
United States decreased in the 1990s, there is an alarming connection between chancroid and human
immunodeficiency virus (HIV) infection. HIV causes
AIDS (acquired immunodeficiency syndrome) and is
easily spread from person to person through chancroid ulcers. Uncircumcised men with chancroid
ulcers have a 48% risk of acquiring HIV from sexual
contact. Women with chancroid ulcers are also at a
greater risk of being infected with HIV during sexual
contact. Genital ulcers seem to act as doorways for
HIV to enter and exit.
808

A close-up view of a chancroid specimen. (Custom Medical
Stock Photo. Reproduced by permission.)

Causes and symptoms
Haemophilus ducreyi is spread from person to person by vaginal, anal, and oral sexual contact.
Uncircumcised men are about three times more likely
than circumcised men to become infected following
exposure to Haemophilus ducreyi. Having unprotected
sex, exchanging sex for drugs, and having unprotected
sex with a prostitute are other risk factors. Many cases
of chancroid in the United States occur in persons who
had traveled to countries where the disease is more
common.
Chancroid occurs when Haemophilus ducreyi
penetrates the skin through an injury, like a scratch
or cut. Once past the skin surface, the warmth, moisture, and nutrients allow bacteria to grow rapidly. The
first sign of chancroid is a small, red papule that occurs
within three to seven days following exposure to the
bacteria, but may take up to one month. Usually
within one day, the papule becomes an ulcer. The
chancroid ulcer is painful, bleeds easily, drains a grey
or yellowish pus, and has sharply defined, ragged
edges. They can vary in size from an eighth of an
inch to two inches in diameter. Men usually have
only one ulcer, but women often have four or more.
Sometimes ‘‘kissing’’ ulcers occur when one ulcer
spreads the bacterial infection to an opposite skin surface. For example, kissing ulcers can form on the lips
of the labia majora. Alternatively, women may not
have any external sores but may experience painful
urination, intercourse, and/or bowel movements and
may have a vaginal discharge or rectal bleeding.
Signs that the infection has spread to the lymph
node appear about one week after the formation of the
genital ulcer. Lymph nodes are small organs in the
lymphatic system that filter waste materials from nearly
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Chancroid may be diagnosed and treated by urologists (urinary tract doctors for men), gynecologists (for
women), and infectious disease specialists. Part of the
diagnosis of chancroid involves ruling out genital
herpes and syphilis because genital ulcers are also symptoms of these diseases. The appearance of these three
diseases can be close enough to be confusing. However,
the presence of a pus-filled lump in the groin of a patient
with a genital ulcer is highly specific for chancroid.
For a clear-cut diagnosis of chancroid, Haemophilus
ducreyi must be isolated from the ulcer. To do this, a
sterile cotton swab is wiped over the ulcer to obtain a pus
sample. In the laboratory, the sample is put into special
media and placed in an incubator. Haemophilus ducreyi
takes from two to five days to grow in the laboratory. In
addition, the pus may be examined under the microscope to see which bacteria are in the ulcer. A sample
of the pus may also be tested to see if the herpes virus is
present. A blood sample will probably be taken from the
patient’s arm to test for the presence of antibodies to the
bacteria that causes syphilis.

KEY TERMS
Bubo—A tender, swollen lymph node in the groin
that may follow a chancroid ulcer.
Groin—The region of the body that lies between
the abdomen and the thighs.

antibiotic treatment. Severe ulcers may cause permanent scars. Severe scarring of the foreskin may require
circumcision. Urethral fistulas (abnormal passageways from the urine tube to the skin) may occur and
requires corrective surgery.

Prevention
The best prevention for chancroid is to use a condom during sexual intercourse. Chancroid can also be
prevented by abstinence (avoidance of any sexual contact) and by being in a monogamous relationship with
a disease-free partner. To prevent the spread of chancroid, it is important that all sexual contacts of the
patient are identified and treated.
Resources
ORGANIZATIONS

Planned Parenthood Federation of America, Inc. 810
Seventh Ave., New York, NY,10019. (800) 669-0156.
<http://www.plannedparenthood.org>.

Treatment
The only treatment for chancroid is antibiotics
given either once or for several days. Antibiotics
taken by mouth for one to two weeks include erythromycin (E-Mycin, Ery-Tab), amoxicillin plus clavulanic acid (Augmentin), co-trimoxazole (Bactrim,
Septra), or ciprofloxacin (Cipro). Antibiotics given in
one dose include ceftriaxone (Rocephin), spectinomycin (Trobicin), co-trimoxazole, or ofloxacin (Floxin).
The ulcer(s) may be cleaned and soaked to reduce
the swelling. Salt solution dressings may be applied to
the ulcer(s) to reduce the spread of the bacteria and
prevent additional ulcers. A serious infection of the
foreskin may require circumcision. Pus would be removed from infected lymph nodes by using a needle and
syringe. Very large buboes may require surgical drainage.

Prognosis
Without treatment, chancroid may either go away
quickly or patients may experience the painful ulcers
for many months. A complete cure is obtained with
GALE ENCYCLOPEDIA OF MEDICINE

Belinda Rowland, PhD

Change of life see Menopause
Character disorders see Personality disorders

I Charcoal, activated
Definition
Activated charcoal is a fine black odorless and
tasteless powder made from wood or other materials
that have been exposed to very high temperatures in an
airless environment. It is then treated, or activated, to
increase its ability to adsorb various substances by
reheating with oxidizing gas or other chemicals to
break it into a very fine powder. Activated charcoal
is pure carbon specially processed to make it highly
adsorbent of particles and gases in the body’s digestive
system.
809

Charcoal, activated

every organ in the body. This lymph node infection is
called ‘‘lymphadenitis’’ and the swollen, painful lymph
node is called a ‘‘bubo.’’ The bubo, which appears as a
red, spherical lump, may burst through the skin, releasing a thick pus and forming another ulcer.

Charcoal, activated

Activated charcoal has often been used since
ancient times to cure a variety of ailments including
poisoning. Its healing effects have been well documented since as early as 1550 B.C. by the Egyptians.
However, charcoal was almost forgotten until
15 years ago when it was rediscovered as a wonderful
oral agent to treat most overdoses and toxins.

Description
Activated charcoal’s most important use is for
treatment of poisoning. It helps prevent the absorption of most poisons or drugs by the stomach and
intestines. In addition to being used for most swallowed poisons in humans, charcoal has been effectively used in dogs, rabbits, rats, and other animals,
as well. It can also adsorb gas in the bowels and has
been used for the treatment of gas or diarrhea.
Charcoal’s other uses such as treatment of viruses,
bacteria, bacterial toxic byproducts, snake venoms
and other substances by adsorption have not been
supported by clinical studies. By adding water to the
powder to make a paste, activated charcoal can be
used as an external application to alleviate pain and
itching from bites and stings.
Poisons and drug overdoses
It is estimated that one million children accidentally overdose on drugs mistaken as candies or
eat, drink, or inhale poisonous household products
each year. Infants and toddlers are at the greatest
risk for accidental poisoning. Activated charcoal
is one of the agents most commonly used for these
cases. It can absorb large amounts of poisons
quickly. In addition, it is non-toxic, may be stored
for a long time, and can be conveniently administered at home. Charcoal works by binding to irritating or toxic substances in the stomach and
intestines. This prevents the toxic drug or chemical
from spreading throughout the body. The activated
charcoal with the toxic substance bound to it is
then excreted in the stool without harm to the
body. When poisoning is suspected the local poison
control center should be contacted for instructions.
They may recommend using activated charcoal,
which should be available at home so that it can
be given to the poisoned child or pet immediately.
For severe poisoning, several doses of activated
charcoal may be needed.
Activated charcoal is also used to induce vomiting
in adults who have attempted suicide by taking an
overdose of antidepressants, barbiturates, or benzodiazepine tranquilizers.
810

Intestinal disorders
In the past, activated charcoal was a popular
remedy for flatus (intestinal gas). Even before the discovery of America by Europeans, Native Americans
used powdered charcoal mixed with water to treat an
upset stomach. Although charcoal has been recommended as an alternative treatment for flatus, however,
studies done in the early 2000s have reported that it is
not particularly useful in treating intestinal gas. Such
other measures as dietary changes or biofeedback training are more effective in relieving patients’ symptoms.
Charcoal has also been used to treat such other
intestinal disorders as diarrhea, constipation, and
cramps. There are few studies to support these uses
and there are also concerns that frequent use of charcoal may decrease absorption of essential nutrients,
especially in children.
Other uses
Besides being a general antidote for poisons or
remedy for gas, activated charcoal has been used to
treat other conditions as well. Based on its ability to
adsorb or bind to other substances, charcoal has been
effectively used to clean skin wounds and to adsorb
waste materials from the gastrointestinal tract. In addition, it has been used to adsorb snake venoms, viruses,
bacteria, and harmful materials excreted by bacteria or
fungi. However, because of lack of scientific studies,
these uses are not recommended. Activated charcoal,
when used together with other remedies such as aloe
vera, acidophilus, and psyllium, helps to keep symptoms of ulcerative colitis under control. While charcoal
shows some anti-aging activity in rats, it is doubtful if it
has the same effect in humans.
Apart from its medicinal applications, activated
charcoal is used by biologists to cool cell suspensions;
by public health physicians to filter disease organisms
from drinking water; and by environmental scientists
to remove organic pollutants from ocean sediments.

Recommended dosage
For poisoning
Activated charcoal is available without prescription. In cases of accidental poisoning or drug overdose,
however, one should call an emergency poison control
center, hospital emergency room, or doctor’s office for
advice. In case that both syrup of ipecac and charcoal
are recommended for treatment of the poison, ipecac
should be given first. Charcoal should not be given for
at least 30 minutes after ipecac or until vomiting from
ipecac stops. Activated charcoal is often mixed with a
GALE ENCYCLOPEDIA OF MEDICINE

For acute poisoning, the dosage is as follows:


Infants (under 1 year of age): 1 g/kg.



Children (1–12 years of age): 15–30 g or 1–2 g/kg
with at least 8 oz of water.



Adults: 30–100 g or 1–2 g/kg with at least 8 oz of
water.
For diarrhea or gas

A person can take charcoal tablets or capsules
with water or sprinkle the content onto foods. The
dosage for treatment of gas or diarrhea in adults is
520–975 mg after each meal and up to 5 g per day.

Precautions
Parents should keep activated charcoal on hand in
case of emergencies.
Charcoal should not be given together with syrup
of ipecac. The charcoal will adsorb the ipecac.
Charcoal should be taken 30 minutes after ipecac or
after the vomiting from ipecac stops.
Some activated charcoal products contain sorbitol.
Sorbitol is a sweetener as well as a laxative, therefore, it
may cause severe diarrhea and vomiting. These products should not be used in infants.
Charcoal may interfere with the absorption of
medications and nutrients such as vitamins or minerals. For uses other than for treatment of poisoning,
charcoal should be taken two hours after other
medications.

KEY TERMS
Antidote—A remedy to counteract a poison or
injury.
Adsorption—The binding of a chemical (e.g., drug
or poison) to a solid material such as activated
charcoal or clay.
Flatus—Gas or air in the digestive tract.

Activated charcoal may cause swelling or pain in
the stomach. A doctor should be notified immediately.
It has been known to cause problems in people with
intestinal bleeding, blockage or those people who have
had recent surgery. These patients should talk to their
doctor before using this product.
Charcoal may be less effective in people with slow
digestion.
Charcoal should not be given for more than three
or four days for treatment of diarrhea. Continuing for
longer periods may interfere with normal nutrition.
Charcoal should not be used in children under
three years of age to treat diarrhea or gas.
Activated charcoal should be kept out of reach of
children.

Side effects
Charcoal may cause constipation when taken for
a drug overdose or accidental poisoning. A laxative
should be taken after the crisis is over.
Activated charcoal may cause the stool to turn
black. This side effect is to be expected.
Patients should consult a doctor if they have pain
or swelling of the stomach.

Interactions

Charcoal should not be used to treat poisoning
caused by such corrosive products as lye or other
strong acids or petroleum products such as gasoline,
kerosene, or cleaning fluids. Charcoal may make the
condition worse and delay diagnosis and treatment. In
addition, charcoal is also not effective if the poison is
lithium, cyanide, iron, ethanol, or methanol.

Activated charcoal should not be mixed with chocolate syrup, ice cream, or sherbet to make it more
palatable. These foods prevent the charcoal from
working properly.

Parents should not mix charcoal with chocolate
syrup, sherbet, or ice cream, even though it may make
charcoal taste better. These foods may prevent charcoal from working properly.

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Poisoning.’’ Section 23, Chapter 307. In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.

GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

811

Charcoal, activated

liquid before being swallowed or put into the tube
leading to the stomach. Activated charcoal is available
as 1.1 oz (33 m) liquid bottles. It is also available in
0.5 oz (15 ml) container sizes and as slurry of charcoal
pre-mixed in water or as a container to which water or
soda pop can be added. Keeping activated charcoal at
home is a good idea so that it can be taken immediately
when needed for treatment of poisoning.

Charcot Marie Tooth disease

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Psychiatric Emergencies.’’ Section 15, Chapter 194. In
The Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2002.
Cooney, David. Activated Charcoal: Antidote, Remedy, and
Health Aid. Brushton, NY: TEACH Services, Inc., 1999.
Wilson, Billie A., Margaret T. Shannon, and Carolyn L. Stang.
‘‘Charcoal, Activated (Liquid Antidote).’’ Nurses Drug
Guide 2000. Stamford, CT: Appleton & Lange, 2000.
PERIODICALS

Azpiroz, F., and J. Serra. ‘‘Treatment of Excessive Intestinal
Gas.’’ Current Treatment Options in Gastroenterology 7
(August 2004): 299–305.
Ho, K. T., R. M. Burgess, M. C. Pelletier, et al. ‘‘Use of
Powdered Coconut Charcoal as a Toxicity Identification
and Evaluation Manipulation for Organic Toxicants in
Marine Sediments.’’ Environmental Toxicology and
Chemistry 23 (September 2004): 2124–2131.
Littlejohn, C. ‘‘Management of Intentional Overdose in A &
E Departments.’’ Nursing Times 100 (August 17, 2004):
38–43.
Matsui, T., J. Kajima, and T. Fujino. ‘‘Removal Effect of the
Water Purifier for Home Use Against Cryptosporidium
parvum Oocysts.’’ Journal of Veterinary Medical
Science 66 (August 2004): 941–943.
Morris, G. J., and H. E. Richens. ‘‘Improved Methods for
Controlled Rapid Cooling of Cell Suspensions.’’ Cryo
Letters 25 (July-August 2004): 265–272.
Osterhoudt, K. C., E. R. Alpern, D. Durbin, et al.
‘‘Activated Charcoal Administration in a Pediatric
Emergency Department.’’ Pediatric Emergency Care 20
(August 2004): 493–498.
ORGANIZATIONS

American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814. (301)
657-3000. <http://www.ashp.org>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <http://www.fda.gov>.

Mai Tran
Rebecca J. Frey, PhD

I Charcot Marie Tooth disease
Definition
Charcot Marie Tooth disease (CMT) is the name
of a group of inherited disorders of the nerves in the
peripheral nervous system (nerves throughout the
body that communicate motor and sensory information to and from the spinal cord) causing weakness
and loss of sensation in the limbs.
812

Description
CMT is named for the three neurologists who first
described the condition in the late 1800s. It is also
known as hereditary motor and sensory neuropathy,
and is sometimes called peroneal muscular atrophy,
referring to the muscles in the leg that are often
affected. The age of onset of CMT can vary anywhere
from young childhood to the 50s or 60s. Symptoms
typically begin by the age of 20. For reasons yet
unknown, the severity in symptoms can also vary
greatly, even among members of the same family.
Although CMT has been described for many
years, it is only since the early 1990s that the genetic
cause of many of the types of CMT have become
known. Therefore, knowledge about CMT has
increased dramatically within a short time.
The peripheral nerves
CMT affects the peripheral nerves, those groups of
nerve cells carrying information to and from the spinal
cord. CMT decreases the ability of these nerves to carry
motor commands to muscles, especially those furthest
from the spinal cord located in the feet and hands. As a
result, the muscles connected to these nerves eventually
weaken. CMT also affects the sensory nerves that carry
information from the limbs to the brain. Therefore
people with CMT also have sensory loss. This causes
symptoms such as not being able to tell if something is
hot or cold or difficulties with balance.
There are two parts of the nerve that can be
affected in CMT. A nerve can be likened to an electrical wire, in which the wire part is the axon of the
nerve and the insulation surrounding it is the myelin
sheath. The job of the myelin is to help messages travel
very fast through the nerves. CMT is usually classified
depending on which part of the nerve is affected.
People who have problems with the myelin have
CMT type 1 and people who have abnormalities of
the axon have CMT type 2.
Specialized testing of the nerves, called nerve conduction testing (NCV), can be performed to determine
if a person has CMT1 or CMT2. These tests measure
the speed at which messages travel through the nerves.
In CMT1, the messages move too slowly, but in CMT2
the messages travel at the normal speed.

Demographics
CMT has been diagnosed in people from all over
the world. It occurs in approximately one in 2,500
people, which is about the same incidence as multiple
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
CMT is caused by changes (mutations) in any one
of a number of genes that carry the instructions to
make the peripheral nerves. Genes contain the instructions for how the body grows and develops before and
after a person is born. There are probably at least 15
different genes that can cause CMT. However, as of
early 2001, many have not yet been identified.
CMT types 1 and 2 can be broken down into
subtypes based upon the gene that is causing CMT.
The subtypes are labeled by letters, so there is
CMT1A, CMT1B, etc. Therefore, the gene with a
mutation that causes CMT1A is different from that
that causes CMT1B.
Types of CMT
CMT1A. The most common type of CMT is called
CMT1A. It is caused by a mutation in a gene called
peripheral myelin protein 22 (PMP22) located on
chromosome 17. The job of this gene is to make a
protein (PMP22) that makes up part of the myelin.
In most people who have CMT, the mutation that
causes the condition is a duplication (doubling) of
the PMP22 gene. Instead of having two copies of the
PMP22 gene (one on each chromosome) there are
three copies. It is not known how this extra copy of
the PMP22 gene causes the observed symptoms. A
small percentage of people with CMT1A do not have
a duplication of the PMP22 gene, but rather have a
point mutation in the gene. A point mutation is like a
typo in the gene that causes it to work incorrectly.
HEREDITARY NEUROPATHY WITH LIABILITY TO
PRESSURE PALSIES (HNPP). HNPP is a condition that is

also caused by a mutation in the PMP22 gene. The
mutation is a deletion. Therefore, there is only one
copy of the PMP22 gene instead of two. People who
have HNPP may have some of the signs of CMT.
However, they also have episodes where they develop
weakness and problems with sensation after compression of certain pressure points such as the elbows or
knee. Often these symptoms will resolve after a few
days or weeks, but sometimes they are permanent.
CMT1B. Another type of CMT, called CMT1B, is
caused by a mutation in a gene called myelin protein
zero (MPZ) located on chromosome 1. The job of this
gene is to make the layers of myelin stick together as
they are wrapped around the axon. The mutations in
this gene are point mutations because they involve a

GALE ENCYCLOPEDIA OF MEDICINE

change (either deletion, substitution, or insertion) at
one specific component of a gene.
CMTX. Another type of CMT, called CMTX, is
usually considered a subtype of CMT1 because it
affects the myelin, but it has a different type of inheritance than type 1 or type 2. In CMTX, the CMT–
causing gene is located on the X chromosome and is
called connexin 32 (Cx32). The job of this gene is to
code for a class of protein called connexins that form
tunnels between the layers of myelin.
CMT2. There are at least five different genes that
can cause CMT type 2. Therefore, CMT2 has subtypes
A, B, C, D and E. As of early 2001, scientists have
narrowed in on the location of most of the CMT2
causing genes. However, the specific genes and the
mutations have not yet been found for most types.
Very recently, the gene for CMT2E has been found.
The gene is called neurofilament-light (NF-L). Because
it has just been discovered, not much is known about
how mutations in this gene cause CMT.
CMT3. In the past a condition called DejerineSottas disease was referred to as CMT3. This is a
severe type of CMT in which symptoms begin in
infancy or early childhood. It is now known that this
is not a separate type of CMT and in fact people who
have onset in infancy or early childhood often have
mutations in the PMP22 or MPZ genes.
CMT4. CMT4 is a rare type of CMT in which the
nerve conduction tests have slow response results.
However, it is classified differently from CMT1 because
it is passed through families by a different pattern of
inheritance. There are five different subtypes and each
has only been described in a few families. The symptoms in CMT4 are often severe and other symptoms
such as deafness may be present. There are three different genes that have been associated with CMT4 as of
early 2001. They are called MTMR2, EGR2, and
NDRG1. More research is required to understand
how mutations in these genes cause CMT.

Inheritance
CMT1A and 1B, HNPP, and all of the subtypes of
CMT2 have autosomal dominant inheritance.
Autosomal refers to the first 22 pairs of chromosomes
that are the same in males and females. Therefore,
males and females are affected equally in these types.
In a dominant condition, only one gene of a pair needs
to have a mutation in order for a person to have
symptoms of the condition. Therefore, anyone who
has these types has a 50%, or one in two, chance of
passing CMT on to each of their children. This chance
813

Charcot Marie Tooth disease

sclerosis. It is the most common type of inherited
neurologic condition.

Charcot Marie Tooth disease

is the same for each pregnancy and does not change
based on previous children.

ground when walking. Complaints of cold legs are common, as are cramps in the legs, especially after exercise.

CMTX has X-linked inheritance. Since males only
have one X chromosome, they only have one copy of
the Cx32 gene. Thus, when a male has a mutation in
his Cx32 gene, he will have CMT. However, females
have two X chromosomes and therefore have two
copies of the Cx32 gene. If they have a mutation in
one copy of their Cx32 genes, they will only have mild
to moderate symptoms of CMT that may go unnoticed. This is because their normal copy of the Cx32
gene does make normal myelin.

In many people, the fingers and hands eventually
become affected. Muscle loss in the hands can make
fine movements such as working buttons and zippers
difficult. Some patients develop tremor in the upper
limbs. Loss of sensation can cause problems such as
numbness and the inability to feel if something is hot or
cold. Most people with CMT remain able to walk
throughout their lives.

Females pass on one or the other of their X
chromosomes to their children—sons or daughters. If
a woman with a Cx32 mutation passes her normal
X chromosome, she will have an unaffected son or
daughter who will not pass CMT on to his or her
children. If the woman passes the chromosome with
Cx32 mutation on she will have an affected son or
daughter, although the daughter will be mildly affected
or have no symptoms. Therefore, a woman with a Cx32
mutation has a 50%, or a one in two, chance of passing
the mutation to her children: a son will be affected, and
a daughter may only have mild symptoms.

Diagnosis of CMT begins with a careful neurological exam to determine the extent and distribution of
weakness. A thorough family history should be taken
at this time to determine if other people in the family
are affected. Testing may also be performed to rule out
other causes of neuropathy.

When males pass on an X chromosome, they have
a daughter. When they pass on a Y chromosome, they
have a son. Since the Cx32 mutation is on the
X chromosome, a man with CMTX will always pass
the Cx32 mutation on to his daughters. However, when
he has a son, he passes on the Y chromosome, and
therefore the son will not be affected. Therefore, an
affected male passes the Cx32 gene mutation on to all
of his daughters, but to none of his sons.
CMT4 has autosomal recessive inheritance. Males
and females are equally affected. In order for a person to
have CMT4, they must have a mutation in both of their
CMT–causing genes—one inherited from each parent.
The parents of an affected person are called carriers.
They have one normal copy of the gene and one copy
with a mutation. Carriers do not have symptoms of
CMT. Two carrier parents have a 25%, or one in four,
chance of passing CMT on to each of their children.
The onset of symptoms is highly variable, even
among members of the same family. Symptoms usually
progress very slowly over a person’s lifetime. The main
problems caused by CMT are weakness and loss of
sensation mainly in the feet and hands. The first symptoms are usually problems with the feet such as high
arches and problems with walking and running.
Tripping while walking and sprained ankles are common. Muscle loss in the feet and calves leads to ‘‘foot
drop’’ where the foot does not lift high enough off the
814

Diagnosis

A nerve conduction velocity test should be performed to measure how fast impulses travel through
the nerves. This test may show characteristic features
of CMT, but it is not diagnostic of CMT. Nerve conduction testing may be combined with electromyography (EMG), an electrical test of the muscles.
A nerve biopsy (removal of a small piece of the
nerve) may be performed to look for changes characteristic of CMT. However, this testing is not diagnostic
of CMT and is usually not necessary for making a
diagnosis.
Definitive diagnosis of CMT is made only by genetic
testing, usually performed by drawing a small amount
of blood. As of early 2001, testing is available to
detect mutations in PMP22, MPZ, Cx32 and EGR2.
However, research is progressing rapidly and new testing
is often made available every few months. All affected
members of a family have the same type of CMT.
Therefore once a mutation is found in one affected
member, it is possible to test other members who may
have symptoms or are at risk of developing CMT.
Prenatal diagnosis
Testing during pregnancy to determine whether
an unborn child is affected is possible if genetic testing
in a family has identified a specific CMT-causing
mutation. This can be done after 10–12 weeks of pregnancy using a procedure called chorionic villus sampling (CVS). CVS involves removing a tiny piece of the
placenta and examining the cells. Testing can also be
done by amniocentesis after 16 weeks gestation by
removing a small amount of the amniotic fluid surrounding the baby and analyzing the cells in the fluid.
GALE ENCYCLOPEDIA OF MEDICINE

Axon—Skinny, wire-like extension of nerve cells.
Myelin—A fatty sheath surrounding nerves in the
peripheral nervous system, which help them conduct impulses more quickly.
Nerve conduction testing—Procedure that measures the speed at which impulses move through
the nerves.
Neuropathy—A condition caused by nerve
damage. Major symptoms include weakness,
numbness, paralysis, or pain in the affected area.
Peripheral nerves—Nerves throughout the body
that carry information to and from the spinal cord.

Each of these procedures has a small risk of miscarriage associated with it, and those who are interested
in learning more should check with their doctor or
genetic counselor. Couples interested in these options
should obtain genetic counseling to carefully explore
all of the benefits and limitations of these procedures.

Treatment
There is no cure for CMT. However, physical and
occupational therapy are an important part of CMT
treatment. Physical therapy is used to preserve range
of motion and minimize deformity caused by muscle
shortening, or contracture. Braces are sometimes used
to improve control of the lower extremities that can
help tremendously with balance. After wearing braces,
people often find that they have more energy because
they are using less energy to focus on their walking.
Occupational therapy is used to provide devices and
techniques that can assist tasks such as dressing, feeding, writing, and other routine activities of daily life.
Voice-activated software can also help people who
have problems with fine motor control.

The symptoms of CMT usually progress slowly
over many years, but do not usually shorten life expectancy. The majority of people with CMT do not need
to use a wheelchair during their lifetime. Most people
with CMT are able to lead full and productive lives
despite their physical challenges.
Resources
BOOKS

Shy, M. E., J. Kamholz, and R. E. Lovelace, editors.
‘‘Charcot-Marie-Tooth Disorders.’’ Annals of the
New York Academy of Sciences. 1999.
PERIODICALS

Keller. M. P., and P. F. Chance. ‘‘Inherited peripheral neuropathies.’’ Seminars in Neurology 19, no. 4 (1999): 353–62.
Quest. A magazine for patients available from the Muscular
Dystrophy Association.
ORGANIZATIONS

Charcot Marie Tooth Association (CMTA). 2700 Chestnut
Parkway, Chester, PA 19013. (610) 499-9264 or (800)
606-CMTA. Fax: (610) 499-9267. cmtassoc@aol.com.
<www.charcot-marie-tooth.org>.
CMT International. Attn: Linda Crabtree, 1 Springbank
Dr. St. Catherine’s, ONT L2S2K1. Canada (905) 6873630. <www.cmtint.org>.
Muscular Dystrophy Association. 3300 East Sunrise
Dr., Tucson, AZ 85718. (520) 529-2000 or (800) 5721717. <http://www.mdausa.org>.
Neuropathy Association. 60 E. 42nd St. Suite 942,
New York, NY 10165. (212) 692-0662.
<www.neuropathy.org>.
OTHER

GeneClinics. University of Washington, Seattle.
<www.geneclinics.org>.
HNPP—Hereditary Neuropathy with Liability to Pressure
Palsies. <http://www.hnpp.org>.
OMIM—Online Mendelian Inheritance in Man.
<www.ncbi.nlm.nih.gov/Omim>.

Karen M. Krajewski, MS, CGC

It is very important that people with CMT avoid
injury that causes them to be immobile for long periods of time. It is often difficult for people with CMT to
return to their original strength after injury.
There is a long list of medications that should be
avoided if possible by people diagnosed with CMT
such as hydralazine (Apresoline), megadoses of vitamin A, B6, and D, Taxol, and large intravenous doses
of penicillin. Complete lists are available from the
CMT support groups. People considering taking any
of these medications should weigh the risks and benefits with their physician.
GALE ENCYCLOPEDIA OF MEDICINE

I Charcot’s joints
Definition
Charcot’s joints is a progressive degenerative disease of the joints caused by nerve damage resulting in
the loss of ability to feel pain in the joint and instability
of the joint.
815

Charcot’s joints

Prognosis

KEY TERMS

Chelation therapy

Description

Prognosis

Charcot’s joints, also called neuropathic joint disease, is the result of two conditions present in the joint.
The first factor is the inability to feel pain in the joint
due to nerve damage. The second factor is that injuries
to the joint go unnoticed leading to instability and
making the joint more susceptible to further injury.
Repeated small injuries, strains and even fractures can
go unnoticed until finally the joint is permanently
destroyed. Loss of the protective sensation of pain is
what leads to the disintegration of the joint and often
leads to deformity in the joint.

Treatment of the disease causing loss of pain perception may help to slow the damage to the joints.

Although this condition can affect any joint, the
knee is the joint most commonly involved. In individuals with diabetes mellitus, the foot is most commonly
affected. The disease can involve only one joint or it
may affect two or three joints. More than three affected
joints is very rare. In all cases, the specific joint(s)
affected depends on the location of the nerve damage.

Resnick, Donald. Diagnosis of Bone and Joint Disorders.
Philadelphia: W. B. Saunders Co., 1994.

Prevention
Preventing or effectively managing the underlying
disease can slow or in some cases reverse joint damage,
but the condition cannot be prevented.
Resources
BOOKS

Dorothy Elinor Stonely

Charley horse see Muscle spasms and
cramps

Causes and symptoms
Many diseases and injuries can interfere with the
ability to feel pain. Conditions such as diabetes mellitus, spinal injuries and diseases, alcoholism, and even
syphilis can all lead to a loss of the ability to feel pain in
some areas. Lack of pain sensation may also be
congenital.
The symptoms of Charcot’s joints can go unnoticed for some time and may be confused with osteoarthritis in the beginning. Swelling and stiffness in a
joint without the expected pain, or with less pain than
would be expected, are the primary symptoms of this
condition. As the condition progresses, however, the
joint can become very painful due to fluid build-up
and bony growths.

Diagnosis
Charcot’s joints is suspected when a person with a
disease that impairs pain sensation exhibits painless
swelling and/or stiffness in a joint. Standard x rays will
show damage to the joint, and may also show abnormal bone growth and calcium deposits. Floating bone
fragments from previous injuries may also be visible.

Treatment
In the early stages of Charcot’s joints, braces to
stabilize the joints can help stop or minimize the
damage. When the disease has progressed beyond
braces, surgery can sometimes repair the joint. If the
damage is extensive, an artificial joint may be necessary.
816

I Chelation therapy
Definition
Chelation therapy is an intravenous treatment
designed to bind heavy metals in the body in order to
treat heavy metal toxicity. Proponents claim it also
treats coronary artery disease and other illnesses that
may be linked to damage from free radicals (reactive
molecules).

Purpose
The benefits of EDTA chelation for the treatment
of lead poisoning and excessively high calcium levels
are undisputed. The claims of benefits for those suffering from atherosclerosis, coronary artery disease, and
other degenerative diseases are more difficult to prove.
Reported uses for chelation therapy include treatment
of angina, gangrene, arthritis, multiple sclerosis,
Parkinson’s disease, psoriasis, and Alzheimer’s disease.
Improvement is also claimed for people experiencing
diminished sight, hearing, smell, coordination, and
sexual potency.

Description
Origins
The term chelation is from the Greek root word
‘‘chele,’’ meaning ‘‘claw.’’ Chelating agents, most
commonly diamine tetraacetic acid (EDTA), were
GALE ENCYCLOPEDIA OF MEDICINE

If the preparatory examination suggests that there
is a condition that could be improved by chelation
therapy, and there is no health reason why it shouldn’t
be used, then the treatment can begin. The patient is
generally taken to a comfortable treatment area,
sometimes in a group location, and an intravenous
line is started. A solution of EDTA together with
vitamins and minerals tailored for the individual
patient is given. Most treatments take three to four
hours, as the infusion must be given slowly in order to
be safe. The number of recommended treatments is
usually between 20 and 40. They are given one to three
times a week. Maintenance treatments can then be
given at the rate of once or twice a month. Maximum
benefits are reportedly attained after approximately
three months after a treatment series. The cost of
therapy is considerable, but it is a fraction of the cost
of an expensive medical procedure like cardiac bypass
surgery. Intravenous vitamin C and mercury chelation
therapies are also offered.

Preparations
A candidate for chelation therapy should initially
have a thorough history and physical to define the type
and extent of clinical problems. Laboratory tests will
be done to determine whether there are any conditions
present that would prevent the use of chelation.
Patients who have preexisting hypocalcemia, poor
liver or kidney function, congestive heart failure, hypoglycemia, tuberculosis, clotting problems, or potentially allergic conditions are at higher risk for
complications from chelation therapy. A Doppler
ultrasound may be performed to determine the adequacy of blood flow in different regions of the body.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Angina—Chest pain caused by reduced oxygen to
the heart.
Atherosclerosis—Arterial disease characterized by
fatty deposits on inner arterial walls.
Hypocalcemia—Low blood calcium.
Hypoglycemia—Low blood sugar.
Intermittent claudication—Leg pain and weakness
caused by walking.
Thrombophlebitis—Inflammation of a vein together
with clot formation.

Precautions
It is important for people who receive chelation
therapy to work with medical personnel who are
experienced in the use of this treatment. Treatment
should not be undertaken before a good physical, lifestyle evaluation, history, and any laboratory tests
necessary are performed. The staff must be forthcoming about test results and should answer any questions
the patient may have. Evaluation and treatment
should be individualized and involve assessment of
kidney function before each treatment with chelation,
since the metals bound by the EDTA are excreted
through the kidneys.
Although EDTA binds harmful, toxic metals like
mercury, lead, and cadmium, it also binds some essential nutrients of the body, such as copper, iron, calcium, zinc, and magnesium. Large amounts of zinc are
lost during chelation. Zinc deficiency can cause
impaired immune function and other harmful effects.
Supplements of zinc are generally given to patients
undergoing chelation, but it is not known whether
this is adequate to prevent deficiency. Also, chelation
therapy does not replace proper nutrition, exercise,
and appropriate medications or surgery for specific
diseases or conditions.

Side effects
Side effects of chelation therapy are reportedly
unusual, but are occasionally serious. Mild reactions
may include, but are not limited to, local irritation at
the infusion site, skin reactions, nausea, headache,
dizziness, hypoglycemia, fever, leg cramps, or loose
bowel movements. Some of the more serious complications reported have included hypocalcemia, kidney
damage, decreased clotting ability, anemia, bone
817

Chelation therapy

originally designed for industrial applications in the
early 1900s. It was not until the World War II era that
the potential for medical therapy was realized. The
initial intent was to develop antidotes to poison gas
and radioactive contaminants. The need for widespread
therapy of this nature did not materialize, but more
practical uses were found for chelation. During the
following decade, EDTA chelation therapy became
standard treatment for people suffering from lead poisoning. Patients who had received this treatment
claimed to have other health improvements that could
not be attributed to the lead removal only. Especially
notable were comments from those who had previously
suffered from intermittent claudication and angina.
They reported suffering less pain and fatigue, with
improved endurance, after chelation therapy. These
reports stimulated further interest in the potential benefits of chelation therapy for people suffering from
atherosclerosis and coronary artery disease.

Chemonucleolysis

marrow damage, insulin shock, thrombophlebitis with
embolism, and even rare deaths. However, some doctors feel that the latter groups of complications
occurred before the safer method currently used for
chelation therapy was developed.

Research and general acceptance
EDTA chelation is a highly controversial therapy.
The treatment is approved by the United States Food
and Drug Administration (FDA) for lead poisoning
and seriously high calcium levels. However, for the
treatment of atherosclerotic heart disease, EDTA
chelation therapy is not endorsed by the American
Heart Association (AHA), the FDA, the National
Institutes of Health (NIH), or the American College
of Cardiology. The AHA reports that there are no
adequate, controlled, published scientific studies
using currently approved scientific methods to support this therapy for the treatment of coronary artery
disease. However, a pooled analysis from the results of
over 70 studies showed positive results in all but one.
Resources
ORGANIZATIONS

The American College for Advancement in Medicine
(ACAM). 23121 Verdugo Dr., Suite 204, Laguna Hills,
CA 92653. (714) 583-7666.
American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-630 or (800) 242-8721. inquire
@heart.org. <http://www.americanheart.org>.
OTHER

Cranton, Elmer. Chelation therapy. 1999. <http://
www.drcranton.com/chelation.html>.
Green, Saul. Quackwatch: Chelation therapy. 2000. <http://
www.quackwatch.com/01QuackeryRelatedTopics/
chelation.html>.

Judith Turner

Chemica see Skin resurfacing

material in an intervertebral disk by the injection of
an enzyme such as chymopapain.

Purpose
Between each vertebra lies a disk of cushioning
material that keeps the spinal bones from rubbing
together and absorbs some of the shock to the spine
from body movements. In the center of the disk is soft,
gelatinous material called the nucleus pulposus (NP).
The NP is surrounded by a tough fibrous coating.
Sometimes when the back is injured, this coating can
weaken and bulge or tear to allow the NP to ooze out.
When this happens, it is called a herniated nucleus
pulposus (HNP), or–in common language–a herniated
disk.
When the disk bulges or herniates, it can put
pressure on nerves which originate in the spinal column, and go to other parts of the body. This causes
lower back pain, and/or pain to the hips, legs, arms,
shoulders, and neck, depending on the location of the
herniated disk. Chemonucleolysis uses chymopapain,
an enzyme derived from papyrus, to dissolve the disk
material that has been displaced because of injury.
Herniated disks are the cause of only a small proportion of cases of lower back pain, and chemonucleolysis
is appropriate for only some cases of HNP.
Chemonucleolysis is a conservative alternative to
disk surgery. There are three types of disk injuries.
A protruded disk is one that is intact but bulging. In
an extruded disk, the fibrous wrapper has torn and the
NP has oozed out, but is still connected to the disk. In
a sequestered disk, a fragment of the NP has broken
loose from the disk and is free in the spinal canal.
Chemonucleolysis is effective on protruded and
extruded disks, but not on sequestered disk injuries.
In the United States, chymopapain chemonucleolysis
is approved only for use in the lumbar (lower) spine. In
other countries, it has also been used successfully to
treat cervical (upper spine) hernias.

Chemical debridement see Debridement

Other indications that a patient is a good candidate for chemonucleolysis instead of surgery include:

Chemobrasion see Skin resurfacing



the patient is 18–50 years of age



leg pain is worse than lower back pain



other conservative treatments have failed



The spot where the herniated disk presses on the
nerve has been pinpointed by myelography, computed
tomography scan (CT scan), or magnetic resonance
imaging (MRI)



the patient wishes to avoid surgery

I Chemonucleolysis
Definition
Chemonucleolysis is a medical procedure that
involves the dissolving of the gelatinous cushioning
818

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Chymopapain—An enzyme from the milky white
fluid of the papaya, used for medical purposes in
chemonucleolysis.
Myelography—An x-ray test that evaluates the subarachnoid space of the spine.
Nucleus pulposus (NP)—an elastic, pulpy mass in
the center of each vertebral disk.

Precautions
There are some situations in which chemonucleolysis should not be performed. Chymopapain is
derived from the papaya. About 0.3% of patients are
allergic to chymopapain and go into life-threatening
shock when exposed to the enzyme. Chemonucleolysis
should not be performed on patients allergic to
chymopapain or papaya. It also should not be done:


when the patient is pregnant



if the disk is sequestered



if the patient has had several failed back operations



if a spinal cord tumor is present



if the patient has a neurological disease such as multiple sclerosis

Other conditions may affect the appropriateness
of chemonucleolysis, including hypertension, obesity,
diabetes, and a family history of stroke.

The greatest risk is that the patient may be allergic
to chymopapain. The death rate for chemonucleolysis
is only 0.02%. Complications overall are five to 10
times less than with conventional surgery, and the
failure rate is roughly comparable to the failure rate
in conventional disk surgery.

Normal results
Many patients feel immediate relief from pain,
but, in about 30% of patients, maximal relief takes
six weeks. The long term (seven to 20 years) success
rate averages about 75%, which is comparable to the
success rate for conventional surgery.
Resources
PERIODICALS

Alexander, Herbert. ‘‘Chemonucleolysis for Lumbar Disc
Herniation: How Does it Stack up to Other Minimally
Invasive Approaches?’’ Journal of Musculoskelatal
Medicine 12, no. 2 (1995): 13-24.

Tish Davidson, A.M.

I Chemotherapy
Definition
Chemotherapy is treatment of cancer with anticancer drugs.

Description
A small gauge needle is placed in the center of the
affected disk. Chymopapain is introduced into the
disk. The patient needs to remain still.

Preparation
Patients will need tests such as a myelogram or CT
scan to pinpoint the herniated disk. Some doctors
medicate the patient 24 hours prior to the operation
in order to decrease the chances of post-operative
lower back stiffness.

Aftercare
Patients may feel lower back stiffness, which goes
away in few weeks. Heavy lifting and sports activities
should be avoided for at least three months.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
The main purpose of chemotherapy is to kill cancer cells. It usually is used to treat patients with cancer
that has spread from the place in the body where it
started (metastasized). Chemotherapy destroys cancer
cells anywhere in the body. It even kills cells that have
broken off from the main tumor and traveled through
the blood or lymph systems to other parts of the body.
Chemotherapy can cure some types of cancer. In
some cases, it is used to slow the growth of cancer cells
or to keep the cancer from spreading to other parts of
the body. When a cancer has been removed by surgery,
chemotherapy may be used to keep the cancer from
coming back (adjuvant therapy). Chemotherapy also
can ease the symptoms of cancer, helping some
patients have a better quality of life.
819

Chemotherapy

Risks

Chemotherapy

Precautions
There are many different types of chemotherapy
drugs. Oncologists, doctors who specialize in treating
cancer, determine which drugs are best suited for each
patient. This decision is based on the type of cancer,
the patient’s age and health, and other drugs the
patient is taking. Some patients should not be treated
with certain chemotherapy drugs. Age and other conditions may affect the drugs with which a person may
be treated. Heart disease, kidney disease, and diabetes
are conditions that may limit the choice of treatment
drugs. In 2003, research revealed that obesity appears
to reduce the effectives of high-dose chemotherapy.
Researchers said further study was needed to determine the best dosage for obese patients receiving
therapy.

Description
More than 50 chemotherapy drugs are currently
available to treat cancer and many more are being
tested for their ability to destroy cancer cells. Most
chemotherapy drugs interfere with the ability of cells
to grow or multiply. Although these drugs affect all
cells in the body, many useful treatments are most
effective against rapidly growing cells. Cancer cells
grow more quickly than most other body cells. Other
cells that grow fast are cells of the bone marrow that
produce blood cells, cells in the stomach and intestines, and cells of the hair follicles. Therefore, the
most common side effects of chemotherapy are linked
to the treatment’s effects on other fast growing cells.
Types of chemotherapy drugs
Chemotherapy drugs are classified based on how
they work. The main types of chemotherapy drugs are
described below:


Alkylating drugs kill cancer cells by directly attacking DNA, the genetic material of the genes.
Cyclophosphamide is an alkylating drug.



Antimetabolites interfere with the production of DNA
and keep cells from growing and multiplying. An
example of an antimetabolite is 5-fluorouracil (5-FU).



Antitumor antibiotics are made from natural substances such as fungi in the soil. They interfere with
important cell functions, including production of
DNA and cell proteins. Doxorubicin and bleomycin
belong to this group of chemotherapy drugs.



Plant alkaloids prevent cells from dividing normally.
Vinblastine and vincristine are plant alkaloids
obtained from the periwinkle plant.

820



Steroid hormones slow the growth of some cancers
that depend on hormones. For example, tamoxifen is
used to treat breast cancers that depend on the hormone estrogen for growth.
Combination chemotherapy

Chemotherapy usually is given in addition to
other cancer treatments, such as surgery and radiation
therapy. When given with other treatments, it is called
adjuvant chemotherapy. An oncologist decides which
chemotherapy drug or combination of drugs will work
best for each patient. The use of two or more drugs
together often works better than a single drug for
treating cancer. This is called combination chemotherapy. Scientific studies of different drug combinations
help doctors learn which combinations work best for
each type of cancer. For example, new research in 2003
found that a combination of chemotherapy and gene
therapy stopped breast cancer and its metastasis
(spread to other organs or parts of the body).
How chemotherapy is given
Chemotherapy is administered in different ways,
depending on the drugs to be given and the type of
cancer. Doctors decide the dose of chemotherapy
drugs considering many factors, among them being
the patient’s height and weight.
Chemotherapy may be given by one or more of
the following methods:


orally



by injection



through a catheter or port



topically

Oral chemotherapy is given by mouth in the form
a pill, capsule, or liquid. This is the easiest method and
can usually be done at home.
Intravenous (IV) chemotherapy is injected into a
vein. A small needle is inserted into a vein on the hand
or lower arm. The needle usually is attached to a small
tube called a catheter, which delivers the drug to the
needle from an IV bag or bottle.
Intramuscular (IM) chemotherapy is injected into
a muscle. Chemotherapy given by intramuscular injection is absorbed into the blood more slowly than IV
chemotherapy. Because of this, the effects of IM chemotherapy may last longer than chemotherapy given
intravenously. Chemotherapy also may be injected subcutaneously (SQ or SC), which means under the skin.
Injection of chemotherapy directly into the cancer is
called intralesional (IL) injection.
GALE ENCYCLOPEDIA OF MEDICINE

Chemotherapy

Chemotherapy also may be given by a catheter or
port permanently inserted into a central vein or body
cavity. A port is a small reservoir or container that is
placed in a vein or under the skin in the area where the
drug will be given. These methods eliminate the need
for repeated injections and may allow patients to
spend less time in the hospital while receiving
chemotherapy. A common location for a permanent
catheter is the external jugular vein in the neck.
Intraperitoneal (IP) chemotherapy is administered
into the abdominal cavity through a catheter or port.
Chemotherapy given by catheter or port into the
spinal fluid is called intrathecal (IT) administration.
Catheters and ports also may be placed in the chest
cavity, bladder, or pelvis, depending on the location of
the cancer to be treated.
Topical chemotherapy is given as a cream or ointment applied directly to the cancer. This method is
more common in treatment of certain types of skin
cancer.
Treatment location and schedule
Patients may take chemotherapy at home, in the
doctor’s office, or as an inpatient or outpatient at the
hospital. Most patients stay in the hospital when first
beginning chemotherapy, so their doctor can check for
any side effects and change the dose if needed.
How often and how long chemotherapy is given
depends on the type of cancer, how patients respond to
the drugs, patients’ health and ability to tolerate the
drugs, and the types of drugs given. Chemotherapy
administration may take only a few minutes or may
last as long as several hours. Chemotherapy may be
given daily, weekly, or monthly. A rest period may
follow a course of treatment before the next course
begins. In combination chemotherapy, more than one
drug may be given at a time, or they may be given
alternately, one following the other.

Preparation
A number of medical tests are done before chemotherapy is started. The oncologist will determine how
much the cancer has spread from the results of x rays
and other imaging tests and from samples of the tumor
taken during surgery or biopsy.
Blood tests give the doctor important information
about the function of the blood cells and levels of
chemicals in the blood. A complete blood count
(CBC) is commonly done before and regularly during
treatment. The CBC shows the numbers of white
blood cells, red blood cells, and platelets in the
GALE ENCYCLOPEDIA OF MEDICINE

Patient undergoing high dose stem cell chemotherapy.
(Custom Medical Stock Photo. Reproduced by permission.)

blood. Because chemotherapy affects the bone marrow, where blood cells are made, levels of these cells
often drop during chemotherapy. The white blood
cells and platelets are most likely to be affected by
chemotherapy. A drop in the white blood cell count
means the immune system cannot function properly.
Low levels of platelets can cause a patient to bleed
easily from a cut or other wound. A low red blood
cell count can lead to anemia (deficiency of red blood
cells) and fatigue.
When a chemotherapy treatment takes a long
time, the patient may prepare for it by wearing comfortable clothes. Bringing a book to read or a tape to
listen to may help pass the time and ease the stress of
receiving chemotherapy. Some patients bring a friend
or family member to provide company and support
during treatment.
Sometimes, patients taking chemotherapy drugs
known to cause nausea are given medications called
821

Chemotherapy

anti-emetics before chemotherapy is administered.
Anti-emetic drugs help to lessen feelings of nausea.
Two anti-nausea medications that may be used are
Kytril and Zofran.



easy bleeding or bruising



sores in the mouth and throat



neuropathy and other damage to the nervous system

Other ways to prepare for chemotherapy and help
lessen nausea are:



kidney damage



regularly eating nutritious foods and drinking lots of
fluids



eating and drinking normally until about two hours
before chemotherapy



eating high carbohydrate, low-fat foods and avoiding spicy foods

New research also revealed in 2003 that taking
melatonin, a natural hormone substance, may help
improve chemotherapy’s effectiveness and reduce the
toxic effects of the drugs.

Aftercare
Tips for helping to control side effects after
chemotherapy include:


Following any instructions given by the doctor or
nurse



Taking all prescribed medications



Eating small amounts of bland foods



Drinking lots of fluids



Getting plenty of rest.

Some patients find it helps to breathe fresh air or
get mild exercise, such as taking a walk.

Risks
Chemotherapy drugs are toxic to normal cells as
well as cancer cells. A dose that will destroy cancer
cells will probably cause damage to some normal cells.
Doctors adjust doses to do the least amount of harm
possible to normal cells. Some patients feel few or no
side effects, and others may have more serious side
effects. In some cases, a dose adjustment is all that is
needed to reduce or stop a side effect.
Some chemotherapy drugs have more side effects
than others. Some of the most common side effects
are:


nausea and vomiting



loss of appetite



hair loss



anemia and fatigue



infection

822

Nausea and vomiting are common, but can usually
be controlled by taking antinausea drugs, drinking
enough fluids, and avoiding spicy foods. Loss of appetite may be due to nausea or the stress of undergoing
cancer treatment.
Some chemotherapy drugs cause hair loss, but it is
almost always temporary.
Low blood cell counts caused by the effect of
chemotherapy on the bone marrow can lead to anemia, infections, and easy bleeding and bruising.
Patients with anemia have too few red blood cells to
deliver oxygen and nutrients to the body’s tissues.
Anemic patients feel tired and weak. If red blood cell
levels fall too low, a blood transfusion may be given.
Patients receiving chemotherapy are more likely
to get infections. This happens because their infectionfighting white blood cells are reduced. It is important
to take measures to avoid getting infections. When the
white blood cell count drops too low, the doctor may
prescribe medications called colony stimulating factors that help white blood cells grow. Neupogen and
Leukine are two colony stimulants used as treatments
to help fight infection.
Platelets are blood cells that make the blood clot.
When patients do not have enough platelets, they may
bleed or bruise easily, even from small injuries.
Patients with low blood platelets should take precautions to avoid injuries. Medicines such as aspirin and
other pain relievers can affect platelets and slow down
the clotting process.
Chemotherapy can cause irritation and dryness in
the mouth and throat. Painful sores may form that can
bleed and become infected. Precautions to avoid this
side effect include getting dental care before chemotherapy begins, brushing the teeth and gums regularly
with a soft brush, and avoiding mouth washes that
contain salt or alcohol.

Normal results
The main goal of chemotherapy is to cure cancer.
Many cancers are cured by chemotherapy. It may be
used in combination with surgery to keep a cancer
from spreading to other parts of the body. Some widespread, fast-growing cancers are more difficult to
treat. In these cases, chemotherapy may slow the
growth of the cancer cells.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Adjuvant therapy—Treatment given after surgery
or radiation therapy to prevent the cancer from
coming back.
Alkaloid—A type of chemical commonly found in
plants and often having medicinal properties.

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Toni Rizzo
Teresa G. Odle

Alykylating drug—A drug that kills cells by directly
damaging DNA.
Antiemetic—A medicine that helps control nausea;
also called an anti-nausea drug.
Antimetabolite—A drug that interferes with a cell’s
growth or ability to multiply.
Platelets—Blood cells that function in blood clotting.

I Chest drainage therapy
Definition

Doctors can tell if the chemotherapy is working by
the results of medical tests. Physical examination,
blood tests, and x rays are all used to check the effects
of treatment on the cancer.
The possible outcomes of chemotherapy are:


Complete remission or response. The cancer completely disappears. The course of chemotherapy is completed and the patient is tested regularly for a
recurrence.



Partial remission or response. The cancer shrinks in
size but does not disappear. The same chemotherapy
may be continued or a different combination of
drugs may be tried.



Stabilization. The cancer does not grow or shrink.
Other therapy options may be explored. A tumor
may stay stabilized for many years.



Progression. The cancer continues to grow. Other
therapy options may be explored.



A secondary malignancy may develop from the one
being treated, and that second cancer may need additional chemotherapy or other treatment.

Resources
PERIODICALS

‘‘Gene Therapy and Chemotherapy Combine to Stop Breast
Cancer and its Metastasis.’’ Gene Therapy Weekly
October 30, 2003: 2.
‘‘Melatonin Improves the Efficacy of Chemotherapy and
Quality of Life.’’ Biotech Week September 10, 2003:
394.
‘‘Obesity May Reduce Efficacy of High-dose
Chemotherapy.’’Health & Medicine Week August 11,
2003: 385.
GALE ENCYCLOPEDIA OF MEDICINE

Chest drainage therapy involves the removal of
air, blood, pus, or other secretions from the chest
cavity.

Purpose
Chest drainage therapy is done to relieve pressure
on the lungs, and remove fluid that could promote
infection. Installing a chest drainage tube can be either
an emergency or a planned procedure.
Removing air or fluids from the chest involves the
insertion of a tube through the skin and the muscles
between the ribs, and into the chest cavity. This cavity
is also called the pleural space. Insertion of this tube is
called thoracostomy, and chest drainage therapy is
sometimes called thoracostomy tube drainage.
Conditions that may need to be treated by chest
drainage therapy include emphysema (air in the tissues
of the lungs), tuberculosis, and spontaneous pneumothorax (air in the chest cavity) that causes more than a
25% collapse of the lung. Other conditions include
cancer that causes excessive secretions, empyema (pus
in the thoracic cavity), or hemothorax (blood in the
thoracic cavity). Almost all chest drainage therapy is
done to drain blood from the chest cavity after lung or
heart surgery. In cases where the lung is collapsed,
removing fluids by chest drainage therapy allows the
lung to reinflate.
Oftentimes an x ray is performed prior to treatment to determine whether the problem is either fluid
or air in the pleural space. Sometimes a procedure
called thoracentesis is performed in an effort to avoid
inserting a chest drainage tube. In this procedure a
needle with a catheter is inserted into the pleural
space and fluid is removed. When fluid continues to
823

Chest drainage therapy

ORGANIZATIONS

Chest drainage therapy

accumulate, chest drainage therapy is usually the next
step. This is especially true when there is a lung infection underlying the fluid build-up.

KEY TERMS
Empyema—Pus in the pleural cavity.

Precautions
Chest drainage therapy is not done if a collapsed
lung is not life-threatening. It also should be avoided
for patients who have blood clotting problems.

Description
Most patients are awake when the chest drainage
tube is inserted. They are given a sedative and a local
anesthetic. Chest drainage tubes are usually inserted
between the ribs. The exact location depends on the
type of material to be drained and its location in the
lungs.
An incision is made in the skin and through the
muscles between the ribs. A chest tube is inserted and
secured in place. The doctor connects one end of the
tube to the chest drainage system.
The chest drainage system must remain sealed to
prevent air from entering the chest cavity through the
tube. One commonly used system is a water-seal drainage system, comprised of three compartments that
collect and drain the fluid or air without allowing air
to backflow into the tube. An alternative to this system
is to connect the tube to a negative suction pump.
Once the tube and drainage system are in place, a
chest x ray is done to confirm that the tube is in the
right location, and that it is working. In some cases it
may be necessary to insert more than one tube to drain
localized pockets of fluid that have accumulated.

Hemothorax—Blood in the pleural cavity.
Pleural cavity—The area of the chest that includes
the lining of the chest cavity, the space the lungs are
located in, and the membrane covering of the
lungs.
Spontaneous pneumothorax—Air in the chest cavity that occurs because of disease or other naturally
occurring cause. Air and blood together in this
space is called a pneumohemothorax.

leaking into the space. If the patient is on mechanical
ventilation, the tube is often left in place until a
respirator is no longer necessary. Chest drainage therapy is usually done in conjunction with treating the
underlying cause of the fluid build-up.
The fluid that has been drained is examined for
bacterial growth, cancer cells, pus, and blood – to
determine the underlying cause of the condition and
appropriate treatment.

Risks
Problems can arise in the insertion of the tube if
the membrane lining the chest cavity is thick or if it has
many adhesions. The tube will not drain correctly if the
chest cavity contains blood clots or thick secretions
that are often associated with infections. Excessive
bleeding may occur during the insertion and positioning of the tube. Infection may result from the procedure. Pain is also a common complication.

Preparation
A chest x ray is usually done before the chest
drainage tube is inserted. Sometimes fluid becomes
trapped in isolated spaces in the lung, and it is necessary to do an ultrasound to determine where to locate
the drainage tube. Computed tomography scans (CT)
are useful in locating small pockets of fluids caused by
cancer or tuberculosis.

Normal results
The gas, pus, or blood is drained from the chest
cavity, and the lungs reinflate or begin to function
more efficiently. The site at which the tube was
inserted heals normally.
Resources
BOOKS

Aftercare
Normally after the material has been removed
from the chest cavity and the situation is resolved,
the chest drainage tube is removed. In cases where
the reason for the tube was air in the pleural cavity,
the tube is clamped and left in place several hours
before it is removed to make sure no more air is
824

McPhee, Stephen, et al., editors. Current Medical Diagnosis
and Treatment, 1998. 37th ed. Stamford: Appleton &
Lange, 1997.

Tish Davidson, A.M.

Chest pain see Angina
GALE ENCYCLOPEDIA OF MEDICINE

recent heart attack



pulmonary embolism

Definition



lung abscess



active hemorrhage



some spine injuries



recent surgery, open wounds, or burns

Chest physical therapy is the term for a group of
treatments designed to improve respiratory efficiency,
promote expansion of the lungs, strengthen respiratory muscles, and eliminate secretions from the
respiratory system.

Purpose
The purpose of chest physical therapy, also called
chest physiotherapy, is to help patients breathe more
freely and to get more oxygen into the body. Chest
physical therapy includes postural drainage, chest percussion, chest vibration, turning, deep breathing exercises, and coughing. It is usually done in conjunction
with other treatments to rid the airways of secretions.
These other treatments include suctioning, nebulizer
treatments, and the administration of expectorant
drugs.
Chest physical therapy can be used with newborns, infants, children, and adults. People who benefit from chest physical therapy exhibit a wide range of
problems that make it difficult to clear secretions from
their lungs. Some people who may receive chest physical therapy include people with cystic fibrosis or
neuromuscular diseases like Guillain-Barré syndrome,
progressive muscle weakness (myasthenia gravis), or
tetanus. People with lung diseases such as bronchitis,
pneumonia, or chronic obstructive pulmonary disease
(COPD) also benefit from chest physical therapy.
People who are likely to aspirate their mucous secretions because of diseases such as cerebral palsy or
muscular dystrophy also receive chest physical therapy,
as do some people who are bedridden, confined to a
wheelchair, or who cannot breathe deeply because of
postoperative pain.

Precautions
Chest physical therapy should not be performed
on people with


bleeding from the lungs



neck or head injuries



fractured ribs



collapsed lungs



damaged chest walls



tuberculosis



acute asthma

GALE ENCYCLOPEDIA OF MEDICINE

Chest physical therapy

I Chest physical therapy



Description
Chest physical therapy can be performed in a
variety of settings including critical care units, hospitals, nursing homes, outpatient clinics, and at the
patient’s home. Depending on the circumstances,
chest physical therapy may be performed by anyone
from a respiratory care therapist to a trained member
of the patient’s family. Different patient conditions
warrant different levels of training.
Chest physical therapy consists of a variety of
procedures that are applied depending on the patient’s
health and condition. Hospitalized patients are reevaluated frequently to establish which procedures are
most effective and best tolerated. Patients receiving
long term chest physical therapy are reevaluated
about every three months.
Turning
Turning from side to side permits lung expansion.
Patients may turn themselves or be turned by a caregiver. The head of the bed is also elevated to promote
drainage if the patient can tolerate this position.
Critically ill patients and those dependent on mechanical respiration are turned once every one to two hours
around the clock.
Coughing
Coughing helps break up secretions in the lungs so
that the mucus can be suctioned out or expectorated.
Patients sit upright and inhale deeply through the
nose. They then exhale in short puffs or coughs.
Coughing is repeated several times a day.
Deep breathing
Deep breathing helps expand the lungs and forces
better distribution of the air into all sections of the
lung. The patient either sits in a chair or sits upright in
bed and inhales, pushing the abdomen out to force
maximum amounts of air into the lung. The abdomen
is then contracted, and the patient exhales. Deep
breathing exercises are done several times each day
for short periods.
825

Chest physical therapy

Postural drainage
Postural drainage uses the force of gravity to
assist in effectively draining secretions from the lungs
and into the central airway where they can either be
coughed up or suctioned out. The patient is placed in a
head or chest down position and is kept in this position
for up to 15 minutes. Critical care patients and those
depending on mechanical ventilation receive postural
drainage therapy four to six times daily. Percussion
and vibration may be performed in conjunction with
postural drainage.
Percussion
Percussion is rhythmically striking the chest wall
with cupped hands. It is also called cupping, clapping,
or tapotement. The purpose of percussion is to break
up thick secretions in the lungs so that they can be
more easily removed. Percussion is performed on each
lung segment for one to two minutes at a time.
Vibration
As with percussion, the purpose of vibration is to
help break up lung secretions. Vibration can be either
mechanical or manual. It is performed as the patient
breathes deeply. When done manually, the person performing the vibration places his or her hands against the
patient’s chest and creates vibrations by quickly contracting and relaxing arm and shoulder muscles while
the patient exhales. The procedure is repeated several
times each day for about five exhalations.

Preparation
The only preparation needed for chest physical
therapy is an evaluation of the patient’s condition
and determination of which chest physical therapy
techniques would be most beneficial.

Aftercare
Patients practice oral hygiene procedures to lessen
the bad taste or odor of the secretions they spit out.

Risks
Risks and complications associated with chest
physical therapy depend on the health of the patient.
Although chest physical therapy usually poses few
problems, in some patients it may cause


oxygen deficiency if the head is kept lowered for
drainage



increased intracranial pressure

826

KEY TERMS
Coughing—Coughing helps break up secretions in
the lungs so that the mucus can be suctioned out or
expectorated. Patients sit upright and inhale deeply
through the nose. They then exhale in short puffs or
coughs. Coughing is repeated several times per day.
Deep breathing—Deep breathing helps expand the
lungs and forces better distribution of the air into all
sections of the lung. The patient either sits in a chair
or sits upright in bed and inhales, pushing the abdomen out to force maximum amounts of air into the
lung. The abdomen is then contracted, and the
patient exhales. Deep breathing exercises are
done several times each day for short periods.
Percussion—This consists of rhythmically striking
the chest wall with cupped hands. It is also called
cupping, clapping, or tapotement. The purpose of
percussion is to break up thick secretions in the
lungs so that they can be more easily removed.
Percussion is performed on each lung segment for
one to two minutes at a time.
Postural drainage—This technique uses the force of
gravity to assist in effectively draining secretions
from the lungs and into the central airway where
they can either be coughed up or suctioned out. The
patient is placed in a head or chest down position
and is kept in this position for up to 15 minutes.
Critical care patients and those depending on
mechanical ventilation receive postural drainage
therapy four to six times daily. Percussion and vibration may be performed in conjunction with postural
drainage.
Turning—Turning from side to side permits lung
expansion. Patients may turn themselves or be
turned by a caregiver. The head of the bed is also
elevated to promote drainage if the patient can tolerate this position. Critically ill patients and those
dependent on mechanical respiration are turned
once every one to two hours around the clock.
Vibration—The purpose of vibration is to help
break up lung secretions. Vibration can be either
mechanical or manual. It is performed as the patient
breathes deeply. When done manually, the person
performing the vibration places his or her hands
against the patient’s chest and creates vibrations
by quickly contracting and relaxing arm and
shoulder muscles while the patient exhales. The
procedure is repeated several times each day for
about five exhalations.

GALE ENCYCLOPEDIA OF MEDICINE

temporary low blood pressure



bleeding in the lungs



pain or injury to the ribs, muscles, or spine



vomiting



inhaling secretions into the lungs



heart irregularities

most frequently performed x ray. In some cases,
chest x rays are ordered for a single check of an organ’s
condition, and at other times, serial x rays are ordered
to compare to previous studies. Some common reasons for chest x rays include:
Pulmonary disorders

Normal results
The patient is considered to be responding positively to chest physical therapy if some, but not necessarily all, of these changes occur:


increased volume of sputum secretions



changes in breath sounds



improved vital signs



improved chest x ray



increased oxygen in the blood as measured by arterial
blood gas values



patient reports of eased breathing

Resources
ORGANIZATIONS

Cystic Fibrosis Foundation. 6931 Arlington Road,
Bethesda, MD 20814. (800) 344-4823. <http://
www.cff.org>.

Tish Davidson, A.M.

Chest radiography see Chest x ray

I Chest x ray
Definition
A chest x ray is a procedure used to evaluate
organs and structures within the chest for symptoms
of disease. Chest x rays include views of the lungs,
heart, small portions of the gastrointestinal tract, thyroid gland and the bones of the chest area. X rays are a
form of radiation that can penetrate the body and
produce an image on an x–ray film. Another name
for x ray is radiograph.

Chest films are frequently ordered to diagnose or
rule out pneumonia. Other pulmonary disorders such
as emphysema or pneumothorax (presence of air or gas
in the chest cavity outside the lungs) may be detected
or evaluated through the use of chest x ray.
Cancer
A chest x ray may be ordered by a physician to
check for possible tumors of the lungs, thyroid, lymphoid tissue, or bones of the thorax. These may be
primary tumors. X rays also check for secondary
spread of cancer from one organ to another.
Cardiac disorders
While less sensitive than echocardiography, chest
x ray can be used to check for disorders such as congestive heart failure or pulmonary edema.
Other
Tuberculosis can be observed on chest x rays, as
can cardiac disease and damage to the ribs or lungs.
Chest x rays are used to see foreign bodies that may
have been swallowed or inhaled, and to evaluate
response to treatment for various diseases. Often the
chest x ray is also used to verify correct placement of
chest tubes or catheters.

Precautions
Pregnant women, particularly those in the first or
second trimester, should not have chest x rays unless
absolutely necessary. If the exam is ordered, women
who are, or could possibly be, pregnant must wear a
protective lead apron. Because the procedure involves
radiation, care should always be taken to avoid overexposure, particularly for children. However, the
amount of radiation from one chest x ray procedure
is minimal.

Description
Purpose
Chest x rays are ordered for a wide variety of
diagnostic purposes. In fact, this is probably the
GALE ENCYCLOPEDIA OF MEDICINE

Routine chest x rays consist of two views, the
frontal view (referred to as posterioranterior or PA)
and the lateral (side) view. It is preferred that the
827

Chest x ray



Chest x ray

Risks
The only risk associated with chest x ray is minimal
exposure to radiation, particularly for pregnant women
and children. Those patients should use protective lead
aprons during the procedure. Technologists are cautioned to carefully check possible dislodging of any
tubes or monitors in the chest area from the patient’s
placement during the exam.

Normal results
A radiologist, or physician specially trained in the
technique and interpretation of x rays, will evaluate
the results. A normal chest x ray will show normal
structures for the age and medical history or the
patient. Findings, whether normal or abnormal, will
be provided to the referring physician in the form of a
written report.

Abnormal results
A normal chest x ray of a child. (Photograph by Peter Berndt, M.D.,
P.A, Custom Medical Stock Photo. Reproduced by permission.)

patient stand for this exam, particularly when studying collection of fluid in the lungs.
During the actual time of exposure, the technologist will ask the patient to hold his or her breath. It is
very important in taking a chest x ray to ensure there is
no motion that could detract from the quality and
sharpness of the film image. The procedure will only
take a few minutes and the time patients must hold
their breaths is a matter of a few seconds.
The chest x ray may be performed in a physician’s
office or referred to an outpatient radiology facility or
hospital radiology department. In some cases, particularly for bedridden patients, a portable chest x ray may
be taken. Portable films are sometimes of poorer quality
than those taken with permanent equipment, but are the
best choice for some patients or situations. Bedridden
patients may be placed in as upright a position as possible to get a clear picture, particularly of chest fluid.

Preparation
There is no advance preparation necessary for
chest x rays. Once the patient arrives at the exam
area, a hospital gown will replace all clothing on the
upper body and all jewelry must be removed.

Aftercare
No aftercare is required by patients who have
chest x rays.
828

Abnormal findings on chest x rays are used in
conjunction with a physician’s physical exam findings,
patient medical history and other diagnostic tests to
reach a final diagnosis. For many diseases, chest x rays
are more effective when compared to previous chest
studies. The patient is asked to help the radiology
facility in locating previous chest radiographs from
other facilities.
Pulmonary disorders
Pneumonia shows up on radiographs as patches
and irregular areas of density (from fluid in the lungs).
If the bronchi, which are usually not visible, can
be seen, a diagnosis of bronchial pneumonia may
be made. Shifts or shadows in the hila (lung roots)
may indicate emphysema or a pulmonary abscess.
Widening of the spaces between ribs suggests emphysema. Other pulmonary diseases may also be detected
or suspected through chest x ray.
Cancer
In nearly all patients with lung cancer, some sort
of abnormality can be seen on a chest radiograph.
Hilar masses (enlargements at that part of the lungs
where vessels and nerves enter) are one of the more
common symptoms as are abnormal masses and fluid
buildup on the outside surface of the lungs or surrounding areas. Interstitial lung disease, which is a
large category of disorders, many of which are related
to exposure of substances (such as asbestos fibers),
may be detected on a chest x ray as fiberlike deposits,
often in the lower portions of the lungs.
GALE ENCYCLOPEDIA OF MEDICINE

Bronchi—Plural of bronchus. The air passages in
the lungs through which inhaled air passes on its
way to the lungs.
Diaphragm—The large muscle that is located
between the abdomen and the chest area. The diaphragm aids in breathing.
Gastrointestinal—The digestive organs and structures, including the stomach and intestines.
Interstitial lung disease—About 180 diseases fall
into this category of breathing disorders. Injury or
foreign substances in the lungs (such as asbestos
fibers) as well as infections, cancers, or inherited
disorders may cause the diseases. They can lead to
breathing or heart failure.
Lymphoid—Tissues relating to the lymphatic system. A thin, yellowish fluid, called lymph fluid,
travels throughout the body. The lymphatic system
helps control fluids in the body.
Portable chest x ray—An x ray procedure taken by
equipment that can be brought to the patient. The
resulting radiographs may not be as high in quality
as stationary x ray radiographs, but allow a technologist to come to the bedridden patient.
Pulmonary—Refers to the lungs and the breathing
system and function.
Serial x rays—A number of x rays performed at set
times in the disease progression or treatment intervals. The radiographs will be compared to one
another to track changes.
Sternum—Also referred to as the breast bone, this is
the long flat bone in the middle of the chest.
Thorax—The chest area, which runs between the
abdomen and neck and is encased in the ribs.
X ray—A form of electromagnetic radiation with
shorter wavelengths than normal light. X rays can
penetrate most structures.

Other
Congestive heart failure and other cardiac diseases may be indicated on the view of a heart and
lung in a chest radiograph. Fractures of the sternum
and ribs are usually easily detected as breaks on the
chest x ray. In some instances, the radiologist’s view of
the diaphragm may indicate an abdominal problem.
Tuberculosis can also be indicated by elevation of the
diaphragm. Foreign bodies which may have been
GALE ENCYCLOPEDIA OF MEDICINE

swallowed or inhaled can usually be located by the
radiologist as they will look different from any other
tissue or structure in the chest. Serial chest x rays may
be ordered to track changes over a period of time.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
Emphysema Anonymous, Inc. P.O. Box 3224, Seminole, FL
34642. (813)391-9977.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Teresa Odle

I Chickenpox
Definition
Chickenpox (also called varicella) is a common
and extremely infectious childhood disease that also
affects adults on occasion. It produces an itchy, blistery rash that typically lasts about a week and is sometimes accompanied by a fever or other symptoms.
A single attack of chickenpox almost always brings lifelong immunity against the disease. Because the symptoms of chickenpox are easily recognized and in most
cases merely unpleasant rather than dangerous, treatment can almost always be carried out at home. Severe
complications can develop, however, and professional
medical attention is essential in some circumstances.

Description
Before the varicella vaccine (Varivax) was
released for use in 1995, nearly all of the four million
children born each year in the United States contracted chickenpox, resulting in hospitalization in
five of every 1,000 cases and 100 deaths. Chickenpox
is caused by the varicella-zoster virus (a member of the
herpes virus family), which is spread through the air or
by direct contact with an infected person. Once someone has been infected with the virus, an incubation
period of about 10–21 days passes before symptoms
begin. The period during which infected people are
able to spread the disease is believed to start one or
two days before the rash breaks out and to continue
until all the blisters have formed scabs, which usually
829

Chickenpox

KEY TERMS

Chickenpox

happens four to 7 days after the rash breaks out but
may be longer in adolescents and adults. For this
reason, doctors recommend keeping children with
chickenpox away from school for about a week. It is
not necessary, however, to wait until all the scabs have
fallen off.
Chickenpox has been a typical part of growing up
for most children in the industrialized world (although
this may change if the new varicella vaccine becomes
more widely accepted). The disease can strike at any
age, but by ages nine or 10 about 80–90% of American
children have already been infected. U.S. children living in rural areas and many foreign-born children are
less likely to be immune. Because almost every case of
chickenpox, no matter how mild, leads to lifelong
protection against further attacks, adults account for
less than 5% of all cases in the United States. Study
results reported by the Centers for Disease Control
and Prevention (CDC) indicate that more than 90% of
American adults are immune to the chickenpox virus.
Adults, however, are much more likely than children
to suffer dangerous complications. More than half of
all chickenpox deaths occur among adults.

Causes and symptoms
A case of chickenpox usually starts without warning or with only a mild fever and a slight feeling of
unwellness. Within a few hours or days small red spots
begin to appear on the scalp, neck, or upper half of the
trunk. After a further 12–24 hours the spots typically
become itchy, fluid-filled bumps called vesicles, which
continue to appear in crops for the next two to five
days. In any area of skin, lesions of a variety of stages
can be seen. These blisters can spread to cover much of
the skin, and in some cases also may be found inside
the mouth, nose, ears, vagina, or rectum. Some people
develop only a few blisters, but in most cases the
number reaches 250–500. The blisters soon begin to
form scabs and fall off. Scarring usually does not
occur unless the blisters have been scratched and
become infected. Occasionally a minor and temporary
darkening of the skin (called hyperpigmentation) is
noticed around some of the blisters. The degree of
itchiness can range from barely noticeable to extreme.
Some chickenpox sufferers also have headaches,
abdominal pain, or a fever. Full recovery usually
takes five to 10 days after the first symptoms appear.
Again, the most severe cases of the disease tend to be
found among older children and adults.
Although for most people chickenpox is no more
than a matter of a few days’ discomfort, some groups
are at risk for developing complications, the most
830

common of which are bacterial infections of the blisters, pneumonia, dehydration, encephalitis, and
hepatitis:


Infants. Complications occur much more often
among children less than one year old than among
older children. The threat is greatest to newborns,
who are more at risk of death from chickenpox than
any other group. Under certain circumstances, children born to mothers who contract chickenpox just
prior to delivery face an increased possibility of dangerous consequences, including brain damage and
death. If the infection occurs during early pregnancy,
there is a small (less than 5%) risk of congenital
abnormalities.



Immunocompromised children. Children whose
immune systems have been weakened by a genetic
disorder, disease, or medical treatment usually
experience the most severe symptoms of any group.
They have the second-highest rate of death from
chickenpox.



Adults and children 15 and older. Among this group,
the typical symptoms of chickenpox tend to strike
with greater force, and the risk of complications is
much higher than among young children.

Immediate medical help should always be sought
when anyone in these high-risk groups contracts the
disease.

Diagnosis
Where children are concerned, especially those
with recent exposure to the disease, diagnosis can
usually be made at home, by a school nurse, or by a
doctor over the telephone if the child’s parent or caregiver is unsure that the disease is chickenpox.
A doctor should be called immediately if:


The child’s fever goes above 102  F (38.9  C) or takes
more than four days to disappear.



The child’s blisters appear infected. Signs of infection
include leakage of pus from the blisters or excessive
redness, warmth, tenderness, or swelling around the
blisters.



The child seems nervous, confused, unresponsive, or
unusually sleepy; complains of a stiff neck or severe
headache; shows signs of poor balance or has trouble
walking; finds bright lights hard to look at; is having
breathing problems or is coughing a lot; is complaining of chest pain; is vomiting repeatedly; or is having
convulsions. These may be signs of Reye’s syndrome
or encephalitis, two rare but potentially dangerous
conditions.
GALE ENCYCLOPEDIA OF MEDICINE

Chickenpox

Treatment
With children, treatment usually takes place in the
home and focuses on reducing discomfort and fever.
Because chickenpox is a viral disease, antibiotics are
ineffective against it.
Applying wet compresses or bathing the child in
cool or lukewarm water once a day can help the itch.
Adding four to eight ounces of baking soda or one or
two cups of oatmeal to the bath is a good idea (oatmeal bath packets are sold by pharmacies). Only mild
soap should be used in the bath. Patting, not rubbing,
is recommended for drying the child off, to prevent
irritating the blisters. Calamine lotion (and some other
kinds of lotions) also help to reduce itchiness. Because
scratching can cause blisters to become infected and
lead to scarring, the child’s nails should be cut short.
Of course, older children need to be warned not to
scratch. For babies, light mittens or socks on the
hands can help guard against scratching.
If mouth blisters make eating or drinking an
unpleasant experience, cold drinks and soft, bland
foods can ease the child’s discomfort. Painful genital
blisters can be treated with an anesthetic cream recommended by a doctor or pharmacist. Antibiotics often
are prescribed if blisters become infected.
Fever and discomfort can be reduced by acetaminophen or another medication that does not contain
aspirin. Aspirin and any medications that contain
aspirin or other salicylates must not be used with
chickenpox, for they appear to increase the chances
of developing Reye’s syndrome. The best idea is to
consult a doctor or pharmacist if unsure about which
medications are safe.

A five-year-old girl with chickenpox. The first symptom of the
disease is the rash that is evident on the girl’s back and neck.
The rash and the mild fever that accompanies it should disappear in a week or two. (Photograph by Jim Selby, Photo
Researchers, Inc. Reproduced by permission.)

Immunocompromised chickenpox sufferers are
sometimes given an antiviral drug called acyclovir
(Zovirax). Studies have shown that Zovirax also lessens the symptoms of otherwise healthy children and
adults who contract chickenpox, but the suggestion
that it should be used to treat the disease among
the general population, especially in children, is
controversial.

herbal preparations of rosemary (Rosmarinus officinalis) and calendula (Calendual officinalis) to the blisters.
Homeopathic remedies are selected on a case by case
basis. Some common remedy choices are tartar emetic
(antimonium tartaricum), windflower (pulsatilla), poison ivy (Rhus toxicodendron), and sulphur.

Alternative treatment
Alternative practitioners seek to lessen the discomfort and fever caused by chickenpox. Like other
practitioners, they suggest cool or lukewarm baths.
Rolled oats (Avena sativa) in the bath water help
relieve itching. (Oats should be placed in a sock, that
is turned in the bath water to release the milky antiitch properties.) Other recommended remedies for
itching include applying aloe vera, witch hazel, or
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Most cases of chickenpox run their course within
a week without causing lasting harm. However, there
is one long-term consequence of chickenpox that
strikes about 20% of the population, particularly people 50 and older. Like all herpes viruses, the varicellazoster virus never leaves the body after an episode
of chickenpox, but lies dormant in the nerve cells,
where it may be reactivated years later by disease or
831

Chickenpox

age-related weakening of the immune system. The
result is shingles (also called herpes zoster), a painful
nerve inflammation, accompanied by a rash, that
usually affects the trunk or the face for 10 days or
more. Especially in the elderly, pain, called postherpetic neuralgia, may persist at the site of the shingles for
months or years. Two relatively newer drugs for treatment of shingles have become available. Both valacyclovir (Valtrex) and famciclovir (Famvir) stop the
replication of herpes zoster when administered within
72 hours of appearance of the rash. The effectiveness
of these two drugs in immunocompromised patients
has not been established, and Famvir was not recommended for patients under 18 years.

Prevention
A substance known as varicella-zoster immune
globulin (VZIG), which reduces the severity of
chickenpox symptoms, is available to treat immunocompromised children and others at high risk of developing complications. It is administered by injection
within 96 hours of known or suspected exposure to
the disease and is not useful after that. VZIG is produced as a gamma globulin from blood of recently
infected individuals.
A vaccine for chickenpox became available in the
United States in 1995 under the name Varivax. Varivax
is a live, attenuated (weakened) virus vaccine. It has
been proven to be 85% effective for preventing all cases
of chickenpox and close to 100% effective in preventing
severe cases. Side effects are normally limited to occasional soreness or redness at the injection site. CDC
guidelines state that the vaccine should be given to all
children (with the exception of certain high-risk groups)
at 12–18 months of age, preferably when they receive
their measles-mumps-rubella vaccine. For older children, up to age 12, the CDC recommends vaccination
when a reliable determination that the child in question
has already had chickenpox cannot be made.
Vaccination also is recommended for any older child
or adult considered susceptible to the disease, particularly those, such as health care workers and women of
childbearing age, who face a greater likelihood of severe
illness or transmitting infection. A single dose of the
vaccine was once thought sufficient for children up to
age 12; older children and adults received a second dose
four to eight weeks later. However, an outbreak at a
daycare center in 2000 brought concern in the medical
community about a second vaccination for younger
children, since many of the affected children had been
vaccinated. Researchers began recommending a second
vaccination in 2002. In 1997 the cost of two adult doses
832

KEY TERMS
Acetaminophen—A drug for relieving pain and
fever. Tylenol is the most common example.
Acyclovir—An antiviral drug used for combating
chickenpox and other herpes viruses. Sold under
the name Zovirax.
Dehydration—Excessive water loss by the body.
Encephalitis—A disease that inflames the brain.
Hepatitis—A disease that inflames the liver.
Immune system—A biochemical complex that protects the body against pathogenic organisms and
other foreign bodies.
Immunocompromised—Havingadamagedimmune
system.
Pneumonia—A disease that inflames the lungs.
Pus—A thick yellowish or greenish fluid containing
inflammatory cells. Usually caused by bacterial
infection.
Reye’s syndrome—A rare but often fatal disease
that involves the brain, liver, and kidneys.
Salicylates—Substances containing salicylic acid,
which are used for relieving pain and fever. Aspirin
is the most common example.
Shingles—A disease (also called herpes zoster) that
causes a rash and a very painful nerve inflammation. An attack of chickenpox will eventually give
rise to shingles in about 20% of the population.
Trunk—That part of the body that does not include
the head, arms, and legs.
Varicella-zoster immune globulin (VZIG)—A substance that can reduce the severity of chickenpox
symptoms.
Varicella-zoster virus—The virus that causes
chickenpox and shingles.
Varivax—A vaccine for the prevention of chickenpox.
Virus—A tiny particle that can cause infections by
duplicating itself inside a cell using the cell’s own
software. Antibiotics are ineffective against viruses,
though antiviral drugs exist for some viruses,
including chickenpox.

of the vaccine in the United States was about $80.
Although this cost was not always covered by health
insurance plans, children up to age 18 without access to
the appropriate coverage could be vaccinated free of
charge through the federal Vaccines for Children
GALE ENCYCLOPEDIA OF MEDICINE

The vaccine also is not recommended for pregnant
women, and women should delay pregnancy for three
months following a complete vaccination. The vaccine
is useful when given early after exposure to chickenpox and, if given in the midst of the incubation period,
it can be preventative. The Infectious Diseases Society
of America stated in 2000 that immunization is recommended for all adults who have never had chickenpox.
While there was initial concern regarding the vaccine’s safety and effectiveness when first released, the
vaccination is gaining acceptance as numerous states
require it for admittance into daycare or public school.
In 2000, 59% of toddlers in the United States were
immunized; up from 43.2% in 1998. A study published
in 2001 indicates that the varicella vaccine is highly
effective when used in clinical practice. Although evidence has not ruled out a booster shot later in life, all
research addressing the vaccine’s effectiveness throughout its six-year use indicates that chickenpox may be the
first human herpes virus to be wiped out. Although initial
concerns questioned if the vaccination might make shingles more likely, studies are beginning to show the effectiveness of the vaccine in reducing cases of that disease.
Resources
PERIODICALS

Arvin, Ann M. ‘‘Varicella Vaccine–The First Six Years.’’
New England Journal of Medicine March 2001.
‘‘Chickenpox Vaccine OK for Pediatric Patients.’’ Vaccine
Weekly January 22, 2003: 25.
Henderson, C. W. ‘‘Chickenpox Immunization Confirmed
Effective in Adults.’’ Vaccine Weekly September 2000:
22.
‘‘Study: Two Vaccines Work Best.’’ Vaccine Weekly
January 8, 2003: 14.
ORGANIZATIONS

Centers for Disease Control and Prevention. National
Immunization Hotline. 1600 Clifton Rd. NE, Atlanta,
GA 30333. (800) 232-2522 (English). (800) 232-0233
(Spanish). <http://www.cdc.gov>.
OTHER

ABCNEWS.com. ‘‘Varicella Vaccine: States Mandate
Chickenpox Immunization.’’ August 1, 2000. [cited
May 3, 2001]. <http://abcnews.go.com/sections/living/
DailyNews/chickenpox_vaccine0802.html>.
Centers for Disease Control and Prevention. ‘‘Prevention of
Varicella: Recommendations of the Advisory
GALE ENCYCLOPEDIA OF MEDICINE

Committee on Immunization Practices (ACIP).’’ July
12, 1996. [cited December 12, 1997]. <http://aepo-xdvwww.epo.cdc.gov/wonder/prevguid/m0042990/
entire.htm>.

Beth A. Kapes
Teresa G. Odle

I Child abuse
Definition
Child abuse is the blanket term to describe four
types of child mistreatment: physical abuse, sexual
abuse, emotional abuse, and neglect. In many cases
children are the victims of more than one type of
abuse. The abusers can be parents or other family
members, caretakers such as teachers and babysitters,
acquaintances (including other children), and (in rare
instances) strangers.

Description
Prevalence of abuse
Child abuse was once viewed as a minor social
problem affecting only a handful of United States
children. However, it has begun to closer attention
from the media, law enforcement, and the helping
professions. With increased public and professional
awareness has come a sharp rise in the number of
reported cases. But because abuse often is hidden
from view and its victims too young or fearful to
speak out, experts suggest that its true prevalence is
possibly much greater than the official data indicate.
In 1996, more than three million victims of alleged
abuse were reported to child protective services
(CPS) agencies in the United States, and the reports
were substantiated in more than one million cases. Put
another way, 1.5% of the country’s children were
confirmed victims of abuse in 1996. Parents were the
abusers in 77% of the confirmed cases, other relatives
in 11%. Sexual abuse was more likely to be committed
by males, whereas females were responsible for the
majority of neglect cases. More than 1,000 United
States children died from abuse in 1996. A 2004 report
said that nearly 17% of adult women and 8% of adult
men had been abused as children. The United Nations
Children’s Fund (UNICEF) reported in early 2004
that nearly 3,500 children younger than age 15 die
every year from physical abuse and neglect in the 27
richest nations in the world.
833

Child abuse

program. Varivax is not given to patients who already
have overt signs of the disease. It was once thought
unsafe for children with chronic kidney disease, but a
2003 report said the vaccination was safe in these children. The finding is important, since even chickenpox
can be a serious complication in children who must
undergo a kidney transplant.

Child abuse

Although experts are quick to point out that abuse
occurs among all social, ethnic, and income groups,
reported cases usually involve poor families with little
education. Young mothers, single-parent families, and
parental alcohol or drug abuse also are common in
reported cases. Charles F. Johnson remarks, ‘‘More
than 90% of abusing parents have neither psychotic
nor criminal personalities. Rather they tend to be
lonely, unhappy, angry, young, and single parents
who do not plan their pregnancies, have little or no
knowledge of child development, and have unrealistic
expectations for child behavior.’’ About 10%, or perhaps as many as 40%, of abusive parents were themselves physically abused as children, but most abused
children do not grow up to be abusive parents.
Types of abuse
PHYSICAL ABUSE. Physical abuse is the nonacciden-

tal infliction of physical injury to a child. The abuser is
usually a family member or other caretaker, and is more
likely to be male. In 1996, 24% of the confirmed cases
of United States child abuse involved physical abuse.
A rare form of physical abuse is Munchausen syndrome by proxy, in which a caretaker (most often the
mother) seeks attention by making the child sick or
appear to be sick.
SEXUAL ABUSE. Charles F. Johnson defines child
sexual abuse as ‘‘any activity with a child, before the
age of legal consent, that is for the sexual gratification of
an adult or a significantly older child.’’ It includes,
among other things, sexual touching and penetration,
persuading a child to expose his or her sexual organs,
and allowing a child to view pornography. In most cases
the child is related to or knows the abuser, and about
one in five abusers are themselves underage. Sexual
abuse was present in 12% of the confirmed 1996 abuse
cases. An estimated 20–25% of females and 10–15% of
males report that they were sexually abused by age 18.

involving rejection, scapegoating, belittlement, and so
forth. Because it often accompanies other types of
abuse and is difficult to prove, it is rarely reported, and
accounted for only 6% of the confirmed 1996 cases.
NEGLECT. Neglect—failure to satisfy a child’s basic
needs—can assume many forms. Physical neglect is the
failure (beyond the constraints imposed by poverty) to
provide adequate food, clothing, shelter, or supervision. Emotional neglect is the failure to satisfy a child’s
normal emotional needs, or behavior that damages a
child’s normal emotional and psychological development (such as permitting drug abuse in the home).
Failing to see that a child receives proper schooling or
medical care is also considered neglect. In 1996 neglect
was the finding in 52% of the confirmed abuse cases.

Causes and symptoms
Physical abuse
The usual physical abuse scenario involves a parent who loses control and lashes out at a child. The
trigger may be normal child behavior such as crying or
dirtying a diaper. Unlike nonabusive parents, who
may become angry at or upset with their children
from time to time but are genuinely loving, abusive
parents tend to harbor deep-rooted negative feelings
toward their children.
Unexplained or suspicious bruises or other marks
on the skin are typical signs of physical abuse, as are
burns. Skull and other bone fractures are often seen in
young abused children, and in fact, head injuries are the
leading cause of death from abuse. Children less than
one year old are particularly vulnerable to injury from
shaking. This is called shaken baby syndrome or shaken
impact syndrome. Not surprisingly, physical abuse also
causes a wide variety of behavioral changes in children.
Sexual abuse

The 1990s and early 2000s were rocked by reports
of sexual abuse of children committed by Catholic
priests. Most of the abuse appeared to have occurred
during the 1970s and a prominent report released early
in 2004 stated that as many as 10,667 children were
sexually abused by more than 4,300 priests. Increases
also have been seen in recent years in child pornography cases, where children are the subjects of pornography, particularly on the Internet.

John M. Leventhal observes, ‘‘The two prerequisites for this form of maltreatment include sexual arousal to children and the willingness to act on this arousal.
Factors that may contribute to this willingness include
alcohol or drug abuse, poor impulse control, and a belief
that the sexual behaviors are acceptable and not harmful to the child.’’ The chances of abuse are higher if the
child is developmentally handicapped or vulnerable in
some other way.

EMOTIONAL ABUSE. Emotional abuse, according to
Richard D. Krugman, ‘‘has been defined as the rejection,
ignoring, criticizing, isolation, or terrorizing of children,
all of which have the effect of eroding their self-esteem.’’
Emotional abuse usually expresses itself in verbal attacks

Genital or anal injuries or abnormalities (including
the presence of sexually transmitted diseases) can be
signs of sexual abuse, but often there is no physical
evidence for a doctor to find. In fact, physical examinations of children in cases of suspected sexual abuse

834

GALE ENCYCLOPEDIA OF MEDICINE

Although these signs do not necessarily indicate that a child has been abused, they may help adults recognize that something is wrong. The possiblity of abuse should
be investigated if a child shows a number of these symptoms, or any of them to a marked degree:
Sexual Abuse
Being overly affectionate or knowledgeable in a sexual way inappropriate to the child’s age
Medical problems such as chronic itching, pain in the genitals, venereal diseases
Other extreme reactions, such as depression, self-mutilation, suicide attempts, running away, overdoses, anorexia
Personality changes such as becoming insecure or clinging
Regressing to younger behavior patterns such as thumb sucking or bringing out discarded cuddly toys
Sudden loss of appetite or compulsive eating
Being isolated or withdrawn
Inability to concentrate
Lack of trust or fear someone they know well, such as not wanting to be alone with a babysitter
Starting to wet bed again, day or night/nightmares
Become worried about clothing being removed
Suddenly drawing sexually explicit pictures
Trying to be ‘‘ultra-good’’ or perfect; overreacting to criticism
Physical Abuse
Unexplained recurrent injuries or burns
Improbable excuses or refusal to explain injuries
Wearing clothes to cover injuries, even in hot weather
Refusal to undress for gym
Bald patches
Chronic running away
Fear of medical help or examination
Self-destructive tendencies
Aggression towards others
Fear of physical contact—shrinking back if touched
Admitting that they are punished, but the punishment is excessive (such as a child being beaten every night to ‘‘make him/her study’’)
Fear of suspected abuser being contacted
Emotional Abuse
Physical, mental, and emotional development lags
Sudden speech disorders
Continual self-depreciation (‘‘I’m stupid, ugly, worthless, etc.’’)
Overreaction to mistakes
Extreme fear of any new situation
Inappropriate response to pain (‘‘I deserve this’’)
Neurotic behavior (rocking, hair twisting, self-mutilation)
Extremes of passivity or aggression
Neglect
Constant hunger
Poor personal hygiene
No social relationships
Constant tiredness
Poor state of clothing
Compulsive scavenging Emaciation
Untreated medical problems
Destructive tendencies
A child may be subjected to a combination of different kinds of abuse. It is also possible that a child may show no outward signs and hide what is happening from everyone.

supply grounds for further suspicion only 15–20% of
the time. Anxiety, poor academic performance, and
suicidal conduct are some of the behavioral signs of
sexual abuse, but are also found in children suffering
other kinds of stress. Excessive masturbation and other
unusually sexualized kinds of behavior are more closely
associated with sexual abuse itself.
Emotional abuse
Emotional abuse can happen in many settings: at
home, at school, on sports teams, and so on. Some of

GALE ENCYCLOPEDIA OF MEDICINE

the possible symptoms include loss of self-esteem,
sleep disturbances, headaches or stomach aches,
school avoidance, and running away from home.
Neglect
Many cases of neglect occur because the parent
experiences strong negative feelings toward the child.
At other times, the parent may truly care about the
child, but lack the ability or strength to adequately
provide for the child’s needs because he or she is
handicapped by depression, drug abuse, mental retardation, or some other problem.
835

Child abuse

Child Abuse: Signs And Symptoms

Child abuse

Neglected children often do not receive adequate
nourishment or emotional and mental stimulation.
As a result, their physical, social, emotional, and
mental development is hindered. They may, for
instance, be underweight, develop language skills less
quickly than other children, and seem emotionally
needy.

Diagnosis
Doctors and many other professionals who work
with children are required by law to report suspected
abuse to their state’s Child Protective Services (CPS)
agency. Abuse investigations often are a group effort
involving medical personnel, social workers, police officers, and others. Some hospitals and communities maintain child protection teams that respond to cases of
possible abuse. Careful questioning of the parents is
crucial, as is interviewing the child (if he or she is capable
of being interviewed). The investigators must ensure,
however, that their questioning does not further traumatize the child. A physical examination for signs of
abuse or neglect is, of course, always necessary, and
may include x rays, blood tests, and other procedures.

Treatment
Notification of the appropriate authorities, treatment of the child’s injuries, and protecting the child
from further harm are the immediate priorities in
abuse cases. If the child does not require hospital
treatment, protection often involves placing him or
her with relatives or in foster care. Once the immediate
concerns are dealt with, it becomes essential to determine how the child’s long-term medical, psychological, educational, and other needs can best be met, a
process that involves evaluating not only the child’s
needs but also the family’s (such as for drug abuse
counseling or parental skills training). If the child has
brothers or sisters, the authorities must determine
whether they have been abused as well. On investigation, signs of physical abuse are discovered in about
20% of the brothers and sisters of abused children.

Prognosis
Child abuse can have lifelong consequences.
Research shows that abused children and adolescents
are more likely, for instance, to do poorly in school,
suffer emotional problems, develop an antisocial personality, become promiscuous, abuse drugs and alcohol, and attempt suicide. As adults they often have
trouble establishing intimate relationships. Whether
professional treatment is able to moderate the long836

term psychological effects of abuse is a question that
remains unanswered.

Prevention
Government efforts to prevent abuse include
home-visitor programs aimed at high-risk families
and school-based efforts to teach children how
to respond to attempted sexual abuse. Emotional
abuse prevention has been promoted through the
media.
When children reach age three, parents should
begin teaching them about ‘‘bad touches’’ and about
confiding in a suitable adult if they are touched or
treated in a way that makes them uneasy. Parents also
need to exercise caution in hiring babysitters and
other caretakers. Anyone who suspects abuse should
immediately report those suspicions to the police or
his or her local CPS agency, which will usually be
listed in the blue pages of the telephone book under
Rehabilitative Services or Child and Family Services,
or in the yellow pages. Round-the-clock crisis counseling for children and adults is offered by the
Childhelp USA/IOF Foresters National Child
Abuse Hotline. The National Committee to Prevent
Child Abuse is an excellent source of information on
the many support groups and other organizations
that help abused and at-risk children and their
families. One of these organizations, National
Parents Anonymous, sponsors 2,100 local self-help
groups throughout the United States, Canada, and
Europe. Telephone numbers for its local groups are
listed in the white pages of the telephone book under
Parents Anonymous or can be obtained by calling the
national headquarters.
Resources
PERIODICALS

Jellinek, Michael S. ‘‘Making the Call: Identifying Child
Sexual Abuse.’’ Pediatric News March 2004: 26.
Plante, Thomas G. ‘‘Another Aftershock: What Have We
Learned from the John Jay Report?’’ America March
22, 2004: 10.
‘‘UNICEF Report on Child Abuse in Developed
Nations.’’ Public Health Reports March–April 2004:
220–224.
ORGANIZATIONS

Childhelp USA/IOF Foresters National Child Abuse
Hotline. (800) 422-4453.
National Clearinghouse on Child Abuse and Neglect
Information. P.O. Box 1182, Washington, DC 200131182. (800) 394-3366. <http://www.calib.com/
nccanch>.

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Childbirth

National Committee to Prevent Child Abuse. 200
S. Michigan Ave., 17th Floor, Chicago, IL 60604. (312)
663-3520. <http://www.childabuse.org>.
National Parents Anonymous. 675 W. Foothill Blvd., Suite
220, Claremont, CA 91711. (909) 621-6184.

Placenta
Umbilical cord
Uterus

Howard Baker
Teresa G. Odle
Vagina
Cervix

Child development see Children’s health
Child safety see Children’s health
Stage 1: Dilation of the cervix

I Childbirth

Stage 1: Dilation of the cervix. (Illustration by Hans & Cassady.)

Definition
Childbirth includes both labor (the process of
birth) and delivery (the birth itself); it refers to the
entire process as an infant makes its way from the
womb down the birth canal to the outside world.

Description
Childbirth usually begins spontaneously, about
280 days after conception, but it may be started
by artificial means if the pregnancy continues past
42 weeks gestation. The average length of labor is
about 14 hours for a first pregnancy and about eight
hours in subsequent pregnancies. However, many
women experience a much longer or shorter labor.
Labor can be described in terms of a series of
phases.
First stage of labor
During the first phase of labor, the cervix dilates
(opens) from 0–10 cm. This phase has an early, or
latent, phase and an active phase. During the latent
phase, progress is usually very slow. It may take quite
a while and many contractions before the cervix
dilates the first few centimeters. Contractions increase
in strength as labor progresses. Most women are relatively comfortable during the latent phase and walking
around is encouraged, since it naturally stimulates the
process.
As labor begins, the muscular wall of the uterus
begins to contract as the cervix relaxes and expands. As
a portion of the amniotic sac surrounding the baby is
pushed into the opening, it bursts under the pressure,
releasing amniotic fluid. This is called ‘‘breaking the
bag of waters.’’
GALE ENCYCLOPEDIA OF MEDICINE

During a contraction, the infant experiences
intense pressure that pushes it against the cervix, eventually forcing the cervix to stretch open. At the same
time, the contractions cause the cervix to thin. During
this first stage, a woman’s contractions occur more
and more often and last longer and longer. The doctor
or nurse will do a periodic pelvic exam to determine
how the mother is progressing. If the contractions
aren’t forceful enough to open the cervix, a drug may
be given to make the uterus contract.
As pain and discomfort increase, women may be
tempted to request pain medication. If possible,
though, administration of pain medication or anesthetics should be delayed until the active phase of
labor begins—at which point the medication will not
act to slow down or stop the labor.
The active stage of labor is faster and more efficient than the latent phase. In this phase, contractions
are longer and more regular, usually occurring about
every two minutes. These stronger contractions are
also more painful. Women who use the breathing
exercises learned in childbirth classes find that these
can help cope with the pain experienced during this
phase. Many women also receive some pain medication at this point—either a short-term medication,
such as Nubain or Numorphan, or an epidural
anesthesia.
As the cervix dilates to 8–9 cm, the phase called
the transition begins. This refers to the transition from
the first phase (during which the cervix dilates from
0–10 cm) and the second phase (during which the baby
is pushed out through the birth canal). As the baby’s
head begins to descend, women begin to feel the urge
to ‘‘push’’ or bear down. Active pushing by the mother
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Childbirth

should not begin until the second phase, since pushing
too early can cause the cervix to swell or to tear and
bleed. The attending healthcare practitioner should
counsel the mother on when to begin to push.
Second stage of labor
As the mother enters the second stage of labor,
her baby’s head appears at the top of the cervix.
Uterine contractions get stronger. The infant passes
down the vagina, helped along by contractions of the
abdominal muscles and the mother’s pushing. Active
pushing by the mother is very important during this
phase of labor. If an epidural anesthetic is being used,
many practitioners recommend decreasing the
amount administered during this phase of labor so
that the mother has better control over her abdominal muscles
When the top of the baby’s head appears at the
opening of the vagina, the birth is nearing completion.
First the head passes under the pubic bone. It fills the
lower vagina and stretches the perineum (the tissues
between the vagina and the rectum). This position is
called ‘‘crowning,’’ since only the crown of the head is
visible. When the entire head is out, the shoulders
follow. The attending practitioner suctions the
baby’s mouth and nose to ease the baby’s first breath.
The rest of the baby usually slips out easily, and the
umbilical cord is cut.
Episiotomy
As the baby’s head appears, the perineum may
stretch so tight that the baby’s progress is slowed
down. If there is risk of tearing the mother’s skin, the
doctor may choose to make a small incision into the
perineum to enlarge the vaginal opening. This is called
an episiotomy. If the woman has not had an epidural
or pudendal block, she will get a local anesthetic to
numb the area. Once the episiotomy is made, the baby
is born with a few pushes.
Third stage
In the final stage of labor, the placenta is pushed
out of the vagina by the continuing uterine contractions. The placenta is pancake shaped and about
10 inches in diameter. It has been attached to the
wall of the uterus and has served to convey nourishment from the mother to the fetus throughout the
pregnancy. Continuing uterine contractions cause it
to separate from the uterus at this point. It is important that all of the placenta be removed from the
uterus. If it is not, the uterine bleeding that is normal
after delivery may be much heavier.
838

Stage 2: Expulsion of the fetus

Stage 2: Expulsion of the fetus. (Illustration by Hans & Cassady.)

Placenta
being
detached
Umbilical
cord

Stage 3: Expulsion of the placenta

Stage 3: Expulsion of the placenta. (Illustration by Hans &
Cassady.)

Breech presentation
Approximately 4% of babies are in what is called
the ‘‘breech’’ position when labor begins. In breech
presentation, the baby’s head is not the part pressing
against the cervix. Instead the baby’s bottom or legs
are positioned to enter the birth canal instead of the
head. An obstetrician may attempt to turn the baby to
a head down position using a technique called version.
This is only successful approximately half the time.
The risks of vaginal delivery with breech presentation are much higher than with a head-first presentation. The mother and attending practitioner will need
to weigh the risks and make a decision on whether to
deliver via a cesarean section or attempt a vaginal
birth. The extent of the risk depends to a great extent
on the type of breech presentation, of which there are
three. Frank breech (the baby’s legs are folded up
against its body) is the most common and the safest
for vaginal delivery. The other types are complete
GALE ENCYCLOPEDIA OF MEDICINE

Even in complete breech, other factors should be
met before considering a vaginal birth. An ultrasound
examination should be done to be sure the baby does
not have an unusually large head and that the head is
tilted forward (flexed) rather than back (hyperextended). Fetal monitoring and close observation of
the progress of labor are also important. A slowing
of labor or any indication of difficulty in the body
passing through the pelvis should be an indication
that it is safer to consider a cesarean section.
Forceps delivery
If the labor is not progressing as it should or if the
baby appears to be in distress, the doctor may opt for a
forceps delivery. A forceps is a spoon-shaped device
that resembles a set of salad tongs. It is placed around
the baby’s head so the doctor can pull the baby gently
out of the vagina.
Forceps can be used after the cervix is fully
dilated, and they might be required if:


the umbilical has dropped down in front of the baby
into the birth canal



the baby is too large to pass through the birth canal
unaided



the baby shows signs of stress



the mother is too exhausted to push

Before placing the forceps around the baby’s
head, pain medication or anesthesia may be given to
the mother. The doctor may use a catheter to empty
the mother’s bladder, and may clean the perineal area
with soapy water. Often an episiotomy is done before a
forceps birth, although tears can still occur.
The obstetrician slides half of the forceps at a time
into the vagina and around the side of the baby’s head
to gently grasp the head. When both ‘‘tongs’’ are in
place, the doctor pulls on the forceps to help the baby
through the birth canal as the uterus contracts.
Sometimes the baby can be delivered this way after
the very next contraction.
The frequency of forceps delivery varies from one
hospital to the next, depending on the experience of
staff and the types of anesthesia offered at the hospital.
Some obstetricians accept the need for a forceps delivery as a way to avoid cesarean birth. However, other
obstetrical services do not use forceps at all.
GALE ENCYCLOPEDIA OF MEDICINE

Complications from forceps deliveries can occur.
Sometimes they may cause nerve damage or temporary bruises to the baby’s face. When used by an experienced physician, forceps can save the life of a baby in
distress.
Vacuum-assisted birth
This method of helping a baby out of the birth
canal was developed as a gentler alternative to forceps.
Vacuum-assisted birth can only be used after the cervix is fully dilated (expanded), and the head of the
fetus has begun to descend through the pelvis. In this
procedure, the doctor uses a device called a vacuum
extractor, placing a large rubber or plastic cup against
the baby’s head. A pump creates suction that gently
pulls on the cup to ease the baby down the birth canal.
The force of the suction may cause a bruise on the
baby’s head, but it fades away in a day or so.
The vacuum extractor is not as likely as forceps to
injure the mother, and it leaves more room for the
baby to pass through the pelvis. However, there may
be problems in maintaining the suction during the
vacuum-assisted birth, so forceps may be a better
choice if it is important to remove the baby quickly.
Cesarean sections
A cesarean section, also called a c-section, is a
surgical procedure in which incisions are made
through a woman’s abdomen and uterus to deliver
her baby.
Cesarean sections are performed whenever abnormal conditions complicate labor and vaginal delivery,
threatening the life or health of the mother or the
baby. In 2002, just over 26% of babies were born by
c-section, an increase of 7% from the previous year.
The procedure may be used in cases where the
mother has had a previous c-section and the area of
the incision has been weakened. Dystocia, or difficult
labor, is the another common reason for performing a
c-section.
Difficult labor is commonly caused by one of the
three following conditions: abnormalities in the
mother’s birth canal; abnormalities in the position of
the fetus; abnormalities in the labor, including weak or
infrequent contractions.
Another major factor is fetal distress, a condition
where the fetus is not getting enough oxygen. Fetal
brain damage can result from oxygen deprivation.
Fetal distress is often related to abnormalities in the
position of the fetus, or abnormalities in the birth canal,
causing reduced blood flow through the placenta.
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Childbirth

breech (in which the baby’s legs are crossed under and
in front of the body) and footling breech (in which one
leg or both legs are positioned to enter the birth canal).
These are not considered safe to attempt vaginal
delivery.

Childbirth

Other conditions also can make c-section advisable, such as vaginal herpes, hypertension (high blood
pressure) and diabetes in the mother. Some parents
choose to have a c-section because they fear the pain or
unpredictability of labor or they want to avoid pelvic
damage.

Causes and symptoms
One of the first signs of approaching childbirth
may be a ‘‘bloody show,’’ the appearance of a small
amount of blood-tinged mucus released from the cervix as it begins to dilate. This is called the ‘‘mucus
plug.’’
The most common sign of the onset of labor is
contractions. Sometimes women have trouble telling
the difference between true and false labor pains.
True labor pains:


develop a regular pattern, with contractions coming
closer together



last from 15–30 seconds at the onset and get progressively stronger and longer (up to 60 seconds)



may get stronger with physical activity



occur high up on the abdomen, radiating throughout
the abdomen and lower back

Another sign that labor is beginning is the breaking of the ‘‘bag of waters,’’ the amniotic sac which had
cushioned the baby during the pregnancy. When it
breaks, it releases water in a trickle or a gush. Only
about 10% of women actually experience this water
flow in the beginning of labor, however. Most of the
time, the rupture occurs sometime later in labor. If the
amniotic sac doesn’t rupture on its own, the doctor
will break it during labor.
Some women have diarrhea or nausea as labor
begins. Others notice a sudden surge of energy and
the urge to clean or arrange things right before labor
begins; this is known as ‘‘nesting.’’

Diagnosis
The onset of labor can be determined by measuring how much the cervix has dilated. The degree of
dilation is estimated by feeling the opening cervix
during a pelvic exam. Dilation is measured in centimeters, from zero to 10. Contractions that cause the
cervix to dilate are the sign of true labor.
Fetal monitoring
Fetal monitoring is a process in which the baby’s
heart rate is monitored for indicators of stress during
840

labor and birth. There are several types of fetal
monitoring.
A special stethoscope called a fetoscope may be
used. This is a simple and non-invasive method.
The Doppler method uses ultrasound; it involves
a handheld listening device that transmits the sounds
of the heart rate through a speaker or into an attached
ear piece. It can usually pick up the heart sounds
12 weeks after conception. This method offers intermittent monitoring. It allows the mother freedom to
move about and is also useful during contractions.
Electronic fetal monitoring uses ultrasound and
provides a view of the heartbeat in relationship to the
mother’s contractions. It can be used either continuously or intermittently. It is often used in high risk
pregnancies, and is not often recommended for low
risk ones because it renders the mother immobile and
requires interpretation.
Internal monitoring does not use ultrasound, is
more accurate than electronic monitoring and provides continuous monitoring for the high risk mother.
This requires the mother’s water to be broken and that
she be two to three centimeters dilated. It is used in
high-risk situations only.
Telemetry monitoring is the newest type of monitoring. It uses radio waves transmitted from an instrument on the mother’s thigh. The mother is able to
remain mobile. It provides continuous monitoring
and is used in high-risk situations.

Treatment
Most women choose some type of pain relief during childbirth, ranging from relaxation and imagery to
drugs. The specific choice may depend on what’s available, the woman’s preferences, her doctor’s recommendations, and how the labor is proceeding. All
drugs have some risks and some advantages.
Regional anesthetics
Regional anesthetics include epidurals and
spinals. In this technique, medication is injected into
the space around the spinal nerves. Depending on the
type of medications used, this type of anesthesia can
block nerve signals, causing temporary pain relief, or a
loss of sensation from the waist down. An epidural or
spinal block can provide complete pain relief during
cesarean birth.
An epidural is placed with the woman lying on her
side or sitting up in bed with the back rounded to
allow more space between the vertebrae. Her back is
GALE ENCYCLOPEDIA OF MEDICINE

This type of anesthesia provides complete pain
relief, and can help conserve a woman’s energy, since
she can relax or even sleep during labor. This type of
anesthesia requires an IV and fetal monitor. It may be
harder for a woman to bear down when it comes time
to push, although the amount of anesthesia can be
adjusted as this stage nears.
Spinal anesthesia operates on the same principle
as epidural anesthesia, and is used primarily in cases of
c-section delivery. It is administered in the same way as
an epidural, but the catheter is not left in place. The
amount of anesthetic injected is large, since it must be
injected at one time. Because of the anesthetic’s effect
on motor nerves, most women using it cannot push
during delivery. This is a disadvantage in labor, but
not an issue during a c-section. Spinals provide quick
and strong anesthesia and allow for major abdominal
surgery with almost no pain.
Narcotics
Short-acting narcotics can ease pain and do not
interfere with a woman’s ability to push. However,
they can cause sedation, dizziness, nausea, and vomiting. Narcotics cross the placenta and may slow down a
baby’s breathing; they can’t be given too close to the
time of delivery.
Natural childbirth and preparation for childbirth
There are several methods to prepare for childbirth. The one selected often depends on what is available through the healthcare provider. Overall, family
involvement is receiving increased attention by the
healthcare systems, and many hospitals now offer
birthing rooms and maternity centers to help the entire
family. There are several choices available for childbirth preparation.
Lamaze, or Lamaze-Pavlov, is the most common
in the United States today. It was the first popular
natural childbirth method, becoming popular in the
1960s. Breathing exercises and concentration on a
focal point are practiced to allow mothers to control
pain while maintaining consciousness. This allows the
flow of oxygen to the baby and to the muscles in the
uterus to be maintained. A partner coaches the mother
throughout the birthing process.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Amniotic sac—The membranous sac that surrounds the embryo and fills with watery fluid as
pregnancy advances.
Breech birth—Birth of a baby bottom-first, instead
of the usual head first delivery. This can add to
labor and delivery problems because the baby’s
bottom doesn’t mold a passage through the birth
canal as well as does the head.
Cervix—A small cylindrical organ about an inch or so
long and less than an inch around that makes up the
lower part and neck of the uterus. The cervix separates
the body and cavity of the uterus from the vagina.
Embryo—The unborn child during the first eight
weeks of its development following conception.
Gestation—The period from conception to birth,
during which the developing fetus is carried in the
uterus.
Perineum—The area between the thighs that lies
behind the genital organs and in front of the anus.
Placenta—The organ that develops in the uterus
during pregnancy and that links the blood supplies
of mother and baby.

The Read method, named for Dick Read, is a
technique of breathing that was originated in the
1930s to help mothers deal with apprehension and
tension associated with childbirth. This natural childbirth method uses different breathing for the different
stages of childbirth.
The LeBoyer method stresses a relaxed delivery
in a quiet, dim room. It attempts to avoid overstimulation of the baby and to foster mother-child bonding
by placing the baby on the mother’s abdomen and
having the mother massage him or her immediately
after the birth. Then the father washes the baby in a
warm bath.
The Bradley method is called father-coached
childbirth, because it focuses on the father serving as
coach throughout the process. It encourages normal
activities during the first stages of labor.
Resources
PERIODICALS

Stevens, Laura Roe. ‘‘Gimme a C: Is Choosing a Cesarean
Section for a Nonmedical Reason Wise?’’ Fit Pregnancy
April-May 2004: 40–42.
841

Childbirth

scrubbed with antiseptic, and a local anesthetic is
injected in the skin to numb the site. The needle is
inserted between two vertebrae and through the
tough tissue in front of the spinal column. A catheter
is put in place that allows continuous doses of anesthetic to be given.

Children’s health

ORGANIZATIONS

American Academy of Husband-Coached Childbirth. P.O.
Box 5224, Sherman Oaks, CA 91413. (800) 423-2397; in
California (800) 422-4784.
American Society for Prophylaxis in Obstetrics/LAMAZE
(ASPO/LAMAZE). 1840 Wilson Blvd., Ste. 204,
Arlington, VA 22201. (800) 368-4404.
Childbirth Education Foundation. P.O. Box 5, Richboro,
PA 18954. (215) 357-2792.
International Association of Parents and Professionals for
Safe Alternatives in Childbirth. Rte. 1, Box 646, Marble
Hill, MO 63764. (314) 238-2010.
International Childbirth Education Association. P.O. Box
20048, Minneapolis, MN 55420. (612) 854-8660.
Postpartum Support International. 927 North Kellogg Ave.,
Santa Barbara, CA 93111. (805) 967-7636.

Carol A. Turkington
Teresa G. Odle

Childhood disintegrative disorder see
Pervasive developmental disorders

I Children’s health
Definition
Children’s health encompasses the physical, mental, emotional, and social well-being of children from
infancy through adolescence.



Inactivated Polio. Three doses.



Pneumococcal Conjugate. Three doses.



Measles, Mumps, Rubella (MMR). One dose.



Varicella (chickenpox). One dose.



Hepatitis A. (In certain geographical areas and with
certain high risk groups.)

The flu vaccine has been added in recent years and
has been recommended for childhood caregivers. It
is not recommended for children younger than
six months of age. A combined vaccine called the
Hexavac includes the vaccine for diphtheria, tetanus,
pertussis, poliomyelitis, H. influenza B, and hepatitis B
in one dose. In clinical trials in 2004, it was shown to be
safe and effective in young children.
Some immunizations may cause mild side effects,
or more rarely, serious adverse reactions. However,
the benefits of immunization greatly outweigh the
incidence of health problems arising from them.
There are serious chronic diseases and health problems that are frequently diagnosed in childhood and
cannot be vaccinated against. These include, but are
not limited to, asthma, type I diabetes (juvenile diabetes), leukemia, hemophilia, and cystic fibrosis.
Mental health
Children who have difficulty in areas of language
acquisition, cognitive development, and behavior control may be suffering from mental illness. Mental
health problems that may afflict children include:


Attention Deficit Hyperactivity Disorder (ADHD).
According to the AAP, 4–12% of school-aged children have ADHD, a condition characterized by poor
impulse control and excessive motor activity.



Learning disorders. Learning disabilities affect one in
10 school children.



Depression, anxiety, and bipolar disorder. Affective,
or mood, disorders can affect kids as well as adults.



Eating disorders. Anorexia nervosa, bulimia nervosa,
and binge eating disorder (BED) frequently occur in
adolescent girls.



Schizophrenia. A disorder characterized by bizarre
thoughts and behaviors, paranoia, impaired sense
of reality, and psychosis may be diagnosed in
childhood.



Obsessive-compulsive disorder. Also called OCD, this
anxiety disorder afflicts one in 200 children.



Autism and pervasive developmental disorder.
Severe developmental disabilities that cause a child
to become withdrawn and unresponsive.

Description
All children should have regular well-child check
ups according to the schedule recommended by their
physician or pediatrician. The American Academy of
Pediatrics (AAP) advises that children be seen for wellbaby check ups at two weeks, two months, four
months, six months, nine months, twelve months, fifteen months, and eighteen months. Well-child visits
are recommended at ages two, three, four, five, six,
eight, 10, and annually thereafter through age 21.
In addition, an immunization schedule should be
followed to protect against disease and infection. As of
2004, the AAP and the U.S. Centers for Disease
Control (CDC) recommended that the following
childhood immunizations be administered by age two:


Hepatitis B. Three doses.



Diphtheria, Tetanus, and Pertussis (DTaP). Four
doses.



H. influenzae type b (Hib). Four doses.

842

GALE ENCYCLOPEDIA OF MEDICINE

the raising of infants and children. He began medical
school at Yale University in 1925, and transferred to
Columbia University’s College of Physicians and
Surgeons in 1927. Spock had decided well before starting
his medical studies that he would "work with children,
who have their whole lives ahead of them" and so, upon
taking his M.D. degree in 1929 and serving his general
internship at the prestigious Presbyterian Hospital, he specialized in pediatrics at a small hospital crowded with
children in New York’s Hell’s Kitchen area.

Benjamin Spock, pediatrician and political activist,
was most noted for his authorship of Baby and Child Care,
which significantly changed predominant attitudes toward

On a summer vacation in 1943 he began to write his
most famous book and he continued to work on it from
1944 to 1946 while serving as a medical officer in the
Navy. The book sharply broke with the authoritarian
tone and rigorous instructions found in earlier generations
of baby-care books, most of which said to feed infants on a
strict schedule and not to pick them up when they cried.
Spock, who spent ten years trying to reconcile his psychoanalytic training with what mothers were telling him about
their children, told his readers, ‘‘You know more than you
think you do. . . . Don’t be afraid to trust your own common
sense. . . . Take it easy, trust your own instincts, and follow
the directions that your doctor gives you.’’ The response
was overwhelming. Baby and Child Care rapidly became
America’s all-time best-seller except for Shakespeare and
the Bible; by 1976 it had also eclipsed Shakespeare.

Leading Causes Of Death In Adolescents

start to be influenced by their peers, and begin to
show interest in the opposite sex.

(Library of Congress.)

Motor vehicle crashes
Suicide (numbers 2 and 3 are approximately equal)
Homicide
Poisoning (which includes accidental poisonings due to alcohol or other drug
overdose)
Drowning



Mental retardation. Children under age 18 with an IQ
of 70 or below and impairments in adaptive functioning are considered mentally retarded.

Factors which can have a negative impact on the
emotional and social well-being of children include:


Violence. Bullying can cause serious damage to a
child’s sense of self-esteem and personal safety, as
can experiences with school violence.



Family turmoil. Divorce, death, and other lifechanging events that alter the family dynamic can
have a serious impact on a child. Even a positive
event such as the birth of a sibling or a move to a new
city and school can put emotional strain on a child.



Stress. The pressure to perform well academically
and in extracurricular activities such as sports can
be overwhelming to some children.



Peer pressure. Although it can have a positive
impact, peer pressure is often a source of significant
stress for children. This is particularly true in adolescence when ‘‘fitting in’’ seems all-important.



Drugs and alcohol. Curiosity is intrinsic to childhood, and more than 30% of children have experimented with alcohol by age 13. Open communication

Emotional and social health
Children take their first significant steps toward
socialization and peer interaction when they begin to
engage in cooperative play at around age four. Their
social development will progress throughout childhood and adolescence as they develop friendships,
GALE ENCYCLOPEDIA OF MEDICINE

843

Children’s health

D R . B E N J A M I N S P O C K (1903–1998)

Children’s health

Leading Causes Of Illness/Injury In Adolescents

Trauma (this could be anything from sports-related injuries to gunshot
wounds; alcohol or other drug abuse is frequently a factor)
Mental health issues (substance abuse, depression, etc.)
Sexually transmitted infections
Acquired immunodeficiency syndrome (AIDS)
Eating disorders

with children that sets forth parental expectations
about drug and alcohol use is essential.


Negative sexual experiences. Sexual abuse and
assault can emotionally scar a child and instill negative feelings about sexuality and relationships.

Causes and symptoms
Childhood health problems may be congenital
(i.e., present at birth) or acquired through infection,
immune system deficiency, or another disease process.
They may also be caused by physical trauma (e.g., a
car accident or a playground fall) or a toxic substance
(e.g., an allergen, drug, or poisonous chemical), or
triggered by genetic or environmental factors.
Physical and mental health problems in childhood
can cause a wide spectrum of symptoms. However, the
following behaviors frequently signify a larger emotional, social, or mental disturbance:


signs of alcohol and drug use



falling grades



lack of interest in activities that were previously
enjoyable to the child



excessive anxiety



persistent, prolonged depression



withdrawal from friends and family



violence



temper tantrums or inappropriate displays of anger



self-inflicted injury



bizarre behavior and/or speech



trouble with the police



sexual promiscuity



suicide attempts

The causes of developmental disorders and delays
and learning disabilities are not always fully understood. Pervasive developmental disorder (PDD) and
844

autistic spectrum disorder (more commonly known as
autism) are characterized by unresponsiveness and
severe impairments in one or more of the following
areas:


Social interaction. Autistic children are often unaware of acceptable social behavior and are withdrawn and socially isolated. They frequently do not
like physical contact.



Communication and language. A child with autism
or PDD may not speak or may display limited or
immature language skills.



Behavior. Autistic or PDD children may have difficulty dealing with anger, can be self-injurious, and
may display obsessive behavior.

Autism is associated with brain abnormalities, but
the exact mechanisms that trigger the disorder are
yet to be determined. It has been linked to certain
congenital conditions such as neurofibromatosis, fragile X syndrome, and phenylketonuria (PKU).

Diagnosis
Physical, intellectual, emotional, and social
maturation are all important markers of a child’s overall health and well-being. When evaluating children,
pediatricians and child-care specialists assess related
skill sets, such as a child’s acquisition and use of
language, fine and gross motor skills, cognitive
growth, and socialization, and achievement of certain
milestones in these areas. A developmental milestone
is a task or skill set that a child is expected to reach
at a certain age or stage of life. For example, by age
one, most children have achieved the physical milestone of walking with the assistance of an adult.
Developmental disorders may be identified and/or
diagnosed by physicians, teachers, child psychologists,
therapists, counselors, and other professionals who
interact with children on a regular basis.
It is important to remember that all children are
unique, and develop at different paces within this
broad framework. Reaching a milestone early or late
does not necessarily indicate a developmental problem. However, if a child is consistently lagging on
achieving milestones, or has a significant deficit in one
developmental area, he or she may be experiencing
developmental delays.
Pediatricians and other medical professionals
typically diagnose physical illness and disease in children. In cases of illness and injury, children will
undergo a thorough physical examination and patient
history. Diagnostic tests may be performed as appropriate. In cases of mental or emotional disorders, a
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Medications may be prescribed to treat certain
childhood illnesses. Proper dosage is particularly
important with infants and children, as medications
such as acetaminophen can be toxic in excessive
amounts. Parents and caregivers should always follow
the instructions for use that accompany medications,
and inform the child’s pediatrician if the child is taking
any other drugs or vitamins to prevent potentially
negative drug interactions. Any side effects or adverse
reactions to medication should be reported to the
child’s physician. If antibiotics are prescribed, the full
course should always be taken.
Other treatments for childhood illness and/or
injuries include, but are not limited to, nutritional
therapy, physical therapy, respiratory therapy, medical devices (e.g., hearing aids, glasses, braces), and in
some cases, surgery.
Counseling is typically a front-line treatment for
psychological disorders. Therapy approaches include
psychotherapy, cognitive therapy, behavioral therapy,
family counseling, and group therapy. Therapy or
counseling may be administered by social workers,
nurses, licensed counselors and therapists, psychologists, or psychiatrists. Psychoactive medication may
also be prescribed for symptom relief in children and
adolescents with mental disorders.
Support groups may also provide emotional support for children with chronic illnesses or mental disorders. This approach, which allows individuals to
seek advice and counsel from others in similar circumstances, can be extremely effective, especially in older
children who look toward their peers for guidance and
support.
Speech therapy may be helpful to children with
developmental delays in language acquisition.
Children with learning disorders can benefit from special education therapy.

Alternative treatment
Therapeutic approaches that encourage selfdiscovery and empowerment may be useful in treating some childhood emotional traumas and mental
GALE ENCYCLOPEDIA OF MEDICINE

disorders. Art therapy, the use of the creative process
to express and understand emotion, encompasses a
broad range of humanistic disciplines, including visual
arts, dance, drama, music, film, writing, literature, and
other artistic genres. It can be particularly effective in
children who may have difficulty gaining insight to
emotions and thoughts they are otherwise incapable
of expressing.
Certain mild herbal remedies may also be safely
used with children, such as ginger (Zingiber officinale)
tea for nausea and aloe vera salve for burns. Parents
and caregivers should always consult their healthcare
provider before administering herbs to children.

Prognosis
The prognosis for childhood health problems varies widely. In general, early detection and proper treatment can greatly improve the odds of recovery from
many childhood ailments.
Some learning disabilities and mild developmental disorders can be overcome or greatly improved
through the therapies discussed above. However, as
of early 2001, there was no known medical treatment
or pharmacological therapy that is capable of completely eliminating all of the symptoms associated with
pervasive developmental disorder (PDD), autism
spectrum disorder, and mental retardation. Mental
illnesses such as schizophrenia and bipolar disorder
are also chronic, lifelong disorders, although their
symptoms can often be well-controlled with
medication.

Prevention
Parents can take some precautions to ensure the
safety of their children. Childproofing the home, following a recommended immunization schedule, educating kids on safety, learning CPR, and taking kids
for regular well-child check-ups can help to protect
against physical harm. In addition, encouraging open
communication with children can help them grow
both emotionally and socially. Providing a loving
and supportive home environment can help to nurture
an emotionally healthy child who is independent, selfconfident, socially skilled, insightful, and empathetic
towards others.
Because they are still developing motor skills, kids
can be particularly accident prone. Observing the following safety rules can help protect children from
injury:


Helmets and padding. Children should always wear a
properly fitted helmet and appropriate protective
845

Children’s health

psychologist or other mental healthcare professional
will meet with the patient to conduct an interview and
take a detailed social and medical history. Interviews
with a parent or guardian may also be part of the
diagnostic process. The physician may also administer
one or more psychological tests (also called clinical
inventories, scales, or assessments).

Children’s health

gear when riding a bike, scooter, or similar equipment or participating in sports. They should also ride
on designated bike paths whenever possible, and
learn bicycle safety rules (i.e., ride with traffic, use
hand signals).


Playground safety. Swing sets and other outdoor
play equipment should be well-maintained have at
least 12 in (30 cm) of loose fill materials (e.g., sand,
wood chips) underneath to cushion falls, and children should always be properly supervised at play.



Staying apprised of recalls. Children’s toys, play
equipment, and care products are frequently
involved in product recalls. The U.S. Consumer
Safety Products Commission (CSPC) is the agency
responsible for tracking these recalls (see Resources
below).



Staying safe in the car. Up to 85% of children’s car
seats are improperly installed and/or used. Infants
should always be in a rear-facing car seat until they
are over 12 months of age and weigh more than 20 lb
(9 kg). An infant or car seat should never be put in a
front passenger seat that has an air bag. Once they
outgrow their forward facing car seats, children
between the ages of four and eight who weigh
between 40–80 lb (18–36 kg) should ride in a booster
seat. Every child who rides in a car over this age and
weight should buckle up with a properly fitted lap
and shoulder belt.



Teaching children pedestrian safety. Younger children should never be allowed to cross the street by
themselves, and older kids should know to follow
traffic signs and signals, cross the street at the corner,
and look both ways before stepping off the curb.



Teaching children about personal safety. Kids
should know what to do in case they get lost or are
approached by a stranger. It is also imperative that
parents talk openly with their children about their
body and sexuality, and what behavior is inappropriate, to protect them against sexual predators.

KEY TERMS
Bipolar disorder—Manic depressive disorder.
A mood disorder characterized by manic highs
and depressive lows.
Child development—The process of physical, intellectual, emotional, and social growth that occurs
from infancy through adolescence. Erik Erikson,
Margaret Mahler, Sigmund Freud, and Jean Piaget
are among the most well-known child development
theorists.
CPR—Cardiopulmonary resuscitation. A first aid
technique designed to stimulate breathing and
blood flow through a combination of chest compressions and rescue breathing.
Immunization—Creating immunity to a disease
through a vaccine injection that stimulates the production of antibodies.
Learning disabilities—An impairment of the cognitive processes of understanding and using spoken
and written language that results in difficulties with
one or more academic skill sets (e.g., reading, writing, mathematics).
Motor skills—Controlled movement of muscle
groups. Fine motor skills involve tasks that require
dexterity of small muscles, such as buttoning a shirt.
Tasks such as walking or throwing a ball involve the
use of gross motor skills.
Obsessive-compulsive disorder—Also known as
OCD; a disorder characterized by obsessive
thoughts (e.g., fear of contamination) and compulsive behaviors (e.g., repetitive hand washing) that
cause distress and/or functional impairment.
Psychological tests—Written, verbal, or visual
tasks that assess psychological functioning, intelligence, and/or personality traits.
Type 1 diabetes—A chronic immune system disorder in which the pancreas does not produce sufficient amounts of insulin, a hormone that enables
cells to use glucose for energy. Also called juvenile
diabetes, it must be treated with insulin injections.

Child-proofing the household is also an important
step toward keeping kids healthy. To make a house a
safe home, parents and caregivers should:


Ban guns. Accidental shootings in the home injure an
estimated 1,500 children under age 14 each year. If a
gun must be in the home, it should be securely locked
in a tamper proof box or safe.



Keep all matches, lighters, and flammable materials
properly stored and out of the reach of children.



Make sure hot water heaters are set to 120 degrees or
below to prevent scalding injuries.

846



Equip the home with working fire extinguishers and
smoke alarms, and teach children what to do in case
of fire.



Secure all medications (including vitamins, herbs,
and supplements), hazardous chemicals, and poisonous substances (including alcohol and tobacco).
GALE ENCYCLOPEDIA OF MEDICINE

Don’t smoke. Aside from causing cancer and other
health problems in smokers, second-hand smoke is
hazardous to a child’s health.



Keep small children away from poisonous plants
outdoors, and remove any indoor plants that are
toxic.



Post the phone numbers of poison control and the
pediatrician near the phone, and teach children
about dialing 9-1-1 for emergencies.



Children under age five should never be left alone in
the bathtub, wading pool, or near any standing water
source (including an open toilet). Drowning is the
leading cause of death by injury for children between
the ages of one and four.



Remove lead paint. Lead is a serious health hazard
for children, and houses built before 1978 should be
tested for lead paint. If lead is found, the paint should
be removed using the appropriate safety precautions.

These safety guidelines are not all-inclusive, and
there are many age-specific safety precautions that
parents and guardians of children should observe.
For example, infants should never be left with a
propped-up bottle in their mouths or given small
play items because of the choking hazards involved.
Resources
BOOKS

Holtzman, Debra Smiley. The Panic Proof Parent. Chicago:
NTC/Contemporary, 2000.
Pasquariello, Patrick S., Jr., editor. The Children’s Hospital
of Philadelphia: Book of Pregnancy and Child Care. New
York: John Wiley & Sons, Inc., 1999.
PERIODICALS

‘‘Immunization Practices Group Recommends Flu Vaccine
for Young Children.’’ Medical Letter on the CDC &
FDA May 30, 2004: 68.
‘‘Vaccine Against Six Diseases is Safe and Effective in
Children.’’ Obesity, Fitness & Wellness Week June 26,
2004: 76.
ORGANIZATIONS

National Institute of Mental Health. 6001 Executive
Boulevard, Rm. 8184, MSC 9663, Bethesda, MD
20892-9663. (301) 443-4513.
National SAFE KIDS Campaign. Children’s National
Medical Center. (202) 662-0600. <http://
www.safekids.org>.
U.S. Consumer Products Safety Commission (CPSC). 4330
East-West Highway, Bethesda, MD 20814-4408.
Consumer Hotline: (800) 638-2772. <http://
www.cpsc.gov>.

Paula Anne Ford-Martin
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Chinese traditional herbal medicine see
Traditional Chinese herbalism
Chinese traditional medicine see Traditional
Chinese medicine

I Chiropractic
Definition
Chiropractic is from Greek words meaning done
by hand. It is grounded in the principle that the body
can heal itself when the skeletal system is correctly
aligned and the nervous system is functioning properly. To achieve this, the practitioner uses his or her
hands or an adjusting tool to perform specific manipulations of the vertebrae. When these bones of the
spine are not correctly articulated, resulting in a condition known as subluxation, the theory is that nerve
transmission is disrupted and causes pain in the back,
as well as other areas of the body.
Chiropractic is one of the most popular alternative
therapies currently available. Some would say it now
qualifies as mainstream treatment as opposed to complementary medicine. Chiropractic treatment is covered
by many insurance plans and in 2004, the U.S.
Department of Veterans Affairs announced full inclusion of chiropractic care for veterans. It has become
well-accepted treatment for acute pain and problems of
the spine, including lower back pain and whiplash.
Applications beyond that scope are not supported by
current evidence, although there are ongoing studies
into the usefulness of chiropractic for such problems
as ear infections, dysmenorrhea, infant colic, migraine
headaches, and other conditions.

Purpose
Most people will experience back pain at some time
in their lives. Injuries due to overexertion and poor
posture are among the most common. Depending on
the cause and severity of the condition, options for
treatment may include physical therapy, rest, medications, surgery, or chiropractic care. Chiropractic treatment carries none of the risks of surgical or
pharmacologic treatment. Practitioners use a holistic
approach to health. The goal is not merely to relieve
the present ailment, but to analyze the cause and recommend appropriate changes of lifestyle to prevent the
problem from occurring again. They believe in a risk/
benefit analysis before use of any intervention. The odds
847

Chiropractic



Chiropractic

D A N I E L P A L M E R (1845–1913)
Chiropractic inventor, Daniel David Palmer, was
born on March 7, 1845, in Toronto, Ontario. He was
one of five siblings, the children of a shoemaker and his
wife, Thomas and Katherine Palmer. Daniel Palmer and
his older brother fell victim to wanderlust and left Canada
with a tiny cash reserve in April 1865. They immigrated to
the United States on foot, walking for 30 days before
arriving in Buffalo, New York. They traveled by boat
through the St. Lawrence Seaway to Detroit, Michigan.
There they survived by working odd jobs and sleeping on
the dock. Daniel Palmer settled in What Cheer, Iowa,
where he supported himself and his first wife as a grocer
and fish peddler in the early 1880s. He later moved to
Davenport, Iowa, where he raised three daughters and
one son.

nine years he investigated the relationship between magnetism and disease. Palmer felt that there was one thing
that caused disease. He was intent upon discovering this
one thing, or as he called it: the great secret.

Palmer was a man of high curiosity. He investigated a
variety of disciplines of medical science during his lifetime, many of which were in their infancy. He was intrigued by phrenology and assorted spiritual cults, and for

Palmer, who was married six times during his life,
died in California in 1913; he was destitute. His son,
Bartlett Joshua Palmer, successfully commercialized the
practice of chiropractic.

of an adverse outcome are extremely low. Chiropractic
has proven in several studies to be less expensive than
many more traditional routes such as outpatient physical therapy. Relief from some neuromuscular problems
is immediate, although a series of treatments is likely
to be required to maintain the improvement. Spinal
manipulation is an excellent option for acute lower
back pain, and may also relieve neck pain as well as
other musculoskeletal pain. Although most back pain
will subside eventually with no treatment at all, chiropractic treatment can significantly shorten the time it
takes to get relief. Some types of headache can also be
successfully treated by chiropractic.

through the spinal canal, and areas that are poorly
aligned or under stress can cause physical symptoms
both in the spine and in other areas of the body. Thus
the body has the innate intelligence to heal itself when
unencumbered by spinal irregularities causing nerve
interference. After his success with Lillard, other
patients began coming to him for care, and responded
well to adjustments. This resulted in Palmer’s further
study of the relationship between an optimally functional spine and normal health.

Description
Origins
Spinal manipulation has a long history in many
cultures but Daniel D. Palmer is the founder of modern chiropractic theory, dating back to the 1890s.
A grocer and magnetic healer, he applied his knowledge of the nervous system and manual therapies in an
unusual situation. One renowned story concerns
Harvey Lillard, a janitor in the office where Palmer
worked. The man had been deaf for 17 years, ever
since he had sustained an injury to his upper spine.
Palmer performed an adjustment on a painful vertebra
in the region of the injury and Lillard’s hearing was
reputedly restored. Palmer theorized that all communication from the brain to the rest of the body passes
848

In September 1895, Palmer purported to have cured a
deaf man by placing pressure on the man’s displaced
vertebra. Shortly afterward Palmer claimed to cure another
patient of heart trouble, again by adjusting a displaced
vertebra. The double coincidence led Palmer to theorize
that human disease might be the result of dislocated or
luxated bones, as Palmer called them. That same year he
established the Palmer School of Chiropractic where he
taught a three-month course in the simple fundamentals of
medicine and spinal adjustment.

Palmer founded the first chiropractic college in
1897. His son, B. J. Palmer, continued to develop
chiropractic philosophy and practice after his father’s
death. B. J. and other faculty members were divided
over the role of subluxation in disease. B. J. saw it as
the cause of all disease. The others disagreed and
sought a more rational way of thinking, thus broadening the base of chiropractic education. From 1910 to
1920, many other chiropractic colleges were established. Other innovators, including John Howard,
Carl Cleveland, Earl Homewood, Joseph Janse,
Herbert Lee, and Claude Watkins, also helped to
advance the profession.
The theories of the Palmers receive somewhat
broader interpretation today. Many chiropractors
believe that back pain can be relieved and health
restored through chiropractic treatment even in
patients who do not have demonstrable subluxations.
Scientific development and research of chiropractic is
GALE ENCYCLOPEDIA OF MEDICINE

Chiropractic

gaining momentum. The twenty-first century will
likely see the metaphysical concepts such as innate
intelligence give way to more scientific proofs and
reform.
Many people besides the Palmers have contributed to the development of chiropractic theory and
technique. Some have gone on to create a variety of
procedures and related types of therapy that have their
roots in chiropractic, including McTimoney-Corley
chiropractic, craniosacral manipulation, naprapathy,
and applied kinesiology. Osteopathy is another related
holistic discipline that utilizes spinal and musculoskeletal manipulation as a part of treatment, but osteopathic training is more similar in scope to that of
an M.D.
Initial visit
An initial chiropractic exam will most often include
a history and a physical. The patient should be asked
about the current complaint, whether there are chronic
health problems, family history of disease, dietary
habits, medical care received, and any medications currently being taken. Further, the current complaint
should be described in terms of how long it has been a
problem, how it has progressed, and whether it is the
result of an injury or occurred spontaneously. Details
of how an injury occurred should be given. The physical
exam should evaluate by observation and palpation
whether the painful area has evidence of inflammation
or poor alignment. Range of motion may also be
assessed. In the spine, either hypomobility (fixation)
or hypermobility may be a problem. Laboratory analysis is helpful in some cases to rule out serious infection
or other health issues that may require referral for
another type of treatment. Many practitioners also
insist on x rays during the initial evaluation
Manipulation
When spinal manipulation is employed, it is generally done with the hands, although some practitioners may use an adjusting tool. A classic adjustment
involves a high velocity, low amplitude thrust that produces a usually painless popping noise, and improves
the range of motion of the joint that was treated. The
patient may lie on a specially designed, padded table
that helps the practitioner to achieve the proper positions for treatment. Some adjustments involve manipulating the entire spine, or large portions of it, as a
unit; others are small movements designed to affect a
single joint. Stretching, traction, and slow manipulation
are other techniques that can be employed to restore
structural integrity and relieve nerve interference.
GALE ENCYCLOPEDIA OF MEDICINE

An example of a McTimoney chiropractic technique on
patient’s lumbar vertebra. The McTimoney chiropractic is a
system of adjustment by hand of displacements of the spinal
column and bones. It can also be applied to animals.
(Photograph by Francoise Sauze, Custom Medical Stock Photo.
Reproduced by permission.)

A new use of technology with traditional chiropractic care has been introduced. Using a hand-held
device that is pressed to the spine or joints, a chiropractor may soon be able to detect and manipulate the
skeleton not only with his or her hands but with the
computer-linked device that uses harmonic frequencies to detect a misalignment in the spine. The new
technology was not widely accepted in 2004, however.
Length of treatment
The number of chiropractic treatments required will
vary depending on several factors. Generally longerterm treatment is needed for conditions that are chronic,
severe, or occur in conjunction with another health
problem. Patients who are not in overall good health
may also have longer healing times. Some injuries will
849

Chiropractic

inherently require more treatments than others in order
to get relief. Care is given in three stages. Initially
appointments are more frequent with the goal of relieving immediate pain. Next, the patient moves into a
rehabilitative stage to continue the healing process and
help to prevent a relapse. Finally, the patient may elect
periodic maintenance, or wellness treatments, along
with lifestyle changes if needed to stay in good health.
Follow-up care
Discharge and follow-up therapy are important.
If an injury occurred as a result of poor fitness or
health, a program of exercise or nutrition should be
prescribed. Home therapy may also be recommended,
involving such things as anti-inflammatory medication and applications of heat or ice packs. Conscious
attention to posture may help some patients avoid
sustaining a similar injury in the future, and the chiropractor should be able to discern what poor postural
habits require correction. A sedentary lifestyle, particularly with a lot of time spent sitting, is likely to
contribute to poor posture and may predispose a person to back pain and injury.
Types of practitioners
Some practitioners use spinal manipulation to the
exclusion of all other modalities, and are known as
straight chiropractors. Others integrate various types
of therapy such as massage, nutritional intervention,
or treatment with vitamins, herbs, or homeopathic
remedies. They also embrace ideas from other health
care traditions. This group is known as mixers. The
vast majority of chiropractors, perhaps 85%, fall in
this latter category.

Preparations
Patients should enter the chiropractic clinic with
an open mind. This will help to achieve maximum
results.

Precautions
Chiropractic is not an appropriate therapy for diseases that are severely degenerative and may require
medication or surgery. Many conditions of the spine
are amenable to manipulative treatment, but this does
not include fractures. The practitioner should be
informed in advance if the patient is on anticoagulants,
or has osteoporosis or any other condition that may
weaken the bones. Other circumstances might suggest
the patient should not have chiropractic care. These
should be detected in the history or physical exam. In
850

addition to fractures, Down syndrome, some congenital
defects, and some types of cancer are a few of the things
that may preclude spinal manipulation. On rare occasions, a fracture or dislocation may occur. There is also
a very slim possibility of experiencing a stroke as a
result of spinal manipulation, but estimates are that
it is no more frequent than 2.5 occurrences per one
million treatments.
Patients should be wary of chiropractors who
insist on costly x rays and repeated visits with no end
in sight. Extensive use is not scientifically justifiable,
especially in most cases of lower back pain. There are
some circumstances when x rays are indicated, including acute or possibly severe injuries such as those that
might result from a car accident.

Side effects
It is not uncommon to have local discomfort in the
form of aches, pains, or spasms for a few days following a chiropractic treatment. Some patients may also
experience mild headache or fatigue that resolves
quickly.

Research and general acceptance
As recently as the 1970s, the American Medical
Association (a national group of medical doctors) was
quite hostile to chiropractic. AMA members were
advised that it was unethical to be associated with
chiropractors. Fortunately that has changed, and
as of 2000, many allopathic or traditionally trained
physicians enjoy cordial referral relationships with
chiropractors. The public is strongly in favor of chiropractic treatment. Chiropractors see the lion’s share of
all patients who seek medical help for back problems.
And chiropractic treatment is the most widely used of
all alternative medical treatments.
Research has also supported the use of spinal
manipulation for acute low back pain. There is some
anecdotal evidence recommending chiropractic treatment for ailments unrelated to musculoskeletal problems, but there is not enough research-based data to
support this. On the other hand, a chiropractor may be
able to treat problems and diseases unrelated to the
skeletal structure by employing therapies other than
spinal manipulation.
Although many chiropractors limit their practice
to spine and joint problems, others claim to treat disorders that are not closely related to the back or
musculoskeletal system. These include asthma, bedwetting, bronchitis, coughs, dizziness, dysmenorrhea,
earache, fainting, headache, hyperactivity, indigestion,
GALE ENCYCLOPEDIA OF MEDICINE

Adjustment—A specific type of manipulation of
the spine designed to return it to proper structural
and functional form.
Allopathic—Conventional practice of medicine
generally associated with M.D. physicians.
Dysmenorrhea—Painful menstruation.
Osteoporosis—A condition of decreased bone
density, causing increased bone fragility, that is
most common in elderly women.
Subluxation—Misalignment between vertebrae
that structurally and functionally impairs nerve
function.

infertility, migraine, pneumonia, and issues related to
pregnancy. There are at least three explanations for the
possible effectiveness for these conditions. One is that
the problem could be linked to a nerve impingement,
as may be possible with bed-wetting, dizziness, fainting, and headache. In a second group, chiropractic
treatment may offer some relief from complicating
pain and spasms caused by the disease process, as
with asthma, bronchitis, coughs, and pneumonia.
The discomforts of pregnancy may also be relieved
with gentle chiropractic therapy. A third possibility is
that manipulation or use of soft-tissue techniques may
directly promote improvement of some conditions.
One particular procedure, known as the endonasal
technique, is thought to help the eustachian tube to
open and thus improve drainage of the middle ear. The
tube is sometimes blocked off due to exudates or
inflammatory processes. This can offer significant
relief from earaches. Some headaches also fall in this
category, as skilled use of soft tissue techniques and
adjustment may relieve the muscle tension that may
initiate some headaches.
Dysmenorrhea, hyperactivity, indigestion, and
infertility are said to be relieved as a result of improved
flow of blood and nerve energy following treatment.
Evidence for this is anecdotal at best, but manipulation is unlikely to be harmful if causes treatable by
other modalities have been ruled out.
For conditions such as cancer, fractures, infectious diseases, neurologic disease processes, and anything that may cause increased orthopedic fragility,
chiropractic treatment alone is not an effective therapy, and may even be harmful in some cases. Those
who have known circulatory problems, especially
GALE ENCYCLOPEDIA OF MEDICINE

with a history of thrombosis, should not have spinal
manipulation.
Resources
PERIODICALS

‘‘Technology Takes Tiny Steps in Hands-on Chiropractic
Industry.’’ Medical Letter on the CDC & FDA June 20,
2004: 17.
‘‘VA Includes Chiropractic Care for Veterans.’’ Managed
Care Weekly May 3, 2004: 23.
ORGANIZATIONS

American Chiropractic Association. 1701 Clarendon Blvd.,
Arlington, VA 22209. (800) 986-4636. <http://
www.amerchiro.org>.

Judith Turner
Teresa G. Odle

Chlamydial infections see Chlamydial
pneumonia; Epididymitis;
Nongonococcal urethritis; Sexually
transmitted diseases

I Chlamydial pneumonia
Definition
Chlamydial pneumonia refers to one of several
types of pneumonia that can be caused by various
types of the bacteria known as Chlamydia.

Description
Pneumonia is an infection of the lungs. The air
sacs (alveoli) and/or the tissues of the lungs become
swollen, and the alveoli may fill with pus or fluid. This
prevents the lungs from taking in sufficient oxygen,
which deprives the blood and the rest of the body’s
tissues of oxygen.
There are three major types of Chlamydia:
Chlamydia psittaci, Chlamydia pneumoniae, and
Chlamydia trachomatis. Each of these has the potential
to cause a type of pneumonia.

Causes and symptoms
Chlamydia trachomatis is a major cause of sexually transmitted diseases (called nongonococcal urethritis and pelvic inflammatory disease). When a woman
with an active chlamydial infection gives birth to a
baby, the baby may aspirate (suck into his or her
851

Chlamydial pneumonia

KEY TERMS

Chlamydial pneumonia

lungs) some of the mother’s bacteria-laden secretions
while passing through the birth canal. This can cause a
form of relatively mild pneumonia in the newborn,
occurring about two to six weeks after delivery.
Chlamydia psittaci is a bacteria carried by many
types of birds, including pigeons, canaries, parakeets,
parrots, and some gulls. Humans acquire the bacteria
through contact with dust from bird feathers, bird
droppings, or from the bite of a bird carrying the
bacteria. People who keep birds as pets or who work
where birds are kept have the highest risk for this type
of pneumonia. This pneumonia, called psittacosis,
causes fever, cough, and the production of sputum
containing pus. This type of pneumonia may be quite
severe, and is usually more serious in older patients.
The illness can last several weeks.
Chlamydia pneumoniae usually causes a type of
relatively mild ‘‘walking pneumonia.’’ Patients experience fever and cough. This type of pneumonia is called a
‘‘community-acquired pneumonia’’ because it is easily
passed from one member of the community to another.

Diagnosis
Laboratory tests indicating the presence of one of
the strains of Chlamydia are sophisticated, expensive, and
performed in only a few laboratories across the country.
For this reason, doctors diagnose most cases of chlamydial pneumonia by performing a physical examination of
the patient, and noting the presence of certain factors.
For instance, if the mother of a baby sick with pneumonia
is positive for a sexually transmitted disease caused by
Chlamydia trachomatis, the diagnosis is obvious. History
of exposure to birds in a patient sick with pneumonia
suggests that Chlamydia psittaci may be the culprit. A
mild pneumonia in an otherwise healthy person is likely
to be a community-acquired walking pneumonia, such
as that caused by Chlamydia pneumoniae.

A transmission electron microscopy (TEM) of a sectioned
Chlamydia pneumonia bacterium. (Photograph by Dr. Kari
Lounatmaa, Custom Medical Stock Photo. Reproduced by
permission.)

KEY TERMS
Alveoli—The small air sacs clustered at the ends
of the bronchioles in the lungs, in which oxygencarbon dioxide exchange takes place.
Aspiration—When solids or liquids that should be
swallowed into the stomach are instead breathed
into the respiratory system, or when substances
from the outside environment are accidentally
breathed into the lungs.
Sputum—Material produced within the alveoli in
response to an infectious or inflammatory process.

Treatment
Treatment varies depending on the specific type of
Chlamydia causing the infection. A newborn with
Chlamydia trachomatis improves rapidly with erythromycin. Chlamydia psittaci infection is treated with
tetracycline, bed rest, oxygen supplementation, and
codeine-containing cough preparations. Chlamydia
pneumoniae infection is treated with erythromycin.

Prognosis
The prognosis is generally excellent for the newborn
with Chlamydia trachomatis pneumonia. Chlamydia
852

psittaci may linger, and severe cases have a death rate
of as high as 30%. The elderly are hardest hit by this
type of pneumonia. A young, healthy person with
Chlamydia pneumoniae has an excellent prognosis. In
the elderly, however, there is a 5–10% death rate from
this infection.

Prevention
Prevention of Chlamydia trachomatis pneumonia
involves recognizing the symptoms of genital infection
GALE ENCYCLOPEDIA OF MEDICINE

inhale them. About 3,000 adults die each year from
choking on food.

Chlamydia psittaci can be prevented by warning
people who have birds as pets, or who work around
birds, to be careful to avoid contact with the dust and
droppings of these birds. Sick birds can be treated with
an antibiotic in their feed. Because people can contract
psittacosis from each other, a person sick with this
infection should be kept in isolation, so as not to infect
other people.

People also choke because infection causes the
throat tissue to swell shut. It is believed that this is
what caused George Washington’s death. Allergic
reactions can also cause the throat to swell shut.
Acute allergic reactions are called anaphylactic reactions and may be fatal. Strangulation puts external
pressure on the trachea causing another form of
choking.

Chlamydia pneumoniae is difficult to prevent
because it is spread by respiratory droplets from
other sick people. Because people with this type of
pneumonia do not always feel very sick, they often
continue to attend school, go to work, and go to
other public places. They then spread the bacteria in
the tiny droplets that are released into the air during
coughing. Therefore, this pneumonia is very difficult
to prevent and often occurs in outbreaks within
communities.

Finally, people can choke from obstructive sleep
apnea. This is a condition where tissues of the body
obstruct the airways during sleep. Sleep apnea is most
common in obese men who sleep on their backs.
Smoking, heavy alcohol use, lung diseases such as
emphysema, and an inherited tendency toward a narrowed airway and throat all increase the risk of choking during sleep.

Causes and symptoms

Resources

There are three reasons why people choke. These
are:

ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.

Rosalyn Carson-DeWitt, MD

Chlorhexidine see Antibiotics, topical
Chloroquine see Antimalarial drugs
Chlorzoxazone see Muscle relaxants

I



mechanical obstruction



tissue swelling



crushing of the trachea.

Regardless of the cause, choking cuts off the air
supply to the lungs. Indications that a person’s airway
is blocked include:


the person cannot speak or cry out



the person’s face turns blue from lack of oxygen



the person desperately grabs at his or her throat



the person has a weak cough and labored breathing
that produces a high-pitched noise



the person has all of the above symptoms, then
becomes unconscious



during sleep, the person has episodes of gasping,
pauses in breathing, and sudden awakenings.

Choking

Definition
Choking is the inability to breathe because the
trachea is blocked, constricted, or swollen shut.

Description
Choking is a medical emergency. When a person is
choking, air cannot reach the lungs. If the airways
cannot be cleared, death follows rapidly.
Anyone can choke, but choking is more common
in children than in adults. Choking is a common cause
of accidental death in young children who are apt to
put toys or coins in their mouths, then unintentionally
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Diagnosing choking due to mechanical obstruction is straightforward, since the symptoms are
obvious even to an untrained person. In choking due
to infection, the person, usually a child, will have a
fever and signs of illness before labored breathing
begins. If choking is due to an allergic reaction to
medication or insect bites, the person’s earlobes and
face will swell, giving an external sign that internal
swelling is also occurring.
853

Choking

in the mother and treating her prior to delivery of her
baby.

Cholangitis

KEY TERMS
Trachea—The windpipe. A tube extending from
below the voice box into the chest where it splits
into two branches, the bronchi, that go to each lung.
Tracheotomy—The surgical creation of an opening
in the trachea that functions as an alternative airway so that the patient may breathe.

avoiding alcohol, tobacco smoking, tranquilizers,
and sedatives before bed.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Tish Davidson, A.M.

Choking due to sleep apnea is usually diagnosed
on reports of symptoms by the person’s sleep partner.
There are also alarm devices to detect the occurrence
of sleep apnea. Eventually sleep may be interrupted so
frequently that daytime drowsiness becomes a
problem.

Treatment
Choking, except during sleep apnea, is a medical
emergency. If choking is due to allergic reaction or
infection, people should summon emergency help or
go immediately to an emergency room. If choking is
due to obstructed airways, the Heimlich maneuver (an
emergency procedure in which a person is grasped from
behind in order to forcefully expel the obstruction)
should be performed immediately. In severe cases a
tracheotomy (an incision into the trachea through the
neck below the larynx) must be performed.
Patients who suffer airway obstruction during
sleep can be treated with a device similar to an oxygen
mask that creates positive airway pressure and delivers
a mixture of oxygen and air.

Prognosis
Many people are treated successfully for choking
with no permanent effects. However, if treatment is
unsuccessful, the person dies from lack of oxygen. In
cases where the airway is restored after the critical
period passes, there may be permanent brain damage.

Prevention
Watching children carefully to keep them from
putting foreign objects in their mouth and avoiding
giving young children food like raisins, round slices
of hot dogs, and grapes can reduce the chance of
choking in children. Adults should avoid heavy alcohol consumption when eating and avoid talking and
laughing with food in their mouths. The risk of
obstructive sleep apnea choking can be reduced by
854

I Cholangitis
Definition
The term cholangitis means inflammation of the
bile ducts. The term applies to inflammation of any
portion of the bile ducts, which carry bile from the
liver to the gallbladder and intestine. The inflammation is produced by bacterial infection or sometimes
other causes.

Description
Bile, which is needed for digestion, is produced in
the liver and then enters the common bile duct (CBD)
through the hepatic ducts. Bile enters the gallbladder
between meals, when the muscle or sphincter that
controls flow of bile between the CBD and intestine
is closed. During this period, bile accumulates in the
CBD; the pressure in the CBD rises, as would a pipe
closed off at one end. The increase in pressure eventually causes the bile to flow into the gallbladder.
During meals, the gallbladder contracts and the
sphincter between the gallbladder and intestine
relaxes, permitting bile to flow into the intestine and
take part in digestion.
Bile that has just been produced by the liver is
sterile (free of bacteria). This is partly due to its antibacterial properties; these are produced by the immunoglobulins (antibodies) secreted in bile, the bile acids
which inhibit bacterial growth themselves, and mucus.
A small number of bacteria may be present in the
bile ducts and gallbladder, getting there by moving
backward from the intestine, which unlike the bile
ducts, contains large numbers of bacteria. The normal
flow of bile out of the ducts and into the intestine also
helps keep too many organisms from multiplying.
Bacteria also reach the bile ducts from the lymph
tissue or from the blood stream.
GALE ENCYCLOPEDIA OF MEDICINE

Another source of inflammation of the bile ducts
occurs in diseases of altered immunity, known as
‘‘autoimmune diseases.’’ In these diseases, the body
fails to recognize certain cells as part of its normal
composition. The body thinks these cells are foreign
and produces antibodies to fight them off, just as it
fights against bacteria and viruses. Primary sclerosing
cholangitis is a typical example of an autoimmune
disease involving the bile ducts.

Causes and symptoms
As noted above, the two things that are needed for
cholangitis to occur are: 1) obstruction to bile flow,
and 2) presence of bacteria within the bile ducts. The
most common cause of cholangitis is infection of the
bile ducts due to blockage by a gallstone. Strictures
(portions of ducts that have become narrow) also
function in the same way. Strictures may be due to
congenital (birth) abnormalities of the bile ducts, form
as a result of injury to the bile duct (such as surgery,
trauma), or result from inflammation that leads to
scar tissue and narrowing.
The bacterium most commonly associated with
infection of the bile ducts is Escherichia coli (E. coli)
which is a normal inhabitant of the intestine. In
some cases, more than one type of bacteria is involved.
Patients with AIDS can develop infection of narrowed bile ducts with unusual organisms such as
Cryptosporidium and others.
The three symptoms present in about 70% of
patients with cholangitis are abdominal pain, fever,
and jaundice. Some patients only have chills and
fever with minimal abdominal symptoms. Jaundice
or yellow discoloration of the skin and eyes occurs in
about 80% of patients. The color change is due to bile
pigments that accumulate in the blood and eventually
in the skin and eyes.
Inflammation due to the autoimmune disease primary sclerosing cholangitis leads to multiple areas of
narrowing and eventual infection. Tumors can block
GALE ENCYCLOPEDIA OF MEDICINE

the bile duct and also cause cholangitis, but as noted,
infection is relatively infrequent; in fact cholangitis
occurs in only about one in six patients with tumors.
Another type of bile duct infection occurs mainly
in Southeast Asia and is known as recurrent pyogenic
cholangitis or Oriental cholangitis. It has also been
identified in Asians immigrating to North America.
Most patients have stones in the bile ducts and/or
gallbladder, and many cases are associated with the
presence of parasites within the ducts. The role of
parasites in causing infection is not clear. Many
researchers believe that they are just coincidental,
and have nothing to do with the stones or infection.

Diagnosis
The above symptoms alone are very suggestive of
cholangitis; however, it is important to determine the
exact cause and site of possible obstruction. This is
because attacks are likely to recur, and different causes
require different treatments. For example, the treatment of cholangitis due to a stone in the CBD is
different from that due to bile duct strictures. An
elevated white blood count suggests infection, but
may be normal in 20% of patients. Abnormal or elevated tests of liver function, such as bilirubin and
others are also frequently present. The specific
bacteria is sometimes identified from blood cultures.
X-ray techniques
A number of x-ray techniques can make the diagnosis of bile duct obstruction; these include ultrasound
and computed tomography scans (CT scans). However,
ultrasound often cannot tell if an obstruction is due to
a stricture or stone, missing a stone in about half the
cases. CT scans have an even poorer record of stone
detection.
Another method of diagnosing and sometimes
treating the cause of bile duct obstruction or narrowing is called percutaneous transhepatic cholangiography. In this procedure, dye is injected into the ducts
by means of a needle placed into the liver. It is also
used to drain bile and relieve an obstruction.
ENDOSCOPIC TECHNIQUES. An endoscope is a thin
flexible tube that uses a lens or mirror to look at
various parts of the gastrointestinal tract. Endoscopic
retrograde cholangiopancreatography (ERCP) can
accurately determine the cause and site of blockage.
It also has the advantage of being able to treat the
cause of obstruction, by removing stones and dilating
(stretching) strictures. ERCP involves the injection of
x-ray dye into the bile ducts through an endoscope.

855

Cholangitis

When the passage of bile out of the ducts is
blocked, the few bacteria that are there rapidly reproduce. A partial blockage to the flow of bile can occur
when a stone from the gallbladder blocks the duct, and
also allows bacteria to flow back into the CBD, and
creates ideal conditions for their growth. Tumors, on
the other hand, cause a more complete blockage of bile
flow, both in and out, so fewer infections occur. The
reproducing organisms are often able to enter the
bloodstream and infect multiple organs such as
the liver and heart valves.

Cholangitis

Endoscopic ultrasound is another endoscopic alternative, but is not as available as ERCP and is not
therapeutic.

Treatment
The first aim is to control the bacterial infection.
Broad-spectrum antibiotics are usually used. If the
infection does not come under control promptly, as
noted by decrease in fever and pain, then other methods to relieve the obstruction and infection will be
needed. Either way, definitive treatment of the cause
of bile duct infection is the next step, and this has
undergone revolutionary changes in the past decade.
Endoscopic, radiographic and other techniques have
made it possible to successfully remove stones and
dilate strictures that previously required surgical intervention, often with high morbidity and mortality.
Radiologic and endoscopic techniques
Just as with diagnosis, treatment of cholangitis
involves a number of similar procedures that differ
mainly in the way the bile ducts are entered. The
aims of these techniques are immediate relief of
obstruction and infection as well as correction of any
abnormalities that have caused them. It is important
to realize that even with endoscopy, x-ray dye is
injected into the ducts and therefore the radiologist
plays a role in both types of procedures. When endoscopy is used, the muscle between the intestine and bile
duct is widened, to allow stones to pass. This is called a
sphincterotomy and is often enough to relieve any
obstruction and help clear infection. The widening of
the muscle is needed if other procedures involving the
bile duct are going to be performed.
The above techniques can be summarized as
follows:


Insertion of a catheter or thin flexible tube to drain
bile and relieve obstruction. When performed by
insertion of a needle into the liver the technique is
called percutaneous transhepatic biliary drainage
(PTBD); when performed endoscopically the catheter exits through the nose and is called a nasobiliary
drain.



Balloons can be inserted into the ducts with either
method to dilate strictures.



Insertion of a prosthesis which is a rigid or flexible
tube designed to keep a narrowed area open; it is
usually placed after a stricture is dilated with a
balloon.



Removal of stones can be accomplished most often
by endoscopic techniques. A number of methods

856

have been developed to perform this including laser
and contact lithotripsy in which stones are fragmented by high-energy waves.
Surgical treatment
Fortunately, with recent advances in the above
methods, this is a last option. Nonetheless, about
5–10% of patients will need to undergo surgical
exploration of the bile ducts.
In some instances, the bile duct is so narrowed due
to prior inflammation or tumor, that it needs connection to a different area of the intestinal tract to drain.
This is rather complicated surgery and carries a mortality rate of 2%.
Other treatment
Extracorporeal shock-wave lithotripsy (ESWL)
was first used to break up kidney stones. The technique
has been extended to the treatment of gallstones, in
both the gallbladder and bile ducts. It is often combined with endoscopic procedures to ease the passage
of fragmented stones, or oral medications that can
dissolve the fragments. Rarely, stones are also dissolved by instilling various chemicals such as ether
directly into the bile ducts.

Prognosis
The outlook for those with cholangitis has markedly improved in the last several years due in large part
to the development of the techniques described above.
For those patients whose episode of infection is caused
by something other than a simple stone, the future is
not as bright, but still often responsive to treatment.
Some patients with autoimmune disease will need liver
transplantation.

Prevention
This involves eliminating those factors that
increase the risk of infection of the bile ducts, mainly
stones and strictures. If it is medically possible,
patients who have their gallbladder and suffer a bout
of cholangitis should undergo surgical removal of the
gallbladder and removal of any stones.
For other patients, a variety of therapies as outlined above, including dissolving small stones with bile
acids are also available. A combination of several of
these methods is needed in some patients. Patients
should discuss the risks and alternatives of these treatments with their physicians.
GALE ENCYCLOPEDIA OF MEDICINE

Antibiotic—A medication that is designed to kill or
weaken bacteria.
Bilirubin—A pigment produced by the liver that is
excreted in bile which causes a yellow discoloration
of the skin and eyes when it accumulates in those
organs. Bilirubin levels can be measured by blood
tests, and are most often elevated in patients with
liver disease or a blockage to bile flow.
Computed tomography scan (CT scan)—A specialized x-ray procedure in which cross-sections of the
area in question can be examined in detail. In evaluating the bile ducts, iodine-based dye is often
injected intravenously. The procedure is of greatest
value in diagnosing the complications of gallstones
(such as abscesses, pancreatitis) rather than documenting the presence of a stone.
Endoscope—An endoscope as used in the field of
gastroenterology is a thin flexible tube which uses a
lens or miniature camera to view various areas of the
gastrointestinal tract. When the procedure is performed to examine certain organs such as the bile
ducts or pancreas, the organs are not viewed
directly, but rather indirectly through the injection
of x-ray dye into the bile duct.
Endoscopy—The performance of an exam using an
endoscope is referred by the general term endoscopy.
Diagnosis through biopsies or other means and therapeutic procedures can be done with these instruments.

Resources
OTHER

‘‘Endoscopic Retrograde Cholangiopancreatography
(ERCP).’’ American Society for Gastrointestinal
Endoscopy. <http://www.asge.org>.
‘‘Gallstones.’’ National Institute of Diabetes and Digestive
and Kidney Disease. <http://www.niddk.nih.gov>.
Kaminstein, David S. ‘‘Gallstones.’’ A Healthy Me Page.
<http://www.ahealthyme.com/topic/cholangitis>.
‘‘Primary Sclerosing Cholangitis.’’ National Institute of
Diabetes and Digestive and Kidney Disease. <http://
www.niddk.nih.gov>.
Worman, Howard J. ‘‘Sclerosing Cholangitis.’’ Columbia
University Health Sciences Page. <http://cpmcnet.
columbia.edu/dept/gi/PSC.html>.
‘‘Your Digestive System and How It Works.’’ National
Institute of Diabetes and Digestive and Kidney Disease.
<http://www.niddk.nih.gov>.

David Kaminstein, MD
GALE ENCYCLOPEDIA OF MEDICINE

Extracorporeal shock-wave lithotripsy (ESWL)—
This is a technique that uses high-pressure waves
similar to sound waves that can be ‘‘focused’’ on a
very small area, thereby fracturing small solid objects
such as gallstones, kidney stones, etc. The small fragments can pass more easily and harmlessly into the
intestine or can be dissolved with medications.
Primary sclerosing cholangitis—A chronic disease
in which it is believed that the immune system fails
to recognize the cells that compose the bile ducts as
part of the same body, and attempts to destroy them.
It is not clear what exactly causes the disease, but it is
frequently associated with another inflammatory
disease of the digestive tract, ulcerative colitis. The
inflammation of the ducts eventually produces formation of scar tissue, causing multiple areas of narrowing (strictures) that block bile flow and lead to
bacterial infection. Liver transplant gives the best
chance for long-term survival.
Ultrasound—A non-invasive procedure based on
changes in sound waves of a frequency that cannot
be heard, but respond to changes in tissue composition. It requires no preparation and no radiation
occurs. It has become the ‘‘gold standard’’ for diagnosis of stones in the gallbladder, but is less accurate
in diagnosing stones in the bile ducts. Gallstones as
small as 2 mm can be identified. The procedure can
now also be done through an endoscope, greatly
improving investigation of the bile ducts.

I Cholecystectomy
Definition
A cholecystectomy is the surgical removal of the
gallbladder. The two basic types of this procedure are
open cholecystectomy and the laparoscopic approach.
It is estimated that the laparoscopic procedure is currently used for approximately 80% of cases.

Purpose
A cholecystectomy is performed to treat cholelithiasis and cholecystitis. In cholelithiasis, gallstones
of varying shapes and sizes form from the solid components of bile. The presence of stones, often referred
to as gallbladder disease, may produce symptoms of
excruciating right upper abdominal pain radiating to
the right shoulder. The gallbladder may become the
857

Cholecystectomy

KEY TERMS

Cholecystectomy

KEY TERMS

A surgeon performs a laparoscoptic cholecystectomy on a
patient. (Custom Medical Stock Photo. Reproduced by
permission.)

site of acute infection and inflammation, resulting in
symptoms of upper right abdominal pain, nausea and
vomiting. This condition is referred to as cholecystitis. The surgical removal of the gallbladder can
provide relief of these symptoms.

Precautions
Although the laparoscopic procedure requires
general anesthesia for about the same length of time
as the open procedure, laparoscopy generally produces
less postoperative pain, and a shorter recovery period.
The laparoscopic procedure would not be preferred in
cases where the gallbladder is so inflamed that it could
rupture, or when adhesions (additional fibrous bands
of tissue) are present.

Description
The laparoscopic cholecystectomy involves the
insertion of a long narrow cylindrical tube with a
camera on the end, through an approximately 1 cm
incision in the abdomen, which allows visualization of
the internal organs and projection of this image onto a
video monitor. Three smaller incisions allow for insertion of other instruments to perform the surgical procedure. A laser may be used for the incision and
cautery (burning unwanted tissue to stop bleeding),
in which case the procedure may be called laser laparoscopic cholecystectomy.
In a conventional or open cholecystectomy, the
gallbladder is removed through a surgical incision
high in the right abdomen, just beneath the ribs.
A drain may be inserted to prevent accumulation of
fluid at the surgical site.
858

Cholecystitis—Infection and inflammation of the
gallbladder, causing severe pain and rigidity in the
upper right abdomen.
Cholelithiasis—Also known as gallstones, these
hard masses are formed in the gallbladder or passages, and can cause severe upper right abdominal
pain radiating to the right shoulder, as a result of
blocked bile flow.
Gallbladder—A hollow pear-shaped sac on the
under surface of the right lobe of the liver. Bile
comes to it from the liver, and passes from it to
the intestine to aid in digestion.

Preparation
As with any surgical procedure, the patient will be
required to sign a consent form after the procedure is
explained thoroughly. Food and fluids will be prohibited after midnight before the procedure. Enemas may
be ordered to clean out the bowel. If nausea or vomiting
are present, a suction tube to empty the stomach may be
used, and for laparoscopic procedures, a urinary drainage catheter will also be used to decrease the risk of
accidental puncture of the stomach or bladder with
insertion of the trocar (a sharp-pointed instrument).

Aftercare
Post-operative care for the patient who has had an
open cholecystectomy, as with those who have had
any major surgery, involves monitoring of blood pressure, pulse, respiration and temperature. Breathing
tends to be shallow because of the effect of anesthesia,
and the patient’s reluctance to breathe deeply due to
the pain caused by the proximity of the incision to the
muscles used for respiration. The patient is shown how
to support the operative site when breathing deeply
and coughing, and given pain medication as necessary.
Fluid intake and output is measured, and the operative site is observed for color and amount of wound
drainage. Fluids are given intravenously for 24–48
hours, until the patient’s diet is gradually advanced
as bowel activity resumes. The patient is generally
encouraged to walk 8 hours after surgery and discharged from the hospital within three to five days,
with return to work approximately four to six weeks
after the procedure.
Care received immediately after laparoscopic
cholecystectomy is similar to that of any patient
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Potential problems associated with open cholecystectomy include respiratory problems related to location of the incision, wound infection, or abscess
formation. Possible complications of laparoscopic cholecystectomy include accidental puncture of the bowel
or bladder and uncontrolled bleeding. Incomplete reabsorption of the carbon dioxide gas could irritate the
muscles used in respiration and cause respiratory
distress.
Resources
OTHER

‘‘Gallstones and Laparoscopic Cholecystectomy.’’ Centers
for Disease Control and Prevention. <http://
www.cdc.gov/nccdphp/ddt/ddthome.htm>.
‘‘Patient Information Documents on Digestive Diseases.’’
National Institute of Diabetes and Digestive and Kidney
Disease. <http://www.niddk.nih.gov>.

Kathleen D. Wright, RN

I Cholecystitis
Definition
Cholecystitis refers to a painful inflammation of
the gallbladder’s wall. The disorder can occur a single
time (acute), or can recur multiple times (chronic).

Description
The gallbladder is a small, pear-shaped organ in
the upper right hand corner of the abdomen. It is
connected by a series of ducts (tube-like channels) to
the liver, pancreas, and duodenum (first part of the
small intestine). To aid in digestion, the liver produces
GALE ENCYCLOPEDIA OF MEDICINE

a substance called bile, which is passed into the gallbladder. The gallbladder concentrates this bile, meaning that it reabsorbs some of the fluid from the bile to
make it more potent. After a meal, bile is squeezed out
of the gallbladder by strong muscular contractions,
and passes through a duct into the duodenum. Due
to the chemical makeup of bile, the contents of the
duodenum are kept at an optimal pH level for digestion. The bile also plays an important part in allowing
fats within the small intestine to be absorbed.

Causes and symptoms
In about 95% of all cases of cholecystitis, the
gallbladder contains gallstones. Gallstones are solid
accumulations of the components of bile, particularly
cholesterol, bile pigments, and calcium. These solids
may occur when the components of bile are not in the
correct proportion to each other. If the bile becomes
overly concentrated, or if too much of one component
is present, stones may form. When these stones block
the duct leaving the gallbladder, bile accumulates
within the gallbladder. The gallbladder continues to
contract, but the bile cannot pass out of the gallbladder in the normal way. Back pressure on the gallbladder, chemical changes from the stagnating bile trapped
within the gallbladder, and occasionally bacterial
infection, result in damage to the gallbladder wall.
As the gallbladder becomes swollen, some areas of
the wall do not receive adequate blood flow, and lack
of oxygen causes cells to die.
When the stone blocks the flow of bile from the
liver, certain normal byproducts of the liver’s processing of red blood cells (called bilirubin) build up. The
bilirubin is reabsorbed into the bloodstream, and over
time this bilirubin is deposited in the skin and in the
whites of the eyes. Because bilirubin contains a yellowish color, it causes a yellowish cast to the skin and eyes
that is called jaundice.
Gallstone formation is seen in twice as many
women as men, particularly those between the ages of
20 and 60. Pregnant women, or those on birth control
pills or estrogen replacement therapy have a greater risk
of gallstones, as do Native Americans and Mexican
Americans. People who are overweight, or who lose a
large amount of weight quickly are also at greater risk
for developing gallstones. Not all individuals with gallstones will go on to have cholecystitis, since many
people never have any symptoms from their gallstones
and never know they exist. However, the vast majority
of people with cholecystitis will be found to have gallstones. Rare causes of cholecystitis include severe burns
or injury, massive systemic infection, severe illness,
859

Cholecystitis

undergoing surgery with general anesthesia. A unique
post-operative pain may be experienced in the right
shoulder related to pressure from carbon dioxide used
through the laparoscopic tubes. This pain may be
relieved by laying on the left side with right knee and
thigh drawn up to the chest. Walking will also help
increase the body’s reabsorption of the gas. The patient
is usually discharged the day after surgery, and allowed
to shower on the second postoperative day. The patient
is advised to gradually resume normal activities over a
three day period, while avoiding heavy lifting for about
10 days.

Cholecystitis

diabetes, obstruction by a tumor of the duct leaving the
gallbladder, and certain uncommon infections of the
gallbladder (including bacteria and worms).
Although there are rare reports of patients with
chronic cholecystitis who never experience any pain,
nearly 100% of the time cholecystitis will be diagnosed
after a patient has experienced a bout of severe pain in
the region of the gallbladder and liver. The pain may
be crampy and episodic, or it may be constant. The
pain is often described as pushing through to the right
upper back and shoulder. Because deep breathing
increases the pain, breathing becomes shallow. Fever
is often present, and nausea and vomiting are nearly
universal. Jaundice occurs when the duct leaving the
liver is also obstructed, although it may take a number
of days for it to become apparent. When bacterial
infection sets in, the patient may begin to experience
higher fever and shaking chills.

A close-up view of an inflamed gallbladder. (Custom Medical
Stock Photo. Reproduced by permission.)

in stretching of the gallbladder and disruption of its
wall by gas.

Diagnosis
Diagnosis of cholecystitis involves a careful
abdominal examination. The enlarged, tender gallbladder may be felt through the abdominal wall.
Pressure in the upper right corner of the abdomen
may cause the patient to stop breathing in, due to an
increase in pain. This is called Murphy’s sign. Physical
examination may also reveal an increased heart rate
and an increased rate of breathing.
Blood tests will show an increase in the white
blood count, as well as an increase in bilirubin.
Ultrasound is used to look for gallstones and to measure the thickness of the gallbladder wall (a marker of
inflammation and scarring). A scan of the liver and
gallbladder, with careful attention to the system of
ducts throughout (called the biliary tree) is also used
to demonstrate obstruction of ducts.
Rare complications of cholecystitis include:


massive infection of the gallbladder, in which the
gallbladder becomes filled with pus (called empyema)



perforation of the gallbladder, in which the build-up
of material within the gallbladder becomes so great
that the wall of the organ bursts, with a resulting
abdominal infection called peritonitis



formation of abnormal connections between the gallbladder and other organs (the duodenum, large intestine, stomach), called fistulas



obstruction of the intestine by a very large gallstone
(called gallstone ileus)



emphysema of the gallbladder, in which certain bacteria that produce gas infect the gallbladder, resulting

860

Treatment
Initial treatment of cholecystitis usually requires
hospitalization. The patient is given fluids, salts, and
sugars through a needle placed in a vein (intravenous
or IV). No food or drink is given by mouth, and often
a tube, called a nasogastric or NG tube, will need to be
passed through the nose and down into the stomach to
drain out the excess fluids. If infection is suspected,
antibiotics are given.
Ultimately, treatment almost always involves
removal of the gallbladder, a surgery called cholecystectomy. While this is not usually recommended while
the patient is acutely ill, patients with complications
usually do require emergency surgery (immediately
following diagnosis) because the death rate increases
in these cases. Similarly, those patients who have cholecystitis with no gallstones have about a 50% chance
of death if the gallbladder is not quickly removed.
Most patients, however, do best if surgery is performed after they have been stabilized with fluids, an
NG tube, and antibiotics as necessary. When this is
possible, gallbladder removal is done within five to six
days of diagnosis. In patients who have other serious
medical problems that may increase the risks of gallbladder removal surgery, the surgeon may decide to
leave the gallbladder in place. In this case, the operation may involve removing obstructing gallstones and
draining infected bile (called cholecystotomy).
Both cholecystectomy and cholecystotomy may
be performed via the classical open abdominal operation (laparotomy). Tiny, ‘‘keyhole’’ incisions, a flexible scope, and a laser device that shatters the stones
GALE ENCYCLOPEDIA OF MEDICINE

Bile—A substance produced by the liver, and concentrated and stored in the gallbladder. Bile contains many different substances, including bile
salts, cholesterol, and bilirubin. After a meal, the
gallbladder pumps bile into the duodenum (the first
part of the small intestine) to keep the intestine’s
contents at the appropriate pH for digestion, and to
help break down fats.
Bilirubin—Produced when red blood cells break
down. It is a yellowish color and when levels are
abnormally high, it causes the yellowish tint to eyes
and skin known as jaundice.
Cholecystectomy—An operation to remove the
gallbladder.
Cholecystotomy—An operation during which the
gallbladder is opened, gallstones are removed, and
excess bile is drained. The gallbladder is not removed.
Duct—A tube through which various substances
can pass. These substances can travel through
ducts to another organ or into the bloodstream.

ORGANIZATIONS

Digestive Disease National Coalition. 507 Capitol Court
NE, Suite 200, Washington, DC 20003. (202) 544-7497.
<http://www.ddnc.org>.
National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.

Rosalyn Carson-DeWitt, MD

Cholecystography see Gallbladder x rays
Choledocholithiasis see Gallstones
Cholelithiasis see Gallstones
Cholelithotomy see Gallstone removal

I Cholera
Definition

(a laparoscopic laser) can be used to destroy the gallstones. The laparoscopic procedure can also be used to
remove the gallbladder through one of the small incisions. Because of the smaller incisions, laparoscopic
cholecystectomy is a procedure that is less painful and
promotes faster healing.

Prognosis
Hospital management of cholecystitis ends the
symptoms for about 75% of all patients. Of these
patients, however, 25% will go on to have another
attack of cholecystitis within a year, and 60% will
have another attack within six years. Each attack of
cholecystitis increases a patient’s risk of developing
life-threatening complications, requiring risky emergency surgery. Therefore, early removal of the gallbladder, rather than a ‘‘wait-and-see’’ approach, is
usually recommended. Cure is complete in those
patients who undergo cholecystectomy.

Prevention
Prevention of cholecystitis is probably best
attempted by maintaining a reasonably ideal weight.
Some studies have suggested that eating a diet high in
fiber, vegetables, and fruit is also protective.
GALE ENCYCLOPEDIA OF MEDICINE

Cholera is an acute infectious disease characterized by watery diarrhea that is caused by the bacterium
Vibrio cholerae, first identified by Robert Koch in
1883 during a cholera outbreak in Egypt. The name
of the disease comes from a Greek word meaning
‘‘flow of bile.’’
Cholera is spread by eating food or drinking
water contaminated with the bacterium. Although
cholera was a public health problem in the United
States and Europe a hundred years ago, modern
sanitation and the treatment of drinking water have
virtually eliminated the disease in developed countries. Cholera outbreaks, however, still occur from
time to time in less developed countries, particularly
following such natural disasters as the tsunami that
struck countries surrounding the Indian Ocean in
December 2004. In these areas cholera is still the
most feared epidemic diarrheal disease because people
can die within hours of infection from dehydration
due to the loss of water from the body through the
bowels.
V. cholerae is a gram-negative aerobic bacillus, or
rod-shaped bacterium. It has two major biotypes:
classic and El Tor. El Tor is the biotype responsible
for most of the cholera outbreaks reported from 1961
through the early 2000s.
861

Cholera

Resources

KEY TERMS

Cholera

Description
Cholera is spread by eating food or drinking water
that has been contaminated with cholera bacteria.
Contamination usually occurs when human feces
from a person who has the disease seeps into a community water supply. Fruits and vegetables can also be
contaminated in areas where crops are fertilized with
human feces. Cholera bacteria also live in warm, brackish water and can infect persons who eat raw or undercooked seafood obtained from such waters. Cholera is
rarely transmitted directly from one person to another.
Cholera often occurs in outbreaks or epidemics;
seven pandemics (countrywide or worldwide epidemics)
of cholera have been recorded between 1817 and 2003.
The World Health Organization (WHO) estimates that
during any cholera epidemic, approximately 0.2–1% of
the local population will contract the disease. Anyone
can get cholera, but infants, children, and the elderly are
more likely to die from the disease because they become
dehydrated faster than adults. There is no particular
season in which cholera is more likely to occur.
Because of an extensive system of sewage and water
treatment in the United States, Canada, Europe, Japan,
and Australia, cholera is generally not a concern for
visitors and residents of these countries. Between 1995
and 2000, 61 cases of cholera in American citizens were
reported to the Centers for Disease Control and
Prevention (CDC); only 24 represented infections
acquired in the United States. People visiting or living
in other parts of the world, particularly on the Indian
subcontinent and in parts of Africa and South America,
should be aware of the potential for contracting cholera
and practice prevention. Fortunately, the disease is
both preventable and treatable.

Causes and symptoms
Because V. cholerae is sensitive to acid, most choleracausing bacteria die in the acidic environment of the
stomach. However, when a person has ingested food or
water containing large amounts of cholera bacteria, some
will survive to infect the intestines. As would be
expected, antacid usage or the use of any medication
that blocks acid production in the stomach would allow
more bacteria to survive and cause infection.
In the small intestine, the rapidly multiplying
bacteria produce a toxin that causes a large volume of
water and electrolytes to be secreted into the bowels and
then to be abruptly eliminated in the form of watery
diarrhea. Vomiting may also occur. Symptoms begin to
appear between one and three days after the contaminated food or water has been ingested.
862

A false color transmission electron micrograph (TEM) of
Vibrio cholerae bacterium magnified 6,000 times its original
size. (Photography by T. McCarthy, Custom Medical Stock
Photo. Reproduced by permission.)

Most cases of cholera are mild, but about one in 20
patients experience severe, potentially life-threatening
symptoms. In severe cases, fluids can be lost through
diarrhea and vomiting at the rate of one quart per hour.
This can produce a dangerous state of dehydration
unless the lost fluids and electrolytes are rapidly
replaced.
Signs of dehydration include intense thirst, little
or no urine output, dry skin and mouth, an absence of
tears, glassy or sunken eyes, muscle cramps, weakness,
and rapid heart rate. The fontanelle (soft spot on an
infant’s head) will appear to be sunken or drawn in.
Dehydration occurs most rapidly in the very young
and the very old because they have fewer fluid
reserves. A doctor should be consulted immediately
any time signs of severe dehydration occur. Immediate
replacement of the lost fluids and electrolytes is necessary to prevent kidney failure, coma, and death.
Some people are at greater risk of having a severe
case of cholera if they become infected:


People taking proton pump inhibitors, histamine
blockers, or antacids to control acid indigestion. As
noted earlier, V. cholerae is sensitive to stomach acid.



People who have had chronic gastritis caused by
infection with Helicobacter pylori.



People who have had a partial gastrectomy (surgical
removal of a portion of the stomach).

Diagnosis
Rapid diagnosis of cholera can be made by examining a fresh stool sample under the microscope for the
GALE ENCYCLOPEDIA OF MEDICINE

their feces for up to two weeks. Chronic carriers of
the disease are rare. With prompt fluid and electrolyte replacement, the death rate in patients with
severe cholera is less than 1%. Untreated, the death
rate can be greater than 50%. The difficulty in treating severe cholera does not lie in not knowing how to
treat it but rather in getting medical care to the sick in
underdeveloped areas of the world where medical
resources are limited.

Treatment
The key to treating cholera lies in preventing dehydration by replacing the fluids and electrolytes lost
through diarrhea and vomiting. The discovery that
rehydration can be accomplished orally revolutionized
the treatment of cholera and other, similar diseases by
making this simple, cost-effective treatment widely
available throughout the world. The World Health
Organization has developed an inexpensive oral replacement fluid containing appropriate amounts of water,
sugar, and salts that is used worldwide. In cases of severe
dehydration, replacement fluids must be given intravenously. Patients should be encouraged to drink when
they can keep liquids down and eat when their appetite
returns. Recovery generally takes three to six days.
Adults may be given the antibiotic tetracycline to
shorten the duration of the illness and reduce fluid loss.
The World Health Organization recommends this antibiotic treatment only in cases of severe dehydration. If
antibiotics are overused, the cholera bacteria organism
may become resistant to the drug, making the antibiotic
ineffective in treating even severe cases of cholera.
Tetracycline is not given to children whose permanent
teeth have not come in because it can cause the teeth to
become permanently discolored.
Other antibiotics that may be given to speed up
the clearance of V. cholerae from the body include
ciprofloxacin and erythromycin.
A possible complementary or alternative treatment for fluid loss caused by cholera is a plant-derived
compound, an extract made from the tree bark of
Croton lechleri, the Sangre de grado tree found in the
South American rain forest. Researchers at a hospital
research institute in California report that the extract
appears to work by preventing the loss of chloride and
other electrolytes from the body.

Prognosis
Today, cholera is a very treatable disease.
Patients with milder cases of cholera usually recover
on their own in three to six days without additional
complications. They may eliminate the bacteria in
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
The best form of cholera prevention is to establish
good sanitation and waste treatment systems. In the
absence of adequate sewage treatment, the following
guidelines should be followed to reduce the possibility
of infection:


Boil it. Drink and brush teeth only with water that
has been boiled or treated with chlorine or iodine
tablets. Safe drinks include coffee and tea made
with boiling water or carbonated bottled water and
carbonated soft drinks.



Cook it. Eat only thoroughly cooked foods, and eat
them while they are still hot. Avoid eating food from
street vendors.



Peel it. Eat only fruit or nuts with a thick intact skin
or shell that is removed immediately before eating.



Forget it. Do not eat raw foods such as oysters or
ceviche. Avoid salads and raw vegetables. Do not use
untreated ice cubes in otherwise safe drinks.



Stay out of it. Do not swim or fish in polluted water.

Preventive measures following natural disasters
include guaranteeing the purity of community drinking water, either by large-scale chlorination and boiling, or by bringing in bottled or purified water from
the outside. Other important preventive measures at
the community level include provision for the safe
disposal of human feces and good food hygiene.
Because cholera is one of the few infectious diseases that can be spread by human remains (through
fecal matter leaking from corpses into the water supply), emergency workers who handle human remains
are at increased risk of infection. It is considered preferable to bury corpses rather than to cremate them,
however, and to allow survivors time to conduct
appropriate burial ceremonies or rituals. The remains
should be disinfected prior to burial, and buried at
least 90 feet (30 m) away from sources of drinking
water.
A cholera vaccine exists that can be given to travelers and residents of areas where cholera is known to be
863

Cholera

presence of V. cholerae bacteria. Cholera can also be
diagnosed by culturing a stool sample in the laboratory to isolate the cholera-causing bacteria. In addition, a blood test may reveal the presence of antibodies
against the cholera bacteria. In areas where cholera
occurs often, however, patients are usually treated for
diarrhea and vomiting symptoms as if they had cholera without laboratory confirmation.

Cholestasis

KEY TERMS
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Bacillus—A rod-shaped bacterium. The organism
that causes cholera is a gram-negative bacillus.
Biotype—A variant strain of a bacterial species
with distinctive physiological characteristics.
Electrolytes—Salts and minerals that ionize in body
fluids. Common human electrolytes are sodium,
chloride, potassium, and calcium. Electrolytes control the fluid balance of the body and are important
in muscle contraction, energy generation, and
almost all major biochemical reactions in the body.
Pandemic—A widespread epidemic that affects
whole countries or the entire world. There have
been seven cholera pandemics since 1817.
Toxin—A poison. In the case of cholera, a poison
secreted as a byproduct of the growth of the
cholera bacteria in the small intestine.

active, but the vaccine is not highly effective. It provides
only 25–50% immunity, and then only for a period of
about six months. The vaccine is never given to infants
under six months of age. The Centers for Disease
Control and Prevention do not currently recommend
cholera vaccination for travelers. Residents of choleraplagued areas should discuss the value of the vaccine
with their doctor.
A newer cholera vaccine known as Peru-15 underwent phase II trials in the summer of 2003. As of mid2004, the manufacturer is planning phase III trials in a
developing country and in travelers. Peru-15 is classified as a single-dose recombinant vaccine.

Secretion in Human Colonic Epithelial Cells.’’ Journal
of Ethnopharmacology 93 (August 2004): 351–357.
Handa, Sajeev. ‘‘Cholera.’’ eMedicine. [cited March 21,
2003]. <http://www.emedicine.com/med/
topic351.htm>.
Jones, T. ‘‘Peru-15 (AVANT).’’ Current Opinion in
Investigational Drugs 5 (August 2004): 887–891.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
Infectious Diseases Society of America (IDSA). 66 Canal
Center Plaza, Suite 600, Alexandria, VA 22314. (703)
299-0200. Fax: (703) 299-0204. <http://
www.idsociety.org>.
World Health Organization (WHO). <http://
www.who.int/en/>.
OTHER

World Health Organization Fact Sheet. ‘‘Cholera.’’ Fact
sheet No. 107, March 2000. <http://www.who.int/
mediacentre/factsheets/fs107/en/>.
World Health Organization Fact Sheet. ‘‘Flooding and
Communicable Diseases Fact Sheet: Risk Assessment
and Preventive Measures.’’ December 2004. <http://
www.who.int/hac/techguidance/ems/flood_cds/en/
index.html>.

Tish Davidson, A.M.
Rebecca J. Frey, PhD

I Cholestasis
Definition
Cholestasis is a condition caused by rapidly developing (acute) or long-term (chronic) interruption in
the excretion of bile (a digestive fluid that helps the
body process fat). The term is taken from the Greek
chole, bile, and stasis, standing still.

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Bacterial Diseases.’’ Section 13, Chapter 157. In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2002.
PERIODICALS

Altman, Lawrence K., MD, and Denise Grady. ‘‘Water Is
Key to Averting Epidemics Along Coasts.’’ New York
Times December 30, 2004.
Fischer, H., T. E. Machen, J. H. Widdicombe, et al.
‘‘A Novel Extract SB-300 from the Stem Bark Latex of
Croton lechleri Inhibits CFTR-Mediated Chloride
864

Description
Cholestasis is caused by obstruction within the
liver (intrahepatic) or outside the liver (extrahepatic).
The obstruction causes bile salts, the bile pigment
bilirubin, and fats (lipids) to accumulate in the blood
stream instead of being eliminated normally.
Intrahepatic cholestasis is characterized by widespread blockage of small ducts or by disorders, such as
hepatitis, that impair the body’s ability to eliminate bile.
Extrahepatic cholestasis can occur as a side effect of
many medications. It can also occur as a complication
GALE ENCYCLOPEDIA OF MEDICINE

Pregnancy increases the sensitivity of the bile
ducts to estrogen, and cholestasis often develops during the second and third trimesters of pregnancy. This
condition is the second most common cause of jaundice during pregnancy, but generalized itching (pruritus gravidarum) is the only symptom most women
experience. Cholestasis of pregnancy tends to run in
families. Symptoms usually disappear within two to
four weeks after the baby’s birth but may reappear if
the woman becomes pregnant again.
A similar condition affects some women who take
birth control pills. Symptoms disappear after the
woman stops using oral contraceptives. This condition
does not lead to chronic liver disease. A woman who
develops cholestasis from either of these causes (pregnancy or birth control hormones) has an increased risk
of developing cholestasis from the other.

resembling chronic biliary cirrhosis (a progressive disease characterized by destruction of small bile ducts)
persists even after the medication is stopped. Some
patients experience a similar reaction in response to
tricyclic antidepressants (amitriptyline, imipramine),
phenylbutazone (Butazolidin), erythromycin estolate
(Estomycin, Purmycin), and other drugs. Intrahepatic
cholestasis may also be caused by alcoholic liver disease, primary biliary cirrhosis, cancer that has spread
(metastasized) from another part of the body, and a
number of rare disorders.
Extrahepatic cholestasis is most often caused by a
stone obstructing the passage through which bile travels from the gallbladder to the small intestine (common bile duct) or by pancreatic cancer. Less often, the
condition occurs as a result of non-cancerous narrowing of the common duct (strictures), ductal carcinoma,
or disorders of the pancreas.
Cholestasis caused by the use of steroids causes
little, if any, inflammation. Symptoms develop gradually and usually disappear after the drug is discontinued. Other drugs that can cause cholestasis include:

Benign familial recurrent cholestasis is a rare condition characterized by brief, repeated episodes of
itching and jaundice. Symptoms often disappear.
This condition does not cause cirrhosis.



allopurinol (Zyloprim)



amitriptyline (Elavil)



azathioprine (Imuran)

Drug-induced cholestasis may be a complication
of chemotherapy or other medications. The two major
types of drug-induced cholestasis are direct toxic
injury and reactions unique to an individual (idiosyncratic reactions). In direct toxic injury, the severity of
symptoms parallels the amount of medication
involved. This condition:



benoxaprofen (Oraflex)



capotril (Capoten)



carbamazepine (Tegretol)



cimetidine (Tagamet)



hydralazine hydrochloride (Apresoline Hydrochloride)



imipramine (Tofranil)



penicillin



quinidine sulfate (Quinidex)



ranitidine (Zantac)



sulfonamides (Apo-Sulfatrim, sulfamethoxazole)



sulindac (Clinoril, Saldac)



develops a short time after treatment begins



follows a predictable pattern



usually causes liver damage

Direct toxic reactions develop in 1% of all
patients who take chlorpromazine (Thorazine), a tranquilizer and antinausea drug. Idiosyncratic reactions
may occur at the onset of treatment or at a later time.
Allergic responses are varied and are not related to the
amount of medication being taken.

Symptoms of both intrahepatic and extrahepatic
cholestasis include a yellow discoloration of the skin
(jaundice), dark urine, and pale stools. Itching over the
skin may be severe if the condition is advanced.

Causes and symptoms
Intrahepatic cholestasis is usually caused by hepatitis or by medications that can produce symptoms
resembling hepatitis. Phenothiazine-derivative drugs,
including chlorpromazine, can cause sudden fever and
inflammation. Symptoms usually disappear after use
of the drug(s) is stopped. In rare cases, a condition
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms of chronic cholestasis include:


skin discoloration



scars or skin injuries caused by scratching



bone pain



yellowish fat deposits beneath the surface of the skin
(xanthoma) or around the eyes (xanthelasma)
865

Cholestasis

of surgery, serious injury, tissue-destroying infection, or
intravenous feeding. Extrahepatic cholestasis can be
caused by conditions such as tumors and gallstones
that block the flow of bile from the gallbladder to the
first part of the small intestine (duodenum).

Cholestasis

Patients with advanced cholestasis feel ill, tire
easily, and are often nauseated. Abdominal pain and
such systemic symptoms as anorexia, vomiting, and
fever are usually due to the underlying condition that
causes cholestasis.

Diagnosis
Determining whether obstruction exists inside
or outside the liver is the essential part of diagnosis.
A history of hepatitis or heavy drinking, recent use of
certain drugs, and symptoms like ascites (abnormal
abdominal swelling) and splenomegaly (enlarged
spleen) suggest intrahepatic cholestasis. Pain or rigidity in the gallbladder or pancreas suggest an extrahepatic form.
Blood tests and liver function tests can reveal the
pattern and extent of liver injury, indicate functional
abnormalities, and establish the cause of the condition. However, most misdiagnoses occur when physicians rely more on laboratory analysis than on
detailed medical history and the results of a thorough
physical examination. Special attention should be paid
to three liver function tests. Levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and
aspartate aminotransferase (AST) can indicate
whether the patient’s condition is caused by an
obstructive condition like cholestasis or a disease of
the liver cells (hepatocellular disease) like viral hepatitis or cancer. ALP levels more than three times greater
than normal indicate cholestasis. High levels of AST
and particularly of ALT, which is found predominantly in liver cells, indicate hepatocellular disease.
Once the disease pattern has been established,
ultrasound may be performed to determine whether
obstruction of the large duct has caused widening of
small ducts located close to it. Computed tomography
scans (CT) and magnetic resonance imaging (MRI) can
provide more detailed information about the source of
the obstruction. If these procedures that do not enter
the patient’s body (non-invasive procedures) do not
provide the information a family physician, internist,
or gastroenterologist needs to make a diagnosis of cholestasis, one of these procedures may be performed:


direct cholangiography, an x-ray map of the bile
ducts, enhanced by the use of contrast dye



percutaneous transhepatic cholangiography, used to
identify obstructions that impede the flow of bile
from the liver to the digestive system, takes x-ray
images of the bile ducts after a contrast dye has
been injected by a needle passed directly into a hepatic duct

866

KEY TERMS
Bile—A bitter yellow-green substance produced
by the liver. Bile breaks down fats in the small
intestine so that they can be used by the body. It
is stored in the gallbladder and passes from the
gallbladder through the common bile duct to the
top of the small intestine (duodenum) as needed to
digest fat.
Biliary—Of bile or of the gallbladder and bile ducts
that transport bile and make up the biliary system or
tract.
Computed tomography scans (CT)—An imaging
technique in which cross-sectional x rays of the
body are compiled to create a three-dimensional
image of the body’s internal structures.
Endoscopic retrograde cholangiopancreatography—
A diagnostic procedure for mapping the pancreatic
and common bile ducts. A flexible tube with a light
transmitter (fiberoptics) is placed in the duct. A
contrast dye is instilled directly into the duct and
a series of x-ray images are taken.
Hepatic—Of the liver, from the Greek hepar.
Liver function tests—Tests used to evaluate liver
metabolism, storage, filtration, and excretion. The
tests include alkaline phosphatase and serum alanine
aminotransferase and aspartate aminotransferase.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Percutaneous transhepatic cholangiography—An
x-ray examination of the bile ducts. A needle is
passed through the skin (percutaneous) across or
over the liver (transhepatic) and directly into a bile
duct to inject a contrast dye. The dye enhances the
x-ray image mapping the system of bile ducts
(cholangiography).
Phenothiazine-derivative drugs—A large family of
drugs derived from phenothiazine, a compound that
in itself is too poisonous for human consumption.
Phenothiazine derivatives include tranquilizers,
medications that prevent vomiting, antihistamines,
and drugs used to enhance the effectiveness of
anesthesia.
Ultrasonography—A test using sound waves to
measure blood flow. Gel is applied to a hand-held
transducer that is pressed against the patient’s
body. Images are displayed on a monitor.

GALE ENCYCLOPEDIA OF MEDICINE

endoscopic retrograde cholangiopancreatography
(ERCP), which uses a special dye to outline the pancreatic and common bile ducts and highlight the
position of any obstruction; a special tube with a
light transmitter is inserted into the duct and a series
of x-ray images is taken

A doctor who thinks a physical obstruction is
responsible for progressive deterioration of a patient’s
condition may consider an exploratory surgical procedure (diagnostic laparotomy). Liver biopsy is sometimes performed if imaging tests do not indicate why a
duct is enlarged, but results of a single biopsy may not
represent the status of the entire organ.

Treatment
The goal of treatment is to eliminate or control the
patient’s symptoms. Discontinuing the use of certain
drugs can restore normal liver function, but surgery
may be needed to drain or remove obstructions or to
widen affected ducts.
Rifampin (Rifadin, Rimactane), an antibacterial
drug; phenobarbital, a barbiturate anticonvulsant;
and other drugs are sometimes prescribed to cleanse
the system and eliminate bile salts and other toxic
compounds.
Patients who have chronic cholestasis and have
trouble digesting fat may have to restrict the amount
of fat in their diet and take calcium and water-soluble
vitamin supplements. A liver transplant may become
necessary if complications occur.

Prognosis
Symptoms almost always disappear after the
underlying condition is controlled.
Some patients who have cholestasis experience
symptoms only after infection develops, but chronic
bile-duct obstruction always leads to cirrhosis. It may
also cause osteoporosis (fragile bones) or osteomalacia
(soft bones).

National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Maureen Haggerty

I Cholesterol, high
Definition
Cholesterol is a fatty substance found in animal
tissue and is an important component to the human
body. It is manufactured in the liver and carried
throughout the body in the bloodstream. Problems
can occur when too much cholesterol forms an accumulation of plaque on blood vessel walls, which
impedes blood flow to the heart and other organs.
The highest cholesterol content is found in meat, poultry, shellfish, and dairy products.

Description
Cholesterol is the Dr. Jekyll and Mr. Hyde of
medicine, since it has both a good side and bad side.
It is necessary to digest fats from food, make hormones, build cell walls, and participate in other processes for maintaining a healthy body. When people
talk about cholesterol as a medical problem, they
usually are referring to high cholesterol. This can be
somewhat misleading, since there are four components to cholesterol. These are:


LDL, the so-called bad cholesterol



HDL, the so-called good cholesterol



triglycerides, a blood fat lipid that increases the risk
for heart disease



total cholesterol

ORGANIZATIONS

High LDL (low-density lipoprotein) is a major
contributing factor of heart disease. The cholesterol
forms plaque in the heart’s blood vessels, which
restricts or blocks the supply of blood to the heart,
and causes a condition called atherosclerosis. This can
lead to a ‘‘heart attack,’’ resulting in damage to the
heart and possibly death. The U.S. Food and Drug
Administration (FDA) estimates that 90 million
American adults, roughly half the adult population,
have elevated cholesterol levels.

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.

The population as a whole is at some risk of
developing high LDL cholesterol in their lifetimes.
Specific risk factors include a family history of high

Emergency care is not required unless inflammation of the bile ducts (cholangitis) develops. Cancer
should be considered when an adult suddenly develops
cholestasis after the age of 50.
Resources

GALE ENCYCLOPEDIA OF MEDICINE

867

Cholesterol, high



Cholesterol, high

Types Of Cholesterol

Types

Levels

Total Cholesterol:
Desirable
Borderline
Undesirable

<200
200 to 240
>240

HDL cholesterol:
Desirable
Borderline
Undesirable
LDL cholesterol:
Desirable
Borderline
Undesirable

>45
35 to 45
<35
<130
130 to 160
>160

Ratio of total cholesterol to HDL cholesterol:
Desirable
<3
Borderline
3 to 4
Undesirable
>4

cholesterol, obesity, heart attack or stroke, alcoholism,
and lack of regular exercise. The chances of developing high cholesterol increase after the age of 45. One of
the primary causes of high LDL cholesterol is too
much fat or sugar in the diet, a problem especially
true in the United States. Cholesterol also is produced
naturally in the liver and overproduction may occur
even in people who limit their intake of high cholesterol food. Low HDL and high triglyceride levels are
also risk factors for atherosclerosis.

Causes and symptoms
There are no readily apparent symptoms that
indicate high LDL or triglycerides, or low HDL. The
only way to diagnose the problems is through a simple
blood test. However, one general indication of high
cholesterol is obesity. Another is a high-fat diet.

Diagnosis
High cholesterol often is diagnosed and treated by
general practitioners or family practice physicians. In
some cases, the condition is treated by an endocrinologist or cardiologist. Total cholesterol, LDL, HDL,
and triglyceride levels as well as the cholesterol to
HDL ratio are measured by a blood test called a
lipid panel. The cost of a lipid panel is generally
$40–100 and is covered by most health insurance and
HMO plans, including Medicare, providing there is an
appropriate reason for the test. Home cholesterol testing kits are available over the counter but test only for
total cholesterol. The results should only be used as a
868

guide and if the total cholesterol level is high or low, a
lipid panel should be performed by a physician. In
most adults the recommended levels, measured by
milligrams per deciliter (mg/dL) of blood, are: total
cholesterol, less than 200; LDL, less than 130; HDL,
more than 35; triglycerides, 30–200; and cholesterol to
HDL ratio, four to one. However, the recommended
cholesterol levels may vary, depending on other risk
factors such as hypertension, a family history of heart
disease, diabetes, age, alcoholism, and smoking.
Doctors have always been puzzled by why some
people develop heart disease while others with identical HDL and LDL levels do not. New studies indicate
it may be due to the size of the cholesterol particles in
the bloodstream. A test called a nuclear magnetic
resonance (NMR) LipoProfile exposes a blood sample
to a magnetic field to determine the size of the cholesterol particles. Particle size also can be determined by a
centrifugation test, where blood samples are spun very
quickly to allow particles to separate and move at
different distances. The smaller the particles, the
greater the chance of developing heart disease. It
allows physicians to treat patients who have normal
or close to normal results from a lipid panel but
abnormal particle size.

Treatment
A wide variety of prescription medicines are available to treat cholesterol problems. These include statins such as Mevacor (lovastatin), Lescol (fluvastatin),
Pravachol (pravastatin), Zocor (simvastatin), Baycol
(cervastatin), and Lipitor (atorvastatin) to lower
LDL. A group of drugs called fibric acid derivatives
are used to lower triglycerides and raise HDL. These
include Lopid (gemfibrozil), Atromid-S (clofibrate),
and Tricor (fenofibrate). Doctors decide which drug
to use based on the severity of the cholesterol problem,
side effects, and cost.

Alternative treatment
The primary goal of cholesterol treatment is to
lower LDL to under 160 mg/dL in people without
heart disease and who are at lower risk of developing
it. The goal in people with higher risk factors for heart
disease is less than 130 mg/dL. In patients who already
have heart disease, the goal is under 100 mg/dL,
according to FDA guidelines. Also, since low HDL
levels increase the risks of heart disease, the goal of all
patients is more than 35 mg/dL.
In both alternative and conventional treatment of
high cholesterol, the first-line treatment options are
GALE ENCYCLOPEDIA OF MEDICINE

Diet and exercise
Since a large number of people with high cholesterol are overweight, a healthy diet and regular exercise are probably the most beneficial natural ways to
control cholesterol levels. In general, the goal is to
substantially reduce or eliminate foods high in animal
fat. These include meat, shellfish, eggs, and dairy products. Several specific diet options are beneficial. One
is the vegetarian diet. Vegetarians typically get up to
100% more fiber and up to 50% less cholesterol from
food than non-vegetarians. The vegetarian low-cholesterol diet consists of at least six servings of whole
grain foods, three or more servings of green leafy
vegetables, two to four servings of fruit, two to four
servings of legumes, and one or two servings of non-fat
dairy products daily.
A second diet is the Asian diet, with brown rice
being the staple. Other allowable foods include fish,
vegetables such as bok choy, bean sprouts, and black
beans. It allows for one weekly serving of meat and
very few dairy products. The food is flavored with
traditional Asian spices and condiments, such as ginger, chilies, turmeric, and soy sauce.
Another regimen is the low glycemic or diabetic
diet, which can raise the HDL (good cholesterol) level
by as much as 20% in three weeks. Low glycemic foods
promote a slow but steady rise in blood sugar levels
following a meal, which increases the level of HDL.
They also lower total cholesterol and triglycerides.
Low glycemic foods include certain fruits, vegetables,
beans, and whole grains. Processed and refined foods
and sugars should be avoided.
Exercise is an extremely important part of lowering
bad cholesterol and raising good cholesterol. It should
consist of 20–30 minutes of vigorous aerobic exercise at
least three times a week. Exercises that cause the heart
to beat faster include fast walking, bicycling, jogging,
roller skating, swimming, and walking up stairs. There
are also a wide selection of aerobic programs available
at gyms or on videocassette.
Garlic
A number of clinical studies have indicated that
garlic can offer modest reductions in cholesterol. A
1997 study by nutrition researchers at Pennsylvania
State University found men who took garlic capsules
GALE ENCYCLOPEDIA OF MEDICINE

for five months reduced their total cholesterol by
7% and LDL by 12%. Another study showed that
seven cloves of fresh garlic a day significantly
reduced LDL, as did a daily dose of four garlic
extract pills. Other studies in 1997 and 1998 back
up these results. However, two more recent studies
have questioned the effectiveness of garlic in lowering ‘‘bad cholesterol.’’
Cholestin
Cholestin hit the over-the-counter market in 1997
as a cholesterol-lowering dietary supplement. It is a
processed form of red yeast fermented with rice, a
traditional herbal remedy used for centuries by the
Chinese. Two studies released in 1998 showed
Cholestin lowered LDL cholesterol by 20–30%. It
also appeared to raise HDL and lower triglyceride
levels. Although the supplement contains hundreds
of compounds, the major active LDL-lowering ingredient is lovastatin, a chemical also found in the prescription drug Mevacor. The FDA banned Cholestin
in early 1998 but a federal district court judge lifted the
ban a year later, ruling the product was a dietary
supplement, not a drug. It is not fully understood
how the substance works and patients may want to
consult with their physician before taking Cholestin.
No serious side effects have been reported, but minor
side effects, including bloating and heartburn, have
been reported.
Other treatments
One study indicated that blue-green algae contains
polyunsaturated fatty acids that lower cholesterol.
The algae, known as alga Aphanizomenon flos-aquae
(AFA) is available as an over-the-counter dietary supplement. Niacin, also known as nicotinic acid or vitamin B3, has been shown to reduce LDL levels by
10–20%, and raise HDL levels by 15–35%. It also can
reduce triglycerides. But because an extremely high dose
of niacin (2–3) is needed to treat cholesterol problems, it
should only be taken under a doctor’s supervision to
monitor possible toxic side effects. Niacin also can cause
flushing when taken in high doses. Soy protein with
high levels of isoflavones also have been shown to
reduce bad cholesterol by up to 10%. A daily diet that
contains 62 mg of isoflavones in soy protein is recommended, and can be incorporated into other diet regimens, including vegetarian, Asian, and low glycemic. In
2003, research revealed that policosanol, a substance
made from sugar cane wax or beeswax, lowered
LDL cholesterol nearly 27% in study subjects in a
Cuban study.
869

Cholesterol, high

exercise, diet, weight loss, and stopping smoking.
Other alternative treatments include high doses of
niacin, soy protein, garlic, algae, and the Chinese
medicine supplement Cholestin (a red yeast fermented
with rice).

Cholesterol-reducing drugs

KEY TERMS
Atherosclerosis—A buildup of fatty substances in
the inner layers of the arteries.
Estrogen—A hormone that stimulates development
of female secondary sex characteristics.
Glycemic—The presence of glucose in the blood.
Hypertension—Abnormally high blood pressure in
the arteries.
Legumes—A family of plants that bear edible seeds
in pods, including beans and peas.
Lipid—Any of a variety of substances that, along
with proteins and carbohydrates, make up the main
structural components of living cells.
Polyunsaturated fats—A non-animal oil or fatty
acid rich in unsaturated chemical bonds not associated with the formation of cholesterol in the
blood.

Prognosis
High cholesterol is one of the key risk factors for
heart disease. Left untreated, too much bad cholesterol can clog the blood vessels, leading to chest pain
(angina), blood clots, and heart attacks. Heart disease
is the number one killer of men and women in the
United States. By reducing LDL, people with heart
disease may prevent further heart attacks and strokes,
prolong and improve the quality of their lives, and
slow or reverse cholesterol build up in the arteries. In
people without heart disease, lowering LDL can
decrease the risk of a first heart attack or stroke.

not meet the criteria for high cholesterol but no definitive results are available.
Resources
BOOKS

Bratman, Steven, and David Kroll. Natural Pharmacist:
Natural Treatments for High Cholesterol. Roseville,
CA: Prima Publishing, 2000.
Ingels, Darin. The Natural Pharmacist: Your Complete Guide
to Garlic and Cholesterol. Roseville, CA: Prima
Publishing, 1999.
Murray, Michael T. Natural Alternatives to Over-theCounter and Prescription Drugs. New York: William
Morrow & Co., 1999.
PERIODICALS

Carter, Ann. ‘‘Cholesterol in Your Diet.’’ Clinical Reference
Systems July 1, 1999: 282.
‘‘Eating a Vegetarian Diet that Includes Cholesterol-lowering Foods may Lower Lipid Levels as Much as Some
Medications.’’Environmental Nutrition March 2003:8.
Marandino, Cristin. ‘‘The Case for Cholesterol.’’ Vegetarian
Times August 1999: 10.
Sage, Katie. ‘‘Cut Cholesterol with Policosanol: This
Supplement Worked Better than a Low-fat Diet in One
Study.’’Natural Health March 2003: 32.
Schmitt, B.D. ‘‘Treating High Cholesterol Levels.’’ Clinical
Reference Systems July 1, 1999: 1551.
VanTyne, Julia, and Lori Davis. ‘‘Drop Your Cholesterol 25
to 100 Points.’’ Prevention November 1999: 110.
ORGANIZATIONS

National Cholesterol Education Program. NHLBI
Information Center, P.O. Box 30105, Bethesda, MD
20824-0105. <http://www.nhlbi.nih.gov>.

Ken R. Wells
Teresa G. Odle

Prevention
The best way to prevent cholesterol problems is
through a combination of healthy lifestyle activities, a
primarily low-fat and high-fiber diet, regular aerobic
exercise, not smoking, and maintaining an optimal
weight. In a small 2003 Canadian study, people who
ate a low-fat vegetarian diet consisting of foods that
are found to help lower cholesterol dropped their
levels of LDL cholesterol as much as results from
some statin drugs. But for people with high risk factors
for heart disease, such as a family history of heart
disease, diabetes, and being over the age of 45, these
measures may not be enough to prevent the onset of
high cholesterol. There are studies being done on the
effectiveness of some existing anti-cholesterol drugs
for controlling cholesterol levels in patients who do
870

I Cholesterol-reducing drugs
Definition
Cholesterol-reducing drugs are medicines that
lower the amount of cholesterol (a fat-like substance)
in the blood.

Purpose
Cholesterol is a chemical that can both benefit and
harm the body. On the good side, cholesterol plays
important roles in the structure of cells and in the
production of hormones. But too much cholesterol in
the blood can lead to heart and blood vessel disease.
GALE ENCYCLOPEDIA OF MEDICINE

Many factors may contribute to the fact that some
people have higher cholesterol levels than others. A
diet high in certain types of fats is one factor. Medical
problems such as poorly controlled diabetes, an
underactive thyroid gland, an overactive pituitary
gland, liver disease or kidney failure also may cause
high cholesterol levels. And some people have inherited
disorders that prevent their bodies from properly
using and eliminating fats. This allows cholesterol to
build up in the blood.
Treatment for high cholesterol levels usually
begins with changes in daily habits. By losing weight,
stopping smoking, exercising more and reducing the
amount of fat and cholesterol in the diet, many people
can bring their cholesterol levels down to acceptable
levels. However, some may need to use cholesterolreducing drugs to reduce their risk of health problems.

Description
There are four different classes of cholesterol lowering drugs:
Bile acid sequesterants are drugs that act by binding with the bile produced by the liver. Bile helps the
digestion and absorption of fats in the intestine. By
blocking the digestion of fats, bile acid sequesterants
prevent the formation of cholesterol. Drugs in this
class include: cholestyramine (Questran); colestipol
(Colestid); and colesevalam (Welchol).
HMG-CoA inhibitors, often called ‘‘statins,’’ are
drugs that block an enzyme called ‘‘3-hydroxy-3methyl-glutaryl-coenzyme A reductase.’’ This blocks
one of the steps in converting fat to cholesterol. These
are the most effective cholesterol lowering agents available and in recent years have received increased attention for their benefits beyond helping patients with high
cholesterol. In 2003, researchers reported that people
with heart failure but no coronary artery disease
received benefits after only 14 weeks of statin therapy.
In addition, some research has connected the drugs to
reduced risk for depression and dementia. Drugs in this
GALE ENCYCLOPEDIA OF MEDICINE

group include: atorvastatin (Lipitor); cerivastatin
(Baycol); fluvastatin (Lescol); lovastatin (Mevacor);
pravastatin (Pravachol); simvastatin (Zocor); and the
newest approved drug rosuvastatin (Crestor).
Fibric acid derivatives include clofibrate
(Atromid-S); gemfibrozil (Lopid); and fenofibrate
(Tricor). Although these drugs are less effective than
the statins at lowering total cholesterol, they may be
able to lower the low-density lipoprotein (LDL) cholesterol while raising the high-density lipoprotein
(HDL) cholesterol. They probably act by inhibiting
lipoprotein lipase activity.
Niacin, or vitamin B-3, also is effective in lowering
cholesterol levels. Although the normal vitamin dose
of niacin is only 20 mg, the dose required to reduce
cholesterol levels is at least 500 mg each day. Niacin
probably helps reduce cholesterol by inhibiting very
low density lipoprotein (VLDL) secretion in the
bloodstream.

Recommended dosage
The recommended dosage depends on the type of
cholesterol-reducing drug used. The prescribing physician or the pharmacist who filled the prescription can
advise about the correct dosage.
Cholesterol-reducing drugs should be taken
exactly as directed and doses should not be missed.
Double doses should not be taken to make up for a
missed dose.
Physicians may prescribe a combination of cholesterol-reducing drugs, such as pravastatin and colestipol. Following the directions for how and when to
take the drugs is very important. The medicine may
not work properly if both drugs are taken at the same
time of day.
Niacin should not be taken at the same time as an
HMG-CoA inhibitor, as this combination may cause
severe muscle problems. If niacin is taken in an overthe-counter form, both the prescribing physician and
pharmacist should be informed. There are no problems
when the niacin is taken in normal doses as a vitamin.
The prescription should not be stopped without
first checking with the physician who prescribed it.
Cholesterol levels may increase when the medicine is
stopped, and the physician may prescribe a special diet
to make this less likely.

Precautions
Seeing a physician regularly while taking cholesterol-reducing drugs is important. The physician will
871

Cholesterol-reducing drugs

To complicate matters, not all cholesterol contributes
to heart and blood vessel problems. One type, called
high-density lipoprotein (HDL) cholesterol, or ‘‘good
cholesterol,’’ actually lowers the risk of these problems.
The other type, low-density lipoprotein (LDL) cholesterol, or ‘‘bad cholesterol,’’ is the type that threatens
people’s health. The names reflect the way cholesterol
moves through the body. To travel through the bloodstream, cholesterol must attach itself to a protein. The
combination of a protein and a fatty substance like
cholesterol is called a lipoprotein.

Cholesterol-reducing drugs

check to make sure the medicine is working as it
should and will decide whether it is still needed.
Blood tests and other medical tests may be ordered
to help the physician monitor the drug’s effectiveness
and check for side effects.
For most people, cholesterol-reducing drugs are
just one part of a whole program for lowering cholesterol levels. Other important elements of the program
may include weight loss, exercise, special diets, and
changes in other habits. The medication should never
be viewed as a substitute for other measures ordered
by the physician. Cholesterol-reducing drugs will not
cure problems that cause high cholesterol; they will
only help control cholesterol levels.
People over 60 years of age may be unusually
sensitive to the effects of some cholesterol-reducing
drugs. This may increase the chance of side effects.
Anyone who is taking an HMG-CoA reductase
inhibitor should notify the health care professional in
charge before having any surgical or dental procedures or receiving emergency treatment.
Special conditions
People who have certain medical conditions or
who are taking certain other medications may have
problems if they take cholesterol-reducing drugs.
Before taking these drugs, the prescribing physician
should be informed of any of the following conditions:
ALLERGIES. Anyone who has had unusual reactions to cholesterol-reducing drugs in the past should
inform the prescribing physician before taking the
drugs again. The physician also should be told about
any allergies to foods, dyes, preservatives, or other
substances.
PREGNANCY. Studies of laboratory animals have

shown that giving high doses of gemfibrozil during
pregnancy increases the risk of birth defects and other
problems, including death of the unborn baby. The
effects of this drug have not been studied in pregnant
women. Women who are pregnant or who may
become pregnant should check with their physicians
before using gemfibrozil.
Cholesterol-reducing drugs in the group known
as HMG-CoA reductase inhibitors (such as lovastatin, fluvastatin, pravastatin and simvastatin)
should not be taken by women who are pregnant or
who plan to become pregnant soon. By blocking the
production of cholesterol, these drugs prevent a fetus
from developing properly. Women who are able to
bear children should use an effective birth control
method while taking these drugs. Any woman who
872

becomes pregnant while taking these drugs should
check with her physician immediately.
Cholestyramine and colestipol will not directly
harm an unborn baby, because these drugs are not
taken into the body. However, the drugs may keep
the mother’s body from absorbing vitamins that she
and the baby need. Pregnant women who take these
drugs should ask their physicians whether they need to
take extra vitamins.
BREASTFEEDING. Because cholestyramine and
colestipol interfere with the absorption of vitamins,
women who use these drugs while breastfeeding
should ask their physicians if they need to take extra
vitamins.

Women who are breastfeeding should talk to their
physicians before using gemfibrozil. Whether this
drug passes into breast milk is not known. But
because animal studies suggest that it may increase
the risk of some types of cancer, women should carefully consider the safety of using it while breastfeeding.
HMG-CoA reductase inhibitors (such as lovastatin, pravastatin, fluvastatin and simvastatin)
should not be used by women who are breastfeeding
their babies.
OTHER
MEDICAL
CONDITIONS. Cholesterolreducing drugs may make some medical problems
worse. Before using these drugs, people with any of
these medical conditions should make sure their physicians are aware of their conditions:


stomach problems, including stomach ulcer



constipation



hemorrhoids



gallstones or gallbladder disease



bleeding problems



underactive thyroid



heart or blood vessel disease

In addition, people with kidney or liver disease
may be more likely to have blood problems or other
side effects when they take certain cholesterolreducing drugs. And some drugs of this type may actually raise cholesterol levels in people with liver disease.
Patients with any of the following medical conditions may develop problems that could lead to kidney
failure if they take HMG-CoA reductase inhibitors:


treatments to prevent rejection after an organ
transplant



recent major surgery



seizures (convulsions) that are not well controlled
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cell—The basic unit that makes up all living tissue.
Cholesterol—Fatty substance found in tissue.
Necessary to maintain a healthy body.

USE OF CERTAIN MEDICINES. Cholesterol-reducing

drugs may change the effects of other medicines.
Patients should not take any other medicine that has
not been prescribed or approved by a physician who
knows they are taking cholesterol-reducing drugs.

Enzyme—A type of protein, produced in the body,
that brings about or speeds up chemical reactions.
Hormone—A substance that is produced in one part
of the body, then travels through the bloodstream to
another part of the body where it has its effect.

Side effects

Phenylketonuria—(PKU) A genetic disorder in
which the body lacks an important enzyme. If
untreated, the disorder can lead to brain damage
and mental retardation.

Gemfibrozil
Studies in animals and humans suggest that gemfibrozil increases the risk of some types of cancer. The
drug may also cause gallstones or muscle problems.
Patients who need to take this medicine should ask
their physicians for the latest information on its benefits and risks.
Patients taking gemfibrozil should check with a
physician immediately if any of these side effects
occur:


fever or chills



severe stomach pain with nausea and vomiting



pain in the lower back or side



pain or difficulty when urinating



cough or hoarseness
HMG-CoA reductase inhibitors

These drugs may damage the liver or muscles.
Patients who take the drugs should have blood tests
to check for liver damage as often as their physician
recommends. Any unexplained pain, tenderness or
weakness in the muscles should be reported to the
physician at once.
All cholesterol-reducing drugs
Minor side effects such as heartburn, indigestion,
belching, bloating, gas, nausea or vomiting, stomach
pain, dizziness and headache usually go away as the
body adjusts to the drug and do not require medical
treatment unless they continue or they interfere with
normal activities.

Pituitary gland—A pea-sized gland at the base of
the brain that produces many hormones that affect
growth and body functions.

reducing drugs should get in touch with his or her
physician.

Interactions
Cholesterol-reducing drugs may interact with
other medicines. When this happens, the effects of one
or both of the drugs may change or the risk of side
effects may be greater. Anyone who takes cholesterolreducing drugs should let the physician know all other
medicines he or she is taking and should ask whether
the possible interactions can interfere with drug therapy. Examples of possible interactions are listed below.
Some cholesterol-reducing drugs may prevent the
following medicines from working properly:


thyroid hormones



water pills (diuretics)



certain antibiotics taken by mouth, such as tetracyclines, penicillin G and vancomycin



the beta-blocker Inderal, used to treat high blood
pressure



digitalis heart medicines



phenylbutazone, a nonsteroidal anti-inflammatory
drug

Patients who have constipation while taking
cholesterol-reducing drugs should bring the problem
to a physician’s attention as soon as possible.

Taking some cholesterol-reducing drugs with
blood thinners (anticoagulants) may increase the
chance of bleeding.

Additional side effects are possible. Anyone
who has unusual symptoms while taking cholesterol-

Combining HMG-CoA reductase inhibitors with
gemfibrozil, cyclosporine (Sandimmune) or niacin

GALE ENCYCLOPEDIA OF MEDICINE

873

Cholesterol-reducing drugs

People with phenylketonuria (PKU) should be
aware that sugar-free formulations of some cholesterolreducing drugs contain phenylalanine in aspartame.
This ingredient can cause problems in people who have
phenylketonuria.

Cholesterol test

may cause or worsen problems with the kidneys or
muscles.

They contain about 7% cholesterol. Chylomicrons
transport fats and cholesterol from the intestine into
the liver, then into the bloodstream. They are metabolized in the process of carrying food energy to
muscle and fat cells.

Resources
BOOKS

Nesto, R. W., and L. Christensen. Cholesterol-Lowering
Drugs: Everything You and Your Family Need to Know.
New York: Morrow, William & Co, 2000.



Very low-density lipoproteins (VLDL). These lipoproteins carry mostly triglycerides, but they also contain 16–22% cholesterol. VLDLs are made in the
liver and eventually become IDL particles after they
have lost their triglyceride content.



Intermediate-density lipoproteins (IDL). IDLs are
short-lived lipoproteins containing about 30% cholesterol that are converted in the liver to low-density
lipoproteins (LDLs).



Low-density lipoproteins (LDL). LDL molecules
carry cholesterol from the liver to other body tissues.
They contain about 50% cholesterol. Extra LDLs
are absorbed by the liver and their cholesterol is
excreted into the bile. LDL particles are involved in
the formation of plaques (abnormal deposits of cholesterol) in the walls of the coronary arteries. LDL is
known as ‘‘bad cholesterol.’’



High-density lipoproteins (HDL). HDL molecules
are made in the intestines and the liver. HDLs are
about 50% protein and 19% cholesterol. They help
to remove cholesterol from artery walls. Lifestyle
changes, including exercising, keeping weight within
recommended limits, and giving up smoking can
increase the body’s levels of HDL cholesterol. HDL
is known as ‘‘good cholesterol.’’



Lipoprotein subclasses. By identifying levels of multiple subclasses of lipid abnormalities, physicians can
do a better job of prescribing lipid-lowering therapies, particularly in high-risk patients such as those
with type 2 diabetes.

PERIODICALS

‘‘Cholesterol Drug Helps Heart Failure Patients Without
High Cholesterol.’’ Heart Disease Weekly August 24,
2003: 33.
‘‘Link to Cholesterol Drugs Disputed.’’ Cardiovascular
Week September 29, 2003: 73.
Mechcatie, Elizabeth. ‘‘FDA Okays Rosuvastatin for
Hypercholeterolemia: Most Potent Statin to Date.’’
Internal Medicine News September 1, 2003: 30–31.

Nancy Ross-Flanigan
Teresa G. Odle

I Cholesterol test
Definition
The cholesterol test is a quantitative analysis of
the cholesterol levels in a sample of the patient’s blood.
Total serum cholesterol (TC) is the measurement routinely taken. Doctors sometimes order a complete
lipoprotein profile to better evaluate the risk for atherosclerosis (coronary artery disease, or CAD). The full
lipoprotein profile also includes measurements of triglyceride levels (a chemical compound that forms 95%
of the fats and oils stored in animal or vegetable cells)
and lipoproteins (high density and low density). Blood
fats also are called ‘‘lipids.’’ It is estimated that more
than 200 million cholesterol tests are performed each
year in the United States.
The type of cholesterol in the blood is as important as the total quantity. Cholesterol is a fatty substance and cannot be dissolved in water. It must
combine with a protein molecule called a lipoprotein
in order to be transported in the blood. There are five
major types of lipoproteins in the human body; they
differ in the amount of cholesterol that they carry in
comparison to other fats and fatty acids, and in their
functions in the body. Lipoproteins are classified, as
follows, according to their density:


Chylomicrons. These are normally found in the blood
only after a person has eaten foods containing fats.

874

Because of the difference in density and cholesterol content of lipoproteins, two patients with the
same total cholesterol level can have very different
lipid profiles and different risk for CAD. The critical
factor is the level of HDL cholesterol in the blood
serum. Some doctors use the ratio of the total cholesterol level to HDL cholesterol when assessing the
patient’s degree of risk. A low TC/HDL ratio is associated with a lower degree of risk.

Purpose
The purpose of the TC test is to measure the levels
of cholesterol in the patient’s blood. The patient’s
cholesterol also can be fractionated (separated into
different portions) in order to determine the TC/
HDL ratio. The results help the doctor assess the
GALE ENCYCLOPEDIA OF MEDICINE

In addition, the results of the cholesterol test can
assist the doctor in evaluating the patient’s metabolism of fat, or in diagnosing inflammation of the pancreas, liver disease, or disorders of the thyroid gland.
The frequency of cholesterol testing depends on the
patient’s degree of risk for CAD. People with low cholesterol levels may need to be tested once every five
years. People with high levels of blood cholesterol
should be tested more frequently, according to their
doctor’s advice. The doctor may recommend a detailed
evaluation of the different types of lipids in the patient’s
blood. It is ideal to check the HDL and triglycerides as
well as the cholesterol and LDL. In addition, the
National Cholesterol Education Program (NCEP) suggests further evaluation if the patient has any of the
symptoms of CAD or if she or he has two or more of the
following risk factors for CAD:


male sex



high blood pressure



smoking



diabetes



low HDL levels



family history of CAD before age 55

The necessity of widespread cholesterol screening
is a topic with varying responses. In 2003, a report
demonstrated that measuring the cholesterol of everyone at age 50 years was a simple and efficient way to
identify those most at risk for heart disease from
among the general population.

Precautions
Patients who are seriously ill or hospitalized for
surgery should not be given cholesterol tests because
the results will not indicate the patient’s normal cholesterol level. Acute illness, high fever, starvation, or
recent surgery lowers blood cholesterol levels.

get an accurate triglyceride and LDL level. The blood
is withdrawn by the usual vacuum tube technique
from one of the patient’s veins. The blood test takes
between three and five minutes.

Preparation
Patients who are scheduled for a lipid profile test
should fast (except for water) for 12–14 hours before
the blood sample is drawn. If the patient’s cholesterol
is to be fractionated, he or she also should avoid
alcohol for 24 hours before the test.
Patients also should stop taking any medications
that may affect the accuracy of the test results. These
include corticosteroids, estrogen or androgens, oral
contraceptives, some diuretics, haloperidol, some antibiotics, and niacin. Antilipemics are drugs that lower
the concentration of fatty substances in the blood.
When these are taken by the patient, blood testing
may be done frequently to evaluate the liver function
as well as lipids. The patient’s doctor will give the
patient a list of specific medications to be discontinued
before the test.

Aftercare
Aftercare includes routine care of the skin around
the needle puncture. Most patients have no aftereffects, but some may have a small bruise or swelling.
A washcloth soaked in warm water usually relieves
discomfort. In addition, the patient should resume
taking any prescription medications that were discontinued before the test.

Risks
The primary risk to the patient is a mild stinging
or burning sensation during the venipuncture, with
minor swelling or bruising afterward.

Normal results

A pharmaceutical corporation announced in the
spring of 2004 that it had received an application to
patent a device that could use saliva to determine cholesterol levels. If the test becomes available, it could
make screening much more convenient and accessible.

The ‘‘normal’’ values for serum lipids depend on
the patient’s age, sex, and race. Normal values for
people in Western countries were once presumed to
be 140–220 mg/dL in adults, although as many as 5%
of the population has TC higher than 300 mg/dL.
Among Asians, the figures are about 20% lower. As
a rule, both TC and LDL levels rise as people get older.
However, in 2001, the NCEP released stricter guidelines for LDL and total cholesterol.

The cholesterol test requires a sample of the
patient’s blood. Fasting before the test is required to

Some doctors prefer to speak of ‘‘desired’’ rather
than ‘‘normal’’ cholesterol values, on the grounds that

Description

GALE ENCYCLOPEDIA OF MEDICINE

875

Cholesterol test

patient’s risk for coronary artery disease (CAD). High
LDL levels are associated with increased risk of CAD
whereas high HDL levels are associated with relatively
lower risk.

Cholesterol test

‘‘normal’’ refers to statistically average levels that may
still be too high for good health. The NCEP has outlined the levels according to desirable and risk:


Optimal LDL cholesterol: less than 100 mg/dL and
total cholesterol less than 160 mg/dL



Desirable LDL cholesterol: 100–129 mg/dL; total
cholesterol 160–199 mg/dL



Borderline high risk: LDL cholesterol 130–159 mg/dL;
total cholesterol 200–239 mg/dL



High risk: LDL cholesterol greater than 160 mg/dL;
total cholesterol greater than or at 240 mg/dL.

Abnormal results
It is possible for blood cholesterol levels to be too
low as well as too high.
Abnormally low levels
TC levels less than 160 mg/dL are associated with
higher mortality rates from cancer, liver disease,
respiratory disorders, and injuries. The connection
between unusually low cholesterol and increased mortality is not clear, although some researchers think
that the low level is a secondary sign of the underlying
disease and not the cause of disease or death.
Low levels of serum cholesterol are also associated with malnutrition or hyperthyroidism. Further
diagnostic testing may be necessary in order to locate
the cause.
Abnormally high levels
Prior to 1980, hypercholesterolemia (an abnormally high TC level) was defined as any value above
the 95th percentile for the population. These figures
ranged from 210 mg/dL in persons younger than 20 to
more than 280 mg/dL in persons older than 60. It is
now known, however, that TC levels over 200 mg/dL
are associated with significantly higher risk of CAD.
Levels of 280 mg/dL or more are considered elevated.
Treatment with diet and medication has proven to
successfully lower risk of heart attack and stroke.
Elevated cholesterol levels also may result from
hepatitis, blockage of the bile ducts, disorders of lipid
metabolism, nephrotic syndrome, inflammation of the
pancreas, or hypothyroidism.
Resources
PERIODICALS

Capriotti, Teri. ‘‘Stricter Cholesterol Guidelines Broaden
Implications for the ‘Statin’ Drugs.’’ MedSurg Nursing
February 2003: 51–57.
876

KEY TERMS
Atherosclerosis—A disease of the coronary arteries
in which cholesterol is deposited in plaques on the
arterial walls. The plaque narrows or blocks blood
flow to the heart. Atherosclerosis sometimes is
called coronary artery disease, or CAD.
Fractionation—A laboratory test or process in
which blood or another fluid is broken down into
its components. Fractionation can be used to assess
the proportions of the different types of cholesterol
in a blood sample.
High-density lipoprotein (HDL)—A type of lipoprotein that protects against coronary artery disease by removing cholesterol deposits from
arteries or preventing their formation.
Hypercholesterolemia—The presence of excessively high levels of cholesterol in the blood.
Lipid—Any organic compound that is greasy, insoluble in water, but soluble in alcohol. Fats, waxes,
and oils are examples of lipids.
Lipoprotein—A complex molecule that consists of
a protein membrane surrounding a core of lipids.
Lipoproteins carry cholesterol and other lipids
from the digestive tract to the liver and other
body tissues. There are five major types of
lipoproteins.
Low-density lipoprotein (LDL)—A type of lipoprotein that consists of about 50% cholesterol and is
associated with an increased risk of coronary artery
disease.
Plaque—An abnormal deposit of hardened cholesterol on the wall of an artery.
Triglyceride—A chemical compound that forms
about 95% of the fats and oils stored in animal
and vegetable cells. Triglyceride levels sometimes
are measured as well as cholesterol when a patient
is screened for heart disease.

‘‘Cholesterol Test at Age 50 Spots Those in Greatest
Danger.’’ Heart Disease Weekly July 27, 2003: 3.
‘‘Company Wins U.S. Patent for Saliva Cholesterol Test.’’
Heart Disease Weekly May 23, 2004: 66.
‘‘Study Shows Expanded Cholesterol Test Sparked Use
of Lipid-lowering Therapy.’’ Heart Disease Weekly
July 13, 2003: 20.

Rebecca J. Frey, PhD
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Definition

Cholinergic—Nerves that are stimulated by
acetylcholine.
Glaucoma—A disease of the eye marked by
increased pressure within the eyeball that can result
in damage to the optic disk and gradual loss of vision.

Cholinergic drugs are medications that produce the
same effects as the parasympathetic nervous system.

Purpose

Myasthenia gravis—A disease characterized by
progressive weakness and exhaustibility of voluntary muscles without atrophy or sensory disturbance
and caused by an autoimmune attack on acetylcholine receptors at neuromuscular junctions.

Cholinergic drugs produce the same effects as
acetylcholine. Acetylcholine is the most common neurohormone of the parasympathetic nervous system, the
part of the peripheral nervous system responsible for the
every day work of the body. While the sympathetic
nervous system acts during times of excitation, the parasympathetic system deals with everyday activities such
as salivation, digestion, and muscle relaxation.
The cholinergic drugs may be used in several
ways. The cholinergic muscle stimulants are used to
diagnose and treat myasthenia gravis, a disease that
causes severe muscle weakness. This class of drugs
includes ambenonium chloride (Mytelase), edrophonium chloride (Tensilon), neostigmine (Prostigmine),
and piridogstimina (Mestinœn). These drugs are also
widely used in surgery, both to reduce the risk of
urinary retention, and to reverse the effects of the
muscle relaxant drugs that are used in surgery.
Cholinergic drugs are also used in control of glaucoma, a disease that is caused by increased pressure
inside the eye. The most common drugs used for this
purpose are demecarium (Humorsol) and echthiophate (Phospholine iodide).

Description
Cholinergic drugs usually act in one of two
ways. Some directly mimic the effect of acetylcholine,
while others block the effects of acetylcholinesterase.
Acetylcholinesterase is an enzyme that destroys naturally occurring acetylcholine. By blocking the enzyme,
the naturally occurring acetylcholine has a longer
action.

Recommended dosage
Cholinergic drugs are available only by prescription. They may be available as eye drops, capsules,
tablets, or injections.

Precautions
Cholinergic drugs should be avoided when the
patient has any sort of obstruction in the urinary or
GALE ENCYCLOPEDIA OF MEDICINE

Parasympathetic nervous system—The part of the
nervous system that contains chiefly cholinergic
fibers, that tends to induce secretion, to increase
the tone and contractility of smooth muscle, and to
slow the heart rate.

digestive tracts, such a a tumor, or severe inflammation which is causing blockage.
They should be used with caution in patients with
asthma, epilepsy, slow heart beat, hyperthyroidism, or
gastric ulcers.
The effects of the cholinergic drugs are to produce the same effects as stimulation of the parasympathetic nervous system. These effects include
slowing of the heartbeat, increases in normal secretions including the digestive acids of the stomach,
saliva and tears. For this reason, patients who
already have a problem in one of these areas, such
as a slow heartbeat or stomach ulcers, should use
these drugs with great caution, since the medication
will make their conditions worse.

Side effects
When used properly, cholinergic drugs will
increase muscle strength in patients with myasthenia
gravis. In eye drop form, they can reduce the intraoccular pressure in glaucoma.
The possible adverse effects of cholinergic drugs are:


slow heart beat, possibly leading to cardiac arrest.



muscle weakness, muscle cramps, and muscle pain



convulsions



weak breathing, inability to breath



increased stomach acid and saliva
877

Cholinergic drugs

I Cholinergic drugs

Chondromalacia patellae



nausea and vomiting



izziness, drowsiness, and headache

of the knee, or it may be intermittent and brought on
by squatting, kneeling, going up or down stairs, especially down, or by repeated bending of the joint.

Resources

Diagnosis

PERIODICALS

‘‘Classic Papers in Glaucoma.’’ Archives of Ophthalmology
March 2001.
‘‘Congenital myasthenic syndromes: recent advances.’’
Archives of Neurology February 1999.

Samuel D. Uretsky, PharmD

I Chondromalacia patellae
Definition
Chondromalacia patellae refers to the progressive
erosion of the articular cartilage of the knee joint, that
is the cartilage underlying the kneecap (patella) that
articulates with the knee joint.

Description
Chondromalacia patellae (CMP), also known as
patello-femoral pain syndrome or patello-femoral
stress syndrome, is a syndrome that causes pain/discomfort at the front of the knee. It is associated with
irritation or wear on the underside of the kneecap, or
patella. In a normal knee, the articular cartilage is
smooth and elastic and glides smoothly over the surface of the thighbone, or femur, when the knee is bent.
Erosion of the cartilage roughens the surface and prevents this smooth action.
CMP is most common in adolescent females,
although older people may also develop it. An average
of two out of 10,000 people develop this condition,
many of them runners or other athletes.

Causes and symptoms
CMP is the result of the normal aging process,
overuse, injury, or uneven pressures exerted on the
knee joint. In teens, CMP may be caused by uneven
growth or uneven strength in the thigh muscles.
Growth spurts, common in teens, may result in a
mildly abnormal alignment of the patella, which
increases the angle formed by the thigh and the
patellar tendon (Q-angle). This condition adds to
the damage. Symptoms include pain, normally around
the kneecap, and a grinding sensation felt when
extending the leg. The pain may radiate to the back
878

Diagnosis is established during a physical examination performed by a general practitioner or an
orthopedist, and is based on frequency of symptoms
and confirmed by x rays of the knee. The CMP erosion
can also be seen on an MRI, although this type of scan
is not routinely performed for this purpose. The
patient should inform the doctor about any previous
injuries to the joint.

Treatment
Initial treatment may consist of resting the knee
using crutches, along with aspirin, Tylenol, or a nonsteroidal anti-inflammatory drug (NSAID) such as
Motrin for seven to 10 days. The person should limit
sports activity until the joint is healed and may use ice
followed by heat to decrease inflammation. When the
doctor allows the patient to resume sports, a knee
brace may be prescribed in the form of a stabilizer
with a hole at the kneecap.
Treatment also includes low impact exercises to
strengthen the quadriceps muscles which help stabilize
the knee joint. Physical therapy may be suggested
at the start of this program so as to help the patient
learn the correct method of performing the exercises.
Approximately 85% of people do well with conservative CMP treatment. The remainder still have
severe pain and may require arthroscopic surgery to
repair the tissues inside the knee joint. In more severe
cases, open surgery may be required to realign the
kneecap and perhaps other corrections.

Alternative treatments
Physical therapy offers treatments that may help
CMP patients. Aqua therapy has the benefit of exercising the knee without putting stress on it and it also
strengthens the thigh muscles. Biofeedback can be used
to learn tensing and relaxing specific muscles to relieve
pain. These techniques have the benefit of no side
effects. Massage therapy might be beneficial as well.
Calcium, minerals, and vitamins as part of a balanced
diet will aid healing and help prevent further problems.

Prognosis
In most teens with CMP, the prognosis is excellent
since the damage is reversible when treatment starts
GALE ENCYCLOPEDIA OF MEDICINE

Arthroscopic knee surgery—Surgery performed to
examine or repair tissues inside the knee joint
through a special scope (arthroscope).
Femur—The thigh bone.
Isometric exercises—Exercises which strengthen
through muscle resistance.
Osteoarthritis—Degenerative joint disease.
Quadriceps, hip flexors, hamstrings—Major muscles in the thigh area which affect knee mechanics.

before the cartilage begins to break down. With
proper treatment and preventive techniques, teenagers
will complete their growth without permanent damage
to the joint. Only about 15% of patients require surgical intervention. Older people may go on to develop
osteoarthritis in the knee.

Prevention
Proper exercises are the best preventive measure.
Since tightness of thigh muscles is a risk factor, warming up before athletic activities is recommended, as well
as participating in a variety of sports rather than just
one. Stretching exercises increase flexibility of the quadriceps, hip flexors, and hamstrings. Strengthening exercises such as short arc leg extensions, straight leg raises,
quadriceps isometric exercises, and stationary bicycling
are also recommended.
Resources
OTHER

Chondromalacia patellae. <http://my.webmd.com/content/
asset/adam_disease_chondromalacia_patellae>.
Chondromalacia Patellae. <http://www.orthoseek.com/
articles/chondromp.html>.
‘‘Major Domains of Complementary & Alternative
Medicine.’’ <http://nccam.nih.gov/fcp/classify/>.
Questions and Answers About Knee Problems. <http://
www.cbshealthwatch.com/cx/viewarticle/202777>.
Questions and Answers About Knee Problems. <http://
www.nih.gov/niams/healthinfo/kneeprobs/
kneeqa.htm>.

Barbara J. Mitchell

Chorea see Movement disorders
GALE ENCYCLOPEDIA OF MEDICINE

I Choriocarcinoma
Definition
A choriocarcinoma is type of cancer germ cell
containing trophoblast cells.

Description
Choriocarcinomas are cancers that develop from
germ cells, cells that ordinarily turn into sperm or eggs.
Choriocarcinomas resemble the cells that surround an
embryo in the uterus. Most of these cancers form
inside the reproductive organs. Some originate in the
testes or ovaries, especially in young adults. Others
develop in the uterus after a pregnancy or miscarriage—particularly often after a mole. A few choriocarcinomas arise in sites outside the reproductive
organs. Such ‘‘extragonadal’’ tumors are usually
found in young adults and are more common in males.
Choriocarcinomas are one of the most dangerous
germ cell cancers. Choriocarcinomas usually grow
quickly and spread widely. Occasionally, this cancer
grows so fast that the original tumor outgrows its
blood supply and dies, leaving behind only a small scar.

Causes and symptoms
Choriocarcinomas result from genetic damage to
a germ cell. Males with Klinefelter syndrome are especially likely to develop extragonadal germ cell tumors.
The symptoms of a choriocarcinoma vary,
depending on where the tumor originates and where
it spreads. In the uterus, the most common symptom is
bleeding. Cancers in the ovary often have only subtle
signs such as widening of the waistline or pain. In the
testes, choriocarcinomas can often be felt as small
painless lumps. Choriocarcinomas that spread to
other organs may reveal their presence by bleeding.
In the brain, this bleeding can cause a stroke.

Diagnosis
Choriocarcinomas are usually referred to an
oncologist, a doctor who specializes in cancer treatment. To diagnose this tumor, the doctor will do a
physical examination and examine the internal organs
with x rays or ultrasound studies. Choriocarcinomas
are not always biopsied before being treated, because
they tend to bleed heavily. Spreading of the cancer is
detected with x rays, ultrasound studies, computed
tomography (CT), or magnetic resonance imaging
(MRI) scans.
879

Choriocarcinoma

KEY TERMS

Choriocarcinoma

Most choriocarcinomas make human chorionic
gonadotropin (hCG), a hormone normally found
only during pregnancy. The presence of hCG in the
blood can help diagnose this cancer and monitor the
success of treatment.

Treatment
Choriocarcinomas are usually treated by surgical
removal of the tumor and chemotherapy. Radiation is
occasionally used, particularly for tumors in the brain.

Alternative treatment
Complementary treatments can decrease stress,
reduce the side effects of cancer treatment, and help
patients feel more in control. For instance, some people
find activities such as yoga, massage, music therapy,
meditation, prayer, or mild physical exercise helpful.

Prognosis
The prognosis for choriocarcinomas in the uterus
is very good. Although these tumors have often spread
throughout the body, chemotherapy results in a cure
or remission in at least 80–90% of cases. Women who
have had choriocarcinomas often go on to have normal pregnancies and deliveries.
Choriocarcinomas in other sites have a poorer
prognosis. These tumors tend to spread quickly and
don’t always respond well to chemotherapy. Although
treatment can be effective, the outcome usually depends
on how widely the cancer is dispersed. Generally, the
prognosis is worse if the cancer can be found in the liver
or brain, if hCG levels are high, or if the original tumor
developed outside the gonads. Five-year survival with
testicular cancers can range from 92% for tumors that
have spread only to the lungs to 48% to tumors that
have spread to other internal organs.

Prevention
There is no known means of prevention.
However, early detection of the symptoms and prompt
medical treatment can improve the odds of survival.

KEY TERMS
Biopsy—A sample of an organ taken to look for
abnormalities. Also, the technique used to take
such samples.
Chemotherapy—The treatment of cancer with drugs.
Computed tomography (CT)—A special x ray technique that produces a cross sectional image of the
organs inside the body.
Extragonadal—In a location other than the reproductive organs.
Germ cell—One of the cells that ordinarily develop
into eggs or sperm (also sperm and eggs).
Gonads—The ovaries or testes.
Klinefelter syndrome—A condition caused by
extra X chromosome(s) in a male, that results in
small testes and infertility together with increased
height, decreased facial hair, and sometimes breast
enlargement.
Magnetic resonance imaging—A type of study that
uses changes induced by magnets to see cells and
tissues inside the body.
Mole—A mass of abnormal, partially developed tissues inside the uterus (womb). Moles develop during a
pregnancy that begins with an abnormal fertilization.
Ovaries—The female sex organs that make eggs
and female hormones.
Remission—The disappearance of the symptoms of
cancer, although all of the cancer cells may not be
gone.
Reproductive organs—The group of organs (including the testes, ovaries, and uterus) whose purpose is to
produce a new individual and continue the species.
Testes—The male sex organs that make sperm and
male hormones.
Testicular cancer—A cancer that originates in the
testes.
Trophoblast—The tissues that surround an embryo
and attach it to the uterus.
Tumor—A lump made up of abnormal cells.
Uterus—The organ where a child develops (womb).

Resources
BOOKS

Baker, Vicki V. ‘‘Gestational Trophoblastic Disease.’’ In
Clinical Oncology, edited by Martin D. Abeloff, et al.,
2nd ed. Philadelphia: Churchhill Livingstone, 2000.
Cotran, Ramzi S., Vinay Kumar, and Tucker Collins, editors. ‘‘The Male Genital Tract.’’ In Robbins Pathologic

880

Basis of Disease. 6th ed. Philadelphia: W.B. Saunders,
1999.
Crum, Christopher P. ‘‘The Female Genital Tract.’’ In
Robbins Pathologic Basis of Disease, edited by Ramzi S.
Cotran, Vinay Kumar, and Tucker Collins, 6th ed.
Philadelphia: W.B. Saunders, 1999.
GALE ENCYCLOPEDIA OF MEDICINE

Down syndrome is one in 378 for a 35-year-old
woman and increases to one in 30 for a 45-year-old
woman.


A history of miscarriages or children born with birth
defects.



A family history of genetic disease. Prenatal genetic
testing is recommended if either the mother or father
of the unborn baby has a family history of genetic
disease or is known to be a carrier of a genetic disease.

PERIODICALS

Newlands, Edward S., Fernando J. Paradinas, and
Rosemary A. Fisher. ‘‘Current Therapeutic Issues in
Gynecologic Cancer. Recent Advances in Gestational
Trophoblastic Disease.’’ Hematology/Oncology Clinics
of North America 13, no. 1 (February 1999): 225-44.
OTHER

‘‘Chemotherapy and You: A Guide to Self-help During
Cancer Treatment.’’ CancerNet. June 1999. [cited
April 5, 2001]. <http://cancernet.nci.nih.gov/peb/
chemo_you/index.htm>.
‘‘Extragonadal Germ Cell Tumors.’’ CancerNet. <http://
cancernet.nci.nih.gov/pdq.html>.
‘‘Ovarian Germ Cell Tumor.’’ CancerNet. Feb. 2001. [cited
April 27, 2001]. <http://cancernet.nci.nih.gov/
pdq.html>.

Anna Rovid Spickler, D.V.M., Ph.D.

Chorionic gonadotropin test see Human
chorionic gonadotropin pregnancy test

I Chorionic villus sampling
Definition
Chorionic villus sampling (CVS), also known as
chorionic villus biopsy, is a prenatal test that can
detect genetic and chromosomal abnormalities of an
unborn baby.

Purpose
Chorionic villus sampling is performed on pregnant women who are at risk for carrying a fetus with a
genetic or chromosomal defect. Although it carries a
slightly higher risk, CVS may be used in place of
amniocentesis for women who have one or more of
the following risk factors:


Women age 35 and older. The chance of having a
child with Down syndrome increases with maternal
age. For instance, the chance of having a baby with

GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Chorionic villus sampling is not recommended for
women who have vaginal bleeding or spotting during
the pregnancy. It is not typically recommended for
women who have Rh sensitization from a previous
pregnancy.

Description
Chorionic villus sampling has been in use since the
1980s. This prenatal testing procedure involves taking
a sample of the chorion frondosum–that part of the
chorionic membrane containing the villi–for laboratory analysis. The chorionic membrane is the outer sac
which surrounds the developing fetus. Chorionic villi
are microscopic, finger-like projections that emerge
from the chorionic membrane and eventually form
the placenta. The cells that make up the chorionic
villi are of fetal origin so laboratory analysis can identify any genetic, chromosomal, or biochemical diseases of the fetus.
Chorionic villus sampling is best performed
between 10 and 12 weeks of pregnancy. The procedure
is performed either through the vagina and the cervix
(transcervically) or through the abdomen (transabdominally) depending upon the preferences of the
patient or the doctor. In some cases, the location of the
placenta dictates which method the doctor uses. Both
methods are equally safe and effective. Following the
preparation time, both procedures take only about
five minutes. Women undergoing chorionic villus
sampling may experience no pain at all or feel cramping or pinching. Occasionally, a second sampling procedure must be performed if insufficient villus material
was obtained.
For the transcervical procedure, the woman lies
on an examining table on her back with her feet in
stirrups. The woman’s vaginal area is thoroughly
cleansed with an antiseptic, a sterile speculum is
inserted into her vagina and opened, and the cervix
is cleansed with an antiseptic. Using ultrasound
(a device which uses sound waves to visualize internal
881

Chorionic villus sampling

Small, Eric J., and Frank M. Torti. ‘‘The Testes.’’ In Clinical
Oncology, edited by Martin D. Abeloff, et al., 2nd ed.
Philadelphia: Churchhill Livingstone, 2000.
Smithson, William A. ‘‘Gonadal and Germ Cell
Neoplasms.’’ In Nelson Textbook of Pediatrics, edited
by Richard E. Behrman, et al., 16th ed. Philadelphia:
W.B. Saunders, 2000.
Thigpen, James Tate. ‘‘Ovaries and Fallopian Tubes.’’ In
Clinical Oncology, edited by Martin D. Abeloff, et al.,
2nd ed. Philadelphia: Churchill Livingstone, 2000.

Chorionic villus sampling

Ultrasound transducer
Bladder

Chorionic villi

Amniotic fluid

Fetus (8-10 weeks)
Catheter

Uterine cavity

Vagina

Chorionic villus sampling is performed on pregnant women who are at risk for carrying a fetus with a genetic or chromosomal
defect. This procedure can be performed through the vagina and the cervix (transcervically) or through the abdomen (transabdominally). In the transcervical procedure, as depicted above, the physician uses ultrasound to help guide a catheter through
the cervix into the uterus. By applying suction from the syringe attached to the other end of the catheter, a small sample of the
chorionic villi are obtained. (Illustration by Electronic Illustrators Group.)

organs) as a guide, the doctor inserts a thin, plastic
tube called a catheter through the cervix and into the
uterus. The passage of the catheter through the cervix
may cause cramping. The doctor carefully watches
the image produced by the ultrasound and advances
the catheter to the chorionic villi. By applying suction
from the syringe attached to the other end of the
catheter, a small sample of the chorionic villi are
obtained. A cramping or pinching feeling may be
felt as the sample is being taken. The catheter is
then easily withdrawn.
For the transabdominal method, the woman lies
on her back on an examining table. Ultrasound
enables the doctor to locate the placenta. The specific
area on the woman’s abdomen is cleansed thoroughly
with an antiseptic and a local anesthetic may be
injected to numb the area. With ultrasound guidance,
a long needle is inserted through the woman’s abdominal wall, through the uterine wall and to the chorionic
villi. The sample is obtained by applying suction from
the syringe.

At the laboratory, the sample is examined under the
microscope and any contaminating cells or material is
carefully removed. The villi can be analyzed immediately, or incubated for a day or more to allow for cell
division. The cells are stopped in the midst of cell
division and spread onto a microscope slide. Cells
with clearly separated chromosomes are photographed so that the type and number of chromosomes
can be analyzed. Chromosomes are strings of DNA
which have been tightly compressed. Humans have 23
pairs of chromosomes including the sex chromosomes.
Rearrangements of the chromosomes or the presence
of additional or fewer chromosomes can be identified
by examination of the photograph. Down syndrome,
for instance, is caused by an extra copy of chromosome 21. In addition to the chromosomal analysis,
specialized tests can be performed as needed to look
for specific diseases such as Tay-Sachs disease.
Depending upon which tests are performed, results
may be available as early as two days or up to eight
days after the procedure.

The chorionic villus sample is immediately placed
into nutrient medium and sent to the laboratory.

Chorionic villus sampling costs between $1,200
and $1,800. Insurance coverage for this test may vary.

882

GALE ENCYCLOPEDIA OF MEDICINE

There are alternate procedures for diagnosing
genetic and chromosomal disorders of the fetus.
Amniocentesis is commonly used and involves inserting a needle through the pregnant woman’s abdomen
to obtain a sample of amniotic fluid. Amniocentesis is
usually performed in the second trimester at approximately 16 weeks gestation and the laboratory analysis may take two to three weeks. The two advantages
of chorionic villus sampling are that it is performed
during the first trimester and the results are available
in about one week. However, as of 1997, amniocentesis is being performed in the first trimester, but this is
still very rare. The risk of miscarriage after amniocentesis is 0.5–1% (one to two women out of 200)
which is lower than that for chorionic villus sampling
(1–3%).
A noninvasive alternative is the maternal blood
test called triple marker screening or multiple marker
screening. A sample of the pregnant woman’s blood is
analyzed for three different markers: alphafetoprotein
(AFP), human chorionic gonadotropin, and unconjugated estriol. The levels of these three markers in the
mother’s blood can identify unborn babies who are at
risk for certain genetic or chromosomal defects. This is
a screening test which determines the chance that the
fetus has the defect, but it can not diagnose defects.
A negative test result does not necessarily mean the
unborn baby does not have a birth defect. For
instance, this screening test can only predict 60–70%
of the fetuses with Down syndrome. Pregnant women
who have a positive triple marker screen are encouraged to undergo a diagnostic test, such as amniocentesis (by the time an AFP is done, it is too late to
perform a CVS).

Preparation
Prior to the chorionic villus sampling procedure
the woman needs to drink fluids and refrain from
urinating to ensure her bladder is full. These preparations create a better ultrasound picture.

Aftercare
It is generally recommended that women undergoing chorionic villus sampling have someone drive
them home and have no plans for the rest of the day.
Women with Rh negative blood must receive a Rho
(D) immune globulin injection following the procedure. Women should call their doctor if they experience excessive bleeding, vaginal discharge, fever, or
abdominal pain after the procedure.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Chorionic villi—Microscopic, finger-like projections that emerge from the outer sac which surrounds the developing baby. Chorionic villi are of
fetal origin and eventually form the placenta.
Chromosomes—Human cells carry DNA in tightly
compressed rod-like structures called chromosomes. Humans have 23 pairs of chromosomes
including the sex chromosomes.
Down syndrome—A chromosomal disorder
caused by an extra copy or a rearrangement of
chromosome 21. Children with Down syndrome
have varying degrees of mental retardation and
may have heart defects.
Fetus—Term for an unborn baby after the eighth
week of pregnancy. Prior to seven weeks, it is
called an embryo.
Rh sensitization—A woman with a negative blood
type (Rh negative) who has produced antibodies
against her fetus with a positive blood type (Rh
positive). The mother’s body considered the fetal
blood cells a foreign object and mounted an
immune attack on it.
Ultrasound—A safe, painless procedure which
uses sound waves to visualize internal organs.
A wand that transmits and receives the sound
waves is moved over the woman’s abdomen and
internal organs can be seen on a video screen.

Risks
Of women who undergo transcervical chorionic villus sampling, one third experience minimal vaginal spotting and 7–10% experience vaginal bleeding. One out of
five women experience cramping following the procedure. Two to three women out of 100 (or 2–3%) will
miscarry following chorionic villus sampling. The risk of
infection is very low. Rupture of the amniotic membranes is a rare complication. Women with Rh negative
blood may be at an increased risk for developing Rh
incompatibility following chorionic villus sampling.
There have been reports of limb defects in babies
following chorionic villus sampling. However, in 1996
the World Health Organization reported that the incidence of babies born with limb defects from 138,966
women who had undergone chorionic villus sampling
was the same as for women who had not. Therefore,
this study found no connection between chorionic
villus sampling and limb defects.
883

Chorionic villus sampling

Alternate procedures

Chronic fatigue syndrome

Normal results

Description

No genetic, chromosomal, or biochemical abnormalities were found in the fetal cells. The gender of the
fetus will be identified but will be made known to the
parents only with their approval.

Abnormal results
Analysis of the cells from the chorionic villus
enables the detection of over 200 diseases and disorders
such as Down Syndrome, Tay-Sachs disease, and cystic
fibrosis. Gross rearrangements of the chromosomes
and chromosome additions or losses are detected.
Resources
ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914) 4287100. resourcecenter@modimes.org. <http://
www.modimes.org>.
OTHER

Family Internet Page. <http://www.familyinternet.com>.

Belinda Rowland, PhD

Choroiditis see Uveitis
Choroiretinitis see Uveitis
Chromosome studies see Genetic testing
Chronic arthritis of childhood see Juvenile
arthritis
Chronic constrictive pericarditis see
Pericarditis
Chronic Epstein-Barr virus see Chronic
fatigue syndrome

I Chronic fatigue syndrome

CFS is the most common name for this disorder,
but it also has been called chronic fatigue and immune
disorder (CFIDS), myalgic encephalomyelitis, low
natural killer cell disease, post-viral syndrome,
Epstein-Barr disease, and Yuppie flu. CFS has so
many names because researchers have been unable to
find out exactly what causes it and because there are
many similar, overlapping conditions. Reports of a
CFS-like syndrome called neurasthenia date back to
1869. Later, people with similar symptoms were said
to have fibromyalgia because one of the main symptoms is myalgia, or muscle pain. Because of the similarity of symptoms, fibromyalgia and CFS are
considered to be overlapping syndromes.
In the early to mid-1980s, there were outbreaks
of CFS in some areas of the United States. Doctors
found that many people with CFS had high levels of
antibodies to the Epstein-Barr virus (EBV), which
causes mononucleosis, in their blood. For a while
they thought they had found the culprit, but it turned
out that many healthy people also had high EBV
antibodies. Scientists have also found high levels of
other viral antibodies in the blood of people with
CFS. These findings have led many scientists to
believe that a virus or combination of viruses may
trigger CFS.
CFS was sometimes referred to as Yuppie flu
because it seemed to often affect young, middle-class
professionals. In fact, CFS can affect people of any
gender, age, race, or socioeconomic group. Although
anyone can get CFS, most patients diagnosed with
CFS are 25–45 years old, and about 80% of cases are
in women. Estimates of how many people are afflicted
with CFS vary due to the similarity of CFS symptoms
to other diseases and the difficulty in identifying it.
The Centers for Disease Control and Prevention
(CDC) has estimated that four to 10 people per
100,000 in the United States have CFS. According to
the CFIDS Foundation, about 500,000 adults in the
United States (0.3% of the population) have CFS.
This probably is a low estimate since these figures do
not include children and are based on the CDC definition of CFS, which is very strict for research purposes.

Definition
Chronic fatigue syndrome (CFS) is a condition
that causes extreme tiredness. People with CFS have
debilitating fatigue that lasts for six months or longer.
They also have many other symptoms. Some of these
are pain in the joints and muscles, headache, and sore
throat. CFS does not have a known cause, but appears
to result from a combination of factors.
884

Causes and symptoms
There is no single known cause for CFS. Studies
have pointed to several different conditions that might
be responsible. These include:


viral infections



chemical toxins
GALE ENCYCLOPEDIA OF MEDICINE

allergies



trouble concentrating



immune abnormalities



memory loss



psychological disorders

A recent study at Johns Hopkins University found
an abnormality in blood pressure regulation in 22 of
23 patients with CFS. This abnormality, called neurally mediated hypotension, causes a sudden drop in
blood pressure when a person has been standing, exercising or exposed to heat for a while. When this occurs,
patients feel lightheaded and may faint. They often are
exhausted for hours to days after one of these episodes. When treated with salt and medications to stabilize blood pressure, many patients in the study had
marked improvements in their CFS symptoms.

Although the cause is still controversial, many doctors and researchers now think that CFS may not be a
single illness. Instead, they think CFS may be a group
of symptoms caused by several conditions. One theory
is that a microorganism, such as a virus, or a chemical
injures the body and damages the immune system,
allowing dormant viruses to become active. About
90% of all people have a virus in the herpes family
dormant (not actively growing or reproducing) in
their bodies since childhood. When these viruses start
growing again, the immune system may overreact and
produce chemicals called cytokines that can cause flulike symptoms. Immune abnormalities have been found
in studies of people with CFS, although the same
abnormalities are also found in people with allergies,
autoimmune diseases, cancer, and other disorders.
The role of psychological problems in CFS is very
controversial. Because many people with CFS are
diagnosed with depression and other psychiatric disorders, some experts conclude that the symptoms of
CFS are psychological. However, many people with
CFS did not have psychological disorders before getting the illness. Many doctors think that patients
become depressed or anxious because of the effects
of the symptoms of their CFS. One recent study concluded that depression was the result of CFS and was
not its cause.
Having CFS is not just a matter of being tired.
People with CFS have severe fatigue that keeps them
from performing their normal daily activities. They
find it difficult or impossible to work, attend school,
or even to take part in social activities. They may have
sleep disturbances that keep them from getting enough
rest or they may sleep too much. Many people with
CFS feel just as tired after a full night’s sleep as before
they went to bed. When they exercise or try to be active
in spite of their fatigue, people with CFS experience
what some patients call ‘‘payback’’–debilitating
exhaustion that can confine them to bed for days.
Other symptoms of CFS include:


muscle pain (myalgia)



joint pain (arthralgia)



sore throat



headache



fever and chills



tender lymph nodes

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
CFS is diagnosed by evaluating symptoms and
eliminating other causes of fatigue. Doctors carefully
question patients about their symptoms, any other illnesses they have had, and medications they are taking.
They also conduct a physical examination, neurological
examination, and laboratory tests to identify any
underlying disorders or other diseases that cause fatigue. In the United States, many doctors use the CDC
case definition to determine if a patient has CFS.
To be diagnosed with CFS, patients must meet
both of the following criteria:


Unexplained continuing or recurring chronic fatigue
for at least six months that is of new or definite onset,
is not the result of ongoing exertion, and is not
mainly relieved by rest, and causes occupational,
educational, social, or personal activities to be
greatly reduced.



Four or more of the following symptoms: loss of
short-term memory or ability to concentrate; sore
throat; tender lymph nodes; muscle pain; multijoint pain without swelling or redness; headaches of
a new type, pattern, or severity; unrefreshing sleep;
and post-exertional malaise (a vague feeling of discomfort or tiredness following exercise or other physical or mental activity) lasting more than 24 hours.
These symptoms must have continued or recurred
during six or more consecutive months of illness
and must not have started before the fatigue began.

Treatment
There is no cure for CFS, but many treatments are
available to help relieve the symptoms. Treatments
usually are individualized to each person’s particular
symptoms and needs. The first treatment most doctors
recommend is a combination of rest, exercise, and a
885

Chronic fatigue syndrome



Chronic fatigue syndrome

balanced diet. Prioritizing activities, avoiding overexertion, and resting when needed are key to maintaining
existing energy reserves. A program of moderate exercise helps to keep patients from losing physical conditioning, but too much exercise can worsen fatigue and
other CFS symptoms. Counseling and stress reduction
techniques also may help some people with CFS.
Many medications, nutritional supplements, and
herbal preparations have been used to treat CFS.
While many of these are unproven, others seem to
provide some people with relief. People with CFS
should discuss their treatment plan with their doctors,
and carefully weigh the benefits and risks of each
therapy before making a decision.
Drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs),
such as ibuprofen and naproxen, may be used to
relieve pain and reduce fever. Another medication
that is prescribed to relieve pain and muscle spasms is
cyclobenzaprine (sold as Flexeril).
Many doctors prescribe low dosages of antidepressants for their sedative effects and to relieve symptoms
of depression. Antianxiety drugs, such as benzodiazepines or buspirone may be prescribed for excessive
anxiety that has lasted for at least six months.
Other medications that have been tested or are
being tested for treatment of CFS are:


Fludrocortisone (Florinef), a synthetic steroid, which
is currently being tested for treatment of people with
CFS. It causes the body to retain salt, thereby increasing blood pressure. It has helped some people with
CFS who have neurally mediated hypotension.



Beta-adrenergic blocking drugs, often prescribed for
high blood pressure. Such drugs, including atenolol
(Tenoretic, Tenormin) and propranolol (Inderal),
are sometimes prescribed for neurally mediated
hypotension.



Gamma globulin, which contains human antibodies
to a variety of organisms that cause infection. It has
been used experimentally to boost immune function
in people with CFS.



Ampligen, a drug which stimulates the immune system
and has antiviral activity. In one small study, ampligen
improved mental function in people with CFS.

Alternative treatment
A variety of nutritional supplements are used for
treatment of CFS. Among these are vitamin C, vitamin
B12, vitamin A, vitamin E, and various dietary minerals.
886

KEY TERMS
Arthralgia—Joint pain.
Cytokines—Proteins produced by certain types of
lymphocytes. They are important controllers of
immune functions.
Depression—A psychological condition, with feelings of sadness, sleep disturbance, fatigue, and
inability to concentrate.
Epstein-Barr virus (EBV)—A virus in the herpes
family that causes mononucleosis.
Fibromyalgia—A disorder closely related to CFS.
Symptoms include pain, tenderness, and muscle
stiffness.
Lymph node—Small immune organs containing
lymphocytes. They are found in the neck, armpits,
groin, and other locations in the body.
Lymphocytes—White blood cells that are responsible for the actions of the immune system.
Mononucleosis—A flu-like illness caused by the
Epstein-Barr virus.
Myalgia—Muscle pain.
Myalgic encephalomyelitis—An older name for
chronic fatigue syndrome; encephalomyelitis refers
to inflammation of the brain and spinal cord.
Natural killer (NK) cell—A lymphocyte that acts as
a primary immune defense against infection.
Neurally mediated hypotension—A rapid fall in
blood pressure that causes dizziness, blurred
vision, and fainting, and is often followed by prolonged fatigue.
Neurasthenia—Nervous exhaustion–a disorder
with symptoms of irritability and weakness, commonly diagnosed in the late 1800s.

These supplements may help improve immune
and mental functions. Several herbs have been shown
to improve immune function and have other beneficial
effects. Some that are used for CFS are astragalus
(Astragalus membranaceus), echinacea (Echinacea
spp.), garlic (Allium sativum), ginseng (Panax ginseng),
gingko (Gingko biloba), evening primrose oil
(Oenothera biennis), shiitake mushroom extract
(Lentinus edodes), borage seed oil, and quercetin.
Many people have enhanced their healing process
for CFS with the use of a treatment program inclusive
of one or more alternative therapies. Stress reduction
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The course of CFS varies widely for different
people. Some people get progressively worse over
time, while others gradually improve. Some individuals have periods of illness that alternate with periods of good health. While many people with CFS
never fully regain their health, they find relief from
symptoms and adapt to the demands of the disorder
by carefully following a treatment plan combining
adequate rest, nutrition, exercise, and other therapies.

Prevention
Because the cause of CFS is not known, there
currently are no recommendations for preventing the
disorder.
Resources
ORGANIZATIONS

American Association for Chronic Fatigue Syndrome. 7 Van
Buren St., Albany, NY 12206. (518) 435-1765. <http://
weber.u.washington.edu/dedra/aacfs1.html>.
The CFIDS Association. Community Health Services, P.O.
Box 220398, Charlotte, NC 28222-0398. (704) 362-2343.
National CFIDS Foundation. 103 Aletha Road, Needham,
MA 02192. (781) 449-3535. <http://
www.cfidsfoundation.org>.
National CFS Association. 919 Scott Ave., Kansas City, KS
66105. (913) 321-2278.
OTHER

‘‘Chronic Fatigue Syndrome.’’ National Institutes of Health.
<http://www.nih.gov>.
‘‘The Facts about Chronic Fatigue Syndrome.’’ Centers
for Disease Control. <http://www.cdc.gov/ncidod/
diseases/cfs/facts1.htm>.

Toni Rizzo

granulomatous
I Chronic
disease
Definition
Chronic granulomatous disease (CGD) is an
inherited disorder in which white blood cells lose
their ability to destroy certain bacteria and fungi.
GALE ENCYCLOPEDIA OF MEDICINE

Description
CGD is an X-linked genetic disease, meaning the
defective gene is carried on the X chromosome (one of
the sex chromosomes). Females have two copies of the
X chromosome, whereas males have one X and one Y.
CGD also is a recessive defect meaning that both copies
of the chromosome must have the defect before it can
be expressed. Females who have one X chromosome
without the defect do not get this disease. Males, since
they only have one X chromosome, get the disease if the
defect is present. Thus, CGD affects mostly males.
CGD is an immunodeficiency disorder. Patients
with immunodeficiency disorders suffer frequent
infections. This happens because part of their immune
system isn’t working properly and the infectious
microorganisms are not killed as rapidly as is normal.
In CGD there is a defect in the ability of the white
blood cells to kill bacteria and fungi. The white blood
cells affected are phagocytic cells. They are part of the
non-specific immune system and move via the blood to
all parts of the body where they ingest and destroy
microbes. Phagocytic cells are the first line of defense
against microorganisms. In this disease, the decreased
ability to kill microbes that they have ingested leads to
a failure to effectively combat infectious diseases.
Patients with CGD are subject to certain types of
recurring infection, especially those of the skin,
lungs, mouth, nose, intestines, and lymph nodes.
With the exception of the lymph nodes, all of these
areas are considered external tissues that come into
contact with microorganisms from the environment.
The lymph system drains all areas of the body to
eliminate destroyed microorganisms and to assist the
immune system in attacking microorganisms.
Infections occur in the lymph nodes as a consequence
of the normal draining function.

Causes and symptoms
The genetic defect that causes CGD reduces the
amount of hydrogen peroxide and superoxide that
white blood cells can make. These chemicals are
important for killing bacteria and fungi. Without
them the white blood cells ingest the microorganisms,
but cannot kill them. In some cases, the microbes then
replicate inside the white blood cell eventually causing
its death.
Symptoms of the disease usually appear by age
two. Frequent, recurrent infections of the skin, lungs
(e.g. pneumonia), mouth (e.g. gingivitis), nose, intestines and lymph nodes are a hallmark of this disease.
Patients may also develop multiple, recurrent liver
abscesses and bone infections (osteomyelitis).
887

Chronic granulomatous disease

techniques such as biofeedback, meditation, acupuncture, and yoga may help people with sleep disturbances
relax and get more rest. They also help some people
reduce depression and anxiety caused by CFS.

Chronic kidney failure

KEY TERMS

National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Immunodeficiency—A weakening of the body’s
immune system.
Phagocytic cells—A cell that ingests microorganisms and foreign particles.

John T. Lohr, PhD

I Chronic kidney failure
Diagnosis
Diagnosis is made based on the observation of a
pattern of recurrent infections. Blood tests of lymphocyte and antibody functions will be normal. Tests of
phagocytic cells will show normal ingestion, but a
greatly decreased ability to kill bacteria.

Definition
Chronic kidney failure occurs when disease or
disorder damages the kidneys so that they are no
longer capable of adequately removing fluids and
wastes from the body or of maintaining the proper
level of certain kidney-regulated chemicals in the
bloodstream.

Treatment
Early, aggressive treatment of all infections is critical to the successful management of CGD. Patients
are treated with antibiotics and immune serum.
Antibiotics are used at the first sign of infection.
Immune serum is a source of antibodies that help
fight infections. Interferon gamma is an experimental
treatment for CGD that has shown promising results.
There is no cure for the underlying cause of chronic
granulomatous disease

Prognosis
Although antibiotics can treat most infections and
may help prevent others, premature death may result,
typically due to repeated lung infections.

Description
Chronic kidney failure, also known as chronic
renal failure, affects over 250,000 Americans annually.
It is caused by a number of diseases and inherited
disorders, but the progression of chronic kidney failure is always the same. The kidneys, which serve as the
body’s natural filtration system, gradually lose their
ability to remove fluids and waste products (urea)
from the bloodstream. They also fail to regulate certain chemicals in the bloodstream, and deposit protein
into the urine. Chronic kidney failure is irreversible,
and will eventually lead to total kidney failure, also
known as end-stage renal disease (ESRD). Without
proper treatment intervention to remove wastes and
fluids from the bloodstream, ESRD is fatal.

Causes and symptoms

Prevention
Since CGD is a hereditary disorder, it cannot
currently be prevented. Patients and their families
may benefit from genetic counseling. Preventive (prophylactic) antibiotics may help keep some infections
from occurring, and good hygiene, especially rigorous skin and mouth care, can help prevent infections
in these areas. Avoiding crowds or other people
who have infections are also effective preventive
measures.

Kidney failure is triggered by disease or a hereditary disorder in the kidneys. Both kidneys are typically
affected. The four most common causes of chronic
kidney failure include:


Diabetes. Diabetes mellitus (DM), both insulin
dependant (IDDM) and non-insulin dependant
(NIDDM), occurs when the body cannot produce
and/or use insulin, the hormone necessary for the
body to process glucose. Long-term diabetes may
cause the glomeruli, the filtering units located in the
nephrons of the kidneys, to gradually lose
functioning.



Glomerulonephritis. Glomerulonephritis is a chronic
inflammation of the glomeruli, or filtering units of
the kidney. Certain types of glomerulonephritis are

Resources
ORGANIZATIONS

Chronic Granulomatous Disease Association. 2616
Monterey Road, San Marino, CA 91108–1646. (818)
441–4118.

888

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Headaches. High blood pressure may trigger
headaches.

Hypertension. High blood pressure is unique in that it
is both a cause and a major symptom of kidney failure. The kidneys can become stressed and ultimately
sustain permanent damage from blood pushing
through them at an excessive level of pressure over
a long period of time.



Hypertension, or high blood pressure. The retention
of fluids and wastes causes blood volume to increase,
which in turn, causes blood pressure to rise.



Increased fatigue. Toxic substances in the blood and
the presence of anemia may cause feelings of
exhaustion.



Itching. Phosphorus, which is typically eliminated in
the urine, accumulates in the blood of patients with
kidney failure. This heightened phosphorus level
may cause itching of the skin.



Lower back pain. Pain where the kidneys are located,
in the small of the back below the ribs.



Nausea, loss of appetite, and vomiting. Urea in the
gastric juices may cause upset stomach. This can lead
to malnutrition and weight loss.

Polycystic kidney disease. Polycystic kidney disease is
an inherited disorder that causes cysts to be formed
on the nephrons, or functioning units, of the kidneys.
The cysts hamper the regular functioning of the
kidney.

Other possible causes of chronic kidney failure
include kidney cancer, obstructions such as kidney
stones, pyelonephritis, reflux nephropathy, systemic
lupus erythematosus, amyloidosis, sickle cell anemia,
Alport syndrome, and oxalosis.
Initially, symptoms of chronic kidney failure
develop slowly. Even individuals with mild to moderate kidney failure may show few symtpoms in spite of
increased urea in their blood. Among the symptoms
that may be present at this point are frequent urination
during the night and high blood pressure.
Most symptoms of chronic kidney failure are not
apparent until kidney disease has progressed significantly. Common symptoms include:


Anemia. The kidneys are responsible for the production of erythropoietin (EPO), a hormone which stimulates red cell production. If kidney disease causes
shrinking of the kidney, this red blood cell production is hampered.



Bad breath or a bad taste in mouth. Urea, or waste
products, in the saliva may cause an ammonia-like
taste in the mouth.



Bone and joint problems. The kidneys produce vitamin D, which aids in the absorption of calcium and
keeps bones strong. For patients with kidney failure,
bones may become brittle, and in the case of children,
normal growth may be stunted. Joint pain may also
occur as a result of unchecked phosphate levels in the
blood.



Edema. Puffiness or swelling around the eyes, arms,
hands, and feet.



Frequent urination.



Foamy or bloody urine. Protein in the urine may
cause it to foam significantly. Blood in the urine
may indicate bleeding from diseased or obstructed
kidneys, bladder, or ureters.

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Kidney failure is typically diagnosed and treated
by a nephrologist, a doctor that specializes in treating
the kidneys. The patient that is suspected of having
chronic kidney failure will undergo an extensive blood
work-up. A blood test will assess the levels of creatinine, blood urea nitrogen (BUN), uric acid, phosphate, sodium, and potassium in the blood. Urine
samples will also be collected, usually over a 24-hour
period, to assess protein loss.
Uncovering the cause of kidney failure is critical to
proper treatment. A full assessment of the kidneys is
necessary to determine if the underlying disease is treatable and if the kidney failure is chronic or acute. An
x ray, MRI, computed tomography scan, ultrasound,
renal biopsy, and/or arteriogram of the kidneys may be
employed to determine the cause of kidney failure and
level of remaining kidney function. X rays and ultrasound of the bladder and/or ureters may also be taken.

Treatment
Chronic kidney failure is an irreversible condition.
Hemodialysis, peritoneal dialysis, or kidney transplantation must be employed to replace the lost function of
the kidneys. In addition, dietary changes and treatment
to relieve specific symptoms such as anemia and high
blood pressure are critical to the treatment process.
Hemodialysis
Hemodialysis is the most frequently prescribed
type of dialysis treatment in the United States. Most
889

Chronic kidney failure



treatable, and may only cause a temporary disruption of kidney functioning.

Chronic kidney failure

hemodialysis patients require treatment three times a
week, for an average of three to four hours per dialysis
‘‘run’’ depending on the type of dialyzer used and their
current physical condition. The treatment involves
circulating the patient’s blood outside of the body
through an extracorporeal circuit (ECC), or dialysis
circuit. The dialysis circuit consists of plastic blood
tubing, a two-compartment filter known as a dialyzer,
or artificial kidney, and a dialysis machine that monitors and maintains blood flow and administers dialysate, a chemical bath used to draw waste products out
of the blood. The patient’s blood leaves and enters the
body through two needles inserted into the patient’s
vein, called an access site, and is pushed through the
blood compartment of the dialyzer. Once inside of the
dialyzer, excess fluids and toxins are pulled out of
the bloodstream and into the dialysate compartment,
where they are carried out of the body. At the same
time, electrolytes and other chemicals in the dialysate
solution move from the dialysate into the bloodstream. The purified, chemically-balanced blood is
then returned to the body.
Peritoneal dialysis
In peritoneal dialysis (PD), the patient’s peritoneum, or lining of the abdomen, acts as a blood filter.
A catheter is surgically inserted into the patient’s
abdomen. During treatment, the catheter is used to
fill the abdominal cavity with dialysate. Waste products and excess fluids move from the patient’s bloodstream into the dialysate solution. After a waiting
period of six to 24 hours, depending on the treatment
method used, the waste-filled dialysate is drained from
the abdomen, and replaced with clean dialysate.
There are three types of peritoneal dialysis, which
vary by treatment time and administration method:
Continuous Ambulatory Peritoneal Dialysis (CAPD),
Continuous Cyclic Peritoneal Dialysis (CCPD), and
Intermittent Peritoneal Dialysis (IPD).
Kidney transplantation
Kidney transplantation involves surgically attaching a functioning kidney, or graft, from a brain dead
organ donor (a cadaver transplant), or from a living
donor, to a patient with ESRD. Patients with chronic
renal disease who need a transplant and don’t have a
living donor register with UNOS (United Network for
Organ Sharing), the federal organ procurement
agency, to be placed on a waiting list for a cadaver
kidney transplant. Kidney availability is based on the
patient’s health status. When the new kidney is transplanted, the patient’s existing, diseased kidneys may or
may not be removed, depending on the circumstances
890

KEY TERMS
End-stage renal disease (ESRD)—Total kidney failure; chronic kidney failure is diagnosed as ESRD
when kidney function falls to 5-10% of capacity.
Nephrotic syndrome—Characterized by protein
loss in the urine, low protein levels in the blood,
and fluid retention.
Ureters—The two ducts that pass urine from each
kidney to the bladder.

surrounding the kidney failure. A regimen of immunosuppressive, or anti-rejection medication, is required
after transplantation surgery.
Dietary management
A diet low in sodium, potassium, and phosphorous, three substances that the kidneys regulate, is critical in managing kidney disease. Other dietary
restrictions, such as a reduction in protein, may be
prescribed depending on the cause of kidney failure
and the type of dialysis treatment employed. Patients
with chronic kidney failure also need to limit their
fluid intake.
Medications and dietary supplements
Kidney failure patients with hypertension typically take medication to control their high blood pressure. Epoetin alfa, or EPO (Epogen), a hormone
therapy, and intravenous or oral iron supplements
are used to manage anemia. A multivitamin may be
prescribed to replace vitamins lost during dialysis
treatments. Vitamin D, which promotes the absorption of calcium, along with calcium supplements, may
also be prescribed.
Since 1973, Medicare has picked up 80% of
ESRD treatment costs, including the costs of dialysis
and transplantation and of some medications. To qualify for benefits, a patient must be insured or eligible
for benefits under Social Security, or be a spouse or
child of an eligible American. Private insurance and
state Medicaid programs often cover the remaining
20% of treatment costs.

Prognosis
Early diagnosis and treatment of kidney failure is
critical to improving length and quality of life in
chronic kidney failure patients. Patient outcome varies
GALE ENCYCLOPEDIA OF MEDICINE

The demand for kidneys to transplant continues
to exceed supply. In 1996, over 34,000 Americans were
on the UNOS waiting list for a kidney transplant, but
only 11,330 living donor and cadaver transplants were
actually performed. Cadaver kidney transplants have
a 50% chance of functioning nine years, and living
donor kidneys that have two matching antigen pairs
have a 50% chance of functioning for 24 years.
However, some transplant grafts have functioned for
over 30 years.
Resources
ORGANIZATIONS

American Association of Kidney Patients. 100 S. Ashley
Drive, #280, Tampa, FL 33602. (800) 749-2257.
<http://www.aakp.org>.
American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://www.arbon.com/kidney>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.
United States Renal Data System (USRDS). The University
of Michigan, 315 W. Huron, Suite 240, Ann Arbor, MI
48103. (734) 998-6611. <http://www.med.umich.edu/
usrds>.

Paula Anne Ford-Martin

Chronic leukemias see Leukemias, chronic

obstructive lung
I Chronic
disease
Definition
Chronic obstructive lung disease, also known as
chronic obstructive pulmonary disease (COPD), is a
general term for a group of conditions in which there is
persistent difficulty in expelling (or exhaling) air from
the lungs. COPD commonly refers to two related,
progressive diseases of the respiratory system, chronic
bronchitis and emphysema. Because smoking is the
major cause of both diseases, chronic bronchitis and
emphysema often occur together in the same patient.
GALE ENCYCLOPEDIA OF MEDICINE

Description
COPD is one of the fastest-growing health problems. Nearly 16 million people in the United States,
14 million with chronic bronchitis and two million with
emphysema, suffer from COPD. COPD is responsible
for more than 96,000 deaths annually, making it the
fourth leading cause of death. Although COPD is more
common in men than women, the increase in incidence
of smoking among women since World War II has
produced an increase in deaths from COPD in
women. COPD has a large economic impact on the
healthcare system and a destructive impact on the
lives of patients and their families. Quality of life for a
person with COPD decreases as the disease progresses.
Chronic bronchitis
In chronic bronchitis, chronic inflammation
caused by cigarette smoking results in a narrowing of
the openings in the bronchi, the large air tubes of the
respiratory system, and interferes with the flow of air.
Inflammation also causes the glands that line the
bronchi to produce excessive amounts of mucus,
further narrowing the airways and blocking airflow.
The result is often a chronic cough that produces sputum (mainly mucus) and shortness of breath. Cigarette
smoke also damages the cilia, small hair-like projections that move bacteria and foreign particles out of
the lungs, increasing the risk of infections.
Emphysema
Emphysema is a disease in which cigarette smoke
causes an overproduction of the enzyme elastase, one
of the immune system’s infection-fighting biochemicals. This results in irreversible destruction of a protein in the lung called elastin which is important for
maintaining the structure of the walls of the alveoli,
the terminal small air sacs of the respiratory system.
As the walls of the alveoli rupture, the number of
alveoli is reduced and many of those remaining are
enlarged, making the lungs of the patient with emphysema less elastic and overinflated. Due to the higher
pressure inside the chest that must be developed to
force air out of the less-elastic lungs, the bronchioles,
small air tubes of the respiratory system, tend to collapse during exhalation. Stale air gets trapped in the
air sacs and fresh air cannot be brought in.

Causes and symptoms
There are several important risk factors for COPD:


Lifestyle. Cigarette smoking is by far the most important risk factor for COPD (80% of all cases). Cigar
891

Chronic obstructive lung disease

by the cause of chronic kidney failure and the method
chosen to treat it. Overall, patients with chronic kidney disease leading to ESRD have a shortened lifespan. According to the United States Renal Data
System (USRDS), the lifespan of an ESRD patient is
18–47% of the lifespan of the age-sex-race matched
general population. ESRD patients on dialysis have a
lifespan that is 16–37% of the general population.

Chronic obstructive lung disease

and pipe smoking can also cause COPD. Air pollution and industrial dusts and fumes are other important risk factors.


Age. Chronic bronchitis is more common in people
over 40 years old; emphysema occurs more often in
people 65 years of age and older.



Socioeconomic class. COPD-related deaths are
about twice as high among unskilled and semi-skilled
laborers as among professionals.



Family clustering. It is thought that heredity predisposes people in certain families to the development of
COPD when other causes, such as smoking and air
pollution, are present.



Lung infections. Lung infections make all forms of
COPD worse.

In the general population, emphysema usually
develops in older individuals with a long smoking history. However, there is also a form of emphysema that
runs in families. People with this type of emphysema
have a hereditary deficiency of a blood component, an
enzyme inhibitor called alpha-1-antitrypsin (AAT).
This type of emphysema is sometimes called ‘‘early
onset emphysema’’ because it can appear when a person
is as young as 30 or 40 years old. It is estimated that
there are between 75,000 and 150,000 Americans who
were born with AAT-deficiency. Of this group, emphysema afflicts an estimated 20,000–40,000 people (1–3%
of all cases of emphysema). The risk of developing
emphysema for an AAT-deficient individual who also
smokes is much greater than for others.
The first symptoms of chronic bronchitis are cough
and mucus production. These symptoms resemble a
chest cold that lingers on for weeks. Later, shortness of
breath develops. Cough, sputum production, and shortness of breath may become worse if a person develops a
lung infection. A person with chronic bronchitis may
later develop emphysema as well. In emphysema, shortness of breath on exertion is the predominant early
symptom. Coughing is usually minor and there is little
sputum. As the disease progresses, the shortness of
breath occurs with less exertion, and eventually may
be present even when at rest. At this point, a sputumproducing cough may also occur. Either chronic bronchitis or emphysema may lead to respiratory failure–a
condition in which there occurs a dangerously low level
of oxygen or a serious excess of carbon dioxide in the
blood.

Diagnosis
The first step in diagnosing COPD is a good medical evaluation, including a medical history and a
892

physical examination of the chest using a stethoscope.
In addition, the doctor may request one or more of the
following tests:
Pulmonary function test
Using a spirometer, an instrument that measures
the air taken into and exhaled from the lungs, the
doctor will determine two important values: (1) vital
capacity (VC), the largest amount of air expelled after
the deepest inhalation, and (2) forced expiratory
volume (FEV1), the maximum amount of air expired
in one second. The pulmonary function test can be
performed in the doctor’s office, but is expensive.
Chest x ray
Chest x rays can detect only about half of the cases
of emphysema. Chest x rays are rarely useful for diagnosing chronic bronchitis.
Blood gas levels
Blood may be drawn from an artery (more painful
than drawing blood from a vein) to determine the
amount of oxygen and carbon dioxide present. Low
oxygen and high carbon dioxide levels are often indicative of chronic bronchitis, but not always of
emphysema.
Tests for cause of infection
If infection is present, blood and sputum tests may
be done to determine the cause of infection.
Electrocardiogram (ECG)
Many patients with lung disease also develop
heart problems. The ECG identifies signs of heart
disease.

Treatment
The precise nature of the patient’s condition will
determine the type of treatment prescribed for COPD.
With a program of complete respiratory care, disability can be minimized, acute episodes prevented, hospitalizations reduced, and some early deaths avoided.
On the other hand, no treatment has been shown to
slow the progress of the disease, and only oxygen
therapy increases survival rate.
Drugs
Medications frequently prescribed for COPD
patients include:
GALE ENCYCLOPEDIA OF MEDICINE

Chronic obstructive lung disease

A

B

C
D

A. Lung cancer. B. Pneumonia. C. Emphysema. D. Phlegm from chronic bronchitis. (Illustration by Argosy, Inc.)



Bronchodilators. These agents open narrowed airways
and offer significant symptomatic relief for many,
but not all, people with COPD. There are three types
of bronchodilators: Beta2 agonists, anticholinergic
agents, and theophylline and its derivatives.
Depending on the specific drug, a bronchodilator
may be inhaled, injected, or taken orally.



Corticosteroids. Corticosteroids, usually inhaled,
block inflammation and are most useful for patients
with chronic bronchitis with or without emphysema.
Steroids are generally not useful in patients who have
emphysema.



Oxygen replacement. Eventually, patients with low
blood oxygen levels may need to rely on supplemental oxygen from portable or stationary tanks.



Antibiotics. Antibiotics are frequently given at the
first sign of a respiratory infection, such as increased
sputum production or a change in color of sputum
from clear to yellow or green.



Vaccines. To prevent pulmonary infection from
viruses and bacteria, people with COPD should be
vaccinated against influenza each year at least six
weeks before flu season and have a one-time pneumococcal (pneumonia) vaccine.



Expectorants. These agents help loosen and expel
mucus secretions from the airways.



Diuretics. These drugs are given to prevent excess
water retention in patients with associated right
heart failure.

GALE ENCYCLOPEDIA OF MEDICINE



Augmentation therapy (for emphysema due to AATdeficiency only). Replacement AAT (Prolastin),
derived from human blood which has been screened
for viruses, is injected weekly or bimonthly for life.
Surgery

Surgical procedures for emphysema are very rare.
They are expensive and often not covered by insurance. The great majority of patients cannot be helped
by surgery, and no single procedure is ideal for those
who can be helped. In January of 1996, the government temporarily suspended Medicare payments for
lung reduction surgery.


Lung transplantation. Lung transplantation has been
successfully employed in some patients with endstage COPD. In the hands of an experienced team,
the one-year survival rate is over 70%.



Lung volume reduction. These procedures remove
20–30% of severely diseased lung tissue; the remaining parts of the lung are joined together. Mortality
rates can be as high as 15% and complication rates are
even higher. When the operation is successful, patients
report significant improvement in symptoms.
Pulmonary rehabilitation

A structured, outpatient pulmonary rehabilitation
program improves functional capacity in certain
patients with COPD. Services may include general
exercise training, administration of oxygen and nutritional supplements, intermittent mechanical ventilatory
893

Circumcision

KEY TERMS
Alpha-1-antitrypsin (AAT)—A blood component
that breaks down infection-fighting enzymes such
as elastase.
Alveoli—Terminal air sacs of the respiratory system, where gas (oxygen and carbon dioxide)
exchange occurs.
Bronchi—Large air tubes of the respiratory system.
Bronchioles—Small air tubes of the respiratory
system.
Bronchodilators—Drugs that open wider the bronchial tubes of the respiratory system.
Corticosteroids—A group of hormones that are
used as drugs to block inflammation.
Forced expiratory volume (FEV1)—The maximum
amount of air expired in one second.
Spirometer—An instrument used by a doctor to
perform a breathing test.
Vital capacity (VC)—The largest amount of air
expelled after one’s deepest inhalation.

infections, avoiding allergens, maintaining good nutrition, drinking lots of fluids, avoiding excessively low or
high temperatures and very high altitudes, maintaining
proper weight, and exercising to increase muscle tone.
Resources
PERIODICALS

Cordova, Francis C., and Gerard J. Griner. ‘‘Management
of Advanced Chronic Obstructive Pulmonary Disease.’’
Comprehensive Therapy 23, no. 6: 413-424.
Lefrak, Stephen S., et al. ‘‘Recent Advances in Surgery for
Emphysema.’’ Annual Review of Medicine 48: 387-398.
ORGANIZATIONS

American Association for Respiratory Care. 11030 Ables
Lane, Dallas, TX 75229. (214) 243-2272. <http://
www.aarc.org>.
American Lung Association. 1740 Broadway, New York, NY
10019. (800) 586-4872. <http://www.lungusa.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Jewish Medical and Research Center. 1400
Jackson St., Denver, CO 80206. (800) 222-LUNG
(Lung Line). <http://www.njc.org>.

Harry W. Golden
support, continuous positive airway pressure, relaxation techniques, breathing exercises and techniques
(such as pursed lip breathing), and methods for mobilizing and removing secretions.

Chronic obstructive pulmonary disease see
Emphysema; Chronic obstructive lung
disease
Churg-Strauss syndrome see Vasculitis

Alternative treatment
For both chronic bronchitis and emphysema,
alternative practitioners recommend diet and nutritional supplements, a variety of herbal medicines,
hydrotherapy, acupressure and acupuncture, aromatherapy, homeopathy, and yoga.

Prognosis
COPD is a disease that can be treated and controlled, but not cured. Survival of patients with COPD
is clearly related to the degree of their lung function
when they are diagnosed and the rate at which they lose
this function. Overall, the median survival is about 10
years for patients with COPD who have lost approximately two-thirds of their lung function at diagnosis.

Prevention
Lifestyle modifications that can help prevent
COPD, or improve function in COPD patients, include:
quitting smoking, avoiding respiratory irritants and
894

Cingulotomy see Psychosurgery
Ciprofloxacin see Fluoroquinolones
Circadian rhythm sleep disorders see Jet lag

I Circumcision
Definition
The surgical removal of the foreskin of the penis
or prepuce.

Purpose
In the United States, circumcision in infant boys is
performed for social, medical, or cultural/religious
reasons. Once a routine operation urged by pediatricians and obstetricians for newborns in the middle of
the twentieth century, circumcision has become an
elective option that parents make for their sons on an
GALE ENCYCLOPEDIA OF MEDICINE

Circumcision

Figure A

Figure B

Figure C

Figure D

A typical circumcision procedure involves the following steps: Figure A: The surgeon makes an incision around the foreskin.
Figure B: The foreskin is then freed from the skin covering the penile shaft. Figure C: The surgeon cuts the foreskin to the initial
incision, lifting the foreskin from the mucous membrane. Figure D: The surgeon sutures the top edge of the skin that covers the
penile shaft and the mucous membrane. (Illustration by Electronic Illustrators Group.)

individual basis. Families who practice Judaism or
Islam may select to have their sons circumcised as a
religious practice. Others choose circumcision for
medical benefits.
Female circumcision (also known as female genital mutilation) is usually performed for cultural and
social reasons by family members and others who are
not members of the medical profession, with no
anesthesia. Not only is the prepuce removed but
often the vaginal opening is sewn to make it smaller.
This practice is supposed to ensure the virginity of a
bride on her wedding day. It also prevents the woman
from achieving sexual pleasure during coitus. This
practice is not universally approved by the medical
profession and is considered by some as a human
rights violation.
Though the incidence of male circumcision has
decreased from 90% in 1979 to 60% in 1996, it is still
the most common surgical operation in the United
States. Circumcision rates are much lower for the
rest of the industrialized world. In Britain, it is only
done for religious practices or to correct a specific
medical condition of the penis.
Some of the medical reasons parents choose circumcision are to protect against infections of the urinary tract and the foreskin, prevent cancer, lower the
risk of getting sexually transmitted diseases, and
GALE ENCYCLOPEDIA OF MEDICINE

prevent phimosis (a tightening of the foreskin that
may close the opening of the penis). Though studies
indicate that uncircumcised boys under the age of five
are 20 times more likely than circumcised boys to have
urinary tract infections (UTIs), the rate of incidence of
UTIs is quite low. There are also indications that
circumcised men are less likely to suffer from penile
cancer, inflammation of the penis, or have many sexually transmitted diseases. Here again, the rate of incidence is low. Good hygiene usually prevents most
infections of the penis. Phimosis and penile cancer
are very rare, even in men who have not been circumcised. Education and good safe sex practices can prevent sexually transmitted diseases in ways that a
surgical procedure cannot because these are diseases
acquired through risky behaviors.
With these factors in mind, the American Academy
of Pediatrics has issued a policy statement that states
though there is existing scientific evidence that indicates
the medical benefits of circumcision, the benefits are
not strong enough to recommended circumcision as a
routine practice.

Precautions
Circumcision should not be performed on infants
with certain deformities of the penis that may require a
portion of the foreskin for repair. The most common
895

Circumcision

KEY TERMS
Foreskin—A covering fold of skin over the tip of the
penis.
Glans—The cone-shaped tip of the penis.

A

B

A. uncircumcised penis. B. circumcised penis. (Illustration by
Argosy Inc.)

condition for surgery using the foreskin is hypospadias, a congenital deformity of the penis where the
urinary tract opening is not at the tip of the glans.
Also, infants with a large hydrocoele or hernia may
suffer important complications through circumcision.
Premature infants and infants with serious infections
are also poor candidates to be circumcised, as are
infants with hemophilia, other bleeding disorders, or
whose mothers had taken anticoagulant drugs. In older
boys or men, circumcision is a minor procedure.
Therefore, it can be performed in virtually anyone
without a serious illness or unusual deformity.

Description
The foreskin of the penis protects the sensitivity of
the glans and shields it from irritation by urine, feces,
and foreign materials. It also protects the urinary
opening against infection and incidental injury.
In circumcision of infants, the foreskin is pulled
tightly into a specially designed clamp, and the foreskin pulls away from the broadened tip of the penis.
Pressure from the clamp stops bleeding from blood
vessels that supplied the foreskin. In older boys or
adults, an incision is made around the base of the
foreskin, the foreskin is pulled back, and then it is
cut away from the tip of the penis. Stitches are usually
used to close the skin edges.

Preparation
Despite a long-standing belief that infants do not
experience serious pain from circumcision, most
authorities now believe that some form of local
anesthesia is necessary. The physician injects local
anesthesia at the base of the penis or under the skin
around the penis (subcutaneous ring block). Both
anesthetics block key nerves. EMLA cream, a topical
formula of several anesthetics can also be used.
896

Hernia—Bulging of abdominal structures through
an abnormal opening in the muscular wall.
Hydrocele—Collection of fluid in the scrotum.
Hypospadias—A congenital deformity of the penis
where the urinary tract opening is not at the tip of
the glans.
Phimosis—A tightening of the foreskin that may
close the opening of the penis.
Prepuce—A fold like the foreskin that covers the
clitoris; another name for foreskin.

Aftercare
After circumcision, the wound should be washed
daily. An antibiotic ointment or petroleum jelly may
be applied to the site. If there is an incision, a wound
dressing will be present and should be changed each
time the diaper is changed. Sometimes a plastic ring is
used instead of a bandage. The ring will usually fall off
in five to eight days. The penis will heal in seven to 10
days.
Infants who undergo circumcision may be fussy
for some hours afterward, so parents should be prepared for crying, feeding problems, and sleep problems. Generally these go away within a day. In
older boys, the penis may be painful, but this will go
away gradually. A topical anesthetic ointment or
spray may be used to relieve this temporary discomfort. There may also be a ‘‘bruise’’ on the penis, which
typically goes away with no particular attention.

Risks
Complications following newborn circumcision
appear in one out of every 500 procedures. Most complications are minor. Bleeding occurs in half of
the complications and is usually easy to control.
Infections are rare and present with fever and signs
of inflammation.
There may be injuries to the penis itself, and these
may be difficult to repair. In 2000, there were reports
that the surgical clamps used in circumcision were at
fault in over 100 injuries reported between July 1996
GALE ENCYCLOPEDIA OF MEDICINE

Resources

Cirrhosis is the seventh leading cause of diseaserelated death in the United States. It is the third most
common cause of death in adults between the ages of
45 and 65. It is twice as common in men as in women.
The disease occurs in more than half of all malnourished chronic alcoholics, and kills about 25,000 people
a year. In Asia and Africa, however, most deaths from
cirrhosis are due to chronic hepatitis B.

BOOKS

Gollaher, David L. Circumcision: A History of the World’s
Most Controversial Surgery. Basic Books, 2000.
PERIODICALS

Imperio, Winnie Anne. ‘‘Circumcision Appears Safe, But
Not Hugely Beneficial.’’ OB GYN News 35, no. 7
(April 1, 2000): 9.
Schmitt, B. D. ‘‘The Circumcision Decision: Pros and
Cons.’’ Clinical Reference Systems 2000: 1579.
OTHER

American Academy of Pediatrics. New AAP Circumcision
Policy Released (Press Release). March 1, 1999.
<http://www.aap.org/advocacy/archives/
marcircum.htm>.

Janie F. Franz

I Cirrhosis
Definition
Cirrhosis is a chronic degenerative disease in
which normal liver cells are damaged and are then
replaced by scar tissue.

Description
Cirrhosis changes the structure of the liver and the
blood vessels that nourish it. The disease reduces the
liver’s ability to manufacture proteins and process
hormones, nutrients, medications, and poisons.
Cirrhosis gets worse over time and can become
potentially life threatening. This disease can cause:


excessive bleeding (hemorrhage)



impotence



liver cancer



coma due to accumulated ammonia and body wastes
(liver failure)



sepsis (blood poisoning)



death

GALE ENCYCLOPEDIA OF MEDICINE

Types of cirrhosis
Portal or nutritional cirrhosis is the form of
the disease most common in the United States.
About 30–50% of all cases of cirrhosis are this type.
Nine out of every 10 people who have nutritional
cirrhosis have a history of alcoholism. Portal or nutritional cirrhosis is also called Laënnec’s cirrhosis.
Biliary cirrhosis is caused by intrahepatic bileduct diseases that impede bile flow. Bile is formed in
the liver and is carried by ducts to the intestines. Bile
then helps digest fats in the intestines. Biliary cirrhosis
can scar or block these ducts. It represents 15–20% of
all cirrhosis.
Various types of chronic hepatitis, especially
hepatitis B and hepatitis C, can cause postnecrotic
cirrhosis. This form of the disease affects up to 40%
of all patients who have cirrhosis.
Disorders like the inability to metabolize iron and
similar disorders may cause pigment cirrhosis (hemochromatosis), which accounts for 5–10% of all instances
of the disease.

Causes and symptoms
Long-term alcoholism is the primary cause of
cirrhosis in the United States. Men and women
respond differently to alcohol. Although most men
can safely consume two to five drinks a day, one or
two drinks a day can cause liver damage in women.
Individual tolerance to alcohol varies, but people who
drink more and drink more often have a higher risk of
developing cirrhosis. In some people, one drink a day
can cause liver scarring.
Chronic liver infections, such as hepatitis B and
particularly hepatitis C, are commonly linked to cirrhosis. People at high risk of contracting hepatitis B
include those exposed to the virus through contact
with blood and body fluids. This includes healthcare
workers and intravenous (IV) drug users. In the past,
people have contracted hepatitis C through blood
transfusions. As of 2003, cirrhosis resulting from
chronic hepatitis has emerged as a leading cause of
death among HIV-positive patients; in Europe, about
897

Cirrhosis

and January 2000. In nearly all cases, the clamps were
assumed to be in working order but had been repaired
with replacement parts that were not of the manufacturer’s specifications. Physicians were urged to inspect
the clamps before use and ensure that their dimensions
fit their infant patients.

Cirrhosis

30% of HIV-positive patients are coinfected with a
hepatitis virus.
Liver injury, reactions to prescription medications, exposure to toxic substances, and repeated episodes of heart failure with liver congestion can cause
cirrhosis. The disorder can also be a result of diseases
that run in families (inherited diseases) like:


a lack of a specific liver enzyme (alpha1-antitrypsin
deficiency)



the absence of a milk-digesting enzyme (galactosemia)



an inability to convert sugars to energy (glycogen
storage disease)



an absorption deficit in which excess iron is deposited in the liver, pancreas, heart, and other organs
(hemochromatosis)



a disorder characterized by accumulations of copper
in the liver, brain, kidneys, and corneas (Wilson’s
disease)

Obesity has recently been recognized as a risk
factor in nonalcoholic hepatitis and cirrhosis. Some
surgeons are recommending as of 2003 that patients
scheduled for weight-reduction surgery have a liver
biopsy to evaluate the possibility of liver damage.
Poor nutrition increases a person’s risk of developing cirrhosis. In about 10 out of every 100 patients,
the cause of cirrhosis cannot be determined. Many
people who have cirrhosis do not have any symptoms
(often called compensated cirrhosis). Their disease is
detected during a routine physical or when tests for an
unrelated medical problem are performed. This type
of cirrhosis can also be detected when complications
occur (decompensated cirrhosis).
Symptoms of cirrhosis are usually caused by the
loss of functioning liver cells or organ swelling due to
scarring. The liver enlarges during the early stages of
illness. The palms of the hands turn red and patients
may experience:


constipation



diarrhea



dull abdominal pain



fatigue



indigestion



loss of appetite



nausea



vomiting



weakness



weight loss

898

As the disease progresses, the spleen enlarges and
fluid collects in the abdomen (ascites) and legs
(edema). Spider-like blood vessels appear on the
chest and shoulders, and bruising becomes common.
Men sometimes lose chest hair. Their breasts may
grow and their testicles may shrink. Women may
have menstrual irregularities.
Cirrhosis can cause extremely dry skin and intense
itching. The whites of the eyes and the skin may turn
yellow (jaundice), and urine may be dark yellow or
brown. Stools may be black or bloody. Sometimes
the patient develops persistent high blood pressure
due to the scarring (portal hypertension). This type of
hypertension can be life threatening. It can cause veins
to enlarge in the stomach and in the tube leading from
the mouth to the stomach (esophagus). These enlarged
veins are called varices, and they can rupture and bleed
massively.
Other symptoms of cirrhosis include:


anemia



bleeding gums



decreased interest in sex



fever



fluid in the lungs



hallucinations



lethargy



lightheadedness



muscle weakness



musty breath



painful nerve inflammation (neuritis)



slurred speech



tremors

If the liver loses its ability to remove toxins from
the brain, the patient may have additional symptoms.
The patient may become forgetful and unresponsive,
neglect personal care, have trouble concentrating, and
acquire new sleeping habits. These symptoms are
related to ammonia intoxication and the failure of
the liver to convert ammonia to urea. High protein
intake in these patients can also lead to these
symptoms.

Diagnosis
A patient’s medical history can reveal illnesses or
lifestyles likely to lead to cirrhosis. Liver changes can
be seen during a physical examination. A doctor who
suspects cirrhosis may order blood and urine tests to
GALE ENCYCLOPEDIA OF MEDICINE

Cirrhosis
A micrograph of a human liver showing tissue damaged by cirrhosis. (Photograph by Professor P. Motta, Photo Researchers, Inc.
Reproduced by permission.)

measure liver function. Because only a small number
of healthy cells are needed to carry out essential liver
functions, test results may be normal even when cirrhosis is present.
Computed tomography scans (CT), ultrasound,
and other imaging techniques can be used during diagnosis. They can help determine the size of the liver,
indicate healthy and scarred areas of the organ, and
detect gallstones. Cirrhosis is sometimes diagnosed
during surgery or by examining the liver with a laparoscope. This viewing device is inserted into the patient’s
body through a tiny incision in the abdomen.
Liver biopsy is usually needed to confirm a diagnosis of cirrhosis. In this procedure, a tissue sample is
removed from the liver and is examined under a microscope in order to learn more about the organ.
A newer and less invasive test involves the measurement of hyaluronic acid in the patient’s blood
serum. As of 2003, however, the serum hyaluronic
acid test is most useful in monitoring the progress of
liver disease; it is unlikely to completely replace liver
biopsy in the diagnosis of cirrhosis.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
The goal of treatment is to cure or reduce the
condition causing cirrhosis, prevent or delay disease
progression, and prevent or treat complications.
Salt and fluid intake are often limited, and activity
is encouraged. A diet high in calories and moderately
high in protein can benefit some patients. Tube feedings or vitamin supplements may be prescribed if the
liver continues to deteriorate. Patients are asked not to
consume alcohol.
Medication
Iron supplements, diuretics, and antibiotics may be
used for anemia, fluid retention, and ammonia accumulation associated with cirrhosis. Vasoconstrictors
are sometimes needed to stop internal bleeding and
antiemetics may be prescribed to control nausea.
Laxatives help the body absorb toxins and accelerate their removal from the digestive tract. Beta blockers may be prescribed to control cirrhosis-induced
portal hypertension. Because the diseased liver can no
899

Cirrhosis

longer efficiently neutralize harmful substances, medications must be given with caution. Interferon medicines may be used by patients with chronic hepatitis B
and hepatitis C to prevent post-hepatic cirrhosis.



seems confused or unresponsive



shows signs of infection (redness, swelling, tenderness, pain)

Alternative treatment

Surgery
Medication that causes scarring can be injected
directly into veins to control bleeding from varices in
the stomach or esophagus. Varices may require a special surgical procedure called balloon tamponade ligation to stop the bleeding. Surgery may be required to
repair disease-related throat damage. It is sometimes
necessary to remove diseased portions of the spleen
and other organs.
Liver transplants can benefit patients with
advanced cirrhosis. However, the new liver will eventually become diseased unless the underlying cause of
cirrhosis is removed. Patients with alcoholic cirrhosis
must demonstrate a willingness to stop drinking before
being considered suitable transplant candidates.
The incidence of liver cancer related to cirrhosis in
the United States has increased 75% since the early
1990s. Partial surgical removal of the liver in patients
with early-stage cancer of the liver appears to be as
successful as transplantation, in terms of the 5-year
survival rate.
Supportive measures

Alternative treatments for cirrhosis are aimed at
promoting the function of healthy liver cells and
relieving the symptoms associated with the disease.
Several herbal remedies may be helpful to cirrhosis
patients. Dandelion (Taraxacum officinale) and rockpoppy (Chelidonium majus) may help improve the efficiency of liver cells. Milk thistle extract (Silybum marianum) may slow disease progression and significantly
improve survival rates in alcoholics and other cirrhosis
patients. Practitioners of homeopathy and traditional
Chinese medicine can also prescribe treatments that
support healthy liver function.

Prognosis
Cirrhosis-related liver damage cannot be reversed,
but further damage can be prevented by patients who:


eat properly



get enough rest



do not consume alcohol



remain free of infection

A balanced diet promotes regeneration of healthy
liver cells. Eating five or six small meals throughout the
day should prevent the sick or bloated feeling patients
with cirrhosis often have after eating. Alcohol and
caffeine, which destroy liver cells, should be avoided.
So should any foods that upset the stomach. Patients
with brain disease associated with cirrhosis should
avoid excessive amounts of protein in the diet.

If the underlying cause of cirrhosis cannot be
corrected or removed, scarring will continue. The
liver will fail, and the patient will probably die within
five years. Patients who stop drinking after being diagnosed with cirrhosis can increase their likelihood of
living more than a few years from 40% to 60–70%.

A patient can keep a food diary that describes
what was eaten, when it was eaten, and how the
patient felt afterwards. This diary can be useful in
identifying foods that are hard to digest and in scheduling meals to coincide with the times the patient is
most hungry.

Eliminating alcohol abuse could prevent 75–80%
of all cases of cirrhosis.

Patients who have cirrhosis should weigh themselves every day and notify their doctor of a sudden
gain of five pounds or more. A doctor should also be
notified if symptoms of cirrhosis appear in anyone
who has not been diagnosed with the disease. A doctor
should also be notified if a patient diagnosed with
cirrhosis:


vomits blood



passes black stools

900

Prevention

Other preventive measures include:


obtaining counseling or other treatment for
alcoholism



taking precautions (practicing safe sex, avoiding
dirty needles) to prevent hepatitis



getting immunizations against hepatitis if a person is
in a high-risk group



receiving appropriate medical treatment quickly
when diagnosed with hepatitis B or hepatitis C



having blood drawn at regular intervals to rid the
body of excess iron from hemochromatosis
GALE ENCYCLOPEDIA OF MEDICINE



using medicines (chelating agents) to rid the body of
excess copper from Wilson’s disease
wearing protective clothing and following product
directions when using toxic chemicals at work, at
home, or in the garden

In 2001, research scientists identified the protein
segment and method in which excess tissue grows in
diseases like cirrhosis. With further study, the discovery might one day result in an oral or inhalable peptide
for those with cirrhosis.

ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
United Network for Organ Sharing. 1100 Boulders
Parkway, Suite 500, P.O. Box 13770, Richmond, VA
23225-8770. (804) 330-8500. <http://www.unos.org>.
OTHER

National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK). Cirrhosis of the Liver. April 200
[cited October 2002]. <http://www.niddk.nih.gov/
health/digest/pubs/cirrhosi/cirrhosi.htm>.

Resources

Maureen Haggerty
Rebecca J. Frey, PhD

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD. editors.
‘‘Cirrhosis.’’ Section 4, Chapter 41 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Alcoholism.’’ New York: Simon & Schuster, 2002.
PERIODICALS

Cha, C. H., L. Ruo, Y. Fong, et al. ‘‘Resection of
Hepatocellular Carcinoma in Patients Otherwise
Eligible for Transplantation.’’ Annals of Surgery 238
(September 2003): 315–321.
Foreman, M. G., D. M. Mannino, and M. Moss. ‘‘Cirrhosis
as a Risk Factor for Sepsis and Death: Analysis of the
National Hospital Discharge Survey.’’ Chest 124
(September 2003): 1016–1020.
Higuchi, H., and G. J. Gores. ‘‘Mechanisms of Liver Injury:
An Overview.’’ Current Molecular Medicine 3
(September 2003): 483–490.
Kamath, B. M., and D. A. Piccoli. ‘‘Heritable Disorders of
the Bile Ducts.’’ Gastroenterology Clinics of North
America 32 (September 2003): 857–875.
‘‘Management of Alcoholic Hepatitis.’’ Drug Therapy
Bulletin 41 (July 2003): 49–52.
Moretto, M., C. Kupski, C. C. Mottin, et al. ‘‘Hepatic
Steatosis in Patients Undergoing Bariatric Surgery
and Its Relationship to Body Mass Index and
Co-Morbidities.’’ Obesity Surgery 13 (August 2003):
622–624.
‘‘Peptides: Peptide Critical to Cirrhosis Development.’’ Drug
Discovery and Technology News 4, no. 11 (November
2001).
Phillips, M. G., V. R. Preedy, and R. D. Hughes.
‘‘Assessment of Prognosis in Alcoholic Liver Disease:
Can Serum Hyaluronate Replace Liver Biopsy?’’
European Journal of Gastroenterology and Hepatology
15 (September 2003): 941–944.
Ristig, M., H. Drechsler, J. Crippin, et al. ‘‘Management of
Chronic Hepatitis B in an HIV-Positive Patient with
3TC-Resistant Hepatitis B Virus.’’ AIDS Patient Care
and STDs 17 (September 2003): 439–442.
GALE ENCYCLOPEDIA OF MEDICINE

Cisapride see Antigastroesophageal reflux
drugs
CK test see Creatine kinase test
Clap see Gonorrhea
Clarithromycin see Erythromycins

I Cleft lip and palate
Definition
A cleft is a birth defect that occurs when the
tissues of the lip and/or palate of the fetus do not
fuse very early in pregnancy. A cleft lip, sometimes
referred to as a harelip, is an opening in the upper lip
that can extend into the base of the nostril. A cleft
palate is an opening in the roof of the mouth.

Description
Babies born with cleft lips will have an opening
involving the upper lip. The length of the opening
ranges from a small notch, to a cleft that extends into
the base of the nostril. Cleft lips may involve one or
both sides of the lip.
Babies born with cleft palates have openings in the
palate, which is the roof of the mouth. The size and
position of the opening varies. The cleft may be only in
the hard palate, the bony portion of the roof of the
mouth, opening into the floor of the nose. It may be
only in the soft palate, the soft portion of the roof of
the mouth. The cleft palate may involve both the hard
and soft palate and may occur on both sides of the
center of the palate.
901

Cleft lip and palate



Cleft lip and palate

Babies may have cleft lips with or without cleft
palates. Cleft palates may also occur without cleft lips.
The incidence of cleft lip and palate not associated
with a syndrome is one in 700 newborns. Native
Americans have an incidence of 3.6 in 1,000 newborns.
The incidence among Japanese newborns is 2.1 in
1,000. The incidence among whites is one in 1,000
newborns. African Americans have an incidence of
0.3 in 1,000 newborns.

Causes and symptoms
Cleft lips and palates not associated with a syndrome are caused by a combination of genetic and
environmental factors. Inheritance caused by such a
combination is called multifactorial. The embryo
inherits genes that increase the risk for cleft lip and/
or palate. When an embryo with such genes is exposed
to certain environmental factors the embryo develops
a cleft.
The risk of a baby being born with a cleft lip or
palate increases with the number of affected relatives
and the number of relatives that have more severe
clefts.
Environmental factors that increase the risk of
cleft lip and palate include cigarette and alcohol use
during pregnancy. Some drugs, such as phenytoin,
sodium valproate, and methotrexate, also increase
the incidence of clefting. The pregnant mother’s nutrition may affect the incidence of clefting as well.
Babies born with a cleft lip will be seen to have an
elongated opening in the upper lip. The size of this
opening may range from a small notch in the upper lip
to an opening that extends into the base of the nostril.
The cleft lip may be below the right or left nostril or
below both nostrils.
Babies born with a cleft palate will be seen to have
an opening into the roof of the mouth. The size and
position of the cleft varies and it may involve only the
hard palate, or only the soft palate and may occur on
both sides of the center of the palate.
In some cases the cleft palate will be covered with
the normal lining of the mouth and can only be felt by
the examiner.
Babies with cleft lips and palates have feeding
difficulties, which are more severe in babies with cleft
palates. The difficulty in feeding is due to the baby
being unable to achieve complete suction. In the case
of clefts of the hard palate, liquids enter the nose from
the mouth through the opening in the hard palate.
902

A cleft palate also affects a child’s speech, since
the palate is necessary for speech formation. The
child’s speech pattern may still be affected despite
surgical repair.
Ear infections are more common in babies born
with cleft palates. The infections occur because the
muscles of the palate do not open the Eustachian
tubes that drain the middle ear. This allows fluid to
collect and increases the risk of infection and hearing
loss.
Teeth may also erupt misaligned.

Diagnosis
Cleft lip and palate can be diagnosed before birth
by ultrasound. Magnetic resonance imaging (MRI)
offers more accuracy for detecting cleft lip and palate,
as it is a more detailed imaging method. It is particularly helpful in showing soft palate defects. In 2004,
researchers reported discovery of a gene test for isolated cleft lip and cleft palate to help predict if parents
who have one child with the isolated form of cleft lip or
palate were likely to have a second child with the same
defect. After birth, cleft lip and palate are diagnosed
by physical exam.

Treatment
If cleft lip and/or palate are diagnosed by ultrasound before birth, further testing may be required to
diagnose associated abnormalities if present. Referral
to a cleft team is essential. A cleft team consists of
specialists in the management of babies with clefts and
includes surgeons as well as nurses and speech therapists. Members of the team inform the parents of all
aspects of management. Feeding methods are also
discussed, since feeding is the first problem that must
be dealt with. It may be possible to breastfeed a baby
born with only a cleft lip, but babies born with cleft
palates usually have more problems with feeding and
frequently require special bottles and teats. A palatal
obturator is a device that fits into the roof of the
mouth, thus blocking the cleft opening and allowing
easier suckling.
Surgery to repair cleft lips is sometimes performed
after orthodontic treatment to narrow the gap in the
upper lip. The orthodontic treatment can involve
acrylic splints with or without screws or may involve
the use of adhesive tape placed across the gap in the
lip. The orthodontic treatment for cleft lip should be
started within the first three weeks of life and continue
until the cleft lip is repaired.
GALE ENCYCLOPEDIA OF MEDICINE

Babies born with clefts usually require orthodontic treatment between 13 and 18 years of age. They also
require speech therapy.

Prognosis
Babies born with cleft lip and palate have a good
prognosis, and approximately 80% will develop normal speech. There is no known means of preventing
clefting. Good prenatal care is essential and avoiding
harmful substances appear to reduce the risk.
Resources
PERIODICALS

This infant has a unilateral cleft lip and palate. (Custom
Medical Stock Photo. Reproduced by permission.)

The timing of surgical cleft lip repair depends on
the judgment of the surgeon who will perform the
operation. The procedure is usually performed
between one and three months of age. The goals of
the operation are to close the gap in the upper lip,
place scars in the natural skin curves and to repair
muscle so that the lip appears normal during movement. The closure is done in the three layers (skin,
muscle, and mucosa) that line the inside of the lip. At
the time of the procedure, if the nose is shaped abnormally due to the cleft lip, it is also corrected.
Sometimes further surgery may be needed on the lip
and/or nose to refine the result.
The goals of the surgeon repairing a cleft palate
are normal speech, normal facial growth, and hearing
for the affected infant. The repair of the cleft palate is
usually performed between three and 18 months of
age. The timing may extend beyond this and varies
with the type of cleft palate and center where the
procedure is being performed. Depending of the type
of cleft palate, more than one operation may be
needed to close the cleft and improve speech.
Nonsurgical treatment of a cleft palate is available
for patients who are at high risk for surgery and consists of a prosthetic appliance worn to block the opening in the palate.
Babies born with cleft palates are vulnerable to ear
infections. Their Eustachian tubes do not effectively
drain fluid from the middle ear so fluid accumulates
GALE ENCYCLOPEDIA OF MEDICINE

Bender, Patricia L. ‘‘Genetics of Cleft Lip and Palate.’’
Journal of Pediatric Nursing 15 (August 2000): 242–249.
Christensen, Karr. ‘‘The 20th Century Danish Facial Cleft
Population—Epidemiological and Genetic—
Epidemiolical Studies.’’ Cleft Palate—Craniofacial
Journal 36 (March 1999): 96-104.
Chung, Kevin C. ‘‘Maternal Cigarette Smoking during
Pregnancy and the Risk of Having a Child with Cleft
Lip/Palate.’’ Plastic and Reconstructive Surgery 105
(February 2000): 458–491.
Cockell, Anna. ‘‘Prenatal Diagnosis and Management of
Orofacial Clefts.’’ Prenatal Diagnosis 20 (February
2000): 149–151.
‘‘MRI More Accurate for Detecting Prenatal Cleft Lip and
Palate than Sonography.’’ Medical Devices & Surgical
Technology Week July 25, 2004: 160.
‘‘Researchers Report New Gene Test for Isolated Cleft Lip
and Palate.’’ Science Letter September 28, 2004: 518.
Rohrich, Rod J. ‘‘Optimal Timing of Cleft Palate
Closure.’’ Plastic and Reconstructive Surgery 106
(August): 413–421.
ORGANIZATIONS

Cleft Palate Foundation. (800) 24-CLEFT. <http://
www.cleftline.org>.

Farris Farid Gulli, M.D.
Teresa G. Odle

Cleft palate see Cleft lip and palate

I Clenched fist injury
Definition
A clenched fist injury (CFI) is a bite wound on the
hand, caused when a person’s closed fist strikes the
903

Clenched fist injury

and infection sets in. This may lead to hearing loss.
These children require drainage tubes to be inserted to
prevent fluid accumulation.

Clenched fist injury

teeth of another person, usually in the course of a
fight. CFIs are sometimes referred to as closed fist
injuries or fight bites.

happened. The treating physician must maintain a
high level of suspicion and often ask directly.

Treatment
Description
Clenched fist injuries are most common over the
metacarpo phalangeal joint. Their appearance is
deceptive because they do not bleed heavily and the
underlying injury is hidden by soft tissue when the
patient opens his hand and straightens the injured
finger. CFIs can, however, have serious consequences,
including infection, cellulitis, inflammation of the
bone or bone marrow (osteomyelitis), septic arthritis,
and inflammation of the sheaths covering the tendons
of the hand (tenosynovitis). These may lead to permanent loss of function or amputation.
Most CFIs result in tissue injury due to the force
of impact, ragged-edged tears in the skin resulting
from contact with the teeth, and contamination of
the wound by the bacteria in human saliva. As the
patient opens his hand, the skin of the finger is pulled
backward over the deeper part of the wound, thus
sealing bacteria within the injured tissue. This sealing
of the wound by normal motions of the finger is the
reason why clenched fist injuries have the highest rate
of infection of any human bite. The rate of infection of
clenched-fist injuries varies from 15–50%.

Causes and symptoms
The causes of CFIs include fighting and other
forms of aggressive behavior, often combined with
drug or alcohol consumption.
The symptoms of clenched-fist injury include pain
in the affected part of the hand and some stiffness of
the injured finger with limitation of movement. If the
patient has delayed getting medical treatment, there
may be evidence of infection, including swelling, redness, and suppuration (a discharge of pus). The skin
around the wound will be warm to the touch and fever
may be present.

Diagnosis
Diagnosis of clenched fist injuries is usually made
on the basis of the location of the injury and x-ray
findings. The most common finding in CFI x rays is
soft tissue swelling, but the x rays may also reveal air
pockets in deep tissues or the joint spaces, fragments
of teeth, fracture lines in the bones, or small loose bone
chips. Diagnosis is often complicated by the fact that
the patient will be reluctant to admit how the injury
904

Treatment of clenched fist injuries is complicated
by several factors. One factor is the anatomical structure of the human hand, which contains many small
closed spaces that make it easy for infection to spread
and persist. Another is the number of disease-causing
bacteria transmitted by human bites; at least 42 different species have been identified. In addition, CFIs
typically do not receive immediate treatment because
the patient is concerned about legal consequences. The
longer the delay, the higher the chances of infection
and permanent damage to the hand. Patients who wait
longer than 24 hours to seek treatment or have signs of
infection or damage to the tendon, joint capsule, or
bones are usually referred immediately to a doctor
who specializes in hand surgery.
The first step in treatment of clenched fist injury is
irrigation, a procedure by which the wound is flushed
with a stream of water under high pressure or with an
antiseptic solution. Incision and drainage of the
wound (I&D) may be required as well as debridement,
the surgical removal of dead tissue and foreign objects
from a wound. Careful examination of the depth of the
wound is essential to proper treatment. The surgeon
may need to enlarge the sides of the wound in order to
make an accurate evaluation. The patient will be asked
to move the affected joint through its full range of
motion so that the surgeon can determine whether
the tendon or joint capsule has been damaged.
Following these procedures, the surgeon will pack
the wound and put the hand in a splint. Bite wounds
are never sutured (sewn shut) because of the possibility
of enclosing bacteria inside the injury. After 24 hours,
the packing will be removed and the hand reexamined
for signs of infection.
If the wound has become infected, the patient is
usually hospitalized and given parenteral (injectable)
antibiotics. The wound is irrigated and examined to
determine the extent of the injury. Cultures are taken
for both aerobic (requiring air or oxygen to live) and
anaerobic (not requiring air or oxygen) species of
bacteria. The cultures should be taken from areas
deep in the wound rather than from the surface for
greater accuracy. Tetanus toxoid should be given if
the patient has not been immunized within the
last 10 years. The patient should also receive treatment and follow-up for the rare possibility of
HIV and hepatitis transmission. Although no welldocumented cases of HIV transmission by human
GALE ENCYCLOPEDIA OF MEDICINE

Antibiotic—A chemical substance produced by a
microorganism which can inhibit the growth of or
kill other microorganisms.
Debridement—Surgical removal of damaged tissue and foreign objects from a wound.
I&D—Incision and drainage of a wound.
Irrigation—Cleansing a wound with large amounts
of water and/or an antiseptic solution.
Parenteral—Administered inside the body but outside the digestive tract.
Tetanus toxoid—Tetanus toxoid is a vaccine used
to prevent tetanus (also known as lockjaw).

punches at their opponent’s mouth. The next best
preventive measure is to get medical treatment at
once for a clenched-fist injury.
Resources
BOOKS

Jacobs, Richard A., MD. ‘‘Animal & Human Bite Wounds.’’
In ‘‘General Problems in Infectious Diseases.’’ Current
Medical Diagnosis & Treatment 2001, edited by
L. M. Tierney, Jr., MD, et al., 40th ed. New York:
Lange Medical Books/McGraw-Hill, 2001.
Taylor, Mark D., MD, and Samuel E. Wilson, MD.
‘‘Bacterial Diseases of the Skin.’’ In Conn’s Current
Therapy 2001, edited by Robert E. Rakel, MD and
Edward T. Bope, MD. Philadelphia: W. B. Saunders
Company, 2001.
PERIODICALS

‘‘Do All Human Bite Wounds Need Antibiotics?’’
Emergency Medicine Alert June 2004: 3.

bites exist as of 2001, the potential for transmission
by this route is still present.
Infected clenched fist injuries usually contain
several disease-causing bacteria, the most common
being Streptococcus pyogenes, Staphylococcus aureus,
Bacteroides sp., Peptostreptococcus sp., and Eikenella
corrodens. Broad-spectrum antibiotics are usually
given. Uninfected and relatively superficial CFIs
may be treated with oral penicillin plus dicloxacillin
or Augmentin. For infected CFIs, parenteral penicillin G is usually given together with nafcillin or cefuroxime. CFIs infected by drug-resistant strains of
S. aureus may require treatment with vancomycin.
While some human bite wounds do not require
routine use of antibiotics, a 2004 study confirmed
that puncture wounds, deeper lacerations and bites
to the hand all have high infection rates which may be
lowered by preventive use of antibiotics.

ORGANIZATIONS

Massachusetts College of Emergency Physicians (MACEP).
P. O. Box 296, Swansea, MA 02777. (508) 643-0117.
Fax: (508) 643-0141.

Rebecca J. Frey, PhD
Teresa G. Odle

Climacteric see Menopause
Clomiphene see Infertility drugs
Clonazepam see Benzodiazepines
Closed fracture reduction see Fracture repair
Clostridium difficile colitis see Antibioticassociated colitis
Clotrimazole see Antifungal drugs, topical
Clotting disorders see Coagulation disorders

Prognosis
The prognosis depends on the patient’s underlying state of health and compliance with treatment;
depth of the wound; the involvement of the joint capsule or tendon; and the length of time before the
wound is treated. The more superficial the wound
and the faster the treatment, the better the prognosis.

Prevention
The best way to prevent clenched fist injuries is to
avoid fist fights, intoxication, and association with
people who practice these forms of behavior. If
involved in a fist fight, people should avoid directing
GALE ENCYCLOPEDIA OF MEDICINE

I Club drugs
Definition
Club drugs is the generic term for psychoactive
drugs, usually illegal, that are used by participants of
the rave and dance club and recreational drug
subculture.

Description
The most commonly used club drugs are MDMA
(ecstasy), LSD, psilocybin mushrooms, rohypnol, GHB,
905

Club drugs

KEY TERMS

Club drugs

and methamphetamine. These substances are illegal and
strictly controlled. Each drug has different effects and
possible complications.
MDMA, or ecstasy (also XTC, X, or E) is a semisynthetic drug that was patented in 1914 by the Merck
Corporation. The drug was not used for six decades,
until interest in it gathered in the 1970s and 1980s,
stimulated in part by psychologists and therapists who
began experimenting with its possible uses in treating
some psychological conditions including anxiety,
depression, and post traumatic stress syndrome. Users
reported powerfully euphoric or ecstatic effects of the
substance, and use of the drug spread into the recreational drug subculture. Due to health concerns over use
of the drug, it was made a controlled substance in the
1980s, but manufacture and use of the drug has continued. Raves are events in which participants take the
substance and dance to rhythmic, stimulating music.
Some scientists have classified the drug as a hallucinogen, while some psychologists have termed the drug an
empathogen, meaning it increases a sense of empathy
for self and others when used in a controlled environment. MDMA is the most commonly used drug in the
rave and dance club subculture.
MDMA (3,4-methylenedioxymethamphetamine)
has stimulating effects in the body, and can create
changed perceptions of time, environment, and tactile
senses. It can cause an increase in body temperature,
heart rate, and blood pressure. In some cases it can
cause unpleasant feelings of anxiety and paranoia. It
works in the body by affecting the serotonin system in
the brain. Serotonin is the neurotransmitter responsible for feelings of well-being and elevated mood.
MDMA causes the brain to be flooded with the neurotransmitter, which creates a feeling of euphoria in
the user. After the effects of the drug wear off, a
temporary decrease in serotonin levels is caused in
the brain, and users may report feelings of mild
depression for days or weeks after ingestion.
MDMA is generally taken in doses of 125 milligrams, although effects are observable by ingestion of
as little as 60 milligrams. It is generally swallowed in
tablets or capsules. Effects begin about one hour after
ingestion, reaching a peak after three or four hours,
and fading after about six hours. Users commonly
ingest a second dose to prolong the effects.
Dangers associated with the drug include
increased body temperature, that may be complicated
by hot environments and physical activities such
as dancing or immersion in hot tubs or saunas.
Dehydration is a common occurrence with the drug.
It can also cause increased heart rate and blood
906

pressure. There is debate in the scientific community
about the effects of the substance on the brain, due to a
lack of human studies. Some animal studies have
shown that MDMA can negatively affect the serotonin system in the brain and damage neurons. Studies
have implied that long-term MDMA users may have
decreased memory function. Other problems associated with the substance arise when the chemical is
adulterated by more dangerous substances such as
methamphetamines and toxic compounds, and mixing
MDMA with other intoxicants including alcohol and
cocaine. MDMA is dangerous for people with heart
disease or high blood pressure, and may increase or
aggravate symptoms in people with psychological
disorders.
LSD (lysergic acid) and psilocybin mushrooms
are psychedelic or hallucinogenic substances. Effects
of these drugs range from euphoria to intense hallucinations and distorted or enhanced perceptions.
Dangers associated with these substances include temporary loss of physical and emotional control and
psychological distress.
Rohypnol (flunitrazepam) is a powerful sedative
that has been termed a ‘‘date rape’’ drug. It can cause
‘‘anterograde amnesia’’ meaning that those taking the
substance may lose memory of events occurring under
its effects. It may be fatal when combined with alcohol
and other depressants.
GHB (gamma hydroxybutyrate) is a substance
with euphoric, depressant, and anabolic (body building) effects in the body. Overdoses can cause seizures
and comas, and the substance can be dangerously
combined with alcohol and other sedatives. It has
also been termed a date rape drug, due to its powerful
sedative effects when combined with alcohol.
Methamphetamine is a dangerously addictive stimulant, known as ‘‘ice’’ and ‘‘crystal’’ among users. It
is taken orally, intranasally (through the nose) and
intravenously. Effects in the body include an intense
rush of euphoric feelings and stimulating effects, followed by an addictive need for more of the substance.
It causes elevated heart rate and increased blood pressure. Research using animals has shown the substance
can cause brain and nervous system damage. It has
also been implicated in causing damage to the blood
vessels in the brain, respiratory problems, irregular
heartbeat, anorexia, and in extreme cases may cause
heart failure and death. Emotional problems associated with use of methamphetamine include addiction, paranoia, anxiety, and insomnia. The use of
methamphetamine has been growing in the United
States throughout the 2000s.
GALE ENCYCLOPEDIA OF MEDICINE

Clubfoot

I Clubfoot

KEY TERMS
Anorexia—Eating disorder associated with extreme
fluctuations and loss in body weight.
Hallucinogen—Substance that causes distorted
perceptions and hallucinations.
Neurotransmitter—Chemical in the brain that
assists brain function.
Psychoactive—Substance that effects emotional
and psychological perception in the brain.

Diagnosis
Substance abuse is defined by the Diagnostic and
Statistical Manual IV as occurring when: users take a
substance in larger amounts or over longer time periods
than intended; a persistent and unsuccessful desire to
cease usage; spending large quantities of time procuring
the substance; reduction in other social activities; continued use of a substance despite physical or emotional
problems caused by the substance; increased tolerance
of the substance; withdrawal symptoms or increased
use of a substance to avoid withdrawal symptoms.

Treatment
Treatment for problems associated with the use and
abuse of club drugs include psychiatric, psychological,
and substance abuse counseling, as well as emergency
medical treatment for overdoses and complications.
Resources
BOOKS

Eisner, Bruce. Ecstacy: The MDMA Story. Ronin Books, 1993.
Holland, Julie, M.D. Ecstacy: The Complete Guide: A
Comprensive Look at the Risks and Benefits of MDMA.
Park Street Press, 2001.
Knowles, Cynthia. Up All Night: A Closer Look at the Club
Drugs and Rave Culture. Red House Books, 2001.
Stafford, Peter. Psychedelics Encyclopedia. Ronin Books, 1992.
ORGANIZATIONS

DanceSafe. 536 45th Ave., Oakland, CA 94609. <http://
www.dancesafe.org>.
Multidisciplinary Association for Psychedelic Studies. 2105
Robinson Ave., Sarasota, FL 34232. (941) 924-6277.
<http://www.maps.org>.
National Institute on Drug Abuse. 6001 Executive Blvd.,
Room 5213, Bethesda, MD 20892-9561. <http://
www.drugabuse.gov>.

Douglas Dupler
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Clubfoot is a condition in which one or both feet are
twisted into an abnormal position at birth. The condition is also known as talipes or talipes equinovarus.

Description
True clubfoot is characterized by abnormal bone
formation in the foot. There are four variations of
clubfoot, including talipes varus, talipes valgus, talipes
equines, and talipes calcaneus. In talipes varus, the
most common form of clubfoot, the foot generally
turns inward so that the leg and foot look somewhat
like the letter J. In talipes valgus, the foot rotates outward like the letter L. In talipes equinus, the foot
points downward, similar to that of a toe dancer. In
talipes calcaneus, the foot points upward, with the heel
pointing down.
Clubfoot can affect one foot or both. Sometimes
an infant’s feet appear abnormal at birth because of
the intrauterine position of the fetus birth. If there is
no anatomic abnormality of the bone, this is not true
clubfoot, and the problem can usually be corrected
by applying special braces or casts to straighten the
foot.
The ratio of males to females with clubfoot is 2.5
to 1. The incidence of clubfoot varies only slightly. In
the United States, the incidence is approximately 1 in
every 1,000 live births. A 1980 Danish study reported
an overall incidence of 1.20 in every 1,000 children;
by 1994, that number had doubled to 2.41 in every
1,000 live births. No reason was offered for the
increase.

Causes and symptoms
Experts do not agree on the precise cause of clubfoot. The exact genetic mechanism of inheritance has
been extensively investigated using family studies and
other epidemiological methods. No definitive conclusions have been reached as of the early 2000s,
although a Mendelian pattern of inheritance is suspected. This may be due to the interaction of several
different inheritance patterns, different patterns of
development appearing as the same condition, or a
complex interaction between genetic and environmental factors. The MSX1 gene has been associated
with clubfoot in animal studies. As of the early 2000s,
however, these findings have not been replicated in
humans.
907

Clubfoot

A family history of clubfoot has been reported in
24.4% of families in a single study. These findings
suggest the potential role of one or more genes being
responsible for clubfoot.
Several environmental causes have been proposed
for clubfoot. Obstetricians feel that intrauterine crowding causes clubfoot. This theory is supported by a significantly higher incidence of clubfoot among twins
compared to singleton births. Intrauterine exposure to
the drug misoprostol has been linked with clubfoot.
Misoprostol is commonly used when trying, usually
unsuccessfully, to induce abortion in Brazil and in
other countries in South and Central America.
Researchers in Norway have reported that males who
are in the printing trades have significantly more offspring with clubfoot than men in other occupations.
For unknown reasons, amniocentesis, a prenatal test,
has also been associated with clubfoot. One international study published in 2004 reported that amniocentesis done at 13 weeks of gestation was associated
with a fourfold increase in the risk of clubfoot. The
infants of mothers who smoke during pregnancy have
a greater chance of being born with clubfoot than are
offspring of women who do not smoke.
True clubfoot is usually obvious at birth. The four
most common varieties have been described. A clubfoot has a typical appearance of pointing downward
and being twisted inwards. Since the condition starts in
the first trimester of pregnancy, the abnormality is quite
well established at birth, and the foot is often very rigid.
Uncorrected clubfoot in an adult causes only part of the
foot, usually the outer edge, or the heel or the toes, to
touch the ground. For a person with clubfoot, walking
becomes difficult or impossible.

Diagnosis
True clubfoot is usually recognizable and obvious
on physical examination. A routine x ray of the foot that
shows the bones to be malformed or misaligned supplies
a confirmed diagnosis of clubfoot. Ultrasonography is
not always useful in diagnosing the presence of clubfoot
prior to the birth of a child; however, ultrasound is
increasingly used in the early 2000s to evaluate the
severity of clubfoot after birth and monitor its response
to treatment.

Treatment
Most orthopedic surgeons agree that the initial
treatment of congenital (present at birth) clubfoot
should be nonoperative. Nonsurgical treatment should
begin in the first days of life to take advantage of the
908

Person suffering from clubfoot. About one of every 400 newborns has some form of this birth defect. (Photo Researchers,
Inc. Reproduced by permission.)

favorable fibroelastic properties of the foot’s connective tissues, those forming the ligaments, joint capsules,
and tendons. In a common treatment, a series of casts is
applied over a period of months to reposition the foot
into normal alignment. In mild cases, splinting and
wearing braces at night may correct the abnormality.
Another treatment for clubfoot is the Ilizarov
frame, named for the Russian physician who developed it in 1951. The Ilizarov frame has been used in the
United States and Canada since 1981. It consists of
two metal rings that encircle the leg to be corrected,
wires that attach the rings to the bone, and metal rods
between the rings that can be extended like a telescope.
The frame must be applied by an orthopedic surgeon.
After a week, the surgeon begins to lengthen the rods,
usually at the rate of 1 mm per day. The frame must be
kept in place for several months. Although the Ilizarov
frame is somewhat cumbersome, it has been reported
GALE ENCYCLOPEDIA OF MEDICINE

Enterovirus—Any of a group of viruses that primarily affect the gastrointestinal tract.
Ilizarov frame—A device invented by a Russian
physician for correcting deformities of the legs
and feet, consisting of rings to be attached to the
bone and rods extending between the rings that
stretch the affected limb.
Intrauterine—Situated or occuring in the uterus.
Orthopedist—A doctor specializing in treatment of
the skeletal system and its associated muscles and
joints.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Musculoskeletal Abnormalities.’’ Section 19, Chapter
261 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Hall, Judith G. ‘‘Chromosomal Clinical Abnormalilties.’’ In
Nelson Textbook of Pediatrics, edited by Richard E.
Behrman, et al., 16th ed. Philadelphia: Saunders, 2000,
325–34.
Van Allen, Margot I., and Judith G. Hall. ‘‘Congenital
Anomalies.’’ In Cecil Textbook of Medicine, edited by
Lee Goldman, et al., 21st ed. Philadelphia: Saunders,
2000, 150–52.
PERIODICALS

as giving satisfactory results in straightening clubfeet,
particularly those untreated in infancy.
When clubfoot is severe enough to require surgery,
the condition is usually not completely correctable,
although significant improvement is possible. In the
most severe cases, surgery may be required, especially
when the Achilles tendon, which joins the muscles in the
calf to the bone of the heel, needs to be lengthened.
Because an early operation induces fibrosis, a scarring
and stiffness of the tissue, surgery should be delayed
until an affected child is at least three months old.
Much of a clubfoot abnormality can be corrected
by the use of manipulation and casting during the first
three months of life. Proper manipulative techniques
must be followed by applications of appropriately
molded plaster casts to provide effective and safe correction of most varieties of clubfoot. Long-term care
by an orthopedist is required after initial treatment to
ensure that the correction of the abnormality is maintained. Exercises, corrective shoes, or nighttime splints
may be needed until the child stops growing.

Prognosis
With prompt, expert treatment, clubfoot is
usually correctable. One group of French researchers
found that 77% of the children they followed over a
period of 11 to 18 years had good results from nonsurgical methods of treatment combined with physical
therapy. Most individuals are able to wear regular
shoes and lead active lives. If clubfoot is not appropriately treated, however, the abnormality may
become fixed. This fixation affects the growth of the
child’s leg and foot, and some degree of permanent
disability usually results.
GALE ENCYCLOPEDIA OF MEDICINE

El Barbary H., H. Abdel Ghani, and M. Hegazy.
‘‘Correction of Relapsed or Neglected Clubfoot Using a
Simple Ilizarov Frame.’’ International Orthopedics 28
(June 2004): 183–186.
Gigante, C., E. Talente, and S. Turra. ‘‘Sonographic
Assessment of Clubfoot.’’ Journal of Clinical
Ultrasound 32 (June 2004): 235–242.
Philip, J., R. K. Silver, R. D. Wilson, et al. ‘‘Late FirstTrimester Invasive Prenatal Diagnosis: Results of an
International Randomized Trial.’’ Obstetrics and
Gynecology 103 (June 2004): 1164–1173.
Souchet, P., H. Bensahel, C. Themar-Noel, et al.
‘‘Functional Treatment of Clubfoot: A New Series of
350 Idiopathic Clubfeet with Long-Term Follow-Up.’’
Journal of Pediatric Orthopaedics, Part B 13 (May
2004): 189–196.
ORGANIZATIONS

March of Dimes/Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (888)
663-4637. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Easter Seal Society. 230 W. Monroe St., Suite 1800,
Chicago, IL 60606-4802. (312) 726-6200 or (800)
221-6827. <http://www.easter-seals.org>.
National Organization for Rare Disorders (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT 068131968. (203) 744-0100 or (800) 999-6673. Fax: (203)
798-2291. <http://www.rarediseases.org>.
OTHER

Children’s and Women’s Health Centre of British Columbia.
The Ilizarov Apparatus. <http://www.cw.bc.ca/
orthopaedics/Ilizarov.asp>.
‘‘Clubfoot.’’ National Library of Medicine. <http://
www.nlm.nih.gov/medlineplus/ency/article/
001228.htm>.
Clubfoot.net. <http://www.clubfoot.net/treatment.php3>.

L. Fleming Fallon, Jr., MD, DrPH
Rebecca J. Frey, PhD
909

Clubfoot

Resources

KEY TERMS

Cluster headache

I Cluster headache

Areas of pain

Definition
Cluster headaches are characterized by an intense
one-sided pain centered by the eye or temple. The pain
lasts for one to two hours on average and may recur
several times in a day.

Nerves

Description
Cluster headaches have been known as histamine
headaches, red migraines, and Horton’s disease,
among others. The constant factor is the pain, which
transcends by far the distress of the more common
tension-type headache or even that of a migraine
headache.
Cluster headaches afflict less than 0.5% of the
population and predominantly affect men; approximately 80% of sufferers are male. Onset typically
occurs in the late 20s, but there is no absolute age
restriction. Approximately 80% of cluster headaches
are classified as episodic; the remaining 20% are
considered chronic. Both display the same symptoms. However, episodic cluster headaches occur
during oneto five-month periods followed by six to
24-month attack-free, or remission, periods. There
is no such reprieve for chronic cluster headache
sufferers.

Causes and symptoms
Biochemical, hormonal, and vascular changes
induce cluster headaches, but why these changes occur
remains unclear. Episodic cluster headaches seem to be
linked to changes in day length, possibly signaling a
connection to the so-called biological clock. Alcohol,
tobacco, histamine, or stress can trigger cluster headaches. Decreased blood oxygen levels (hypoxemia)
can also act as a trigger, particularly during the night
when an individual is sleeping. Interestingly, the triggers do not cause cluster headaches during remission
periods.
The primary cluster headache symptom is excruciating one-sided head pain centered behind an eye or
near the temple. This pain may radiate outward from
the initial focus and encompass the mouth and teeth.
For this reason, some cluster headache sufferers may
mistakenly attribute their pain to a dental problem.
Secondary symptoms, occurring on the same side as
the pain, include eye tearing, nasal congestion followed by a runny nose, pupil contraction, and facial
drooping or flushing.
910

Cluster Headache
The primary cluster headache symptom is excruciating onesided head pain located behind an eye or near the temple.
Secondary symptoms include eye tearing, nasal congestion,
and a runny nose. (Illustration by Electronic Illustrators Group.)

Diagnosis
Cluster headache symptoms guide the diagnosis.
A medical examination includes recording headache
details, such as frequency and duration, when it
occurs, pain intensity and location, possible triggers,
and any prior symptoms. This history allows other
potential problems to be discounted.

Treatment
Treatment for cluster headaches is composed of
induction, maintenance, and symptomatic therapies.
The first two therapies are prophylactic treatments,
geared toward preventing headaches. Symptomatic
therapy is meant to stop or shorten a headache.
Induction and maintenance therapies begin together.
Induction therapy is intended to break the headache
cycle with drugs such as corticosteroids (for example,
prednisone) or dihydroergotamine. These drugs are
not meant for long-term therapy, but rather as a
jump-start for maintenance therapy. Maintenance
therapy drugs include verapamil, lithium carbonate,
ergotamine, and methysergide. These drugs have longterm effectiveness, but must be taken for at least a
week before a response is observed. With long-term
GALE ENCYCLOPEDIA OF MEDICINE

Biological clock—A synonym for the body’s circadian rhythm, the natural biological variations that
occur over the course of a day.
Migraine headache—An intense throbbing pain that
occurs on one or both sides of the head. The headache is usually accompanied by other symptoms,
such as nausea, vomiting, and aversion to light.
Prophylactic—Referring to treatment that prevents
symptoms from occurring.
Tension-type headache—A dull pain that seems to
exert pressure on the head; the most common form
of headache.

treatment, methysergide must be stopped for one
month each year to avoid dangerous side effects (formation of fibrous tissue inside the abdominal artery,
lungs, and heart valves).
Despite prophylactic treatment, headaches may
still occur. Symptomatic therapy includes oxygen
inhalation, sumatriptan injection, and application of
local anesthetics inside the nose. Surgery is a last resort
for chronic cluster headaches that fail to respond to
therapy.

chamomile (Matricaria recutita), rosemary (Rosemarinus
officinalis), and skullcap (Scutellaria baicalensis).

Prognosis
In general, drug therapy offers effective treatment.

Prevention
Avoiding triggers, adhering to medical treatment,
and controlling stress can help ward off some cluster
headaches.
Resources
ORGANIZATIONS

American Council for Headache Education (ACHE). 19
Mantua Road, Mt. Royal, NJ 08061. (800) 255-2243.
<http://www.achenet.org>.
National Headache Foundation. 428 W. St. James Place,
Chicago, IL 60614. (800) 843-2256. <http://
www.headaches.org>.

Julia Barrett

CMV see Cytomegalovirus infection
CNS depressants see Central nervous system
depressants
CNS stimulants see Central nervous system
stimulants

Alternative treatment
Since some cluster headaches are triggered by
stress, stress reduction techniques, such as yoga, meditation, and regular exercise, may be effective. Some
cluster headaches may be an allergic response triggered by food or environmental substances, therefore
identifying and removing the allergen(s) may be key to
resolution of the problem. Histamine is another suspected trigger of cluster headaches, and this response
may be controlled with vitamin C and the bioflavonoids quercetin and bromelain (pineapple enzyme).
Supplementation with essential fatty acids (EFA) will
help decrease any inflammatory response.
Physical medicine therapies such as adjustments
of the spine, craniosacral treatment, and massage at
the temporomandibular joint (TMJ) can clear
blockages, as can traditional Chinese medical therapies including acupuncture. Homeopathic treatment
can also be beneficial. Nervous system relaxant
herbs, used singly or in combination, can allow the
central nervous system to relax as well as assist in
peripheral nerve response. A few herbs to consider
for relaxation are valerian (Valeriana officinalis),
GALE ENCYCLOPEDIA OF MEDICINE

I Coagulation disorders
Definition
Coagulation disorders deal with disruption of the
body’s ability to control blood clotting. The most
commonly known coagulation disorder is hemophilia,
a condition in which patients bleed for long periods of
time before clotting. There are other coagulation disorders with a variety of causes.

Description
Coagulation, or clotting, occurs as a complex process involving several components of the blood.
Plasma, the fluid component of the blood, carries a
number of proteins and coagulation factors that regulate bleeding. Platelets, small colorless fragments in
the blood, initiate contraction of damaged blood vessels so that less blood is lost. They also help plug
damaged blood vessels and work with plasma to
911

Coagulation disorders

KEY TERMS

Coagulation disorders

accelerate blood clotting. A disorder affecting platelet
production or one of the many steps in the entire
process can disrupt clotting.
Coagulation disorders arise from different causes
and produce different complications. Some common
coagulation disorders are:


Hemophilia, or hemophilia A (Factor VIII deficiency), an inherited coagulation disorder, affects
about 20,000 Americans. This genetic disorder is
carried by females but most often affects males.



Christmas disease, also known as hemophilia B or
Factor IX deficiency, is less common than hemophilia A with similar in symptoms.



Disseminated intravascular coagulation disorder,
also known as consumption coagulopathy, occurs
as a result of other diseases and conditions. This
disease accelerates clotting, which can actually
cause hemorrhage.



Thrombocytopenia is the most common cause of coagulation disorder. It is characterized by a lack of
circulating platelets in the blood. This disease also
includes idiopathic thrombocytopenia.



Von Willebrand’s disease is a hereditary disorder
with prolonged bleeding time due to a clotting factor
deficiency and impaired platelet function. It is the
most common hereditary coagulation disorder.



Hypoprothrombinemia is a congenital deficiency of
clotting factors that can lead to hemorrhage.



Other coagulation disorders include Factor XI deficiency, also known as hemophilia C, and Factor VII
deficiency. Hemophilia C afflicts one in 100,000 people and is the second most common bleeding disorder
among women. Factor VII is also called serum prothrombin conversion accelerator (SPCA) deficiency.
One in 500,000 people may be afflicted with this
disorder that is often diagnosed in newborns because
of bleeding into the brain as a result of traumatic
delivery.

Causes and symptoms
Some coagulation disorders present symptoms
such as severe bruising. Others will show no apparent
symptoms, but carry the threat of severe internal
bleeding.
Hemophilia
Because of its hereditary nature, hemophilia A
may be suspected before symptoms occur. Some
signs of hemophilia A are numerous large, deep bruises
and pain and swelling of joints caused by internal
912

bleeding. Patients with hemophilia do not bleed faster,
just longer. A person with mild hemophilia may first
discover the disorder with prolonged bleeding following a surgical procedure. If there is bleeding into the
neck, head, or digestive tract, or bleeding from an
injury, emergency measures may be required.
Mild and severe hemophilia A are inherited
through a complex genetic system that passes a recessive gene on the female chromosome. Women usually
do not show signs of hemophilia but are carriers of the
disease. Each male child of the carrier has a 50%
chance of having hemophilia, and each female child
has a 50% chance of passing the gene on.
Christmas disease
Christmas disease, or hemophilia B, is also hereditary but less common than hemophilia A. The
severity of Christmas disease varies from mild to
severe, although mild cases are more common. The
severity depends on the degree of deficiency of the
Factor IX (clotting factor). Hemophilia B symptoms
are similar to those of hemophilia A, including numerous, large and deep bruises and prolonged bleeding.
The more dangerous symptoms are those that represent possible internal bleeding, such as swelling of
joints, or bleeding into internal organs upon trauma.
Hemophilia most often occurs in families with a
known history of the disease, but occasionally, new
cases will occur in families with no apparent history.
Disseminated intravascular coagulation
The name of this disorder arises from the fact that
malfunction of clotting factors cause platelets to clot
in small blood vessels throughout the body. This
action leads to a lack of clotting factors and platelets
at a site of injury that requires clotting. Patients with
disseminated intravascular coagulation (DIC) will
bleed abnormally even though there is no history of
coagulation abnormality. Symptoms may include
minute spots of hemorrhage on the skin, and purple
patches or hematomas caused by bleeding in the skin.
A patient may bleed from surgery or intravenous
injection (IV) sites. Related symptoms include vomiting, seizures, coma, shortness of breath, shock, severe
pain in the back, muscles, abdomen, or chest.
DIC is not a hereditary disorder or a common
one. It is most commonly caused by complications
during pregnancy or delivery, overwhelming infections, acute leukemia, metastatic cancer, extensive
burns and trauma, and even snakebites. There are a
number of other causes of DIC, and it is not commonly understood why or how these various disorders
GALE ENCYCLOPEDIA OF MEDICINE

Thrombocytopenia
Thrombocytopenia may be acquired or congenital. It represents a defective or decreased production of
platelets. Symptoms include sudden onset of small
spots of hemorrhage on the skin, or bleeding into
mucous membranes (such as nosebleeds). The disorder may also be evident as blood in vomit or stools,
bleeding during surgery, or heavy menstrual flow in
women. Some patients show none of these symptoms,
but complain of fatigue and general weakness. There
are several causes of thrombocytopenia, which is more
commonly acquired as a result of another disorder.
Common underlying disorders include leukemia, drug
toxicity, or aplastic anemia, all of which lead to decreased or defective production of platelets in the bone
marrow. Other diseases may destroy platelets outside
the marrow. These include severe infection, disseminated intravascular coagulation, and cirrhosis of the
liver. The idiopathic form most commonly occurs in
children, and is most likely the result of production of
antibodies that cause destruction of platelets in the
spleen and to a lesser extent the liver.
Von Willebrand’s disease is caused by a defect in
the Von Willebrand clotting factor, often accompanied
by a deficiency of Factor VIII as well. It is a hereditary
disorder that affects both males and females. In rare
cases, it may be acquired. Symptoms include easy bruising, bleeding in small cuts that stops and starts, abnormal bleeding after surgery, and abnormally heavy
menstrual bleeding. Nosebleeds and blood in the stool
with a black, tarlike appearance are also signs of Von
Willebrand’s disease.

liver. Prothrombin, under the right conditions, is converted to thrombin, which activates fibrin and begins
the process of coagulation. Some patients may show no
symptoms, and others will suffer severe hemorrhaging.
Patients may experience easy bruising, profuse nosebleeds, postpartum hemorrhage, excessively prolonged or
heavy menstrual bleeding, and postsurgical hemorrhage. Hypoprothrombinemia may also be acquired
rather than inherited, and usually results from a
Vitamin K deficiency caused by liver diseases, newborn
hemorrhagic disease, or a number of other factors.
Other coagulation disorders
Factor XI deficiency, or hemophilia C, occurs
more frequently among certain ethnic groups, with
an incidence of about one in 10,000 among
Ashkenazi Jews. Nearly 50% of patients with this
disorder experience no symptoms, but others may
notice blood in their urine, nosebleeds, or bruising.
Although joint bleeding seldom occurs, some factor
XI patients will experience bleeding long after an
injury occurs. Some women will experience prolonged
bleeding after childbirth. Patients with factor VII deficiency vary greatly in their bleeding severity. Women
may experience heavy menstrual bleeding, bleeding
from the gums or nose, bleeding deep within the
skin, and episodes of bleeding into the stomach, intestine, and urinary tract. Factor VII patients may also
suffer bleeding into joints.

Diagnosis
Several blood tests can be used to detect various
coagulation disorders. There are hundreds of different
tests a doctor can order to look for indications of
specific diseases. In addition to blood tests, physicians
will complete a medical history and physical examination. In the case of acquired coagulation disorders,
information such as prior or current diseases and
medications will be important in determining the
cause of the blood disorder.


Hemohilia A will be diagnosed with laboratory tests
detecting presence of clotting factor VIII, factor IX,
and others, as well as the presence or absence of
clotting factor inhibitors.



Christmas disease will be checked against normal
bleeding and clotting time, as well as for abnormal
serum reagents in factor IX deficiency. Other tests of
prothrombin time and thromboplastic generation
may also be ordered.



There is no one test or group of tests that can always
make (or exclude) a diagnosis of DIC. DIC can be

Hypoprothrombinemia
This disorder is a deficiency in prothrombin, or
Factor II, a glycoprotein formed and stored in the
GALE ENCYCLOPEDIA OF MEDICINE

913

Coagulation disorders

can lead to the coagulation problem. What the underlying causes of DIC have in common is some factor
that affects proteins, platelets, or other clotting factors
and processes. For example, uterine tissue can enter
the mother’s circulation during prolonged labor,
introducing foreign proteins into the blood, or the
venom of some exotic snakes can activate one of the
clotting factors. Severe head trauma can expose blood
to brain tissue. No matter the cause of DIC, the results
are a malfunction of thrombin (an enzyme) and prothrombin (a glycoprotein), which activate the fibrinolytic system, releasing clotting factors in the blood.
DIC can alternate from hemorrhage to thrombosis,
and both can exist, which further complicates diagnosis and treatment.

Coagulation disorders

diagnosed through a number of laboratory tests
which measure concentration of platelets and fibrinogen in the blood with normal counts and prolonged prothrombin time. Other supportive data
include diminished levels of factors V, fibrinogen,
and VIII, decreased hemoglobin, and others. Since
many of the test results also indicate other disorders,
the physician may have to put together several results
to reach a diagnosis of DIC. Serial tests may also be
recommended, because a single examine at one
moment in time may not reveal the process that is
occurring.


Tests for thrombocytopenia include coagulation tests
revealing a decreased platelet count, prolonged bleeding time, and other measurements. If these tests indicate that platelet destruction is causing the disorder,
the physician may order bone marrow examination.



Von Willebrand’s disease will be diagnosed with the
assistance of laboratory tests which show prolonged
bleeding time, absent or reduced levels of factor VIII,
normal platelet count, and others.



Hypothrombinemia is diagnosed with history information and the use of tests that measure vitamin K
deficiency, deficiency of prothrombin, and clotting
factors V, VII, IX, and X.



Factor XI deficiency is diagnosed most often after
injury-related bleeding. Blood tests can help pinpoint
factor VII deficiency.

can be cleaned and bandaged. Parents of hemophiliac children receiving immunizations should inform
the vaccination provider in advance to decrease the
possibility of bleeding problems. These children
should probably not receive injections which go
into the muscle.


Treatment for disseminated intravascular coagulation patients is complicated by the large variety of
underlying causes of the disorder. If at all possible,
the physician will first treat this underlying disorder. If the patient is not already bleeding, this supportive treatment may eliminate the DIC. However,
if bleeding is occurring, the patient may need blood,
platelets, fresh frozen plasma, or other blood products. Heparin has been controversial in treating
DIC, but it is often used as a last resort to stop
hemorrhage. Heparin has not proven useful in treating patients with DIC resulting from heat stroke,
exotic snakebites, trauma, mismatched transfusions, and acute problems resulting from obstetrical
complications.



Secondary acquired thrombocytopenia is best alleviated by treating the underlying cause or disorder.
The specific treatment may depend on the underlying
cause. Sometimes, corticosteroids or immune globulin may be given to improve platelet production.



Von Willebrand’s disease is treated by several methods to reduce bleeding time and to replace factor VIII,
which consequently will replace the Von Willebrand
factor. This may include infusion of cryoprecipitate or
fresh frozen plasma. Desmopressin may also help
raise levels of the Von Willebrand factor.



Hypoprothrombinemia may be treated with concentrates of prothrombin. Vitamin K may also be produced, and in bleeding episodes, the patient may
receive fresh plasma products.



Factor XI (hemophilia C) is most often treated with
plasma, since there are no commercially available
concentrates of factor XI in the United States.
Factor VII patients may be treated with prothrombin complex concentrates. As of early 1998, factor
VII concentrate was not licensed in the United States
and could only be used with special permission.

Treatment
In mild cases, treatment may involve the use of
drugs that stimulate the release of deficient clotting
factors. In severe cases, bleeding may only stop if the
clotting factor that is missing is replaced through infusion of donated human blood in the form of fresh
frozen plasma or cryoprecipitate.


Hemophilia A in mild episodes may require infusion
of a drug called desmopressin or DDAVP. Severe
bleeding episodes will require transfusions of
human blood clotting factors. Hemophiliacs are
encouraged to receive physical therapy to help
damaged joints and to exercise in non-contact sports
such as swimming, bicycle riding, or walking.



Christmas disease patients are treated similarly to
hemophilia A patients. There are commercial products and human blood products available to provide coagulation. Cryoprecipitate was invented in
1965 to replace the need for whole plasma transfusions, which introduced more volume than needed.
By the 1970s, people were able to infuse themselves
with freeze-dried clotting factor. Superficial wounds

914

Alternative treatment
This can be a very severe condition and should be
managed by a practitioner of alternative medicine in
conjunction with a medical doctor; this condition
should not be self managed. For patients known to
suffer from hemophilia A or B and other bleeding disorders, avoidance of activities that can cause severe
GALE ENCYCLOPEDIA OF MEDICINE

Clotting factor—Also known as coagulation factors. Proteins in the plasma which serve to activate
various parts of the blood clotting process by being
transformed from inactive to active form.
Enzyme—A substance that causes a chemical reaction, usually a protein. Enzymes are secreted by
cells.
Hemorrhage—Abnormal bleeding from the blood
vessels.
Heparin—An anticoagulant, or blood clot ‘‘dissolver.’’
Idiopathic—Refers to a disease of unknown cause,
and sometime to a primary disease.
Metastatic—The term used to describe a secondary
cancer, or one that has spread from one area of the
body to another.
Serum reagents—Serum is fluid, or the fluid portion of the blood retained after removal of the
blood cells and fibrin clot. Reagents are substances added to the serum to produce a chemical
reaction.
Thrombosis—Formation of a clot in the blood that
either blocks, or partially blocks a blood vessel. The
thrombus may lead to infarction, or death of tissue,
due to a blocked blood supply.

products were subject to increased risk of AIDS and
other diseases. However, efforts have been made
since the early 1990s to ensure the safety of the
blood supply.

Prevention
Prevention of coagulation disorders varies. Acquired
disorders may only be prevented by preventing onset
of the underlying disorder (such as cirrhosis).
Hereditary disorders can be predicted with prenatal
testing and genetic counseling. Prevention of severe
bleeding episodes may be accomplished by refraining
from activities that could cause injury, such as contact
sports. Open communication with healthcare providers prior to procedures or tests that could cause
bleeding may prevent a severe bleeding incident.
Resources
PERIODICALS

Community Alert. New York: National Hemophilia
Foundation.
ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Hemophilia Foundation. 116 West 32nd St., 11th
Floor, New York, NY 10001. 800-424-2634. <http://
www.hemophilia.org/home.htm>.

Teresa Odle
injury should be practiced. Comprehensive care
addresses the whole person by helping to deal with the
psychosocial aspects of the disease.

Coagulopathies see Coagulation disorders
Coal miner’s disease see Black lung disease

Prognosis
The prognosis for patients with mild forms of
coagulation disorders is normally good. Many people
can lead a normal life and maintain a normal life
expectancy. Without treatment of bleeding episodes,
severe muscle and joint pain, and eventually, damage,
can occur. Any incident that causes blood to collect
in the head, neck, or digestive system can be very
serious and requires immediate attention. DIC can
be severe enough to cause clots to form and a stroke
could occur. DIC is also serious enough to cause
gangrene in the fingers, nose or genitals. The prognosis depends on early intervention and treatment of
the underlying condition. Hemorrhage from a coagulation disorder, particularly into the brain or digestive track, can prove fatal. In the past, patients
who received regular transfusions of human blood
GALE ENCYCLOPEDIA OF MEDICINE

Coal worker’s pneumoconiosis see Black
lung disease

I Coarctation of the aorta
Definition
A defect that develops in the fetus in which there is
a narrowing of the aortic arch, the main blood artery
that delivers blood from the left ventricle of the heart to
the rest of the body. Coarctation of the aorta is diagnosed in both newborns and adults. Approximately
10% of newborns with congenital heart disease have
coarctation of the aorta.
915

Coarctation of the aorta

KEY TERMS

Coarctation of the aorta

Description
Blood leaves the heart by way of the left ventricle
and is distributed to the body by arteries. The aortic
arch is the first artery to carry blood as it leaves the
heart. Other arteries to the head and arms branch off
the aortic arch. A narrowing of the aorta at any spot
produces resistance to the flow of blood. This causes
high blood pressure before the narrowing and low
pressure below the narrowing (downstream). Parts of
the body supplied by arteries that branch off the aortic
arch before the narrowing have high blood pressure,
while most of the lower body does not receive enough
blood supply. To compensate for this, the heart works
harder, and the blood pressure rises.
Approximately half of all infants with coarctation
of the aorta are diagnosed within the first two months of
life. Frequently, there are other congenital cardiac complications present. Infants with Turner syndrome have a
45% rate of also having coarctation. There is evidence
that some cases of coarctation may be inherited.

Causes and symptoms
In newborns with congenital heart disease, coarctation of the aorta develops while the baby is in the
womb. Among the consequences of coarctation of the
aorta is ventricular hypertrophy, an enlarging of the
left ventricle in response to the increased back pressure
of the blood and the demand for more blood by the
body. Symptoms in infants include shortness of breath
(dyspnea), difficulty in feeding, and poor weight gain.
Older children usually don’t have symptoms, but may
display fatigue, shortness of breath, or a feeling of
lameness in their legs.

Diagnosis
Infants usually have an abnormal ‘‘gallop’’ heart
rhythm and may also have heart murmurs. Sometimes
excessive arterial pulses can be seen in the carotid and
suprasternal notch arteries, indicating increased pressure in these arteries, while the femoral pulse is weak
or cannot be detected. The systolic pressure is higher in
the arms than in the legs. Enlargement of the heart can
be seen in x rays. Similar symptoms are seen in older
children and adults. A 10 mm Hg (mercury) pressure
difference between the upper and lower extremities is
diagnostic for coarctation of the aorta. For some
patients, the systolic pressure difference is observed
only during exercise. Infants frequently have an
abnormal electrocardiogram (ECG) that indicates
that the right or both ventricles are enlarged, while in
older children the ECG may be normal or show that
916

KEY TERMS
Dyspnea—Difficulty in breathing. Usually associated with heart or lung diseases.
Electrocardiogram—A graph of the heart’s beating
produced by an instrument that detects the electrical signals made by the heart.

the left ventricle is enlarged. The coarctation may be
detected in echocardiographic examination.

Treatment
Drugs can be used to treat the hypertension and
heart failure. Surgery is recommended for infants with
other, associated cardiac defects and for those infants
not responding to drug therapy. Surgery is indicated
for infants that don’t require immediate surgery, but
who develop severe hypertension during the first several months of life. Patients are advised to avoid
vigorous exercise prior to surgical correction of the
coarctation. Recoarctation can occur in some
patients, even if they have had surgery.

Prognosis
Approximately half of all infants diagnosed with
coarctation of the aorta have no other cardiac defects
and will respond well to medical management. Most of
these children will eventually outgrow the condition
after several years of life. Although their hypertension
may increase for several months early in life, it will
eventually decrease as the circulatory system develops.
Surgery is required for infants that have severe coarctation of the aorta or have associated cardiac defects.
The average life span of children who have coarctation
of the aorta is 34 years of age. The most common
complications for children who have not had surgery
are hypertension, aortic rupture, intracranial bleeding,
and congestive heart failure. Women who have an
uncorrected coarctation of the aorta have a mortality
rate of 10% during pregnancy and a 90% rate of
complications.
Resources
BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, editors. The
Heart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Cocaine is a highly addictive central nervous system stimulant extracted from the leaves of the coca
plant, Erythroxylon coca.

Description
In its most common form, cocaine is a whitish
crystalline powder that produces feelings of euphoria
when ingested.
Now classified as a Schedule II drug, cocaine has
legitimate medical uses as well as a long history of
recreational abuse. Administered by a licensed physician, the drug can be used as a local anesthetic for
certain eye and ear problems and in some kinds of
surgery.

The drug culture of the 1960s sparked renewed
interest in cocaine. With the advent of crack in the
1980s, use of the drug had once again become a
national problem. Cocaine use declined significantly
during the early 1990s, but it remains a significant
problem and is on the increase in certain geographic
areas and among certain age groups. A mid-1990s government report said that Americans spend more money
on cocaine than on all other illegal drugs combined.

Causes and symptoms
Forms of the drug
In powder form, cocaine is known by such street
names as ‘‘coke,’’ ‘‘blow,’’ ‘‘C,’’ ‘‘flake,’’ ‘‘snow’’ and
‘‘toot.’’ It is most commonly inhaled or ‘‘snorted.’’ It
may also be dissolved in water and injected.
Crack is a smokable form of cocaine that produces an immediate and more intense high. It comes
in off-white chunks or chips called ‘‘rocks.’’ Little
crumbs of crack are sometimes called ‘‘kibbles & bits.’’
In addition to their stand-alone use, both cocaine
and crack are often mixed with other substances.
Cocaine may be mixed with methcathinone (a more
recent drug of abuse, known as ‘‘cat,’’ that is similar to
methamphetamine) to create a ‘‘wildcat.’’ A hollowedout cigar filled with a mixture of crack and marijuana
is known as a ‘‘woolah.’’ And either cocaine or crack
used in conjunction with heroin is called a ‘‘speedball.’’ Cocaine used together with alcohol represents
the most common fatal two-drug combination.
History
Cocaine is one of the oldest known psychoactive
drugs. Coca leaves, the source of cocaine, were used by
the Incas and other inhabitants of the Andean region
of South America for thousands of years, both as a
stimulant and to depress appetite and combat apoxia
(altitude sickness).
Despite the long history of coca leaf use, it was not
until the latter part of the nineteenth century that the
active ingredient of the plant, cocaine hydrochloride,
was first extracted from those leaves. The new drug
GALE ENCYCLOPEDIA OF MEDICINE

As with other forms of addiction, cocaine abuse is
the result of a complex combination of internal and
external factors. Genetic predisposition, family history, and immediate environment can affect a person’s
probability of becoming addicted.
As many as three to four million people are estimated to be chronic cocaine users. The 1997 National
Household Survey on Drug Abuse reported an estimated 600,000 current crack users, showing no significant change since the late 1980s.
How cocaine affects the brain
Extensive research has been conducted to determine how cocaine works on the brain and why it is so
addictive. Cocaine has been found to affect an area of
the brain known as the ventral tegmental area (VTA),
which connects with the nucleus accumbens, a major
pleasure center. Like other commonly abused addictive drugs, cocaine’s effects are related to the action
of the neurotransmitter dopamine, which carries
information between neurons. Cocaine interferes
with the normal functioning of neurons by blocking
the re-uptake of dopamine, which builds up in
the synapses and is believed to cause the pleasurable
feelings reported by cocaine users.
Short-term effects of use
The short-term effects of cocaine can include:


rapid heartbeat



constricted blood vessels
917

Cocaine

I Cocaine

soon became a common ingredient in patent medicines
and other popular products (including the original
formula for cola). This widespread use quickly raised
concerns about the drug’s negative effects. In the early
1900s, several legislative steps were taken to address
those concerns; the Harrison Act of 1914 banned the
use of cocaine and other substances in non-prescription
products. In the wake of those actions, cocaine use
declined substantially.

Cocaine



dilated pupils



increased temperature



increased energy



reduced appetite



increased sense of alertness



euphoria



death due to overdose
Long-term effects of use

The long-term effects of cocaine and crack use
include:

problems. Supporting the cocaine-exposed expecting
mother so as to discourage cocaine use remains an
important task for all health caregivers.

Diagnosis
Diagnosing cocaine addiction can be difficult.
Many of the signs of short-term cocaine use are not
obvious. Since cocaine users often also use other
drugs, it may not be easy to distinguish the effects of
one drug from another.
Cocaine use has been documented in significant
numbers of eighth graders as well as older teens. Over
all age groups, more men than women use the drug.
The highest rate of cocaine use is found among adults
18 to 25 years old.



dependence, addiction



irritability



mood swings



restlessness



weight loss



auditory hallucinations



arrhythmia



paranoia



heart attacks



chest pain



respiratory failure



strokes



seizures

Cocaine use and pregnancy
The rise in cocaine use as well as the appearance of
crack cocaine in the late 1980s spurred fears about its
effects on the developing fetus and, since then, several
research reports have suggested that prenatal cocaine
use could be associated to a wide range of fetal, newborn, and child development problems. According to
the Lindesmith Center-Drug Policy Foundation,
many of these early reports had methodological flaws,
and most researchers nowadays propose more cautious conclusions concerning prenatal cocaine effects.
Much evidence would seem to point to the lack of
quality prenatal care and the use of alcohol and
tobacco as primary factors in poor fetal development
among pregnant cocaine users. Research sponsored by
the National Institute on Drug Abuse (NIDA) and the
Albert Einstein Medical Center in Philadelphia corroborate the Lindensmith Center findings in reporting
that the lack of quality prenatal care is associated with
undesirable effects often attributed to cocaine exposure such as prematurity, low birth weight, and fetal or
infant death. The Center for Disease Control and
Prevention (CDC), however, reports that mothers
who use cocaine early in pregnancy are five times as
likely to have a baby with a malformation of the
urinary tract as mothers who do not use the drug.
Thus, cocaine use during pregnancy is inadvisable,
especially since it is also often associated with the use
of alcohol known to cause long-term developmental
918

Medical complications
Cocaine has been linked to several serious health
problems, including:

Other complications may vary depending on how
the drug is administered. Prolonged snorting, for
example, can irritate the nasal septum, producing
nosebleeds, chronic runny nose, and other problems.
Intravenous users face an increased risk of infectious
diseases such as HIV/AIDS and hepatitis.
Testing
Drug testing can be useful in diagnosing and treating cocaine abuse. Urine testing can detect cocaine;
besides providing an objective alternative to reliance
on what a patient says, such tests can also be used as a
follow-up to treatment to confirm that the patient has
remained drug-free.

Treatment
The last two decades have seen a dramatic rise in
the number of cocaine addicts seeking treatment. But
like all forms of drug abuse, cocaine abuse/addiction is
a multifaceted phenomenon involving environmental,
social, and familial as well as physiological factors.
This greatly complicates the challenge of effectively
treating cocaine addiction.
GALE ENCYCLOPEDIA OF MEDICINE

Cocaine

Pharmacological treatments
To date, no medications have been approved specifically for treating cocaine addiction. But several
were under development at this writing. Selegeline,
delivered either via a time-release pill or a transdermal
patch, shows promise as a possible anti-cocaine medication. Clinical studies have shown the drug disulfiram (also used to treat alcoholics) to be effective in
treating cocaine abusers. In addition, antidepressant
medications are sometimes used to control the mood
swings associated with the early stages of cocaine withdrawal. Research in 2004 was looking at new
approach—treating cocaine addiction with a virus
that helped clear the drug from the brain.
Behavioral approaches
A wide range of behavioral interventions have
been successfully used to treat cocaine addiction. The
approach used must be tailored to the specific needs of
each individual patient, however.
Contingency management rewards drug abstinence (confirmed by urine testing) with points or vouchers which patients can exchange for such things as
an evening out or membership in a gym. Cognitivebehavioral therapy helps users learn to recognize and
avoid situations most likely to lead to cocaine use and
to develop healthier ways to cope with stressful situations. Residential programs/therapeutic communities
may also be helpful, particularly in more severe cases.
Patients typically spend six to 12 months in such programs, which may also include vocational training and
other features.

Alternative treatment
Various alternative or complementary approaches
have been used in treating cocaine addiction, often in
combination with more conventional therapies. In
Japan, the herb acorus has been traditionally used
both to assist early-stage cocaine withdrawal and in
later recovery stages. Other herbs sometimes used to
treat drug addictions of various kinds include kola nut,
guarana seed and yohimbe (to boost short-term
energy), and valerian root, hops leaf, scullcap leaf,
and chamomile (to calm the patient). The amino acids
phenylalanine and tyrosine have been used to reduce
cocaine addicts’ craving for the drug, and vitamin therapy may be used to help strengthen the patient. Gentle
massage has been used to help infants born with congenital cocaine addiction. Other techniques, such as
acupuncture, EEG biofeedback, and visualization, may
also be useful in treating addiction.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Apoxia—Apoxia refers to altitude sickness.
Arrhythmia—Irregular heartbeat.
Central nervous system—Part of the nervous system consisting of the brain, cranial nerves and
spinal cord. The brain is the center of higher
processes, such as thought and emotion and is
responsible for the coordination and control of
bodily activities and the interpretation of information from the senses. The cranial nerves and
spinal cord link the brain to the peripheral nervous system, that is the nerves present in the rest
of body.
Nasal septum—The membrane that separates the
nostrils.
Neurotransmitter—A chemical that carries nerve
impulses across a synapse.
Synapse—The gap between two nerve cells.

Prognosis
Because addiction involves so many different factors, prospects for individual addicts vary widely. A
2004 study found that recovered drug addicts often
crave the drug for years and are at risk for relapse.
However, research also has consistently shown that
treatment can significantly reduce both drug abuse
and subsequent criminal activity. The comprehensive
Services Research Outcomes Study (1998) found a 45%
drop in cocaine use five years after treatment, compared to use during the five years before treatment.
The study also found that females generally respond
better to treatment than males, and older patients tend
to reduce their drug use more than younger patients.
Some research also supports the idea that 12-step
programs used in conjunction with other approaches
can significantly enhance the prospects for a positive
outcome. One study of people in outpatient drugtreatment programs found that participation in a
12-step program nearly doubled their chances of
remaining drug-free.

Prevention
Despite significant variation over time, cocaine
addiction has proven to be a persistent public health
problem. Interdiction and source control are expensive and have failed to eliminate the problem, and
919

Coccidioidomycosis

some law enforcement officials are now recommending more emphasis on demand reduction through education and other measures to address the causes of
cocaine addiction.

valleys of California. Although commonly acquired,
overt coccidioidomycosis is a rare disease. Chronic
infections occur in only one out of every 100,000
people.

Resources

Although anyone can get coccidioidomycosis,
farm laborers, construction workers, and archaeologists who work where it is dusty are at greater risk to
become infected. People of any age can get coccidioidomycosis, but the disease most commonly occurs in
the 25–55 age group. In its acute form, coccidioidomycosis infects men and women equally.

PERIODICALS

Avants, S. Kelly. ‘‘A Randomized Controlled Trial of
Auricular Acupuncture for Cocaine Dependence.’’
JAMA November 22, 2000.
‘‘Craving for Cocaine May Last for Years after Recovery.’’
Health & Medicine Week April 19, 2004: 846.
Goode, Erica. ‘‘Acupuncture Helps Some Quell Need for
Cocaine.’’ New York Times August 15, 2000: D7.
LeDuff, Charlie. ‘‘Cocaine Quietly Reclaims Its Hold as
Good Times Return.’’ New York Times August 21,
2000: 2.
‘‘Treating Cocaine Addiction With Viruses.’’ Ascribe Health
News Service June 21, 2004.
ORGANIZATIONS

Cocaine Anonymous. 6125 Washington Blvd. Suite 202,
Culver City, CA 90232. (800) 347-8998.
Nar-Anon Family Group Headquarters, Inc. P.O. Box 2562,
Palos Verdes Peninsula, CA 90274. (310) 547-5800.

Peter Gregutt
Teresa G. Odle

I Coccidioidomycosis
Definition
Coccidioidomycosis is an infection caused by inhaling the microscopic spores of the fungus Coccidioides
immitis. Spores are the tiny, thick-walled structures
that fungi use to reproduce. Coccidioidomycosis exists
in three forms. The acute form produces flu-like symptoms. The chronic form can develop as many as 20 years
after initial infection and, in the lungs, can produce
inflamed, injured areas that can fill with pus (abscesses).
Disseminated coccidioidomycosis describes the type of
coccidioidomycosis that spreads throughout the body
affecting many organ systems and is often fatal.

Description
Coccidioidomycosis is an airborne infection. The
fungus that causes the disease is found in the dry desert
soil of the southwestern United States, Mexico, and
Central and South America. Coccidioidomycosis is
sometimes called San Joaquin fever, valley fever, or
desert fever because of its prevalence in the farming
920

Chronic and disseminated forms of coccidioidomycosis occur more frequently in men and pregnant
women. Although it is not clear why, people of color
are 10–20 times more likely to develop the disseminated
form of the disease than caucasians. People who have a
weakened immune system (immunocompromised),
either from diseases such as AIDS or leukemia, or as
the result of medications that suppressed the immune
system (corticosteroids, chemotherapy), are more likely
to develop disseminated coccidioidomycosis.

Causes and symptoms
When the spores of C. immitis are inhaled, they
can become lodged in the lungs, divide, and cause
localized inflammation. This is known as acute or
primary coccidioidomycosis. The disease is not spread
from one person to another. Approximately 60% of
people who are infected exhibit no symptoms (asymptomatic). In the other 40%, symptoms appear 10–30
days after exposure. These symptoms include a fever
which can reach 104  F (39.5  C), dry cough, chest
pains, joint and muscle aches, headache, and weight
loss. About two weeks after the start of the fever, some
people develop a painful red rash or lumps on the
lower legs. Symptoms usually disappear without treatment in about one month. People who have been
infected gain partial immunity to reinfection.
The chronic form of coccidioidomycosis normally
occurs after a long latent period of 20 or more years
during which the patient experiences no symptoms of
the disease. In the chronic phase, coccidioidomycosis
causes lung abscesses that rupture, spilling pus and
fluid into the lungs, and causing serious damage to
the lungs. The patient experiences difficulty breathing
and has a fever, chest pain, and other signs of pneumonia. Medical treatment is essential for recovery.
In its disseminated form, coccidioidomycosis
spreads to other parts of the body including the liver,
bones, skin, brain, heart, and lining around the heart
(pericardium). Symptoms include fever, joint pain,
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Many cases of coccidioidomycosis go undiagnosed because the symptoms resemble those of common viral diseases. However, a skin test similar to that
for tuberculosis will determine whether a person has
been infected. The test is simple and accurate, but it
does not indicate whether the disease was limited to its
acute form or if it has progressed to its chronic form.
Diagnosis of chronic or disseminated coccidioidomycosis is made by culturing a sample of sputum or
other body fluids in the laboratory to isolate the fungus. A blood serum test is used to detect the presence
of an antibody produced in response to C. immitis
infection. Chest x rays are often used to assess lung
damage, but alone cannot lead to a definitive diagnosis of coccidioidomycosis because other diseases can
produce similar results on the x ray.

Treatment
In most cases of acute coccidioidomycosis, the
body’s own immune system is adequate to bring
about recovery without medical intervention. Fever
and pain can be treated with non-prescription drugs.
Chronic and disseminated coccidioidomycosis,
however, are serious diseases that require treatment
with prescription drugs. Patients with intact immune
systems who develop chronic coccidiodomycosis are
treated with the drug ketoconazole (Nizoral) or
amphotericin B (Fungizone). Patients with suppressed
immune systems are treated with amphotericin B
(Fungizone). Amphotericin B is a powerful fungistatic
drug with potentially toxic side effects. As a result,
hospitalization is required in order to monitor
patients. The patient may also receive other drugs to
minimize the side effects of the amphotericin B.
Patients with AIDS must continue to take itraconazole (Sporonox) or fluconazole (Diflucan) orally
or receive weekly intravenous doses of amphotericin
B for the rest of their lives in order to prevent a
relapse. Because of the high cost of fluconazole,
Pfizer, the manufacturer of the drug, has established
a financial assistance plan to make the drug available
at lower cost to those who meet certain criteria.
Patients needing this drug should ask their doctors
about this program.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Abscess—An area of inflamed and injured body
tissue that fills with pus.
Acidophilus—The bacteria Lactobacillus acidophilus that usually found in yogurt.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Antigen—A foreign protein to which the body
reacts by making antibodies.
Asymptomatic—Persons who carry a disease but
who do not exhibit symptoms of the disease are
said to be asymptomatic.
Bifidobacteria—A group of bacteria normally present in the intestine. Commercial supplements containing these bacteria are available.
Corticosteroids—A group of hormones produced
naturally by the adrenal gland or manufactured
synthetically. They are often used to treat inflammation. Examples include cortisone and prednisone.
Immunocompromised—A state in which the immune system is suppressed or not functioning properly.
Meningitis—An inflammation of the membranes
surrounding the brain or spinal cord.
Pericardium—The tissue sac around the heart.

Alternative treatment
Alternative treatment for fungal infections
focuses on creating an internal environment where
the fungus cannot survive. This is accomplished by
eating a diet low in dairy products, sugars, including
honey and fruit juice, and foods like beer that contain
yeast. This is complemented by a diet consisting, in
large part, of uncooked and unprocessed foods.
Supplements of vitamins C, E, A-plus, and B complex
may also be useful. Lactobacillus acidophilus and
Bifidobacterium will replenish the good bacteria in
the intestines. Antifungal herbs, like garlic (Allium
sativum), can be consumed in relatively large does
and for an extended period of time in order to increase
effectiveness.

Prognosis
Most people who are infected with coccidiodomycosis only suffer from the mild, acute form of the
disease and recover without further complications.
921

Coccidioidomycosis

loss of appetite, weight loss, night sweats, skin lesions,
and difficulty breathing. Also, in 30–50% of patients
with disseminated coccidioidomycosis, the tissue coverings of the brain and spinal cord become inflamed
(meningitis).

Coccyx injuries

Patients who suffer from chronic coccidiodomycosis
and who have no underlying lung or immune system
diseases also stand a good change of recovery,
although they must be alert to a relapse.
The picture for patients with the disseminated
form of the disease, many of whom have AIDS, is
less positive. Untreated disseminated coccidiodomycosis is almost always fatal within a short time. With
treatment, chance of survival increases, but the death
rate remains high when meningitis or diffuse lung
(pulmonary) disease is present. AIDS patients must
constantly guard against relapse.

Prevention
Because the fungus that causes coccidioidomycosis is airborne and microscopic, the only method
of prevention is to avoid visiting areas where it is
found in the soil. Unfortunately, for many people
this is impractical. Maintaining general good health
and avoiding HIV infection will limit coccidioidomycosis to the acute and relatively mild form in most
people.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
Canadian HIV/AIDS Clearinghouse. 1565 Carling Avenue,
Suite 400, Ottawa, ON K1Z 8R1. (877) 999-7740.
<http://www.clearinghouse.cpha.ca/
clearinghouse_e.htm>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
National Aids Hotline. (800) 342-2437.
Project Inform. 205 13th Street, #2001, San Francisco, CA
94103. (800) 822-7422. <http://www.projinf.org>.

Tish Davidson, A.M.

Description
The coccyx consists of fused vertebrae, which are
not flexible like the other vertebrae of the vertebral
column which are all interspaced by intervertebral
disks and joined together by elastic ligaments. Since
the spinal cord ends just before the coccyx begins,
coccygeal vertebrae also lack a central foramen
(hole). In the coccyx, the vertebrae generally fuse
together in early adulthood and may also fuse with
the sacrum, the bone located between the fifth lumbar
vertebra and the coccyx, as a person ages. In males, the
coccyx curves downward, and in females, it is straighter to allow a baby to pass through the birth canal
without impediment.
Pain in or around the coccyx is called coccydynia
or coccygodynia. Coccydynia presents a range of
symptoms associated to a variety of underlying causes
and conditions.

Causes and symptoms
Causes
Coccydynia can be caused by a number of factors.
Usually, patients report pain after a fall onto their
buttocks, as occurs when going down stairs or while
skating. Others have pain during pregnancy or after
childbirth. Some experience repetitive strain from rowing or cycling, and some cite anal intercourse as the
cause of pain. In many cases, pain derives from a
malformation of the coccyx itself. Sometimes bony
spurs appear on the coccyx, but only seem to be painful in thin patients who do not have the padding to
protect the region from the spur.
Other causes of coccydynia include cancer or
damage to the sacrum that generates referred pain,
meaning pain that appears in one region but originates
from another. Muscle strain or tension, pinched
nerves or damaged nerves, or dislocation of the coccyx
due to gross obesity are other causes.
Symptoms

I Coccyx injuries
Definition
The coccyx—or tailbone—is the last bone of the
vertebral column, and usually consists of three to five
fused vertebrae that connect with the sacrum, a part of
the pelvis.
922

The most common symptom of coccydynia, irrespective of the cause of the condition, is pain when
sitting, or when rising from a sitting position. If the
condition lasts long enough, the patient may even
experience pain when standing or lying down.
Sometimes, numbness occurs in the lower part of the
spine. Some patients will experience pain during bowel
movements, sexual intercourse, or menstruation.
Secondary symptoms include back pain from sitting in odd positions in order to relieve pain, and
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Diagnosis of fracture is usually made by inserting
a gloved finger in the rectum and pressing on the
coccyx. X rays and magnetic resonance imaging
(MRI) are also often used. Since coccyx pain may be
the result of other factors like cancer, these must be
ruled out through a variety of tests before treatment
can begin.

Treatment
Treatment exists to either control the pain or
eliminate the cause. Pain control may be dangerous if
an underlying condition exists of which the pain is a
warning sign. Nerve blocks and a variety of drugs are
other options to control pain.
Elimination of the root cause of the pain is ideal.
This is done through careful diagnosis and the application of manual treatments, corticosteroid injections
into the coccyx vertebrae, or surgery. Injections into
the fourth and fifth sacral nerves and coccygeal nerves
often bring relief, but are considered more as a pain
control measure than as curative treatment. Manual
treatments have not been found to be effective.
Surgery is a radical procedure whose indications are
inconsistent and dependent on the subjectivity of the
physician.

Prognosis

KEY TERMS
Coccyx—The last bone of the spinal column, consisting of three to five fused vertebrae that connect
with the sacrum, a part of the pelvis.
Coccydynia—Also called coccygodynia. Pain in or
around the coccyx.
Foramen—A small opening, perforation, or orifice.
Magnetic resonance imaging (MRI)—An imaging
technique that produces pictures of the inside of
the body.
Sacrum—The triangle-shaped bone located
between the fifth lumbar vertebra and the coccyx
that consists of five vertebrae fused together. The
sacrum joins on each side with the bones of the
pelvis.
Spinal cord—Elongated nerve bundles that lie in
the vertebral canal and from which the spinal
nerves emerge.
Vertebrae—Bones in the cervical, thoracic, and
lumbar regions of the body that make up the vertebral column. Vertebrae have a central foramen
(hole), and their superposition makes up the
vertebral canal that encloses the spinal cord.
Vertebral column—The vertebral column, also
called the spinal column or spine, consists of a
series of vertebrae connected by ligaments. It provides a supporting axis for the body and protects
the spinal cord. The vertebral column consists of
seven cervical vertebrae in the neck, followed by
12 thoracic vertebrae that connect to the ribs, five
lumbar vertebrae in the lower back, the sacrum,
and the coccyx.

With current treatment, prognosis is good and
patients usually are able to live pain free.

Prevention

‘‘What is Coccydynia?’’ May 7, 2001. <http://www.coccyx.
org/whatisit.htm>.

There probably is no real prevention, expect
weight control. Some women may choose to give
birth through ceasarian section instead of vaginally
after an episode of coccyx pain from a previous
delivery.
Resources
OTHER

Maigne, Jean-Yves. ‘‘Treatment Strategies for Coccydynia.’’
May 7, 2001. <http://www.coccyx.org/whatisit.htm>.
‘‘Treatments for Coccydynia.’’ May 7, 2001. <http://
www.coccyx.org/treatment.htm>.

GALE ENCYCLOPEDIA OF MEDICINE

Janie F. Franz

I Cochlear implants
Definition
A cochlear implant is a surgical treatment for
hearing loss that works like an artificial human cochlea
in the inner ear, helping to send sound from the ear to
923

Cochlear implants

painful feet from standing too much, because patients
avoid sitting. Sometimes the entire buttocks experience pain. Rarely, exhaustion, depression, and lack
of sleep may occur.

Cochlear implants

the brain. It is different from a hearing aid, which
simply amplifies sound.

Purpose
A cochlear implant bypasses damaged hair cells
and helps establish some degree of hearing by stimulating the hearing (auditory) nerve directly.

Precautions
Because the implants are controversial, very
expensive, and have uncertain results, the U.S. Food
and Drug Administration (FDA) has limited the
implants to people:


who get no significant benefit from hearing aids



who are at least two years old (the age at which
specialists can verify severity of deafness)



with severe to profound hearing loss

Description
Hearing loss is caused by a number of different
problems that occur either in the hearing nerve or
parts of the middle or inner ear. The most common
type of deafness is caused by damaged hair cells in the
cochlea, the hearing part of the inner ear. Normally,
hair cells stimulate the hearing nerve, which transmits
sound signals to the brain. When hair cells stop functioning, the hearing nerve remains unstimulated, and
the person cannot hear. Hair cells can be destroyed by
many things, including infection, trauma, loud noise,
aging, or birth defects.
All cochlear implants consist of a microphone
worn behind the ear that picks up sound and sends it
along a wire to a speech processor, which is worn in a
small shoulder pouch, pocket, or belt. The processor
boosts the sound, filters out background noise, and
turns sound into digital signals before sending it to a
transmitter worn behind the ear. A magnet holds the
transmitter in place through its attraction to the receiver-stimulator, a part of the device that is surgically
attached beneath the skin in the skull. The receiver
picks up digital signs forwarded by the transmitter,
and converts them into electrical impulses. These electrical impulses flow through electrodes contained in a
narrow, flexible tube that has been threaded into the
cochlea.
As many as 24 electrodes (depending on the type
of implant) carry the impulses that stimulate the hearing nerve. The brain then interprets the signals as
specific sounds.
924

A close-up view of a cochlear implant. (Photograph by
L. Steinmark, Custom Medical Stock Photo. Reproduced by
permission.)

Despite the benefits that the implant appears to
offer, some hearing specialists and members of the
deaf community still believe that the benefits may
not outweigh the risks and limitations of the device.
Because the device must be surgically implanted, it
carries some surgical risk. Also, manufacturers cannot
promise how well a person will hear with an implant.
Moreover, after getting an implant, some people say
they feel alienated from the deaf community, while at
the same time not feeling fully a part of the hearing
world.
The sounds heard through an implant are different from the normal hearing sounds, and have been
described as artificial or ‘‘robotlike.’’ This is because
the implant’s handful of electrodes cannot hope to
match the complexity of a person’s 15,000 hair cells.
Surgical procedure
During the procedure, the surgeon makes an incision behind the ear and opens the mastoid bone (the
ridge on the skull behind the ear) leading into the
middle ear. The surgeon then places the receiverstimulator in the bone, and gently threads the electrodes into the cochlea. This operation takes between one
and one-half to five hours.

Preparation
Before a person gets an implant, specialists at an
implant clinic conduct a careful evaluation, including
extensive hearing tests to determine how well the candidate can hear.
Unfortunately, it is not possible to predict who
will benefit from an implant. In general, the later in life
GALE ENCYCLOPEDIA OF MEDICINE

First, candidates undergo a trial with a powerful
hearing aid. If the aid cannot improve hearing enough,
a physician then performs a physical exam and orders a
scan of the inner ear (some patients with a scarred
cochlea are not good candidates). A doctor may also
order a psychological exam to better understand the
person’s expectations. Patients need to be highly motivated, and have a realistic understanding of what an
implant can and cannot do.

Aftercare
The patient remains in the hospital for a day or
two after the surgery. After a month, the surgical
wounds will have healed and the patient returns to
the implant clinic to be fitted with the external parts
of the device (the speech processor, microphone, and
transmitter). A clinicican tunes the speech processor
and sets levels of stimulation for each electrode, from
soft to loud.
The patient is then trained in how to interpret the
sounds heard through the device. The length of the
training varies from days to years, depending on how
well the person can interpret the sounds heard through
the device.

Risks
As with all operations, there are a few risks of
surgery. These include:


dizziness



facial paralysis (rarely)



infection at the incision site

Scientists are not sure about the long-term effects
of electrical stimulation on the nervous system. It is
also possible to damage the implant’s internal components by a blow to the head, which will render the
device unworkable.

Normal results
Most profoundly, deaf patients who receive an
implant are able to discern medium and loud sounds,
including speech, at comfortable listening levels.
Many use sound clues from the implant, together
with speech reading and other facial cues. Almost all
adults improve their communication skills when
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cochlea—The hearing part of the inner ear. This
snail-shaped structure contains fluid and thousands
of microscopic hair cells tuned to various
frequencies.
Hair cells—Sensory receptors in the inner ear that
transform sound vibrations into messages that travel to the brain.
Inner ear—The interior section of the ear, where
sound vibrations and information about balance
are translated into nerve impulses.
Middle ear—The small cavity between the eardrum
and the oval window that houses the three tiny
bones of hearing.

combining the implant with speech reading (lip reading), and some can understand spoken words without
speech reading. More than half of adults who lost
hearing after they learned to speak can understand
some speech without speech reading. About 30% can
understand spoken sounds well enough to use the
phone.
Children who were born deaf or who lost their
hearing before they could speak have the most difficulty in learning to use the implant. Research suggests,
however, that most of these children are able to learn
spoken language and understand speech using the
implant.
Resources
ORGANIZATIONS

Alexander Graham Bell Association for the Deaf. 3417
Volta Place NW, Washington, DC 20007. (202) 3375220. <http://www.agbell.org>.
American Speech-Language-Hearing Association. 10801
Rockville Pike, Rockville, MD 20852. (800) 638-8255.
<http://www.asha.org>.
Cochlear Implant Club International. 5335 Wisconsin Ave.
NW, Suite 440, Washington, DC 20015-2052. (202)
895-2781. <http://www.cici.org>.
Hearing Loss Link. 2600 W. Peterson Ave., Ste. 202,
Chicago, IL 60659. (312) 743-1032, (312) 743-1007
(TDD).
National Association for the Deaf. 814 Thayer Ave., Silver
Spring, MD 20910. (301) 587-1788, (301) 587-1789
(TDD). <http://www.nad.org>.

Carol A. Turkington
925

Cochlear implants

a person becomes deaf, and the shorter the duration of
deafness, the better the person is likely to understand
speech with an implant. Likewise, someone with a
healthy hearing nerve will do better than someone
with a damaged nerve.

Cognitive-behavioral therapy

I Cognitive-behavioral therapy
Definition
Cognitive-behavioral therapy is an action-oriented
form of psychosocial therapy that assumes that maladaptive, or faulty, thinking patterns cause maladaptive
behavior and ‘‘negative’’ emotions. (Maladaptive behavior is behavior that is counter-productive or interferes
with everyday living.) The treatment focuses on changing an individual’s thoughts (cognitive patterns) in
order to change his or her behavior and emotional
state.

Purpose
Theoretically, cognitive-behavioral therapy can
be employed in any situation in which there is a pattern of unwanted behavior accompanied by distress
and impairment. It is a recommended treatment
option for a number of mental disorders, including
affective (mood) disorders, personality disorders,
social phobia, obsessive-compulsive disorder (OCD),
eating disorders, substance abuse, anxiety or panic disorder, agoraphobia, post-traumatic stress disorder
(PTSD), and attention-deficit/hyperactivity disorder
(ADHD). It is also frequently used as a tool to deal
with chronic pain for patients with illnesses such as
rheumatoid arthritis, back problems, and cancer.
Patients with sleep disorders may also find cognitivebehavioral therapy a useful treatment for insomnia.

that maladaptive behaviors and disturbed mood or
emotions are the result of inappropriate or irrational
thinking patterns, called automatic thoughts. Instead
of reacting to the reality of a situation, an individual
reacts to his or her own distorted viewpoint of the
situation. For example, a person may conclude that
he is ‘‘worthless’’ simply because he failed an exam or
did not get a date. Cognitive therapists attempt to
make their patients aware of these distorted thinking
patterns, or cognitive distortions, and change them
(a process termed cognitive restructuring).
Behavioral therapy, or behavior modification,
trains individuals to replace undesirable behaviors
with healthier behavioral patterns. Unlike psychodynamic therapies, it does not focus on uncovering or
understanding the unconscious motivations that may
be behind the maladaptive behavior. In other words,
strictly behavioral therapists do not try to find out why
their patients behave the way they do, they just teach
them to change the behavior.

Cognitive-behavioral therapy combines the individual goals of cognitive therapy and behavioral therapy.

Cognitive-behavioral therapy integrates the cognitive restructuring approach of cognitive therapy
with the behavioral modification techniques of behavioral therapy. The therapist works with the patient to
identify both the thoughts and the behaviors that are
causing distress, and to change those thoughts in order
to readjust the behavior. In some cases, the patient
may have certain fundamental core beliefs, called
schemas, which are flawed and require modification.
For example, a patient suffering from depression may
be avoiding social contact with others, and suffering
considerable emotional distress because of his isolation. When questioned why, the patient reveals to his
therapist that he is afraid of rejection, of what others
may do or say to him. Upon further exploration with
his therapist, they discover that his real fear is not
rejection, but the belief that he is hopelessly uninteresting and unlovable. His therapist then tests the reality of that assertion by having the patient name
friends and family who love him and enjoy his company. By showing the patient that others value him,
the therapist both exposes the irrationality of the
patient’s belief and provides him with a new model
of thought to change his old behavior pattern. In this
case, the person learns to think, ‘‘I am an interesting
and lovable person; therefore I should not have difficulty making new friends in social situations.’’ If
enough ‘‘irrational cognitions’’ are changed, this
patient may experience considerable relief from his
depression.

Pioneered by psychologists Aaron Beck and
Albert Ellis in the 1960s, cognitive therapy assumes

A number of different techniques may be
employed in cognitive-behavioral therapy to help

Precautions
Cognitive-behavioral therapy may not be suitable
for some patients. Those who do not have a specific
behavioral issue they wish to address and whose goals
for therapy are to gain insight into the past may be
better served by psychodynamic therapy. Patients
must also be willing to take a very active role in the
treatment process.
Cognitive-behavioral intervention may be inappropriate for some severely psychotic patients and
for cognitively impaired patients (for example,
patients with organic brain disease or a traumatic
brain injury), depending on their level of functioning.

Description

926

GALE ENCYCLOPEDIA OF MEDICINE



Behavioral homework assignments. Cognitive-behavioral therapists frequently request that their
patients complete homework assignments between
therapy sessions. These may consist of real-life
‘‘behavioral experiments’’ where patients are encouraged to try out new responses to situations discussed
in therapy sessions.



Cognitive rehearsal. The patient imagines a difficult
situation and the therapist guides him through the
step-by-step process of facing and successfully dealing with it. The patient then works on practicing, or
rehearsing, these steps mentally. Ideally, when the
situation arises in real life, the patient will draw on
the rehearsed behavior to address it.



Journal. Patients are asked to keep a detailed diary
recounting their thoughts, feelings, and actions when
specific situations arise. The journal helps to make
the patient aware of his or her maladaptive thoughts
and to show their consequences on behavior. In later
stages of therapy, it may serve to demonstrate and
reinforce positive behaviors.



Modeling. The therapist and patient engage in roleplaying exercises in which the therapist acts out
appropriate behaviors or responses to situations.



Conditioning. The therapist uses reinforcement to
encourage a particular behavior. For example, a
child with ADHD gets a gold star every time he
stays focused on tasks and accomplishes certain
daily chores. The gold star reinforces and increases
the desired behavior by identifying it with something
positive. Reinforcement can also be used to extinguish unwanted behaviors by imposing negative
consequences.



Systematic desensitization. Patients imagine a situation they fear, while the therapist employs techniques
to help the patient relax, helping the person cope with
their fear reaction and eventually eliminate the anxiety
altogether. For example, a patient in treatment for
agoraphobia, or fear of open or public places, will
relax and then picture herself on the sidewalk outside
of her house. In her next session, she may relax herself
and then imagine a visit to a crowded shopping mall.
The imagery of the anxiety-producing situations gets
progressively more intense until, eventually, the therapist and patient approach the anxiety-causing situation in real-life (a ‘‘graded exposure’’), perhaps by
visiting a mall. Exposure may be increased to the
point of ‘‘flooding,’’ providing maximum exposure
to the real situation. By repeatedly pairing a desired
response (relaxation) with a fear-producing situation

GALE ENCYCLOPEDIA OF MEDICINE

(open, public spaces), the patient gradually becomes
desensitized to the old response of fear and learns to
react with feelings of relaxation.


Validity testing. Patients are asked to test the validity
of the automatic thoughts and schemas they encounter. The therapist may ask the patient to defend or
produce evidence that a schema is true. If the patient
is unable to meet the challenge, the faulty nature of
the schema is exposed.

Initial treatment sessions are typically spent
explaining the basic tenets of cognitive-behavioral therapy to the patient and establishing a positive working
relationship between therapist and patient. Cognitivebehavioral therapy is a collaborative, action-oriented
therapy effort. As such, it empowers the patient by
giving him an active role in the therapy process and
discourages any overdependence on the therapist that
may occur in other therapeutic relationships. Therapy
is typically administered in an outpatient setting in
either an individual or group session. Therapists
include psychologists (Ph.D., Psy.D., Ed.D. or M.A.
degree), clinical social workers (M.S.W., D.S.W., or
L.S.W. degree), counselors (M.A. or M.S. degree), or
psychiatrists (M.D. with specialization in psychiatry)
and should be trained in cognitive-behavioral techniques, although some brief cognitive-behavioral interventions may be suggested by a primary physician/
caregiver. Treatment is relatively short in comparison
to some other forms of psychotherapy, usually lasting
no longer than 16 weeks. Many insurance plans provide
reimbursement for cognitive-behavioral therapy services. Because coverage is dependent on the disorder
or illness the therapy is treating, patients should check
with their individual plans.
Rational-emotive behavior therapy
Rational-emotive behavior therapy (REBT) is a
popular variation of cognitive-behavioral therapy
developed in 1955 by psychologist Albert Ellis.
REBT is based on the belief that a person’s past
experiences shape their belief system and thinking
patterns. People form illogical, irrational thinking patterns that become the cause of both their negative
emotions and of further irrational ideas. REBT
focuses on helping patients discover these irrational
beliefs that guide their behavior and replace them with
rational beliefs and thoughts in order to relieve their
emotional distress.
There are 10 basic irrational assumptions that
trigger maladaptive emotions and behaviors:


It is a necessity for an adult to be loved and approved
of by almost everyone for virtually everything.
927

Cognitive-behavioral therapy

patients uncover and examine their thoughts and
change their behaviors. They include:

Cognitive-behavioral therapy





A person must be thoroughly competent, adequate,
and successful in all respects.
Certain people are bad, wicked, or villainous and
should be punished for their sins.



It is catastrophic when things are not going the way
one would like.



Human unhappiness is externally caused. People
have little or no ability to control their sorrows or
to rid themselves of negative feelings.



It is right to be terribly preoccupied with and upset
about something that may be dangerous or fearsome.



It is easier to avoid facing many of life’s difficulties
and responsibilities than it is to undertake more
rewarding forms of self-discipline.



The past is all-important. Because something once
strongly affected someone’s life, it should continue to
do so indefinitely.



People and things should be different from the way
they are. It is catastrophic if perfect solutions to the
grim realities of life are not immediately found.



Maximal human happiness can be achieved by inertia
and inaction or by living passively and without
commitment.
Meichenbaum’s self-instructional approach

Psychologist Donald Meichenbaum pioneered the
self-instructional, or ‘‘self-talk,’’ approach to cognitivebehavioral therapy in the 1970s. This approach focuses
on changing what people say to themselves, both
internally and out loud. It is based on the belief that
an individual’s actions follow directly from this selftalk. This type of therapy emphasizes teaching patients
coping skills that they can use in a variety of situations
to help themselves. The technique used to accomplish
this is self-instructional inner dialogue, a method of
talking through a problem or situation as it occurs.

KEY TERMS
Automatic thoughts—Thoughts that automatically
come to mind when a particular situation occurs.
Cognitive-behavioral therapy seeks to challenge
automatic thoughts.
Cognitive restructuring—The process of replacing
maladaptive thought patterns with constructive
thoughts and beliefs.
Maladaptive—Unsuitable or counterproductive;
for example, maladaptive behavior is behavior
that is inappropriate to a given situation.
Psychodynamic therapy—A therapeutic approach
that assumes dysfunctional or unwanted behavior
is caused by unconscious, internal conflicts and
focuses on gaining insight into these motivations.
Relaxation technique—A technique used to
relieve stress. Exercise, biofeedback, hypnosis,
and meditation are all effective relaxation tools.
Relaxation techniques are used in cognitive-behavioral therapy to teach patients new ways of coping
with stressful situations.
Schemas—Fundamental core beliefs or assumptions that are part of the perceptual filter people
use to view the world. Cognitive-behavioral therapy seeks to change maladaptive schemas.

opportunity to find out important details about the
therapist’s approach to treatment, professional credentials, and any other issues of interest.
In some managed-care clinical settings, an intake
interview or evaluation is required before a patient
begins therapy. The intake interview is used to evaluate the patient and assign him or her to a therapist. It
may be conducted by a psychiatric nurse, counselor, or
social worker.

Preparation
Patients may seek therapy independently, or be
referred for treatment by a primary physician, psychologist, or psychiatrist. Because the patient and
therapist work closely together to achieve specific
therapeutic objectives, it is important that their working relationship is comfortable and their goals are
compatible. Prior to beginning treatment, the patient
and therapist should meet for a consultation session,
or mutual interview. The consultation gives the therapist the opportunity to make an initial assessment of
the patient and recommend a course of treatment
and goals for therapy. It also gives the patient an
928

Normal results
Many patients who undergo cognitive-behavioral
therapy successfully learn how to replace their maladaptive thoughts and behaviors with positive ones that
facilitate individual growth and happiness. Cognitivebehavioral therapy may be used in conjunction with
pharmaceutical and other treatment interventions, so
overall success rates are difficult to gauge. However,
success rates of 65% or more have been reported with
cognitive-behavioral therapy alone as a treatment for
panic attacks and agoraphobia. Relapse has been
reported in some patient populations, perhaps due to
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

Albert Ellis Institute. 45 East 65th St., New York, NY
10021. (800) 323-4738. <http://www.rebt.org>.
Beck Institute. GSB Building, City Line and Belmont
Avenues, Suite 700, Bala Cynwyd, PA 19004-1610.
(610) 664-3020. <http://www.beckinstitute.org>.
National Association of Cognitive-Behavioral Therapists.
P.O. Box 2195, Weirton, WV 26062. (800) 853-1135.
<http://www.nacbt.org>.

Paula Anne Ford-Martin

Colchicine see Gout drugs
COLD see Chronic obstructive lung disease

I Cold agglutinins test
Definition
The cold agglutinins test is performed to detect the
presence of antibodies in blood that are sensitive to
temperature changes. Antibodies are proteins produced by the immune system in response to specific
disease agents; autoantibodies are antibodies that the
body produces against one of its own substances. Cold
agglutinins are autoantibodies that cause red blood
cells to clump, but only when the blood is cooled
below the normal body temperature of 98.6  F
(37  C). The clumping is most pronounced at temperatures below 78  F (25.6  C).

Purpose
The cold agglutinins test is used to confirm the
diagnosis of certain diseases that stimulate the body to
produce cold agglutinins. The disease most commonly
diagnosed by this test is mycoplasmal pneumonia, but
mononucleosis, mumps, measles, scarlet fever, some
parasitic infections, cirrhosis of the liver, and some
types of hemolytic anemia can also cause the formation
of cold agglutinins. Hemolytic anemias are conditions
in which the blood is low in oxygen because the red
blood cells are breaking down at a faster rate than their
normal life expectancy of 120 days. In addition to these
illnesses, some people have a benign condition called
chronic cold agglutinin disease, in which exposure to
cold causes temporary clumping of red blood cells and
consequent numbness in ears, fingers, and toes.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Agglutinin—An antibody that causes red blood
cells to stick or clump together.
Antibody—A protein molecule produced by the
immune system that is specific to a disease agent,
such as Mycoplasma pneumoniae. The antibody
combines with the organism and disables it.
Autoantibody—An antibody produced by the body
in reaction to any of its own cells or cell products.
Cold agglutinins—Antibodies that cause clumping
of red blood cells when the blood temperature falls
below normal body temperature (98.6  F/37  C).
Hemolytic anemia—Oxygen deficiency in the
blood, caused by shortened survival of red blood
cells.
Mycoplasma—A type of free-living microorganism
that has no cell wall. Mycoplasmas cause some
varieties of pneumonia and urinary tract infections
that stimulate the body to produce cold agglutinins.
Titer—The concentration of a substance in a given
sample of blood or other tissue fluid.

Description
Since cold agglutinins cause red blood cells to
clump only at temperatures lower than 98.6  F (37  C),
the test consists of chilling a sample of the patient’s
blood. There is a bedside version of the test in which
the doctor collects four or five drops of blood in a small
tube, cools the tube in ice water for 30–60 seconds, and
looks for clumping of red blood cells. If the cells clump
after chilling and unclump as they rewarm, a cold agglutinin titer (concentration) greater than 1:64 is present.
Bedside test results, however, should be confirmed by a
laboratory. The laboratory test measures the clumping
of red blood cells in different dilutions of the patient’s
blood serum at 39.2  F (4  C).

Normal results
The results of the cold agglutinins test require a
doctor’s interpretation. In general, however, a normal
value is lower than 1:32.

Abnormal results
Any value higher than 1:32 suggests a diagnosis of
mycoplasmal pneumonia or one of the other viral
infections or disease conditions indicated by this test.
929

Cold agglutinins test

the brief nature of the therapy, but follow-up sessions
can put patients back on track.

Cold sore

Resources
BOOKS

Dabrow, Michael B., and Thomas G. Gabuzda. ‘‘Acquired
Hemolytic Anemia.’’ In Current Diagnosis, edited by
Rex B. Conn, et al. Vol. 9. Philadelphia: W. B. Saunders
Co., 1997.

Rebecca J. Frey, PhD

Cold sensitivity antibodies test see
Cryoglobulin test

I Cold sore
Definition
A cold sore is a fluid-filled blister which usually
appears at the edge of the lips. Cold sores are caused
by a herpes simplex virus infection.

Description
A cold sore is a fluid-filled, painful blister that is
usually on or around the lips. Other names for a cold
sore are fever blister, oral herpes, labial herpes, herpes
labialis, and herpes febrilis. Cold sores most often
occur on the lips which distinguishes them from
the common canker sore which is usually inside the
mouth. Cold sores do not usually occur inside the
mouth except during the initial episode. Canker sores
usually form either on the tongue or inside the cheeks.
Cold sores are caused by a herpes virus. There are
eight different kinds of human herpes viruses. Only
two of these, herpes simplex types 1 and 2, can cause
cold sores. It is commonly believed that herpes simplex
virus type 1 infects above the waist and herpes simplex
virus type 2 infects below the waist. This is not completely true. Both herpes virus type 1 and type 2 can
cause herpes lesions on the lips or genitals, but recurrent cold sores are almost always type 1.
Oral herpes is very common. More than 60% of
Americans have had a cold sore, and almost 25% of
those infected experience recurrent outbreaks. Most
of these persons became infected before age 10. Anyone
can become infected by herpes virus and, once
infected, the virus remains latent for life. Herpes
viruses are spread from person to person by direct
skin-to-skin contact. The highest risk for spreading
the virus is the time period beginning with the appearance of blisters and ending with scab formation.
However, infected persons need not have visible
930

blisters to spread the infection to others since the virus
may be present in the saliva without obvious oral
lesions.
Viruses are different from bacteria. While bacteria
are independent and can reproduce on their own,
viruses enter human cells and force them to make
more virus. The infected human cell is usually killed
and releases thousands of new viruses. The cell death
and resulting tissue damage causes the actual cold
sores. In addition, the herpes virus can infect a cell
and, instead of making the cell produce new viruses, it
hides inside the cell and waits. The herpes virus hides
in the nervous system. This is called ‘‘latency.’’ A
latent virus can wait inside the nervous system for
days, months, or even years. At some future time, the
virus ‘‘awakens’’ and causes the cell to produce thousands of new viruses that cause an active infection.
This process of latency and active infection is best
understood by considering the cold sore cycle. An
active infection is obvious because cold sores are present. The first infection is called the ‘‘primary’’ infection. This active infection is then controlled by the
body’s immune system and the sores heal. In between
active infections, the virus is latent. At some point in
the future, latent viruses become activated and once
again cause sores. These are called ‘‘recurrent’’ infections. Although it is unknown what triggers latent
virus to activate, several conditions seem to bring on
infections. These include stress, illness, tiredness,
exposure to sunlight, menstruation, fever, and diet.

Causes and symptoms
While anyone can be infected by herpes virus, not
everyone will show symptoms. The first symptoms of
herpes occur within two to 20 days after contact with
an infected person. Symptoms of the primary infection
are usually more severe than those of recurrent infections. The primary infection can cause symptoms like
other viral infections including tiredness, headache,
fever, and swollen lymph nodes in the neck.
Typically, 50 to 80% of persons with oral herpes
experience a prodrome (symptoms of oncoming disease) of pain, burning, itching, or tingling at the site
where blisters will form. This prodrome stage may last
anywhere from a few hours to one to two days. The
herpes infection prodrome occurs in both the primary
infection and recurrent infections.
In 95% of the patients with cold sores, the blisters
occur at the outer edge of the lips which is called
the ‘‘vermilion border.’’ Less often, blisters form on
the nose, chin, or cheek. Following the prodrome, the
GALE ENCYCLOPEDIA OF MEDICINE

Oral herpes may resemble a bacterial infection
called impetigo. This skin infection is most commonly
seen in children and causes herpes-like blisters around
the mouth and nose. Also, because oral herpes can
occur inside the mouth, the blisters could be mistaken
for common canker sores. Therefore, the doctor
would need to determine whether the blisters are oral
herpes, canker sores, or impetigo. The diagnosis and
treatment of herpes infections should be covered by
most insurance providers.
A close-up view of a patient’s mouth with gingivostomatitis
cold sores. (Custom Medical Stock Photo. Reproduced by
permission.)

disease process is rapid. First, small red bumps appear
that quickly form fluid-filled blisters. The painful blisters may either burst and form a scab or dry up and
form a scab. Within two days of the first red bumps, all
the blisters have formed scabs. The skin heals completely and without scarring within six to ten days.
Some children have a very serious primary (first
episode) herpes infection called ‘‘gingivostomatitis.’’
This causes fever, swollen lymph glands, and numerous blisters inside the mouth and on the lips and
tongue that may form large, open sores. These painful
sores may last up to three weeks and can make eating
and drinking difficult. Because of this, young children
with gingivostomatitis are at risk for dehydration
(excessive loss of water from the body).
Most people experience fewer than two recurrent
outbreaks of cold sores each year. Some people never
experience outbreaks, while some have very frequent
outbreaks. In most people, the blisters form in the
same area each time and are triggered by the same
factors (such as stress, sun exposure, etc).

Diagnosis
Because oral herpes is so common, it is diagnosed
primarily by symptoms. It can be diagnosed and
treated by the family doctor, dermatologists (doctors
who specialize in skin diseases) and infectious disease
specialists. Laboratory tests may be performed to
look for the virus. Because healing sores do not
shed much virus, a sample from an open sore would
be taken for viral culture. A sterile cotton swab would
be wiped over open sores and the sample used to
infect human cells in culture. Cells that are killed by
the herpes virus have a certain appearance under
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
There is no cure for herpes virus infections. There
are antiviral drugs available that have some effect on
lessening the symptoms and decreasing the length of
herpes outbreaks. There is evidence that some may
also prevent future outbreaks. These antiviral drugs
work by interfering with the replication of the viruses,
and are most effective when taken as early in the
infection process as possible. For the best results,
drug treatment should begin during the prodrome
stage before blisters are visible. Depending on the
length of the outbreak, drug treatment could continue
for up to 10 days.
Acyclovir (Zovirax) is the drug of choice for herpes
infection and can be given intravenously or taken by
mouth. It can be applied directly to sores as an ointment, but is not very useful in this form. A liquid form
for children is also available. Acyclovir is effective in
treating both the primary infection and recurrent outbreaks. When taken by mouth to prevent an outbreak,
acyclovir reduces the frequency of herpes outbreaks.
During an outbreak of cold sores, salty foods,
citrus foods (oranges etc.), and other foods that irritate the sores should be avoided. Wash the sores once
or twice a day with warm, soapy water and pat gently
to dry. Over-the-counter lip products that contain the
chemical phenol (such as Blistex Medicated Lip
Ointment) and numbing ointments (Anbesol) help to
relieve cold sores. A bandage may be placed over the
sores to protect them and prevent spreading the virus
to other sites on the lips or face. Acetaminophen
(Tylenol) or ibuprofen (Motrin, Advil) may be taken
if necessary to reduce pain and fever.

Alternative treatment
Vitamin and mineral supplements and diet may
have an effect on the recurrence and duration of
cold sores. In general, cold sore sufferers should eat a
931

Cold sore

microscopic examination. The results of this test are
available within two to 10 days.

Cold sore

KEY TERMS
Latent—A nonactive virus which is in a dormant
state within a cell. The herpes virus is latent in the
nervous system.
Prodrome—Symptoms that warn of the beginning
of disease. The herpes prodrome consists of pain,
burning, tingling, or itching at a site before blisters
are visible.
Recurrence—The return of an active infection following a period of latency.

healthy diet of unprocessed foods such as vegetables,
fruits, and whole grains. Alcohol, caffeine, and sugar
should be avoided.
An imbalance in the amino acids lysine and arginine is thought to be one contributing factor in herpes
virus outbreaks. A diet that is rich in the amino acid
lysine may help prevent recurrences of cold sores.
Foods which contain high levels of lysine include most
vegetables, legumes, fish, turkey, and chicken. In one
study, patients taking lysine supplements had milder
symptoms during an outbreak, a shorter healing time,
and had fewer outbreaks than patients who did not take
lysine. Patients should take 1,000 mg of lysine three
times a day during a cold sore outbreak and 500 mg
daily on an ongoing basis to prevent recurrences. Intake
of the amino acid arginine should be reduced. Foods
rich in arginine that should be avoided are chocolate,
peanuts, almonds, and other nuts and seeds.
Vitamin C and bioflavonoids (a substance in fruits
that helps the body to absorb and use vitamin C) have
been shown to reduce the duration of a cold sore outbreak and reduce the number of sores. The vitamin B
complex includes important vitamins that support the
nervous system where viruses can hide out. B complex
vitamins can also help manage stress, an important
contributing factor to the outbreak of herpes viruses.
Applying the oil in vitamin E capsules directly to cold
sores may provide relief. Zinc lozenges appear to affect
the reproduction of viruses and also enhance the
immune system. Ointments containing lemon balm
(Melissa officinalis) or licorice (Glycyrrhiza glabra)
and peppermint (Mentha piperita) have been shown
to help cold sores heal.

herpes, but outbreaks usually occur less frequently
after age 35. The spread of the herpes virus to the eyes
is very serious. The herpes virus can infect the cells in
the cornea and cause scarring that may impair vision.

Prevention
The only way to prevent oral herpes is to avoid
contact with infected persons. This is not an easy
solution because many people are not aware that they
are infected and can easily infect others. Currently there
are no herpes vaccines available, although herpes
vaccines are being tested.
Several practices can reduce the occurrence of
cold sores and the spread of virus to other body locations or people. These practices are:


Avoidance of sun exposure to the face. Before getting
prolonged exposure to the sun, apply sunscreen to
the face and especially to the lips. Wearing a hat with
a large brim is also helpful.



Avoid touching cold sores. Squeezing, picking, or
pinching blisters can allow the virus to spread to
other parts of the lips or face and infect those sites.



Wash hands frequently. Persons with oral herpes
should wash their hands carefully before touching
others. An infected person can spread the virus to
others even when he or she has no obvious blisters.



Avoid contact with others during active infection.
Infected persons should avoid kissing or sexual contact with others until after the cold sores have healed.



Wear gloves when applying ointment to a child’s
sore.



Be especially careful with infants. Never kiss the eyes
or lips of a baby who is under six months old.



Be watchful of infected children. Do not allow
infected children to share toys that may be put into
the mouth. Toys that have been mouthed should be
disinfected before other children play with them.



Maintain good general health. A healthy diet, plenty
of sleep, and exercise help to minimize the chance of
getting a cold or the flu, which are known to bring on
cold sores. Also, good general health keeps the
immune system strong; this helps to keep the virus
in check and prevents outbreaks.

Resources
OTHER

Prognosis
Oral herpes can be painful and embarrassing but, it
is not a serious infection. There is no cure for oral
932

Mayo Clinic Online. March 5, 1998. <http://
www.mayohealth.org>.

Belinda Rowland, PhD
GALE ENCYCLOPEDIA OF MEDICINE

movement can end an attack. Most babies who have
colic do not seem to be in pain between attacks.

Colds see Common cold

Diagnosis
Pediatricians and family physicians suspect colic
in an infant who:

I Colic
Definition
Colic is persistent, unexplained crying in a healthy
baby between two weeks and five months of age.

Description
Colic, which is not a disease, affects 10–20% of all
infants. It is more common in boys than in girls and
most common in a family’s first child. Symptoms of
colic usually appear when a baby is 14–21 days old,
reach a crescendo at the age of three months, and
disappear within the next eight weeks. Episodes
occur frequently but intermittently and usually begin
with prolonged periods of crying in the late afternoon
or evening. They can last for just a few minutes or
continue for several hours. Some babies who have
colic are simply fussy. Others cry so hard that their
faces turn red, then pale.

Causes and symptoms
No one knows what causes colic. The condition
may be the result of swallowing large amounts of air,
which becomes trapped in the digestive tract and
causes bloating and severe abdominal pain.
Other possible causes of colic include:


digestive tract immaturity



food intolerances



hunger or overfeeding



lack of sleep



loneliness



overheated milk or formula



overstimulation resulting from noise, light, or activity



tension

During a colicky episode, babies’ bellies often
look swollen, feel hard, and make a rumbling sound.
Crying intensifies, tapers off, then gets louder. Many
babies grow rigid, clench their fists, curl their toes, and
draw their legs toward their body. A burp or a bowel
GALE ENCYCLOPEDIA OF MEDICINE



has cried loudly for at least three hours a day at least
three times a week for three weeks or longer



is not hungry but cries for several hours between
dinnertime and midnight



demonstrates the clenched fists, rigidity, and other
physical traits associated with colic

The baby’s medical history and a parent’s description of eating, sleeping, and crying patterns are used to
confirm a diagnosis of colic. Physical examination and
laboratory tests are used to rule out infection, intestinal blockage, and other conditions that can cause
abdominal pain and other colic-like symptoms.

Treatment
Medications do not cure colic. Doctors sometimes
recommend simethicone (Mylicon Drops) to relieve
gas pain, but generally advise parents to take a practical approach to the problem.
Gently massaging the baby’s back can release a
trapped gas bubble, and holding the baby in a sitting
position can help prevent air from being swallowed
during feedings. Bottle-fed babies can swallow air if
nipple holes are either too large or too small.
Nipple-hole size can be checked by filling a bottle
with cold formula, turning it upside down, and counting the number of drops released when it is shaken or
squeezed. A nipple hole that is the right size will release
about one drop of formula every second.
Babies should not be fed every time they cry, but
feeding and burping a baby more often may alleviate
symptoms of colic. A bottle-fed baby should be
burped after every ounce, and a baby who is breastfeeding should be burped every five minutes.
When cow’s milk is the source of the symptoms,
bottle-fed babies should be switched to a soy milk
hydrolyzed protein formula. A woman whose baby is
breastfeeding should eliminate dairy products from
her diet for seven days, then gradually reintroduce
them unless the baby’s symptoms reappear.
Since intolerance to foods other than cow’s milk
may also lead to symptoms of colic, breastfeeding
women may also relieve their babies’ colic by eliminating from their diet:
933

Colic

Cold spot myocardial imaging see Thallium
heart scan

Colon cancer



coffee



tea



cocoa



citrus



peanuts



wheat



broccoli and other vegetables belonging to the cabbage family

Rocking a baby in a quiet, darkened room can
prevent overstimulation, and a baby usually calms
down when cuddled in a warm, soft blanket.
Colicky babies cry less when they are soothed by
the motion of a wind-up swing, a car ride, or being
carried in a parent’s arms. Pacifiers can soothe babies
who are upset, but a pacifier should never be attached
to a string.
A doctor should be notified if a baby who has
been diagnosed with colic:

Prevention
Many doctors believe that colic cannot be prevented. Some alternative practitioners, however, feel
that colic can be prevented by an awareness of food
intolerances and their impact.
Resources
ORGANIZATIONS

American Academy of Family Physicians. 8880 Ward
Parkway, Kansas City, MO 64114. (816) 333-9700.
<http://www.aafp.org>.
American Academy of Pediatrics. 141 Northwest Point
Boulevard, Elk Grove Village, IL 60007-1098. (847)
434-4000. <http://www.aap.org>.

Maureen Haggerty

Collapsed lung see Pneumothorax
Colloidal bath see Therapeutic baths



develops a rectal fever higher than 101  F (38.3  C)



cries for more than four hours



vomits

I Colon cancer



has diarrhea or stools that are black or bloody

Definition



loses weight



eats less than normal

Alternative treatment
Applying gentle pressure to the webbed area
between the thumb and index finger of either hand
can calm a crying child. So can gently massaging the
area directly above the child’s navel and the corresponding spot on the spine. Applying warm compresses or holding your hand firmly over the child’s
abdomen can relieve cramping.
Teas made with chamomile (Matricaria recutita),
lemon balm (Melissa officinalis), peppermint (Mentha
piperita), or dill (Anethum graveolens) can lessen bowel
inflammation and reduce gas. A homeopathic combination called ‘‘colic’’ may be effective, and constitutional homeopathic treatment can help strengthen the
child’s entire constitution.

Prognosis
Colic is distressing, but it is not dangerous.
Symptoms almost always disappear before a child is
six months old.
934

Cancer of the colon is the disease characterized by
the development of malignant cells in the lining or
epithelium of the first and longest portion of the
large intestine. Malignant cells have lost normal control mechanisms governing growth. These cells may
invade surrounding local tissue, or they may spread
throughout the body and invade other organ systems.
Synonyms for the colon include the large bowel or
the large intestine. The rectum is the continuation of
the large intestine into the pelvis that terminates in the
anus.

Description
The colon is a tubular organ beginning in the right
lower abdomen. It ascends on the right side of the
abdomen, traverses from right to left in the upper
abdomen, descends vertically down the left side,
takes an S-shaped curve in the lower left abdomen,
and then flows into the rectum as it leaves the abdomen for the pelvis. These portions of the colon are
named separately though they are part of the same
organ:


cecum, the beginning of the colon



ascending colon, the right vertical ascent of the colon
GALE ENCYCLOPEDIA OF MEDICINE

transverse colon, the portion traversing from right
to left



descending colon, the left vertical descent of the
colon



sigmoid colon, the s-shaped segment of colon above
the pelvis

These portions of the colon are recognized anatomically based on the arterial blood supply and venous
and lymphatic drainage of these segments of the colon.
Lymph, a protein-rich fluid that bathes the cells of the
body, is transported in small channels known as lymphatics that run alongside the veins of the colon.
Lymph nodes are small filters through which the
lymph travels on its way back to the bloodstream.
Cancer can spread elsewhere in the body by invading
the lymph and vascular systems. Therefore, these anatomic considerations become very important in the
treatment of colon cancer.

identified clinically is later in the progression than
would be desired and screening becomes a very important endeavor to aid in earlier detection of this disease.
There are at least 100,000 cases of colon cancer
diagnosed per year in the United States. Together,
colon and rectal cancers account for 10% of cancers
in men and 11% of cancers in women. It is the second
most common site-specific cancer affecting both men
and women. A 2003 study reported that for unknown
reasons, women are more likely to have advanced
colon cancer at diagnosis than men. Nearly 57,000
people died from colon and rectal cancer in the
United States in 2003. In recent years the incidence
of this disease has decreased slightly, as has the mortality rate. It is difficult to tell if the decrease in mortality reflects earlier diagnosis, less death related to the
actual treatment of the disease, or a combination of
both factors.

The small intestine is the continuation of the
upper gastrointestinal tract that is responsible for carrying ingested nutrients into the body. The waste left
after the small intestine has finished absorbing nutrients amounts to a few liters (about the same as quart)
of material per day and is directly delivered to the
colon (at the cecum) for processing. The colon is
responsible for the preservation of fluid and electrolytes as it propels the increasingly solid waste toward
the rectum and anus for excretion.

Cancer of the colon is thought to arise sporadically in about 80% of those who develop the disease.
Twenty percent of people are thought to have genetic
predisposition, meaning their genes carry a trigger for
the disease. Development of colon cancer at an early
age, or at multiple sites, or recurrent colon cancer,
suggests a genetically transmitted form of the disease
as opposed to the sporadic form.

When cells lining the colon become malignant, they
first grow locally and may invade partially or totally
through the wall of the bowel and even into adjacent
structures and organs. In the process, the tumor can
penetrate and invade the lymphatics or the capillaries
locally and gain access to the circulation. As the malignant cells work their way to other areas of the body,
they again become locally invasive in the new area to
which they have spread. These tumor deposits, originating in the colon primary tumor, are then known as
metastases. If metastases are found in the regional
lymph nodes from the primary, they are known as
regional metastases or regional nodal metastases. If
they are distant from the primary tumor, they are
known as distant metastases. The patient with distant
metastases has systemic disease. Thus, the cancer originating in the colon begins locally and, given time, can
become systemic.

Causes of colon cancer often are environmental
in sporadic cases (80%) and sometimes genetic
(20%). Since malignant cells have a changed genetic
makeup, this means that in 80% of cases, the environment spontaneously induces change, whereas
those born with a genetic predisposition are either
destined to get the cancer or less environmental exposure can induce the cancer. Exposure to agents in the
environment that may induce mutation is the process
of carcinogenesis and is caused by agents known as
carcinogens (cancer-causing agents). Specific carcinogens have been difficult to identify; however, dietary factors seem to be involved.

By the time the primary is originally detected, it is
usually larger than 0.4 in (1 cm) in size and has over
one million cells. This amount of growth itself is estimated to take about three to seven years. Each time
the cells double in number, the size of the tumor
quadruples. Thus, like most cancers, the part that is
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms

Colon cancer is more common in industrialized
nations. Diets high in fat, red meat, total calories, and
alcohol seem to predispose people to the disease. Diets
high in fiber seem to decrease risk. High-fiber diets
may help lessen exposure of the colon lining to carcinogens from the environment, as the transit time
through the bowel is faster with a high-fiber diet than
it is with a low-fiber diet.
Age plays a definite role in the predisposition to
colon cancer. Two-thirds of all cases occur after age
935

Colon cancer



Colon cancer

50 and the average age for those who develop the
disease is 62.
There also is a slight increased risk for colon
cancer in the individual who smokes.
Patients who suffer from inflammatory diseases of
the colon known as ulcerative colitis and Crohn’s colitis are also at increased risk.
Researchers know there is a genetic link to many
cases of colon cancer, those called familial cases. This
is the type of colon cancer that tends to run in families.
In late 2003, a team of researchers identified the specific location on a human chromosome by analyzing
blood samples from 53 families in which at least one
member had a colon cancer or precancerous colon
polyp. At least 200 genes exist on the location of
chromosome 9, however, so the research will continue
to identify the particular gene responsible for the
cancer.
The development of polyps of the colon usually
precedes the development of colon cancer by five or
more years. Polyps are benign growths of the colon
lining. They can be unrelated to cancer, precancerous,
or malignant. Polyps, when identified, are removed for
diagnosis. If the polyps are benign, the patient should
undergo careful surveillance for the development of
more polyps or the development of colon cancer.
Colon cancer causes symptoms related to its local
presence in the large bowel or by its effect on other
organs if it has spread. These symptoms may occur
alone or in combination:


a change in bowel habit



blood in the stool



bloating, persistent abdominal distention



constipation



a feeling of fullness even after having a bowel
movement



narrowing of the stool—so-called ribbon stools



persistent, chronic fatigue



abdominal discomfort



unexplained weight loss



very rarely, nausea and vomiting

Most of these symptoms are caused by the physical presence of the tumor mass in the colon. Similar
symptoms can be caused by other processes; these are
not absolutely specific to colon cancer. The key is
recognizing that the persistence of these types of symptoms without ready explanation should prompt the
individual to seek medical evaluation.
936

If a tumor develops in the colon, it will begin to
cause symptoms as it reaches a certain size. The symptoms are caused by the tumor blocking the opening in
the colon. In addition, the tumor commonly oozes
blood that is lost in the stool. (Often, this blood is
not visible.) This results in anemia and chronic fatigue.
Weight loss is a late symptom, often implying substantial obstruction or the presence of systemic disease.

Diagnosis
Screening
In all other cancers (breast and prostate, for
example), screening tests look for small, malignant
lesions. Screening for colorectal cancers, however, is
the search for pre-malignant, benign polyps. This
screening can be close to 100% effective in preventing
cancer development, not just in detecting small
cancers.
Screening involves physical exam, simple laboratory tests, and the visualization of the lining of the
colon. To visualize the colon epithelium, clinicians use
x rays (indirect visualization) and endoscopy (direct
visualization).
The physical examination involves the performance
of a digital rectal exam (DRE). The DRE includes
manual examination of the rectum, anus, and the prostate. During this examination, the physician examines
the anus and the surrounding skin for hemorrhoids,
abscesses, and other irregularities. After lubricating
the gloved finger and anus, the examiner gently slides
the finger into the anus and follows the contours of the
rectum. The examiner notes the tone of the anus and
feels the walls and the edges for texture, tenderness and
masses as far as the examining finger can reach. At the
time of this exam, the physician checks the stool on the
examining glove with a chemical to see if any occult
(invisible) blood is present. At home, after having a
bowel movement, the patient is asked to swipe a sample
of stool obtained with a small stick on a card. After
three such specimens are on the card, the card is then
easily chemically tested for occult blood also. (The stool
analysis mentioned here is known as a fecal occult blood
test, or FOBT, and, while it can be helpful, it is not
100% accurate—only about 50% of cancers are FOBTpositive.) These exams are accomplished as an easy part
of a routine yearly physical exam.
Proteins are sometimes produced by cancers, and
these may be elevated in the patient’s blood. When this
occurs, the protein produced is known as a tumor
marker. There is a tumor marker for some cancers of
the colon; it is known as carcinoembryonic antigen, or
GALE ENCYCLOPEDIA OF MEDICINE

Unlike the indirect visualizations of the colon (the
BE and the DCBE), the endoscopic screenings allow
the physician to remove polyps and biopsy suspicious
tissue. (A biopsy is a removal of tissue for examination
by a pathologist.) For this reason, many physicians
prefer endoscopic screening. All of the visualizations,
the BE, DCBE, and each type of endoscopy, require
pre-procedure preparation (evacuation) of the colon.
The American Cancer Society has recommended
the following screening protocol for those at normal
risk over 50 years of age:
A colon with a cancerous growth. (Illustration by Argosy Inc.)

CEA. Unfortunately, this protein may be made by
other adenocarcinomas as well, or it may not be produced by a particular colon cancer. Therefore, screening by chemical analysis for CEA has not been helpful.
CEA has been helpful when used in a follow-up role
for patients treated for colon cancer if their tumor
makes the protein.
Indirect visualization of the colon may be accomplished by placing barium through the rectum and
filling the colon with this compound. Barium produces
a white contrast image of the lining of the colon on x
ray and thus, the contour of the lining of the colon
may be seen. Detail can be increased if the barium
utilized is thinned and air also introduced. These studies are known as the barium enema (BE) and the
double contrast barium enema (DCBE).
Direct visualization of the colon lining is accomplished using a scope or endoscope. The physician
introduces the instrument through the rectum. Older,
shorter scopes were rigid. Today, utilizing fiberoptic
technology, the scopes are flexible and can reach much
farther. If the left colon only is visualized, it is called
flexible sigmoidoscopy. When the entire colon is visualized, the procedure is known as colonoscopy
A procedure called virtual colonoscopy has been
developed but debate continues on whether or not it is
effective as colonoscopy. Virtual colonoscopy refers to
the use of imaging, usually with computed tomography
(CT) scans or magnetic resonance imaging (MRI)
to produce images of the colon. Studies in late 2003
showed that virtual colonoscopy was as effective as
colonoscopy for screening purposes and it offered the
GALE ENCYCLOPEDIA OF MEDICINE



yearly fecal occult blood test



flexible sigmoidoscopy at age 50



flexible sigmoidoscopy repeated every five years



double contrast barium enema every five years



colonoscopy every 10 years

The American Gastroenterologial Association
revised its screening guidelines in 2003 to recommend
that people with two or more first-degree relatives
with colorectal cancer or a first-degree relative with
colon or rectal cancer before age 60 should have a
screening colonoscopy beginning at age 40 or beginning 10 years prior to the age of the earlier colon
cancer diagnosis in their family (whichever is earliest).
Those with a first-degree relative diagnosed with colon
cancer after age 60 or two second-degree relative with
colon or rectal cancer should begin screening at age 40
with one of the methods listed above, such as annual
sigmoidoscopy.
Evaluation of patients with symptoms
If patients have symptoms that could possibly be
related to colon cancer, the entire colon will be examined. The combination of a flexible sigmoidoscopy
and DCBE may be performed, but the preferred evaluation of the entire colon and rectum is a complete
colonoscopy. Colonoscopy allows direct visualization,
photography, and the opportunity to obtain a biopsy
of any abnormality visualized. If, for technical reasons, the entire colon is not visualized endoscopically,
a DCBE should complement the colonoscopy.
The diagnosis of colon cancer is actually made by
the performance of a biopsy of any abnormal lesion in
the colon. When a tumor growth is identified, it could
937

Colon cancer

advantage of being less invasive and less risky.
However, many physicians were unwilling to accept
it as a replacement for colonoscopy, particularly since
some patients might still require the regular colonoscopy as a follow-up to the virtual procedure if a polyp
or abnormality is found that requires biopsy.

Colon cancer

be either a benign polyp (or lesion) or a cancer; the
biopsy resolves the issue. The endoscopist may take
many samples to exclude any sampling errors.
If the patient has advanced disease at the time of
diagnosis, areas where the tumor has spread (such as
the liver) may be amenable to biopsy. Such biopsies
are usually obtained using a special needle under local
anesthesia.
Once a diagnosis of colon cancer has been established by biopsy, in addition to the physical exam,
studies will be performed to assess the extent of the
disease. Blood studies include a complete blood count,
liver function tests, and a CEA. Imaging studies will
include a chest x ray and a CAT scan (computed tomography scan) of the abdomen. The chest x ray will
determine if the cancer has is spread to the lung, and
the CAT scan will evaluate potential spread to the liver
as well as any local spread of the primary tumor. If the
patient has neurological symptoms, a CAT scan of the
brain will be performed, and if the patient is experiencing bone pain, a bone scan also will be performed.

Treatment
Once the diagnosis has been confirmed by biopsy,
the clinical stage of the cancer is assigned. Using the
characteristics of the primary tumor, its depth of penetration through the bowel, and the presence or absence
of regional or distant metastases, the stage of the
cancer is derived. Often, the depth of penetration
through the bowel or the presence of regional lymph
nodes cannot be assigned before surgery.
Colon cancer is assigned stages I through IV based
on the following general criteria:


Stage I: the tumor is confined to the epithelium or
has not penetrated through the first layer of muscle
in the bowel wall.



Stage II: the tumor has penetrated through to the
outer wall of the colon or has gone through it, possibly invading other local tissue.



Stage III: any depth or size of tumor associated with
regional lymph node involvement.



Stage IV: any of previous criteria associated with
distant metastasis.

With many cancers other than colon cancer, staging plays an important pre-treatment role to best
determine treatment options. Almost all colon cancers
are treated with surgery first, regardless of stage.
Colon cancers through stage III, and even some
stage IV colon cancers, are treated with surgery first
before any other treatments are considered.
938

Surgery
Surgical removal of the involved segment of colon
(colectomy) along with its blood supply and regional
lymph nodes is the primary therapy for colon cancer.
Usually, the partial colectomies are separated into
right, left, transverse, or sigmoid sections based on
the blood supply. The removal of the blood supply at
its origin along with the regional lymph nodes that
accompany it ensures an adequate margin of normal
colon on either side of the primary tumor. When the
cancer lies in a position such that the blood supply and
lymph drainage between two of the major vessels, both
vessels are taken to assure complete radical resection
or removal (extended radical right or left colectomy).
If the primary tumor penetrates through the bowel
wall, any tissue adjacent to the tumor extension is
also taken if feasible.
Surgery is used as primary therapy for stages I
through III colon cancer unless there are signs that
local invasion will not permit complete removal of the
tumor, as may occur in advanced stage III tumors.
However, this circumstance is rare, occurring in less
than 2% of all colon cancer cases.
After the resection is completed, the ends of the
remaining colon are reconstructed; the hook-up is
called an anastomosis. Once healing has occurred,
there may be a slight increase in the frequency of
bowel movements. This effect usually lasts only for
several weeks. Most patients go on to develop completely normal bowel function.
Occasionally, the anastomosis is risky and cannot
be performed. When the anastomosis cannot be performed, a colostomy is performed instead. A colostomy is performed by bringing the end of the colon
through the abdominal wall and sewing it to the skin.
The patient will have to wear an appliance (a bag) to
manage the stool. The colostomy may be temporary
and the patient may undergo a hook-up at a later,
safer date, or the colostomy may be permanent. In
most cases, emergent colostomies are not reversed
and are permanent.
Radiation
Radiation therapy is used as an adjunct to surgery
if there is concern about potential for local recurrence
post-operatively and the area of concern will tolerate
the radiation. For instance, if the tumor invaded muscle of the abdominal wall but was not completely
removed, this area would be considered for radiation.
Radiation has significant dose limits when residual
bowel is exposed to it because the small and large
intestine do not tolerate radiation well.
GALE ENCYCLOPEDIA OF MEDICINE

Chemotherapy
Chemotherapy is useful for patients who have had
all identifiable tumor removed and are at risk for recurrence (adjuvant chemotherapy). Chemotherapy may
also be used when the cancer is stage IV and is beyond
the scope of regional therapy, but this use is rare.
Adjuvant therapy is considered in stage II disease
with deep penetration or in stage III patients.
Standard therapy is treatment with 5-fluorouracil,
(5FU) combined with leucovorin for a period of six
to 12 months. 5FU is an antimetabolite, and leucovorin improves the response rate. (A response is a temporary regression of the cancer from chemotherapy.)
Another agent, levamisole, (which seems to stimulate
the immune system), may be substituted for leucovorin. These protocols reduce rate of recurrence by
about 15% and reduce mortality by about 10%. The
regimens do have some toxicity, but usually are tolerated fairly well.
Similar chemotherapy may be administered for
stage IV disease or if a patient progresses and develops
metastases. Results show response rates of about
20%. Unfortunately, these patients eventually succumb to the disease, and this chemotherapy may not
prolong survival or improve quality of life in Stage IV
patients. Clinical trials have now shown that the
results can be improved with the addition of another
agent to this regimen. Irinotecan does not seem to
increase toxicity but it improved response rates to
39%, added two to three months to disease-free survival, and prolonged overall survival by a little over two
months.

Alternative treatment
Alternative therapies have not been studied in a
large-scale, scientific way. Large doses of vitamins,
fiber, and green tea are among therapies tried.
Avoiding cigarettes and alcohol may be helpful.
Before initiating any alternative therapies, the patient
is wise to consult his or her physician to be sure that
these therapies do not complicate or interfere with the
established therapy.

Prognosis
Prognosis is the long-term outlook or survival
after therapy. Overall, about 50% of patients treated
for colon cancer survive the disease. As expected, the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Adenocarcinoma—Type of cancer beginning in
glandular epithelium.
Adjuvant therapy—Treatment involving radiation,
chemotherapy (drug treatment), or hormone therapy, or a combination of all three given after the
primary treatment for the possibility of residual
microscopic disease.
Anastomosis—Surgical reconnection of the ends of
the bowel after removal of a portion of the bowel.
Anemia—The condition caused by too few circulating red blood cells, often manifested in part by
fatigue.
Carcinogens—Substances in the environment that
cause cancer, presumably by inducing mutations,
with prolonged exposure.
Electrolytes—Salts, such as sodium and chloride.
Epithelium—Cells composing the lining of an organ.
Lymphatics—Channels that are conduits for lymph.
Lymph nodes—Cellular filters through which lymphatics flow.
Malignant—Cells that have been altered such that
they have lost normal control mechanisms and are
capable of local invasion and spread to other areas
of the body.
Metastasis—Site of invasive tumor growth that originated from a malignancy elsewhere in the body.
Mutation—A change in the genetic makeup of a
cell that may occur spontaneously or be environmentally induced.
Occult blood—Presence of blood that cannot be
seen with the naked eye.
Polyps—Localized growths of the epithelium that
can be benign, precancerous, or harbor malignancy.
Radical resection—Surgical resection that takes
the blood supply and lymph system supplying the
organ along with the organ.
Resect—To remove surgically.
Sacrum—Posterior bony wall of the pelvis.
Systemic—Referring to throughout the body.

survival rates are dependent upon the stage of the
cancer at the time of diagnosis, making early detection
crucial. If the cancer is detected early, surgical removal
of the tumor can lead to complete cure in 75%–90% of
patients.
939

Colon cancer

Radiation also is used in the treatment of patients
with metastatic disease. It is particularly useful in
shrinking metastatic colon cancer to the brain.

Colonic irrigation

About 15% of patients present with stage I disease
and 85–90% survive. Stage II represents 20–30% of
cases and 65–75% survive. Thirty to forty percent
comprise the stage III presentation of which 55%
survive. The remaining 20–25% present with stage
IV disease and are rarely cured.

Prevention
There is not an absolute method for preventing
colon cancer. Still, there are steps an individual can
take to dramatically lessen the risk or to identify the
precursors of colon cancer so that it does not manifest
itself. High-fiber diets and vitamins, avoiding obesity,
and staying active lessen the risk. Avoiding cigarettes
and alcohol may be helpful. By controlling these environmental factors, an individual can lessen risk and to
this degree prevent the disease.
People who turn age 50, and all of those with a
history of colon cancer in their families, should speak
with their physicians about the most recent screening
recommendations from physician and cancer organizations. They should watch for symptoms and attend
all recommended screenings to increase the likelihood
of catching colon cancer early.

‘‘Study Shows Virtual Colonoscopy as Effective as Traditional
Colonoscopy.’’ Biotech Week December 31, 2003.
Wachter, Kerri. ‘‘Reasons Unclear for Later Colon Cancer
Diagnosis in Women: Regional or Distant Disease More
Likely.’’ Internal Medicine News 36 ( December 1, 2003).
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800)ACS-2345. <http://www.cancer.org>.
Cancer Information Service of the NCI. 9000 Rockville Pike,
Building 31, Suite 10A18, Bethesda, MD 20892. 1-8004-CANCER. <http://wwwicic.nci.nih.gov>.
Colon Cancer Alliance. <http://www.ccalliance.org>.
National Cancer Institute Cancer Trials.
<http://cancertrials.nci.nih.gov/system>.
<http://www.cancertrials.com>.

Richard A. McCartney, M.D.
Teresa G. Odle

Colon therapy see Colonic irrigation

I Colonic irrigation
Definition

Resources
BOOKS

Abelhoff, Martin, James O. Armitage, Allen S. Lichter, and
John E. Niederhuber. Clinical Oncology Library.
Philadelphia: Churchill Livingstone, 1999.
Jorde, Lynn B., John C. Carey, Michael J. Bamshad, and
Raymond L. White. Medical Genetics. 2nd ed.
St. Louis: Mosby, 1999.
PERIODICALS

‘‘Colon Cancer; Facts to Know.’’ NWHRC Health Center
December 15, 2003.
Golden, William E., and Robert H. Hopkins. ‘‘Colon
Cancer Screening 2003.’’ Internal Medicine News 36
(December 1, 2003): 46.
Greenlee, Robert T., MPH, Mary Beth Hill-Harmon,
Taylor Murray, and Michael Thun. ‘‘Cancer Statistics
2001.’’ CA: A Cancer Journal for Clinicians 51, no. 1
(January-February 2001).
‘‘Professional Organization Recommends Standard
Colonoscopy Over Virtual.’’ Biotech Week December
31, 2003: 422.
‘‘Researchers Discover New Genetic Link to Common
Colon Cancer.’’ Genomics & Genetics Weekly
November 7, 2003: 29.
Saltz, Leonard, et al. ‘‘Irinotecan plus Fluorouracil and
Leucovorin for Metastatic Colorectal Cancer.’’ The
New England Journal of Medicine 343, no. 13
(September 28, 2000).
940

Colonic irrigation is also known as hydrotherapy
of the colon, high colonic, entero-lavage, or simply
colonic. It is the process of cleansing the colon by
passing several gallons of water through it with the
use of special equipment. It is similar to an enema but
treats the whole colon, not just the lower bowel. This
has the effect of flushing out impacted fecal matter,
toxins, mucous, and even parasites, that often build up
over the passage of time. It is a procedure that should
only be undertaken by a qualified practitioner.

Purpose
Anyone suffering from gas, bloating, cramping
pains, acne and other skin complaints, arthritis, and a
list of bowel complaints such as diverticulitis and irritable bowel etc., may benefit from colonic irrigation. In
particular, cancer patients are often advised to undertake a course of colonic irrigation sessions as an essential part of their treatment. When a biological cancer
therapy begins to enable the body to breakdown a
cancerous mass, it is essential that speedy and effective
elimination of the resulting toxins is achieved.
Colon and bowel cancer is one of the leading
causes of death in the United States, and alternative
practitioners insist that it can be prevented by efficient
hygiene procedures. Providing that care is taken to
GALE ENCYCLOPEDIA OF MEDICINE

Removing large amounts of toxic matter relieves
the patient and can lead to the alleviation of symptoms
such as arthritis, chronic fatigue syndrome, candidiasis,
and a host of other illnesses. Properly executed, colonic irrigation can help restore normal peristaltic action
to a sluggish bowel, thus reducing the need for more
hydrotherapy treatments over time. In addition,
removing the layer of fecal matter which coats the
intestines in many individuals allows improved assimilation of the nutrients from foods and can alleviate
symptoms of vitamin and other nutrient deficiencies.
Many alternative health practitioners consider some
form of hydrotherapy for the bowel to be essential in
the treatment of degenerative diseases.

Description
Origins
Cleansing the colon with the use of hydrotherapy
is not a new concept. Forms of colonic irrigation have
been used successfully for decades to relieve chronic
toxicity and even acute cases of toxemia.
Over time, many people develop a thick layer of
fecal matter that coats their colon. It hardens and
becomes impacted, reducing the efficiency of the
bowel, and in some cases, completely obstructing normal elimination of waste matter from the body. It is
quite common for people to have only one bowel
movement per day, and some as few as one or two
per week.
Alternative practitioners advise that we probably
should have one bowel movement for every meal that
we eat. If not, then we are not eliminating wastes
completely, and if input exceeds output, then we will
surely suffer the consequences at some point.
Incomplete elimination of body wastes may
result in the following, depending on where the
deposits end up:


sluggish system



joint pain and arthritis



irritable bowel syndrome



diverticulitis



Crohn’s disease



leaky gut syndrome

GALE ENCYCLOPEDIA OF MEDICINE



heart problem



migraine



allergies



bad breath



acne and other skin problems such as psoriasis



asthma



early senility and Alzheimer’s disease



chronic fatigue syndrome



cancer, particularly of the bowel



multiple sclerosis

Colonic irrigation

replace the natural organisms that flourish in the
bowel, many health benefits can be expected from
colonic irrigation. In general, alternative practitioners
maintain that an ill-functioning bowel is the source of
all disease, and therefore keeping it clean will be an
effective protection against this.

During colonic irrigation, a small speculum is
passed into the patient’s bowel through the rectum.
This is attached to a tube, which leads to a machine
that pumps temperature-controlled water into the
colon at a controlled rate (to be controlled by either
the practitioner or the patient). The temperature of the
water should ideally be kept as close to body temperature as possible.
The patient will temporarily be filled with water
up to the level of the entire colon. Patients say they can
feel the water up under their ribs but that the process,
although sometimes uncomfortable, is not painful.
The amount of water will vary but will generally be
in the region of between two and six liters (or quarts)
at any one time. This triggers peristaltic action and the
patient will begin to expel the water along with fecal
matter back through the tube and into the machine.
The fecal matter is flushed out through a viewing
tube, so that what is eliminated may be monitored.
Quite often, unsuspected parasites are expelled, along
with very old fecal material, very dark in color, which
may have been in the colon for years. Some therapists
comment that it looks like aging rubber.
During the treatment, the therapist will gently
massage the patient’s abdomen to help dislodge
impacted fecal matter. In addition to massage, sometimes acupressure, reflexology, or lymphatic drainage
techniques may be used to loosen deposits and stimulate the bowel. It is important that the right amount of
water is used, as too much will cause discomfort and
too little will be ineffective. If correctly done, colonic
irrigation is not painful at all and some patients claim
to sleep through their treatment.
Sanitation is vital to this process. The tubes and
speculums used are generally disposable, but other
parts of the machine, such as the viewing tube, must
be sterilized after each patient.
Normally, a series of treatments will be required
to achieve desired results regarding the elimination of
941

Colonoscopy

impacted, decaying matter, and restoration of bowel
regularity. Initially only gas and recent fecal matter
may be expelled. The residue attached to the colon
wall is usually the result of years of neglect, and therapists say that one cannot expect complete relief in only
one session.
Impacted fecal matter can cause an imbalance of
the natural organisms that normally populate the
bowel, causing what is known as dysbiosis. Under
ideal conditions, the bowel is populated by a variety
of naturally occurring organisms. It seems that the
enzymes occurring in fresh fruit and vegetables encourage these beneficial organisms. One of the results of
eating processed denatured foods is that this natural
balance is upset, and food may begin to rot in the
bowel instead of being processed.
Decomposing matter can cause a toxic condition
and may lead to many health problems, as constipation
causes backed up pollution of the body cells. The
process of repair and elimination of wastes enters a
downward spiral which at best will cause fatigue, lack
of energy and premature aging, and, at worst, can
cause degenerative diseases, among them allergies,
and even cancer and Alzheimer’s disease.
The cost of colonic irrigation treatments varies,
but is generally between $35–70 per session, which
may last from 45 minutes to one hour. The cost of
the machine itself ranges from $4,000–12,000, but
again, it should be noted that only qualified therapists
should conduct sessions.

Preparations
Most practitioners prefer that distilled or purified
water is used for colonic irrigation, but others use
sterilized tap water.

Precautions
It may be advisable to use a probiotic pessary after
colonic irrigation, to ensure replacement of desirable
natural flora. There are certain conditions that either
partly or completely preclude the use of colonic irrigation, such as an active attack of Crohn’s disease, bleeding ulcers, and hyperacidosis. If in doubt, a qualified
practitioner should be consulted. Anyone suffering
from these conditions should always notify the practitioner when receiving colonic irrigation treatments.

Side effects
Some allopathic practitioners claim that colonic
irrigation flushes out essential electrolytes and friendly
942

KEY TERMS
Dysbiosis—The condition that results when the
natural flora of the gut are thrown out of balance,
such as when antibiotics are taken.
Peristalsis—The natural wave-like action of a
healthy bowel that transports matter from one end
of the bowel to the other.
Probiotics—Supplements of beneficial microorganisms that normally colonize the gut.
Toxemia—Poisoning of the blood.

bacteria from the bowel and that it can be dangerous.
Practitioners counter that this can easily be remedied
with the use of probiotics, and that in any case, these
possible disadvantages are easily offset by the benefits
of having large amounts of putrefying matter, harmful
organisms, and parasites removed from the system.

Research and general acceptance
Although many alternative health care practitioners swear by colonic irrigation, there is a large allopathic lobby that claims that there are no benefits to be
had, and that there are dangers involved. However,
there are many decades of records and research from
the alternative health care community that indicate that
this therapy may have a valuable place in the treatment
of degenerative diseases and toxic conditions.
Resources
ORGANIZATIONS

California Colon Hygienist Society. 333 Miller Ave., Suite 1,
Mill Valley, CA 94941. (415) 383-7224.
Intestinal Health Institute. 4427 East Fifth St., Tucson, AZ
85711. (520) 325-9686. info@sheilas.com. <http://
www.sheilas.com>.

Patricia Skinner

I Colonoscopy
Definition
Colonoscopy is a medical procedure where a long,
flexible, tubular instrument called the colonoscope is
used to view the entire inner lining of the colon (large
intestine) and the rectum.
GALE ENCYCLOPEDIA OF MEDICINE

A colonoscopy is generally recommended when the
patient complains of rectal bleeding or has a change in
bowel habits and other unexplained abdominal symptoms. The test is frequently used to test for colorectal
cancer, especially when polyps or tumor-like growths
have been detected using the barium enema and other
diagnostic tests. Polyps can be removed through the
colonoscope and samples of tissue (biopsies) can be
taken to test for the presence of cancerous cells.
The test also enables the physician to check for
bowel diseases such as ulcerative colitis and Crohn’s
disease. It is a necessary tool in monitoring patients
who have a past history of polyps or colon cancer.

Description
The procedure can be done either in the doctor’s
office or in a special procedure room of a local hospital. An intravenous (IV) line will be started in a vein in
the arm. The patient is generally given a sedative and a
pain-killer through the IV line.
During the colonoscopy, the patient will be asked
to lie on his/her left side with his/her knees drawn up
towards the abdomen. The doctor begins the procedure by inserting a lubricated, gloved finger into the
anus to check for any abnormal masses or blockage. A
thin, well-lubricated colonoscope then will be inserted
into the anus and it will be gently advanced through
the colon. The lining of the intestine will be examined
through the scope. Occasionally air may be pumped
through the colonoscope to help clear the path or open
the colon. If there are excessive secretions, stool, or
blood that obstruct the viewing, they will be suctioned
out through the scope. The doctor may press on the
abdomen or ask the patient to change his/her position
in order to advance the scope through the colon.
The entire length of the large intestine can be examined in this manner. If suspicious growths are observed,
tiny biopsy forceps or brushes can be inserted through
the colon and tissue samples can be obtained. Small
polyps also can be removed through the colonoscope.
After the procedure, the colonoscope is slowly withdrawn and the instilled air is allowed to escape. The
anal area is then cleansed with tissues.
The procedure may take anywhere from 30 minutes
to two hours depending on how easy it is to advance the
scope through the colon. Colonoscopy can be a long
and uncomfortable procedure, and the bowel cleaning
preparation may be tiring and can produce diarrhea and
cramping. During the colonoscopy, the sedative and the
pain medications will keep the patient very drowsy and
GALE ENCYCLOPEDIA OF MEDICINE

relaxed. Most patients complain of minor discomfort
and pressure from the colonoscope moving inside.
However, the procedure is not painful.
A procedure called virtual colonoscopy has been
developed but debate continues on whether or not it is
effective as colonoscopy. Virtual colonoscopy refers to
the use of imaging, usually with computed tomography
(CT) scans or magnetic resonance imaging (MRI)
to produce images of the colon. Studies in late 2003
showed that virtual colonoscopy was as effective as
colonoscopy for screening purposes and it offered the
advantage of being less invasive and less risky.
However, many physicians were unwilling to accept
it as a replacement for colonoscopy, particularly since
some patients might still require the regular colonoscopy as a follow-up to the virtual procedure if a polyp
or abnormality is found that requires biopsy.

Preparation
The doctor should be notified if the patient has
allergies to any medications or anesthetics; any bleeding problems; or if the woman is pregnant. The doctor
should also be informed of all the medications that the
person is currently on and if he or she has had a
barium x-ray examination recently. If the patient has
had heart valves replaced, the doctor should be
informed so that appropriate antibiotics can be administered to prevent any chance of infection. The risks
of the procedure will be explained to the patient before
performing the procedure and the patient will be asked
to sign a consent form.
It is important that the colon be thoroughly
cleaned before performing the examination. Before
the examination, considerable preparation is necessary to clear the colon of all stool. The patient will be
asked to refrain from eating any solid food for 24–48
hours before the test. Only clear liquids such as juices,
broth, and gelatin are recommended. The patient is
advised to drink plenty of water to avoid dehydration.
The evening before the test, the patient will have to
take a strong laxative that the doctor has prescribed.
Several 1 qt enemas of warm tap water may have to be
taken on the morning of the exam. Commercial enemas (e.g., Fleet) may be used.
The patient will be given specific instructions on
how to use the enema and how many such enemas are
necessary. Generally, the procedure has to be repeated
until the return from the enema is clear of stool particles. On the morning of the examination, the patient is
instructed not to eat or drink anything. The preparatory procedures are extremely important since, if the
colon is not thoroughly clean, the exam cannot be done.
943

Colonoscopy

Purpose

Colonoscopy

Colon

Light
Polyp
Light
Polyp

Viewing monitor
Rectum

Colonoscope

Colonoscopy is a procedure where a long and flexible tubular instrument called a colonoscope is inserted into the patient’s
anus in order to view the lining of the colon and rectum. It is performed to test for colorectal cancer and other bowel diseases,
and enables the physician to collect tissue samples for laboratory analysis. (Illustration by Electronic Illustrators Group.)

Aftercare
After the procedure, the patient is kept under
observation until the effects of the medications wear
off. The patient will have to be driven home by someone and can generally resume a normal diet and usual
activities unless otherwise instructed. The patient will
be advised to drink lots of fluids to replace those lost
by laxatives and fasting.
For a few hours after the procedure, the patient
may feel groggy. There may be some abdominal
cramping and considerable amount of gas may be
passed. If a biopsy was performed or a polyp was
removed, there may be small amounts of blood in the
stool for a few days. If the patient experiences severe
abdominal pain or has persistent and heavy bleeding,
it should be brought to the doctor’s attention
immediately.

Risks
The procedure is virtually free of any complications and risks. Very rarely (two in 1000 cases) there
944

may be a perforation (a hole) in the intestinal wall.
Heavy bleeding due to the removal of the polyp or
from the biopsy site seldom occurs (one in 1000 cases).
Infections due to a colonoscopy are also extremely
rare. Patients with artificial or abnormal heart valves
are usually given antibiotics before and after the procedure to prevent an infection.

Normal results
The results are said to be normal if the lining of the
colon is a pale reddish pink and no abnormal looking
masses are found in the lining of the colon.

Abnormal results
Abnormal results would imply that polyps or
other suspicious-looking masses were detected in the
lining of the intestine. Polyps can be removed during
the procedure and tissue samples can be biopsied. If
cancerous cells are detected in the tissue samples, then
a diagnosis of colon cancer is made. The pathologist
analyzes the tumor cells further to estimate the
GALE ENCYCLOPEDIA OF MEDICINE

Barium enema—An x-ray test of the bowel after
giving the patient an enema of a white chalky substance that outlines the colon and the rectum.
Biopsy—Removal of a tissue sample for examination under the microscope to check for cancer cells.

Cancer Research Institute. 681 Fifth Ave., New York, N.Y.
10022. (800) 992-2623. <http://
www.cancerresearch.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
United Ostomy Association, Inc. (UOA). 19772 MacArthur
Blvd., Suite 200, Irvine, CA 92612-2405. (800)
826-0826. <http://www.uoa.org>.

Colonoscope—A thin, flexible, hollow, lighted
tube that in inserted through the rectum into the
colon to enable the doctor to view the entire lining
of the colon.
Crohn’s disease—A chronic inflammatory disease
where the immune system starts attacking one’s
own body. The disease generally starts in the gastrointestinal tract.
Diverticulosis—A condition where pouchlike sections that bulge through the large intestine’s muscular walls but are not inflamed occur. They may
cause bleeding, stomach distress, and excess gas.
Pathologist—A doctor who specializes in the diagnosis of disease by studying cells and tissues under
a microscope.
Polyps—Abnormal growths that develop on the
inside of a hollow organ such as the colon.
Ulcerative colitis—A chronic condition where
recurrent ulcers are found in the colon. It is manifested clinically by abdominal cramping, and rectal bleeding.

aggressiveness of the tumor and the extent of spread of
the disease. This is crucial before deciding on the mode
of treatment for the disease. Abnormal findings could
also be due to inflammatory bowel diseases such
as ulcerative colitis or Crohn’s disease. A condition
called diverticulosis, where many small fingerlike
pouches protrude from the colon wall, may also contribute to an abnormal result in the colonoscopy.
Resources
PERIODICALS

‘‘Professional Organization Recommends Standard
Colonoscopy Over Virtual.’’ Biotech Week December
31, 2003.
‘‘Study Shows Virtual Colonoscopy as Effective as
Traditional Colonoscopy.’’ Biotech Week Dec. 31, 2003.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Lata Cherath, PhD
Teresa G. Odle

I Color blindness
Definition
Color blindness is an abnormal condition characterized by the inability to clearly distinguish different
colors of the spectrum. The difficulties can be mild to
severe. It is a misleading term because people with
color blindness are not blind. Rather, they tend to
see colors in a limited range of hues; a rare few may
not see colors at all.

Description
Normal color vision requires the use of specialized
receptor cells called cones, which are located in the
retina of the eye. There are three types of cones,
termed red, blue, and green, which enable people to
see a wide spectrum of colors. An abnormality, or
deficiency, of any of the types of cones will result in
abnormal color vision.
There are three basic variants of color blindness.
Red/green color blindness is the most common deficiency, affecting 8% of Caucasian males and 0.5% of
Caucasian females. The prevalence varies with culture.
Blue color blindness is an inability to distinguish
both blue and yellow, which are seen as white or gray.
It is quite rare and has equal prevalence in males and
females. It is common for young children to have blue/
green confusion that becomes less pronounced in
adulthood. Blue color deficiency often appears in people who have physical disorders such as liver disease or
diabetes mellitus.
A total inability to distinguish colors (achromatopsia) is exceedingly rare. These affected individuals
view the world in shades of gray. They frequently have
poor visual acuity and are extremely sensitive to light
945

Color blindness

KEY TERMS

Color blindness

(photophobia), which causes them to squint in ordinary light.
Researchers studying red/green color blindness in
the United Kingdom reported an average prevalence of
only 4.7% in one group. Only 1% of Eskimo males are
color blind. Approximately 2.9% of boys from Saudi
Arabia and 3.7% from India were found to have deficient color vision. Red/green color blindness may
slightly increase an affected person’s chances of contracting leprosy. Pre-term infants exhibit an increased
prevalence of blue color blindness. Achromatopsia has
a prevalence of about 1 in 33,000 in the United States
and affects males and females equally.

sickle cell anemia, and retinitis pigmentosa. Accidents
or strokes that damage the retina or affect particular
areas of the brain eye can lead to color blindness.
Some medications such as antibiotics, barbiturates,
anti-tuberculosis drugs, high blood pressure medications, and several medications used to treat nervous
disorders and psychological problems may cause color
blindness. Industrial or environmental chemicals such
as carbon monoxide, carbon disulfide, fertilizers, styrene, and some containing lead can cause loss of color
vision. Occasionally, changes can occur in the affected
person’s capacity to see colors after age 60.

Diagnosis
Causes and symptoms
Red/green and blue color blindness appear to be
located on at least two different gene locations. The
majority of affected individuals are males. Females are
carriers, but are not normally affected. This indicates
that the X chromosome is one of the locations for
color blindness. Male offspring of females who carry
the altered gene have a 50-50 chance of being colorblind. The rare female that has red/green color blindness, or rarer still, blue color blindness, indicates there
is an involvement of another gene. As of 2001, the
location of this gene has not been identified.
Achromatopsia, the complete inability to distinguish color, is an autosomal recessive disease of the
retina. This means that both parents have one copy of
the altered gene but do not have the disease. Each of
their children has a 25% chance of not having the gene,
a 50% chance of having one altered gene (and, like the
parents, being unaffected), and a 25% risk of having
both the altered gene and the condition. In 1997, the
achromatopsia gene was located on chromosome 2.
The inability to correctly identify colors is the only
sign of color blindness. It is important to note that
people with red/green or blue varieties of color blindness use other cues such as color saturation and object
shape or location to distinguish colors. They can often
distinguish red or green if they can visually compare the
colors. However, most have difficulty accurately identifying colors without any other references. Most people with any impairment in color vision learn colors, as
do other young children. These individuals often reach
adolescence before their visual deficiency is identified.
Color blindness is sometimes acquired. Chronic
illnesses that can lead to color blindness include
Alzheimer’s disease, diabetes mellitus, glaucoma, leukemia, liver disease, chronic alcoholism, macular
degeneration, multiple sclerosis, Parkinson’s disease,
946

There are several tests available to identify problems associated with color vision. The most commonly used is the American Optical/Hardy, Rand,
and Ritter Pseudoisochromatic test. It is composed
of several discs filled with colored dots of different
sizes and colors. A person with normal color vision
looking at a test item sees a number that is clearly
located somewhere in the center of a circle of variously
colored dots. A color-blind person is not able to distinguish the number.
The Ishihara test is comprised of eight plates that
are similar to the American Optical Pseudoisochromatic
test plates. The individual being tested looks for numbers among the various colored dots on each test plate.
Some plates distinguish between red/green and blue
color blindness. Individuals with normal color vision
perceive one number. Those with red/green color deficiency see a different number. Those with blue color
vision see yet a different number.
A third analytical tool is the Titmus II Vision
Tester Color Perception test. The subject looks into a
stereoscopic machine. The test stimulus most often
used in professional offices contains six different
designs or numbers on a black background, framed
in a yellow border. Titmus II can test one eye at a time.
However, its value is limited because it can only identify red/green deficiencies and is not highly accurate.

Treatment
There is no treatment or cure for color blindness.
Most color vision deficient persons compensate well
for their abnormality and usually rely on color cues
and details that are not consciously evident to persons
with typical color vision.
Inherited color blindness cannot be prevented. In
the case of some types of acquired color deficiency, if
the cause of the problem is removed, the condition may
GALE ENCYCLOPEDIA OF MEDICINE

Achromatopsia—The inability to distinguish any
colors.
Cones—Receptor cells that allow the perception of
colors.
Photophobia—An extreme sensitivity to light.
Retina—The light-sensitive layer of tissue in the
back of the eye that receives and transmits visual
signals to the brain through the optic nerve.

‘‘Medical Encyclopedia: Colorblind.’’ MEDLINEplus.
<http://medlineplus.adam.com/ency/article/
001002sym.htm>.
University of Manchester. <http://www.umist.ac.uk/
UMIST_OVS/welcome.html>.
University of Nevada–Reno. <http://www.delamare.unr.
edu/cb/>.

L. Fleming Fallon, Jr., MD, DrPH

Colorectal cancer see Colon cancer; Rectal
cancer

Rod—Photoreceptor that is highly sensitive to low
levels of light and transmits images in shades of gray.

I Colostomy

improve with time. But for most people with acquired
color blindness, the damage is usually permanent.

Prognosis
Color blindness that is inherited is present in both
eyes and remains constant over an individual’s entire
life. Some cases of acquired color vision loss are not
severe, may appear in only one eye, and last for only a
short time. Other cases tend to be progressive, becoming worse with time.
Resources
BOOKS

Wiggs, Janey L. ‘‘Color Vision.’’ In Ophthalmology, edited
by Myron Yanoff and Jay S. Duker. St. Louis: Mosby,
2000.
ORGANIZATIONS

Achromatopsia Network. c/o Frances Futterman, PO Box
214, Berkeley, CA 94701-0214. <http://www.achromat.org/how_to_ join.html>.
American Academy of Ophthalmology. PO Box 7424, San
Francisco, CA 94120-7424. (415) 561-8500. <http://
www.eyenet.org>.
International Colour Vision Society: Forschungsstelle fuer
Experimentelle Ophthalmologie. Roentgenweg 11,
Tuebingen, D-72076. Germany <http://orlab.optom.
unsw.edu.au/ICVS>.
National Society to Prevent Blindness. 500 East Remington
Rd., Schaumburg, IL 60173. (708) 843-2020 or (800)
331-2020. <http://www.preventblindness.org>.
OTHER

‘‘Breaking the Code of Color.’’ Seeing, Hearing and Smelling
the World. <http://www.hhmi.org/senses/b/
b130.htm>.
‘‘Color Blindness.’’ Geocities. <http://www.geocities.com/
Heartland/8833/coloreye.html>.
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Ostomy is a surgical procedure used to create an
opening for urine and feces to be released from the
body. Colostomy refers to a surgical procedure where
a portion of the large intestine is brought through the
abdominal wall to carry stool out of the body.

Purpose
A colostomy is created as a means to treat various
disorders of the large intestine, including cancer,
obstruction, inflammatory bowel disease, ruptured
diverticulum, ischemia (compromised blood supply),
or traumatic injury. Temporary colostomies are created to divert stool from injured or diseased portions
of the large intestine, allowing rest and healing.
Permanent colostomies are performed when the distal
bowel (bowel at the farthest distance) must be
removed or is blocked and inoperable. Although colorectal cancer is the most common indication for a
permanent colostomy, only about 10–15% of patients
with this diagnosis require a colostomy.

Description
Surgery will result in one of three types of
colostomies:


End colostomy. The functioning end of the intestine
(the section of bowel that remains connected to the
upper gastrointestinal tract) is brought out onto the
surface of the abdomen, forming the stoma by cuffing
the intestine back on itself and suturing the end to the
skin. A stoma is an artificial opening created to the
surface of the body. The surface of the stoma is actually the lining of the intestine, usually appearing moist
and pink. The distal portion of bowel (now connected
947

Colostomy

KEY TERMS

Colostomy

only to the rectum) may be removed, or sutured closed
and left in the abdomen. An end colostomy is usually
a permanent ostomy, resulting from trauma, cancer or
another pathological condition.


Double–barrel colostomy. This colostomy involves
the creation of two separate stomas on the abdominal
wall. The proximal (nearest) stoma is the functional
end that is connected to the upper gastrointestinal
tract and will drain stool. The distal stoma, connected
to the rectum and also called a mucous fistula, drains
small amounts of mucus material. This is most often a
temporary colostomy performed to rest an area of
bowel, and to be later closed.



Loop colostomy. This colostomy is created by bringing a loop of bowel through an incision in the
abdominal wall. The loop is held in place outside
the abdomen by a plastic rod slipped beneath it. An
incision is made in the bowel to allow the passage of
stool through the loop colostomy. The supporting
rod is removed approximately 7–10 days after surgery, when healing has occurred that will prevent the
loop of bowel from retracting into the abdomen. A
loop colostomy is most often performed for creation
of a temporary stoma to divert stool away from an
area of intestine that has been blocked or ruptured.

Preparation
As with any surgical procedure, the patient will be
required to sign a consent form after the procedure is
explained thoroughly. Blood and urine studies, along
with various x rays and an electrocardiograph (EKG),
may be ordered as the doctor deems necessary. If
possible, the patient should visit an enterostomal
therapist, who will mark an appropriate place on the
abdomen for the stoma, and offer pre-operative education on ostomy management.
In order to empty and cleanse the bowel, the
patient may be placed on a low residue diet for several
days prior to surgery. A liquid diet may be ordered for
at least the day before surgery, with nothing by mouth
after midnight. A series of enemas and/or oral preparations (GoLytely or Colyte) may be ordered to empty the
bowel of stool. Oral anti-infectives (neomycin, erythromycin, or kanamycin sulfate) may be ordered to
decrease bacteria in the intestine and help prevent
post-operative infection. A nasogastric tube is inserted
from the nose to the stomach on the day of surgery or
during surgery to remove gastric secretions and prevent
nausea and vomiting. A urinary catheter (a thin plastic
tube) may also be inserted to keep the bladder empty
during surgery, giving more space in the surgical field
and decreasing chances of accidental injury.
948

Aftercare
Post-operative care for the patient with a new
colostomy, as with those who have had any major
surgery, involves monitoring of blood pressure,
pulse, respirations, and temperature. Breathing tends
to be shallow because of the effect of anesthesia and
the patient’s reluctance to breathe deeply and experience pain that is caused by the abdominal incision. The
patient is instructed how to support the operative site
during deep breathing and coughing, and given pain
medication as necessary. Fluid intake and output is
measured, and the operative site is observed for color
and amount of wound drainage. The nasogastric tube
will remain in place, attached to low intermittent suction until bowel activity resumes. For the first 24–48
hours after surgery, the colostomy will drain bloody
mucus. Fluids and electrolytes are infused intravenously until the patient’s diet is can gradually be
resumed, beginning with liquids. Usually within
72 hours, passage of gas and stool through the stoma
begins. Initially the stool is liquid, gradually thickening as the patient begins to take solid foods. The
patient is usually out of bed in 8–24 hours after surgery
and discharged in 2–4 days.
A colostomy pouch will generally have been
placed on the patient’s abdomen, around the stoma
during surgery. During the hospital stay, the patient
and his or her caregivers will be educated on how to
care for the colostomy. Determination of appropriate
pouching supplies and a schedule of how often to
change the pouch should be established. Regular
assessment and meticulous care of the skin surrounding the stoma is important to maintain an adequate
surface on which to apply the pouch. Some patients
with colostomies are able to routinely irrigate the
stoma, resulting in regulation of bowel function;
rather than needing to wear a pouch, these patients
may need only a dressing or cap over their stoma.
Often, an enterostomal therapist will visit the patient
at home after discharge to help with the patient’s
resumption of normal daily activities.

Risks
Potential complications of colostomy surgery
include:


excessive bleeding



surgical wound infection



thrombophlebitis (inflammation and blood clot to
veins in the legs)



pneumonia
GALE ENCYCLOPEDIA OF MEDICINE

Colostomy

Colon
Closed incision

Catheter

Glass rod
Colostomy bag

A colostomy is a surgical procedure in which a portion of the large intestine, or colon, is brought through the abdominal wall to
carry feces out of the body. There are three types of colostomies: end colostomy, double-barrel colostomy, and loop colostomy.
The loop colostomy is featured in the illustration above. (Illustration by Electronic Illustrators Group.)



pulmonary embolism (blood clot or air bubble in the
lungs’ blood supply)

Normal results
Complete healing is expected without complications. The period of time required for recovery from
the surgery may vary depending of the patient’s overall health prior to surgery. The colostomy patient
without other medical complications should be able
to resume all daily activities once recovered from the
surgery.

Abnormal results
The doctor should be made aware of any of the
following problems after surgery:
GALE ENCYCLOPEDIA OF MEDICINE



increased pain, swelling, redness, drainage, or bleeding in the surgical area.



headache, muscle aches, dizziness, or fever.



increased abdominal pain or swelling, constipation,
nausea or vomiting or black, tarry stools
Stomal complications to be monitored include:



Death (necrosis) of stomal tissue. Caused by inadequate blood supply, this complication is usually visible 12–24 hours after the operation and may require
additional surgery.



Retraction (stoma is flush with the abdomen surface
or has moved below it). Caused by insufficient stomal length, this complication may be managed by use
of special pouching supplies. Elective revision of the
stoma is also an option.
949

Colposcopy

KEY TERMS
Diverticulum—Pouches that project off the wall of
the intestine, visible as opaque on an x ray after the
patient has swallowed a contrast (dye) substance.
Embolism—Blockage of a blood vessel by any small
piece of material traveling in the blood. The emboli
may be caused by germs, air, blood clots, or fat.
Enema—Insertion of a tube into the rectum to
infuse fluid into the bowel and encourage a bowel
movement. Ordinary enemas contain tap water,
mixtures of soap and water, glycerine and water,
or other materials.
Intestine—Commonly called the bowels, divided
into the small and large intestine. They extend from
the stomach to the anus. The small intestine is
about 20 ft (6 m) long. The large intestine is about
5 ft (1.5 m) long.
Ischemia—A compromise in blood supply delivered
to body tissues that causes tissue damage or death.
Ostomy—A surgically created opening in the abdomen for elimination of waste products (urine or stool).



Prolapse (stoma increases length above the surface of
the abdomen). Most often results from an overly large
opening in the abdominal wall or inadequate fixation
of the bowel to the abdominal wall. Surgical correction is required when blood supply is compromised.



Stenosis (narrowing at the opening of the stoma).
Often associated with infection around the stoma
or scarring. Mild stenosis can be removed under
local anesthesia. Severe stenosis may require surgery
for reshaping the stoma.



Parastomal hernia (bowel causing bulge in the
abdominal wall next to the stoma). This is due to
placement of the stoma where the abdominal wall is
weak or creation of an overly large opening in the
abdominal wall. The use of an ostomy support belt
and special pouching supplies may be adequate. If
severe, the defect in the abdominal wall should be
repaired and the stoma moved to another location.

Resources
ORGANIZATIONS

United Ostomy Association, Inc. (UOA). 19772
MacArthur Blvd., Suite 200, Irvine, CA 92612-2405.
(800) 826-0826. <http://www.uoa.org>.

Kathleen D. Wright, RN
950

I Colposcopy
Definition
Colposcopy is a procedure that allows a physician
to take a closer look at a woman’s cervix and vagina
using a special instrument called a colposcope. It is
used to check for precancerous or abnormal areas.
The colposcope can magnify the area between 10 and
40 times; some devices also can take photographs.

Purpose
The colposcope helps to identify abnormal areas
of the cervix or vagina so that small pieces of tissue
(biopsies) can be taken for further analysis.
Colposcopy is used to identify or rule out the existence of any precancerous conditions in the cervical
tissue. If a Pap test shows abnormal cell growth, further
testing, such as colposcopy, often is required. A Pap test
is a screening test that involves scraping cells from the
outside of the cervix. If abnormal cells are found, the
physician will attempt to find the area that produced
the abnormal cells and remove it for further study
(biopsy). Only then can a diagnosis be made.
Colposcopy may also be performed if the cervix
looks abnormal during a routine examination. It may
also be suggested for women with genital warts and for
diethylstilbestrol (DES) daughters (women whose
mothers took DES when pregnant with them).

Precautions
Women who are pregnant, or who suspect that
they are pregnant, must tell their doctor before the
procedure begins. Pregnant women can, and should,
have a colposcopy if they have an abnormal Pap test.
However, special precautions must be taken during
biopsy of the cervix.

Description
A colposcopy is performed in a physician’s office
and is similar to a regular gynecologic exam. An
instrument called a speculum is used to hold the
vagina open, and the gynecologist looks at the cervix
and vagina through the colposcope instead simply by
eye, as in a routine examination.
The colposcope is placed outside the patient’s body
and never touches the skin. The cervix and vagina are
swabbed with dilute acetic acid (vinegar). The solution
highlights abnormal areas by turning them white
(instead of a normal pink color). Abnormal areas can
GALE ENCYCLOPEDIA OF MEDICINE

If any abnormal areas are seen, the doctor will
take a biopsy of the tissue, a common procedure that
takes about 15 minutes. Several samples might be
taken, depending on the size of the abnormal area.
A biopsy may cause temporary discomfort and cramping, which usually go away within a few minutes. If the
abnormal area appears to extend inside the cervical
canal, a scraping of the canal may be done. The biopsy
results are usually available within a week.
If the tissue sample indicates abnormal growth
(dysplasia) or precancer, and if the entire abnormal
area can be seen, the doctor can destroy the tissue
using one of several procedures, including ones that
use high heat (diathermy), extreme cold (cryotherapy),
or lasers. Another procedure, called a loop electrosurgical excision (LEEP), uses low-voltage high-frequency
radio waves to excise tissue. If any of the abnormal
tissue is within the cervical canal, a cone biopsy
(removal of a conical section of the cervix for inspection) will be needed.

Colposcopy

also be identified by looking for a characteristic pattern
made by abnormal blood vessels. In 2004, a study
showed that a new optical detection system used with
colposcopy greatly improved visual detection of precancerous changes in the cervix during the procedure.

A colposcopy makes it possible for a physician to view this
healthy cervix without surgery. (Photograph by Dr. P. Marazzi,
Custom Medical Stock Photo. Reproduced by permission.)

Preparation
Colposcopy is a painless procedure that does not
require any anesthetic medication. If a biopsy is done,
there may be mild cramps or a sharp pinching when the
tissue is removed. To lessen this pain, your doctor may
recommend 800 mg of ibuprofen (Motrin) taken the
night before and the morning of the procedure (no later
than 30 minutes before the appointment). Patients who
are pregnant or allergic to aspirin or ibuprofen can take
two tablets of acetaminophen (Tylenol) instead.

Aftercare
If a biopsy was done, there may be a dark vaginal
discharge afterwards. After the sample is removed, the
doctor applies Monsel’s solution to the area to stop
the bleeding. When this mixes with blood it creates a
black fluid that looks like coffee grounds for a couple
of days after the procedure. It is also normal to have
some spotting after a colposcopy.
Patients should not use tampons or put anything
else in the vagina for at least a week after the procedure, or until the doctor says it is safe. In addition,
women should not have sex or douche for at least a
week after the procedure because of the risk of
infection.
GALE ENCYCLOPEDIA OF MEDICINE

This colposcopic view of the cervix reveals CIN 2 dysplasia,
or abnormal growth of cells. This is the second stage in the
development of cervical cancer. (Custom Medical Stock Photo.
Reproduced by permission.)

Risks
Occasionally, patients may have bleeding or infection after biopsy. Bleeding is usually controlled with a
topical medication.
A patient should call her doctor right away if she
notices any of the following symptoms:


heavy vaginal bleeding (more than one sanitary pad
an hour)



fever, chills, or an unpleasant vaginal odor



lower abdominal pain

Normal results
If visual inspection shows that the surface of the
cervix is smooth and pink, this is considered normal. If
951

Coma

Resources

KEY TERMS
Biopsy—Removal of sample of abnormal tissue for
more extensive examination under a microscope.
Cervix—The neck of the uterus.
Cryotherapy—Freezing and destroying abnormal
cells.
DES—The abbreviation for diethylstilbestrol, a synthetic form of estrogen that was widely prescribed to
women from 1940 to 1970 to prevent complications.
It was linked to several serious birth defects and
disorders of the reproductive system in daughters of
women who took DES. In 1971, the FDA suggested it
not be used during pregnancy and banned its use in
1979 as a growth promoter in livestock.
Diathermy—Also called electrocautery, this is a
procedure that heats and destroys abnormal cells.
It is gradually being replaced by cryosurgery,
lasers, or LEEP.
Human papilloma virus—A virus that causes common warts of the hands and feet, as well as lesions
in the genital and vaginal area. More than 50 types
of HPV have been identified, some of which are
linked to cancerous and precancerous conditions,
including cancer of the cervix.
Loop electrosurgical excision (LEEP)—A procedure that can help diagnose and treat cervical
abnormalities, using a thin wire loop that emits a
low-voltage high-frequency radio wave that can
excise tissue. It is considered better than either
lasers or electrocautery because it can both diagnose and treat precancerous cells or early stage
cancer at the same time.
Pap test—The common term for the Papanicolaou
test, a simple smear method of examining stained
cells to detect cancer of the cervix.
Speculum—A retractor used to separate the walls
of the vagina to make visual examination easier.

abnormal areas are found and biopsied and the results
show no indication of cancer, a precancerous condition, or other disease, this also is considered normal.

Abnormal results
Abnormal conditions that can be detected using
colposcopy and biopsy include precancerous tissue
changes (cervical dysplasia), cancer, and cervical
warts (human papilloma virus).
952

PERIODICALS

‘‘Optical Detection System With Colposcopy Improves
Cervical Cancer Detection.’’ Cancer Weekly March 9,
2004: 51.
ORGANIZATIONS

American Society for Colposcopy and Cervical Pathology.
20 W. Washington St., Ste. #1, Hagerstown, MD
21740. (800) 787-7227. <http://www.asccp.org>.

Carol A. Turkington
Teresa G. Odle

I Coma
Definition
Coma, from the Greek word ‘‘koma,’’ meaning
deep sleep, is a state of extreme unresponsiveness, in
which an individual exhibits no voluntary movement
or behavior. Furthermore, in a deep coma, even painful stimuli (actions which, when performed on a
healthy individual, result in reactions) are unable to
affect any response, and normal reflexes may be lost.

Description
Coma lies on a spectrum with other alterations in
consciousness. The level of consciousness required by,
for example, someone reading this passage lies at one
extreme end of the spectrum, while complete brain
death lies at the other end of the spectrum. In between
are such states as obtundation, drowsiness, and stupor. All of these are conditions which, unlike coma,
still allow the individual to respond to stimuli,
although such a response may be brief and require
stimulus of greater than normal intensity.
In order to understand the loss of function suffered by a comatose individual, it is necessary to first
understand the important characteristics of the conscious state. Consciousness is defined by two fundamental elements: awareness and arousal.
Awareness allows one to receive and process all
the information communicated by the five senses, and
thus relate to oneself and to the outside world.
Awareness has both psychological and physiological
components. The psychological component is governed by an individual’s mind and mental processes.
The physiological component refers to the functioning
of an individual’s brain, and therefore that brain’s
GALE ENCYCLOPEDIA OF MEDICINE

Arousal is regulated solely by physiological functioning and consists of more primitive responsiveness to
the world, as demonstrated by predictable reflex (involuntary) responses to stimuli. Arousal is maintained by
the reticular activating system (RAS). This is not an
anatomical area of the brain, but rather a network of
structures (including the brainstem, the medulla, and
the thalamus) and nerve pathways, which function
together to produce and maintain arousal.

Causes and symptoms
Coma, then, is the result of something that interferes
with the functioning of the cerebral cortex and/or the
functioning of the structures which make up the RAS. In
fact, a huge and varied number of conditions can result
in coma. A good way of categorizing these conditions is
to consider the anatomic and the metabolic causes of
coma. Anatomic causes of coma are those conditions
that disrupt the normal physical architecture of the brain
structures responsible for consciousness, either at the
level of the cerebal cortex or the brainstem, while metabolic causes of coma consist of those conditions that
change the chemical environment of the brain, thereby
adversely affecting function.
There are many metabolic causes of coma,
including:


A decrease in the delivery to the brain of substances
necessary for appropriate brain functioning, such as
oxygen, glucose (sugar), and sodium.



The presence of certain substances that disrupt the
functioning of neurons. Drugs or alcohol in toxic
quantities can result in neuronal dysfunction, as can
substances normally found in the body, but that, due
to some diseased state, accumulate at toxic levels.
Accumulated substances that might cause coma
include ammonia due to liver disease, ketones due
to uncontrolled diabetes, or carbon dioxide due to a
severe asthma attack.



The changes in chemical levels in the brain due to the
electrical derangements caused by seizures.

Diagnosis
As in any neurologic condition, history and examination form the cornerstone of diagnosis when the
patient is in a coma; however, history must be
GALE ENCYCLOPEDIA OF MEDICINE

obtained from family, friends, or EMS. The Glasgow
Coma Scale is a system of examining a comatose
patient. It is helpful for evaluating the depth of the
coma, tracking the patient’s progress, and predicting
(somewhat) the ultimate outcome of the coma. The
Glasgow Coma Scale assigns a different number of
points for exam results in three different categories:
opening the eyes, verbal response (using words or
voice to respond), and motor response (moving a
part of the body). Fifteen is the largest possible number of total points, indicating the highest level of functioning. The highest level of functioning would be
demonstrated by an individual who spontaneously
opens his/her eyes, gives appropriate answers to questions about his/her situation, and can carry out a
command (such as ‘‘move your leg’’ or ‘‘nod your
head’’). Three is the least possible number of total
points and would be given to a patient for whom not
even a painful stimulus is sufficient to provoke a
response. In the middle are those patients who may
be able to respond, but who require an intense or
painful stimulus, and whose response may demonstrate some degree of brain malfunctioning (such as a
person whose only response to pain in a limb is to bend
that limb in toward the body). When performed as
part of the admission examination, a Glasgow score
of three to five points often suggests that the patient
has likely suffered fatal brain damage, while eight or
more points indicates that the patient’s chances for
recovery are good. Expansion of the pupils and
respiratory pattern are also important. Metabolic
causes of coma are diagnosed from blood work and
urinalysis to evaluate blood chemistry, drug screen,
and blood cell abnormalities that may indicate infection. Anatomic causes of coma are diagnosed from
CT (computed tomography) or MRI (magnetic resonance imaging) scans.

Treatment
Coma is a medical emergency, and attention must
first be directed to maintaining the patient’s respiration and circulation, using intubation aand ventilation, administration of intravenous fluids or blood as
needed, and other supportive care. If head trama has
not been excluded, the neck should be stablized in the
event of fracture. It is obviously extremely important
for a physician to determine quickly the cause of a
coma, so that potentially reversible conditions are
treated immediately. For example, an infection may
be treated with antibiotics; a brain tumor may be
removed; and brain swelling from an injury can be
reduced with certain medications. Various metabolic
disorders can be addressed by supplying the individual
953

Coma

physical and chemical condition. Awareness is regulated by cortical areas within the cerebral hemispheres,
the outermost layer of the brain that separates humans
from other animals by allowing for greater intellectual
functioning.

Coma

Cortex

Thalamus

Mid-brain reticular
formation

A side-view of the brain, showing movement
of the reticular activating substance (RAS)
essential to consciousness
Diffuse and bilateral damage to the cerebral cortex
(relative preservation of brain-stem reflexes)

Mass lesions in this region resulting in
compression of the brain-stem and damage
to the reticular activating substance (RAS)

Brain-stem
compression

Possible causes
• Damage due to lack of oxygen or restricted blood flow, perhaps
resulting from cardiac arrest, an anaesthetic accident, or shock
• Damage incurred from metabolic processes associated with
kidney or liver failure, or with hypoglycemia
• Trauma damage
• Damage due to a bout with meningitis, encephalomyelitis, or a
severe systemic infection

Structural lesions within this region also resulting
in compression of the brain-stem and damage to
the reticular activating substance (RAS)

Lesions within the brain-stem directly suppressing
the reticular activating substance (RAS)

Local brain-stem
pressure
Symmetrical
depression of
brain-stem reflexes

Asymmetrical brainstem signs
Possible causes • Cerebellar tumors, abscesses, or hemorrhages

Possible causes • Drug overdosage

The four brain conditions that result in coma. (Illustration by Hans & Cassady.)

954

GALE ENCYCLOPEDIA OF MEDICINE

Anatomic—Related to the physical structure of an
organ or organism.
Metabolic—Refers to the chemical processes of an
organ or organism.
Neuron—The cells within the body which make up
the nervous system, specifically those along which
information travels.
Physiological—Pertaining to the functioning of an
organ, as governed by the interactions between its
physical and chemical conditions.
Psychological—Pertaining to the mind, its mental
processes, and its emotional makeup.
Stimulus/stimuli—Action or actions performed on
an individual which predictably provoke(s) a
reaction.

states in which the individual loses all ability to function and remains deeply unresponsive. An individual
who has suffered such a severe brain injury may
remain in a coma indefinitely. This condition is termed
persistent vegetative state.
Outcome from a coma is therefore quite variable
and depends a great deal on the cause and duration of
the coma. In the case of drug poisonings, extremely
high rates of recovery can be expected following
prompt medical attention. Patients who have suffered
head injuries tend to do better than do patients whose
coma was caused by other types of medical illnesses.
Leaving out those people whose coma followed drug
poisoning, only about 15% of patients who remain in a
coma for more than just a few hours make a good
recovery. Those adult patients who remain in a coma
for greater than four weeks have almost no chance of
eventually regaining their previous level of functioning.
On the other hand, children and young adults have
regained functioning even after two months in a coma.
Resources

with the correct amount of oxygen, glucose, or
sodium; by treating the underlying disease in liver
disease, asthma, or diabetes; and by halting seizures
with medication. Because of their low incidence of side
effects and potential for prompt reversal of coma in
certain conditions, glucose, the B-vitamin thiamine,
and Narcan (to counteract any narcotic-type drugs)
are routinely given.

Prognosis
Some conditions that cause coma can be completely reversed, restoring the individual to his or her
original level of functioning. However, if areas of the
brain have been sufficiently damaged due to the severity or duration of the condition which led to the coma,
the individual may recover from the coma with permanent disabilities, or may even never regain consciousness. Take, for example, the situation of
someone whose coma was caused by brain injury in a
car accident. Such an injury can result in one of three
outcomes. In the event of a less severe brain injury,
with minimal swelling, an individual may indeed
recover consciousness and regain all of his or her
original abilities. In the event of a more severe brain
injury, with swelling that resulted in further pressure
on areas of the brain, an individual may regain consciousness, but may have some degree of impairment.
The impairment may be physical (such as paralysis of a
leg) or may even result in a change in the individual’s
intellectual functioning and/or personality. The most
severe types of brain injury, short of death, result in
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave.,
St. Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.
Coma Recovery Association, Inc. 570 Elmont Rd., Suite
104, Elmont, NY 11003. (516) 355-0951.

Rosalyn Carson-DeWitt, MD

Combat neurosis see Post-traumatic stress
disorder

I Common cold
Definition
The common cold is a viral infection of the upper
respiratory system, including the nose, throat, sinuses,
eustachian tubes, trachea, larynx, and bronchial tubes.
Although more than 200 different viruses can cause a
cold, 30–50% are caused by a group known as rhinoviruses. Almost all colds clear up in less than two
weeks without complications.

Description
Colds, sometimes called rhinovirus or coronavirus infections, are the most common illness to strike
any part of the body. It is estimated that the average
955

Common cold

KEY TERMS

Common cold

person has more than 50 colds during a lifetime.
Anyone can get a cold, although pre-school and
grade school children catch them more frequently
than adolescents and adults. Repeated exposure to
viruses causing colds creates partial immunity.
Although most colds resolve on their own without
complications, they are a leading cause of visits to the
doctor and of time lost from work and school.
Treating symptoms of the common cold has given
rise to a multi-million dollar industry in overthe-counter medications.
Cold season in the United States begins in early
autumn and extends through early spring. Although it
is not true that getting wet or being in a draft causes a
cold (a person has to come in contact with the virus to
catch a cold), certain conditions may lead to increased
susceptibility. These include:


fatigue and overwork



emotional stress



poor nutrition



smoking



living or working in crowded conditions

Colds make the upper respiratory system less
resistant to bacterial infection. Secondary bacterial
infection may lead to middle ear infection, bronchitis,
pneumonia, sinus infection, or strep throat. People with
chronic lung disease, asthma, diabetes, or a weakened
immune system are more likely to develop these
complications.

Causes and symptoms

Cold Remedies

Antihistamines

Decongestants

Symptoms

Side-effects

Congestion
Itchy eyes
Runny nose
Sneezing
Stuffy nose
Congestion
Stuffy nose

Drowsiness
Dry mouth and eyes

Insomnia
Rapid heart beat
Stimulation

eyes, the virus is transferred to an environment where
it can reproduce and cause a cold.
Finally, cold viruses can be spread through inanimate objects (door knobs, telephones, toys) that
become contaminated with the virus. This is a common method of transmission in child care centers. If a
child with a cold touches her runny nose, then plays
with a toy, some of the virus may be transferred to the
toy. When another child plays with the toy a short time
later, he may pick up some of the virus on his hands.
The second child then touches his contaminated hands
to his eyes, nose, or mouth and transfers some of the
cold virus to himself.
Once acquired, the cold virus attaches itself to the
lining of the nasal passages and sinuses. This causes
the infected cells to release a chemical called histamine.
Histamine increases the blood flow to the infected
cells, causing swelling, congestion, and increased
mucus production. Within one to three days the
infected person begins to show cold symptoms.

Colds are caused by more than 200 different
viruses. The most common groups are rhinoviruses
and coronaviruses. Different groups of viruses are
more infectious at different seasons of the year, but
knowing the exact virus causing the cold is not important in treatment.

The first cold symptoms are a tickle in the throat,
runny nose, and sneezing. The initial discharge from
the nose is clear and thin. Later it changes to a thick
yellow or greenish discharge. Most adults do not
develop a fever when they catch a cold. Young children may develop a low fever of up to 102  F (38.9  C).

People with colds are contagious during the first
two to four days of the infection. Colds pass from
person to person in several ways. When an infected
person coughs, sneezes, or speaks, tiny fluid droplets
containing the virus are expelled. If these are breathed
in by other people, the virus may establish itself in
their noses and airways.

In addition to a runny nose and fever, signs of
a cold include coughing, sneezing, nasal congestion,
headache, muscle ache, chills, sore throat, hoarseness,
watery eyes, tiredness, and lack of appetite. The cough
that accompanies a cold is usually intermittent and dry.

Colds may also be passed through direct contact.
If a person with a cold touches his runny nose or
watery eyes, then shakes hands with another person
some of the virus is transferred to the uninfected person. If that person then touches his mouth, nose, or
956

Most people begin to feel better four to five days
after their cold symptoms become noticeable. All
symptoms are generally gone within ten days, except
for a dry cough that may linger for up to three weeks.
Colds make people more susceptible to bacterial
infections such as strep throat, middle ear infections,
and sinus infections. A person whose cold does not
GALE ENCYCLOPEDIA OF MEDICINE

People who have emphysema, chronic lung disease, diabetes, or a weakened immune system — either
from diseases such as AIDS or leukemia, or as the
result of medications, (corticosteroids, chemotherapy
drugs)—should consult their doctor if they get a
cold. People with these health problems are more
likely to get a secondary infection.

Diagnosis
Colds are diagnosed by observing a person’s
symptoms. There are no laboratory tests readily available to detect the cold virus. However, a doctor may
do a throat culture or blood test to rule out a secondary
infection.
Influenza is sometimes confused with a cold, but
flu causes much more severe symptoms and generally a
fever. Allergies to molds or pollens also can make the
nose run. Allergies are usually more persistent than the
common cold. An allergist can do tests to determine if
the cold-like symptoms are being caused by an allergic
reaction. Also, some people get a runny nose when
they go outside in winter and breathe cold air. This
type of runny nose is not a symptom of a cold.

Treatment
There are no medicines that will cure the common
cold. Given time, the body’s immune system will make
antibodies to fight the infection, and the cold will be
resolved without any intervention. Antibiotics are useless against a cold. However, a great deal of money is
spent by pharmaceutical companies in the United
States promoting products designed to relieve cold
symptoms. These products usually contain antihistamines, decongestants, and/or pain relievers.
Antihistamines block the action of the chemical
histamine that is produced when the cold virus
invades the cells lining the nasal passages.
Histamine increases blood flow and causes the cells
to swell. Antihistamines are taken to relieve the
symptoms of sneezing, runny nose, itchy eyes, and
congestion. Side effects are dry mouth and drowsiness, especially with the first few doses.
Antihistamines should not be taken by people who
GALE ENCYCLOPEDIA OF MEDICINE

are driving or operating dangerous equipment. Some
people have allergic reactions to antihistamines.
Common over-the-counter antihistamines include
Chlor-Trimeton, Dimetapp, Tavist, and Actifed.
The generic name for two common antihistamines
are chlorpheniramine and diphenhydramine.
Decongestants work to constrict the blood flow to
the vessels in the nose. This can shrink the tissue,
reduce congestion, and open inflamed nasal passages,
making breathing easier. Decongestants can make
people feel jittery or keep them from sleeping. They
should not be used by people with heart disease, high
blood pressure, or glaucoma. Some common decongestants are Neo-Synepherine, Novafed, and Sudafed.
The generic names of common decongestants include
phenylephrine, phenylpropanolamine, pseudoephedrine, and in nasal sprays naphazoline, oxymetazoline
and xylometazoline.
Many over-the-counter medications are combinations of both antihistamines and decongestants; an
ache and pain reliever, such as acetaminophen
(Datril, Tylenol, Panadol) or ibuprofen (Advil,
Nuprin, Motrin, Medipren); and a cough suppressant
(dextromethorphan). Common combination medications include Tylenol Cold and Flu, Triaminic,
Sudafed Plus, and Tavist D. Aspirin should not be
given to children with a cold because of its association
with a risk of Reye’s syndrome, a serious disease.
Nasal sprays and nose drops are other products
promoted for reducing nasal congestion. These
usually contain a decongestant, but the decongestant
can act more quickly and strongly than ones found in
pills or liquids because it is applied directly in the nose.
Congestion returns after a few hours.
People can become dependent on nasal sprays and
nose drops. If used for a long time, users may suffer
withdrawal symptoms when these products are discontinued. Nasal sprays and nose drops should not
be used for more than a few days. The label lists
recommendations on length and frequency of use.
Scientists reported in 2004 the possibility of a new
oral drug for use in relieving common cold symptoms.
Called pleconaril, it inhibited viral replication in at
least 90% of rhinoviruses if taken within 24 hours of
onset.
People react differently to different cold medications and may find some more helpful than others. A
medication may be effective initially, then lose some of
its effectiveness. Children sometimes react differently
than adults. Over-the-counter cold remedies should
not be given to infants without consulting a doctor
first.
957

Common cold

begin to improve within a week; or who experiences
chest pain, fever for more than a few days, difficulty
breathing, bluish lips or fingernails, a cough that
brings up greenish-yellow or grayish sputum, skin
rash, swollen glands, or whitish spots on the tonsils
or throat should consult a doctor to see if he or she has
acquired a secondary bacterial infection that needs to
be treated with an antibiotic.

Common cold

Care should be taken not to exceed the recommended dosages, especially when combination medications or nasal sprays are taken. Individuals should
determine whether they wish to use any of these drugs.
None of them shorten or cure a cold. At best they help
a person feel more comfortable. People who are confused about the drugs in any over-the-counter
cold remedies should ask their pharmacist for an
explanation.



Taking coneflower or goldenseal (Hydrastis canadensis). Other useful herbs to reduce symptoms include
yarrow (Achillea millefolium), eyebright (Euphrasia
officinalis), garlic (Allium sativum), and onions
(Allium cepa). (Herbal)



Microdoses of Viscue album, Natrum muriaticum,
Allium cepa, or Nux vomica. (Homeopathy)



Taking yin chiao (sometimes transliterated as yinquiao) tablets that contain honeysuckle and forsythia when symptoms appear. Natural herb loquat
syrup for cough and sinus congestion and Chinese
ephedra (ma-huang) for runny nose. (Chinese traditional medicine)



The use of zinc lozenges every two hours along with
high doses of vitamin C is suggested. Some practitioners also suggest eliminating dairy products for
the duration of the cold. (Nutritional therapy).

In addition to the optional use of over the counter
cold remedies, there are some self-care steps that people can take to ease their discomfort. These include:


drinking plenty of fluids, but avoiding acidic juices,
which may irritate the throat



gargling with warm salt water — made by adding one
teaspoon of salt to 8 oz of water — for a sore throat



not smoking



getting plenty of rest



using a cool-mist room humidifier to ease congestion
and sore throat



rubbing Vaseline or other lubricant under the nose to
prevent irritation from frequent nose blowing



for babies too young to blow their noses, the mucus
should be suctioned gently with an infant nasal
aspirator. It may be necessary to soften the mucus
first with a few drops of salt water.

The use of zinc lozenges may be moving toward
acceptance by practitioners of traditional medicine. In
1996 the Cleveland Clinic tested zinc gluconate
lozenges and found using zinc in the first 24 hours
after cold symptoms occurred shortened the duration
of symptoms. The mechanism by which zinc worked
was not clear, but additional studies are underway.
At one time, the herb (Echinacea spp.) was touted
as a remedy to relieve cold symptoms. However, a
study published in 2004 reported that the herb failed
to relieve cold symptoms in 400 children taking it and
caused skin rashes in some children.

Alternative treatment
Alternative practitioners emphasize that people
get colds because their immune systems are weak.
They point out that everyone is exposed to cold
viruses, but not everyone gets every cold. The difference seems to be in the ability of the immune system to
fight infection. Prevention focuses on strengthening
the immune system by eating a healthy diet low in
sugars and high in fresh fruits and vegetables, practicing meditation to reduce stress, and getting regular
moderate exercise.
Once cold symptoms appear, some naturopathic
practitioners believe the symptoms should be allowed
to run their course without interference. Others suggest the following:




Inhaling a steaming mixture of lemon oil, thyme
oil, eucalyptus, and tea tree oil (Melaleuca spp.).
(Aromatherapy)
Gargling with a mixture of water, salt, and turmeric
powder or astringents such as alum, sumac, sage, and
bayberry to ease a sore throat. (Ayurvedic medicine)

958

Prognosis
Given time, the body will make antibodies to cure
itself of a cold. Most colds last a week to 10 days. Most
people start feeling better within four or five days.
Occasionally a cold will lead to a secondary bacterial
infection that causes strep throat, bronchitis, pneumonia, sinus infection, or a middle ear infection. These
conditions usually clear up rapidly when treated with
an antibiotic.

Prevention
It is not possible to prevent colds because the
viruses that cause colds are common and highly infectious. However, there are some steps individuals can
take to reduce their spread. These include:


washing hands well and frequently, especially after
touching the nose or before handling food



covering the mouth and nose when sneezing



disposing of used tissues properly
GALE ENCYCLOPEDIA OF MEDICINE

Bronchial tubes—The major airways to the lungs
and their main branches.
Coronavirus—a genus of viruses that cause respiratory disease and gastroenteritis.
Corticosteroids—A group of hormones produced
naturally by the adrenal gland or manufactured
synthetically. They are often used to treat inflammation. Examples include cortisone and
prednisone.
Eustachian tube—A thin tube between the middle
ear and the pharynx. Its purpose is to equalize
pressure on either side of the ear drum.
Rhinovirus—A virus that infects the upper respiratory system and causes the common cold.



avoiding close contact with someone who has a
cold during the first two to four days of their
infection



not sharing food, eating utensils, or cups with
anyone



avoiding crowded places where cold germs can
spread



eating a healthy diet and getting adequate sleep

Resources
PERIODICALS

‘‘Study: Echinacea Is Ineffective.’’ Chain Drug Review
February 16, 2004: 25.
Zepf, Bill. ‘‘Pleconaril for Treatment of the Common Cold?’’
American Family Physician February 1, 2004: 703.

Tish Davidson, A.M.
Teresa G. Odle

Immunodeficiency means that the immune system
is deficient in one or more of its components and is
unable to respond effectively. Common variable
immunodeficiency is the most common of the immunodeficiency disorders. Patients with this disease have
frequent infections, especially those caused by the
same microorganism. Recurring infections are an indication that the immune system is not responding
normally and developing immunity to reinfection.
Patients with common variable immunodeficiency
have a normal number of B cells, the lymphocytes
that make antibodies. In approximately one-third of
these patients, the number of B cells in the blood that
have IgG antibodies on their surface is lower than
normal, but there are normal numbers of B cells in
their bone marrow. B cells with IgG antibodies on
their surface are capable of responding to microorganisms. The lack of IgG on the surface of the B cells
means that they are not prepared to fight infection.
The T-cell lymphocytes, those cells responsible for
cellular immunity, are usually normal, although
some cell signal components may be lacking.

Causes and symptoms
The cause of common variable immunodeficiency
is not known, although some forms seem to be hereditary. The main symptom is recurring infections that
tend to be chronic rather than acute. Patients may also
develop diarrhea and, as a consequence of the diarrhea, do not absorb food efficiently. This can lead to
malnourishment that can aggravate the disorder.
Common variable immunodeficiency normally
appears in children after the age of 10. Autoimmune
disorders such as rheumatoid arthritis, thyroiditis, and
systemic lupus erythematosus and certain cancers such
as lymphomas and leukemias may be associated with
common variable immunodeficiency.

Diagnosis

variable
I Common
immunodeficiency
Definition
Common variable immunodeficiency is an immunodeficiency disorder characterized by a low level of
antibodies. Patients with this disease are subject to
recurring infections.
GALE ENCYCLOPEDIA OF MEDICINE

As is true of most immunodeficiency disorders, one
of the first signs that the patient has the condition is
recurrent infections. Patients with common variable
immunodeficiency are subject to recurrent infections,
especially those caused by microbes that don’t normally
cause disease in normal persons. The main diagnostic
test that distinguishes common variable immunodeficiency from other immunodeficiency diseases is the low
antibody level despite the normal number of B cells.
Antibody levels are tested in the serum by a procedure
called electrophoresis. This procedure both quantifies
959

Common variable immunodeficiency

Description

KEY TERMS

Complement deficiencies

the amount of antibody present and identifies the various classes of antibodies. The main class of antibody
for fighting infectious diseases is IgG.

Treatment
There is no treatment that will cure the disorder.
Treatment for common variable immunodeficiency
aims at boosting the body’s immune response and preventing or controlling infections. Immune serum,
obtained from donated blood, is given as a source of
antibodies to boost the immune response. Immune
serum is obtained from donated blood. It contains
whatever antibodies the donors had in their blood.
Consequently, it may not contain all the antibodies
that the patient needs and may lack antibodies specific
for some of the recurring infections that these patients
suffer. Antibiotics are used routinely at the first sign of
an infection to help the patient eliminate infectious
microorganisms.

Prognosis
With good medical care, people with common
variable immunodeficiency usually have a normal life
span.

Prevention
The disease itself cannot be prevented, but
patients and their families can take precautions to
prevent the recurrent infections commonly associated
with it. For example, good hygiene and nutrition are
important, as is avoiding crowds or other people who
have active infections.

Complement plays several functions in immunity.
It can poke holes in bacteria, kill bacteria that are first
targeted by antibodies, or, working with antibodies,
point out which bacteria need to be engulfed by white
blood cells. Without sufficient complement, the body
is prone to frequent infections, like pneumonia or
meningitis, or other illnesses, including autoimmune
diseases, like systemic lupus erythematosus. Since there
are more than 20 different types of complement, the
disease that results depends on the specific complement that is lacking.

Cause and symptoms
A defect in the complement system can be genetic,
but a secondary complement deficiency can also result
from ailments that involve a lot of protein loss, including serious burns, liver or kidney disease, and autoimmune diseases, like lupus. Symptoms vary depending
on the specific complement deficiency and the disease
that results. Some people remain healthy with no
symptoms at all. Others, who suffer from frequent
infections, may develop a high fever, diarrhea, headaches with a stiff neck, or a cough with chest pain. If an
autoimmune disease develops, like lupus, the person
may lose weight, suffer from a rash, and have joint
pain. Other symptoms of complement deficiency
diseases (like hereditary angioedema, paroxysmal
nocturnal hemoglobinuria, or leukocyte adhesion
deficiency syndrome) include abdominal and back
pain, skin infections, edema or swelling of the face
and red bumps on the skin.

Diagnosis

Resources
BOOKS

Abbas, Abul K., Andrew H. Lichtman, and Jordan S. Pober.
Cellular and Molecular Immunology. 3rd ed.
Philadelphia: W. B. Saunders Co., 1997.

John T. Lohr, PhD

I Complement deficiencies
Definition
Complement deficiencies are a group of disorders
in which there is a reduced level of specific proteins,
complement, involved in proper immune functioning.
960

Description

There are blood tests which determine the activity
of the complement system. The two most common
screening tests, CH50 and APH50, tell the physician
which group of complement components have a
defect. More specific blood tests for the individual
complement components (e.g., C3 or C4 complement)
are then performed. Other specialized blood tests,
including C1 esterase level, Ham test, and a white
blood count, may also be performed.

Treatment
There is no way to treat the actual complement
deficiency. However, antibiotics are used to treat infections and vaccinations are given to reduce the risk of
disease. Often, the person is vaccinated against infections that include influenza, pneumonia, and meningitis. In some cases, (e.g. a specific disease called
GALE ENCYCLOPEDIA OF MEDICINE

Autoimmune diseases—A group of diseases, like
rheumatoid arthritis and systemic lupus erythematosus, in which immune cells turn on the body,
attacking various tissues and organs.
Hereditary angioedema—A complement deficiency characterized by lymphatic vessel
blockages that cause temporary swelling (edema)
of areas of the skin, mucous membranes, and,
sometimes, internal organs.
Leukocyte adhesion deficiency syndrome—A
complement deficiency syndrome characterized
by recurrent infections of the skin, mucous membranes, and gastrointestinal tract and the absence of
pus formation. This disorder is sometimes apparent
at birth when separation of the umbilical cord takes
longer than normal.
Meningitis—An inflammation of the lining surrounding the brain and spinal cord.
Paroxysmal nocturnal hemoglobinuria (PNH)—A
rare complement disorder characterized by episodes of red blood cell destruction (hemolysis)
and blood in the urine (hemoglobinuria) that is
worse at night.
Systemic lupus erythematosus—An autoimmune
disease in which the immune system attacks the
body’s connective tissue. A butterfly-shaped facial
rash is characteristic.
White blood cells—Cells that are key in immune
defense. There are various types, including those
that engulf and kill invading bacteria.

that have a high mortality rate. In those cases, death
may occur within 10 years after diagnosis.

Prevention
There is currently no way to prevent complement
deficiencies.
Resources
ORGANIZATIONS

Immune Deficiency Foundation. 25 W. Chesapeake Ave.,
Suite 206, Towson, MD 21204. (800) 296-4433.
<http://www.primaryimmune.org>.
OTHER

‘‘The Clinical Presentation of the Primary
Immunodeficiency Diseases.’’ International Patient
Organization for Patients with Primary
Immunodeficiences. <http://www.ipopi.org>.

Jeanine Barone, Physiologist

Complete blood count see Blood count

I Computed tomography scans
Definition
Computed tomography (CT) scans are completed
with the use of a 360-degree x-ray beam and computer
production of images. These scans allow for crosssectional views of body organs and tissues.

Purpose
paroxysmal nocturnal hemoglobinuria [NH]) a bone
marrow transplant may be recommended.

Alternative treatment
There is no alternative treatment for complement
problems.

CT scans are used to image a wide variety of body
structures and internal organs. Since the 1990s, CT
equipment has become more affordable and available.
In some diagnoses, CT scans have become the first
imaging exam of choice. Because the computerized
image is so sharp, focused, and three-dimensional,
many tissues can be better differentiated than on standard x rays. Common CT indications include:


Sinus studies. The CT scan can show details of a
sinusitis, and bone fractures. Physicians may order
CT of the sinuses to provide an accurate map for
surgery.



Brain studies. Brain scans can detect hematomas,
tumors, and strokes. The introduction of CT scanning, especially spiral CT, has helped reduce the need
for more invasive procedures such as cerebral
angiography.

Prognosis
Since complement deficiencies include a wide
range of disorders, the prognoses can also vary widely.
Some patients remain healthy their entire life. Others
are hospitalized frequently because of infections
which, if not properly treated, can be fatal. Those
with autoimmune diseases could have a normal life
expectancy. There are some complement deficiencies,
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961

Computed tomography scans

KEY TERMS

Computed tomography scans



Body scans. CT scans of the body will often be used
to observe abdominal organs, such as the liver, kidneys, adrenal glands, spleen, and lymph nodes, and
extremities.



Aorta scans. CT scans can focus on the thoracic or
abdominal aorta to locate aneurysms and other possible aortic diseases.



Chest scans. CT scans of the chest are useful in
distinguishing tumors and in detailing accumulation
of fluid in chest infections.

Precautions
Pregnant women or those who could possibly be
pregnant should not have a CT scan unless the diagnostic benefits outweigh the risks. Pregnant patients
should particularly avoid full body or abdominal
scans. If the exam is necessary for obstetrics purposes,
technologists are instructed not to repeat films if there
are errors. Pregnant patients receiving CT or any x-ray
exam away from the abdominal area may be protected
by a lead apron; most radiation, known as scatter,
travels through the body and is not blocked by the
apron.
Contrast agents are often used in CT exams and
the use of these agents should be discussed with the
medical professional prior to the procedure. Patients
should be asked to sign a consent form concerning
the administration of contrast. One of the common
contrast agents, iodine, can cause allergic reactions.
Patients who are known to be allergic to iodine
(or shellfish) should inform the physician prior to the
CT scan.

Description
Computed tomography, also called CT scan,
CAT scan, or computerized axial tomography, is a
combination of focused x-ray beams and computerized production of an image. Introduced in the early
1970s, this radiologic procedure has advanced rapidly
and is now widely used, sometimes in the place of
standard x rays.
CT equipment
A CT scan may be performed in a hospital or
outpatient imaging center. Although the equipment
looks large and intimidating, it is very sophisticated
and fairly comfortable. The patient is asked to lie on a
gantry, or narrow table, that slides into the center of
the scanner. The scanner looks like a doughnut and is
round in the middle, which allows the x-ray beam to
962

rotate around the patient. The scanner section may
also be tilted slightly to allow for certain cross-sectional angles.
CT procedure
The patient will feel the gantry move very slightly
as the precise adjustments for each sectional image are
made. A technologist watches the procedure from a
window and views the images on a computer screen.
It is essential that the patient lie very still during
the procedure to prevent motion blurring. In some
studies, such as chest CTs, the patient will be asked
to hold his or her breath during image capture.
Following the procedure, films of the images are
usually printed for the radiologist and referring physician to review. A radiologist can also interpret CT
exams on a special computer screen. The procedure
time will vary in length depending on the area being
imaged. Average study times are from 30 to 60 minutes. Some patients may be concerned about claustrophobia, but the width of the ‘‘doughnut’’ portion of
the scanner is such that many patients can be reassured
of openness.
The CT image
While traditional x rays image organs in two
dimensions, with the possibility that organs in the
front of the body are superimposed over those in the
back, CT scans allow for a more three-dimensional
effect. Some have compared CT images to slices in a
loaf of bread. Precise sections of the body can be
located and imaged as cross-sectional views. The
screen before the technologist shows a computer’s
analysis of each section detected by the x-ray beam.
Thus, various densities of tissue can be easily
distinguished.
Contrast agents
Contrast agents are often used in CT exams and in
other radiology procedures to illuminate certain
details of anatomy which may not be easily seen.
Some contrasts are natural, such as air or water.
Other times, a water-based contrast agent is administered for specific diagnostic purposes. Barium sulfate
is commonly used in gastroenterology procedures.
The patient may drink this contrast, or receive it in
an enema. Oral and rectal contrast are usually given
when examining the abdomen or cells, and not given
when scanning the brain or chest. Iodine is the most
widely used intravenous contrast agent and is given
through an intravenous needle.
GALE ENCYCLOPEDIA OF MEDICINE

Colorized CT scan of human abdomen—aorta is dead center/
red. (Photo Researchers. Reproduced by permission.)

Some facilities will have both spiral and conventional CT available. Although spiral is more advantageous for many applications, conventional CT is
still a superior and precise method for imaging many
tissues and structures. The physician will evaluate
which type of CT works best for the specific exam
purpose.

Preparation
If a contrast medium is administered, the patient
may be asked to fast from about four to six hours prior
to the procedure. Patients will usually be given a gown
(like a typical hospital gown) to be worn during the
procedure. All metal and jewelry should be removed to
avoid artifacts on the film.

Aftercare

CT scan of facial sinuses. (Pascal Goetgheluck. Photo
Researchers. Reproduced by permission.)

If contrast agents are used in the CT exam, these
will be administered several minutes before the study
begins. Abdominal CT patients may be asked to
drink a contrast medium. Some patients may experience a salty taste, flushing of the face, warmth or
slight nausea, or hives from an intravenous contrast
injection. Technologists and radiologists have
equipment and training to help patients through
these minor reactions and to handle more severe
reactions. Severe reactions to contrast are rare, but
do occur.

No aftercare is generally required following a CT
scan. Immediately following the exam, the technologist will continue to watch the patient for possible
adverse contrast reactions. Patients are instructed to
advise the technologist of any symptoms, particularly
respiratory difficulty. The site of contrast injection will
be bandaged and may feel tender following the exam.
Hives may develop later and usually do not require
treatment.

Risks
Radiation exposure from a CT scan is similar to,
though higher than, that of a conventional x ray.
Although this is a risk to pregnant women, the exposure to other adults is minimal and should produce no
effects. Although severe contrast reactions are rare,
they are a risk of many CT procedures.

Spiral CT
Spiral CT, also called helical CT, is a newer
version of CT scanning which is continuous in
motion and allows for three-dimensional recreation
of images. For example, traditional CT allows the
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Normal findings on a CT exam show bone, the
most dense tissue, as white areas. Tissues and fat will
show as various shades of gray, and fluids will be gray
963

Computed tomography scans

technologist to take slices at very small and precise
intervals one after the other. Spiral CT allows for a
continuous flow of images, without stopping the
scanner to move to the next image slice. A major
advantage of spiral CT is the ability to reconstruct
images anywhere along the length of the study area.
The procedure also speeds up the imaging process,
meaning less time for the patient to lie still. The
ability to image contrast more rapidly after it is
injected, when it is at its highest level, is another
advantage of spiral CT’s high speed.

Computed tomography scans

or black. Air will also look black. Intravenous, oral,
and rectal contrast appear as white areas. The radiologist can determine if tissues and organs appear
normal by the sensitivity of the gray shadows. In CT,
the images that can cut through a section of tissue or
organ provide three-dimensional viewing for the radiologist and referring physician.

Abnormal results
Abnormal results may show different characteristics of tissues within organs. Accumulations of blood
or other fluids where they do not belong may be
detected. Radiologists can differentiate among types
of tumors throughout the body by viewing details of
their makeup.
Sinus studies
The increasing availability and lowered cost of CT
scanning has led to its increased use in sinus studies,
either as a replacement for a sinus x ray or as a followup to an abnormal sinus radiograph. The sensitivity of
CT allows for location of areas of sinus infection,
particularly chronic infection. CT scans can show the
extent and location of tiny fractures to the sinus and
nasal bones. Foreign bodies in the sinus and nasal area
are also easily detected by CT. CT imaging of the
sinuses is important in evaluating trauma or disease
of the sphenoid bone (the wedge shaped bone at the
base of the skull). Sinus tumors will show as shades of
gray indicating the difference in their density from that
of normal tissues in the area.

KEY TERMS
Aneurysm—The bulging of the blood vessel wall.
Aortic aneurysms are the most dangerous.
Aneurysms can break and cause bleeding.
Contrast (agent, medium)—A substance injected
into the body that illuminates certain structures
that would otherwise be hard to see on the radiograph (film).
Gantry—A name for the couch or table used in a
CT scan. The patient lies on the gantry while it
slides into the x-ray scanner portion.
Hematoma—A collection of blood that has
escaped from the vessels. It may clot and harden,
causing pain to the patient.
Hydrocephalus—A collection of fluid on or around
the brain. The pressure from the spinal fluid causes
the ventricles to widen.
Metastasis—Secondary cancer, or cancer that has
spread from one body organ or tissue to another.
Radiologist—A medical doctor specially trained in
radiology (x ray) interpretation and its use in the
diagnosis of disease and injury.
Spiral CT—Also referred to as helical CT, this
method allows for continuous 360-degree x-ray
image capture.
Thoracic—Refers to the chest area. The thorax runs
between the abdomen and neck and is encased in
the ribs.

Brain studies
The precise differences in density allowed by CT
scan can clearly show tumors, strokes, or lesions in the
brain area as altered densities. These lighter or darker
areas on the image may indicate a tumor or hematoma
within the brain and skull area. Different types of
tumors can be identified by the presence of edema, by
the tissue’s density, or by studying blood vessel location and activity. The speed and convenience of CT
often allows for detection of hemorrhage before symptoms even occur. Congenital abnormalities in children, such as hydrocephalus, may also be confirmed
with CT. Hydrocephalus is suggested by enlargement
of the fluid structures called ventricles of the brain.
Body scans
The body scan can identify abnormal body structures and organs. Throughout the body, a CT may
indicate tumors or cysts, enlarged lymph nodes,
964

abnormal collections of fluids, blood or fat, and
metastasis of cancer. Tumors resulting from metastasis are different in makeup than primary tumors, or
those that originate in the location of study. Fractures
or damage to soft tissues and ligaments will be more
easily seen on the sensitive images produced by CT
scanning, though CT is not usually done for these.
Liver conditions, such as cirrhosis or abscessed or
fatty liver, may be observed on the body scan.
CT of the aorta
CT provides the ability to see and measure the
thickness of the aortal wall, which is very helpful in
diagnosing aortic aneurysms. The use of contrast will
help see details within the aorta. In addition, density
can identify calcification, and this helps differentiate
between acute and chronic problems. An abnormal
CT scan may indicate signs of aortic clots. Aortic
GALE ENCYCLOPEDIA OF MEDICINE

Chest scans
In addition to those findings that may indicate
aortic aneurysms, chest CT studies can show other
problems in the heart and lungs, and distinguish
between an aortic aneurysm and a tumor adjacent to
the aorta. The computer will not only show differences
between air, water, tissues, and bone, but will also
assign numerical values to the various densities.
Coin-sized lesions in the lungs may be indicative of
tuberculosis or tumors. CT will help distinguish among
the two. Enlarged lymph nodes in the chest area may
indicate Hodgkin’s disease. Spiral CT is particularly
effective at identifying pulmonary emboli (clots in the
lung’s blood vessels).
Resources
PERIODICALS

Papatheofanis, Frank J. ‘‘Helical CT and Pulmonary
Disease.’’ Decisions in Imaging Economics (JanuaryFebruary 1997): 61-63.
ORGANIZATIONS

American College of Radiology. 1891 Preston White Drive,
Reston, VA 22091. (800) 227-5463. <http://
www.acr.org>.

Teresa Odle

Computerized axial tomography see
Computed tomography scans

I Concussion
Definition
Concussion is a trauma-induced change in mental
status, with confusion and amnesia, and with or without a brief loss of consciousness.

Description
A concussion occurs when the head hits or is hit
by an object, or when the brain is jarred against the
skull, with sufficient force to cause temporary loss of
function in the higher centers of the brain. The
injured person may remain conscious or lose consciousness briefly, and is disoriented for some minutes after the blow. According to the Centers for
Disease Control and Prevention, approximately
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300,000 people sustain mild to moderate sportsrelated brain injuries each year, most of them young
men between 16 and 25.
While concussion usually resolves on its own
without lasting effect, it can set the stage for a much
more serious condition. ‘‘Second impact syndrome’’
occurs when a person with a concussion, even a very
mild one, suffers a second blow before fully recovering
from the first. The brain swelling and increased intracranial pressure that can result is potentially fatal.
More than 20 such cases have been reported since the
syndrome was first described in 1984.

Causes and symptoms
Causes
Most concussions are caused by motor vehicle
accidents and sports injuries. In motor vehicle accidents, concussion can occur without an actual blow
to the head. Instead, concussion occurs because the
skull suddenly decelerates or stops, which causes
the brain to be jarred against the skull. Contact
sports, especially football, hockey, and boxing, are
among those most likely to lead to concussion.
Other significant causes include falls, collisions, or
blows due to bicycling, horseback riding, skiing, and
soccer.
The risk of concussion from football is extremely
high, especially at the high school level. Studies show
that approximately one in five players suffer concussion or more serious brain injury during their brief
high-school careers. The rate at the collegiate level is
approximately one in 20. Rates for hockey players
are not known as certainly, but are believed to be
similar.
Concussion and lasting brain damage is an especially significant risk for boxers, since the goal of the
sport is, in fact, to deliver a concussion to the opponent. For this reason, the American Academy of
Neurology has called for a ban on boxing. Repeated
concussions over months or years can cause cumulative head injury. The cumulative brain injuries suffered
by most boxers can lead to permanent brain damage.
Multiple blows to the head can cause ‘‘punch-drunk’’
syndrome or dementia pugilistica, as evidenced by
Muhammaed Ali, whose parkinsonism is a result of
his career in the ring.
Young children are likely to suffer concussions
from falls or collisions on the playground or around
the home. Child abuse is, unfortunately, another common cause of concussion.
965

Concussion

rupture is suggested by signs such as a hematoma
around the aorta or the escape of blood from its cavity.

Concussion

Symptoms
Symptoms of concussion include:


headache



disorientation as to time, date, or place



confusion



dizziness



vacant stare or confused expression



incoherent or incomprehensible speech



incoordination or weakness



amnesia for the events immediately preceding the
blow



nausea or vomiting



double vision



ringing in the ears

These symptoms may last from several minutes to
several hours. More severe or longer-lasting symptoms may indicate more severe brain injury. The person with a concussion may or may not lose
consciousness from the blow; if so, it will be for several
minutes at the most. More prolonged unconsciousness
indicates more severe brain injury.
The severity of concussion is graded on a threepoint scale, used as a basis for treatment decisions.


Grade 1: no loss of consciousness, transient confusion, and other symptoms that resolve within
15 minutes.



Grade 2: no loss of consciousness, transient confusion, and other symptoms that require more than
15 minutes to resolve.



Grade 3: loss of consciousness for any period.

Days or weeks after the accident, the person may
show signs of:


headache



poor attention and concentration



memory difficulties



anxiety



depression



sleep disturbances



light and noise intolerance

The occurrence of such symptoms is called ‘‘postconcussion syndrome.’’
966

Diagnosis
It is very important for those attending a person
with concussion to pay close attention to the person’s
symptoms and progression immediately after the accident. The duration of unconsciousness and degree of
confusion are very important indicators of the severity
of the injury and help guide the diagnostic process and
treatment decisions.
A doctor, nurse, or emergency medical technician
may make an immediate assessment based on the
severity of the symptoms; a neurologic exam of the
pupils, coordination, and sensation; and brief tests of
orientation, memory, and concentration. Those with
very mild concussions may not need to be hospitalized
or have expensive diagnostic tests. Questionable or
more severe cases may require computed tomography
scan (CT) or magnetic resonance imaging (MRI) scans
to look for brain injury.

Treatment
The symptoms of concussion usually clear quickly
and without lasting effect, if no further injury is sustained during the healing process. Guidelines for
returning to sports activities are based on the severity
of the concussion.
A grade 1 concussion can usually be treated with
rest and continued observation alone. The person may
return to sports activities that same day, but only after
examination by a trained professional, and after all
symptoms have completely resolved. If the person
sustains a second concussion of any severity that
same day, he or she should not be allowed to continue
contact sports until he or she has been symptom-free,
during both rest and activity, for one week.
A person with a grade 2 concussion must discontinue sports activity for the day, should be evaluated
by a trained professional, and should be observed
closely throughout the day to make sure that all symptoms have completely cleared. Worsening of symptoms, or continuation of any symptoms beyond one
week, indicates the need for a CT or MRI scan. Return
to contact sports should only occur after one week
with no symptoms, both at rest and during activity,
and following examination by a physician. Following
a second grade 2 concussion, the person should remain
symptom-free for two weeks before resuming contact
sports.
A person with a grade 3 concussion (involving any
loss of consciousness, no matter how brief) should be
examined by a medical professional either on the scene
or in an emergency room. More severe symptoms may
GALE ENCYCLOPEDIA OF MEDICINE

Amnesia—A loss of memory that may be caused by
brain injury, such as concussion.
Parkinsonism—A neurological disorder that
includes a fine tremor, muscular weakness and
rigidity, and an altered way of walking.

warrant a CT or MRI scan, along with a thorough
neurological and physical exam. The person should be
hospitalized if any abnormalities are found or if confusion persists. Prolonged unconsciousness and worsening symptoms require urgent neurosurgical
evaluation or transfer to a trauma center. Following
discharge from professional care, the patient is closely
monitored for neurological symptoms which may
arise or worsen. If headaches or other symptoms worsen or last longer than one week, a CT or MRI scan
should be performed. Contact sports are avoided for
one week following unconsciousness of only seconds,
and for two weeks for unconsciousness of a minute or
more. A person receiving a second grade 3 concussion
should avoid contact sports for at least a month after
all symptoms have cleared, and then only with the
approval of a physician. If signs of brain swelling or
bleeding are seen on a CT or MRI scan, the athlete
should not return to the sport for the rest of the
season, or even indefinitely.
For someone who has sustained a concussion of
any severity, it is critically important that he or she
avoid the possibility of another blow to the head until
well after all symptoms have cleared to prevent second-impact syndrome. The guidelines above are
designed to minimize the risk of this syndrome.

Prognosis
Concussion usually leaves no lasting neurological
problems. Nonetheless, symptoms of post-concussion
syndrome may last for weeks or even months.
Studies of concussion in contact sports have
shown that the risk of sustaining a second concussion
is even greater than it was for the first if the person
continues to engage in the sport.

Prevention
Many cases of concussion can be prevented by
using appropriate protective equipment. This includes
seat belts and air bags in automobiles, and helmets in
GALE ENCYCLOPEDIA OF MEDICINE

all contact sports. Helmets should also be worn when
bicycling, skiing, or horseback riding. Soccer players
should avoid heading the ball when it is kicked at high
velocity from close range. Playground equipment
should be underlaid with soft material, either sand or
special matting.
The value of high-contact sports such as boxing,
football, or hockey should be weighed against the high
risk of brain injury during a young person’s participation in the sport. Steering a child’s general enthusiasm
for sports into activities less apt to produce head
impacts may reduce the likelihood of brain injury.
Resources
BOOKS

Evans, R. Neurology and Trauma. W. B. Saunders Co., 1996.
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave.,
St. Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.

Richard Robinson

I Condom
Definition
Male condoms are thin sheaths of latex (rubber),
polyurethane (plastic), or animal tissue that are rolled
onto an erect penis immediately prior to intercourse.
They are commonly called ‘‘safes’’ or ‘‘rubbers.’’
Female condoms are made of polyurethane and are
inserted into the vaginal canal before sexual relations.
The open end covers the outside of the vagina, and the
closed ring fits over the cervix (opening into the
uterus). Both types of condoms collect the male
semen at ejaculation, acting as a barrier to fertilization. Condoms also perform as barriers to the
exchange of bodily fluids and are subsequently an
important tool in the prevention of sexually transmitted diseases (STDs).

Purpose
Both male and female condoms are used to prevent pregnancy and to protect against STDs such as
human immunodeficiency virus (HIV), gonorrhea,
chlamydia, and syphilis. To accomplish these goals,
the condom must be applied and removed correctly.
967

Condom

KEY TERMS

Condom

Precautions
Male and female condoms should not be used
together as there is a risk that one of them may come
off. The male condom should not be snug on the tip of
the penis. A space of about 0.5 in should be left at the
end to avoid the possibility of it breaking during sexual intercourse. The penis must be withdrawn quickly
after ejaculation to prevent the condom from falling
off as the penis softens. The condom should therefore
always be removed while the penis is still erect to
prevent the sperm from spilling into the vagina.

Penis

Description
Male condoms made from animal tissue and linen
have been in use for centuries. Latex condoms were
introduced in the late 1800s and gained immediate
popularity because they were inexpensive and effective. At that time, they were primarily used to protect
against STDs. A common complaint made by many
consumers is that condoms reduce penis sensitivity
and impair orgasm. Both men and women may
develop allergies to the latex. Consumer interest in
female condoms has been slight.
Male condoms may be purchased lubricated,
ribbed, or treated with spermicide (a chemical that
kills sperm). To be effective, condoms must be
removed carefully so as not to ‘‘spill’’ the contents
into the vaginal canal. Condoms that leak or break
do not provide protection against pregnancy or
disease.
If used correctly, male condoms have an effectiveness rate of about 90% for preventing pregnancy, but
this rate can be increased to about 99% if used with a
spermicide. (Several types of spermicides are available;
they can be purchased in the form of contraceptive
creams and jellies, foams, or films.) Benefits associated
with this type of contraceptive device include easy
availability (no prescription is required), convenience
of use, and lack of serious side effects. The primary
disadvantage is that sexual activity must be interrupted in order to put the condom on.
Female condoms, when used correctly and at
every instance of intercourse, were shown to prevent
pregnancy in over 95% of women surveyed over the
course of six months. When used inconsistently, the
female condom was shown to have a failure rate of
21% in the same study. One benefit of the female
condom is that it may be inserted immediately before
sexual intercourse or up to eight hours prior, so that
sexual activity does not need to be interrupted for its
insertion. One study performed by a manufacturer of
968

Condom

A condom is most effective when it is placed on the penis
correctly without trapping air between the penis and the
condom. (Illustration by Argosy, Inc.)

KEY TERMS
Ejaculate—To expel semen.
Semen—The thick whitish liquid released from the
penis during sexual intercourse. It contains sperm
and other secretions.
Sperm or spermatozoa—The part of the semen that
is generative—can cause fertilization of the female
ovum.
Spermicide—An agent that is destructive to sperm.
Vagina—The genital canal in the female, leading
from the vulva to the uterus.

the female condom indicated that 50–75% of couples
in numerous countries found the barrier acceptable
for use.
Condoms provide better protection against STDs
than any other contraceptive method. One study conducted in the 1990s indicated that out of 123 couples
with one HIV-positive partner, not one healthy individual contracted the disease when condoms were used
with every instance of sexual intercourse. A similar
GALE ENCYCLOPEDIA OF MEDICINE

Before purchasing a condom, check the expiration date. Prior to use, examine the condom for holes.
If a lubricant is going to be used, it should be water
soluble because petroleum jellies, such as Vaseline,
and other oil based lubricants can weaken latex. It is
also important to note that condoms made from
animal tissue or plastic are not recommended as a
protection against STDs.

stealing, truancy, and running away from home.
They often begin using and abusing drugs and alcohol,
and having sex at an early age. Irritability, temper
tantrums, and low self-esteem are common personality traits of children with CD.

Causes and symptoms
There are two sub-types of CD, one beginning in
childhood and the other in adolescence. There is no
known cause. Researchers and physicians suggest that
this disease may be caused by the following:


poor parent-child relationships



dysfunctional families



drug abuse



physical abuse

Resources



poor relationships with other children

OTHER



cognitive problems leading to school failures

‘‘The Condom.’’ Sexual Health InfoCenter. <http://
www.sexhealth.org/infocenter/GuideSS/
condoms.htm>.
‘‘Condoms.’’ Planned Parenthood Page. <http://
www.plannedparenthood.org/condoms/index.html>.
‘‘The Female Condom.’’ Fronske Health Center. 2001.
<http://www.nau.edu/fronske/fcondom.html>.
‘‘Spermicides, Condoms and Other Barrier Methods.’’
Epigee Birth Control Guide. <http://epigee.netministries.org/guide/barrier.html>.



brain damage



biological defects

Stephanie Dionne

I Conduct disorder
Definition
Conduct disorder (CD) is a behavioral and emotional disorder of childhood and adolescence.
Children with conduct disorder act inappropriately,
infringe on the rights of others, and violate the behavioral expectations of others.

Description
CD is present in approximately 9% of boys and
2–9% of girls under the age of 18. Children with conduct disorder act out aggressively and express anger
inappropriately. They engage in a variety of antisocial
and destructive acts, including violence towards people and animals, destruction of property, lying,
GALE ENCYCLOPEDIA OF MEDICINE

Difficulty in school is an early sign of potential
conduct disorder problems. While the patient’s IQ
tends to be in the normal range, they can have trouble
with verbal and abstract reasoning skills and may lag
behind their classmates, and consequently, feel as if
they don’t ‘‘fit in.’’ The frustration and loss of selfesteem resulting from this academic and social inadequacy can trigger the development of CD.
A dysfunctional home environment can be
another major contributor to CD. An emotionally,
physically, or sexually abusive home environment, a
family history of antisocial personality disorder, or
parental substance abuse can damage a child’s perceptions of himself and put him on a path toward negative
behavior. Other less obvious environmental factors
can also play a part in the development of conduct
disorder. Long-term studies have shown that maternal
smoking during pregnancy may be linked to the development of CD in boys. Animal and human studies
point out that nicotine can have undesirable effects
on babies. These include altered structure and function of their nervous systems, learning deficits, and
behavioral problems. In a study of 177 boys ages
seven to 12 years, those with mothers who smoked
over one-half a package of cigarettes daily while pregnant were more apt to have a CD than those with
mothers who did not smoke.
Other conditions that may cause or co-exist with
CD include head injury, substance abuse disorder,
major depressive disorder, and attention deficit
969

Conduct disorder

1993 study showed that out of 171 couples with one
HIV-positive partner, all but two individuals were
protected against HIV transmission with condom
use. In addition to HIV, condoms provide effective
transmission against gonorrhea, chlamydia, syphilis,
chancroid, and trichomoniasis. A measure of protection is also provided against hepatitis B virus (HBV),
human papillomavirus (HPV), and herpes simplex
virus (HSV).

Conduct disorder

hyperactivity disorder (ADHD). Thirty to fifty percent
of children diagnosed with ADHD, a disorder characterized by a persistent pattern of inattention and/or
hyperactivity, also have CD.
CD is defined as a repetitive behavioral pattern of
violating the rights of others or societal norms. Three
of the following criteria, or symptoms, are required
over the previous 12 months for a diagnosis of CD
(one of the three must have occurred in the past six
months):


bullies, threatens, or intimidates others



picks fights



has used a dangerous weapon



has been physically cruel to people



has been physically cruel to animals



has stolen while confronting a victim (for example,
mugging or extortion)



has forced someone into sexual activity



has deliberately set a fire with the intention of
causing damage



has deliberately destroyed property of others



has broken into someone else’s house or car



frequently lies to get something or to avoid
obligations



has stolen without confronting a victim or breaking
and entering (e.g., shoplifting or forgery)



stays out at night; breaks curfew (beginning before
13 years of age)



has run away from home overnight at least twice (or
once for a lengthy period)



is often truant from school (beginning before
13 years of age)

Diagnosis
CD is diagnosed and treated by a number of social
workers, school counselors, psychiatrists, and psychologists. Genuine diagnosis may require psychiatric
expertise to rule out such conditions as bipolar disorder
or ADHD. A comprehensive evaluation of the child
should ideally include interviews with the child and
parents, a full social and medical history, a cognitive
evaluation, and a psychiatric exam. One or more clinical inventories or scales may be used to assess the
child for conduct disorder—including the Youth
Self-Report, the Overt Aggression Scale (OAS),
Behavioral Assessment System for Children (BASC),
Child Behavior Checklist (CBCL), and Diagnostic
970

KEY TERMS
ADHD—Attention deficit hyperactivity disorder; a
disorder characterized by a persistent pattern of
inattention and/or hyperactivity.
Major depressive disorder—A mood disorder characterized by profound feelings of sadness or
despair.

Interview Schedule for Children (DISC). The tests
are verbal and/or written and are administered in
both hospital and outpatient settings.

Treatment
Treating conduct disorder requires an approach
that addresses both the child and his environment.
Behavioral therapy and psychotherapy can help a
child with CD to control his anger and develop new
coping skills. Family group therapy may also be effective in some cases. Parents should be counseled on how
to set appropriate limits with their child and be consistent and realistic when disciplining. If an abusive
home life is at the root of the conduct problem, every
effort should be made to move the child into a more
supportive environment. Parent training programs are
increasing in number.
For children with coexisting ADHD, substance
abuse, depression, or learning disorders, treating
these conditions first is preferred, and may result in a
significant improvement to the CD condition. In all
cases of CD, treatment should begin when symptoms
first appear. Recent studies have shown Ritalin to be a
useful drug for both ADHD and CD.
When aggressive behavior is severe, mood stabilizing medication, including lithium (Cibalith-S,
Eskalith, Lithane, Lithobid, Lithonate, Lithotabs),
carbamazepine (Tegretol, Atretol), and propranolol
(Inderal), may be an appropriate option for treating
the aggressive symptoms. However, placing the child
into a structured setting or treatment program such as
a psychiatric hospital may be just as beneficial for
easing aggression as medication.

Prognosis
The prognosis for children with CD is not bright.
Follow-up studies of conduct disordered children have
shown a high incidence of antisocial personality
disorder, affective illnesses, and chronic criminal
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
A supportive, nurturing, and structured home
environment is believed to be the best defense against
CD. Children with learning disabilities and/or difficulties in school should get immediate and appropriate
academic assistance. Addressing these problems when
they first appear helps to prevent the frustration and
low self-esteem that may lead to CD later on.
Resources
BOOKS

Diagnostic and Statistical Manual of Mental Disorders. 4th
ed. Washington, DC: American Psychiatric
Association, 2000.
ORGANIZATIONS

and normal internal reproductive tract structures.
Males have normal genitals at birth. CAH causes
abnormal growth for both sexes; patients will be tall
as children and short as adults. Females develop male
characteristics, and males experience premature sexual
development.
In its most severe form, called salt-wasting CAH,
a life-threatening adrenal crisis can occur if the disorder is untreated. Adrenal crisis can cause dehydration,
shock, and death within 14 days of birth. There is also a
mild form of CAH that occurs later in childhood or
young adult life in which patients have partial enzyme
deficiency.
CAH, a genetic disorder, is the most common
adrenal gland disorder in infants and children, occurring in one in 10,000 total births worldwide. It affects
both females and males. It is also called adrenogenital
syndrome.

Causes and symptoms

American Academy of Child and Adolescent Psychiatry
(AACAP). 3615 Wisconsin Ave. NW, Washington, DC
20016. (202) 966-7300. <http://www.aacap.org>.

Paula Anne Ford-Martin

Conductive hearing loss see Hearing loss
Condylomata acuminata see Genital warts
Cone biopsy see Cervical conization

adrenal
I Congenital
hyperplasia
Definition
CAH is a genetic disorder characterized by a deficiency in the hormones cortisol and aldosterone and
an over-production of the hormone androgen, which
is present at birth and affects sexual development.

Description
Congenital adrenal hyperplasia (CAH) is a form
of adrenal insufficiency in which the enzyme that
produces two important adrenal steroid hormones,
cortisol and aldosterone, is deficient. Because cortisol
production is impeded, the adrenal gland instead
overproduces androgens (male steroid hormones).
Females with CAH are born with an enlarged clitoris
GALE ENCYCLOPEDIA OF MEDICINE

CAH is an inherited disorder. It is a recessive disease, which means that a child must inherit one copy of
the defective gene from each parent who is a carrier;
when two carriers have children, each pregnancy carries
a 25% risk of producing an affected child.
In females, CAH produces an enlarged clitoris at
birth and masculinization of features as the child
grows, such as deepening of the voice, facial hair,
and failure to menstruate or abnormal periods at puberty. Females with severe CAH may be mistaken for
males at birth. In males, the genitals are normal at
birth, but the child becomes muscular, the penis
enlarges, pubic hair appears, and the voice deepens
long before normal puberty, sometimes as early as
two to three years of age.
In the severe salt-wasting form of CAH, newborns
may develop symptoms shortly after birth, including
vomiting, dehydration, electrolyte (a compound such
as sodium or calcium that separates to form ions when
dissolved in water) changes, and cardiac arrhythmia.
In the mild form of CAH, which occurs in late
childhood or early adulthood, symptoms include premature development of pubic hair, irregular menstrual
periods, unwanted body hair, or severe acne.
However, sometimes there are no symptoms.

Diagnosis
CAH is diagnosed by a careful examination of the
genitals and blood and urine tests that measure the
hormones produced by the adrenal gland. A number
971

Congenital adrenal hyperplasia

behavior later in life. However, proper treatment of
co-existing disorders, early identification and intervention, and long-term support may improve the outlook significantly.

Congenital adrenal hyperplasia

KEY TERMS
Adrenal glands—The two endocrine glands
located above the kidney that secrete hormones
and epinephrine.
Aldosterone—A hormone secreted by the adrenal
glands that is important for maintaining salt and
water balance in the body.
Adrenal cortical hyperplasia. The adrenal on the right is normal, that on the left shows hyperplasia. (Photo Researchers,
Inc. Reproduced by permission.)

of states in the United States perform a hormonal test
(a heel prick blood test) for CAH and other inherited
diseases within a few days of birth. In questionable
cases, genetic testing can provide a definitive diagnosis. For some forms of CAH, prenatal diagnosis is
possible through chronic villus sampling in the first
trimester and by measuring certain hormones in the
amniotic fluid during the second trimester.

Androgens—Steroid
masculinization.

hormones

that

cause

Congenital—Present at birth.
Cortisol—A steroid hormone secreted by the adrenal cortex that is important for maintenance of
body fluids, electrolytes, and blood sugar levels.
Hormone—A chemical messenger produced by
the endocrine glands or certain other cells.
Hormones are usually carried in the blood stream
and regulate some metabolic activities.
Steroids—Hormones, including aldosterone, cortisol, and androgens, derived from cholesterol that
share a four-ring structure.

Treatment
The goal of treatment for CAH is to return the
androgen levels to normal. This is usually accomplished through drug therapy, although surgery is an
alternative. Lifelong treatment is required.
Drug therapy consists of a cortisol-like steroid medication called a glucocorticoid. Oral hydrocortisone is
prescribed for children, and prednisone or dexamethasone is prescribed for older patients. For patients with
salt-wasting CAH, fludrocortisone, which acts like
aldosterone (the missing hormone), is also prescribed.
Infants and small children may also receive salt tablets,
while older patients are told to eat salty foods. Medical
therapy achieves hormonal balance most of the time, but
CAH patients can have periods of fluctuating hormonal
control that lead to increases in the dose of steroids
prescribed. Side effects of steroids include stunted
growth. Steroid therapy should not be suddenly stopped,
since adrenal insufficiency results.
Patients with CAH should see a pediatric endocrinologist frequently. The endocrinologist will assess
height, weight, and blood pressure, and order an
annual x ray of the wrist (to assess bone age), as well
as assess blood hormone levels. CAH patients with the
milder form of the disorder are usually effectively
treated with hydrocortisone or prednisone, if they
need medical treatment at all.
Females with CAH who have masculine external
genitalia require surgery to reconstruct the clitoris
972

and/or vagina. This is usually performed between the
ages of one and three.
An experimental type of drug therapy—a threedrug combination, with an androgen blocking agent
(flutamide), an aromatase inhibitor (testolactone),
and low dose hydrocortisone—is currently being
studied by physicians at the National Institutes of
Health. Preliminary results are encouraging, but it
will be many years before the safety and effectiveness
of this therapy is fully known.
Adrenalectomy, a surgical procedure to remove
the adrenal glands, is a more radical treatment for
CAH. It was widely used before the advent of steroids.
Today, it is recommended for CAH patients with little
or no enzyme activity and can be accomplished by
laparoscopy. This is a minimally invasive type of surgery done through one or more small 1 in (2.5 cm)
incisions and a laparoscope, an instrument with a
fiber-optic light containing a tube with openings for
surgical instruments. Adrenalectomy is followed by
hormone therapy, but in lower doses than CAH
patients not treated surgically receive.

Prognosis
CAH can be controlled and successfully treated in
most patients as long as they remain on drug therapy.
GALE ENCYCLOPEDIA OF MEDICINE

Prenatal therapy, in which a pregnant woman at
risk for a second CAH child is given dexamethasone to
decrease secretion of androgens by the adrenal glands
of the female fetus, has been in use for about 10 years.
This therapy is started in the first trimester when fetal
adrenal production of androgens begins, but before
prenatal diagnosis is done that would provide definitive information about the sex of the fetus and its
disease status. This means that a number of fetuses
are exposed to unnecessary steroid treatment in order
to prevent the development of male-like genitals in
female fetuses with CAH. Several hundred children
have undergone this treatment with no major adverse
effects, but its long-term risks are unknown. Since
there is very little data on the effectiveness and safety
of prenatal therapy, it should only be offered to
patients who clearly understand the risks and benefits
and who are capable of complying with strict monitoring and follow-up throughout pregnancy and after the
child is born.
Parents with a family history of CAH, including a
child who has CAH, should seek genetic counseling.
Genetic testing during pregnancy can provide information on the risk of having a child with CAH.
Resources
ORGANIZATIONS

American Academy of Pediatrics. 141 Northwest Point
Boulevard, Elk Grove Village, IL 60007-1098. (847)
434-4000.
National Adrenal Diseases Foundation. 510 Northern
Boulevard, Great Neck, NY 11021. (516) 487-4992.
<http://medhlp.netusa.net/www/nadf.htm>.
OTHER

The Johns Hopkins Children’s Center. ‘‘Congenital Adrenal
Hyperplasia Due to 21-Hydroxylase Deficiency.’’
<http://www.med.jhu.edu/pedendo/cha/
printable.html>.

Jennifer Sisk

I Congenital amputation
Definition
Congenital amputation is the absence of a fetal
limb or fetal part at birth. This condition may be the
result of the constriction of fibrous bands within the
membrane that surrounds the developing fetus
GALE ENCYCLOPEDIA OF MEDICINE

(amniotic band syndrome) or the exposure to substances known to cause birth defects (teratogenic
agents). Other factors, including genetics, may also
play a role.

Description
An estimated one in 2000 babies are born with all
or part of a limb missing, ranging from a missing part
of a finger to the absence of both arms and both legs.
Congenital amputation is the least common reason
for amputation. However, there are occasional periods in history where the number of congenital amputations increased. For example, the thalidomide
tragedy of the early 1960s occurred after pregnant
mothers in western Europe were given a tranquilizer
containing the drug. The result was a drastic increase
in the number of babies born with deformed limbs. In
this example, the birth defect usually presented itself
as very small, deformed versions of normal limbs.
More recently, birth defects as a result of radiation
exposure near the site of the Chernobyl disaster in
Russia have left numerous children with malformed
or absent limbs.

Causes and symptoms
The exact cause of congenital amputations is
unknown. However, according to the March of
Dimes, most birth defects have one or more genetic
factors and one or more environmental factors. It is
also known that most birth defects occur in the first
three months of pregnancy, when the organs of the
fetus are forming. Within these crucial first weeks,
frequently prior to when a woman is aware of the
pregnancy, the developing fetus is most susceptible to
substances that can cause birth defects (teratogens).
Exposure to teratogens can cause congenital amputation. In other cases, tight amniotic bands may constrict the developing fetus, preventing a limb from
forming properly if at all. It is estimated that this
amniotic band syndrome occurs in between one in
12,000 and one in 15,000 live births.
An infant with congenital amputation may be
missing an entire limb or just a portion of a limb.
Congenital amputation resulting in the complete
absence of a limb beyond a certain point (and leaving
a stump) is called transverse deficiency or amelia.
Longitudinal deficiencies occur when a specific part
of a limb is missing; for example, when the fibula bone
in the lower leg is missing, but the rest of the leg is
intact. Phocomelia is the condition in which only a
mid-portion of a limb is missing, as when the hands or
feet are attached directly to the trunk.
973

Congenital amputation

Prevention

Congenital amputation

Diagnosis
Many cases of congenital amputation are not
diagnosed until the baby is born. Ultrasound examinations may reveal the absence of a limb in some
developing fetuses, but routine ultrasounds may not
pick up signs of more subtle defects. However, if a
doctor suspects that the fetus is at risk for developing
a limb deficiency (for example, if the mother has been
exposed to radiation), a more detailed ultrasound
examination may be performed.

Treatment
Successful treatment of a child with congenital
amputation involves an entire medical team, including
a pediatrician, an orthopedist, a psychiatrist or psychologist, a prosthetist (an expert in making prosthetics, or artificial limbs), a social worker, and
occupational and physical therapists. The accepted
method of treatment is to fit the child early with a
functional prosthesis because this leads to normal
development and less wasting away (atrophy) of the
muscles of the limbs present. However, some parents
and physicians believe that the child should be allowed
to learn to play and perform tasks without a prosthesis, if possible. When the child is older, he or she can be
involved in the decision of whether or not to be fitted
for a prosthesis.
In the case of congenital amputation of the fingers, plastic surgery can sometimes be used to reconstruct the missing digits by transferring parts of the
great and second toes to the hand. Some defects in the
leg bones can be treated by removing the malformed
bone, grafting bone from other parts of the child’s
body, and inserting a metal rod to strengthen the
limb; this technique, however, is controversial as of
the early 2000s.
Recently, there have been cases in which physicians have detected amniotic band constriction interfering with limb development fairly early in its course.
In 1997, doctors at the Florida Institute for Fetal
Diagnosis and Therapy reported two cases in which
minimally invasive surgery freed constricting amniotic
bands and preserved the affected limbs.

Alternative treatment
Prevention of birth defects begins with building
the well-being of the mother before pregnancy.
Prenatal care should be strong and educational so
that the mother understands both her genetic risks
and her environmental risks. Several disciplines in
alternative therapy also recommend various
974

KEY TERMS
Amniotic band—An abnormal condition of fetal
development in which fibrous bands of tissue
develop out of the amniotic sac. The bands encircle
and constrict parts of the baby’s body, interfering
with normal development and sometimes causing
congenital amputation.
Prosthesis—An artificial replacement for a missing
part of the body.
Teratogen—Any substance, agent, or process that
interferes with normal prenatal development, causing the formation of one or more developmental
abnormalities of the fetus.

supplements and vitamins that may reduce the chances
of birth defects. If a surgical procedure is planned,
naturopathic and homeopathic pre- and post-surgical
therapies can speed recovery.

Prognosis
A congenital limb deficiency has a profound effect
on the life of the child and parents. However, occupational therapy can help the child learn to accomplish
many tasks. In addition, some experts believe that
early fitting of a prosthesis will enhance acceptance
of the prosthesis by the child and parents.

Prevention
Studies have suggested that a multivitamin including folic acid may reduce birth defects, including congenital abnormalities. Smoking, drinking alcohol, and
eating a poor diet while pregnant may increase the risk
of congenital abnormalities. Daily, heavy exposure to
chemicals may be dangerous while pregnant.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Musculoskeletal Abnormalities.’’ Section 19, Chapter
261 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Dobbs, M. B., M. M. Rich, J. E. Gordon, et al. ‘‘Use of an
Intramedullary Rod for Treatment of Congenital
Pseudarthrosis of the Tibia. A Long-Term Follow-Up
Study.’’ Journal of Bone and Joint Surgery, American
Volume 86-A (June 2004): 1186–1197.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

International Child Amputee Network. <http://www.ampinfo.net/childamp.htm>.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914) 4287100. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Organization for Rare Disorders (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT 068131968. (203) 744-0100 or (800) 999-6673. Fax: (203) 7982291. <http://www.rarediseases.org>.

Jeffrey P. Larson, RPT
Rebecca J. Frey, PhD

I Congenital bladder anomalies
Definition
The two most common congenital bladder
abnormalities are exstrophy and congenital diverticula. An exstrophic bladder is one that is open to the
outside and turned inside-out, so that its inside is
visible at birth, protruding from the lower abdomen.
A diverticulum is an extension of a hollow organ,
usually shaped like a pouch with a narrow opening.

Description
During fetal development, folds enclose tissues
and organs and eventually fuse at the edges to form
sealed compartments. Both in the front and the back,
folds eventually become major body structures. In the
back, the entire spinal column folds in like a pipe
wrapped in a pillow. In the front, the entire lower
urinary system is folded in.




Exstrophy of the bladder represents a failure of this
folding process to complete itself, so the organs form
with more or less of their front side missing and open
to the outside. At the same time, the front of the
pelvic bone is widely separated. The abdominal wall
is open, too. In fact, the defect often extends all the
way to the penis in the male or splits the clitoris in the
female.
A congenital bladder diverticulum represents an area
of weakness in the bladder wall through which
extrudes some of the lining of the bladder. (A small

GALE ENCYCLOPEDIA OF MEDICINE

balloon squeezed in a fist will create a diverticula-like
effect between the fingers.) Bladder diverticula may
be multiple, and they often occur at the ureterovesical junction–the entrance of the upper urinary system
into the bladder. In this location, they may cause
urine to reflux into the ureter and kidney, leading
to infection and possible kidney damage.

Causes and symptoms
As with many birth defects, the causes are not well
known. Lack of prenatal care and nutrition has been
linked to many birth defects, however beyond the
avoidance of known teratogens (anything that can
cause a birth defect), there is little prevention possible.
Exstrophy is rare, occurring in about one in 40,000
births. Diverticula are more common, but less serious.
If left untreated, the patient with bladder exstrophy will have no control over urination and is more
likely to develop bladder cancer. Diverticula, particularly if it causes urine reflux, may lead to chronic
infection and its subsequent consequences.

Diagnosis
A major consideration with congenital abnormalities is that they tend to be multiple. Further, each one
is unique in its extent and severity. Exstrophy can
involve the rectum and large bowel and coexist with
hernias. The obvious bladder exstrophy seen at birth
will prompt immediate action and a search for other
anomalies.
Diverticula are not visible and will be detected
only if they cause trouble. They are usually found in
an examination for the cause of recurring urinary
infections. X rays of the urinary system or a cystoscopy
(examination with a telescope-like instrument) will
identify them. Often, the two procedures are done
together: a urologist will perform the cystoscopy,
then a radiologist will instill a contrast agent into the
bladder and take x rays.

Treatment
Surgery is necessary and can usually produce successful results. If possible, the surgery must be done
within 48 hours of birth. Prior to surgery, the exposed
organs must be protected and all related defects identified and managed. Delay in the surgery leads to the
frequent need to divert the urine into the bowel
because the partially repaired bladder cannot control
the flow. After surgery, the likelihood of infection
requires monitoring.
975

Congenital bladder anomalies

Garcia Julve G., and G. Martinez Villen. ‘‘The Multiple
Monoblock Toe-to-Hand Transfer in Digital
Reconstruction. A Report of Ten Cases.’’ Journal of
Hand Surgery 29 (June 2004): 222–229.

Congenital brain defects

KEY TERMS

Campbell’s Urology, edited by Patrick C. Walsh, et al.
Philadelphia: W. B. Saunders Co., 1998.

J. Ricker Polsdorfer, MD

Congenital—Present at birth.
Cystoscopy—Examination of the urinary bladder
with a thin telescope-like instrument.
Exstrophy—Being turned inside out combined with
being outside the body.
Diverticulum—A pouch extending from a hollow
organ.
Radiologist—A physician who specializes in creating images of the internal organs of the body.
Teratogen—Any agent that can cause birth defects.
Ureter—The tube that transports urine from the
kidney to the bladder.
Ureterovesical junction—The joining of the ureter
to the bladder.
Urologist—A surgeon who specializes in diseases
of the urinary system.

Alternative treatment
After surgery, ongoing precautions to reduce frequency of infection may need to be used. Cranberry
juice has the ability to keep bacteria from adhering to
the membranes and can help prevent infection whenever
there is increased risk. There are botanical and homeopathic treatments available; however, consultation by a
trained practitioner is recommended before treatment.

Prognosis
With immediate surgery, three-quarters of
patients can be successfully repaired. They will have
control of their urine and no long-term consequences.
The rate of infection is greater for those with congenital bladder anomalies, since any abnormality in the
urinary system predisposes it to invasion by bacteria.

Prevention
Birth defects often have no precisely identified
cause, therefore, prevention is limited to general measures such as early and continuous prenatal care,
appropriate nutrition, and a healthy lifestyle.
Resources
BOOKS

Gearhart, John P., and Robert D. Jeffs. ‘‘Exstrophyepispadias Complex and Bladder Anomalies.’’ In
976

Congenital bladder diverticulum see
Congenital bladder anomalies

I Congenital brain defects
Definition
Congenital brain defects are a group of disorders
of brain development.

Description
Brain development begins shortly after conception and continues throughout the growth of a fetus.
A complex genetic program coordinates the formation, growth, and migration of billions of neurons, or
nerve cells, and their development into discrete, interacting brain regions. Interruption of this program,
especially early in development, can cause structural
defects in the brain. In addition, normal brain formation requires proper development of the surrounding
skull, and skull defects may lead to brain malformation. Congenital brain defects may be caused by
inherited genetic defects, spontaneous mutations
within the genes of the embryo, or effects on the
embryo due to the mother’s infection, trauma, or
drug use.
Early on in development, a flat strip of tissue
along the back of the fetus rolls up to form a tube.
This so-called ‘‘neural tube’’ develops into the spinal
cord, and at one end, the brain. Closure of the tube is
required for subsequent development of the tissue
within. Anencephaly (literally ‘‘without brain’’),
results when the topmost portion of the tube fails to
close. Anencephaly is the most common severe malformation seen in stillborn births. It is about four
times more common in females than males.
Anencephaly is sometimes seen to run in families,
and for parents who have conceived one anencephalic
fetus, the risk of a second is as high as 5%. Fewer than
half of babies with anencephaly are born alive, and
survival beyond the first month is rare.
Encephalocele is a protrusion of part of the brain
through a defect in the skull. The most common site
for encephalocele is along the front-to-back midline of
the skull, usually at the rear, although frontal
GALE ENCYCLOPEDIA OF MEDICINE

Failure of neural-tube closure below the level of
the brain prevents full development of the surrounding
vertebral bones and leads to spina bifida, or a divided
spinal column. Incomplete closure causes protrusion
of the spinal cord and meninges, called meningomyelocele. Some cases of spina bifida are accompanied by
another defect at the base of the brain, known as the
Arnold-Chiari malformation or Chiari II malformation. For reasons that are unclear, part of the cerebellum is displaced downward into the spinal column.
Symptoms may be present at birth or delayed until
early childhood.
The Dandy-Walker malformation is marked by
incomplete formation, or absence of, the central section of the cerebellum, and the growth of cysts within
the lowest of the brain’s ventricles. The ventricles are
fluid-filled cavities within the brain, through which
cerebrospinal fluid (CSF) normally circulates. The
cysts may block the exit of the fluid, causing hydrocephalus. Symptoms may be present at birth or
delayed until early childhood.
Soon after closure of the neural tube, the brain
divides into two halves, or hemispheres. Failure of
division is termed holoprosencephaly (literally
‘‘whole forebrain’’). Holoprosencephaly is almost
always accompanied by facial and cranial deformities
along the midline, including cleft lip, cleft palate, fused
eye sockets and a single eye (cyclopia), and deformities
of the limbs, heart, gastrointestinal tract, and other
internal organs. Most infants are either stillborn or die
soon after birth. Survivors suffer from severe neurological impairments.
The normal ridges and valleys of the mature brain
are formed after cells from the inside of the developing
brain migrate to the outside and multiply. When these
cells fail to migrate, the surface remains smooth, a
condition called lissencephaly (‘‘smooth brain’’).
Lissencephaly is often associated with facial abnormalities including a small jaw, a high forehead, a short
nose, and low-set ears.
If damaged during growth, especially within the
first 20 weeks, brain tissue may stop growing, while
GALE ENCYCLOPEDIA OF MEDICINE

tissue around it continues to form. This causes an
abnormal cleft or groove to appear on the surface of
the brain, called schizencephaly (literally ‘‘split
brain’’). This cleft should not be confused with the
normal wrinkled brain surface, nor should the name
be mistaken for schizophrenia, a mental disorder.
Generalized destruction of tissue or lack of brain
development may lead to hydranencephaly, in
which cerebrospinal fluid fills much of the space
normally occupied by the brain. Hydranencephaly
is distinct from hydrocephalus, in which CSF
accumulates within a normally-formed brain, putting pressure on it and possibly causing skull
expansion.
Excessive brain size is termed megalencephaly
(literally ‘‘big brain’’). Megalencephaly is defined as
any brain size above the 98th percentile within the
population. Some cases are familial, and may be
entirely benign. Others are due to metabolic or neurologic disease. The opposite condition, microcephaly, may be caused by failure of the brain to
develop, or by intrauterine infection, drug toxicity,
or brain trauma.

Causes and symptoms
Causes
Congenital brain defects may have genetic, infectious, toxic, or traumatic causes. In most cases, no
certain cause can be identified.
GENETIC CAUSES. Some brain defects are caused
by trisomy, the inclusion of a third copy of a chromosome normally occurring in pairs. Most trisomies
occur because of improper division of the chromosomes during formation of eggs or sperm. Trisomy of
chromosome 9 can cause some cases of Dandy-Walker
and Chiari II malformation. Some cases of holoprosencephaly are caused by trisomy of chromosome 13,
while others are due to abnormalities in chromosomes
7 or 18. Individual gene defects, either inherited or
spontaneous, are responsible for other cases of congenital brain malformations.
DRUGS. Drugs known to cause congenital brain
defects when used by the mother during critical developmental periods include:


anticonvulsant drugs



retinoic acid and tretinoin



warfarin



alcohol



cocaine
977

Congenital brain defects

encephaloceles are more common among Asians.
Pressure within the skull pushes out cranial tissue.
The protective layer over the brain, the meninges,
grows to cover the protrusion, as does skin in some
cases. Defects in skull closure are thought to cause
some cases of encephalocele, while defects in neural
tube closure may cause others. Encephaloceles may be
small and contain little or no brain tissue, or may be
quite large and contain a significant fraction of the
brain.

Congenital brain defects

OTHER. Other causes of congenital brain defects

include:


intrauterine infections, including cytomegalovirus,
rubella, herpes simplex, and varicella zoster



maternal diabetes mellitus



maternal phenylketonuria



fetal trauma
Symptoms

Besides the features listed above, symptoms of
congenital brain defects may include:


Chiari II malformation: impaired swallowing and
gag reflex, loss of the breathing reflex, facial paralysis, uncontrolled eye movements (nystagmus),
impaired balance and gait.



Dandy-Walker malformation: symptoms of hydrocephalus, lack of muscle tone or ‘‘floppiness,’’ seizures, spasticity, deafness, irritability, visual
impairment,
deterioration
of
consciousness,
paralysis.



Lissencephaly: lack of muscle tone, seizures, developmental delay, spasticity, cerebral palsy.



Hydranencephaly: irritability, spasticity, seizures,
temperature oscillations.



Megalencephaly due to neurological or metabolic
disease: mental retardation, seizures.

KEY TERMS
Amniocentesis—Removal of fluid from the sac surrounding a fetus for purposes of diagnosis.
Cerebrospinal fluid—Fluid produced within the
brain for nutrient transport and structural purposes.
CSF circulates through the ventricles, open spaces
within the brain, and drains through the membranes surrounding the brain.
Congenital—Defect present at birth.
Fetus—The unborn human, developing in a
woman’s uterus, from the eighth week after fertilization to birth.

Chiari II, and some cases of hydranencephaly) may
be treated by installation of a drainage shunt for cerebrospinal fluid. Drugs may be used to treat some
symptoms of brain defects, including seizures and
spasticity.

Prognosis
Most congenital brain defects carry a very poor
prognosis. Surgical treatment of meningomyelocele
and encephalocele may be successful, with lasting neurological deficiencies, that vary in severity. Early treatment of hydrocephalus may prevent more severe brain
damage.

Diagnosis
Congenital brain defects are diagnosed either from
direct physical examination or imaging studies including
computed tomography scans (CT) and magnetic resonance imaging (MRI). Electroencephalography (EEG)
may be used to reveal characteristic abnormalities.
Prenatal diagnosis of neural tube defects causing
anencephaly or meningomyelocele is possible through
ultrasound examination and maternal blood testing
for alpha-fetoprotein, which is almost always elevated.
Ultrasound can also be used to diagnose DandyWalker and Chiari II malformations. Amniocentesis
may reveal trisomies or other chromosomal
abnormalities.

Prevention
Some cases of congenital brain defects can be
prevented with good maternal nutrition, including
folic acid supplements. Folic acid is a vitamin that
has been shown to reduce the incidence of neural
tube defects. Pregnant women should avoid exposure
to infection, especially during the first trimester.
Abstention from drugs and alcohol during pregnancy
may reduce risk. Genetic counseling is advisable for
parents who have had one child with anencephaly,
since the likelihood of having another is increased.
Resources
BOOKS

Treatment
Meningomyelocele may be treated with surgery to
close the open portion of the spinal cord. Surgery for
encephalocele is possible only if there is a minimal
amount of brain tissue protruding. Malformations
associated with hydrocephalus (Dandy-Walker,
978

Fenichel, G. M. Clinical Pediatric Neurology. 3rd ed.
W. B. Saunders Co., 1997.

Richard Robinson

Congenital defects see Birth defects
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Congenital heart disease, also called congenital
heart defect, includes a variety of malformations of the
heart or its major blood vessels that are present at birth.

Description
Congenital heart disease occurs when the heart or
blood vessels near the heart do not develop properly
before birth. Some infants are born with mild types of
congenital heart disease, but most need surgery in
order to survive. Patients who have had surgery are
likely to experience other cardiac problems later in life.
Most types of congenital heart disease obstruct the
flow of blood in the heart or the nearby vessels, or cause
an abnormal flow of blood through the heart. Rarer
types of congenital heart disease occur when the newborn has only one ventricle, or when the pulmonary
artery and the aorta come out of the same ventricle, or
when one side of the heart is not completely formed.
Patent ductus arteriosus
Patent ductus arteriosus refers to the opening of a
passageway—or temporary blood vessel (ductus)—to
carry the blood from the heart to the aorta before
birth, allowing blood to bypass the lungs, which are
not yet functional. The ductus should close spontaneously in the first few hours or days after birth. When
it does not close in the newborn, some of the blood
that should flow through the aorta then returns to the
lungs. Patent ductus arteriosus is common in premature babies, but rare in full-term babies. It also has
been associated with mothers who had German
measles (rubella) while pregnant.
Hypoplastic left heart syndrome
Hypoplastic left heart syndrome, a condition in
which the left side of the heart is underdeveloped, is
rare, but it is the most serious type of congenital heart
disease. With this syndrome, blood reaches the aorta,
which pumps blood to the entire body, only from the
ductus, which then normally closes within a few days
of birth. In hypoplastic left heart syndrome, the baby
seems normal at birth, but as the ductus closes, blood
cannot reach the aorta and circulation fails.
Obstruction defects
When heart valves, arteries, or veins are narrowed, they partly or completely block the flow of
GALE ENCYCLOPEDIA OF MEDICINE

Stenosis is a narrowing of the valves or arteries. In
pulmonary stenosis, the pulmonary valve does not
open properly, forcing the right ventricle to work
harder. In aortic stenosis, the improperly formed aortic valve is narrowed. As the left ventricle works
harder to pump blood through the body, it becomes
enlarged. In coarctation of the aorta, the aorta is constricted, reducing the flow of blood to the lower part of
the body and increasing blood pressure in the upper
body.
A bicuspid aortic valve has only two flaps instead
of three, which can lead to stenosis in adulthood.
Subaortic stenosis is a narrowing of the left ventricle
below the aortic valve that limits the flow of blood
from the left ventricle.
Septal defects
When a baby is born with a hole in the septum (the
wall separating the right and left sides of the heart),
blood leaks from the left side of the heart to the right,
or from a higher pressure zone to a lower pressure
zone. A major leakage can lead to enlargement of the
heart and failing circulation. The most common types
of septal defects are atrial septal defect, an opening
between the two upper heart chambers, and ventricular
septal defect, an opening between the two lower heart
chambers. Ventricular septal defect accounts for
about 15% of all cases of congenital heart disease in
the United States.
Cyanotic defects
Heart disorders that cause a decreased, inadequate amount of oxygen in blood pumped to the
body are called cyanotic defects. Cyanotic defects,
including truncus arteriosus, total anomalous pulmonary venous return, tetralogy of Fallot, transposition of the great arteries, and tricuspid atresia, result in
a blue discoloration of the skin due to low oxygen
levels. About 10% of cases of congenital heart disease
in the United States are tetralogy of Fallot, which
includes four defects. The major defects are a large
hole between the ventricles, which allows oxygen-poor
blood to mix with oxygen-rich blood, and narrowing
at or beneath the pulmonary valve. The other defects
are an overly muscular right ventricle and an aorta
that lies over the ventricular hole.
In transposition (reversal of position) of the great
arteries, the pulmonary artery and the aorta are
979

Congenital heart disease

I Congenital heart disease

blood. The most common obstruction defects are pulmonary valve stenosis, aortic valve stenosis, and coarctation of the aorta. Bicuspid aortic valve and subaortic
stenosis are less common.

Congenital heart disease

reversed, causing oxygen-rich blood to re-circulate to
the lungs while oxygen-poor blood goes to the rest of
the body. In tricuspid atresia, the baby lacks a triscupid valve and blood cannot flow properly from the
right atrium to the right ventricle.
Other defects
Ebstein’s anomaly is a rare congenital syndrome
that causes malformed tricuspid valve leaflets, which
allow blood to leak between the right ventricle and the
right atrium. It also may cause a hole in the wall
between the left and right atrium. Treatment often
involves repairing the tricuspid valve. Ebstein’s anomaly may be associated with maternal use of the psychiatric drug lithium during pregnancy.
Brugada syndrome is another rare congenital
heart defect that appears in adulthood and may
cause sudden death if untreated. Symptoms, which
include rapid, uneven heart beat, often appear at
night. Scientists believe that Brugada syndrome is
caused by mutations in the gene SCN5A, which
involves cardiac sodium channels.
Infants born with DiGeorge sequence can have
heart defects such as a malformed aortic arch and
tetralogy of Fallot. Researchers believe DiGeorge
sequence most often is caused by mutations in genes
in the region 22q11.
Marfan syndrome is a connective tissue disorder
that causes tears in the aorta. Since the disease also
causes excessive bone growth, most Marfan syndrome
patients are over six feet tall. In athletes, and others, it
can lead to sudden death. Researchers believe the
defect responsible for Marfan’s syndrome is found in
gene FBN1, on chromosome 15.
About 32,000 infants are born every year with
congenital heart disease, which is the most common
birth defect. About half of these cases require medical
treatment. More than one million people with heart
defects are currently living in the United States.

Causes and symptoms
In most cases, the causes of congenital heart disease are unknown. Genetic and environmental factors
and lifestyle habits can all be involved. The likelihood
of having a child with a congenital heart disease
increases if the mother or father, another child, or
another relative had congenital heart disease or a
family history of sudden death. In 2004, researchers
identified a chromosome deletion that might explain
some of the genetic causes of certain congenital heart
diseases.
980

Viral infections, such as German measles, can
produce congenital heart disease. Women with diabetes and phenylketonuria (an inherited liver condition
also called PKU) also are at higher risk of having
children with congenital heart defects. Many cases of
congenital heart disease result from the mother’s
excessive use of alcohol or taking illegal drugs, such
as cocaine, while pregnant. The mother’s exposure to
certain anticonvulsant and dermatologic drugs during
pregnancy also can cause congenital heart disease.
There are many genetic conditions, such as Down
syndrome, which affect multiple organs and can
cause congenital heart disease.
Symptoms of congenital heart disease in general
include: shortness of breath, difficulty feeding in
infancy, sweating, cyanosis (bluish discoloration of
the skin), heart murmur, respiratory infections that
recur excessively, stunted growth, and limbs and muscles that are underdeveloped.
Symptoms of specific types of congenital heart
disease are as follows:


Patent ductus arteriosus: quick tiring, slow growth,
susceptibility to pneumonia, rapid breathing. If the
ductus is small, there are no symptoms.



Hypoplastic left heart syndrome: ashen color, rapid
and difficult breathing, inability to eat.



Obstruction defects: cyanosis (skin that is discolored
blue), chest pain, tiring easily, dizziness or fainting,
congestive heart failure, and high blood pressure.



Septal defects: difficulty breathing, stunted growth.
Sometimes there are no symptoms.



Cyanotic defects: cyanosis, sudden rapid breathing
or unconsciousness, and shortness of breath and
fainting during exercise.

Diagnosis
Echocardiography and cardiac magnetic resonance
imaging (MRI) are used to confirm congenital heart
disease when it is suggested by the symptoms and
physical examination. An echocardiograph will display
an image of the heart that is formed by sound waves. It
detects valve and other heart problems. Fetal echocardiography is used to diagnose congenital heart disease
in utero, usually after 20 weeks of pregnancy. Between
10 and 14 weeks of pregnancy, physicians also may use
an ultrasound to look for a thickness at the nuchal
translucency, a pocket of fluid in back of the embryo’s
neck, which may indicate a cardiac defect in 55% of
cases. Cardiac MRI, a scanning method that uses
magnetic fields and radio waves, can help physicians
GALE ENCYCLOPEDIA OF MEDICINE

In children and adults, computed tomography
(CT) and MRI are the preferred methods to visualize
congenital heart disease. Contrast may be added to
enhance the image for the radiologist.

Treatment
Congenital heart disease is treated with drugs and/
or surgery. Drugs used include diuretics, which aid the
baby in excreting water and salts, and digoxin, which
strengthens the contraction of the heart, slows the
heartbeat, and removes fluid from tissues.
Surgical procedures seek to repair the defect as
much as possible and restore circulation to as close to
normal as possible. Sometimes, multiple surgical procedures are necessary. Surgical procedures include:
arterial switch, balloon atrial septostomy, balloon valvuloplasty, Damus-Kaye-Stansel procedure, Fontan
procedure, pulmonary artery banding, Ross procedure, shunt procedure, and venous switch or intraatrial baffle.
Arterial switch, to correct transposition of the
great arteries, involves connecting the aorta to the
left ventricle and connecting the pulmonary artery to
the right ventricle. Balloon atrial septostomy, also
done to correct transposition of the great arteries,
enlarges the atrial opening during heart catheterization. Balloon valvuloplasty uses a balloon-tipped
catheter to open a narrowed heart valve, improving
the flow of blood in pulmonary stenosis. It is sometimes used in aortic stenosis. Transposition of the
great arteries also can be corrected by the DamusKaye-Stansel procedure, in which the pulmonary
artery is cut in two and connected to the ascending
aorta and the farthest section of the right ventricle.
For tricuspid atresia and pulmonary atresia, the
Fontan procedure connects the right atrium to the
pulmonary artery directly or with a conduit, and
the atrial defect is closed. Pulmonary artery banding,
narrowing the pulmonary artery with a band to reduce
blood flow and pressure in the lungs, is used for ventricular septal defect, atrioventricular canal defect,
and tricuspid atresia. Later, the band can be removed
and the defect corrected with open-heart surgery.
To correct aortic stenosis, the Ross procedure
grafts the pulmonary artery to the aorta. For tetralogy
of Fallot, tricuspid atresia, or pulmonary atresia, the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Aorta—The main artery located above the heart
that pumps oxygenated blood out into the body.
Many congenital heart defects affect the aorta.
Congenital—Refers to a disorder that is present at
birth.
Cyanotic—Marked by bluish discoloration of the
skin due to a lack of oxygen in the blood. It is one of
the types of congenital heart disease.
Ductus—The blood vessel that joins the pulmonary
artery and the aorta. When the ductus does not
close at birth, it causes a type of congenital heart
disease called patent ductus arteriosus.
Electrocardiograph (ECG, EKG)—A test used to
measure electrical impulses coming from the
heart in order to gain information about its structure
or function.
Hypoplastic—Incomplete or underdevelopment
of a tissue or organ. Hypoplastic left heart syndrome is the most serious type of congenital heart
disease.
Neuchal translucency—A pocket of fluid at the
back of an embryo’s neck visible via ultrasound
that, when thickened, may indicate the infant will
be born with a congenital heart defect.
Septal—Relating to the septum, the thin muscle
wall dividing the right and left sides of the heart.
Holes in the septum are called septal defects.
Stenosis—The constricting or narrowing of an
opening or passageway.

shunt procedure creates a passage between blood vessels, sending blood into parts of the body that need it.
For transposition of the great arteries, venous switch
creates a tunnel inside the atria to re-direct oxygenrich blood to the right ventricle and aorta and venous
blood to the left ventricle and pulmonary artery.
When all other options fail, some patients may
need a heart transplant. Children with congenital
heart disease require lifelong monitoring, even after
successful surgery. The American Heart Association
recommends regular dental check-ups and the preventive use of antibiotics to protect patients from heart
infections, or endocarditis. However, a 2003 study
reported that preventive antibiotics are underused in
people with congenital heart disease. Many patients
did not understand the risk of endocarditis. Since
981

Congenital heart disease

evaluate congenital heart disease, but is not always
necessary. Physicians also may use a chest x ray to
look at the size and location of the heart and lungs, or
an electrocardiograph (ECG), which measures electrical impulses to create a graph of the heart beat.

Congenital hip dysplasia

children with congenital heart disease have slower
growth, nutrition is important. Physicians also may
limit their athletic activity.

Prognosis
The outlook for children with congenital heart
disease has improved markedly in the past two decades. Many types of congenital heart disease that
would have been fatal now can be treated successfully.
Because many children with these defects survive into
adulthood, physicians and patients are reminded that
the patients will require continued medical observation as they mature. Research on diagnosing heart
defects when the fetus is in the womb may lead to
future treatment to correct defects before birth.
Promising new prevention methods and treatments
include genetic screening and the cultivation of cardiac
tissue in the laboratory that could be used to repair
congenital heart defects. As scientists continue to
advance the study of genetics, they also will better
understand genetic causes of many congenital heart
diseases. For example, scientists just discovered a
potential cause of atrioventricular canal defects in
the fall of 2003.
Resources
BOOKS

Mayo Clinic Heart Book. New York: William Morrow and
Company, 2000.
Wild, C. L., and M. J. Neary. Heart Defects in Children:
What Every Parent Should Know. Minneapolis:
Chronimed Publishing, 2000.
Williams, R. A. The Athlete and Heart Disease. Philadelphia:
Lippincott Williams & Wilkins, 1999.
PERIODICALS

‘‘Adults With Congenital Heart Disease Need Continued
Medical Observation.’’ Cardiovascular Week August
23, 2004: 23.
‘‘AEP Underused for Congenital Heart Disease Patients.’’
Heart Disease Weekly August 31, 2003: 23.
‘‘Coping with Congenital Heart Disease in Your Baby.’’
American Family Physician 59 (April 1, 1999): 1867.
‘‘Deletions on Chromosome 1q21.1 Are Related to
Congenital Heart Disease.’’ Heart Disease Weekly
August 22, 2004: 50.
Hyett, Jon, et. al. ‘‘Using Fetal Nuchal Translucency to
Screen for Major Congenital Cardiac Defects at 10-14
Weeks: Population Based Cohort Study.’’ Lancet 318
(January 1999): 81-85.
‘‘MRI and CT Can Visualize Congenital Heart Disease.’’
Medical Devices & Surgical Technology Week August
22, 2004: 76.
‘‘New Insight Offered into the Genetics of Congenital Heart
Disease.’’ Heart Disease Weekly October 12, 2003: 3.
982

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave., Dallas,
TX 75231-4596. (214) 373-6300 or (800) 242-8721.
inquire@heart.org. <http://www.americanheart.org>.
Congenital Heart Disease Information and Resources. 1561
Clark Dr., Yardley, PA 19067. <http://
www.tchin.org>.
Texas Heart Institute Heart Information Service. PO Box
20345, Houston, TX 77225-0345. (800) 292-2221.
<http://www.tmc.edu/thi/his.html>.

Melissa Knopper
Teresa G. Odle

I Congenital hip dysplasia
Definition
A condition of abnormal development of the hip,
resulting in hip joint instability and potential dislocation of the thigh bone from the socket in the pelvis.
This condition has been more recently termed developmental hip dysplasia, as it often develops over the
first few weeks, months, or years of life.

Description
Congenital hip dysplasia is a disorder in children
that is either present at birth or shortly thereafter.
During gestation, the infant’s hip should be developing
with the head of the thigh bone (femur) sitting perfectly
centered in its shallow socket (acetabulum). The acetabulum should cover the head of the femur as if it were
a ball sitting inside of a cup. In the event of congenital
hip dysplasia, the development of the acetabulum in an
infant allows the femoral head to ride upward out of the
joint socket, especially when weight bearing begins.

Causes and symptoms
Clinical studies show a familial tendency toward hip
dysplasia, with more females affected than males. This
disorder is found in many cultures around the world.
However, statistics show that the Native American
population has a high incidence of hip dislocation. This
has been documented to be due to the common practice
of swaddling and using cradleboards for restraining the
infants. This places the infant’s hips into extreme adduction (brought together). The incidence of congenital hip
dysplasia is also higher in infants born by caesarian and
breech position births. Evidence also shows a greater
chance of this hip abnormality in the first born compared
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Acetabulum—The large cup-shaped cavity at the
junction of pelvis and femur or thigh bone.
Orthosis—A force system designed to control or
correct or compensate for a bone deformity,
deforming forces, or forces absent from the body.

Diagnosis
Because the abnormalities of this hip problem
often vary, a thorough physical examination is necessary for an accurate diagnosis of congenital hip dysplasia. The hip disorder can be diagnosed by moving
the hip to determine if the head of the femur is moving
in and out of the hip joint. One specific method, called
the Ortolani test, begins with each of the examiner’s
hands around the infant’s knees, with the second and
third fingers pointing down the child’s thigh. With the
legs abducted (moved apart), the examiner may be
able to discern a distinct clicking sound with motion.
If symptoms are present with a noted increase in
abduction, the test is considered positive for hip joint
instability. It is important to note this test is only valid
a few weeks after birth.
The Barlow method is another test performed with
the infant’s hip brought together with knees in full bent
position. The examiner’s middle finger is placed over
the outside of the hipbone while the thumb is placed on
the inner side of the knee. The hip is abducted to where
it can be felt if the hip is sliding out and then back in the
joint. In older babies, if there is a lack of range of
motion in one hip or even both hips, it is possible that
the movement is blocked because the hip has dislocated
and the muscles have contracted in that position. Also
in older infants, hip dislocation is evident if one leg
looks shorter than the other.
X-ray films can be helpful in detecting abnormal
findings of the hip joint. X rays may also be helpful in
finding the proper positioning of the hip joint for
treatments of casting. Ultrasound has been noted as
a safe and effective tool for the diagnosis of congenital
hip dysplasia. Ultrasound has advantages over x rays,
as several positions are noted during the ultrasound
procedure. This is in contrast to only one position
observed during the x ray.

Treatment
The objective of treatment is to replace the head of
the femur into the acetabulum and, by applying constant
pressure, to enlarge and deepen the socket. In the past,
stabilization was achieved by placing rolled cotton
GALE ENCYCLOPEDIA OF MEDICINE

diapers or a pillow between the thighs, thereby keeping
the knees in a frog like position. More recently, the
Pavlik harness and von Rosen splint are commonly
used in infants up to the age of six months. A stiff shell
cast may be used, which achieves the same purpose,
spreading the legs apart and forcing the head of the
femur into the acetabulum. In some cases, in older children between six to 18 months, surgery may be necessary
to reposition the joint. Also at this age, the use of closed
manipulation may be applied successfully, by moving
the leg around manually to replace joint. Operations are
not only performed to reduce the dislocation of the hip,
but also to repair a defect in the acetabulum. A cast is
applied after the operation to hold the head of the femur
in the correct position. The use of a home traction
program is now more common. However, after the age
of eight years, surgical procedures are primarily done for
pain reduction measures only. Total hip surgeries may be
inevitable later in adulthood.

Alternative treatment
Nonsurgical treatments include exercise programs, orthosis (a force system, often involving
braces), and medications. A physical therapist may
develop a program that includes strengthening,
range-of-motion exercises, pain control, and functional activities. Chiropractic medicine may be helpful,
especially the procedures of closed manipulations, to
reduce the dislocated hip joint.

Prognosis
Unless corrected soon after birth, abnormal stresses cause malformation of the developing femur, with
a characteristic limp or waddling gait. If cases of congenital hip dysplasia go untreated, the child will have
difficulty walking, which could result in life-long pain.
In addition, if this condition goes untreated, the
abnormal hip positioning will force the acetabulum
to locate to another position to accommodate the
displaced femur.
983

Congenital hip dysplasia

to the second or third child. Hormonal changes within
the mother during pregnancy, resulting in increased ligament laxity, is thought to possibly cross over to the
placenta and cause the baby to have lax ligaments
while still in the womb. Other symptoms of complete
dislocation include a shortening of the leg and limited
ability to abduct the leg.

Congenital lobar emphysema

Prevention

KEY TERMS

Prevention includes proper prenatal care to determine the position of the baby in the womb. This may
be helpful in preparing for possible breech births associated with hip problems. Avoiding excessive and prolonged infant hip adduction may help prevent strain
on the hip joints. Early diagnosis remains an important part of prevention of congenital hip dysplasia.

Congenital—A disease or condition that is present
at birth.
Emphysema—A condition in which the air sacs in
the lungs become overinflated, causing a decrease
in respiratory function.

Resources

Lobar—Relating to a lobe, a rounded projecting
part of the lungs.

ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914)
428-7100. resourcecenter@modimes.org. <http://
www.modimes.org>.

Jeffrey P. Larson, RPT

I Congenital lobar emphysema
Definition
Congenital lobar emphysema is a chronic disease
that causes respiratory distress in infants.

Description
Congenital lobar emphysema, also called infantile
lobar emphysema, is a respiratory disease that occurs
in infants when air enters the lungs but cannot leave
easily. The lungs become over-inflated, causing
respiratory function to decrease and air to leak out
into the space around the lungs.
Half of the cases of congenital lobar emphysema
occur in the first four weeks of life, and three-quarters
occur in infants less than six months old. Congenital
lobar emphysema is more common in boys than in
girls.
Each person has two lungs, right and left. The
right lung is divided into three sections, called lobes,
and the left lung into two lobes. Congenital lobar
emphysema usually affects only one lobe, and this is
usually an upper lobe. It occurs most frequently in the
left upper lobe, followed by the right middle lobe.

Congenital lobar emphysema is almost never of
genetic origin.
Symptoms of congenital lobar emphysema
include:


shortness of breath



wheezing



lips and fingernail beds that have a bluish tinge

Diagnosis
Congenital lobar emphysema is usually identified
within the first two weeks of the infant’s life. It is
diagnosed by respiratory symptoms and a chest
x ray, which shows the over-inflation of the affected
lobe and may show a blocked air passage.

Treatment
For infants with no, mild, or intermittent symptoms, no treatment is necessary. For more serious
cases of congenital lobar emphysema, surgery is
necessary, usually a lobectomy to remove the affected
lung lobe.

Alternative treatment
Alternative treatments that may be helpful for
congenital lobar emphysema are aimed at supporting
and strengthening the patient’s respiratory function.
Vitamin and mineral supplementation may be recommended as may herbal remedies such as lobelia
(Lobelia inflata) that strengthen the lungs and enhance
their elasticity. Homeopathic constitutional care may
also be beneficial for this condition.

Causes and symptoms
The cause of congenital lobar emphysema often
cannot be identified. The airway may be obstructed or
the infant’s lungs may not have developed properly.
984

Prognosis
Surgery for congenital lobar emphysema has
excellent results.
GALE ENCYCLOPEDIA OF MEDICINE

Congenital
prevented.

lobar

emphysema

cannot



Duplication of ureters is quite common, either in
part or completely. Kidneys are sometimes duplicated as well. Someone may have four kidneys and
four ureters or two kidneys, half of each drained by
a separate ureter, or a single kidney with two, three,
or four ureters attached. As long as urine can flow
easily in the correct direction, such malformations
may never be detected. If, however, one of the
ureters has a dead end, a stricture or stenosis (narrowing), or a leaky ureterovesical valve (valve
between the ureter and bladder), infection is the
likely result.



Stricture or stenosis of a ureter prevents urine from
flowing freely. Whenever flow is obstructed in the
body–urine, bile, mucus, or any other liquid–infection follows. Ureters can be obstructed anywhere
along their course, though the ureterovesical valve
is the most common place.



A ureter may have an ectopic (out of place) orifice
(opening)–it may enter the bladder, or even another
structure, where it does not belong and therefore
without an adequate valve to control reflux.



The primary ureter, or a duplicate, may not even
reach the bladder, but rather terminate in a dead
end. Urine will stagnate there and eventually cause
infection.



A ureter can be perfectly normal but in the wrong
place, such as behind the vena cava (the large vein in
the middle of the abdomen). A so-called retrocaval
ureter may be pinched by the vena cava so that flow
is hindered. Other aberrant locations may also lead
to compression and impaired flow.

be

Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Jewish Center for Immunology and Respiratory
Medicine. 1400 Jackson St., Denver, CO 80206. (800)
222-5864. <http://www.nationaljewish.org/
main.html>.

Lori De Milto

Congenital megacolon see Hirschsprung’s
disease
Congenital thymic hypoplasia see DiGeorge
syndrome

I Congenital ureter anomalies
Definition
The ureter drains urine from the kidney into the
bladder. It is not simply a tube but an active organ that
propels urine forward by muscular action. It has a
valve at its bottom end that prevents urine from flowing backward into the kidney. Normally there is one
ureter on each side of the body for each kidney.
However, among the many abnormalities of ureteral
development, duplication is quite common. Ureters
may also be malformed in a variety of ways–some
harmful, others not.

Description
The urogenital system, for some reason, is more
likely than any other to have birth defects, and they
can occur in endless variety. Ureters can be duplicated
completely or partially, they can be in the wrong place,
they can be deformed, and they can end in the wrong
place. The trouble these abnormalities bring is directly
related to their effect on the flow of urine. As long as
urine flows normally through them, and only in one
direction, no harm is done.
GALE ENCYCLOPEDIA OF MEDICINE

Besides infection, urine that backs up will cause
the ureter and the kidney to dilate. Eventually, the
kidney will stop functioning because of the back pressure. This condition is called hydronephrosis–a kidney
swollen with urine.

Causes and symptoms
The causes of birth defects are multiple and often
unknown. Furthermore, the precise cause of specific
birth defects has only rarely been identified. Such is the
case with congenital ureteral anomalies.
Practically the only symptom generated by ureteral abnormalities is urinary tract infection. A lower
tract infection–in the bladder–is called cystitis. In children, it may cause fever and systemic symptoms, but in
adults it causes only cloudy, burning, and frequent
urine. Upper tract infections, on the other hand, can
be serious for both adults and children, causing high
fevers, back pain, severe generalized discomfort, and
985

Congenital ureter anomalies

Prevention

Congestive cardiomyopathy

even leading to kidney failure or septicemia (infection
spreading throughout the body by way of the blood
stream).
In rare cases, urine from an ectopic ureter will
bypass the bladder and dribble out of the bottom
somewhere, through a natural orifice like the vagina
or a completely separate unnatural opening.

Diagnosis
Serious or recurrent urinary infections will
prompt a search for underlying abnormalities.
Cystoscopy (looking into the bladder with a thin telescope-like instrument) and x rays with a contrast agent
to illuminate the urinary system will usually identify
the defect. Computed tomography scans (CT) and
Magnetic resonance imaging (MRI) may provide additional information. Urine cultures to identify the
infecting germs will be repeated frequently until the
problem is corrected.

KEY TERMS
Congenital—Present at birth.
Contrast agent—A chemical or other substance
placed in the body to show structures that would not
otherwise be visible on x ray or other imaging studies.
Cystoscopy—Looking into the urinary bladder with
a thin telescope-like instrument.
Ectopic—Out of place.
Septicemia—A serious whole body infection
spreading through the blood stream.
Ureterovesical valve—A sphincter (an opening
controlled by a circular muscle), located where
the ureter enters the bladder, that keeps urine
from flowing backward toward the kidney.
Urogenital—Both the urinary system and the sexual organs, which form together in the developing
embryo.

Treatment
Sometimes the recurring infections caused by flow
abnormalities can be treated with repeated and changing courses of antibiotics. Over time, the infecting
germs develop resistance to most treatments, especially the safer ones. If it can be done with acceptable
risk, it is better to repair the defect surgically.
Urologists have an arsenal of approaches to urine
drainage that range from simply reimplanting a ureter
into the bladder, in such a way that an effective valve is
created, to building a new bladder out of a piece of
bowel.

Alternative treatment
There are botanical and homeopathic treatments
available for urinary tract infection. None can take the
place of correcting a problem that is occurring because
of a malformed or dysfunctional organ system. Once
correction of the cause is addressed and there is unimpeded flow of urine, adequate fluid intake can contribute to prevention of future infections.

Prognosis
As long as damage to the kidneys from infection
or back pressure has not become significant, the surgical repair of troublesome ureteral defects produces
excellent long-term results in the great majority of
cases. Monitoring for recurrent infections is always a
good idea, and occasional checking of kidney function
will detect hidden ongoing damage.
986

Resources
BOOKS

Bauer, Stuart B. ‘‘Anomalies of the Kidney and
Ureteropelvic Junction.’’ In Campbell’s Urology, edited
by Patrick C. Walsh, et al. Philadelphia: W. B. Saunders
Co., 1998.

J. Ricker Polsdorfer, MD

I Congestive cardiomyopathy
Definition
Cardiomyopathy is an ongoing disease process that
damages the muscle wall of the lower chambers of the
heart. Congestive cardiomyopathy is the most common
form of cardiomyopathy. In congestive cardiomyopathy, also called dilated cardiomyopathy, the walls of the
heart chambers stretch (dilate) to hold a greater volume
of blood than normal. Congestive cardiomyopathy is
the final stage of many heart diseases and the most
common condition resulting in congestive heart failure.

Description
About 50,000 Americans develop cardiomyopathy each year. Of those, 87% have congestive
GALE ENCYCLOPEDIA OF MEDICINE

When the heart muscle is damaged by a disease
process, it cannot pump enough blood to meet the
body’s needs. Uninjured areas of the walls of the two
lower heart chambers (called ventricles) stretch to
make up for the lost pumping action. At first, the
enlarged chambers allow more blood to be pumped
with less force. The stretched muscle can also contract
more forcefully. Over time, the heart muscle continues
to stretch, ultimately becoming weaker. The heart is
forced to work harder to pump blood by beating
faster. Eventually it cannot keep up, and blood backs
up into the veins, legs, and lungs. When this happens,
the condition is called congestive heart failure.
Congestive cardiomyopathy usually affects both
ventricles. Blood backed up into the lungs from the left
ventricle causes fluid to congest the lung tissue. This is
called pulmonary edema. When the right ventricle fails
to pump enough blood, blood backs up into the veins
causing edema in the legs, feet, ankles, and abdomen.

Causes and symptoms
Congestive cardiomyopathy may be caused by a
number of conditions. Cardiomyopathy with a known
cause is called secondary cardiomyopathy. When no
cause can be identified, it is called primary cardiomyopathy or idiopathic cardiomyopathy. About 80% of
all cases of cardiomyopathy do not have a known
cause. Many heart specialists think that many cases
of idiopathic congestive cardiomyopathy may be
caused by a viral infection. Because cardiomyopathy
may occur many years after a viral infection and
viruses sometimes go undetected in laboratory tests,
it is difficult to know if a virus is the cause. Some
people have a weak heart from advanced coronary
artery disease that causes heart muscle damage. This
is sometimes called ischemic cardiomyopathy.
Conditions that can cause congestive cardiomyopathy are:

coronary artery disease, the arteries supplying blood
to the heart become narrowed or blocked. When blood
flow to an area of the heart is completely blocked, the
person has a heart attack. The heart muscle suffers
damage when its blood supply is reduced or blocked.
Significant recurrent muscle damage can occur
silently. This damage can lead to congestive
cardiomyopathy.
Infections caused by bacteria, viruses, and other
microorganisms can involve the heart, causing inflammation of the heart muscle (myocarditis). The inflammation may damage the heart muscle and cause
congestive cardiomyopathy. In the United States, the
coxsackievirus B is the most common cause of viral
congestive cardiomyopathy.
Myocarditis can also be caused by noninfectious
disorders. For example, the conditions sarcoidosis,
granulomatous myocarditis, and Wegener’s granulomatosis cause inflammation and tissue death in the
heart muscle.
Years of drinking excessive amounts of alcohol
can weaken the heart muscle, leading to congestive
cardiomyopathy. Other drugs and toxins, such as
cocaine, pesticides, and other chemicals, may have
the same effect.
High blood pressure (hypertension) puts extra
pressure on blood vessels and the heart. This increased
pressure makes the heart work harder to pump blood,
which may thicken and damage the chamber walls.
Severe nutritional deficiencies can weaken the
heart muscle and affect its pumping ability. Certain
disorders of metabolism, including diabetes mellitus
and thyroid disorders, can also lead to congestive
cardiomyopathy.
Occasionally, inflammation of the heart muscle
and congestive cardiomyopathy may develop late in
pregnancy or shortly after a woman gives birth. This
type of congestive cardiomyopathy is called peripartum cardiomyopathy. The cause of congestive cardiomyopathy in pregnancy is not known.



coronary artery disease



infections



noninfectious inflammatory conditions



alcohol and other drugs or toxins



hypertension



nutritional and metabolic disorders



pregnancy

Congestive cardiomyopathy usually is a chronic
condition, developing gradually over time. Patients
with early congestive cardiomyopathy may not have
symptoms. The most common symptoms are fatigue
and shortness of breath on exertion. Unfortunately,
sudden cardiac death is not uncommon with this condition. It stems from irregular heart rhythms in the
ventricles (ventricular arrhythmias).

Coronary artery disease is one of the most common causes of congestive cardiomyopathy. In

Patients with more advanced congestive cardiomyopathy may also have chest or abdominal pains,

GALE ENCYCLOPEDIA OF MEDICINE

987

Congestive cardiomyopathy

cardiomyopathy. Primary cardiomyopathy accounts
for only 1% of all deaths from heart disease.

Congestive cardiomyopathy

extreme tiredness, dizziness, and swelling of the legs
and ankles.

Diagnosis
Diagnosis of congestive cardiomyopathy is based
on:


symptoms



medical history



physical examination



chest x ray



electrocardiogram (ECG; also called EKG)



echocardiogram



cardiac catheterization

The diagnosis is based on the patient’s symptoms,
a complete physical examination, and tests that detect
abnormalities of the heart chambers. The physician
listens to the heart with a stethoscope to detect abnormal heart rhythms and heart sounds. A heart murmur
might mean that the heart valves are not closing properly due to the ventricles being enlarged.
A chest x ray can show if the heart is enlarged and if
there is fluid in the lungs. Abnormalities of heart valves
and other structures may also be seen on a chest x ray.
An electrocardiogram provides a record of electrical
changes in the heart muscle during the heartbeat. It gives
information on the heart rhythm and can show if the
heart chamber is enlarged. An ECG can detect damage
to the heart muscle and the amount of damage.
Echocardiography uses sound waves to make
images of the heart. These images can show if the
heart wall or chambers are enlarged and if there are
any abnormalities of the heart valves. Echocardiography can also evaluate the pumping efficiency of the
ventricles.
Cardiac catheterization usually is only used if a
diagnosis cannot be made with other methods. In
cardiac catheterization, a small tube (called a catheter)
is inserted into an artery and passed into the heart. It is
used to measure pressure in the heart and the amount
of blood pumped by the heart. A small tissue sample of
the heart muscle can be removed through the catheter
for examination under a microscope (biopsy). This
biopsy can show the type and amount of damage to
the heart muscle.

Treatment
When a patient is diagnosed with congestive cardiomyopathy, physicians try to find out the cause. If
988

coronary artery disease is not the culprit, in most other
cases a cause is not identified. When a condition
responsible for the congestive cardiomyopathy is diagnosed, treatment is aimed at correcting the underlying
condition. Congestive cardiomyopathy caused by
drinking excess alcohol or by drugs or toxins can be
treated by eliminating the alcohol or toxin completely.
In some cases, the heart may recover after the toxic
substance is removed from the body. Bacterial myocarditis is treated with an antibiotic to eliminate the
bacteria.
There is no cure for idiopathic congestive cardiomyopathy. Medicines are given to reduce the workload of the heart and to relieve the symptoms.
One or more of the following types of medicines
may be prescribed for congestive cardiomyopathy:


digitalis



diuretics



vasodilators



beta blockers



angiotensin converting enzyme inhibitors (ACE
inhibitors)



angiotensin receptor blockers

Digitalis helps the heart muscle to have stronger
pumping action. Diuretics help eliminate excess salt
and water from the kidneys by making patients urinate
more often. This helps reduce the swelling caused by
fluid buildup in the tissues. Vasodilators, beta blockers, and ACE inhibitors lower blood pressure and
expand the blood vessels so blood can move more
easily through them. This action makes it easier for
the heart to pump blood through the vessels.
Patients may also be given anticoagulant medications to prevent clots from forming due to pooling of
blood in the heart chambers. Medicines to prevent
abnormal heart rhythms (arrhythmias) may be given,
but some of these drugs can also reduce the force of
heart contractions. Automatic implantable cardioverter defibrillators (AICDs) can treat life-threatening
arrhythmias, which are relatively common in severe
cardiomyopathy.
Certain lifestyle changes may help reduce the
workload on the heart and relieve symptoms. Some
patients may need to change their diet, stop drinking
alcohol, begin a physician-supervised exercise program, and/or stop smoking.
Severe congestive cardiomyopathy usually causes
heart failure. When the heart muscle is damaged so
severely that medicines cannot help, a heart transplant
may be the only remaining treatment to be considered.
GALE ENCYCLOPEDIA OF MEDICINE

The outlook for a patient with congestive cardiomyopathy depends on the severity of the disease and
the person’s health. Generally, congestive cardiomyopathy worsens over time and the prognosis is not
good. About 50% of patients with congestive cardiomyopathy live for five years after the diagnosis.
Twenty five percent of patients are alive 10 years
after diagnosis. Women with congestive cardiomyopathy live twice as long as men with the disease. Many
of the deaths are caused by sudden abnormal heart
rhythms.

Prevention
Because idiopathic congestive cardiomyopathy
does not have a known cause, there is no sure way to
prevent it. The best way to prevent congestive cardiomyopathy is to avoid known causes such as
drinking excess alcohol or taking toxic drugs.
Eating a nutritious diet and getting regular exercise
to improve overall fitness also can help the heart to
stay healthy.
Congestive cardiomyopathy may also be prevented by identifying and treating any conditions
that might damage the heart muscle. These include
high blood pressure and coronary artery disease.
Regular blood pressure checks and obtaining
immediate medical care for hypertension and symptoms of coronary artery disease, such as chest pain,
are important to keep the heart functioning
properly.
Finally, diagnosing and treating congestive cardiomyopathy before the heart becomes severely
damaged may improve the outlook.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. P.O. Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Toni Rizzo

Congestive heart failure see Heart failure
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Angiotensin-converting enzyme (ACE) inhibitor—
A drug that relaxes blood vessel walls and lowers
blood pressure.
Atherosclerosis—Buildup of a fatty substance called
a plaque inside blood vessels.
Cardiac catheterization—A diagnostic test for
evaluating heart disease; a catheter is inserted
into an artery and passed into the heart.
Cardiomyopathy—Disease of the heart muscle.
Congestive cardiomyopathy—Also called dilated
cardiomyopathy; cardiomyopathy in which the
walls of the heart chambers stretch, enlarging the
heart ventricles so they can hold a greater volume
of blood than normal.
Coxsackievirus B—A type of virus in the group
Enterovirus that causes an infection similar to
polio, but without paralysis.
Digitalis—A drug that helps the heart muscle to
have stronger pumping action.
Dilated cardiomyopathy—Also called congestive
cardiomyopathy; cardiomyopathy in which the
walls of the heart chambers stretch, enlarging the
heart ventricles so they can hold a greater volume
of blood than normal.
Diuretic—A type of drug that helps the kidneys
eliminate excess salt and water.
Edema—Swelling caused by fluid buildup in tissues.
Granulomatous myocarditis —Also called giant
cell myocarditis, this noninfectious inflammation
of the heart causes large areas of tissue death in the
heart muscle, ventricular enlargement, and clots
inside the heart chambers.
Idiopathic
cardiomyopathy—Cardiomyopathy
without a known cause.
Sarcoidosis—A chronic disease that causes formation of abnormal areas containing inflammatory
cells, called granulomas, in any organ or tissue; in
the heart, large areas of the heart muscle can be
involved, causing cardiomyopathy.
Vasodilator—Any drug that relaxes blood vessel
walls.
Ventricle—One of the two lower chambers of the
heart.
Wegener’s granulomatosis—A disease usually
affecting males that causes the infiltration of
inflammatory cells and tissue death in the lungs,
kidneys, blood vessels, heart, and other tissues.

989

Congestive cardiomyopathy

Prognosis

Conjunctivitis

I Conjunctivitis
Definition
Conjuctivitis is an inflammation or redness of the
lining of the white part of the eye and the underside of
the eyelid (conjunctiva) that can be caused by infection, allergic reaction, or physical agents like infrared
or ultraviolet light.

Description
Conjunctivitis is the inflammation of the conjunctiva, a thin, delicate membrane that covers the
eyeball and lines the eyelid. Conjunctivitis is an extremely common eye problem because the conjunctiva is
continually exposed to microorganisms and environmental agents that can cause infections or allergic
reactions. Conjunctivitis can be acute or chronic
depending upon how long the condition lasts, the
severity of symptoms, and the type of organism or
agent involved. It can also affect one or both eyes
and, if caused by infection, can be very easily transmitted to others during close physical contact, particularly among children in a daycare center. Other
names for conjunctivitis include pink eye and red eye.

Causes and symptoms
Conjunctivitis may be caused by a viral infection,
such as a cold, acute respiratory infection, or disease
such as measles, herpes simplex, or herpes zoster.
Symptoms include mild to severe discomfort in one
or both eyes, redness, swelling of the eyelids, and
watery, yellow, or green discharge. Symptoms may
last anywhere from several days to two weeks.
Infection with an adenovirus, however, may also
cause a significant amount of pus-like discharge and
a scratchy, foreign body-type of sensation in the eye.
This may also be accompanied by swelling and tenderness of the lymph nodes near the ear.
Bacterial conjunctivitis can occur in adults and
children and is caused by organisms such as
Staphylococcus, Streptococcus, and Hemophilus.
Symptoms of bacterial conjunctivitis include a puslike discharge and crusty eyelids after awakening.
Redness of the conjunctiva can be mild to severe and
may be accompanied by swelling. Persons with symptoms of conjunctivitis who are sexually active may
possibly be infected with the bacteria that cause either
gonorrhea or chlamydia. There may be large amounts
of pus-like discharge, and symptoms may include
intolerance to light (photophobia), watery mucous
990

This person has severe conjunctivitis, most likely caused by
an allergic reaction. (Custom Medical Stock Photo. Reproduced
by permission.)

discharge, and tenderness in the lymph nodes near
the ear that may persist for up to three months.
Conjunctivitis may also be caused by environmental hazards, such as wind, smoke, dust, and allergic
reactions caused by pollen, dust, or grass. Symptoms
range from itching and redness to a mucous discharge.
Persons who wear contact lenses may develop allergic
conjunctivitis caused by the various eye solutions and
foreign proteins contained in them.
Other less common causes of conjunctivitis
include exposure to sun lamps or the electrical arcs
used during welding, and problems with inadequate
drainage of the tear ducts.

Diagnosis
An accurate diagnosis of conjunctivitis centers on
taking a patient history to learn when symptoms
began, how long the condition has been going on, the
symptoms experienced, and other predisposing factors, such as upper respiratory complaints, allergies,
sexually transmitted diseases, herpes simplex infections, and exposure to persons with pink eye. It may
be helpful to learn whether an aspect of an individual’s
occupation may be the cause, for example, welding.
Diagnostic tests are usually not indicated unless initial
treatment fails or an infection with gonorrhea or chlamydia is suspected. In such cases, the discharge may be
cultured and Gram stained to determine the organism
responsible for causing the condition. Cultures and
smears are relatively painless.

Treatment
The treatment of conjunctivitis depends on what
caused the condition. In all cases, warm compresses
GALE ENCYCLOPEDIA OF MEDICINE

Conjunctiva

Cornea
Lens

Conjunctivitis is the inflammation of the conjunctiva, a thin,
delicate membrane that covers the eyeball and lines the eyelid. It may be caused by a viral infection, such as a cold or
acute respiratory infection, or by such diseases as measles,
herpes simplex, or herpes zoster. (Illustration by Electronic
Illustrators Group.)

applied to the affected eye several times a day may help
to reduce discomfort. Some treatment choices will be
based on patient preference, convenience of use, and
cost to the patient.
Conjunctivitis due to a viral infection, particularly
those due to adenoviruses, are usually treated by
applying warm compresses to the eye(s) and applying
topical antibiotic ointments to prevent secondary bacterial infections.
Viral conjunctivitis caused by herpes simplex
should be referred to an ophthalmologist. Topical
steroids are commonly prescribed in combination
with antiviral therapy.
In cases of bacterial conjunctivitis, a physician
may prescribe an antibiotic eye ointment or eye
drops containing sodium sulfacetamide (Sulamyd) to
be applied daily for seven to 14 days. If, after 72 hours,
the condition does not improve, a physician or primary care provider should be notified because the
bacteria involved may be resistant to the antibiotic
used or the cause may not be bacterial.
For cases of conjunctivitis caused by a gonococcal
organism, a physician may prescribe an intramuscular
injection of ceftriaxone (Rocephin) and a topical antibiotic ointment containing erythromycin or bactracin
to be applied four times daily for two to three weeks.
Sexual partners should also be treated.
GALE ENCYCLOPEDIA OF MEDICINE

With accompanying chlamydia infection, a topical antibiotic ointment containing erythromycin
(Ilotycin) may be prescribed to be applied one to two
times daily. In addition, oral erythromycin or tetracycline therapy may be indicated for three to four weeks.
Again, sexual partners should also be treated.
Allergic conjunctivitis can be treated by removing
the allergic substance from a person’s environment, if
possible; by applying cool compresses to the eye; and
by administering eye drops four to six times daily for
four days. Also, oral antihistamines may help to relieve
itchy eyes. However, many of these drugs also dry the
eyes. Therefore, many physicians suggest a combination of antihistamines and lubricating drops or the use
of nasal corticosteroid sprays to help relieve allergic
conjunctivitis, particularly when it is combined with
nasal symptoms.

Alternative treatment
Conjunctivitis caused by gonococcal and chlamydial infection usually requires conventional medical
treatment. With bacterial, viral, and allergic conjunctivitis, however, alternative options can be helpful.
Internal immune enhancement with supplementation
can aid in the resolution of bacterial and viral conjunctivitis. Removal of the allergic agent is an essential
step in treating allergic conjunctivitis. As with any of
the recommended treatments, however, if no improvement is seen within 48–72 hours, a physician should be
consulted.
Homeopathically, there are a number of acute
remedies designed to treat conjunctivitis. These
include Pulsatilla (windflower, Pulsatilla nigricans),
Belladonna, and eyebright (Euphrasia officinalis).
Eye drops, prepared with homeopathic remedies
and/or herbs, can be a good substitute for pharmaceutical eye drops. Eye washes can also be made.
Herbal eyewashes made with eyebright (1 tsp. dried
herb steeped in 1 pint of boiling water) or chamomile (Matricaria recutita; 2–3 tsp. in 1 pint of boiling
water) may be helpful. Eyewashes should be strained
and cooled before use, and close attention should be
paid to make sure that any solution put into the eye
is sterile.
Other simple home remedies may help relieve the
discomfort associated with conjunctivitis. A boric acid
eyewash can be used to clean and soothe the eyes. A
warm compress applied to the eyes for five to
10 minutes three times a day can help relieve the discomfort of bacterial and viral conjunctivitis. A cool
compress or cool, damp tea bags placed on the eyes
can ease the discomfort of allergic conjunctivitis.
991

Conjunctivitis

Eyelid

Constipation



Frequently washing hands using antiseptic soap, and
using single-use towels during the disease to prevent
spreading the infection.



Avoiding chemical irritants and known allergens.



If in an area where welding occurs, using the proper
protective eye wear and screens to prevent damaging
the eyes.



Using a clean tissue to remove discharge from eyes,
and wash hands to prevent the spread of infection.



If medication is prescribed, finishing the course of
antibiotics, as directed, to make sure that the infection is cleared up and does not recur.



Avoiding contact, such as vigorous physical activities, with other persons until symptoms resolve.

KEY TERMS
Adenovirus—A virus that affects the upper respiratory tract.
Chlamydia—The most common bacterial sexually
transmitted disease in the United States that often
accompanies gonorrhea and is known for its lack of
evident symptoms in the majority of women.
Gonococcal—The bacteria Neisseria gonorrheae
that causes gonorrhea, a sexually transmitted infection of the genitals and urinary tract. The gonococcal organism may occasionally affect the eye,
causing blindness if not treated.
Herpes simplex virus—A virus that can cause fever
and blistering on the skin, mucous membranes, or
genitalia.

Resources

Herpes zoster virus—Acute inflammatory virus
that attacks the nerve cells on the root of each
spinal nerve with skin eruptions along a sensory
nerve ending.
Staphylococcus—A bacterial organism, looking
much like a cluster of grapes, that can infect various
body systems.

PERIODICALS

Streptococcus—An organism that causes infections of either the upper respiratory or gastrointestinal tract.

Griffith, H. Winter. ‘‘Conjunctivitis (Pink Eye).’’
ThriveOnline. <http://thriveonline.oxygen.com>.

Prewitt, Dawn. ‘‘Keep an Eye Toward the Nose: These
Treatments Can Help Stop the Charge of
Rhinoconjunctivitis.’’ Review of Optometry June 15,
2004: 125–127.
‘‘Topical Drugs for Treating Conjunctivitis.’’ GP June 14,
2004: 12.
OTHER

Lisa Papp, RN
Teresa G. Odle

Prognosis
If treated properly, the prognosis for conjunctivitis is good. Conjunctivitis caused by an allergic
reaction should clear up once the allergen is removed.
However, allergic conjunctivitis will likely recur if the
individual again comes into contact with the particular allergen. Conjunctivitis caused by bacteria or a
virus, if treated properly, is usually resolved in 10–14
days. If there is no relief of symptoms in 48–72 hours,
or there is moderate to severe eye pain, changes in
vision, or the conjunctivitis is suspected to be caused
by herpes simplex, a physician should be notified
immediately. If untreated or if treatment fails and is
not corrected, conjunctivitis may cause visual impairment by spreading to other parts of the eye, such as
the cornea.

Prevention
Conjunctivitis can, in many cases, be prevented,
or at least the course of the disease can be shortened by
following some simple practices.
992

Consciousness disorders see Coma

I Constipation
Definition
Constipation is an acute or chronic condition in
which bowel movements occur less often than usual or
consist of hard, dry stools that are painful or difficult
to pass. Bowel habits vary, but an adult who has not
had a bowel movement in three days or a child who
has not had a bowel movement in four days is considered constipated.

Description
Constipation is one of the most common medical
complaints in the United States. Constipation can
occur at any age, and is more common among individuals who resist the urge to move their bowels at their
GALE ENCYCLOPEDIA OF MEDICINE

Constipation is more common in women than in
men and is especially apt to occur during pregnancy.
Age alone does not increase the frequency of constipation, but elderly people (especially women) are more
likely to suffer from constipation.

Constipation can also be a side effect of:

Constipation

body’s signal. This often happens when children start
school or enter daycare and feel shy about asking
permission to use the bathroom.



aluminum salts in antacids



antihistamines



antipsychotic drugs



aspirin



belladonna (Atopa belladonna, source of atropine, a
medication used to relieve spasms and dilate the
pupils of the eye)



beta blockers (medications used to stabilize irregular
heartbeat, lower high blood pressure, reduce chest
pain)



blood pressure medications



calcium channel blockers (medication prescribed to
treat high blood pressure, chest pain, some types of
irregular heartbeat and stroke, and some non-cardiac
diseases)

Although this condition is rarely serious, it can
lead to:


bowel obstruction



chronic constipation



hemorrhoids (a mass of dilated veins in swollen tissue
around the anus)



hernia (a protrusion of an organ through a tear in the
muscle wall)



spastic colitis (irritable bowel syndrome, a condition
characterized by alternating periods of diarrhea and
constipation)



diuretics (drugs that promote the formation and
secretion of urine)

laxative dependency



iron or calcium supplements



narcotics (potentially addictive drugs that relieve
pain and cause mood changes)



tricyclic antidepressants (medications prescribed to
treat chronic pain, depression, headaches, and other
illnesses)



Chronic constipation may be a symptom of colorectal cancer, depression, diabetes, diverticulosis (small
pouches in the muscles of the large intestine), lead
poisoning, or Parkinson’s disease.
In someone who is elderly or disabled, constipation may be a symptom of bowel impaction, a more
serious condition in which feces are trapped in the
lower part of the large intestine. A doctor should be
called if an elderly or disabled person is constipated for
a week or more or if a child seems to be constipated.
A doctor should be notified whenever constipation occurs after starting a new prescription, vitamin,
or mineral supplement or is accompanied by blood in
the stools, changes in bowel patterns, or fever and
abdominal pain.

Causes and symptoms
Constipation usually results from not getting
enough exercise, not drinking enough water, or from
a diet that does not include an adequate amount of
fiber-rich foods like beans, bran cereals, fruits, raw
vegetables, rice, and whole-grain breads.
Other causes of constipation include anal fissure
(a tear or crack in the lining of the anus); chronic
kidney failure; colon or rectal cancer; depression;
hypercalcemia (abnormally high levels of calcium in
the blood); hypothyroidism (underactive thyroid
gland); illness requiring complete bed rest; irritable
bowel syndrome; and stress.
GALE ENCYCLOPEDIA OF MEDICINE

An adult who is constipated may feel bloated,
have a headache, swollen abdomen, or pass rock-like
feces; or strain, bleed, or feel pain during bowel movements. A constipated baby may strain, cry, draw the
legs toward the abdomen, or arch the back when having a bowel movement.

Diagnosis
Everyone becomes constipated once in a while,
but a doctor should be notified if significant changes
in bowel patterns last for more than a week or if
symptoms continue more than three weeks after
increasing activity and fiber and fluid intake.
The patient’s observations and medical history
help a primary care physician diagnose constipation.
The doctor uses his fingers to see if there is a hardened
mass in the abdomen, and may perform a rectal examination. Other diagnostic procedures include a barium
enema, which reveals blockage inside the intestine;
laboratory analysis of blood and stool samples for
internal bleeding or other symptoms of systemic disease; and a sigmoidoscopy (examination of the sigmoid
area of the colon with a flexible tube equipped with a
magnifying lens).
993

Constipation

Physical and psychological assessments and a
detailed history of bowel habits are especially important when an elderly person complains of constipation.

Treatment
If changes in diet and activity fail to relieve occasional constipation, an over-the-counter laxative may
be used for a few days. Preparations that soften stools
or add bulk (bran, psyllium) work more slowly but are
safer than Epsom salts and other harsh laxatives or
herbal laxatives containing senna (Cassia senna) or
buckthorn (Rhamnus purshianna), which can harm
the nerves and lining of the colon.
A woman who is pregnant should never use a
laxative. Neither should anyone who is experiencing
abdominal pain, nausea, or vomiting.
A warm-water or mineral oil enema can relieve
constipation, and a non-digestible sugar (lactulose) or
special electrolyte solution is recommended for adults
and older children with stubborn symptoms.
If a patient has an impacted bowel, the doctor
inserts a gloved finger into the rectum and gently
dislodges the hardened feces.

Alternative treatment
Initially, alternative practitioners will suggest that
the patient drink an adequate amount of water each
day (six to eight glasses), exercise on a regular basis,
and eat a diet high in soluble and insoluble fibers.
Soluble fibers include pectin, flax, and gums; insoluble
fibers include psyllium and brans from grains like
wheat and oats. Fresh fruits and vegetables contain
both soluble and insoluble fibers. Castor oil, applied
topically to the abdomen and covered by a heat source
(a heating pad or hot water bottle), can help relieve
constipation when used nightly for 20–30 minutes.
Acupressure
This needleless form of acupuncture is said to relax
the abdomen, ease discomfort, and stimulate regular
bowel movements when diet and exercise fail to do so.
After lying down, the patient closes his eyes and takes
a deep breath. For two minutes, he applies gentle
fingertip pressure to a point about two and one-half
inches below the navel.
Accupressure can also be applied to the outer
edges of one elbow crease and maintained for 30 seconds before pressing the crease of the other elbow.
This should be done three times a day to relieve
constipation.
994

Aromatherapy
Six drops of rosemary (Rosmarinus officinalis) and
six drops of thyme (Thymus spp.) diluted by 1 oz of
almond oil, olive oil, or another carrier oil can relieve
constipation when used to massage the abdomen.
Herbal therapy
A variety of herbal therapies can be useful in
the treatment of constipation. Several herbs, including chamomile (Matricaria recutita), dandelion
(Taraxacum mongolicum), and burdock (Arctium
lappa), act as bitters, stimulating the movement of
the digestive and excretory systems. There are also
‘‘laxative’’ herbs that assist with bowel movement.
Two of these are senna (Cassia senna) and buckthorn
(Rhamnus purshiana). These ‘‘laxative’’ herbs are
stronger acting on elimination than bitters and can
sometimes cause cramping (mixing them with a calming herb like fennel or caraway can help reduce cramping). Both senna and buckthorn are powerful herbs
that are best used with direction from an experienced
practitioner, since they can have adverse side effects
and the patient may become dependent on them.
Homeopathy
Homeopathy also can offer assistance with constipation. There are acute remedies for constipation
that can be found in one of the many home remedy
books on homeopathic medicine. A constitutional prescription also can help rebalance someone who is
struggling with constipation.
Massage
Massaging the leg from knee to hip in the morning, at night, and before trying to move the bowels is
said to relieve constipation. There is also a specific
Swedish massage technique that can help relieve
constipation.
Yoga
The knee-chest position, said to relieve gas and
stimulate abdominal organs, involves:


standing straight with arms at the sides



lifting the right knee toward the chest



grasping the right ankle with the left hand



pulling the leg as close to the chest as possible



holding the position for about eight seconds



repeating these steps with the left leg
GALE ENCYCLOPEDIA OF MEDICINE

Constipation

Transverse colon

Stool
Descending colon

Sigmoid colon
Rectum

Constipation is an acute or chronic condition in which bowel movements occur less often than usual or consist of hard, dry
stools that are painful or difficult to pass. (Illustration by Electronic Illustrators Group).

The cobra position, which can be repeated as
many as four time a day, involves:


lying on the stomach with legs together



placing the palms just below the shoulders, holding
elbows close to the body



inhaling, then lifting the head (face forward) and
chest off the floor



keeping the navel in contact with the floor



looking as far upward as possible



holding this position for three to six seconds



exhaling and lowering the chest

Prognosis
Changes in diet and exercise usually eliminate the
problem.

Prevention
Most Americans consume between 11–18 grams
of fiber a day. Consumption of 30 grams of fiber and
between six and eight glasses of water each day can
generally prevent constipation.
Thirty-five grams of fiber a day (an amount equal
to five servings of fruits and vegetables, and a large
bowl of high-fiber cereal) can relieve constipation.
GALE ENCYCLOPEDIA OF MEDICINE

Daily use of 500 mg vitamin C and 400 mg magnesium can prevent constipation. If symptoms do
occur, each dosage can be increased by 100 mg a day,
up to a maximum of 5,000 mg vitamin C and 1,000 mg
magnesium. Use of preventive doses should be
resumed after relief occurs, and vitamin C should be
decreased to the pre-diarrhea dosage if the patient
develops diarrhea.
Sitting on the toilet for 10 minutes at the same
time every day, preferably after a meal, can induce
regular bowel movements. This may not become effective for a few months, and it is important to defecate
whenever necessary.
Fiber supplements containing psyllium (Plantago
psyllium) usually become effective within about 48
hours and can be used every day without causing
dependency. Powdered flaxseed (Linium usitatissimum) works the same way. Insoluble fiber, like
wheat or oat bran, is as effective as psyllium but may
give the patient gas at first.
Resources
OTHER

‘‘Constipation.’’ ThriveOnline. March 15, 1998. <http://
thriveonline.oxygen.com>.

Maureen Haggerty
995

Contact dermatitis

Constitutional homeopathic remedies see
Homeopathic remedies, constitutional
prescribing
Consumption see Tuberculosis

I Contact dermatitis
Definition
Contact dermatitis is the name for any skin
inflammation that occurs when the skin’s surface
comes in contact with a substance originating outside
the body. There are two kinds of contact dermatitis,
irritant and allergic.

Description
Thousands of natural and man made substances
can cause contact dermatitis, which is the most common skin condition requiring medical attention and
the foremost source of work-related disease. Florists,
domestic workers, hairdressers, food preparers, and
employees in industry, construction, and health care
are the people most at risk of contracting work-related
contact dermatitis. Americans spend roughly $300
million a year in their quest for relief from contact
dermatitis, not counting the considerable sums
devoted by governments and businesses to regulating
and policing the use of skin-threatening chemicals in
the workplace. But exactly how many people suffer
from contact dermatitis remains unclear; a 1997 article
in the Journal of the American Medical Association
notes that figures ranging from 1% to 15% have
been put forward for Western industrial nations.

Causes and symptoms
Irritant contact dermatitis (ICD) is the more commonly reported of the two kinds of contact dermatitis,
anf is seen in about 80% of cases. It can be caused by
soaps, detergents, solvents, adhesives, fiberglass, and
other substances that are able to directly injure the
skin. Most attacks are slight and confined to the
hands and forearms, but can affect any part of
the body that comes in contact with an irritating substance. The symptoms can take many forms: redness,
itching, crusting, swelling, blistering, oozing, dryness,
scaliness, thickening of the skin, and a feeling of
warmth at the site of contact. In extreme cases, severe
blistering can occur and open sores can form. Jobs
that require frequent skin exposure to water, such as
996

hairdressing and food preparation, can make the skin
more susceptible to ICD.
Allergic contact dermatitis (ACD) results when
repeated exposure to an allergen (an allergy-causing
substance) triggers an immune response that inflames
the skin. Tens of thousands of drugs, pesticides, cosmetics, food additives, commercial chemicals, and
other substances have been identified as potential
allergens. Fewer than 30, however, are responsible
the majority of ACD cases. Common culprits include
poison ivy, poison oak, and poison sumac; fragrances
and preservatives in cosmetics and personal care products; latex items such as gloves and condoms; and
formaldehyde. Many people find that they are allergic
to the nickel in inexpensive jewelry. ACD is usually
confined to the area of skin that comes in contact with
the allergen, typically the hands or face. Symptoms
range from mild to severe and resemble those of ICD;
a patch test may be needed to determine which kind of
contact dermatitis a person is suffering from.

Diagnosis
Diagnosis begins with a physical examination and
asking the patient questions about his or her health
and daily activities. When contact dermatitis is suspected, the doctor attempts to learn as much as possible about the patient’s hobbies, workplace duties, use
of medications and cosmetics, etc.–anything that
might shed light on the source of the disease. In some
cases, an examination of the home or workplace is
undertaken. If the dermatitis is mild, responds well
to treatment, and does not recur, ordinarily the investigation is at an end. More difficult cases require patch
testing to identify the allergen.
Two methods of patch testing are currently used.
The most widely used method, the Finn chamber
method, employs a multiwell, aluminum patch. Each
well is filled with a small amount of the allergen being
tested and the patch is taped to normal skin on the
patient’s upper back. After 48 hours, the patch is
removed and an initial reading is taken. A second
reading is made a few days later. The second method
of patch testing involves applying a small amount of
the test substance to directly to normal skin and covering it with a dressing that keeps air out and keeps the
test substance in (occlusive dressing). After 48 hours,
the dressing is taken off to see if a reaction has
occurred. Identifying the allergen may require
repeated testing, can take weeks or months, and is
not always successful. Moreover, patch testing works
only with ACD, though it is considered an essential
step in ruling out ICD.
GALE ENCYCLOPEDIA OF MEDICINE

Antibiotics—Substances used against microorganisms that cause infection.
Corticosteroids—A group of anti-inflammatory
substances often used to treat skin conditions.
Immune response—The protective reaction by the
immune system against foreign antigens (substances that the body perceives as potentially dangerous). The immune system combats disease by
neutralizing or destroying antigens.

The abdomen of a male patient afflicted with contact dermatitis, triggered by an allergic reaction to a nickel belt buckle.
(Photograph by Dr. P. Marazzi, Custom Medical Stock Photo.
Reproduced by permission.)

Treatment
The best treatment for contact dermatitis is to
identify the allergen or irritating substance and avoid
further contact with it. If the culprit is, for instance, a
cosmetic, avoidance is a simple matter, but in some
situations, such as an allergy to an essential workplace
chemical for which no substitute can be found, avoidance may be impossible or force the sufferer to find
new work or make other drastic changes in his or her
life. Barrier creams and protective clothing such as
gloves, masks, and long-sleeved shirts are ways of
coping with contact dermatitis when avoidance is
impossible, though they are not always effective.
For the symptoms themselves, treatments in mild
cases include cool compresses and nonprescription
lotions and ointments. When the symptoms are severe,
corticosteroids applied to the skin or taken orally are
used. Contact dermatitis that leads to a bacterial skin
infection is treated with antibiotics.



burdock (Arctium lappa) minimizes inflammation
and boosts the immune system. It is taken internally
as a tea or tincture (a concentrated herbal extract
prepared with alcohol).



calendula (Calendula officinalis) is a natural antiseptic and anti-inflammatory agent. It is applied topically in a lotion, ointment, or oil to the affected area.



aloe (Aloe barbadensis) soothes skin irritations. The
gel is applied topically to the affected area.

A homeopath treating a patient with contact dermatitis will do a thorough investigation of the individual’s history and exposures before prescribing a
remedy. One homeopathic remedy commonly prescribed to relieve the itching associated with contact
dermatitis is Rhus toxicodendron taken internally three
to four times daily.
Poison ivy, poison oak, and poison sumac are
common culprits in cases of allergic contact dermatitis. Following exposure to these plants, rash development may be prevented by washing the area with soap
and water within 15 minutes of exposure. The leaves of
jewelweed (Impatiens spp.), which often grows near
poison ivy, may neutralize the poison-ivy allergen if
rubbed on the skin right after contact. Several topical
remedies may help relieve the itching associated with
allergic contact dermatitis, including the juice of plantain leaves (Plantago major); a paste made of equal
parts of green clay and goldenseal root (Hydrastis
canadensis); a paste made of salt, water, clay, and
peppermint (Mentha piperita) oil; and calamine lotion.

Alternative treatment
Herbal remedies have been used for centuries to
treat skin disorders including contact dermatitis. An
experienced herbalist can recommend the remedies
that will be most effective for an individual’s condition. Among the herbs often recommended are:
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
If the offending substance is promptly identified
and avoided, the chances of a quick and complete
recovery are excellent. Otherwise, symptom management–not cure–is the best doctors can offer. For some
997

Contact dermatitis

KEY TERMS

Contraception

people, contact dermatitis becomes a chronic and disabling condition that can have a profound effect on
employability and quality of life.

Types Of Contraceptives

Prevention
Avoidance of known or suspected allergens or
irritating substances is the best prevention. If avoidance is difficult, barrier creams and protective clothing
can be tried. Skin that comes in contact with an
offending substance should be thoroughly washed as
soon as possible.

Effectiveness

Predicted (%)

Actual (%)

Birth control pills
Condoms
Depo Provera
Diaphragm
IUDs
Norplant
Tubal sterilization
Spermicides
Vasectomy

99.9
98
99.7
94
99.2
99.7
99.8
97
99.9

97
88
99.7
82
97
99.7
99.6
79
99.9

Resources
PERIODICALS

Beltrani, Vincent S., and Vincent P. Beltrani. ‘‘Contact
Dermatitis.’’ Annals of Allergy, Asthma, and
Immunology 78 (February 1997): 160-75.

Howard Baker

Contact lenses see Eye glasses and contact
lenses
Continent urinary diversion see Urinary
diversion surgery
Continuous ambulatory electrocardiography
see Holter monitoring
Continuous positive airway see Inhalation
therapies

Birth control (contraception) is designed to interfere with the normal process and prevent the pregnancy that could result. There are different kinds of
birth control that act at different points in the process,
from ovulation, through fertilization, to implantation.
Each method has its own side effects and risks. Some
methods are more reliable than others.
There are more different types of birth control
available today than ever. They can be divided into a
few groups based on how they work. These groups
include:


Hormonal methods—These use medications (hormones) to prevent ovulation. Hormonal methods
include birth control pills (oral contraceptives),
Depo Provera injections, and Norplant.



Barrier methods—These methods work by preventing the sperm from getting to and fertilizing the egg.
Barrier methods include the condom, diaphragm, and
cervical cap. The condom is the only form of birth
control that also protects against sexually transmitted diseases, including HIV (the virus that causes
AIDS).



Spermicides—These medications kill sperm on contact. Most spermicides contain nonoxynyl-9.
Spermicides come in many different forms such as
jelly, foam, tablets, and even a transparent film. All
are placed in the vagina. Spermicides work best when
they are used at the same time as a barrier method.



Intrauterine devices—Intrauterine contraceptive
devices (IUDs) are inserted into the uterus, where
they stay from one to 10 years. An IUD prevents
the fertilized egg from implanting in the lining of
the uterus, and may have other effects as well.



Tubal sterilization—Tubal sterilization is a permanent
form of contraception for women. Each fallopian tube
is either tied or burned closed. The sperm cannot reach
the egg, and the egg cannot travel to the uterus.

I Contraception
Definition
Contraception (birth control) prevents pregnancy
by interfering with the normal process of ovulation,
fertilization, and implantation. There are different
kinds of birth control that act at different points in
the process.

Purpose
Every month, a woman’s body begins the process
that can potentially lead to pregnancy. An egg (ovum)
matures, the mucus that is secreted by the cervix (a
cylindrical-shaped organ at the lower end of the
uterus) changes to be more inviting to sperm, and the
lining of the uterus grows in preparation for receiving
a fertilized egg. Any woman who wants to prevent
pregnancy must use a reliable form of birth control.
998

GALE ENCYCLOPEDIA OF MEDICINE

Vasectomy—is the male form of sterilization, and
should also be considered permanent. In vasectomy,
the vas defrens, the tiny tubes that carry the sperm
into the semen, are cut and tied off. Thus, no sperm
can get into the semen.



A newer and somewhat controversial form of birth
control is emergency contraception. This type is used
after unprotected intercourse and sometimes is
referred to as the ‘‘morning-after pill’’.

Unfortunately, there is no perfect form of birth
control. Only abstinence (not having sexual intercourse) can protect against unwanted pregnancy with
100% reliability. The failure rates, which means the
rates of pregnancy, for most forms of birth control are
quite low. However, some forms of birth control are
more difficult or inconvenient to use than others. In
actual practice, the birth control methods that are
more difficult or inconvenient have much higher failure rates because they are not used regularly or as
prescribed.

Contraception



Various types of contraception. (Photo Researchers, Inc.
Reproduced by permissi)

Description
Most forms of birth control have one thing in
common. They are only effective if used faithfully.
Birth control pills will work only if taken every day;
the diaphragm is effective only if used during every
episode of sexual intercourse. The same is true for condoms and the cervical cap. Some methods automatically work every day. These methods include Depo
Provera, Norplant, the IUD, and tubal sterilization.
There are many different ways to use birth control. They can be divided into several groups:


By mouth (oral)—Birth control pills must be taken
by mouth every day.



Injected—Depo Provera is a hormonal medication
that is given by injection every three months.



Implanted—Norplant is a long-acting hormonal
form of birth control that is implanted under the
skin of the upper arm.



Vaginal—Spermicides and barrier methods work in
the vagina.



Intra-uterine—The IUD is inserted into the uterus.



Surgical—Tubal sterilization is a form of surgery. A
doctor must perform the procedure in a hospital or
surgical clinic. Many women need general
anesthesia.

The methods of birth control differ from each
other in the timing of when they are used. Some methods of birth control must be used specifically at the
GALE ENCYCLOPEDIA OF MEDICINE

A variety of intrauterine contraceptive devices. The probability of a pregnancy for year of use is about 2 to 3%. IUDs made
with copper coils should be replaced every 3 to 5 years. (Photo
Researchers, Inc. Reproduced by permission.)

time of sexual intercourse (condoms, diaphragm, cervical cap, spermicides). Emergency contraception
must be started as soon as possible after intercourse
and no more than 72 hours after. All other methods
of birth control (hormonal methods, IUDs, tubal
999

Contractures

Risks

KEY TERMS
Fallopian tubes—The thin tubes that connect the
ovary to the uterus. Ova (eggs) travel from the ovary
to the uterus. If the egg has been fertilized, it can
implant in the uterus.
Fertilization—The joining of the sperm and the
egg; conception.

Many methods of birth control have side effects.
Knowing the side effects can help a woman to determine which method of birth control is right for her.


Hormonal methods—The hormones in birth control
pills, Depo Provera, and Norplant can cause changes
in menstrual periods, changes in mood, weight gain,
acne, and headaches. In addition, it may take many
months to begin ovulating again once a woman stops
using Depo Provera or Norplant.



Barrier methods—A woman must insert the diaphragm in just the right way to be sure that it
works properly. Some women get more urinary
tract infections if they use a diaphragm. This is
because the diaphragm can press against the urethra,
the tube that connects the bladder to the outside.



Spermicides—Some women and men are allergic to
spermicides or find them irritating to the skin.



IUD—The IUD is a foreign body that stays inside
the uterus, and the uterus tries to get it out. A woman
may have heavier menstrual periods and more menstrual cramping with an IUD in place.



Tubal sterilization—Some women report increased
menstrual discomfort after tubal ligation. It is not
known if this is related to the tubal ligation itself.

Implantation—The process in which the fertilized
egg embeds itself in the wall of the uterus.
Ovulation—The release of an egg (ovum) from the
ovary.

sterilization) must be working all the time to provide
protection.

Precautions
There are risks associated with certain forms of
birth control. Some of the risks of each method are
listed below:


Birth control pills—The hormone (estrogen) in birth
control pills can increase the risk of heart attack in
women over 35, particularly those who smoke.
Certain women cannot use birth control pills.



IUD—The IUD can increase the risk of serious pelvic infection. The IUD can also injure the uterus by
poking into or through the uterine wall. Surgery
might be needed to fix this.



Tubal sterilization—‘‘Tying the tubes’’ is a surgical
procedure and has all the risks of any other surgery,
including those associated with anesthesia, as well as
infection and bleeding.



Emergency contraceptive pills should not be used
regularly for birth control. They can interrupt the
menstrual cycle and are not 100% effective. If the
emergency contraception fails, an ectopic pregnancy
can occur.

There is no perfect form of birth control. Every
method has a small failure rate and side effects. Some
methods carry additional risks. However, every
method of birth control can be effective if used
properly.
Resources
PERIODICALS

‘‘Contraception; Overview.’’ NWHRC Health Center –
Contraception March 9, 2004.
‘‘Ectopic Pregnancy Is a Possibility When Emergency
Contraception Fails.’’ Health & Medicine Week March
15, 2004: 222.

Amy B. Tuteur, MD
Teresa G. Odle

Preparation
No specific preparation is needed before using
contraception. However, a woman must be sure that
she is not already pregnant before using a hormonal
method or having an IUD placed.

I Contractures
Definition

Aftercare
No aftercare is needed.
1000

Contractures are the chronic loss of joint motion
due to structural changes in non-bony tissue. These
GALE ENCYCLOPEDIA OF MEDICINE

Description
Contractures can occur at any joint of the body. This
joint dysfunction may be a result of immobilization from
injury or disease; nerve injury, such as spinal cord damage
and stroke; or muscle, tendon, or ligament disease.

KEY TERMS
Mobilization—Making movable, restoring the
power of motion in a joint. Movement which
increases joint mobility.
Muscle tone —Also termed tonus; the normal state
of balanced tension in the tissues of the body, especially the muscles.

Causes and symptoms
There are a number of pathologies and diseases
that can lead to joint contractures. The primary causes
resulting in a joint contraction are muscle imbalance,
pain, prolonged bed rest, and immobilization. Because
of the frequency of fractures and surgery, immobilization is the most frequent cause of joint contractures.
Symptoms include a significant loss of motion to any
specific joint that results in immobility. If the contracture is of a significant degree, pain can result even
without any voluntary joint movement.

surgery of joints. Continuous passive motion
machines (CPM) are specifically adjusted to each individual’s need. This method is administered within the
first 24–72 hours after the injury or surgery. The joint
is mechanically moved through the patient’s tolerable
motion. CPM machines have been proved to accelerate the return motion process, allowing patients more
function in less time.
Casting or splinting

Diagnosis
Manual testing of joint mobility by a healthcare
professional skilled in joint mobilization techniques
(e.g., a physical therapist) will identify indications of
restricted structures within the joint. Measuring the
motion of the joint with a device termed a ‘‘goniometer’’
can be useful if the decrease of motion can be shown to
be a proven result of a joint contracture. X rays can be of
some benefit in the diagnosis of contractures, because a
visible decrease in joint space may indicate a tight, contracted joint. Most physicians will make the diagnosis
after a thorough physical examination involving physical
and manual testing of the joint motion.

Treatment
Manual techniques
Joint mobilization and stretching of soft tissues
is a common technique used to increase joint elasticity. Structures are stretched in similar directions to
those which take place upon normal joint motion.
Some healthcare professionals may use some form
of heat prior to the stretching and mobilization. If
appropriate, exercise may follow manual techniques
to help maintain the additional motion achieved.
Mechanical techniques
Devices known as continuous passive motion
machines are very popular, especially following
GALE ENCYCLOPEDIA OF MEDICINE

Casting or splinting techniques are used to provide a constant stretch to the soft tissues surrounding
a joint. It is most effective when used to increase
motion of a joint from prolonged immobilization. It
is also popular for treating contractures resulting
from an increase in muscle tone from nerve injury.
After an initial holding cast is applied for seven to 10
days, a series of positional casts are applied at weekly
intervals. Before the application of each new cast, the
joint is moved as much as can be tolerated by the
patient, and measured by a goniometer. When as
much motion as possible is obtained after stretching,
another final cast is applied to maintain the newly
acquired motion.
Surgery
In some cases, the contracture may be severe and
not respond to conservative treatment. In this event,
manipulation of the joint under a general anesthesia
may be necessary.

Alternative treatment
In some areas of the body, chiropractic techniques
have been found to be useful to improve motion.
Massage therapy can be beneficial by promoting additional circulation to joint structures, causing better
elasticity. Yoga can help prevent as well as rehabilitate
a contracture and can facilitate the return of joint
mobility.
1001

Contractures

non-bony tissues include muscles, ligaments, and
tendons.

Cooling treatments

Prognosis
Prognosis of contractures will depend upon the
cause of the contracture. In general, the earlier the
treatment for the contracture begins, the better the
prognosis.

Prevention
Prevention of contractures and deformities from
spinal cord injury, fracture, and immobilization is
achieved through a program of positioning, splinting
if appropriate, and range-of-motion exercises either
manually or mechanically aided. These activities should
be started as early as possible for optimal results.
Resources
ORGANIZATIONS

The American College of Rheumatology. 1800 Century
Place, Suite 250, Atlanta, GA 30345. (404) 633-3777.
<http://www.rheumatology.org>.
American Physical Therapy Association. 1111 North
Fairfax St., Alexandria, VA 22314. (800) 999-2782.
<https://www.apta.org>.

sprains, bruises, burns, eye injuries, and muscle spasms
to help alleviate the resulting swelling, pain, and discoloration of the skin.
Cooling treatments slow chemical reactions
within the body. For this reason, cooling tissues
below normal temperature (98.6  F/37  C) can prevent
injury from inadequate oxygen or nutrition. Cold
water drowning victims suffering from hypothermia
(cooling of the body below its normal temperature)
have been successfully resuscitated after long periods
underwater without medical complications because of
this effect. For the past 40 years, heart surgeons have
been experimenting with hypothermia to protect
tissues from lack of blood circulation during an
operation. Neurosurgeons are also working with
hypothermia to protect the very sensitive brain tissues
during periods of absent or reduced blood flow.

Description
Depending on the medical need, various cooling
methods are used.


Cold packs and ice bags are placed on a localized site
and provide topical relief. These compresses should
be covered with a waterproof material to protect the
skin. Repeated treatments produce the desired pain
and swelling relief.



Cold treatments are placed on the groin and under
the arms to treat hyperthermia. Treatments are
refreshed periodically until the appropriate temperature is attained.



A tepid sponge bath relieves fever without cooling
the body too fast. Eighty degrees Fahrenheit is still
20  F below body temperature and yet warm enough
not to drive blood from the skin, thereby preventing
the cooling from getting to the body’s core. Limbs
are bathed first and then the chest, abdomen, back,
and buttocks.



Perfusion of isolated regions like the brain by using
cooled blood is an experimental treatment, offering
promising results for the treatment of stroke.

Jeffrey P. Larson, RPT

Conversion disorder see Somatoform
disorders
Cooley’s anemia see Thalassemia

I Cooling treatments
Definition
Cooling treatments lower body temperature in
order to relieve pain, swelling, constriction of blood
vessels, and to decrease the liklihood of cellular damage
by slowing the metabolism. Sponge baths, cold compresses, and cold packs are all wet cooling treatments.
Dry treatments, such as ice bags and chemical cold
packs, are also used to lower body temperature.

Preparation
Purpose
The most common reason for cooling a body is
fever or hyperthermia (extremely high fever). The
body can sustain temperatures up to 104  F (40  C)
with relative safety; however, when temperatures rise
above 104  F (40  C), damage to the brain, muscles,
blood, and kidneys is increasingly likely. Cooling
treatments are also applied immediately following
1002

Topical treatments are prepared with ice, cold
water (59  F/15  C), and chemical cold packs. Tepid
baths should be 80–93  F (26.7–34  C).

Risks
Small children, adults with circulation problems,
and the elderly are all at risk of tissue damage. Rapid
GALE ENCYCLOPEDIA OF MEDICINE



virus infections



collagen-vascular diseases



mismatched blood transfusions

Resources



Rh incompatibility between a mother and fetus.
(erythroblastosis fetalis)

PERIODICALS

Plattner, O., et al. ‘‘Efficacy of Intraoperative Cooling
Methods.’’ Anesthesiology 87 (November 1997):
1089-1095.

J. Ricker Polsdorfer, MD

I Coombs’ tests
Definition
Coombs’ tests are blood tests that identify the
causes of anemia.

Purpose
Anemia, which literally means no blood, refers
to blood with abnormally low oxygen-carrying capacity. The hemoglobin in red blood cells carries oxygen. One of the many causes of anemia is destruction
of red blood cells, a process called hemolysis (hemo
means blood and lysis means disintegration). A simple blood count detects anemia. Even the test done
before a blood donation can identify anemia. To
detect hemolysis requires other tests. The Coombs’
tests are conducted in order to determine the cause of
anemia.
One characteristic of hemolysis is the autoimmune response against the body’s red blood cells.
Instead of protecting the body from outside agents,
the immune system attacks parts of its own body with
a deluge of antibodies. Autoimmunity is thought to
be the cause of many collagen-vascular diseases,
including rheumatoid arthritis and systemic lupus
erythematosus. It is also the cause of the autoimmune
hemolytic anemias. The Coombs’ tests detect the
antibodies responsible for the destruction of the red
blood cells.
Causes of autoimmune hemolytic anemia include:


drugs such as penicillin, methyldopa (lowers blood
pressure), and quinidine (treats heart rhythm
disturbances)



cancers of the lymph system–Hodgkin’s disease and
lymphomas

GALE ENCYCLOPEDIA OF MEDICINE

Many times the cause cannot be identified.

Description
There are two Coombs’ tests. A direct Coombs’
test detects the two different antigens that might
induce hemolysis in the patient’s red blood cells.
An indirect Coombs’ test looks for antibodies to
someone else’s red blood cells in the patient’s
serum (the blood without the cells). Combining
the two tests gives clues to the origin of the
hemolysis.

Preparation
No preparation is needed for this test. It will
probably be among the second or third set of blood
tests done after anemia is diagnosed and there is a
suspicion that its cause is hemolysis.

Aftercare
Coombs’ tests are done on blood that is drawn
from the arm.

Risks
Taking blood for testing is the most common
medical procedure performed. The worst complication is a bruise at the site of the puncture or punctures.
It is extremely rare for the needle to injure an important structure such as an artery or a nerve.

Normal results
If the Coombs’ tests are negative, the anemia is
unlikely to be autoimmune, and the hematologist will
have to search elsewhere for a cause.

Abnormal results
If the test is positive, the antigens that react will
narrow the search for a cause. Coombs’ tests are
also done for blood transfusion reactions to determine why the transfused blood did not match, and
when there is a chance a newborn may have an Rh
problem.
1003

Coombs’ tests

cooling causes chills, which in effect raise the body’s
temperature by raising its metabolism. Blood clots may
form from thickened blood caused by the temperature
change.

Cor pulmonale

KEY TERMS
Antibody—A protein made by the immune system
and used as a weapon against foreign invaders in
the body.
Antigen—The chemical that stimulates an immune
response.
Anemia—Reduced oxygen-carrying capacity of the
blood, due to too little hemoglobin or too few red
blood cells.
Collagen-vascular disease—Various diseases
inflaming and destroying connective tissue.
Hematologist—Physician who specializes in diseases of the blood.
Hemoglobin—The red pigment in blood that carries oxygen.
Hemolysis—Breaking apart red blood cells.
Rh—A blood typing group, like the ABO system.
When a mother is Rh negative and her baby is Rh
positive, she may develop antibodies to the baby’s
blood that will cause it to hemolyze.

Resources
BOOKS

Rosse, Wendell, and H. Franklin Bunn. ‘‘Hemolytic
Anemias and Acute Blood Loss.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony S.
Fauci, et al. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Coordination tests see Balance and coordination tests
COPD see Emphysema; Chronic obstructive
lung disease
Copper deficiency see Mineral deficiency
Copper excess see Wilson’s disease

I Cor pulmonale
Definition
Cor pulmonale is an increase in bulk of the right
ventricle of the heart, generally caused by chronic
1004

diseases or malfunction of the lungs. This condition
can lead to heart failure.

Description
Cor pulmonale, or pulmonary heart disease,
occurs in 25% of patients with chronic obstructive
pulmonary disease (COPD). In fact, about 85% of
patients diagnosed with cor pulmonale have COPD.
Chronic bronchitis and emphysema are types of
COPD. High blood pressure in the blood vessels of
the lungs (pulmonary hypertension) causes the enlargement of the right ventricle. In addition to COPD, cor
pulmonale may also be caused by lung diseases, such
as cystic fibrosis, pulmonary embolism, and pneumoconiosis. Loss of lung tissue after lung surgery or certain chest-wall disturbances can produce cor
pulmonale, as can neuromuscular diseases, such as
muscular dystrophy. A large pulmonary thromboembolism (blood clot) may lead to acute cor pulmonale.

Causes and symptoms
Any respiratory disease or malfunction that
affects the circulatory system of the lungs may lead
to cor pulmonale. These circulatory changes cause the
right ventricle to compensate for the extra work
required to pump blood through the lungs. The right
ventricle has thin walls and is crescent-shaped. The
resulting pressure causes the right ventricle to dilate
and bulge, eventually leading to its failure.
Cor pulmonale should be expected in any patient
with COPD and other respiratory or neuromuscular
diseases. Initial symptoms of cor pulmonale may actually reflect those of the underlying disease. These may
include chronic coughing, wheezing, weakness, fatigue,
and shortness of breath. Edema (abnormal buildup of
fluid), weakness, and discomfort in the upper chest
may be evident in cor pulmonale.

Diagnosis
An electrocardiograph (EKG) will show signs such
as frequent premature contractions in the atria or ventricles. Chest x rays may show enlargement of the right
descending pulmonary artery. This sign, along with an
enlarged main pulmonary artery, indicates pulmonary
artery hypertension in patients with COPD. Magnetic
resonance imaging (MRI) is often the preferred method
of diagnosis for cor pulmonale because it can clearly
show and measure volume of the pulmonary arteries.
Other tests used to support a diagnosis of cor pulmonale may include arterial blood gas analysis, pulmonary
function tests, and hematocrit.
GALE ENCYCLOPEDIA OF MEDICINE

Ventricle—A cavity, as in the brain or heart. The
right ventricle of the heart drives blood from the
heart into the pulmonary artery, which supplies
blood to the lungs.

Treatment
Treatment of cor pulmonale is aimed at increasing
a patient’s exercise tolerance and improving oxygen
levels of the arterial blood. Treatment is also aimed at
the underlying condition that is producing cor pulmonale. Common treatments include antibiotics for
respiratory infection; anticoagulants to reduce the
risk of thromboembolism; and digitalis, oxygen, and
phlebotomy to reduce red blood cell count. A low-salt
diet and restricted fluids are often prescribed.

National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Teresa Odle

Cori’s disease see Glycogen storage diseases
Corkscrew esophagus see Diffuse
esophageal spasm

I Corneal abrasion
Definition
A corneal abrasion is a worn or scraped-off area
of the outer, clear layer of the eye (cornea).

Description
Alternative treatment
Co-management of the patient with cor pulmonale should be coordinated between the medical doctor and the alternative practitioner. The first step in
treatment is to determine the cause of the condition
and to evaluate all organ systems of the body. Dietary
considerations, for example, a low-salt diet and
reduced fluid intake aimed at reducing the edema
associated with cor pulmonale, can be supportive
aspects of treatment.

The cornea is the clear, dome-shaped outer area of
the eye. It lies in front of the colored part of the eye
(iris) and the black hole in the iris (pupil). The outermost layer of the eyeball consists of the cornea and the
white part of the eye (sclera). A corneal abrasion is
basically a superficial cut or scrape on the cornea. A
corneal abrasion is not as serious as a corneal ulcer,
which is generally deeper and more severe than an
abrasion.

Causes and symptoms
Prognosis
The prognosis for cor pulmonale is poor, particularly because it occurs late in the process of serious
disease.

A corneal abrasion is usually the result of direct
injury to the eye, often from a fingernail scratch,
makeup brushes, contact lenses, foreign body, or
even twigs. Patients often complain of feeling a foreign
body in their eye, and they may have pain, sensitivity
to light, or tearing.

Prevention
Cor pulmonale is best prevented by prevention of
COPD and other irreversible diseases that lead to
heart failure. Smoking cessation is critically important. Carefully following the recommended course of
treatment for the underlying disease may help prevent
cor pulmonale.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Ophthalmologists and optometrists, who treat eye
disorders, are well qualified to diagnose corneal abrasions. The doctor will check the patient’s vision (visual
acuity) in both eyes with an eye chart. A patient history will also be taken, which may help to determine
the cause of the abrasion. A slit lamp, which is basically a microscope and light source, will allow the
doctor to see the abrasion. Fluorescein, a yellow dye,
may be placed into the eye to determine the extent of
the abrasion. The fluorescein will temporarily stain the
affected area.
1005

Corneal abrasion

KEY TERMS

Corneal transplantation

KEY TERMS
Abrasion—An area of the body whose surface has
been worn away by some abnormal process.
Cornea—The transparent structure on the front part
of the eye.
Recurrent corneal erosion (RCE) —Repeated erosion of the cornea. May be a result of inadequate
healing of a previous abrasion.
Slit lamp—An instrument used to examine the front
of the eye.

Treatment
The cornea has a remarkable ability to heal itself,
so treatment is designed to minimize complications. If
the abrasion is very small, the doctor might just suggest an eye lubricant and a follow-up visit the next day.
A very small abrasion should heal in one to two days;
others usually in one week. However, to avoid a possible infection, an antibiotic eye drop may be prescribed. Sometimes additional eye drops may make
the eye feel more comfortable. Depending upon the
extent of the abrasion, some doctors may patch the
affected eye. It is very important to go for the followup checkup to make sure an infection does not occur.
Use of contact lenses should not be resumed without
the doctor’s approval.

A close-up view of an abrasion on patient’s cornea.
(Photograph by Dennis R. Cain, CRA, Custom Medical Stock
Photo. Reproduced by permission.)

lead to an abrasion, so patients should go for their
prescribed checkups.
Resources
ORGANIZATIONS

American Academy of Family Physicians. 8880 Ward
Parkway, Kansas City, MO 64114. (816) 333-9700.
<http://www.aafp.org>.

Prognosis
In typical cases, the prognosis is good. The cornea
will heal itself, usually within several days. A very deep
abrasion may lead to scarring. If the abrasion does not
heal properly, a recurrent corneal erosion (RCE) may
result months or even years later. The symptoms are
the same as for an abrasion (e.g., tearing, foreign body
sensation, and blurred vision), but it will keep occurring. Similar or additional treatment for the RCE may
be necessary.

Prevention
Everyone should wear eye protection whenever
this is recommended. This should be standard practice
when using power tools and playing certain sports.
Goggles should even be worn when mowing the
lawn, because a twig can be thrown upward toward
the face. Contact lens wearers should be careful to
follow their doctors’ instructions on caring for and
wearing their lenses. Ill-fitting or dirty lenses could
1006

Richard H. Lampert

Corneal infection see Keratitis
Corneal keratoplasty see Corneal
transplantation

I Corneal transplantation
Definition
In corneal transplant, also known as keratoplasty,
a patient’s damaged cornea is replaced by the cornea
from the eye of a human cadaver. This is the single
most common type of human transplant surgery and
has the highest success rate. Eye banks acquire and
store eyes from donor individuals largely to supply the
need for transplant corneas.
GALE ENCYCLOPEDIA OF MEDICINE

Corneal transplantation

Purpose
Corneal transplant is used when vision is lost in an
eye because the cornea has been damaged by disease or
traumatic injury. Some of the disease conditions that
might require corneal transplant include the bulging
outward of the cornea (keratoconus), a malfunction of
the inner layer of the cornea (Fuchs’ dystrophy), and
painful swelling of the cornea (pseudophakic bullous
keratopathy). Some of these conditions cause cloudiness of the cornea; others alter its natural curvature,
which can also reduce the quality of vision.
Injury to the cornea can occur because of chemical
burns, mechanical trauma, or infection by viruses,
bacteria, fungi, or protozoa. The herpes virus produces one of the more common infections leading to
corneal transplant.
Surgery would only be used when damage to the
cornea is too severe to be treated with corrective
lenses. Occasionally, corneal transplant is combined
with other types of eye surgery (such as cataract
surgery) to solve multiple eye problems in one
procedure.

Precautions
Corneal transplant is a very safe procedure that
can be performed on almost any patient who would
benefit from it. Any active infection or inflammation
of the eye usually needs to be brought under control
before surgery can be performed.

Description
The cornea is the transparent layer of tissue at the
very front of the eye. It is composed almost entirely of
a special type of collagen. It normally contains no
blood vessels, but because it contains nerve endings,
damage to the cornea can be very painful.
In a corneal transplant, a disc of tissue is
removed from the center of the eye and replaced by
a corresponding disc from a donor eye. The circular
incision is made using an instrument called a trephine. In one form of corneal transplant (penetrating
keratoplasty), the disc removed is the entire thickness of the cornea and so is the replacement disc.
Over 90% of all corneal transplants in the United
States are of this type. In lamellar keratoplasty, on
the other hand, only the outer layer of the cornea is
removed and replaced.
The donor cornea is attached with extremely fine
sutures. Surgery can be performed under anesthesia
that is confined to one area of the body while the
GALE ENCYCLOPEDIA OF MEDICINE

A corneal transplant in progress. (Photograph by Chet
Szymecki, Phototake NYC. Reproduced by permission.)

patient is awake (local anesthesia) or under anesthesia
that places the entire body of the patient in a state
of unconsciousness (general anesthesia). Surgery
requires 30–90 minutes.
Over 40,000 corneal transplants are performed in
the United States each year. Medicare reimbursement
for a corneal transplant in one eye was about $1,200 in
1997.
A less common but related procedure called epikeratophakia involves suturing the donor cornea
directly onto the surface of the existing host cornea.
The only tissue removed from the host is the extremely
thin epithelial cell layer on the outside of the host
cornea. There is no permanent damage to the host
cornea, and this procedure can be reversed. It is
usually employed in children. In adults, the use of
contact lenses can usually achieve the same goals.

Preparation
No special preparation for corneal transplant is
needed. Some eye surgeons may request the patient
have a complete physical examination before surgery.
The patient may also be asked to skip breakfast on the
day of surgery.

Aftercare
Corneal transplant is often performed on an outpatient basis, although some patients need brief hospitalization after surgery. The patient will wear an eye
patch at least overnight. An eye shield or glasses must
be worn to protect the eye until the surgical wound has
healed. Eye drops will be prescribed for the patient to
use for several weeks after surgery. These drops
include antibiotics to prevent infection as well as
1007

Corneal transplantation

KEY TERMS
Cadaver—The human body after death.
Cataract—A condition of cloudiness of the lens of
the eye.
Cornea—The transparent layer of tissue at the very
front of the eye.
Corticosteroids—Synthetic hormones widely used
to fight inflammation.
Epikeratophakia—A procedure in which the donor
cornea is attached directly onto the host cornea.
Epithelial cells—Cells that form a thin surface coating on the outside of a body structure.
Fibrous connective tissue—Dense tissue found in
various parts of the body containing very few living
cells.
Fuchs’ dystrophy—A hereditary disease of the
inner layer of the cornea. Treatment requires penetrating keratoplasty. The lens of the eye may also be
affected and require surgical replacement at the
same time as the cornea.
Glaucoma—A vision defect caused when excessive fluid pressure within the eye damages the
optic nerve.
Histocompatibility antigens—Proteins scattered
throughout body tissues that are unique for almost
every individual.
Keratoconus—An eye condition in which the cornea bulges outward, interfering with normal vision.
Usually both eyes are affected.
Pseudophakic bullous keratopathy—Painful swelling of the cornea occasionally occurring after surgery to implant an artificial lens in place of a lens
affected by cataract.
Retinal detachment—A serious vision disorder in
which the light-detecting layer of cells inside the
eye (retina) is separated from its normal support
tissue and no longer functions properly.
Trephine—A small surgical instrument that is
rotated to cut a circular incision.

corticosteroids to reduce inflammation and prevent
graft rejection.
For the first few days after surgery, the eye may
feel scratchy and irritated. Vision will be somewhat
blurry for as long as several months.

Sutures are often left in place for six months, and
occasionally for as long as two years.

Risks
Corneal transplants are highly successful, with
over 90% of operations in United States achieving
restoration of sight. However, there is always some
risk associated with any surgery. Complications that
can occur include infection, glaucoma, retinal detachment, cataract formation, and rejection of the donor
cornea.
Graft rejection occurs in 5–30% of patients, a
complication possible with any procedure involving
tissue transplantation from another person (allograft).
Allograft rejection results from a reaction of the
patient’s immune system to the donor tissue. Cell surface proteins called histocompatibility antigens trigger
this reaction. These antigens are often associated with
vascular tissue (blood vessels) within the graft tissue.
Since the cornea normally contains no blood vessels, it
experiences a very low rate of rejection. Generally,
blood typing and tissue typing are not needed in corneal
transplants, and no close match between donor and
recipient is required. Symptoms of rejection include
persistent discomfort, sensitivity to light, redness, or a
change in vision.
If a rejection reaction does occur, it can usually be
blocked by steroid treatment. Rejection reactions may
become noticeable within weeks after surgery, but may
not occur until 10 or even 20 years after the transplant.
When full rejection does occur, the surgery will usually
need to be repeated.
Although the cornea is not normally vascular,
some corneal diseases cause vascularization (the
growth of blood vessels) into the cornea. In patients
with these conditions, careful testing of both donor
and recipient is performed just as in transplantation of
other organs and tissues such as hearts, kidneys, and
bone marrow. In such patients, repeated surgery is
sometimes necessary in order to achieve a successful
transplant.
Cornea donors are carefully screened. Individuals
with infectious diseases are not accepted as donors.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.

Victor Leipzig, PhD
1008

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I Corneal ulcers
Definition
The cornea, the clear front part of the eye
through which light passes, is subject to many infections and to injury from exposure and from foreign
objects. Infection and injury cause inflammation of
the cornea–a condition called keratitis. Tissue loss
because of inflammation produces an ulcer. The
ulcer can either be centrally located, thus greatly
affecting vision, or peripherally located. There are
about 30,000 cases of bacterial corneal ulcers in the
United States each year.

Description
The most common cause of corneal ulcers is
germs, but most of them cannot invade a healthy
cornea with adequate tears and a functioning eyelid.
They gain access because injury has impaired these
defense mechanisms. A direct injury from a foreign
object inoculates germs directly through the outer
layer of the cornea, just as it does to the skin. A caustic
chemical can inflame the cornea by itself or so damage
it that germs can invade. Improper use of contact
lenses has become a common cause of corneal injury.
Eyelid or tear function failure is the other way to make
the eye vulnerable to infection. Tears and the eyelid
together wash the eye and prevent foreign material
from settling in. Tears contain enzymes and other
substances to help protect against infection. Certain
diseases dry up tear production, leaving the cornea dry
and defenseless. Other diseases paralyze or weaken the
eyelids so that they cannot effectively protect and
cleanse the eyes.

Causes and symptoms
Viruses, bacteria, fungi, and a protozoan called
Acanthamoeba can all invade the cornea and damage it
under suitable conditions.


Bacteria from a common conjunctivitis (pink eye)
rarely spread to the cornea, but can if untreated.



Fecal bacteria are more likely to be able to infect the
cornea.



A bacterium called Pseudomonas aeruginosa, which
can contaminate eyedrops, is particularly able to
cause corneal infection.



A group of incomplete bacteria known as Chlamydia
can be transmitted to the eye directly by flies or dirty
hands. One form of chlamydial infection is the

GALE ENCYCLOPEDIA OF MEDICINE



Other sexually transmitted diseases–for example,
syphilis–can affect the cornea.

The most common viruses to damage the cornea
are adenoviruses and herpes viruses. Viral and fungal
infections are often caused by improper use of topical
corticosteroids. If topical corticosteroids are used in a
patient with the herpes simplex keratitis, the ulcer can
get much worse and blindness could result.
Symptoms are obvious. The cornea is intensely
sensitive, so corneal ulcers normally produce severe
pain. If the corneal ulcer is centrally located, vision is
impaired or completely absent. Tearing is present and
the eye is red. It hurts to look at bright lights.

Diagnosis
The doctor will take a case history to try to determine the cause of the ulcer. This can include improper
use of contact lenses; injury, such as a scratch from a
twig; or severe dry eye. An instrument called a slit
lamp will be used to examine the cornea. The slit
lamp is a microscope with a light source that magnifies
the cornea, allowing the extent of the ulcer to be seen.
Fluorescein, a yellow dye, may be used to illuminate
further detail. If a germ is responsible for the ulcer,
identification may require scraping samples directly
from the cornea, conjunctiva, and lids, and sending
them to the laboratory.

Treatment
A corneal ulcer needs to be treated aggressively, as
it can result in loss of vision. The first step is to eliminate
infection. Broad spectrum antibiotics will be used
before the lab results come back. Medications may
then be changed to more specifically target the cause
of the infection. A combination of medications may be
necessary. Patients should return for their follow-up
visits so that the doctor can monitor the healing process. The cornea can heal from many insults, but if it
remains scarred, corneal transplantation may be necessary to restore vision. If the corneal ulcer is large,
hospitalization may be necessary.

Prognosis
Treated early enough, corneal infections will
usually resolve, perhaps even without the formation
of an ulcer. However, left untreated, infections can
1009

Corneal ulcers

leading cause of blindness in developing countries
and is known as Egyptian ophthalmia or trachoma.
Another type of Chlamydia causes a sexually transmitted disease.

Corns and calluses

a risk than contacts for overnight wear (extended
wear). Organisms have been cultured from contact
lens cases, so the cases should be rinsed in hot water
and allowed to air dry. Cases should be replaced every
three months. Patients should follow their doctors’
schedules for replacement of the contacts.

A close-up view of an ulcer on cornea. (Custom Medical Stock
Photo. Reproduced by permission.)

KEY TERMS
Fluorescein—A fluorescent chemical used to
examine the cornea.
Germ—A disease-causing microorganism.
Inflammation—The body’s reaction to irritation.
Topical corticosteroids—Cortisone and related
drugs used on the skin and in the eye, usually for
allergic conditions.

lead to ulcers and the corneal ulcer can result in scarring or perforation of the cornea. Other problems may
occur as well, including glaucoma. Patients with certain systemic diseases that impede healing (such as
diabetes mellitus or rheumatoid arthritis) may need
more aggressive treatment. The later the treatment,
the more damage will be done and the more scarring
will result. Corneal transplant is standard treatment
with a high probability of success.

Eye protection in the workplace, or wherever tiny
particles are flying around, is essential. Ultraviolet
(UV) coatings on glasses or sunglasses can help protect the eyes from the sun’s rays. Goggles with UV
protection should be worn when skiing or in suntanning salons to protect against UV rays. Prompt attention to any red eye should prevent progressive
damage.
For people with inadequate tears, use of artificial
tears eyedrops will prevent damage from drying.
Eyelids that do not close adequately may temporarily
have to be sewn shut to protect the eye until more
lasting treatment can be instituted.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://
www.preventblindness.org>.

J. Ricker Polsdorfer, MD

I Corns and calluses
Definition

Prevention
Attentive care of contact lenses will greatly reduce
the incidence of corneal damage and ulceration.
Germs that cause no problems in the mouth or on
the hands can damage the eye, so contact lens wearers
must wash their hands before touching their lenses and
must not use saliva to moisten them. Tap water should
not be used to rinse the lenses. Contacts should be
removed whenever there is irritation and left out
until the eyes are back to normal. It is not advisable
to wear contact lenses while swimming or in hot tubs.
Daily wear contact lenses have been found to be less of
1010

A corn is a small, painful, raised bump on the
outer skin layer. A callus is a rough, thickened patch
of skin.

Description
Corns and calluses are one of the three major foot
problems in the United States. The other two are foot
infections and toenail problems. Corns and calluses
affect about 5% of the population.
Corns usually appear on non-weight-bearing
areas like the outside of the little toe or the tops of
GALE ENCYCLOPEDIA OF MEDICINE

Corns and calluses

other toes. Women have corns more often than men,
probably because women wear high-heeled shoes and
other shoes that do not fit properly. Corns have hard
cores shaped like inverted pyramids. Sharp pain occurs
whenever downward pressure is applied, and a dull
ache may be felt at other times.
Calluses occur most often on the heels and balls of
the feet, the knees, and the palms of the hands.
However, they can develop on any part of the body
that is subject to repeated pressure or irritation.
Calluses are usually more than an inch wide–larger
than corns. They generally don’t hurt unless pressure
is applied.
Types of corns
A hard corn is a compact lump with a thick core.
Hard corns usually form on the tops of the toes, on the
outside of the little toe, or on the sole of the foot.
A soft corn is a small, inflamed patch of skin with
a smooth center. Soft corns usually appear between
the toes.
A seed corn is the least common type of corn.
Occurring only on the heel or ball of the foot, a seed
corn consists of a circle of stiff skin surrounding a plug
of cholesterol.
Types of calluses
A plantar callus, a callus that occurs on the sole of
the foot, has a white center. Hereditary calluses
develop where there is no apparent friction, run in
families, and occur most often in children.

Causes and symptoms
Corns and calluses form to prevent injury to skin
that is repeatedly pinched, rubbed, or irritated. The
most common causes are:


shoes that are too tight or too loose, or have very
high heels



tight socks or stockings



deformed toes



walking down a long hill, or standing or walking on a
hard surface for a long time

Jobs or hobbies that cause steady or recurring
pressure on the same spot can also cause calluses.
Symptoms include hard growths on the skin in
response to direct pressure. Corns may be extremely
sore and surrounded by inflamed, swollen skin.
GALE ENCYCLOPEDIA OF MEDICINE

Corns on toes. (Custom Medical Stock Photo. Reproduced by
permission.)

Diagnosis
Corns can be recognized on sight. A family physician or podiatrist may scrape skin off what seems to
be a callus, but may actually be a wart. If the lesion is a
wart, it will bleed. A callus will not bleed, but will
reveal another layer of dead skin.

Treatment
Corns and calluses do not usually require medical
attention unless the person who has them has diabetes
mellitus, poor circulation, or other problems that
make self-care difficult.
Treatment should begin as soon as an abnormality appears. The first step is to identify and eliminate
the source of pressure. Placing moleskin pads over
corns can relieve pressure, and large wads of cotton,
lamb’s wool, or moleskin can cushion calluses.
Using hydrocortisone creams or soaking feet in a
solution of Epsom salts and very warm water for at
least five minutes a day before rubbing the area with a
pumice stone will remove part or all of some calluses.
Rubbing corns just makes them hurt more.
Applying petroleum jelly or lanolin-enriched
hand lotion helps keep skin soft, but corn-removing
ointments that contain acid can damage healthy skin.
They should never be used by pregnant women or by
people who are diabetic or who have poor circulation.
1011

Coronary artery bypass graft surgery

It is important to see a doctor if the skin of a corn
or callus is cut, because it may become infected. If a
corn discharges pus or clear fluid, it is infected. A
family physician, podiatrist, or orthopedist may:


remove (debride) affected layers of skin



prescribe oral antibiotics to eliminate infection



drain pus from infected corns



inject cortisone into the affected area to decrease
pain or inflammation



perform surgery to correct toe deformities or remove
bits of bone

KEY TERMS
Ayurveda—Ayurveda is a system of wholistic medicine from India that aims to bring the individual
into harmony with nature. It provides guidance
regarding food and lifestyle, so that healthy people
can stay healthy and people with health challenges
can improve their health.
Bursitis—Inflammation of a bursa, a fluid-filled
cavity or sac. In the body, bursae are located at
places where friction might otherwise develop.

Alternative treatment
Standing and walking correctly can sometimes
eliminate excess foot pressure. Several types of bodywork can help correct body imbalances. Bodywork is a
term used for any of a number of systems, including
Aston-Patterning, the Feldenkrais method, and rolfing,
that manipulate the body through massage, movement
education, or meditational techniques.
Aloe (Aloe barbadensis) cream is an effective skin
softener, and two or three daily applications of calendula (Calendula officinalis) salve can soften skin and
prevent inflammation. One teaspoon of lemon juice
mixed with one teaspoon of dried chamomile
(Martricaria recutita) tea and one crushed garlic
clove dissolves thickened skin.
An ayurvedic practitioner may recommend the
following treatment:


apply each day a paste made by combining one teaspoon of aloe vera gel with half that amount of turmeric (Circuma longa)



bandage overnight



soak in warm water for 10 minutes every morning



massage gently with mustard (Brassica cruciferae) oil

Prevention
Corns and calluses can usually be prevented by
avoiding friction-causing activities and wearing shoes
that fit properly, are activity-appropriate, and are kept
in good repair. Soles and heels that wear unevenly may
indicate a need for corrective footwear or special
insoles. Socks and stockings should not cramp the
toes. Gloves, kneepads, and other protective gear
should also be worn as needed.
Feet should be measured, while standing, whenever buying new shoes. It is best to shop for shoes late
in the day, when feet are likely to be swollen. It is also
important to buy shoes with toe-wiggling room and to
try new shoes on both feet.
Resources
ORGANIZATIONS

American Podiatric Medical Association. 9312 Old
Georgetown Road, Bethesda, MD 20814-1698. (301)
571-9200. <http://www.apma.org>.
OTHER

‘‘Foot Disorders.’’ Foot Talk Home Page. <http://
www.foottalk.com/corns.htm>.

Maureen Haggerty

Prognosis
Most corns and calluses disappear about three
weeks after the pressure that caused them is eliminated. They are apt to recur if the pressure returns.
Extreme pain can change the way a person stands
or walks. Such changes can, in turn, cause pain in the
ankle, back, hip, or knee.
Bursitis, a painful, inflamed fluid-filled sac, can
develop beneath a corn. An ulcer or broken area
within a corn can reach to the bone. Infection can
have serious consequences for people who have diabetes or poor circulation.
1012

artery bypass graft
I Coronary
surgery
Definition
Coronary artery bypass graft surgery is a surgical
procedure in which one or more blocked coronary
arteries are bypassed by a blood vessel graft to restore
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
Coronary artery bypass graft surgery (also called
coronary artery bypass surgery, CABG, and bypass
operation) is performed to restore blood flow to the
heart. This relieves chest pain and ischemia, improves
the patient’s quality of life, and in some cases, prolongs the patient’s life. The goals of the procedure are
to enable the patient to resume a normal lifestyle and
to lower the risk of a heart attack.
The decision to perform coronary artery bypass
graft surgery is a complex one, and there is some
disagreement among experts as to when it is indicated.
Many experts feel that it has been performed too frequently in the United States. According to the
American Heart Association, appropriate candidates
for coronary artery bypass graft surgery include
patients with blockages in at least three major coronary arteries, especially if the blockages are in arteries
that feed the heart’s left ventricle; patients with angina
so severe that even mild exertion causes chest pain;
and patients who cannot tolerate percutaneous transluminal coronary angioplasty and do not respond well
to drug therapy. Coronary artery bypass graft surgery
often is the treatment of choice for patients with severe
coronary artery disease (three or more diseased arteries
with impaired function in the left ventricle).

Precautions
Coronary artery bypass graft surgery ideally
should be postponed for three months after a heart
attack. Patients should be medically stable before the
surgery, if possible.

Description
Coronary artery bypass graft surgery builds a
detour around one or more blocked coronary arteries
with a graft from a healthy vein or artery. The graft
goes around the clogged artery (or arteries) to create
new pathways for oxygen-rich blood to flow to the
heart. In the fall of 2003, a cardiac surgeon in Brazil
reported success using a synthetic coronary artery
bypass graft called the CardioPass on both an adult
and pediatric patient. The company that makes the
graft, CardioTech, was one of only two companies at
the time in clinical trials on humans with synthetic
grafts. This could be important, as some patients do
not have a healthy graft to use in bypass surgery.
GALE ENCYCLOPEDIA OF MEDICINE

Coronary artery bypass graft surgery is major
surgery performed in a hospital. The length of the
procedure depends upon the number of arteries being
bypassed, but it generally takes from four to six hours–
sometimes longer. The average hospital stay is four to
seven days. Full recovery from coronary artery bypass
graft surgery takes three to four months. Within four
to six weeks, people with sedentary office jobs can
return to work; people with physical jobs must wait
longer and sometimes change careers.
Coronary artery bypass graft surgery is widely
performed in the United States. About 516,000 of
these procedures were performed in 2001. The number
performed has declined somewhat in the past five to
10 years due increased use of less invasive coronary
angioplasty and stent therapy procedures.
Procedure
The surgery team for coronary artery bypass
graft surgery includes the cardiovascular surgeon,
assisting surgeons, a cardiovascular anesthesiologist, a perfusion technologist (who operates the
heart-lung machine), and specially trained nurses.
After general anesthesia is administered, the surgeon
removes the veins or prepares the arteries for grafting. If the saphenous vein is to be used, a series of
incisions are made in the patient’s thigh or calf.
More commonly, a segment of the internal mammary artery will be used and the incisions are made
in the chest wall. The surgeon then makes an incision
from the patient’s neck to navel, saws through the
breastbone, and retracts the rib cage open to expose
the heart. The patient is connected to a heart-lung
machine, also called a cardiopulmonary bypass
pump, that cools the body to reduce the need for
oxygen and takes over for the heart and lungs during
the procedure. The heart is then stopped and a cold
solution of potassium-enriched normal saline is
injected into the aortic root and the coronary
arteries to lower the temperature of the heart,
which prevents damage to the tissue.
Next, a small opening is made just below the
blockage in the diseased coronary artery. Blood will
be redirected through this opening once the graft is
sewn in place. If a leg vein is used, one end is connected
to the coronary artery and the other to the aorta. If a
mammary artery is used, one end is connected to the
coronary artery while the other remains attached to
the aorta. The procedure is repeated on as many coronary arteries as necessary. Most patients who have
coronary artery bypass graft surgery have at least
three grafts done during the procedure.
1013

Coronary artery bypass graft surgery

normal blood flow to the heart. These grafts usually
come from the patient’s own arteries and veins located
in the leg, arm, or chest.

Coronary artery bypass graft surgery

Aorta

Mammary artery
(from chest)

Aorta

Saphenous vein
Blocked
coronary
Blocked
coronary

Coronary bypass using
the mammary artery

Coronary bypass using
the saphenous vein

Coronary artery bypass graft surgery builds a detour around one or more blocked coronary arteries with a graft from a healthy
vein or artery. The graft goes around the clogged artery (or arteries) to create new pathways for oxygen-rich blood to flow to the
heart. (Illustration by Electronic Illustrators Group.)

Electric shocks start the heart pumping again after
the grafts have been completed. The heart-lung
machine is turned off and the blood slowly returns to
normal body temperature. After implanting pacing
electrodes (if needed) and inserting a chest tube, the
surgeon closes the chest cavity.
Success rate of coronary artery bypass graft
surgery
About 90% of patients experience significant
improvements after coronary artery bypass graft
surgery. Patients experience full relief from chest
pain and resume their normal activities in about
70% of cases; the remaining 20% experience partial relief. In 5–10% of coronary artery bypass
graft surgeries, the bypass graft stops supplying
blood to the bypassed artery within one year.
Younger people who are healthy except for the
heart disease do well with bypass surgery.
Patients who have poorer results from coronary
artery bypass graft surgery include those over the
age of 70, those who have poor left ventricular
function, or are undergoing a repeat surgery or
other procedures concurrently, and those who continue smoking, do not treat high cholesterol or
1014

other coronary risk factors, or have another debilitating disease.
Long term, symptoms recur in only about 3–4%
of patients per year. Five years after coronary artery
bypass graft surgery, survival expectancy is 90%, at 10
years it is about 80%, at 15 years it is about 55%, and
at 20 years it is about 40%.
Angina recurs in about 40% of patients after
about 10 years. In most cases, it is less severe than
before the surgery and can be controlled by drug
therapy. In patients who have had vein grafts, 40%
of the grafts are severely obstructed 10 years after the
procedure. Repeat coronary artery bypass graft surgery may be necessary, and is usually less successful
than the first surgery.
Minimally invasive coronary artery bypass graft
surgery
There are two new types of minimally invasive
coronary artery bypass graft surgery: port-access coronary artery bypass (also called PACAB or PortCAB)
and minimally invasive coronary artery bypass (also
called MIDCAB). These procedures are minimally
invasive because they do not require the neck-to-navel
GALE ENCYCLOPEDIA OF MEDICINE

Port-access coronary artery bypass enables surgeons to perform bypasses through smaller incisions.
Using a video monitor to view the procedure, the surgeon passes instruments through ports in the patient’s
chest to perform the bypass. Mammary arteries or leg
veins are used for the grafts. Minimally invasive coronary artery bypass is performed on a beating heart and is
appropriate only for bypasses of one or two arteries.
Small ports are made in the patient’s chest, along with a
small incision directly over the coronary artery to be
bypassed. Generally, the surgeon uses a mammary
artery for the bypass.
Early data on outcomes for port-access coronary
artery bypass and minimally invasive coronary artery
bypass are favorable. Mortality rates with port-access
coronary artery bypass and minimally invasive coronary artery bypass are both less than 3%–about the
same as in standard coronary artery bypass graft surgery. One clinical trial indicated that survival at seven
years was the same in minimally invasive coronary
artery bypass and standard coronary artery bypass
graft surgery, but that another intervention was necessary five times more often with minimally invasive
coronary artery bypass than with standard coronary
artery bypass graft surgery. The American Heart
Association Council on Cardio-Thoracic and
Vascular Surgery feels that both procedures appear
promising but that further study is needed. More
data covering longer term outcomes are necessary in
order to fully assess these procedures.

Preparation
The patient is usually admitted to the hospital the
day before the coronary artery bypass graft surgery is
scheduled. Coronary angiography has been previously
performed to show the surgeon where the arteries are
blocked and where the grafts might best be positioned.
The patient is given a blood-thinning drug—usually
heparin—that helps to prevent blood clots. The evening before the surgery, the patient showers with antiseptic soap and is shaved from chin to toes. After
midnight, food and fluids are restricted. A sedative is
GALE ENCYCLOPEDIA OF MEDICINE

prescribed on the morning of surgery and sometimes
the night before. Heart monitoring begins.

Aftercare
The patient recovers in a surgical intensive care
unit for at least the first two days after the surgery.
He or she is connected to chest and breathing tubes, a
mechanical ventilator, a heart monitor and other
monitoring equipment, and a urinary catheter. The
breathing tube and ventilator usually are removed
within six hours of surgery, but the other tubes
remain in place as long as the patient is in the intensive care unit. Drugs are prescribed to control pain
and to prevent unwanted blood clotting. The patient
is closely monitored. Vital signs and other parameters, such as heart sounds and oxygen and carbon
dioxide levels in arterial blood, are checked frequently. The chest tube is checked to ensure that it
is draining properly. The patient is fed intravenously
for the first day or two. Daily doses of aspirin are
started within six to 24 hours after the procedure.
Chest physiotherapy is started after the ventilator
and breathing tube are removed. The therapy
includes coughing, turning frequently, and taking
deep breaths. Other exercises will be encouraged to
improve the patient’s circulation and prevent complications due to prolonged bed rest.
If there are no complications, the patient begins to
resume a normal routine around the second day. This
includes eating regular food, sitting up, and walking
around a little bit. Before being released from the
hospital, the patient usually spends a few days under
observation in a non-surgical unit. During this time,
counseling is usually provided on eating right and
starting a light exercise program to keep the heart
healthy. Patients should eat a lot of fruits, vegetables,
grains, and non-fat or low-fat dairy products, and
reduce fats to less than 30% of all calories. An exercise
program usually will be tailored for the patient, who
will be encouraged to participate in a cardiac rehabilitation program where exercise will be supervised by
professionals. Cardiac rehabilitation programs,
offered by hospitals and other organizations, also
may include classes on heart-healthy living.
Full recovery from coronary artery bypass graft
surgery takes three to four months and is a gradual
process. Upon release from the hospital, the patient
will feel weak because of the extended bed rest in the
hospital. Within a few weeks, the patient should begin
to feel stronger.
While the incision scar from coronary artery
bypass graft surgery heals, which takes one to two
1015

Coronary artery bypass graft surgery

incision, sawing through the breastbone, or opening the
rib cage to expose the heart. Both procedures enable
surgeons to work on the coronary arteries through
small chest holes called ports and other small incisions.
Port-access coronary artery bypass requires the use of a
heart-lung machine but minimally invasive coronary
artery bypass does not. Advantages of these procedures
over standard coronary artery bypass graft surgery
include a shorter hospital stay, a shorter recovery period, and lower costs.

Coronary artery disease

KEY TERMS
Aorta—The main artery that carries blood from the
heart to the rest of the body The aorta is the largest
artery in the body.
Graft—To implant living tissue surgically. In coronary artery bypass graft surgery, healthy veins or
arteries are grafted to coronary arteries.
Mammary artery—A chest wall artery that descends from the aorta and is commonly used for
bypass grafts.
Saphenous vein—A long vein in the thigh or calf
commonly used for bypass grafts.
Ventricles—The left and right ventricles are the
large chambers of the heart. The ventricles propel
blood to the lungs and the rest of the body.

months, it may be sore. The scar should not be
bumped, scratched, or otherwise disturbed. An exercise test often is conducted after the patient leaves the
hospital to determine how effective the surgery was
and to confirm that progressive exercise is safe.

‘‘Graft Functioning Well in Coronary Artery Bypass
Patient.’’ Cardiovascular Week September 15, 2003: 38.
‘‘Poverty Increases Risk of Complications and Death After
CABG.’’ Heart Disease Weekly September 7, 2003: 19.
Simonsen, Michael. ‘‘Changing Role for Cardiac Surgery as
Use of Stents Continues Growth.’’ Cardiovascular
Device Update March 2003: 1–7.
Smith, Laquita Bowen. ‘‘Not-So-Open Heart Surgery: New
Equipment Allows for a Three-Inch Incision.’’
Memphis Business Journal 18, no. 53 (May 12 1997): 49.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave, Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
Texas Heart Institute. Heart Information Service. P.O. Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto
Teresa G. Odle

I Coronary artery disease
Definition

Risks
Coronary artery bypass graft surgery is major surgery and patients may experience any of the complications associated with major surgery. The risk of death
during coronary artery bypass graft surgery is two to
three percent. Possible complications include graft closure and development of blockages in other arteries,
long-term development of atherosclerotic disease of
saphenous vein grafts, abnormal heart rhythms, high
or low blood pressure, blood clots that can lead to a
stroke or heart attack, infections, and depression.
There is a higher risk for complications in patients who
are heavy smokers, patients who have serious lung, kidney, or metabolic problems, or patients who have a
reduced supply of blood to the brain. A 2003 report
also described poverty as a risk factor for complications
and death following coronary artery bypass surgery. It is
likely that being poor is associated with a greater degree
of stress, social isolation, and inadequate access to quick
or preventive treatment.
Resources
PERIODICALS

‘‘CardioPass Synthetic Coronary Artery Bypass Graft
Implanted in Baby.’’ Medical Devices & Surgical
Technology Week September 7, 2003: 79.
1016

Coronary artery disease is a narrowing or blockage of the arteries and vessels that provide oxygen and
nutrients to the heart. It is caused by atherosclerosis,
an accumulation of fatty materials on the inner linings
of arteries. The resulting blockage restricts blood flow
to the heart. When the blood flow is completely cut
off, the result is a heart attack.

Description
Coronary artery disease, also called coronary heart
disease or heart disease, is the leading cause of death for
both men and women in the United States. According to
the American Heart Association, deaths from coronary
artery disease have declined some since about 1990, but
more than 40,000 people still died from the disease in
2000. About 13 million Americans have active symptoms of coronary artery disease.
Coronary artery disease occurs when the coronary
arteries become partially blocked or clogged. This
blockage limits the flow of blood from the coronary
arteries, which are the major arteries supplying oxygen-rich blood to the heart. The coronary arteries
expand when the heart is working harder and needs
more oxygen. Arteries expand, for example, when a
person is climbing stairs, exercising, or having sex. If
GALE ENCYCLOPEDIA OF MEDICINE

Healthy coronary arteries are clean, smooth, and
slick. The artery walls are flexible and can expand to
let more blood through when the heart needs to work
harder. The disease process in arteries is thought to
begin with an injury to the linings and walls of the
arteries. This injury makes them susceptible to atherosclerosis and blood clots (thrombosis).

of a heart attack. Older women are twice as likely as
older men to die within a few weeks of a heart attack.
Major risk factors that can be changed are:


Smoking–Smoking increases both the chance of
developing coronary artery disease and the chance
of dying from it. Smokers are two to four times more
likely than are non-smokers to die of sudden heart
attack. They are more than twice as likely as nonsmokers to have a heart attack. They also are more
likely to die within an hour of a heart attack. Second
hand smoke also may increase risk.



High cholesterol–Dietary sources of cholesterol are
meat, eggs, and other animal products. The body
also produces it. Age, sex, heredity, and diet affect
one’s blood cholesterol. Total blood cholesterol is
considered high at levels above 240 mg/dL and borderline at 200-239 mg/dL. High-risk levels of
low-density lipoprotein (LDL cholesterol) begin at
130-159 mg/dL, depending on other risk factors.
Risk of developing coronary artery disease increases
steadily as blood cholesterol levels increase above
160 mg/dL. When a person has other risk factors,
the risk multiplies.



High blood pressure–High blood pressure makes the
heart work harder and weakens it over time. It
increases the risk of heart attack, stroke, kidney failure, and congestive heart failure. A blood pressure of
140 over 90 or above is considered high. As the
numbers rise, high blood pressure goes from Stage
1 (mild) to Stage 4 (very severe). In combination with
obesity, smoking, high cholesterol, or diabetes, high
blood pressure raises the risk of heart attack or
stroke several times.



Lack of physical activity–Lack of exercise increases
the risk of coronary artery disease. Even modest
physical activity, like walking, is beneficial if done
regularly.



Diabetes mellitus–The risk of developing coronary
artery disease is seriously increased for diabetics.
More than 80% of diabetics die of some type of
heart or blood vessel disease.

Causes and symptoms
Coronary artery disease is usually caused by
atherosclerosis. Cholesterol and other fatty substances
accumulate on the inner wall of the arteries. They
attract fibrous tissue, blood components, and calcium,
and
harden
into
artery-clogging
plaques.
Atherosclerotic plaques often form blood clots that
also can block the coronary arteries (coronary thrombosis). Congenital defects and muscle spasms can also
block blood flow. Recent research indicates that infection from organisms such as chlamydia bacteria may
be responsible for some cases of coronary artery
disease.
A number of major contributing factors increase
the risk of developing coronary artery disease. Some
of these can be changed and some cannot. People with
more risk factors are more likely to develop coronary
artery disease.
Major risk factors
Major risk factors significantly increase the
chance of developing coronary artery disease. Those
that cannot be changed are:


Heredity–People whose parents have coronary
artery disease are more likely to develop it. African
Americans also are at increased risk because they
experience a higher rate of severe hypertension than
whites.



Sex–Men are more likely to have heart attacks than
women and to have them at a younger age. Over age
60, however, women have coronary artery disease at
a rate equal to that of men.



Age–Men who are 45 years of age and older and
women who are 55 years of age and older are more
likely to have coronary artery disease. Occasionally,
coronary disease may strike a person in the 30s.
Older people (those over 65) are more likely to die

GALE ENCYCLOPEDIA OF MEDICINE

Contributing risk factors
Contributing risk factors have been linked to coronary artery disease, but the degree of their significance is not known yet. Contributing risk factors are:


Hormone replacement therapy–Evidence from a
large trial called the Women’s Health Initiative
released in 2002 and 2003 found that hormone replacement therapy is a risk factor for coronary artery
disease in postmenopausal women. The therapy was
1017

Coronary artery disease

the arteries are unable to expand, the heart is deprived
of oxygen (myocardial ischemia). When the blockage
is limited, chest pain or pressure, called angina, may
occur. When the blockage cuts off the flow of blood,
the result is heart attack (myocardial infarction or
heart muscle death).

Coronary artery disease

once thought to help protect women against heart
disease, but in the trial, it was discovered that it was
harmful to women with existing coronary artery
disease.


Obesity–Excess weight increases the strain on the
heart and increases the risk of developing coronary
artery disease even if no other risk factors are present. Obesity increases blood pressure and blood
cholesterol and can lead to diabetes.



Stress and anger–Some scientists believe that stress
and anger can contribute to the development of coronary artery disease and increase the blood’s tendency to form clots (thrombosis). Stress, the mental
and physical reaction to life’s irritations and challenges, increases the heart rate and blood pressure
and can injure the lining of the arteries. Evidence
shows that anger increases the risk of dying from
heart disease. The risk of heart attack is more than
double after an episode of anger.

Chest pain (angina) is the main symptom of coronary heart disease but it is not always present. Other
symptoms include shortness of breath, and chest heaviness, tightness, pain, a burning sensation, squeezing,
or pressure either behind the breastbone or in the
arms, neck, or jaws. Many people have no symptoms
of coronary artery disease before having a heart
attack; 63% of women and 48% of men who died
suddenly of coronary artery disease had no previous
symptoms of the disease, according to the American
Heart Association.

Diagnosis
Diagnosis begins with a visit to the physician, who
will take a medical history, discuss symptoms, listen to
the heart, and perform basic screening tests. These
tests will measure weight, blood pressure, blood lipid
levels, and fasting blood glucose levels. Other diagnostic tests include resting and exercise electrocardiogram, echocardiography, radionuclide scans, and
coronary angiography. The treadmill exercise (stress)
test is an appropriate screening test for those with high
risk factors even when they feel well.
An electrocardiogram (ECG) shows the heart’s
activity and may reveal a lack of oxygen (ischemia).
Electrodes covered with conducting jelly are placed on
the patient’s chest, arms, and legs. They send impulses
of the heart’s activity through an oscilloscope (a monitor) to a recorder that traces them on paper. The test
takes about 10 minutes and is performed in a physician’s office. A definite diagnosis cannot be made from
electrocardiography. About 50% of patients with
1018

significant coronary artery disease have normal resting electrocardiograms. Another type of electrocardiogram, known as the exercise stress test, measures
how the heart and blood vessels respond to exertion
when the patient is exercising on a treadmill or a
stationary bike. This test is performed in a physician’s
office or an exercise laboratory. It takes 15–30 minutes. It is not perfectly accurate. It sometimes gives a
normal reading when the patient has a heart problem
or an abnormal reading when the patient does not.
If the electrocardiogram reveals a problem or is
inconclusive, the next step is exercise echocardiography
or nuclear scanning (angiography). Echocardiography,
cardiac ultrasound, uses sound waves to create an image
of the heart’s chambers and valves. A technologist applies
gel to a hand-held transducer, then presses it against the
patient’s chest. The heart’s sound waves are converted
into an image that can be displayed on a monitor. It does
not reveal the coronary arteries themselves, but can detect
abnormalities in heart wall motion caused by coronary
disease. Performed in a cardiology outpatient diagnostic
laboratory, the test takes 30–60 minutes.
Radionuclide angiography enables physicians to
see the blood flow of the coronary arteries. Nuclear
scans are performed by injecting a small amount of
radiopharmaceutical such as thallium into the bloodstream. A device that uses gamma rays to produce an
image of the radioactive material (gamma camera)
records pictures of the heart. Radionuclide scans are
not dangerous. The radiation exposure is about the
same as that in a chest x ray. The tiny amount of radioactive material used disappears from the body in a few
days. Radionuclide scans cost about four times as much
as exercise stress tests but provide more information.
In radionuclide angiography, a scanning camera
passes back and forth over the patient who lies on a
table. Radionuclide angiography is usually performed
in a hospital’s nuclear medicine department and takes
30–60 minutes. Thallium scanning usually is done in
conjunction with an exercise stress test. When the
stress test is finished, thallium or sestamibi is injected.
The patient resumes exercise for one minute to absorb
the thallium. For patients who cannot exercise, cardiac blood flow and heart rate may be increased by
intravenous dipyridamole (Persantine) or adenosine.
Thallium scanning is done twice, immediately after
injecting the radiopharmaceutical and again four
hours (and maybe 24 hours) later. It is usually performed in a hospital’s nuclear medicine department.
Each scan takes 30–60 minutes.
Coronary angiography is the most accurate
method for making a diagnosis of coronary artery
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Coronary artery disease can be treated many ways.
The choice of treatment depends on the severity of the
disease. Treatments include lifestyle changes and drug
therapy, percutaneous transluminal coronary angioplasty, and coronary artery bypass surgery. Coronary
artery disease is a chronic disease requiring lifelong
care. Angioplasty or bypass surgery is not a cure.
People with less severe coronary artery disease
may gain adequate control through lifestyle changes
and drug therapy. Many of the lifestyle changes that
prevent disease progression–a low-fat, low-cholesterol
diet, weight loss if needed, exercise, and not smoking–
also help prevent the disease from developing.
Drugs such as nitrates, beta-blockers, and
calcium-channel blockers relieve chest pain and complications of coronary artery disease, but they cannot
clear blocked arteries. Nitrates (nitroglycerin)
improve blood flow to the heart. Beta-blockers (acebutelol, propranolol) reduce the amount of oxygen
required by the heart during stress. One type of calcium-channel blocker (verapamil, diltiazem hydrochloride) helps keep the arteries open and reduces
blood pressure. Aspirin helps prevent blood clots
from forming on plaques, reducing the likelihood of
a heart attack. Cholesterol-lowering medications are
also indicated in most cases.
Percutaneous transluminal coronary angioplasty
and bypass surgery are procedures that enter the body
(invasive procedures) to improve blood flow in the
coronary arteries. Percutaneous transluminal coronary angioplasty, usually called coronary angioplasty,
is a non-surgical procedure. A catheter tipped with a
balloon is threaded from a blood vessel in the thigh
into the blocked artery. The balloon is inflated, compressing the plaque to enlarge the blood vessel and
open the blocked artery. The balloon is deflated, and
GALE ENCYCLOPEDIA OF MEDICINE

the catheter is removed. Coronary angioplasty is performed in a hospital and generally requires a stay of
one or two days. Coronary angioplasty is successful
about 90% of the time, but for one-third of patients,
the artery narrows again within six months. The procedure can be repeated. It is less invasive and less
expensive than coronary artery bypass surgery.
In coronary artery bypass surgery, a healthy
artery or vein from an arm, leg, or chest wall is used
to build a detour around the coronary artery blockage.
The healthy vessel then supplies oxygen-rich blood to
the heart. Bypass surgery is major surgery. It is appropriate for those patients with blockages in two or three
major coronary arteries, those with severely narrowed
left main coronary arteries, and those who have not
responded to other treatments. It is performed in
a hospital under general anesthesia. A heart-lung
machine is used to support the patient while the
healthy vein or artery is attached past the blockage
to the coronary artery. About 70% of patients who
have bypass surgery experience full relief from angina;
about 20% experience partial relief. Only about 3–4%
of patients per year experience a return of symptoms.
Survival rates after bypass surgery decrease over time.
At five years after surgery, survival expectancy is 90%;
at 10 years about 80%, at 15 years about 55%, and at
20 years about 40%.
Various semi-experimental surgical procedures
for unblocking coronary arteries are currently being
studied. Atherectomy is a procedure in which the surgeon shaves off and removes strips of plaque from the
blocked artery. In laser angioplasty, a catheter with a
laser tip is inserted into the affected artery to burn or
break down the plaque. A metal coil called a stent can
be implanted permanently to keep a blocked artery
open. Stenting is becoming more common.

Alternative treatment
Natural therapies may reduce the risk of certain
types of heart disease, but once symptoms appear,
conventional medical attention is necessary. A healthy
diet (including cold-water fish as a source of essential
fatty acids) and exercise, important components of
conventional prevention and treatment strategies,
also are emphasized in alternative approaches to coronary artery disease. Herbal medicine offers a variety
of remedies that may have a beneficial effect on coronary artery disease. For example, ginger (Zingiber
officinale) may help reduce cholesterol. Garlic
(Allium sativum), ginger, and hot red or chili peppers
all are circulatory enhancers that can help prevent
blood clots. Yoga and other bodywork, massage,
1019

Coronary artery disease

disease, but it also is the most invasive. It is a form of
cardiac catheterization that shows the heart’s chambers, great vessels, and coronary arteries using x-ray
technology. During coronary angiography the patient
is awake but sedated. ECG electrodes are placed on
the patient’s chest and an intravenous line is inserted.
A local anesthetic is injected into the site where the
catheter will be inserted. The cardiologist inserts a
catheter into a blood vessel and guides it into the
heart. A contrast dye is injected to make the heart
visible on x-ray cinematography. Coronary angiography is performed in a cardiac catheterization laboratory either in an outpatient or inpatient surgery unit. It
takes from 30 minutes to two hours.

Coronary artery disease

relaxation therapies, and talking therapies also may
help prevent coronary artery disease and stop, or even
reverse, the progression of atherosclerosis. Vitamin
and mineral therapy to reduce, reverse, or protect
against coronary artery disease include chromium;
calcium and magnesium; B-complex vitamins; the antioxidant vitamins C and E; selenium; and zinc.
Traditional Chinese medicine may recommend herbal
remedies, massage, acupuncture, and dietary modification. However, studies released in 2003 showed that
vitamins C and E fell short of claims that they helped
narrow blockage caused by coronary artery disease. In
fact, high doses of the vitamins should be avoided.

Prognosis
In many cases, coronary artery disease can be successfully treated. Advances in medicine and healthier
lifestyles have caused a substantial decline in death rates
from coronary artery disease since the mid-1980s. New
diagnostic techniques enable doctors to identify and
treat coronary artery disease in its earliest stages. New
technologies and surgical procedures have extended the
lives of many patients who would otherwise have died.
Research on coronary artery disease continues.

Prevention
A healthy lifestyle can help prevent coronary
artery disease and help keep it from progressing. A
heart-healthy lifestyle includes eating right, regular
exercise, maintaining a healthy weight, no smoking,
moderate drinking, no recreational drugs, controlling
hypertension, and managing stress. Cardiac rehabilitation programs are excellent to help prevent recurring
coronary problems for people who are at risk and who
have had coronary events and procedures.
Eating right
A healthy diet includes a variety of foods that are
low in fat, especially saturated fat, low in cholesterol,
and high in fiber. It includes plenty of fruits and vegetables, nuts and whole grains, and limited sodium.
Some foods are low in fat but high in cholesterol and
some are low in cholesterol but high in fat. Saturated
fat raises cholesterol and, in excessive amounts,
increases the amount of the clot-forming proteins in
blood. Polyunsaturated and monounsaturated fats are
good for the heart. Fat should comprise no more than
30% of total daily calories.
Cholesterol, a waxy substance containing fats, is
found in foods such as meat, eggs, and other animal
products. It also is produced in the liver. Soluble fiber
1020

can help lower cholesterol. Dietary cholesterol should
be limited to about 300 milligrams per day. Many
popular lipid-lowering drugs can reduce LDL cholesterol by an average of 25–30% when used with a lowfat, low-cholesterol diet.
Fruits and vegetables are rich in fiber, vitamins,
and minerals. They are low calorie and nearly fat free.
Vitamin C and beta-carotene, found in many fruits
and vegetables, keep LDL cholesterol from turning
into a form that damages coronary arteries.
Excess sodium can increase the risk of high blood
pressure. Many processed foods contain large
amounts of sodium. Daily intake should be limited
to about 2,400 milligrams, about the amount in a
teaspoon of salt.
The ‘‘Food Guide’’ Pyramid developed by the
U.S. Departments of Agriculture and Health and
Human Services provides easy-to-follow guidelines
for daily heart-healthy eating. It recommends 6 to 11
servings of bread, cereal, rice, and pasta; three to five
servings of vegetables; two to four servings of fruit;
two to three servings of milk, yogurt, and cheese; and
two to three servings of meat, poultry, fish, dry beans,
eggs, and nuts. Fats, oils, and sweets should be used
sparingly. Canola and olive oil are better for the heart
than other cooking oils. Coronary patients should
be on a strict diet. In 2003, the American Heart
Association advised a diet rish in fatty fish such as
salmon, herring, trout, or sardines. If people cannot
eat daily servings of these fish, the association recommends three fish oil capsules per day.
Regular exercise
Aerobic exercise can lower blood pressure, help
control weight, and increase HDL (‘‘good’’) cholesterol. It may keep the blood vessels more flexible. The
Centers for Disease Control and Prevention and the
American College of Sports Medicine recommend
moderate to intense aerobic exercise lasting about
30 minutes four or more times per week for maximum
heart health. Three 10-minute exercise periods also are
beneficial. Aerobic exercise–activities such as walking,
jogging, and cycling–uses the large muscle groups and
forces the body to use oxygen more efficiently. It also
can include everyday activities such as active gardening, climbing stairs, or brisk housework. People with
coronary artery disease or risk factors should consult a
doctor before beginning an exercise program.
Maintaining a desirable body weight
About one-fourth of all Americans are overweight
and nearly one-tenth are obese, according to the
GALE ENCYCLOPEDIA OF MEDICINE

Avoiding recreational drugs
Smoking has many adverse effects on the heart. It
increases the heart rate, constricts major arteries, and
can create irregular heartbeats. It raises blood pressure, contributes to the development of plaque,
increases the formation of blood clots, and causes
blood platelets to cluster and impede blood flow.
Heart damage caused by smoking can be repaired by
quitting. Even heavy smokers can return to heart
health. Several studies have shown that ex-smokers
face the same risk of heart disease as non-smokers
within five to 10 years after quitting.
Drink in moderation. Modest consumption of alcohol may actually protect against coronary artery disease
because alcohol appears to raise levels of HDL cholesterol. The American Heart Association defines moderate consumption as one ounce of alcohol per day,
roughly one cocktail, one 8-ounce glass of wine, or
two 12-ounce glasses of beer. However, even moderate
drinking can increase risk factors for heart disease for
some people (by raising blood pressure, for example).
Excessive drinking always is bad for the heart. It usually
raises blood pressure and can poison the heart and cause
abnormal heart rhythms or even heart failure.
Do not use other recreational drugs. Commonly
used recreational drugs, particularly cocaine and
‘‘crack,’’ can seriously harm the heart and should
never be used.
Seeking treatment for hypertension
High blood pressure, one of the most common and
serious risk factors for coronary artery disease, can be
controlled completely through lifestyle changes and medication. Moderate hypertension can be controlled by
reducing dietary intake of sodium and fat, exercising
regularly, managing stress, abstaining from smoking,
and drinking alcohol in moderation. People for whom
these changes do not work or people with severe hypertension may be helped by many categories of medication.
Managing stress
Everyone experiences stress. Stress sometimes
can be avoided and when it is inevitable, it can be
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Atherosclerosis—A process in which the walls of
the coronary arteries thicken due to the accumulation of plaque in the blood vessels. Atherosclerosis
is the cause of coronary artery disease.
Angina—Chest pain that happens when diseased
blood vessels restrict the flow of blood to the heart.
Angina often is the first symptom of coronary artery
disease.
Beta-blocker—A drug that blocks some of the
effects of fight-or-flight hormone adrenaline (epinephrine and norepinephrine), slowing the heart
rate and lowering the blood pressure.
Calcium-channel blocker—A drug that blocks the
entry of calcium into the muscle cells of small
blood vessels (arterioles) and keeps them from
narrowing.
Coronary arteries—The main arteries that provide
blood to the heart. The coronary arteries surround
the heart like a crown, coming out of the aorta,
arching down over the top of the heart, and dividing into two branches. These are the arteries in
which coronary artery disease occurs.
HDL cholesterol—High-density lipoprotein cholesterol is a component of cholesterol that helps
protect against heart disease. HDL is nicknamed
‘‘good’’ cholesterol
LDL cholesterol—Low-density lipoprotein cholesterol is the primary cholesterol molecule.
High levels of LDL increase the risk of coronary
heart disease. LDL is nicknamed ‘‘bad’’
cholesterol.
Plaque—A deposit of fatty and other substances
that accumulate in the lining of the artery wall.
Triglyceride—A fat that comes from food or is
made from other energy sources in the body.
Elevated triglyceride levels contribute to the development of atherosclerosis.

controlled. It is particularly important for those at
risk for heart disease. A 2003 report showed that
middle-aged men with high anxiety were less likely
to adhere to heart healthy lifestyle practices.
Techniques for controlling stress include: taking
life more slowly, spending more time with family
and friends, thinking positively, getting enough
sleep, exercising, and practicing relaxation
techniques.
1021

Coronary artery disease

Surgeon General’s Report on Nutrition and Health.
People who are 20% or more over their ideal body
weight have an increased risk of developing coronary
artery disease. Losing weight can help reduce total and
LDL cholesterol, reduce triglycerides, and boost HDL
cholesterol. It also may reduce blood pressure. Eating
right and exercising are two key components of losing
weight.

Coronary stenting

Purpose

Resources
BOOKS

Notelovitz, Morris, and Diana Tonnessen. The Essential
Heart Book for Women. New York: St. Martin’s Press,
1996.
Texas Heart Institute. ‘‘Coronary Artery Disease, Angina,
and Heart Attacks.’’ In Texas Heart Institute Heart
Owner’s Handbook. New York: JohnWiley & Sons,
1996.
PERIODICALS

‘‘For Fighting Heart Disease, Vitamins C and E Fall Short.’’
Tufts University Health and Nutrition Newsletter
January 2003: 2.
Jancin, Bruce. ‘‘High Anxiety Level Predicts Heartunhealthy Lifestyle.’’ Internal Medicine News March
15, 2003: 25.
‘‘Optimal Diets for Prevention of CHD.’’ Clinical
Cardiology Alert February 2003.
Wellbery, Caroline. ‘‘No HRT or Antioxidants in Women
with Coronary Disease.’’ American Family Physician
March 15, 2003: 1371.
Zoler, Michael L. ‘‘Heart Association Advocates Fish Oil
Supplements.’’ Family Practice News January 15,
2003: 6.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave, Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. P.O. Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto
Teresa G. Odle

Coronary disease see Coronary artery
disease
Coronary heart disease see Coronary artery
disease

I Coronary stenting
Definition
A coronary stent is an artificial support device
used in the coronary artery to keep the vessel open.
1022

The coronary stent is a relatively new tool used to
keep coronary arteries expanded, usually following a
balloon angioplasty. Balloon angioplasty is used in
patients with coronary artery disease. In this disease,
the blood vessels on the heart become narrow. When
this happens, the oxygen supply is reduced to the heart
muscle. The primary cause of coronary artery disease is
fat deposits blocking the arteries (atherosclerosis). In
many cases, balloon angioplasty is unsuccessful and
the vessel closes after the procedure (restenosis). By
forming a rigid support, the stent can prevent restenosis
and reduce the need for coronary bypass surgery. The
stent is usually a stainless steel mesh tube. Since the
stent will be placed inside an artery, the device comes
in various sizes to match the size of the artery.

Precautions
Any foreign object in the body, like a stent, will
increase the risk of thrombosis. Anticlotting medication is given to prevent this complication.

Description
Coronary stenting usually follows balloon angioplasty, which requires inserting a balloon catheter into
the femoral artery in the upper thigh. When this catheter is positioned at the location of the blockage in the
coronary artery, it is slowly inflated to widen that
artery, and is then removed. The stent catheter is
then threaded into the artery and the stent is placed
around a deflated balloon. When this is correctly positioned in the coronary artery, the balloon is inflated,
expanding the stent against the walls of the coronary
artery. The balloon catheter is removed, leaving the
stent in place to hold the coronary artery open. A
cardiac angiography will follow to insure that the
stent is keeping the artery open.

Alternative procedures
Balloon angioplasty and coronary stenting are
performed to relieve the symptoms of coronary artery
disease. By the time coronary artery disease progresses
and requires balloon angioplasty, there is no alternative to balloon angioplasty other than coronary
bypass surgery. Coronary bypass surgery carries
greater risks. However, since coronary artery disease
can be related to high fat diets, smoking, and lack of
exercise, changes in lifestyle may reduce the risk of
developing the disease. Various medications for cholesterol, high blood pressure, and diabetes also can
help treat or prevent coronary artery disease.
GALE ENCYCLOPEDIA OF MEDICINE

Balloon angioplasty—The use of a balloon
attached to a catheter to widen an artery that has
become narrowed. As the balloon is inflated, it
opens the artery.
Cardiac angiography—A procedure used to visualize blood vessels of the heart. A catheter is used to
inject a dye into the vessels; the vessels can then be
seen by x ray.
Catheter—A long thin flexible tube that can be
inserted into the body; in this case, it is threaded
to the heart.
Restenosis—The narrowing of a blood vessel after
it has been opened, usually by balloon angioplasty.
Thrombosis—The development of a blood clot in
the vessels. This thrombosis may clog a blood vessel and stop the flow of blood.

Preparation
Before the stent is inserted, the patient will probably be instructed to take aspirin for several days.
Aspirin can help decrease the possibility of blood
clots forming at the stent. Because anesthesia will be
used during the procedure, the patient should not eat
or drink after midnight of the previous day.

Aftercare
Following the procedure, blood thinners (anticoagulants) will be given through a needle in a vein
for about 24 hours. The patient should remain flat and
still for awhile to allow the femoral artery to heal from
the insertion of the catheter. Medication to control
blood clotting should be taken after the patient is
discharged from the hospital. A special diet may also
be recommended that is low in vitamin K and cholesterol. With time, the patient should begin light exercise, like walking. It is important that no magnetic
resonance imaging (MRI) tests are given for six months
because the magnetic field may move the stent.

Risks
Although coronary stents greatly reduce the risk
of restenosis following balloon angioplasty, there is
still some risk that the stented artery may close.
Thrombosis, bleeding, and artery damage are also
risks.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave, Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
OTHER

AdvocateHealthCare. <http://www.advocatehealth.com>.

Cindy L. A. Jones, PhD

Coronary thrombosis see Heart attack
Coronavirus infection see Common cold

I Corticosteroids
Definition
Corticosteroids are group of natural and synthetic
analogues of the hormones secreted by the hypothalamic-anterior pituitary-adrenocortical (HPA) axis,
more commonly referred to as the pituitary gland.
These include glucocorticoids, which are anti-inflammatory agents with a large number of other functions;
mineralocorticoids, which control salt and water balance primarily through action on the kidneys; and
corticotropins, which control secretion of hormones
by the pituitary gland.

Purpose
Glucocorticoids have multiple effects, and are
used for a large number of conditions. They affect
glucose utilization, fat metabolism, and bone development, and are potent anti-inflammatory agents. They
may be used for replacement of natural hormones in
patients with pituitary deficiency (Addison’s disease),
as well as for a wide number of other conditions
including, but not limited to, arthritis, asthma, anemia, various cancers, and skin inflammations.
Additional uses include inhibition of nausea and vomiting after chemotherapy, treatment of septic shock,
treatment of spinal cord injuries, and treatment of
hirisutism (excessive hair growth). The choice of drug
will vary with the condition. Cortisone and hydrocortisone, which have both glucocorticoid and mineralocorticoid effects, are the drugs of choice for
replacement therapy of natural hormone deficiency.
Synthetic compounds, which have greater anti-inflammatory effects and less effect on salt and water balance, are usually preferred for other purposes. These
compounds include dexamethasone, which is almost
1023

Corticosteroids

Resources

KEY TERMS

Corticosteroids

exclusively glucocorticoid in its actions, as well as
prednisone, prednisolone, betamethasone, trimacinolone, and others. Glucocorticoids are formulated in
oral dosage forms, topical creams and ointments, oral
and nasal inhalations, rectal foams, and ear and eye
drops.
Mineralocorticoids control the retention of
sodium in the kidneys. In mineralocorticoid deficiency, there is excessive loss of sodium through the
kidneys, with resulting water loss. Fludrocortisone
(Florinef) is the only drug available for treatment of
mineralocorticoid deficiency, and is available only in
an oral dosage form.
Corticotropin (ACTH, adrenocorticotropic hormone) stimulates the pituitary gland to release cortisone. A deficiency of corticotropic hormone will have
the same effects as a deficiency of cortisone. The hormone, which is available under the brand names
Acthar and Actrel, is used for diagnostic testing, to
determine the cause of a glucocorticoid deficiency, but
is rarely used for replacement therapy since direct
administration of glucocorticoids may be easier and
offers better control over dosages.

Recommended dosage
The dosage of glucocorticoids varies with the
drug, route of administration, condition being treated,
and patient. Consult specific references.
Fludrocortisone, for use in replacement therapy,
is normally dosed at 0.1 mg/day. Some patients
require higher doses. It should normally be administered in conjunction with cortisone or hydrocortisone.
ACTH, when used for diagnostic purposes, is
given as 10 to 25 units dissolved in 500 ml of 5%
dextrose injection infused IV over eight hours. A
long-acting form, which may be used for replacement
therapy, is given by subcutaneous (SC) or intramuscular (IM) injection at a dose of 40 to 80 units every
24–72 hours.

Precautions
Glucocorticoids
The most significant risk associated with administration of glucocorticoids is suppression of natural
corticosteroid secretion. When the hormones are
administered, they suppress the secretion of ACTH,
which in turn reduces the secretion of the natural
hormones. The extent of suppression varies with
dose, drug potency, duration of treatment, and individual patient response. While suppression is seen
1024

primarily with drugs administered systemically, it can
also occur with topical drugs such as creams and ointments, or drugs administered by inhalation. Abrupt
cessation of corticosteroids may result in acute adrenal
crisis (Addisonian crisis) that is marked by dehydration with severe vomiting and diarrhea, hypotension,
and loss of consciousness. Acute adrenal crisis is
potentially fatal.
Chronic overdose of glucocorticoids leads to
Cushingoid syndrome, which is clinically identical to
Cushing’s syndrome and differs only in that in
Cushingoid the excessive steroids are from drug
therapy rather than excessive glandular secretion.
Symptoms vary, but most people have upper body
obesity, rounded face, increased fat around the neck,
and thinning arms and legs. In its later stages, this
condition leads to weakening of bones and muscles
with rib and spinal column fractures.
The short term adverse effects of corticosteroids
are generally mild, and include indigestion, increased
appetite, insomnia, and nervousness. There are also a
very large number of infrequent adverse reactions, the
most significant of which is drug-induced paranoia.
Delirium, depression, menstrual irregularity, and
increased hair growth are also possible. Consult
detailed reviews for further information.
Long-term use of topical glucocorticoids can
result in thinning of the skin. Oral steroid inhalations
may cause fungal overgrowth in the oral cavity.
Patients must be instructed to rinse their mouths carefully after each dose. Corticosteroids are pregnancy
category C. The drugs have caused congenital malformations in animal studies, including cleft palate.
Breastfeeding should be avoided.
Mineralocorticoids
Because fludrocortisone has glucocorticoid activity as well as mineralocorticoid action, the same
hazards and precautions apply to fludrocortisone as
to the glucocorticoids. Overdose of fludrocortisone
may also cause edema, hypertension and congestive
heart failure.
Corticotropin has all the same risks as the glucocorticoids. Prolonged use may cause reduced response
to the stimulatory effects of corticotropin.
Warnings and contraindications
Use corticosteroids with caution in patients with
the following conditions:


osteoporosis or any other bone disease



current or past tuberculosis
GALE ENCYCLOPEDIA OF MEDICINE

Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.
Hormone—A substance that is produced in one
part of the body, then travels through the bloodstream to another part of the body where it has its
effect.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Ointment—A thick, spreadable substance that
contains medicine and is meant to be used on the
outside of the body.
Pregnancy category— A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: controlled human studies
have demonstrated no fetal risk. Category B: animal
studies indicate no fetal risk, but no human studies;
or adverse effects in animals, but not in well-controlled human studies. Category C: no adequate
human or animal studies; or adverse fetal effects
in animal studies, but no available human data.
Category D: evidence of fetal risk, but benefits outweigh risks. Category X: evidence of fetal risk. Risks
outweigh any benefits.



glaucoma or cataracts



infections of any type (virus, bacteria, fungus,
amoeba)



sores in the nose or recent nose surgery (if using nasal
spray forms of corticosteroids)



underactive or overactive thyroid



liver disease



stomach or intestine problems



diabetes



heart disease



high blood pressure



high cholesterol



kidney disease or kidney stones



myasthenia gravis



systemic lupus erythematosus (SLE)



emotional problems

GALE ENCYCLOPEDIA OF MEDICINE

skin conditions that cause the skin to be thinner and
bruise more easily
Interactions

Corticosteroids have many drug interactions.
Consult specific references.
Resources
ORGANIZATIONS

American Academy of Allergy, Asthma and Immunology.
611 East Wells Street, Milwaukee, WI 53202. (414) 2726071. <http://www.aaaai.org>.
Asthma and Allergy Foundation of America. 1125 15th
Street NW, Suite 502, Washington, DC 20005. (800)
727-8462. <http://www.aafa.org>.
National Heart, Lung and Blood Institute. National
Institutes of Health, P.O. Box 30105, Bethesda, MD
20824-0105. (301) 251-1222. <http://www.nhlbi.nih.
gov/nhlbi/nhlbi.htm>.

Samuel D. Uretsky, PharmD

I Corticosteroids, dermatologic
Definition
Dermatologic corticosteroids are anti-inflammatory
compounds formulated for application to the skin. They
are intended for local effects only and are not meant for
internal use.

Purpose
Dermatologic corticosteroids are used to treat
skin conditions that involve inflammation, usually
marked by redness or itching. These include contact
dermatitis, atopic dermatitis, nummular eczema, stasis
eczema, asteatotic eczema, lichen planus, lichen simplex chronicus, insect and arthropod bite reactions,
and first- and second-degree localized burns and
sunburns.
In addition, dermatologic corticosteroids may be
used together with other drugs to treat the symptoms
of other conditions which are marked by inflammation of the skin.

Description
All dermatologic steroids are based on the natural
hormone hydrocortisone, but most have been subject
to chemical modification to increase their
1025

Corticosteroids, dermatologic



KEY TERMS

Corticosteroids, dermatologic

effectiveness. While many chemical changes to the
original molecule will increase the anti-inflammatory
effects, the best known is halogenation, replacing one
or more of the carbon atoms in the molecule with an
atom of fluorine or, less often, chlorine. This change
increases the anti-inflammatory effects of the steroid
but also increases the risk of some adverse effects.
Topical steroids are usually classed by their
potency, ranging from very high to low potency. The
most powerful steroids include clobetasol propionate,
diflorasone diacetate, and halobetasol propionate.
The high and medium potency group includes betamethasone valerate, desoximetasone, fluocininide,
halcinonide, and fluandrenolide. Low potency topical
steroids include desonide, dexamethasone, fluocinolone acetate, and hydrocortisone.
Topical steroids are particularly affected by their
vehicle, which can alter the potency of the product and
is particularly important in view of the parts of the
body being treated. Lotions are liquid at room temperature and are usually the best choice for application to hairy areas of the body since they can easily
reach past the hair. Creams are semi-solid and appropriate for application to most areas. They are usually
designed to disappear and leave no sticky residue. This
feature makes them appropriate for areas such as the
palms of the hands, the face, or areas that are in direct
contact with clothing. Ointments are thicker than
creams and tend to stay on the skin longer than
creams. Pastes are particularly thick ointments, often
containing a powder such as zinc oxide, and may be
used where a protective effect is needed.
Because of variations in skin thickness, it is essential to match the potency of the steroid with the area
being treated. Areas of thick skin may require a very
potent steroid in order to penetrate the outer layer of
skin. In areas where the skin is thin, a high potency
steroid may increase the risk of serious adverse
reactions.

Recommended dosage
Most topical steroids are applied twice a day, but
applications as frequently as four times a day may be
appropriate. In some cases, penetration through the
skin may be increased by use of occlusion.

Precautions
Excessive use of topical corticosteroids may lead
to systemic side effects. Patients using high potency
steroids over large areas of the body for a prolonged
period should have adrenal function tests.
1026

Normally, areas covered by steroid creams should
not be bandaged, since doing so increases the absorption
of the steroid and may lead to increased adverse effects.
Some commercially available formulations of
topical corticosteroids contain sulfites that may
cause allergic reactions. Allergic reactions to other
ingredients in topical formulations are very infrequent
but have been reported.
Topical corticosteroids should not be used in
patients with markedly impaired circulation since
skin ulceration has occurred in these patients following use of the drugs.
Topical corticosteroids should be used with
extreme caution in areas where the skin is infected
and should never be used in infected areas unless the
infection is being appropriately treated.
When used properly, these medicines have not
been shown to cause problems in humans. As of
2005, studies on birth defects have not been done in
humans. However, studies in animals have shown that
topical corticosteroids, when applied to the skin in
large amounts or used for a long time, can cause
birth defects. Maternal use of topical corticosteroids
has not been reported to cause problems in nursing
babies when used properly. However, corticosteroids
should not be applied to the breasts before nursing.

Side effects
When dermatologic corticosteroids are used properly, adverse effects are very rare. Even so, the following effects have been reported:


blood-containing blisters on skin



burning and itching of skin



increased skin sensitivity (for some brands of betamethasone lotion)



lack of healing of skin condition



numbness in fingers



painful, red, or itchy, pus-containing blisters in hair
follicles



raised, dark red, wart-like spots on skin, especially
when used on the face



skin infection



thinning of skin with easy bruising

Excessive use, either because of use of an inappropriately potent steroid, prolonged use, or inappropriate use of occlusion has been known to lead to more
severe adverse effects. However, these reactions are
very rare.
GALE ENCYCLOPEDIA OF MEDICINE

Corticosteroids—Any of the steroid hormones produced by the adrenal cortex or their synthetic
equivalents.
Dermatitis—A disease in which the skin is red and
painful. This condition may have different causes.
In contact dermatitis, the redness is a reaction to
something touching the skin, such as a fabric dye or
a metal. Atopic dermatitis is an intense reddening
reaction, associated with allergies.
Eczema—A skin disease that causes redness, itching, and scaly or crusty sores. In asteatotic eczema
the skin is dry and scaly. Stasis eczema is caused by
reduced blood flow.
Lichen planus—An uncommon disorder involving
a recurrent, itchy, inflammatory rash or lesion on
the skin or in the mouth. The exact cause is
unknown, but the disorder is likely to be related to
an allergic or immune reaction. The skin lesions are
distinct from other disorders.
Systemic—Affecting the entire body.
Topical—Pertaining to a particular surface area and
affecting only the area to which it is applied.
Ulceration—Being eroded away, as by an ulcer.

Interactions
When used properly, topical steroids have no drug
interactions or interactions with foods because they do
not reach significant levels in the body. Application of
another ointment to the same area at the same time
may dilute the corticosteroid ointment and result in
lowered effectiveness.
Resources
BOOKS

Beers, Mark H., ed. Merck Manual of Medical
Information: Home Edition. Riverside, NJ: Simon &
Schuster, 2004.
Green, Steven M. Tarascon Pocket Pharmacopoeia. Delux
Labcoat Pocket Edition. Lompoc, CA: Tarascon
Publishing, 2005.
Physicians’ Desk Reference 2005. Montvale, NJ: Thomson
Healthcare, 2004.
White, Gary M., and Neil H. Cox. Diseases of the Skin: A
Color Atlas and Text. Orlando, FL: Mosby, 2002.

Samuel D. Uretsky, Pharm.D.
GALE ENCYCLOPEDIA OF MEDICINE

I Corticosteroids, inhaled
Definition
Inhaled corticosteroids are glucocorticoids (a class
of steroid hormones that are synthesized by the adrenal cortex and have anti-inflammatory activity) formulated to be used in the respiratory tract and lungs.

Purpose
Inhaled corticosteroids are glucocorticoid compounds designed to be applied directly to the tissues
of the respiratory tract. There are two types. The
intranasal are deposited into the nasal passages and
may be used to treat nasal polyps, perennial allergic
rhinitis, seasonal allergic rhinitis, and recurrent
chronic sinusitis.
The second type is used when the steroids are
designed for deposition further into the respiratory
tract. These are used for treatment of chronic asthma
and prevention of asthmatic attacks.
Because they have anti-inflammatory effects,
corticosteroids are invaluable in treatment of asthma
and other respiratory conditions which are associated with an allergic reaction. In many cases, the
corticosteroids are life saving. But systemic corticosteroids affect all parts of the body and may cause very
severe adverse effects, particularly with long-term
use. These reactions include inhibitions of the adrenal glands and weakening of bones. By administering
these drugs by inhalation, it is possible to target the
areas that require treatment and reduce the amount
of drug that reaches other parts of the body. Some
patients may be able to do without systemic steroids
entirely, while others can reduce their doses of systemic steroids and thereby reduce the risk and severity of unwanted effects.
The drugs used as inhaled steroids are all antiinflammatory corticosteroids and are very similar to
each other in action and use. The way they are formulated, the size of the particles, the design of the
inhaler, and whether the drugs are inhaled by the
mouth or nose determine how far into the respiratory tract the steroids go. The formulations designed
for nasal inhalation are only effective for nasal
polyps or rhinitis because the steroid does not penetrate deeply into the respiratory tract. Oral inhalations, containing the same drug but in different
particle size and inhaler design, deposit medication
deeply into the lungs and are of value in treatment of
asthma.
1027

Corticosteroids, inhaled

KEY TERMS

Corticosteroids, inhaled

Description
As of 2005, there are five corticosteroids designed
for inhalation:


beclomethasone dipropionate (Qvar)



budesonide (Pulmicort)



flunisolide (AeroBID)



fluticasone propionate (Flovent)



triamcinolone acetonide (Azmacort)

Although the different products vary in potency
and duration of action, once dose size and frequency
have been adjusted to offer comparable results, there
do not appear to be significant differences between the
drugs. The design of the inhalers, their ease of use, and
the training each patient receives in the proper use of
the inhaler may be of greater significance than the
drug itself.

Recommended dosage
Although the different products vary in milligram
potency, for practical purposes, doses are measured in
puffs on the inhaler. For example, beclomethasone
will deliver 40 micrograms each time the inhaler is
used, while triamcinolone delivers 100 micrograms
with each inhalation. However, the effects are essentially equal.
The appropriate dose of inhaled corticosteroids
depends on the severity of the case, and in some
instances, on what treatment has been used prior to
starting inhaled steroid therapy. The doses listed are
typical of the inhaled steroids used for asthma therapy
but do not represent all possible cases:


beclomethasone: one to two puffs two times a day



budesonide: one to two puffs two times a day



flunisolide: two puffs two times a day



fluticasone propionate: available in forms that deliver either 50 or 100 micrograms of fluticase in each
puff; typical initial dose, 100 micrograms two times a
day, representing either one puff of the 100 microgram product or two puffs of the 50 microgram
product



triamcinolone acetonide: two puffs three or four
times a day or four puffs twice a day, not to exceed
16 puffs daily

Precautions
Particular care is essential for patients who are
transferred from systemic corticosteroids to inhaled
1028

steroids. Because the long-term use of oral steroids
lowers the output of these compounds from the adrenal gland and normal production does not recur for
several months, patients who have their oral doses
reduced are at risk of adrenal insufficiency. This condition may become particularly serious in the event of
trauma, surgery, or infections. While inhaled steroids
may provide adequate control of asthma during these
periods, the inhaled drugs do not replace the systemic
compounds. In the event of stress or a severe asthma
attack, oral therapy must immediately begin. Regular
testing for cortisol levels is essential until the normal
levels have been resumed.
For patients who had been on systemic therapy and
are being switched to corticosteroid inhalation, the
immediate period during which the oral dose is reduced
may cause symptoms, including joint or muscle pain,
tiredness, and depression. Continuous monitoring is
required until normal functions have been resumed.
It is essential that patients learn proper use of
inhalers. If inhalers are not used properly, the corticosteroids may not reach their intended site of action.
Instead, they may be left in the mouth or swallowed
and be deposited in the digestive tract. This situation
may increase the risk of adverse effects, while reducing
the protection from asthmatic attacks.
Inhaled corticosteroids are not for treatment of
acute asthmatic attacks or rapid relief of bronchospasm.
Inhaled corticosteroids are designated as pregnancy category C. This designation means one of two
levels of knowledge concerning the drugs adverse
effects. In one instance, studies on animals show
adverse fetal effects but there are no controlled studies
on women. In the other instance, no studies on animals and women are not available.

Side effects
It can be difficult to evaluate the side effects of
inhaled corticosteroids because many of the reported
adverse effects are closely associated with dose reduction
or discontinuation of systemic steroids. Not all of the
adverse reactions listed have been associated with all of
the marketed inhaled steroids, but because of the similarities between these drugs, an adverse reaction reported
with one must be considered possible for the others.
The most common severe problem is white
patches in the mouth due to localized infection.
Additional common side effects are:


cough



general aches and pains or general feeling of illness
GALE ENCYCLOPEDIA OF MEDICINE

muscle wasting



numbness and weakness of hands and feet

Adrenal glands—The two glands that are located
on top of the kidneys. These glands secrete several
hormones, including the glucocorticoids which,
among other things, influence the way the immune
system works, and the mineralocorticoids, which
affect retention of water and sodium.



weakness



swelling of face, lips, or eyelids



tightness in chest, troubled breathing, or wheezing

Glucocorticoid—A class of steroid hormones that
are synthesized by the adrenal cortex and have
anti-inflammatory activity.
Perennial—Present at all seasons of the year.

Because inhaled steroids do not reach therapeutic
levels in the blood stream, there are no serious interactions. Ketoconazole (Nizoral), an antifungal agent,
has been reported to increase blood levels of budesonide and fluticasone, but it is unclear whether this has
any importance when the steroids are administered by
inhalation.

Polyp—A small vascular growth on the surface of a
mucous membrane.
Respiratory tract— The air passages from the nose
to the air sacs of the lungs, including the pharynx,
larynx, trachea, and bronchi.
Rhinitis—Inflammation of the mucous membranes
of the nose.



greenish-yellow mucus in nose



headache



hoarseness or other voice changes



loss of appetite



runny, sore, or stuffy nose



unusual tiredness



weakness

Very rare but severe adverse effects include the
following:


blindness, blurred vision, eye pain



large hives



bone fractures



diabetes mellitus (increased hunger, thirst, or
urination)



excess facial hair in women



fullness or roundness of face, neck, and trunk



growth reduction in children or adolescents



heart problems



high blood pressure



hives and skin rash



impotence in males



lack of menstrual periods

GALE ENCYCLOPEDIA OF MEDICINE

Interactions

Resources
BOOKS

Austen, K. Frank, ed. Samter’s Immunological Diseases.
Baltimore, MD: Lippincott Williams & Wilkens, 2001.
Beers, Mark H., ed. Merck Manual of Medical Information:
Home Edition. Riverside, NJ: Simon & Schuster, 2004.
Physicians’ Desk Reference 2005. Montvale, NJ: Thomson
Healthcare, 2004.

Samuel D. Uretsky, Pharm.D.

I Corticosteroids, systemic
Definition
Corticosteroids are a group of drugs which are
chemically related to the hormones produced by the
adrenal glands as a response to adrenocorticotropic
hormone (ACTH), but excluding the sex hormones
that are produced by this gland. The primary adrenal
corticosteroids are cortisol and aldosterone. Cortisol
is a glucocorticoid, responsible for influencing carbohydrate, fat, and protein metabolism. Aldosterone is a
mineralocorticoid, responsible for regulating salt and
water balance.
All corticosteroids, both natural ones and those
which have been developed synthetically, share a similar chemical structure, which is based on the structure
of cholesterol.

Purpose
The primary purpose of corticosteroids is replacement of naturally occurring hormones when the
1029

Corticosteroids, systemic



KEY TERMS

Corticosteroids, systemic

adrenal glands do not make enough of the natural
hormones. Known as Addison’s disease, this deficit is
marked by low blood pressure, weight loss, loss of
appetite, weakness, and a bronze-like hyperpigmentation of the skin. Addison’s disease requires both glucocorticoid and mineralocorticoid treatment.
Because the glucocorticoids inhibit some portions
of the immune response, they are used in treatment
of a large number of diseases. The following list
includes some of the established uses of systemic
corticosteroids.


acute, severe allergic reactions



arthritis, osteoarthritis, rheumatoid arthritis, psoriatic
arthritis, and gouty arthritis



adrenocortical insufficiency



allergic conjunctivitis



allergic rhinitis



anemia



(acquired hemolytic and congenital hypoplastic)



ankylosing spondylitis



asthma



beryliosis



bursitis



corneal ulcers



Crohn’s disease



dermatitis (atopic,
seborrheic)



dermatomyositis



erythema multiforme



erythroblastopenia



herpes zoster of the eye



hypercalcemia secondary to cancer



hypersensitivity reactions



idiopathic thrombocytopenic purpura



leukemia



lupus erythematosis



lymphoma



multiple myeloma



multiple sclerosis, acute exacerbations



mycosis fungoides



optic neuritis



pemphigus



pneumonitis (aspiration)

1030



rheumatic carditis



Stevens-Johnson syndrome



thrombocytopenia



trichinosis with nerve or heart involvement



tuberculosis, disseminated and fulminating



tuberculous meningitis



ulcerative colitis

Dexamethasone, a related corticosteroid, is
widely used to prevent the nausea and vomiting associated with cancer therapy.
Glucocorticoid treatment is not a cure for any
disease or condition, but it may be used as supportive
therapy in addition to other treatments.

Description

contact,

exfoliative,

Because they both have mineralocorticoid and
glucocorticoid effects, cortisone and hydrocortisone
are preferred for use in treating adrenal insufficiency.
When glucocorticoids are used for their antiinflammatory and immunosuppressant properties
and their effects on blood and lymphatic systems,
synthetic compounds, which have increased glucocorticoid effects and minimal mineralocorticoid effects,
are generally preferred.

and

A number of systemic corticosteroid compounds
are commercially available. Although they are generally similar, they vary in their potency, sodiumretaining effects, and duration of action.
Short acting
Cortisone has both glucocorticoid and mineralocorticoid effects. It has the lowest potency of the commercially available corticosteroids and a short
duration of action. It is appropriate for replacement
therapy in patients with adrenal insufficiency.
Hydrocortisone has both glucocorticoid and
mineralocorticoid effects. It is more potent than cortisone and has a somewhat longer duration of action.
Although hydrocortisone may be used for its systemic
effects, it is most commonly used in skin preparations.
Intermediate acting
Prednisone is probably the most widely used of
the systemic steroids. It has about half the sodiumretaining effects of hydrocortisone but several times
the anti-inflammatory effects. Because of the low level
of mineralocorticoid effects, however, prednisone is
not suitable for treatment of adrenal insufficiency
GALE ENCYCLOPEDIA OF MEDICINE

Triamcinolone is slightly more potent than prednisone or prednisolone but has no sodium-retaining
effects. It is administered various ways, including
inhalation for respiratory problems and as ointments
and creams for skin conditions. Methylprednisolone,
which is similar to triamcinolone, is most commonly
given by injection.
Long acting
Dexamethasone is a very potent glucocorticoid,
with no mineralocorticoid activity. It is used in various
forms, including tablets, injection, ointments, and eye
and eardrops. In cancer treatment, dexamethasone is
used both for its corticosteroid properties and as an
antinauseant, to help control the side effects of other
drugs. Betamethasone is similar to dexamethasone.
Although the drug is available for systemic use, it is
more commonly used in the form of inhalations and
ointments. Other corticosteroids are available but are
most often used in inhalation form, for asthma, allergic rhinitis, or other respiratory conditions.

Recommended dosage
Dosages of corticosteroids must be individualized
based on the drug selected, the condition being treated, and the response of the patient. In adrenal insufficiency, a dose equivalent to 25 mg of cortisone or
20 mg of hydrocortisone is normally appropriate. In
other conditions, a pharmacologic dose (any dose in
excess of the replacement dose) is called for. The
equivalent doses of corticosteroids are as follows:

observed, the dose should be carefully reduced to the
lowest dose that will provide adequate control. If no
response is seen after a reasonable period of time, an
alternative method of treatment should be considered.
On rare occasions, patients will respond better to one
corticosteroid than to others.
In the case of acute exacerbations of multiple
sclerosis, doses as high as 200 milligrams of prednisone
or prednisolone for a week followed by 80 mg every
other day for one month have been used.
Because administration of corticosteroids reduces
the output of cortisone from the adrenal glands, dosing
should be designed to minimize the effects of corticosteroid therapy on the adrenal glands. For patients who
will be taking corticosteroids for a long time, a single
dose of the corticosteroid is taken every other morning.
This regimen provides benefits for most conditions,
while minimizing many adverse effects of long-term
steroid administration, including adrenal suppression
and protein breakdown. Although alternate day treatment is the preferred dosing schedule, it is not suited for
treatment of rheumatoid arthritis or ulcerative colitis,
for which daily doses are essential. Only the shorter
acting corticosteroids such as prednisone or prednisolone should be used for alternate-day dosing.
When corticosteroid treatment is being discontinued, it is frequently useful to reduce the dose
gradually, over several days. Many of these tapering
schedules have been described. In one tapering schedule glucocorticoid dosage is reduced by the equivalent of 2.5–5 mg of prednisone every three to seven
days until the physiologic dose (e.g., 5 mg of prednisone or prednisolone, 0.75 mg of dexamethasone, or
20 mg of hydrocortisone) is reached. Other schedules
may call for slower dose adjustments. The dose may
have to be increased if there is a flare-up of the
condition being treated while the dose is being
reduced. Then, tapering may begin again, but at a
slower rate.



cortisone: 25 mg



hydrocortisone: 20 mg



prednisolone: 5 mg



prednisone: 5 mg



methylprednisolone: 4 mg



triamcinolone: 4 mg



dexamethason: 0.75 mg



betamethasone: 0.6 mg

Because corticosteroids reduce the immune
response, they should not be used in patients who
have active fungal infections. Similarly, patients
being treated with corticosteroids should avoid receiving live virus vaccines.

For short-term use, corticosteroids are normally
administered in two or three doses each day. In most
cases, an initial dose equivalent to 5 to 60 milligrams of
prednisone per day is appropriate. Usually, a response
will be seen within ten days. Once a response has been

Corticosteroids may mask some signs of infection,
and new infections may appear during their use. There
may be decreased resistance and inability to localize
infection. Any evidence of infection should be treated
promptly with appropriate anti-infective therapy.

GALE ENCYCLOPEDIA OF MEDICINE

Precautions

1031

Corticosteroids, systemic

unless it is used in combination with a mineralocorticoid drug. Prednisolone is very similar to prednisone.
In addition to oral dosage form, it is available for
subcutaneous, intramuscular, and intravenous
injection.

Corticosteroids, systemic

Corticosteroids may activate latent amebic infections. Therefore, it is recommended that latent or
active amebiasis be ruled out before starting corticosteroid therapy in any patient who has spent time in the
tropics or any patient with unexplained diarrhea.
Adequate human reproduction studies have not
been done with corticosteroids. Use of these drugs in
pregnancy or in women of childbearing potential
requires that the anticipated benefits be weighed against
the possible hazards to the mother and embryo or fetus.
Infants born of mothers who have received substantial
doses of corticosteroids during pregnancy should be
carefully observed for signs of hypoadrenalism.
Corticosteroids have been associated with an
increased risk of gastric ulcers, and patients are usually
advised to take these drugs either with food or a drug
which inhibits gastric acid. Those taking high dose
steroids or on maintenance therapy should take the
medication with meals or a gastric acid blocker to
reduce the risk of gastric ulcers. However, these precautions are probably not needed for patients taking
low doses for a short period of time.

Side effects
Corticosteroids are generally safe when used for a
short period of time with appropriate monitoring.
When used for longer periods, the frequency and
severity of adverse effects increases dramatically.
Many of these effects are the unavoidable results of
the normal actions of the steroid drugs and must be
considered when people decide on a course of longterm corticosteroid therapy.
Fluid and electrolyte disturbances
Sodium retention, fluid retention, congestive heart
failure in susceptible patients, potassium loss, calcium
loss, hypertension may result from long-term use.
Muscle and bone
Muscle weakness, loss of muscle mass, osteoporosis, compression fractures of the spine, aseptic necrosis
of femoral and humeral heads, pathologic fracture of
long bones, and tendon rupture are all possible effects
from long-term use.
Gastrointestinal effects
Peptic ulcer with possible perforation and hemorrhage, perforation of the small and large bowel particularly in patients with inflammatory bowel disease,
pancreatitis, abdominal distention, and ulcerative esophagitis can result from long-term use.
1032

Skin reactions
Impaired wound healing, thin fragile skin, red
spots, increased sweating, reduced reactions to
skin tests, along with other reactions, including
rashes, itching and swelling can all result from
long-term use.
Nerves and central nervous system
Convulsions, increased intracranial pressure with
papilledema (pseudotumor cerebri) usually after treatment, dizziness and loss of balance, headache, and
emotional disturbances can result from long-term use.
Endocrine gland system
Menstrual irregularities, development of cushingoid state, suppression of growth in children, secondary adrenocortical and pituitary unresponsiveness
(particularly in times of stress, as in trauma, surgery,
or illness), decreased carbohydrate tolerance, manifestations of latent diabetes mellitus, hyperglycemia,
increased requirements for insulin or oral hypoglycemic agents in diabetics, and increased hair growth can
result from long-term use.
Eye problems
Cataracts, increased intraocular pressure, glaucoma, and bulging eyes can result from long-term use.
Other problems
Hypersensitivity, blood clotting problems, weight
gain, increased appetite, nausea, and hiccups can result
from long-term use.
In addition to this incomplete list of long-term
effects, other serious effects have been associated
with systemic corticosteroid treatment. The severity
and likelihood of adverse effects increases both with
dose and duration of treatment. Because of their
greater effects on sodium and water, the natural corticosteroids, cortisone, and hydrocortisone are more
likely to cause fluid and electrolyte problems than
the pure glucocorticoids such as dexamethasone and
betamethasone.

Interactions
Drugs that stimulate liver enzymes such as phenobarbital, phenytoin, and rifampin may increase the
rate of elimination of corticosteroids and may require
increases in corticosteroid dose to achieve the desired
response.
GALE ENCYCLOPEDIA OF MEDICINE

Crohn’s disease—A chronic inflammatory disease of
unknown cause, involving any part of the gastrointestinal tract from mouth to anus, but commonly
involving the large intestine, with scarring and thickening of the bowel wall. Crohn’s disease frequently
leads to intestinal obstruction and has a high rate of
recurrence after treatment.
Erythema multiforme—A type of hypersensitivity
(allergic) reaction that occurs in response to medications, infections, or illness. Medications associated
with erythema multiforme include sulfonamides,
penicillins, barbiturates, and phenytoin. Associated
infections include herpes simplex and mycoplasma
infections. In severe cases, the condition is called
Stevens-Johnson syndrome.
Erythroblastopenia—A deficiency in the cells that
create red blood cells. This condition may be severe
and life-threatening, but there is a transient form,
seen in young children, which resolves spontaneously and does not recur.
Hypercalcemia—An excessive amount of calcium in
the blood. The most common cause an excess hormone secretion from the parathyroid gland, but
hypercalcemia may also be seen in some cancers
(lung, breast, multiple myeloma), as a side effect of
some drugs, or from excess calcium in the diet.

course and often remains confined to the skin. Over
time, in about 10% of cases, it can progress to the
lymph nodes and internal organs.
Optic neuritis—Inflammation of the optic nerve (cranial nerve II) which connects to the retina of the eye.
This variable condition can be present with any of the
following symptoms: blurred vision, loss of visual
acuity, loss of some or all color vision, complete or
partial blindness, and pain behind the eye.
Pemphigus—An autoimmune disorder in which the
immune system produces antibodies against specific
proteins in the skin and mucous membrane. These
antibodies produce a reaction that leads to a separation of skin cells.
Pneumonitis (aspiration)—Inflammation of the lung
caused by inhaling a liquid, usually carbon based.
Stevens-Johnson syndrome—A severe form of
erythema multiforme in which the systemic symptoms are severe and the lesions extensive, involving
multiple body areas, especially the mucous
membranes.
Trichinosis—A roundworm infection, usually contracted by eating raw or undercooked meat.
Trichinosis is rare in the United States but a common
infection in some parts of the world.

Mycosis fungoides—The most common type of cutaneous T-cell lymphoma. This low-grade lymphoma
primarily affects the skin. Generally, it has a slow

Ulcerative colitis—A chronic, episodic, inflammatory disease of the large intestine and rectum characterized by bloody diarrhea.

Drugs such as troleandomycin and ketoconazole
may reduce the rate of metabolism of corticosteroids
and decrease the rate of elimination. Therefore, the
dose of corticosteroid should be lowered to avoid
steroid toxicity.

Resources

Corticosteroids may increase the rate of elimination of chronic high dose aspirin. This effect could
lead to decreased salicylate serum levels or increase
the risk of salicylate toxicity when corticosteroid is
withdrawn.
The effects of corticosteroid treatment on anticoagulants vary. There have been reports of both
increased anticoagulant activity and decreased
anticoagulant activity. Careful monitoring is essential when corticosteroids are used together with
anticoagulants.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., ed. Merck Manual of Medical Information:
Home Edition. Riverside, NJ: Simon & Schuster, 2004.
Physicians’ Desk Reference 2005. Montvale, NJ: Thomson
Healthcare, 2004.
PERIODICALS

Cavaliere, F., et al. ‘‘New indications for corticosteroids in
intensive care units.’’ Current Drug Targets 5 (July
2004): 411–7.
Loo, W. J., and N. P. Burrows. ‘‘Management of autoimmune skin disorders in the elderly.’’ Drugs & Aging 12
(2004): 767–77.
Lundberg, I. E., et al. ‘‘Corticosteroids—from an idea to
clinical use.’’ Drugs 64 (2004): 2399–416.
Schlesinger, N. ‘‘Management of acute and chronic gouty
arthritis: present state-of-the-art.’’ Best Practice
1033

Corticosteroids, systemic

KEY TERMS

Cortisol tests

Research Clinical Rheumatology 18, no. 1 (February
2004): 7–19.
ORGANIZATION

American Association of Immunologists Inc. 9650 Rockville
Pike, Bethesda, MD 20814. (301) 634-7178.
<www.aai.org/>.
Arthritis National Research Foundation. 200 Oceangate,
Suite 830, Long Beach, CA 90802. (800) 588-2873.
<www.curearthritis.org/>.

Samuel D. Uretsky, Pharm.D.

Corticotropin test see Adrenocorticotropic
hormone test

I Cortisol tests
Definition
This test is a measure of serum cortisol (also
known as hydrocortisone), or urine cortisol, (also
known as urinary free cortisol), an important hormone produced by a pair of endocrine glands called
the adrenal glands.

Purpose
This test is performed on patients who may have
malfunctioning adrenal glands. Blood and urine cortisol, together with the determination of adrenocorticotropic hormone (ACTH), are the three most important
tests in the investigation of Cushing’s syndrome
(caused by an overproduction of cortisol) and
Addison’s disease (caused by the underproduction of
cortisol).

Precautions
Increased levels of cortisol are associated with pregnancy. Physical and emotional stress can also elevate
cortisol levels. Drugs that may cause increased levels of
cortisol include estrogen, oral contraceptives, amphetamines, cortisone, and spironolactone (Aldactone).
Drugs that may cause decreased levels include androgens, aminoglutethimide, betamethasone, and other
steroid medications, danazol, lithium, levodopa, metyrapone and phenytoin (Dilantin).

Description
Cortisol is a potent hormone known as a glucocorticoid that affects the metabolism of carbohydrates,
1034

proteins, and fats, but especially glucose. Cortisol
increases blood sugar levels by stimulating the release
of glucose from glucose stores in cells. It also acts to
inhibit insulin, thus affecting glucose transport into cells.
The hypothalamus (an area of the brain), the
pituitary gland (sometimes called the ‘‘master
gland’’), and the adrenal glands coordinate the production of cortisol. After corticotropin-releasing hormone (CRH) is made in the hypothalamus, CRH
stimulates the pituitary to produce adrenocorticotropic hormone (ACTH). The production of ACTH in
turn stimulates a part of the adrenal glands known as
the adrenal cortex to produce cortisol. Rising levels of
cortisol act as a negative feedback to curtail further
production of CRH and ACTH, thus completing an
elaborate feedback mechanism.
There are two methods for evaluating cortisol:
blood and urine. The most reliable index of cortisol
secretion is the 24-hour urine sample collection, but
when blood levels are required or requested by the
physician, plasma cortisol should be measured in the
morning and again in the afternoon. Cortisol levels
normally rise and fall during the day in what is called a
diurnal variation, so that cortisol is at its highest level
between 6–8 A.M. and gradually falls, reaching its
lowest point around midnight. One reason for ordering blood cortisol levels versus a 24-hour urine collection is that sometimes the earliest sign of adrenal
malfunction is the loss of this diurnal variation, even
though the cortisol levels are not yet elevated. For
example, individuals with Cushing’s syndrome often
have upper normal plasma cortisol levels in the morning and exhibit no decline as the day progresses.

Preparation
When testing for cortisol levels through the blood,
a blood specimen is usually collected at 8 A.M. and
again at 4 P.M. It should be noted that normal values
may be transposed in individuals who have worked
during the night and slept during the day for long
periods of time.
When testing for cortisol level through the urine, a
24-hour urine sample is collected, refrigerated, and
sent to the reference laboratory for examination.

Risks
Risks for the blood test are minimal, but may
include slight bleeding from the blood-drawing site,
fainting or feeling lightheaded after venipuncture, or
hematoma (blood accumulating under the puncture
site).
GALE ENCYCLOPEDIA OF MEDICINE

Addison’s disease—A rare disorder in which symptoms are caused by a deficiency of hydrocortisone
(cortisol) and aldosterone, two corticosteroid hormones normally produced by a part of the adrenal
glands called the adrenal cortex. Symptoms include
weakness, tiredness, vague abdominal pain, weight
loss, skin pigmentation and low blood pressure.
Adrenal glands—A pair of endocrine glands
(glands that secrete hormones directly into the
bloodstream) that are located on top of the kidneys.
Adrenocorticotropic hormone (ACTH)—Also
called corticotropin, this hormone is produced by
the pituitary gland to stimulate the adrenal cortex to
release various corticosteroid hormones.
Cushing’s syndrome—A hormonal disorder caused
by an abnormally high level of corticosteroid hormones that are produced by the adrenal glands.
Corticosteroid hormones control the body’s use of
nutrients and the excretion of salts and water in the
urine. Symptoms include high blood sugar levels, a
moon face, weight gain, and increased blood
pressure

Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

I Cosmetic dentistry
Definition
Cosmetic dentistry includes a variety of dental
treatments aimed at improving the appearance of the
teeth.

Purpose
The purpose of cosmetic dentistry is to improve
the appearance of the teeth using bleaching, bonding,
veneers, reshaping, orthodontics, or implants.

Description
Normal results
Reference ranges for cortisol vary from laboratory to laboratory but are usually within the following
ranges for blood:


adults (8 A.M.): 6–28 mg/dL; adults (4
2–12 mg/dL

P.M.):



child one to six years (8 A.M.): 3–21 mg/dL; child one
to six years (4 P.M.): 3–10 mg/dL



newborn: 1/24 mg/dL.

Reference ranges for cortisol vary from laboratory to laboratory, but are usually within the following
ranges for 24-hour urine collection:


adult: 10–100 mg/24 hours



adolescent: 5–55 mg/24 hours



Child: 2–27 mg/24 hours.

Bleaching is done to lighten teeth that are stained
or discolored. It entails the use of a bleaching solution
applied by a dentist or a gel in a tray that fits over the
teeth used at home under a dentist’s supervision.
Bonding involves applying tooth-colored plastic
putty, called composite resin, to the surface of chipped
or broken teeth. This resin is also used to fill cavities in
front teeth (giving a more natural-looking result) and
to fill gaps between teeth. Veneers are thin, porcelain
shells that cover the front of the teeth. They can
improve the appearance of damaged, discolored, misshapen, or misaligned teeth. Reshaping involves the
removal of enamel from a misshapen tooth so that it
matches other teeth. Orthodontics uses braces to correct the position of crowded or misaligned teeth.
Implants are artificial teeth which are attached directly
to the jaw to replace missing teeth.

Preparation
Abnormal results
Increased levels of cortisol are found in Cushing’s
syndrome, excess thyroid (hyperthyroidism), obesity,
ACTH-producing tumors, and high levels of stress.
GALE ENCYCLOPEDIA OF MEDICINE

Bleaching involves having a custom-made bleaching tray made by the dentist. This tray is worn at home
for several hours each day or night. Teeth slowly
become white over a period of one to six weeks.
1035

Cosmetic dentistry

Decreased levels of cortisol are found in Addison’s
disease, conditions of low thyroid, and hypopituitarism, in which pituitary activity is diminished.

KEY TERMS

Costochondritis

Bleaching can also be done in a dentist’s office. A heator light-activated bleaching solution is applied to six
to eight teeth per visit.

KEY TERMS

Bonding involves etching the surface of the tooth
so composite resin can adhere. The dentist then contours the resin to the right shape, and smooths and
polishes the resin after it is hard and dry.

Bleaching—Technique used to brighten stained
teeth.
Bonding—Rebuilding, reshaping, and covering
tooth defects using tooth-colored materials.

To prepare for the application of a veneer, a thin
layer of enamel is removed from the tooth (so that the
finished tooth will be flush with surrounding teeth)
and an impression of the tooth is taken from which
the veneer will be created. Before a veneer is applied,
the tooth is etched with an acid solution and an adhesive resin is painted on the tooth. The veneer is then
applied, the resin is hardened with a bonding light, and
the dentist polishes the veneer.
During cosmetic reshaping, some enamel is
removed from the uneven tooth so it more closely
matches other teeth.
Orthodontics involves applying braces to the
teeth, and wires are threaded through the braces.
These wires are adjusted to gradually move the teeth
to the desired new positions. Over time, crowded or
misaligned teeth are straightened.
Implants are more secure and natural looking
than dentures or bridgework, but are much more
expensive. First, an anchor for the implant is attached
to the jaw bone. This surgery can take several hours.
About six months later, after the bone around the
anchor has healed, a post is attached to the anchor,
and an artificial tooth is attached to the post. The
whole process may take about nine months to
complete.

Composite resin—Plastic material matching natural
tooth color used to replace missing parts of a tooth.

while teeth are being bleached, but the sensitivity usually
disappears shortly after completion of the treatment.
Bonded teeth, like bleached teeth, may also stain
more easily than natural teeth. Bonding materials also
chip easily.
Because cosmetic reshaping involves the removal
of enamel, the process is irreversible because enamel
cannot be replaced once it is removed.
The anchors of implanted teeth can loosen and
cause pain; regular dental checkups are recommended.

Normal results
Cosmetic dentistry can improve the appearance of
stained, chipped, misshapen, or crowded teeth.
Resources
ORGANIZATIONS

American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.

Joseph Knight, PA

Aftercare
Periodic touch-up may be needed to keep the teeth
white if the teeth have been bleached or bonded. Also,
the resin used in bonded teeth can be chipped by ice,
popcorn kernels, or hard candy, requiring repair.
Veneered teeth may need to be reveneered after five
to 12 years. Once orthodontic braces are removed,
regular visits to the orthodontist are advised because
teeth can shift position. Implanted teeth require regular dental checkups to ensure that the anchor and
post are stable.

Cosmetic surgery see Plastic, cosmetic,
and reconstructive surgery

I Costochondritis
Definition

Risks
After teeth are bleached, they may darken faster if
exposed to staining products such as coffee or tobacco.
Some patients experience increased sensitivity to cold
1036

Costochondritis is an inflammation and associated tenderness of the cartilage (i.e., the costochondral joints) that attaches the front of the ribs to the
breastbone.
GALE ENCYCLOPEDIA OF MEDICINE

Costochondritis causes pain in the lower rib area
or upper breastbone. Some patients fear they are
having a heart attack. The most severe pain is usually
between the breast and the upper abdomen. The pain
may be greater when in sitting or reclining positions.
Stress may aggravate this condition. Generally the
third or fourth ribs are affected. However, any of the
seven costochondral junctions may be affected, and
more often than not more than one site is involved.
The inflammation can involve cartilage areas on
both sides of the sternum, but usually is on one side
only. Costochondritis should be distinguished from
Tietze Syndrome, which is an inflammation involving the same area of the chest, but also includes
swelling.

Causes and symptoms
The causes of costochondritis are not well-understood and may be difficult to establish. The most likely
causes include injury, repetitive minor trauma, and
unusual excessive physical activity.
The primary symptom of costochondritis is severe
chest wall pain, which may vary in intensity. The pain
becomes worse with trunk movement, deep breathing,
and/or exertion, and better with decreased movement,
quiet breathing, or changing of position. It is usually
localized but may radiate extensively from the chest
area. The pain has been described as sharp, nagging,
aching, or pressure-like.

Diagnosis
Diagnosis is based on pain upon palpation (gentle pressing) of the affected joints. Swelling is not
associated with costochondritis. Diagnosis is also
dependent on the exclusion of other causes, including heart attack or bacterial or fungal infections
found in IV drug users or postoperative thoracic
surgery patients.

Treatment
The goals of treatment are to reduce inflammation
and to control pain. To accomplish these goals, nonsteroidal anti-inflammatory agents (NSAIDs) are
used, with ibuprofen usually selected as the drug of
choice. Other NSAIDS options are flurbiprofen,
mefenamic acid, ketoprofen, and naproxen.
Additional treatment recommendations include the
use of local heat, biofeedback, and gentle stretching
of the pectoralis muscles two to three times a day.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Inflammation— Process whereby the immune system reacts to infection or other stimulus, characterized by pain, swelling, redness, and warmth of the
affected part

For more difficult cases, where the patient continues to exhibit pain and discomfort, cortisone injections are used as therapy.

Alternative treatment
Supplements that are used to reduce inflammation have been used to treat costochondritis. Examples
of such supplements include ginger root, evening
primrose oil, bromelain, vitamin E, omega-3 oils,
and white willow bark. Glucosamine/chondroitin sulfate, which may aid in the healing of cartilage, has also
been used. Other alternative therapies include acupuncture and massages.

Prognosis
The prognosis for recovery from costochondritis
is good. For most patients, the condition lessens in six
months to a year. However, after one year, about onehalf of patients continue with some discomfort, while
about one-third still report tenderness with palpation.

Prevention
Though the causes of costochondritis are not well
known, avoidance of activities that may strain (e.g.,
the repetitive misuse of muscles) or cause trauma to
the rib cage is recommended to prevent the occurrence
of costochondritis. Modification of improper posture
or ergonomics of the home or work place may also
deter the development of this condition.
Resources
OTHER

Day, C. Costochondritis Web Site. 2001. <http://www.geocities.com/Hots/2338/
#Frequently%20Asked%20Questions>.
Flowers, L. K., and B. D. Wippermann. ‘‘Costochondritis.’’
eMedicine Journal: Emergency Medicine/
Rheumatology. February 23, 2001. <http://www.emedicine.com/emerg/topic116.htm>.

Judith Sims
1037

Costochondritis

Description

Cough

Cotrel-Dubousset spinal instrumentation see
Spinal instrumentation

I Cough
Definition
A cough is a forceful release of air from the lungs
that can be heard. Coughing protects the respiratory
system by clearing it of irritants and secretions.

Causes and symptoms
In the majority of cases, coughs are caused by
respiratory infections, including:


colds or influenza, the most common causes of
coughs



bronchitis, an inflammation of the mucous membranes of the bronchial tubes



croup, a viral inflammation of the larynx, windpipe,
and bronchial passages that produces a bark-like
cough in children



whooping cough, a bacterial infection accompanied
by the high-pitched cough for which it is named



pneumonia, a potentially serious bacterial infection
that produces discolored or bloody mucus



tuberculosis, another serious bacterial infection that
produces bloody sputum



fungal infections, such as aspergillosis, histoplasmosis, and cryptococcoses

Description
While people can generally cough voluntarily, a
cough is usually a reflex triggered when an irritant
stimulates one or more of the cough receptors found
at different points in the respiratory system. These
receptors then send a message to the cough center in
the brain, which in turn tells the body to cough. A
cough begins with a deep breath in, at which point
the opening between the vocal cords at the upper
part of the larynx (glottis) shuts, trapping the air
in the lungs. As the diaphragm and other muscles
involved in breathing press against the lungs,
the glottis suddenly opens, producing an explosive
outflow of air at speeds greater than 100 mi (160 km)
per hour.
In normal situations, most people cough once or
twice an hour during the day to clear the airway of
irritants. However, when the level of irritants in the air
is high or when the respiratory system becomes
infected, coughing may become frequent and prolonged. It may interfere with exercise or sleep, and it
may also cause distress if accompanied by dizziness,
chest pain, or breathlessness. In the majority cases,
frequent coughing lasts one to two weeks and tapers
off as the irritant or infection subsides. If a cough lasts
more than three weeks it is considered a chronic
cough, and physicians will try to determine a cause
beyond an acute infection or irritant.
Coughs are generally described as either dry or
productive. A dry cough does not bring up a mixture
of mucus, irritants, and other substances from the
lungs (sputum), while a productive cough does. In
the case of a bacterial infection, the sputum brought
up in a productive cough may be greenish, gray, or
brown. In the case of an allergy or viral infection it
may be clear or white. In the most serious conditions,
the sputum may contain blood.
1038

Environmental pollutants, such as cigarette
smoke, dust, or smog, can also cause a cough. In the
case of cigarette smokers, the nicotine present in the
smoke paralyzes the hairs (cilia) that regularly flush
mucus from the respiratory system. The mucus then
builds up, forcing the body to remove it by coughing.
Post-nasal drip, the irritating trickle of mucus from the
nasal passages into the throat caused by allergies or
sinusitis, can also result in a cough. Some chronic
conditions, such as asthma, chronic bronchitis,
emphysema, and cystic fibrosis, are characterized in
part by a cough. A condition in which stomach acid
backs up into the esophagus (gastroesophageal reflux)
can cause coughing, especially when a person is lying
down. A cough can also be a side-effect of medications
that are administered via an inhaler. It can also be a
side-effect of beta-blockers and ACE inhibitors, which
are drugs used for treating high blood pressure.

Diagnosis
To determine the cause of a cough, a physician
should take an exact medical history and perform an
exam. Information regarding the duration of the
cough, other symptoms may accompanying it, and
environmental factors that may influence it aid the
doctor in his or her diagnosis. The appearance of the
sputum will also help determine what type of infection,
if any, may be involved. The doctor may even observe
the sputum microscopically for the presence of bacteria and white blood cells. Chest x rays may help
indicate the presence and extent of such infections as
pneumonia or tuberculosis. If these actions are not
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Treatment of a cough generally involves addressing the condition causing it. An acute infection such
as pneumonia may require antibiotics, an asthmainduced cough may be treated with the use of bronchodialators, or an antihistamine may be administered in
the case of an allergy. Physicians prefer not to suppress
a productive cough, since it aids the body in clearing
the respiratory system of infective agents and irritants.
However, cough medicines may be given if the patient
cannot rest because of the cough or if the cough is not
productive, as is the case with most coughs associated
with colds or flu. The two types of drugs used to treat
coughs are antitussives and expectorants.
Antitussives
Antitussives are drugs that suppress a cough.
Narcotics—primarily codeine—are used as antitussives
and work by depressing the cough center in the brain.
However, they can cause such side effects as drowsiness,
nausea, and constipation. Dextromethorphan, the primary ingredient in many over-the-counter cough remedies, also depresses the brain’s cough center, but
without the side effects associated with narcotics.
Demulcents relieve coughing by coating irritated
passageways.
Expectorants
Expectorants are drugs that make mucus easier to
cough up by thinning it. Guaifenesin and terpin
hydrate are the primary ingredients in most over-thecounter expectorants. However, some studies have
shown that in acute infections, simply increasing
fluid intake has the same thinning effect as taking
expectorants.

Alternative treatment
Coughs due to bacterial or viral upper respiratory
infections may be effectively treated with botanical
and homeopathic therapies. The choice of remedy
will vary and be specific to the type of cough the
patient has. Some combination over-the-counter herbal and homeopathic cough formulas can be very
effective for cough relief. Lingering coughs or coughing up blood should be treated by a trained
practitioner.
GALE ENCYCLOPEDIA OF MEDICINE

Cough

enough to determine the cause of the cough, a bronchoscopy or laryngoscopy may be ordered. These tests use
slender tubular instruments to inspect the interior of
the bronchi and larynx.

KEY TERMS
Antitussives—Drugs used to suppress coughing.
Expectorant—Drug used to thin mucus.
Gastroesophageal reflux—Condition in which stomach acid backs up into the esophagus.
Glottis—The opening between the vocal cords at
the upper part of the larynx.
Larynx—A part of the respiratory tract between the
pharynx and the trachea, having walls of cartilage
and muscle and containing the vocal cords.
Sputum—The mixture of mucus, irritants, and other
substances expelled from the lungs by coughing.

Many health practitioners advise increasing fluids
and breathing in warm, humidified air as ways of
loosening chest congestion. Others recommend hot
tea flavored with honey as a temporary home remedy
for coughs caused by colds or flu. Various vitamins,
such as vitamin C, may be helpful in preventing or
treating conditions (including colds and flu) that lead
to coughs. Avoiding mucous-producing foods can be
effective in healing a cough condition. These mucousproducing foods can vary, based on individual
intolerance, but dairy products are a major mucousproducing food for most people.

Prognosis
Because the majority of coughs are related to the
common cold or influenza, most will end in seven to
21 days. The outcome of coughs due to a more serious
underlying disease depends on the pathology of that
disease.

Prevention
It is important to identify and treat the underlying
disease and origin of the cough. Avoiding smoking
and direct contact with people experiencing cold or
flu symptoms is recommended. Washing hands frequently during episodes of upper-respiratory illnesses
is advised. Parents should follow recommended vaccination schedules for pertussion (whooping cough) to
help prevent the disease from occurring.
Resources
PERIODICALS

‘‘Whooping Cough on the Rise.’’ Consumer Reports May
2004: 51.
1039

Cough suppressants

ORGANIZATIONS



children two to six: 2.5–7.5 mg every four to eight
hours, as needed (Children under six should not
be given lozenges containing dextromethorphan
because of the high dose of dextromethorphan in
each lozenge.)



children under two: check with child’s physician

National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Jeffrey P. Larson, RPT
Teresa G. Odle

For extended-release oral suspension:

I Cough suppressants
Definition
Cough suppressants are medicines that prevent or
stop coughing.

Purpose
Cough suppressants act on the center in the brain
that controls the cough reflex. They are meant to be
used only to relieve dry, hacking coughs associated
with colds and flu. They should not be used to treat
coughs that bring up mucus or the chronic coughs
associated with smoking, asthma, emphysema or
other lung problems.
Many cough medicines contain cough suppressants along with other ingredients. Some combinations of ingredients may cancel each other’s effects.
One example is the combination of cough suppressant
with an expectorant—a medicine that loosens and
clears mucus from the airways. The cough suppressant
interferes with the ability to cough up the mucus that
the expectorant loosens.

Description
The cough suppressant described here, dextromethorphan, is an ingredient in many cough medicines, such as Vicks Formula 44, Drixoral Cough
Liquid Caps, Sucrets Cough Control, Benylin DM
and some Robitussin products. These medicines
come in capsule, tablet, lozenge, and liquid forms
and are available without a physician’s prescription.
Recommended dosage:
Regular (short-acting) capsules, lozenges, syrups,
or tablets:


adults and children over 12: 10–30 mg every four to
eight hours, as needed



children six to 12: 5–15 mg every four to eight hours,
as needed

1040



adults and children over 12: 60 mg every 12 hours, as
needed



children six to 12: 30 mg every 12 hours, as needed



children two to six: 15 mg every 12 hours, as needed



children under two: check with child’s physician

Precautions
Do not take more than the recommended daily
dosage of dextromethorphan.
Dextromethorphan is not meant to be used for
coughs associated with smoking, asthma, emphysema,
chronic bronchitis, or other lung conditions. It also
should not be used for coughs that produce mucus.
A lingering cough could be a sign of a serious
medical condition. Coughs that last more than seven
days or are associated with fever, rash, sore throat, or
lasting headache should have medical attention. Call a
physician as soon as possible.
People with phenylketonuria should be aware that
some products with dextromethorphan also contain
the artificial sweetener aspartame, which breaks down
in the body to phenylalanine.
Anyone who has asthma or liver disease should
check with a physician before taking dextromethorphan.
Women who are pregnant or breastfeeding or who
plan to become pregnant should check with their physicians before taking dextromethorphan.
The dye tartrazine is an ingredient in some cough
suppressant products. This dye causes allergic reactions in
some people, especially those who are allergic to aspirin.

Side effects
Side effects are rare, but may include nausea,
vomiting, stomach upset, slight drowsiness, and
dizziness.

Interactions
Patients who take monoamine oxidase inhibitors
(MAO inhibitors) should be aware that the
co-administration
of
products
containing
GALE ENCYCLOPEDIA OF MEDICINE

Asthma—A disease in which the air passages of the
lungs become inflamed and narrowed.
Bronchitis—Inflammation of the air passages of the
lungs.
Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Emphysema—An irreversible lung disease in which
breathing becomes increasingly difficult.
Mucus—Thick fluid produced by the moist membranes that line many body cavities and structures.
Phenylketonuria (PKU)—A genetic disorder in
which the body lacks an important enzyme. If
untreated, the disorder can lead to brain damage
and mental retardation.

dextromethorphan can cause dizziness, fainting,
fever, nausea and possibly coma. Do not take dextromethorphan unless a physician permits the use of the
two drugs together.
When dextromethorphan is taken with medicines
that cause drowsiness, this effect may be enhanced.

Coughing and deep-breathing exercises see
Chest physical therapy

I Couvade syndrome
Definition
Couvade syndrome, which is also known as sympathetic pregnancy, male pregnancy experience, or
‘‘pregnant dad syndrome,’’ refers to a condition in
which a father-to-be experiences some of the physical
symptoms of pregnancy prior to the baby s birth. The
term couvade comes from the French verb couver,
which means ‘‘to brood,’’ in the sense of a bird protecting its eggs before they hatch.

different historical periods as well as various cultures
around the world, ranging from ancient Greece and
parts of the Roman Empire to Chinese Turkestan, the
Basque regions of northern Spain, China, Thailand,
Borneo, parts of Russia, and many Indian tribes in
North as well as South America. In some cultures the
expectant father avoids eating certain foods or handling knives or other sharp tools while the mother is in
labor. In Papua New Guinea the father builds a hut
apart from the rest of the village and goes to bed when
his wife s childbirth begins. He then stays in bed and
imitates the pains of childbirth until the baby is born.
A similar custom is observed among the Basques.
Couvade rituals are thought to have a number of
possible purposes, depending on the specific culture:


To draw the attention of evil spirits away from the
mother to the father instead.



To strengthen the emotional bond between father
and child.



To show that the man is the child’s biological father.



To relieve the father’s anxiety while the mother is in
labor.



To strengthen the father’s relationship with supernatural beings so that he can guide the child into the
world.

Ritual couvade is no longer observed in most
developed countries, but the term couvade syndrome
has been applied to the physical symptoms that many
men in these countries experience during a wife’s pregnancy, ranging from mild nausea or backaches to
weight gain or toothache. One group of Italian
researchers reported that the number of men who
experience couvade syndrome ranges between 11 and
65 percent, while others estimate that as many as 80
percent of expectant fathers develop these symptoms.
It is thought that more men in Western societies
experience couvade syndrome in the early 2000s than
was the case with previous generations of fathers, due
in part to changes in men s involvement with the birthing process. Some doctors think that the participation
of fathers in the delivery room as ‘‘coaches’’ or comforters is one reason for the increased number of men
who develop pregnancy symptoms.

Causes and symptoms
Causes

Description
The term couvade was first used by the anthropologist E. B. Tylor in 1865 to describe certain fatherhood rituals performed by husbands while their wives
were giving birth. These rituals were found in many
GALE ENCYCLOPEDIA OF MEDICINE

Several different types of explanation have been
proposed for couvade syndrome:


It is a psychiatric disorder. This type of explanation
is more common among European than American
1041

Couvade syndrome

KEY TERMS

Couvade syndrome

physicians. Some attribute the symptoms of couvade
syndrome to jealousy of the woman s ability to give
birth, while others maintain that they result from
male guilt over impregnating the woman or to sibling
rivalry—that is, the husband regards the wife as a
competitor that he must try to outperform.


It results from real biological changes in the expectant father s body. A team of Canadian researchers
reported that their sample of expectant fathers had
higher levels of estradiol (a female hormone) and
lower levels of testosterone (a male sex hormone) in
their blood and saliva than a control group of childless men. The researchers have cautioned, however,
that their findings should be checked by studying
groups of men from other cultures.



It is a reaction to a changed social role; that is, the
syndrome is one way that some men ‘‘work through’’
their feelings about assuming the social expectations
and responsibilities associated with fatherhood.



It is a set of psychosomatic symptoms that is within
the range of normal experience and does not indicate
mental illness. Psychosomatic refers to physical
symptoms that are caused or influenced by emotional factors, such as stress headaches or ‘‘butterflies in the stomach’’ before an examination.
Symptoms

Expectant fathers may experience one or more of
the following:


weight gain



nausea and vomiting



stomach cramps



constipation or diarrhea



loss of appetite



sleep disturbances



food cravings



headaches



toothache



nosebleeds



itchy skin

Only a few men, however, develop the more dramatic symptoms. Some studies report that couvade
syndrome is most severe during the third or fourth
month of the wife s pregnancy and again just before
birth. Some researchers report that the syndrome is
more common in first-time fathers, while others have
found that it is equally likely to develop in men who
already have children.
1042

KEY TERMS
Anthropology—The study of the origins, biological
characteristics, beliefs, and social customs of
human beings.
Psychosomatic—Referring to physical symptoms
that are caused or significantly influenced by emotional factors. Some doctors regard couvade syndrome as a psychosomatic condition.
Syndrome—A set of symptoms that occur together.

Diagnosis
Couvade syndrome is not listed as a diagnostic
category in the most recent editions of the American
Diagnostic and Statistical Manual of Mental
Disorders, fourth edition, text revision (2000) or
the World Health Organization’s International
Classification of Diseases, version 10 (1993). In addition, it is not described or discussed in most medical
textbooks, although a few handbooks for doctors in
family practice mention it in passing as a condition
of unknown origin. Since most men with couvade
syndrome have only mild symptoms, they are unlikely to consult a doctor about the condition by
itself.

Treatment
There is no standard mainstream treatment
recommended for couvade syndrome because it is
not usually mentioned in medical textbooks.
Anecdotal evidence, however, indicates that most
fathers-to-be are helped by a simple explanation of
the syndrome and reassurance that it is not uncommon among American and Canadian men.

Alternative treatment
Some expectant fathers report that meditation or
such movement therapies as yoga and t’ai chi are
calming and relaxing. Peppermint tea or ginger are
herbal remedies that help to relieve nausea.

Prognosis
Couvade syndrome almost always goes away after
the baby is born. While a few instances of the syndrome developing into full-blown psychosis (loss of
contact with reality) have been reported in European
medical journals, such cases are extremely rare.
GALE ENCYCLOPEDIA OF MEDICINE

There is no known way to prevent couvade syndrome as of the early 2000s, as doctors do not yet
understand why some men develop it and others
do not.
Resources
BOOKS

Reed, Richard K. Birthing Fathers: The Transformation of
Men in American Rites of Birth. Piscataway, NJ:
Rutgers University Press, 2005.
PERIODICALS

Budur, K., and M. Mathews. ‘‘Couvade Syndrome
Equivalent?’’ Psychosomatics 46 (January 2005): 71–72.
Mason, C., and R. Elwood. ‘‘Is There a Physiological Basis
for the Couvade and Onset of Paternal Care?’’
International Journal of Nursing Studies 32 (April 1995):
137–148.
Masoni, S., A. Maio, G. Trimarchi, et al. ‘‘The Couvade
Syndrome.’’ Journal of Psychosomatic Obstetrics and
Gynecology 15 (September 1994): 125–131.
Mayer, C., and H. P. Kapfhammer. ‘‘Couvade Syndrome, A
Psychogenic Illness in the Transition to Fatherhood.’’
[in German] Fortschritte der Neurologie-Psychiatrie 61
(October 1993): 354–360.
Reed, Richard. ‘‘Birthing Fathers.’’ Mothering, no. 78
(Spring 1996).
Tenyi, T., M. Trixler, and F. Jadi. ‘‘Psychotic Couvade: 2
Case Reports.’’ Psychopathology 29 (1996): 252–254.
ORGANIZATIONS

American Academy of Family Physicians (AAFP). 11400
Tomahawk Creek Parkway, Leawood, KS 66211-2672.
(800) 274-2237 or (913) 906-6000. <http://
www.aafp.org>.
OTHER

Polinski, Michael. ‘‘Feeling Her Pain: The Male Pregnancy
Experience.’’ Pregnancy Today, <http://www.pregnancytoday.com/reference/articles/malepg.htm>.

Rebecca Frey, PhD

I Cox-2 Inhibitors
Definition
Cox-2 inhibitors are non-steroidal anti-inflammatory drugs (NSAIDs) which selectively inhibit
cyclooxygenase-2. The cyclooxygenases are required
for the creation of prostaglandins. Prostaglandins act
somewhat like hormones in controlling many of the
functions of the body, including control of blood
GALE ENCYCLOPEDIA OF MEDICINE

pressure and control of the smooth muscle of the
respiratory tract and intestines. The traditional
NSAIDs inhibit both cyclooxygenase 1 and 2 (Cox-1
and Cox-2). However, while Cox-2 is associated with
inflammation and pain, Cox-1 maintains the integrity
of the gastric mucosa, mediates normal platelet function, and regulates renal blood flow.
The development of the Cox-2 selective inhibitors
was intended to provide drugs that would offer the
same pain relieving and anti-inflammatory effects as
the traditional NSAIDs without causing the gastric
ulcers that have been associated with the older drugs.

Purpose
Although the non-steroidal anti-inflammatory
drugs are considered relatively safe, they are so widely
used that their adverse effects are significant. As of
2005, they account for almost one-fourth of all
reported adverse drug reactions. Approximately 15%
of NSAID users have gastrointestinal tract symptoms
such as dyspepsia, heartburn, nausea or vomiting. Each
year, 1 to 4% of NSAID users have serious gastrointestinal tract complications such as hemorrhage, with
an estimated cost of $15,000 to $20,000 per hospitalization while an estimated 16,500 NSAID-related
deaths occur annually among patients with osteoarthritis or rheumatoid arthritis.
In early studies, the Cox-2 inhibitors appeared to
be fulfilling their promise. A 1999 study which compared celecoxib (Celebrex) with naproxen (Naprosyn)
and placebo reported that the incidence of gastric
erosions and ulcers was significantly greater in the
naproxen group than in the celecoxib or placebo
group. A 1999 report in The American Journal of
Orthopedics stated: ‘‘Controlled trials have also
shown that the incidence of gastroduodenal ulcers
and the combined incidence of gastroduodenal ulcers
and erosions are significantly lower with celecoxib
therapy than with naproxen therapy and are similar
to those associated with placebo administration. In a
study of platelet function, it was found that a single
650-mg dose of aspirin profoundly diminished platelet
function, while therapeutic doses of celecoxib exhibited no such effect. Celecoxib has been shown to be
well tolerated, with incidences of adverse events similar to placebo in most instances.’’ However, a French
review warned that certain selective Cox-2 inhibitors
(i.e. celecoxib, rofecoxib) have not been tested for
safety on patients with ulcers or cardiovascular or
renal disease.
In 2003, celecoxib was the 28th most prescribed
drug in the United States based on number of
1043

Cox-2 Inhibitors

Prevention

Cox-2 Inhibitors

prescriptions written, while rofecoxib (Vioxx) ranked
36th.
Even so, there were evidences of concern about
the potential risks of the Cox-2 inhibitors. While the
1999 review claimed that the drugs had no effect on
platelet function, a 2002 paper from the University of
Michigan Department of Cardiology warned that the
drugs might increase the risk of blood clotting, and a
Canadian paper, published about the same time,
reported that the efficacy of cycloozygenase inhibitors
did not always match that of conventional nonsteroidal anti-inflammatory drugs
On September 30, 2004, the United States Food
and Drug Administration announced that Merck and
Company was withdrawing rofecoxib from the market, based on evidence from long-term studies showing
that the drug had a higher risk of cardiovascular problems than comparable agents.
On April 7, 2005, the Food and Drug
Administration asked Pfizer to withdraw valdecoxib
(Bextra) from the market. Valdecoxib had been
approved for treatment of rheumatoid and osteoarthritis and for primary dysmenorrhea. The FDA
recommendation for the discontinuation of valdecoxib was based not on cardiovascular safety, but
rather on the relative frequency of rare but very severe
skin reactions, including Steven Johnson syndrome
(SJS) and toxic epidermal necrolysis (TEN). These
potentially fatal adverse reactions are seen with
many drugs in many different classes, but according
to the FDA were observed disproportionately frequently with valdecoxib.
For patients who require NSAIDs but are at risk
of ulcers, a number of approaches are available,
although few appear to hold up to scientific scrutiny.
Although some NSAIDs have made claims of greater
gastrointestinal safety, Canada’s Therapeutics
Initiative failed to find significant advantages to any
NSAID, although some do show a limited safety
advantage in short term use. Salsalate and ibuprofen
were at once the safest and least expensive drugs in the
group.
Misoprostol, a prostaglandin, is an effective gastroprotective agent which has reduced the frequency
of gastric ulcers from 0.95% to 0.57%. Misoprostol is
available by itself or in combination with diclofenac,
under the brand name Arthotec. However, misoprostol is an abortifacient and has been associated with
birth defects. For this reason, it may be inappropriate
for use in women of childbearing potential.
The proton pump inhibitors (esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprozole)
1044

appear to be effective at protecting the stomach; however, more studies are needed. The H-2 receptor blockers (cimetidine, famotidine, nizatidine, and ranitidine)
have not demonstrated activity in ulcer prevention
and are not recommended for this purpose.

Description
The only Cox-2 inhibitor on the market as of
April 2005 is celecoxib (Celebrex).
Celecoxib is indicated for treatment of rheumatoid and osteoarthritis, acute pain and the pain associated with primary dysmenorrhea. The drug is also
used to reduce the number of polyps in familial adenomatous polyposis (FAP). It is not known whether
there is a clinical benefit from a reduction in the number of colorectal polyps in FAP patients or whether
the effects of celecoxib treatment will persist after the
drug is discontinued. The efficacy and safety of celecoxib treatment in patients with FAP beyond 6 months
have not been studied as of April 2005.

Recommended dosage
Celecoxib
Osteoarthritis: 200 mg/day administered as a single dose or as 100 mg twice/day.
Rheumatoid arthritis: 100 to 200 mg twice/day.
Acute pain and primary dysmenorrhea: 400 mg
initially, followed by an additional 200 mg dose if
needed on the first day. On subsequent days, the
recommended dose is 200 mg twice daily as needed.

Precautions
The following rules have applied to all Cox-2
inhibitors that have been marketed:


Should not be used by patients who are allergic to
sulfonamides



Should not be used by patients who have shown
allergic reactions to other non-steroidal anti-inflammatory agents such as ibuprofen of naproxen.



Should not be used in patients who have aspirinassociated asthma.



The use of these drugs is specifically contraindicated
in late pregnancy, since they may cause premature
closure of the ductus arteriosus.



The Cox-2 inhibitors have not been studied in
patients with advanced kidney disease, and their use
is not recommended.
GALE ENCYCLOPEDIA OF MEDICINE

Cyclooxygenase—An enzyme, found in most tissues,
that helps turn some fatty acids into protaglandins.
NSAIDs—A group of drugs that is not formed from
a corticosteroid molecule, but which reduces
inflammation. Most of these drugs also function as
pain relievers and reduce fever as well.
Osteoarthritis—A type of joint deterioration
caused by damage to cartilage.

metabolized by the liver, it will change the normal
blood levels of other drugs that are metabolized in a
similar manner, which may either increase or decrease
the effects of these drugs.
The following is a partial list of drugs that interact
with celecoxib:


Aspirin: Administration of aspirin with Cox-2 inhibitors may result in an increased risk of GI ulceration
and complications.



ACE-inhibitors: Reports suggest that NSAIDs, including the Cox-2 inhibitors, may diminish the antihypertensive effect of ACE-inhibitors. The ACE-inhibitors
include benazepril (Lotensin), captopril (Capoten),
enalapril (Vasotec), fosinopril (Monopril), lisinopril
(Prinivil, Zestril), moexipril (Univasc), perindopril
(Aceon), quinapril (Accupril), ramipril (Altace), and
trandolapril (Mavik).



Furosemide: Clinical studies, as well as post-marketing observations, have shown that NSAIDs can
reduce the sodium removing effect of furosemide
(Lasix) and thiazide diuretics in some patients.



Anticonvulsants (Phenytoin): When these drugs are
used together, the levels of Cox-2 inhibitors may be
reduced by over 25%. A dose adjustment may be
required.



Warfarin: Cox-2 inhibitors may increase the anticlotting effects of warfarin (Coumadin). Patients
taking these drugs together should have their coagulation times closely monitored until the doses can be
adjusted.



Fluconazole and Ketoconazole: These antifungal
drugs are metabolized by the same means as the
Cox-2 inhibitors and cause very significant increases
in the blood levels of celecoxib and valdecoxib. The
doses of the Cox-2 inhibitors may have to be
reduced.



Glyburide: Glyburide (Diabeta, Glynase, and
Micronase) is used to treat diabetes. Whether there
is a drug interaction seems to depend on the dose
levels of the drugs, but at some dosages, the Cox-2
inhibitors may increase the blood levels of glyburide,
leading to a significant drop in blood sugar levels. If
these drugs must be taken together, blood sugar
levels should be closely monitored until the doses of
the two drugs are fully adjusted.

Primary dysmenorrhea—Painful menstruation
caused by inflammation, new growths, or anatomic
factors.
Proton pump inhibitor—One of a group of drugs
that acts to reduce the secretion of stomach acid.
Renal—Relating to the kidneys.
Rheumatoid arthritis—A type of joint deterioration
caused by inflammation.

Side effects
Although the Cox-2 inhibitors cause a lower incidence of ulcers than the non-selective NSAIDs, the
frequency of less severe stomach and intestinal side
effects is similar. The most common side effects of
the Cox-2 inhibitors are: upset stomach, stomach
pain, diarrhea, gas or bloating, and sore throat.
There are a large number of other possible effects,
which although infrequent may be serious and require
prompt medical attention: black and tarry stools, red
blood in stools, bloody vomit, vomiting material that
looks like coffee grounds, excessive tiredness, unusual
bleeding or bruising, itching, lack of energy, loss of
appetite, pain in the upper right part of the stomach,
yellowing of the skin or eyes, flu-like symptoms, rash,
pale skin, unexplained weight gain, swelling of the face,
throat, tongue, lips, eyes, hands, feet, ankles, or lower
legs, hoarseness, difficulty swallowing, or breathing.

Interactions
Celecoxib has the potential for a large number of
drug interactions. Because it has a large number of
possible adverse effects, it may interact with any
other drug that causes a similar effect or increases
the risk or severity of the problem. For example,
since the Cox-2 inhibitors commonly cause stomach
upset, there will be an even greater risk of stomach
distress when celecoxib is taken with another drug that
causes stomach problems. Similarly, since the drug is
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Physicians’ Desk Reference 2005. Montvale, NJ: Thomson
Healthcare, 2004.
1045

Cox-2 Inhibitors

KEY TERMS

Craniosacral therapy

PERIODICALS

Goldenberg, M. M. ‘‘Celecoxib, a selective cyclooxygenase-2
inhibitor for the treatment of rheumatoid arthritis and
osteoarthritis.’’ Clinical Therapy 9 (September 21,
1999): 1497–513
Larousse, C., and G. Veyrac. ‘‘[Clinical data on COX-1 and
COX-2 inhibitors: what possible alerts in pharmacovigilance?]’’ Therapie. 55, no. 1 (January/February 2000):
21–8 (article in French, English abstract).
ORGANIZATION

Arthritis Foundation. PO Box 7669, Atlanta, GA 303570669. (800)568-4045. <www.arthritis.org/>.
Arthritis National Research Foundation 200 Oceangate,
Suite 830, Long Beach, CA 90802. (800)588-2873.
<www.curearthritis.org/>.

Samuel D. Uretsky, Pharm.D.

Coxsackievirus infections see Enterovirus
infections
CPK test see Creatine kinase test
CPR see Cardiopulmonary resuscitation
Crab lice see Lice infestation
Cradle cap see Seborrheic dermatitis
Cramps see Dysmenorrhea

WILLIAM SUTHERLAND
(1873–1954)
William Garner Sutherland studied osteopathy under
its founder, Andrew Taylor Still. Dr. Sutherland made his
own important discovery while examining the sutures of
cranial bones the skull bones that protect the brain. What he
noticed is that the sutures were designed for motion.
Sutherland termed this motion the Breath of Life. Through
his experiments and research he determined that primary
respiration was essential to all other physiological functions.
When Sutherland developed his techniques for
craniosacral therapy, he wanted it to serve as a vehicle
for listening to the body’s rhythmic motions, and treat the
patterns of inertia, when those motions become congested.
He believed that the stresses—any physical or emotional
trauma—created an imbalance in the body that needed
correction to restore it to full health. The therapy is a
hands-on method so that the therapist can feel the subtleties of the patterns of movement and inertia. Sutherland felt
that this was the way to encourage self-healing and restoration of the body’s own mechanisms, taking a holistic
approach to creating optimal health.
The Craniosacral Therapy Educational Trust, based on
Sutherland’s pioneering work is located at 10 Normington
Close, Leigham Court Road, London SW16 2QS, United
Kingdom. The phone number is 07000 785778.

Cranial arteritis see Temporal arteritis
Cranial manipulation see Craniosacral
therapy
Craniopharyngioma see Pituitary tumors

I Craniosacral therapy
Definition
Craniosacral therapy is a holistic healing practice
that uses very light touching to balance the craniosacral system in the body, which includes the bones,
nerves, fluids, and connective tissues of the cranium
and spinal area.

Purpose
According to Dr. John Upledger, craniosacral
therapy is ideally suited for attention-deficit hyperactivity disorder, headaches, chronic middle ear infection, pain, and general health maintenance. It is
recommended for autism, fibromyalgia, heart disease,
osteoarthritis, pneumonia, rheumatoid arthritis,
1046

chronic sinus infections, and gastroenteritis (inflammation of the lining of the stomach or small intestine).
It is also used with other therapies to treat chronic
fatigue syndrome, back pain, and menstrual irregularity. In addition, other craniosacral practitioners
have reported benefits for eye dysfunction, dyslexia,
depression, motor coordination difficulties, temporomandibular joint dysfunction (TMD), hyperactivity,
colic, asthma in babies, floppy baby syndrome, whiplash, cerebral palsy, certain birth defects, and other
central nervous system disorders.

Description
Origins
The first written reference to the movement of the
spinal nerves and its importance in life, clarity, and
‘‘bringing quiet to the heart’’ is found in a 4,000-yearold text from China. Craniosacral work was referred
to as ‘‘the art of listening.’’ Bone setters in the Middle
Ages also sensed the subtle movements of the body.
They used these movements to help reset fractures and
dislocations and to treat headaches.
GALE ENCYCLOPEDIA OF MEDICINE

Dr. John Upledger, an osteopathic physician,
and others at the Department of Biomechanics at
Michigan State University, College of Osteopathic
Medicine learned of Sutherland’s research and developed it further. He researched the clinical observations
of various osteopathic physicians. This research provided the basis for Upledger’s work that he named
craniosacral therapy.
Craniosacral therapy addresses the craniosacral
system. This system includes the cranium, spine, and
sacrum that are connected by a continuous membrane
of connective tissue deep inside the body, called the
dura mater. The dura mater also encloses the brain
and the central nervous system. Sutherland noticed
that cerebral spinal fluid rises and falls within the compartment of the dura mata. He called this movement the
primary respiratory impulse; today it is known as the
craniosacral rhythm (CSR) or the cranial wave.
Craniosacral therapists can most easily feel the
CSR in the body by lightly touching the base of the
skull or the sacrum. During a session, they feel for
disturbances in the rate, amplitude, symmetry, and
quality of flow of the CSR. A therapist uses very gentle
touch to balance the flow of the CSR. Once the cerebrospinal fluid moves freely, the body’s natural healing responses can function.
A craniosacral session generally lasts 30–90 minutes. The client remains fully clothed and lays down on
a massage table while the therapist gently assesses the
flow of the CSR. Upledger describes several techniques which may be used in a craniosacral therapy
session. The first is energy cyst release. According to
Upledger, ‘‘This technique is a hands-on method of
releasing foreign or disruptive energies from the
patient’s body. Energy cysts may cause the disruption
of the tissues and organs where they are located.’’ The
therapist feels these cysts in the client’s body and
gently releases the blockage of energy.
GALE ENCYCLOPEDIA OF MEDICINE

Sutherland first wrote about a second practice
called direction of energy. In this technique the therapist intends energy to pass from one of his hands,
through the patient, into the other hand.
The third technique is called myofascial release.
This is a manipulative form of bodywork that releases
tension in the fascia or connective tissue of the body.
This form of bodywork uses stronger touch.
Upledger’s fourth technique is position of
release. This involves following the client’s body
into the positions in which an injury occurred and
holding it there. When the rhythm of the CSR suddenly stops the therapist knows that the trauma has
been released.
The last technique is somatoemotional release.
This technique was developed by Upledger and is
an offshoot of craniosacral therapy. It is used to
release the mind and body of the residual effects
of trauma and injury that are ‘‘locked in the
tissues.’’
The cost of a session varies due to the length of
time needed and the qualifications of the therapist.
The cost may be covered by insurance when the therapy is performed or prescribed by a licensed health
care provider.

Precautions
This gentle approach is extremely safe in most
cases. However, craniosacral therapy is not recommended in cases of acute systemic infections, recent
skull fracture, intracranial hemorrhage or aneurysm,
or herniation of the medulla oblongata (brain stem).
Craniosacral therapy does not preclude the use of
other medical approaches.

Side effects
Some people may experience mild discomfort
after a treatment. This may be due to re-experiencing
a trauma or injury or a previously numb area may
come back to life and be more sensitive. These side
effects are temporary.

Research and general acceptance
More than 40 scientific papers have been published that document the various effects of craniosacral therapy. There are also 10 authoritative textbooks
on this therapy. The most notable scientific papers
include Viola M. Fryman’s work documenting the
successful treatment of 1,250 newborn children with
birth defects. Edna Lay and Stephen Blood showed the
1047

Craniosacral therapy

In the early 1900s, the research of Dr. William
Sutherland, an American osteopathic physician,
detailed the movement of the cranium and pelvis.
Before his research it was believed that the cranium
was a solid immovable mass. Sutherland reported
that the skull is actually made up of 22 separate
and movable bones that are connected by layers
of tissue. He called his work cranial osteopathy.
Nephi Cotton, an American chiropractor and contemporary of Sutherland, called this approach craniology.
The graduates of these two disciplines have refined and
enhanced these original approaches and renamed their
work as sacro-occipital technique, cranial movement
therapy, or craniosacral therapy.

Craniotomy

effects on TMD, and John Wood documented results
with psychiatric disorders. The American Dental
Association has found craniosacral therapy to be an
effective adjunct to orthodontic work. However, the
conventional medical community has not endorsed
these techniques.
Resources
BOOKS

Upledger, John E. ‘‘CranioSacral Therapy.’’ In Clinician’s
Complete Reference to Complementary and Alternative
Medicine, edited by Donald Novey. C.V. Moskey,
St. Louis: 2000.
ORGANIZATIONS

Milne Institute Inc. P.O. Box 2716, Monterey, CA 939422716. (831) 649-1825. Fax: (831) 649-1826. <http://
www.milneinstitute.com>. milneinst@aol.com.
Upledger Institute. 11211 Prosperity Farms Road, Palm
Beach Gardens, FL 33410. (800) 233-5880. Fax: (561)
622-4771. <http://www.upledger.com>.
OTHER

Milne, Hugh. A Client’s Introduction to Craniosacral Work.
Pamphlet. Milne Institute.

Linda Chrisman

Description
There are two basic ways to open the skull:


a curving incision from behind the hairline, in front
of the ear, arching above the eye



at the nape of the neck around the occipital lobe.

The surgeon marks with a felt tip pen a large square
flap on the scalp that covers the surgical area. Following
this mark, the surgeon makes an incision into the skin as
far as the thin membrane covering the skull bone.
Because the scalp is well supplied with blood, the surgeon will have to seal many small arteries. The surgeon
then folds back a skin flap to expose the bone.
Using a high speed hand drill or an automatic
craniotome, the surgeon makes a circle of holes in the
skull, and pushes a soft metal guide under the bone from
one hole to the next. A fine wire saw is then moved along
the guide channel under the bone between adjacent
holes. The surgeon saws through the bone until the
bone flap can be removed to expose the brain.
After the surgery for the underlying cause is completed, the piece of skull is replaced and secured with
pieces of fine, soft wire. Finally, the surgeon sutures
the membrane, muscle, and skin of the scalp.

Preparation

I Craniotomy
Definition
Surgical removal of part of the skull to expose the
brain.

Purpose
A craniotomy is the most commonly performed
surgery for brain tumor removal. It may also be done
to remove a blood clot and control hemorrhage,
inspect the brain, perform a biopsy, or relieve pressure
inside the skull.

Precautions
Before the operation, the patient will have undergone diagnostic procedures such as computed tomography scans (CT) or magnetic resonance imaging
(MRI) scans to determine the underlying problem
that required the craniotomy and to get a better look
at the brain’s structure. Cerebral angiography may be
used to study the blood supply to the tumor, aneurysm, or other brain lesion.
1048

Before the surgery, patients are usually given
drugs to ease anxiety, and other medications to reduce
the risk of swelling, seizures, and infection after the
operation. Fluids may be restricted, and a diuretic may
be given before and during surgery if the patient has a
tendency to retain water. A catheter is inserted before
the patient goes to the operating room.
The scalp is shaved in the operating room right
before surgery; this is done so that any small nicks in
the skin will not have a chance to become infected
before the operation.

Aftercare
Oxygen, painkillers, and drugs to control swelling
and seizures are given after the operation. Codeine
may be given to relieve the headache that may occur
as a result of stretching or irritation of the nerves of the
scalp that happens during the craniotomy. Some type
of drainage from the head may be in place, depending
on the reason for the surgery.
Patients are usually out of bed within a day and
out of the hospital within a week. Headache and pain
from the scalp wound can be controlled with
medications.
GALE ENCYCLOPEDIA OF MEDICINE

Craniotomy

Bone is sawed
at base of flap

Scalp incisions

Cut joining
burr holes

Figure A

Figure B

A craniotomy is the most commonly performed surgery for brain tumor removal. There are two basic ways to open the skull: a
curving incision from behind the hairline in front of the ear and at the nape of the neck (figure A). To reach the brain, the surgeon
uses a hand drill to make holes in the skull, pushing a soft metal guide under the bone. The bone is sawed through until the bone
flap can be removed to expose the brain (figure B). (Illustration by Electronic Illustrators Group.)

KEY TERMS
Craniotome—A type of surgical drill used to operate on the skull. It has a self-controlled system that
stops the drill when the bone is penetrated.

The bandage on the skull should be changed regularly. Sutures closing the scalp will be removed, but soft
wires used to reattach the skull are permanent and require
no further attention. The patient should avoid getting the
scalp wet until all the sutures have been removed. A clean
cap or scarf can be worn until the hair grows back.

Risks
Accessing the area of the brain that needs repair
may damage other brain tissue. Therefore, the procedure carries with it some risk of brain damage that
could leave the patient with some loss of brain function. The surgeon performing the operation can give
the patient an assessment of the risk of his or her
particular procedure.
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
While every patient’s experience is different
depending on the reason for the surgery, age, and
overall health, if the surgery has been successful,
recovery is usually rapid because of the good supply
of blood to the area.

Abnormal results
Possible complications after craniotomy include:


swelling of the brain



excessive intracranial pressure



infection



seizures

Resources
BOOKS

Younson, Robert M., et al., editors. The Surgery Book: An
Illustrated Guide to 73 of the Most Common Operations.
New York: St. Martin’s Press, 1993.

Carol A. Turkington
1049

Creatine kinase test

I Creatine kinase test

KEY TERMS

Definition

Skeletal muscles—Muscles that move the skeleton.
All of the muscles under voluntary control are
skeletal muscles.
Smooth muscles—Muscles that surround the linings of the digestive system, airways, and circulatory system.

The creatine kinase test measures the blood levels
of certain muscle and brain enzyme proteins.

Purpose
Creatine kinase (CK or CPK) is an enzyme (a type
of protein) found in muscle and brain. Normally, very
little CK is found circulating in the blood. Elevated
levels indicate damage to either muscle or brain;
possibly from a myocardial infarction (heart attack),
muscle disease, or stroke.
There are three types, or isoforms, of CK:

CK levels are reduced in the first half of pregnancy,
and increased in the second half. CK levels are elevated in newborns.
The distribution of isoenzymes should be:

CK-I, or BB, is produced primarily by brain and
smooth muscle.



CK-I: 0%



CK-II, or MB, is produced primarily by heart muscle.



CK-II: 0–5%



CK-III, or MM, is produced primarily by skeletal
muscle.



CK-III: 95–100%.



Precautions
No special precautions are necessary, except in
patients with a bleeding disorder.

Description
A small amount of blood is drawn and used for
laboratory analysis.

Preparation
Physical activity may cause a rise in CK levels,
especially the CK-III fraction. Therefore, patients
should not engage in strenuous physical activity the
day of the test. The patient should report any recent
injections, falls, or bruises that have occurred, as these
may elevate CK levels as well.

Aftercare
No aftercare is required, except to keep the puncture site clean while it heals.

Risks
There are no risks to this test beyond the very
slight risk of infection at the puncture site.

Abnormal results
Elevation of CK-I may be seen in stroke, extreme
shock, or brain tumor.
Elevation of CK-II is seen after a myocardial infarction. It begins to rise three to six hours after the heart
attack, and may peak within 24 hours. It should then
return to normal. For this reason, it is a useful marker
for recent myocardial infarction, but not for one which
occurred more than a day before the test.
Elevation of CK-III indicates skeletal muscle
damage. This may occur from normal exercise,
trauma, or muscle disease. CK levels may be very
high early on in muscular dystrophy, but may fall to
normal later as muscle tissue is lost. Elevated CK is
also seen in myositis, myoglobinuria, toxoplasmosis,
and trichinosis. Hypothyroidism may also cause
elevated CK.
Resources
BOOKS

Corbett, Jane Vincent. Laboratory Tests and Diagnostic
Procedures with Nursing Diagnoses. 2nd ed. Los Altos,
CA: Appleton & Lange,1987.

Richard Robinson

Normal results
In females, total CK should be 10–79 units per
liter (U/L). In males, total CK should be 17–148 U/L.
1050

Creatine phosphokinase test see Creatine
kinase test
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Definition

Glomerulonephritis—Glomerulonephritis is an
inflammation of the filtering units of the kidney
(glomeruli). The condition hinders removal of
waste products, salt, and water from the bloodstream, leading to serious complications. It is the
most common cause of renal failure.

Creatine is an important compound produced by
the body. It combines with phosphorus to make a
high–energy phosphate compound in the body.
Creatine phosphate is used in skeletal muscle
contraction.

Pyelonephritis—Pyelonephritis is an inflammation
of the kidney itself, usually caused by a bacterial
infection. In its most serious form, complications
can include high blood pressure (hypertension) and
renal failure.

Purpose
The creatinine test is used to diagnose impaired
kidney function and to determine renal (kidney)
damage.

Precautions
A diet high in meat content can cause transient
elevations of serum creatinine. Some drugs that may
increase creatinine values include gentamicin, cimetidine, heavy-metal chemotherapeutic agents (e.g.,
cisplatin), and other drugs toxic to the kidneys, such
as the cephalosporins.

Preparation
The creatinine test requires a blood sample. It is
recommended that the patient be fasting (nothing to
eat or drink) for at least eight hours before the test.
The physician may also require that ascorbic acid
(vitamin C), barbiturates, and diuretics be withheld
for 24 hours.

Description

Risks

The creatinine test is used to measure the amount
of creatinine in the blood. Because creatinine is a
nonprotein end-product of creatine phosphate,
which is used in skeletal muscle contraction, the
daily production of creatine, and the following product, creatinine, depends on muscle mass, which fluctuates very little.

Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting
or feeling lightheaded after venipuncture, or hematoma (blood accumulating under the puncture site).

Creatinine is excreted entirely by the kidneys, and
therefore is directly related to renal function. When
the kidneys are functioning normally, the serum creatinine level should remain constant and normal. Slight
increases in creatine levels can appear after meals,
especially after ingestion of large quantities of meat,
and some diurnal variation may occur, with a low
point at 7 A.M. and a peak at 7 P.M. Serious renal
disorders, such as glomerulonephritis, pyelonephritis,
and urinary obstruction, will cause abnormal
elevations.

Normal values can vary from laboratory to
laboratory, but are generally in the following ranges:

The creatinine level is interpreted in conjunction
with another kidney function test called the Blood
Urea Nitrogen (BUN). The serum creatinine level
has much the same significance as the BUN but
tends to rise later. Because of this, determinations of
creatinine help to chronicle a disease process.
Generally, a doubling of creatinine suggests a 50%
reduction in kidney filtration rate.
GALE ENCYCLOPEDIA OF MEDICINE

Normal results



Adult female: 0.5–1.1 mg/dL



Adult male: 0.6–1.2 mg/dL



Adolescent: 0.5–1.0 mg/dL



Child: 0.3–0.7 mg/dL



Infant: 0.2–0.4 mg/dL



Newborn: 0.3–1.2 mg/dL.

Note that variations between sources for serum
creatinine normal ranges are greater than for other
important tests. For example, due to the greater
amount of muscle mass generally present, males normally demonstrate higher creatinine levels than
females. Also, because the kidney filtration rate normally increases in pregnancy, serum creatinine should
be slightly less during such periods. In older patients,
creatinine is reduced because of decreased muscle
1051

Creatinine test

I Creatinine test

Creutzfeldt-Jakob disease

mass. Similarly, other patients may have creatinine
levels in which muscle abnormalities must be taken
into consideration, such as long-term corticosteroid
therapy, high thyroid (hyperthyroidism), muscular
dystrophy, or paralysis.

dementia ending in death, usually within eight months
of symptom onset. It also is a very rare disease, affecting only about one in every million people throughout
the world. In the United States, CJD is thought to
affect about 250 people each year. CJD affects adults
primarily between ages 50 and 75.

Abnormal results
Two to 4 mg/dL indicate the presence of impairment of renal function. Greater than 4 mg/dL indicates serious impairment in renal function.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Creeping eruption see Cutaneous larva
migrans
CREST syndrome see Scleroderma
Cretinism see Hypothyroidism

I Creutzfeldt-Jakob disease
Definition
Creutzfeldt-Jakob disease (CJD) is a transmissible, rapidly progressing, neurodegenerative disorder
called a spongiform degeneration related to ‘‘mad
cow disease.’’

Spongiform encephalopathies
The most obvious pathologic feature of CJD is
the formation of numerous fluid-filled spaces in the
brain (vacuoles) resulting in a sponge-like appearance.
CJD is one of several human ‘‘spongiform encephalopathies,’’ diseases that produce this characteristic
change in brain tissue. Others are kuru; GerstmannStraussler-Scheinker disease, a genetic disorder predominantly characterized by cerebellar ataxia (a kind of
movement disorder); and fatal familial insomnia,
with symptoms of progressive sleeplessness, weakness,
and dysfunction of the nervous system that affects
voluntary and involuntary movements and functions.
Kuru was prevalent among the Fore people in
Papua, New Guinea, and spread from infected individuals after their deaths through the practice of ritual
cannibalism, in which the relatives of the dead person
honored him by consuming his organs, including the
brain. Discovery of the infectious nature of kuru won
the Nobel Prize for Carleton Gadjusek in 1976. The
incubation period for kuru was between four to 30
years or more. While kuru has virtually disappeared
since these cannibalistic practices stopped, several new
cases continue to arise each year.
Cases of CJD have been grouped into three types:
familial, iatrogenic, and sporadic.


Familial CJD, representing 5–15% of cases, is inherited in an autosomal dominant manner, meaning
that either parent may pass along the disease to a
child, who then may develop CJD later in life.



Iatrogenic CJD occurs when a person is infected
during a medical procedure, such as organ donation,
blood transfusion, or brain surgery. The rise in organ
donation has increased this route of transmission;
grafts of infected corneas and dura mater (the tissue
covering the brain) have been shown to transmit
CJD. Another source is hormones concentrated
from the pituitary glands of cadavers, some of
whom carried CJD, for use in people with growth
hormone deficiencies. Iatrogenic infection from
exposure to nerve-containing tissue represents a
small fraction of all cases. The incubation period
after exposure to the infectious agent is very long
and is estimated to be from less than 10 to more
than 30 years. It remains unlikely, but not

Description
Before 1995, Creutzfeldt-Jakob disease was not
well known outside the medical profession. Even
within it, many practitioners did not know much
about it. Most doctors had never seen a case. With
the recognition of a so-called ‘‘new variant’’ form of
CJD and the strong possibility that those with it
became infected simply by eating contaminated beef,
CJD has become one of the most talked-about
diseases in the world. Additionally, the radical theory
that the infectious agent is a normal protein that has
been changed in its form also has sparked much
interest.
First described in the early twentieth century
independently by Creutzfeldt and Jakob, CJD is a neurodegenerative disease causing a rapidly progressing
1052

GALE ENCYCLOPEDIA OF MEDICINE



Sporadic CJD represents at least 85% of all cases.
Sporadic cases have no identifiable source of infection. Death usually follows first symptoms within
eight months.
Animal forms and ‘‘mad cow disease’’

Six forms of spongiform encephalopathies are
known to occur in other mammals: scrapie in sheep,
recognized for more than 200 years; chronic wasting
disease in elk and mule deer in Wyoming and
Colorado; transmissible mink encephalopathy; exotic
ungulate encephalopathy in some types of zoo animals; feline spongiform encephalopathy in domestic
cats; and bovine spongiform encephalopathy (BSE) in
cows.
BSE was first recognized in Britain in 1986.
Besides the spongiform changes in the brain, BSE
causes dementia-like behavioral changes—hence the
name ‘‘mad cow disease.’’ BSE was thought to be an
altered form of scrapie, transmitted to cows when they
were fed sheep offal (slaughterhouse waste) as part of
their feed, but researchers believe it is a primary cattle
disease spread by contaminated feed.
The use of slaughterhouse offal in animal feed has
been common in many countries and has been practiced for at least 50 years. The trigger for the BSE
epidemic in Great Britain seems to have come in the
early 1980s, when the use of organic solvents for preparation of offal was altered there. It is possible that
these solvents had been destroying the agent called a
prion, thereby preventing infection, and that the
change in preparation procedure opened the way for
the agent to ‘‘jump species’’ and cause BSE in cows
that consumed scrapie-infected meal. The slaughter of
infected (but not yet visibly sick) cows at the end of
their useful farm lives, and the use of their carcasses
for feed, spread the infection rapidly and widely. For
at least a year after BSE was first recognized in British
herds, infected bovine remains continued to be incorporated into feed, spreading the disease still further.
Although milk from infected cows never has been
shown to pass the infectious agent, passage from
infected mother to calf may have occurred through
unknown means. Researchers also have tried to confirm how to stop infection of the human food chain
once the disease spread among cows. In 2003, a study
reported that it spread through nervous system tissue
in processed meat and that proper temperature and
pressure controls could help ensure safety of commercial beef.
GALE ENCYCLOPEDIA OF MEDICINE

Beginning in 1988, the British government took
steps to stop the spread of BSE, banning the use of
bovine offal in feed and other products and ordering
the slaughter of infected cows. By then, the slowacting agent had become epidemic in British herds.
In 1992, it was diagnosed in more than 25,000 animals
(1% of the British herd). By mid-1997, the cumulative
number of BSE cases in the United Kingdom had risen
to more than 170,000. The feeding ban stemmed the
tide of the epidemic; however, the number of new cases
each week fell from a peak of 1,000 in 1993 to less than
300 two years later.
The export of British feed and beef to member
countries was banned by the European Union, but
cases of BSE had developed in Europe by then as
well; however, by mid-1997, only about 1,000 cases
had been identified. In 1989, the United States banned
import of British beef and began monitoring United
States herds in 1990. In December 2003, the first and
only case (as of late March 2004) of BSE was discovered in the United States. This prompted recommendations of new safeguards to prevent further spread.
Among these were regulations banning animal blood
in cattle feed.
Variant CJD: The human equivalent of mad cow
disease
From the beginning of the BSE epidemic, scientists and others in Britain feared that BSE might jump
species again to infect humans who had consumed
infected beef. This, however, had never occurred in
scrapie from sheep, a disease known for hundreds of
years. In 1996, the first report of this possibility
occurred and the fear seemed to be realized with the
first cases of a new variant of Creutzfeldt-Jacob disease, termed nvCJD, now just vCJD. Its victims are
much younger than the 60–65 year old average for
CJD, and the time from symptom onset to death has
averaged 12 months or more instead of eight. The
disease appears to cause more psychiatric symptoms
early on. EEG abnormalities characteristic of CJD are
not typically seen in vCJD.
By early 2004, CJD had claimed 143 victims in
Great Britain and 10 in other countries. It is of major
concern that the number of cases per year seems to be
increasing by a factor of 1.35 each year. The only
known case in the United States to date had been
acquired while the person had been in Great Britain.
Evidence is growing stronger that vCJD is in fact
caused by BSE:


almost all of the cases so far have occurred in Great
Britain, the location of the BSE epidemic
1053

Creutzfeldt-Jakob disease

impossible, that blood from patients with CJD is
infectious to others by transfusion.

Creutzfeldt-Jakob disease



BSE injected into monkeys produces a disease very
similar to vCJD



BSE and vCJD produce the same brain lesions after
the same incubation period when injected into
laboratory mice



brain proteins isolated from vCJD victims, but not
from the other forms of CJD, share similar molecular
characteristics with brain proteins of animals that
died from BSE

Researchers now treat the BSE-vCJD connection
as solidly established.
Assuming that BSE is the source, the question that
has loomed from the beginning has been how many
people will eventually be affected. Epidemiological
models once placed estimates at tens of thousands,
but in 2003, scientists predicted a quicker end to the
epidemic and have substantially lowered the numbers
expected to contract the disease. The exact incubation
period of vCJD in humans is about 10 to 20 years or
longer, so it is more difficult to predict the number of
cases. Researchers know that some people are more
susceptible to vCJD, including young people age 10 to
20 years old.

Causes and symptoms
Causes
It is clear that Creutzfeldt-Jakob disease is caused
by an infectious agent, but it is not yet clear what type
of agent that is. Originally assumed to be a virus,
evidence is accumulating that, instead, CJD is caused
by a protein called a prion (PREE-on, for ‘‘proteinaceous infectious particle’’) transmitted from victim to
victim. The other spongiform encephalopathies also
are hypothesized to be due to prion infection.
If this hypothesis is proven true, it would represent one of the most radical new ideas in biology since
the discovery of deoxyribonucleic acid (DNA). All
infectious diseases, in fact all life, use nucleic acids—
DNA or ribonucleic acid (RNA)—to code the instructions needed for reproduction. Inactivation of the
nucleic acids destroys the capacity to reproduce.
However, when these same measures are applied to
infected tissue from spongiform encephalopathy victims, infectivity is not destroyed. Furthermore, purification of infected tissue to concentrate the infectious
fraction yields protein, not nucleic acid. While it
remains possible that some highly stable nucleic acid
remains hidden within the purified protein, this is seemingly less and less likely as further experiments are
done. The ‘‘prion hypothesis,’’ as it is called, is now
widely accepted, at least provisionally, by most
1054

researchers in the field. The most vocal proponent of
the hypothesis, Stanley Prusiner, was awarded the
Nobel Prize in 1997 for his work in the prion diseases.
A prion is an altered form of a normal brain
protein. The normal protein has a helical shape along
part of its length. In the prion form, a sheet structure
replaces the helix. According to the hypothesis, when
the normal form interacts with the prion form, some of
its helical part is converted to a sheet, thus creating a
new prion capable of transforming other normal
forms. In this way, the disease process resembles crystallization more than typical viral infection, in which
the virus commands the host’s cellular machinery to
reproduce more of the virus. Build-up of the sheet
form causes accumulation of abnormal protein
clumps and degeneration of brain cells, which is
thought to cause the disease.
The brain protein affected by the prion, called
PrP, is part of the membrane of brain cells, but its
exact function is unknown. Exposure to the infectious
agent is, of course, still required for disease development. Prion diseases are not contagious in the usual
sense, and transmission from an infected person to
another person requires direct inoculation of infectious material.
Familial CJD, on the other hand, does not require
exposure, but develops through the inheritance of
other, more disruptive mutations in the gene for the
normal PrP protein. The other two inherited human
prion diseases, Gerstmann-Straussler-Scheinker disease and fatal familial insomnia, involve different
mutations in the same gene.
The large majority of CJD cases are sporadic,
meaning they have no known route of infection or
genetic link. Causes of sporadic CJD are likely to be
diverse and may include spontaneous genetic mutation, spontaneous protein changes, or unrecognized
exposure to infectious agents. It is highly likely that
future research will identify more risk factors associated with sporadic CJD.
Symptoms
About one in four people with CJD begin their
illness with weakness, changes in sleep patterns,
weight loss, or loss of appetite or sexual drive. A
person with CJD may first complain of visual disturbances, including double vision, blurry vision, or partial loss of vision. Some visual symptoms are
secondary to cortical blindness related to death of
nerve cells in the occipital lobe of the brain responsible
for vision. This form of visual loss is unusual in that
patients may be unaware that they are unable to see.
GALE ENCYCLOPEDIA OF MEDICINE

The most characteristic symptom of CJD is
rapidly progressing dementia, or loss of mental function. Dementia is marked by:


memory losses



impaired abstraction and planning



language and comprehension disturbances



poor judgment



disorientation



decreased attention and increased restlessness



personality changes and psychosis



hallucinations

Muscle spasms and jerking movements, called
myoclonus, are also a prominent symptom of CJD.
Balance and coordination disturbance (ataxia), is
common in CJD, and is more pronounced in nvCJD.
Stiffness, difficulty moving, and other features representing Parkinson’s disease are seen and can progress
to akinetic mutism, which is a state of being unable to
speak or move.

Diagnosis
CJD is diagnosed by a clinical neurological exam
and electroencephalography (EEG), which shows
characteristic spikes called triphasic sharp waves.
Magnetic resonance imaging (MRI) or computed
tomography scans (CT) should be done to exclude
other forms of dementia, and in CJD typically shows
atrophy or loss of brain tissue. Lumbar puncture, or
spinal tap, may be done to rule out other causes of
dementia (as cell count, chemical analysis, and other
routine tests are normal in CJD) and to identify elevated levels of marker proteins known as 14-3-3.
Another marker, neuron-specific enolase, may also
be increased in CJD. CJD is conclusively diagnosed
after death by brain autopsy. Scientists are investigating whether testing lymphatic tissue such as the tonsil
may be an early tool in vCJD diagnosis. Additionally,
recent studies have suggested that other blood tests
may be useful as well.

Treatment
There is no cure for CJD, and no treatment that
slows the progression of the disease. Drug therapy and
nursing care are aimed at minimizing psychiatric symptoms and increasing patient comfort. However, the
rapid progression of CJD frustrates most attempts at
treatment, since decreasing cognitive function and
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Autosomal dominant inheritance—A pattern of
inheritance in which a trait will be expressed if
the gene is inherited from either parent.
Encephalopathy—Brain disorder characterized by
memory impairment and other symptoms.
Iatrogenic—Caused by a medical procedure.
Nucleic acids—The cellular molecules DNA and
RNA that act as coded instructions for the production of proteins and are copied for transmission of
inherited traits.

more prominent behavioral symptoms develop so
quickly. Despite the generally grim prognosis, a few
CJD patients progress more slowly and live longer
than the average; for these patients, treatment will be
more satisfactory. Scientists are investigating whether
some medicines that can ‘‘break’’ the abnormal protein
form may be useful and whether a vaccine could help.

Prognosis
Creutzfeldt-Jakob disease has proven invariably
fatal, with death following symptom onset by an average of eight months. About 5% of patients live longer
than two years. Death from vCJD has averaged
approximately 12 months after onset. However, in
2003, clinicians reported improvement in a patient
with vCJD who received a new experimental drug
called Pentosan.

Prevention
There is no known way to prevent sporadic CJD, by
far the most common type. Not everyone who inherits
the gene mutation for familial CJD will develop the
disease, but at present, there is no known way to predict
who will and who will not succumb. The incidence of
iatrogenic CJD has fallen with recognition of its sources,
the development of better screening techniques for
infected tissue, and the use of sterilization techniques
for surgical instruments that inactivate prion proteins.
Fortunately, scientists are making progress. In 2003,
researchers announced that they had uncovered the
basis for diagnosing, treating and possibly preventing
prion diseases such as vCJD. Their research possibly
could lead to a vaccine and immunotherapy drugs.
Strategies for prevention of vCJD are a controversial matter, as they involve a significant sector of
1055

Creutzfeldt-Jakob disease

These symptoms may appear weeks to months before
the onset of dementia.

Cri du chat syndrome

the agricultural industry and a central feature of the
diet in many countries. The infectious potential of
contaminated meat is unknown, because the ability
to detect prions within meat is limited. Surveillance
of North American herds strongly suggests there is no
BSE here, and strict regulations on imports of
European livestock make future outbreaks highly
unlikely. Therefore, avoidance of all meat originating
in North America, simply on grounds of BSE risk, is a
personal choice unsupported by current data.
Resources
PERIODICALS

Brown, Paul, et al. ‘‘Ultra-high Pressure Inactivation of
Prion Infectivity in Processed Meat: A Practical
Method to Prevent Human Infection.’’ Proceedings of
the National Academy of Sciences of the United States
May 13, 2003: 6093-6095.
‘‘GP Sees Patient with vCJD Improve.’’ Pulse June 23,
2003: 12.
Kaye, Donald. ‘‘FDA Launches New Mad Cow Rules to
Protect U.S. Food, Feed.’’ Clinical Infectious Diseases
March 15, 2004: 3–5.
‘‘Large Human Mad Cow Epidemic Unlikely— Scientists.’’
Clinical Infectious Diseases April 15, 2003: i.
‘‘Report Appears to Confirm Blood-borne Transmission of
Creutzfeldt-Jakob Disease.’’ Blood Weekly January 8,
2004: 28.
‘‘Researchers Discover Possible Diagnosis, Treatment,
Vaccine.’’ Immunotherapy Weekly June 25, 2003: 2.
‘‘Scientists Predict Swift End to vCJD Epidemic.’’ British
Medical Journal May 24, 2003: 1104 -1111.
‘‘U.S. Lawmakers Want Increase in Mad Cow Testing.’’
Healthcare Purchasing News March 2004: 85.

Larry I. Lutwick, MD
Teresa G. Odle

I Cri du chat syndrome
Definition
Cri du chat syndrome occurs when a piece of
chromosomal material is missing from a particular
region on chromosome 5. The disorder is also called
cat cry syndrome or chromosome deletion 5p syndrome. Individuals with this syndrome have unusual
facial features, poor muscle tone (hypotonia), small
head size (microcephaly), and mental retardation. A
classic feature of the syndrome is the cat-like cry
made by infants with this disorder.
1056

Description
Dr. Jerome Lejeune first described cri du chat
syndrome in 1963. The syndrome is named for the
cat-like cry made by infants with this genetic disorder.
Cri du chat means ‘‘cat’s cry’’ in French. This unusual
cry is caused by abnormal development of the larynx
(organ in the throat responsible for voice production).
Cri du chat syndrome is also called 5p deletion
syndrome because it is caused by a deletion, or
removal, of genetic material from chromosome 5.
The deletion that causes cri du chat syndrome occurs
on the short or ‘‘p’’ arm of chromosome 5. This
deleted genetic material is vital for normal development. Absence of this material results in the features
associated with cri du chat syndrome.
A high-pitched mewing cry during infancy is a
classic feature of cri du chat. Infants with cri du chat
also typically have low birth weight, slow growth, a
small head (microcephaly) and poor muscle tone
(hypotonia). Infants with cri du chat may have congenital heart defects. Individuals with cri du chat syndrome have language difficulties, delayed motor skill
development, and mental retardation. Behavioral
problems may also develop as the child matures.
It has been estimated that cri du chat syndrome
occurs in one of every 50,000 live births. It accounts
for 1 in every 500 cases of mental retardation.
According to the 5p minus Society, approximately
50–60 children are born with cri du chat syndrome in
the United States each year. It can occur in all races
and in both sexes, although there is a slight female
predominance. The male:female ratio is 3:4.

Causes and symptoms
Cri du chat is the result of a chromosome
abnormality—a deleted piece of chromosomal material on chromosome 5. In about 80% of patients,
the defective chromosome comes from the father.
In 90% of patients with cri du chat syndrome, the
deletion is sporadic. This means that it happens
randomly and is not hereditary. If a child has cri du
chat due to a sporadic deletion, the chance the
parents could have another child with cri du chat is
1%. In approximately 10% of patients with cri du
chat, there is a hereditary chromosomal rearrangement that causes the deletion. If a parent has this
rearrangement, the risk for them to have a child with
cri du chat is greater than 1%.
The severity of mental retardation in cri du chat
syndrome is correlated with the extent of deletion of
delta-catenin, a protein with an important role in
GALE ENCYCLOPEDIA OF MEDICINE

An abnormal larynx causes the unusual cat-like
cry made by infants that is a hallmark of the syndrome. As children with cri du chat get older, the
cat-like cry becomes less noticeable. This feature can
make the diagnosis more difficult in older patients. In
addition to the cat-like cry, individuals with cri du chat
also have unusual facial features. These facial differences can be very subtle or more obvious.
Microcephaly (small head size) is common. During
infancy many patients with cri du chat do not gain
weight or grow normally. Approximately 30% of
infants with cri du chat have a congenital heart defect.
Hypotonia (poor muscle tone) is also common, leading to problems with eating and slow, but normal
development. Mental retardation is present in all
patients with cri du chat, but the degree of mental
retardation varies among patients.

Diagnosis
During infancy, the diagnosis of cri du chat syndrome is strongly suspected if the characteristic catlike cry is heard. If a child has this unusual cry or other
features seen in cri du chat syndrome, chromosome
testing should be performed. Chromosome analysis
provides the definitive diagnosis of cri du chat
syndrome and can be performed from a blood
test. Chromosome analysis, also called karyotyping,
involves staining the chromosomes and examining
them under a microscope. In some cases the deletion
of material from chromosome 5 can be easily seen. In
other cases, further testing must be performed. FISH
(fluorescence in-situ hybridization) is a special technique that detects very small deletions. The majority of
the deletions that cause cri du chat syndrome can be
identified using the FISH technique.
Cri du chat syndrome can be detected before birth
if the mother undergoes amniocentesis testing or chorionic villus sampling (CVS). This testing would only
be recommended if the mother or father is known to
have a chromosome rearrangement, or if they already
have a child with cri du chat syndrome.

Treatment
As of 2004 there is no cure for cri du chat syndrome. Treatment consists of supportive care and
developmental therapy. Behavioral modification therapy has been found to be useful to control head-banging, hyperactivity, and other behavioral problems that
emerge during later childhood.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Amniocentesis—A procedure performed at 16–18
weeks of pregnancy in which a needle is inserted
through a woman’s abdomen into her uterus to
draw out a small sample of the amniotic fluid
from around the baby. Either the fluid itself or
cells from the fluid can be used for a variety of
tests to obtain information about genetic disorders
and other medical conditions in the fetus.
Centromere—The centromere is the constricted
region of a chromosome. It performs certain functions during cell division.
Chorionic villus sampling (CVS)—A procedure
used for prenatal diagnosis at 10–12 weeks gestation. Under ultrasound guidance a needle is
inserted either through the mother’s vagina or
abdominal wall and a sample of cells is collected
from around the early embryo. These cells are then
tested for chromosome abnormalities or other
genetic diseases.
Chromosome—A microscopic thread-like structure found within each cell of the body and consists
of a complex of proteins and DNA. Humans have
46 chromosomes arranged into 23 pairs. Changes
in either the total number of chromosomes or their
shape and size (structure) may lead to physical or
mental abnormalities.
Congenital—Refers to a disorder that is present at
birth.
Deletion—The absence of genetic material that
is normally found in a chromosome. Often,
the genetic material is missing due to an error in
replication of an egg or sperm cell.
Hypotonia—Reduced or diminished muscle tone.
Karyotyping—A laboratory procedure in which
chromosomes are separated from cells, stained
and arranged so that their structure can be studied
under the microscope.
Microcephaly—An abnormally small head.

Prognosis
Individuals with cri du chat have a 10% mortality
during infancy due to complications associated with
congenital heart defects, hypotonia, and feeding difficulties. Once these problems are controlled, most individuals with cri du chat syndrome have a normal
lifespan. The degree of mental retardation can be
1057

Cri du chat syndrome

brain functioning. The more extensive the deletion, the
more profound the mental dysfunction.

Crohn’s disease

severe. However, a recent study suggested that the
severity is somewhat affected by the amount of therapy received.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Chromosomal Abnormalities.’’ Section 19, Chapter
261 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Developmental Problems.’’ Section 19, Chapter 262 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Chen, Harold, MD. ‘‘Cri-du-chat Syndrome.’’ eMedicine
November 21, 2002. <http://emedicine.com/ped/
topic504.htm>.
Israely, I., R. M. Costa, C. W. Xie, et al. ‘‘Deletion
of the Neuron-Specific Protein Delta-Catenin
Leads to Severe Cognitive and Synaptic
Dysfunction.’’ Current Biology 14
(September 21, 2004): 1657–1663.
Van Buggenhout, G. J. C. M., et al. ‘‘Cri du Chat
Syndrome: Changing Phenotype in Older Patients.’’
American Journal of Medical Genetics 90 (2000):
203–215.

I Crohn’s disease
Definition
Crohn’s disease is a type of inflammatory bowel
disease (IBD), resulting in swelling and dysfunction of
the intestinal tract.

Description
Crohn’s disease involves inflammation of the
intestine, especially the small intestine. Inflammation
refers to swelling, redness, and loss of normal function. There is evidence that the inflammation is caused
by various products of the immune system that attack
the body itself instead of helpfully attacking a foreign
invader (a virus or bacteria, for example). The inflammation of Crohn’s disease most commonly affects the
last part of the ileum (a section of the small intestine),
and often includes the large intestine (the colon).
However, inflammation may also occur in other
areas of the gastrointestinal tract, affecting the
mouth, esophagus, or stomach. Crohn’s disease differs
from ulcerative colitis, the other major type of IBD, in
two important ways:


The inflammation of Crohn’s disease may be discontinuous, meaning that areas of involvement in the
intestine may be separated by normal, unaffected
segments of intestine. The affected areas are called
‘‘regional enteritis,’’ while the normal areas are called
‘‘skip areas.’’



The inflammation of Crohn’s disease affects all the
layers of the intestinal wall, while ulcerative colitis
affects only the lining of the intestine.

ORGANIZATIONS

5p- Society. 7108 Katella Ave. #502, Stanton, CA 90680.
(888) 970-0777. <http://www.fivepminus.org>.
Alliance of Genetic Support Groups. 4301 Connecticut Ave.
NW, Suite 404, Washington, DC 20008. (202) 966-5557.
Fax: (202) 966-8553. <http://
www.geneticalliance.org>.
Cri du Chat Society. Dept. of Human Genetics, Box 33,
MCV Station, Richmond VA 23298. (804) 786-9632.
Cri du Chat Syndrome Support Group. <http://
www.cridchat.u-net.com>.
National Organization for Rare Disorders (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT
06813-1968. (203) 744-0100. Fax: (203) 798-2291.
<http://www.rarediseases.org>.
OTHER

OMIM—Online Mendelian Inheritance in Man. <http://
www.ncbi.nlm.nih.gov/Omim/>.

Holly Ann Ishmael, M.S.
Rebecca J. Frey, PhD

Crib death see Sudden infant death
syndrome
1058

Also, ulcerative colitis does not usually involve the
small intestine; in rare cases, it involves the terminal
ileum (so-called ‘‘backwash’’ ileitis).
In addition to inflammation, Crohn’s disease
causes ulcerations, or irritated pits in the intestinal
wall. These pits occur because the inflammation has
made areas of tissue shed.
Crohn’s disease may be diagnosed at any age,
although most diagnoses are made between the ages
15 to 35. About 0.02–0.04% of the population suffers
from this disorder, with men and women having an
equal chance of being stricken. Whites are more frequently affected than other racial groups, and people
of Jewish origin are between three and six times more
likely to suffer from IBD. IBD runs in families; an IBD
patient has a 20% chance of having other relatives
who are fellow sufferers.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The cause of Crohn’s disease is unknown. No
infectious agent (virus, bacteria, or fungi) has been
identified as the cause of Crohn’s disease. Still, some
researchers have theorized that some type of infection
may have originally been responsible for triggering the
immune system, resulting in the continuing and outof-control cycle of inflammation that occurs in
Crohn’s disease. Other evidence for a disorder of the
immune system includes the high incidence of other
immune disorders that may occur along with Crohn’s
disease.
The first symptoms of Crohn’s disease include
diarrhea, fever, abdominal pain, inability to eat,
weight loss, and fatigue. Some patients have severe
pain that mimics appendicitis. It is rare, however, for
patients to notice blood in their bowel movements.
Because Crohn’s disease severely limits the ability of
the affected intestine to absorb the nutrients from
food, a patient with Crohn’s disease can have signs
of malnutrition, depending on the amount of intestine
affected and the duration of the disease.
The combination of severe inflammation, ulceration, and scarring that occurs in Crohn’s disease can
result in serious complications, including obstruction,
abscess formation, and fistula formation.
An obstruction is a blockage in the intestine. This
obstruction prevents the intestinal contents from passing beyond the point of the blockage. The intestinal
contents ‘‘back up,’’ resulting in constipation, vomiting, and intense pain. Although rare in Crohn’s disease (because of the increased thickness of the
intestinal wall due to swelling and scarring), a severe
bowel obstruction can result in an intestinal wall
perforation (a hole in the intestine). Such a hole in
the intestinal wall would allow the intestinal
contents, usually containing bacteria, to enter the
abdomen. This complication could result in a severe,
life-threatening infection.
Abcess formation is the development of a walledoff pocket of infection. A patient with an abscess will
have bouts of fever, increased abdominal pain, and
may have a lump or mass that can be felt through the
wall of the abdomen.
Fistula formation is the formation of abnormal
channels. These channels may connect one area of the
intestine to another neighboring section of intestine.
GALE ENCYCLOPEDIA OF MEDICINE

Fistulas may join an area of the intestine to the vagina
or bladder, or they may drain an area of the intestine
through the skin. Abscesses and fistulas commonly
affect the area around the anus and rectum (the very
last portions of the colon allowing waste to leave the
body). These abnormal connections allow the bacteria
that normally live in the intestine to enter other areas
of the body, causing potentially serious infections.
Patients suffering from Crohn’s disease also have
a significant chance of experiencing other disorders.
Some of these may relate specifically to the intestinal
disease, and others appear to have some relationship
to the imbalanced immune system. The faulty absorption state of the bowel can result in gallstones and
kidney stones. Inflamed areas in the abdomen may
press on the tube that drains urine from the kidney
to the bladder (the ureter). Ureter compression can
make urine back up into the kidney, enlarge the ureter
and kidney, and can potentially lead to kidney
damage. Patients with Crohn’s disease also frequently
suffer from:


arthritis (inflammation of the joints)



spondylitis (inflammation of the vertebrae, the bones
of the spine)



ulcers of the mouth and skin



painful, red bumps on the skin



inflammation of several eye areas



inflammation of the liver, gallbladder, and/or the
channels (ducts) that carry bile between and within
the liver, gallbladder, and intestine

The chance of developing cancer of the intestine is
greater than normal among patients with Crohn’s disease, although this chance is not as high as among
those patients with ulcerative colitis.

Diagnosis
Diagnosis is first suspected based on a patient’s
symptoms. Blood tests may reveal an increase in
certain types of white blood cells, an indication that
some type of inflammation is occurring in the body.
The blood tests may also reveal anemia and other signs
of malnutrition due to malabsorption (low blood protein; variations in the amount of calcium, potassium,
and magnesium present in the blood; changes in
certain markers of liver function). Stool samples may
be examined to make sure that no infectious agent is
causing the diarrhea, and to see if the waste contains
blood.
During an endoscopic exam, a doctor passes a
flexible tube with a tiny, fiber-optic camera device
1059

Crohn’s disease

Crohn’s disease is a chronic disorder. While the
symptoms can be improved, a patient will not be completely cured of the underlying disease.

Crohn’s disease

every effort to distinguish between these two diseases.
Because the long-term complications of the diseases
are different, treatment will depend on careful diagnosis of the specific IBD present.

Treatment
Treatments for Crohn’s disease try to reduce the
underlying inflammation, the resulting malabsorption/malnutrition, the uncomfortable symptoms of
crampy abdominal pain and diarrhea, and the possible
complications (obstructions, abscesses, and fistulas).

A barium x-ray showing the colon of a patient with Crohn’s
disease where the large and small intestines join (bottom
left). (Custom Medical Stock Photo. Reproduced by permission.)

through the rectum and into the colon. The doctor can
then carefully examine the lining of the intestine for
signs of inflammation and ulceration that might
suggest Crohn’s disease. A tiny sample (a biopsy) of
the intestine can also be taken through the endoscope,
and the tissue will be examined under a microscope for
evidence of Crohn’s disease.
X rays can be helpful for diagnosis, and also for
determining how much of the intestine is involved in
the disease. For these x rays, the patient must either
drink a chalky solution containing barium, or receive a
barium enema (a solution that is administered through
the rectum). Barium helps to ‘‘light up’’ the intestine,
allowing more detail to be seen on the resulting x rays.
While Crohn’s disease and ulcerative colitis are
similar, they are also very different. Although it can
be difficult to determine whether a patient has Crohn’s
disease or ulcerative colitis, it is important to make
1060

Inflammation can be treated with a drug called
sulfasalazine. Sulfasalazine is made up of two parts.
One part is related to the sulfa antibiotics; the other
part is a form of the anti-inflammatory chemical,
salicylic acid (related to aspirin). Sulfasalazine is not
well absorbed from the intestine, so it stays mostly
within the intestine, where it is broken down into its
components. It is believed that the salicylic acid component actively treats Crohn’s disease by fighting
inflammation. Some patients do not respond to sulfasalazine, and require steroid medications (such as
prednisone). Steroids, however, must be used carefully to avoid the complications of these drugs,
including increased risk of infection and weakening
of bones (osteoporosis). Some very potent immunosuppressive drugs, which interfere with the products
of the immune system and can hopefully decrease
inflammation, may be used for those patients who
do not improve on steroids.
A new drug called infliximab (Remicade) appears
to be a powerful treatment for Crohn’s disease, particularly for patients who have not responded well to other
forms of treatment. Infliximab is administered through
infusion, and consists of a monoclonal antibody that
interferes with the inflammatory process mediated by
tumor necrosis factor-alpha (TNF-a). Patients taking
infliximab seem to be able to decrease their use of steroid
medications, and require fewer surgical interventions.
Furthermore, infliximab is the first medication
approved for treating fistulas. Unfortunately, infliximab can only be used on a short-term basis, because
its interference with TNF-a activity can also predispose
patients to serious infection. More research is needed to
try to harness the benefits of infliximab, while avoiding
the potential complications.
Serious cases of malabsorption/malnutrition may
need to be treated by providing nutritional supplements. These supplements must be in a form that can
be absorbed from the damaged, inflamed intestine.
Some patients find that certain foods are hard to
digest, including milk, large quantities of fiber, and
GALE ENCYCLOPEDIA OF MEDICINE

Abscess—A walled-off pocket of pus caused by
infection.
Endoscope—A medical instrument that can be
passed into an area of the body (the bladder or intestine, for example) to allow examination of that area.
The endoscope usually has a fiber-optic camera that
allows a greatly magnified image to be shown on a
television screen viewed by the operator. Many
endoscopes also allow the operator to retrieve a
small sample (biopsy) of the area being examined,
to more closely view the tissue under a microscope.
Fistule—An abnormal channel that creates an open
passageway between two structures that do not
normally connect.
Gastrointestinal tract—The entire length of the
digestive system, running from the stomach,
through the small intestine, large intestine, and
out the rectum and anus.
Immune system—The body system responsible for
producing various cells and chemicals that fight
infection by viruses, bacteria, fungi, and other foreign invaders. In autoimmune disease, these cells
and chemicals turn against the body itself.
Inflammation—The result of the body’s attempts to
fight off and wall off an area that is infected.
Inflammation results in the classic signs of redness,
heat, swelling, and loss of function.
Obstruction—A blockage.
Ulceration—A pitted area or break in the continuity of a surface such as skin or mucous membrane.

spicy foods. When patients are suffering from an
obstruction, or during periods of time when symptoms
of the disease are at their worst, they may need to
drink specially formulated, high-calorie liquid supplements. Those patients who are severely ill may need to
receive their nutrition through a needle inserted in a
vein (intravenously), or even by a tiny tube (a catheter)
inserted directly into a major vein in the chest.
A number of medications are available to help
decrease the cramping and pain associated with
Crohn’s disease. These include loperamide, tincture
of opium, and codeine. Some fiber preparations
(methylcellulose or psyllium) may be helpful, although
some patients do not tolerate them well.
The first step in treating an obstruction involves
general attempts to decrease inflammation with
GALE ENCYCLOPEDIA OF MEDICINE

sulfasalazine, steroids, or immunosuppressive drugs.
A patient with a severe obstruction will have to stop
taking all food and drink by mouth, allowing the bowel
to ‘‘rest.’’ Abscesses and other infections will require
antibiotics. Surgery may be required to repair an
obstruction that does not resolve on its own, to remove
an abscess, or to repair a fistula. Such surgery may
involve the removal of a section of the intestine. In
extremely severe cases of Crohn’s disease that do not
respond to treatment, a patient may need to have the
entire large intestine removed (an operation called a
colectomy). In this case, a piece of the remaining small
intestine is pulled through an opening in the abdomen.
This bit of intestine is fashioned surgically to allow a
special bag to be placed over it. This bag catches the
body’s waste, which no longer can be passed through
the large intestine and out of the anus. This opening, which will remain in place for life, is called an
ileostomy.

Prognosis
Crohn’s disease is a life-long illness. The severity
of the disease can vary, and a patient can experience
periods of time when the disease is not active and he or
she is symptom free. However, the complications and
risks of Crohn’s disease tend to increase over time.
Well over 60% of all patients with Crohn’s disease
will require surgery, and about half of these patients
will require more than one operation over time. About
5–10% of all Crohn’s patients will die of their disease,
primarily due to massive infection.

Rosalyn Carson-DeWitt, MD

Cromolyn see Antiasthmatic drugs
Cross-eye see Strabismus
Cross-gender identification see Gender
identity disorder

I Croup
Definition
Croup is a common childhood ailment. Typically,
it arises from a viral infection of the larynx (voice box)
and is associated with mild upper respiratory symptoms such as a runny nose and cough. The key symptom is a harsh barking cough. Croup is usually not
1061

Croup

KEY TERMS

Croup

serious and most children recover within a few days. In
a small percentage of cases, a child develops breathing
difficulties and may need medical attention.

more); seems unalert or confused; or has pale or
blue-tinged skin.

Diagnosis
Description
At one time, the term croup was primarily associated with diphtheria, a life-threatening respiratory
infection. Owing to widespread vaccinations,
diphtheria has become rare in the United States, and
croup currently refers to a mild viral infection of the
larynx. Croup is also known as laryngotracheitis, a
medical term that describes the inflammation of the
trachea (windpipe) and larynx.
Parainfluenza viruses are the typical root cause of
the infection, but influenza (flu) and cold viruses may
sometimes be responsible. All of these viruses are highly
contagious and easily transmitted between individuals
via sneezing and coughing. Children between the ages of
three months and six years are usually affected, with the
greatest incidence at one to two years of age. Croup can
occur at any time of the year, but it is most typical
during early autumn and winter. The characteristic
harsh barking of a croupy cough can be very distressing,
but it rarely indicates a serious problem. Most children
with croup can be treated very effectively at home;
however, 1–5% may require medical treatment.
Croup may sometimes be confused with more
serious conditions, such as epiglottitis or bacterial tracheitis. These ailments arise from bacterial infection
and must receive medical treatment.

Causes and symptoms
The larynx and trachea may become inflamed or
swollen from an upper respiratory viral infection. The
hallmark sign of croup is a harsh, barking cough. This
cough may be preceded by one to three days of symptoms that resemble a slight cold. A croupy cough is
often accompanied by a runny nose, hoarseness, and a
low fever. When the child inhales, there may be a raspy
or high-pitched noise, called stridor, owing to the narrowed airway and accumulated mucus. In the presence
of stridor, medical attention is required.
However, the airway rarely narrows so much that
breathing is impeded. Symptoms usually go away
completely within a few days. Medical treatment may
be sought if the child’s symptoms do not respond to
home treatment.
Emergency medical treatment is required immediately if the child has difficulty breathing, swallowing,
or talking; develops a high fever (103  F/39.4  C or
1062

Croup is diagnosed based on the symptoms. If
symptoms are particularly severe, or do not respond
to treatment, an x ray of the throat area is done to
assess the possibility of epiglottitis or other blockage
of the airway.

Treatment
Home treatment is the usual method of managing
croup symptoms. It is important that the child is kept
comfortable and calm to the best degree possible,
because crying can make symptoms seem worse.
Humid air can help a child with croup feel more comfortable. Recommended methods include sitting in a
steamy bathroom with the hot water running or using
a cool-water vaporizer or humidifier. However,
research in 2004 found that although cool-mist
therapy at home or in the hospital may add to the
child’s comfort, it does little to treat the actual
condition. The child should drink frequently in order
to stay well hydrated. To treat any fever, the child may
be given an appropriate dose of acetaminophen (like
Tylenol). Antihistamines and decongestants are ineffective in treating croup. All children under the age of 18
should not be given aspirin, as it may cause Reye’s
syndrome, a life-threatening disease of the brain.
If the child does not respond to home treatment,
medical treatment at a doctor’s office or an emergency
room could be necessary. Based on the severity of
symptoms and the response to treatment, the child
may need to be admitted to a hospital.
For immediate symptom relief, epinephrine may be
administered as an inhaled aerosol. Effects last for up to
two hours, but there is a possibility that symptoms
may return. For that reason, the child is kept under
supervision for three or more hours. Steroids (corticosteroids) such as prednisone may be used to treat croup,
particularly if the child has stridor when resting.
Of the 1–5% of children requiring medical treatment, approximately 1% need respiratory support.
Such support involves intubation (inserting a tube
into the trachea) and oxygen administration.

Alternative treatment
Botanical/herbal medicines can be helpful in healing the cough that is commonly associated with croup.
Several herbs to consider for cough treatment include
aniseed (Pimpinella anisum), sundew (Drosera
GALE ENCYCLOPEDIA OF MEDICINE

Diphtheria—A serious, frequently fatal, bacterial
infection that affects the respiratory tract.
Vaccinations given in childhood have made
diphtheria very rare in the United States.
Epiglottitis—A bacterial infection that affects the
epiglottis. The epiglottis is a flap of tissue that prevents
food and fluid from entering the trachea. The infection causes it to become swollen, potentially blocking
the airway. Other symptoms include a high fever,
nonbarking cough, muffled voice, and an inability
to swallow properly (possibly indicated by drooling).
Glucocorticoid—A hormone that helps in digestion of carbohydrates and reduces inflammation.
Larynx—Commonly called the voice box, it is the
area of the trachea that contains the vocal cords.
Stridor—The medical term used to describe the highpitched or rasping noise made when air is inhaled.
Trachea—Commonly called the windpipe, it is the
air pathway that connects the nose and mouth to
the lungs.

rotundifolia), thyme (Thymus vulgaris), and wild
cherry bark (Prunus serotina). Homeopathic medicine
can be very effective in treating cases of croup.
Choosing the correct remedy (a common choice is
aconite or monkshood, Aconitum napellus) is always
the key to the success of this type of treatment.

Definition
Cryoglobulin is an abnormal blood protein associated with several diseases. Testing for cryoglobulin
is done when a person has symptoms of this protein
or is being evaluated for one of the associated
diseases.

Purpose
Cryoglobulin clumps in cold temperatures. This
physical characteristic causes people with cryoglobulin to have symptoms during cold weather: blanching,
numbness, and pain in their fingers or toes (Raynaud’s
phenomenon); bleeding into the skin (purpura); and
pain in joints (arthralgia). People with these symptoms
or any other symptoms that appear in cold weather
should be tested for cryoglobulin.
Diseases that cause the body to make extra or
abnormal proteins are often associated with cryoglobulin. These diseases include cancers involving white
blood cells, infections, autoimmune disorders, and
rheumatoid diseases.
This test provides information about the cause of
symptoms in a person who already has a disease process. It does not diagnose a specific disease or monitor
the course of a disease.

Precautions
This test is not a screening test for disease in a
person without symptoms.

Prognosis
Croup is a temporary condition and children typically recover completely within three to six days.
Children can experience one or more episodes of
croup during early childhood; however, croup is rarely
a dangerous condition.

Prevention
Croup is caused by highly transmissible viruses
and is often difficult to impossible to prevent.
Resources
PERIODICALS

Kirn, Timothy F. ‘‘Cool Mist Therapy is Losing Credibility
for Croup: Steroids or Even Epinephrine May Be
Needed.’’ Pediatric News March 2004: 10–11.

Julia Barrett
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Description
Laboratory testing for cryoglobulin is based on
the fact that cryoglobulin clumps when cooled and
dissolves when warmed. The test is done on a person’s
serum (the yellow liquid part of blood that separates
from the cells after the blood clots). The serum is kept
warm from the time drawn until the cells and the
serum are separated in the laboratory. The serum is
placed at 33.8  F (1  C) for one to seven days. If there
is clumping, cryoglobulins are present. The amount
of cryoglobulins is determined by measuring the
amount of clumping. Negative tests are checked
through seven days.
Additional testing is done to find out what kind of
cryoglobulin protein is present. There are three kinds
of cryoglobulin, each associated with different
diseases.
1063

Cryoglobulin test

I Cryoglobulin test

KEY TERMS

Cryotherapy

Resources

KEY TERMS
Cryoglobulin—An abnormal blood protein associated with several diseases. It is characterized by
its tendency to clump in cold temperatures.

BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Nancy J. Nordenson

Cryosurgery see Cryotherapy
The test, also called the cold sensitivity antibodies
test, is covered by insurance when medically necessary.
Results are usually available the following day.

Preparation
This test requires 15–20 mL of blood. A healthcare worker ties a tourniquet on the person’s upper
arm, locates a vein in the inner elbow region, and
inserts a needle into that vein. Vacuum action draws
the blood through the needle into an attached tube.
Collection of the sample takes only a few minutes. The
blood must be kept warm, at body temperature, until
the laboratory can separate the cells from the serum.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve
discomfort.

Normal results
Negative or absent.

Abnormal results
If the person has cryoglobulin, the amount is
reported. Larger amounts of cryoglobulin are associated with cancers or abnormalities involving white
blood cells, moderate amounts are associated with
autoimmune disorders and rheumatoid diseases, and
smaller amounts are associated with infections.
The type of cryoglobulin is also reported. Type I
cryoglobulin, also called monoclonal cryoglobulinemia, is found in cancers or abnormalities of white
blood cells. Type II, also called mixed cryoglobulinemia, is associated with autoimmune disorders, rheumatoid diseases, and infections, particularly chronic
hepatitis B.
The physician must interpret the cryoglobulin
result along with other test results and the patient’s
clinical condition and medical history.
1064

I Cryotherapy
Definition
Cryotherapy is a technique that uses an extremely
cold liquid or instrument to freeze and destroy abnormal skin cells that require removal. The technique has
been in use since the turn of the century, but modern
techniques have made it widely available to dermatologists and primary care doctors. The technique is also
called cryosurgery.

Purpose
Cryotherapy can be employed to destroy a variety
of benign skin growths, such as warts, pre-cancerous
lesions (such as actinic keratoses), and malignant
lesions (such as basal cell and squamous cell cancers).
The goal of cryotherapy is to freeze and destroy targeted skin growths while preserving the surrounding
skin from injury.

Precautions
Cryotherapy is not recommended for certain
areas of the body because of the danger of destruction
of tissue or unacceptable scarring. These areas include:
skin that overlies nerves, the corners of the eyes, the
fold of skin between the nose and lip, the skin surrounding the nostrils, and the border between the lips
and the rest of the face. Lesions that are suspected or
known to be malignant melanoma should not be treated with cryotherapy, but should instead be removed
surgically. Similarly, basal cell or squamous cell carcinomas that have reappeared at the site of a previously
treated tumor should also be removed surgically. If it
remains unclear whether a growth is benign or malignant, a sample of tissue should be removed for analysis
(biopsy) by a pathologist before any attempts to
destroy the lesion with cryotherapy. Care should be
taken in people with diabetes or certain circulation
problems when cryotherapy is considered for growths
located on their lower legs, ankles, and feet. In these
GALE ENCYCLOPEDIA OF MEDICINE

Description
There are three main techniques to performing
cryotherapy. In the simplest technique, usually
reserved for warts and other benign skin growths, the
physician will dip a cotton swab or other applicator
into a cup containing a ‘‘cryogen,’’ such as liquid
nitrogen, and apply it directly to the skin growth to
freeze it. At a temperature of –320  F (–196  C), liquid
nitrogen is the coldest cryogen available. The goal is to
freeze the skin growth as quickly as possible, and then
let it thaw slowly to cause maximum destruction of the
skin cells. A second application may be necessary
depending on the size of the growth. In another
cryotherapy technique, a device is used to direct a
small spray of liquid nitrogen or other cryogen directly
onto the skin growth. Freezing may last from five to
20 seconds, depending on the size of the lesion. A
second freeze-thaw cycle may be required.
Sometimes, the physician will insert a small needle
connected to a thermometer into the lesion to make
certain the lesion is cooled to a low enough temperature to guarantee maximum destruction. In a third
option, liquid nitrogen or another cryogen is circulated through a probe to cool it to low temperatures.
The probe is then brought into direct contact with the
skin lesion to freeze it. The freeze time can take two to
three times longer than with the spray technique.

Preparation
Extensive preparation prior to cryotherapy is not
required. The area to be treated should be clean and
dry, but sterile preparation is not necessary. Patients
should know that they will experience some pain at the
time of the freezing, but local anesthesia is usually not
required. The physician may want to reduce the size of
certain growths, such as warts, prior to the cryotherapy procedure, and may have patients apply salicylic
acid preparations to the growth over several weeks.
Sometimes, the physician will pare away some of the
tissue using a device called a curette or a scalpel.

Aftercare
Redness, swelling, and the formation of a blister
at the site of cryotherapy are all expected results of the
treatment. A gauze dressing is applied and patients
should wash the site three or four times daily while
fluid continues to ooze from the wound, usually for
five to 14 days. A dry crust then forms that falls off by
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Actinic keratosis—A crusty, scaly pre-cancerous
skin lesion caused by damage from the sun.
Frequently treated with cryotherapy.
Basal cell cancer—The most common form of skin
cancer; it usually appears as one or several nodules
having a central depression. It rarely spreads
(metastisizes), but is locally invasive.
Cryogen—A substance with a very low boiling
point, such as liquid nitrogen, used in cryotherapy
treatment.
Melanoma—The most dangerous form of skin cancer. It should not be treated with cryotherapy, but
should be removed surgically instead.
Squamous cell cancer—A form of skin cancer that
usually originates in sun-damaged areas or preexisting lesions; at first local and superficial, it
may later spread to other areas of the body.

itself. Wounds on the head and neck may take four to
six weeks to heal, but those on the body, arms, and legs
can take longer. Some patients experience pain at the
site following the treatment. This can usually be eased
with acetaminophen (Tylenol), though in some cases a
stronger pain reliever may be required.

Risks
Cryotherapy poses little risk and can be welltolerated by elderly and other patients who are not
good candidates for other surgical procedures. As with
other surgical procedures, there is some risk of scarring, infection, and damage to underlying skin and
tissue. These risks are generally minimal in the hands
of experienced users of cryotherapy.

Normal results
Some redness, swelling, blistering and oozing of
fluid are all common results of cryotherapy. Healing
time can vary by the site treated and the cryotherapy
technique used. When cryogen is applied directly to
the growth, healing may occur in three weeks.
Growths treated on the head and neck with the spray
technique may take four to six weeks to heal; growths
treated on other areas of the body may take considerably longer. Cryotherapy boasts high success rates
in permanently removing skin growths; even for
malignant lesions such as squamous cell and basal
cell cancers, studies have shown a cure rate of up to
1065

Cryotherapy

patients, healing can be poor and the risk of infection
can be higher than for other patients.

Cryptococcosis

98%. For certain types of growths, such as some forms
of warts, repeat treatments over several weeks are
necessary to prevent the growth’s return.

Abnormal results
Although cryotherapy is a relatively low risk procedure, some side effects may occur as a result of the
treatment. They include:


Infection. Though uncommon, infection is more
likely on the lower legs where healing can take several
months.



Pigmentary changes. Both hypopigmentation
(lightening of the skin) and hyperpigmentation (darkening of the skin) are possible after cryotherapy.
Both generally last a few months, but can be longer
lasting.



Nerve damage. Though rare, damage to nerves is
possible, particularly in areas where they lie closer
to the surface of the skin, such as the fingers, the
wrist, and the area behind the ear. Reports suggest
this will disappear within several months.

Resources
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
American Society for Dermatologic Surgery. 930 N.
Meacham Road, PO Box 4014, Schaumburg, IL 601684014. (847) 330-9830. <http://www.asds-net.org>.

Richard H. Camer

I Cryptococcosis
Definition
Cryptococcosis is an infection caused by inhaling
the fungus Cryptococcus neoformans. It is one of the
diseases most often affecting AIDS patients.
Cryptococcosis may be limited to the lungs, but frequently spreads throughout the body. Although
almost any organ can be infected, the fungus is often
fatal if it infects the nervous system where it causes an
inflammation of the membranes covering the brain
and spinal cord (meningitis).
1066

Description
The fungus causing cryptococcis, C. neoformans,
is found worldwide in soil contaminated with pigeon
or other bird droppings. It has also been found on
unwashed raw fruit. Cryptococcosis is a rare disease
in healthy individuals, but is the most common fungal
infection affecting people with AIDS.
People with Hodgkin’s disease or who are taking
large doses of drugs that suppress the functioning of
the immune system (corticosteroids, chemotherapy
drugs) are also more susceptible to cryptococcal infection. Cryptococcosis is also called cryptococcal
meningitis (when the brain is infected), BusseBuschke disease, European blastomycosis, torular
meningitis, or torulosis.

Causes and symptoms
Once the cryptococcal fungus reaches the lungs,
three things can happen. The immune system can heal
the body without medical intervention, the disease can
stay localized in the lungs, or it can spread throughout
the body. In healthy people with normally functioning
immune systems, the body usually heals itself, and the
infected person notices no symptoms and has no complications (asymptomatic). The disease does not
spread from one person to another.
Cryptococcosis is an opportunistic infection that
puts people with immune system diseases at higher risk
of developing more serious forms of the disease. In the
United States, 6–10% of all patients with AIDS get
cryptococcosis.
If the body does not heal itself, the fungus begins
to grow in the lungs and form nodules that can be seen
on chest x rays. In the early stages of infection, an
individual usually only exhibits symptoms of a respiratory infection, such as a dry cough, so the disease is
rarely diagnosed.
The fungus can remain dormant in the lungs and
produce an active infection later if the immune system
is weakened. If the disease becomes active, it can cause
cryptococcal pneumonia in the lungs. Unfortunately,
however, cryptococcal pneumonia has symptoms
similar to other pneumonias (cough, chest pain, difficulty breathing), making it difficult to accurately diagnose. The infection can spread to other parts of the
body, particularly the brain and central nervous
system.
Most patients are not diagnosed as having cryptococcosis until they show signs of cryptococcal
meningitis, or infection of the membranes surrounding the brain and spinal cord. Symptoms appear
GALE ENCYCLOPEDIA OF MEDICINE

This lesion appearing on this person’s body is due to
exposure of the C. neoformans fungus. (Photo Researchers,
Inc. Reproduced by permission.)

gradually over a period of two to four weeks. Fever
and headache are the most common symptoms, occurring in about 85% of patients. Nausea, vomiting,
unwanted weight loss, and fatigue are also common.
Other symptoms seen in 25–30% of patients are
blurred vision, stiff neck, aversion to light, and seizures. Since the symptoms of classic meningitis, such
as stiff neck and aversion to light, do not occur in
many patients, diagnosis is often delayed. In addition
to meningitis, inflammation of the brain (encephalitis)
and brain lesions called cryptococcomas or tortulomas can also develop.
In addition to the brain, the cryptococcal infection can spread to the kidneys, bone marrow, heart,
adrenal glands, lymph nodes, urinary tract, blood,
and skin. Often times preceding the development of
cryptococcal meningitis, painless rashes and lesions
that mimic other skin diseases, such as molluscum
contagiosum, may develop. A small percentage of
patients with brain infections show infections in
other organs as well.

Diagnosis
Physicians who regularly work with AIDS
patients have the most experience in diagnosing
cryptococcosis. The preferred methods of diagnosis
use simple and very accurate blood and cerebrospinal
fluid (CSF) tests that detect the presence of an antigen produced by the fungus. The cerebrospinal fluid
test is generally more sensitive to detecting the meningitis form of the infection. CSF is collected during a
procedure called a lumbar puncture, during which an
anesthetic is applied to a small area of the back near
the spine and a needle is used to withdraw a sample of
GALE ENCYCLOPEDIA OF MEDICINE

Another way to diagnose cryptococcosis is to culture a sample of sputum, tissue from a lung biopsy, or
CSF in the laboratory to isolate the fungus. Cultures
are also done to assess the effectiveness of treatment.
Chest x rays are useful in assessing lung damage
and may reveal a single mass or multiple distinct
nodules, but the x ray alone does not lead to a definitive diagnosis of cryptococcosis.

Treatment
Once cryptococcosis is diagnosed, treatment
begins with amphotericin B (Fungizone), sometimes
in combination with 5-flucytosine (Ancobon).
Amphotericin B is a powerful fungistatic drug with
potentially toxic side effects, such as kidney toxicity
and lower concentrations of an important blood component called hemoglobin. This medication can also
cause fever, chills, nausea and vomiting, diarrhea,
headache, and muscle aches. Treatment is generally
given intravenously during a hospital stay and continues until the patient is stable or improving (no more
than two to three weeks). 5-flucytosine is given orally.
Patients may also receive other medication to minimize the side effects from these drugs.
Amphotericin B, with or without 5-flucytosine, is
given for several weeks until the patient is stable, after
which the patient receives oral fluconazole (Diflucan).
Fluconazole is a broad-spectrum antifungal drug
with few serious side effects. Patients with AIDS
must continue taking fluconazole for the rest of their
lives to prevent a relapse of cryptococcosis. Sometimes
fluconazole is given to patients with advanced AIDS
as a preventative (prophylactic) measure.
Because of the high cost of fluconazole, the manufacturer of the drug, Pfizer, has established a financial
assistance plan to make the drug available at lower cost
to those who meet certain criteria. Patients needing this
drug should ask their doctors about this program.
1067

Cryptococcosis

cerebrospinal fluid from the space between the vertebrae and the spinal cord. Once obtained, a small
amount of ink (called India ink) is added to a sample
of CSF or a sample prepared from skin lesions. If the
fungus is present, it will become visible when the ink
binds to the capsule or covering that surrounds the
fungus. Faster results are obtained with the India ink
test, but it is less accurate than the blood test (75–
85% accuracy compared to 99% accuracy with the
blood test) because some strains are not visible using
this method. Antigen tests are routinely recommended for non-symptomatic patients with advanced
AIDS.

Cryptococcosis

KEY TERMS
Adrenal gland—A pair of organs located above the
kidneys. The outer tissue of the gland produces the
hormones epinephrine (adrenaline) and norepinephrine, while the inner tissue produces several
steroid hormones.
Amphotericin B (Fengizone)—An antifungal medication, prescribed for topical or systemic use in treating fungal infections.
Antibody—A specific protein produced by the
immune system in response to a specific foreign protein or particle called an antigen.
Antigen—A foreign protein or particle capable of
eliciting an immune response.
Asymptomatic—Persons who carry a disease but
who do not exhibit symptoms of the disease are said
to be asymptomatic.
Biopsy—The removal of a tissue sample for diagnostic purposes.
Cerebrospinal fluid (CSF)—The clear fluid that surrounds the spinal cord and brain and acts as a shock
absorber.
Corticosteroids—A group of hormones produced
naturally by the adrenal gland or manufactured
synthetically. They are often used to treat inflammation. Examples include cortisone and prednisone.
Encephalitis—Inflammation of the brain.

Prognosis
Untreated cryptococcosis is always fatal. The
acute mortality rate for patients with AIDS is 10–
25%. Most deaths are attributable to cryptococcal
meningitis and occur within two weeks after diagnosis. For AIDS patients who do not receive continued
suppressive therapy (fluconazole), the relapse rate
is 50–60% within six months and a shortened life
expectancy. Once the cryptococcosis infection has
been successfully treated, individuals may be left
with a variety of neurologic symptoms, such as
weakness, headache, and hearing or visual loss. In
addition, fluid may accumulate around the brain
(hydrocephalus).

Prevention
The best way to prevent cryptococcosis is to stay
free of HIV infection. People with suppressed immune
systems should try to stay away from areas
1068

Hodgkin’s disease—A disease that causes chronic
inflammation of the lymph nodes, spleen, liver and
kidneys. It is also called malignant lymphoma.
Hydrocephalus—Build-up of fluid around the brain.
Immunocompromised—A state in which the immune
system is suppressed or not functioning properly.
India ink test—A diagnostic test used to detect the
cryptococcal organism C. neoformans. A dye, called
India ink, is added to a sample of CSF fluid, and if the
fungi is present, they will become visible as the dye
binds to the capsule surrounding the fungus.
Lumbar puncture—Also called a spinal tap, a procedure in which a thin needle is used to withdraw a
sample of cerebrospinal fluid for diagnostic purposes
from the area surrounding the spine.
Meningitis—Inflammation of the membranes covering the brain and spinal cord called the meninges.
Molluscum contagiosum—A disease of the skin and
mucuous membranes, caused by a poxvirus and
found all over the world.
Opportunistic infection—An infection that is normally
mild in a healthy individual, but which takes advantage
of an ill person’s weakened immune system to move
into the body, grow, spread, and cause serious illness.
Pneumonia—Inflammation of the lungs, typically
caused by a virus, bacteria, or other organism.

contaminated with pigeon or other bird droppings,
such as the attics of old buildings, barns, and areas
under bridges where pigeons roost.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
National AIDS Clearinghouse. (800) 458-5231.
National AIDS Hotline. (800) 342-AIDS.
Project Inform. 205 13th Street, #2001, San Francisco, CA
94103. (800) 822-7422. <http://www.projinf.org>.

Tish Davidson, A.M.

Cryptococcus neoformans infection see
Cryptococcosis
Cryptorchidism see Undescended testes
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Cryptosporidiosis refers to infection by the sporeforming protozoan known as Cryptosporidia.
Protozoa are a group of parasites that infect the
human intestine, and include the better known
Giardia. Cryptosporidia was first identified in 1976 as
a cause of disease in humans.

Description
Cryptosporidia are normally passed in the feces of
infected persons and animals in the form of cysts. The
cysts can remain in the ground and water for months,
and when ingested produce symptoms after maturing
in the intestine and the bile ducts. When viewed under
the microscope, they appear as small bluish-staining
round bodies. Most common sources of infection are
other humans, water supplies, or reservoirs. These are
contaminated by animals that defecate in these areas.
An outbreak in Milwaukee in 1993 in which over
400,000 persons were affected was traced to the city’s
water supply. Cysts of Cryptosporidia are extremely
resistant to the disinfectants that are commonly used
in most water treatment plants and are incompletely
removed by filtration.
Most persons who experience significant symptoms have an altered immune system, and suffer
from diseases such as AIDS and cancer. However, as
shown in the Milwaukee outbreak, even those with
normal immunity can experience symptoms.

Causes and symptoms
Cysts of Cryptosporidia mature in the intestine
and bile ducts within three to five days of ingestion.
As noted, large-scale infections from contaminated
water supplies has been documented. However,
human to human transmission (such as occurs in day
care centers or through sexual behavior) is also an
important cause.
Many individuals can be infected without any illness, but the major symptom is diarrhea, which is often
watery and incapacitating. Dehydration, low-grade
fever, nausea, and abdominal cramps are frequent.
In those with a normal immune system, the disease usually lasts about 10 days. For patients with
altered immunity (immunocompromised), the story
is quite different, with diarrhea becoming chronic,
debilitating, and even fatal.

GALE ENCYCLOPEDIA OF MEDICINE

Dehydration and malnutrition are the most common effects of infection. In about 20% of AIDS
patients, bile duct infection also occurs and causes
symptoms similar to gallbladder attacks. Eighty percent or more of those with infection of the bile ducts
die from the disease. The lungs and pancreas are also
sometimes involved. Cryptosporidia are just one cause
of the diarrhea wasting syndrome in AIDS, which
results in severe weight loss and malnutrition.

Diagnosis
This is based on either finding the characteristic
cysts in stool specimens, or on biopsy of an infected
organ, such as the intestine.

Treatment
The first aim of treatment is to avoid dehydration.
Oral Rehydration Solution (ORS) or intravenous fluids
may be needed. Medications used to treat diarrhea by
decreasing intestinal motility (Anti-Motility Agents),
such as loperamide or diphenoxylate, are also useful,
but should only be used with the advice of a physician.
Treatment aimed directly at Cryptosporidia is only
partially effective, and rarely eliminates the organism.
The medication most commonly used is paromomycin
(Humatin), but others are presently under evaluation.

Prognosis
Cryptosporidia rarely cause a serious disease in
persons with normal immune systems. Replacement
of fluids is all that is usually needed. On the other
hand, those with altered immune systems often suffer
for months to years. Paramomycin and other drugs
have been able to improve symptoms in over half of
those treated. Unfortunately, many organisms are
resistant, and recurrence is frequent.

Prevention
The best way to prevent cryptosporidiosis is to
minimize exposure to cysts from infected humans
and animals. Proper hand washing technique, especially in day care centers, is recommended.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
1069

Cryptosporidiosis

I Cryptosporidiosis

Complications

CT-guided biopsy

KEY TERMS
Anti-motility medications—Medications such as
loperamide (sold as Imodium), dephenoxylate
(sold as Lomotil), or medications containing
codeine or narcotics that decrease the ability of
the intestine to contract. This can worsen the
condition of a patient with dysentery or colitis.
Cyst—A protective sac that includes either fluid or
the cell of an organism. The cyst enables many
organisms to survive in the environment for long
periods of time without need for food or water.
Immunocompromised—A change or alteration of
the immune system that normally serves to fight off
infections and other illnesses. This can involve
changes in antibodies that the body produces
(hygogammaglobulinemia), or defect in the cells
that partake in the immune response. Diseases
such as AIDS and cancer exhibit changes in the
body’s natural immunity.
Oral Rehydration Solution (ORS)—A liquid
preparation developed by the World Health
Organization that can decrease fluid loss in persons
with diarrhea. Originally developed to be prepared
with materials available in the home, commercial
preparations have recently come into use.
Parasite—An organism that lives on or in another
and takes nourishment (food and fluids) from that
organism.
Protozoa—Group of extremely small single cell
(unicellular) or acellular organisms that are found
in moist soil or water. They tend to exist as
parasites, living off other life forms.
Spore—A resistant form of certain species of
bacteria, protozoa, and other organisms.

Definition
Computed tomography (CT) is a process that
images anatomic information from a cross-sectional
plane of the body. Biopsy is the process of taking a
sample of tissue from the body for analysis. CT is
commonly used in biopsies to provide images that
help guide the tools or equipment necessary to perform the biopsy to the appropriate area of the body.

Purpose
CT is used in the process of performing a biopsy,
such as a needle biopsy, in order to guide the needle to
the site of the biopsy and to provide rapid and precise
localization of the needle. CT enables imaging of areas
that are normally beyond visible boundaries. This
enables the physician to see the target area clearly
and help to ensure that the tissue being removed is
from the target lesion.

Precautions
The patient that suffers from claustrophobia will
want to discuss this with their physician. This procedure involves the patient being placed into the CT
scanner, typically a small, enclosed area. Depending
on the specific type of biopsies being performed, certain anesthetics will be used, so discuss drug allergies
with your physician.

Description
CT can assist in providing more enhanced images
of a suspicious lesion. It helps to determine whether a
tumor is truly solitary or not. CT can characterize the
tumor and aid in the estimation of malignancy.

Preparation

OTHER

‘‘Cryptosporidiosis.’’ Centers for Disease Control. <http://
www.cdc.gov/ncidod/diseases/crypto/crypto.htm>.
Vakil, Nimish B., et al. ‘‘Biliary Cryptosporidiosis in HIVInfected People after the Waterborne Outbreak of
Cryptosporidiosis in Milwaukee.’’New England Journal
of Medicine Online. <http://content.nejm.org>.

David Kaminstein, MD

CSF analysis see Cerebrospinal fluid (CSF)
analysis
1070

I CT-guided biopsy

Since there are many different types of biopsies,
you should follow the instructions from your physician
to prepare for your CT-guided biopsy. Patients who
suffer from claustrophobia should discuss their concerns with the physician. In some cases, medicine can
be given that will relax the patient during the procedure.

Risks
CT-guided biopsy does not increase the risk of the
biopsy any more than any other radiologic imaging
such as x ray.
GALE ENCYCLOPEDIA OF MEDICINE

not be influenced by verbal ability, cultural climate, or
educational level.

Lesion—A pathologic change in tissues.
Malignancy—A locally invasive and destructive
growth.

Normal results
Because the area being biopsied, as well as the
specific type of biopsy procedure can vary, results
will vary. Before undergoing the procedure, notification procedure should be clearly defined.
Resources
BOOKS

Stedman’s Medical Dictionary. 27th ed. Philadelphia:
Lippincot Williams & Wilkins, 2000.
Tierney, Lawrence, et. al. Current Medical Diagnosis and
Treatment. Los Altos: Lange Medical Publications,
2001.
PERIODICALS

Garpestad, E., et. al. ‘‘CT Fluoroscopy Guidance for
Transbronchial Needle Aspiration.’’ Chest 119
(February 2001).
Shaffer, K. ‘‘Role of Radiology for Imaging and Biopsy of
Solitary Pulmonary Nodules.’’ Chest 116 (December
1999).
White, C.S., C.A. Meyer, and P. A. Templeton.
‘‘CT Fluoroscopy for Throacic Interventional
Procedures.’’ Radiologic Clinics of North America
38 (March 2000).
White, C.S., et. al. ‘‘Transbronchial Needle Aspiration:
Guidance with CT Fluoroscopy.’’ Chest 118
(December 2000).

Kim A. Sharp, M.Ln.

CT-myelogram see Myelography
CT scan see Computed tomography scans

I Culture-fair test
Definition
A culture-fair test is test designed to be free of
cultural bias, as far as possible, so that no one culture
has an advantage over another. The test is designed to
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
The purpose of a culture-fair test is to eliminate any
social or cultural advantages, or disadvantages, that a
person may have due to their upbringing. The test can
be administered to anyone, from any nation, speaking
any language. A culture-fair test may help identify
learning or emotional problems. The duration of the
test varies for the individual types of tests available, but
the time is approximately between 12–18 minutes per
section (a test usually has two to four sections).
A culture-fair test is often administered by
employers in order to determine the best location for
new employees in a large company. The wide variety
of culture-fair tests available allows the administrator
to select which area is most vital, whether it be general
intelligence, knowledge of a specific area, or emotional
stability.

Precautions
There is doubt as to whether any test can truly be
culturally unbiased or can ever be made completely
fair to all persons independent of culture. There are no
other precautions.

Description
A culture-fair test is a non-verbal paper-pencil test
that can be administered to patients as young as four
years old. The patient only needs the ability to recognize shapes and figures and perceive their respective
relationships. Some examples of tasks in the test may
include:


completing series



classifying



solving matrices



evaluating conditions

The culture-fair test is also often referred to as a
culture-free test or unbiased test. There are many variations of the test including class, economic, and intelligence tests. The threading theme among the various
tests is their design to be culturally unbiased.

Preparation
The only preparation necessary to administer the
test is pre-ordered materials and a quiet and secluded
location for the duration of the test.
1071

Culture-fair test

KEY TERMS

Cushing’s syndrome

Aftercare
Post-test treatment depends on the results of the
test and the specifics of the individual patient. Any
further treatment is best prescribed by the doctor.

Risks
There are no risks associated with the culture-fair
test.

Normal results
The results can be compared to the key that comes
with the purchase of a culture-fair test. All results
should be compared to the included key.
Resources

the base of the brain. After the hypothalamus (the
part of the brain containing secretions important
to metabolic activities) sends ‘‘releasing hormones’’
to the pituitary gland, the pituitary secretes a hormone called adrenocorticotropic hormone (ACTH).
The ACTH then travels through the bloodstream
to the adrenal cortex, where it encourages the production and release of cortisol (sometimes called
the ‘‘stress’’ hormone) and other adrenocortical
hormones.
Cortisol, a very potent glucocorticoid—a group
of adrenocortical hormones that protects the body
from stress and affect protein and carbohydrate metabolism—is involved in regulating the functioning of
nearly every type of organ and tissue in the body, and
is considered to be one of the few hormones absolutely
necessary for life. Cortisol is involved in:

BOOKS


complex processing and utilization of many nutrients, including sugars (carbohydrates), fats, and
proteins



normal functioning of the circulatory system and the
heart



functioning of muscles



normal kidney function



production of blood cells



I Cushing’s syndrome

normal processes involved in maintaining the
skeletal system



proper functioning of the brain and nerves

Definition



normal responses of the immune system

Maddox, Taddy. Test. 4th ed. Austin, Texas: Pro-Ed
Inc., 1997.

Michael Sherwin Walston
Ronald Watson, PhD

Cultures for sexually transmitted diseases see
Sexually transmitted diseases cultures

Cushing’s syndrome is a relatively rare endocrine (hormonal) disorder resulting from excessive
exposure to the hormone cortisol. The disorder,
which leads to a variety of symptoms and physical
abnormalities, is most commonly caused by taking
medications containing the hormone over a long
period of time. A more rare form of the disorder
occurs when the body itself produces an excessive
amount of cortisol.

Description
The adrenals are two glands, each of which is
perched on the upper part of the two kidneys. The
outer part of the gland is known as the cortex; the
inner part is known as the medulla. Each of these
parts of the adrenal gland is responsible for producing
different types of hormones. Regulation of hormone
production and release from the adrenal cortex
involves the pituitary gland, a small gland located at
1072

Cushing’s syndrome, also called hypercortisolism, has an adverse effect on all of the processes
described above. The syndrome occurs in approximately 10 to 15 out of every one million people per
year, usually striking adults between the ages of 20
and 50.

Causes and symptoms
The most common cause of Cushing’s syndrome
is the long-term use of glucocorticoid hormones in
medications. Medications such as prednisone are
used in a number of inflammatory conditions. Such
conditions include rheumatoid arthritis, asthma,
vasculitis, lupus, and a variety of other autoimmune
disorders in which the body’s immune cells accidentally attack some part of the body itself. In these
disorders, the glucocorticoids are used to dampen the
immune response, thereby decreasing damage to the
body.
GALE ENCYCLOPEDIA OF MEDICINE



a pituitary tumor producing abnormally large quantities of ACTH



the abnormal production of ACTH by some source
other than the pituitary



a tumor within the adrenal gland overproducing
cortisol

Although it is rare, about two-thirds of endogenous (occurring within the body rather than from a
source outside the body, like a medication) Cushing’s
syndrome which is caused by excessive secretion of
ACTH by a pituitary tumor, usually an adenoma
(noncancerous tumor). The pituitary tumor causes
increased growth of the adrenal cortex (hyperplasia)
and increased cortisol production. Cushing’s disease
affects women more often than men.
Tumors in locations other than the pituitary
can also produce ACTH. This is called ectopic
ACTH syndrome (‘‘ectopic’’ refers to something
existing out of its normal place). Tumors in the lung
account for more than half of all cases of ectopic
ACTH syndrome. Other types of tumors that may
produce ACTH include tumors of the thymus, the
pancreas, the thyroid, and the adrenal gland. Nearly
all adrenal gland tumors are benign (noncancerous),
although in rare instances a tumor may actually be
cancerous.
Symptoms of cortisol excess (resulting from medication or from the body’s excess production of the
hormone) include:


weight gain



an abnormal accumulation of fatty pads in the face
(creating the distinctive ‘‘moon face’’ of Cushing’s
syndrome); in the trunk (termed ‘‘truncal obesity’’);
and over the upper back and the back of the neck
(giving the individual what has been called a ‘‘buffalo
hump’’)



purple and pink stretch marks across the abdomen
and flanks



high blood pressure



weak, thinning bones (osteoporosis)



weak muscles



low energy



thin, fragile skin, with a tendency toward both bruising and slow healing



abnormalities in the processing of sugars (glucose),
with occasional development of actual diabetes

GALE ENCYCLOPEDIA OF MEDICINE



kidney stones



increased risk of infections



emotional disturbances, including mood swings,
depression, irritability, confusion, or even a complete
break with reality (psychosis)



irregular menstrual periods in women



decreased sex drive in men and difficulty maintaining
an erection



abormal hair growth in women (in a male pattern, such as in the beard and mustache area), as
well as loss of hair from the head (receding hair
line).

Diagnosis
Diagnosing Cushing’s syndrome can be complex.
Diagnosis must not only identify the cortisol excess,
but also locate its source. Many of the symptoms listed
above can be attributed to numerous other diseases.
Although a number of these symptoms seen together
would certainly suggest Cushing’s syndrome, the
symptoms are still not specific to Cushing’s syndrome.
Following a review of the patient’s medical history,
physical examination, and routine blood tests, a series
of more sophisticated tests is available to achieve a
diagnosis.
24-hour free cortisol test
This is the most specific diagnostic test for identifying Cushing’s syndrome. It involves measuring the
amount of cortisol present in the urine over a 24-hour
period. When excess cortisol is present in the bloodstream, it is processed by the kidneys and removed as
waste in the urine. This 24-hour free cortisol test
requires that an individual collect exactly 24-hours’
worth of urine in a single container. The urine is then
analyzed in a laboratory to determine the quantity of
cortisol present. This technique can also be paired with
the administration of dexamethasone, which in a normal individual would cause urine cortisol to be very
low. Once a diagnosis has been made using the
24-hour free cortisol test, other tests are used to find
the exact location of the abnormality causing excess
cortisol production.
Dexamethasone suppression test
This test is useful in distinguishing individuals
with excess ACTH production due to a pituitary adenoma from those with ectopic ACTH-producing
tumors. Patients are given dexamethasone (a synthetic
glucocorticoid) orally every six hours for four days.
1073

Cushing’s syndrome

Cushing’s syndrome can also be caused by three
different categories of disease:

Cushing’s syndrome

produce false-negative results. Thus, patients are
usually advised to stop taking these drugs at least
one week prior to the test.
Corticotropin-releasing hormone (CRH)
stimulation test
The CRH stimulation test is given to help distinguish between patients with pituitary adenomas and
those with either ectopic ACTH syndrome or cortisolsecreting adrenal tumors. In this test, patients are
given an injection of CRH, the corticotropin-releasing
hormone that causes the pituitary to secrete ACTH. In
patients with pituitary adenomas, blood levels of
ACTH and cortisol usually rise. However, in patients
with ectopic ACTH syndrome, this rise is rarely seen.
In patients with cortisol-secreting adrenal tumors, this
rise almost never occurs.
Petrosal sinus sampling

Woman with Cushing’s syndrome. (Photo Researchers, Inc.
Reproduced by permission.)

Low doses of dexamethasone are given during the
first two days; for the last two days, higher doses are
administered. Before dexamethasone is administered,
as well as on each day of the test, 24-hour urine collections are obtained.
Because cortisol and other glucocorticoids signal
the pituitary to decrease ACTH, the normal response
after taking dexamethasone is a drop in blood and
urine cortisol levels. Thus, the cortisol response to
dexamethasone differs depending on whether the
cause of Cushing’s syndrome is a pituitary adenoma
or an ectopic ACTH-producing tumor.
However, the dexamethasone suppression test
may produce false-positive results in patients with
conditions such as depression, alcohol abuse, high
estrogen levels, acute illness, and stress. On the other
hand, drugs such as phenytoin and phenobarbital may
1074

Although this test is not always necessary, it may
be used to distinguish between a pituitary adenoma
and an ectopic source of ACTH. Petrosal sinus
sampling involves drawing blood directly from veins
that drain the pituitary. This test, which is usually
performed with local anesthesia and mild sedation,
requires inserting tiny, flexible tubes (catheters)
through a vein in the upper thigh or groin area. The
catheters are then threaded up slowly until they reach
veins in an area of the skull known as the petrosal
sinuses. X rays are typically used to confirm the
correct position of the catheters. Often CRH is also
given during the test to increase the accuracy of
results.
When blood tested from the petrosal sinuses
reveals a higher ACTH level than blood drawn from
a vein in the forearm, the likely diagnosis is a pituitary
adenoma. When the two samples show similar levels
of ACTH, the diagnosis indicates ectopic ACTH
syndrome.
Radiologic imaging tests
Imaging tests such as computed tomography scans
(CT) and magnetic resonance imaging (MRI) are only
used to look at the pituitary and adrenal glands after
a firm diagnosis has already been made. The presence
of a pituitary or adrenal tumor does not necessarily
guarantee that it is the source of increased ACTH
production. Many healthy people with no symptoms
or disease whatsoever have noncancerous tumors in
the pituitary and adrenal glands. Thus, CT and MRI
is often used to image the pituitary and adrenal
glands in preparation for surgery.
GALE ENCYCLOPEDIA OF MEDICINE

The choice of a specific treatment depends on the
type of problem causing the cortisol excess. Pituitary
and adrenal adenomas are usually removed surgically.
Malignant adrenal tumors always require surgical
removal.
Treatment of ectopic ACTH syndrome also
involves removing all of the cancerous cells that are
producing ACTH. This may be done through surgery,
chemotherapy (using combinations of cancer-killing
drugs), or radiation therapy (using x rays to kill cancer
cells), depending on the type of cancer and how far it
has spread. Radiation therapy may also be used on the
pituitary (with or without surgery) for patients who
cannot undergo surgery, or for patients whose surgery
did not successfully decrease pituitary release of
ACTH.
There are a number of drugs that are effective in
decreasing adrenal production of cortisol. These medications include mitotane, ketoconazole, metyrapone,
trilostane, aminoglutethimide, and mifepristone.
These drugs are sometimes given prior to surgery in
an effort to reverse the problems brought on by cortisol excess. However, the drugs may also need to be
administered after surgery (sometimes along with
radiation treatments) in patients who continue to
have excess pituitary production of ACTH.
Because pituitary surgery can cause ACTH levels
to drop too low, some patients require short-term
treatment with a cortisol-like medication after surgery. Patients who need adrenal surgery may also
require glucocorticoid replacement. If the entire adrenal gland has been removed, the patient must take oral
glucocorticoids for the rest of his or her life.

Prognosis
Prognosis depends on the source of the problem.
When pituitary adenomas are identified as the source
of increased ACTH leading to cortisol excess, about
80% of patients are cured by surgery. When cortisol
excess is due to some other form of cancer, the prognosis depends on the type of cancer and the extent of
its spread.
Resources
BOOKS

Williams, Gordon H., and Robert G. Dluhy.
‘‘Hyperfunction of the Adrenal Cortex.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony S.
Fauci, et al. New York: McGraw-Hill, 1998.

KEY TERMS
Adenoma—A type of noncancerous (benign) tumor
that often involves the overgrowth of certain cells of
the type normally found within glands.
Adrenocorticotropic hormone (ACTH)—A pituitary hormone that stimulates the cortex of the adrenal glands to produce adrenal cortical hormones.
Cortisol—A hormone secreted by the cortex of the
adrenal gland. Cortisol regulates the function of
nearly every organ and tissue in the body.
Ectopic—In an abnormal position.
Endocrine—Pertaining to a gland that secretes
directly into the bloodstream.
Gland—A collection of cells whose function is to
release certain chemicals (hormones) that are
important to the functioning of other, sometimes
distantly located, organs or body systems.
Glucocorticoids—General class of adrenal cortical
hormones that are mainly active in protecting
against stress and in protein and carbohydrate
metabolism.
Hormone—A chemical produced in one part of the
body that travels to another part of the body in order
to exert its effect.
Hypothalamus—the part of the brain containing
secretions important to metabolic activities.
Pituitary—A gland located at the base of the brain,
the pituitary produces a number of hormones,
including hormones that regulate growth and
reproductive function.

PERIODICALS

Boscaro, Marco, Luisa Barzon, and Nicoletta Sonino. ‘‘The
Diagnosis of Cushing’s Syndrome: Atypical
Presentations and Laboratory Shortcomings.’’ Archives
of Internal Medicine 160 (2000): 3045-53.
Boscaro, Marco, Luisa Barzon, Francesco Fallo, and
Nicoletta Sonino. ‘‘Cushing’s Syndrome.’’ Lancet 357
(2001): 783-91.
Kirk, Lawrence F., Robert B. Hash, Harold P. Katner, and
Tom Jones. ‘‘Cushing’s Disease: Clinical Manifestations
and Diagnostic Evaluation.’’American Family Physician
62, no. 5 (September 1, 2001): 1119-27.
Newell-Price J., and A. Grossman. ‘‘Diagnosis and
Management of Cushing’s Syndrome.’’ Lancet 353
(1999): 2087-88.

Rosalyn Carson-DeWitt, MD
GALE ENCYCLOPEDIA OF MEDICINE

1075

Cushing’s syndrome

Treatment

Cutaneous larva migrans

I Cutaneous larva migrans
Definition
Cutaneous larvae migrans is a parasitic skin disease caused by a hookworm larvae that usually infests
dogs, cats, and other animals. Humans can pick up
the infection by walking barefoot on soil or beaches
contaminated with animal feces.

Description
Cutaneous larvae migrans (also called ‘‘creeping eruption’’ or ‘‘ground itch’’) is found in southeastern and Gulf states, and in tropical developing
countries.
The hookworms that cause the condition are
small, round blood-sucking worms that infest about
700 million people around the world. Cutaneous larvae migrans occurs most often among children, those
who crawl beneath raised buildings, and sunbathers
who lie down on wet sand contaminated with hookworm larvae.

Causes and symptoms
After an animal passes feces that are infested with
hookworm eggs, the eggs hatch into infective larvae
that are able to penetrate human skin (even through
solid material, such as a beach towel). The larvae are
commonly found in shaded, moist, or sandy areas
(such as beaches, a child’s sandbox, or areas underneath a house), where they are easily picked up by bare
feet or buttocks.
In minor infestations, there may be no symptoms
at all. In more severe cases, a red elevation of the skin
(papule) appears within a few hours after the larvae
have penetrated the skin. This usually arises first in
areas that are in contact with the soil, such as the feet,
hands, and buttocks.
Between a few days and a few months after infection, the larvae begin to migrate beneath the skin,
leaving extremely itchy red lines that may be accompanied by blisters. These red lines usually appear at the
top of the sole of the foot or on the buttocks.
Tyically, the larvae travel through the bloodstream, to the lungs, and then migrate into the
mouth where they are swallowed and attach to the
small intestine lining. There they mature into adult
worms. In cases where the larvae migrate through the
lungs, they can produce anemia, cough, and pneumonia, in addition to the itchy rash.
1076

Linear red rashes around a patient’s knee caused by burrowing larvae of the dog hookworm Ancylostoma braziliensis.
(Photograph by Dr. P. Marazzi, Custom Medical Stock Photo.
Reproduced by permission.)

KEY TERMS
Larvae—Immature forms of certain worms.

Diagnosis
The condition can be diagnosed by microscopic
inspection of feces which can reveal hookworm eggs.
In addition visual inspection of the skin would reveal
telltale itchy red lines and blisters.

Treatment
People without intestinal symptoms do not need
treatment, since the worms will eventually die or be
excreted. Thiabendazole or albendazole are used to
treat the infestation. Mild infections can be treated
by applying one of the drugs to the skin along the
tracks and the normal skin surrounding the area.
Thiabendazole also can be given internally, but taken
this way it can cause side effects including dizziness,
nausea, and vomiting

Prognosis
No matter how severe an infestation, with adequate treatment patients recover completely.
However, if the patient scratches the lesions open,
the areas can become vulnerable to bacterial infection.

Prevention
In the United States, the prevalence of dogs and
cats with hookworms is the reason why the infective
GALE ENCYCLOPEDIA OF MEDICINE

Human hookworm infestation can be prevented
by practicing good personal hygiene, deworming pets,
and not allowing children to play in potentially contaminated environments.
Resources
BOOKS

Turkington, Carol A., and Jeffrey S. Dover. Skin Deep: An
A-Z of Skin Disorders, Treatments and Health. 2nd ed.
New York: Facts on File, 1998.

Carol A. Turkington

I Cutaneous T-cell lymphoma
Definition
Cutaneous T-cell lymphoma (CTCL) is a malignancy of the T-helper (CD4+) cells of the immune
system.

Description
CTCL, also known as mycosis fungoides, is a
cancer of the white blood cells that primarily affects
the skin and only secondarily affects other sites. This
disease involves the uncontrollable proliferation of
T-lymphocytes known as T-helper cells, so named
because of their role in the immune response. T-helper
cells are characterized by the presence of a protein
receptor on their surface called CD4. Accordingly,
T-helper cells are said to be CD4+.
The proliferation of T-helper cells results in the
penetration, or infiltration, of these abnormal cells
into the epidermal layer of the skin. The skin reacts
with slightly scaling lesions that itch, although the sites
of greatest infiltration do not necessarily correspond
to the sites of the lesions. The lesions are most often
located on the trunk, but can be present on any part of
the body. In the most common course of the disease,
the patchy lesions progress to palpable plaques that
are deeper red and have more defined edges. As the
disease worsens, skin tumors develop that are often
mushroom-shaped, hence the name mycosis fungoides. Finally, the cancer progresses to extracutanous
involvement, often in the lymph nodes or the viscera.
GALE ENCYCLOPEDIA OF MEDICINE

CTCL is a rare disease, with an annual incidence
of about 0.29 cases per 100,000 persons in the United
States. It is about half as common in Eastern Europe.
However, this discrepancy may be attributed to a
differing physician awareness of the disease rather
than a true difference in occurrence. In the United
States, there are about 500–600 new cases a year and
about 100–200 deaths. CTCL is usually seen in older
adults; the median age at diagnosis is 55–60 years. It
strikes twice as many men as women. The average life
expectancy at diagnosis is 7–10 years, even without
treatment.

Causes and symptoms
The cause of CTCL is unknown. Exposure to
chemicals or pesticides has been suggested; however,
the most recent study on the subject failed to show a
connection between exposure and development of the
disease. The ability to isolate various viruses from cell
lines grown from cells of CTCL patients raises the
question of a viral cause, but studies have been unable
to confirm these suspicions.
The symptoms of CTCL are seen primarily in the
skin, with itchy red patches or plaques and, usually
over time, mushroom-shaped skin tumors. Any part of
the skin can be involved and the extent and distribution of the rash or tumors vary greatly from patient to
patient. The only really universal symptom of the disease is the itch and this symptom is usually what brings
the patient to the doctor for treatment. If the disease
spreads outside of the skin, the symptoms include
swelling of the lymph nodes, usually most severe in
those draining the areas with skin involvement. Spread
to the viscera is most often manifested as disorders
of the lungs, upper digestive tract, central nervous
system, or liver but virtually any organ can be shown
to be involved at autopsy.
Some patients with CTCL develop a leukemic
phase of the disorder known as Sézary syndrome,
which is characterized by the appearance of malignant
T cells in the bloodstream. It is named for the French
dermatologist who first identified the abnormal
T cells.

Diagnosis
Diagnosis of CTCL is often difficult in the early
stages because of its slow progression and ability to
mimic many other benign skin conditions. The early
patches of CTCL resemble eczema, psoriasis, and contact dermatitis. In a further complication, the early
manifestations of the disease can respond favorably
1077

Cutaneous T-cell lymphoma

larvae are found so commonly in soil and sand. The
play habits of children, together with their attraction
to pets, puts them at high risk for hookworm infection
and cutaneous larvae migrans.

Cutaneous T-cell lymphoma

to the topical corticosteroid treatments prescribed for
these skin disorders. This has the unfortunate result of
the disease being missed and the patient remaining
untreated for years. CTCL is most likely discovered
when a physician maintains a suspicion about the
disease, performs multiple skin biopsies, and provides
close follow-up after the initial presentation.
Skin biopsies showing penetration of abnormal
cells into the epidermal tissue are necessary to make
a firm diagnosis of CTCL. Several molecular studies
can also help support the diagnosis. The first looks at
the cellular proteins seen on the surface of the abnormal cells. Many cases of CTCL show the retention of
the CD4+ protein, but the loss of other proteins
usually seen on the surface of mature CD4+ cells,
such as Leu-8 or Leu-9. The abnormal cells also
show unusual rearrangements at the genetic level for
the gene that encodes the T-cell receptors. These rearrangements can be identified using Southern blot analysis. The information from the molecular tests,
combined with the presence of abnormal cells in the
epidermis, strongly supports the CTCL diagnosis.

Treatment
Treatment of CTCL depends on the stage of the
disease. The current staging of this disease was first
presented at the International Consensus Conference
on CTCL in 1997. The staging attempts to show the
complex interaction between the various outward
symptoms of the disease and prognosis. The system
has seven clinical stages based on skin involvement
(tumor=T), lymph node involvement (LN), and presence of visceral metastases (M).
The first stage, IA, is characterized by plaques
covering less than 10% of the body (T1) and no visceral involvement (M0). Lymph node condition at this
stage can be uninvolved, reactive to the skin disease, or
dermatopathic (biopsies showing CTCL involvement)
but not enlarged (LN0-2). The shorthand expression
of this stage is therefore T1, LN0-2, M0. The next
stage, IB, differs from IA in that greater than 10% of
the body is covered by plaques (T2, LN0-2, M0).
Stage IIA occurs with any amount of plaques in
addition to the ability to palpate the lymph node
and the lymph uninvolved, reactive, or dermatopathic
(T1-2, LN0-2, M0).
Treatments applied to the skin are preferred for
patients having these preliminary stages of the disease,
commonly topical chemotherapy with mechlorethamine
hydrochloride (nitrogen mustard) or phototherapy of
psoralen plus ultraviolet A (PUVA). Topical chemotherapy involves application to the skin of nitrogen
1078

mustard, an alkylating agent, in a concentration of 10–
20 mg/dL in an aqueous or ointment base. Treatment
of affected skin is suggested at a minimum and application over the entire skin surface is often recommended.
Care needs to be taken that coverage of involved skin is
adequate, as patients who self-apply the drug often
cannot reach all affected areas. The most common
side effect is skin hypersensitivity to the drug. Nearly
all patients respond favorably to this treatment, with a
32–61% complete response rate, based on amount of
skin involvement. Unfortunately, only 10–15% of
patients maintain a complete response rate after discontinuing the treatment.
Phototherapy involves treatment with an orally
administered drug, 8-methyloxypsoralen, that renders
the skin sensitive to long-wave ultraviolet light (UVA),
followed by controlled exposure to the radiation.
During the initial treatment period, which may last
as long as six months, patients are treated two to
three times weekly. This is reduced to about once
monthly after initial clearing of the lesions. Redness
of the skin and blistering are the most common side
effects of the treatment and are much more common in
patients presenting with overall skin redness, or erythroderma, so lower intensities of light are usually
used in this case. About 50% of all patients experience
complete clearance with this treatment. Some patients
with very fair skin and limited skin involvement can
successfully treat themselves at home with special
lamps and no psoralen.
The next stage, IIB, involves one or more cutaneous tumors, in combination with absent or present
palpable lymph nodes, lymph uninvolved, reactive, or
dermatopathic, and no visceral involvement (T3,
LN0-2, M0). Stage III is characterized by erythroderma, an abnormal redness over widespread areas
of the skin (T4, LN0-2, M0).
For more extensive disease, radiation therapy is an
effective treatment option. It is generally used after the
topical treatments have proven ineffective. Individual
plaques or tumors can be treated using electrons,
orthovoltage x rays, or megavoltage photons with
exposure in the range of 15 to 25 Gy. Photon therapy
has proven particularly useful once the lymph nodes
are involved. Another possibility is total-skin electron
beam therapy (TSEB), although the availability of this
treatment method is limited. It involves irradiation of
the entire body with energized electrons. Side effects of
this treatment include loss of finger and toe nails,
acute redness of the skin, and inability to sweat for
about six to 12 months after therapy. Almost all
patients respond favorably to radiation treatment
and any reoccurrence is usually much less severe.
GALE ENCYCLOPEDIA OF MEDICINE

The final two stages of the disease are IVA and
IVB. IVA presents as any amount of skin involvement,
absent or present palpable lymph nodes, no visceral
involvement, and lymph that contains large clusters of
convoluted cells or obliterated nodes (T1-4, LN3-4).
IVB differs in the addition of palpable lymph nodes
and visceral involvement (T1-4, LN3-4, M1). All of
the treatment methods described above are appropriate for the final two stages of the disease.
A newer drug that has been used to treat CTCL is
bexarotene, a topical gel that is a synthetic retinoid
analog. Bexarotene has been shown to be effective in
clinical trials for stage IA or IB CTCL, and has fewer
side effects than topical nitrogen mustard or electron
beam radiotherapy. Another team of researchers at
the University of Pennsylvania reported in 2003 that
bexarotene combined with psoralen and UVA therapy
is also effective in treating patients with advanced
CTCL.
A treatment for advanced CTCL that is considered experimental as of mid-2003 is alemtuzumab, a
monoclonal antibody. A Swedish study of 22 patients
with advanced CTCL and Sézary syndrome found
that alemtuzumab relieved symptoms in 55% of
patients, with 32% in complete remission and 23% in
partial remission.

Alternative treatment
Itching of the skin is one of the most troublesome
symptoms of CTCL. One alternative treatment for
itchiness is the application of a brewed solution of
chickweed that is applied to the skin using cloth compresses. Another suggested topical application is a
mixture of vitamin E, vitamin A, unflavored yogurt,
honey, and zinc oxide. Evening primrose oil applied
topically is also claimed to reduce itch and promote
healing.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Alkylating agent—A chemical that alters the composition of the genetic material of rapidly dividing
cells, such as cancer cells, causing selective cell
death; used as a topical chemotherapeutic agent to
treat CTCL.
Cutaneous—Pertaining to the skin.
Erythroderma—An abnormal reddening of the
entire skin surface.
Monoclonal antibody—An antibody produced by
the identical offspring of a single cloned antibodyproducing cell.
Mycosis fungoides—Another name for cutaneous
T-cell lymphoma.
Sézary syndrome—A leukemic phase of CTCL that
develops in some patients, characterized by the
appearance of malignant T cells in the peripheral
blood and sometimes in the lymph nodes. The
syndrome is named for Alfred Sézary (18801956), a French dermatologist.
T-helper cells—A cellular component of the
immune system that plays a major role in ridding
the body of bacteria and viruses, characterized
by the presence of the CD4 protein on its surface;
the type of cell that divides uncontrollable with
CTCL.
Total-skin electron beam therapy—A method of
radiation therapy used to treat CTCL that involves
bombarding the entire body surface with highenergy electrons.

Prognosis
The prognosis for CTCL is dependent on the
stage of the disease. Prognosis is very good if the
disease has only progressed to Stage IA, with a
mean survival of 20 or more years. At this point, the
disease is a very low mortality risk to the patient, with
most deaths occurring to persons in this group unrelated to CTCL. For patients diagnosed at stages IB
and IIA, the median survival is about 12 years. The
disease in both of these stages involves intermediate
risk to the patient. Patients in stage III and IVA have
a mean life expectancy of about five years. At these
later stages, the disease is high risk, with most deaths
occurring by infection due to the depleted immune
system of the later-stage patient. Once a patient
has reached stage IVB, the mean life expectancy is
one year.
1079

Cutaneous T-cell lymphoma

Combination of different types of treatments is a
very common approach to the management of CTCL.
Topical nitrogen mustard or PUVA is often used after
completion of radiation treatment to prolong the
effects. The addition of genetically engineered interferon to PUVA therapy significantly increases the
percentage of patients showing a complete response.
Furthermore, although treatments using chemotherapy drugs alone, such as deoxycofomycin or etretinate, have been disappointing for CTCL, combining
these drugs with interferon has shown promising
results. Interferon has also been combined with
retinoid treatments, although the mechanism of action
of retinoids (Vitamin A analogues) against CTCL is
unknown.

Cutis laxa

Prevention
Studies have been unable to link CTCL to any
environmental or genetic factors as of 2003, so prevention at this time is not possible.

4-CANCER or (800) 332-8615 (TTY). <http://
www.nci.nih.gov>.

Michelle Johnson, M.S., J.D.
Rebecca J. Frey, PhD

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Lymphomas: Mycosis Fungoides.’’ Section 11,
Chapter 139 In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Hoppe, Richard T. ‘‘Mycosis Fungoides and Other
Cutanous Lymphomas.’’ In The Lymphomas, edited by
George P. Canellos, et al. Philadelphia: W.B. Saunders
Co., 1999.
Wilson, Lynn D., et al. ‘‘Cutaneous T-Cell Lymphomas.’’ In
Cancer Principles & Practice of Oncology, edited by
Vincent T. DeVita, et al. Philadelphia: Lippincott
Williams & Wilkins, 2001.
PERIODICALS

Dawe, R. S. ‘‘Ultraviolet A1 Phototherapy.’’ British Journal
of Dermatology 148 (April 2003): 626–637.
Elmer, Kathleen B., and Rita M. George. ‘‘Cutaneous
T-Cell Lymphoma Presenting as Benign Dermatoses.’’
American Family Physician 59 (May 1999): 2809–2815.
Kari, L., A. Loboda, M. Nebozhyn, et al. ‘‘Classification
and Prediction of Survival in Patients with the
Leukemic Phase of Cutaneous T Cell Lymphoma.’’
Journal of Experimental Medicine 197 (June 2, 2003):
1477–1488.
Lundin, J., H. Hagberg, R. Repp, et al. ‘‘Phase 2 Study of
Alemtuzumab (Anti-CD52 Monoclonal Antibody) in
Patients with Advanced Mycosis Fungoides/Sézary
Syndrome.’’ Blood 101 (June 1, 2003): 4267–4272.
Martin, A. G. ‘‘Bexarotene Gel: A New Skin-Directed
Treatment Option for Cutaneous T-Cell Lymphomas.’’
Journal of Drugs in Dermatology 2 (April 2003):
155–167.
McGinnis, K. S., M. Shapiro, C. C. Vittorio, et al. ‘‘Psoralen
plus Long-Wave UV-A (PUVA) and Bexarotene
Therapy: An Effective and Synergistic Combined
Adjunct to Therapy for Patients with Advanced
Cutaneous T-Cell Lymphoma.’’ Archives of
Dermatology 139 (June 2003): 771–775.
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800) ACS-2345.
National Cancer Institute (NCI). NCI Public Inquiries
Office, Suite 3036A, 6116 Executive Boulevard,
MSC8332, Bethesda, MD 20892-8322. (800)
1080

I Cutis laxa
Definition
Cutis laxa (Latin for loose or lax skin) is a connective tissue disorder in which the skin lacks elasticity
and hangs in loose folds.

Description
Cutis laxa is extremely rare; less than a few hundred cases worldwide have been described.
The several forms of cutis laxa are divided into
primary cutis laxa, which is present from birth and is
hereditary, secondary cutis laxa, which arises later in
life and may be hereditary, and acquired cutis laxa,
which arises later in life and is not hereditary. Loose
skin, the primary and most obvious symptom of these
diseases, is caused by underlying defects in connective
tissue structure, which also cause more serious internal
problems in vocal cords, bones, cartilage, blood vessels, bladder, kidney, digestive system, and lungs. The
loose skin is particularly obvious on the face, and
children with the disorder look sad or mournful.
There are four genetic forms of the disease: sexlinked, autosomal dominant, and two types of autosomal recessive inheritance. The recessive forms are
the most common and are usually more severe than
the other forms.

Causes and Symptoms
Sex-linked cutis laxa is caused by a defective gene
on the X chromosome. In addition to loose skin, its
symptoms are mild mental retardation, loose joints,
bone abnormalities (like hooked nose, pigeon breast,
and funnel breast), frequent loose stools, urinary tract
blockages, and deficiencies in lysyl oxidase, an enzyme
required for the formation of properly functioning
connective tissue. (But the defective gene does not
code for lysyl oxidase.)
Autosomal dominant cutis laxa is caused by
a defective gene carried on an autosomal (not sexlinked) chromosome. Its symptoms are loose, hanging
GALE ENCYCLOPEDIA OF MEDICINE

Autosomal recessive cutis laxa type 1 is caused
by a defective gene on chromosome 5. Symptoms
include emphysema; diverticula in the esophagus, duodenum, and bladder; lax and dislocated joints; tortuous arteries; hernias; lysyl oxidase deficiencies; and
retarded growth.
Autosomal recessive cutis laxa type 2 is also inherited as a recessive trait. In addition to the loose skin,
this form of the disease is characterized by bone
abnormalities, the delayed joining of the cranial
(skull) bones, hip dislocation, curvature of the spine,
flat feet, and excessive tooth decay.
Acquired cutis laxa tends to follow (and may be
caused by) severe illness characterized by fever,
inflammation, and a severe skin rash (erythema multiforme); an injury to the nerves that control blood
vessel dilation and contraction; or an autoimmune
condition.

Diagnosis
The signs of cutis laxa are very obvious, and it is
usually easy to diagnose by examining the skin. The
determination of which form of cutis laxa is present is
aided by information about the associated symptoms
and by family histories.

Treatment
There is no effective cure for any of these disorders. Complications are treated by appropriate specialists, for example, cardiologists, gastroenterologists,
rheumatologists, and dermatologists. Plastic surgery
can be helpful for cosmetic purposes, but the skin may
become loose again.

Prognosis
The prognosis for cutis laxa varies with the form
of the disorder. The effects may be relatively mild with
individuals living a fairly normal, full life, or the disease may be fatal.

Prevention
The inherited forms of cutis laxa are genetically
determined and are not currently preventable. Genetic
counseling can be helpful for anyone with a family
history of cutis laxa. The cause of acquired cutis laxa
is not known, so no preventive measures can be taken.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Autosomal—Refers to the 22 pairs (in humans)
of chromosomes not involved with sex
determination.
Connective tissue—Tissue that supports and
binds other tissue; much of it occurs outside
of cells (extra-cellular) and consists of fibrous
webs of the polymers, elastin and collagen.
Cutis laxa is associated with defects in these
fibers.
Diverticula—Pouches in the walls of organs.
Dominant trait—A genetic trait where one copy of
the gene is sufficient to yield an outward display of
the trait; dominant genes mask the presence
of recessive genes; dominant traits can be inherited
from only one parent.
Duodenum—The uppermost part of the small
intestine, about 10 in (25 cm) long.
Esophagus — The tube connecting the throat to the
stomach, about 10 in (25 cm) long.
Funnel breast (also known as pectus excavatum)—
A condition where there is a hollow depression in
the lower part of the chest.
Gene—A portion of a DNA molecule that either
codes for a protein or RNA molecule or has a
regulatory function.
Lysyl oxidase—An enzyme required for the
crosslinking of elastin and collagen molecules
to form properly functioning connective tissue;
present in relatively low levels in at least some
forms of cutis laxa.
Pigeon breast (also known as pectus carinatum)—
A chest shape with a central projection resembling
the keel of a boat.
Recessive trait—An inherited trait that is outwardly obvious only when two copies of the
gene for that trait are present; an individual
displaying a recessive trait must have inherited
one copy of the defective gene from each
parent.
Sex-linked—Refers to genes or traits carried on one
of the sex chromosomes, usually the X.
Tortuous arteries—Arteries with many bends and
twists.
X chromosome—One of the two types of sex chromosomes; females have two X chromosomes,
while males have one X chromosome and one
Y chromosome.

1081

Cutis laxa

skin, missing elastic fibers, premature aging, and pulmonary emphysema. Only a few families are known
with cutis laxa inherited as a dominant trait.

Cyanosis

Resources

KEY TERMS

ORGANIZATIONS

British Coalition of Heritable Disorders of Connective Tissue.
Rochester House, 5 Aldershot Road, Fleet, Hampshire
GU13 9NG, United Kingdom. (012) 52-810472.
OTHER

OMIM Homepage, Online Mendelian Inheritance in Man.
<http://www.ncbi.nlm.nih.gov/Omim>.

Lorraine Lica, PhD

Hemoglobin—A colored substance (pigment) in
the blood that carries oxygen to tissues and gives
blood its red color.
Respiratory distress syndrome—Also known as
hyaline membrane disease, this is a condition of
premature infants in which the lungs are imperfectly expanded due to a lack of a substance on
the lungs that reduces tension.

Cuts see Wounds
CVA see Stroke
CVS see Chorionic villus sampling; Cyclic
vomiting syndrome

I Cyanosis
Definition
Cyanosis is a physical sign causing bluish discoloration of the skin and mucous membranes. Cyanosis
is caused by a lack of oxygen in the blood. Cyanosis is
associated with cold temperatures, heart failure, lung
diseases, and smothering. It is seen in infants at birth
as a result of heart defects, respiratory distress syndrome, or lung and breathing problems.

Description
Blood contains a red pigment (hemoglobin) in its
red blood cells. Hemoglobin picks up oxygen from the
lungs, then circulates it through arteries and releases it
to cells through tiny capillaries. After giving up its
oxygen, blood circulates back to the lungs through
capillaries and veins. Hemoglobin, as well as blood,
is bright red when it contains oxygen, but appears dark
or ‘‘bluish’’ after it gives up oxygen.
The blue discoloration of cyanosis is seen most readily in the beds of the fingernails and toenails, and on the
lips and tongue. It often appears transiently as a result of
slowed blood flow through the skin due to the cold. As
such, it is not a serious symptom. However, in other cases
cyanosis is a serious symptom of underlying disease.

Causes and symptoms
The blue color of the skin and mucous membranes
is caused by a lack of oxygen in the blood. Low blood
oxygen may be caused by poor blood circulation, or
1082

This elderly woman’s lips turned purple due to central cyanosis, a condition most commonly due to slow blood circulation, leading to a bluish skin coloration. (Photo Researchers,
Inc. Reproduced by permission.)

heart or breathing problems. It can also be caused by
being in a low-oxygen environment or by carbon monoxide poisoning. More rarely, cyanosis can be present at
birth as a sign of congenital heart disease, in which some
of the blood is not pumped to the lungs where oxygen
would make the blood a bright red color. Instead, the
blood goes to the rest of the body and remains unoxygenated. Cyanosis also may be caused by poisoning
from chemicals, drugs, or contaminated food and water.
Other signs of low blood oxygen may accompany
cyanosis, including feeling lightheaded or fainting.

Treatment
Treatment of the underlying disease can restore
proper color to the skin.

Prognosis
If the underlying condition (such as heart or lung
disease) can be properly treated, the skin will return to
its normal shade.
GALE ENCYCLOPEDIA OF MEDICINE

CVS has four distinct stages or phases:

BOOKS



Prodrome. A prodrome is a warning symptom (or
group of symptoms) that appears just before an acute
attack of an illness. Patients with CVS often feel pain
in the abdomen a few minutes or hours before the
vomiting starts. Adults with CVS often have anxiety
or panic attacks as a prodrome.



Episode phase. During this phase, the patient is
actively nauseated and vomiting. He or she may
also feel drowsy or exhausted.



Recovery phase.



Symptom-free interval.

Carolson, Karen J., Stephanie A. Eisenstat, and Terra
Ziporyn. The Harvard Guide to Women’s Health.
Cambridge, MA: Harvard University Press, 1996.

Carol A. Turkington

I Cyclic vomiting syndrome
Definition
Cyclic vomiting syndrome (CVS) is a rare idiopathic disorder characterized by recurring periods of
vomiting in an otherwise normal child or adult. It was
first described in 1882 by a physician named Gee. CVS
is sometimes called abdominal migraine because it
may be caused by some of the same mechanisms in
the central nervous system that cause migraine
headaches.

Description
Children in the pre-school or early school years
are most susceptible to CVS, although it can appear
anywhere from infancy to adulthood. One doctor
reports that 43 of the 233 patients with CVS that he
has treated were adults when their symptoms began.
The average age of patients at onset is 5.2 years, but
CVS has been diagnosed in patients as old as 73. This
disorder was identified over a century ago, but its
cause is still unknown. Episodes can be triggered by
emotional stress or infections (particularly sinusitis),
can last hours or days, and can return at any time.
Abdominal pain is a frequent feature.
CVS appears to affect all races equally. The
female:male ratio has been reported as 11:9.

Diagnosis
The most important and difficult aspect of CVS is
to be sure there is not an acute and life-threatening
event in progress. So many different diseases can cause
vomiting—from bowel obstruction to epilepsy—that
an accurate and timely diagnosis is critical. Because
there is no way to prove the diagnosis of CVS, the
physician must instead disprove every other diagnosis.
This process, which is known as a diagnosis of exclusion, can be tedious, expensive, exhausting, and
involve almost every system in the body. The first
episode may be diagnosed as a stomach flu when
nothing more serious turns up. Only after several episodes and several fruitless searches for a cause will a
physician normally consider the diagnosis of CVS.
A careful history-taking is critical to making the
correct diagnosis of CVS. A family history of
migraine, particularly on the mother’s side of the
family, should alert the doctor to the possibility that
the patient has CVS.
In some cases, the doctor may refer the patient to
a psychiatrist for evaluation in order to rule out anxiety disorders or an eating disorder.

Treatment
Causes and symptoms
The cause of CVS is still a mystery. Similarities to
migraine suggest a common cause, but as yet no firm
evidence has surfaced. It is known, however, that 82%
of patients with CVS have a family history of migraine
compared to 14% of control subjects. Patients can
usually identify some factor that precedes an attack.
Vomiting can be protracted and lead to such complications as dehydration, chemical imbalances, and
tearing, burning, and bleeding of the esophagus
(swallowing tube). Between attacks, there is no sign
of any illness.
GALE ENCYCLOPEDIA OF MEDICINE

Several different medications have given good
results in small trials. The antimigraine drugs amitriptyline and cyproheptadine performed well for one
study group. Propranolol is sometimes effective, and
erythromycin helped several patients in one study, not
because it is an antibiotic but because it irritates the
stomach and encourages it to move its contents
forward instead of in reverse.
Another medication that has been reported to be
successful in treating children with CVS is dexmedetomidine (Precedex), a drug originally developed to
sedate patients on respirators in intensive care
1083

Cyclic vomiting syndrome

Resources

Cyclosporiasis

KEY TERMS
Abdominal migraine—Another term that is sometimes used for CVS.
Idiopathic—Of unknown cause or spontaneous
origin. CVS is sometimes called an idiopathic disorder because its cause(s) are still not known.
Prodrome—A symptom or group of symptoms that
appears shortly before an acute attack of illness.
The term comes from a Greek word that means
‘‘running ahead of.’’

settings. The researchers found that dexmedetomidine relieved the anxiety as well as the nausea associated with CVS.

Sundaram, Shikha, MD, and B. Uk Li, MD. ‘‘Cyclic
Vomiting Syndrome.’’ eMedicine August 10, 2002.
<http://www.emedicine.com/ped/topic2910.htm>.
ORGANIZATIONS

Cyclic Vomiting Syndrome Association in the United States
and Canada (CVSA—USA/Canada). 3585 Cedar Hill
Road, NW, Canal Winchester, OH 43110. (614)
837-2586. <http://www.cvsaonline.org>.
National Organization for Rare Disorders, Inc. (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813.
(800) 999-6673 or (203) 744-0100. <http://
www.rarediseases.org>.
OTHER

National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK). Cyclic Vomiting Syndrome. NIH
Publication No. 01-4548. Bethesda, MD: NIDDK,
2001. <http://digestive.niddk.nih.gov/ddiseases/pubs/
cvs/index.htm>.

J. Ricker Polsdorfer, MD
Rebecca J. Frey, PhD

Alternative treatment
Constitutional homeopathic medicine can work
well in treating CVS because it addresses rebalancing
the whole person, not just the symptoms.
According to a 1999 article in the journal Medical
Acupuncture, weekly outpatient acupuncture treatments are also helpful to some children with CVS.

Cyclobenzaprine see Muscle relaxants
Cyclophospha see Anticancer drugs
Cyclospora infection see Cyclosporiasis

Prognosis
The disease may go on for many years without a
change in pattern. If the acute complications of prolonged vomiting can be successfully prevented or managed, most patients can lead normal lives between
episodes. Medications may ease the symptoms during
attacks.
Resources
PERIODICALS

Fleisher, David R., MD. ‘‘Cyclic Vomiting Syndrome in
Adults.’’ Code ‘‘V’’: The Official Newsletter of the
CVSA—USA/Canada 11 (Spring 2003): 1–3.
Khasawinah, T. A., A. Ramirez, J. W. Berkenbosch, and J.
D. Tobias. ‘‘Preliminary Experience with
Dexmedetomidine in the Treatment of Cyclic Vomiting
Syndrome.’’ American Journal of Therapeutics 10 (JulyAugust 2003): 303–307.
Li, B. U., and L. Misiewicz. ‘‘Cyclic Vomiting Syndrome: A
Brain-Gut Disorder.’’ Gastroenterology Clinics of North
America 32 (September 2003): 997–1019.
Lin, Yuan-Chi, MD, and Brenda Golianu, MD.
‘‘Acupuncture as Complementary Treatment for Cyclic
Vomiting Syndrome.’’ Medical Acupuncture 13 (March
1999): 1–4.
1084

I Cyclosporiasis
Definition
Cyclosporiasis refers to infection by the sporeforming protozoan known as Cyclospora. Protozoa
are a group of parasites that infect the human intestine. Parasites are organisms that live in another body,
called the host, and get food and liquids from that
host. This parasite is a member of the group of protozoa known as coccidia, to which Cryptosporidia also
belongs. This group of parasites infects the human
intestine, and causes chronic recurrent infections in
those with altered immunity or AIDS. Even in people
with normal immune function, Cyclopsora can cause
prolonged bouts of diarrhea and other gastrointestinal
symptoms.

Description
Until recently, Cyclospora was considered to be a
form of algae. The parasite causes a common form of
waterborne infectious diarrhea throughout the world.
Just how the parasite gets into water sources is not yet
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Symptoms begin after an incubation period of
about a day or so following ingestion of cysts. A
brief period of flu-like illness characterized by weakness and low-grade fever is followed by watery diarrhea, nausea, loss of appetite, and muscle aches. In
some patients, symptoms may wax and wane for
weeks, and there are those in whom nausea and burping may predominate. It is also believed that infection
can occur without any symptoms at all.
In patients with abnormal immunity (immunocompromised patients), such as those with AIDS and
cancer, prolonged diarrhea and severe weight loss
often become a major problem. The bile ducts are
also susceptible to infection in AIDS patients.

Diagnosis
The disease should be suspected in anyone with a
history of prolonged or recurrent diarrhea. The parasite is identified either by staining stool specimens or
by applying certain fluorescent ultraviolet techniques
to find the characteristic cysts. Biopsy of an infected
organ such as the intestine through an endoscope is
another way to make the diagnosis.

Treatment
The first aim of treatment as with any severe
diarrheal illness is to avoid dehydration and malnutrition. Oral Rehydration Solution (ORS) or intravenous
fluids are sometimes needed. Medications used to treat
diarrhea by decreasing intestinal motility, such as
loperamide or diphenoxylate are also useful, but
should only be used with the advice of a physician.
The use of the medication, trimethoprimsulfamethoxazole (Bactrim) for one week can be
successful in treating intestinal infections and prevents
relapse in those with a normal immune system. The
same medicine can be prescribed to treat infections of
both the intestine or bile ducts in immunocompromised individuals, but maintenance or continuous
treatment is often needed.

Prognosis
The outlook is quite good for individuals in whom
a diagnosis is made. Even without treatment, symptoms usually do not last much more than a month
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anti-motility medications—Medications such as
loperamide (sold as Imodium), dephenoxylate
(sold as Lomotil), or medications containing
codeine or narcotics that decrease the ability of
the intestine to contract. This can worsen the condition of a patient with dysentery or colitis.
Cyst—A protective sac that includes either fluid or
the cell of an organism. The cyst enables many
organisms to survive in the environment for long
periods of time without need for food or water.
Immunocompromised—A change or alteration of
the immune system that normally serves to fight off
infections other illnesses. This can involve changes in
antibodies that the body produces (hygogammaglobulinemia), or a defect in the cells that partake in the
immune response. Diseases such as AIDS and cancer
exhibit changes in the body’s natural immunity.
Oral Rehydration Solution (ORS)—A liquid preparation developed by the World Health
Organization that can decrease fluid loss in persons
with diarrhea. Originally developed to be prepared
with materials available in the home, commercial
preparations have recently come into use.
Parasite—An organism that lives on or in another
and takes nourishment (food and fluids) from that
organism.
Protozoa—Group of extremely small single cell
(unicellular) or acellular organisms that are found
in moist soil or water. They tend to exist as parasites, living off other life forms.
Spore—A resistant form of certain species of bacteria, protozoa, and other organisms.

except in cases with altered immunity. Fortunately,
treatment is usually successful even in those patients.

Prevention
Aside from a waterborne source as the origin of
infection, little else is known about how the parasite is
transmitted. Therefore, little can be done regarding
prevention, except to maintain proper hand washing
techniques and hygiene.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
1085

Cyclosporiasis

clear. It is known that ingestion of small cysts in contaminated water leads to disease.

Cystectomy

OTHER

‘‘Cyclospora.’’ Centers for Disease Control. <http://
www.cdc.gov/ncidod/diseases/cyclospo/
cyclohp.htm>.

David Kaminstein, MD

Cyclosporine see Immunosuppressant drugs

I Cystectomy
Definition
Cystectomy is a surgical procedure to remove the
bladder.

Purpose
Cystectomy is performed to treat cancer of the
bladder. Radiation and chemotherapy are also used
to treat bladder cancer. Surgery is used to remove
cancer when it is in the muscle of the bladder.

Precautions
Cystectomy is an aggressive treatment that may
not be appropriate for patients with superficial tumors
that respond to more conservative treatment.

Description
Cystectomy is a major surgical operation. The
patient is placed under general anesthesia. An incision
is made across the lower abdomen. The ureters are
located, tied and cut. The ureters connect the kidneys
to the bladder. Cutting them frees the bladder for
removal. The bladder and associated organs are
removed. In men the prostate is removed with the
bladder. In women, the uterus, fallopian tubes, ovaries, and part of the vagina are removed with the bladder. The bladder collects urine from the kidneys for
excretion at a later time. Since the bladder is removed,
a new method must be created to remove the urine. A
small piece of the small intestine is removed, cleaned,
and tied at one end to form a tube. The other end is
used to form a stoma, an opening through the abdominal wall to the outside. The ureters are then connected
to the tube. Urine produced by the kidneys now flows
down the ureters, into the tube, and through the
stoma. The patient wears a bag to collect the urine.
1086

KEY TERMS
Ureters—Tubes that connect the kidneys to the
bladder. Urine produced by the kidneys passes
through the ureters to the bladder.

Preparation
The medical team will discuss the procedure and
tell the patient where the stoma will appear and what it
will look like. The patient receives instruction on caring for a stoma and bag. Counseling may be initiated.
A period of fasting and an enema may be required.

Aftercare
After the operation, the patient is given fluidbased nutrition until the intestines being to function
normally again. Antibiotics are given to prevent infection of the incision sites. The nature of the organs
removed mean that there will be major lifestyle
changes for the person undergoing the operation.
Men will become impotent because nerves controlling
penile erection are cut during removal of the bladder.
In women, infertility is a consequence because the
ovaries and uterus are removed. However, most
women who undergo cystectomy are postmenopausal
and past their childbearing years.
Both men and women are fitted with an external
bag that connects to the stoma and collects the urine.
The bag is generally worn around the waist under the
clothing. It takes a period of adjustment to get used to
wearing the bag. Because there is no bladder, urine is
excreted as it is produced, essentially continuously.
The stoma must be treated properly to ensure that it
does not become infected or blocked. Patients must be
trained to care for their stoma. Often there is a period
of psychological adjustment to the major change in life
style created by the stoma and bag. Patients should be
prepared for this by discussion with their physician.

Risks
As with any major surgery, there is a risk of infection; in this case infection of the intestine is especially
dangerous as it can lead to peritonitis (inflammation of
the membrane lining the abdomen).

Normal results
The bladder is successfully removed and a stoma
created. Intestinal function returns to normal and the
GALE ENCYCLOPEDIA OF MEDICINE

Abnormal results

are developed, and it is estimated that a person born in
1998 with CF has a median expected life span of
40 years.

Causes and symptoms

The patient develops an infection at the incision
site. The patient does not make a successful psychological adjustment to the long term consequences of
impotence and urinary diversion. In some women, the
vagina is constricted, which may require a secondary
procedure.
Resources
BOOKS

Berkow, Robert, editor. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

John T. Lohr, PhD

I Cystic fibrosis
Definition
Cystic fibrosis (CF) is an inherited disease that
affects the lungs, digestive system, sweat glands, and
male fertility. Its name derives from the fibrous scar
tissue that develops in the pancreas, one of the principal organs affected by the disease.

Description
Cystic fibrosis affects the body’s ability to move
salt and water in and out of cells. This defect causes the
lungs and pancreas to secrete thick mucus, blocking
passageways and preventing proper function.
CF affects approximately 30,000 children and
young adults in the United States, and about 3,000
babies are born with CF every year. CF primarily
affects people of white northern-European descent;
rates are much lower in non-white populations.
Many of the symptoms of CF can be treated with
drugs or nutritional supplements. Close attention to
and prompt treatment of respiratory and digestive
complications have dramatically increased the
expected life span of a person with CF. While several
decades ago most children with CF died by age two,
today about half of all people with CF live past age 31.
That median age is expected to grow as new treatments
GALE ENCYCLOPEDIA OF MEDICINE

Causes
Cystic fibrosis is a genetic disease, meaning it is
caused by a defect in the person’s genes. Genes, found
in the nucleus of all the body’s cells, control cell function by serving as the blueprint for the production of
proteins. Proteins carry out a wide variety of functions
within cells. The gene that, when defective, causes CF
is called the CFTR gene, which stands for cystic fibrosis transmembrane conductance regulator. A simple
defect in this gene leads to all the consequences of CF.
There are over 500 known defects in the CFTR gene
that can cause CF. However, 70% of all people with a
defective CFTR gene have the same defect, known as
delta-F508.
Much as sentences are composed of long strings of
words, each made of letters, genes can be thought of as
long strings of chemical words, each made of chemical
letters, called nucleotides. Just as a sentence can be
changed by rearranging its letters, genes can be
mutated, or changed, by changes in the sequence of
their nucleotide letters. The gene defects in CF are
called point mutations, meaning that the gene is
mutated only at one small spot along its length. In
other words, the delta-F508 mutation is a loss of one
‘‘letter’’ out of thousands within the CFTR gene. As a
result, the CFTR protein made from its blueprint is
made incorrectly, and cannot perform its function
properly.
The CFTR protein helps to produce mucus.
Mucus is a complex mixture of salts, water, sugars,
and proteins that cleanses, lubricates, and protects
many passageways in the body, including those in
the lungs and pancreas. The role of the CFTR protein
is to allow chloride ions to exit the mucus-producing
cells. When the chloride ions leave these cells, water
follows, thinning the mucus. In this way, the CFTR
protein helps to keep mucus from becoming thick and
sluggish, thus allowing the mucus to be moved steadily
along the passageways to aid in cleansing.
In CF, the CFTR protein cannot allow chloride
ions out of the mucus-producing cells. With less chloride leaving, less water leaves, and the mucus becomes
thick and sticky. It can no longer move freely through
the passageways, so they become clogged. In the pancreas, clogged passageways prevent secretion of digestive enzymes into the intestine, causing serious
1087

Cystic fibrosis

patient learns proper care of the stoma and bag. He or
she adjusts to lifestyle changes and returns to a normal
routine of work and recreation, some sports excluded.

Cystic fibrosis

D O R O T H Y A N D E R S E N (1901–1963)
Dorothy Andersen was born on May 15, 1901, in
Asheville, North Carolina. She was the only child of
Hans Peter Andersen and the former Mary Louise
Mason. Orphaned as a young adult, Andersen put herself through Saint Johnsbury Academy and Mount
Holyoke College before enrolling in the Johns Hopkins
School of Medicine, from which she received her M.D.
in 1926.

(Library of Congress)

impairment of digestion–especially of fat–which may
lead to malnutrition. Mucus in the lungs may plug the
airways, preventing good air exchange and, ultimately, leading to emphysema. The mucus is also a
rich source of nutrients for bacteria, leading to frequent infections.
INHERITANCE OF CYSTIC FIBROSIS. To understand
the inheritance pattern of CF, it is important to realize
that genes actually have two functions. First, as noted
above, they serve as the blueprint for the production of
proteins. Second, they are the material of inheritance:
parents pass on characteristics to their children by
combining the genes in egg and sperm to make a new
individual.

Each person actually has two copies of each gene,
including the CFTR gene, in each of their body cells.
During sperm and egg production, however, these two
copies separate, so that each sperm or egg contains
only one copy of each gene. When sperm and egg
unite, the newly created cell once again has two copies
of each gene.
The two gene copies may be the same or they may
be slightly different. For the CFTR gene, for instance,
a person may have two normal copies, or one normal
and one mutated copy, or two mutated copies. A
person with two mutated copies will develop cystic
1088

Andersen turned instead to medical research as a
pathologist at Babies Hospital of the ColumbiaPresbyterian Medical Center in New York City, where
she stayed for more than 20 years, eventually becoming
chief of pathology in 1952. Andersen is probably best
known for her discovery of cystic fibrosis in 1935. That
discovery came about during the postmortem examination of a child who had supposedly died of celiac disease,
a nutritional disorder. She searched for similar cases in
the autopsy files and in medical literature, eventually
realizing that she had found a disease that had never
been described and to which she gave the name cystic
fibrosis.

fibrosis. A person with one mutated copy is said to
be a carrier. A carrier will not have symptoms of CF,
but can pass on the mutated CFTR gene to his/her
children.
When two carriers have children, they have a one
in four chance of having a child with CF each time
they conceive. They have a two in four chance of
having a child who is a carrier, and a one in four
chance of having a child with two normal CFTR
genes.
Approximately one in every 25 Americans of
northern-European descent is a carrier of the mutated
CF gene, while only one in 17,000 African Americans
and one in 30,000 Asian Americans are carriers. Since
carriers are symptom-free, very few people will know
whether or not they are carriers unless there is a family
history of the disease. Two white Americans with no
family history of CF have a one in 2,500 chance of
having a child with CF.
It may seem puzzling that a mutated gene with
such harmful consequences would remain so common;
one might guess that the high mortality of CF would
quickly lead to loss of the mutated gene from the
population. Some researchers now believe the reason
for the persistence of the CF gene is that carriers, those
with only one copy of the gene, are protected from the
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms
The most severe effects of cystic fibrosis are seen
in two body systems: the gastrointestinal (digestive)
system, and the respiratory tract, from the nose to the
lungs. CF also affects the sweat glands and male fertility. Symptoms develop gradually, with gastrointestinal symptoms often the first to appear.
GASTROINTESTINAL SYSTEM. Ten to fifteen percent
of babies who inherit CF have meconium ileus at birth.
Meconium is the first dark stool that a baby passes
after birth; ileus is an obstruction of the digestive tract.
The meconium of a newborn with meconium ileus is
thickened and sticky, due to the presence of thickened
mucus from the intestinal glands. Meconium ileus
causes abdominal swelling and vomiting, and often
requires surgery immediately after birth. Presence of
meconium ileus is considered highly indicative of CF.
Borderline cases may be misdiagnosed, however, and
attributed instead to ‘‘milk allergy.’’

Other abdominal symptoms are caused by the
inability of the pancreas to supply digestive enzymes
to the intestine. During normal digestion, as food
passes from the stomach into the small intestine, it is
mixed with pancreatic secretions which help to break
down the nutrients for absorption. While the intestines
themselves also provide some digestive enzymes, the
pancreas is the major source of enzymes for the digestion of all types of foods, especially fats and proteins.
In CF, thick mucus blocks the pancreatic duct,
which is eventually closed off completely by scar tissue
formation, leading to a condition known as pancreatic
insufficiency. Without pancreatic enzymes, large
amounts of undigested food pass into the large intestine. Bacterial action on this rich food source can
cause gas and abdominal swelling. The large amount
of fat remaining in the feces makes it bulky, oily, and
foul-smelling.
Because nutrients are only poorly digested and
absorbed, the person with CF is often ravenously
hungry, underweight, and shorter than expected for
his age. When CF is not treated for a longer period,
a child may develop symptoms of malnutrition,
GALE ENCYCLOPEDIA OF MEDICINE

including anemia, bloating, and, paradoxically, appetite loss.
Diabetes becomes increasingly likely as a person
with CF ages. Scarring of the pancreas slowly destroys
those pancreatic cells which produce insulin, producing type I, or insulin-dependent diabetes.
Gall stones affect approximately 10% of adults
with CF. Liver problems are less common, but can
be caused by the buildup of fat within the liver.
Complications of liver enlargement may include internal hemorrhaging, abdominal fluid (ascites), spleen
enlargement, and liver failure.
Other gastrointestinal symptoms can include a
prolapsed rectum, in which part of the rectal lining
protrudes through the anus; intestinal obstruction;
and rarely, intussusception, in which part of the intestinal tube slips over an adjoining part, cutting off blood
supply.
Somewhat less than 10% of people with CF do
not have gastrointestinal symptoms. Most of these
people do not have the delta-F508 mutation, but
rather a different one, which presumably allows at
least some of their CFTR proteins to function normally in the pancreas.
RESPIRATORY
TRACT. The
respiratory tract
includes the nose, the throat, the trachea (or windpipe), the bronchi (which branch off from the trachea
within each lung), the smaller bronchioles, and the
blind sacs called alveoli, in which gas exchange takes
place between air and blood.

Swelling of the sinuses within the nose is common
in people with CF. This usually shows up on x ray, and
may aid the diagnosis of CF. However, this swelling,
called pansinusitis, rarely causes problems, and does
not usually require treatment.
Nasal polyps, or growths, affect about one in five
people with CF. These growths are not cancerous, and
do not require removal unless they become annoying.
While nasal polyps appear in older people without CF,
especially those with allergies, they are rare in children
without CF.
The lungs are the site of the most life-threatening
effects of CF. The production of a thick, sticky mucus
increases the likelihood of infection, decreases the
ability to protect against infection, causes inflammation and swelling, decreases the functional capacity of
the lungs, and may lead to emphysema. People with
CF will live with chronic populations of bacteria in
their lungs, and lung infection is the major cause of
death for those with CF.
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Cystic fibrosis

full effects of cholera, a microorganism that infects the
intestine, causing intense diarrhea and eventual death
by dehydration. It is believed that having one copy of
the CF gene is enough to prevent the full effects of
cholera infection, while not enough to cause the symptoms of CF. This so-called ‘‘heterozygote advantage’’
is seen in some other genetic disorders, including
sickle-cell anemia.

Cystic fibrosis

The bronchioles and bronchi normally produce a
thin, clear mucus that traps foreign particles including
bacteria and viruses. Tiny hair-like projections on the
surface of these passageways slowly sweep the mucus
along, out of the lungs and up the trachea to the
back of the throat, where it may be swallowed or
coughed up. This ‘‘mucociliary escalator’’ is one of
the principal defenses against lung infection.
The thickened mucus of CF prevents easy movement out of the lungs, and increases the irritation and
inflammation of lung tissue. This inflammation swells
the passageways, partially closing them down, further
hampering the movement of mucus. A person with CF
is likely to cough more frequently and more vigorously
as the lungs attempt to clean themselves out.
At the same time, infection becomes more likely
since the mucus is a rich source of nutrients.
Bronchitis, bronchiolitis, and pneumonia are frequent
in CF. The most common infecting organisms are the
bacteria Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa. A small percentage
of people with CF have infections caused by
Burkholderia cepacia, a bacterium which is resistant
to most current antibiotics (Burkholderia cepacia was
formerly known as Pseudomonas cepacia.) The fungus
Aspergillus fumigatus may infect older children and
adults.
The body’s response to infection is to increase
mucus production; white blood cells fighting the infection thicken the mucus even further as they break
down and release their cell contents. These white
blood cells also provoke more inflammation, continuing the downward spiral that marks untreated CF.
As mucus accumulates, it can plug up the smaller
passageways in the lungs, decreasing functional lung
volume. Getting enough air can become difficult;
tiredness, shortness of breath, and intolerance of exercise become more common. Because air passes
obstructions more easily during inhalation than
during exhalation, over time, air becomes trapped in
the smallest chambers of the lungs, the alveoli. As
millions of alveoli gradually expand, the chest takes
on the enlarged, barrel-shaped appearance typical of
emphysema.
For unknown reasons, recurrent respiratory
infections lead to ‘‘digital clubbing,’’ in which the
last joint of the fingers and toes becomes slightly
enlarged.
SWEAT GLANDS. The CFTR protein helps to
regulate the amount of salt in sweat. People with CF
have sweat that is much saltier than normal, and
measuring the saltiness of a person’s sweat is the

1090

most important diagnostic test for CF. Parents may
notice that their infants taste salty when they kiss
them. Excess salt loss is not usually a problem except
during prolonged exercise or heat. While most older
children and adults with CF compensate for this extra
salt loss by eating more salty foods, infants and young
children are in danger of suffering its effects (such as
heat prostration), especially during summer. Heat
prostration is marked by lethargy, weakness, and
loss of appetite, and should be treated as an emergency
condition.
FERTILITY. Ninety-eight percent of men with CF
are sterile, due to complete obstruction or absence of
the vas deferens, the tube carrying sperm out of the
testes. While boys and men with CF form normal
sperm and have normal levels of sex hormones,
sperm are unable to leave the testes, and fertilization
is not possible. Most women with CF are fertile,
though they often have more trouble getting pregnant
than women without CF. In both boys and girls, puberty is often delayed, most likely due to the effects of
poor nutrition or chronic lung infection. Women with
good lung health usually have no problems with pregnancy, while those with ongoing lung infection often
do poorly.

Diagnosis
The decision to test a child for cystic fibrosis may
be triggered by concerns about recurring gastrointestinal or respiratory symptoms, or salty sweat. A child
born with meconium ileus will be tested before leaving
the hospital. Families with a history of CF may wish to
have all children tested, especially if there is a child
who already has the disease. Some hospitals now
require routine screening of newborns for CF.
Sweat test
The sweat test is both the easiest and most accurate test for CF. In this test, a small amount of the
drug pilocarpine is placed on the skin. A very small
electrical current is then applied to the area, which
drives the pilocarpine into the skin. The drug stimulates sweating in the treated area. The sweat is
absorbed onto a piece of filter paper, and is then
analyzed for its salt content. A person with CF will
have salt concentrations that are one-and-one-half
to two times greater than normal. The test can be
done on persons of any age, including newborns,
and its results can be determined within an hour.
Virtually every person who has CF will test positively on it, and virtually everyone who does not
will test negatively.
GALE ENCYCLOPEDIA OF MEDICINE

The discovery of the CFTR gene in 1989 allowed
the development of an accurate genetic test for CF.
Genes from a small blood or tissue sample are analyzed
for specific mutations; presence of two copies of the
mutated gene confirms the diagnosis of CF in all but a
very few cases. However, since there are so many different possible mutations, and since testing for all of
them would be too expensive and time-consuming, a
negative gene test cannot rule out the possibility of CF.
Couples planning a family may decide to have
themselves tested if one or both have a family history
of CF. Prenatal genetic testing is possible through
amniocentesis. Many couples who already have one
child with CF decide to undergo prenatal screening in
subsequent pregnancies, and use the results to determine whether to terminate the pregnancy. Siblings in
these families are also usually tested, both to determine
if they will develop CF, and to determine if they are
carriers, to aid in their own family planning. If the
sibling has no symptoms, determining his carrier status
is often delayed until his teen years or later, when he is
closer to needing the information to make decisions.
Newborn screening
Some states now require screening of newborns
for CF, using a test known as the IRT test. This is a
blood test which measures the level of immunoreactive
trypsinogen, which is generally higher in babies with
CF than those without it. This test gives many false
positive results immediately after birth, and so
requires a second test several weeks later. A second
positive result is usually followed by a sweat test.

Treatment
There is no cure for CF. Treatment has advanced
considerably in the past several decades, increasing
both the life span and the quality of life for most
people affected by CF. Early diagnosis is important
to prevent malnutrition and infection from weakening
the young child. With proper management, many people with CF engage in the full range of school and
sports activities.
Nutrition
People with CF usually require high-calorie diets
and vitamin supplements. Height, weight, and growth
of a person with CF are monitored regularly. Most
people with CF need to take pancreatic enzymes to
supplement or replace the inadequate secretions of the
pancreas. Tablets containing pancreatic enzymes are
GALE ENCYCLOPEDIA OF MEDICINE

taken with every meal; depending on the size of the
tablet and the meal, as many as 20 tablets may be
needed. Because of incomplete absorption even with
pancreatic enzymes, a person with CF needs to take in
about 30% more food than a person without CF.
Low-fat diets are not recommended except in special
circumstances, since fat is a source of both essential
fatty acids and abundant calories.
Some people with CF cannot absorb enough
nutrients from the foods they eat, even with specialized
diets and enzymes. For these people, tube feeding is an
option. Nutrients can be introduced directly into the
stomach through a tube inserted either through the
nose (a nasogastric tube) or through the abdominal
wall (a gastrostomy tube). A jejunostomy tube,
inserted into the small intestine, is also an option.
Tube feeding can provide nutrition at any time,
including at night while the person is sleeping, allowing constant intake of high-quality nutrients. The
feeding tube may be removed during the day, allowing
normal meals to be taken.
Respiratory health
The key to maintaining respiratory health in a
person with CF is regular monitoring and early treatment. Lung function tests are done frequently to track
changes in functional lung volume and respiratory
effort. Sputum samples are analyzed to determine the
types of bacteria present in the lungs. Chest x rays are
usually taken at least once a year. Lung scans, using a
radioactive gas, can show closed off areas not seen on
the x ray. Circulation in the lungs may be monitored
by injection of a radioactive substance into the
bloodstream.
People with CF live with chronic bacterial colonization; that is, their lungs are constantly host to several species of bacteria. Good general health,
especially good nutrition, can keep the immune system
healthy, which decreases the frequency with which
these colonies begin an infection, or attack on the
lung tissue. Exercise is another important way to
maintain health, and people with CF are encouraged
to maintain a program of regular exercise.
In addition, clearing mucus from the lungs helps
to prevent infection; and mucus control is an important aspect of CF management. Postural drainage is
used to allow gravity to aid the mucociliary escalator.
For this technique, the person with CF lies on a tilted
surface with head downward, alternately on the
stomach, back, or side, depending on the section of
lung to be drained. An assistant thumps the rib cage to
help loosen the secretions. A device called a ‘‘flutter’’
1091

Cystic fibrosis

Genetic testing

Cystic fibrosis

offers another way to loosen secretions: it consists of a
stainless steel ball in a tube. When a person exhales
through it, the ball vibrates, sending vibrations back
through the air in the lungs. Some special breathing
techniques may also help clear the lungs.
Several drugs are available to prevent the airways
from becoming clogged with mucus. Bronchodilators
and theophyllines open up the airways; steroids reduce
inflammation; and mucolytics loosen secretions.
Acetylcysteine (Mucomyst) has been used as a mucolytic for many years but is not prescribe frequently
now, while DNase (Pulmozyme) is a newer product
gaining in popularity. DNase breaks down the DNA
from dead white blood cells and bacteria found in
thick mucus.
People with CF may pick up bacteria from other
CF patients. This is especially true of Burkholderia
cepacia, which is not usually found in people without
CF. While the ideal recommendation from a health
standpoint might be to avoid contact with others who
have CF, this is not usually practical (since CF clinics
are a major site of care), nor does it meet the psychological and social needs of many people with CF. At a
minimum, CF centers recommend avoiding prolonged
close contact between people with CF, and scrupulous
hygiene, including frequent hand washing. Some CF
clinics schedule appointments on different days for
those with and without B. cepacia colonies.
Some doctors choose to prescribe antibiotics only
during infection, while others prefer long-term antibiotic treatment against S. aureus. The choice of antibiotic depends on the particular organism or
organisms found. Some antibiotics are given as aerosols directly into the lungs. Antibiotic treatment may
be prolonged and aggressive.
Supplemental oxygen may be needed as lung disease progresses. Respiratory failure may develop,
requiring temporary use of a ventilator to perform
the work of breathing.
Lung transplantation has become increasingly
common for people with CF, although the number of
people who receive them is still much lower than those
who want them. Transplantation is not a cure, however, and has been likened to trading one disease for
another. Long-term immunosuppression is required,
increasing the likelihood of other types of infection.
About 50% of adults and more than 80% of children
who receive lung transplants live longer than two
years. Liver transplants are also done for CF patients
whose livers have been damaged by fibrosis.
Long-term use of ibuprofen has been shown to
help some people with CF, presumably by reducing
1092

KEY TERMS
Carrier—A person with one copy of a defective
gene, who does not have the disease it causes, but
can pass along the defective gene to offspring.
CFTR—Cystic fibrosis transmembrane conductance regulator, the protein responsible for regulating chloride movement across cells in some tissues.
When a person has two defective copies of the
CFTR gene, cystic fibrosis is the result.
Emphysema—A pathological accumulation of air
in organs or tissues; term especially applied to the
condition when in the lungs.
Mucociliary escalator—The coordinated action of
tiny projections on the surfaces of cells lining the
respiratory tract, which moves mucus up and out of
the lungs.
Mucolytic—An agent that dissolves or destroys
mucin, the chief component of mucus.
Pancreatic insufficiency—Reduction or absence of
pancreatic secretions into the digestive system due
to scarring and blockage of the pancreatic duct.

inflammation in the lungs. Close medical supervision
is necessary, however, since the effective dose is high
and not everyone benefits. Ibuprofen at the required
doses interferes with kidney function, and together
with aminoglycoside antibiotics, may cause kidney
failure.
A number of experimental treatments are currently the subject of much research. Some evidence
indicates that aminoglycoside antibiotics may help
overcome the genetic defect in some CF mutations,
allowing the protein to be made normally. While promising, these results would apply to only about 5% of
those with CF.
Gene therapy is currently the most ambitious
approach to curing CF. In this set of techniques,
non-defective copies of the CFTR gene are delivered
to affected cells, where they are taken up and used to
create the CFTR protein. While elegant and simple in
theory, gene therapy has met with a large number of
difficulties in trials so far, including immune resistance, very short duration of the introduced gene,
and inadequately widespread delivery.

Alternative treatment
In homeopathic medicine, the symptoms of the
disease would be addressed to enhance the quality of
GALE ENCYCLOPEDIA OF MEDICINE



mucolytics to help thin mucus



supplementation of pancreatic enzymes to assist in
digestion



respiratory symptoms can be addressed to open lung
passages



hydrotherapy techniques to help ease the respiratory
symptoms and help the body eliminate



immune enhancements can help revent the development of secondary infections



dietary enhancements and adjustments are used to
treat digestive and nutritional problems

Prognosis
People with CF may lead relatively normal lives,
with the control of symptoms. The possible effect of
pregnancy on the health of a woman with CF requires
careful consideration before beginning a family; as do
issues of longevity, and their children’s status as carriers. Although most men with CF are functionally
sterile, new procedures for removing sperm from the
testes are being tried, and may offer more men the
chance to become fathers.
Approximately half of people with CF live past
the age of 30. Because of better and earlier treatment, a
person born today with CF is expected, on average, to
live to age 40.

Prevention
Adults with a family history of cystic fibrosis may
obtain a genetic test of their carrier status for purposes
of family planning. Prenatal testing is also available.
There is currently no known way to prevent development of CF in a person with two defective gene copies.
Resources
ORGANIZATIONS

Cystic Fibrosis Foundation. 6931 Arlington Road,
Bethesda, MD 20814. (800) 344-4823. <http://
www.cff.org>.
OTHER

CysticFibrosis.com. <http://www.cysticfibrosis.com>.

Richard Robinson
GALE ENCYCLOPEDIA OF MEDICINE

Cystinuria

life for the person with cystic fibrosis. Treating the
cause of CF, because of the genetic basis for the
disease, is not possible. Naturopathic medicine seeks
to treat the whole person, however, and in this
approach might include:

I Cystinuria
Definition
Cystinuria is an inborn error of amino acid transport that results in the defective absorption by the
kidneys of the amino acid called cystine. The name
means ‘‘cystine in the urine.’’

Description
Cystine is an amino acid. Amino acids are organic
compounds needed by the body to make proteins and
for many normal functions. When the kidneys do not
absorb cystine, this compound builds up in the urine.
When the amount of cystine in the urine exceeds its
solubility (the greatest amount that can be dissolved),
crystals form. As the amount of cystine continues to
increase in the urine, the number of crystals also
increases. When very large numbers of cystine crystals
form, they clump together into what is called a stone.

Causes and symptoms
Cystinuria is a rare disease that occurs when people inherit an abnormal gene from their parents. This
disease occurs in differing degrees of severity in people
who have inherited either one or two abnormal genes.
Humans have two copies of each gene. When both are
abnormal, the condition is called homozygous for the
disease. When one copy is normal and the other is
abnormal, the condition is called heterozygous for
the disease. Persons with one abnormal gene can
have a milder form of cystinuria that rarely results in
the formation of stones.
Severe cystinuria occurs when people are homozygous for the disease. For these individuals, the kidneys may excrete as much as 30 times the normal
amount of cystine. Research has shown that this condition is caused by mutations on chromosome number
two (humans have 23 pairs of chromosomes).
A person who has inherited cystinuria may have
other abnormal bodily functions. In addition to excess
levels of the amino acid cystine, high amounts of the
amino acids lysine, arginine, and ornithine are found
in the urine. This condition indicates that these amino
acids are not being reabsorbed by the body.
When excess cystine crystals clump together to
form a stone, the stone can block portions of the interior of the kidney or the tube (the ureter) that connects
the kidney to the urinary bladder. These cystine stones
can be painful, and depending upon where the stone
becomes trapped, the pain can be felt in the lower back
1093

Cystinuria

or the abdomen. Nausea and vomiting can also occur,
and patients may sometimes feel the need to urinate
often. Cystine stones can also cause blood in the urine.
When the urinary tract is blocked by a stone, urinary
tract infections or kidney failure may result.

Diagnosis
Small stones (called ‘‘silent’’) often do not cause
any symptoms, although they can be detected by an x
ray. Large stones are often painful and easily noticed
by the patient. Blood in the urine can also mean that a
stone has formed.
When the urine contains extremely high amounts of
cystine, yellow-brown hexagonal crystals are visible
when a sample is examined under the microscope.
Urine samples can also be mixed with chemicals that
change color when high levels of cystine are present.
When the compound nitroprusside is added to urine
that has been made alkaline by the addition of ammonia,
the urine specimen turns red if it contains excess cystine.

KEY TERMS
Alkaline—A solution is considered alkaline if it
contains fewer hydrogen atoms than pure water.
Amino acid—An organic compound made of an
amino group (containing nitrogen and hydrogen)
and a carbolic acid group. Amino acids are an
essential part of protein molecules.
Nephroscope—An instrument made of a light
source in a tube. The tube is inserted into the kidney
through an incision in the back and used to locate
kidney stones. The stones are broken up with high
frequency sound waves and removed by suction
through the scope.
Nitroprusside—A compound that is used in laboratory tests to identify large amounts of cystine in
urine samples.
Uretoscope—A tube-shaped device inserted into
the body through the urinary system that allows
objects to be both seen and grasped for removal.

Treatment
No treatment can decrease cystine excretion. The
best treatment for cystinuria is to prevent stones from
forming. Stones can be prevented by drinking enough
liquid each day (about 5–7 qts) to produce at least 8 pts
of urine, thus keeping the concentration of cystine
in the urine low. Because a person does not drink
throughout the night, less urine is produced, and the
likelihood of stone formation increases. This risk can
be minimized by drinking water or other liquids just
before going to bed.
Drug treatments
In addition to drinking large amounts of fluids, it is
helpful to make the urine more alkaline. Cystine dissolves more easily in alkaline urine. To increase urine
alkalinity, a person may take sodium bicarbonate and
acetazolamide. Penicillamine, a drug that increases the
solubility of cystine, may be prescribed for patients who
do not respond well to other therapies. This drug must
be used with caution, however, because it can cause
serious side effects or allergic reactions. For those
unable to take penicillamine, another drug, alphamercaptopropionylglycine (Thiola), may be prescribed.
Surgical treatments
Most stones can be removed from the body by
normal urination, helped by drinking large amounts of
water. Large stones that cannot be passed this way
must be removed by surgical procedures.
1094

Large stones can be surgically removed by having
a device called a uretoscope placed into the urethra, up
through the bladder and into the ureter, where the
trapped stone can be seen and removed. Another
method involves using sound-wave energy aimed
from outside the body to break the large stone into
small pieces that can be passed by urination. This
external technique is called extracorporeal shockwave lithotripsy (ESWL).
For large stones in the kidney, a procedure called
percutaneous nephrolithomy may be used. In this
procedure, the surgeon makes a small incision in the
back over the kidney. An instrument called a nephroscope is inserted through the incision into the kidney.
The surgeon uses the nephroscope to locate and
remove the stone. If the stone is very large, it may be
broken up into smaller pieces by an ultrasonic or other
kind of probe before removal.

Prognosis
As many as 50% of patients who have had surgical treatment for a kidney stone will have another
stone within five years if no medicines are used to
treat this condition.

Prevention
Cystinuria is a genetic disorder that currently
cannot be prevented.
GALE ENCYCLOPEDIA OF MEDICINE

Cystitis in children

ORGANIZATIONS

Cystinuria Support Network. 21001 NE 36th St., Redmond,
WA 98053. (425) 868-2996. <http://
www.cystinuria.com>.
National Kidney Foundation. 30 East 33rd St.,
New York, NY 10016. (800) 622-9010. <http://
www.kidney.org>.

In children, cystitis often is caused by congenital
abnormalities (present at birth) of the urinary tract.
Vesicoureteral reflux is a condition in which the child
cannot completely empty the bladder. It allows urine
to remain in or flow backward (reflux) into the partially empty bladder.

Causes and symptoms

Dominic De Bellis, PhD

The causes of cystitis vary according to sex
because of the differences in anatomical structure of
the urinary tract.

I Cystitis
Definition
Cystitis is defined as inflammation of the urinary
bladder. Urethritis is an inflammation of the urethra,
which is the passageway that connects the bladder
with the exterior of the body. Sometimes cystitis and
urethritis are referred to collectively as a lower urinary
tract infection, or UTI. Infection of the upper urinary
tract involves the spread of bacteria to the kidney and
is called pyelonephritis.

Females
Most bladder infections in women are so-called
ascending infections, which means they are caused
by disease agents traveling upward through the urethra to the bladder. The relative shortness of the
female urethra (1.2–2 inches in length) makes it easy
for bacteria to gain entry to the bladder and multiply.
The most common bacteria associated with UTIs in
women include Escherichia coli (about 80% of cases),
Staphylococcus saprophyticus, Klebsiella, Enterobacter,
and Proteus species. Risk factors for UTIs in women
include:


Sexual intercourse. The risk of infection increases if
the woman has multiple partners.



Use of a diaphragm for contraception



An abnormally short urethra



Diabetes or chronic dehydration



The absence of a specific enzyme (fucosyltransferase)
in vaginal secretions. The lack of this enzyme makes
it easier for the vagina to harbor bacteria that cause
UTIs.



Inadequate personal hygiene. Bacteria from fecal
matter or vaginal discharges can enter the female
urethra because its opening is very close to the vagina
and anus.



History of previous UTIs. About 80% of women
with cystitis develop recurrences within two years.

Description
The frequency of bladder infections in humans
varies significantly according to age and sex. The
male/female ratio of UTIs in children younger than
12 months is 4:1 because of the high rate of birth
defects in the urinary tract of male infants. In adult
life, the male/female ratio of UTIs is 1:50. After age 50,
however, the incidence among males increases due to
prostate disorders.
Cystitis in women
Cystitis is a common female problem. It is estimated that 50% of adult women experience at least
one episode of dysuria (painful urination); half of
these patients have a bacterial UTI. Between 2–5%
of women’s visits to primary care doctors are for UTI
symptoms. About 90% of UTIs in women are uncomplicated but recurrent.
Cystitis in men
UTIs are uncommon in younger and middle-aged
men, but may occur as complications of bacterial
infections of the kidney or prostate gland.
GALE ENCYCLOPEDIA OF MEDICINE

The early symptoms of cystitis in women are
dysuria, or pain on urination; urgency, or a sudden
strong desire to urinate; and increased frequency of
urination. About 50% of female patients experience
fever, pain in the lower back or flanks, nausea and
vomiting, or shaking chills. These symptoms indicate
pyelonephritis, or spread of the infection to the upper
urinary tract.
1095

Cystitis

Resources

Cystitis

Males
Most UTIs in adult males are complications of
kidney or prostate infections. They usually are associated with a tumor or kidney stones that block the
flow of urine and often are persistent infections caused
by drug-resistant organisms. UTIs in men are most
likely to be caused by E. coli or another gram-negative
bacterium. S. saprophyticus, which is the second most
common cause of UTIs in women, rarely causes infections in men. Risk factors for UTIs in men include:


Lack of circumcision. The foreskin can harbor bacteria that cause UTIs.



Urinary catheterization. The longer the period of
catheterization, the higher the risk of UTIs.

The symptoms of cystitis and pyelonephritis in
men are the same as in women.
Hemorrhagic cystitis
Hemorrhagic cystitis, which is marked by large
quantities of blood in the urine, is caused by an acute
bacterial infection of the bladder. In some cases,
hemorrhagic cystitis is a side effect of radiation therapy
or treatment with cyclophosphamide. Hemorrhagic
cystitis in children is associated with adenovirus
type 11.

Diagnosis
When cystitis is suspected, the doctor will first
examine the patient’s abdomen and lower back, to
evaluate unusual enlargements of the kidneys or
swelling of the bladder. In small children, the doctor
will check for fever, abdominal masses, and a swollen
bladder.
The next step in diagnosis is collection of a urine
sample. The procedure differs somewhat for women
and men. Laboratory testing of urine samples now can
be performed with dipsticks that indicate immune
system responses to infection, as well as with microscopic analysis of samples. Normal human urine is
sterile. The presence of bacteria or pus in the urine
usually indicates infection. The presence of hematuria,
or blood in the urine, may indicate acute UTIs, kidney
disease, kidney stones, inflammation of the prostate
(in men), endometriosis (in women), or cancer of the
urinary tract. In some cases, blood in the urine results
from athletic training, particularly in runners.
Females
Female patients often require a pelvic examination as part of the diagnostic workup for bladder
1096

infections. Normally, however, a midstream urine
sample of 200 ml is collected to test for infection.
A count of more than 104 bacteria CFU/ml (colony forming units per milliliter) in the midstream
sample indicates a bladder or kidney infection. A
colony is a large number of microorganisms that
grow from a single cell within a substance called a
culture. A bacterial count can be given in CFU or
(colony forming units).
In recent years, many health providers and insurance companies have adopted telephone treatment of
women with presumed cystitis. Trained nurses
diagnose uncomplicated bladder infections over the
telephone based on the patient’s symptoms and a series of questions prepared by physicians. The practice
has been found safe and cost-effective.
Males
In male patients, the doctor will cleanse the opening to the urethra with an antiseptic before collecting
the urine sample. The first 10 ml of specimen are
collected separately. The patient then voids a midstream sample of 200 ml. Following the second sample, the doctor will massage the patient’s prostate and
collect several drops of prostatic fluid. The patient
then voids a third urine specimen for prostatic culture.
A high bacterial count in the first urine specimen
or the prostatic specimens indicates urethritis or prostate infections respectively. A bacterial count greater
than 100,000 bacteria CFU/ml in the midstream sample suggests a bladder or kidney infection.
Other tests
Women with recurrent UTIs can be given ultrasound exams of the kidneys and bladder together with
a voiding cystourethrogram to test for structural
abnormalities. (A cystourethrogram is an x-ray test
in which an iodine dye is used to better view the
urinary bladder and urethra.) Voiding cystourethrograms are also used to evaluate children with UTIs. In
some cases, computed tomography scans (CT scans)
can be used to evaluate patients for possible cancers
in the urinary tract.

Treatment
Medications
Uncomplicated cystitis is treated with antibiotics.
These include penicillin, ampicillin, and amoxicillin;
sulfisoxazole or sulfamethoxazole; trimethoprim;
nitrofurantoin; cephalosporins; or fluoroquinolones.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Bacteriuria—The presence of bacteria in the urine.
Dysuria—Painful or difficult urination.
Hematuria—The presence of blood in the urine.
Pyelonephritis—Bacterial inflammation of the
upper urinary tract.

Patients of either sex may be given phenazopyridine or flavoxate to relieve painful urination.

Urethritis—Inflammation of the urethra, which is
the passage through which the urine moves from
the bladder to the outside of the body.

Trimethoprim and nitrofurantoin are preferred
for treating recurrent UTIs in women.
Over 50% of older men with UTIs also suffer
from infection of the prostate gland. Some antibiotics,
including amoxicillin and the cephalosporins, do not
affect the prostate gland. Fluoroquinolone antibiotics
or trimethoprim are the drugs of choice for these
patients.
Patients with pyelonephritis can be treated with
oral antibiotics or intramuscular doses of cephalosporins. Medications are given for 10–14 days, and
sometimes longer. If the patient requires hospitalization because of high fever and dehydration caused by
vomiting, antibiotics can be given intravenously.
Surgery
A minority of women with complicated UTIs may
require surgical treatment to prevent recurrent infections. Surgery also is used to treat reflux problems
(movement of the urine backward) or other structural
abnormalities in children and anatomical abnormalities in adult males.

Alternative treatment
Alternative treatment for cystitis may emphasize
eliminating all sugar from the diet and drinking lots of
water. Drinking unsweetened cranberry juice not only
adds fluid, but also is thought to help prevent cystitis
by making it more difficult for bacteria to cling to the
bladder wall. A variety of herbal therapies also are
recommended. Generally, the recommended herbs
are antimicrobials, such as garlic (Allium sativum),
goldenseal (Hydrastis canadensis), and bearberry
(Arctostaphylos uva-ursi), and/or demulcents that
soothe and coat the urinary tract, including corn silk
and marsh mallow (Althaea officinalis).
Homeopathic medicine also can be effective in
treating cystitis. Choosing the correct remedy based
on the individual’s symptoms is always key to the
success of this type of treatment. Acupuncture and
GALE ENCYCLOPEDIA OF MEDICINE

Cystitis

(Flouroquinolones generally are not used in children
under 18 years of age.) A 2003 study showed that
fluoroquinolone was preferred over amoxicillin, however, for uncomplicated cystitis in young women.
Treatment for women is short-term; most patients
respond within three days. Men do not respond as
well to short-term treatment and require seven to
10 days of oral antibiotics for uncomplicated UTIs.

Chinese traditional herbal medicine can also be helpful in treating acute and chronic cases of cystitis.

Prognosis
Females
The prognosis for recovery from uncomplicated
cystitis is excellent.
Males
The prognosis for recovery from uncomplicated
UTIs is excellent; however, complicated UTIs in males
are difficult to treat because they often involve bacteria that are resistant to commonly used antibiotics.

Prevention
Females
Women with two or more UTIs within a sixmonth period sometimes are given prophylactic treatment, usually nitrofurantoin or trimethoprim for three
to six months. In some cases the patient is advised to
take an antibiotic tablet following sexual intercourse.
Other preventive measures for women include:


drinking large amounts of fluid



voiding frequently, particularly after intercourse



proper cleansing of the area around the urethra

In 2003, clinical trials in humans were testing a
possible vaccine for recurrent urinary tract infections.
The vaccine was administered via a vaginal
suppository.
Males
The primary preventive measure for males is
prompt treatment of prostate infections. Chronic
prostatitis may go unnoticed, but can trigger recurrent
1097

Cystometry

UTIs. In addition, males who require temporary
catheterization following surgery can be given antibiotics to lower the risk of UTIs.
Resources
PERIODICALS

Harrar, Sari. ‘‘Bladder Infection Protection.’’ Prevention
November 2003: 174.
Jancin, Bruce. ‘‘Presumed Cystitis Well Managed Via
Telephone: Large Kaiser Experience.’’ Family Practice
News November 1, 2003: 41.
Prescott, Lawrence M. ‘‘Presumed Quinolone Gets the Nod
for Uncomplicated Cystitis.’’ Urology Times November
2003: 11.

Rebecca J. Frey, PhD
Teresa G. Odle

I Cystometry
Definition
Cystometry is a test of bladder function in which
pressure and volume of fluid in the bladder is measured during filling, storage, and voiding.

Purpose
The urinary bladder stores urine produced by the
kidneys. The main muscle of the bladder wall, the
detrusor, relaxes to allow expansion of the bladder
during filling. The urethra, the tube through which
urine exits, is held closed by a ring of muscle, known
as the urethral sphincter. As volume increases, stretching of the detrusor and pressure on the sphincter sends
signals to the brain, indicating the need for urination,
or voiding. Voluntary relaxation of the sphincter and
automatic contractions of the detrusor allow successful and virtually complete voiding.
A cystometry study is performed to diagnose
problems with urination, including incontinence,
urinary retention, and recurrent urinary tract infections. Urinary difficulties may occur because of
weak or hyperactive sphincter or detrusor, or incoordination of their two activities. Infection of the bladder or urethra may cause incontinence, as can
obstruction of the urethra from scar tissue, prostate
enlargement, or other benign or cancerous growths.
Loss of sensation due to nerve damage can lead to
chronic overfilling.
1098

Precautions
The mild irritation of the urinary tract necessary
for insertion of the catheter may occasionally cause
flushing, sweating, and nausea.

Description
The patient begins by emptying the bladder as
much as possible. A thin plastic catheter is then slowly
inserted into the urethra until it reaches the bladder.
Measurements are taken of the residual urine volume
and bladder pressure. Pressure measurements may
require a rectal probe to account for the contribution
of the abdominal muscles to the pressure recording.
The bladder is then gradually filled with either
warm water, room temperature water, saline solution,
carbon dioxide gas, or a contrast solution for x-ray
analysis, depending on the type of study being done.
The patient is asked to describe sensations during
filling, including temperature sensations and when
the first feeling of bladder fullness occurs. Once the
bladder is completely full, the patient is asked to begin
voiding, and measurements are again made of pressure
and volume, as well as flow rate and pressure.

Preparation
There is no special preparation needed for this
test. The patient may be asked to stop taking certain
medications in advance of the test, including sedatives,
cholinergics, and anticholinergics.

Aftercare
Cystometry can be somewhat uncomfortable. The
patient may wish to reserve an hour or so afterward
to recover. Urinary frequency or urgency, and some
reddening of the urine, may last for a day. Increasing
fluid intake helps to flush out the bladder, but caffeinated, carbonated, or alcoholic beverages are discouraged, because they may irritate the bladder lining.
Signs of infection, such as fever, chills, low back
pain, or persistent blood in the urine, should be
reported to the examining physician.

Risks
There is a slight risk of infection due to tearing of
the urethral lining.

Normal results
The normal bladder should not begin contractions during filling and should initially expand without
GALE ENCYCLOPEDIA OF MEDICINE

Detrusor—Muscle of the bladder wall.
Sphincter—Ring of muscle between the bladder
and the urethra that functions to close off the urethra.
Urethra—Tube that empties urine from the bladder
to the exterior of the body.

resistance. A feeling of fullness occurs with a volume of
100–200 ml. The adult bladder capacity is 300–500 ml.
The sphincter should relax and open when the patient
wills it, accompanied by detrusor contractions. During
voiding, detrusor contraction should be smooth and
lead to a steady urine stream.

Abnormal results
Inability of the bladder to relax during filling, or
low bladder volume, may indicate interstitial cystitis,
prostate enlargement, or bladder cancer. Contraction
of the bladder during filling may be due to irritation
from infection or cysts, obstruction of the bladder
outlet, or neurological disease such as stroke, multiple
sclerosis, or spinal cord injury. Diminished sensation
may occur with nerve lesions, peripheral neuropathy,
or chronic overfilling.

Purpose
Categorized as an endoscopic procedure, cystoscopy is used by urologists to examine the entire bladder lining and take biopsies of any areas that look
questionable. This test is not used on a routine basis,
but may benefit the urologist who is needing further
information about a patient who displays the following symptoms or diagnosis:


blood in the urine (also known as hematuria)



incontinence or the inabililty to control urination



a urinary tract infection



a urinary tract which display signs of congenital
abnormalities



tumors located in the bladder



the presence of bladder or kidney stones



a stiffness or strained feeling of the urethra or
ureters



symptoms of an enlarged prostate

Blood and urine studies, in addition to x rays of
the kidneys, ureters and bladder may all occur before a
cystoscopy. At the time of surgery, a retrograde pyelogram may also be performed. Additional blood studies
may be needed immediately following surgery.

Resources

Precautions

OTHER

‘‘Cystometrogram, Simple and Complex.’’ HealthGatePage.
<http://www.healthgate.com/HealthGate/free/dph/
static/dph.0085.shtml>.

Richard Robinson

I Cystoscopy
Definition
Cystoscopy (cystourethroscopy) is a diagnostic
procedure that is used to look at the bladder (lower
urinary tract), collect urine samples, and examine the
prostate gland. Performed with an optic instrument
known as a cystoscope (urethroscope), this instrument
uses a lighted tip for guidance to aid in diagnosing
urinary tract disease and prostate disease. Performed
by a urologist, this surgical test also enables biopsies to
GALE ENCYCLOPEDIA OF MEDICINE

While the cystoscopy procedure is commonly
relied upon to gather additional diagnostic information, it is an invasive surgical technique that may
involve risks for certain patients. Those who are extremely overweight (obese), smoke, are recovering from a
recent illness, or are treating a chronic condition may
face additional risks from surgery.
Surgical risk also increases in patients who are
currently using certain drugs including antihypertensives; muscle relaxants; tranquilizers; sleep inducers;
insulin; sedatives; beta blockers; or cortisone. Those
who use mind-altering drugs also put themselves at
increased risk of complications during surgery. The
following mind-altering drugs should be avoided:
narcotics; psychedelics; hallucinogens; marijuana;
sedatives; hypnotics; or cocaine.

Description
Depending on the type of information needed
from a cystoscopy, the procedure typically takes
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Cystoscopy

be taken or small stones to be removed by way of a
hollow channel in the cystoscope.

KEY TERMS

Cystoscopy

Cystoscope

Urethra

Bladder

Prostate gland

Cystoscopy is a diagnostic procedure which is used to view the bladder, collect urine samples, and examine the prostate
gland. This procedure also enables biopsies to be taken. The primary instrument used in cystoscopy is the cystoscope,
a tube which is inserted through the penis into the urethra, and ultimately into the bladder. (Illustration by Electronic
Illustrators Group.)

10–40 minutes to complete. The patient will be asked
to urinate before surgery which allows an accurate
measurement of the remaining urine in the bladder. A
well-lubricated cystoscope is inserted through the
urethra into the bladder where a urine sample is
taken. Fluid is then pushed in to inflate the bladder
and allow the urologist to examine the entire bladder
wall.
During an examination, the urologist may take
the following steps: remove either bladder or kidney
stones; gather tissue samples; and treat any suspicious
lesions. In order to perform x-ray studies (retrograde
pyelogram), a harmless dye is injected into the ureters
by way of a catheter that is passed through the previously placed cystoscope. After completion of all
needed tests, the cystoscope is removed.
1100

Preparation
As procedure that can be completed in a hospital,
doctor’s office, or outpatient surgical facility, an injection of spinal or general anesthesia may be used prior
to a cystoscopy. While this test is typically performed
on an outpatient basis, a patient may require up to
three days of recovery in the hospital.

Aftercare
Patients who have undergone a cystoscopy will be
instructed to follow these steps to ensure a quick
recovery:


due to soreness or discomfort that may occur in the
urethra, especially while urinating, several warm
baths a day are recommended to relieve any pain
GALE ENCYCLOPEDIA OF MEDICINE

Cystoscopy

Cystoscope

Urethra
Bladder

Prostate

A cystoscope helps the doctor examine the urethra, bladder, and prostate. (Illustration by Argosy Inc.)


allow four days for recovery



blood may appear in the urine–this is common, and
soon clears up in one to two days following the
procedure



avoid strenuous exercise for a minimum of two
weeks following surgery



sexual relations may continue when the urologist
determines that healing is complete



wait at least two days after surgery before driving

Patients may also be prescribed pain relievers and
antibiotics following surgery. Minor pain may also be
treated with over-the-counter, non-prescription drugs
such as acetaminophen.

Risks
As with any surgical procedure, there are some risks
involved with a cystoscopy. Complications may include:
profuse bleeding; a damaged urethra; a perforated bladder; a urinary tract infection; or an injured penis.
Patients should also contact their physician if they
experience any of the following symptoms following
surgery: pain, redness, swelling, drainage, or bleeding
from the surgical site; signs of infection that may
include headache, muscle aches, dizziness or an overall
ill feeling and fever; nausea or vomiting; strenuous or
painful urination; or symptoms that may result as
side-effects from the medication.

Normal results
A successful cystoscopy includes a thorough
examination of the bladder and collection of urine
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Endoscopy—Examination of body organs or cavities through the use of an endoscope (a lighted
optical instrument used to see inside body cavities),
such as a cystoscope used to complete a
cystoscopy.
Retrograde pyelogram—A pyelography or x-ray
technique where radiopaque dye is injected into
the kidneys from below, by way of the ureters,
allowing further examination of the kidneys.
Ureter—The tube that carries urine from the kidney to the bladder, with each kidney having one
ureter.
Urethra—A passageway from the bladder to the
outside for the discharge of urine. In the female
this canal lies between the vagina and clitoris; in
the male the urethra travels through the penis,
opening at the tip.

samples for cultures. If no abnormalities are seen, the
results are indicated as normal.

Abnormal results
Cystoscopy allows the urologist to detect inflammation of the bladder lining, prostatic enlargement, or
tumors. If these are seen, further evaluation or biopsies may be needed in addition to the removal of some
tumors.
1101

Cytomegalovirus antibody screening test

Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.

Beth A. Kapes

Cystourethroscopy see Cystoscopy
Cytomegalic inclusion disease see
Cytomegalovirus infection

I Cytomegalovirus
antibody
screening test
Definition
Cytomegalovirus (CMV) is a common human
virus. Antibodies to CMV are evidence of a current
or past infection.

Purpose
Consequences of a CMV infection can be devastating in a pregnant woman, a transplant patient, or a
person with human immunodeficiency virus (HIV).
Antibody screening helps control the infection risk
for these groups.
In a healthy, nonpregnant person, CMV infection
is almost never serious. Symptoms, if present, are
mild, often resembling infectious mononucleosis due
to Epstein-Barr virus. Antibody screening distinguishes between these two infections.

Description
When first exposed to CMV, a person’s immune
system is triggered and quickly makes antibodies to
fight the virus. Antibodies are special proteins
designed to attack and destroy foreign material, in
this case, the cytomegalovirus.
The test combines a person’s serum with a substance to which CMV antibodies attach. This antibody-antigen complex is measured and the amount
of original antibody determined. If positive for antibodies, the serum is diluted, or titered, and the test
repeated until the serum is so dilute it no longer gives a
positive result. The last dilution that gives a positive
result is the titer reported.
1102

A test positive for CMV antibodies means the
person has been infected with the virus, either currently or in the past; it does not mean the person has
lifetime immunity. After an infection, this virus, like
all members of the herpes virus group, can stay hidden
inside a person and cause infection if the person’s
immune system later weakens and antibody protection
decreases. In fact, reactivation of such hidden (or
latent) infection is not at all uncommon and usually
occurs without symptoms.
Transplant patients and people with weakened
immune systems, including those with HIV, are vulnerable to infection from several routes, including
from another person, from a donated organ or transfused blood, or from reactivation of a past infection.
Before transplant, both the recipient and donor are
usually tested for antibodies. A recipient who has
never had CMV (negative for antibodies), should not
receive an organ from a donor who has had CMV
(positive for antibodies). CVM infection can be associated with organ rejection, or can cause illness such as
pneumonia, hepatitis, or death. Similarly, blood is
usually screened for CMV antibodies before being
transfused into a person with a weakened immune
system.
CMV infection is the most common congenital
infection (existing at birth). The infection, passed
from mother to baby, can cause permanent mental or
physical damage, or death. The antibody screening test
tells a woman whether or not she has antibody protection against the virus in case she is exposed during
pregnancy. Pregnant women 25 years and older who
are immune to CMV are much less likely to pass the
virus to their babies than younger women who have
never been exposed to CMV.
Tests that measure a specific type of antibody
help tell the difference between a current and a past
infection. Immunoglobulin M (IgM) antibodies
appear at the beginning of an infection and last only
weeks. Immunoglobulin G (IgG) antibodies appear
10–14 days later and can last a lifetime. A person
suspected of having a current infection should be
tested at the beginning of the infection and again
10–14 days later.
The CMV antibody screening test is also called the
transplant reaction screening test. Results are usually
available the following day.
It may be possible to test fetal blood for certain
antibodies to CMV virus by drawing a blood sample
from the umbilical cord. This may be an important test
to add to prenatal care, since newborn babies with
CMV often show no symptoms.
GALE ENCYCLOPEDIA OF MEDICINE

Antibody—A special protein built by the body as a
defense against foreign material entering the body.
Cytomegalovirus (CMV)—A common human virus
causing mild or no symptoms in healthy people, but
permanent damage or death to an infected fetus, a
transplant patient, or a person with HIV.
Titer—A dilution of a substance with an exact
known amount of fluid. For example, one part of
serum diluted with four parts of saline is a titer
of 1:4.

Gerber, Stefan, et al. ‘‘Prenatal Diagnosis of Congenital
Cytomegalovirus Infection by Detection of
Immunoglobulin M Antibodies to the 70–d Heat Shock
Protein in Fetal Serum.’’ American Journal of Obstetrics
and Gynecology October 2002: 955.

Nancy J. Nordenson
Teresa G. Odle

I Cytomegalovirus infection
Definition

Preparation
The adult CMV antibody screening test requires
5 mL of blood. Collection of the sample takes only a
few minutes.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure
to the puncture site until the bleeding stops reduces
bruising. Warm packs to the puncture site relieve
discomfort.

Normal results
A person without previous exposure to CMV will
test negative.

Abnormal results
The presence of antibodies means the person has
been infected with CMV, either now or in the past. An
antibody titer at least four times higher at the end of
the illness than at the beginning, or the presence of
IgM antibodies, indicates a recent or current first time
infection.
People with weak immune systems may not generate antibodies against CMV. A current infection in a
transplant patient or a person with HIV is confirmed
with other tests, such as viral culture.
Resources
PERIODICALS

Fowler, Karen B., Sergio Stagno, and Robert F. Pass.
‘‘Maternal Immunity and Prevention of Congenital
Cytomegalovirus Infection.’’ JAMA, The Journal of the
American Medical Association February 26, 2003: 1008.
GALE ENCYCLOPEDIA OF MEDICINE

Cytomegalovirus (CMV) is a virus related to the
group of herpes viruses. Infection with CMV can
cause no symptoms, or can be the source of serious
illness in people with weak immune systems. CMV
infection is also an important cause of birth defects.

Description
CMV is an extremely common organism worldwide. It is believed that about 85% of the adults in the
United States have been infected by CMV at some
point in their lives. CMV is found in almost all of the
body’s organs. It is also found in body fluids, including semen, saliva, urine, feces, breast milk, blood, and
secretions of the cervix (the narrow, lower section of
the uterus).
CMV is also able to cross the placenta (the organ
that provides oxygen and nutrients to the unborn baby
in the uterus). Because CMV can cross the placental
barrier, initial infection in a pregnant woman can lead
to infection of the developing baby.

Causes and symptoms
CMV is passed between people through contact
with body fluids. CMV also can be passed through
sexual contact. Babies can be born infected with
CMV, either becoming infected in the uterus (congenital infection) or during birth (from infected cervical
secretions).
Like other herpes viruses, CMV remains inactive
(dormant) within the body for life after the initial
infection. Some of the more serious types of CMV
infections occur in people who have been harboring
the dormant virus, only to have it reactivate when their
immune system is stressed. Immune systems may be
weakened because of cancer chemotherapy, medications given after organ transplantation, or diseases
1103

Cytomegalovirus infection

KEY TERMS

Cytomegalovirus infection

KEY TERMS
Cervix—The narrowed, lowest part of the uterus
through which a baby must pass in order to enter
the birth canal.
Congenital—A condition that exists before birth
and at birth.
Placenta—The organ that provides oxygen and
nutrition from the mother to the unborn baby during pregnancy. The placenta is attached to the wall
of the uterus and leads to the unborn baby via the
umbilical cord.
An infected retina of an AIDS patient. Cytomegaloviruses are
herpes viruses that can, among other problems, act as opportunistic infectious agents in suppressed immune systems, a
common problem with AIDS sufferers. (Custom Medical Stock
Photo. Reproduced by permission.)

that significantly lower immune resistance like
acquired immunodeficiency syndrome (AIDS).
In a healthy person, initial CMV infection often
occurs without symptoms and is rarely noticed.
Occasionally, a first-time infection with CMV may
cause a mild illness called mononucleosis. Symptoms
include swollen glands, liver, and spleen; fever;
increased white blood cells; headache; fatigue; and
sore throat. About 8% of all mononucleosis cases are
due to CMV infection. A similar infection, though
slightly more serious, may occur two to four weeks
after receiving a blood transfusion containing CMV.
In people with weakened immune systems, CMV
infection can cause more serious and potentially lifethreatening illnesses. These illnesses include pneumonia, and inflammations of the liver (hepatitis), brain
(encephalitis), esophagus (esophagitis), large intestine
(colitis), and retina of the eye (retinitis).
Babies who contract CMV from their mothers
during birth rarely develop any illness from these
infections. Infants born prematurely who become
CMV infected during birth have a greater chance
of complications, including pneumonia, hepatitis,
decreased blood platelets.
However, an unborn baby is at great risk for
serious problems when the mother becomes infected
with CMV for the first time while pregnant. About
10% of these babies will be born with obvious problems, including prematurity, lung problems, an
enlarged liver and spleen, jaundice, anemia, low birth
weight, small head size, and inflammation of the
retina. About 90% of these babies may appear perfectly normal at birth. Unfortunately, about 20% will
1104

later develop severe hearing impairments and mental
retardation. A 2003 report found that pregnant women
25 years and older who are immune to CMV are much
less likely to pass the virus to their babies than younger
women who have never been exposed to CMV.

Diagnosis
Body fluids or tissues can be tested to reveal CMV
infection. However, this information is not always particularly helpful because CMV stays dormant in the
cells for life. Tests to look for special immune cells
(antibodies) directed specifically against CMV are useful in proving that a person has been infected with
CMV. However, these tests do not give any information regarding when the CMV infection first occurred.

Treatment
Ganciclovir and foscarnet are both antiviral medications that have been used to treat patients with weak
immune systems who develop a serious illness from
CMV (including retinitis). As of 1998, research was
still being done to try to find useful drugs to treat newborn babies suffering from congenital infection with
CMV. Antiviral drugs are not used to treat CMV infection in otherwise healthy patients because the drugs
have significant side effects that outweigh their benefits.
In 2003, researchers in Europe announced a new compound that appeared to be highly effective against
CMV infections. The new drug acted earlier in the
viral replication of the infection and showed promise,
however, clinical trials were continuing.

Prognosis
Prognosis in healthy people with CMV infection is
excellent. About 0.1% of all newborn babies will have
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Prevention
Prevention of CMV infection in the normal,
healthy person involves good handwashing. Blood
products can be screened or treated to insure that
they do not contain CMV. In 2003, a new high-dose
prophylactic (preventive) treatment was being tested
to reduce CMV risk in stem cell transplant recipients.
Resources

Cytomegalovirus Infection.’’ JAMA, The Journal
of the American Medical Association February 26,
2003: 1008.
‘‘High–Dose Acyclovir May Reduce Cytomegalovirus
Infection Risk.’’ Virus Weekly July 15, 2003: 16.
‘‘Novel Compound Highly Effective Against
Cytomegalovirus Infection.’’ AIDS Weekly November
25, 2003: 17.
ORGANIZATIONS

Baylor College of Medicine. 1 Baylor Plaza, Houston, TX
77030. (713) 798-4951. <http://public.bcm.tmc.edu>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914)
428-7100. resourcecenter@modimes.org. <http://
www.modimes.org>.

PERIODICALS

Fowler, Karen B., Sergio Stagno, and Robert F. Pass.
‘‘Maternal Immunity and Prevention of Congenital

GALE ENCYCLOPEDIA OF MEDICINE

Rosalyn Carson-DeWitt, MD
Teresa G. Odle

1105

Cytomegalovirus infection

serious damage from CMV infection occurring while
they were developing in the uterus. About 50% of all
transplant patients will develop severe illnesses due
to reactivation of dormant CMV infection. These
illnesses have a high rate of serious complications
and death.

D

D & C see Dilatation and curettage

I Dacryocystitis
Definition
Dacryocystitis is an inflammation of the tear sac
(lacrimal sac) at the inner corner of the eye.

Description
Tears drain into little openings (puncta) in the
inner corners of the eyelids. From there, the tears
travel through little tube-like structures (canaliculi)
to the lacrimal sac. The nasolacrimal ducts then take
the tears from the lacrimal sac to the nose. That’s why
people need to blow their nose when they cry a lot.
Dacryocystitis is usually caused by a blockage of
the nasolacrimal duct, which allows fluid to drain into
the nasal passages. When the lacrimal sac does not
drain, bacteria can grow in the trapped fluid. This
condition is most common in infants and people over
40 years old.

Causes and symptoms
In newborn infants, the nasolacrimal duct may
fail to form an opening–a condition called dacryostenosis. The cause of dacryocystitis in adults is usually
associated with inflammation and infection in the
nasal region. Dacryocystitis can be acute, having a
sudden onset, or it can be chronic, with symptoms
occurring over the course of weeks or months.
Symptoms of acute dacryocystitis can include pain,
redness, tearing, and swelling at the inner corner of
the eye by the nose. In chronic dacryocystitis, the eye
area may be swollen, watery or teary, and, when
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pressure is applied to the area, there may be a discharge of pus or mucus through the punctum.

Diagnosis
Dacryocystitis usually occurs in only one eye. As
mentioned, the symptoms can range from watery eyes,
pain, swelling, and redness to a discharge of pus when
pressure is applied to the area between the bridge of
the nose and the inner eyelids. A sample of the pus may
be collected on a swab or in a tube for laboratory
analysis. The type of antibiotic and treatment may
depend on which bacteria is present. In the acute
form, a blood test may reveal an elevated white
blood cell (WBC) count; with a chronic infection, the
WBC count is usually normal. To identify the exact
location of the blockage, an x ray can be taken after a
dye is injected into the duct in a procedure called
dacryocystography.

Treatment
A warm compress applied to the area can help
relieve pain and promote drainage. Topical and oral
antibiotics may be prescribed if an infection is present.
Intravenous antibiotics may be needed if the infection
is severe. In some cases, a tiny tube (cannula) is
inserted into the tear duct which is then flushed with
a sterile salt water solution (sterile saline). If other
treatments fail to clear up the symptoms, surgery
(dacryocystorhinostomy) to drain the lacrimal sac
into the nasal cavity can be performed. In extreme
cases, the lacrimal sac will be removed completely.
In infants, gentle massage of the lacrimal sac four
times daily for up to nine months can drain the sac and
sometimes clear a blockage. As the infant grows, the
duct may open by itself. If the duct does not open, it
may need to be dilated with a minor surgical procedure.
1107

Death

present. If there is a permanent blockage that prevents
drainage, infection may recur and surgery may be
required to open the duct. If left untreated, the infected
sac can rupture, forming an open, draining sore.

Prevention
There are no specific recommendations for the
prevention of dacryocystitis, however, good hygiene
may decrease the chances of infection.
Resources
BOOKS

Gorbach, Sherwood L., John G. Bartlett, and Neil R.
Blacklow, editors. ‘‘Dacryocystitis.’’ In Infectious
Diseases. 2nd ed. Philadelphia: W. B. Saunders Co., 1998.

Altha Roberts Edgren

Dacryocystitis of the right eye. The inner corner of the lower
lid is bulging from an inflamed tear sac. Blockage of the tear
duct causes fluid to be trapped in the tear sac, which
becomes infected. (Custom Medical Stock Photo. Reproduced
by permission.)

Dandruff see Seborrheic dermatitis

I Death
KEY TERMS
Canaliculi—Also known as lacrimal ducts, these
tube-like structures carry the tears from the eyes to
the lacrimal sac.
Cannula— A narrow tube that can be inserted into
a duct.
Dacryocystography—An x ray of the tear duct after
injection of a dye that is used to help locate a
blockage in the duct.
Dacryocystorhinostomy—A surgical procedure to
drain the tear sac into the nasal passage.
Dacryostenosis—Obstruction or narrowing of the
nasolacrimal duct. May be present at birth.
Nasoacrimal duct—The tube that carries the tears
from the lacrimal sac to the nose.
Punctum—Tiny opening at the inner corners of the
upper and lower lids. The area for the beginning of
tear drainage.

Prognosis
Treatment of dacryocystitis with antibiotics is
usually successful in clearing the infection that is
1108

Definition
Death is defined as the cessation of all vital functions of the body including the heartbeat, brain activity (including the brain stem), and breathing.

Description
Death comes in many forms, whether it be
expected after a diagnosis of terminal illness or an
unexpected accident or medical condition.
Terminal illness
When a terminal illness is diagnosed, a person,
family, friends, and physicians are all able to prepare
for the impending death. A terminally ill individual goes
through several levels of emotional acceptance while in
the process of dying. First, there is denial and isolation.
This is followed by anger and resentment. Thirdly, a
person tries to escape the inevitable. With the realization
that death is eminent, most people suffer from depression. Lastly, the reality of death is realized and accepted.

Causes and symptoms
The two leading causes of death for both men
and women in the United States are heart disease
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A contemporary physician who was a world authority
on the subject of death and after-death states. Born in
Switzerland on July 8, 1926, she worked as a country
doctor before moving to the United States. During World
War II she spent weekends at the Kantonspital (Cantonai
Hospital) in Zürich, where she volunteered to assist
escaped refugees. After the war she visited Majdanek concentration camp, where the horrors of the death chambers
stimulated in her a desire to help people facing death and to
understand the human impulses of love and destruction.
She extended her medical background by becoming a
practicing psychiatrist. Her formal work with dying patients
began in 1965 when she was a faculty member at the
University of Chicago. She also conducted research on
basic questions concerning life after death at the
Manhattan State Hospital, New York. Her studies of death
and dying involved accounts by patients who reported outof-the-body travel. Her research tends to show that while
dying can be painful, death itself is a peaceful condition.
Her 1969 text, On Death and Dying, was hailed by her
colleagues and also became a popular best-seller.
In 1978 Kübler-Ross helped to found Shanti Nilaya
(Final Home of Peace), a healing and growth center in
Escondido, California. This was an extension of her
well-known "Life-Death and Transition" workshops
conducted in various parts of the United States and
Canada, involving physicians, nurses, social workers,
laypeople, and terminally ill patients. Much of KüblerRoss’s later research was directed toward proving the
existence of life after death. Her publication To Live
Until We Say Good-bye (1979) was both praised as a
"celebration of life" and criticized as "prettifying" the real
situation. She also dealt with issues such as AIDS and
"near death" experiences. In the mid-1980s, Shanti
Nilaya moved from San Diego County, California, to
Head Waters, Virginia, where it continues to offer
courses and short- and long-term therapeutic sessions.

and cancer. Accidental death was a distant third followed by such problems as stroke, chronic lung disorders, pneumonia, suicide, cirrhosis, diabetes mellitus,
and murder. The order of these causes of death varies
among persons of different age, ethnicity, and gender.

Diagnosis
In an age of organ transplantation, identifying the
moment of death may now involve another life. It
thereby takes on supreme legal importance. It is largely due to the need for transplant organs that death
has been so precisely defined.
GALE ENCYCLOPEDIA OF MEDICINE



no pupil reaction to light



no response of the eyes to caloric (warm or cold)
stimulation



no jaw reflex (the jaw will react like the knee if hit
with a reflex hammer)



no gag reflex (touching the back of the throat induces
vomiting)



no response to pain



no breathing



a body temperature above 86 8F (30 8C), which
eliminates the possibility of resuscitation following
cold-water drowning



no other cause for the above, such as a head injury



no drugs present in the body that could cause apparent death



all of the above for 12 hours



all of the above for six hours and a flat-line electroencephalogram (brain wave study)



no blood circulating to the brain, as demonstrated by
angiography

Current ability to resuscitate people who have
‘‘died’’ has produced some remarkable stories.
Drowning in cold water (under 50 8F/10 8C) so effectively slows metabolism that some persons have been
revived after a half hour under water.

Treatment
Only recently has there been concerted public
effort to address the care of the dying in an effort to
improve their comfort and lessen their alienation from
those still living. Hospice care represents one of the
greatest advances made in this direction. There has
also been a liberalization of the use of narcotics and
other drugs for symptomatic relief and improvement
in the quality of life for the dying.
Living will
One of the most difficult issues surrounding death in
the era of technology is that there is now a choice, not of
the event itself, but of its timing. When to die, and more
often, when to let a loved one die, is coming within
people’s power to determine. This is both a blessing and
a dilemma. Insofar as the decision can be made ahead of
time, a living will is an attempt to address this dilemma.
By outlining the conditions under which one would
rather be allowed to die, a person can contribute significantly to that final decision, even if not competent to do
1109

Death

The official signs of death include the following:

E L I S A B E T H K ÜB L E R - R O S S
(1926–2004)

Death

KEY TERMS
Angiography—X rays of blood vessels filled with a
contrast agent.
Caloric testing—Flushing warm and cold water into
the ear stimulates the labyrinth and causes vertigo
and nystagmus if all the nerve pathways are intact.
Electroencephalogram—Recording of electrical
activity in the brain.
Hospice—Systematized care of dying persons.
Living will—A legal document detailing a person’s
wishes during the end of life, to be carried out by
designated decision makers.
Stroke—Interruption of blood flow to a part of the
brain with consequent brain damage, also known
as a cerebrovascular accident (CVA).

so at the time of actual death. The problem is that there
are uncertainties surrounding every severely ill person.
Each instance presents a greater or lesser chance of survival. The chance is often greater than zero. The best
living will follows an intimate discussion with decision
makers covering the many possible scenarios surrounding the end of life. This discussion is difficult, for few
people like to contemplate their own demise. However,
the benefits of a living will are substantial, both to physicians and to loved ones who are faced with making final
decisions. Most states have passed living will laws, honoring instructions on artificial life support that were made
while a person was still mentally competent.
Euthanasia
Another issue that has received much attention is
assisted suicide (euthanasia). In 1997, the State of
Oregon placed the issue on the ballot, amid much
consternation and dispute. Perhaps the main reason
euthanasia has become front page news is because
Dr. Jack Kevorkian, a pathologist from Michigan, is
one of its most vocal advocates. The issue highlights the
many new problems generated by increasing ability to
intervene effectively in the final moments of life and
unnaturally prolong the process of dying. The public
appearance of euthanasia has also stimulated discussion about more compassionate care of the dying.

Prevention
Autopsy after death is a way to precisely determine
a cause of death. The word autopsy is derived from
1110

Greek meaning to see with one’s own eyes. A pathologist extensively examines a body and submits a
detailed report to an attending physician. Although
an autopsy can do nothing for an individual after
death, it can benefit the family and, in some cases,
medical science. Hereditary disorders and disease
may be found. This knowledge could be used to prevent illness in other family members. Information
culled from an autopsy can be used to further medical
research. The link between smoking and lung cancer
was confirmed from data gathered through autopsy.
Early information about AIDS was also compiled
through autopsy reports.
Resources
BOOKS

Finkbeiner, J. Autopsy: A Manual & Atlas. Philadelphia:
Saunders, 2001.
Iserson, Kenneth B. Death to Dust: What Happens to
DeadBodies? Tucson: Galen Press Ltd, 2001.
Mount, Balfour M. ‘‘Care of Dying Patients and Their
Families.’’In Cecil Textbook of Medicine, edited by Lee
Goldman, et al., 21st ed. Philadelphia: W.B. Saunders,
2000.
Sheaff, Michael T., and Deborah J. Hopster. Post Mortem
Technique Handbook. New York: Springer Verlag,
2001.
PERIODICALS

Roger, V. L., et al. ‘‘Time Trends in the Prevalence of
Atherosclerosis: A Population-based Autopsy Study.’’
American Journal of Medicine 110, no. 4 (2001): 267-273.
Targonski, P., et al. ‘‘Referral to Autopsy: Effect of
AtemortemCardiovascular Disease. A Populationbased Study in Olmsted County, Minnesota.’’ Annals of
Epidemiology 11, no. 4 (2001): 264-270.
ORGANIZATIONS

American Academy of Family Physicians. 11400
Tomahawk Creek Parkway, Leawood, KS 66211-2672.
(913) 906-6000. <http://www.aafp.org>.
American Medical Association. 515 N. State Street,
Chicago, IL 60610. (312) 464-5000. <http://www.amaassn.org>.
American Society of Clinical Pathologists. 2100 West
Harrison Street, Chicago, IL 60612. (312) 738-1336.
<http://www.ascp.org/index.asp>.
College of American Pathologists. 325 Waukegan Road,
Northfield, IL 60093. (800) 323-4040. <http://
www.cap.org>.
Hospice Foundation of America. 2001 S St. NW Suite 300,
Washington, DC 20009. (800) 854-3402. <http://
www.hospicefoundation.org>.
OTHER

American Association of Retired Persons. <http://
www.aarp.org>.
GALE ENCYCLOPEDIA OF MEDICINE

L. Fleming Fallon, Jr., MD, DrPH

I Debridement
Definition
Debridement is the process of removing nonliving tissue from pressure ulcers, burns, and other
wounds.

Purpose
Debridement speeds the healing of pressure
ulcers, burns, and other wounds. Wounds that contain
non-living (necrotic) tissue take longer to heal. The
necrotic tissue may become colonized with bacteria,
producing an unpleasant odor. Though the wound is
not necessarily infected, the bacteria can cause inflammation and strain the body’s ability to fight infection.
Necrotic tissue may also hide pockets of pus called
abscesses. Abscesses can develop into a general infection that may lead to amputation or death.

Precautions
Not all wounds need debridement. Sometimes it is
better to leave a hardened crust of dead tissue, called
an eschar, than to remove it and create an open
wound, particularly if the crust is stable and the
wound is not inflamed. Before performing debridement, the physician will take a medical history with
attention to factors that might complicate healing,
such as medications being taken and smoking. The
physician will also note the cause of the wound and
the ways it has been treated. Some ulcers and other
wounds occur in places where blood flow is impaired,
for example, the foot ulcers that can accompany diabetes mellitus. In such cases, the physician or nurse
may decide not to debride the wound because blood
flow may be insufficient for proper healing.

Description
In debridement, dead tissue is removed so that the
remaining living tissue can adequately heal. Dead
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tissue exposed to the air will form a hard black crust,
called an eschar. Deeper tissue will remain moist and
may appear white, or yellow and soft, or flimsy. The
four major debridement techniques are surgical,
mechanical, chemical, and autolytic.
Surgical debridement
Surgical debridement (also known as sharp debridement) uses a scalpel, scissors, or other instrument to
cut dead tissue from a wound. It is the quickest and
most efficient method of debridement. It is the preferred method if there is rapidly developing inflammation of the body’s connective tissues (cellulitis) or a
more generalized infection (sepsis) that has entered the
bloodstream. The procedure can be performed at a
patient’s bedside. If the target tissue is deep or close
to another organ, however, or if the patient is experiencing extreme pain, the procedure may be done in an
operating room. Surgical debridement is generally
performed by a physician, but in some areas of the
country an advance practice nurse or physician assistant may perform the procedure.
The physician will begin by flushing the area with a
saline (salt water) solution, and then will apply a topical
anesthetic gel to the edges of the wound to minimize
pain. Using a forceps to grip the dead tissue, the physician will cut it away bit by bit with a scalpel or scissors.
Sometimes it is necessary to leave some dead tissue
behind rather than disturb living tissue. The physician
may repeat the process again at another session.
Mechanical debridement
In mechanical debridement, a saline-moistened
dressing is allowed to dry overnight and adhere to
the dead tissue. When the dressing is removed, the
dead tissue is pulled away too. This process is one of
the oldest methods of debridement. It can be very
painful because the dressing can adhere to living as
well as nonliving tissue. Because mechanical debridement cannot select between good and bad tissue, it is
an unacceptable debridement method for clean
wounds where a new layer of healing cells is already
developing.
Chemical debridement
Chemical debridement makes use of certain
enzymes and other compounds to dissolve necrotic tissue. It is more selective than mechanical debridement.
In fact, the body makes its own enzyme, collagenase, to
break down collagen, one of the major building blocks
of skin. A pharmaceutical version of collagenase is
available and is highly effective as a debridement
1111

Debridement

Association for Death Education and Counseling. <http://
www.adec.org>.
Death and Dying Grief Support. <http://www.deathdying.com>.
National Center for Health Statistics. <http://www.cdc.gov/
nchs>.

Debridement
A burn sufferer undergoes debridement (the removal of dead skin). The patterns on his chest are from skin grafts. (Photograph
by Ann Chawatsky, Phototake NYC. Reproduced by permission.)

agent. As with other debridement techniques, the area
first is flushed with saline. Any crust of dead tissue is
etched in a cross-hatched pattern to allow the enzyme to
penetrate. A topical antibiotic is also applied to prevent
introducing infection into the bloodstream. A moist
dressing is then placed over the wound.
Autolytic debridement
Autolytic debridement takes advantage of the
body’s own ability to dissolve dead tissue. The key to
the technique is keeping the wound moist, which can
be accomplished with a variety of dressings. These
dressings help to trap wound fluid that contains
growth factors, enzymes, and immune cells that promote wound healing. Autolytic debridement is more
selective than any other debridement method, but it
also takes the longest to work. It is inappropriate for
wounds that have become infected.

Preparation
The physician or nurse will begin by assessing the
need for debridement. The wound will be examined,
1112

KEY TERMS
Eschar—A hardened black crust of dead tissue that
may form over a wound.
Pressure ulcer—Also known as a decubitus ulcer,
pressure ulcers are open wounds that form whenever prolonged pressure is applied to skin covering
bony outcrops of the body. Patients who are bedridden are at risk of developing pressure ulcers.
Pressure ulcers are commonly known as bedsores.
Sepsis—A severe systemic infection in which bacteria have entered the blood stream.

frequently by inserting a gloved finger into the wound
to estimate the depth of dead tissue and evaluate
whether it lies close to other organs, bone, or important body features. The area may be flushed with a
saline solution before debridement begins, and a topical anesthetic gel or injection may be applied if surgical
or mechanical debridement is being performed.
GALE ENCYCLOPEDIA OF MEDICINE

After surgical debridement, the wound will be
packed with a dry dressing for a day to control bleeding. Afterward, moist dressings are applied to promote
wound healing. Moist dressings are also used after
mechanical, chemical, and autolytic debridement.
Many factors contribute to wound healing, which frequently can take considerable time. Debridement may
need to be repeated.

Risks
It is possible that underlying tendons, blood vessels or other structures will be damaged during the
examination of the wound and during surgical debridement. Surface bacteria may also be introduced deeper
into the body, causing infection.

Normal results
Removal of dead tissue from pressure ulcers
and other wounds speeds healing. Although these
procedures cause some pain, they are generally well
tolerated by patients and can be managed more
aggressively. It is not uncommon to debride a wound
again in a subsequent session.
Resources
ORGANIZATIONS

American Academy of Wound Management. 1255 23rd St.,
NW, Washington, DC 20037. (202) 521-0368. <http://
www.aawm.org>.
Wound Care Institute. 1100 N.E. 163rd Street, Suite #101,
North Miami Beach, FL 33162. (305) 919-9192.
<http://woundcare.org>.

Richard H. Camer

I Decompression sickness
Definition
Decompression sickness (DCS) is a dangerous
and occasionally lethal condition caused by nitrogen
bubbles that form in the blood and other tissues of
scuba divers who surface too quickly.

Description
According to the Divers Alert Network (DAN), a
worldwide organization devoted to safe-diving research
GALE ENCYCLOPEDIA OF MEDICINE

and promotion, less than 1% of divers fall victim to DCS
or the rarer bubble problem called gas embolism, air
embolism, or arterial gas embolism (AGE). A study of
the United States military community in Okinawa, where
tens of thousands of sport and military dives are made
each year, identified 84 DCS and 10 AGE cases in 1989–
95, including nine deaths. This translated into estimates
of one case in every 7,400 dives and one death in every
76,900 dives. DCS symptoms can be quite mild, however,
and many cases certainly go unnoticed by divers.
At times the terminology adopted by writers on DCS
can be confusing. Some substitute the term decompression illness (DCI) for DCS. Others treat DCI as a label
encompassing both DCS and AGE. An older term for
DCS is caisson disease, coined in the nineteenth century
when it was discovered that bridge construction crews
working at the bottom of lakes and rivers in large pressurized enclosures (caissons) were experiencing joint pain
(a typical DCS symptom) on returning to the surface.

Causes and symptoms
The air we breathe is mostly a mixture of two gases,
nitrogen (78%) and oxygen (21%). Unlike oxygen,
nitrogen is a biologically inert gas, meaning that it is
not metabolized (converted into other substances) by
the body. For this reason, most of the nitrogen we
inhale is expelled when we exhale, but some is dissolved
into the blood and other tissues. During a dive, however, the lungs take in more nitrogen than usual. This
happens because the surrounding water pressure is
greater than the air pressure at sea level (twice as great
at 33 ft [10 m], for instance). As the water pressure
increases, so does the pressure of the nitrogen in the
compressed air inhaled by the diver. Because increased
pressure causes an increase in gas density, the diver
takes in more nitrogen with each breath than he or she
would at sea level. Instead of being exhaled, however,
the extra nitrogen safely dissolves into the tissues, where
it remains until the diver begins his or her return to the
surface (under some circumstances the extra nitrogen
can cause nitrogen narcosis, but that condition is distinct from DCS). On the way up, decompression occurs
(in other words, the water pressure drops), and with the
change in pressure, the extra nitrogen gradually diffuses
out of the tissues and is delivered by the bloodstream to
the lungs, which expel it from the body. If the diver
surfaces too quickly, however, potentially dangerous
nitrogen bubbles can form in the tissues and cause
DCS. These bubbles can compress nerves, obstruct
arteries, veins, and lymphatic vessels, and trigger harmful chemical reactions in the blood. The precise reasons
for bubble formation remain unclear.
1113

Decompression sickness

Aftercare

Decompression sickness

How much extra nitrogen enters the tissues varies
with the dive’s depth and duration. Dive tables prepared
by the U.S. Navy and other organizations specify how
long most divers can safely remain at a particular depth.
If the dive table limits are exceeded, the diver must pause
on the way up to allow the nitrogen to diffuse into the
bloodstream without forming bubbles; these pauses are
called decompression stops, and are carefully calibrated.
DCS can occur, however, even when a diver obeys safe
diving rules. In such cases, the predisposing factors
include fatigue, obesity, dehydration, hypothermia, and
recent alcohol use. People who fly or travel to highaltitude locations without letting 12–24 hours pass
after their last dive are at risk for DCS as well because
their bodies undergo further decompression. This is true
even when flying in commercial aircraft. Many travelers
are unaware that to save money on fuel the cabin pressure in commercial aircraft is set much lower than the
pressure at sea level. At 30,000 ft (9,144 m), for instance,
cabin pressure is usually equivalent to the pressure at
7,000–8,000 ft (2,133–2,438 m) above sea level, a safe
setting for everyone but recent divers. Exactly how long
a diver should wait before flying or traveling to a highaltitude location depends on how much diving he or she
has done and other considerations. If there is uncertainty
about the appropriate waiting period, the sensible
course of action is to let the full 24 hours pass.
Because the nitrogen bubbles that cause DCS can
affect any of the body’s tissues, including the blood,
bones, nerves, and muscles, many kinds of symptoms are
possible. Symptoms can appear minutes after a diver surfaces, and in about 80% of cases do so within eight hours.
Pain is often the only symptom; this is sometimes called
the bends, although many people incorrectly use that term
as a synonym for DCS itself. The pain, which ranges from
mild to severe, is usually limited to the joints, but can be felt
anywhere. Severe itching (pruritis), skin rashes, and
skin mottling (cutis marmorata) are other possible symptoms. All of these are sometimes classified as manifestations of type 1 or ‘‘mild’’ DCS. Type 2 or ‘‘serious’’ DCS
can lead, among other things, to paralysis, brain damage,
heart attacks, and death. Many DCS victims, however,
experience both type 1 and type 2 symptoms.

Diagnosis
Diagnosis requires taking a medical history (questioning the patient about his or her health and recent
activities) and conducting a physical examination.

Treatment
DCS is treated by giving the patient oxygen and
placing him or her in a hyperbaric chamber, an
1114

KEY TERMS
Gas embolism—The presence of a gas bubble in
the bloodstream that obstructs circulation.
Hyperbaric chamber—A sealed compartment in
which air pressure is gradually increased and then
gradually decreased, allowing nitrogen bubbles to
shrink and the nitrogen to safely diffuse out of body
tissue.
Lymphatic vessels—Vessels that carry a fluid called
lymph from the tissues to the bloodstream.
Nitrogen narcosis—Also called ‘‘rapture of the
deep,’’ the condition is caused by increased nitrogen pressure at depth and is characterized by symptoms similar to alcohol intoxication.

enclosure in which the air pressure is first gradually
increased and then gradually decreased. This shrinks
the bubbles and allows the nitrogen to safely diffuse
out of the tissues. Hyperbaric chamber facilities exist
throughout the United States. No matter how mild
one’s symptoms may appear, immediate transportation to a facility is essential. Treatment is necessary
even if the symptoms clear up before the facility is
reached, because bubbles may still be in the bloodstream and pose a threat. DAN maintains a list of
facilities and a 24-hour hotline that can provide advice
on handling DCS and other diving emergencies.

Prognosis
DCS sufferers who undergo chamber treatment
within a few hours of symptom onset usually enjoy a
full recovery. If treatment is delayed the consequences
are less predictable, although many people have been
helped even after several days have passed. A 1992
DAN report on diving accidents indicated that full
recovery following chamber treatment was immediate
for about 50% of divers. Some people, however, suffer
numbness, tingling, or other symptoms that last weeks,
months, or even a lifetime. In the Okinawa study, six
of the 94 patients experienced ‘‘long-lasting’’ symptoms even after repeated chamber treatments.

Prevention
The obvious way to minimize the risk of falling
victim to DCS is to follow the rules on safe diving and
air travel after a dive. People who are obese, suffer
from lung or heart problems, or are otherwise in poor
health should not dive. And because the effect of
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

American College of Hyperbaric Medicine. PO Box 25914130, Houston, Texas 77265. (713) 528-0657. <http://
www.hyperbaricmedicine.org>.
Divers Alert Network. The Peter B. Bennett Center, 6 West
Colony Place, Durham, NC 27705. (800) 446-2671.
<http://www.diversalertnetwork.org>.
Undersea and Hyperbaric Medical Society. 10531
Metropolitan Ave., Kensington, MD 20895. (301) 9422980. <http://www.uhms.org>.

Howard Baker

I Decongestants
Definition
Decongestants are medicines used to relieve nasal
congestion (stuffy nose).

Purpose
A congested or stuffy nose is a common symptom
of colds and allergies. This congestion results when
membranes lining the nose become swollen.
Decongestants relieve the swelling by narrowing the
blood vessels that supply the nose. This reduces the
blood supply to the swollen membranes, causing
the membranes to shrink.
These medicines do not cure colds or reverse the
effects of histamines—chemicals released as part of the
allergic reaction. They will not relieve all of the symptoms
associated with colds and allergies, only the stuffiness.
When considering whether to use a decongestant
for cold symptoms, keep in mind that most colds go
away with or without treatment and that taking medicine is not the only way to relieve a stuffy nose.
Drinking hot tea or broth or eating chicken soup
may help. There are also adhesive strips can be placed
on the nose to help widen the nasal passages, making
breathing through the nasal passages a bit easier when
congestion is present.

Precautions
Decongestant nasal sprays and nose drops may
cause a problem called rebound congestion if used
GALE ENCYCLOPEDIA OF MEDICINE

repeatedly over several days. When this happens, the
nose remains stuffy or gets worse with every dose. The
only way to stop the cycle is to stop using the drug.
The stuffiness should then go away within about a
week. Anyone who shows signs of severe rebound
congestion should also contact his or her physician.
Do not use decongestant nasal sprays for more
than three days. Decongestants taken by mouth
should not be used for more than seven days. If the
congestion has not gone away in this time, or if the
symptoms are accompanied by fever, call a physician.
Do not use a decongestant nasal spray after the
product’s expiration date. If the product has become
cloudy or discolored, throw it away and do not use it.
Do not share droppers or spray bottles with anyone
else, as this could spread infection. Do not let droppers
and bottle tips touch countertops or other surfaces.
Some decongestants cause drowsiness. People
who takes these drugs should not drive, use machines
or do anything else that might be dangerous until they
have found out how the drugs affect them.
In general, older people may be more sensitive to
the effects of decongestants and may need to take
lower doses to avoid side effects. People in this age
group should not take long-acting (extended release)
forms of decongestants unless they have previously
taken a short-acting form with no ill effects.
Children may also be more sensitive to the effects
of decongestants. Before giving any decongestant to a
child, check the package label carefully. Some of these
medicines are too strong for use in children. Serious
side effects are possible if they are given large amounts
of these drugs or if they swallow nose drops, nasal
spray or eye drops. If this happens, call a physician
or poison center immediately.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take decongestants. Before taking these drugs, be
sure to let the physician know about any of these
conditions:
ALLERGIES. Anyone who has had unusual reactions to decongestants in the past should let his or
her physician know before these drugs or any similar
drugs are prescribed. The physician should also be told
about any allergies to foods, dyes, preservatives, or
other substances.
PREGNANCY. In studies of laboratory animals,
some decongestants have had unwanted effects on
fetuses. However, it is not known whether such effects

1115

Decongestants

nitrogen diffusion on the fetus remains unknown,
diving while pregnant is not recommended.

Decongestants

also occur in people. Women who are pregnant or who
plan to become pregnant should check with their physicians before taking decongestants.
BREASTFEEDING. Some decongestants pass into

breast milk and may have unwanted effects on nursing
babies whose mothers take the drugs. Women who
are breastfeeding should check with their physicians
before using decongestants. If they need to take the
medicine, it may be necessary to bottle feed the baby
with formula while taking it.

while taking decongestants should stop taking them
immediately.
Patients who have these symptoms while taking
decongestants should call the physician immediately:


increased blood pressure



fast, irregular, or fluttery heartbeat



severe headache



tightness or discomfort in the chest



breathing problems

or blood vessel disease, high blood pressure, diabetes,
enlarged prostate, or overactive thyroid should not
take decongestants unless under a physician’s supervision. The medicine can increase blood sugar in people with diabetes. It can be especially dangerous in
people with high blood pressure, as it may increase
blood pressure.



fear or anxiety



hallucinations



trembling or shaking



convulsions (seizures)



pale skin



painful or difficult urination

Before using decongestants, people with any of
these medical problems should make sure their physicians are aware of their conditions:

Other side effects may occur. Anyone who has
unusual symptoms after taking a decongestant should
get in touch with his or her physician.

OTHER MEDICAL CONDITIONS. Anyone with heart



glaucoma



history of mental illness

Decongestants may have a variety of side effects,
and may also interact with other medications the
patient is taking.

Interactions with other medicines
Decongestants may interact with a variety of
other medicines. When this happens, the effects of
one or both of the drugs may change or the risk
of side effects may be greater. Do not take decongestants at the same time as these drugs:

Side effects


Monoamine oxidase inhibitors (MAO inhibitors)
such as phenzeline (Nardil) or tranylcypromine
(Parnate), used to treat conditions including depression and Parkinson’s disease. Do not take decongestants at the same time as a MAO inhibitor or within
two weeks of stopping treatment with an MAO
inhibitor unless a physician approves.



Other products containing the same or other
decongestants



Caffeine.

DECONGESTANT NASAL SPRAYS AND NOSE
DROPS. The most common side effects from deconges-

tant nasal sprays and nose drops are sneezing and
temporary burning, stinging, or dryness. These effects
are usually temporary and do not need medical attention. If any of the following side effects occur after
using a decongestant nasal spray or nose drops, stop
using the medicine immediately and call the physician:


increased blood pressure



headache



fast, slow, or fluttery heartbeat



nervousness



dizziness



nausea



sleep problems

DECONGESTANTS TAKEN BY MOUTH. The most
common side effects of decongestants taken by
mouth are nervousness, restlessness, excitability, dizziness, drowsiness, headache, nausea, weakness, and
sleep problems. Anyone who has these symptoms

1116

In addition, anyone who takes decongestants
should let the physician know all other medicines he
or she is taking. Among the drugs that may interact
with decongestants are:


tricyclic antidepressants such as imipramine
(Tofranil) or desipramine (Norpramin)



the antidepressant maprotiline (Ludiomil)



amantadine (Symmetrel)



amphetamines



medicine to relieve asthma or other breathing problems



methylphenidate (Ritalin)
GALE ENCYCLOPEDIA OF MEDICINE

Fetus—A developing baby inside the womb.
Hallucination—A false or distorted perception of
objects, sounds, or events that seems real.
Hallucinations usually result from drugs or mental
disorders.

medicine cabinet. In 2000, the Food and Drug
Administration prohibited over-the-counter sales of
medicines containing the decongestant phenylpropanolamine. The medicine is associated with an
increased risk of stroke in people ages 18 to 49, especially women. Many cold remedies contained this
medicine. Contact a pharmacist if there is any question
about the ingredients in a medication. Over-thecounter remedies containing phenylpropanolamine
should be discarded.



appetite suppressants



other medicine for colds, sinus problems, hay fever
or other allergies



beta-blockers such as atenolol (Tenormin) and
propranolol (Inderal)

Resources

digitalis glycosides, used to treat heart conditions

PERIODICALS



The list above does not include every drug that
may interact with decongestants. Be sure to check with
a physician or pharmacist before combining decongestants with any other prescription or nonprescription
(over-the-counter) medicine.

Description
Decongestants are sold in many forms, including
tablets, capsules, caplets, gelcaps, liqui-caps, liquids,
nasal sprays, and nose drops. These drugs are sometimes combined with other medicines in cold and
allergy products designed to relieve several symptoms.
Some decongestant products require a physician’s prescription, but there are also many nonprescription
(over-the-counter) products. Ask a physician or pharmacist about choosing an appropriate decongestant.
Commonly used decongestants include oxymetazoline (Afrin and other brands) and pseudoephedrine
(Sudafed, Actifed, and other brands). The decongestant oxymetazoline is also used in some eye drops to
relieve redness and itching.
The recommended dosage depends on the drug.
Check with the physician who prescribed the drug or
the pharmacist who filled the prescription for the correct
dosage, and always take the medicine exactly as directed.
If using nonprescription (over-the-counter) types, follow
the directions on the package label or ask a pharmacist
for assistance. Never take larger or more frequent doses,
and do not take the drug for longer than directed.

Risks
Anyone considering taking a decongestant should
take a close look at the labels of any already in their
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
The desired result when taking decongestants is
the short-term relief of nasal congestion.

Henderson, Charles W. ‘‘Voluntary Withdrawal of Cold and
Allergy Products Announced.’’ Medical Letter on the
CDC and FDA, November 26, 2000.
‘‘An Ingredient Under Fire: Drugmakers are Jittery Afteran
FDA Panel Ruling.’’ Newsweek, October 30, 2000: 59.
OTHER

Medline Plus Health Information. U.S.National Library of
Medicine. <http://www.nlm.nih.gov/medlineplus>.

Deanna M. Swartout-Corbeil, R.N.

Decubitus ulcers see Bedsores

I Deep vein thrombosis
Definition
Deep vein thrombosis (DVT) is a blood clot in a
major vein, usually in the legs and/or pelvis.

Description
Deep vein thrombosis is a common but difficult to
detect illness that can be fatal if not treated effectively.
According to the American Heart Association, more
than two million Americans develop deep vein thrombosis annually. An estimated 600,000 of these develop
pulmonary embolism, a potentially fatal complication
where the blood clots break off and form pulmonary
emboli, plugs that block the lung arteries. Sixty thousand people die of pulmonary embolism each year.
Deep vein thrombosis is also called venous thromboembolism, thrombophlebitis or phlebothrombosis.
1117

Deep vein thrombosis

KEY TERMS

Deep vein thrombosis

Deep vein thrombosis is a major complication in
patients who have had orthopedic surgery or pelvic,
abdominal, or thoracic surgery. Patients with cancer
and other chronic illnesses (including congestive heart
failure), as well as those who have suffered a recent
myocardial infarction, are also at high risk for developing DVT. Deep vein thrombosis can be chronic,
with recurrent episodes.

Causes and symptoms
Deep vein thrombosis is caused by blood clots in
blood vessels that form in veins where blood flow is
sluggish or has been disturbed, in pockets in the calf’s
deep veins, or in veins that have been traumatized.
Symptoms include swelling and tenderness of the calf
or thigh, and possibly warmth. Only 23–50% of
patients experience symptoms, so it’s often ‘‘silent.’’
Some individuals and families have underlying clotting tendencies that can be tested for.

Diagnosis
Deep vein thrombosis can be detected through
venography and radionuclide venography, Doppler
ultrasonography, and impedance plethysmography.
Venography is the most accurate test, but it is not
used much, because it is often painful, expensive,
exposes the patient to radiation, and can cause reactions and complications. Venography identifies the
location, extent, and degree of attachment of the
blood clots, and enables the condition of the deep
leg veins to be assessed. A contrast solution is
injected into a foot vein through a catheter. The
physician observes the movement of the solution
through the vein with a fluoroscope while a series
of x rays are taken. Venography takes 30–45 minutes
and can be done in a physician’s office, a laboratory,
or a hospital. Radionuclide venography, in which a
radioactive isotope is injected, is occasionally used,
especially if a patient has had reactions to contrast
solutions.
Doppler ultrasonography is usually the preferred
procedure for detecting deep vein thrombosis. This
technique uses sound waves to measure blood flow
through leg veins and arteries. A blood pressure cuff
is wrapped around the patient’s ankle and a transducer with gel on it is placed over pulse points of the
foot and lower leg. High-frequency sounds bounce
off the soft tissue, and the echoes are converted into
images on a monitor. It is very accurate in detecting
clots above the knee that can become pulmonary
embolisms. Usually performed in a physician’s office
1118

This illustration features a dissected human lower leg
showing clot formation (thrombosis) along the length of a
vein. (Custom Medical Stock Photo. Reproduced by permission.)

or hospital outpatient diagnostic center, Doppler
ultrasound usually takes 30–45 minutes.
Impedance plethysmography records changes in
blood volume and vessel resistance. A blood pressure
cuff is wrapped around the leg above the knee, four
electrodes are placed near the knee and the ankle, and
the cuff is inflated. How efficiently the veins return to
normal is measured. Performed in a physician’s office,
it takes about 15 minutes.

Treatment
Deep vein thrombosis can be treated with drug
therapy, bed rest, and gradient elastic stockings.
Medications include anticoagulants that ‘‘thin’’
blood to prevent further growth of blood clots, as
well as clot-dissolving drugs. Heparin is a common
injectable anticoagulant, and is usually followed by
GALE ENCYCLOPEDIA OF MEDICINE

Pulmonary embolism—An obstruction of a blood
vessel in the lungs, usually caused by a blood clot
that blocks a coronary artery. Pulmonary embolism
can be very serious and, in some cases, fatal.
Thrombosis—The development of a blood clot
inside a blood vessel.

Definition
Defibrillation is a process in which an electronic
device sends an electric shock to the heart to stop an
extremely rapid, irregular heartbeat, and restore the
normal heart rhythm.

Purpose
coumadin tablets for at least three months. Bed rest
with the patient’s legs elevated is necessary until the
condition improves. Gradient elastic stockings should
then be worn, and standing for long periods of time
avoided. In some cases, a filter is placed in the major
vein (the inferior vena cava) to trap emboli or clots
before they get to the heart and lungs.

Defibrillation is performed to correct lifethreatening fibrillations of the heart, which could
result in cardiac arrest. It should be performed immediately after identifying that the patient is experiencing a cardiac emergency, has no pulse, and is
unresponsive.

Precautions
Alternative treatment
Deep vein thrombosis can be life-threatening and
must be treated with conventional medical therapies.
However, there are alternative therapies that can be
used in conjunction with emergency treatments to dissolve the clot that help support the body and prevent
recurrence. A trained alternative health care practitioner should be consulted due to the severity of this
condition.

Prognosis
In many cases, deep vein thrombosis can be successfully treated if diagnosed early.

Prevention
Deep vein thrombosis can be prevented through
prophylactic anticoagulant drugs and venous stasis
prevention with gradient elastic stockings and intermittent pneumatic compression of the legs. High-risk
patients often need to remain on anticoagulants like
Coumadin indefinitely.
Resources
PERIODICALS

Davidson, Bruce L., and Eric J. Deppert. ‘‘Ultrasound for
the Diagnosis of Deep Vein Thrombosis: Where to
Now?’’ British Medical Journal 316 (January 3, 1998): 2.

Lori De Milto

Deer-fly fever see Tularemia
GALE ENCYCLOPEDIA OF MEDICINE

Defibrillation should not be performed on a
patient who has a pulse or is alert, as this could cause
a lethal heart rhythm disturbance or cardiac arrest.
The paddles used in the procedure should not be
placed on a woman’s breasts or over a pacemaker.

Description
Fibrillations cause the heart to stop pumping
blood, leading to brain damage and/or cardiac
arrest. About 10% of the ability to restart the heart
is lost with every minute that the heart stays in fibrillation. Death can occur in minutes unless the normal
heart rhythm is restored through defibrillation.
Because immediate defibrillation is crucial to the
patient’s survival, the American Heart Association
has called for the integration of defibrillation into an
effective emergency cardiac care system. The system
should include early access, early cardiopulmonary
resuscitation, early defibrillation, and early advanced
cardiac care.
Defibrillators deliver a brief electric shock to the
heart, which enables the heart’s natural pacemaker to
regain control and establish a normal heart rhythm. The
defibrillator is an electronic device with electrocardiogram leads and paddles. During defibrillation, the paddles are placed on the patient’s chest, caregivers stand
back, and the electric shock is delivered. The patient’s
pulse and heart rhythm are continually monitored.
Medications to treat possible causes of the abnormal
heart rhythm may be administered. Defibrillation continues until the patient’s condition stabilizes or the procedure is ordered to be discontinued.
1119

Defibrillation

I Defibrillation

KEY TERMS

Dehydration

Aftercare
After defibrillation, the patient’s cardiac status,
breathing, and vital signs are monitored until he or
she is stable. Typically, this monitoring takes place
after the patient has been removed to an intensive
care or cardiac care unit in a hospital. An electrocardiogram and chest x ray are taken. The patient’s skin is
cleansed to remove gel or paste, and, if necessary,
ointment is applied to burns. An intravenous line provides additional medication, as needed.

Risks
Defibrillation by paddles. (Photograph by Patricia Barber, RBP,
Custom Medical Stock Photo. Reproduced by permission.)

KEY TERMS
Cardiac arrest—A condition in which the heart
stops functioning. Fibrillation can lead to cardiac
arrest if not corrected quickly.

Skin burns from the defibrillator paddles are the
most common complication of defibrillation. Other
risks include injury to the heart muscle, abnormal
heart rhythms, and blood clots.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Fibrillation—Very rapid contractions or twitching
of small muscle fibers in the heart.
Pacemaker—A surgically implanted electronic
device that sends out electrical impulses to regulate
a slow or erratic heartbeat.

Lori De Milto

Definitive cancer therapy see Cancer therapy,
definitive
Degenerative arthritis see Osteoarthritis

Early defibrillators, about the size and weight of a
car battery, were used primarily in ambulances and
hospitals. The American Heart Association now advocates public access defibrillation; this calls for placing
automated external defibrillators (AEDS) in police
vehicles, airplanes, and at public events, etc. The
AEDS are smaller, lighter, less expensive, and easier
to use than the early defibrillators. They are computerized to provide simple, verbal instructions to the
operator and to make it impossible to deliver a shock
to a patient whose heart is not fibrillating. The placement of AEDs is likely to expand to many public
locations.

Preparation
After help is called for, cardiopulmonary resuscitation (CPR) is begun and continued until the caregivers
arrive and set up the defibrillator. Electrocardiogram
leads are attached to the patient’s chest. Gel or paste is
applied to the defibrillator paddles, or two gel pads are
placed on the patient’s chest. The caregivers verify lack
of a pulse, and select a charge.
1120

I Dehydration
Definition
Dehydration is the loss of water and salts essential
for normal body function.

Description
Dehydration occurs when the body loses more fluid
than it takes in. This condition can result from illness; a
hot, dry climate; prolonged exposure to sun or high
temperatures; not drinking enough water; and overuse
of diuretics or other medications that increase urination. Dehydration can upset the delicate fluid-salt balance needed to maintain healthy cells and tissues.
Water accounts for about 60% of a man’s body
weight. It represents about 50% of a woman’s weight.
Young and middle-aged adults who drink when
GALE ENCYCLOPEDIA OF MEDICINE

long, not drinking enough fluids, and visiting or moving to a warm region where it doesn’t often rain.
Alcohol, caffeine, and diuretics or other medications
that increase the amount of fluid excreted can cause
dehydration.
Reduced fluid intake can be a result of:

Age and dehydration
Adults over the age of 60 who drink only when
they are thirsty probably get only about 90% of the
fluid they need. Developing a habit of drinking only in
response to the body’s thirst signals raises an older
person’s risk of becoming dehydrated. Seniors who
have relocated to areas where the weather is warmer
or dryer than the climate they are accustomed to are
even likelier to become dehydrated unless they make it
a practice to drink even when they are not thirsty.
Dehydration in children usually results from losing large amounts of fluid and not drinking enough
water to replace the loss. This condition generally
occurs in children who have stomach flu characterized
by vomiting and diarrhea, or who can not or will not
take enough fluids to compensate for excessive losses
associated with fever and sweating of acute illness. An
infant can become dehydrated only hours after
becoming ill. Dehydration is a major cause of infant
illness and death throughout the world.
Types of dehydration
Mild dehydration is the loss of no more than 5%
of the body’s fluid. Loss of 5–10% is considered
moderate dehydration. Severe dehydration (loss of
10–15% of body fluids) is a life-threatening condition
that requires immediate medical care.
Complications of dehydration
When the body’s fluid supply is severely depleted,
hypovolemic shock is likely to occur. This condition,
which is also called physical collapse, is characterized
by pale, cool, clammy skin; rapid heartbeat; and shallow breathing.
Blood pressure sometimes drops so low it can not
be measured, and skin at the knees and elbows may
become blotchy. Anxiety, restlessness, and thirst
increase. After the patient’s temperature reaches
107 8F (41.7 8C) damage to the brain and other vital
organs occurs quickly.

Causes and symptoms
Strenuous activity, excessive sweating, high fever,
and prolonged vomiting or diarrhea are common
causes of dehydration. So are staying in the sun too
GALE ENCYCLOPEDIA OF MEDICINE



appetite loss associated with acute illness



excessive urination (polyuria)



nausea



bacterial or viral infection or inflammation of the
pharynx (pharyngitis)



inflammation of the mouth caused by illness, infection, irritation, or vitamin deficiency (stomatitis)

Other conditions that can lead to dehydration
include:


disease of the adrenal glands, which regulate the
body’s water and salt balance and the function of
many organ systems



diabetes mellitus



eating disorders



kidney disease



chronic lung disease.

An infant who does not wet a diaper in an eighthour period is dehydrated. The soft spot on the baby’s
head (fontanel) may be depressed. Symptoms of dehydration at any age include cracked lips, dry or sticky
mouth, lethargy, and sunken eyes. A person who is
dehydrated cries without shedding tears and does not
urinate very often. The skin is less elastic than it should
be and is slow to return to its normal position after
being pinched.
Dehydration can cause confusion, constipation,
discomfort, drowsiness, fever, and thirst. The skin
turns pale and cold, the mucous membranes lining
the mouth and nose lose their natural moisture. The
pulse sometimes races and breathing becomes rapid.
Significant fluid loss can cause serious neurological
problems.

Diagnosis
The patient’s symptoms and medical history
usually suggest dehydration. Physical examination
may reveal shock, rapid heart rate, and/or low blood
pressure. Laboratory tests, including blood tests (to
check electrolyte levels) and urine tests (e.g., urine
specific gravity and creatinine), are used to evaluate
the severity of the problem. Other laboratory tests
may be ordered to determine the underlying condition
1121

Dehydration

they’re thirsty do not generally have to do anything
more to maintain their body’s fluid balance. Children
need more water because they expend more energy,
but most children who drink when they are thirsty get
as much water as their systems require.

Dehydration

(such as diabetes or an adrenal gland disorder) causing
the dehydration.

Treatment
Increased fluid intake and replacement of lost
electrolytes are usually sufficient to restore fluid balances in patients who are mildly or moderately dehydrated. For individuals who are mildly dehydrated,
just drinking plain water may be all the treatment
that is needed. Adults who need to replace lost electrolytes may drink sports beverages (e.g., Gatorade
or Recharge) or consume a little additional salt.
Parents should follow label instructions when giving
children Pedialyte or other commercial products
recommended to relieve dehydration. Children who
are dehydrated should receive only clear fluids for the
first 24 hours.
A child who is vomiting should sip one or two
teaspoons of liquid every 10 minutes. A child who is
less than a year old and who is not vomiting should be
given one tablespoon of liquid every 20 minutes. A
child who is more than one year old and who is not
vomiting should take two tablespoons of liquid every
30 minutes. A baby who is being breast-fed should be
given clear liquids for two consecutive feedings
before breastfeeding is resumed. A bottle-fed baby
should be given formula diluted to half its strength
for the first 24 hours after developing symptoms of
dehydration.
In order to accurately calculate fluid loss, it’s
important to chart weight changes every day and
keep a record of how many times a patient vomits or
has diarrhea. Parents should note how many times a
baby’s diaper must be changed.
Children and adults can gradually return to their
normal diet after they have stopped vomiting and no
longer have diarrhea. Bland foods should be reintroduced first, with other foods added as the digestive
system is able to tolerate them. Milk, ice cream,
cheese, and butter should not be eaten until 72 hours
after symptoms have disappeared.
Medical care
Severe dehydration can require hospitalization
and intravenous fluid replacement. If an individual’s
blood pressure drops enough to cause or threaten the
development of shock, medical treatment is usually
required. A doctor should be notified whenever an
infant or child exhibits signs of dehydration or a parent is concerned that a stomach virus or other acute
illness may lead to dehydration.
1122

a doctor should also be notified if:


a child less than three months old develops a fever
higher than 100 8F (37.8 8C)



a child more than three months old develops a fever
higher than 102 8F (38.9 8C)



symptoms of dehydration worsen



an individual urinates very sparingly or does not
urinate at all during a six-hour period



dizziness, listlessness, or excessive thirst occur



a person who is dieting and using diuretics loses more
than 3 lb (1.3 kg) in a day or more than 5 lb (2.3 kg) a
week

When treating dehydration, the underlying cause
must also be addressed. For example, if dehydration is
caused by vomiting or diarrhea, medications may be
prescribed to resolve these symptoms. Patients who
are dehydrated due to diabetes, kidney disease, or
adrenal gland disorders must receive treatment for
these conditions as well as for the resulting
dehydration.

Alternative treatment
Gelatin water can be substituted for electrolytereplacement solutions. It is made by diluting a 3-oz
package in a quart of water or by adding one-quarter
teaspoon of salt and a tablespoon of sugar to a pint of
water.

Prognosis
Mild dehydration rarely results in complications.
If the cause is eliminated and lost fluid is replaced,
mild dehydration can usually be cured in 24–48 hours.
Vomiting and diarrhea that continue for several
days without adequate fluid replacement can be fatal.
The risk of life-threatening complications is greater for
young children and the elderly. However, dehydration
that is rapidly recognized and treated has a good
outcome.

Prevention
Patients who are vomiting or who have diarrhea
can prevent dehydration by drinking enough fluid for
their urine to remain the color of pale straw. Ensuring
that patients always drink adequate fluids during an
illness will help prevent dehydration. Infants and
young children with diarrhea and vomiting can be
given electrolyte solutions such as Pedialyte to help
prevent dehydration. People who are not ill can
GALE ENCYCLOPEDIA OF MEDICINE

Electrolytes—Mineral salts, such as sodium and
potassium, dissolved in body fluid.

maintain proper fluid balance by drinking several
glasses of water before going outside on a hot day. It
is also a good idea to avoid coffee and tea, which
increase body temperature and water loss.

T cells. Both these immune agents respond when the
body is reexposed to the antigen. Antibodies, which
are circulating proteins, respond within minutes, to
give what, is termed an immediate hypersensitivity
reaction. T cells responses occur over several days,
and are thus called delayed hypersensitivity reactions.
The cascade of events initiated by the T cells leads to
hardening (induration) and redness (erythema) at the
injection site.
A DHT is performed for one of three reasons:


To test for exposure to specific diseases, such as
tuberculosis (TB). Tuberculosis testing is done by
injecting into the skin a small volume of TB antigen,
which contains no organisms (live or dead) but can
still provoke an immune response.



To test for allergic sensitivity to potential skin irritants, such as poison ivy. Skin allergy testing is
usually done by placing a series of adhesive patches
on the skin containing potential allergens, or allergycausing substances.



To assess the vitality of the T cell response as part of
the evaluation of immune system health in infection,
cancer, immune disorders, pre-transplantation
screening, aging, and malnutrition. DHT can help
predict survival in immunocompromised patients,
and evaluate the success of restorative therapy.
Antigens used for these tests must be ones the patient
has been exposed to before, and, therefore, include
inactivated antigens from common infectious agents
to which the patient might have been exposed, such
as mumps, Candida albicans, tetanus toxoid, and
trichophyton (a skin fungus).

Patients should know whether any medication
they are taking can cause dehydration and should get
prompt medical care to correct any underlying condition that increases the risk of dehydration.
Other methods of preventing dehydration and
ensuring adequate fluid intake include:


eating more soup at mealtime



drinking plenty of water and juice at mealtime and
between meals



keeping a glass of water nearby when working or
relaxing

Resources
OTHER

‘‘Hydration—Getting Enough Water.’’ Loyola University
Health System. May 13, 1998. <http://
www.luhs.org>.

Maureen Haggerty

Delavirdine see Non-nucleoside reverse
transcriptase inhibitors

hypersensitivity skin
I Delayed
test

Precautions
No special precautions are necessary for most
patients. Those with known hypersensitivity to certain
skin irritants should alert the clinician performing the
test. Some commercial preparations of fungal antigens
contain mercury, a source of irritation to some
patients.

Definition
A delayed hypersensitivity test (DHT) is an
immune function test measuring the presence of activated T cells that recognize a certain substance.

Purpose
The immune system protects against infection by
viruses, bacteria, fungi, and parasites. After initial
exposure to a foreign substance, or antigen, the
immune system creates both antibodies and sensitized
GALE ENCYCLOPEDIA OF MEDICINE

Description
The most accurate TB test is the Mantoux test, in
which a small amount of TB antigen is injected into the
skin. The area is examined 48–72 hours after the
injection.
In the patch test, 20–30 adhesive patches are
usually placed on the upper back. The patches are
kept in place and the area is kept dry for 48 hours.
The patches are then removed, and the skin is
1123

Delayed hypersensitivity skin test

KEY TERMS

Delirium

examined 24 hours afterward, and possibly again a
day or more following that. Patch testing is usually
performed following a patient complaint of skin irritation from an unknown substance. Testing may suggest
several candidates; identifying the right one requires
careful review of the patient’s possible exposure.
The test of overall T cell responsiveness is performed with several injections. Each area injected is
circled and marked. Results are read 48 hours after the
injection.

Preparation
No special preparation is necessary.

Aftercare
Patches should be kept dry. Injection sites may be
washed, but excessive rubbing should be avoided.
Patches and injection sites may become reddened or
irritated. If a patch causes severe itching or discomfort, the patient should remove it immediately.

Risks
DHT is quite safe for virtually all people. There is
no risk of infection from the agents injected, since
they are purified antigens, not whole organisms. Life
threatening, hypersensitive reactions (anaphylaxis)
are a very small risk; patients should notify the
administering physician immediately if signs of
wheezing, swelling, or diffuse redness of the skin
develops.

KEY TERMS
Allergen—A foreign substance that provokes an
immune reaction in some sensitive people but not
in most others.
Anaphylaxis—An exaggerated, life-threatening
hypersensitivity reaction to a previously encountered antigen.
Antibody—An immune system protein made to
fight infection.
Antigen—A foreign substance detected that provokes an immune reaction.

Patch test areas that become reddened and irritated indicate reaction to the substance in the patch.
Absence of any reaction to injected areas indicates
lack of T cell responsiveness, a condition called
anergy. T cell anergy is seen in immune deficiency
diseases including AIDS, some cases of infectious diseases, malignancies, immunosuppressive therapy
(including corticosteroid treatment), some autoimmune diseases, malnutrition, major surgery, and
some viral immunizations.
Resources
BOOKS

Lawlor Jr., G. J., et. al. Manual of Allergy and Immunology.
Little, Brown and Co., 1995.

Richard Robinson

Normal results
Absence of exposure to TB is indicated by absent
or very little skin reaction; redness or hardness smaller
than 5 mm (about 0.25 in) is considered normal for a
person not exposed or infected with TB.
Patch test sites should be normal or only
slightly red.
T cell responsiveness tests should be positive; that
is, the injected areas should be reddened and hard.
Two affected areas of 2 mm or more is considered a
positive result.

Abnormal results
TB exposure is indicated by a reaction of 10 mm
or more. The degree of redness is not important. A
5–10 mm area could indicate exposure if there is an
underlying risk to TB.
1124

I Delirium
Definition
Delirium is a state of mental confusion that develops quickly and usually fluctuates in intensity.

Description
Delirium is a syndrome, or group of symptoms,
caused by a disturbance in the normal functioning of
the brain. The delirious patient has a reduced awareness of and responsiveness to the environment, which
may be manifested as disorientation, incoherence, and
memory disturbance. Delirium is often marked by
hallucinations, delusions, and a dream-like state.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Causes
There are a large number of possible causes of
delirium. Metabolic disorders are the single most common cause, accounting for 20–40% of all cases. This
type of delirium, termed ‘‘metabolic encephalopathy,’’
may result from organ failure, including liver or kidney
failure. Other metabolic causes include diabetes mellitus, hyperthyroidism and hypothyroidism, vitamin deficiencies, and imbalances of fluids and electrolytes in the
blood. Severe dehydration can also cause delirium.
Drug intoxication (‘‘intoxication confusional
state’’) is responsible for up to 20% of delirium
cases, either from side effects, overdose, or deliberate
ingestion of a mind-altering substance. Medicinal
drugs with delirium as a possible side effect or result
of overdose include:


anticholinergics, including atropine, scopolamine,
chlorpromazine (an antipsychotic), and diphenhydramine (an antihistamine)



amphetamines



cocaine



opiates, including heroin and morphine



PCP (phencyclidine)



inhalants

Drug withdrawal may also cause delirium.
Delirium tremens, or ‘‘DTs,’’ may occur during alcohol withdrawal after prolonged or intense consumption. Withdrawal symptoms are also possible from
many of the psychoactive prescription drugs.
Poisons may cause delirium (‘‘toxic encephalopathy’’), including:


solvents, such as gasoline, kerosene, turpentine,
benzene, and alcohols



carbon monoxide



refrigerants (Freon)



heavy metals, such as lead, mercury, and arsenic



insecticides, such as Parathion and Sevin



mushrooms, such as Amanita species



plants such as jimsonweed (Datura stramonium) and
morning glory (Ipomoea spp.)



animal venoms
Other causes of delirium include:



infection

sedatives, including barbiturates, benzodiazepines,
and ethanol (drinking alcohol)



fever



head trauma



antidepressant drugs



epilepsy



anticonvulsant drugs



brain hemorrhage or infarction



nonsteroidal anti-inflammatory drugs (NSAIDs),
including ibuprofen and acetaminophen



brain tumor



low blood oxygen (hypoxemia)



corticosteroids, including prednisone



high blood carbon dioxide (hypercapnia)



anticancer drugs, including methotrexate and
procarbazine



post-surgical complication



lithium



cimetidine



antibiotics



L-dopa



Delirium

Delirium affects at least one in 10 hospitalized
patients, and is a common part of many terminal illnesses. Delirium is more common in the elderly than in
the general population. While it is not a specific disease itself, patients with delirium usually fare worse
than those with the same illness who do not have
delirium.

Symptoms

Delirium may result from ingestion of legal or
illegal psychoactive drugs, including:


ethanol (drinking alcohol)



marijuana



LSD (lysergic
hallucinogens

acid

diethylamide)

and

GALE ENCYCLOPEDIA OF MEDICINE

other

The symptoms of delirium come on quickly, in
hours or days, in contrast to those of dementia,
which develop much more slowly. Delirium symptoms
typically fluctuate through the day, with periods of
relative calm and lucidity alternating with periods of
florid delirium. The hallmark of delirium is a fluctuating level of consciousness. Symptoms may include:


decreased awareness of the environment



confusion or disorientation, especially of time



memory impairment, especially of recent events
1125

Delusions

Prognosis

KEY TERMS
Dementia—A loss of mental ability severe enough
to interfere with functioning. While dementia and
delirium have some of the same symptoms, dementia has a much slower onset.
Electroencephalogram (EEG)— A chart of the brain
wave patterns picked up by electrodes placed on
the scalp. This is useful for diagnosing central
nervous system disorders.
Encephalopathy—A brain dysfunction or disorder.



hallucinations



illusions and misinterpreted stimuli



increased or decreased activity level



mood disturbance, possibly including anxiety,
euphoria or depression



language or speech impairment

Diagnosis
Delirium is diagnosed through the medical history and recognition of symptoms during mental
status examination. The most important part of
diagnosis is determining the cause of the delirium.
Tests may include blood and urine analysis for levels
of drugs, fluids, electrolytes, and blood gases, and to
test for infection; lumbar puncture (‘‘spinal tap’’) to
test for central nervous system infection; x ray, computed tomography scans (CT), or magnetic resonance
imaging (MRI) scans to look for tumors, hemorrhage,
or other brain abnormality; thyroid tests; electroencephalography (EEG); electrocardiography (ECG);
and possibly others as dictated by the likely cause.

Treatment
Treatment of delirium begins with recognizing
and treating the underlying cause. Delirium itself is
managed by reducing disturbing stimuli, or providing
soothing ones; use of simple, clear language in communication; and reassurance, especially from family
members. Physical restraints may be needed if the
patient is a danger to himself or others, or if he insists
on removing necessary medical equipment such as
intravenous lines or monitors. Sedatives or antipsychotic drugs may be used to reduce anxiety, hallucinations, and delusions.
1126

Persons with delirium usually have a worse prognosis for the underlying disease than the person without delirium. Nonetheless, those without terminal
illness usually recover from delirium. They may not,
however, regain all their original cognitive abilities,
and may be left with some permanent impairments,
including fatigue, irritability, difficulty concentrating,
or mood changes.

Prevention
Prevention of delirium is focused on treating or
avoiding its underlying causes. The most preventable
forms are those induced by drugs. Strategies for reducing delirium include following prescriptions, consulting the prescribing physician immediately if symptoms
occur, and consulting the physician before discontinuing the drug, even if it has been ineffective; avoiding
intoxication with legal or illegal drugs, and seeking
professional assistance before suddenly discontinuing
an addictive drug such as alcohol or heroin; maintaining good nutrition, which promotes general health and
can minimize the likelihood of delirium from alcohol
intoxication and withdrawal; and avoiding exposure
to solvents, insecticides, heavy metals, or biological
poisons in the home or workplace.
Resources
BOOKS

Guze, Samuel, editor. Adult Psychiatry. Mosby Year Book,
1997.

Richard Robinson

Delta virus hepatitis see Hepatitis D

I Delusions
Definition
A delusion is an unshakable belief in something
untrue. These irrational beliefs defy normal reasoning,
and remain firm even when overwhelming proof is
presented to dispute them. Delusions are often accompanied by hallucinations and/or feelings of paranoia,
which act to strengthen confidence in the delusion.
Delusions are distinct from culturally or religiously
based beliefs that may be seen as untrue by outsiders.
GALE ENCYCLOPEDIA OF MEDICINE

Delusions are a common symptom of several mood
and personality-related mental illnesses, including schizoaffective disorder, schizophrenia, shared psychotic disorder, major depressive disorder, and bipolar disorder.
They are also the major feature of delusional disorder.
Individuals with delusional disorder suffer from longterm, complex delusions that fall into one of six categories:
persecutory, grandiose, jealousy, erotomanic, somatic, or
mixed. There are also delusional disorders such as dementia that clearly have organic or physical causes.

KEY TERMS
Hallucinations—False or distorted sensory experiences that appear to be real perceptions.
Paranoia—An unfounded or exaggerated distrust of
others.
Shared psychotic disorder—Also known as folie
à deux; shared psychotic disorder is an uncommon
disorder in which the same delusion is shared by
two or more individuals.

Persecutory
Individuals with persecutory delusional disorder
are plagued by feelings of paranoia and an irrational
yet unshakable belief that someone is plotting against
them, or out to harm them.
Grandiose
Individuals with grandiose delusional disorder
have an inflated sense of self-worth. Their delusions
center on their own importance, such as believing that
they have done or created something of extreme value
or have a ‘‘special mission.’’
Jealousy
Jealous delusions are unjustified and irrational
beliefs that an individual’s spouse or significant other
has been unfaithful.
Erotomanic
Individuals with erotomanic delusional disorder
believe that another person, often a stranger, is in love
with them. The object of their affection is typically of a
higher social status, sometimes a celebrity. This type of
delusional disorder may lead to stalking or other
potentially dangerous behavior.
Somatic
Somatic delusions involve the belief that something is physically wrong with the individual. The
delusion may involve a medical condition or illness
or a perceived deformity. This condition differs from
hypochondriasis in that the deformity is perceived as a
fixed condition not a temporary illness.
Mixed
Mixed delusions are those characterized by two or
more of persecutory, grandiose, jealousy, erotomanic,
or somatic themes.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Some studies have indicated that delusions may be
generated by abnormalities in the limbic system, the
portion of the brain on the inner edge of the cerebral
cortex that is believed to regulate emotions. The exact
source of delusions has not been conclusively found, but
potential causes include genetics, neurological
abnormalities, and changes in brain chemistry.
Delusions are also a known possible side effect of drug
use and abuse (e.g., amphetamines, cocaine, PCP).

Diagnosis
Patients with delusional symptoms should
undergo a thorough physical examination and patient
history to rule out possible organic causes (such as
dementia). If a psychological cause is suspected, a
mental health professional will typically conduct an
interview with the patient and administer one of several clinical inventories, or tests, to evaluate mental
status.

Treatment
Delusions that are symptomatic of delusional disorder should be treated by a psychologist and/or psychiatrist. Though antipsychotic drugs are often not
effective, antipsychotic medication such as thioridazine (Mellaril), haloperidol (Haldol), chlorpromazine
(Thorazine), clozapine (Clozaril), or risperidone
(Risperdal) may be prescribed, and cognitive therapy
or psychotherapy may be attempted.
If an underlying condition such as schizophrenia,
depression, or drug abuse is found to be triggering the
delusions, an appropriate course of medication and/or
psychosocial therapy is employed to treat the primary
disorder. The medication, typically, will include an
antipsychotic agent.
1127

Delusions

Description

Dementia

Prognosis
Delusional disorder is typically a chronic condition, but with appropriate treatment, a remission of
delusional symptoms occurs in up to 50% of patients.
However, because of their strong belief in the reality of
their delusions and a lack of insight into their condition, individuals with this disorder may never seek
treatment, or may be resistant to exploring their condition in psychotherapy.
Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.

Estimates for dementia in those 85 and over range
from 30–47%. Between two and four million
Americans have AD; that number is expected to
grow to as many as 14 million by the middle of the
twenty-first century as the population ages.
The cost of dementia can be considerable. While
most people with dementia are retired and do not
suffer income losses from their disease, the cost of
care often is enormous. Financial burdens include
lost wages for family caregivers, medical supplies and
drugs, and home modifications to ensure safety.
Nursing home care may cost several thousand dollars
a month or more. The psychological cost is not as
easily quantifiable but can be even more profound.
The person with dementia loses control of many of
the essential features of his life and personality, and
loved ones lose a family member even as they continue
to cope with the burdens of increasing dependence and
unpredictability.

Causes and symptoms
Paula Anne Ford-Martin

I Dementia
Definition
Dementia is a loss of mental ability severe enough
to interfere with normal activities of daily living, lasting more than six months, not present since birth,
and not associated with a loss or alteration of
consciousness.

Description
Dementia is a group of symptoms caused by gradual death of brain cells. The loss of cognitive abilities
that occurs with dementia leads to impairments in
memory, reasoning, planning, and behavior. While
the overwhelming number of people with dementia
are elderly, it is not an inevitable part of aging.
Instead, dementia is caused by specific brain diseases.
Alzheimer’s disease (AD) is the most common cause,
followed by vascular or multi-infarct dementia.
The prevalence of dementia has been difficult to
determine, partly because of differences in definition
among different studies, and partly because there is
some normal decline in functional ability with age.
Dementia affects 5–8% of all people between ages 65
and 74, and up to 20% of those between 75 and 84.
1128

Causes
Dementia usually is caused by degeneration in the
cerebral cortex, the part of the brain responsible for
thoughts, memories, actions and personality. Death of
brain cells in this region leads to the cognitive impairment that characterizes dementia.
The most common cause of dementia is AD,
accounting for one-half to three-fourths of all cases.
The brain of a person with AD becomes clogged with
two abnormal structures, called neurofibrillary tangles and senile plaques. Neurofibrillary tangles are
twisted masses of protein fibers inside nerve cells, or
neurons. Senile plaques are composed of parts of neurons surrounding a group of proteins called beta-amyloid deposits. Why these structures develop is
unknown. Current research indicates possible roles
for inflammation, blood flow restriction, and toxic
molecular fragments known as free radicals. Several
genes have been associated with higher incidences of
AD, although the exact role of these genes still is
unknown.
Vascular dementia is estimated to cause from
5–30% of all dementias. It occurs from decrease in
blood flow to the brain, most commonly due to a series
of small strokes (multi-infarct dementia). Other cerebrovascular causes include: vasculitis from syphilis,
Lyme disease, or systemic lupus erythematosus; subdural hematoma; and subarachnoid hemorrhage.
Because of the usually sudden nature of its cause, the
symptoms of vascular dementia tend to begin more
GALE ENCYCLOPEDIA OF MEDICINE

Later, he or she may not understand his or her own
sentences, and have difficulty forming thoughts into
words.


Poor judgment. The person may not recognize the
consequences of his or her actions or be able to
evaluate the appropriateness of behavior. Behavior
may become rude, overly friendly, or aggressive.
Personal hygiene may be ignored.



Impaired orientation ability. The person may not be
able to identify the time of day, even from obvious
visual clues; or may not recognize his or her location,
even if familiar. This disability may stem partly from
losses of memory and partly from impaired
abstraction.



Decreased attention and increased restlessness. This
may cause the person with dementia to begin an
activity and quickly lose interest, and to wander
frequently. Wandering may cause significant safety
problems, when combined with disorientation and
memory losses. The person may begin to cook something on the stove, then become distracted and wander away while it is cooking.



Behavioral changes and psychosis. The person with
dementia may lose interest in once-pleasurable activities, and become more passive, depressed, or
anxious. Delusions, suspicion, paranoia, and hallucinations may occur later in the disease. Sleep disturbances may occur, including insomnia and sleep
interruptions.

Other conditions that may cause dementia
include:


AIDS



Parkinson’s disease



Lewy body disease



Pick’s disease



Huntington’s disease



Creutzfeldt-Jakob disease



brain tumor



hydrocephalus



head trauma



multiple sclerosis



prolonged abuse of alcohol or other drugs



vitamin deficiency: thiamin, niacin, or B12



hypothyroidism



hypercalcemia
Symptoms

Dementia is marked by a gradual impoverishment
of thought and other mental activities. Losses eventually affect virtually every aspect of mental life. The
slow progression of dementia is in contrast with delirium, which involves some of the same symptoms, but
has a very rapid onset and fluctuating course with
alteration in the level of consciousness. However,
delirium may occur with dementia, especially since
the person with dementia is more susceptible to the
delirium-inducing effects of may types of drugs.
Symptoms include:


Memory losses. Memory loss usually is the first
symptom noticed. It may begin with misplacing valuables such as a wallet or car keys, then progress to
forgetting appointments, where the car was left, and
the route home, for instance. More profound losses
follow, such as forgetting the names and faces of
family members.



Impaired abstraction and planning. The person with
dementia may lose the ability to perform familiar
tasks, to plan activities, and to draw simple conclusions from facts.



Language and comprehension disturbances. The
person may be unable to understand instructions,
or follow the logic of moderately complex sentences.

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Since dementia usually progresses slowly, diagnosing it in its early stages can be difficult. However,
prompt intervention and treatment has been shown to
help slow the effects of dementia, so early diagnosis is
important. Several office visits over several months or
more may be needed. Diagnosis begins with a thorough physical exam and complete medical history,
usually including comments from family members or
caregivers. A family history of either AD or cerebrovascular disease may provide clues to the cause of
symptoms. Simple tests of mental function, including
word recall, object naming, and number-symbol
matching, are used to track changes in the person’s
cognitive ability.
Depression is common in the elderly and can be
mistaken for dementia; therefore, ruling out depression is an important part of the diagnosis.
Distinguishing dementia from the mild normal cognitive decline of advanced age also is critical. The medical history includes a complete listing of drugs being
1129

Dementia

abruptly than those of Alzheimer’s dementia.
Symptoms may progress stepwise with the occurrence
of new strokes. Unlike AD, the incidence of vascular
dementia is lower after age 75.

Dementia

taken, since a number of drugs can cause dementialike symptoms.
Determining the cause of dementia may require a
variety of medical tests, chosen to match the most
likely etiology. Cerebrovascular disease, hydrocephalus, and tumors may be diagnosed with x rays, CT or
MRI scans, and vascular imaging studies. Blood tests
may reveal nutritional deficiencies or hormone
imbalances.

Treatment
Treatment of dementia begins with treatment of
the underlying disease, where possible. The underlying
causes of nutritional, hormonal, tumor-caused and
drug-related dementias may be reversible to some
extent. Treatment for stroke-related dementia begins
by minimizing the risk of further strokes, through
smoking cessation, aspirin therapy, and treatment of
hypertension, for instance. No therapies can reverse
the progression of AD. Aspirin, estrogen, vitamin E,
and selegiline have been evaluated for their ability to
slow the rate of progression. However, none of these
have been proven effective. In fact, in 2002 and 2003,
research revealed that non-steroidal anti-inflammatory agents (NSAIDs) did not help prevent AD and
dementia. In the same two years, the Women’s Health
Initiative, a large clinical trial, was halted because of
detrimental effects of combined estrogen and progestigin therapy, or hormone replacement therapy (HRT).
Not only was HRT found to increase risk of breast
cancer, stroke, and other heart disease, but the risk of
probable dementia was twice that for women taking
HRT than for those taking a placebo. Further, those
taking HRT had a substantial and clinically important
decline in indicators of cognitive ability. Studies still
debate the effects of vitamin E on slowing the progression of moderately severe AD.
Care for a person with dementia can be difficult
and complex. The patient must learn to cope with
functional and cognitive limitations, while family
members or other caregivers assume increasing
responsibility for the person’s physical needs. In progressive dementias such as AD, the person may ultimately become completely dependent. Education of
the patient and family early in the disease progression
can help them anticipate and plan for inevitable
changes.
Symptoms of dementia may be treated with a
combination of psychotherapy, environmental modifications, and medication. Drug therapy can be complicated by forgetfulness, especially if the prescribed
drug must be taken several times daily.
1130

Behavioral approaches may be used to reduce the
frequency or severity of problem behaviors, such as
aggression or socially inappropriate conduct. Problem
behavior may be a reaction to frustration or overstimulation; understanding and modifying the situations that trigger it can be effective. Strategies may
include breaking down complex tasks, such as dressing
or feeding, into simpler steps, or reducing the amount
of activity in the environment to avoid confusion and
agitation. Pleasurable activities, such as crafts, games,
and music, can provide therapeutic stimulation and
improve mood.
Modifying the environment can increase safety
and comfort while decreasing agitation. Home modifications for safety include removal or lock-up of
hazards such as sharp knives, dangerous chemicals,
and tools. Child-proof latches or Dutch doors may
be used to limit access as well. Lowering the hot
water temperature to 120 8F (48.9 8C) or less reduces
the risk of scalding. Bed rails and bathroom safety
rails can be important safety measures, as well.
Confusion may be reduced with simpler decorative
schemes and presence of familiar objects. Covering
or disguising doors (with a mural, for example) may
reduce the tendency to wander. Positioning the bed in
view of the bathroom can decrease incontinence.
Two drugs, tacrine (Cognex) and donepezil
(Aricept), are commonly prescribed for AD. These
drugs inhibit the breakdown of acetylcholine in the
brain, prolonging its ability to conduct chemical messages between brain cells. They provide temporary
improvement in cognitive functions for some patients
with mild to moderate AD and help delay disease
progression.
Psychotic symptoms, including paranoia, delusions,
and hallucinations, may be treated with antipsychotic
drugs, such as haloperidol, chlorpromazine, risperidone, and clozapine. Side effects of these drugs can be
significant. Antianxiety drugs such as Valium may
improve behavioral symptoms, especially agitation and
anxiety, although BuSpar has fewer side effects. The
anticonvulsant carbamazepine also is sometimes prescribed for agitation. Depression is treated with antidepressants, usually beginning with selective serotonin
reuptake inhibitors (SSRIs) such as Prozac or Paxil,
followed by monoamine oxidase inhibitors or tricyclic
antidepressants. In general, medications should be
administered cautiously to demented patients, in the
lowest possible effective doses, to minimize side effects.
Supervision of taking medications is generally required.
Long-term institutional care may be needed for the
person with dementia, as profound cognitive losses
GALE ENCYCLOPEDIA OF MEDICINE

Family members or others caring for a person
with dementia often are subject to extreme stress,
and may develop feelings of anger, resentment, guilt,
and hopelessness, in addition to the sorrow they feel
for their loved one and for themselves. Depression is
an extremely common consequence of being a fulltime caregiver for a person with dementia. Support
groups can be an important way to deal with the stress
of caregiving. The location and contact numbers for
caregiver support groups are available from the
Alzheimer’s Association; they may also be available
through a local social service agency or the patient’s
physician. Medical treatment for depression may be
an important adjunct to group support.

Alternative treatment
Several drugs are currently being tested for their
ability to slow the progress of AD. These include
acetyl-l-carnitine, which acts on the cellular energy
structures known as mitochondria; propentofylline,
which may aid circulation; milameline, which acts
similarly to tacrine and donezepil; and ginkgo extract.
Ginkgo extract, derived from the leaves of the Ginkgo
biloba tree, interferes with a circulatory protein called
platelet activating factor. It also increases circulation
and oxygenation to the brain. Ginkgo extract has been
used for many years in China and is widely prescribed in
Europe for treatment of circulatory problems. A 1997
study of patients with dementia seemed to show that
gingko extract could improve their symptoms, though
the study was criticized for certain flaws in its method.

Prognosis
The prognosis for dementia depends on the underlying disease. On average, people with Alzheimer’s disease live eight years past their diagnosis, with a range from
one to 20 years. Vascular dementia usually is progressive,
with death from stroke, infection, or heart disease.

Prevention
There is no known way to prevent Alzheimer’s
disease, although several drugs under investigation
may reduce its risk or slow its progression. The risk
of developing multi-infarct dementia may be reduced
by reducing the risk of stroke. Various studies
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Donepezil—A drug commonly prescribed for
Alzheimer’s disease that provides temporary
improvement in cognitive functions for some
patients with mild-to-moderate forms of the disease.
Ginkgo extract—Made from the leaves of the
Ginkgo biloba tree, this extract, used in other countries to treat circulatory problems, may improve the
symptoms of patients with dementia.
Neurofibrillary tangles—Abnormal structures,
composed of twisted masses of protein fibers within
nerve cells, found in the brains of people with
Alzheimer’s disease.
Senile plaques—Abnormal structures, composed of
parts of nerve cells surrounding protein deposits,
found in the brains of people with Alzheimer’s disease.
Tacrine—A drug commonly prescribed for
Alzheimer’s disease that provides temporary
improvement in cognitive functions for some
patients with mild-to-moderate forms of the disease.

continue to determine ways to lower risk of AD and
dementia. For example, a 2003 study in the New
England Journal of Medicine reported that people
over age 75 who participated in leisure activities such
as playing board games, reading, dancing, and playing
musical instruments were less likely to have dementia
after five years than others their age.
Resources
PERIODICALS

‘‘Antioxidants Don’t Prevent Dementia.’’ JAAPA —
Journal of the American Academy of Physicians
Assistants, May 2003: 25.
MacReady, Norra. ‘‘Prompt Intervention May Help Slow
Dementia.’’ Clinical Psychiatry News, May 2003: 38.
‘‘Research Breifs: Play Keeps Dementia Away.’’ GP, June
23, 2003: 04.
‘‘Risks of Hormone Treatment.’’ The Lancet, May 31, 2003:
1877.
ORGANIZATIONS

Alzheimer’s Association. 919 North Michigan Ave., Suite
1000, Chicago, IL 60611. (800) 272-3900. <http://
www.alz.org>.

Richard Robinson
Teresa G. Odle

Demyelinating disease see Multiple sclerosis
1131

Dementia

often precede death by a number of years. Early planning for the financial burden of nursing home care is
critical. Useful information about financial planning for
long-term care is available through the Alzheimer’s
Association.

Dengue fever

I Dengue fever
Definition
Dengue fever is a disease caused by one of a number of viruses that are carried by mosquitoes. These
mosquitoes then transmit the virus to humans.

Description
The virus that causes dengue fever is called an
arbovirus, which stands for arthropod-borne virus.
Mosquitoes are a type of arthropod. In a number of
regions, mosquitoes carry this virus and are responsible for passing it along to humans. These regions
include the Middle East, the far East, Africa, and the
Caribbean Islands. In these locations, the dengue fever
arbovirus is endemic, meaning that the virus naturally
and consistently lives in that location. The disease only
shows up in the United States sporadically.
In order to understand how dengue fever is transmitted, several terms need to be defined. The word
‘‘host’’ means an animal (including a human) that
can be infected with a particular disease. The word
‘‘vector’’ means an organism that can carry a particular disease-causing agent (like a virus or bacteria)
without actually developing the disease. The vector
can then pass the virus or bacteria on to a new host.
Many of the common illnesses in the United
States (including the common cold, many viral causes
of diarrhea, and influenza or ‘‘flu’’) are spread because
the viruses that cause these illness can be passed
directly from person to person. However, dengue
fever cannot be passed directly from one infected person to another. Instead, the virus responsible for dengue fever requires an intermediate vector, a mosquito,
that carries the virus from one host to another. The
mosquito that carries the arbovirus responsible for
dengue fever is the same type of mosquito that can
transmit other diseases, including yellow fever. This
mosquito is called Aedes egypti. The most common
victims are children younger than 10 years of age.

Causes and symptoms
Dengue fever can occur when a mosquito carrying
the arbovirus bites a human, passing the virus on to
the new host. Once in the body, the virus travels to
various glands where it multiplies. The virus can then
enter the bloodstream. The presence of the virus
within the blood vessels, especially those feeding the
skin, causes changes to these blood vessels. The vessels
swell and leak. The spleen and lymph nodes become
1132

enlarged, and patches of liver tissue die. A process
called disseminated intravascular coagulation (DIC)
occurs, where chemicals responsible for clotting are
used up and lead to a risk of severe bleeding
(hemorrhage).
After the virus has been transmitted to the human
host, a period of incubation occurs. During this time
(lasting about five to eight days) the virus multiplies.
Symptoms of the disease appear suddenly and include
high fever, chills, headache, eye pain, red eyes, enlarged
lymph nodes, a red flush to the face, lower back pain,
extreme weakness, and severe aches in the legs and joints.
This initial period of illness lasts about two or
three days. After this time, the fever drops rapidly
and the patient sweats heavily. After about a day of
feeling relatively well, the patient’s temperature
increases again, although not as much as the first
time. A rash of small red bumps begins on the arms
and legs, spreading to the chest, abdomen, and back.
It rarely affects the face. The palms of the hands and
the soles of the feet become swollen and turn bright
red. The characteristic combination of fever, rash, and
headache are called the ‘‘dengue triad.’’ Most people
recover fully from dengue fever, although weakness
and fatigue may last for several weeks. Once a person
has been infected with dengue fever, his or her immune
system keeps producing cells that prevent reinfection
for about a year.
More severe illness may occur in some people.
These people may be experiencing dengue fever for
the first time. However, in some cases a person may
have already had dengue fever at one time, recovered,
and then is reinfected with the virus. In these cases, the
first infection teaches the immune system to recognize
the presence of the arbovirus. When the immune cells
encounter the virus during later infections, the
immune system over-reacts. These types of illnesses,
called dengue hemorrhagic fever (DHF) or dengue
shock syndrome (DSS), involve more severe symptoms. Fever and headache are the first symptoms,
but the other initial symptoms of dengue fever are
absent. The patient develops a cough, followed by the
appearance of small purplish spots (petechiae) on the
skin. These petechiae are areas where blood is leaking
out of the vessels. Large bruised areas appear as the
bleeding worsens and abdominal pain may be severe.
The patient may begin to vomit a substance that looks
like coffee grounds. This is actually a sign of bleeding
into the stomach. As the blood vessels become more
damaged, they leak more and continue to increase in
diameter (dilate), causing a decrease in blood flow to
all tissues of the body. This state of low blood flow is
called shock. Shock can result in damage to the body’s
GALE ENCYCLOPEDIA OF MEDICINE

Endemic—Naturally and consistently present in a
certain geographical region.
Host—The organism (such as a monkey or human)
in which another organism (such as a virus or
bacteria) is living.
Vector—A carrier organism (such as a fly or
mosquito) that delivers a virus (or other agent of
infection) to a host.

organs (especially the heart and kidneys) because low
blood flow deprives them of oxygen.

Diagnosis
Diagnosis should be suspected in endemic areas
whenever a high fever goes on for two to seven days,
especially if accompanied by a bleeding tendency.
Symptoms of shock should suggest the progression
of the disease to DSS.
The arbovirus causing dengue fever is one of the
few types of arbovirus that can be isolated from the
serum of the blood. The serum is the fluid in which
blood cells are suspended. Serum can be tested because
the phase in which the virus travels throughout the
bloodstream is longer in dengue fever than in other
arboviral infections. A number of tests are used to
look for reactions between the patient’s serum and
laboratory-produced antibodies. Antibodies are special
cells that recognize the markers (or antigens) present on
invading organisms. During these tests, antibodies are
added to a sample of the patient’s serum. Healthcare
workers then look for reactions that would only occur if
viral antigens were present in that serum.

Treatment
There is no treatment available to shorten the
course of dengue fever, DHF, or DSS. Medications
can be given to lower the fever and to decrease the pain
of muscle aches and headaches. Fluids are given
through a needle in a vein to prevent dehydration.
Blood transfusions may be necessary if severe hemorrhaging occurs. Oxygen should be administered to
patients in shock.

Prognosis
The prognosis for uncomplicated dengue fever is
very good, and almost 100% of patients fully recover.
GALE ENCYCLOPEDIA OF MEDICINE

However, as many as 6–30% of all patients die when
DHF occurs. The death rate is especially high among
the youngest patients (under one year old). In places
where excellent medical care is available, very close
monitoring and immediate treatment of complications
lowers the death rate among DHF and DSS patients to
about 1%.

Prevention
Prevention of dengue fever means decreasing the
mosquito population. Any sources of standing water
(buckets, vases, etc.) where the mosquitoes can breed
must be eliminated. Mosquito repellant is recommended for those areas where dengue fever is endemic.
To help break the cycle of transmission, sick patients
should be placed in bed nets so that mosquitoes cannot
bite them and become arboviral vectors.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Dental caries see Tooth decay
Dental cavity see Tooth decay
Dental hygiene see Oral hygiene
Dental injuries see Dental trauma

I Dental trauma
Definition
Dental trauma is injury to the mouth, including
teeth, lips, gums, tongue, and jawbones. The most
common dental trauma is a broken or lost tooth.

Description
Dental trauma may be inflicted in a number of
ways: contact sports, motor vehicle accidents, fights,
falls, eating hard foods, drinking hot liquids, and
other such mishaps. As oral tissues are highly sensitive, injuries to the mouth are typically very painful.
Dental trauma should receive prompt treatment from
a dentist.
1133

Dental trauma

KEY TERMS

Dental trauma

Causes and symptoms
Soft tissue injuries, such as a ‘‘fat lip,’’ a burned
tongue, or a cut inside the cheek, are characterized by
pain, redness, and swelling with or without bleeding. A
broken tooth often has a sharp edge that may cut the
tongue and cheek. Depending on the position of the
fracture, the tooth may or may not cause toothache
pain. When a tooth is knocked out (evulsed), the socket
is swollen, painful, and bloody. A jawbone may be
broken if the upper and lower teeth no longer fit
together properly (malocclusion), or if the jaws have
pain with limited ability to open and close (mobility),
especially around the temporomandibular joint (TMJ).

Diagnosis
Dental trauma is readily apparent upon examination. Dental x rays may be taken to determine the
extent of the damage to broken teeth. More comprehensive x rays are needed to diagnose a broken jaw.

Treatment
Soft tissue injuries may require only cold compresses
to reduce swelling. Bleeding may be controlled with
direct pressure applied with clean gauze. Deep lacerations and punctures may require stitches. Pain may be
managed with aspirin or acetaminophen (Tylenol,
Aspirin Free Excedrin) or ibuprofen (Motrin, Advil).
Treatment of a broken tooth will vary depending
on the severity of the fracture. For immediate first aid,
the injured tooth and surrounding area should be
rinsed gently with warm water to remove dirt, then
covered with a cold compress to reduce swelling and
ease pain. A dentist should examine the injury as soon
as possible. Any pieces from the broken tooth should
be saved and brought along.
If a piece of the outer tooth has chipped off, but
the inner core (pulp) is undisturbed, the dentist may
simply smooth the rough edges or replace the missing
section with a small composite filling. In some cases, a
fragment of broken tooth may be bonded back into
place. If enough tooth is missing to compromise the
entire tooth structure, but the pulp is not permanently
damaged, the tooth will require a protective coverage
with a gold or porcelain crown. If the pulp has been
seriously damaged, the tooth will require root canal
treatment before it receives a crown. A tooth, that is
vertically fractured or fractured below the gumline will
require root canal treatment and protective restoration. A tooth that no longer has enough remaining
structure to retain a crown may have to be extracted
(surgically removed).
1134

When a permanent tooth has been knocked out, it
may be saved with prompt action. The tooth must be
found immediately after it has been lost. It should be
picked up by the natural crown (the top part covered by
hard enamel). It must not be handled by the root. If the
tooth is dirty, it may be gently rinsed under running
water. It should never be scrubbed, and it should never
be washed with soap, toothpaste, mouthwash, or other
chemicals. The tooth should not be dried or wrapped in
a tissue or cloth. It must be kept moist at all times.
The tooth may be placed in a clean container of
milk, cool water with or without a pinch of salt, or in
saliva. If possible, the patient and the tooth should be
brought to the dentist within 30 minutes of the tooth
loss. Rapid action improves the chances of successful
re-implantation; however, it is possible to save a tooth
after 30 minutes, if the tooth has been kept moist and
handled properly.
The body usually rejects re-implantation of a primary (baby) tooth. In this case, the empty socket is
treated as a soft tissue injury and monitored until the
permanent tooth erupts.
A broken jaw must be set back into its proper
position and stabilized with wires while it heals.
Healing may take six weeks or longer, depending on
the patient’s age and the severity of the fracture.

Alternative treatment
There is no substitute for treatment by a dentist or
other medical professional. There are, however,
homeopathic remedies and herbs that can be used
simultaneously with dental care and throughout the
healing process. Homeopathic arnica (Arnica montana) should be taken as soon as possible after the
injury to help the body deal with the trauma.
Repeating a dose several times daily for the duration
of healing is also useful. Homeopathic hypericum
(Hypericum perforatum) can be taken if nerve pain is
involved, especially with a tooth extraction or root
canal. Homeopathic comfrey (officinale) Symphytum
may be helpful in treating pain due to broken jaw
bones, but should only be used after the bones have
been reset. Calendula (Calendula officinalis) and plantain (Plantago major) can be used as a mouth rinse to
enhance tissue healing. These herbs should not be
used with deep lacerations that need to heal from the
inside first.

Prognosis
When dental trauma receives timely attention and
proper treatment, the prognosis for healing is good. As
GALE ENCYCLOPEDIA OF MEDICINE

Crown—The natural part of the tooth covered by
enamel. A restorative crown is a protective shell
that fits over a tooth.
Eruption—The process of a tooth breaking through
the gum tissue to grow into place in the mouth.
Evulsion—The forceful, and usually accidental,
removal of a tooth from its socket in the bone.
Extraction—The surgical removal of a tooth from
its socket in the bone.
Malocclusion—A problem in the way the upper
and lower teeth fit together in biting or chewing.
Pulp—The soft innermost layer of a tooth containing blood vessels and nerves.

equipment has the likelihood of dental trauma that
may be prevented or substantially reduced in severity
with the use of mouthguards.
Resources
ORGANIZATIONS

American Academy of Pediatric Dentistry. 211 East
Chicago Ave., Ste. 700, Chicago, IL 60611-2616. (312)
337-2169. <http://www.aapd.org>.
American Association of Endodontists. 211 East Chicago
Ave., Ste. 1100, Chicago, IL 60611-2691. (800)
872-3636. <http://www.aae.org>.
American Association of Oral and Maxillofacial Surgeons.
9700 West Bryn Mawr Ave., Rosemont, IL 60018-5701.
(847) 678-6200. <http://www.aaoms.org>.
American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.

Root canal treatment—The process of removing
diseased or damaged pulp from a tooth, then filling
and sealing the pulp chamber and root canals.
Temporomandibular joint (TMJ)—The jaw joint
formed by the mandible (lower jaw bone) moving
against the temporal (temple and side) bone of
the skull.

with other types of trauma, infection may be a complication, but a course of antibiotics is generally effective.

Prevention
Most dental trauma is preventable. Car seat belts
should always be worn, and young children should be
secured in appropriate car seats. Homes should be
monitored for potential tripping and slipping hazards.
Child-proofing measures should be taken, especially
for toddlers. In addition to placing gates across stairs
and padding sharp table edges, electrical cords should
be tucked away. Young children may receive severe
oral burns from gnawing on live power cords.
Everyone who participates in contact sports
should wear a mouthguard to avoid dental trauma.
Athletes in football, ice hockey, wrestling, and boxing
commonly wear mouthguards. The mandatory use of
mouthguards in football prevents about 200,000 oral
injuries annually. Mouthguards should also be worn
along with helmets in noncontact sports such as skateboarding, in-line skating, and bicycling. An athlete
who does not wear a mouthguard is 60 times more
likely to sustain dental trauma than one who does.
Any activity involving speed, an increased chance of
falling, and potential contact with a hard piece of
GALE ENCYCLOPEDIA OF MEDICINE

Bethany Thivierge

Depersonalization disorder see Dissociative
disorders

I Depo-Provera/Norplant
Definition
Norplant is a long-acting hormone that is inserted
under the skin and prevents conception for up to five
years. Depo-Provera is also a hormone, but is administered by intramuscular injection and provides protection against pregnancy for three months. Lunelle is
another injectable contraceptive that is administered
monthly (every 28 to 30 days); it was approved by the
Food and Drug Administration (FDA) in October
2000. The hormone in Norplant and Depo-Provera is
progestin, a synthetic hormone similar to one found
naturally in a woman’s body; Lunelle contains the
hormones progestin and estrogen.

Purpose
The purpose of these hormones is to prevent pregnancy; they are about 99% effective in achieving this
goal. No hormonal contraceptive methods provide
protection from AIDS or other sexually transmitted
diseases.
Depo-Provera and Lunelle are given as an injection and work in several ways to prevent conception.
First, the egg (ovum) is prevented from maturing and
being released. The mucus in the cervix (opening into
1135

Depo-Provera/Norplant

KEY TERMS

Depo-Provera/Norplant

the uterus or womb) becomes thicker, making it difficult for the sperm to enter. Depo-Provera and Lunelle
also cause the lining of the uterus to become thinner,
making implantation of a fertilized egg unlikely.
An injection of Depo-Provera or Lunelle must be
given within the first five days of a normal period.
Depo-Provera provides protection against pregnancy
for three months, while Lunelle provides similar protection for one month. Ovulation (release of a mature
egg) typically occurs within 60 days of the last injection of Lunelle, about twice as fast after use of DepoProvera. Also, because Lunelle is a combined
hormone contraceptive as opposed to progestin-only
Depo-Provera and Norplant, it is less likely to cause
irregular or absent menstruation.
Norplant capsules contain a synthetic hormone
that is slowly released over a period of up to five
years. It functions like Depo-Provera in that it prevents the ovaries from producing ova (eggs) and also
results in thicker mucus in the cervix, which prevents
the sperm from passing through the cervix. Norplant
can be inserted at any time.

Preparation
The woman being considered for Depo-Provera
or Lunelle will have a pelvic and breast examination, a
Pap test (a microscopic examination of cell samples
taken from the cervix), blood pressure check, weight
check, and a review of her medical history. Women
who have diabetes mellitus, major depression, blood
clotting problems, liver disease, or weight problems
should use these methods only under strict medical
supervision. Depo-Provera or Lunelle should not be
used if the woman is pregnant, has unexplained vaginal bleeding, suffers from severe liver disease, has
breast cancer, or has a history of blood clots or stroke.
Individuals who select Norplant will receive the
same basic physical examination. If approved for this
method, a site of implantation will be selected (usually
the inside of the upper arm), and the area prepared for
minor surgery. The skin will be washed with soap and
water, and an antiseptic, such as iodine solution, will
be applied. The physician will use a local anesthetic to
numb the area, a small incision will be made, the six
Norplant capsules will be inserted, and the incision
sewn up (sutured). Protection against pregnancy normally begins within 24 hours. If necessary, the
implants can be removed in 15–20 minutes. Norplant
should not be used by women who are pregnant, have
blood clotting problems, or have unexplained vaginal
bleeding. Advantages include light periods with less
cramping and decreased anemia. This form of birth
1136

A physician inserts a contraceptive implant under the skin
of a woman’s arm. (Photo Researchers, Inc. Reproduced by
permission.)

KEY TERMS
Hormone—A chemical produced in a gland or
organ and transported by the blood to another
area of the body where it produces a specific effect.
Pap test—A microscopic examination of cell
samples taken from the cervix.

control may also be protective against endometrial
cancer.
Because Depo-Provera and Norplant use only the
hormone progestin, they may provide an alternative
for women who can not use estrogen-containing birth
control pills. One benefit of Lunelle, however, is that
its effects wear off more quickly than Depo-Provera,
an important factor in the event that a woman has
serious side effects or wants to become pregnant.

Risks
The most common side effects associated with
Depo-Provera and Lunelle are yellowing of the skin,
headache, nervousness, dizziness, abdominal pain, hair
loss, rash, increase in the number of migraine headaches, increased or decreased interest in sexual intercourse, the development of dark spots on the skin,
depression, and weakness. Danger signs that need to
reported immediately include weight gain, heavy vaginal bleeding, frequent urination, blurred vision, fainting, severe abdominal pain, and coughing up blood.
Because the effects of Depo-Provera may last up to
12 weeks, it may take a longer time for women trying
GALE ENCYCLOPEDIA OF MEDICINE

The main reactions to Norplant include headache,
weight gain, irregular periods or no period at all,
breast tenderness, acne, gain or loss of facial hair,
color changes of the skin over the area of insertion,
and ovarian cysts. The doctor should be notified
immediately of lumps in the breast, heavy vaginal
bleeding, yellowing of the skin or eyes, or infection
of the incision. Women who use Norplant are discouraged from smoking.

Normal results
These hormone contraceptive methods normally
result in a success rate of 99%.
Resources
OTHER

‘‘Depo Provera.’’ Planned Parenthood of Western
Washington. <http://www.ppww.org/depo.htm>.
‘‘Is Depo-Provera For You?’’ Planned Parenthood
Federation of America, Inc. <http://www.plannedparenthood.org/Library/birthcontrol/depoforyou.html>.
‘‘Lunelle.’’ Food and Drug Administration (FDA)Page.
<http://www.fda.gov/cder/foi/label/2000/
20874lbl.pdf>.

Donald G. Barstow, RN

Depression see Bipolar disorder; Postpartum
depression

I Depressive disorders
Definition
Depression or depressive disorders (unipolar
depression) are mental illnesses characterized by a
profound and persistent feeling of sadness or despair
and/or a loss of interest in things that once were pleasurable. Disturbance in sleep, appetite, and mental
processes are a common accompaniment.

Description
Everyone experiences feelings of unhappiness and
sadness occasionally. But when these depressed feelings start to dominate everyday life and cause physical
and mental deterioration, they become what are
known as depressive disorders. Each year in the
GALE ENCYCLOPEDIA OF MEDICINE

United States, depressive disorders affect an estimated
17 million people at an approximate annual direct and
indirect cost of $53 billion. One in four women is likely
to experience an episode of severe depression in her
lifetime, with a 10–20% lifetime prevalence, compared
to 5–10% for men. The average age a first depressive
episode occurs is in the mid-20s, although the disorder
strikes all age groups indiscriminately, from children
to the elderly.
There are two main categories of depressive disorders: major depressive disorder and dysthymic disorder. Major depressive disorder is a moderate to
severe episode of depression lasting two or more
weeks. Individuals experiencing this major depressive
episode may have trouble sleeping, lose interest in
activities they once took pleasure in, experience a
change in weight, have difficulty concentrating, feel
worthless and hopeless, or have a preoccupation with
death or suicide. In children, the major depression may
appear as irritability.
While major depressive episodes may be acute
(intense but short-lived), dysthymic disorder is an
ongoing, chronic depression that lasts two or more
years (one or more years in children) and has an
average duration of 16 years. The mild to moderate
depression of dysthymic disorder may rise and fall in
intensity, and those afflicted with the disorder may
experience some periods of normal, non-depressed
mood of up to two months in length. Its onset is
gradual, and dysthymic patients may not be able to
pinpoint exactly when they started feeling depressed.
Individuals with dysthymic disorder may experience a
change in sleeping and eating patterns, low selfesteem, fatigue, trouble concentrating, and feelings of
hopelessness.
Depression also can occur in bipolar disorder, an
affective mental illness that causes radical emotional
changes and mood swings, from manic highs to
depressive lows. The majority of bipolar individuals
experience alternating episodes of mania and
depression.

Causes and symptoms
The causes behind depression are complex and
not yet fully understood. While an imbalance of certain neurotransmitters—the chemicals in the brain
that transmit messages between nerve cells—is
believed to be key to depression, external factors
such as upbringing (more so in dysthymia than
major depression) may be as important. For example,
it is speculated that, if an individual is abused and
neglected throughout childhood and adolescence, a
1137

Depressive disorders

to conceive to become pregnant after discontinuing
the injections.

Depressive disorders



Diminished ability to think or to concentrate, or
indecisiveness.



Recurrent thoughts of death or suicide and/or
suicide attempts.

Signs of Depression

Lack of interest or pleasure in daily activities
Significant weight loss (without dieting) or weight gain
Difficulty sleeping or excessive sleeping
Loss of energy
Feelings of worthlessness or guilt
Difficulty in making decisions
Restlessness
Recurrent thoughts of death

pattern of low self-esteem and negative thinking may
emerge. From that, a lifelong pattern of depression
may follow. A 2003 study reported that two-thirds of
patients with major depression say they also suffer
from chronic pain. A 2004 study linked severe obesity
with major depression. Another study showed a
strong relationship between smoking and depression
among teens.
Heredity seems to play a role in who develops
depressive disorders. Individuals with major depression in their immediate family are up to three times
more likely to have the disorder themselves. It would
seem that biological and genetic factors may make
certain individuals pre-disposed or prone to depressive
disorders, but environmental circumstances often may
trigger the disorder.
External stressors and significant life changes,
such as chronic medical problems, death of a loved
one, divorce or estrangement, miscarriage, or loss of a
job, also can result in a form of depression known as
adjustment disorder. Although periods of adjustment
disorder usually resolve themselves, occasionally they
may evolve into a major depressive disorder.
Major depressive episode
Individuals experiencing a major depressive episode have a depressed mood and/or a diminished
interest or pleasure in activities. Children experiencing
a major depressive episode may appear or feel irritable
rather than depressed. In addition, five or more of the
following symptoms will occur on an almost daily
basis for a period of at least two weeks:


Significant change in weight.



Insomnia or hypersomnia (excessive sleep).



Psychomotor agitation or retardation.



Fatigue or loss of energy.



Feelings of worthlessness or inappropriate guilt.

1138

Dysthymic disorder
Dysthymia commonly occurs in tandem with
other psychiatric and physical conditions. Up to
70% of dysthymic patients have both dysthymic disorder and major depressive disorder, known as double
depression. Substance abuse, panic disorders, personality disorders, social phobias, and other psychiatric
conditions also are found in many dysthymic patients.
Dysthymia is prevalent in patients with certain
medical conditions, including multiple sclerosis,
AIDS, hypothyroidism, chronic fatigue syndrome,
Parkinson’s disease, diabetes, and post-cardiac transplantation. The connection between dysthymic disorder and these medical conditions is unclear, but it may
be related to the way the medical condition and/or its
pharmacological treatment affects neurotransmitters.
Dysthymic disorder can lengthen or complicate the
recovery of patients also suffering from medical
conditions.
Along with an underlying feeling of depression,
people with dysthymic disorder experience two or
more of the following symptoms on an almost daily
basis for a period for two or more years (most
suffer for five years), or one year or more for
children:


under or overeating



insomnia or hypersomnia



low energy or fatigue



low self-esteem



poor concentration or trouble making decisions



feelings of hopelessness

Diagnosis
In addition to an interview, several clinical
inventories or scales may be used to assess a patient’s
mental status and determine the presence of depressive symptoms. Among these tests are: the Hamilton
Depression Scale (HAM-D), Child Depression
Inventory (CDI), Geriatric Depression Scale
(GDS), Beck Depression Inventory (BDI), and the
Zung Self-Rating Scale for Depression. These tests
may be administered in an outpatient or hospital
setting by a general practitioner, social worker,
psychiatrist, or psychologist.
GALE ENCYCLOPEDIA OF MEDICINE

Depressive disorders

Subgenual
prefrontal
cortex

Subgenual
prefrontal
cortex

Normal

Abnormal

Recent scientific research has indicated that the size of the subgenual prefrontal cortex of the brain (located behind the bridge of
the nose) may be a determining factor in hereditary depressive disorders. (Illustration by Electronic Illustrators Group.)

Treatment
Major depressive and dysthymic disorders are
typically treated with antidepressants or psychosocial
therapy. Psychosocial therapy focuses on the personal
and interpersonal issues behind depression, while antidepressant medication is prescribed to provide more
immediate relief for the symptoms of the disorder.
When used together correctly, therapy and antidepressants are a powerful treatment plan for the depressed
patient.
Antidepressants
Selective serotonin reuptake inhibitors (SSRIs)
such as fluoxetine (Prozac) and sertraline (Zoloft)
reduce depression by increasing levels of serotonin, a
neurotransmitter. Some clinicians prefer SSRIs for
treatment of dysthymic disorder. Anxiety, diarrhea,
drowsiness, headache, sweating, nausea, poor sexual
functioning, and insomnia all are possible side effects
of SSRIs. In early 2004, a joint panel of the U.S. Food
and Drug Administration (FDA) issued stronger
warnings to physicians and parents about increased
risk of suicide among children and adolescents taking
SSRIs.
Tricyclic antidepressants (TCAs) are less expensive than SSRIs, but have more severe side-effects,
which may include persistent dry mouth, sedation,
GALE ENCYCLOPEDIA OF MEDICINE

dizziness, and cardiac arrhythmias. Because of these
side effects, caution is taken when prescribing TCAs to
elderly patients. TCAs include amitriptyline (Elavil),
imipramine (Tofranil), and nortriptyline (Aventyl,
Pamelor). A 10-day supply of TCAs can be lethal if
ingested all at once, so these drugs may not be a
preferred treatment option for patients at risk for
suicide.
Monoamine oxidase inhibitors (MAOIs) such as
tranylcypromine (Parnate) and phenelzine (Nardil)
block the action of monoamine oxidase (MAO), an
enzyme in the central nervous system. Patients taking
MAOIs must cut foods high in tyramine (found in
aged cheeses and meats) out of their diet to avoid
potentially serious hypertensive side effects.
Heterocyclics include bupropion (Wellbutrin) and
trazodone (Desyrel). Bupropion should not be prescribed to patients with a seizure disorder. Side effects
of the drug may include agitation, anxiety, confusion,
tremor, dry mouth, fast or irregular heartbeat, headache, low blood pressure, and insomnia. Because trazodone has a sedative effect, it is useful in treating
depressed patients with insomnia. Other possible side
effects of trazodone include dry mouth, gastrointestinal distress, dizziness, and headache. In 2003,
Wellbutrin’s manufacturer released a once–daily version of the drug that offered low risk of sexual side
effects or weight gain.
1139

Depressive disorders

Electroconvulsant therapy
ECT, or electroconvulsive therapy, usually is
employed after all therapy and pharmaceutical treatment options have been explored. However, it is sometimes used early in treatment when severe depression is
present and the patient refuses oral medication, or
when the patient is becoming dehydrated, extremely
suicidal, or psychotic.
The treatment consists of a series of electrical
pulses that move into the brain through electrodes on
the patient’s head. ECT is given under general anesthesia and patients are administered a muscle relaxant to
prevent convulsions. Although the exact mechanisms
behind the success of ECT therapy are not known, it is
believed that the electrical current modifies the electrochemical processes of the brain, consequently
relieving depression. Headaches, muscle soreness,
nausea, and confusion are possible side effects immediately following an ECT procedure. Memory loss,
typically transient, also has been reported in ECT
patients.

Alternative treatment

Positron emission tomography (PET) scans comparing a
normal brain with that of someone with a depressed mental
disorder. (Photo Researchers, Inc. Reproduced by permission.)

Psychosocial therapy
Psychotherapy explores an individual’s life to
bring to light possible contributing causes of the present depression. During treatment, the therapist helps
the patient to become self-aware of his or her thinking
patterns and how they came to be. There are several
different subtypes of psychotherapy, but all have the
common goal of helping the patient develop healthy
problem solving and coping skills.
Cognitive-behavioral therapy assumes that the
patient’s faulty thinking is causing the current
depression and focuses on changing the depressed
patient’s thought patterns and perceptions. The
therapist helps the patient identify negative or distorted thought patterns and the emotions and
behavior that accompany them, and then retrains
the depressed individual to recognize the thinking
and react differently to it.
1140

St. John’s wort (Hypericum perforatum) is used
throughout Europe to treat depressive symptoms.
Unlike traditional prescription antidepressants, this
herbal antidepressant has few reported side effects.
Despite uncertainty concerning its effectiveness, a
2003 report said acceptance of the treatment continues
to increase. A poll showed that about 41% of 15,000
science professionals in 62 countries said they would
use St. John’s wort for mild to moderate depression.
Although St. John’s wort appears to be a safe alternative to conventional antidepressants, care should be
taken, as the herb can interfere with the actions of
some pharmaceuticals. The usual dose is 300 mg
three times daily.
Homeopathic treatment also can be therapeutic in
treating depression. Good nutrition, proper sleep,
exercise, and full engagement in life are very important
to a healthy mental state.
In several small studies, S-adenosyl-methionine
(SAM, SAMe) was shown to be more effective than
placebo and equally effective as tricyclic antidepressants in treating depression. The usual dosage is 200
mg to 400 mg twice daily. In 2003, a U.S. Department
of Health and Human Services team reviewed 100
clinical trials on SAMe and concluded that it worked
as well as many prescription medications without the
side effects of stomach upset and decreased sexual
desire.
GALE ENCYCLOPEDIA OF MEDICINE

Hypersomnia—The need to sleep excessively; a
symptom of dysthymic and major depressive
disorder.
Neurotransmitter—A chemical in the brain that
transmits messages between neurons, or nerve
cells. Changes in the levels of certain neurotransmitters, such as serotonin, norepinephrine, and
dopamine, are thought to be related to depressive
disorders.
Psychomotor agitation—Disturbed physical and
mental processes (e.g., fidgeting, wringing of
hands, racing thoughts); a symptom of major
depressive disorder.
Psychomotor retardation—Slowed physical and
mental processes (e.g., slowed thinking, walking,
and talking); a symptom of major depressive
disorder.

In 2003, a report from Great Britain emphasized
that more physicians should encourage alternative
treatments such as behavioral and self-help programs,
supervised exercise programs, and watchful waiting
before subscribing antidepressant medications for
mild depression.

Prognosis
Untreated or improperly treated depression is the
number one cause of suicide in the United States.
Proper treatment relieves symptoms in 80–90% of
depressed patients. After each major depressive episode, the risk of recurrence climbs significantly—50%
after one episode, 70% after two episodes, and 90%
after three episodes. For this reason, patients need to
be aware of the symptoms of recurring depression and
may require long-term maintenance treatment of antidepressants and/or therapy.
Research has found that depression may lead to
other problems as well. Increased risk of heart disease
has been linked to depression, particularly in postmenopausal women. And while chronic pain may
cause depression, a 2004 study in Canada revealed
that depression also may lead to back pain.

Prevention
Patient education in the form of therapy or selfhelp groups is crucial for training patients with
GALE ENCYCLOPEDIA OF MEDICINE

depressive disorders to recognize symptoms of depression and to take an active part in their treatment
program. Extended maintenance treatment with antidepressants may be required in some patients to prevent relapse. Early intervention for children with
depression is effective in arresting development of
more severe problems.
Resources
PERIODICALS

‘‘Depression Can Lead to Back Pain.’’ Biotech Week, March
24, 2004: 576.
‘‘Depression May Be a Risk Factor for Heart Disease, Death
in Older Women.’’ Women’s Health Weekly, March 4,
2004: 90.
‘‘FDA Approves Once-daily Supplement.’’ Biotech Week,
September 24, 2003: 6.
‘‘FDA Panel Urges Stronger Warnings of Child Suicide.’’
SCRIP World Pharmaceutical News, February 6, 2004: 24.
Jancin, Bruce. ‘‘Chronic Pain Affects 67% of Patients With
Depression: ‘Stunning’ Finding in Primary Care
Study.’’ Internal Medicine News, September 15, 2003: 4.
‘‘National Study Indicates Obesity Is Linked to Major
Depression.’’ Drug Week, February 13, 2004: 338.
‘‘A Natural Mood-booster that Really Works: a Group of
Noted Researchers Found that the Supplement SAMe
Works as Well as Antidepressant Drugs.’’ Natural
Health, July 2003: 22.
‘‘Researchers See Link Between Depression, Smoking.’’
Mental Health Weekly, March 1, 2004: 8.
‘‘St. John’s Wort Healing Reputation Upheld.’’
Nutraceuticals International, September 2003.
‘‘Try Alternatives Before Using Antidepressants.’’ GP,
September 29, 2003: 12.
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<http://www.apa.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.
National Depressive and Manic-Depressive Association
(NDMDA). 730 N. Franklin St., Suite 501, Chicago, IL
60610. (800) 826-3632. <http://www.ndmda.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Paula Anne Ford-Martin
Teresa G. Odle

Dermabrasion see Skin resurfacing
1141

Depressive disorders

KEY TERMS

Dermatitis

I Dermatitis
Definition
Dermatitis is a general term used to describe
inflammation of the skin.

Description
Most types of dermatitis are characterized by an
itchy pink or red rash.
Contact dermatitis is an allergic reaction to something that irritates the skin and is manifested by one or
more lines of red, swollen, blistered skin that may itch
or seep. It usually appears within 48 hours after touching or brushing against a substance to which the skin is
sensitive. The condition is more common in adults
than in children.
Contact dermatitis can occur on any part of the
body, but it usually affects the hands, feet, and groin.
Contact dermatitis usually does not spread from one
person to another, nor does it spread beyond the area
exposed to the irritant unless affected skin comes into
contact with another part of the body. However, in the
case of some irritants, such as poison ivy, contact
dermatitis can be passed to another person or to
another part of the body.
Stasis dermatitis is characterized by scaly, greasy
looking skin on the lower legs and around the ankles.
Stasis dermatitis is most apt to affect the inner side of
the calf.
Nummular dermatitis, which is also called nummular eczematous dermatitis or nummular eczema, generally affects the hands, arms, legs, and buttocks of men
and women older than 55 years of age. This stubborn
inflamed rash forms circular, sometimes itchy, patches
and is characterized by flares and periods of inactivity.
Atopic dermatitis is characterized by itching, scaling, swelling, and sometimes blistering. In early childhood it is called infantile eczema and is characterized
by redness, oozing, and crusting. It is usually found on
the face, inside the elbows, and behind the knees.
Seborrheic dermatitis may be dry or moist and is
characterized by greasy scales and yellowish crusts on
the scalp, eyelids, face, external surfaces of the ears,
underarms, breasts, and groin. In infants it is called
‘‘cradle cap.’’

Causes and symptoms
Allergic reactions are genetically determined, and
different substances cause contact dermatitis to
1142

develop in different people. A reaction to resin produced by poison ivy, poison oak, or poison sumac is
the most common source of symptoms. It is, in fact,
the most common allergy in this country, affecting one
of every two people in the United States.
Flowers, herbs, and vegetables can also affect the
skin of some people. Burns and sunburn increase the
risk of dermatitis developing, and chemical irritants
that can cause the condition include:


chlorine



cleansers



detergents and soaps



fabric softeners



glues used on artificial nails



perfumes



topical medications

Contact dermatitis can develop when the first
contact occurs or after years of use or exposure.
Stasis dermatitis, a consequence of poor circulation, occurs when leg veins can no longer return blood
to the heart as efficiently as they once did. When that
happens, fluid collects in the lower legs and causes
them to swell. Stasis dermatitis can also result in a
rash that can break down into sores known as stasis
ulcers.
The cause of nummular dermatitis is not known,
but it usually occurs in cold weather and is most
common in people who have dry skin. Hot weather
and stress can aggravate this condition, as can the
following:


allergies



fabric softeners



soaps and detergents



wool clothing



bathing more than once a day

Atopic dermatitis can be caused by allergies,
asthma, or stress, and there seems to be a genetic
predisposition for atopic conditions. It is sometimes
caused by an allergy to nickel in jewelry.
Seborrheic dermatitis (for which there may also
be a genetic predisposition) is usually caused by
overproduction of the oil glands. In adults it can
be associated with diabetes mellitus or gold allergy.
In infants and adults it may be caused by a biotin
deficiency.
GALE ENCYCLOPEDIA OF MEDICINE

Dermatitis

Diagnosis
The diagnosis of dermatitis is made on the basis of
how the rash looks and its location. The doctor may
scrape off a small piece of affected skin for microscopic examination or direct the patient to discontinue
use of any potential irritant that has recently come into
contact with the affected area. Two weeks after the
rash disappears, the patient may resume use of the
substances, one at a time, until the condition recurs.
Eliminating the substance most recently added should
eliminate the irritation.
If the origin of the irritation has still not been
identified, a dermatologist may perform one or more
patch tests. This involves dabbing a small amount of a
suspected irritant onto skin on the patient’s back. If no
irritation develops within a few days, another patch
test is performed. The process continues until the
patient experiences an allergic reaction at the spot
where the irritant was applied.

Treatment
Treating contact dermatitis begins with eliminating
or avoiding the source of irritation. Prescription or overthe-counter corticosteroid creams can lessen inflammation and relieve irritation. Creams, lotions, or ointments
not specifically formulated for dermatitis can intensify
the irritation. Oral antihistamines are sometimes recommended to alleviate itching, and antibiotics are prescribed if the rash becomes infected. Medications taken
by mouth to relieve symptoms of dermatitis can make
skin red and scaly and cause hair loss.
Patients who have a history of dermatitis should
remove their rings before washing their hands. They
should use bath oils or glycerine-based soaps and
bathe in lukewarm saltwater.
Patting rather than rubbing the skin after bathing
and thoroughly massaging lubricating lotion or nonprescription cortisone creams into still-damp skin can
soothe red, irritated nummular dermatitis. Highly
concentrated cortisone preparations should not be
applied to the face, armpits, groin, or rectal area.
Periodic medical monitoring is necessary to detect
side effects in patients who use such preparations on
rashes covering large areas of the body.
Coal-tar salves can help relieve symptoms of
nummular dermatitis that have not responded to
other treatments, but these ointments have an unpleasant odor and stain clothing.
Patients who have stasis dermatitis should elevate
their legs as often as possible and sleep with a pillow
between the lower legs.
GALE ENCYCLOPEDIA OF MEDICINE

Dermatitis on hands and fingers. (Custom Medical Stock Photo.
Reproduced by permission.)

Tar or zinc paste may also be used to treat stasis
dermatitis. Because these compounds must remain in
contact with the rash for as long as two weeks, the
paste and bandages must be applied by a nurse or a
doctor.
Coal-tar shampoos may be used for seborrheic
dermatitis that occurs on the scalp. Sun exposure
after the use of these shampoos should be avoided
because the risk of sunburn of the scalp is increased.

Alternative treatment
Some herbal therapies can be useful for skin conditions. Among the herbs most often recommended
are:


Burdock root (Arctium lappa)



Calendula (Calendula officinalis) ointment



Chamomile (Matricaria recutita) ointment



Cleavers (Galium ssp.)



Evening primrose oil (Oenothera biennis)



Nettles (Urtica dioica)

Contact dermatitis can be treated botanically and
homeopathically. Grindelia (Grindelia spp.) and sassafras (Sassafras albidum) can help when applied topically. Determining the source of the problem and
eliminating it is essential. Oatmeal baths are very helpful in relieving the itch. Bentonite clay packs or any
mud pack draws the fluid out and helps dry up the
lesions. Cortisone creams are not recommended.
Stasis dermatitis should be treated by a trained
practitioner. This condition responds well to topical
herbal therapies, however, the cause must also be
addressed. Selenium-based shampoos, topical applications of flax oil and/or olive oil, and biotin
1143

Dermatomyositis

KEY TERMS

Injury to the lower leg can cause stasis dermatitis
to ulcerate (form open sores). If stasis ulcers develop, a
doctor should be notified immediately.

Allergic reaction—An inappropriate or exaggerated genetically determined reaction to a chemical
that occurs only on the second or subsequent exposures to the offending agent, after the first contact
has sensitized the body.

Yoga and other relaxation techniques may help
prevent atopic dermatitis caused by stress.

Corticosteriod—A group of synthetic hormones
that are used to prevent or reduce inflammation.
Toxic effects may result from rapid withdrawal after
prolonged use or from continued use of large doses.
Patch test—A skin test that is done to identify allergens. A suspected substance is applied to the skin.
After 24–48 hours, if the area is red and swollen, the
test is positive for that substance. If no reaction
occurs, another substance is applied. This is continued until the patient experiences an allergic
reaction where the irritant was applied to the skin.

A patient who has dermatitis should also notify a
doctor if any of the following occurs:

Rash—A spotted, pink or red skin eruption that may
be accompanied by itching and is caused by disease, contact with an allergen, food ingestion, or
drug reaction.
Ulcer—An open sore on the skin, resulting from
tissue destruction, that is usually accompanied by
redness, pain, or infection.

OTHER

supplementation are among the therapies recommended for seborrheic dermatitis.

Avoidance of sweating may aid in preventing
seborrheic dermatitis.



fever develops



skin oozes or other signs of infection appear



symptoms do not begin to subside after seven days’
treatment



he/she comes into contact with someone who has a
wart, cold sore, or other viral skin infection

Resources
‘‘Allergic Contact Dermatitis.’’ The Skin Site. April 10,
1998 (January 11, 2006). <http://www.skinsite.com/
info_allergic.htm>.

Maureen Haggerty

I Dermatomyositis
Definition

Prognosis
Dermatitis is often chronic, but symptoms can
generally be controlled.

Prevention
Contact dermatitis can be prevented by avoiding
the source of irritation. If the irritant cannot be
avoided completely, the patient should wear gloves
and other protective clothing whenever exposure is
likely to occur.
Immediately washing the exposed area with soap
and water can stem allergic reactions to poison ivy,
poison oak, or poison sumac, but because soaps can
dry the skin, patients susceptible to dermatitis should
use them only on the face, feet, genitals, and
underarms.
Clothing should be loose fitting and 100% cotton.
New clothing should be washed in dye-free, unscented
detergent before being worn.
1144

Dermatomyositis (DM) is a rare inflammatory
muscle disease that leads to destruction of muscle
tissue usually accompanied by pain and weakness.

Description
Dermatomyositis is one of a group of three related
diseases called inflammatory myopathies. The other
two are polymyositis and inclusion-body myositis.
These diseases are rare; only about 20,000 people in
the United States have dermatomyositis. Another estimates suggest that DM occurs in about 5.5 individuals
out of every one million. The disease is of unknown
origin and can develop in children and adults. Most
often individuals either develop DM either between
the ages of five and 14 or they do not develop it until
they are over age 45. In all age groups, females are
twice as likely to develop the disease than males.
Although DM causes pain and weakness, it is not
necessarily life threatening. However, adults, but not
children, who develop DM have an increased risk of
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The exact cause of dermatomyositis is unknown.
It is an autoimmune disease. In a healthy body, cells of
immune system attack only foreign or defective cells in
the body to protect it from disease. In an autoimmune
disease, the immune system attacks normal body cells.
In the case of DM, immune system cells attack healthy
cells of small blood vessels in the muscle and skin.
Over time, this causes muscle fiber to shrink and sometimes cuts off blood supply to the muscle. DM tends to
develop in muscles closest to the center of the body.
As yet, there is no clear explanation of what
causes an individual to develop DM. It is thought
that the disease may be triggered by a virus or exposure to certain drugs or vaccines. According to the
Muscular Dystrophy Association, recent research suggests developing DM may be related to the mixing of
blood cells that sometimes occurs between the mother
and fetus during pregnancy. The disease is not directly
inherited, although there may be some genetic sensitivity toward whatever triggers it.
Often the first sign of DM is the development of a
patchy, scaly, violet to dark red skin rash on the face,
neck, shoulders, upper chest, knees, or back. Often the
rash appears before any signs of illness or muscle
weakness. About 40% of children and teens develop
hard, painful bumps under the skin that are deposits of
calcium, a mineral used in bone formation. This condition, called calcinosis, is much less common in
adults.
Muscle weakness, especially in the upper arms,
hips, thighs, and neck, becomes apparent in activities
such as climbing stairs or reaching up over the head.
This weakness develops after the rash appears. Some
people have difficulty swallowing and chewing when
the muscles of the face and esophagus are affected.
Individuals may also feel tried, weak, have a low-grade
fever, weight loss, and joint stiffness. Some individuals
have the rash for years before they progress to these
symptoms, while in others the onset of symptoms is
rapid. In children the development of symptoms is
almost always gradual, making diagnosis especially
difficult.

Diagnosis
DM can be difficult to diagnose, and often the
first doctor an individual sees is a dermatologist for
treatment of the rash and then is referred to a
GALE ENCYCLOPEDIA OF MEDICINE

rheumatologist, specialist in internal medicine or neurologist when DM is suspected. Many tests may be
done to rule out other diseases before a firm diagnosis
is made. A blood test is done to measure the level of
creatine kinase. Creatine kinase is an enzyme found in
muscle tissue. When muscle is damaged, this enzyme
leaks out into the blood. An increased level of creatine
kinase in the blood suggests DM as a possible diagnosis. Another blood test may be done to test for
specific immune system antibodies. Antibodies are
proteins made in response to material the body thinks
is foreign.
An electromyogram (EMG) is a test that measures
electrical activity in muscles as they contract.
Individuals with inflammatory myopathies usually
have distinct patterns of electrical activity in the
affected muscles. However, up to 15% of people with
DM have normal electromyogram readings, so this
test is not definitive. The definitive test is a muscle
biopsy. The doctor takes a small sample of muscle
tissue and examines it under a microscope. From this
sample, the doctor can differentiate DM from other
inflammatory myopathies and other muscle wasting
diseases.

Treatment
The goal of treatment is to improve muscle
strength and allow the individual to participate in
normal daily activities. Individuals are given steroid
drugs (prednisone, corticosteroids) that suppress the
immune system. Over time, these drugs often produce
undesirable side effects, so treatment is usually begun
with a large dose, then tapered to the minimum dose
needed for maintenance. People who do not respond
well to steroid treatment may be treated with other
immunosuppressive drugs or intravenous immunoglobulin. Individuals with DM are advised to avoid
exposure to the sun, as sunlight worsens the skin rash.
Physical therapy is often helpful in keeping joints from
stiffening and freezing. Moderate exercise is also
recommended.

Alternative treatment
A healthy diet high is recommended for all individuals with supplemental protein for those with severe
muscle damage.

Prognosis
The course of DM is highly variable. In about
20% of people, the disease spontaneously goes into
remission and individuals are able to lead symptom1145

Dermatomyositis

developing cancer and should be screened for malignancies regularly.

DES exposure

KEY TERMS
Immunoglobulin—Material containing specific
antibodies to fight disease that can be injected
into an individual to fight infection.
Inflammation—An infection or irritation of a tissue.

Hashmat, Aamir and Zaineb Daud. Dermatomyositis/
Polymyositis, 16 January 2004 [cited 16 February 2005].
<http://www.emedicine.com/neuro/topic85.htm>.

Tish Davidson, A.M.

Dermatophyte infections see Ringworm

Myopathy—Relating to muscle tissue.

free lives for long periods. On the other hand, in about
5% of individuals the disease progresses to death
because of heart and lung involvement. The majority
of people continue to have some symptoms and
require long-term treatment, but their degree of daily
activity varies greatly.
Serious complications from DM include involvement of the muscles of the heart and lungs, difficulty
eating and swallowing, and a tendency to develop
cancer. This association is seen only in adults and
not in children. Individuals over age 60 are more likely
to have serious complications than younger
individuals.

Prevention
There is no known way to prevent this disease.
Resources
PERIODICALS

Koler, Ric A. and Andrew Montemarano.
‘‘Dermatomyositis.’’ American Family Physician, 24,
no. 9 (1 November 2001) 1565-1574 [cited 16 February
2005]. <http://www.aafp.org/afp/2001101/
1565.html>.
ORGANIZATIONS

American Autoimmune Related Disease Association. 22100
Gratiot Avenue, Eastpointe, East Detroit, MI 482012227. 800-598-4668. <http://www.aarda.org>.
Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson, AZ 85718-3208. 800-572-1717. <http://
www.mdausa.org>
Myositis Association. 1233 20th Street, NW, Washington,
DC 20036. 800-821-7356. <http://
www.myositis.org>.
National Organization for Rare Disorders (NORD). P. O.
Box 1968, Danbury, CT 06813-1968. 800-999-NORD.
<http://www.rarediseases.org>.
OTHER

Callen, Jeffrey P. Dermatomyositis, 5 December 2002 [cited
16 February 2005]. <http://www.emedicine.com/
derm/topic98.htm>.
1146

I DES exposure
Definition
DES (diethylstilbestrol) is a hormone that was
prescribed for pregnant women in the 1950s and
early 1960s. Many years later, doctors discovered
that the daughters of the women who received DES
were at high risk for a variety of problems, including
infertility, premature labor, and cancer of the vagina
and cervix.

Description
In the 1950s and early 1960s, several drug companies claimed that DES (diethylstilbestrol) could prevent miscarriages. DES is a synthetic hormone, related
to estrogen. Since up to 20% of all pregnancies end in
miscarriage, this seemed like an important breakthrough and DES was prescribed for many women
who had bleeding in early pregnancy. Ultimately, it
was found to have no effect on miscarriages and the
practice of prescribing DES was stopped in the 1960s.
Almost 10 years later, the daughters of women who
had taken DES during pregnancy began to develop
unusual symptoms.
Doctors discovered that when these young women
reached their teens, they were at higher risk for a
variety of problems, including:


clear cell adenocarcinoma of the vagina and cervix



infertility



premature labor and other problems in pregnancy

It is estimated that five to 10 million people in
the United States were exposed to DES between 1938
and 1971.

Causes and symptoms
DES has affected a very specific group of women.
These are women who were exposed to DES in utero
before 18 weeks of pregnancy. In other words, their
mothers must have taken DES within the first fourGALE ENCYCLOPEDIA OF MEDICINE

In the early 1970s, there was an increase in a rare
form of cancer, clear cell adenocarcinoma of the
vagina and cervix. Up until that time, doctors had
seen these cancers only in elderly women. Suddenly,
young women who had the disease appeared.
This was so unusual that researchers studied these
women to see if they had anything in common. After a
great deal of questioning and examination, it was
found that they all had one factor in common. All of
the young women had been exposed to DES in utero in
the early weeks of pregnancy.
Today, it is difficult to imagine how shocking this
discovery was. Doctors had only recently recognized
that medications and exposure to chemicals during
pregnancy could cause birth defects. This was a birth
defect that had gone undetected for almost two
decades.
Since then, doctors have studied DES daughters
very carefully. Fortunately, the risk of clear cell adenocarcinoma is actually quite low. In fact, it appears that
if a DES daughter has not developed this cancer by age
30, she will not develop it. Since all DES daughters are
now over age 30, there should be no further cases
related to DES exposure. However, there are a number
of other symptoms and problems associated with DES
exposure.


Cervix and vagina. DES daughters often have distinctive changes of the cervix and vagina that can be
seen during a pelvic exam. These changes include a
cervical hood (a vaginal fold draped over the cervix),
cockscomb cervix (an abnormally shaped cervix),
and adenosis (glandular cells normally located
within the cervix that appear on the outside of the
cervix and in the vagina).



Fallopian tubes. Some DES daughters have fallopian
tube abnormalities that lead to infertility.



Uterus. Many DES daughters have a uterus that is
abnormal in size and shape. The classic sign is the
T-shaped uterus. In the normal uterus, the cavity
(hollow space inside) is rounded. In a T-shaped
uterus, the cavity is reduced to a thin T. The abnormal shape of the inside of the uterus makes it harder
for a woman to get pregnant and leads to a higher
risk of premature labor and birth.

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cervix—The opening at the bottom of the uterus.
Colposcopy—A special examination of the cervix
using a magnifying scope. This is a procedure that
can be done in the doctor’s office.
Fallopian tubes—The tubes that carry the ovum
(egg) from the ovary to the uterus.
Pap smear—A screening test for precancerous and
cancerous cells on the cervix. This simple test is
done during a routine pelvic exam and involves
scraping cells from the cervix.

Diagnosis
Women who have been exposed to DES should
have a pelvic exam at least once a year. In addition to
the usual pelvic exam and Pap smear, DES daughters
also should have Pap smears of the vagina and, if
possible, colposcopy. During colposcopy, the doctor
looks at the cervix and vagina through a special magnifying scope. In this way, tiny areas of abnormal cells
can be seen. This procedure is easily performed in the
doctor’s office.
When DES daughters get pregnant, they may be
at high risk for premature labor and birth and should
be monitored very carefully.
Not all women who were exposed to DES develop
problems in pregnancy. However, if problems like
infertility or miscarriage occur, the doctor may recommend a special x-ray test to check the woman’s fallopian tubes and uterus. This special test is called a
hysterosalpingogram.

Treatment
There is no treatment for the abnormalities of the
fallopian tubes and uterus caused by DES exposure.
Fortunately, there are treatments that can help with
infertility and premature labor. Clear cell adenocarcinoma of the vagina or cervix must be treated with
surgery and, possibly, chemotherapy.
Resources
PERIODICALS

Kruse, Kelly, Diane Lauver, and Karen Hanson. ‘‘Clinical
Implications of DES.’’ Nurge Practitioner, July 2003:
26–29.
Morantz, Carrie, and Brian Torrey. ‘‘CDC Web site on
Diethylstilbestrol.’’ American Family Physician,
November 15, 2003: 2088.
1147

DES exposure

five months of pregnancy. It is now known that the
female reproductive organs are formed during that
time. DES appears to interfere with proper growth
and development of the uterus, cervix, vagina, and
fallopian tubes. In 2003, new research showed that
DES also was associated with increased risk of breast
cancer.

Detoxification

OTHER

Description

Centers for Disease Control and Prevention DES Web Site.
DES Update Home <http://www.cdc.gov/DES>.

Origins

Amy B. Tuteur, MD
Teresa G. Odle

Detached retina see Retinal detachment

I Detoxification
Definition
Detoxification is one of the more widely used
treatments and concepts in alternative medicine. It is
based on the principle that illnesses can be caused by
the accumulation of toxic substances (toxins) in the
body. Eliminating existing toxins and avoiding new
toxins are essential parts of the healing process.
Detoxification utilizes a variety of tests and
techniques.

Purpose
Detoxification is helpful for those patients suffering from many chronic diseases and conditions,
including allergies, anxiety, arthritis, asthma,
chronic infections, depression, diabetes, headaches,
heart disease, high cholesterol, low blood sugar
levels, digestive disorders, mental illness, and obesity. It is helpful for those with conditions that are
influenced by environmental factors, such as cancer,
as well as for those who have been exposed to high
levels of toxic materials due to accident or occupation. Detoxification therapy is useful for those suffering from allergies or immune system problems
that conventional medicine is unable to diagnose
or treat, including chronic fatigue syndrome, environmental illness/multiple chemical sensitivity, and
fibromyalgia. Symptoms for those suffering these
conditions may include unexplained fatigue,
increased allergies, hypersensitivity to common
materials, intolerance to certain foods and indigestion, aches and pains, low grade fever, headaches,
insomnia, depression, sore throats, sudden weight
loss or gain, lowered resistance to infection, general
malaise, and disability. Detoxification can be used
as a beneficial preventative measure and as a tool to
increase overall health, vitality, and resistance to
disease.
1148

Detoxification methods of healing have been used
for thousands of years. Fasting is one of the oldest
therapeutic practices in medicine. Hippocrates, the
ancient Greek known as the ‘‘Father of Western medicine,’’ recommended fasting as a means for improving
health. Ayurvedic medicine, a traditional healing system that has developed over thousands of years, utilizes detoxification methods to treat many chronic
conditions and to prevent illness.
Detoxification treatment has become one of the
cornerstones of alternative medicine. Conventional
medicine notes that environmental factors can play a
significant role in many illnesses. Environmental medicine is a field that studies exactly how those environmental factors influence disease. Conditions such as
asthma, cancer, chronic fatigue syndrome, multiple
chemical sensitivity, and many others are strongly
influenced by exposure to toxic or allergenic substances in the environment. The United States
Centers for Disease Control estimate that over 80%
of all illnesses have environmental and lifestyle causes.
Detoxification has also become a prominent treatment as people have become more aware of environmental pollution. It is estimated that one in every four
Americans suffers from some level of heavy metal
poisoning. Heavy metals, such as lead, mercury, cadmium, and arsenic, are by-products of industry.
Synthetic agriculture chemicals, many of which are
known to cause health problems, are also found in
food, air, and water. American agriculture uses nearly
10lb (4.5 kg) of pesticides per person on the food
supply each year. These toxins have become almost
unavoidable. Pesticides that are used only on crops in
the southern United States have been found in the
tissue of animals in the far north of Canada. DDT, a
cancer-causing insecticide that has been banned for
decades, is still regularly found in the fatty tissue of
animals, birds, and fish, even in extremely remote
regions such as the North Pole.
The problem of toxins in the environment is compounded because humans are at the top of the food
chain and are more likely to be exposed to an accumulation of toxic substances in the food supply. For
instance, pesticides and herbicides are sprayed on
grains that are then fed to farm animals. Toxic substances are stored in the fatty tissue of those animals.
In addition, those animals are often injected with synthetic hormones, antibiotics, and other chemicals.
When people eat meat products, they are exposed to
the full range of chemicals and additives used along
GALE ENCYCLOPEDIA OF MEDICINE

Antibiotics
Clove
Echinacea
Eucalyptus
Garlic
Myrrh
Prickly ash bark
Propolis
Wormwood
Diaphoretics/Skin
Cleaners
Boneset
Burdock root
Cayenne pepper
Elder flowers
Ginger root
Goldenseal root
Peppermint
Oregon grape root
Yellow dock

Anticatarrhals
(Help Eliminate
Mucus)

Blood Cleaners

Boneset
Echinacea
Garlic
Goldenseal root
Hyssop
Sage
Yarrow

Burdock root
Dandelion root
Echinacea
Oregon grape root
Red clover blossoms
Yellow dock root

Diuretics

Laxatives

Cleavers
Corn silk
Horsetail
Juniper berries
Parsley leaf
Uva ursi
Yarrow dock

Buckthorn
Cascara sagrada
Dandelion root
Licorice root
Rhubarb root
Senna leaf
Yellow dock

the entire agricultural chain. Detoxification specialists
call this build up of toxins bioaccumulation. They
assert that the bioaccumulation of toxic substances
over time is responsible for many physical and mental
disorders, especially ones that are increasing rapidly
(like asthma, cancer, and mental illness). As a result,
detoxification therapies are increasing in importance
and popularity.
Toxins in the body include heavy metals and various
chemicals such as pesticides, pollutants, and food additives. Drugs and alcohol have toxic effects in the body.
Toxins are produced as normal by-products in the intestines by the bacteria that break down food. The digestion
of protein also creates toxic by-products in the body.
The body has natural methods of detoxification.
Individual cells get detoxified in the lymph and circulatory system. The liver is the principle organ of
detoxification, assisted by the kidneys and intestines.
Toxins can be excreted from the body by the kidneys,
bowels, skin, and lungs. Detoxification treatments
become necessary when the body’s natural detoxification systems become overwhelmed. This can be caused
by long-term effects of improper diet, stress, overeating, sedentary lifestyles, illness, and poor health habits
in general. When a build up of toxic substances in the
body creates illness, it’s called toxemia. Some people’s
digestive tracts become unable to digest food properly,
due to years of overeating and diets that are high in fat
GALE ENCYCLOPEDIA OF MEDICINE

and processed foods and low in fiber (the average
American diet). When this happens, food cannot
pass through the digestive tract efficiently. Instead of
being digested properly or eliminated from the bowel,
food can literally rot inside the digestive tract and
produce toxic by-products. This state is known as
toxic colon syndrome or intestinal toxemia.
Detoxification therapies try to activate and assist
the body’s own detoxification processes. They also try
to eliminate additional exposure to toxins and
strengthen the body and immune system so that toxic
imbalances won’t occur in the future.
Testing for toxic substances
Detoxification specialists use a variety of tests to
determine the causes contributing to toxic conditions.
These causes include infections, allergies, addictions,
toxic chemicals, and digestive and organ dysfunction.
Blood, urine, stool, and hair analyses, as well as
allergy tests, are used to measure a variety of bodily
functions that may indicate problems. Detoxification
therapists usually have access to laboratories that specialize in sophisticated diagnostic tests for toxic
conditions.
People who have toxemia are often susceptible to
infection because their immune systems are weakened.
Infections can be caused by parasites, bacteria,
viruses, and a common yeast. Therapists will screen
patients for underlying infections that may be contributing to illness.
Liver function is studied closely with blood and
urine tests because the liver is the principle organ in the
body responsible for removing toxic compounds.
When the liver detoxifies a substance from the body,
it does so in two phases. Tests are performed that
indicate where problems may be occurring in these
phases, which may point to specific types of toxins.
Blood and urine tests can also be completed that
screen for toxic chemicals such as PCBs (environmental poisons), formaldehyde (a common preservative),
pesticides, and heavy metals. Another useful blood
test is a test for zinc deficiency, which may reveal
heavy metal poisoning. Hair analysis is used to test
for heavy metal levels in the body. Blood and urine
tests check immune system activity, and hormone
levels can also indicate specific toxic compounds. A
24-hour urine analysis, where samples are taken
around the clock, allows therapists to determine the
efficiency of the digestive tract and kidneys. Together
with stool analysis, these tests may indicate toxic
bowel syndrome and digestive system disorders.
Certain blood and urine tests may point to nutritional
1149

Detoxification

Common Herbs Used for Detoxification

Detoxification

deficiencies and proper recovery diets can be designed
for patients as well.
Detoxification therapists may also perform extensive allergy and hypersensitivity tests. Intradermal
(between layers of the skin) and sublingual (under
the tongue) allergy tests are used to determine
a patient’s sensitivity to a variety of common
substances, including formaldehyde, auto exhaust,
perfume, tobacco, chlorine, jet fuel, and other
chemicals.
Food allergies require additional tests because
these allergies often cause reactions that are
delayed for several days after the food is eaten.
The RAST (radioallergosorbent test) is a blood
test that determines the level of antibodies (immunoglobulins) in the blood after specific foods are
eaten. The cytotoxic test is a blood test that determines if certain substances affect blood cells,
including foods and chemicals. The ELISA-ACT
(enzyme-linked immunoserological assay activated
cell test) is considered to be one of the most accurate tests for allergies and hypersensitivity to foods,
chemicals, and other agents. Other tests for food
allergies are the elimination and rotation diets, in
which foods are systematically evaluated to determine the ones that are causing problems.
Detoxification therapists usually interview and
counsel patients closely to determine and correct lifestyle, occupational, psychological, and emotional factors that may also be contributing to illness.
Detoxification therapies
Detoxification therapists use a variety of healing
techniques after a diagnosis is made. The first step is to
eliminate a patient’s exposure to all toxic or allergenic
substances. These include heavy metals, chemicals,
radiation (from x rays, power lines, cell phones, computer screens, and microwaves), smog, polluted water,
foods, drugs, caffeine, alcohol, perfume, excess
noise, and stress. If mercury poisoning has been determined, the patient will be advised to have mercury
fillings from the teeth removed, preferably by a holistic
dentist.
Specific treatments are used to stimulate and
assist the body’s detoxification process. Dietary
change is immediately enacted, eliminating allergic
and unhealthy foods, and emphasizing foods that
assist detoxification
and
support
healing.
Detoxification diets are generally low in fat, high
in fiber, and vegetarian with a raw food emphasis.
Processed foods, alcohol, and caffeine are avoided.
Nutritional supplements such as vitamins, minerals,
1150

antioxidants, amino acids, and essential fatty acids
are often prescribed. Spirulina is a sea algae that is
frequently given to assist in eliminating heavy
metals. Lipotropic agents are certain vitamins and
nutrients that promote the flow of bile and fat from
the liver.
Many herbal supplements are used in detoxification therapies as well. Milk thistle extract, called silymarin, is one of the more potent herbs for detoxifying
the liver. Naturopathy, Ayurvedic medicine, and traditional Chinese medicine (TCM) recommend numerous herbal formulas for detoxification and immune
strengthening. If infections or parasites have been
found, these are treated with herbal formulas and, in
difficult cases, antibiotics.
For toxic bowel syndrome and digestive tract disorders, herbal laxatives and high fiber foods such as
psyllium seeds may be given to cleanse the digestive
tract and promote elimination. Colonics are used to
cleanse the lower intestines. Digestive enzymes are
prescribed to improve digestion, and acidophilus and
other friendly bacteria are reintroduced into the system with nutritional supplements.
Fasting is another major therapy in detoxification. Fasting is one of the quickest ways to promote
the elimination of stored toxins in the body and to
prompt the healing process. People with severe toxic
conditions are supervised closely during fasting
because the number of toxins in the body temporarily
increases as they are being released.
Chelation therapy is used by detoxification specialists to rid the body of heavy metals. Chelates are
particular substances that bind to heavy metals and
speed their elimination. Homeopathic remedies have
also been shown to be effective for removing heavy
metals.
Sweating therapies can also detoxify the body
because the skin is a major organ of elimination.
Sweating helps release those toxins that are stored
in the subcutaneous (under the skin) fat cells.
Saunas, therapeutic baths, and exercise are some of
these treatments. Body therapies may also be prescribed, including massage therapy, acupressure,
shiatsu, manual lymph drainage, and polarity therapy. These body therapies seek to improve circulatory and structural problems, reduce stress, and
promote healing responses in the body. Mind/body
therapies such as psychotherapy, counseling, and
stress management techniques may be used to heal
the psychological components of illness and to help
patients overcome their negative patterns contributing to illness.
GALE ENCYCLOPEDIA OF MEDICINE

Allergen—A foreign substance, such as mites in
house dust or animal dander, that when inhaled
causes the airways to narrow and produces symptoms of asthma.
Antibody—A protein, also called immunoglobulin,
produced by immune system cells to remove antigens (the foreign substances that trigger the
immune response).
Fibromyalgia—A condition of debilitating pain,
among other symptoms, in the muscles and the
myofascia (the thin connective tissue that surrounds muscles, bones, and organs).
Hypersensitivity—The state where even a tiny
amount of allergen can cause severe allergic
reactions.
Multiple chemical sensitivity—A condition characterized by severe and crippling allergic reactions
to commonly used substances, particularly chemicals. Also called environmental illness.

Practitioners and treatment costs

environmental toxins and making immediate dietary
and lifestyle changes may speed the detoxification
process.

Side effects
During the detoxification process, patients may
experience side effects of fatigue, malaise, aches and
pains, emotional duress, acne, headaches, allergies,
and symptoms of colds and flu. Detoxification specialists claim that these negative side effects are part of
the healing process. These reactions are sometimes
called healing crises, which are caused by temporarily
increased levels of toxins in the body due to elimination and cleansing.

Research and general acceptance
Although environmental medicine is gaining more
respect within conventional medicine, detoxification
treatment is scarcely mentioned by the medical establishment. The research that exists on detoxification is largely
testimonial, consisting of individual personal accounts
of healing without statistics or controlled scientific
experiments. In the alternative medical community,
detoxification is an essential and widely accepted treatment for many illnesses and chronic conditions.

The costs of detoxification therapies can vary
widely, depending on the number of tests and treatments required. Detoxification treatments can be
lengthy and involved since illnesses associated with
toxic conditions usually develop over many years
and may not clear up quickly. Detoxification treatments may be lengthy because they often strive
for the holistic healing of the body, mind, and
emotions.

Resources

Practitioners may be conventionally trained
medical doctors with specialties in environmental
medicine or interests in alternative treatment. The
majority of detoxification therapists are alternative
practitioners, such as naturopaths, homeopaths,
ayurvedic doctors, or traditional Chinese doctors.
Insurance coverage varies, depending on the practitioner and the treatment involved. Consumers
should review their individual insurance policies
regarding treatment coverage.

American Holistic Medical Association. 4101 Lake Boone
Trail, Suite 201, Raleigh, NC 27607. <http://www.
holisticmedicine.org/index.html>.
Cancer Prevention Coalition. 2121 West Taylor St.,
Chicago, IL 60612. (312) 996-2297.
<http:\\www.preventcancer.com>.
Center for Occupational and Environmental Medicine. 7510
Northforest Dr., North Charleston, SC 29420. (843)
572-1600. <http:\\www.coem.com>.
Northeast Center for Environmental Medicine. P.O. Box
2716, Syracuse, NY 13220. (800) 846-ONUS.
Northwest Center for Environmental Medicine. 177 NE
102nd St., Portland, OR 97220. (503) 561-0966.

Preparations
Patients can assist diagnosis and treatment by
keeping detailed diaries of their activities, symptoms,
and contact with environmental factors that may be
affecting their health. Reducing exposure to
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Alternative Therapies Magazine. P.O. Box 17969, Durham,
NC 27715. (919) 668-8825. <http://www.alternativetherapies.com>.
Journal of Occupational and Environmental Medicine. 1114
N. Arlington Heights Rd., Arlington Heights, IL 60004.
(847) 818-1800.
ORGANIZATIONS

OTHER

A Citizens Toxic Waste Manual. Greenpeace USA, 1436 U
St. NW, Washington, DC 20009. (202) 462-1177.

Douglas Dupler, MA
1151

Detoxification

KEY TERMS

Deviated septum

I Deviated septum
Definition
The nasal septum is a thin structure, separating
the two sides of the nose. If it is not in the middle of the
nose, then it is deviated.

Description
The nasal septum is composed of two parts.
Toward the back of the head the nasal septum is
rigid bone, but further forward the bone becomes
cartilage. With one finger in each nostril this cartilage
can easily be bent back and forth. If the nasal septum
is sufficiently displaced to one side, it will impede the
flow of air and mucus through the nose. This condition, called a deviated septum, can cause symptoms
and disease.

Causes and symptoms
A deviated septum can be a simple variation in
normal structure or the result of a broken nose. Any
narrowing of the nasal passageway that it causes will
threaten the drainage of secretions from the sinuses,
which must pass through the nose. It is a general rule of
medicine that when flow is obstructed, whether it is
mucus from the sinuses or bile from the gall bladder,
infection results. People with allergic rhinitis (hay fever)
are at greater risk of obstruction because their nasal
passageways are already narrowed by the swollen
membranes lining them. The result is sinusitis, which
can be acute and severe or chronic and lingering.

Diagnosis
It is easy to see that a septum is deviated. It is more
difficult to determine if that deviation needs correction. It is common for a patient to complain that he/
she can breathe through only one nostril. Then the
diagnosis is easy. A deviated septum may also contribute to snoring, sleep apnea, and other breathing
disorders.

Treatment
The definitive treatment is surgical repositioning
of the septum, accomplished by breaking it loose and
fixing it in a proper place while it heals. Decongestants
like pseudoephedrine or phenylpropanolamine will
shrink the membranes and thereby enlarge the passages. Antihistamines, nasal cortisone spray, and other
allergy treatments may also be temporarily beneficial.
1152

A close-up of person with a deviated septum. (Custom Medical
Stock Photo. Reproduced by permission.)

Alternative treatment
As a palliative, saline drops and sprays are very
helpful in loosening mucus in the obstructed side
and preventing drying in the other side, where all
the air blows. Hot peppers, such as jalapenos, can
produce enough tears and discharge to flush out a
stopped-up nose. An even more effective treatment
is called a nasal lavage, often done using a small
pot with a spout. Saline solution is poured into one
nostril and allowed to flow out the other nostril.
Then, the process is repeated in reverse. These
therapies are all useful to take care of symptoms,
but do not correct the problem. Nasospecific, a
procedure where a deflated balloon is inserted in
the nostril and inflated to a large enough degree to
adjust the septal deviation, can be an alternative to
surgery. A trained practitioner in the nasospecific
procedure is necessary.
GALE ENCYCLOPEDIA OF MEDICINE

Allergen—Any substance that irritates people sensitive (allergic) to it.
Allergic rhinitis—Swelling and inflammation of the
nasal membranes caused by sensitivity to airborne
matter like pollen or cat hair.
Saline—A salt solution in water. Normal saline has
the same salt concentration as the body, 0.9%.
Sinuses—The nasal sinuses, air-filled cavities surrounding the eyes and nose, like the nose itself are
lined with mucus-producing membranes. They
provide cleansing to the nose, resonance to the
voice, and structure to the face.
Sinusitis—Infection of the sinuses.
Sleep apnea—A condition in which breathing is
temporarily interrupted during sleep. It leads to
high blood pressure, sleepiness, and a variety of
other problems.

Prognosis
Surgical repair is curative and carries little risk.
Chronic infection can be painful and lead to complications until it is resolved. If there is continued obstruction, the infection will very likely return.

Prevention
Avoidance of virus colds, airborne dusts, air pollution, and known allergens will minimize the irritation
and swelling of the membranes lining the nasal passages.
Resources
BOOKS

Ballenger, John Jacob. Disorders of the Nose, Throat, Ear,
Head, and Neck. Philadelphia: Lea & Febiger, 1991.

J. Ricker Polsdorfer, MD

The massively increased urine output is usually
accompanied by intense thirst.

Description
The balance of fluid within the body is maintained
through a number of mechanisms. One important
chemical involved in fluid balance is called antidiuretic
hormone (ADH). ADH is produced by the pituitary, a
small gland located at the base of the brain. In a
healthy person and under normal conditions, ADH
is continuously released. ADH influences the amount
of fluid that the kidneys reabsorb into the circulatory
system and the amount of fluid that the kidneys pass
out of the body in the form of urine.
Production of ADH is regulated by the osmolality
of the circulating blood. Osmolality refers to the concentration of dissolved chemicals (such as sodium,
potassium, and chloride; together called solute) circulating in the fluid base of the blood (plasma). When
there is very little fluid compared to the concentration
of solute, the pituitary will increase ADH production.
This tells the kidneys to retain more water and to
decrease the amount of urine produced. As fluid is
retained, the concentration of solute will normalize.
At other times, when the fluid content of the blood is
high in comparison to the concentration of solute,
ADH production will decrease. The kidneys are then
free to pass an increased amount of fluid out of the
body in the urine. Again, this will allow the plasma
osmolality to return to normal.
Diabetes insipidus occurs when either the amount
of ADH produced by the pituitary is below normal
(central DI), or the kidneys’ ability to respond to
ADH is defective (nephrogenic DI). In either case, a
person with DI will pass extraordinarily large quantities of urine, sometimes reaching 10 or more liters each
day. At the same time, the patient’s blood will be very
highly concentrated, with low fluid volume and high
concentrations of solute.
DI occurs on average when a person is about 24
years old, and occurs more frequently in males than in
females.

Dextromethorphan see Cough suppressants
Causes and symptoms

I Diabetes insipidus
Definition
Diabetes insipidus (DI) is a disorder that causes
the patient to produce tremendous quantities of urine.
GALE ENCYCLOPEDIA OF MEDICINE

DI may run in families. The cause of this type of DI
is unknown. Other times, central DI can be caused by:


an injury to the head



brain surgery



cancers that have spread to the pituitary gland (most
commonly occurring with breast cancer)
1153

Diabetes insipidus

KEY TERMS

Diabetes insipidus



sarcoidosis (or other related disorders), causing
destruction of the pituitary gland



any condition or illness that causes decreased oxygen
delivery to the brain



the use of certain medications that decrease ADH
production (like the antiseizure drug phenytoin)



the excessive use of alcohol

KEY TERMS
Concentration—Refers to the amount of solute
present in a solution, compared to the total amount
of solvent.
Dilute—A solution that has comparatively more
fluid in it, relative to the quantity of solute.

Central DI may also occur in women who are
pregnant or have just given birth, and in patients
with AIDS who have suffered certain types of
brain infections. Nephrogenic DI sometimes occurs
in patients who are taking the medication lithium,
patients who have high levels of blood calcium, and
patients who are pregnant.
DI is easily confused with an entirely unrelated
disorder, psychogenic polydipsia. Polydipsia refers
to drinking large amounts of water. Psychogenic
polydipsia is a psychiatric problem that makes a
person drink huge quantities of water uncontrollably.
Symptoms of DI include extreme thirst and the
production of tremendous quantities of urine.
Patients with DI typically drink huge amounts of
water, and usually report a specific craving for cold
water. When the amount of water passed in the
urine exceeds the patient’s ability to drink ample
replacement water, the patient may begin to suffer
from symptoms of dehydration. These symptoms
include weakness, fatigue, fever, low blood pressure,
increased heart rate, dizziness, and confusion. If left
untreated, the patient could lapse into unconsciousness and die.

Diagnosis
Diagnosis should be suspected in any patient
with sudden increased thirst and urination.
Laboratory examination of urine will reveal very
dilute urine, made up mostly of water with no
solute. Examination of the blood will reveal very
concentrated blood, high in solute and low in fluid
volume.
A water deprivation test may be performed. This
test requires a patient to stop all fluid intake. The
patient is weighed just before the test begins, and
urine is collected and examined hourly. The test is
stopped when:

Osmolality—A measure of the solute-to-solvent
concentration of a solution.
Solute—Solid substances that are dissolved in
liquid in order to make a solution.



the urine is no longer changing significantly from
one sample to the next in terms of solute
concentration.

The next step of the test involves injecting a synthetic form of ADH, with one last urine sample examined 60 minutes later. Comparing plasma and urine
osmolality allows the doctor to diagnose either central
DI, nephrogenic DI, partial DI, or psychogenic
polydipsia.

Treatment
A number of medications can be given to
decrease the quantity of fluid passed out into the
urine. These include rasoprassin (Pitressin) injected
and desmopressin acetate (DDAVP) inhaled through
the nose. Other medications that may be given
include some antidiuretic drugs (chlorpropamide,
clofibrate, carbamazepine). Patients with nephrogenic DI, however, will also require special diets
that restrict the amount of solute taken in. These
patients are also treated with a type of medication
called a thiazide diuretic.

Prognosis
Uncomplicated diabetes insipidus is controllable
with adequate intake of water and most patients can
lead normal lives.
Resources
PERIODICALS



the patient has lost more than 5% of his or her
original body weight

Singer, Irwin, et al. ‘‘The Management of Diabetes Insipidus
in Adults.’’ Archives of Internal Medicine 157, no. 12
(June 23, 1997): 1293+.



the patient has reached certain limits of low blood
pressure and increased heart rate

Rosalyn Carson-DeWitt, MD

1154

GALE ENCYCLOPEDIA OF MEDICINE

Definition
Diabetes mellitus is a condition in which the pancreas no longer produces enough insulin or cells stop
responding to the insulin that is produced, so that
glucose in the blood cannot be absorbed into the
cells of the body. Symptoms include frequent urination, lethargy, excessive thirst, and hunger. The treatment includes changes in diet, oral medications, and in
some cases, daily injections of insulin.

Description
Diabetes mellitus is a chronic disease that causes
serious health complications including renal (kidney)
failure, heart disease, stroke, and blindness.
Approximately 17 million Americans have diabetes.
Unfortunately, as many as one-half are unaware they
have it.
Background
Every cell in the human body needs energy in
order to function. The body’s primary energy source
is glucose, a simple sugar resulting from the digestion
of foods containing carbohydrates (sugars and
starches). Glucose from the digested food circulates
in the blood as a ready energy source for any cells that
need it. Insulin is a hormone or chemical produced by
cells in the pancreas, an organ located behind the
stomach. Insulin bonds to a receptor site on the outside of cell and acts like a key to open a doorway into
the cell through which glucose can enter. Some of the
glucose can be converted to concentrated energy
sources like glycogen or fatty acids and saved for
later use. When there is not enough insulin produced
or when the doorway no longer recognizes the insulin
key, glucose stays in the blood rather entering the cells.
The body will attempt to dilute the high level of
glucose in the blood, a condition called hyperglycemia, by drawing water out of the cells and into the
bloodstream in an effort to dilute the sugar and excrete
it in the urine. It is not unusual for people with undiagnosed diabetes to be constantly thirsty, drink large
quantities of water, and urinate frequently as their
bodies try to get rid of the extra glucose. This creates
high levels of glucose in the urine.
At the same time that the body is trying to get rid
of glucose from the blood, the cells are starving for
glucose and sending signals to the body to eat more
food, thus making patients extremely hungry. To
GALE ENCYCLOPEDIA OF MEDICINE

Types of diabetes mellitus
Type I diabetes, sometimes called juvenile diabetes, begins most commonly in childhood or adolescence. In this form of diabetes, the body produces little
or no insulin. It is characterized by a sudden onset and
occurs more frequently in populations descended from
Northern European countries (Finland, Scotland,
Scandinavia) than in those from Southern European
countries, the Middle East, or Asia. In the United
States, approximately three people in 1,000 develop
Type I diabetes. This form also is called insulin-dependent diabetes because people who develop this type
need to have daily injections of insulin.
Brittle diabetics are a subgroup of Type I where
patients have frequent and rapid swings of blood sugar
levels between hyperglycemia (a condition where there
is too much glucose or sugar in the blood) and hypoglycemia (a condition where there are abnormally low
levels of glucose or sugar in the blood). These patients
may require several injections of different types of
insulin during the day to keep the blood sugar level
within a fairly normal range.
The more common form of diabetes, Type II,
occurs in approximately 3–5% of Americans under
50 years of age, and increases to 10–15% in those
over 50. More than 90% of the diabetics in the
United States are Type II diabetics. Sometimes called
age-onset or adult-onset diabetes, this form of diabetes occurs most often in people who are overweight
and who do not exercise. It is also more common in
people of Native American, Hispanic, and AfricanAmerican descent. People who have migrated to
Western cultures from East India, Japan, and
Australian Aboriginal cultures also are more likely to
develop Type II diabetes than those who remain in
their original countries.
Type II is considered a milder form of diabetes
because of its slow onset (sometimes developing over
the course of several years) and because it usually can
be controlled with diet and oral medication. The
consequences of uncontrolled and untreated Type II
diabetes, however, are the just as serious as those for
Type I. This form is also called noninsulin-dependent
1155

Diabetes mellitus

I Diabetes mellitus

provide energy for the starving cells, the body also
tries to convert fats and proteins to glucose. The
breakdown of fats and proteins for energy causes
acid compounds called ketones to form in the blood.
Ketones also will be excreted in the urine. As ketones
build up in the blood, a condition called ketoacidosis
can occur. This condition can be life threatening if left
untreated, leading to coma and death.

Diabetes mellitus

diabetes, a term that is somewhat misleading. Many
people with Type II diabetes can control the condition
with diet and oral medications, however, insulin injections are sometimes necessary if treatment with diet
and oral medication is not working.
Another form of diabetes called gestational diabetes can develop during pregnancy and generally
resolves after the baby is delivered. This diabetic condition develops during the second or third trimester of
pregnancy in about 2% of pregnancies. In 2004, incidence of gestational diabetes were reported to have
increased 35% in 10 years. Children of women with
gestational diabetes are more likely to be born prematurely, have hypoglycemia, or have severe jaundice at
birth. The condition usually is treated by diet, however, insulin injections may be required. These women
who have diabetes during pregnancy are at higher risk
for developing Type II diabetes within 5–10 years.
Diabetes also can develop as a result of pancreatic
disease, alcoholism, malnutrition, or other severe illnesses that stress the body.

Causes and symptoms
Causes
The causes of diabetes mellitus are unclear, however, there seem to be both hereditary (genetic factors
passed on in families) and environmental factors
involved. Research has shown that some people who
develop diabetes have common genetic markers. In
Type I diabetes, the immune system, the body’s
defense system against infection, is believed to be triggered by a virus or another microorganism that
destroys cells in the pancreas that produce insulin. In
Type II diabetes, age, obesity, and family history of
diabetes play a role.
In Type II diabetes, the pancreas may produce
enough insulin, however, cells have become resistant to
the insulin produced and it may not work as effectively.
Symptoms of Type II diabetes can begin so gradually
that a person may not know that he or she has it. Early
signs are lethargy, extreme thirst, and frequent urination. Other symptoms may include sudden weight loss,
slow wound healing, urinary tract infections, gum disease, or blurred vision. It is not unusual for Type II
diabetes to be detected while a patient is seeing a doctor
about another health concern that is actually being
caused by the yet undiagnosed diabetes.
Individuals who are at high risk of developing
Type II diabetes mellitus include people who:


are obese (more than 20% above their ideal body
weight)

1156



have a relative with diabetes mellitus



belong to a high-risk ethnic population (AfricanAmerican, Native American, Hispanic, or Native
Hawaiian)



have been diagnosed with gestational diabetes or
have delivered a baby weighing more than 9 lbs (4 kg)



have high blood pressure (140/90 mmHg or above)



have a high density lipoprotein cholesterol level less
than or equal to 35 mg/dL and/or a triglyceride level
greater than or equal to 250 mg/dL



have had impaired glucose tolerance or impaired
fasting glucose on previous testing

Several common medications can impair the
body’s use of insulin, causing a condition known as
secondary diabetes. These medications include treatments for high blood pressure (furosemide, clonidine,
and thiazide diuretics), drugs with hormonal activity
(oral contraceptives, thyroid hormone, progestins, and
glucocorticorids), and the anti-inflammation drug
indomethacin. Several drugs that are used to treat
mood disorders (such as anxiety and depression) also
can impair glucose absorption. These drugs include
haloperidol, lithium carbonate, phenothiazines,
tricyclic antidepressants, and adrenergic agonists.
Other medications that can cause diabetes symptoms
include isoniazid, nicotinic acid, cimetidine, and
heparin. A 2004 study found that low levels of the
essential mineral chromium in the body may be linked
to increased risk for diseases associated with insulin
resistance.
Symptoms
Symptoms of diabetes can develop suddenly (over
days or weeks) in previously healthy children or adolescents, or can develop gradually (over several years)
in overweight adults over the age of 40. The classic
symptoms include feeling tired and sick, frequent
urination, excessive thirst, excessive hunger, and
weight loss.
Ketoacidosis, a condition due to starvation or uncontrolled diabetes, is common in Type I diabetes. Ketones
are acid compounds that form in the blood when the
body breaks down fats and proteins. Symptoms include
abdominal pain, vomiting, rapid breathing, extreme
lethargy, and drowsiness. Patients with ketoacidosis will
also have a sweet breath odor. Left untreated, this condition can lead to coma and death.
With Type II diabetes, the condition may not
become evident until the patient presents for medical
treatment for some other condition. A patient may
have heart disease, chronic infections of the gums
GALE ENCYCLOPEDIA OF MEDICINE

Diabetes mellitus

and urinary tract, blurred vision, numbness in the feet
and legs, or slow-healing wounds. Women may experience genital itching.

Diagnosis
Diabetes is suspected based on symptoms. Urine
tests and blood tests can be used to confirm a diagnose
of diabetes based on the amount of glucose found.
Urine can also detect ketones and protein in the
urine that may help diagnose diabetes and assess
how well the kidneys are functioning. These tests also
can be used to monitor the disease once the patient is
on a standardized diet, oral medications, or insulin.
Urine tests
Clinistix and Diastix are paper strips or dipsticks
that change color when dipped in urine. The test strip
is compared to a chart that shows the amount of
glucose in the urine based on the change in color.
The level of glucose in the urine lags behind the level
of glucose in the blood. Testing the urine with a test
stick, paper strip, or tablet that changes color when
sugar is present is not as accurate as blood testing,
however it can give a fast and simple reading.
Ketones in the urine can be detected using similar
types of dipstick tests (Acetest or Ketostix).
Ketoacidosis can be a life-threatening situation in Type
I diabetics, so having a quick and simple test to detect
ketones can assist in establishing a diagnosis sooner.
Another dipstick test can determine the presence
of protein or albumin in the urine. Protein in the urine
can indicate problems with kidney function and can be
used to track the development of renal failure. A more
sensitive test for urine protein uses radioactively
tagged chemicals to detect microalbuminuria, small
amounts of protein in the urine, that may not show
up on dipstick tests.
Blood tests
FASTING GLUCOSE TEST. Blood is drawn from a
vein in the patient’s arm after a period at least eight
hours when the patient has not eaten, usually in the
morning before breakfast. The red blood cells are
separated from the sample and the amount of glucose
is measured in the remaining plasma. A plasma level of
7.8 mmol/L (200 mg/L) or greater can indicate diabetes. The fasting glucose test is usually repeated on
another day to confirm the results.
POSTPRANDIAL GLUCOSE TEST. Blood is taken
right after the patient has eaten a meal.

GALE ENCYCLOPEDIA OF MEDICINE

Wrinkled, dehydrated skin of a person in a diabetic coma.
Untreated diabetes mellitus results in elevated blood glucose
levels, causing a variety of symptoms that can culminate in a
diabetic coma. (Photo Researchers, Inc. Reproduced by
permission.)

ORAL GLUCOSE TOLERANCE TEST. Blood samples
are taken from a vein before and after a patient drinks
a thick, sweet syrup of glucose and other sugars. In a
non-diabetic, the level of glucose in the blood goes up
immediately after the drink and then decreases gradually as insulin is used by the body to metabolize, or
absorb, the sugar. In a diabetic, the glucose in the
blood goes up and stays high after drinking the sweetened liquid. A plasma glucose level of 11.1 mmol/L
(200 mg/dL) or higher at two hours after drinking the
syrup and at one other point during the two-hour test
period confirms the diagnosis of diabetes.

A diagnosis of diabetes is confirmed if there are
symptoms of diabetes and a plasma glucose level of at
least 11.1 mmol/L, a fasting plasma glucose level of at
least 7 mmol/L; or a two-hour plasma glucose level
of at least 11.1 mmol/L during an oral glucose tolerance test.
Home blood glucose monitoring kits are available
so patients with diabetes can monitor their own levels.
A small needle or lancet is used to prick the finger and
a drop of blood is collected and analyzed by a monitoring device. Some patients may test their blood glucose levels several times during a day and use this
information to adjust their doses of insulin.

Treatment
There is currently no cure for diabetes. The condition, however, can be managed so that patients can
live a relatively normal life. Treatment of diabetes
focuses on two goals: keeping blood glucose within
normal range and preventing the development of longterm complications. Careful monitoring of diet,
1157

Diabetes mellitus

exercise, and blood glucose levels are as important as
the use of insulin or oral medications in preventing
complications of diabetes. In 2003, the American
Diabetes Association updated its Standards of Care
for the management of diabetes. These standards help
manage health care providers in the most recent
recommendations for diagnosis and treatment of the
disease.
Dietary changes
Diet and moderate exercise are the first treatments
implemented in diabetes. For many Type II diabetics,
weight loss may be an important goal in helping them
to control their diabetes. A well-balanced, nutritious
diet provides approximately 50–60% of calories from
carbohydrates, approximately 10–20% of calories
from protein, and less than 30% of calories from fat.
The number of calories required by an individual
depends on age, weight, and activity level. The calorie
intake also needs to be distributed over the course of
the entire day so surges of glucose entering the blood
system are kept to a minimum.
Keeping track of the number of calories provided
by different foods can become complicated, so
patients usually are advised to consult a nutritionist
or dietitian. An individualized, easy to manage diet
plan can be set up for each patient. Both the American
Diabetes Association and the American Dietetic
Association recommend diets based on the use of
food exchange lists. Each food exchange contains a
known amount of calories in the form of protein, fat,
or carbohydrate. A patient’s diet plan will consist of a
certain number of exchanges from each food category
(meat or protein, fruits, breads and starches, vegetables, and fats) to be eaten at meal times and as snacks.
Patients have flexibility in choosing which foods they
eat as long as they stick with the number of exchanges
prescribed.
For many Type II diabetics, weight loss is an
important factor in controlling their condition. The
food exchange system, along with a plan of moderate
exercise, can help them lose excess weight and improve
their overall health.
Oral medications
Oral medications are available to lower blood glucose in Type II diabetics. In 1990, 23.4 outpatient prescriptions for oral antidiabetic agents were dispensed.
By 2001, the number had increased to 91.8 million prescriptions. Oral antidiabetic agents accounted for more
than $5 billion dollars in worldwide retail sales per year
in the early twenty-first century and were the fastest1158

growing segment of diabetes drugs. The drugs first prescribed for Type II diabetes are in a class of compounds
called sulfonylureas and include tolbutamide, tolazamide, acetohexamide, and chlorpropamide. Newer
drugs in the same class are now available and include
glyburide, glimeperide, and glipizide. How these drugs
work is not well understood, however, they seem to
stimulate cells of the pancreas to produce more insulin.
New medications that are available to treat diabetes
include metformin, acarbose, and troglitizone. The
choice of medication depends in part on the individual
patient profile. All drugs have side effects that may make
them inappropriate for particular patients. Some for
example, may stimulate weight gain or cause stomach
irritation, so they may not be the best treatment for
someone who is already overweight or who has stomach
ulcers. Others, like metformin, have been shown to have
positive effects such as reduced cardiovascular mortality, but but increased risk in other situations. While these
medications are an important aspect of treatment for
Type II diabetes, they are not a substitute for a well
planned diet and moderate exercise. Oral medications
have not been shown effective for Type I diabetes, in
which the patient produces little or no insulin.
Constant advances are being made in development of new oral medications for persons with diabetes. In 2003, a drug called Metaglip combining
glipizide and metformin was approved in a dingle
tablet. Along with diet and exercise, the drug was
used as initial therapy for Type 2 diabetes. Another
drug approved by the U.S. Food and Drug
Administration (FDA) combines metformin and rosiglitazone (Avandia), a medication that increases muscle cells’ sensitivity to insulin. It is marketed under the
name Avandamet. So many new drugs are under
development that it is best to stay in touch with a
physician for the latest information; physicians can
find the best drug, diet and exercise program to fit an
individual patient’s need.
Insulin
Patients with Type I diabetes need daily injections
of insulin to help their bodies use glucose. The amount
and type of insulin required depends on the height,
weight, age, food intake, and activity level of the individual diabetic patient. Some patients with Type II
diabetes may need to use insulin injections if their
diabetes cannot be controlled with diet, exercise, and
oral medication. Injections are given subcutaneously,
that is, just under the skin, using a small needle and
syringe. Injection sites can be anywhere on the body
where there is looser skin, including the upper arm,
abdomen, or upper thigh.
GALE ENCYCLOPEDIA OF MEDICINE

Regular insulin is fast-acting and starts to work
within 15–30 minutes, with its peak glucose-lowering
effect about two hours after it is injected. Its effects last
for about four to six hours. NPH (neutral protamine
Hagedorn) and Lente insulin are intermediate-acting,
starting to work within one to three hours and lasting
up to 18–26 hours. Ultra-lente is a long-acting form of
insulin that starts to work within four to eight hours
and lasts 28–36 hours.
Hypoglycemia, or low blood sugar, can be caused
by too much insulin, too little food (or eating too late to
coincide with the action of the insulin), alcohol consumption, or increased exercise. A patient with symptoms of hypoglycemia may be hungry, cranky,
confused, and tired. The patient may become sweaty
and shaky. Left untreated, the patient can lose consciousness or have a seizure. This condition is sometimes called an insulin reaction and should be treated by
giving the patient something sweet to eat or drink like a
candy, sugar cubes, juice, or another high sugar snack.
Surgery
Transplantation of a healthy pancreas into a diabetic patient is a successful treatment, however, this
transplant is usually done only if a kidney transplant is
performed at the same time. Although a pancreas
transplant is possible, it is not clear if the potential
benefits outweigh the risks of the surgery and drug
therapy needed.

Alternative treatment
Since diabetes can be life-threatening if not properly managed, patients should not attempt to treat this
condition without medicial supervision. A variety of
alternative therapies can be helpful in managing the
symptoms of diabetes and supporting patients with
the disease. Acupuncture can help relieve the pain
associated with diabetic neuropathy by stimulation of
GALE ENCYCLOPEDIA OF MEDICINE

cetain points. A qualified practitioner should be consulted. Herbal remedies also may be helpful in managing diabetes. Although there is no herbal substitute
for insulin, some herbs may help adjust blood sugar
levels or manage other diabetic symptoms. Some
options include:


fenugreek (Trigonella foenum-graecum) has been
shown in some studies to reduce blood insulin and
glucose levels while also lowering cholesterol



bilberry (Vaccinium myrtillus) may lower blood glucose levels, as well as helping to maintain healthy
blood vessels



garlic (Allium sativum) may lower blood sugar and
cholesterol levels



onions (Allium cepa) may help lower blood glucose
levels by freeing insulin to metabolize them



cayenne pepper (Capsicum frutescens) can help
relieve pain in the peripheral nerves (a type of diabetic neuropathy)



gingko (Gingko biloba) may maintain blood flow to
the retina, helping to prevent diabetic retinopathy

Any therapy that lowers stress levels also can be
useful in treating diabetes by helping to reduce insulin
requirements. Among the alternative treatments that
aim to lower stress are hypnotherapy, biofeedback,
and meditation.

Prognosis
Uncontrolled diabetes is a leading cause of blindness, end-stage renal disease, and limb amputations. It
also doubles the risks of heart disease and increases the
risk of stroke. Eye problems including cataracts, glaucoma, and diabetic retinopathy also are more common
in diabetics.
Diabetic peripheral neuropathy is a condition where
nerve endings, particularly in the legs and feet, become
less sensitive. Diabetic foot ulcers are a particular problem since the patient does not feel the pain of a blister,
callous, or other minor injury. Poor blood circulation in
the legs and feet contribute to delayed wound healing.
The inability to sense pain along with the complications
of delayed wound healing can result in minor injuries,
blisters, or callouses becoming infected and difficult to
treat. In cases of severe infection, the infected tissue
begins to break down and rot away. The most serious
consequence of this condition is the need for amputation
of toes, feet, or legs due to severe infection.
Heart disease and kidney disease are common
complications of diabetes. Long-term complications
1159

Diabetes mellitus

Purified human insulin is most commonly used,
however, insulin from beef and pork sources also are
available. Insulin may be given as an injection of a single
dose of one type of insulin once a day. Different types of
insulin can be mixed and given in one dose or split into
two or more doses during a day. Patients who require
multiple injections over the course of a day may be able
to use an insulin pump that administers small doses of
insulin on demand. The small battery-operated pump is
worn outside the body and is connected to a needle that
is inserted into the abdomen. Pumps can be programmed to inject small doses of insulin at various
times during the day, or the patient may be able to adjust
the insulin doses to coincide with meals and exercise.

Diabetes mellitus

KEY TERMS
Cataract—A condition where the lens of the eye
becomes cloudy.
Diabetic peripheral neuropathy—A condition
where the sensitivity of nerves to pain, temperature,
and pressure is dulled, particularly in the legs
and feet.
Diabetic retinopathy—A condition where the tiny
blood vessels to the retina, the tissues that sense
light at the back of the eye, are damaged, leading to
blurred vision, sudden blindness, or black spots,
lines, or flashing lights in the field of vision.
Glaucoma—A condition where pressure within the
eye causes damage to the optic nerve, which sends
visual images to the brain.
Hyperglycemia—A condition where there is too
much glucose or sugar in the blood.
Hypoglycemia—A condition where there is too
little glucose or sugar in the blood.
Insulin—A hormone or chemical produced by the
pancreas, insulin is needed by cells of the body in
order to use glucose (sugar), the body’s main source
of energy.
Ketoacidosis—A condition due to starvation or
uncontrolled Type I diabetes. Ketones are acid
compounds that form in the blood when the body
breaks down fats and proteins. Symptoms include
abdominal pain, vomiting, rapid breathing,
extreme tiredness, and drowsiness.
Kidney dialysis—A process where blood is filtered
through a dialysis machine to remove waste products that would normally be removed by the kidneys. The filtered blood is then circulated back into
the patient. This process also is called renal
dialysis.
Pancreas—A gland located behind the stomach
that produces insulin.

may include the need for kidney dialysis or a kidney
transplant due to kidney failure.
Babies born to diabetic mothers have an increased
risk of birth defects and distress at birth.

Prevention
Research continues on diabetes prevention and
improved detection of those at risk for developing
diabetes. While the onset of Type I diabetes is
1160

unpredictable, the risk of developing Type II diabetes
can be reduced by maintaining ideal weight and exercising regularly. The physical and emotional stress of
surgery, illness, pregnancy, and alcoholism can
increase the risks of diabetes, so maintaining a healthy
lifestyle is critical to preventing the onset of Type II
diabetes and preventing further complications of the
disease.
Resources
PERIODICALS

Crutchfield, Diane B. ‘‘Oral Antidiabetic Agents: Back to
the Basics.’’ Geriatric Times, May 1, 2003: 20.
‘‘Gestational Diabetes Increases 35% in 10 Years.’’ Health &
Medicine Week, March 22, 2004: 220.
Kordella, Terri. ‘‘New Combo Pills.’’ Diabetes Forecast,
March 2003: 42.
‘‘New Drugs.’’ Drug Topics, November 18, 2002: 73.
‘‘Research: Lower Chromium Levels Linked to Increased
Risk of Disease.’’ Diabetes Week, March 29, 2004: 21.
‘‘Standards of Medical Care for Patients with Diabetes
Mellitus: American Diabetes Association.’’ Clinical
Diabetes, Winter 2003: 27.
‘‘Wider Metformin Use Recommended.’’ Chemist &
Druggist, January 11, 2003: 24.
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.
American Dietetic Association. 216 W. Jackson Blvd.,
Chicago, IL 60606-6995. (312) 899-0040. <http://
www.eatright.org>.
Juvenile Diabetes Foundation. 120 Wall St., 19th Floor,
New York, NY 10005. (800) 533-2873. <http://
www.jdf.org>.
National Diabetes Information Clearinghouse. 1
Information Way, Bethesda, MD 20892-3560. (800)
860-8747. Ndic@info.niddk.nih.gov. <http://
www.niddk.nih.gov/health/diabetes/ndic.htm>.
OTHER

Centers for Disease Control. <http://www.cdc.gov/
nccdphp/ddt/ddthome.htm>.
‘‘Insulin-Dependent Diabetes.’’ National Institute of
Diabetes and Digestive and Kidney Diseases. National
Institutes of Health, NIH Publication No.94-2098.
‘‘Noninsulin-Dependent Diabetes.’’ National Institute of
Diabetesand Digestive and Kidney Diseases. National
Institutes of Health, NIH Publication No.92-241.

Altha Roberts Edgren
Teresa G. Odle

Diabetic control index see Glycosylated
hemoglobin test
GALE ENCYCLOPEDIA OF MEDICINE

Diabetic foot infections

I Diabetic foot infections
Definition
Diabetic foot infections are infections that can
develop in the skin, muscles, or bones of the foot as a
result of the nerve damage and poor circulation that is
associated with diabetes.

Description
People who have diabetes have a greater-thanaverage chance of developing foot infections.
Because a person who has diabetes may not feel foot
pain or discomfort, problems can remain undetected
until fever, weakness, or other signs of systemic infection appear. As a result, even minor irritations occur
more often, heal more slowly, and are more likely to
result in serious health problems.
With diabetes, foot infections occur more frequently because the disease causes nervous system
changes and poor circulation. Because the nerves
that control sweating no longer work, the skin of
the feet can become very dry and cracked, and
calluses tend to occur more frequently and build
up faster. If not trimmed regularly, these calluses
can turn into open sores or ulcers. Because diabetic
nerve damage can cause a loss of sensation (neuropathy), if the feet are not regularly inspected, an
ulcer can quickly become infected and, if not treated, may result in the death of tissue (gangrene) or
amputation.
The risk of infection is greatest for people who are
over the age of 60 and for those who have one or more
of the following:


poorly controlled diabetes



foot ulcers



laser treatment for changes in the retina



kidney or vascular disease



loss of sensation (neuropathy)

Causes and symptoms
Bacteria can cause an infection through small
cracks (fissures) that can develop in the dry skin
around the heel and on other parts of the foot or
through corns, calluses, blisters, hangnails, or ulcers.
If not treated, the bacterial infection can destroy skin,
tissue, and bone or spread throughout the body.
Common sites of diabetic foot infections include
the following:
GALE ENCYCLOPEDIA OF MEDICINE

Persons with diabetes often suffer from foot ulcers, as shown
above. (Custom Medical Stock Photo. Reproduced by
permission.)



blisters, corns, or callouses that bleed beneath the skin



bunions, hammertoes, or other abnormalities in the
bones of the foot



scar tissue that has grown over the site of an earlier
infection



foot ulcers caused by pressure, nerve damage, or
poor circulation (Ulcers occur most often over the
ball of the foot, on the bottom of the big toe, or on
the sides of the foot due to poorly fitting shoes.)



injuries that tear or puncture the skin

Diagnosis
A physician who specializes in the treatment of the
foot (podiatrist) or the doctor who normally treats the
patient’s diabetes will treat the infection. An x ray of
the foot will be taken to determine whether the bone
has become infected. A sample from the wound will
be cultured to identify the organism that is causing the
infection so that the appropriate antibiotic can
be selected.

Treatment
From the results of the culture, the appropriate
antibiotic will be prescribed. Any dead or infected
tissue will be surgically removed and, if necessary, a
cast and/or special shoes may be used to protect the
area. In addition, the patient will be instructed to keep
off their feet. If the ulcer does not heal, the physician
may perform surgery to increase blood flow to the
foot. It is also important for the patient to practice
good diabetes control and keep blood glucose levels
from getting too high.
1161

Diabetic ketoacidosis

KEY TERMS
Fissure—A deep crack.
Neuropathy—An abnormality of the nerves outside
the brain and spinal cord.

Juvenile Diabetes Foundation. 120 Wall St., 19th Floor,
New York, NY 10005. (800) 533-2873. <http://
www.jdf.org>.
National Diabetes Information Clearinghouse. 1
Information Way, Bethesda, MD 20892-3560. (800)
860-8747. <http://www.niddk.nih.gov/health/
diabetes/ndic.htm>.

Ulcer—A sore or lesion.
Maureen Haggerty

Alternative treatment
Acupuncture and vitamin C can boost the body’s
infection-fighting ability. A variety of other vitamins
and herbs may improve general health and diabetes
control. Because diabetes is a potentially deadly disease, it can be dangerous to try alternative approaches
without a doctor’s approval or without consulting a
trained practitioner of alternative medicine.

I Diabetic ketoacidosis
Definition
Diabetic ketoacidosis is a dangerous complication
of diabetes mellitus in which the chemical balance of
the body becomes far too acidic.

Prognosis
Without proper treatment, diabetic foot infections can lead to serious illness, gangrene, amputation,
and even death if the infection spreads throughout the
body. If treated properly and the patient practices
good foot care, the prognosis is generally optimistic.

Prevention
There are many things that a diabetic individual
can do to prevent the occurrence of foot infections,
including the following:


control blood glucose and do not allow it to get too high



avoid smoking



keep blood pressure and cholesterol under control



exercise to stimulate blood flow



keep feet clean, dry, and warm



check your feet every day for blisters, scratches, and
skin that is hard, broken, inflamed, or feels hot or
cold when touched



after bathing, carefully dry feet and apply thin coat
of petroleum jelly or hand cream to prevent dry skin
from cracking



use a pumice stone and emery board to trim calluses



do not neglect an ulcer, should one develop

Resources
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.
1162

Description
Diabetic ketoacidosis (DKA) always results from
a severe insulin deficiency. Insulin is the hormone
secreted by the body to lower the blood sugar levels
when they become too high. Diabetes mellitus is the
disease resulting from the inability of the body to
produce or respond properly to insulin, required by
the body to convert glucose to energy. In childhood
diabetes, DKA complications represent the leading
cause of death, mostly due to the accumulation of
abnormally large amounts of fluid in the brain (cerebral edema). DKA combines three major features:
hyperglycemia, meaning excessively high blood sugar
kevels; hyperketonemia, meaning an overproduction
of ketones by the body; and acidosis, meaning that the
blood has become too acidic.
Insulin deficiency is responsible for all three conditions: the body glucose goes largely unused since
most cells are unable to transport glucose into the
cell without the presence of insulin; this condition
makes the body use stored fat as an alternative source
instead of the unavailable glucose for energy, a process
that produces acidic ketones, which build up because
they require insulin to be broken down. The presence
of excess ketones in the bloodstream in turn causes the
blood to become more acidic than the body tissues,
which creates a toxic condition.

Causes and symptoms
DKA is most commonly seen in individuals with
type I diabetes, under 19 years of age and is usually
GALE ENCYCLOPEDIA OF MEDICINE

Acidosis—A condition that causes the pH of the
blood to drop and become more acidic.
Diabetes mellitus—Disease characterized by the
inability of the body to produce or respond properly
to insulin, required by the body to convert glucose to
energy.
Edema—The presence of abnormally large amounts
of fluid in the intercellular tissue spaces of the body.
Glucose—The type of sugar found in the blood.
Hyperglycemia—Condition characterized by excessively high levels of glucose in the blood, and occurs
when the body does not have enough insulin or
cannot use the insulin it does have to turn glucose
into energy. Hyperglycemia is often indicative of
diabetes that is out of control.
Hyperketonemia—Condition characterized by an
overproduction of ketones by the body.
Hypoglycemia—Lower than normal levels of glucose
in the blood.
Hypokalemia—A deficiency of potassium in the
blood.
Insulin—A hormone secreted by the pancreas in
response to high blood sugar levels that induces
hypoglycemia. Insulin regulates the body’s use of

caused by the interruption of their insulin treatment or by
acute infection or trauma. A small number of people with
type II diabetes also experience ketoacidosis, but this is
rare given the fact that type II diabetics still produce some
insulin naturally. When DKA occurs in type II patients,
it is usually caused by a decrease in food intake and an
increased insulin deficiency due to hyperglycemia.
Some common DKA symptoms include:


high blood sugar levels



frequent urination (polyuria) and thirst



fatigue and lethargy



nausea



vomiting



abdominal pain



fruity odor to breath



rapid, deep breathing



muscle stiffness or aching



coma

GALE ENCYCLOPEDIA OF MEDICINE

glucose and the levels of glucose in the blood by
acting to open the cells so that they can intake
glucose.
Ketones—Poisonous acidic chemicals produced by
the body when fat instead of glucose is burned for
energy. Breakdown of fat occurs when not enough
insulin is present to channel glucose into body cells.
Lactic acidosis—A serious condition caused by the
build up of lactic acid in the blood, causing it to
become excessively acidic. Lactic acid is a byproduct of glucose metabolism.
Metabolism—The sum of all chemical reactions that
occur in the body resulting in growth, transformation
of foodstuffs into energy, waste elimination, and
other bodily functions.
Polyuria—Excessive secretion of urine.
Type I diabetes—Also called juvenile diabetes. Type
I diabetes typically begins early in life. Affected individuals have a primary insulin deficiency and must
take insulin injections.
Type II diabetes—Type II diabetes is the most common form of diabetes and usually appears in middle
aged adults. It is often associated with obesity and
may be delayed or controlled with diet and exercise.

Diagnosis
Diagnosis requires the demonstration of hyperglycemia, hyperketonemia, and acidosis. DKA is
established if the patient’s urine or blood is strongly
positive for glucose and ketones. Normal glucose
levels in a non-diabetic person on average range from
80–110 mg/dl. A person with diabetes will typically
fluctuate outside those parameters. DKA glucose
levels exceed 250 mg/dl and can reach 400 to 800 mg/
dL. A low serum bicarbonate level (usually below 15
mEq/L) is also present, indicative of acidosis.
A blood test or urinalysis can quickly determine
the concentration of glucose in the bloodstream. Test
strips are available to patients commercially can submerge in urine to detect the presence or concentration
of ketones.

Treatment
Ketoacidosis is treated under medical supervision
and usually in a hospital setting.
1163

Diabetic ketoacidosis

KEY TERMS

Diabetic neuropathy

Basic treatment includes:


administering insulin to correct the hyperglycemia
and hyperketonemia



replacing fluids lost through excessive urination and
vomiting intravenously



balancing electrolytes to re-establish the chemical
equilibrium of the blood and prevent potassium deficiency (hypokalemia) during treatment



treatment for any associated bacterial infection

Prognosis
With proper medical attention, DKA is almost
always successfully treated. The DKA mortality rate is
about 10%. Coma on admission adversely affects the
prognosis. The major causes of death are circulatory
collapse, hypokalemia, infection, and cerebral edema.

Prevention
Once diabetes has been diagnosed, prevention measures to avoid DKA include regular monitoring of
blood glucose, administration of insulin, and lifestyle
maintenance. Glucose monitoring is especially important during periods of stress, infection, and trauma when
glucose concentrations typically increase as a response
to these situations. Ketone tests should also be performed during these periods or when glucose is elevated.
Resources
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) DIABETES
(800-342-2383). <http://www.diabetes.org/>.
Juvenile Diabetes Foundation. 120 Wall St., 19th Floor,
New York, NY 10005. (800) 533-CURE. <http://
www.jdf.org/>.
National Institute of Diabetes and Digestive and Kidney
Disorders (NIDDK). 31 Center Drive, MSC 2560,
Bethesda, MD 20892-2560. <http://
www.niddk.nih.gov>.

Gary Gilles

I Diabetic neuropathy
Definition
Diabetic neuropathy is a nerve disorder caused by
diabetes mellitus. Diabetic neuropathy may be diffuse,
1164

affecting several parts of the body, or focal, affecting a
specific nerve and part of the body.

Description
The nervous system consists of two major divisions: the central nervous systems (CNS) which
includes the brain, the cranial nerves, and the spinal
cord, and the peripheral nervous system (PNS) which
includes the nerves that link the CNS with the sensory
organs, muscles, blood vessels, and glands of the body.
These peripheral nerves are either motor, meaning
that they are involved in motor activity such as walking, or sensory, meaning that they carry sensory information back to the CNS. The PNS also works with the
CNS to regulate involuntary (autonomic) processes
such as breathing, heartbeat, blood pressure, etc.
There are two types of diffuse diabetic neuropathy
that affect different nervous system functions. Diffuse
peripheral neuropathy primarily affects the limbs,
damaging the nerves of the feet and hands.
Autonomic neuropathy is the other form of diffuse
neuropathy and it affects the heart and other internal
organs.
Focal—or localized—diabetic neuropathy affects
specific nerves, most commonly in the torso, leg, or head.
Diabetic neuropathy can lead to muscular weakness, loss of feeling or sensation, and loss of autonomic functions such as digestion, erection, bladder
control, and sweating among others.
The longer a person has diabetes, the more likely
the development of one or more forms of neuropathy.
Approximately 60–70% of patients with diabetes have
neuropathy, but only about 5% will experience painful symptoms.

Causes and symptoms
The exact cause of diabetic neuropathy is not
known. Researchers believe that the process of nerve
damage is related to high glucose concentrations in the
blood that could cause chemical changes in nerves,
disrupting their ability to effectively send messages.
High blood glucose is also known to damage the
blood vessels that carry oxygen and other nutrients
to the nerves. In addition, some people may have a
genetic predisposition to develop neuropathy.
There is a wide range of symptoms associated with
diabetic neuropathy, and they depend on which nerves
and parts of the body are affected and also on the type
of neuropathy present. Some patients have very mild
symptoms, while others are severely disabled.
GALE ENCYCLOPEDIA OF MEDICINE



numbness and feelings of tingling or burning



insensitivity to pain



needle-like jabs of pain



extreme sensitivity to touch



loss of balance and coordination

KEY TERMS
Central nervous system (CNS)—Part of the nervous
system consisting of the brain, cranial nerves, and
spinal cord. The brain is the center of higher processes, such as thought and emotion, and is responsible for the coordination and control of bodily
activities and the interpretation of information from
the senses. The cranial nerves and spinal cord link
the brain to the peripheral nervous system.

Common symptoms of diffuse autonomic neuropathy include:


impaired urination and sexual function



bladder infections



stomach disorders, due to the impaired ability of the
stomach to empty (gastric stasis)



nausea, vomiting and bloating



dizziness, lightheadedness, and fainting spells



loss of appetite

Diabetes mellitus—Disease characterized by the
inability of the body to produce or respond properly to insulin, required by the body to convert
glucose to energy.
Glucose—The type of sugar found in the blood.
Peripheral nervous system (PNS)—One of the two
major divisions of the nervous system. PNS nerves
link the central nervous system with sensory
organs, muscles, blood vessels, and glands.

Common symptoms of focal neuropathy include:


pain in the front of a thigh



severe pain in the lower back



pain in the chest or stomach



neurologists: specialists in nervous system disorders



ache behind an eye



urologists: specialists in urinary tract disorder



double vision



gastroenterologists: specialists in digestive disorders



paralysis on one side of the face



podiatrists: specialists in caring for the feet

In severe diabetic neuropathy loss of sensation
can lead to injuries that are unnoticed, progressing to
infections, ulceration and possibly amputation.

Diagnosis
The diagnosis of neuropathy is based on the
symptoms that present during a physical exam. Pain
assessment is usually the first step. Patients may have
more than one type of pain, and the history helps the
doctor determine whether a the pain has a neuropathic
cause.
The exam may include:


a screening test for lost sensation



nerve conduction studies to check the flow of electric
current through a nerve



electromyography (EMG) to see how well muscles
respond to electrical impulses transmitted by nearby
nerves.



ultrasound to show how the bladder and other parts
of the urinary tract are functioning



sometimes a nerve biopsy may be performed.

GALE ENCYCLOPEDIA OF MEDICINE

Specialists who treat diabetic neuropathy include:

Treatment
Treatment of diabetic neuropathy is usually
focused on treating the symptoms associated with the
neuropathy and addressing the underlying cause by
improving the control of blood sugar levels, which
may heal the early stages of neuropathy.
There is no cure for the permanent nerve damage
caused by neuropathy. To help control pain, the choice
of proven drug therapies has broadened during the past
decade. Pain medication, such as the topical skin cream
capsaicin, is usually no stronger than codeine because of
the potential for addiction with long-term use of such
drugs. Four main classes of drugs are available for pain
management, alone or in combination: tricyclic antidepressants (Imipramine, Nortriptyline), narcotic analgesics (Morphine), anticonvulsants (Carbamazepine,
Gabapentin), and antiarrhythmics.

Prognosis
Early stage diabetic neuropathy can usually be
reversed with good glucose control. Once nerve
1165

Diabetic neuropathy

Common symptoms of diffuse peripheral neuropathy include:

Dialysis, kidney

damage has occurred it cannot be reversed. The prognosis is largely dependent on the management of the
underlying condition, diabetes, which may halt the
progression of the neuropathy and improve symptoms. Recovery, if it occurs, is slow.

Prevention
Tight glucose control and the avoidance of alcohol and cigarettes help protect nerves from damage.
Resources

Precautions
Blood pressure changes associated with hemodialysis may pose a risk for patients with heart problems.
Peritoneal dialysis may be the preferred treatment
option in these cases.
Peritoneal dialysis is not recommended for patients
with abdominal adhesions or other abdominal defects,
such as a hernia, that might compromise the efficiency
of the treatment. It is also not recommended for
patients who suffer frequent bouts of diverticulitis, an
inflammation of small pouches in the intestinal tract.

ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) DIABETES (800342-2383). <http://www.diabetes.org/>.
Juvenile Diabetes Foundation. 120 Wall St., 19th Floor,
New York, NY 10005. (800) 533-CURE. <http://
www.jdf.org/>.

Gary Gilles

I Dialysis, kidney
Definition
Dialysis treatment replaces the function of the
kidneys, which normally serve as the body’s natural
filtration system. Through the use of a blood filter and
a chemical solution known as dialysate, the treatment
removes waste products and excess fluids from the
bloodstream, while maintaining the proper chemical
balance of the blood. There are two types of dialysis
treatment: hemodialysis and peritoneal dialysis.

Purpose
Dialysis can be used in the treatment of patients
suffering from poisoning or overdose, in order to
quickly remove drugs from the bloodstream. Its most
prevalent application, however, is for patients with
temporary or permanent kidney failure. For patients
with end-stage renal disease (ESRD), whose kidneys
are no longer capable of adequately removing fluids
and wastes from their body or of maintaining the
proper level of certain kidney-regulated chemicals in
the bloodstream, dialysis is the only treatment option
available outside of kidney transplantation. In 1996
in the United States, over 200,000 people underwent
regular dialysis treatments to manage their ESRD.
1166

Description
There are two types of dialysis treatment: hemodialysis and peritoneal dialysis:
Hemodialysis
Hemodialysis is the most frequently prescribed
type of dialysis treatment in the United States. The
treatment involves circulating the patient’s blood outside of the body through an extracorporeal circuit
(ECC), or dialysis circuit. Two needles are inserted
into the patient’s vein, or access site, and are attached
to the ECC, which consists of plastic blood tubing, a
filter known as a dialyzer (artificial kidney), and a
dialysis machine that monitors and maintains blood
flow and administers dialysate. Dialysate is a chemical
bath that is used to draw waste products out of the
blood.
Since the 1980s, the majority of hemodialysis
treatments in the United States have been performed
with hollow fiber dialyzers. A hollow fiber dialyzer is
composed of thousands of tube-like hollow fiber
strands encased in a clear plastic cylinder several
inches in diameter. There are two compartments
within the dialyzer (the blood compartment and the
dialysate compartment). The membrane that separates these two compartments is semipermeable. This
means that it allows the passage of certain sized molecules across it, but prevents the passage of other, larger
molecules. As blood is pushed through the blood compartment in one direction, suction or vacuum pressure
pulls the dialysate through the dialysate compartment
in a countercurrent, or opposite direction. These
opposing pressures work to drain excess fluids out of
the bloodstream and into the dialysate, a process
called ultrafiltration.
A second process called diffusion moves waste
products in the blood across the membrane into the
dialysate compartment, where they are carried out of
the body. At the same time, electrolytes and other
GALE ENCYCLOPEDIA OF MEDICINE

Most hemodialysis patients require treatment
three times a week, for an average of three–four
hours per dialysis ‘‘run.’’ Specific treatment schedules depend on the type of dialyzer used and the
patient’s current physical condition. While the treatment prescription and regimen is usually overseen by
a nephrologist (a doctor that specializes in the kidney), dialysis treatments are typically administered
by a nurse or patient care technician in outpatient
clinics known as dialysis centers, or in hospital-based
dialysis units. In-home hemodialysis treatment is also
an option for some patients, although access to this
type of treatment may be limited by financial and
lifestyle factors. An investment in equipment is
required and another person in the household should
be available for support and assistance with
treatments.
Peritoneal dialysis
In peritoneal dialysis, the patient’s peritoneum, or
lining of the abdomen, acts as a blood filter. A catheter
is surgically inserted into the patient’s abdomen.
During treatment, the catheter is used to fill the
abdominal cavity with dialysate. Waste products and
excess fluids move from the patient’s bloodstream into
the dialysate solution. After a waiting period of six to
24 hours, depending on the treatment method used,
the waste-filled dialysate is drained from the abdomen,
and replaced with clean dialysate.
There are three types of peritoneal dialysis:






Continuous ambulatory peritoneal dialysis
(CAPD). A continuous treatment that is selfadministered and requires no machine. The patient
inserts fresh dialysate solution into the abdominal
cavity, waits four to six hours, and removes the used
solution. The solution is immediately replaced with
fresh dialysate. A bag attached to the catheter is
worn under clothing.
Continuous cyclic peritoneal dialysis (CCPD). An
overnight treatment that uses a machine to drain
and refill the abdominal cavity, CCPD takes 10–12
hours per session.
Intermittent peritoneal dialysis (IPD). This hospitalbased treatment is performed several times a week. A
machine administers and drains the dialysate solution, and sessions can take up to 24 hours.

Peritoneal dialysis is often the treatment option of
choice in infants and children, whose small size can
GALE ENCYCLOPEDIA OF MEDICINE

make vascular (through a vein) access difficult to
maintain. Peritoneal dialysis can also be done outside
of a clinical setting, which is more conducive to regular
school attendance.

Preparation
Patients are weighed immediately before and
after each hemodialysis treatment to assess their
fluid retention. Blood pressure and temperature
are taken and the patient is assessed for physical
changes since their last dialysis run. Regular blood
tests monitor chemical and waste levels in the
blood. Prior to treatment, patients are typically
administered a dose of heparin, an anticoagulant
that prevents blood clotting, to ensure the free flow
of blood through the dialyzer and an uninterrupted
dialysis run for the patient.

Aftercare
Both hemodialysis and peritoneal dialysis patients
need to be vigilant about keeping their access sites and
catheters clean and infection-free during and between
dialysis runs.
Dialysis is just one facet of a comprehensive treatment approach for ESRD. Although dialysis treatment is very effective in removing toxins and fluids
from the body, there are several functions of the kidney it cannot mimic, such as regulating high blood
pressure and red blood cell production. Patients with
ESRD need to watch their diet and fluid intake carefully and take medications as prescribed to manage
their disease.

Risks
Many of the risks and side effects associated with
dialysis are a combined result of both the treatment
and the poor physical condition of the ESRD patient.
Dialysis patients should always report side effects to
their healthcare provider.
Anemia
Hematocrit (Hct) levels, a measure of red blood
cells, are typically low in ESRD patients. This deficiency is caused by a lack of the hormone erythropoietin, which is normally produced by the kidneys. The
problem is elevated in hemodialysis patients, who may
incur blood loss during hemodialysis treatments.
Epoetin alfa, or EPO (sold under the trade name
Epogen), a hormone therapy, and intravenous or
1167

Dialysis, kidney

chemicals in the dialysate solution cross the membrane
into the blood compartment. The purified, chemically
balanced blood is then returned to the body.

Dialysis, kidney

Hemodialyzer (where
filtering takes place)

Hemodialysis machine

Blood flows
to dialyzer

Cleansed blood
flows back to body

Hemodialysis is the most frequently prescribed type of dialysis treatment in the United States. This treatment involves
circulating the patient’s blood outside of the body through a dialysis circuit. The blood is filtered and cleansed inside the
hemodialyzer and returned to the body. (Illustration by Electronic Illustrators Group.)

oral iron supplements are used to manage anemia in
dialysis patients.
Cramps, nausea, vomiting, and headaches
Some hemodialysis patients experience cramps and
flu-like symptoms during treatment. These can be
caused by a number of factors, including the type of
dialysate used, composition of the dialyzer membrane,
water quality in the dialysis unit, and the ultrafiltration
rate of the treatment. Adjustment of the dialysis prescription often helps alleviate many symptoms.
Hypotension
Because of the stress placed on the cardiovascular
system with regular hemodialysis treatments, patients
are at risk for hypotension, a sudden drop in blood
pressure. This can often be controlled by medication
and adjustment of the patient’s dialysis prescription.
1168

Infection
Both hemodialysis and peritoneal dialysis patients
are at risk for infection. Hemodialysis patients should
keep their access sites clean and watch for signs of
redness and warmth that could indicate infection.
Peritoneal dialysis patients must follow the same precautions with their catheter. Peritonitis, an infection of
the peritoneum, causes flu-like symptoms and can
disrupt dialysis treatments if not caught early.
Infectious diseases
Because there is a great deal of blood exposure
involved in dialysis treatment, a slight risk of contracting
hepatitis B and hepatitis C exists. The hepatitis B vaccination is recommended for most hemodialysis patients.
As of 1997, there had only been one documented case of
HIV being transmitted in a United States dialysis unit to
a staff member, and no documented cases of HIV ever
GALE ENCYCLOPEDIA OF MEDICINE

Access site—The vein tapped for vascular access in
hemodialysis treatments. For patients with temporary
treatment needs, access to the bloodstream is gained
by inserting a catheter into the subclavian vein near
the patient’s collarbone. Patients in long-term dialysis require stronger, more durable access sites, called
fistulas or grafts, that are surgically created.
Dialysate—A chemical bath used in dialysis to
draw fluids and toxins out of the bloodstream and
supply electrolytes and other chemicals to the
bloodstream.

ORGANIZATIONS

American Association of Kidney Patients. 100 S. Ashley Dr.,
#280, Tampa, FL 33602. (800) 749-2257. <http://
www.aakp.org>.
American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.
United States Renal Data System (USRDS). The University
of Michigan, 315 W. Huron, Suite 240, Ann Arbor, MI
48103. (734) 998-6611. <http://www.med.umich.edu/
usrds>.

Dialysis prescription—The general parameters of
dialysis treatment that vary according to each
patient’s individual needs. Treatment length, type
of dialyzer and dialysate used, and rate of ultrafiltration are all part of the dialysis prescription.
Dialyzer—An artificial kidney usually composed
of hollow fiber which is used in hemodialysis to
eliminate waste products from the blood and
remove excess fluids from the bloodstream.
Erythropoietin—A hormone produced by the kidneys that stimulates the production of red blood
cells by bone marrow.
ESRD—End-stage renal disease; chronic or permanent kidney failure.
Extracorporeal circuit (ECC)—The path the hemodialysis patient’s blood takes outside of the body. It
typically consists of plastic tubing, a hemodialysis
machine, and a dialyzer.
Hematocrit (Hct) level—A measure of red blood
cells.
Peritoneum—The abdominal cavity; the peritoneum acts as a blood filter in peritoneal dialysis.

being transmitted between dialysis patients in the United
States. The strict standards of infection control practiced
in modern hemodialysis units makes the chance of contracting one of these diseases very small.

Normal results
Puffiness in the patient related to edema, or fluid
retention, may be relieved after dialysis treatment. The
patient’s overall sense of physical well-being may also
be improved. Because dialysis is an ongoing treatment
process for many patients, a baseline for normalcy can
be difficult to gauge.
GALE ENCYCLOPEDIA OF MEDICINE

Paula Anne Ford-Martin

I Diaper rash
Definition
Dermatitis of the buttocks, genitals, lower abdomen, or thigh folds of an infant or toddler is commonly referred to as diaper rash.

Description
The outside layer of skin normally forms a
protective barrier that prevents infection. One of the
primary causes of dermatitis in the diaper area is
prolonged skin contact with wetness. Under these
circumstances, natural oils are stripped away, the
outer layer of skin is damaged, and there is increased
susceptibility to infection by bacteria or yeast.
Diaper rash is a term that covers a broad variety
of skin conditions that occur on the same area of the
body. Some babies are more prone to diaper rash than
others.

Causes and symptoms
Frequently a flat, red rash is caused by simple
chafing of the diaper against tender skin, initiating a
friction rash. This type of rash is not seen in the skin
folds. It may be more pronounced around the edges of
the diaper, at the waist and leg bands. The baby generally doesn’t appear to experience much discomfort.
Sometimes the chemicals or detergents in the diaper
are contributing factors and may result in contact
dermatitis. These rashes should clear up easily with
1169

Diaper rash

Resources

KEY TERMS

Diaper rash

proper attention. Ignoring the condition may lead to a
secondary infection that is more difficult to resolve.
Friction of skin against itself can cause a rash in
the baby’s skin folds, called intertrigo. This rash
appears as reddened areas that may ooze and is often
uncomfortable when the diaper is wet. Intertrigo can
also be found on other areas of the body where there
are deep skin folds that tend to trap moisture.
Seborrheic dermatitis is the diaper area equivalent
of cradle cap. It is scaly and greasy in appearance and
may be worse in the folds of the skin.
Yeast, or candidal dermatitis, is the most common
infectious cause of diaper rash. The affected areas are
raised and quite red with distinct borders, and satellite
lesions may occur around the edges. Yeast is part of
the normal skin flora, and is often an opportunistic
invader when simple diaper rash is untreated. It is
particularly common after treatment with antibiotics,
which kill the good bacteria that normally keep the
yeast population in check. Usual treatments for diaper
rash will not clear it up. Repeated or difficult to
resolve episodes of yeast infection may warrant
further medical attention, since this is sometimes associated with diabetes or immune problems.
Another infectious cause of diaper rash is impetigo. This bacterial infection is characterized by blisters that ooze and crust.

Diagnosis
The presence of skin lesions in the diaper area
means that the baby has diaper rash. However, there
are several types of rash that may require specific
treatment in order to heal. It is useful to be able to
distinguish them by appearance as described above.
A baby with a rash that does not clear up within
two to three days or a rash with blisters or bleeding
should be seen by a healthcare professional for further
evaluation.

Treatment
Antibiotics are generally prescribed for rashes
caused by bacteria, particularly impetigo. This may
be a topical or oral formulation, depending on the
size of the area involved and the severity of the
infection.
Over-the-counter antifungal creams, such as
Lotrimin, are often recommended to treat a rash
resulting from yeast. If topical treatment is not effective, an oral antifungal may be prescribed.
1170

Baby with severe diaper rash. (Custom Medical Stock Photo.
Reproduced by permission.)

Mild steroid creams, such as 0.5–1% hydrocortisone, can be used for seborrheic dermatitis and sometimes intertrigo. Prescription strength creams may be
needed for short-term treatment of more stubborn
cases.

Alternative treatment
Good diaper hygiene will prevent or clear up
many simple cases of diaper rash. Diapers should be
checked very frequently and changed as soon as they
are wet or soiled. Good air circulation is also important for healthy skin. Babies should have some time
without wearing a diaper, and a waterproof pad can be
used to protect the bed or other surface. Rubber pants,
or other occlusive fabrics, should not be used over the
diaper area. Some cloth-like disposable diapers promote better air circulation than plastic-type diapers. It
may be necessary for mothers to experiment with diaper types to see if the baby’s skin reacts better to cloth
or disposable ones. If disposable diapers are used, the
baby’s skin may react differently to various brands. If
the baby is wearing cloth diapers, they should be
washed in a mild detergent and double rinsed.
The diaper area should be cleaned with something
mild, even plain water. Some wipes contain alcohol or
chemicals that can be irritating for some babies. Plain
water may be the best cleansing substance when there
is a rash. Using warm water in a spray bottle (or giving
a quick bath) and then lightly patting the skin dry can
produce less skin trauma than using wipes. In the
event of suspected yeast, a tablespoon of cider vinegar
can be added to a cup of warm water and used as a
cleansing solution. This is dilute enough that it should
not burn, but acidifies the skin pH enough to hamper
the yeast growth.
GALE ENCYCLOPEDIA OF MEDICINE

Dermatitis—Inflammation of the skin.

OTHER

Greene, Alan. ‘‘Diaper Rash.’’ Dr. Greene’s House Calls.
1996. <http://drgreene.com/960430.asp>.

Judith Turner
Barrier ointments can be valuable to treat rashes.
Those that contain zinc oxide are especially effective.
These creams and ointments protect already irritated
skin from the additional insult of urine and stool,
particularly if the baby has diarrhea. Cornstarch powder may be used on rashes that are moist, such as
impetigo.
Nutrition
What the baby eats can make a difference in stool
frequency and acidity. Typically, breast-fed babies will
have fewer problems with rashes. When adding a new
food to the diet, the baby should be observed closely to
see whether rashes are produced around the baby’s
mouth or anus. If this occurs, the new food should
be discontinued.
Babies who are taking antibiotics are more likely
to get rashes due to yeast. To help bring the good
bacterial counts back to normal, Lactobacillus bifidus
can be added to the diet. It is available in powder form
from most health food stores.
Herbal treatment
Some herbal preparations can be useful for diaper
rash. Calendula reduces inflammation, tightens tissues, and disinfects. It has been recommended for
seborrheic dermatitis as well as for general inflammation of the skin. The ointment should be applied at
each diaper change. Chickweed ointment can also be
soothing for irritated skin and may be applied once or
twice daily.

Prognosis
Treated appropriately, diaper rash will resolve
fairly quickly if there is no underlying health problem
or skin disease.

Prevention
Frequent diaper changes are important to keep
the skin dry and healthy. Application of powders
and ointments is not necessary when there is no rash.
Finding the best combination of cleansing and diapering products for the individual baby will also help to
prevent diaper rash.
GALE ENCYCLOPEDIA OF MEDICINE

I Diaphragm (birth control)
Definition
Diaphragms are dome-shaped barrier methods of
contraception that block sperm from entering the
uterus. They are made of latex (rubber) and formed
like a shallow cup. Since vaginas vary in size, each
patient will need to be fitted by a doctor or nurse
with a diaphragm that conforms to the shape and
contour of the vagina as well as the strength of the
muscles in the vaginal walls. Diaphragms must be used
with spermicidal cream or jelly. The device should
cause no discomfort, and neither the woman nor her
partner should feel that it is there.

Purpose
The purpose of a diaphragm is to prevent access to
the womb (uterus) by the sperm and thus prevent
conception. The level of effectiveness is about 95%.

Precautions
Each client will undergo a physical examination
and a Pap smear. If these are normal, the physician
will fit the patient for the device and give instructions
on how to insert, remove, and clean the object. She will
also be taught the signs and symptoms of potential
complications.

Description
Prior to insertion, the inside of the dome and the
rim are covered with a thick layer (perhaps a tablespoon) of a spermicide that is compatible with the
diaphragm being used. The domed area covers the
opening into the uterus (cervix) and keeps the spermicide in place. As a result, any sperm that might get
under the diaphragm will be destroyed.
Diaphragms may be inserted two–three hours prior
to intercourse, and must be left in place for six to eight
hours following sexual relations. During this time the
woman may not swim, bathe, or douche, but she may
1171

Diaphragm (birth control)

Resources

KEY TERMS

Diarrhea

KEY TERMS
Spermicide—A substance that kills sperm.
Toxic shock syndrome—An uncommon, but
potentially fatal, disease that has been associated
with the use of diaphragms and vaginal tampons.
The symptoms include high fever, vomiting, and
diarrhea.

from which the device is made is also possible.
Diaphragm use is also associated with an increased
risk of bladder infections.
It should be noted that the diaphragm can become
dislodged during intercourse, which could result in an
unwanted pregnancy. To ensure a secure fit, a woman
should be examined for a refitting if she gains or loses
more than 10 lbs (4.5 kg), or after she gives birth.

Normal results
shower. If she desires to have intercourse again before
the six to eight hours have passed, the diaphragm
should not be removed. Instead, an applicator full of
spermicide should be deposited into the vagina.

Consumers can expect an efficiency rate of about
95% in preventing pregnancy. Using a male condom in
conjunction with the diaphragm decreases the potential for pregnancy. Diaphragms provide no protection
against AIDS or other sexually transmitted diseases.

A diaphragm will last for a year or more. It should
be examined weekly for holes. This can be done by
holding it up to the light or filling it with water.

Resources

Preparation
Before inserting the diaphragm, the woman
should empty her bladder and wash her hands with
soap and water. The device should be checked for
leaks by filling it with water or holding it up to the
light. A spermicidal jelly is then applied to the inside
and outside, and especially around the rim. While
standing with one foot elevated on a chair or step,
lying down, or squatting, the woman folds the diaphragm inward toward the middle and inserts it into
the vagina as far as it will go.

ORGANIZATIONS

Planned Parenthood Federation of America, Inc. 810
Seventh Ave., New York, NY, 10019. (800) 669-0156.
<http://www.plannedparenthood.org>.
OTHER

‘‘The Diaphragm.’’ Cincinnati Women’s Services. <http://
gynpages.com/cws/8.html>.
‘‘Guide to Safer Sex.’’ Sexual Health InfoCenter. <http://
www.sexhealth.org/infocenter/GuideSS/
diaphragm.htm>.

Donald G. Barstow, RN

Diaphragmatic hernia see Hernia

Aftercare
When removed, the diaphragm should be washed
with a mild soap and water. After being dried, it can be
dusted with corn starch before being returned to its
container. The diaphragm should always be stored
away from sunlight and heat in a cool, dry place. It
should not be washed with harsh or perfumed soaps or
used with perfumed powders because either of these
substances can damage the diaphragm.

Risks
Although rare, wearing the diaphragm longer
than the recommended time can result in toxic shock
syndrome. The signs and symptoms of this serious
illness include sudden onset of high fever, vomiting,
diarrhea, dizziness, faintness, weakness, aching muscles and joints, and rash. The doctor must be notified
immediately if any of these conditions appear. An
allergic reaction to the spermicide or the material
1172

I Diarrhea
Definition
To most individuals, diarrhea means an increased
frequency or decreased consistency of bowel movements; however, the medical definition is more exact
than this. In many developed countries, the average
number of bowel movements is three per day.
However, researchers have found that diarrhea best
correlates with an increase in stool weight; stool
weights above 10oz (300 gs) per day generally indicates
diarrhea. This is mainly due to excess water, which
normally makes up 60–85% of fecal matter. In this
way, true diarrhea is distinguished from diseases that
cause only an increase in the number of bowel movements (hyperdefecation) or incontinence (involuntary
loss of bowel contents).
GALE ENCYCLOPEDIA OF MEDICINE

Description
In many cases, acute infectious diarrhea is a mild,
limited annoyance. However, worldwide acute infectious diarrhea has a huge impact, causing over five
million deaths per year. While most deaths are
among children under five years of age in developing
nations, the impact, even in developed countries, is
considerable. For example, over 250,000 individuals
are admitted to hospitals in the United States each
year because of one of these episodes. Rapid diagnosis
and proper treatment can prevent much of the suffering associated with these devastating illnesses.
Chronic diarrhea also has a considerable effect on
health, as well as on social and economic well being.
Patients with celiac disease, inflammatory bowel disease, and other prolonged diarrheal illnesses develop
nutritional deficiencies that diminish growth and
immunity. They affect social interaction and result in
the loss of many working hours.

Causes and symptoms
Diarrhea occurs because more fluid passes
through the large intestine (colon) than that organ
can absorb. As a rule, the colon can absorb several
times more fluid than is required on a daily basis.
However, when this reserve capacity is overwhelmed,
diarrhea occurs.
Diarrhea is caused by infections or illnesses that
either lead to excess production of fluids or prevent
absorption of fluids. Also, certain substances in the
colon, such as fats and bile acids, can interfere with
water absorption and cause diarrhea. In addition,
rapid passage of material through the colon can also
do the same.
Symptoms related to any diarrheal illness are
often those associated with any injury to the gastrointestinal tract, such as fever, nausea, vomiting, and
abdominal pain. All or none of these may be present
depending on the disease causing the diarrhea. The
number of bowel movements can vary—up to 20 or
more per day. In some patients, blood or pus is present
in the stool. Bowel movements may be difficult to
flush (float) or contain undigested food material.
The most common causes of acute diarrhea are
infections (the cause of traveler’s diarrhea), food
GALE ENCYCLOPEDIA OF MEDICINE

poisoning, and medications. Medications are a frequent and often over-looked cause, especially antibiotics and antacids. Less often, various sugar free foods,
which sometimes contain poorly absorbable materials,
cause diarrhea.
Chronic diarrhea is frequently due to many of the
same things that cause the shorter episodes (infections,
medications, etc.); symptoms just last longer. Some
infections can become chronic. This occurs mainly
with parasitic infections (such as Giardia) or when
patients have altered immunity (AIDS).
The following are the more usual causes of
chronic diarrhea:


AIDS



colon cancer and other bowel tumors



endocrine or hormonal abnormalities (thyroid, diabetes mellitus, etc.)



food allergy



inflammatory bowel disease (Crohn’s disease and
ulcerative colitis)



lactose intolerance



malabsorption syndromes (celiac and Whipple’s
disease)



other (alcohol,
surgery)

microscopic

colitis,

radiation,

Complications
The major effects of diarrhea are dehydration,
malnutrition, and weight loss. Signs of dehydration
can be hard to notice, but increasing thirst, dry
mouth, weakness or lightheadedness (particularly if
worsening on standing), or a darkening/decrease in
urination are suggestive. Severe dehydration leads to
changes in the body’s chemistry and could become lifethreatening. Dehydration from diarrhea can result in
kidney failure, neurological symptoms, arthritis, and
skin problems.

Diagnosis
Most cases of acute diarrhea never need diagnosis
or treatment, as many are mild and produce few problems. But patients with fever over 102 8F (38.9 8C),
signs of dehydration, bloody bowel movements, severe
abdominal pain, known immune disease, or prior use
of antibiotics need prompt medical evaluation.
When diagnostic studies are needed, the most useful are stool culture and examination for parasites;
however these are often negative and a cause cannot
be found in a large number of patients. The earlier
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Diarrhea

Diarrhea is also classified by physicians into
acute, which lasts one or two weeks, and chronic,
which continues for longer than 2 or 3 weeks. Viral
and bacterial infections are the most common causes
of acute diarrhea.

Diarrhea

cultures are performed, the greater the chance of
obtaining a positive result. For those with a history
of antibiotic use in the preceding two months, stool
samples need to be examined for the toxins that cause
antibiotic-associated colitis. Tests are also available to
check stool samples for microscopic amounts of blood
and for cells that indicate severe inflammation of the
colon. Examination with an endoscope is sometimes
helpful in determining severity and extent of inflammation. Tests to check changes in blood chemistry
(potassium, magnesium, etc.) and a complete blood
count (CBC) are also often performed.
Chronic diarrhea is quite different, and most
patients with this condition will receive some degree of
testing. Many exams are the same as for an acute
episode, as some infections and parasites cause both
types of diarrhea. A careful history to evaluate medication use, dietary changes, family history of illnesses, and
other symptoms is necessary. Key points in determining
the seriousness of symptoms are weight loss of over
10 lb (4.5 kg), blood in the stool, and nocturnal diarrhea
(symptoms that awaken the patient from sleep).
Both prescription and over-the-counter medications can contain additives, such as lactose and sorbitol, that will produce diarrhea in sensitive individuals.
Review of allergies or skin changes may also point to a
cause. Social history may indicate if stress is playing a
role or identify activities which can be associated with
diarrhea (for example, diarrhea that occurs in
runners).
A combination of stool, blood, and urine tests
may be needed in the evaluation of chronic diarrhea;
in addition a number of endoscopic and x-ray studies
are frequently required.

Treatment
Treatment is ideally directed toward correcting
the cause; however, the first aim should be to prevent
or treat dehydration and nutritional deficiencies. The
type of fluid and nutrient replacement will depend on
whether oral feedings can be taken and the severity of
fluid losses. Oral rehydration solution (ORS) or intravenous fluids are the choices; ORS is preferred if
possible.
A physician should be notified if the patient is
dehydrated, and if oral replacement is suggested then
commercial (Pedialyte and others) or homemade
preparations can be used. The World Health
Organization (WHO) has provided this easy recipe
for home preparation, which can be taken in small
frequent sips:
1174



Table salt—3/4 tsp



Baking powder—1 tsp



Orange juice—1 c



Water—1 qt (1l)

When feasible, food intake should be continued
even in those with acute diarrhea. A physician should
be consulted as to what type and how much food is
permitted.
Anti-motility agents (loperamide, diphenoxylate)
are useful for those with chronic symptoms; their use is
limited or even contraindicated in most individuals
with acute diarrhea, especially in those with high
fever or bloody bowel movements. They should not
be taken without the advice of a physician.
Other treatments are available, depending on the
cause of symptoms. For example, the bulk agent psyllium helps some patients by absorbing excess fluid
and solidifying stools; cholestyramine, which binds
bile acids, is effective in treating bile salt induced
diarrhea. Low fat diets or more easily digestible fat is
useful in some patients. New antidiarrheal drugs that
decrease excessive secretion of fluid by the intestinal
tract is another approach for some diseases.
Avoidance of medications or other products that are
known to cause diarrhea (such as lactose) is curative in
some, but should be discussed with a physician.

Alternative treatment
It is especially important to find the cause of
diarrhea, since stopping diarrhea when it is the
body’s way of eliminating something foreign is not
helpful and can be harmful in the long run.
One effective alternative approach to preventing
and treating diarrhea involves oral supplementation of
aspects of the normal flora in the colon with the yeasts
Lactobacillus acidophilus, L. bifidus, or Saccharomyces
boulardii. In clinical settings, these ‘‘biotherapeutic’’
agents have repeatedly been helpful in the resolution
of diarrhea, especially antibiotic-associated diarrhea.
Their effectiveness is also supported by the results of a
research study published in the Journal of the
American Medical Association in 1996.
Nutrient replacement also plays a role in preventing and treating episodes of diarrhea. Zinc especially
appears to have an effect on the immune system, and
deficiency of this mineral can lead to chronic diarrhea.
Also, zinc replacement improves growth in young
patients. Plenty of fluids, especially water, should be
taken by individuals suffering from diarrhea to prevent dehydration. The BRAT diet also can be useful in
GALE ENCYCLOPEDIA OF MEDICINE

Anti-motiltiy medications—Medications such as
loperamide (Imodium), diphenoxylate (Lomotil),
or medications containing codeine or narcotics
that decrease the ability of the intestine to contract.
These can worsen the condition of a patient with
dysentery or colitis.
Colitis—Inflammation of the colon.
Endoscope—An endoscope, as used in the field of
gastroenterology, is a thin flexible tube that uses a
lens or miniature camera to view various areas of
the gastrointestinal tract. Both diagnosis, through
biopsies or other means, and therapeutic procedures can be done with this instrument.
Endoscopy—The performance of an exam using an
endoscope is known generally as endoscopy.
Lactose intolerance—An inability to properly
digest milk and dairy products.
Oral rehydration solution (ORS)—A liquid preparation developed by the World Health Organization that can decrease fluid loss in persons with
diarrhea. Originally developed to be prepared with
materials available in the home, commercial preparations have recently come into use.
Steatorrhea—Excessive amounts of fat in the feces.

Proper hygiene and food handling techniques will
prevent many cases. Traveler’s diarrhea can be
avoided by use of Pepto-Bismol and/or antibiotics, if
necessary. The most important action is to prevent the
complications of dehydration.
Resources
ORGANIZATIONS

World Health Organization, Division of Emerging and Other
Communicable Diseases Surveillance and Control.
Avenue Appia 20, 1211 Geneva 27, Switzerland. (+00 41
22) 791 21 11.<http://www.who.int>.
OTHER

‘‘Directory of Digestive Diseases Organizations for
Patients.’’ National Institute of Diabetes and Digestive
and Kidney Disease. <http://www.niddk.nih.gov>.
‘‘A Neglected Modality for the Treatment and Prevention of
Selected Intestinal and Vaginal Infections.’’ JAMA.
<http://pubs.ama-assn.org>.
Selected publications and documents on diarrhoeal diseases
(including cholera). World Health Organization
(WHO). <http://www.who.ch/chd/pub/cdd/
cddpub.htm>.

David Kaminstein, MD

Diazep see Benzodiazepines
Diclofenac see Nonsteroidal antiinflammatory drugs

helping to resolve diarrhea. This diet limits food intake
to bananas, rice, applesauce, and toast. These foods
provide soluble and insoluble fiber without irritation.
If the toast is slightly burnt, the charcoal can help
sequester toxins and pull them from the body.
Acute homeopathic remedies can be very effective
for treating diarrhea especially in infants and young
children.

Dicyclomine see Antispasmodic drugs
Didanosine see Antiretroviral drugs

I Diets
Definition

Prognosis
Prognosis is related to the cause of the diarrhea;
for most individuals in developed countries, a bout of
acute, infectious diarrhea is at best uncomfortable.
However, in both industrialized and developing
areas, serious complications and death can occur.
For those with chronic symptoms, an extensive
number of tests are usually necessary to make a proper
diagnosis and begin treatment; a specific diagnosis is
found in 90% of patients. In some, however, no specific cause is found and only treatment with bulk
agents or anti-motility agents is indicated.
GALE ENCYCLOPEDIA OF MEDICINE

Humans may alter their usual eating habits for
many reasons, including weight loss, disease prevention or treatment, removing toxins from the body, or
to achieve a general improvement in physical and
mental health. Others adopt special diets for religious
reasons. In the case of some vegetarians and vegans,
dietary changes are made out of ethical concerns for
the rights of animals.

Purpose
People who are moderately to severely overweight
can derive substantial health benefits from a
1175

Diets

Prevention

KEY TERMS

Diets

weight-loss diet. A weight reduction of just 10–20
pounds can result in reduced cholesterol levels and
lower blood pressure. Weight-related health problems
include heart disease, diabetes, high blood pressure,
and high levels of blood sugar and cholesterol.
In individuals who are not overweight, dietary
changes also may be useful in the prevention or treatment of a range of ailments including acquired
immuno deficiency syndrome (AIDS), cancer, osteoporosis, inflammatory bowel disease, chronic pulmonary disease, renal disease, Parkinson’s disease, seizure
disorders, and food allergies and intolerances.

Description
Origins
The practice of altering diet for special reasons has
existed since antiquity. For example, Judaism has
included numerous dietary restrictions for thousands
of years. One ancient Jewish sect, the Essenes, is said
to have developed a primitive detoxification diet aimed
at preparing the bodies, minds, and spirits of its members for the coming of a ‘‘messiah’’ who would deliver
them from their Roman captors. Preventive and therapeutic diets became popular during the late twentieth
century. Books promoting the latest dietary plan continue to make the bestseller lists, although not all of
the information given is considered authoritative.
The idea of a healthful diet is to provide all of the
calories and nutrients needed by the body for optimal
performance, at the same time ensuring that neither
nutritional deficiencies nor excesses occur. Diet plans
that claim to accomplish those objectives are so
numerous they are virtually uncountable. These diets
employ a variety of approaches, including the
following:


Fixed-menu: Offers little choice to the dieter.
Specifies exactly which foods will be consumed.
Easy to follow, but may be considered boring to
some dieters.

diet is a stricter form of vegetarianism in which eggs,
cheese, and other milk products are prohibited.
A third way of classifying diets is according to
their purpose: religious, weight-loss, detoxification,
lifestyle-related, or aimed at prevention or treatment
of a specific disease.

Precautions
Dieters should be cautious about plans that
severely restrict the size of food portions, or that eliminate entire food groups from the diet. It is highly
probable that they will become discouraged and drop
out of such programs. The best diet is one that can be
maintained indefinitely without ill effects, that offers
sufficient variety and balance to provide everything
needed for good health, and that is considerate of
personal food preferences. Many controversies have
arisen in the past over the benefits and risks of highprotein, low carbohydrate diets such as the Atkins diet.
Most physician groups and health organizations have
spoken out negatively against the program. In 2003,
these statements were largely supported. Though clinical trials showed that these types of diets worked in
lowering weight without raising cholesterol for the
short-term, many of the participants gained a percentage of the weight back after only one year. A physician group also spoke out about high protein
diets’ dangers for people with decreased kidney function and the risk of bone loss due to decreased calcium
intake.
Low-fat diets are not recommended for children
under the age of two. Young children need extra fat to
maintain their active, growing bodies. Fat intake may be
gradually reduced between the ages of two and five, after
which it should be limited to a maximum of 30% of total
calories through adulthood. Saturated fat should be
restricted to no more than 10% of total calories.



Formula: Replaces some or all meals with a nutritionally balanced liquid formula or powder.



Exchange-type: Allows the dieter to choose between
selected foods from each food group.



Flexible: Doesn’t concern itself with the overall diet,
simply with one aspect such as fat or energy.

Weight-loss dieters should be wary of the ‘‘yo-yo’’
effect that occurs when numerous attempts are made
to reduce weight using high-risk, quick-fix diets. This
continued ‘‘cycling’’ between weight loss and weight
gain can slow the basal metabolic rate and can sometimes lead to eating disorders. The dieter may become
discouraged and frustrated by this success/failure
cycle. The end result of yo-yo dieting is that it becomes
more difficult to maintain a healthy weight.

Diets also may be classified according to the types
of foods they allow. For example, an omnivorous diet
consists of both animal and plant foods, whereas a
lacto-ovo-vegetarian diet permits no animal flesh,
but includes eggs, milk, and dairy products. A vegan

Caution also should be exercised about weight
loss diets that require continued purchases of special
prepackaged foods. Not only do these tend to be costly
and over-processed, they also may prevent dieters
from learning the food-selection and preparation skills

1176

GALE ENCYCLOPEDIA OF MEDICINE

Diets

Fats, oils, sweets
(use sparingly)

Milk, yogurt, cheese
(2–3 servings
per day)

Meat, poultry, fish,
eggs, beans, nuts
(2–3) servings per day)

MILK

Vegetables
(3–5 servings
per day)

Fruits
(2–4 servings
per day)

Ce

rea

l

Bre

ad

Bread, rice, cereal, pasta
(6–11 servings per day)

Suggested daily food servings appeared in the food pyramid up until 2005 when it was revised. The current food pyramid does
not contain recommended portions. (Illustration by Electronic Illustrators Group.)

essential to maintenance of weight loss. Further, dieters
should consider whether they want to carry these special foods to work, restaurants, or homes of friends.

weight control over the long term through healthy
lifestyle changes such as eating smaller, more balanced
meals and exercising regularly.

Concern has been expressed about weight-loss
diet plans that do not include exercise, considered
essential to long-term weight management. Some
diets and supplements may be inadvisable for patients
with special conditions or situations. In fact, use of the
weight loss supplement ephedra was found to cause
serious conditions such as heart attack and stroke. In
2003, the U.S. Food and Drug Administration (FDA)
was considering controlling or banning the supplement. In short, most physician organizations see fad
diets as distracting from learning how to achieve

Certain fad diets purporting to be official diets of
groups such as the American Heart Association and the
Mayo Clinic are in no way endorsed by those institutions. People thinking of starting such a diet should
check with the institution to ensure its name has not
been misappropriated by an unscrupulous practitioner.

GALE ENCYCLOPEDIA OF MEDICINE

Side effects
A wide range of side effects (some quite serious)
can result from special diets, especially those that are
1177

Diffuse esophageal spasm

nutritionally unbalanced. Further problems can arise
if the dieter is taking high doses of dietary supplements. Food is essential to life, and improper nutrition
can result in serious illness or death.

Research and general acceptance
It is agreed among traditional and complementary
practitioners that many patients could substantially
benefit from improved eating habits. Specialized
diets have proved effective against a wide variety of
conditions and diseases. However, dozens of
unproved but widely publicized fad diets emerge each
year, prompting widespread concerns about their usefulness, cost to the consumer, and their safety.
Resources
PERIODICALS

‘‘American College of Preventive Medicine Weighs in
Against Fad Diets.’’Obesity and Diabetes Week,
March 17, 2003: 7.
‘‘Atkins Diet Vindicated But Long-term Success
Questionable.’’ Obesity, Fitness and Wellness Week,
June 14, 2003: 25.
‘‘High-protein Diets Risky for Bones and Kidneys.’’ Health
Science, Spring 2003: 9.
Kirn, Timothy F. ‘‘FDA Probes Ephedra, Proposes
Warning Label (Risk of Heart Attack, Seizure,
Stroke).’’ Clinical Psychiatry News, April 2003: 49.
ORGANIZATIONS

American Dietetic Association. 216 West Jackson Blvd.,
Chicago, IL 60606-6995. (312) 899-0040. <http://
www.eatright.org>.

David Helwig
Teresa G. Odle

I Diffuse esophageal spasm
Definition
Diffuse esophageal spasm is a term used to define
an uncoordinated or spastic esophagus.

Description
The esophagus is a muscular tube that actively
transports food from the throat to the stomach by
rhythmic contractions known as peristalsis. The actual
mechanism and anatomy are quite complex, involving
three distinct segments and allowing a person to swallow even when upside-down. Diffuse esophageal
1178

KEY TERMS
Contrast agent—A substance that produces shadows on x rays.
Manometry—Measurement of pressure.
Peristalsis—Slow, rhythmic contractions of the
muscles in a tubular organ, such as the intestines,
that propel the contents along.

spasm describes a condition where the entire esophagus is spastic—along its entire length, the muscular
activity is increased and uncoordinated. The name
corkscrew esophagus describes perfectly the appearance of this disorder on x rays.
X rays may reveal a slightly different appearance
and result in the designation rosary bead esophagus,
but the cause is still diffuse spasm, and the two entities
behave in the same way.

Causes and symptoms
The cause appears to be disruption of the complex
system of nerves that coordinates the muscular activity. The result is difficulty swallowing (dysphagia) and
pain that feels like a heart attack and can involve the
entire chest, jaw, and arms.

Diagnosis
Swallowing problems usually call for esophagograms. In the x-ray department, the patient is given a
contrast agent to drink. During swallowing, x rays
record the passage of the agent down the esophagus
and into the stomach. Instead of a straight tube with
well-coordinated waves of contraction, the resulting x
rays show a writhing organ resembling a giant
corkscrew.
Another test that is used in many disorders of
esophageal motility is manometry. Pressures inside
the esophagus are measured every inch or so using a
balloon device that is passed all the way down to the
stomach. The result is a precise record of its activity
that yields a specific diagnosis.

Treatment
Soft and liquid foods pass more easily than solid
pieces. Medications of several types are helpful—
nifedipine, hydralazine, isoproterenol, and nitrates
being the most successful. Several other treatments
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
This condition does not go away, nor is treatment
entirely satisfactory. Patients need to be careful of
what they eat and continue on medication if a beneficial one is found. Fortunately, the condition does not
get progressively worse as time passes.
Resources
BOOKS

Goyal, Raj K. ‘‘Diseases of the Esophagus.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony
S. Fauci, et al. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

I DiGeorge syndrome
Definition
DiGeorge syndrome (also called 22q11 deletion
syndrome, congenital thymic hypoplasia, or third
and fourth pharyngeal pouch syndrome) is a birth
defect that is caused by an abnormality in chromosome 22 and affects the baby’s immune system. The
disorder is marked by absence or underdevelopment
of the thymus and parathyroid glands. It is named for
Angelo DiGeorge, the pediatrician who first described
it in 1965. Some researchers prefer to call it DiGeorge
anomaly, or DGA, rather than DiGeorge syndrome,
on the grounds that the defects associated with the
disorder represent the failure of a part of the human
embryo to develop normally rather than a collection
of symptoms caused by a single disease.

Description
The prevalence of DiGeorge syndrome is debated;
the estimates range from 1:4000 to 1:6395. Because the
symptoms caused by the chromosomal abnormality
vary somewhat from patient to patient, the syndrome
probably occurs much more often than was previously
thought. DiGeorge syndrome is sometimes described
as one of the ‘‘CATCH 22’’ disorders, so named
because of their characteristics—cardiac defects,
abnormal facial features, thymus underdevelopment,
GALE ENCYCLOPEDIA OF MEDICINE

cleft palate, and hypocalcemia—caused by a deletion
of several genes in chromosome 22. The specific facial
features associated with DiGeorge syndrome include
low-set ears, wide-set eyes, a small jaw, and a short
groove in the upper lip. The male/female ratio is 1:1.
The syndrome appears to be equally common in all
racial and ethnic groups.

Causes and symptoms
DiGeorge syndrome is caused either by inheritance of a defective chromosome 22 or by a new defect
in chromosome 22 in the fetus. The type of defect that
is involved is called deletion. A deletion occurs when
the genetic material in the chromosomes does not
recombine properly during the formation of sperm or
egg cells. The deletion means that several genes from
chromosome 22 are missing in DiGeorge syndrome
patients. Although efforts have been made in the
early 2000s to identify individual candidate genes for
DGA, it appears that a combination of several genes in
the deleted area is responsible for the disorder. Detailed
genetic mapping of chromosome 22 has, however, identified a so-called DiGeorge critical region (DGCR),
which has been completely sequenced.
According to a 1999 study, 6% of children with
DiGeorge syndrome inherited the deletion from a
parent, while 94% had a new deletion. Other conditions that are associated with DiGeorge syndrome are
diabetes (a condition where the pancreas no longer
produces enough insulin) in the mother and fetal alcohol syndrome (a pattern of birth defects, and learning
and behavioral problems affecting individuals whose
mothers consumed alcohol during pregnancy). Other
chromosomal abnormalities that have been found in
patients diagnosed with DGA include deletions on
chromosomes 10p13, 17p13, and 18q21.
The loss of the genes in the deleted material means
that the baby’s third and fourth pharyngeal pouches
fail to develop normally during the twelfth week of
pregnancy. This developmental failure results in a
completely or partially absent thymus gland and parathyroid glands. In addition, 74% of fetuses with
DiGeorge syndrome have severe heart defects. The
child is born with a defective immune system and an
abnormally low level of calcium in the blood. Some
children with DGA are also born with malformations
of the genitals or urinary tract.
These defects usually become apparent within
48 hours of birth. The infant’s heart defects may lead
to heart failure, or there may be seizures and other
evidence of a low level of calcium in the blood
(hypocalcemia).
1179

DiGeorge syndrome

have uncertain results. For severe cases, relief is
obtained two-thirds of the time by cutting the muscles
along the entire length of the esophagus. This is a
major surgical procedure.

DiGeorge syndrome

DiGeorge syndrome is also associated with an
increased risk of autoimmune disorders. Cases have
been reported of DGA in association with Graves’
disease, immune thrombocytopenic purpura, juvenile
rheumatoid arthritis, and severe eczema.

Diagnosis
Diagnosis of DiGeorge syndrome can be made by
ultrasound examination around the eighteenth week
of pregnancy, when abnormalities in the development
of the heart or the palate can be detected. Another
technique that is used to diagnose the syndrome before
birth is called fluorescence in situ hybridization, or
FISH. This technique uses DNA probes from the
DiGeorge region on chromosome 22. FISH can be
performed on cell samples obtained by amniocentesis
as early as the fourteenth week of pregnancy. It confirms about 95% of cases of DiGeorge syndrome.
If the mother has not had prenatal testing, the
diagnosis of DiGeorge syndrome is sometimes suggested by the child’s facial features at birth. In other
cases, the doctor makes the diagnosis during heart
surgery when he or she notices the absence or abnormal location of the thymus gland. The diagnosis can
be confirmed by blood tests for calcium, phosphorus,
and parathyroid hormone levels, and by the sheep cell
test for immune function.

Treatment
Hypocalcemia
Hypocalcemia in DiGeorge patients is unusually
difficult to treat. Infants are usually given calcium and
vitamin D by mouth. Severe cases have been treated by
transplantation of fetal thymus tissue or bone marrow.
Heart defects
Infants with life-threatening heart defects are treated surgically.
Defective immune function
Children with DiGeorge syndrome should be kept
on low-phosphorus diets and kept away from crowds
or other sources of infection. They should not be
immunized with vaccines made from live viruses or
given corticosteroids.

Prognosis
The prognosis is variable; many infants with
DiGeorge syndrome die from overwhelming infection,
1180

KEY TERMS
Deletion—A genetic abnormality in which a segment of a chromosome is lost. DiGeorge syndrome
is caused by a deletion on human chromosome 22.
Fetal alcohol syndrome—A cluster of birth defects
that includes abnormal facial features and mental
retardation, caused by the mother’s consumption of
alcoholic beverages during pregnancy.
Fluorescence in situ hybridization (FISH)—A technique for diagnosing DiGeorge syndrome before
birth by analyzing cells obtained by amniocentesis
with DNA probes. FISH is about 95% accurate.
Hypocalcemia—An abnormally low level of calcium in the blood.
Hypoplasia—A deficiency or underdevelopment of
a tissue or body structure.
T cells—A type of white blood cell produced in the
thymus gland. T cells are an important part of the
immune system. Infants born with an underdeveloped or absent thymus do not have a normal level
of T cells in their blood.

seizures, or heart failure within the first year. One
study of a series of 558 patients reported 8% mortality
within six months of birth, with heart defects accounting for all but one of the deaths. Infections resulting
from severe immune deficiency are the second most
common cause of death in patients with DGA.
Advances in heart surgery indicate that the prognosis
is most closely linked to the severity of the heart
defects and the partial presence of the thymus gland.
In most children who survive, the number of T cells, a
type of white blood cell, in the blood rises spontaneously as they mature. Survivors are likely to be
mentally retarded, however, and to have other developmental difficulties, including seizures or other psychiatric and neurological problems in later life.

Prevention
Genetic counseling is recommended for parents of
children with DiGeorge syndrome because the disorder
can be detected prior to birth. Although most children
with DiGeorge syndrome did not inherit the chromosome deletion from their parents, they have a 50%
chance of passing the deletion on to their own children.
Because of the association between DiGeorge syndrome and fetal alcohol syndrome, pregnant women
should avoid drinking alcoholic beverages.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Immunodeficiency Diseases.’’ Section 12, Chapter 147
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
McDonald-McGinn, Donna M., et al. 22q11 Deletion
Syndrome. Philadelphia: The Children’s Hospital of
Philadelphia, 1999.
PERIODICALS

Guduri, Sridhar, MD, and Iftikhar Hussain, MD.
‘‘DiGeorge Syndrome.’’ eMedicine May 28, 2002.
<http://www.emedicine.com/med/topic567.htm>.
Verri, A., P. Maraschio, K. Devriendt, et al. ‘‘Chromosome
10p Deletion in a Patient with Hypoparathyroidism,
Severe Mental Retardation, Autism and Basal Ganglia
Calcifications.’’ Annales de génétique 47
(July-September 2004): 281–287.
Yatsenko, S. A., A. N. Yatsenko, K. Szigeti, et al.
‘‘Interstitial Deletion of 10p and Atrial Septal Defect in
DiGeorge 2 Syndrome.’’ Clinical Genetics 66 (August
2004): 128–136.
ORGANIZATIONS

Canadian 22q Group. 320 Cote Street Antoine, West
Montreal, Quebec H3Y 2J4.
Chromosome Deletion Outreach, Inc. P.O. Box 724, Boca
Raton, FL 33429-0724. (888) 236-6680.
International DiGeorge/VCF Support Network, c/o Family
Voices of New York. 46 1/2 Clinton Avenue, Cortland,
NY 13045. (607) 753-1250.
National Organization for Rare Disorders (NORD).
55 Kenosia Avenue, P. O. Box 1968, Danbury, CT
06813-1968. (203) 744-0100. Fax: (203) 798-2291.
<http://www.rarediseases.org>.

Rebecca J. Frey, PhD

Digital rectal examination see Rectal
examination

I Digitalis drugs
Definition
Digitalis drugs are medicines made from a type of
foxglove plant (Digitalis purpurea) that have a stimulating effect on the heart.

Purpose
Digitalis drugs are used to treat heart problems
such as congestive heart failure and irregular heartbeat.
GALE ENCYCLOPEDIA OF MEDICINE

These medicines help make the heart stronger and more
efficient. This, in turn, improves blood circulation and
helps relieve the swelling of the hands and ankles that is
common in people with heart problems.

Description
Digitalis drugs, also known as digitalis glycosides,
are available only with a physician’s prescription.
They are sold in tablet, capsule, liquid, and injectable
forms. Commonly used digitalis drugs are digitoxin
(Crystodigin) and digoxin (Lanoxin).

Recommended dosage
The recommended dosage is different for each
patient. The physician who prescribes the medicine
will determine the correct dose. Taking exactly the
right amount of medicine and taking it exactly as
directed are very important. Never take larger or
more frequent doses. During treatment with a digitalis
heart medicine, the physician will monitor blood levels
of the drug and will decide whether the dose needs to
be changed. Patients should never change the dose of
this medicine unless told to do so by their physicians.

Precautions
Seeing a physician regularly while taking digitalis
drugs is very important. The physician will check to
make sure the medicine is working as it should and will
make any necessary changes in dosage or in instructions for taking the medicine.
Patients taking digitalis drugs should learn to take
their pulse and should check it regularly while under
treatment with this medicine. Changes in pulse rate,
rhythm, or force could be signs of side effects.
Do not stop taking this medicine suddenly without checking with the physician who prescribed it.
This could cause a serious change in heart function.
Digitalis drugs are responsible for many accidental poisonings in children. Keep this medicine out of
the reach of children.
Be alert to the signs of overdose. Overdosing is a
serious concern with digitalis drugs, because the
amount of medicine that most people need to help
their heart problems is very close to the amount that
can cause problems from overdose. If any of these
signs of overdose occur, check with a physician as
soon as possible:


loss of appetite



nausea
1181

Digitalis drugs

Resources

Digitalis drugs



vomiting



pain in the lower stomach



diarrhea



extreme tiredness or weakness



extremely slow or irregular heartbeat (or fast heartbeat in children)



blurred vision or other vision changes



drowsiness



confusion or depression



headache



fainting

Anyone who is taking digitalis drugs should be
sure to tell the health care professional in charge
before having any surgical or dental procedures or
receiving emergency treatment. Physicians may advise
people taking digitalis drugs to wear or carry medical
identification indicating that they are taking this
medicine.
Patients need to be very careful not to accidentally take this medicine in place of another medicine
that looks similar. Patients who are taking other
medicines that look like their digitalis medicine
should ask their pharmacists for suggestions on how
to avoid mix-ups.
Anyone who has had unusual reactions to digitalis
drugs in the past should let his or her physician know
before taking the drugs again. The physician should
also be told about any allergies to foods, dyes, preservatives, or other substances.
Women who are pregnant or breastfeeding or who
may become pregnant should check with their physicians before using digitalis drugs.
Older people may be especially sensitive to the
effects of digitalis drugs, which may increase the
chance of overdose.
Before using digitalis drugs, people with any of the
following the medical problems should make sure
their physicians are aware of their conditions:


heart disease



heart rhythm problems



severe lung disease



kidney disease



liver disease



thyroid disease

1182

Digitalis purpurea. (Photo Researchers, Inc. Reproduced by
permission.)

Side effects
Side effects are rare with this medicine. Check
with a physician as soon as possible if a skin rash,
hives, or any other unusual or troublesome symptoms
occur. Watch for signs of overdose.

Interactions
Digitalis drugs may interact with a number of
other medicines. When this happens, the effects of
one or both of the drugs may change or the risk
of side effects may be greater. For example:


Taking digitalis drugs with other heart medicines,
amphetamines, or diet pills could increase the risk
of heart rhythm problems.



Calcium channel blockers, used to treat high blood
pressure, may cause higher than usual levels of digitalis drugs in the body that could lead to symptoms
of overdose as covered in the above section.
GALE ENCYCLOPEDIA OF MEDICINE

Diuretics (water pills) or other medicines that lower
the amount of potassium in the body may increase
the side effects of digitalis drugs.



Medicines that increase the amount of potassium in
the body may raise the risk of serious heart rhythm
problems when taken with digitalis drugs.



Diarrhea medicine or cholesterol-lowering drugs
such as cholestyramine (Questran) and colestipol
(Colestid) may keep digitalis medicines from being
absorbed into the body. To prevent this problem,
digitalis drugs should be taken several hours before
or after taking these medicines.

The list above does not include every drug that
may interact with digitalis drugs. Be sure to check with
a physician or pharmacist before taking any other
prescription or nonprescription (over-the-counter)
medicine.
In addition, a diet high in fiber may interfere with
the effects of digitalis drugs by preventing the medicine
from being absorbed into the body. To avoid this
problem, eat high fiber foods (such as bran products,
whole wheat bread, and fresh fruits and vegetables)
several hours before or after taking digitalis medicine.

Description
D & C is usually performed under general anesthesia, although local or epidural anesthesia can also be
used. A local lessens risk and costs, but the woman will
feel cramping during the procedure. The type of anesthesia used often depends upon the reason for the D & C.
In the procedure (which takes only minutes to
perform), the doctor inserts an instrument to hold
open the vaginal walls, and then stretches the opening
of the uterus to the vagina (the cervix) by inserting a
series of tapering rods, each thicker than the previous
one, or by using other specialized instruments. This
process of opening the cervix is called dilation.
Once the cervix is dilated, the physician inserts a
spoon-shaped surgical device called a curette into the
uterus. The curette is used to scrape away the uterine
lining. One or more small tissue samples from the
lining of the uterus or the cervical canal are sent for
analysis by microscope to check for abnormal cells.
Although simpler, less expensive techniques such
as a vacuum aspiration are quickly replacing the D &
C as a diagnostic method, it is still often used to
diagnose and treat a number of conditions.

Nancy Ross-Flanigan

Digoxin see Digitalis drugs; Antiarrhythmic
drugs

I Dilatation and curettage
Definition
Dilatation and curettage (D & C) is a gynecological procedure in which the lining of the uterus (endometrium) is scraped away.

Purpose
D & C is commonly used to obtain tissue for
microscopic evaluation to rule out cancer. D & C
may also be used to diagnose and treat heavy menstrual
bleeding, and to diagnose endometrial polyps and
uterine fibroids. A D & C can be used as a treatment
as well, to remove pregnancy tissue after a miscarriage,
incomplete abortion, or childbirth. Endometrial polyps
may be removed, and sometimes benign uterine tumors
(fibroids) may be scraped away. D & C can also be used
as an early abortion technique up to 16 weeks.
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
Because opening the cervix can be painful, sedatives may be given before the procedure begins. Deep
breathing and other relaxation techniques may help
ease cramping during cervical dilation.

Aftercare
A woman who has had a D & C performed in a
hospital can usually go home the same day or the next
day. Many women experience backache and mild
cramps after the procedure, and may pass small
blood clots for a day or so. Vaginal staining or bleeding
may continue for several weeks.
Most women can resume normal activities almost
immediately. Patients should avoid sexual intercourse,
douching, and tampon use for at least two weeks to
prevent infection while the cervix is closing and to
allow the endometrium to heal completely.

Risks
The primary risk after the procedure is infection.
Signs of infection include:


fever



heavy bleeding
1183

Dilatation and curettage



Dilatation and curettage

Uterus

Cervix
Vagina

~=====·CLCC_ _ _)
Dilator
Figure A

Curette
Figure B

Dilatation and curettage (D & C) is used primarily to diagnose and treat heavy menstrual bleeding and to diagnose endometrial
polyps, uterine fibroids, uterine cancer and cervical cancer. When performing a D & C, the physician inserts a speculum to
separate and hold the vaginal walls, then stretches open the cervix with a dilator. Once the cervix is dilated, the physician will
insert a curette into the uterus and scrape away small portions of the uterine lining for laboratory analysis. (Illustration by
Electronic Illustrators Group.)

KEY TERMS
Endometrial polyps—A growth in the lining of the
uterus (endometrium) that may cause bleeding and
can develop into cancer.
Epidural anesthesia—A type of anesthesia that is
injected into the epidural space of the spinal cord to
numb the nerves leading to the lower half of the
body.
Uterine fibroid—A noncancerous tumor of the
uterus that can range from the size of a pea to
the size of a grapefruit. Small fibroids require no
treatment, but those causing serious symptoms may
need to be removed.

complications include puncture of the uterus (which
usually heals on its own) or puncture of the bowel or
bladder (which require further surgery to repair).

Normal results
Removal of the uterine lining causes no side effects,
and may be beneficial if the lining has thickened so much
that it causes heavy periods. The uterine lining soon
grows again normally, as part of the menstrual cycle.
Resources
BOOKS

Carlson, Karen J., Stephanie A. Eisenstat, and Terra
Ziporyn. The Harvard Guide to Women’s Health.
Cambridge, MA: Harvard University Press, 1996.

Carol A. Turkington


severe cramps



foul-smelling vaginal discharge

A woman should report any of these symptoms to
her doctor, who can treat the infection with antibiotics
before it becomes serious.
D & C is a surgical operation, which carries certain risks associated with general anesthesia. Rare
1184

Dilated cardiomyopathy see Congestive
cardiomyopathy
Diltiazem see Calcium channel blockers
Dilution test see Kidney function tests
Diphenhydramine see Antihistamines
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Diphtheria is a potentially fatal, contagious disease that usually involves the nose, throat, and air
passages, but may also infect the skin. Its most striking
feature is the formation of a grayish membrane covering the tonsils and upper part of the throat.

Description
Like many other upper respiratory diseases,
diphtheria is most likely to break out during the winter
months. At one time it was a major childhood killer,
but it is now rare in developed countries because of
widespread immunization. Since 1988, all confirmed
cases in the United States have involved visitors or
immigrants. In countries that do not have routine
immunization against this infection, the mortality
rate varies from 1.5–25%.
Persons who have not been immunized may get
diphtheria at any age. The disease is spread most often
by droplets from the coughing or sneezing of an
infected person or carrier. The incubation period is
two to seven days, with an average of three days. It is
vital to seek medical help at once when diphtheria
is suspected, because treatment requires emergency
measures for adults as well as children.

Causes and symptoms
The symptoms of diphtheria are caused by toxins
produced by the diphtheria bacillus, Corynebacterium
diphtheriae (from the Greek for ‘‘rubber membrane’’).
In fact, toxin production is related to infections of the
bacillus itself with a particular bacteria virus called a
phage (from bacteriophage; a virus that infects bacteria). The intoxication destroys healthy tissue in the
upper area of the throat around the tonsils, or in open
wounds in the skin. Fluid from the dying cells then
coagulates to form the telltale gray or grayish green
membrane. Inside the membrane, the bacteria produce
an exotoxin, which is a poisonous secretion that causes
the life-threatening symptoms of diphtheria. The exotoxin is carried throughout the body in the bloodstream, destroying healthy tissue in other parts of the
body.
The most serious complications caused by the
exotoxin are inflammations of the heart muscle (myocarditis) and damage to the nervous system. The risk
of serious complications is increased as the time
between onset of symptoms and the administration
GALE ENCYCLOPEDIA OF MEDICINE

The signs and symptoms of diphtheria vary
according to the location of the infection:
Nasal
Nasal diphtheria produces few symptoms other
than a watery or bloody discharge. On examination,
there may be a small visible membrane in the nasal
passages. Nasal infection rarely causes complications
by itself, but it is a public health problem because it
spreads the disease more rapidly than other forms of
diphtheria.
Pharyngeal
Pharyngeal diphtheria gets its name from the
pharynx, which is the part of the upper throat that
connects the mouth and nasal passages with the voice
box. This is the most common form of diphtheria,
causing the characteristic throat membrane. The
membrane often bleeds if it is scraped or cut. It is
important not to try to remove the membrane because
the trauma may increase the body’s absorption of
the exotoxin. Other signs and symptoms of pharyngeal
diphtheria include mild sore throat, fever of
101–102 8F (38.3–38.9 8C), a rapid pulse, and general
body weakness.
Laryngeal
Laryngeal diphtheria, which involves the voice
box or larynx, is the form most likely to produce
serious complications. The fever is usually higher in
this form of diphtheria (103–104 8F or 39.4–40 8C)
and the patient is very weak. Patients may have a
severe cough, have difficulty breathing, or lose their
voice completely. The development of a ‘‘bull neck’’
indicates a high level of exotoxin in the bloodstream.
Obstruction of the airway may result in respiratory
compromise and death.
Skin
This form of diphtheria, which is sometimes called
cutaneous diphtheria, accounts for about 33% of
diphtheria cases. It is found chiefly among people
1185

Diphtheria

I Diphtheria

of antitoxin increases, and as the size of the membrane
formed increases. The myocarditis may cause disturbances in the heart rhythm and may culminate in heart
failure. The symptoms of nervous system involvement
can include seeing double (diplopia), painful or difficult swallowing, and slurred speech or loss of voice,
which are all indications of the exotoxin’s effect on
nerve functions. The exotoxin may also cause severe
swelling in the neck (‘‘bull neck’’).

Diphtheria

with poor hygiene. Any break in the skin can become
infected with diphtheria. The infected tissue develops
an ulcerated area and a diphtheria membrane may
form over the wound but is not always present. The
wound or ulcer is slow to heal and may be numb or
insensitive when touched.

Diagnosis
Because diphtheria must be treated as quickly as
possible, doctors usually make the diagnosis on the
basis of the visible symptoms without waiting for test
results.
In making the diagnosis, the doctor examines the
patient’s eyes, ears, nose, and throat in order to rule
out other diseases that may cause fever and sore
throat, such as infectious mononucleosis, a sinus infection, or strep throat. The most important single symptom that suggests diphtheria is the membrane. When a
patient develops skin infections during an outbreak of
diphtheria, the doctor will consider the possibility of
cutaneous diphtheria and take a smear to confirm the
diagnosis.
Laboratory tests
The diagnosis of diphtheria can be confirmed by
the results of a culture obtained from the infected area.
Material from the swab is put on a microscope slide
and stained using a procedure called Gram’s stain. The
diphtheria bacillus is called Gram-positive because it
holds the dye after the slide is rinsed with alcohol.
Under the microscope, diphtheria bacilli look like
beaded rod-shaped cells, grouped in patterns that
resemble Chinese characters. Another laboratory test
involves growing the diphtheria bacillus on a special
material called Loeffler’s medium.

Treatment
Diphtheria is a serious disease requiring hospital
treatment in an intensive care unit if the patient has
developed respiratory symptoms. Treatment includes
a combination of medications and supportive care:
Antitoxin
The most important step is prompt administration of diphtheria antitoxin, without waiting for
laboratory results. The antitoxin is made from horse
serum and works by neutralizing any circulating exotoxin. The doctor must first test the patient for sensitivity to animal serum. Patients who are sensitive
(about 10%) must be desensitized with diluted antitoxin, since the antitoxin is the only specific substance
1186

that will counteract diphtheria exotoxin. No human
antitoxin is available for the treatment of diphtheria.
The dose ranges from 20,000–100,000 units,
depending on the severity and length of time of symptoms occurring before treatment. Diphtheria antitoxin
is usually given intravenously.
Antibiotics
Antibiotics are given to wipe out the bacteria, to
prevent the spread of the disease, and to protect the
patient from developing pneumonia. They are not a
substitute for treatment with antitoxin. Both adults
and children may be given penicillin, ampicillin, or
erythromycin. Erythromycin appears to be more effective than penicillin in treating people who are carriers
because of better penetration into the infected area.
Cutaneous diphtheria is usually treated by cleansing the wound thoroughly with soap and water, and
giving the patient antibiotics for 10 days.
Supportive care
Diphtheria patients need bed rest with intensive
nursing care, including extra fluids, oxygenation, and
monitoring for possible heart problems, airway blockage, or involvement of the nervous system. Patients
with laryngeal diphtheria are kept in a croup tent or
high-humidity environment; they may also need
throat suctioning or emergency surgery if their airway
is blocked.
Patients recovering from diphtheria should rest at
home for a minimum of two to three weeks, especially if
they have heart complications. In addition, patients
should be immunized against diphtheria after recovery,
because having the disease does not always induce antitoxin formation and protect them from reinfection.
Prevention of complications
Diphtheria patients who develop myocarditis may
be treated with oxygen and with medications to prevent irregular heart rhythms. An artificial pacemaker
may be needed. Patients with difficulty swallowing can
be fed through a tube inserted into the stomach
through the nose. Patients who cannot breathe are
usually put on mechanical respirators.

Prognosis
The prognosis depends on the size and location of
the membrane and on early treatment with antitoxin;
the longer the delay, the higher the death rate. The
most vulnerable patients are children under age 15 and
GALE ENCYCLOPEDIA OF MEDICINE

Antitoxin—An antibody against an exotoxin,
usually derived from horse serum.
Bacillus—A rod-shaped bacterium, such as the
diphtheria bacterium.
Carrier—A person who may harbor an organism
without symptoms and may transmit it to others.
Cutaneous—Located in the skin.
Diphtheria-tetanus-pertussis (DTP)—The standard
preparation used to immunize children against
diphtheria, tetanus, and whooping cough. A so-called
‘‘acellular pertussis’’ vaccine (aP) is usually used since
its release in the mid-1990s.
Exotoxin—A poisonous secretion produced by
bacilli which is carried in the bloodstream to
other parts of the body.
Gram’s stain—A dye staining technique used in
laboratory tests to determine the presence and
type of bacteria.
Loeffler’s medium—A special substance used to
grow diphtheria bacilli to confirm the diagnosis.
Myocarditis—Inflammation of the heart tissue.

they are no longer contagious. Children placed in isolation are usually assigned a primary nurse for emotional support.
Identification and treatment of contacts
Because diphtheria is highly contagious and has a
short incubation period, family members and other
contacts of diphtheria patients must be watched for
symptoms and tested to see if they are carriers. They
are usually given antibiotics for seven days and a
booster shot of diphtheria/tetanus toxoid.
Reporting cases to public health authorities
Reporting is necessary to track potential epidemics, to help doctors identify the specific strain of
diphtheria, and to see if resistance to penicillin or
erythromycin has developed.
Resources
BOOKS

Chambers, Henry F. ‘‘Infectious Diseases: Bacterial &
Chlamydial.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Toxoid—A preparation made from inactivated
exotoxin, used in immunization.

Diplegia see Paralysis
those who develop pneumonia or myocarditis. Nasal
and cutaneous diphtheria are rarely fatal.

Direct Coombs’ test see Coombs’ tests
Direct laryngoscopy see Laryngoscopy

Prevention
Prevention of diphtheria has four aspects:
Immunization
Universal immunization is the most effective
means of preventing diphtheria. The standard course
of immunization for healthy children is three doses of
DPT (diphtheria-tetanus-pertussis) preparation given
between two months and six months of age, with
booster doses given at 18 months and at entry into
school. Adults should be immunized at 10 year intervals with Td (tetanus-diphtheria) toxoid. A toxoid is a
bacterial toxin that is treated to make it harmless but
still can induce immunity to the disease.
Isolation of patients
Diphtheria patients must be isolated for one to
seven days or until two successive cultures show that
GALE ENCYCLOPEDIA OF MEDICINE

I Discoid lupus erythematosus
Definition
Discoid lupus erythematosus (DLE) is a disease
in which coin-shaped (discoid) red bumps appear on
the skin.

Description
The disease called discoid lupus erythematosus
only affects the skin, although similar discoid skin
lesions can occur in the serious disease called systemic
lupus erythematosus (SLE). Only about 10% of all
patients with DLE will go on to develop the multiorgan disease SLE.
The tendency to develop DLE seems to run in
families. Although men or women of any age can
1187

Discoid lupus erythematosus

KEY TERMS

Discoid lupus erythematosus

develop DLE, it occurs in women three times more
frequently than in men. The typical DLE patient is a
woman in her 30s.

Causes and symptoms
The cause of DLE is unknown. It is thought that
DLE (like SLE) may be an autoimmune disorder.
Autoimmune disorders are those that occur when cells
of the immune system are misdirected against the
body. Normally, immune cells work to recognize and
help destroy foreign invaders like bacteria, viruses,
and fungi. In autoimmune disorders, these cells mistakenly recognize various tissues of the body as foreign invaders, and attack and destroy these tissues. In
SLE, the misdirected immune cells are antibodies. In
DLE, the damaging cells are believed to be a type of
white blood cell called a T lymphocyte. The injury to
the skin results in inflammation and the characteristic
discoid lesions.
In DLE, the characteristic skin lesion is circular
and raised. The reddish rash is about 5–10 mm in
diameter, with the center often somewhat scaly and
lighter in color than the darker outer ring. The surface
of these lesions is sometimes described as ‘‘warty.’’
There is rarely any itching or pain associated with
discoid lesions. They tend to appear on the face, ears,
neck, scalp, chest, back, and arms. As DLE lesions
heal, they leave thickened, scarred areas of skin. When
the scalp is severely affected, there may be associated
hair loss (alopecia).
People with DLE tend to be quite sensitive to the
sun. They are more likely to get a sunburn, and the sun
is likely to worsen their discoid lesions.

Diagnosis
Diagnosis of DLE usually requires a skin biopsy.
A small sample of a discoid lesion is removed, specially
prepared, and examined under a microscope. Usually,
the lesion has certain microscopic characteristics that
allow it to be identified as a DLE lesion. Blood tests
will not reveal the type of antibodies present in SLE,
and physical examination usually does not reveal anything other than the skin lesions. If antibodies exist in
the blood, or if other symptoms or physical signs are
found, it is possible that the discoid lesions are a sign
of SLE rather than DLE.

Treatment
Treatment of DLE primarily involves the use of a
variety of skin creams. Sunscreens are used for
1188

Discoloration of the hands is one characteristic of discoid
lupus erythematosus. (Custom Medical Stock Photo.
Reproduced by permission.)

KEY TERMS
Antibody—Specialized cells of the immune system
that can recognize organisms invading the body
(like bacteria, viruses, and fungi). The antibodies
are then able to start a complex chain of events
designed to kill these foreign invaders.
Autoimmune disorder—A disorder in which the
body’s antibodies mistake the body’s own tissues
for foreign invaders. The immune system then
attacks and causes damage to these tissues.
Immune system—The system of specialized organs,
lymph nodes, and blood cells throughout the body
that work together to defend the body against foreign
invaders (bacteria, viruses, fungi, etc.).

protection. Steroid creams can be applied to decrease
inflammation. Occasionally, small amounts of a steroid preparation will be injected with a needle into a
specific lesion. Because of their long list of side effects,
steroid preparations taken by mouth are avoided.
Sometimes, short-term treatment with oral steroids
will be used for particularly severe DLE outbreaks.
Medications used to treat the infectious disease
malaria are often used to treat DLE.

Alternative treatment
Alternative treatments for DLE include eating a
healthy diet, low in red meat and dairy products and
high in fish containing omega-3 fatty acids. These
types of fish include mackerel, sardines, and salmon.
Following a healthy diet is thought to decrease
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
For the most part, the prognosis for people with
DLE is excellent. While the lesions may be cosmetically unsightly, they are not life threatening and
usually do not cause a patient to change his or her
lifestyle. Only about 10% of patients with DLE will go
on to develop SLE.

Prevention
DLE cannot be prevented. Recommendations to
prevent flares of DLE in patients with the disease
include avoiding exposure to sun and consistently
using sunscreen.
Resources

and that has not responded to conservative treatment.
Surgery is also performed if there is pressure on the
lumbosacral nerve roots that causes weakness or
bowel or bladder disfunction.
As a person ages, the disks between the vertebrae
degenerate and dry out, and the fibers holding them in
place tear. Eventually, the disk can form a blister-like
bulge, compressing nerves in the spine and causing pain.
This is called a ‘‘prolapsed’’ (or herniated) disk. If such
a disk causes muscle weakness or interferes with bladder
or bowel function because it is pressing on a nerve root,
immediate surgery to remove the disk may be needed.
The aim of the surgery is to try to relieve all
pressure on nerve roots by removing the pulpy material from the disk, or the disk itself. If it is necessary to
remove material from several nearby vertebrae, the
spine may become unsteady. In this case, the surgeon
will perform a spinal fusion, removing all the disks
between two or more vertebrae and roughening the
bones so that the vertebrae heal together. Bone strips
taken from the patient’s leg or hip may be used to help
hold the vertebrae together. Spinal fusion decreases
pain but it also decreases spinal mobility.

ORGANIZATIONS

The American College of Rheumatology. 1800 Century
Place, Suite 250, Atlanta, GA 30345. (404) 633-3777.
<http://www.rheumatology.org>.
Lupus Foundation of America. 1300 Piccard Dr., Suite 200,
Rockville, MD 20850. (800) 558-0121. <http://
www.lupus.org>.

Rosalyn Carson-DeWitt, MD

Precautions
The doctor will obtain x rays, neuroimaging studies, including computed tomography scan (CT scan)
myelogram and magnetic resonance imaging (MRI),
and clinical exams to determine the precise location
of the affected disk.

Description

I Disk removal
Definition
One of the most common types of back surgery is
disk removal (diskectomy), the removal of an intervertebral disk, the flexible plate that connects any two
adjacent vertebrae in the spine. Intervertebral disks act
as shock absorbers, protecting the brain and spinal cord
from the impact produced by the body’s movements.

The surgery is done under general anaesthesia,
which puts the patient to sleep and affects the whole
body. Operating on the patient’s back, the neurosurgeon or orthopedic surgeon makes an opening
into the vertebral canal, and then moves the dura and
the bundle of nerves called the ‘‘cauda equina’’ (horse’s
tail) aside, which exposes the disk. If a portion of the
disk has moved from between the vertebrae out into the
nerve canal, it is simply removed. If the disk itself has
become fragmented and partially displaced, or not
fragmented but bulging extensively, the surgeon will
remove the bulging or displaced part of the disk and
the part that lies in the space between the vertebrae.

Purpose
About 150,000 Americans undergo disk removal
each year in the United States. Removing the invertebral disk is performed to treat back pain that has
lasted at least six weeks as a result of an abnormal disk
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
The patient is given an injection an hour before
the surgery to dry up internal fluids and encourage
drowsiness.
1189

Disk removal

inflammation. Dietary supplements believed to be
helpful include vitamins B, C, E, and selenium.
Vitamin A is also recommended to improve DLE
lesions. Constitutional homeopathic treatment can
help heal DLE as well as help prevent it developing
into SLE.

Dislocations and subluxations

KEY TERMS
Diskectomy—The surgical removal of a portion of
an intervertebral disk.
Dura—The strongest and outermost of three membranes that protect the brain, spinal cord, and
nerves of the cauda equina.
Herniated disk—A blisterlike bulging or protrusion
of the contents of the disk out through the fibers that
normally hold them in place. It is also called a
ruptured disk, slipped disk, or displaced disk.
Intervertebral disk—Cylindrical elastic-like gel
pads that separate and join each pair of vertebrae
in the spine.
Laminectomy—An operation in which the surgeon
cuts through the covering of a vertebra to reach a
herniated disk in order to remove it.
Vertebra—The bones that make up the back bone
(spine).

Aftercare
After the operation, the patient will awaken lying
flat and face down, and must remain this way for
several days, changing position only to avoid bedsores. There maybe slight pain or stiffness in the
back area.
Patients should sleep on a firm mattress and avoid
bending at the waist, lifting heavy weights, or sitting in
one spot for a long time (such as riding in a car).
After surgery, patients can usually leave the hospital on the fourth or fifth day. They must:


avoid sitting for more than 15–20 minutes



use a reclined chair



avoid bending, twisting, or lifting



begin gentle walking (indoors or outdoors), gradually increasing



begin stationary biking or gentle swimming after two
weeks



continue exercise for the next four weeks



slow down if they experience more than minor pain
in the back or leg

Risks
All surgery carries some risk due to heart and lung
problems or the anesthesia itself, but this risk is
1190

generally extremely small. (The risk of death from
general anesthesia for all types of surgery, for example, is only about 1 in 1,600.)
The most common risk of the surgery is infection,
which occurs in 1–2% of cases. Rarely, the surgery can
damage nerves in the lower back or major blood vessels in front of the disk. Occasionally, there may be
some residual paralysis of a particular leg or bladder
muscle after surgery, but this is the result of the disk
problem that necessitated the surgery, not the operation itself.
While disk removals can relieve pain in 90% of
cases, there are some people who do not get pain relief,
depending on how long they had the condition requiring surgery and other factors.

Normal results
After about five days, most patients can leave the
hospital. They can resume all normal activities, including work, after four to six weeks of recuperation at
home.
In properly evaluated patients, there is a very
good chance that disk removal will be successful in
easing pain. Even in patients over age 60, disk surgery
has a ‘‘good to excellent’’ result for 87% of patients.
Disk surgery can relieve both back and leg pain, but
the greatest pain relief will occur with the leg pain.
Resources
BOOKS

Younson, Robert M., et al., editors. The Surgery Book: An
Illustrated Guide to 73 of the Most Common Operations.
New York: St. Martin’s Press, 1993.

Carol A. Turkington

Diskectomy see Disk removal

I Dislocations and subluxations
Definition
In medicine, the terms dislocation and subluxation refer to the displacement of bones that form a
joint. These conditions affecting the joint most often
result from trauma that causes adjoining bones to no
longer align with each other. A partial or incomplete
dislocation is called a subluxation.
GALE ENCYCLOPEDIA OF MEDICINE

Dislocations and subluxations

Description
In a healthy joint, the bones are normally held
together with tough, fibrous bands called ligaments.
These ligaments are attached to each bone along with
a fibrous sac surrounding the joint called the articular
capsule or joint capsule. The ligaments and joint capsule
are relatively strong and nonelastic but permit movement within normal limits for each particular joint. In
the event of a dislocation, one of the bones making up
the joint is forced out of its natural alignment from
excessive stretching and tearing of the joint ligaments
and capsule. Muscles and tendons surrounding the joint
are usually stretched and injured to some degree.

Causes and symptoms
A violent movement at the joint that exceeds normal limits usually causes a joint dislocation. Although
dislocations often result from trauma, they sometimes
occur as a result of disease affecting the joint structures.
In the process of the dislocation, there is tearing of the
ligaments and the articular capsule, which are vital
structures for connecting the bone. Following a dislocation, the bones affected are often immobile and the
affected limb may be locked in an abnormal position;
fractures are also a concern with severe dislocations.
Important factors in recognizing a dislocation or
subluxation include a history of experiencing a fall or
receiving a blow in a particular joint followed by the
sudden onset of loss of function to the involved limb.
Immediately after the dislocation, the joint almost
always swells significantly and feels painful when pressure is applied (point tenderness). If trauma to the
joint causing the dislocation or subluxation is violent
in nature, small chips of bone can be torn away with
the supporting structures. Chronic recurrent dislocations may take place without severe pain because of
the somewhat slack condition of the surrounding muscles and other supporting tissues. A first-time dislocation is considered and treated as a possible fracture.
Risk factors that can increase susceptibility of joint
dislocation and subluxation are shallow or abnormally formed joint surfaces present at birth (congenital) and/or other diseases of ligaments and tissue
around a joint. Some infants are born with a hip dislocation. Both sexes and all ages are affected.

Diagnosis
A thorough medical history and physical exam by a
physician is the first step in the correct diagnosis of
dislocations and subluxations. X rays of the joint and
adjacent bones can locate and help determine the extent
of dislocated joints.
GALE ENCYCLOPEDIA OF MEDICINE

This x ray shows the dislocation between two bones in a
finger. (Photo Researchers, Inc. Reproduced by permission.)

Treatment
Immediately after the dislocation, the application
of ice is helpful to control swelling and decrease pain.
If the patient needs to be transported, it is important to
prevent the joint from moving (immobilization). At
times, a cast or splint may be used to immobilize the
joint and ensure proper alignment and healing. The
treatment of realigning bones following a dislocation
is called reduction. This may include simple maneuvers that manipulate the joint to reposition the bones
or surgical procedures to restore the joint to its normal
position. A general anesthesia or muscle relaxant may
be used to help make joint reduction possible by relaxing surrounding muscles in spasm. Acetaminophen or
aspirin are sometimes used to control moderate pain,
and narcotics may be prescribed by the physician if the
pain is severe. Recurring dislocation may require surgical reconstruction or replacement of the joint. It is
not recommended to attempt to reset a dislocated joint
1191

Dislocations and subluxations

Anterior temporal
mandibular dislocation

Subcoracoid
dislocation (shoulder)

Posterior dislocation of hip

Dislocation of thumb

Dislocations and subluxations refer to the displacement of bones that form a joint. Such conditions most often result from
trauma causing adjoining bones to no longer touch each other. A partial or incomplete dislocation is called a subluxation. The
illustrations above indicate dislocation of the jaw bone, shoulder blade, hip bone, and the thumb. (Illustration by Electronic
Illustrators Group.)

outside of a medical environment with experienced
medical personnel, because a fracture may be present.

Alternative treatment
Chiropractic care has been shown to be effective
for joint subluxation and dislocation, especially in the
spine. Swelling can be addressed using botanical therapies. Bromelain, a pineapple enzyme, and turmeric
(Curcuma longa) are the most potent botanical remedies for this purpose. Acute homeopathic care with
arnica (Arnica montana) can reduce the trauma to the
body. Ligament and tendon strengthening can be
assisted both botanically and homeopathically.

Prognosis
Joint ligaments have poor blood supply and,
therefore, heal slowly. This healing process continues
long after the symptoms of the dislocation injury have
diminished. Once a joint has been either subluxated or
1192

completely dislocated, the connective tissue binding or
holding it in correct alignment is stretched to such an
extent that the joint becomes extremely vulnerable to
repeated dislocations. However, this chance of recurrent dislocation and subluxation will decrease if a
proper rehabilitation program is implemented to
strengthen surrounding muscles of the joint. Most
joint dislocations are curable with prompt treatment.
After the dislocation has been corrected, the joint may
require immobilization with a cast or sling for two to
eight weeks.

Prevention
When an individual is involved in strenuous
sports or heavy work, involved joints may be protected by elastic bandage wraps, tape wraps, knee
and shoulder pads, or special support stockings.
Keeping the muscles surrounding the joint strong
will also help prevent dislocations. Long-term problems may also be prevented by allowing an adequate
GALE ENCYCLOPEDIA OF MEDICINE

Articular capsule—An envelope of tissue that
surrounds a free moving joint, composed of an
external layer of white fibrous tissue and an external synovial membrane that secretes a lubricant
into the joint.

amount of time for an injured joint to rest and heal
prior to resuming full activity.
Resources
OTHER

Griffith, H. Winter. ‘‘Dislocations or Subluxation.’’
Thrive Online. 1998. [cited March 25, 1998]. <http://
thriveonline.oxygen.com>.

Jeffrey P. Larson, RPT

Disopyramide see Antiarrhythmic drugs
Disproportionate dwarfism see
Achondroplasia
Dissecting aneurysm see Aortic dissection
Dissecting hematoma see Aortic dissection
Disseminated lupus erythematosus see
Systemic lupus erythematosus

I Dissociative disorders
Definition
The dissociative disorders are a group of mental
disorders that affect consciousness defined as causing significant interference with the patient’s general
functioning, including social relationships and
employment.

Description
In order to have a clear picture of these disorders,
dissociation should first be understood. Dissociation
is a mechanism that allows the mind to separate or
compartmentalize certain memories or thoughts from
normal consciousness. These split-off mental contents
are not erased. They may resurface spontaneously or
be triggered by objects or events in the person’s
environment.
GALE ENCYCLOPEDIA OF MEDICINE

Dissociation is a process that occurs along a spectrum of severity. It does not necessarily mean that a
person has a dissociative disorder or other mental illness.
A mild degree of dissociation occurs with some physical
stressors; people who have gone without sleep for a long
period of time, have had ‘‘laughing gas’’ for dental surgery, or have been in a minor accident often have brief
dissociative experiences. Another commonplace example of dissociation is a person becoming involved in a
book or movie so completely that the surroundings or
the passage of time are not noticed. Another example
might be driving on the highway and taking several exits
without noticing or remembering. Dissociation is related
to hypnosis in that hypnotic trance also involves a temporarily altered state of consciousness. Most patients
with dissociative disorders are highly hypnotizable.
People in other cultures sometimes have dissociative experiences in the course of religious (in certain
trance states) or other group activities. These occurrences should not be judged in terms of what is considered ‘‘normal’’ in the United States.
Moderate or severe forms of dissociation are
caused by such traumatic experiences as childhood
abuse, combat, criminal attacks, brainwashing in hostage situations, or involvement in a natural or transportation disaster. Patients with acute stress disorder,
post-traumatic stress disorder (PTSD), or conversion
disorder and somatization disorder may develop dissociative symptoms. Recent studies of trauma indicate
that the human brain stores traumatic memories in a
different way than normal memories. Traumatic memories are not processed or integrated into a person’s
ongoing life in the same fashion as normal memories.
Instead they are dissociated, or ‘‘split off,’’ and may
erupt into consciousness from time to time without
warning. The affected person cannot control or ‘‘edit’’
these memories. Over a period of time, these two sets of
memories, the normal and the traumatic, may coexist as
parallel sets without being combined or blended. In
extreme cases, different sets of dissociated memories
may alter subpersonalities of patients with dissociative
identity disorder (multiple personality disorder).
The dissociative disorders vary in their severity and
the suddenness of onset. It is difficult to give statistics
for their frequency in the United States because they are
a relatively new category and are often misdiagnosed.
Criteria for diagnosis require significant impairment
in social or vocational functioning.
Dissociative amnesia
Dissociative amnesia is a disorder in which the
distinctive feature is the patient’s inability to
1193

Dissociative disorders

KEY TERMS

Dissociative disorders

remember important personal information to a degree
that cannot be explained by normal forgetfulness. In
many cases, it is a reaction to a traumatic accident or
witnessing a violent crime. Patients with dissociative
amnesia may develop depersonalization or trance
states as part of the disorder, but they do not experience a change in identity.
Dissociative fugue
Dissociative fugue is a disorder in which a person
temporarily loses his or her sense of personal identity
and travels to another location where he or she may
assume a new identity. Again, this condition usually
follows a major stressor or trauma. Apart from inability to recall their past or personal information,
patients with dissociative fugue do not behave strangely or appear disturbed to others. Cases of dissociative fugue are more common in wartime or in
communities disrupted by a natural disaster.



an innate ability to dissociate easily



repeated episodes of severe physical or sexual abuse
in childhood



the lack of a supportive or comforting person to
counteract abusive relative(s)



the influence of other relatives with dissociative
symptoms or disorders

The relationship of dissociative disorders to childhood abuse has led to intense controversy and lawsuits
concerning the accuracy of childhood memories. The
brain’s storage, retrieval, and interpretation of memories are still not fully understood. Controversy also
exists regarding how much individuals presenting dissociative disorders have been influenced by books and
movies to describe a certain set of symptoms
(scripting).
The major dissociative symptoms are:
Amnesia

Depersonalization disorder
Depersonalization disorder is a disturbance in
which the patient’s primary symptom is a sense of
detachment from the self. Depersonalization as a symptom (not as a disorder) is quite common in college-age
populations. It is often associated with sleep deprivation or ‘‘recreational’’ drug use. It may be accompanied
by ‘‘derealization’’ (where objects in an environment
appear altered). Patients sometimes describe
depersonalization as feeling like a robot or watching
themselves from the outside. Depersonalization disorder may also involve feelings of numbness or loss of
emotional ‘‘aliveness.’’

Amnesia in a dissociative disorder is marked by
gaps in a patient’s memory for long periods of time or
for traumatic events. Doctors can distinguish this type
of amnesia from loss of memory caused by head injuries or drug intoxication, because the amnesia is
‘‘spotty’’ and related to highly charged events and
feelings.
Depersonalization
Depersonalization is a dissociative symptom in
which the patient feels that his or her body is unreal,
is changing, or is dissolving. Some patients experience
depersonalization as being outside their bodies or
watching a movie of themselves.

Dissociative identity disorder (DID)
Dissociative identity disorder (DID) is the newer
name for multiple personality disorder (MPD). DID is
considered the most severe dissociative disorder and
involves all of the major dissociative symptoms.
Dissociative disorder not otherwise specified
(DDNOS)
DDNOS is a diagnostic category ascribed to
patients with dissociative symptoms that do not meet
the full criteria for a specific dissociative disorder.

Causes and symptoms
The moderate to severe dissociation that occurs in
patients with dissociative disorders is understood to
result from a set of causes:
1194

Derealization
Derealization is a dissociative symptom in which
the external environment is perceived as unreal. The
patient may see walls, buildings, or other objects as
changing in shape, size, or color. In some cases, the
patient may feel that other persons are machines or
robots, though the patient is able to acknowledge the
unreality of this feeling.
Identity disturbances
Patients with dissociative fugue, DDNOS, or DID
often experience confusion about their identities or
even assume new identities. Identity disturbances
result from the patient having split off entire personality traits or characteristics as well as memories.
When a stressful or traumatic experience triggers the
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
When a doctor is evaluating a patient with dissociative symptoms, he or she will first rule out physical
conditions that sometimes produce amnesia, depersonalization, or derealization. These physical conditions
include epilepsy, head injuries, brain disease, side
effects of medications, substance abuse, intoxication,
AIDS, dementia complex, or recent periods of extreme
physical stress and sleeplessness. In some cases, the
doctor may give the patient an electroencephalogram
(EEG) to exclude epilepsy or other seizure disorders.
If the patient appears to be physically normal, the
doctor will rule out psychotic disturbances, including
schizophrenia. In addition, doctors can use some psychological tests to narrow the diagnosis. One is a screener,
the Dissociative Experiences Scale (DES). If the patient
has a high score on this test, he or she can be evaluated
further with the Dissociative Disorders Interview
Schedule (DDIS) or the Structured Clinical Interview
for DSM-IV Dissociative Disorders (SCID-D). It is also
possible for doctors to measure a patient’s hypnotizability as part of a diagnostic evaluation.

Treatment

KEY TERMS
Amnesia—A general medical term for loss of memory that is not due to ordinary forgetfulness.
Amnesia can be caused by head injuries, brain
disease, or epilepsy, as well as by dissociation.
Depersonalization—A dissociative symptom in
which the patient feels that his or her body is
unreal, is changing, or is dissolving.
Derealization—A dissociative symptom in which
the external environment is perceived as unreal.
Dissociation—A psychological mechanism that
allows the mind to split off traumatic memories or
disturbing ideas from conscious awareness.
Fugue—A dissociative experience during which a
person travels away from home, has amnesia for
their past, and may be confused about their identity
but otherwise appear normal.
Hypnosis—The means by which a state of extreme
relaxation and suggestibility is induced: used to
treat amnesia and identity disturbances that occur
in dissociative disorders.
Multiple personality disorder (MPD)—An older
term for dissociative identity disorder (DID).
Trauma—A disastrous or life-threatening event that
can cause severe emotional distress, including dissociative symptoms and disorders.

Treatment of the dissociative disorders often combines several methods.
Psychotherapy
Patients with dissociative disorders often require
treatment by a therapist with some specialized understanding of dissociation. This background is particularly
important if the patient’s symptoms include identity
problems. Many patients with dissociative disorders
are helped by group as well as individual treatment.
Medications
Some doctors will prescribe tranquilizers or antidepressants for the anxiety and/or depression that often
accompany dissociative disorders. Patients with dissociative disorders are, however, at risk for abusing or
becoming dependent on medications. As of 2001, there
is no drug that can reliably counteract dissociation itself.

hypnosis is related to the process of dissociation.
Hypnosis may help patients recover repressed ideas
and memories. Therapists treating patients with DID
sometimes use hypnosis in the process of ‘‘fusing’’ the
patient’s alternate personalities.

Prognosis
Prognoses for dissociative disorders vary. Recovery
from dissociative fugue is usually rapid. Dissociative
amnesia may resolve quickly, but can become a chronic
disorder in some patients. Depersonalization disorder,
DDNOS, and DID are usually chronic conditions. DID
usually requires five or more years of treatment for
recovery.

Prevention
Hypnosis
Hypnosis is frequently recommended as a method
of treatment for dissociative disorders, partly because
GALE ENCYCLOPEDIA OF MEDICINE

Since the primary cause of dissociative disorders is
thought to involve extended periods of humanly
inflicted trauma, prevention depends on the
1195

Dissociative disorders

reemergence of these dissociated parts, the patient
may act differently, answer to a different name, or
appear confused by his or her surroundings.

Diuretics

elimination of child abuse and psychological abuse of
adult prisoners or hostages.
Resources
BOOKS

Eisendrath, Stuart J. ‘‘Psychiatric Disorders.’’ In Current
Medical Diagnosis and Treatment, 1998, edited by
Stephen McPhee, et al., 37th ed. Stamford: Appleton &
Lange, 1997.

Rebecca J. Frey, PhD

In addition, some medicines contain combinations of two diuretics. The brands Dyazide and
Maxzide, for example, contain the thiazide diuretic
hydrochlorothiazide with the potassium-sparing
diuretic triamterene.
Some nonprescription (over-the-counter) medicines contain diuretics. However, the medicines
described here cannot be bought without a physician’s
prescription. They are available in tablet, capsule,
liquid, and injectable forms.

Recommended dosage

Dissociative identity disorder see Multiple
personality disorder

I Diuretics
Definition
Diuretics are medicines that help reduce the
amount of water in the body.

Purpose
Diuretics are used to treat the buildup of excess
fluid in the body that occurs with some medical conditions such as congestive heart failure, liver disease,
and kidney disease. Some diuretics are also prescribed
to treat high blood pressure. These drugs act on the
kidneys to increase urine output. This reduces the
amount of fluid in the bloodstream, which in turn
lowers blood pressure.

Description
There are several types of diuretics, also called
water pills:


Loop diuretics, such as bumetanide (Bumex) and
furosemide (Lasix), get their name from the loopshaped part of the kidneys where they have their
effect.



Thiazide diuretics include such commonly used
diuretics as hydrochlorothiazide (HydroDIURIL,
Esidrix), chlorothiazide (Diuril), and chlorthalidone
(Hygroton).



Potassium-sparing diuretics prevent the loss of
potassium, which is a problem with other types
of diuretics. Examples of potassium-sparing diuretics are amiloride (Midamor) and triamterene
(Dyrenium).

1196

The recommended dosage depends on the type of
diuretic and may be different for different patients.
Check with the physician who prescribed the drug or
the pharmacist who filled the prescription for the correct dosage, and take the medicine exactly as directed.

Precautions
Seeing a physician regularly while taking a diuretic is important. The physician will check to make sure
the medicine is working as it should and will watch for
unwanted side effects.
Some people feel unusually tired when they first
start taking diuretics. This effect usually becomes less
noticeable over time, as the body adjusts to the
medicine.
Because diuretics increase urine output, people
who take this medicine may need to urinate more
often, even during the night. Health care professionals
can help patients schedule their doses to avoid interfering with their sleep or regular activities.
For patients taking the kinds of diuretics that rob
potassium from the body, physicians may recommend
adding potassium-rich foods or drinks, such as citrus
fruits and juices, to the diet. Or they may suggest
taking a potassium supplement or taking another
medicine that keeps the body from losing too much
potassium. If the physician recommends any of these
measures, be sure to closely follow his or her directions. Do not make other diet changes without checking with the physician. People who are taking
potassium-sparing diuretics should not add potassium
to their diets, as too much potassium may be harmful.
People who take diuretics may lose too much
water or potassium when they get sick, especially if
they have severe vomiting and diarrhea. They should
check with their physicians if they become ill.
These medicines make some people feel lightheaded, dizzy, or faint when they get up after sitting
GALE ENCYCLOPEDIA OF MEDICINE

Anyone who is taking a diuretic should be sure to
tell the health care professional in charge before having surgical or dental procedures, medical tests, or
emergency treatment.
Some diuretics make the skin more sensitive to
sunlight. Even brief exposure to sun can cause a severe
sunburn, itching, a rash, redness, or other changes in
skin color. While being treated with this medicine,
avoid being in direct sunlight, especially between
10 a.m. and 3 p.m.; wear a hat and tightly woven
clothing that covers the arms and legs; use a sunscreen
with a skin protection factor (SPF) of at least 15;
protect the lips with a sun block lipstick; and do not
use tanning beds, tanning booths, or sunlamps. People
with fair skin may need to use a sunscreen with a
higher skin protection factor.
Special conditions
People who have certain medical conditions or
who are taking certain other medicines may have problems if they take diuretics. Before taking these drugs,
be sure to let the physician know about any of these
conditions:
ALLERGIES. Anyone who has had unusual reac-

tions to diuretics or sulfonamides (sulfa drugs) in the
past should let his or her physician know before using
a diuretic. The physician should also be told about any
allergies to foods, dyes, preservatives, or other
substances.
PREGNANCY. Diuretics will not help the swelling

of hands and feet that some women have during pregnancy. In general, pregnant women should not use
diuretics unless a physician recommends their use.
Although studies have not been done on pregnant
women, studies of laboratory animals show that
some diuretics can cause harmful effects when taken
during pregnancy.
BREASTFEEDING. Some diuretics pass into breast
milk, but no reports exist of problems in nursing
babies whose mothers use this medicine. However,
thiazide diuretics may decrease the flow of breast
milk. Women who are breastfeeding and need to use
a diuretic should check with their physicians.

GALE ENCYCLOPEDIA OF MEDICINE

OTHER MEDICAL CONDITIONS. Side effects of
some diuretics may be more likely in people who
have had a recent heart attack or who have liver disease or severe kidney disease. Other diuretics may not
work properly in people with liver disease or severe
kidney disease. Diuretics may worsen certain medical
conditions, such as gout, kidney stones, pancreatitis,
lupus erythematosus, and hearing problems. In addition, people with diabetes should be aware that diuretics may increase blood sugar levels. People with heart
or blood vessel disease should know that some diuretics increase cholesterol or triglyceride levels. The risk
of an allergic reaction to certain diuretics is greater in
people with bronchial asthma. Before using diuretics,
people with any of these medical problems should
make sure their physicians are aware of their conditions. Also, people who have trouble urinating or who
have high potassium levels in their blood may not be
able to take diuretics and should check with a physician before using them.
USE OF CERTAIN MEDICINES. Taking diuretics with
certain other drugs may affect the way the drugs work
or may increase the chance of side effects.

Side effects
Some side effects, such as loss of appetite, nausea
and vomiting, stomach cramps, diarrhea, and dizziness, usually lessen or go away as the body adjusts to
the medicine. These problems do not need medical
attention unless they continue or interfere with normal
activities.
Patients taking potassium-sparing diuretics
should know the signs of too much potassium and
should check with a physician as soon as possible if
any of these symptoms occur:


irregular heartbeat



breathing problems



numbness or tingling in the hands, feet, or lips



confusion or nervousness



unusual tiredness or weakness



weak or heavy feeling in the legs

Patients taking diuretics that cause potassium loss
should know the signs of too little potassium and
should check with a physician as soon as possible if
they have any of these symptoms:


fast or irregular heartbeat



weak pulse



nausea or vomiting



dry mouth
1197

Diuretics

or lying down. Older people are especially likely to
have this problem. Drinking alcohol, exercising,
standing for long periods, or being in hot weather
may make the problem worse. To lessen the problem,
get up gradually and hold onto something for support
if possible. Avoid drinking too much alcohol and be
careful in hot weather or when exercising or standing
for a long time.

Diverticulosis and diverticulitis

Take the diuretic at least one hour before or four
hours after the cholesterol-lowering drug.

KEY TERMS


Cyclosporine (Sandimmune), a medicine that suppresses the immune system. Taking this medicine
with potassium-sparing diuretics may increase the
chance of side effects by causing levels of potassium
in the blood to be too high.



Potassium supplements, other medicines containing
potassium, or salt substitutes that contain potassium. Taking these with potassium-sparing diuretics
may lead to too much potassium in the blood,
increasing the chance of side effects.



Lithium, used to treat bipolar disorder (manicdepressive illness). Using this medicine with potassium-sparing diuretics may allow lithium to build up
to poisonous levels in the body.



Digitalis heart drugs, such as digoxin (Lanoxin).
Using this medicine with combination diuretics
such as triamterene-hydrocholorthiazide (Dyazide,
Maxzide) may cause blood levels of the heart medicine to be too high, making side effects such as
changes in heartbeat more likely.

Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Lupus erythematosus—A chronic disease that
affects the skin, joints, and certain internal organs.
Pancreas—A gland located beneath the stomach.
The pancreas produces juices that help break down
food.
Potassium—A mineral found in whole grains,
meat, legumes, and some fruits and vegetables.
Potassium is important for many body processes,
including proper functioning of the nerves and
muscles.
Triglyceride—A substance formed in the body
from fat in the diet. Triglycerides are the main
fatty materials in the blood. Together with protein,
they make up high- and low-density lipoproteins
(HDLs and LDLs). Triglyceride levels are important
in the diagnosis and treatment of many diseases
including high blood pressure, diabetes, and heart
disease.



excessive thirst



muscle cramps or pain



unusual tiredness or weakness



mental or mood changes

Interactions
Diuretics may interact with other medicines.
When this happens, the effects of one or both of the
drugs may change or the risk of side effects may be
greater. Anyone who takes a diuretic should let the
physician know all other medicines he or she is taking
and should ask whether the possible interactions can
interfere with drug therapy. Among the drugs that
may interact with diuretics are:


Angiotensin-converting enzyme (ACE) inhibitors,
such as benazepril (Lotensin), captopril (Capoten),
and enalapril (Vasotec), used to treat high blood pressure. Taking these drugs with potassium-sparing
diuretics may cause levels of potassium in the blood
to be too high, increasing the chance of side effects.



Cholesterol-lowering drugs such as cholestyramine
(Questran) and colestipol (Colestid). Taking these
drugs with combination diuretics such as Dyazide
and Maxzide may keep the diuretic from working.

1198

The list above does not include every drug that
may interact with diuretics. Check with a physician or
pharmacist before combining diuretics with any other
prescription or nonprescription (over-the-counter)
medicine.
Nancy Ross-Flanigan

Diverticulitis see Diverticulosis and
diverticulitis

and
I Diverticulosis
diverticulitis
Definition
Diverticulosis refers to a condition in which
the inner, lining layer of the large intestine (colon)
bulges out (herniates) through the outer, muscular
layer. These outpouchings are called diverticula.
Diverticulitis refers to the development of inflammation and infection in one or more diverticula.

Description
Diverticula tend to occur most frequently in the
last segment of the large intestine, the sigmoid colon.
They occur with decreasing frequency as one examines
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Diverticula are believed to be caused by overly
forceful contractions of the muscular wall of the
large intestine. As areas of this wall spasm, they
become weaker and weaker, allowing the inner lining
to bulge through. The anatomically weakest areas of
the intestinal wall occur next to blood vessels which
course through the wall, so diverticula commonly
occur in this location.
Diverticula are most common in the developed
countries of the West (North America, Great Britain,
northern and western Europe). This is thought to be due
to the diet of these countries, which tends to be quite low
in fiber. A diet low in fiber results in the production of
smaller volumes of stool. In order to move this smaller
stool along the colon and out of the rectum, the colon
must narrow itself significantly, and does so by contracting down forcefully. This causes an increase in pressure,
which, over time, weakens the muscular wall of the
intestine and allows diverticular pockets to develop.
The origin of giant diverticula development is not
completely understood, although one theory involves
gas repeatedly entering and becoming trapped in an
already-existing diverticulum, causing stretching and
expansion of that diverticulum.
The great majority of people with diverticulosis
will remain symptom-free. Many diverticula are quite
accidentally discovered during examinations for other
conditions of the intestinal tract.
Some people with diverticulosis have symptoms
such as constipation, cramping, and bloating. It is
unclear whether these symptoms are actually caused
by the diverticula themselves, or whether some other
gastrointestinal condition (such as irritable bowel syndrome) might be responsible. A complication of diverticulosis occurs because many diverticula develop in
areas very near blood vessels. Therefore, one serious
risk of diverticulosis involves bleeding. Although an
infrequent complication, the bleeding can be quite
severe. Seventy-five percent of such bleeding episodes
occur due to diverticula located on the right side of the
GALE ENCYCLOPEDIA OF MEDICINE

colon. About 50% of the time, such bleeding will stop
on its own.
One of the most common and potentially serious
complications of diverticulosis is inflammation and
infection of a particular diverticulum, called
diverticulitis.
Diverticulitis is three times more likely to occur in
the left side of the large intestine. Since most diverticula are located in the sigmoid colon (the final segment
of the large intestine which empties into the rectum),
most diverticulitis also takes place in the sigmoid. The
elderly have the most serious complications from
diverticulitis, although very severe infections can also
occur in patients under the age of 50. Men are three
times as likely as women to be stricken with
diverticulitis.
Diverticulitis is believed to occur when a hardened
piece of stool, undigested food, and bacteria (called a
fecalith) becomes lodged in a diverticulum. This
blockage interferes with the blood supply to the area,
and infection sets in.
An individual with diverticulitis will experience
pain (especially in the lower left side of the abdomen)
and fever. In response to the infection and the irritation of nearby tissues within the abdomen, the abdominal muscles may begin to spasm. About 25% of all
patients with diverticulitis will have some rectal bleeding, although this rarely becomes severe. Walled-off
pockets of infection, called abscesses, may appear
within the wall of the intestine, or even on the exterior
surface of the intestine. When a diverticulum weakens
sufficiently, and is filled to bulging with infected pus, a
perforation in the intestinal wall may develop. When
the infected contents of the intestine spill out into the
abdomen, the severe infection called peritonitis may
occur. Peritonitis is an infection and inflammation of
the lining of the abdominal cavity, the peritoneum.
Other complications of diverticulitis include the
formation of abnormal connections between two
organs that normally do not connect (fistulas; for
example, the intestine and the bladder), and scarring
outside of the intestine which squeezes off a portion of
the intestine, obstructing it.

Diagnosis
As mentioned, the majority of diverticula do not
cause any symptoms, and are often found by coincidence during an examination being performed for
some other medical condition.
When diverticula are suspected because a patient
begins to have sudden rectal bleeding, the location of
1199

Diverticulosis and diverticulitis

further back toward the beginning of the large intestine. The chance of developing diverticula increases
with age, so that by the age of 50, about 20–50% of
all people will have some diverticula. By the age of 90,
virtually everyone will have developed some diverticula. Most diverticula measure about 3 mm to just
over 3 cm in diameter. Larger diverticula, termed
giant diverticula, are quite infrequent, but may measure as large as 15 cm in diameter.

Diverticulosis and diverticulitis

Diagnosis of diverticulitis is not difficult in
patients with previously diagnosed diverticulosis.
The presence of abdominal pain and fever in such an
individual would make the suspicion of diverticulitis
quite high. Examination of the abdomen will usually
reveal tenderness to touch, with the patient’s abdominal muscles contracting strongly to protect the tender
area. During a rectal exam (performed by inserting a
finger into the rectum), a doctor may be able to feel
an abnormal mass. Touching this mass may prove
painful to the patient.
When a practitioner is suspicious of diverticulitis
as the cause for the patient’s symptoms, he or she will
most likely avoid the types of tests usually used
to diagnose gastrointestinal disorders. These include
barium enema and endoscopy. The concern is that the
increased pressure exerted on the intestine during
these exams may increase the likelihood of intestinal
perforation. After medical treatment for the diverticulitis, these examinations may be performed in order to
learn the extent of the patient’s disease.

Treatment

A barium study x ray showing colonic diverticulosis. (Custom
Medical Stock Photo. Reproduced by permission.)

the bleeding can be studied by performing an angiography. Angiography involves inserting a tiny tube
through an artery in the leg, and moving it up into
one of the major arteries of the gastrointestinal system. A particular chemical (contrast medium) which
will show up on x-ray films is injected, and the area of
bleeding is located by looking for an area where the
contrast is leaking into the interior (lumen) of the
intestine.
A procedure called endoscopy provides another
method for examining the colon and locating the site
of bleeding. In endoscopy, a small, flexible scope
(endoscope) is inserted through the rectum and into
the intestine. The scope usually bears a fiber-optic
camera, which allows the view through this endoscope
to be projected onto a television screen. The operator
can introduce the endoscope further and further
through the intestine to find the location of the
bleeding.
1200

Only about 20% of patients with diverticulosis
ever have symptoms which lead them to seek medical
help. Most people never know that they have diverticula. For those individuals who have cramping pain
and constipation believed to be due to diverticulosis,
the usual prescription involves increasing the fiber in
the diet. This can be done by adding special diet supplements of bran or psyllium seed, which increase
stool volume. Bleeding diverticula can usually be treated by bed rest, with blood transfusion needed for more
severe bleeding (hemorrhaging). In cases of very heavy
hemorrhaging, medications which encourage clotting
can be injected during the course of a diagnostic
angiography.
While there are almost no situations when uncomplicated diverticulosis requires surgery, giant diverticula always require removal. This is due to the very
high chance of infection and perforation of these
diverticula. When giant diverticula are diagnosed,
the usual treatment involves removing that portion
of the intestine.
Treatment for uncomplicated diverticulitis
usually requires hospitalization. ‘‘Resting the bowel’’
is a mainstay of treatment, and involves keeping the
patient from eating or sometimes even drinking anything by mouth. Therefore, the patient will need to
receive fluids through a needle in the vein (intravenous
or IV fluids). Antibiotics will also be administered
through the IV. Some physicians will agree to try
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Angiography—An x-ray study of the arteries in a
particular part of the body. Angiography is often
performed in order to localize internal bleeding.
Bowel obstruction—A blockage in the intestine
which prevents the normal flow of waste down
the length of the intestine.

The various complications of diverticulitis need to
be treated aggressively, because the death rate from
such things as perforation and peritonitis is quite high.
Abscesses can be drained of their infected contents by
inserting a needle through the skin of the abdomen
and into the abscess. When this is unsuccessful, open
abdominal surgery will be required to remove the piece
of the intestine containing the abscess. Fistulas require
surgical repair, including the removal of the length of
intestine containing the origin of the fistula, followed
by immediate reconnection of the two free ends of
intestine. Peritonitis requires open surgery. The entire
abdominal cavity is cleaned by being irrigated
(washed) with a warmed sterile saltwater solution,
and the damaged piece of intestine is removed.
Obstructions require immediate surgery to prevent
perforation. Massive, uncontrollable bleeding, while
rare, may require removal of part or all of the large
intestine.
During any of these types of operations, the surgeon must make an important decision regarding the
quantity of intestine which must be removed. When the
amount of intestine removed is great, it may be necessary to perform a colostomy. A colostomy involves pulling the end of the remaining intestine through the
abdominal wall, to the outside. This bit of intestine is
then fashioned so that a bag can be fit over it. The
patient’s waste (feces) collect in the bag, because the
intestine no longer connects with the rectum. This
colostomy may be temporary, in which case another
operation will be required to reconnect the intestine,
after some months of substantial healing has occurred.
Other times, the colostomy will need to be permanent,
and the patient will have to adjust to living permanently
with the colostomy bag. Most people with colostomies
are able to go on with a very active life.
Occasionally, a patient will have such severe
diverticular disease that a surgeon recommends planning ahead, and schedules removal of a portion of the
colon. This is done to avoid the high risk of surgery
performed after a complication has set in. Certain
developments in a patient will identify those patients
who are at very high risk of experiencing dangerous
complications. Such elective surgery may be
recommended:


when an older individual has had several attacks of
diverticulitis



when someone under the age of 50 has had even one
attack

GALE ENCYCLOPEDIA OF MEDICINE

Colostomy—A procedure performed when a large
quantity of intestine is removed. The end piece of
the intestine leading to the rectum is closed.
Diverticula—Outpouchings in the large intestine
caused when the inner, lining layer of the large
intestine (colon) bulges out (herniates) through the
outer, muscular layer.
Endoscopy—Examination of an area of the gastrointestinal tract by putting a lighted scope, usually
bearing a fiber-optic camera, into the rectum, and
passing it through the intestine.
Fistula—An abnormal connection formed between
two organs that usually have no connection
whatsoever.
Sigmoid colon—The final portion of the large intestine that empties into the rectum.



when treatment does not get rid of a painful mass



when the intestine appears to be narrowing on x-ray
examination (this could suggest the presence of
cancer)



when certain patients begin to regularly experience
painful urination or urinary infections (this suggests
that there may be a connection between the intestine
and the bladder)



when there is any question of cancer



when the diverticular disease appears to be progressing rapidly

Prognosis
The prognosis for people with diverticula is excellent, with only 20% of such patients ever seeking any
medical help for their condition.
While diverticulitis can be a difficult and painful
disease, it is usually quite treatable. Prognosis is worse
for individuals who have other medical problems,
particularly those requiring the use of steroid medications, which increase the chances of developing a
serious infection. Prognosis is also worse in the elderly.
1201

Diverticulosis and diverticulitis

treatment at home for very mildly ill patients. These
patients will be put on a liquid diet and receive oral
antibiotics.

Dizziness

Prevention
While there is no absolutely certain way to prevent
the development of diverticula, it is believed that highfiber diets are of help. Foods that are recommended
for their high fiber content include whole grain breads
and cereals, and all types of fruits and vegetables.
Most experts suggest that individuals take in about
0.71–1.23 oz (20–35) gs of fiber daily. If this is not
possible to achieve through a person’s diet, there are
fiber products which can be mixed into 8 oz (237l)
of water or juice, and which provide about 0.13–19
oz (4–6 gs) of fiber.
Resources
ORGANIZATIONS

National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.

Rosalyn Carson-DeWitt, MD

I Dizziness
Definition
As a disorder, dizziness is classified into three
categories–vertigo, syncope, and nonsyncope nonvertigo. Each category has a characteristic set of symptoms, all related to the sense of balance. In general,
syncope is defined by a brief loss of consciousness
(fainting) or by dimmed vision and feeling uncoordinated, confused, and lightheaded. Many people
experience a sensation like syncope when they stand
up too fast. Vertigo is the feeling that either the individual or the surroundings are spinning. This sensation is like being on a spinning amusement park ride.
Individuals with nonsyncope nonvertigo dizziness feel
as though they cannot keep their balance. This feeling
may become worse with movement.

Description
The brain coordinates information from the eyes,
the inner ear, and the body’s senses to maintain balance. If any of these information sources is disrupted,
the brain may not be able to compensate. For example, people sometimes experience motion sickness
because the information from their body tells the
brain that they are sitting still, but information from
1202

the eyes indicates that they are moving. The messages
do not correspond and dizziness results.
Vision and the body’s senses are the most important systems for maintaining balance, but problems in
the inner ear are the most frequent cause of dizziness.
The inner ear, also called the vestibular system, contains fluid that helps fine tune the information the
brain receives from the eyes and the body. When
fluid volume or pressure in one inner ear changes,
information about balance is altered. The discrepancy
gives conflicting messages to the brain about balance
and induces dizziness.
Certain medical conditions can cause dizziness,
because they affect the systems that maintain balance.
For example, the inner ear is very sensitive to changes
in blood flow. Because medical conditions such as high
blood pressure or low blood sugar can affect blood
flow, these conditions are frequently accompanied by
dizziness. Circulation disorders are the most common
causes of dizziness. Other causes are head injury, ear
infection, allergies, and nervous system disorders.
Dizziness often disappears without treatment or
with treatment of the underlying problem, but it can
be long term or chronic. According to the National
Institutes of Health, 42% of Americans will seek medical help for dizziness at some point in their lives. The
costs may exceed a billion dollars and account for five
million doctor visits annually. Episodes of dizziness
increase with age. Among people aged 75 or older,
dizziness is the most frequent reason for seeing a
doctor.

Causes and symptoms
Careful attention to symptoms can help determine
the underlying cause of the dizziness. Underlying problems may be benign and easily treated or they may be
dangerous and in need of intensive therapy. Not all
cases of dizziness can be linked to a specific cause.
More than one type of dizziness can be experienced
at the same time and symptoms may be mixed.
Episodes of dizziness may last for a few seconds or
for days. The length of an episode is related to the
underlying cause.
The symptoms of syncope include dimmed vision,
loss of coordination, confusion, lightheadedness, and
sweating. These symptoms can lead to a brief loss of
consciousness or fainting. They are related to a
reduced flow of blood to the brain; they often occur
when a person is standing up and can be relieved by
sitting or lying down. Vertigo is characterized by a
sensation of spinning or turning, accompanied by
GALE ENCYCLOPEDIA OF MEDICINE

A person may experience dizziness for many reasons. Syncope is associated with low blood pressure,
heart problems, and disorders in the autonomic nervous system, the system of involuntary functions
such as breathing. Syncope may also arise from emotional distress, pain, and other reactions to outside
stressors. Nonsyncope nonvertigo dizziness may be
caused by rapid breathing, low blood sugar, or
migraine headache, as well as by more serious medical
conditions.
Vertigo is often associated with inner ear problems called vestibular disorders. A particularly
intense vestibular disorder, Méniére’s disease, interferes with the volume of fluid in the inner ear. This
disease, which affects approximately one in every
1,000 people, causes intermittent vertigo over the
course of weeks, months, or years. Méniére’s disease
is often accompanied by ringing or buzzing in the ear,
hearing loss, and a feeling that the ear is blocked.
Damage to the nerve that leads from the ear to the
brain can also cause vertigo. Such damage can result
from head injury or a tumor. An acoustic neuroma, for
example, is a benign tumor that wraps around the
nerve. Vertigo can also be caused by disorders of the
central nervous system and the cirulatory system, such
as hardening of the arteries (arteriosclerosis), stroke,
or multiple sclerosis.
Some medications cause changes in blood pressure or blood flow. These medications can cause dizziness in some people. Prescription medications carry
warnings of such side effects, but common drugs, such
as caffeine or nicotine, can also cause dizziness.
Certain antibiotics can damage the inner ear and
cause hearing loss and dizziness.
Diet may cause dizziness. The role of diet may be
direct, as through alcohol intake. It may be also be
indirect, as through arteriosclerosis caused by a highfat diet. Some people experience a slight dip in blood
sugar and mild dizziness if they miss a meal, but this
condition is rarely dangerous unless the person is
diabetic. Food sensitivities or allergies can also be a
cause of dizziness. Chronic conditions, such as heart
disease, and serious acute problems, such as seizures
and strokes, can cause dizziness. However, such
conditions usually exhibit other characteristic
symptoms.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
During the initial medical examination, an individual with dizziness should provide a detailed description of the type of dizziness experienced, when it
occurs, and how often each episode lasts. A diary of
symptoms may help track this information. Report
any symptoms that accompany the dizziness, such as
a ringing in the ear or nausea, any recent injury or
infection, and any medication taken.
Blood pressure, pulse, respiration, and body temperature are checked, and the ear, nose, and throat are
scrutinized. The sense of balance is assessed by moving
the individual’s head to various positions or by tilttable testing. In tilt-table testing, the person lies on a
table that can be shifted into different positions and
reports any dizziness that occurs.
Further tests may be indicated by the initial examination. Hearing tests help assess ear damage. X rays,
computed tomography scan (CT scan), and magnetic
resonance imaging (MRI) can pinpoint evidence of
nerve damage, tumor, or other structural problems.
If a vestibular disorder is suspected, a technique called
electronystagmography (ENG) may be used. ENG
measures the electrical impulses generated by eye
movements. Blood tests can determine diabetes, high
cholesterol, and other diseases. In some cases, a heart
evaluation may be useful. Despite thorough testing, an
underlying cause cannot always be determined.

Treatment
Treatment is determined by the underlying cause.
If an individual has a cold or influenza, a few days of
bed rest is usually adequate to resolve dizziness. Other
causes of dizziness, such as mild vestibular system
damage, may resolve without medical treatment.
If dizziness continues, drug therapy may prove
helpful. Because circulatory problems often cause dizziness, medication may be prescribed to control blood
pressure or to treat arteriosclerosis. Sedatives may be
useful to relieve the tension that can trigger or aggravate dizziness. Low blood sugar associated with diabetes sometimes causes dizziness and is treated by
controlling blood sugar levels. An individual may be
asked to avoid caffeine, nicotine, alcohol, and any
substances that cause allergic reactions. A low-salt
diet may also help some people.
When other measures have failed, surgery may be
suggested to relieve pressure on the inner ear. If the
dizziness is not treatable by drugs, surgery, or other
means, physical therapy may be used and the patient
may be taught coping mechanisms for the problem.
1203

Dizziness

nausea, vomiting, ringing in the ears, headache, or fatigue. An individual may have trouble walking, remaining coordinated, or keeping balance. Nonsyncope
nonvertigo dizziness is characterized by a feeling of
being off balance that becomes worse if the individual
tries moving or performing detail-intense tasks.

Dizziness

Alternative treatment
Because dizziness may arise from serious conditions,
it is advisable to seek medical treatment. Alternative
treatments can often be used alongside conventional medicine without conflict. Relaxation techniques, such as
yoga and massage therapy that focus on relieving tension,
are popularly recommended methods for reducing stress.
Aromatherapists recommend a warm bath scented with
essential oils of lavender, geranium, and sandalwood.
Homeopathic therapies can work very effectively
for dizziness, and are especially applicable when no
organic cause can be identified. An osteopath or chiropractor may suggest adjustments of the head, jaw,
neck, and lower back to relieve pressure on the inner
ear. Acupuncturists also offer some treatment options
for acute and chronic cases of dizziness. Nutritionists
may be able to offer advice and guidance in choosing
dietary supplements, identifying foods to avoid, and
balancing nutritional needs.

Prognosis
Outcome depends on the cause of dizziness.
Controlling or curing the underlying factors usually
relieves dizziness. In some cases, dizziness disappears
without treatment. In a few cases, dizziness can
become a permanent disabling condition and a person’s options are limited.

Prevention
Most people learn through experience that certain
activities will make them dizzy and they learn to avoid
them. For example, if reading in a car produces motion
sickness, an individual leaves reading materials for
after the trip. Changes to the diet can also cut down
on episodes of dizziness in susceptible people.
Relaxation techniques can help ward off tension and
anxiety that can cause dizziness.
These techniques can help minimize or even prevent dizziness for people with chronic diseases. For
example, persons with Méniére’s disease may avoid
episodes of vertigo by leaving salt, alcohol, and caffeine
out of their diets. Reducing blood cholesterol can help
diminish arteriosclerosis and indirectly treat dizziness.
Some cases of dizziness cannot be prevented.
Acoustic neuromas, for example, are not predictable
or preventable. When the underlying cause of dizziness
cannot be discovered, it may be difficult to recommend
preventive measures. Alternative approaches designed
to rebalance the body’s energy flow, such as acupuncture and constitutional homeopathy, may be helpful in
cases where the cause of dizziness cannot be pinpointed.
1204

KEY TERMS
Acoustic neuroma—A benign tumor that grows on
the nerve leading from the inner ear to the brain. As
the tumor grows, it exerts pressure on the inner ear
and causes severe vertigo.
Arteriosclerosis—Hardening of the arteries caused
by high blood cholesterol and high blood pressure.
Autonomic nervous system—The part of the nervous system that controls involuntary functions
such as breathing and heart beat.
Computed tomography (CT)—An imaging technique in which cross-sectional x rays of the body are
compiled to create a three-dimensional image of
the body’s internal structures.
Electronystagmography—A method for measuring
the electricity generated by eye movements.
Electrodes are placed on the skin around the eye
and the individual is subjected to a variety of stimuli so that the quality of eye movements can be
assessed.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Vestibular system—The area of the inner ear that
helps maintain balance.

Resources
ORGANIZATIONS

Méniére’s Network. 1817 Patterson St., Nashville, TN
37203. (800) 545-4327. <http://
www.earfoundation.org>.
Vestibular Disorders Association. PO Box 4467, Portland,
OR 97208-4467. (503) 229-7705. <http://www.
teleport.com/~veda>.

Julia Barrett

DKA see Diabetic ketoacidosis
DLE see Discoid lupus erythematosus
Domestic violence see Abuse
Donovanosis see Granuloma inguinale
Doppler echocardiography see
Echocardiography
GALE ENCYCLOPEDIA OF MEDICINE

Doppler ultrasonography
Definition
Doppler ultrasonography is a non-invasive diagnostic procedure that changes sound waves into an
image that can be viewed on a monitor.

Purpose

Normal results

Ultrasound doppler
transducer

Carotid artery

No aftercare is necessary.

Aftercare

There is no special preparation needed for this
test. The ultrasound technician may apply a clear gel
to the skin in order to help the transducer more freely
over the body.

Preparation

During a Doppler ultrasonography procedure the
technician will apply a gel to the skin, then place
the transducer against the skin at various angles. The
transducer sends the information it receives to a television monitor that shows a moving image of the
organ being studied. The technician can save these
images either on video tape, paper, or x-ray film for
further study.

Doppler ultrasonography can detect the direction, velocity,
and turbulence of blood flow. Because it is non-invasive and
uses no x rays, doppler ultrasonography is widely used for
numerous diagnostic procedures. (Illustration by Electronic
Illustrators Group.)

rµe1 ,)

A Doppler ultrasonography test showing no
restricted blood flow is a normal finding.
1205

Doppler ultrasonography

Doppler ultrasonography can detect the direction,
velocity, and turbulence of blood flow. It is frequently
used to detect problems with heart valves or to measure blood flow through the arteries. Specifically, it is
useful in the work up of stroke patients, in assessing
blood flow in the abdomen or legs, and in viewing the
heart to monitor carotid artery diseases.

Precautions
The test is widely used because it is noninvasive,
uses no x rays, and gives excellent images. It is harmless, painless, and widely available.

Description
Doppler ultrasonography makes use of two different principles. The ultrasound principle is this:
when a high-frequency sound is produced and aimed
at a target, it will be reflected by its target and the
reflected sound can be detected back at its origin. In
addition, it is known that certain crystals (called piezoelectric crystals) produce an electrical pulse when
vibrated by a returning sound.
The Doppler principle is simply that sound pitch
increases as the source moves toward the listener and
decreases as it moves away.
Medical science utilizes these two principles in the
following way. A transducer (sometimes called a
probe) containing piezoelectric crystals sends a series
of short sound pulses into the body and pauses
between each pulse to listen for the returning sounds.
The machine then determines the direction and depth
of each returning sound and coverts this into a point of
light on a television monitor. Thousands of these
pulses are computed and displayed every second to
produce an image of the organ being studied. The
image allows the doctor to see the organ functioning
in real time.
The newest addition to this test is the addition of
color. Adding color to the image shows the direction
and rate of blood flow more clearly.
GALE ENCYCLOPEDIA OF MEDICINE

~t,)
\, 5

Down syndrome

KEY TERMS
Doppler effect—The principle that the sound of an
object moving toward you has a higher pitch than
the sound when it is moving away from you.
Transducer—The part of a machine that changes
signals in one form into another form.
Ultrasound—Sound that is too high for the human
ear to hear.

Abnormal results
Disrupted or obstructed blood flow through
the neck arteries may indicate the person is a risk of
having a stroke. (Narrowed arterial flow in the legs
does not necessarily indicate a risk of stroke.)
Resources
BOOKS

Samuels, Martin, and Steven Feske, editors. Office Practice
of Neurology. New York: Churchill Livingstone, 1996.

Dorothy Elinor Stonely

I Down syndrome
Definition
Down syndrome (DS) is the most common cause
of mental retardation and malformation in a newborn.
It occurs because of the presence of an extra chromosome. It was first described in 1866 by Dr. John L. H.
Down (1828–1896), an English physician.
Down syndrome occurs about once in every 800
births. It is estimated that about 6,000 children are
born with DS each year in the United States.

Description
Chromosomes are the units of genetic information that exist within every cell of the body. Twentythree distinctive pairs, or 46 total chromosomes, are
located within the nucleus (central structure) of each
cell. When a baby is conceived by the combining of
one sperm cell with one egg cell, the baby receives
23 chromosomes from each parent, for a total of
46 chromosomes. Sometimes, an accident in the production of a sperm or egg cell causes that cell to
1206

contain 24 chromosomes. This event is referred to as
nondisjunction. When this defective cell is involved in
the conception of a baby, that baby will have a total of
47 chromosomes. The extra chromosome in Down
syndrome is labeled number 21. For this reason, the
existence of three such chromosomes is sometimes
referred to as trisomy 21.
In a very rare number of Down syndrome cases
(about 1–2%), the original egg and sperm cells are
completely normal. The problem occurs sometime
shortly after fertilization; during the phase where
cells are dividing rapidly. One cell divides abnormally,
creating a line of cells with an extra chromosome 21.
This form of genetic disorder is called a mosaic. The
individual with this type of Down syndrome has two
types of cells: those with 46 chromosomes (the normal
number), and those with 47 chromosomes (as occurs
in Down syndrome). Some researchers have suggested
that individuals with this type of mosaic form of Down
syndrome have less severe signs and symptoms of the
disorder.
Another relatively rare genetic accident which can
cause Down syndrome is called translocation. During
cell division, the number 21 chromosome somehow
breaks. A piece of the 21 chromosome then becomes
attached to another chromosome. Each cell still has
46 chromosomes, but the extra piece of chromosome
21 results in the signs and symptoms of Down syndrome. Translocations occur in about 3–4% of cases
of Down syndrome.
Down syndrome occurs in about one in every
800–1,000 births. It affects an equal number of boys
and girls. Less than 25% of Down syndrome cases
occur due to an extra chromosome in the sperm cell.
The majority of cases of Down syndrome occur due to
an extra chromosome 21 within the egg cell supplied
by the mother (nondisjunction). As a woman’s age
(maternal age) increases, the risk of having a Down
syndrome baby increases significantly. For example,
at younger ages, the risk is about one in 4,000. By the
time the woman is age 35, the risk increases to one in
400; by age 40 the risk increases to one in 110; and by
age 45 the risk becomes one in 35. There is no
increased risk of either mosaicism or translocation
with increased maternal age.
Down syndrome sometimes occurs together with
such other developmental disorders as Rett syndrome.
Although such double diagnoses are very rare, it is
important for parents to recognize that the presence
of one chromosomal abnormality does not exclude
the possibility that their child may have a second
anomaly.
GALE ENCYCLOPEDIA OF MEDICINE

While Down syndrome is a chromosomal disorder,
a baby is usually identified at birth through observation
of a set of common physical characteristics. Babies with
Down syndrome tend to be overly quiet, less responsive, with weak, floppy muscles. Furthermore, a number of physical signs may be present. These include:


flat appearing face



small head



flat bridge of the nose



smaller than normal, low-set nose



small mouth, which causes the tongue to stick out
and to appear overly large



upward slanting eyes



extra folds of skin located at the inside corner of each
eye, near the nose (called epicanthal folds)



rounded cheeks



small, misshapen ears



small, wide hands



an unusual, deep crease across the center of the palm
(called a simian crease)



a malformed fifth finger



a wide space between the big and the second toes



unusual creases on the soles of the feet



overly-flexible joints (sometimes referred to as being
double-jointed)



shorter than normal height

Other types of defects often accompany Down
syndrome. About 30–50% of all children with Down
syndrome are found to have heart defects. A number
of different heart defects are common in Down
syndrome, including abnormal openings (holes) in
the walls that separate the heart’s chambers (atrial
septal defect, ventricular septal defect). These result
in abnormal patterns of blood flow within the heart.
The abnormal blood flow often means that less oxygen
is sent into circulation throughout the body. Another
heart defect that occurs in Down syndrome is called
Tetralogy of Fallot. Tetralogy of Fallot consists of
a hole in the heart, along with three other major
heart defects.
Malformations of the gastrointestinal tract are
present in about 5–7% of children with Down syndrome. The most common malformation is a narrowed, obstructed duodenum (the part of the
intestine into which the stomach empties). This disorder, called duodenal atresia, interferes with the baby’s
GALE ENCYCLOPEDIA OF MEDICINE

milk or formula leaving the stomach and entering the
intestine for digestion. The baby often vomits forcibly
after feeding, and cannot gain weight appropriately
until the defect is repaired.
Other medical conditions that occur in patients
with Down syndrome include an increased chance of
developing infections, especially ear infections and
pneumonia; certain kidney disorders; thyroid disease
(especially low or hypothyroid); hearing loss; vision
impairment requiring glasses (corrective lenses); and
a 20-times greater chance of developing leukemia
(a blood disorder).
Development in a baby and child with Down
syndrome occurs at a much slower than normal rate.
Because of weak, floppy muscles (hypotonia), babies
learn to sit up, crawl, and walk much later than their
normal peers. Talking is also quite delayed. The level
of mental retardation is considered to be mild-tomoderate in Down syndrome. The actual IQ range of
Down syndrome children is quite varied, but the
majority of such children are in what is sometimes
known as the trainable range. This means that most
people with Down syndrome can be trained to do
regular self-care tasks, function in a socially appropriate manner in a normal home environment, and even
hold simple jobs.
As people with Down syndrome age, they face an
increased chance of developing the brain disease called
Alzheimer’s (sometimes referred to as dementia or senility). Most people have a six in 100 risk of developing
Alzheimer’s, but people with Down syndrome have a
25 in 100 chance of the disease. In addition to an
increased risk of developing Alzheimer’s, patients with
DS show the first signs of the disease much earlier than
most people, often in their early 40s. Alzheimer’s disease causes the brain to shrink and to break down. The
number of brain cells decreases, and abnormal deposits
and structural rearrangements occur. This process
results in a loss of brain functioning. People with
Alzheimer’s have strikingly faulty memories. Over
time, people with Alzheimer’s disease will lapse into an
increasingly unresponsive state. Some researchers have
shown that even Down syndrome patients who do not
appear to have Alzheimer’s disease have the same
changes occurring to the structures and cells of their
brains. A new questionnaire was published in 2004 to
help doctors evaluate adults with Down syndrome for
symptoms of Alzheimer’s-related dementia.
As people with Down syndrome age, they also
have an increased chance of developing a number of
other illnesses, including cataracts, thyroid problems,
diabetes, and seizure disorders.
1207

Down syndrome

Causes and symptoms

Down syndrome

Diagnosis
Diagnosis is usually suspected at birth, when the
characteristic physical signs of Down syndrome are
noted. Once this suspicion has been raised, genetic
testing (chromosome analysis) can be undertaken in
order to verify the presence of the disorder. This testing is usually done on a blood sample, although chromosome analysis can also be done on other types of
tissue, including skin. The cells to be studied are prepared in a laboratory. Chemical stain is added to make
the characteristics of the cells and the chromosomes
stand out. Chemicals are added to prompt the cells to
go through normal development, up to the point
where the chromosomes are most visible, prior to cell
division. At this point, they are examined under a
microscope and photographed. The photograph is
used to sort the different sizes and shapes of chromosomes into pairs. In most cases of Down syndrome,
one extra chromosome 21 will be revealed. The final
result of such testing, with the photographed chromosomes paired and organized by shape and size, is called
the individual’s karyotype.

Treatment
No treatment is available to cure Down syndrome.
Treatment is directed at addressing the individual concerns of a particular patient. For example, heart defects
will many times require surgical repair, as will duodenal atresia. Many Down syndrome patients will need to
wear glasses to correct vision. Patients with hearing
impairment benefit from hearing aids.
A drug known as piracetam received some attention in the treatment of Down syndrome patients in
the mid-1990s. Piracetam is a so-called ‘‘smart drug’’
that is marketed in Europe and Japan to normal adults
hoping to increase their cognitive abilities. It is also
sold to skiers and mountain climbers as a remedy for
loss of concentration at high altitudes. Although some
European researchers have studied piracetam as a
possible treatment for dementia in Alzheimer’s disease, none of these trials have shown as of 2004 that
the drug is of any benefit to Alzheimer’s patients.
Piracetam is not approved for use in the United
States; several large shipments of it were seized by
the Food and Drug Administration in 2004.
Piracetam can be obtained via the Internet but is not
recommended by mainstream medical practitioners.
In 1998 the European company licensed to produce piracetam, UCB Pharma in Belgium, issued a
statement discouraging its use in children with Down
syndrome. The company obtained orphan drug status
for piracetam from the FDA in the early 2000s and has
1208

conducted a controlled trial of the drug as a possible
treatment for muscle spasms (myoclonus) in children.
While some decades ago, all Down syndrome children were quickly placed into institutions for lifelong
care. Research shows very clearly that the best outlook
for children with Down syndrome is a normal family
life in their own home. This approach, however,
requires careful support and education of the parents
and the siblings. It is a life-changing event to learn that
a new baby has a permanent condition that will effect
essentially all aspects of his or her development. Some
community groups exist to help families deal with the
emotional effects of this new information, and to help
plan for the baby’s future. Schools are required to
provide services for children with Down syndrome,
sometimes in separate special education classrooms,
and sometimes in regular classrooms. This educational practice is called mainstreaming or inclusion.

Prognosis
The prognosis in Down syndrome is quite variable, depending on the types of complications (heart
defects, susceptibility to infections, development of
leukemia) of each individual baby. The severity of
the retardation can also vary significantly. Without
the presence of heart defects, about 90% of children
with Down syndrome live into their teens. People with
Down syndrome appear to go through the normal
physical changes of aging more rapidly, however.
The average age of death for an individual with
Down syndrome is about 50–55 years. The most common cause of death is heart disease.
Still, the prognosis for a baby born with Down
syndrome in the early 2000s is better than ever before.
Because of modern medical treatments, including antibiotics to treat infections and surgery to treat heart
defects and duodenal atresia, life expectancy has greatly
increased. Community and family support allows people with Down syndrome to have rich, meaningful relationships. Because of educational programs, some
people with Down syndrome are able to hold jobs.
Men with Down syndrome appear to be uniformly sterile (meaning that they are unable to have
offspring). Women with Down syndrome, however,
are fully capable of having babies. About 50% of
these babies, however, will also be born with Down
syndrome.

Prevention
Efforts at prevention of Down syndrome are
aimed at genetic counseling of couples who are
GALE ENCYCLOPEDIA OF MEDICINE

Chromosome—The structures that carry genetic
information. Chromosomes are located within
every cell, and are responsible for directing the
development and functioning of all the cells in the
body. The normal number is 46 (23 pairs).
Karyotype—The specific chromosomal makeup of
a particular cell.
Mental retardation—A condition where an individual has a lower-than-normal IQ, and thus is developmentally delayed.
Mosaic—A term referring to a genetic situation, in
which an individual’s cells do not have the exact
same composition of chromosomes. In Down syndrome, this may mean that some of the individual’s
cells have a normal 46 chromosomes, while other
cells have an abnormal 47 chromosomes.
Nondisjunction—A genetic term referring to an
event which takes place during cell division, in
which a genetic accident causes an egg or sperm
cell to have 24 chromosomes, rather than the
normal 23.
Orphan drug—A term for a drug that treats a rare
disease, defined by the Food and Drug
Administration (FDA) as one that affects fewer
than 200,000 Americans. The FDA has an Office
of Orphan Products Development (OOPD), which
offers grants to researchers to develop these
products.
Translocation—A genetic term referring to a situation during cell division in which a piece of one
chromosome breaks off and sticks to another
chromosome.
Trisomy—The condition of having three identical
chromosomes instead of the normal two.

disorders. Carrying a baby with Down syndrome
often causes AFP to be lower than normal. This information alone, or along with measurements of two
other hormones, is considered along with the mother’s
age to calculate the risk of the baby being born with
Down syndrome. These results are only predictions,
and are only correct about 60% of the time.
The only way to definitively establish (with about
98–99% accuracy) the presence or absence of Down
syndrome in a developing baby, is to test tissue from
the pregnancy itself. This is usually done either by
amniocentesis or chorionic villus sampling (CVS). In
amniocentesis, a small amount of the fluid in which
the baby is floating is withdrawn with a long, thin
needle. In chorionic villus sampling, a tiny tube is
inserted into the opening of the uterus to retrieve a
small sample of the placenta (the organ that attaches
the growing baby to the mother via the umbilical cord,
and provides oxygen and nutrition). Both amniocentesis and CVS allow the baby’s own karyotype to be
determined. A couple must then decide whether to use
this information in order to begin to prepare for the
arrival of a baby with Down syndrome, or to terminate the pregnancy.
Once a couple has had one baby with Down syndrome, they are often concerned about the likelihood
of future offspring also being born with the disorder.
Most research indicates that this chance remains the
same as for any woman at a similar age. However,
when the baby with Down syndrome has the type that
results from a translocation, it is possible that one of
the two parents is a carrier of that defect. A carrier
conveys the genetic defect to the next generation but
does not actually have the disorder. When one parent
is a carrier of a translocation, the chance of future
offspring having Down syndrome is greatly increased.
The specific risk requires evaluation by a genetic
counselor.
Resources

preparing to have babies. A counselor needs to inform
a woman that her risk of having a baby with Down
syndrome increases with her increasing age. Two types
of testing is available during a pregnancy to determine
if the baby being carried has Down syndrome.
Screening tests are used to estimate the chance
that an individual woman will have a baby with
Down syndrome. At 14–17 weeks of pregnancy,
measurements of a substance called AFP (alphafetoprotein) can be performed. AFP is normally
found circulating in the blood of a pregnant woman,
but may be unusually high or low with certain
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Congenital Anomalies.’’ Section 19, Chapter 261 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Tierney, Lawrence, et al. Current Medical Diagnosis and
Treatment. Los Altos, CA: Lange Medical Publications,
2001.
PERIODICALS

Chen, Harold, MD. ‘‘Down Syndrome.’’ eMedicine
December 6, 2004. <http://www.emedicine.com/med/
topic567.htm>.
1209

Down syndrome

KEY TERMS

Drug metabolism/interactions

Egan, J. F., P. A. Benn, C. M. Zelop, et al. ‘‘Down Syndrome
Births in the United States from 1989 to 2001.’’
American Journal of Obstetrics and Gynecology 191
(September 2004): 1044–1048.
Evans, J. G., G. Wilcock, and J. Birks. ‘‘Evidence-Based
Pharmacotherapy of Alzheimer’s Disease.’’
International Journal of Neuropsychopharmacology 7
(September 2004): 351–369.
Leonard, H., L. Weaving, P. Eastaugh, et al. ‘‘Trisomy 21
and Rett Syndrome: A Double Burden.’’ Journal of
Paediatrics and Child Health 40 (July 2004):
406–409.
Prasher, V., A. Farooq, and R. Holder. ‘‘The Adaptive
Behaviour Dementia Questionnaire (ABDQ):
Screening Questionnaire for Dementia in Alzheimer’s
Disease in Adults with Down Syndrome.’’ Research in
Developmental Disabilities 25 (July-August 2004):
385–397.
Tanner, Lindsey. ‘‘Study: Drug May Hurt Syndrome
Kids.’’Chicago: Associated Press April 12, 2001.
Tyler, C., and J. C. Edman. ‘‘Down Syndrome, Turner
Syndrome, and Klinefelter Syndrome: Primary Care
throughout the Life Span.’’ Primary Care 31
(September 2004): 627–648.
ORGANIZATIONS

National Down Syndrome Congress. 1605 Chantilly Drive,
Suite 250, Atlanta, GA 30324-3269. (800) 232-6372.
National Down Syndrome Society. 666 Broadway, 8th
Floor, New York, NY 10012-2317. (800) 221-4602.
<http://www.ndss.org>.
National Organization for Rare Disorders (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT
06813-1968. (203) 744-0100. Fax: (203) 798-2291.
<http://www.rarediseases.org>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888)
INFO-FDA. <http://www.fda.gov>.
OTHER

Food and Drug Administration (FDA). ‘‘Grants Awarded
by the OOPD Program.’’ <http://www.fda.gov/
orphan/grants/previous.htm>.
Food and Drug Administration (FDA). ‘‘Refusal Actions
by FDA as Recorded in OASIS for China (Mainland).
August 2004. ’’ <http://www.fda.gov/ora/oasis/1/
ora_oasis_c_cn.html>.
Leshin, Lem, MD. ‘‘Piracetam and Down Syndrome.’’
http://www.ds-health.com/piracet.html.

Kim A. Sharp, M.Ln.
Rebecca J. Frey, PhD

Down’s syndrome see Down syndrome
Doxazosin see Alpha1-adrenergic blockers
Doxepin see Antidepressants, tricyclic
Doxycycline see Tetracyclines
1210

Dracontiasis see Guinea worm infection
Dracunculiasis see Guinea worm infection
Drooping eyelid see Ptosis
Drowning see Near-drowning
Drug abuse see Substance abuse and
dependence
Drug addiction see Substance abuse and
dependence
Drug dependence see Substance abuse and
dependence

I Drug metabolism/interactions
Definition
Drug metabolism is the process by which the body
breaks down and converts medication into active
chemical substances.

Precautions
Drugs can interact with other drugs, foods, and
beverages. Interactions can lessen or magnify the
desired therapeutic effect of a drug, or may cause
unwanted or unexpected side effects. There are thousands of possible drug-to-drug and drug-to-food interactions, and many medications and supplements are
contraindicated (not recommended) under certain
conditions or in patients with specific diseases and
disorders. This is why it is imperative that patients
always keep their physician fully informed about
all drugs and dietary supplements (including herbal
remedies) they are taking.

Description
The primary site of drug metabolism is the liver,
the organ that plays a major role in metabolism, digestion, detoxification, and elimination of substances
from the body. Enzymes in the liver are responsible
for chemically changing drug components into
substances known as metabolites. Metabolites are
then bound to other substances for excretion through
the lungs, or bodily fluids such as saliva, sweat, breast
milk, and urine, or through reabsorption by the intestines. The primary mode of excretion is through the
kidneys.
GALE ENCYCLOPEDIA OF MEDICINE

Drug interactions can occur when one drug inhibits or induces a P-450 that acts on another drug. An
example is nicotine, a drug contained in tobacco, and
known to induce P-450s. Individuals with liver disease
(e.g., cirrhosis) may also have insufficient levels of
P-450 enzymes. As a result, the concentration of
drugs metabolized by these enzymes (e.g., amprenavir
and other protease inhibitors) remains high and can
build up to toxic levels in the bloodstream. In addition,
certain medications and foods, such as grapefruit
juice, can inactivate or lessen the metabolic activity
of P-450s. Changing the drug dosage can alleviate the
problem in some cases.
The metabolic rate can vary significantly from
person to person, and drug dosages that work quickly
and effectively in one individual may not work well for
another. Factors such as genetics, environment,
nutrition, and age also influence drug metabolism;
infants and elderly patients may have a reduced capacity to metabolize certain drugs, and may require
adjustments in dosage.

Causes and symptoms
Drugs that commonly interact with other medications include:


Diuretics. Diuretics such as hydrochlorothiazide can
reduce serum potassium and sodium electrolyte
levels when taken with digoxin and lithium,
respectively.



Monoamine oxidase inhibitors (MAOIs). MAOI
antidepressants can cause convulsions and other serious side effects when used with tricyclic antidepressants (e.g., Imipramine, Nortriptyline), selective
serotonin reuptake inhibitors (SSRIs), or sympathomimetic drugs (e.g., amphetamines).



Antibiotics. Antibiotics may reduce the efficiency of
oral contraceptives.



Metals. Medications containing metals, such as antacids with aluminum additives and iron supplements,
can reduce the absorption of tetracyclines and
fluoroquinolones.



Drugs that inhibit liver enzyme function. Drugs that
slow drug metabolism include ciprofloxacin,

GALE ENCYCLOPEDIA OF MEDICINE

erythromycin, fluoxetine, nefazodone, paroxetine,
and ritonavir. The therapeutic effect of other medications taken with these drugs may be amplified.
Warfarin, a blood thinner, should be used with
great caution in individuals taking these drugs.
Foods and beverages that may interact with drugs
include:


Grapefruit juice. Grapefruit juice inhibits the metabolism of many medications, including cyclosporine,
felodipine, nifedipine, nitrendipine, nisoldipine,
carbamazepine, triazolam, and midazolam.



Foods and beverages with tyramines. Red wine,
malted beers, smoked foods (e.g., fish and meats),
dried fruits, and aged cheeses may contain tyramines,
and can cause a severe and dangerous elevation in
blood pressure when taken with MAOI inhibitors
(a class of antidepressants).



Dairy products. Milk, cream, and other dairy products containing calcium can prevention the absorption of antibiotics such as tetracycline, doxycycline,
and ciprofloxacin when they are taken with the drug.
In addition, whole milk with vitamin D can cause
milk-alkali syndrome in patients taking aluminum
hydroxide antacids.



Caffeinated beverages. The caffeine contained in
coffee and colas can influence drug metabolism.



Alcohol. Alcohol is a central nervous system depressant, and should not be taken with other CNS
depressants (e.g., antipsychotics, antihistamines). In
addition, certain fermented beverages may contain
tyramines.

This list is not all-inclusive and individuals should
always let their doctor and pharmacist know when
they are taking other medications, herbal remedies,
or dietary supplements. Anyone who experiences a
serious reaction to a drug that is not consistent with
its product labeling should report the event to their
doctor and/or the MedWatch adverse event reporting
system of the United States Food and Drug
Administration (FDA).

Alternative treatment
The growing use of herbal supplements has also
increased the opportunity for adverse drug and herbal
interactions. In 2000, the FDA issued a warning on the
popular herb St. John’s wort (Hypericum perforatum).
The supplement was found to inhibit the effect of
indinavir, a protease inhibitor used in the treatment
of HIV. It may also affect the action of cyclosporine
and other protease inhibitors (e.g., amprenavir,
1211

Drug metabolism/interactions

The family of liver isoenzymes known as cytochrome P-450 are crucial to drug metabolism. These
enzymes (labeled CYP1A2, CYP2C9, CYP2C19,
CYP2D6, and CYP3A4) have a catabolic action on
substances, breaking them down into metabolites.
Consequently, they also act to lower the concentration
of medication in the bloodstream.

Drug metabolism/interactions

ritonavir). Further clinical studies are still necessary to
determine the full metabolic effects of the herb.
Other herbs which may interact with allopathic
medications include gingko bilboa, ginseng, and garlic, which may all heighten the blood thinning effect of
the anticoagulant warfarin. Because herbs are regulated by the FDA as dietary supplements, they do not
require the same extensive clinical trials and premarket testing as drugs do before they are cleared for sale
in the United States. As such, there is still much
to learn about the potential interactions and adverse
effects associated with herbal supplements.
Individuals who experience serious side effects from
dietary supplements should report them to FDA’s
MedWatch program.

Diagnosis
Drug interactions can be difficult to detect. In
some cases, adverse reactions may closely resemble
the symptoms of the disease or condition the medication was prescribed to treat. Patients who take a number of medications or self-treat with over-the-counter
drugs and/or herbal remedies may not be able to
determine which drug actually triggered the interaction. A 2001 study by University of Florida researchers found that less than half of the women
participating disclosed their use of herbal therapies
to their healthcare providers. In cases where a serious
drug or herb interaction occurs, withholding this
information can delay diagnosis and put the patient
at increased risk.

KEY TERMS
Catabolism—A process of metabolism that breaks
down complex substances into simple ones.
Cirrhosis—Liver disease characterized by the
widespread disruption of the normal liver structure
and function.
CNS depressant—Anything that depresses, or
slows, the sympathetic impulses of the central
nervous system (i.e., respiratory rate, heart rate).
Drug interaction—A chemical or physiological
reaction that can occur when two different drugs
are taken together.
Enzymes—Organic substances (proteins) composed of amino acids that trigger and regulate
chemical reactions in the body. There are over
700 identified human enzymes.
Liver—A solid organ located on the right in the
upper abdomen. It plays a major role in metabolism, digestion, detoxification, and elimination of
substances from the body.
Metabolism—The sum of all the physical and
chemical processes occurring in the body to organize and maintain life.
Metabolites—Substances produced by metabolism
or by a metabolic process.
Milk-alkali syndrome—Elevated blood calcium
levels and alkalosis caused by excessive intake of
milk and alkalis. Usually occurs in the treatment of
peptic ulcer.

Treatment
Treatment of a drug interaction is dependant on a
number of factors, including the medication(s) or supplements used and the medical history of the patient.
A dosage adjustment may reverse the effects of some
interactions. Serious or life-threatening interactions
will require more aggressive therapies.

Prevention
Patients with chronic health conditions, particularly those with liver disorders, should always
inform their healthcare professional before taking
any over-the-counter (OTC) medications or dietary
supplements. Because of the risk for a drug-to-drug
interaction, individuals should also let their doctor
know if they are taking drugs prescribed by other
physicians. Individuals should closely follow
instructions for use and package directions on
both prescription and over-the-counter drugs.
1212

Consulting with a pharmacist and/or physician
may be beneficial if package directions are unclear
to the patient.
As a rule, grapefruit juice should not be taken
with medication unless recommended by a doctor.
Patients taking MAOI inhibitors should always
check food and beverage labels to ensure tyramines
are not included, and should avoid all fermented
drinks.
Resources
BOOKS

Beers, Mark H., and Robert Berkow. The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
& Co., Inc., 2004.
Medical Economics Company. The Physicians Desk
Reference (PDR). 55th ed. Montvale, NJ: Medical
Economics Company, 2001.
GALE ENCYCLOPEDIA OF MEDICINE

Hardy, Mary L. ‘‘Herb-Drug Interactions: An EvidenceBased Table.’’ Internal Medicine Alert 23 (January 29,
2001): 1.
ORGANIZATIONS

United States Food and Drug Administration (FDA).
MedWatch Adverse Events Reporting Program. 5600
Fishers Lane, Rockville, MD 20852-9787. 800-FDA1088. <http://www.fda.gov/medwatch/>.

Paula Anne Ford-Martin

I Drug overdose
Definition
A drug overdose is the accidental or intentional
use of a drug or medicine in an amount that is higher
than is normally used.

Description
All drugs have the potential to be misused,
whether legally prescribed by a doctor, purchased
over-the-counter at the local drug store, or bought
illegally on the street. Taken in combination with
other drugs or with alcohol, even drugs normally considered safe can cause death or serious long term consequences. Children are particularly at risk for
accidental overdose, accounting for over one million
poisonings each year from drugs, alcohol, and other
chemicals and toxic substances. People who suffer
from depression and who have suicidal thoughts are
also at high risk for drug overdose.

Causes and symptoms
Accidental drug overdose may be the result of
misuse of prescription medicines or commonly used
medications like pain relievers and cold remedies.
Symptoms differ depending on the drug taken. Some
of the drugs commonly involved in overdoses are listed
below along with symptoms and outcomes.
Acetaminophen is the generic name for the commonly used pain reliever Tylenol. Overdose of this
drug causes liver damage with symptoms that include
loss of appetite, tiredness, nausea and vomiting, paleness, and sweating. The next stage of symptoms indicates liver failure and includes abdominal pain and
tenderness, swelling of the liver, and abnormal blood
tests for liver enzymes. In the last stage of this
GALE ENCYCLOPEDIA OF MEDICINE

poisoning, liver failure advances and the patient
becomes jaundiced, with yellowing of the skin and
whites of the eyes. They may also experience kidney
failure, bleeding disorders, and encephalopathy (swelling of the brain).
Anticholinergic drugs (drugs that block the action
of acetylcholine, a neurotransmitter) like atropine,
scopolamine, belladonna, antihistamines, and antipsychotic agents cause the skin and moist tissues (like in
the mouth and nose) to become dry and flushed.
Dilated pupils, an inability to urinate, and mental
disturbances are also symptoms. Severe toxicity can
lead to seizures, abnormal heart rhythms, extremely
high blood pressure, and coma.
Antidepressant drugs like amitriptyline, desipramine, and nortriptyline can cause irregular heart
rate, vomiting, low blood pressure, confusion, and
seizures. An overdose of antidepressants also causes
symptoms similar to those seen with anticholinergic
drug overdoses.
Cholinergic drugs (drugs that stimulate the parasympathetic nervous system) like carbamate and pilocarpine cause nausea, diarrhea, increased secretion of
body fluids (sweat, tears, saliva, and urine), fatigue,
and muscle weakness. Convulsions are possible.
Death can occur due to respiratory failure and heart
failure.
Cocaine and crack cocaine overdoses cause seizures, high blood pressure, increased heart rate, paranoia, and other changes in behavior. Heart attack or
stroke are serious risks within three days after cocaine
overdose.
Depressant drugs (tranquilizers, antianxiety
drugs, sleeping pills) cause sleepiness, slowed or
slurred speech, difficulty walking or standing, blurred
vision, impaired ability to think, disorientation, and
mood changes. Overdose symptoms can include
slowed breathing, very low blood pressure, stupor,
coma, shock, and death.
Digoxin, a drug used to regulate the heart, can
cause irregular heart beats, nausea, confusion, loss of
appetite, and blurred vision.
Narcotics or opiates are drugs like heroin, morphine, and codeine. Clonidine and diphenoxylate
(Lomotil) are also in this category. Overdose with
opiate drugs causes sedation (sleepiness), low blood
pressure, slowed heart rate, and slowed breathing.
Pinpoint pupils, where the black centers of the eyes
become smaller than normal, are common in opiate
overdose. However, if other drugs are taken at the
same time as the opiates, they may counteract this
1213

Drug overdose

PERIODICALS

Drug overdose

effect on the pupils. A serious risk is that the patient
will stop breathing.
Salicylates are found in aspirin and some creams
or ointments used for muscle and joint pain (like BenGay), and creams for psoriasis, a skin condition. Initial
symptoms are gastrointestinal irritation, fever, and
vomiting, possibly with blood in the vomit. This overdose will cause metabolic acidosis and respiratory alkalosis, conditions where the body’s acid/base balance is
malfunctioning. Symptoms include rapid heart beat
and fast breathing. Nervous system symptoms include
confusion, hallucinations, tiredness, and ringing in the
ears. An increased tendency to bleed is also common.
Serious complications include acute renal failure,
coma, and heart failure. Acute salicylate poisoning
can lead to death.

Diagnosis

information as possible to the poison control center
can help determine what the next course of action
should be.
The poison control center, paramedics, and emergency room staff will want to know:


What drug(s) were taken try to locate the drug’s
container?



How much of the drug was taken?



When was the drug taken?



Was the drug taken with alcohol or any other drugs
or chemicals?



What is the age of the patient?



What symptoms are the patient experiencing?



Is the patient conscious?



Is the patient breathing?

Diagnosis of a drug overdose may be based on the
symptoms that develop, however, the drug may do
extensive damage to the body before significant symptoms develop. If the patient is conscious, he or she may
be able to tell what drugs were taken and in what
amounts. The patient’s recent medical and social history may also help in a diagnosis. For example, a list of
medications that the patient takes, whether or not
alcohol was consumed recently, even if the patient
has eaten in the last few hours before the overdose,
can be valuable in determining what was taken and
how fast it will be absorbed into the system.

The poison control center may recommend trying
to get the patient to vomit. A liquid called ipecac
syrup, which is used to induce vomiting, is available
from pharmacies without a prescription. Pediatricians
may recommend that families keep ipecac syrup on
hand in households with children. This medication
should be used only on the advice of a medical professional. Vomiting should not be induced if the patient is
unconscious.

Different drugs have varying effects on the body’s
acid/base balance and on certain elements in the blood
like potassium and calcium. Blood tests can be used to
detect changes in body chemistry that may give clues
to what drugs were taken. Blood can also be screened
for various drugs in the system. Once the overdose
drug is identified, blood tests can be used to monitor
how fast the drug is being cleared out of the body.
Urine tests can also be used to screen for some drugs
and to detect changes in the body’s chemistry. Blood
and urine tests may show if there is damage to the liver
or kidneys as a result of the overdose.

Emergency medical treatment may include:

Emergency care



Assessment of the patient’s airway and breathing to
making sure that the trachea, the passage to the
lungs, is not blocked. If needed, a tube may be
inserted through the mouth and into the trachea to
help the patient breath. This procedure is called
intubation.



Assessment of the patient’s heart rate, blood pressure, body temperature, and other physical signs that
might indicate the effects of the drug.



Blood and urine samples may be collected to test for
the presence of the suspected overdose drug, and any
other drugs or alcohol that might be present.



Elimination of the drug that has not yet been
absorbed is attempted. Vomiting may be induced
using ipecac syrup or other drugs that cause vomiting. Ipecac syrup should not be given to patients who
overdosed with tricyclic antidepressants, theophylline, or any drug that causes a significant change in
mental status. If a patient vomits while unconscious,
there is a serious risk of choking.

Treatment
Immediate care
If a drug overdose is discovered or suspected, and
the person is unconscious, having convulsions, or is
not breathing, call for emergency help immediately. If
the person who took the drug is not having symptoms,
do not wait to see if symptoms develop; call a poison
control center immediately. Providing as much
1214

GALE ENCYCLOPEDIA OF MEDICINE



Gastric lavage, or washing out the stomach, may be
attempted. For this procedure a tube flexible tube is
inserted through the nose, down the throat, and into the
stomach. The contents of the stomach are then suctioned out through the tube. A solution of saline (salt
water) is injected into the tube to rinse out the stomach.
This solution is then suctioned out. This is the process
used when someone has his/her stomach pumped.
Activated charcoal is sometimes given to absorb the
drug.



Medication to stimulate urination or defecation may
be given to try to flush the excess drug out of the
body faster.



Intravenous (IV) fluids may be given. An intravenous
line, a needle inserted into a vein, may be put into the
arm or back of the hand. Fluids, either sterile saline (salt
water solution) or dextrose (sugar water solution), can
be administered through this line. Increasing fluids can
help to flush the drug out of the system and to reestablish balance of fluids and minerals in the body. The pH
(acid/base balance) of the body may need to be corrected by administering electrolytes like sodium, potassium, and bicarbonate through this IV line. If drugs
need to be administered quickly, they can also be
injected directly into the IV line.



Hemodialysis is a procedure where blood is circulated out of the body, pumped through a dialysis
machine, then reintroduced back into the body.
This process can be used to filter some drugs out of
the blood. It may also be used temporarily or long
term if the kidneys are damaged due to the overdose.



Antidotes are available for some drug overdoses. An
antidote is another drug that counteracts or blocks
the overdose drug. For example, acetaminophen
overdose can be treated with an oral medication,
N-acetylcysteine (Mucomyst), if the level of acetaminophen found in the blood is extremely high.
Naloxone is an anti-narcotic drug that is given to
counteract narcotic poisoning. Nalmefen or methadone may also be used.



KEY TERMS
Gastric lavage—Also called a stomach pump. For
this procedure, a flexible tube is inserted through
the nose, down the throat, and into the stomach
and the contents of the stomach are suctioned out.
The inside of the stomach is rinsed with a saline
(salt water) solution.
Intubation—A procedure where a tube is inserted
through the mouth and into the trachea keep the
airway open and to help the patient breathe.

care as a result of heart failure, stroke, or coma. Death
can occur in almost any drug overdose situation, particularly if treatment is not started immediately.

Prevention
To protect children from accidental drug overdose, all medications should be stored in containers
with child resistant caps. All drugs should be out of
sight and out of reach of children, preferably in a
locked cabinet. Prescription medications should be
used according to directions and only by the person
whose name is on the label. Threats of suicide need to
be taken seriously and appropriate help sought for
people with depression or other mental illness that
may lead to suicide.
Resources
OTHER

‘‘Drug Overdose.’’ American Institute of Preventative
Medicine. <http://www.healthy.net>.
Graber, Mark A., and Rhea Allen. ‘‘Emergency Medicine:
Overdose and Toxindromes.’’ University of Iowa Family
Practice Handbook. <http://www.vh.org/Providers/
ClinRef/FPHandbook/Chapter01/20-1.html>.

Altha Roberts Edgren

Psychiatric evaluation may be recommended if the
drug overdose was taken deliberately.

Prognosis
While many victims of drug overdose recover
without long term effects, there can be serious consequences. Some drug overdoses cause the failure of
major organs like the kidneys or liver, or failure of
whole systems like the respiratory or circulatory systems. Patients who survive drug overdose may need
kidney dialysis, kidney or liver transplant, or ongoing
GALE ENCYCLOPEDIA OF MEDICINE

I Drug therapy monitoring
Definition
Drug therapy monitoring, also known as
Therapeutic Drug Monitoring (TDM), is a means of
monitoring drug levels in the blood.
1215

Drug therapy monitoring



Drug therapy monitoring

Purpose
TDM is employed to measure blood drug levels
so that the most effective dosage can be determined,
with toxicity prevented. TDM is also utilized to
identify noncompliant patients (those patients
who, for whatever reason, either cannot or will not
comply with drug dosages as prescribed by the
physician).

Precautions
Because so many different factors influence
blood drug levels, the following points should be
taken into consideration during TDM: the age and
weight of the patient; the route of administration of
the drug; the drug’s absorption rate, excretion rate,
delivery rate, and dosage; other medications the
patient is taking; other diseases the patient has; the
patient’s compliance regarding the drug treatment
regimen; and the laboratory methods used to test
for the drug.

Description
TDM is a practical tool that can help the physician provide effective and safe drug therapy in
patients who need medication. Monitoring can be
used to confirm a blood drug concentration level
that is above or below the therapeutic range, or if
the desired therapeutic effect of the drug is not as
expected. If this is the case, and dosages beyond
normal then have to be prescribed, TDM can minimize the time that elapses.
TDM is important for patients who have other
diseases that can affect drug levels, or who take other
medicines that may affect drug levels by interacting
with the drug being tested. As an example, without
drug monitoring, the physician cannot be sure if a
patient’s lack of response to an antibiotic reflects
bacterial resistance, or is the result of failure to reach
the proper therapeutic range of antibiotic concentration in the blood. In cases of life-threatening infections, timing of effective antibiotic therapy is critical
to success. It is equally crucial to avoid toxicity in a
seriously ill patient. Therefore, if toxic symptoms
appear with standard dosages, TDM can be used to
determine changes in dosing.
Drawn blood, used for TDM, demonstrates a
drug action in the body at any specific time, whereas
drug levels examined from urine samples reflect the
presence of a drug over many days (depending on the
rate of excretion). Therefore, blood testing is the
procedure of choice when definite data are required.
1216

Therapeutic Drug Monitoring: Therapeutic And Toxic Range

Drug Level*

Use

Acetaminophen
mg/ml
Amikacin mg/
ml
Aminophylline ng/
ml
Amitriptyline ng/
ml
Carbamazepine
mg/ml
Chloramphenicol
mg/ml
Digoxin ng/ml
Gentamicin

Analgesic,
antipyretic
Antibiotic

Lidocaine

Therapeutic
Level*

Toxic

Bronchodilator

Depends on
use
12–25 mg/
ml**
10–20 mg/ml

>250

>20

Antidepressant

120–150 ng/ml

>500

Anticonvulsant

5–12 mg/ml

>12

Antibiotic

10–20 mg/ml

>25

Cardiotonic
Antibiotic

0.8–2.0 ng/ml
4–12 mg/L

Antiarrhythmic

1.5–5.0 mg/ml

>2.4
>12
mg/L
>5 mg/
ml
>2.0
>500

>25

Lithium mEq/L
Antimanic
0.7–2.0 mEq/L
Nortriptyline ng/
Antidepressant
50–150 ng/ml
ml
Phenobarbital mg/
Anticonvulsant
10–30 mg/ml
>40
ml
Phenytoin mg/ml
Anticonvulsant
7–20 mg/ml
>30
Procainamide mg/
Antiarrhythmic
4–8 mg/ml
>16
ml
Propranolol ng/ml
Antiarrhythmic
50–100 ng/ml
>150
Quinidine mg/ml
Antiarrhythmic
1–4 mg/ml
>10
Theophylline mg/
Bronchodilator
10–20 mg/ml
>20
ml
Tobramycin mg/
Antibiotic
4–12 mg/ml**
>12
ml
Valproic acid mg/
Anticonvulsant
50–100 mg/ml
>100
ml
*Values are laboratory-specific
**Concentration obtained 30 minutes after the end of a 30–minute infusion.

However, for adequate absorption and therapeutic
levels to be accurate, it is important to allow for
sufficient time to pass between the administration of
the medication and the collection of the blood
sample.
Blood specimens for drug monitoring can be
taken at two different times: during the drug’s highest
therapeutic concentration (‘‘peak’’ level), or its lowest
(‘‘trough’’ level). Occasionally called residual levels,
trough levels show sufficient therapeutic levels;
whereas peak levels show poisoning (toxicity). Peak
and trough levels should fall within the therapeutic
range.

Preparation
In preparing for this test, the following guidelines
should be observed:
GALE ENCYCLOPEDIA OF MEDICINE

Depending on the drug to be tested, the physician
should decide if the patient is to be fasting (nothing
to eat or drink for a specified period of hours) before
the test.



For patients suspected of symptoms of drug toxicity,
the best time to draw the blood specimen is when the
symptoms are occurring.



If there is a question as to whether an adequate dose
of the drug is being achieved, it is best to obtain
trough (lowest therapeutic concentration) levels.



Peak (highest concentration) levels are usually
obtained one to two hours after oral intake, approximately one hour after intramuscular (IM) administration (a shot in the muscle), and approximately
30 minutes after intravenous (IV) administration.
Residual, or trough, levels are usually obtained
within 15 minutes of the next scheduled dose.

Risks

Oxytocin also may be used to control bleeding
after delivery or to help make the milk flow in
women who are breastfeeding their babies.

Description
Oxytocin is a hormone and is available only with a
physician’s prescription. When used to start or continue labor, it is slowly injected into a vein. A nasal
spray form is used to increase milk flow in breastfeeding. Some commonly used brand names are Pitocin
and Syntocinon.

Recommended dosage
The dosages given here are average doses.
However, doses may be different for different patients.
Follow the orders of the physician who prescribed
the drug.
For increasing milk production:

Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting
or feeling lightheaded after blood is drawn, or accumulation of blood under the puncture site
(hematoma).

One spray into one or both nostrils, two–three
minutes before nursing or using a breast pump.
For starting or continuing labor:
The physician in charge will determine the appropriate dose.

Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

I Drugs used in labor
Definition
These drugs are used to induce (start) or continue
labor.

Purpose
The drug decribed here, oxytocin, makes the
uterus (womb) contract. Physicians use it to deliberately start labor. Because there are some risks with
using oxytocin, this should be done only when there
are good medical reasons. Any woman who is being
given oxytocin should make sure she has discussed the
benefits and risks with her physician.
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Oxytocin does not help increase or continue labor
in all patients. When it does not help, the physician
may deliver the baby by cesarean section.
In women who are especially sensitive to oxytocin,
the drug may cause contractions to become too strong.
This could tear the uterus or deprive the fetus of blood
and oxygen during labor.
Oxytocin does not help improve milk flow in all
women who are breastfeeding. Check with a physician
if the drug does not seem to be working.
Women with heart disease, high blood pressure,
or kidney disease should let their physicians know
about these conditions before taking oxytocin. Also,
anyone who has had an unusual reaction to oxytocin
in the past should inform their physician.

Side effects
Oxytocin has caused irregular heartbeat and
increased bleeding in some women after delivery. It
may also cause jaundice (yellowing of the eyes and
skin) in newborns.
1217

Drugs used in labor



Dry mouth

KEY TERMS
Cesarean section—The delivery of a baby through
a surgical procedure.
Fetus—A developing baby inside the womb.
Hormone—A substance that is produced in one
part of the body, then travels through the bloodstream to another part of the body where it has its
effect.

Other side effects are rare, but may include
nausea, vomiting, confusion, dizziness, convulsions,
breathing problems, headache, hives, skin rash, itching,
pelvic or abdominal pain, and weakness. The nasal
spray form may cause watery eyes or irritation of
the nose.

Interactions
Anyone who takes oxytocin should let the physician know all other medicines she is taking.
Nancy Ross-Flanigan

I Dry mouth
Definition
Dry mouth, known medically as xerostomia, is the
abnormal reduction of saliva due to medication,
disease, or medical therapy.

Description
Dry mouth due to the lack of saliva can be a
serious medical problem. Decreased salivation can
make swallowing difficult, can decrease taste sensation, and can promote tooth decay.

Causes and symptoms
Dry mouth, resulting from thickened or reduced
saliva flow, can be caused by a number of factors:
medications, both prescription and over-the-counter;
such systemic diseases as anemia, HIV infection, or
diabetes, manifestations of Sjögren’s syndrome
(as rheumatoid arthritis, lupus, chronic hardening
and thickening of the skin, or chronic and progressive
1218

inflammation of skeletal muscles); infections of the
salivary glands; blockage of the salivary ducts caused
by stones or tumors forming in the ducts through
which the saliva passes; dehydration; such medical
therapies as local surgery or radiation; secretion
reduction normally involved in the aging process;
and emotional stress.

Diagnosis
The diagnosis of dry mouth is not difficult. The
patient will state that his or her saliva is very thick or
nonexistent. Finding the cause of dry mouth may be
more difficult and require some laboratory testing.
Salivary gland biopsy for stones or tumors should be
performed if indicated.

Treatment
The treatment of dry mouth involves the management of the condition causing it. If dry mouth is
caused by medication, the medication should be changed. If dry mouth is caused by blockage of the salivary
ducts, the cause of the blockage should be investigated. When systemic diseases, such as diabetes and
anemia, are brought under control dry mouth
problems may decrease.
The use of caffeine-containing beverages, alcoholic beverages, and mouthwashes containing alcohol
should be minimized. The drinking of water and fruit
juices will decrease dry mouth problems. Chewing
gum and lemon drops can be used to stimulate saliva
flow. Bitters also can initiate salivary flow as long as
the salivary glands and ducts are functional.
Commercial saliva substitutes are available without
prescription and can be used as frequently as needed.
Use of a humidifier in the bedroom reduces nighttime
oral dryness.
Dry mouth caused by the aging process or radiation therapy for cancer can be treated by such oral
medications as pilocarpine (Salagen). Drugs that are
given to increase the flow of saliva are known as
sialogogues.

Prognosis
The prognosis for patients with xerostomia due
to medication problems is good, if the offending
agent can be changed. Dry mouth due to systemic
problems may be eliminated or improved once the
disease causing the dry mouth is under control.
Persistent xerostomia can be managed well with
saliva substitutes.
GALE ENCYCLOPEDIA OF MEDICINE

American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://www.amaassn.org>.

Salivary duct—Tube through which saliva is
carried from the salivary gland to the mouth.
Salivary gland—Gland in which saliva forms.
Sialogogue—A medication given to increase the
flow of saliva.
Xerostomia—The medical term for dry mouth.

Joseph Knight, PA
Rebecca J. Frey, PhD

Dry skin see Ichthyosis
Dual energy x-ray absorptiometry (DXA)
scan see Bone density test
DUB see Dysfunctional uterine bleeding

Prevention
A patient needs to ask his or her health care
provider if any medication to be prescribed will cause
dry mouth. Patients with persistent xerostomia need to
practice good oral hygiene and visit a dentist on a
regular basis; the lack of adequate saliva can cause
severe dental decay. The salivary glands are very sensitive to radiation, so any patient scheduled for radiation therapy of the head and neck needs to discuss with
the radiation therapist ways to minimize exposure of
the salivary glands to radiation.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Dentistry in Medicine.’’ Section 9, Chapter 103 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Bruce, S. D. ‘‘Radiation-Induced Xerostomia: How Dry Is
Your Patient?’’ Clinical Journal of Oncology Nursing 8
(February 2004): 61–67.
Nagler, R. M. ‘‘Salivary Glands and the Aging Process:
Mechanistic Aspects, Health-Status and Medicinal Efficacy Monitoring.’’ Biogerontology 5 (March 2004):
223–233.
Pinto, A., and S. S. De Rossi. ‘‘Salivary Gland Disease in
Pediatric HIV Patients: An Update.’’ Journal of
Dentistry for Children (Chicago) 71 (January-April
2004): 33–37.
Porter, S. R., C. Scully, and A. M. Hegarty. ‘‘An Update
of the Etiology and Management of Xerostomia.’’
Oral Surgery, Oral Medicine, Oral Pathology,
Oral Radiology, and Endodontics 97 (January 2004):
28–46.
ORGANIZATIONS

American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Duchenne muscular dystrophy see Muscular
dystrophy
Duodenal atresia see Duodenal obstruction

I Duodenal obstruction
Definition
Duodenal obstruction is a failure of food to pass
out of the stomach either from a complete or partial
obstruction.

Description
The duodenum is the first part of the intestine,
into which the stomach, the gall bladder, and the
pancreas empty their contents. The pylorus connects
the duodenum with the stomach and contains the
valve that regulates stomach emptying. Obstruction
usually occurs right at this outlet, so that the gall
bladder and pancreas are unable to drain their secretions without hindrance.

Causes and symptoms
Obstruction of the duodenum occurs in adults
and infants, each for a different set of reasons. In
adults, the usual cause is a peptic ulcer of such
antiquity that repeated cycles of injury and scarring have narrowed the passageway. Medical treatment of ulcers has progressed to the point where
such obstinate ulcer disease is rarely seen any
more. In infants, the conditions are congenital–
either the channel is underdeveloped or the pylorus
is overdeveloped. The first type is called duodenal
hypoplasia and the second is termed hypertrophic
pyloric stenosis. In rare cases, the channel
may be missing altogether, a condition called duodenal atresia. To say that these anomalies are
1219

Duodenal obstruction

KEY TERMS

Duodenal obstruction

congenital is not to say their cause is understood.
As with most birth defects, the specific cause is not
known.
Food that cannot exit the stomach in the forward
direction will return whence it came. Vomiting is the
constant symptom of duodenal obstruction. It may be
preceded by indigestion and nausea as the stomach
attempts to squeeze its contents through an ever
narrowing outlet.
Hypertrophic pyloric stenosis appears soon after
birth. The infant will vomit feedings, lose weight, and
be restless and irritable.

KEY TERMS
Atresia—Failure to develop; complete absence.
Contrast agent—A substance that produces shadows on an x ray so that hollow structures can be
more easily seen.
Gastroscopy—Looking into the stomach with a
flexible viewing instrument called a gastroscope.
Hypoplasia—Incomplete development.
Peptic ulcer—A wound in the lower stomach and
duodenum caused by stomach acid and a newly
discovered germ called Helicobacter pylori.

Diagnosis
X rays taken with contrast material in the stomach
readily demonstrate the site of the blockage and often
the ulcer that caused it. Gastroscopy is another way to
evaluate the problem. In infants, x rays may not be
necessary to detect pyloric stenosis. It is often possible
to feel the enlarged pylorus, like an olive, deep under
the ribs and see the stomach rippling as it labors to
force food through.

Treatment

advanced and continuous medical care available.
Achieving this desirable goal is the rule with surgery for duodenal obstructions of all types. The
bowel is so malleable that there is a rearrangement
to suit every occasion. The variety of possible configurations is limited only by the surgeon’s
imagination.

Prevention

Bowel obstruction requires a surgeon, sometimes
immediately. Newer surgical techniques constantly
improve the outcome, but obstruction is a mechanical
problem that needs a mechanical solution. Most
adults who come to surgery for obstruction have suffered for years from peptic ulcer disease. They will
usually benefit from ulcer surgery at the same time
their obstruction is relieved. The surgeon will therefore select a procedure that combines relief of obstruction with remedy for ulcer disease. There are many
choices. In fact, even without obstruction, functional
considerations require ulcer surgery to include
enhancement of stomach emptying.

Prompt and effective treatment of peptic ulcers
will prevent chronic scarring and narrowing. Drugs
developed over the past few decades have all but
eliminated the need for ulcer surgery.

To treat an infant with hypertrophic pyloric stenosis, some surgeons have had success with forceful
balloon dilation of the pylorus done through a gastroscope, but the standard procedure is to cut across the
overdeveloped circular muscle that is constricting the
stomach outlet. There are reports of infant hypertrophic pyloric stenosis remitting without surgery
following a very careful feeding schedule, but mortality is unacceptably high.

J. Ricker Polsdorfer, MD

Prognosis
A functioning and unrestricted intestine is a
prerequisite for living independent of the most
1220

Resources
BOOKS

Redel, Carol A., and R. Jeff Zeiwner. ‘‘Anatomy and
Anomalies of the Stomach and Duodenum.’’ In
Sleisenger & Fordtran’s Gastrointestinal and Liver
Disease, edited by Mark Feldman, et al. Philadelphia:
W. B. Saunders Co., 1997.

Duodenal stenosis see Duodenal obstruction
Duodenal ulcers see Ulcers (digestive)
Duodenum x rays see Hypotonic
duodenography
Duplicated ureter see Congenital ureter
anomalies
Dwarfism see Achondroplasia; Pituitary
dwarfism
GALE ENCYCLOPEDIA OF MEDICINE

I Dysentery
Definition
Dysentery is a general term for a group of gastrointestinal disorders characterized by inflammation of
the intestines, particularly the colon. Characteristic
features include abdominal pain and cramps, straining
at stool (tenesmus), and frequent passage of watery
diarrhea or stools containing blood and mucus. The
English word dysentery comes from two Greek words
meaning ‘‘ill’’ or ‘‘bad’’ and ‘‘intestine.’’

Causes
The most common types of dysentery and their
causal agents are as follows:


Bacillary dysentery. Bacillary dysentery, which is
also known as shigellosis, is caused by four species
of the genus Shigella: S. dysenteriae, the most virulent species and the one most likely to cause epidemics; S. sonnei, the mildest species and the most
common form of Shigella found in the United States;
S. boydii; and S. flexneri. S. flexneri is the species that
causes Reiter’s syndrome, a type of arthritis that
develops as a late complication of shigellosis.
About 15,000 cases of shigellosis are reported to the
CDC each year for the United States; however, the
CDC maintains that the true number of annual cases
may be as high as 450,000, since the disease is vastly
underreported. About 85 percent of cases in the
United States are caused by S. sonnei. The Shigella
organisms cause the diarrhea and pain associated
with dysentery by invading the tissues that line the
colon and secreting an enterotoxin, or harmful
protein that attacks the intestinal lining.



Amebic dysentery. Amebic dysentery, which is also
called intestinal amebiasis and amebic colitis, is
caused by a protozoon, Entamoeba histolytica.
E. histolytica, whose scientific name means ‘‘tissuedissolving,’’ is second only to the organism that
causes malaria as a protozoal cause of death.
E. histolytica usually enters the body during the cyst
stage of its life cycle. The cysts may be found in food
or water contaminated by human feces. Once in the
digestive tract, the cysts break down, releasing an
active form of the organism called a trophozoite.
The trophozoites invade the tissues lining the intestine, where they are usually excreted in the patient’s
feces. They sometimes penetrate the lining itself,
however, and enter the bloodstream. If that happens,
the trophozoites may be carried to the liver, lung, or
other organs. Involvement of the liver or other
organs is sometimes called metastatic amebiasis.



Balantidiasis, giardiasis, and cryptosporidiosis.
These three intestinal infections are all caused
by protozoa, Balantidium coli, Giardia lamblia,
and
Cryptosporidium
parvum
respectively.
Although most people infected with these protozoa do not become severely ill, the disease agents
may cause dysentery in children or immunocompromised individuals. There are about 3,500 cases
of cryptosporidiosis reported to the CDC each
year in the United States, and about 22,000
cases of giardiasis.

It should be noted that some doctors use the word
‘‘dysentery’’ to refer only to the first two major types
of dysentery discussed below, while others use the term
in a broader sense. For example, some doctors speak
of schistosomiasis, a disease caused by a parasitic
worm, as bilharzial dysentery, while others refer to
acute diarrhea caused by viruses as viral dysentery.

Description
Dysentery is a common but potentially serious
disorder of the digestive tract that occurs throughout
the world. It can be caused by a number of infectious
agents ranging from viruses and bacteria to protozoa
and parasitic worms; it may also result from chemical
irritation of the intestines. Dysentery is one of the
oldest known gastrointestinal disorders, having been
described as early as the Peloponnesian War in the
fifth century B.C. Epidemics of dysentery were
frequent occurrences aboard sailing vessels as well as
in army camps, walled cities, and other places in the
ancient world where large groups of human beings
lived together in close quarters with poor sanitation.
As late as the eighteenth and nineteenth centuries,
sailors and soldiers were more likely to die from the
‘‘bloody flux’’ than from injuries received in battle. It
was not until 1897 that a bacillus (rod-shaped bacterium) was identified as the cause of one major type of
dysentery.
Dysentery in the modern world is most likely to
affect people in the less developed countries and travelers who visit these areas. According to the Centers
for Disease Control and Prevention (CDC), most
cases of dysentery in the United States occur in immigrants from the developing countries and in persons
who live in inner-city housing with poor sanitation.
Other groups of people at increased risk of dysentery
are military personnel stationed in developing countries, frequent travelers, children in day care centers,
people in nursing homes, and men who have sex with
other men.
GALE ENCYCLOPEDIA OF MEDICINE

1221

Dysentery

Causes & symptoms

Dysentery





Viral dysentery. Viral dysentery, which is sometimes
called traveler’s diarrhea or viral gastroenteritis, is
caused by several families of viruses, including rotaviruses, caliciviruses, astroviruses, noroviruses, and
adenoviruses. There are about 3.5 million cases of
viral dysentery in infants in the United States each
year, and about 23 million cases each year in adults.
The CDC estimates that viruses are responsible for
9.2 million cases of dysentery related to food poisoning in the United States each year. Whereas most
cases of viral dysentery in infants are caused by
rotaviruses, caliciviruses are the most common disease agents in adults. Noroviruses were responsible
for about half of the outbreaks of dysentery on cruise
ships reported to the CDC in 2002.
Dysentery caused by parasitic worms. Both whipworm (trichuriasis) and flatworm or fluke (schistosomiasis) infestations may produce the violent
diarrhea and abdominal cramps associated with
dysentery. Schistosomiasis is the second most widespread tropical disease after malaria. Although the
disease is rare in the United States, travelers to countries where it is endemic may contract it. The World
Health Organization (WHO) estimates that about
200 million people around the world carry the parasite in their bodies, with 20 million having severe
disease.

bloody stools. Fever is unusual with amebiasis unless
the patient has developed a liver abscess as a complication of the infection. The most serious complication of amebic dysentery, however, is fulminant or
necrotizing colitis, which is a severe inflammation of
the colon characterized by dehydration, severe
abdominal pain, and the risk of perforation (rupture)
of the colon.


Dysentery caused by other protozoa. Dysentery
associated with giardiasis begins about 1–3 weeks
after infection with the organism. It is characterized
by bloating and foul-smelling flatus, nausea and
vomiting, headaches, and low-grade fever. These
acute symptoms usually last for three or four days.
The symptoms of cryptosporidiosis are mild in most
patients but are typically severe in patients with
AIDS. Diarrhea usually starts between seven and
10 days after exposure to the organism and may be
copious. The patient may have pain in the upper
right abdomen, nausea, and vomiting, but fever is
unusual.



Viral dysentery. Viral dysentery has a relatively rapid
onset; symptoms may begin within hours of infection. The patient may be severely dehydrated from
the diarrhea but usually has only a low-grade fever.
The diarrhea itself may be preceded by one to three
days of nausea and vomiting. The patient’s abdomen
may be slightly tender but is not usually severely
painful.



Dysentery caused by parasitic worms. Patients with
intestinal schistosomiasis typically have a gradual
onset of symptoms. In addition to bloody diarrhea
and abdominal pain, these patients usually have fatigue. An examination of the patient’s colon will
usually reveal areas of ulcerated tissue, which is the
source of the bloody diarrhea.

Symptoms
In addition to the characteristic bloody and/or
watery diarrhea and abdominal cramps of dysentery,
the various types have somewhat different symptom
profiles:




Bacillary dysentery. The symptoms of shigellosis
may range from the classical bloody diarrhea and
tenesmus characteristic of dysentery to the passage
of nonbloody diarrhea that resembles the loose
stools caused by other intestinal disorders. The high
fever associated with shigellosis begins within one to
three days after exposure to the organism. The
patient may also have pain in the rectum as well as
abdominal cramping. The acute symptoms last for
three to seven days, occasionally for as long as a
month. Bacillary dysentery may lead to two potentially fatal complications outside the digestive tract:
bacteremia (bacteria in the bloodstream), which is
most likely to occur in malnourished children; and
hemolytic uremic syndrome, a type of kidney failure
that has a mortality rate above 50 percent.
Amebic dysentery. Amebic dysentery often has a
slow and gradual onset; most patients with amebiasis
visit the doctor after several weeks of diarrhea and

1222

Diagnosis
Patient history and physical examination
The physical examination in the primary care doctor’s office will not usually allow the doctor to determine the specific parasite or other disease agent that is
causing the bloody diarrhea and other symptoms of
dysentery, although the presence or absence of fever
may help to narrow the diagnostic possibilities. The
patient’s age and history are usually better sources
of information. The doctor may ask about such matters as the household water supply and food preparation habits, recent contact with or employment in a
nursing home or day care center, recent visits to
tropical countries, and similar questions. The doctor
GALE ENCYCLOPEDIA OF MEDICINE

The doctor will also evaluate the patient for signs
of dehydration resulting from the loss of fluid through
the intestines. Fatigue, drowsiness, dryness of the
mucous membranes lining the mouth, low blood pressure, loss of normal skin tone, and rapid heartbeat
(above 100 beats per minute) may indicate that the
patient is dehydrated.

(Imodium), paregoric, and diphenolate (Lomotil),
because they may make the illness worse.


Amebic dysentery. The most common drugs given
for amebiasis are diloxanide furoate (Diloxide),
iodoquinol (Diquinol, Yodoxin), and metronidazole
(Flagyl). Metronidazole should not be given to pregnant women but paromomycin (Humatin) may be
used instead. Patients with very severe symptoms
may be given emetine dihydrochloride or dehydroemetine, but these drugs should be stopped once the
patient’s symptoms are controlled.



Dysentery caused by other protozoa. Balantidiasis,
giardiasis, and cryptosporidiosis are treated with the
same drugs as amebic dysentery; patients with giardiasis resistant to treatment may be given albendazole (Zentel) or furazolidone (Furoxone).



Viral dysentery. The primary concern in treating
viral dysentery, particularly in small children, is to
prevent dehydration. Antinausea and antidiarrhea
medications should not be given to small children.
Probiotics, including Lactobacillus casei and
Saccharomyces boulardii, have been shown to reduce
the duration and severity of viral diarrhea in small
children by 30–70 percent.



Dysentery caused by parasitic worms. Whipworm
infestations are usually treated with anthelminthic medications, most commonly mebendazole
(Vermox). Schistosomiasis may be treated with praziquantel (Biltricide), metrifonate (Trichlorfon), or
oxamniquine, depending on the species causing the
infestation.

Laboratory tests
The most common laboratory test to determine
the cause of dysentery is a stool sample. The patient
should be asked to avoid using over-the-counter antacids or antidiarrheal medications until the sample has
been collected, as these preparations can interfere with
the test results. The organisms that cause cryptosporidiosis, bacillary dysentery, amebic dysentery, and
giardiasis can be seen under the microscope, as can
the eggs produced by parasitic worms. In some cases
repeated stool samples, a sample of mucus from the
intestinal lining obtained through a proctoscope, or a
tissue sample from the patient’s colon may be necessary to confirm the diagnosis. Antigen testing of a
stool sample can be used to diagnose a rotavirus infection as well as parasitic worm infestations.
The doctor will also usually order a blood test to
evaluate the electrolyte levels in the patient’s blood in
order to assess the need for rehydration.
Imaging studies
Imaging studies (usually CT scans, x rays, or
ultrasound) may be performed in patients with amebic
dysentery to determine whether the lungs or liver have
been affected. They may also be used to diagnose
schistosomiasis, as the eggs produced by the worms
will show up on ultrasound or MRI studies of the liver,
intestinal wall, or bladder.

Treatment
Medications are the primary form of treatment
for dysentery:


Bacillary dysentery. Dysentery caused by Shigella is
usually treated with such antibiotics as trimethoprimsulfamethoxazole (Bactrim, Septra), nalidixic acid
(NegGram), or ciprofloxacin (Cipro, Ciloxan).
Because the various species of Shigella are becoming
resistant to these drugs, however, the doctor may
prescribe one of the newer drugs described below.
Patients with bacillary dysentery should not be given
antidiarrheal medications, including loperamide

GALE ENCYCLOPEDIA OF MEDICINE

Newer drugs that have been developed to treat
dysentery include tinidazole (Tindamax, Fasigyn), an
antiprotozoal drug approved by the Food and Drug
Administration (FDA) in 2004 to treat giardiasis and
amebiasis in adults and children over the age of three
years. This drug should not be given to women in the
first three months of pregnancy. In addition, adults
taking tinidazole should not drink alcoholic beverages
while using it, or for three days after the end of treatment. The other new drug is nitazoxanide (Alinia),
another antiprotozoal medication that has the advantage of lacking the bitter taste of metronidazole and
tinidazole.
Fluid replacement is given if the patient has shown
signs of dehydration. The most common treatment is
an oral rehydration fluid containing a precise amount
of salt and a smaller amount of sugar to replace electrolytes as well as water lost through the intestines.
Infalyte and Pedialyte are oral rehydration fluids formulated for the special replacement needs of infants
and young children.
1223

Dysentery

will also need to know when the patient first noticed
the symptoms.

Dysentery

Surgery
Surgery is rarely necessary in treating dysentery,
but may be required in cases of fulminant colitis,
particularly if the patient’s colon has perforated.
Patients with liver abscesses resulting from amebic
dysentery may also require emergency surgery if the
abscess ruptures. In some cases exploratory surgery
may be needed to determine whether severe abdominal
pain is caused by schistosomiasis, amebic dysentery,
or appendicitis.

African mistletoe (Tapinanthus dodoneifolius), a traditional remedy for dysentery among the Hausa and
Fulani tribes of Nigeria.
Dietary supplements
A study published in the American Journal of
Clinical Nutrition in early 2005 reported that supplemental zinc (twice the recommended daily dietary
allowance) boosts the body’s immune response during
acute shigellosis.

Alternative treatments
There are a number of alternative treatments for
dysentery, most of which are derived from plants used
by healers for centuries. Because dysentery was known
to ancient civilizations as well as modern societies,
such alternative systems as traditional Chinese medicine (TCM) and Ayurvedic medicine developed treatments for it.
Ayurvedic medicine
Ayurvedic medicine recommends fruits and herbs,
specifically cumin seed, bael fruit (Aegle marmelos,
also known as Bengal quince), and arjuna
(Terminalia arjuna) bark for the treatment of dysentery. Ayurvedic practitioners may also give the patient
dietary supplements known as Isabbael, Lashunadi
Bati, and Bhuwaneshar Ras. To rehydrate the body,
adult patients may be given a combination of slippery
elm water and barley to drink, at least a pint per day.
Traditional Chinese medicine
To treat dysentery, traditional Chinese doctors
use astringent drugs, which are intended to constrict
or tighten mucous membranes and other body tissues
to slow down fluid loss. Myrobalan fruit (Terminalia
chebula), nut galls (swellings produced on the leaves
and stems of oak trees by the secretions of certain
insects), and opium extracted from the opium poppy
(Papaver somniferum) are the natural materials most
commonly used. Paregoric, a water-based solution of
morphine that is still used in the West to treat diarrhea, is derived from the opium poppy.
Other plant-based remedies
Researchers in Mexico reported in early 2005 that
the roots of Geranium mexicanum, a plant that produces a sap traditionally used to treat coughs or diarrhea, contains compounds that are active against both
Giardia lamblia and Entamoeba histolytica. Plant biologists in Africa are studying the effectiveness of
1224

Homeopathy
There are at least ten different homeopathic remedies used to treat diarrhea. Contemporary homeopaths, however, distinguish between diarrhea that
can be safely treated at home with such homeopathic
remedies as Podophyllum, Veratrum album, Bryonia,
and Arsenicum, and diarrhea that indicates dysentery
and should be referred to a physician. Signs of dehydration (loss of normal skin texture, dry mouth,
sunken eyes), severe abdominal pain, blood in the
stool, and unrelieved vomiting are all indications that
mainstream medical care is required.

Prognosis
Most adults in developed countries recover completely from an episode of dysentery. Children are at
greater risk of becoming dehydrated, however; bacillary dysentery in particular can lead to a child’s death
from dehydration in as little as 12–24 hours.


Bacillary dysentery. Most patients recover completely from shigellosis, although their bowel habits
may not become completely normal for several
months. About 3 percent of people infected by
S. flexneri will develop Reiter’s syndrome, which
may lead to a chronic form of arthritis that is difficult
to treat. Elderly patients or those with weakened
immune systems sometimes develop secondary bacterial infections after an episode of shigellosis.



Amebic dysentery. Most people in North America who
become infected with E. histolytica do not become
severely ill. Patients who develop a severe case of amebic
dysentery, however, are at increased risk for such complications as fulminant colitis or liver abscess. About 0.5
percent of patients with amebic dysentery develop fulminant colitis, but almost half of these patients die.
Between 2 and 7 percent of cases of amebic liver abscess
result in rupture of the abscess with a high mortality rate.
Men are 7–12 times more likely to develop a liver abscess
than women. Any patient diagnosed with amebic dysentery should have stool samples examined for relapse
GALE ENCYCLOPEDIA OF MEDICINE



Dysentery caused by other protozoa. Cryptosporidiosis
may lead to respiratory infections or pancreatitis in
patients with AIDS. The risk of these complications,
however, is reduced in AIDS patients who are receiving
highly active antiretroviral therapy (HAART).



Viral dysentery. Most people in North America
recover completely without complications unless
they become severely dehydrated. Viral dysentery in
children in developing countries, however, is a major
cause of mortality.



KEY TERMS
Anthelminthic (also spelled anthelmintic)—A type
of drug or herbal preparation given to destroy parasitic worms or expel them from the body.
Bacillus—A rod-shaped bacterium. One common
type of dysentery is known as bacillary dysentery
because it is caused by a bacillus.
Enterotoxin—A type of harmful protein released by
bacteria and other disease agents that affects the
tissues lining the intestines.
Fulminant—Occurring or flaring up suddenly and
with great severity. A potentially fatal complication
of amebic dysentery is an inflammation of the
colon known as fulminant colitis.
Probiotics—Food supplements containing live
bacteria or other microbes intended to improve or
restore the normal balance of microorganisms in
the digestive tract.
Proctoscope—An instrument consisting of a thin
tube with a light source, used to examine the inside
of the rectum.

Dysentery caused by parasitic worms. Untreated whipworm infections can lead to loss of appetite, chronic
diarrhea, and retarded growth in children. Untreated
schistosomiasis can develop into a chronic intestinal
disorder in which fibrous tissue, small growths, or
strictures (abnormal narrowing) may form inside the
intestine. Patients treated for schistosomiasis should
have stool samples checked for the presence of worm
eggs 3 and 6 months after the end of treatment.

Prevention

Protozoan (plural, protozoa)—A member of the
simplest form of animal life, a one-celled organism.
Amebic dysentery is caused by a protozoan.

The disease agents that cause dysentery do not
confer immunity against reinfection at a later date.
As of 2005 there are no vaccines for bacillary dysentery or amebic dysentery; however, a vaccine against
schistosomiasis is under investigation. An oral vaccine
against rotavirus infections was developed for small
children but was withdrawn in 2004 because it was
associated with an increased risk of small-bowel disorders. Newer vaccines against rotaviruses and caliciviruses are being developed as of 2005.

Reiter’s syndrome—A group of symptoms that
includes arthritis, inflammation of the urethra, and
conjunctivitis, and develops as a late complication
of infection with Shigella flexneri. The syndrome
was first described by a German doctor named
Hans Reiter in 1918.
Tenesmus—Straining to urinate or defecate without
being able to do so. Tenesmus is a characteristic
feature of bacillary dysentery.
Trophozoite—The active feeding stage of a protozoal parasite, as distinct from its encysted stage.

Public health measures
Public health measures to control the spread of
dysentery include the following:






Requiring doctors to report cases of disease caused
by Shigella, Entamoeba histolytica, and other parasites that cause dysentery. Careful reporting allows
the CDC and state public health agencies to investigate local outbreaks and plan prevention efforts.
Posting advisories for travelers about outbreaks of
dysentery and other health risks in foreign countries.
The Travelers’ Health section of the CDC website
(http://www.cdc.gov/travel/) is a good source of
up-to-date information.
Instructing restaurant workers and other food handlers about proper methods of hand washing, food
storage, and food preparation.

GALE ENCYCLOPEDIA OF MEDICINE



Instructing workers in day care centers and nursing
homes about the proper methods for changing and
cleaning soiled diapers or bedding.



Inspecting wells, other sources of drinking water,
and swimming pools for evidence of fecal
contamination.
Personal precautions

Individuals can lower their risk of contracting
dysentery by the following measures:


Not allowing anyone in the household who has been
diagnosed with amebic or bacillary dysentery to
1225

Dysentery

1, 3, and 6 months after treatment with medications
whether or not they have developed complications.

Dysentery

prepare food or pour water for others until their
doctor confirms that they are no longer carrying the
disease agent.


Avoiding anal sex or oral-genital contacts.



Washing the hands carefully with soap and water
after using the bathroom, and supervising the handwashing of children in day care centers or those at
home who are not completely toilet-trained.



When traveling, drinking only boiled or treated
water, and eating only cooked hot foods or fruits
that can be peeled by the traveler.



Avoiding swimming in fresh water in areas known to
have outbreaks of schistosomiasis.

Resources
BOOKS

Cummings, Stephen, MD, and Dana Ullman, MPH.
Everybody’s Guide to Homeopathic Medicines, revised
and expanded. New York: Jeremy P. Tarcher, 1991.
‘‘Enterobacteriaceae Infections.’’ Section 13, Chapter 161 in
The Merck Manual of Diagnosis and Therapy, edited by
Mark H. Beers, MD, and Robert Berkow, MD.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
‘‘Intestinal Protozoa.’’ Section 13, Chapter 161 in The Merck
Manual of Diagnosis and Therapy, edited by Mark H.
Beers, MD, and Robert Berkow, MD. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine.
New York: Simon & Schuster, 2002.
Reid, Daniel P. Chinese Herbal Medicine. Boston:
Shambhala, 1993.
PERIODICALS

Calzada, F., J. A. Cervantes-Martinez, and L. Yepez-Mulia.
‘‘In vitro Antiprotozoal Activity from the Roots of
Geranium mexicanum and Its Constituents on
Entamoeba histolytica and Giardia lamblia.’’ Journal of
Ethnopharmacology 98 (April 8, 2005): 191–193.
Chijide, Valda M., MD, and Keith F. Woeltje, MD.
‘‘Balantidiasis.’’ eMedicine, 12 March 2002. <http://
www.emedicine.com/med/topic203.htm>.
Deeni, Y. Y., and N. M. Sadiq. ‘‘Antimicrobial Properties
and Phytochemical Constituents of the Leaves of
African Mistletoe (Tapinanthus dodoneifolius (DC)
Danser) (Loranthaceae): An Ethnomedicinal Plant of
Hausalan, Northern Nigeria.’’ Journal of
Ethnopharmacology 83 (December 2002): 235–240.
Eisen, Damon, MD. ‘‘Cryptosporidiosis.’’ eMedicine, 18
November 2004. <http://www.emedicine.com/med/
topic484.htm>.
Goodgame, Richard W., MD. ‘‘Gastroenteritis, Viral.’’
eMedicine, 14 June 2004. <http://www.emedicine.com/
MED/topic856.htm>.
Hlavsa, M. C., J. C. Watson, and M. J. Beach.
‘‘Cryptosporidiosis Surveillance—United States
1226

1999–2002.’’ Morbidity and Mortality Weekly Report,
Surveillance Summaries 54 (January 28, 2005): 1–8.
Hlavsa, M. C., J. C. Watson, and M. J. Beach. ‘‘Giardiasis
Surveillance—United States, 1998–2002.’’ Morbidity
and Mortality Weekly Report, Surveillance Summaries
54 (January 28, 2005): 9–16.
Hu, F., R. Lu, B. Huang, and M. Liang. ‘‘Free Radical
Scavenging Activity of Extracts Prepared from Fresh
Leaves of Selected Chinese Medicinal Plants.’’
Fitoterapia 75 (January 2004): 14–23.
Kroser, Joyann A., MD. ‘‘Shigellosis.’’ eMedicine, 17 May
2002. <http://www.emedicine.com/med/
topic2112.htm>.
Nachimuthu, Senthil, MD, and Paul Piccione, MD. ‘‘Food
Poisoning.’’ eMedicine, 10 January 2005. <http://
www.emedicine.com/med/topic807.htm>.
Pennardt, Andre, MD. ‘‘Giardiasis.’’ eMedicine, 25 June
2004. <http://www.emedicine.com/emerg/
topic215.htm>.
Rahman, M. J., P. Sarker, S. K. Roy, et al. ‘‘Effects of Zinc
Supplementation as Adjunct Therapy on the Systemic
Immune Responses in Shigellosis.’’ American Journal of
Clinical Nutrition 81 (February 2005): 495–502.
Scoggins, Thomas, MD, and Igor Boyarsky, DO. ‘‘Reiter
Syndrome.’’ eMedicine, 7 December 2004. <http://
www.emedicine.com/EMERG/topic498.htm>.
Swords, Robert, MD, and J. Robert Cantey, MD.
‘‘Amebiasis.’’ eMedicine, 22 February 2002. <http://
www.emedicine.com/med/topic116.htm>.
White, C. A. Jr. ‘‘Nitazoxanide: A New Broad-Spectrum
Antiparasitic Agent.’’ Expert Review of Anti-Infective
Therapy 2 (February 2004): 43–49.
Wingate, D., S. F. Phillips, S. J. Lewis, et al. ‘‘Guidelines for
Adults on Self-Medication for the Treatment of Acute
Diarrhea.’’ Alimentary Pharmacology and Therapeutics
15 (June 2001): 773–782.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>
Infectious Diseases Society of America (IDSA). 66 Canal
Center Plaza, Suite 600, Alexandria, VA 22314. (703)
299-0200. Fax: (703) 299-0204. <http://
www.idsociety.org>.
World Health Organization (WHO). <http://www.who.int/
en/>.
OTHER

Centers for Disease Control and Prevention. Disease
Information. ‘‘Shigellosis.’’ <http://www.cdc.gov/
ncidod/dbmd/diseaseinfo/shigellosis_t.htm>
Centers for Disease Control and Prevention, Division of
Parasitic Diseases. Fact Sheet. ‘‘Amebiasis.’’ <http://
www.cdc.gov/ncidod/dpd/parasites/amebiasis/
factsht_amebiasis.htm>
Centers for Disease Control and Prevention, National
Center for Infectious Diseases, Travelers’ Health. ‘‘New
Medication Approved for Treatment of Giardiasis and
GALE ENCYCLOPEDIA OF MEDICINE

Rebecca Frey, PhD

Metrorrhagia
Metrorrhagia is bleeding between menstrual periods. Bleeding is heavy and irregular as opposed to
ovulatory spotting which is light bleeding, in midcycle, at the time of ovulation.
Polymenorrhea

I Dysfunctional
uterine
bleeding
Definition
Dysfunctional uterine bleeding is irregular,
abnormal uterine bleeding that is not caused by a
tumor, infection, or pregnancy.

Description
Dysfunctional uterine bleeding (DUB) is a disorder that occurs most frequently in women at the beginning and end of their reproductive lives. About half
the cases occur in women over 45 years of age, and
about one fifth occur in women under age 20.
Dysfunctional uterine bleeding is diagnosed when
other causes of uterine bleeding have been eliminated.
Failure of the ovary to release an egg during the menstrual cycle occurs in about 70% of women with DUB.
This is probably related to a hormonal imbalance.
DUB is common in women who have polycystic
ovary syndrome (cysts on the ovaries). Women who
are on dialysis may also have heavy or prolonged
periods. So do some women who use an intrauterine
device (IUD) for birth control.
DUB is similar to several other types of uterine
bleeding disorders and sometimes overlaps these
conditions.
Menorrhagia
Menorrhagia, sometimes called hypermenorrhea,
is another term for abnormally long, heavy periods.
This type of period can be a symptom of DUB, or
many other diseases or disorders. In menorrhagia, menstrual periods occur regularly, but last more than seven
days, and blood loss exceeds 3 oz (88.7 ml). Passing
blood clots is common. Between 15–20% of healthy
women experience debilitating menorrhagia that interferes with their normal activities. Menorrhagia may or
may not signify a serious underlying problem.
GALE ENCYCLOPEDIA OF MEDICINE

Polymenorrhea describes the condition of having
too frequent periods. Periods occur more often than
every 21 days, and ovulation usually does not occur
during the cycle.

Causes and symptoms
Dysfunctional uterine bleeding often occurs when
the endometrium, or lining of the uterus, is stimulated
to grow by the hormone estrogen. When exposure to
estrogen is extended, or not balanced by the presence
of progesterone, the endometrium continues to grow
until it outgrows its blood supply. Then it sloughs off,
causing irregular bleeding. If the bleeding is heavy
enough and frequent enough, anemia can result.
Menorrhagia is representative of DUB. It is
caused by many conditions including some outside
the reproductive system. Causes of menorrhagia
include:


adenomyosis (a benign condition characterized by
growths in the area of the uterus)



imbalance between the hormones estrogen and
progesterone



fibroid tumors



pelvic infection



endometrial cancer (cancer of the inner mucous
membrane of the uterus)



endometrial polyps



endometriosis (a condition in which endometrial
or endrometrial-like tissue appears outside of its
normal place in the uterus)



use of an intrauterine device (IUD) for contraception



hypothyroidism



blood clotting problems (rare)



lupus erythematosus



pelvic inflammatory disease



steroid therapy



advanced liver disease



renal (kidney) disease



chemotherapy (cancer treatment with chemicals)
1227

Dysfunctional uterine bleeding

Amebiasis.’’ <http://www.cdc.gov/travel/other/
tinidazole_approval_2004.htm>
World Health Organization. ‘‘Shigella.’’ <http://
www.who.int/topics/shigella/en/>.

Dysfunctional uterine bleeding

To diagnose dysfunctional uterine bleeding,
many of the potential causes mentioned above must
be eliminated. When all potential causes connected
with pregnancy, infection, and tumors (benign or
malignant) are eliminated, then menorrhagia is presumed to be caused by dysfunctional uterine
bleeding.

Diagnosis
Diagnosis of any menstrual irregularity begins
with the patient herself. The doctor will ask for a
detailed description of the problem, and take a
history of how long it has existed, and any patterns
the patient has observed. A woman can assist the
doctor in diagnosing the cause of abnormal uterine
bleeding by keeping a record of the time, frequency, length, and quantity of bleeding. She
should also tell the doctor about any illnesses,
including long-standing conditions, like diabetes
mellitus. The doctor will also inquire about sexual
activity, use of contraceptives, current medications,
and past surgical procedures.
Laboratory tests
After taking the woman’s history, the gynecologist or family practitioner does a pelvic examination
and Pap smear. To rule out specific causes of abnormal bleeding, the doctor may also do a pregnancy test
and blood tests to check the level of thyroid hormone.
Based on the initial test results, the doctor may want to
do tests to determine the level of other hormones that
play a role in reproduction. A test of blood clotting
time and an adrenal function test are also commonly
done.
Imaging
Imaging tests are important diagnostic tools for
evaluating abnormal uterine bleeding. Ultrasound
examination of the pelvic and abdominal area is used
to help locate uterine fibroids, also called uterine leiomyoma, a type of tumor. Visual examination through
hysterscopy–where a camera inside a thin tube is
inserted directly into the uterus so that the doctor
can see the uterine lining–is also used to assess the
condition of the uterus.
Hystersalpingography can help outline endometrial polyps and fibroids and help detect endometrial
cancer. In this procedure an x ray is taken after contrast media has been injected into the cervix. Magnetic
resonance imaging (MRI) of the pelvic region can also
be used to locate fibroids and tumors.
1228

Invasive procedures
Endometrial biopsy (the removal and examination
of endometrial tissue) is the most important testing
procedure. It allows the doctor to sample small areas
of the uterine lining, while cervical biopsy allows the
cervix to be sampled. Tissues are then examined for
any abnormalities.
Dilation and curettage (D & C), once common is
rarely done today for diagnosis of DUB. It is done
while the patient is under either general or regional
anesthesia. Women over 30 are more likely to need a
D & C, as part of the diagnostic procedure, than
younger women.
Because DUB is diagnosed by eliminating other
possible disorders, diagnosis can take a long time and
involve many tests and procedures. Older women are
likely to need more extensive tests than adolescents
because the likelihood of reproductive cancers is
greater in this age group, and therefore must be definitively eliminated before treating bleeding symptoms.

Treatment
Treatment of DUB depends on the cause of the
bleeding and the age of the patient. When the underlying cause of the disorder is known, that disorder is
treated. Otherwise the goal of treatment is to relieve
the symptoms to a degree that uterine bleeding does
not interfere with a woman’s normal activities or cause
anemia.
Generally the first approach to controlling DUB
is to use oral contraceptives that provide a balance
between the hormones estrogen and progesterone.
Oral contraceptives are often very effective in adolescents and young women in their twenties. NSAIDs
(nonsteroidal anti-inflammatory drugs), like Naprosyn
and Motrin, are also used to treat DUB.
When bleeding cannot be controlled by hormone
treatment, surgery may be necessary. Dilation and
curettage sometimes relieves the symptoms of DUB.
If that fails, endometrial ablation removes the uterine
lining, but preserves a woman’s uterus. This procedure
is sometimes be used instead of hysterectomy.
However, as it affects the uterus, it can only be used
when a woman has completed her childbearing years.
The prescription of iron is also important to decrease
the risk of enemia.
Until the 1980s, hysterectomy often was used to
treat heavy uterine bleeding. Today hysterectomy is
used less frequently to treat DUB, and then only after
other methods of controlling the symptoms have failed.
A hysterectomy leaves a woman unable to bear children,
GALE ENCYCLOPEDIA OF MEDICINE

Dilation and curettage (D & C)—A procedure performed under anesthesia during which the cervix is
dilated, and tissue lining the uterus is scraped out
with a metal spoon-shaped instrument or a suction
tube. The procedure can be either diagnostic, or to
remove polyps.
Endometrial biopsy—The removal of tissue either
by suction or scraping of samples of tissue from the
uterus. The cervix is not dilated. The procedure has
a lower rate of diagnostic accuracy than a D & C,
but can be done as an office procedure under local
anesthesia.
Endometrial cancer—Cancer of the inner mucous
membrane of the uterus.
Fibroids, or fibroid tumors—Fibroid tumors are
non-cancerous (benign) growths in the uterus.
They occur in 30–40% of women over age 40,
and do not need to be removed unless they are
causing symptoms that interfere with a woman’s
normal activities.
Hypothyroidism—A disorder in which the thyroid
gland produces too little thyroid hormone causing
a decrease in the rate of metabolism with associated effects on the reproductive system.
Lupus erythematosus—A chronic inflammatory
disease in which inappropriate immune system
reactions cause abnormalities in the blood vessels
and connective tissue.
Progesterone—A hormone naturally secreted by
the ovary, or manufactured synthetically, that prepares the uterus for implantation of a fertilized egg.
Prostaglandins—A group of chemicals that
mediate, or determine the actions of other chemicals in the cell or body.

also appears to reduce menorrhagia in many women.
Other recommended dietary supplements include vitamins A and C. Vitamin C improves capillary fragility
and enhances iron uptake.
Vitamin E and bioflavonoid supplements are also
recommended. Vitamin E can help reduce blood flow,
and bioflavonoids help strengthen the capillaries.
Vitamin K is known to play a role in clotting and is
helpful in situations where heavy bleeding may be due
to clotting abnormalities
Botanical medicines used to assist in treating
abnormal bleeding include spotted cranesbill
(Geranium maculatum), birthroot (Trillium pendulum),
blue cohosh (Caulophyllum thalictroides), witch hazel
(Hamamelis virginiana), shepherd’s purse (Capsella
bursa-pastoris), and yarrow (Achillea millifolia).
These are all stiptic herbs that act to tighten blood
vessels and tissue. Hormonal balance can also be
addressed with herbal formulations containing
phytoestrogens and phytoprogesterone.

Prognosis
Response to treatment for DUB is highly individual
and is not easy to predict. The outcome depends largely
on the woman’s medical condition and her age. Many
women, especially adolescents, are successfully treated
with hormones (usually oral contraceptives). As a last
resort, hysterectomy removes the source of the problem
by removing the uterus, but this operation is not without
risk, or the possibility of complications.

Prevention
Dysfunctional uterine bleeding is not a preventable disorder.
Resources
OTHER

‘‘Menorrhagia.’’ The Wellness Web. <http://wellweb.com/
INDEX/MENORRHAGIA.htm>.

and, therefore, is limited largely to women who are
unable to, or uninterested in, bearing children. Still,
hysterectomy is a common treatment for long-standing
DUB in women done with childbearing.

Alternative treatment
Alternative practitioners concentrate on good
nutrition as a way to prevent heavy periods that are
not caused by uterine fibroids, endometrial polyps,
endometriosis, or cancer. Iron supplementation
(100 mg per day) not only helps prevent anemia, but
GALE ENCYCLOPEDIA OF MEDICINE

Tish Davidson, A.M.

I Dyslexia
Definition
Dyslexia is a learning disability characterized by
problems in reading, spelling, writing, speaking, or
1229

Dyslexia

KEY TERMS

Dyslexia

listening. In many cases, dyslexia appears to be
inherited.

Description
The word dyslexia is derived from the Greek
word, dys (meaning poor or inadequate) and the
word lexis (meaning words or language).
The National Institutes of Health estimates that
about 15% of the United States population is affected
by learning disabilities, mostly with problems in language and reading. The condition appears in all ages,
races, and income levels. Dyslexia is not a disease, but
describes rather a different kind of mind that learns in
a different way from other people. Many people with
the condition are gifted and very productive; dyslexia
is not at all linked to low intelligence. In fact, intelligence has nothing to do with dyslexia.
Dyslexic children seem to have trouble learning
early reading skills, problems hearing individual
sounds in words, analyzing whole words in parts,
and blending sounds into words. Letters such as ‘‘d’’
and ‘‘b’’ may be confused.
When a person is dyslexic, there is often an unexpected difference between achievement and aptitude.
However, each person with dyslexia has different
strengths and weaknesses, although many have unusual talents in art, athletics, architecture, graphics,
drama, music, or engineering. These special talents
are often in areas that require the ability to integrate
sight, spatial skills, and coordination.
Often, a person with dyslexia has a problem translating language into thought (such as in listening or
reading), or translating thought into language (such as
in writing or speaking).
Common characteristics include problems with:


identifying single words



understanding sounds in words, sound order, or
rhymes



spelling



transposing letters in words



handwriting



reading comprehension



delayed spoken language



confusion with directions, or right/left handedness



confusion with opposites (up/down, early/late, and
so on)



mathematics

1230

Causes and symptoms
The underlying cause of dyslexia is not known,
although research suggests the condition is often
inherited. In 1999, The Centre for Reading Research
in Norway presented the first research to study the
largest family with reading problems ever known. By
studying the reading and writing abilities of close to 80
family members across four generations the researchers reported, for the first time, that chromosome 2 can
be involved in the inheritability of dyslexia. When a
fault occurs on this gene it leads to difficulties in
processing written language. Previous studies have
pointed out linkages of other potential dyslexia genes
to chromosome 1, chromosome 15 (DYX1 gene), and
to chromosome 6 (DYX2 gene). The researchers who
pinpointed the newly localized gene on chromosome 2
(DYX3) hope that this finding will lead to earlier and
more precise diagnoses of dyslexia.
New research suggests a possible link with a subtle
visual problem that affects the speed with which
affected people can read. Other experts believe that
dyslexia is related to differences in the structure and
function of the brain that manifests differently in different people.

Diagnosis
Anyone who is suspected to have dyslexia should
have a comprehensive evaluation, including hearing,
vision, and intelligence testing. The test should include
all areas of learning and learning processes, not just
reading.
As further research pinpoints the genes responsible for some cases of dyslexia, there is a possibility that
earlier testing will be established to allow for timely
interventions to prevent the onset of the condition and
to treat it when it does occur. Unfortunately, in many
schools, a child is not identified as having dyslexia
until after repeated failures.

Treatment
If a child is diagnosed with dyslexia, the parents
should find out from the school or the diagnostician
exactly what the problem is, and what method of
teaching is recommended and why. No single method
will work with every child, and experts often disagree
as to the best method to use.
The primary focus of treatment is aimed at helping the specific learning problem of each affected person. Most often, this may include modifying teaching
methods and the educational environment, since
GALE ENCYCLOPEDIA OF MEDICINE

Dyslexia

•

(_

A student with dyslexia has difficulty copying words. (Photograph by Will & Deni McIntyre, Photo Researchers, Inc. Reproduced by
permission.)

Prognosis

KEY TERMS
Spatial skills—The ability to locate objects in three
dimensional world using sight or touch.

traditional educational methods will not always work
with a dyslexic child.
People with dyslexia need a structured language
program, with direct instruction in the letter-sound
system. Teachers must give the rules governing written language. Most experts agree that the teacher
should emphasize the association between simple
phonetic units with letters or letter groups, rather
than an approach that stresses memorizing whole
words.
It is important to teach these students using all
the senses: hearing, touching, writing, and speaking, provided by an instructor who is specifically
trained in a program that is effective for dyslexic
students.
GALE ENCYCLOPEDIA OF MEDICINE

Many successful and even famous people have
dyslexia. How well a person with dyslexia functions
in life depends on the way the disability affects that
person. There is a great deal of variation among different people with dyslexia, producing different symptoms and different degrees of severity.
Prognosis is usually good if the condition is diagnosed early, and if the person has a strong self image
with supportive family, friends, and teachers. It is
imperative for a good outcome that the person be
involved in a good remedial program.
Resources
PERIODICALS

Fagerheim, Toril, et al. ‘‘A New Gene (DYX3) for Dyslexia
is Located on Chromosome 2.’’ Journal of Medical
Genetics 36 (September 1999): 664-669.

Beth A. Kapes

Dyslipidemia see Hyperlipoproteinemia
1231

Dysmenorrhea

I Dysmenorrhea
Definition
Dysmenorrhea is the occurrance of painful
cramps during menstruation.

Description
More than half of all girls and women suffer from
dysmenorrhea (cramps), a dull or throbbing pain that
usually centers in the lower mid-abdomen, radiating
toward the lower back or thighs. Menstruating women
of any age can experience cramps.
While the pain may be only mild for some women,
others experience severe discomfort that can significantly interfere with everyday activities for several
days each month.

Causes and symptoms
Dysmenorrhea is called ‘‘primary’’ when there is no
specific abnormality, and ‘‘secondary’’ when the pain is
caused by an underlying gynecological problem. It
is believed that primary dysmenorrhea occurs when
hormone-like substances called ‘‘prostaglandins’’
produced by uterine tissue trigger strong muscle contractions in the uterus during menstruation. However,
the level of prostaglandins does not seem to have
anything to do with how strong a woman’s cramps
are. Some women have high levels of prostaglandins
and no cramps, whereas other women with low levels
have severe cramps. This is why experts assume that
cramps must also be related to other things (such as
genetics, stress, and different body types) in addition to
prostaglandins. The first year or two of a girl’s periods
are not usually very painful. However, once ovulation
begins, the blood levels of the prostaglandins rise, leading to stronger contractions.
Secondary dysmenorrhea may be caused by endometriosis, fibroid tumors, or an infection in the pelvis.
The likelihood that a woman will have cramps
increases if she:


has a family history of painful periods



leads a stressful life



does not get enough exercise



uses caffeine



has pelvic inflammatory disease

Symptoms include a dull, throbbing cramping in
the lower abdomen that may radiate to the lower back
and thighs. In addition, some women may experience
1232

nausea and vomiting, diarrhea, irritability, sweating, or
dizziness. Cramps usually last for two or three days at
the beginning of each menstrual period. Many women
often notice their painful periods disappear after they
have their first child, probably due to the stretching of
the opening of the uterus or because the birth improves
the uterine blood supply and muscle activity.

Diagnosis
A doctor should perform a thorough pelvic exam
and take a patient history to rule out an underlying
condition that could cause cramps.

Treatment
Secondary dysmenorrhea is controlled by treating
the underlying disorder.
Several drugs can lessen or completely eliminate
the pain of primary dysmenorrhea. The most popular
choice are the nonsteroidal anti-inflammatory drugs
(NSAIDs), which prevent or decrease the formation of
prostaglandins. These include aspirin, ibuprofen
(Advil), and naproxen (Aleve). For more severe pain,
prescription strength ibuprofen (Motrin) is available.
These drugs are usually begun at the first sign of the
period and taken for a day or two. There are many
different types of NSAIDs, and women may find that
one works better for them than the others.
If an NSAID is not available, acetaminophen
(Tylenol) may also help ease the pain. Heat applied to
the painful area may bring relief, and a warm bath twice a
day also may help. While birth control pills will ease the
pain of dysmenorrhea because they lead to lower hormone levels, they are not usually prescribed just for pain
management unless the woman also wants to use them as
a birth control method. This is because these pills may
carry other more significant side effects and risks.
New studies of a drug patch containing glyceryl
trinitrate to treat dysmenorrhea suggest that it also
may help ease pain. This drug has been used in the
past to ease preterm contractions in pregnant women.

Alternative treatment
Simply changing the position of the body can help
ease cramps. The simplest technique is assuming the
fetal position, with knees pulled up to the chest while
hugging a heating pad or pillow to the abdomen.
Likewise, several yoga positions are popular ways to
ease menstrual pain. In the ‘‘cat stretch,’’ position, the
woman rests on her hands and knees, slowly arching
the back. The pelvic tilt is another popular yoga
GALE ENCYCLOPEDIA OF MEDICINE

Endometriosis—The growth of uterine tissue outside the uterus.
Hormone—A chemical messenger secreted by a
gland and released into the blood, which allows it
to travel to distant cells where it exerts an effect.
Ovary—One of the two almond-shaped glands in
the female body that produces the hormones estrogen and progesterone.
Ovulation—The monthly release of an egg from an
ovary.

PERIODICALS

McDonald, Claire, and Susan McDonald. ‘‘A Woman’s
Guide to Self-care.’’ Natural Health January-February
1998:121-142.
ORGANIZATIONS

National Women’s Health Network. 514 10th St. NW, Suite
400, Washington, DC 20004. (202) 628-7814. <http://
www.womenshealthnetwork.org>.

Carol A. Turkington

Dysmetria see Movement disorders

Progesterone—The hormone produced by the
ovary after ovulation that prepares the uterine lining for a fertilized egg.
Uterus—The female reproductive organ that contains
and nourishes a fetus from implantation until birth.

I Dyspepsia
Definition

position, in which the woman lies with knees bent, and
then lifts the pelvis and buttocks.
Dietary recommendations to ease cramps include
increasing fiber, calcium, and complex carbohydrates,
cutting fat, red meat, dairy products, caffeine, salt,
and sugar. Smoking also has been found to worsen
cramps. Recent research suggests that vitamin B supplements, primarily vitamin B6 in a complex, magnesium, and fish oil supplements (omega-3 fatty acids)
also may help relieve cramps.
Other women find relief through visualization,
concentrating on the pain as a particular color and
gaining control of the sensations. Aromatherapy and
massage may ease pain for some women. Others find
that imagining a white light hovering over the painful
area can actually lessen the pain for brief periods.
Exercise may be a way to reduce the pain of menstrual cramps through the brain’s production of
endorphins, the body’s own painkillers. And orgasm
can make a woman feel more comfortable by releasing
tension in the pelvic muscles.
Acupuncture and Chinese herbs are another
popular alternative treatments for cramps.

Prognosis
Medication should lessen or eliminate pain.

Prevention
NSAIDs taken a day before the period begins
should eliminate cramps for some women.
GALE ENCYCLOPEDIA OF MEDICINE

Dyspepsia can be defined as painful, difficult, or
disturbed digestion, which may be accompanied by
symptoms such as nausea and vomiting, heartburn,
bloating, and stomach discomfort.

Causes and symptoms
The digestive problems may have an identifiable
cause, such as bacterial or viral infection, peptic ulcer,
gallbladder, or liver disease. The bacteria Helicobacter
pylori is often found in those individuals suffering
from duodenal or gastric ulcers. Investigation of
recurrent indigestion should rule out these possible
causes.
Often, there is no organic cause for the problem,
in which case dyspepsia is classified as functional or
nonulcer dyspepsia. There is evidence that functional
dyspepsia may be related to abnormal motility of the
upper gastrointestinal tract (a state known as dysmotility in which the esophagus, stomach, and upper
intestine behave abnormally). These patients may
respond to a group of drugs called prokinate agents.
A review of eating habits (e.g., chewing with the
mouth open, gulping food, or talking while chewing)
may reveal a tendency to swallow air. This may contribute to feeling bloated, or to excessive belching.
Smoking, caffeine, alcohol, or carbonated beverages
may contribute to the discomfort. When there is sensitivity or allergy to certain food substances, eating
those foods may cause gastrointestinal distress. Some
medications are associated with indigestion. Stomach
problems may also be a response to stress or emotional
unrest.
1233

Dyspepsia

Resources

KEY TERMS

Dysphasia

KEY TERMS
Anemia—Diagnosed through laboratory study of
the blood, a deficiency in hemoglobin or red
blood cells, often associated with paleness or loss
of energy.
Endoscopy—A diagnostic procedure using a
lighted instrument to examine a body cavity or
internal organ. Endoscopy permits collection of
tissue and culture specimens.

palpable mass, or anemia. Additional work-up is also
indicated if a patient does not respond to prescribed
medications.

Prognosis
A false-color gamma scan of a human stomach with dyspepsia, or indigestion, during tests to study its rate of emptying.
(Photograph by Jean-Perrin, Custom Medical Stock Photo.
Reproduced by permission.)

Diagnosis
A physical examination by a health care professional may reveal mid-abdominal pain. A rectal examination may be done to rule out bleeding. If blood is
found on rectal exam, laboratory studies, including a
blood count may be ordered. Endoscopy and barium
studies may be used to rule out underlying gastrointestinal disease. Upper gastrointestinal x-ray studies
using barium may allow for visualization of abnormalities. Endoscopy permits collection of tissue and
culture specimens which may be used to further confirm a diagnosis.

Treatment
The treatment of dyspepsia is based on assessment
of symptoms and suspected causative factors. Clinical
evaluation is aimed at distinguishing those patients
who require immediate diagnostic work-ups from
those who can safely benefit from more conservative
initial treatment. Some of the latter may require only
reassurance, dietary modifications, or antacid use.
Medications to block production of stomach acids,
prokinate agents, or antibiotic treatment may be considered. Further diagnostic investigation is indicated if
there is severe abdominal pain, pain radiating to the
back, unexplained weight loss, difficulty swallowing, a
1234

Statistics show an average of 20% of patients with
dyspepsia have duodenalor gastric ulcer disease, 20%
have irritable bowel syndrome, fewer than 1% of
patients had cancer, and the range for functional, or
non-ulcer dyspepsia (gastritis or superficial erosions),
was from 5–40%.
Resources
PERIODICALS

Talley, N. J. ‘‘Non-ulcer Dyspepsia: Current Approaches to
Diagnosis and Management.’’ American Family
Physician May 1993: 1407-1416.
OTHER

‘‘Clinical Economics: Gastrointestinal Disease in Primary
Care.’’ April 23, 1998. <http://www.avicenna.com>.

Kathleen D. Wright, RN

I Dysphasia
Definition
Dysphasia is a partial or complete impairment of
the ability to communicate resulting from brain injury.

Description
Approximately one million Americans currently
suffer from one of the various forms of dysphasia, and
an additional 80,000 new cases occur annually. The
term ‘‘dysphasia’’ is more frequently used by
GALE ENCYCLOPEDIA OF MEDICINE

Verbal communication is derived from several
regions located in the language-dominant hemisphere
of the brain. These include the adjacent inferior parietal lobe, the inferolateral lobe, and the posterosuperior temporal lobe, as well as the subcortical connection
between these areas. Disease, direct trauma, lesion,
or infarction involving one or more of these regions
can disrupt or prevent proper language function.
Dysphasia does not necessarily prevent proper cognitive function, so the patient can think and feel with
perfect clarity. This can be extremely frustrating for
the patient, as they cannot express these thoughts and
feelings to others.
Dysphasia can occur in a variety of forms,
depending on how the communicative disruption
manifests. Classically, dysphasia can affect one or
more of the basic language functions: comprehension
(understanding spoken language), naming (identifying
items with words), repetition (repeating words or
phrases), and speech. Although there are several subtypes of dysphasias, they most commonly manifest in
one of three syndromes: expressive dysphasia, receptive dysphasia, or global dysphasia.
Expressive Dysphasia
Expressive dysphasia, also known as motor dysphasia, produces a conscious and recognizable disruption of a patient’s speech production and language
output. This includes the impairment of speech initiation, proper grammatical sequencing, and proper
word forming and articulation. Although patients
can perfectly understand what is said to them, they
have great difficulty communicating their thoughts.
BROCA’S DYSPHASIA. Broca’s dysphasia is the
most common type of expressive dysphasia. It is
caused by damage to the lower area of the premotor
cortex, located just in front of the primary motor
cortex. This region is most commonly referred to as
the Broca’s area. Speech for patients suffering from
Broca’s dysphasia may be completely impossible.
Others may be able to form single words or full sentences, but only through great effort. ‘‘Telegraphing,’’
the omission of articles and conjunctions, may also be
exhibited.

GALE ENCYCLOPEDIA OF MEDICINE

TRANSCORTICAL DYSPHASIA. Also known as isolation syndrome, transcortical dysphasia is caused by
damage to the language-dominant brain that separates all or parts of the central region from the rest of
the brain. There are three sub-classes of transcortical
dysphasia, which define the impairments to a patient’s
ability to repeat words, sentences, and phrases:
transcortical motor dysphasia, transcortical sensory
dysphasia, and mixed transcortical dysphasia.
Additional impairments may occur depending on the
extent and location of the damage.

Receptive Dysphasia
Receptive dysphasia, also known as sensory dysphasia, impairs the patient’s comprehension and
meaning of language. Unlike expressive dysphasia,
the patient can speak fluently and articulately, but
will utilize meaningless words, nonsensical grammar,
and unnecessary phrases to the point of becoming
incomprehensible. However, they will be completely
unaware of their mistakes. Additionally, the patient
will find it difficult to comprehend spoken language
and/or word-object relation.
WERNICKE’S DYSPHASIA. Also known as semantic
dysphasia, Wernicke’s dysphasia is the most common
of the receptive dysphasia. It is caused by damage to
the Wernicke’s area, located in the posterior superior
temporal lobe of the language-dominant hemisphere.
Although the patient can speak clearly and at length,
many of their words, phases, and sentences will be
nonsensical in nature. Additionally, they will experience difficulty in understanding spoken language, if
not suffer a complete lack of comprehension.
Semantic distinctions between words may become
mixed up and jumbled, furthering confusion.
ANOMIC DYSPHASIA. Anomic dysphasia, also
referred to as amnesic dysphasia, is caused by damage
to the temporal parietal area and/or the angular gyrus
region. Although very similar to Wernicke’s dysphasia, anomic dysphasia is distinguished by its disruption
of a patient’s word-retrieval skills. They will be unable
to correctly name people or objects, causing them to
pause or substitute generalized words (like ‘‘thing’’).
Otherwise, the patient will exhibit few, if any, language
impairments.
CONDUCTION DYSPHASIA. Also known as associative dysphasia, conduction dysphasia is a relatively
uncommon disease (representing only 10% of the
cases). Damage to the upper temporal lobe, lower
parietal, or connection between the Wernicke’s and
Broca’s areas can result in the inability to repeat
words, phrases, or sentences. The patient may also

1235

Dysphasia

European health professionals, whereas in North
American the term, aphasia is more commonly preferred. These two terms, however, can be and are used
interchangeably. They both refer to the full or partial
loss of verbal communication skills due to damage
or degeneration of the brain’s language centers.
Developmental Dysphasia is considered to be a learning disability, but will not be the focus of this article.

Dysphasia

suffer the inability to describe people or objects in the
proper terms.
Global Dysphasia
Global dysphasia, the third most common form of
dysphasia, results from damage to both the anterior
and posterior regions of the language-dominant hemisphere. In global dysphasia, all of the patient’s language skills are disrupted; however, some may be
disrupted more severely than others.

Causes & symptoms
Currently, over one million people in the United
States suffer a permanent type of dysphasia. Although
dysphasia may manifest in several ways, the common
cause for its onset is damage or trauma to the brain.
Stroke, in particular, is the most common cause for
dysphasia. Of the half million stroke victims reported
annually in the United States, approximately 100,000
will suffer some form of dysphasia. Infection, direct
trauma, transient ischemic attack (TIA), brain tumors,
and degeneration can also instigate the onset of
dysphasia.
Symptoms of dysphasia will quickly manifest
after damage to the brain has occurred, and will present in accordance to the particular type of dysphasia
suffered. Due to the proximity to areas of the brain
that control motor function, expressive dysphasias can
be accompanied by noticeable motor impairment. The
majority of symptoms will be language related,
including:


Difficulty remembering words



Difficulty naming objects and/or people



Difficulty speaking in complete and/or meaningful
sentences



Difficulty speaking in any fashion



Difficulty reading or writing



Difficulty expressing thoughts and feelings



Difficulty understanding spoken language



Using incorrect or jumbled words



Using words in the wrong order

Diagnosis
Dysphasia is frequently diagnosed while the
patient is being treated for injury to the brain, be it
from trauma or disease. The health professional, typically a neurologist, will conduct standard cognitive
tests, including tests to determine whether the
1236

patient’s language centers have been affected. If the
patient exhibits signs of difficulty communicating,
they will often be referred to a speech-language pathologist. In turn, the pathologist will conduct a comprehensive examination of the patient’s ability language
and comprehension skills. This examination may begin
with evaluating the patient’s ability to repeat words and
phrases, recognize and describe objects, and comprehend what is said to them. More extensive and standardized language-based tests may be required, including
the Porch Index of Speech Ability and the Boston
Diagnostic Aphasia Examination. Based on the result
of the examinations, the health professional will be able
to determine the type of dysphasia inflicting the patient.
More extensive damage may require the use of computed tomography or magnetic resonance imaging for
an effective diagnosis.

Treatment
Initially it is necessary to treat and stabilize the
injury underlying the development of the patient’s
dysphasia. In some cases, such as with damage caused
by TIA, a full recovery can be expedient and take only
a few days. Unfortunately, most dysphasias can take
months, if not years, to recover from. Even after prolonged therapy, many patients never achieve a full
recovery. Efficacy of treatment greatly depends on
the promptness with which it begins. For this reason,
many medical facilities have speech-language pathologists on staff to begin the initial treatment process as
quickly as possible.
There is no medical or surgical cure for dysphasia.
Treatment, instead, relies strongly upon the use of
various speech therapies. Much like physical therapy
strengthens muscles and bones back to normalcy,
speech therapy allow the patient to regain language
function, as well as rebuild their communications
skills. Treatment is typically conducted with a trained
speech therapist. However, group sessions are common and allow the patient to practice their language
skills in a non-threatening environment with others
sharing their disability. Although much of therapeutic
work is conducted by a speech therapist, friends and
family also play a vital role in the patient’s recovery.
They can help the patient continually practice and
exercise language skills while outside the therapeutic
setting. Many times, family members are included on
therapy sessions to teach them how to communicate
with and understand the patient.
There are several treatments available, which utilize the patient’s remaining language abilities to
rebuild and compensate for those that were lost.
GALE ENCYCLOPEDIA OF MEDICINE

Transient ischemic attack—Also known as a ministroke, a transient ischemic attack is caused by a
temporary interruption of blood flow in an area of
the brain. Unlike in a true stroke, normal brain
function will return with 24 hours.

pressure. In particular, eating a healthy diet and not
smoking to maintain proper blood pressure will help
prevent damaging strokes. Although it is impossible to
predict head trauma, the use of head protection while
participating in dangerous sports or activities can
reduce the risk of serious brain damage.
Resources
BOOKS

These include out-put focused therapy (stimulationresponse), psycholinguistic therapy (cognitive), cognitive neurorehabilitation, and combinations thereof.
Although these treatments approach aphasia differently, they all share a common thread by identifying
the specific communication deficits and then targeting
them with various modalities (computer-aided therapy, picture cards, reading and writing exercises,
speech practice, etc.). These techniques stimulate
the various parts of the brain associated with language, memory, and understanding, and thus allow it
to heal.

Prognosis
Fortunately, about half of patients will suffer
from transient dysphasia, in which the symptoms
fade completely after only a few days. However, a
patient’s prognosis will greatly depend on several
factors, such as the location and extent of the
underlying damage. Additional factors of importance are the patient’s age, general health, and
mental health and motivation. Handedness may
also be an indicator for recovery, as left-handed
individuals have language centers located in both
hemispheres of the brain (not just the left). As
such, left-handed patients have access to language
skills from either side of the brain, which can
expedite their recovery. Even with therapy, dysphasia may take several years to overcome. Indeed,
some patients will never regain their pre-trauma
skill level of communication and speech.

Brookshire, R. Introduction to Neurogenic Communication
Disorders (6th edition) St. Louis, MO: Mosby, 2003.
Darley, F. Aphasia. Philadelphia, PA: WB Saunders, 1982.
Newman, S., and R. Epstein (eds). Current Perspectives in
Dysphasia. New York: Churchill Livingstone, 1985.
PERIODICALS

Albert, M.L.. ‘‘Treatment of Aphasia.’’ Archives of
Neurology 55 (November, 1998): 1417-1419.
ORGANIZATIONS

National Aphasia Association. 29 John Street, Suite 1103,
New York, NY 21108. (800) 922-4622. <http://
www.aphasia.org>.
Speakability. 1 Royal Street, London, UK SE1 7LL.
020-7261-9572. <http://www.speakability.org.uk/>.
OTHER

‘‘Aphasia.’’ The Merck Manual (Section 14. Neurologic
Disorders)<http://www.merck.com/mrkshared/
mmanual/section14/chapter169/169b.jsp>.
‘‘Aphasia.’’ National Institute on Deafness and Other
Communication Disorders<http://www.nidcd.nih.gov/
health/voice/aphasia.asp>.
‘‘CMSD 336 Neuropathologies of Language and
Cognition.’’ The Neuroscience on the Web
Series<http://www.csuchico.edu/pmccaff/syllabi/
SPPA336/336unit5.html>.

Jason Fryer

Dysphasia see Aphasia
Dyspnea see Shortness of breath
Dysthymic disorder see Depressive disorders
Dystonia see Movement disorders

Prevention
Dysphasia can be prevented by avoiding the
causes of brain injury and stroke, such as high blood

GALE ENCYCLOPEDIA OF MEDICINE

1237

Dysphasia

KEY TERMS

E
Description

E. coli see Escherichia coli
E. coli infection see Enterobacterial
infections
E. coli O157:H7 infection see Escherichia
coli
Ear canal infection see Otitis externa

I Ear exam with an otoscope
Definition
An otoscope is a hand-held instrument with a tiny
light and a cone-shaped attachment called an ear speculum, which is used to examine the ear canal. An ear
examination is a normal part of most physical examinations by a doctor or nurse. It is also done when an
ear infection or other type of ear problem is suspected.

Purpose
An otoscope is used to look into the ear canal to
see the ear drum. Redness or fluid in the eardrum can
indicate an ear infection. Some otoscopes can deliver a
small puff of air to the eardrum to see if the eardrum
will vibrate (which is normal). This type of ear examination with an otoscope can also detect a build up of
wax in the ear canal, or a rupture or puncture of the
eardrum.

Precautions
No special precautions are required. However, if
an ear infection is present, an ear examination may
cause some discomfort or pain.
GALE ENCYCLOPEDIA OF MEDICINE

An ear examination with an otoscope is usually
done by a doctor or a nurse as part of a complete physical
examination. The ears may also be examined if an ear
infection is suspected due to fever, ear pain, or hearing
loss. The patient will often be asked to tip the head
slightly toward the shoulder so the ear to be examined
is pointing up. The doctor or nurse may hold the ear lobe
as the speculum is inserted into the ear, and may adjust
the position of the otoscope to get a better view of the ear
canal and eardrum. Both ears are usually examined,
even if there seems to be a problem with just one ear.

Preparation
No special preparation is required prior to an ear
examination with an otoscope. The ear speculum,
which is inserted into the ear, is cleaned and sanitized
before it is used. The speculums come in various sizes,
and the doctor or nurse will select the size that will be
most comfortable for the patient’s ear.

Aftercare
If an ear infection is diagnosed, the patient may
require treatment with antibiotics. If there is a buildup
of wax in the ear canal, it might be rinsed or scraped out.

Risks
This type of ear examination is simple and generally
harmless. Caution should always be used any time an
object is inserted into the ear. This process could irritate
an infected external ear canal and could rupture an eardrum if performed improperly or if the patient moves.

Normal results
The ear canal is normally skin-colored and is
covered with tiny hairs. It is normal for the ear canal
to have some yellowish-brown earwax. The eardrum is
1239

Ear surgery

KEY TERMS
Ear speculum—A cone- or funnel-shaped attachment for an otoscope which is inserted into the ear
canal to examine the eardrum.
Otoscope—A hand-held instrument with a tiny
light and a funnel-shaped attachment called an
ear speculum, which is used to examine the ear
canal and eardrum.

deformities of the ear’s auditory tube, middle ear,
inner ear, and auditory and vestibular systems. Ear
surgery is commonly performed to treat conductive
hearing loss, persistent ear infections, unhealed perforated eardrums, congenital ear defects, and tumors.
Ear surgery is performed on children and adults.
In some cases, surgery is the only treatment; in others,
it is used only when more conservative medical treatment fails.

Precautions
typically thin, shiny, and pearly-white to light gray in
color. The tiny bones in the middle ear can be seen
pushing on the eardrum membrane like tent poles. The
light from the otoscope will reflect off of the surface of
the ear drum.

Abnormal results
An ear infection will cause the eardrum to look
red and swollen. In cases where the eardrum has
ruptured, there may be fluid draining from the middle
ear. A doctor may also see scarring, retraction of the
eardrum, or bulging of the eardrum.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
Ear Foundation. 1817 Patterson St., Nashville, TN 37203.
(800) 545-4327. <http://www.earfoundation.org>.
OTHER

‘‘Ear Test.’’ HealthAnswers.com. <http://
www.healthanswers.com>.

Altha Roberts Edgren

I Ear surgery

The precautions vary, depending on the type of ear
surgery under consideration. For example, stapedectomy (removal of parts of the middle ear and insertion of
prosthesis parts) should not be performed on people
with external or middle ear infection or inner ear disease. For people with complete hearing loss in the other
ear, it should be performed cautiously. Microsurgery
for the removal of a cholesteatoma (a cyst-like mass of
cells in the middle ear) should not be performed on
patients who are extremely ill or have other medical
conditions. Tympanoplasty (any surgical procedure on
the eardrum or middle ear) should not be performed on
patients with chronic sinus or nasal problems or with
medical problems such as poorly controlled diabetes
and heart disease. Surgery for congenital microtia and
atresia (abscense of normal bodily openings, such as
the outer ear canal) should not be performed if the
middle ear space is totally or almost totally absent.

Description
Most ear surgery is microsurgery, performed with
an operating microscope to enable the surgeon to view
the very small structures of the ear. The use of minimally invasive laser surgery for middle ear procedures
is growing. Laser surgery reduces the amount of
trauma due to vibration, enhances coagulation, and
enables surgeons to access hard to reach places in the
middle ear. Laser surgery can be performed in an
office operating suite. Types of ear surgery include
stapedectomy, tympanoplasty, myringotomy and ear
tube surgery, ear surgery to repair a perforated
eardrum, cochlear implants, and tumor removal.

Definition
Ear surgery is the treatment of diseases, injuries, or
deformations of the ear by operation with instruments.

Purpose
Ear surgery is performed to correct certain types
of hearing loss, and to treat diseases of, injuries to, or
1240

Stapedectomy
To restore hearing loss, which is usually due to
otosclerosis, stapedectomy is performed. Stapedectomy
is the removal of all or part of the stapes, one of the
bones in the middle ear, and replacement with a tiny
prosthesis. An incision is made in the middle ear,
the small bones are identified, and the stapes is
GALE ENCYCLOPEDIA OF MEDICINE

Ear surgery

removed. The stainless steel wire and cellulose sponge
prosthesis is inserted, blood and fluid are drained,
and the wound is closed. Performed in a hospital or
outpatient surgical facility under local or general
anesthetic, full recovery takes about three weeks but
hearing should improve immediately.
Tympanoplasty
Tympanoplasty is performed to reconstruct the
eardrum after partial or total conductive hearing
loss, usually caused by chronic middle ear infections,
or perforations that do not heal. This is usually a same
day surgery, performed under either local or general
anesthesia. After making an incision in the ear to view
the perforation, the ear drum is elevated away from
the ear canal and lifted forward. If the bones of hearing (ossicular chain) are functioning, tissue is taken
from the ear and grafted to the eardrum to close the
perforation. A thin sheet of silastic and Gelfoam hold
the graft in place. The ear is stitched together, and a
sterile patch is placed on the outside of the ear canal.
Tympanoplasty is successful in over 90% of all cases.
The need for ossicular reconstruction (reconstruction
of tiny bones of the middle ear) is sometimes known
before surgery and even when identified during
surgery, can usually be done while reconstructing the
eardrum. If the gap between the anvil bone and the
stapes is small, a small piece of bone or cartilage from
the patient can be inserted; if is is large, the incus bone
is removed, modelled into a prosthesis, and reinserted
between the stapes and the malleus. Reconstruction
could also be achieved by inserting a strut made from
artificial bone. For tympanoplasty with ossicular
reconstruction, the patient usually stays in the hospital
overnight. The recovery period is about four weeks.
Myringotomy and ear tube surgery
Myringotomy and ear tube surgery is performed
to drain ear fluid and prevent ear infections when
antibiotics don’t work or when ear infections are
chronic. The process normalizes pressure in the middle
ear and decreases fluid accumulation. It is most
commonly performed on infants and children, in
whom ear infections are most frequent, and may be
done on one or both ears. The surgeon makes a small
hole in the ear drum, then uses suction to remove fluid.
A small ear tube of metal or plastic is inserted into the
ear drum to allow continual drainage. The tube
prevents infections as long as it stays in place, which
varies from six months to three years. When the tube
falls out, the hole grows over. As many of 25% of
children under the age of two who need ear tubes
may need them again. Myringotomy and ear tube
GALE ENCYCLOPEDIA OF MEDICINE

Microsurgery being performed in the inner ear. (Photograph by
Hans Halberstadt, Photo Researchers, Inc. Reproduced by
permission.)

surgery is performed in a hospital, using a general
anesthetic for most children and a local anesthetic
for older children or adults. No anesthetic may be
used for infants. The procedure usually takes about
two hours. Most patients can go home the same day;
children under three years of age and those with
chronic diseases usually stay overnight.
Ear surgery for a perforated eardrum
Ear surgery for a perforated eardrum is only
performed in rare cases where it does not heal on its
own. In most cases, this is performed in a surgeon’s
office using a topical anesthetic. The surgeon scratches
the undersurface of the eardrum, stimulating the skin
to heal and the eardrum to close. A thin patch placed
on the eardrum’s outer surface allows the skin under
the eardrum to heal.
Cochlear implants
Cochlear implants stimulate nerve ends within the
inner ear, enabling deaf children to hear. The device has
a microphone that remains outside the ear, a processor
that selects and codes speech sounds, and a receiver/
stimulator to convert the coded sounds to electric
signals that stimulate the hearing nerve and are recognized by the brain as sound. During surgery, an incision
is made behind and slightly above the ear. A circular
hole is drilled in the bone to receive the device’s internal
coil. The mastoid bone leading to the middle ear is
opened to receive the electrodes. The internal coil is
inserted and secured, followed by the electrodes. The
wound is stitched up and when it heals, an external unit
comprised of a stimulator with a microphone is worn
behind the ear. Performed in a hospital under general
anesthesia, the operation takes about two hours and
1241

Ear surgery

usually requires a hospital stay overnight. The patient
can resume normal activities in two to three weeks.
Ear surgery for tumors
Some ear tumors can be very serious and should
be removed surgically. For a tumor on the skin of the
ear canal, the skin is removed surgically, the bone
beneath it is drilled away and a skin graft is placed in
the ear canal. If the tumor is near the eardrum, the skin
of the ear canal and the eardrum are removed along
with the bone surrounding the ear canal. A skin graft is
placed on the bare bone. For basal cell cancers and low
grade glandular malignancies, surgical resection of the
ear canal is adequate. Squamous cell carcinoma, a
serious form of cancer, of the external ear canal
requires radical surgery, followed by radiation therapy. Cholesteatoma, a benign tumor caused by an
infection in a perforated eardrum that did not heal
properly and can destroy the bones of hearing, is
removed with microsurgery. Mastoidectomy is performed for mastoiditis, an inflammation of the middle
ear, if medical therapy does not work. Petrous apicectomy is performed to drain the petrous apicitis, the
bone between the middle ear and the clivis.
Ear surgery for congenital ear defects
Congenital atresia, the absence of the external ear
canal, and congenital microtia, abnormal growth of
the external ear, often occur together, although atresia
can occur without microtia. Surgery to reconstruct the
ear usually takes place when the child is four or five
years old and may require several operations. A facial
plastic surgeon and an ear surgeon work together,
repairing the microtia first and then the atresia.
During surgery, a bony opening is created over the
bones of hearing. The surfaces of the bony ear
canal are then relined with a skin graft from the
thigh or abdomen. Tissue from behind the eardrum
is used to create a new eardrum. In many cases, the
middle ear will also need to be reconstructed. Surgery
is performed in a hospital under general anesthesia.
Other types of ear surgery
Surgery may also be appropriate to remove multiple
bony overgrowths of the ear canal or in rare cases of
compromised auditory tube function, to narrow the tube.

Preparation
The preparation depends upon the type of ear
surgery performed. For many procedures, blood and
urine studies and hearing tests are conducted.
1242

KEY TERMS
Auditory—Relating to the sense of the organs of
hearing.
Cholesteatoma—A cystic mass of cells in the middle ear, occurring as a congential defect or as a
serious complication of a disease or traumtic condition of the ear.
Otologic—Relating to the study, diagnosis, and
treatment of diseases of the ear and related
structures.

Aftercare
The type of aftercare depends upon the type of
surgery performed. In most cases, the ear(s) should be
kept dry and warm. Non-prescription drugs such as
acetaminophen can be used for pain.

Risks
The type of risk depends on the type of surgery
performed. Total hearing loss is rare.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
American Hearing Research Foundation. 55 E. Washington
St., Suite 2022, Chicago, IL 60602. (312) 726-9670.
<http://www.american-hearing.org/>.
American Speech-Language-Hearing Association. 10801
Rockville Pike, Rockville, MD 20852. (800) 638-8255.
<http://www.asha.org>.

Lori De Milto

Ear tubes see Myringotomy and ear tubes
Ear wax impaction see Cerumen impaction
Eardrum perforation see Perforated eardrum
Eastern equine encephalitis see Arbovirus
encephalitis
Eating disorders see Anorexia nervosa;
Bulimia nervosa
Eaton agent pneumonia see Mycoplasma
infections
Ebola virus infection see Hemorrhagic fevers
GALE ENCYCLOPEDIA OF MEDICINE

ECG see Electrocardiography

I Echinacea
Definition
Echinacea, or purple coneflower, is a perennial
herb of the Composite family, commonly known as
the daisy family. Most often referred to as the purple
coneflower, this hardy plant also known as Sampson
root, Missouri snakeroot, and rudbeckia. The prominent, bristly seed head inspired the generic name of the
plant, taken from the Greek word echinos meaning
hedgehog.

Description
Echinacea is a North American prairie native,
abundant in the Mid-west, and cultivated widely in
ornamental and medicinal gardens. The purple-pink
rays of the blossom droop downward from a brassy
hued center cone composed of many small, tubular
florets. The conspicuous flowers bloom singly on
stout, prickly stems from mid-summer to autumn.
Flower heads may grow to 4 in (10.16 cm) across.
The dark green leaves are opposite, entire, lanceolate,
toothed, and hairy with three prominent veins. The
narrow upper leaves are attached to the stem with
stalks. The lower leaves are longer, emerging from
the stem without a leaf stalk, and growing to 8 in
(20.32 cm) in length. The plant develops deep, slender,
black roots. Echinacea propagates easily from seed or
by root cuttings. However, due to its increasing
popularity as an herbal supplement, echinacea is
numbered among the 19 medicinal plants considered
at risk by the Vermont nonprofit organization, United
Plant Savers.

Purpose
Three species of echinacea are useful medicinally:
Echinacea augustifolia, Echinacea purpurea, and
Echinacea pallida. The entire plant has numerous
medicinal properties that act synergistically to good
effect. Echinacea is most often used to boost the
immune system and fight infection. Research has
shown that echinacea increases production of interferon in the body. It is antiseptic and antimicrobial,
with properties that act to increase the number of
white blood cells available to destroy bacteria and
GALE ENCYCLOPEDIA OF MEDICINE

slow the spread of infection. As a depurative, the
herbal extract cleanses and purifies the bloodstream,
and has been used effectively to treat boils. Echinacea
is vulnerary, promoting wound healing through the
action of a chemical substance in the root known as
caffeic acid glycoside. As an alterative and an
immuno-modulator, echinacea acts gradually to promote beneficial change in the entire system. It has also
been used to treat urinary infection and Candida
albicans infections. Echinacea is a febrifuge, useful in
reducing fevers. It is also useful in the treatment of
hemorrhoids. A tincture, or a strong decoction of
echinacea serves as an effective mouthwash for the
treatment of pyorrhea and gingivitis.
Native American plains Indians relied on echinacea as an all-purpose antiseptic. The Sioux tribe
valued the root as a remedy for snake bite, the
Cheyenne tribe chewed the root to quench thirst, and
another tribe washed their hands in a decoction of
echinacea to increase their tolerance of heat.
European settlers learned of the North American
herb’s many uses, and soon numerous echinaceabased remedies were commercially available from
pharmaceutical companies in the United States.
Echinacea was a popular remedy in the United States
through the 1930s. It was among many medicinal
herbs listed in the U.S. Pharmacopoeia, the official
United States government listing of pharmaceutical
raw materials and recipes. The herb fell out of popular
use in the United States with the availability of
antibiotics. In West Germany, over 200 preparations
are made from the species E. purpurea. Commercially
prepared salves, tinctures, teas, and extracts are
marketed using standardized extracts. Echinacea is
regaining its status in the United States as a household
medicine-chest staple in many homes. It is one of the
best-selling herbal supplements in United States
health food stores.
Clinical studies have found that the entire plant
possesses medicinal properties with varying levels of
effectiveness. Echinacea is of particular benefit in the
treatment of upper respiratory tract infections. Some
research has shown that echinacea activates the
macrophages that destroy cancer cells and pathogens.
When taken after cancer treatments, an extract of the
root has been found to increase the body’s production
of white blood cells. Echinacea has been shown to be
most effective when taken at the first sign of illness,
rather than when used as a daily preventative. Other
research has demonstrated the significant effect of
E. purpurea root on reducing the duration and severity
of colds and flu. Some herbal references list only
the root as the medicinal part, others include the
1243

Echinacea

Ecchymosis see Bruises

Echinacea

aerial parts of the plant, particularly the leaf. Research
studies in Europe and the United States have
concluded that the entire plant is medicinally effective.
Most research has been done on the species E. pallida
and E. purpurea. All three species of echinacea are
rich in vitamins and minerals. Echinacea is an herbal
source of niacin, chromium, iron, manganese,
selenium, silicon, and zinc.

Preparations
The quality of any herbal supplement depends
greatly on the conditions of weather and soil where
the herb was grown, the timing and care in harvesting,
and the manner of preparation and storage.
Decoction is the best method to extract the
mineral salts and other healing components from the
coarser herb materials, such as the root, bark, and
stems. It is prepared by adding 1 oz (28.4 g) of the
dried plant materials, or 2 oz (56.7 g) of fresh plant
parts, to 1 pt (0.47 l) of pure, unchlorinated, boiled
water in a non-metallic pot. Simmer for about one
half hour. Strain and cover. A decoction may be
refrigerated for up to two days and retain its healing
qualities.
An infusion is the method used to derive benefits
from the leaves, flowers, and stems in the form of an
herbal tea. Use twice as much fresh, chopped herb
as dried herb. Steep in 1 pt (0.47 l) of boiled, unchlorinated water for 10–15 minutes. Strain and cover.
Drink warm, sweetened with honey if desired. A
standard dose is three cups per day. An infusion will
keep for up to two days in the refrigerator and retain
its healing qualities.
A tincture is the usual method to prepare a
concentrated form of the herbal remedy. Tinctures,
properly prepared and stored, will retain medicinal
potency for two years or more. Combine 4 oz (114 g)
of finely cut fresh or powdered dry herb with 1 pt
(0.47 l) of brandy, gin, or vodka in a glass container.
The alcohol should be enough to cover the plant
parts and have a 50/50 ratio of alcohol to water.
Place the mixture away from light for about two
weeks, shaking several times each day. Strain and
store in a tightly capped, dark glass bottle. A
standard dose is 0.14 oz (4 ml) of the tincture three
times a day.

KEY TERMS
Alterative—A medicinal substance that acts
gradually to nourish and improve the system.
Antimicrobial—A plant substance that acts to
inhibit the growth of harmful microorganisms, or
acts to destroy them.
Febrifuge—A plant substance that acts to prevent
or reduce fever.
Glycoside—An herbal carbohydrate that exerts
powerful effect on hormone-producing tissues.
The glycoside breaks down into a sugar and a
non-sugar component.
Lanceolate—Narrow, leaf shape that is longer than
it is wide, and pointed at the end.
Macrophage—Specialized cells present throughout
the lymphoid tissues of the body that circulate in the
bloodstream. Macrophages have a surface marker
that stimulates other cells to react to an antigen.

Because the plant has proven immuno-modulating
properties, individuals with systemic lupus erythmatosus, rheumatoid arthritis, tuberculosis, leukemia,
multiple sclerosis, or AIDS should consult their
physician before using echinacea. Echinacea should
not be given to children under two years of age, and
it should only be given to children over two in
consultation with a physician. Research indicates
that echinacea is most effective when taken at first
onset of symptoms of cold or flu, and when usage
is continued no longer than eight weeks. There is
some indication that the herb loses its effectiveness
when used over a long period of time. It is necessary
to interrupt use for a minimum of several weeks
in order to give the body’s immune system the opportunity to rest and adjust.

Side effects
No side effects are reported with oral administration of echinacea, either in tincture, capsule, or as a
tea, when taken according to recommended doses.
Chills, fever, and allergic reactions have been reported
in some research studies using an injection of the plant
extract.

Precautions
Echinacea is considered safe in recommended
doses. Pregnant or lactating women, however, are
advised not to take echinacea in injection form.
1244

Interactions
None reported. When used in combination with
other herbs, dosage should be lowered.
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Deneen, Sally, and Tracey C. Rembert. ‘‘StalkingMedicinal
Plants, An International Trade Imperils Wild Herbs.’’
E Magazine July-August 1999.
OTHER

Herb World News Online, Research Reviews. Herb Research
Foundation. 1999. <http://www.herbs.org>.

Clare Hanrahan

I Echinococcosis
Definition
Echinococcosis (Hydatid disease) refers to human
infection by the immature (larval) form of tapeworm,
Echinococcus. One of three forms of the Echinococcus
spp., E. granulosus, lives on dogs and livestock, and
infects humans through contact with these animals.
Allergic reactions and damage to various organs
from cyst formation are the most common forms of
disease in humans.

Description
E. granulosus is found in many areas of Africa,
China, South America, Australia, New Zealand, and
Mediterranean and eastern Europe, as well as in parts
of the western United States. The parasite lives in
regions where dogs and livestock cohabitate. Direct
exposure to infectious dogs, as well as parasitic eggs
released into the environment during shedding, are
both sources of human infection.
In humans, cysts containing the larvae develop
after ingestion of eggs. Cysts form primarily in the
lungs and liver. Cysts developing in the liver are
responsible for about two-thirds of echinococcosis
cases. Echinococcosis is a significant public health problem in many areas of the world, but control programs
have decreased the rate of infection in some regions.
In Kenya alone, the numbers of persons infected
each year is as high as 220 per 100,000 population.

Causes and symptoms
After ingestion, the eggs develop into embryos
within the intestines and then travel to the liver and
lungs through major blood vessels. The embryos then
begin to form cysts within the liver and lungs, causing
GALE ENCYCLOPEDIA OF MEDICINE

damage as they enlarge over a period of five to 20
years. Cysts may become over 8 in (20.3 cm) or more
in size and contain a huge amount of highly allergenic
fluid. Studies show that while the liver is most often
targeted, lungs, brain, heart, and bone can also be
affected.
The major symptoms are due to compression
damage, blockage of vessels and ducts (such as the
bile ducts), and leakage of fluid from cysts. The following symptoms are frequent.


Liver involvement causes pain and eventually jaundice or cholangitis due to blockage of bile ducts.
Infection of cysts leads to abscesses in up to 20%.



Lung cysts cause cough and chest pain.



Bone cysts cause fractures and damage to bone tissue.



Heart involvement leads to irregularities of heart
beat and inflammation of the covering of the heart
(pericardium).



Allergic reactions occur from leakage of cyst fluid
that contains antigens. Itching, fever, and rashes are
frequent, and fatal allergic reactions (anaphylaxis)
have been reported. Eosinophils, which are blood
cells involved in allergic reactions, are increased in
many patients.

Diagnosis
X rays, computed tomography scans (CT scans),
and ultrasound are very helpful in detecting cysts.
Some cysts will develop characteristic hardening of
organ tissues from calcium deposits (calcifications).
Blood tests to detect antibodies are useful when
positive, but up to 50% of patients have negative
results. Examination of aspirated cyst fluid for
parasites can be diagnostic, but carries the danger of
a fatal allergic reaction. Treatment with anti-parasitic
medications before aspiration is reported to decrease
allergic complications and decrease the risk of spread
during the procedure.

Treatment
Treatment depends on the size and location of
cysts, as well as the symptoms they are producing.
Surgical removal of cysts and/or surrounding tissue
is the accepted method of treatment, but carries a risk
of cyst rupture with spread or allergic reactions.
Recent studies using medication alongside aspiration
and drainage of cysts instead of surgery are very
encouraging.
The medication albenzadole can be taken before
or after surgery or alone without surgery. However, its
1245

Echinococcosis

Resources

Echocardiography

Uterus with eggs

Sucker

Echinococcus granulosus
Infection with the larva of Echinococcus granulosus (shown above) is responsible for the disease echinococcosis. (Illustration by
Electronic Illustrators Group.)

Prevention

KEY TERMS
Allergenic—A substance capable of causing an
allergic reaction.
Cholangitis—Infection or inflammation of the bile
ducts; often causes abdominal pain, fever, and
jaundice.
Computed tomography (CT) scan—A specialized
x-ray procedure in which cross-sections of the area
in question can be examined in detail.
Cyst—A protective sac that includes either fluid or
the cell of an organism. The cyst enables many
organisms to survive in the environment for long
periods of time without need for food or water.
Embryo—The very beginning stages of development of an organism.
Jaundice—The yellow-greenish coloring of the skin
and eyes due to the presence of bile pigments. The
presence of jaundice is usually, but not always, a
sign of liver disease.
Tapeworm—An intestinal parasite that attaches to
the intestine or travels to other organs such as the
liver and lungs.
Ultrasound—A noninvasive procedure based on
changes in sound waves of a frequency that cannot
be heard, but respond to changes in tissue
composition.

effectiveness as a single treatment is still not known.
Multiple courses of medication are often necessary,
with cure rates of only about 30%. Response to
treatment is best monitored by serial CT scans or
similar x-ray studies.
1246

Good hand washing, treating infected dogs, and
preventing dogs’ access to slaughter houses discourage
spread of the disease. Limiting the population of stray
dogs has also been helpful.
Resources
OTHER

‘‘Percutaneous Drainage Compared with Surgery for
HepaticHydatid Cysts.’’ New England Journal of
Medicine Online. <http://content.nejm.org>.

David Kaminstein, MD

Echinococcus granulosus infection see
Echinococcosis

I Echocardiography
Definition
Echocardiography is a diagnostic test that uses
ultrasound waves to create an image of the heart
muscle. Ultrasound waves that rebound or echo off
the heart can show the size, shape, and movement of
the heart’s valves and chambers as well as the flow of
blood through the heart. Echocardiography may show
such abnormalities as poorly functioning heart valves
or damage to the heart tissue from a past heart attack.

Purpose
Echocardiography is used to diagnose certain
cardiovascular diseases. In fact, it is one of the most
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Echocardiography is an extremely safe procedure
and no special precautions are required.

Description
Echocardiography creates an image of the heart
using ultra-high-frequency sound waves–sound waves
that are too high in frequency to be heard by the
human ear. The technique is very similar to ultrasound
scanning commonly used to visualize the fetus during
pregnancy.
An echocardiography examination generally lasts
between 15–30 minutes. The patient lies bare-chested
on an examination table. A special gel is spread over
the chest to help the transducer make good contact
and slide smoothly over the skin. The transducer, a
small hand-held device at the end of a flexible cable,
is placed against the chest. Essentially a modified
microphone, the transducer directs ultrasound waves
into the chest. Some of the waves get echoed (or
reflected) back to the transducer. Since different
tissues and blood all reflect ultrasound waves differently, these sound waves can be translated into a
meaningful image of the heart, which can be displayed
on a monitor or recorded on paper or tape. The
patient does not feel the sound waves, and the entire
procedure is painless. In fact, there are no known
side effects.
Occasionally, variations of the echocardiography
test are used. For example, Doppler echocardiography
GALE ENCYCLOPEDIA OF MEDICINE

Echocardiography

widely used diagnostic tests for heart disease. It can
provide a wealth of helpful information, including
the size and shape of the heart, its pumping strength,
and the location and extent of any damage to its
tissues. It is especially useful for assessing diseases of
the heart valves. It not only allows doctors to evaluate
the heart valves, but it can detect abnormalities in the
pattern of blood flow, such as the backward flow of
blood through partly closed heart valves, known as
regurgitation. By assessing the motion of the heart
wall, echocardiography can help detect the presence
and assess the severity of coronary artery disease, as
well as help determine whether any chest pain is related
to heart disease. Echocardiography can also help
detect hypertrophic cardiomyopathy, in which the
walls of the heart thicken in an attempt to compensate
for heart muscle weakness. The biggest advantage to
echocardiography is that it is noninvasive (does not
involve breaking the skin or entering body cavities)
and has no known risks or side effects.

A patient getting an EKG. (Photo Researchers. Reproduced by
permission.)

employs a special microphone that allows technicians
to measure and analyze the direction and speed of
blood flow through blood vessels and heart valves.
This makes it especially useful for detecting and
evaluating regurgitation through the heart valves. By
assessing the speed of blood flow at different locations
around an obstruction, it can also help to precisely
locate the obstruction.
An exercise echocardiogram is an echocardiogram performed during exercise, when the heart
muscle must work harder to supply blood to the
body. This allows doctors to detect heart problems
that might not be evident when the body is at rest
and needs less blood. For patients who are unable to
exercise, certain drugs can be used to mimic the effects
of exercise by dilating the blood vessels and making
the heart beat faster.

Preparation
The patient removes any clothing and jewelry
above the chest.

Aftercare
No special measures need to be taken following
echocardiography.

Risks
There are no known risks associated with the use
of echocardiography.

Normal results
A normal echocardiogram shows a normal heart
structure and the normal flow of blood through the
1247

Ectopic pregnancy

I Ectopic pregnancy

KEY TERMS
Noninvasive—Pertaining to a diagnostic procedure
or treatment that does not require the skin to be
broken or a body cavity to be entered.
Regurgitation—Backward flow of blood through a
partly closed heart valve.
Transducer—A device that converts electrical signals into ultrasound waves and ultrasound waves
back into electrical impulses.
Ultrasound—Sound waves at a frequency of over
20,000 kHz, often used for diagnostic imaging.

heart chambers and heart valves. However, a normal
echocardiogram does not rule out the possibility of
heart disease.

Abnormal results
An echocardiogram may show a number of
abnormalities in the structure and function of the
heart, such as:


thickening of the wall of the heart muscle (especially
the left ventricle)



abnormal motion of the heart muscle



blood leaking backward through the heart valves
(regurgitation)



decreased blood flow through a heart valve (stenosis)

Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Robert Scott Dinsmoor

Echovirus infections see Enterovirus
infections
Eclampsia see Preeclampsia and eclampsia
ECT see Electroconvulsive therapy
Ectopic orifice of the ureter see Congenital
ureter anomalies
1248

Definition
In an ectopic pregnancy, the fertilized egg implants
in a location outside the uterus and tries to develop
there. The word ectopic means ‘‘in an abnormal place
or position.’’ The most common site is the fallopian
tube, the tube that normally carries eggs from the ovary
to the uterus. However, ectopic pregnancy can also
occur in the ovary, the abdomen, and the cervical
canal (the opening from the uterus to the vaginal
canal). The phrases tubal pregnancy, ovarian pregnancy, cervical pregnancy, and abdominal pregnancy
refer to the specific area of an ectopic pregnancy.

Description
Once a month, an egg is produced in a woman’s
ovary and travels down the fallopian tube where it
meets the male’s sperm and is fertilized. In a normal
pregnancy the fertilized egg, or zygote, continues on its
passage down the fallopian tube and enters the uterus
in three to five days. The zygote continues to grow,
implanting itself securely in the wall of the uterus. The
zygote’s cells develop into the embryo (the organism in
its first two months of development) and placenta
(a spongy structure that lines the uterus and nourishes
the developing organism).
In a tubal ectopic pregnancy, the fertilized egg
cannot make it all the way down the tube because of
scarring or obstruction. The fallopian tube is too narrow for the growing zygote. Eventually the thin walls of
the tube stretch and may burst (rupture), resulting in
severe bleeding and possibly the death of the mother.
More than 95% percent of all ectopic pregnancies occur
in the fallopian tube. Only 1.5% develop in the abdomen; less than 1% develop in the ovary or the cervix.

Causes and symptoms
As many as 50% of women with ectopic pregnancies have a history of pelvic inflammatory disease
(PID). This is an infection of the fallopian tubes
(salpingitis) that can spread to the uterus or ovaries.
It is most commonly caused by the organisms
Gonorrhea and Chlamydia and is usually transmitted
by sexual intercourse.
Other conditions also increase the risk of ectopic
pregnancy. They include:


Endometriosis. A condition in which the tissue that
normally lines the uterus is found outside the uterus,
and can block a fallopian tube.
GALE ENCYCLOPEDIA OF MEDICINE







Exposure to diethylsilbestrol (DES) as a fetus. If a
woman’s mother took DES (a synthetic version of
the hormone estrogen) during pregnancy, the woman
may have abnormalities in her fallopian tubes that
can make ectopic pregnancy more likely.
Taking hormones. Estrogen and progesterone are
hormones that regulate the menstrual cycle and may
be in medications prescribed by a doctor for birth
control or other reasons. Taking these hormones can
affect the interior lining of the fallopian tubes and
slow the movement of the fertilized egg down the
tube. Women who become pregnant in spite of taking
some progesterone-only contraceptives have a greater
chance of an ectopic pregnancy. Ectopic pregnancy is
also more likely when the ovaries are artificially
stimulated with hormones to produce eggs for in
vitro fertilization (a procedure in which eggs are
taken from a woman’s body, fertilized, and then
placed in the uterus in an attempt to conceive a child).
Use of an intrauterine device (IUD). These contraceptive devices are designed to prevent fertilized eggs
from becoming implanted in the uterus, but they
have only a minimal effect on preventing ectopic
pregnancies. Therefore, if a woman becomes pregnant while using an IUD for contraception, the fertilized egg is more likely to be implanted someplace
other than the uterus. For example, among women
who become pregnant while using a progesteronebearing IUD, about 15% have ectopic pregnancies.
Surgery on a fallopian tube. The risk of ectopic
pregnancy can be as high as 60% after undergoing
elective tubal sterilization, a procedure in which the
fallopian tubes are severed to prevent pregnancy.
Women who have successful surgery to reverse the
procedure are also more likely to have an ectopic
pregnancy.
Early symptoms

In an ectopic pregnancy all the hormonal changes
associated with a normal pregnancy may occur. The
early symptoms include: fatigue; nausea; a missed period; breast tenderness; low back pain; mild cramping
on one side of the pelvis; and abnormal vaginal bleeding, usually spotting.
Later symptoms
As the embryo grows too large for the confined
space in the tube, the first sign that something is wrong
may be a stabbing pain in the pelvis or abdomen. If the
tube has ruptured, blood may irritate the diaphragm
and cause shoulder pain. Other warning signs are
lightheadedness and fainting.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
To confirm an early diagnosis of ectopic pregnancy, the doctor must determine first that the patient
is pregnant and that the location of the embryo is
outside the uterus. If an ectopic pregnancy is suspected, the doctor will perform a pelvic examination
to locate the source of pain and to detect a mass in the
abdomen.
Several laboratory tests of the patient’s blood
provide information for diagnosis. Measurement of
the human chorionic gonadotropin (hCG) level in
the patient’s blood serum is the most useful laboratory
test in the early stages. In a normal pregnancy, the
level of this hormone doubles about every two days
during the first 10 weeks. In an ectopic pregnancy, the
rate of the increase is much slower and the low hCG
for the stage of the pregnancy is a strong indication
that the pregnancy is abnormal. (It could also represent a miscarriage in progress.) The level is usually
tested several times over a period of days to determine
whether or not it is increasing at a normal rate.
Progesterone levels in the blood are also measured. Lower than expected levels can indicate that
the pregnancy is not normal.
An ultrasound examination may provide information about whether or not the pregnancy is ectopic. A
device called a transducer, which emits high frequency
sound waves, is moved over the surface of the patient’s
abdomen or inserted into the vagina. The sound waves
bounce off of the internal organs and create an image
on a screen. The doctor should be able to see whether
or not there is a fetus developing in the uterus after
at least five weeks of gestation. Before that point, a
normal pregnancy is too small to see.
A culdocentesis may also help confirm a diagnosis. In this procedure a needle is inserted into the space
at the top of the vagina, behind the uterus and in front
of the rectum. Blood in this area may indicate bleeding
from a ruptured fallopian tube.
A laparoscopy will enable the doctor to see the
patient’s reproductive organs and examine an ectopic
pregnancy. In this technique, a hollow tube with a
light on one end is inserted through a small incision
in the abdomen. Through this instrument the internal
organs can be observed.

Treatment
Ectopic pregnancy requires immediate treatment.
The earlier the condition is treated, the better the
chance to preserve the fallopian tube intact for future
normal pregnancies.
1249

Ectopic pregnancy



Ectopic pregnancy

KEY TERMS

Embryo

Embryo—In humans, the developing organism
from conception until approximately the end of
the second month.
Fallopian tube—The tube that carries the egg from
the ovary to the uterus.
Ovary

Uterus

Fallopian tube

Vagina

In an ectopic pregnancy, the fertilized egg implants in a
location outside the uterus and attempts to develop at that
site. The most common site of an ectopic pregnancy is the
fallopian tube, but it can occur in the ovary, the abdomen,
and the cervical wall. More than 95% of all ectopic pregnancies occur in the fallopian tube. (Illustration by Electronic
Illustrators Group.)

Medical
If the ectopic pregnancy is discovered in a very early
stage of development, the drug methotrexate may be
given. The best results are obtained when the pregnancy
is less than six weeks old and the tubal mass is no more
than 1.4 in (3.5 cm) in diameter. Methotrexate, which
has been used successfully since 1987, works by inhibiting the growth of rapidly growing cells. (It is also used to
treat some cancers.) Most side effects are mild and
temporary, but the patient must be monitored after
treatment. Usually the medication is injected into the
muscle in a single dose, but may also be given intravenously or injected directly into the fallopian tube to
dissolve the embryonic tissue. Methotrexate has also
been used to treat ovarian, abdominal, and cervical
pregnancies that are discovered in the early stages.
Surgical
When a laparoscopy is done to visualize the ectopic pregnancy, the scope can be fitted with surgical
tools and used to remove the ectopic mass immediately
after it is identified. The affected fallopian tube can be
repaired or removed as necessary. This procedure can
be done without requiring the patient to stay in the
hospital overnight.
When the pregnancy has ruptured, a surgical
incision into the abdomen, or laparotomy, is
1250

Human chorionic gonadotropin (hCG)—A hormone excreted during the development of an
embryo or fetus.
Laparoscopy—Examination of the contents of the
abdominal cavity with a fiberoptic tube inserted
through a small incision.
Laparotomy—Surgical incision into the abdomen
to locate, repair, and/or remove injured or diseased
tissues.
Pelvic inflammatory disease (PID)—Acute or
chronic inflammation in the pelvic cavity, particularly inflammation of the fallopian tubes (salpingitis) and its complications.
Rupture—A breaking apart of an organ or tissue.
Salpingitis—Inflammation of the fallopian tube.
Tubal pregnancy—Pregnancy in one of the fallopian tubes.
Zygote—The fertilized egg.

performed to stop the immediate loss of blood and
to remove the embryo. This usually requires general
anesthesia and a hospital stay. Every effort is made to
preserve and repair the injured fallopian tube.
However, if the fallopian tube has already ruptured,
repair is extremely difficult and the tube is usually
removed.

Alternative treatment
Ectopic pregnancy was first described in the eleventh century and was a potentially fatal condition
until the advent of surgery and blood transfusions in
the early twentieth century. The sophisticated diagnostic tools and surgical procedures developed since
the 1970s have equipped modern medicine with the
tools to not only save a woman’s life, but also to
preserve her future fertility.
Although there are herbal remedies for the temporary relief of the common symptoms of anxiety and
abdominal discomfort, prompt medical treatment is
the only sure remedy for ectopic pregnancy.
GALE ENCYCLOPEDIA OF MEDICINE

Description

Ectopic pregnancies are the leading cause of
pregnancy-related deaths in the first trimester and
account for 9% of all pregnancy-related deaths in
the United States. More than 1% of pregnancies are
ectopic, and they are becoming more common. The
reason for this increase is not clearly understood,
though it is thought that the dramatic increase in
sexually transmitted diseases (STD) is at least partly
responsible.
The earlier an ectopic pregnancy is diagnosed
and treated, the better the outcome. The chances of
having a successful pregnancy are lower after an
ectopic pregnancy, but depend on the extent of
permanent fallopian tube damage. If the tube has
been spared, chances are as high as 60%. The chances
of a successful pregnancy after the removal of one
tube are 40%.

Normally the body maintains a balance of fluid in
tissues by ensuring that the same of amount of water
entering the body also leaves it. The circulatory system
transports fluid within the body via its network of
blood vessels. The fluid, which contains oxygen and
nutrients needed by the cells, moves from the walls of
the blood vessels into the body’s tissues. After its nutrients are used up, fluid moves back into the blood vessels
and returns to the heart. The lymphatic system (a network of channels in the body that carry lymph, a colorless fluid containing white blood cells to fight infection)
also absorbs and transports this fluid. In edema, either
too much fluid moves from the blood vessels into the
tissues, or not enough fluid moves from the tissues back
into the blood vessels. This fluid imbalance can cause
mild to severe swelling in one or more parts of the body.

Causes and symptoms
Prevention
Many forms of ectopic pregnancy cannot be
prevented. However, tubal pregnancies, which make
up the majority of ectopic pregnancies, may be prevented by avoiding conditions that cause damage to
the fallopian tubes. Since half of all women who
experience ectopic pregnancy have a history of PID,
avoiding this infection or getting early diagnosis and
treatment for sexually transmitted diseases will
decrease the risk of a future problem.

Many ordinary factors can upset the balance of
fluid in the body to cause edema, including:


Immobility. The leg muscles normally contract and
compress blood vessels to promote blood flow with
walking or running. When these muscles are not used,
blood can collect in the veins, making it difficult for
fluid to move from tissues back into the vessels.



Heat. Warm temperatures cause the blood vessels to
expand, making it easier for fluid to cross into surrounding tissues. High humidity also aggravates this
situation.



Medications. Certain drugs, such as steroids, hormone replacements, nonsteroidal anti-inflammatory
drugs (NSAIDs), and some blood pressure medications may affect how fast fluid leaves blood vessels.



Intake of salty foods. The body needs a constant
concentration of salt in its tissues. When excess salt
is taken in, the body dilutes it by retaining fluid.



Menstruation and pregnancy. The changing levels of
hormones affect the rate at which fluid enters and
leaves the tissues.

Resources
ORGANIZATIONS

Resolve. 1310 Broadway, Somerville, MA 02144-1731. (617)
623-0744. <http://www.resolve.org>.

Karen Ericson, RN

Eczema see Dermatitis
ED see Impotence

Some medical conditions may also cause edema,
including:


I Edema
Definition
Edema is a condition of abnormally large fluid
volume in the circulatory system or in tissues between
the body’s cells (interstitial spaces).
GALE ENCYCLOPEDIA OF MEDICINE

Heart failure. When the heart is unable to maintain
adequate blood flow throughout the circulatory system, the excess fluid pressure within the blood vessels
can cause shifts into the interstitial spaces. Left-sided
heart failure can cause pulmonary edema, as fluid
shifts into the lungs. The patient may develop
rapid, shallow respirations, shortness of breath, and
a cough. Right-sided heart failure can cause pitting
1251

Edema

Prognosis

Edema

edema, a swelling in the tissue under the skin of the
lower legs and feet. Pressing this tissue with a finger
tip leads to a noticeable momentary indentation.


Kidney disease. The decrease in sodium and water
excretion can result in fluid retention and overload.



Thyroid or liver disease. These conditions can change
the concentration of protein in the blood, affecting
fluid movement in and out of the tissues. In advanced
liver disease, the liver is enlarged and fluid may buildup in the abdomen.



Malnutrition. Protein levels are decreased in the
blood, and in an effort to maintain a balance of
concentrations, fluid shifts out of the vessels and
causes edema in tissue spaces.

Some conditions that may cause swelling in just
one leg include:






Blood clots. Clots can cause pooling of fluid and may
be accompanied by discoloration and pain. In some
instances, clots may cause no pain.
Weakened veins. Varicose veins, or veins whose walls
or valves are weak, can allow blood to pool in the
legs. This is a common condition.
Infection and inflammation. Infection in leg tissues
can cause inflammation and increasing blood flow to
the area. Inflammatory diseases, such as gout or
arthritis, can also result in swelling.



Lymphedema. Blocked lymph channels may be
caused by infection, scar tissue, or hereditary conditions. Lymph that can’t drain properly results in
edema. Lymphedema may also occur after cancer
treatments, when the lymph system is impaired by
surgery, radiation, or chemotherapy.



Tumor. Abnormal masses can compress leg vessels
and lymph channels, affecting the rate of fluid
movement.

Symptoms vary depending on the cause of edema.
In general, weight gain, puffy eyelids, and swelling of
the legs may occur as a result of excess fluid volume.
Pulse rate and blood pressure may be elevated. Hand
and neck veins may be observed as fuller.

Diagnosis
Edema is a sign of an underlying problem, rather
than a disease unto itself. A diagnostic explanation
should be sought. Patient history and presenting
symptoms, along with laboratory blood studies, if
indicated, assist the health professional in determining
the cause of the edema.
1252

Treatment
Treatment of edema is based on the cause. Simple
steps to lessen fluid build-up may include:


Reducing sodium intake. A high sodium level causes
or aggravates fluid retention.



Maintaining proper weight. Being overweight slows
body fluid circulation and puts extra pressure on the
veins.



Exercise. Regular exercise stimulates circulation.



Elevation of the legs. Placing the legs at least 12 in
(30.5 cm) above the level of the heart for 10–15
minutes, three to four times a day, stimulates excess
fluid re-entry into the circulatory system.



Use of support stocking. Elastic stockings, available
at most medical supply or drug stores, will compress
the leg vessels, promoting circulation and decreasing
pooling of fluid due to gravity.



Massage. Massaging the body part can help to stimulate the release of excess fluids, but should be
avoided if the patient has blood clots in the veins.



Travel breaks. Sitting for long periods will increase
swelling in the feet and ankles. Standing and/or
walking at least every hour or two will help stimulate
blood flow.

The three ‘‘Ds’’–diuretics, digitalis, and diet–are
frequently prescribed for medical conditions that
result in excess fluid volume. Diuretics are medications
that promote urination of sodium and water. Digoxin
is a digitalis preparation that is sometimes needed to
decrease heart rate and increase the strength of the
heart’s contractions. Dietary recommendations
include less sodium in order to decrease fluid retention. Consideration of adequate protein intake is
also made.
For patients with lymphedema, a combination of
therapies may prove effective. Combined decongestive
therapy includes the use of manual lymph drainage
(MLD), compression bandaging, garments and
pumps, and physical therapy. MLD involves the use
of light massage of the subcutaneous tissue where the
lymph vessels predominate. Massage begins in an area
of the body trunk where there is normal lymph function and proceeds to areas of lymphatic insufficiency,
in an effort to stimulate new drainage tract development. (MLD should not be used for patients with
active cancer, deep vein clots, congestive heart failure,
or cellulitis.) MLD sessions are followed by application of compression garments or pumps. Physical
therapy is aimed at strengthening the affected limb
and increasing joint mobility.
GALE ENCYCLOPEDIA OF MEDICINE

Edema
Gross lymphedema in the arm of an elderly woman following radiotherapy treatment for breast cancer. (Photograph by
Dr. P. Marazzi. Photo Researchers, Inc. Reproduced by permission.)

KEY TERMS
Digitalis—A naturally occuring compound used in
the preparation of the medication, digoxin, prescribed to increase the heart rate and strengthen
the force of the heart’s contractions.
Diuretics—Medications used in the treatment of
fluid overload, to promote excretion of sodium
and water.
Interstitial spaces—Areas of the body occuring
outside the vessels or organs, between the cells.
Pitting edema—A swelling in the tissue under
the skin, resulting from fluid accumulation, that is
measured by the depth of indentation made by
finger pressure over a boney prominence.

Alternative treatment
Dietary changes, in addition to cutting back the
amount of sodium eaten, may also help reduce
GALE ENCYCLOPEDIA OF MEDICINE

edema. Foods that worsen edema, such as alcohol,
caffeine, sugar, dairy products, soy sauce, animal
protein, chocolate, olives, and pickles, should be
avoided. Diuretic herbs can also help relieve edema.
One of the best herbs for this purpose is dandelion
(Taraxacum mongolicum), since, in addition to its
diuretic action, it is a rich source of potassium.
(Diuretics flush potassium from the body and it
must be replaced to avoid potassium deficiency.)
Hydrotherapy using daily contrast applications of
hot and cold (either compresses or immersion) may
also be helpful.
Resources
ORGANIZATIONS

Lymphedema and Wound Care Clinic of Austin. 5750
Balcones Dr., Ste. 110, Austin, TX 78731. (512)
453-1930.

Kathleen D. Wright, RN

Edrophonium test see Tensilon test
1253

Edwards’ syndrome

I Edwards’ syndrome
Definition
Edwards’ syndrome is caused by an extra copy of
chromosome 18. For this reason, it is also called
trisomy 18 syndrome. The extra chromosome is lethal
for most babies born with this condition. It causes
major physical abnormalities and severe mental
retardation, and very few children afflicted with this
disease survive beyond a year.

Description
Humans normally have 23 pairs of chromosomes.
Chromosomes are numbered 1–22, and the 23rd pair is
composed of the sex chromosomes, X and Y. A person
inherits one set of 23 chromosomes from each parent.
Occasionally, a genetic error occurs during egg or
sperm cell formation. A child conceived with such an
egg or sperm cell may inherit an incorrect number of
chromosomes.
In the case of Edwards’ syndrome, the child inherits three, rather than two, copies of chromosome 18.
Trisomy 18 occurs in approximately one in every 3,000
newborns and affects girls more often than boys.
Women older than their early thirties have a greater
risk of conceiving a child with trisomy 18, but it can
occur in younger women.

Causes and symptoms
A third copy of chromosome 18 causes numerous
abnormalities. Most children born with Edwards’ syndrome appear weak and fragile, and they are often
underweight. The head is unusually small and the
back of the head is prominent. The ears are malformed
and low-set, and the mouth and jaw are small. The
baby may also have a cleft lip or cleft palate.
Frequently, the hands are clenched into fists, and the
index finger overlaps the other fingers. The child may
have clubfeet and toes may be webbed or fused.
Numerous problems involving the internal organs
may be present. Abnormalities often occur in the lungs
and diaphragm (the muscle that controls breathing),
and heart defects and blood vessel malformations are
common. The child may also have malformed kidneys
and abnormalities of the urogenital system.

Diagnosis
Physical abnormalities point to Edwards’ syndrome, but definitive diagnosis relies on karyotyping.
1254

KEY TERMS
Aminocentesis—A procedure in which a needle is
inserted through a pregnant woman’s abdomen
and into her uterus to withdraw a small sample of
amniotic fluid. The amniotic fluid can be examined
for signs of disease or other problems afflicting
the fetus.
Chorionic villus sampling—A medical test that is
best done during weeks 10–12 of a pregnancy. The
procedure involves inserting a needle into the
placenta and withdrawing a small amount of the
chorionic membrane for analysis.
Chromosome—A structure composed of deoxyribonucleic acid (DNA) contained within a cell’s
nucleus (center) where genetic information is
stored. Human have 23 pairs of chromosomes,
each of which has recognizable characteristics
(such as length and staining patterns) that allow
individual chromosomes to be identified.
Identification is assigned by number (1–22) or letter
(X or Y).
Karyotyping—A laboratory test used to study an
individual’s chromosome make-up. Chromosomes
are separated from cells, stained, and arranged
in order from largest to smallest so that their
number and structure can be studied under a
microscope.
Maternal serum analyte screening—A medical
procedure in which a pregnant woman’s blood is
drawn and analyzed for the levels of certain hormones and proteins. These levels can indicate
whether there may be an abnormality in the unborn
child. This test is not a definitive indicator of a
problem and is followed by more specific testing
such as amniocentesis or chorionic villus sampling.
Trisomy—A condition in which a third copy of a
chromosome is inherited. Normally only two
copies should be inherited.
Ultrasound—A medical test that is also called
ultrasonography. Sound waves are directed against
internal structures in the body. As sound waves
bounce off the internal structure, they create an
image on a video screen. An ultrasound of a fetus
at weeks 16–20 of a pregnancy can be used to
determine structural abnormalities.

Karyotyping involves drawing the baby’s blood or
bone marrow for a microscopic examination of the
chromosomes. Using special stains and microscopy,
GALE ENCYCLOPEDIA OF MEDICINE

Trisomy 18 can be detected before birth. If a
pregnant woman is older than 35, has a family history
of genetic abnormalities, has previously conceived a
child with a genetic abnormality, or has suffered
earlier miscarriages, she may undergo tests to determine whether her child carries genetic abnormalities.
Potential tests include maternal serum analysis or
screening, ultrasonography, amniocentesis, and
chorionic villus sampling.

I Ehlers-Danlos syndrome
Definition
The Ehlers-Danlos syndromes (EDS) refer to a
group of inherited disorders that affect collagen structure and function. Genetic abnormalities in the
manufacturing of collagen within the body affect
connective tissues, causing them to be abnormally
weak.

Description

Treatment
There is no cure for Edwards’ syndrome. Since
trisomy 18 babies frequently have major physical
abnormalities, doctors and parents face difficult
choices regarding treatment. Abnormalities can be
treated to a certain degree with surgery, but extreme
invasive procedures may not be in the best interests of
an infant whose lifespan is measured in days or weeks.
Medical therapy often consists of supportive care with
the goal of making the infant comfortable, rather than
prolonging life.

Prognosis
Most children born with trisomy 18 die within
their first year of life. The average lifespan is less than
two months for 50% of the children, and 90–95% die
before their first birthday. The 5–10% of children who
survive their first year are severely mentally retarded.
They need support to walk, and learning is limited.
Verbal communication is also limited, but they can
learn to recognize and interact with others.

Prevention
Edwards’ syndrome cannot be prevented.
Resources

Collagen is a strong, fibrous protein that lends
strength and elasticity to connective tissues such as
the skin, tendons, organ walls, cartilage, and blood
vessels. Each of these connective tissues requires collagen tailored to meet its specific purposes. The many
roles of collagen are reflected in the number of genes
dedicated to its production. There are at least 28 genes
in humans that encode at least 19 different types of
collagen. Mutations in these genes can affect basic
construction as well as the fine-tuned processing of
the collagen.
EDS was originally described by Dr. Van
Meekeren in 1682. Dr. Ehlers and Dr. Danlos further
characterized the disease in 1901 and 1908, respectively. Today, according to the Ehlers-Danlos
National Foundation, one in 5,000 to one in 10,000
people are affected by some form of EDS.
EDS is a group of genetic disorders that usually
affects the skin, ligaments, joints, and blood vessels.
Classification of EDS types was revised in 1997. The
new classification involves categorizing the different
forms of EDS into six major sub-types, including classical, hypermobility, vascular, kyphoscoliosis, arthrochalasia, and dermatosparaxis, and a collection of rare
or poorly defined varieties. This new classification is
simpler and based more on descriptions of the actual
symptoms.

ORGANIZATIONS

Chromosome 18 Registry & Research Society. 6302 Fox
Head, San Antonio, TX 78247. (210) 657-4968.
<http://www.chromosome18.org>.
Support Organization for Trisomy 18, 13, and Related
Disorders (SOFT). 2982 South Union St., Rochester,
NY 14624. (800) 716-7638. <http://
www.trisomy.org>.

Classical type

Egyptian conjunctivitis see Trachoma

Under the old classification system, EDS classical
type was divided into two separate types: type I and
type II. The major symptoms involved in EDS classical
type are the skin and joints. The skin has a smooth,
velvety texture and bruises easily. Affected individuals
typically have extensive scaring, particularly at the
knees, elbows, forehead, and chin. The joints are hyperextensible, giving a tendency towards dislocation of the
hip, shoulder, elbow, knee, or clavicle. Due to
decreased muscle tone, affected infants may experience

GALE ENCYCLOPEDIA OF MEDICINE

1255

Julia Barrett

EEG see Electroencephalography

Ehlers-Danlos syndrome

individual chromosomes are identified, and the
presence of an extra chromosome 18 is revealed.

Ehlers-Danlos syndrome

a delay in reaching motor milestones. Children may
have a tendency to develop hernias or other organ
shifts within the abdomen. Sprains and partial or complete joint dilocations are also common. Symptoms can
range from mild to severe. EDS classical type is inherited in an autosomal dominant manner.
There are three major clinical diagnostic criteria
for EDS classical type. These include skin hyperextensibility, unusually wide scars, and joint hypermobility.
At this time there is no definitive test for the diagnosis
of classical EDS. Both DNA and biochemical studies
have been used to help identify affected individuals. In
some cases, a skin biopsy has been found to be useful
in confirming a diagnosis. Unfortunately, these tests
are not sensitive enough to identify all individuals with
classical EDS. If there are multiple affected individuals in a family, it may be possible to perform prenatal diagnosis using a DNA information technique
known as a linkage study.
Hypermobility type
Excessively loose joints are the hallmark of this
EDS type, formerly known as EDS type III. Both large
joints, such as the elbows and knees, and small joints,
such as toes and fingers, are affected. Partial and total
joint dislocations are common, and particularly
involve the jaw, knee, and shoulder. Many individuals
experience chronic limb and joint pain, although x rays
of these joints appear normal. The skin may also
bruise easily. Osteoarthritis is a common occurrence
in adults. EDS hypermobility type is inherited in an
autosomal dominant manner.
There are two major clinical diagnostic criteria for
EDS hypermobility type. These include skin involvement (either hyperextensible skin or smooth and velvety skin) and generalized joint hypermobility. At this
time there is no test for this form of EDS.
Vascular type
Formerly called EDS type IV, EDS vascular type
is the most severe form. The connective tissue in the
intestines, arteries, uterus, and other hollow organs
may be unusually weak, leading to organ or blood
vessel rupture. Such ruptures are most likely between
ages 20 and 40, although they can occur any time, and
may be life-threatening.
There is a classic facial appearance associated
with EDS vascular type. Affected individuals tend to
have large eyes, a thin pinched nose, thin lips, and a
slim body. The skin is thin and translucent, with veins
dramatically visible, particularly across the chest.
1256

The large joints have normal stability, but small
joints in the hands and feet are loose, showing hyperextensibility. The skin bruises easily. Other complications may include collapsed lungs, premature aging of
the skin on the hands and feet, and ruptured arteries
and veins. After surgery there tends to be poor wound
healing, a complication that tends to be frequent and
severe. Pregnancy also carries the risk complications.
During and after pregnancy there is an increased risk
of the uterus rupturing and of arterial bleeding. Due to
the severe complications associated with EDS type IV,
death usually occurs before the fifth decade. A study of
419 individuals with EDS vascular type, completed in
2000, found that the median survival rate was 48 years,
with a range of six to 73 years. EDS vascular type is
inherited in an autosomal dominant manner.
There are four major clinical diagnostic criteria
for EDS vascular type. These include thin translucent skin, arterial/intestinal/uterine fragility or rupture, extensive bruising, and characteristic facial
appearance. EDS vascular type is caused by a change
in the gene COL3A1, which codes for one of the
collagen chains used to build Collage type III.
Laboratory testing is available for this form of
EDS. A skin biopsy may be used to demonstrate the
structurally abnormal collagen. This type of biochemical test identifies more than 95% of individuals
with EDS vascular type. Laboratory testing is recommended for individuals with two or more of the
major criteria.
DNA analysis may als be used to identify the
change within the COL3A1 gene. This information
may be helpful for genetic counseling purposes.
Prenatal testing is available for pregnancies in which
an affected parent has been identified and their DNA
mutation is known or their biochemical defect has
been demonstrated.
Kyphoscoliosis type
The major symptoms of kyphoscoliosis type, formerly called EDS type VI, are general joint looseness.
At birth, the muscle tone is poor, and motor skill
development is subsequently delayed. Also, infants
with this type of EDS have an abnormal curvature of
the spine (scoliosis). The scoliosis becomes progressively worse with age, with affected individuals
usually unable to walk by age 20. The eyes and skin
are fragile and easily damaged, and blood vessel
involvement is a possibility. The bones may also be
affected as demonstrated by a decrease in bone mass.
Kyphoscoliosis type is inherited in an autosomal
recessive manner.
GALE ENCYCLOPEDIA OF MEDICINE

Prenatal testing is available if a pregnancy is
known to be at risk and an identified affected family
member has had positive laboratory testing. An
amniocentesis may be performed in which fetal cells
are removed from the amniotic fluid and enzyme
activity is measured.
Arthrochalasia type
Dislocation of the hip joint typically accompanies
arthrochalasia type EDS, formerly called EDS type
VIIB. Other joints are also unusually loose, leading
to recurrent partial and total dislocations. The skin
has a high degree of stretchability and bruises easily.
Individuals with this type of EDS may also experience
mildly diminished bone mass, scoliosis, and poor
muscle tone. Arthrochalasia type is inherited in an
autosomal dominant manner.
There are two major clinical diagnostic criteria
for EDS arthrochalasia type. These include sever
generalized joing hypermobility and bilateral hip
dislocation present at birth. This form of EDS is
caused by a change in either of two components of
Collage type I, called proa1(I) type A and proa2(I)
type B. A skin biopsy may be preformed to demonstrate an abnormality in either components. Direct
DNA testing is also available.
Dermatosparaxis type

Ehlers-Danlos syndrome

There are four major clinical diagnostic criteria
for EDS kyphoscoliosis type. These include generaly
loose joints, low muscle tone at birth, scoliosis at birth
(which worsens with age), and a fragility of the eyes,
which may give the white area of the eye a blue tint or
cause the eye to rupture. This form of EDS is caused
by a change in the PLOD gene on chromosome 1,
which encodes the enzyme lysyl hydroxylase. A
laboratory test is available in which urinary hydroxylysyl pryridinoline is measured. This test, performed
on urine is extremely senstive and specific for EDS
kyphoscolios type. Laboratory testing is recommended for infants with three or more of the major
diagnostic criteria.

Elasticity of the skin is one characteristic of this rare
disorder. (Photograph by Biophoto Associates, Photo
Researchers, Inc. Reproduced by permission.)

form of EDS is caused by a change in the enzyme
called procollagen I N-terminal peptidase. A skin
biopsy may be preformed for a definitive diagnosis of
Dermatosparaxis type.
Other types
There are several other forms of EDS that have
not been as clearly defined as the aforementioned
types. Forms of EDS within this category may present
with soft, mildly stretchable skin, shortened bones,
chronic diarrhea, joint hypermobility and dislocation,
bladder rupture, or poor wound healing. Inheritance
patterns within this group include X-linked recessive,
autosomal dominant, and autosomal recessive.

Causes and symptoms
There are numerous types of EDS, all caused by
changes in one of several genes. The manner in which
EDS is inherited depends on the specific gene
involved. There are three patterns of inheritance for
EDS: autosomal dominant, autosomal recessive, and
X-linked (extremely rare).

Individuals with this type of EDS, once called type
VIIC, have extremely fragile skin that bruises easily
but does not scar excessively. The skin is soft and may
sag, leading to an aged appearance even in young
adults. Individuals may also experience hernias.
Dermatosparaxis type is inherited in an autosomal
recessive manner.

Chromosomes are made up of hundreds of small
units known as genes, which contain the genetic
material necessary for an individual to develop and
function. Humans have 46 chromosomes, which are
matched into 23 pairs. Because chromosomes are
inherited in pairs, each individual receives two
copies of each chromosome and likewise two copies
of each gene.

There are two major clinical diagnostic criteria for
EDS dematosparaxis type. These include severe skin
fragility and sagging or aged appearing skin. This

Changes or mutations in genes can cause
genetic diseases in several different ways, many of
which are represented within the spectrum of EDS.

GALE ENCYCLOPEDIA OF MEDICINE

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Ehlers-Danlos syndrome

In autosomal dominant EDS, only one copy of a
specific gene must be changed for a person to have
EDS. In autosomal recessive EDS, both copies of a
specific gene must be changed for a person to have
EDS. If only one copy of an autosomal recessive
EDS gene is changed the person is referred to as a
carrier, meaning they do not have any of the signs
or symptoms of the disease itself, but carry the
possibility of passing on the disorder to a future
child. In X-linked EDS a specific gene on the X
chromosome must be changed. However, this
affects males and females differently because
males and females have a different number of X
chromosomes.
The few X-linked forms of EDS fall under the
category of X-linked recessive. As with autosomal
recessive, this implies that both copies of a specific gene
must be changed for a person to be affected. However,
because males only have one X-chromosome, they
are affected if an X-linked recessive EDS gene is
changed on their single X-chromosome. That is, they
are affected even though they have only one changed
copy. On the other hand, that same gene must be
changed on both of the X-chromosomes in a female
for her to be affected.
Although there is much information regarding the
changes in genes that cause EDS and their various
inheritance patterns, the exact gene mutation for all
types of EDS is not known.

Diagnosis
Clinical symptoms such as extreme joint looseness
and unusual skin qualities, along with family history,
can lead to a diagnosis of EDS. Specific tests, such as
skin biopsies are available for diagnosis of certain
types of EDS, including vascular, arthrochalasia, and
dermatosparaxis types. A skin biopsy involves removing a small sample of skin and examining its microscopic structure. A urine test is available for the
Kyphoscoliosis type.
Management of all types of EDS may include
genetic counseling to help the affected individual and
their family understand the disorder and its impact on
other family members and future children.
If a couple has had a child diagnosed with EDS
the chance that they will have another child with the
same disorder depends on with what form of EDS the
child has been diagnosed and if either parent is
affected by the same disease or not.
Individuals diagnosed with an autosomal dominant form of EDS have a 50% chance of passing the
1258

same disorder on to a child in each pregnancy.
Individuals diagnosed with an autosomal recessive
form of EDS have an extremely low risk of having a
child with the same disorder.
X-linked recessive EDS is accompanied by a
slightly more complicated pattern of inheritance. If
a father with an X-linked recessive form of EDS
passes a copy of his X chromosome to his children,
the sons will be unaffected and the daughters will be
carriers. If a mother is a carrier for an X-linked
recessive form of EDS, she may have affected or
unaffected sons, or carrier or unaffected daughters,
depending on the second sex chromosome inherited
from the father.
Prenatal diagnosis is available for specific forms
of EDS, including kyphosocliosis type and vascular
type. However, prenatal testing is only a possibility in
these types if the underlying defect has been found in
another family member.

Treatment
Medical therapy relies on managing symptoms
and trying to prevent further complications. There is
no cure for EDS.
Braces may be prescribed to stabilize joints,
although surgery is sometimes necessary to repair joint
damage caused by repeated dislocations. Physical
therapy teaches individuals how to strengthen
muscles around joints and may help to prevent or
limit damage. Elective surgery is discouraged due to
the high possibility of complications.
Alternative treatment
There are anecdotal reports that large daily doses
0.04–0.14 oz (1–4 g) of vitamin C may help decrease
bruising and aid in wound healing. Constitutional
homeopathic treatment may be helpful in maintaining optimal health in persons with a diagnosis of
EDS. An individual with EDS should discuss these
types of therapies with their doctor before beginning
them on their own. Therapy that does not require
medical consultation involves protecting the skin
with sunscreen and avoiding activities that place
stress on the joints.

Prognosis
The outlook for individuals with EDS depends
on the type of EDS with which they have been
diagnosed. Symptoms vary in severity, even within
one sub-type, and the frequency of complications
GALE ENCYCLOPEDIA OF MEDICINE

Arthrochalasia—Excessive loosness of the joints.
Blood vessels—General term for arteries, veins, and
capillaries that transport blood throughout the body.
Cartilage—Supportive connective tissue that cushions bone at the joints or which connects muscle to
bone.
Collagen—The main supportive protein of cartilage, connective tissue, tendon, skin, and bone.
Connective tissue—A group of tissues responsible for
support throughout the body; includes cartilage, bone,
fat, tissue underlying skin, and tissues that support
organs, blood vessels, and nerves throughout the body.
Dermatosparaxis—Skin fragility caused by abnormal collagen.
Hernia—A rupture in the wall of a body cavity,
through which an organ may protrude.
Homeopathic—A holistic and natural approach to
healthcare.
Hyperextensibility—The ability to extend a joint
beyond the normal range.
Hypermobility—Unusual flexibility of the joints,
allowing them to be bent or moved beyond their
normal range of motion.
Joint dislocation—The displacement of a bone.
Kyphoscoliosis—Abnormal front-to-back and sideto-side curvature of the spine.
Ligament—A type of connective tissue that connects bones or cartilage and provides support and
strength to joints.
Osteoarthritis—A degenerative joint disease that
causes pain and stiffness.
Scoliosis—An abnormal, side-to-side curvature of
the spine.
Tendon—A strong connective tissue that connects
muscle to bone.
Uterus—A muscular, hollow organ of the female
reproductive tract. The uterus contains and
nourishes the embryo and fetus from the time the
fertilized egg is implanted until birth.
Vascular—Having to do with blood vessels.

changes on an individual basis. Some individuals
have negligible symptoms while others are severely
restricted in their daily life. Extreme joint instability
and scoliosis may limit a person’s mobility. Most
GALE ENCYCLOPEDIA OF MEDICINE

individuals will have a normal lifespan. However,
those with blood vessel involvement, particularly
those with EDS vascular type, have an increased
risk of fatal complications.
EDS is a lifelong condition. Affected individuals
may face social obstacles related to their disease on a
daily basis. Some people with EDS have reported living with fears of significant and painful skin ruptures,
becoming pregnant (especially those with EDS vascular type), their condition worsening, becoming unemployed due to physical and emotional burdens, and
social stigmatization in general.
Constant bruises, skin wounds, and trips to the
hospital take their toll on both affected children and
their parents. Prior to diagnosis parents of children
with EDS have found themselves under suspicion of
child abuse.
Some people with EDS are not diagnosed until
well into adulthood and, in the case of EDS vascular
type, occasionally not until after death due to complications of the disorder. Not only may the diagnosis
itself be devastating to the family, but in many cases
other family members find out for the first time they
are at risk for being affected.
Although individuals with EDS face significant
challenges, it is important to remember that each
person is unique with their own distinguished
qualities and potential. Persons with EDS go on to
have families, to have careers, and to be accomplished citizens, surmounting the challenges of their
disease.
Resources
PERIODICALS

‘‘Clinical and Genetic Features of Ehlers-DanlosSyndrome
Type IV, the Vascular Type.’’ The New England Journal
ofMedicine 342, no. 10 (2000).
‘‘Living a Restricted Life with Ehlers-DanlosSyndrome.’’
International Journal of Nursing Studies 37 (2000):
111–118.
ORGANIZATIONS

Ehlers-Danlos Support Group - UK. PO Box 335, Farnham,
Surrey, GU10 1XJ. UK 01252 690 940. <http://
www.atv.ndirect.co.uk>.
Elhers-Danlos National Foundation. 6399 Wilshire
Blvd., Ste 203, Los Angeles, CA 90048 (323)
651-3038. Fax: (323) 651-1366. <http://
www.ednf.org>.
OTHER

GeneClinics. <http://www.geneclinics.org>.

Java O. Solis, MS
1259

Ehlers-Danlos syndrome

KEY TERMS

Ehrlichiosis

I Ehrlichiosis
Definition
Ehrlichiosis is a bacterial infection that is spread
by ticks. Symptoms include fever, chills, headache,
muscle aches, and tiredness.

Description
Ehrlichiosis is a tick-borne disease caused by
infection with Ehrlichia bacteria. Ticks are small,
blood-sucking arachnids. Although some ticks carry
disease-causing organisms, most do not. When an
animal or person is bitten by a tick that carries
bacteria, the bacteria are passed to that person or
animal during the tick’s feeding process. It is believed
that the tick must remain attached to the person
or animal for at least 24 hours to spread the infection.
There are two forms of ehrlichiosis in the United
States; human monocytic ehrlichiosis and human
granulocytic ehrlichiosis. Monocytic ehrlichiosis is
caused by Ehrlichia chaffeensis, which is spread by
the Lone Star tick, Amblyomma americanum. As of
early 1998, about 400 cases of monocytic ehrlichiosis
had been reported in 30 states, primarily in the southeastern and south central United States. The bacteria
that causes granulocytic ehrlichiosis is not known, but
suspected to be either Ehrlichia equi or Ehrlichia
phagocytophila. Granulocytic ehrlichiosis is probably
spread by the blacklegged tick Ixodes scapularis
(which also spreads Lyme disease). About 100 cases
of granulocytic ehrlichiosis have been reported
in Connecticut, Massachusetts, Rhode Island,
Minnesota, New York, and Wisconsin.

Causes and symptoms
Both forms of ehrlichiosis have similar symptoms,
and the illnesses can range from mild to severe and
life-threatening. Risk factors include old age and
exposure to ticks through work or recreation.
Symptoms occur seven to 21 days following a tick
bite although patients may not recall being bitten.
Fever, tiredness, headache, muscle aches, chills, loss
of appetite, confusion, nausea, and vomiting are
common to both diseases. A rash may occur.

Diagnosis
Ehrlichiosis may be diagnosed and treated by
doctors who specialize in blood diseases (hematologists) or an infectious disease specialist. Because
ehrlichiosis is not very common and the symptoms are
1260

KEY TERMS
Tick-borne disease—A disease that is spread to
animals by the bite of an infected tick.

not unique, it may be misdiagnosed. A recent history of
a tick bite is helpful in the diagnosis. Blood tests will be
done to look for antibodies to Ehrlichia. Staining and
microscopic examination of the blood sample may
show Ehrlichia bacteria inside white blood cells.
Another test, called polymerase chain reaction (PCR),
is a very sensitive assay to detect bacteria in the blood
sample, but it is not always available.

Treatment
Antibiotic treatment should begin immediately if
ehrlichiosis is suspected, even if laboratory results are
not available. Treatment with either tetracycline
(Sumycin, Achromycin V) or doxycycline (Monodox,
Vibramycin) is recommended. Many patients with
ehrlichiosis are admitted to the hospital for treatment.

Prognosis
For otherwise healthy people, a full recovery is
expected following treatment for ehrlichiosis. Elderly
patients are at a higher risk for severe disease, which
may be fatal. Serious complications include lung or
gastrointestinal bleeding. Two to 10 patients out of
100 die from the disease.

Prevention
The only prevention for ehrlichiosis is to minimize
exposure to ticks by staying on the trail when walking
through the woods, avoiding tall grasses, wearing long
sleeves and tucking pant legs into socks, wearing insect
repellent, and checking for ticks after an outing.
Remove a tick as soon as possible by grasping the
tick with tweezers and gently pulling.
Resources
BOOKS

McDade, Joseph E., and James G. Olsen. ‘‘Ehrlichiosis,
Q Fever,Typhus, Rickettsialpox, and Other
Rickettsioses.’’ In Infectious Diseases. 2nd ed.
Philadelphia: W. B. Saunders Co., 1998.

Belinda Rowland, PhD

EKG see Electrocardiography
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Elder abuse is a general term used to describe
harmful acts toward an elderly adult, such as physical
abuse, sexual abuse, emotional or psychological
abuse, financial exploitation, and neglect, including
self-neglect.

Description
Results from the National Elder Abuse Incidence
Study, funded in part by the Administration on Aging,
suggest that over 500,000 people 60 years of age and
older are abused or neglected each year in the United
States. It was also found that four times as many
incidents of abuse, neglect, or self-neglect are never
reported, causing researchers to estimate that as
many as two million elderly persons in the United
States are abused each year. In 90% of the cases, the
abusers were found to be family members and most
often were the adult children or spouses of those
abused. In addition, equal numbers of men and
women have been identified as the abusers. However,
women, especially those over 80 years of age, tend to
be victimized more than men.
Elder abuse can take place anywhere, but the two
main settings addressed by law are domestic settings,
such as the elder’s home or the caregiver’s home, and
institutional settings, such as a nursing home or
group home. In general, there are five basic types of
elderly abuse: physical, sexual, emotional or psychological, financial, and neglect. Data from National
Center on Elder Abuse indicates that more than half
of the cases reported involve some kind of neglect,
whereas 1 in 7 cases involve physical abuse. It is
considered neglect when a caretaker deprives an
elderly person of the necessary care needed in order
to avoid physical or mental harm. Sometimes the
behavior of an elderly person threatens his or her
own health; in those cases, the abuse is called selfneglect. Physical abuse refers to physical force that
causes bodily harm to an elderly person, such as
slapping, pushing, kicking, pinching, or burning.
About 1 in 8 cases of elderly abuse involve some
form of financial exploitation, which is defined as the
use of an elderly person’s resources without his or her
consent. The National Center on Elder Abuse defines
emotional and psychological abuse of a senior as
causing anguish, pain, or distress through verbal or
nonverbal acts, such as verbal assaults, insults, intimidation, and humiliation, for example. Isolating elderly
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Elder abuse is a complex problem that can be
caused by many factors. According to the National
Center on Elder Abuse, social isolation and mental
impairment are two factors of elder abuse. Studies
show that people advanced in years, such as in their
eighties, with a high level of frailty and dependency
are more likely to be victims of elder abuse than people
who are younger and better equipped to stand up
for themselves. Because spouses make up a large
percentage of elder abusers, at least 40% statistically,
some research has been done in the area, which shows
that a pattern of domestic violence is associated with
many of the cases. The risk of elder abuse appears
to be especially high when adult children live with
their elderly parents for financial reasons or because
they have personal problems, such as drug dependency or mental illness. Some experts have speculated
that elderly people living in rural areas with their
caretakers may have a higher risk of being abused
than city dwellers. The idea behind this theory is
that the opportunity exists for the abuse to occur,
but there is less likelihood that the abuser will be
caught. More research in this very important area is
needed in order to illuminate the relationship
between these factors.
The National Center on Elder Abuse identifies the
following as signs of elder abuse:


Bruises, pressure marks, broken bones, abrasions,
and burns may indicate physical abuse or neglect.



Unexplained withdrawal from normal activities and
unusual depression may be indicators of emotional
abuse.



Bruises around the breasts or genital area, as well as
unexplained bleeding around the genital area, may
be signs of sexual abuse.



Large withdrawals of money from an elder’s bank
account, sudden changes in a will, and the sudden
disappearance of valuable items may be indications
of financial exploitation.



Bedsores, poor hygiene, unsanitary living conditions, and unattended medical needs may be signs
of neglect.
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Elder Abuse

I Elder Abuse

persons from their friends and family as well as
giving them the silent treatment are two other forms
of emotional and psychological abuse. Any kind of
non-consensual sexual contact with an elderly person
that takes place without his or her consent is considered sexual abuse.

Elder Abuse



Failure to take necessary medicines, leaving a
burning stove unattended, poor hygiene, confusion,
unexplained weight loss, and dehydration may all be
signs of self-neglect.

Diagnosis and Treatment
The National Committee for the Prevention of
Elder Abuse notes that Adult Protective Services
(APS) caseworkers are often on the front lines when
it comes to elderly abuse. People being abused or those
who believe abuse is taking place can turn to their local
APS office for help. The APS routinely screens calls,
keeps all information confidential, and, if necessary,
sends a caseworker out to conduct an investigation.
In the event that a crisis intervention is needed, the
APS caseworker can arrange for any necessary emergency treatment. If it is unclear whether elder abuse
has taken place, the APS caseworker can serve as a
liaison between the elderly person and other community agencies.
According to the National Committee for the
Prevention of Elder Abuse, ‘‘professionals in the field
of aging are often the first to discover signs of elder
abuse.’’ Providing encouragement and advice, they
play a critical role in educating others with regard
to the needs of the elderly. They not only provide
valuable support to the victims of abuse, but they
also monitor high-risk situations and gather important information that can help validate that abuse has
taken place.
Some people might think that a person who
has cognitive impairment might be unable to describe
mistreatment; however, that is not the case. In fact,
guidelines set by the American Medical Association
call for ‘‘routine questions about abuse and neglect
even among patients with cognitive impairment
in order to improve the identification of cases and
implement appropriate treatment and referral.’’
Rather than an inability to describe mistreatment,
what might stop an elderly person from reporting
abuse is a sense of embarrassment or fear of retaliation. To complicate matters, differences exist among
cultural groups regarding what defines abuse.
Therefore, most states have established laws that
define elder abuse and require health care providers to
report any cases they encounter with penalties
attached for failing to do so. Indeed, statistics show
that health care providers, for example, report almost
25% of the known cases of elder abuse. Therefore,
physicians play a very important role in identifying
and treating elders who have been abused. And yet, in
an article published by the Journal of the American
1262

Geriatrics Society, Dr. Conlin pointed out that only
1 of every 13 cases of elder abuse are reported by
physicians. There may be several reasons for this. In
some cases, the problem may simply go unnoticed,
especially if the physician has no obvious reason to
suspect any wrongdoing. In other cases, the patient
may hide or deny the problem.
In recent years, much media attention has been
focused on elderly abuse that takes place in institutional settings. Anyone who believes that a loved one
is being abused while in a nursing home or other
institutional setting should contact the authorities for
assistance immediately.

Prognosis
The mortality rate of an elderly person who has
been mistreated is higher than the mortality rate
of an elderly person who has not experienced abuse.
Nonetheless, numerous success stories exist regarding successful interventions. Social workers and
health care professionals, as well as concerned citizens from a variety of backgrounds, have played a
key role in identifying and obtaining treatment for
abused elders.

Prevention
Planning for the future is one of the best ways to
avoid elder abuse. Consider a variety of retirement
options, ones that will encourage safety as well as
independence. It is important to stay active in the
community. Avoiding isolation minimizes the likelihood that abuse will occur. Seek professional
counsel when necessary; it is important for everyone
to know their rights and to be advocates on their
own behalf.
Resources
PERIODICALS

Clarke, M. E., Pierson, W. ‘‘Management of elder abuse in
the emergency department.’’ Emergency Medical
Clinics of North America 17 (1999): 631–644.
Conlin, M. ‘‘Silent suffering: a case study of elder abuse and
neglect.’’ Journal of the American Geriatrics Society 43
(1995): 1303–1308.
Lachs, M. S., Willimas, C. S., O’Brien, S., Pillemer, K. A.,
Charlson, M. E. ‘‘The mortality of elderly mistreatment.’’ Journal of the American Medical Association 280
(1998): 429–432.
OTHER

Administration on Aging ‘‘Elder Rights & Resources.
Elder Abuse.’’ Administration on Aging 10 December
2004 Administration on Aging, Department of
GALE ENCYCLOPEDIA OF MEDICINE

Lee Ann Paradise

I Electric shock injuries
Definition
Electric shock injuries are caused by lightning or
electric current from a mechanical source passing
through the body.

Description
Electric shocks are responsible for about 1,000
deaths in the United States each year, or about 1%
of all accidental deaths.

Causes and symptoms
The severity of injury depends on the current’s
pressure (voltage), the amount of current (amperage), the type of current (direct vs. alternating), the
body’s resistance to the current, the current’s path
through the body, and how long the body remains
in contact with the current. The interplay of these
factors can produce effects ranging from barely
noticeable tingling to instant death; every part of the
body is vulnerable. Although the severity of injury
is determined primarily by the voltage, low voltage
GALE ENCYCLOPEDIA OF MEDICINE

can be just as dangerous as high voltage under the
right circumstances. People have been killed by
shocks of just 50 volts.
How electric shocks affect the skin is determined
by the skin’s resistance, which in turn is dependent
upon the wetness, thickness, and cleanliness of the
skin. Thin or wet skin is much less resistant than
thick or dry skin. When skin resistance is low, the
current may cause little or no skin damage but severely
burn internal organs and tissues. Conversely, high skin
resistance can produce severe skin burns but prevent
the current from entering the body.
The nervous system (the brain, spinal cord, and
nerves) is particularly vulnerable to injury. In fact,
neurological problems are the most common kind of
nonlethal harm suffered by electric shock victims.
Some neurological damage is minor and clears up on
its own or with medical treatment, but some is severe
and permanent. Neurological problems may be apparent immediately after the accident, or gradually
develop over a period of up to three years.
Damage to the respiratory and cardiovascular
systems is most acute at the moment of injury.
Electric shocks can paralyze the respiratory system
or disrupt heart action, causing instant death. Also
at risk are the smaller veins and arteries, which dissipate heat less easily than the larger blood vessels and
can develop blood clots. Damage to the smaller vessels
is probably one reason why amputation is often
required following high-voltage injuries.
Many other sorts of injuries are possible after
an electric shock, including cataracts, kidney failure,
and substantial destruction of muscle tissue. The
victim may suffer a fall or be hit by debris from
exploding equipment. An electric arc may set
clothing or nearby flammable substances on fire.
Strong shocks are often accompanied by violent
muscle spasms that can break and dislocate bones.
These spasms can also freeze the victim in place and
prevent him or her from breaking away from the
source of the current.

Diagnosis
Diagnosis relies on gathering information about
the circumstances of the accident, a thorough physical
examination, and monitoring of cardiovascular and
kidney activity. The victim’s neurological condition
can fluctuate rapidly and requires close observation.
A computed tomography scan (CT scan) or magnetic
resonance imaging (MRI) may be necessary to check
for brain injury.
1263

Electric shock injuries

Health and Human Services. 1 April 2005 <http://
www.aoa.gov/eldfam/Elder_Rights/Elder_Abuse/
Elder_Abuse_pf.asp>.
American Medical Association ‘‘Featured CSA Report:
AMA Data on Violence Between Intimates (I-00):
Elder Abuse.’’ American Medical Association January
2005 American Medical Association. 1 April 2005
<http://www.ama-assn.org/ama/pub/category/
13577.html>.
National Center on Elder Abuse ‘‘The Basics: Major Types
of Elder Abuse.’’ National Center on Elder Abuse 15
May 2003 National Center on Elder Abuse. 1 April
2005 <http://www.elderabusecenter.org/>.
National Center on Elder Abuse ‘‘Elder Abuse:
Frequently Asked questions.’’ National Center on
Elder Abuse 23 March 2005 National Center on
Elder Abuse. 1 April 2005 <http://www.
elderabusecenter.org/>.
National Committee for the Prevention of Elder Abuse ‘‘The
Role of Professionals and Concerned Citizens.’’
National Committee for the Prevention of Elder Abuse
March 2003 National Committee for the Prevention of
Elder Abuse. 1 April 2005 <http://
www.elderabusecenter.org/>.

Electrical nerve stimulation

Treatment
When an electric shock accident happens at
home or in the workplace, the main power should
immediately be shut off. If that cannot be done,
and current is still flowing through the victim, the
alternative is to stand on a dry, nonconducting
surface such as a folded newspaper, flattened cardboard carton, or plastic or rubber mat and use a
nonconducting object such as a wooden broomstick (never a damp or metallic object) to push
the victim away from the source of the current.
The victim and the source of the current must
not be touched while the current is still flowing,
for this can electrocute the rescuer. Emergency
medical help should be summoned as quickly as
possible. People who are trained to perform cardiopulmonary resuscitation (CPR) should, if appropriate, begin first aid while waiting for emergency
medical help to arrive.
Burn victims usually require treatment at a burn
center. Fluid replacement therapy is necessary to
restore lost fluids and electrolytes. Severely injured
tissue is repaired surgically, which can involve skin
grafting or amputation. Antibiotics and antibacterial
creams are used to prevent infection. Victims may
also require treatment for kidney failure. Following
surgery, physical therapy to facilitate recovery, and
psychological counseling to cope with disfigurement,
may be necessary.

Prognosis
Electric shocks cause death in 3–15% of cases.
Many survivors require amputation or are disfigured
by their burns. Injuries from household appliances
and other low-voltage sources are less likely to produce extreme damage.

KEY TERMS
Antibiotics—Substances used against microorganisms that cause infection.
Cataract—Clouding of the lens of the eye or its
capsule (surrounding membrane).
Computed tomography scan (CT scan)—A process
that uses x rays to create three-dimensional images
of structures inside the body.
Electrolytes—Substances that conduct electric current within the body and are essential for sustaining
life.
Magnetic resonance imaging (MRI)—The use of
electromagnetic energy to create images of
structures inside the body.
Skin grafting—A technique in which a piece of
healthy skin from the patient’s body (or a donor’s)
is used to cover another part of the patient’s body
that has lost its skin.

During thunderstorms, people should go indoors
immediately, even if no rain is falling, and boaters
should return to shore as rapidly as possible. People
who cannot reach indoor shelter should move away
from metallic objects such as golf clubs and fishing
rods and lie down in low-ground areas. Standing or
lying under or next to tall or metallic structures is
unsafe. An automobile is appropriate cover, as
long as the radio is off. Telephones, computers,
hair dryers, and other appliances that can act as
conduits for lightning should not be used during
thunderstorms.
Resources
BOOKS

Prevention
Parents and other adults need to be alert to possible electric dangers in the home. Damaged electric
appliances, wiring, cords, and plugs should be
repaired or replaced. Electrical repairs should be
attempted only by people with the proper training.
Hair dryers, radios, and other electric appliances
should never be used in the bathroom or anywhere
else they might accidentally come in contact with
water. Young children need to be kept away from
electric appliances and should be taught about the
dangers of electricity as soon as they are old enough.
Electric outlets require safety covers in homes with
young children.
1264

Dimick, Alan R. ‘‘Electrical Injuries.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony S.
Fauci, et al. New York: McGraw-Hill, 1997.

Howard Baker

I Electrical nerve stimulation
Definition
Electrical nerve stimulation, also called transcutaneous electrical nerve stimulation (TENS), is a
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
TENS is used to relieve pain caused by a variety of
chronic conditions, including:

KEY TERMS
Fibromyalgia—A condition characterized by
aching and stiffness, fatigue and poor sleep, as
well as tenderness at various sites on the body.
Osteoarthritis—A painful joint disease aggravated
by mechanical stress.



neck and lower back pain



headache/migraine

Phantom limb—The perception that a limb is
present (and throbbing with pain) after it has been
amputated.



arthritis

Post-herpetic neuralgia—Lingering pain that can
last for years after an attack of shingles.



post-herpetic neuralgia (lingering chronic pain after
an attack of shingles)

Sciatica—Pain that radiates along the sciatic nerve,
extending from the buttock down the leg to the foot.



sciatica (pain radiating from lower back, through the
legs, to the foot)



temporomandibular joint pain

Temporomandibular joint pain (TMJ)—Pain and
other symptoms affecting the head, jaw, and face
that are caused when the jaw joints and muscles
controlling them don’t work together correctly.



osteoarthritis



amputation (phantom limb)



fibromyalgia (a condition causing aching and stiffness throughout the body)

The device is also effective against short-term
pain, such as:


shingles (painful skin eruptions along the nerves)



bursitis (inflammation of tissue surrounding a
joint)



childbirth



post-surgical pain



fractures



muscle and joint pain



sports injuries



menstrual cramps

Description
The TENS device is a small battery-powered stimulator that produces low-intensity electrical signals
through electrodes on or near a painful area, producing a tingling sensation that reduces pain. There is no
dosage limitation, and the patient controls the amount
of pain relief.
Some experts believe TENS works by blocking
pain signals in the spinal cord, or by delivering electrical impulses to underlying nerve fibers that lessen
the experience of pain. Others suspect that the electrical stimulation triggers the release of natural painkillers in the body.
Patients can rent a TENS unit before buying one,
to see if it is effective against their pain.

Preparation
Precautions
Because TENS may interfere with pacemaker
function, patients with pacemakers should consult a
cardiologist before using a TENS unit. Patients should
also avoid electrical stimulation in the front of the
neck, which can be hazardous. The safety of the device
during pregnancy has not been established.
TENS doesn’t cure any condition; it simply
eases pain. Patients who are not sure what is causing their pain should consult a physician before
using TENS.
GALE ENCYCLOPEDIA OF MEDICINE

After TENS has been prescribed, a doctor will
refer the patient to a TENS specialist, who will explain
how to use the machine. The specialist works with the
patient to determine the settings and electrode placements for the best pain relief.

Risks
TENS is nonaddictive and completely safe. The
only side effect may be a slight skin irritation or redness in some people, which can be prevented by using
different gels or electrodes.
1265

Electrical nerve stimulation

noninvasive, drug-free pain management technique. By
sending electrical signals to underlying nerves, the
battery-powered TENS device can relieve a wide
range of chronic and acute pain.

Electrical stimulation of the brain

Normal results
The amount of relief a person gets using TENS
depends on the underlying cause of the pain, a person’s mental state, and whether or not medication is
also used. At least one study found that both a real
TENS machine and a placebo were equally effective in
reducing pain. This suggests that at least part of its
effectiveness may be due to the patient’s belief in its
ability to ease pain.
Carol A. Turkington

stimulation of the
I Electrical
brain
Definition
Electrical stimulation of the brain (ESB) is a
relatively new technique used to treat chronic pain
and tremors associated with Parkinson disease. ESB
is administered by passing an electrical current
through an electrode implanted in the brain.

Purpose
While the implantation of electrodes in the brain
is used to treat or diagnose several disorders, the term
ESB is limited here to the treatment of tremors, and
as a pain management tool for patients suffering
from back problems and other chronic injuries and
illnesses.

Precautions
An ESB tremor control device, used in treating
Parkinson patients, may interfere with or be affected
by cardiac pacemakers and other medical equipment.
As a result, patients with other implanted medical
equipment may not be good candidates for the therapy.

to the electrode in the thalamus, which inhibits or
partially relieves the tremor. The generator can be
turned on and off with a magnet, and needs to be
replaced every three to five years.
Similar methods have been used to treat chronic
pain that responded unfavorably to conventional
therapies. A remote transmitter allows these patients
to trigger electric stimulation to relieve their symptoms on an as-needed basis. Patients with failed back
syndrome, trigeminal neuropathy (pertaining to the
fifth cranial nerve), and peripheral neuropathy fared
well for pain control with this treatment, while
patients with spinal cord injury and postherpetic
neuralagia (pain along the nerves following herpes)
did poorly.

Preparation
The patient should be free of any type of infection
before undergoing an ESB procedure. He or she
may be advised to discontinue any medication for a
prescribed period of time before surgery.

Aftercare
After neurosurgery, patients should undergo
regular head dressing changes, minimize exposure to
others, and practice good personal hygiene in order
to prevent a brain infection. The head may also be kept
elevated for a prescribed period of time in order to
decrease swelling of the brain.

Risks
The implantation of electrodes into the brain
carries risks of hemorrhage, infarction, infection, and
cerebral edema. These complications could cause
irreversible neurological damage.
Patients with an implanted ESB tremor control
device may experience headaches, disequilibrium
(a disturbance of the sense of balance), burning or
tingling of the skin, or partial paralysis.

Description
Electrical stimulation of the brain, or deep brain
stimulation, is effective in treating tremor in up to
88% of Parkinson disease patients. An electrode is
implanted into the thalamus (part of the brain) of the
patient, and attached to an electric pulse generator via
an extension wire. The pulse generator is implanted
into the patient’s pectoral, or chest area, and the
extension wire is tunneled under the skin. The pulse
generator sends out intermittent electrical stimulation
1266

Normal results
ESB is effective in pain control for specific conditions. It can provide long-term pain relief with few side
effects or complications.
For the control of tremors a deep brain stimulator
does provide some relief. It is recommended for
patients with tremors severe enough to affect their
quality of life.
GALE ENCYCLOPEDIA OF MEDICINE

Electrocardiography

KEY TERMS
Infarction—A sudden insuffiency of local blood
supply.
Neuralgia—Pain extending along one or more
nerves.
Neuropathy—A functional disturbance or change
in the nervous system.
Parkinson disease—A chronic neurological illness
that causes tremors, stiffness, and difficulty in
moving and walking.
An EKG strip indicting atrial flutter. (Custom Medical Stock
Photo. Reproduced by permission.)

Resources

evaluate causes of symptoms such as chest pain, shortness of breath, and palpitations.

OTHER

The Parkinson’s Web.<http://pdweb.mgh.harvard.edu>.
University of Southern California. The
ANGELN eurosurgical Information Resource. <http://
www.usc.edu/hsc/neurosurgery/angel.html>.

Paula Anne Ford-Martin

I Electrocardiography
Definition
Electrocardiography is a commonly used, noninvasive procedure for recording electrical changes
in the heart. The record, which is called an electrocardiogram (ECG or EKG), shows the series of
waves that relate to the electrical impulses which
occur during each beat of the heart. The results are
printed on paper or displayed on a monitor. The
waves in a normal record are named P, Q, R, S,
and T and follow in alphabetical order. The number of waves may vary, and other waves may be
present.

Purpose
Electrocardiography is a starting point for detecting many cardiac problems. It is used routinely in
physical examinations and for monitoring the
patient’s condition during and after surgery, as well
as during intensive care. It is the basic measurement
used for tests such as exercise tolerance. It is used to
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
No special precautions are required.

Description
The patient disrobes from the waist up, and electrodes (tiny wires in adhesive pads) are applied to
specific sites on the arms, legs, and chest. When
attached, the electrodes are called leads; three to 12
leads may be employed.
Muscle movement may interfere with the recording, which lasts for several beats of the heart. In
cases where rhythm disturbances are suspected to
be infrequent, the patient may wear a small Holter
monitor in order to record continuously over a
24-hour period; this is known as ambulatory
monitoring.

Preparation
The skin is cleaned to obtain good electrical contact at the electrode positions.

Aftercare
To avoid skin irritation from the salty gel used to
obtain good electrical contact, the skin should be
thoroughly cleaned after removal of the electrodes.

Risks
No complications from this procedure have been
observed.
1267

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1268

The heart is described as showing arrhythmia or
dysrhythmia when time intervals between waves, the
order, or the number of waves do not fit this pattern.

When the presence of all waves is observed in the
electrocardiogram and these waves follow the order
defined alphabetically, the heart is said to show a
normal sinus rhythm, and impulses may be assumed
to be following the regular conduction pathway.

When the heart is operating normally, each part
contracts in a specific order. Contraction of the
muscle is triggered by an electrical impulse. These
electrical impulses travel through specialized cells
that form a conduction system. Following this
pathway ensures that contractions will occur in a
coordinated manner.

Normal results

A patient undergoing electrocardiography. (Russell Curtis,
Photo Researchers. Reproduced by permission.)

This EKG strip shows evidence of Wolff-Parkinson-White
syndrome. (Custom Medical Stock Photo. Reproduced by
permission.)

,I

Electrocardiography

GALE ENCYCLOPEDIA OF MEDICINE

When the atrial impulse fails to reach the ventricle, a condition known as heart block results. If this is
partial, the P-R interval (the time for the impulse to

The varied sources of dysrhythmias provide a
wide range of alterations in the form of the electrocardiogram. Ectopic beats that start in the ventricle
display an abnormal QRS complex. This can indicate
disease associated with insufficient blood supply to
the muscle (myocardial ischemia). Multiple ectopic
sites lead to rapid and uncoordinated contractions of
the atria or ventricles. This condition is known as
fibrillation. In atrial fibrillation, P waves are absent,
and the QRS complex appears at erratic intervals, or
‘‘irregularly irregular.’’

The cause of dysrhythmia is ectopic beats.
Ectopic beats are premature heart beats that arise
from a site other than the sinus node–commonly
from the atria, atrioventricular node, or the ventricle. When these dysrhythmias are only occasional,
they may produce no symptoms, or a feeling of the
heart turning over or ‘‘flip-flopping’’ may be experienced. These occasional dysrhythmias are common
in healthy people, but they also can be an indication
of heart disease.

Special training is required for interpretation of
the electrocardiogram. To summarize the features
used in interpretations in the simplest manner, the
P wave of the electrocardiogram is associated with
the contraction of the atria. The QRS series of waves,
or QRS complex, is associated with ventricular
contraction, with the T wave coming after the contraction. Finally, the P-Q or P-R interval gives a
value for the time taken for the electrical impulse to
travel from the atria to the ventricle (normally less
than 0.2 sec).

Abnormal results

In the normal heart, electrical impulses–at a rate
of 60–100 times per minute–originate in the sinus
node. The sinus node is located in the first chamber,
known as the right atrium, where blood re-enters the
heart. After traveling down to the junction between
the upper and lower chambers, the signal stimulates
the atrioventricular node. From here, after a delay,
it passes by specialized routes through the lower
chambers or ventricles. In many disease states, the
passage of the electrical impulse can be interrupted
in a variety of ways, causing the heart to perform less
efficiently.

Other features that may be altered include the direction of wave deflection and wave widths.

Ambulatory monitoring—ECG recording over a
prolonged period during which the patient can
move around.
Arrhythmia or dysrhythmia—Abnormal rhythm in
hearts that contract in an irregular way.
ECG or EKG—A record of the waves that relates
to the electrical impulses produced at each beat of
the heart.
Electrodes—Tiny wires in adhesive pads that are
applied to the body for ECG measurement.
Fibrillation—Rapid, uncoordinated contractions of
the upper or the lower chambers of the heart.
Lead—Name given the electrode when it is
attached to the skin.

The purpose of electroconvulsive therapy is to provide relief from the signs and symptoms of mental
illnesses such as severe depression, mania, and schizophrenia. ECT is indicated when patients need rapid
improvement because they are suicidal, self-injurious,
refuse to eat or drink, cannot or will not take medication
as prescribed, or present some other danger to themselves. Antidepressant medications, while effective in
many cases, may take two–six weeks to produce a therapeutic effect. Antipsychotic medications used to treat
mania and schizophrenia have many uncomfortable and
sometimes dangerous side effects, limiting their use. In
addition, some patients develop allergies and therefore
are unable to take their medicine.

Precautions
The most common risks associated with ECT are
disturbances in heart rhythm. Broken or dislocated
bones occur very rarely.

reach the ventricle) is prolonged. If complete, the
ventricles beat independently of the atria at about 40
beats per minute, and the QRS complex is mostly
dissociated from the P wave.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Alison M. Grant

I Electroconvulsive therapy
Definition
Electroconvulsive therapy (ECT) is a medical
treatment for severe mental illness in which a small,
carefully controlled amount of electricity is introduced
into the brain. This electrical stimulation, used in
conjunction with anesthesia and muscle relaxant
medications, produces a mild generalized seizure or
convulsion. While used to treat a variety of psychiatric
disorders, it is most effective in the treatment of severe
depression, and provides the most rapid relief currently available for this illness.

GALE ENCYCLOPEDIA OF MEDICINE

Description
The treatment of severe mental illness, such as
schizophrenia, using electroconvulsive therapy was
introduced in 1938 by two Italian doctors named
Cerletti and Bini. In those days many doctors believed
that convulsions were incompatible with schizophrenia since, according to their obervations, this disease
rarely occurred in individuals suffering from epilepsy.
They concluded, therefore, that if convulsions could
be artifically produced in patients with schizophrenia,
the illness could be cured. Some doctors were already
using a variety of chemicals to produce seizures, but
many of their patients died or suffered severe injuries
because the strength of the convulsions could not be
well controlled.
Electroconvulsive therapy is among the most
controversial of all procedures used to treat mental
illness. When it was first introduced, many people
were frightened simply because it was called ‘‘shock
treatment.’’ Many assumed the procedure would be
painful, others thought it was a form of electrocution, and still others believed it would cause brain
damage. Unfortunately, unfavorable publicity
in newspapers, magazines, and movies added to
these fears.
Indeed, in those early years, patients and families
were rarely educated by doctors and nurses regarding
this or other forms of psychiatric treatment. In addition,
no anesthesia or muscle relaxants were used. As a result,

1269

Electroconvulsive therapy

Purpose

KEY TERMS

Electroconvulsive therapy

patients had violent seizures, and even though they did
not remember them, the procedure itself was frightening.
The way these treatments are given today is very
different from the procedures used in the past. Currently,
ECT is offered on both an inpatient and outpatient basis.
Hospitals have specially equipped rooms with oxygen,
suction, and cardiopulmonary resuscitation (CPR) in
order to deal with the rare emergency.
The treatment is carried out as follows: approximately 30 minutes before the scheduled treatment
time, the patient may receive an injection of a medication (such as atropine) that keeps the pulse rate
from decreasing too much during the convulsion.
Next, the patient is placed on a cot and hooked up to
a machine that automatically takes and displays
vital signs (temperature, pulse, respiration, and
blood pressure) on a television-like monitor. A mild
anesthetic is then injected into a vein, followed by a
medication (such a Anectine) that relaxes all of the
muscles in the body so that the seizure is mild, and the
risk of broken bones is virtually eliminated.
When the patient is both relaxed and asleep, an
airway is placed in the mouth to aid with breathing.
Electrodes are placed on the sides of the head in the
temple areas. An electric current is passed through the
brain by means of a machine specifically designed for
this purpose. The usual dose of electricity is 70–150
volts for 0.1–0.5 seconds. In the first stage of the
seizure (tonic phase), the muscles in the body that
have not been paralyzed by medication contract for a
period of five to 15 seconds. This is followed by the
second stage (clonic phase) that is characterized by
twitching movements, usually visible only in the
toes or in a non-paralyzed arm or leg. These are caused
by alternating contraction and relaxation of these
same muscles. This stage lasts approximately 10–60
seconds. The entire procedure, from beginning to
end, lasts about 30 minutes.
The total number of treatments a patient will receive
depends upon many factors such as age, diagnosis, the
history of illness, family support, and response to therapy. Patients with depression, for example, usually
require six to 12 treatments. Treatments are usually
administered every other day, three times a week.
The electrodes may be placed on both sides of
the head (bilateral) or one side (unilateral). While
bilateral ECT appears to be somewhat more effective, unilateral ECT is preferred for individuals
who experience prolonged confusion or forgetfulness
following treatment. Many doctors begin treatment
with unilateral ECT, then change to bilateral if the
patient is not improving.
1270

Post-treatment confusion and forgetfulness are
common, though disturbing symptoms associated
with ECT. Doctors and nurses must be patient and
supportive by providing patients with factual information about recovery. Elderly patients, for example,
may become increasingly confused and forgetful
as the treatments continue. These symptoms usually
subside with time, but a small minority of patients
state that they have never fully recovered from these
effects.
With the introduction of antipsychotics in the
1950s, the use of ECT became less frequent. These
new medications provided relief for untold thousands
of patients who suffered greatly from their illness.
However, there are a number of side effects associated
with these drugs, some of which are irreversible.
Another drawback is that some medications do not
produce a therapeutic effect for two–six weeks. During
this time the patient may present a danger to himself
or others. In addition, there are patients who do not
respond to medicine or who have severe allergic
reactions. For these individuals, ECT may be the
only treatment that will help.

Preparation
Patients and relatives are prepared for ECT by
being shown video tapes that explain both the procedure and the risks involved. The physician then
answers any questions these individuals may have,
and the patient is asked to sign an ‘‘Informed
Consent Form.’’ This gives the doctor and the hospital
permission to administer the treatment.
Once the form is signed, the doctor performs a
complete physical examination, and orders a number
of tests that can help identify any potential problem.
These tests may include a chest x ray, an electrocardiogram (ECG), urinalysis, spinal x ray, brain wave
(EEG), and complete blood count (CBC).
Some medications, such as lithium and a type of
antidepressant known as monoamine oxidase inhibitors, should be discontinued for some time before
treatment. Patients are instructed not to eat or drink
for at least eight hours prior to the procedure in order
to reduce the possibility of vomiting and choking.

Aftercare
After the treatment, patients are moved to a
recovery area. Vital signs are recorded every five minutes until the patient is fully awake, which may take
15–30 minutes. Some initial confusion may be present
but usually disappears in a matter of minutes. There
GALE ENCYCLOPEDIA OF MEDICINE

Mania—A mood disorder in which a person experiences prolonged elation or irritability characterized by overactivity that can lead to exhaustion
and medical emergencies.
Relapse—A return of the signs and symptoms of an
illness.
Schizophrenia—A severe mental illness in which a
person has difficulty distinguishing what is real
from what is not real. It is often characterized by
hallucinations, delusions, and withdrawal from
people and social activities.

may be complaints of headache, muscle pain, or back
pain. Such discomfort is quickly relieved by mild medications such as aspirin.

Risks
Advanced medical technology has substantially
reduced the complications associated with ECT.
These include slow heart beat (bradycardia), rapid
heart beat (tachycardia), memory loss, and confusion.
Persons at high risk for ECT include those with recent
heart attack, uncontrolled blood pressure, brain
tumors, and previous spinal injuries.

National Institutes of Health. 5600 Fishers Lane. Room
7CO2, Rockville, MD 20857. (301) 496-4000. <http://
www.nih.gov>.

Donald G. Barstow, RN

Electrocution see Electric shock injuries

I Electroencephalography
Definition
Electroencephalography, or EEG, is a neurological test that uses an electronic monitoring device to
measure and record electrical activity in the brain.

Purpose
The EEG is a key tool in the diagnosis and
management of epilepsy and other seizure disorders.
It is also used to assist in the diagnosis of brain damage
and disease (e.g., stroke, tumors, encephalitis), mental
retardation, sleep disorders, degenerative diseases
such as Alzheimer’s disease and Parkinson’s disease,
and certain mental disorders (e.g., alcoholism, schizophrenia, autism).
An EEG may also be used to monitor brain
activity during surgery and to determine brain death.

Normal results
ECT often produces dramatic improvement in the
signs and symptoms of major depression, especially in
elderly individuals, sometimes during the first week of
treatment. While it is estimated that 50% of these
patients will experience a future return of symptoms,
the prognosis for each episode of illness is good. Mania
also often responds well to treatment. The picture is not
as bright for schizophrenia, which is more difficult to
treat and is characterized by frequent relapses.
A few patients are placed on maintenance ECT.
This means they return to the hospital every one–two
months, as needed, for an additional treatment. These
individuals are thus able to keep their illness under
control and lead a normal and productive life.
Resources
BOOKS

Stuart, Gail W., and Michele T. Laraia. Principles and
Practice of Psychiatric Nursing. St. Louis: Mosby-Year
Book, Inc., 1998.
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Electroencephalography should be administered
and interpreted by a trained medical professional
only. Data from an EEG is only one element of a
complete medical and/or psychological patient assessment, and should never be used alone as the sole basis
for a diagnosis.

Description
Before the EEG begins, a nurse or technician
attaches approximately 16–20 electrodes to the
patient’s scalp with a conductive, washable paste.
Depending on the purpose for the EEG, implantable
or invasive electrodes are occasionally used.
Implantable electrodes include sphenoidal electrodes,
which are fine wires inserted under the zygomatic
arch, or cheekbone; and depth electrodes, which
are surgically-implanted into the brain. The EEG
electrodes are painless, and are used to measure the
electrical activity in various regions of the brain.
1271

Electroencephalography

ORGANIZATIONS

KEY TERMS

Electroencephalography
This woman is undergoing an electroencephalogram (EEG) to diagnose Alzheimer’s disease. On the computer screen at the
right are the colored scans of the electrical activity in her brain. Alzheimer’s patients show a specific abnormality in their EEGs.
(Photograph by Catherine Pouedras, Photo Researchers, Inc. Reproduced by permission.)

For the test, the patient lies on a bed, padded table,
or comfortable chair and is asked to relax and remain
still during the EEG testing period. An EEG usually
takes no more than one hour. During the test procedure,
the patient may be asked to breathe slowly or quickly;
visual stimuli such as flashing lights or a patterned
board may be used to stimulate certain types of brain
activity. Throughout the procedure, the electroencephalograph machine makes a continuous graphic record of
the patient’s brain activity, or brainwaves, on a long
strip of recording paper or on a computer screen. This
graphic record is called an electroencephalogram.
The sleep EEG uses the same equipment and
procedures as a regular EEG. Patients undergoing a
sleep EEG are encouraged to fall asleep completely
rather than just relax. They are typically provided a
bed and a quiet room conducive to sleep. A sleep
EEG lasts up to three hours.
In an ambulatory EEG, patients are hooked up to
a portable cassette recorder. They then go about their
normal activities, and take their normal rest and sleep
for a period of up to 24 hours. During this period, the
1272

patient and patient’s family record any symptoms or
abnormal behaviors, which can later be correlated
with the EEG to see if they represent seizures.
Many insurance plans provide reimbursement for
EEG testing. Costs for an EEG range from $100 to
more than $500, depending on the purpose and type of
test (i.e., asleep or awake, and invasive or non-invasive
electrodes). Because coverage may be dependent on
the disorder or illness the EEG is evaluating, patients
should check with their individual insurance plan.

Preparation
Full instructions should be given to EEG patients
when they schedule their test. Typically, individuals on
medications that affect the central nervous system,
such as anticonvulsants, stimulants, or antidepressants, are told to discontinue their prescription for a
short time prior to the test (usually one to two days).
Patients may be asked to avoid food and beverages
that contain caffeine, a central nervous system
stimulant. However, any such request should be
GALE ENCYCLOPEDIA OF MEDICINE

Epilepsy—A neurological disorder characterized
by recurrent seizures with or without a loss of
consciousness.
Ictal EEG—Used to measure brain activity during a
seizure. May be useful in learning more about
patients who aren’t responding to conventional
treatments.

cleared by the treating physician. Patients may also be
asked to arrive for the test with clean hair free of spray
or other styling products.
Patients undergoing a sleep EEG may be asked to
remain awake the night before their test. They may be
given a sedative prior to the test to induce sleep.

Aftercare
If the patient has suspended regular medication
for the test, the EEG nurse or technician should advise
him when he can begin taking it again.

have a delta wave pattern of under four cycles per
second.

Abnormal results
The EEG readings of patients with epilepsy or
other seizure disorders display bursts or spikes of
electrical activity. In focal epilepsy, spikes are
restricted to one hemisphere of the brain. If spikes
are generalized to both hemispheres of the brain,
multifocal epilepsy may be present.
The diagnostic brainwave patterns of other disorders varies widely. The appearance of excess theta
waves (four to eight cycles per second) may indicate
brain injury. Brain wave patterns in patients with
brain disease, mental retardation, and brain injury
show overall slowing. A trained medical specialist
should interpret EEG results in the context of the
patient’s medical history, and other pertinent medical
test results.
Resources
BOOKS

Restak, Richard M. Brainscapes: An Introduction to What
Neuroscience Has Learned About the Structure,
Function, and Abilities of the Brain. NewYork:
Hyperion, 1995.

Risks
Being off medication for one–two days may
trigger seizures. Certain procedures used during EEG
may trigger seizures in patients with epilepsy. Those
procedures include flashing lights and deep breathing.
If the EEG is being used as a diagnostic for epilepsy
(i.e., to determine the type of seizures an individual is
suffering from), this may be a desired effect, although
the patient needs to be monitored closely so that the
seizure can be aborted if necessary. This type of test is
known as an ictal EEG.

Normal results
In reading and interpreting brainwave patterns, a
neurologist or other physician will evaluate the type of
brainwaves and the symmetry, location, and consistency of brainwave patterns. He will also look at the
brainwave response to certain stimuli presented
during the EEG test (such as flashing lights or noise).
There are four basic types of brainwaves: alpha, beta,
theta, and delta. ‘‘Normal’’ brainwave patterns vary
widely, depending on factors of age and activity. For
example, awake and relaxed individuals typically
register an alpha wave pattern of eight to 13 cycles
per second. Young children and sleeping adults may
GALE ENCYCLOPEDIA OF MEDICINE

Paula Anne Ford-Martin

I Electrolyte disorders
Definition
An electrolyte disorder is an imbalance of certain
ionized salts (i.e., bicarbonate, calcium, chloride, magnesium, phosphate, potassium, and sodium) in the
blood.

Description
Electrolytes are ionized molecules found throughout the blood, tissues, and cells of the body. These
molecules, which are either positive (cations) or negative (anions), conduct an electric current and help to
balance pH and acid-base levels in the body.
Electrolytes also facilitate the passage of fluid between
and within cells through a process known as osmosis
and play a part in regulating the function of the neuromuscular, endocrine, and excretory systems.
1273

Electrolyte disorders

KEY TERMS

Electrolyte disorders

The serum electrolytes include:




Sodium (Na). A positively charged electrolyte that
helps to balance fluid levels in the body and facilitates neuromuscular functioning.
Potassium (K). A main component of cellular fluid,
this positive electrolyte helps to regulate neuromuscular function and osmotic pressure.



Calcium (Ca). A cation, or positive electrolyte, that
affects neuromuscular performance and contributes
to skeletal growth and blood coagulation.



Magnesium (Mg). Influences muscle contractions
and intracellular activity. A cation.



Chloride (CI). An anion, or negative electrolyte, that
regulates blood pressure.



Phosphate (HPO4). Negative electrolyte that
impacts metabolism and regulates acid-base balance
and calcium levels.



Bicarbonate (HCO3). A negatively charged electrolyte that assists in the regulation of blood pH levels.
Bicarbonate insufficiencies and elevations cause
acid-base disorders (i.e., acidosis, alkalosis).

Medications, chronic diseases, and trauma (for
example, burns, or fractures etc.) may cause the concentration of certain electrolytes in the body to become
too high (hyper-) or too low (hypo-). When this happens, an electrolyte imbalance, or disorder, results.

Causes and symptoms
Sodium
HYPERNATREMIA. Sodium helps the kidneys to
regulate the amount of water the body retains or
excretes. Consequently, individuals with elevated
serum sodium levels also suffer from a loss of fluids,
or dehydration. Hypernatremia can be caused by
inadequate water intake, excessive fluid loss (i.e.,
diabetes insipidus, kidney disease, severe burns, and
prolonged vomiting or diarrhea), or sodium retention
(caused by excessive sodium intake or aldosteronism).
In addition, certain drugs, including loop diuretics,
corticosteroids, and antihypertensive medications
may cause elevated sodium levels.



irregular heartbeat (tachycardia)



irritability



fatigue



lethargy



heavy, labored breathing



muscle twitching and/or seizures

HYPONATREMIA. Up to 1% of all hospitalized
patients and as many as 18% of nursing home patients
develop hyponatremia, making it one of the most
common electrolyte disorders. A 2004 study questioned the routine make-up of fluids prescribed for
children and delivered intravenously (through a
needle into a vein) in hospitals today. The authors
recommended only using IV fluids when necessary
and then using isotonic saline. Diuretics, certain
psychoactive drugs (i.e., fluoxetine, sertraline, haloperidol), specific antipsychotics (lithium), vasopressin,
chlorpropamide, the illicit drug ‘‘ecstasy,’’ and other
pharmaceuticals can cause decreased sodium levels,
or hyponatremia. Low sodium levels may also be
triggered by inadequate dietary intake of sodium,
excessive perspiration, water intoxication, and impairment of adrenal gland or kidney function.

Symptoms of hyponatremia include:


nausea, abdominal cramping, and/or vomiting



headache



edema (swelling)



muscle weakness and/or tremor



paralysis



disorientation



slowed breathing



seizures



coma
Potassium



thirst



orthostatic hypotension



dry mouth and mucous membranes

HYPERKALEMIA. Hyperkalemia may be caused by
ketoacidosis (diabetic coma), myocardial infarction
(heart attack), severe burns, kidney failure, fasting,
bulimia nervosa, gastrointestinal bleeding, adrenal
insufficiency, or Addison’s disease. Diuretic drugs,
cyclosporin, lithium, heparin, ACE inhibitors, beta
blockers, and trimethoprim can increase serum
potassium levels, as can heavy exercise. The condition
may also be secondary to hypernatremia (low serum
concentrations of sodium). Symptoms may include:



dark, concentrated urine



weakness



loss of elasticity in the skin



nausea and/or abdominal pain

Symptoms of hypernatremia include:

1274

GALE ENCYCLOPEDIA OF MEDICINE

irregular heartbeat (arrhythmia)



mood changes (depression, irritability)



diarrhea



dry skin



muscle pain



brittle nails



facial twitching

HYPOKALEMIA. Severe dehydration, aldosteronism,
Cushing’s syndrome, kidney disease, long-term diuretic
therapy, certain penicillins, laxative abuse, congestive
heart failure, and adrenal gland impairments can all
cause depletion of potassium levels in the bloodstream.
A substance known as glycyrrhetinic acid, which is found
in licorice and chewing tobacco, can also deplete potassium serum levels. Symptoms of hypokalemia include:

Electrolyte disorders



Magnesium
HYPERMAGNESEMIA. Excessive magnesium levels
may occur with end-stage renal disease, Addison’s
disease, or an overdose of magnesium salts.
Hypermagnesemia is characterized by:



weakness



lethargy



paralysis



hypotension



increased urination



decreased heart and respiratory rate



irregular heartbeat (arrhythmia)



muscle weakness



orthostatic hypotension



diminished tendon reflexes



muscle pain



tetany

HYPOMAGNESEMIA. Inadequate dietary intake of
magnesium, often caused by chronic alcoholism or
malnutrition, is a common cause of hypomagnesemia.
Other causes include malabsorption syndromes, pancreatitis, aldosteronism, burns, hyperparathyroidism,
digestive system disorders, and diuretic use.
Symptoms of low serum magnesium levels include:

Calcium
HYPERCALCEMIA. Blood calcium levels may be elevated in cases of thyroid disorder, multiple myeloma,
metastatic cancer, multiple bone fractures, milk-alkali
syndrome, and Paget’s disease. Excessive use of
calcium-containing supplements and certain overthe-counter medications (i.e., antacids) may also cause
hypercalcemia. In infants, lesser known causes may
include blue diaper syndrome, Williams syndrome,
secondary hyperparathyroidism from maternal hypocalcemia, and dietary phosphate deficiency. Symptoms
include:


fatigue



constipation



depression



confusion



muscle pain



nausea and vomiting



dehydration



increased urination



irregular heartbeat (arrhythmia)
HYPOCALCEMIA. Thyroid disorders, kidney fail-

ure, severe burns, sepsis, vitamin D deficiency, and
medications such as heparin and glucogan can deplete
blood calcium levels. Lowered levels cause:


muscle cramps and spasms



tetany and/or convulsions

GALE ENCYCLOPEDIA OF MEDICINE



leg and foot cramps



weight loss



vomiting



muscle spasms, twitching, and tremors



seizures



muscle weakness



arrthymia
Chloride

HYPERCHLOREMIA. Severe dehydration, kidney
failure, hemodialysis, traumatic brain injury, and
aldosteronism can also cause hyperchloremia. Drugs
such as boric acid and ammonium chloride and the
intravenous (IV) infusion of sodium chloride can also
boost chloride levels, resulting in hyperchloremic
metabolic acidosis. Symptoms include:


weakness



headache



nausea



cardiac arrest

HYPOCHLOREMIA. Hypochloremia usually occurs
as a result of sodium and potassium depletion (i.e.,
hyponatremia, hypokalemia). Severe depletion of

1275

Electrolyte disorders

serum chloride levels causes metabolic alkalosis. This
alkalization of the bloodstream is characterized by:


mental confusion



slowed breathing



paralysis



muscle tension or spasm
Phosphate
HYPERPHOSPHATEMIA. Skeletal fractures or dis-

ease, kidney failure, hypoparathyroidism, hemodialysis,
diabetic ketoacidosis, acromegaly, systemic infection,
and intestinal obstruction can all cause phosphate
retention and build-up in the blood. The disorder
occurs concurrently with hypocalcemia. Individuals
with mild hyperphosphatemia are typically asymptomatic, but signs of severe hyperphosphatemia include:


tingling in hands and fingers



muscle spasms and cramps



convulsions



cardiac arrest

HYPOPHOSPHATEMIA. Serum phosphate levels of
2 mg/dL or below may be caused by hypomagnesemia
and hypokalemia. Severe burns, alcoholism, diabetic
ketoacidosis, kidney disease, hyperparathyroidism, hypothyroidism, Cushing’s syndrome, malnutrition, hemodialysis, vitamin D deficiency, and prolonged diuretic therapy
can also diminish blood phosphate levels. There are
typically few physical signs of mild phosphate depletion.
Symptoms of severe hypophosphatemia include:


muscle weakness



weight loss



bone deformities (osteomalacia)

Diagnosis
Diagnosis is performed by a physician or other qualified healthcare provider who will take a medical history,
discuss symptoms, perform a complete physical examination, and prescribe appropriate laboratory tests. Because
electrolyte disorders commonly affect the neuromuscular
system, the provider will test reflexes. If a calcium imbalance is suspected, the physician will also check for
Chvostek’s sign, a reflex test that triggers an involuntary
facial twitch, and Trousseau’s sign, a muscle spasm that
occurs in response to pressure on the upper arm.
Serum electrolyte imbalances can be detected
through blood tests. Blood is drawn from a vein on
the back of the hand or inside of the elbow by a medical
technician, or phlebotomist, and analyzed at a lab.
1276

Normal levels of electrolytes are:


Sodium. 135–145 mEq/L (serum)



Potassium. 3.5–5.5 mEq/L (serum)



Calcium. 8.8–10.4 mg/dL (total Ca; serum);
4.7–5.2 mg/dL (unbound Ca; serum)



Magnesium. 1.4–2.1 mEq/L (plasma)



Chloride. 100–108 mEq/L (serum)



Phosphate. 2.5–4.5 mg/dL (plasma; adults)

Standard ranges for test results may vary due to
differing laboratory standards and physiological variances (gender, age, and other factors). Other blood
tests that determine pH levels and acid-base balance
may also be performed.

Treatment
Treatment of electrolyte disorders depends on the
underlying cause of the problem and the type of electrolyte involved. If the disorder is caused by poor diet
or improper fluid intake, nutritional changes may be
prescribed. If medications such as diuretics triggered
the imbalance, discontinuing or adjusting the drug
therapy may effectively treat the condition. Fluid
and electrolyte replacement therapy, either intravenously or by mouth, can reverse electrolyte depletion.
Hemodialysis treatment may be required to
reduce serum potassium levels in hyperkalemic
patients with impaired kidney function. It may also
be recommended for renal patients suffering from
severe hypermagnesemia.

Prognosis
A patient’s long-term prognosis depends upon the
root cause of the electrolyte disorder. However, when
treated quickly and appropriately, electrolyte imbalances in and of themselves are usually effectively
reversed.
When they are mild, some electrolyte imbalances
have few to no symptoms and may pass unnoticed.
For example, transient hyperphosphatemia is usually
fairly benign. However, long-term elevations of blood
phosphate levels can lead to potentially fatal soft tissue and vascular calcifications and bone disease, and
severe serum phosphate deficiencies (hypophosphatemia) can cause encephalopathy, coma, and death.
Severe hypernatremia has a mortality rate of
40–60%. Death is commonly due to cerebrovascular
damage and hemorrhage resulting from dehydration
and shrinkage of the brain cells.
GALE ENCYCLOPEDIA OF MEDICINE

Acid-base balance—A balance of acidity and
alkalinity of fluids in the body that keeps the pH
level of blood around 7.35–7.45.
Aldosteronism—A condition defined by high
serum levels of aldosterone, a hormone secreted
by the adrenal gland that is responsible for increasing sodium reabsorption in the kidneys.
Addison’s disease—A disease characterized by a
deficiency in adrenocortical hormones due to
destruction of the adrenal gland.
Bulimia nervosa—An eating disorder characterized by binging and purging (self-induced vomiting) behaviors.
Milk-alkali syndrome—Elevated blood calcium
levels and alkalosis caused by excessive intake of
milk and alkalis. Usually occurs in the treatment of
peptic ulcer.
Orthostatic hypotension—A drop in blood pressure that causes faintness or dizziness and occurs
when one rises to a standing position. Also known
as postural hypotension.
Osmotic pressure—Pressure that occurs when two
solutions of differing concentrations are separated
by a semipermeable membrane, such as a cellular
wall, and the lower concentration solute is drawn
across the membrane into the higher concentration
solute (osmosis).
Tetany—A disorder of the nervous system characterized by muscle cramps, spasms of the arms and
legs, and numbness of the extremities.

Prevention
Physicians should use caution when prescribing
drugs known to affect electrolyte levels and acid-base
balance. Individuals with kidney disease, thyroid problems, and other conditions that may place them at
risk for developing an electrolyte disorder should be
educated on the signs and symptoms.
Resources
BOOKS

Post, Theodore, and Burton Rose. Clinical Physiology of
Acid-Base and Electrolyte Disorders. 5th ed. New York:
McGraw-Hill Professional, 2001.
PERIODICALS

Cohn, Jay N., et al. ‘‘New Guidelines for Potassium
Replacement in Clinical Practice: A Contemporary
GALE ENCYCLOPEDIA OF MEDICINE

Review by the National Council on Potassium in
Clinical Practice.’’ Archives of Internal Medicine 160,
no.16 (September 11, 2000): 2429-36.
Goh, Kian Ping. ‘‘Management of Hyponatremia.’’
American Family Physician May 15, 2004: 2387.
Moritz, Michael L., Juan Carlos Ayus. ‘‘Hospital-acquired
Hyponatremia: Why are There Still Deaths?’’ Pediatrics
May 2004: 1395–1397.
Springate, James E., Mary F. Carroll. ‘‘HAdditional Causes
of Hypercalcemia in Infants.’’ American Family
Physician June 15, 2004: 2766.

Paula Anne Ford-Martin
Teresa G. Odle

I Electrolyte supplements
Definition
Electrolyte supplements are a varied group of
prescription and nonprescription preparations used
to correct imbalances in the body’s electrolyte levels.
Electrolytes themselves are substances that dissociate
into ions (electrically charged atoms or atom groups)
when they melt or are dissolved, thus serving to conduct electricity. In the human body, electrolytes are
thus critical to the proper distribution of water, muscle
contraction and expansion, transmission of nerve
impulses, delivery of oxygen to body tissues, heart
rate and rhythm, acid-base balance, and other important functions or conditions.
The ions that are formed when electrolytes are
dissolved in body fluids are either positively or negatively charged. Positively charged ions are called
cations, and are formed when an atom or atom
group loses electrons. The most important cations in
the human body are sodium, potassium, magnesium,
and calcium ions. Negatively charged ions are called
anions, and are formed when an atom or atom group
gains electrons. The principal anions in the body
include bicarbonate, chloride, phosphate, and sulfate
ions, as well as ions formed by certain protein
compounds or organic acids.
About 60 percent of an adult human male’s total
body weight is water. In adult women, the figure is
about 55 percent, and is even lower in the elderly and
in obese people. Two-thirds of total body water
(TBW) lies inside cells and is known as intracellular
fluid or ICF. The remaining third of TBW lies outside
the cells and is called extracellular fluid or ECF. About 75
percent of ECF lies in connective tissue or the spaces
between tissues outside the blood vessels (interstitial
1277

Electrolyte supplements

KEY TERMS

Electrolyte supplements

spaces), while the remaining 25 percent is within the
blood vessels. In addition to representing different proportions of TBW, ICF and ECF differ significantly in
their electrolyte content. Whereas the major cation in
ICF is potassium, the most important cation in ECF is
sodium. These differences in electrolyte levels help to
regulate the movement of water between ICF and ECF.
Children are more vulnerable than adults to fluid
and electrolyte imbalances, in part because they have
different ratios of TBW to total body weight, and of
ICF to ECF. A newborn baby carried to full term has
a TBW ratio between 75 and 80 percent. The baby’s
total body water ratio decreases by 4– 5 percent during
the first week after birth and reaches the adult level of
60 percent by twelve months of age. Similarly, a newborn has an ICF: ECF ratio of 55: 45, which falls to the
adult ratio of 70: 30 during the first year of life. In
addition to these different fluid ratios, children’s kidneys are less efficient than adults in regulating water
balance; children have smaller organ systems that dissipate body heat less efficiently; and their core body
temperature rises faster than that of an adult when
they become dehydrated. All these factors help to
explain why some electrolyte supplements are formulated specifically for children.

Purpose
The purpose of electrolyte supplements is to
restore the proper ratio of total body water to total
body weight and the correct proportions of the various
electrolytes in body fluids. Electrolyte imbalances may
result from excessive intake or inadequate elimination
of electrolytes on the one hand or by insufficient
intake or excessive elimination on the other hand.
Body regulation of water and electrolytes
Under normal conditions, the water and electrolyte content of the body is regulated by the kidneys, the
secretion of antidiuretic hormone, and the sensation
of thirst. The average adult needs to take in about
700–800 mL (about 1.5–1.7 pints) of water per day in
order to match the water lost through perspiration,
breathing, and excretion of waste products. The water
that is taken in by mouth is added to the 200–300 mL
(0.42–0.63 pints) of water that are formed in the body
each day through tissue breakdown.
The amount of water needed to match fluid losses,
however, may be considerably greater than the average
during exercise or in patients with fever, severe vomiting,
or diarrhea. Adults with fever typically lose an additional
.75–1.0 ounces of fluid per day for each degree that their
temperature rises above normal. With regard to
1278

diarrhea, adults with cholera have been reported to lose
as much as a quart of fluid per hour in their stools. The
fluid lost in this way also contains sodium, potassium,
and chloride, resulting in electrolyte imbalances in cholera patients as well as dehydration.
Exercise raises the total metabolism of the body to
5–15 times the resting rate. Most of this energy (70–90
percent) is released as heat, which is partially dissipated by the evaporation of sweat. Depending on
weather conditions, the type and weight of clothing
being worn, and the intensity of exercise or physical
work performed, adults may lose anywhere from 1 to
2.5 quarts of fluid per hour through perspiration.
Sweat, however, contains sodium chloride as well as
smaller amounts of potassium, calcium, and magnesium. In order to maintain the proper balance of
electrolytes in the body as well as fluid, athletes or
people employed in outdoor work during warm
weather may need to replace the electrolytes lost in
sweat by taking capsules or drinking beverages
containing supplemental electrolytes.
With regard to the sense of thirst, it is not always
an accurate indication of the body’s need for water.
Researchers have found that many people do not feel
thirsty until they have already lost about 2 percent of
their total body weight through fluid losses. As a
result, most people will not replace enough fluid
during exercise or hot weather simply by drinking
water until they no longer feel thirsty. In addition,
the aging process, certain mental disorders, or drugs
may affect a person’s sense of thirst.
At the other extreme of water intake, a person
may drink excessive amounts of water due to misunderstandings about their need for extra fluid during
exercise. This condition is known as water intoxication
or hyperhydration. It leads to abnormally low levels of
sodium in the blood, a condition known as hyponatremia. Water intoxication may lead to swelling of the
brain, confusion, disorientation, and eventually coma
or death. Several marathon runners have died from
water intoxication since 2002, as have teenagers who
consumed large amounts of water after taking doses of
Ecstasy (MDMA), a so-called ‘‘club drug.’’ Other
persons at risk for water intoxication include people
with eating disorders and children with mental retardation. An important article published in the New
England Journal of Medicine in April 2005 reported
that as many as 13 percent of marathon runners developed hyponatremia during the course of a race as a
result of dr! inking too much water, usually 3 quarts or
more. Female athletes appear to be at greater risk of
water intoxication and hyponatremia than male
athletes.
GALE ENCYCLOPEDIA OF MEDICINE

The most common conditions leading to fluid and
electrolyte imbalance are as follows:


Exposure to extended periods of extremely hot
weather.



High levels of athletic activity, military training, or
outdoor work in such fields as construction, agriculture, forestry, fishing, and certain types of
manufacturing.



Extreme changes in diet.



Reduced fluid intake.



Medication side effects. Certain drugs, particularly
diuretics, beta-blockers, and vasodilators, may
increase the loss of electrolytes in urine and/or interfere with the body’s ability to regulate its temperature during exercise or in hot weather.



Severe illnesses characterized by high fever, recurrent
diarrhea, and/or frequent vomiting. Such illnesses
include cholera, viral gastroenteritis (‘‘stomach
flu’’), shigellosis, and amebic dysentery.



Severe burns covering more than 10 percent of the
body.



Surgical creation of a stoma or urinary diversion.
These operations sometimes lead to an increased
loss of body fluids while the patient’s body is adjusting to the changes in urination and excretion resulting from the surgery. In addition, some forms of
weight loss surgery intended to bypass parts of the
small intestine in which food absorption occurs have
a 70-percent rate of electrolyte imbalances as a complication of the operation.



Diseases affecting the kidneys. These include diabetes mellitus, diabetes insipidus, and syndrome of
inappropriate antidiuretic hormone secretion
(SIADH) as well as cancer or infections of the
kidneys.



In infants, premature birth.

through a tube or stoma directly into the small intestine) or parenteral nutrition (intravenous feeding that
bypasses the digestive tract).
The major categories of electrolyte supplements
are as follows:


Sports drinks. Sports drinks are beverages specially
formulated to contain appropriate amounts of electrolytes and carbohydrates as well as water to replace
the fluid and sodium lost through sweat during
athletic activities. These beverages are popular with
athletes at the college level, being used by about 3/4 of
the students on varsity teams at major universities.
According to the American College of Sports
Medicine as well as American and Canadian dietitians’ associations, sports drinks are effective in
supplying food energy for the muscles, maintaining
proper levels of blood sugar, maintaining the proper
functioning of the thirst mechanism, and lowering
the risk of dehydration or hyponatremia. Other
researchers have noted that the flavoring added to
sports drinks encourages athletes to drink more during periods of exercise and thus maintain proper
levels of hydration. Sports drinks can be purchased
in supermarkets as well as health food stores; they
include such well! -known beverages as Gatorade,
Lucozade, Red Devil, Powerade, and Red Alert.
Some of these popular supplements come in a semisolid form known as energy gels, some of which
contain caffeine or various herbal compounds as
well as carbohydrates and electrolytes.



Over-the-counter powders and tablets. Some athletes–particularly those who participate in such
sports as long-distance running or endurance
cycling—prefer capsules or concentrated powders
to maintain their electrolyte balance during exercise.
The powders are mixed with 12 or 16 ounces of cold
water prior to drinking, while the capsules can be
taken before, during, and after exercise. Most contain flavorings to mask the naturally salty or bitter
taste of the electrolytes themselves. Common brand
names include eForce, NutriBiotic, and Endurolytes;
prices range from $11 for 100 capsules to $35 for a
30-serving jar of powder. These products are
regarded by the Food and Drug Administration
(FDA) as dietary supplements.



Over-the-counter electrolyte replenishers for children. As has been mentioned earlier, infants and
young children are more vulnerable to dehydration
than adults, particularly from severe gastroenteritis
or diarrhea. A child may become dehydrated in less
than a day from recurrent vomiting or episodes of
diarrhea. Some doctors recommend that parents

Description
The various electrolyte supplements used in the
United States and Canada as of 2005 are intended to
prevent or treat electrolyte imbalances in very different situations or groups of patients. They range from
sports drinks and other supplements used by amateur
or professional athletes to prevent muscle cramps and
improve athletic performance, to liquids used at home
to prevent dehydration in children with diarrhea, to
injections administered as part of enteral (feeding
GALE ENCYCLOPEDIA OF MEDICINE

1279

Electrolyte supplements

Conditions associated with fluid and electrolyte
imbalance

Electrolyte supplements

keep oral rehydration fluids containing mixtures of
carbohydrates and electrolytes specially formulated
for children in the medicine chest at home in case the
child becomes dehydrated from a stomach virus or
similar illness. Common brand names for these products, which are regulated by the FDA as ‘‘medical
foods,’’ include Pedialyte, Infalyte, Naturalyte, and
Rehydralyte. Most come in a powdered form to be
mixed with water as well as liquid forms; Pedialyte is
also available as fruit-flavored freezer pops. Typical
prices range from $6 for a box of 16 freezer pops to
$34 for a quart of oral electrolyte solution.




Oral rehydration formulae for children and adults.
Oral rehydration salts, which are also known as
ORS, have been a staple of treatment for cholera
and other diseases accompanied by severe diarrhea
in developing countries for almost half a century.
First researched in the 1940s, oral rehydration salts
were adopted by the World Health Organization
(WHO) in 1978 in order to reduce the risk of death
from dehydration caused by cholera-related diarrhea. Since the introduction of ORS, the number of
children around the world who die from acute
diarrhea has been reduced from 5 million per year
to 1.3 million. Reformulated by WHO in 2002, the
ORS salts come in packets to be kept in the home and
mixed with water as soon as a child (or adult) falls ill.
The new formula is a low-glucose and low-sodium
mixture. If the WHO packets are unavailable, a
comparable form of oral rehydration solution can
be made by adding 8 tsp of table sugar, 1/2 tsp of
salt, 1/2 tsp of baking soda (bicarbona! te of soda),
and 1/3 tsp of potassium chloride to a liter (1.05
quarts) of water. In an emergency, a solution prepared from 1 tbsp of sugar and 1/2 tsp of salt added to
1 liter of water can be used to treat diarrhea.
Multiple electrolyte injections. Various mixtures of
electrolytes are available by prescription in injectable
form to be added to enteral or parenteral nutrition
formulae. These forms of feeding are used in patients
who require supplementation or complete replacement
of feeding by mouth, including patients with various
intestinal disorders, AIDS, or severe burns. Basic solutions for total parenteral nutrition, or TPN, contain the
electrolytes sodium, potassium, chloride, phosphate,
and magnesium, although the exact proportion of
electrolytes can be tailored to an individual patient’s
needs. Some injectable formulae contain dextrose, a
sugar, and acetate or lactate as well as the five major
electrolytes. Common brand names include Hyperlite,
TPN Electrolytes, Lypholyte, Nutrilyte, Plasma-Lyte
148, and others. Some patients are taught to use these
injectable formulae at home.

1280

Recommended dosage
Recommended dosages for electrolyte supplements are as follows:


Sports drinks. Since sports drinks and energy gels are
not medications in the strict sense, the amount
consumed will vary not only from person to person
but also in a given individual from day to day
depending on weather conditions, level of athletic
conditioning, length of activity, and other factors.
To lower the risk of dehydration in adults in hot
weather, the American College of Sports Medicine
recommends taking 20 ounces of a sports drink 2–3
hours before exercising; another 10 ounces 20 minutes before exercising; 10 ounces every 10–20 minutes
during exercise; and 20 ounces per pound of weight
lost during exercise after the activity is over. A group
of researchers at Texas A & M University suggests
that athletes competing in endurance events should
drink about 500 mL (1 pint) of a sports drink containing 4–8 percent of carbohydrates and electrolytes
1–2 hours before an event. For events lasting longer
than an hour, they should drink be! tween 600 and
1200 mL (1.25 to 2.5 pints) per hour of a sports drink
containing carbohydrate plus 0.5–0.7 grams of
sodium per quart.



Over-the-counter powders and tablets. The usual
recommended dose of powdered electrolytes is one
scoopful (or prepackaged envelope) of powder dissolved in 12–16 ounces of water before exercising.
Capsules may be taken as follows: 1–3 capsules
30–60 minutes before exercising; 1–6 capsules per
hour during the workout; and 1–3 capsules after
exercising.



Over-the-counter electrolyte replenishers for children.
Dosages for Pedialyte and similar oral rehydration
solutions for children are usually based on the child’s
age and weight. The child’s doctor should determine
the quantity to be given if the child is younger than
12 months of age. Children between the ages of 1 and
2 years are usually given 34 mL of electrolyte solution
per pound of body weight during the first eight hours
of treatment and 75 mL per pound of body weight
during the next 16 hours, although the doctor may
adjust the dose if the child is very thirsty. Children
between the ages of 2 and 10 are given 23 mL of
electrolyte solution per pound of body weight for the
first four to six hours of treatment, followed by 45 mL
per pound taken over the next 18–24 hours. Freezer
pops may be given to children older than 1 year as
often as the child desires.



Oral rehydration formulae. The WHO form of oral
rehydration liquid is made by adding the full
GALE ENCYCLOPEDIA OF MEDICINE



Multiple electrolyte injections. Basic TPN solutions
are usually made up in liter batches and adjusted to
each individual patient’s needs. The standard adult
dosage is 2 liters per day, usually administered by
drip through a needle or catheter placed in the
patient’s vein for a 10–12-hour period once a day or
5 days per week. The patient may be given several
units of premixed TPN fluid to store at home in the
refrigerator or freezer. Each dose should be taken
from the refrigerator 4–6 hours prior to use to
allow it to warm to room temperature. TPN solution
stored in a freezer should be moved to a refrigerator
24 hours before use.

Precautions


Sports drinks. Sports drinks should not be given to
rehydrate children with vomiting or diarrhea, as they
do not contain the proper balance of carbohydrates
and electrolytes needed by children’s bodies.



Over-the-counter powders and tablets. These products should always be taken with adequate amounts
of water and kept out of the reach of children.



Over-the-counter electrolyte replenishers for children. These preparations should be stored out of
the reach of children and away from heat and direct
sunlight. In addition, they should not be given to
patients with intestinal blockage.





Oral rehydration formulae. WHO oral rehydration
salts and packets of similar formulae should not be
stored in damp places, as moisture can cause the contents to lose their effectiveness. These products should
also be kept away from heat or direct sunlight.
Unused oral rehydration solution should be discarded
at the end of each day. As with electrolyte replenishers
for children, oral rehydration formulae should not be
given to patients with intestinal blockage.
Multiple electrolyte injections. Patients using multiple electrolyte injections as part of total parenteral
nutrition should have their blood and urine checked
at regular intervals while they are receiving these
medicines. They should also be taught to recognize
the signs of infection at the injection site (pain, swelling, redness, or a cold sensation). In addition, these

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anion—An ion carrying a negative charge owing to
a surplus of electrons. Anions in the body include
bicarbonate, chloride, phosphate, sulfate, certain
organic acids, and certain protein compounds.
Cation—An ion carrying a positive charge due to a
loss of electrons. Cations in the body include
sodium, potassium, magnesium, and calcium ions.
Cholera—A severe bacterial infection of the small
intestine characterized by profuse diarrhea and eventual dehydration. Cholera is still a frequent cause
of death among children in developing countries.
Electron—An elementary particle carrying a negative charge. Electrons may exist either independently
or as components of an atom outside its nucleus.
Enteral nutrition—Nourishment given through a
tube or stoma directly into the small intestine,
thus bypassing the upper digestive tract.
Hyponatremia—Insufficient sodium in the blood.
Interstitial spaces—Spaces within body tissues that
are outside the blood vessels. Interstitial spaces are
also known as interstitial compartments.
Ion—An atom or group of atoms that acquires an
electrical charge by the gain or loss of electrons.
Metabolism—The sum of an organism’s physical
and chemical processes that produce and maintain
living tissue, and make energy available to the
organism. Insulin resistance is a disorder of
metabolism.
Parenteral nutrition—Nutrition supplied intravenously, thus bypassing the patient’s digestive tract
entirely.
Stoma—A surgical opening made in the abdominal
wall to allow waste products to pass directly to the
outside.
Water intoxication—A potentially life-threatening
condition caused by drinking too much water,
which leads to hyponatremia and may result in
seizures, coma, and death.

patients should not use sports drinks, other electrolyte supplements, or over-the-counter medications
(including herbal preparations) without consulting
their doctor. The injections should not be used if
the fluid looks cloudy, has solid particles floating in
it, or has separated. The injections should be stored
away from sunlight and moisture. In addition,
patients receiving multiple electrolyte injections
1281

Electrolyte supplements

contents of one packet of powdered oral rehydration
salts to a quart of drinking water. The solution
should not be boiled. A fresh quart of solution
should be mixed each day. Infants and young children should be given the solution in small amounts
by spoon as often as possible. Adults and teenagers
should take the WHO formula according to the
doctor’s directions.

Electrolyte supplements

should not stop them suddenly without telling their
doctor, as the dosage may need to be reduced slowly
before the TPN is discontinued.



Oral rehydration formulae for adults. No interactions with other medications have been reported;
however, the doctor should be informed of all other
medications that the patient is taking in case a dosage
adjustment may be necessary.



Multiple electrolyte injections. Sports drinks and
other electrolyte supplements may raise total blood
electrolyte levels in patients receiving these
injections.

Side effects


Sports drinks. Some persons do not like the salty
taste of many sports drinks. They may wish to consider products containing glycine, which is an amino
acid that neutralizes the salty taste of the electrolytes
themselves. A more serious side effect of sports
drinks, however, is tooth decay. An article published
by researchers at the University of Maryland Dental
School in 2005 showed that sports drinks erode tooth
enamel at a rate three to 11 times faster than colabased soft drinks.



Over-the-counter powders and tablets. No side
effects have been reported for these products.



Over-the-counter electrolyte replenishers for
children. Side effects may include allergic reactions,
including hives, swelling of the face or hands, trouble breathing, tingling in the mouth or throat.
Other side effects may include signs of too much
sodium in the body, such as dizziness, seizures,
muscle twitching, or restlessness. The doctor
should be notified at once if any of these side effects
occur. A less serious side effect that occurs in some
children is mild vomiting.



Oral rehydration formulae. May produce the same
side effects as electrolyte replenishers for children.



Multiple electrolyte injections. Minor side effects
may include increased frequency of urination, dry
mouth, increased thirst, or drowsiness. Serious side
effects include rapid weight gain, yellowing of the
skin or eyes, fruity odor on the breath, numbness or
tingling in the hands or feet, uneven heartbeat, shortness of breath, confusion, or weakness with muscle
twitching. Patients should notify their doctor at once
if they notice any of these side effects.

Interactions


Sports drinks. Sports drinks may raise blood electrolyte levels in patients receiving total parenteral
nutrition.



Over-the-counter powders and tablets. No interactions have been reported.



Over-the-counter electrolyte replenishers for children. Children receiving premixed forms of these
preparations should not eat food with added salt or
drink fruit juices until the diarrhea has stopped.

1282

Resources
BOOKS

‘‘Childhood Infections: Acute Infectious Gastroenteritis.’’
Section 19, Chapter 265 in The Merck Manual of
Diagnosis and Therapy, edited by Mark H. Beers, MD,
and Robert Berkow, MD. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
‘‘Fluid and Electrolyte Disorders in Infants and Children.’’
Section 19, Chapter 259 in The Merck Manual of
Diagnosis and Therapy, edited by Mark H. Beers, MD,
and Robert Berkow, MD. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
‘‘Nutritional Support.’’ Section 1, Chapter 1 in The Merck
Manual of Diagnosis and Therapy, edited by Mark H.
Beers, MD, and Robert Berkow, MD. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
‘‘Water, Electrolyte, Mineral, and Acid-Base Metabolism.’’
Section 2, Chapter 12 in The Merck Manual of
Diagnosis and Therapy, edited by Mark H. Beers, MD,
and Robert Berkow, MD. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
PERIODICALS

Almond, Christopher S. D., MD, MPH, Andrew Y. Shin,
MD, Elizabeth B. Fortescue, MD, et al.
‘‘Hyponatremia among Runners in the Boston
Marathon.’’ New England Journal of Medicine 352
(April 14, 2005): 1550–1556.
Bovill, M. E., W. J. Tharion, and H. R. Lieberman.
‘‘Nutrition Knowledge and Supplement Use among
Elite U. S. Army Soldiers.’’ Military Medicine 168
(December 2003): 997–1000.
Comeau, Matthew J., PhD. ‘‘A Hot Issue for Summer
Exercisers.’’ ACSM Fit Society Page (Summer 2001): 4.
Froiland, K., W. Koszewski, J. Hingst, and L. Kopecky.
‘‘Nutritional Supplement Use among College Athletes
and Their Sources of Information.’’ International
Journal of Sport Nutrition and Exercise Metabolism 14
(February 2004): 104–120.
‘‘Position of Dietitians of Canada, the American Dietetic
Association, and the American College of Sports
Medicine: Nutrition and Athletic Performance.’’
Canadian Journal of Dietetic Practice and Research 61
(Winter 2000): 176–192.
Rao, M. C. ‘‘Oral Rehydration Therapy: New Explanations
for an Old Remedy.’’ Annual Review of Physiology 66
(2004): 385–417.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American College of Sports Medicine (ACSM). 401 West
Michigan Street, Indianapolis, IN 46202-3233. (317)
637-9200. Fax: (317) 634-7817. <http://
www.acsm.org>.
American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814. (301)
657-3000. <www.ashp.org>.
Rehydration Project. P. O. Box 1, Samara, 5235, Costa Rica.
+506 656-0504. Fax: +1 603 849-5656. <http://
rehydrate.org>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888)
INFO-FDA. <www.fda.gov>.
OTHER

Goodall, Roger M. ‘‘Oral Rehydration Therapy: How It
Works.’’. <http://rehydrate.org/ors/
ort_how_it_works.htm>.
World Health Organization (WHO) Media Centre press
release, 8 May 2002. ‘‘New Formula for Oral
Rehydration Salts Will Save Millions of Lives.’’
<http://www.who.int/mediacentre/news/releases/
release35/en>.

throughout the body. Electrolytes with a positive
charge include sodium, potassium, calcium, and
magnesium; the negative ions are chloride, bicarbonate, and phosphate. The concentrations of these ions
in the bloodstream remain fairly constant throughout
the day in a healthy person. Changes in the concentration of one or more of these ions can occur during
various acute and chronic disease states and can lead
to serious consequences.

Purpose
Tests that measure the concentration of electrolytes
are useful in the emergency room and to obtain clues for
the diagnosis of specific diseases. Electrolyte tests are
used for diagnosing dietary deficiencies, excess loss of
nutrients due to urination, vomiting, and diarrhea, or
abnormal shifts in the location of an electrolyte within
the body. When an abnormal electrolyte value is
detected, the physician may either act to immediately
correct the imbalance directly (in the case of an emergency) or run further tests to determine the underlying
cause of the abnormal electrolyte value. Electrolyte disturbances can occur with malfunctioning of the kidney
(renal failure), infections that produce severe and
continual diarrhea or vomiting, drugs that cause loss of
electrolytes in the urine (diuretics), poisoning due to accidental consumption of electrolytes, or diseases involving
hormones that regulate electrolyte concentrations.

Precautions
Electrolyte tests are performed from routine
blood tests. The techniques are simple, automated,
and fairly uniform throughout the United States.
During the preparation of blood plasma or serum,
health workers must take care not to break the red
blood cells, especially when testing for serum potassium. Because the concentration of potassium within
red blood cells is much higher than in the surrounding
plasma or serum, broken cells would cause falsely
elevated potassium levels.

Rebecca J. Frey, PhD

Description

I Electrolyte tests
Definition
Electrolytes are positively and negatively charged
molecules, called ions, that are found within cells,
between cells, in the bloodstream, and in other fluids
GALE ENCYCLOPEDIA OF MEDICINE

Electrolyte tests are typically conducted on blood
plasma or serum, urine, and diarrheal fluids.
Electrolytes can be classified in at least five different
ways. One way is that some electrolytes tend to exist
mostly inside cells, or are intracellular, while others
tend to be outside cells, or are extracellular.
Potassium, phosphate, and magnesium occur at
much greater levels inside the cell than outside, while
sodium and chloride occur at much greater levels
1283

Electrolyte tests

Rice, Henry, MD. ‘‘Fluid Therapy for the Pediatric Surgical
Patient.’’ eMedicine, 17 September 2004. <http://
www.emedicine.com/ped/topic2954>.
Sawka, Michael N., and Scott J. Montain. ‘‘Fluid and
Electrolyte Supplementation for Exercise Heat Stress.’’
American Journal of Clinical Nutrition 72 (August
2000): 564S–572S.
von Duvillard, S. P., W. A. Braun, M. Markofski, et al.
‘‘Fluids and Hydration in Prolonged Endurance
Performance.’’ Nutrition 20 (July-August 2004):
651–656.
von Frauenhofer, J. A., and M. M. Rogers. ‘‘Effects of
Sports Drinks and Other Beverages on Dental
Enamel.’’ General Dentistry 53 (January-February
2005): 28–31.
Wexler, Randell K., MD. ‘‘Evaluation and Treatment of
Heat-Related Illnesses.’’ American Family Physician 65
(June 1, 2002): 2307–2320.

Electrolyte tests

extracellularly. A second classification distinguishes
those electrolytes that participate directly in the transmission of nerve impulses and those that do not.
Sodium, potassium, and calcium are the important
electrolytes involved in nerve impulses, and disorders
affecting them are most closely associated with neurological disorders. A third classification focuses on
electrolytes that are able to form a tight union, or
complex, with one another. Calcium and phosphate
have the greatest tendency to form complexes with
each other. Disorders that cause an increase in either
plasma calcium or phosphate can result in the deposit
of calcium-phosphate crystals in the soft tissues of the
body. A fourth classification concerns those electrolytes that influence the acidity or alkalinity of the
bloodstream, also known as the pH. The pH of the
bloodstream is normally in the range of 7.35–7.45. A
decrease below this range is called acidosis, while a pH
above this range is called alkalosis. The electrolytes
most closely associated with the pH of the bloodstream are bicarbonate, chloride, and phosphate.

referred to as bound calcium. The normal range of free
calcium is 4.8–5.2 mg/dL. The normal concentration
of serum magnesium is in the range of 2.0–3.0 mg/dL.
The normal concentration range of chloride is
350–375 mg/dL or 98–106 mM. The normal level of
phosphate, as expressed as the concentration of phosphorus, is 2.0–4.3 mg/dL. Bicarbonate is an electrolyte
that is freely and spontaneously interconvertable with
carbonic acid and carbon dioxide. The normal concentration of carbonic acid (H2CO3) is about 1.35
mM. The normal concentration of bicarbonate
(HCO3–) is about 27 mM. The concentration of
total carbon dioxide is the sum of carbonic acid
and bicarbonate; this sum is normally in the range of
26–28 mM. The ratio of bicarbonate/carbonic acid is
more significant than the actual concentrations of
these two forms of carbon dioxide. Its normal value
is 27/1.35 (equivalent to 20/1).

Abnormal results
Positively charged electrolytes

Preparation
All electrolyte tests can be performed on plasma
or serum. Plasma is prepared by withdrawing a blood
sample and placing it in a test tube containing a chemical that prevents blood from clotting (an anticoagulant). Serum is prepared by withdrawing a blood
sample, placing it in a test tube, and allowing it to clot.
The blood spontaneously clots within a minute of
withdrawing the blood from a vein. The serum or
plasma is then rapidly spun with a centrifuge in order
to remove the blood cells or clot.

Normal results
Electrolyte concentrations are similar whether
measured in serum or plasma. Values can be
expressed in terms of weight per unit volume (mg/
deciliter; mg/dL) or in the number of molecules in a
volume, or molarity (moles or millimoles/liter; M or
mM). The range of normal values sometimes varies
slightly between different age groups, for males
and females, and between different analytical
laboratories.
The normal level of serum sodium is in the range
of 136–145 mM. The normal levels of serum potassium are 3.5–5.0 mM. Note that sodium occurs at
a much higher concentration than potassium. The
normal concentration of total serum calcium
(bound calcium plus free calcium) is in the range of
8.8–10.4 mg/dL. About 40% of the total calcium in the
plasma is loosely bound to proteins; this calcium is
1284

High serum sodium levels (hypernatremia) occur
at sodium concentrations over 145 mM, with severe
hypernatremia over 152 mM. Hypernatremia is
usually caused by diseases that cause excessive urination. In these cases, water is lost, but sodium is still
retained in the body. The symptoms include confusion
and can lead to convulsions and coma. Low serum
sodium levels (hyponatremia) are below 130 mM,
with severe hyponatremia at or below 125 mM.
Hyponatremia often occurs with severe diarrhea,
with losses of both water and sodium, but with sodium
loss exceeding water loss. Hyponatremia provokes
clinical problems only if serum sodium falls below
125 mM, especially if this has occurred rapidly. The
symptoms can be as mild as tiredness but may lead to
convulsions and coma.
High serum potassium (hyperkalemia) occurs at
potassium levels above 5.0 mM; it is considered severe
over 8.0 mM. Hyperkalemia is relatively uncommon,
but sometimes occurs in patients with kidney failure
who take potassium supplements. Hyperkalemia can
result in abnormal beating of the heart (cardiac
arrhythmias). Low serum potassium (hypokalemia)
occurs when serum potassium falls below 3.0 mM. It
can result from low dietary potassium, as during starvation or in patients with anorexia nervosa; from
excessive losses via the kidneys, as caused by diuretic
drugs; or by diseases of the adrenal or pituitary glands.
Mild hypokalemia causes muscle weakness, while
severe hypokalemia can cause paralysis, the inability
to breathe, and cardiac arrhythmias.
GALE ENCYCLOPEDIA OF MEDICINE

Hypermagnesemia occurs at serum magnesium
levels over 25 mM (60 mg/dL). Hypermagnesemia is
rare but can occur with the excessive consumption of
magnesium salts. Hypomagnesemia occurs when
serum magnesium levels fall below 0.8 mM, and can
result from poor nutrition. Chronic alcoholism is the
most common cause of hypomagnesemia, in part
because of poor diet. Magnesium levels below 0.5 mM
(1.2 mg/dL) cause serum calcium levels to decline.
Some of the symptoms of hypomagnesemia, including
twitching and convulsions, actually result from the
concurrent hypocalcemia. Hypomagnesemia can also
result in hypokalemia and thereby cause cardiac
arrhythmias.
Negatively charged electrolytes
Serum chloride levels sometimes increase to
abnormal levels as an undesirable side effect of medical
treatment with sodium chloride or ammonium chloride. The toxicity of chloride results not from the chloride itself, but from the fact that the chloride occurs as
the acid, hydrogen chloride (more commonly known
as hydrochloric acid, or HCl). An overdose of chloride
may cause the accumulation of hydrochloric acid in
the bloodstream, with consequent acidosis. Renal
tubular acidosis, one of many kidney diseases, involves
the failure to release acid into the urine. The acidosis
produces weakness, headache, nausea, and cardiac
arrest. Low plasma chloride leads to the opposite
situation: a decline in the acid content of the bloodstream. This is known as alkalization of the bloodstream, or alkalosis. Hydrochloric acid, originally
from extracellular fluids, can be lost by vomiting. At
its most severe, alkalosis results in paralysis (tetany).
GALE ENCYCLOPEDIA OF MEDICINE

Hyperphosphatemia occurs at serum phosphate
levels above 5 mg/dL. It can result from the failure of
the kidneys to excrete phosphate into the urine, causing phosphate to accumulate in the bloodstream.
Hyperphosphatemia can also be caused by the
impaired action of parathyroid hormone and by phosphate poisoning. Severe hyperphosphatemia can cause
paralysis, convulsions, and cardiac arrest. These
symptoms result because the phosphate, occurring in
elevated levels, complexes with free serum calcium,
resulting in hypocalcemia. Tests for heart function
(an electrocardiogram) and parathyroid hormone
levels are used in the diagnosis of hyperphosphatemia.
Hypophosphatemia occurs if serum phosphorus falls
to 2.0 mg/dL or lower. It often results from a shift of
inorganic phosphate from the bloodstream to various
organs and tissues. This shift can be caused by a rise in
pH (alkalization) of the bloodstream, which can occur
during hyperventilation, a reaction in various disease
states. A shift in phosphate to intracellular tissues may
draw calcium away from the bloodstream via the formation of insoluble calcium phosphate crystals within
cells, with consequent hypocalcemia. Thus, tests for
abnormalities in phosphate metabolism also involve
tests for serum calcium.
Bicarbonate metabolism involves several compounds. When dietary starches, sugars, and fats are
broken down for energy production, carbon dioxide is
created. Much of this carbon dioxide (CO2) spontaneously converts to carbonic acid (H2CO3), and
some of the carbonic acid spontaneously converts
to bicarbonate (HCO3–) plus a hydrogen ion (H–).
Eventually, almost every molecule of carbon dioxide
produced in the body, whether in the form of carbon
dioxide, carbonic acid, or bicarbonate, must convert
back to carbon dioxide in order to leave via the lungs
during normal breathing.
If one holds one’s breath, carbon dioxide cannot
escape from the lungs, but continues to be generated
within the body. This results in an increase in production of carbonic acid. A portion of the carbonic acid
breaks apart (dissociates), causing an increase in
hydrogen ions in the plasma, with a resulting acidosis.
Tests for serum bicarbonate levels are accompanied by
tests for acidosis (pH test). Conversely, when one
breathes too rapidly (hyperventilation), the carbon
dioxide is drawn off from the bloodstream and
expelled in the breath at an increased rate. This results
in an increase in the rate of combination of bicarbonate with hydrogen ions, resulting in alkalosis.
Acidosis and alkalosis can be produced by means
other than by altering the rate of breathing. The carbonic acid and bicarbonate in the bloodstream
1285

Electrolyte tests

High levels of calcium ions (hypercalcemia) occur
at free calcium ion concentrations over 5.2 mg/dL
or total serum calcium above 10.4 mg/dL.
Hypercalcemia usually occurs when the body dissolves
bone at an abnormally fast rate, increasing both serum
calcium and serum phosphate. Sudden hypercalcemia
can cause vomiting and coma, while prolonged and
moderate hypercalcemia results in the deposit of calcium phosphate crystals in the kidneys and eye.
Hypocalcemia occurs when serum free calcium ions
fall below 4.4 mg/dL, or when total serum calcium
falls below 8.8 mg/dL. Hypocalcemia can result from
hypoparathyroidism (low parathyroid hormone), from
failure to produce 1,25-dihydroxyvitamin D, from low
levels of plasma magnesium, and from phosphate poisoning (the phosphate enters the bloodstream and
forms a complex with the free serum calcium).
Hypocalcemia can cause depression and muscle
spasms.

Electromyography

minimize (or buffer) any trend to acidosis or alkalosis.
Tests for bicarbonate are generally accompanied by
tests for blood pH and possibly tests for kidney malfunction, abnormal hormone function, or gastrointestinal disorders.



mitochondrial myopathies



metabolic myopathies



myotonias



peripheral neuropathies

Resources



radiculopathies

PERIODICALS



nerve lesions



amyotrophic lateral sclerosis



polio



spinal muscular atrophy



Guillain-Barré syndrome



ataxias



myasthenias

Fried, L. F., and P. M. Palevsky. ‘‘Hyponatremia and
hypernatremia.’’ Medical Clinics of North America 81
(1997): 585-609.

Tom Brody, PhD

I Electromyography
Definition
Electromyography (EMG) is an electrical recording of muscle activity that aids in the diagnosis of
neuromuscular disease.

Purpose
Muscles are stimulated by signals from nerve cells
called motor neurons. This stimulation causes electrical activity in the muscle, which in turn causes contraction. This electrical activity is detected by a needle
electrode inserted into the muscle and connected to a
recording device. Together, the electrode and recorder
are called an electromyography machine. EMG can
determine whether a particular muscle is responding
appropriately to stimulation, and whether a muscle
remains inactive when not stimulated.
EMG is performed most often to help diagnose
different diseases causing weakness. Although EMG is
a test of the motor system, it may help identify
abnormalities of nerves or spinal nerve roots that
may be associated with pain or numbness. Other symptoms for which EMG may be useful include numbness,
atrophy, stiffness, fasciculation, cramp, deformity,
and spasticity. EMG results can help determine
whether symptoms are due to a muscle disease or a
neurological disorder, and, when combined with clinical findings, usually allow a confident diagnosis.
EMG can help diagnose many muscle and nerve
disorders, including:


muscular dystrophy



congenital myopathies

1286

Precautions
No special precautions are needed for this test.
Patients with a history of bleeding disorder should
consult with their treating physician before the test.
If a muscle biopsy is planned as part of the diagnostic
work-up, EMG should not be performed at the same
site, as it may effect the microscopic appearance of the
muscle.

Description
During an EMG test, a fine needle is inserted into
the muscle to be tested. This may cause some discomfort, similar to that of an injection. Recordings are
made while the muscle is at rest, and then during the
contraction. The person performing the test may move
the limb being tested, and direct the patient to move it
with various levels of force. The needle may be repositioned in the same muscle for further recording. Other
muscles may be tested as well. A typical session lasts
from 30–60 minutes.
A slightly different test, the nerve conduction
velocity test, is often performed at the same time
with the same equipment. In this test, stimulating
and recording electrodes are used, and small electrical shocks are applied to measure the ability of the
nerve to conduct electrical signals. This test may
cause mild tingling and discomfort similar to a mild
shock from static electricity. Evoked potentials
may also be performed for additional diagnostic
information. Nerve conduction velocity and evoked
potential testing are especially helpful when pain or
sensory complaints are more prominent than
weakness.
GALE ENCYCLOPEDIA OF MEDICINE

Motor neurons—Nerve cells that transmit signals
from the brain or spinal cord to the muscles.
Motor unit action potentials—Spikes of electrical
activity recorded during an EMG that reflect the
number of motor units (motor neurons and the
muscle fibers they transmit signals to) activated
when the patient voluntarily contracts a muscle.

Electrical activity at rest is abnormal; the particular pattern of firing may indicate denervation (for
example, a nerve lesion, radiculopathy, or lower
motor neuron degeneration), myotonia, or inflammatory myopathy.
Decreases in the amplitude and duration of spikes
are associated with muscle diseases, which also show
faster recruitment of other muscle fibers to compensate for weakness. Recruitment is reduced in nerve
disorders.
Resources

Preparation
No special preparation is needed. The doctor
supervising and interpreting the test should be given
information about the symptoms, medical conditions,
suspected diagnosis, neuroimaging studies, and other
test results.

OTHER

Falck, B., E. Stalberg, and L. Korpinen. The Expert
Electromyographer. <http://www.tut.fi/korpinen/
EMG.htm>.

Richard Robinson

Aftercare
Minor pain and bleeding may continue for several
hours after the test. The muscle may be tender for a
day or two.

I Electronic fetal monitoring
Definition

Risks
There are no significant risks to this test, other
than those associated with any needle insertion (pain,
bleeding, bruising, or infection).

Normal results
There should be some brief EMG activity during
needle insertion. This activity may be increased in
diseases of the nerve and decreased in long-standing
muscle disorders where muscle tissue is replaced by
fibrous tissue or fat. Muscle tissue normally shows
no EMG activity when at rest or when moved passively by the examiner. When the patient actively
contracts the muscle, spikes (motor unit action
potentials) should appear on the recording screen,
reflecting the electrical activity within. As the muscle
is contracted more forcefully, more groups of muscle
fibers are recruited or activated, causing more EMG
activity.

Abnormal results
The interpretation of EMG results is not a simple
matter, requiring analysis of the onset, duration,
amplitude, and other characteristics of the spike
patterns.
GALE ENCYCLOPEDIA OF MEDICINE

Electronic fetal monitoring (EFM) is a method for
examining the condition of a baby in the uterus by
noting any unusual changes in its heart rate.
Electronic fetal monitoring is performed late in pregnancy or continuously during labor to ensure normal
delivery of a healthy baby. EFM can be utilized either
externally or internally in the womb.

Purpose
The heart rate of a fetus undergoes constant
adjustment as it responds to its environment and
other stimuli. The fetal monitor records an unborn
baby’s heart rate and graphs it on a piece of paper.
Electronic fetal monitoring is usually advised for highrisk pregnancies, when the baby is in danger of distress. Specific reasons for EFM include: babies in a
breech position, premature labor, and induced labor,
among others.
When electronic fetal monitoring was originally
introduced in the 1960s and 1970s, the hope was that it
would help physicians diagnose fetal hypoxia, or lack
of oxygen, in time to prevent damage to the baby. This
lack of oxygen, also known as perinatal asphyxia or
birth asphyxia, is an important cause of stillbirth and
newborn deaths. It occurs when there are less than
normal amounts of oxygen delivered to the body or
1287

Electronic fetal monitoring

KEY TERMS

Electronic fetal monitoring

an organ and there is build-up of carbon dioxide in the
body or tissue. A lack of blood flow to an organ can
cause asphyxia. Perinatal asphyxia can occur a long
time before birth, shortly before birth, during delivery,
or after birth. If the interruption to the supply of
oxygen is short, the baby may recover without any
damage. If the time is longer, there may be some injury
that is reversible. If the time period without oxygen is
very long, there may be permanent injury to one or
more organs of the body. It is important to detect any
signs of asphyxia as soon as possible. One of the signs
is an abnormal heart rate and rhythm in the unborn
baby, which can be detected by electronic fetal
monitoring.
The fetal monitor is a more intricate version of the
machine that a health care provider uses to listen to a
baby’s heartbeat. The monitor that is used during
prenatal visits just picks up the sound of the baby’s
heart beating. The fetal monitor also keeps a continuous paper record of the heart rate. In addition, the fetal
monitor can record uterine contractions on the lower
part of the paper strip. This helps the doctor or midwife
determine how a baby is handling the stress of contractions. The normal pattern is for the baby’s heartbeat to
drop slightly during a contraction and then go back to
normal after the contraction is over. EFM looks for any
changes from this normal pattern, particularly if there
is a drastic drop in the baby’s heart beat or if the heart
rate does not recover immediately after a contraction.

Umbilical cord
Pubic bone
Intrauterine
pressure catheter

Vagina

Electronic fetal monitoring (EFM) is performed late in pregnancy or continuously during labor to ensure normal delivery
of a healthy baby. EFM can be utilized either externally or
internally in the womb. The illustration above shows the
internal procedure, in which an electrode is attached directly
to the baby’s scalp to monitor the heart rate. Uterine contractions are recorded using an intrauterine pressure catheter
which is inserted through the cervix into the uterus.
(Illustration by the Electronic Illustrators Group.)

(late decelerations). If a baby is not receiving enough
oxygen to withstand the stress of labor and delivery is
many hours away, a cesarean section (C-section) may
be necessary.

Description

Because it is an indirect test, it is not perfect. When
an adult complains to a provider about not feeling
well, checking the heart rate is only one of many things
that the doctor will do. With an unborn baby, however, checking the heart rate is basically the only thing
that a doctor or midwife can do.

Using the external fetal monitor is simple and
painless. Two elastic belts are placed around the
mother’s abdomen. One belt holds a listening device
in place while the other belt holds the contraction
monitor. The nurse or midwife adjusts the belts to
get the best readings from each device.

Fetal monitoring can be helpful in a variety of
different situations. During pregnancy, fetal monitoring can be used as a part of antepartum testing. If the
practitioner feels that a baby may be at increased risk
of problems toward the end of pregnancy, a baby can
be checked every week or every other week with a nonstress test. In this test, changes in the baby’s heart rate
are measured along with the fetus’ own movements.
The heart rate of a healthy baby should go up whenever she or he moves.

Sometimes, it is difficult to hear the baby’s heartbeat with the external monitoring device. Other times,
the monitor may show subtle signs of a developing
problem. In either case, the doctor or midwife may
recommend that the external belt be replaced with an
internal monitor.

Fetal monitoring is used on and off during early
labor. As labor progresses, more monitoring is often
needed. Usually, as the time for delivery nears, the
monitor is left on continuously since the end of labor
tends to be the most stressful time for the baby.
A baby who is having trouble in labor will show
characteristic changes in heart rate after a contraction
1288

The internal monitor is an electronic wire that
rests directly on the baby’s head. The provider can
place it on the baby’s head during an internal exam.
The internal monitor can only be used when the cervix
is already open. This device provides a more accurate
record of the baby’s heart rate.

Preparation
There are no special preparations needed for fetal
monitoring.
GALE ENCYCLOPEDIA OF MEDICINE

External EFM poses no direct risks to the baby.
However, because of being connected to the
machine, the mother cannot walk around. This
inactivity may prolong labor and reduce oxygen
levels in the mother’s blood, both of which can be
detrimental to the unborn baby. Another problem is
that electronic fetal monitoring seems to be associated with an increase in caesarian deliveries.
There is a concern that EFM can give false alarms
of distress in the baby, and that this can lead to
unneeded caesarians. With internal monitoring,
there is a higher risk for infection. For these and
other reasons, the United States Preventive Services
Task Force states that there is some evidence that
using electronic fetal monitoring on low-risk women
in labor might not be indicated. Many physicians,
however, continue to use EFM routinely, and believe
it to be of value in both low-risk and high-risk labors.

Normal results
An unborn baby’s heart rate normally ranges
from 120–160 beats per minute (bpm). A baby who is
receiving enough oxygen through the placenta will
move around. The monitor strip will show the baby’s
heart rate rising briefly as he/she moves (just as an
adult’s heart rate rises when he/she moves).
The baby’s monitor strip is considered to be reactive
when the baby’s heart rate rises at least 20 bpm above the
baseline heart rate for at least 20 seconds. This must
occur at least twice in a 20-minute period. A reactive
heart rate tracing (also known as a reactive non-stress
test) is considered a sign of the baby’s well being.

Abnormal results
If the baby’s heart rate drops very low or rises very
high, this signals a serious problem. In either of these
cases it is obvious that the baby is in distress and must
be delivered soon. However, many babies who are
having problems do not give such clear signs.
During a contraction, the flow of oxygen (from
the mother) through the placenta (to the baby) is
temporarily stopped. It is as if the baby has to hold
its breath during each contraction. Both the placenta
and the baby are designed to withstand this condition.
Between contractions, the baby should be receiving
more than enough oxygen to do well during the
contraction.
The first sign that a baby is not getting enough
oxygen between contractions is often a drop in the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Breech presentation—Fetal position in which the
buttocks come first.
Cesarean section c-section—Delivery of a baby
through an incision in the mother’s abdomen
instead of through the vagina.
Hypoxia—An oxygen deficiency.

baby’s heart rate after the contraction (late deceleration). The baby’s heart rate recovers to a normal level
between contractions, only to drop again after the
next contraction. This is also a more subtle sign of
distress.
These babies will do fine if they are delivered in a
short period of time. Sometimes, these signs develop
long before delivery is expected. In that case, a
C-section may be necessary.
Resources
PERIODICALS

Kripke, Clarissa C. ‘‘Why Are We Using Electronic
FetalMonitoring?’’ American Family Physician May
1,1999.
Sweha, Amir, et al. ‘‘Interpretation of the Electronic
FetalHeart Rate During Labor’’ American Family
Physician May 1,1999.

Deanna M. Swartout-Corbeil, R.N.

study
I Electrophysiology
of the heart
Definition
An electrophysiology (EP) study of the heart is a
nonsurgical analysis of the electrical conduction
system (normal or abnormal) of the heart. The test
employs cardiac catheters and sophisticated computers to generate electrocardiogram (EKG) tracings
and electrical measurements with exquisite precision
from within the heart chambers.
The EP study can be performed solely for diagnostic purposes. It also is performed to pinpoint the
exact location of electrical signals (cardiac mapping)
in conjunction with a therapeutic procedure called
catheter ablation.
1289

Electrophysiology study of the heart

Risks

Electrophysiology study of the heart

The test is simple, not painful, and performed in a
special laboratory under controlled clinical circumstances by cardiologists and nurses who subspecialize
in electrophysiology.

Purpose
A cardiologist may recommend an EP study when
the standard EKG, Holter monitor, event recorder,
stress test, echocardiogram, or angiogram cannot provide enough information to evaluate an abnormal
heart rhythm, called an arrhythmia.
An EP study also may be beneficial in diagnosing
a suspected arrhythmia in a patient who shows symptoms of an arrhythmia but in whom it could not be
detected from other tests.
The purpose and great value of an EP study is
that it offers more detailed information to the doctor
about the electrical activity in the heart than the
aforementioned noninvasive tests because electrodes
are placed directly on heart tissue. This allows the
electrophysiologist to determine the specific location
of an arrhythmia and, oftentimes, correct it
during the same procedure. This corrective treatment is permanent and considered a cure, and, in
many cases, the patient may not need to take heart
medications.
EP studies may be helpful in assessing:


certain tachycardias or bradycardias of unknown
cause



patients who have been resuscitated after experiencing sudden cardiac death



various symptoms of unknown cause, such as chest
pain, shortness of breath, fatigue, or syncope (dizziness/fainting)



response to anti-arrhythmic therapy

Precautions
Pregnant patients should not undergo an EP
study because of exposure to radiation during the
study, which may be harmful to the growing baby.
Patients who have coronary artery disease may
need to have that treated before having an EP study.

Description
The rhythmic pumping action of the heart, which
is essentially a muscle, is the result of electrical
impulses traveling throughout the walls of the four
heart chambers. These impulses originate in the
1290

sinoatrial (SA) node, which are specialized cells
situated in the top right chamber of the heart: the
right atrium. Normally, the SA node, acting like a
spark plug, spontaneously generates the impulses,
which travel through specific pathways throughout
the atria to the atrioventricular (AV) node. The AV
node is a relay station, sending the impulses to more
specialized muscle fibers throughout the bottom
chambers of the heart: the ventricles. If these pathways become damaged or blocked or if extra (abnormal) pathways exist, the heart’s rhythm may be
altered (perhaps too slow, too fast, or irregular),
which can seriously affect the heart’s pumping
ability.
The patient is transported to the x-ray table in the
EP lab and connected to various monitors. Sterile
sheets are placed over him or her. A minimum of two
catheters are inserted into the right femoral (thigh)
vein in the groin area. Depending on the type of
arrhythmia, the number of catheters used in an EP
test and their route to the heart may vary. For certain
tachycardias, two more catheters may be inserted in
the left groin and one in the internal jugular (neck)
vein or in the subclavian (below the clavicle) vein. The
catheters are about 0.08 in (2 mm) in diameter, about
the size of a spaghetti noodle. The catheters used in
catheter ablation are slightly larger.
With the help of fluoroscopy (x rays on a television screen), all the catheters are guided to several
specific locations in the heart. Typically, four to 10
electrodes are located on the end of the catheters,
which have the ability to send electrical signals to
stimulate the heart (called pacing) and to receive electrical signals from the heart–but not at the same time
(just as a walkie-talkie cannot send and receive messages at the same time).
First, the electrodes are positioned to receive signals from inside the heart chambers. This allows the
doctor to measure how fast the electrical impulses
travel currently in the patient’s heart. These measurements are called the patient’s baseline measurements.
Next, the electrodes are positioned to pace: The EP
team actually tries to induce (sometimes in combination with various heart drugs) the arrhythmia that the
patient has previously experienced so the team can
observe it in a controlled environment, compare it to
the patient’s clinical or spontaneous arrhythmia, and
decide how to treat it.
Once the arrhythmia is induced and the team
determines it can be treated with catheter ablation,
cardiac mapping is performed to locate precisely the
origin and route of the abnormal pathway. When this
GALE ENCYCLOPEDIA OF MEDICINE

Electrophysiology study of the heart
An electrophysiologist nurse monitors a patient’s heart rhythm during an electrophysiology study for tachycardia. (Photograph
by Collette Placek. Reproduced by permission.)

is accomplished, the ablating electrode catheter is
positioned directly against the abnormal pathway,
and high radio-frequency energy is delivered through
the electrode to destroy (burn) the tissue in this area.

Preparation
The following preparations are made for an EP
study:


the patient may be advised to stop taking certain
medications, especially heart drugs, that may interfere with the test results.



blood tests usually are ordered the week before the test.



the patient undergoes conscious sedation (awake but
relaxed) during the test. This is accomplished quite
often with the anesthetic drugs VersedR (Roche
laboratories) and fentanyl.



a local anesthetic is injected at the site of catheter
insertion.

GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
The patient needs to rest flat in bed for several
hours after the procedure to allow healing at the catheter insertion sites.
The patient often returns home either the same
day of the test or the next day. Someone should drive
him or her home.
The doctor may prescribe drugs and/or insert an
AFCD to treat the arrhythmia and may do a possible
follow-up EP study.

Risks
The EP diagnostic study and catheter ablation
are low-risk procedures. There is a small risk of
bleeding and/or infection at the site of catheter insertion, but this occurs less than 1% of the time. Blood
clot formation occurs only two in 1,000 instances
and is minimized with blood thinner medications
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Elephantiasis

Normal results

KEY TERMS
Ablation—Remove or destroy, such as by burning
or cutting.
Angiogram—X ray of a blood vessel after special
x-ray dye has been injected into it.
Bradycardia—Slow heartbeat.
Cardiac catheter—Long, thin, flexible tube
that is threaded into the heart through a blood
vessel.
Cardiologist—Doctor who specializes in diagnosing and treating heart diseases.
Echocardiogram—Ultrasound image of the heart.
Electrocardiogram—Tracing of the electrical activity of the heart.
Electrode—Medium for conducting an electrical
current–in this case, platinum wires.
Electrophysiology—Study of how electrical signals
in the body relate to physiologic function.
Event recorder—A small machine, worn by a
patient usually for several days or weeks, that is
activated by the patient to record his or her EKG
when a symptom is detected.
Fibrillation—Rapid, random contraction (quivering).
Holter monitor—A small machine, worn by a
patient usually for 24 hours, that continuously
records the patient’s EKG during usual daily activity.
Stress test—Recording a patient’s EKG during
exercise.
Supraventricular tachycardia—A fast heart beat
that originates above the ventricles.
Tachycardia—Fast heartbeat.
Vascular—Pertaining to blood vessels.

The heart initiates and conducts electrical
impulses normally.

Abnormal results
Confirmation of arrhythmias, such as:


supraventricular tachycardias



ventricular arrhythmias



accessory (extra) pathways



bradycardias

Resources
ORGANIZATIONS

Cardiac Arrhythmia Research and Education Foundation
(C.A.R.E.). 2082 Michelson Dr. #301 Irvine, CA 92612
1-800-404-9500. <http://www.longqt.com>.
Medtronics Manufacturer of Therapeutic Devices. 710
Medtronic Parkway NE, Minneapolis, MN 554325604. (800) 328-2518. <http://www.medtronic.com>.
Midwest Heart Specialists. Physician Office Building, 3825
Highland Ave., Tower 2, Ste. 400, Downers Grove,
Illinois 60515. (630) 719-4799. <http://
www.midwestheart.com>.
United States Catheter Instruments (USCI). 129 Concord
Road Billerica, MA 01821. (800) 826-2273.

Collette L. Placek

Electroshock therapy see Electroconvulsive
therapy

I Elephantiasis
Definition

administered during the procedure. Vascular injuries
causing hemorrhage or thrombophlebitis are
possible but occur less than 0.7% of the time.
Cardiac perforations occur only in one or two per
1,000 instances. If the right internal jugular vein is
accessed, the small possibility of puncturing the lung
with the catheter exists, which, at worst, could cause
a collapsed lung.
Because ventricular tachycardia or fibrillation
(lethal arrhythmias) may be induced in the patient,
the EP lab personnel must be prepared to defibrillate
the patient as necessary.
1292

The word elephantiasis is a vivid and accurate
term for the syndrome it describes: the gross (visible)
enlargement of the arms, legs, or genitals to elephantoid size.

Description
True elephantiasis is the result of a parasitic infection caused by three specific kinds of round worms.
The long, threadlike worms block the body’s lymphatic system–a network of channels, lymph nodes, and
organs that helps maintain proper fluid levels in the
body by draining lymph from tissues into the bloodstream. This blockage causes fluids to collect in the
tissues, which can lead to great swelling, called
GALE ENCYCLOPEDIA OF MEDICINE

There are a few different causes of elephantiasis,
but the agents responsible for most of the elephantiasis in the world are filarial worms: white, slender
round worms found in most tropical and subtropical
places. They are transmitted by particular kinds (species) of mosquitoes, that is, bloodsucking insects.
Infection with these worms is called ‘‘lymphatic filariasis’’ and over a long period of time can cause
elephantiasis.
Lymphatic filariasis is a disease of underdeveloped regions found in South America, Central
Africa, Asia, the Pacific Islands, and the Caribbean.
It is a disease that has been present for centuries,
as ancient Persian and Indian writings clearly
described elephant-like swellings of the arms, legs,
and genitals. It is estimated that 120 million people
in the world have lymphatic filariasis. The disease
appears to be spreading, in spite of decades of research
in this area.
Other terms for elephantiasis are Barbados leg,
elephant leg, morbus herculeus, mal de Cayenne, and
myelolymphangioma.
Other situations that can lead to elephantiasis are:


a protozoan disease called leishmaniasis



a repeated streptococcal infection



the surgical removal of lymph nodes (usually to prevent the spread of cancer)



a hereditary birth defect

Causes and symptoms
Three kinds of round worms cause elephantiasis
filariasis: Wuchereria bancrofti, Brugia malayi, and
Brugia timori. Of these three, W. bancrofti makes up
about 90% of the cases. Man is the only known host of
W. bancrofti.
Culex, Aedes, and Anopheles mosquitoes are the
carriers of W. bancrofti. Anopheles and Mansonia mosquitoes are the carriers of B. malayi. In addition,
Anopheles mosquitoes are the carriers of B. timori.
Infected female mosquitoes take a blood meal
from a human, and in doing so, introduce larval
forms of the particular parasite they carry to the person. These larvae migrate toward a lymphatic channel,
then travel to various places within the lymphatic
system, usually positioning themselves in or near
GALE ENCYCLOPEDIA OF MEDICINE

lymph nodes throughout the body. During this time,
they mature into more developed larvae and eventually into adult worms. Depending upon the species
of round worm, this development can take a few
months or more than a year. The adult worms grow
to about 1 in (2.5 cm) to 4 in (10 cm) long.
The adult worms can live from about three to
eight years. Some have been known to live to 20
years, and in one case 40 years. The adult worms
begin reproducing numerous live embryos, called
microfilariae. The microfilariae travel to the bloodstream, where they can be ingested by a mosquito
when it takes a blood meal from the infected person.
If they are not ingested by a mosquito, the microfilariae die within about 12 months. If they are ingested by
a mosquito, they continue to mature. They are totally
dependent on their specific species of mosquito to
develop further. The cycle continues when the mosquito takes another blood meal.
Most of the symptoms an infected person
experiences are due to the blockage of the lymphatic
system by the adult worms and due to the substances (excretions and secretions) produced by the
worms.
The body’s allergic reactions may include
repeated episodes of fever, shaking chills, sweating,
headaches, vomiting, and pain. Enlarged lymph
nodes, swelling of the affected area, skin ulcers, bone
and joint pain, tiredness, and red streaks along the arm
or leg also may occur. Abscesses can form in lymph
nodes or in the lymphatic vessels. They may appear at
the surface of the skin as well.
Long-term infection with lymphatic filariasis
can lead to lymphedema, hydrocele (a buildup of
fluid in any saclike cavity or duct) in the scrotum,
and elephantiasis of the legs, scrotum, arms, penis,
breasts, and vulvae. The most common site of elephantiasis is the leg. It typically begins in the ankle
and progresses to the foot and leg. At first the
swollen leg may feel soft to the touch but eventually
becomes hard and thick. The skin may appear darkened or warty and may even crack, allowing bacteria to infect the leg and complicate the disease.
The microfilariae usually don’t cause injury. In
some instances, they cause ‘‘eosinophilia,’’ an
increased number of eosinophils (a type of white
blood cells) in the blood.
This disease is more intense in people who never
have been exposed to lymphatic filariasis than it is in
the native people of tropical areas where the disease
occurs. This is because many of the native people often
are immunologically tolerant.
1293

Elephantiasis

‘‘lymphedema.’’ Limbs can swell so enormously that
they resemble an elephant’s foreleg in size, texture, and
color. This is the severely disfiguring and disabling
condition of elephantiasis.

Elephantiasis

Diagnosis
The only sure way to diagnose lymphatic filariasis
is by detecting the parasite itself, either the adult
worms or the microfilariae.
Microscopic examination of the person’s blood may
reveal microfilariae. But many times, people who have
been infected for a long time do not have microfilariae in
their bloodstream. The absence of them, therefore, does
not mean necessarily that the person is not infected. In
these cases, examining the urine or hydrocele fluid or
performing other clinical tests is necessary.
Collecting blood from the individual for microscopic examination should be done during the night
when the microfilariae are more numerous in the
bloodstream. (Interestingly, this is when mosquitoes
bite most frequently.) During the day microfilariae
migrate to deeper blood vessels in the body, especially
in the lung. If it is decided to perform the blood test
during the day, the infected individual may be given a
‘‘provocative’’ dose of medication to provoke the
microfilariae to enter the bloodstream. Blood then
can be collected an hour later for examination.
Detecting the adult worms can be difficult because
they are deep within the lymphatic system and difficult
to get to. Biopsies usually are not performed because
they usually don’t reveal much information.

Treatment
The drug of choice in treating lymphatic filariasis
is diethylcarbamazine (DEC). The trade name in the
United States is Hetrazan.

Man suffering from elephantiasis. (Photograph by C. James
Webb, Phototake NYC. Reproduced by permission.)

The treatment schedule is typically 2 mg/kg per
day, three times a day, for three weeks. The drug is
taken in tablet form.

individual. Side effects may include fever, chills, headache, dizziness, nausea and vomiting, itching, and joint
pain. These side effects usually occur within the first
few days of treatment. These side effects usually subside as the individual continues taking the drug.

DEC kills the microfilariae quickly and injures or
kills the adult worms slowly, if at all. If all the adult
worms are not killed, remaining paired males and
females may continue to produce more larvae.
Therefore, several courses of DEC treatment over a
long time period may be necessary to rid the individual
of the parasites.
DEC has been shown to reduce the size of
enlarged lymph nodes and, when taken long-term, to
reduce elephantiasis. In India, DEC has been given in
the form of a medicated salt, which helps prevent
spread of the disease.
The side effects of DEC almost all are due to the
body’s natural allergic reactions to the dying parasites
rather than to the DEC itself. For this reason, DEC
must be given carefully to reduce the danger to the
1294

There is an alternate treatment plan for the use of
DEC. This plan is designed to kill the parasites slowly
(to reduce allergic reactions to the dead microfilariae
and dying adult worms within the body). Lower doses
of DEC are taken for the first few days, followed by
the higher dose of 2 mg/kg per day for the remaining
three weeks. In addition, steroids may be prescribed to
prevent the individual’s body from reacting severely to
the dead worms.
Another drug used is Ivermectin. Early research
studies of Ivermectin show that it is excellent in killing
microfilariae, but the effects of this drug on the adult
worms are still being investigated. It is probable that
patients will need to continue using DEC to kill the
GALE ENCYCLOPEDIA OF MEDICINE

Antigen—Any substance (usually a protein) that
causes an immune response by the body to produce
antibodies.
Filarial—Threadlike. The word ‘‘filament’’ is
formed from the same root word.
Host—A person or animal in which a parasite lives,
is nourished, grows, and reproduces.
Lymph—A watery substance that collects in the
tissues and organs of the body and eventually
drains into the bloodstream.
Lymphatic system—A network composed of vessels, lymph nodes, the tonsils, the thymus gland,
and the spleen. It is responsible for transporting
fluid and nutrients to the bloodstream and for
maturing certain blood cells that are part of the
body’s immune system.
Lymphedema—The unnatural accumulation of
lymph in the tissues of the body, which results in
swelling in that area.
Protozoa—(Plural form of protozoan) Single-celled
organisms (not bacteria) of which about 30 kinds
cause disease in humans.
Streptococcal—Pertaining to any of the
Streptococcus bacteria. These organisms can
cause pneumonia, skin infections, and many other
diseases.

adult worms. Mild side effects of Ivermectin include
headache, fever, and myalgia.
Other means of managing lymphatic filariasis are
pressure bandages to wrap the swollen limb and elastic
stockings to help reduce the pressure. Exercising and
elevating a bandaged limb also can help reduce its size.
Surgery can be performed to reduce elephantiasis
by removing excess fatty and fibrous tissue, draining
the swelled area, and removing the dead worms.

Prognosis
With DEC treatment, the prognosis is good for
early and mild cases of lymphatic filariasis. The prognosis is poor, however, for heavy parasitic infestations.

Prevention
The two main ways to control this disease are to
take DEC preventively, which has shown to be
GALE ENCYCLOPEDIA OF MEDICINE

effective, and to reduce the number of carrier insects
in a particular area.
Avoiding mosquito bites with insecticides and
insect repellents is helpful, as is wearing protective
clothing and using bed netting.
Much effort has been made in cleaning the breeding sites (stagnant water) of mosquitoes near people’s
homes in areas where filariasis is found.
Before visiting countries where lymphatic filariasis is found, it would be wise to consult a travel physician to learn about current preventative measures.
Resources
ORGANIZATIONS

National Lymphedema Network. 2211 Post St., Suite 404,
San Francisco, CA 94115. (800) 541-3259. <http://
www.hooked.net>.
National Organization for Rare Disorders. PO Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Collette L. Placek

ELISA (Enzyme-linked Immunosorbant see
AIDS tests

I Embolism
Definition
An embolism is an obstruction in a blood vessel
due to a blood clot or other foreign matter that gets
stuck while traveling through the bloodstream. The
plural of embolism is emboli.

Description
Emboli have moved from the place where they
were formed through the bloodstream to another
part of the body, where they obstruct an artery and
block the flow of blood. The emboli are usually
formed from blood clots but are occasionally comprised of air, fat, or tumor tissue. Embolic events can
be multiple and small, or single and massive. They can
be life-threatening and require immediate emergency
medical care. There are three general categories of
emboli: arterial, gas, and pulmonary. Pulmonary
emboli are the most common.
1295

Embolism

KEY TERMS

Embolism

complications of deep vein thrombosis, blood clots in
the deep vein of the leg or pelvis.

Causes and symptoms

A close up view of a pulmonary embolism. (Custom Medical
Stock Photo. Reproduced by permission.)

Arterial embolism
In arterial emboli, blood flow is blocked at the
junction of major arteries, most often at the groin,
knee, or thigh. Arterial emboli are generally a complication of heart disease. An arterial embolism in the
brain (cerebral embolism) causes stroke, which can
be fatal. An estimated 5–14% of all strokes are caused
by cerebral emboli. Arterial emboli to the extremities
can lead to tissue death and amputation of the affected
limb if not treated effectively within hours. Intestines
and kidneys can also suffer damage from emboli.
Gas embolism
Gas emboli result from the compression of
respiratory gases into the blood and other tissues due
to rapid changes in environmental pressure, for example, while flying or scuba diving. As external pressure
decreases, gases (like nitrogen) that are dissolved in the
blood and other tissues become small bubbles that can
block blood flow and cause organ damage.
Pulmonary embolism
In a pulmonary embolism, a common illness, blood
flow is blocked at a pulmonary artery. When emboli
block the main pulmonary artery, and in cases where
there are no initial symptoms, a pulmonary embolism
can quickly become fatal. According to the American
Heart Association, an estimated 600,000 Americans
develop pulmonary emboli annually and 60,000 die
from it.
A pulmonary embolism is difficult to diagnose.
Less than 10% of patients who die from a pulmonary
embolism were diagnosed with the condition. More
than 90% of cases of pulmonary emboli are
1296

Arterial emboli are usually a complication of
heart disease where blood clots form in the heart’s
chambers. Gas emboli are caused by rapid changes in
environmental pressure that could happen when flying
or scuba diving. A pulmonary embolism is caused by
blood clots that travel through the blood stream to the
lungs and block a pulmonary artery. More than 90%
of the cases of pulmonary embolism are a complication of deep vein thrombosis, which typically occurs in
patients who have had orthopedic surgery and patients
with cancer or other chronic illnesses like congestive
heart failure.
Risk factors for arterial and pulmonary emboli
include: prolonged bed rest, surgery, childbirth, heart
attack, stroke, congestive heart failure, cancer, obesity, a broken hip or leg, oral contraceptives, sickle
cell anemia, chest trauma, certain congenital heart
defects, and old age. Risk factors for gas emboli
include: scuba diving, amateur plane flight, exercise,
injury, obesity, dehydration, excessive alcohol, colds,
and medications such as narcotics and antihistamines.
Symptoms of an arterial embolism include:


severe pain in the area of the embolism



pale, bluish cool skin



numbness



tingling



muscular weakness or paralysis

Common symptoms of a pulmonary embolism
include:


labored breathing, sometimes accompanied by chest
pain



a rapid pulse



a cough that may produce sputum



a low-grade fever



fluid build-up in the lungs
Less common symptoms include:



coughing up blood



pain caused by movement or breathing



leg swelling



bluish skin



fainting



swollen neck veins
GALE ENCYCLOPEDIA OF MEDICINE

An embolism can be diagnosed through the
patient’s history, a physical exam, and diagnostic
tests. The use of various tests may change, as physicians and clinical guidelines evaluate the most effective
test in terms of accuracy and cost. For arterial emboli,
cardiac ultrasound and/or arteriography are ordered.
For a pulmonary embolism, a chest x ray, lung scan,
pulmonary angiography, electrocardiography, arterial
blood gas measurements, and venography or venous
ultrasound could be ordered.
Diagnosing an arterial embolism
Ultrasound uses sound waves to create an image
of the heart, organs, or arteries. The technologist
applies gel to a hand-held transducer, then presses it
against the patient’s body. The sound waves are converted into an image that can be displayed on a monitor. Performed in an outpatient diagnostic laboratory,
the test takes 30–60 minutes.
An arteriogram is an x ray in which a contrast
medium is injected to make the arteries visible. It can
be performed in a radiology unit, outpatient clinic, or
diagnostic center of a hospital.
Diagnosing a pulmonary embolism
A chest x ray can show fluid build-up and detect
other respiratory diseases. The perfusion lung scan
shows poor flow of blood in areas beyond blocked
arteries. The patient inhales a small amount of radiopharmaceutical and pictures of airflow into the lungs
are taken with a gamma camera. Then a different
radiopharmaceutical is injected into an arm vein and
lung blood flow is scanned. A normal result essentially
rules out a pulmonary embolism. A lung scan can be
performed in a hospital or an outpatient facility and
takes about 45 minutes.

legs. Impulses of the heart’s activity are traced on
paper. The test takes about 10 minutes.
Arterial blood gas measurements are sometimes
helpful but, alone, they are not diagnostic for pulmonary embolism. Blood is taken from an artery instead of
a vein, usually in the wrist.
Venography is used to look for the most likely
source of a pulmonary embolism, deep vein thrombosis. It is very accurate, but it is not used often, because
it is painful, expensive, exposes the patient to a fairly
high dose of radiation, and can cause complications.
Venography identifies the location, extent, and degree
of attachment of the blood clots and enables the condition of the deep leg veins to be assessed. A contrast
solution is injected into a foot vein through a catheter.
The physician observes the movement of the solution
through the vein with a fluoroscope while a series of
x rays are taken. Venography takes between 30–45
minutes and can be done in a physician’s office, a
laboratory, or a hospital. Radionuclide venography,
in which a radioactive isotope is injected, is occasionally used, especially if a patient has had reactions to
contrast solutions. Venous ultrasound is the preferred
evaluation of leg veins.
As noninvasive methods such as high-speed computed tomography (CT) scanning improve, they may
be used to diagnose emboli. For instance, spiral (also
called helical) CT scans may be the preferred tool for
diagnosing pulmonary embolism in pregnant women.

Treatment

Pulmonary angiography is one of the most reliable tests for diagnosing a pulmonary embolism.
Pulmonary angiography is a radiographic test that
involves injection of a radio contrast agent to show
the pulmonary arteries. A cinematic camera records
the blood flow through the patient, who lies on a table.
Pulmonary angiography is usually performed in a
hospital’s radiology department and takes 30–60
minutes.

Patients with emboli require immediate hospitalization. They are generally treated with clot-dissolving
and/or clot-preventing drugs. Thrombolytic therapy to
dissolve blood clots is the definitive treatment for a
severe pulmonary embolism. Streptokinase, urokinase, and recombinant tissue plasminogen activator
(TPA) are used. Heparin has been the anticoagulant
drug of choice for preventing formation of blood clots.
A new drug has been approved for treatment of acute
pulmonary emboli. Called fondaparinux (Arixtra), it
usually is administered with Warfarin, an oral anticoagulant. Warfarin is sometimes used with other
drugs to treat acute embolism events and is usually
continued after the hospitalization to help prevent
future emboli. Arixtra also has been used on an
ongoing basis to prevent pulmonary emboli.

An electrocardiograph shows the heart’s electrical
activity and helps distinguish a pulmonary embolism
from a heart attack. Electrodes covered with conducting jelly are placed on the patient’s chest, arms, and

In the case of an arterial embolism, the affected
limb is placed in a dependent position and kept warm.
Embolectomy is the treatment of choice in the majority of early cases of arterial emboli in the extremities.

GALE ENCYCLOPEDIA OF MEDICINE

1297

Embolism

Diagnosis

Emergency contraception

In this procedure, a balloon-tipped catheter is inserted
into the artery to remove thromboembolic matter.
With a pulmonary embolism, oxygen therapy is
often used to maintain normal oxygen concentrations.
For people who can’t take anticoagulants and in some
other cases, surgery may be needed to insert a device
that filters blood returning to the heart and lungs.

Prognosis
Of patients hospitalized with an arterial embolism, 25–30% die, and 5–25% require amputation of
a limb. About 10% of patients with a pulmonary
embolism die suddenly within the first hour of onset
of the condition. The outcome for all other patients is
generally good; only 3% of patients die who are
properly diagnosed early and treated. In cases of an
undiagnosed pulmonary embolism, about 30% of
patients die.

Prevention

KEY TERMS
Anticoagulants—Drugs that suppress, delay, or
prevent blood clots. Anticoagulants are used to
treat embolisms.
Artery—A blood vessel that carries blood from the
heart to other body tissues. Embolisms obstruct
arteries.
Deep vein thrombosis—A blood clot in the calf’s
deep vein. This frequently leads to pulmonary
embolism if untreated.
Emboli—Clots or other substances that travel
through the blood stream and get stuck in an artery,
blocking circulation.
Thrombolytics—Drugs that dissolve blood clots.
Thrombolytics are used to treat embolisms.

Resources

Embolism can be prevented in high risk patients
through antithrombotic drugs such as heparin, venous
interruption, gradient elastic stockings, and intermittent pneumatic compression of the legs. The combination of graduated compression stockings and low-dose
heparin is significantly more effective than low-dose
heparin alone.

PERIODICALS

Gradient elastic stockings, also called antiembolism stockings, decrease the risk of blood clots
by compressing superficial leg veins and forcing blood
into the deep veins. They can be knee-, thigh-, or waistlength. Many physicians order the use of stockings
before surgery and until there is no longer an elevated
risk of developing blood clots. The risk of deep vein
thrombosis after surgery is reduced 50% with the use
of these stockings. The American Heart Association
recommends that the use of graduated compression
stockings be considered for all high-risk surgical
patients.

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Intermittent pneumatic compression involves
wrapping knee- or thigh-high cuffs around the legs to
prevent blood clots. The cuffs are connected to a pump
that inflates and deflates, mimicking the heart’s normal pumping action and reducing the pooling of
blood. Intermittent pneumatic compression can be
used during surgery and recovery and continues until
there is no longer an elevated risk of developing blood
clots. The American Heart Association recommends
the use of intermittent pneumatic compression for
patients who cannot take anticoagulants, for example,
spinal cord and brain trauma patients.
1298

Doyle, Nora M., et al. ‘‘Diagnosis of Pulmonary Embolism:
A Cost-effective Analysis.’’ American Journal of
Obstetrics and Gynecology September 2004: 1019–1024.
Truelove, Christiane. ‘‘First for Pulmonary Embolism.’’
Med Ad News August 2004: 82.
ORGANIZATIONS

Lori De Milto
Teresa G. Odle

I Emergency contraception
Definition
Emergency contraception or emergency birth control uses either emergency contraceptive pills (ECPs)
or a Copper-T intrauterine device (IUD) to help prevent pregnancy following unprotected vaginal
intercourse.

Purpose
Emergency contraception may be used to prevent
pregnancy after vaginal intercourse when:
GALE ENCYCLOPEDIA OF MEDICINE

A birth control method was not used. Young people,
in particular, may not be prepared for their first
experience of sexual intercourse.



A condom broke or slipped and ejaculation occurred
within the woman’s vagina.



The male failed to withdraw from the vagina before
ejaculation.



A woman failed to take her birth control pills.



A diaphragm, cap, or shield slipped out of place,
followed by ejaculation within the vagina.



A woman’s ‘‘safe days’’ were miscalculated.



A woman was raped or otherwise forced to have
unprotected intercourse.

Women who missed taking their oral contraceptives may consider emergency contraception if:

Almost all women can use emergency contraception safely, even those who cannot use oral contraceptives as a regular method of birth control because
of heart disease, blood clots, stroke, or other cardiovascular problems. The anti-convulsive medication
Dilantin may reduce the effectiveness of ECPs. Some
physicians recommend doubling the first of the two
ECP doses if taken with Dilantin.
Progestin-only ECPs (POPs) are not recommended for women who:


may be pregnant already



have a hypersensitivity to any component of the
medication



have abnormal, undiagnosed genital bleeding.

Copper-T IUDs should not be used for emergency
contraception if a woman:


is pregnant

A new packet of pills was started at least two days
late.



has a history of pelvic inflammatory disease (PID)
that has impaired her fertility



Two to four of the first seven active (hormone-containing) pills (days 1–7) were missed.



has one of numerous other conditions affecting her
reproductive system



Five or more active pills were missed consecutively.



has—or is currently at risk for contracting—a sexually transmitted disease (STD) such as HIV/AIDS,
chlamydia, or gonorrhea, since IUD insertion can
introduce infectious agents into the sterile uterine
cavity.



On average eight out of every 100 fertile women
will become pregnant after having one episode of
unprotected vaginal intercourse during the second or
third week of their menstrual cycle. Following treatment with combined ECPs, only two of those 100
women will become pregnant—a 75% reduction.
Following treatment with progestin-only ECPs, only
one woman out of the 100 will become pregnant—an
89% reduction. Following emergency insertion of an
IUD there is a 99.9% reduction in the risk of
pregnancy.

Precautions
Emergency contraception does not work after the
onset of pregnancy; nor should it be used as a regular
method of birth control. ECPs do not prevent pregnancy from intercourse that occurs following the
treatment; another birth control method must be
used to prevent pregnancy. Although ECPs will not
affect an existing pregnancy and will not harm the
fetus, emergency contraception should not be used if
a woman is already pregnant.
Frequent use of ECPs can result in irregular or
unpredictable menstrual periods. Additional doses of
ECPs usually do not reduce the risk of pregnancy and
they increase the risk of side effects including nausea
and vomiting.
GALE ENCYCLOPEDIA OF MEDICINE

Those at risk for contracting an STD include
women who:


have been raped



have had unprotected sex with a new partner



are in a non-monogamous relationship



use intravenous drugs



have partners who use intravenous drugs

Description
Although emergency contraception—sometimes
called post-coital or morning-after contraception—
has been available for over a quarter of a century,
almost one-half of the 6.3 million pregnancies in the
United States each year are unintended. Among teen
pregnancies 80% are unintentional. About one-half of
unintended pregnancies are caused by contraceptive
failure, either a failure of the method or a mistake by
the user. The remainder of unintended pregnancies
occurs because birth control was not employed.
Emergency contraception could help prevent some of
the 1.4 million abortions that take place in the United
States every year.
1299

Emergency contraception



Emergency contraception

Emergency contraception prevents pregnancy by
one of the following methods:



Aviane, manufactured by Duramed; five orange pills
per dose



delaying or inhibiting ovulation—the release of eggs
from the ovary



Cryselle, manufactured by Barr; four white pills per
dose



altering the transport of the sperm or egg, thereby
preventing fertilization of the egg by a sperm



Enpresse from Barr; four orange pills per dose



Lessina from Barr; five pink pills per dose



altering the endometrium or uterine lining, thereby
preventing implantation—the attachment of the fertilized egg to the wall of the uterus



Levlen from Berlex; four light orange pills per dose



Levlite from Berlex; five pink pills per dose



Levora from Watson; four white pills per dose



Lo/Ovral from Wyeth-Ayerst; four white pills per
dose



Low-Ogestrel from Watson; four white pills per dose



Lutera from Watson; five white pills per dose



Nordette from Wyeth-Ayerst; four light orange pills
per dose



Ogestrel from Watson; two white pills per dose



Ovral from Wyeth-Ayerst; two white pills per dose



Portia from Barr; four pink pills per dose



Seasonale from Barr; four pink pills per dose



Tri-Levlen from Berlex; four yellow pills per dose



Triphasil from Wyeth-Ayerst; four yellow pills per
dose



Trivora from Watson; four pink pills per dose

The mechanism by which ECPs prevent pregnancy
depends on the stage of the woman’s menstrual cycle.
In most cases ECPs delay or inhibit ovulation and have
no effect on implantation. IUDs used as emergency
contraception appear to interfere with implantation
of the fertilized egg; although they also may prevent
fertilization, as they are thought to do when they are
used as a regular method of birth control.
Emergency contraceptive pills (ECPs)
ECPs contain synthetic hormones that mimic the
hormones produced by a woman’s body. Many common brands of birth control pills can be used for emergency contraception even though they are not labeled
for that use. Any of the first 21 pills in a regular 28-pill
package of oral contraceptives can be used for emergency contraception. The last seven pills in 28-pill packs
do not contain hormones. The number of pills that
constitute an emergency contraceptive dose depends
on the brand of pill. The same brand should be used
for both doses of ECPs. Many ECPs are available outside of the United States, where they are packaged,
labeled, and sold for emergency contraceptive purposes.
COMBINED ECPS. Combined ECPs available in the
United States contain 100 micrograms of the synthetic
estrogen, ethinyl estradiol, and 0.5–0.6 mg of the synthetic progestin levonorgestrel per dose. Combined
ECPs are taken according to the Yuzpe Regimen,
named after A. Albert Yuzpe, the Canadian researcher
who first demonstrated their safety and effectiveness in
1974. With the Yuzpe Regimen, the first dose of combined ECPs is taken as soon as possible after unprotected intercourse and the second dose is taken 12
hours later. However the timing of the second dose
can vary by a few hours without diminishing its effectiveness. The Preven Emergency Contraceptive Kit—
the first product to be specifically labeled and marketed
for emergency contraception—is no longer available.

Combined ECPs available in the United States
include:


Alesse, manufactured by Wyeth-Ayerst; five pink
pills per dose

1300

PROGESTIN-ONLY
ECPS. Progestin-only
ECPs
(POPs) are prescribed frequently, particularly for
women who cannot take estrogen or who are breastfeeding. POPs contain 0.75 mg of levonorgestrel per
dose. They are equally effective regardless of whether
the two doses are taken simultaneously or 12–24 hours
apart. POPs are most effective if taken within 72 hours
of unprotected intercourse; however they reduce the
risk of pregnancy if taken within 120 hours.

Progestin-only pills include:


Plan B from Barr is the only drug available in the
United States that is specifically designed and designated as an ECP—one white pill per dose.



Ovrette from Wyeth-Ayerth requires swallowing 20
yellow pills for each dose.
The Copper-T IUD

The Copper-T 380A IUD (ParaGard) is a
T-shaped device that provides emergency contraception if inserted into the uterus by a healthcare provider
within seven days after unprotected intercourse. It can
be removed by the healthcare provider after the
woman’s next menstrual period begins or it can remain
GALE ENCYCLOPEDIA OF MEDICINE

Availability
In most of the United States, emergency contraception requires a special prescription or a prescription for a monthly supply of an appropriate
oral contraceptive. Most physicians do not routinely discuss the use of emergency contraception
with their patients and some pharmacies refuse to
carry ECPs.
Emergency contraception is available from:


public and college health clinics



women’s health centers



Planned Parenthood clinics



private doctors



hospital emergency rooms, except those affiliated
with a religion that opposes the use of birth control



pharmacists directly, in a small number of states.

Some healthcare providers may prescribe ECPs
over the telephone. Sexual assault victims may be
offered ECPs in the hospital emergency room.
In many countries ECPs are available without a
prescription. However in the United States emergency
contraception remains controversial. In September of
2004, the U. S. Department of Justice released guidelines for the treatment of sexual assault victims without mentioning the option of emergency
contraception. As of early 2005, the U.S. Food and
Drug Administration (FDA) had delayed approval of
over-the-counter (OTC) status for Plan B. However
many professional healthcare organizations and advocacy groups for women’s reproductive rights were
working to make ECPs available without a prescription in the United States.
Costs
The cost of emergency contraception varies
greatly according to region and location and any additional required services. Family-planning clinics and
public healthcare centers may provide lower-cost
emergency contraception or charge according to an
income-based sliding scale.
As of 2005, estimated costs for emergency contraception were:


$8–$35 for Plan B



$20–$50 for combined ECPs



$50–$70 for other progestin-only ECPs

GALE ENCYCLOPEDIA OF MEDICINE



$35–$150 for a visit to a healthcare provider



$10–$20 for a pregnancy test



about $400 for an exam, IUD, and insertion; however the IUD can remain in place for up to 12 years.

Preparation
For emergency contraception to be effective, it
must be used as soon as possible following unprotected intercourse. Some healthcare providers and
women’s health centers prescribe or supply packets
of ECPs—called EC-to-Go—so that they are available immediately if required. Supplies of ECPs are
particularly important for women who are at high
risk for having unprotected intercourse. EC-to-Go
also avoids the cost of an extra visit to a healthcare
provider.
Studies have found that neither the use of ECPs,
nor having a supply of ECPs on hand, reduce the
likelihood that women, including teenagers, will use
conventional contraceptive methods. In fact it has
been shown that the use of ECPs often increases the
likelihood that a regular birth control method will be
employed.
If an office visit is required, a healthcare provider
may take a medical history, perform a pregnancy test
on a urine sample, and—provided that pregnancy has
not occurred—discuss the appropriate type of emergency contraception.

Aftercare
For about 10–15% of women who take ECPs, the
timing, duration, and/or amount of bleeding for their
next menstrual period may be different than usual.
About 50% of women have their first post-ECP menstrual period one to three days earlier or later than
expected. Most often it is earlier than expected.
Bleeding may be normal or heavier, lighter, or more
spotty than usual.
Following IUD insertion, a woman may need to
be escorted or driven home and she may require rest.

Risks
Emergency contraception is considered to be
both safe and effective for teenagers as well as
adult women. However emergency contraception
may not prevent an ectopic pregnancy—a pregnancy outside of the uterus, in the fallopian tubes
or abdomen. Ectopic pregnancies are medical emergencies and can be fatal.
1301

Emergency contraception

in place for up to 10–12 years as an effective method of
birth control.

Emergency contraception

Side effects of ECPs

KEY TERMS

About 50% of women feel sick to their stomachs
for approximately 24 hours after taking combined
ECPs. Nausea occurs in 30–50% of women and
15–25% of women experience vomiting. Only 23% of
women who take progestin-only ECPs experience nausea and only 6% have vomiting.

Emergency contraceptive pills; ECPs—Medication
containing synthetic hormones for preventing pregnancy after unprotected vaginal intercourse.
Endometrium—The lining of the uterus.
Ethinyl estradiol—A semi-synthetic derivative of
estradiol—an estrogen or female sex hormone—
used in birth control pills and combined ECPs.
Implantation—The embedding of a fertilized egg
in the inner wall of the uterus.

If vomiting occurs within one hour of taking
ECPs, the dose may have to be repeated. OTC medications such as Dramamine II, Bonine, or their generic
equivalents, taken one hour before the ECPs, reduce
the risk of nausea and vomiting, although they may
cause drowsiness. Two 25-mg tablets of Meclizine,
taken one hour before the ECPs, reduce the risk of
nausea by 27% and the risk of vomiting by 64%;
however there is about a 30% risk of drowsiness. If
vomiting occurs after the first dose of an ECP, antinausea medication should be taken one hour before
the second dose. The second dose also may be taken as
a vaginal suppository by placing the pills as far as
possible into the vagina for absorption through the
vaginal tissue.

Intrauterine device; IUD—A device inserted into
the uterus to prevent pregnancy.
Levonorgestel—A synthetic progestin used in
ECPs.
Ovulation—The discharge of an ovum (egg) from
the mature follicle of the ovary.
Progestin—A synthetic or natural drug that acts on
the uterine lining.
Yuzpe Regimen—A two-dose treatment with combined ECPs to prevent pregnancy after unprotected
intercourse; the first dose is taken as soon as possible and the second dose is taken 12 hours after
the first.

Other side effects of ECPs can include:


breast tenderness



abdominal pain



irregular bleeding



dizziness



headaches



fatigue.

Side effects usually last only one to two days and
are far less frequent with progestin-only ECPs as compared with combined ECPs.
Side effects of IUD insertion
Side effects of IUD insertion may include:


abdominal discomfort



vaginal bleeding or spotting



infection.

However the risk of pelvic infection is very small
among women who are not at risk for STDs.
Other possible side effects of IUD insertion
include:


heavy menstrual flow



cramping



infertility



uterine puncture.

1302

Normal results
The effectiveness of emergency contraception
depends both on the stage of the woman’s menstrual
cycle and on how soon the emergency contraception is
used following unprotected vaginal intercourse. The
closer a woman is to ovulation—her fertile period
during which eggs are released from the ovary—the
less effective emergency contraception will be.
ECPs are less effective than the most popular birth
control methods:


If taken within 72 hours of unprotected intercourse,
combined ECPs are about 75% effective for preventing pregnancy.



Progestin-only ECPs are 95% effective if taken
within 24 hours of unprotected intercourse and
about 89% effective if taken within 72 hours.



A Copper-T IUD is 99.9% effective if inserted within
seven days of unprotected intercourse.

If a normal menstrual period does not begin
within three weeks after taking ECPs, or if signs of
pregnancy develop, a healthcare provider should be
consulted immediately.
GALE ENCYCLOPEDIA OF MEDICINE



a missed menstrual period



nausea



unexplained fatigue

Planned Parenthood Federation of America, Inc. 434 West
33rd Street, New York, NY 10001. 800-230-7562
(PLAN). <http://www.plannedparenthood.org>.
U.S. Food and Drug Administration. 5600 Fishers Lane,
Rockville MD 20857-0001. 888-INFO-FDA (888-4636332). <http://www.fda.gov>.



enlarged or sore breasts

OTHER



headaches



frequent urination

Emergency Contraception. Planned Parenthood. February
2005 [cited March 6, 2005]. <http://
www.plannedparenthood.org/pp2/portal/medicalinfo/
ec/pub-emergency-contraception.xml>.
Emergency Contraception. Planned Parenthood. June 2004
[cited March 6, 2005]. <http://
www.plannedparenthood.org/pp2/portal/medicalinfo/
ec/fact-emergency-contraception.xml>.
Frequently Asked Questions About Emergency
Contraception. The National Women’s Health
Information Center. November 2002 [cited March 6,
2005]. <http://www.4woman.gov/faq/
econtracep.htm>.
Not-2-Late.com. The Emergency Contraception Website.
Office of Population Research, Princeton University
and the Association of Reproductive Health
Professionals. [Cited March 6, 2005]. <http://
ec.princeton.edu>.

The majority of women express satisfaction with
emergency contraception. One study of 235 women
who had used ECPs found that 91% were satisfied
with the method and 97% would recommend it to
others.
Resources
BOOKS

Emergency Contraception: A Medical Dictionary,
Bibliography, and Annotated Research Guide to Internet
References. Icon Health Publications, 2004.
The Essential Guide for Emergency Contraception. American
Healthcare Consultants, 2004.
PERIODICALS

Brody, Jane E. ‘‘The Politics of Emergency Contraception.’’
New York Times August 24, 2004: F.7.
Cantor, Julie, and Ken Baum. ‘‘The Limits of Conscientious
Objection—May Pharmacists Refuse to Fill
Prescriptions for Emergency Contraception?’’ New
England Journal of Medicine 351, no. 19 (November 4,
2004): 2008–12.
Raine, Tina R., et al. ‘‘Direct Access to Emergency
Contraception Through Pharmacies and Effect on
Unintended Pregnancy and STIs.’’ Journal of the
American Medical Association 293, no. 1 (January 5,
2005): 54–62.
Weismiller, David G. ‘‘Emergency Contraception.’’
American Family Physician 70, no. 4 (August 15, 2004):
707–14.
ORGANIZATIONS

Association of Reproductive Health Professionals. 2401
Pennsylvania Avenue NW, Suite 350, Washington, DC
20037. 202-466-3825. <http://arhp.org>.
The Emergency Contraception for Diverse Communities
Project, Program for Appropriate Technology in
Health (PATH). 1455 NW Leary Way, Seattle, WA
98107-5136. 206-285-3500. <http://www.path.org>.
National Women’s Health Information Center, Office on
Women’s Health, U.S. Department of Health and
Human Services. 8550 Arlington Blvd., Suite 300,
Fairfax, VA 22031. 800-994-WOMAN (9662). <http://
www.4woman.gov>.
Office of Population Research, Princeton University.
Wallace Hall, Princeton, NJ 08544. 609-258-4870.
<http://opr.princeton.edu>.
GALE ENCYCLOPEDIA OF MEDICINE

Margaret Alic, Ph.D.

EMG see Electromyography
Emollient bath see Therapeutic baths

I Emphysema
Definition
Emphysema is a chronic respiratory disease where
there is over-inflation of the air sacs (alveoli) in the
lungs, causing a decrease in lung function, and often,
breathlessness.

Description
Emphysema is the most common cause of death
from respiratory disease in the United States, and is
the fourth most common cause of death overall. There
are 1.8 million Americans with the disease, which
ranks fifteenth among chronic conditions that cause
limitations of activity. The disease is usually caused by
smoking, but a small number of cases are caused by an
inherited defect.
Normally functioning lungs are elastic, efficiently
expanding and recoiling as air passes freely through
1303

Emphysema

Signs of pregnancy include:

Emphysema

the bronchus to the alveoli, where oxygen is moved
into the blood and carbon dioxide is filtered out.
When a person inhales cigarette smoke or certain
other irritants, his or her immune system responds by
releasing substances that are meant to defend the lungs
against the smoke. These substances can also attack
the cells of the lungs, but the body normally inhibits
such action with the release of other substances. In
smokers and those with the inherited defect, however,
no such prevention occurs and the lung tissue is
damaged in such a way that it loses its elasticity. The
small passageways (bronchioles) leading to the alveoli
collapse, trapping air within the alveoli. The alveoli,
unable to recoil efficiently and move the air out, over
expand and rupture. As the disease progresses, coughing and shortness of breath occur. In the later stages,
the lungs cannot supply enough oxygen to the blood.
Emphysema often occurs with other respiratory diseases, particularly chronic bronchitis. These two
diseases are often referred to as one disorder called
chronic obstructive pulmonary disease (COPD).
Emphysema is most common among people aged
50 and older. Those with inherited emphysema may
experience the onset as early as their thirties or forties.
Men are more likely than women to develop emphysema, but female cases are increasing as the number of
female smokers rises.

Causes and symptoms
Heavy cigarette smoking causes about 80–90% of
all emphysema cases. However a few cases are the
result of an inherited deficiency of a substance called
alpha-1-antitrypsin (AAT). The number of Americans
with this deficiency is relatively small, probably no
greater than 70,000. Pipe, cigar, and marijuana smoking can also damage the lungs. While a person may be
less likely to inhale cigar and pipe smoke, these types
of smoke can also impair lung function. Marijuana
smoke may be even more damaging because it is
inhaled deeply and held in by the smoker.
The symptoms of emphysema develop gradually
over many years. It is a common occurrence for many
emphysema patients to have lost over half of their
functioning lung tissue before they become aware
that something is wrong. Shortness of breath, a chronic
mild cough (which may be productive of large amounts
of dark, thick sputum, and often dismissed as ‘‘smoker’s cough’’), and sometimes weight loss are associated with emphysema. Initially, a patient may only
notice shortness of breath when he or she is exercising.
However, as the disease progresses, it will occur with
less exertion or no exertion at all. Emphysema patients
1304

A scanning electron microscopy (SEM) of lung tissue indicating emphysema. (Photograph by Hossler, Ph.D., Custom
Medical Stock Photo. Reproduced by permission.)

may also develop an enlarged, or ‘‘barrel,’’, chest.
Other symptoms may be skipped breaths, difficulty
sleeping, morning headaches, increased difficulty
breathing while lying down, chronic fatigue, and swelling of the feet, ankles, or legs. Those with emphysema
are at risk for a variety of other complications resulting from weakened lung function, including
pneumonia.

Diagnosis
A variety of pulmonary function tests may be
ordered. In the early stages of emphysema, the only
result may be dysfunction of the small airways.
Patients with emphysema may show an increase in
the total amount of air that is in the lungs (total lung
capacity), but a decrease in the amount of air that can
be breathed out after taking a deep breath (vital capacity). With severe emphysema, vital capacity is substantially below normal. Spirometry, a procedure that
measures air flow and lung volume, helps in the diagnosis of emphysema.
A chest x ray is often ordered to aid in the diagnosis of emphysema, though patients in the early
stages of the disease may have normal findings.
Abnormal findings on the chest x ray include overinflation of the lungs and an abnormally increased
chest diameter. The diaphragm may appear depressed
or flattened. In addition, patients with advanced
GALE ENCYCLOPEDIA OF MEDICINE

X ray showing emphysema in the lungs. (Photo Researchers.
Reproduced by permission.)

emphysema may show a smaller or vertical heart. The
physician may observe blisters in the lungs and bulging of the accessory muscles of the respiratory system. Late in the disease, an EKG will show signs of
right ventricular failure in the heart and increased
hemoglobin due to lower levels of oxygen in the
patient’s blood.

Treatment
Treatment methods for emphysema do not cure or
reverse the damage to the lungs. However, they may
slow the progression of the disease, relieve symptoms,
and help control possibly fatal complications. The first
step in treatment for smokers is to quit, so as to prevent any further deterioration of breathing ability.
Smoking cessation programs may be effective.
Consistent encouragement along with the help of
health care professionals as well as family and friends
can help increase the success rate of someone attempting to quit.
If the patient and the health care team develop
and maintain a complete program of respiratory care,
disability can be decreased, acute episodes of illness
may be prevented, and the number of hospitalizations
reduced. However, only quitting smoking has been
shown to slow down the progression of the disease,
and among all other treatments, only oxygen therapy
has shown an increase in the survival rate.
GALE ENCYCLOPEDIA OF MEDICINE

A variety of medications may be used in the treatment of emphysema. Usually the patient responds best to
a combination of medicines, rather than one single drug.
Bronchodilators are sometimes used to help alleviate the patient’s symptoms by relaxing and opening
the airways. They can be inhaled, taken by mouth, or
injected. Another category of medication often used is
corticosteroids or steroids. These help to decrease the
inflammation of the airway walls. They are occasionally used if bronchodilators are ineffective in preventing airway obstruction. Some patients’ lung function
improves with corticosteroids, and inhaled steroids
may be beneficial to patients with few side effects. A
variety of antibiotics are frequently given at the first
sign of a respiratory infection, such as increased
amounts of sputum, or if there has been a change in
the color of the sputum. Expectorants can help to
loosen respiratory secretions, enabling the patient to
more easily expel them from the airways.
Many of the medications prescribed involve the
use of a metered dose inhaler (MDI) that may require
special instruction to be used correctly. MDIs are a
convenient and safe method of delivering medication
to the lungs. However, if they are used incorrectly the
medication will not get to the right place. Proper technique is essential for the medication to be effective.
For some patients, surgical treatment may be the
best option. Lung volume reduction surgery is a surgical procedure in which the most diseased parts of the
lung are removed to enable the remaining lung
and breathing muscles to work more efficiently.
Preliminary studies suggest improved survival rates
and better functioning with the surgery. Another surgical procedure used for emphysema patients is lung
1305

Emphysema

Home oxygen therapy may improve the survival
times in those patients with advanced emphysema who
also have low blood oxygen levels. It may improve the
patient’s tolerance of exercise, as well as improve their
performance in certain aspects of brain function and
muscle coordination. The functioning of the heart may
also improve with an increased concentration of oxygen
in the blood. Oxygen may also decrease insomnia and
headaches. Some patients may only receive oxygen at
night, but studies have illustrated that it is most effective when administered at least 18, but preferably 24
hours per day. Portable oxygen tanks prescribed to
patients carry a limited supply and must be refilled on
a regular basis by a home health provider. Medicare
and most insurance companies cover a large proportion
of the cost of home oxygen therapy. Patients should be
instructed regarding special safety issues involving the
transport and presence of oxygen in the home.

Emphysema



Avoiding extreme temperatures of heat or cold. Also
avoiding high altitudes. (Special precautions can be
taken that may enable the emphysema patient to fly
on a plane.)



Maintaining adequate nutritional intake. Normally
a high protein diet taken in many small feedings is
recommended.

KEY TERMS
Alveoli—Small cells or cavities. In the lungs, these
are air sacs where oxygen enters the blood and
carbon dioxide is filtered out.
Pulmonary—Related to or associated with the
lungs.

Alternative treatment
transplantation. Transplantation may involve one or
both lungs. However, it is a risky and expensive procedure, and donor organs may not be available.
For those patients with advanced emphysema,
keeping the air passages reasonably clear of secretions
can prove difficult. Some common methods for mobilizing and removing secretions include:


Postural drainage. This helps to remove secretions
from the airways. The patient lies in a position that
allows gravity to aid in draining different parts of the
lung. This is often done after the patient inhales an
aerosol medication. The basic position involves the
patient lying on the bed with his chest and head over
the side and the forearms resting on the floor.



Chest percussion. This technique involves lightly
clapping the back and chest, and may help to loosen
thick secretions.



Coughing and deep breathing. These techniques may
aid the patient in bringing up secretions.



Aerosol treatments. These treatments may involve
solutions of saline, often mixed with a bronchodilator, which are then inhaled as an aerosol. The aerosols thin and loosen secretions. A treatment normally
takes 10 to 15 minutes, and is given three or four
times a day.

Patients with COPD can learn to perform a variety of self-help measures that may help improve their
symptoms and their ability to participate in everyday
activities. These measures include:


Avoiding any exposure to dusts and fumes.



Avoiding air pollution, including the cigarette smoke
of others.



Avoiding other people who have infections like the
cold or flu. Get a pneumonia vaccination and a yearly
flu shot.



Drinking plenty of fluids. This helps to loosen
respiratory secretions so they can be brought up
more easily through coughing.

1306

Many patients are interested in whether any alternative treatments for emphysema are available. Some
practitioners recommend supplements of antioxidant
nutrients. There have also been some studies indicating a correlation between a low Vitamin A levels and
COPD, with suggestions that supplements of vitamin
A might be beneficial. Aromatherapists have used
essential oils like eucalyptus, lavender, pine, and
rosemary to help relieve nasal congestion and make
breathing easier. The herb elecampane may act as an
expectorant to help patients clear mucus from the
lungs. The patient should discuss these remedies with
their health care practitioner prior to trying them, as
some may interact with the more traditional treatments that are already being used.

Prognosis
Emphysema is a serious and chronic disease that
cannot be reversed. If detected early, the effects and
progression can be slowed, particularly if the patient
stops smoking immediately. Complications of emphysema include higher risks for pneumonia and acute
bronchitis. Overall, the prognosis for patients with
emphysema is poor, with a survival rate for all those
with COPD of four years, and even less for emphysema. However, individual cases vary and many
patients can live much longer with supplemental oxygen and other treatment measures.

Prevention
The best way to prevent emphysema is to avoid
smoking. Even patients with inherited emphysema
should avoid smoking, as it especially worsens the
onset and severity. If patients quit smoking as soon
as evidence of small airway obstruction begins, they
can significantly improve their prognosis.
Resources
BOOKS

Beers, Mark H., and Robert Berkow, editors. The Merck
Manual ofDiagnosis and Therapy. Whitehouse Station,
NJ: Merck and Company, Inc., 2004.
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Data Mounting on Merits of Lung Volume
ReductionSurgery.’’ Family Practice News February
15, 2001: 5.
Lewis, Laurie. ‘‘Optimal Treatment for COPD.’’
PatientCare May 30, 2000: 60.
ORGANIZATIONS

American Lung Association. 1740 Broadway New York,
NY 10019. (212) 315-8700. <http://
www.lungusa.org>.
National Emphysema Foundation. 15 Stevens St. Norwalk,
CT 06856. <http://
www.emphysemafoundation.org>.
National Heart, Lung and Blood Institute. <http://
www.nhlbi.nih.gov>.

Deanna M. Swartout-Corbeil, R.N.

I Empyema
Definition
Empyema is a condition in which pus and fluid
from infected tissue collects in a body cavity. The
name comes from the Greek word empyein meaning
pus-producing (suppurate). Empyema is most often
used to refer to collections of pus in the space around
the lungs (pleural cavity), but sometimes refers to
similar collections in the gall bladder or the pelvic
cavity. Empyema in the pleural cavity is sometimes
called empyema thoracis, or empyema of the chest,
to distinguish it from empyema elsewhere in the body.

Description
Empyema may have a number of causes but is
most frequently a complication of pneumonia. Its
development can be divided into three phases: an
acute phase in which the body cavity fills with a thin
fluid containing some pus; a second stage in which the
fluid thickens and a fibrous, coagulation protein
(fibrin) begins to accumulate within the cavity; and a
third or chronic stage in which the lung or other organ
is encased within a thick covering of fibrous material.

through the bloodstream or other circulatory system, in
secretions from lung tissue, or on the surfaces of surgical
instruments or objects that cause open chest wounds. The
most common organisms that cause empyema are
the following bacteria: Streptococcus pneumoniae,
Haemophilus influenzae, and Staphylococcus aureus.
S. aureus is the most common cause in all age groups,
accounting for 90% of cases of empyema in infants and
children. Pelvic empyema in women is most often caused
by Bacteroides strains or Pseudomonas aeruginosa. In
elderly, chronically ill, or alcoholic patients, empyema is
often caused by Klebsiella pneumoniae species of bacteria.
When the disease organisms arrive in the cavity
surrounding the lungs, they infect the tissues that
cover the lungs and line the chest wall. As the body
attempts to fight off the infection, the cavity fills up
with tissue fluid, pus, and dead tissue cells. Empyema
of the gall bladder or pelvis results from similar reactions to infection in those parts of the body.
The signs and symptoms of empyema vary somewhat according to the location of the infection and its
severity. In empyema thoracis, patients usually exhibit
symptoms of pneumonia, including fever, cough, fatigue, shortness of breath, and chest pain. They may
prefer to lie on the side of the body affected by the
empyema. Family members may notice bad breath. In
severe cases, the patient may become dehydrated,
cough up blood or greenish-brown sputum, run a
fever as high as 1058F (40.68C), or fall into a coma.
Patients with thoracic empyema may develop
potentially life-threatening complications if the condition is not treated. The infected tissues may develop
large collections of pus (abscesses) that can rupture
into the patient’s airway, or the infection may spread
to the tissues surrounding the heart. In extreme cases
the empyema may spread to the brain by means of
bacteria carried in the bloodstream.
In pelvic empyema, the infection produces large
amounts of thick, foul-smelling pus that is rapidly
replaced even after drainage. Empyema of the gallbladder is marked by intense pain on the upper right
side of the abdomen, high fever, and rigidity of the
muscles over the infected area.

Diagnosis
Causes and symptoms
Empyema thoracis can be caused by a number of
different organisms, including bacteria, fungi, and amebas, in connection with pneumonia, chest wounds, chest
surgery, lung abscesses, or a ruptured esophagus. The
infective organism can get into the pleural cavity either
GALE ENCYCLOPEDIA OF MEDICINE

A physician may consider the possibility of
empyema thoracis in patients with pneumonia or
other symptoms of lung infection. When listening to
sounds within the patient’s chest with a stethoscope,
the sounds of breathing will be partly muffled and
harder to hear in the patients with empyema. The
1307

Empyema

PERIODICALS

Empyema

area of the chest over the infection will sound dull
when tapped or thumped (percussed). On an x ray,
empyema thoracis will appear as a cloudy or opaque
area. The amount of fluid present in the pleural cavity
can be estimated using an ultrasound imaging procedure. The diagnosis of empyema, however, has to be
confirmed with laboratory tests because its symptoms
can be caused by other disease conditions.
The diagnosis of empyema is usually confirmed by
analyzing a sample of fluid taken from the pleural
cavity. The sample is obtained by a procedure called
thoracentesis. In this procedure, the patient is given a
local anesthetic, a needle is inserted into the pleural
cavity through the back between the ribs on the
infected side, and a sample of fluid is withdrawn. If
the patient has empyema, there will be a very high level
of one particular kind of immune cell (white blood
cells), a high level of protein, and a very low level of
blood sugar. The fluid can also be tested for the specific disease organism by staining or tissue cultures. In
some cases, the color, smell, or consistency of the
tissue fluid also helps to confirm the diagnosis.

Treatment
Empyema is treated using a combination of
medications and surgical techniques. Treatment with
medication involves intravenously administering a
two-week course of antibiotics. It is important to give
antibiotics as soon as possible to prevent first-stage
empyema from progressing to its later stages. The
antibiotics most commonly used are penicillin and
vancomycin. Patients experiencing difficulty breathing are also given oxygen therapy.
Surgical treatment of empyema has two goals:
drainage of the infected fluid and closing up of the
space left in the pleural cavity. If the infection is still in
its early stages, the fluid can be drained by thoracentesis. In second-stage empyema, the surgeon will insert
a chest tube in the patient’s rib cage or remove part of
a rib (rib resection) in order to drain the fluid. In thirdstage empyema, the surgeon may cut or peel away the
thick fibrous layer coating the lung. This procedure is
called decortication. When the fibrous covering is
removed, the lung will expand to fill the space in the
chest cavity. The doctor can use video-assisted thoracic surgery (VATS) techniques to position the chest
tube or to perform a limited decortication. The VATS
technique allows a physician to see within the body
during certain surgical procedures. Empyema of the
gallbladder is a serious condition that is treated with
intravenous antibiotics and surgical removal of the
gallbladder.
1308

KEY TERMS
Abscess—An area of inflamed and injured body
tissue that fills with pus.
Decortication—Surgical removal of the fibrous
peel that covers the lungs in third-stage empyema.
Empyema—The collection of pus in a body cavity,
particularly the lung or pleural cavity.
Fibrin—A fibrous blood protein vital to coagulation
and blood clot formation.
Percussion—A diagnostic technique in which the
back, chest, or abdomen is tapped to determine
whether body cavities contain abnormal fluid.
Pleural cavity—The space surrounding the lungs,
including the membranes covering the lungs and
lining the inside of the chest wall.
Pneumonia—Inflammation of the lungs usually
caused by a virus, bacteria, or other organism.
Resection—The surgical removal of part of an
organ or body structure, as in rib resection.
Suppurate—To produce or discharge pus.
Thoracentesis—A procedure in which fluid is withdrawn from the pleural cavity through a needle
inserted between the ribs. The fluid may be withdrawn either for diagnostic tests or to drain the
cavity.
Video-assisted thoracic surgery (VATS)—A technique used to aid in the placement of chest tubes or
when performing decortications when treating
advanced empyema.

Prognosis
The prognosis for recovery is generally good,
except in those cases with complications, such as a
brain abscess or blood poisoning, or cases caused by
certain types of streptococci.
Resources
BOOKS

Stauffer, John L. ‘‘Lung.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange,1997.

Rebecca J. Frey, PhD

Enalapril see Angiotensin-converting
enzyme inhibitors
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Encephalitis is an inflammation of the brain,
usually caused by a direct viral infection or a hypersensitivity reaction to a virus or foreign protein. Brain
inflammation caused by a bacterial infection is sometimes called cerebritis. When both the brain and spinal
cord are involved, the disorder is called encephalomyelitis. An inflammation of the brain’s covering, or
meninges, is called meningitis.

Description
Encephalitis is an inflammation of the brain. The
inflammation is a reaction of the body’s immune system to infection or invasion. During the inflammation,
the brain’s tissues become swollen. The combination
of the infection and the immune reaction to it can
cause headache and a fever, as well as more severe
symptoms in some cases.
Approximately 2,000 cases of encephalitis are
reported to the Centers for Disease Control in Atlanta,
GA each year. The viruses causing primary encephalitis
can be epidemic or sporadic. The polio virus is an epidemic cause. Arthropod-borne viral encephalitis is
responsible for most epidemic viral encephalitis. The
viruses live in animal hosts and mosquitos that transmit
the disease. The most common form of non-epidemic or
sporadic encephalitis is caused by the herpes simplex
virus, type 1 (HSV-1) and has a high rate of death.
Mumps is another example of a sporadic cause.

Causes and symptoms
Causes
There are more than a dozen viruses that can cause
encephalitis, spread by either human-to human contact
or by animal bites. Encephalitis may occur with several
common viral infections of childhood. Viruses and
viral diseases that may cause encephalitis include:


chickenpox



measles



mumps



Epstein-Barr virus (EBV)



cytomegalovirus infection



HIV



herpes simplex



herpes zoster (shingles)

GALE ENCYCLOPEDIA OF MEDICINE

herpes B



polio



rabies



mosquito-borne viruses (arboviruses)

Encephalitis

I Encephalitis



Primary encephalitis is caused by direct infection
by the virus, while secondary encephalitis is due to a
post-infectious immune reaction to viral infection elsewhere in the body. Secondary encephalitis may occur
with measles, chickenpox, mumps, rubella, and EBV.
In secondary encephalitis, symptoms usually begin
five to 10 days after the onset of the disease itself and
are related to the breakdown of the myelin sheath that
covers nerve fibers.
In rare cases, encephalitis may follow vaccination
against some of the viral diseases listed above.
Creutzfeldt-Jakob disease, a very rare brain disorder
caused by an infectious particle called a prion, may
also cause encephalitis.
Mosquitoes spread viruses responsible for equine
encephalitis (eastern and western types), St. Louis encephalitis, California encephalitis, and Japanese encephalitis. Lyme disease, spread by ticks, can cause
encephalitis, as can Colorado tick fever. Rabies is most
often spread by animal bites from dogs, cats, mice, raccoons, squirrels, and bats and may cause encephalitis.
Equine encephalitis is carried by mosquitoes that
do not normally bite humans but do bite horses and
birds. It is occasionally picked up from these animals
by mosquitoes that do bite humans. Japanese encephalitis and St. Louis encephalitis are also carried by
mosquitoes. The risk of contracting a mosquitoborne virus is greatest in mid- to late summer, when
mosquitoes are most active, in those rural areas where
these viruses are known to exist. Eastern equine encephalitis occurs in eastern and southeastern United
States; western equine and California encephalitis
occur throughout the West; and St. Louis encephalitis
occurs throughout the country. Japanese encephalitis
does not occur in the United States, but is found
throughout much of Asia. The viruses responsible
for these diseases are classified as arbovirus and these
diseases are collectively called arbovirus encephalitis.
Herpes simplex encephalitis, the most common
form of sporadic encephalitis in western countries, is
a disease with significantly high mortality. It occurs in
children and adults and both sides of the brain are
affected. It is theorized that brain infection is caused
by the virus moving from a peripheral location to the
brain via two nerves, the olfactory and the trigeminal
(largest nerves in the skull).
1309

Encephalitis

Herpes simplex encephalitis is responsible for
10% of all encephalitis cases and is the main cause of
sporadic, fatal encephalitis. In untreated patients, the
rate of death is 70% while the mortality is 15–20% in
patients who have been treated with acyclovir. The
symptoms of herpes simplex encephalitis are fever,
rapidly disintegrating mental state, headache, and
behavioral changes.
Symptoms
The symptoms of encephalitis range from very
mild to very severe and may include:


headache



fever



lethargy (sleepiness, decreased alertness, and fatigue)



malaise



nausea and vomiting



visual disturbances



tremor



decreased consciousness (drowsiness, confusion,
delirium, and unconsciousness)



stiff neck



seizures

Symptoms may progress rapidly, changing from
mild to severe within several days or even several
hours.

Diagnosis
Diagnosis of encephalitis includes careful questioning to determine possible exposure to viral
sources. Tests that can help confirm the diagnosis
and rule out other disorders include:


Blood tests. These are to detect antibodies to viral
antigens, and foreign proteins.



Cerebrospinal fluid analysis (spinal tap). This detects
viral antigens, and provides culture specimens for the
virus or bacteria that may be present in the cerebrospinal fluid.



Electroencephalogram (EEG).



CT and MRI scans.

A brain biopsy (surgical gathering of a small tissue
sample) may be recommended in some cases where
treatment to date has been ineffective and the cause
of the encephalitis is unclear. Definite diagnosis by
biopsy may allow specific treatment that would otherwise be too risky.
1310

Treatment
Choice of treatment for encephalitis will depend
on the cause. Bacterial encephalitis is treated with
antibiotics. Viral encephalitis is usually treated with
antiviral drugs including acyclovir, ganciclovir, foscarnet, ribovarin, and AZT. Viruses that respond to
acyclovir include herpes simplex, the most common
cause of sporadic (non-epidemic) encephalitis in the
United States.
The symptoms of encephalitis may be treated with
a number of different drugs. Corticosteroids, including
prednisone and dexamethasone, are sometimes prescribed to reduce inflammation and brain swelling.
Anticonvulsant drugs, including dilantin and phenytoin, are used to control seizures. Fever may be
reduced with acetaminophen or other fever-reducing
drugs.
A person with encephalitis must be monitored
carefully, since symptoms may change rapidly. Blood
tests may be required regularly to track levels of fluids
and salts in the blood.

Prognosis
Encephalitis symptoms may last several weeks.
Most cases of encephalitis are mild, and recovery is
usually quick. Mild encephalitis usually leaves no residual neurological problems. Overall, approximately
10% of those with encephalitis die from their infections or complications such as secondary infection.
Some forms of encephalitis have more severe courses,
including herpes encephalitis, in which mortality is
15–20% with treatment, and 70–80% without.
Antiviral treatment is ineffective for eastern equine
encephalitis, and mortality is approximately 30%.
Permanent neurological consequences may follow
recovery in some cases. Consequences may include
personality changes, memory loss, language difficulties, seizures, and partial paralysis.

Prevention
Because encephalitis is due to infection, it may be
prevented by avoiding the infection. Minimizing contact with others who have any of the viral illness listed
above may reduce the chances of becoming infected.
Most infections are spread by hand-to-hand or handto-mouth contact; frequent hand washing may reduce
the likelihood of infection if contact cannot be avoided.
Mosquito-borne viruses may be avoided by preventing mosquito bites. Mosquitoes are most active at
dawn and dusk, and are most common in moist areas
GALE ENCYCLOPEDIA OF MEDICINE

Encopresis

I Encopresis

KEY TERMS
Cerebrospinal fluid analysis—A analysis that is
important in diagnosing diseases of the central nervous system. The fluid within the spine will indicate
the presence of viruses, bacteria, and blood.
Infections such as encephalitis will be indicated by
an increase of cell count and total protein in the fluid.
Computerized tomography (CT) Scan—A test to
examine organs within the body and detect evidence
of tumors, blood clots, and accumulation of fluids.
Electroencephalagram (EEG)—A chart of the brain
waves picked up by the electrodes placed on the
scalp. Changes in brain wave activity can be an
indication of nervous system disorders.
Inflammation—A response from the immune system to an injury. The signs are redness, heat, swelling, and pain.
Magnetic Resonance Imaging (MRI)—MRI is diagnostic radiography using electromagnetic energy to
create an image of the central nervous system
(CNS), blood system, and musculoskeletal system.
Vaccine—A prepartation containing killed or weakened microorganisms used to build immunity
against infection from that microorganism.
Virus—A very small organism that can only live
within a cell. They are unable to reproduce outside
that cell.

with standing water. Minimizing exposed skin and use
of mosquito repellents on other areas can reduce the
chances of being bitten.
Vaccines are available against some viruses,
including polio, herpes B, Japanese encephalitis, and
equine encephalitis. Rabies vaccine is available for
animals; it is also given to people after exposure.
Japanese encephalitis vaccine is recommended for
those traveling to Asia and staying in affected rural
areas during transmission season.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Richard Robinson

Encephalocele see Congenital brain defects
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Encopresis is repeatedly having bowel movements
in places other than the toilet after the age when bowel
control can normally be expected.

Description
Most children have established bowel control by
the time they are four years old. After that age, when
they repeatedly have bowel movements in inappropriate places, they may have encopresis. In the United
States, encopresis affects 1–2% of children under age
10. About 80% of these are boys.
Encopresis can be either involuntary or voluntary.
Involuntary encopresis is related to constipation, passing hard painful feces, and difficult bowel movements. Often children with involuntary encopresis
stain their underpants with liquid feces. They are
usually unaware that this has happened. Voluntary
encopresis is much less common and is associated
with behavioral or psychological problems. Both
types of encopresis occur most often when the child
is awake, rather than at night.

Causes and symptoms
Although a few children experience encopresis
because of malformations of the lower bowel and
anus or irritable bowel disease, most have no physical problems to explain this disorder. Constipation is
present in about 80% of children who experience
involuntary encopresis. As feces moves through the
large intestine, water is removed. The longer the
feces stays in the large intestine, the more water is
removed, and the harder the feces becomes. The
result can be hard or painful bowel movements. In
response, children may start to hold back when they
feel the urge to eliminate in order to avoid pain. This
starts a cycle of constipation that results in retentive
encopresis.
Once elimination is avoided, the bowel becomes
full of hard feces. This stretches the large intestine.
Eventually the intestine becomes so stretched that
liquid feces backed up behind the blockage is able to
leak around the hard feces. Children with this type of
encopresis do not feel the urge to have a bowel movement and are often surprised when their pants are
stained with foul smelling liquid feces. This leakage
of feces is called overflow incontinence. Parents sometimes mistake this soiling for diarrhea, because the
1311

Encopresis

feces expelled is liquid. Every so often, children with
involuntary encopresis may pass large stools, sometimes with volumes big enough to clog the toilet, but
the relief this brings is temporary.
Although about 95% of encopresis is involuntary,
some children intentionally withhold bowel movements. The American Psychiatric Association (APA)
recognizes voluntary encopresis without constipation
as a psychological disorder. This disorder is said to
occur when a child who has control over his bowel
movements chooses to have them in an inappropriate
place. The feces is a normal consistency, not hard.
Sometimes it is smeared in an obvious place, but it
may also be hidden from adults.
Voluntary encopresis may result from a power
struggle between caregivers and the child during toilet
training, or the child may have developed an unusual
fear of the toilet. It is also associated with oppositional
defiant disorder (ODD), conduct disorder, sexual abuse,
and high levels of psychological stress. For example,
children who were separated from their parents during
World War II were reported to have a high rate of
encopresis. However, parents and caregivers should be
aware that very few children soil intentionally and
most do not have a behavioral or psychological problem and should not be punished for their soiling
accidents.

Diagnosis
Diagnosis is based primarily on the child’s history
of inappropriate bowel movements. Physical examinations are almost always normal, except for a mass of
hard feces blocking the lower intestine. Other physical
causes of soiling, such as illness, reaction to medication, food allergies, and physical disabilities, may also
be ruled out through history and a physical examination. In addition, to be diagnosed with encopresis the
child must be old enough to establish regular bowel
control—usually chronologically and developmentally at least four years of age.

Treatment
The goal of treatment is to establish regular, soft,
pain free bowel movements in the toilet. First the
physician tries to determine the cause of encopresis,
whether physical or psychological. Regardless of the
cause, the bowel must be emptied of hard, impacted
feces This can be done using an enema, laxatives,
and/or stool softeners such as mineral oil. Enemas
and laxatives should be used only at a doctor’s
recommendation.
1312

KEY TERMS
Feces—Waste products eliminated from the large
intestine; excrement.
Incontinence—The inability to control the release
of urine or feces.
Laxative—Material that encourages a bowel
movement.
Stools—feces, bowel movements.

Next, the child is given stool softeners to keep feces
soft and to give the stretched intestine time to shrink
back to its normal size. This shrinking process may
take several months, during which time stool softeners
may need to be used regularly. Children also need two
or three regularly scheduled toilet sits daily in an effort
to establish consistent bowel habits. These toilet sits are
often more effective if done after meals. Maintaining
soft, easy-to-pass stools is also important if the child is
afraid of the toilet because of past painful bowel movements. A child psychologist or psychiatrist can suggest
treatment for the rare child with serious behavioral
problems such as smearing or hiding feces.

Alternative treatment
Many herbal stool softeners and laxatives are
available as both tablets and liquids. Psyllium, the
seed of several plants of the genus Plantago is one of
the most effective. Other natural remedies for constipation include castor seed oil (Ricinus communis),
senna (Cassia senna or Senna alexandrina), and dong
quai Angelica polymorpha or Angelica sinensis).

Prognosis
For almost all children, once constipation is controlled, the problem of soiling disappears. This make
take several months, and relapses may occur, but with
effective prevention strategies, encopresis can be eliminated. Children who are in a power struggle over
toileting usually outgrow their desire to have bowel
movements in inappropriate places. The prognosis for
children with serious behavioral and psychological
problems that result in smearing or hiding feces
depends largely on resolving the underlying problems.

Prevention
The best way to prevent encopresis is to prevent
constipation. Methods of preventing constipation
include:
GALE ENCYCLOPEDIA OF MEDICINE

increasing the amount of liquids, especially water,
the child drinks



adding high fiber foods to the diet (e.g. dried beans,
fresh fruits and vegetables, whole wheat bread and
pasta, popcorn)



establishing regular bowel habits



limiting the child’s intake of dairy products (e.g.
milk, cheese, yogurt, ice cream) that promote
constipation.



treating constipation promptly with stool softeners,
so that it does not become worse.

Resources

artery. An endarterectomy is performed to treat cerebrovascular disease in which there is a serious reduction of blood supply to the brain (carotid
endarterectomy), or to treat peripheral vascular disease
(impaired blood supply to the legs).
Endarterectomy is most often performed on one
of the two main arteries in the neck (the carotids)
opening the narrowed arteries leading to the brain.
When performed by an experienced surgeon, the practice is extremely effective, reducing the risk of stroke
by up to 70%. Recent studies indicate it is effective in
preventing stroke, even among those patients who had
no warning signs except narrowed arteries detected by
their doctors on a routine exam.

BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders, 4th ed. text revision.
Washington D.C.: American Psychiatric Association,
2000.
PERIODICALS

Kuhn, Brett R., Bethany A. Marcus, and Sheryl L. Pitner.
‘‘Treatment Guidelines for Primary Nonretentive
Encopresis and Stool Toileting Refusal.’’ American
Family Physician, 59, no. 8 (15 April 1999) 2171-2183.
[cited 16 February 2005]. <http://www.aafp.org/afp/
2001101/1565.html>.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry, P.
O. Box 96106, Washington, D.C. 20090. 800-333-7636.
<www.aacap.org>.
OTHER

Borowitz, Stephen. Encopresis, 14 June 2004 [cited 20
February 2005]. <http://www.emedicine.com/ped/
topics670.html>.

Precautions
Before the surgery, a full medical exam is usually
done to assess any specific health problems, such as
diabetes, high blood pressure, heart disease, or stroke.
If possible, reversible health problems, such as cigarette smoking or being overweight, should be corrected.

Description
Carotid artery disease
Every person has four carotid arteries (the internal and external carotids on each side of the neck)
through which blood from the heart moves into the
brain. If one of these arteries becomes blocked by fat
and cholesterol, the patient may have a range of symptoms, including:


weakness in one arm, leg, half of the face, or one
entire side of the body



numbness or tingling



paralysis of an arm, leg, or face



slurred speech



dizziness



confusion, fainting, or coma



stroke

Tish Davidson, A.M.

I Endarterectomy
Definition
Endarterectomy is an operation to remove or
bypass the fatty deposits, or blockage, in an artery
narrowed by the buildup of fatty tissue
(atherosclerosis).

Purpose
Removing the fatty deposits restores normal
blood flow to the part of the body supplied by the
GALE ENCYCLOPEDIA OF MEDICINE

Removing this fatty buildup, or bypassing a
blocked segment, may restore blood flow to the
brain, eliminate or decrease the symptoms, and lessen
the risk of a stroke.
Peripheral vascular disease
When the blood vessels in the legs (and sometimes
the arms) become narrowed, this can restrict blood
flow and cause pain in the affected area. In severe
cases, the tissue may die, requiring amputation.
1313

Endarterectomy



Endarterectomy

the body, arterial reconstructive surgery may be
required.
The total cost of an endarterectomy, including
diagnostic tests, surgery, hospitalization, and followup care, will vary according to hospital, doctor, and
area of the country where the operation is performed,
but a patient can expect to pay in the range of $15,000.
Patients who are very young, very old, or very ill, or
who need more extensive surgery, may require more
expensive treatment.

Preparation
Before surgery, the doctor pinpoints the location
of the narrowed artery with an x-ray procedure called
angiography. For surgery to be effective, the degree of
narrowing should be at least 70%, but it should not be
total. Patients undergoing angiography are given a
local anesthetic, but the endarterectomy itself requires
the use of a general anesthesia.
In this procedure, surgeons are removing plaque from the
carotid artery. (Custom Medical Stock Photo. Reproduced by
permission.)

The narrowing is usually caused by buildup of
fatty plaques in the vessels, often as the result of
smoking, high blood pressure, or poorly-controlled
diabetes mellitus. The vessels usually narrow slowly,
but it’s possible for a blood clot to form quickly,
causing sudden severe pain in the affected leg or arm.
Procedure
Endarterectomy is a delicate operation that may
require several hours. The surgeon begins by making
an incision over the blocked artery and inserting a tube
above and below the blockage to redirect the blood
flow while the artery is opened.
Next, the surgeon removes the fat and cholesterol
buildup, along with any blood clots that have formed,
with a blunt dissecting instrument. Then the surgeon
bathes the clean wall in salt solution combined with
heparin, an anticoagulant. Then the surgeon stitches
the artery just enough so that the bypass shunt tube
can be removed, and then he/she stitches the artery
completely closed. After checking to make sure no
blood is leaking, the surgeon next closes the skin incision with stitches.
The operation should improve symptoms,
although its long-term effects may be more limited,
since arterial narrowing is rarely confined to one area
of one artery. If narrowing is a problem throughout
1314

Aftercare
After the surgery, the patient spends the first two
days lying flat in bed. Patients who have had carotid
endarterectomy should not bend the neck sharply during this time. Because the blood flow to the brain is
now greatly increased, patients may experience a brief
but severe headache, or lightheadedness. There may be
a slight loss of sensation in the skin, or maybe a droop
in the mouth, if any of the nerves in the neck were
lightly bruised during surgery. In time, this should
correct itself.

Risks
The amount of risk depends on the hospital, the
skill of the surgeon, and the severity of underlying disease. Patients who have just had an acute stroke are at
greatest risk. During carotid artery surgery, blood flow
is interrupted through the artery, so that paralysis and
other stroke symptoms may occur. These may resolve
after surgery, or may result in permanent stroke.
Paralysis is usually one-sided; other stroke symptoms
may include loss of half the field of vision, loss of
sensation, double vision, speech problems, and personality changes. Risks of endarterectomy to treat either
carotid artery or peripheral vascular disease include:


reactions to anesthesia



bleeding



infection



blood clots
GALE ENCYCLOPEDIA OF MEDICINE

Endarterectomy

Plaque

Carotid
artery

Clamp

Plaque is removed from the carotid artery by clamping the artery, cutting the plaque out, and closing the opening back up.
(Illustration by Argosy Inc.)

KEY TERMS
Carotid arteries—The four principal arteries of the
neck and head. There are two common carotid
arteries, each of which divides into the two main
branches (internal and external).
Diabetes mellitus—A disorder in which the pancreas doesn’t produce enough (or any) insulin. As a
result, the blood levels of sugar become very high.
Among other things, diabetes can lead to the breakdown of small blood vessels and a high risk of
atherosclerosis and high blood pressure.
Stroke—Damage to the part of the brain caused by
an interruption of the blood supply. In some cases,
small pieces of plaque in the carotid artery may
break loose and block an artery in the brain. A
narrowed carotid artery also can be the source of
blood clots travelling to the brain, or the artery can
become completely clogged, blocking all blood
flow to the brain.

GALE ENCYCLOPEDIA OF MEDICINE

Normal results
The results after successful surgery are usually
striking. The newly opened artery should help to
restore normal blood flow. In carotid endarterectomy,
surgery should prevent the risk of brain damage and
stroke. However, the buildup of fat and cholesterol
usually affects all arteries, not just the one that was
operated on. Affected arteries in other parts of the
body may be equally clogged and potentially dangerous. Even arteries that were operated electively will
likely begin to clog up again after the surgery.
For this reason, lifestyle changes (no smoking,
low fat, low cholesterol diet) are important, especially
if diet and lifestyle contributed to the development of
the problem in the first place.
Resources
PERIODICALS

‘‘Better Blood Flow: Surgery May Strike Down Stroke
Risk.’’Prevention 47 (February 1, 1995): 50-52.
1315

Endocarditis

ORGANIZATIONS

National Institute of Neurological Disorders and Stroke. PO
Box 5801, Bethesda, MD 20824. (800) 352-9424.
<http://www.ninds.nih.gov/index.htm>.
National Institute of Neurological Disorders at the
Neurology Institute. PO Box 5801, Bethesda, MD
20824.

Carol A. Turkington

Endemic syphilis see Bejel
Endocardial resection see Myocardial
resection

I Endocarditis
Definition
The endocardium is the inner lining of the heart
muscle, which also covers the heart valves. When the
endocardium becomes damaged, bacteria from the
blood stream can become lodged on the heart valves
or heart lining. The resulting infection is known as
endocarditis.

Description
The endocardium lines all four chambers of the
heart–two at the top (the right and left atria) and two
at the bottom (the right and left ventricles)–through
which blood passes as the heart beats. It also covers
the four valves (the tricuspid valve, the pulmonary
valve, the mitral valve, and the aortic valve), which
normally open and close to allow the blood to flow in
only one direction through the heart during each
contraction.
For the heart to pump blood efficiently, the four
chambers must contract and relax, and the four valves
must open and close, in a well coordinated fashion. By
damaging the valves or the walls of the heart chambers, endocarditis can interfere with the ability of the
heart to do its job.
Endocarditis rarely occurs in people with healthy,
normal hearts. Rather, it most commonly occurs when
there is damage to the endocardium. The endocardium
may be affected by a congenital heart defect, such as
mitral valve prolapse, in which blood leaks through a
poorly functioning mitral valve back into the heart. It
may also be damaged by a prior scarring of the heart
muscle, such as rheumatic fever, or replacement of a
heart valve. Any of these conditions can damage the
1316

A close-up view of an infected artificial heart valve showing
bacterial endocarditis (the granulated tissue at center of
image). When infection occurs early after surgery, it is likely
that organisms have gained entry during the operative period. This type of infection is usually caused by Staphylococcus
epidermidis and S. aureus and is treated with antibiotic drugs.
(Photograph by Dr. E. Walker, Photo Researchers, Inc.
Reproduced by permission.)

endocardium and make it more susceptible to
infection.
Bacteria can get into the blood stream (a condition
known as bacteremia) in a number of different ways: It
may spread from a localized infection such as a urinary
tract infection, pneumonia, or skin infection or get into
the blood stream as a result of certain medical conditions, such as severe periodontal disease, colon cancer,
or inflammatory bowel disease. It can enter the blood
stream during minor procedures, such as periodontal
surgery, tooth extractions, teeth cleaning, tonsil
removal, prostate removal, or endoscopic examination.
It can also be introduced through in-dwelling catheters,
which are used for intravenous medications, intravenous feeding, or dialysis. In people who use intravenous
drugs, the bacteria can enter the blood stream through
unsterilized, contaminated needles and syringes.
(People who are prone to endocarditis generally need
to take prescribed antibiotics before certain surgical or
dental procedures to help prevent this infection.)
If not discovered and treated, infective endocarditis can permanently damage the heart muscle, especially the valves. For the heart to work properly, all
four valves must be functioning well, opening at the
right time to let blood flow in the right direction and
closing at the right time to keep the blood from flowing in the wrong direction. If the valve is damaged, this
may allow blood to flow backward–a condition
known as regurgitation. As a result of a poorly functioning valve, the heart muscle has to work harder to
pump blood and may become weakened, leading to
GALE ENCYCLOPEDIA OF MEDICINE

heart failure. Heart failure is a chronic condition in
which the heart is unable to pump blood well enough
to supply blood adequately to the body.
Another danger associated with endocarditis is
that the vegetation formed by bacteria colonizing on
heart valves may break off, forming emboli. These
emboli may travel through the circulation and become
lodged in blood vessels. By blocking the flow of blood,
emboli can starve various tissues of nutrients and
oxygen, damaging them. For instance, an embolus
lodged in the blood vessels of the lungs may cause
pneumonia-like symptoms. An embolus may also
affect the brain, damaging nerve tissue, or the kidneys,
causing kidney disease. Emboli may also weaken the
tiny blood vessels called capillaries, causing hemorrhages (leaking blood vessels) throughout the body.

Causes and symptoms
Most cases of infective endocarditis occur in
people between the ages of 15 and 60, with a median age at onset of about 50 years. Men are
affected about twice as often as women are. Other
factors that put people at increased risk for endocarditis are congenital heart problems, heart surgery, previous episodes of endocarditis, and
intravenous drug use.
While there is no single specific symptom of
endocarditis, a number of symptoms may be present. The most common symptom is a mild fever,
which rarely goes above 1028F (38.98C). Other
symptoms include chills, weakness, cough, trouble
breathing, headaches, aching joints, and loss of
appetite.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Doctors begin the diagnosis by taking a history, asking the patient about the symptoms mentioned above. During a physical examination, the
doctor may also uncover signs such as fever, an
enlarged spleen, signs of kidney disease, or hemorrhaging. Listening to the patient’s chest with a
stethoscope, the doctor may also hear a heart murmur. A heart murmur may indicate abnormal flow
of blood through one of the heart chambers or
valves.
Doctors take a sample of the patient’s blood to
test it for bacteria and other microorganisms that
may be causing the infection. They usually also use
a test called echocardiography, which uses ultrasound
waves to make images of the heart, to check for
abnormalities in the structure of the heart wall or
valves. One of the tell-tale signs they look for in
echocardiography is vegetation, the abnormal
growth of tissue around a valve composed of blood
platelets, bacteria, and a clotting protein called
fibrin. Another tell-tale sign is regurgitation, or the
backward flow of blood, through one of the heart
valves. A normal echocardiogram does not exclude
the possibility of endocarditis, but an abnormal
echocardiogram can confirm its presence. If an echocardiogram cannot be done or its results are inconclusive, a modified technique called transesophageal
echocardiography
is
sometimes
performed.
Transesophageal echocardiography involves passing
an ultrasound device into the esophagus to get a
clearer image of the heart.
1317

Endocarditis

This echocardiogram shows an aortic regurgitation due to
endocarditis, an infection of the lining membrane of the cardiac chambers. (Custom Medical Stock Photo. Reproduced by
permission.)

Emboli may also cause a variety of symptoms,
depending on their location. Emboli throughout the
body may cause Osler’s nodes, small, reddish, painful
bumps most commonly found on the inside of fingers
and toes. Emboli may also cause petechiae, tiny purple or red spots on the skin, resulting from hemorrhages under the skin’s surface. Tiny hemorrhages
resembling splinters may also appear under the fingernails or toenails. If emboli become lodged in the
blood vessels of the lungs, they may cause coughing
or shortness of breath. Emboli lodged in the brain
may cause symptoms of a mini-stroke, such as numbness, weakness, or paralysis on one side of the body
or sudden vision loss or double vision. Emboli may
also damage the kidneys, causing blood to appear in
the urine. Sometimes the capillaries on the surface of
the spleen rupture, causing the spleen to become
enlarged and tender to the touch. Anyone experiencing any of these symptoms should seek medical help
immediately.

Endocarditis

KEY TERMS
Aortic valve—The valve between the left ventricle
of the heart and the aorta.
Bacteremia—An infection caused by bacteria in
the blood.
Congestive heart failure—A condition in which the
heart muscle cannot pump blood as efficiently as it
should.
Echocardiography—A diagnostic test using
reflected sound waves to study the structure and
motion of the heart muscle.
Embolus—A bit of foreign material, such as gas, a
piece of tissue, or tiny clot, that travels in the
circulation until it becomes lodged in a blood
vessel.
Endocardium—The inner wall of the heart muscle,
which also covers the heart valves.
Mitral valve—The valve between the left atrium
and the left ventricle of the heart.
Osler’s nodes—Small, raised, reddish, tender areas
associated with endocarditis, commonly found
inside the fingers or toes.
Petechiae—Tiny purple or red spots on the skin
associated with endocarditis, resulting from hemorrhages under the skin’s surface.
Pulmonary valve—The valve between the right
ventricle of the heart and the pulmonary artery.
Transducer—A device that converts electrical signals into ultrasound waves and ultrasound waves
back into electrical impulses.
Transesophageal echocardiography—A diagnostic
test using an ultrasound device, passed into the
esophagus of the patient, to create a clear image
of the heart muscle.
Tricuspid valve—The valve between the right
atrium and the right ventricle of the heart.
Vegetation—An abnormal growth of tissue around
a valve, composed of blood platelets, bacteria, and
a protein involved in clotting.

the results of the blood culture become available, the
doctor can adjust the medications, using specific antibiotics known to be effective against the specific
microorganism involved.
Unfortunately, in recent years, the treatment of
endocarditis has become more complicated as a result
of antibiotic resistance. Over the past few years, especially as antibiotics have been overprescribed, more
and more strains of bacteria have become increasingly
resistant to a wider range of antibiotics. For this reason, doctors may need to try a few different types of
antibiotics–or even a combination of antibiotics–to
successfully treat the infection. Antibiotics are usually
given for about one month, but may need to be given
for an even longer period of time if the infection is
resistant to treatment.
Once the fever and the worst of the symptoms
have gone away, the patient may be able to continue
antibiotic therapy at home. During this time, the
patient should make regular visits to the health care
team for further testing and physical examination to
make sure that the antibiotic therapy is working, that
it is not causing adverse side effects, and that there are
no complications such as emboli or heart failure. The
patient should alert the health-care team to any symptoms that could indicate serious complications: For
instance, trouble breathing or swelling in the legs
could indicate congestive heart failure. Headache,
joint pain, blood in the urine, or stroke symptoms
could indicate an embolus, and fever and chills could
indicate that the treatment is not working and the
infection is worsening. Finally, diarrhea, rash, itching,
or joint pain may suggest a bad reaction to the antibiotics. Anyone experiencing any of these symptoms
should alert the health care team immediately.
In some cases, surgery may be needed. These
include cases of congestive heart failure, recurring
emboli, infection that doesn’t respond to treatment,
poorly functioning heart valves, and endocarditis
involving prosthetic (artificial) valves. The most common surgical treatment involves cutting away (debriding) damaged tissue and replacing the damaged valve.

Prognosis
Treatment
When doctors suspect infective endocarditis, they
will admit the patient to a hospital and begin treating
the infection before they even have the results of the
blood culture. Their choice of antibiotics depends on
what the most likely infecting microorganism is. Once
1318

If left untreated, infective endocarditis continues
to progress and is always fatal. However, if it is diagnosed and properly treated within the first six weeks of
infection, the infection can be completely cured in
about 90% of the cases. The prognosis depends on a
number of factors, such as the patient’s age and overall
physical condition, the severity of the diseases
involved, the exact site of the infection, how
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Some people are especially prone to endocarditis.
These include people with past episodes of endocarditis, those with congenital heart problems or heart
damage from rheumatic fever, and those with artificial
heart valves. Intravenous drug users are also at
increased risk. Anyone who falls into a high-risk category should alert his or her health-care professionals
before undergoing any surgical or dental procedures.
High-risk patients must be treated in advance with
antibiotics before these procedures to minimize the
risk of infection.
Resources
BOOKS

Zaret, Barry L., et al., editors. The Patient’s Guide to Medical
Tests. Boston: Houghton Mifflin, 1997.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Robert Scott Dinsmoor

Endocrine pancreatic cancer see Pancreatic
cancer, endocrine

I Endometrial biopsy
Definition
Endometrial biopsy is a procedure in which a
sample of the endometrium (tissue lining the inside
of the uterus) is removed for microscopic examination.

Purpose
The test is most often performed to find out the
cause of abnormal uterine bleeding. Abnormal bleeding includes bleeding between menstrual periods,
excessive bleeding during a menstrual period, or bleeding after menopause. Since abnormal uterine bleeding
can indicate cancer, an endometrial biopsy is done to
GALE ENCYCLOPEDIA OF MEDICINE

rule out endometrial cancer or hyperplasia (a potentially precancerous condition).
Endometrial biopsies are also done as a screening
test for endometrial cancer in postmenopausal women
on hormone replacement therapy. Hormone replacement therapy usually requires a woman to take estrogen and progesterone. An endometrial biopsy is
particularly useful in cases where postmenopausal
women take estrogen, but cannot take progesterone.
Estrogen in the system without the balancing effect of
progesterone has been linked to an increased risk of
endometrial cancer.
An endometrial biopsy can also be used as part of
an infertility exam to rule out problems with the development of the endometrium. This condition is called
luteal phase defect and can cause the endometrium to
not support a pregnancy. An endometrial biopsy can
also be used to evaluate the problem of repeated early
miscarriages.

Precautions
If the endometrial biopsy is being done to investigate why a woman is unable to get pregnant, the test
must be performed at a specific time during the menstrual cycle. Since the test evaluates whether the endometrium is developed adequately to support
implantation and growth of a fertilized egg, it is critical to perform the test approximately three days
before the expected menstrual period.

Description
The test is performed by a doctor who specializes
in women’s reproductive health (an obstetrician/gynecologist). The test is performed either in the doctor’s
office or in a local hospital. The patient may be asked
to take pain medication (like Motrin or Aleve) an hour
or so before the procedure. A local anesthetic may be
injected into the cervix in order to decrease pain and
discomfort during the procedure.
The woman will be asked to lie on her back with
knees apart and feet in stirrups. The doctor will first
conduct a thorough exam of the pelvic region, including the vulva (the external genitals), vagina, and
uterus. A speculum (an instrument that is used to
hold the walls of the vagina open) will be inserted
into the vagina. A small, hollow plastic tube is then
passed into the uterine cavity. A small piece of the
uterine lining is sucked out with a plunger that is
attached to the tube. Once the sample is obtained,
the instruments are removed. The sample is sent to
the laboratory for microscopic examination.
1319

Endometrial biopsy

vulnerable the microorganisms are to antibiotics, and
what kind of complications the endocarditis may be
causing.

Endometrial biopsy
A micrograph image of the internal human uterine wall depicting the mucosa, or endometrium. (Photograph by Professors
P.M. Motta and S. Makabe, Custom Medical Stock Photo. Reproduced by permission.)

The patient may experience some pain when the
cervix is grasped. The patient may also feel some
cramping, pressure, and discomfort when the instruments are inserted into the uterus and the tissue sample is collected.

Preparation
For the small number of endometrial biopsies that
are done as part of infertility testing, a pregnancy test
is also often performed before the procedure. Since the
biopsy is performed late in the menstrual cycle, it is
possible that the woman may be pregnant.

Aftercare
The biopsy may cause a small amount of bleeding
(spotting). The woman can resume normal activities
1320

right away. If cramping becomes severe, heavy bleeding occurs, or the woman develops a high temperature,
the doctor should be notified immediately.
If the test is being done to determine the cause of
infertility, the onset of the menstrual period following
the biopsy should be reported to the doctor. This will
allow the doctor to correctly predict if the endometrium has been developing at the expected rate.

Risks
The risks of an endometrial biopsy are very small.
There is a possibility that prolonged bleeding may
occur after the procedure. There is also a slight chance
of an infection. Very rarely, there are instances when
the uterus is pierced (perforated) or the cervix is torn
because of the biopsy.
GALE ENCYCLOPEDIA OF MEDICINE

Endometrial biopsy

Uterus

Vagina

Catheter

A catheter is inserted into the uterus to remove uterine cells for further examination. (Illustration by Argosy Inc.)

KEY TERMS
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.

are said to be ‘‘in-phase’’ because the tissue looks
appropriate and has developed normally for the late
phase of the menstrual cycle.

Abnormal results

Cervix—The opening of the uterus extending into
the vagina.
Endometrium—The layer lining the inner cavity of
the uterus; this layer changes daily throughout the
menstrual cycle.

If the endometrium is not developing at the appropriate rate, the results are said to be ‘‘out-of-phase’’ or
abnormal. The endometrium has not developed
appropriately and cannot support a pregnancy. This
condition is called luteal phase defect and may need to
be treated with progesterone.

Uterus—The hollow, muscular female organ that
supports the development and nourishment of the
unborn baby during pregnancy.

Abnormal appearance of the cells forming the
uterine tissue could also indicate uterine cancer, or
the presence of fibroids or polyps in the uterus.
Resources

Normal results
Most biopsies are done to rule out endometrial
cancer or endometrial hyperplasia. A normal result
shows no cancerous or precancerous cells. Normal
results also show that the uterine lining is changing
at the proper rate. If it is, then the results of the biopsy
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
Cancer Research Institute. 681 Fifth Ave., New York,
N.Y. 10022. (800) 992-2623. <http://
www.cancerresearch.org>.
1321

Endometrial cancer

Gynecologic Cancer Foundation. 401 North Michigan Ave.,
Chicago, IL 60611. (800) 444-4441.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Lata Cherath, PhD

The highest incidence of endometrial cancer in the
United States is in Caucasians, Hawaiians, Japanese,
and African Americans. American Indians, Koreans,
and Vietnamese have the lowest incidence. African
American and Hawaiian women are more likely to
be diagnosed with advanced cancer and, therefore,
have a higher risk of dying from the disease.

Causes and symptoms

I Endometrial cancer
Definition
Endometrial cancer develops when the cells that
make up the inner lining of the uterus (the endometrium) become abnormal and grow uncontrollably.

Description
Endometrial cancer (also called uterine cancer) is
the fourth most common type of cancer among
women and the most common gynecologic cancer.
Approximately 34,000 women are diagnosed with
endometrial cancer each year. In 1998, approximately
6,300 women died from this cancer. Although endometrial cancer generally occurs in women who have
gone through menopause and are 45 years of age or
older, 30% of the women with endometrial cancer are
younger than 40 years of age. The average age at
diagnosis is 60 years old.
The uterus, or womb, is the hollow female organ
that supports the development of the unborn baby
during pregnancy. The uterus has a thick muscular
wall and an inner lining called the endometrium. The
endometrium is very sensitive to hormones and it
changes daily during the menstrual cycle. The endometrium is designed to provide an ideal environment
for the fertilized egg to implant and begin to grow. If
pregnancy does not occur, the endometrium is shed
causing the menstrual period.
More than 95% of uterine cancers arise in the
endometrium. The most common type of uterine cancer is adenocarcinoma. It arises from an abnormal
multiplication of endometrial cells (atypical adenomatous hyperplasia) and is made up of mature, specialized cells (well-differentiated). Less commonly,
endometrial cancer arises without a preceding hyperplasia and is made up of poorly differentiated cells.
The more common of these types are the papillary
serous and clear cell carcinomas. Poorly differentiated
endometrial cancers are often associated with a less
promising prognosis.
1322

Although the exact cause of endometrial cancer is
unknown, it is clear that high levels of estrogen, when
not balanced by progesterone, can lead to abnormal
growth of the endometrium. Factors that increase a
woman’s risk of developing endometrial cancer are:


Age. The risk is considerably higher in women who
are over the age of 50 and have gone through
menopause.



Obesity. Being overweight is a very strong risk factor
for this cancer. Fatty tissue can change other normal
body chemicals into estrogen, which can promote
endometrial cancer.



Estrogen replacement therapy. Women receiving
estrogen supplements after menopause have a 12
times higher risk of getting endometrial cancer if
progesterone is not taken simultaneously.



Diabetes. Diabetics have twice the risk of getting this
cancer as nondiabetic women. It is not clear if this
risk is due to the fact that many diabetics are also
obese and hypertensive. One 1998 study found that
women who were obese and diabetic were three times
more likely to develop endometrial cancer than
women who were obese but nondiabetic. This study
also found that nonobese diabetics were not at risk of
developing endometrial cancer.



Hypertension. High blood pressure (or hypertension)
is also considered a risk factor for uterine cancer.



Irregular menstrual periods. During the menstrual
cycle, there is interaction between the hormones
estrogen and progesterone. Women who do not ovulate regularly are exposed to high estrogen levels for
longer periods of time. If a woman does not ovulate
regularly, this delicate balance is upset and may
increase her chances of getting uterine cancer.



Early first menstruation or late menopause. Having
the first period at a young age (the mean age of
menses is 12.16 years in African American girls and
12.88 years in caucasian girls) or going through
menopause at a late age (over age 51) seem to put
women at a slightly higher risk for developing endometrial cancer.
GALE ENCYCLOPEDIA OF MEDICINE

Tamoxifen. This drug, which is used to treat or prevent breast cancer, increases a woman’s chance of
developing endometrial cancer. Tamoxifen users
tend to have more advanced endometrial cancer
with an associated poorer survival rate than those
who do not take the drug. In many cases, however,
the value of tamoxifen for treating breast cancer and
for preventing the cancer from spreading far outweighs the small risk of getting endometrial cancer.



Family history. Some studies suggest that endometrial cancer runs in certain families. Women with
inherited mutations in the BRCA1 and BRCA2
genes are at a higher risk of developing breast, ovarian, and other gynecologic cancers. Those with the
hereditary nonpolyposis colorectal cancer gene have
a higher risk of developing endometrial cancer.



Breast, ovarian, or colon cancer. Women who have a
history of these other types of cancer are at an
increased risk of developing endometrial cancer.



Low parity or nulliparity. Endometrial cancer is
more common in women who have born few (low
parity) or no (nulliparity) children. The high levels of
progesterone produced during pregnancy has a protective effect against endometrial cancer. The results
of one study suggest that nulliparity is associated
with a lower survival rate.



Infertility. Risk is increased due to nulliparity or the
use of fertility drugs.



Polycystic ovary syndrome. The increased level of
estrogen associated with this abnormality raises the
risk of cancers of the breast and endometrium.

The most common symptom of endometrial cancer is unusual vaginal spotting, bleeding, or discharge.
In women who are near menopause (perimenopausal),
symptoms of endometrial cancer could include bleeding between periods (intermenstrual bleeding), heavy
bleeding that lasts for more than seven days, or short
menstrual cycles (fewer than 21 days). For women
who have gone through menopause, any vaginal
bleeding or abnormal discharge is suspect. Pain in
the pelvic region and the presence of a lump (mass)
are symptoms that occur late in the disease.

Diagnosis
If endometrial cancer is suspected, a series of tests
will be conducted to confirm the diagnosis. The first
step will involve taking a complete personal and family
medical history. A physical examination, which will
include a thorough pelvic examination, will also be
done.
GALE ENCYCLOPEDIA OF MEDICINE

The doctor may order an endometrial biopsy. This
is generally performed in the doctor’s office and does
not require anesthesia. A thin, flexible tube is inserted
through the cervix and into the uterus. A small piece of
endometrial tissue is removed. The patient may experience some discomfort, which can be minimized by
taking an anti-inflammatory medication (like Advil
or Motrin) an hour before the procedure.
If an adequate amount of tissue was not obtained
by the endometrial biopsy, or if the biopsy tissue looks
abnormal but confirmation is needed, the doctor may
perform a dilatation and curettage (D & C). This procedure is done in the outpatient surgery department of
a hospital and takes about an hour. The patient may
be given general anesthesia. The doctor dilates the
cervix and uses a special instrument to scrape tissue
from inside the uterus.
The tissue that is obtained from the biopsy or the
D & C is sent to a laboratory for examination. If
cancer is found, then the type of cancer will be determined. The treatment and prognosis depends on the
type and stage of the cancer.
Trans-vaginal ultrasound may be used to measure
the thickness of the endometrium. For this painless
procedure, a wand-like ultrasound transducer is
inserted into the vagina to enable visualization and
measurement of the uterus, the thickness of the uterine
lining, and other pelvic organs.
Other possible diagnostic procedures include
sonohysterography and hysteroscopy. For sonohysteroscopy, a small tube is passed through the cervix
and into the uterus. A small amount of a salt water
(saline) solution is injected through the tube to open
the space within the uterus and allow ultrasound
visualization of the endometrium. For hysteroscopy,
a wand-like camera is passed through the cervix to
allow direct visualization of the endometrium. Both
of these procedures cause discomfort, which may be
reduced by taking an anti-inflammatory medication
prior to the procedure.

Treatment
Clinical staging
The International Federation of Gynecology and
Obstetrics (FIGO) has adopted a staging system for
endometrial cancer. The stage of cancer is determined
after surgery. Endometrial cancer is categorized into
four stages (I, II, III, and IV) that are subdivided
(A, B, and possibly C) based on the depth or spread
of cancerous tissue. Seventy percent of all uterine
cancers are stage I, 10–15% are stage II, and the
1323

Endometrial cancer



Endometrial cancer
Cancer located in the uterus. (Illustration by Argosy Inc.)

remainder are stages III and IV. The cancer is also
graded (G1, G2, and G3) based upon microscopic
analysis of the aggressiveness of the cancer cells.
The FIGO stages for endometrial cancer are:


Stage I. Cancer is limited to the uterus.



Stage II. Cancer involves the uterus and cervix.



Stage III. Cancer has spread out of the uterus but is
restricted to the pelvic region.



Stage IV. Cancer has spread to the bladder, bowel, or
other distant locations.

The mainstay of treatment for most stages of
endometrial cancer is surgery. Radiation therapy, hormonal therapy, and chemotherapy are additional treatments (called adjuvant therapy). The necessity of
adjuvant therapy is a controversial topic which should
be discussed with the patient’s treatment team.
Surgery
Most women with endometrial cancer, except
those with stage IV disease, are treated with a hysterectomy. A simple hysterectomy involves the removal
of the uterus. In a bilateral salpingo-oophorectomy
with total hysterectomy, the ovaries, fallopian tubes,
and uterus are removed. This may be necessary
1324

because endometrial cancer often spreads to the ovaries first. The lymph nodes in the pelvic region may also
be biopsied or removed to check for metastasis.
Hysterectomy is traditionally performed through an
incision in the abdomen (laparotomy), however, endoscopic surgery (laparoscopy) with vaginal hysterectomy is also being used. Women with stage I disease
may require no further treatment. However, those
with higher grade disease will receive adjuvant
therapy.
Radiation therapy
The decision to use radiation therapy depends on
the stage of the disease. Radiation therapy may be
used before surgery (preoperatively) and/or after surgery (postoperatively). Radiation given from a
machine that is outside the body is called external
radiation therapy. Sometimes applicators containing
radioactive compounds are placed inside the vagina or
uterus. This is called internal radiation therapy or
brachytherapy and requires hospitalization.
Side effects are common with radiation therapy.
The skin in the treated area may become red and dry.
Fatigue, upset stomach, diarrhea, and nausea are also
common complaints. Radiation therapy in the pelvic
area may cause the vagina to become narrow (vaginal
GALE ENCYCLOPEDIA OF MEDICINE

Chemotherapy
Chemotherapy is usually reserved for women with
stage IV or recurrent disease because this therapy is
not a very effective treatment for endometrial cancer.
The anticancer drugs are given by mouth or intravenously. Side effects include stomach upset, vomiting,
appetite loss, hair loss, mouth or vaginal sores, fatigue,
menstrual cycle changes, and premature menopause.
There is also an increased chance of infections.
Hormonal therapy
Hormonal therapy uses drugs like progesterone to
slow the growth of endometrial cells. These drugs are
usually available as pills. This therapy is usually
reserved for women with advanced or recurrent disease. Side effects include fatigue, fluid retention, and
appetite and weight changes.

Alternative treatment
Although alternative and complementary therapies
are used by many cancer patients, very few controlled
studies on the effectiveness of such therapies exist.
Mind-body techniques, such as prayer, biofeedback,
visualization, meditation, and yoga, have not shown
any effect in reducing cancer, but they can reduce stress
and lessen some of the side effects of cancer treatments.
Clinical studies of hydrazine sulfate found that it had
no effect on cancer and even worsened the health and
well-being of the study subjects. One clinical study of
the drug amygdalin (Laetrile) found that it had no
effect on cancer. Laetrile can be toxic and has caused
deaths. Shark cartilage, although highly touted as an
effective cancer treatment, is an improbable therapy
that has not been the subject of clinical study.
The American Cancer Society has found that the
‘‘metabolic diets’’ pose serious risk to the patient. The
effectiveness of the macrobiotic, Gerson, and Kelley
diets and the Manner metabolic therapy has not been
scientifically proven. The FDA was unable to substantiate the anticancer claims made about the popular Cancell treatment.
There is no evidence for the effectiveness of most
over-the-counter herbal cancer remedies. Some herbals have shown an anticancer effect. As shown in
clinical studies, Polysaccharide krestin, from the
mushroom Coriolus versicolor, has significant effectiveness against cancer. In a small study, the green
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Adjuvant therapy—A treatment done when there is
no evidence of residual cancer in order to aid the
primary treatment. Adjuvant treatments for endometrial cancer are radiation therapy, chemotherapy, and hormone therapy.
Atypical adenomatous hyperplasia—The overgrowth of the endometrium. This precancerous
condition is estimated to progress to cancer in one
third of the cases.
Dilation and curettage (D & C)—A procedure in
which the doctor opens the cervix and uses a special instrument to scrape tissue from the inside of
the uterus.
Endometrial biopsy—A procedure in which a sample of the endometrium is removed and examined
under a microscope.
Endometrium—The mucosal layer lining the inner
cavity of the uterus. The endometrium’s structure
changes with age and with the menstrual cycle.
Estrogen—A female hormone responsible for stimulating the development and maintenance of
female secondary sexual characteristics.
Estrogen replacement therapy (ERT)—A treatment
in which estrogen is used therapeutically during
menopause to alleviate certain symptoms such as
hot flashes. ERT has also been shown to reduce the
risk of osteoporosis and heart disease in women.
Progesterone—A female hormone that acts on the
inner lining of the uterus and prepares it for implantation of the fertilized egg.
Progestins—A female hormone, like progesterone,
that acts on the inner lining of the uterus.

alga Chlorella pyrenoidosa has been shown to have
anticancer activity. In a few small studies, evening
primrose oil has shown some benefit in the treatment
of cancer.

Prognosis
Because it is possible to detect endometrial cancer
early, the chances of curing it are excellent. The five
year survival rates for endometrial cancer by stage are:
90%, stage I; 60%, stage II; 40%, stage III; and 5%,
stage IV. Endometrial cancer most often spreads to
the lungs, liver, bones, brain, vagina, and certain
lymph nodes.
1325

Endometrial cancer

stenosis), making intercourse painful. Premature
menopause and some problems with urination may
also occur.

Endometriosis

Prevention
Women (especially postmenopausal women)
should report any abnormal vaginal bleeding or discharge to the doctor. Controlling obesity, blood pressure, and diabetes can help to reduce the risk of this
disease. Women on estrogen replacement therapy
have a substantially reduced risk of endometrial cancer if progestins are taken simultaneously. Long term
use of birth control pills has been shown to reduce the
risk of this cancer. Women who have irregular periods
may be prescribed birth control pills to help prevent
endometrial cancer. Women who are taking tamoxifen
and those who carry the hereditary nonpolyposis colorectal cancer gene should be screened regularly,
receiving annual pelvic examinations.

Gynecologic Cancer Foundation. 401 North Michigan Ave.,
Chicago, IL 60611. (800) 444-4441. <http://
www.wcn.org>.
National Cancer Institute, National Institutes of Health.
9000 Rockville Pike, Bethesda, MD 20892. (800)
422-6237. <http://cancernet.nci.nih.gov/>.
OTHER

‘‘Cancer of the Uterus.’’ Cancernet. December 2000. [cited
March 13, 2001]. <http://cancernet.nci.nih.gov/
wyntk_pubs/uterus.htm>.

Lata Cherath, PhD
Belinda Rowland, PhD

Resources
BOOKS

Bruss, Katherine, Christina Salter, and Esmeralda Galan,
editors. American Cancer Society’s Guide to
Complementary and Alternative CancerMethods.
Atlanta: American Cancer Society, 2000.
Burke, Thomas, Patricia Eifel, and Muggia Franco. ‘‘Cancers
of the Uterine Body.’’ In Cancer: Principles & Practice of
Oncology, edited by Vincent DeVita, Samuel Hellman,
and Steven Rosenberg. Philadelphia: Lippincott
Williams & Wilkins, 2001, pp. 1573– 86.
Long, Harry. ‘‘Carcinoma of the Endometrium.’’ In Current
Therapy in Cancer, edited by John Foley, Julie Vose,
and James Armitage. Philadelphia: W. B. Saunders
Company, 1999, pp. 162–66.
Primack, Aron. ‘‘Complementary/Alternative Therapies
inthe Prevention and Treatment of Cancer.’’ In
Complementary/Alternative Medicine:An EvidenceBased Approach, edited by John Spencer and Joseph
Jacobs. St. Louis: Mosby, 1999, pp. 123–69.
PERIODICALS

Bristow, Robert. ‘‘Endometrial Cancer.’’ Current Opinion in
Oncology 11 (Septerem 1999): 388–393.
Canavan, Timothy, and Nipa Doshi. ‘‘Endometrial Cancer.’’
American Family Physician 59 (June 1999): 3069–3077.
Elit, Laurie. ‘‘Endometrial Cancer: Prevention, Detection,
Management, and Follow up.’’ Canadian Family
Physician 46 (April 2000): 887–892.
Hogberg, Thomas, Margareta Fredstorp, and Anuja
Jhingran. ‘‘Indications for Adjuvant Radiotherapy in
Endometrial Carcinoma.’’ Hematology/Oncology
Clinics of North America: Current Therapeutic Issues in
Gynecologic Cancer 13 (February 1999): 189–209.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta, GA
30329. (800) 227-2345. <http://www.cancer.org/>.
Cancer Research Institute, National Headquarters. 681
Fifth Ave., New York, NY 10022. (800) 992-2623.
<http://www.cancerresearch.org>.
1326

Endometriosis
Definition
Endometriosis is a condition in which bits of the
tissue similar to the lining of the uterus (endometrium)
grow in other parts of the body. Like the uterine lining,
this tissue builds up and sheds in response to monthly
hormonal cycles. However, there is no natural outlet
for the blood discarded from these implants. Instead,
it falls onto surrounding organs, causing swelling and
inflammation. This repeated irritation leads to the
development of scar tissue and adhesions in the area
of the endometrial implants.

Description
Endometriosis is estimated to affect 7% of women
of childbearing age in the United States. It most commonly strikes between the ages of 25 and 40.
Endometriosis can also appear in the teen years, but
never before the start of menstruation. It is seldom
seen in postmenopausal women.
Endometriosis was once called the ‘‘career
woman’s disease’’ because it was thought to be a product of delayed childbearing. The statistics defy such a
narrow generalization; however, pregnancy may slow
the progress of the condition. A more important predictor of a woman’s risk is if her female relatives have
endometriosis. Another influencing factor is the
length of a woman’s menstrual cycle. Women whose
periods last longer than a week with an interval of less
than 27 days between them seem to be more prone to
the condition.
Endometrial implants are most often found on the
pelvic organs—the ovaries, uterus, fallopian tubes,
and in the cavity behind the uterus. Occasionally,
GALE ENCYCLOPEDIA OF MEDICINE

experience reversed menstrual flow while relatively
few develop endometriosis.


While many women with endometriosis suffer
debilitating symptoms, others have the disease without knowing it. Paradoxically, there does not seem to
be any relation between the severity of the symptoms
and the extent of the disease. The most common symptoms are:


Menstrual pain. Pain in the lower abdomen that
begins a day or two before the menstrual period
starts and continues through to the end is typical of
endometriosis. Some women also report lower back
aches and pain during urination and bowel movement, especially during their periods.



Painful sexual intercourse. Pressure on the vagina
and cervix causes severe pain for some women.



Abnormal bleeding. Heavy menstrual periods, irregular bleeding, and spotting are common features of
endometriosis.



Infertility. There is a strong association between
endometriosis and infertility, although the reasons
for this have not been fully explained. It is thought
that the build up of scar tissue and adhesions blocks
the fallopian tubes and prevents the ovaries from
releasing eggs. Endometriosis may also affect fertility
by causing hormonal irregularities and a higher rate
of early miscarriage.

Causes and symptoms
Although the exact cause of endometriosis is
unknown, a number of theories have been put
forward. Some of the more popular ones are:


Implantation theory. Originally proposed in the
1920s, this theory states that a reversal in the direction
of menstrual flow sends discarded endometrial cells
into the body cavity where they attach to internal
organs and seed endometrial implants. There is considerable evidence to support this explanation.
Reversed menstrual flow occurs in 70–90% of
women and is thought to be more common in women
with endometriosis. However, many women with
reversed menstrual flow do not develop endometriosis.



Vascular-lymphatic theory. This theory suggests that
the lymph system or blood vessels (vascular system)
is the vehicle for the distribution of endometrial cells
out of the uterus.



Coelomic metaplasia theory. According to this
hypothesis, remnants of tissue left over from prenatal
development of the woman’s reproductive tract transforms into endometrial cells throughout the body.



Induction theory. This explanation postulates that
an unidentified substance found in the body forces
cells from the lining of the body cavity to change into
endometrial cells.

In addition to these theories, the following factors
are thought to influence the development of
endometriosis:


Heredity. A woman’s chance of developing endometriosis is seven times greater if her mother or sisters
have the disease.



Immune system function. Women with endometriosis may have lower functioning immune systems that
have trouble eliminating stray endometrial cells. This
would explain why a high percentage of women

GALE ENCYCLOPEDIA OF MEDICINE

Dioxin exposure. Some research suggests a link
between the exposure to dioxin (TCCD), a toxic
chemical found in weed killers, and the development
of endometriosis.

Diagnosis
If a doctor suspects endometriosis, the first step
will be to perform a pelvic exam to try to feel if
implants are present. Very often there is no strong
evidence of endometriosis from a physical exam. The
only way to make a definitive diagnosis is through
minor surgery called a laparoscopy. A laparoscope, a
slender scope with a light on the end, is inserted into
the woman’s abdomen through a small incision near
her belly button. This allows the doctor to examine the
internal organs for endometriotic growths. Often, a
sample of tissue is taken for later examination in the
laboratory. Endometriosis is sometimes discovered
when a woman has abdominal surgery for another
reason such as tubal ligation or hysterectomy.
Various imaging techniques such as ultrasound,
computed tomography scan (CT scan), or magnetic
resonance imaging (MRI) can offer additional
1327

Endometriosis

this tissue grows in such distant parts of the body as
the lungs, arms, and kidneys. Newly formed implants
appear as small bumps on the surfaces of the organs
and supporting ligaments and are sometimes said to
look like ‘‘powder burns.’’ Ovarian cysts may form
around endometrial tissue (endometriomas) and may
range from pea to grapefruit size. Endometriosis is a
progressive condition that usually advances slowly,
over the course of many years. Doctors rank cases
from minimal to severe based on factors such as the
number and size of the endometrial implants, their
appearance and location, and the extent of the scar
tissue and adhesions in the vicinity of the growths.

Endometriosis

hoping to become pregnant would take these medications for a period of time, then try to conceive within
several months of discontinuing treatment.

An endoscopic view of endometriosis on pelvic wall. (Custom
Medical Stock Photo. Reproduced by permission.)

information but aren’t useful in making the initial diagnosis. A blood test may also be ordered because women
with endometriosis have higher levels of the blood protein CA125. Testing for this substance before and after
treatment can predict a recurrence of the disease, but
the test is not reliable as a diagnostic tool.

Treatment
How endometriosis is treated depends on the
woman’s symptoms, her age, the extent of the disease,
and her personal preferences. The condition cannot be
fully eradicated without surgery. Conservative treatment focuses on managing the pain, preserving fertility, and delaying the progress of the condition.
Pain relief
Over-the-counter pain relievers such as aspirin
and acetaminophen (Tylenol) are useful for mild
cramping and menstrual pain. Prescription-strength
and over-the-counter nonsteroidal anti-inflammatory
drugs (NSAIDs), such as ibuprofen (Motrin, Advil)
and naproxen (Naprosyn), are also effective. If pain is
severe, a doctor may prescribe narcotic medications,
although these can be addicting and are rarely used.
Hormonal treatments
Hormonal therapies effectively tame endometriosis but also act as contraceptives. A woman who is
1328



Oral contraceptives. Continuously taking estrogenprogestin pills tricks the body into thinking it is
pregnant. This state of pseudopregnancy means
reduced pelvic pain and a temporary withering of
endometrial implants.



Danazol (Danocrine) and gestrinone are synthetic
male hormones that lower estrogen levels, prevent
menstruation, and shrink endometrial tissues. On the
downside, they lead to weight gain and menopauselike symptoms, and cause some women to develop
masculine characteristics.



Progestins. Medroxyprogesterone (Depo-Provera)
and related drugs may also be used in treating endometriosis. They have been proven effective in minimizing pain and halting the progress of the
condition, but are rarely used because of the high
rate of side effects.



Gonadotropin-releasing hormone (GnHR) agonists.
These estrogen-inhibiting drugs successfully limit
pain and prevent the growth of endometrial
implants. They can cause menopause symptoms,
however, and doses have to be regulated to prevent
bone loss associated with low estrogen levels.
Surgery

Removing the uterus, ovaries, and fallopian tubes
is the only permanent method of eliminating endometriosis. This is an extreme measure that deprives a
woman of her ability to bear children and forces her
body into menopause. Endometrial implants and
ovarian cysts can be removed with laser surgery performed through a laparoscope. For women with minimal endometriosis, this technique is usually successful
in reducing pain and slowing the condition’s progress.
It may also help infertile women increase their chances
of becoming pregnant.

Alternative treatment
Although severe endometriosis should not be selftreated, many women find they can help their condition through alternative therapies. Taking vitamin B
complex combined with vitamins C, E, and the minerals calcium, magnesium, and selenium can help the
depression and lack of energy that may accompany
endometriosis. B vitamins also counteract the side
effects of hormonal drugs. Other women have found
relief when they turned to a macrobiotic diet. Less
extreme diets that cut out sugar, salt, and processed
GALE ENCYCLOPEDIA OF MEDICINE

Adhesions—Web-like scar tissue that may develop
as a result of endometriosis and bind organs to one
another.
Dioxin—A toxic chemical found in weed killers
that has been linked to the development of
endometriosis.
Endometrial implants—Growths of endometrial
tissue that attach to organs, primarily in the pelvic
cavity.
Endometrium—The tissue lining the uterus that
grows and sheds each month during a woman’s
menstrual cycle.
Estrogen—A female hormone that promotes the
growth of endometrial tissue.
Hormonal therapy—Use of hormone medications
to inhibit menstruation and relieve the symptoms of
endometriosis.
Laparoscopy—A diagnostic procedure for endometriosis performed by inserting a slender, wandlike instrument through a small incision in the
woman’s abdomen.
Menopause—The end of a woman’s menstrual periods when the body stops making estrogen.
Retrograde menstruation—Menstrual flow that travels into the body cavity rather than being expelled
through the uterus.

foods are sometimes helpful, as well. Mind-body
therapies such as relaxation and visualization help
women cope with pain. Other avenues to combat
pain include acupuncture and biofeedback techniques.
Still other women report positive results after being
treated by chiropractors or homeopathic doctors.

Prognosis
Most women who have endometriosis have minimal symptoms and do well. Overall, endometriosis
symptoms come back in an average of 40% of
women over the five years following treatment. With
hormonal therapy, pain returned after five years in
37% of patients with minimal symptoms and 74% of
those with severe cases. The highest success rate from
conservative treatment followed complete removal of
implants using laser surgery. Eighty percent of these
women were still pain-free five years later. In cases
that don’t respond to these treatments, a woman and
GALE ENCYCLOPEDIA OF MEDICINE

her doctor may consider surgery to remove her reproductive organs.

Prevention
There is no proven way to prevent endometriosis.
One study, however, indicated that girls who begin
participating in aerobic exercise at a young age are
less likely to develop the condition.
Resources
ORGANIZATIONS

Endometriosis Association International Headquarters.
8585 North 76th Place, Milwaukee, WI 53223. (800)
992-3636. <http://EndometriosisAssn.org>.

Stephanie Slon

Endometritis see Pelvic inflammatory
disease

Endorectal ultrasound
Definition
Endorectal ultrasound (ERUS) is a procedure
where a probe is inserted into the rectum and high
frequency sound waves (ultrasound waves) are generated. The pattern of echoes as they bounce off tissues is
converted into a picture (sonogram) on a television
screen.

Purpose
ERUS is used as a diagnostic procedure in rectal
cancer to determine stage of the tumor and as a postradiation, presurgical examination to assess extent of
tumor shrinkage. ERUS can also be used in cases of
anal fistula (an abnormal passage) and problems with
the anal sphincter muscles (muscles that control the
opening and closing of the anus).

Precautions
Normal precautions should be taken with any
diagnostic procedure. Since the population in which
this procedure is normally done is elderly, the imaging
staff should be extra cautious about stressing the
patient. The procedure is invasive and may be embarrassing to some. Other patients may be anxious about
their medical condition since endorectal ultrasounds
are not routine. This places an added burden on
1329

Endorectal ultrasound

KEY TERMS

Endoscopic retrograde cholangiopancreatography

Normal results

KEY TERMS
Anal sphincter muscles—Muscles that control the
opening and closing of the anus.
Fistula—An abnormal passage.
Sonogram—The picture formed by the pattern of
echoes from an ultra sound.
Ultrasound waves—High frequency sound waves.

Normal results after an endorectal ultrasound are
normal, healthy tissues.

Abnormal results
Abnormal results range from any number of congenital deformities in the lining of the rectum to serious rectal cancers.
Resources
BOOKS

already stressed hearts and nervous systems.
Physicians, nurses, and technicians may need to be
prepared for stress reactions that could include the
heart, asthma, or anxious behaviors.

Description

Johnston, Lorraine. Colon and Rectal Cancer: A
Comprehensive Guide for Patients and Families.
Sebastopol, CA: O’Reilly, 2000.
Levin, Bernard. Colorectal Cancer: A Thorough and
Compassionate Resource for Patients and Their
Families. New York: Villard, 1999.
PERIODICALS

ERUS has been used as a means to determine the
depth of rectal cancers and to assess whether the
tumor has affected surrounding tissues. This pre-treatment procedure has proven to be an accurate tool for
tailoring surgery for patients.

Gavioli, M. A. Bagni, I. Piccagli, S. Fundaro, and
G. Natalini. ‘‘Usefulness of Endorectal Ultrasound
after Preoperative Radiotherapy in Rectal Cancer:
Comparison between Sonographic and
Histopathologic Changes.’’ Dis ColonRectum (August
2000): 1075-83.

Problems with interpretation of the sonograms
after radiation and before surgery have resulted in
tumors being identified that were merely the formation of fibrous tissues that remained after the tumors
had been eliminated by the radiation. Yet, some of the
fibrous areas actually hid residual tumors. Rectal
anatomy itself can affect the accuracy of ultrasound
reading. This makes ERUS problematic in determining the amount of tumor reduction a patient has after
radiation therapy.

OTHER

American Society of Colon and Rectal Surgeons.‘‘Practice
Parameters for the Treatment of Rectal Carcinoma.’’
May 9, 2001. <http://www.asco.org/prof/me/html/
abstracts/gasc/m_969.htm>.
National Cancer Institute. ‘‘NCI/PDQ Patient
Statement:Rectal Cancer Updated 11/2000.’’ OncoLink.
May 9, 2001. <http://www.oncolink.upenn.edu/
pdq_html/2/engl/200076.html>.

Janie F. Franz

Preparation
The patient must evacuate the bowels completely
before the procedure is done. This usually is assisted
though the use of several enemas. The patient may be
told to adhere to a liquid diet the day prior to doing
this procedure. The probe is inserted, usually with
little discomfort for the patient since it will only be
examining the first few inches of the colon.

Aftercare
Since ERUS is a minor invasive procedure, there
is no aftercare.

Risks
There are no risks to having an ultrasound.
1330

Endoscopic retrograde
cholangiopancreatography
Definition
Endoscopic retrograde cholangiopancreatography (ERCP) is a technique in which a hollow tube
called an endoscope is passed through the mouth and
stomach to the duodenum (the first part of the small
intestine). This procedure was developed to examine
abnormalities of the bile ducts, pancreas, and gallbladder. It was developed during the late 1960s and is used
today to diagnose and treat blockages of the bile and
pancreatic ducts.
GALE ENCYCLOPEDIA OF MEDICINE



endoscopic refers to the use of an endoscope



retrograde refers to the injection of dye up into the
bile ducts in a direction opposing, or against, the
normal flow of bile down the ducts



cholangiopancreatography means visualization of
the bile ducts (cholangio) and pancreas (pancreato)

Purpose
Until the 1970s, methods to visualize the bile ducts
produced images that were of relatively poor quality
and often misleading; in addition, the pancreatic duct
could not be examined at all. Patients with symptoms
related to the bile ducts or pancreatic ducts frequently
needed surgery to diagnose and treat their conditions.
Using ERCP, physicians can obtain high-quality x
rays of these structures and identify areas of narrowing
(strictures), cancers, and gallstones. This procedure can
help determine whether bile or pancreatic ducts are
blocked; it also identifies where they are blocked
along with the cause of the blockage. ERCP may then
be used to relieve the blockage. For patients requiring
surgery or additional procedures for treatment, ERCP
outlines the anatomical changes for the surgeon.

Precautions
The most important precaution is that the examination should be performed by an experienced physician. The procedure is much more technically difficult
than many other gastrointestinal endoscopic studies.
Patients should seek physicians with experience performing ERCP. Patients should inform the physician
about any allergies (including allergies to contrast
dyes, iodine, or shellfish), medication use, and medical
problems. Occasionally, patients may need to be
admitted to the hospital after the procedure.

Description
After sedation, a specially adapted endoscope is
passed through the mouth, through the stomach, then
into the duodenum. The opening to ducts that empty
from the liver and pancreas is identified, and a plastic
tube or catheter is placed into the orifice (opening).
Contrast dye is then injected into the ducts, and with
the assistance of a radiologist, pictures are taken.

Preparation
The upper intestinal tract must be empty for the
procedure, so patients should not eat or drink for at
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Endoscope, endoscopy—An endoscope used in the
field of gastroenterology is a hollow, thin, flexible
tube that uses a lens or miniature camera to view
various areas of the gastrointestinal tract. When the
procedure is performed to examine the bile ducts or
pancreas, the organs are not viewed directly, but
rather indirectly through the injection of contrast.
The performance of an exam using an endoscope is
referred to as endoscopy. Diagnosis through biopsies or other means and therapeutic procedures can
also be done using these instruments.
Visualization—The process of making an internal
organ visible. A radiopaque substance is introduced into the body, then an x-ray picture of the
desired area is taken.

least six to 12 hours before the exam. Patients should
ask the physician about taking their medications
before the procedure.

Aftercare
Someone should be available to take the person
home after the procedure and stay with them for a
while; patients will not be able to drive themselves
because they undergo sedation during this test. Pain
or any other unusual symptoms should be reported to
the physician.

Risks
ERCP-related complications can be broken down
into those related to medications used during the procedure, the diagnostic part of the procedure, and those
related to endoscopic therapy. The overall complication rate is 5–10%; most of those occur when diagnostic ERCP is combined with a therapeutic procedure.
During the exam, the endoscopist can cut or stretch
structures (such as the muscle leading to the bile duct)
to treat the cause of the patient’s symptoms. Although
the use of sedatives carries a risk of decreasing cardiac
and respiratory function, it is very difficult to perform
these procedures without these drugs.
The major complications related to diagnostic
ERCP are pancreatitis (inflammation of the pancreas)
and cholangitis (inflammation of the bile ducts).
Bacteremia (the passage of bacteria into the blood
stream) and perforation (hole in the intestinal tract)
are additional risks.
1331

Endoscopic retrograde cholangiopancreatography

The term has three parts to its definition:

Endoscopic sphincterotomy

Normal results
Because certain standards have been set for the
normal diameter or width of the pancreatic duct and
bile ducts, measurements using x rays are taken to
determine if the ducts are too large (dilated) or too
narrow (strictured). The ducts and gallbladder should
be free of stones or tumors.

Abnormal results
When areas in the pancreatic or bile ducts (including those in the liver) are too wide or too narrow
compared with the standard, the test is considered
abnormal. Once these findings are demonstrated
using ERCP, symptoms are usually present; they generally do not change without treatment. Stones, identified as opaque or solid structures within the ducts,
are also considered abnormal. Masses or tumors may
also be seen, but sometimes the diagnosis is made not
by direct visualization of the tumor, but by indirect
signs, such as a single narrowing of one of the ducts.
Overall, ERCP has an excellent record in diagnosing
these abnormalities.
Resources
OTHER

Endoscopic Retrograde Cholangiopancreatography. [cited
June 21, 2004]. <http://www.asge.org>.
Measuring Procedural Skills. [cited June 21, 2004]. <http://
www.acponline.org/journals/annals/15dec96/
procskil.htm>.
Treatment of Acute Biliary Pancreatitis. [cited June 21, 2004].
<http://content.nejm.org>.

David Kaminstein, MD

Endoscopic sclerotherapy see Sclerotherapy
for esophageal varices

Endoscopic sphincterotomy
Definition
Endoscopic sphincterotomy or endoscopic retrograde sphincterotomy (ERS) is a relatively new endoscopic technique developed to examine and treat
abnormalities of the bile ducts, pancreas and gallbladder. The procedure was developed as an extension to
the diagnostic examination, ERCP (endoscopic retrograde cholangiopancreatography); with the addition
of ‘‘sphincterotomy,’’ abnormalities found during the
1332

study could be treated at the same time without the
need for invasive surgery.
The term ERS has three parts to its definition;


endoscopic refers to the use of an endoscope



retrograde refers to the insertion of the endoscope up
into the ducts in a direction opposite to or against the
normal flow of bile down the ducts



sphincterotomy, which means cutting of the sphincter or muscle that lies at the juncture of the intestine
with both the bile and pancreatic ducts.

Purpose
Until the 1970s, patients with symptoms related to
disease of the bile ducts or pancreas frequently needed
surgery to diagnose the cause and treat any abnormalities. ERCP allowed physicians for the first time to
obtain high quality x rays of the common bile and
pancreatic ducts, and detect areas of narrowing (strictures), stones, and tumors. ERCP was not initially
designed for treatment. ERS was developed shortly
after and enabled physicians to treat the abnormalities
identified by the injection of dye and x rays.
The revolutionary technique made possible the
endoscopic removal of stones and stretching of areas
of narrowing (strictures). It has since been expanded
to include drainage of bile from blocked ducts and
treatment of various abnormalities of the pancreas.

Precautions
The most important precaution related to both
ERCP and ERS is to have the procedure performed
by an experienced physician. ERS is technically more
difficult than many other gastrointestinal endoscopic
studies, including ERCP. Patients should inquire as to
the physician’s experience with the procedure. The
physician should also be informed of any allergies,
medication use, and medical problems.

Description
ERS is generally performed only after ERCP has
been successfully accomplished and detail of the anatomy and abnormalities is known. During ERS, a number of various instruments are inserted through the
endoscope in order to ‘‘cut’’ or stretch the sphincter.
Once this is done, additional instruments are passed
that enable the removal of stones and the stretching of
narrowed regions of the ducts. Drains (stents) can also
be used to prevent a narrowed area from rapidly returning to its previously narrowed state.
GALE ENCYCLOPEDIA OF MEDICINE

Endoscope, Endoscopy—An endoscope as used in
the field of gastroenterology is a thin flexible tube
which uses a lens or miniature camera to view
various areas of the gastrointestinal tract. When
the procedure is performed to examine certain
organs such as the bile ducts or pancreas, the
organs are not viewed directly, but rather indirectly
through the injection of x-ray dye. The performance of an exam using an endoscope is referred
by the general term endoscopy. Diagnosis through
biopsies or other means and therapeutic procedures can be done with these instruments.
NSAIDS—This abbreviation stands for non-steroidal anti-inflammatory drugs, which are medications such as Ibufprofen that are used to control
pain and inflammation. Most may be purchased
over the counter. One of their major side effects is
that they decrease the effect of the normal blood
clotting factors in blood. In patients undergoing
surgical or endoscopic procedures, this can lead
to an increased risk of bleeding.

Preparation
The upper intestinal tract must be empty for the
procedure, so patients must not eat or drink for at least
six to 12 hours before the exam. Patients need to
inquire about taking their medications before the procedure. Some patients may require antibiotics before
and/or after the procedure. When possible, aspirin or
NSAIDS should not be taken within several days
before the procedure, because they interfere with
blood clotting.

bile duct) to treat the cause of the patient’s symptoms.
Cutting or stretching of these structures can sometimes cause a hole or perforation. The use of sedatives
also carries a risk of decreasing cardiac and respiratory function, however, it is very difficult to perform
these procedures without these drugs.
Other major complications related to ERCP or
ERS are pancreatitis (inflammation of the pancreas)
and cholangitis (inflammation of the bile ducts).
Bacteremia (the passage of bacteria into the blood
stream) and bleeding are also risks.

Normal results
Certain standards have been set for the diameter
or width of the pancreatic and bile ducts.
Measurements by x ray are used to determine if the
ducts are too large (dilated) or too narrow (strictured).
Lastly, the ducts and gallbladder should be free of any
solid particles, such as stones, and free of areas of
narrowing.
Resources
OTHER

‘‘Endoscopic Retrograde
Cholangiopancreatography.’’American Society for
Gastrointestinal Endoscopy. <http://www.asge.org>.
‘‘Treatment of Acute Biliary Pancreatitis.’’ New England
Journal of Medicine Online.<http://
content.nejm.org>.

David Kaminstein, MD

Enemas
Definition

Aftercare
When ERS is performed, physicians will usually
want to observe the patient closely for several hours to
ensure that there are no signs of complications. Pain or
any other unusual symptoms should be reported.
Admission to the hospital may be advised.

An enema is the insertion of a solution into the
rectum and lower intestine.

Purpose
Enemas may be given for the following purposes:


to remove feces when an individual is constipated or
impacted,



to remove feces and cleanse the rectum in preparation for an examination,



to remove feces prior to a surgical procedure to prevent contamination of the surgical area,



to administer drugs or anesthetic agents.

Risks
ERS complications are related either to the drugs
used during the procedure, or the results of dye injection or cutting of tissue. The overall complication rate
is 5–10%. During the exam, the endoscopist can cut or
stretch structures (such as the muscle leading to the
GALE ENCYCLOPEDIA OF MEDICINE

1333

Enemas

KEY TERMS

Enemas

Precautions
The rectal tube used for infusion of the enema
solution should be smooth and flexible to decrease
the possibility of damage to the mucous membrane
that lines the rectum. Tap water is commonly used for
adults but should not be used for infants because of the
danger of electrolyte (substance that conducts electric
current within the body and is essential for sustaining
life) imbalance. The colon absorbs water, and repeated
tap water enemas can cause cardiovascular overload
and electrolyte imbalance. Similarly, repeated saline
enemas can cause increased absorption of fluid and
electrolytes into the bloodstream, resulting in overload. Individuals receiving frequent enemas should
be observed for overload symptoms that include dizziness, sweating, or vomiting.
Soap suds and saline used for cleansing enemas
can cause irritation of the lining of the bowel, with
repeated use or a solution that is too strong. Only
white soap should be used; the bar should not have
been previously used, to prevent infusing undesirable
organisms into the individual receiving the enema.
Common household detergents are considered too
strong for the rectum and bowel. The commercially
prepared castile soap is preferred, and should be used
in concentration no greater than 5 cc soap to 1,000 cc
of water.

Description
Cleansing enemas act by stimulation of bowel
activity through irritation of the lower bowel, and by
distention with the volume of fluid instilled. When the
enema is administered, the individual is usually lying
on the left side, which places the sigmoid colon (lower
portion of bowel) below the rectum and facilitates
infusion of fluid. The length of time it takes to administer an enema depends on the amount of fluid to be
infused. The amount of fluid administered will vary
depending on the age and size of the person receiving
the enema, however general guidelines would be:


Infant: 250 cc or less



Toddler and preschooler: 500 cc or less



School-aged child: 500–1,000 cc



Adult: 750–1,000 cc

Some may differentiate between high and low
enemas. A high enema, given to cleanse as much of
the large bowel as possible, is usually administered at
higher pressure and with larger volume (1,000 cc),
and the individual changes position several times in
order for the fluid to flow up into the bowel. A low
1334

Colon

Rectum

Enemas may be given for the following purposes: to remove
feces when an individual is constipated, or to remove feces
and cleanse the rectum in preparation for an examination, or
prior to surgery to prevent contamination. There are two
types of enemas: the high enema, given to cleanse the large
bowel, and the low enema, to cleanse only the lower bowel.
(Illustration by Electronic Illustrators Group.)

enema, intended to cleanse only the lower bowel, is
administered at lower pressure, using about 500 cc of
fluid.
Oil retention enemas serve to lubricate the rectum
and lower bowel, and soften the stool. For adults,
about 150–200 cc of oil is instilled, while in small
children, 75–150 cc of oil is considered adequate.
Salad oil or liquid petrolatum are commonly used at
a temperature of 918F (32.88C). There are also commercially prepared oil retention enemas. The oil is
usually retained for one to three hours before it is
expelled.
The rectal tube used for infusion of the solution,
usually made of rubber or plastic, has two or more
openings at the end through which the solution can
flow into the bowel. The distance to which the tube
must be inserted is dependent upon the age and size of
the patient. For adult, insertion is usually 3–4 in
(7.5–10 cm); for children, approximately 2–3 in
(5–7.5 cm); and for infants, only 1–1.5 in (2.5–3.75 cm).
The rectal tube is lubricated before insertion with a
water soluble lubricant to ease insertion and decrease
irritation to the rectal tissues.
The higher the container of solution is placed, the
greater the force in which the fluid flows into the
patient. Routinely, the container should be no higher
than 12 in (30 cm) above the level of the bed; for a
high cleansing enema, the container may be 12–18 in
(30–45 cm) above the bed level, because the fluid is to
be instilled higher into the bowel.
GALE ENCYCLOPEDIA OF MEDICINE

Electrolyte—A substance that conducts electric
current within the body and is essential for sustaining life.
Intestine—Also called the bowels and divided into
large and small intestine, they extend from the
stomach to the anus, where waste products exit
the body. The small intestine is about 20 ft (6.1m)
long and the large intestine, about 5 ft (1.5m) long.
Rectum—The portion of bowel just before the anus.
The prefix recto is used with a variety of words in
relation to conditions that affect the rectum.

Preparation
The solution used in the procedure is measured,
mixed, and warmed before administration of the enema.

Aftercare
If necessary, a specimen will be collected for diagnostic evaluation. If the enema was given to alleviate
constipation, the better approach to combatting constipation in the future is with a high fiber diet (five to
six servings of whole grain foods) and adequate fluid
intake (seven to eight glasses of water per day).
Regular exercise and going to the bathroom when
necessary will also help. If constipation is a chronic
problem, medical help should be consulted to determine if there is underlying disorder.

Risks
Habitual use of enemas as a means to combat
constipation can make the problem even more severe
when their use is discontinued. Enemas should be used
only as a last resort for treatment of constipation and
with a doctor’s recommendation. Enemas should not
be administered to individuals who have recently had
colon or rectal surgery, a heart attack, or who suffer
from an unknown abdominal condition or an irregular heartbeat.
Resources
OTHER

Eller, D. ‘‘Spring Cleaning from the Inside Out.’’ Remedy
May/June 1997. [cited May 28, 1998]. <http://
thriveonline.oxygen.com>.

Kathleen D. Wright, RN
GALE ENCYCLOPEDIA OF MEDICINE

Enlarged prostate
Definition
A non-cancerous condition that affects many men
past 50 years of age, enlarged prostate makes urinating
more difficult by narrowing the urethra, a tube running from the bladder through the prostate gland. It
can be effectively treated by surgery and, today, by
certain drugs.

Description
The common term for enlarged prostate is BPH,
which stands for benign (non-cancerous) prostatic hyperplasia or hypertrophy. Hyperplasia means that the prostate cells are dividing too rapidly, increasing the total
number of cells, and, therefore, the size of the organ itself.
Hypertrophy simply means ‘‘enlargement.’’ BPH is part
of the aging process. The actual changes in the prostate
may start as early as the 30s but take place very gradually,
so that significant enlargement and symptoms usually do
not appear until after age 50. Past this age the chances of
the prostate enlarging and causing urinary symptoms
become progressively greater. More than 40% of men
in their 70s have an enlarged prostate. Symptoms generally appear between ages 55–75. About 10% of all men
eventually will require treatment for BPH.
BPH has been viewed as a rare condition in
African, Chinese, and other Asian peoples for reasons
that are not clear.

Causes and symptoms
The cause of BPH is a mystery, but age-related
changes in the levels of hormones circulating in the
blood may be a factor. Whatever the cause, an enlarging
prostate gradually narrows the urethra and obstructs the
flow of urine. Even though the muscle in the bladder wall
becomes stronger in an attempt to push urine through the
smaller urethra, in time, the bladder fails to empty completely at each urination. The urine that collects in the
bladder can become infected and lead to stone formation.
The kidneys themselves may be damaged by infection or
by urine constantly ‘‘backing up.’’
When the enlarging prostate gland narrows the
urethra, a man will have increasing trouble starting
the urine stream. Because some urine remains behind
in the bladder, he will have to urinate more often,
perhaps two or three times at night (nocturia). The
need to urinate can become very urgent and, in time,
urine may dribble out to stain a man’s clothing. Other
symptoms of BPH are a weak and sometimes a split
1335

Enlarged prostate

KEY TERMS

Enlarged prostate

Urine retention in bladder

Ureter
Enlarged
prostate
gland

Prostate
gland

Constricted
urethra

Normal sized prostate gland

Enlarged prostate gland

An enlarged prostate is a non-cancerous condition in which the narrowing of the urethra makes the elimination of urine more
difficult. It most often occurs in men over age 50. (Illustration by Electronic Illustrators Group.)

stream and general aching or pain in the perineum (the
area between the scrotum and anus). Some men may
have considerable enlargement of the prostate before
even mild symptoms develop.
If a man must strain hard to force out the urine,
small veins in the bladder wall and urethra may rupture,
causing blood to appear in the urine. If the urinary
stream becomes totally blocked, the urine collecting in
the bladder may cause severe discomfort, a condition
called acute urinary retention. Urine that stagnates in
the bladder can easily become infected. A burning feeling during urination and fever are clues that infection
may have developed. Finally, if urine backs up long
enough it may increase pressure in the kidneys, though
this rarely causes permanent kidney damage.

Diagnosis
When a man’s symptoms point to BPH, the first
thing the physician will want to do is a digital rectal
examination, inserting a finger into the anus to feel
whether—and how much—the prostate is enlarged. A
smooth prostate surface suggests BPH, whereas a distinct lump in the gland might mean prostate cancer. The
next step is a blood test for a substance called prostatespecific antigen or PSA. Between 30–50% of men with
1336

BPH have an elevated PSA level. This does not mean
cancer by any means, but other measures are needed to
make sure that the prostate enlargement is in fact
benign. An ultrasound exam of the prostate, which is
entirely safe and delivers no radiation, can show whether
it is enlarged and may show that cancer is present.
If digital or ultrasound examination of the prostate raises the suspicion of cancer, most urologists will
recommend that a prostatic tissue biopsy be performed. This is usually done using a lance-like instrument that is inserted into the rectum. It pierces the
rectal wall and, guided by the physcian’s finger,
obtains six to eight pieces of prostatic tissue that are
sent to the laboratory for microscopic examination. If
cancer is present, the prognosis and treatment are
changed accordingly.
A catheter placed through the urethra and into the
bladder can show how much urine remains in the
bladder after the patient urinates—a measure of how
severe the obstruction is. Another and very simple test
for obstruction is to have the man urinate into a uroflowmeter, which measures the rate of urine flow. A
very certain—though invasive—way of confirming
obstruction from an enlarged prostate is to pass a
special viewing instrument called a cystoscope into
the bladder, but this is not often necessary.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Drugs
A class of drugs called alpha-adrenergic blockers,
which includes phenoxybenzamine and doxazosin,
relax the muscle tissue surrounding the bladder outlet
and lining the wall of the urethra to permit urine to
flow more freely. These drugs improve obstructive
symptoms, but do not keep the prostate from enlarging. Other drugs (finasteride is a good example) do
shrink the prostate and may delay the need for surgery. Symptoms may not, however, improve until the
drug has been used for three months or longer.
Antibiotic drugs are given promptly whenever infection is diagnosed. Some medications, including antihistamines and some decongestants, can make the
symptoms of BPH suddenly worse and even cause
acute urinary retention, and therefore should be
avoided.

instrument or a heated wire loop. The small pieces of
prostate tissue are washed out through the scope. No
incision is needed for TUR. There normally is some
blood in the urine for a few days following the procedure. In a few men—less than 5% of all those having
TUR—urine will continue to escape unintentionally.
Other uncommon complications include a temporary
rise in blood pressure with mental confusion, which is
treated by giving salt solution. Impotence—the inability to achieve lasting penile erections—does occur, but
probably in fewer than 10% of patients. A narrowing
or stricture rarely develops in the urethra, but this can
be treated fairly easily.
Alternatives to TUR, some only recently introduced, include:


Laser ablation of the prostate. Laser energy is
applied to the prostate through a special fiber passed
through a cystoscope. The procedure is done in an
operating room, and several patients have retained
urine postoperatively.



Transurethral incision of the prostate. Less invasive
than standard TUR, an incision is made through the
prostate to open up the part of the urethra passing
through it. This may work well in men whose prostate is not grossly enlarged.



Transurethral vaporization. A small roller ball is
used to break up and vaporize the obstructing prostatic tissue, rather than cutting it away as in standard TUR. This is equally successful but patients
usually can leave the hospital within 24 hours, and
there is less blood loss.



If the prostate is greatly enlarged—as is the case in
about 5–10% of those diagnosed – an incision is
made to perform an open prostatectomy, removing
the entire gland under direct vision.

Intermediate treatments
When drugs have failed to control symptoms of
BPH but the physician does not believe that conventional surgery is yet needed, a procedure called
transurethral needle ablation may be tried. In the
office and using local anesthesia, a needle is inserted
into the prostate and radiofrequency energy is
applied to destroy the tissue that is obstructing
urine flow. Another new approach is microwave
hyperthermia, using a device called the Prostatron
to deliver microwave energy to the prostate through
a catheter. This procedure is done at an outpatient
surgery center.

Alternative treatment
An extract of the saw palmetto (Serenoa repens or
S. serrulata) has been shown to stop or decrease the
hyperplasia of the prostate. Symptoms of BPH will
improve after taking the herb for one to two months,
but continued use is recommended.

Prognosis
Surgery
For many years the standard operation for BPH
has been transurethral resection (TUR) of the prostate. Under general or spinal anesthesia, a cystoscope
is passed through the urethra and prostate tissue surrounding the urethra is removed using either a cutting
GALE ENCYCLOPEDIA OF MEDICINE

In a man without symptoms whose prostate is
enlarged, it is hard to predict when urinary symptoms
will develop and how rapidly they will progress. For
this reasons some specialists (urologists) advise a period of ‘‘watchful waiting.’’ When BPH is treated by
conventional TUR, there is a small risk of
1337

Enlarged prostate

It is routine to check a urine sample for an
increased number of white blood cells, which may
mean there is infection of the bladder or kidneys.
The same sample may be cultured to show what
type of bacterium is causing the infection, and
which antibiotics will work best. The state of the
kidneys may be checked in two ways: imaging by
either ultrasound or injecting a dye (the intravenous
urogram, or pyelogram); or a blood test for creatinine, which collects in the blood when the kidneys
cannot eliminate it.

Enterobacterial infections

Resources

KEY TERMS
Catheter—A rubber or plastic tube placed through
the urethra into the bladder to remove excess urine
when the flow of urine is cut off, or to prevent
urinary infection.
Creatinine—One of the ‘‘waste’’ substances normally excreted by the kidneys into the urine. When
urine flow is slowed, creatinine may collect in the
blood and cause toxic effects.
Hyperplasia—A condition where cells, such as
those making up the prostate gland, rapidly divide
abnormally and cause the organ to become
enlarged.

ORGANIZATIONS

Prostate Health Council. American Foundation for
Urologic Disease. 1128 N. Charles St., Baltimore, MD
21201. (800) 242-AFUD.

David A. Cramer, MD

Entamoeba histolytica infection see
Amebiasis
Enteric fever see Typhoid fever
Enterically transmitted non-A non-B see
Hepatitis E

Hypertrophy—A technical term for enlargement,
as in BPH (benign prostatic hypertrophy).
Urethra—In males, the tube that conducts urine
from the bladder through the penis to the outside
of the body. When narrowed by an enlarging prostate, symptoms of BPH develop.
Urinary retention—The result of progressive
obstruction of the urethra by an enlarging prostate,
causing urine to remain in the bladder even after
urination.

complications but, in the great majority of men, urinary symptoms will be relieved and their quality of life
will be much enhanced. In the future, it is possible that
the less invasive forms of surgical treatment will be
increasingly used to achieve results as good as those of
the standard operation. It also is possible that new
medications will be developed that shrink the prostate
and eliminate obstructive symptoms so that surgery
can be avoided altogether.

Prevention
Whether or not BPH is caused by hormonal
changes in aging men, there is no known way of preventing it. Once it does develop and symptoms are
present that interfere seriously with the patient’s life,
timely medical or surgical treatment will reliably prevent symptoms from getting worse. Also, if the condition is treated before the prostate has become grossly
enlarged, the risk of complications is minimal. One of
the potentially most serious complications of BPH,
urinary infection (and possible infection of the kidneys), can be prevented by using a catheter to drain
excess urine out of the bladder so that it does not
collect, stagnate, and become infected.
1338

Enterobacterial infections
Definition
Enterobacterial infections are disorders of the
digestive tract and other organ systems produced by
a group of gram-negative, rod-shaped bacteria called
Enterobacteriaceae. Gram-negative means that the
organisms do not retain the violet color of the dye
used to make Gram stains. The most troublesome
organism in this group is Escherichia coli. Other
enterobacteria are species of Salmonella, Shigella,
Klebsiella, Enterobacter, Serratia, Proteus, and
Yersinia.

Description
Enterobacterial infections can be produced by
bacteria that normally live in the human digestive
tract without causing serious disease, or by bacteria
that enter from the outside. In many cases these infections are nosocomial, which means that they can be
acquired in the hospital. Klebsiella and Proteus sometimes cause pneumonia, ear and sinus infections, and
urinary tract infections. Enterobacter and Serratia
often cause bacterial infection of the blood (bacteremia), particularly in patients with weakened immune
systems.
Diarrhea caused by enterobacteria is a common
problem in the United States. It is estimated that each
person in the general population has an average of 1.5
episodes of diarrhea each year, with higher rates in
children, institutionalized people, and Native
Americans. This type of enterobacterial infection can
range from a minor nuisance to a life-threatening disorder, especially in infants, elderly persons, AIDS
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Causes
Enterobacterial infections in the digestive tract
typically start when the organisms invade the mucous
tissues that line the digestive tract. They may be bacteria that are already present in the stomach and intestines, or they may be transmitted by contaminated
food and water. It is also possible for enterobacterial
infections to spread by person-to-person contact. The
usual incubation period is 12–72 hours.
ESCHERICHIA COLI INFECTIONS. E. coli infections
cause most of the enterobacterial infections in the
United States. The organisms are categorized according to whether they are invasive or noninvasive.
Noninvasive types of E. coli include what are called
enteropathogenic E. coli, or EPEC, and enterotoxigenic E. coli, or ETEC. EPEC and ETEC types produce a bacterial poison (toxin) in the stomach that
interacts with the digestive juices and causes the
patient to lose large amounts of water through the
intestines.

The invasive types of E. coli are called enterohemorrhagic E. coli, or EHEC, and enteroinvasive E.
coli, or EIEC. These subtypes invade the stomach
tissues directly, causing tissue destruction and bloody
stools. EHEC can produce complications leading to
hemolytic-uremic syndrome (HUS), a potentially fatal
disorder marked by the destruction of red blood cells
and kidney failure. EHEC has become a growing problem in the United States because of outbreaks caused
by contaminated food. A particular type of EHEC
known as O157:H7 has been identified since 1982 in
undercooked hamburgers, unpasteurized milk, and
apple juice. Between 2–7% of infections caused by
O157:H7 develop into HUS.
Symptoms
The symptoms of enterobacterial infections are
sometimes classified according to the type of diarrhea
they produce.
WATERY DIARRHEA. Patients infected with ETEC,
EPEC, some types of Salmonella, and some types of
Shigella develop a watery diarrhea. These infections
are located in the small intestine, result from bacterial
toxins interacting with digestive juices, do not produce
inflammation; and do not usually need treatment with
antibiotics.

GALE ENCYCLOPEDIA OF MEDICINE

BLOODY DIARRHEA (DYSENTERY). Bloody diarrhea
is sometimes called dysentery. It is produced by
EHEC, EIEC, some types of Salmonella, some types
of Shigella, and Yersinia. In dysentery, the infection is
located in the colon, cells and tissues are destroyed,
inflammation is present, and antibiotic therapy is
usually required.
NECROTIZING ENTEROCOLITIS (NEC). Necrotizing
enterocolitis (NEC) is a disorder that begins in newborn infants shortly after birth. Although NEC is not
yet fully understood, it is thought that it results from a
bacterial or viral invasion of damaged intestinal tissues. The disease organisms then cause the death
(necrosis) of bowel tissue or gangrene of the bowel.
NEC is primarily a disease of prematurity; 60–80% of
cases occur in high-risk preterm infants. NEC is
responsible for 2–5% of cases in newborn intensive
care units (NICU). Enterobacteriaceae that have been
identified in infants with NEC include Salmonella, E.
coli, Klebsiella, and Enterobacter.

Diagnosis
Patient history
The diagnosis of enterobacterial infections is complicated by the fact that viruses, protozoa, and other
types of bacteria can also cause diarrhea. In most cases
of mild diarrhea, it is not critical to identify the organism
because the disorder is self-limiting. Some groups of
patients, however, should have stool tests. They include:


patients with bloody diarrhea,



patients with watery diarrhea who have become
dehydrated,



patients with watery diarrhea that has lasted longer
than three days without decreasing in amount,



patients with disorders of the immune system.

The patient history is useful for public health
reasons as well as helping the doctor determine what
type of enterobacterium may be causing the infection.
The doctor will ask about the frequency and appearance of the diarrhea as well as other digestive symptoms. If the patient is nauseated and vomiting, the
infection is more likely to be located in the small
intestine. If the patient is running a fever, a diagnosis
of dysentery is more likely. The doctor will also ask if
anyone else in the patient’s family or workplace is sick.
Some types of enterobacteriaceae are more likely to
cause group outbreaks than others. Other questions
include the patient’s food intake over the last few days
and whether he or she has recently traveled to countries with typhoid fever or cholera outbreaks.
1339

Enterobacterial infections

patients, and malnourished people. Enterobacterial
infections are one of the two leading killers of children
in developing countries.

Enterobacterial infections

Physical examination
The most important parts of the physical examination are checking for signs of severe fluid loss and
examining the abdomen to rule out typhoid fever. The
doctor will look at the inside of the patient’s mouth
and evaluate the skin for signs of dehydration. The
presence of a skin rash and an enlarged spleen suggests
typhoid rather than a bacterial infection. If the
patient’s abdomen hurts when the doctor examines
it, a diagnosis of dysentery is more likely.
Laboratory tests
The most common test that is used to identify the
cause of diarrhea is the stool test. Examining a stool
sample under a microscope can help to rule out parasitic and protozoal infections. Routine stool cultures,
however, cannot be used to identify any of the four
types of E. coli that cause intestinal infections. ETEC,
EPEC, and EIEC are unusual in the United States and
can usually be identified only by specialists in research
laboratories. Because of concern about EHEC outbreaks, however, most laboratories in the United
States can now screen for O157:H7 with a test that
identifies its characteristic toxin. All patients with
bloody diarrhea should have a stool sample tested
for E. coli O157:H7.

Treatment
The initial treatment of enterobacterial diarrhea is
usually empiric. Empiric means that the doctor treats
the patient on the basis of the visible symptoms and
professional experience in treating infections, without
waiting for laboratory test results. Since the results of
stool cultures can take as long as two days, it is important to prevent dehydration. The patient will be given
fluids to restore the electrolyte balance and paregoric
to relieve abdominal cramping.
Newborn infants and patients with immune system disorders will be given antibiotics intravenously
once the organism has been identified. Gentamicin,
tobramycin, and amikacin are being used more frequently to treat enterobacterial infections because
many of the organisms are becoming resistant to
ampicillin and cephalosporin antibiotics.

KEY TERMS
Dysentery—A type of diarrhea caused by infection
and characterized by mucus and blood in the
stools.
Empirical treatment—Medical treatment that is
given on the basis of the doctor’s observations and
experience.
Escherichia coli—A type of enterobacterium that
is responsible for most cases of severe bacterial
diarrhea in the United States.
Hemolytic-uremic syndrome (HUS)—A potentially fatal complication of E. coli infections characterized by kidney failure and destruction of red
blood cells.
Necrotizing enterocolitis (NEC)—A disorder in
newborns caused by bacterial or viral invasion of
vulnerable intestinal tissues.
Nosocomial infections—Infections acquired in
hospitals.
Toxin—A poison produced by certain types of
bacteria.

Herbal medicine
Herbalists may recommend cloves taken as an
infusion or ginger given in drop doses to control intestinal cramps, eliminate gas, and prevent vomiting.
Peppermint (Mentha piperita) or chamomile
(Matricaria recutita) tea may also ease cramps and
intestinal spasms.
Homeopathy
Homeopathic practitioners frequently recommend Arsenicum album for diarrhea caused by contaminated food, and Belladonna for diarrhea that
comes on suddenly with mucus in the stools.
Veratrum album would be given for watery diarrhea,
and Podophyllum for diarrhea with few other
symptoms.

Prognosis
Alternative treatment
Alternative treatments for diarrhea are intended
to relieve the discomfort of abdominal cramping.
Most alternative practitioners advise consulting a
medical doctor if the patient has sunken eyes, dry
eyes or mouth, or other signs of dehydration.
1340

The prognosis for most enterobacterial infections
is good; most patients recover in about a week or 10
days without needing antibiotics. HUS, on the other
hand, has a mortality rate of 3–5% even with intensive
care. About a third of the survivors have long-term
problems with kidney function, and another 8%
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
The World Health Organization (WHO) offers
the following suggestions for preventing enterobacterial infections, including E. coli O157:H7 dysentery:


Cook ground beef or hamburgers until the meat is
thoroughly done. Juices from the meat should be
completely clear, not pink or red. All parts of the
meat should reach a temperature of 708C (1588F) or
higher.



Do not drink unpasteurized milk or use products
made from raw milk.



Wash hands thoroughly and frequently, especially
after using the toilet.



Wash fruits and vegetables carefully, or peel them.
Keep all kitchen surfaces and serving utensils clean.



If drinking water is not known to be safe, boil it or
drink bottled water.



Keep cooked foods separate from raw foods, and
avoid touching cooked foods with knives or other
utensils that have been used with raw meat.

Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Rebecca J. Frey, PhD

Enterobiasis
Definition
Enterobiasis, or pinworm infection as it is commonly
called, is an intestinal infection caused by the parasitic
roundworm called Enterobius vermicularis. The most
common symptom of this irritating, but not particularly
dangerous, disease is itching around the anal area.

Description
Enterobiasis is also called seatworm infection or
oxyuriasis. In the United States, enterobiasis is the
most common worm infection, and some estimate
that approximately 10% of the United States
GALE ENCYCLOPEDIA OF MEDICINE

population is infected. Worldwide, approximately
200 million people are infected. Enterobiasis can affect
people of any age, but is most common among children ages 5–14 and particularly affects those in the
daycare setting.

Causes and symptoms
The disease is highly contagious and is caused by a
parasitic worm called Enterobius vermicularis. The adult
female worm is about the size of a staple (approximately
0.4 in [1 cm long] and 0.02 in [0.5 mm] wide) and has a
pointed tip. The disease is transmitted by ingesting the
eggs of the pinworm. These eggs travel to the small intestine where, after approximately one month, they hatch
and mature into adult worms. During the night, the
female adult worms travel to the area around the anus
and deposit eggs in the folds of the anal area. A single
female pinworm can lay 10,000 eggs and, after laying
eggs, dies. The eggs are capable of causing infection
after six hours at body temperature.
Significant itching in the anal region is caused by
the movement of the adult worm as the eggs are
deposited. When an individual scratches the anal
region, the tiny eggs get under the finger nails and in
the underwear and night clothes. Anything the individual touches with the contaminated fingers, for example, toys, bedding, blankets, bathroom door knobs, or
sinks, becomes contaminated. The eggs are very hardy
and can live on surfaces for two to three weeks.
Anyone touching these contaminated surfaces can
ingest the eggs and become infected. An individual
can also become infected by inhaling and swallowing
the eggs, for example, when the bedcovers are shaken.
Many individuals with enterobiasis exhibit no
symptoms. When present, however, symptoms of the
infection begin approximately two weeks after ingesting the pinworm eggs. The main symptom is itching
around the anus. Because the itching intensifies at
night, when the female worms comes to the anus to
lay eggs, it often leads to disrupted sleep and irritability. Poor sleeping at night in small children can be
related to pinworms. Occasionally, the itching causes
some bleeding and bruising in the region, and secondary bacterial infections can occur. In females, the itching may spread to the vagina and sometimes causes an
infection of the vaginal region (vaginitis). Enterobiasis
usually lasts one to two months.

Diagnosis
First, a physician will rule out other potential
causes of the itching, such as hemorrhoids, lice, or
1341

Enterobiasis

develop high blood pressure, seizure disorders, and
blindness.

Enterobiasis

KEY TERMS
Anus—The opening through which feces are
eliminated.
Hemorrhoid—An area around the anus where
veins become dilated and the tissue swells, causing
itching and pain.
Rectum—The end of the large intestine in which
feces collects for elimination through the anus.
Vaginitis—Inflammation of the vagina.

The pinworm of the genus Enterobius pictured above is the
source of this infestation occurring in children. (Photo
Researchers, Inc. Reproduced by permission.)

fungal or bacterial infection. Once these have been
ruled out, an accurate diagnosis of enterobiasis will
require that either the eggs or the adult worms are
detected. Rarely, the adult worms are seen as thin,
yellowish-white threads, about 0.4 in (1 cm) long,
in the stools of the infected person. Usually, an
hour or so after the individual goes to sleep,
the adult female worms may be seen moving
around laying eggs if a flashlight is shone at the
rectal area.
An easier method is to observe the eggs under
the microscope. In order to collect a specimen for
laboratory diagnosis, the physician may provide a
paddle with a sticky adhesive on one side, or an
individual may be instructed to place a piece of
shiny cellophane tape sticky side down against the
anal opening. The best time to perform this test is
at night or as soon as the individual wakes up in
the morning, before having a bowel movement or
taking a bath or shower. The pinworm eggs will
stick to the tape, which can then be placed on a
specimen slide. When under a microscope in the
laboratory, the eggs will be clearly visible.

Treatment
In order to treat the disease, either mebendazole (Vermox) or pyrantel pamoate (Pin-X) will be
given in two oral doses spaced two weeks apart.
These medications eradicate the infection in
approximately 90% of cases. Re-infection is common and several treatments may be required.
Because the infection is easily spread through contact with contaminated clothing or surfaces, it is
recommended that all family members receive the
therapeutic dose. Sometimes a series of six
1342

treatments are given, each spaced two weeks
apart. If family members continue to be infected,
a source outside the house may be responsible.
To relieve the rectal itching, a shallow warm bath
with either half a cup of table salt, or Epsom salts is
recommended. Also, application of an ointment containing zinc oxide or regular petroleum jelly can be
used to relieve rectal itching.

Prognosis
Pinworms cause little damage and can be easily
eradicated with proper treatment. Full recovery is
expected.

Prevention
The disease can be prevented by treating all the
infected cases and thus eliminating the source of
infection. Some ways to keep from catching or
spreading the disease include the following
recommendations:


wash hands thoroughly before handling food and
eating



keep finger nails short and clean



avoiding scratching the anal area



take early morning showers to wash away eggs
deposited overnight



once the infection has been identified, and treatment
is started, change the bed linen, night clothes, and
underwear daily



machine wash linens in hot water and dry with heat
to kill any eggs



open the blinds or curtains since eggs are sensitive to
sunlight
GALE ENCYCLOPEDIA OF MEDICINE



Removal of diseased sections of the intestines.
Ileostomies performed for this reason are permanent. The most common disorders requiring permanent ileostomy are Crohn’s disease, familial polyposis,
and ulcerative colitis. Familial polyposis and ulcerative colitis are serious health risks because they can
develop into cancer.



Treatment of advanced cancer or other causes of
intestinal obstruction.

BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

Lata Cherath, PhD

Enterohemorrhagic E. coli see Escherichia coli

Precautions

Enterostomy
Definition
An enterostomy is an operation in which the surgeon makes a passage into the patient’s small intestine
through the abdomen with an opening to allow for
drainage or to insert a tube for feeding. The opening is
called a stoma, from the Greek word for mouth.
Enterostomies may be either temporary or permanent.
They are classified according to the part of the intestine that is used to create the stoma. If the ileum, which
is the lowest of the three sections of the small intestine,
is used to make the stoma, the operation is called an
ileostomy. If the jejunum, which is the middle section
of the small intestine, is used, the operation is called a
jejunostomy. Some people use the word ostomy as a
word that covers all types of enterostomies.

Purpose
Enterostomies are performed in order to create a
new opening for the passage of fecal matter when
normal intestinal functioning is interrupted or when
diseases of the intestines cannot be treated by medications or less radical surgery. Some situations that may
require enterostomies include:


Healing of inflamed bowel segments. Enterostomies
performed for this reason are usually temporary.



Emergency treatment of gunshot or other penetrating wounds of the abdomen. An enterostomy is
needed to prevent the contents of the intestine from
causing a serious inflammation of the inside of the
abdominal cavity (peritonitis). These enterostomies
are also often temporary.



Placement of a tube for enteral feeding. Enteral feeding is a method for conveying nutritional solutions
directly into the stomach or jejunum through a tube.
Tube enterostomies may be long-term but are not
permanent.

GALE ENCYCLOPEDIA OF MEDICINE

Enterostomies are usually performed only as emergency treatments for traumatic injuries in the abdomen
or as final measures for serious disorders of the intestines. Most patients do not refuse to have the operation
performed when the need for it is explained to them. A
small minority, however, refuse enterostomies because
of strong psychological reactions to personal disfigurement and the need to relearn bowel habits.

Description
Ileostomy
Ileostomies represent about 25% of enterostomies. They are performed after the surgeon removes
a diseased colon and sometimes the rectum as well.
The most common ileostomy is called a Brooke ileostomy after the English surgeon who developed it. In a
Brooke ileostomy, the surgeon makes the stoma in the
lower right section of the abdomen. The ileum is pulled
through an opening (incision) in the muscle layer. The
surgeon then turns the cut end of the intestine inside
out and sews it to the edges of the hole. He or she then
positions an appliance for collecting the fecal material.
The appliance consists of a plastic bag that fits over the
stoma and lies flat against the abdomen. The patient is
taught to drain the bag from time to time during the
day. Ileostomies need to be emptied frequently
because the digested food contains large amounts of
water. Shortly after the operation, the ileostomy produces 1–2 qt.(0.9–1.9 l) of fluid per day; after a month
or two of adjustment, the volume decreases to 1–2 pt
(0.5–0.9) per day.
KOCK POUCH (CONTINENT ILEOSTOMY). The Kock
pouch is a variation of the basic ileostomy and is
named for its Swedish inventor. In the Kock technique, the surgeon forms a pouch inside the abdominal
cavity behind the stoma that collects the fecal material.
The stoma is shaped into a valve to prevent fluid from
leaking onto the patient’s abdomen. The patient then
empties the pouch several times daily by inserting a
tube (catheter) through the valve. The Kock technique

1343

Enterostomy

Resources

Enterostomy

is sometimes called a continent ileostomy because the
fluid is contained inside the abdomen. It is successful
in 70–90% of patients who have it done.
Jejunostomy
A jejunostomy is similar to an ileostomy except
that the stoma is placed in the second section of the
small intestine rather than the third. Jejunostomies are
performed less frequently than ileostomies. They are
almost always temporary procedures.
Tube enterostomies
Tube enterostomies are operations in which the
surgeon makes a stoma into the stomach itself or the
jejunum in order to insert a tube for liquid nutrients.
Tube enterostomies are performed in patients who
need tube feeding for longer than six weeks, or who
have had recent mouth or nose surgery. As long as the
patient’s intestinal tract can function, tube feedings
are considered preferable to intravenous feeding.
Enteral nutrition is safer than intravenous fluids and
helps to keep the patient’s digestive tract functioning.

Preparation
Preoperative preparation includes both patient
education and physical preparation.
Patient education
If the patient is going to have a permanent ileostomy, the doctor will explain what will happen during
the operation and why it is necessary. Most patients
are willing to accept an ostomy as an alternative to the
chronic pain and diarrhea of ulcerative colitis or the
risk of cancer from other intestinal disorders. The
patient can also meet with an enterostomal therapist
(ET) or a member of the United Ostomy Association,
which is a support group for people with ostomies.

Medical aftercare
If the enterostomy is temporary, aftercare consists of the usual monitoring of surgical wounds for
infection or bleeding. If the patient has had a permanent ileostomy, aftercare includes learning to use the
appliance or empty the Kock pouch; learning to keep
the stoma clean; and readjusting bathroom habits.
Recovery takes a long time because major surgery is
a shock to the system and the intestines take several
days to resume normal functioning. The patient’s
fluid intake and output will be checked frequently
to minimize the risk of dehydration.
Patient education
Ileostomy patients must learn to watch their fluid
and salt intake. They are at greater risk of becoming
dehydrated in hot weather, from exercise, or from
diarrhea. In some cases they may need extra bananas
or orange juice in the diet to keep up the level of
potassium in the blood.
Patient education includes social concerns as
well as physical self-care. Many ileostomy patients
are worried about the effects of the operation on
their close relationships and employment. If the
patient has not seen an ET before the operation,
the aftercare period is a good time to find out
about self-help and support groups. The ET can
also evaluate the patient’s emotional reactions to
the ostomy.

Risks
Enterostomies are not considered high-risk operations by themselves. About 40% of ileostomy patients
have complications afterward, however; about 15%
require minor surgical corrections. Possible complications include:


skin irritation caused by leakage of digestive fluids
onto the skin around the stoma; Irritation is the most
common complication of ileostomies



diarrhea



the development of abscesses



gallstones or stones in the urinary tract



inflammation of the ileum



odors can often be prevented by a change in diet



intestinal obstruction



a section of the bowel pushing out of the body
(prolapse)

Medical preparation
The patient is prepared for surgery with an evaluation of his or her nutritional status, possible need
for blood transfusions, and antibiotics if necessary. If
the patient does not have an intestinal obstruction or
severe inflammation, he or she may be given a large
quantity of a polyethylene glycol (PEG) solution to
cleanse the intestines before surgery.

Aftercare
Aftercare of an enterostomy is both psychological
and medical.
1344

GALE ENCYCLOPEDIA OF MEDICINE

Crohn’s disease—A disease of the intestines that
causes inflammation leading to scarring, thickening of the walls of the intestine, and eventual
obstruction.
Duodenum—The first of the three segments of the
small intestine. The duodenum connects the
stomach and the jejunum.
Enteral nutrition—A technique for feeding patients
with liquid formulas conveyed directly into the
stomach or jejunum through tubes.
Enterostomal therapist (ET)—A specialized counselor, usually a registered nurse, who provides
ostomy patients with education and counseling
before the operation. After surgery, the ET helps
the patient learn to take care of the stoma and
appliance, and offers long-term emotional support.
Familial polyposis—A disease that runs in families
in which lumps of tissue (polyps) form inside the
colon. Familial polyposis may develop into cancer.
Ileum—The third segment of the small intestine,
connecting the jejunum and the large intestine.
Jejunum—The second of the three segments of the
small intestine, connecting the duodenum and the
ileum.
Kock pouch—A type of ileostomy in which the
surgeon forms an artificial rectum from a section
of the ileum. A Kock pouch is sometimes called
a continent ileostomy because it is drained with a
tube.
Ostomy—A common term for all types of
enterostomies.
Stoma—The surgically constructed mouth or
passage between the intestine and the outside of
the patient’s body.
Tube enterostomy—An enterostomy performed to
allow the insertion of a feeding tube into the
jejunum or stomach.
Ulcerative colitis—A disease of the colon characterized by inflammation of the mucous lining,
ulcerated areas of tissue, and bloody diarrhea.

Normal results
Normal results include recovery from the surgery
with few or no complications. About 95% of people
with ostomies recover completely, are able to return to
work, and consider themselves to be in good health.
GALE ENCYCLOPEDIA OF MEDICINE

Many ileostomy patients enjoy being able to eat a
full range of foods rather than living on a restricted
diet. Some patients, however, need to be referred to
psychotherapists to deal with depression or other
emotional problems after the operation.
Resources
ORGANIZATIONS

United Ostomy Association, Inc. (UOA). 19772 MacArthur
Blvd., Suite 200, Irvine, CA 92612-2405. (800)
826-0826. <http://www.uoa.org>.

Rebecca J. Frey, PhD

Enterovirus infections
Definition
Enteroviruses are so named because they reproduce initially in the gastrointestinal tract after infection occurs. Despite, this, they usually do not lead to
intestinal symptoms; rather it is their spread to organs,
such as the nervous system, heart, skin, and others that
causes disease. Enteroviruses are part of a larger group
of viruses known as Picornaviruses. The word comes
from the combination of ‘‘pico’’ (Spanish, meaning ‘‘a
little bit’’), and RNA (ribonucleic acid, an important
component of genetic material).

Description
There are four groups of enteroviruses:
Coxsackievirus, Echovirus, ungrouped Enterovirus,
and Y Poliovirus.
Viruses are generally divided into those that use
DNA (deoxyribonucleic acid) or RNA as their genetic
material; all enteroviruses are RNA viruses. They are
found worldwide, but infection is more common in
areas of poor hygiene and overcrowding.
Although most cases of enterovirus do not produce symptoms, some five to 10 million individuals in
the United States each year suffer from one of the
enteroviral diseases. Illness is more common in the
very young. While there are close to 70 different
strains of enteroviruses, over 70% of infections are
caused by only 10 types.
The virus is most commonly transmitted by the
fecal-oral route (contamination of fingers or objects
by human waste material); in some instances transmission is through contaminated food or water.
1345

Enterovirus infections

KEY TERMS

Enterovirus infections

Passage of some strains of virus by way of air droplets
can lead to respiratory illness. Infection of fetuses by
way of the placenta also has been documented. Breast
milk contains antibodies which can protect
newborns.
The incubation period for most enteroviruses
ranges from two to 14 days. In areas of temperate
climate, infections occur mainly in the summer and fall.

tissue itself, producing encephalitis. The illness
resolves after about a week or so, and permanent
damage is unusual. Enteroviruses can also produce
the Guillian-Barré syndrome, which involves weakness and paralysis of the extremities and even the
muscles of respiration.


Pleurodynia (Bornholm’s disease) is due to viral
infection and inflammation of the chest and abdominal muscles used for breathing. Pain occurs as acute
episodes, lasting 30 minutes or so. Coxsackie B virus
is the usual cause of the illness.



Myocarditis and/or pericarditis involves infection
of the heart muscle (myocardium) and the covering
around the heart (pericardium). Infants and young
adults are the most susceptible, and for some reason, more than two-thirds of cases occur in males.
The disease usually begins as an upper respiratory
tract infection with cough, shortness of breath, and
fever. Chest pain, increasing shortness of breath,
irregularities of cardiac rhythm, and heart failure
sometimes develop. Some patients wind up with
long-term heart failure if the heart muscle is significantly affected.



Exanthems is the medical term for rashes, and enterovirus is the number one cause of summer and fall
rashes in children. They occur anywhere on the body,
and often resemble diseases such as measles.



Hand-foot-and-mouth disease occurs initially as a
sore throat (often involving the tongue as well), and
is followed by a rash on the hands, and sometimes the
feet. The rash often forms small blisters, which lead
to ulcers. Symptoms generally resolve within a week.
A specific Coxsackievirus (A16) is the most frequent
cause of this highly infectious disease.



Herpangina is most often caused by one of the
Coxsackie A viruses, and appears as the acute onset
of fever and sore throat. This last symptom is particularly severe, as the virus produces multiple ulcers
in the throat. Swallowing becomes very painful;
symptoms can persist for several weeks.



Acute hemorrhagic conjunctivitis involves viral
infection of the conjunctiva, which is a covering
around the eye. Pain, blurred vision, aversion to
light, and a discharge from the eye are the main
symptoms. Headache and fever occur in about one
in five patients. The disease runs its course in about
10 days.

Causes and symptoms
Enteroviruses are believed to be the cause of at
least 10 distinct illnesses. Once they enter the body,
they multiply in the cells that line the gastrointestinal
tract, and eventually reach sites of lymphatic tissue
(such as the tonsils). While most of these diseases are
of short duration and do not cause significant injury,
some can produce severe illness. Each presents its own
unique symptoms. And a 2003 report to the Infectious
Diseases Society of America reminded physicians that
infants with enteroviral infections often present early
in their illnesses with no signs of fever, complicating
diagnosis.
The main syndromes caused by the various enteroviruses are the following:






Summer grippe (nonspecific febrile illness). This is
the most common syndrome, and is characterized by
flu-like symptoms of fever, headache, and weakness,
that typically last three to four days. Many patients
also develop upper respiratory symptoms and some
nausea and vomiting. One of the major ways to
distinguish this disease from influenza, is the fact
that grippe most often occurs in the summer.
Generalized disease of the newborn is a potentially
serious infection in which infants from one week to
three months of age develop a syndrome that can be
difficult to distinguish from a severe bacterial infection. Fever, irritability, and decreased responsiveness
or excessive sleepiness are the major symptoms.
Inflammation of heart muscle (myocarditis), low
blood pressure, hepatitis, and meningitis sometimes
complicate the illness.
Aseptic meningitis encephalitis is a well known syndrome caused by this group of viruses. In fact, enteroviruses are responsible for over 90% of cases of
aseptic meningitis, and most often hit children and
young adults. Headache, fever, avoidance of light,
and eye pain are characteristic. Drowsiness may be
prominent, and other symptoms include sore throat,
cough, muscle pain, and rash. Occasionally, not only
the meninges;mdash;the covering around the brain
and spinal cord;mdash;is infected, but also brain

1346

A number of other illnesses have been attributed
to enteroviruses, including pneumonia and other
respiratory infections, myositis or muscle inflammation, arthritis, and acute inflammation of the kidneys.
GALE ENCYCLOPEDIA OF MEDICINE

Antibodies—Proteins that are formed by the body
and play a role in defense against infection.
Antibiotic—A medication that is designed to kill or
weaken bacteria.
Meninges—Outer covering of the spinal cord and
brain. Infection is called meningitis, which can lead
to damage to the brain or spinal cord and lead to
death.

It is clear then that these viruses produce a number of
various illnesses, most often in younger age groups.

(hypogammaglobunemia), administrating antibodies
themselves is helpful.

Prognosis
The overall outlook for enterovirus infection
depends on the organs involved, and the immune
condition of the individual patient. Unless vital
organs are involved or immunity is abnormal, infection causes few problems. On the other hand,
patients who have diseases that affect antibody production can develop chronic infection of the brain
or meninges. A 2003 study found that enterovirus
infections can increase the risk of type 1 diabetes
in children who are genetically predisposed to
diabetes.

Prevention
Diagnosis
In the majority of cases, diagnosis is based on the
characteristic symptoms that the virus produces (such
as the chest pain in pleurodynia). Rarely is it necessary
to identify a specific strain of virus causing the illness.
It is more important to be certain that the infection is
due to a virus that does not require treatment with
antibiotics.
Culture, or growing the organism outside of the
body, is helpful only when obtained from areas that
tend to indicate recent infection, such as from swollen
joints, cerebrospinal fluid, or blood. Cultures from
other areas, such as the throat, can be misleading.
This is because the virus may remain for long periods
of time in places with a large amount of lymphatic
tissue. As a rule, cultures done early in the illness are
more likely to identify the virus.
New techniques that involve identification of viral
genetic material (PCR) are useful in certain cases, but
are not indicated for routine testing.

Treatment
As noted above, enterovirus is capable of attacking many different organs and producing a variety of
symptoms. Most infections are mild and improve
without complications, requiring no specific therapy.
When the virus attacks critical organs however, such
as the heart, respiratory muscles, nervous system, etc.,
specialized care is often needed.
As of 2001, no effective antiviral medication for
enterovirus has undergone investigation in patients,
though some drugs appeared promising for the future.
In some patients who are unable to produce antibodies
GALE ENCYCLOPEDIA OF MEDICINE

In the hospital setting, the best means of avoiding
transmission of infection is the use of good handwashing practices and other appropriate precautions
(gowns and gloves for hospital staff). The virus is
found in feces for up to one week after infection;
therefore precautions that isolate waste material
(enteric precautions) will help decrease the chance of
spreading the illness.
Resources
PERIODICALS

‘‘Enterovirus Infections Increase Risk of Type 1 Diabetes in
High-Risk Children.’’ Diabetes Week June 16, 2003: 22.
Tucker, Miriam E. ‘‘Fever Often Absent in Early
Enteroviral Illness (Severe Cases).’’ Pediatric News
January 2003: 20–22.
OTHER

‘‘Hand, Foot and Mouth Disease.’’ The Picarnovirus Home
Page.<http://www.iah.bbsrc.ac.uk/virus/
Picornaviridae/picornavirus.htm>.
‘‘Weekly Clinicopathological Exercises: Case 47- 1993: A
28-Year-Old Man with Recurrent Ventricular
Tachycardia and Dysfunction of Multiple Organs.’’
New England Journal of Medicine Online. <http://
content.nejm.org>.

David Kaminstein, MD
Teresa G. Odle

Entropy see Eyelid disorders
Enuresis see Bed-wetting
Environmental medicine see Wilderness
medicine
1347

Enterovirus infections

KEY TERMS

Enzyme therapy

Enzyme therapy
Definition
Enyzme therapy is a plan of dietary supplements
of plant and animal enzymes used to facilitate the
digestive process and improve the body’s ability to
maintain balanced metabolism.

Purpose
In traditional medicine, enzyme supplements are
often prescribed for patients suffering from disorders
that affect the digestive process, such as cystic fibrosis,
Gaucher’s disease, and celiac disease. A program of
enzyme supplementation is rarely recommended for
healthy patients. However, proponents of enzyme therapy believe that such a program is beneficial for everyone. They point to enzymes’ ability to purify the blood,
strengthen the immune system, enhance mental capacity,
cleanse the colon, and maintain proper pH balance in
urine. They feel that by improving the digestive process,
the body is better able to combat infection and disease.
Some evidence exists that pancreatic enzymes
derived from animal sources are helpful in cancer
treatment. The enzymes may be able to dissolve the
coating on cancer cells and may make it easier for the
immune system to attack the cancer.
A partial list of the wide variety of complaints and
illnesses that can be treated by enzyme therapy includes:



hepatitis



hypoglycemia



infections



mucous congestion



multiple sclerosis



nervous disorders



nutritional disorders



obesity



premenstrual syndrome (PMS)



stress

Description
Origins
Enzymes are protein molecules used by the body
to perform all of its chemical actions and reactions.
The body manufactures several thousands of enzymes.
Among them are the digestive enzymes produced by
the stomach, pancreas, small intestine, and the salivary glands of the mouth. Their energy-producing
properties are responsible for not only the digestion
of nutrients, but their absorption, transportation,
metabolization, and elimination as well.
Enzyme therapy is based on the work of Dr.
Edward Howell in the 1920s and 1930s. Howell proposed that enzymes from foods work in the stomach to
pre-digest food. He advocated the consumption of
large amounts of plant enzymes, theorizing that if the
body had to use less of its own enzymes for digestion, it
could store them for maintaining metabolic harmony.
Four categories of plant enzymes are helpful in predigestion: protease, amylase, lipase, and cellulase.
Cellulase is particularly helpful because the body is
unable to produce it.



AIDS



anemia



alcohol consumption



anxiety



acute inflammation



back pain



cancer



colds



chronic fatigue syndrome



colitis

The seven categories of food enzymes and their
activities



constipation



amylase breaks down starches



diarrhea



cellulase breaks down fibers



food allergies



lactase breaks down dairy products



gastritis



lipase breaks down fats



gastric duodenal ulcer



maltase breaks down grains



gout



protease breaks down proteins



headaches



sucrase breaks down sugars

1348

Animal enzymes, such as pepsin extracted from
the stomach of pigs, work more effectively in the duodenum. They are typically used for the treatment of
nondigestive ailments.

GALE ENCYCLOPEDIA OF MEDICINE

Enzyme supplements are extracted from plants
like pineapple and papaya and from the organs of
cows and pigs. The supplements are typically given in
tablet or capsule form. Pancreatic enzymes may also
be given by injection. The dosage varies with the condition being treated. For nondigestive ailments, the
supplements are taken in the hour before meals so
that they can be quickly absorbed into the blood.
For digestive ailments, the supplements are taken
immediately before meals accompanied by a large
glass of fluids. Pancreatic enzymes may be accompanied by doses of vitamin A.

Preparations
No special preparations are necessary before
beginning enzyme therapy. However, it is always advisable to talk to a doctor or pharmacist before purchasing enzymes and beginning therapy.

Precautions
People with allergies to beef, pork, pineapples, and
papaya may suffer allergic reactions to enzyme supplements. Tablets are often coated to prevent them from
breaking down in the stomach, and usually shouldn’t
be chewed or crushed. People who have difficulty
swallowing pills can request enzyme supplements in
capsule form. The capsules can then be opened and
the contents sprinkled onto soft foods like applesauce.

KEY TERMS
Celiac disease—A chronic disease characterized by
defective digestion and use of fats.
Cystic fibrosis—A genetic disease that causes
multiple digestive, excretion, and respiratory
complications. Among the effects, the pancreas
fails to provide secretions needed for the digestion
of food.
Duodenum—The first part of the small intestine.
Gaucher’s disease—A rare genetic disease caused
by a deficiency of enzymes needed for the processing of fatty acids.
Metabolism—The system of chemical processes
necessary for living cells to remain healthy.

enzymes can result in a build up of uric acid in the
blood or urine and can cause a break down of proteins.

Research and general acceptance
In the United States, the Food and Drug
Administration (FDA) has classified enzymes as a
food. Therefore, they can be purchased without a prescription. However, insurance coverage is usually
dependent upon the therapy resulting from a doctor’s
orders.
Resources
OTHER

Enzyme Therapy for Your Health. <http://members.tripod.com/~colloid/enzyme.htm>.
Questions and Answers about Food Enzymes and Nutrition.
<http://www.enzymes.com>.
Therapies: Enzyme Therapy. <http://library.thinkquest.org/24206/enzyme-therapy.html>.

Side effects
Side effects associated with enzyme therapy
include heartburn, nausea and vomiting, diarrhea,
bloating, gas, and acne. According to the principles
of therapy, these are temporary cleansing symptoms.
Drinking eight to 10 glasses of water daily and getting
regular exercise can reduce the discomfort of these
side effects. Individuals may also experience an
increase in bowel movements, perhaps one or two
per day. This is also considered a positive effect.
Plant enzymes are safe for pregnant women,
although they should always check with a doctor
before using enzymes. Pregnant women should avoid
animal enzymes. In rare cases, extremely high doses of
GALE ENCYCLOPEDIA OF MEDICINE

Mary McNulty

Eosinophilic granuloma see Histiocytosis X

Eosinophilic pneumonia
Definition
Eosinophilic pneumonia is a group of diseases in
which there is an above normal number of eosinophils
in the lungs and blood.
1349

Eosinophilic pneumonia

Enzyme theory generated further interest as the
human diet became more dependent on processed and
cooked foods. Enzymes are extremely sensitive to
heat, and temperatures above 1188F (488C) destroy
them. Modern processes of pasteurization, canning,
and microwaving are particularly harmful to the
enzymes in food.

Epidermolysis bullosa

Description
Eosinophilia is an increase in the number of
eosinophils. Eosinophilic pneumonia is characterized by a large number of eosinophils in the lungs,
usually in the absence of an infectious disease.
Eosinophils are one of the white blood cells and
are classified as a granulocyte. They are part of
the non-specific immune system and participate
in inflammatory reactions. Eosinophils contain
cationic molecules that are useful for destroying
infectious agents, especially heiminthic parasites
(worms). There are several types of eosinophilic
pneumonia. Loffler’s pneumonia is a temporary
infiltration of eosinophils into the lungs. The patient
will feel tired, have a cough, spasms of the bronchial
airway, and difficulty breathing. Loffler’s pneumonia will clear spontaneously, but slowly over the
course of about a month. Another form of eosinophilic pneumonia, pulmonary infiltrates with eosinophilia (PIE), is a more serious and potentially fatal
disease. In PIE, the patient experiences asthma,
pulmonary infiltrates, disorders of the peripheral
nervous system, central nervous systems symptoms,
and periarteritis nodosa.

Causes and symptoms
Pneumonia with eosinophils occurs as part of a
hypersensitivity reaction. A hypersensitivity reaction
is an over-reaction of the immune system to a particular
stimulus. As part of the hypersensitive reaction, cells of
the immune system are produced in increased numbers
and migrate into areas targeted by the hypersensitivity
reaction. In the case of eosinophilic pneumonia, the
lungs are the target. Generally, eosinophilia pneumonia
is not a reaction to an infection. There is a correlation
between asthma and eosinophilic pneumonia.
Eosinophilic pneumonia can also be caused by drugs
and, in some people, by polluted air. The symptoms
range from mild (coughing, wheezing, and shortness of
breath) to severe and life threatening (severe shortness
of breath and difficulty getting enough oxygen). The
symptoms may resolve spontaneously or can persist
for long periods of time. In a few cases, the disease
may rapidly produce life-threatening pneumonia.

KEY TERMS
Infiltrates—Cells or body fluids that have passed
into a tissue or body cavity.
Sputum—Material coughed up from the throat or
lungs.

(the eosinophils and fluid). If sputum is produced in
coughing, eosinophils will be seen instead of the more
normal profile of granulocytes seen when an infectious
agent is present.

Treatment
Eosinophilic pneumonia may not respond to
drugs used to treat asthma. Eosinophilic pneumonia
is usually treated with steroids, particularly glucocorticosteroids. Steroids are not effective against
infectious agents, but the main disease process in eosinophilic pneumonia is an inflammatory reaction, not a
response to infection. When eosinophilia is produced
as a consequence of asthma or an infection by
helminths, treatment of the asthma or helminths will
reduce the eosinophilia.
Resources
BOOKS

Berkow, Robert, editor. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

John T. Lohr, PhD

Ephedrine see Bronchodilators
Epicondylitis see Tennis elbow
Epidemic icterus see Hepatitis A
Epidemic typhus see Typhus
Epidemic viral gastroenteritis see Rotavirus
infections

Diagnosis
Since eosinophilia is common to a number of
conditions, the physician must rule out asthma and
infection by helminths when diagnosing eosinophilic
pneumonia. A whole blood count will reveal an
increased number of eosinophils in the blood. An x
ray of the lungs may show the presence of infiltrates
1350

Epidermolysis bullosa
Definition
Epidermolysis bullosa (EB) is a group of rare
inherited skin diseases that are characterized by
the development of blisters following minimal
GALE ENCYCLOPEDIA OF MEDICINE

Description
Epidermolysis bullosa has three major forms and
at least 16 subtypes. The three major forms are EB
simplex, junctional EB, and dystrophic EB. These
can range in severity from mild blistering to more
disfiguring and life-threatening disease. Physicians
diagnose the form of the disease based on where the
blister forms in relation to the epidermis (the skin’s
outermost layer) and the deeper dermis layer.
The prevalence of epidermolysis varies among
different populations. A study in Scotland estimated
the prevalence to be one in 20,400. Researchers in
other parts of the world estimate the prevalence to be
one in 100,000. This variance is due to the variability
of expression. Many cases of epidermolysis bullosa are
often not accurately diagnosed and thus, are not
reported.

Causes and symptoms
EB can be inherited as the result of a dominant
genetic abnormality (only one parent carries the
abnormal gene) or a recessive genetic abnormality
(both parents carry the abnormal gene).
EB simplex results from mutations in genes
responsible for keratin 5 and 14, which are proteins
that give cells of the epidermis its structure. EB
simplex is transmitted in an autosomal dominant
fashion.
Dystrophic EB is caused by mutations in genes for
type VII collagen, the protein contained in the fibers
anchoring the epidermis to the deeper layers of the
skin. The genetic mutations for junctional EB are
found in the genes responsible for producing the
protein Laminin-5. Dystrophic EB is an autosomal
disorder and will only result if both parents transmit
an abnormal gene during conception.
EB simplex, the most common form of EB, is the
least serious form of the disease. In most affected
individuals, the blisters are mild and do not scar after
they heal. Some forms of EB simplex affect just the
hands and feet. Other forms of EB simplex can lead to
more widespread blistering, as well as hair loss and
missing teeth. Recurrent blistering is annoying but not
life threatening.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Collagen—The main supportive protein of cartilage, connective tissue, tendon, skin, and bone.
Dermis—The layer of skin beneath the epidermis.
Epidermis—The outermost layer of the skin.
Keratin—A tough, nonwater-soluble protein found
in the nails, hair, and the outermost layer of skin.
Human hair is made up largely of keratin.

The second, or junctional, form of EB does not
lead to scarring. However, skin on the areas prone to
blistering, such as elbows and knees, often shrinks. In
one variation of junctional EB, called gravis junctional
EB of Herlitz, the blistering can be so severe that
affected infants may not survive due to massive
infection and dehydration.
The third form of EB, dystrophic EB, varies
greatly in terms of severity, but more typically affects
the arms and legs. In one variation, called HallopeauSiemens EB, repeated blistering and scarring of the
hands and feet causes the fingers and toes to fuse,
leaving them dysfunctional and with a mitten-like
appearance.

Diagnosis
Physicians and researchers distinguish between
the three major subtypes of EB based on which layer
of the epidermis separates from the deeper dermis
layer of the skin below. Patients suspected of having
EB should have a fresh blister biopsied for review.
This sample of tissue is examined under an electron
microscope or under a conventional microscope using
a technique called immunofluorescence, which helps
to map the underlying structure.
Knowing that a family member has EB can help
establish the diagnosis, but it is possible that parents
or siblings will show no sign of the disease, either
because it is caused by a new genetic mutation, or
because the parents are carriers of the recessive trait
and do not display the disease.

Treatment
The most important treatment for EB is daily
wound care. Because the skin is very fragile, care
must be taken to be certain that dressing changes do
not cause further damage. Tape should not be applied
directly to skin and bandages should be soaked off.
1351

Epidermolysis bullosa

pressure to the skin. Blistering often appears in
infancy in response to simply being held or handled.
In rarer forms of the disorder, EB can be life-threatening. There is no cure for the disorder. Treatment
focuses on preventing and treating wounds and
infection.

Epididymitis

Infection is a major concern, so a topical antibiotic,
such as bacitracin, mupirocin, or sulfadiazine, should
be routinely applied. Among persons with recessive
dystrophic EB, the anticonvulsant phenytoin is sometimes effective because it decreases production of an
enzyme that breaks down collagen.

Prognosis
The prognosis of EB varies depending on the
subtype of the disease. Individuals with EB simplex
can live long, fulfilling lives. The severity of the junctional and dystrophic forms of EB can vary greatly.
Infants affected with some forms of the disease often
do not survive infancy; other forms can lead to severe
scarring and disfigurement.
Resources
BOOKS

Fine, Jo-David, et al. Epidermolysis Bullosa:
Clinical,Epidemiologic, and Laboratory Advances, and
the Findings of the National Epidermolysis Bullosa
Registry. Baltimore: Johns Hopkins Univ Press,
1999.
Fitzpatrick, Thomas B., Richard A. Johnson, Wolff Klaus,
and Dick Suurmond. Color Atlas and Synopsis of
Clinical Dermatology. 4th ed. NewYork: McGraw-Hill,
2000.
Mallory, S.B. Atlas of Pediatric Dermatology. Pearl River,
NY: Parthenon, 2001.

Epididymitis
Definition
Epididymitis is inflammation or infection of the
epididymis. In this long coiled tube attached to the
upper part of each testicle, sperm mature and are
stored before ejaculation.

Description
Epididymitis is the most common cause of pain in
the scrotum. The acute form is usually associated with
the most severe pain and swelling. If symptoms last for
more than six weeks after treatment begins, the condition is considered chronic.
Epididymitis can occur any time after the onset of
puberty but is most common between the ages of 18
and 40. It is especially common among members of the
military who exercise for extended periods without
emptying their bladders.
Factors that increase the risk of developing epididymitis include:


infection of the bladder, kidney, prostate, or urinary
tract



other recent illness



narrowing of the urethra (the tube that drains urine
from the bladder)



use of a urethral catheter

PERIODICALS

Cotell, S., N. D. Robinson, and L. S. Chan.
‘‘AutoimmuneBlistering Skin Diseases.’’ American
Journal of Emerging Medicine 18, no. 3 (2000): 288–99.
ORGANIZATIONS

American Academy of Dermatology. PO Box 4014, 930 N.
Meacham Rd., Schaumburg, IL 60168-4014. (847) 3300230. Fax: (847) 330-0050. <http://www.aad.org>.
OTHER

Dermatology Online Atlas. <http://www.dermis.net/doia/
diagnose.asp?zugr=d&lang=e&diagnr=757320
&topic=t>.
Dystrophic Epidermolysis Bullosa Research Association
International. <http://debra-international.org/
index1.htm>.
Epidermolysis Bullosa Medical Research Foundation.
<http://www.med.stanford.edu/school/dermatology/
ebmrf/>.
Oregon Health Sciences University. <http://
www.ohsu.edu/cliniweb/C17/C17.800.865.410.html>.
University of Iowa College of Medicine. <http://
tray.dermatology.uiowa.edu/EBA-001.htm>.

L. Fleming Fallon, Jr., MD, PhD, DrPH
1352

Causes and symptoms
Although epididymitis can be caused by the same
organisms that cause some sexually transmitted
diseases (STDs) or occur after prostate surgery, the
condition is generally due to pus-generating bacteria
associated with infections in other parts of the body.
Epididymitis can also be caused by injury or infection of the scrotum or by irritation from urine that has
accumulated in the vas deferens (the duct through
which sperm travels after leaving the epididymis).
Epididymitis is characterized by sudden redness
and swelling of the scrotum. The affected testicle is
hard and sore, and the other testicle may feel tender.
The patient has chills and fever and usually has acute
urethritis (inflammation of the urethra).
Enlarged lymph nodes in the groin cause scrotal
pain that intensifies throughout the day and may
become so severe that walking normally becomes
impossible.
GALE ENCYCLOPEDIA OF MEDICINE

Laboratory tests used to diagnose epididymitis
include:


urinalysis and urine culture



examination of discharges from the urethra and
prostate gland



blood tests to measure white-cell counts

Treatment
Because epididymitis that affects both testicles
can make a man sterile, antibiotic therapy must be
initiated as soon as symptoms appear. To prevent
reinfection, medication must be taken exactly as prescribed, even if the patient’s symptoms disappear or he
begins to feel better. Over-the-counter anti-inflammatories can relieve pain but should not be used without
the approval of a family physician or urologist.
Bed rest is recommended until symptoms subside,
and patients are advised to wear athletic supporters
when they resume normal activities. If pain is severe, a
local anesthetic like lidocaine (Xylocaine) may be
injected directly into the spermatic cord.
Self-care
A patient who has epididymitis should not drink
beverages that contain caffeine. To prevent constipation, he should use stool softeners or eat plenty of fruit,
nuts, whole grain cereals, and other foods with laxative properties.
An ice bag wrapped in a towel can reduce pain and
swelling but should be removed from the inflamed
area for a few minutes every hour to prevent burns.
Strenuous activity should be avoided until symptoms disappear. Sexual activity should not be resumed
until a month after symptoms disappear.
If a second course of treatment doesn’t eradicate
stubborn symptoms, longterm anti-inflammatory
therapy may be recommended. In rare instances,
chronic symptoms require surgery.
Surgery
Each of the surgical procedures used to treat
epididymitis is performed under local anesthesia on
an outpatient basis. Both of them cause sterility.
Epididymectomy involves removing the inflamed
section of the epididymitis through a small incision in
the scrotum.
GALE ENCYCLOPEDIA OF MEDICINE

Bilateral vasectomy prevents fluid and sperm from
passing through the epididymis. This procedure is
usually performed on men who have chronic epididymitis or on elderly patients undergoing prostate
surgery.

Prognosis
Pain generally subsides 24–72 hours after treatment begins. Complete healing may take weeks or
months.

Prevention
Using condoms and not having sex with anyone
who has an STD can prevent some cases of
epididymitis.
Resources
OTHER

‘‘Epididymitis.’’ Digital Urology Journal. June 7, 1998.
<http://www.duj.com/epididymitis.html>.

Maureen Haggerty

Epidural abscess see Central nervous system
infections
Epidural anesthetic see Anesthesia, local

Epiglottitis
Definition
Epiglottitis is an infection of the epiglottis, which
can lead to severe airway obstruction.

Description
When air is inhaled (inspired), it passes through
the nose and the nasopharynx or through the mouth
and the oropharynx. These are both connected to the
larynx, a tube made of cartilage. The air continues
down the larynx to the trachea. The trachea then splits
into two branches, the left and right bronchi (bronchial tubes). These bronchi branch into smaller air
tubes that run within the lungs, leading to the small
air sacs of the lungs (alveoli).
Either food, liquid, or air may be taken in through
the mouth. While air goes into the larynx and the
respiratory system, food and liquid are directed into
the tube leading to the stomach, the esophagus.
1353

Epiglottitis

Diagnosis

Epiglottitis

Because food or liquid in the bronchial tubes or lungs
could cause a blockage or lead to an infection, the
airway is protected. The epiglottis is a leaf-like piece
of cartilage extending upwards from the larynx. The
epiglottis can close down over the larynx when someone is eating or drinking, preventing these food and
liquids from entering the airway.
Epiglottitis is an infection and inflammation of
the epiglottis. Because the epiglottis may swell considerably, there is a danger that the airway will be blocked
off by the very structure designed to protect it. Air is
then unable to reach the lungs. Without intervention,
epiglottitis has the potential to be fatal.
Epiglottitis is primarily a disease of two to sevenyear-old children, although older children and adults
can also contract it. Boys are twice as likely as girls to
develop this infection. Because epiglottitis involves
swelling and infection of tissues, which are all located
at or above the level of the epiglottis, it is sometimes
referred to as supraglottitis (supra, meaning above).
About 25% of all children with this infection also have
pneumonia.

Causes and symptoms
The most common cause of epiglottitis is infection
with the bacteria called Haemophilus influenzae type b.
Other types of bacteria are also occasionally responsible for this infection, including some types of
Streptococcus bacteria and the bacteria responsible
for causing diphtheria.
A patient with epiglottitis typically experiences a
sudden fever, and begins having severe throat and
neck pain. Because the swollen epiglottis interferes
significantly with air movement, every breath creates
a loud, harsh, high-pitched sound referred to as
stridor. Because the vocal cords are located in the
larynx just below the area of the epiglottis, the
swollen epiglottis makes the patient’s voice sound
muffled and strained. Swallowing becomes difficult,
and the patient may drool. The patient often leans
forward and juts out his or her jaw, while struggling
for breath.
Epiglottitis strikes suddenly and progresses
quickly. A child may begin complaining of a sore
throat, and within a few hours be suffering from extremely severe airway obstruction.

Diagnosis
Diagnosis begins with a high level of suspicion
that a quickly progressing illness with fever, sore
throat, and airway obstruction is very likely to be
1354

epiglottitis. If epiglottitis is suspected, no efforts
should be made to look at the throat, or to swab the
throat in order to obtain a culture for identification
of the causative organism. These maneuvers may
cause the larynx to go into spasm (laryngospasm),
completely closing the airway. These procedures
should only be performed in a fully-equipped operating room, so that if laryngospasm occurs, a breathing
tube can be immediately placed in order to keep the
airway open.
An instrument called a laryngoscope is often used
in the operating room to view the epiglottis, which will
appear cherry-red and quite swollen. An x-ray picture
taken from the side of the neck should also be
obtained. The swollen epiglottis has a characteristic
appearance, called the ‘‘thumb sign.’’

Treatment
Treatment almost always involves the immediate
establishment of an artificial airway: inserting a
breathing tube into the throat (intubation); or making
a tiny opening toward the base of the neck and putting
a breathing tube into the trachea (tracheostomy).
Because the patient’s apparent level of distress may
not match the actual severity of the situation, and
because the disease’s progression can be quite surprisingly rapid, it is preferable to go ahead and place the
artificial airway, rather than adopting a wait-and-see
approach.
Because epiglottitis is caused by a bacteria, antibiotics such as cefotaxime, ceftriaxone, or ampicillin
with sulbactam should be given through a needle
placed in a vein (intravenously). This prevents
the bacteria that are circulating throughout the bloodstream from causing infection elsewhere in the body.

Prognosis
With treatment (including the establishment of an
artificial airway), only about 1% of children with
epiglottitis die. Without the artificial airway, this figure jumps to 6%. Most patients recover form the
infection, and can have the breathing tube removed
(extubation) within a few days.

Prevention
Prevention involves the use of a vaccine against
H. influenzae type b (called the Hib vaccine). It is
given to babies at two, four, six, and 15 months.
Use of this vaccine has made epiglottitis a very rare
occurrence.
GALE ENCYCLOPEDIA OF MEDICINE

Epiglottis—A leaf-like piece of cartilage extending
upwards from the larynx, which can close like a lid
over the trachea to prevent the airway from receiving any food or liquid being swallowed.
Extubation—Removal of a breathing tube.
Intubation—Putting a breathing tube into the
airway.
Laryngospasm—Spasm of the larynx.
Larynx—The part of the airway lying between the
pharynx and the trachea.
Nasopharynx—The part of the airway into which
the nose leads.
Oropharynx—The part of the airway into which
the mouth leads.
Supraglottitis—Another term for epiglottitis.
Trachea—The part of the airway that leads into the
bronchial tubes.
Tracheostomy—A procedure in which a small
opening is made in the neck and into the trachea.
A breathing tube is then placed through this
opening.

Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.

Rosalyn Carson-DeWitt, MD

Epilepsy see Seizure disorder
Epinephrine see Bronchodilators

Episiotomy
Definition
An episiotomy is a surgical incision made in the
area between the vagina and anus (perineum). This is
done during the last stages of labor and delivery to
expand the opening of the vagina to prevent tearing
during the delivery of the baby.
GALE ENCYCLOPEDIA OF MEDICINE

This procedure is usually done during the delivery
or birthing process when the vaginal opening does not
stretch enough to allow the baby to be delivered without tearing the surrounding tissue.

Precautions
Prior to the onset of labor, pregnant women may
want to discuss the use of episiotomy with their care
providers. It is possible that, with adequate preparation and if the stages of labor and delivery are managed with adequate coaching and support, the need for
an episiotomy may be reduced.

Description
An episiotomy is a surgical incision, usually made
with sterile scissors, in the perineum as the baby’s head
is being delivered. This procedure may be used if the
tissue around the vaginal opening begins tearing or
does not seem to be stretching enough to allow the
baby to be delivered.
In most cases, the physician makes a midline incision along a straight line from the lowest edge of the
vaginal opening to toward the anus. In other cases, the
episiotomy is performed by making a diagonal incision across the midline between the vagina and anus.
This method is used much less often, may be more
painful, and may require more healing time than the
midline incision. After the baby is delivered through
the extended vaginal opening, the incision is closed
with stitches. A local anesthetic agent may be applied
or injected to numb the area before it is sewn up
(sutured).
Several reasons are cited for performing episiotomies. Some experts believe that an episiotomy
speeds up the birthing process, making it easier for
the baby to be delivered. This can be important if there
is any sign of distress that may harm the mother or
baby. Because tissues in this area may tear during the
delivery, another reason for performing an episiotomy
is that a clean incision is easier to repair than a jagged
tear and may heal faster. Although the use of episiotomy is sometimes described as protecting the pelvic
muscles and possibly preventing future problems with
urinary incontinence, it is not clear that the procedure
actually helps.
The use of episiotomy during the birthing process
is fairly widespread in the United States. Estimates of
episiotomy use in hospitals range from 65–95% of
deliveries, depending on how many times the mother
1355

Episiotomy

Purpose

KEY TERMS

Episiotomy

Injecting local anesthetic

Cutting the perineum

Closing the incision

An episiotomy is a surgical incision made in the perineum, the area of tissue between the vaginal opening and the anus, during
the birthing process. This procedure may be used if the tissue around the vaginal opening begins to tear or is not stretching
enough to allow the baby to be delivered vaginally. In the United States, the rate of episiotomies being performed is estimated at
65–95%. (Illustration by Electronic Illustrators Group.)

has given birth previously. This routine use of episiotomy is being reexamined in many hospitals and
health care settings. However, an episiotomy is always
necessary during a forceps delivery because of the size
of the forceps.

Preparation
It may be possible to avoid the need for an
episiotomy. Pregnant women may want to talk with
their care providers about the use of episiotomy
during the delivery. Kegel exercises are often recommended during the pregnancy to help strengthen the
pelvic floor muscles. Prenatal perineal massage may
help to stretch and relax the tissue around the vaginal
opening. During the delivery process, warm compresses can be applied to the area along with the use
of perineal massage. Coaching and support are also
important during the delivery process. A slowed,
controlled pushing during the second stage of labor
(when the mother gets the urge to push) may allow
the tissues to stretch rather than tear. Also, an upright
birthing position (rather than one where the mother is
lying down) may decrease the need for an episiotomy.

Aftercare
The area of the episiotomy may be uncomfortable
or even painful for several days. Several practices can
relieve some of the pain. Cold packs can be applied to
1356

the perineal area to reduce swelling and discomfort.
Use of the Sitz bath available at the hospital or birth
center can ease the discomfort, too. This unit circulates warm water over the area. A squirt bottle with
water can be used to clean the area after urination or
defecation rather than wiping with tissue. Also, the
area should be patted dry rather than wiped.
Cleansing pads soaked in witch hazel (such as Tucks)
are very effective for cleaning the area and also feel
soothing.

Risks
Several side effects of episiotomy have been
reported, including infection, increased pain, prolonged healing time, and increased discomfort once
sexual intercourse is resumed. There is also the risk
that the episiotomy incision will be deeper or longer
than is necessary to permit the birth of the infant.
There is a risk of increased bleeding.

Normal results
In a normal and well managed delivery, an episiotomy may be avoided altogether. If an episiotomy is
deemed to be necessary, a simple midline incision
will be made to extend the vaginal opening without
additional tearing or extensive trauma to the perineal
area. Although there may be some pain associated with
the healing of the episiotomy incision, relief can usually
GALE ENCYCLOPEDIA OF MEDICINE

Kegel exercises—A series of contractions and
relaxations of the muscles in the perineal area.
These exercises are thought to strengthen the pelvic
floor and may help prevent urinary incontinence in
women.
Perineum—The area between the opening of the
vagina and the anus in a woman, or the area
between the scrotum and the anus in a man.
Sitz bath—A shallow tub or bowl, sometimes
mounted above a toilet, that allows the perineum
and buttocks to be immersed in circulating water.
Urinary incontinence—The inability to prevent the
leakage or discharge of urine. This situation
becomes more common as people age, and is
more common in women who have given birth to
more than one child.

be provided with mild pain relievers and supportive
measures, such as the application of cold packs.

Abnormal results
An episiotomy incision that is too long or deep
may extend into the rectum, causing more bleeding
and an increased risk of infection. Additional tearing
or tissue damage may occur beyond the episiotomy
incision, leaving a cut and a tear to be repaired.
Resources
OTHER

Childbirth.org. <http://www.childbirth.org>.

Altha Roberts Edgren

Epispadias see Hypospadias and epispadias
Epistaxis see Nosebleed
EPS see Electrophysiology study of the heart

Epstein-Barr virus test
Definition
The Epstein-Barr virus test is a blood test, or
group of tests, to determine the presence or absence
of antibodies in the blood stream directed against
GALE ENCYCLOPEDIA OF MEDICINE

proteins of the Epstein-Barr virus, the cause of
infectious mononucleosis.

Purpose
The test is primarily used to detect whether first
time infection (called primary infection) with the
Epstein-Barr virus is currently occurring, or has
occurred within a short period of time. The pattern
of the antibodies detected can, however, tell if the
person has never been infected with the Epstein-Barr
virus, or if the infection occurred in the more distant
past. These tests are mostly utilized in the diagnosis of
Epstein-Barr virus-associated infectious mononucleosis when the more common diagnostic test, the heterophile antibody, is negative, or in situations where the
infection is manifesting unusual symptoms. Therefore,
the tests are often not needed in a situation where a
doctor believes that a person has mononucleosis and
the heterophile test (also called the monospot test) is
positive.
In addition, Epstein-Barr virus testing is usually
not needed in the evaluation of a patient who has
long-lasting fatigue, and may have the chronic fatigue
syndrome. Initially, it was thought that discovering a
particular pattern of antibodies to this virus was
helpful in the diagnosis of chronic fatigue syndrome,
but this no longer appears to be the case.

Precautions
As in any blood test, standard precautions should
be performed to prevent infection at the site where the
blood is obtained, and to prevent excess bleeding.
Normally, the site is cleaned with an antiseptic
liquid prior to the blood being obtained; a sterile
non-reusable needle and syringe are used; and, once
the needle is removed, pressure is placed at the site
until bleeding has stopped.

Description
These tests are more often performed in a consulting laboratory than at a physician’s office or in a
hospital laboratory. Like most antibody tests, they
are performed on serum, the liquid part of the blood
obtained after the whole blood is allowed to clot in
a tube. Antibodies can be detected against several
components of the Epstein-Barr virus (EBV). These
components are the EBV early antigen (EA), the viral
capsid antigen (VCA), and the nuclear antigen
(EBNA). These several antigens are different proteins
that are produced in the process (stages) of the virus’
growth.
1357

Epstein-Barr virus test

KEY TERMS

Epstein-Barr virus test

At the time of infection with Epstein-Barr virus,
antibodies to EA are found and usually last for four to
six months only. This antibody, however, persists
substantially longer in about 10% of persons who
have had EBV infection in the more remote past. The
absence of antibody to EA when other EBV antibodies
are present strongly suggests that first time infection
with EBV occurred in the past.
Antibody to VCA is found both early and late in
EBV infection. At the time of infection, antibody of
both the IgM and IgG types are detectable. After four
to six months, usually, only the IgG antibody against
VCA can be found.
Unlike antibodies to EA and VCA, antibody to
EBNA does not usually develop until recovery from
first time infection of this virus. Therefore, finding
detectable amounts of antibody to EBNA during an
illness which might be caused by EBV makes the
causal relationship very unlikely.

Preparation
The skin area from which the blood sample will be
obtained is wiped with an antiseptic such as alcohol or
iodine.

or having had it in the past, and call that category
two. Most young children below the age of five will
fall into category one, while most adults over the age
of 20 years will fall into category two.
The results for susceptibility are:


antibody to EA = negative



antibody to VCA (either IgM or IgG) = negative



antibody to EBNA = negative
The results for past infection are:



antibody to EA = negative (90% of time)



antibody to VCA IgM = negative



Antibody to VCA IgG = positive



Antibody to EBNA = Positive.

It is important to realize that the Epstein-Barr
virus, like all the human herpes viruses, does not
totally leave the body after the patient recovers from
illness. With EBV, the virus will intermittently recur in
the saliva of people without any symptoms. Such people will have a test pattern of previous infection. It is
this group of people who can transmit EBV to others
without themselves being ill.

Abnormal results

Aftercare
The aftercare is similar to that for any blood test.
Usually, pressure is applied to the area for several
moments until bleeding stops. If the results are difficult
to interpret, it may be necessary to re-test later, after
waiting one to three weeks. The change in the amounts
of antibody detected between the two tests can be particularly useful, at times, in helping to make a diagnosis.

Risks
There are no risks over and above those of having
blood drawn for any other purpose. These tests are
more expensive than many other blood tests but are
usually covered by medical insurance.

Normal results
The pattern of the three antibodies can be used to
determine whether the person has not had infection
with EBV to this point (is susceptible to infection); is
currently, or recently, infected with EBV for the
first time; or has had first time infection with EBV
sometime in the past (more than six months ago).
If one defines ‘‘normal’’ results as either not
having EBV in the past, and call that category one;
1358

The results for current or recent infection are:


antibody to EA = positive



antibody to VCA IgM = positive



antibody to VCA IgG = positive



antibody to EBNA = negative.

Without the pattern of the three antibodies, it can
be difficult to be accurate in interpretation. The presence of antibody to VCA IgM is the best single test
for current or recent first time infection.
Resources
PERIODICALS

Henle, G., W. Henle, and C. A. Horowitz. ‘‘Epstein-Barr
Virus Specific Diagnosis: Tests in Infectious
Mononucleosis.’’ Human Pathology 5 (1997): 551-558.

Larry I. Lutwick, MD, FACP

ERCP see Endoscopic retrograde
cholangiopancreatography
Erectile disorder see Impotence
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Erectile dysfunction (ED), formerly known as
impotence, is the inability to achieve or maintain an
erection long enough to engage in sexual intercourse.

Description
Under normal circumstances, when a man is
sexually stimulated, his brain sends a message down
the spinal cord and into the nerves of the penis. The
nerve endings in the penis release chemical messengers,
called neurotransmitters, that signal the arteries that
supply blood to the corpora cavernosa (the two
spongy rods of tissue that span the length of the
penis) to relax and fill with blood. As they expand,
the corpora cavernosa close off other veins that
would normally drain blood from the penis. As the
penis becomes engorged with blood, it enlarges and
stiffens, causing an erection. Problems with blood
vessels, nerves, or tissues of the penis can interfere
with an erection.

Causes and symptoms
It is estimated that up to 30 million American
men frequently suffer from ED and that it strikes up
to half of all men between the ages of 40 and 70.
Doctors used to think that most cases of ED were
psychological in origin, but they now recognize that,
at least in older men, physical causes may play a
primary role in 60% or more of all cases. In men
over the age of 60, the leading cause is atherosclerosis,
or narrowing of the arteries, which can restrict the
flow of blood to the penis. Injury or disease of the
connective tissue, such as Peyronie’s disease, may
prevent the corpora cavernosa from completely
expanding. Damage to the nerves of the penis from
certain types of surgery or neurological conditions,
such as Parkinson’s disease or multiple sclerosis, may
also cause ED. Men with diabetes are especially at
risk for erectile dysfunction because of their high risk
of both atherosclerosis and a nerve disease called
diabetic neuropathy.
Some drugs, including certain types of blood
pressure medications, antihistamines, tranquilizers
(especially before intercourse), and antidepressants
known as selective serotonin reuptake inhibitors
(SSRIs, including Prozac and Paxil) can interfere
with erections. Smoking, excessive alcohol consumption, and illicit drug use may also contribute. In some
cases, low levels of the male hormone testosterone may
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
When diagnosing the underlying cause of erectile
dysfunction, the doctor begins by asking the man a
number of questions about when the problem began,
whether it only happens with specific sex partners, and
whether he ever wakes up with an erection. (Men
whose dysfunction occurs only with certain partners
or who wake up with erections are more likely to have
a psychological cause for their ED.) Sometimes, the
man’s sex partner is also interviewed. In some cases,
domestic discord may be a factor.
The doctor also obtains a thorough medical
history to find out about past pelvic surgery, diabetes,
cardiovascular disease, kidney disease, and any
medications the man may be taking. The physical
examination should include a genital examination,
hormone tests, and a glucose test for diabetes.
Sometimes a measurement of blood flow through the
penis may be taken.

Treatment
Years ago, the standard treatment for erectile
dysfunction was a penile implant or long-term psychotherapy. Although physical causes are now more
readily diagnosed and treated, individual or marital
counseling is still an effective treatment for ED when
emotional factors play a role.
There are three prescription medications available in the United States to treat the physical causes
of ED: sildenafil citrate (Viagra), vardenafil
(Levitra), and tadalafil (Cialis). They help about
three-fourths of all men who try them in the general
population. Several studies have indicated that their
success rate in diabetic men may be slightly lower,
averaging around 60–65%. All three pills work by
enhancing the effects of nitric oxide. This chemical
relaxes muscles in the penis to allow more blood
to flow in. These pills do not cause an erection by
themselves. Sexual stimulation is also required.
Sildenafil or vardenafil should be taken about an
hour before sex. Each is effective for roughly four
hours. Tadalafil lasts for up to 36 hours. Men should
not have sex more than once every 24 hours after
using these drugs. Before Viagra’s approval in 1998,
drug treatment of erectile dysfunction was limited to
alprostadil (prostaglandin [E.sub.1]), either injected
1359

Erectile dysfunction

Erectile dysfunction

contribute to erectile failure. Finally, psychological
factors, such as stress, guilt, or anxiety, may also
play a role, even when the ED is primarily due to
organic causes.

Erectile dysfunction

into the penis or inserted as a pellet into the
urethra. Sales of the three newer ED drugs reached
$3.4 billion in 2004, according to the research firm
IMS Health. In 2004, Viagra had about 66% of the
market share for ED drugs compared to 19% for
Levitra and 14% for Cialis.
Viagra
Sildenafil citrate was originally developed in
1991 as a treatment for angina, or chest pain. The
drug, marketed under the name Viagra, received
FDA approval as a treatment for erectile dysfunction in March 1998, and since that time it has been
prescribed for more then 20 million men worldwide.
It was the first oral medication approved for
ED treatment. Viagra is a vasodilator, a drug that
has the effect of dilating the blood vessels. It works
by improving blood circulation to the penis, and
by enhancing the effects of nitric oxide, the agent
that relaxes the smooth muscle of the penis and
regulates blood vessels during sexual stimulation,
allowing the penis to become engorged and achieve
an erection.
The average recommended dose of Viagra is 50
mg. It comes in doses of 25 mg., 50 mg., and 100 mg to.
The medication is taken approximately one hour
before sexual activity is planned, and may remain
effective for up to four hours. One drawback is that
to be effective, it should be taken on an empty
stomach. Also, high-fat foods can interfere with the
absorption of Viagra. Viagra does not increase sexual
desire. Sexual stimulation and arousal are required for
it to be effective.
Many insurance plans cover the cost of Viagra,
provided it is prescribed to treat erectile dysfunction.
The pills cost approximately $10 each, and insurers
may limit coverage to a specific number of pills each
month.
The primary drawback to Viagra, which works
about an hour after it is taken, it that the FDA
cautions men with heart disease or low blood pressure
to be thoroughly examined by a physician before
obtaining a prescription. At least 130 men have died
while taking Viagra. However, the FDA said the
men—most over the age of 64—died of heart attack
or stroke due to health problems exaggerated by
sexual activity, not the drug itself.
Levitra
In early 2003, a second prescription drug to treat
erectile dysfunction, Levitra, was approved by the
FDA. Like Viagra, Levitra helps increase blood flow
1360

to the penis and may help men with ED get and keep
an erection. Once a man has completed sexual activity,
blood flow to the penis should decrease and the
erection should go away. Levitra should be taken
approximately 60 minutes prior to sexual activity. In
clinical trials, most patients were able to begin sexual
activity before that time. A 2004 study showed that
about 50% of men taking Levitra experienced a firm
erection within 25 minutes and a small percentage in as
quickly as 10 minutes. Studies also showed that
Levitra improved erectile function in men who had
other health factors, such as diabetes or prostate
surgery.
Men taking nitrate drugs, often used to control
chest pain (also known as angina), should not take
Levitra. Men who use alpha-blockers, sometimes prescribed for high blood pressure or prostate problems,
also should not take Levitra. Such combinations could
cause blood pressure to drop to an unsafe level.
Levitra is available in 2.5 mg, 5 mg, 10 mg, and 20
mg tablets and should be taken no more than once a
day. The average cost per pill is about $10 and is
covered by many insurance plans.
Cialis
Cialis is the third oral drug prescribed to treat
erectile dysfunction, approved by the FDA in
November 2003. Its most notable difference from
Viagra and Levitra, which work for about four
hours, is that Cialis works for up to 36 hours. Cialis
helps increase blood flow in the penis when a man is
sexually stimulated. It can help men with ED get and
keep an erection satisfactory for sexual activity. Once
a man has completed sexual activity, blood flow to his
penis decreases, and his erection goes away. Cialis is
clinically proven to improve erectile function in most
men with ED, including those with mild, moderate or
severe ED.
The most common side effects with Cialis are
headache, upset stomach, back pain, and muscle
aches. These side effects usually go away after a few
hours. Patients who get back pain and muscle aches
usually get it 12 to 24 hours after taking Cialis. Back
pain and muscle aches usually go away by themselves
within 48 hours.
Cialis comes in 5 mg., 10 mg. (the recommended
starting dose), and 20 mg. tablets. The average cost
per tablet is about $10 and it is covered by many
insurance plans. Since the absorption of Cialis is
not affected by food or high-fat foods, it does not
need to be taken on an empty stomach. Studies
GALE ENCYCLOPEDIA OF MEDICINE

Priapism, a prolonged erection, is a very rare
potential side effect of all prescription ED medications. Persons taking Viagra, Levitra, or Cialis who
have a prolonged erection, lasting more than four
hours, should seek immediate medical attention.
Priapism can cause damage to the penis potentially
leading to the permanent inability to have an erection.
Because sexual activity can stress the heart, men
who have heart problems should check with their
physician to see if sexual activity is recommended.
Erectile dysfunction drugs may trigger temporary
hypotension (low blood pressure) and is known to
increase cardiovascular nerve activity, so physicians
should prescribe them with caution in men with a
history of heart attack, atherosclerosis (hardening of
the arteries), angina, arrhythmia, and chronic low
blood pressure problems. ED drugs are not labeled
or approved for use by women or children, or by
men without erectile dysfunction. Anyone experiencing cardiovascular symptoms such as dizziness,
chest or arm pain, and nausea when participating in
sexual activity after taking an ED medication should
stop the encounter. They should also not take any
ED drug again until they have discussed the episode
with their healthcare provider. It is recommended
that men with kidney or liver impairments, and men
over age 65, start at the lowest possible dosage of ED
medications.
Other treatment options
Although the commercial availability of Viagra,
Levitra, and Cialis has been useful in many men, prostate cancer patients and ED caused by psychological
problems often require alternative treatment. A commonly used alternative consists of a three-drug injection containing alprostadil, papaverine hydrochloride,
and phentolamine mesylate. Though it is commonly
referred to as the ‘‘Knoxville formula,’’ apparently for
the city of its original introduction, a number of
slightly varying formulas have been in use around
the country. The three-drug preparation is administered by injection into the corpora cavernosa to induce
erection.
Other traditional therapies for ED include
vacuum pump therapy, injection therapy involving
injecting a substance into the penis to enhance blood
flow, and a penile implantation device. In rare cases, if
narrowed or diseased veins are responsible for ED,
GALE ENCYCLOPEDIA OF MEDICINE

surgeons may reroute the blood flow into the corpora
cavernosa or remove leaking vessels.
In vacuum pump therapy, a man inserts his penis
into a clear plastic cylinder and uses a pump to force
air out of the cylinder. This forms a partial vacuum
around the penis, which helps to draw blood into
the corpora cavernosa. The man then places a special
ring over the base of the penis to trap the blood
inside it. The only side effect with this type of treatment is occasional bruising if the vacuum is left on
too long.
Injection therapy involves injecting a substance
into the penis to enhance blood flow and cause an
erection. The FDA approved a drug called alprostadil
(Caverject) for this purpose in 1995. Alprostadil
relaxes smooth muscle tissue to enhance blood flow
into the penis. It must be injected shortly before intercourse. Another, similar drug that is sometimes used is
papaverine. Either drug may sometimes cause painful
erections or priapism that must be treated with a shot
of epinephrine. Alprostadil may also be administered
into the urethral opening of the penis. In MUSE
(medical urethral system for erection), the man inserts
a thin tube the width of a spaghetti noodle into his
urethral opening and presses down on a plunger to
deliver a tiny pellet containing alprostadil into his
penis. The drug takes about 10 minutes to work and
the erection lasts about an hour. The main side effect is
a sensation of pain and burning in the urethra, which
can last about five to 15 minutes. The injection process
itself is often painful
Implantable penile prostheses are usually considered a last resort for treating erectile dysfunction.
They are implanted in the corpora cavernosa to
make the penis rigid without the need for blood flow.
The semi-rigid type of prosthesis consists of a pair of
flexible silicone rods that can be bent up or down. This
type of device has a low failure rate but, unfortunately,
it causes the penis to always be erect, which can be
difficult to conceal under clothing.
The inflatable type of device consists of cylinders
that are implanted in the corpora cavernosa, a fluid
reservoir implanted in the abdomen, and a pump
placed in the scrotum. The man squeezes the pump
to move fluid into the cylinders and cause them to
become rigid. (He reverses the process by squeezing
the pump again.) While these devices allow for intermittent erections, they have a slightly higher malfunction rate than the silicon rods. Men can return to
sexual activity six to eight weeks after implantation
surgery. Since implants affect the corpora cavernosa,
1361

Erectile dysfunction

show that in most men, Cialis begins working in
about 30 minutes and may be taken up to once per
day by most patients.

Erectile dysfunction

they permanently take away a man’s ability to have a
natural erection.

Alternative treatment
A number of herbs have been promoted for
treating erectile dysfunction. The most widely touted
is yohimbe (Corynanthe yohimbe), derived from
the bark of the yohimbe tree native to West Africa.
It has been used in Europe for about 75 years to treat
ED. The FDA approved yohimbe as a treatment
for ED in the late 1980s. It is sold as an over-thecounter dietary supplement and as a prescription
drug under brand names such as Yocon,
Aphrodyne, Erex, Yohimex, Testomar, Yohimbe,
and Yovital.
There is no clear medical research that indicates
exactly how or why yohimbe works in treating ED. It
is generally believed that yohimbe dilates blood vessels and stimulates blood flow to the penis, causing an
erection. It also prevents blood from flowing out of
the penis during an erection. It may also act on the
central nervous system, specifically the lower spinal
cord area where sexual signals are transmitted.
Studies show it is effective to some degree in 30–
40% of men with ED. It is primarily effective in
men with ED caused by vascular, psychogenic (originating in the mind), or diabetic problems. It usually
does not work in men whose dysfunction is caused by
organic nerve damage. In healthy men without ED,
yohimbe in some cases appears to increase sexual
stamina and prolong erections. The usual dosage of
yohimbine (yohimbe extract) to treat ED is 5.4 mg
three times a day. It may take three to six weeks for it
to take effect.
Ginkgo Ginkgo biloba, is also used to treat erectile
dysfunction, although it has not been shown to help
the condition in controlled studies, and probably has
more of a psychological effect. In addition, ginkgo
carries some risk of abnormal blood clotting and
should be avoided by men taking blood thinners,
such as coumadin. Other herbs promoted for treating
ED include true unicorn root Aletrius farinosa, saw
palmettoSerenoa repens, ginseng Panax ginseng, and
Siberian ginseng Eleuthrococcus senticosus. Nux
vomica Strychnos nux-vomica has been recommended,
especially when ED is caused by excessive alcohol,
cigarettes, or dietary indiscretions. Nux vomica can
be very toxic if taken improperly, so it should be used
only under the strict supervision of a physician trained
in its use.
There are quite a few Chinese herbal remedies
for erectile dysfunction usually combinations of
1362

KEY TERMS
Angina—A condition in which lack of blood to the
heart causes severe chest pain.
Antihistamines—A drug that blocks cell receptors
for histamine, usually to prevent allergic effects
such as sneezing and itching.
Arrhythmia—An irregularity in the normal rhythm
or force of the heartbeat.
Atherosclerosis—An arterial disease in which
raised areas of degeneration and cholesterol deposits (plaques) form on the inner surfaces of the
arteries. Also called hardening of the arteries.
Corpora cavernosa—Either of a pair of columns of
erectile tissue at either side of the penis that,
together with the corpus spongiosum, produce an
erection when filled with blood.
Diabetic neuropathy—A disease or disorder, especially a degenerative one, caused by diabetes that
affects the nervous system.
Neurotransmitter—A chemical that carries messages between different nerve cells or between
nerve cells and muscles.
Peyronie’s disease—Local fibrous scarring causing
the erect penis to be bent to such a degree that it
interferes with sexual intercourse.
Priapism —A prolonged erection lasting more than
four hours.
SSRIs—Selective serotonin reuptake inhibitors, a
class of medication used to treat depression.
Vasodilator—An agent, such as a nerve or hormone,
that widens the blood vessels, which in turn
decreases resistance to blood flow and lowers
blood pressure.

herbs and sometimes animal parts such as deer
antler and sea horse. Acupuncture is also used to
treat ED, although Western doctors question its
effectiveness.

Prognosis
With proper diagnosis, erectile dysfunction
can nearly always be treated or coped with successfully. Unfortunately, fewer than 10% of men with
ED seek treatment. However, with the heavy advertising and marketing associated with Viagra,
GALE ENCYCLOPEDIA OF MEDICINE

Prevention

OTHER

December 2003. National Kidney and Urologic Diseases
Information ClearinghouseErectile Dysfunction http://
kidney.niddk.nih.gov/kudiseases/pubs/impotence/
(Accessed March 24, 2005).

There is no specific treatment to prevent erectile
dysfunction. Perhaps the most important measure is
to maintain general good health and avoid atherosclerosis by exercising regularly, controlling weight,
controlling hypertension and high cholesterol levels,
and not smoking. Avoiding excessive alcohol intake
may also help.
Resources
BOOKS

Ken R. Wells

Erectile dysfunction treatment
Definition

Icon Health Publications.The Official Patient’s Sourcebook
on Erectile Dysfunction: A Revised and Updated
Directory for the Internet Age. San Diego: Icon Health
Publications, 2005.
Kloner, Robert A. Heart Disease and Erectile Dysfunction.
Totowa, NJ: Humana Press, 2004.
Lue, Tom F. An Atlas of Erectile Dysfunction, Second
Edition. London: Taylor & Francis Group, 2003.
Metz, Michael E. and Barry W. McCarthy.Coping With
Erectile Dysfunction: How to Regain Confidence and
Enjoy Great Sex Oakland, CA: New Harbinger
Publications, 2004.

Drugs and devices that treat erectile dysfunction
(ED), the inability to achieve or maintain an erection
long enough to engage in sexual intercourse.

PERIODICALS

Because sexual activity can stress the heart, men
who have heart problems should check with their
physician to see if sexual activity is recommended.
Erectile dysfunction drugs may trigger temporary hypotension (low blood pressure) and is known to increase
cardiovascular nerve activity, so physicians should prescribe them with caution in men with a history of heart
attack, atherosclerosis (hardening of the arteries),
angina, arrhythmia, and chronic low blood pressure
problems. ED drugs are not labeled or approved for
use by women or children, or by men without erectile
dysfunction. Anyone experiencing cardiovascular
symptoms such as dizziness, chest or arm pain, and
nausea when participating in sexual activity after
taking an ED medication should stop the encounter.
They should also not take any ED drug again until
they have discussed the episode with their healthcare
provider. It is recommended that men with kidney or
liver impairments, and men over age 65, start at the
lowest possible dosage of ED medications.

Roberts, Shauna S. ‘‘Options Increase for Men
With Erectile Dysfunction: Doctors Now
Have an Array of Treatments for Men’s Sexual
Problems.’’ Diabetes Forecast (September 2004):
55-58.
Sadovsky, Richard. ‘‘Sildenafil is Safe and Effective in Men
With Stable CAD.’’American Family Physician
(September 1, 2004): 955.
Tomlinson, John. ‘‘The Patient With Erectile Dysfunction.’’
The Practitioner (February 9,
2005): 104.
Trissel, Lawrence A. ‘‘Long-Term Stability of Trimix: A
Three-Drug Injection Used to Treat Erectile
Dysfunction.’’ International Journal of Pharmaceutical
Compounding (May-June 2004): 231-235.
Wooten, James M. ‘‘Erectile Dysfunction: There are Now
Three Effective Oral Drugs for Treating ED, Paving
the Way for Nurses to Put Patients With This
Condition on the Road to Good Sexual Health.’’ RN
(October 2004): 40.
Zoler, Mitchel L. ‘‘Drug Update: Erectile Dysfunction.’’
OB/GYN News (April 15, 2004): 92.
ORGANIZATIONS

Erectile Dysfunction Information Center. 10949 Bren Road
East, Minnetonka, MN 55343-9613. (866) 294-7508.
publisher@erectile-dysfunction-impotence.org. http://
www.cure-ed.org. 952-852-5560
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
The purpose of ED treatment is to allow men to
achieve and maintain an erection of sufficient strength
and duration to engage in sexual intercourse.

Precautions

Description
There are three prescription medications available
in the United States to treat the physical causes of ED:
sildenafil citrate (Viagra), vardenafil (Levitra), and
tadalafil (Cialis). They help about three-fourths of all
1363

Erectile dysfunction treatment

Levitra, and Cialis, this number is expected to rise
dramatically.

Erectile dysfunction treatment

men who try them in the general population. Several
studies have indicated that their success rate in diabetic
men may be slightly lower, averaging around 60-65%.
All three pills work by enhancing the effects of nitric
oxide. This chemical relaxes muscles in the penis to
allow more blood to flow in. These pills do not cause
an erection by themselves. Sexual stimulation is also
required. Sildenafil or vardenafil should be taken about
an hour before sex. Each is effective for roughly four
hours. Tadalafil lasts for up to 36 hours. Men should
not have sex more than once every 24 hours after using
these drugs. Before Viagra’s approval in 1998, drug
treatment of erectile dysfunction was limited to alprostadil (prostaglandin), either injected into the penis or
inserted as a pellet into the urethra. Sales of the three
newer ED drugs reached $3.4 billion in 2004, according
to the research firm IMS Health. In 2004, Viagra had
about 66% of the market share for ED drugs compared
to 19% for Levitra and 14% for Cialis.

blood flow to the penis should decrease and the
erection should go away. Levitra should be taken
approximately 60 minutes prior to sexual activity. In
clinical trials, most patients were able to begin sexual
activity before that time. A 2004 study showed that
about 50% of men taking Levitra experienced a firm
erection within 25 minutes and a small percentage in as
quickly as 10 minutes. Studies also showed that Levitra
improved erectile function in men who had other health
factors, such as diabetes or prostate surgery.
Men taking nitrate drugs, often used to control
chest pain (also known as angina), should not take
Levitra. Men who use alpha-blockers, sometimes
prescribed for high blood pressure or prostate
problems, also should not take Levitra. Such combinations could cause blood pressure to drop to an
unsafe level. Levitra is available in 2.5 mg, 5 mg, 10
mg, and 20 mg tablets.
Cialis

Viagra
Sildenafil was originally developed in 1991 as a
treatment for angina, or chest pain. The drug, marketed under the name Viagra, received FDA approval
as a treatment for erectile dysfunction in March 1998,
and since that time it has been prescribed for more
then 20 million men worldwide. It was the first oral
medication approved for ED treatment. Viagra is a
vasodilator, a drug that has the effect of dilating the
blood vessels. It works by improving blood circulation
to the penis, and by enhancing the effects of nitric
oxide, the agent that relaxes the smooth muscle of
the penis and regulates blood vessels during sexual
stimulation, allowing the penis to become engorged
and achieve an erection.
The average recommended dose of Viagra is 50
mg. It comes in doses of 25 mg., 50 mg., and 100 mg to.
The medication is taken approximately one hour
before sexual activity is planned, and may remain
effective for up to four hours. One drawback is
that to be effective, it should be taken on an empty
stomach. Also, high-fat foods can interfere with the
absorption of Viagra. Viagra does not increase sexual
desire. Sexual stimulation and arousal are required
for it to be effective.
Levitra
In early 2003, a second prescription drug to treat
erectile dysfunction, Levitra, was approved by the
FDA. Like Viagra, Levitra helps increase blood flow
to the penis and may help men with ED get and keep an
erection. Once a man has completed sexual activity,
1364

Cialis is the third oral drug prescribed to treat
erectile dysfunction, approved by the FDA in
November 2003. Its most notable difference from
Viagra and Levitra, which work for about four hours,
is that Cialis works for up to 36 hours. Cialis helps
increase blood flow in the penis when a man is sexually
stimulated. It can help men with ED get and keep an
erection satisfactory for sexual activity. Once a man has
completed sexual activity, blood flow to his penis
decreases, and his erection goes away. Cialis is clinically
proven to improve erectile function in most men with
ED, including those with mild, moderate or severe ED.
The most common side effects with Cialis are
headache, upset stomach, back pain, and muscle
aches. These side effects usually go away after a few
hours. Patients who get back pain and muscle aches
usually get it 12 to 24 hours after taking Cialis. Back
pain and muscle aches usually go away by themselves
within 48 hours.
Cialis comes in 5 mg., 10 mg. (the recommended
starting dose), and 20 mg. tablets. Since the absorption
of Cialis is not affected by food or high-fat foods, it
does not need to be taken on an empty stomach.
Studies show that in most men, Cialis begins working
in about 30 minutes and may be taken up to once per
day by most patients.
The cost of Viagra, Levitra, and Cialis is about
$10 per dose and is covered by most insurance plans.
Although the commercial availability of Viagra,
Levitra, and Cialis has been useful in many men,
prostate cancer patients and ED caused by psychological problems often require alternative treatment. A
GALE ENCYCLOPEDIA OF MEDICINE

Other traditional therapies for ED include
vacuum pump therapy, injection therapy involving
injecting a substance into the penis to enhance blood
flow, and a penile implantation device. In rare cases, if
narrowed or diseased veins are responsible for ED,
surgeons may reroute the blood flow into the corpora
cavernosa or remove leaking vessels.
In vacuum pump therapy, a man inserts his
penis into a clear plastic cylinder and uses a pump
to force air out of the cylinder. This forms a partial
vacuum around the penis, which helps to draw blood
into the corpora cavernosa. The man then places a
special ring over the base of the penis to trap the
blood inside it. The only side effect with this type of
treatment is occasional bruising if the vacuum is left
on too long.
Injection therapy involves injecting a substance
into the penis to enhance blood flow and cause an
erection. The FDA approved a drug called alprostadil
(Caverject) for this purpose in 1995. Alprostadil
relaxes smooth muscle tissue to enhance blood flow
into the penis. It must be injected shortly before intercourse. Another, similar drug that is sometimes used is
papaverine. Either drug may sometimes cause painful
erections or priapism that must be treated with a shot
of epinephrine. Alprostadil may also be administered
into the urethral opening of the penis. In MUSE
(medical urethral system for erection), the man inserts
a thin tube the width of a spaghetti noodle into his
urethral opening and presses down on a plunger to
deliver a tiny pellet containing alprostadil into his
penis. The drug takes about 10 minutes to work and
the erection lasts about an hour. The main side effect is
a sensation of pain and burning in the urethra, which
can last about five to 15 minutes. The injection process
itself is often painful
Implantable penile prostheses are usually considered a last resort for treating erectile dysfunction.
They are implanted in the corpora cavernosa to
make the penis rigid without the need for blood
flow. The semi-rigid type of prosthesis consists of a
pair of flexible silicone rods that can be bent up or
down. This type of device has a low failure rate
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Angina—A condition in which lack of blood to the
heart causes severe chest pain.
Arrhythmia—An irregularity in the normal rhythm
or force of the heartbeat.
Atherosclerosis—An arterial disease in which
raised areas of degeneration and cholesterol deposits (plaques) form on the inner surfaces of the
arteries. Also called hardening of the arteries.
Corpora cavernosa—Either of a pair of columns of
erectile tissue at either side of the penis that,
together with the corpus spongiosum, produce an
erection when filled with blood.
Priapism —A prolonged erection lasting more than
four hours.
Vasodilator—An agent, such as a nerve or hormone, that widens the blood vessels, which in
turn decreases resistance to blood flow and lowers
blood pressure.

but, unfortunately, it causes the penis to always be
erect, which can be difficult to conceal under clothing.
The inflatable type of device consists of cylinders
that are implanted in the corpora cavernosa, a fluid
reservoir implanted in the abdomen, and a pump placed
in the scrotum. The man squeezes the pump to move
fluid into the cylinders and cause them to become rigid.
(He reverses the process by squeezing the pump again.)
While these devices allow for intermittent erections,
they have a slightly higher malfunction rate than the
silicon rods. Men can return to sexual activity six to
eight weeks after implantation surgery. Since implants
affect the corpora cavernosa, they permanently take
away a man’s ability to have a natural erection.

Preparation
No preparation is needed for Viagra, Levitra, or
Cialis.

Aftercare
The primary aftercare is to monitor blood pressure following use of ED medications.

Risks
Priapism, a prolonged erection, is a very rare
potential side effect of all prescription ED
1365

Erectile dysfunction treatment

commonly used alternative consists of a three-drug
injection containing alprostadil, papaverine hydrochloride, and phentolamine mesylate. Though it is
commonly referred to as the ‘‘Knoxville formula,’’
apparently for the city of its original introduction, a
number of slightly varying formulas have been in use
around the country. The three-drug preparation is
administered by injection into the corpora cavernosa
to induce erection.

Erysipelas

medications. Persons taking any erectile dysfunction
medication who have a prolonged erection, lasting
more than four hours, should seek immediate
medical attention. Priapism can cause damage to the
penis potentially leading to the permanent inability to
have an erection.

Normal results
The goal of all ED treatments is to achieve and
maintain an erection strong enough to engage in
sexual intercourse, which is usually 30-60 minutes.

Zoler, Mitchel L. ‘‘Drug Update: Erectile Dysfunction.’’
OB/GYN News (April 15, 2004): 92.
ORGANIZATIONS

Erectile Dysfunction Information Center. 10949 Bren Road
East, Minnetonka, MN 55343-9613. (866) 294-7508.
publisher@erectile-dysfunction-impotence.org. http://
www.cure-ed.org. 952-852-5560
OTHER

National Kidney and Urologic Diseases Information
Clearinghouse Erectile Dysfunction. December 2003.
http://kidney.niddk.nih.gov/kudiseases/pubs/
impotence/ (cited March 31, 2005).

Ken R. Wells

Abnormal results
The most common abnormal response is the failure
to achieve and maintain and erection strong enough
and long enough to engage in sexual intercourse.

Ergotamine see Antimigraine drugs
Erosive gastritis see Gastritis

Resources
BOOKS

Icon Health Publications. The Official Patient’s Sourcebook
on Erectile Dysfunction: A Revised and Updated
Directory for the Internet Age. San Diego: Icon Health
Publications, 2005.
Kloner, Robert A.Heart Disease and Erectile Dysfunction.
Totowa, NJ: Humana Press, 2004.
Lue, Tom F. An Atlas of Erectile Dysfunction, Second
Edition. London: Taylor & Francis Group, 2003.
Metz, Michael E. and Barry W. McCarthy. Coping With
Erectile Dysfunction: How to Regain Confidence and
Enjoy Great Sex. Oakland, CA: New Harbinger
Publications, 2004.
PERIODICALS

Roberts, Shauna S. ‘‘Options Increase for Men With
Erectile Dysfunction: Doctors Now Have an
Array of Treatments for Men’s Sexual
Problems.’’ Diabetes Forecast (September
2004): 55-58.
Sadovsky, Richard. ‘‘Sildenafil is Safe and Effective in Men
With Stable CAD.’’ American Family Physician
(September 1, 2004): 955.
Tomlinson, John. ‘‘The Patient With Erectile
Dysfunction.’’ The Practitioner (February
9, 2005): 104.
Trissel, Lawrence A. ‘‘Long-Term Stability of Trimix: A
Three-Drug Injection Used to Treat Erectile
Dysfunction.’’ International Journal of
Pharmaceutical Compounding (May-June
2004): 231-235.
Wooten, James M. ‘‘Erectile Dysfunction: There are Now
Three Effective Oral Drugs for Treating ED, Paving
the Way for Nurses to Put Patients With This
Condition on the Road to Good Sexual Health.’’ RN
(October 2004): 40.
1366

Erysipelas
Definition
Erysipelas is a skin infection that often follows
strep throat.

Description
Erysipelas, also called St. Anthony’s fire, is caused
by infection by Group A Streptococci. This same type
of bacteria is responsible for such infections as strep
throat, and infections of both surgical and other kinds
of wounds in the skin. The infection occurs most often
in young infants and the elderly.

Causes and symptoms
Erysipelas usually occurs rather abruptly. When
the preceding infection was strep throat, the rash
begins on the face. Occasionally, when the preceding
infection was of a wound from an injury or operation,
the rash will appear on an arm or leg.
Classically, the usual presentation is a bright-red,
butterfly-shaped rash appearing across the bridge of the
nose and the cheeks. It is hot to the touch, painful, shiny,
and swollen, with clearly defined margins. The edges of
the rash are a raised ridge, hard to the touch. There may
be fluid-filled bumps scattered along the area. The rash
spreads rapidly. Some patients have swelling of the eyelids, sometimes so severe that their eyes swell shut. The
patient may have fever, chills, loss of energy, nausea and
vomiting, and swollen, tender lymph nodes. In severe
GALE ENCYCLOPEDIA OF MEDICINE

Bacteremia—The presence of bacteria in the
blood.
Streptococcus—A bacteria that causes erysipelas
and strep throat, as well as other infections.

cases, walled-off areas of pus (abscesses) may develop
beneath the skin. If left untreated, the streptococcal
bacteria may begin circulating in the bloodstream
(a condition called bacteremia). A patient may then
develop an overwhelming, systemic infection called
sepsis, with a high risk of death.

Diagnosis
The rash of erysipelas is very characteristic, raising the practitioner’s suspicion towards that diagnosis,
especially when coupled with a history of recent strep
infection. Attempts to culture (grow) the bacteria from
a sample of the rash usually fail. When the bacteria are
present in the blood, they may be grown in a laboratory, and identified under a microscope. Other laboratory tests involve reacting fluorescently-tagged
antibodies with a sample of the patient’s infected tissue. This type of test may be successful in positively
identifying the streptococcal bacteria.

Treatment
Penicillin is the drug of choice for treating erysipelas. It can usually be given by mouth, although
in severe cases (or in cases of diagnosed bacteremia)
it may be given through a needle placed in a vein
(intravenously).
Even with antibiotic treatment, swelling may continue to spread. Other symptoms, such as fever, pain,
and redness, usually decrease rapidly after penicillin is
started. Cold packs and pain relievers may help
decrease discomfort. Within about five to 10 days,
the affected skin may begin drying up and flaking off.

Prognosis
With prompt treatment, the prognosis from
erysipelas is excellent. Delay of treatment, however,
increases the chance for bacteremia and the potential for death from overwhelming sepsis. This is
particularly true of people with weakened immune
systems (babies, the elderly, and people ill with other
diseases, especially Acquired Immunodeficiency
GALE ENCYCLOPEDIA OF MEDICINE

Syndrome, or AIDS). Frequently, an individual
who has had erysipelas will have it occur again in
the same location.

Prevention
Prevention involves appropriate and complete
treatment of streptococcal infections, including strep
throat and wound infections.
Resources
PERIODICALS

Huerter, Christopher, et al. ‘‘Helpful Clues to Common
Rashes.’’Patient Care 31, no. 8 (April 30, 1997): 9+.

Rosalyn Carson-DeWitt, MD

Erythema infectiosum see Fifth disease

Erythema multiforme
Definition
Erythema multiforme is a skin disease that causes
lesions and redness around the lesions.

Description
Erythema multiforme appears on the skin and the
mucous membranes (the lining of the mouth, digestive
tract, vagina, and other organs). Large, symmetrical
red blotches appear all over the skin in a circular
pattern. On mucous membranes, it begins as blisters
and progresses to ulcers. A more advanced form,
called Stevens-Johnson syndrome, can be severe and
even fatal.

Causes and symptoms
Erythema multiforme has many causes, most
commonly are drugs. Penicillin, sulfonamides, certain
epilepsy drugs, aspirin, and acetaminophen are the
most likely medication-induced causes. Erythema
multiforme can also be caused by certain diseases.
Herpes virus and mycoplasma pneumonia are likely
infectious causes.

Diagnosis
The appearance of the rash is sufficiently unique
to identify it on sight. Having identified it, the physician will determine the underlying cause.
1367

Erythema multiforme

KEY TERMS

Erythroblastosis fetalis

KEY TERMS

KEY TERMS

Herpes virus—Viruses that can infect the skin,
mucous membranes, and brain, and they are
responsible for such diseases as herpes simplex,
chicken pox, and shingles.
Mycoplasma pneumonia—An incomplete bacterium that infects the lung.

Biopsy—Surgical removal of tissue for diagnostic
purposes.
Panniculitis—Inflammation of fatty tissue.

Treatment
Erythema multiforme is inadvertently treated
when the causative agent, whether it be a drug or a
disease, is treated. In severe cases, cortisone-like medication is often used along with general supportive
measures and prevention of infection.

Prognosis
As a rule, the rash abates by itself without damaging the skin. Only in the case of infection, severe
blistering, or continued use of an offending drug
does complications occur.
Resources

tuberculosis, several fungal lung infections, leprosy,
inflammatory bowel disease, and some potentially
dangerous bacterial infections. Drugs can also induce
erythema nodosum. The most common are penicillin,
sulfonamides, and birth control pills.

Diagnosis
There are a few other skin eruptions that mimic
erythema nodosum, so the physician may have to perform a biopsy to sort them out. There are a few types
of panniculitis, fat inflammation, that may signal a
cancer somewhere in the body, and there are other
kinds of inflammation that may confuse the diagnosis.
Once the skin problem has been diagnosed, its
underlying cause must then be identified. A lengthy
evaluation may ensue, and often times the cause
remains unknown.

BOOKS

Fauci, Anthony S., et al., editors. Harrison’s
Principles of Internal Medicine. New York:
McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Treatment
Painful nodules can be treated with mild pain killers and local application of ice packs. Medical attention will be directed toward the underlying disease.
The nodules will eventually disappear, leaving no
trace behind.
Resources

Erythema nodosum
Definition

BOOKS

Bennett, J. Claude, and Fred Plum, editors. Cecil Textbook
of Medicine. Philadelphia: W. B. Saunders Co., 1996.

Erythema nodosum is a skin disorder characterized
by painful red nodules appearing mostly on the shins.

Description
Erythema nodosum is an eruption of tender red
lumps on both shins and occasionally the arms and
face. Bruising often accompanies the nodule formation.
Erythema nodosum is most prevalent in young adults.

Causes and symptoms
Erythema nodosum can be caused by many
important and treatable diseases. Among them are
1368

J. Ricker Polsdorfer, MD

Erythremia see Polycythemia vera

Erythroblastosis fetalis
Definition
Erythroblastosis fetalis refers to two potentially
disabling or fatal blood disorders in infants: Rh
GALE ENCYCLOPEDIA OF MEDICINE

Description
Red blood cells carry several types of proteins,
called antigens, on their surfaces. The A, B, and O
antigens are used to classify a person’s blood as type
A, B, AB, or O. Each parent passes one A, B, or O
antigen gene to their child. How the genes are paired
determines the person’s blood type.
A person who inherits an A antigen gene from
each parent has type A blood; receiving two B antigen
genes corresponds with type B blood; and inheriting A
and B antigen genes means a person has type AB
blood. If the O antigen gene is inherited from both
parents, the child has type O blood; however, the
pairing of A and O antigen genes corresponds with
type A blood; and if the B antigen gene is matched
with the O antigen gene, the person has type B blood.
Another red blood cell antigen, called the Rh
factor, also plays a role in describing a person’s
blood type. A person with at least one copy of the
gene for the Rh factor has Rh-positive blood; if no
copies are inherited, the person’s blood type is
Rh-negative. In blood typing, the presence of A, B,
and O antigens, plus the presence or absence of the
Rh-factor, determine a person’s specific blood type,
such as A-positive, B-negative, and so on.
A person’s blood type has no effect on health.
However, an individual’s immune system considers
only that person’s specific blood type, or a close
match, acceptable. If a radically different blood type
is introduced into the bloodstream, the immune system produces antibodies, proteins that specifically
attack and destroy any cell carrying the foreign
antigen.
Determining a person’s blood type is very important if she becomes pregnant. Blood cells from the
unborn baby (fetal red blood cells) can cross over
into the mother’s bloodstream, especially at delivery.
If the mother and her baby have compatible blood
types, the crossover does not present any danger.
However, if the blood types are incompatible, the
GALE ENCYCLOPEDIA OF MEDICINE

mother’s immune system manufactures antibodies
against the baby’s blood.
Usually, this incompatibility is not a factor in a
first pregnancy, because few fetal blood cells reach the
mother’s bloodstream until delivery. The antibodies
that form after delivery cannot affect the first child. In
later pregnancies, fetuses and babies may be in grave
danger. The danger arises from the possibility that the
mother’s antibodies will attack the fetal red blood
cells. If this happens, the fetus or baby can suffer
severe health effects and may die.
There are two types of incompatibility diseases:
Rh incompatibility disease and ABO incompatibility
disease. Both diseases have similar symptoms, but Rh
disease is much more severe, because anti-Rh antibodies cross over the placenta more readily than anti-A
or anti-B antibodies. (The immune system does not
form antibodies against the O antigen.) Therefore, a
greater percentage of the baby’s blood cells are
destroyed by Rh disease.
Both incompatibility diseases are uncommon in
the United States due to medical advances over the last
50 years. For example, prior to 1946 (when newborn
blood transfusions were introduced) 20,000 babies
were affected by Rh disease yearly. Further advances,
such as suppressing the mother’s antibody response,
have reduced the incidence of Rh disease to approximately 4,000 cases per year.
Rh disease only occurs if a mother is Rh-negative
and her baby is Rh-positive. For this situation to
occur, the baby must inherit the Rh factor gene from
the father. Most people are Rh-positive. Only 15% of
the Caucasian population is Rh-negative, compared to
5–7% of the African-American population and virtually none of Asian populations.
ABO incompatibility disease is almost always limited to babies with A or B antigens whose mothers
have type O blood. Approximately one third of these
babies show evidence of the mother’s antibodies in
their bloodstream, but only a small percentage
develop symptoms of ABO incompatibility disease.

Cause and symptoms
Rh disease and ABO incompatibility disease are
caused when a mother’s immune system produces
antibodies against the red blood cells of her unborn
child. The antibodies cause the baby’s red blood cells
to be destroyed and the baby develops anemia. The
baby’s body tries to compensate for the anemia by
releasing immature red blood cells, called erythroblasts, from the bone marrow.
1369

Erythroblastosis fetalis

incompatibility disease and ABO incompatibility disease. Either disease may be apparent before birth and
can cause fetal death in some cases. The disorder is
caused by incompatibility between a mother’s blood
and her unborn baby’s blood. Because of the incompatibility, the mother’s immune system may launch an
immune response against the baby’s red blood cells.
As a result, the baby’s blood cells are destroyed, and
the baby may suffer severe anemia (deficiency in red
blood cells), brain damage, or death.

Erythroblastosis fetalis

The overproduction of erythroblasts can cause the
liver and spleen to become enlarged, potentially causing liver damage or a ruptured spleen. The emphasis
on erythroblast production is at the cost of producing
other types of blood cells, such as platelets and other
factors important for blood clotting. Since the blood
lacks clotting factors, excessive bleeding can be a
complication.
The destroyed red blood cells release the blood’s
red pigment (hemoglobin) which degrades into a yellow substance called bilirubin. Bilirubin is normally
produced as red blood cells die, but the body is only
equipped to handle a certain low level of bilirubin in
the bloodstream at one time. Erythroblastosis fetalis
overwhelms the removal system, and high levels of
bilirubin accumulate, causing hyperbilirubinemia, a
condition in which the baby becomes jaundiced. The
jaundice is apparent from the yellowish tone of the
baby’s eyes and skin. If hyperbilirubinemia cannot be
controlled, the baby develops kernicterus. The term
kernicterus means that bilirubin is being deposited in
the brain, possibly causing permanent damage.
Other symptoms that may be present include high
levels of insulin and low blood sugar, as well as a
condition called hydrops fetalis. Hydrops fetalis is
characterized by an accumulation of fluids within the
baby’s body, giving it a swollen appearance. This fluid
accumulation inhibits normal breathing, because the
lungs cannot expand fully and may contain fluid. If
this condition continues for an extended period, it can
interfere with lung growth. Hydrops fetalis and anemia can also contribute to heart problems.

Diagnosis

Treatment
When a mother has antibodies against her unborn
infant’s blood, the pregnancy is watched very carefully. The antibodies are monitored and if levels
increase, amniocentesis, fetal umbilical cord blood
sampling, and ultrasound are used to assess any effects
on the baby. Trouble is indicated by high levels of
bilirubin in the amniotic fluid or baby’s blood, or if
the ultrasound reveals hydrops fetalis. If the baby is in
danger, and the pregnancy is at least 32–34 weeks
along, labor is induced. Under 32 weeks, the baby is
given blood transfusions while still in the mother’s
uterus.
There are two techniques that are used to deliver a
blood transfusion to a baby before birth. In the first, a
needle is inserted through the mother’s abdomen and
uterus, and into the baby’s abdomen. Red blood cells
injected into the baby’s abdominal cavity are absorbed
into its bloodstream. In early pregnancy or if the
baby’s bilirubin levels are gravely high, cordocentesis
is performed. This procedure involves sliding a very
fine needle through the mother’s abdomen and, guided
by ultrasound, into a vein in the umbilical cord to
inject red blood cells directly into the baby’s
bloodstream.
After birth, the severity of the baby’s symptoms
are assessed. One or more transfusions may be necessary to treat anemia, hyperbilirubinemia, and bleeding. Hyperbilirubinemia is also treated with
phototherapy, a treatment in which the baby is placed
under a special light. This light causes changes in how
the bilirubin molecule is shaped, which makes it easier
to excrete. The baby may also receive oxygen and
intravenous fluids containing electrolytes or drugs to
treat other symptoms.

Erythroblastosis fetalis can be predicted before
birth by determining the mother’s blood type. If she
is Rh-negative, the father’s blood is tested to determine whether he is Rh-positive. If the father is
Rh-positive, the mother’s blood will be checked for
antibodies against the Rh factor. A test that demonstrates no antibodies is repeated at week 26 or 27 of the
pregnancy. If antibodies are present, treatment is
begun.

In many cases of blood type incompatibility, the
symptoms of erythroblastosis fetalis are prevented
with careful monitoring and blood type screening.
Treatment of minor symptoms is typically successful
and the baby will not suffer long-term problems.

In cases in which incompatibility is not identified
before birth, the baby suffers recognizable characteristic symptoms such as anemia, hyperbilirubinemia,
and hydrops fetalis. The blood incompatibility is
uncovered through blood tests such as the Coombs
test, which measures the level of maternal antibodies
attached to the baby’s red blood cells. Other blood
tests reveal anemia, abnormal blood counts, and high
levels of bilirubin.

Nevertheless, erythroblastosis is a very serious
condition for approximately 4,000 babies annually.
In about 15% of cases, the baby is severely affected
and dies before birth. Babies who survive pregnancy
may develop kernicterus, which can lead to deafness,
speech problems, cerebral palsy, or mental retardation. Extended hydrops fetalis can inhibit lung growth
and contribute to heart failure. These serious complications are life threatening, but with good medical

1370

Prognosis

GALE ENCYCLOPEDIA OF MEDICINE

Amniocentesis—A procedure in which a needle is
inserted through a pregnant woman’s abdomen
and into her uterus to withdraw a small sample of
amniotic fluid. The amniotic fluid can be examined
for sign of disease or other problems afflicting the
fetus.
Amniotic fluid—The fluid that surrounds a fetus in
the uterus.
Anemia—A condition in which there is an abnormally low number of red blood cells in the bloodstream. Major symptoms are paleness, shortness of
breath, unusually fast or strong heart beats, and
tiredness.
Antibody—A protein molecule produced by the
immune system in response to a protein that is not
recognized as belonging in the body.
Antigen—A protein that can elicit an immune
response in the form of antibody formation. With
regard to red blood cells, the major antigens are A,
B, O, and the Rh factor.
Bilirubin—A yellow-colored end-product of hemoglobin degradation. It is normally present at very
low levels in the bloodstream; at high levels, it
produces jaundice.

treatment, the fatality rate is very low. According to
the U.S. Centers for Disease Control and Prevention,
there were 21 infant deaths in the United States during
1996 that were attributable to hemolytic disease (erythroblastosis fetalis) and jaundice.

Prevention
With any pregnancy, whether it results in a live
birth, miscarriage, stillbirth, or abortion, blood typing
is a universal precaution against blood compatibility
disease. Blood types cannot be changed, but adequate
forewarning allows precautions and treatments that
limit the danger to unborn babies.
If an Rh-negative woman gives birth to an
Rh-positive baby, she is given an injection of immunoglobulin G, a type of antibody protein, within
72 hours of the birth. The immunoglobulin destroys
any fetal blood cells in her bloodstream before her
immune system can react to them. In cases where this
precaution is not taken, antibodies are created and
future pregnancies may be complicated.
Resources
PERIODICALS

Bowman, John. ‘‘The Management of Hemolytic Disease in
the Fetus and Newborn.’’ Seminars in Perinatology 21,
no. 1 (February 1997): 39.

Cordocentesis—A procedure for delivering a blood
transfusion to a fetus. It involves a fine needle being
threaded through a pregnant woman’s abdomen
and into the umbilical cord with the aid of ultrasound imaging.
Hemoglobin—A molecule in red blood cells that
transports oxygen and gives the cells their characteristic color.
Hydrops fetalis—A condition in which a fetus or
newborn baby accumulates fluids, causing swollen
arms and legs and impaired breathing.
Hyperbilirubinemia—A condition in which bilirubin accumulates to abnormally high levels in the
bloodstream
Placenta—A protective membrane that surrounds
and protects the fetus during pregnancy.
Platelet—A blood factor that is important in forming blood clots.
Rh factor—An antigen that is found on the red
blood cells of most people. If it is present, the
blood type is referred to as Rh-positive; if absent,
the blood type is Rh-negative.

GALE ENCYCLOPEDIA OF MEDICINE

Julia Barrett

Erythrocyte sedimentation
rate
Definition
The erythrocyte sedimentation rate (ESR), or
sedimentation rate (sed rate), is a measure of the settling of red blood cells in a tube of blood during one
hour. The rate is an indication of inflammation and
increases in many diseases.

Purpose
ESR is increased in rheumatoid diseases, most
infections, and in cancer. An advanced rate doesn’t
diagnose a specific disease, but it does indicate that an
underlying disease may be present.
A physician can use ESR to monitor a person with
an associated disease. When the disease worsens, the
1371

Erythrocyte sedimentation rate

KEY TERMS

Erythrocyte sedimentation rate

ESR increases; when the disease improves, the ESR
decreases. The ESR doesn’t always follow the course
of cancer.
ESR is called an acute-phase reactant test, meaning that it reacts to acute conditions in the body, such
as infection or trauma. The rate increase follows a rise
in temperature and white blood cells count, peaks after
several days, and usually lasts longer than the elevated
temperature or white blood cells count.

Precautions
The ESR should not be used to screen healthy
persons for disease.

KEY TERMS
Acute phase reactant—A substance in the blood
that increases as a response to an acute conditions
such as infection, injury, tissue destruction, some
cancers, burns, surgery, or trauma.
Erythrocyte sedimentation rate (ESR)—The
distance that red blood cells settle in a tube of
blood in one hour. It is an indication of
inflammation.
Rouleaux—The stacking up of red blood cells,
caused by extra or abnormal proteins in the blood
that decrease the normal distance red cells maintain between each other.

Description
The ESR test is a simple test dating back to the
ancient Greeks. A specific amount of diluted,
unclotted blood is placed in a special narrow tube
and left undisturbed for exactly one hour. The red
cells settle towards the bottom of the tube, and the
pale yellow liquid (plasma) rises to the top. After 60
minutes, measurements are taken of the distance the
red cells traveled to settle at the bottom of the tube.
Two methods, the Westergren and the Wintrobe, are
used by laboratories; each method produces slightly
different results. Most laboratories use the Westergren
method.
Normally red cells don’t settle far toward the
bottom of the tube. Many diseases make extra or
abnormal proteins that cause the red cells to move
close together, stack up, and form a column (rouleaux). In a group, red cells are heavier and fall faster.
The faster they fall, the further they settle, and the
higher the ESR.
The ESR test is covered by insurance when medically necessary. Results are usually available the same
or following day.

Preparation
This test requires 7mL–10 mL of blood. A healthcare worker ties a tourniquet on the patient’s upper
arm, locates a vein in the inner elbow region, and
inserts a needle into that vein. Vacuum action draws
the blood through the needle into an attached tube.
Collection of the sample takes only a few minutes.

Aftercare
Discomfort or bruising may occur at the puncture
site. Pressure applied to the puncture site until the
1372

bleeding stops reduces bruising. Warm packs to the
puncture site relieve discomfort. The patient may feel
dizzy or faint.

Normal results
A normal value does not rule out disease. Normal
values for the Westergren method are: Men 0 mm/
hour–15 mm/hour; women 0 mm/hour–20 mm/hour;
and children 0 mm/hour–10 mm/hour.

Abnormal results
The highest ESR levels are usually seen in a cancer
of a certain type of white blood cell (multiple myeloma)
and rheumatoid disease, such as rheumatoid arthritis.
Many other diseases also increase the ESR: infection,
kidney disease, anemia, diseases involving white blood
cells, cancer, and autoimmune and inflammatory
diseases.
Any disease that changes the shape and size of red
blood cells decreases the ESR. Distorted cells, such as
with sickle cell disease, do not stack, and consequently
do not settle far, even in the presence of an ESRassociated disease. Diseases that cause the body to
make less protein or extra red blood cells also decrease
the ESR.
Resources
PERIODICALS

Saadeh, Constantine. ‘‘The Erythrocyte Sedimentation
Rate: Old and New Clinical Applications.’’ Southern
Medical Journal March 1998: 220-255.

Nancy J. Nordenson
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Erythromycins are medicines that kill bacteria or
prevent their growth.

Precautions
Purpose
Erythromycins are antibiotics, medicines used to
treat infections caused by microorganisms. Physicians
prescribe these drugs for many types of infections
caused by bacteria, including strep throat, sinus infections, pneumonia, ear infections, tonsillitis, bronchitis,
gonorrhea, pelvic inflammatory disease (PID), and
urinary tract infections. Some medicines in this
group are also used to treat Legionnaires’ disease and
ulcers caused by bacteria. These drugs will not work
for colds, flu, and other infections caused by viruses.

Symptoms should begin to improve within a few
days of beginning to take this medicine. If they do not,
or if they get worse, check with the physician who
prescribed the medicine.
Erythromycins may cause mild diarrhea, that
usually goes away during treatment. However, severe
diarrhea could be a sign of a very serious side effect.
Anyone who develops severe diarrhea while taking
erythromycin or related drugs should stop taking the
medicine and call a physician immediately.
Special conditions

Description
The drugs described here include erythromycins
(Erythrocin, Ery-C, E-Mycin, and other brands) and
medicines that are chemically related to erythromycins, such as azithromycin (Zithromax) and clarithromycin (Biaxin). They are available only with a
physician’s prescription and are sold in capsule, tablet
(regular and chewable), liquid, and injectable forms.

Recommended dosage
The recommended dosage depends on the type of
erythromycin, the strength of the medicine, and the
medical problem for which it is being taken. Check
with the physician who prescribed the drug or the pharmacist who filled the prescription for the correct dosage.
Always take erythromycins exactly as directed.
Never take larger, smaller, more frequent, or less frequent doses. To make sure the infection clears up
completely, it is very important to take the medicine
for as long as it has been prescribed. Do not stop
taking the drug just because symptoms begin to
improve. This is important with all types of infections,
but it is especially important in ‘‘strep’’ infections,
which can lead to serious heart problems if they are
not cleared up completely.
Erythromycins work best when they are at constant levels in the blood. To help keep levels constant,
take the medicine in doses spaced evenly through the
day and night. Do not miss any doses. Some of these
medicines are most effective when taken with a full
glass of water on an empty stomach, but they may be
GALE ENCYCLOPEDIA OF MEDICINE

Taking erythromycins may cause problems for
people with certain medical conditions or people who
are taking certain other medicines. Before taking these
drugs, be sure to let the physician know about any of
these conditions:
ALLERGIES. Anyone who has had unusual reactions to erythromycins, azithromycin, or clarithromycin in the past should let his or her physician know
before taking the drugs again. The physician should
also be told about any allergies to foods, dyes, preservatives, or other substances.
PREGNANCY. Some medicines in this group may
cause problems in pregnant women and have the
potential to cause birth defects. Women who are pregnant or who may become pregnant should check with
their physicians before taking these drugs.
BREASTFEEDING. Erythromycins pass into breast
milk. Mothers who are breastfeeding and who need
to take this medicine should check with their
physicians.
OTHER MEDICAL CONDITIONS. Before using erythromycins, people with any of these medical problems should make sure their physicians are aware of
their conditions:


heart disease



liver disease



hearing loss

USE OF CERTAIN MEDICINES. Taking erythromycins with certain other drugs may affect the way the
drugs work or may increase the chance of side effects.

1373

Erythromycins

Erythromycins

taken with food if stomach upset is a problem. Others
work equally well when taken with or without food.
Check package directions or ask the physician or
pharmacist for instructions on how to take the
medicine.

Erythromycins

KEY TERMS
Bronchitis—Inflammation of the air passages of the
lungs.
Gonorrhea—A sexually transmitted disease (STD)
that causes infection in the genital organs and may
cause disease in other parts of the body.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Legionnaire’s disease—A lung disease caused by a
bacterium.
Microorganism—An organism that is too small to
be seen with the naked eye.
Pelvic inflammatory disease (PID)—Inflammation
of the female reproductive tract, caused by any of
several microorganisms. Symptoms include severe
abdominal pain, high fever, and vaginal discharge.
Severe cases can result in sterility.
Pneumonia—A disease in which the lungs become
inflamed. Pneumonia may be caused by bacteria,
viruses, or other organisms, or by physical or chemical irritants.
Sinus—Any of several air-filled cavities in the
bones of the skull.
Strep throat—A sore throat caused by infection
with Streptococcus bacteria. Symptoms include
sore throat, chills, fever, and swollen lymph nodes
in the neck.
Tonsillitis—Inflammation of a tonsil, a small mass
of tissue in the throat.
Urinary tract—The passage through which urine
flows from the kidneys out of the body.

Side effects
The most common side effects are mild diarrhea,
nausea, vomiting, and stomach or abdominal cramps.
These problems usually go away as the body adjusts to
the drug and do not require medical treatment. Less
common side effects, such as sore mouth or tongue
and vaginal itching and discharge also may occur and
do not need medical attention unless they persist or are
bothersome.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with a physician immediately:


severe stomach pain, nausea, vomiting, or diarrhea



fever

1374



skin rash, redness, or itching



unusual tiredness or weakness

Although rare, very serious reactions to azithromycin (Zithromax) are possible, including extreme
swelling of the lips, face, and neck, and anaphylaxis
(a violent allergic reaction). Anyone who develops
these symptoms after taking azithromycin should
stop taking the medicine and get immediate medical
help.
Other rare side effects may occur with erythromycins and related drugs. Anyone who has unusual
symptoms after taking these medicines should get in
touch with his or her physician.

Interactions
Erythromycins may interact with many other
medicines. When this happens, the effects of one or
both of the drugs may change or the risk of side effects
may be greater. Anyone who takes erythromycins
should let the physician know all other medicines he
or she is taking. Among the drugs that may interact
with erythromycins are:


acetaminophen (Tylenol)



medicine for overactive thyroid



male hormones (androgens)



female hormones (estrogens)



other antibiotics



blood thinners



disulfiram (Antabuse), used to treat alcohol abuse



antiseizure medicines
(Depakote, Depakene)



caffeine



the antihistamines astemizole (Hismanal)



antiviral drugs such as (zidovudine) Retrovir

such

as

valproic

acid

The list above does not include every drug that
may interact with erythromycins. Be sure to check
with a physician or pharmacist before combining erythromycins with any other prescription or nonprescription (over-the-counter) medicine.
Nancy Ross-Flanigan

Erythropoietin see Cancer therapy,
supportive; Immunologic therapies
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Erythropoietin, also called EPO, is a type of
protein called a glycoprotein that is formed mainly
in the kidneys to stimulate the production of red
blood cells.

Purpose
The erythropoietin (EPO) test is used to determine if hormonal secretion is causing changes in the
red blood cells. The test has great value in evaluating
low hemoglobin (anemia), and another disorder
called polycythemia, in which unusually large numbers of red blood cells are found in the blood. The
EPO test is also used to identify kidney tumors
and identify or assess kidney disease It also may be
used to evaluate abuse by athletes who believe
commercially prepared erythropoietin enhances
performance.

Precautions
Not every laboratory is equipped to evaluate
EPO, so the reference laboratory (a large commercial
lab that does tests for hospitals not equipped to do
them) performing the test may require as many as four
days to complete the analysis. It should also be noted
that EPO values increase in pregnancy, in which significantly higher levels are found before the twentyfourth week.

Kidney disease can cause anemia and many
patients on kidney dialysis will require monthly EPO
tests to check their hemoglobin levels.
Some athletes use EPO to enhance performance,
as the increased red cell volume adds more oxygencarrying capacity to the blood. Adverse reactions to
this practice can include clotting abnormalities, headache, seizures, high blood pressure, nausea, vomiting,
diarrhea, and rash.

Preparation
The EPO test requires a blood sample. The patient
is to fast with nothing to eat or drink for at least eight
hours before the test. It is also suggested that the
patient lie down for 30 minutes before the test.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or feeling lightheaded after venipuncture,
and hematoma (blood accumulating under the
puncture site).

Description
Erythropoietin is produced primarily in the kidneys but interacts with other factors in the bone marrow to increase red cell production. EPO is unique
among the blood cell growth factors, because it is the
only one that behaves like a hormone.
Erythropoietin acts as the principal regulator in
the production of red blood cells (erythrocytes) by
controlling the number, the kinds, and the survival
of the cells. Because of this ability, it is being investigated for use in cancer patients to prevent anemia
(hemoglobin concentration in the blood is lower
than normal), or to treat anemia that has been
induced by chemotherapy and bone marrow transplantation (BMT).
The correction of anemia can result in reduced
transfusion requirements, so the erythropoietin test is
used to diagnose anemia, including the anemia of endGALE ENCYCLOPEDIA OF MEDICINE

Normal results
Reference values vary from laboratory to laboratory, but a general normal range is 11–48 mU/ml
(milliunits per milliliter).

Abnormal results
Low levels of EPO are found in anemic patients
with inadequate or absent production of erythropoietin. Severe kidney disease may decrease production of EPO, and congenital absence of EPO can
occur.
Elevated levels of EPO can be found in some
anemias when the body tries to overcompensate for
reduced blood volume. Elevated levels are also seen
in polycythemia, and erythropoietin-secreting
tumors.
1375

Erythropoietin test

Erythropoietin test

stage renal disease. Erythropoietin determination is
also valuable in diagnosing a condition known as
polycythemia, when increased numbers of red blood
cells occur. Levels of erythropoietin are extremely low
in polycythemia vera but are normal or high in secondary polycythemia. It happens rarely, but cysts in the
liver or kidneys, as well as tumors in the kidneys or
brain, can also produce erythropoietin. Patients with
these conditions can have high levels of erythropoietin
and may develop secondary polycythemia.

Escherichia coli

KEY TERMS
Anemia—A condition in which the hemoglobin
concentration in the blood is below normal.
Polycythemia vera—A condition characterized by
an unusually large number of red blood cells in the
blood due to increased production by the bone
marrow. Symptoms include headaches, blurred
vision, high blood pressure, dizziness, and night
sweats.
Secondary polycythemia—Secondary polycythemia occurs when the excess of red blood cells is
caused by a condition other than polycythemia
vera. For example, when low levels of oxygen in
the blood stimulate the bone marrow to produce
more red blood cells, as in chronic lung disease.

Resources
PERIODICALS

‘‘GP Clinical: Anemia in Kidney Disease.’’ GP November 5,
2004: 66.

Janis O. Flores
Teresa G. Odle

ESB see Electrical stimulation of the brain

Escherichia coli
Definition
E. coli (Escherichia coli) is one of several types of
bacteria that normally inhabit the intestine of humans
and animals (commensal organism). Some strains of
E. coli are capable of causing disease under certain
conditions when the immune system is compromised
or disease may result from an environmental exposure.

Description
E. coli bacteria may give rise to infections in
wounds, the urinary tract, biliary tract, and abdominal
cavity (peritonitis). This organism may cause septicemia, neonatal meningitis, infantile gastroenteritis,
tourist diarrhea, and hemorrhagic diarrhea. An
E. coli infection may also arise due to environmental
exposure. Infections with this type of bacteria pose a
serious threat to public health with outbreaks arising
1376

from food and water that has been contaminated with
human or animal feces or sewage. This type of bacteria
has been used as a biological indicator for safety of
drinking water since the 1890s. Exposure may also
occur during hospitalization, resulting in pneumonia
in immunocompromised patients or those on a
ventilator

Causes and symptoms
The symptoms of infection and resulting complications are dependent upon the strain of E. coli and the
site of infection. These bacteria produce toxins that
have a wide range of effects. Symptoms caused by
some E. coli infections range from mild to severe,
bloody diarrhea, acute abdominal pain, vomiting, and
fever. Gastrointestinal complications that can cause
E. coli infections include irritable bowel syndrome
(IBS) ischemic colitis, appendicitis, perforation of the
large bowel, and in some instances gangrene in the
colon. Other known E. coli-causing infections may
include chronic renal failure, pancreatitis, and diabetes
mellitus. Some neurological symptoms such as drowsiness, seizure and coma may occur. In infants, E. coli
infections are present in cases of infantile gastroenteritis and neonatal meningitis.
Strains of E. coli that produce diarrhea were initially distinguished by their O (somatic) antigens found
on the bacterial surface. Although there is an overlap
in characteristics between strains, they may be classified into four main groups; enterohemorrahagic
(0157),enteropathogenic (055,0111), enterotoxigenic
(06,078), and enteroinvasive (0124,0164).
E.coli O157 (VTEC)
The O157:H7 strain is the member of the group
most often associated with a particularly severe form
of diarrhea. (The O indicates the somatic antigen,
while the H denotes the flagellar antigen, both of
which are found on the cell surface of the bacteria.)
The bacterium was discovered in 1977, and first
reports of infections followed in 1982. E. coli
O157:H7, as it is frequently referred to by researchers,
causes bloody diarrhea in many infected patients. It
accounts for about 2% of all cases of diarrhea in the
western world, and at least one-third of cases of
hemorrhagic colitis, or about 20,000 cases per year
E. coli O157:H7 is also the most common cause of
unique syndromes, known as the Hemolytic-Uremic
Syndrome (HUS) and thrombocytopenic purpura
(TTP), which causes kidney failure, hemolytic anemia,
and thrombocytopenia. Usually, infection with this
strain of bacteria will subside without further
GALE ENCYCLOPEDIA OF MEDICINE

This strain of bacteria produces a potent toxin
called verotoxin, named for toxin’s ability to kill
green monkey kidney or ‘‘vero’’ cells. Bacteria that
produce verotoxin are referred to as Verotoxin-producing E. coli (VTEC). The numbers of bacteria that
are necessary to reproduce infectious levels of bacteria are quite small, estimated at 10-100 viable bacteria. These toxins are lethal for intestinal cells and
those that line vessels (endothelial cells), inhibiting
protein synthesis causing cell death. It is believed
that the damage to blood vessels results in the formation of clots, which eventually leads to the
Hemolytic-Uremic Syndrome. HUS/TTP is a serious, often fatal, syndrome that has other causes in
addition to E. coli O157:H7; it is characterized by the
breaking up of red blood cells (hemolysis) and kidney failure (uremia). The syndrome occurs most
often in the very young and very old.
E. coli O157:H7 is commonly found in cattle and
poultry, and outbreaks have of disease have been
associated with cattle and bovine products. There are
reports of contamination from unpasteurized apple
juice, hamburger meat, radish sprouts, lettuce, and
potatoes, as well as other food sources. Environmental
contamination may occur in water drained from cattle
pastures or water containing human sewage used for
drinking or swimming. Human to human transmission,
through contact with fecal matter, has also been identified in daycare centers.
After an incubation period of three to four days on
average, watery diarrhea begins, which rapidly progresses to bloody diarrhea in many victims, in which
case the bowel movement may be mostly blood.
Nausea, vomiting, and low-grade fever are also frequently present. Gastrointestinal symptoms last for
about one week, and recovery is often spontaneous.
Symptomatic infection may occur in about 10% of
infected individuals. About 5-10% of individuals,
usually at the extremes of age or elevated leukocyte
count, develop HUS/TTP, and ultimately, kidney failure. Patients taking antibiotics or medications for gastric acidity may also be at risk. Neurological symptoms
can also occur as part of HUS/TTP and consist of
seizures, paralysis, and coma. Rectal prolapse may
also be a complication, and in some cases colitis,
appendicitis, perforation of the large bowel, and gangrene in the bowel. Systemically, the most prevalent
complications of E. coli 157 infections are HUS
and TTP.
GALE ENCYCLOPEDIA OF MEDICINE

Escherichia coli

complications. However, about 5% of people who are
infected will develop HUS/TTP. This infection also
accounts for the majority of episodes of HUS, especially in children.

A magnified image of the E. coli bacterium. (The Stock Market.
Reproduced by permission.)

E. coli non-O157 (VTEC)
These strains of E. coli produce verotoxin, but are
strains other than O157. There have been as many as
one hundred different types implicated in the development of disease. Strain OH111 was found to be
involved in outbreaks in Australia, Japan, and Italy.
The O128, O103, and O55 groups have also been
implicated in diarrhea outbreaks. In Britain, cases of
infantile gastroenteritis in maternity hospitals and
neonatal units have been attributed to the E. coli)
non-0157 group. Many of these organisms have been
identified in cattle.
Enterotoxigenic E. coli
Two toxins may be produced by this group, the
heat-labile enterotoxin (LT) that can produce enteritis
in infants, and a heat stable enterotoxin (ST), the
action of which has yet to be determined.
Enteroinvasive E. coli
Some strains of the enteroinvasive E. coli have
been involved in the development of gastroenteritis
in infants. These organisms do not produce and enterotoxin. The cells of the intestine are affected, with the
development of symptoms that are typical of a shigellae infection.

Diagnosis
Diagnosis of a specific type of infection is dependant upon the characteristics of the particular strain of
the organism.
1377

Escherichia coli

E. coli O157:H7 (HUS)
This particular strain of E. coli is suspected when
bloody diarrhea, bloody stools, lack of fever, elevated
leukocyte count, and abdominal tenderness are present. Stool cultures are used to tentatively identify the
bacteria. Unfortunately, cultures are often negative or
inconclusive if done after 48 hours of symptoms.
Further tests are usually needed, however, for confirmation of infection. This may include a full blood
count, blood film, and tests to determine urea, electrolyte, and LDH (lactate dehydrogenase) levels.
Damaged red blood cells, and elevated levels of creatinine, urea, and LDH with a drop in platelet count may
indicate that HUS will develop. Immunomagnetic
separation is now being used for diagnosis as well.
E. coli non-O157 (VTEC)
Diagnosis is often difficult for these types of bacteria, but production of enterohemolysin (Ehly) is
used as an indicator. Other diagnostic tests are used
to detect verotoxins, including ELISA (enzyme-linked
immunosorbent assays), colony immunoblotting, and
DNA-based tests.

analogues may be helpful. Gentamicin, ampicillin,
ceftazidime, or beta-lactamase-stable cephalosporin
may be administered for neonatal meningitis.
Antibiotic therapy is further complicated by the presence of antibiotic resistant organisms.

Alternative treatment
Studies have been conducted to determine if diarrhea symptoms can be reduced by alternative therapies such as the consumption of herbal teas, psyllium,
and acupuncture. Patients should consult their doctors before using any alternative treatments, as E. coli
can be life threatening and should be closely
monitored.

Prognosis
In most cases of O157:H7, symptoms last for
about a week and recovery is often spontaneous. Ten
percent of individuals with E. coli O157:H7 infection
develop HUS; 5% of those will die of the disease.
Some who recover from HUS will be left with some
degree of kidney damage and possibly irritable bowel
syndrome. Additionally, there is a possibility of
chronic E. coli infection.

E. coli 0157 STEC
Methods for detection of this type of bacteria are
under development, including culture growth media
selective for this organism. Immunomagnetic separation and specific ELISA, latex agglutination tests,
colony immunoblot assays, and other immunological-based detection methods are being explored.

Treatment
Uncomplicated cases of the E. coli O157:H7 the
infection clear up within ten days. It is not certain that
antibiotics are helpful in treating E. coli O157:H7 and
there is some evidence that they may be harmful.
Dehydration resulting from diarrhea must be treated
with either Oral Rehydration Solution (ORS) or intravenous fluids. Anti-motility agents that decrease the
intestines’ ability to contract, should not be used in
any patient with bloody diarrhea. Treatment of HUS,
if it develops, involves correction of clotting factors,
plasma exchange, and kidney dialysis. Blood transfusions may be required. Treatment methods for other
E. coli infections are similar. Antibiotics are often used
in the treatment of E. coli infections, but their role is
controversial. Some antibiotics may enhance the
development of HUS/TTP depending upon their
action, as well as the use of anti diarrhea medications
that should be avoided. Phosphoenolpyruvate
1378

Infants that develop E. coli infections may be
permanently affected. Gastroenteritis may leave the
child with lactose intolerance. Neonates developing
meningitis from E. coli strains have a high morbidity
and mortality rate

Prevention
Thorough cooking of all meat and poultry products and adhering to proper food preparation is the
most effective way to avoid infection. More studies
are needed to determine the appropriate safety margins for killing these bacteria. Food irradiation methods are also being developed to sanitize food.
Vaccinations to E. coli 0157 are under development,
as are medications aimed at limiting the effects of the
verotoxin. The enforcement of regulations for meat
production and water are critical. Steam pasteurization is used in the United States and is being explored
in other countries.
Prevention of E. coli gastroenteritis in infants is
best achieved by breast-feeding. The breast milk contains antibodies that combat the infection. For bottlefed infants, care should be taken in the preparation of
the milk and bottles. Good hygiene of the umbilical
cord area is important. Keeping this area clean and
dry may reduce infection.
GALE ENCYCLOPEDIA OF MEDICINE

Antigen—A substance, usually a protein, that
causes the formation of an antibody and reacts
specifically with that antibody.
Anti-motility medications—Medications such as
loperamide (Imodium), dephenoxylate (Lomotil),
or medications containing Codeine or narcotics
which decrease the ability of the intestine to contract. This can worsen the condition of a patient
with dysentery or colitis.
Colitis—Inflammation of the colon or large intestine, usually causing diarrhea that may be bloody.
Food irradiation methods—A process using radiant
energy to kill microogranisms in food, to extend the
amount of time in which food can be sold and eaten
safely.
Oral Rehydration Solution (ORS)—A liquid preparation developed by the World Health
Organization that can decrease fluid loss in persons
with diarrhea. Originally developed to be prepared
with materials available in the home, commercial
preparations have recently come into use.
Urea—Chemical formed during the body’s metabolism of nitrogen and normally excreted by the
kidney. Urea levels rise in the blood when kidney
failure occurs.

Resources
BOOKS

Shanson, D. C. Microbiology in Clinical Practice. Woburn:
Butterworth-Heinemann, 1999.
PERIODICALS

Chart, H., M. Sussman, and D. E. S. Stewart-Tull, eds.
‘‘E. coli-Friend or Foe?’’ Journal of Applied
Microbiology TheSociety for Applied Microbiology
Symposium Series No. 29.
Long K., E. Vasquez-Garibay, J. Mathewson, J. de la
Cabada, and H. DuPont. ‘‘The Impact of Infant
Feeding Patterns on Infection and Diarrheal Disease
Due to Enterotoxigenic Escherichia coli.’’ Salud Publica
Mex July–August1999: 263-70.
OTHER

Centers for Disease Control and Prevention. ‘‘Preventing
Foodborne Illness: Escherichia coli 0157:H7.’’ August 9,
1996. [cited May 30, 2004]. <http://www.cdc.gov/
ncidod/dbmd/diseaseinfo/escherichiacoli_g.htm>.

Jill Granger, MS
David Kaminstein, MD
GALE ENCYCLOPEDIA OF MEDICINE

Esophageal acidity test see Esophageal function tests
Esophageal aperistalsis see Achalasia

Esophageal atresia
Definition
Esophageal atresia is a serious birth defect in
which the esophagus, the long tube that connects the
mouth to the stomach, is segmented and closed off at
any point. This condition usually occurs with tracheoesophageal fistula, a condition in which the esophagus is improperly attached to the trachea, the
nearby tube that connects the nasal area to the lungs.
Esophageal atresia occurs in approximately 1 in 4,000
live births.

Description
Failure of an unborn child (fetus) to develop
properly results in birth defects. Many of these defects
involve organs that do not function, or function only
incidentally, before birth, and, as a result, go undetected until the baby is born. In this case, the digestive
tract is unnecessary for fetal growth, since all nutrition
comes from the mother through the placenta and
umbilical cord.
During fetal development, the esophagus and the
trachea arise from the same original tissue. Normally,
the two tubes would form separately (differentiate);
however, in cases of esphageal atresia and tracheoesophageal fistulas, they do not, resulting in various malformed configurations. The most common
configuration is the ‘‘C’’ type, in which the upper
part of the esophagus abruptly ends in a blind pouch,
while the lower part attaches itself to the trachea. This
configuration occurs in 85–90% of cases. Esophageal
atresia without involvement of the trachea occurs in
only 8% of cases.

Causes and symptoms
The cause of esophageal atresia, like that of most
birth defects, is unknown.
An infant born with this defect will at first appear
all right, swallowing normally. However, the blind
pouch will begin to fill with mucus and saliva that
would normally pass through the esophagus to the
stomach. These secretions back up into the mouth
1379

Esophageal atresia

KEY TERMS

Esophageal cancer

Resources

KEY TERMS
Fetal—Refers to the fetus, also known in the first
two months after conception as an embryo.
Fistula—Unnatural connection between two hollow organs or one organ and the outside.

BOOKS

Long, John D., and Roy Orlando. ‘‘Anatomy and
Development and Acquired Anomalies of the
Esophagus.’’ In Sleisenger & Fordtran’s Gastrointestinal
and Liver Disease, edited by Mark Feldman, et al.
Philadelphia: W. B. Saunders Co., 1998.

J. Ricker Polsdorfer, MD
and nasal area, causing the baby to drool excessively.
When fed, the baby will also immediately regurgitate
what he or she has eaten. Choking and coughing
may also occur as the baby breaths in the fluid backing
up from the esophagus. Aspiration pneumonia, an
infection of the respiratory system caused by inhalation of the contents of the digestive tract, may also
develop.

Diagnosis
Physicians who suspect esophageal atresia after
being presented with the above symptoms diagnose
the condition using x-ray imaging or by passing a
catheter through the nose and into the esophagus.
Esophageal atresia is indicated if the catheter hits an
obstruction 4–5 in (10–13 cm) from the nostrils.

Treatment
Infants with esophageal atresia are unlikely to
survive without surgery to reconnect the esophagus.
The procedure is done as soon as possible; however,
prematurity, the presence of other birth defects, or
complications of apiration pneumonia may delay surgery. Once diagnosed, the baby will be fed intraveneously until he or she has recovered sufficiently
from the operation. Mucus and saliva will also be
continuously removed via a catheter until recovery
has occured. When surgery is performed, the esophagus is reconnected and, if neccessary, separated from
the trachea. If the two ends of the esophagus are too
far apart to be reattached, tissue from the large intestine is used to join them.

Prognosis
Surgery to correct esophageal atresia is usually
successful. Post-operative complications may include
difficulty swallowing, since the esophagus may not
contract efficiently, and gastrointestinal reflux,
in which the acidic contents of stomach back up
into the lower part of the esophagus, possibly
causing ulcers.
1380

Esophageal cancer
Definition
Esophageal cancer is a malignancy that develops
in tissues of the hollow, muscular canal (esophagus)
along which food and liquid travel from the throat to
the stomach.

Description
Esophageal cancer usually originates in the inner
layers of the lining of the esophagus and grows outward. In time, the tumor can obstruct the passage of
food and liquid, making swallowing painful and difficult. Since most patients are not diagnosed until the
late stages of the disease, esophageal cancer is associated with poor quality of life and low survival rates.
Squamous cell carcinoma is the most common
type of esophageal cancer, accounting for 95% of all
esophageal cancers worldwide. The esophagus is normally lined with thin, flat squamous cells that resemble
tiny roof shingles. Squamous cell carcinoma can
develop at any point along the esophagus but is most
common in the middle portion.
Adenocarcinoma has surpassed squamous cell
carcinoma as the most common type of esophageal
cancer in the United States. Adenocarcinoma originates in glandular tissue not normally present in the
lining of the esophagus. Before adenocarcinoma can
develop, glandular cells must replace a section of squamous cells. This occurs in Barrett’s esophagus, a precancerous condition in which chronic acid reflux from
the stomach stimulates a transformation in cell type in
the lower portion of the esophagus.
A very small fraction of esophageal cancers are
melanomas, sarcomas, or lymphomas.
There is great variability in the incidence of esophageal cancer with regard to geography, ethnicity,
and gender. The overall incidence is increasing.
GALE ENCYCLOPEDIA OF MEDICINE

Squamous cell carcinoma usually occurs in the
sixth or seventh decade of life, with a greater incidence
in African-Americans than in others. Adenocarcinoma
develops earlier and is much more common in white
patients. In general, esophageal cancer occurs more
frequently in men than in women.



Caustic injury to the esophagus inflicted by swallowing lye or other substances that damage esophageal
cells can lead to the development of squamous cell
esophageal cancer in later life.



Achalasia is a condition in which the lower esophageal sphincter (muscle) cannot relax enough to let
food pass into the stomach. Squamous cell esophageal cancer develops in about 6% of patients with
achalasia.



Tylosis is a rare inherited disease characterized by
excess skin on the palms and soles. Affected patients
have a much higher probability of developing esophageal cancer than the general population. They
should have regular screenings to detect the disease
in its early, most curable stages.



Esophageal webs, which are protrusions of tissue
into the esophagus, and diverticula, which are outpouchings of the wall of the esophagus, are associated with a higher incidence of esophageal cancer.

Causes and symptoms
The exact cause of esophageal cancer is unknown,
although many investigators believe that chronic irritation of the esophagus is a major culprit. Most of the
identified risk factors represent a form of chronic
irritation. However, the wide variance in the distribution of esophageal cancer among different demographic groups raises the possibility that genetic
factors also play a role.
Several risk factors are associated with esophageal
cancer.


Tobacco and alcohol consumption are the major risk
factors, especially for squamous cell carcinoma.
Smoking and alcohol abuse each increase the risk of
squamous cell carcinoma by five-fold. The effects of
the two are synergistic, in that the combination of
smoking and alchohol increases the risk by 25- to
100- fold. It is estimated that drinking about 13
ounces of alcohol every day for an extended period
of time raises the risk of developing esophageal cancer by 18%. That likelihood increases to 44% in
individuals who also smoke one or two packs of
cigarettes a day. Smokeless tobacco also increases
the risk for esophageal cancer.



Gastroesophageal reflux is a condition in which acid
from the stomach refluxes backwards into the lower
portion of the esophagus, sometimes causing symptoms of heartburn. In some cases of gastroesophageal
reflux, the chronic exposure to acid causes the inner
lining of the lower esophagus to change from squamous cells to glandular cells. This is called Barrett’s
esophagus. Patients with Barrett’s esophagus are
roughly 30 to 40 times more likely than the general
population to develop adenocarcinoma of the
esophagus.



A diet low in fruits, vegetables, zinc, riboflavin, and
other vitamins can increase risk of developing to
esophageal cancer.

GALE ENCYCLOPEDIA OF MEDICINE

Symptoms
Unfortunately, symptoms generally don’t appear
until the tumor has grown so large that the patient
cannot be cured. Dysphagia (trouble swallowing or a
sensation of having food stuck in the throat or chest) is
the most common symptom. Swallowing problems
may occur occasionally at first, and patients often
react by eating more slowly and chewing their food
more carefully and, as the tumor grows, switching to
soft foods or a liquid diet. Without treatment, the
tumor will eventually prevent even liquid from passing
into the stomach. A sensation of burning or slight midchest pressure is a rare, often-disregarded symptom of
esophageal cancer. Painful swallowing is usually a
symptom of a large tumor obstructing the opening of
the esophagus. It can lead to regurgitation of food,
weight loss, physical wasting, and malnutrition.
Anyone who has trouble swallowing, loses a significant amount of weight without dieting, or cannot eat
solid food because it is too painful to swallow should
see a doctor.

Diagnosis
A barium swallow is usually the first test performed on a patient whose symptoms suggest esophageal cancer. After the patient swallows a small amount
of barium, a series of x rays can highlight any bumps
or flat raised areas on the normally smooth surface of
the esophageal wall. It can also detect large, irregular
areas that narrow the esophagus in patients with
advanced cancer, but it cannot provide information
1381

Esophageal cancer

About 13,000 new cases of esophageal cancer are
diagnosed in the United States each year. During the
same 12-month period, 12,000 people die of this disease. It strikes between five and ten North Americans
per 100,000. In some areas of China the cancer is
endemic.

Esophageal cancer

esophagus. In Stage IIB, cancer has spread to lymph
nodes near the esophagus and may have invaded deeper layers of esophageal tissue. Stage III esophageal
cancer has spread to tissues or lymph nodes near the
esophagus or to the trachea (windpipe) or other
organs near the esophagus. Stage IV cancer has spread
to distant organs like the liver, bones, and brain.
Recurrent esophageal cancer is disease that develops
in the esophagus or another part of the body after
initial treatment.
Surgery
A close-up view of a cancerous esophageal tumor. (Custom
Medical Stock Photo. Reproduced by permission.)

about disease that has spread beyond the esophagus.
A double contrast study is a barium swallow with air
blown into the esophagus to improve the way the
barium coats the esophageal lining. Endoscopy is a
diagnostic procedure in which a thin lighted tube
(endoscope) is passed through the mouth, down the
throat, and into the esophagus. Cells that appear
abnormal are removed for biopsy. Once a diagnosis
of esophageal cancer has been confirmed through
biopsy, staging tests are performed to determine
whether the disease has spread (metastasized) to tissues or organs near the original tumor or in other parts
of the body. These tests may include computed tomography, endoscopic ultrasound, thoracoscopy, laparoscopy, and positron emission tomography.

The most common operations for the treatment
of esophageal cancer are esophagectomy and esophagogastrectomy. Esophagectomy is the removal
of the cancerous part of the esophagus and nearby
lymph nodes. This procedure is performed only on
patients with very early cancer that has not spread to
the stomach. Esophagogastrectomy is the removal of
the cancerous part of the esophagus, nearby lymph
nodes, and the upper part of the stomach. The
resected esophagus is replaced with the stomach or
parts of intestine so the patient can swallow. These
procedures can significantly relieve symptoms and
improve the nutritional status of more than 80% of
patients with dysphagia. Although surgery can cure
some patients whose disease has not spread beyond
the esophagus, but more than 75% of esophageal
cancers have spread to other organs before being
diagnosed. Less extensive surgical procedures can
be used for palliation.
Chemotherapy

Treatment
Treatment for esophageal cancer is determined by
the stage of the disease and the patient’s general
health. The most important distinction to make is
whether the cancer is curable. If the cancer is in the
early stages, cure may be possible. If the cancer is
advanced or if the patient will not tolerate major
surgery, treatment is usually directed at palliation
(relief of symptoms only) instead of cure.
Staging
Stage 0 is the earliest stage of the disease. Cancer
cells are confined to the innermost lining of the esophagus. Stage I esophageal cancer has spread slightly
deeper, but still has not extended to nearby tissues,
lymph nodes, or other organs. In Stage IIA, cancer has
invaded the thick, muscular layer of the esophagus
that propels food into the stomach and may involve
connective tissue covering the outside of the
1382

Oral or intravenous chemotherapy alone will
not cure esophageal cancer, but pre-operative treatments can shrink tumors and increase the probability that cancer can be surgically eradicated.
Palliative chemotherapy can relieve symptoms of
advanced cancer but will not alter the outcome of
the disease.
Radiation
External beam or internal radiation, delivered by
machine or implanted near cancer cells inside the
body, is only rarely used as the primary form of treatment. Post-operative radiation is sometimes used to
kill cancer cells that couldn’t be surgically removed.
Palliative radiation is effective in relieving dysphagia
in patients who cannot be cured. However, radiation is
most useful when combined with chemotherapy as
either the definitive treatment or preoperative
treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Computed tomography—A radiology test by
which images of cross-sectional planes of the
body are obtained.
Endoscopic ultrasound—A radiology test utilizing
high frequency sound waves, conducted via an
endoscope.
Laparoscopy—Examination of the contents of the
abdomen through a thin, lighted tube passed
through a small incision.
Positron emission tomography—A radiology test
by which images of cross-sectional planes of the
body are obtained, utilizing the properties of the
positron. The positron is a subatomic particle of
equal mass to the electron, but of opposite charge.
Synergistic—The combined action of two or more
processes is greater than the sum of each acting
separately.
Thoracoscopy—Examination of the contents of the
chest through a thin, lighted tube passed through a
small incision.

Palliation
In addition to surgery, chemotherapy, and radiation, other palliative measures can provide symptomatic relief. Dilatation of the narrowed portion of
the esophagus with soft tubes can provide short-term
relief of dysphagia. Placement of a flexible, selfexpanding stent within the narrowed portion is also
useful in allowing more food intake.
Follow-up treatments

an endoscope. It can improve dysphagia, but multiple
treatments are required, and the benefit is seldom
long-lasting.

Prognosis
Since most patients are diagnosed when the cancer
has spread to lymph nodes or other structures, the
prognosis for esophageal cancer is poor. Generally,
no more than half of all patients are candidates for
curative treatment. Even if cure is attempted, the cancer can recur.

Prevention
There is no known way to prevent esophageal
cancer.
Resources
BOOKS

Heitmiller, Richard F., Arlene A. Forastiere, and Lawrence
R.Kleinberg. ‘‘Esophagus.’’ In Clinical Oncology,
edited by Martin D. Abeloff, 2nd ed. New York:
Churchill Livingstone, 2000.
Zwischenberger, Joseph B., Scott K. Alpard, and Mark
B.Orringer. ‘‘Esophageal Cancer.’’ In Sabiston
Textbook of Surgery, edited by Courtney Townsend,
Jr., 16th ed. Philadelphia: W. B. Saunders Company,
2001.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800)ACS-2345. <http://
www.cancer.org>.
National Coalition for Cancer Survivorship. 1010 Wayne
Avenue, 5th Floor, Suite 300, Silver Spring, MD 20910.
Telephone: 1-888-650-9127.

Maureen Haggerty
Kevin O. Hwang, M.D.

Regular barium swallows and other imaging studies are necessary to detect recurrence or spread of
disease or new tumor development.

Alternative treatment
Photodynamic therapy (PDT) involves intravenously injecting a drug that is absorbed by cancer
cells and kills them after they are exposed to specific laser beams. PDT can be used for palliation,
but it also cured some early esophageal cancers
during preliminary studies. Researchers are comparing its benefits with those of more established
therapies.
Endoscopic laser therapy involves delivering
short, powerful laser treatments to the tumor through
GALE ENCYCLOPEDIA OF MEDICINE

Esophageal disorders
Definition
The esophagus is a tube that connects the back of
the mouth to the stomach. Abnormalities of the esophagus generally fall into one of four categories: structural abnormalities, motility disorders, inflammatory
disorders, and malignancies.
1383

Esophageal disorders

KEY TERMS

Esophageal disorders

Description
The main function of the esophagus is to move
food from the back of the mouth to the stomach. The
adult esophagus is about 10 in (25 cm) long. It is
consists of a layer of cells that secretes mucus and two
layers of muscle, one circular and one longitudinal.
This combination of muscles allows the esophagus to
contract and propel food from the mouth the stomach.
This rhythmic contraction is called peristalsis. At the
end of the esophagus nearest the mouth is a ring of
muscle called the upper esophageal sphincter (UES). A
similar muscular ring called the lower esophageal
sphincter (LES) is found 1–1.5 in (2–4 cm) above the
point where the esophagus enters the stomach. The
LES contracts to prevent the contents of the stomach
from backflowing into the lower end of the esophagus.
Structural abnormalities
Structural abnormalities of the esophagus can be
either congenital or acquired. Congenital abnormalities occur in about 1 of every 3,000–5,000 births. The
two most common congenital esophageal abnormalities are esophageal atresia (EA) and tracheoesophageal fistula (TEF).
EA is a condition in which the esophagus is interrupted and the portion of the tube near the mouth is
not connected to the portion that goes into the stomach. Usually the upper part of the tube ends in a
blind pouch. This creates a life-threatening condition
for the newborn who is unable to eat.
TEF is a condition in which the esophagus is
connected to the trachea (windpipe). The trachea and
the esophagus lie parallel to each other in the neck.
Sometimes during fetal development, a connection
called a fistula develops between these two tubes.
This allows food to enter the trachea and be inhaled
into the lungs causing a life-threatening condition
called aspiration pneumonia. Often TEF and EA are
present in the same infant. Both these conditions must
be surgically corrected for the infant to survive.
Other, less common congenital structural
abnormalities include webs, stenosis, cysts, and diverticula. Webs are thin membranes that lie across the
esophagus and cause a partial obstruction. Stenosis is
the abnormal reduction in the diameter of the esophagus due to thickening of the esophageal wall
Diverticula are pouches of tissue that extend off the
esophagus. Both diverticula and stenosis can be either
congenital or acquired later in life.
Acquired structural abnormalities of the esophagus include Schatzki ring and hiatal hernia. Schatzki
1384

ring, sometimes called a lower esophageal ring, is a
circular band of tissue located where the esophagus
empties into the stomach. This ring is found in 6–14%
of individuals, and for most people the presence of this
ring does not create symptoms. Schatzki ring is found
equally in all races and in both men and women.
Schatzki rings that cause symptoms usually occur in
middle age individuals. The ring can cause intermittent problems swallowing food or food impaction
where the esophagus enters the stomach.
The esophagus passes a gap in the diaphragm
called the diaphragmatic hiatus in order to reach the
stomach. Hiatal hernia (also called hiatus hernia) is a
condition that occurs when a portion of the stomach
pushes up through this gap next to the esophagus.
Although a hiatus hernia is not a direct structural
abnormality of the esophagus, it is associated with
gastroesophageal reflux disease (GERD) or heartburn
in which the acidic stomach contents backflow into the
lower part of the esophagus and erode the cell lining.
Hiatal hernia is very common and often causes no
symptoms. It is treated as a separate entry.
Lacerations, tears and ruptures of the esophagus,
known as Mallory-Weiss syndrome and Boerhaave
syndrome, are life-threatening disorders. MalloryWeiss syndrome usually occurs in alcoholics. In both
conditions, tears result from vomiting and retching.
The resulting bleeding creates a medical emergency
that can be fatal.
Motility abnormalities
Motility abnormalities create difficulty in swallowing, called dysphagia. Dysphagia is a symptom of
several esophageal motility disorders as well as several
obstructive disorders such as esophageal webs or
Schatzki ring.
Achalasia is an esophageal motility disorder
caused by uncoordinated contractions of the two muscular layers that make up the esophagus. Because
muscular contractions are disorganized, peristalsis
and the orderly movement of food down the esophagus does not occur. In addition, with achalasia the
lower esophageal sphincter remains contracted when
food is present in the esophagus which prevents the
food from entering the stomach. This causes the esophagus to bulge above the LES, a condition called
megaesophagus.
Achalasia is caused by destruction of some of the
nerve cells that control muscular contraction of the
esophagus. This disorder generally begins in young
adults and becomes progressively worse as the individual ages. Individuals with achalasia also have a
GALE ENCYCLOPEDIA OF MEDICINE

Individuals can also develop esophageal motility
disorders secondary to other muscle diseases.
Scleroderma is a disorder in which smooth muscle
begins to atrophy. The smooth muscle in the esophagus can be affected just like other smooth muscle in the
body, making swallowing difficult. Scleroderma esophagus is also associated with GERD and increased
risk of cancer of the esophagus. Other conditions such
as diabetes mellitus, alcoholism, and some psychiatric
disorders can also produce secondary esophageal
motility disorders.
Inflammatory disorders
Inflammatory esophageal disorders fall under the
general name of esophagitis. Esophagitis causes the
esophagus to become swollen and the lining of
the esophagus becomes eroded and sore. It is present
in about 5% of the population in the United States.
There are four main types of esophagitis: reflux, infection, corrosive, and radiation. Reflux esophagitis is
caused by GERD when the lower esophageal sphincter does not close tightly and the acidic contents of the
stomach enter esophagus. GERD is common and is
treated in depth in a separate entry. Infectious esophagitis can be caused fungal, viral, or bacterial infections.
Infectious esophagitis occurs frequently in individuals
with compromised immune systems, such as those
with AIDS or leukemia. Corrosive esophagitis occurs
when an individual either intentionally or accidentally
swallows harsh chemicals such as lye. Radiation esophagitis is a complication of radiation treatments for
cancer of the esophagus or lung.
Malignancies
Barrett’s esophagus is a pre-cancerous condition
which has a high risk of developing into esophageal
cancer. It is found most commonly in white males in
their 50s and 60s and is usually associated with years
of chronic GERD.
Cancers of the esophagus tend to be aggressive
and have poor outcomes. Adenocarcinoma is the primary cancer of the esophagus. Esophageal cancers are
treated in detail in a separate entry.

Causes and symptoms
The causes of esophageal disorders depend on the
type of disorder. Congenital defects are caused by
errors in development. It is not clear why some structural disorders, such as Schatzki ring and hiatal
GALE ENCYCLOPEDIA OF MEDICINE

hernia, occur. Many more people have these defects
than develop symptoms or seek medical care, so that
the presence of these asymptomatic structural defects
is found only during autopsies. Other individuals
develop symptoms that require medical attention.
Obesity and advancing age are thought to be contributing factors in developing symptoms.
Achalasia is caused by death of nerve cells that
control the muscles that make peristalsis possible.
These nerve cells are destroyed by T cells that are
part of the body’s immune system. It is not clear
what triggers these T cells to attack inappropriately.
Difficulty swallowing develops slowly, usually beginning in young adults, although the disorder can occur
in children. As nerve control is lost, the LES fails to
relax, preventing food from entering the stomach. As a
result, the lower part of the esophagus becomes
stretched creating a condition called megaesophagus.
At night, food is often regurgitated and can be inhaled
into the lungs, creating the risk of aspiration pneumonia. Achalasia can also be caused by Chagas’ disease, a
disease rare in North America, but common in Central
and South America. Individuals with achalasia are
also at higher risk to develop esophageal cancer, esophageal infections, and esophageal rupture.
Inflammatory esophagitis is most often caused by
GERD. Infectious esophagitis can be caused by fungi,
usually Candida albicans, bacteria, or viruses. Fungal
infections usually occur in individuals who have diabetes, a weakened immune system, or who are taking
antibiotics. Antibiotics change the balance of naturally
occurring bacteria in the esophagus and allow fungi,
which are normally present in the digestive tract, to
grow unchecked. The most common causes of viral
esophagitis are cytomegalovirus (CMV) and Herpes
simplex. These are usually opportunistic infections in
individuals with HIV/AIDS.
Corrosive esophagitis is usually caused by swallowing harsh chemicals, but it can also be caused by
certain medications. Radiation esophagus is a side
effect of radiation therapy for cancer.

Diagnosis
EA and TEF can sometimes be diagnosed in fetal
ultrasounds before birth. If not, these defects become
obvious soon after birth, because the infant is unable
to eat. The inability to pass a tube from the mouth to
the stomach is a definite diagnosis for EA. TEF can be
detected through x-rays.
A barium swallow x ray with video is the basic
method of diagnosing most esophageal disorders. For
1385

Esophageal disorders

higher risk of developing esophageal cancer at an earlier than usual age.

Esophageal disorders

a barium swallow x ray, the individual drinks a barium, a material that coats the esophagus and shows up
on x-ray film. A video camera records the passage of
the barium down the esophagus in order to detect
swallowing disorders or pockets and pouches (diverticula) bulging from the esophagus. A barium swallow
is also used to detect Schatzki rings.
Upper gastrointestinal endoscopy is often used in
conjunction with a barium swallow to diagnose esophageal disorders. In an endoscopy, a thin, fiberoptic
tube with a tiny camera is inserted into the esophagus.
This allows the physician to see the lining of the esophagus. Endoscopes are equipped to take samples
(biopsies) of any areas that may appear pre-cancerous
or cancerous or to collect samples to test for the
organism causing infectious esophagitis.
GERD can often be diagnosed from symptoms
such as heartburn and regurgitation. Mallory-Weiss
tears and Boerhaave syndrome are difficult to diagnose. Individuals with these disorders are often
severely ill and have intense chest pain and vomiting,
however chest x rays are normal 10–15% of the
time. CT scans may be used in conjunction with
chest x rays.

Treatment
Surgery is the only treatment for EA and TEF. It
is done as soon as possible, based on the condition of
the infant and any other birth defects that may be
present that could affect the surgery.
Schatzki rings and hiatal hernias often cause no or
mild symptoms and need no treatment. In severe cases,
Schatzki rings are treated with bougienage. In this
treatment, a series of tubes of ever-increasing diameter
are inserted through the esophagus to stretch the ring.
Stretching can also be done with balloon dilation.
Surgery is done when no other treatment succeeds in
relieving symptoms. Large hiatal hernias can be
repaired surgically, but often there is not need for
treatment. GERD accompanies many hiatal hernias.
GERD can be treated with drugs to block acid production in the stomach (H2 blockers or proton pump
inhibitors) and changes in diet. In severe cases of
GERD stomach surgery may be necessary.
Mallory-Weiss syndrome and Boerhaave syndrome are medical emergencies. The individual is
stabilized and the tear or rupture is repaired surgically.
The chance of infection (sepsis) is high, so individuals
are admitted to intensive care and do not take
any food or liquid by mouth for 7–10 days. Hospital
stays can last months, and repeated tears are possible.
1386

Achalasia is treated with drugs that relax the
smooth muscle and allow the LES to relax and open.
When this fails, surgery to may be needed. Individuals
that are not good candidates for surgery (the elderly or
frail) may be treated by injecting botulinum toxin
(botox) into the LES to prevent it from closing. The
disadvantage of this treatment is its expense and the
fact that more than one injection is needed.
Infectious esophagitis is treated by treating the
underlying cause of the disease with antifungal, antiviral or antibiotic medications. These can be given
either by mouth or intravenously (IV) depending on
the severity of the disease.
Malignancies are treated with chemotherapy and
radiation. See the entry on esophageal cancer for specific details.

Prognosis
The outcome of treatment depends on the type of
disorder, severity, age, and general health of the individual. EA and TEF surgeries are often successful, but
infants born with these conditions frequently have
other congenital abnormalities that compromise their
health.
When needed, treatment for Schatzki rings produces relief of symptoms, but almost always has to be
repeated periodically.
Mallory-Weiss and Boerhaave syndromes are
often fatal. Thirty to fifty percent of individuals die
from these disorders even if they are diagnosed
promptly. If diagnosis is delayed, the death rate can
be as high as 90%.
Achalasia and scleroderma esophagus are progressive diseases that need continued therapy. They
frequently lead to serious weight loss and malnutrition.
The outcome for treatment of inflammatory esophagitis depends almost entirely on the success of
treating the underlying cause. Where individuals
have a weakened immune system, infectious esophagitis can be an ongoing problem. When inflammatory
esophagitis is caused by GERD, treatment along with
lifestyle modification is usually successful in providing
relief.
Esophageal cancers are aggressive and have generally poor outcomes.

Prevention
Many symptoms of esophageal disorders can be
prevented or alleviated by lifestyle changes that
include:
GALE ENCYCLOPEDIA OF MEDICINE

Vossough, Arastoo and Stephen E. Rubesin. Schatzki Ring,
14 April 2003 [cited 1 March 2005]. <http://
www.emedicine.com/radio/topic620.htm>.

Atrophy—To wither and become unresponsive.
Congenital—Present at birth.
Diaphragm—A muscle that separates the cavity
containing the lungs from the abdomen.
Diverticula—Abnormal pouches of tissue that
bulge off the main part of the digestive system.

Tish Davidson, A.M.

Esophageal diverticula see Esophageal
pouches

Peristalsis—A wave of contractions passing
through a hollow muscular tube such as the
esophagus or intestine.

Esophageal function tests
Definition



weight loss to control obesity



eating slowly and chewing food well



eating smaller and more frequent meals



not eating several hours before going to bed



limiting the use of alcohol and caffeine

The esophagus is the swallowing tube through
which food passes on its way from the mouth to the
stomach. The main function of this organ is to propel
food down into the stomach. There is also a mechanism to prevent food from coming back up or ‘‘refluxing’’ from the stomach into the esophagus.
Esophageal function tests are used to determine if
these processes are normal or abnormal.

Resources

Purpose

OTHER

Ansari, Sajid and Sandeep Mukherjee. Esophagitis, 22
November 2004 [cited 1 March 2005]. <http://www.
emedicine.com/med/topic735.htm>.
Carey, Martin J. Esophageal Perforation, Rupture
and Tears, 26 July 2002 [cited 1 March 2005].
<http://www.emedicine.com/emerg/
topic176.htm>.
‘‘Esophageal Disorders.’’ The Merck Manual. Eds. Mark
H. Beers and Robert Berkow. 1995-2005 [cited 1
March 2005]. <http://www.merck.com/mrkshared/
mmanual/section3/chapter20/20a.jsp>.
Fayyad, Abdullah and Eric Gaumnitz. Esophageal
Motility Disorders, 3 September 2004 [cited 1 March
2005]. <http://www.emedicine.com/med/
topic740.htm>.
Minkes, Robert K. and Alison Snyder. Congenital
Anomalies of the Esophagus, 14 June 2004 [cited 1
March 2005]. <http://www.emedicine.com/ped/
topic2934.htm>.
Paik, Nam-Jong. Dysphagia, 19 August 2004 [cited 1 March
2005]. <http://www.emedicine.com/pmr/
topic194.htm>.
Patti, Marco. Gastroesophageal Reflux Disease, 29
December 2004 [cited 1 March 2005]. <http://www.
emedicine.com/med/topic857.htm>.
Qureshi, Wagar A. Hiatal Hernia, 29 December 2004 [cited 1
March 2005]. <http://www.emedicine.com/pmr/
topic1012.htm>.

GALE ENCYCLOPEDIA OF MEDICINE

The esophagus is a long, muscular tube that also
has two muscles (or sphincters) at the top and bottom.
All of these muscular areas must contract in an exact
sequence for swallowing to proceed normally. There
are three main symptoms that occur when esophageal
function is abnormal: difficulty with swallowing (dysphagia), heartburn, and chest pain.
Doctors perform a variety of tests to evaluate
these symptoms. Endoscopy, which is not a test of
esophageal function, is often used to determine if the
lining of the esophagus has any ulcers, tumors, or
areas of narrowing (strictures). Many times, however,
endoscopy only shows the doctor if there is injury to
the esophageal lining, and the procedure gives no
information about the cause of the problem.
Therefore, in addition to endoscopy, several studies are available that measure esophageal function.
There are three basic types of tests used to assess
esophageal function:


Manometry is used to study the way the muscles of
the esophagus contract, and is most useful for the
investigation of difficulty with swallowing.



Esophageal pH monitoring measures changes in esophageal acidity, and is valuable for evaluating
patients with heartburn or gastroesophageal reflux
disease (GERD).
1387

Esophageal function tests

KEY TERMS

Esophageal function tests



X-ray studies investigate swallowing difficulties.
They either follow the progress of barium during
swallowing using a fluoroscope, or they use radioactive scanning techniques.

Precautions
Pregnant patients undergoing x-ray exams should
carefully review the risks and benefits with their doctors. Most x-ray exams of the gastrointestinal tract do
not involve radiation levels that are harmful to the
unborn baby.

Description
Manometry
This study is designed to measure the pressure
changes produced by contraction of the muscular portions of the esophagus. An abnormality in the function
of any one of the segments of the swallowing tube
causes difficulty in swallowing. Doctors call this symptom dysphagia. This exam is most useful in evaluating
those patients whose endoscopy is negative.
During manometry, the patient swallows a thin
tube carrying a device that senses changes in pressures
in the esophagus. Readings are taken at rest and during swallowing. Medications are sometimes given during the study to help in the diagnosis. The results are
then transmitted to recording equipment. Manometry
can best identify diseases that produce disturbances of
motility or contractions of the esophagus.
ESOPHAGEAL PH MONITORING. This procedure
involves measuring the esophagus’ exposure to acid
that has ‘‘refluxed’’ from the stomach. The test is ideal
for evaluating recurring heartburn or GERD. Too
much acid produces not only heartburn, but also
ulcers that can bleed or produce areas of narrowing
(strictures) when they heal.

Normally, acid refluxes into the esophagus in only
small amounts for short periods of time. A muscle
called the lower esophageal sphincter prevents excessive reflux. Spontaneous contractions that increase
esophageal emptying and production of saliva are
other important protective mechanisms.
‘‘pH’’ is the scientific term that tells just how acidic
or alkaline a substance is. Researchers have shown that
in the esophagus, the presence of acid is damaging only
if it persists for prolonged periods. Therefore, the test
has been designed to monitor the level of acidity over
24 hours, usually in the home. In this way, patients
maintain their daily routine, documenting their symptoms, and at what point in their activities they
1388

occurred. During this period, a thin tube with a pH
monitor remains in the esophagus to record changes.
After the study, a computer is used to compare changes
in acidity with symptoms reported by the patient.
Surgery is an effective and long-lasting treatment
for symptoms of recurrent reflux and is the choice of
many patients and doctors. pH monitoring is usually
performed before surgery to confirm the diagnosis and
to judge the effects of drug therapy.
X-RAY TESTS. These fall into two categories: (1)
those done with the use of barium and a fluoroscope;
and (2) those performed with radioactive materials.

Studies performed with fluoroscopy are of greatest value in identifying a structural abnormality of the
esophagus. Although this is not truly an esophageal
function test, it does allow doctors to consider other
diagnostic possibilities. Often a sandwich or marshmallow coated with barium is used to identify the site
of an obstruction.
During fluoroscopy, the radiologist can observe
the passage of material through the esophagus in real
time, and video recordings can also be done. This is
particularly useful when the swallowing symptoms
appear to involve mainly the upper region of the esophagus. The most common cause of swallowing difficulties is a previous stroke, although other diseases of
the neuromuscular system (like myasthenia gravis) can
produce the same symptoms.
Scans using low-dose radioactive materials are useful because they are able not only to demonstrate that
food passes through the esophagus more slowly than
normal, but also how slow. These studies involve swallowing food coated with material that is followed by a
nuclear medicine scanner. Scans are best used when
other methods have failed to make a diagnosis, or if it
is necessary to determine the degree of the abnormality.
As of 1997, scans mainly served as research tools.

Preparation
Patients should not eat or drink for several hours
before the exam. Many medications affect the esophagus; doses sometimes need to be adjusted or even
stopped for a while. Patients must inform doctors of
all medications taken, including over-the-counter
medications (purchased without a doctor’s prescription), and any known allergies.

Aftercare
For most of these studies, no special care is needed
after the procedure. Patients can often go about
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Exposure of a fetus to x rays, especially in the first
three months, is a potential risk.
Other studies of esophageal function are essentially
free of any significant risk. The tubes passed during
these procedures are small, and most patients adjust to
them quite well. However, since medications cannot be
used to relax patients, some may not tolerate the exam.

Abnormal results
Manometry is used to diagnose abnormalities
related to contraction or relaxation of the various
muscular regions of the esophagus. These studies cannot distinguish whether injury to either the muscle or
nerves of the esophagus is producing the abnormal
results. Only the final effect on esophageal muscle is
identified. Results should be interpreted in light of the
patient’s entire medical history.
For example, there are many diseases that cause
poor relaxation of the lower esophageal sphincter.
When no cause is found, the disease is called achalasia.
Abnormal results of pH tests can confirm symptoms of heartburn or indicate a cause of chest pain
(or rarely, swallowing difficulties). Doctors may want
to start or change medications based on these results,
or even repeat the test using different doses of medication. As noted above, these studies are indicated
before surgical treatment of GERD.
X-ray tests can only serve to document an
abnormality, and they are far from perfect. If they
are negative, then other studies are often needed.
Resources
PERIODICALS

Mittal, Ravinder K., and David H. Balaban. ‘‘The
Esophagogastric Junction.’’ New England Journal of
Medicine 336 (27 Mar. 1997): 924-932.

David Kaminstein, MD

Esophageal laceration see Mallory-Weiss
syndrome
Esophageal manometry see Esophageal
function tests
GALE ENCYCLOPEDIA OF MEDICINE

Esophageal pouches
Definition
Esophageal pouches, also known as esophageal
diverticula, are pocket-like structures formed when
the interior space of the esophagus, the tube that connects the mouth to the stomach, protrudes into the
walls that surround it.

Description
The esophagus is a muscular tube that propels
food into the stomach. A defect in the wall of the
esophagus may allow the lining to herniate, creating
a space where food can be caught. Pouches can
appear anywhere between the throat and the stomach. They occur primarily in men and usually
later in life.
Different names for the condition apply to different locations along the esophagus:


Zenker’s diverticula are pharyngeal pouches, or ones
that occur in the upper neck area at the top of the
esophagus.



Traction diverticula are a type of mid-esophageal
pouch.



Epiphrenic diverticula occur at the bottom of the
esophagus near where it enters the stomach.

Causes and symptoms
To propel food into the stomach (or out of it
during vomiting) the esophagus generates internal
pressure just like the bowel. Under certain circumstances, that pressure can herniate the esophageal
lining through a weakness in the wall, creating a
pouch (a balloon squeezed in the hand will herniate
through the fingers in the same way). Pouches are
more common in people who have motility disorders
of the esophagus, swallowing that is not well coordinated and may be spastic. A traction diverticulum can
develop from a scar that pulls the esophagus out of
shape. Food and saliva can collect in all of these
pouches.
Pouches in the neck usually cause bad breath (halitosis) and the regurgitation of swallowed food and
saliva. Some patients with Zenker’s diverticula can
push on their neck and make old food appear in their
mouths. Pouches near the stomach may cause swallowing problems, conditions known as achalasia or
dysphagia. Mid-esophageal pouches usually cause no
symptoms.
1389

Esophageal pouches

normal daily activities following any of these tests.
One exception is for those who undergo an x-ray
exam with the use of barium. This can have a constipating effect and patients should ask about using a
mild laxative later on.

Esophageal pouches
A split x-ray image of the upper chest, neck, and esophagus (left), and chest and esophagus (right). (Custom Medical Stock Photo.
Reproduced by permission.)

Diagnosis

KEY TERMS
Achalasia—Failure of the lower end of the esophagus (or another tubular valve) to open, resulting in
obstruction, either partial or complete.
Contrast agent—A substance that produces shadows on an x ray so that hollow structures can be
more easily seen.
Dysphagia—Difficult swallowing.
Esophagoscopy—Looking down the esophagus
with a flexible viewing instrument.
Herniate—To protrude beyond usual limits.
Manometry—Pressure measurement.

In the most serious cases, a person may be unable
to swallow because the esophagus is obstructed, or the
esphagus may rupture, spilling its contents into the
chest or neck.
1390

Difficulty swallowing, bad breath, or food reappearing in the back of the mouth are among the signs
physicians look for when diagnosing this condition.
Sometimes the patient may also experience pain in the
chest resembling a heart attack. A series of x rays
taken while swallowing a contrast agent usually
demonstrates the diverticulum clearly. An esophagoscopy may also be needed to gather more detail.
Manometry, measuring pressures inside the esophagus using a balloon that is passed down it, may help
determine the cause of the diverticula.

Treatment
Treatment for this condition is primarily aimed at
alleviating symptoms. Physicians direct the patient to
eat a bland diet, to chew his or her food thoroughly,
and to drink water after eating to clean out the pouches.
If the condition is severe, several types of surgery are
available to remove the pouches and repair the defects.
If a pouch is due to a stenosis (narrowing) in the
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The two complications that can render these nuisances dangerous, obstruction and rupture, are emergencies. Both require immediate medical attention.
Other than that, diverticula will usually grow slowly
over the years, gradually increasing the symptoms
they cause.
Resources
BOOKS

Goyal, Raj K. ‘‘Diseases of the Esophagus.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony S.
Fauci, et al. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Esophageal ulcers see Ulcers (digestive)

Esophagogastroduodenoscopy
Definition
An endoscope as used in the field of gastroenterology (the medical study of the stomach and intestines) is a thin, flexible tube that uses a lens or
miniature camera to view various areas of the gastrointestinal tract. When the procedure is limited to the
examination of the inside of the gastrointestinal tract’s
upper portion, it is called upper endoscopy or esphagogastroduodenoscopy (EGD). With the endoscope,
the esophagus (swallowing tube), stomach, and duodenum (first portion of the small intestine) can be
easily examined, and abnormalities frequently treated.
Patients are usually sedated during the exam.

Purpose
EGD is performed to evaluate or treat symptoms
relating to the upper gastrointestinal tract, such as:


upper abdominal or chest pain



nausea or vomiting



difficulty swallowing (dysphagia)



bleeding from the upper intestinal tract



anemia (low blood count). EGD can be used to treat
certain conditions, such as an area of narrowing or
bleeding in the upper gastrointestinal tract

GALE ENCYCLOPEDIA OF MEDICINE

Upper endoscopy is more accurate than x rays for
detecting inflammation, ulcers, or tumors. It is used to
diagnose early cancer and can frequently determine
whether a growth is benign (not cancerous) or malignant (cancerous).
Biopsies (small tissue samples) of inflamed or
‘‘suspicious’’ areas can be obtained and examined by
a pathologist. Cell scrapings can also be taken by the
introduction of a small brush; this helps in the diagnosis of cancer or infections.
When treating conditions in the upper gastrointestinal tract, small instruments are passed through the
endoscope that can stretch narrowed areas (strictures),
or remove swallowed objects (such as coins or pins). In
addition, bleeding from ulcers or vessels can be treated
by a number of endoscopic techniques.
Recent studies have shown the usefulness of endoscopic removal of early tumors of the esophagus or
stomach. This is done either with injection of certain
materials (like alcohol), or with the use of instruments
(like lasers) that burn the tumor. Other techniques
combining medications and lasers also show promise.

Precautions
Patients should inquire as to the doctor’s expertise
with these procedures, especially when therapy is the
main goal. The doctor should be informed of any
allergies, medication use, and medical problems.

Description
First, a ‘‘topical’’ (local) medication to numb the
gag reflex is given either by spray or is gargled.
Patients are usually sedated for the procedure (though
not always) by injection of medications into a vein.
The endoscopist then has the patient swallow the
scope, which is passed through the upper gastrointestinal tract. The lens or camera at the end of the instrument allows the endoscopist to examine each portion
of the upper gastrointestinal tract; photos can be taken
for reference. Air is pumped in through the instrument
to allow proper observation. Biopsies and other procedures can be performed without any significant
discomfort.

Preparation
The upper intestinal tract must be empty for the
procedure, so it is necessary NOT to eat or drink for at
least 6–12 hours before the exam. Patients need to
inquire about taking their medications before the
procedure.
1391

Esophagogastroduodenoscopy

esophagus it may be possible to relieve it by passing a
dilator through it, a process called bougeinage.

Esophagogastroduodenoscopy
Esophagogastroduodenoscopy (EGD) is performed to evaluate or treat symptoms relating to the upper gastrointestinal tract. By
inserting an endoscope into the mouth and guiding it through the gastrointestinal tract, the esophagus, stomach, and
duodenum can be examined and abnormalities treated. (Illustration by Electronic Illustrators Group.)

KEY TERMS
Pathologist—A doctor who specializes in the anatomic (structural) and chemical changes that occur
with diseases. These doctors function in the laboratory, examining biopsy specimens, and regulating
studies performed by the hospital laboratories
(blood tests, urine tests, etc). Pathologists also perform autopsies.

Aftercare
Someone should be available to take the person
home after the procedure and stay with them for a
while; patients will not be able to drive themselves due
to sedation. Pain or any other unusual symptoms
should be reported immediately.
1392

It is important to recognize early signs of any
possible complication. The doctor should be notified
if the patient has fever, trouble swallowing, or increasing throat, chest, or abdominal pain.

Risks
EGD is safe and well tolerated; however, complications can occur as with any procedure. These are most
often due to medications used during the procedure, or are
related to endoscopic therapy. The overall complication
rate of EGD is less than 2%, and many of these complications are minor (such as inflammation of the vein through
which medication is given). However, serious ones can
and do occur, and almost half of them are related to the
heart or lungs. Bleeding or perforations (holes in the
gastrointestinal tract) are also reported, especially when
tumors or narrowed areas are treated or biopsied.
Infections have also been rarely transmitted; improved
cleaning techniques should be able to prevent them.
GALE ENCYCLOPEDIA OF MEDICINE

‘‘hysterical blindness,’’ in which loss of vision is not
due to any nerve damage.

OTHER

‘‘Understanding Upper Endoscopy.’’ American Society for
Gastrointestinal Endoscopy. <http://www.asge.org>.



Auditory evoked potentials are used to diagnose
hearing losses. They can distinguish damage to the
acoustic nerve (which carries signals from the ear to
the brain stem) from damage to the auditory pathways within the brainstem. Most auditory EPs
record activity from the brainstem, and are therefore
called ‘‘brainstem auditory evoked potentials.’’
Disorders diagnosed with auditory EPs include
acoustic neuroma (tumors of the inner ear) and multiple sclerosis (chronic disease in which nerves lose
patches of their outer covering). They may also be
used to assess high frequency hearing ability, to
determine brain death, and to monitor brainstem
function during surgery



Somatosensory evoked potentials record transmission of nerve impulses from the limbs to the brain,
and can be used to diagnose nerve damage or degeneration within the spinal cord or nerve roots from
multiple sclerosis, trauma, or other degenerative disease. Somatosensory EPs can be used to distinguish
central versus peripheral nerve disease, when combined with results from a nerve conduction velocity
test, which measures nerve function in the
extremities.

David Kaminstein, MD

Essential tremor see Tremors
Estradiol see Hormone replacement therapy
Estrogen see Hormone replacement therapy
Estrogen fractions test see Sex hormones tests
Estrogen replacement therapy see Hormone
replacement therapy
Ethambutol see Antituberculosis drugs
Etodolac see Nonsteroidal anti-inflammatory drugs

Evoked potential studies
Definition
Evoked potential studies are a group of tests of the
nervous system that measure electrical signals along
the nerve pathways.

Purpose
Nerves convey information to the body by sending electrical signals down the length of the nerve.
These signals can be recorded by wires placed over
the nerves on the surface of the skin, in a procedure
called an evoked potential (EP) study. The person
conducting the test evokes the patient’s neural activity
by visual or auditory stimulation or using a mild electrical shock. This causes changes in the electrical
potential in the nerves. Analysis of the signals can
provide information about the condition of nerve
pathways, especially those in the brain and spinal
cord. They can indicate the presence of disease or
degeneration, and can help determine the location of
nerve lesions.
There are three major types of EP studies used
regularly:


Visual evoked potentials are used to diagnose visual
losses due to optic nerve damage, especially from
multiple sclerosis. They are also useful to diagnose

GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Evoked potential studies are painless, noninvasive, and without any significant risk. Somatosensory
EP tests involve very mild electric shocks, usually felt
as a tingling.

Description
The person performing the test locates and marks
specific spots on the patient’s head for placement of
electrodes. These spots are cleaned, and an adhesive
conducting paste is applied. Cup electrodes are
attached. For somatosensory EP, spots on the arm
or leg are also marked and cleaned; electrodes may
be taped in place. The patient sits or reclines in a chair
throughout the tests.
For a visual EP, the patient focuses on a TV screen
which displays a checkerboard pattern. The eye not
being tested is covered with a patch. For children or
others whose attention may wander, goggles are used
which show the pattern to one eye at a time. Each eye
is usually tested twice, and the entire procedure takes
approximately 30–45 minutes.
For auditory EP, headphones are used to deliver a
series of clicks to one ear at a time. A masking or static
1393

Evoked potential studies

Resources

Exercise

KEY TERMS
Nerve conduction velocity test—A test of the
speed of conduction of nerves, performed on the
nerves in the arm and leg.

that pathway. Other changes may provide evidence of
the type and location of nerve damage.
Resources
BOOKS

Samuels, Martin, and Seven Feske, editors. Office Practice
of Neurology. New York: Churchill Livingstone, 1996.

Richard Robinson
sound is played into the other ear. Each ear is usually
tested twice, and the entire procedure takes approximately 30–45 minutes.
For somatosensory EP, mild electrical shocks are
delivered to the arm or leg. This may cause some
twitching and tingling. The stimulus lasts for about
two minutes at a time, and the entire procedure takes
approximately 30 minutes.
After the tests, the electrodes are removed with
acetone and the scalp is cleaned.

Preparation
Hair must be clean, dry, and free of any braids,
pins, or jewelry. The patient should shampoo before
the test, and must not use any hair spray, gel, or other
hair care products after shampooing. Clothing should
be loose and comfortable. The patient may eat and
take some medications as usual before the test,
although sedative medications should be avoided on
the day of the test, if possible. It is best to check with
the physician supervising the test for specific
instructions.

Aftercare
This test is painless and has no residual effects.
The patient may return to work or other activities
immediately afterward.

Normal results
EP test results are displayed as jagged electrical
tracings (wave forms), which have characteristic
shapes, heights, and lengths, indicating the speed and
intensity of signal transmission. Results are read by
someone trained in evoked potential studies.

Abnormal results
Changes in the electrical tracings may indicate
damage to or degeneration of nerve pathways to the
brain from the eyes, ears, or limbs. Absence of any
activity may mean complete loss of nerve function in
1394

Evoked responses see Evoked potential
studies
Exanthema subitum see Roseola

Exercise
Definition
Exercise is physical activity that is planned, structured, and repetitive for the purpose of conditioning
any part of the body. Exercise is utilized to improve
health, maintain fitness and is important as a means of
physical rehabilitation.

Purpose
Exercise is useful in preventing or treating coronary heart disease, osteoporosis, weakness, diabetes,
obesity, and depression. Range of motion is one aspect
of exercise important for increasing or maintaining
joint function. Strengthening exercises provide appropriate resistance to the muscles to increase endurance
and strength. Cardiac rehabilitation exercises are
developed and individualized to improve the cardiovascular system for prevention and rehabilitation of
cardiac disorders and diseases. A well-balanced exercise program can improve general health, build endurance, and delay many of the effects of aging. The
benefits of exercise not only improve physical health,
but also enhance emotional well-being.
A study released in 2003 reported that exercise
combined with behavioral therapy may even help
manage the symptoms experienced by Gulf War veterans. Specifically, exercise helped improve symptoms
related to fatigue, distress, cognitive problems and
mental health functioning. In the same year, the
American Heart Association released a statement saying that exercise was beneficial even for patients awaiting heart transplants. Another study showed that
women who participated in strenuous physical activity
over a number of years could reduce their risk for
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Before beginning any exercise program, an evaluation by a physician is recommended to rule out any
potential health risks. Once health and fitness are
determined, and any or all physical restrictions identified, an individual’s exercise program should be under
the supervision of a health care professional. This is
particularly true when exercise is used as a form of
rehabilitation. If symptoms of dizziness, nausea, excessive shortness of breath, or chest pain are present during any exercise program, an individual should stop
the activity and inform a physician about these symptoms before resuming activity. Exercise equipment
must be checked to determine if it can bear the weight
of people of all sizes and shapes.

Description
Range of motion exercise
Range of motion exercise refers to activity aimed
at improving movement of a specific joint. This
motion is influenced by several structures: configuration of bone surfaces within the joint, joint capsule,
ligaments, and muscles and tendons acting on the
joint. There are three types of range of motion exercises: passive, active, and active assists. Passive range
of motion is movement applied to a joint solely by
another person or persons or a passive motion
machine. When passive range of motion is applied,
the joint of an individual receiving exercise is completely relaxed while the outside force moves the body
part, such as a leg or arm, throughout the available
range. Injury, surgery, or immobilization of a joint may
affect the normal joint range of motion. Active range
of motion is movement of a joint provided entirely by
the individual performing the exercise. In this case,
there is no outside force aiding in the movement.
Active assist range of motion is described as a joint
receiving partial assistance from an outside force. This
range of motion may result from the majority of
motion applied by an exerciser or by the person or
persons assisting the individual. It also may be a halfand-half effort on the joint from each source.
Strengthening exercise
Strengthening exercise increases muscle strength
and mass, bone strength, and the body’s metabolism.
GALE ENCYCLOPEDIA OF MEDICINE

It can help attain and maintain proper weight and
improve body image and self-esteem. A certain level
of muscle strength is needed to do daily activities, such
as walking, running and climbing stairs. Strengthening
exercises increase this muscle strength by putting more
strain on a muscle than it is normally accustomed to
receiving. This increased load stimulates the growth of
proteins inside each muscle cell that allow the muscle
as a whole to contract. There is evidence indicating
that strength training may be better than aerobic exercise alone for improving self-esteem and body image.
Weight training allows one immediate feedback,
through observation of progress in muscle growth
and improved muscle tone. Strengthening exercise
can take the form of isometric, isotonic and isokinetic
strengthening.
ISOMETRIC EXERCISE. During isometric exercises,
muscles contract. However, there is no motion in the
affected joints. The muscle fibers maintain a constant
length throughout the entire contraction. The exercises are usually performed against an immovable surface or object such as pressing one’s hand against a
wall. The muscles of the arm are contracting but the
wall is not reacting or moving as a result of the physical effort. Isometric training is effective for developing
total strength of a particular muscle or group of muscles. It often is used for rehabilitation since the exact
area of muscle weakness can be isolated and strengthening can be administered at the proper joint angle.
This kind of training can provide a relatively quick
and convenient method for overloading and strengthening muscles without any special equipment and with
little chance of injury.
ISOTONIC EXERCISE. Isotonic exercise differs from
isometric exercise in that there is movement of a joint
during the muscle contraction. A classic example of an
isotonic exercise is weight training with dumbbells and
barbells. As the weight is lifted throughout the range
of motion, the muscle shortens and lengthens.
Calisthenics are also an example of isotonic exercise.
These would include chin-ups, push-ups, and sit-ups,
all of which use body weight as the resistance force.
ISOKINETIC EXERCISE. Isokinetic exercise utilizes
machines that control the speed of contraction within
the range of motion. Isokinetic exercise attempts to
combine the best features of both isometrics and
weight training. It provides muscular overload at a
constant preset speed while a muscle mobilizes its
force through the full range of motion. For example,
an isokinetic stationary bicycle set at 90 revolutions
per minute means that despite how hard and fast the
exerciser works, the isokinetic properties of the bicycle
will allow the exerciser to pedal only as fast as 90

1395

Exercise

breast cancer. Finally, research showed that men and
women age 40 to 50 who exercised moderately for 60
to 90 minutes a day were less likely to catch a cold than
those who sat around.

Exercise

THREE TYPES OF EXERCISE

Stretching, for flexibility

Weight-bearing, for
strengthening muscles
and bone mass

Aerobic, for the heart

Exercise is utilized to improve health, maintain fitness, and is important as a means of physical rehabilitation. (Illustration by
Electronic Illustrators Group.)

revolutions per minute. Machines known as Cybex
and Biodex provide isokinetic results; they generally
are used by physical therapists.

program, proper stretching is important to prevent the
possibility of soft tissue injury resulting from tight
muscles, tendons, ligaments, and other joint-related
structures.

Cardiac rehabilitation
Exercise can be very helpful in prevention and
rehabilitation of cardiac disorders and disease. With
an individually designed exercise program set at a level
considered safe for the individual, people with symptoms of heart failure can substantially improve their
fitness levels. The greatest benefit occurs as muscles
improve the efficiency of their oxygen use, which
reduces the need for the heart to pump as much
blood. While such exercise doesn’t appear to improve
the condition of the heart itself, the increased fitness
level reduces the total workload of the heart. The
related increase in endurance also should translate
into a generally more active lifestyle. Endurance or
aerobic routines, such as running, brisk walking,
cycling, or swimming, increase the strength and efficiency of the muscles of the heart.

Aftercare
Proper cool down after exercise is important in
reducing the occurrence of painful muscle spasms. It
has been documented that proper cool down also may
decrease frequency and intensity of muscle stiffness
the day following any exercise program.

Risks
Improper warm up can lead to muscle strains.
Overexertion without enough time between exercise sessions to recuperate also can lead to muscle strains,
resulting in inactivity due to pain. Stress fractures also
are a possibility if activities are strenuous over long
periods of time without proper rest. Although exercise
is safe for the majority of children and adults, there is
still a need for further studies to identify potential risks.

Preparation
A physical examination by a physician is important to determine if strenuous exercise is appropriate
or detrimental for an individual. Prior to the exercise
1396

Normal results
Significant health benefits are obtained by including a moderate amount of physical exercise in the form
GALE ENCYCLOPEDIA OF MEDICINE

Roberts, Matt. 90-Day Fitness Plan. Littleton, CO: DK
Publishers, 2001.
PERIODICALS

Aerobic—Exercise training that is geared to provide a sufficient cardiovascular overload to stimulate increases in cardiac output.
Calisthenics—Exercise involving free movement
without the aid of equipment.
Endurance—The time limit of a person’s ability to
maintain either a specific force or power involving
muscular contractions.
Osteoporosis—A disorder characterized by loss of
calcium in the bone, leading to thinning of the
bones. It occurs frequently in postmenopausal
women.

of an exercise prescription. This is much like a drug
prescription in that it also helps enhance the health of
those who take it in the proper dosage. Physical activity plays a positive role in preventing disease and
improving overall health status. People of all ages,
both male and female, benefit from regular physical
activity. Regular exercise also provides significant psychological benefits and improves quality of life.
Studies released in 2003 showed the actual activity in
the brain promoted by regular aerobic exercise. It
appears that exercise also improves problem solving
and other brain-related abilities.

Abnormal results
There is a possibility of exercise burnout if an
exercise program is not varied and adequate rest periods are not taken between exercise sessions. Muscle,
joint, and cardiac disorders have been noted among
people who exercise. However, they often have had
preexisting or underlying illnesses.
Resources
BOOKS

Bookhout, Mark R., and Grenman, Philip. Principles of
Exercise Prescription. Woburn, MA: ButterworthHeinemann, 2001.
Harr, Eric. The Portable Personal Trainer. New York:
Broadway Books, 2001.
McArdle, William D., Frank I. Katch, and Victor L.
Katch. Exercise Physiology: Energy, Nutrition, and
Human Performance. 5th ed. Philadelphia:
Lippincott, 2001.
Redding, Morgan. Physical Fitness : Concepts and
Applications. Dubuque, IA: Kendall/Hunt
Publishing, 2001.
GALE ENCYCLOPEDIA OF MEDICINE

Brun, J. F., M. Dumortier, C. Fedou, and J. Mercier.
‘‘Exercise Hypoglycemia in Nondiabetic Subjects.’’
Diabetes and Metabolism 27 (2001): 92-106.
‘‘Cognitive Behavioral Therapy Plus Exercise May Alleviate
Symptoms.’’ Mental Health Weekly Digest (March 31,
2003): 3.
Evans, E. M., R. E. Van Pelt, E. F. Binder, D. B. Williams,
A. A. Ehsani, and W. M. Kohrt. ‘‘Effects of HRT and
Exercise Training on Insulin Action, Glucose
Tolerance, and Body Composition in Older women.’’
Journal of Applied Physiology 90 (2001): 2033-2040.
‘‘Exercise May Help Patients.’’ Heart Disease Weekly
(March 30, 2003): 44.
Killian, K. J. ‘‘Is Exercise Tolerance Limited by the Heart or
the Lungs?’’ Clinical Investigations in Medicine 24
(2001): 110-117.
Resnick, B. ‘‘Testing a model of exercise behavior in older
adults.’’ Research in Nursing and Health 24, no.2
(2001): 83-92.
‘‘Stay Active to Stay Cold-Free: A Recent Study Found that
You can Ward Off the Sniffle with a Little Exercise.’’
Natural Health (March 2003): 30.
‘‘Strenuous Physical Activity Throughout Life can Decrease
Risk .’’ Cancer Weekly (March 18, 2003): 32.
‘‘Study is First to Confirm Link Between Exercise and
Changes in Brain.’’ Obesity, Fitness and Wellness Week
(February 22, 2003): 13.
ORGANIZATIONS

American College of Sports Medicine. 401 W. Michigan
Street, Indianapolis, IN 46202-3233. (317) 637-9200.
Fax: (317) 634-7817. <http://www.acsm.org/>.
mkeckhaver@acsm.org.
American Medical Association. 515 N. State Street,
Chicago, IL 60610. (312) 464-5000. <http://www.
ama-assn.org/>.
American Physical Therapy Association. 1111 North
Fairfax Street Alexandria, VA 22314. (703) 684-2782.
<http://www.apta.org>.
National Athletic Trainers’ Association. 2952 Stemmons
Freeway, Dallas, TX 75247-6916. (800) 879-6282 or
(214) 637-6282. Fax: (214) 637-2206. <http://
www.nata.org/>.
OTHER

American Diabetes Association. <http://www.diabetes.org/
exercise>.
American Heart Association. <http://
www.americanheart.org>.
American Orthopaedic Society for Sports Medicine.
<http://www.sportsmed.org>.
American Society of Exercise Physiologists. <http://
www.css.edu/asep>.

L. Fleming Fallon, Jr., MD, DrPH
Teresa G. Odle
1397

Exercise

KEY TERMS

Exophthalmos

Exercise electrocardiogram see
Stress test
Exercise stress test see Stress test
Exhibitionism see Sexual perversions
Exocrine pancreatic cancer see Pancreatic
cancer, exocrine

Exophthalmos
Definition
When there is an increase in the volume of the
tissue behind the eyes, the eyes will appear to bulge out
of the face. The terms exophthalmos and proptosis
apply. Proptosis can refer to any organ that is
displaced forward, while exophthalmos refers just to
the eyes.

Description
The eye socket (orbit) is made of bone and therefore will not yield to increased pressure within it.
Only forward displacement of the eyeball (globe)
will allow more room if tissue behind the eye is
increasing.

Causes and symptoms
The most common cause of exophthalmos is
Graves’ disease, overactivity of the thyroid gland.
The contents of the orbits swell due to inflammation,
forcing the eyes forward. The inflammation affects
primarily the muscles. This combination of muscle
impairment and forward displacement reduces eye
movement, causing double vision and crossed eyes
(strabismus). The optic nerves can also be affected,
reducing vision, and the clear membrane (conjunctiva)
covering the white part of the eyes and lining the inside
of the eyelids can swell. Finally, the eyes may protrude
so far that the eyelids cannot close over them, leading
to corneal damage.
Exophthalmos from Graves’ disease is bilateral
(occurring on both sides), but not necessarily symmetrical. In contrast, exophthalmos from orbital
tumors or a blood clot in the brain happens on
only one side.
1398

A side view of the bulging eye (exophthalmos) of a person
suffering from thytoxicosis. Exophthalmos is caused by
swelling of the soft tissue in the eye socket, which forces
the eyeball to be pushed forward and the eyelids stretched
apart. (Photograph by Dr. P. Marazzi, Photo Researchers, Inc.
Reproduced by permission.)

Diagnosis
Exophthalmos is obvious when it is advanced
enough to cause complications. When there is doubt
in the early stages, a mechanical device called an
exophthalmometer can measure the protrusion.
Computed tomography scans (CT scans) are of great
value in examining the bony components of the orbit.
Magnetic resonance imaging (MRI) scanning is equally
valuable for displaying the contents of the orbit,
because it ‘‘sees through’’ the bone.

Treatment
If a tumor is growing behind the eye, it needs
to be removed. If Graves’ disease is the cause, it
may subside with treatment of the overactive thyroid, but this is not guaranteed. Local care to the
front of the eye to keep it moist is necessary if the
eyelid cannot close.

Prognosis
Exophthalmos can be progressive. Its progress
must be carefully followed, treating complications as
they occur.

Prevention
Vision can usually be preserved with attentive
treatment. There is currently no way to prevent any
of the underlying conditions that lead to
exophthalmos.
GALE ENCYCLOPEDIA OF MEDICINE

Conjunctivae—The clear membranes that line the
inside of the eyelids and cover the white part
(sclera) of the eyeballs.
Cornea—The clear, dome-shaped part of the front
of the eye, through which light first enters the eye. It
is located in front of the colored part of the eye (iris).
Inflammation—The body’s reaction to invasion by
foreign matter, particularly infection. The result is
swelling and redness from an increase in water and
blood, and pain from the chemical activity of the
reaction.
Strabismus—Any deviation of the eyes from a common direction. Commonly called a turned eye.
Thyroid—A gland in the neck overlying the windpipe that regulates the speed of metabolic processes by producing a hormone, thyroxin.

There are other ways to loosen and clear the
respiratory secretions associated with colds. These
include using a humidifier and drinking six to eight
glasses of water a day.

Description
Guaifenesin is an ingredient in many cough medicines, such as the brand names Anti-Tuss, Dristan
Cold & Cough, Guaifed, GuaiCough, and some
Robitussin products. Some products that contain
guaifenesin are available only with a physician’s prescription; others can be bought without a prescription.
They come in several forms, including capsules,
tablets, and liquids.

Recommended dosage
Adults and children 12 and over
200–400 mg every four hours. No more than 2,400
mg in 24 hours.
Children 6–11

Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

100–200 mg every four hours. No more than 1,200
mg in 24 hours.
Children 2–5

J. Ricker Polsdorfer, MD

50–100 mg every four hours. No more than 600
mg in 24 hours.
Children under two
Not recommended.

Expectorants
Definition
Expectorants are drugs that loosen and clear
mucus and phlegm from the respiratory tract.

Purpose
The drug described here, guaifenesin, is a common
ingredient in cough medicines. It is classified as an
expectorant, a medicine that helps clear mucus and
other secretions from the respiratory tract. However,
some debate exists about how effectively guaifenesin
does this. In addition, some cough medicines contain
other ingredients that may cancel out guaifenesin’s
effects. Cough suppressants such as codeine, for example, work against guaifenesin because they discourage
coughing up the secretions that the expectorant
loosens.
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Do not take more than the recommended daily
dosage of guaifenesin.
Guaifenesin is not meant to be used for coughs
associated with asthma, emphysema, chronic bronchitis, or smoking. It also should not be used for coughs
that are producing a large amount of mucus.
A lingering cough could be a sign of a serious
medical condition. Coughs that last more than seven
days or are associated with fever, rash, sore throat, or
lasting headache should have medical attention. Call a
physician as soon as possible.
Some studies suggest that guaifenesin causes birth
defects. Women who are pregnant or plan to become
pregnant should check with their physicians before
using any products that contain guaifenesin.
Whether guaifenesin passes into breast milk is not
1399

Expectorants

KEY TERMS

External sphincter electromyography

External sphincter
electromyography

KEY TERMS
Asthma—A disease in which the air passages of the
lungs become inflamed and narrowed.
Bronchitis—Inflammation of the air passages of the
lungs.
Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Cough suppressant—Medicine that stops or prevents coughing.
Emphysema—An irreversible lung disease in which
breathing becomes increasingly difficult.
Mucus—Thick fluid produced by the moist membranes that line many body cavities and structures.
Phlegm—Thick mucus produced in the air
passages.
Respiratory tract—The air passages from the nose
into the lungs.
Secretion—A substance, such as saliva or mucus,
that is produced and given off by a cell or a gland.

Definition
External sphincter electromyography helps physicians determine how well the external urinary sphincter muscle is working by measuring the electrical
activity in it during contraction and relaxation.

Purpose
The external sphincter muscle is the ring-like muscle that controls urine release from the bladder. When
a patient cannot voluntarily control urination (incontinence), a physician may order this test to determine if
the problem is caused by the failure of this muscle. The
voluntary contraction or release of a muscle such as
the external sphincter involves a complex process in
which the nerves controlling the muscle signal it to
move through the release and uptake of chemicals
called neurotransmitters and the generation of electrical impulses. This test records the electrical impulses
given off when the muscle contracts or relaxes and
allows the physician to determine if the muscle is
working properly, if it has been damaged by disease,
or some other condition.

known, but no ill effects have been reported in nursing
babies whose mothers used guaifenesin.

Side effects
Side effects are rare, but may include vomiting,
diarrhea, stomach upset, headache, skin rash, and
hives.

Precautions
Patients who are taking muscle relaxants or drugs
that act like or have an effect on the neurotransmitter
acetylcholine (cholinergic or anti-cholinergic drugs)
should tell the doctor since they will change the test results.
The results will also be altered if the patient moves during
the test or if the electrodes are improperly placed.

Interactions
Guaifenesin is not known to interact with any
foods or other drugs. However, cough medicines that
contain guaifenesin may contain other ingredients that
do interact with foods or drugs. Check with a physician or pharmacist for details about specific products.
Nancy Ross-Flanigan

Description
The patient puts on a surgical gown and lies down
on the examining table. The procedure, which takes
between 30–60 minutes, may be conducted one of
three ways:


Skin electrodes. This is the most commonly used
method of recording information. The skin where
the electrodes will be placed is cleaned and shaved
and an electrically conductive paste is applied. The
electrodes are then taped in place. For female
patients, the electrodes are taped around the urethra,
while for male patients they are placed between the
scrotum and the anus.



Needle electrodes. This is considered the most accurate method, since the electrodes are inserted directly

Exstrophy of the urinary bladder see
Congenital bladder anomalies
External fetal monitoring see Electronic fetal
monitoring
External otitis see Otitis externa
1400

GALE ENCYCLOPEDIA OF MEDICINE



KEY TERMS
Anti-cholinergic drug—A medication that blocks
or subdues the action of the neurotransmitter
acetylcholine.
Cholinergic drug—A medication that mimics or
enhances the action of the neurotransmitter
acetylcholine.

Anal plug electrodes. The tip of an anal plug is
lubricated and inserted into the rectum as the patient
relaxes the anal sphincter. Electrodes are attached to
the anal plug.

Once the electrodes are in place and attached to
the recording device, the patient is asked to alternately
contract and relax the external sphincter muscle. The
electrical activity generated during these contractions
and relaxations is recorded on a graph called an
electromyogram.

Preparation
Before the test, the patient should discuss with the
doctor whether it is necessary to temporarily discontinue any medications, and follow the doctor’s orders.
No changes in diet or activity are necessary.

Sphincter—A circular muscle that aids in the opening or closing of an opening in the body.

that affect the external sphincter may include multiple
sclerosis, neurogenic bladder, Parkinson’s disease,
spinal cord injury, and stress incontinence. However,
additional tests must be done in order to confirm any
of these diagnoses.
Resources
BOOKS

Lewis, J. A., editor. ‘‘External Sphincter
Electromyography.’’ In Illustrated Guide to Diagnostic
Tests. Springhouse, PA: Springhouse Corp., 1994.

Tish Davidson, A.M.

Aftercare
Women may see some blood in their urine the first
time they urinate after the test. Blood in the urine of
men or blood in the urine of women after the first
urination should be reported the doctor. The patient
should take a warm bath and drink plenty of fluids to
ease any discomfort after the test.

Extracorporeal membrane
oxygenation
Definition

Risks
Complications of external sphincter electromyography are rare. Occasionally patients report blood in
their urine after being tested with needle electrodes.
Also, the urethra may become mildly irritated causing
a change in the normal frequency of urination.

Normal results
In a normally functioning external sphincter muscle, the electromyogram will show increased electrical
activity when the patient tightens the muscle and a
little or no electrical activity when it is relaxed.

Abnormal results
A diseased external sphincter muscle will produce
an abnormal pattern of electrical activity. Conditions
GALE ENCYCLOPEDIA OF MEDICINE

Extracorporeal membrane oxygenation (ECMO)
is a special procedure that uses an artificial heart-lung
machine to take over the work of the lungs (and sometimes also the heart). ECMO is used most often in
newborns and young children, but it also can be used
as a last resort for adults whose heart or lungs are
failing.

Purpose
In newborns, ECMO is used to support or replace
an infant’s undeveloped or failing lungs by providing
oxygen and removing carbon dioxide waste products
so the lungs can rest. Infants who need ECMO may
include those with:


meconium aspiration syndrome, (breathing in of a
newborn’s first stool by a fetus or newborn, which
1401

Extracorporeal membrane oxygenation

into the muscle, using needles to guide placement.
For male patients, a gloved finger is inserted in the
rectum, then needles with wires attached are inserted
through the skin between the anus and the scrotum.
For female patients, the needles are inserted around
the urethra. The discomfort of placing the needles is
about the same as that of an injection. The needles
are withdrawn, and the wires are taped to the thigh.

Extracorporeal membrane oxygenation

can block air passages and interfere with lung
expansion)

problems. Venovenous (V-V) ECMO supports the
lungs only.



persistent pulmonary hypertension, (a disorder in
which the blood pressure in the arteries supplying
the lungs is abnormally high)



respiratory distress syndrome (a lung disorder
usually of premature infants that causes increasing
difficulty in breathing, leading to a life-threatening
deficiency of oxygen in the blood)

V-A ECMO requires the insertion of two tubes,
one in the jugular and one in the carotid artery. In the
V-V ECMO procedure, the surgeon places a plastic
tube into the jugular vein through a small incision in
the neck.



congenital diaphragmatic hernia, (the profusion of
part of the stomach through an opening in the
diaphragm)



pneumonia



blood poisoning

ECMO is also used to support a child or adult
patient’s damaged, infected, or failing lungs for a few
hours to allow treatment or healing. It is effective for
those patients with severe, but reversible, heart or lung
problems who haven’t responded to treatment with a
ventilator, drugs, or extra oxygen. Adults and children
who need ECMO usually have one of these problems:


heart failure



pneumonia



respiratory failure caused by trauma or severe
infection

The ECMO procedure can help a patient’s lungs
and heart rest and recover, but it will not cure the
underlying disease. Any patient who requires ECMO
is seriously ill and will likely die without the treatment.
Because there is some risk involved, this method is
used only when other means of support have failed.

Precautions
Typically, ECMO patients have daily chest x rays
and blood work, and constant vital sign monitoring.
They are usually placed on a special rotating bed that
is designed to decrease pressure on the skin and help
move secretions from the lungs.
After the patient is stable on ECMO, the breathing machine settings will be lowered to ‘‘rest’’ settings,
which allows the lungs to rest without the risk of too
much oxygen or pressure from the ventilator.

Description
There are two types of ECMO: Venoarterial
(V-A) ECMO supports the heart and lungs, and is
used for patients with blood pressure or heart functioning problems in addition to respiratory
1402

Once in place, the tubes are connected to the
ECMO circuit, and then the machine is turned on.
The patient’s blood flows out through the tube and
may look very dark because it contains very little
oxygen. A pump pushes the blood through an artificial
membrane lung, where oxygen is added and carbon
dioxide is removed. The size of the artificial lung
depends on the size of the patient; sometimes adults
need two lungs. The blood is then warmed and
returned to the patient. A steady amount of blood
(called the flow rate) is pushed through the ECMO
machine every minute. As the patient improves, the
flow rate is lowered.
Many patients require heavy sedation while they
are on ECMO to lessen the amount of oxygen needed
by the muscles.
As the patient improves, the amount of ECMO
support will be decreased gradually, until the
machine is turned off for a brief trial period. If the
patient does well without ECMO, the treatment is
stopped.
Typically, newborns remain on ECMO for three
to seven days, although some babies need more time
(especially if they have a diaphragmatic hernia).
Once the baby is off ECMO, he or she will still need
a ventilator (breathing machine) for a few days or
weeks. Adults may remain on ECMO for days to
weeks, depending on the condition of the patient,
but treatment may be continued for a longer time
depending on the type of heart or lung disease, the
amount of damage to the lungs before ECMO was
begun, and the presence of any other illnesses or
health problems.

Preparation
Before ECMO is begun, the patient receives medication to ease pain and restrict movement.

Aftercare
Because infants on ECMO may have been struggling with low oxygen levels before treatment, they
may be at higher risk for developmental problems.
They will need to be monitored as they grow.
GALE ENCYCLOPEDIA OF MEDICINE

Carotid artery—Two main arteries (passageway
carrying blood from the heart to other parts of the
body) that carry blood to the brain.
Congenital diaphragmatic hernia—The profusion
of part of the stomach through an opening in the
diaphragm.

causing damage or death of vital organs (including the
brain). For this reason, the ECMO circuit is constantly monitored by a trained technologist.

Normal results
Lungs and/or heart return to healthy functioning.

Abnormal results

Meconium aspiration syndrome—Breathing in of
meconium (a newborn’s first stool) by a fetus or
newborn, which can block air passages and interfere with lung expansion.

Lungs and/or heart do not improve while on
ECMO.

Membrane oxygenator—The artificial lung that
adds oxygen and removes carbon dioxide.
Pulmonary hypertension—A disorder in which the
blood pressure in the arteries supplying the lungs is
abnormally high.

ORGANIZATIONS

Respiratory distress syndrome—A lung disorder
usually of premature infants that causes increasing
difficulty in breathing, leading to a life-threatening
deficiency of oxygen in the blood.
Venoarterial (V-A) bypass—The type of ECMO that
provides both heart and lung support, using two
tubes (one in the jugular vein and one in the carotid
artery).
Venovenous (V-V) bypass—The type of ECMO that
provides lung support only, using a tube inserted
into the jugular vein.

Resources
American Society of Extra-Corporeal Technology. 11480
Sunset Hills Rd., Ste. 210E, Reston, VA 20190. (703)
435-8556. <http://www.amsect.org>.
ECMO Moms and Dads. PO Box 53848, Lubbock, TX
79543. (806) 794-0259.
Extracorporeal Life Support Organization. 1327 Jones Dr.,
Ste. 101, Ann Arbor, MI 48105. (734) 998-6600.
<http://www.elso.med.umich.edu>.

Carol A. Turkington

Extracorporeal shock-wave see Lithotripsy
Extrinsic allergic alveolitis see
Hypersensitivity pneumonitis
Eye and orbit sonograms see Eye and orbit
ultrasounds

Risks
Bleeding is the biggest risk for ECMO patients,
since blood thinners are given to guard against blood
clots. Bleeding can occur anywhere in the body, but is
most serious when it occurs in the brain. This is why
doctors periodically perform ultrasound brain scans
of anyone on ECMO. Stroke, which may be caused by
bleeding or blood clots in the brain, has occurred in
some patients undergoing ECMO.
If bleeding becomes a problem, the patient may
require frequent blood transfusions or operations to
control the bleeding. If the bleeding can’t be stopped,
ECMO will be withdrawn.
Other risks include infection or vocal cord injury.
Some patients develop severe blood infections that
cause irreversible damage to vital organs.
There is a small chance that some part of the
complex equipment may fail, which could introduce
air into the system or affect the patient’s blood levels,
GALE ENCYCLOPEDIA OF MEDICINE

Eye and orbit ultrasounds
Definition
Ultrasound imaging equipment allows eye specialists (ophthalmologists) to ‘‘see’’ the eye in great detail
without the pain and risk of exploratory surgery, or the
limitations and uncertainty inherent to traditional
visual examination. Ultrasound is used to detect and
diagnose many eye diseases and injuries, to measure
the eye prior to corrective surgery, and directly as a
treatment tool.

Purpose
An ophthalmologist uses ultrasonic imaging to
help diagnose the underlying cause(s) of a patient’s
symptoms, to assess the general condition of an
injured eye, and to measure the eye prior to corrective
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Eye and orbit ultrasounds

KEY TERMS

Eye and orbit ultrasounds

surgery. Situations that may call for ultrasonic imaging include:




Excessive tearing or visible infection. These external
symptoms could indicate a serious underlying problem such as a tumor, an internal infection, the presence of a deeply lodged irritant (foreign body), or
the effects of a previously unrecognized injury. When
presented with general symptoms, ultrasound can
speed diagnosis if a serious condition is suspected.
Impaired vision. Fuzzy vision, poor night vision,
restricted (tunnel) vision, blind spots, extreme light
sensitivity, and even blindness can all stem from
inner eye conditions ranging from glaucoma and
cataracts, to retinitis, detached retina, tumors, or
impaired blood circulation. Again, high resolution
ultrasound can quickly identify causes and pinpoint
their location. A special type of ultrasound, known
as Doppler, can even perceive and measure circulation in the tiny blood vessels of the eye.



Eye trauma. The eye can be damaged by a direct
impact or a puncture wound, as a result of a general
head trauma, or by intense light exposure. Even
when the cause of injury is obvious, ultrasound can
reveal the exact type, extent, and location of damage,
from deformations and ruptures to internal bleeding,
and help to guide emergency care efforts.



Lens replacement surgery. Exact measurement of the
eye’s optical dimensions with ultrasound greatly
improves the visual outcome for cataract patients
receiving permanent synthetic lenses; and for
severely myopic patients receiving implanted corrective lenses.

Ophthalmic ultrasound imaging is also used routinely to guide the precise placement of instruments
during surgery, and can be used directly for the treatment of glaucoma and tumors of the eye.

computer to produce an image on a television
screen. The time it takes an echo to return to the
receiver corresponds to the depth it traveled into
the eye.
Single transducer (the sound transmitter/receiver)
ultrasound is used to measure distances within the eye.
This is A-mode ultrasound. A linear array of transducers in a single small probe, B-mode, provides a picture
of a cross section through the eye. Doppler mode
ultrasound combines B-mode with the ability to detect
and measure the flow of blood in the tiny vessels of
the eye.
As a direct treatment tool, the vibrations of high
intensity A-mode ultrasound can be used to heat and
erode tumors. The same technique can be used to
control glaucoma by selectively destroying the cells
which produce the fluid that causes the internal pressure of the eye to rise.
The procedure followed in a regular ultrasonic eye
examination is relatively simple. The patient relaxes in
a comfortable chair in a darkened room. Mild anesthetic eye drops are administered and the head is held
secure. The ultrasonic probe, coated with a sterile gel
to ensure good contact, is lightly pressed against the
eye as the images are made. The probe may be applied
to the eyelid or directly to the eye, as necessary. The
patient feels nothing else, and the whole office procedure takes about 15 minutes.

Preparation
Preparation by the patient is generally unnecessary, although under special circumstances an
ophthalmologist may perform pretest procedures.
The ophthalmologist and/or ultrasound technician
will conduct all preparations at the time of the test.

Aftercare
Precautions
Ultrasound of the eye, properly performed by
qualified personnel using appropriate equipment, has
no risks. There is no evidence to suggest that the
procedure itself poses any threat to a healthy eye, or
worsens the condition of a diseased or injured eye.

Description
Ophthalmic ultrasound equipment sends high
frequency pulses of sound into the eye, where they
bounce off the boundaries between different structures
in the eye and produce a distinctive pattern of echoes.
This echo pattern is received and interpreted by a
1404

Patients may experience partial and temporary
blurred vision, as well as ‘‘eye strain’’ headaches.
These symptoms usually fade within an hour of the
procedure, during which time patients should rest
their eyes and avoid all activities that require good
eyesight, like driving.

Risks
Improperly focused, high-intensity ultrasound
could burn and physically disrupt delicate eye tissue
and cause injury. This risk is, however, slight and
would arise only from improper use, or as a potential
side effect of tumor or glaucoma treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Cataracts—A clouding of the lens of the eye or the
material immediately surrounding it, causing
blurred vision. For many people it occurs naturally
with aging, but may also result from injury.
Glaucoma—A common eye disease characterized
by increased fluid pressure in the eye that damages
the optic nerve, which carries sensations to the
brain. Glaucoma can be caused by another eye
disorder, such as a tumor or congenital malformation, or appear without obvious cause, but if
untreated it generally leads to blindness.
Intraocular—Literally, within the eye.
Ophthalmologist—A medical doctor specializing
in eye care who is generally, but not necessarily,
an eye surgeon.
Retina—The third and innermost membrane of the
eye, which contains the light-sensitive nerve tissue
that leads into the optic nerve and is the primary
instument of vision. Inflammation of the retina
(retinitis) has many causes, including overexposure to intense light, diabetes, and syphilis.

Normal results
A normal ultrasound scan would indicate a fully
healthy eye. For therapeutic ultrasound, a normal
result would be an improvement in the targeted condition, such as shrinking of a tumor or lessening of
pressure inside the eye of a glaucoma patient.

Abnormal results
Because diagnostic ultrasound is generally used to
investigate symptoms, the results of a scan will often
be abnormal and they will detect evidence of an underlying condition.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
PO Box 7424, San Francisco, CA 94120-7424. <http://
www.eyenet.org>.
American Institute of Ultrasound in Medicine. 14750
Sweitzer Lane, Suite 100, Laurel, MD 20707-5906.
(800) 638-5352. <http://www.aium.org>.
National Eye Institute. 2020 Vision Place, Bethesda, MD
20892-3655. (301) 496-5248. <http://www.nei.nih.gov>.

Kurt Richard Sternlof
GALE ENCYCLOPEDIA OF MEDICINE

Eye cancer

KEY TERMS

Eye cancer
Definition
Eye cancer refers to a cancerous growth in any
part of the eye. Some eye cancers are primary, while
others represent metastases from primary cancers elsewhere in the body.
All types of eye cancer are rare in comparison to
other cancerous tumors. According to the American
Cancer Society, 2,090 people in the United States will
be diagnosed with cancer of the eye or orbit in 2004,
and 180 persons will die from the disease.

Description
Eye cancers can be grouped into three basic categories according to their location in the eye: tumors of
the eyelid and conjunctiva; intraocular tumors; and
orbital tumors. This article will focus on retinoblastoma, the most common eye cancer in children, and
intraocular melanoma, the most common eye cancer
in adults.
Retinoblastoma can occur at any age but is most
often seen in children younger than five. About 200
children a year are diagnosed with it in the United
States. Retinoblastoma starts with a small tumor in
the retina, the tissue that lies at the very back of the
eye. In growing children, the retina originates from
cells called retinoblasts that grow and divide very
quickly. These cells eventually become the mature
cells of the retina when they stop growing. In the
case of retinoblastoma the retinoblasts don’t stop
growing and form a tumor that can continue to grow
and cause further complications if not treated quickly.
Retinoblastoma typically has three classifications:
intraocular, extraocular and recurrent retinoblastoma. In the intraocular form the cancer can be
found in one or both eyes but not in tissue external
of the eye. In the extraocular form the cancer has
spread outside the eye. It can spread to the tissue
surrounding the eye or it can invade other areas of
the body. In the recurrent form the cancer returns after
already being treated. It may recur in the eye, its
surrounding tissues, or elsewhere in the body.
Intraocular melanoma is a rare cancer overall, yet
it is the most common eye cancer seen in adults.
Intraocular melanoma occurs when cancer cells are
found in the uvea of the eye. The uvea includes the
iris (the colored portion of eye), the ciliary body
(an eye muscle that focuses the lens) and the choroid
(found in the back of the eye next to the retina).
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Eye cancer

Intraocular cancer of the iris usually grows slowly
and usually doesn’t spread. The tumor is seen on the
iris as a darker spot than the surrounding area.
Intraocular cancer of the choroid or ciliary body
occurs in the back of the eye. They are classified by
size with a small tumor being 2-3 mm or smaller and a
medium or large tumor being bigger than 3 mm.

through the pupil. The tumor will show up in these
photos.

Intraocular cancer can spread and become extraocular as well. If not found and treated early enough it
can spread to the surrounding tissues, the optic nerve
or into the orbit (eye socket).

The treatment depends on how far advanced the
tumor is. If the tumor is in the advanced stages and
there is little hope of regaining vision the most effective
treatment is an enucleation, the removal of the eye.
Enucleation obviously is a drastic treatment and is
avoided if possible. Other eye surgeries include the
following:

Causes and symptoms
Genetics is thought to play a role in eye cancer. In
regards to retinoblastoma, it is believed that if a tumor
develops only in one eye then it isn’t hereditary.
However, if a tumor occurs in both eyes then it is
hereditary. Those who have hereditary retinoblastoma
have a rare risk of developing a tumor in the brain and
should be monitored on a regular basis.
The causes of intraocular melanoma are not fully
understood as of the early 2000s. Age is a factor as well
as genetic inheritance. In 2004, a group of ophthalmologists in Scotland identified mutations in the BRAF
gene in samples of tissue taken from conjunctival melanomas. Interestingly enough, this type of cancer is
seen most often in white people from a northern
European descent.
The symptoms of this type of cancer usually begin
with blurred vision and tenderness of the eye.
Advanced symptoms may include loss of vision. If
these symptoms persist a person should make an
appointment with an eye specialist.

Diagnosis
The diagnosis of eye cancer is usually made by an
ophthalmologist, who is a doctor who specializes in
treating eye disorders. In the case of cancerous
growths, the doctor is usually able to see the tumor
through the pupil or directly on the iris if the cancer is
intraocular melanoma of the iris. Because the doctor
can usually readily see the tumor a biopsy is rarely
needed.
An ultrasound or a fluorescein angiography are
two tests doctors use to further diagnose eye cancers.
In an ultrasound sound waves are pointed at the tumor
and depending on how they reflect off the tumor the
doctor can better diagnose it. In a fluorescein angiography a fluorescent dye is injected into the patients
arm. When this dye circulates through the body and
reaches the eye a series of rapid pictures are taken
1406

Once a diagnosis has been made, the treatment
can begin.

Treatment



choroidectomy: removal of part of the choroid



iridectomy: removal of part of the iris



iridocyclectomy: removal of parts of the ciliary body
and parts of iris



iridotrabeculectomy: removal of parts of the supporting tissues around the cornea and iris

In eye cancer where the tumor is small and there
is a good chance that the vision will be restored less
drastic measures than the above surgeries are taken.
Radiation and chemotherapy are two courses of
treatment that help in killing off the existing tumor
and preventing its spread into other areas of the
body. Specific anticancer drugs that are used in treating melanomas of the eye include gemcitabine and
treosulfan.
Besides radiation and chemotherapy there are
other methods of treating eye cancer. Cryotherapy
uses extreme cold to destroy the cancer cells.
Thermotherapy uses heat from a laser to destroy the
cancer cells. Photocoagulation uses a laser to destroy
blood vessels that supply the tumor with nutrients. If
the tumor isn’t advanced these are good options to
treat it in order to avoid losing an eye. The chief drawback of thermotherapy is that some visual acuity may
be lost in the treated eye.
A radiation/surgical treatment for eye cancer is
brachytherapy. A small plaque with radioactive
iodine on one side and gold on the other is stitched
to the eye behind the tumor with the radioactive
iodine facing the tumor. The gold is used to shield
the other tissues from the radiation. It is left there for
a period of time depending on the dosage of radiation needed and then it is removed. Although iodine
brachytherapy is effective in treating melanoma of
the eye, it increases the patient’s risk of developing a
cataract or glaucoma.
GALE ENCYCLOPEDIA OF MEDICINE

Brachytherapy—A type of radiation treatment for
cancer in which the source of the radiation is
applied directly to the surface of the body.
Carcinogen—A substance that is known to cause
cancer.
Conjunctiva—The thin membrane that lines the
eyelids.
Cornea—The transparent front portion of the exterior cover of the eye.
Enucleation—Surgical removal of the eyeball.
Iris (plural, irides)—The circular pigmented membrane behind the cornea of the eye that gives the
eye its color. The iris surrounds a central opening
called the pupil.
Ocular melanoma—A malignant tumor that arises
within the structures of the eye. It is the most common eye tumor in adults.
Ophthalmology—The branch of medicine that
deals with the diagnosis and treatment of eye
disorders.
Orbit—The bony cavity that contains the eyeball.
Pupil—The opening in the center of the iris of the
eye that allows light to enter the eye.
Uvea—The middle of the three coats of tissue surrounding the eye, comprising the choroid, iris, and
ciliary body. The uvea is pigmented and well supplied with blood vessels.

Prognosis
All forms of retinoblastoma and intraocular melanoma are treatable. Enucleation can usually be
avoided if the tumor is found early enough. In addition, primary cancers of the eye have a relatively low
mortality rate if treated promptly.

Clinical trials
As of 2004, the National Cancer Institute is sponsoring 10 clinical trials of treatments for ocular melanoma in adults and 5 trials for treatments of
retinoblastoma in children. These trials allow
researchers to investigate new types of radiation therapy and chemotherapy, new drugs and drug combinations, biological therapies, ways of combining various
types of treatment for eye cancer, side effect reduction,
and quality of life. Information on specific clinical
GALE ENCYCLOPEDIA OF MEDICINE

trials can be acquired from the National Cancer
Institute at <http://www.nci.nih.gov> or (800)
4-CANCER.

Prevention
Retinoblastoma is not preventable. In addition,
most other types of eye tumors are thought to be
partly genetic as of the early 2000s.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Principles of Cancer Therapy. ’’ Section 11, Chapter
144 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 1999.
PERIODICALS

Garcia-Valenzuela, Enrique, MD, PhD, and Mauricio E.
Pons, MD. ‘‘Melanoma, Choroidal.’’ eMedicine [cited
August 1, 2004]. <http://www.emedicine.com/oph/
topic403.htm>.
Gear, H., H. Williams, E. G. Kemp, and F. Roberts. ‘‘BRAF
Mutations in Conjunctival Melanoma.’’ Investigative
Ophthalmology and Visual Science 45 (August 2004):
2484–2488.
Keilholz, U., R. Schuster, A. Schmittel, et al. ‘‘A Clinical
Phase I Trial of Gemcitabine and Treosulfan in Uveal
Melanoma and Other Solid Tumours.’’ European
Journal of Cancer 40 (September 2004): 2047–2052.
Kiratli, H., and S. Bilgic. ‘‘Transpupillary Thermotherapy in
the Management of Choroidal Metastases.’’ European
Journal of Ophthalmology 14 (September-October
2004): 423–429.
Mercandetti, Michael, MD, and Adam J. Cohen, MD.
‘‘Tumors, Orbital.’’ eMedicine [cited December 14,
2004]. <http://www.emedicine.com/oph/
topic758.htm>.
Puusaari, I., J. Heikkonen, and T. Kivela. ‘‘Ocular
Complications after Iodine Brachytherapy for Large
Uveal Melanomas.’’ Ophthalmology 111 (September
2004): 1768–1777.
Shields, C. L., H. Demirci, E. Karatza, and J. A. Shields.
‘‘Clinical Survey of 1643 Melanocytic and
Nonmelanocytic Conjunctival Tumors.’’
Ophthalmology 111 (September 2004): 1747–1754.
ORGANIZATIONS

American Academy of Ophthalmology. P. O. Box 7424, San
Francisco, CA 94120-7424. (415) 561-8500. <http://
www.aao.org>.
American Cancer Society. 1599 Clifton Rd. NE, Atlanta,
GA 30329. (800) 227-2345. <http://www.cancer.org>.
Canadian Ophthalmological Society (COS). 610-1525
Carling Avenue, Ottawa ON K1Z 8R9. <http://
www.eyesite.ca:>.
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Eye cancer

KEY TERMS

Eye examination

National Eye Institute. 2020 Vision Place, Bethesda, MD
20892-3655. (301) 496-5248. <http://
www.nei.nih.gov>.
Ocular Oncology Service, Wills Eye Hospital. 840 Walnut
Street, Philadelphia, PA 19107. (215) 928-3000.
<http://www.willseye.org>.
OTHER

American Cancer Society (ACS). Cancer Facts & Figures
2004. <http://www.cancer.org/downloads/STT/
CAFF_finalPWSecured.pdf>.
Cancer Net. 2001. <http://www.cancernet.nci.nih.gov>.
Eye Cancer Info. Separate web site of the Ocular Oncology
Service at Wills Eye Hospital. <http://eyecancerinfo.
com/>.
JHMI. 2001 <http://www.med.jhu.edu>.
National Cancer Institute (NCI) Physician Data Query
(PDQ). Intraocular (Eye) Melanoma: Treatment.
January 2, 2003. <http://www.nci.nih.gov/cancerinfo/
pdq/treatment/intraocularmelanoma/
healthprofessional>.

Thomas Scott Eagan
Ronald Watson, PhD
Rebecca J. Frey, PhD

Eye examination
Definition
An eye examination is a series of tests that measure a person’s ocular health and visual status, to
detect abnormalities in the components of the visual
system, and to determine how well the person can see.

Purpose
An eye examination is performed by an ophthalmologist, (M.D. or D.O. -doctor of osteopathy), or an
optometrist (O.D.) to determine if there are any preexisting or potential vision problems. Eye exams may
also reveal the presence of many non-eye diseases.
Many systemic diseases can affect the eyes, and since
the blood vessels on the retina are observed during the
exam, certain problems may be uncovered (e.g., high
blood pressure or diabetes).
Infants should be examined by a physician to
detect any physical abnormalities. Frequency of eye
exams then generally differs with age and the health of
the person. Eye exams can be performed in infants,
and if a problem is noted the infant can be seen, generally by a pediatric ophthalmologist. A child with no
symptoms should have an eye exam at age three. Early
1408

exams are important because permanent decreases in
vision (e.g., amblyopia, also called lazy eye) can occur
if not treated early (usually by ages 6–9). Again, with
no other symptoms, the second exam should take
place before first grade. After first grade, the
American Optometric Association recommends an
eye exam every two years; ages 19–40, every two to
three years; ages 41–60, every two years; and annually
after that. However, these are recommendations for
healthy people with no risk factors. Patients should
ask their doctors how often they should come for
exams. Some patients have risk factors for eye disease
(e.g., people with diabetes or a family history of eye
disease; African Americans, who are at higher risk for
glaucoma) and may need more frequent checkups.
Also, if children seem to be having trouble in school,
problems with reading, rubbing their eyes when reading, etc., an eye exam may be necessary sooner.

Precautions
The examiner needs to know if the patient is taking any medications or has any existing health conditions. Some medications, even over-the-counter
(OTC) medications can affect vision or even interfere
with the eyedrops the doctor may use during the exam.
Certain eyedrops would not be used if the patient has
asthma, heart problems, or other conditions.
The patient may need someone to drive them
home in case the eyes were dilated. Bringing sunglasses
to the exam may also help decrease the glare from light
until the dilating drops wear off.

Description
An eye examination, given by an ophthalmologist
or optometrist, costs about $100. It may or may not be
covered by insurance. It begins with information from
the patient (case history) and continues with a set of
primary tests, plus additional specialized tests given as
needed, dictated by the outcomes of initial testing and
the patient’s age. The primary tests can be divided into
two groups, those that evaluate the physical state of
the eyes and surrounding areas, and those that measure the ability to see.
The order of the tests for the exam may differ from
doctor to doctor, however, most exams will include the
following procedures:
Information gathering and initial observations
The examiner will take eye and medical histories
that include the patient’s chief complaint, any past eye
disorders, all medications being taken (e.g., OTC
GALE ENCYCLOPEDIA OF MEDICINE

The patient should bring their current pair of
glasses to the exam. The doctor can get the prescription from the glasses by using an instrument called a
lensometer.
Visual acuity examination
Visual acuity measures how clearly the patient can
see. It is measured for each eye separately, with and
without the current prescription. It is usually measured with a Snellen eye chart, a poster with lines of
different-sized letters, each line with a number at the
side denoting the distance from which a person with
normal vision can read that line. Other kinds of eye
charts with identifiable figures are available for children or anyone unfamiliar with the Roman alphabet.
These charts are made to be placed at a certain distance (usually 20 ft) from the person being tested. At
this distance, people with normal vision can read a
certain line (usually the lowest), marked the 20/20
line; these people are said to have 20/20 vision. For
people who can’t read the smallest line, the examiner
assigns a ratio based on the smallest line they can read.
The first number (numerator) of the ratio is the distance between the chart and the patient, and the second number (denominator) is the distance where a
person with normal vision would be able to read that
line. The ratio 20/40 means the patient can see at 20 ft.
what people with normal vision can see at 40 ft. away.
When a patient is unable to read any lines on the
chart, they are moved closer until they can read the
line with the largest letters. The acuity is still measured
the same way. A ratio of 5/200 means the person being
tested can see at 5 ft what a normal person can see
200 ft.
When a patient cannot read the chart at all, the
examiner may hold up some fingers and ask the
patient to count them at various distances, and records
the result as ‘‘counting fingers’’ at the distance of
recognition. If the patient cannot count the examiner’s
fingers at any distance, the examiner determines if the
patient can see hand movements. If so, the result is
recorded as ‘‘hand movements.’’ If not, the examiner
GALE ENCYCLOPEDIA OF MEDICINE

determines if the patient can detect light from a penlight. If the patient can detect the light but not its
direction, the result is recorded at ‘‘light perception.’’
If the patient can recognize its direction, the result is
recorded as ‘‘light projection.’’ If the patient cannot
detect the light at all, the result is recorded as ‘‘no light
perception.’’
Eye movement examination and cover tests
The examiner asks the patient to look up and
down, and to the right and left to see if the patient
can move the eyes to their full extent. The examiner
asks the patient to stare at an object, then quickly
covers one eye and notes any movement in the eye
that remains uncovered. This procedure is repeated
with the other eye. This, and another similar cover
test, helps to determine if there is an undetected eye
turn or problem with fixation. The doctor may also
have the patient look at a pen and follow it as it is
moved close to the eyes. This checks convergence.
Iris and pupil examination
The doctor checks the pupil’s response to light
(if it dilates and constricts appropriately). The iris is
viewed for symmetry and physical appearance. The
iris is checked more thoroughly later using a slit lamp.
Refractive error determination-Refraction
The examiner will determine the refractive error
and obtain a prescription for corrective lenses for
people whose visual acuity is less than 20/20. An
instrument called a phoropter, which the patient
sits behind, is generally used (sometimes the refraction can be done with a trial frame that the patient
wears). The phoropter is equipped with many lenses
that allow the examiner to test many combinations of
corrections to learn which correction allows the
patient to see the eye chart most clearly. This is the
part of the exam when the doctor usually says,
‘‘Which is better, one or two?’’ The phoropter also
contains prisms, and sometimes the doctor will intentionally make the patient see double. This may help
in determining a slight eye turn. The exam will check
vision at distance and near (reading).
A prescription for corrective lenses can also be
supplied by automated refracting devices, which measure the necessary refraction by shining a light into the
eye and observing the reflected light. Another objective way to obtain a prescription is using a hand-held
retinoscope. As in the automated method just mentioned, the doctor shines a light in the patient’s eyes
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Eye examination

medications, antibiotics, and birth control pills), any
blood relatives with eye disorders, and any systemic
disorders the patient may have. The patient should
also tell the doctor about hobbies and work conditions. This information helps in modifying prescriptions and lets the doctor know how the patient uses his
or her eyes. For example, using a computer screen vs.
construction work, the working distance of a computer screen may affect the prescription; the construction
worker needs protective eyewear.

Eye examination

check the pressure of the eyes. A colored eyedrop
may be instilled immediately prior to this test.
The drop has a local anesthetic so the patient
won’t feel the probe touch the eye. It is a quick
procedure.
Visual field measurement

A woman looking through a refractor. (Photograph by John
Greim, Photo Researchers. Reproduced by permission.)

and can determine an objective prescription. This is
helpful in young children or infants.
Sometimes drops will be instilled in the patient’s
eyes before this part of the exam. The drops may relax
accommodation so that the refraction will be more
accurate. This is helpful in children and people who
are farsighted.
After the refraction and other visual status tests,
for example color tests or binocularity tests (can the
patient see 3-D, or have depth perception), the doctor
will check the health of the eyes and surrounding
areas. The main instruments used are the ophthalmoscope and the slit lamp.
Ophthalmoscopic examination
These observations are best accomplished after
dilating the pupils and require an ophthalmoscope.
The ophthalmoscope most frequently used is a called
a direct ophthalmoscope. It is a hand-held illuminated
15X multi-lens magnifier that lets the examiner view
the inside back area of the eye (fundus). The retina,
blood vessels, optic nerve, and other structures are
examined.
Slit lamp examination
The slit lamp is a microscope with a light
source that can be adjusted. This magnifies the
external and some internal structures of the eyes.
The lid and lid margin, cornea, iris, pupil, conjunctiva, sclera, and lens are examined. The slit lamp is
also used in contact lens evaluations. A little probe
called a tonometer may be used at this time to
1410

A perimeter, the instrument for measuring visual
fields, is a hollow hemisphere, equipped with a light
source that projects dots of light over the inside surface. The patient’s head is positioned so that the eye
being tested is at the center of the sphere and (about
13 in. 33 cm) from all points on the inside surface of
the hemisphere. The patient stares straight ahead at
an image on the center of the surface and signals
whenever he or she detects a flash of light. The perimeter records which flashes are seen and which are
missed and maps the patient’s field of vision and
blindspots.
Intraocular pressure (IOP) measurement
Tonometers are used to measure IOP. Some tonometers measure pressure by expelling a puff of air
(noncontact tonometer) towards the eyeball from a
very short distance. Other tonometers are placed
directly on the cornea. The noncontact tonometers
are not as accurate as the contact tonometers and are
sometimes used for screenings.
Completing the evaluation with additional tests
Depending upon the results other tests may be necessary. These can include, but are not limited to binocular
indirect ophthalmoscopy, gonioscopy, color tests, contrast sensitivity testing, ultasonography, and others. The
patient may have to return for additional visits.

Results
External observations
INITIAL OBSERVATIONS AND SLIT LAMP EXAM. Some
general observations the doctor may be looking for
include: head tilt; drooping eyelids (ptosis); eye turns;
red eyes (injection); eye movement; size, shape, and
color of the iris; clarity of the cornea, anterior chamber, and lens. The anterior chamber lies behind the
cornea and in front of the iris. If it appears cloudy or
if cells can be seen in it during the slit lamp exam
an inflammation may be present. A narrow anterior
chamber may put the patient at risk for glaucoma.
A clouding of the normally clear lens is called a
cataract.

GALE ENCYCLOPEDIA OF MEDICINE

Amblyopia—Decreased visual acuity, usually in one
eye, in the absence of any structural abnormality in
the eye.
Conjunctiva—The mucous membrane that covers the
white part of the eyes (sclera) and lines the eyelids.
Cornea—Clear outer covering of the front of the eye.
Floaters—Translucent specks that float across the
visual field, due to small objects floating in the vitreous humor.
Fundus—The inside of an organ. In the eye, refers to the
back area that can be seen with the ophthalmoscope.
Glaucoma—There are many types of glaucoma.
Glaucoma results in optic nerve damage and a
decreased visual field and blindness if not treated. It
is usually associated with increased IOP, but that is
not always the case. The three factors associated with
glaucoma are increased IOP, a change in the optic
nerve head, and changes in the visual field.
Gonioscope—An instrument used to inspect the eye
(e.g., the anterior chamber). It consists of a magnifier
and a lens equipped with mirrors; it’s placed on the
patient’s cornea.
Iris—The colored ring just behind the cornea and in
front of the lens that controls the amount of light sent
to the retina.

Internal observations
observations
include, but are not limited to the retina, blood vessels, and optic nerve. The optic nerve enters the back
of the eye and can be checked for swelling or other
problems. The blood vessels can be viewed as can the
retina. The macula is a 3–5 mm area in the back of
the eye and is responsible for central vision. The
fovea is a small area located within the macula and
is responsible for sharp vision. When a person looks
at something, they are pointing the fovea at the
object. Changes in the macular area can be observed
with the ophthalmoscope. Retinal tears or detachments can also be seen.
OPHTHALMOSCOPIC

EXAM. The

Visual ability
VISUAL ACUITY. The refraction will determine the

refractive status for each eye for distance and for near.
A prescription for glasses is made after taking many
things into consideration. The eye doctor may alter a
GALE ENCYCLOPEDIA OF MEDICINE

Macula—The central part of the retina where the rods
and cones are densest.
Ophthalmoscope—An instrument designed to view
structures in the back of the eye.
Optic nerve—The nerve that carries visual messages
from the retina to the brain.
Pupil—The circular opening that looks like a black
hole in the middle of the iris.
Retina—The inner, light-sensitive layer of the eye
containing rods and cones; transforms the image it
receives into electrical messages which are then sent
to the brain via the optic nerve.
Sclera—The tough, fibrous, white outer protective
covering that surrounds the eye.
Slit lamp—A microscope that projects a linear slit
beam of light onto the eye; allows viewing of the
conjunctiva, cornea, iris, aqueous humor, lens, and
eyelid.
Tonometer—An instrument that measures intraocular pressure (IOP).
Ultrasonography—A method of obtaining structural
information about internal tissues and organs where
an image is produced because different tissues
bounce back ultrasonic waves differently.

prescription based upon many factors. Different materials for glasses may be suggested. For example, polycarbonate may be suggested for children or people
active in sports because it is very impact resistant.
Bifocals, trifocals, single-vision spectacles, and contact lenses are also options.
VISUAL FIELDS. A normal visual field extends
about 608 upward, about 758 downward, about 658
toward the nose, and about 1008 toward the ear and
has one blind spot close to the center. Defects in the
visual field signify damage to the retina, optic nerve, or
the neurological visual pathway.

Seeing clearly does not necessarily mean the eyes
are healthy or that the eyes are working together as a
team. Regular checkups can detect abnormalities,
hopefully before a problem arises. The eye doctor
can suggest ways to help protect the eyes and vision
(e.g., safety goggles, ultraviolet (UV) coatings on
lenses). A person should also have an eye exam if
they notice a change in vision, eyestrain, blur, flashes
of light, a sudden onset of floaters (little dots),
1411

Eye examination

KEY TERMS

Eye glasses and contact lenses

distortion of objects, double vision, redness, pain or
discharge.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
PO Box 7424, San Francisco, CA 94120-7424. <http://
www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.

Lorraine Lica, PhD

Eye exercises see Vision training

required to wear safety eyewear over the contact
lenses. Some occupations, such as construction or
auto repair, may require safety lenses and safety
frames. Physicians and employers should be consulted
for recommendations.

Description
Eyes are examined by optometrists (O.D.) or by
ophthalmologists (M.D. or D.O.—doctor of osteopathy). Prescriptions, if necessary, are then given to
patients for glasses. The glasses are generally made
by an optician. A separate contact lens-fitting exam
is necessary if the patient wants contact lenses, because
an eyeglass prescription is not the same as a contact
lens prescription.
Eyeglasses

Eye glasses and contact lenses
Definition
Eyeglasses and contact lenses are devices that correct refractive errors in vision. Eyeglass lenses are
mounted in frames worn on the face, sitting mostly
on the ears and nose, so that the lenses are positioned
in front of the eyes. Contact lenses appear to be worn
in direct contact with the cornea, but they actually
float on a layer of tears that separates them from the
cornea.

Purpose
The purpose of eyeglasses and contact lenses is to
correct or improve the vision of people with nearsightedness (myopia), farsightedness (hyperopia), presbyopia, and astigmatism.

Precautions
People allergic to certain plastics should not
wear contact lenses or eyeglass frames or lenses manufactured from that type of plastic. People allergic to
nickel should not wear Flexon frames. People at risk
of being in accidents that might shatter glass lenses
should wear plastic lenses, preferably polycarbonate.
(Lenses made from polycarbonate, the same type of
plastic used for the space shuttle windshield, are
about 50 times stronger than other lens materials.)
Also, people at risk of receiving electric shock should
avoid metal frames.
People employed in certain occupations may be
prohibited from wearing contact lenses, or may be
1412

More than 140 million people in the United States
wear eyeglasses. People whose eyes have refractive
errors do not see clearly without glasses, because the
light emitted from the objects they are observing does
not come into focus on their retinas. For people who
are farsighted, images come into focus behind the
retina; for people who are nearsighted, images come
into focus in front of the retina.
LENSES. Lenses work by changing the direction of
light so that images come into focus on the retina. The
greater the index of refraction of the lens material and
the greater the difference in the curvature between the
two surfaces of the lens, the greater the change in
direction of light that passes through it, and the
greater the correction.

Lenses can be unifocal, with one correction for all
distances, or they can be correct for more than one
distance (multifocal). One type of multifocal, the bifocal, has an area of the lens (usually at the bottom) that
corrects for nearby objects (about 14 in from the eyes);
the remainder of the lens corrects for distant objects
(about 20 ft from the eyes). Another type of multifocal, a trifocal, has an area in-between that corrects
for intermediate distances (usually about 28 in).
Conventional bifocals and trifocals have visible lines
between the areas of different correction; however,
lenses where the correction gradually changes from
one area to the other, without visible lines, have been
available since the 1970s. Such lenses are sometimes
called progressives or no-line bifocals.
To be suitable for eyeglass lenses, a material must be
transparent, without bubbles, and have a high index of
refraction. The greater the index of refraction, the thinner the lens can be. Lenses are made from either glass or
GALE ENCYCLOPEDIA OF MEDICINE

Glass was the first material to be used for eyeglass
lenses, and was used for several hundred years before
plastic was introduced.
Optical-quality acrylic was introduced for eyeglass use in the early 1940s, but because it was easily
scratched, brittle, and discolored rapidly, it did
not supplant glass as the material of choice.
Furthermore, it wasn’t suitable for people with large
refractive errors. A plastic called CR-39, introduced in
the 1960s, was more suitable. Today, eyeglass wearers
can also choose between polycarbonate, which is the
most impact-resistant material available for eyewear,
and polyurethane, which has exceptional optical qualities and higher refraction than the conventional plastics even glass. Patients with high prescriptions should
ask about high index material options for their lenses.
Aspheric lenses are also useful for high prescriptions.
They are flatter and lighter than conventional lenses.
There are many lenses and lens-coating options
for individual needs, including coatings that block the
ultraviolet (UV) light or UV and blue light, which
have been found to be harmful to the eyes. Such coatings are not needed on polycarbonate lenses, which
already have UV protection. UV coatings are particularly important on sunglasses and ski goggles.
Sunglasses, when nonprescription, should be labeled
with an indication that they block out 99–100% of
both UV-A and UV-B rays.
There are anti-scratch coatings that increase the
surface hardness of lenses (an important feature when
using plastic lenses) and anti-reflective (AR) coatings
that eliminate almost all glare and allow other people
to see the eyes of the wearer. AR coatings may be
particularly helpful to people who use computers or
who drive at night. Mirror coatings that prevent other
people from seeing the wearer’s eyes are also available.
There is a whole spectrum of tints, from light tints to
darker tints, used in sunglasses. Tint, however, does
not block out UV rays, so a UV coating is needed.
Polaroid lenses that block out much of the reflected
light also allow better vision in sunny weather and are
helpful for people who enjoy boating. Photosensitive
(photochromatic) lenses that darken in the presence of
bright light are handy for people who don’t want to
carry an extra set of glasses. Photochromatic lenses are
available in glass and plastic.
FRAMES. Frames can be made from metal or plastic, and they can be rimless. There is an almost

GALE ENCYCLOPEDIA OF MEDICINE

unlimited variety of shapes, colors, and sizes. The
type and degree of refractive correction in the lens
determine to some extent the type of frame most suitable. Some lenses are too thick to fit in metal rims,
and some large-correction prescriptions are best suited
to frames with small-area lenses.
Rimless frames are the least noticeable type, and
they are lightweight because the nosepiece and temples
are attached directly to the lenses, eliminating the
weight of the rims. They tend to not be as sturdy as
frames with rims, so they are not a good choice for
people who frequently remove their glasses and put
them on again. They are also not very suitable for
lenses that correct a high degree of farsightedness,
because such lenses are thin at the edges.
Metal frames are less noticeable than plastic, and
they are lightweight. They are available in solid gold,
gold-filled, anodized aluminum, nickel, silver, stainless steel, and now titanium and titanium alloy. Until
the late 1980s, when titanium-nickel alloy and titanium frames were introduced, metal frames were, in
general, more fragile than plastic frames. The titanium
frames, however, are very strong and lightweight. An
alloy of titanium and nickel, called Flexon, is not only
strong and lightweight, but returns to its original
shape after being twisted or dented. It is not perfect
for everyone, though, because some people are sensitive to its nickel. Flexon frames are also relatively
expensive.
Plastic frames are durable, can accommodate just
about any lens prescription, and are available in a wide
range of prices. They are also offered in a variety of
plastics (including acrylic, epoxy, cellulose acetate,
cellulose propionate, polyamide, and nylon) and in
different colors, shapes, and levels of resistance to
breakage. Epoxy frames are resilient and return to
their original shape after being deformed, so they do
not need to be adjusted as frequently as other types.
Nylon frames are almost unbreakable. They revert to
their original shape after extreme trauma and distortion; because of this property, though, they cannot be
readjusted after they are manufactured.
FIT. The patient should have the distance between
the eyes (PD) measured, so that the optical centers of
the lenses will be in front of the patient’s pupils.
Bifocal heights also have to be measured with the
chosen frame in place and adjusted on the patient.
Again, this is so the lenses will be positioned correctly.
If not positioned correctly, the patient may experience
eyestrain or other problems. This can occur with overthe-counter reading glasses. The distance between the
lenses is for a ‘‘standard’’ person. Generally, this will

1413

Eye glasses and contact lenses

plastic (hard resin). The advantage of plastic is that it is
lightweight and more impact resistant than glass. The
advantage of glass is that it is scratch resistant and
provides the clearest possible vision.

Eye glasses and contact lenses

not be a problem, but if a patient is sensitive or has
more closely set eyes, for example, it may pose a
problem. Persons buying ready-made sunglasses or
reading glasses should hold them up to see if they
appear clear. They should also hold the lenses to see
an object with straight lines reflected off of the lenses.
If the lines don’t appear straight, the lenses may be
warped or inferior.
Patients may sometimes need a few days to adjust
to a new prescription; however, problems should be
reported, because the glasses may need to be
rechecked.
Contact lenses
More than 32 million people in the United States
wear these small lenses that fit on top of the cornea.
They provide a field of view unobstructed by eyeglass
frames; they do not fog up or get splattered, so it is
possible to see well while walking in the rain; and they
are less noticeable than any eyeglass style. On the
other hand, they take time to get accustomed to;
require more measurements for fitting; require many
follow-up visits to the eye doctor; can lead to complications such as infections and corneal damage; and
may not correct astigmatism as well as eyeglasses,
especially if the astigmatism is severe.
Originally, hard contact lenses were made of a
material called PMMA. Although still available, the
more common types of contact lenses are listed below:


Rigid gas-permeable (RGP) daily-wear lenses are
made of plastic that does not absorb water but allows
oxygen to get from the atmosphere to the cornea.
(This is important because the cornea has no blood
supply and needs to get its oxygen from the atmosphere through the film of tears that moves beneath
the lens.) They must be removed and cleaned each
night.



Rigid gas-permeable (RGP) extended-wear lenses
are made from plastic that also does not absorb
water but is more permeable to oxygen than the
plastic used for daily-wear lenses. They can be worn
up to a week.



Daily wear soft lenses are made of plastic that is
permeable to oxygen and absorbs water; therefore,
they are soft and flexible. These lenses must be
removed and cleaned each night, and they do not
correct all vision problems. Soft lenses are easier to
get used to than rigid lenses, but are more prone to
tears and do not last as long.



Extended-wear soft lenses are highly permeable to
oxygen, are flexible by virtue of their ability to

1414

absorb water, and can usually be worn for up to
one week. They do not correct all vision problems.
There is more of a risk of infection with extendedwear lenses than with daily-wear lenses.


Extended-wear disposable lenses are soft lenses worn
continually for up to six days and then discarded,
with no need for cleaning.



Planned-replacement soft lenses are daily wear lenses
that are replaced on a regular schedule, which is
usually every two weeks, monthly, or quarterly.
They must also be cleaned.

Soft contact lenses come in a variety of materials.
There are also different kinds of RGP and soft multifocal contact lenses available. Monovision, where one
contact lens corrects for distance vision while the other
corrects for near vision, may be an option for presbyopic patients. Monovision, however, may affect
depth perception and may not be appropriate for
everyone. Contact lenses also come in a variety of
tints. Soft contacts are available that can make eyes
appear a different color. Even though such lenses have
no prescription, they must still be fitted and checked to
make sure that an eye infection does not occur. People
should never wear someone else’s contact lenses. This
can lead to infection or damage to the eye.
Tiny, surgically implanted contact lenses may one
day replace eyeglasses, contact lenses and laser surgery
for some patients with extreme nearsightedness.
Called intraocular lenses, they were still investigational in the spring of 2004, and although they are
surgically installed, they can be removed.
Researchers expected FDA approval in 2004.

Aftercare
Contact lens wearers must be examined periodically by their eye doctors to make sure that the lenses
fit properly and that there is no infection. Infection
and lenses that do not fit properly can damage the
cornea. Patients can be allergic to certain solutions
that are used to clean or lubricate the lenses. For that
reason, patients should not randomly switch products
without speaking with their doctor. Contact lens wearers should seek immediate attention if they experience
eye pain, a burning sensation, red eyes, intolerable
sensitivity to light, cloudy vision, or an inability to
keep the eyes open.
To avoid infection, it is important for contact lens
wearers to exactly follow their instructions for lens
insertion and removal, as well as cleaning. Soft contact
lens wearers should never use tap water to rinse their
lenses or to make up solutions. All contact lens
GALE ENCYCLOPEDIA OF MEDICINE

Astigmatism—Assymetric vision defects due to
irregularities in the cornea.
Cornea—The clear outer covering of the front of
the eye.
Index of refraction—A constant number for any
material for any given color of light that is an indicator of the degree of the bending of the light
caused by that material.
Lens—A device that bends light waves.
Permeable—Capable of allowing substances to
pass through.
Polycarbonate—A very strong type of plastic often
used in safety glasses, sport glasses, and children’s
eyeglasses. Polycarbonate lenses have approximately 50 times the impact resistance of glass
lenses.
Polymer—A substance formed by joining smaller
molecules. For example, plastic, acrylic, cellulose
acetate, cellulose propionate, nylon, etc.
Presbyopia—A condition affecting people over the
age of 40 where the system of accommodation that
allows focusing of near objects fails to work
because of age-related hardening of the lens of
the eye.

2004 claims to achieve exceptional vision assessment
and 20/10 acuity by using wavefront measurements
and precise parameters to produce measurements
such as pupil size and distance, along with other customized lens and frame features.
Resources
PERIODICALS

Asp, Karen. ‘‘Implanted Contact Lenses.’’ Prevention (June
2004): 68.
‘‘Patent Issued for Z-lens Wavefront Guided, Customized
Eyeglasses.’’ Medical Devices & Surgical Technology
Week (April 18, 2004): 150.
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
PO Box 7424, San Francisco, CA 94120-7424. <http://
www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
Optician Association of America. 7023 Little River
Turnpike, Suite 207, Annandale, VA 22003. (703) 9168856. <http://www.opticians.org>.
OTHER

Contact Lens Council. <http://
www.contactlenscouncil.org>.

Lorraine Lica, PhD
Teresa G. Odle

Retina—The inner, light-sensitive layer of the eye
containing rods and cones; transforms the image it
receives into electrical messages sent to the brain
via the optic nerve.
Ultraviolet (UV) light—Part of the electromagnetic
spectrum with a wavelength just below that of visible light. It is damaging to living material, especially eyes and DNA.

Eye muscle surgery
Definition

wearers should also always have a pair of glasses and a
carrying case for their contacts with them, in case the
contacts have to be removed due to eye irritation.

Eye muscle surgery is surgery to weaken,
strengthen, or reposition any of the muscles that
move the eyeball (the extraocular muscles).

Purpose
Risks
Wearing contact lenses increases the risk of corneal damage and eye infections.

Normal results
The normal expectation is that people will achieve
20/20 vision while wearing corrective lenses. A new
technology for customized eyeglasses patented in
GALE ENCYCLOPEDIA OF MEDICINE

The purpose of eye muscle surgery is generally to
align the pair of eyes so that they gaze in the same
direction and move together as a team, either to
improve appearance or to aid in the development of
binocular vision in a young child. To achieve binocular vision, the goal is to align the eyes so that the
location of the image on the retina of one eye corresponds to the location of the image on the retina of the
other eye.
1415

Eye muscle surgery

KEY TERMS

Eye muscle surgery

In addition, sometimes eye muscle surgery can
help people with other eye disorders (nystagmus and
Duane syndrome, for example).

Precautions
Depth perception (stereopsis) develops around
the age of three months old. For successful development of binocular vision and the ability to perceive
three-dimensionally, the surgery should not be postponed past the age of four. The earlier the surgery the
better the outcome, so an early diagnosis is important.
Surgery may even be performed before two years old.
After surgery, if binocular vision is to develop, corrective lenses and eye exercises (vision therapy) will probably be necessary.

Description
The extraocular muscles attach via tendons to the
sclera (the white, opaque, outer protective covering of
the eyeball) at different places just behind an imaginary equator circling the top, bottom, left, and right of
the eye. The other end of each of these muscles
attaches to a part of the orbit (the eye socket in the
skull). These muscles enable the eyes to move up,
down, to one side or the other, or any angle in
between.
Normally both eyes move together, receive the
same image on corresponding locations on both retinas, and the brain fuses these images into one threedimensional image. The exception is in strabismus
which is a disorder where one or both eyes deviate
out of alignment, most often outwardly (exotropia)
or toward the nose (esotropia). The brain now receives
two different images, and either suppresses one or the
person sees double (diplopia). This deviation can be
adjusted by weakening or strengthening the appropriate muscles to move the eyes toward the center. For
example, if an eye turns upward, the muscle at the
bottom of the eye could be strengthened.
Rarely, eye muscle surgery is performed on people
with nystagmus or Duane syndrome. Nystagmus is a
condition where one or both eyes move rapidly or
oscillate; it can sometimes be helped by moving the
eyes to the position of least oscillation. Duane syndrome is a disorder where there is limited horizontal
eye movement; it can sometimes be relieved by surgery
to weaken an eye muscle.
There are two methods to alter extraocular muscles. Traditional surgery can be used to strengthen,
weaken, or reposition an extraocular muscle. The surgeon first makes an incision in the conjunctiva (the
1416

clear membrane covering the sclera), then puts a
suture into the muscle to prevent it from getting lost
and loosens the muscle from the eyeball with a surgical
hook. During a resection, the muscle is detached from
the sclera, a piece of muscle is removed so the muscle is
now shorter, and the muscle is reattached to the same
place. This strengths the muscle. In a recession, the
muscle is made weaker by repositioning it. More than
one extraocular eye muscle might be operated on at
the same time.
Another way of weakening eye muscles, using
botulinum toxin injected into the muscle, was introduced in the early 1980s. Although the botulinum
toxin wears off, the realignment may be permanent,
depending upon whether neurological connections for
binocular vision were established during the time the
toxin was active. This technique can also be used to
adjust a muscle after traditional surgery.
The cost of eye muscle surgery is about $2,000–
$4,000, and about 700,000 surgeries are performed
annually in the United States.

Preparation
Patients should make sure their doctors are aware
of any medications that they are taking, even over-thecounter medications. Patients should not take aspirin,
or any other blood-thinning medications for ten days
prior to surgery, and should not eat or drink after
midnight the night before.

Aftercare
Patients will need someone to drive them home
after their surgery. They should continue to avoid
aspirin and other non-steroidal anti-inflammatory
agents for an additional three days, but they can take
acetaminophen (e.g., Tylenol). Patients should discuss
this with the surgeon to be clear what medications they
can or cannot take. Pain will subside after two to three
days, and patients can resume most normal activities
within a few days. Again, this may vary with the
patient and the patient should discuss returning to
normal activity with the surgeon. They should not
get their eyes wet for three to four days and should
refrain from swimming for 10 days. Operated eyes will
be red for about two weeks.

Risks
As with any surgery, there are risks involved. Eye
muscle surgery is relatively safe, but very rarely a cut
muscle gets lost and can not be retrieved. This, and
GALE ENCYCLOPEDIA OF MEDICINE

American Academy of Pediatric Ophthalmology and
Strabismus (AAPOS). <http://med-aapos.bu.edu>.
OTHER

Botulinum toxin (botulin)—A neurotoxin made by
Clostridium botulinum; causes paralysis in high
doses, but is used medically in small, localized
doses to treat disorders associated with involuntary
muscle contraction and spasms, in addition to
strabismus.
Conjunctiva—The mucous membrane that covers
the eyes and lines the eyelids.
Extraocular muscles—The muscles (lateral rectus,
medial rectus, inferior rectus, superior rectus,
superior oblique, and inferior oblique) that move
the eyeball.
Orbit—The cavity in the skull containing the eyeball; formed from seven bones: frontal, maxillary,
sphenoid, lacrimal, zygomatic, ethmoid, and
palatine.
Retina—The inner, light-sensitive layer of the eye
containing rods and cones; transforms the image it
receives into electrical messages sent to the brain
via the optic nerve.
Sclera—The tough, fibrous, white outer protective
covering of the eyeball.
Strabismus—A disorder where the two eyes do not
point in the same direction.

other serious reactions, including those caused by
anesthetics, can result in vision loss in the affected
eye. Occasionally, retinal or nerve damage occurs.
Double vision is not uncommon after eye muscle surgery. As mentioned earlier, glasses or vision therapy
may be necessary.

Normal results
Cosmetic improvement is likely with success rate
estimates varying from about 65–85%. According to
the best statistics as of 1998, binocular vision is
improved in young children about 35% of the time.
There is no improvement, or the condition worsens
15–35% of the time. A second operation may rectify
less-than-perfect outcomes.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
PO Box 7424, San Francisco, CA 94120-7424. <http://
www.eyenet.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Olitsky, Scott E., and Leonard B. Nelson. Strabismus
WebBook. May 4, 1998. <http://www.smbs.buffalo.
edu/oph/ped/webbook.htm>.

Lorraine Lica, PhD

Eye training see Vision training

Eyelid disorders
Definition
An eyelid disorder is any abnormal condition that
affects the eyelids.

Description
Eyelids consist of thin folds of skin, muscle, and
connective tissue. The eyelids protect the eyes and
spread tears over the front of the eyes. The inside of
the eyelids are lined with the conjunctiva of the eyelid
(the palpebral conjunctiva), and the outside of the lids
are covered with the body’s thinnest skin. Some common lid problems include the following: stye, blepharitis, chalazion, entropion, ectropion, eyelid edema, and
eyelid tumors.
Stye
A stye is an infection of one of the three types of
eyelid glands near the lid margins, at the base of the
lashes.
Chalazion
A chalazion is an enlargement of a meibomian
gland (an oil-producing gland in the eyelid), usually
not associated with an infectious agent. More likely,
the gland opening is clogged. Initially, a chalazion may
resemble a stye, but it usually grows larger. A chalazion may also be located in the middle of the lid and be
internal.
Blepharitis
Blepharitis is the inflammation of the eyelid margins, often with scales and crust. It can lead to eyelash
loss, chalazia, styes, ectropion, corneal damage, excessive tearing, and chronic conjunctivitis.
1417

Eyelid disorders

KEY TERMS

Eyelid disorders

Entropion
Entropion is a condition where the eyelid margin
(usually the lower one) is turned inward; the eyelashes
touch the eye and irritate the cornea.
Ectropion
Ectropion is a condition where one or both eyelid
margins turn outward, exposing both the conjunctiva
that covers the eye and the conjunctiva that lines the
eyelid.
Eyelid edema
Eyelid edema is a condition where the eyelids
contain excessive fluid.
Eyelid tumors
Eyelids are susceptible to the same skin tumors as
the skin over the rest of the body, including noncancerous tumors and cancerous tumors (basal cell carcinoma, squamous cell carcinoma, malignant melanoma,
and sebaceous gland carcinoma). Eyelid muscles are
susceptible to sarcoma.

Causes and symptoms
Stye
Styes are usually caused by bacterial staphylococcal
infections. The symptoms are pain and inflammation in
one or more localized regions near the eyelid margin.
Chalazion
A chalazion is caused by a blockage in the outflow
duct of a meibomian gland. Symptoms are inflammation and swelling in the form of a round lump in the lid
that may be painful.
Blepharitis
Some cases of blepharitis are caused by bacterial
infection and some by head lice, but in some cases, the
cause is unclear. It may also be caused by an overproduction of oil by the meibomian glands.
Blepharitis can be a chronic condition that begins in
early childhood and can last throughout life.
Symptoms can include itching, burning, a feeling that
something is in the eye, inflammation, and scales or
matted, hard crusts surrounding the eyelashes.
Entropion
Entropion usually results from aging, but sometimes can be due to a congenital defect, a spastic eyelid
1418

A chalazion on the eyelid. This condition is caused by an
obstruction of one of the meibomian glands which lubricate
the edge of the eyelid. (Photo Researchers, Inc. Reproduced by
permission.)

muscle, or a scar on the inside of the lid from surgery,
injury, or disease. It is accompanied by excessive tearing, redness, and discomfort.
Ectropion
Similar to entropion, the usual cause of ectropion
is aging. It also can be due to a spastic eyelid muscle or
a scar, as in entropion. It also can be the result of
allergies. Symptoms are excessive tearing and hardening of the eyelid conjunctiva.
Eyelid edema
Eyelid edema is most often caused by allergic
reactions, for example, allergies to eye makeup, eyedrops or other drugs, or plant allergens such as pollen.
Trichinosis, a disease caused by eating undercooked
meat, also causes eyelid edema. However, swelling can
also be caused by more serious causes, such as infection, and can lead to orbital cellulitis which can threaten vision. Symptoms can include swelling, itching,
redness, or pain.
Eyelid tumors
Tumors found on the eyelids are caused by the
same conditions that cause these tumors elsewhere on
the body. They are usually painless and may or may
not be pigmented. Some possible causes include AIDS
(Kaposi’s sarcoma) or increased exposure to ultraviolet
(UV) rays which may lead to skin cancer.

Diagnosis
An instrument called a slit lamp is generally used
to magnify the structures of the eyes. The doctor may
GALE ENCYCLOPEDIA OF MEDICINE

Entropion and ectropion

A close-up of the eye of an elderly patient showing ectropion
of the lower eyelid. Ectropion is a condition in which the eyelid
turns away from the eye. The most common type is senile
ectropion (seen here), in which the droop of the eyelid is due
to loss of tissue elasticity in old age and weakness in the
muscles surrounding the eye. (Photograph by Dr. P. Marazzi,
Photo Researchers, Inc. Reproduced by permission.)

press on the lid margin to see if oil can be expressed
from the meibomian glands. The doctor may invert
the lid to see the inside of the lid. Biopsy is used to
diagnose cancerous tumors.

Treatment
Stye
Styes are treated with warm compresses for 10–15
minutes, three to four times a day. Chloramphenicol
ointment may be used as well. Sometimes topical antibiotics may be prescribed if the infection is spreading.

Both entropion and ectropion can be surgically
corrected. Prior to surgery, the lower lid of entropion
can be taped down to keep the lashes off the eye, and
both can be treated with lubricating drops to keep the
cornea moist.
Eyelid edema
Patients with swollen eyelids should contact their
eye doctor. A severely swollen lid can press on the eye
and possibly increase the intraocular pressure. An
infection needs to be ruled out. Or, something as simple as an allergy to nail polish and then touching the
eyes can cause swelling. The best treatment for allergic
eyelid edema is to find and remove the substance
causing the allergy. When that is not possible, as in
the case of plant allergens, cold compresses and immunosuppresesive drugs such as corticosteroid creams
are helpful. However, steroids can cause cataracts
and increase intraocular pressure and patients must
be very careful not to get the cream in their eyes. This
should not be done unless under a doctor’s care. For
edema caused by trichinosis, the trichinosis must be
treated.

Chalazion
About 25% of chalazia will disappear spontaneously, but warm compresses may speed the process.
Chloramphenicol ointment may be used as well.
Because chalazia are inside the lid, topical medications
are generally of no benefit. Medication may need to be
injected by the doctor into the chalazion or if that
doesn’t help the chalazion may need to be excised. If
what appears to be a chalazion recurs on the same site
as any previous one, the possibility of sebaceous gland
carcinoma should be investigated by biopsy.
Blepharitis
Blepharitis is treated with hot compresses, with
antibiotic ointment, and by cleaning the eyelids with a
moist washcloth and then with baby shampoo. Good
hygiene is essential. Patients can try to keep rooms
dry, such as by placing a bowl of water on top of a
GALE ENCYCLOPEDIA OF MEDICINE

Eyelid tumors
Cancerous tumors should be removed upon discovery, and noncancerous tumors should be removed
before they become big enough to interfere with vision
or eyelid function. Eyelid tumors require special consideration because of their sensitive location. It is
important that treatment not compromise vision, eye
movement, or eyelid movement. Accordingly, eyelid
reconstruction will sometimes accompany tumor
excision.

Prognosis
The prognosis for styes and chalazia is good to
excellent. With treatment, blepharitis, ectropion, and
entropion usually have good outcomes. The prognosis
for nonmalignant tumors, basal cell carcinoma, and
squamous cell carcinoma is good once they are
1419

Eyelid disorders

radiator. Tear film supplements such as hypromellose
can help moisten the eyes when dry. If itching, soreness, or redness occurs from the tear film drops, they
should be stopped. Topical or systemic antibiotics also
may be prescribed. If the blepharitis doesn’t clear up
with treatment or if it seems to be a chronic problem,
the patient may have acne rosacea. These patients may
need to see a dermatologist as well.

Eyelid disorders

KEY TERMS

sulfide to kill the bacteria helps control the blepharitis.
When using anything near the eyes, it is important to
read the label or consult with a doctor first.

Allergen—A substance capable of inducing an
allergic response.
Allergic reaction—An immune system reaction to
a substance in the environment; symptoms include
rash, inflammation, sneezing, itchy watery eyes,
and runny nose.

Avoiding allergens helps prevent allergic eyelid
edema. Staying inside as much as possible when pollen
counts are high and eliminating the use of, or at least
removing eye makeup thoroughly, or using hypoallergenic makeup may help if the person is sensitive
to those substances.

Conjunctiva—The mucous membrane that covers
the white part of the eyes and lines the eyelids.

Sunscreen, UV-blocking sunglasses, and wide
brimmed hats can help prevent eyelid tumors.

Edema—A condition where tissues contain excessive fluid.

Entropian
unpreventable.

Meibomian gland—Oil-producing glands in the
eyelids that open near the eyelid margins.

Resources

and

ectropian

seem

to

be

PERIODICALS

properly removed. Survival rate for malignant melanoma depends upon how early it was discovered and if
it was completely removed. Sebaceous carcinomas are
difficult to detect, so poor outcomes are more
frequent.
All of these eyelid disorders, if not treated, can
lead to other, possibly serious vision problems—dry
eye, astigmatism, or even vision loss, for example. An
ophthalmologist or optometrist should be consulted.

Prevention
Good lid hygiene is very important. Regular eyelid washing with baby shampoo helps prevent styes,
chalazia, blepharitis, and eyelid edema. To avoid these
problems, it’s also important to refrain from touching
and rubbing the eyes and eyelids, especially with hands
that have not just been washed.
Blepharitis is associated with dandruff, which is
caused by a kind of bacteria that is one of the causes
of blepharitis. Controlling dandruff by washing the hair,
scalp, and eyebrows with shampoo containing selenium

1420

‘‘At a Glance: Chalazion Versus Stye.’’ GP May 3, 2004: 52.
‘‘Practical Ophthalmology for GPs: The Treatment of
Blepharitis.’’ Pulse (May 10, 2004): 60.
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
PO Box 7424, San Francisco, CA 94120-7424. <http://
www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
American Society of Ophthalmic Plastic and Reconstructive
Surgery. 1133 West Morse Blvd, #201, Winter Park, FL
32789. (407) 647-8839. <http://www.asoprs.org>.
OTHER

‘‘Eyelid Abnormalities.’’ Eye Clinic of Fairbanks. <http://
www.eyeclinicfbks.com/ECFLID.htm>.
RxMed. <http://www.rxmed.com>.

Lorraine Lica, PhD
Teresa G. Odle

Eyelid edema see Eyelid disorders
Eyelid plastic surgery see Blepharoplasty

GALE ENCYCLOPEDIA OF MEDICINE

F
Fabry’s disease see Lipidoses

blood below the skin, is the most frequent complication of face lift surgery.

Description

Face lift
Definition
Face lift surgery is a cosmetic procedure that involves
redirecting some of the skin and muscle tissue of the face
and neck to counter signs of aging produced by gravity.

Purpose
The purpose of face lift surgery, also known as
facialplasty, rhytidoplasty, or cervicofacial rhytidectomy, is to improve the appearance of the face by
repositioning the skin and tightening some of the underlying muscle and tissue. The procedure is designed to
counter sagging and looseness in skin and muscle
tissue caused by gravity as the patient ages. Face lift
surgery will not erase all facial wrinkles, as the term
rhytidectomy (which literally means ‘‘surgical removal
of wrinkles’’) might imply. Wrinkles around the mouth
and eyes, for example, may benefit little from face lift
surgery. Other procedures, such as blepharoplasty,
chemical peel, or dermabrasion, also may be necessary.

Precautions
Patients with other medical conditions should
consult with their primary physician before undergoing face lift surgery. Lung problems, heart disease, and certain other conditions can lead to a
higher risk of complications. Patients who take
medications that can alter the way their blood
clots (including female hormones, aspirin, and
some non-aspirin pain relievers) should stop these
medications prior to surgery to lower the risk that
a hematoma will form. A hematoma, a pocket of
GALE ENCYCLOPEDIA OF MEDICINE

Face lift surgery can be performed on an outpatient basis with local anesthetics. Patients typically
also receive ‘‘twilight anesthesia,’’ an intravenous
sedative that helps to lower their awareness of the
procedure being performed.
There are a number of variations of face lift surgery. Which one is used will depend on the patient’s
facial structure, how much correction is needed, and the
preferences of the surgeon performing the procedure.
In a typical face lift surgery, the surgeon begins by
making an incision within the hairline just above the
ear. The incision continues down along the front edge
of the ear, around the earlobe, and then up and behind
the ear extending back into the hairline. The location of
this incision is designed to hide any sign of the procedure later. The same procedure is repeated on the other
side of the face. Using various instruments, the surgeon
will then work to separate the skin of the face from its
underlying tissue, moving down to the cheek and into
the neck area and below the chin. Fat deposits over the
cheeks and in the neck may be removed surgically or
with liposuction at this time. The surgeon will then
work to free up and tighten certain bands of muscle
and tissue that extend up from the shoulder, below the
chin, and up and behind the neck. If these muscles and
tissue are not tightened, the looseness and sagging
appearance of the skin will return. The surgeon then
trims excess skin from the edges of the original incision,
pulls the skin back, and staples or sutures it into place.

Preparation
Prior to the procedure, patients meet with their
surgeon to discuss the surgery, clarify the results that
1421

Face lift

can be achieved, and discuss the potential problems that
can occur. Having realistic expectations is important in
any cosmetic procedure. Patients will learn, for example,
that although face lift surgery can improve the contour
of the face and neck, other procedures will be necessary
to reduce the appearance of many wrinkles. As mentioned earlier, patients will stop taking aspirin, birth
control or female hormones, and other medications
affecting blood clotting about two weeks before the
procedure. Some physicians prescribe vitamin C and K
in the belief that this promotes healing. Patients will also
be advised to stop smoking and to avoid exposure to
passive smoke before the procedure and afterward.
Some surgeons also recommend antibiotics be taken
beforehand to limit the risk of infection. Some surgeons
also use a steroid injection before or after the procedure,
to reduce swelling.

Aftercare
After the surgery, a pressure bandage will be
applied to the face to reduce the risk of hematoma.
The patient may spend a few hours resting in a recovery room to ensure no bleeding has occurred. The
patient then returns home. Some surgeons recommend
that the patient remain reclining for the next 24 hours,
consuming a liquid diet, and avoiding any movements
that lead the neck to flex. Ice packs for the first few
days can help to reduce swelling and lower the risk of
hematoma. Patients continue taking an antibiotic
until the first stitches come out about five days after
the procedure. The balance are removed seven to ten
days later. Many patients return to work and limited
activities within two weeks of the procedure.

Risks
The major complication seen following face lift
surgery is a hematoma. If a hematoma forms, the
patient may have to return to have the stitches
reopened to find the source of the bleeding. Most
hematomas form within 48 hours of surgery. The
typical sign is pain or swelling affecting one side of
the face but not the other.
Another risk of face lift surgery is nerve damage.
Sometimes it can affect the patient’s ability to raise an
eyebrow, or distort his smile, or leave him with limited
feeling in his earlobe. Most of these nerve injuries,
however, repair themselves within 2–6 months.

In a typical face lift surgery, the surgeon begins by making an
incision within the hairline just above the ear. The incision
continues down along the front of the ear, around the earlobe,
and then up and behind the ear extending back into the
hairline, as shown above. The same procedure is repeated
on the other side of the face. The surgeon will then separate
the skin from the tissue, remove fat deposits over the
cheeks and neck, tighten up muscles and tissues below the
chin and upwards behind the neck. The surgeon then
trims excess skin from the original incision, pulls the skin
back, and sutures it into place. (Illustration by Electronic
Illustrators Group.)

KEY TERMS
Hematoma—A complication of surgery in which a
collection of blood forms below the skin.
Rhytidectomy—It literally means ‘‘wrinkle excision.’’ It is another, misleading, term for face lift
surgery.
Twilight anesthesia—An intravenous mixture of
sedatives and other medications that decreases
patients’ awareness of the procedure being
performed.

a noticeable improvement in the contour of his face and
neck. Some fine wrinkling of the skin may be improved,
but deep wrinkles are likely to require another cosmetic
procedure to improve their appearance.

Abnormal results
Normal results
Some swelling and bruising is normal following face
lift surgery. After these disappear, the patient should see
1422

In addition to the risks outlined above, other
complications of face lift surgery include infection,
scarring, and hair loss near incision lines.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Society for Dermatologic Surgery. 930 N.
Meacham Road, PO Box 4014, Schaumburg,
IL 60168-4014. (847) 330-9830. <http://
www.asds-net.org>.
American Society of Plastic and Reconstructive Surgeons.
44 E. Algonquin Rd., Arlington Heights,
IL 60005. (847) 228-9900. <http://
www.plasticsurgery.org>.

Richard H. Camer

other caregivers. The parent may falsify the child’s
medical history or tamper with laboratory tests in
order to make the child appear sick. Occasionally,
they may actually injure the child to assure that the
child will be treated.
Ganser’s syndrome
Ganser’s syndrome is an unusual dissociative
reaction to extreme stress in which the patient gives
absurd or silly answers to simple questions. It has
sometimes been labeled as psychiatric malingering,
but is more often classified as a factitious disorder.

Causes and symptoms

Factitious disorders
Definition
Factitious disorders are a group of mental disturbances in which patients intentionally act physically
or mentally ill without obvious benefits. The name
factitious comes from a Latin word that means
artificial. These disorders are not malingering, which
is defined as pretending illness when the ‘‘patient’’ has
a clear motive, such as financial gain.

Description
Patients with factitious disorders produce or exaggerate the symptoms of a physical or mental illness by
a variety of methods, including contaminating urine
samples with blood, taking hallucinogens, injecting
themselves with bacteria to produce infections, and
other similar behaviors.
There are no reliable statistics on the frequency
of factitious disorders, but they are more common in
men than in women. The following conditions are
sometimes classified as factitious disorders:
Munchausen syndrome
Munchausen syndrome refers to patients whose
factitious symptoms are dramatized and exaggerated.
Many persons with Munchausen go so far as to
undergo major surgery repeatedly, and, to avoid
detection, at several locations. Many have been
employed in hospitals or in health care professions.
The syndrome’s onset is in early adulthood.
Munchausen by proxy
Munchausen by proxy is the name given to factitious disorders in children produced by parents or
GALE ENCYCLOPEDIA OF MEDICINE

No single explanation of factitious disorders
covers all cases. These disorders are variously attributed to underlying personality disorders; child abuse;
the wish to repeat a satisfying childhood relationship
with a doctor; and the desire to deceive or test
authority figures. Also, the wish to assume the role
of patient and be cared for is involved. In many cases,
the suffering of a major personal loss has been
implicated.
The following are regarded as indications of a
factitious disorder:


dramatic but inconsistent medical history



extensive knowledge of medicine and/or hospitals



negative test results followed by further symptom
development



symptoms that occur only when the patient is not
being observed



few visitors



arguments with hospital staff or similar acting-out
behaviors



eagerness to
procedures

undergo

operations

and

other

When patients with factitious disorders are
confronted, they usually deny that their symptoms
are intentional. They may become angry and leave
the hospital. In many cases they enter another
hospital, which has led to the nickname ‘‘hospital
hoboes.’’

Diagnosis
Diagnosis of factitious disorders is usually
based on the exclusion of bona fide medical or
psychiatric conditions, together with a combination of the signs listed earlier. In some cases, the
1423

Factitious disorders

Resources

Failure to thrive

KEY TERMS
Ganser’s syndrome—An unusual factitious disorder characterized by dissociative symptoms and
absurd answers to direct questions.
Malingering—Pretending to be sick in order to be
relieved of an unwanted duty or obtain some other
obvious benefit.
Munchausen by proxy—A factitious disorder in
children produced by a parent or other caregiver.
Munchausen syndrome—A factitious disorder in
which the patient’s symptoms are dramatized and
exaggerated.

diagnosis is made on the basis of records from other
hospitals.

Treatment
Treatment of factitious disorders is usually limited
to prompt recognition of the condition and the refusal
to give unnecessary medications or to perform
unneeded procedures. Factitious disorder patients do
not usually remain in the hospital long enough for
effective psychiatric treatment. Some clinicians have
tried psychotherapeutic treatment for factitious
disorder patients, and there are anecdotal reports
that antidepressant or antipsychotic medications are
helpful in certain cases.

Prognosis
Some patients have only one or two episodes of
factitious disorders; others develop a chronic form
that may be lifelong. Successful treatment of the
chronic form appears to be rare.
Resources
BOOKS

Eisendrath, Stuart J. ‘‘Psychiatric Disorders.’’ In Current
Medical Diagnosis & Treatment, 1998, edited by
Stephen J. McPhee, et al., 37th ed. Stamford: Appleton
& Lange, 1997.

Rebecca J. Frey, PhD

Factor VIII deficiency see Hemophilia
Factor IX deficiency see Hemophilia
1424

Failure to thrive
Definition
Failure to thrive (FTT) is used to describe a delay
in a child’s growth or development. It is usually applied
to infants and children up to two years of age who do
not gain or maintain weight as they should. Failure to
thrive is not a specific disease, but rather a cluster of
symptoms which may come from a variety of sources.

Description
Shortly after birth most infants loose some
weight. After that expected loss, babies should gain
weight at a steady and predictable rate. When a baby
does not gain weigh as expected, or continues to loose
weight, it is not thriving. Failure to thrive may be due
to one or more conditions.
Organic failure to thrive (OFTT) implies that
the organs involved with digestion and absorption
of food are malformed or incomplete so the baby
cannot digest its food. Non-organic failure to thrive
(NOFTT) is the most common cause of FTT and
implies the baby is not receiving enough food due
to economic factors or parental neglect, or do to
psychosocial problems.

Causes and symptoms
Occasionally, there may be an underlying physical
condition that inhibits the baby’s ability to take in,
digest, or process food. These defects can occur in the
esophagus, stomach, small or large intestine, rectum or
anus. Usually the defect is an incomplete development
of the organ, and it must be surgically corrected. Most
physical defects can be detected shortly after birth.
Failure to thrive may also result from lack of
available food or the quality of the food offered.
This can be due to economic factors in the family,
parental beliefs and concepts of nutrition, or neglect
of the child. In addition, if the baby is being breast
fed, the quality or quantity of the mother’s milk may
be the source of the problem.
Psychosocial problems, often stemming from a
lack of nurturing parent-child relations can lead to a
failure to thrive. The child may exhibit poor appetite
due to depression from insufficient attention from
parents.
Infants and toddlers, whose growth is substantially less than expected, are considered to be suffering
from FTT.
GALE ENCYCLOPEDIA OF MEDICINE

Most babies are weighed at birth and that weight
is used as a base line for future well-baby check-ups.
If the baby is not gaining weight at a predictable rate,
the doctor will do a more extensive examination. If
there are no apparent physical deformities in the
digestive tract, the doctor will examine the child’s
environment. As part of that examination, the doctor
will look at the family history of height and weight. In
addition, the parents will be asked about feedings,
illnesses, and family routines. If the mother is breastfeeding the doctor will also evaluate her diet, general
health, and well being as it affects the quantity and
quality of her milk.
Diagnosis of FTT is confirmed by a positive
growth and behavioral response to increased nutrition.

Treatment
If there is an underlying physical reason for failure to thrive, such as a disorder of swallowing
mechanism or intestinal problems, correcting that
problem should reverse the condition. If the condition is caused by environmental factors, the physician
will suggest several ways parents may provide
adequate food for the child. Maternal education
and parental counseling may also be recommended.
In extreme cases, hospitalization or a more nurturing
home may be necessary.

Prognosis
The first year of life is important as a foundation
for growth and physical and intellectual development in the future. Children with extreme failure to
thrive in the first year may never catch up to their
peers even if their physical growth improves. In
about one third of these extreme cases, mental
development remains below normal and roughly
half will continue to have psychosocial and eating
problems throughout life.
When failure to thrive is identified and corrected
early, most children catch up to their peers and remain
healthy and well developed.

Prevention
Initial failure to thrive caused by physical defects
cannot be prevented but can often be corrected before
they become a danger to the child. Maternal education
and emotional and economic support systems all help
to prevent failure to thrive in those cases where there
is no physical deformity.
GALE ENCYCLOPEDIA OF MEDICINE

Fainting

Diagnosis

KEY TERMS
Esophagus—The muscular tube which connects
the mouth and stomach.
Psychosocial—A term referring to the mind’s ability to, consciously or unconsciously, adjust and
relate the body to its social environment.

Resources
ORGANIZATIONS

American Humane Association, Children’s Division. 63
Inverness Drive East, Englewood, CO 80112-5117.
(800) 227-4645. <www.americanhumane.org>.
Federation for Children With Special Needs. 1135 Tremont
Street, Suite 420, Boston, MA 02120. (617) 236-7210.
<http://www.fcsn.org>.
National Digestive Diseases Information Clearinghouse. 2
Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.

Dorothy Elinor Stonely

Fainting
Definition
Fainting is loss of consciousness caused by a
temporary lack of oxygen to the brain. Known by
the medical term ‘‘syncope,’’ fainting may be preceded by dizziness, nausea, or a feeling of extreme
weakness.

Description
When a person faints, the loss of consciousness is
brief. The person will wake up as soon as normal
blood flow is restored to the brain. Blood flow is
usually restored by lying flat for a short time. This
position puts the head on the same level as the heart so
that blood flows more easily to the brain.
A fainting episode may be completely harmless
and of no significance, but it can be a symptom of a
serious underlying disorder. No matter how trivial it
seems, a fainting episode should be treated as a
medical emergency until the cause is determined.
1425

Fainting

Causes and symptoms
Extreme pain, fear, or stress may bring on fainting. This type of fainting is caused by overstimulation
of the vagus nerve, a nerve connected to the brain that
helps control breathing and circulation. In addition, a
person who stands still or erect for too long may faint.
This type of fainting occurs because blood pools in the
leg veins, reducing the amount that is available for the
heart to pump to the brain. This type of fainting is
quite common in older people or those taking drugs to
treat high blood pressure.
When an older person feels faint upon turning the
head or looking upward suddenly, the cause could be
osteoarthritis of the neck bones. Osteoarthritis
damages the cartilage between the neck bones and
causes pressure on blood vessels leading to the brain.
Fainting can be a symptom of a disease such as
Stokes-Adams syndrome, a condition in which blood
flow to the brain is temporarily reduced because of an
irregular heartbeat. Some people may experience fainting associated with weakness in the limbs or a temporary problem in speaking caused by obstructed blood
flow in vessels passing through the neck to the brain.
Pregnant women frequently feel faint. Fainting may
also occur as a result of low blood sugar. Low blood
sugar can occur if a person skips a meal or has diabetes.
Fainting can also be caused by:


prolonged coughing



straining to defecate or urinate



blowing a wind instrument too hard



remaining in a stuffy environment with too little
oxygen

Sometimes fainting may be caused by a temporary
drop in the blood supply to the brain caused by a
transient ischemic attack (TIA). A TIA, sometimes
called a mini-stroke, is a disruption in the blood supply
to the brain caused by a blocked or burst blood vessel.
Seek help immediately if a fainting spell is followed by
one or more of the symptoms listed below:


numbness or tingling in any body part



blurred vision



confusion



difficulty speaking



loss of movement in arms or legs

A few seconds before fainting, a person may sweat
or become pale, feel nauseated or dizzy, and have
blurred vision or racing heartbeat. Once the person
loses consciousness, the pupils may dilate as the heart
1426

If a person is feeling faint, unconsciousness may be
prevented by sitting with the head between the knees, as
shown in the illustration above, or by lying flat with the legs
raised. (Illustration by Electronic Illustrators Group.)

rate slows down. There may be abnormal movements.
Muscles may tighten or the back may arch. These
movements do not last long and they are not violent.
In most cases, the patient regains consciousness
within a few minutes, but the fainting spell may be
followed by nervousness, headache, nausea, dizziness,
pallor or sweating. The person may faint again, especially if he or she stands up within 30 minutes.

Diagnosis
Most episodes of fainting are a one-time occurrence. When a person experiences repeated fainting
spells, a physician should be consulted.

Treatment
Most of the time, a person who faints ends up lying
on the floor. If this happens, the patient should be
rolled onto his or her back. Because someone who
faints often vomits, bystanders should keep the airway
open. A person who is fainting should not be held
upright or in a sitting position. These positions prevent
blood flow to the brain and may bring on a seizure.
Bystanders should check the patient’s breathing
and pulse rate. The pulse may be weak and slow. If
there are no signs of breathing or heart rate, the problem is more serious than fainting, and cardiopulmonary resuscitation (CPR) must begin.
If breathing and pulse rates seem normal, the
person’s legs should be raised above the level of the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Osteoarthritis—A disease characterized by damage
to the cartilage in the joints. The joints become
inflamed, deformed, and enlarged, and movement
becomes painful.
Stokes-Adams syndrome—Recurrent episodes of
temporary loss of consciousness (fainting) caused
by an insufficient flow of blood from the heart to the
brain. This syndrome is caused by a very rapid or a
very slow heartbeat.
Transient ischemic attack (TIA)—A brief interruption of the blood supply to part of the brain that
causes a temporary impairment of vision, speech,
or movement. Usually, the episode lasts for just a
few moments, but it may be a warning sign for a
full-scale stroke.
Vagus nerve—A cranial nerve, that is, a nerve connected to the brain. The vagus nerve has branches
to most of the major organs in the body, including
the larynx, throat, windpipe, lungs, heart, and most
of the digestive system.

head so that gravity can help the blood flow to the
brain. Belts, collars or any other constrictive clothing
should be loosened.
If the person does not regain consciousness within
a minute or two after fainting, medical help should be
summoned.

Prognosis
After a fainting spell, the person should regain
normal color but may continue to feel weak for a
short time. Lying down quietly for a few moments
may help.
In most cases, an attack of fainting is not serious.
As soon as the underlying pain or stress passes, the
danger of repeated episodes also is eliminated.

Prevention
If a person is feeling faint, unconsciousness may
be prevented by sitting with the head between the
knees or lying flat with the legs raised.
A person who has fainted should lie flat for 10–15
minutes after regaining consciousness to give the
system a chance to regain its balance. Standing up
too soon may bring on another fainting spell.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Greenberg, David A., et al. Clinical Neurology. 2nd ed.
Norwalk, CT: Appleton & Lange, 1993.

Carol A. Turkington

Falciparum malaria see Malaria
Fallopian tube ligation see Tubal ligation
Fallopian tube removal see Salpingectomy
Fallopian tube x rays see
Hysterosalpingography
Famciclovir see Antiviral drugs

Familial Mediterranean fever
Definition
Familial Mediterranean fever (FMF) is an inherited
disorder of the inflammatory response characterized by
recurring attacks of fever, accompanied by intense pain
in the abdomen, chest, or joints. Attacks usually last
12–72 hours, and can occasionally involve a skin rash.
Kidney disease is a serious concern if the disorder is not
treated. FMF is most prevalent in people of Armenian,
Sephardic-Jewish, Arabic, and Turkish ancestry.

Description
FMF could be described as a disorder of ‘‘inappropriate’’ inflammation. That is, an event that in a
normal situation causes a mild or unnoticeable
inflammation might cause a severe inflammatory
response in someone with FMF. Certain areas of
the body are at risk for FMF-related symptoms. A
serosa is a serous (fluid-producing) membrane that
can be found inside the abdominal cavity (peritoneum), around the lungs (pleura), around the heart
(pericardium), and inside the joints (synovium). The
symptoms of FMF are due to inflammation of one or
more of the serosal membranes (serositis). Thus,
FMF is also sometimes called recurrent polyserositis.
During an attack, large numbers of neutrophils, a
type of white blood cell, move into the affected areas
causing painful inflammation and fever. These episodes may be accompanied by a skin rash or joint
pain. In a few cases, chronic arthritis is a problem.
Amyloidosis is a potentially serious condition in which
proteins called amyloids are mistakenly produced and
1427

Familial Mediterranean fever

Resources

Familial Mediterranean fever

deposited in organs and tissues throughout the body.
Left untreated, amyloidosis often leads to kidney failure, which is the major long-term health risk in FMF.
In most cases, the attacks of fever and pain are
first noticed in childhood or adolescence. The interval
between these episodes may be days or months, and is
not predictable. However, during these intervals people with FMF typically lead normal lives. It is not
entirely clear what brings on an attack, but people
with FMF often report mild physical trauma, physical
exertion, or emotional stress just prior to the onset of
symptoms. Treatment for FMF involves an oral medication called colchicine, which is highly effective for
the episodes of fever and pain, as well as for amyloidosis and the kidney disease that can result from it.
FMF is most common in certain ethnic groups
from the eastern Mediterranean region, but cases in
other ethnic groups in other parts of the world are
increasingly being reported. FMF is also known by
many other names. They include: recurrent hereditary
polyserositis, benign paroxysmal peritonitis, familial
paroxysmal polyserositis, paroxysmal polyserositis,
familial recurrent polyserositis, periodic fever, periodic
amyloid syndrome, periodic peritonitis syndrome,
Reimann periodic disease, Reimann syndrome, SiegelCattan-Mamou syndrome, and Armenian syndrome.
Estimates of the incidence of FMF in specific
eastern Mediterranean populations range from 1 in
2000 to 1 in 100, depending on the population studied.
Specific mutations in the MEFV gene are more
common in certain ethnic groups, and may cause a
somewhat different course of the disease. A few mutations in the MEFV gene likely became common in a
small population in the eastern Mediterranean several
thousand years ago. It is postulated that carrying a
single copy of a mutated gene produced a modified
(but not abnormal) inflammatory response that may
have been protective against some infectious agent at
that time. Those who carried a single ‘‘beneficial’’
mutation in the MEFV gene were more likely to
survive and reproduce, which may explain the high
carrier frequency (up to one in five) in some populations. People of Armenian, Sephardic-Jewish, Arabic,
and Turkish ancestry are at greatest risk for FMF.
However, a better understanding and recognition of
the symptoms of FMF in recent years has resulted in
more reports of the condition in other ethnic groups,
such as Italians and Armenian-Americans.

(short for Mediterranean Fever) on chromosome
number 16 are the underlying cause of FMF.
Autosomal recessive inheritance implies that a person
with FMF has mutations in both copies of the MEFV
gene. All genes come in pairs, and one copy of each
pair is inherited from each parent. If neither parent
of a child with FMF has the condition, it means
they carry one mutated copy of the MEFV gene,
but also one normal copy, which is enough to protect
them from disease. If both parents carry the same
autosomal recessive gene, there is a one in four
chance in each pregnancy that the child will inherit
both recessive genes, and thus have the condition.
The MEFV gene carries the instructions for
production of a protein called pyrin, named for
pyrexia, a medical term for fever. The research group
in France that co-discovered the protein named it
marenostrin, after ancient Latin words that referred
to the Mediterranean Sea. The movement of neutrophils into an area of the body where trauma or
infection has occurred is the major cause of inflammation, which is a normal process. Research has shown
that pyrin has some function in controlling neutrophils. In a situation where minor trauma or stress
occurs, some initial inflammation may follow, but a
functional pyrin protein is responsible for shuttingdown the response of neutrophils once they are no
longer needed. An abnormal pyrin protein associated
with FMF may be partly functional, but unstable. In
some instances, the abnormal pyrin itself seems to be
‘‘stressed’’, and loses its ability to regulate neutrophils
and inflammation. Left unregulated, a normal, mild
inflammation spirals out of control. Exactly what
causes pyrin in FMF to lose its ability to control
neutrophils in some situations is not known.
The recurrent acute attacks of FMF typically
begin in childhood or adolescence. Episodes of fever
and painful inflammation usually last 12–72 hours.
About 90% of people with FMF have their first attack
by age 20. The group of symptoms that characterizes
FMF includes the following:
Fever
An FMF attack is nearly always accompanied by
a fever, but it may not be noticed in every case. Fevers
are typically 100–104 8F (38–40 8C). Some people
experience chills prior to the onset of fever.
Abdominal pain

Causes and symptoms
FMF is a genetic condition inherited in an autosomal recessive fashion. Mutations in the MEFV gene
1428

Nearly all people with FMF experience abdominal pain at one point or another, and for most it is the
most common complaint. The pain can range from
GALE ENCYCLOPEDIA OF MEDICINE

Chest pain
Pleuritis, also called pleurisy, occurs in up to half
of the affected individuals in certain ethnic groups.
The pain is usually on one side of the chest.
Pericarditis would also be felt as chest pain.
Joint pain
About 50% of people with FMF experience joint
pain during attacks. The pain is usually confined to
one joint at a time, and often involves the hip, knee, or
ankle. For some people, however, the recurrent joint
pain becomes chronic arthritis.
Myalgia
Up to 20% of individuals report muscle pain.
These episodes typically last less than two days, and
tend to occur in the evening or after physical exertion.
Rare cases of muscle pain and fever lasting up to one
month have been reported.
Skin rash
A rash, described as erysipelas-like erythema,
accompanies attacks in a minority of people, and
most often occurs on the front of the lower leg or top
of the foot. The rash appears as a red, warm, swollen
area about 4–6 in (10–15 cm) in diameter.
Amyloidosis
FMF is associated with high levels in the blood of
a protein called serum amyloid A (SAA). Over time,
excess SAA tends to be deposited in tissues and organs
throughout the body. The presence and deposition of
excess SAA is known as amyloidosis. Amyloidosis
may affect the gastrointestinal tract, liver, spleen,
heart, and testes, but effects on the kidneys are of
greatest concern. The frequency of amyloidosis varies
among the different ethnic groups, and its overall
incidence is difficult to determine because of the use
of colchicine to avert the problem. Left untreated,
however, those individuals who do develop amyloidosis of the kidneys may require a renal transplant, or
may even die of renal failure. The frequency and
severity of a person’s attacks of fever and serositis
seem to have no relation to whether they will develop
amyloidosis. In fact, a few people with FMF have been
GALE ENCYCLOPEDIA OF MEDICINE

described who have had amyloidosis but apparently
no other FMF-related symptoms.
Other symptoms
A small percentage of boys with FMF develop
painful inflammation around the testes, headaches
are a common occurrence during attacks, and certain
types of vasculitis (inflammation of the blood vessels)
seem to be more common in FMF.

Diagnosis
Individually, the symptoms that define FMF are
common. Fevers occur for many reasons, and nonspecific pains in the abdomen, chest, and joints are also
frequent ailments. Several infections can result in
symptoms similar to FMF (Mallaret meningitis, for
instance), and many people with FMF undergo
exploratory abdominal surgery and ineffective treatments before they are finally diagnosed. Membership
in a less commonly affected ethnic group may delay or
hinder the correct diagnosis.
In general, symptoms involving one or more of
the following broad groups should lead to suspicion
of FMF: Unexplained recurrent fevers, polyserositis,
skin rash, and/or joint pain; abnormal blood studies
(see below); and renal or other disease associated
with amyloidosis. A family history of FMF or its
symptoms would obviously be an important clue,
but the recessive nature of FMF means there usually
is no family history. The diagnosis may be confirmed
when a person with unexplained fever and pain
responds to treatment with colchicine since colchicine is not known to have a beneficial effect on any
other condition similar to FMF. Abnormal results on
a blood test typically include leukocytosis (elevated
number of neutrophils in the blood), an increased
erythrocyte sedimentation rate (rate at which red
blood cells form a sediment in a blood sample), and
increased levels of proteins associated with inflammation (called acute phase reactants) such as SAA.
Direct analysis of the MEFV gene for FMF
mutations is the only method to be certain of the
diagnosis. However, it is not yet possible to detect all
MEFV gene mutations that might cause FMF. Thus,
if DNA analysis is negative, clinical methods must be
relied upon. If both members of a couple were proven
to be FMF carriers through genetic testing, highly
accurate prenatal diagnosis would be available in any
subsequent pregnancy.
Similar syndromes of periodic fever and inflammation include familial Hibernian fever and
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Familial Mediterranean fever

mild to severe, and can be diffuse or localized. It can
mimic appendicitis, and many people with undiagnosed FMF have had appendectomies or exploratory
surgery of the abdomen done, only to have the fever
and abdominal pain return.

Familial Mediterranean fever

hyperimmunoglobulinemia D syndrome, but both are
more rare than FMF.

Treatment
Colchicine is a chemical compound that can be
used as a medication, and is frequently prescribed for
gout. Some years ago, colchicine was discovered to
also be effective in reducing the frequency and severity
of attacks in FMF. Treatment for FMF at this point
consists of taking colchicine daily. Studies have shown
that about 75% of FMF patients achieve complete
remission of their symptoms, and about 95% show
marked improvement when taking colchicine. Lower
effectiveness has been reported, but there is some
question about the number of FMF patients who
choose not to take their colchicine between attacks
when they are feeling well, and thus lose some of the
ability to prevent attacks. Compliance with taking
colchicine every day may be hampered by its side
effects, which include diarrhea, nausea, abdominal
bloating, and gas. There is a theoretical risk that colchicine use could damage chromosomes in sperms and
eggs, or in an embryo during pregnancy, or that it
might reduce fertility. However, studies looking at
reproduction in men and women who have used
colchicine have so far not shown any increased risks.
Colchicine is also effective in preventing, delaying, or
reversing renal disease associated with amyloidosis.
Other medications may be used as needed to deal
with the pain and fever associated with FMF attacks.
Dialysis and/or renal transplant might become necessary in someone with advanced kidney disease. Given
its genetic nature, there is no cure for FMF, nor is
there likely to be in the near future. Any couple that
has a child diagnosed with FMF, or anyone with a
family history of the condition (especially those in
high-risk ethnic groups), should be offered genetic
counseling to obtain the most up-to-date information
on FMF and testing options.

KEY TERMS
Acute phase reactants—Blood proteins whose
concentrations increase or decrease in reaction to
the inflammation process.
Amyloid—A waxy translucent substance composed mostly of protein, that forms plaques (abnormal deposits) in the brain.
Amyloidosis—Accumulation of amyloid deposits
in various organs and tissues in the body such that
normal functioning of an organ is compromised.
Colchicine—A compound that blocks the assembly
of microtubules–protein fibers necessary for cell
division and some kinds of cell movements, including neutrophil migration. Side effects may include
diarrhea, abdominal bloating, and gas.
Leukocyte—A white blood cell. The neutrophils
are a type of leukocyte.
Leukocytosis—An increase in the number of leukocytes in the blood.
Neutrophil—The primary type of white blood cell
involved in inflammation. Neutrophils are a type of
granulocyte, also known as a polymorphonuclear
leukocyte.
Pericarditis—Inflammation of the pericardium, the
membrane surrounding the heart.
Peritonitis—Inflammation of the peritoneum, the
membrane surrounding the abdominal contents.
Pleuritis—Inflammation of the pleura, the membrane surrounding the lungs.
Pyrexia—A medical term denoting fevers.
Serositis—Inflammation of a serosal membrane.
Polyserositis refers to the inflammation of two or
more serosal membranes.
Synovitis—Inflammation of the synovium, a membrane found inside joints.

Prognosis
For those individuals who are diagnosed early
enough and take colchicine consistently, the prognosis
is excellent. Most will have very few, if any, attacks of
fever and polyserositis, and will likely not develop
serious complications of amyloidosis. The problem
of misdiagnosing FMF continues, but education
attempts directed at both the public and medical care
providers should improve the situation. Future
research should provide a better understanding of
the inflammation process, focusing on how neutrophils are genetically regulated. That information
1430

could then be used to develop treatments for FMF
with fewer side effects, and might also assist in developing therapies for other diseases in which abnormal
inflammation and immune response are a problem.
Resources
ORGANIZATIONS

National Institute of Arthritis and Musculoskeletal and
Skin Diseases. National Institutes of Health, One
AMS Circle, Bethesda, MD 20892. <http://
www.nih.gov/niams>.
GALE ENCYCLOPEDIA OF MEDICINE

Scott J. Polzin, M.S.

FAP is a rare disease. One in 8,000 people in the
United States have FAP. However, it may be very
common in affected families. FAP is inherited in an
autosomal dominant pattern. This means that a
person with FAP has a 50% chance of passing the
condition down to each of their children. FAP can
also develop in someone with no family history of
the disorder, due to a new genetic mutation in that
individual. It is thought that approximately one
percent of all colorectal cancers in the United States
can be attributed to FAP.

Causes and symptoms

Familial polyposis
Definition
Familial polyposis is an inherited condition which
primarily affects the large intestine (colon and rectum). Large numbers of projecting masses of swollen
and thickened or tumorous membrane (polyps)
develop on the inner lining of this part of the bowel.
The polyps eventually become malignant.

Description
Familial polyposis (FP) is known by many
synonyms, most include some combination of words
which reflect what is known about the disease. As the
disease is inherited, the word, family, is often included.
Because these mushroom-like growths are the most
obvious manifestation of the disorder, the word,
polyp, is usually in the term as well. Adenoma
refers to the particular kind of polyp that is typically
discovered. Some of the names found in medical texts
and journals include polyposis coli, familial colonic
polyposis, multiple familial polyposis, familial adenomatous colon polyposis, adenomatosis of the colon
and rectum (ACR), and familial adenomatous
polyposis (FAP). The last term and its abbreviation
have been commonly used since the early 1990s. It will
be used in this discussion.
Familial polyposis or familial adenomatous
polyposis (FAP) is a premalignant disease. This
means that a person with FAP, if left untreated, will
invariably develop cancer. Individuals with this
disorder grow hundreds of polyps throughout their
large intestines. The polyps, which may also be called
adenomas, commonly develop just after puberty.
Approximately half of all FAP patients will have
polyps by age 14. Ninety percent will have detectable
polyps by age 25. Usually by age 35–40, one or more of
these polyps will become cancerous.
GALE ENCYCLOPEDIA OF MEDICINE

FAP is caused by a portion of a gene that mutates
or changes. The original cause of the mutation is
unknown. Its exact role in FAP is not completely
clear. Researchers theorize that the normal gene
directs the manufacture of a protein which helps control cell growth. The mutated gene section in FAP
generates an abnormal protein which does not
perform its normal function. Cells grow out of control,
causing the development of multiple, sometimes
hundreds, of polyps. One or more of these eventually
becomes cancerous.
Many individuals develop polyps without displaying any symptoms. Others experience such gastrointestinal problems as diarrhea, constipation,
abdominal cramps, blood in the stool, or weight loss.
FAP patients may also develop nonmalignant tumors
(desmoid tumors), and/or some bone and dental
abnormalities. In addition, they may exhibit a ‘‘spot’’
on the retina of the eye (congenital hypertrophy of the
retinal pigment epithelium, or CHRPE).
Relatives of individuals with diagnosed FAP are
at high risk of having the disease themselves. There are
no other known risk factors for this condition.

Diagnosis
The abnormal portion of the gene that causes
FAP in most patients can be detected. A blood test
can then be performed which identifies family members who have the same mutation. They will eventually
develop the condition. Children who have a parent
with FAP, and siblings of affected patients whose
parental history is incomplete, should be evaluated.
The polyps characteristic of FAP have been found in
children as young as age five. Testing of appropriate
individuals should take place as soon as the diagnosis
of FAP is established in one member of a family.
Relatives of people with diagnosed FAP should
exercise caution regarding where they seek advice and
1431

Familial polyposis

National Organization for Rare Disorders (NORD). PO
Box 8923, New Fairfield, CT 06812-8923. (203)
746-6518 or (800) 999-6673. Fax: (203) 746-6481.
<http://www.rarediseases.org>.
National Society of Genetic Counselors. 233 Canterbury
Dr., Wallingford, PA 19086-6617. (610) 872-1192.
<http://www.nsgc.org/GeneticCounselingYou.asp>.

Familial polyposis

testing. One study of a commercially available blood
test found that less than 20% of patients received any
genetic counseling, and almost one third of their physicians misinterpreted the test results.

screening eye examination to detect CHRPE, associated
with FAP, may also be performed.

Registries for FAP patients can be found at many
sites in the United States. Such a registry specializes in
identification, assistance, and education of people
with a particular disease, and is usually a separate
department in a research hospital. A team of health
professionals who have expertise in the disorder staff
the registry.

The only definitive treatment for FAP is surgical
removal of the lower intestine. Since the goal is to
prevent cancer, the operation is done as soon as
adenomatous polyps are found on sigmoidoscopy.
Waiting until a polyp becomes malignant is unsafe,
as the cancer may invade surrounding tissues.

Testing within a research setting and/or at a facility with a registry of patients with FAP is more likely
to safeguard against problems, such as the misunderstanding of test results. As part of a research project,
sometimes counseling as well as blood tests are available at no charge to the patient. Insurance coverage
varies. Concerns about confidentiality, and future
insurance and employment discrimination, may
prompt individuals to pay for the examination out of
pocket. Commercial blood tests cost approximately
$250 per sample.
If the abnormal gene is found in a family member,
annual screening for colon polyps is recommended,
beginning at age 11. Flexible sigmoidoscopy is used
for this examination. It is usually done in a physician’s
office, or in a hospital department, most often by a
gastroenterologist or a surgeon. Food intake may be
restricted for 24 hours prior to the procedure. Before
the study, the intestine is cleared of stool by one or
more small enemas. Some physicians prefer to sedate
the patient, to help them relax. Then a flexible, lighted,
hollow tube (sigmoidoscope) is inserted into the anus
and maneuvered into the large intestine. The physician
examines the wall of the colon to look for polyps. If
polyps are found, one or more may be removed for
biopsy.
Most patients report little discomfort during the
examination. The procedure itself takes five to fifteen
minutes. The patient may be at the facility an hour, or
more, if recovery from sedation is needed. If no medication was administered, driving and resumption of
normal activities are permitted immediately. The cost
of the procedure varies widely, but, as of 1997, it was
covered by Medicare, indicating the likelihood of
other types of insurance coverage.
In some cases the portion of the gene responsible
for FAP cannot be identified. Family members of these
patients cannot have a predictive blood test. The current recommendation is for these patients to have the
same annual examination with flexible sigmoidoscopy
as patients with a diagnosed FAP gene. A noninvasive
1432

Treatment

There are several choices about the type of surgery
to treat this condition. Some authorities advocate
removal of the colon, leaving the rectum or lowest
portion of the intestine in place. The small intestine
can be attached to the rectum, allowing normal bowel
function. This is often called ileorectal anastomosis.
Others argue that this section is also liable to develop
polyps, needs to be monitored regularly, and may
require eventual removal.
Excision of the entire lower intestine with preservation of normal bowel function is possible. This entails a
more complex surgical procedure. The patient may
experience more complications and a longer recovery
period. However, the risk of polyp development in this
area is very low. Periodic examination of the intestine
may not be needed once healing is complete.
The more intricate surgery may be referred to as a
J-pouch procedure, an ileal pouch-anal anastomosis, a
restorative proctocolectomy, or an ileoanal reservoir
procedure. It involves creating a ‘‘pouch’’ of tissue
from the small intestine, which is attached to the
anus. This serves as a reservoir or holding area for
stool, much as the rectum does normally. The surgery
is often done in several stages. A temporary ileostomy,
which creates an opening of the small intestines onto
the abdomen, is required. When all procedures are
completed, and after a recuperation period, the patient
regains normal bowel function through the anus.
Some researchers suggest that as genetic testing
becomes more developed, the specific portion of the
gene involved may dictate the type of surgery chosen.
Those at high risk of developing rectal polyps may be
advised to have the more complex operation. FAP
patients felt to be at lower risk for rectal polyps
might be counseled to consider the less radical surgery.
Medical therapy to treat the adenomatous
polyps has been attempted. Some nonsteroidal antiinflammatory drugs have been effective in reducing
the number and size of the polyps. It is possible that
these agents will be used as an additional treatment for
FAP, but they are unlikely to replace surgery.
GALE ENCYCLOPEDIA OF MEDICINE

National Organization for Rare Disorders. PO Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Gene—The basic unit of heredity, made of DNA.
Each gene occupies certain location on a
chromosome.
Mutation—An alteration in a gene, especially one
capable of producing a new trait, or a change in
function.

Ellen S. Weber, MSN

Family therapy
Individuals with FAP are at increased risk for cancers of the upper digestive tract including the upper
portion of the small bowel (dudodenum) and the channels where bile flows (biliary tract). Cancers of the
thyroid, pancreas, and adrenal gland are also more
commonly found among FAP patients. Periodic examination for the development of malignancy in these
areas is considered part of the treatment of FAP. In
some cases, such as cancer involving the duodenum, the
tests themselves carry a chance of complications. The
risk of the study must be weighed against the potential
benefits of knowing the results. Nonmalignant
growths, called desmoid tumors, also occur more frequently in patients with FAP. Although they are not
malignant, they grow quickly into surrounding tissues,
causing many difficulties, even death in some cases.

Prognosis
The major cause of death in many patients with
FAP remains colorectal cancer. One study suggested
that even with improved disease recognition, social
and emotional factors, such as fear of surgery, may
significantly delay a patient’s treatment. In recent
years, the trend is towards mortality from other
causes, such as desmoid tumors or cancers other than
colorectal. It has been estimated that a patient with
known FAP has a relative risk of dying over three
times greater than that of the average population, at
a given age.

Prevention
FAP cannot be prevented. Aggressive diagnosis,
treatment, and follow-up monitoring are keys to successful management of the disease.
Resources
ORGANIZATIONS

Familial Polyposis Registry. Department of Colorectal
Surgery. Cleveland Clinic Foundation. 9500 Euclid
Ave., Cleveland OH 44195-5001. (216) 444-6470.
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Family therapy is a form of psychotherapy that
involves all the members of a nuclear or extended
family. It may be conducted by a pair or team of
therapists. In many cases the team consists of a man
and a woman in order to treat gender-related issues or
serve as role models for family members. Although
some forms of family therapy are based on behavioral
or psychodynamic principles, the most widespread
form is based on family systems theory. This approach
regards the family, as a whole, as the unit of treatment,
and emphasizes such factors as relationships and
communication patterns rather than traits or symptoms in individual members.
Family therapy is a relatively recent development in
psychotherapy. It began shortly after World War II,
when doctors, who were treating schizophrenic patients,
noticed that the patients’ families communicated in disturbed ways. The doctors also found that the patients’
symptoms rose or fell according to the level of tension
between their parents. These observations led to considering a family as an organism or system with its own
internal rules, patterns of functioning, and tendency to
resist change. The therapists started to treat the families
of schizophrenic patients as whole units rather than
focusing on the hospitalized member. They found that
in many cases the family member with schizophrenia
improved when the ‘‘patient’’ was the family system.
(This should not be misunderstood to mean that schizophrenia is caused by family problems, although family
problems may worsen the condition.) This approach of
involving the entire family in the treatment plan and
therapy was then applied to families with problems
other than the presence of schizophrenia.
Family therapy is becoming an increasingly
common form of treatment as changes in American
society are reflected in family structures. It has led to
two further developments: couples therapy, which treats
relationship problems between marriage partners or gay
couples; and the extension of family therapy to religious
communities or other groups that resemble families.
1433

Family therapy

KEY TERMS

Family therapy

Purpose
Family therapy is often recommended in the
following situations:


Treatment of a family member with schizophrenia
or multiple personality disorder (MPD). Family
therapy helps other family members understand
their relative’s disorder and adjust to the psychological changes that may be occurring in the relative.



Families with problems across generational boundaries. These would include problems caused by
parents sharing housing with grandparents, or
children being reared by grandparents.



Families that deviate from social norms (commonlaw relationships, gay couples rearing children, etc.).
These families may not have internal problems but
may be troubled by outsiders’ judgmental attitudes.



Families with members from a mixture of racial,
cultural, or religious backgrounds.



Families who are scapegoating a member or undermining the treatment of a member in individual
therapy.



Families where the identified patient’s problems
seem inextricably tied to problems with other family
members.



Blended families with adjustment difficulties.

Most family therapists presuppose an average
level of intelligence and education on the part of
adult members of the family.

Precautions
Some families are not considered suitable candidates for family therapy. They include:


families in which one, or both, of the parents is
psychotic or has been diagnosed with antisocial or
paranoid personality disorder,



families whose cultural or religious values are
opposed to, or suspicious of, psychotherapy,



families with members who cannot participate
in treatment sessions because of physical illness or
similar limitations,



families with members with very rigid personality
structures. (Here, members might be at risk for an
emotional or psychological crisis),



families whose members cannot or will not be able to
meet regularly for treatment,



families that are unstable or on the verge of breakup.

1434

Description
Family therapy tends to be short-term treatment,
usually several months in length, with a focus on
resolving specific problems such as eating disorders,
difficulties with school, or adjustments to bereavement
or geographical relocation. It is not normally used for
long-term or intensive restructuring of severely dysfunctional families.
In family therapy sessions, all members of the
family and both therapists (if there is more than one)
are present at most sessions. The therapists seek to
analyze the process of family interaction and communication as a whole; they do not take sides with specific
members. They may make occasional comments or
remarks intended to help family members become
more conscious of patterns or structures that had
been previously taken for granted. Family therapists,
who work as a team, also model new behaviors for
the family through their interactions with each other
during sessions.
Family therapy is based on family systems theory,
which understands the family to be a living organism
that is more than the sum of its individual members.
Family therapy uses ‘‘systems’’ theory to evaluate
family members in terms of their position or role
within the system as a whole. Problems are treated
by changing the way the system works rather than
trying to ‘‘fix’’ a specific member. Family systems
theory is based on several major concepts:
The identified patient
The identified patient (IP) is the family member
with the symptom that has brought the family into
treatment. The concept of the IP is used by family
therapists to keep the family from scapegoating the
IP or using him or her as a way of avoiding problems
in the rest of the system.
Homeostasis (balance)
The concept of homeostasis means that the family
system seeks to maintain its customary organization
and functioning over time. It tends to resist change.
The family therapist can use the concept of homeostasis to explain why a certain family symptom has
surfaced at a given time, why a specific member has
become the IP, and what is likely to happen when
the family begins to change.
The extended family field
The extended family field refers to the nuclear
family, plus the network of grandparents and other
GALE ENCYCLOPEDIA OF MEDICINE

Differentiation
Differentiation refers to the ability of each family
member to maintain his or her own sense of self,
while remaining emotionally connected to the family.
One mark of a healthy family is its capacity to allow
members to differentiate, while family members still
feel that they are ‘‘members in good standing’’ of the
family.
Triangular relationships
Family systems theory maintains that emotional
relationships in families are usually triangular.
Whenever any two persons in the family system have
problems with each other, they will ‘‘triangle in’’ a
third member as a way of stabilizing their own
relationship. The triangles in a family system usually
interlock in a way that maintains family homeostasis.
Common family triangles include a child and its
parents; two children and one parent; a parent, a
child, and a grandparent; three siblings; or, husband,
wife, and an in-law.

Preparation
In some instances the family may have been
referred to a specialist in family therapy by their
pediatrician or other primary care provider. It is
estimated that as many as 50% of office visits to
pediatricians have to do with developmental problems in children that are affecting their families.
Some family doctors use symptom checklists or
psychological screeners to assess a family’s need for
therapy.
Family therapists may be either psychiatrists,
clinical psychologists, or other professionals certified
by a specialty board in marriage and family therapy.
They will usually evaluate a family for treatment by
scheduling a series of interviews with the members
of the immediate family, including young children,
and significant or symptomatic members of the
extended family. This process allows the therapist(s)
to find out how each member of the family sees the
problem, as well as to form first impressions of the
family’s functioning. Family therapists typically look
for the level and types of emotions expressed,
patterns of dominance and submission, the roles
played by family members, communication styles,
and the locations of emotional triangles. They will
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Blended family—A family formed by the remarriage of a divorced or widowed parent. It includes
the new husband and wife, plus some or all of their
children from previous marriages.
Differentiation—The ability to retain one’s identity
within a family system while maintaining emotional connections with the other members.
Extended family field—A person’s family of origin
plus grandparents, in-laws, and other relatives.
Family systems theory—An approach to treatment
that emphasizes the interdependency of family
members rather than focusing on individuals in isolation from the family. This theory underlies the most
influential forms of contemporary family therapy.
Genogram—A family tree diagram that represents
the names, birth order, sex, and relationships of the
members of a family. Therapists use genograms to
detect recurrent patterns in the family history and to
help the members understand their problem(s).
Homeostasis—The tendency of a family system
to maintain internal stability and resist change.
Identified patient (IP)—The family member in
whom the family’s symptom has emerged or is
most obvious.
Nuclear family—The basic family unit, consisting
of father, mother, and their biological children.
Triangling—A process in which two family members lower the tension level between them by
drawing in a third member.

also note whether these patterns are rigid or relatively
flexible.
Preparation also usually includes drawing a
genogram, which is a diagram that depicts significant
persons and events in the family’s history. Genograms
also include annotations about the medical history and
major personality traits of each member. Genograms
help in uncovering intergenerational patterns of behavior, marriage choices, family alliances and conflicts,
the existence of family secrets, and other information
that sheds light on the family’s present situation.

Risks
The chief risk in family therapy is the possible
unsettling of rigid personality defenses in individuals,
or couple relationships that had been fragile before the
1435

Family therapy

members of the extended family. This concept is used
to explain the intergenerational transmission of attitudes, problems, behaviors, and other issues.

Fanconi’s syndrome

beginning of therapy. Intensive family therapy may
also be difficult for psychotic family members.

Normal results
Normal results vary, but in good circumstances,
they include greater insight, increased differentiation
of individual family members, improved communication within the family, loosening of previously automatic behavior patterns, and resolution of the
problem that led the family to seek treatment.
Resources
BOOKS

Clark, R. Barkley. ‘‘Psychosocial Aspects of Pediatrics &
Psychiatric Disorders: Psychosocial Assessment of
Children & Families.’’ In Current Pediatric Diagnosis &
Treatment, edited by William W. Hay Jr., et al.
Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Famine fever see Relapsing fever

Fanconi’s syndrome
Definition
Fanconi’s syndrome is a set of kidney malfunctions
brought about by a variety of seemingly unrelated
disorders. Kidney malfunction leads to excessive urine
production and excessive thirst, resulting in deficits
of water, calcium, potassium, magnesium, and other
substances in the body. It often leads to bone disease
and stunted growth.

Description
Normally, kidneys cleanse the blood and keep its
salt, water, and acidity in balance, leaving what the
body needs in the blood and putting what the body
doesn’t need into the urine, which leaves the body.
This task is performed in two steps. First, the blood
is filtered through a kidney structure with small holes
that keep the cells and large molecules in the blood.
Second, some of the small molecules in the filtrate,
needed by the body, are reabsorbed and returned to
the bloodstream.
This reabsorption step is defective in Fanconi’s
syndrome. As a consequence, substances that are
normally reabsorbed, like glucose, amino acids, small
proteins, water, calcium, potassium, magnesium,
1436

bicarbonate, and phosphate, are lost and the body
becomes overly acidic.
Fanconi’s syndrome is also known as Fanconi
syndrome, renal Fanconi syndrome, Fanconi renaltubular syndrome, and Lignac-de Toni-Debré-Fanconi
syndrome. Fanconi’s anemia is, however, a totally
different disease.

Causes and symptoms
Causes
Fanconi’s syndrome can be caused by a variety
of genetic defects and by certain environmental
assaults.
The genetic diseases known to give rise to
Fanconi’s syndrome are cystinosis (the most common
cause in children), galactosemia, glycogen storage disease, hereditary fructose intolerance, Lowe syndrome,
Wilson disease, tyrosinemia, medullary cystic disease,
vitamin D dependency, and familial idiopathic
Fanconi’s syndrome.
Environmental assaults that cause Fanconi’s
syndrome include exposure to heavy metals (like
cadmium, lead, mercury, platinum, uranium), certain
drugs (like outdated tetracycline and gentamicin),
other substances (like Lysol, paraquat, toluene, the
amino acid lysine taken as a nutritional supplement),
and kidney transplantation.
Symptoms
Fanconi’s syndrome symptoms related directly
to impaired absorption include excessive urine
production and urination; excessive thirst; dehydration; constipation; anorexia nervosa; vomiting;
elevated levels of glucose, phosphate, calcium, uric
acid, amino acids, and protein (especially beta2microglobulin and lysozyme) in the urine; elevated
levels of chloride and decreased levels of phosphate
and calcium in the blood; and excessively acidic
blood.
The most noticeable indirect consequences of
impaired reabsorption are the bone diseases, rickets
and osteomalacia. Rickets affects children and is
associated with bone deformities, failure to grow,
and difficulty walking. If a person acquires
Fanconi’s syndrome as an adult, the bone disease is
termed osteomalacia and is accompanied by severe
bone pain and spontaneous fractures. Unlike rickets
due to malnutrition, these diseases cannot be reversed
with vitamin D. Muscle weakness and occasional
paralysis are other indirect consequences of the ineffective reabsorption.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis of Fanconi’s syndrome can be made by
urine and blood tests. It is also important to find the
underlying cause to decide on the best treatment. Other
symptoms specific to a particular patient will point to
other useful diagnostic tests. For example, high levels of
blood galactose in conjunction with symptoms of
Fanconi’s syndrome indicate the patient is suffering
from galactosemia, while high blood levels of cadmium
indicate the patient is suffering from cadmium poisoning.

Treatment
Fanconi’s syndrome is best treated by attacking
the underlying cause whenever possible. For example,
when cystinosis is treated with the drug cysteamine
to lower cystine levels in the body or Wilson disease
is treated with penicillamine to lower the levels of
copper, accompanying symptoms of Fanconi’s
syndrome will subside. If the patient has acquired the
disease from a heavy metal or another toxic agent, all
contact with the toxic agent should stop; the condition
will then likely disappear.
Nevertheless, additional treatment will be necessary either when it’s not possible to treat the underlying cause or while waiting for the kidneys to resume
normal function. This is done by restricting sodium
chloride (table salt), giving antacids to counteract
the excessive acidity of the blood, and supplying
potassium supplements.

KEY TERMS
Acidosis—Condition where the body is more
acidic than normal; associated with headache,
nausea, vomiting, and visual disturbances.
Fanconi’s anemia—An inherited form of aplastic
anemia.
Filtrate—The part of filtered material that flows
through the filter.
Idiopathic—Refers to a disease of unknown cause.
Polydipsia—Excessive thirst.
Polyuria—Excessive production of urine.

Fanconi’s syndrome caused by heavy metals and
other toxins can be prevented by avoiding these
substances.
Resources
ORGANIZATIONS

The American Society of Nephrology. 2025 M Street NW
#800, Washington, DC 20036. (202) 367-1190. <http://
www.asn-online.com>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.
OTHER

‘‘Online Mendelian Inheritance in Man.’’ OMIM
Homepage, <http://www.ncbi.nlm.nih.gov/Omim>.

Kidney transplant is the treatment of last resort,
used for patients whose kidneys have failed.

Prognosis
Fanconi’s syndrome can be reversible. Fanconi’s
syndrome caused by kidney transplantation usually
reverses itself within the first year after transplant
surgery. When caused by a toxin in the environment,
Fanconi’s syndrome generally can be reversed by
removing the causative agent from the patient’s environment. If it is caused by a genetic disease, it can
usually be reversed by treating the disease. However,
if Fanconi’s syndrome is not treated or if treatment is
unsuccessful, the kidneys can fail.

Prevention
Fanconi’s syndrome caused secondarily by the
genetic diseases galactosemia, glycogen storage disease, hereditary fructose intolerance, and tyrosinemia
is prevented by appropriate dietary restrictions to
treat the genetic disease, starting in infancy.
GALE ENCYCLOPEDIA OF MEDICINE

Lorraine Lica, PhD

Farsightedness see Hyperopia
FAS see Fetal alcohol syndrome

Fasciotomy
Definition
Fasciotomy is a surgical procedure that cuts away
the fascia to relieve tension or pressure.

Purpose
The fascia is thin connective tissue covering, or
separating, the muscles and internal organs of the
body. It varies in thickness, density, elasticity, and
composition, and is different from ligaments and
tendons.
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Fasciotomy

Diagnosis

Fasciotomy

The fascia can be injured either through constant
strain or through trauma. Fasciitis is an inflammation of the fascia. The most common condition for
which fasciotomy is performed is plantar fasciitis,
an inflammation of the fascia on the bottom of the
foot that is sometimes called a heel spur or stone
bruise.
Plantar fasciitis is caused by long periods on the
feet, being overweight, and wearing shoes that do not
support the foot well. Teachers, mail carriers, runners,
and others who make heavy use of their feet are
especially likely to suffer from plantar fasciitis.
Plantar fasciitis results in moderate to disabling
heel pain. If nine to twelve months of conservative
treatment (reducing time on feet, non-steroid
anti-inflammatory drugs, arch supports) under the
supervision of a doctor does not result in pain relief,
a fasciotomy may be done. Fasciotomy removes a
small portion of the fascia to relieve tension and
pain. Connective tissue grows back into the cut
space left by the cut, effectively lengthening the
fascia.
When a fasciotomy is performed on other parts of
the body, it is usually done to relieve pressure from a
compression injury to a limb. This type of injury often
occurs during contact sports. The blood vessels of the
limb are damaged. They swell and leak, causing
inflammation. Fluid builds up in the area contained
by the fascia. A fasciotomy is done to relieve this
pressure and prevent tissue death. Similar injury
occurs in high voltage electrical burns where deep
tissue damage occurs.

KEY TERMS
Endoscope—A tube that contains a tiny camera and
light, that is inserted in the body to allow a doctor to
see inside without making a large incision.

20 minutes to one hour. The doctor makes two small
incisions on either side of the heel. An endoscope is
inserted in one to guide the doctor in where to cut. A
tiny knife is inserted in the other. A portion of the
fascia is cut from near the heel; then the incisions are
closed.

Preparation
Little preparation is done before a fasciotomy.
When the fasciotomy is related to burn injuries, the
fluid and electrolyte status of the patient are constantly monitored.

Aftercare
Aftercare depends on the reason for the fasciotomy. People who have endoscopic plantar fasciotomy can walk without pain almost immediately,
return to wearing their regular shoes within three
to five days, and return to normal activities within
three weeks. Most will need to wear arch supports in
their shoes.

Risks
Precautions
In the case of injury, fasciotomy is done on an
emergency basis, and the outcome of the surgery
depends largely on the general health of the patient.
Plantar fasciotomies are appropriate for most people
whose foot problems cannot be resolved in any
other way.

In endoscopic plantar fasciotomy, the greatest
risk is that the arch will drop slightly as a result of
this surgery, causing other foot problems. Risks
involved with other types of fasciotomy are those
associated with the administration of anesthesia and
the development of blood clots.

Normal results
Description
Fasciotomy in the limbs is usually done by a
surgeon under general or regional anesthesia. An
incision is made in the skin, and a small area of fascia
is removed where it will best relieve pressure. Then the
incision is closed.
Plantar fasciotomy is an endoscopic (performed
with the use of an endoscope) procedure. It is done by
a foot specialist in a doctor’s office or outpatient
surgical clinic under local anesthesia and takes
1438

Fasciotomy in the limbs reduces pressure, thus
reducing tissue death. Endoscopic plantar fasciotomy
has a success rate of 90–95%.
Resources
OTHER

‘‘New Treatments for Heel Spur Syndrome.’’ <http://
www.footspecialist.com/heelspur.html>.

Tish Davidson, A.M.
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Fasting is voluntarily not eating food for varying
lengths of time. Fasting is used as a medical therapy
for many conditions. It is also a spiritual practice in
many religions.

Purpose
Fasting can be used for nearly every chronic condition, including allergies, anxiety, arthritis, asthma,
depression, diabetes, headaches, heart disease, high
cholesterol, low blood sugar, digestive disorders, mental illness, and obesity. Fasting is an effective and safe
weight loss method. It is frequently prescribed as a
detoxification treatment for those with conditions
that may be influenced by environmental factors,
such as cancer and multiple chemical sensitivity.
Fasting has been used successfully to help treat people
who have been exposed to high levels of toxic materials due to accident or occupation. Fasting is thought
to be beneficial as a preventative measure to increase
overall health, vitality, and resistance to disease.
Fasting is also used as a method of mental and spiritual rejuvenation.

Description
Origins
Used for thousands of years, fasting is one of the
oldest therapies in medicine. Many of the great doctors of ancient times and many of the oldest healing
systems have recommended it as an integral method of
healing and prevention. Hippocrates, the father of
Western medicine, believed fasting enabled the body
to heal itself. Paracelsus, another great healer in the
Western tradition, wrote 500 years ago that ‘‘fasting is
the greatest remedy, the physician within.’’ Ayurvedic
medicine, the world’s oldest healing system, has long
advocated fasting as a major treatment.

The principle of fasting is simple. When the intake
of food is temporarily stopped, many systems of the
body are given a break from the hard work of digestion. The extra energy gives the body the chance to
heal and restore itself, and burning stored calories gets
rid of toxic substances stored in the body.
The digestive tract is the part of the body most
exposed to environmental threats, including bacteria,
viruses, parasites, and toxins. It requires the most
immune system support. When food is broken down
in the intestines, it travels through the blood to the
liver, the largest organ of the body’s natural detoxification system. The liver breaks down and removes the
toxic by-products produced by digestion, including
natural ones and the chemicals now present in the
food supply. During fasting, the liver and immune
system are essentially freed to detoxify and heal other
parts of the body.
Many healers claim that fasting is a particularly
useful therapy for Americans and for the modern
lifestyle, subjected to heavy diets, overeating, and
constant exposure to food additives and chemicals.
Some alternative practitioners have gone so far as to
estimate that the average American is carrying 5-10
pounds of toxic substances in their bodies, for which
fasting is the quickest and most effective means of
removal.
Physiology of fasting

Fasting has also been used in nearly every religion
in the world, including Christianity, Judaism,
Buddhism, and Islam. Many of history’s great
spiritual leaders fasted for mental and spiritual
clarity, including Jesus, Buddha, and Mohammed. In
one of the famous political acts of the last century, the
Indian leader Mahatma Gandhi fasted for 21 days
to promote peace.

Through evolution, the body became very efficient at storing energy and handling situations when
no food was available. For many centuries, fasting was
probably a normal occurrence for most people, and
the body adapted to it. It is estimated that even very
thin people can survive for 40 days or more without
food. The body has a special mechanism that is
initiated when no food is eaten. Fasting is not starvation, but rather the body’s burning of stored energy.
Starvation occurs when the body no longer has any
stored energy and begins using essential tissues such as
organs for an energy source. Therapeutic fasts are
stopped long before this happens.

Fasting has been used in Europe as a medical
treatment for years. Many spas and treatment centers,
particularly those in Germany, Sweden, and Russia,

Many physiological changes occur in the body
during fasting. During the first day or so, the body
uses its glycogen reserves, the sugars that are the basic

GALE ENCYCLOPEDIA OF MEDICINE

1439

Fasting

Fasting

use medically supervised fasting. Fasting has gained
popularity in American alternative medicine over the
past several decades, and many doctors feel it is
beneficial. Fasting is a central therapy in detoxification, a healing method founded on the principle
that the build up of toxic substances in the body is
responsible for many illnesses and conditions.

Fasting

energy supply. After these are depleted, the body
begins using fat. However, the brain, which has high
fuel requirements, still needs glucose (sugars converted
from glycogen). To obtain glucose for the brain, the
body begins to break down muscle tissue during the
second day of the fast. Thus, during fasting some
muscle loss will occur. To fuel the brain, the body
would need to burn over a pound of muscle a day,
but the body has developed another way to create
energy that saves important muscle mass. This
protein-sparing process is called ketosis, which occurs
during the third day of a fast for men and the second
day for women. In this highly efficient state, the liver
begins converting stored fat and other nonessential
tissues into ketones, which can be used by the brain,
muscles, and heart as energy. It is at this point in the
fast that sensations of hunger generally go away, and
many people experience normal or even increased
energy levels. Hormone levels and certain functions
become more stable in this state as well. The goal of
most fasts is to allow the body to reach the ketosis
state in order to burn excess fat and unneeded or
damaged tissue. Thus, fasts longer than three days
are generally recommended as therapy.
Weight loss occurs most rapidly during the first
few days of a fast, up to 2 pounds per day. In following
days, the figure drops to around 0.5 pound per day.
An average weight loss of a pound a day for an entire
fast can be expected.
Performing a fast
Fasts can be performed for varying lengths of
time, depending on the person and his or her health
requirements. For chronic conditions, therapists
recommend from two to four weeks to get the most
benefits. Seven-day fasts are also commonly performed. A popular fasting program for prevention
and general health is a three-day fast taken four
times per year, at the change of each season. These
can be easily performed over long weekends.
Preventative fasts of one day per week are used by
many people as well.
Juice fasts are also used by many people,
although these are not technically fasts. Juice fasts
are less intensive than water fasts because the body
doesn’t reach the ketosis stage. The advantage of
juice fasts is that fruit and vegetable drinks can
supply extra energy and nutrients. People can fit a
few days of juice fasting into their normal schedules
without significant drops in energy. Juice fasts are
also said to have cleansing and detoxifying effects.
The disadvantage of juice fasts is that the body never
gets to the ketosis stage, so these fasters are thought
1440

to lack the deep detoxification and healing effects of
the water fast.
Medical supervision is recommended for any
fast over three days. Most alternative medicine practitioners, such as homeopaths, naturopathic doctors,
and ayurvedic doctors, can supervise and monitor
patients during fasts. Those performing extended
fasts and those with health conditions may require
blood, urine, and other tests during fasting. There
are many alternative health clinics that perform
medically supervised fasts as well. Some conventional medical doctors may also supervise patients
during fasts. Costs and insurance coverage vary,
depending on the doctor, clinic, and requirements
of the patient.

Preparations
Fasts must be entered and exited with care. To
enter a fast, the diet should be gradually lightened over
a few days. First, heavy foods such as meats and dairy
products should be eliminated for a day or two.
Grains, nuts, and beans should then be reduced for
several days. The day before a fast, only easily digested
foods like fruits, light salads, and soups should be
eaten. During the fast, only pure water and occasional
herbal teas should be drunk.
Fasts should be ended as gradually as they are
entered, going from lighter to heavier foods progressively. The diet after a fast should emphasize fresh,
wholesome foods. Fasters should particularly take
care not to overeat when they complete a fast.

Precautions
Fasting isn’t appropriate for everyone and, in
some cases, could be harmful. Any person undertaking a first fast longer than three days should seek
medical supervision. Those with health conditions
should always have medical support during fasting.
Plenty of water should be taken by fasters since
dehydration can occur. Saunas and sweating therapies are sometimes recommended to assist detoxification, but should be used sparingly. Those fasting
should significantly slow down their lifestyles.
Taking time off of work is helpful, or at least
reducing the work load. Fasters should also get
plenty of rest. Exercise should be kept light, such as
walking and gentle stretching.

Side effects
Those fasting may experience side effects of
fatigue, malaise, aches and pains, emotional duress,
GALE ENCYCLOPEDIA OF MEDICINE

Ayurvedic medicine—A traditional healing system
developed in India.
Toxin—A substance that has poisonous effects on
the body.

Fatigue

KEY TERMS

Fatigue
Definition
Fatigue is physical and/or mental exhaustion that
can be triggered by stress, medication, overwork, or
mental and physical illness or disease.

Description
acne, headaches, allergies, swelling, vomiting, bad
breath, and symptoms of colds and flu. These reactions are sometimes called healing crises, which are
caused by temporarily increased levels of toxins in
the body due to elimination and cleansing. Lower
energy levels should be expected during a fast.

Research and general acceptance
The physiology of fasting has been widely studied
and documented by medical science. Beneficial effects
such as lowered cholesterol and improved general
functioning have been shown. Fasting as a treatment
for illness and disease has been studied less, although
some studies around the world have shown beneficial
results. A 1984 study showed that workers in Taiwan
who had severe chemical poisoning had dramatic
improvement after a ten-day fast. In Russia and
Japan, studies have demonstrated fasting to be an
effective treatment for mental illness. Fasting has
been featured on the cover of medical journals,
although mainstream medicine has generally ignored
fasting and detoxification treatments as valid medical
procedures.
The majority of research that exists on fasting is
testimonial, consisting of individual personal accounts
of healing without statistics or controlled scientific
experiments. In the alternative medical community,
fasting is an essential and widely accepted treatment
for many illnesses and chronic conditions.
Resources
ORGANIZATIONS

Fasting Center International. 32 West Anapurna St.,
#360, Santa Barbara, CA 93101. <http://
www.fasting.com>.

Douglas Dupler, MA

Fasting blood sugar test see Blood sugar tests
Fasting plasma glucose test see Blood sugar
tests
GALE ENCYCLOPEDIA OF MEDICINE

Everyone experiences fatigue occasionally. It is
the body’s way of signaling its need for rest and
sleep. But when fatigue becomes a persistent feeling
of tiredness or exhaustion that goes beyond normal
sleepiness, it is usually a sign that something more
serious is amiss.
Physically, fatigue is characterized by a profound
lack of energy, feelings of muscle weakness, and slowed movements or central nervous system reactions.
Fatigue can also trigger serious mental exhaustion.
Persistent fatigue can cause a lack of mental clarity
(or feeling of mental ‘‘fuzziness’’), difficulty concentrating, and in some cases, memory loss.

Causes and symptoms
Fatigue may be the result of one or more environmental causes such as inadequate rest, improper
diet, work and home stressors, or poor physical conditioning, or one symptom of a chronic medical
condition or disease process in the body. Heart disease, low blood pressure, diabetes, end-stage renal
disease, iron-deficiency anemia, narcolepsy, and
cancer can cause long-term, ongoing fatigue symptoms. Acute illnesses such as viral and bacterial
infections can also trigger temporary feelings of
exhaustion. In addition, mental disorders such as
depression can also cause fatigue.
A number of medications, including antihistamines, antibiotics, and blood pressure medications,
may cause drowsiness as a side-effect. Individuals
already suffering from fatigue who are prescribed
one of these medications may wish to check with
their healthcare provider about alternative
treatments.
Extreme fatigue which persists, unabated, for at
least six months, is not the result of a diagnosed
disease or illness, and is characterized by flu-like
symptoms such as swollen lymph nodes, sore throat,
and muscle weakness and/or pain may indicate a
diagnosis of chronic fatigue syndrome. Chronic fatigue
syndrome (sometimes called chronic fatigue immune
deficiency syndrome), is a debilitating illness that
1441

Fatigue

causes overwhelming exhaustion and a constellation
of neurological and immunological symptoms.
Between 1.5 and 2 million Americans are estimated
to suffer from the disorder.

Diagnosis
Because fatigue is a symptom of a number of
different disorders, diseases, and lifestyle choices,
diagnosis may be difficult. A thorough examination
and patient history by a qualified healthcare provider
is the first step in determining the cause of the fatigue.
A physician can rule out physical conditions and
diseases that feature fatigue as a symptom, and can
also determine if prescription drugs, poor dietary
habits, work environment, or other external stressors
could be triggering the exhaustion. Several diagnostic
tests may also be required to rule out common physical causes of exhaustion, such as blood tests to check
for iron-deficiency anemia.
Diagnosis of chronic fatigue syndrome is significantly more difficult. Because there is no specific
biological marker or conclusive blood test to check
for the disorder, healthcare providers must rely on
the patient’s presentation and severity of symptoms
to make a diagnosis. In many cases, individuals with
chronic fatigue syndrome go through a battery of
invasive diagnostic tests and several years of consultation with medical professionals before receiving a
correct diagnosis.

Treatment
Conventional medicine recommends the dietary
and lifestyle changes outlined above as a first line of
defense against fatigue. Individuals who experience
occasional fatigue symptoms may benefit from
short term use of caffeine-containing central nervous
stimulants, which make people more alert, less
drowsy, and improve coordination. However, these
should be prescribed with extreme caution, as overuse of the drug can lead to serious sleep disorders, like
insomnia.
Another reason to avoid extended use of caffeine
is its associated withdrawal symptoms. People who use
large amounts of caffeine over long periods build up a
tolerance to it. When that happens, they have to use
more and more caffeine to get the same effects.
Heavy caffeine use can also lead to dependence. If an
individual stops using caffeine abruptly, withdrawal
symptoms may occur, including headache, fatigue,
drowsiness, yawning, irritability, restlessness, vomiting, or runny nose. These symptoms can go on for as
long as a week.
1442

Alternative treatment
The treatment of fatigue depends on its direct
cause, but there are several commonly prescribed
treatments for non-specific fatigue, including dietary
and lifestyle changes, the use of essential oils and
herbal therapies, deep breathing exercises, traditional
Chinese medicine, and color therapy.
Dietary changes
Inadequate or inappropriate nutritional intake
can cause fatigue symptoms. To maintain an adequate
energy supply and promote overall physical wellbeing, individuals should eat a balanced diet and
observe the following nutritional guidelines:


Drinking plenty of water. Individuals should try to
drink 9 to 12 glasses of water a day. Dehydration can
reduce blood volume, which leads to feelings of
fatigue.



Eating iron-rich foods (i.e., liver, raisins, spinach,
apricots). Iron enables the blood to transport oxygen
throughout the tissues, organs, and muscles, and
diminished oxygenation of the blood can result in
fatigue.



Avoiding high-fat meals and snacks. High fat foods
take longer to digest, reducing blood flow to the
brain, heart, and rest of the body while blood flow
is increased to the stomach.



Eating unrefined carbohydrates
together for sustained energy.



Balancing proteins. Limiting protein to 15-20 grams
per meal and two snacks of 15 grams is recommended, but not getting enough protein adds to
fatigue. Pregnant or breastfeeding women should
get more protein.



Getting the recommended daily allowance of B complex vitamins (specifically, pantothenic acid, folic
acid, thiamine, and vitamin B12). Deficiencies in
these vitamins can trigger fatigue.



Getting the recommended daily allowance of
selenium, riboflavin, and niacin. These are all
essential nutritional elements in metabolizing food
energy.



Controlling portions. Individuals should only eat
when they’re hungry, and stop when they’re full.
An overstuffed stomach can cause short-term
fatigue, and individuals who are overweight are
much more likely to regularly experience fatigue
symptoms.

and

proteins

GALE ENCYCLOPEDIA OF MEDICINE

Lifestyle factors such as a high-stress job, erratic
work hours, lack of social or family support, or erratic
sleep patterns can all cause prolonged fatigue. If stress
is an issue, a number of relaxation therapies and
techniques are available to help alleviate tension,
including massage, yoga, aromatherapy, hydrotherapy,
progressive relaxation exercises, meditation, and
guided imagery. Some individuals may also benefit
from individual or family counseling or psychotherapy sessions to work through stress-related fatigue
that is a result of family or social issues.
Maintaining healthy sleep patterns is critical to
proper rest. Having a set ‘‘bedtime’’ helps to keep
sleep on schedule. A calm and restful sleeping environment is also important to healthy sleep. Above all,
the bedroom should be quiet and comfortable,
away from loud noises and with adequate window
treatments to keep sunlight and streetlights out.
Removing distractions from the bedroom such as
televisions and telephones can also be helpful.
Essential oils
Aromatherapists, hydrotherapists, and other
holistic healthcare providers may recommend the use
of essential oils of rosemary (Rosmarinus officinalis),
eucalyptus blue gum (Eucalyptus globulus), peppermint, (Mentha x piperata), or scots pine oil (Pinus
sylvestris) to stimulate the nervous system and reduce
fatigue. These oils can be added to bathwater or
massage oil as a topical application. Citrus oils such
as lemon, orange, grapefruit, and lime have a similar
effect, and can be added to a steam bath or vaporizer
for inhalation.
Herbal remedies
Herbal remedies that act as circulatory stimulants
can offset the symptoms of fatigue in some individuals. An herbalist may recommend an infusion of
ginger (Zingiber officinale) root or treatment with
cayenne (Capsicum annuum), balmony (Chelone
glabra), damiana (Turnera diffusa), ginseng (Panax
ginseng), or rosemary (Rosmarinus officinalis) to treat
ongoing fatigue.
An infusion is prepared by mixing the herb with
boiling water, steeping it for several minutes, and then
removing the herb from the infusion before drinking.
A strainer, tea ball, or infuser can be used to immerse
loose herb in the boiling water before steeping and
separating it. A second method of infusion is to mix
the loose herbal preparation with cold water first,
bringing the mixture to a boil in a pan or teapot, and
GALE ENCYCLOPEDIA OF MEDICINE

then separating the tea from the infusion with a
strainer before drinking.
Caffeine-containing central nervous system
stimulants such as tea (Camellia senensis) and cola
(Cola nitida) can provide temporary, short-term relief
of fatigue symptoms. However, long-term use of
caffeine can cause restlessness, irritability, and other
unwanted side effects, and in some cases may actually
work to increase fatigue after the stimulating effects
of the caffeine wear off. To avoid these problems,
caffeine intake should be limited to 300 mg or less a
day (the equivalent of 4-8 cups of brewed, hot tea).
Traditional Chinese medicine
Chinese medicine regards fatigue as a blockage or
misalignment of qi, or energy flow, inside the human
body. The practitioner of Chinese medicine chooses
acupuncture and/or herbal therapy to rebalance the
entire system. The Chinese formula Minot
Bupleurum soup (or Xiao Chia Hu Tang) has been
used for nearly 2,000 years for the type of chronic
fatigue that comes after the flu. In this condition, the
person has low-grade fever, nausea, and fatigue. There
are other formulas that are helpful in other cases.
Acupuncture involves the placement of a series of
thin needles into the skin at targeted locations on the
body known as acupoints in order to harmonize the
energy flow within the human body.
Deep breathing exercises
Individuals under stress often experience fast,
shallow breathing. This type of breathing, known as
chest breathing, can lead to shortness of breath,
increased muscle tension, inadequate oxygenation of
blood, and fatigue. Breathing exercises can both
improve respiratory function and relieve stress and
fatigue.
Deep breathing exercises are best performed while
laying flat on the back on a hard surface, usually the
floor. The knees are bent, and the body (particularly
the mouth, nose, and face) is relaxed. One hand should
be placed on the chest and one on the abdomen to
monitor breathing technique. With proper breathing
techniques, the abdomen will rise further than the
chest. The individual takes a series of long, deep
breaths through the nose, attempting to raise the
abdomen instead of the chest. Air is exhaled through
the relaxed mouth. Deep breathing can be continued
for up to 20 minutes. After the exercise is complete, the
individual checks again for body tension and relaxation. Once deep breathing techniques have been mastered, an individual can use deep breathing at any time
1443

Fatigue

Lifestyle changes

Fatty liver

or place as a quick method of relieving tension and
preventing fatigue.
Color therapy
Color therapy, also known as chromatherapy, is
based on the premise that certain colors are infused
with healing energies. The therapy uses the seven colors
of the rainbow to promote balance and healing in the
mind and body. Red promotes energy, empowerment,
and stimulation. Physically, it is thought to improve
circulation and stimulate red blood cell production.
Red is associated with the seventh chakra, located at
the root; or base of spine. In yoga, the chakras are
specific spiritual energy centers of the body.
Therapeutic color can be administered in a number of ways. Practitioners of Ayurvedic, or traditional
Indian medicine, wrap their patients in colored cloth
chosen for its therapeutic hue. Individuals suffering
from fatigue would be wrapped in reds and oranges
chosen for their uplifting and energizing properties.
Patients may also be bathed in light from a color
filtered light source to enhance the healing effects of
the treatment.
Individuals may also be treated with color-infused
water. This is achieved by placing translucent red
colored paper or colored plastic wrap over and around
a glass of water and placing the glass in direct sunlight
so the water can soak up the healing properties and
vibrations of the color. Environmental color sources
may also be used to promote feelings of stimulation
and energy. Red wall and window treatments, furniture, clothing, and even food may be recommended for
their energizing healing properties.
Color therapy can be used in conjunction with
both hydrotherapy and aromatherapy to heighten
the therapeutic effect. Spas and holistic healthcare
providers may recommend red color baths or soaks,
which combine the benefits of a warm or hot water
soak with energizing essential oils and the fatiguefighting effects of bright red hues used in color
therapy.

Prognosis
Fatigue related to a chronic disease or condition
may last indefinitely, but can be alleviated to a degree
through some of the treatment options outlined
here. Exhaustion that can be linked to environmental
stressors is usually easily alleviated when those
stressors are dealt with properly.
There is no known cure for chronic fatigue
syndrome, but steps can be taken to lessen symptoms
1444

KEY TERMS
Aromatherapy—The therapeutic use of plantderived, aromatic essential oils to promote physical
and psychological well-being.
Guided imagery—The use of relaxation and mental
visualization to improve mood and/or physical
well-being.
Hydrotherapy—Hydrotherapy, or water therapy, is
use of water (hot, cold, steam, or ice) to relieve
discomfort and promote physical well-being.

and improve quality of life for these individuals while
researchers continue to seek a cure.

Prevention
Many of the treatments outlined above are also
recommended to prevent the onset of fatigue. Getting
adequate rest and maintaining a consistent bedtime
schedule are the most effective ways to combat fatigue.
A balanced diet and moderate exercise program are
also important to maintaining a consistent energy
level.
Resources
BOOKS

Davis, Martha, et al. The Relaxation & Stress Reduction
Workbook. 4th ed. Oakland, CA: New Harbinger
Publications, Inc., 1995.
Hoffman, David. The Complete Illustrated Herbal. New
York: Barnes & Noble Books, 1999.

Paula Anne Ford-Martin

Fatty liver
Definition
Fatty liver is the collection of excessive amounts
of triglycerides and other fats inside liver cells.

Description
Also called steatosis, fatty liver can be a temporary or long-term condition, which is not harmful itself,
but may indicate some other type of problem. Left
untreated, it can contribute to other illnesses. It is
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The most common cause of fatty liver in the
United States is alcoholism. In alcoholic fatty liver,
over consumption of alcohol changes the way that
the liver breaks down and stores fats. Often, people
with chronic alcoholism also suffer from malnutrition
by eating irregularly and not consuming a balanced
diet. Conditions that can also cause fatty liver are
other forms of malnutrition (especially when there
is not enough protein in the diet), obesity, diabetes
mellitus, and Reye’s syndrome in children. Pregnancy
can cause a rare, but serious form of fatty liver that
starts late in pregnancy and may be associated with
jaundice and liver failure. Some drug overdoses or
toxic chemical poisonings, such as carbon tetrachloride, can also cause fatty liver.
Often, there are no symptoms associated with fatty
liver. If there are symptoms, they can include pain
under the rib cage on the right side of the body, swelling
of the abdomen, jaundice, and fever. Symptoms that
occur less often in alcoholic fatty liver, but more often
in pregnancy related fatty liver, are nausea, vomiting,
loss of appetite, and abdominal pain.

Diagnosis
During a physical examination, a doctor might
notice that the liver is enlarged and tender when the
abdomen is palpated (examined with the tips of the
fingers while the patient lies flat). Blood tests may be
used to determine if the liver is functioning properly. A
liver biopsy, where a small sample of liver tissue is
removed with a long needle or though a very small
incision, can be used to confirm fatty liver. In pregnant
women, the fatty liver condition is usually associated
with another serious complication, pre-eclampsia or
eclampsia. In this condition, the mother has seriously
high blood pressure, swelling, and possibly, seizures.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Jaundice—A condition where the skin and whites
of the eyes take on a yellowish color due to an
increase of bilirubin (a compound produced by
the liver) in the blood.
Reye’s syndrome—A serious, life-threatening illness in children, usually developing after a bout
of flu or chickenpox, and often associated with
the use of aspirin. In fatal cases, there is evidence
of accumulation of fat in the liver.
Triglycerides—A type of fat consumed in the diet
and produced by and stored in the body as an
energy source.

Laboratory abnormalities include elevations of the
SGOT (serum glutamic-oxaloacetic transaminase)
and SGPT (serum glutamic pyruvic transaminase).
In many cases the alkaline phosphatase will be significantly elevated due to cholestasis produced by the fatty
infiltration.

Treatment
Treatment involves correcting the condition that
caused fatty liver and providing supportive care. In
fatty liver caused by alcoholism, the treatment is to
give up drinking alcohol and to eat a healthy, well
balanced diet. In fatty liver associated with pregnancy,
the recommended treatment is to deliver the baby, if
the pregnancy is far enough along. Vitamin and
mineral supplements along with nutritional support
may be useful.

Prognosis
Fatty liver is usually reversible if recognized and
treated. There may be some long-term tendency
toward other types of liver problems depending on
how long and how severe the fatty liver condition
was. In pregnant women with the condition, the situation can be life threatening for both the mother and the
infant. Left untreated, there is a high risk of death for
both the mother and baby. Severe liver damage that
may require a liver transplant can occur in the mother
if the condition is not recognized early.

Prevention
Prevention consists of maintaining a well
balanced diet and healthy lifestyle with moderate or
1445

Fatty liver

usually reversible once the cause of the problem is
diagnosed and corrected. The liver is the organ
responsible for changing fats eaten in the diet to
types of fat that can be stored and used by the body.
Triglycerides are one of the forms of fat stored by the
body and used for energy and new cell formation.
The break down of fats in the liver can be disrupted
by alcoholism, malnutrition, pregnancy, or poisoning.
In fatty liver, large droplets of fat, containing mostly
triglycerides, collect within cells of the liver. The
condition is generally not painful and may go unnoticed for a long period of time. In severe cases, the liver
can increase to over three times its normal size and
may be painful and tender.

Fecal incontinence

no alcohol consumption. Pregnant women require
good prenatal care so that symptoms can be recognized and treated as early as possible. To prevent
Reye’s syndrome, children should not be given aspirin
to treat symptoms of the flu or other viruses.
Resources
PERIODICALS

Everson, Gregory T. ‘‘Liver Problems in Pregnancy: Part 2,
Managing Pre-Existing and Pregnancy-Induced Liver
Disease.’’ Medscape Women’s Health 3, no. 2 (1998).

Altha Roberts Edgren

Febrile agglutination tests see Fever evaluation tests
Fecal fat test see Stool fat test

Fecal incontinence
Definition
Fecal incontinence is the inability to control the
passage of gas or stools (feces) through the anus.
For some people fecal incontinence is a relatively
minor problem, as when it is limited to a slight
occasional soiling of underwear, but for other people
it involves a considerable loss of bowel control and has
a devastating effect on quality of life and psychological
well-being. Fortunately, professional medical treatment is usually able to restore bowel control or at
least substantially reduce the severity of the condition.

Description
Fecal incontinence, also called bowel incontinence, can occur at any age, but is most common
among people over the age of 65, who sometimes
have to cope with urinary incontinence as well. It was
reported in 1998 that about 2% of adults experience
fecal incontinence at least once a week whereas for
healthy independent adults over the age of 65 the
figure is about 7%. An extensive American survey,
published in 1993, found fecal soiling in 7.1% of the
surveyed population, with gross incontinence in 0.7%.
For men and women the incidence of soiling was the
same, but women were almost twice as likely to suffer
from gross incontinence.
The wider public health impact of fecal incontinence is considerable. In the United States, more than
1446

$400 million is spent each year on disposable underwear and other incontinence aids. Fecal incontinence
is the second most common reason for seeking a nursing home placement. One-third of the institutionalized elderly suffer from this condition. Incontinence
sufferers, however, often hesitate to ask their doctors
for help because they are embarrassed or ashamed.
The 1993 American survey discovered that only onesixth of those experiencing soiling had sought medical
advice, and only one-half of those afflicted with gross
incontinence.

Causes and symptoms
Fecal incontinence can result from a wide variety
of medical conditions, including childbirth-related
anal injuries, other causes of damage to the anus or
rectum, and nervous system problems.
Vaginal-delivery childbirth is a major cause of
fecal incontinence. In many cases, childbirth results
in damage to the anal sphincter, which is the ring
of muscle that closes the anus and keeps stools
within the rectum until a person can find an appropriate opportunity to defecate. Nerve injuries
during childbirth may also be a factor in some
cases. An ultrasound study of first-time mothers
found sphincter injuries in 35%. About one-third of
the injured women developed fecal incontinence or
an uncontrollable and powerful urge to defecate
(urgency) within six weeks of giving birth.
Childbirth-related incontinence is usually restricted
to gas, but for some women involves the passing of
liquid or solid stools.
The removal of hemorrhoids by surgery or other
techniques (hemorrhoidectomies) can also cause anal
damage and fecal incontinence, as can more complex
operations affecting the anus and surrounding areas.
Anal and rectal infections as well as Crohn’s disease
can lead to incontinence by damaging the muscles that
control defecation. For some people, incontinence
becomes a problem when the anal muscles begin to
weaken in midlife or old age.
Dementia, mental retardation, strokes, brain
tumors, multiple sclerosis, and other conditions
that affect the nervous system can cause fecal incontinence by interfering with muscle function or the
normal rectal sensations that trigger sphincter
contraction and are necessary for bowel control.
One study of multiple sclerosis patients discovered
that about half were incontinent. Nerve damage
caused by long-lasting diabetes mellitus (diabetic
neuropathy) is another condition that can give rise
to incontinence.
GALE ENCYCLOPEDIA OF MEDICINE

Medical assessments in cases of fecal incontinence
typically involve three steps: asking questions about
the patient’s past and current health (the medical
history); a physical examination of the anal region;
and testing for objective information regarding anal
and rectal function.
Patient history
The medical history relies on questions that allow
the doctor to evaluate the nature and severity of the
problem and its effect on the patient’s life. The doctor
asks, for instance, how long the patient has been
suffering from incontinence; how often and under
what circumstances incontinence occurs; whether the
patient has any control over defecation; and whether
the patient has obstacles to defecation in his or her
everyday surroundings, such as a toilet that can be
reached only by climbing a long flight of stairs.
For women who have given birth, a detailed obstetric
history is also necessary.
Physical examination
The physical examination begins with a visual
inspection of the anus and the area lying between the
anus and the genitals (the perineum) for hemorrhoids,
infections, and other conditions that might explain
the patient’s difficulties. During this phase of the
examination the doctor asks the patient to bear
down. Bearing down enables the doctor to check
whether rectal prolapse or certain other problems
exist. Rectal prolapse means that the patient’s rectum
has been weakened and drops down through the anus.
Next, the doctor uses a pin or probe to stroke the
perianal skin. Normally this touching causes the anal
sphincter to contract and the anus to pucker; if it does
not, nerve damage may be present. The final phase
of the examination requires the doctor to examine
internal structures by carefully inserting a gloved and
lubricated finger into the anal canal. This allows the
doctor to judge the strength of the anal sphincter and a
key muscle (the puborectalis muscle) in maintaining
continence; to look for abnormalities such as scars and
rectal masses; and to learn many other things about
the patient’s medical situation. At this point the doctor
performs the anal wink test again and asks the patient
to squeeze and bear down.
Laboratory tests
Information from the medical history and physical examination usually needs to be supplemented by
tests that provide objective measurements of anal and
GALE ENCYCLOPEDIA OF MEDICINE

rectal function. Anorectal manometry, a common
procedure, involves inserting a small tube (catheter)
or balloon device into the anal canal or rectum.
Manometry measures, among other things, pressure
levels in the anal canal, rectal sensation, and anal and
rectal reflexes. Tests are also available for assessing
nerve damage. An anal ultrasound probe can supply
accurate images of the anal sphincter and reveal
whether injury has occurred. Magnetic resonance
imaging, which requires the insertion of a coil into
the anal canal, is useful at times.

Treatment
Fecal incontinence arising from an underlying
condition such as diabetic neuropathy can sometimes
be helped by treating the underlying condition. When
that does not work, or no underlying condition can be
discovered, one approach is to have the patient use a
suppository or enema to stimulate defecation at the
same time every day or every other day. The goal is to
restore regular bowel habits and keep the bowels free
of stools. Medications such as loperamide (Imodium)
and codeine phosphate are often effective in halting
incontinence, but only in less severe cases involving
liquid stools or urgency. Dietary changes and exercises
done at home to strengthen the anal muscles may
also help.
Good results have been reported for biofeedback
training, although the subject has not been properly
researched. In successful cases, patients regain
complete control over defecation, or at least improve
their control, by learning to contract the external
part of the anal sphincter whenever stools enter the
rectum. All healthy people have this ability.
Biofeedback training begins with the insertion into
the rectum of a balloon manometry device hooked
up to a pressure monitor. The presence of stools in
the rectum is simulated by inflating the balloon,
which causes pressure changes that are recorded on
the monitor. The monitor also records sphincter
contraction. By watching the monitor and following
instructions from the equipment operator, the
patient gradually learns to contract the sphincter
automatically in response to fullness in the rectum.
Sometimes one training session is enough, but often
several are needed. Biofeedback is not an appropriate treatment in all cases, however. It is used only
with patients who are highly motivated; who are
able, to some extent, to sense the presence of stools
in the rectum; and who have not lost all ability to
contract the external anal sphincter. One specialist
suggests that possibly two-thirds of incontinence
sufferers are candidates for biofeedback.
1447

Fecal incontinence

Diagnosis

Fecal occult blood test

Resources

KEY TERMS
Anus—The opening at the lower end of the rectum.
Colostomy—A surgical procedure in which an
opening is made in the wall of the abdomen to
allow a part of the large intestine (the colon) to
empty outside the body.
Crohn’s disease—A disease marked by inflammation of the intestines.
Defecation—Passage of stools through the anus.

ORGANIZATIONS

International Foundation for Functional Gastrointestinal
Disorders. PO Box 17864, Milwaukee, WI 53217. (888)
964-2001. <http://www.iffgd.org>.
National Association for Continence. PO Box 8310,
Spartanburg, SC 29305-8310. (800) 252-3337. <http://
www.nafc.org>.
National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.

Hemorrhoids—Enlarged veins in the anus or rectum. They are sometimes associated with fecal
incontinence.
Rectum—The lower section of the large intestine
that holds stools before defecation.

Howard Baker

Fecal lipids test see Stool fat test

Sphincter—A circular band of muscle that surrounds and encloses an opening to the body or to
one of its hollow organs. Damage to the sphincter
surrounding the anus can cause fecal incontinence.
Stools—Undigested food and other waste that is
eliminated through the anus.
Suppository—A solid medication that slowly dissolves after being inserted into the rectum or other
body cavity.

Some people may require surgery. Sphincter
damage caused by childbirth is often effectively treated with surgery, however, as are certain other kinds of
incontinence-related sphincter injuries. Sometimes
surgical treatment requires building an artificial
sphincter using a thigh muscle (the gracilis muscle).
At one time a colostomy was necessary for severe cases
of incontinence, but is now rarely performed.

Prognosis
Fecal incontinence is a problem that usually
responds well to professional medical treatment, even
among elderly and institutionalized patients. If
complete bowel control cannot be restored, the impact
of incontinence on everyday life can still be lessened
considerably in most cases. When incontinence
remains a problem despite medical treatment, disposable underwear and other commercial incontinence
products are available to make life easier. Doctors and
nurses can offer advice on coping with incontinence,
and people should never be embarrassed about
seeking their assistance. Counseling and information
are also available from support groups.
1448

Fecal occult blood test
Definition
The fecal occult blood test (FOBT) is performed
as part of the routine physical examination during the
examination of the rectum. It is used to detect microscopic blood in the stool and is a screening tool for
colorectal cancer.

Purpose
FOBT uses chemical indicators on stool samples
to detect the presence of blood not otherwise visible.
(The word ‘‘occult’’ in the test’s name means that
the blood is hidden from view.) Blood originating
from or passing through the gastrointestinal tract
can signal many conditions requiring further diagnostic procedures and, possibly, medical treatment. These
conditions may be benign or malignant and some of
them include:


colon cancer, rectal cancer, and gastric cancers



ulcers



hemorrhoids



polyps



inflammatory bowel disease



irritations or lesions of the gastrointestinal tract
caused by medications (such as nonsteroidal antiinflammatory drugs, also called NSAIDs)



irritations or lesions of the gastrointestinal tract
caused by stomach acid disorders, such as reflux
esophagitis
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Certain foods and medicines can influence the test
results. Some fruits contain chemicals that prevent the
guaiac, the chemical in which the test paper is soaked,
from reacting with the blood. Aspirin and some
NSAIDs irritate the stomach, resulting in bleeding,
and should be avoided prior to the examination.
Red meat and many vegetables and fruits containing
vitamin C also should be avoided for a specified period
of time before the test. All of these factors could
result in a false-positive result.

Description
Feces for the stool samples is obtained either by
the physician at the rectal examination or by the
patient at home, using a small spatula or a collection
device. In most cases, the collection of stool samples
can easily be done at home, using a kit supplied by the
physician. The standard kit contains a specially
prepared card on which a small sample of stool will
be spread, using a stick provided in the kit. The sample
is placed in a special envelope and either mailed or
brought in for analysis. When the physician applies
hydrogen peroxide to the back of the sample, the
paper will turn blue if an abnormal amount of blood
is present.
Types of fecal occult blood tests
Hemoccult is the most commonly used fecal
occult blood test. The Hemoccult test takes less than
five minutes to perform and may be performed in the
physician’s office or in the laboratory. The Hemoccult
blood test can detect bleeding from the colon as low as
0.5 mg per day.
Tests that use anti-hemoglobin antibodies (or
immunochemical tests) to detect blood in the stool
are also used. Immunochemical tests can detect up to
0.7 mg of hemoglobin in the stool and do not require
dietary restrictions. Immunochemical tests

Hemoquant, another fecal occult blood test, is
used to detect as much as 500 mg/g of blood in the
stool. Like the Hemoccult, the Hemoquant test is
affected by red meat. It is not affected by chemicals
in vegetables.
Fecal blood may also be measured by the amount
of chromium in the red blood cells in the feces. The
stool is collected for three to ten days. The test is used
in cases where the exact amount of blood loss
required. It is the only test that can exclude blood
loss from the gastrointestinal area with accuracy.
Medicare coverage began on January 1, 2004, for
a newer fecal occult blood test based on immunoassay.
This technique does not rely on guiaic, so it is not
influenced by diet or medications used prior to the
test. The immunoassay test also requires fewer specimen collections. At a conference of gastroenterologists ( physicians who specialize in diseases of the
stomach and related digestive systems), a company
announced a new fecal occult blood test that was
based on DNA and appeared more sensitive than
traditional tests. Widespread use of these new tests
remains to be seen; the traditional guiaic test has
been in place for about 30 years.

Preparation
For 72 hours prior to collecting samples, patients
should avoid red meats, NSAIDs (including aspirin),
antacids, steroids, iron supplements, and vitamin C,
including citrus fruits and other foods containing
large amounts of vitamin C. Foods like uncooked
broccoli, uncooked turnips, cauliflower, uncooked
cantaloupe, uncooked radish and horseradish and
parsnips should be avoided and not eaten during the
72 hours prior to the examination. Fish, chicken,
pork, fruits (other than melons) and many cooked
vegetables are permitted in the diet.

Results
Many factors can result in false-positive and falsenegative findings.
Positive results



are not accurate for screening for stomach cancer



are more sensitive than Hemoccult tests in detecting
colorectal cancer



are more expensive than Hemoccult tests.

It is important to note that a true-positive finding
only signifies the presence of blood—it is not an indication of cancer. The National Cancer Institute states
that, in its experience, less than 10% of all positive
results were caused by cancer. The FOBT is positive in
1–5% of the unscreened population and 2–10% of
those are found to have cancer. The physician will
want to follow up on a positive result with further

GALE ENCYCLOPEDIA OF MEDICINE

1449

Fecal occult blood test

The FOBT is used routinely (in conjunction with a
rectal examination performed by a physician) to
screen for colorectal cancer, particularly after age 50.
The ordering of this test should not be taken as an
indication that cancer is suspected. The FOBT must be
combined with regular screening endoscopy (such as a
sigmoidoscopy) to detect cancers at an early stage.

Feldenkrais method

OTHER

KEY TERMS
Occult—Not visible or easily detected.

‘‘Colon and Rectum Cancer.’’ American Cancer Society.
2000. July 10, 2001. <http://www.cancer.org>.
‘‘Colorectal Cancer Screening.’’WebMD. <http://
my.webmd.com/content/article/2955.291>.
‘‘Fecal Occult Bood Test.’’ Virtual Health Fair. July 10,
2001. <http://vfair.com/resources/lab/fecal.htm>.

tests, as indicated by other factors in the patient’s
history or condition.

Jill S. Lasker
Cheryl Branche, M.D.
Teresa G. Odle

Negative results
Alternatively, a negative result (meaning no blood
was detected) does not guarantee the absence of colon
cancer, which may bleed only occasionally or not at
all. (Only 50% of colon cancers are FOBT-positive.)
Conclusions
Screening using the FOBT has been demonstrated to reduce colorectal cancer. However,
because only half of colorectal cancers are FOBTpositive, FOBT must be combined with regular
screening endoscopy to increase the detection of
pre-malignant colorectal polyps and cancers. Since,
through FOBT, cancer may be detected early, the
benefits of possible early detection must be considered along with the likelihood of complications and
costs for additional studies.
Resources
BOOKS

DeVita, Vincent, Samuel Hellman, and Steven Rosenburg.
Cancer: Principles and Practices of Oncology.
Philadelphia: Lippincott Williams & Wilkins, 2001.
Yamada, Tadetaka, editor. Textbook of Gastroenterology
Volumes One and Two. Philadelphia: Lippincott
Williams & Wilkins, 2001.
PERIODICALS

‘‘DNA-based Stool Test More Sensitive than Fecal Occult
Blood Test in Study.’’ Health & Medicine Week
November 10, 2003: 194.
From the Centers for Disease Control and
Prevention.‘‘Trends in Screening for Colorectal
Cancer—United States, 1997 and 1999.’’Journal of the
American Medical Association 28 (March 2001): 12.
Silverman, Jennifer. ‘‘Colorectal Screning Option.’’ Family
Practice News 33 (December 15, 2003): 49–51.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800)ACS-2345. <http://www.cancer.org>.
National Cancer Institute (National Institutes of Health).
9000 Rockville Pike, Bethesda, MD 20892. (800)
422-6237. <http://www.nci.nih.gov>.
1450

Feldenkrais method
Definition
The Feldenkrais method is an educational system
that allows the body to move and function more
efficiently and comfortably. Its goal is to re-educate
the nervous system and improve motor ability. The
system can accomplish much more, relieving pressure
on joints and weak points, and allowing the body to
heal repetitive strain injuries. Continued use of the
method can relieve pain and lead to higher standards
of achievement in sports, the martial arts, dancing and
other physical disciplines.
Pupils are taught to become aware of their movements and to become aware of how they use their
bodies, thus discovering possible areas of stress and
strain. The goal of Feldenkrais is to take the individual
from merely functioning, to functioning well, free of
pain and restriction of movement. Feldenkrais himself
stated that his goal was, ‘‘To make the impossible
possible, the possible easy, and the easy, elegant.’’

Purpose
This method of re-educating the nervous system
can be beneficial to a wide range of people, including
athletes, children, the elderly, martial artists, those
who are handicapped, people with special needs, and
those suffering from degenerative diseases. It has also
proved popular with artists, particularly musicians, a
number of whom have used Feldenkrais to improve
their performance.
The Feldenkrais Guild of North America
(FGNA) states that over half of the those who turn
to Feldenkrais practitioners are seeking relief from
pain. Many people who have pain from an injury
compensate by changing their movements to limit
pain. Often these changed movements remain after
GALE ENCYCLOPEDIA OF MEDICINE

Moshe Feldenkrais was born on the border between
Russia and Poland. When he was only a boy of 13, he
traveled to Palestine on foot. The journey took a year, and
once there, young Feldenkrais worked as a laborer and
cartographer, also tutoring others in mathematics.
Moving to France in 1933, he graduated in mechanical
and electrical engineering from the Ecole des Travaux
Publiques de Paris.
Feldendrais became the first person to open a Judo
center in Paris after meeting with Jigaro Kano. He was
also one of the first Europeans to become a black belt in
Judo, in 1936.
Obtaining his Ph.D. at the Sorbonne, he went on to
assist Nobel Prize laureate, Frédéric Joliot-Curie at the
Curie Institute. During World War II in England, he
worked on the new sonar anti-submarine research.
Prompted by a recurring leg injury, he applied his
knowledge of the martial arts and his training as an
engineer to devise a method of re-integrating the body.
The concept was that more efficient movement would
allow for the treatment of pain or disability, and the
better-functioning of the body as a whole. Later on,
he would begin to teach what he had learned to others
in Tel Aviv.
In addition to many books about judo, including
Higher Judo, he wrote six books on his method.

the pain from the original injury is gone, and new pain
may occur. Feldenkrais helps students become aware
of the changed movements and allows them to learn
new movements that relieve their pain. Apart from the
obvious physical benefits of more efficient movement
and freedom from pain and restriction, Feldenkrais
practitioners assert that there are other positive benefits for overall physical and mental health. Feldenkrais
can result in increased awareness, flexibility, and
coordination, and better relaxation. Feldenkrais
practitioners have also noted other benefits in their
students, including improvements in awareness,
flexibility, coordination, breathing, digestion, sleep,
mood, mental alertness, energy, and range of motion,
as well as reduced stress and hypertension, and fewer
headaches and backaches.
Musicians and athletes can improve their performance in many ways when they learn to use their
bodies more efficiently. Feldenkrais can also help
injured athletes regain lost potential and free them
from pain and restriction of movement.
GALE ENCYCLOPEDIA OF MEDICINE

There are numerous accounts of the remarkable
results obtained when Feldenkrais is taught to handicapped children so that they can learn to function
despite their limitations. Handicapped people can
learn to make full use of whatever potential they
have, and to have more confidence in their abilities.
Practitioners who specialize in teaching Feldenkrais to
those who have handicaps have in many cases allowed
the patient to discover ways of performing tasks which
were previously thought to be impossible for them.
The elderly, whose movements are often restricted
by pain and stiffness, can learn to overcome these
obstacles with Feldenkrais instruction. In some
instances even severe cases of arthritis have been conquered. Theoretically, Feldenkrais can make possible
renewed levels of energy and freedom from restriction.

Description
Origins
Moshe Feldenkrais (1904–1984) was a Russianborn Israeli physicist and engineer who was also an
active soccer player and judo master. He devised his
system in response to his own recurring knee injury,
which had restricted his movement and caused him
great pain over a long period of time. Feldenkrais
believed that repeated muscle patterns cause the
parts of the brain controlling those muscles to stay in
a fixed pattern as well. He thought that the more the
muscles are used, the more parts of the brain can be
activated. He devised a method of re-educating the
neuromuscular system and re-evaluating movement
to increase efficiency and reduce stress, using his
knowledge of mechanics and engineering, and applying some of his martial arts training.
Feldenkrais is described a being a dual system, with
two components: ‘‘Awareness Through Movement’’
and ‘‘Functional Integration.’’ The system aims to
re-educate the body so that habitual movements that
cause strain or pain can be relearned to improve
efficiency and eliminate dangerous or painful action.
Feldenkrais helps to translate intention into
action. In practice, an individual can learn to achieve
his or her highest potential, while at the same time
learning to avoid and eliminate stresses, strains, and
the possibility of injury.
Functional integration
During this session, the patient wears comfortable
clothing, and may sit, stand, walk, or lie on a low
padded table. The practitioner helps the pupil by guiding him or her through a number of movements. The
1451

Feldenkrais method

M O S H E F E L D E N K R A I S (1904–1984)

Female genital mutilation

practitioner may use touch to communicate with the
student, but touch is not used to correct any movements.
The purpose of this session is to increase a student’s
awareness of his or her own movement and become
open to different possibilities for movement. The
instruction can be focused on a particular activity that
the student does every day, or that causes him or her
pain. The student can learn to alter habitual movements
and re-educate the neuromuscular system. This type of
session is particularly useful for those who suffer from
limitations originating from misuse, stress, illness, or
accident. It can also help athletes and musicians perform
to the best of their ability by increasing their possibilities
for movement. It offers students the potential for
improving their physical and mental performance in
addition to heightening the sense of well-being.

KEY TERMS
Neuromuscular—The body system of nerves and
muscles as they function together.
Repetitive strain injury—Injury resulting from a
repeated movement such as typing or throwing a ball.

Research and general acceptance
Since Moshe Feldenkrais began to teach his
method, it has gradually gained acceptance as an
education system. Published research using the method
can be found in United States and foreign publications.
Resources

Awareness through movement
Feldenkrais’s martial arts background can be
clearly identified in many of the aspects of Awareness
Through Movement (ATM). During group sessions,
pupils are taught to become acutely aware of all their
movements and to imagine them, so that they can
improve the efficiency of their actions in their minds,
and put them into practice. Pupils are encouraged to be
disciplined about practicing their exercises, to achieve
maximum benefit.
Awareness through movement is described as an
exploratory, nonjudgmental process through which
pupils are encouraged to observe and learn about
themselves and their movements. The range of this
therapy is wide, and there are thousands of different
lessons designed to help specific areas.

Preparations
No preparation is necessary for the practice of
Feldenkrais, and all are encouraged to seek help
from this system. No condition is considered a preclusion to the benefits of Feldenkrais.

Precautions
As with any therapy or treatment, care should be
taken to choose a qualified practitioner. Feldenkrais
practitioners stress that the body must not be forced to
do anything, and if any movement is painful, or even
uncomfortable, it should be discontinued immediately
and the patient should seek professional help.

Side effects
No known side effects are associated with the
practice of Feldenkrais.
1452

BOOKS

Bratman, Steven. The Alternative Medicine Sourcebook. 2nd
ed. Chicago: Lowell House, 1999.
Somerville, Robert. Alternative Medicine: The Definitive
Guide. Tiburon, CA: Future Medicine Publishing, Inc.,
1999.
ORGANIZATIONS

Feldenkrais Guild of North America. 3611 SW Hood Ave.,
Suite 100, Portland, OR 97201. (800) 775-2118. (503)
221-6612. Fax: (503) 221-6616.
<http://www.feldenkrais.com>.

Patricia Skinner

Female circumcision see Female genital
mutilation
Female condom see Condom

Female genital mutilation
Definition
Female genital mutilation (FGM) is the cutting,
or partial or total removal, of the external female
genitalia for cultural, religious, or other non-medical
reasons. It is usually performed on girls between the
ages of four and 10. It is also called female
circumcision.

Purpose
FGM results in the cutting or removal of the
tissues around the vagina that give women pleasurable
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Circumcision—A procedure, usually with religious
or cultural significance, where the prepuce or skin
covering the tip of the penis on a boy, or the clitoris
on a girl, is cut away.
Clitoridectomy—A procedure where the clitoris
and possibly some of the surrounding labial tissue
at the opening of the vagina is cut away.
Infibulation—A procedure where the tissue around
the vagina is sewn shut, leaving only a small opening for the passage of urine and menstrual blood.

Precautions
It is illegal to perform FGM in many countries,
including the United States, Canada, France, Great
Britain, Sweden, Switzerland, Egypt, Kenya, and
Senegal. This procedure is usually done in the home
or somewhere other than a medical setting. Often, it is
performed by a family member or by a local ‘‘circumciser,’’ using knives, razor blades, or other tools that
may not be sterilized before use.

Description
Female circumcision includes a wide range of
procedures. The simplest form involves a small cut to
the clitoris or labial tissue. A Sunna circumcision
removes the prepuce (a fold of skin that covers the
clitoris) and/or the tip of the clitoris. A clitoridectomy
removes the entire clitoris and some or all of the
surrounding tissue; this procedure occurs in approximately 80% of cases. The most extreme form of genital
mutilation is excision and infibulation, in which the
clitoris and all of the surround tissue are cut away and
the remaining skin is sewn together. Only a small
opening is left for the passage of urine and menstrual
blood. Infibulation accounts for approximately 15%
of FGM procedures.
The World Health Organization (WHO) estimates that between 100 million and 140 million girls
and women have undergone some form of FGM. As a
very deeply rooted cultural and religious tradition still
practiced in over 28 African and Asian countries, up to
two million girls per year are at risk. The following
countries have the highest number of occurrences of
FGM: Djibouti (98%), Egypt (97%), Eritrea (95%),
Guinea (99%), Mali (94%), Sierra Leone (90%), and
Somalia (98-100%). As more people move to Western
countries from countries where female circumcision is
performed, the practice has come to the attention of
health professionals in the United States, Canada,
Europe, and Australia.
GALE ENCYCLOPEDIA OF MEDICINE

In an effort to integrate old customs with modern
medical care, some immigrant families have
requested that physicians perform the procedure.
While trying to be sensitive to cultural traditions,
health care providers are sometimes put in the
difficult position of choosing to perform this procedure in a medical facility under sanitary conditions,
or refusing the request, knowing that it may be done
anyway with no medical supervision. Some families
who are intent on having this procedure done will
take their daughters back to the country they immigrated from in order to have the girls circumcised.
Many national and international medical organizations including the American Medical Association
(AMA), Canadian medical organizations, and WHO
oppose the practice of female genital mutilation. The
United Nations (UN) considers female genital mutilation a violation of human rights. WHO has undertaken a number of projects aimed at decreasing the
incidence of FGM. These include the following
activities:


publishing a statement addressing the regional status
of FGM and encouraging the development of
national policy against its practice,



organizing training for regional community workers,



developing educational materials for local health
care workers,



providing alternative occupations for individuals
who perform FGM procedures.

Aftercare
A girl or young woman who has recently had the
procedure performed may require supportive care to
control bleeding and antibiotics to prevent infection.
Women who were circumcised as children may require
1453

Female genital mutilation

sexual feelings. This procedure is used for social and
cultural control of women’s sexuality. In its most
extreme form, infibulation, where the girl’s vagina is
sewn shut, the procedure ensures virginity. In some
cultures where female circumcision has been a
tradition for hundreds of years, this procedure is
considered a rite of passage for young girls. Families
fear that if their daughters are left uncircumcised, they
may not be marriageable. As in most cultures, there
is also the fear that the girl might bring shame to
the family by being sexually active and becoming
pregnant before marriage.

Female sexual arousal disorder

medical care to treat complications. Pregnant women
who have been infibulated may have to have the labial
tissue cut open to allow the baby to be delivered.
Aftercare should be provided with a supportive and
nonjudgmental approach towards the girls and
women who have undergone this procedure.

get turned on,’’ or being continually disinterested in
sex. It is also called ‘‘frigidity.’’ Other terms for the
disorder include dyspareunia and vaginismus, both of
which involve pain during intercourse.

Causes and symptoms
There are numerous causes of this disorder. They
include:

Risks
The immediate risks after the procedure are
hemorrhage (excessive bleeding), severe pain, and
infection (including abscesses, tetanus, and gangrene).
The most severe consequence is death due to excessive
blood loss. Long term complications include scarring,
interference with the drainage of urine and menstrual
blood, chronic urinary tract infections, pelvic and
back pain, and infertility. Sexual intercourse can be
painful. Complications of childbirth are also a risk. It
is unclear whether it is related to the procedure itself,
or related to the general condition of medical practice,
but infant and maternal death rates are generally
higher in those communities where female circumcision is practiced.



physical problems, such as endometriosis, cystitis, or
vaginitis



systemic problems, such as diabetes, high blood
pressure, or hypothyroidism. Even pregnancy or the
postpartum period (time after delivery of a child)
may affect desire. Menopause is also known to reduce
sexual desire.



medications, including oral contraceptives, antidepressants, antihypertensives, and tranquilizers



surgery, such as mastectomy or hysterectomy which
may affect how a woman feels about her sexual self.



stress

Resources



depression

OTHER



use of alcohol, drugs, or cigarette smoking

The Female Genital Mutilation Research Homepage.
<http://www.hollyfeld.org/fgm>.
‘‘Female Genital Mutilation.’’ The World Health Organization.
<http://www.who.int/frh-whd/FGM/index.htm>.

Altha Roberts Edgren

Symptoms vary. A woman may have no desire for
sex, or may not be able to maintain arousal, or may be
unable to reach orgasm. She may also have pain
during sex or orgasm, which interferes with her desire
for intercourse.

Diagnosis

Female infertility see Infertility

Female sexual arousal disorder
Definition
Female sexual arousal disorder (FSAD) occurs
when a woman is continually unable to attain or maintain arousal and lubrication during intercourse, is
unable to reach orgasm, or has no desire for sexual
intercourse.

Description
The disorder typically affects up to 25 percent of
all American women, or an estimated 47 million
women. Three-fourths of women with FSAD are postmenopausal. Women describe it as being ‘‘unable to
1454

To make a diagnosis, a woman’s physician - either
family doctor, gynecologist, or even urologist – takes
a complete medical history to determine when the
problem started, how it presents, how severe it is,
and what the patient thinks may be causing it. The
doctor will also conduct a complete physical examination, looking for any abnormalities in the genital
region

Treatment
The physician should start by providing education
about the disorder and recommending various nonmedical treatment strategies. These include:


use of erotic materials, such as vibrators, books,
magazines and videos



sensual massage, avoiding the genitals



position changes to reduce pain
GALE ENCYCLOPEDIA OF MEDICINE

Dyspareunia— pain in the pelvic area during or
after sexual intercourse.
Vaginismus —An involuntary spasm of the muscles
surrounding the vagina, making penetration painful
or impossible.



use of lubricants to moisten the vagina and genital
area



kegel exercises to strengthen the vagina and clitoris



therapy to overcome any relationship or sexual abuse
issues
Medical treatments include:



estrogen replacement therapy, which may help with
vaginal dryness, pain and arousal



testosterone therapy in women who have low levels
of this male hormone (Side effects, however, may
include deepening voice, hair growth, and acne)



the EROS clitoral therapy device (EROS-CTD),
recently approved by the Food and Drug
Administration; a small vacuum pump, placed over
the clitoris and gently activated to provide a gentle
suction designed to increase blood flow to the region,
which, in turn, helps with arousal



using the herb yohimbine combined with nitric oxide
has been found to increase vaginal blood flow in
postmenopausal women and thus help with some
forms of FSAD

Alternative treatment
Natural estrogens, such as those found in soy
products and flax, may be effective. Herbal remedies
include belladonna, gingko, and motherwort.
However, there is no scientific evidence to prove
these herbs actually help. Some women squirt vitamin
E in their vagina to increase lubrication.

Maintaining a close and open relationship with a
partner is one way to avoid the emotional pain and
isolation that can lead to sexual dysfunction.
Additionally, women should learn if any medications
they take affect sexual function, and should refrain
from alcohol and drugs and quit smoking. Women
who have anxieties and fears about sexual intercourse,
whether because of earlier abuse, rape, or a prudish
upbringing, should deal with those issues through
therapy.
Resources
BOOKS

Berman M. D., Jennifer, Berman Phd, Laura, and Elisabeth
Bumiller. For Women Only: A Revolutionary Guide to
Overcoming Sexual Dysfunction and Reclaiming Your
Sex Life. Henry Holt & Company, Inc., 2001.
Rako, M. D., Susan The Hormone of Desire: The Truth
About Testosterone, Sexuality, and Menopause. Three
Rivers Press, 1999.
Reichman, Judith. I’m Not in the Mood: What EveryWoman
Should Know About Improving Her Libido. Quill
Publishing, 1999.
PERIODICALS

‘‘Consumer Update: Female Sexual Problems.’’ American
Association for Marriage and Family Therapy June 14,
1999.
‘‘Restoring Sexual Health.’’ Consumer Reports On Health.
March 2001: 8-10.
ORGANIZATIONS

Female Sexual Medicine Center UCLA Medical Center. 924
Westwood Blvd., Suite 520 Los Angeles, CA 90024.
(310) 825-0025 <www.newshe.com>.
National Women’s Health Resource Center. 120 Albany
Street Suite 820 New Brunswick, NJ 08901. (877)
986-9472. <www.healthywomen.org>.

Debra Gordon

Femoral hernia see Hernia
Ferritin test see Iron tests

Women may also want to see a sexual therapist for
additional help.

Prognosis
Generally, once women seek the appropriate
help they are quite likely to find a way to resolve
their problems. Often, a holistic approach, using
physical as well as emotional therapies, is required
for success.
GALE ENCYCLOPEDIA OF MEDICINE

Fetal alcohol syndrome
Definition
Fetal alcohol syndrome (FAS) is a pattern of birth
defects, learning, and behavioral problems affecting
individuals whose mothers consumed alcohol during
pregnancy.
1455

Fetal alcohol syndrome

Prevention

KEY TERMS

Fetal alcohol syndrome

Description
FAS is the most common preventable cause of
mental retardation. This condition was first recognized and reported in the medical literature in 1968 in
France and in 1973 in the United States. Alcohol is a
teratogen, the term used for any drug, chemical,
maternal disease or other environmental exposure
that can cause birth defects or functional impairment
in a developing fetus. Some features may be present
at birth including low birth weight, prematurity, and
microcephaly. Characteristic facial features may be
present at birth, or may become more obvious
over time. Signs of brain damage include delays in
development, behavioral abnormalities, and mental
retardation, but affected individuals exhibit a wide
range of abilities and disabilities. It has only been
since 1991 that the long-term outcome of FAS has
been known. Learning, behavioral, and emotional
problems are common in adolescents and adults
with FAS. Fetal Alcohol Effect (FAE), a term no
longer favored, is sometimes used to describe individuals with some, but not all, of the features of
FAS. In 1996, the Institute of Medicine suggested a
five-level system to describe the birth defects, learning and behavioral difficulties in offspring of women
who drank alcohol during pregnancy. This system
contains criteria including confirmation of maternal
alcohol exposure, characteristic facial features,
growth problems, learning and behavioral problems,
and birth defects known to be associated with
prenatal alcohol exposure.
The incidence of FAS varies among different
populations studied, and ranges from approximately
one in 200 to one in 2000 at birth. However, a study
reported in 1997, utilizing the Institute of Medicine
criteria, estimated the prevalence in Seattle,
Washington from 1975–1981 at nearly one in 100 live
births. Avoiding alcohol during pregnancy, including
the earliest weeks of the pregnancy, can prevent FAS.
There is no amount of alcohol use during pregnancy
that has been proven to be completely safe.
There is no racial or ethnic relation to FAS.
Individuals from different genetic backgrounds
exposed to similar amounts of alcohol during pregnancy may exhibit different signs or symptoms of
FAS. Estimates state that 30–45% of women who
consume six or more drinks a day throughout pregnancy will give birth to a child with FAS. The risk of
FAS appears to increase as a chronic alcoholic
woman progresses in her childbearing years and continues to drink. That is, a child with FAS will often be
one of the last born to a chronic alcoholic woman,
although older siblings may exhibit milder features
1456

of FAS. Binge drinking, defined as sporadic use of
five or more standard alcoholic drinks per occasion,
and ‘‘moderate’’ daily drinking (two to four 12 oz
bottles of beer, eight to 16 ounces of wine, two to four
ounces of liquor) can also result in offspring with
features of FAS. Experts say a few binges early in
pregnancy—before a woman may even know she is
pregnant—may be enough to be dangerous, even if
she stops drinking later.

Causes and symptoms
FAS is not a genetic or inherited disorder. It is a
pattern of birth defects, learning, and behavioral problems that are the result of maternal alcohol use during the pregnancy. The alcohol freely crosses the
placenta and causes damage to the developing embryo
or fetus. Alcohol use by the father cannot cause FAS.
If a woman who has FAS drinks alcohol during pregnancy, then she may also have a child with FAS. Not
all individuals from alcohol exposed pregnancies have
obvious signs or symptoms of FAS; individuals of
different genetic backgrounds may be more or less
susceptible to the damage that alcohol can cause.
The dose of alcohol, the time during pregnancy that
alcohol is used, and the pattern of alcohol use all
contribute to the different signs and symptoms that
are found.
Classic features of FAS include short stature, low
birthweight and poor weight gain, microcephaly, and
a characteristic pattern of facial features. These facial
features in infants and children may include small eye
openings (measured from inner corner to outer corner), epicanthal folds (folds of tissue at the inner corner of the eye), small or short nose, low or flat nasal
bridge, smooth or poorly developed philtrum (the area
of the upper lip above the colored part of the lip and
below the nose), thin upper lip, and small chin. Some
of these features are nonspecific, meaning they can
occur in other conditions, or be appropriate for age,
racial, or family background. Other major and minor
birth defects that have been reported include cleft
palate, congenital heart defects, strabismus, hearing
loss, defects of the spine and joints, alteration of the
hand creases, small fingernails, and toenails. Since
FAS was first described in infants and children, the
diagnosis is sometimes more difficult to recognize in
older adolescents and adults. Short stature and microcephaly remain common features, but weight may
normalize, and the individual may actually become
overweight for his/her height. The chin and nose
grow proportionately more than the middle part of
the face and dental crowding may become a problem.
The small eye openings and the appearance of the
GALE ENCYCLOPEDIA OF MEDICINE

Newborns with FAS may have difficulties with
feeding due to a poor suck, have irregular sleep-wake
cycles, decreased or increased muscle tone, seizures or
tremors. Delays in achieving developmental milestones such as rolling over, crawling, walking and
talking may become apparent in infancy. Behavior
and learning difficulties typical in the preschool or
early school years include poor attention span, hyperactivity, poor motor skills, and slow language development. Attention deficit-hyperactivity disorder is a
common associated diagnosis. Learning disabilities or
mental retardation may be diagnosed during this time.
Arithmetic is often the most difficult subject for a child
with FAS. During middle school and high school years
the behavioral difficulties and learning difficulties can
be significant. Memory problems, poor judgment,
difficulties with daily living skills, difficulties with
abstract reasoning skills, and poor social skills are
often apparent by this time. It is important to note
that animal and human studies have shown that
neurologic and behavioral abnormalities can be
present without characteristic facial features. These
individuals may not be identified as having FAS, but
may fulfill criteria for alcohol- related diagnoses, as set
forth by the Institute of Medicine.
In 1991, Streissguth and others reported some of
the first long-term follow-up studies of adolescents
and adults with FAS. In the approximate 60 individuals they studied, the average IQ was 68, with 70
being the lower limit of the normal range. However,
the range of IQ was quite large, as low as 20 (severely
retarded) to as high as 105 (normal). The average
achievement levels for reading, spelling, and arithmetic were fourth grade, third grade and second
grade, respectively. The Vineland Adaptive Behavior
Scale was used to measure adaptive functioning in
these individuals. The composite score for this group
showed functioning at the level of a seven-year-old.
Daily living skills were at a level of nine years, and
social skills were at the level of a six-year-old.
In 1996, Streissguth and others published further
data regarding the disabilities in children, adolescents
and adults with FAS. Secondary disabilities, that is,
those disabilities not present at birth and that might be
preventable with proper diagnosis, treatment, and
intervention, were described. These secondary disabilities include: mental health problems; disrupted school
experiences; trouble with the law; incarceration for
mental health problems, drug abuse, or a crime;
inappropriate sexual behavior; alcohol and drug
GALE ENCYCLOPEDIA OF MEDICINE

abuse; problems with employment; dependent living;
and difficulties parenting their own children. In that
study, only seven out of 90 adults were living and
working independently and successfully. In addition
to the studies by Streissguth, several other authors in
different countries have now reported on long-term
outcome of individuals diagnosed with FAS. In
general, the neurologic, behavioral and emotional
disorders become the most problematic for the individuals. The physical features change over time, sometimes making the correct diagnosis more difficult in
older individuals, without old photographs and other
historical data to review. Mental health problems
including attention deficit, depression, panic attacks,
psychosis and suicide threats and attempts, and overall
were present in more than 90% of the individuals
studied by Streissguth. A 1996 study in Germany
reported more than 70% of the adolescents they
studied had persistent and severe developmental
disabilities and many had psychiatric disorders, the
most common of which were emotional disorders,
repetitive habits, speech disorders, and hyperactivity
disorders.

Diagnosis
FAS is a clinical diagnosis, which means that there
is no blood, x ray or psychological test that can be
performed to confirm the suspected diagnosis. The
diagnosis is made based on the history of maternal
alcohol use, and detailed physical examination for
the characteristic major and minor birth defects
and characteristic facial features. It is often helpful
to examine siblings and parents of an individual
suspected of having FAS, either in person or by
photographs, to determine whether findings on the
examination might be familial, of if other siblings
may also be affected. Sometimes, genetic tests are
performed to rule out other conditions that may
present with developmental delay or birth defects.
Individuals with developmental delay, birth defects
or other unusual features are often referred to a
clinical geneticist, developmental pediatrician, or
neurologist for evaluation and diagnosis of FAS.
Psychoeducational testing to determine IQ and/or
the presence of learning disabilities may also be part
of the evaluation process.

Treatment
There is no treatment for FAS that will reverse
or change the physical features or brain damage
associated with maternal alcohol use during the
pregnancy. Most of the birth defects associated
with prenatal alcohol exposure are correctable with
1457

Fetal alcohol syndrome

upper lip and philtrum may continue to be characteristic. Pubertal changes typically occur at the normal
time.

Fetal alcohol syndrome

KEY TERMS
Cleft palate—A congenital malformation in which
there is an abnormal opening in the roof of the
mouth that allows the nasal passages and the
mouth to be improperly connected.
Congenital—Refers to a disorder that is present at
birth.
IQ—Abbreviation for Intelligence Quotient.
Compares an individual’s mental age to his/her
true or chronological age and multiplies that ratio
by 100.
Microcephaly—An abnormally small head.
Miscarriage—Spontaneous pregnancy loss.
Placenta—The organ responsible for oxygen and
nutrition exchange between a pregnant mother and
her developing baby.
Strabismus—An improper muscle balance of the
ocular musles resulting in crossed or divergent
eyes.
Teratogen—Any drug, chemical, maternal disease,
or exposure that can cause physical or functional
defects in an exposed embryo or fetus.

surgery. Children should have psychoeducational
evaluation to help plan appropriate educational
interventions. Common associated diagnoses such as
attention deficit-hyperactivity disorder, depression, or
anxiety should be recognized and treated appropriately. The disabilities that present during childhood
persist into adult life. However, some of the secondary
disabilities mentioned above may be avoided or
lessened by early and correct diagnosis, better understanding of the life-long complications of FAS, and
intervention. Streissguth has describe a model in
which an individual affected by FAS has one or
more advocates to help provide guidance, structure
and support as the individual seeks to become
independent, successful in school or employment,
and develop satisfying social relationships.

Prognosis
The prognosis for FAS depends on the severity
of birth defects and the brain damage present at
birth. Miscarriage, stillbirth or death in the first
few weeks of life may be outcomes in very severe
cases. Major birth defects associated with FAS are
usually treatable with surgery. Some of the factors
1458

that have been found to reduce the risk of secondary
disabilities in FAS individuals include diagnosis
before the age of six years, stable and nurturing
home environments, never having experienced
personal violence, and referral and eligibility for
disability services. The long-term data helps in
understanding the difficulties that individuals with
FAS encounter throughout their lifetime and can
help families, caregivers and professionals provide
the care, supervision, education and treatment
geared toward their special needs.
Prevention of FAS is the key. Prevention efforts
must include public education efforts aimed at the
entire population, not just women of child bearing
age, appropriate treatment for women with highrisk drinking habits, and increased recognition and
knowledge about FAS by professionals, parents,
and caregivers.
Resources
PERIODICALS

Committee of Substance Abuse and Committee on Children
with Disabilities. ‘‘Fetal Alcohol Syndrome and
Alcohol-Related Neurodevelopmental
Disorders.’’Pediatrics 106 (August 2000): 358-361.
Cramer, C., and F. Davidhizar. ‘‘FAS/FAE: Impact on
Children.’’ Journal of Child Health Care 3 (Autumn
1999): 31-34.
‘‘Fetal Alcohol Syndrome Is Still a Threat, Says
Publication.’’ Science Letter September 28, 2004: 448.
Hannigan, J. H., and D. R. Armant. ‘‘Alcohol in Pregnancy
and Neonatal Outcome.’’ Seminars in Neonatology 5
(August 2000): 243-54.
‘‘Prenatal Exposure to Alcohol.’’ Alcohol Research and
Health 24 (2000): 32-41.
ORGANIZATIONS

Fetal Alcohol Syndrome Family Resource Institute. PO Box
2525, Lynnwood, WA 98036. (253) 531-2878 or (800)
999-3429. <http://www.fetalalcoholsyndrome.org>.
Institute of Medicine. National Academy Press,
Washington, DC. <http://www.come-over.to/FAS/
IOMsummary.htm>.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (888)
663-4637. resourcecenter@modimes.org. <http://
www.modimes.org>.
Nofas. 216 G St. NE, Washington, DC 20002. (202)
785-4585. <http://www.nofas.org>.

Laurie Heron Seaver
Teresa G. Odle

Fetal death see Stillbirth
GALE ENCYCLOPEDIA OF MEDICINE

Definition

Anemia—A disorder characterized by a reduced
blood level of hemoglobin, the oxygen-carrying
pigment of blood.
Hemolytic anemia—A form of anemia caused by
premature destruction of red cells in the blood
stream (a process called hemolysis). Hemolytic
anemias are classified according to whether the
cause of the problem is inside the red blood cell
(in which case it is usually an inherited condition),
or outside the cell (usually acquired later in life).

Fetal hemoglobin (Hemoglobin F), Alkaliresistant hemoglobin, HBF (or Hb F), is the major
hemoglobin component in the bloodstream of the
fetus. After birth, it decreases rapidly until only traces
are found in normal children and adults.

Purpose
The determination of fetal hemoglobin is an aid in
evaluating low concentrations of hemoglobin in the
blood (anemia), as well as the hereditary persistence of
fetal hemoglobin, and a group of inherited disorders
affecting hemoglobin, among which are the thalassemias and sickle cell anemia.

Description
At birth, the newborn’s blood is comprised of
60%–90% of fetal hemoglobin. The fetal hemoglobin
then rapidly decreases to 2% or less after the second to
fourth years. By the time of adulthood, only traces
(0.5% or less) are found in the bloodstream.
In some diseases associated with abnormal
hemoglobin production (see Hemoglobinopathy,
below), fetal hemoglobin may persist in larger
amounts. When this occurs, the elevation raises the
question of possible underlying disease.
For example, HBF can be found in higher levels
in hereditary hemolytic anemias, in all types of leukemias, in pregnancy, diabetes, thyroid disease, and
during anticonvulsant drug therapy. It may also
reappear in adults when the bone marrow is overactive, as in the disorders of pernicious anemia, multiple myeloma, and metastatic cancer in the marrow.
When HBF is increased after age four, it should be
investigated for cause.

to abnormal hemoglobin molecules. In the second
category, normal hemoglobin chains are produced
but in abnormal amounts. An example of the first
category is the disorder of sickle cell anemia, the
inherited condition characterized by curved (sickleshaped) red blood cells and chronic hemolytic anemia.
Disorders in the second category are called the
thalassemias, which are further divided into types
according to which amino acid chain is affected
(alpha or beta), and whether there is one defective
gene (thalassemia minor) or two defective genes
(thalassemia major).

Preparation
This test requires a blood sample. The patient is
not required to be in a fasting state (nothing to eat or
drink for a period of hours before the test).

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting
or feeling lightheaded after venipuncture, or hematoma (blood accumulating under the puncture site).

Hemoglobinopathy
Hemoglobin is the oxygen-carrying pigment found
in red blood cells. It is a large molecule made in the bone
marrow from two components, heme and globin.
Defects in hemoglobin production may be
either genetic or acquired. The genetic defects are
further subdivided into errors of heme production
(porphyria), and those of globin production (known
collectively as the hemoglobinopathies).
There are two categories of hemoglobinopathy.
In the first category, abnormal globin chains give rise
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Reference values vary from laboratory to laboratory but are generally found within the following
ranges:


six months to adult: up to 2% of the total hemoglobin



ewborn to six months: up to 75% of the total
hemoglobin
Abnormal results
Greater than 2% of total hemoglobin is abnormal.
1459

Fetal hemoglobin test

KEY TERMS

Fetal hemoglobin test

Fever

Resources

mechanisms switch on: the blood moves to the
surface and sweating occurs.

BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnosticand
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Fetishes see Sexual perversions

Fever
Definition
A fever is any body temperature elevation over
100 8F (37.8 8C).

Description
A healthy person’s body temperature fluctuates
between 97 8F (36.1 8C) and 100 8F (37.8 8C), with
the average being 98.6 8F (37 8C). The body maintains stability within this range by balancing the heat
produced by the metabolism with the heat lost to the
environment. The ‘‘thermostat’’ that controls this
process is located in the hypothalamus, a small structure located deep within the brain. The nervous system constantly relays information about the body’s
temperature to the thermostat, which in turn activates different physical responses designed to cool
or warm the body, depending on the circumstances.
These responses include: decreasing or increasing the
flow of blood from the body’s core, where it is
warmed, to the surface, where it is cooled; slowing
down or speeding up the rate at which the body turns
food into energy (metabolic rate); inducing shivering,
which generates heat through muscle contraction;
and inducing sweating, which cools the body through
evaporation.
A fever occurs when the thermostat resets at a
higher temperature, primarily in response to an infection. To reach the higher temperature, the body moves
blood to the warmer interior, increases the metabolic
rate, and induces shivering. The ‘‘chills’’ that often
accompany a fever are caused by the movement of
blood to the body’s core, leaving the surface and
extremities cold. Once the higher temperature is
achieved, the shivering and chills stop. When the infection has been overcome or drugs such as aspirin
or acetaminophen (Tylenol) have been taken, the
thermostat resets to normal and the body’s cooling
1460

Fever is an important component of the immune
response, though its role is not completely understood.
Physicians believe that an elevated body temperature
has several effects. The immune system chemicals that
react with the fever-inducing agent and trigger the
resetting of the thermostat also increase the production of cells that fight off the invading bacteria or
viruses. Higher temperatures also inhibit the growth
of some bacteria, while at the same time speeding up
the chemical reactions that help the body’s cells repair
themselves. In addition, the increased heart rate that
may accompany the changes in blood circulation also
speeds the arrival of white blood cells to the sites of
infection.

Causes and symptoms
Fevers are primarily caused by viral or bacterial
infections, such as pneumonia or influenza. However,
other conditions can induce a fever, including allergic reactions; autoimmune diseases; trauma, such as
breaking a bone; cancer; excessive exposure to the
sun; intense exercise; hormonal imbalances; certain
drugs; and damage to the hypothalamus. When an
infection occurs, fever-inducing agents called pyrogens are released, either by the body’s immune
system or by the invading cells themselves, that trigger the resetting of the thermostat. In other circumstances, the immune system may overreact (allergic
reactions) or become damaged (autoimmune diseases), causing the uncontrolled release of pyrogens.
A stroke or tumor can damage the hypothalamus,
causing the body’s thermostat to malfunction.
Excessive exposure to the sun or intensely exercising
in hot weather can result in heat stroke, a condition
in which the body’s cooling mechanisms fail.
Malignant hyperthermia is a rare, inherited condition in which a person develops a very high fever
when given certain anesthetics or muscle relaxants
in preparation for surgery.
How long a fever lasts and how high it may go
depends on several factors, including its cause, the age
of the patient, and his or her overall health. Most
fevers caused by infections are acute, appearing suddenly and then dissipating as the immune system
defeats the infectious agent. An infectious fever may
also rise and fall throughout the day, reaching its peek
in the late afternoon or early evening. A low-grade
fever that lasts for several weeks is associated with
autoimmune diseases such as lupus or with some cancers, particularly leukemia and lymphoma.
GALE ENCYCLOPEDIA OF MEDICINE

Fever

B.
A.

D.
G.
C.

F.

E.

A dramatic rise in body temperature often includes the following symptoms: A. Loss of fluid results in dehydration. B. The
hypothalamic set-point is increased, raising metabolism. C. Blood vessels in skin dilate. D. Sweat glands produce excess
perspiration. E. Increased pulse rate. F. Increased hypothalmic set-point may introduce chills and shivering to promote heat
production from muscles. G. Skin becomes more heat-sensitive. (Illustration by Electronic Illustrators Group.)

Diagnosis
A fever is usually diagnosed using a thermometer. A variety of different thermometers are
available, including traditional glass and mercury
ones used for oral or rectal temperature readings
and more sophisticated electronic ones that can be
inserted in the ear to quickly register the body’s temperature. For adults and older children, temperature
readings are usually taken orally. Younger children
who cannot or will not hold a thermometer in their
mouths can have their temperature taken by placing
an oral thermometer under their armpit. Infants
generally have their temperature taken rectally
using a rectal thermometer.
As important as registering a patient’s temperature
is determining the underlying cause of the fever. The
GALE ENCYCLOPEDIA OF MEDICINE

presence or absence of accompanying symptoms, a
patient’s medical history, and information about what
he or she may have ingested, any recent trips taken, or
possible exposures to illness help the physician make a
diagnosis. Blood tests can aid in identifying an infectious agent by detecting the presence of antibodies
against it or providing samples for growth of the
organism in a culture. Blood tests can also provide the
doctor with white blood cell counts. Ultrasound tests,
magnetic resonance imaging (MRI) tests, or computed
tomography (CT) scans may be ordered if the doctor
cannot readily determine the cause of a fever.

Treatment
Physicians agree that the most effective treatment
for a fever is to address its underlying cause, such as
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Fever evaluation tests

Prognosis

KEY TERMS
Antipyretic—A drug that lowers fever, like aspirin
or acetaminophen.
Autoimmune disease—Condition in which a person’s immune system attacks the body’s own cells,
causing tissue destruction.
Febrile seizure—Convulsions brought on by fever.
Malignant hyperthermia—A rare, inherited condition in which a person develops a very high fever
when given certain anesthetics or muscle relaxants
in preparation for surgery.
Meningitis—A potentially fatal inflammation of the
thin membrane covering the brain and spinal cord.
Metabolism—The chemical process by which the
body turns food into energy, which can be given off
as heat.
Pyrogen—A chemical circulating in the blood that
causes a rise in body temperature.
Reye’s syndrome—A disorder principally affecting
the liver and brain, marked by the rapid development of life-threatening neurological symptoms.

Most fevers caused by infection end as soon as the
immune system rids the body of the pathogen and do
not produce any lasting effects. The prognosis for
fevers associated with more chronic conditions, such
as autoimmune disease, depends upon the overall outcome of the disorder.
Resources
BOOKS

Gelfand, Jeffrey. ‘‘Fever, Including Fever of Unknown
Origin.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al.
New York: McGraw-Hill, 1997.

Bridget Travers

Fever blister see Cold sore

Fever evaluation tests
Definition

through the administration of antibiotics. Also,
because a fever helps the immune system fight infection, it usually should be allowed to run its course.
Drugs to lower fever (antipyretics) can be given if a
patient (particularly a child) is uncomfortable. These
include aspirin, acetaminophen (Tylenol), and ibuprofin (Advil). Aspirin, however, should not be given to a
child or adolescent with a fever since this drug has
been linked to an increased risk of Reye’s syndrome.
Bathing a patient in cool water can also help alleviate a
high fever.

Fever evaluation tests, better known as febrile
agglutinins tests, are performed to detect the presence
of antibodies in the blood that are sensitive to temperature changes. Antibodies are proteins produced by the
immune system in response to specific infectious agents,
such as viruses or bateria. Febrile agglutinins are
antibodies that cause red blood cells to clump, but
only when the blood is warmed to temperatures higher
than the average body temperature of 98.6 8F (37 8C).

A fever requires emergency treatment under the
following circumstances:

The febrile agglutinins test is used to confirm the
diagonsis of certain infectious diseases that stimulate
the body to produce febrile agglutinins. The disease
most commonly diagnosed by this test is brucellosis, a
infection caused by bacteria belonging to the genus
Brucella and characterized by intermittent fever,
sweating, chills, aches, and mental depression. The
test is also used to diagnose certain other infectious
diseases: salmonellosis, caused by Salmonella bacteria
and marked by nausea and severe diarrhea; rickettsial
infections, a group of diseases caused by the bacteria
Rickettsia; and tularemia, also called rabbit fever, a
bacterial infection characterized by a high fever and
swollen lymph nodes. The febrile agglutinins test can
also be used to confirm the presence of two types of



newborn (three months or younger) with a fever over
100.5 8F (38 8C)



infant or child with a fever over 103 8F (39.4 8C)



fever accompanied by severe headache, neck stiffness,
mental confusion, or severe swelling of the throat

A very high fever in a small child can trigger
seizures (febrile seizures) and therefore should be
treated immediately. A fever accompanied by the
above symptoms can indicate the presence of a serious
infection, such as meningitis, and should be brought to
the immediate attention of a physician.
1462

Purpose

GALE ENCYCLOPEDIA OF MEDICINE

Description
A febrile agglutinins test can be performed at a
doctor’s office or a hospital. A nurse or technician will
collect a few drops of blood (about 7ml) in a small tube
that has been cooled slightly. The specimen is then
taken to a laboratory where it heated and examined
for clumping. If the cells clump after warming
and unclump as they cool, a febrile agglutinin titer
(concentration) of greater than 1:80 is present.

Normal results
The results of febrile agglutinins tests require a
doctor’s interpretation. In general, however, a normal
value is lower than 1:32.

Abnormal results
An value higher than 1:80 suggests a diagnosis for
brucellosis or one of the other conditions indicated by
this test.
Jill S. Lasker

Fever of unknown origin
Definition
Fever of unknown origin (FUO) refers to the presence of a documented fever for a specified time, for
which a cause has not been found after a basic medical
evaluation. The classic criteria developed in 1961
included: temperature greater than 101 8F (38.3 8C), for
at least three weeks, and inability to find a cause after one
week of study. Within the past decade, a revision has
been proposed that categorizes FUO into classic, hospital acquired FUO, FUO associated with low white
blood counts, and HIV associated FUO (AIDS related).

Description
Fever is a natural response of the body that helps
in fighting off foreign substances, such as microorganisms, toxins, etc. Body temperature is set by the
thermoregulatory center, located in an area in the
brain called hypothalamus. Body temperature is not
constant all day, but actually is lowest at 6 A.M. and
GALE ENCYCLOPEDIA OF MEDICINE

highest around 4–6 P.M. In addition, temperature
varies in different regions of the body; for example,
rectal and urine temperatures are about one degree
Fahrenheit higher than oral temperature and rectal
temperature is higher than urine. It is also important
to realize that certain normal conditions can effect
body temperature, such as pregnancy, food ingestion,
age, and certain hormonal changes.
Substances that cause fever are known as ‘‘pyrogens.’’ There are two types of pyrogens; exogenous
and endogenous. Those that originate outside the
body, such as bacterial toxins, are called ‘‘exogenous’’
pyrogens. Pyrogens formed by the body’s own cells in
response to an outside stimulus (such as a bacterial
toxin) are called ‘‘endogenous’’ pyrogens.
Researchers have discovered that there are several
‘‘endogenous’’ pyrogens. These are made up of small
groups of amino acids, the building blocks of proteins.
These natural pyrogens have other functions in
addition to inducing fever; they have been named
‘‘cytokines’’. When cytokines are injected into
humans, fever and chills develop within an hour.
Interferon, tumor necrosis factor, and various interleukins are the major fever producing cytokines.
The production of fever is a very complex process;
somehow, these cytokines cause the thermoregulatory
center in the hypothalamus to reset the normal
temperature level. The body’s initial response is to
conserve heat by vasoconstriction, a process in which
blood vessels narrow and prevent heat loss from the
skin and elsewhere. This alone will raise temperature
by two to three degrees. Certain behavioral activities
also occur, such as adding more clothes, seeking
a warmer environment, etc. If the hypothalamus
requires more heat, then shivering occurs.
Fever is a body defense mechanism. It has been
shown that one of the effects of temperature increase is
to slow bacterial growth. However, fever also has
some downsides; the body’s metabolic rate is increased
and with it, oxygen consumption. This can have a
devastating effect on those with poor circulation. In
addition, fever can lead to seizures in the very young.
When temperature elevation occurs for an extended
period of time and no cause is found, the term FUO
is then used. The far majority of these patients are
eventually found to have one of several diseases.

Causes and symptoms
The most frequent cause of FUO is still infection,
though the percentage has decreased in recent years.
Tuberculosis remains an important cause, especially
1463

Fever of unknown origin

cancer, leukemia and lymphoma; however, doctors
rarely use the test for this purpose, since other diagnostic tests are more reliable.

Fever of unknown origin

when it occurs outside the lungs. The decrease in
infections as a cause of FUO is due in part to improved
culture techniques. In addition, technological advances
have made it easier to diagnose non-infectious causes.
For example, tumors and autoimmune diseases in
particular are now easier to diagnose. (An autoimmune
disease is one that arises when the body tolerance
for its own cell antigenic cell markers disappears.)
Allergies to medications can also cause prolonged
fever; sometimes patients will have other symptoms
suggesting an allergic reaction, such as a rash.
There are many possible causes of FUO; generally
though, a diagnosis can be found. About 10% of
patients will wind up without a definite cause, and
about the same percentage have ‘‘factitious fevers’’
(either self induced or no fever at all).
Some general symptoms tend to occur along with
fever; these are called constitutional symptoms and
consist of myalgias (muscle aches), chills, and headache.

Diagnosis
Few symptoms in medicine present such a diagnostic challenge as fever. Nonetheless, if a careful, logical,
and thorough evaluation is performed, a diagnosis will
be found in most cases. The patient’s past medical
history as well as travel, social, and family history
should be carefully searched for important clues.
Usually the first step is to search for an infectious
cause. Skin and other screening tests for diseases such
as tuberculosis, and examination of blood, urine, and
stool, are generally indicated. Antibody levels to a
number of infectious agents can be measured; if these
are rising, they may point to an active infection.
Various x-ray studies are also of value. In addition
to standard examinations, recently developed radiological techniques using ultrasound, computed tomography scan (CT scan) and magnetic resonance
imaging (MRI) scans are now available. These enable
physicians to examine areas that were once accessible
only through surgery. Furthermore, new studies using
radioactive materials (nuclear medicine), can detect
areas of infection and inflammation previously almost
impossible to find, even with surgery.
Biopsies of any suspicious areas found on an x-ray
exam can be performed by either traditional or newer
surgical techniques. Material obtained by biopsy is
then examined by a pathologist to look for clues as to
the cause of the fever. Evidence of infection, tumor or
other diseases can be found in this way. Portions of the
biopsy are also sent to the laboratory for culture in an
attempt to grow and identify an infectious organism.
1464

KEY TERMS
AIDS—Acquired immune deficiency syndrome is
often represented by these initials. The disease is
associated with infection by the human immunodeficiency virus (HIV), and has the main feature of
repeated infections, due to failure of certain parts of
the immune system. Infection by HIV damages part
of the body’s natural immunity, and leads to recurrent illnesses.
Antibiotic—A medication that is designed to kill or
weaken bacteria.
Computed tomography scan (CT Scan)—A specialized x-ray procedure in which cross-sections of the
area in question can be examined in detail. This
allows physicians to examine organs such as the
pancreas, bile ducts, and others which are often the
site of hidden infections.
Magnetic Resonance Imaging (MRI)—This is a new
technique similar to CT Scan, but based on the
magnetic properties of various areas of the body
to compose images.
NSAID—Nonsteroidal anti-inflammatory drugs are
medications such as aspirin and ibuprofen that
decrease pain and inflammation. Many can now
be obtained without a doctor’s prescription.
Ultrasound—A non-invasive procedure based on
changes in sound waves of a frequency that cannot
be heard, but respond to changes in tissue composition. It is very useful for diagnosing diseases of the
gallbladder, liver, and hidden infections, such as
abscesses.

Patients with HIV are an especially difficult
problem, as they often suffer from many unusual
infections. HIV itself is a potential cause of fever.

Treatment
Most patients who undergo evaluation for FUO
do not receive treatment until a clear-cut cause is
found. Antibiotics or medications designed to suppress
a fever (such as NSAIDs) will only hide the true cause.
Once physicians are satisfied that there is no infectious
cause, they may use medications such as NSAIDs, or
corticosteroids to decrease inflammation and diminish
constitutional symptoms.
The development of FUO in certain settings, such
as that acquired by patients in the hospital or in those
with a low white blood count, often needs rapid
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The outlook for patients with FUO depends on
the cause of the fever. If the basic illness is easily
treatable and can be found rather quickly, the potential for a cure is quite good. Some patients continue
with temperature elevations for 6 months or more; if
no serious disease is found, medications such as
NSAIDs are used to decrease the effects of the fever.
Careful follow-up and reevaluation is recommended
in these cases.
Resources
BOOKS

Gelfand, Jeffrey A., and Charles A. Dinarello. ‘‘Fever of
Unknown Origin.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.

David Kaminstein, MD

Fiber-modified diet see Diets
Fibrin degradation products see Fibrin split
products

Fibrin split products
Definition
Fibrin split products (FSP) are fragments of
protein released from a dissolving clot. The fibrin
split products test is one of several tests done to
evaluate a person with blood clotting problems
(coagulation), particularly disseminated intravascular
coagulation (DIC).

Purpose
High levels of FSP in a person’s blood are associated with DIC, a serious medical condition that
develops when the normal balance between bleeding
and clotting is disturbed. Excessive bleeding and
clotting injures body organs, and causes anemia or
death.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Coagulation begins typically with an injury to
some part of the body. The injury sets in motion a
cascade of biochemical activities (the coagulation
cascade) to stop the bleeding, by forming a clot from
a mixture of the blood protein fibrin and platelets.
Once bleeding is stopped, another blood protein
dissolves the clot by breaking down the fibrin into
fragments. Measurement of these fragments gives
information about the clot dissolving portion of
coagulation, called fibrinolysis.
In DIC, the coagulation cascade is triggered in an
abnormal way. A blood infection, a transfusion reaction, a large amount of tissue damage, such as a burn,
a dead fetus, and some cancers can begin the chain of
biochemical events leading to blood clots. The coagulation cascade becomes overwhelmed with excessive
clotting followed by excessive bleeding. As the large
number of clots dissolve, fibrin split products accumulate in the blood and encourage even more bleeding.
Laboratory tests for FSP are done on the yellow
liquid portion left over after blood clots (serum). A
person’s serum is mixed with a substance that binds to
FSP. This bound complex is measured, and the original amount of FSP is determined. Some test methods
give an actual measurement of FSP; some give a titer,
or dilution. Methods that provide a titer look for the
presence or absence of FSP. If the serum is positive for
FSP, the serum is diluted, or titered, and the test is
done again. These steps are repeated until the serum is
so dilute that it no longer gives a positive result. The
last dilution that gives a positive result is the titer
reported.
The FSP test is covered by insurance when
medically necessary. Results are usually available
within one to two hours. Other names for this test
are fibrin degradation products, fibrin breakdown
products, or FDP.

Preparation
This test requires 0.17 oz (5/14m) of blood. A
healthcare worker ties a tourniquet on the patient’s
upper arm, locates a vein in the inner elbow region,
and inserts a needle into that vein. Vacuum action
draws the blood through the needle into an attached
tube. Collection of the sample takes only a few minutes.

Aftercare
Discomfort or bruising may occur at the puncture
site. Pressure applied to the puncture site until the
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Fibrin split products

treatment to avoid serious complications. Therefore,
in these instances patients may be placed on antibiotics
after a minimal number of diagnostic studies. Once
test results are known, treatment can be adjusted as
needed.

Fibrinogen test

PERIODICALS

KEY TERMS
Coagulation—The entire process of blood clotting.
Coagulation cascade—A sequence of biochemical
activities to stop bleeding by forming a clot.

Hardaway, Robert M., and Charles H. Williams.
‘‘Disseminated Intravascular Coagulation: An
Update.’’ Comprehensive Therapy November 1996:
737-743.

Nancy J. Nordenson

Disseminated intravascular coagulation (DIC)—A
serious medical condition that develops when the
normal balance between bleeding and clotting is
disturbed. Excessive bleeding and clotting injures
body organs, and causes anemia or death.
Fibrin split products (FSP)—Pieces of the protein
fibrin released from a dissolving clot.
Fibrinolysis—The clot dissolving portion of the
coagulation process.
Titer—A dilution of a substance with an exact
known amount of fluid. For example, one part of
serum diluted with four parts of saline is a titer of 1:4.

Fibrinogen test
Definition
Fibrinogen (Factor I) is a protein that originates
in the liver. It is converted to fibrin during the bloodclotting process (coagulation).

Purpose
bleeding stops reduces bruising. Warm packs to the
puncture site relieve discomfort. The patient may feel
dizzy or faint.

Risks
People with coagulation problems may bleed
longer than normal. The healthcare provider must
make sure bleeding has stopped before leaving the
patient unattended.

Normal results
Negative at a less than or equal to 1:4 dilution or
less than 10 g/mL.

Abnormal results
High levels of FSP indicate DIC. Results of the
test must be interpreted by the physician according to
the person’s clinical symptoms and medical history.
Other conditions that increase blood clotting activity
also increase FSP: venous thrombosis, surgery and
transplants, blood clots in the lung, certain cancers,
and heart attack (myocardial infarction).
Resources
BOOKS

Miller, Jonathan L. ‘‘Blood Coagulation and Fibrinolysis.’’
In Clinical Diagnosis and Management by Laboratory
Methods, edited by John B.Henry., 19th ed.
Philadelphia: W. B. Saunders Co., 1996.
1466

The fibrinogen test aids in the diagnosis of suspected clotting or bleeding disorders caused by fibrinogen abnormalities.

Precautions
This test is not recommended for patients with
active bleeding, acute infection or illness, or in those
patients who have received blood transfusions within
four weeks.
Drugs that may increase fibrinogen levels include
estrogens and oral contraceptives. Drugs that may
cause decreased levels include anabolic steroids,
androgens, phenobarbital, urokinase, streptokinase,
and valproic acid.

Description
Fibrinogen plays two essential roles in the body: it
is a protein called an acute-phase reactant that
becomes elevated with tissue inflammation or tissue
destruction, and it is also a vital part of the ‘‘common
pathway’’ of the coagulation process.
In order for blood to clot, fibrinogen must be
converted to fibrin by the action of an enzyme
called thrombin. Fibrin molecules clump together to
form long filaments, which trap blood cells to form a
solid clot.
The conversion of fibrinogen to fibrin is the last
step of the ‘‘coagulation cascade,’’ a series of reactions
in the blood triggered by tissue injury and platelet
activation. With each step in the cascade, a
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Fibrin—The last step in the coagulation process.
Fibrin forms strands that add bulk to a forming
blood clot to hold it in place and help ‘‘plug’’ an
injured blood vessel wall.

The factors involved in the coagulation cascade
are numbered I, II, and V through XIII. Factor I is
fibrinogen, while factor II (fibrinogen’s immediate
precursor) is called prothrombin. Most of the coagulation factors are made in the liver, which needs an
adequate supply of vitamin K to manufacture the
different clotting factors.

Platelet—An irregularly shaped cell-like particle in
the blood that is an important part of blood clotting.
Platelets are activated when an injury causes a
blood vessel to break. They change shape from
round to spiny, ‘‘sticking’’ to the broken vessel
wall and to each other to begin the clotting process.

When fibrinogen acts as an ‘‘acute-phase reactant,’’ it rises sharply during tissue inflammation or
injury. When this occurs, high fibrinogen levels may
be a predictor for an increased risk of heart or circulatory disease. Other conditions in which fibrinogen is
elevated are cancers of the stomach, breast, or kidney,
and inflammatory disorders like rheumatoid arthritis.
Reduced fibrinogen levels can be found in liver
disease, prostate cancer, lung disease, bone marrow
lesions, malnourishment, and certain bleeding
disorders. The low levels can be used to evaluate disseminated intravascular coagulation (DIS), a serious
medical condition that develops when there is a disturbed balance between bleeding and clotting. Other
conditions related to decreased fibrinogen levels are
those in which fibrinogen is completely absent (congenital afibrinogenemia), conditions in which levels
are low (hypofibrinogenemia), and conditions of
abnormal fibrinogen (dysfibrinogenemia). Obstetric
complications or trauma may also cause low levels.
Large-volume blood transfusions cause low levels
because banked blood does not contain fibrinogen.

Preparation
This test is performed with a blood sample, which
can be drawn at any time of day. The patient does not
have to be fasting (nothing to eat or drink).

Prothrombin—A type of protein called a glycoprotein that is converted to thrombin during the
clotting process.
Thrombin—An enzyme that converts fibrinogen
into strands of fibrin.

the accumulation of blood under the puncture site
(hematoma).

Normal results
Normal reference ranges are laboratory-specific,
but are usually within the following:


adult: 200 mg/dL–400 mg/dL



newborn: 125 mg/dL–300 mg/dL

Abnormal results
Spontaneous bleeding can occur with values less
than 100 mg/dL.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Aftercare
Because a fibrinogen test is often ordered when a
bleeding disorder is suspected, the patient should
apply pressure or a pressure dressing to the blooddrawn site site for a period of time after blood is
drawn, and then reexamine the site for bleeding.

Fibroadenoma
Definition

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting
or feeling lightheaded after procedure, or the seeing
GALE ENCYCLOPEDIA OF MEDICINE

Fibroadenomas are benign breast tumors commonly found in young women. Fibroadenoma means
‘‘a tumor composed of glandular (related to gland)
and fibrous (containing fibers) tissues.’’
1467

Fibroadenoma

coagulation factor in the blood is converted from an
inactive to an active form. The active form of the
factor then activates several molecules of the next
factor in the series, and so on, until the final step,
when fibrinogen is converted into fibrin.

Fibroadenoma

Description

KEY TERMS

Breast fibroadenomas, abnormal growths of
glandular and fibrous tissues, are most common
between the ages of 15 and 30, and are found in 10%
of all women (20% of African-American women).
They are found rarely in postmenopausal women.

Aspiration —To withdraw material with a needle
and syringe.
Biopsy —To remove cells or tissue for microscopic
examination.

Described as feeling like marbles, these firm,
round, movable, and ‘‘rubbery’’ lumps range from
1–5 cm in size. Giant fibroadenomas are larger,
lemon-sized lumps. Usually single, from 10–15% of
women have more than one.
While some types of breast lumps come and go
during the menstrual cycle, fibroadenomas typically
do not disappear after a woman’s period, and should
be checked by a doctor.

Causes and symptoms
The cause of breast fibroadenomas is unknown.
They may be dependent upon estrogen, because they
are common in premenopausal women, can be found
in postmenopausal women taking estrogen, and
because they grow larger in pregnant women.
Fibroadenomas usually cause no symptoms and
may be discovered during breast self-examination, or
during a routine check-up.

Diagnosis
When the doctor takes a complete medical
history, they will ask when the lump was first noticed,
if there were any symptoms or changes in lump size,
and if there is any personal or family history of breast
disease.
The doctor thoroughly feels the breasts (palpates). Tests are done, usually including mammography or ultrasound scans, or surgical removal of
cells or tissue for examination under a the microscope
(biopsy).
Diagnostic tests include:


Mammogram. An x-ray examination of the breast.



Ultrasound scan. A technique that uses sound waves
to display a two-dimensional image of the breast,
showing whether a lump is solid or fluid-filled (cystic).



Fine-needle aspiration biopsy. A minor procedure
wherein fluid or cells are drawn out of the lump
through a small needle (aspirated).



Core biopsy. A procedure wherein a larger piece of
tissue is withdrawn from the lump through a larger
needle.

1468

Estrogen —Female sex hormone produced by the
ovaries.



Incisional biopsy. A surgical procedure wherein a
piece of the lump is removed through an cut
(incision).



Excisional biopsy. A surgical procedure wherein the
entire lump is removed through an cut (incision).

Most insurance plans cover the costs of diagnosing and treating fibroadenomas.

Treatment
Performed usually in outpatient settings, breast
fibroadenomas are removed by lumpectomy, or surgical excision under local or general anesthesia. Sometimes
lumps in younger women are not removed but are
monitored by self-examination, yearly doctor checkups, and mammograms. Surgery is generally recommended for women over 30, and for lumps that are
painful or enlarging.

Alternative treatment
Alternative treatments for breast fibroadenomas
include a low-fat, high-fiber, vegetarian-type diet; a
reduction in caffeine intake; supplementation with
evening primrose oil (Oenothera biennis), flax oil, or
fish oil and vitamins E and C; and the application of
hot compresses to the breast. In addition, a focus on
liver cleansing is important to assist the body in conjugation and elimination of excess estrogens.
Botanical remedies can be useful in hormone balancing, as can acupuncture and homeopathy. Massaging
the breasts with castor oil, straight or infused with
herbs or essential oils, can help fibroadenomas reduce
and dissipate, as well as keep women in touch with
changes in their breast tissue.

Prognosis
Breast fibroadenomas are not cancerous. The
lumps recur in up to 20% of women. A small number
of lumps disappear on their own.
GALE ENCYCLOPEDIA OF MEDICINE

Breast fibroadenomas cannot be prevented. They
can be discovered early by regular breast selfexamination.

Estimates vary, but 40–90% of all women have
some evidence of ‘‘fibrocystic’’ condition, change, or
disease. It is most common among women between the
ages 30 and 50, but may be seen at other ages.

Causes and symptoms

Resources
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12thStreet, S.W., PO Box 96920.

Mercedes McLaughlin

Fibrocystic breast disease see Fibrocystic
condition of the breast

Fibrocystic condition of the
breast
Definition
Fibrocystic condition of the breast is a term that
may refer to a variety of symptoms: breast lumpiness
or tenderness, microscopic breast tissue, and/or the
x ray or ultrasound picture of the breast. It has been
called a ‘‘wastebasket’’ diagnosis because a wide range
of vaguely defined benign breast conditions may be
labeled as fibrocystic condition. It is not a cancer, and
the majority of types of fibrocystic conditions do not
increase the risk of breast cancer.

Description
There is no such thing as a normal or typical
female breast. Breasts come in all shapes and sizes,
with varying textures from smooth to extremely
lumpy. The tissues of the female breast change in
response to hormone levels, normal aging, nursing
(lactation), weight fluctuations, and injury. To further
complicate matters, the breast has several types of
tissue; each of these tissue types may respond differently to changes in body chemistry.
Fibrocystic breast condition may be called fibrocystic disease, although it is clearly not a single, specific disease process. Variations or changes in the way
the breast feels or looks on x ray may cause the condition to be called ‘‘fibrocystic change.’’ Other names
have been used to refer to this imprecise and ill-defined
term: mammary dysplasia, mastopathy, chronic cystic
mastitis, indurative mastopathy, mastalgia, lumpy
breasts, or physiologic nodularity.
GALE ENCYCLOPEDIA OF MEDICINE

Fibrocystic condition of the breast refers to technical findings on diagnostic testing (signs); however,
this discussion focuses on symptoms that may fall
under the general category of the fibrocystic condition. First, a brief review of the structure and function
of the breast may be useful.
The breast is not supposed to be a soft, smooth
organ. It is actually a type of sweat gland. Milk, the
breasts’ version of sweat, is secreted when the breast
receives appropriate hormonal and environmental
stimulation.
The normal breast contains milk glands, with
their accompanying ducts, or pipelines, for transporting the milk. These complex structures may not only
alter in size, but can increase or decrease in number as
needed. Fibrous connective tissue, fatty tissue, nerves,
blood and lymph vessels, and lymph nodes, with their
different shapes and textures, lie among the ever-changing milk glands. It is no wonder that a woman’s
breasts may not feel uniform in texture and that the
‘‘lumpiness’’ may wax and wane.
The fibrocystic condition refers to the tenderness,
enlargement, and/or changing ‘‘lumpiness’’ that many
women encounter just before or during their menstrual periods. At this time, female hormones are preparing the breasts for pregnancy, by stimulating the
milk-producing cells, and storing fluid. Each breast
may contain as much as three to six teaspoons of
excess fluid. Swelling, with increased sensitivity or
pain, may result. If pregnancy does not occur, the
body reabsorbs the fluid, and the engorgement and
discomfort are relieved.
Symptoms of fibrocystic breast condition range
from mildly annoying in some women to extremely
painful in others. The severity of discomfort may vary
from month to month in the same woman. Although
sometimes distressing, this experience is the body’s
normal response to routine hormonal changes.
This cycle of breast sensitivity, pain and/or enlargement, can also result from medications. Some
hormone replacement therapies (estrogen and progesterone) used for postmenopausal women can produce
these effects. Other medications, primarily, but not
exclusively those with hormones may also provoke
these symptoms.
1469

Fibrocystic condition of the breast

Prevention

Fibrocystic condition of the breast

often the case. Women between the age of 30 and 50
are most likely to develop cysts.

A mammogram of a female breast indicating multiple cysts.
(Custom Medical Stock Photo. Reproduced by permission.)

Breast pain unrelated to hormone shifts is called
‘‘noncyclic’’ pain. ‘‘Trigger-zone breast pain’’ is a term
that may also be used to describe this area-specific
pain. This type of pain may be continuous, or it may
be felt intermittently. Trauma, such as a blow to the
chest area, a prior breast biopsy, or sensitivity to
certain medications may also underlie this type of
pain. Fibrocystic condition of the breast may be cited
as the cause of otherwise unexplained breast pain.
Lumps, apart from those clearly associated with
hormone cycles, may also be placed under the heading
of fibrocystic condition. These lumps stand out from
enlarged general breast tissue. Although noncancerous lumps may occur, the obvious concern with such
lumps is cancer.
Noncancerous breast lumps include:


Adenosis. This condition refers to the enlargement of
breast lobules, which contain a greater number of
glands than usual. If a group of lobules are found
near each other, the affected area may be large
enough to be felt.



Cysts. These are fluid-filled sacs in the breast and
probably develop as ducts that become clogged with
old cells in the process of normal emptying and
filling. Cysts usually feel soft and round or oval.
However a cyst deep within the breast may feel
hard, as it pushes up against firmer breast tissue. A
woman with a cyst may experience pain, especially if
it increases in size before her menstrual cycle, as is

1470



Epithelial hyperplasia. Also called proliferative
breast disease, this condition refers to an overgrowth
of cells lining either the ducts or the lobules.



Fibroadenomas. These are tumors that form in the
tissues outside the milk ducts. The cause of fibroadenomas is unknown. They generally feel smooth and
firm, with a somewhat rubber-like texture. Typically
a fibroadenoma is not attached to surrounding tissue
and moves slightly when touched. They are most
commonly found in adolescents and women in their
early twenties but can occur at any age.



Fibrosis. Sometimes one area of breast tissue persistently feels thicker or more prominent than the rest
of the breast. This feeling may be caused by old
hardened scar tissue and/or dead fat tissue as a result
of surgery or trauma. Often the cause of this type of
breast tissue is unknown.



Miscellaneous disorders. A number of other benign
(noncancerous) breast problems may be placed
under the heading of ‘‘fibrocystic condition.’’ These
problems include disorders that may lead to breast
inflammation (mastitis), infection, and/or nipple
discharge.
Atypical ductal hyperplasia

The condition known as atypical ductal hyperplasia (ADH) is a condition in which the cells lining the
milk ducts of the breast are growing abnormally. This
condition may appear as spots of calcium salts, or
calcifications, on the mammogram. A biopsy removed
from the breast would confirm the diagnosis. Atypical
ductal hyperplasia is not a cancer. In most women, this
condition will cause no problems. However, for some
women, especially women with family histories of
breast cancer, the risk of developing breast cancer is
increased. (One study with over 3,000 female participants indicated that about 20% of the participants
with atypical hyperplasia and a family history of
breast cancer developed breast cancer, as compared
to the 8% of participants who developed the disease
with atypical hyperplasia and no family history of
breast cancer.) For women with ADH and a family
history of breast cancer, more frequent mammograms
and closer monitoring may be required.

Diagnosis
Breast cancer is the most common concern of
women who feel a breast lump or experience an abnormal breast symptom. For peace of mind, and to rule
GALE ENCYCLOPEDIA OF MEDICINE









KEY TERMS
Advanced Breast Biopsy Instrument (ABBI)—Uses
a rotating circular knife and thin heated electrical
wire to remove a large cylinder of abnormal breast
tissue.
Lobules—A small lobe or subdivision of a lobe
(often on a gland) that may be seen on the surface
of the gland by bumps or bulges.
Lymph nodes—Rounded, encapsulated bodies
consisting of an accumulation of lymphatic tissue.

Mammography. A mammogram is an x-ray examination of the breasts. The two major types of
abnormalities doctors look for are masses and calcifications; either abnormality may be benign or malignant. The size, shape, and edges of these masses help
doctors determine whether or not cancer is present.
Sometimes, however, this test may be difficult to
interpret, however, due to dense breast tissue.

Mammotome—A method for removing breast
biopsies using suction to draw tissue into an opening in the side of a cylinder inserted into the breast
tissue. A rotating knife then cuts tissue samples
from the rest of the breast; also known as a
vacuum-assisted biopsy

Ultrasonography. If a suspicious lump is detected
during mammography, an ultrasound (the use of
high-frequency sound waves to outline the shape of
various organs and tissues in the body) is useful
(although not definitive) in distinguishing benign
from cancerous growths.
Ductography. A ductogram (also called a galactogram) is a test that is sometimes useful in evaluating
nipple discharge. A very fine tube is threaded into the
opening of the duct onto the nipple. A small amount
of dye is injected, outlining the shape of the duct on
an x ray, and indicates whether or not there is a mass
in the duct.
Biopsy. If a lump cannot be proven benign by mammography and ultrasound, a breast biopsy may be
considered. Usually a tissue sample is removed
through a needle (fine-needle aspiration biopsy, or
FNAB) to obtain a sample of the lump. The sample is
examined under the microscope by a pathologist,
and a detailed diagnosis regarding the type of benign
lesion or cancer is established. In some cases, however, FNAB may not provide a clear diagnosis, and
another type of biopsy (such as a surgical biopsy,
core-needle biopsy, or other stereotactic biopsy
methods—such as the Mammotome or Advanced
Breast Biopsy Instrument) may be required.

Other breast conditions such as inflammation or
infection are usually recognized on the basis of suspicious history, breastfeeding, or characteristic symptoms
such as pain, redness, and swelling. A positive response
to appropriate therapies often confirms the diagnosis.

Treatment
Once a specific disorder within the broad category
of fibrocystic condition is identified, treatment can be
GALE ENCYCLOPEDIA OF MEDICINE

Stereotactic biopsy—A biopsy taken by precisely
locating areas of abnormal growth through the use
of delicate instruments.

prescribed. There are a number of treatment options
for women with a lump that has been diagnosed
as benign. If it is not causing a great deal of pain, the
growth may be left in the breast. However, some
women may choose to have a lump such as a fibroadenoma surgically removed, especially if it is large.
Another option to relieve the discomfort of a painful
benign lump is to have the cyst suctioned, or drained.
If there is any uncertainty regarding diagnosis, the
fluid may be sent to the lab for analysis.
Symptoms of cycle breast sensitivity and engorgement may also be treated with diet, medication, and/or
physical modifications. For example,


Although there is no scientific data to support this
claim, many women have reported relief of symptoms
when caffeine was reduced or eliminated from their
diets. Decreasing salt before and during the period
when breasts are most sensitive may also ease swelling
and discomfort. Low-fat diets and elimination of
dairy products also appear to decrease soreness for
some women. However, it may take several months
to realize the effects of these various treatments.



Over-the-counter analgesics such as acetaminophen
(Tylenol) or ibuprofen (Advil) may be recommended. In some cases, treatment with prescription
drugs such as hormones or hormone blockers may
prove successful. Oral contraceptives may also be
prescribed.
1471

Fibrocystic condition of the breast

out any possibility of cancer, any newly discovered
breast lumps should be brought to the attention of a
family physician or an obstetrician-gynecologist. He
or she will obtain a history and conduct thorough
physical examination of the area. Depending on the
findings on physical examination, the patient is
usually referred for tests. The most common of these
tests include:

Fibromyalgia







Warm soaks or ice packs may provide comfort.
A well-fitted support bra can minimize physical
movement and do much to relieve breast discomfort.
Breast massage may promote removal of excess fluid
from tissues and alleviate symptoms. Massaging the
breast with castor oil, straight or infused with
herbs or essential oils, can help reduce and dissipate
fibroadenomas as well as keep women in touch with
changes in their breast tissue.
Infections are often treated with warm compresses
and antibiotics. Lactating women are encouraged to
continue breastfeeding because it promotes drainage
and healing. However, a serious infection may
progress to form an abscess that may need surgical
drainage.
Some studies of alternative or complementary treatments, although controversial, have indicated that
vitamins A, B complex and E, and mineral supplements may reduce the risk of developing fibrocystic
condition of the breast. Evening primrose oil
(Oenothera biennis), flaxseed oil, and fish oils have
been reported to be effective in relieving cyclic breast
pain for some women.

Singer, Sydney Ross. Get It Off! Understanding the Cause of
Breast Pain, Cysts, and Cancer. Pahoa, HI: ISCD
Press, 2000.
PERIODICALS

Horner, N.K., and J.W. Lampe. ‘‘Potential Mechanisms of
Diet Therapy for Fibrocystic Breast Conditions Show
Inadequate Evidence of Effectiveness.’’ Journal of the
American Dietetic Association 100 (November 2000):
1368-1380.
Mannello, F., M. Malatesta, and G. Gazzanelli. ‘‘Breast
Cancer in Women With Palpable Breast Cysts.’’ Lancet
354 (August 1999): 677- 678.
Morrow, Monica. ‘‘The Evaluation of Common Breast
Problems.’’ American Family Physician 61 (April 15,
2000): 2371-2378, 2385.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta,
GA 30329. 1-800-ACS-2345. <http://
www.cancer.org>.
American College of Obstetricians and Gynecologists. 409
12th St., S.W., P.O. Box 96920, Washington, DC
20090-6920. <http://www.acog.org>.
Cancer Information Service (CIS). 9000 Rockville Pike,
Building 31, Suite 10A18, Bethesda, MD 20892.
1-800-4-CANCER. <http://wwwicic.nci.nih.gov>.
OTHER

Prognosis
Most benign breast conditions carry no increased
risk for the development of breast cancer. However, a
small percentage of biopsies uncover overgrowth of
tissue in a particular pattern in some women; this
pattern indicates a 15–20% increased risk of breast
cancer over the next 20 years. Strict attention to early
detection measures, such as annual mammograms, is
especially important for these women.

National Cancer Institute. Understanding Breast Changes:
A Health Guide for All Women. July 10, 2001.
<http://rex.nci.nih.gov/MAMMOG_WEB/
PUBS_POSTERS/UNDRSTNDNG/
UNDER_STANDING_CHANGE.html>.

Ellen S. Weber, MSN
Genevieve Slomski, PhD

Fibroids see Uterine fibroids

Prevention
There is no proven method of preventing the various manifestations of fibrocystic condition from
occurring. Some alternative health care practitioners
believe that eliminating foods high in methyl xanthines
(primarily coffee and chocolate) can decrease or
reverse fibrocystic breast changes.
Resources
BOOKS

Goldmann, David R., and David A. Horowitz, editors. The
American College of Physicians Home Medical
Guide: Breast Problems. New York: Dorling
Kindersley, 2000.
Love, Susan M., with Karen Lindsey. Dr. Susan Love’s
Breast Book. 3rd ed., revised. Reading, MA.:
Addison-Wesley, 2000.
1472

Fibromyalgia
Definition
Fibromyalgia is described as inflammation of the
fibrous or connective tissue of the body. Widespread
muscle pain, fatigue, and multiple tender points characterize these conditions. Fibrositis, fibromyalgia, and
fibromyositis are names given to a set of symptoms
believed to be caused by the same general problem.

Description
Fibromyalgia is more common than previously
thought, with as many as 3–6% of the population
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The exact cause of fibromyalgia is not known.
Sometimes it occurs in several members of a family,
suggesting that it may be an inherited disorder. People
with fibromyalgia are most likely to complain of three
primary symptoms: muscle and joint pain, stiffness,
and fatigue.
Pain is the major symptom with aches, tenderness,
and stiffness of multiple muscles, joints, and soft
tissues. The pain also tends to move from one part of
the body to another. It is most common in the neck,
shoulders, chest, arms, legs, hips, and back. Although
the pain is present most of the time and may last for
years, the severity of the pain changes and is dependent on individual patient perception.
Symptoms of fatigue may result from the individual’s chronic pain coupled with anxiety about the
problem and how to find relief. The inflammatory
process also produces chemicals that are known to
cause fatigue. Other common symptoms are tension
headaches, difficulty swallowing, recurrent abdominal
pain, diarrhea, and numbness or tingling of the extremities. Stress, anxiety, depression, or lack of sleep can
increase symptoms. Intensity of symptoms is variable
ranging from gradual improvement to episodes of
recurrent symptoms.

Diagnosis
Diagnosis is difficult and frequently missed
because symptoms of fibromyalgia are vague and generalized. Coexisting nerve and muscle disorders such
as rheumatoid arthritis, spinal arthritis, or Lyme
disease may further complicate the diagnostic process.
Presently, there are no tests available to specifically
diagnose fibromyalgia. The diagnosis is usually made
after ruling out other medical conditions with similar
symptoms and using criteria physicians and researchers have defined.
Because of the emotional distress experienced by
people with this condition and the influence of stress on
the symptoms themselves, fibromyalgia has often been
labeled a psychological problem. Recognition of the
underlying inflammatory process involved in fibromyalgia has helped promote the validity of this disease.
In 1990, the America College of Rheumatology
developed standards for fibromyalgia that health care
practitioners can use to diagnose this condition.
GALE ENCYCLOPEDIA OF MEDICINE

According to these standards, a person is thought to
have fibromyalgia if he or she has widespread pain in
combination with tenderness in at least 11 of the 18
sites known as trigger points. Trigger point sites
include the base of the neck, along the backbone, in
front of the hip and elbow, and at the rear of the knee
and shoulder.

Treatment
There is no known cure for fibromyalgia.
Therefore, the goal of treatment is successful symptom management. Treatment usually requires a
combination of therapies, exercise, proper rest, and
diet. A patient’s clear understanding of his or her role
in the recovery process is imperative for successful
management of this condition. In 2004, a study
demonstrated that a drug called paroxeteine HCI
(Paxil CR) in controlled release tablet form significantly reduced symptoms in fibromyalgia patients.
As of spring 2004, there were no FDA-approved
treatments for fibromyalgia.
Treatments found to be helpful include heat and
occasionally cold applications. A regular stretching
program is often useful. Aerobic activities focusing
on increasing the heart rate are the preferred forms
of exercise over most other forms of exertion. Exercise
programs need to include good warm-up and cooldown sessions, with special attention given to avoiding
exercises causing joint pain. The diet should include a
large variety of fruits and vegetables which provide the
body with trace elements and minerals that are necessary for healthy muscles.
Adequate rest is essential in the treatment of fibromyalgia. Avoidance of stimulating foods or drinks
(such as coffee) and medications like decongestants
prior to bedtime is advised. If diet, exercise, and adequate rest do not relieve the symptoms of fibromyalgia, medications may be prescribed. Medications
prescribed and found to have some benefit include
antidepressant drugs, muscle relaxants, and antiinflammatory drugs.
People with fibromyalgia often need a rheumatology consultation (a meeting with a doctor who
specializes in disorders of the joints, muscles, and
soft tissue) to decide the cause of various rheumatic
symptoms, to be educated about fibromyalgia and
its treatment, and to exclude other rheumatic diseases. A treatment program must be individualized
to meet the patient’s needs. The rheumatologist, as
the team leader, enlists and coordinates the expertise
of other health professionals in the care of the
patient.
1473

Fibromyalgia

affected by the disorder. Fibromyalgia is more prevalent
in adults than children, with more women affected
than men, particularly women of childbearing age.

Fifth disease

ORGANIZATIONS

KEY TERMS
Connective tissue—Tissue that supports and binds
other body tissue and parts.
Lyme disease—An acute recurrent inflammatory
disease involving one or a few joints, believed to
be transmitted by a tickborne virus. The condition
was originally described in the community of
Lyme, Connecticut, but has also been reported in
other parts of the United States and other countries.
Knees, other large joints are most commonly
involved with local inflammation and swelling.
Rheumatology—The study of disorders characterized by inflammation, degeneration of connective
tissue, and related structures of the body. These
disorders are sometimes collectively referred to as
rheumatism.

The American College of Rheumatology. 1800 Century
Place, Suite 250, Atlanta, GA 30345. (404) 633-3777.
<http://www.rheumatology.org>.
Arthritis Foundation.1300 W. Peachtree St., Atlanta, GA
30309. (800) 283-7800. <http://www.arthritis.org>.

Jeffrey P. Larson, RPT
Teresa G. Odle

Fibromyomas see Uterine fibroids
Fibrous breast lumps see Fibroadenoma

Fifth disease
Definition

Alternative treatment
Massage therapy can be helpful, especially when a
family member is instructed on specific massage techniques to manage episodes of increased symptoms.
Specific attention to mental health, including psychological consultation, may also be important, since
depression may precede or accompany fibromyalgia.
Other alternative therapies, including hellerwork,
rolfing, homeopathic medicine, Chinese traditional
medicine (both acupuncture and herbs), polarity
therapy, and Western botanical medicine, can assist
the person with fibromyalgia to function day to day
and can contribute to healing.

Prognosis
Fibromyalgia is a chronic problem. The symptoms sometimes improve and at other times worsen,
but they often continue for months to years.

Prevention
There is no known or specific way to prevent
fibromyalgia. However, similar to many other medical
conditions, remaining as healthy as possible with a
good diet, safe exercise, and adequate rest is the best
prevention.
Resources
PERIODICALS

‘‘Study: Paroxetine Seems to Reduce Fibromyalgia
Symptoms.’’ Obesity, Fitness & Wellness Week June 5,
2004: 803.
1474

Fifth disease is a mild childhood illness caused by
the human parvovirus B19 that causes flu-like
symptoms and a rash. It is called fifth disease because
it was fifth on a list of common childhood illnesses that
are accompanied by a rash, including measles, rubella
or German measles, scarlet fever (or scarlatina), and
scarlatinella, a variant of scarlet fever.

Description
The Latin name for the disease is erythema infectiosum, meaning infectious redness. It is also called the
‘‘slapped cheek disease’’ because, when the bright red
rash first appears on the cheeks, it looks as if the face
has been slapped. Anyone can get the disease, but it
occurs more frequently in school-aged children. The
disease is usually mild, and both children and adults
usually recover quickly without complications. In fact,
some individuals exhibit no symptoms and never even
feel ill. Outbreaks most often occur in the winter and
spring.

Causes and symptoms
Fifth disease is caused by the human parvovirus
B19, a member of the Parvoviridae family of viruses,
that lives in the nose and throat of the infected person.
The virus is spread through the air by coughing and
sneezing. Because the virus needs a rapidly dividing
cell in order to multiply, it attacks the red blood cells
of the body. Once infected, a person is believed to be
immune to reinfection.
Symptoms may appear four to 21 days after being
exposed to the virus. Initial symptoms are flu-like and
GALE ENCYCLOPEDIA OF MEDICINE

Adults generally do not develop a rash, but
instead may have swollen and painful joints, especially
in the hands and feet. In adults, symptoms such as sore
throat, headache, muscle and joint pain, abdominal
pain, diarrhea, and vomiting occur more frequently
than in children and are usually more severe. The
joint pain can be arthritis-like and last for several
months, especially in women, but the disease does
not appear to progress to rheumatoid arthritis.
The virus causes the destruction of red blood
cells and, therefore, a deficiency in the oxygencarrying capacity of the blood (anemia) can result.
In healthy people, the anemia is mild and only lasts a
short while. In people with weakened immune
systems, however, either because they have a chronic
disease like AIDS or cancer (immunocompromised),
or are receiving medication to suppress the immune
system (immunosuppressed), such as organ transplant recipients, this anemia can be severe and last
long after the infection has subsided. Symptoms of
anemia include fatigue, lack of color, lack of energy,
and shortness of breath. Some individuals with sickle
cell anemia, iron deficiency, a number of different
hereditary blood disorders, and those who have
received bone marrow transplantations may be susceptible to developing a potentially life-threatening
complication called a transient aplastic crisis
where the body is temporarily unable to form new
red blood cells.
In very rare instances, the virus can cause inflammation of different areas of the body, including the
brain (encephalitis), the covering of the brain and
spinal cord (meningitis), the lungs (pneumonitis), the
liver (hepatitis), and the heart muscle (myocarditis).
The virus can also aggravate symptoms for people
with an autoimmune disease called systemic lupus
erythematosus.
GALE ENCYCLOPEDIA OF MEDICINE

Fifth disease

include headache, body ache, sore throat, a mild fever
of 101 8F (38.3 8C), and chills. It is at this time, prior
to the development of the rash, that individuals are
contagious. These symptoms last for two to three
days. In children, a bright red rash that looks like a
slap mark develops suddenly on the cheeks. The rash
may be flat or raised and may or may not be itchy.
Sometimes, the rash spreads to the arms, legs, and
trunk, where it has a lace-like or net-like appearance.
The rash can also involve the palms of the hands and
soles of the feet. By the time the rash appears, individuals are no longer infectious. On average, the rash
lasts for 10–11 days, but may last for as long as five to
six weeks. The rash may fade away and then reappear
upon exposure to sunlight, hot baths, emotional distress, or vigorous exercise.

This infant has a rash caused by Fifth disease, or erythema
infectiosum. (Custom Medical Stock Photo. Reproduced by
permission.)

There is some concern about fifth disease in
pregnant women. Although no association with an
increased number of birth defects has been demonstrated, there is concern that infection during the first
three months of pregnancy may lead to a slight increase
in the number of miscarriages. There is also some
concern that infection later in pregnancy may involve
a very small risk of premature delivery or stillbirths. As
a result, women who get fifth disease while they are
pregnant should be monitored closely by a physician.

Diagnosis
Fifth disease is usually suspected based on a
patient’s symptoms, including the typical appearance
of the bright red rash on the cheeks, patient history,
age, and the time of year. The physician will also
exclude other potential causes for the symptoms and
rash, including rubella, infectious mononucleosis,
bacterial infections like Lyme disease, allergic reactions, and lupus.
In addition, there is a blood test for fifth disease,
but it is generally used only for pregnant women and
for people who have weakened immune systems or
who suffer from blood disorders, such as sickle cell
anemia. The test involves measuring for a particular
antibody or protein that the body produces in
response to infection with the human parvovirus
B19. The test is 92–97% specific for this disease.
1475

Filariasis

Prognosis

KEY TERMS
Anemia—A congenital or acquired deficiency in
the iron-carrying capacity of the blood.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Immunocompromised—A state in which the
immune system is weakened or is not functioning
properly due to chronic disease.
Immunosuppressed—A state in which the immune
system is suppressed by medications during the
treatment of other disorders, like cancer, or following an organ transplantation.
Reye’s syndrome—A very serious, rare disease,
most common in children, that involves an upper
respiratory tract infection followed by brain and
liver damage.
Sickle cell anemia—A hereditary blood disorder in
which the red blood cells are misshapen into
crescent or sickle shapes resulting in the reduced
oxygen-carrying capacity of the lungs.

Generally, fifth disease is mild, and patients tend
to improve without any complications. In cases where
the patient is either immunocompromised or immunosuppressed, a life-threatening aplastic crisis can occur.
With prompt treatment, however, the prognosis is
good. Mothers who develop the infection while
pregnant can pass the infection on to their fetus, and
as such, stand an increased risk of miscarriage and
stillbirth. There are tests and treatments, however,
that can be performed on the fetus while still in the
uterus that can reduce the risk of anemia or other
complications.

Prevention
Currently, there is no vaccine against fifth disease.
Avoiding contact with persons who exhibit symptoms
of a cold and maintaining good personal hygiene by
regularly washing hands may minimize the chances of
an infection. Pregnant women should avoid exposure
to persons infected with the disease and notify their
obstetrician immediately if they are exposed so that
they can be tested and monitored closely.
Resources

Because fifth disease can pose problems for an
unborn fetus exposed to the disease through the
mother, testing may also be conducted while a fetus
is still in the uterus. This test uses fluid collected from
the sac around the fetus (amniotic fluid) instead of
blood to detect the viral DNA.

BOOKS

B erktow, Robert, et al., editors. Merck Manual of Diagnosis
and Therapy. Rahway, NJ: Merck Research
Laboratories, 2004.

Lata Cherath, PhD

Treatment
In general, no specific treatment for fifth disease is
required. The symptoms can be treated using over-the
counter medications, such as acetaminophen (Tylenol)
or ibuprofen (Motrin, Advil). If the rash itches, calamine lotion can be applied. Aspirin is usually not given
to children under the age of 18 to prevent the development of a serious illness called Reye’s syndrome.
Patients who are receiving medications to suppress the immune system in the treatment of some
other condition may be allowed to temporarily
decrease the medications in order to allow the immune
system to combat the infection and recover from the
anemia. Those with weakened (not suppressed)
immune systems, such as AIDS patients, may be
given immunoglobulin intravenously to help the
immune system fight the infection. People with severe
anemia or who experience an aplastic crisis may
require hospitalization and blood transfusions.
1476

Filariasis
Definition
Filiariasis is the name for a group of tropical
diseases caused by various thread-like parasitic round
worms (nematodes) and their larvae. The larvae transmit the disease to humans through a mosquito bite.
Filariasis is characterized by fever, chills, headache,
and skin lesions in the early stages and, if untreated,
can progress to include gross enlargement of the limbs
and genitalia in a condition called elephantiasis.

Description
Approximately 170 million people in the tropical
and subtropical areas of southeast Asia, South
GALE ENCYCLOPEDIA OF MEDICINE

In all cases, a mosquito first bites an infected
individual then bites another uninfected individual,
transferring some of the worm larvae to the new host.
Once within the body, the larvae migrate to a particular part of the body and mature to adult worms.
Filariasis is classified into three distinct types according to the part of the body that becomes infected:
lymphatic filariasis affects the circulatory system
that moves tissue fluid and immune cells (lymphatic
system); subcutaneous filariasis infects the areas
beneath the skin and whites of the eye; and serous
cavity filariasis infects body cavities but does not
cause disease. Several different types of worms can
be responsible for each type of filariasis, but the most
common species include the following: Wucheria
bancrofti, Brugia malayi (lymphatic filariasis),
Onchocerca volvulus, Loa loa, Mansonella streptocerca, Dracunculus medinensis (subcutaneous filariasis), Mansonella pustans, and Mansonella ozzardi
(serous cavity filariasis).
The two most common types of the disease are
Bancroftian and Malayan filariasis, both forms of
lymphatic filariasis. The Bancroftian variety is found
throughout Africa, southern and southeastern Asia,
the Pacific islands, and the tropical and subtropical
regions of South America and the Caribbean.
Malayan filariasis occurs only in southern and southeastern Asia. Filariasis is occasionally found in the
United States, especially among immigrants from the
Caribbean and Pacific islands.
A larvae matures into an adult worm within six
months to one year and can live between four and
six years. Each female worm can produce millions
of larvae, and these larvae only appear in the
bloodstream at night, when they may be transmitted, via an insect bite, to another host. A single
bite is usually not enough to acquire an infection,
therefore, short-term travelers are usually safe. A
series of multiple bites over a period of time is
required to establish an infection. As a result, those
individuals who are regularly active outdoors at
night and those who spend more time in remote
jungle areas are at an increased risk of contracting
the filariasis infection.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
In cases of lymphatic filariasis, the most common
form of the disease, the disease is caused by the adult
worms actually living in the lymphatic vessels near the
lymph nodes where they distort the vessels and cause
local inflammation. In advanced stages, the worms
can actually obstruct the vessels, causing the surrounding tissue to become enlarged. In Bancroftian
filariasis, the legs and genitals are most often involved,
while the Malayan variety affects the legs below the
knees. Repeated episodes of inflammation lead to
blockages of the lymphatic system, especially in the
genitals and legs. This causes the affected area to
become grossly enlarged, with thickened, coarse skin,
leading to a condition called elephantiasis.
In conjunctiva filariasis, the worms’ larvae
migrate to the eye and can sometimes be seen moving
beneath the skin or beneath the white part of the eye
(conjunctiva). If untreated, this disease can cause a
type of blindness known as onchocerciasis.
Symptoms vary, depending on what type of parasitic worm has caused the infection, but all infections
usually begin with chills, headache, and fever between
three months and one year after the insect bite. There
may also be swelling, redness, and pain in the arms,
legs, or scrotum. Areas of pus (abscesses) may appear
as a result of dying worms or a secondary bacterial
infection.

Diagnosis
The disease is diagnosed by taking a patient
history, performing a physical examination, and by
screening blood specimens for specific proteins
produced by the immune system in response to this
infection (antibodies). Early diagnosis may be difficult
because, in the first stages, the disease mimics other
bacterial skin infections. To make an accurate
diagnosis, the physician looks for a pattern of inflammation and signs of lymphatic obstruction, together
with the patient’s possible exposure to filariasis in an
area where filariasis is common. The larvae (microfilariae) can also be found in the blood, but because
mosquitos, which spread the disease, are active at
night, the larvae are usually only found in the blood
between about 10 pm and 2 am.

Treatment
Either ivermectin, albendazole, or diethylcarbamazine is used to treat a filariasis infection by eliminating the larvae, impairing the adult worms’ ability
to reproduce, and by actually killing adult worms.
1477

Filariasis

America, Africa, and the islands of the Pacific
are affected by this debilitating parasitic disease.
While filariasis is rarely fatal, it is the second leading cause of permanent and long-term disability
in the world. The World Health Organization
(WHO) has named filariasis one of only six ‘‘potentially eradicable’’ infectious diseases and has
embarked upon a 20-year campaign to eradicate the
disease.

Filariasis

Unfortunately, much of the tissue damage may not be
reversible. The medication is started at low doses to
prevent reactions caused by large numbers of dying
parasites.

KEY TERMS
Abscess—An area of inflamed and injured body
tissue that fills with pus.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.

While effective, the medications can cause severe
side effects in up to 70% of patients as a result either of
the drug itself or the massive death of parasites in the
blood. Diethylcarbamazine, for example, can cause
severe allergic reactions and the formation of pusfilled sores (abscesses). These side effects can be controlled using antihistamines and anti-inflammatory
drugs (corticosteroids). Rarely, treatment with diethylcarbamazine in someone with very high levels of parasite infection may lead to a fatal inflammation of the
brain (encephalitis). In this case, the fever is followed
by headache and confusion, then stupor and coma
caused when massive numbers of larvae and parasites
die. Other common drug reactions include dizziness,
weakness, and nausea.

Conjunctiva—The mucous membrane that lines
the inside of the eyelid and the exposed surface of
the eyeball.
Elephantiasis—A condition characterized by the
gross enlargement of limbs and/or the genitalia
that is also accompanied by a hardening and
stretching of the overlying skin. Often a result of
an obstruction in the lymphatic system caused by
infection with a filarial worm.
Encephalitis—Inflammation of the brain.
Lymphatic system—The circulatory system that
drains and circulates fluid containing nutrients,
waste products, and immune cells, from between
cells, organs, and other tissue spaces.

Symptoms caused by the death of the parasites
include fever, headache, muscle pain, abdominal pain,
nausea and vomiting, weakness, dizziness, lethargy,
and asthma. Reactions usually begin within two days
of starting treatment and may last between two and
four days.
No treatment can reverse elephantiasis. Surgery
may be used to remove surplus tissue and provide a
way to drain the fluid around the damaged lymphatic
vessels. Surgery may also be used to ease massive
enlargement of the scrotum. Elephantiasis of the legs
can also be helped by elevating the legs and providing
support with elastic bandages.

Microfilariae—The larvae and infective form of
filarial worms.
Nematode—Round worms.
Subcutaneous—The area directly beneath the skin.



treat one or two sets of clothing ahead of time with
permethrin (Duramon, Permanone).



wear DEET insect repellent or, especially for children, try citronella or lemon eucalyptus, to repel
insects



if sleeping in an open area or in a room with poor
screens, use a bed net to avoid being bitten while
asleep



use air conditioning, the cooler air makes insects less
active.

Prognosis
The outlook is good in early or mild cases, especially if the patient can avoid being infected again. The
disease is rarely fatal, and with continued WHO medical intervention, even gross elephantiasis is now
becoming rare.

Prevention
The best method of preventing filariasis is to prevent being repeatedly bitten by the mosquitoes that
carry the disease. Some methods of preventing insect
bites include the following:


limit outdoor activities at night, particularly in rural
or jungle areas



wear long sleeves and pants and avoid dark-colored
clothing that attracts mosquitoes



avoid perfumes and colognes

1478

In addition, filariasis can be controlled in highly
infested areas by taking ivermectin preventatively
before being bitten. Currently, there is no vaccine
available, but scientists are working on a preventative
vaccine at this time.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

GALE ENCYCLOPEDIA OF MEDICINE

‘‘Bacterial Diseases.’’ ‘‘Health touch Online Page.’’ <http://
www.healthtouch.com>.
Centers for Disease Control.<http://www.cdc.gov/nccdphp/
ddt/ddthome.htm>.
International Society of Travel Medicine.
<http:www.istm.org>.
King, J. W. Bug Bytes.Louisiana State University Medical
Center.<http://www.ccm.lsumc.edu/bugbytes>.
‘‘Lymphatic Filariasis.’’ Centers for Disease Control.
<http://www.cdc.gov/travel/yellowbk/page117.htm>.

Carol A. Turkington

prostate gradually shrinks, the patient finds it easier
to pass urine without discomfort and to empty the
bladder completely before going to sleep. Some
doctors also prescribe finasteride as pretreatment for
prostate surgery, as it lowers the risk of severe bleeding
during the operation.
As of early 2005, the National Cancer Institute
(NCI) was evaluating finasteride as a possible chemo
preventative for prostate cancer in selected patients.
Researchers were not yet certain, however, which men
might benefit most from taking the drug.

Description

Filgras see Cancer therapy, supportive;
Immunologic therapies

Finasteride

Finasteride inhibits the body’s production of an
enzyme called 5-alpha-reductase, which is needed
to convert testosterone to another androgen called
5-alpha-dihydrotestosterone (DHT). Finasteride is a
white powder that can be dissolved in alcohol or
chloroform but is very difficult to dissolve in water.
Both Proscar and Propecia are manufactured as
coated tablets to be taken by mouth.

Definition
Finasteride is a drug that belongs to the class of
androgen inhibitors, which means that it blocks the
production of male sex hormones. It is sold in the
United States and Canada under the brand names
Proscar and Propecia.

Purpose
Finasteride has two main purposes: the treatment
of urinary problems in men caused by benign prostatic
hypertrophy (BPH) or enlargement of the prostate
gland; and the stimulation of new hair growth in men
with male pattern baldness. Finasteride was first
approved by the Food and Drug Administration
(FDA) in 1992 under the trade name Proscar as a
treatment for BPH. It received a second FDA approval
in December 1997 under the trade name Propecia
for the treatment of hair loss in men. Finasteride has
also been used by some European doctors to treat hair
loss in postmenopausal women, although its use in
women is considered controversial in the United
States. It is considered the most effective nonsurgical
treatment for male pattern baldness as of 2005.
Finasteride works to relieve such symptoms of
prostate enlargement as urinary urgency, the need to
urinate frequently at night (nocturia), inability to
completely empty the bladder, incontinence, or painful urination (dysuria) by blocking the production of
DHT. DHT causes the prostate gland to grow and
increase pressure on the bladder. As the swollen
GALE ENCYCLOPEDIA OF MEDICINE

Recommended dosage


Proscar: Finasteride for treatment of an enlarged
prostate is taken once a day as a 5-mg tablet. The
pill may be crushed or broken if the patient finds it
hard to swallow.



Propecia: Finasteride for hair regrowth is taken once
a day as a 1-mg tablet. The drug may be taken with or
without meals, as the patient prefers.

Precautions
Finasteride should be stored in dry places and
should be kept at a temperature between 598F and
868F (15–308C). Heat and moisture may cause the
drug to lose its potency.
The drug can be safely handled by pregnant
women as long as the tablets are intact; however,
crushed or broken tablets should not be touched by a
pregnant woman as the drug can be absorbed through
the skin. If the woman is carrying a male fetus, the
drug can cause abnormalities in the baby’s sex organs.
The FDA issued a warning in 2003 that men taking
finasteride should not donate blood until one month
after the final dose of the drug, on the grounds that
their blood could contain high enough levels of the
medication to cause birth defects in a male baby if
given to a pregnant woman.
Patients should be advised that finasteride takes
several months to reach its full effect—as long as six
1479

Finasteride

OTHER

Finasteride

Interactions

KEY TERMS
Alopecia—The medical term for baldness.
Androgens—A group of hormones that produces
masculine characteristics.
Chemo preventative—Description of a drug given
in order to prevent the development of a specific
disease. Finasteride was in 2005 being evaluated as
a possible cancer chemo preventative.
Dysuria—Painful or difficult urination.
Incontinence—Inability to control urination or
defecation.
Nocturia—Excessive need to urinate at night.
Prostate—A gland in males below the bladder that
surrounds the urethra. Enlargement of the prostate
may cause problems in urination.
Urgency—A sudden and powerful need to urinate.

months for BPH and three months for hair regrowth.
In addition, the drug’s effects on the body are not
permanent; the prostate will start to enlarge again or
the hair growth will be lost if the patient stops taking
the drug.
Proscar can affect the results of a prostate-specific
antigen (PSA) test for cancer of the prostate. Between
30 and 50 percent of men taking the drug will have
elevated levels of PSA in their blood serum.
Finasteride should be used cautiously by men with
liver disorders.

Side effects
As of 2005 reported side effects from using finasteride include:

As of 2005 finasteride has not been reported to
cause significant interactions with other medications.
Resources
BOOKS

‘‘Alopecia (Baldness).’’ Section 10, Chapter 116 in The
Merck Manual of Diagnosis and Therapy, edited by
Mark H. Beers, and Robert Berkow. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
‘‘Benign Prostatic Hyperplasia (Benign Prostatic
Hypertrophy).’’ Section 17, Chapter 218 in The Merck
Manual of Diagnosis and Therapy, edited by Mark H.
Beers and Robert Berkow. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
Wilson, Billie A., et al. Nurses Drug Guide 2000, Stamford,
CT: Appleton & Lange, 2000.
PERIODICALS

Arca, E., G. Acikgoz, H. B. Tastan, et al. ‘‘An Open,
Randomized, Comparative Study of Oral Finasteride
and 5% Topical Minoxidil in Male Androgenetic
Alopecia.’’ Dermatology 209 (2004): 117–125.
Crea, G., G. Sanfilippo, G. Anastasi, et al. ‘‘Pre-Surgical
Finasteride Therapy in Patients Treated Endoscopically
for Benign Prostatic Hyperplasia.’’ Urologia
Internationalis 74 (January 2005): 51–53.
Haber, R. S. ‘‘Pharmacologic Management of Pattern Hair
Loss.’’ Facial Plastic Surgery Clinics of North America
12 (May 2004): 181–89.
Parnes, H. L., I. M. Thompson, and L. G. Ford. ‘‘Prevention
of Hormone-Related Cancers: Prostate Cancer.’’
Journal of Clinical Oncology 23 (January 10, 2005):
368–77.
Trueb, R. M., and the Swiss Trichology Group. ‘‘Finasteride
Treatment of Patterned Hair Loss in Normoandrogenic
Postmenopausal Women.’’ Dermatology 209 (2004):
202–07.
ORGANIZATIONS

American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814.
(301)657-3000. <www.ashp.org>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888)
INFO-FDA. <www.fda.gov>.



impotence or loss of interest in sex



lumps or pain in the breast or a discharge from the
nipple



skin rash, itching, or hives



swelling of the lips or face

OTHER



a smaller quantity of ejaculate during intercourse
(which does not affect fertility)



headaches, dizziness, or diarrhea

Food and Drug Administration (FDA) Medication Deferral
List, December 9, 2003. <http://www.fda.gov/ohrms/
dockets/ac/03/briefing/4014b1_18_Medicationlist%20.doc>.



pain in the testicles

These side effects are more common with the 5-mg
dose, but usually go away as soon as the drug is
discontinued.
1480

Rebecca J. Frey, PhD

Fingernail removal see Nail removal
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Fingertip trauma covers cuts, accumulation of
blood (hematoma), bone breakage, or amputation in
the fingertip.

Description
The fingertips are specialized areas of the hand
with highly developed sensory and manipulative functions. Large sensory and motor areas located in the
brain regulate the precise and delicate functions of
fingertips. The fingertip is the site where extensor
and flexor tendons insert. Fingertip injuries are extremely common since the hands hold a wide array of
objects. In 2001, the approximately 10% of all accidents in the United States referred for Emergency
Room consults involve the hand. Hand injuries are
frequently the result of job injuries and account for
11–14% of on-the-job injuries and 6% of compensation paid injuries. Injury to the nail bed occurs in
approximately 15–24% of fingertip injuries.
Fingertip injuries can result in amputation or
tissue loss. The injury is assessed whether the bone
and underlying tissue are intact and the size of the
wound area. The pulp is the area of skin opposite the
fingernail and is usually very vulnerable to injury.
Pulp injuries commonly occur in persons who use or
are in close contact with fast moving mechanical
devices. These injuries can crush, cut, and puncture.
The fingertips can also be injured by common crushing accidents. This could cause the development of a
subungal hematoma (an accumulation of blood
under the nail). At the base of the distal phalanx
(the first circular skin fold from the tip) injuries can
occur that can fracture the underlying bone in the
area. Quite commonly a hammer, closing a door, or
sport accidents usually cause these injuries. These
fractures can be simple, requiring little treatment or
more complicated involving the joint. The accident
may involve the point of insertion of a tendon.
Usually this occurs when the terminal joint is being
forced to flex while held straight. This motion
typically occurs when tucking in sheets during bed
making, a common cause of tendon injury. This
injury causes a loss of extension (straightening the
finger) ability.

Causes and symptoms
Accidental amputations will usually result in
profuse bleeding and tissue loss. Injuries to the pulp
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
The attending clinician should evaluate the
injury in a careful and systematic manner. The
appearance of the hand can provide valuable information concerning presence of fractures, vascular
status, and tendon involvement. Bones and joints
should be evaluated for motion and tenderness.
Nerves should be examined for sensory (feeling
sensations) and motor (movement) functioning.
Amputations usually profusely bleed and there is
tissue loss. The wound is treated based on loss of
tissue, bone, and wound area. Injuries to the pulp
can be obvious during inspection. Subungal hematoma usually present a purplish-black discoloration
under the nail. This is due to a hematoma underneath
the nail. Radiographs may be required to assess the
alignment of fractures or detect foreign bodies.
Patients usually suffer from pain since injuries to
the fingertip bone are usually painful and movement
may be partially restricted due to swelling of the
affected area. Tendon injuries usually result in the
loss of ability to straighten or bend the finger.

Treatment
Amputation with bone and underlying tissue
intact and a wound area 1 cm or less should be
cleaned and treated with a dressing. With these
types of wounds healthy tissue will usually grow and
replace the injured area. Larger wounds may require
surgical intervention. Puncture wounds should be
cleaned and left open to heal. Patients typically
receive antibiotics to prevent infection. A procedure
called trephining treats subungal hematomas. This
procedure is usually done with a straight cutting
needle positioned over the nail. The clinician spins
the needle with forefinger and thumb until a hole is
made through the nail.
1481

Fingertip injuries

Fingertip injuries

can occur as from fast moving mechanical instruments, such as drills. These injuries may puncture the
pulp. Injuries such as a subungal hematoma are
caused by a crushing type injury. Fractures typically
occur as the result of crushing injuries or tendon
avulsion. These crushing injuries are frequently caused
during sport injury and can be treated by simple interventions such as immobilization or more complex
procedures if tendons are affected (the trauma is then
treated as a tendon injury). Fractures can cause pain
and, depending on the extent of swelling, there may be
some restriction of movement. Tendon injuries can
be caused when the terminal joint is exposed to force
flexing motion (moving the finger toward the palm)
while held straight.

Fish and shellfish poisoning

KEY TERMS
Distal—Movement away from the origin.
Flex—To bend.
Laceration—A cut in the skin
Phalanx—A bone of the fingers or toes.
Tendon—A structure that connects a skeletal
muscle to bone.

Fish and shellfish poisoning
Definition
Fish and shellfish poisoning is a common but often
unrecognized group of illnesses related to food. Three
of these illnesses include ciguatera, scombroid, and
paralytic shellfish poisoning.

Ciguatera
Definition

Patients who have extensive crush injuries or
subungal hematomas involving laceration to skin
folds or nail damage should have the nail removed to
examine the underlying tissue (called the matrix).
Patients who have a closed subungal hematoma with
an intact nail and no other damage (no nail disruption
or laceration) are treated conservatively. If the fracture is located two-thirds below the fingertip immobilization using a splint may be needed. Conservative
treatment is recommended for crush injuries that
fracture the terminal phalanx if a subungal hematoma
is not present. Severe fractures near the fist circular
skin crease may require surgical correction to prevent
irregularity of the joint surface, which can cause
difficulty with movement. Injury to a flexor tendon
usually requires surgical repair. If this is not possible,
the finger and wrist should be placed in a splint
with specific positioning to prevent further damage.

Prognosis
Prognosis depends on the extent of traumatic
damage to the affected area. Nail lacerations that are
not treated may cause nail deformities. When amputation is accompanied with loss of two-thirds of the nail,
half of the fingers develop beaking, or a curved nail.
Aftercare and follow up are important components of
treatment. The patient is advised to keep the hand
elevated, check with a clinician two days after
treatment, and to splint fractures for two weeks
in the extended position. Usually a nail takes about
100 days to fully grow. Healing for an amputation
takes about 21 to 27 days. This markedly decreases
in elderly patients, primarily due to a compromised
circulation normally part of advancing age.
Resources
BOOKS

Townshend, Courtney M., et al. Sabiston Textbook of
Surgery. 16th ed. W. B. Saunders Company, 2001.

Laith Farid Gulli, M.D.
1482

Ciguatera (from the Spanish word for a poisonous
snail) is a food-related illness that causes abdominal
and neurological symptoms.
Causes and symptoms
Ciguatera is caused by eating fish that have a toxin
called ciguatoxin. Scientists believe this toxin is
acquired by the fish through the food chain, and is
originally produced by small algae microorganisms
(dinoflagellates). The fish most likely contaminated
with ciguatoxin are those that feed close to tropical
reefs, including red snapper, grouper, and barracuda.
Larger fish are more likely to contain the toxin.
Although not as common in the United States, ciguatera is commonly diagnosed on many of the islands in
the Pacific Ocean.
Illness from ciguatera can occur in just a few
minutes to about 30 hours after eating. Most cases
occur one to six hours after eating the contaminated
fish. Initial symptoms are abdominal cramps, nausea,
vomiting, or watery diarrhea. The most characteristic
symptoms of the illness are those involving the nervous system. These include numbness and tingling
around the lips, tongue, and mouth; itching; dry
mouth; metallic taste in the mouth; and blurry vision.
In more prominent cases, patients may complain of
temporary blindness, a slow pulse, and a feeling that
their teeth are loose. Patients may also have the
strange symptom of reversal of hot and cold sensations on the skin, where cold things feel very hot or
painful to the touch. In very severe cases, there may be
difficulties in breathing or low blood pressure.
Diagnosis
Ciguatera diagnosis is based on the typical combination of symptoms after eating fish. There are no
readily available blood or urine tests to detect the
poisoning, but some researchers have developed a
test for the toxin left on any remaining fish. A person
does not have to be in a tropical area to get ciguatera.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
The treatment for this illness is general. Patients
are given fluids (by mouth or through a vein) and
medications to decrease the itching or to treat vomiting and/or diarrhea. The neurological symptoms can
cause discomfort and treatment with amitriptyline (a
medicine that has been used for depression) may be
useful. Other medications may also be given.
Prognosis
Although death can occur, almost all patients
diagnosed with ciguatera will recover. Recovery, however, can be slow and some symptoms can last for
weeks or even months. Symptoms can also be aggravated by other illnesses or alcohol.
Prevention
Knowing the kinds of fish linked to ciguatera can
help a person avoid eating high-risk fish. However,
over 400 different kinds of fish have been linked to the
disease, even salmon. A particular fish in a given area
may be more likely to cause ciguatera than other fish.
For example, red snapper is most often the source of
ciguatera in the Pacific, while barracuda is more likely
to contain the toxin in Florida. This is why it is illegal
to sell barracuda in Florida for human consumption.
Cooking the fish does not prevent ciguatera.

Scombroid
Definition
Scombroid is a fish-associated illness caused by
eating improperly handled fish. Fish linked to this
disease are usually in the Scombridae family, which
includes yellowfin tuna, skipjack, bonito, and
mackerel.

produces histamine and other chemicals that cause
the illness when the fish is eaten.
Symptoms of scombroid occur quickly after eating the fish, as soon as 10 minutes. Since histamine is
released by certain cells in the body during an allergic
reaction, scombroid can be confused with a fish
allergy. Scombroid causes flushing of the face, sweating, a burning feeling in the mouth or throat, vomiting, diarrhea, and headaches. A rash that looks like a
sunburn may occur, and a small number of patients
have hives. Some patients have a metallic or peppery
taste in their mouths. In more severe cases, rapid pulse,
blurred vision, and difficulty breathing can occur.
Symptoms usually last about four hours.
Diagnosis
Like ciguatera, scombroid poisoning is diagnosed
based on typical symptoms occurring after eating fish.
There are usually no available tests for the patient.
Experimentally, however, elevated levels of histaminerelated products have been found in the urine. It
may be possible for public health officials to test any
remaining fish flesh for histamine levels. Improperly
refrigerated fish caught in both temperate and tropical
waters have been linked to the illness. An outbreak of
similar cases may be helpful in correctly diagnosing the
problem.
Treatment
The treatment for scombroid is usually general.
Antihistamines like diphenhydramine (Benadryl) may
shorten the duration of the illness, but the illness will
go away on its own. Some doctors have found that
cimetidine (Tagamet) given through a vein may be
helpful as well. In rare, more severe cases, epinephrine
(adrenaline) may be used.
Prognosis
Although sometimes dramatic and alarming
symptoms can occur, scombroid is usually not serious.
The patient should be reassured that scombroid is not
a fish allergy.

Causes and symptoms
Scombroid occurs after eating fish that has
not been properly refrigerated after capture. Unlike
ciguatera, the toxins linked with scombroid are not
contracted by the fish from its surroundings. Bacteria
that are normally found in fish act directly on a
chemical (called histidine) in the flesh of fish that are
not properly cooled when stored. This interaction
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Adequate storage of the target fish will always
prevent scombroid. Since the fish does not appear
spoiled or smell bad, the consumer cannot detect the
risk of the illness before eating the fish. Cooking the
fish does not prevent scombroid. Suspected cases
should be reported to public health officials.
1483

Fish and shellfish poisoning

Fish can be caught from one of these distant areas, and
can then be shipped and eaten locally. It is important
to report suspected cases to local public health officials
because more cases may occur from other contaminated fish.

Fistula

Paralytic shellfish poisoning

KEY TERMS

Definition
Paralytic shellfish poisoning (PSP) is a nervous
system disease caused by eating cooked or raw shellfish that contain environmental toxins. These toxins
are produced by a group of algae (dinoflagellates). It is
unclear whether these toxins are related to the
‘‘blooming’’ of the algae, also called red tide because
the algae can turn the water reddish brown. PSP
occurs mostly in May through November.

Algae—Plants that have one cell.
Histamine—A chemical found naturally in the
body that produces inflammation and increases
blood flow; the uncomfortable symptoms of an
allergy attack or an allergic reaction are generally
caused by the release of histamine.
Toxin—A poisonous substance usually produced
by a living thing.

Causes and symptoms
PSP develops usually within minutes after eating a
contaminated shellfish, most commonly a mussel,
clam, or oyster. Symptoms include headache, a floating feeling, dizziness, lack of coordination, and
tingling of the mouth, arms, or legs. Muscle weakness
causing difficulty swallowing or speaking may occur.
Abdominal symptoms such as nausea, vomiting, and
diarrhea can also occur. Unlike ciguatera and
scombroid, PSP may have a much more serious
outcome. PSP may cause difficulty breathing related
to weakness or paralysis of the breathing muscle. The
symptoms may last for six to 12 hours, but a patient
may continue to feel weak for a week or more.
Diagnosis

Prevention
Measures to control PSP require detecting rising
numbers of algae in coastal waters by periodic microscopic examination. By law, shellfish beds are closed
when levels of the toxin-producing organisms are
above acceptable standards. Cooking the shellfish
does not prevent this disease. Suspected cases should
be reported to public health officials.
Resources
PERIODICALS

Barton, Erik D., Paula Tanner, Steven G. Turchen, et al.
‘‘Ciguatera Fish Poisoning: A Southern California
Epidemic.’’ Western Journal of Medicine 163, no. 1 (July
1995): 31–35.

PSP diagnosis is based on symptoms after eating
shellfish, even if the shellfish are adequately cooked.
No blood or urine test is available to diagnose the
illness, but tests in mice to detect the toxin from the
eaten fish can be done by public health officials.

Larry I. Lutwick, MD, FACP

Treatment
The treatment of PSP is mostly supportive. If
early symptoms are recognized, the doctor will try to
flush the toxin from the gastrointestinal tract with
medications that create diarrhea. Vomiting may be
induced if the patient has no signs of weakness. In
cases where the muscles of breathing are weakened,
the patient may be placed on a respirator until the
weakness goes away. However, this measure is not
usually needed. Likewise, the use of a machine to
clean the blood (dialysis) has been used in severe cases.
Prognosis
The prognosis for PSP is quite good, especially if
the patient has passed the initial 12 hours of illness
without needing breathing support. Most deaths occur
during this period if breathing help is not available.
1484

Fistula
Definition
A Fistula is a permanent abnormal passageway
between two organs in the body or between an organ
and the exterior of the body.

Description
Fistulas can arise in any part of the body, but they
are most common in the digestive tract. They can also
develop between blood vessels and in the urinary,
reproductive, and lymphatic systems. Fistulas can
occur at any age or can be present at birth (congenital). Some are life-threatening, others cause discomfort, while still others are benign and go undetected or
cause few symptoms. Diabetics, individuals with
GALE ENCYCLOPEDIA OF MEDICINE

Fistulas are categorized by the number of openings they have and whether they connect two internal
organs or open through the skin. There are four
common types:


Blind fistulas are open on one end only.



Complete fistulas have one internal opening and one
opening on the skin.



Horseshoe fistulas are complex fistulas with more
than one opening on the exterior of the body.



Incomplete fistulas are tubes of skin that are open
on the outside but closed on the inside and do not
connect to any internal structure.
Fistulas of the digestive tract

Anal and rectal fistulas develop in the wall of the
anus or rectum. They connect the interior of the body
to one or several openings in the skin. Anal and rectal
fistulas almost always begin as an inflammation in
an anal gland. The inflammation then moves into
muscle tissue and develops into an abscess. In about
half of all cases, the abscess develops into a fistula,
degrading the muscle until an opening in the skin is
created. About 9 people of every 100,000 develop
anal fistulas, with men almost twice more likely to
develop the condition than women. Although they
may develop at any age, the average age for the
development of anal fistulas is 38.
Intestinal fistulas can develop in both the large
and small intestine. They are commonly associated
with diseases such as inflammatory bowel disease
(IBD) and Crohn’s disease.
Tracheoesophageal fistulas (TEF) are usually
birth defects. The windpipe, or trachea, is abnormally
connected to the esophagus. This allows air to enter
the digestive system and makes it possible to breathe
food into the lungs (aspiration). In many cases, the
esophagus is also incomplete, causing immediate
feeding problems. There are several types of TEFs
categorized by where the fistula is located and how
the esophagus and trachea are connected, but all are
life-threatening and require prompt surgery to repair.
TEFs occur in about one of every 1,500–3,000 births.
Fistulas of the urinary and reproductive tract
The most common type of fistula involving these
systems is a vesicovaginal fistula, in which the
GALE ENCYCLOPEDIA OF MEDICINE

woman’s vagina is connected to the urinary bladder.
This causes leakage of urine from the vagina and
results in frequent vaginal and bladder infections.
Fistulas may also develop between the vagina and
the large intestine (a enterovaginal fistula) so that
feces leaks from the vagina. Although both these
types of fistulas are uncommon in the developed
world, they are common in poor developing
countries and result from long, difficult labor and
childbirth, especially in very young girls. As a
result, they are sometimes referred to as obstetric
fistulas.
Some experts suggest that in parts of Africa, as
many as 3–4 women develop these fistulas out of every
1,000 births. Others estimate that as many as 2 million
women worldwide are living with unrepaired obstetric
fistulas. If left unrepaired, obstetric fistulas cause
women to constantly leak urine and feces. As a result,
they become social outcasts, causing them extreme
hardship and psychological trauma.
Fistulas of the circulatory system
Arteriovenous fistulas (AVF) can develop
between an artery and a vein in any part of the body.
These fistulas vary in size, length, and frequency.
Arteries contain blood carrying oxygen to all parts of
the body, while veins carry blood that has given up its
oxygen back to the lungs. Connections between
arteries and veins cause changes in blood pressure
that result in abnormal development of the walls of
the arteries and abnormal blood flow. Arteriovenous
fistulas that are present at birth are sometimes referred
to as arteriovenous malformations (AVMs). Many
arteriovenous fistulas are present, but not evident at
birth, and become obvious only after trauma. AVFs
can also be acquired from penetrating trauma.

Causes and symptoms
The causes and symptoms of fistulas vary depending on their location. Anal and rectal fistulas are
usually caused by an abscess. Symptoms include constant throbbing pain and swelling in the rectal area.
Pus is sometimes visible draining from the fistula
opening on the skin. Many individuals have a fever
resulting from the infection causing the abscess.
Vaginal fistulas are caused by infection and
trauma to the tissue during childbirth. They are easily
detected, because the woman smells unpleasant and
leaks urine or feces through her vagina. Rarely these
fistulas may develop as a complication of
hysterectomy.
1485

Fistula

compromised immune systems (AIDS, cancer) and
individuals with certain gastrointestinal diseases
(Crohn’s disease, inflammatory bowel disease) are at
increased risk of developing fistulas.

Fistula

Tracheoesophageal fistulas are the result of errors
in the development of the fetus. They are evident at
birth, because the infant is unable to swallow or eat
normally and are considered a medical emergency that
requires surgery if the infant is to survive.
Arteriovenous fistulas are most often congenital
defects. Symptoms vary depending on the size and
location of the fistula. Often the skin is bright pink
or dark red in the area of the fistula. Individuals may
complain of pain. The pain is a result of some tissues
not receiving enough oxygen because of abnormal
blood flow.

Diagnosis
Tests use to determine the presence of a fistula
vary with the location of the fistula. When there is an
opening to the outside, the physician may be able to
see the fistula and probe it. Various imaging studies
such as x rays, CT scans, barium enemas, endoscopy,
and ultrasonography are used to locate less visible
fistulas.

Treatment
Anal and rectal fistulas are treated by draining the
pus the infected area. The individual also is usually
given antibiotics to help prevent recurrence of the
abscess. If this fails to heal the fistula, surgery may
be necessary.
Intestinal fistulas are treated first by reducing the
inflammation in the intestine and then, if necessary
with surgery. Treatment varies considerably depending on the degree of severity of symptoms the fistula
causes. TEFs are always treated with surgery.
Obstetric fistulas must also be repaired with surgery.
The treatment of arteriovenous fistulas depends on the
size and location of the fistula and usually includes
surgery.

Alternative treatment
No effective alternative treatments for fistulas are
known.

Prognosis
The outcome of fistulas depends on the type and
cause of the condition. Surgical repair of obstetric
fistulas is almost always successful. Unfortunately,
many women in developing countries do not have
access to this type of surgery. Treatment of anal and
rectal fistulas is almost always successful, although
fistulas may recur in up to 18% of individuals. The
1486

KEY TERMS
Abscess—A collection of pus surrounded by
inflamed, infected tissue.
Lymphatic system—The part of the circulatory
system that carries lymph, a clear fluid that is
involved in immune system response.

outcome of surgery on TEFs is highly variable,
especially since infants born with this condition
often have other developmental abnormalities that
may affect the outcome of fistula repair. The degree
of successful repair of arteriovenous fistulas depends
on their size and location. Uncontrolled bleeding
is the most common complication of surgery to
repair AVFs.

Prevention
Obstetric fistulas are the only preventable fistulas.
These can be prevented with good prenatal and childbirth care and by avoiding pregnancy in very young
girls. Although anal and rectal fistulas are not preventable, their damage can be minimized by prompt drainage and treatment.
Resources
ORGANIZATIONS

American Society of Colon and Rectal Surgeons. 85
W. Algonquin Road, Suite 550, Arlington Heights, IL
60005. 847-290-9184. <http://www.facrs.org>.
OTHER

Legall, Ingrid. Anal Fistulas and Fissures, 11 June 2004 [cited
16 February 2005]. <http://www.emedicine.com/
emerg/topic495.htm>.
‘‘Fistula.’’ Medline Plus Medical Encyclopedia 29 October
2003 [cited 16 February 2005]. <http://
www.nlm.nih.gov/medlineplus/ency/
article/002365.htm>
Morasch, Mark D. and Dipen Maun. Arteriovenous
Fistulas, 24 October 2003 [cited 16 February 2005].
<http://www.emedicine.com/med/topic169.htm>.
Zagrodnik, Dennis II. Fistula-in-Ano, ii June 2004 [cited 3
March 2005]. <http://www.emedicine.com/med/
topic2710.htm>.

Tish Davidson, A.M.

5p-syndrome see Cri du chat syndrome
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Flesh-eating disease is more properly called necrotizing fasciitis, a rare condition in which bacteria
destroy tissues underlying the skin. This tissue death,
called necrosis or gangrene, spreads rapidly. This
disease can be fatal in as little as 12 to 24 hours.

Description
Although the term is technically incorrect, flesheating disease is an apt descriptor: the infection
appears to devour body tissue. Media reports
increased in the middle and late 1990s, but the disease
is not new. Hippocrates described it more than three
millennia ago and thousands of reports exist from the
Civil War. Approximately 500 to 1,500 cases of necrotizing fasciitis occur in the United States each year.
Flesh-eating disease is divided into two types.
Type I is caused by anaerobic bacteria, with or without
the presence of aerobic bacteria. Type II, also called
hemolytic streptococcal gangrene, is caused by group
A streptococci; other bacteria may or may not be
present. The disease may also be called synergistic
gangrene.
Type I fasciitis typically affects the trunk, abdomen, and genital area. For example, Fournier’s gangrene is a ‘‘flesh-eating’’ disease in which the infection
encompasses the external genitalia. The arms and legs
are most often affected in type II fasciitis, but the
infection may appear anywhere.

Causes and symptoms
The two most important factors in determining
whether or not a person will develop flesh-eating disease are: the virulence (ability to cause disease) of the
bacteria and the susceptibility (ability of a person’s
immune system to respond to infection) of the person
who becomes infected with this bacteria.
In nearly every case of flesh-eating disease, a skin
injury precedes the disease. As bacteria grow beneath
the skin’s surface, they produce toxins. These toxins
destroy superficial fascia, subcutaneous fat, and deep
fascia. In some cases, the overlying dermis and the
underlying muscle are also affected.
Initially, the infected area appears red and swollen
and feels hot. The area is extremely painful, which is a
prominent feature of the disease. Over the course of
hours or days, the skin may become blue-gray, and
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
The appearance of the skin, paired with pain and
fever raises the possibility of flesh-eating disease. An
x ray, magnetic resonance imaging (MRI), or computed tomography scans (CT scans) of the area reveals
a feathery pattern in the tissue, caused by accumulating gas in the dying tissue. Necrosis is evident during
exploratory surgery, during which samples are collected for bacterial identification.

Treatment
Rapid, aggressive medical treatment, specifically,
antibiotic therapy and surgical debridement, is
imperative. Antibiotics may include penicillin, an
aminoglycoside or third-generation cephalosporin,
and clindamycin or metronidazole. Analgesics are
employed for pain control. During surgical debridement, dead tissue is stripped away. After surgery,
patients are rigorously monitored for continued infection, shock, or other complications. If available,
hyperbaric oxygen therapy has also be used.

Prognosis
Flesh-eating disease has a fatality rate of about
30%. Diabetes, arteriosclerosis, immunosuppression,
kidney disease, malnutrition, and obesity are connected
with a poor prognosis. Older individuals and intravenous drug users may also be at higher risk. The infection site also has a role. Survivors may require plastic
surgery and may have to contend with permanent
physical disability and psychological adjustment.

Prevention
Flesh-eating disease, which occurs very rarely,
cannot be definitively prevented. The best ways to
lower the risk of contracting flesh-eating disease are:


take care to avoid any injury to the skin that may give
the bacteria a place of entry



when skin injuries do occur, they should be promptly
washed and treated with an antibiotic ointment or
spray



people who have any skin injury should rigorously
attempt to avoid people who are infected with
1487

Flesh-eating disease

Flesh-eating disease

fluid-filled blisters may form. As nerves are destroyed
the area becomes numb. An individual may go into
shock and develop dangerously low blood pressure.
Multiple organ failure may occur, quickly followed
by death.

Flower remedies

ORGANIZATIONS

KEY TERMS
Aerobic bacteria—Bacteria that require oxygen to
live and grow.
Anaerobic bacteria—Bacteria that require the
absence of oxygen to live and grow.
CT scan (computed tomography scan)—Crosssectional x rays of the body are compiled to create
a three-dimensional image of the body’s internal
structures.
Debridement—Surgical procedure in which dead
or dying tissue is removed.
Dermis—The deepest layer of skin.
Fascia, deep—A fibrous layer of tissue that envelopes muscles.
Fascia, superficial—A fibrous layer of tissue that
lies between the deepest layer of skin and the
subcutaneous fat.
Gangrene—An extensive area of dead tissue.
Hyperbaric oxygen therapy—A treatment in which
the patient is placed in a chamber and breathes
oxygen at higher-than-atmospheric pressure. This
high-pressure oxygen stops bacteria from growing
and, at high enough pressure, kills them.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Necrosis—Abnormal death of cells, potentially
caused by disease or infection.
Subcutaneous—Referring to the area beneath the
skin.

streptococci bacteria, a bacteria that causes a simple
strep throat in one person may cause flesh-eating
disease in another


have any areas of unexplained redness, pain, or swelling examined by a doctor, particularly if the affected
area seems to be expanding

Resources
BOOKS

Roemmele, Jacqueline A., Donna Batdorff, and Alan L.
Bisno. Surviving the ‘Flesh-Eating Bacteria’:
Understanding, Preventing, Treating, and Living
With the Effects of Necrotizing Fascitis. New York:
Avery Penguin Putnam, 2000.
1488

National Necrotizing Fascitis Foundation. PO Box 145,
Niantic, CT 06357. (616) 261-2538. <http://
www.nnff.org/>.

Paul A. Johnson, Ed.M.

Flight medicine see Aviation medicine
Floppy mitral valve see Mitral valve prolapse

Flower remedies
Definition
Flower remedies are specially prepared flower
essences, containing the healing energy of plants.
They are prescribed according to a patient’s emotional
disposition, as ascertained by the therapist, doctor, or
patients themselves.

Purpose
Flower remedies are more homeopathic than herbal in the way they work, effecting energy levels rather
than chemical balances. They have been described as
‘‘liquid energy.’’ The theory is that they encapsulate the
flowers’ healing energy, and are said to deal with and
overcome negative emotions, and so relieve blockages
in the flow of human energy that can cause illness.

Description
Origins
Perhaps the most famous and widely used system
is the Bach flower remedies. This system originated in
the 1920s when British physician and bacteriologist,
Dr. Edward Bach (1886–1936), noticed that patients
with physical complaints often seemed to be suffering
from anxiety or some kind of negative emotion.
He concluded that assessing a patient’s emotional
disposition and prescribing an appropriate flower
essence could treat the physical illness. Bach was a
qualified medical doctor, but he also practiced
homeopathy.
As a result of his own serious illness in 1917,
Bach began a search for a new and simple system of
medicine that would treat the whole person. In 1930,
he gave up his flourishing practice on Harley Street at
the Royal London Homeopathic Hospital and moved
to the countryside to devote his life to this research. It
GALE ENCYCLOPEDIA OF MEDICINE

Edward Bach was a graduate of University College
Hospital (M.B., B.S., M.R.C.S.) in England. He left his
flourishing Harley Street practice in favor of homeopathy, seeking a more natural system of healing than
allopathic medicine. He concluded that healing should
be as simple and natural as the development of plants,
which were nourished and given healing properties by
earth, air, water, and sun.
Bach believed that he could sense the individual
healing properties of flowers by placing his hands over
the petals. His remedies were prepared by floating summer flowers in a bowl of clear stream water exposed to
sunlight for three hours.
He developed 38 remedies, one for each of the
negative states of mind suffered by human beings,
which he classified under seven group headings: fear,
uncertainty, insufficient interest in present circumstances, loneliness, over-sensitivity to influences and
ideas, despondency or despair, and overcare for the
welfare of others. The Bach remedies can be prescribed
for plants, animals, and other living creatures as well as
human beings.

is known that at this point, he ceased to dispense the
mixture of homeopathy and allopathic medicine that
he had been using. Instead, he began investigating the
healing properties of plant essences and discovered
that he possessed an ‘‘intuition’’ for judging the properties of each flower. Accordingly, he developed the
system of treatment that bears his name, and is also the
foundation for all other flower-remedy systems.
The Bach Flower Remedies were ostensibly the
only system of significance from the 1920s until in the
1970s, when there was a renewed interest in the subject
by doctors working in the field of natural medicine.
Perhaps the most notable was Dr. Richard Katz, who
was seeking new methods of dealing with modern
stress and the resulting ailments. He focused on the
concept of a psychic, psychological effect and chose to
pursue this line of research.
In 1979, Katz founded the Flower Essence Society
in California, (FES). This society pledged to further
the research and development of Bach’s principles. As
of 2000, FES hosts a database of over 100 flower
essences from more than 50 countries. FES is now an
international organization of health practitioners,
researchers, students, and others concerned with
flower essence therapy.
GALE ENCYCLOPEDIA OF MEDICINE

Bach Flower Remedies

Name

Remedy

Agrimony

Upset by arguments, nonconfrontational, conceals
worry and pain
Fear of the unknown, anxiety, prone to nightmares, and
apprehension
Critical, intolerant, and negative
Submissive and weak-willed
Self doubting and overly dependent
Emotional thoughts and desparation
Repeats mistakes and has no hindsight
Selfish, controlling, attention-seeking, and possessive
Absorbed, impractical, and indifferent
Shame and self-loathing
Overwelhmed and feelings of inadequacy
Negative, doubt, and depression
Pessimism, hopelessness, and despair
Self-centered and self-absorbed
Jealousy, hatred, suspicion, and envy
Homesick, living in the past, and nostalgic
Procrastination, fatigue, and mental exhaustion
Impatience, irritability, and impulsive
No confidence, inferiority complex, and despondency
Timid, shy, and fear of the unknown
Sadness and depression of unknown origin
Obstinate, inflexible, and overachieving
Exhaustion
Guilt and self blame
Fear and anxiety for loved ones
Nightmares, hysteria, terror, and panic
Obsessive, repression, perfectionism, and self denial
Indecision, low mental clarity, and confusion
Grief and distress

Aspen
Beech
Centaury
Cerato
Cherry Plum
Chestnut
Chicory
Clematis
Crab Apple
Elm
Gentian
Gorse
Heather
Holly
Honeysuckle
Hornbeam
Impatiens
Larch
Mimulus
Mustard
Oak
Olive
Pine
Red Chesnut
Rock Rose
Rock Water
Scleranthus
Star-ofBethlehem
Sweet
Chesnut
Vervain
Vine
Walnut
Water Violet
White
Chestnut
Wild Oat
Wild Rose
Willow

Despair and hopelessness
Overbearing and fanatical
Arrogant, ruthless, and inflexible
Difficulty accepting change
Pride and aloofness
Worry, preoccupation, and unwanted thoughts
Dissatisfaction
Apathy and resignation
Self pity and bitterness

The Society has connections with an estimated
50,000 active practitioners from around the world,
who use flower essence therapy as part of their
treatment. FES encourages the study of the plants
themselves to determine the characteristics of flower
essences. They are compiling an extensive database
of case studies and practitioner reports of the use of
essences therapeutically, allowing verification and
development of the original definitions. They are also
engaged in the scientific study of flower essence
therapy.
FES says they have developed the theories of
Paracelsus and Goethe who researched the ‘‘signatures’’ and ‘‘gestures’’ of botanical specimens, on the
premise that the human body and soul are a reflection
1489

Flower remedies

E D W A R D B A C H (1886–1936)

Flower remedies

of the system of nature. FES plant research interprets
the therapeutic properties of flower essences according
to these insights.
In this regard, they have devised 12 ‘‘windows of
perception’’ for monitoring the attributes of plants.
Each of these windows reveals an aspect of the plant’s
qualities, although they maintain that what they are
seeking is a ‘‘whole which is greater than the sum of its
parts.’’ The 12 windows are not considered independent classifications, but more of a blended tapestry of
views of the qualities that each plant possesses.
The first window is concerned with the ‘‘form’’
of a plant—its shape classification. The second
focuses on its ‘‘gesture’’ or spatial relationship. The
third window is a plant’s botanical classification;
the Flower Essence Society maintains that considering a plant’s botanical family is essential to obtaining
an overview of its properties as a flower essence. The
fourth window concerns the time orientation of a
particular specimen regarding the daily and seasonal
cycles. Why do some flowers bloom at different
times of the day, while others, such as the evening
primrose, respond to the moon? The fifth window
observes a plant’s relationship to its environment.
Where a plant chooses to grow, and where it cannot
survive, reveals much about its qualities. The sixth
window observes a plant’s relationship to the Four
Elements and the Four Ethers, as FES maintains
that plants exist in one of the elemental or etheric
forces in addition to their physical life. ‘‘Elements’’
refers to those developed by the Greeks, as opposed
to the modern concept of ‘‘molecular building
blocks.’’ It seems that commonly, two elements
predominate in a plant, indicating a polarity of
qualities, while two can be said to be recessive. The
seventh window relates to a plant’s relationship with
the other kingdoms of nature: mineral, animal and
human, while the eighth relates to the color and color
variations of a plant. Katz explains how the language
of color tells us so much about the ‘‘soul qualities’’ of
a plant. The ninth window concerns all other sensory
perceptions of a plant, such as fragrance, texture,
and taste. The tenth window involves assessing the
chemical substances and properties; the eleventh
studies medicinal and herbal uses, as by studying
the physical healing properties of plants, we can
also understand something of their more subtle
effects on the soul. Finally, the twelfth window
involves the study of the lore, mythology, folk
wisdom, and spiritual and ritual qualities associated
with a particular plant. Katz relates how in the past,
human beings were more in touch with the natural
world, and the remnants of this unconscious plant
1490

wisdom live on in the form of folklore, mythology,
and so on.
Because flower remedies operate on approximately the same principles as homeopathy, practitioners quite often prescribe the two therapies in
conjunction with each other. They can also be used
concurrently with allopathic medicine.
The system consists of 38 remedies, each for a
different disposition. The basic theory is that if the
remedy for the correct disposition is chosen, the
physical illness resulting from the present emotional
state can then be cured. There is a rescue remedy made
up of five of the essences—cherry plum, clematis,
impatiens, rock star, and star of Bethlehem—that
is recommended for the treatment of any kind of
physical or emotional shock. Therapists recommended that rescue remedy be kept on hand to help
with all emergencies.
The 38 Bach Remedies


agrimony: puts on a cheerful front, hides true feelings, and worries or problems



aspen: feelings of apprehension, dark foreboding,
and premonitions



beech: critical, intolerant, picky



centaury: easily comes under the influence of others,
weak willed



cerato: unsure, no confidence in own judgement,
intuition, and seeks approval from others



cherry plum: phobic, fear of being out of control, and
tension



chestnut bud: repeats mistakes, does not learn from
experience



chicory: self-centered, possessive, clingy, demanding,
self pity



clematis: absent minded, dreamy, apathetic, and lack
of connection with reality



crab apple: a ‘‘cleanser’’ for prudishness, self–disgust,
feeling unclean



elm: a sense of being temporarily overwhelmed in
people who are usually capable and in control



gentian: discouraged, doubting, despondent



gorse: feelings of pessimism, accepting defeat



heather: need for company, talks about self, and
concentrates on own problems



holly: jealousy, envy, suspicion, anger, and hatred



honeysuckle: reluctance to enter the present and let
the past go
GALE ENCYCLOPEDIA OF MEDICINE

hornbeam: reluctant to face a new day, weary, can’t
cope (mental fatigue)



impatiens: impatience, always in a hurry, and resentful of constraints



larch: feelings of inadequacy and apprehension, lack
of confidence and will to succeed



mimulus: fearful of specific things, shy, and timid



mustard: beset by ‘‘dark cloud’’ and gloom for no
apparent reason



oak: courageous, persevering, naturally strong but
temporarily overcome by difficulties



olive: for physical and mental renewal, to overcome
exhaustion from problems of long–standing



pine: for self–reproach, always apologizing, assuming guilt



red chestnut: constant worry and concern for others



rock rose: panic, intense alarm, dread, horror



rock water: rigid–minded, self–denial, restriction



scleranthus: indecision, uncertainty, fluctuating
moods



star of Bethlehem: consoling, following shock or
grief or serious news



sweet chestnut: desolation, despair, bleak outlook



vervain: insistent, fanatical, over–enthusiastic



vine: dominating, overbearing, autocratic, tyrannical



walnut: protects during a period of adjustment or
vulnerability



water violet: proud, aloof, reserved, enjoys being
alone



white chestnut: preoccupation with worry, unwanted
thoughts



wild oat: drifting, lack of direction in life



wild rose: apathy, resignation, no point in life



willow bitter: resentful, dissatisfied, feeling life is
unfair

Originally, Bach collected the dew from chosen
flowers by hand to provide his patients with the
required remedy. This became impractical when his
treatment became so popular that production could
not keep up with demand. He then set about finding a
way to manufacture the remedies, and found that
floating the freshly picked petals on the surface of
spring water in a glass bowl and leaving them in strong
sunlight for three hours produced the desired effect.
Therapists explain that the water is ‘‘potentized’’ by
the essence of the flowers. The potentized water can
GALE ENCYCLOPEDIA OF MEDICINE

then be bottled and sold. For more woody specimens,
the procedure is to boil them in a sterilized pan of
water for 30 minutes. These two methods produce
‘‘mother tinctures’’ and the same two methods devised
by Bach are still used today. Flower essences do not
contain any artificial chemical substances, except for
alcohol preservative.
Bach remedies cost around $10 each, and there is
no set time limit for treatment. It may take days,
weeks, or in some cases months. Flower essences cost
around $6 each, and there is also no set time for the
length of treatment, or the amount of essences that
may be taken. These treatments are not generally
covered by medical insurance.

Precautions
Bach remedies and flower essences are not difficult to understand, and are considered suitable for
self administration. The only difficulty may be in
finding the correct remedy, as it can sometimes be
tricky to pinpoint an individual’s emotional disposition. They are even safe for babies, children, and
animals. An important aspect of treatment with
flower remedies, is that if you feel instinctively that
you need a particular remedy, you are encouraged
to act on that instinct. However, it is advisable not to
continue a particular remedy once you feel you
no longer need it, and to try a different one if you
feel that progress is not being made.
The remedies are administered from a stoppered
bottle and need to be diluted. Individuals sensitive
to alcohol can apply the concentrate directly to
temples, wrists, behind the ears, or underarms.
They should be kept in a cool dark place; like this
they should last indefinitely. However, a diluted
remedy should not be kept longer than three weeks.
Two drops of each diluted remedy should be taken
four times a day, including first thing in the morning
and last thing at night. If the rescue remedy is
being used, four drops should be used instead.
Most therapists recommend that they be taken in
spring water, but the remedy can be taken directly
from the bottle, if care is taken that the dropper
does not touch the tongue, as this would introduce
bacteria that would spoil the remedy.
It is not recommended that more than six or seven
Bach remedies be used at any one time. Instead, it is
preferable to divide a larger amount up into two lots
to ensure the optimum effectiveness of the remedies.
No combination, or amount of combinations of the
remedies can cause any harm, rather they become less
effective.
1491

Flower remedies



Fluke infections

ORGANIZATIONS

KEY TERMS
Aura—Emanation of light from living things (plants
and animals) that can be recorded by Kirlian
photography.
Essence—The constituent of a plant that determines
its characteristics.
Potentize—The process of transferring the healing
energy of a plant into spring water.
Window—A perspective adopted to assess the
property of a given plant.

Dr. Edward Bach Centre. Mount Vernon, Bakers Lane,
Sotwell, Oxon, OX10 OPX, UK.
centre@bachcentre.com.
<http://www.bachcentre.com>.
Flower Essence Society. P.O. Box 459, Nevada City, CA
95959. (800) 736-9222 (US & Canada). (53) 265-9163.
Fax: (530) 265-0584. mail@flowersociety.org.
<http://www.flowersociety.org>.

Patricia Skinner

Flu see Influenza
Flucona see Antifungal drugs, systemic

Unlike FES, the Bach Centre does not encourage
research to ‘‘prove’’ that the remedies work, preferring
that people find out for themselves. They strive to keep
the use of the Bach remedies as simple as possible, and
to this end they do not keep case records. Bach warned
before he died that others would try to change
his work and make it more complicated. He was
determined to keep it simple so that anyone could
use it, and that is why he limited the system to only
38 remedies. The Centre points out that many who
have used Bach’s research as a starting point have
added other remedies to the list, even some that Bach
himself rejected.

Side effects
Flower remedies or essences are generally
regarded as being totally safe, and there are no
known side effects apart from the rare appearance of
a slight rash, which is not a reason to discontinue
treatment, says the Bach Centre.

Research and general acceptance
Bach flower remedies and flower essences have not
yet officially won the support of allopathic medicine,
despite the fact that more and more medical doctors are
referring patients for such treatments on the strength of
personal conviction. However, it is difficult to discount
the scores of testimonials. Some practitioners refer
skeptics to the research that has been done regarding
the ‘‘auras’’ of living things. Theoretically, the stronger
the aura, the more alive an organism is. Flower essences
have very strong auras.
Resources
BOOKS

Somerville, R. Flower Remedies. New York: Time-Life
Books.
1492

Fluke infections
Definition
Fluke infections are diseases of the digestive tract
and other organ systems caused by several different
species of parasitic flatworms (Trematodes) that have
complex life cycles involving hosts other than human
beings. Trematode comes from a Greek word that
means having holes and refers to the external suckers
that adult flukes use to draw nourishment from their
hosts. Fluke infections are contracted by eating
uncooked fish, plants, or animals from fluke-infected
waters. Symptoms vary according to the type of fluke
infection.

Description
In humans, fluke infections can be classified
according to those diseases caused by liver flukes
and those caused by lung flukes. Diseases caused by
liver flukes include fascioliasis, opisthorchiasis, and
clonorchiasis. Cases of liver fluke infection have been
reported in Europe and the United States, as well as
the Middle East, China, Japan, and Africa. Diseases
caused by lung flukes include paragonimiasis.
Paragonimiasis is a common infection in the Far East,
Southeast Asia, Africa, Central and South America,
Indonesia, and the Pacific Islands. It is estimated that
between 40 million and 100 million people worldwide
suffer from either liver or lung fluke infections.
In their adult stage, liver and lung flukes are
symmetrical in shape, ranging between 1/4–1 in in
length, and look somewhat like long, plump leaves
or blades of grass. They enter through the mouth
and can infect any person at any age.
GALE ENCYCLOPEDIA OF MEDICINE

Fluke infections

Causes and symptoms
The symptoms of fluke infection differ somewhat
according to the type of fluke involved. All forms of
liver and lung fluke infection, however, have the
following characteristics:


most persons who get infected do not develop symptoms (asymptomatic)



the early symptoms of an acute fluke infection are
not unique to these diseases alone (nonspecific
symptoms)



infection does not confer immunity against re-infection
by the same species or infection by other species of
flukes



infection is usually associated with eating uncooked
fish, plants, or animals that live in fresh water
Fascioliasis

Fascioliasis is caused by Fasciola hepatica, the
sheep liver fluke. The fluke has a three-part life cycle
that begins when eggs from a host’s feces are deposited
in water. The eggs release free-swimming larvae
(miracidia) that infect snails. The snails then release
free-swimming larvae with tails (cercariae) that form
cysts containing larvae in the infective stage (metacercariae) on vegetation growing in fresh water. Humans
become infected when they eat watercress, water
chestnuts, or other plants covered with the encysted
metacercariae.
When a person eats contaminated plants, the
cysts are broken open in the digestive system, and the
metacercariae leave their cysts, pass through the wall
of the intestine, and enter the liver, where they cause
inflammation and destroy tissue. After a period of
10–15 weeks in the liver, the adult flukes move to the
bile ducts and produce eggs. Acute fascioliasis is
marked by abdominal pain with headache, loss of
appetite, anemia, and vomiting. Some patients develop
hives, muscle pains, or a yellow-color to the skin
and whites of the eyes (jaundice). Chronic forms of
the disease may produce complications, including
blockage of the bile ducts or the migration of adult
flukes to other parts of the body.
Opisthorchiasis and clonorchiasis
These infections are caused by Clonorchis sinensis,
the Chinese liver fluke, and Opisthorchis viverrini or
O. felineus. The diseases are widespread, affecting
more than 20 million people in Japan, China,
Southeast Asia, and India. The life cycle of these
liver flukes is similar to that of F. hepatica except
GALE ENCYCLOPEDIA OF MEDICINE

A micrograph of adult intestinal blood flukes, Schistosoma
mansoni. Humans can become infected while bathing or
working in contaminated water. (Photo Researchers, Inc.
Reproduced by permission.)

that the etacercariae are encysted in freshwater fish
rather than on plants. Dogs, cats, and other mammals
that eat raw fish can be infected with opisthorchiasis
and clonorchiasis.
The symptoms of opisthorchiasis and clonorchiasis are similar to those of fascioliasis and include both
acute and chronic forms. In acute infection, the patient
may be tired, have a low-grade fever, pains in the
joints, a swollen liver, abdominal pain, and a skin
rash. The acute syndrome may be difficult to diagnose
because the fluke eggs do not appear in the patient’s
stool for three to four weeks after infection. Patients
with the chronic form of the disease experience a loss
of appetite, fatigue, low-grade fever, diarrhea, and an
enlarged liver that feels sore when the abdomen is
pressed.
Paragonimiasis
Paragonimiasis is caused by a lung fluke, either
Paragonimus westermani or P. skrjabini. These flukes
are larger than liver flukes and infect meat- or fisheating animals as well as humans. Their life cycle is
similar to that of liver flukes except that their encysted
larvae infect crabs and crayfish rather than plants or
fish. Humans can ingest the encysted metacercariae
from drinking contaminated water or eating raw or
undercooked crabs and crayfish.
1493

Fluke infections

In humans, the metacercariae are released from
their cysts in the small intestine and migrate to the
lungs or the brain in 1% of cases. In the lungs, the
flukes lay their eggs and form areas of inflammation
covered with a thin layer of fibrous tissue. These
areas of infection may eventually rupture, causing
the patient to cough up fluke eggs, blood, and
inflamed tissue. The period between the beginning
of the infection and the appearance of the eggs during
coughing is about six weeks. Patients with lung
infections may have chest pain and fever as well as
rust-colored or bloody sputum. Lung infections can
lead to lung abscess, pneumonia, or bronchitis.
Patients with fluke infections of the brain may experience seizures or a fatal inflammation of brain tissue
called encephalitis. Some patients also develop
diarrhea and abdominal pain or lumps under the
skin that contain adult flukes.

Diagnosis
Diagnosis of fluke infections is based on a combination of the patient’s history, particularly travel or
residence in areas known to have flukes, and identification of the fluke’s eggs or adult forms. In some
patients, the eggs are found in fluid from the lungs,
bile duct, or small intestine. Samples of these fluids can
be obtained with a suction instrument (aspirator).
Because most types of fluke infections are rare in the
United States, stool specimens or body fluid samples
may need to be sent to a laboratory with experts in
unusual diseases or conditions to identify the specific
parasite. In some cases, adult flukes may be found in
the patient’s stools, vomit, sputum, or skin lumps (for
lung flukes). In the case of lung flukes, it is important
for the doctor to rule out tuberculosis as a possible
diagnosis. A tuberculosis skin test and chest x ray will
usually be sufficient to do this.
Blood tests may be useful in diagnosing fluke
infections, but their usefulness is limited because of
cross-reactions. A cross-reaction occurs in blood
testing when a particular disease agent reacts with
antibodies specific to another disease agent. This
result means that the doctor may know that the
person is infected by flukes but cannot tell from the
blood test alone which specific type of fluke is causing
the disease. In addition, blood tests for fluke infections cannot distinguish between past and current
infections. In some cases, sophisticated imaging
techniques, such as computed tomography scans (CT
scans) or ultrasound scans of the patient’s chest or
brain (for lung flukes) or abdomen (for liver flukes),
are useful in confirming a diagnosis of fluke
infection.
1494

KEY TERMS
Aspirator—A medical instrument that uses suction
to withdraw fluids from the lungs, digestive tract, or
other parts of the body for laboratory testing.
Asymptomatic—Persons who carry a disease and
are usually capable of transmitting the disease but,
who do not exhibit symptoms of the disease are
said to be asymptomatic.
Cercaria (plural, cercariae)—An intermediatestage of the fluke larva, released into water by
infected snails.
Cross-reaction—A reaction that occurs in blood
testing when a disease agent reacts to the specific
antibody for another disease agent. Cross-reactions
are common in blood tests for fluke infections
because the different species are closely related.
Encysted—Enclosed in a cyst or capsule. Flukes
spend part of their life cycle as encysted larvae.
Fluke—A parasitic flatworm that has external suckers. Flukes are sometimes called trematodes.
Host—The living animal that supplies nutrition to a
parasite.
Jaundice—Yellowing of the skin and the whites of
the eyes as a result of excess bile in the blood due to
an improperly functioning liver.
Metacercaria
(plural,
metacercariae)—The
encysted stage of a fluke larva that produces infection in human beings.
Miracidium (plural, miracidia)—The freeswimming larval form in the life cycle of the liver
fluke.
Parasite—An organism that lives on or inside an
animal of a different species and feeds on it or
draws nutrients from it.
Trematode—Parasitic flatworms or another name
for fluke, taken from a Greek word that means
having holes.

Treatment
Liver and lung fluke infections are treated with
medications. These include triclabendazole, praziquantel, bithionol, albendazole, and mebendazole.
Praziquantel works by paralyzing the flukes’ suckers,
forcing them to drop away from the walls of the
host’s blood vessels. In the United States, bithionol is
available only from the Centers for Disease Control
(CDC). Depending on the species of fluke and the
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The prognosis for recovery from liver fluke infections is good, although patients with serious infections
may be more vulnerable to other diseases, particularly
if significant liver damage has occurred. Most patients
with lung fluke infections also recover, however, severe
infections of the brain can cause death from the destruction of central nervous system or brain tissue.

Prevention
No vaccines have been developed that are effective against lung or liver fluke infections. Prevention of
these infections includes the following measures:


boiling or purifying drinking water



avoiding raw or undercooked fish or salads made
from fresh aquatic plants; all food eaten in areas
with fluke infestations should be cooked thoroughly;
pickling or smoking will not kill fluke cysts in fish or
shellfish



control or eradication of the snails that serve as the
flukes’ intermediate hosts

Resources

Physicians prescribe these drugs for bacterial infections in many parts of the body. For example, they
are used to treat bone and joint infections, skin
infections, urinary tract infections, inflammation of
the prostate, serious ear infections, bronchitis,
pneumonia, tuberculosis, some sexually transmitted
diseases (STDs), and some infections that affect people
with AIDS.

Description
Fluoroquinolones are available only with a
physician’s prescription and are sold in tablet and
injectable forms. Examples of these medicines are
moxifloxacin (Avelox), ciprofloxacin (Cipro), ofloxacin (Floxin), levofloxacin (Levaquin), lomefloxacin
(Maxaquin), norfloxacin (Noroxin), enoxacin
(Penetrex), gatifloxacin (Tequin), and sparfloxacin
(Zagam).
In the wake of the anthrax terrorist attacks in the
United States in 2001, ciprofloxacin received extensive
media attention because it was the only drug labeled as
approved by the Food and Drug Administration
(FDA) for both prophylaxis and treatment of inhalation anthrax (the most serious form of the disease).
However, in late October 2001, the FDA issued a
notice clarifying that the antibiotic doxycycline is
also approved for anthrax prophylaxis and that
doxycycline and amoxicillin are also approved for
treatment for all forms of anthrax. The FDA encouraged companies to update labeling of these products
with this previously unspecified information.

BOOKS

Goldsmith, Robert S. ‘‘Infectious Diseases: Protozoal &
Helminthic.’’ Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Fluoroquinolones
Definition
Fluoroquinolones are medicines that kill bacteria
or prevent their growth.

Purpose
Fluoroquinolones are antimicrobials, medicines
used to treat infections caused by microorganisms.
GALE ENCYCLOPEDIA OF MEDICINE

Recommended dosage
The recommended dosage depends on the type
and strength of fluoroquinolone, and the kind of
infection for which it is being taken. Check with the
physician who prescribed the drug or the pharmacist
who filled the prescription for the correct dosage.
To make sure the infection clears up completely,
take the medicine for as long as it has been prescribed.
Do not stop taking the drug just because symptoms
begin to improve. Symptoms may return if the drug is
stopped too soon.
Fluoroquinolones work best when they are at
constant levels in the blood. To help keep levels
constant, take the medicine in doses spaced evenly
through the day and night. Do not miss any doses.
For best results, take this medicine with a full glass of
water and drink several more glasses throughout the
day, every day during treatment with the drug. The
extra water will help prevent some side effects. Some
1495

Fluoroquinolones

severity of infection, the course of treatment can vary
from several days to several weeks. Cure rates vary
from 50–95%. Most patients experience mild temporary side effects from these drugs, including diarrhea,
dizziness, or headache.

Fluoroquinolones

fluoroquinolones should be taken on an empty stomach; others may be taken with meals. Check package
directions or ask the physician or pharmacist for
instructions on how to take the medicine.

Precautions
An important precaution for any antibiotic is that
unnecessary use or abuse of antibiotics can encourage
drug-resistant strains of bacteria to develop and
proliferate. These drug-resistant strains then become
difficult, or even impossible, to treat. Bacteria found in
hospitals appear to have become especially resilient,
and are causing increasing difficulty for patients and
the doctors treating them. Following the U.S. 2001
anthrax attacks, for example, the American Medical
Association urged its members not to prescribe
ciprofloxacin unnecessarily. One fear is that the
overuse of the drug could reduce its effectiveness
against infections such as typhoid fever, hospitalacquired pneumonia, and others.
Research suggests that fluoroquinolones may
cause bone development problems in children and
teenagers. Infants, children, teenagers, pregnant
women, and women who are breastfeeding should
not take this medicine unless directed to do so by a
physician.
Although such side effects are rare, some people
have had severe and life-threatening reactions to
fluoroquinolones. Call a physician immediately if
any of these signs of a dangerous reaction occur:


swelling of the face and throat



swallowing problems



shortness of breath



rapid heartbeat



tingling of fingers or toes



itching or hives



loss of consciousness

anything else that might be dangerous until they
have found out how the drugs affect them.
This medicine may increase sensitivity to sunlight.
Even brief exposure to sun can cause a severe sunburn
or a rash. While being treated with fluoroquinolones,
avoid being in direct sunlight, especially between
10 a.m. and 3 p.m.; wear a hat and tightly woven
clothing that covers the arms and legs; use a sunscreen
with a skin protection factor (SPF) of at least 15;
protect the lips with a sun block lipstick; and do not
use tanning beds, tanning booths, or sunlamps.
Do not take antacids that contain aluminum,
calcium, or magnesium at the same time as fluoroquinolones. The antacids may keep the fluoroquinolones
from working as they should. If antacids are needed,
take them at least two hours before or two hours after
taking norfloxacin or ofloxacin, at least four hours
before or two hours after taking ciprofloxacin.
Follow the same instructions for taking sucralfate
(Carafate), a medicine used to treat stomach ulcers
and other irritation in the digestive tract and mouth.
Anyone who has had unusual reactions to fluoroquinolones or related medicines such as cinoxacin
(Cinobac) or nalidixic acid (NegGram) in the past
should let his or her physician know before taking
the drugs again. The physician should also be told
about any allergies to foods, dyes, preservatives, or
other substances.
Before using fluoroquinolones, people with any
of these medical problems should make sure their
physicians are aware of their conditions:


kidney disease



liver disease with kidney disease



diseases of the brain or spinal cord, including hardening of the arteries in the brain, epilepsy, and other
seizure disorders

Taking fluoroquinolones with certain other drugs
may affect the way the drugs work or may increase the
chance of side effects.

Some fluoroquinolones may weaken the tendons
in the shoulder, hand, or heel, making the tendons
more likely to tear. Anyone who notices pain or
inflammation in these or other tendon areas should
stop taking the medicine immediately and call a physician. Rest and avoid exercise until the physician
determines whether the tendons are damaged. If the
tendons are torn, surgery may be necessary to repair
them.

The most common side effects are mild diarrhea,
nausea, vomiting, stomach or abdominal pain, dizziness, drowsiness, lightheadedness, nervousness, sleep
problems, and headache. These problems usually go
away as the body adjusts to the drug and do not
require medical treatment unless they are bothersome.

These medicines make some people feel drowsy,
dizzy, lightheaded, or less alert. Anyone who takes
these drugs should not drive, use machines or do

More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with a physician immediately:

1496

Side effects

GALE ENCYCLOPEDIA OF MEDICINE

skin rash or other skin problems such as itching,
peeling, hives, or redness



fever



agitation or confusion



hallucinations



shakiness or tremors



seizures or convulsions



tingling of fingers or toes



pain where the medicine was injected (lasting after
the injection)



pain in the calves, spreading to the heels



swelling of the calves or lower legs



swelling of the face or neck



swallowing problems



rapid heartbeat



shortness of breath



loss of consciousness

Other rare side effects may occur. Anyone who
has unusual symptoms after taking fluoroquinolones
should get in touch with his or her physician.

Interactions
Fluoroquinolones may interact with other medicines. When this happens, the effects of one or both of
the drugs may change or the risk of side effects may be
greater. Anyone who takes fluoroquinolones should
let the physician know all other medicines he or she
is taking. Among the drugs that may interact with
fluoroquinolones are:


antacids that contain aluminum, calcium, or
magnesium



medicines that contain iron or zinc, including multivitamin and mineral supplements



sucralfate (Carafate)



caffeine



blood thinning drugs such as warfarin (Coumadin)



airway opening drugs (bronchodilators) such as
aminophylline, theophylline (Theo-Dur and other
brands), and oxtriphylline (choledyl and other brands)



didanosine (Videx), used to treat HIV infection.

The list above does not include every drug that
may interact with fluoroquinolones. Be sure to check
with a physician or pharmacist before combining
fluoroquinolones with any other prescription or
nonprescription (over-the-counter) medicine.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Bronchitis—Inflammation of the air passages of the
lungs.
Digestive tract—The stomach, intestines, and
other parts of the body through which food passes.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Microorganism—An organism that is too small to
be seen with the naked eye.
Pneumonia—A disease in which the lungs become
inflamed. Pneumonia may be caused by bacteria,
viruses, or other organisms, or by physical or chemical irritants.
Prostate—A donut-shaped gland in males below
the bladder that contributes to the production of
semen.
Sexually transmitted disease (STD)—A disease that
is passed from one person to another through sexual intercourse or other intimate sexual contact.
Tendon—A tough band of tissue that connects muscle to bone.
Tuberculosis—An infectious disease that usually
affects the lungs, but may also affect other parts of
the body. Symptoms include fever, weight loss, and
coughing up blood.
Urinary tract—The passage through which urine
flows from the kidneys out of the body.

Resources
OTHER

‘‘Fluoroquinolones (Systemic).’’ National Library of medicine. <http://www.nlm.nih.gov/medlineplus/druginfo/
fluoroquinolonessystemic202656.html>.

Rosalyn Carson-DeWitt, MD

Fluoxetine see Selective serotonin reuptake
inhibitors
Flurbiprofen see Nonsteroidal
anti-inflammatory drugs
Focal glomeruloscle see Nephrotic
syndrome
1497

Fluoroquinolones



Folic acid

Folic acid
Definition
Folic acid is a water-soluable vitamin belonging to
the B-complex group of vitamins. These vitamins help
the body break down complex carbohydrates into
simple sugars to be used for energy. Excess B vitamins
are excreted from the body rather than stored for later
use. This is why sufficient daily intake of folic acid is
necessary.

Description
Folic acid is also known as folate, or folacin. It is
one of the nutrients most often found to be deficient in
the Western diet, and there is evidence that deficiency
is a problem on a worldwide scale. Folic acid is found
in leafy green vegetables, beans, peas and lentils, liver,
beets, brussel sprouts, poultry, nutritional yeast, tuna,
wheat germ, mushrooms, oranges, asparagus, broccoli, spinach, bananas, strawberries, and cantaloupes.
In 1998, the U.S. Food and Drug Administration
(FDA) required food manufacturers to add folic acid
to enriched bread and grain products to boost intake
and to help prevent neural tube defects (NTD).

Purpose
Folic acid works together with vitamin B12 and
vitamin C to metabolize protein in the body. It is
important for the formation of red and white blood
cells. It is necessary for the proper differentiation and
growth of cells and for the development of the fetus. It
is also used to form the nucleic acid of DNA and
RNA. It increases the appetite and stimulates the
production of stomach acid for digestion and it aids
in maintaining a healthy liver. A deficiency of folic
acid may lead to anemia, in which there is decreased
production of red blood cells. This reduces the
amounts of oxygen and nutrients that are able to get
to the tissues. Symptoms may include fatigue, reduced
secretion of digestive acids, confusion, and forgetfulness. During pregnancy, a folic acid deficiency may
lead to preeclampsia, premature birth, and increased
bleeding after birth.
People who are at high risk of strokes and heart
disease may greatly benefit by taking folic acid supplements. An elevated blood level of the amino acid
homocysteine has been identified as a risk factor for
some of these diseases. High levels of homocysteine
have also been found to contribute to problems with
osteoporosis. Folic acid, together with vitamins B6 and
1498

B12, helps break down homocysteine, and may help
reverse the problems associated with elevated levels.
Pregnant women have an increased need for folic
acid, both for themselves and their child. Folic acid is
necessary for the proper growth and development of
the fetus. Adequate intake of folic acid is vital for the
prevention of several types of birth defects, particularly NTDs. The neural tube of the embryo develops
into the brain, spinal cord, spinal column, and the
skull. If this tube forms incompletely during the first
few months of pregnancy a serious, and often fatal,
defect results in spina bifida or anencephaly. Folic
acid, taken from one year to one month before conception through the first four months of pregnancy,
can reduce the risk of NTDs by 50–70%. It also helps
prevent a cleft lip and palate.
Research shows that folic acid can be used to
successfully treat cervical dysplasia, a condition diagnosed by a Pap smear, of having abnormal cells in the
cervix. This condition is considered to be a possible
precursor to cervical cancer, and is diagnosed as an
abnormal Pap smear. Daily consumption of 1,000 mcg
of folic acid for three or more months has resulted in
improved cervical cells upon repeat Pap smears.
Studies suggest that long-term use of folic acid
supplements may also help prevent lung and colon
cancer. Researchers have also found that alcoholics
who have low folic acid levels face a greatly increased
possibility of developing colon cancer.

Preparations
To correct a folic acid deficiency, supplements are
taken in addition to food. Since the functioning of the
B vitamins is interrelated, it is generally recommended
that the appropriate dose of B-complex vitamins be
taken in place of single B vitamin supplements. The
Recommended Dietary Allowances (RDA) for folate
is 400 mcg per day for adults, 600 mcg per day for
pregnant women, and 500 mcg for nursing women.
Medicinal dosages of up to 1,000-2,000 mcg per day
may be prescribed.

Precautions
Folic acid is not stable. It is easily destroyed by
exposure to light, air, water, and cooking. Therefore,
the supplement should be stored in a dark container in
a cold, dry place, such as a refrigerator. Many medications interfere with the body’s absorption and use of
folic acid. This includes sulfa drugs, sleeping pills,
estrogen, anti-convulsants, birth control pills, antacids, quinine, and some antibiotics. Using large
GALE ENCYCLOPEDIA OF MEDICINE

Homocysteine—An amino aid involved in the
breakdown and absorption of protein in the body.
Preeclampsia—A serious disorder of late pregnancy in which the blood pressure rises, there is a
large amount of retained fluids, and the kidneys
become less effective and excrete proteins directly
into the urine.
Raynaud’s disease—A symptom of various underlying conditions affecting blood circulation in the
fingers and toes and causing them to be sensitive to
cold.
Recommended Dietary Allowance (RDA)—
Guidelines for the amounts of vitamins and minerals
necessary for proper health and nutrition established
by the National Academy of Sciences in 1989.
Water-soluble vitamins—Vitamins that are not
stored in the body and are easily excreted. They
must, therefore, be consumed regularly as foods or
supplements to maintain health.

amounts of folic acid (e.g., over 5,000 mcg per day) can
mask a vitamin B12 deficiency and thereby risk of
irreversible nerve damage.

Side effects
At levels of 5,000 mcg or less, folic acid is generally
safe for use. Side effects are uncommon. However,
large doses may cause nausea, decreased appetite,
bloating, gas, decreased ability to concentrate, and
insomnia. Large doses may also decrease the effects
of phenytoin (Dilantin), a seizure medication.

Interactions
As with all B-complex vitamins, it is best to take
folic acid with the other B vitamins. Vitamin C is
important to the absorption and functioning of folic
acid in the body.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
OTHER

Adams, Suzanne L. The Art of Cytology: Folic Acid/ B-12
Deficiency. suzann@concetric.net. <http://
www.concentric.net/Suza2/page22.htm>.
GALE ENCYCLOPEDIA OF MEDICINE

Patience Paradox

Folic acid deficiency anemia
Definition
Folic acid deficiency, an abnormally low level of
one of the B vitamins, results in anemia characterized
by red blood cells that are large in size but few in
number.

Description
Folic acid is necessary for growth and cellular
repair, since it is a critical component of DNA and
RNA as well as essential for the formation and
maturation of red blood cells. Folic acid deficiency is
one of the most common of all vitamin deficiencies.
Although it occurs in both males and females, folic
acid deficiency anemia most often affects women over
age 30. It becomes increasingly common as age
impedes the body’s ability to absorb folic acid, a
water-soluble vitamin that is manufactured by intestinal bacteria and stored for a short time in the liver.
Folic acid deficiency has also been implicated as a
cause of neural tube defects in the developing fetus.
Recent research has shown that adequate amounts of
folic acid can prevent up to one-half of these birth
defects, if women start taking folic acid supplements
shortly before conception. Research from China in
2004 showed that women who were low in B vitamins
and folate before conception, though not technically
anemic, still had increased risk of lower birth weight
babies and adverse pregnancy outcome.
A healthy adult needs at least 400 mcg of folic acid
every day. Requirements at least double during pregnancy, and increase by 50% when a woman is breastfeeding. The average American diet, high in fats,
sugar, and white flour, provides about 200 mcg of
1499

Folic acid deficiency anemia

KEY TERMS

‘‘Folic Acid: Coming to A Grocery Store Near You.’’
<http://www.mayohealth.org/mayo/9710/htm/
folic.htm>.
‘‘Folic Acid.’’ <http://www.cybervitamins.com/
folicacid.htm>.
‘‘Folic acid (oral/injectible).’’ Dr. Koop.com.Inc. 700 N.
Mopac, Suite 400, Austin, TX 48731. <http://
www.drkoop.com/hcr/drugstore/pharmacy/leaflets/
english/d00241a1.asp>.
Pregnancy and Nutrition Update. <http://www.mayohealth.org/mayo/9601/htm/pregvit.htm>.

Folic acid deficiency anemia

folic acid, approximately the amount needed to maintain tissue stores of the substance for six to nine
months before a deficiency develops. Most of the
folic acid in foods (with the exception of the folic
acid added to enriched flour and breakfast cereals)
occurs as folate. Folate is only about pne-half as available for the body to use as is the folic acid in pills and
supplements. Folate also is easily destroyed by sunlight, overcooking, or the storing of foods at room
temperature for an extended period of time.
Good dietary sources of folate include:

Diagnosis
Diagnostic procedures include blood tests to measure hemoglobin, an iron-containing compound that
carries oxygen to cells throughout the body.
Symptoms may be reevaluated after the patient has
taken prescription folic acid supplements.

Treatment
Folic acid supplements are usually prescribed, and
self-care includes avoiding:



leafy green vegetables



alcohol



liver





mushrooms

non-herbal tea, antacids, and phosphates (contained
in beer, ice cream, and soft drinks), which restrict
iron absorption



oatmeal



tobacco



peanut butter



red beans



soy



wheat germ

A person with folic acid deficiency anemia should
rest as often as necessary until restored energy levels
make it possible to resume regular activities. A doctor
should be seen if fever, chills, muscle aches, or new
symptoms develop during treatment, or if symptoms
do not improve after two weeks of treatment.

Causes and symptoms
This condition usually results from a diet lacking
in foods with high folic acid content, or from the
body’s inability to digest foods or absorb foods having
high folic acid content. Other factors that increase the
risk of developing folic acid deficiency anemia are:


age



alcoholism



birth control pills, anticonvulsant therapy, sulfa antibiotics, and certain other medications



illness



smoking



stress

Fatigue is often the first sign of folic acid deficiency anemia. Other symptoms include:


anorexia nervosa



pale skin



paranoia



rapid heart beat



sore, inflamed tongue



weakness



weight loss

1500

Alternative treatment
Alternative therapies for folic acid deficiency anemia may include reflexology concentrated on areas
that influence the liver and spleen. Increasing consumption of foods high in folate is helpful. Eating a
mixture of yogurt (8 oz) and turmeric (1 tsp) also may
help resolve symptoms. A physician should be contacted if the tongue becomes slick or smooth or the
patient:


bruises or tires easily



feels ill for more than five days



feels weak or out of breath



looks pale or jaundiced

Prognosis
Although adequate folic acid intake usually cures
this condition in about three weeks, folic acid deficiency anemia can make patients infertile or more
susceptible to infection. Severe deficiencies can result
in congestive heart failure.

Prevention
Eating raw or lightly cooked vegetables every day
will help maintain normal folic acid levels, as will
taking a folic acid supplement containing at least
GALE ENCYCLOPEDIA OF MEDICINE

abnormal tissue growth on one or more of the
hormone-secreting (endocrine) glands (called multiple
endocrine neoplasia), or to diagnose other disorders.

Description
The FSH test is a blood test. Blood will be drawn
from the patient and analyzed in a laboratory.

Resources
PERIODICALS

Ronnenberg, Alayne G., et al. ‘‘IPreceonception
Hemoglobin and Ferritin Concentrations Are
Associated With Pregnancy Outcome in a Prospective
Cohort of Chinese Women.’’ The Journal of Nutrition
October 2004: 2586–2592.

Maureen Haggerty
Teresa G. Odle

Preparation
In preparation for the test, there are no food or
fluid intake restrictions. Patients may be advised to
discontinue certain medications for 48 hours before
the test. A menstruating woman having hot flashes or
irregular periods should be tested on the second or
third day of her menstrual cycle. A woman who has
missed a period and is having other menopausal symptoms can be tested at any time.

Aftercare

Follicle-stimulating hormone
test
Definition
The follicle-stimulating hormone (FSH) test measures the amount of FSH in the blood. FSH is a
hormone that regulates the growth and development
of eggs and sperm, and this test is used to diagnose or
evaluate disorders involving the pituitary gland and
reproductive system.

Purpose
FSH testing is performed if a physician suspects
the patient may have a disorder involving the reproductive system or pituitary gland. The pituitary gland
produces FSH, which stimulates the growth of the
sacks (follicles) that surround the eggs in a woman’s
ovaries. This is important for the process of ovulation,
in which the egg is released. In men, FSH stimulates
production of sperm. If there are abnormal levels of
FSH in the blood it may mean that one of several
disorders are present. Normal fluctuations occur as a
result of puberty, the menstrual cycle, pregnancy, and
menopause.
The FSH test is performed more often on women
than on men. In women, it is used to determine if
menopause has begun, to diagnose infertility and menstrual disorders (such as anovulatory bleeding), to
measure hormone levels in children who enter puberty
at an early age, and to diagnose other disorders. In
men, it can be used to determine early puberty,
GALE ENCYCLOPEDIA OF MEDICINE

No aftercare is necessary.

Risks
There are no risks associated with this test.

Normal results
Normal FSH test results vary according to age and
sexual maturity. The phase of a woman’s menstrual
cycle or use of birth-control pills also affects test results.
For an adult male, normal results range from
about 4–25 units of FSH in every liter of blood (U/L)
or about 5–20 micro-international units in every
milliliter.
For a premenopausal woman, normal values
range from 4–30 U/L or 5–20 micro-international
units per milliliter. In a pregnant woman, FSH levels
are too low to measure. After menopause, normal
values range from 40–250 U/L or 50–100 microinternational units per milliliter.
FSH levels fluctuate during premenopause. If no
other symptoms are present, an elevated FSH level
should not be interpreted as proof that menopause
has begun.

Abnormal results
Anorexia nervosa and disorders of the hypothalamus or pituitary gland can result in abnormally low
FSH levels.
1501

Follicle-stimulating hormone test

400 mcg of this vitamin. Because folic acid deficiency
can cause birth defects, all women of childbearing age
who can become pregnant should consume at least 400
mcg of folic acid daily; a woman who is pregnant
should have regular medical checkups, and take a
good prenatal vitamin.

Folliculitis

Description

KEY TERMS
Anovulatory bleeding—Bleeding without release
of an egg from an ovary.
Hypopituitarism—Underactivity of the pituitary
gland.
Hypothalamus—The part of the brain that controls
the endocrine system.
Klinefelter’s syndrome—Chromosomal abnormality characterized by small testes and male infertility.
Multiple endocrine neoplasia—Abnormal tissue
growth on one or more of the endocrine (hormonesecreting) glands.
Polycystic ovary disease—A condition in which a
woman has little or no menstruation, is infertile, has
excessive body hair, and is obese. The ovaries may
contain several cysts.
Turner syndrome—Chromosomal abnormality characterized by immature reproductive organs in women.

Abnormal levels can also indicate:


infertility



hypopituitarism



klinefelter syndrome (in men)



turner syndrome



ovarian failure



polycystic ovary syndrome

Folliculitis can affect both women and men at any
age. It can develop on any part of the body, but is most
likely to occur on the scalp, face, or parts of the arms,
armpits, or legs not usually covered by clothing.
Small, yellowish-white blister-like lumps (pustules) surrounded by narrow red rings are usually present with both bacterial folliculitis and fungal
folliculitis. Hair can grow through or alongside of
the pustules, which sometimes ooze blood-stained pus.
Folliculitis can cause boils and, in rare instances,
serious skin infections. Bacteria from folliculitis can
enter the blood stream and travel to other parts of the
body.

Causes and symptoms
Folliculitis develops when bacteria, such as
Staphylococcus, or a fungus enters the body through
a cut, scrape, surgical incision, or other break in the
skin near a hair follicle. Scratching the affected area
can trap fungus or bacteria under the fingernails and
spread the infection to hair follicles on other parts of
the body.
The bacteria that cause folliculitis are contagious.
A person who has folliculitis can infect others who live
in the same household.
Factors that increase the risk of developing folliculitis include:


dermatitis



diabetes

Resources



dirty, crowded living conditions

OTHER



eczema

‘‘Follicle-Stimulating Hormone Test.’’Health Answers.com
February 25, 1998. <http://www.healthanswers.com>.



exposure to hot, humid temperatures



infection in the nose or other recent illness



tight clothing

Maureen Haggerty

Follicular cysts see Ovarian cysts

Diagnosis
Diagnosis is based on the patient’s medical history
and observations. Laboratory analysis of the substance drained from a pustule can be used to distinguish bacterial folliculitis from fungal folliculitis.

Folliculitis
Definition
Folliculitis is inflammation or infection of one
or more hair follicles (openings in the skin that
enclose hair).
1502

Treatment
Bacterial folliculitis may disappear without treatment, but is likely to recur. Non-prescription topical
antibiotics like Bacitracin, Mycitracin, or Neomycin,
gently rubbed on to affected areas three or four times a
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
If properly treated, the symptoms of bacterial
folliculitis generally disappear in about two weeks.
Fungal folliculitis should clear up within six weeks.
But it can worsen if the condition is misdiagnosed and
inappropriately treated with steroid creams.

Prevention

Acne folliculitis. (Custom Medical Stock Photo. Reproduced by
permission.)

day, can clear up a small number of bacterial folliculitis pustules. Oral antibiotics such as erythromycin
(Erythocin) may be prescribed if the infection is widespread. The drug griseofulvin (Fulvicin) and topical
antifungal medications are used to treat fungal
folliculitis.
A doctor should be notified if:


pustules spread after treatment has begun or reappear after treatment is completed



the patient’s fever climbs above 100 8F (37.8 8C)



the patient develops boils or swollen ankles



redness, swelling, warmth, or pain indicate that the
infection has spread



unexplained new symptoms appear

Alternative treatment
Eating a balanced diet, including protein, complex
carbohydrates, healthy fats, fresh fruits and vegetables, and drinking eight to 10 glasses of water a day
may stimulate the body’s immune system and shorten
the course of the infection. Garlic (Allium sativum) and
goldenseal (Hydrastis canadensis), both antiseptic
agents against staph infections, may be taken. The
daily dosage would vary from person to person and
is based on the severity of the infection. Echinacea
(Echinacea spp.) is helpful in modulating immune
function. Again, the dosage would vary.
GALE ENCYCLOPEDIA OF MEDICINE

Anyone who has a tendency to develop folliculitis
should cleanse the skin with antibacterial soap twice a
day and before shaving and should not use oily skin
lotions. Men should not shave while the beard area is
infected. When they begin shaving again, they should
use a new blade each time. Women who have had
fungal folliculitis should use depilatory creams instead
of razors. Daily shampooing can help prevent folliculitis in the scalp. The spread of infection can be prevented by not sharing towels or washcloths.
Resources
OTHER

‘‘Folliculitis.’’ Thrive Online. April 5, 1998. <http://
thriveonline.oxygen.com>.

Maureen Haggerty

Food allergies
Definition
Food allergies are the body’s abnormal responses
to harmless foods; the reactions are caused by the
immune system’s reaction to some food proteins.

Description
Food allergies are often confused with food intolerance. However, the two conditions have different
causes and produce different symptoms. A food
allergy is also known as food hypersensitivity. The
allergy is caused when a person eats something that
the immune system incorrectly identifies as harmful.
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Food allergies

Daily doses of 30–50 mg zinc and 1,000–5,000 mg
Vitamin C (taken in equal amounts at several times
during the day), and 300–2,000 mg bioflavinoids can
also strengthen the body’s infection-fighting ability.
High doses of vitamins and minerals should not be
used without a doctor’s approval.

Food allergies

Food allergies
About 4% of adults have food allergies according
to the National Institute of Allergy and Infectious
Diseases (NIAID). The condition affects approximately 6 to 8% of children age 4 and younger.
The immune system works to protect the body
and creates food-specific antibodies. The antibodies
are proteins that battle antigens, substances that are
foreign or initially outside the body. The introduction
of an antigen produces the immune response.
Antibodies are created to destroy the antigen or counteract its effectiveness.
The food that triggered that reaction is called an
allergen. The antibodies are like an alarm system
coded to detect the food regarded as harmful. The
next time the person eats that food, the immune system discharges a large amount of histamine and chemicals. This process meant to protect the body against
the allergen causes an allergic reaction that can affect
the respiratory tract, digestive tract, skin, and cardiovascular system.
Allergic reactions can occur in minutes or in up to
two hours after the person ate the food. Symptoms
include swelling of the tongue, diarrhea, and hives. In
severe cases, the allergic reaction can be fatal. The
most severe reaction is anaphylaxis, which could be
life-threatening.
Food intolerance
While food allergies involve the immune system,
food intolerance is not related to the immune system.
For example, a person who is lactose intolerant has a
shortage of lactose, the digestive enzyme that breaks
down the sugar in milk and dairy products. That
person could experience stomach pain or bloating several hours after drinking milk.
People who are food-intolerant can sometimes
consume that food and not experience intolerance
symptoms. Those diagnosed with food allergies must
avoid the foods that produce the allergic reactions.

Approximately 0.4% of Americans have allergic reactions to tree nuts.
Food allergy demographics
Most children have allergies to eggs, milk, peanuts or tree nuts, and soy, according to the American
Dietetic Association (ADA). The young generally outgrow their allergies. They are more likely to outgrow
milk and soy allergies, according to NIAID. However,
children and adults usually allergic to peanuts and tree
nuts for life. The most frequent causes of food allergies
in adulthood are peanuts, tree nuts, fish, and shellfish.
Allergies are hereditary. There is a tendency for
the immune system to create IgE antibodies in people
with family histories of allergies and allergic conditions like hay fever and asthma, according to NIAID.
The likelihood of a child having food allergies
increases when both parents are allergic.
Furthermore, people are allergic to the foods that
are eaten frequently in their countries. A rice allergy is
more common in Japan, and codfish allergies occur
more in Scandinavian countries, according to NIAID.

Causes and symptoms
Food allergies are caused by the immune system’s
reaction to a food item that it believes is harmful.
When the food is digested, the immune system
responds by creating immunoglobulin E (IgE) antibodies as a defense. The antibodies are proteins
found in the bloodstream. Formed to protect the
body against harmful substances, the antibodies are
created after the person’s first exposure to the allergen.
The majority of food allergies are caused by foods
in eight families. In some families, every food causes
an allergic reaction. In other families like shellfish, a
person may be allergic to one species, but able to eat
others. The allergy-inducing foods include:


Milk. The dairy family includes milk, ice cream,
yogurt, butter, and some margarines. Nondairy
foods that contain casein must be avoided.
Prepared foods that contain milk range from breads
and doughnuts to sausage and soup, according to
the ADA.



Eggs. Although a person may be allergic to either the
egg white or yolk, the entire egg must be avoided
because there is a risk of cross-contamination. Eggs
are an ingredient in mayonnaise. Moreover, products such as baked goods, breads, pasta, yogurt,
and batter on fried foods may contain eggs. In addition, some egg-substitute products contain
egg whites.

Allergy-producing foods
Although approximately 160 foods produce allergic reactions, approximately 90% of reactions are
caused by some or all items within eight food families.
These are milk, eggs, peanuts, tree nuts, fish, shellfish,
wheat, and soy. These foods can cause severe reactions. The most adverse reactions are caused by peanuts and tree nuts. According to NIAID, about 0.6%
of Americans are impacted by peanut allergies.
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GALE ENCYCLOPEDIA OF MEDICINE



Peanuts grow in the ground and are legumes like
lentils and chickpeas. A person with a peanut allergy
may not be allergic to other legumes or tree nuts.
Products to be avoided include peanuts, peanut butter, peanut oil, and some desserts and candy. In
addition, some Asian dishes are prepared with a peanut sauce. Tree nuts include almonds, cashews,
pecans, walnuts, Brazil nuts, chestnuts, hazelnuts,
macadamia nuts, pine nuts, pistachios, and hickory
nuts. Products containing tree nuts include nut oil,
nut oil, desserts, candy, crackers, and barbecue
sauce. A person may be allergic to one type of nut
but able to eat other nuts. That should be determined
after consulting with a doctor.
Fish allergy is generally diagnosed as an allergy to all
fish species because the allergen is similar among the
different species.



Shellfish species include lobster, crab, shrimp, clams,
oysters, scallops, mollusks, and crawfish. An allergy
to one type of shellfish may indicate an allergy to
others.



Wheat is a grain found in numerous foods including
breads, cereals, pastas, lunch meats, desserts, and
bulgar. It is also found in products such as enriched
flour and farina.



Soy. The soybean is a legume, and people who have
this allergy are rarely allergic to peanuts or other
legumes. Soy is an ingredient in many processed
foods including crackers and baked goods, sauces,
and soups. There is also soy in canned tuna, according to the ADA.
The chemical reaction

During the initial exposure, many IgE antibodies
are created. These attach to mast cells. These cells are
located in tissue throughout the body, especially in
areas such as the nose, throat, lungs, skin, and gastrointestinal tract. These are also the areas where allergic
reactions occur.
The antibodies are in place, and a reaction is
triggered the next time the person eats the food
regarded as harmful. As the allergen reacts with the
IgE, the body releases histamine and other chemicals.
Histamine is a chemical located in the body’s cells.
When released during an allergic reaction, histamine and other chemicals cause symptoms like
inflammation.
The type of allergic reaction depends on where the
antibodies are released, according to NIAID.
Chemicals released in the ears, nose, and throat
could cause the mouth to itch. The person may also
GALE ENCYCLOPEDIA OF MEDICINE

have difficulty breathing or swallowing. If the allergen
triggers a reaction in the gastrointestinal tract, the
person could experience stomach pain or diarrhea.
An allergic reaction that affects skin cells could produce hives. This condition also known as urticaria is
an allergic reaction characterized by itching, swelling,
and the presence of patchy red areas called wheals.
Severe allergic reaction
Anaphylaxis is a severe allergic reaction that is
potentially life-threatening. Also known as an anaphylactic reaction, this condition requires immediate
medical attention. The reaction occurs within seconds
or up to several hours after the person ate the allergyinducing food.
Symptoms can include difficulty breathing, a
tingling feeling in the mouth, and a swelling in the
tongue and throat. The person may experience hives,
vomiting, abdominal cramps, and diarrhea. There is
also a sudden drop in blood pressure. Anaphylaxis
could be fatal if not treated promptly.
Each year, some 150 Americans die from foodinduced anaphylaxism, according to NIAID. The
casualties are generally adolescents and young adults.
The risk increases for people who have allergies and
asthma. Also at increased risk are people who experienced previous episodes of a naphylaxis.
The peanut is one of the primary foods that trigger
an anaphylactic reaction. Tree nuts also cause the
reaction. The nuts generally linked to anaphylaxis
are almonds, Brazil nuts, cashews, chestnuts, hazelnuts, macadamia nuts, pecans, pine nuts, pistachios
and walnuts. Fish, shellfish, and eggs can also set off
the reaction, according to the ADA.
Cross-reactivity
Cross-reactivity is the tendency of a person with
one allergy to reaction to another allergen. A person
allergic to crab might also be allergic to shrimp. In
addition, someone with ragweed sensitivity could
experience sensations when trying to eat melons during ragweed pollinating season, according to NIAID.
The person’s mouth would start itching, and the person wouldn’t be able to eat the melon. The crossreaction happens frequently with cantaloupes. The
condition is known as oral allergy syndrome.

Diagnosis
Food allergies are diagnosed by first determining whether a person has an allergy or if symptoms
are related to a condition like food intolerance.
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Food allergies



Food allergies

The medical professional may be a board-certified
allergist, a doctor with education and experience in
treating allergies. However, some health plans may
require that the patient first see a family practice
doctor.
If food allergies are suspected, the doctor will take
a detailed case history. The doctor asks the patient if
there is a family history of allergies. Other questions
are related to the patient’s adverse reactions.
The doctor’s questions include how the food was
prepared, the amount eaten and what time the reaction happened. The patient describes the symptoms
and actions taken to relieve them. The doctor also
asks if the patient had other similar experiences when
eating that food.
The patient receives a physical exam. In addition,
the doctor may ask the patient to keep a food diary, a
log of what the person eats for one to two weeks. The
medical history and the food diary are used in conjunction with testing to diagnose the patient.
Allergy tests
Doctors generally start the testing process with a
skin test or a blood test. The prick skin test, which is
also known as the scratch test, examines the patient’s
reaction to a solution containing a protein that triggers allergies.
The doctor places a drop of the substance on the
patient’s arm or back. The doctor then uses a needle to
prick or scratch the skin. This allows the potential
allergen to enter the patient’s skin. If more than one
food allergy is suspected, the test is repeated with other
proteins applied to the skin. After about 15 minutes,
the doctor can read the reactions on the patient’s skin.
If there is no reaction, the patient is probably not
allergic to that food. The possibility of an allergy is
indicated by the presence of a wheal, a bump that
resembles a mosquito bite. The wheal signifies a positive reaction to the test. However, the test may show a
false positive, which is a reaction to a food that does
not cause allergies.
The skin test is not appropriate for people who are
severely allergic or have skin conditions like eczema.
Those people are given the RAST (radioallergosorbent test). This test measures the presence of foodspecific IgE in the blood. After a sample of the
patient’s blood is taken, it is sent to a laboratory.
The sample is tested with different foods. Levels of
antibodies are measured, and the reactions to different
proteins are ranked. While measurement systems may
vary, a high ranking indicates a high number of
1506

antibodies. Lab results are generally completed within
a week.
Results to this test may not be conclusive. A negative test may not have identified antibodies in the
patient’s blood. Positive results make it probable but
not definite that the patient has allergies.
Costs for blood and skin tests will vary, with fees
ranging from $10 to more than $300. Insurance may
cover some of the cost. While both tests are reliable,
they aren’t 100% accurate. If questions remain, the
diagnosis takes into account the patient’s medical history and the food diary. If necessary, the patient is put
on a special diet.
Elimination diet
If the skin or blood test shows strong positive
results, the doctor may put the patient on an elimination diet. This is done when needed to narrow the list
of suspected allergens. The person stops eating the
foods suspected of causing the allergic reaction. That
food is eliminated from the diet for from two to four
weeks. If allergy symptoms improve, the food is probably an allergen.
If more confirmation is needed, the doctor may
ask the patient to start eating the food again. The
elimination diet procedure is generally not utilized if
the patient initially had a severe reaction.
Food challenges
Other tests called food challenges may be performed. The challenges are done in a medical setting,
with a doctor present. The patient is given capsules
that each contain a different food. Some capsules
contain allergy-producing foods. Other capsules may
be placebos that won’t produce a reaction.
The patient swallows the capsule, and the doctor
watches for an allergic reaction. In an open food challenge, doctor and patient are aware of the capsule
contents. In a single-blind food challenge, only the
doctor knows. In a double-blind challenge, neither
doctor nor patient knows the contents.
Challenges are rarely authorized by health care
providers. Testing is time-consuming and many allergens are difficult to evaluate with the challenges,
according to NIAID.

Treatment
The treatment for food allergies is to avoid eating
the food that causes the allergy. This preventive treatment includes reading food labels. Manufacturers are
GALE ENCYCLOPEDIA OF MEDICINE

When reading food labels, people with food allergies should know that:


Words indicating the presence of milk include lactose, ghee, and whey.



Words signifying eggs in a product include albumin,
globulin, and ovomucin.



While it is apparent that peanuts are an ingredient in
a product like peanut butter, there could be peanuts
in hydrolyzed plant protein and hydrolyzed vegetable protein.



People with tree nut allergies should carefully read
the labels of products such as cereals and barbecue
sauce.



The American Dietetic Association cautions that
surimi, an ingredient in imitation seafood, is made
from fish muscle. Furthermore, fish in the form of
anchovies is sometimes an ingredient in Worcestshire
sauce.



Words on labels that signal the presence of wheat
include gluten, sietan, and vital gluten.
Allergies and children

Parents of children with food allergies need to
monitor their children’s food choices. They also must
know how to care for the child if there is an allergic
reaction. Parents need to notify the child’s school
about the condition. Caregivers should be informed,
too. Both the school and caregivers should know how
to handle an allergic reaction. Care must be taken
because a highly allergic person could react to a piece
of food as small as 1/44,000 of a peanut kernel, according to NIAID.

which is adrenaline. This is a prescription medication
sold commercially as the EpiPen auto injector. While
prices vary, one syringe costs about $50.
The person with allergies must know how to inject
the epinephrine. It is helpful for other family members
to know how to do this, and parents of an allergic child
must be trained in the procedure.
The person is injected at the first sign of a severe
reaction. Medical attention is required, and the person
should be taken to an emergency room. The person will
be treated and monitored because there could be a second severe reaction about four hours after the initial one.
Allergy treatment research
There was no cure for food allergies as of the spring
of 2005. That could change, with some relief available
for people diagnosed with peanut allergies. According
to a study reported on in 2003 in the New England
Journal of Medicine, 84 people who took the drug
TNX-901 had a decrease in their IgE antibody levels.
Organizations including the Food Allergy &
Anaphylaxis Network (FAAN) lauded the results of
the study that was conducted from July of 1999
through March of 2002. Work on that study was
stopped in 2004 when biotechnology companies
Genentech, Novartis, and Tanox concentrated efforts
instead on use of an asthma medication for treating
peanut allergies. Research started in June of 2004 on
omalizumab, a medication sold commercially as
Xolair. The study of Xolair’s effectiveness was
expected to take from two to three years.

Alternative treatment
The only treatment for food allergies is for a person to stop eating the food that causes the allergies.
Some alternative treatments may be helpful in easing
the symptoms caused by allergies. However, people
should check with their health care providers before
embarking on an alternative treatment.

Prognosis

Living with severe allergies
Despite precautions, people may accidentally eat
something that causes an allergic reaction. People with
severe allergies must be prepared to treat the condition
and prevent an anaphylactic reaction. A medical alert
bracelet should be worn. This informs people that the
person has a food allergy and could have severe
reactions.

Food allergies cannot be cured, but they can be
managed. The allergen-inducing foods should be
avoided. These foods should be replaced with others
that provide the vitamins and nutrients needed for a
healthy diet. Organizations including the American
Dietetic Association recommend the following dietetic
changes:

To reduce the risks from an anaphylactic reaction,
the person carries a syringe filled with epinephrine,



GALE ENCYCLOPEDIA OF MEDICINE

Milk is a source of calcium and vitamins A and D.
For people with milk allergies, alternate choices of
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Food allergies

required by the U.S. Food and Drug Administration
to list a product’s ingredients on the label. However, if
there is a question about an ingredient, the person
should contact the manufacturer before eating the
food. When dining out, people should ask if food
contains the allergen or ingredients contain the
allergy-inducing foods.

Food poisoning

calcium include calcium-fortified orange juice and
cereal.


Since eggs are an ingredient in products like bread,
egg-free sources of grains are an alternate source of
vitamin B.



Peanuts are a source of vitamin E, niacin, and magnesium. Other sources of these nutrients include
other legumes, meat, and grains.



Fish is a source of protein and nutrients like B vitamins and niacin. Alternate sources of these nutrients
should be sought.



Wheat is a source of many nutrients including niacin
and riboflavin. The person allergic to wheat should
substitute products made from grains such as oat,
corn, rice and barley.



Although soybeans are rich in nutrients, very little
soy is used in commercial products. As a result, a
person with this food allergy would not need to find a
safe substitute in order to get needed nutrients.

American Academy of Allergy, Asthma & Immunology. 555
East Wells Street Suite 1100, Milwaukee, WI 532023823. 414-272-6071. <http://www.aaaai.org>.
The Food Allergy & Anaphylaxis Network. 11781 Lee
Jackson Highway, Suite 160, Fairfax, VA 22033.
800-929-4040. <http://www.foodallergy.org>.
National Institute of Allergy and Infectious Diseases. 6610
Rockledge Drive, MSC 6612, Bethesda, MD 208926612. 301-496-5717. <http://www.niaid.nih.gov>.
OTHER

Food Allergy An Overview. National Institute of Allergy
and Infectious Diseases. July 2004. [cited March 30,
2005]. <http://www.niaid.nih.gov/publications/pdf/
foodallergy.pdf>.
Peanut Anti-IgE Study Update. The Food Allergy &
Anaphylaxis Network. September 2, 2004 [cited
April 5]. <http://www.foodallergy.org/Research/
antiigetherapy.html>.

Liz Swain

Prevention
People prevent the return of food allergies by following treatment guidelines. These include avoiding the
foods that cause allergic reactions, reading food labels,
and taking measures to prevent an anaphylactic reaction.
Anaphylaxis is a major concern after a diagnosis of
severe food allergies. To reduce the risks associated this
reaction, people with food allergies should wear medical
alert bracelets and never go anywhere without epinephrine. If possible, family members or friends of adults
with allergies should learn how to administer this
medication.
The American Dietetic Association advises people
to develop an emergency plan. ADA recommendations include preparing a list of the foods the person
is allergic to, three emergency contacts, the doctor’s
name, and a description of how to treat the reaction.
This list is kept with the epinephrine syringe.
Resources
BOOKS

Freund, Lee and Rejaunier, Jeanne. The Complete Idiot’s
Guide to Food Allergies. Penguin Group, USA, 2003.
The American Dietetic Association. Food Allergies: How to
Eat Safely and Enjoyably. John Wiley & Sons., 1998.
PERIODICALS
ORGANIZATIONS

American Dietetic Association. 120 South Riverside Plaza,
Suite 2000. Chicago, IL 60606-6995. 800-877-1600.
<http://www.eatright.org>.
1508

Food poisoning
Definition
Food poisoning is a general term for health problems arising from eating contaminated food. Food
may be contaminated by bacteria, viruses, environmental toxins, or toxins present within the food itself,
such as the poisons in some mushrooms or certain
seafood. Symptoms of food poisoning usually involve
nausea, vomiting and/or diarrhea. Some food-borne
toxins can affect the nervous system.

Description
Every year millions of people suffer from bouts of
vomiting and diarrhea each year that they blame on
‘‘something I ate.’’ These people are generally correct.
Each year in the United States, one to two bouts of
diarrheal illness occur in every adult. The Centers for
Disease Control and Prevention (CDC) estimates that
there are from six to 33 million cases of food poisoning
in the United States annually. Many cases are mild
and pass so rapidly that they are never diagnosed.
Occasionally a severe outbreak creates a newsworthy
public health hazard.
Classical food poisoning, sometimes incorrectly
called ptomaine poisoning, is caused by a variety of
different bacteria. The most common are Salmonella,
Staphylococcus aureus, Escherichia coli O157:H7 or
GALE ENCYCLOPEDIA OF MEDICINE

school for four years because she could not afford to pay
college tuition. Following her time as a teacher, Evans
enrolled at the Cornell University College of Agriculture,
earning her B.S. degree. Evans’ professor recommended
her for a scholarship, which she received, and she began
her master’s degree program at the University of Wisconsin
where she earned her degree in 1910.

(Corbis. Reproduced by permission.)

Alice Catherine Evans was born on January 29, 1881, in
Neath, Pennsylvania. Evans was the second of two children
born to Anne Evans and William Howell. Evans taught grade

other E. coli strains, Shigella, and Clostridium botulinum. Each has a slightly different incubation period
and duration, but all except C. botulinum cause inflammation of the intestines and diarrhea. Sometimes food
poisoning is called bacterial gastroenteritis or infectious diarrhea. Food and water can also be contaminated by viruses (such as the Norwalk agent that
causes diarrhea and the viruses of hepatitis A and E),
environmental toxins (heavy metals), and poisons produced within the food itself (mushroom poisoning or
fish and shellfish poisoning).

In 1911, Evans took a position with the University of
Wisconsin’s Dairy Division as a researcher studying
cheese-making instead of continuing her education. In
1913, she moved to Washington, D.C., with the division
and worked with a team on identifying the cause of contamination in raw cow’s milk. By 1917, Evans’ research
had shown that the bacteria responsible for undulant
(Malta) fever was very similar to one found when a cow
experienced a spontaneous abortion. When administered
to guinea pigs, the two bacteria produced similar results.
Her findings were met with much skepticism but, as time
went on, Evans’ research began to gain support. She continued to document cases of the disease and to argue for
the pasteurization process. Finally, after 1930, officials
responsible for public health and safety realized the
need for this process, which ultimately became a standard
procedure. Evans retired from her position with the
National Institute of Health in 1945 and died on
September 5, 1975.

of raw poultry sold at retail carry some diseasecausing bacteria. Other raw meat products and eggs
are contaminated to a lesser degree. Thorough cooking kills the bacteria and makes the food harmless.
However, properly cooked food can become recontaminated if it comes in contact with plates, cutting
boards, countertops, or utensils that were used with
raw meat and not cleaned and sanitized.

Careless food handling during the trip from farm
to table creates conditions for the growth of bacteria
that make people sick. Vegetables that are eaten raw,
such as lettuce, may be contaminated by bacteria in
soil, water, and dust during washing and packing.
Home canned and commercially canned food may be
improperly processed at too low a temperature or for
too short a time to kill the bacteria.

Cooked foods can also be contaminated after
cooking by bacteria carried by food handlers or from
bacteria in the environment. It is estimated that 50%
of healthy people have the bacteria Staphylococcus
aureus in their nasal passages and throat, and on
their skin and hair. Rubbing a runny nose, then touching food can introduce the bacteria into cooked food.
Bacteria flourish at room temperature, and will
rapidly grow into quantities capable of making people
sick. To prevent this growth, food must be kept hot or
cold, but never just warm.

Raw meats carry many food-borne bacterial
diseases. The United States Food and Drug
Administration (FDA) estimates that 60% or more

Although the food supply in the United States is
probably the safest in the world, anyone can get food
poisoning. Serious outbreaks are rare. When they

GALE ENCYCLOPEDIA OF MEDICINE

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Food poisoning

A L I C E C A T H E R I N E E V A N S (1881–1975)

Food poisoning

Common Pathogens Causing Food Poisoning

Pathogen

Common Host(s)

Campylobacter
E.coli 0157:H7
Listeria

Poultry
Undercooked, contaminated ground beef
Found in a variety of raw foods, such as uncooked
meats and vegetables, and in processed foods that
become contaminated after processing
Poultry, eggs, meat, and milk
This bacteria is transmitted through direct contact with
an infected person or from food or water that become
contaminated by an infected person
Contaminated seafood

Salmonella
Shigella

Vibrio

occur, the very young, the very old, and those with
immune system weaknesses have the most severe and
life-threatening cases. For example, this group is
20 times more likely to become infected with the
Salmonella bacteria than the general population.
Travel outside the United States to countries
where less attention is paid to sanitation, water purification, and good food handling practices increases the
chances that a person will get food poisoning. People
living in institutions such as nursing homes are also
more likely to get food poisoning.

Causes and symptoms
The symptoms of food poisoning occur because
food-borne bacteria release toxins or poisons as a
byproduct of their growth in the body. These toxins
(except those from C. botulinum) cause inflammation
and swelling of the stomach, small intestine and/or
large intestine. The result is abdominal muscle cramping, vomiting, diarrhea, fever, and the chance of dehydration. The severity of symptoms depends on the type
of bacteria, the amount consumed, and the individual’s general health and sensitivity to the bacterial
toxin.
Salmonella
According to a 2001 report from the CDC,
Salmonella caused almost 50,000 culture-confirmed
cases of food poisoning in the United States annually.
However, between two and four million probably
occur each year. Salmonella is found in egg yolks
from infected chickens, in raw and undercooked poultry and in other meats, dairy products, fish, shrimp,
and many more foods. The CDC estimates that one
out of every 50 consumers is exposed to a contaminated egg yolk each year. However, thorough cooking
1510

kills the bacteria and makes the food harmless.
Salmonella is also found in the feces of pet reptiles
such as turtles, lizards, and snakes.
About one out of every 1,000 people get food
poisoning from Salmonella. Of these, two-thirds are
under age 20, with the majority under age nine. Most
cases occur in the warm months between July and
October.
Symptoms of food poisoning begin eight to
72 hours after eating food contaminated with
Salmonella. These include traditional food poisoning
symptoms of abdominal pain, diarrhea, vomiting, and
fever. The symptoms generally last one to five days.
Dehydration can be a complication in severe cases.
People generally recover without antibiotic treatment,
although they may feel tired for a week after the active
symptoms subside.
Staphylococcus aureus
Staphylococcus aureus is found on humans and in
the environment in dust, air, and sewage. The bacteria
is spread primarily by food handlers using poor sanitary practices. Almost any food can be contaminated,
but salad dressings, milk products, cream pastries, and
any food kept at room temperature, rather than hot or
cold are likely candidates.
It is difficult to estimate the number of cases of
food poisoning from Staphylococcus aureus that occur
each year, because its symptoms are so similar to those
caused by other foodborne bacteria. Many cases are
mild and the victim never sees a doctor.
Symptoms appear rapidly, usually one to six
hours after the contaminated food is eaten. The
acute symptoms of vomiting and severe abdominal
cramps without fever usually last only three to six
hours and rarely more than 24 hours. Most people
recover without medical assistance. Deaths are rare.
Escherichia coli (E. coli)
There are many strains of E. coli, and not all of
them are harmful. The strain that causes most severe
food poisoning is E. coli O157:H7. Food poisoning by
E. coli occurs in three out of every 10,000 people.
Foodborne E. coli is found and transmitted mainly in
food derived from cows such as raw milk, raw or rare
ground beef and fruit or vegetables that are
contaminated.
Symptoms of food poisoning from E. coli are
slower to appear than those caused by some of the
other foodborne bacteria. E. coli produces toxins in
the large intestine rather than higher up in the
GALE ENCYCLOPEDIA OF MEDICINE

One to three days after eating contaminated food,
the victim with E. coli O157:H7 begins to have severe
abdominal cramps and watery diarrhea that usually
becomes bloody within 24 hours. There is little or no
fever, and rarely does the victim vomit. The bloody,
watery diarrhea lasts from one to eight days in uncomplicated cases.
Campylobacter jejuni (C. jejuni)
According to the FDA, C. jejuni is the leading
cause of bacterial diarrhea in the United States. It is
responsible for more cases of bacterial diarrhea than
Shigella and Salmonella combined. Anyone can get
food poisoning from C. jejuni, but children under
five and young adults between the ages of 15 and 29
are more frequently infected.
C. jejuni is carried by healthy cattle, chickens,
birds, and flies. It is not carried by healthy people in
the United States or Europe. The bacteria is also
found ponds and stream water. The ingestion of only
a few hundred C. jejuni bacteria can make a person
sick.
Symptoms of food poisoning begin two to five
days after eating food contaminated with C. jejuni.
These symptoms include fever, abdominal pain, nausea, headache, muscle pain, and diarrhea. The diarrhea can be watery or sticky and may contain blood.
Symptoms last from seven to 10 days, and relapses
occur in about one quarter of people who are infected.
Dehydration is a common complication. Other complications such as arthritis-like joint pain and hemolytic-uremic syndrome (HUS) are rare.
Shigella
Shigella is a common cause of diarrhea in travelers
to developing countries. It is associated with contaminated food and water, crowded living conditions, and
poor sanitation. The bacterial toxins affect the small
intestine.
Symptoms of food poisoning by Shigella appear
36–72 hours after eating contaminated food. These
symptoms are slightly different from those associated
with most foodborne bacteria. In addition to the
familiar watery diarrhea, nausea, vomiting, abdominal cramps, chills and fever occur. The diarrhea may
be quite severe with cramps progressing to classical
dysentery. Up to 40% of children with severe infections show neurological symptoms. These include
GALE ENCYCLOPEDIA OF MEDICINE

seizures caused by fever, confusion, headache,
lethargy, and a stiff neck that resembles meningitis.
The disease runs its course usually in two to three
days but may last longer. Dehydration is a common
complication. Most people recover on their own,
although they may feel exhausted, but children who
are malnourished or have weakened immune systems
may die.
Clostridium botulinum (C. botulinum)
C. botulinum, which causes both adult botulism
and infant botulism, is unlike any of the other foodborne bacteria. First, C. botulinum is an anaerobic
bacterium in that it can only live in the absence of
oxygen. Second, the toxins from C. botulinum are
neurotoxins. They poison the nervous system, causing
paralysis without the vomiting and diarrhea associated with other foodborne illnesses. Third, toxins
that cause adult botulism are released when the bacteria grows in an airless environment outside the body.
They can be broken down and made harmless by heat.
Finally, botulism is much more likely to be fatal even
in tiny quantities.
Adult botulism outbreaks are usually associated
with home canned food, although occasionally commercially canned or vacuum packed foods are responsible
for the disease. C. botulinum grows well in
non-acidic, oxygen-free environments. If food is canned
at too low heat or for too brief a time, the bacteria is not
killed. It reproduces inside the can or jar, releasing its
deadly neurotoxin. The toxin can be made harmless by
heating the contaminated food to boiling for ten minutes. However, even a very small amount of the
C. botulinum toxin can cause serious illness or death.
Symptoms of adult botulism appear about 18–36
hours after the contaminated food is eaten, although
there are documented times of onset ranging from four
hours to eight days. Initially a person suffering from
botulism feels weakness and dizziness followed by
double vision. Symptoms progress to difficulty speaking and swallowing. Paralysis moves down the body,
and when the respiratory muscles are paralyzed, death
results from asphyxiation. People who show any signs
of botulism poisoning must receive immediate emergency medical care to increase their chance of survival.
Infant botulism is a form of botulism first recognized in 1976. It differs from food-borne botulism in
its causes and symptoms. Infant botulism occurs when
a child under the age of one year ingests the spores of
C. botulinum. These spores are found in soil, but a
more common source of spores is honey.
1511

Food poisoning

digestive system. This accounts for the delay in symptoms and the fact that vomiting rarely occurs in E. coli
food poisoning.

Food poisoning

The C. botulinum spores lodge in the baby’s intestinal tract and begin to grow, producing their neurotoxin. Onset of symptoms is gradual. Initially the baby
is constipated. This is followed by poor feeding,
lethargy, weakness, drooling, and a distinctive wailing
cry. Eventually, the baby loses the ability to control its
head muscles. From there the paralysis progresses to
the rest of the body.

Diagnosis
One important aspect of diagnosing food poisoning is for doctors to determine if a number of people
have eaten the same food and show the same symptoms of illness. When this happens, food poisoning is
strongly suspected. The diagnosis is confirmed when
the suspected bacteria is found in a stool culture or a
fecal smear from the person. Other laboratory tests are
used to isolate bacteria from a sample of the contaminated food. Botulism is usually diagnosed from its
distinctive neurological symptoms, since rapid treatment is essential. Many cases of food poisoning go
undiagnosed, since a definite diagnosis is not necessary to effectively treat the symptoms. Because it takes
time for symptoms to develop, it is not necessarily the
most recent food one has eaten that is the cause of the
symptoms.

liquids frequently but in small quantities. Once active
symptoms stop, they should eat bland, soft, easy to
digest foods for two to three days. One example is the
BRAT diet of bananas, rice, applesauce, and toast, all
of which are easy to digest. Milk products, spicy food,
alcohol and fresh fruit should be avoided for a few
days, although babies should continue to breastfeed.
These modifications are often all the treatment that is
necessary.
Severe bacterial food poisonings are sometimes
treated with antibiotics. Trimethoprim and sulfamethoxazole (Septra, Bactrim), ampicillin (Amcill,
Polycill) or ciprofloxacin (Ciloxan, Cipro) are most
frequently used.
Botulism is treated in a different way from other
bacterial food poisonings. Botulism antitoxin is given
to adults, but not infants, if it can be administered
within 72 hours after symptoms are first observed. If
given later, it provides no benefit.
Both infants and adults require hospitalization,
often in the intensive care unit. If the ability to breathe
is impaired, patients are put on a mechanical ventilator to assist their breathing and are fed intravenously
until the paralysis passes.

Alternative treatment
Treatment
Treatment of food poisoning, except that caused
by C. botulinum, focuses on preventing dehydration by
replacing fluids and electrolytes lost through vomiting
and diarrhea. Electrolytes are salts and minerals that
form electrically charges particles (ions) in body fluids.
Electrolytes are important because they control body
fluid balance and are important for all major body
reactions. Pharmacists can recommend effective, pleasant-tasting, electrolytically balanced replacement
fluids that are available without a prescription.
When more fluids are being lost than can be consumed, dehydration may occur. Dehydration more
likely to happen in the very young, the elderly, and
people who are taking diuretics. To prevent dehydration, a doctor may give fluids intravenously.
In very serious cases of food poisoning, medications may be given to stop abdominal cramping and
vomiting. Anti-diarrheal medications are not usually
given. Stopping the diarrhea keeps the toxins in the
body longer and may prolong the infection.
People with food poisoning should modify their
diet. During period of active vomiting and diarrhea
they should not try to eat and should drink only clear
1512

Alternative practitioners offer the same advice as
traditional practitioners concerning diet modification.
In addition they recommend taking charcoal tablets,
Lactobacillus acidophilus, Lactobacillus bulgaricus,
and citrus seed extract. An electrolyte replacement
fluid can be made at home by adding one teaspoon
of salt and four teaspoons of sugar to one quart of
water. For food poisoning other than botulism, two
homeopathic remedies, either Arsenicum album or
Nux vomica, are strongly recommended.

Prognosis
Most cases of food poisoning (except botulism)
clear up on their own within one week without medical
assistance. The ill person may continue feel tired for a
few days after active symptoms stop. So long as the ill
person does not become dehydrated, there are few
complications. Deaths are rare and usually occur in
the very young, the very old and people whose immune
systems are already weakened.
Complications of Salmonella food poisoning
include arthritis-like symptoms that occur three to
four weeks after infection. Although deaths from
Salmonella are rare, they do occur. Most deaths
GALE ENCYCLOPEDIA OF MEDICINE

throw away bulging or leaking cans or any food that
smells spoiled

Diuretic—Medication that increases the urine output of the body.
Electrolytes—Salts and minerals that produce electrically charged particles (ions) in body fluids.
Common human electrolytes are sodium chloride,
potassium, calcium, and sodium bicarbonate.
Electrolytes control the fluid balance of the body
and are important in muscle contraction, energy
generation, and almost all major biochemical reactions in the body.
Lactobacillus acidophilus—This bacteria is
found in yogurt and changes the balance of the
bacteria in the intestine in a beneficial way.
Platelets—Blood cells that help the blood to clot.



wash hands well before and during food preparation
and after using the bathroom



sanitize food preparation surfaces regularly

caused by Salmonella food poisoning have occurred in
elderly people in nursing homes.
Adults usually recover without medical intervention, but many children need to be hospitalized as the
result of E. coli food poisoning. E. coli toxins may be
absorbed into the blood stream where they destroy red
blood cells and platelets. Platelets are important in
blood clotting. About 5% of victims develop hemolytic-uremic syndrome which results in sudden kidney
failure and makes dialysis necessary. (Dialysis is a
medical procedure used to filter the body’s waste product when the kidneys have failed).
Botulism is the deadliest of the bacterial foodborne illnesses. With prompt medical care, the death
rate is less than 10%.

Prevention
Food poisoning is almost entirely preventable by
practicing good sanitation and good food handling
techniques. These include:


keep hot foods hot and cold foods cold



cook meat to the recommended internal temperature, use a meat thermometer to check and cook
eggs until they are no longer runny



refrigerate leftovers promptly, do not let food stand
at room temperature



avoid contaminating surfaces and other foods with
the juices of uncooked meats



wash fruits and vegetables before using



purchase pasteurized dairy products and fruit juices

GALE ENCYCLOPEDIA OF MEDICINE

Resources
OTHER

U. S. Food and Drug Administration. Center for Food
Safety and Applied Nutrition. Bad Bug Book. <http://
vm.cfsan.fda.gov>.

Suzanne M. Lutwick, MPH

Foot acupressure see Reflexology

Foot care
Definition
Foot care involves all aspects of preventative and
corrective care of the foot and ankle. Doctors specializing in foot care are called podiatrists.

Purpose
During an average lifetime, each person walks
about 115,000 miles and three-quarters of people
have foot problems at some point in their lives.
Foot problems can arise from wearing ill-fitting
shoes, from general wear and tear, as a result of injury,
or as a complication of disease. People with diabetes
mellitus or circulatory diseases are 20 times more likely
to have foot problems than the general public.
Podiatrists are doctors who specialize in treating the
foot and ankle. Other doctors who have experience with
foot problems are family physicians, orthopedists, sports
medicine specialists, and those who care for diabetics.
Problems with the feet include foot pain, joint inflammation, plantar warts, fungal infections (like athlete’s foot),
nerve disorders, torn ligaments, broken bones, bacterial
infections, and tissue injuries (like frostbite).

Precautions
People with diabetes or circulatory disorders
should be alert to even small foot problems. In these
people, a break in the skin can lead to infection, gangrene, and amputation.
1513

Foot care



KEY TERMS

Foreign objects

Description
Daily foot care for people likely to develop foot
problems includes washing the feet in tepid water with
mild soap and oiling the feet with vegetable oil or a
lanolin-based lotion. Toenails should be cut straight
across above the level of the skin after soaking the feet
in tepid water. Corns and calluses should not be cut. If
they need removal, it should be done under the care of a
doctor. Athletes foot and plantar warts should also be
treated by a doctor if they develop in high risk patients.
Many people with diabetes or circulatory disorders have problems with cold feet. These problems can
be reduced by avoiding smoking tobacco (smoking
constricts the blood vessels), wearing warm socks,
not crossing the legs while sitting or not sitting in one
position too long, or avoiding constricting stockings.
People with circulatory problems should not use
heating pads or hot water bottles on their feet, as even
moderate heat can damage the skin if circulation is
impaired.

Preparation
No special preparation other than an understanding of the nature of foot problems is necessary to begin
routine foot care.

Aftercare
Foot care is preventative and should be ongoing
throughout a person’s life.

Risks

Definition
‘‘Foreign’’ means ‘‘originating elsewhere’’ or simply ‘‘outside the body.’’ Foreign bodies typically
become lodged in the eyes, ears, nose, airways, and
rectum of human beings.

Description
Both children and adults experience problems
caused by foreign objects getting stuck in their bodies.
Young children, in particular, are naturally curious
and may intentionally put shiny objects, such as
coins or button batteries, into their mouths. They
also like to stick things in their ears and up their
noses. Adults may accidentally swallow a non-food
object or inhale a foreign body that gets stuck in the
throat. Even if an object like a toothpick successfully
passes through the esophagus and into the stomach, it
can get stuck inside the rectum. Airborne particles can
lodge in the eyes of people at any age.
Foreign bodies can be in hollow organs (like swallowed batteries) or in tissues (like bullets). They can be
inert or irritating. If they irritate they will cause
inflammation and scarring. They can bring infection
with them or acquire it and protect it from the body’s
immune defenses. They can obstruct passageways
either by their size or by the scarring they cause.
Some can be toxic.

Causes and symptoms

There are no risks associated with foot care. The
risks are in ignoring the feet and allowing problems to
develop.

Normal results
With regular care, foot disorders such as infections, skin ulcers, and gangrene can be prevented.
Resources
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.
American Podiatry Association. 20 Chevy Chase Circle,
NW, Washington, D.C. 20015.

Tish Davidson, A.M.

Foreign bodies see Foreign objects
1514

Foreign objects

Eyes
Dust, dirt, sand, or other airborne material can
lodge in the eyes, causing minor irritation and redness.
More serious damage can be caused by hard or sharp
objects that penetrate the surface and become
embedded in the cornea or conjunctiva (the mucous
membranes around the inner surface of the eyelids).
Swelling, redness, bleeding from the surface blood
vessels, sensitivity to light, and sudden vision problems are all symptoms of foreign matter in the eyes.
Ears and nose
Children will sometimes put things into their
noses, ears, and other openings. Beans, popcorn kernels, raisins, and beads are just a few of the many items
that have been found in these bodily cavities. On
occasion, insects may also fly into the ears and nose.
Pain, hearing loss, and a sense of something stuck in
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis

X ray of swallowed spoon and blade in the intestine. (Photo
Researchers. Reproduced by permission.)

the ear are symptoms of foreign bodies in the ears. A
smelly, bloody discharge from one nostril is a symptom of foreign bodies in the nose.

The symptoms are as diverse as the objects and
their locations. The most common manifestation of a
foreign object anywhere in the body is infection. Even
if the object started out sterile, germs still seem to find
it and are able to hide from the body’s defenses there.
Blockage of passageways–breathing, digestive or
excretory–is another result. Pain is common.

Treatment
Eyes

At a certain age children will eat anything. A very
partial list of items recovered from young stomachs
includes the following: Coins, chicken bones, fish
bones, beads, rocks, plastic toys, pins, keys, round
stones, marbles, nails, rings, batteries, ball bearings,
screws, staples, washers, a heart pendant, a clothespin
spring, and a toy soldier. Some of these items will pass
right on through and come out the other end. The
progress of metal objects has been successfully followed with a metal detector. Others, like sharp
bones, can get stuck and cause trouble. Batteries are
corrosive and must be removed immediately.

Small particles like sand may be removable without medical help, but if the object is not visible or
cannot be retrieved, prompt emergency treatment is
necessary. Trauma to the eyes can lead to loss of vision
and should never be ignored. Before attempting any
treatment, the person should move to a well-lighted
area where the object can be more easily spotted.
Hands should be washed and only clean, preferably
sterile, materials should make contact with the eyes. If
the particle is small, it can be dislodged by blinking or
pulling the upper lid over the lower lid and flushing
out the speck. A clean cloth can also be used to
pick out the offending particle. Afterwards, the eye
should be rinsed with clean, lukewarm water or an
opthalmic wash.

Children eat things and stick things into their
bodily openings of their own volition. But they inhale
them unwittingly. The most commonly inhaled item is
probably a peanut. A crayon and a cockroach have
been found in a child’s windpipes. These items always
cause symptoms (difficulty swallowing and spitting up
saliva, for instance) and may elude detection for some
time while the child is being treated for asthma or
recurring pneumonia.

If the foreign object cannot be removed at home,
the eye should be lightly covered with sterile gauze to
discourage rubbing. A physician will use a strong light
and possibly special eyedrops to locate the object.
Surgical tweezers can effectively remove many objects.
An antibiotic sterile ointment and a patch may be
prescribed. If the foreign body has penetrated the
deeper layers of the eye, an opthalmic surgeon will be
consulted for emergency treatment.

Airways and stomach

Adults are not exempt from unorthodox inedibles. Dental devices are commonly swallowed.
Adults with mental illness or subversive motives may
swallow inappropriate objects, such as toothbrushes.
Rectum
Sometimes a foreign object will successfully pass
throught the throat and stomach only to get stuck at
the juncture between the rectum and the anal canal.
GALE ENCYCLOPEDIA OF MEDICINE

Ears and nose
A number of ingenious extraction methods have
been devised for removing foreign objects from the
nose and ears. A bead in a nostril, for example, can
be popped out by blowing into the mouth while holding the other nostril closed. Skilled practitioners have
removed peas from the ears by tiny improvised corkscrews; marbles by q-tips with super glue. Tweezers
1515

Foreign objects

Items may also be self-introduced to enhance sexual
stimulation and then get stuck. Sudden sharp pain
during elimination may signify that an object is lodged
in the rectum. Other symptoms vary depending upon
the size of the object, its location, how long it has been
in place, and whether or not infection has set in.

Fracture repair

KEY TERMS
Bronchoscope—An illuminated instrument that is
inserted into the airway to inspect and retrieve
objects from the bronchial tubes.
Conjunctiva—Mucous membranes around the
inner surface of the eyelid.
Cornea—The rounded, transparent portion of the
eye that covers the pupil and iris and lets light into
the interior
Endoscopy—The surgical use of long, thin instruments that have both viewing and operating
capabilities.
Heimlich maneuver—An emergency procedure for
removing a foreign object lodged in the airway that
is preventing the person from breathing. To perform
the Heimlich maneuver on a conscious adult, the
rescuer stands behind the victim and encircles his
waist. The rescuer makes a fist with one hand and
places the other hand on top, positioned below the
rib cage and above the waist. The rescuer then
applies pressure by a series of upward and inward
thrusts to force the foreign object back up the
victim’s trachea.

irritating, sharp nor large may be followed as they
continue on through. Sterile objects that are causing
no symptoms may be left in place. Surgical removal of
the offending object is necessary if it is causing
symptoms.
Rectum
A rectal retractor can remove objects that a physician can feel during physical examination. Surgery
may be required for objects deeply lodged within the
recturm.

Prevention
Using common sense and following safety precautions are the best ways to prevent foreign objects from
entering the body. For instance, parents and grandparents should toddler-proof their homes, storing batteries in a locked cabinet and properly disposing of used
batteries, so they are not in a location where curious
preschoolers can fish them out of a wastebasket.
To minimize the chance of youngsters inhaling food,
parents should not allow children to eat while walking
or playing. Adults should chew food thoroughly and
not talk while chewing. Many eye injuries can be
prevented by wearing safety glasses while using tools
Resources

often work well, too. Insects can be floated out of the
ear by pouring warm (not hot) mineral oil, olive oil, or
baby oil into the ear canal. Items that are lodged deep
in the ear canal are more difficult to remove because of
the possibility of damaging the ear drum. These
require emergency treatment from a qualified
physician.
Airways and stomach
Mechanical obstruction of the airways, which
commonly occurs when food gets lodged in the throat,
can be treated by applying the Heimlich maneuver. If
the object is lodged lower in the airway, a bronchoscope (a special instrument to view the airway and
remove obstructions) can be inserted. On other occasions, as when the object is blocking the entrance to
the stomach, a fiberoptic endoscope (an illuminated
instrument that views the interior of a body cavity)
may be used. The physician typically administers a
sedative and anesthetizes the throat. The foreign
object will then either be pulled out or pushed into
the stomach, depending on whether or not the physician thinks it will pass through the digestive tract on its
own. Objects in the digestive tract that are neither
1516

PERIODICALS

Gilchrist, B. F., et al. ‘‘Pearls and Perils in the Management
of Prolonged, Peculiar, Penetrating Esophageal
Foreign Bodies in Children.’’ Journal of Pediatric
Surgery 32, no. 10 (October 1997): 1429-31.

J. Ricker Polsdorfer, MD

Fourn see Flesh-eating disease
47, XXY syndrome see Klinefelter syndrome

Fracture repair
Definition
Fracture repair is the process of rejoining and
realigning the ends of broken bones. This procedure
is usually performed by an orthopedist, general surgeon, or family doctor. In cases of an emergency, first
aid measures should be evoked for temporary realignment and immobilization until proper medical help is
available.
GALE ENCYCLOPEDIA OF MEDICINE

An x-ray image of a healing fracture. (Photograph by Bates,
M.D., Custom Medical Stock Photo. Reproduced by permission.)

Purpose
Fracture repair is required when there is a need for
restoration of the normal position and function of the
broken bone. Throughout the stages of fracture healing, the bones must be held firmly in the correct position. In the event the fracture is not properly repaired,
malalignment of the bone may occur, resulting in
possible physical dysfunction of the bone or joint of
that region of the body.

Precautions
Precautions for fracture repair are anything
found to be significant with patients’ medical diagnosis and history. This would include an individual’s tolerance to anesthesia and the presence of
bleeding disorders that may be present to complicate surgery.

Description
Fracture repair is applied by means of traction,
surgery, and/or by immobilization of the bones. The
bone fragments are aligned as close as possible to the
normal position without injuring the skin. Metal
wires or screws may be needed to align smaller bone
fragments. Once the broken ends of the bone are set,
the affected area is immobilized for several weeks
and kept rigid with a sling, plaster cast, brace or
splint. With the use of traction, muscle pull on the
fracture site is overcome by weights attached to a
series of ropes running over pulleys. Strategically
implanted electrical stimulation devices have proven
beneficial in healing a fracture site, especially when
the fracture is healing poorly and repair by other
means is difficult.
GALE ENCYCLOPEDIA OF MEDICINE

Emergency splinting may be required to immobilize the body part or parts involved. When fracture
repair is necessary, the procedure is often performed in
a hospital but can also be successfully done in an outpatient surgical facility, doctor’s office or emergency
room. Before any surgery for fracture repair, blood
and urine studies may be taken from the patient.
X rays may follow this if not previously acquired. It
has been noted however, that not all fractures are
immediately apparent on an initial x-ray examination.
In this case, where a fracture is definitely suspected the
extent of the fracture can be properly diagnosed by
repeating the x rays 10–14 days later. Depending upon
the situation, local or general anesthesia may be used
for fracture repair.

Aftercare
After surgery, x rays may be again taken through
the cast or splint to evaluate if rejoined pieces remain
in good position for healing. This is usually performed
either before the application of the splint or at least
before the patient is awakened from the general
anesthesia. The patient needs to be cautious not to
place excess pressure on any part of the cast until it is
completely dry. The patient also should avoid excess
pressure on the operative site until complete healing
has taken place and the injury has been re-examined
by the physician. If the cast becomes exposed to moisture it may soften and require repair. The patient
should also be instructed to keep the injured region
propped up whenever possible to reduce the possibility
of swelling.

Risks
Surgical risks of fracture repair are greater in
patients over 60 years of age because the bones often
taking longer to heal properly. Obesity may place
extra stress on the healing site, affecting healing and
possibly risking reinjury. Smoking may slow the healing process after fracture repair, as well as poor nutrition, alcoholism, and chronic illness. Some medications
may affect the fracture site, causing poor union. Such
medications include anti-hypertensives and cortisone.
Possible complications following fracture repair
include excessive bleeding, improper fit of joined
bone ends, pressure on nearby nerves, delayed healing,
and a permanent incomplete healing of the fracture. If
there is a poor blood supply to the fractured site with
one of the portions of broken bone not properly supplied by the blood, the bony portion will die and
1517

Fracture repair

Preparation

Fractures

KEY TERMS
Compound fracture—A fracture in which the
broken end or ends of the bone have torn through
the skin. Compound fractures are also known as
open fractures
Staphylococcal infection—An infection caused by
any of several pathogenic species of staphylococcus, commonly characterized by the formation of
abscesses of the skin or other organs.
Streptococcal infection—An infection caused by a
pathogenic bacteria of one of several species of the
genus streptococcus or their toxins. Almost any
organ in the body may be involved.

Improper alignment causing deformity is also an
abnormal outcome, however, with today’s medical
technology it is relatively rare.
Resources
OTHER

Griffith, H. Winter. ‘‘Fracture Repair.’’ThriveOnline. 1998.
[cited Mach 3, 1998]. <http://
thriveonline.oxygen.com>.

Jeffrey P. Larson, RPT

Fractures
healing of the fracture will not take place. This is called
aseptic necrosis. Poor immobilization of the fracture
from improper casting which permits motion between
the bone parts may prevent healing and repair of the
bone with possible deformity. Infection can interfere
with bone repair. This risk is greater in the case
of a compound fracture (a bone fracture causing an
open wound) where ideal conditions are present for
severe streptococcal and staphylococcal infections.
Occasionally, fractured bones in the elderly may
possibly never heal properly. The risk is increased
when nutrition is poor.

Normal results
Once the procedure for fracture repair is completed, the body begins to produce new tissue to bridge
the broken pieces. At first, this tissue (called a callus) is
soft and easily injured. Later, the body deposits bone
minerals until the callus becomes a solid piece of bone.
The fracture site is thus strengthened further with extra
bone. It usually takes about six weeks for a broken bone
to heal together. The exact time required for healing
depends on the type of fracture and the extent of
damage. Before the use of x rays, fracture repair was
not always accurate, resulting in crippling deformities.
With modern x-ray technology, the physician can view
the extent of the fracture, check the setting following the
repair, and be certain after the procedure that the bones
have not moved from their intended alignment.
Children’s bones usually heal relatively rapidly.

Abnormal results
Abnormal results of fracture repair include
damage to nearby nerves or primary blood vessels.
1518

Definition
A fracture is a complete or incomplete break in
a bone resulting from the application of excessive
force.

Description
A fracture usually results from traumatic injury to
bones causing the continuity of bone tissues or bony
cartilage to be disrupted or broken. Fracture classifications include simple, compound, incomplete and
complete. Simple fractures (more recently called
‘‘closed’’) are not obvious as the skin has not been
ruptured and remains intact. Compound fractures
(now commonly called ‘‘open’’) break the skin, exposing bone and causing additional soft tissue injury and
possible infection. A single fracture means that one
fracture only has occurred and multiple fractures refer
to more than one fracture occurring in the same bone.
Fractures are termed complete if the break is completely through the bone and described as incomplete or
‘‘greenstick’’ if the fracture occurs partly across a bone
shaft. This latter type of fracture is often the result of
bending or crushing forces applied to a bone.
Fractures are also named according to the specific
part of the bone involved and the nature of the break.
Identification of a fracture line can further classify
fractures. Types include linear, oblique, transverse,
longitudinal, and spiral fractures. Fractures can be
further subdivided by the positions of bony fragments
and are described as comminuted, non-displaced,
impacted, overriding, angulated, displaced, avulsed,
and segmental. Additionally, an injury may be classified as a fracture-dislocation when a fracture involves
the bony structures of any joint with associated
dislocation of the same joint.
GALE ENCYCLOPEDIA OF MEDICINE

Linear fractures have a break that runs parallel
to the bone’s main axis or in the direction of the
bone’s shaft. For example, a linear fracture of the
arm bone could extend the entire length of the bone.
Oblique and transverse fractures differ in that an
oblique fracture crosses a bone at approximately a
45 8 angle to the bone’s axis. In contrast, a transverse
fracture crosses a bone’s axis at a 90 8 angle. A longitudinal fracture is similar to a linear fracture. Its
fracture line extends along the shaft but is more
irregular in shape and does not run parallel to the
bone’s axis. Spiral fractures are described as crossing
a bone at an oblique angle, creating a spiral pattern.
This break usually occurs in the long bones of the
body such as the upper arm bone (humerus) or the
thigh bone (femur).
Bony fragment position identification
Comminuted fractures have two or more fragments broken into small pieces, in addition to the
upper and lower halves of a fractured bone.
Fragments of bone that maintain their normal
alignment following a fracture are described as
being non-displaced. An impacted fracture is characterized as a bone fragment forced into or onto
another fragment resulting from a compressive
force. Overriding is a term used to describe bony
fragments that overlap and shorten the total length
of a bone. Angulated fragments result in pieces of
bone being at angles to each other. A displaced
bony fragment occurs from disruption of normal
bone alignment with deformity of these segments
separate from one another. An avulsed fragment
occurs when bone fragments are pulled from their
normal position by forceful muscle contractions or
resistance from ligaments. Segmental fragmented
positioning occurs if fractures in two adjacent
areas occur, leaving an isolated central segment.
An example of segmental alignment is when the
arm bone fractures in two separate places, with
displacement of the middle section of bone.

Causes and symptoms
Individuals with high activity levels appear to be
at greater risk for fractures. This group includes children and athletes participating in contact sports.
Because of an increase in bone brittleness with aging,
elderly persons are also included in this high-risk
population. Up to the age of 50, more men suffer
from fractures than women due to occupational
hazards. However, after the age of 50, women are
GALE ENCYCLOPEDIA OF MEDICINE

more prone to fractures than men. Specific diseases
causing an increased risk for fractures include Paget’s
disease, rickets, osteogenesis imperfecta, osteoporosis,
bone cancer and tumors, and prolonged disuse of a
nonfunctional body part such as after a stroke.
Symptoms of fractures usually begin with pain
that increases with attempted movement or use of the
area and swelling at the involved site. The skin in the
area may be pale and an obvious deformity may be
present. In more severe cases, there may be a loss of
pulse below the fracture site, such as in the extremities,
accompanied by numbness, tingling, or paralysis below
the fracture. An open or compound fracture is often
accompanied by bleeding or bruising. If the lower
limbs or pelvis are fractured, pain and resistance to
movement usually accompany the injury causing difficulty with weight bearing.

Diagnosis
Diagnosis begins immediately with an individual’s own observation of symptoms. A thorough
medical history and physical exam by a physician
often reveals the presence of a fracture. An x ray of
the injured area is the most common test used to
determine the presence of a bone fracture. Any
x ray series performed involves at least two views of
the area to confirm the presence of the fracture
because not all fractures are apparent on a single
x ray. Some fractures are often difficult to see and
may require several views at different angles to see
clear fracture lines. In some cases, CT, MRI or other
imaging tests are required to demonstrate fracture.
Sometimes, especially with children, the initial x ray
may not show any fractures but repeat seven to
14 days later may show changes in the bone(s) of
the affected area. If a fracture is open and occurs in
conjunction with soft tissue injury, further laboratory studies are often conducted to determine if
blood loss has occurred.
In the event of exercise-related stress fractures
(micro-fractures due to excessive stress), a tuning
fork can provide a simple, inexpensive test. The
tuning fork is a metal instrument with a stem and
two prongs that vibrate when struck. If an individual has increased pain when the tuning fork is
placed on a bone, such as the tibia or shinbone,
the likelihood of a stress fracture is high. Bone
scans also are helpful in detecting stress fractures.
In this diagnostic procedure, a radioactive tracer is
injected into the bloodstream and images are taken
of specific areas or the entire skeleton by CT
or MRI.
1519

Fractures

Fractures line identification

Fractures

Greenstick

Compound

Pott's

Colles'

Fractures usually result from a traumatic injury to a bone where the continuity of bone tissues or bony cartilage is disrupted
or broken. The illustrations above feature common sites where fractures occur. (Illustration by Electronic Illustrators Group.)

Treatment

Fracture reduction

Treatment depends on the type of fracture, its
severity, the individual’s age and general health. The
first priority in treating any fracture is to address the
entire medical status of the patient. Medical personnel
are trained not allow a painful, deformed limb to
distract them from potentially life-threatening injury
elsewhere or shock. If an open fracture is accompanied
by serious soft tissue injury, it may be necessary to
control bleeding and the shock that can accompany
loss of blood.

Fracture reduction is the procedure by which a
fractured bone is realigned in normal position. It can
be either closed or open. Closed reduction refers to
realigning bones without breaking the skin. It is performed with manual manipulation and/or traction
and is commonly done with some kind of anesthetic.
Open reduction primarily refers to surgery that is
performed to realign bones or fragments. Fractures
with little or no displacement may not require any
form of reduction.

First aid is the appropriate initial treatment in
emergency situations. It includes proper splinting,
control of blood loss, and monitoring vital signs such
as breathing and circulation.

Traction is used to help reposition a broken
bone. It works by applying pressure to restore
proper alignment. The traction device immobilizes
the area and maintains realignment as the bone
heals. A fractured bone is immobilized by applying
opposing force at both ends of the injured area,
using an equal amount of traction and countertraction. Weights provide the traction pull needed
or the pull is achieved by positioning the individual’s body weight appropriately. Traction is a
form of closed reduction and is sometimes used
as an alternative to surgery. Since it restricts movement of the affected limb or body part, it may
confine a person to bed rest for an extended period
of time.

Immobilization
Immobilization of a fracture site can be done internally or externally. The primary goal of immobilization
is to maintain the realignment of a bone long enough
for healing to start and progress. Immobilization by
external fixation uses splints, casts, or braces. This
may be the primary and only procedure for fracture
treatment. Splinting to immobilize a fracture can be
done with or without traction. In emergency situations
if the injured individual must be moved by someone
other than a trained medical person, splinting is a useful
form of fracture management. It should be done without causing additional pain and without moving the
bone segments. In a clinical environment, plaster of
Paris casts are used for immobilization. Braces are useful as they often allow movement above and below a
fracture site. Treatments for stress fractures include rest
and decreasing or stopping any activity that causes or
increases pain.
1520

A person may need open reduction if there is
an open, severe, or comminuted fracture. This procedure allows a physician to examine and surgically
correct associated soft tissue damage while reducing the fracture and, if necessary, applying internal or external devices. Internal fixation involves
the use of metallic devices inserted into or through
bone to hold the fracture in a set position and
alignment while it heals. Devices include plates,
GALE ENCYCLOPEDIA OF MEDICINE

Avulsion fracture—A fracture caused by the tearing
away of a fragment of bone where a strong ligament
or tendon attachment forcibly pulls the fragment
away from the bone tissue.
Axis—A line that passes through the center of the
body or body part.
Comminuted fracture—A fracture where there are
several breaks in a bone creating numerous fragments.
Compartment syndrome—Compartment syndrome
is a condition in which a muscle swells but is constricted by the connective tissue around it, which cuts
off blood supply to the muscle.
Contrast hydrotherapy—A series of hot and cold
water applications. A hot compress (as hot as an
individual can tolerate) is applied for three minutes
followed by an ice cold compress for 30 seconds.
These applications are repeated three times each and
ending with the cold compress.
Osteogenesis imperfecta—A genetic disorder involving defective development of connective tissues,
characterized by brittle and fragile bones that are
easily fractured by the slightest trauma.
Osteoporosis—Literally meaning ‘‘porous bones,’’ this
condition occurs when bones lose an excessive amount
of their protein and mineral content, particularly

nails, screws, and rods. When healing is complete,
the surgeon may or may not remove these devices.
Virtually any hip fracture requires open reduction
and internal fixation so that the bone will be able
to support the patient’s weight.

Alternative treatment
In addition to the importance of calcium for strong
bones, many alternative treatment approaches recommend use of mineral supplements to help build and
maintain a healthy, resilient skeleton. Some physical
therapists use electro-stimulation over a fractured site
to promote and expedite healing. Chinese traditional
medicine may be helpful by working to reconnect chi
through the meridian lines along the line of a fracture.
Homeopathy can enhance the body’s healing process.
Two particularly useful homeopathic remedies are
Arnica (Arnica montana) and Symphytum (Symphytum
officinalis). If possible, applying contrast hydrotherapy
to an extremity (e.g., a hand or foot) of a fractured area
can assist healing by enhancing circulation.
GALE ENCYCLOPEDIA OF MEDICINE

calcium. Over time, bone mass and strength are
reduced leading to increased risk of fractures.
Paget’s disease—Chromic disorder of unknown cause,
usually affecting middle aged and elderly people, characterized by enlarged and deformed bones. Excessive
breakdown and formation of bone tissue occurs with
Paget’s disease and can cause bone to weaken, resulting
in bone pain, arthritis, deformities, and fractures.
Reduction—The restoration of a body part to its original position after displacement, such as the reduction of a fractured bone by bringing ends or fragments
back into original alignment. The useof local or general anesthesia usually accompanies a fracture
reduction. If performed by outside manipulation
only, the reduction is described as closed; if surgery
is necessary, it is described as open.
Rickets—A condition caused by the dietary deficiency of vitamin D, calcium, and usually phosphorus, seen primarily in infancy and childhood,
and characterized by abnormal bone formation.
Traction—The process of placing a bone, limb, or
group of muscles under tension by applying weights
and pulleys. The goal is to realign or immobilize the
part or to relieve pressure on that particular area to
promote healing and restore function.

Prognosis
Fractures involving joint surfaces almost always
lead to some degree of arthritis of the joint. Fractures
can normally be cured with proper first aid and
appropriate aftercare. If determined necessary by a
physician, the fractured site should be manipulated,
realigned, and immobilized as soon as possible.
Realignment has been shown to be much more difficult after six hours. Healing time varies from person
to person with the elderly generally needing more
time to heal completely. A non-union fracture may
result when a fracture does not heal, such as in the
case of an elderly person or an individual with medical complications. Recovery is complete when there
is no bone motion at the fracture site, and x rays
indicate complete healing. Open fractures may lead
to bone infections, which delay the healing process.
Another possible complication is compartment syndrome, a painful condition resulting from the expansion of enclosed tissue and that may occur when a
body part is immobilized in a cast.
1521

Fractures

KEY TERMS

Fragile X syndrome

Prevention
Adequate calcium intake is necessary for strong
bones and can help decrease the risk of fractures.
People who do not get enough calcium in their diets can
take a calcium supplement. Exercise can help strengthen
bones by increasing bone density, thereby decreasing the
risk of fractures from falls. A University of Southern
California study reported that older people who exercised one or more hours per day had approximately half
the incidence of hip fractures as those who exercised
fewer than 30 minutes per day or not at all.
Fractures can be prevented if safety measures are
taken seriously. These measures include using seat
belts in cars and encouraging children to wear protective sports gear. Estrogen replacement for women
past the age of 50 has been shown to help prevent
osteoporosis and the fractures that may result from
this condition. In one study, elderly women on estrogen replacement therapy demonstrated the lowest
occurrence of hip fractures when compared to similar
women not on estrogen replacement therapy.
Resources
BOOKS

Burr, David B. Musculoskeletal Fatigue and Stress Fracture.
Boca Raton, FL: CRC Press, 2001.
Jupiter, J. Fractures and Dislocations of the Hand. St. Louis:
Mosby, 2001.
Moehring, H. David, and Adam Greenspan. Fractures:
Diagnosis and Treatment. New York: McGraw
Hill, 2000.
Ogden, John A. Skeletal Injury in the Child. New York:
Springer Verlag, 2000.
Schenck, Robert C., and Ronnie P. Barnes. Athletic Training
and Sports Medicine. 3rd ed. Chicago: American
Academy of Orthopaedic Surgery, 1999.
ORGANIZATIONS

American Academy of Orthopaedic Surgeons. 6300 North
River Road, Rosemont, IL 60018-4262. (847) 823-7186
or (800) 346-2267. Fax: (847) 823-8125. <http://
orthoinfo.aaos.org/>.
American College of Sports Medicine. 401 W. Michigan St.,
Indianapolis, IN 46202. (317) 637-9200, Fax: (317)
634-7817.
Children’s Orthopedics of Atlanta. <http://
www.childrensortho.com/fractures.htm>.
Nemours Foundation. <http://kidshealth.org/kid/
ill_injure/aches/broken_bones.html>.
OTHER

‘‘About the Human.’’ <http://orthopedics.about.com/
health/orthopedics/blhipfracture.htm>.
Family Practice Notebook.com. <http://www.fpnotebook.com/FRA.htm>.
1522

National Library of Medicine. <http://
medlineplus.adam.com/ency/article/000001.htm>.
University of Iowa. <http://www.vh.org/Providers/
ClinRef/FPHandbook/Chapter06/18-6.html>.

L. Fleming Fallon, Jr., MD, DrPH

Fragile X syndrome
Definition
Fragile X syndrome is the most common form of
inherited mental retardation. Individuals with this
condition have developmental delay, variable levels
of mental retardation, and behavioral and emotional
difficulties. They may also have characteristic physical
traits. Generally, males are affected with moderate
mental retardation and females with mild mental
retardation.

Description
Fragile X syndrome is also known as Martin-Bell
syndrome, Marker X syndrome, and FRAXA syndrome. It is the most common form of inherited mental retardation. Fragile X syndrome is caused by a
mutation in the FMR-1 gene, located on the X
chromosome. The role of the gene is unclear, but it is
probably important in early development.
In order to understand fragile X syndrome it is
important to understand how human genes and
chromosomes influence this condition. Normally,
each cell in the body contains 46 (23 pairs of) chromosomes. These chromosomes consist of genetic material
(DNA) needed for the production of proteins, which
lead to growth, development, and physical/intellectual
characteristics. The first 22 pairs of chromosomes are
the same in males and females. The remaining two
chromosomes are called the sex chromosomes (X and
Y). The sex chromosomes determine whether a person
is male or female. Males have only one X chromosome, which is inherited from the mother at conception, and they receive a Y chromosome from the
father. Females inherit two X chromosomes, one
from each parent. Fragile X syndrome is caused by a
mutation in a gene called FMR-1. This gene is located
on the X chromosome. The FMR-1 gene is thought to
play an important role in the development of the
brain, but the exact way that the gene acts in the
body is not fully understood.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
For reasons not fully understood, the CGG
sequence in the FMR-1 gene can expand to contain
between 54 and 230 repeats. This stage of expansion is
called a premutation. People who carry a premutation
do not usually have symptoms of fragile X syndrome,
although there have been reports of individuals with a
premutation and subtle intellectual or behavioral
symptoms. Individuals who carry a fragile X premutation are at risk to have children or grandchildren with
the condition. Female premutation carriers may also
be at increased risk for earlier onset of menopause;
however, premutation carriers may exist through
several generations of a family and no symptoms of
fragile X syndrome will appear.
The size of the premutation can expand over succeeding generations. Once the size of the premutation
exceeds 230 repeats, it becomes a full mutation and the
FMR-1 gene is disabled. Individuals who carry the full
mutation may have fragile X syndrome. Since the
FMR-1 gene is located on the X chromosome, males
are more likely to develop symptoms than females.
This is because males have only one copy of the
X chromosome. Males who inherit the full mutation
are expected to have mental impairment. A female’s
normal X chromosome may compensate for her
chromosome with the fragile X gene mutation.
Females who inherit the full mutation have an
approximately 50% risk of mental impairment. The
phenomenon of an expanding trinucleotide repeat in
successive generations is called anticipation. Another
unique aspect of fragile X syndrome is that mosaicism
is present in 15–20% those affected by the condition.
Mosaicism is when there is the presence of cells of
two different genetic materials in the same individual.
The mutation involves a short sequence of DNA in
the FMR-1 gene. This sequence is designated CGG.
Normally, the CGG sequence is repeated between six to
54 times. People who have repeats in this range do not
have fragile X syndrome and are not at increased risk to
have children with fragile X syndrome. Those affected by
fragile X syndrome have expanded CGG repeats (over
200) in the first exon of the FMR1 gene (the full mutation)
GALE ENCYCLOPEDIA OF MEDICINE

Fragile X syndrome is inherited in an X-linked
dominant manner (characters are transmitted by
genes on the X chromosome). When a man carries a
premutation on his X chromosome, it tends to be
stable and usually will not expand if he passes it on
to his daughters (he passes his Y chromosome to his
sons). Thus, all of his daughters will be premutation
carriers like he is. When a woman carries a premutation, it is unstable and can expand as she passes it on to
her children, therefore a man’s grandchildren are at
greater risk of developing the syndrome. There is a
50% risk for a premutation carrier female to transmit
an abnormal mutation with each pregnancy. The likelihood for the premutation to expand is related to the
number of repeats present; the higher the number of
repeats, the greater the chance that the premutation
will expand to a full mutation in the next generation.
All mothers of a child with a full mutation are carriers
of an FMR-1 gene expansion. Ninety-nine percent of
patients with fragile X syndrome have a CGG expansion, and less than one percent have a point mutation
or deletion on the FMR1 gene.
Individuals with fragile X syndrome appear normal at birth but their development is delayed. Most
boys with fragile X syndrome have mental impairment. The severity of mental impairment ranges from
learning disabilities to severe mental retardation.
Behavioral problems include attention deficit and
hyperactivity at a young age. Some may show aggressive behavior in adulthood. Short attention span,
poor eye contact, delayed and disordered speech and
language, emotional instability, and unusual hand
mannerisms (hand flapping or hand biting) are also
seen frequently. Characteristic physical traits appear
later in childhood. These traits include a long and
narrow face, prominent jaw, large ears, and enlarged
testes. In females who carry a full mutation, the
physical and behavioral features and mental retardation tend to be less severe. About 50% of females who
have a full mutation are mentally retarded. Other
behavioral characteristics include whirling, spinning,
and occasionally autism.
Children with fragile X syndrome often have frequent ear and sinus infections. Nearsightedness and
lazy eye are also common. Many babies with fragile
X syndrome may have trouble with sucking and some
experience digestive disorders that cause frequent gagging and vomiting. A small percentage of children with
fragile X syndrome may experience seizures. Children
with fragile X syndrome also tend to have loose joints
which may result in joint dislocations. Some children
develop a curvature in the spine, flat feet, and a heart
condition known as mitral valve prolapse.
1523

Fragile X syndrome

Fragile X syndrome affects males and females of
all ethnic groups. It is estimated that there are about
one in 4,000 to one in 6,250 males affected with fragile
X syndrome. There are approximately one-half as
many females with fragile X syndrome as there are
males. The carrier frequency in unaffected females is
one in 100 to one in 600, with one study finding a
carrier frequency of one in 250.

Fragile X syndrome

Diagnosis
Any child with signs of developmental delay of
speech, language, or motor development with no
known cause should be considered for fragile X testing, especially if there is a family history of the condition. Behavioral and developmental problems may
indicate fragile X syndrome, particularly if there is a
family history of mental retardation. Definitive identification of the fragile X syndrome is made by means
of a genetic test to assess the number of CGG
sequence repeats in the FMR-1 gene. Individuals
with the premutation or full mutation may be identified through genetic testing. Genetic testing for the
fragile X mutation can be done on the developing
baby before birth through amniocentesis or chorionic
villus sampling (CVS), and is 99% effective in detecting the condition due to trinucleotide repeat expansion. Prenatal testing should only be undertaken
after the fragile X carrier status of the parents has
been confirmed and the couple has been counseled
regarding the risks of recurrence. While prenatal
testing is possible to do with CVS, the results
can be difficult to interpret and additional testing
may be required.

Treatment
Presently there is no cure for fragile X syndrome.
Management includes such approaches as speech therapy, occupational therapy, and physical therapy. The
expertise of psychologists, special education teachers,
and genetic counselors may also be beneficial. Drugs
may be used to treat hyperactivity, seizures, and other
problems. Establishing a regular routine, avoiding
over-stimulation, and using calming techniques may
also help in the management of behavioral problems.
Children with a troubled heart valve may need to see a
heart specialist and take medications before surgery or
dental procedures. Children with frequent ear and
sinus infections may need to take medications or
have special tubes placed in their ears to drain excess
fluid. Mainstreaming of children with fragile X syndrome into regular classrooms is encouraged because
they do well imitating behavior. Peer tutoring and
positive reinforcement are also encouraged.

Prognosis
Early diagnosis and intensive intervention offer
the best prognosis for individuals with fragile X syndrome. Adults with fragile X syndrome may benefit
from vocational training and may need to live in a
supervised setting. Life span is typically normal.
1524

KEY TERMS
Amniocentesis—A procedure performed at 16–18
weeks of pregnancy in which a needle is inserted
through a woman’s abdomen into her uterus to
draw out a small sample of the amniotic fluid
from around the baby. Either the fluid itself or
cells from the fluid can be used for a variety of
tests to obtain information about genetic disorders
and other medical conditions in the fetus.
CGG or CGG sequence—Shorthand for the DNA
sequence: cytosine-guanine-guanine. Cytosine
and guanine are two of the four molecules, otherwise called nucleic acids, that make up DNA.
Chorionic villus sampling (CVS)—A procedure
used for prenatal diagnosis at 10-12 weeks gestation.
Under ultrasound guidance a needle is inserted either
through the mother’s vagina or abdominal wall and a
sample of cells is collected from around the early
embryo. These cells are then tested for chromosome
abnormalities or other genetic diseases.
Chromosome—A microscopic thread-like structure found within each cell of the body that consists
of a complex of proteins and DNA. Humans have
46 chromosomes arranged into 23 pairs. Changes
in either the total number of chromosomes or their
shape and size (structure) may lead to physical or
mental abnormalities.
FMR-1 gene—A gene found on the X chromosome.
Its exact purpose is unknown, but it is suspected
that the gene plays a role in brain development.
Mitral valve prolapse—A heart defect in which one
of the valves of the heart (which normally controls
blood flow) becomes floppy. Mitral valve prolapse
may be detected as a heart murmur but there are
usually no symptoms.
Premutation—A change in a gene that precedes a
mutation; this change does not alter the function of
the gene.
X chromosome—One of the two sex chromosomes
(the other is Y) containing genetic material that,
among other things, determine a person’s gender.

A 2004 study found that men who are carriers of
the fragile X gene but have not have the mutation
severe enough to have fragile X syndrome may begin
to show signs of tremor disorder, gait instability and
memory impairment as they age. The higher prevalence of these symptoms among grandfathers of children with fragile x syndrome was noted so a study was
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

Kaufmann, Walter E., and Allan L. Reiss. ‘‘Molecular and
Cellular Genetics of Fragile X Syndrome.’’ American
Journal of Medical Genetics 88 (1999): 11–24.
Kirn, Timothy F. ‘‘New Fragile X Often Misdiagnosed
as Parkinson’s.’’ Clinical Psychiatry News March
2004: 84.
ORGANIZATIONS

Arc of the United States (formerly Association for Retarded
Citizens of the US). 500 East Border St., Suite 300,
Arlington, TX 76010. (817) 261-6003. <http://
thearc.org>.
National Fragile X Foundation. PO Box 190488, San
Francisco, CA 94119-0988. (800) 688-8765 or (510)
763-6030. Fax: (510) 763-6223. natlfx@sprintmail.com.
<http://nfxf.org>.
National Fragile X Syndrome Support Group. 206 Sherman
Rd., Glenview, IL 60025. (708) 724-8626.
OTHER

‘‘Fragile X Site Mental Retardation 1; FMR1.’’ Online
Mendelian Inheritance in Man. March 6, 2001. <http://
www3.ncbi.nlm.nih.gov/Omim/>.
Tarleton, Jack, and Robert A. Saul. ‘‘Fragile X Syndrome.’’
GeneClinics March 6, 2001. <http://
www.geneclinics.org>.

Nada Quercia, MS, CCGC
Teresa G. Odle

Frambesia see Yaws
Francisella tularensis infection see Tularemia
Fresh cell therapy see Cell therapy

Description
Ataxia is a condition marked by impaired coordination. Friedreich’s ataxia is the most common inherited ataxia, affecting between 3,000–5,000 people in the
United States. FA is an autosomal recessive disease,
which means that two defective gene copies must be
inherited to develop symptoms, one from each parent.
A person with only one defective gene copy will not
show signs of FA, but may pass along the gene to
offspring. Couples with one child affected by FA
have a 25% chance in each pregnancy of conceiving
another affected child.

Causes and symptoms
Causes
The gene for FA codes for a protein called frataxin. Normal frataxin is found in the cellular energy
structures known as mitochondria, where it is thought
to be involved in regulating the transport of iron. In
FA, the frataxin gene on chromosome 9 is expanded
with nonsense information known as a ‘‘triple repeat.’’
This extra DNA interferes with normal production of
frataxin, thereby impairing iron transport. Normally,
there are 10-21 repeats of the frataxin gene. In FA, this
sequence may be repeated between 200-900 times. The
types of symptoms and severity of FA seems to be
associated with the number of repetitions. Patients
with more copies have more severe symptomatology.
Researchers are still wrestling with how frataxin and
the repeats on chromosome 9 are involved in causing
FA. One theory suggests that FA develops in part
because defects in iron transport prevent efficient use
of cellular energy supplies.
The nerve cells most affected by FA are those in
the spinal cord involved in relaying information
between muscles and the brain. Tight control of movement requires complex feedback between the muscles
promoting a movement, those restraining it, and the
brain. Without this control, movements become uncoordinated, jerky, and inappropriate to the desired
action.
Symptoms

Friedreich’s ataxia
Definition
Friedreich’s ataxia (FA) is an inherited, progressive nervous system disorder causing loss of balance
and coordination.
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms of FA usually first appear between the
ages of 8 and 15, although onset as early as 18 months
or as late as age 25 is possible. The first symptom is
usually gait incoordination. A child with FA may
graze doorways when passing through, for instance,
or trip over low obstacles. Unsteadiness when standing still and deterioration of position sense is common.
Foot deformities and walking up off the heels often
1525

Friedreich’s ataxia

done to investigate their symptoms compared to men
of the same age without the mutation. About 17% of
the grandfathers in their 50s had the condition, 37% of
those in their 60s, 47% of men in their 70s and 75%
of men in their 80s. Often, these men have been diagnosed with other diseases such as Parkinson’s or
Alzheimer’s rather than with fragile X-associated tremor/ataxia syndrome, the name which has been given
to these late symptoms from the fragile x mutation.

Frostbite and frostnip

results from uneven muscle weakness in the legs.
Muscle spasms and cramps may occur, especially
at night.
Ataxia in the arms follows, usually within several
years, leading to decreased hand-eye coordination.
Arm weakness does not usually occur until much
later. Speech and swallowing difficulties are common.
Diabetes mellitus may also occur. Nystagmus, or eye
tremor, is common, along with some loss of visual
acuity. Hearing loss may also occur. A side-to-side
curvature of the spine (scoliosis) occurs in many
cases, and may become severe.
Heartbeat abnormalities occur in about two
thirds of FA patients, leading to shortness of breath
after exertion, swelling in the lower limbs, and frequent complaints of cold feet.

Diagnosis
Diagnosis of FA involves a careful medical history and thorough neurological exam. Lab tests
include electromyography, an electrical test of muscle,
and a nerve conduction velocity test. An electrocardiogram may be performed to diagnose heart
arrhythmia.
Direct DNA testing is available, allowing FA to
be more easily distinguished from other types of
ataxia. The same test may be used to determine the
presence of the genetic defect in unaffected individuals, such as siblings.

Treatment
There is no cure for FA, nor any treatment that
can slow its progress. Amantadine may provide some
limited improvement in ataxic symptoms, but is not
recommended in patients with cardiac abnormalities.
Physical and occupational therapy are used to maintain range of motion in weakened muscles, and to
design adaptive techniques and devices to compensate
for loss of coordination and strength. Some patients
find that using weights on the arms can help dampen
the worst of the uncoordinated arm movements.
Heart arrhythmias and diabetes are treated with
drugs specific to those conditions.

KEY TERMS
Ataxia—A condition marked by impaired coordination.
Scoliosis—An abnormal, side-to-side curvature of
the spine.

death is in the mid-thirties, but may be as late as the
mid-sixties. As of mid-1998, the particular length of
the triple repeat has not been correlated strongly
enough with disease progression to allow prediction
of the course of the disease on this basis.

Prevention
There is no way to prevent development of FA in a
person carrying two defective gene copies.
Resources
BOOKS

Feldman, Eva L. ‘‘Hereditary Cerebellar Ataxias and
Related Disorders.’’ In Cecil Textbook of Medicine,
edited by Russel L. Cecil, et al. Philadelphia: W.B.
Saunders Company, 2000.
Isselbacher, Kurt J., et al. ‘‘Spinocerebellar Degeneration
(Friedreich’s Ataxia).’’ In Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 2001.
ORGANIZATIONS

Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson, AZ 85718. (520) 529-2000 or (800) 572-1717.
<http://www.mdausa.org>.

Rosalyn Carson-DeWitt, MD

Frostbite and frostnip
Definition
Frostbite is the term for damage to the skin and
other tissues caused by freezing. Frostnip is a mild
form of cold injury.

Prognosis
The rate of progression of FA is highly variable.
Most patients lose the ability to walk within 15 years
of symptom onset, and 95% require a wheelchair for
mobility by age 45. Reduction in lifespan from FA
complications is also quite variable. Average age at
1526

Description
In North America, frostbite is largely confined to
Alaska, Canada, and the northern states. Recent years
have witnessed a substantial decline in the number of
cases, probably for several reasons, including better
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Frostbite
Skin exposed to temperatures a little below the
freezing mark can take hours to freeze, but very cold
skin can freeze in minutes or seconds. Air temperature,
wind speed, and moisture all affect how cold the skin
becomes. A strong wind can lower skin temperature
considerably by dispersing the thin protective layer of
warm air that surrounds our bodies. Wet clothing
readily draws heat away from the skin because water
is a potent conductor of heat. The evaporation of
moisture on the skin also produces cooling. For these
reasons, wet skin or clothing on a windy day can lead
to frostbite even if the air temperature is above the
freezing mark.
The extent of permanent injury, however, is
determined not by how cold the skin and the
underlying tissues become but by how long they
remain frozen. Consequently, homeless people and
others whose self-preservation instincts may be
clouded by alcohol or psychiatric illness face a
greater risk of frostbite-related amputation because
they are more likely to stay out in the cold when
prudence dictates seeking shelter or medical attention. Alcohol also affects blood circulation in the
extremities in a way that can increase the severity
of injury (as does smoking). A review of 125
Saskatchewan frostbite cases found a tie to alcohol
in 46% and to psychiatric illness in 17%. Other
risk factors identified by researchers include inadequate clothing, previous cold injury, fatigue, wound
infection, atherosclerosis (an arterial disease), and
diabetes. Driving in poor weather can also be dangerous: vehicular failure was a predisposing factor
in 15% of the Saskatchewan cases.
Three nearly simultaneous physiological processes underlie frostbite injury: tissue freezing, tissue hypoxia, and the release of inflammatory
mediators. Tissue freezing causes ice crystal formation and other changes that damage and eventually
kill cells. Much of this harm occurs because the ice
produces pressure changes that cause water (crucial
for cell survival) to flow out of the cells. Tissue
GALE ENCYCLOPEDIA OF MEDICINE

hypoxia (oxygen deficiency) occurs when the
blood vessels in the hands, feet, and other extremities narrow in response to cold. Among its many
tasks, blood transfers body heat to the skin, which
then dissipates the heat into the environment.
Blood vessel narrowing is the body’s way of protecting vital internal organs at the expense of the
extremities by reducing heat flow away from the
core. However, blood also carries life-sustaining
oxygen to the skin and other tissues, and narrowed
vessels result in oxygen starvation. Narrowing also
causes acidosis (an increase in tissue acidity) and
increases blood viscosity (thickness). Ultimately,
blood stops flowing through the capillaries (the
tiny blood vessels that connect the arteries and
veins) and blood clots form in the arterioles
and venules (the smallest arteries and veins).
Damage also occurs to the endothelial cells that
line the blood vessels. Hypoxia, blood clots, and
endothelial damage lead, in turn, to the release of
inflammatory mediators (substances that act as
links in the inflammatory process), which promote
further endothelial damage, hypoxia, and cell
destruction.
Frostbite is classified by degree of injury (first,
second, third, or fourth), or simply divided into two
types, superficial (corresponding to first- or seconddegree injury) and deep (corresponding to third- or
fourth-degree injury). Most frostbite injuries affect the
feet or hands. The remaining 10% of cases typically
involve the ears, nose, cheeks, or penis. Once frostbite
sets in, the affected part begins to feel cold and,
usually, numb; this is followed by a feeling of clumsiness. The skin turns white or yellowish. Many patients
experience severe pain in the affected part during
rewarming treatment and an intense throbbing pain
that arises two or three days later and can last days or
weeks. As the skin begins to thaw during treatment,
edema (excess tissue fluid) often accumulates, causing
swelling. In second- and higher-degree frostbite, blisters appear. Third-degree cases produce deep, bloodfilled blisters and, during the second week, a hard
black eschar (scab). Fourth-degree frostbite penetrates below the skin to the muscles, tendons, nerves,
and bones. In severe cases of frostbite the dead tissue
can mummify and drop off. Infection is also a
possibility.
Frostnip
Like frostbite, frostnip is associated with ice crystal formation in the tissues, but no tissue destruction
occurs and the crystals dissolve as soon as the skin is
warmed. Frostnip affects areas such as the earlobes,
1527

Frostbite and frostnip

winter clothing and footwear and greater public
understanding of how to avoid cold-weather dangers.
At the same time, the nature of the at-risk population
has changed as rising numbers of homeless people
have made frostbite an urban as well as a rural public
health concern. The growing popularity of outdoor
winter activities has also expanded the at-risk
population.

Frostbite and frostnip

cheeks, nose, fingers, and toes. The skin turns pale and
one experiences numbness or tingling in the affected
part until warming begins.

Diagnosis
Frostbite diagnosis relies on a physical examination and may also include conventional radiography
(x rays), angiography (x-ray examination of the blood
vessels using an injected dye to provide contrast),
thermography (use of a heat-sensitive device for measuring blood flow), and other techniques for predicting the course of injury and identifying tissue that
requires surgical removal. During the initial treatment
period, however, a physician cannot judge how a case
will progress. Diagnostic tests only become useful
three to five days after rewarming, once the blood
vessels have stabilized.

Treatment
Frostbite
Emergency medical help should always be summoned whenever frostbite is suspected. While waiting for help to arrive, one should, if possible, remove
wet or tight clothing and put on dry, loose clothing
or wraps. A splint and padding are used to protect
the injured area. Rubbing the area with snow or
anything else is dangerous. The key to prehospital
treatment is to avoid partial thawing and refreezing,
which releases more inflammatory mediators and
makes the injury substantially worse. For this reason, the affected part must be kept away from heat
sources such as campfires and car heaters. Experts
advise rewarming in the field only when emergency
help will take more than two hours to arrive and
refreezing can be prevented.
Because the outcome of a frostbite injury cannot
be predicted at first, all hospital treatment follows
the same route. Treatment begins by rewarming the
affected part for 15–30 minutes in water at a temperature of 104–108 8F (40–42.2 8C). This rapid
rewarming halts ice crystal formation and dilates
narrowed blood vessels. Aloe vera (which acts
against inflammatory mediators) is applied to the
affected part, which is then splinted, elevated, and
wrapped in a dressing. Depending on the extent of
injury, blisters may be debrided (cleaned by removing foreign material) or simply covered with aloe
vera. A tetanus shot and, possibly, penicillin, are
used to prevent infection, and the patient is given
ibuprofen to combat inflammation. Narcotics are
needed in most cases to reduce the excruciating
1528

A human hand with frostbite. (Photo Researchers, Inc.
Reproduced by permission.)

pain that occurs as sensation returns during rewarming. Except when injury is minimal, treatment generally requires a hospital stay of several days, during
which hydrotherapy and physical therapy are used to
restore the affected part to health. Experts recommend a cautious approach to tissue removal, and
advise that 22–45 days must pass before a decision
on amputation can safely be made.
Frostnip
Frostnipped fingers are helped by blowing
warm air on them or holding them under one’s
armpits. Other frostnipped areas can be covered
with warm hands. The injured areas should never
be rubbed.

Alternative treatment
Alternative practitioners suggest several kinds
of treatment to speed recovery from frostbite after
leaving the hospital. Bathing the affected part in
warm water or using contrast hydrotherapy can
help enhance circulation. Contrast hydrotherapy
involves a series of hot and cold water applications.
A hot compress (as hot as the patient can stand) is
applied to the affected area for three minutes followed by an ice cold compress for 30 seconds.
These applications are repeated three times each,
ending with the cold compress. Nutritional therapy
to promote tissue growth in damaged areas may
also be helpful. Homeopathic and botanical therapies may also assist recovery from frostbite.
Homeopathic Hypericum (Hypericum perforatum)
is recommended when nerve ending are affected
(especially in the fingers and toes) and Arnica
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The rapid rewarming approach to frostbite treatment, pioneered in the 1980s, has proved to be much
more effective than older methods in preventing
tissue loss and amputation. A study of 56 first-,
second-, and third-degree frostbite patients treated
with rapid rewarming in 1982–85 found that 68%
recovered without tissue loss, 25% experienced
some tissue loss, and 7% needed amputation. In a
comparison group of 98 patients, treatment using
older methods resulted in a tissue loss rate of nearly
35% and an amputation rate of nearly 33%.
Although the comparison group included a higher
proportion of second- and third-degree cases, the
difference in treatment results was determined to be
statistically significant.
The extreme throbbing pain that many frostbite
sufferers endure for days or weeks after rewarming is
not the only prolonged symptom of frostbite. During
the first weeks or months, people often experience
tingling, a burning sensation, or a sensation resembling shocks from an electric current. Other possible
consequences of frostbite include skin—color changes,
nail deformation or loss, joint stiffness and pain,
hyperhidrosis (excessive sweating), and heightened
sensitivity to cold. For everyone, a degree of sensory
loss lasting at least four years—and sometimes a lifetime—is inevitable.

Prevention
With the appropriate knowledge and precautions, frostbite can be prevented even in the coldest
and most challenging environments. Appropriate
clothing and footwear are essential. To prevent
heat loss and keep the blood circulating properly,
clothing should be worn loosely and in layers.
Covering the hands, feet, and head is also crucial
for preventing heat loss. Outer garments need to be
wind and water resistant, and wet clothing and
footwear must be replaced as quickly as possible.
Alcohol and drugs should be avoided because of
their harmful effects on judgment and reasoning.
Experts also warn against alcohol use and smoking
in the cold because of the circulatory changes they
produce. Paying close attention to the weather
GALE ENCYCLOPEDIA OF MEDICINE

report before venturing outdoors and avoiding
unnecessary risks such as driving in isolated areas
during a blizzard are also important.
Resources
PERIODICALS

Reamy, Brian V. ‘‘Frostbite: Review and Current
Concepts.’’Journal of the American Board of Family
Practice January-February 1998: 34-40.

Howard Baker

Frostnip see Frostbite and frostnip
FSH test see Follicle-stimulating
hormone test

Fugu poisoning
Definition
Fugu poisoning occurs when a person eats the
flesh of a fugu, also known as a puffer fish, which
contains lethal toxins.

Description
Fugu, also known as puffer fish, blowfish, or
globefish, has long been a food delicacy in Japan, but
has only been introduced in the United States in the
last 30-40 years. The fugu and related species may
contain a tetrodotoxin, an extremely potent neurotoxin and one of the most toxic substances known,
which produces critical illness and often death.
Between January 1 and April 1, 2002, at least 10
cases of fugu poisoning were reported in the United
States, according to the Centers for Disease Control
and Prevention (CDC) in Atlanta. All persons recovered from the poisonings. All of the fish came from the
Atlantic Ocean off the coast of Titusville, Florida.
Fugu caught in southern U.S. waters, such as the
Gulf of Mexico, may also be toxic. Tetrodotoxin has
been detected in pufferfish throughout the Pacific
Ocean and the Baja California coastal region. Cases
of fugu poisoning are sporadically diagnosed, but
many more are not recognized or reported. The earliest cases reported to the CDC involved poisonings in
Florida during the mid-1970s. Since 1950, only three
known fatalities have occurred in the United States, all
in Florida.
1529

Fugu poisoning

(Arnica montana) is prescribed for shock. Cayenne
pepper (Capsicum frutescens) can enhance circulation and relieve pain. Drinking hot ginger (Zingiber
officinale) tea also aids circulation. Other possible
approaches include acupuncture to avoid permanent
nerve damage and oxygen therapy.

Fugu poisoning

The dangers of puffer fish consumption have long
been recognized. Artifacts recovered from an
Egyptian tomb indicate that puffer fish poisoning has
been known since approximately 2400-2700 B.C. In
journals covering expeditions from 1772-1775, Pacific
explorer Captain James Cook provided a vivid
description of what some believe to be puffer fish
poisoning. Fugu are found in waters throughout the
world. Scientists have found that toxic fugu have
unique exocrine glands for the secretion of tetrodotoxin. The fish appear to actively produce the toxin,
rather than passively acquire it from the environment.
For these fish, tetrodotoxin may serve as a natural
defense mechanism to repel predators. The flesh of
the fugu is generally eaten raw in paper-thin slices,
known as sashimi. Part of the reported delight in
eating fugu is the tingling oral sensation induced by
minute amounts of tetrodotoxin in the flesh. For this
reason, eating fugu is considered an ‘‘experience,’’
rather than just a meal in Japan. The experience is
expensive, however, since a plate of this delicacy can
cost as much as $500.

Causes & symptoms
The most common symptoms of fugu poisioning
are tingling and burning of the mouth and tongue,
numbness, drowsiness, and incoherent speech. These
symptoms usually occur 30 minutes to two hours after
ingestion of the fish, depending on the amount of toxin
ingested. In severe cases, ataxia (the inability to coordinate the movements of muscles), muscle weakness,
hypotension (low blood pressure) and cardiac arrhythmias (irregular heartbeat) may develop, followed by
muscle twitching and respiratory paralysis, and death
can occur. In several cases, people died within
17 minutes after eating pufferfish.

Diagnosis
The initial diagnosis is usually made by observation of early symptoms, including an abnormal or
unexplained tingling, pricking, or burning sensation
on the skin around the mouth and throat. Definitive
diagnosis can only be made in a medical laboratory by
examination of the ingested fish and identification of
the specific toxins. Ill persons should be advised to
proceed to a hospital emergency department and contact their local poison control center.

Treatment
There is no antidote for fugu poisoning, therefore treatment is limited to supportive measures
1530

KEY TERMS
Ataxia—A lack of muscle control.
Arrhythmia—An irregularity in the normal rhythm
or force of the heartbeat.
Atropine—A poisonous alkaloid obtained from
belladonna or related plants, used medically to
dilate the pupils of the eyes and to stop spasms.
Endoscopy—The use of a medical instrument consisting of a long tube inserted into the body, usually
through a small incision, for diagnostic examination and surgical procedures.
Exocrine—Relating to external secretion glands,
such as sweat glands or salivary glands that release
a secretion through a duct to the surface of an
organ.
Hypotension—Low blood pressure.
Lavage—The washing out of a hollow body organ,
for example, the stomach, using a flow of water.
Neurotoxin—A substance that damages, destroys,
or impairs the functioning of nerve tissue.

and the removal of the unabsorbed toxin. If spontaneous vomiting does not occur, it should be
induced. Gastric lavage (stomach washing) with
an alkaline solution has been suggested, as well as
endoscopy to remove the poison from the proximal
small bowel. Following lavage, activated charcoal is
reported to effectively bind the toxin. Other steps
include administration of oxygen, assisted breathing, intravenous atropine for bradycardia (slow
heartbeat) and intravenous fluids, along with dopamine, to manage hypotension. Since tetrodotoxins
and opiates are similar, use of an opiate antagonist
may be useful, according to the American Academy
of Family Physicians.

Alternative treatment
There is no alternative medicine treatment for
fugu poisoning.

Prognosis
The mortality rate may be as high as 60%.
Epidemiologic evidence suggests that recovery can be
expected if an affected person survives beyond
24 hours. After 24 hours, a person with fugu poisoning
usually makes a full recovery.
GALE ENCYCLOPEDIA OF MEDICINE

The only prevention is not to eat any of the species
of fugu that contain toxins.

ORGANIZATIONS

American Association of Poison Control Centers. 3201
New Mexico Ave., Suite 330, Washington, DC 20016.
(292) 362-7217. info@aapcc.org. http://
www.aapcc.org.

Resources
Ken R. Wells

BOOKS

Olson, Kent R. Poisoning & Drug Overdose New York City:
McGraw-Hill, 2003.

Fugue see Dissociative disorders

PERIODICALS

FUO see Fever of unknown origin

Currie, Bart J. ‘‘Marine Antivenoms.’’Journal of
Toxicology: Clinical Toxicology (April 2003): 301-308.
‘‘Fugu Fish Sequenced.’’Applied Genetics News (August
2002): 0.
Scully, Mary-Louise. ‘‘Tingling Away in Titusville, Florida.’’
Infectious Disease Alert (August 1, 2002): 165-167.

Furosemide see Diuretics

GALE ENCYCLOPEDIA OF MEDICINE

Furunculosis see Boils
Fusobacterium infection see Anaerobic
infections

1531

Fugu poisoning

Prevention

G
Galactorrhea
Definition
Galactorrhea is the secretion of breast milk in
men, or in women who are not breastfeeding an infant.

Description
Lactation, or the production of breast milk, is a
normal condition occurring in women after delivery
of a baby. Many women who have had children may
even be able to express a small amount of breast
milk from the nipple up to two years after childbirth.
Galactorrhea, or hyperlactation, however, is a rare condition that can occur in both men and women, where a
white or grayish fluid is secreted by the nipples of both
breasts. While this condition is not serious in itself, galactorrhea can indicate more serious conditions, including
hormone imbalances or the presence of tumors.

Causes and symptoms
Causes
Galactorrhea is associated with a number of conditions. The normal production of breast milk is
controlled by a hormone called prolactin, which is
secreted by the pituitary gland in the brain. Any
condition that upsets the balance of hormones in
the blood or the production of hormones by the
pituitary gland or sexual organs can stimulate the
production of prolactin.
Often, a patient with galactorrhea will have a high
level of prolactin in the blood. A tumor in the pituitary
gland can cause this overproduction of prolactin.
At least 30% of women with galactorrhea, menstrual
abnormalities, and high prolactin levels have a
pituitary gland tumor. Other types of brain tumors,
head injuries, or encephalitis (an infection of the brain)
can also cause galactorrhea.
GALE ENCYCLOPEDIA OF MEDICINE

Tumors or growths in the ovaries or other reproductive organs in women, or in the testicles or related
sexual organs of men, can also stimulate the production
of prolactin. Any discharge of fluid from the breast after
a woman has passed menopause may indicate breast
cancer. However, most often the discharge associated
with breast cancer will be from one breast only. In
galactorrhea both breasts are usually involved. The
presence of blood in the fluid discharged from the
breast could indicate a benign growth in the breast tissue
itself. In approximately 10–15% of patients with blood
in the fluid, carcinoma of the breast tissue is present.
A number of medications and drugs can also
cause galactorrhea as a side-effect. Hormonal therapies (like oral contraceptives), drugs for treatment of
depression or other psychiatric conditions, tranquilizers, morphine, heroin, and some medications for high
blood pressure can cause galactorrhea.
Several normal physiologic situations can cause
production of breast milk. Nipple stimulation in men or
women during sexual intercourse may induce lactation,
for women particularly during or just after pregnancy.
Even after extensive testing, no specific cause can
be determined for some patients with galactorrhea.
Symptoms
The primary symptom of galactorrhea is the discharge of milky fluid from both breasts. In women,
galactorrhea may be associated with infertility, menstrual cycle irregularities, hot flushes, or amenorrhea–
a condition where menstruation stops completely.
Men may experience loss of sexual interest and
impotence. Headaches and visual disturbances have
also been associated with some cases of galactorrhea.

Diagnosis
Galactorrhea is generally considered a symptom
that may indicate a more serious problem. Collection
1533

Galactosemia

of a thorough medical history, including pregnancies,
surgeries, and consumption of drugs and medications is
a first step in diagnosing the cause of galactorrhea. A
physical examination, along with a breast examination,
will usually be conducted. Blood and urine samples
may be taken to determine levels of various hormones
in the body, including prolactin and compounds related
to thyroid function.
A mammogram (an x ray of the breast) or an
ultrasound scan (using high frequency sound waves)
might be used to determine if there are any tumors or
cysts present in the breasts themselves. If a tumor of
the pituitary gland is suspected, a series of computer
assisted x rays called a computed tomography scan
(CT scan) may be done. Another procedure that may
be useful is a magnetic resonance imaging (MRI) scan
to locate tumors or abnormalities in tissues.

Treatment
Treatment for galactorrhea will depend on the
cause of the condition and the symptoms. The drug
bromocriptine is often prescribed first to reduce the
secretion of prolactin and to decrease the size of
pituitary tumors. This drug will control galactorrhea
symptoms and in many cases may be the only
therapy necessary. Oral estrogen and progestins
(hormone pills, like birth control pills) may control
symptoms of galactorrhea for some women. Surgery
to remove a tumor may be required for patients
who have more serious symptoms of headache and
vision loss, or if the tumor shows signs of enlargement despite drug treatment. Radiation therapy has
also been used to reduce tumor size when surgery is
not possible or not totally successful. A combination
of drug, surgery, and radiation treatment can also
be used.
Galactorrhea is more of a nuisance than a real
threat to health. While it is important to find the
cause of the condition, even if a tumor is discovered
in the pituitary gland, it may not require treatment.
With very small, slow-growing tumors, some physicians may suggest a ‘‘wait and see’’ approach.

Prognosis
Treatment with bromocriptine is usually effective
in stopping milk secretion, however, symptoms may
recur if drug therapy is discontinued. Surgical removal
or radiation treatment may correct the problem
permanently if it is related to a tumor. Frequent
monitoring of hormone status and tumor size may be
recommended.
1534

KEY TERMS
Amenorrhea—Abnormal cessation of menstruation.
Bromocriptine—Also known as Parlodel, the main
drug used to treat galactorrhea by reducing levels of
the hormone prolactin.
Hyperlactation—Another term for galactorrhea.
Lactation—The production of breast milk.

Prevention
There is no way to prevent galactorrhea. If the
condition is caused by the use of a particular drug, a
patient may be able to switch to a different drug that
does not have the side-effect of galactorrhea.
Resources
BOOKS

‘‘Galactorrhea.’’ In Current Medical Diagnosis & Treatment,
1998. 37th ed. Stamford: Appleton & Lange, 1997.

Altha Roberts Edgren

Galactosemia
Definition
Galactosemia is an inherited disease in which the
transformation of galactose to glucose is blocked,
allowing galactose to increase to toxic levels in the
body. If galactosemia is untreated, high levels of galactose cause vomiting, diarrhea, lethargy, low blood
sugar, brain damage, jaundice, liver enlargement,
cataracts, susceptibility to infection, and death.

Description
Galactosemia is a rare but potentially lifethreatening disease that results from the inability to
metabolize galactose. Serious consequences from
galactosemia can be prevented by screening newborns
at birth with a simple blood test.
Galactosemia is an inborn error of metabolism.
‘‘Metabolism’’ refers to all chemical reactions that
take place in living organisms. A metabolic pathway
is a series of reactions where the product of each
step in the series is the starting material for the
next step. Enzymes are the chemicals that help
GALE ENCYCLOPEDIA OF MEDICINE

Sugars are sometimes called ‘‘the energy molecules,’’ and galactose and glucose are both sugars.
For galactose to be utilized for energy, it must be
transformed into something that can enter the
metabolic pathway that converts glucose into energy
(plus water and carbon dioxide). This is important
for infants because they typically get most of their
nutrient energy from milk, which contains a high
level of galactose. Each molecule of lactose, the
major sugar constituent of milk, is made up of a
molecule of galactose and a molecule of glucose, and
so galactose makes up 20% of the energy source of a
typical infant’s diet.
Three enzymes are required to convert galactose
into glucose-1-phosphate (a phosphorylated glucose
that can enter the metabolic pathway that turns
glucose into energy). Each of these three enzymes is
encoded by a separate gene. If any of these enzymes
fail to function, galactose build-up and galactosemia
result. Thus, there are three types of galactosemia with
a different gene responsible for each.
Every cell in a person’s body has two copies of
each gene. Each of the forms of galactosemia is
inherited as a recessive trait, which means that galactosemia is only present in individuals with
two mutated copies of one of the three genes. This
also means that carriers, with only one copy of a gene
mutation, will not be aware that they are carrying
a mutation (unless they have had a genetic test), as it
is masked by the normal gene they also carry and
they have no symptoms of the disease. For each step
in the conversion of galactose to glucose, if only one
of the two copies of the gene controlling that step is
normal (i.e. for carriers), enough functional enzyme
is made so that the pathway is not blocked at that
step. If a person has galactosemia, both copies of the
gene coding for one of the enzymes required to convert glucose to galactose are defective and the pathway becomes blocked. If two carriers of the same
defective gene have children, the chance of any of
their children getting galactosemia (the chance of a
child getting two copies of the defective gene) is 25%
(one in four) for each pregnancy.
Classic galactosemia occurs in the United States
about one in every 50,000–70,000 live births.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Galactosemia I
Galactosemia I (also called classic galactosemia),
the first form to be discovered, is caused by defects in
both copies of the gene that codes for an enzyme called
galactose-1-phosphate uridyl transferase (GALT).
There are 30 known different mutations in this gene
that cause GALT to malfunction.
Newborns with galactosemia I appear normal at
birth, but begin to develop symptoms after they are
given milk for the first time. Symptoms include vomiting, diarrhea, lethargy (sluggishness or fatigue), low
blood glucose, jaundice (a yellowing of the skin and
eyes), enlarged liver, protein and amino acids in the
urine, and susceptibility to infection, especially from
gram negative bacteria. Cataracts (a grayish white film
on the eye lens) can appear within a few days after birth.
People with galactosemia frequently have symptoms as
they grow older even though they have been given a
galactose-free diet. These symptoms include speech
disorders, cataracts, ovarian atrophy, and infertility in
females, learning disabilities, and behavioral problems.
Galactosemia II
Galactosemia II is caused by defects in both copies
of the gene that codes for an enzyme called galactokinase (GALK). The frequency of occurrence of
galactosemia II is about one in 100,000–155,000 births.
Galactosemia II is less harmful than galactosemia
I. Babies born with galactosemia II will develop cataracts at an early age unless they are given a galactosefree diet. They do not generally suffer from liver
damage or neurologic disturbances.
Galactosemia III
Galactosemia III is caused by defects in the gene
that codes for an enzyme called uridyl diphosphogalactose-4-epimerase (GALE). This form of galactosemia is very rare.
There are two forms of galactosemia III, a severe
form, which is exceedingly rare, and a benign form.
The benign form has no symptoms and requires no
special diet. However, newborns with galactosemia
III, including the benign form, have high levels of
galactose-1-phosphate that show up on the initial
screenings for elevated galactose and galactose1-phosphate. This situation illustrates one aspect of
the importance of follow-up enzyme function tests.
Tests showing normal levels of GALT and GALK
allow people affected by the benign form of galactosemia III to enjoy a normal diet.
1535

Galactosemia

the reactions occur. Their ability to function
depends on their structure, and their structure is
determined by the deoxyribonucleic acid (DNA)
sequence of the genes that encode them. Inborn
errors of metabolism are caused by mutations in
these genes which do not allow the enzymes to function properly.

Galactosemia

The severe form has symptoms similar to those of
galactosemia I, but with more severe neurological
problems, including seizures. Only two cases of this
rare form had been reported as of 1997.

Diagnosis
The newborn screening test for classic galactosemia is quick and straightforward; all but three states
require testing on all newborns. Blood from a baby
who is two to three days old is usually first screened for
high levels of galactose and galactose-1-phosphate. If
either of these compounds is elevated, further tests are
performed to find out which enzymes (GALT, GALK,
or GALE) are present or missing. DNA testing may
also be performed to confirm the diagnosis.
If there is a strong suspicion that a baby has
galactosemia, galactose is removed from the diet
right away. In this case, an initial screen for galactose
or galactose-1-phosphate will be meaningless. In the
absence of galactose in the diet, this test will be negative whether the baby has galactosemia or not. In this
case, tests to measure enzyme levels must be given to
find out if the suspected baby is indeed galactosemic.
In addition, galactosemic babies who are refusing
milk or vomiting will not have elevated levels of galactose or galactose phosphate, and their condition will
not be detected by the initial screen. Any baby with
symptoms of galactosemia (for example, vomiting)
should be given enzyme tests.

Treatment
Galactosemia I and II are treated by removing
galactose from the diet. Since galactose is a breakdown product of lactose, the primary sugar constituent
of milk, this means all milk and foods containing milk
products must be totally eliminated. Other foods like
legumes, organ meats, and processed meats also contain considerable galactose and must be avoided. Pills
that use lactose as a filler must also be avoided. Soybased and casein hydrolysate-based formulas are
recommended for infants with galactosemia.
Treatment of the severe form of galactosemia III
with a galactose-restricted diet has been tried, but this
disorder is so rare that the long-term effects of this
treatment are unknown.

KEY TERMS
Casein hydrolysate—A preparation made from the
milk protein casein, which is hydrolyzed to break it
down into its constituent amino acids. Amino acids
are the building blocks of proteins.
Catalyst—A substance that changes the rate of a
chemical reaction, but is not physically changed by
the process.
Enzyme—A protein that catalyzes a biochemical
reaction or change without changing its own structure or function.
Galactose—One of the two simple sugars, together
with glucose, that makes up the protein, lactose,
found in milk. Galactose can be toxic in high levels.
Glucose—One of the two simple sugars, together
with galactose, that makes up the protein, lactose,
found in milk. Glucose is the form of sugar that is
usable by the body to generate energy.
Lactose—A sugar made up of of glucose and galactose. It is the primary sugar in milk.
Metabolic pathway—A sequence of chemical
reactions that lead from some precursor to a
product, where the product of each step in the
series is the starting material for the next step.
Metabolism—The total combination of all of the
chemical processes that occur within cells and
tissues of a living body.
Recessive trait—An inherited trait or characteristic
that is outwardly obvious only when two copies of
the gene for that trait are present.

the liver, and death. About 75% of the untreated
babies die within the first two weeks of life. On the
other hand, with treatment, a significant proportion of
people with galactosemia I can lead nearly normal
lives, although speech defects, learning disabilities,
and behavioral problems are common. A 2004 study
revealed that children and adolescents with classic
galactosemia often have lower quality of life than
peers without the disease, exhibiting problems with
cognition (thinking and intellectual skills) and social
function. In addition, cataracts due to galactosemia II
can be completely prevented by a galactose-free diet.

Prognosis
Early detection in the newborn period is the key to
controlling symptoms. Long-term effects in untreated
babies include severe mental retardation, cirrhosis of
1536

Prevention
Since galactosemia is a recessive genetic disease,
the disease is usually detected on a newborn screening
GALE ENCYCLOPEDIA OF MEDICINE

Resources

most absorptive surface in the body. After a meal,
the gallbladder’s muscular walls contract to deliver
the bile back through the cystic duct and eventually
into the small intestine, where the bile can help
digest food.

Demographics
About 5,000 people are diagnosed with gallbladder cancer each year in the United States, making it the
fifth most common gastrointestinal cancer. It is more
common in females than males and most patients are
elderly. Southwest American Indians have a particularly high incidence— six times that of the general
population.

PERIODICALS

Bosch, Annet M., et al. ‘‘Living With Classical
Galactosmeia: Health-related Quality of Life
Consequences.’’ Pediatrics May 2004: 1385–1387.
ORGANIZATIONS

Association for Neuro-Metabolic Disorders. 5223
Brookfield Lane, Sylvania, OH 43560. (419) 885-1497.
Metabolic Information Network. PO Box 670847, Dallas,
TX 75367-0847. (214) 696-2188 or (800) 945-2188.
Parents of Galactosemic Children, Inc. 2148
Bryton Dr., Powell OH 43065. <http://
www.galactosemia.org/index.htm>.
OTHER

‘‘GeneCards: Human Genes, Proteins and Diseases.’’
<http://bioinfo.weizmann.ac.il/cards/>.
‘‘Vermont Newborn Screening Program: Galactosemia.’’
<http://www.vtmednet.org/m145037/vhgi_mem/
nbsman/galacto.htm>.

Amy Vance, MS, CGC
Teresa G. Odle

Gallbladder cancer
Definition
Cancer of the gallbladder is cancer of the pearshaped organ that lies on the undersurface of the liver.

Description
Bile from the liver is funneled into the gallbladder
by way of the cystic duct. Between meals, the gallbladder stores a large amount of bile. To do this, it must
absorb much of the water and electrolytes from the
bile. In fact, the inner surface of the gallbladder is the
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Gallstones are the most significant risk factor for
the development of gallbladder cancer. Roughly 75 to
90 percent of patients with gallbladder cancer also
have gallstones. Larger gallstones are associated with
a higher chance of developing gallbladder cancer.
Chronic inflammation of the gallbladder from infection also increases the risk for gallbladder cancer.
Unfortunately, sometimes cancer of the gallbladder does not produce symptoms until late in the disease. When symptoms are evident, the most common
is pain in the upper right portion of the abdomen,
underneath the right ribcage. Patients with gallbladder
cancer may also report symptoms such as nausea,
vomiting, weakness, jaundice, skin itching, fever, chills,
poor appetite, and weight loss.

Diagnosis
Gallbladder cancer is often misdiagnosed because
it mimics other more common conditions, such as
gallstones, cholecystitis, and pancreatitis. But the imaging tests that are utilized to evaluate these other conditions can also detect gallbladder cancer. For
example, ultrasound is a quick, noninvasive imaging
test that reliably diagnoses gallstones and cholecystitis. It can also detect the presence of gallbladder cancer
as well as show how far the cancer has spread. If
cancer is suspected, a computed tomography scan is
useful in confirming the presence of an abnormal mass
and further demonstrating the size and extent of the
tumor. Cholangiography, usually performed to evaluate a patient with jaundice, can also detect gallbladder
cancer.
There are no specific laboratory tests for gallbladder cancer. Tumors can obstruct the normal flow of
1537

Gallbladder cancer

test, since most people are unaware that they are
carriers of a gene mutation causing the disease. For
couples with a previous child with galactosemia,
prenatal diagnosis is available to determine whether
a pregnancy is similarly affected. Families in which a
child has been diagnosed with galactosemia can have
DNA testing which can enable other more distant
relatives to determine their carrier status. Prospective
parents can then use that information to conduct
family planning or to prepare for a child with special
circumstances. Children born with galactosemia
should be put on a special diet right away, to reduce
the symptoms and complications of the disease.

Gallbladder cancer

bile from the liver to the small intestine. Bilirubin, a
component of bile, builds up within the liver and is
absorbed into the bloodstream in excess amounts.
This can be detected in a blood test, but it can also
manifest clinically as jaundice. Elevated bilirubin
levels and clinical jaundice can also occur with other
conditions, such as gallstones.
On occasion, gallbladder cancer is diagnosed incidentally. About one percent of all patients who have
their gallbladder removed for symptomatic gallstones
are found to have gallbladder cancer. The cancer is
found either by the surgeon or by the pathologist who
inspects the gallbladder with a microscope.

Treatment
Staging of gallbladder cancer is determined by the
how far the cancer has spread. The effectiveness of
treatment declines as the stage progresses. Stage I
cancer is confined to the wall of the gallbladder.
Approximately 25% of cancers are at this stage at
the time of diagnosis. Stage II cancer has penetrated
the full thickness of the wall, but has not spread to
nearby lymph nodes or invaded adjacent organs. Stage
III cancer has spread to nearby lymph nodes or has
invaded the liver, stomach, colon, small intestine, or
large intestine. Stage IV disease has invaded very
deeply into two or more adjacent organs or has spread
to distant lymph nodes or organs by way of metastasis.
Early Stage I cancers involving only the innermost
layer of the gallbladder wall can be cured by simple
removal of the gallbladder. Cancers at this stage are
sometimes found incidentally when the gallbladder is
removed in the treatment of gallstones or cholecystitis.
The majority of patients have good survival rates. Late
Stage I cancers, which involve the outer muscular
layers of the gallbladder wall, are generally treated in
the same way as Stage II or III cancers. Removal of the
gallbladder is not sufficient for these stages. The surgeon also removes nearby lymph nodes as well as a
portion of the adjacent liver (radical surgery). Survival
rates for these patients are considerably worse than for
those with early Stage I disease. Patients with early
Stage IV disease may benefit from radical surgery, but
the issue is controversial. Late Stage IV cancer has
spread too extensively to allow complete excision.
Surgery is not an option for these patients.
Other therapies
When long-term survival is not likely, the focus of
therapy shifts to improving quality of life. Jaundice
and blockage of the stomach are two problems faced
by patients with advanced cancer of the gallbladder.
1538

KEY TERMS
Cholangiography—Radiographic examination of
the bile ducts after injection with a special dye
Cholecystitis—Inflammation of the gallbladder,
usually due to infection
Computed tomography—A radiology test by which
images of cross-sectional planes of the body are
obtained
Jaundice—Yellowish staining of the skin and eyes
due to excess bilirubin in the bloodstream
Metastasis—The spread of tumor cells from one
part of the body to another through blood vessels
or lymphatic vessels
Pancreatitis—Inflammation of the pancreas
Stent—Slender hollow catheter or rod placed
within a vessel or duct to provide support or maintain patency
Ultrasound—A radiology test utilizing high frequency
sound waves

These can be treated with surgery, or alternatively, by
special interventional techniques employed by the gastroenterologist or radiologist. A stent can be placed
across the bile ducts in order to re-establish the flow of
bile and relieve jaundice. A small feeding tube can be
placed in the small intestine to allow feeding when the
stomach is blocked. Pain may be treated with conventional pain medicines or a celiac ganglion nerve block.
Current chemotherapy or radiation therapy cannot
cure gallbladder cancer, but they may offer some
benefit in certain patients. For cancer that is too
advanced for surgical cure, treatment with chemotherapeutic agents such as 5-fluorouracil may lengthen
survival for a few months. The limited benefit of
chemotherapy must be weighed carefully against its
side effects. Radiation therapy is sometimes used after
attempted surgical resection of the cancer to extend
survival for a few months or relieve jaundice.
Resources
BOOKS

Abeloff, Martin D. ‘‘Gallbladder Carcinoma.’’ In Clinical
Oncology. 2nd ed. New York: Churchill Livingstone,
2000, pp.1730-1737.
Ahrendt, Steven A., and Henry A. Pitt. ‘‘Biliary Tract.’’ In
Sabiston Textbook of Surgery, edited by Courtney
Townsend, Jr., 16th ed. Philadelphia: W.B. Saunders
Company, 2001, pp. 1076-1111.
GALE ENCYCLOPEDIA OF MEDICINE

National Cancer Institute Cancer Trials web site. <http://
cancertrials.nci.nih.gov/system>. <http://
www.cancertrials.com>.

Kevin O. Hwang, MD

Gallbladder disease see Cholecystitis

Gallbladder nuclear
medicine scan
Definition
A nuclear medicine scan of the gallbladder is used
to produce a set of images that look like x rays. The
procedure uses a small amount of radioactive dye
which is injected into the body. The dye accumulates
in the organ, in this case, the gallbladder. A special
camera called a scintillation or gamma camera
produces images based on how the dye travels through
the system and how the radiation is absorbed by the
tissues. The procedure is also called cholescintigraphy
or a hepatobiliary scan.

Gallbladder disease, gallstones, cancer, or other
abnormalities can cause pain and other symptoms. A
gallbladder condition might be suspected if a patient has
chronic or occasional pain in the upper right side of the
abdomen. The pain may be stabbing and intense with
sudden onset or it may be more of a dull, occasional
ache. Loss of appetite, nausea and vomiting can also
occur. Fever may indicate the presence of infection.
Jaundice, a yellowing of the skin and whites of the eyes,
may also indicate that the gallbladder is involved.
A gallbladder nuclear medicine scan may be used
to diagnose gallstones, blockage of the bile duct or
other abnormalities, and to assess gallbladder functioning and inflammation (cholecystitis). The scan is
usually performed in a hospital or clinical radiology
department. The patient lies on an examination table
while a small amount of radioactive dye is injected into
a vein in the arm. This dye circulates through the
blood and collects in the gallbladder. As the dye
moves through the gallbladder, a series of pictures is
taken using a special camera called a scintillation or
gamma camera. This procedure produces images that
look like x rays. The test usually takes one to two
hours to complete, but can last up to four hours.
The results of the scan are read by a radiologist, a
doctor specializing in x rays and other types of scanning
techniques. A report is sent, usually within 24 hours, to
the doctor who will discuss the results with the patient.

Purpose
A nuclear medicine scan can be used to diagnose
disease and to find abnormalities in a body organ. A
gallbladder scan can detect gallstones, tumors, or
defects of the gallbladder. It can also be used to
diagnose blockages of the bile duct that leads from
the gallbladder to the small intestine. Unlike ultrasound, a gallbladder nuclear medicine scan can assess
gallbladder function.

Preparation
The patient may be required to withhold food and
liquids for up to eight hours before the scan.

Aftercare
No special care is required after the procedure.
Once the scan is complete, the patient can return to
normal activities.

Precautions
Women who are pregnant or breastfeeding
should tell their doctors before a scan is performed.
Some medications or even eating a high fat meal
before the procedure can interfere with the results
of the scan.

Description
The gallbladder is a small pear-shaped sac located
under the liver. The liver produces bile, a yellowishgreen mixture of salts, acids, and other chemicals, that
are stored in the gallbladder. Bile is secreted into the
small intestine to help the body digest fats from foods.
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Nuclear medicine scans use a very small amount
of radioactive material, and the risk of radiation is
minimal. Very rarely, a patient may have a reaction
to the dye material used.

Normal results
A normal scan shows a gallbladder without gallstones. There will be no evidence of growths or
tumors, and no signs of infection or swelling. The
normal gallbladder fills with bile and secretes it
through the bile duct without blockages.
1539

Gallbladder nuclear medicine scan

OTHER

Gallbladder x rays

KEY TERMS
Cholecystitis—Inflammation of the gallbladder.
Cholescintigraphy—Another term for a gallbladder
nuclear medicine scan.
Hepatobiliary scan—Another term for a gallbladder nuclear medicine scan.
Scintillation or gamma camera—A camera, somewhat like an x-ray machine, used to photograph
internal organs after the patient has been injected
with a radioactive material.

Abnormal results
An abnormal scan may show abnormal gallbladder emptying (suggesting gallbladder dysfunction or
inflammation), or gallstones in the gallbladder or in
the bile duct. The presence of tumors, growths or other
types of blockages of the duct or the gallbladder itself
could also appear on an abnormal scan.
Resources
OTHER

‘‘Gallbladder Scan, Radioisotope.’’ Infonet. <http://
infonet.med.cornell.edu>.
‘‘Nuclear Medicine.’’ Washington Radiology Associates
Page. <http://www.wrapc.com>.

Altha Roberts Edgren

the presence of many, many gallstones. It can also help
determine whether the cystic duct is clear, prior to
surgical procedures such as lithotripsy. OCG may
also be used to evaluate gallbladder disease that
doesn’t involve gallstones, such as adenomyomatosis
of the gallbladder or cholesterolosis of the gallbladder.

Purpose
This test, also known as an oral cholecystogram or
OCG, is usually ordered to help physicians diagnose
disorders of the gallbladder, such as gallstones and
tumors, which show up as solid dark structures. It
is performed to help in the investigation of patients
with upper abdominal pain. The test also measures
gallbladder function, as the failure of the organ to
visualize can signify a non-functioning or diseased
gallbladder. The gallbladder may also not visualize if
the bilirubin level is over 4 and the study should not be
performed under these circumstances.

Precautions
Your physician must be notified if you are pregnant or allergic to iodine. Patients with a history of
severe kidney damage, have an increased risk of injury
or side effects from the procedure. In those cases, ultrasound is commonly used instead of the x-ray examination. Some people experience side effects from the
contrast material (dye tablets), especially diarrhea.
During preparation for the test, patients should not
use any laxatives. Diabetics should discuss the need
for any adjustment in medication with their physician.

Gallbladder surgery see Cholecystectomy
Description

Gallbladder x rays
Definition
This is an x-ray exam of the gallbladder (GB), a
sac-like organ that stores bile that is located under the
liver. The study involves taking tablets containing
dye (contrast) which outline any abnormalities when
x rays are taken the following day. The test was
once the standard for diagnosing diseases of the GB
such as gallstones, but is used less frequently now. This
is due to advances in diagnostic ultrasound, which
is quick, accurate and doesn’t involve exposure to
ionizing radiation. When functional parameters of
the gallbladder need to be demonstrated, scintigraphy
is now the study of choice. OCG, however, can be
useful when a gallbladder is contracted down due to
1540

The exam is performed in the radiology department. The night before the test, patients swallow six
tablets (one at a time) that contain the contrast (x-ray
dye). The following day at the hospital, the radiologist
examines the gallbladder with a fluoroscope (a special
x ray that projects the image onto a video monitor).
Sometimes, patients are then asked to drink a highfat
formula that will cause the gallbladder to contract
and release bile. X rays will then be taken at various
intervals. There is no discomfort from the test. If the
gallbladder is not seen, the patient may be asked to
return the following day for x rays.

Preparation
The day before the test patients are instructed to
eat a high fat lunch (eggs, butter, milk, salad oils, or
fatty meats), and a fat-free meal (fruits, vegetables,
GALE ENCYCLOPEDIA OF MEDICINE

Bile—A yellow-green liquid produced by the liver,
which is released through the bile ducts into the
small intestines to help digest fat.
Bilirubin—A reddish-yellow pigment formed from
the destruction of red blood cells, and metabolized
by the liver. Levels of bilirubin in the blood increase
in patients with liver disease or blockage of the
bile ducts.
Ultrasound—A non-invasive procedure based on
changes in sound waves of a frequency that cannot
be heard, but respond to changes in tissue composition. It requires no preparation and no radiation
occurs; it has become the ‘‘gold standard’’ for
diagnosis of stones in the gallbladder, but is less
accurate in diagnosing stones in the bile ducts.
Gallstones as small as 2 mm can be identified.

OTHER

‘‘Gall Bladder Exam.’’ Harvard Medical School. <http://
www.bih.harvard.edu/radiology/Modalities/Xray/
xraysSubdivsf/gallbl.html>.
‘‘Gallstones.’’ National Institutes of Health. <http://
www.niddk.nih.gov/health/digest/pubs/gallstns/
gallstns.htm>.
‘‘Oral cholecystogram.’’ Healthanswers.com. <http://
www.healthanswers.com/database/ami/converted/
003821.html>.

Rosalyn Carson-DeWitt, MD

Gallium scan of the body
Definition

bread, tea or coffee, and only lean meat) in the evening.
Two hours after the evening meal, six tablets containing
the contrast medium, are taken, one a time. After that,
no food or fluid is permitted until after the test.

Aftercare
No special care is required after the study.

Risks
There is a small chance of an allergic reaction to
the contrast material. In addition, there is low radiation exposure. X rays are monitored and regulated to
provide the minimum amount of radiation exposure
needed to produce the image. Most experts feel that
the risk is low compared with the benefits. Pregnant
women and children are more sensitive to the risks of
x rays, and the risk versus benefits should be discussed
with the treating physician.

A gallium scan of the body is a nuclear medicine
test that is conducted using a camera that detects
gallium, a form of radionuclide, or radioactive chemical substance.

Purpose
Most gallium scans are ordered to detect cancerous tumors, infections, or areas of inflammation in the
body. Gallium is known to accumulate in inflamed,
infected, or cancerous tissues. The scans are used to
determine whether a patient with an unexplained fever
has an infection and the site of the infection, if present.
Gallium scans also may be used to evaluate cancer
following chemotherapy or radiation therapy.

Precautions
Children and women who are pregnant or breastfeeding are only given gallium scans if the potential
diagnostic benefits will outweigh the risks.

Normal results
The x ray will show normal structures for the age
of the patient. The gallbladder should visualize, and be
free of any solid structures, such as stones, polyps, etc.

Abnormal results
Abnormal results may show gallstones, tumors,
or cholesterol polyps (a tumor growing from the lining
that is usually noncancerous). Typically stones will
‘‘float’’ or move around as the patient changes
position, whereas tumors will stay in the same place.
GALE ENCYCLOPEDIA OF MEDICINE

Description
The patient will usually be asked to come to the
testing facility 24–48 hours before the procedure to
receive the injection of gallium. Sometimes, the injection will be given only four to six hours before the
study or as long as 72 hours before the procedure. The
timeframe is based on the area or organs of the body
being studied.
For the study itself the patient lies very still for
approximately 30–60 minutes. A camera is moved
1541

Gallium scan of the body

Resources

KEY TERMS

Gallium scan of the body

across the patient’s body to detect and capture
images of concentrations of the gallium. The camera
picks up signals from any accumulated areas of the
radionuclide. In most cases, the patient is lying down
throughout the procedure. Back (posterior) and front
(anterior) views will usually be taken, and sometimes a
side (lateral) view is used. The camera may occasionally touch the patient’s skin, but will not cause any
discomfort. A clicking noise may be heard throughout
the procedure; this is only the sound of the scanner
registering radiation.

Preparation
The intravenous injection of gallium is done in
a separate appointment prior to the procedure.
Generally, no special dietary requirements are necessary. Sometimes the physician will ask that the patient
have light or clear meals within a day or less of the
procedure. Many patients will be given laxatives or an
enema prior to the scan to eliminate any residual
gallium from the bowels.

Gallium scan highlighting the thyroid
Researchers. Reproduced by permission.)

gland.

(Photo

Aftercare
There is generally no aftercare required following
a gallium scan. However, women who are breastfeeding who have a scan will be cautioned against
breastfeeding for four weeks following the exam.

Risks
There is a minimal risk of exposure to radiation
from the gallium injection, but the exposure from one
gallium scan is generally less than exposure from
x rays.

Normal results
A radiologist trained in nuclear medicine or a
nuclear medicine specialist will interpret the exam
results and compare them to other diagnostic tests. It
is normal for gallium to accumulate in the liver, spleen,
bones, breast tissue, and large bowel.

Abnormal results
An abnormal concentration of gallium in areas
other than those where it normally concentrates may
indicate the presence of disease. Concentrations may
be due to inflammation, infection, or the presence of
tumor tissue. Often, additional tests are required to
determine if the tumors are malignant (cancerous) or
benign.
1542

KEY TERMS
Benign—Not cancerous. Benign tumors are not
considered immediate threats, but may still require
some form of treatment.
Gallium—A form of radionuclide that is used to
help locate tumors and inflammation (specifically
referred to as GA67 citrate).
Malignant—This term, usually used to describe a
tumor, means cancerous, becoming worse and
possibly growing.
Nuclear medicine—A subspecialty of radiology
used to show the function and anatomy of body
organs. Very small amounts of radioactive substances, or tracers, are detected with a special camera as they accumulate in certain organs and tissues.
Radionuclide—A chemical substance, called an
isotope, that exhibits radioactivity. A gamma camera, used in nuclear medicine procedures, will pick
up the radioactive signals as the substance gathers
in an organ or tissue. They are sometimes referred
to as tracers.

Even though gallium normally concentrates in
organs such as the liver or spleen, abnormally high
concentrations will suggest certain diseases and
GALE ENCYCLOPEDIA OF MEDICINE

based on the concentration of three chemicals, not
just one–bile acids, phospholipids, and cholesterol. If
the chemicals are out of balance, one or the other will
not remain in solution. Certain people, in particular
the Pima tribe of Native Americans in Arizona,
have a genetic predisposition to forming gallstones.
Scandinavians also have a higher than average incidence of this disease. Dietary fat and cholesterol are
also implicated in their formation. Overweight women
in their middle years constitute the vast majority of
patients with gallstones in every group.

Resources

As the bile crystals aggregate to form stones, they
move about, eventually occluding the outlet and
preventing the gallbladder from emptying. This creates
symptoms. It also results in irritation, inflammation,
and sometimes infection of the gallbladder. The pattern
is usually one of intermittent obstruction due to
stones moving in and out of the way. All the while
the gallbladder is becoming more scarred. Sometimes
infection fills it with pus–a serious complication.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (404) 320-3333. <http://www.cancer.org>.
American College of Nuclear Medicine. PO Box 175,
Landisville, PA 31906. (717) 898-6006.
American Liver Foundation. 1425 Pompton Avenue, Cedar
Grove NJ 07009. (800) GO LIVER (465-4837).
<http://www.liverfoundation.org>.
Society of Nuclear Medicine. 1850 Samuel Morse Drive,
Reston, VA 10016. (703) 708-9000. <http://
www.snm.org>.
OTHER

‘‘A Patient’s Guide to Nuclear Medicine.’’ University of Iowa
Virtual Hospital. July 2, 2001. <http://www.vh.org/
Patients/IHB/Rad/NucMed/PatGuideNucMed/
PatGuideNucMed.html>.

Teresa Odle

Gallstone removal
Definition
Also known as cholelithotomy, gallstone removal
is the medical procedure that rids the gallbladder of
calculus buildup.

Purpose
The gallbladder is not a vital organ. Its function
is to store bile, concentrate it, and release it during
digestion. Bile is supposed to retain all of its chemicals
in solution, but commonly one of them crystallizes and
forms sand, gravel, and finally stones.
The chemistry of gallstones is complex and interesting. Like too much sugar in solution, chemicals in
bile will form crystals as the gallbladder draws water
out of the bile. The solubility of these chemicals is
GALE ENCYCLOPEDIA OF MEDICINE

On occasion a stone will travel down the cystic duct
into the common bile duct and get stuck there. This will
back bile up into the liver as well as the gallbladder. If
the stone sticks at the Ampulla of Vater, the pancreas
will also be plugged and will develop pancreatitis. These
stones can cause a lot of trouble.
Bile is composed of several waste products of
metabolism, all of which are supposed to remain in
liquid form. The complex chemistry of the liver depends
on many chemical processes, which depend in turn
upon the chemicals in the diet and the genes that direct
those processes. There are greater variations in the
output of chemical waste products than there is allowance for their cohabitation in the bile. Incompatible
mixes result in the formation of solids.
Gallstones will cause the sudden onset of pain in
the upper abdomen. Pain will last for 30 minutes to
several hours. Pain may move to the right shoulder
blade. Nausea with or without vomiting may accompany the pain.

Precautions
Individuals suffering from sickle cell anemia,
children, and patients with large stones may seek
other treatments.

Description
Laparoscopic cholecystectomy
Surgery to remove the entire gallbladder with all
its stones is usually the best treatment, provided the
1543

Gallstone removal

conditions. For example, Hodgkin’s or nonHodgkin’s lymphoma may be diagnosed or staged if
there is abnormal gallium activity in the lymph nodes.
After a patient receives cancer treatment, such as
radiation therapy or chemotherapy, a gallium scan
may help to find new or recurring tumors or to record
regression of a treated tumor. Physicians can narrow
causes of liver problems by noting abnormal gallium
activity in the liver. Gallium scans also may be used to
diagnose lung diseases or a disease called sarcoidosis,
in the chest.

Gallstone removal

Gallbladder

Cystic duct

Gallbladder
Liver

Gallstones

Pyloric sphincter

Common bile duct
Duodenum

Pancreas

Gallstone removal, also known as cholelithotomy, usually involves the surgical removal of the entire gallbladder, but in recent
years the procedure done by laparoscopy has resulted in smaller surgical incisions and faster recovery time. (Illustration by
Electronic Illustrators Group.)

patient is able to tolerate the procedure. Over the past
decade, a new technique of removing the gallbladder
using a laparoscope has resulted in quicker recovery
and much smaller surgical incisions than the six-inch
gash under the right ribs that used to be standard. Not
everyone is a candidate for this approach.
If a stone is lodged in the bile ducts, additional
surgery must be done to remove it. After surgery, the
surgeon will ordinarily leave in a drain to collect bile
until the system is healed. The drain can also be used to
inject contrast material and take x rays during or after
surgery.
Endoscopic retrograde cholangiopancreatoscopy
(ERCP)
A procedure called endoscopic retrograde cholangiopancreatoscopy (ERCP) allows the removal of
some bile duct stones through the mouth, throat,
esophagus, stomach, duodenum, and biliary system
1544

without the need for surgical incisions. ERCP can
also be used to inject contrast agents into the biliary
system, providing superbly detailed pictures.
Cholelithotomy
Rare circumstances require different techniques.
Patients too ill for a complete cholecystectomy
(removal of the gallbladder), sometimes only
the stones are removed, a procedure called cholelithotomy. But that does not cure the problem. The liver will
go on making faulty bile, and stones will reform,
unless the composition of the bile is altered.
Ursodeoxycholic acid
For patients who cannot receive the laparoscopic
procedure, there is also a nonsurgical treatment in
which ursodeoxycholic acid is used to dissolve the
gallstones. Extracorporeal shock-wave lithotripsy has
also been successfully used to break up gallstones.
GALE ENCYCLOPEDIA OF MEDICINE

Cholecystectomy—Surgical removal of the gallbladder.
Cholelithotomy—Surgical incision into the gallbladder to remove stones.
Contrast agent—A substance that causes shadows
on x rays (or other images of the body).
Endoscope—One of several instruments designed
to enter body cavities. They combine viewing and
operating capabilities.
Jaundice—A yellow color of the skin and eyes due
to excess bile that is not removed by the liver.
Laparoscopy—Surgery through pencil-sized viewing instruments and tools so that incisions need be
less than half an inch long.

During the procedure, high-amplitude sound waves
target the stones, slowly breaking them up.

Preparation
There are a number of imaging studies that identify
gallbladder disease, but most gallstones will not show
up on conventional x rays. That requires contrast
agents given by mouth that are excreted into the bile.
Ultrasound is very useful and can be enhanced by doing
it through an endoscope in the stomach. CT (computed
tomography scans) and MRI (magnetic resonance
imaging) scanning are not used routinely but are helpful
in detecting common duct stones and complications.

Aftercare
Without a gallbladder, stones rarely reform.
Patients who have continued symptoms after their
gallbladder is removed may need an ERCP to detect
residual stones or damage to the bile ducts caused by
the stones before they were removed. Once in a while
the Ampulla of Vater is too tight for bile to flow
through and causes symptoms until it is opened up.
Resources
BOOKS

Bilhartz, Lyman E., and Jay D. Horton. ‘‘Gallstone
Disease and Its Complications.’’ In Sleisenger &
Fordtran’s Gastrointestinal and Liver Disease, edited
by Mark Feldman, et al. Philadelphia: W. B. Saunders
Co., 1998.

J. Ricker Polsdorfer, MD
GALE ENCYCLOPEDIA OF MEDICINE

Gallstones

KEY TERMS

Gallstones
Definition
A gallstone is a solid crystal deposit that forms in
the gallbladder, which is a pear-shaped organ that
stores bile salts until they are needed to help digest
fatty foods. Gallstones can migrate to other parts
of the digestive tract and cause severe pain with
life-threatening complications.

Description
Gallstones vary in size and chemical structure.
A gallstone may be as tiny as a grain of sand or as
large as a golf ball. Eighty percent of gallstones are
composed of cholesterol. They are formed when the
liver produces more cholesterol than digestive
juices can liquefy. The remaining 20% of gallstones
are composed of calcium and an orange-yellow
waste product called bilirubin. Bilirubin gives
urine its characteristic color and sometimes causes
jaundice.
Gallstones are the most common of all gallbladder problems. They are responsible for 90% of gallbladder and bile duct disease, and are the fifth most
common reason for hospitalization of adults in the
United States. Gallstones usually develop in adults
between the ages of 20 and 50; about 20% of patients
with gallstones are over 40. The risk of developing
gallstones increases with age–at least 20% of people
over 60 have a single large stone or as many as several
thousand smaller ones. The gender ratio of gallstone
patients changes with age. Young women are between
two and six times more likely to develop gallstones
than men in the same age group. In patients over 50,
the condition affects men and women with equal frequency. Native Americans develop gallstones more
often than any other segment of the population;
Mexican-Americans have the second-highest incidence of this disease.
Definitions
Gallstones can cause several different disorders.
Cholelithiasis is defined as the presence of gallstones
within the gallbladder itself. Choledocholithiasis is the
presence of gallstones within the common bile duct
that leads into the first portion of the small intestine
(the duodenum). The stones in the duct may have been
formed inside it or carried there from the gallbladder.
These gallstones prevent bile from flowing into the
duodenum. Ten percent of patients with gallstones
1545

Gallstones

have choledocholithiasis, which is sometimes called
common-duct stones. Patients who don’t develop
infection usually recover completely from this
disorder.
Cholecystitis is a disorder marked by inflammation of the gallbladder. It is usually caused by the
passage of a stone from the gallbladder into the cystic
duct, which is a tube that connects the gallbladder to
the common bile duct. In 5–10% of cases, however,
cholecystitis develops in the absence of gallstones.
This form of the disorder is called acalculous cholecystitis. Cholecystitis causes painful enlargement of
the gallbladder and is responsible for 10–25% of all
gallbladder surgery. Chronic cholecystitis is most
common in the elderly. The acute form is most likely
to occur in middle-aged adults.
Cholesterolosis or cholesterol polyps is characterized by deposits of cholesterol crystals in the lining of
the gallbladder. This condition may be caused by high
levels of cholesterol or inadequate quantities of bile
salts, and is usually treated by surgery.
Gallstone ileus, which results from a gallstone’s
blocking the entrance to the large intestine, is most
common in elderly people. Surgery usually cures this
condition.
Narrowing (stricture) of the common bile duct
develops in as many as 5% of patients whose gallbladders have been surgically removed. This condition is characterized by inability to digest fatty foods
and by abdominal pain, which sometimes occurs in
spasms. Patients with stricture of the common bile
duct are likely to recover after appropriate surgical
treatment.

Causes and symptoms
Gallstones are caused by an alteration in the
chemical composition of bile. Bile is a digestive fluid
that helps the body absorb fat. Gallstones tend to run
in families. In addition, high levels of estrogen, insulin,
or cholesterol can increase a person’s risk of developing them.
Pregnancy or the use of birth control pills can
slow down gallbladder activity and increase the
risk of gallstones. So can diabetes, pancreatitis, and
celiac disease. Other factors influencing gallstone
formation are:


infection



obesity



intestinal disorders

1546



coronary artery disease or other recent illness



multiple pregnancies



a high-fat, low-fiber diet



smoking



heavy drinking



rapid weight loss

Gallbladder attacks usually follow a meal of rich,
high-fat foods. The attacks often occur in the middle
of the night, sometimes waking the patient with
intense pain that ends in a visit to the emergency
room. The pain of a gallbladder attack begins in the
abdomen and may radiate to the chest, back, or the
area between the shoulders. Other symptoms of
gallstones include:


inability to digest fatty foods



low-grade fever



chills and sweating



nausea and vomiting



indigestion



gas



belching.



clay-colored bowel movements

Diagnosis
Gallstones may be diagnosed by a family doctor,
a specialist in digestive problems (a gastroenterologist), or a specialist in internal medicine. The doctor
will first examine the patient’s skin for signs of jaundice and feel (palpate) the abdomen for soreness or
swelling. After the basic physical examination, the
doctor will order blood counts or blood chemistry
tests to detect evidence of bile duct obstruction and
to rule out other illnesses that cause fever and pain,
including stomach ulcers, appendicitis, and heart
attacks.
More sophisticated procedures used to diagnose
gallstones include:


Ultrasound imaging. Ultrasound has an accuracy
rate of 96%.



Cholecystography (cholecystogram, gallbladder series, gallbladder x ray). This type of study shows how
the gallbladder contracts after the patient has eaten a
high-fat meal.



Fluoroscopy. This imaging technique allows the doctor to distinguish between jaundice caused by pancreatic cancer and jaundice caused by gallbladder or
bile duct disorders.
GALE ENCYCLOPEDIA OF MEDICINE

Gallstones

Stones

Common
bile duct

Gallbladder

Gallstones form in the gallbladder but can migrate to other parts of the body via the bile duct. (Illustration by Argosy Inc.)





Endoscopy (ERCP). ERCP uses a special dye to outline the pancreatic and common bile ducts and locate
the position of the gallstones.
Radioisotopic scan. This technique reveals blockage
of the cystic duct.

Treatment
Watchful waiting
One-third of all patients with gallstones never experience a second attack. For this reason many doctors advise
watchful waiting after the first episode. Reducing the
amount of fat in the diet or following a sensible plan of
gradual weight loss may be the only treatments required
for occasional mild attacks. A patient diagnosed with
gallstones may be able to manage more troublesome
episodes by:
GALE ENCYCLOPEDIA OF MEDICINE



applying heat to the affected area



resting and taking occasional sips of water



using non-prescription forms of acetaminophen
(Tylenol or Anacin-3)

A doctor should be notified if pain intensifies or
lasts for more than three hours; if the patient’s fever
rises above 101 8F (38.3 8C); or if the skin or whites of
the eyes turn yellow.
Surgery
Surgical removal of the gallbladder (cholecystectomy) is the most common conventional treatment for
recurrent attacks. Laparoscopic surgery, the technique most widely used, is a safe, effective procedure
that involves less pain and a shorter recovery period
than traditional open surgery. In this technique, the
1547

Gallstones

doctor makes a small cut (incision) in the patient’s
abdomen and removes the gallbladder through a
long tube called a laparoscope.
Nonsurgical approaches
LITHOTRIPSY. Shock wave therapy (lithotripsy)
uses high-frequency sound waves to break up the gallstones. The patient can then take bile salts to dissolve
the fragments. Bile salt tablets are sometimes prescribed without lithotripsy to dissolve stones composed of cholesterol by raising the level of bile acids
in the gallbladder. This approach requires long-term
treatment, since it may take months or years for this
method to dissolve a sizeable stone.
CONTACT DISSOLUTION. Contact dissolution can
destroy gallstones in a matter of hours. This minimally
invasive procedure involves using a tube (catheter)
inserted into the abdomen to inject medication directly
into the gallbladder.

Alternative treatment
Alternative therapies, like non-surgical treatments, may provide temporary relief of gallstone
symptoms. Alternative approaches to the symptoms
of gallbladder disorders include homeopathy, Chinese
traditional herbal medicine, and acupuncture. Dietary
changes may also help relieve the symptoms of gallstones. Since gallstones seem to develop more often in
people who are obese, eating a balanced diet, exercising, and losing weight may help keep gallstones from
forming.

KEY TERMS
Acalculous cholecystitis—Inflammation of the
gallbladder that occurs without the presence of
gallstones.
Bilirubin—A reddish-yellow waste product produced by the liver that colors urine and is involved
in the formation of some gallstones.
Celiac disease—Inability to digest wheat protein
(gluten), which causes weight loss, lack of energy,
and pale, foul-smelling stools.
Cholecystectomy—Surgical removal of the
gallbladder.
Cholecystitis—Inflammation of the gallbladder.
Choledocholithiasis—The presence of gallstones
within the common bile duct.
Cholelithiasis—The presence of gallstones within
the gallbladder.
Cholesterolosis—Cholesterol crystals or deposits
in the lining of the gallbladder.
Common bile duct—The passage through which
bile travels from the cystic duct to the small
intestine.
Gallstone ileus—Obstruction of the large intestine
caused by a gallstone that has blocked the intestinal
opening.
Lithotripsy—A nonsurgical technique for removing
gallstones by breaking them apart with highfrequency sound waves.

Prognosis
Forty percent of all patients with gallstones have
‘‘silent gallstones’’ that produce no symptoms. Silent
stones, discovered only when their presence is indicated by tests performed to diagnose other symptoms,
do not require treatment.
Gallstone problems that require treatment can be
surgically corrected. Although most patients recover,
some develop infections that must be treated with
antibiotics.
In rare instances, severe inflammation can cause the
gallbladder to burst. The resulting infection can be fatal.

Prevention
The best way to prevent gallstones is to minimize
risk factors. In addition, a 1998 study suggests that
vigorous exercise may lower a man’s risk of developing gallstones by as much as 28%. The researchers
1548

have not yet determined whether physical activity
benefits women to the same extent.
Resources
ORGANIZATIONS

National Digestive Diseases Clearinghouse (NDDIC).
2 Information Way.
National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK). Building 31, Room 9A04, 31
Center Drive, MSC 2560, Bethesda, MD 208792-2560.
(301) 496-3583. <http://www.niddk.nih.gov>.

Maureen Haggerty

Gamete intrafallopian transfer see Infertility
therapies
Gamma-glutamyl transferase test see Liver
function tests
GALE ENCYCLOPEDIA OF MEDICINE

Definition

Hepatitis—Inflammation of the liver caused by a
virus, chemical or drugs. There are several different
types of hepatitis, including the most common
forms: hepatitis A, hepatitis B, and hepatitis C.

Gammaglobulin is a type of protein found in the
blood. When gammaglobulins are extracted from the
blood of many people and combined, they can be used
to prevent or treat infections.

Immune system—The body’s natural defenses
against disease and infection.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.

Purpose
This medicine is used to treat or prevent diseases
that occur when the body’s own immune system is not
effective against the disease. When disease-causing
agents enter the body, they normally trigger the
production of antibodies, proteins that circulate in
the blood and help fight the disease. Gammaglobulin
contains some of these antibodies. When gammaglobulins are taken from the blood of people who
have recovered from diseases such as chickenpox or
hepatitis, they can be given to other people to make
them temporarily immune to those diseases. With
hepatitis, for example, this is done when someone
who has not been vaccinated against hepatitis is
exposed to the disease.

Description
Gammaglobulin, also known as immunoglobulin,
immune serum globulin or serum therapy, is injected
either into a vein or into a muscle. When injected into a
vein, it produces results more quickly than when
injected into a muscle.

Recommended dosage
Doses are different for different people and
depend on the person’s body weight and the condition
for which he or she is being treated.

Precautions
Anyone who has had unusual reactions to
gammaglobulin in the past should let his or her physician know before taking the drugs again. The physician should also be told about any allergies to foods,
dyes, preservatives, or other substances.
People who have certain medical conditions may
have problems if they take gammaglobulins. For
example:


Gammaglobulins may worsen heart problems or
deficiencies of immunoglobin A (IgA, a type of
antibody)

GALE ENCYCLOPEDIA OF MEDICINE



Certain patients with low levels of gammaglobulins
in the blood (conditions called agammaglobulinemia and hypogammaglobulinemia) may be
more likely to have side effects when they take
gammaglobulin.

Side effects
Minor side effects such as headache, backache,
joint or muscle pain, and a general feeling of illness
usually go away as the body adjusts to this medicine.
These problems do not need medical attention unless
they continue.
Other side effects, such as breathing problems or
a fast or pounding heartbeat, should be brought to a
physician’s attention as soon as possible.
Anyone who shows the following signs of
overdose should check with a physician immediately:


unusual tiredness or weakness



dizziness



nausea



vomiting



fever



chills



tightness in the chest



red face



sweating

Interactions
Anyone who takes gammaglobulin should let
the physician know all other medicines he or she is
taking and should ask whether interactions with
gammaglobulin could interfere with treatment.
Nancy Ross-Flanigan
1549

Gammaglobulin

KEY TERMS

Gammaglobulin

Ganglion

Ganglion

Ganglion
Definition
A ganglion is a small, usually hard bump above a
tendon or in the capsule that encloses a joint. A ganglion is also called a synovial hernia or synovial cyst.

Description
Lunate bone

A ganglion is a non-cancerous cyst filled with a
thick, jelly-like fluid. Ganglions can develop on or
beneath the surface of the skin and usually occur
between the ages of 20 and 40.
Most ganglions develop on the hand or wrist. This
condition is common in people who bowl or who play
handball, raquetball, squash, or tennis. Runners and
athletes who jump, ski, or play contact sports often
develop foot ganglions.

Causes and symptoms
Mild sprains or other repeated injuries can irritate
and tear the thin membrane covering a tendon, causing
fluid to leak into a sac that swells and forms a ganglion.
Ganglions are usually painless, but range of
motion may be impaired. Flexing or bending the
affected area can cause discomfort, as can continuing
to perform the activity that caused the condition.
Cysts on the surface of the skin usually develop
slowly but may result from injury or severe strain. An
internal ganglion can cause soreness or a dull, aching
sensation, but the mass cannot always be felt.
Symptoms sometimes become evident only when the
cyst causes pressure on a nerve or outgrows the membrane surrounding it.

Diagnosis
Diagnosis is usually made through physical examination as well as such imaging studies as x ray, ultrasound, and magnetic resonance imaging (MRI). Fluid
may be withdrawn from the cyst and evaluated.

Treatment
Some ganglions disappear without treatment, and
some reappear despite treatment.
Acetaminophen (Tylenol) or other over-the-counter analgesics can be used to control mild pain.
Steroids or local anesthetics may be injected into
cysts that cause severe pain or other troublesome
1550

Scaphoid bone

A ganglion is a non-cancerous cyst filled with a thick, jellylike fluid. Ganglions can develop on or beneath the surface of
the skin, most likely on the hand or wrist, although runners
and skiers often develop them on the foot. (Illustration by
Electronic Illustrators Group.)

symptoms. Surgery performed in a hospital operating
room or an outpatient facility, is the only treatment
guaranteed to remove a ganglion. The condition can
recur if the entire cyst is not removed.
A doctor should be notified if the surgical site
drains, bleeds, or becomes


inflamed



painful



swollen or if the patient feels ill or develops:



head or muscle aches



dizziness



fever following surgery

The patient may bathe or shower as usual, but
should keep the surgical site dry and covered with a
bandage for two or three days after the operation.
Patients may resume normal activities as soon as
they feel comfortable doing so.

Prognosis
Possible complications include excessive postoperative bleeding and infection of the surgical site.
Calcification, or hardening, of the ganglion is rare.
GALE ENCYCLOPEDIA OF MEDICINE

Exercises that increase muscle strength and flexibility can prevent ganglions. Warming and cooling
down before and after workouts may also decrease
the rate of developing ganglions.
Resources
OTHER

‘‘Foot Ganglion.’’ ThriveOnline. May 25, 1998. <http://
thriveonline.oxygen.com>.
‘‘Hand or Wrist Ganglion.’’ ThriveOnline. May 25, 1998.
<http://thriveonline.oxygen.com>.

Maureen Haggerty

Gangrene
Definition
Gangrene is the term used to describe the decay or
death of an organ or tissue caused by a lack of blood
supply. It is a complication resulting from infectious
or inflammatory processes, injury, or degenerative
changes associated with chronic diseases, such as diabetes mellitus.

Description
Gangrene may be caused by a variety of chronic
diseases and post-traumatic, post-surgical, and spontaneous causes. There are three major types of gangrene: dry, moist, and gas (a type of moist gangrene).
Dry gangrene is a condition that results when one
or more arteries become obstructed. In this type of
gangrene, the tissue slowly dies, due to receiving little
or no blood supply, but does not become infected. The
affected area becomes cold and black, begins to dry
out and wither, and eventually drops off over a period
of weeks or months. Dry gangrene is most common in
persons with advanced blockages of the arteries (arteriosclerosis) resulting from diabetes.
Moist gangrene may occur in the toes, feet, or legs
after a crushing injury or as a result of some other
factor that causes blood flow to the area to suddenly
stop. When blood flow ceases, bacteria begin to invade
the muscle and thrive, multiplying quickly without
interference from the body’s immune system.
Gas gangrene, also called myonecrosis, is a type of
moist gangrene that is commonly caused by bacterial
GALE ENCYCLOPEDIA OF MEDICINE

infection with Clostridium welchii, Cl. perfringes,
Cl. septicum, Cl. novyi, Cl. histolyticum, Cl. sporogenes, or other species that are capable of thriving
under conditions where there is little oxygen (anaerobic). Once present in tissue, these bacteria produce
gasses and poisonous toxins as they grow. Normally
inhabiting the gastrointestinal, respiratory, and
female genital tract, they often infect thigh amputation
wounds, especially in those individuals who have lost
control of their bowel functions (incontinence).
Gangrene, incontinence, and debility often are combined in patients with diabetes, and it is in the amputation stump of diabetic patients that gas gangrene is
often found to occur.
Other causative organisms for moist gangrene include various bacterial strains, including
Streptococcus and Staphylococcus. A serious, but
rare form of infection with Group A Streptococcus
can impede blood flow and, if untreated, can progress
to synergistic gangrene, more commonly called necrotizing fasciitis, or infection of the skin and tissues
directly beneath the skin.
Chronic diseases, such as diabetes mellitus, arteriosclerosis, or diseases affecting the blood vessels, such
as Buerger’s disease or Raynaud’s disease, can cause
gangrene. Post-traumatic causes of gangrene include
compound fractures, burns, and injections given under
the skin or in a muscle. Gangrene may occur following
surgery, particularly in individuals with diabetes mellitus or other long-term (chronic) disease. In addition,
gas gangrene can be also be a complication of dry
gangrene or occur spontaneously in association with
an underlying cancer.
In the United States, approximately 50% of moist
gangrene cases are the result of a severe traumatic
injury, and 40% occur following surgery. Car and
industrial accidents, crush injuries, and gunshot
wounds are the most common traumatic causes.
Because of prompt surgical management of wounds
with the removal of dead tissue, the incidence of gangrene from trauma has significantly diminished.
Surgeries involving the bile ducts or intestine are the
most frequent procedures causing gangrene.
Approximately two-thirds of cases affect the extremities, and the remaining one-third involve the abdominal wall.

Symptoms
Areas of either dry or moist gangrene are initially
characterized by a red line on the skin that marks the
border of the affected tissues. As tissues begin to die,
dry gangrene may cause some pain in the early stages
1551

Gangrene

Prevention

Gangrene

or may go unnoticed, especially in the elderly or in
those individuals with diminished sensation to the
affected area. Initially, the area becomes cold, numb,
and pale before later changing in color to brown, then
black. This dead tissue will gradually separate from
the healthy tissue and fall off.
Moist gangrene and gas gangrene are distinctly
different. Gas gangrene does not involve the skin as
much, but usually only the muscle. In moist or gas
gangrene, there is a sensation of heaviness in the
affected region that is followed by severe pain. The
pain is caused by swelling resulting from fluid or gas
accumulation in the tissues. This pain peaks, on average, between one to four days following the injury,
with a range of eight hours to several weeks. The
swollen skin may initially be blistered, red, and warm
to the touch before progressing to a bronze, brown, or
black color. In approximately 80% of cases, the
affected and surrounding tissues may produce crackling sounds (crepitus), as a result of gas bubbles accumulating under the skin. The gas may be felt beneath
the skin (palpable). In wet gangrene, the pus is foulsmelling, while in gas gangrene, there is no true pus,
just an almost ‘‘sweet’’ smelling watery discharge.
Fever, rapid heart rate, rapid breathing, altered
mental state, loss of appetite, diarrhea, vomiting, and
vascular collapse may also occur if the bacterial toxins
are allowed to spread in the bloodstream. Gas gangrene can be a life-threatening condition and should
receive prompt medical attention

Diagnosis
A diagnosis of gangrene will be based on a combination of the patient history, a physical examination,
and the results of blood and other laboratory tests. A
physician will look for a history of recent trauma,
surgery, cancer, or chronic disease. Blood tests will
be used to determine whether infection is present and
determine the extent to which an infection has spread.
A sample of drainage from a wound, or obtained
through surgical exploration, may be cultured with
oxygen (aerobic) and without oxygen (anaerobic) to
identify the microorganism causing the infection and
to aid in determining which antibiotic will be most
effective. The sample obtained from a person with
gangrene will contain few, if any, white blood cells
and, when stained (with Gram stain) and examined
under the microscope, will show the presence of purple
(Gram positive), rod-shaped bacteria.
X-ray studies and more sophisticated imaging
techniques, such as computed tomography scans (CT)
1552

A close-up of gangrene in the toes of a diabetic patient. (Photo
Researchers, Inc. Reproduced by permission.)

or magnetic resonance imaging (MRI), may be helpful
in making a diagnosis since gas accumulation and
muscle death (myonecrosis) may be visible. These
techniques, however, are not sufficient alone to provide an accurate diagnosis of gangrene.
Precise diagnosis of gas gangrene often requires
surgical exploration of the wound. During such a
procedure, the exposed muscle may appear pale,
beefy-red, or in the most advanced stages, black. If
infected, the muscle will fail to contract with stimulation, and the cut surface will not bleed.

Treatment
Gas gangrene is a medical emergency because of
the threat of the infection rapidly spreading via the
bloodstream and infecting vital organs. It requires
immediate surgery and administration of antibiotics.
Areas of dry gangrene that remain free from infection (aseptic) in the extremities are most often left to
wither and fall off. Treatments applied to the wound
externally (topically) are generally not effective without adequate blood supply to support wound healing.
Assessment by a vascular surgeon, along with x rays to
determine blood supply and circulation to the affected
area, can help determine whether surgical intervention
would be beneficial.
Once the causative organism has been identified,
moist gangrene requires the prompt initiation of intravenous, intramuscular, and/or topical broad-spectrum antibiotic therapy. In addition, the infected
tissue must be removed surgically (debridement), and
amputation of the affected extremity may be necessary. Pain medications (analgesics) are prescribed to
control discomfort. Intravenous fluids and, occasionally, blood transfusions are indicated to counteract
GALE ENCYCLOPEDIA OF MEDICINE

Although still controversial, some cases of gangrene are treated by administering oxygen under pressure greater than that of the atmosphere (hyperbaric)
to the patient in a specially designed chamber. The
theory behind using hyperbaric oxygen is that more
oxygen will become dissolved in the patient’s bloodstream, and therefore, more oxygen will be delivered
to the gangrenous areas. By providing optimal oxygenation, the body’s ability to fight off the bacterial
infection are believed to be improved, and there is
a direct toxic effect on the bacteria that thrive in an
oxygen-free environment. Some studies have shown
that the use of hyperbaric oxygen produces marked
pain relief, reduces the number of amputations
required, and reduces the extent of surgical debridement required. Patients receiving hyperbaric oxygen
treatments must be monitored closely for evidence of
oxygen toxicity. Symptoms of this toxicity include
slow heart rate, profuse sweating, ringing in the ears,
shortness of breath, nausea and vomiting, twitching of
the lips/cheeks/eyelids/nose, and convulsions.
The emotional needs of the patient must also be
met. The individual with gangrene should be offered
moral support, along with an opportunity to share
questions and concerns about changes in body
image. In addition, particularly in cases where amputation was required, physical, vocational, and rehabilitation therapy will also be required.

KEY TERMS
Aerobic—Organism that grows and thrives only in
environments containing oxygen.
Anaerobic—Organism that grows and thrives in an
oxygen-free environment.
Arteriosclerosis—Build-up of fatty plaques within
the arteries that can lead to the obstruction of blood
flow.
Aseptic—Without contamination with bacteria or
other microorganisms.
Crepitus—A crackling sound.
Gram stain—A staining procedure used to visualize
and classify bacteria. The Gram stain procedure
allows the identification of purple (Gram positive)
organisms and red (Gram negative) organisms.
Hyperbaric oxygen—Medical treatment in which
oxygen is administered in specially designed chambers, under pressures greater than that of the atmosphere, in order to treat specific medical conditions.
Incontinence—A condition characterized by the
inability to control urination or bowel functions.
Myonecrosis—The destruction or death of muscle
tissue.
Sepsis—The spreading of an infection in the
bloodstream.
Thrombosis—The formation of a blood clot in a
vein or artery that may obstruct local blood flow
or may dislodge, travel downstream, and obstruct
blood flow at a remote location.

Prognosis
Except in cases where the infection has been
allowed to spread through the blood stream, prognosis is generally favorable. Anaerobic wound infection can progress quickly from initial injury to gas
gangrene within one to two days, and the spread of
the infection in the blood stream is associated with a
20–25% mortality rate. If recognized and treated
early, however, approximately 80% of those with gas
gangrene survive, and only 15–20% require any form
of amputation. Unfortunately, the individual with dry
gangrene most often has multiple other health problems that complicate recovery, and it is usually
those other system failures that can prove fatal.

Prevention
Patients with diabetes or severe arteriosclerosis
should take particular care of their hands and feet
because of the risk of infection associated with even a
GALE ENCYCLOPEDIA OF MEDICINE

minor injury. Education about proper foot care is
vital. Diminished blood flow as a result of narrowed
vessels will not lessen the body’s defenses against
invading bacteria. Measures taken towards the reestablishment of circulation are recommended whenever
possible. Any abrasion, break in the skin, or infection
tissue should be cared for immediately. Any dying or
infected skin must be removed promptly to prevent the
spread of bacteria.
Penetrating abdominal wounds should be surgically explored and drained, any tears in the intestinal
walls closed, and antibiotic treatment begun early.
Patients undergoing elective intestinal surgery should
receive preventive antibiotic therapy. Use of antibiotics prior to and directly following surgery has been
shown to significantly reduce the rate of infection
from 20–30% to 4–8%.
1553

Gangrene

shock and replenish red blood cells and electrolytes.
Adequate hydration and nutrition are vital to wound
healing.

Gas embolism

Resources

KEY TERMS

BOOKS

Berktow, Robert, editor. The Merck Manual of Diagnosis
and Therapy. 17th ed. Rahway, NJ: Merck Research
Laboratories, 1997.
PERIODICALS

Basoglu, M., et al. ‘‘Fournier’s Gangrene: Review of Fifteen
Cases.’’ American Surgeon November 1997: 1019-1021.

Kathleen D. Wright, RN

Gas embolism
Definition
Gas embolism, also called air embolism, is the
presence of gas bubbles in the bloodstream that
obstruct circulation.

Description
Gas embolism may occur with decompression
from increased pressure; it typically occurs in ascending divers who have been breathing compressed air. If
a diver does not fully exhale upon ascent, the air in the
lungs expands as the pressure decreases, overinflating
the lungs and forcing bubbles of gas (emboli) into the
bloodstream. When gas emboli reach the arteries to
the brain, the blood blockage causes unconsciousness.
Gas embolism is second only to drowning as a cause of
death among divers.
Gas embolism may also result from trauma or
medical procedures such as catheterization and open
heart surgery that allow air into the circulatory system.

Causes and symptoms
Gas embolism occurs independent of diving depth;
it may occur in as little as 6 ft of water. It is frequently
caused by a diver holding his breath during ascent. It
may also result from an airway obstruction or other
condition that prevents a diver from fully exhaling.
The primary sign of gas embolism is immediate
loss of consciousness; it may or may not be accompanied by convulsions.

Diagnosis
Any unconscious diver should be assumed to be
the victim of gas embolism, regardless of whether
1554

Compressed air—Air that is held under pressure in
a tank to be breathed underwater by divers. A tank
of compressed air is part of a diver’s scuba (selfcontained underwater breathing apparatus) gear.
Compression—An increase in pressure from the
surrounding water that occurs with increasing diving depth.
Decompression—A decrease in pressure from the
surrounding water that occurs with decreasing diving depth.
Emboli—Plural of embolus. An embolus is something that blocks the blood flow in a blood vessel. It
may be a gas bubble, a blood clot, a fat globule, a
mass of bacteria, or other foreign body. It usually
forms somewhere else and travels through the circulatory system until it gets stuck.
Hyperbaric chamber—A sealed compartment in
which patients are exposed to controlled pressures
up to three times normal atmospheric pressure.
Hyperbaric treatment may be used to regulate blood
gases, reduce gas emboli, and provide higher levels of
oxygen more quickly in cases of severe gas poisoning.
Recompression—Restoring the elevated pressure of
the diving environment to treat gas embolism by
decreasing bubble size.

consciousness was lost during or promptly after ascent.
A doctor may also find pockets of air in the chest
around the lungs and sometimes a collapsed lung
from overinflation and rupture. Coughing up blood
or a bloody froth around the mouth are visible signs
of lung injury.

Treatment
Prompt recompression treatment in a hyperbaric
(high-pressure) chamber is necessary to deflate the gas
bubbles in the bloodstream, dissolve the gases into the
blood, and restore adequate oxygenated blood flow to
the brain and other organs. Recompression by returning the diver to deeper water will not work, and should
not be attempted. The patient should be kept lying
down and given oxygen while being transported for
recompression treatment.
Before the diver receives recompression treatment, other lifesaving efforts may be necessary. If
the diver isn’t breathing, artificial respiration
(also called mouth-to-mouth resuscitation or rescue
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The prognosis is dependent upon the promptness
of recompression treatment and the extent of the
damage caused by oxygen deprivation.

Prevention
All divers should receive adequate training in the
use of compressed air and a complete evaluation of
fitness for diving. People with a medical history of
lung cysts or spontaneous collapsed lung (pneumothorax), and those with active asthma or other
lung disease must not dive, for they would be at
extreme risk for gas embolism. Patients with conditions such as alcoholism and drug abuse are also discouraged from diving. Individuals with certain other
medical conditions such as diabetes may be able to
dive safely with careful training and supervision.
Resources
ORGANIZATIONS

American College of Hyperbaric Medicine. PO Box 25914130, Houston, Texas 77265. (713) 528-0657. <http://
www.hyperbaricmedicine.org>.
Divers Alert Network. The Peter B. Bennett Center, 6 West
Colony Place, Durham, NC 27705. (800) 446-2671.
<http://www.diversalertnetwork.org>.
Undersea and Hyperbaric Medical Society. 10531
Metropolitan Ave., Kensington, MD 20895. (301) 9422980. <http://www.uhms.org>.

Bethany Thivierge

Gas gangrene see Gangrene

Gastrectomy
Definition
Gastrectomy is the surgical removal of all or part
of the stomach.

Purpose
Gastrectomy is performed for several reasons,
most commonly to remove a malignant tumor or to
cure a perforated or bleeding stomach ulcer.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Gastrectomy for cancer
Removal of the tumor, often with removal of
surrounding lymph nodes, is the only curative treatment for various forms of gastric (stomach) cancer.
For many patients, this entails removing not just the
tumor but part of the stomach as well. The extent to
which lymph nodes should also be removed is a subject
of some debate, but some studies show additional
survival benefit associated with removal of a greater
number of lymph nodes.
Gastrectomy, either total or subtotal (also called
partial), is the treatment of choice for gastric adenocarcinomas, primary gastric lymphomas (originating
in the stomach), and the rare leiomyosarcomas (also
called gastric sarcomas). Adenocarcinomas are by far
the most common form of stomach cancer and are less
curable than the relatively uncommon lymphomas, for
which gastrectomy offers good odds for survival.
After gastrectomy, the surgeon may ‘‘reconstruct’’
the altered portions of the digestive tract so that it
continues to function. Several different surgical techniques are used, but, generally speaking, the surgeon
attaches any remaining portion of the stomach to the
small intestine.
Gastrectomy for gastric cancer is almost always
done by the traditional ‘‘open’’ surgery technique,
which requires a wide incision to open the abdomen.
However, some surgeons use a laparoscopic technique
that requires only a small incision. The laparoscope is
connected to a tiny video camera that projects a picture of the abdominal contents onto a monitor for
the surgeon’s viewing. The stomach is operated on
through this incision.
The potential benefits of laparoscopic surgery
include less postoperative pain, decreased hospitalization, and earlier return to normal activities. The use of
laparoscopic gastrectomy is limited, however. Only
patients with early stage gastric cancers or those
whose surgery is only intended for palliation—pain
and symptomatic relief rather than cure—should be
considered for this minimally invasive technique. It
can only be performed by surgeons experienced in
this type of surgery.
Gastrectomy for ulcers
Gastrectomy is also occasionally used in the treatment of severe peptic ulcer disease or its complications.
While the vast majority of peptic ulcers (gastric ulcers in
the stomach or duodenal ulcers in the duodenum)
are managed with medication, partial gastrectomy is
1555

Gastrectomy

breathing) should be administered. In the absence of
a pulse, cardiopulmonary resuscitation (CPR) must be
performed.

Gastrectomy

Total gastrectomy

Partial gastrectomy

Partial gastrectomy

Gastrectomy, the surgical removal of all or part of the stomach, is performed primarily to remove a malignant tumor or to cure a
bleeding stomach ulcer. Following the gastrectomy, the surgeon may reconstruct the altered portions of the digestive tract so
that it continues to function. (Illustration by Electronic Illustrators Group.)

sometimes required for peptic ulcer patients who have
complications. These include patients who do not
respond satisfactorily to medical therapy, those who
develop a bleeding or perforated ulcer, and those who
develop pyloric obstruction, a blockage to the exit
from the stomach.
The surgical procedure for severe ulcer disease is
also called an antrectomy, a limited form of gastrectomy in which the antrum, a portion of the stomach, is
removed. For duodenal ulcers, antrectomy may be
combined with other surgical procedures that are
aimed at reducing the secretion of gastric acid, which
is associated with ulcer formation. This additional
surgery is commonly a vagotomy, surgery on the
vagus nerve that disables the acid-producing portion
of the stomach.

Preparation
Before undergoing gastrectomy, patients may need
a variety of tests, such as x rays, computed tomography
scans (CT scans), ultrasonography, or endoscopic biopsies (microscopic examination of tissue), to assure the
diagnosis and localize the tumor or ulcer. Laparoscopy
may be done to diagnose a malignancy or to determine
the extent of a tumor that is already diagnosed. When a
tumor is strongly suspected, laparoscopy is often performed immediately before the surgery to remove the
tumor; this avoids the need to anesthetize the patient
twice and sometimes avoids the need for surgery altogether if the tumor found on laparoscopy is deemed
inoperable.
1556

Aftercare
It is important to follow any instructions that
have been given for postoperative care. Major surgery
usually requires a recuperation time of several weeks.

Risks
Surgery for peptic ulcer is effective, but it may
result in a variety of postoperative complications.
After gastrectomy, as many as 30% of patients have
significant symptoms. An operation called highly
selective vagotomy is now preferred for ulcer management, and is safer than gastrectomy.
After a gastrectomy, several abnormalities may
develop that produce symptoms related to food intake.
This happens largely because the stomach, which serves
as a food reservoir, has been reduced in its capacity by
the surgery. Other surgical procedures that often accompany gastrectomy for ulcer disease can also contribute
to later symptoms: vagotomy, which lessens acid production and slows stomach emptying, and pyloroplasty,
which enlarges the opening between the stomach and
small intestine to facilitate emptying of the stomach.
Some patients experience light-headedness, heart
palpitations or racing heart, sweating, and nausea and
vomiting after a meal. These may be symptoms of
‘‘dumping syndrome,’’ as food is rapidly ‘‘dumped’’
into the small intestine from the stomach. This is
treated by adjusting the diet and pattern of eating,
for example, eating smaller, more frequent meals,
and limiting liquids.
GALE ENCYCLOPEDIA OF MEDICINE

Antrectomy—A surgical procedure for ulcer disease in which the antrum, a portion of the stomach,
is removed.
Laparoscopy—The examination of the inside of the
abdomen through a lighted tube, sometimes
accompanied by surgery.

Patients who have abdominal bloating and pain
after eating, frequently followed by nausea and vomiting, may have what is called the afferent loop syndrome.
This is treated by surgical correction. Patients who have
early satiety (feeling of fullness after eating), abdominal
discomfort, and vomiting may have bile reflux gastritis
(also called bilious vomiting), which is also surgically
correctable. Many patients also experience weight loss.

Most studies have shown that patients can have an
acceptable quality of life after gastrectomy for a potentially curable gastric cancer. Many patients will maintain
a healthy appetite and eat a normal diet. Others may lose
weight and not enjoy meals as much. Some studies show
that patients who have total gastrectomies have more
disease-related or treatment-related symptoms after surgery and poorer physical function than patients who
have subtotal gastrectomies. There does not appear to
be much difference, however, in emotional status or
social activity level between patients who have undergone total versus subtotal gastrectomies.
Resources
BOOKS

Feldman, Mark., et al., editors. ‘‘Stomach and Duodenum:
Complications of Surgery for Peptic Ulcer Disease.’’ In
Steisenger & Fordtran’s Gastrointestinal and Liver
Disease. Philadelphia: W. B. Saunders Co., 1998.

Caroline A. Helwick

Reactive hypoglycemia is a condition that results
when blood sugar becomes too high after a meal,
stimulating the release of insulin, about two hours
after eating. A high-protein diet and smaller meals
are advised.
Ulcers recur in a small percentage of patients after
surgery for peptic ulcer, usually in the first few years.
Further surgery is usually necessary.
Vitamin and mineral supplementation is necessary after gastrectomy to correct certain deficiencies,
especially vitamin B12, iron, and folate. Vitamin D and
calcium are also needed to prevent and treat the bone
problems that often occur. These include softening
and bending of the bones, which can produce pain,
and osteoporosis, a loss of bone mass. According to
one study, the risk for spinal fractures may be as high
as 50% after gastrectomy.
Depending on the extent of surgery, the risk for
post-operative death after gastrectomy for gastric
cancer has been reported as 1–3% and the risk of
non-fatal complications as 9–18%.

Normal results
Overall survival after gastrectomy for gastric
cancer varies greatly by the stage of disease at the
time of surgery. For early gastric cancer, the five-year
survival rate is up to 80–90%; for late-stage disease,
the prognosis is bad. For gastric adenocarcinomas that
are amenable to gastrectomy, the five-year survival rate
is 10–30%, depending on the location of the tumor. The
prognosis for patients with gastric lymphoma is better,
with five-year survival rates reported at 40–60%.
GALE ENCYCLOPEDIA OF MEDICINE

Gastric acid determination
Definition
Gastric acid determination, also known as stomach acid determination, gastric analysis, or basal
gastric secretion, is a procedure to evaluate gastric
(stomach) function. The test specifically determines
the presence of gastric acid, as well as the amount of
gastric acid secreted. It is often done in conjunction
with the gastric acid stimulation test, a procedure that
measures gastric acid output after injection of a drug
to stimulate gastric acid secretion.

Purpose
The purpose of the gastric acid determination is to
evaluate gastric function by measuring the amount of
acid as suctioned directly from the stomach. The complete gastric acid determination includes the basal
gastric secretion test, which measures acid secretion
while the patient is in a fasting state (nothing to eat or
drink), followed by the gastric acid stimulation test,
which measures the secretion of gastric acid for one
hour after injection of pentagastrin or a similar drug
that stimulates gastric acid output. The Gastric acid
stimulation test is done when the basal secretion test
suggests abnormalities in gastric secretion. It is normally performed immediately afterward.
1557

Gastric acid determination

KEY TERMS

Gastric acid determination

The basal gastric secretion test is indicated for
patients with obscure gastric pain, loss of appetite,
and weight loss. It is also utilized for suspected peptic
(related to the stomach) ulcer, severe stomach inflammation (gastritis), and Zollinger-Ellison (Z-E) syndrome (a condition in which a pancreatic tumor,
called a gastrinoma, stimulates the stomach to secrete
excessive amounts of acid, resulting in peptic ulcers).
Because external factors like the sight or odor of food,
as well as psychological stress, can stimulate gastric
secretion, accurate testing requires that the patient be
relaxed and isolated from all sources of sensory stimulation. Abnormal basal secretion can suggest various
gastric and duodenal disorders, so further evaluation
requires the gastric acid stimulation test.
The gastric acid stimulation test is indicated when
abnormalities are found during the basal secretion
test. These abnormalities can be caused by a number
of disorders, including duodenal ulcer, pernicious anemia, and gastric cancer. The test will detect abnormalities, but x rays and other studies are necessary for a
definitive diagnosis.

Precautions
Because both the basal gastric secretion test and
the gastric acid stimulation test require insertion of a
gastric tube (intubation) through the mouth or nasal
passage, neither test is recommended for patients with
esophageal problems, aortic aneurysm, severe gastric
hemorrhage, or congestive heart failure. The gastric
acid stimulation test is also not recommended in
patients who are sensitive to pentagastrin (the drug
used to stimulate gastric acid output).

liquids during the test, and saliva must be ejected to
avoid diluting the stomach contents.
The four specimens collected during the test constitute the basal acid output. If analysis suggests abnormally low gastric secretion, the gastric acid stimulation
test is performed immediately afterward.
Gastric acid stimulation test
After the basal samples have been collected, the
tube remains in place for the gastric acid stimulation
test. Pentagastrin, or a similar drug that stimulates
gastric acid output, is injected under the skin (subcutaneously). After 15 minutes, a specimen is collected
every 15 minutes for one hour. These specimens are
called the poststimulation specimens. As is the case with
the basal gastric secretion test, the patient can have no
liquids during this test, and must eject saliva to avoid
diluting the stomach contents.

Preparation
The patient should be fasting (nothing to eat or
drink after the evening meal) on the day prior to the
test, but may have water up to one hour before the test.
Antacids, anticholinergics, cholinergics, alcohol, H2receptor antagonists (Tagamet, Pepcid, Axid, Zantac),
reserpine, adrenergic blockers, and adrenocorticosteroids should be withheld for one to three days before
the test, as the physician requests. If pentagastrin is to
be administered for the gastric acid secretion test,
medical supervision should be maintained, as possible
side effects may occur.

Aftercare
Description
This test, whether performed for basal gastric acid
secretion, gastric acid stimulation, or both, requires
the passage of a lubricated rubber tube, either by
mouth or through the nasal passage, while the patient
is in a sitting or reclining position on the left side. The
tube is situated in the stomach, with proper positioning confirmed by fluoroscopy or x ray.
Basal gastric acid secretion
After a wait of approximately 10–15 minutes for
the patient to adjust to the presence of the tube, and
with the patient in a sitting position, specimens are
obtained every 15 minutes for a period of 90 minutes.
The first two specimens are discarded to eliminate
gastric contents that might be affected by the stress
of the intubation process. The patient is allowed no
1558

Complications such as nausea, vomiting, and
abdominal distention or pain are possible following
removal of the gastric tube. If the patient has a sore
throat, soothing lozenges may be given. The patient
may also resume the usual diet and any medications
that were withheld for the test(s).

Risks
There is a slight risk that the gastric tube may be
inserted improperly, entering the windpipe (trachea)
and not the esophagus. If this happens, the patient
may have a difficult time breathing or may experience
a coughing spell until the tube is removed and reinserted properly. Also, because the tube can be difficult
to swallow, if a patient has an overactive gag reflex,
there may be a transient rise in blood pressure due to
anxiety.
GALE ENCYCLOPEDIA OF MEDICINE

Achlorhydria—An abnormal condition in which
hydrochloric acid is absent from the secretions of
the gastric glands in the stomach.
Pernicious anemia—One of the main types of anemia, caused by inadequate absorption of vitamin
B12. Symptoms include tingling in the hands, legs,
and feet, spastic movements, weight loss, confusion,
depression, and decreased intellectual function.
Zollinger-Ellison syndrome—A rare condition
characterized by severe and recurrent peptic ulcers
in the stomach, duodenum, and upper small intestine, caused by a tumor, or tumors, usually found in
the pancreas. The tumor secretes the hormone gastrin, which stimulates the stomach and duodenum
to produce large quantities of acid, leading to
ulceration. Most often cancerous, the tumor must
be removed surgically; otherwise total surgical
removal of the stomach is necessary.

BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Gastric carcinoma see Stomach cancer

Gastric emptying scan
Definition
A gastric emptying scan (GES) is an x-ray exam
using special radioactive material that allows physicians to identify abnormalities related to emptying of
the stomach. Diseases that involve changes in the way
the stomach contracts (motility disorders) are best
diagnosed by this test.

Purpose
Normal results
Reference values for the basal gastric secretion test
vary by laboratory, but are usually within the following ranges:


men: 1–5 mEq/h



women: 0.2–3.8 mEq/h

Reference values for the gastric acid stimulation
test vary by laboratory, but are usually within the
following ranges:


men: 18–28 mEq/h



women: 11–21 mEq/h

Abnormal results
Abnormal findings in the basal gastric secretion
test are considered nonspecific and must be evaluated
in conjunction with the results of a gastric acid stimulation test. Elevated secretion may suggest different
types of ulcers; when markedly elevated, ZollingerEllison syndrome is suspected. Depressed secretion
can indicate gastric cancer, while complete absence
of secretion (achlorhydria) may suggest pernicious
anemia.
Elevated gastric secretion levels in the gastric acid
stimulation test may be indicative of duodenal ulcer;
high levels of secretion again suggest Zollinger-Ellison
syndrome.
GALE ENCYCLOPEDIA OF MEDICINE

The study is used most frequently to evaluate
patients who have symptoms suggestive of decreased,
delayed, or rapid gastric emptying, and no visible
abnormality to explain their symptoms.
Symptoms pointing to a delay in gastric emptying
are non-specific, and may be due to a number of
causes, such as ulcers, diabetes, tumors, and others.
These symptoms include nausea, upper abdominal
bloating, and at times vomiting. Another significant
symptom is called ‘‘early satiety,’’ which means feeling
full after eating only a small amount of food. In some
patients, weight loss is also present. In addition to
symptoms, the finding of a large amount of material
in the stomach after an overnight fast suggests abnormal emptying, but does not distinguish between an
actual blockage or an irregularity in gastric contractions. It is therefore essential to find out what is causing material to remain in the stomach.
Since many diseases can produce the above symptoms, structural lesions (such as tumors or regions
of narrowing or scar tissue) need to be ruled out
first. This is usually done by upper gastrointestinal
series test or by endoscopy (examination of the
inside of an organ, in this instance the stomach,
with an instrument that has a light at the end of it
and an optical system for examination of the organ).
Once it is clear that a mechanical or physical lesion
is not the cause of symptoms, attempts to document
an abnormality in the nervous or muscular function
1559

Gastric emptying scan

Resources

KEY TERMS

Gastrinoma

KEY TERMS
Endoscopy—The examination of the inside of an
organ with an instrument that has a light at the end of
it and an optical system for examination of the organ.
Motility—Motility is spontaneous movement. One
example is the automatic stomach contractions that
move the food content along from the stomach into
the intestines. A motility disease is one that involves
changes in the way the stomach contracts.

of the stomach is then begun. GES is usually the first
step in that evaluation.

Precautions
The exam should not be performed on pregnant
women, but is otherwise quite safe. Since eggs are
usually used to hold the radioactive material, patients
should notify their physician if they are allergic to
eggs. However, other materials can be used in place
of an egg.

and solid meal used. The value is expressed as a percentage of emptying over a period of time. For a
technetium-filled egg sandwich, normal emptying is
78 minutes for half the material to leave the stomach,
with a variation of 11 minutes either way.

Abnormal results
GES scan studies that show emptying of the stomach in a longer than accepted period is abnormal.
Severity of test results and symptoms do not always
match; therefore, the physician must carefully interpret
these findings. Diabetic injury to the nerves that supply
the stomach (called diabetic gastroparesis) is one of the
most common causes of abnormal gastric motility.
However, up to 30% of patients have no obvious
cause to explain the abnormal results and symptoms.
These cases are called idiopathic (of unknown cause).
GES is often used to follow the effect of medications
used for treatment of motility disorders.
Resources
ORGANIZATIONS

American Pseudo-Obstruction and Hirschprung’s Disease
Society. 158 Pleasant St., North Andover, MA 018452797. <http://www.tiac.net/users/aphs>.

Description
Gastric emptying scans have undergone several
changes since the initial studies in the late 1970s.
During the study, patients are asked to ingest an egg
sandwich containing a radioactive substance (for example, technetium) that can be followed by a special camera. The emptying of the material from the stomach is
then followed and displayed both in the form of an
image, as well as the percentage emptied over several
hours (generally two and four hours). Studies are in
progress using substances that are not radioactive, but
this procedure is not available to the patient as of yet.

Preparation
The only preparation involved is for the patient to
fast overnight before the test.

Risks
The radiation exposure during the study is quite
small and safe, unless the patient is pregnant.

Normal results
There are several different measurements considered normal, depending on the radioactive material
1560

David Kaminstein, MD

Gastric lavage see Stomach flushing
Gastric stapling see Obesity surgery
Gastric ulcers see Ulcers (digestive)

Gastrinoma
Definition
Gastrinomas are tumors associated with a rare
gastroenterological disorder known as ZollingerEllison syndrome (ZES). They occur primarily in the
pancreas and duodenum (beginning of the small intestine) and secrete large quantities of the hormone gastrin, triggering gastric acid production that produces
ulcers. They may be malignant (cancerous) or benign.

Description
Gastrinomas are an integral part of the ZollingerEllison syndrome (ZES). In fact, ZES is also known as
gastrinoma. This syndrome consists of ulcer disease
in the upper gastrointestinal tract, marked increases
GALE ENCYCLOPEDIA OF MEDICINE

Gastrinomas may occur randomly and sporadically, or they may be inherited as part of a genetic
condition called multiple endocrine neoplasia type 1
(MEN-1) syndrome. About half of persons with
MEN-1 have gastrinomas, which tend to be more
numerous and smaller than tumors in sporadic cases.
About half of ZES patients have multiple gastrinomas, which can vary in size from 1–20 mm.
Gastrinomas found in the pancreas are usually much
larger than duodenal gastrinomas. About two thirds
of gastrinomas are malignant (cancerous). These
usually grow slowly, but some may invade surrounding sites rapidly and metastasize (spread) widely.
Sometimes, gastrinomas are found only in the lymph
nodes, and it is uncertain whether these malignancies
have originated in the lymph nodes or have metastasized from a tumor not visible in the pancreas or
duodenum.
There is some evidence that the more malignant
form of gastrinomas is more frequent in larger pancreatic tumors, especially in females and in persons
with a shorter disease symptom duration and higher
serum gastrin levels.

Causes and symptoms
Most persons with gastrinomas secrete profound
amounts of gastric acid, and almost all develop ulcers,
mostly in the duodenum or stomach. Early in the
course of the disease, symptoms are typical of peptic
ulcers, however once the disease is established, the
ulcers become more persistent and symptomatic, and
may respond poorly to standard anti-ulcer therapy.
Abdominal pain is the predominant symptom of ulcer
disease. About 40% of patients have diarrhea as well.
In some patients, diarrhea is the primary symptom of
gastrinoma.

Diagnosis
Persons with gastrinomas have many of the same
symptoms as persons with ulcers. Their levels of gastric acid, however, are usually far greater than those in
common ulcer disease. Gastrinomas are usually diagnosed by a blood test that measures the level of gastrin
in the blood. Patients with gastrinomas often have
gastrin levels more than 200 pg/mL, which is 4–10
GALE ENCYCLOPEDIA OF MEDICINE

times higher than normal. Serum gastrin levels as
high as 450,000 pg/mL have occurred.
When the serum gastrin test does not show these
extremely high levels of gastrin, patients may be given
certain foods or injections in an attempt to provoke a
response that will help diagnose the condition. The
most useful of these provocative tests is the secretin
injection test (or secretin stimulation or provocative
test), which will almost always produce a positive
response in persons with gastrinomas but seldom in
persons without them.
Surgically, gastrinomas are often difficult to
locate, even with careful inspection. They may be
missed in at least 10–20% of patients with ZES.
Gastrinomas are sometimes found only because they
have metastasized and produced symptoms related to
the spread of malignancy. Such metastasis may be the
most reliable indication of whether the gastrinoma is
malignant or benign.
Diagnostic imaging techniques help locate the
gastrinomas. The most sophisticated is an x-ray test
called radionuclide octreotide scanning (also known
as somatostatin receptor scintigraphy or 111In pentetreotide SPECT). A study by the National Institutes of
Health (NIH) found this test to be superior to other
imaging methods, such as computed tomography scan
(CT) or magnetic resonance imaging (MRI), in pinpointing the location of tumors and guiding physicians in treatment.
Approximately half of all gastrinomas do not
show up on imaging studies. Therefore, exploratory
surgery is often recommended to try to locate and
remove the tumors.

Treatment
Therapy for gastrinomas should be individualized, since patients tend to have varying degrees of
disease and symptoms. Treatment is aimed at eliminating the overproduction of gastric acid and removing the gastrin-producing tumors.
Drugs
Gastrinomas may not be easily treated by the
standard anti-ulcer approaches. The medical treatment of choice is with drugs called proton pump inhibitors, such as omeprazole or lansoprazole, daily.
These drugs are potent inhibitors of gastric acid.
High doses of H-2 receptor antagonists may also
reduce gastric acid secretion, improve symptoms, and
induce ulcer healing. These drugs must be continued
indefinitely, since even a brief discontinuation will
1561

Gastrinoma

in the secretion of gastric acid in the stomach, and
tumors of the islet cells in the pancreas. The tumors
produce large amounts of gastrin that are responsible
for the characteristics of Zollinger-Ellison syndrome,
namely severe ulcer disease. Although usually located
within the pancreas, they may occur in other organs.

Gastritis

cause ulcer recurrence. Antacids may provide some
relief, but it is usually not longlasting or healing.
Surgery
Because of the likelihood that gastrinomas may be
malignant, in both sporadic tumors and those associated with the inherited MEN-1 syndrome, surgery to
locate and remove gastrinomas is frequently advised.
It is now known that complete surgical removal of
gastrinomas can cure the overproduction of gastrin,
even in patients who have metastases to the lymph
nodes. Surgery in patients with MEN-1 and ZES,
however, remains controversial since the benefit is
less clear.
Freedom from disease after surgery is judged by
improved symptoms, reduced gastric acid production,
reduced need for drug therapy, normalization of
serum gastrin levels, and normalization of results
from the secretin stimulation test and imaging studies.

Prognosis
Medical therapy often controls symptoms, and
surgery may or may not cure gastrinoma. About
50% of ZES patients in whom gastrinomas are not
removed will die from malignant spread of the tumor.
In patients with gastrinomas as part of MEN-1 syndrome, the cure rate is extremely low.
A NIH study of patients who had surgical
removal of gastrinomas found that 42% were disease-free one year after surgery and 35% were disease-free at five years. Disease recurrences can often
be detected with a serum gastrin test or secretin stimulation test.
When gastrinomas are malignant, they often grow
slowly. The principal sites of metastasis are the regional lymph nodes and liver, but they may also spread to
other structures. About one quarter of patients with
gastrinomas have liver metastases at the time of diagnosis. This appears to be more frequent with pancreatic gastrinomas than duodenal gastrinomas.
Metastases of malignant gastrinomas to the liver
is very serious. Survival five years after diagnosis is
20–30%, however patients with gastrinomas found
only in the lymph nodes have been known to live as
long as 25 years after diagnosis, without evidence of
further tumor spread. In fact, the life expectancy of
patients with gastrinomas that have spread to the
lymph nodes is no different from that of patients
with gastrinomas that cannot even be found at surgery
for about 90%, five years after diagnosis.
1562

KEY TERMS
Gastrin—A hormone secreted in the stomach that is
involved in the production of gastric acid.
Overproduction of gastric acid contributes to peptic ulcer formation.
Multiple endocrine neoplasia type 1 (MEN-1)—An
inherited condition marked by multiple malignancies of the pituitary gland, parathyroid gland, and
islet cells of the pancreas. About half of MEN-1
patients with pancreatic islet cell tumors will have
gastrinomas, gastrin-producing tumors that lead to
ulcer disease.
Peptic ulcer—An eroded area in the stomach lining
or in the first part of the duodenum (beginning of the
small intestine).
Serum gastrin test—A laboratory test that is performed on a blood sample to determine that level
of the hormone gastrin. High levels of gastrin indicate the presence a duodenal ulcer or a gastrinoma.
Sporadic—Occurring at random or by chance, and
not as a result of a genetically determined, or inherited, trait.

Resources
ORGANIZATIONS

National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.

Caroline A. Helwick

Gastritis
Definition
Gastritis commonly refers to inflammation of the
lining of the stomach, but the term is often used to
cover a variety of symptoms resulting from stomach
lining inflammation and symptoms of burning or discomfort. True gastritis comes in several forms and is
diagnosed using a combination of tests. In the 1990s,
scientists discovered that the main cause of true gastritis is infection from a bacterium called Helicobacter
pylori (H. pylori).
GALE ENCYCLOPEDIA OF MEDICINE

Gastritis should not be confused with common
symptoms of upper abdominal discomfort. It has been
associated with resulting ulcers, particularly peptic
ulcers. And in some cases, chronic gastritis can lead to
more serious complications.

such as those in intensive care. Stress erosions may
develop suddenly as a result of severe trauma or
stress to the stomach lining.


Atrophic gastritis is the result of chronic gastritis
which is leading to atrophy, or decrease in size and
wasting away, of the gastric lining. Gastric atrophy is
the final stage of chronic gastritis and may be a
precursor to gastric cancer.



Superficial gastritis is a term often used to describe
the initial stages of chronic gastritis.



Uncommon specific forms of gastritis include granulomatous, eosiniphilic and lymphocytic gastritis.

Nonerosive H. pylori gastritis
The main cause of true gastritis is H. pylori infection. H. pylori is indicated in an average of 90% of
patients with chronic gastritis. This form of nonerosive
gastritis is the result of infection with Helicobacter
pylori bacterium, a microorganism whose outer layer
is resistant to the normal effects of stomach acid in
breaking down bacteria.
The resistance of H. pylori means that the bacterium may rest in the stomach for long periods of times,
even years, and eventually cause symptoms of gastritis or ulcers when other factors are introduced, such
as the presence of specific genes or ingestion of nonsteroidal anti-inflammatory drugs (NSAIDS). Study
of the role of H. pylori in development of gastritis and
peptic ulcers has disproved the former belief that
stress lead to most stomach and duodenal ulcers
and has resulted in improved treatment and reduction of stomach ulcers. H. pylori is most likely transmitted between humans, although the specific routes
of transmission were still under study in early 1998.
Studies were also underway to determine the role of
H. pylori and resulting chronic gastritis in development of gastric cancer.
Erosive and hemorrhagic gastritis
After H. pylori, the second most common
cause of chronic gastritis is use of nonsteroidal antiinflammatory drugs. These commonly used pain killers,
including aspirin, fenoprofen, ibuprofen and naproxen,
among others, can lead to gastritis and peptic ulcers.
Other forms of erosive gastritis are those due to alcohol
and corrosive agents or due to trauma such as ingestion
of foreign bodies.
Other forms of gastritis
Clinicians differ on the classification of the less
common and specific forms of gastritis, particularly
since there is so much overlap with H. pylori in development of chronic gastritis and complications of
gastritis. Other types of gastritis that may be diagnosed include:


Acute stress gastritis–the most serious form of gastritis which usually occurs in critically ill patients,

GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Nonerosive H. pylori gastritis
H. pylori gastritis is caused by infection from the
H. pylori bacterium. It is believed that most infection
occurs in childhood. The route of its transmission was
still under study in 1998 and clinicians guessed that
there may be more than one route for the bacterium.
Its prevalence and distribution differs in nations
around the world. The presence of H. pylori has been
detected in 86–99% of patients with chronic superficial gastritis. However, physicians are still learning
about the link of H. pylori to chronic gastritis and
peptic ulcers, since many patients with H. pylori infection do not develop symptoms or peptic ulcers.
H. pylori is also seen in 90–100% of patients with
duodenal ulcers.
Symptoms of H. pylori gastritis include abdominal pain and reduced acid secretion in the stomach.
However, the majority of patients with H. pylori infection suffer no symptoms, even though the infection
may lead to ulcers and resulting symptoms. Ulcer
symptoms include dull, gnawing pain, often two to
three hours after meals and pain in the middle of the
night when the stomach is empty.
Erosive and hemorrhagic gastritis
The most common cause of this form of gastritis is
use of NSAIDS. Other causes may be alcoholism or
stress from surgery or critical illness. The role of
NSAIDS in development of gastritis and peptic ulcers
depends on the dose level. Although even low doses of
aspirin or other nonsteroidal anti-inflammatory drugs
may cause some gastric upset, low doses generally will
not lead to gastritis. However, as many as 10–30% of
patients on higher and more frequent doses of
NSAIDS, such as those with chronic arthritis, may
develop gastric ulcers. In 1998, studies were underway
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Gastritis

Description

Gastritis

to understand the role of H. pylori in gastritis and
ulcers among patients using NSAIDS.
Patients with erosive gastritis may also show no
symptoms. When symptoms do occur, they may
include anorexia nervosa, gastric pain, nausea and
vomiting.
Other Forms of Gastritis
Less common forms of gastritis may result from a
number of generalized diseases or from complications
of chronic gastritis. Any number of mechanisms may
cause various less common forms of gastritis and they
may differ slightly in their symptoms and clinical
signs. However, they all have in common inflammation of the gastric mucosa.

Diagnosis
Nonerosive H. pylori gastritis
H. pylori gastritis is easily diagnosed through the
use of the urea breath test. This test detects active
presence of H. pylori infection. Other serological
tests, which may be readily available in a physician’s
office, may be used to detect H. pylori infection. Newly
developed versions offer rapid diagnosis. The choice
of test will depend on cost, availability and the physician’s experience, since nearly all of the available tests
have an accuracy rate of 90% or better. Endoscopy, or
the examination of the stomach area using a hollow
tube inserted through the mouth, may be ordered to
confirm diagnosis. A biopsy of the gastric lining may
also be ordered.
Erosive or hemorrhagic gastritis
Clinical history of the patient may be particularly
important in the diagnosis of this type of gastritis,
since its cause is most often the result of chronic use
of NSAIDS, alcoholism, or other substances.
Other forms of gastritis
Gastritis that has developed to the stage of duodenal or gastric ulcers usually requires endoscopy for
diagnosis. It allows the physician to perform a biopsy
for possible malignancy and for H. pylori. Sometimes,
an upper gastrointestinal x-ray study with barium is
ordered. Some diseases such as Zollinger-Ellison syndrome, an ulcer disease of the upper gastrointestinal
tract, may show large mucosal folds in the stomach
and duodenum on radiographs or in endoscopy. Other
tests check for changes in gastric function.
1564

Treatment
H. pylori gastritis
The discovery of H. pylori’s role in development
of gastritis and ulcers has led to improved treatment of
chronic gastritis. In particular, relapse rates for duodenal and gastric ulcers has been reduced with successful treatment of H. pylori infection. Since the infection
can be treated with antibiotics, the bacterium can be
completely eliminated up to 90% of the time.
Although H. pylori can be successfully treated, the
treatment may be uncomfortable for patients and
relies heavily on patient compliance. In 1998, studies
were underway to identify the best treatment method
based on simplicity, patient cooperation and results.
No single antibiotic had been found which would
eliminate H. pylori on its own, so a combination of
antibiotics has been prescribed to treat the infection.
DUAL THERAPY. Dual therapy involves the use of
an antibiotic and a proton pump inhibitor. Proton
pump inhibitors help reduce stomach acid by halting
the mechanism that pumps acid into the stomach. This
also helps promote healing of ulcers or inflammation.
Dual therapy has not been proven to be as effective as
triple therapy, but may be ordered for some patients
who can more comfortably handle the use of less drugs
and will therefore more likely follow the two-week
course of therapy.
TRIPLE THERAPY. As of early 1998, triple therapy
was the preferred treatment for patients with H. pylori
gastritis. It is estimated that triple therapy successfully
eliminates 80–95% of H. pylori cases. This treatment
regimen usually involves a two-week course of three
drugs. An antibiotic such as amoxicillin or tetracycline, and another antibiotic such as clarithomycin or
metronidazole are used in combination with bismuth
subsalicylate, a substance found in the over-the-counter medication, Pepto-Bismol, which helps protect the
lining of the stomach from acid. Physicians were
experimenting with various combinations of drugs
and time of treatment to balance side effects with
effectiveness. Side effects of triple therapy are not
serious, but may cause enough discomfort that
patients are not inclined to follow the treatment.
OTHER TREATMENT THERAPIES. Scientists have
experimented with quadruple therapy, which adds an
antisecretory drug, or one which suppresses gastric
secretion, to the standard triple therapy. One study
showed this therapy to be effective with only a week’s
course of treatment in more than 90% of patients.
Short course therapy was attempted with triple therapy involving antibiotics and a proton pump inhibitor

GALE ENCYCLOPEDIA OF MEDICINE

MEASURING H. PYLORI TREATMENT EFFECTIVENESS. In
order to ensure that H. pylori has been eradicated,
physicians will test patients following treatment. The
breath test is the preferred method to check for
remaining signs of H. pylori.

Treatment of erosive gastritis
Since few patients with this form of gastritis show
symptoms, treatment may depend on severity of
symptoms. When symptoms do occur, patients may
be treated with therapy similar to that for H. pylori,
especially since some studies have demonstrated a link
between H. pylori and NSAIDS in causing ulcers.
Avoidance of NSAIDS will most likely be prescribed.
Other forms of gastritis
Specific treatment will depend on the cause and
type of gastritis. These may include prednisone or antibiotics. Critically ill patients at high risk for bleeding
may be treated with preventive drugs to reduce risk of
acute stress gastritis. If stress gastritis does occur, the
patient is treated with constant infusion of a drug to
stop bleeding. Sometimes surgery is recommended, but
is weighed with the possibility of surgical complications
or death. Once torrential bleeding occurs in acute stress
gastritis, mortality is as high as greater than 60%.

Alternative treatment
Alternative forms of treatment for gastritis and
ulcers should be used cautiously and in conjunction
with conventional medical care, particularly now that
scientists have confirmed the role of H. pylori in gastritis and ulcers. Alternative treatments can help
address gastritis symptoms with diet and nutritional
supplements, herbal medicine and ayurvedic medicine.
It is believed that zinc, vitamin A and beta-carotene
aid in the stomach lining’s ability to repair and regenerate itself. Herbs thought to stimulate the immune
system and reduce inflammation include echinacea
(Echinacea spp.) and goldenseal (Hydrastis canadensis). Ayurvedic medicine involves meditation. There
are also certain herbs and nutritional supplements
aimed at helping to treat ulcers.

Prognosis
The discovery of H. pylori has improved the prognosis for patients with gastritis and ulcers. Since
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Duodenal—Refers to the duodenum, or the first
part of the small intestine.
Gastric—Relating to the stomach.
Mucosa—The mucous membrane, or the thin layer
which lines body cavities and passages.
Ulcer—A break in the skin or mucous membrane. It
can fester and pus like a sore.

treatment exists to eradicate the infection, recurrence
is much less common. As of 1998, the only patients
requiring treatment for H. pylori were those at high
risk because of factors such as NSAIDS use or for
those with ulcers and other complicating factors or
symptoms. Research will continue into the most effective treatment of H. pylori, especially in light of the
bacterium’s resistance to certain antibiotics. Regular
treatment of patients with gastric and duodenal ulcers
has been recommended, since H. pylori plays such a
consistently high role in development of ulcers. It is
believed that H. pylori also plays a role in the eventual
development of serious gastritis complications and
cancer. Detection and treatment of H. pylori infection
may help reduce occurrence of these diseases. The
prognosis for patients with acute stress gastritis is
much poorer, with a 60 percent or higher mortality
rate among those bleeding heavily.

Prevention
The widespread detection and treatment of
H. pylori as a preventive measure in gastritis has been
discussed but not resolved. Until more is known about
the routes through which H. pylori is spread, specific
prevention recommendations are not available. Erosive
gastritis from NSAIDS can be prevented with cessation
of use of these drugs. An education campaign was
launched in 1998 to educate patients, particularly an
aging population of arthritis sufferers, about risk for
ulcers from NSAIDS and alternative drugs.
Resources
PERIODICALS

Podolski, J. L. ‘‘Recent Advances in Peptic Ulcer Disease:
H. pylori Infection and Its Treatement.’’
Gastroenterology Nursing 19, no. 4: 128-136.
ORGANIZATIONS

National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570.
1565

Gastritis

and seemed effective in eliminating H. pylori in one
week for more than 90% of patients. The goal is to
develop the most effective therapy combination that
can work in one week of treatment or less.

Gastroenteritis

(800) 891-5389. <http://www.niddk.nih.gov/health/
digest/nddic.htm>.
OTHER

American College of Gastroenterology Page. <http://
www.acg.org>.
HealthAnswers.com. <http://www.healthanswers.com>.

Teresa Odle

Gastroduodenostomy (Billroth I) see Ulcer
surgery

Gastroenteritis
Definition
Gastroenteritis is a catchall term for infection or
irritation of the digestive tract, particularly the stomach and intestine. It is frequently referred to as the
stomach or intestinal flu, although the influenza virus
is not associated with this illness. Major symptoms
include nausea and vomiting, diarrhea, and abdominal
cramps. These symptoms are sometimes also accompanied by fever and overall weakness. Gastroenteritis
typically lasts about three days. Adults usually recover
without problem, but children, the elderly, and anyone
with an underlying disease are more vulnerable to
complications such as dehydration.

Description
Gastroenteritis is an uncomfortable and inconvenient ailment, but it is rarely life-threatening in the
United States and other developed nations. However,
an estimated 220,000 children younger than age five are
hospitalized with gastroenteritis symptoms in the
United States annually. Of these children, 300 die as a
result of severe diarrhea and dehydration. In developing nations, diarrheal illnesses are a major source of
mortality. In 1990, approximately three million deaths
occurred worldwide as a result of diarrheal illness.
The most common cause of gastroenteritis is viral
infection. Viruses such as rotavirus, adenovirus, astrovirus, and calicivirus and small round-structured
viruses (SRSVs) are found all over the world.
Exposure typically occurs through the fecal-oral
route, such as by consuming foods contaminated by
fecal material related to poor sanitation. However, the
infective dose can be very low (approximately 100
virus particles), so other routes of transmission are
quite probable.
1566

Typically, children are more vulnerable to rotaviruses, the most significant cause of acute watery diarrhea. Annually, worldwide, rotaviruses are estimated to
cause 800,000 deaths in children below age five. For this
reason, much research has gone into developing a vaccine to protect children from this virus. Adults can be
infected with rotaviruses, but these infections typically
have minimal or no symptoms.
Children are also susceptible to adenoviruses
and astroviruses, which are minor causes of childhood gastroenteritis. Adults experience illness from
astroviruses as well, but the major causes of adult
viral gastroenteritis are the caliciviruses and SRSVs.
These viruses also cause illness in children. The SRSVs
are a type of calicivirus and include the Norwalk,
Southhampton, and Lonsdale viruses. These viruses
are the most likely to produce vomiting as a major
symptom.
Bacterial gastroenteritis is frequently a result of
poor sanitation, the lack of safe drinking water, or
contaminated food–conditions common in developing
nations. Natural or man-made disasters can make
underlying problems in sanitation and food safety
worse. In developed nations, the modern food production system potentially exposes millions of people to
disease-causing bacteria through its intensive production and distribution methods. Common types of bacterial gastroenteritis can be linked to Salmonella and
Campylobacter bacteria; however, Escherichia coli
0157 and Listeria monocytogenes
are creating
increased concern in developed nations. Cholera and
Shigella remain two diseases of great concern in developing countries, and research to develop long-term
vaccines against them is underway.

Causes and symptoms
Gastroenteritis arises from ingestion of viruses,
certain bacteria, or parasites. Food that has spoiled
may also cause illness. Certain medications and excessive alcohol can irritate the digestive tract to the point of
inducing gastroenteritis. Regardless of the cause, the
symptoms of gastroenteritis include diarrhea, nausea
and vomiting, and abdominal pain and cramps.
Sufferers may also experience bloating, low fever, and
overall tiredness. Typically, the symptoms last only two
to three days, but some viruses may last up to a week.
A usual bout of gastroenteritis shouldn’t require a
visit to the doctor. However, medical treatment is
essential if symptoms worsen or if there are complications. Infants, young children, the elderly, and persons
with underlying disease require special attention in
this regard.
GALE ENCYCLOPEDIA OF MEDICINE

recommend a diet that includes complex carbohydrates (e.g., rice, wheat, potatoes, bread, and cereal),
lean meats, yogurt, fruit, and vegetables. Milk and
other dairy products shouldn’t create problems if they
are part of the normal diet. Fatty foods or foods with a
lot of sugar should be avoided. These recommendations
are based on clinical experience and controlled trials,
but are not universally accepted.

If symptoms do not resolve within a week, an
infection or disorder more serious than gastroenteritis
may be involved. Symptoms of great concern include a
high fever (102 8 F [38.9 8C] or above), blood or mucus
in the diarrhea, blood in the vomit, and severe abdominal pain or swelling. These symptoms require prompt
medical attention.

Minimal to moderate dehydration is treated with
oral rehydrating solutions that contain glucose and
electrolytes. These solutions are commercially available under names such as Naturalyte, Pedialyte,
Infalyte, and Rehydralyte. Oral rehydrating solutions
are formulated based on physiological properties.
Fluids that are not based on these properties–such as
cola, apple juice, broth, and sports beverages–are not
recommended to treat dehydration. If vomiting interferes with oral rehydration, small frequent fluid intake
may be better tolerated. Should oral rehydration fail
or severe dehydration occur, medical treatment in the
form of intravenous (IV) therapy is required. IV therapy can be followed with oral rehydration as the
patient’s condition improves. Once normal hydration
is achieved, the patient can return to a regular diet.

Diagnosis
The symptoms of gastroenteritis are usually enough
to identify the illness. Unless there is an outbreak affecting several people or complications are encountered in
a particular case, identifying the specific cause of the
illness is not a priority. However, if identification of
the infectious agent is required, a stool sample will be
collected and analyzed for the presence of viruses, disease-causing (pathogenic) bacteria, or parasites.

Treatment
Gastroenteritis is a self-limiting illness which will
resolve by itself. However, for comfort and convenience, a person may use over-the-counter medications
such as Pepto Bismol to relieve the symptoms. These
medications work by altering the ability of the intestine to move or secrete spontaneously, absorbing toxins and water, or altering intestinal microflora. Some
over-the-counter medicines use more than one element
to treat symptoms.
If over-the-counter medications are ineffective
and medical treatment is sought, a doctor may prescribe a more powerful anti-diarrheal drug, such as
motofen or lomotil. Should pathogenic bacteria or
parasites be identified in the patient’s stool sample,
medications such as antibiotics will be prescribed.
It is important to stay hydrated and nourished
during a bout of gastroenteritis. If dehydration is
absent, the drinking of generous amounts of nonalcoholic fluids, such as water or juice, is adequate.
Caffeine, since it increases urine output, should be
avoided. The traditional BRAT diet–bananas,
rice, applesauce, and toast–is tolerated by the tender
gastrointestinal system, but it is not particularly
nutritious. Many, but not all, medical researchers
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
Symptoms of uncomplicated gastroenteritis can
be relieved with adjustments in diet, herbal remedies,
and homeopathy. An infusion of meadowsweet
(Filipendula ulmaria) may be effective in reducing nausea and stomach acidity. Once the worst symptoms are
relieved, slippery elm (Ulmus fulva) can help calm the
digestive tract. Of the homeopathic remedies available, Arsenicum album, ipecac, or Nux vomica are
three said to relieve the symptoms of gastroenteritis.
Probiotics, bacteria that are beneficial to a person’s health, are recommended during the recovery
phase of gastroenteritis. Specifically, live cultures of
Lactobacillus acidophilus are said to be effective in
soothing the digestive tract and returning the intestinal flora to normal. L. acidophilus is found in liveculture yogurt, as well as in capsule or powder form at
health food stores. The use of probiotics is found in
folk remedies and has some support in the medical
literature. Castor oil packs to the abdomen can reduce
inflammation and also reduce spasms or discomfort.

Prognosis
Gastroenteritis is usually resolved within two to
three days and there are no long-term effects. If dehydration occurs, recovery is extended by a few days.
1567

Gastroenteritis

The greatest danger presented by gastroenteritis is
dehydration. The loss of fluids through diarrhea and
vomiting can upset the body’s electrolyte balance, leading to potentially life-threatening problems such as heart
beat abnormalities (arrhythmia). The risk of dehydration increases as symptoms are prolonged. Dehydration
should be suspected if a dry mouth, increased or excessive
thirst, or scanty urination is experienced.

Gastrostomy

KEY TERMS

Gastrostomy

Dehydration—A condition in which the body lacks
the normal level of fluids, potentially impairing
normal body functions.
Electrolyte—An ion, or weakly charged element, that
conducts reactions and signals in the body. Examples
of electrolytes are sodium and potassium ions.
Glucose—A sugar that serves as the body’s primary
source of fuel.
Influenza—A virus that affects the respiratory system, causing fever, congestion, muscle aches, and
headaches.
Intravenous (IV) therapy—Administration of intravenous fluids.
Microflora—The bacterial population in the intestine.
Pathogenic bacteria—Bacteria that produce illness.
Probiotics—Bacteria that are beneficial to a person’s health, either through protecting the body
against pathogenic bacteria or assisting in recovery
from an illness.

Prevention
There are few steps that can be taken to avoid
gastroenteritis. Ensuring that food is well-cooked
and unspoiled can prevent bacterial gastroenteritis,
but may not be effective against viral gastroenteritis.
Resources
PERIODICALS

Hart, C. Anthony, and Nigel A. Cunliffe. ‘‘Viral
Gastroenteritis.’’ Current Opinion in Infectious Diseases
10 (1997): 408.
Moss, Peter J., and Michael W. McKendrick. ‘‘Bacterial
Gastroenteritis.’’ Current Opinion in Infectious Diseases
10 (1997): 402.

Julia Barrett

Gastroesophageal reflux see Heartburn
Gastrointestinal bleeding studies see GI
bleeding studies
Gastrointestinal study see Liver nuclear
medicine scan
Gastrojejunostomy see Ulcer surgery
Gastroschisis see Abdominal wall defects
1568

Definition
Gastrostomy is a surgical procedure for inserting
a tube through the abdomen wall and into the stomach. The tube is used for feeding or drainage.

Purpose
Gastrostomy is performed because a patient temporarily or permanently needs to be fed directly
through a tube in the stomach. Reasons for feeding
by gastrostomy include birth defects of the mouth,
esophagus, or stomach, and problems sucking or
swallowing.
Gastrostomy is also performed to provide drainage for the stomach when it is necessary to bypass a
long-standing obstruction of the stomach outlet into
the small intestine. Obstructions may be caused by
peptic ulcer scarring or a tumor.

Precautions
Gastrostomy is a relatively simple procedure. As
with any surgery, patients are more likely to experience complications if they are smokers, obese, use
alcohol heavily, or use illicit drugs. In addition, some
prescription medications may increase risks associated
with anesthesia.

Description
Gastrostomy, also called gastrostomy tube insertion, is surgery performed by a general surgeon to give
an external opening into the stomach. Surgery is performed either when the patient is under general
anesthesia–where the patient feels as if he is in a deep
sleep and has no awareness of what is happening–or
under local anesthesia. With local anesthesia, the
patient is awake, but the part of the body cut during
the operation is numbed.
A small incision is made on the left side of the
abdomen; then, an incision is made through the stomach. A small, flexible, hollow tube, usually made of
polyvinylchloride or rubber, is inserted into the stomach. The stomach is stitched closed around the tube,
and the incision is closed. The procedure is performed
at a hospital or free-standing surgery center.
The length of time the patient needs to remain in
the hospital depends on the age of the patient and the
patient’s general health. In some cases, the hospital
stay can be as short as one day, but often is longer.
GALE ENCYCLOPEDIA OF MEDICINE

Gaucher disease

Feeding
tube

Incision
site

Removable
cap

Balloon
Stomach

Gastrostomy is a procedure in which the surgeon makes an opening into the stomach and inserts a feeding tube for feeding or
for drainage. (Illustration by Electronic Illustrators Group.)

Normally, the stomach and abdomen heal in five to
seven days.
The cost of the surgery varies, depending on the
age and health of the patient. Younger, sicker patients
require more intensive, thus more expensive, care.

Preparation
Prior to the operation, the doctor will perform
endoscopy and take x rays of the gastrointestinal
tract. Blood and urine tests will also be performed,
and the patient may meet with the anesthesiologist to
evaluate any special conditions that might affect the
administration of anesthesia.

Aftercare
Immediately after the operation, the patient is fed
intravenously for at least 24 hours. Once bowel sounds
are heard, indicating that the gastrointestinal system is
working, the patient can begin clear liquid feedings
through the tube. Gradually feedings are increased.
Patient education concerning use and care of the
gastrostomy tube is very important. Patients and their
families are taught how to recognize and prevent infection around the tube, how to feed through the tube,
how to handle tube blockage, what to do if the tube
pulls out, and what normal activities can be continued.

KEY TERMS
Endoscopy—A procedure in which an instrument
containing a camera is inserted into the gastrointestinal tract so that the doctor can visually inspect
the gastrointestinal system.

Normal results
The patient is able to eat through the gastrostomy
tube, or the stomach can be drained through the tube.
Resources
OTHER

‘‘Stomach Tube Insertion.’’ HealthAnswers.com. <http://
www.healthanswers.com>.

Tish Davidson, A.M.

Gaucher disease
Definition

Risks
There are few risks associated with this surgery. The
main complications are infection, bleeding, dislodgment
of the tube, stomach bloating, nausea, and diarrhea.
GALE ENCYCLOPEDIA OF MEDICINE

Gaucher disease is a rare genetic disorder that
results in accumulation of fatty molecules called cerebrosides. It can have serious effects on numerous body
organs including the liver, spleen, bones and central
1569

Gaucher disease

nervous system. Treatments based on molecular biology are becoming available, but are very expensive.

Description
Gaucher disease was first described by the French
physician Philippe Gaucher in 1882. It is the most
common of a class of diseases called lysosomal storage
diseases, each of which is characterized by the accumulation of a specific chemical substance (a different
substance depending on the exact disease). Gaucher
disease is characterized by a wide array of different
symptoms and the severity of the disease ranges from
undetectable to lethal.
Three forms of the disease are recognized: Types
I, II and III. Type I is by far the most common and
shows the mildest symptoms. It is non-neuronopathic, meaning that the nervous system is not
attacked. The onset of Type I can occur at any age
in childhood or adult life with the average age of
onset at about 21 years. Some affected individuals
are have no symptoms throughout adult life. Type II,
the infantile form, accounts for less than 1% of
patients with Gaucher disease. It is neuronopathic
(attacks the nervous system); nervous system effects
are severe, and victims often die within the first year
of life. Type III most often has its onset during childhood and has some of the features of both the adult
and infantile forms. This affects less than 5% of
persons with Gaucher disease.
Gaucher disease is caused by the absence, or near
absence, of activity of an enzyme called glucocerebrosidase (GC). The normal action of GC is to break
down a common molecule called glucocerebroside. If
not broken down, glucocerebroside accumulates in
certain cells to levels that can cause damage, especially in the spleen, liver, and bone. The common link
among these organs is that they house a cell type
called a macrophage. A macrophage is a large cell
that surrounds and consumes a foreign substance
(such as bacteria) in the body. The cellular structures
in which glucocerebroside accumulates are called
lysosomes.
The three forms of Gaucher disease also differ in
their population genetics. Type I is most common in
persons of eastern European (Ashkenazi) Jewish descent. Among this population, the disease occurs at a
rate of one in 450 live births and about one in 10 to 15
persons are carriers, making it the most common
genetic disease affecting Jewish people. The other
two types are equally frequent in all ethnic groups.
Type II occurs at a rate of one in 100,000 live births,
1570

while Type III is estimated to occur in one in 50,000
live births.

Causes and symptoms
Lack of the GC enzyme is caused by a mutation
in the glucocerebrosidase gene. The gene is located on
chromosome 1. As of 2000, there have been over 100
mutations described in this gene that causes Gaucher
disease. Gaucher disease is inherited in an autosomal
recessive pattern. This means that two defective gene
copies must be inherited, one from each parent, for
the disease to manifest itself. Persons with only one
gene mutation are carriers for the disorder. A person
who is a carrier for Gaucher disease does not have
any symptoms and does not know he or she is a
carrier unless he or she has had specific testing.
When both parents are carriers for Gaucher disease,
there is a one in four chance (25%) in each pregnancy
for a child to have Gaucher disease. There is a two in
three chance that a healthy sibling of an affected child
is a carrier.
The results of Gaucher disease are widespread in
the body and include excessive growth of the liver and
spleen (hepatosplenomegaly), weakening of bones,
and, in acute cases, severe nervous system damage.
Many patients experience ‘‘bone crises,’’ which are
episodes of extreme pain in their bones.
There is a wide array of other problems that occur
with Gaucher disease, such as anemia (fewer than
normal red blood cells). Just how these other symptoms are caused is not known. Nor is it known why
some patients have very mild disease and others have
much more significant problems. Even identical twins
with the disease can have differing symptoms.

Diagnosis
Diagnosis of Gaucher disease, based initially on
the symptoms described above, can be confirmed by
microscopic, enzymatic, and molecular tests. Biopsy
(surgical removal of tissue from a problem area) of
tissue is helpful for microscopic diagnosis. When
biopsy tissue is examined under the microscope, cells
will appear swollen and will show characteristic features of the cytoplasm (part of the cell body along with
the nucleus) and nucleus. Enzyme tests will show deficiency (<30% of normal levels) of the enzyme GC.
Molecular analysis of DNA samples looking at four of
the more common mutations will show defects in the
gene for GC in 95% of Ashkenazi Jewish individuals
and in 75% of non-Jewish people. Diagnosis can be
performed prenatally (before birth) if the parents’
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis as to which of the three types of Gaucher
disease an individual has is based on the symptoms,
rather than on test results.

Treatment
Until the 1990s, only supportive therapy could
be offered. Analgesics are used to control pain.
Orthopedic treatment is used for bone fractures. In
some cases, surgical removal of the spleen may be
necessary. Several treatments for anemia have been
used, including vitamin and iron supplements, blood
transfusions, and bone marrow transplants.
The newest form of treatment for Gaucher disease is enzyme replacement therapy, in which GC
can be administered intravenously. The enzyme can
be prepared either by purification from placentas
(alglucerase) or by recombinant DNA manufacturing techniques (imiglucerase). Either way, the cost of
treatment ranges from $100,000 to $400,000 per year,
which can prevent many from obtaining treatment.
Enzyme replacement is effective at reducing most
Gaucher symptoms. The notable exception is neurologic damage in Type II disease, which remains unimproved by this treatment. This treatment is not
recommended for individuals who are asymptomatic.
As of 2000, the efficacy for the treatment of Type III
Gaucher disease is not known. Many questions remain
about enzyme replacement therapy in regard to
dosage, and method and frequency of administration.
The treatment program should be individualized for
each patient.

Prognosis
A patient’s expected lifespan varies greatly with
the type of Gaucher disease. Infants with Type II
disease have a life span of one to four years. Patients
with Types I and III of the disease have highly variable
outcomes with some patients dying in childhood and
others living full lives. Little is known about the reasons for this variability.

Prevention
Genetic counseling is advised for individuals with
Gaucher disease and for their relatives to accurately
assess risk and discuss testing options. For couples
who previously had a child with Gaucher or in situations where both parents are carriers for known
Gaucher mutations, prenatal diagnosis is available to
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cerebrosides—Fatty carbohydrates that occur in
the brain and nervous system.
Enzymatic replacement therapy—A treatment
method used to replace missing enzymes. It is possible to synthesize enzymes and then inject them
intravenously into patients.
Glucocerebroside—A cerebroside that contains
glucose in the molecule.

determine whether a pregnancy is affected. Families in
which a person has been diagnosed with Gaucher disease can have DNA testing, which enables other relatives to determine their carrier status. Prospective
parents can then use that information to conduct
family planning or to prepare for a child who may
have special circumstances.
Families in which both parents are known to be a
carrier of a mutation for Gaucher disease could consider preimplantation genetic diagnosis. This relatively new procedure can select an embryo without
both Gaucher disease mutations prior to implantation
of the embryo into the uterus. This technique is only
available at selected genetics centers.
As of the early 2000s, population screening for
Gaucher disease is not standard of care.
Resources
PERIODICALS

Beutler, E. ‘‘Gaucher Disease.’’ Archives of Internal
Medicine 159 (1999): 881-2.
ORGANIZATIONS

Alliance of Genetic Support Groups. 4301 Connecticut Ave.
NW, Suite 404, Washington, DC 20008. (202) 966-5557.
Fax: (202) 966-8553. <http://
www.geneticalliance.org>.
Children’s Gaucher Research Fund. PO Box 2123, Granite
Bay, CA 95746-2123. (916) 797-3700. Fax: (916) 7973707. <http://www.childrensgaucher.org>.
National Gaucher Foundation. 11140 Rockville Pike, Suite
350, Rockville, MD 20852-3106. (800) 925-8885.
<http://www.gaucherdisease.org>.
National Organization for Rare Disorders (NORD). PO
Box 8923, New Fairfield, CT 06812-8923. (203) 7466518 or (800) 999-6673. Fax: (203) 746-6481. <http://
www.rarediseases.org>.
OTHER

‘‘Cerezyme.’’ Genzyme Therapeutics. <http://
www.cerezyme.com>.
1571

Gaucher disease

mutations are known using amniocentesis or chorionic
villus sampling.

Gay and lesbian health

‘‘Gaucher Disease: Current Issues in Diagnosis and
Treatment.’’ <http://text.nlm.nih.gov/nih/ta/www/
16.html>.
‘‘Living with Gaucher Disease: A Guide for Patients,
Parents, Relatives, and Friends.’’ <http://neurowww3.mgh.harvard.edu/gaucher/living.html>.
National Foundation for Jewish Genetic Diseases
(NFJGD). <http://www.nfjgd.org/>.

Amy Vance, MS, CGC

Gay and lesbian health
Definition
Lesbian, gay, bisexual, and transgender (LGBT)
individuals are as diverse as the general population in
terms of race, ethnicity, age, religion, education,
income, and family history. A number of health concerns are unique to or shared by the LGBT community, however, including an increased risk of certain
cancers, infectious and sexually transmitted diseases
(STDs), and mental health disorders; issues relating
to nutrition and weight, tobacco use, and substance
abuse; and discrimination by health care and insurance
providers.

Description
The definitions of different sexual identities have
shifted over the years, as have the perceptions and
stereotypes of the general population. Because of the
wide range of behaviors and identities that exist in the
LGBT community, it is difficult to develop an inclusive definition. It is generally accepted, however, that
gay men and lesbians are sexually attracted to or
participate in sexual behaviors with individuals of
the same gender, while bisexual men and women are
sexually attracted to or participate in sexual behaviors
with individuals of both genders. Transgender individuals live part- or full-time in a gender role opposite to
their genetic sex.
It is estimated that approximately 2.8% of men
and 1.4% of women identify as being gay, lesbian, or
bisexual while 9.1% of men and 4.3% of women have
participated in sexual behavior with someone of the
same gender at least once. The true extent of the
transgender community has not been well researched
in the United States; one study from the Netherlands
in 1993 found that one in 11,900 males and one in
30,400 females are transgnder.
1572

There are a number of issues that arise when
trying to define sexual orientation. Many gay men
and lesbians have participated in or continue to
participate in sexual activities with members of the
opposite sex but choose not to identify as heterosexuals or bisexuals. Others have never participated
in sexual activities at all yet still identify as gay,
lesbian, or bisexual. Some men and women identifying as bisexuals are in long-term, monogamous relationships with individuals of the same or opposite
sex. Male-to-female (MTF) or female-to-male (FTM)
transgender individuals may or may not identify
themselves as gay or lesbian.
The implications of these identity issues are farreaching. Misdiagnoses or improper medical recommendations might come from health care providers
who have mistakenly assumed sexual behaviors or
risks from the patient’s stated identity. For example,
a provider might incorrectly assume that a lesbian
patient has never had sexual intercourse with a male
and therefore would not have contracted STDs not
normally transmitted by sexual activities between
women. It has been difficult to closely estimate the
numbers of LGBT individuals in the United States
because of varying definitions. Likewise, the statistics in medical or social studies and surveys on LGBT
issues might vary widely depending on what definitions were provided for the respondents. Because
of this, many researchers have opted for the more
inclusive terms of ‘‘men who have sex with men’’
(MSM) and ‘‘women who have sex with women’’
(WSW) to categorize gay, lesbian, and bisexual
respondents.
Important health care issues
Many LGBT individuals have difficulty revealing
their sexual identity (‘‘coming out’’) to their health
care providers. They may fear discrimination from
providers or believe that their confidentiality might
be breached. In some cases health care workers have
been poorly trained to address the needs of LGBT
individuals or have difficulty communicating with
their LGBT patient (one study indicated that 40% of
physicians are uncomfortable providing care for gay
or lesbian patients). In addition, many questions
posed in questionnaires or examinations are heterosexually biased (e.g. asking a lesbian which birth control methods she uses or a gay man if he is married,
single, or divorced).
Other reasons why LGBT individuals are often
hesitant to share their sexual identity are more logistical. Many insurance companies deny benefits to
long-term partners on the basis that they are not
GALE ENCYCLOPEDIA OF MEDICINE

Some of the health concerns and risk factors that
are relevant to LBGT individuals may be shared by the
general population, while others are more specific to
the LGBT community, and still others are specific
to different subgroups of LGBT individuals. These
health concerns may be grouped into the following
areas of concern:


Sexual behavior issues: STDs such as human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), hepatitis A virus (HAV),
hepatitis B virus (HBV), bacterial vaginosis, gonorrhea, chlamydia, and genital warts (human papillomavirus or HPV); anal, ovarian, and cervical
cancer.



Cultural issues: body image, nutrition, weight, and
eating disorders; drug and alcohol abuse; tobacco
use; parenting and family planning.



Discrimination issues: inadequate medical care; harassment at work, school, or home; difficulty in
obtaining housing, insurance coverage, or child custody; violence.



Sexual identity issues: conflicts with family, friends,
and work mates; psychological issues such as anxiety, depression, and suicide; economic hardship.

CANCER. Cancer is the second leading cause
of death in the United States. In 2000, it was estimated that 1,220,100 individuals were diagnosed
with cancer and 55,200 lost their lives as a result.
LBGT individuals are at an increased risk for certain
types of cancers. Some researchers believe that those
who do not disclose their sexual identity live with an
added stress that suppresses the immune system,
thus leaving them with an increased risk of tumor
growth.

Several studies have indicated that lesbians have
higher risk for developing breast cancer. This is partially related to higher rates of risk factors such as
obesity, alcohol use, tobacco use, and nulliparity (not
bearing children). It has also been shown that lesbians
are less likely to be screened for breast cancer than
heterosexual women. Lesbians also have additional
risk of developing ovarian cancer, due to inadequate
access to health care, nulliparity, and not using oral
GALE ENCYCLOPEDIA OF MEDICINE

contraceptives (use of oral contraceptives has been
shown to decrease the risk of getting ovarian cancer).
Gay and bisexual men (or more generally, men who
have sex with men [MSM]) are at higher risk of developing non-Hodgkin’s lymphoma, Hodgkin’s disease,
and anal cancer. Kaposi’s sarcoma, an AIDS-associated
cancer, used to be found in the gay community at rates
thousands of times more than the general population
before more effective antiretroviral drugs became available for people infected with HIV. Anal cancer is associated with transmission of human papillomavirus
(HPV); a 1998 study indicated 73% of HIV-positive
and 23% of HIV-negative MSM were infected with
more than one type of HPV. The risk factors associated
with MSM are also associated with increased rates of
anal cancer (i.e. smoking, having many sexual partners,
and receiving anal intercourse).
AIDS. As of 2001, more than 760,000 individuals
had been diagnosed with AIDS in the United States.
More than 80% are men; about 16% are women,
and 1% are children 12 years old or younger. In
2000, more than 30,000 MSM were diagnosed with
AIDS. While this number was down from 1999, it
remained the highest risk factor for the disease.
Other major risk groups associated with AIDS transmission include intravenous drug users (IDUs) who
share needles, heterosexuals who engage in high-risk
sexual behaviors, inmates at correctional facilities,
and neonates (newborns) whose mothers are infected
with HIV.

Gender identity disorder is defined as ‘‘a strong and
persistent cross-gender identification . . . manifested by
symptoms such as a stated desire to be the other sex,
frequently passing as the other sex, desire to live or be
treated as the other sex, or the conviction that he or she
as the typical feelings and reactions of the other sex’’
(DSM-IV, 302.85). Transvestic fetishism is defined as
involving ‘‘recurrent, intense sexually arousing fantasies, sexual urges, or behaviors involving cross-dressing’’
(DSM-IV, 302.3). Both disorders lead to a ‘‘disturbance
that causes clinically significant distress or impairment
in social, occupational, or other important areas of
functioning.’’ This last point iterates that transgender
individuals are not automatically considered under
DSM-IV to have a mental disorder.
NUTRITION AND WEIGHT. Diet and nutritional factors are associated with a number of diseases including
cancer, stroke, diabetes, heart disease, and osteoporosis.
It has been shown that lesbians are more likely than
heterosexual women to be obese, have a higher body
mass index (BMI), and have higher rates of smoking,
but are also more likely to have a healthier body image

1573

Gay and lesbian health

married. LGBT patients may have inadequate access
to health care, either because they live in a remote
rural area or in the crowded inner city. Some samesex partners encounter discrimination in hospitals and
clinics when they are denied the rights usually given to
spouses of a patient such as visiting, making medical
decisions, and participating in consultations with
physicians.

Gay and lesbian health



maintaining the strictest code of confidentiality

KEY TERMS



Nulliparity—The condition of being nulliparous, or
not bearing offspring.

developing and maintaining health care centers or
clinics that address LGBT-specific needs



asking non-threatening questions to determine if a
person is at risk of an STD



educating patients of risk factors associated with
STDs, possible vaccines, and treatments available



providing services to individuals in the process of
disclosing their sexual identity and, if applicable,
their families

(42% compared to 21% of heterosexual women). Gay
men and adolescents, on the other hand, have been
shown to have increased rates of eating disorder behaviors than heterosexual men; examples are binge eating
(25% compared to 11%), purging behaviors (12% to
4%), and poor body image (28% to 12%).
SUBSTANCE AND TOBACCO USE. Marijuana and

cocaine use has been shown to be higher among lesbians than heterosexual women. The incidence of the
use of some drugs is higher in gay men than heterosexual men; these include marijuana, psychedelic
drugs, ecstasy, barbituates, and stimulants such as
amyl or butyl nitrate (‘‘poppers’’). There is some indication that the use of some illicit drugs speeds up the
replication of HIV, although more research needs to
be done in this area.
Cigarette smoking is responsible for 430,000
deaths a year in the United States, with an estimated
3,000 nonsmokers dying as a result of exposure to secondhand smoke. In 2004 the rate of smoking among all
adults was 28%. In contrast, 50% of gay men, lesbians
and bisexuals were noted to be smokers. Lesbians are
more than two times as likely to become heavy smokers
than heterosexual women. Research shows that lesbians
have the toughest time giving up smoking. For many
years, efforts to improve health among the LGBT
population has focused on AIDS and STDs and smoking cessation has taken a back seat.

Prevention
There are numerous ways that health care providers can improve the access to and experience of
health care services for LGBT individuals. These
include:


rewording questionnaires and examinations to be
inclusive of LGBT patients



providing referrals to social service agencies and
counseling services that are LGBT-friendly



taking educational courses that are sensitive to the
needs of LGBT patients



treating the families of LGBT patients as one would
the families of heterosexual patients

1574

Resources
PERIODICALS

DuLong, Jessica. ‘‘Snuffing Out the Butts: Campaigns to
Convince Gay Men and Lesbians to Ditch Cigarettes
Tey to Cut Through a Long-held Addiction.’’ The
Advocate March 16, 2004: 30-32.
ORGANIZATIONS

Gay and Lesbian Medical Association. 459 Fulton Street,
Suite 107, San Francisco, CA 94102. (415) 225-4547.
<http://www.glma.org>.
Parents, Families, and Friends of Lesbians and Gays. 1726
M Street NW, Suite 400, Washington, DC 20036. (202)
467-8180. <http://www.pflag.org>.
OTHER

Albert, Sarah. ‘‘Lesbians and Gays More Likely to Smoke,
Survey Says.’’ GayHealth Website. May 16, 2001.
<http://www.gayhealth.com/templates/
99022445042572021484300001/news/
index.html?record=554>.
Dean, Laura, Ilan H. Meyer, Kevin Robinson, Randall L.
Sell, Robert Sember, Vincent M. B. Silenzio, Deborah
J. Bowen, Judith Bradford, Esther Rothblum, Jocelyn
White, Patricia Dunn, Ann Lawrence, Daniel Wolfe,
and Jessica Xavier. ‘‘Lesbian, Gay, Bisexual, and
Transgender Health: Findings and Concerns.’’ Journal
of the Gay and Lesbian Medical Association. October
2000. <http://www.glma.org/pub/jglma/vol4/3/
index.html>.
Garbo, Jon. ‘‘FDA Approves Combo Vaccine for Hepatitis
A and B.’’ GayHealth Website. May 14, 2001.
<http://www.gayhealth.com/templates/
99022462467343139648300002/news?
record=553>.
‘‘Healthy People 2010 Companion Document for
Lesbian, Gay, Bisexual, and Transgender (LGBT)
Health.’’ Gay and Lesbian Medical Association.
April 2001. <http://www.glma.org/policy/hp2010/
index.html>.

Stéphanie Dionne
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Definition
The psychological diagnosis gender identity
disorder (GID) is used to describe a male or female
that feels a strong identification with the opposite sex
and experiences considerable distress because of their
actual sex.

Description
Gender identity disorder can affect children,
adolescents, and adults. Individuals with gender
identity disorder have strong cross-gender identification. They believe that they are, or should be, the
opposite sex. They are uncomfortable with their sexual
role and organs and may express a desire to alter
their bodies. While not all persons with GID are
labeled as transsexuals, there are those who are determined to undergo sex change procedures or have done
so, and, therefore, are classified as transsexual. They
often attempt to pass socially as the opposite sex.
Transsexuals alter their physical appearance cosmetically and hormonally, and may eventually undergo
a sex-change operation.
Children with gender identity disorder refuse to
dress and act in sex-stereotypical ways. It is important to remember that many emotionally healthy
children experience fantasies about being a member
of the opposite sex. The distinction between these
children and gender identity disordered children is
that the latter experience significant interference in
functioning because of their cross-gender identification. They may become severely depressed, anxious,
or socially withdrawn.

Causes and symptoms
The cause of gender identity disorder is not
known. It has been theorized that a prenatal hormonal
imbalance may predispose individuals to the disorder.
Problems in the individual’s family interactions or
family dynamics have also been postulated as having
some causal impact.
The Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (DSM-IV), the diagnostic
reference standard for United States mental health
professionals, describes the criteria for gender identity
disorder as an individual’s strong and lasting crossgender identification and their persistent discomfort
with their biological gender role. This discomfort must

GALE ENCYCLOPEDIA OF MEDICINE

DSM-IV specifies that children must display
at least four of the following symptoms of crossgender identification for a diagnosis of gender identity
disorder:


a repeatedly stated desire to be, or insistence that he
or she is, the opposite sex



a preference for cross-dressing



a strong and lasting preference to play make-believe
and role-playing games as a member of the opposite
sex or persistent fantasies that he or she is the opposite sex



a strong desire to participate in the stereotypical
games of the opposite sex



a strong preference for friends and playmates of the
opposite sex

Diagnosis
Gender identity disorder is typically diagnosed
by a psychiatrist or psychologist, who conducts an
interview with the patient and takes a detailed social
history. Family members may also be interviewed during the assessment process. This evaluation usually
takes place in an outpatient setting.

Treatment
Treatment for children with gender identity disorder focuses on treating secondary problems such as
depression and anxiety, and improving self-esteem.
Treatment may also work on instilling positive identifications with the child’s biological gender. Children
typically undergo psychosocial therapy sessions; their
parents may also be referred for family or individual
therapy.
Transsexual adults often request hormone and
surgical treatments to suppress their biological sex
characteristics and acquire those of the opposite sex.
A team of health professionals, including the treating
psychologist or psychiatrist, medical doctors, and
several surgical specialists, oversee this transitioning
process. Because of the irreversible nature of the
surgery, candidates for sex-change surgery are evaluated extensively and are often required to spend a
period of time integrating themselves into the crossgender role before the procedure begins. Counseling
and peer support are also invaluable to transsexual
individuals.
1575

Gender identity disorder

Gender identity disorder

cause a significant amount of distress or impairment in
the functioning of the individual.

Gender reassignment surgery



Newborns with intersex deformities must early on be
assigned to one sex or the other. These deformities
represent intermediate stages between the primordial
female genitals and the change into male caused by
male hormone stimulation.



Both men and women occasionally believe they are
physically a different sex than they are mentally and
emotionally. This dissonance is so profound that
they are willing to be surgically altered. This condition is known as gender identity disorder; it is thought
to be more common in men than in women.

KEY TERMS
Cross-dressing—Dressing in clothing that is stereotypical of the opposite sex.
Gender identity disorder (GID)—A strong and lasting cross-gender identification and persistent discomfort with one’s biological gender (sex) role. This
discomfort must cause a significant amount of distress
or impairment in the functioning of the individual.
Transsexual—A person with gender identity disorder who has an overwhelming desire to change
anatomic sex; one who seeks hormonal or surgical
treatment to change sex.

Prognosis
Long-term follow up studies have shown positive
results for many transsexuals who have undergone sexchange surgery. However, significant social, personal,
and occupational issues may result from surgical sex
changes, and the patient may require psychotherapy or
counseling.
Resources
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry
(AACAP). 3615 Wisconsin Ave. NW, Washington, DC
20016. (202) 966-7300. <http://www.aacap.org>.
OTHER

The National Transgender Guide. <http://
www.tgguide.com>.

Paula Anne Ford-Martin

Gender reassignment surgery
Definition
Also known as sex change surgery or sex reassignment surgery, gender reassignment surgery is a procedure that changes a person’s external genital organs
from those of one gender to those of the other.

Purpose
There are two reasons commonly given for altering the genital organs:
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Although technical considerations in the case of
babies with ambiguous genitalia would seem to favor
surgical conversion to female structures rather than
to male, this conclusion has been challenged in the
early 2000s. William G. Reiner, a child and adolescent psychiatrist, undertook a study of 29 genetic
males who had been born with defective external
genitalia and reared as females following surgery.
He found that over half of them identified as males
by adolescence in spite of the absence of male genitalia. Dr. Reiner has concluded that psychosexual
development in genetic and hormonal males is heavily influenced by exposure to androgens prior to
birth, and has called for a reevaluation of the practice
of routinely assigning male babies with ambiguous
genitals to the female sex.

Precautions
Sexual identity is probably the most profound
characteristic humans have. Assigning it must take
place immediately after birth, both for the child’s
and the parents’ comfort. Changing sexual identity
may be the most significant change one can experience. It therefore should be done with every care
and caution. By the time most adults come to surgery, they have lived for many years with dissonant
identity. The average in one study was 29 years.
Nevertheless, even then they may not be fully aware
of the implications of becoming a member of the
other sex.
Gender identity disorder has been officially defined
by the American Psychiatric Associan in the fourth
edition of the Diagnostic and Statistical Manual of
Mental Disorders, or DSM-IV, as a condition in
which the affected individual has ‘‘a strong and persistent cross-gender identification’’ combined with ‘‘persistent discomfort about one’s assigned sex.’’ Because
of widespread social disapproval of surgical gender
reassignment, researchers do not know the true prevalence of gender identity disorders in the general population. Early estimates were 1:37,000 males and 1:107,000
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Description
Converting male to female anatomy requires
removal of the penis, reshaping genital tissue to appear
more female, and constructing a vagina. A vagina can
be successfully formed from a skin graft or an isolated
loop of intestine.
Female to male surgery has achieved lesser success, due to the difficulty of building a functioning
penis from the much smaller amount of erectile tissue
available in the female genitals. Penis construction is
not attempted less than a year after the preliminary
surgery to remove the female organs. One study in
Singapore found that a third of the patients would
not undergo the surgery again. Nevertheless, they
were all pleased with the change of sex. Besides the
genital organs, the breasts need to be surgically altered
for a more male appearance. This can be done quite
successfully.
Orgasm, or at least a reasonable degree of erogenous sensitivity, can be experienced by patients after
surgery.

KEY TERMS
Chromosomes—The carriers of genes, which
determine sex and characteristics.
Gender identity disorder (GID)—A mental disorder in which a person strongly identifies with
the other sex and feels uncomfortable with his or
her biological sex. It occurs more often in males
than in females.
gender reassignment surgery—The surgical alteration and reconstruction of a person’s sex organs
to resemble those of the other sex as closely as
possible. It is sometimes called gender reassignment
surgery.

There is some controversy as of the early 2000s
regarding the appropriateness of performing gender
reassignment surgery on adolescents, as opposed to
either infants or older adults, on the grounds that teenagers are often uncertain about many aspects of their
sexuality. The recent case of a thirteen-year-old girl who
requested gender reassignment surgery in Australia
reflects the intensity of this controversy among surgeons
as well as members of the general public.

Aftercare
Preparation
As of the early 2000s, patients requesting gender
reassignment surgery must undergo a lengthy process of
physical and psychological evaluation before receiving
approval for surgery. The Harry Benjamin International
Gender Dysphoria Association (HBIGDA), which is
presently the largest worldwide professional association
dealing with the treatment of gender identity disorders, has published standards of care that are followed by most surgeons who perform genital surgery
for gender reassignment. HBIGDA stipulates that a
patient must meet the diagnostic criteria for gender
identity disorders as defined by either the Diagnostic
and Statistical Manual of Mental Disorders, fourth
edition (DSM-IV) or the International Classification
of Diseases–10 (ICD-10).
Preparation for gender reassignment surgery
includes a period of several years of hormonal treatment to change the body contours, vocal pitch, patterns of facial and body hair, etc. to those of the other
sex. As the patient’s body and voice begin to change,
he or she is also asked to practice dressing and acting
as a member of that sex.
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Social support, particularly from the family, is
important for readjustment as a member of the opposite sex. If patients were socially or emotionally
unstable before the operation, over 30, or had an unsuitable body build for the new sex, they tend to do poorly.
Paul McHugh, the former head of the department of
psychiatry at Johns Hopkins University, has reported
that people who think that gender reassignment surgery
will solve all their emotional and social problems are
likely to be disappointed. ‘‘[These patients] had much
the same problems with relationships, work, and emotions as before. The hope that they would emerge now
from their emotional difficulties to flourish psychologically had not been fulfilled.’’

Risks
All surgery runs the risk of infection, bleeding,
and a need to return for repairs. This surgery is irreversible, so the patient must have no doubts about
accepting the results.
The most common physical complication of the
male to female surgery is narrowing of the new vagina.
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Gender reassignment surgery

females. A recent study in the Netherlands, however,
maintains that a more accurate estimation is 1:11,900
males and 1:30,400 females. In any case, the number of
surgical procedures is lower than the number of
patients diagnosed with gender identity disorders.

Gene therapy

There is some risk of patients developing other
mental disorders associated with their new sex. Several
cases of anorexia nervosa, an eating disorder that is far
more common in women than in men, have been
reported in males who underwent gender reassignment
surgery.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised. Washington,
DC: American Psychiatric Association, 2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychosexual Disorders.’’ Section 15, Chapter 192 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
PERIODICALS

McHugh, Paul, MD. ‘‘Surgical Sex.’’ First Things 147
(November 2004): 34–38.
Reiner, W. G., and J. P. Gearhart. ‘‘Discordant Sexual
Identity in Some Genetic Males with Cloacal Exstrophy
Assigned to Female Sex at Birth.’’ New England Journal
of Medicine 350 (January 22, 2004): 333–341.
Reiner, W. G. ‘‘Psychosexual Development in Genetic
Males Assigned Female: The Cloacal Exstrophy
Experience.’’ Child and Adolescent Psychiatry Clinics of
North America 13 (July 2004): 657–674.
Spriggs, M. P. ‘‘Ethics and the Proposed Treatment for a
13-Year-Old with Atypical Gender Identity.’’ Medical
Journal of Australia 181 (September 20, 2004): 319–321.
Winston, A. P., S. Acharya, S. Chaudhuri, and L. Fellowes.
‘‘Anorexia Nervosa and Gender Identity Disorder in
Biologic Males: A Report of Two Cases.’’ International
Journal of Eating Disorders 36 (July 2004): 109–113.
ORGANIZATIONS

American Board of Urology (ABU). 2216 Ivy Road, Suite
210, Charlottesville, VA 22903. (434) 979-0059.
<http://www.abu.org>.
American Psychiatric Association (APA). 1400 K Street,
NW, Washington, DC 20005. (888) 357-7924. <http://
www.psych.org>.
Harry Benjamin International Gender Dysphoria
Association, Inc. (HBIGDA). 1300 South Second
Street, Suite 180, Minneapolis, MN 55454. (612) 6251500. <http://www.hbigda.org>.
OTHER

Harry Benjamin International Gender Dysphoria
Association (HBIGDA). Standards of Care for Gender
Identity Disorders, 6th version. February 2001. <http://
www.hbigda.org/socv6.html>.

J. Ricker Polsdorfer, MD
Rebecca J. Frey, PhD
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Gene therapy
Gene therapy is a rapidly growing field of medicine in which genes are introduced into the body to
treat diseases. Genes control heredity and provide the
basic biological code for determining a cell’s specific
functions. Gene therapy seeks to provide genes that
correct or supplant the disease-controlling functions
of cells that are not, in essence, doing their job.
Somatic gene therapy introduces therapeutic genes at
the tissue or cellular level to treat a specific individual.
Germ-line gene therapy inserts genes into reproductive cells or possibly into embryos to correct genetic
defects that could be passed on to future generations.
Initially conceived as an approach for treating inherited diseases, like cystic fibrosis and Huntington’s disease, the scope of potential gene therapies has grown
to include treatments for cancers, arthritis, and infectious diseases. Although gene therapy testing in
humans has advanced rapidly, many questions surround its use. For example, some scientists are concerned that the therapeutic genes themselves may
cause disease. Others fear that germ-line gene therapy
may be used to control human development in ways
not connected with disease, like intelligence or
appearance.

The biological basis of gene therapy
Gene therapy has grown out of the science of
genetics or how heredity works. Scientists know that
life begins in a cell, the basic building block of all
multicellular organisms. Humans, for instance, are
made up of trillions of cells, each performing a specific
function. Within the cell’s nucleus (the center part of a
cell that regulates its chemical functions) are pairs of
chromosomes. These threadlike structures are made
up of a single molecule of DNA (deoxyribonucleic
acid), which carries the blueprint of life in the form
of codes, or genes, that determine inherited
characteristics.
A DNA molecule looks like two ladders with one
of the sides taken off both and then twisted around
each other. The rungs of these ladders meet (resulting
in a spiral staircase-like structure) and are called base
pairs. Base pairs are made up of nitrogen molecules
and arranged in specific sequences. Millions of these
base pairs, or sequences, can make up a single gene,
specifically defined as a segment of the chromosome
and DNA that contains certain hereditary information. The gene, or combination of genes formed by
these base pairs ultimately direct an organism’s
growth and characteristics through the production of
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Scientists have long known that alterations in
genes present within cells can cause inherited diseases
like cystic fibrosis, sickle-cell anemia, and hemophilia.
Similarly, errors in the total number of chromosomes
can cause conditions such as Down syndrome or
Turner’s syndrome. As the study of genetics advanced,
however, scientists learned that an altered genetic
sequence also can make people more susceptible to
diseases, like atherosclerosis, cancer, and even schizophrenia. These diseases have a genetic component, but
also are influenced by environmental factors (like diet
and lifestyle). The objective of gene therapy is to treat
diseases by introducing functional genes into the body
to alter the cells involved in the disease process by
either replacing missing genes or providing copies of
functioning genes to replace nonfunctioning ones. The
inserted genes can be naturally-occurring genes that
produce the desired effect or may be genetically engineered (or altered) genes.
Scientists have known how to manipulate a gene’s
structure in the laboratory since the early 1970s through
a process called gene splicing. The process involves
removing a fragment of DNA containing the specific
genetic sequence desired, then inserting it into the DNA
of another gene. The resultant product is called recombinant DNA and the process is genetic engineering.
There are basically two types of gene therapy.
Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) or someday possibly
into embryos in hopes of correcting genetic abnormalities that could be passed on to future generations.
Most of the current work in applying gene therapy,
however, has been in the realm of somatic gene therapy. In this type of gene therapy, therapeutic genes are
inserted into tissue or cells to produce a naturally
occurring protein or substance that is lacking or not
functioning correctly in an individual patient.

Viral vectors
In both types of therapy, scientists need something
to transport either the entire gene or a recombinant
DNA to the cell’s nucleus, where the chromosomes
and DNA reside. In essence, vectors are molecular
delivery trucks. One of the first and most popular vectors developed were viruses because they invade cells as
part of the natural infection process. Viruses have the
potential to be excellent vectors because they have a
specific relationship with the host in that they colonize
certain cell types and tissues in specific organs. As a
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result, vectors are chosen according to their attraction
to certain cells and areas of the body.
One of the first vectors used was retroviruses.
Because these viruses are easily cloned (artificially
reproduced) in the laboratory, scientists have studied
them extensively and learned a great deal about their
biological action. They also have learned how to
remove the genetic information that governs viral
replication, thus reducing the chances of infection.
Retroviruses work best in actively dividing cells,
but cells in the body are relatively stable and do not
divide often. As a result, these cells are used primarily
for ex vivo (outside the body) manipulation. First, the
cells are removed from the patient’s body, and the
virus, or vector, carrying the gene is inserted into
them. Next, the cells are placed into a nutrient culture
where they grow and replicate. Once enough cells are
gathered, they are returned to the body, usually by
injection into the blood stream. Theoretically, as
long as these cells survive, they will provide the desired
therapy.
Another class of viruses, called the adenoviruses,
also may prove to be good gene vectors. These viruses
can effectively infect nondividing cells in the body,
where the desired gene product then is expressed naturally. In addition to being a more efficient approach to
gene transportation, these viruses, which cause
respiratory infections, are more easily purified and
made stable than retroviruses, resulting in less chance
of an unwanted viral infection. However, these viruses
live for several days in the body, and some concern
surrounds the possibility of infecting others with the
viruses through sneezing or coughing. Other viral vectors include influenza viruses, Sindbis virus, and a
herpes virus that infects nerve cells.
Scientists also have delved into nonviral vectors.
These vectors rely on the natural biological process in
which cells uptake (or gather) macromolecules. One
approach is to use liposomes, globules of fat produced
by the body and taken up by cells. Scientists also are
investigating the introduction of raw recombinant
DNA by injecting it into the bloodstream or placing it
on microscopic beads of gold shot into the skin with a
‘‘gene-gun.’’ Another possible vector under development is based on dendrimer molecules. A class of polymers (naturally occurring or artificial substances that
have a high molecular weight and formed by smaller
molecules of the same or similar substances), is ‘‘constructed’’ in the laboratory by combining these smaller
molecules. They have been used in manufacturing
Styrofoam, polyethylene cartons, and Plexiglass. In
the laboratory, dendrimers have shown the ability to
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Gene therapy

certain chemicals, primarily proteins, which carry out
most of the body’s chemical functions and biological
reactions.

Gene therapy

transport genetic material into human cells. They also
can be designed to form an affinity for particular cell
membranes by attaching to certain sugars and protein
groups.

The history of gene therapy
In the early 1970s, scientists proposed ‘‘gene surgery’’ for treating inherited diseases caused by faulty
genes. The idea was to take out the disease-causing
gene and surgically implant a gene that functioned
properly. Although sound in theory, scientists, then
and now, lack the biological knowledge or technical
expertise needed to perform such a precise surgery in
the human body.
However, in 1983, a group of scientists from
Baylor College of Medicine in Houston, Texas, proposed that gene therapy could one day be a viable
approach for treating Lesch-Nyhan disease, a rare
neurological disorder. The scientists conducted experiments in which an enzyme-producing gene (a specific
type of protein) for correcting the disease was injected
into a group of cells for replication. The scientists
theorized the cells could then be injected into people
with Lesch-Nyhan disease, thus correcting the genetic
defect that caused the disease.
As the science of genetics advanced throughout
the 1980s, gene therapy gained an established foothold
in the minds of medical scientists as a promising
approach to treatments for specific diseases. One of
the major reasons for the growth of gene therapy was
scientists’ increasing ability to identify the specific
genetic malfunctions that caused inherited diseases.
Interest grew as further studies of DNA and chromosomes (where genes reside) showed that specific
genetic abnormalities in one or more genes occurred
in successive generations of certain family members
who suffered from diseases like intestinal cancer, bipolar disorder, Alzheimer’s disease, heart disease, diabetes, and many more. Although the genes may not
be the only cause of the disease in all cases, they may
make certain individuals more susceptible to developing the disease because of environmental influences,
like smoking, pollution, and stress. In fact, some scientists theorize that all diseases may have a genetic
component.
On September 14, 1990, a four-year old girl suffering from a genetic disorder that prevented her body
from producing a crucial enzyme became the first
person to undergo gene therapy in the United States.
Because her body could not produce adenosine deaminase (ADA), she had a weakened immune system, making her extremely susceptible to severe, life-threatening
1580

infections. W. French Anderson and colleagues at the
National Institutes of Health’s Clinical Center in
Bethesda, Maryland, took white blood cells (which are
crucial to proper immune system functioning) from the
girl, inserted ADA producing genes into them, and then
transfused the cells back into the patient. Although the
young girl continued to show an increased ability to
produce ADA, debate arose as to whether the improvement resulted from the gene therapy or from an additional drug treatment she received.
Nevertheless, a new era of gene therapy began as
more and more scientists sought to conduct clinical
trial (testing in humans) research in this area. In that
same year, gene therapy was tested on patients suffering from melanoma (skin cancer). The goal was to help
them produce antibodies (disease fighting substances
in the immune system) to battle the cancer.
These experiments have spawned an ever growing
number of attempts at gene therapies designed to perform a variety of functions in the body. For example, a
gene therapy for cystic fibrosis aims to supply a gene
that alters cells, enabling them to produce a specific
protein to battle the disease. Another approach was
used for brain cancer patients, in which the inserted
gene was designed to make the cancer cells more likely
to respond to drug treatment. Another gene therapy
approach for patients suffering from artery blockage,
which can lead to strokes, induces the growth of new
blood vessels near clogged arteries, thus ensuring normal blood circulation.
Currently, there are a host of new gene therapy
agents in clinical trials. In the United States, both
nucleic acid based (in vivo) treatments and cell-based
(ex vivo) treatments are being investigated. Nucleic
acid based gene therapy uses vectors (like viruses) to
deliver modified genes to target cells. Cell-based gene
therapy techniques remove cells from the patient in
order to genetically alter them then reintroduce them
to the patient’s body. Presently, gene therapies for the
following diseases are being developed: cystic fibrosis
(using adenoviral vector), HIV infection (cell-based),
malignant melanoma (cell-based), Duchenne muscular
dystrophy (cell-based), hemophilia B (cell-based), kidney cancer (cell-based), Gaucher’s Disease (retroviral
vector), breast cancer (retroviral vector), and lung
cancer (retroviral vector). When a cell or individual
is treated using gene therapy and successful incorporation of engineered genes has occurred, the cell or individual is said to be transgenic.
The medical establishment’s contribution to
transgenic research has been supported by increased
government funding. In 1991, the U.S. government
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Gene therapy
Early detection of cancer. The researcher’s pen marks a band on a DNA sequencing autoradiogram confirming a bladder cancer.
(Custom Medical Stock Photo. Reproduced by permission.)

provided $58 million for gene therapy research, with
increases in funding of $15-40 million dollars a year
over the following four years. With fierce competition
over the promise of societal benefit in addition to huge
profits, large pharmaceutical corporations have
moved to the forefront of transgenic research. In an
effort to be first in developing new therapies, and
armed with billions of dollars of research funds, such
corporations are making impressive strides toward
making gene therapy a viable reality in the treatment
of once elusive diseases.

Diseases targeted for treatment by gene
therapy
The potential scope of gene therapy is enormous.
More than 4,200 diseases have been identified as resulting directly from abnormal genes, and countless others
that may be partially influenced by a person’s genetic
makeup. Initial research has concentrated on developing gene therapies for diseases whose genetic origins
have been established and for other diseases that can
be cured or improved by substances genes produce.
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The following are examples of potential gene
therapies. People suffering from cystic fibrosis lack a
gene needed to produce a salt-regulating protein. This
protein regulates the flow of chloride into epithelial
cells, (the cells that line the inner and outer skin layers)
that cover the air passages of the nose and lungs.
Without this regulation, patients with cystic fibrosis
build up a thick mucus that makes them prone to lung
infections. A gene therapy technique to correct this
abnormality might employ an adenovirus to transfer
a normal copy of what scientists call the cystic fibrosis
transmembrane conductance regulator, or CTRF,
gene. The gene is introduced into the patient by spraying it into the nose or lungs. Researchers announced in
2004 that they had, for the first time, treated a dominant neurogenerative disease called Spinocerebella
ataxia type 1, with gene therapy. This could lead to
treating similar diseases such as Huntington s disease.
They also announced a single intravenous injection
could deliver therapy to all muscles, perhaps providing
hope to people with muscular dystrophy.
Familial hypercholesterolemia (FH) also is an
inherited disease, resulting in the inability to process
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Gene therapy

cholesterol properly, which leads to high levels of
artery-clogging fat in the blood stream. Patients with
FH often suffer heart attacks and strokes because of
blocked arteries. A gene therapy approach used to
battle FH is much more intricate than most gene
therapies because it involves partial surgical removal
of patients’ livers (ex vivo transgene therapy).
Corrected copies of a gene that serve to reduce cholesterol build-up are inserted into the liver sections,
which then are transplanted back into the patients.
Gene therapy also has been tested on patients with
AIDS. AIDS is caused by the human immunodeficiency
virus (HIV), which weakens the body’s immune system
to the point that sufferers are unable to fight off diseases like pneumonias and cancer. In one approach,
genes that produce specific HIV proteins have been
altered to stimulate immune system functioning without causing the negative effects that a complete HIV
molecule has on the immune system. These genes are
then injected in the patient’s blood stream. Another
approach to treating AIDS is to insert, via white
blood cells, genes that have been genetically engineered
to produce a receptor that would attract HIV and
reduce its chances of replicating. In 2004, researchers
reported that had developed a new vaccine concept for
HIV, but the details were still in development.
Several cancers also have the potential to be treated with gene therapy. A therapy tested for melanoma,
or skin cancer, involves introducing a gene with an
anticancer protein called tumor necrosis factor (TNF)
into test tube samples of the patient’s own cancer cells,
which are then reintroduced into the patient. In brain
cancer, the approach is to insert a specific gene that
increases the cancer cells’ susceptibility to a common
drug used in fighting the disease. In 2003, researchers
reported that they had harnessed the cell killing properties of adenoviruses to treat prostate cancer. A 2004
report said that researchers had developed a new
DNA vaccine that targeted the proteins expressed in
cervical cancer cells.

initiates a natural healing process that produces too
many cells in the artery and results in restenosis, or
reclosing of the artery. The gene therapy approach to
preventing this unwanted side effect is to cover the
outside of the stents with a soluble gel. This gel contains vectors for genes that reduce this overactive healing response.
Regularly throughout the past decade, and no
doubt over future years, scientists have and will come
up with new possible ways for gene therapy to help
treat human disease. Recent advancements include the
possibility of reversing hearing loss in humans with
experimental growing of new sensory cells in adult
guinea pigs, and avoiding amputation in patients with
severe circulatory problems in their legs with angiogenic growth factors.

The Human Genome Project
Although great strides have been made in gene
therapy in a relatively short time, its potential usefulness has been limited by lack of scientific data concerning the multitude of functions that genes control
in the human body. For instance, it is now known that
the vast majority of genetic material does not store
information for the creation of proteins, but rather is
involved in the control and regulation of gene expression, and is, thus, much more difficult to interpret.
Even so, each individual cell in the body carries thousands of genes coding for proteins, with some estimates as high as 150,000 genes. For gene therapy to
advance to its full potential, scientists must discover
the biological role of each of these individual genes
and where the base pairs that make them up are
located on DNA.

Gaucher disease is an inherited disease caused by a
mutant gene that inhibits the production of an enzyme
called glucocerebrosidase. Patients with Gaucher disease have enlarged livers and spleens and eventually
their bones deteriorate. Clinical gene therapy trials
focus on inserting the gene for producing this enzyme.

To address this issue, the National Institutes of
Health initiated the Human Genome Project in 1990.
Led by James D. Watson (one of the co-discoverers of
the chemical makeup of DNA) the project’s 15-year
goal is to map the entire human genome (a combination of the words gene and chromosomes). A genome
map would clearly identify the location of all genes as
well as the more than three billion base pairs that make
them up. With a precise knowledge of gene locations
and functions, scientists may one day be able to conquer or control diseases that have plagued humanity
for centuries.

Gene therapy also is being considered as an approach to solving a problem associated with a surgical
procedure known as balloon angioplasty. In this procedure, a stent (in this case, a type of tubular scaffolding) is used to open the clogged artery. However, in
response to the trauma of the stent insertion, the body

Scientists participating in the Human Genome
Project identified an average of one new gene a day,
but many expected this rate of discovery to increase.
By the year 2005, their goal was to determine the exact
location of all the genes on human DNA and the exact
sequence of the base pairs that make them up. Some of

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The future of gene therapy
Gene therapy seems elegantly simple in its concept: supply the human body with a gene that can
correct a biological malfunction that causes a disease.
However, there are many obstacles and some distinct
questions concerning the viability of gene therapy. For
example, viral vectors must be carefully controlled lest
they infect the patient with a viral disease. Some vectors, like retroviruses, also can enter cells functioning
properly and interfere with the natural biological processes, possibly leading to other diseases. Other viral
vectors, like the adenoviruses, often are recognized
and destroyed by the immune system so their therapeutic effects are short-lived. Maintaining gene
expression so it performs its role properly after vector
delivery is difficult. As a result, some therapies need to
be repeated often to provide long-lasting benefits.
One of the most pressing issues, however, is gene
regulation. Genes work in concert to regulate their
functioning. In other words, several genes may play a
part in turning other genes on and off. For example,
certain genes work together to stimulate cell division
and growth, but if these are not regulated, the inserted
genes could cause tumor formation and cancer.
Another difficulty is learning how to make the gene
go into action only when needed. For the best and
safest therapeutic effort, a specific gene should turn
on, for example, when certain levels of a protein or
enzyme are low and must be replaced. But the gene
also should remain dormant when not needed to
ensure it doesn’t oversupply a substance and disturb
the body’s delicate chemical makeup.
One approach to gene regulation is to attach other
genes that detect certain biological activities and then
react as a type of automatic off-and-on switch that
regulates the activity of the other genes according to
biological cues. Although still in the rudimentary
stages, researchers are making headway in inhibiting
some gene functioning by using a synthetic DNA to
block gene transcriptions (the copying of genetic information). This approach may have implications for
gene therapy.
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The ethics of gene therapy
While gene therapy holds promise as a revolutionary approach to treating disease, ethical concerns over
its use and ramifications have been expressed by scientists and lay people alike. For example, since much
needs to be learned about how these genes actually
work and their long-term effect, is it ethical to test
these therapies on humans, where they could have a
disastrous result? As with most clinical trials concerning new therapies, including many drugs, the patients
participating in these studies usually have not
responded to more established therapies and often
are so ill the novel therapy is their only hope for
long-term survival.
Another questionable outgrowth of gene therapy
is that scientists could possibly manipulate genes to
genetically control traits in human offspring that are
not health related. For example, perhaps a gene could
be inserted to ensure that a child would not be bald, a
seemingly harmless goal. However, what if genetic
manipulation was used to alter skin color, prevent
homosexuality, or ensure good looks? If a gene is
found that can enhance intelligence of children who
are not yet born, will everyone in society, the rich and
the poor, have access to the technology or will it be so
expensive only the elite can afford it?
The Human Genome Project, which plays such an
integral role for the future of gene therapy, also has
social repercussions. If individual genetic codes can be
determined, will such information be used against
people? For example, will someone more susceptible
to a disease have to pay higher insurance premiums or
be denied health insurance altogether? Will employers
discriminate between two potential employees, one
with a ‘‘healthy’’ genome and the other with genetic
abnormalities?
Some of these concerns can be traced back to the
eugenics movement popular in the first half of the
twentieth century. This genetic ‘‘philosophy’’ was a
societal movement that encouraged people with ‘‘positive’’ traits to reproduce while those with less desirable
traits were sanctioned from having children. Eugenics
was used to pass strict immigration laws in the United
States, barring less suitable people from entering the
country lest they reduce the quality of the country’s
collective gene pool. Probably the most notorious
example of eugenics in action was the rise of Nazism
in Germany, which resulted in the Eugenic Sterilization
Law of 1933. The law required sterilization for those
suffering from certain disabilities and even for some
who were simply deemed ‘‘ugly.’’ To ensure that this
novel science is not abused, many governments have
1583

Gene therapy

the genes identified through this project include a gene
that predisposes people to obesity, one associated with
programmed cell death (apoptosis), a gene that guides
HIV viral reproduction, and the genes of inherited
disorders like Huntington’s disease, Lou Gehrig’s disease, and some colon and breast cancers. In April
2003, the finished sequence was announced, with
99% of the human genome’s gene-containing regions
mapped to an accuracy of 99.9%.

Gene therapy

KEY TERMS
Cell—The smallest living unit of the body that groups
together to form tissues and help the body perform
specific functions.
Chromosome—A microscopic thread-like structure
found within each cell of the body, consisting of a
complex of proteins and DNA. Humans have 46
chromosomes arranged into 23 pairs. Changes in
either the total number of chromosomes or their
shape and size (structure) may lead to physical or
mental abnormalities.
Clinical trial—The testing of a drug or some other
type of therapy in a specific population of patients.
Clone—A cell or organism derived through asexual
(without sex) reproduction containing the identical
genetic information of the parent cell or organism.
Deoxyribonucleic acid (DNA)—The genetic material in cells that holds the inherited instructions for
growth, development, and cellular functioning.
Embryo—The earliest stage of development of a
human infant, usually used to refer to the first eight
weeks of pregnancy. The term fetus is used from
roughly the third month of pregnancy until delivery.
Enzyme—A protein that causes a biochemical reaction or change without changing its own structure or
function.
Eugenics—A social movement in which the population of a society, country, or the world is to be
improved by controlling the passing on of hereditary
information through mating.

protein, and is made up of a molecular sequence
found on a section of DNA. Each gene is found on a
precise location on a chromosome.
Gene transcription—The process by which genetic
information is copied from DNA to RNA, resulting in
a specific protein formation.
Genetic engineering—The manipulation of genetic
material to produce specific results in an organism.
Genetics—The study of hereditary traits passed on
through the genes.
Germ-line gene therapy—The introduction of genes
into reproductive cells or embryos to correct inherited genetic defects that can cause disease.
Liposome—Fat molecule made up of layers of lipids.
Macromolecules—A large molecule composed of
thousands of atoms.
Nitrogen—A gaseous element that makes up the base
pairs in DNA.
Nucleus—The central part of a cell that contains
most of its genetic material, including chromosomes
and DNA.
Protein—Important building blocks of the body,
composed of amino acids, involved in the formation
of body structures and controlling the basic functions
of the human body.
Somatic gene therapy—The introduction of genes
into tissue or cells to treat a genetic related disease
in an individual.

Gene—A building block of inheritance, which contains the instructions for the production of a particular

Vectors—Something used to transport genetic information to a cell.

established organizations specifically for overseeing the
development of gene therapy. In the United States, the
Food and Drug Administration (FDA) and the
National Institutes of Health require scientists to take
a precise series of steps and meet stringent requirements
before proceeding with clinical trials. As of mid-2004,
more than 300 companies were carrying out gene medicine developments and 500 clinical trials were underway. How to deliver the therapy is the key to unlocking
many of the researchers discoveries.

substantially change society. Despite the health and
ethical questions surrounding gene therapy, the field
will continue to grow and is likely to change medicine
faster than any previous medical advancement.

In fact, gene therapy has been immersed in more
controversy and surrounded by more scrutiny in both
the health and ethical arena than most other technologies (except, perhaps, for cloning) that promise to
1584

Resources
PERIODICALS

Abella, Harold. ‘‘Gene Therapy May Save Limbs.’’
Diagnostic Imaging (May 1, 2003): 16.
Christensen R. ‘‘Cutaneous Gene Therapy—An Update.’’
Histochemical Cell Biology (January 2001): 73-82.
‘‘Gene Therapy Important Part of Cancer Research.’’
Cancer Gene Therapy Week (June 30, 2003): 12.
‘‘Initial Sequencing and Analysis of the Human Genome.’’
Nature (February 15, 2001): 860-921.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

National Human Genome Research Institute. The
National Institutes of Health. 9000 Rockville Pike,
Bethesda, MD 20892. (301) 496-2433. <http://
www.nhgri.nih.gov>.
OTHER

Online Mendelian Inheritance in Man. Online genetic testing
information sponsored by National Center for
Biotechnology Information. <http://www.ncbi.nlm
.nih.gov/Omim/>.

Katherine S. Hunt, MS
Teresa G. Odle

General adaptation syndrome
Definition
General adaptation syndrome, or GAS, is a term
used to describe the body’s short-term and long-term
reactions to stress.
Stressors in humans include such physical stressors as starvation, being hit by a car, or suffering
through severe weather. Additionally, humans can
suffer such emotional or mental stressors as the loss
of a loved one, the inability to solve a problem, or even
having a difficult day at work.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Originally described by Hans Selye (1907–1982), an
Austrian-born physician who emigrated to Canada in
1939, the general adaptation syndrome represents a
three-stage reaction to stress. Selye explained his choice
of terminology as follows: ‘‘I call this syndrome general
because it is produced only by agents which have a
general effect upon large portions of the body. I call it
adaptive because it stimulates defense. . . . I call it a syndrome because its individual manifestations are coordinated and even partly dependent upon each other.’’
Selye thought that the general adaptation syndrome involved two major systems of the body, the
nervous system and the endocrine (or hormonal) system. He then went on to outline what he considered as
three distinctive stages in the syndrome’s evolution. He
called these stages the alarm reaction (AR), the stage of
resistance (SR), and the stage of exhaustion (SE).
Stage 1: Alarm reaction (AR)
The first stage of the general adaptation stage, the
alarm reaction, is the immediate reaction to a stressor.
In the initial phase of stress, humans exhibit a ‘‘fight or
flight’’ response, which prepares the body for physical
activity. However, this initial response can also decrease
the effectiveness of the immune system, making persons
more susceptible to illness during this phase.
Stage 2: Stage of resistance (SR)
Stage 2 might also be named the stage of adaptation, instead of the stage of resistance. During this
phase, if the stress continues, the body adapts to the
stressors it is exposed to. Changes at many levels take
place in order to reduce the effect of the stressor. For
example, if the stressor is starvation (possibly due to
anorexia), the person might experienced a reduced
desire for physical activity to conserve energy, and the
absorption of nutrients from food might be maximized.
Stage 3: Stage of exhaustion (SE)
At this stage, the stress has continued for some
time. The body’s resistance to the stress may gradually
be reduced, or may collapse quickly. Generally, this
means the immune system, and the body’s ability to
resist disease, may be almost totally eliminated.
Patients who experience long-term stress may succumb to heart attacks or severe infection due to their
reduced immunity. For example, a person with a
stressful job may experience long-term stress that
might lead to high blood pressure and an eventual
heart attack.
1585

General adaptation syndrome

Kingsman, Alan. ‘‘Gene Therapy Moves On.’’
SCRIP World Pharmaceutical News (July 7, 2004):
19:ndash;21.
Nevin, Norman. ‘‘What Has Happened to Gene Therapy?’’
European Journal of Pediatrics (2000): S240-S242.
‘‘New DNA Vaccine Targets Proteins Expressed in Cervical
Cancer Cells.’’ Gene Therapy Weekly (September 9,
2004): 14.
‘‘New Research on the Progress of Gene Therapy Presented
at Meeting.’’ Obesity, Fitness & Wellness Week (July 3,
2004): 405.
Pekkanen, John. ‘‘Genetics: Medicine’s Amazing Leap.’’
Readers Digest (September 1991): 23-32.
Silverman, Jennifer, and Steve Perlstein. ‘‘Genome
Project Completed.’’ Family Practice News (May 15,
2003): 50-51.
‘‘Study Highlights Potential Danger of Gene Therapy.’’
Drug Week (June 20, 2003): 495.
‘‘Study May Help Scientists Develop Safer Mthods for Gene
Therapy.’’ AIDS Weekly (June 30, 2003): 32.
Trabis, J. ‘‘With Gene Therapy, Ears Grow New Sensory
Cells.’’ Science News (June 7, 2003): 355.

General adaptation syndrome

Stress, a useful reaction?
The reader should note that Dr. Selye did not regard
stress as a purely negative phenomenon; in fact, he frequently pointed out that stress is not only an inevitable
part of life but results from intense joy or pleasure as well
as fear or anxiety. ‘‘Stress is not even necessarily bad for
you; it is also the spice of life, for any emotion, any
activity, causes stress.’’ Some later researchers have
coined the term ‘‘eustress’’ or pleasant stress, to reflect
the fact that such positive experiences as a job promotion, completing a degree or training program, marriage,
travel, and many others are also stressful.
Selye also pointed out that human perception of and
response to stress is highly individualized; a job or sport
that one person finds anxiety-provoking or exhausting
might be quite appealing and enjoyable to someone else.
Looking at one’s responses to specific stressors can contribute to better understanding of one’s particular physical, emotional, and mental resources and limits.

Causes and symptoms
Stress is one cause of general adaptation syndrome.
The results of unrelieved stress can manifest as fatigue,
irritability, difficulty concentrating, and difficulty
sleeping. Persons may also experience other symptoms
that are signs of stress. Persons experiencing unusual
symptoms, such as hair loss, without another medical
explanation might consider stress as the cause.
The general adaptation syndrome is also influenced by such universal human variables as overall
health and nutritional status, sex, age, ethnic or racial
background, level of education, socioeconomic status
(SES), genetic makeup, etc. Some of these variables are
biologically based and difficult or impossible to change.
For example, recent research indicates that men and
women respond somewhat differently to stress, with
women being more likely to use what is called the
‘‘tend and befriend’’ response rather than the classical
‘‘fight or flight’’ pattern. These researchers note that
most of the early studies of the effects of stress on the
body were conducted with only male subjects.
Selye’s observation that people vary in their perceptions of stressors was reflected in his belief that the
stressors themselves are less dangerous to health than
people’s maladaptive responses to them. He categorized certain diseases, ranging from cardiovascular
disorders to inflammatory diseases and mental disorders as ‘‘diseases of adaptation,’’ regarding them
as ‘‘largely due to errors in our adaptaive response to
stress’’ rather than the direct result of such outside
factors as germs, toxic substances, etc.
1586

Diagnosis
GAS by itself is not an official diagnostic category
but rather a descriptive term. A person who consults a
doctor for a stress-related physical illness may be
scheduled for blood or urine tests to measure the
level of cortisol or other stress-related hormones in
their body, or imaging studies to evaluate possible
abnormalities in their endocrine glands if the doctor
thinks that these tests may help to establish or confirm
a diagnosis.
The American Psychiatric Association (APA)
recognizes stress as a factor in anxiety disorders, particularly post-traumatic stress disorder (PTSD) and
acute stress disorder (ASD). These two disorders are
defined as symptomatic reactions to extreme traumatic stressors (war, natural or transportation disasters, criminal assault, abuse, hostage situations, etc.)
and differ chiefly in the time frame in which the symptoms develop. The APA also has a diagnostic category
of adjustment disorders, which are characterized either
by excessive reactions to stressors within the normal
range of experience (e.g. academic examinations, relationship breakups, being fired from a job) or by significant impairment in the person’s occupational or
social functioning.

Treatment
Treatment of stress-related illnesses typically
involves one or more stress reduction strategies. Stress
reduction strategies generally fall into one of three categories: avoiding stressors; changing one’s reaction to
the stressor(s); or relieving stress after the reaction to
the stressor(s). Many mainstream as well as complementary or alternative (CAM) strategies for stress
reduction, such as exercising, listening to music, aromatherapy, and massage relieve stress after it occurs.
Many psychotherapeutic approaches attempt to
modify the patient’s reactions to stressors. These
approaches often include an analysis of the patient’s
individual patterns of response to stress; for example,
one commonly used set of categories describes people
as ‘‘speed freaks,’’ ‘‘worry warts,’’ ‘‘cliff walkers,’’
‘‘loners,’’ ‘‘basket cases,’’ and ‘‘drifters.’’ Each pattern
has a recommended set of skills that the patient is
encouraged to work on; for example, worry warts are
advised to reframe their anxieties and then identify
their core values and goals in order to take concrete
action about their worries. In general, persons wishing
to improve their management of stress should begin by
consulting a medical professional with whom they feel
comfortable to discuss which option, or combination
of options, they can use.
GALE ENCYCLOPEDIA OF MEDICINE

Adjustment disorder—A disorder defined by the
development of significant emotional or behavioral
symptoms in response to a stressful event or series of
events within the normal range of human experience.
Cortisol—A steroid hormone released by the cortex
(outer portion) of the adrenal gland when a person
is under stress.
Eustress—A term that is sometimes used to refer to
positive stress.
Stress management—A set of techniques and programs intended to help people deal more effectively with stress in their lives by analyzing the
specific stressors and taking positive actions to
minimize their effects. Most stress management
programs deal with job stress and workplace issues.
Stressor—A stimulus or event that provokes a stress
response in an organism. Stressors can be categorized as acute or chronic, and as external or internal
to the organism.

Selye himself recommended an approach to stress
that he described as ‘‘living wisely in accordance with
natural laws.’’ In his now-classic book The Stress of
Life (1956), he discussed the following as important
dimensions of living wisely:


Benton, Tami D., MD, and Jacqueline Lynch, MSW.
‘‘Adjustment Disorders.’’ eMedicine September 3, 2004.
<http://emedicine.com/med/topic3348.htm>.
Cosen-Binker, L. I., M. G. Binker, G. Negri, and
O. Tiscornia. ‘‘Influence of Stress in Acute Pancreatitis
and Correlation with Stress-Induced Gastric Ulcer.’’
Pancreatology 4 (July 2004): 470–484.
Motzer, S. A., and V. Hertig. ‘‘Stress, Stress Response, and
Health.’’ Nursing Clinics of North America 39 (March
2004): 1–17.
Yates, William R., MD. ‘‘Anxiety Disorders.’’ eMedicine
August 15, 2004. <http://emedicine.com/med/
topic152.htm>.
ORGANIZATIONS

American Institute of Stress. 124 Park Avenue, Yonkers,
NY 10703 (914) 963-1200. Fax: (914) 965-6267.
<http://www.stress.org>.
American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
Canadian Institute of Stress/Hans Selye Foundation.
Medcan Clinic Office, Suite 1500, 150 York Street,
Toronto, Ontario, Canada M5H 3S5. (416) 236-4218.
<http://www.stresscanada.org>.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513. <http://
www.nimh.nih.gov>.
OTHER

‘‘Stress management, General adaptation syndrome,
GAS...’’ <http://www.holisticonline.com/stress/
stress_GAS.htm>.

Adopting an attitude of gratitude toward life rather
than seeking revenge for injuries or slights.



Acting toward others from altruistic rather than selfcentered motives.



Retaining a capacity for wonder and delight in the
genuinely good and beautiful things in life.



Finding a purpose for one’s life and expressing one’s
individuality in fulfilling that purpose.



Keeping a healthy sense of modesty about one’s
goals or achievements.

Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, D.C.: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Psychiatry in Medicine.’’ Section 15, Chapter 1 85
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
GALE ENCYCLOPEDIA OF MEDICINE

Michael V. Zuck, PhD
Rebecca J. Frey, PhD

General anesthetic see Anesthesia, general

General surgery
Definition
General surgery is the treatment of injury, deformity, and disease using operative procedures.

Purpose
General surgery is frequently performed to alleviate
suffering when a cure is unlikely through medication
alone. It can be used for routine procedures performed
in a physician’s office, such as vasectomy, or for more
complicated operations requiring a medical team in a
1587

General surgery

PERIODICALS

KEY TERMS

General surgery

hospital setting, such as laparoscopic cholecystectomy
(removal of the gallbladder). Areas of the body treated
by general surgery include the stomach, liver, intestines,
appendix, breasts, thyroid gland, salivary glands, some
arteries and veins, and the skin. The brain, heart, eyes,
and feet, to name only a few, are areas that require
specialized surgical repair.
New methods and techniques are less invasive than
previous practices, permitting procedures that were considered impossible in the past. For example, microsurgery has been used in reattaching severed body parts by
successfully reconnecting small blood vessels and
nerves.

Precautions
Patients who are obese, smoke, have bleeding
tendencies, or are over 60, need to follow special
precautions, as do patients who have recently experienced an illness such as pneumonia or a heart attack.
Patients on medications such as heart and blood
pressure medicine, blood thinners, muscle relaxants,
tranquilizers, insulin, or sedatives, may require special lab tests prior to surgery and special monitoring
during surgery. Special precautions may be necessary
for patients using mind-altering drugs such as narcotics, psychedelics, hallucinogens, marijuana, sedatives, or cocaine since these drugs may interact with
the anesthetic agents used during surgery.

Description
In earlier times, surgery was a dangerous and dirty
practice. Until the middle of the 19th century, as many
patients died of surgery as were cured. With the discovery and development of general anesthesia in the
mid-1800s, surgery became more humane. And as
knowledge about infections grew, surgery became
more successful as sterile practices were introduced
into the operating room. The last 50 years of the 20th
century have seen continued advancements.
Types of General Surgery
General surgery experienced major advances with
the introduction of the endoscope. This is an instrument for visualizing the interior of a body canal or a
hollow organ. Endoscopic surgery relies on this pencilthin instrument, capable of its own lighting system and
small video camera. The endoscope is inserted through
tiny incisions called portals. While viewing the procedure on a video screen, the surgeon then operates with
various other small, precise instruments inserted
through one or more of the portals. The specific area
1588

of the body treated determines the type of endoscopic
surgery performed. For example, colonoscopy uses an
endoscope, which can be equipped with a device for
obtaining tissue samples for visual examination of the
colon. Gastroscopy uses an endoscope inserted
through the mouth to examine the interior of the
stomach. Arthroscopy refers to joint surgery, and
abdominal procedures are called laparoscopies.
Endoscopy is used in both treatment and diagnosis
especially involving the digestive and female reproductive systems. Endoscopy has advantages over many
other surgical procedures, resulting in a quicker recovery
and shorter hospital stay. This non-invasive technique is
being used for appendectomies, gallbladder surgery,
hysterectomies and the repair of shoulder and knee
ligaments. However, endoscopy does not come without
limitations such as complications and high operating expense. Also, endoscopy doesn’t offer advantages
over conventional surgery in all procedures. Some literature states that as general surgeons become more experienced in their prospective fields, additional non-invasive
surgery will be a more common option to patients.
ONE-DAY SURGERY. One-day surgery is also
termed same-day, or outpatient surgery. Surgical procedures usually take two hours or less and involve
minimal blood loss and a short recovery time. In the
majority of surgical cases, oral medications control
postoperative pain. Cataract removal, laparoscopy,
tonsillectomy, repair of broken bones, hernia repair,
and a wide range of cosmetic procedures are common
same-day surgical procedures. Many individuals prefer the convenience and atmosphere of one-day surgery centers, as there is less competition for attention
with more serious surgical cases. These centers are
accredited by the Joint Commission on Accreditation
of Healthcare Organizations or the Accreditation
Association for Ambulatory Health Care.

Preparation
The preparation of patients has advanced significantly with improved diagnostic techniques and procedures. Before surgery the patient may be asked to
undergo a series of tests including blood and urine
studies, x rays and specific heart studies if the patient’s
past medical history and/or physical exam warrants
this testing. Before any general surgery the physician
will explain the nature of the surgery needed, the reason for the procedure, and the anticipated outcome.
The risks involved will be discussed along with the
types of anesthesia utilized. The expected length of
recovery and limitations imposed during the recovery
period are also explained in detail before any general
surgical procedure.
GALE ENCYCLOPEDIA OF MEDICINE

As part of the preoperative preparation, the
patient will receive printed educational material and
may be asked to review audio or videotapes. The
patient will be instructed to shower or bathe the evening before or morning of surgery and may be asked to
scrub the operative site with a special antibacterial
soap. Instructions will also be given to the patient to
ingest nothing by mouth for a determined period of
time prior to the surgical procedure.

Aftercare
After surgery, blood studies and a laboratory
examination of removed fluid or tissue are often performed especially in the case of cancer surgery. After
the operation, the patient is brought to a recovery
room and vital signs, fluid status, dressings and surgical drains are monitored. Pain medications are offered
and used as necessary. Breathing exercises are encouraged to maximize respiratory function and leg exercises are encouraged to promote adequate circulation
and prevent pooling of blood in the lower extremities.
Patients must have a responsible adult accompany
them home if leaving the same day as the surgery was
performed.

KEY TERMS
Appendectomy—Removal of the appendix.
Endoscope—Instrument for examining visually the
inside of a body canal or a hollow organ such as the
stomach, colon, or bladder.
Hysterectomy—Surgical removal of part or all of
the uterus.
Laparoscopic cholecystectomy—Removal of the
gallbladder using a laparoscope, a fiberoptical
instrument inserted through the abdomen.
Microsurgery—Surgery on small body structures or
cells performed with the aid of a microscope and
other specialized instruments.
Portal—An entrance or a means of entrance.

many times compared to the past. Today’s less invasive surgical procedures have reduced the length of
hospital stays, shortened recovery time, decreased
postoperative pain and decreased the size of surgical
incision. On the average, a conventional abdominal
surgery requires a three to six-day hospital stay and
three to six-week recovery time.

Abnormal results
Abnormal results from general surgery include
persistent pain, swelling, redness, drainage or bleeding
in the surgical area and surgical wound infection
resulting in slow healing.
Resources
ORGANIZATIONS

American Medical Association. 515 N. State St., Chicago, IL
60612. (312) 464-5000. <http://www.ama-assn.org>.

Jeffrey P. Larson, RPT

Risks
One of the risks involved with general surgery is
the potential for postoperative complications. These
complications include—but are not limited to—pneumonia, internal bleeding, and wound infection as well
as adverse reactions to anesthesia.

Generalized anxiety disorder
Definition

Normal results
Advances in diagnostic and surgical techniques
have increased the success rate of general surgery by
GALE ENCYCLOPEDIA OF MEDICINE

Generalized anxiety disorder is a condition characterized by ‘‘free floating’’ anxiety or apprehension
not linked to a specific cause or situation.
1589

Generalized anxiety disorder

Surgical procedures most often require some
type of anesthetic. Some procedures require only
local anesthesia, produced by injecting the anesthetic
agent into the skin near the site of the operation. The
patient remains awake with this form of medication.
Injecting anesthetic agents into a primary nerve
located near the surgical site produces block anesthesia (also known as regional anesthesia), which is a
more extensive local anesthesia. The patient remains
conscious, but is usually sedated. General anesthesia
involves injecting anesthetic agents into the blood
stream and/or inhaling medicines through a mask
placed over the patient’s face. During general
anesthesia, the patient is asleep and an airway tube
is usually placed into the windpipe to help keep the
airway open.

Generalized anxiety disorder

Description
Some degree of fear and anxiety is perfectly normal. In the face of real danger, fear makes people more
alert and also prepares the body to fight or flee (the
so-called ‘‘fight or flight’’ response). When people are
afraid, their hearts beat faster and they breathe faster
in anticipation of the physical activity that will be
required of them. However, sometimes people can
become anxious even when there is no identifiable
cause, and this anxiety can become overwhelming
and very unpleasant, interfering with their daily lives.
People with debilitating anxiety are said to be suffering from anxiety disorders, such as phobias, panic disorders, and generalized anxiety disorder. The person
with generalized anxiety disorder generally has
chronic (officially, having more days with anxiety
than not for at least six months), recurrent episodes
of anxiety that can last days, weeks, or even months.

Causes and symptoms
Generalized anxiety disorder afflicts between
2–3% of the general population, and is slightly more
common in women than in men. It accounts for almost
one-third of cases referred to psychiatrists by general
practitioners.
Generalized anxiety disorder may result from a
combination of causes. Some people are genetically
predisposed to developing it. Psychological traumas
that occur during childhood, such as prolonged
separation from parents, may make people more vulnerable as well. Stressful life events, such as a move, a
major job change, the loss of a loved one, or a divorce,
can trigger or contribute to the anxiety.



difficulty concentrating



irritability



muscle tension



sleep disturbance

While generalized anxiety disorder is not completely debilitating, it can compromise a person’s effectiveness and quality of life.

Diagnosis
Anyone with chronic anxiety for no apparent reason should see a physician. The physician may diagnose the condition based on the patient’s description
of the physical and emotional symptoms. The doctor
will also try to rule out other medical conditions that
may be causing the symptoms, such as excessive caffeine use, thyroid disease, hypoglycemia, cardiac problems, or drug or alcohol withdrawal. Psychological
conditions, such as depressive disorder with anxiety,
will also need to be ruled out.
In June 2004, the Anxiety Disorders Association
of America released follow-up guidelines to help primary care physicians better diagnose and manage
patients with generalized anxiety disorder. They
include considering the disorder when medical causes
for general, vague physical complaints cannot be ruled
out. Since generalized anxiety disorder often co-occurs
with mood disorders and substance abuse, the clinician
may have to treat these conditions as well, and therefore must consider them in making the diagnosis.

Treatment

Psychologically, the person with generalized anxiety disorder may develop a sense of dread for no
apparent reason–the irrational feeling that some
nameless catastrophe is about to happen. Physical
symptoms similar to those found with panic disorder
may be present, although not as severe. They may
include trembling, sweating, heart palpitations (the
feeling of the heart pounding in the chest), nausea,
and ‘‘butterflies in the stomach.’’

Over the short term, a group of tranquilizers called
benzodiazepines, such as clonazepam (Klonipin) may
help ease the symptoms of generalized anxiety disorder.
Sometimes antidepressant drugs, such as amitryptiline
(Elavil), or selective serotonin reuptake inhibitors
(SSRIs), such as paroxetine (Paxil), escitalopram
(Lexapro), and venlafaxine (Effexor), which also has
norepinephrine, may be preferred. Other SSRIs are
fluoxetine (Prozac) and sertraline (Zoloft).

According to the Diagnostic and Statistical Manual
of Mental Disorders, 4th edition, a person must have at
least three of the following symptoms, with some being
present more days than not for at least six months,
in order to be diagnosed with generalized anxiety
disorder:

Psychotherapy can be effective in treating generalized anxiety disorder. The therapy may take many
forms. In some cases, psychodynamically-oriented
psychotherapy can help patients work through this
anxiety and solve problems in their lives. Cognitive
behavioral therapy aims to reshape the way people
perceive and react to potential stressors in their lives.
Relaxation techniques have also been used in treatment, as well as in prevention efforts.



restlessness or feeling on edge



being easily fatigued

1590

GALE ENCYCLOPEDIA OF MEDICINE

Cognitive behavioral therapy—A psychotherapeutic approach that aims at altering cognitions—
including thoughts, beliefs, and images—as a way
of altering behavior.



accurately diagnose a disorder



assess the risk of recurrence in the concerned family
members and their relatives



provide alternatives for decision-making



provide support groups that will help family members cope with the recurrence of a disorder.

Purpose
Prognosis
When properly treated, most patients with generalized anxiety disorder experience improvement in
their symptoms.

Prevention
While preventive measures have not been established, a number of techniques may help manage anxiety, such as relaxation techniques, breathing exercises,
and distraction—putting the anxiety out of one’s mind
by focusing thoughts on something else.
Resources
PERIODICALS

‘‘Guidelines to Assist Primary Care Physicians in Diagnosing
GAD.’’ Psychiatric Times (July 1, 2004): 16.
Sherman, Carl. ‘‘GAD Patients Often Require Combined
Therapy.’’ Clinical Psychiatry News (August 2004): 12–14.
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
Anxiety Disorders Association of America. 11900 Park
Lawn Drive, Ste. 100, Rockville, MD 20852. (800) 5457367. <http://www.adaa.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Robert Scott Dinsmoor
Teresa G. Odle

Genetic counseling
Definition
Genetic counseling aims to facilitate the exchange
of information regarding a person’s genetic legacy. It
attempts to:
GALE ENCYCLOPEDIA OF MEDICINE

Genetic counselors work with people concerned
about the risk of an inherited disease. The counselor
does not prevent the incidence of a disease in a family,
but can help family members assess the risk for certain
hereditary diseases and offer guidance. Many couples
seek genetic counseling because there is a family history of known genetic disorders, infertility, miscarriage, still births, or early infant mortality. Other
reasons for participating in genetic counseling may
be the influences of a job or lifestyle that exposes a
potential parent to health risks such as radiation, chemicals, or drugs. Any family history of mental retardation can be of concern as is a strong family history of
heart disease at an early age. Recent statistics show a
3% chance of delivering a baby with birth defects. An
additional 2% chance of having a baby with Down
syndrome is present for women in their late thirties
and older.
Genetic counseling may take on new emphasis in
the near future as genetic research continues to
advance. In April 2003, the Human Genome Project
announced completion of mapping the entire human
genetic makeup. The project identified more than
1,400 disease genes and completed study of the ethical,
legal, and social issues raised by this expanded knowledge of human genetics. As knowledge expands and
scientists discover more methods to identify and treat
various diseases, people will face more difficult decisions about their own genetic information.

Precautions
Amniocentesis, one of the specific tests used to
gather information for genetic counseling, is best performed between weeks 15 and 17 of a pregnancy and
an additional one to four weeks may be required to
culture skin cells and analyze them. Thus, these test
data are not available to assist prospective parents in
decision-making until the second trimester of the pregnancy. Individuals who participate in genetic counseling and associated testing also must be aware that
there are no cures or treatments for some of the disorders that may be identified.
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KEY TERMS

Genetic counseling

Description
With approximately 2,000 genes identified and
approximately 5,000 disorders caused by genetic
defects, genetic counseling is important in the medical
discipline of obstetrics. Genetic counselors, educated
in the medical and the psychosocial aspects of genetic
diseases, convey complex information to help people
make life decisions. There are limitations to the power
of genetic counseling, though, since many of the diseases that have been shown to have a genetic basis
currently offer no cure (for example, Down syndrome
or Huntington’s disease). Although a genetic counselor cannot predict the future unequivocally, he or she
can discuss the occurrence of a disease in terms of
probability.
Genetic counseling also can help people with diseases they may face in their own lifetimes. A 2003
study in Great Britain found that women with a family
history of breast cancer were less worried about getting
the disease if they had genetic counseling.
A genetic counselor, with the aid of the patient or
family, creates a detailed family pedigree that includes
the incidence of disease in first-degree (parents, siblings, and children) and second-degree (aunts, uncles,
and grandparents) relatives. Before or after this pedigree is completed, certain genetic tests are performed
using DNA analysis, x ray, ultrasound, urine analysis,
skin biopsy, and physical evaluation. For a pregnant
woman, prenatal diagnosis can be made using amniocentesis or chorionic villus sampling.
Family pedigree
An important aspect of the genetic counseling
session is the compilation of a family pedigree or
medical history. To accurately assess the risk of inherited diseases, information on three generations,
including health status and/or cause of death, usually
is needed. If the family history is complicated, information from more distant relatives may be helpful,
and medical records may be requested for any family
members who have had a genetic disorder. Through
an examination of the family history a counselor may
be able to discuss the probability of future occurrence
of genetic disorders. In all cases, the counselor provides information in a non-directive way that leaves
the decision-making up to the client.
Family history questionnaire
As more detailed genetic information becomes
available, physicians and genetic counselors may feel
the need to dig more deeply than a family pedigree
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allows. In 2004, physicians attending an American
College of Medical Genetics meeting announced use
of a structured questionnaire with 50 items to consistent, thorough gather family history data. Although
the questionnaire’s format and terminology were confusing to some patients, once a formula was applied to
the answers, it still helped reviewers agree on a counseling plan 79% of the time.
Screening tests
Screening blood tests help identify individuals
who carry genes for recessive genetic disorders.
Screening tests usually are only done if:


The disease is lethal or causes severe handicaps or
disabilities.



The person is likely to be a carrier due to family
pedigree or membership in an at-risk ethnic, geographic or racial group.



The disorder can be treated or reproductive options
exist.



A reliable test is available.

Genetic disorders such as Tay-Sachs disease,
sickle-cell anemia, and thalassemia meet these criteria,
and screening tests are commonly done to identify
carriers of these diseases. In addition, screening tests
may be done for individuals with family histories of
Huntington’s disease (a degenerative neurological disease) or hemophilia (a bleeding disorder). Such screening tests can eliminate the need for more invasive tests
during a pregnancy.
Another screening test commonly used in the
United States in the alpha-fetoprotein (AFP) test.
This test is done on a sample of maternal blood around
week 16 of a pregnancy. An elevation in the serum
AFP level indicates that the fetus may have certain
birth defects such as neural tube defects (including
spina bifida and anencephaly). If the test yields an
elevated result, it may be run again after seven days.
If the level still is elevated after repeat testing, additional diagnostic tests (e.g. ultrasound and/or amniocentesis) are done in an attempt to identify the specific
birth defect present.
Ultrasound
Ultrasound is a noninvasive procedure that uses
sound waves to produce a reflected image of the fetus
upon a screen. It is used to determine the age and
position of the fetus, and the location of the placenta.
Ultrasound also is useful in detecting visible birth
defects such as spina bifida (a defect in the development of the vertebrae of the spinal column and/or the
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Amniocentesis
Amniocentesis is useful in determining genetic
and developmental disorders not detectable by ultrasound. This procedure involves the insertion of a needle through the abdomen and into the uterus of a
pregnant woman. A sample of amniotic fluid is withdrawn containing skin cells that have been shed by the
fetus. The sample is sent to a laboratory where fetal
cells contained in the fluid are isolated and grown in
order to provide enough genetic material for testing.
This takes about seven to 14 days. The material then is
extracted and treated so that visual examination for
defects can be made. For some disorders, like TaySachs disease, the simple presence of a telltale chemical compound in the amniotic fluid is enough to confirm a diagnosis.
While it has been routine in recent years to suggest
amniocentesis to every pregnant woman age 35 and
older to screen for Down syndrome, evidence in 2003
began suggesting that it made more sense and was
safer to offer blood test screening. The ‘‘triple screen’’
blood test can identify about three-fourths of Down
syndrome cases by measuring certain chemicals in the
mother’s blood.
Chorionic villus sampling
Chorionic villus sampling involves the removal of
a small amount of tissue directly from the chorionic
villi (minute vascular projections of the fetal chorion
that combine with maternal uterine tissue to form the
placenta). In the laboratory, the chromosomes of the
fetal cells are analyzed for number and type. Extra
chromosomes, such as are present in Down syndrome,
can be identified. Additional laboratory tests can be
performed to look for specific disorders and the results
usually are available within a week after the sample is
taken. The primary benefit of this procedure is that it
is usually performed between weeks 10 and 12 of a
pregnancy, allowing earlier detection of fetal disorders. A 2003 study reported that this test resulted in
fewer cases of pregnancy loss, amniotic fluid leakage,
or birth defects than early amniocentesis.

Preparation
Genetic diagnosis requires that a couple share information about inherited disorders in their background
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with the genetic counselor, including details of any
genetic diseases in either family. A couple undergoing
genetic counseling also reports any past miscarriages
and discusses the possibility of exposure to chemicals,
radiation (including x rays), or other occupational environmental hazards. The couple also needs to disclose
information about personal habits before or during
pregnancy such as drug or alcohol abuse and the use of
prescription or over-the-counter drugs taken by the
mother since the beginning of pregnancy. The genetic
counselor explains the procedures used in testing that
will be done and describes what each test can and cannot
reveal.

Aftercare
Genetic counseling provides couples with information that can help them make decisions about
future pregnancies. It also gives couples additional
time to emotionally prepare if a disorder is detected
in the fetus. The counselor discusses the results of
testing and informs the couple if a problem is apparent. The doctor or genetic counselor also discusses the
treatment options available. Genetic counseling is
done in a non-directive way, so that any treatment
selected remains the personal choice of the individuals
involved. Genetic counseling can provide information
essential for family planning and pregnancy management, thus maximizing the chances of a positive
outcome.

Risks
Because prenatal testing, such as amniocentesis
and chorionic villus sampling, is invasive and carries
a 1% risk of miscarriage it should never be considered
routine.

Normal results
Screening tests and/or prenatal tests reveal no
birth defects or genetic abnormalities.

Abnormal results
A birth defect or genetic disorder is detected. The
early diagnosis of birth defects and genetic disorders
allows a greater number of treatment options. Some
disorders can be treated in utero (before birth while
the fetus is still in the uterus), while others may require
early delivery, immediate surgery, or cesarean section
to minimize fetal trauma. Prior warning of fetal difficulties allows parents time to prepare emotionally for
the birth of the child. In some instances, termination
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spinal cord). It also is useful for detecting heart
defects, and malformations of the head, face, body,
and limbs. This procedure, however, cannot detect
biochemical or chromosomal alterations in the fetus.

Genetic testing

KEY TERMS
Sickle-cell anemia—A chronic, inherited blood disorder characterized by crescent-shaped red blood
cells. It occurs primarily in people of African descent, and produces symptoms including episodic
pain in the joints, fever, leg ulcers, and jaundice.
Tay-Sachs disease—A hereditary disease affecting
young children of eastern European Jewish descent. This disease is caused by an enzyme deficiency leading to the accumulation of gangliosides
(galactose-containing cerebrosides) found in the
surface membranes of nerve cells in the brain
and nerve tissue. This deficiency results in mental
retardation, convulsions, blindness, and, finally,
death.
Thalassemia—An inherited group of anemias occurring primarily among people of Mediterranean descent. It is caused by defective formation of part of the
hemoglobin molecule.

of the pregnancy may be chosen. Whatever the test
results, this information is essential for family planning and pregnancy management.
Resources
PERIODICALS

‘‘Best Early Test.’’ Fit Pregnancy (October-November,
2003): 37.
‘‘Blood Test Screening Reduces Need for Amniocentesis.’’
Womenós Health Weekly (December 4, 2003): 51.
Bodenhorn, Nancy, and Gerald Lawson. ‘‘Genetic
Counseling: Implications for Community Counselors.’’
Journal of Counseling and Development (Fall 2003):
497–495.
‘‘Genetic Counseling Questionnaire Helps Assess FamilyÆs
Genetic History.’’ Internal Medicine News (April 15,
2004): 45.
‘‘Genetic Counseling Reduces WomenÆs Fears.’’ Womenós
Health Weekly (September 11, 2003): 23.
Wechsler, Jill. ‘‘From Genome Exploration to Drug
Development.’’ Pharmaceutical Technology Europe
(June 2003): 18–23.
ORGANIZATIONS

American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://www.amaassn.org>.
American Society of Human Genetics. 9650 Rockville
Pike, Bethesda, MD 20814-3998. (301) 571-1825.
<http://www.faseb.org/genetics/ashg/
ashgmenu.htm>.
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March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914) 4287100. resourcecenter@modimes.org. <http://
www.modimes.org>.

Jeffrey P. Larson, RPT
Teresa G. Odle

Genetic studies see Genetic testing

Genetic testing
Definition
A genetic test examines the genetic information
contained inside a person’s cells, called DNA, to determine if that person has or will develop a certain disease
or could pass a disease to his or her offspring. Genetic
tests also determine whether or not couples are at a
higher risk than the general population for having a
child affected with a genetic disorder.

Purpose
Some families or ethnic groups have a higher incidence of a certain disease than the population as a
whole. For example, individuals from Eastern
European, Ashkenazi Jewish descent are at higher
risk for carrying genes for rare conditions that occur
much less frequently in populations from other parts
of the world. Before having a child, a couple from such
a family or ethnic group may want to know if their
child would be at risk of having that disease. Genetic
testing for this type of purpose is called genetic
screening.
During pregnancy, a baby’s cells can be studied for
certain genetic disorders or chromosomal problems
such as Down syndrome. Chromosome testing is most
commonly offered when the mother is 35 years or
older at the time of delivery. When there is a family
medical history of a genetic disease or there are individuals in a family affected with developmental and
physical delays, genetic testing also may be offered
during pregnancy. Genetic testing during pregnancy
is called prenatal diagnosis.
Prior to becoming pregnant, couples who are having difficulty conceiving a child or who have suffered
multiple miscarriages may be tested to see if a genetic
cause can be identified.
A genetic disease may be diagnosed at birth by
doing a physical evaluation of the baby and observing
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positive, will help prepare the person undergoing testing. During the genetic counseling session, the individual interested in genetic testing will be asked to
consider how the test results will affect his or her life,
family, and future decisions.

There are several genetic diseases and conditions
in which the symptoms do not occur until adulthood.
One such example is Huntington’s disease. This is a
serious disorder affecting the way in which individuals
walk, talk and function on a daily basis. Genetic testing may be able to determine if someone at risk will in
fact develop the disease.

After this discussion, the person should have the
opportunity to indicate in writing that he or she gave
informed consent to have the test performed, verifying
that the counselor provided complete and understandable information.

Genetic testing may take on new emphasis in the
near future as genetic research continues to advance.
In April 2003, the Human Genome Project announced
completion of mapping the entire human genetic
makeup. The project identified more than 1,400 disease genes and completed study of the ethical, legal,
and social issues raised by this expanded knowledge of
human genetics. As knowledge expands and scientists
discover more methods to identify and treat various
diseases, people will face more difficult decisions
about their own genetic information. In fact, the
amount of genetic testing was increasing internationally in 2003, especially for rare diseases.
Some genetic defects may make a person more
susceptible to certain types of cancer. Testing for
these defects can help predict a person’s risk. Other
types of genetic tests help diagnose and predict and
monitor the course of certain kinds of cancer, particularly leukemia and lymphoma.

Precautions
Because genetic testing is not always accurate and
because there are many concerns surrounding insurance and employment discrimination for the individual receiving a genetic test, genetic counseling should
always be performed prior to genetic testing. A genetic
counselor is an individual with a master’s degree in
genetic counseling. A medical geneticist is a physician
specializing and board certified in genetics.
A genetic counselor reviews the person’s family
history and medical records and the reason for the test.
The counselor explains the likelihood that the test will
detect all possible causes of the disease in question
(known as the sensitivity of the test), and the likelihood that the disease will develop if the test is positive (known as the positive predictive value of the test).
Learning about the disease in question, the benefits and risks of both a positive and a negative result,
and what treatment choices are available if the result is
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Description
Genes and chromosomes
Deoxyribonucleic acid (DNA) is a long molecule
made up of two strands of genetic material coiled
around each other in a unique double helix structure.
This structure was discovered in 1953 by Francis Crick
and James Watson.
DNA is found in the nucleus, or center, of most
cells (Some cells, such as a red blood cell, don’t have a
nucleus). Each person’s DNA is a unique blueprint,
giving instructions for a person’s physical traits, such
as eye color, hair texture, height, and susceptibility to
disease. DNA is organized into structures called
chromosomes.
The instructions are contained in DNA’s long
strands as a code spelled out by pairs of bases, which
are four chemicals that make up DNA. The bases occur
as pairs because a base on one strand lines up with and
is bound to a corresponding base on the other strand.
The order of these bases form DNA’s code. The order
of the bases on a DNA strand is important to ensuring
that we are not affected with any genetic diseases. When
the bases are out of order, or missing, our cells often do
not produce important proteins which can lead to a
genetic disorder. While our genes are found in every
cell of our body, not every gene is functioning all of the
time. Some genes are turned on during critical points in
development and then remain silent for the rest of our
lives. Other genes remain active all of our lives so that
our cells can produce important proteins that help us
digest food properly or fight off the common cold.
The specific order of the base pairs on a strand of
DNA is important in order for the correct protein to
be produced. A grouping of three base pairs on the
DNA strand is called a codon. Each codon, or three
base pairs, comes together to spell a word. A string of
many codons together can be thought of as a series of
words all coming together to make a sentence. This
sentence is what instructs our cells to make a protein
that helps our bodies function properly.
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characteristics of the disorder. Genetic testing can help
to confirm the diagnosis made by the physical evaluation. In addition, genetic testing is used routinely on all
newborns to screen for certain genetic diseases that
can affect a newborn baby’s health shortly after birth.

Genetic testing

Our DNA strands, containing a hundred to several thousand copies of genes, are found on structures
called chromosomes. Each cell typically has 46
chromosomes arranged into 23 pairs. Each parent
contributes one chromosome to each pair. The first
22 pairs are called autosomal chromosomes, or nonsex chromosomes, and are assigned a number from 1–
22. The last pair are the sex chromosomes and include
the X and Y chromosomes. If a child receives an
X chromosome from each parent, the child is female.
If a child receives an X from the mother, and a Y from
the father, the child is male.
Just as each parent contributes one chromosome to
each pair, so each parent contributes one gene from each
chromosome. The pair of genes produces a specific trait
in the child. In autosomal dominant conditions, it takes
only one copy of a gene to influence a specific trait. The
stronger gene is called dominant; the weaker gene, recessive. Two copies of a recessive gene are needed to control a trait while only one copy of a dominant gene is
needed. Our sex chromosomes, the X and the Y, also
contain important genes. Some genetic diseases are
caused by missing or altered genes on one of the sex
chromosomes. Males are most often affected by sex
chromosome diseases when they inherit an X chromosome with missing or mutated genes from their mother.
TYPES OF GENETIC MUTATIONS. Genetic disease
results from a change, or mutation, in a chromosome
or in one or several base pairs on a gene. Some of us
inherit these mutations from our parents, called hereditary or germline mutations, while other mutations
can occur spontaneously, or for the first time in an
affected child. For many of the adult on-set diseases,
genetic mutations can occur over the lifetime of the
individual. This is called acquired or somatic mutations and these occur while the cells are making copies
of themselves or dividing in two. There may be some
environmental effects, such as radiation or other chemicals, which can contribute to these types of mutations as well.

There are a variety of different types of mutations
that can occur in our genetic code to cause a disease.
And for each genetic disease, there may be more than
one type of mutation to cause the disease. For some
genetic diseases, the same mutation occurs in every
individual affected with the disease. For example, the
most common form of dwarfism, called achondroplasia, occurs because of a single base pair substitution.
This same mutation occurs in all individuals affected
with the disease. Other genetic diseases are caused by
different types of genetic mutations that may occur
anywhere along the length of a gene. For example,
cystic fibrosis, the most common genetic disease in
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the caucasian population is caused by over hundreds
of different mutations along the gene. Individual
families may carry the same mutation as each other,
but not as the rest of the population affected with the
same genetic disease.
Some genetic diseases occur as a result of a larger
mutation which can occur when the chromosome itself
is either rearranged or altered or when a baby is born
with more than the expected number of chromosomes.
There are only a few types of chromosome rearrangements which are possibly hereditary, or passed on from
the mother or the father. The majority of chromosome
alterations where the baby is born with too many chromosomes or missing a chromosome, occur sporadically
or for the first time with a new baby.
The type of mutation that causes a genetic disease
will determine the type of genetic test to be performed.
In some situations, more than one type of genetic test
will be performed to arrive at a diagnosis. The cost of
genetic tests vary: chromosome studies can cost hundreds of dollars and certain gene studies, thousands.
Insurance coverage also varies with the company and
the policy. It may take several days or several weeks to
complete a test. Research testing where the exact location of a gene has not yet been identified, can take
several months to years for results.

Types of Genetic Testing
Direct DNA mutation analysis
Direct DNA sequencing examines the direct base
pair sequence of a gene for specific gene mutations.
Some genes contain more than 100,000 bases and a
mutation of any one base can make the gene nonfunctional and cause disease. The more mutations possible,
the less likely it is for a test to detect all of them. This
test usually is done on white blood cells from a person’s
blood but also can be performed on other tissues. There
are different ways in which to perform direct DNA
mutation analysis. When the specific genetic mutation
is known, it is possible to perform a complete analysis of
the genetic code, also called direct sequencing. There are
several different lab techniques used to test for a direct
mutation. One common approach begins by using chemicals to separate DNA from the rest of the cell. Next,
the two strands of DNA are separated by heating.
Special enzymes (called restriction enzymes) are added
to the single strands of DNA and then act like scissors,
cutting the strands in specific places. The DNA fragments are then sorted by size through a process called
electrophoresis. A special piece of DNA, called a probe,
is added to the fragments. The probe is designed to bind
to specific mutated portions of the gene. When bound to
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Indirect DNA Testing
Family linkage studies are done to study a disease
when the exact type and location of the genetic alteration is not known, but the general location on the
chromosome has been identified. These studies are
possible when a chromosome marker has been found
associated with a disease. Chromosomes contain certain regions that vary in appearance between individuals. These regions are called polymorphisms and do
not cause a genetic disease to occur. If a polymorphism is always present in family members with the same
genetic disease, and absent in family members without
the disease, it is likely that the gene responsible for the
disease is near that polymorphism. The gene mutation
can be indirectly detected in family members by looking for the polymorphism.

A karyotype is the final step in the chromosome
analysis. After the chromosomes are counted, a photograph is taken of the chromosomes from one or more
cells as seen through the microscope. Then the
chromosomes are cut out and arranged side-by-side
with their partner in ascending numerical order, from
largest to smallest. The karyotype is done either manually or using a computer attached to the microscope.
Chromosome analysis also is called cytogenetics.

Applications for Genetic Testing
Newborn screening
Genetic testing is used most often for newborn
screening. Every year, millions of newborn babies
have their blood samples tested for potentially serious
genetic diseases.
Carrier testing

To look for the polymorphism, DNA is isolated
from cells in the same way it is for direct DNA mutation analysis. A probe is added that will detect the
large polymorphism on the chromosome. When
bound to the probe, this region will appear on x-ray
film with a distinct banding pattern. The pattern of
banding of a person being tested for the disease is
compared to the pattern from a family member
affected by the disease.

An individual who has a gene associated with a
disease but never exhibits any symptoms of the disease
is called a carrier. A carrier is a person who is not
affected by the mutated gene he or she possesses, but
can pass the gene to an offspring. Genetic tests have
been developed that tell prospective parents whether
or not they are carriers of certain diseases. If one or
both parents are a carrier, the risk of passing the
disease to a child can be predicted.

Linkage studies have disadvantages not found in
direct DNA mutation analysis. These studies require
multiple family members to participate in the testing.
If key family members choose not to participate, the
incomplete family history may make testing other
members useless. The indirect method of detecting a
mutated gene also causes more opportunity for error.

To predict the risk, it is necessary to know if the
gene in question is autosomal or sex-linked. If the gene
is carried on any one of chromosomes 1–22, the resulting disease is called an autosomal disease. If the gene is
carried on the X or Y chromosome, it is called a sexlinked disease.

Chromosome analysis
Various genetic syndromes are caused by structural chromosome abnormalities. To analyze a person’s chromosomes, his or her cells are allowed to
grow and multiply in the laboratory until they reach
a certain stage of growth. The length of growing time
varies with the type of cells. Cells from blood and bone
marrow take one to two days; fetal cells from amniotic
fluid take seven to 10 days.
When the cells are ready, they are placed on a
microscope slide using a technique to make them
burst open, spreading their chromosomes. The slides
are stained: the stain creates a banding pattern unique
to each chromosome. Under a microscope, the
chromosomes are counted, identified, and analyzed
based on their size, shape, and stained appearance.
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Sex-linked diseases, such as the bleeding condition
hemophilia, are usually carried on the X chromosome.
A woman who carries a disease-associated mutated
gene on one of her X chromosomes, has a 50% chance
of passing the gene to her son. A son who inherits that
gene will develop the disease because he does not
have another normal copy of the gene on a second
X chromosome to compensate for the mutated copy.
A daughter who inherits the disease associated
mutated gene from her mother on one of her X chromosomes will be at risk for having a son affected with
the disease.
The risk of passing an autosomal disease to a child
depends on whether the gene is dominant or recessive.
A prospective parent carrying a dominant gene has a
50% chance of passing the gene to a child. A child
needs to receive only one copy of the mutated gene to
be affected by the disease.
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the probe, the mutated portions appear on x-ray film
with a distinct banding pattern.

Genetic testing

of two and five. This disease was previously detected
by looking for a missing enzyme. The mutated gene
has now been identified and can be detected using
direct DNA mutation analysis.
Presymptomatic testing
Not all genetic diseases show their effect immediately at birth or early in childhood. Although the gene
mutation is present at birth, some diseases do not
appear until adulthood. If a specific mutated gene
responsible for a late-onset disease has been identified,
a person from an affected family can be tested before
symptoms appear.
A scientist examines a DNA sequencing autoradiogram on a
light box. (Photo Researchers, Inc. Reproduced by permission.)

If the gene is recessive, a child needs to receive two
copies of the mutated gene, one from each parent, to be
affected by the disease. When both prospective parents
are carriers, their child has a 25% chance of inheriting
two copies of the mutated gene and being affected by
the disease; a 50% chance of inheriting one copy of the
mutated gene, and being a carrier of the disease but not
affected; and a 25% chance of inheriting two normal
genes. When only one prospective parent is a carrier, a
child has a 50% chance of inheriting one mutated gene
and being an unaffected carrier of the disease, and a
50% chance of inheriting two normal genes.

Huntington’s disease is one example of a lateonset autosomal dominant disease. Its symptoms
of mental confusion and abnormal body movements
do not appear until middle to late adulthood. The
chromosome location of the gene responsible for
Huntington’s chorea was located in 1983 after studying the DNA from a large Venezuelan family affected
by the disease. Ten years later the gene was identified.
A test now is available to detect the presence of the
expanded base pair sequence responsible for causing
the disease. The presence of this expanded sequence
means the person will develop the disease.

Cystic fibrosis is a disease that affects the lungs
and pancreas and is discovered in early childhood. It is
the most common autosomal recessive genetic disease
found in the caucasian population: one in 25 people of
Northern European ancestry are carriers of a mutated
cystic fibrosis gene. The gene, located on chromosome
7, was identified in 1989.

The specific genetic cause of Alzheimer’s disease,
another late onset disease, is not as clear. Although
many cases appear to be inherited in an autosomal
dominant pattern, many other cases exist as single
incidents in a family. Like Huntington’s, symptoms
of mental deterioration first appear in adulthood.
Genetic research has found an association between
this disease and genes on four different chromosomes.
The validity of looking for these genes in a person
without symptoms or without family history of the
disease is still being studied.

The gene mutation for cystic fibrosis is detected by
a direct DNA test. More than 600 mutations of the
cystic fibrosis gene have been found; each of these
mutations causes the same disease. Tests are available
for the most common mutations. Tests that check for
86 of the most common mutations in the Caucasian
population will detect 90% of carriers for cystic fibrosis. (The percentage of mutations detected varies
according to the individual’s ethnic background). If a
person tests negative, it is likely, but not guaranteed
that he or she does not have the gene. Both prospective
parents must be carriers of the gene to have a child
with cystic fibrosis.

CANCER SUSCEPTIBILITY TESTING. Cancer can
result from an inherited (germline) mutated gene or a
gene that mutated sometime during a person’s lifetime
(acquired mutation). Some genes, called tumor suppressor genes, produce proteins that protect the body
from cancer. If one of these genes develops a mutation,
it is unable to produce the protective protein. If the
second copy of the gene is normal, its action may be
sufficient to continue production, but if that gene later
also develops a mutation, the person is vulnerable to
cancer. Other genes, called oncogenes, are involved in
the normal growth of cells. A mutation in an oncogene
can cause too much growth, the beginning of cancer.

Tay-Sachs disease, also autosomal recessive,
affects children primarily of Ashkenazi Jewish descent. Children with this disease die between the ages

Direct DNA tests currently are available to look
for gene mutations identified and linked to several
kinds of cancer. People with a family history of these

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GALE ENCYCLOPEDIA OF MEDICINE

Cancer susceptibility tests are most useful when a
positive test result can be followed with clear treatment options. In families with familial polyposis of the
colon, testing a child for a mutated APC gene can
reveal whether or not the child needs frequent monitoring for the disease. In 2003, reports showed that
genetic testing for high-risk colon cancer patients has
improved risk assessment. In families with potentially
fatal familial medullary thyroid cancer or multiple
endocrine neoplasia type 2, finding a mutated RET
gene in a child provides the opportunity for that child
to have preventive removal of the thyroid gland. In the
same way, MSH1 and MSH2 mutations can reveal
which members in an affected family are vulnerable
to familiar colorectal cancer and would benefit from
aggressive monitoring.
In 1994, a mutation linked to early-onset familial
breast and ovarian cancer was identified. BRCA1 is
located on chromosome 17. Women with a mutated
form of this gene have an increased risk of developing
breast and ovarian cancer. A second related gene,
BRCA2, was later discovered. Located on chromosome 13, it also carries increased risk of breast and
ovarian cancer. Although both genes are rare in the
general population, they are slightly more common in
women of Ashkenazi Jewish descent.
When a woman is found to have a mutation of one
of these genes, the likelihood that she will get breast or
ovarian cancer increases, but not to 100%. Other genetic
and environmental factors influence the outcome.
Testing for these genes is most valuable in families
where a mutation has already been found. BRCA1
and BRCA2 are large genes; BRCA1 includes
100,000 bases. More than 120 mutations to this gene
have been discovered, but a mutation could occur in
any one of the bases. Studies show tests for these genes
may miss 30% of existing mutations. The rate of
missed mutations, the unknown disease likelihood in
spite of a positive result, and the lack of a clear preventive response to a positive result, make the value of
this test for the general population uncertain.

time of delivery, experienced multiple miscarriages, or
reports a family history of a genetic abnormality.
Prenatal testing is done on the fetal cells from a chorionic villus sampling (from the baby’s developing placenta) at 9–12 weeks or from the amniotic fluid (the
fluid surrounding the baby) at 15–22 weeks of pregnancy. Cells from amniotic fluid grow for seven to
10 days before they are ready to be analyzed.
Chorionic villi cells have the potential to grow faster
and can be analyzed sooner.
Chromosome analysis using blood cells is done on
a child who is born with or later develops signs of
mental retardation or physical malformation. In the
older child, chromosome analysis may be done to
investigate developmental delays.
Extra or missing chromosomes cause mental and
physical abnormalities. A child born with an extra
chromosome 21 (trisomy 21) has Down syndrome.
An extra chromosome 13 or 18 also produce well
known syndromes. A missing X chromosome causes
Turner syndrome and an extra X in a male causes
Klinefelter syndrome. Other abnormalities are caused
by extra or missing pieces of chromosomes. Fragile
X syndrome is a sex-linked disease, causing mental
retardation in males.
Chromosome material also may be rearranged,
such as the end of chromosome 1 moved to the end
of chromosome 3. This is called a chromosomal translocation. If no material is added or deleted in the
exchange, the person may not be affected. Such an
exchange, however, can cause infertility or abnormalities if passed to children.
Evaluation of a man and woman’s infertility
or repeated miscarriages will include blood studies of
both to check for a chromosome translocation. Many
chromosome abnormalities are incompatible with life;
babies with these abnormalities often miscarrry during
the first trimester. Cells from a baby that died before
birth can be studied to look for chromosome abnormalities that may have caused the death.
Cancer diagnosis and prognosis

Prenatal and postnatal chromosome analysis

Certain cancers, particularly leukemia and lymphoma, are associated with changes in chromosomes:
extra or missing complete chromosomes, extra or
missing portions of chromosomes, or exchanges of
material (translocations) between chromosomes.
Studies show that the locations of the chromosome
breaks are at locations of tumor suppressor genes or
oncogenes.

Chromosome analysis can be done on fetal cells
primarily when the mother is age 35 or older at the

Chromosome analysis on cells from blood, bone
marrow, or solid tumor helps diagnose certain kinds of

GALE ENCYCLOPEDIA OF MEDICINE

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Genetic testing

cancers are those most likely to be tested. If one of
these mutated genes is found, the person is more susceptible to developing the cancer. The likelihood that
the person will develop the cancer, even with the
mutated gene, is not always known because other
genetic and environmental factors also are involved
in the development of cancer.

Genetic testing

leukemia and lymphoma and often helps predict how
well the person will respond to treatment. After treatment has begun, periodic monitoring of these chromosome changes in the blood and bone marrow gives the
physician information as to the effectiveness of the
treatment.
A well-known chromosome rearrangement is
found in chronic myelogenous leukemia. This leukemia
is associated with an exchange of material between
chromosomes 9 and 22. The resulting smaller chromosome 22 is called the Philadelphia chromosome.

Preparation
Most tests for genetic diseases of children and
adults are done on blood. To collect the 5–10 mL of
blood needed, a healthcare worker draws blood from a
vein in the inner elbow region. Collection of the sample takes only a few minutes.
Prenatal testing is done either on amniotic fluid or
a chorionic villus sampling. To collect amniotic fluid,
a physician performs a procedure called amniocentesis.
An ultrasound is done to find the baby’s position and
an area filled with amniotic fluid. The physician inserts
a needle through the woman’s skin and the wall of her
uterus and withdraws 5–10 mL of amniotic fluid.
Placental tissue for a chorionic villus sampling is
taken through the cervix. Each procedure takes
approximately 30 minutes. A 2003 study comparing
the two tests reported that chorionic villus sampling
resulted in fewer cases of pregnancy loss, amniotic
fluid leakage, and birth defects.
Bone marrow is used for chromosome analysis in
a person with leukemia or lymphoma. The person is
given local anesthesia. Then the physician inserts a
needle through the skin and into the bone (usually
the sternum or hip bone). One-half to 2 mL of bone
marrow is withdrawn. This procedure takes approximately 30 minutes.

Aftercare
After blood collection the person can feel discomfort or bruising at the puncture site or may become
dizzy or faint. Pressure to the puncture site until the
bleeding stops reduces bruising. Warm packs to the
puncture site relieve discomfort.
Chorionic villus sampling, amniocentesis and
bone marrow procedures are done under a physician’s
supervision. The person is asked to rest after the
procedure and is watched for weakness and signs of
bleeding.
1600

Risks
Collection of amniotic fluid and chorionic villus
sampling, have the risk of miscarriage, infection, and
bleeding; the risks are higher for the chorionic villus
sampling. Because of the potential risks for miscarriage,
0.5% following the amniocentesis and 1% following the
chorionic villus sampling procedure, both of these prenatal tests are offered to couples, but not required. A
woman should tell her physician immediately if she has
cramping, bleeding, fluid loss, an increased temperature, or a change in the baby’s movement following
either of these procedures.
After bone marrow collection, the puncture site
may become tender and the person’s temperature may
rise. These are signs of a possible infection.
Genetic testing involves other nonphysical risks.
Many people fear the possible loss of privacy about
personal health information. Results of genetic tests
may be reported to insurance companies and affect
a person’s insurability. Some people pay out-ofpocket for genetic tests to avoid this possibility.
Laws have been proposed to deal with this problem.
Other family members may be affected by the results
of a person’s genetic test. Privacy of the person
tested and the family members affected is a consideration when deciding to have a test and to share the
results.
A positive result carries a psychological burden,
especially if the test indicates the person will develop a
disease, such as Huntington’s chorea. The news that a
person may be susceptible to a specific kind of cancer,
while it may encourage positive preventive measures,
also may negatively shadow many decisions and
activities.
A genetic test result may also be inconclusive,
meaning no definitive result can be given to the individual or family. This may cause the individual to feel
more anxious and frustrated and experience psychological difficulties.
Prior to undergoing genetic testing, individuals
need to learn from the genetic counselor the likelihood
that the test could miss a mutation or abnormality.

Normal results
A normal result for chromosome analysis is
46, XX or 46, XY. This means there are 46 chromosomes (including two X chromosomes for a female or
one X and one Y for a male) with no structural
abnormalities. A normal result for a direct DNA
mutation analysis or linkage study is no gene mutation
found.
GALE ENCYCLOPEDIA OF MEDICINE

Autosomal disease—A disease caused by a gene
located on a chromosome other than a sex chromosome (autosomal chromosome).
Carrier—A person who possesses a gene for an abnormal trait without showing signs of the disorder. The
person may pass the abnormal gene on to offspring.

sequence found on a section of DNA. Each gene is
found on a precise location on a chromosome.
Karyotype—A standard arrangement of photographic or computer-generated images of chromosome pairs from a cell in ascending numerical
order, from largest to smallest.

Chromosome—A microscopic thread-like structure
found within each cell of the body that consists of a
complex of proteins and DNA. Humans have 46
chromosomes arranged into 23 pairs. Changes in
either the total number of chromosomes or their
shape and size (structure) may lead to physical or
mental abnormalities.
Deoxyribonucleic acid (DNA)—The genetic material in cells that holds the inherited instructions for
growth, development, and cellular functioning.

Mutation—A permanent change in the genetic
material that may alter a trait or characteristic of
an individual, or manifest as disease, and can be
transmitted to offspring.
Positive predictive value (PPV)—The probability
that a person with a positive test result has, or will
get, the disease.
Recessive gene—A type of gene that is not expressed
as a trait unless inherited by both parents.

Dominant gene—A gene, whose presence as a single copy, controls the expression of a trait.
Enzyme—A protein that catalyzes a biochemical
reaction or change without changing its own structure or function.

Sensitivity—The proportion of people with a disease who are correctly diagnosed (test positive
based on diagnostic criteria). The higher the sensitivity of a test or diagnostic criteria, the lower the
rate of ‘false negatives,’ people who have a disease
but are not identified through the test.

Gene—A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular

Sex-linked disorder—A disorder caused by a gene
located on a sex chromosome, usually the X
chromosome.

There can be some benefits from genetic testing when
the individual tested is not found to carry a genetic
mutation. Those who learn with certainty they are no
longer at risk for a genetic disease may choose not to
undergo preventive therapies and may feel less anxious
and relieved.

counselor to fully understand the meaning of the
results, learn what options are available based on the
test result, and the risks and benefits of each of those
options.
Resources
PERIODICALS

Abnormal results
An abnormal chromosome analysis report will
include the total number of chromosomes and will
identify the abnormality found. Tests for gene mutations will report the mutations found.
There are many ethical issues to consider with an
abnormal prenatal test result. Many of the diseases
tested for during a pregnancy cannot be treated or
cured. In addition, some diseases tested for during
pregnancy may have a late-onset of symptoms or
have minimal effects on the affected individual.
Before making decisions based on an abnormal
test result, the person should meet again with a genetic
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Best Early Test.’’ Fit Pregnancy (October-November,
2003): 37.
Bodenhorn, Nancy, and Gerald Lawson. ‘‘Genetic
Counseling: Implications for Community Counselors.’’
Journal of Counseling and Development (Fall 2003):
497–495.
‘‘Genetic Testing for High-risk Colon Cancer Patients has
Improved Risk Assessment.’’ Genomics & Genetics
Weekly (August 1, 2003): 18.
‘‘Genetic Testing Increasing Internationally.’’ Health &
Medicine Week (September 29, 2003): 283.
Wechsler, Jill. ‘‘From Genome Exploration to Drug
Development.’’ Pharmaceutical Technology Europe
(June 2003): 18–23.
Yan, Hai. ‘‘Genetic Testing-Present and Future.’’ Science
(September 15, 2000): 1890-1892.
1601

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KEY TERMS

Genital herpes

Description

ORGANIZATIONS

Alliance of Genetic Support Groups. 4301 Connecticut Ave.
NW, Suite 404, Washington, DC 20008. (202) 966-5557.
Fax: (202) 966-8553. <http://
www.geneticalliance.org>.
American College of Medical Genetics. 9650 Rockville
Pike, Bethesda, MD 20814-3998. (301) 571-1825.
<http://www.faseb.org/genetics/acmg/
acmgmenu.htm>.
American Society of Human Genetics. 9650 Rockville Pike,
Bethesda, MD 20814-3998. (301) 571-1825. <http://
www.faseb.org/genetics/ashg/ashgmenu.htm>.
Centers for Disease Control. GDP Office, 4770 Buford
Highway NE, Atlanta, GA 30341-3724. (770) 488-3235.
<http://www.cdc.gov/genetics>.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (888) 6634637. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Human Genome Research Institute. The National
Institutes of Health, 9000 Rockville Pike, Bethesda,
MD 20892. (301) 496-2433. <http://
www.nhgri.nih.gov>.
National Society of Genetic Counselors. 233 Canterbury
Dr., Wallingford, PA 19086-6617. (610) 872-1192.
<http://www.nsgc.org/GeneticCounselingYou.asp>.
OTHER

Blazing a Genetic Trail. Online genetic tutorial. <http://
www.hhmi.org/GeneticTrail/>.
The Gene Letter. Online newsletter. <http://
www.geneletter.org>.
Online Mendelian Inheritance in Man. Online genetic testing
information sponsored by National Center for
Biotechnology Information. <http://www.ncbi.nlm.nih.gov/Omim/>.
Understanding Gene Testing. Online brochure produced by
the U.S. Department of Health and Human Services.
<http://www.gene.com/ae/AE/AEPC/NIH/
index.html>.

Katherine S. Hunt, MS
Teresa G. Odle

Genital herpes
Definition
Genital herpes is a sexually transmitted disease
caused by a herpes virus. The disease is characterized
by the formation of fluid-filled, painful blisters in the
genital area.
1602

Genital herpes (herpes genitalis, herpes progenitalis) is characterized by the formation of fluid-filled
blisters on the genital organs of men and women.
The word ‘‘herpes’’ comes from the Greek adjective
herpestes, meaning creeping, which refers to the serpent-like pattern that the blisters may form. Genital
herpes is a sexually transmitted disease which means
that it is spread from person-to-person only by sexual
contact. Herpes may be spread by vaginal, anal, and
oral sexual activity. It is not spread by objects (such as
a toilet seat or doorknob), swimming pools, hot tubs,
or through the air.
Genital herpes is a disease resulting from an infection by a herpes simplex virus. There are eight different kinds of human herpes viruses. Only two of these,
herpes simplex types 1 and 2, can cause genital herpes.
It has been commonly believed that herpes simplex
virus type 1 infects above the waist (causing cold
sores) and herpes simplex virus type 2 infects below
the waist (causing genital sores). This is not completely
true. Both herpes virus type 1 and type 2 can cause
herpes lesions on the lips or genitals, but recurrent cold
sores are almost always type 1. The two viruses seem to
have evolved to infect better at one site or the other,
especially with regard to recurrent disease.
To determine the occurrence of herpes type 2
infection in the United States, the Centers for
Disease Control and Prevention (CDC) used information from a survey called the National Health and
Nutrition Examination Survey III (1988–1994). This
survey of 40,000 noninstitutionalized people found
that 21.9% of persons age 12 or older had antibodies
to herpes type 2. This means that 45 million Americans
have been exposed at some point in their lives to
herpes simplex virus type 2. More women (25.6%)
than men (17.8%) had antibodies. The racial differences for herpes type 2 antibodies were whites, 17.6%;
blacks, 45.9%; and Mexican Americans, 22.3%.
Interestingly, only 2.6% of adults reported that they
have had genital herpes. Over half (50% to 60%) of
the white adults in the United States have antibodies
to herpes simplex virus type 1. The occurrence of
antibodies to herpes type 1 is higher in blacks.
Viruses are different from bacteria. While bacteria
are independent and can reproduce on their own,
viruses cannot reproduce without the help of a cell.
Viruses enter human cells and force them to make
more virus. A human cell infected with herpes virus
releases thousands of new viruses before it is killed.
The cell death and resulting tissue damage causes the
actual sores. The highest risk for spreading the virus is
GALE ENCYCLOPEDIA OF MEDICINE

multiple sexual partners, and a medical history of
other sexually-transmitted diseases.

Herpes virus can also infect a cell and instead of
making the cell produce new viruses, it hides inside the
cell and waits. Herpes virus hides in cells of the nervous system called ‘‘neurons.’’ This is called ‘‘latency.’’
A latent virus can wait inside neurons for days,
months, or even years. At some future time, the virus
‘‘awakens’’ and causes the cell to produce thousands
of new viruses which causes an active infection.
Sometimes an active infection occurs without visible
sores. Therefore, an infected person can spread herpes
virus to other people even in the absence of sores.

Most patients with genital herpes experience a prodrome (symptoms of oncoming disease) of pain, burning, itching, or tingling at the site where blisters will
form. This prodrome stage may last anywhere from a
few hours, to one to two days. The herpes infection
prodrome can occur for both the primary infection
and recurrent infections. The prodrome for recurrent
infections may be severe and cause a severe burning or
stabbing pain in the genital area, legs, or buttocks.

This process of latency and active infection is best
understood by considering the genital sore cycle. An
active infection is obvious because sores are present.
The first infection is called the ‘‘primary’’ infection.
This active infection is then controlled by the body’s
immune system and the sores heal. In between active
infections, the virus is latent. At some point in the
future latent viruses become activated and once
again cause sores. These are called ‘‘recurrent infections’’ or ‘‘outbreaks.’’ Genital sores caused by herpes
type 1 recur much less frequently than sores caused by
herpes type 2.

The first symptoms of herpes usually occur within
two to seven days after contact with an infected person
but may take up to two weeks. Symptoms of the
primary infection are usually more severe than those
of recurrent infections. For up to 70% of the patients,
the primary infection causes symptoms which affect
the whole body (called ‘‘constitutional symptoms’’)
including tiredness, headache, fever, chills, muscle
aches, loss of appetite, as well as painful, swollen
lymph nodes in the groin. These symptoms are greatest during the first three to four days of the infection
and disappear within one week. The primary infection
is more severe in women than in men.

Although it is unknown what triggers latent viruses
to activate, several conditions seem to bring on infections. These include illness, tiredness, exposure to sunlight, menstruation, skin damage, food allergy and hot
or cold temperatures. Although many people believe
that stress can bring on their genital herpes outbreaks,
there is no scientific evidence that there is a link between
stress and recurrences. However, at least one clinical
study has shown a connection between how well people
cope with stress and their belief that stress and recurrent
infections are linked.
Newborn babies who are infected with herpes
virus experience a very severe, and possibly fatal disease. This is called ‘‘neonatal herpes infection.’’ In the
United States, one in 3,000–5,000 babies born will be
infected with herpes virus. Babies can become infected
during passage through the birth canal, but can
become infected during the pregnancy if the membranes rupture early. Doctors will perform a
Cesarean section on women who go into labor with
active genital herpes.

Causes and symptoms
While anyone can be infected by herpes virus, not
everyone will show symptoms. Risk factors for genital
herpes include: early age at first sexual activity,
GALE ENCYCLOPEDIA OF MEDICINE

Primary genital herpes

Following the prodrome come the herpes blisters,
which are similar on men and women. First, small red
bumps appear. These bumps quickly become fluidfilled blisters. In dry areas, the blisters become filled
with pus and take on a white to gray appearance,
become covered with a scab, and heal within two to
three weeks. In moist areas, the fluid-filled blisters burst
and form painful ulcers which drain before healing.
New blisters may appear over a period of one week or
longer and may join together to form very large ulcers.
The pain is relieved within two weeks and the blisters
and ulcers heal without scarring by three to four weeks.
Women can experience a very severe and painful
primary infection. Herpes blisters first appear on the
labia majora (outer lips), labia minora (inner lips), and
entrance to the vagina. Blisters often appear on the
clitoris, at the urinary opening, around the anal opening, and on the buttocks and thighs. In addition,
women may get herpes blisters on the lips, breasts,
fingers, and eyes. The vagina and cervix are almost
always involved which causes a watery discharge.
Other symptoms that occur in women are: painful or
difficult urination (83%), swelling of the urinary tube
(85%), meningitis (36%), and throat infection (13%).
Most women develop painful, swollen lymph nodes
(lymphadenopathy) in the groin and pelvis. About one
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Genital herpes

the time period beginning with the appearance of blisters and ending with scab formation.

Genital herpes

who specialize in skin diseases), urologists (doctors
who specialize in the urinary tract diseases of men
and women and the genital organs of men), gynecologists (doctors who specialize in the diseases of
women’s genital organs) and infectious disease specialists. The diagnosis and treatment of this infectious
disease should be covered by most insurance
providers.

Female cervix covered with herpes
Researchers. Reproduced by permission.)

lesions

(Photo

in ten women get a vaginal yeast infection as a complication of the primary herpes infection.
In men, the herpes blisters usually form on the
penis but can also appear on the scrotum, thighs, and
buttocks. Fewer than half of the men with primary
herpes experience the constitutional symptoms. Thirty
percent to 40% of men have a discharge from the
urinary tube. Some men develop painful swollen
lymph nodes (lymphadenopathy) in the groin and pelvis. Although less frequently than women, men too
may experience painful or difficult urination (44%),
swelling of the urinary tube (27%), meningitis (13%),
and throat infection (7%).
Recurrent genital herpes
One or more outbreaks of genital herpes per year
occur in 60–90% of those infected with herpes virus.
About 40% of the persons infected with herpes simplex virus type 2 will experience six or more outbreaks
each year. Genital herpes recurrences are less severe
than the primary infection; however, women still
experience more severe symptoms and pain than
men. Constitutional symptoms are not usually present. Blisters will appear at the same sites during
each outbreak. Usually there are fewer blisters, less
pain, and the time period from the beginning of symptoms to healing is shorter than the primary infection.
One out of every four women experience painful or
difficult urination during recurrent infection. Both
men and women may develop lymphadenopathy.

Laboratory tests may be performed to look for the
virus. Because healing sores do not shed much virus, a
sample from an open sore would be taken for viral
culture. A sterile cotton swab would be wiped over
open sores and the sample used to infect human cells in
culture. Cells which are killed by herpes virus have a
certain appearance under microscopic examination.
The results of this test are available within two to ten
days. Other areas which may be sampled, depending
upon the disease symptoms in a particular patient,
include the urinary tract, vagina, cervix, throat, eye
tissues, and cerebrospinal fluid.
Direct staining and microscopic examination of the
lesion sample may also be used. A blood test may be
performed to see if the patient has antibodies to herpes
virus. The results of blood testing are available within
one day. The disadvantage of this blood test is that it
usually does not distinguish between herpes type 1 and
2, and only determines that the patient has had a herpes
infection at some point in his or her life. Therefore, the
viral culture test must be performed to be absolutely
certain that the sores are caused by herpes virus.
Because genital sores can be symptoms of many
other diseases, the doctor must determine the exact
cause of the sores. The above mentioned tests are
performed to determine that herpes virus is causing
the genital sores. Other diseases which may cause
genital sores are syphilis, chancroid, lymphogranuloma
venereum, granuloma inguinale, herpes zoster,
erythema multiform, Behçet’s syndrome, inflammatory bowel disease, contact dermatitis, candidiasis,
and impetigo.
Because most newborns who are infected with
herpes virus were born to mothers who had no symptoms of infection it is important to check all newborn
babies for symptoms. Any skin sore should be sampled
to determine if it is caused by herpes simplex. Babies
should be checked for sores in their mouth and for
signs of herpes infection in their eyes.

Diagnosis
Because genital herpes is so common, it is diagnosed primarily by symptoms. It can be diagnosed and
treated by the family doctor, dermatologists (doctors
1604

Treatment
There is no cure for herpes virus infections. There
are antiviral drugs available which have some effect in
GALE ENCYCLOPEDIA OF MEDICINE

Patients with frequent outbreaks (greater than six
to eight per year) may benefit from long term use of
acyclovir which is called ‘‘suppressive therapy.’’
Patients on suppressive therapy have longer periods
between herpes outbreaks. The specific dosage used
for suppression needs to be determined for each
patient and should be reevaluated every few years.
Alternatively, patients may use short term suppressive
therapy to lessen the chance of developing an active
infection during special occasions such as weddings or
holidays.

A close-up view of a man’s penis with a blister (center of
image) caused by the herpes simplex virus. (Photograph by
Dr. P. Marazzi, Custom Medical Stock Photo. Reproduced by
permission.)

lessening the symptoms and decreasing the length of
herpes outbreaks. There is evidence that some may
also prevent future outbreaks. These antiviral drugs
work by interfering with the replication of the viruses
and are most effective when taken as early in the
infection process as possible. For the best results,
drug treatment should begin during the prodrome
stage before blisters are visible. Depending on the
length of the outbreak, drug treatment could continue
for up to 10 days.
Acyclovir (Zovirax) is the drug of choice for
herpes infection and can be given intravenously,
taken by mouth (orally), or applied directly to sores
as an ointment. Acyclovir has been in use for many
years and only five out of 100 patients experience side
effects. Side effects of acyclovir treatment include nausea, vomiting, itchy rash, and hives. Although acyclovir
is the recommended drug for treating herpes infections, other drugs may be used including famciclovir
(Famvir), valacyclovir (Valtrex), vidarabine (Vira-A),
idoxuridine (Herplex Liquifilm, Stoxil), trifluorothymidine (Viroptic), and penciclovir (Denavir).
Acyclovir is effective in treating both the primary
infection and recurrent outbreaks. When taken intravenously or orally, acyclovir reduces the healing time,
virus shedding period, and duration of vesicles. The
standard oral dose of acyclovir for primary herpes is
200 mg five times daily or 400 mg three times daily for
GALE ENCYCLOPEDIA OF MEDICINE

There are several things that a patient may do to
lessen the pain of genital sores. Wearing loose fitting
clothing and cotton underwear is helpful. Removing
clothing or wearing loose pajamas while at home may
reduce pain. Soaking in a tub of warm water and using a
blow dryer on the ‘‘cool’’ setting to dry the infected area
is helpful. Putting an ice pack on the affected area for
10 minutes, followed by five minutes off and then
repeating this procedure may relieve pain. A zinc sulfate
ointment may help to heal the sores. Application of a
baking soda compress to sores may be soothing.
Neonatal herpes
Newborn babies with herpes virus infections are
treated with intravenous acyclovir or vidarabine for 10
days. These drugs have greatly reduced deaths and
increased the number of babies who appear normal
at one year of age. However, because neonatal herpes
infection is so serious, even with treatment babies may
not survive, or may suffer nervous system damage.
Infected babies may be treated with long term suppressive therapy.

Alternative treatment
An imbalance in the amino acids lysine and arginine is thought to be one contributing factor in herpes
virus outbreaks. A ratio of lysine to arginine that is in
balance (that is more lysine than arginine is present)
seems to help the immune system work optimally.
Thus, a diet that is rich in lysine may help prevent
recurrences of genital herpes. Foods that contain
high levels of lysine include most vegetables, legumes,
fish, turkey, beef, lamb, cheese, and chicken. Patients
may take 500 mg of lysine daily and increase to 1,000 mg
three times a day during an outbreak. Intake of the
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Genital herpes

a period of 10 days. Recurrent herpes is treated with
the same doses for a period of five days. Intravenous
acyclovir is given to patients who require hospitalization because of severe primary infections or herpes
complications such as aseptic meningitis or sacral
ganglionitis (inflammation of nerve bundles).

Genital warts

KEY TERMS
Groin—The region of the body that lies between
the abdomen and the thighs.
Latent virus—A nonactive virus which is in a dormant state within a cell. Herpes virus is latent in
cells of the nervous system.
Prodrome—Symptoms which warn of the beginning of disease. The herpes prodrome consists of
pain, burning, tingling, or itching at a site before
blisters are visible.
Recurrence—The return of an active herpes infection following a period of latency.
Ulcer—A painful, pus-draining, depression in the
skin caused by an infection.

amino acid arginine should be reduced. Foods rich in
arginine that should be avoided are chocolate, peanuts, almonds, and other nuts and seeds.
Clinical experience indicates a connection
between high stress and herpes outbreaks. Some
patients respond well to stress reduction and relaxation
techniques. Acupressure and massage may relieve
tiredness and stress. Meditation, yoga, tai chi, and
hypnotherapy can also help relieve stress and promote
relaxation.
Some herbs, including echinacea (Echinacea spp.)
and garlic (Allium sativum), are believed to strengthen
the body’s defenses against viral infections. Red marine algae (family Dumontiaceae), both taken internally and applied topically, is thought to be effective in
treating herpes type I and type II infections. Other
topical treatments may be helpful in inhibiting the
growth of the herpes virus, in minimizing the damage
it causes, or in helping the sores heal. Zinc sulphate
ointment seems to help sores heal and to fight recurrence. Lithium succinate ointment may interfere with
viral replication. An ointment made with glycyrrhizinic acid, a component of licorice (Glycyrrhiza glabra),
seems to inactivate the virus. Topical applications of
vitamin E or tea tree oil (Melaleuca spp.) help dry up
herpes sores. Specific combinations of homeopathic
remedies may also be helpful treatments for genital
herpes.

Prognosis
Although physically and emotionally painful,
genital herpes is usually not a serious disease. The
1606

primary infection can be severe and may require hospitalization for treatment. Complications of the primary infection may involve the cervix, urinary system,
anal opening, and the nervous system. Persons who
have a decreased ability to produce an immune
response to infection (called ‘‘immunocompromised’’)
due to disease or medication are at risk for a very
severe, and possibly fatal, herpes infection. Even with
antiviral treatment, neonatal herpes infections can be
fatal or cause permanent nervous system damage.

Prevention
The only way to prevent genital herpes is to avoid
contact with infected persons. This is not an easy
solution because many people aren’t aware that they
are infected and can easily spread the virus to others.
Avoid all sexual contact with an infected person during a herpes outbreak. Because herpes virus can be
spread at any time, condom use is recommended to
prevent the spread of virus to uninfected partners. As
of early 1998 there were no herpes vaccines available,
although new herpes vaccines are being tested in
humans.
Resources
BOOKS

Ebel, Charles. Managing Herpes: How to Live and Love With a
Chronic STD. American Social Health Association, 1998.

Belinda Rowland, PhD

Genital warts
Definition
Genital warts, which are also called condylomata
acuminata or venereal warts, are growths in the genital
area caused by a sexually transmitted papillomavirus. A
papillomavirus is a virus that produces papillomas, or
benign growths on the skin and mucous membranes.

Description
Genital warts are the most common sexually transmitted disease (STD) in the general population. It is
estimated that 1% of sexually active people between
the ages of 18 and 45 have genital warts; however,
polymerase chain reaction (PCR) testing indicates that
as many as 40% of sexually active adults carry the
human papillomavirus (HPV) that causes genital warts.
GALE ENCYCLOPEDIA OF MEDICINE

Genital warts

Genital warts vary somewhat in appearance. They
may be either flat or resemble raspberries or cauliflower in appearance. The warts begin as small red or
pink growths and grow as large as four inches across,
interfering with intercourse and childbirth. The warts
grow in the moist tissues of the genital areas. In
women, they occur on the external genitals and on
the walls of the vagina and cervix; in men, they develop
in the urethra and on the shaft of the penis. The warts
then spread to the area behind the genitals surrounding the anus.
Risk factors for genital warts include:


multiple sexual partners



infection with another STD



pregnancy



anal intercourse



poor personal hygiene



heavy perspiration

Causes and symptoms
There are about 80 types of human papillomavirus. Genital warts are caused by HPV types 1, 2, 6,
11, 16, and 18. HPV is transmitted by sexual contact.
The incubation period varies from one to six months.
The symptoms include bleeding, pain, and odor as
well as the visible warts.

Man with genital warts. (Custom Medical Stock Photo.
Reproduced by permission.)

KEY TERMS
Condylomata acuminata—Another name for genital warts.
Papilloma—A benign growth on the skin or
mucous membrane. Viruses that cause these
growths are called human papillomaviruses
(HPVs).
Podophyllum resin—A medication derived from
the May apple or mandrake and used to treat genital warts.

Diagnosis
The diagnosis is usually made by examining scrapings from the warts under a darkfield microscope. If
the warts are caused by HPV, they will turn white
when a 5% solution of white vinegar is added. If the
warts reappear, the doctor may order a biopsy to rule
out cancer.

Treatment
No treatment for genital warts is completely effective because therapy depends on destroying skin
infected by the virus. There are no drugs that will kill
the virus directly.
Medications
Genital warts were treated until recently with
applications of podophyllum resin, a corrosive
substance that cannot be given to pregnant patients.
A milder form of podophyllum, podofilox
(Condylox), has been introduced. Women are also
treated with 5-fluorouracil cream, bichloroacetic
GALE ENCYCLOPEDIA OF MEDICINE

acid, or trichloroacetic acid. All of these substances
irritate the skin and require weeks of treatment.
Genital warts can also be treated with injections of
interferon. Interferon works best in combination with
podofilox applications.
Surgery
Surgery may be necessary to remove warts blocking the patient’s vagina, urethra, or anus. Surgical
techniques include the use of liquid nitrogen, electrosurgery, and laser surgery.

Prognosis
Genital warts are benign growths and are not
cancerous by themselves. Repeated HPV infection
in women, however, appears to increase the risk of
later cervical cancer. Women infected with HPV
types 16 and 18 should have yearly cervical smears.
Recurrence is common with all present methods of
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Gestalt therapy

treatment—including surgery—because HPV can
remain latent in apparently normal surrounding skin.

Prevention
The only reliable method of prevention is sexual
abstinence. The use of condoms minimizes but does
not eliminate the risk of HPV transmission. The
patient’s sexual contacts should be notified and
examined.
Resources
BOOKS

Foster, David C. ‘‘Vulvar and Vaginal Disease.’’ In Current
Diagnosis. Vol. 9. edited by Rex B. Conn, et al.
Philadelphia: W. B. Saunders Co., 1997.
MacKay, H. Trent. ‘‘Gynecology.’’ In Current Medical
Diagnosis and Treatment, 1998, edited by Stephen
McPhee, et al., 37th ed. Stamford: Appleton & Lange,
1997.

Rebecca J. Frey, PhD

Gentamicin see Aminoglycosides
German measles see Rubella

Gestalt therapy
Definition
Gestalt therapy is a humanistic therapy technique
that focuses on gaining an awareness of emotions and
behaviors in the present rather than in the past. The
therapist does not interpret experiences for the patient.
Instead, the therapist and patient work together to help
the patient understand him/herself. This type of therapy focuses on experiencing the present situation rather
than talking about what occurred in the past. Patients
are encouraged to become aware of immediate needs,
meet them, and let them recede into the background.
The well-adjusted person is seen as someone who has a
constant flow of needs and is able to satisfy those needs.

Purpose
In Gestalt therapy (from the German word
meaning form), the major goal is self-awareness.
Patients work on uncovering and resolving interpersonal issues during therapy. Unresolved issues are
unable to fade into the background of consciousness
because the needs they represent are never met. In
1608

Gestalt therapy, the goal is to discover people connected with a patient’s unresolved issues and try to
engage those people (or images of those people) in
interactions that can lead to a resolution. Gestalt
therapy is most useful for patients open to working
on self-awareness.

Precautions
The choice of a therapist is crucial. Some people
who call themselves ‘‘therapists’’ have limited training
in Gestalt therapy. It is important that the therapist be
a licensed mental health professional. Additionally,
some individuals may not be able to tolerate the intensity of this type of therapy.

Description
Gestalt therapy has developed into a form of
therapy that emphasizes medium to large groups,
although many Gestalt techniques can be used in
one-on-one therapy. Gestalt therapy probably has a
greater range of formats than any other therapy
technique. It is practiced in individual, couples,
and family therapies, as well as in therapy with
children.
Ideally, the patient identifies current sensations
and emotions, particularly ones that are painful or
disruptive. Patients are confronted with their unconscious feelings and needs, and are assisted to accept
and assert those repressed parts of themselves.
The most powerful techniques involve role-playing.
For example, the patient talks to an empty chair as they
imagine that a person associated with an unresolved
issue is sitting in the chair. As the patient talks to the
‘‘person’’ in the chair, the patient imagines that the
person responds to the expressed feelings. Although
this technique may sound artificial and might make
some people feel self-conscious, it can be a powerful
way to approach buried feelings and gain new insight
into them.
Sometimes patients use battacca bats, padded
sticks that can be used to hit chairs or sofas. Using a
battacca bat can help a patient safely express anger. A
patient may also experience a Gestalt therapy marathon, where the participants and one or more facilitators have nonstop group therapy over a weekend. The
effects of the intense emotion and the lack of sleep can
eliminate many psychological defenses and allow significant progress to be made in a short time. This is
true only if the patient has adequate psychological
strength for a marathon and is carefully monitored
by the therapist.
GALE ENCYCLOPEDIA OF MEDICINE

Gestalt therapy begins with the first contact. There
is no separate diagnostic or assessment period. Instead,
assessment and screening are done as part of the ongoing
relationship between patient and therapist. This assessment includes determining the patient’s willingness and
support for work using Gestalt methods, as well as
determining the compatibility between the patient and
the therapist. Unfortunately, some ‘‘encounter groups’’
led by poorly trained individuals do not provide adequate pre-therapy screening and assessment.

Gestational diabetes
Definition
Gestational diabetes is a condition that occurs during pregnancy. Like other forms of diabetes, gestational
diabetes involves a defect in the way the body processes
and uses sugars (glucose) in the diet. Gestational diabetes, however, has a number of characteristics that are
different from other forms of diabetes.

Description
Aftercare
Sessions are usually held once a week. Frequency
of sessions held is based on how long the patient can go
between sessions without losing the momentum from
the previous session. Patients and therapists discuss
when to start sessions, when to stop sessions, and what
kind of activities to use during a session. However, the
patient is encouraged and required to make choices.

Risks
Disturbed people with severe mental illness may not
be suitable candidates for Gestalt therapy. Facilities that
provide Gestalt therapy and train Gestalt therapists
vary. Since there are no national standards for these
Gestalt facilities, there are no set national standards for
Gestalt therapy or Gestalt therapists.

Normal results
Scientific documentation on the effectiveness of
Gestalt therapy is limited. Evidence suggests that this
type of therapy may not be reliably effective.

Abnormal results
This approach can be anti-intellectual and can discount thoughts, thought patterns, and beliefs. In the
hands of an ineffective therapist, Gestalt procedures
can become a series of mechanical exercises, allowing
the therapist as a person to stay hidden. Moreover, there
is a potential for the therapist to manipulate the patient
with powerful techniques, especially in therapy marathons where fatigue may make a patient vulnerable.
Resources

Glucose is a form of sugar that is present in many
foods, including sweets, potatoes, pasta, and breads.
The body uses glucose to provide energy. It is stored
in the liver, muscles, and fatty tissue. The pancreas
produces a hormone (a chemical produced in one part
of the body, which travels to another part of the body in
order to exert its effect) called insulin. Insulin is required
to allow glucose to enter the liver, muscles, and fatty
tissues, thus reducing the amount of glucose in the
blood. In diabetes, blood levels of glucose remain
abnormally high. In many forms of diabetes, this is
because the pancreas does not produce enough insulin.
In gestational diabetes, the pancreas is not at fault.
Instead, the problem is in the placenta. During pregnancy, the placenta provides the baby with nourishment.
It also produces a number of hormones that interfere
with the body’s usual response to insulin. This condition
is referred to as ‘‘insulin resistance.’’ Most pregnant
women do not suffer from gestational diabetes, because
the pancreas works to produce extra quantities of insulin
in order to compensate for insulin resistance. However,
when a woman’s pancreas cannot produce enough extra
insulin, blood levels of glucose stay abnormally high, and
the woman is considered to have gestational diabetes.
About 1–3% of all pregnant women develop
gestational diabetes. Women at risk for gestational
diabetes include those who:


are overweight



have a family history of diabetes



have previously given birth to a very large, heavy baby



have previously had a baby who was stillborn, or
born with a birth defect



have an excess amount of amniotic fluid (the cushioning fluid within the uterus that surrounds the
developing fetus)



are over 25 years of age



belong to an ethnic group known to experience
higher rates of gestational diabetes (in the United

ORGANIZATIONS

Association for the Advancement of Gestalt Therapy. 400
East 58th St., New York, NY 10022. (212) 486-1581.
<http://www.aagt.org>.

David James Doermann
GALE ENCYCLOPEDIA OF MEDICINE

1609

Gestational diabetes

Preparation

Gestational diabetes

States, these groups include Mexican-Americans,
American Indians, African-Americans, as well as
individuals from Asia, India, or the Pacific Islands)


have a previous history of gestational diabetes during a pregnancy

Causes and symptoms
Most women with gestational diabetes have no
recognizable symptoms. However, leaving gestational
diabetes undiagnosed and untreated is risky to the
developing fetus. Left untreated, a diabetic mother’s
blood sugar levels will be consistently high. This sugar
will cross the placenta and pour into the baby’s system
through the umbilical cord. The unborn baby’s pancreas will respond to this high level of sugar by constantly putting out large amounts of insulin. The
insulin will allow the fetus’s cells to take in glucose,
where it will be converted to fat and stored. A baby
who has been exposed to constantly high levels of sugar
throughout pregnancy will be abnormally large. Such a
baby will often grow so large that he or she cannot be
born through the vagina, but will instead need to be
born through a surgical procedure (cesarean section).
Furthermore, when the baby is born, the baby will
still have an abnormally large amount of insulin circulating. After birth, when the mother and baby are no
longer attached to each other via the placenta and
umbilical cord, the baby will no longer be receiving
the mother’s high level of sugar. The baby’s high level
of insulin, however, will very quickly use up the glucose circulating in the baby’s bloodstream. The baby is
then at risk for having a dangerously low level of blood
glucose (a condition called hypoglycemia).

Diagnosis
Since gestational diabetes most often exists with
no symptoms detectable by the patient, and since its
existence puts the developing baby at considerable
risk, screening for the disorder is a routine part of
pregnancy care. This screening is usually done
between the 24th and 28th week of pregnancy. By
this point in the pregnancy, the placental hormones
have reached a sufficient level to cause insulin resistance. Screening for gestational diabetes involves the
pregnant woman drinking a special solution that contains exactly 50 grams of glucose. An hour later, the
woman’s blood is drawn and tested for its glucose
level. A level less than 140 mg/dl is considered normal.
When the screening glucose level is over 140 mg/dl,
a special three-hour glucose tolerance test is performed.
This involves following a special diet for three days
1610

prior to the test. This diet is set up to contain at least
150 grams of carbohydrates each day. Just before the
test, the patient is instructed to eat and drink nothing
(except water) for 10–14 hours. A blood sample is then
tested to determine the fasting glucose level. The patient
then drinks a special solution containing exactly 100
grams of glucose, and her blood is tested every hour for
the next three hours. If two or more of these levels are
elevated over normal, then the patient is considered to
have gestational diabetes.

Treatment
Treatment for gestational diabetes will depend on
the severity of the diabetes. Mild forms can be treated
with diet (decreasing the intake of sugars and fats, in
particular). Many women are put on strict, detailed
diets, and are asked to stay within a certain range of
calorie intake. Exercise sometimes is used to keep
blood sugar levels lower. Patients often are asked to
regularly measure their blood sugar. This is done by
poking a finger with a needle called a lancet, putting a
drop of blood on a special type of paper, and feeding
the paper into a meter that analyzes and reports the
blood sugar level. In fact self-monitoring of blood
glucose helps manage gestational diabetes and prevent
complications. When diet and exercise do not keep
blood glucose levels within an acceptable range, a
patient may need to take regular shots of insulin.
Many babies born to women with gestational diabetes are large enough to cause more difficult deliveries, and they may require the use of forceps, suction,
or cesarean section. Once the baby is born, it is important to carefully monitor its blood glucose levels.
These levels may drop sharply and dangerously once
the baby is no longer receiving large quantities of
sugar from the mother. When this occurs, it is easily
resolved by giving the baby glucose.

Prognosis
Prognosis for women with gestational diabetes, and
their babies, is generally good. Almost all such women
stop being diabetic after the birth of their baby.
However, some research has shown that nearly 50% of
these women will develop a permanent form of diabetes
within 15 years. The child of a mother with gestational
diabetes has a greater-than-normal chance of developing diabetes sometime in adulthood, also. A woman who
has had gestational diabetes during one pregnancy has
about a 66% chance of having it again during any
subsequent pregnancies. Women who had gestational
diabetes usually are tested for diabetes at the postpartum checkup or after stopping breastfeeding.
GALE ENCYCLOPEDIA OF MEDICINE

Glucose—A form of sugar. The final product of the
breakdown of carbohydrates (starches).
Insulin—A hormone produced by the pancreas that
is central to the processing of sugars and carbohydrates in the diet.
Placenta—An organ that is attached to the inside
wall of the mother’s uterus and to the fetus via the
umbilical cord. The placenta allows oxygen and
nutrients from the mother’s bloodstream to pass
into the unborn baby.

Prevention

are performed and interpreted by radiologists (physicians who specialize in diagnosis and treatment of diseases by means of x rays or related substances).

Purpose
These studies are designed to find the source of
blood loss from the GI tract; that is the stomach, small
bowel, or colon. They work best when bleeding is
either too slow, intermittent, or too rapid to be identified by other means, such as endoscopy, upper GI
series, or barium enema.
They are particularly useful when other methods
have not been able to determine the site or cause of
bleeding.

Precautions

There is no known way to actually prevent diabetes, particularly since gestational diabetes is due to
the effects of normal hormones of pregnancy.
However, the effects of insulin resistance can be best
handled through careful attention to diet, avoiding
becoming overweight throughout life, and participating in reasonable exercise. A 2003 report also linked
smoking to increased risk of gestational diabetes.

Because of the use of radioactive materials, these
studies are best avoided in pregnant patients. Another
important relates to the interpretation of these tests,
whether normal or abnormal. Since these studies are
far from perfect, they can only be used as ‘‘guides’’ as
to the cause or site of bleeding. In most instances,
further studies must be performed to confirm their
findings.

Resources

Description

PERIODICALS

‘‘Self-monitoring of blood glucose Useful for Managing
Gestational Diabetes.’’ Women’s Health Weekly
(August 7, 2003): 42.
‘‘Smoking Tied to Increased Risk of Gestational Diabetes;
Dose Response Relationship.’’ OB GYN News
(September 1, 2003): 5.
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.

Rosalyn Carson-DeWitt, MD
Teresa G. Odle

Bleeding scans are based on the accumulation of
radioactive material as it exits from the vessels during
a bleeding episode. Blood is first withdrawn from the
patient. Then, the blood, along with a radioactive
substance is injected into a vein and over several
hours scans measuring radioactivity are performed.
The studies were initially reported to be very sensitive
and accurate; however, critical evaluation of these
tests have shown them to be less accurate than originally believed.

Preparation
No preparation is needed for these tests. They are
often done on an ‘‘emergency’’ basis.

Aftercare

GI bleeding studies

No special care is needed after the exam.

Definition
GI bleeding studies uses radioactive materials in the
investigation of bleeding from the gastrointestinal (GI)
tract. These studies go under various names such as ‘‘GI
bleeding scans’’ or ‘‘Tagged red blood cell scans.’’ They
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Bleeding scans are free of any risks or side-effects,
aside from the fact that they should best be avoided in
pregnancy.
1611

GI bleeding studies

KEY TERMS

Giardiasis

of bleeding. This is known as a false-negative result. A
patient must be bleeding at the same time the scan is
performed for it to be seen. Therefore, not finding
evidence of a bleeding source during the study, can
be misleading.

Abnormal results
The accumulation of radioactive material indicating a ‘‘leakage’’ of blood from the vessels is abnormal.
The scan gives a rough, though not exact, guide as to
the location of the bleeding. It can tell where the
bleeding may be, but usually not the cause. Thus,
extreme caution and skill is needed in interpreting
these scans, and decisions involving surgery or other
treatment should await more definitive tests.
Resources
BOOKS

Lane, Loren. ‘‘Radionuclide Scanning.’’ In Sleisenger &
Fordtran’s Gastrointestinal and Liver Disease, edited
by Mark Feldman, et al. Philadelphia: W. B. Saunders
Co., 1997.

David Kaminstein, MD

Giant-cell arteritis see Temporal arteritis
Giardia lamblia infection see Giardiasis
A clay model of the human digestive system. (Custom Medical
Stock Photo. Reproduced by permission.)

Giardiasis
KEY TERMS
Endoscope, Endoscopy—An endoscope as used in
the field of gastroenterology is a thin flexible tube
which uses a lens or miniature camera to view
various areas of the gastrointestinal tract. The performance of an exam using an endoscope is
referred by the general term endoscopy. Diagnosis
through biopsies or other means and therapeutic
procedures can be done with these instruments.

Definition
Giardiasis is a common intestinal infection spread
by eating contaminated food, drinking contaminated
water, or through direct contact with the organism that
causes the disease, Giardia lamblia. Giardiasis is found
throughout the world and is a common cause of traveller’s diarrhea. In the United States it is a growing problem, especially among children in childcare centers.

Description
Normal results
A normal exam would fail to show any evidence of
accumulation of radioactive material on the scan.
However, scans may be normal in as many as 70% of
patients who later turn out to have significant causes
1612

Giardia is one of the most common intestinal
parasites in the world, infecting as much as 20% of
the entire population of the earth. It is common in
overcrowded developing countries with poor sanitation and a lack of clean water. Recent tests have found
Giardia in 7% of all stool samples tested nationwide,
indicating that this disease is much more widespread
GALE ENCYCLOPEDIA OF MEDICINE

Giardiasis

than was originally believed. It has been found not
only in humans, but also in wild and domestic animals.
Giardiasis is becoming a growing problem in the
United States, where it affects three times more children than adults. In recent years, giardiasis outbreaks
have been common among people in schools or daycare centers and at catered affairs and large public
picnic areas. Children can easily pass on the infection
by touching contaminated toys, changing tables, utensils, or their own feces, and then touching other people. For this reason, infection spreads quickly through
a daycare center or institution for the developmentally
disabled.
Unfiltered streams or lakes that may be contaminated by human or animal wastes are a common
source of infection. Outbreaks can occur among campers and hikers who drink untreated water from
mountain streams. While 20 million Americans drink
unfiltered city water from streams or rivers, giardiasis
outbreaks from tainted city water have been rare.
Most of these problems have occurred not due to the
absence of filters, but because of malfunctions in city
water treatment plants, such as a temporary drop in
chlorine levels. It is possible to become infected in a
public swimming pool, however, since Giardia can
survive in chlorinated water for about 15 minutes.
During that time, it is possible for an individual to
swallow contaminated pool water and become
infected.

Causes and symptoms
Giardiasis is spread by food or water contaminated by the Giardia lamblia protozoan organism
found in the human intestinal tract and feces. When
the cysts are ingested, the stomach acid degrades the
cysts and releases the active parasite into the body.
Once within the body, the parasites cling to the lining
of the small intestine, reproduce, and are swept into
the fecal stream. As the liquid content of the bowel
dries up, the parasites form cysts, which are then
passed in the feces. Once excreted, the cysts can survive
in water for more than three months. The parasite is
spread further by direct fecal-oral contamination,
such as can occur if food is prepared without adequate
hand-washing, or by ingesting the cysts in water or
food.
Giardiasis is not fatal, and about two-thirds of
infected people exhibit no symptoms. Symptoms will
not occur until between one and two weeks after infection. When present, symptoms include explosive,
watery diarrhea that can last for a week or more and,
in chronic cases, may persist for months. Because the
GALE ENCYCLOPEDIA OF MEDICINE

Giardia Lamblia
Infection with the protozoon Giardia lamblia, shown above,
causes diarrhea in humans. (Illustration by Electronic Illustrators
Group).

infection interferes with the body’s ability to absorb
fats from the intestinal tract, the stool is filled with fat.
Other symptoms include foul-smelling and greasy
feces, stomach pains, gas and bloating, loss of appetite, nausea and vomiting. In cases in which the infection becomeschronic, lasting for months or years,
symptoms might include poor digestion, problems
digesting milk, intermittent diarrhea, fatigue, weakness, and significant weight loss.

Diagnosis
Diagnosis can be difficult because it can be easy to
overlook the presence of the giardia cysts during a
routine inspection of a stool specimen. In the past,
the condition has been diagnosed by examining three
stool samples for the presence of the parasites.
However, because the organism is shed in some stool
samples and not others, the infection may not be discovered using this method.
A newer, more accurate method of diagnosing the
condition is the enzyme-linked immunosorbent assay
1613

Ginkgo biloba

KEY TERMS
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Antigen—A substance (usually a protein) identified
as foreign by the body’s immune system, triggering
the release of antibodies as part of the body’s
defense mechanism.
Enzyme-linked immunosorbent assay (ELISA)—A
laboratory technique used to detect specific antigens or antibodies. It can be used to diagnose
giardiasis.
Giardia lamblia—A type of protozoa with a whiplike tail that infects the human intestinal tract, causing giardiasis. The protozoa will not spread to other
parts of the body.
Immunocompromised—A state in which the
immune system is suppressed or not functioning
properly.

system, malnourished children, and anyone with low
stomach acid.

Prevention
The best way to avoid giardiasis is to avoid drinking untreated surface water, especially from mountain
streams. The condition also can be minimized by practicing the following preventive measures:


thoroughly washing hands before handling food



maintaining good personal cleanliness



boiling any untreated water for at least three minutes



properly disposing of fecal material

Children with severe diarrhea (and others who are
unable to control their bowel habits) should be kept at
home until the stool returns to normal. If an outbreak
occurs in a daycare center, the director should notify
the local health department. Some local health departments require a follow-up stool testing to confirm that
the person is no longer contagious. People not in highrisk settings can return to their routine activities after
recovery.
Resources

(ELISA) that detects cysts and antigen in stool, and is
approximately 90% accurate. While slightly more
expensive, it only needs to be done once and is therefore less expensive overall than the earlier test.

Treatment
Acute giardiasis can usually be allowed to run its
natural course and tends to clear up on its own.
Antibiotics are helpful, however, in easing symptoms
and preventing the spread of infection. Medications
include metronidazole, furazolidone and paromomycin. Healthy carriers with no symptoms do not need
antibiotic treatment. If treatment should fail, the
patient should wait two weeks and repeat the drug
course. Anyone with an impaired immune system
(immunocompromised), such as a person with AIDS,
may need to be treated with a combination of
medications.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
OTHER

Centers for Disease Control. <http://www.cdc.gov/ncidod/
EID/eidtext.htm>.
International Society of Travel Medicine.
<http:www.istm.org>.

Carol A. Turkington

Gigantism see Acromegaly and gigantism
Gilchrist’s disease see Blastomycosis
Gilles de la Tourette’s syndrome see Tourette
syndrome
Gingivitis see Periodontal disease

Prognosis
Giardiasis is rarely fatal, and when treated
promptly, antibiotics usually cure the infection.
While most people respond quickly to treatment,
some have lingering symptoms and suffer with diarrhea and cramps for long periods, losing weight and
not growing well. Those most at-risk for a course like
this are the elderly, people with a weakened immune
1614

Ginkgo biloba
Definition
Ginkgo biloba, known as the maidenhair tree, is
one of the oldest trees on Earth, once part of the flora
GALE ENCYCLOPEDIA OF MEDICINE

Description
Ginkgo trees may grow to 122 ft (37.2 m) tall and
measure 4 ft (1.2 m) in girth. The female trees have a
somewhat pointed shape at the top, like a pyramid.
The male trees are broader at the crown. The bark of
the ornamental ginkgo tree is rough and fissured and
may be an ash to dark-brown in color. Distinctive,
fan-shaped leaves with long stalks emerge from a
sheath on the stem. Leaves are bright green in spring
and summer, and turn to golden yellow in the fall.
Ginkgo trees may take as long as 30 years to flower.
Ginkgo is dioecious, with male and female flowers
blooming on separate trees. Blossoms grow singly
from the axils of the leaf. The female flowers appear
at the end of a leafless branch. The yellow, plumshaped fruits develop an unpleasant scent as they
ripen. They contain an edible inner seed that is available in Asian country marketplaces. Ginkgo’s longevity may be due, in part, to its remarkable resistance
to disease, pollution, and insect damage. Ginkgo trees
are part of the landscape plan in many urban areas
throughout the world. Millions of ginkgo trees, grown
for harvest of the medicinal leaves, are raised on plantations in the United States, France, South Korea, and
Japan, and are exported to Europe for pharmaceutical
processing.

Purpose
Ginkgo leaves, fresh or dry, and seeds, separated
from the outer layer of the fruit, are used medicinally.
Ginkgo has remarkable healing virtues that have been
recorded as far back as 2800 B.C. in the oldest Chinese
materia medica. Ginkgo seeds were traditionally
served to guests along with alcohol drinks in Japan.
An enzyme present in the ginkgo seed has been shown
in clinical research to speed up alcohol metabolism in
the body, underscoring the wisdom of this folk custom. The leaf extract has been used in Asia for
GALE ENCYCLOPEDIA OF MEDICINE

thousands of years to treat allergies, asthma, and bronchitis. It is also valued in Chinese medicine as a heart
tonic, helpful in the treatment of cardiac arrhythmia.
Ginkgo was first introduced to Europe in 1730, and to
North America in 1784 where it was planted as an
exotic garden ornamental near Philadelphia. Ginkgo
medicinal extracts are the primary prescription medicines used in France and Germany.
Ginkgo acts to increase blood flow throughout
the body, particularly cerebral blood flow. It acts as
a circulatory system tonic, stimulating greater tone in
the venous system. The herb is a useful and proven
remedy for numerous diseases caused by restricted
blood flow. European physicians prescribe the extract
for treatment of Raynaud’s disease, a condition of
impaired circulation to the fingers. It is also recommended to treat intermittent claudication, a circulatory
condition that results in painful cramping of the calf
muscles in the leg and impairs the ability to walk.
German herbalists recommend ingesting the extract
for treatment of leg ulcers, and large doses are used
to treat varicose veins. Ginkgo is widely recommended
in Europe for the treatment of stroke. The dried leaf
extract may also act to prevent hemmorrhagic stroke
by strengthening the blood capillaries throughout the
body. In studies of patients with atherosclerotic clogging of the penile artery, long-term therapy with
ginkgo extract has provided significant improvement
in erectile function. Ginkgo extract also acts to eliminate damaging free-radicals in the body, and has been
shown to be effective in treatment of premenstrual
syndrome, relieving tender or painful breasts.
Ginkgo extract has proven benefits to elderly persons. This ancient herb acts to enhance oxygen utilization and thus improves memory, concentration, and
other mental faculties. The herbal extract is used to
treat Alzheimer’s disease. It has been shown to have
beneficial effect on the hippocampus, an area of the
brain affected by Alzheimer’s disease. The herbal
extract has also been shown to significantly improve
long-distance vision and may reverse damage to the
retina of the eye. Studies have also confirmed its value
in the treatment of depression in elderly persons. The
ginkgo extract may provide relief for persons with
headache, sinusitis, and vertigo. It may also help relieve
chronic ringing in the ears known as tinnitus.
The active constituents in the ginkgo tree, known
as ginkgolides, interfere with a blood protein known
as the platelet activating factor, or PAF. Other phytochemicals in ginkgo include flavonoids, biflavonoides,
proanthocyanidins, trilactonic diterpenes (including
the ginkgolides A, B, C, and M), and bilabolide, a
trilactonic sesquiterpene. The therapeutic effects of
1615

Ginkgo biloba

of the Mesozoic period. The ginkgo tree is the only
surviving species of the Ginkgoaceae family. This
ancient deciduous tree may live for thousands of
years. Ginkgo is indigenous to China, Japan, and
Korea, but also thrived in North America and
Europe prior to the Ice Age. This drastic climate
change destroyed the wild ginkgo tree throughout
much of the world. In China, ginkgo was cultivated
in temple gardens as a sacred tree known as bai gou,
thus assuring its survival there for over 200 million
years. Ginkgo fossils found from the Permian period
are identical to the living tree, which is sometimes
called a living fossil.

Ginseng, Korean

Side effects
Severe allergic skin reactions, similar to those
caused by poison ivy, have been reported after contact
with the fruit pulp of ginkgo. Eating even a small
amount of the fruit has caused severe gastrointestinal
irritation in some persons. People with persistent
headaches should stop taking ginkgo. Some patients
on medications for nervous system disease should
avoid ginkgo. It can interact with some other medicines, but clinical information is still emerging.

Interactions
Ginkgo biloba leaves. (Photograph by Robert J. Huffman. Field
Mark Publications. Reproduced by permission.)

this herb have not been attributed to a single chemical
constituent; rather, the medicinal benefits are due to the
synergy between the various chemical constituents. The
standardized extract of ginkgo must be taken consistently to be effective. A period of at least 12 weeks of
use may be required before the beneficial results are
evident.

The chemically active ginkgolides present in the
extract, specifically the ginkgolide B component, act
to reduce the clotting time of blood and may interact
with antithrombotic medicines, including aspirin.
Resources
BOOKS

PDR for Herbal Medicines. Montvale, NJ: Medical
Economics Company, 1998.

Clare Hanrahan

Preparations
Ginkgo’s active principles are dilute in the leaves.
The herb must be processed to extract the active phytochemicals before it is medicinally useful. It would
take an estimated 50 fresh ginkgo leaves to yield one
standard dose of the extract. Dry extracts of the leaf,
standardized to a potency of 24% flavone glycosides
and 6% terpenes, are commercially available. A standard dose is 40 mg, three times daily, though dosages
as high as 240 mg daily are sometimes indicated.
Ginkgo extracts are widely used in Europe where
they are sold in prescription form or over the counter
as an approved drug. This is not the case in the United
States, where ginkgo extract is sold as a food supplement in tablet and capsule form.

Precautions
Ginkgo is generally safe and non-toxic in therapeutic dosages. Exceeding a daily dose of 240 mg of the
dried extract may result in restlessness, diarrhea, and
mild gastrointestinal disorders. Those on anticoagulants should have their doctor adjust their dose or
should avoid ginkgo in order to avoid over-thinning
their blood and hemorrhaging. Ginkgo should be
avoided two days before and one to two weeks after
surgery to avoid bleeding complications.
1616

Ginseng, Korean
Definition
Korean ginseng is one of the most widely used and
acclaimed herbs in the world. Its scientific name is
Panax ginseng, which is the species from which
Chinese, Korean, red, and white ginseng are produced. Chinese and Korean ginseng are the same
plant cultivated in different regions, and have slightly
different properties according to Chinese medicine.
White ginseng is simply the dried or powdered root
of Korean ginseng, while red ginseng is the same root
that is steamed and dried in heat or sunlight. Red
ginseng is said to be slightly stronger and more stimulating in the body than white, according to Chinese
herbalism.

Description
Korean ginseng has had a long and illustrious
history as an herb for health, and has been used for
thousands of years throughout the Orient as a medicine and tonic. Early Chinese medicine texts written in
the first century A.D. mention ginseng, and ginseng
GALE ENCYCLOPEDIA OF MEDICINE

Korean ginseng grows on moist, shaded mountainsides in China, Korea, and Russia. It is a perennial
herb that reaches heights of two or more feet, and is
distinguished by its dark green leaves and red clusters
of berries. The root of the plant is the part valued for
its medicinal properties. The root is long and slender
and sometimes resembles the shape of the human
body. Asian legends claim that this ‘‘man-root’’ has
magical powers for those lucky enough to afford or
find it, and the roots bearing the closest resemblance
to the human body are still the most valuable ones.
The word ren shen in Chinese means roughly ‘‘the
essence of the earth in the shape of a man.’’
Korean ginseng has historically been one of the
most expensive of herbs, as it has been highly in
demand in China and the Far East for centuries.
Wars have been fought in Asia over lands where it
grew wild. Wild Korean ginseng is now nearly extinct
from many regions. Single roots of wild plants have
recently been auctioned in China and New York City
for sums approaching $50,000. Most of the world’s
supply of Korean ginseng is cultivated by farmers in
Korea and China.
Because of the number of herbs sold under the
name of ginseng, there can be some confusion for the
consumer. Korean ginseng is a member of the
Araliaceae family of plants, which also includes closely
related American ginseng (Panax quinquefolius) and
Siberian ginseng (Eleutherococcus senticosus). Both
American and Siberian ginseng are considered by
Chinese herbalists to be different herbs than Korean
ginseng, and are said to have different effects and
healing properties in the body. To add more confusion, there are eight herbs in Chinese medicine which
are sometimes called ginseng, including black ginseng,
purple ginseng, and prince’s ginseng, some of which
are not at all botanically related to Panax ginseng, so
consumers should choose ginseng products with
awareness.

Purpose
The word panax is formed from Greek roots
meaning ‘‘cure-all,’’ and Panax ginseng has long been
considered to be one of the great healing and
GALE ENCYCLOPEDIA OF MEDICINE

strengthening herbs in natural medicine. Ginseng is
classified as an adaptogen, which is a substance that
helps the body adapt to stress and balance itself without causing major side effects. Korean ginseng is used
as a tonic for improving overall health and stamina,
and Chinese herbalists particularly recommend it for
the ill, weak, or elderly. Korean ginseng has long been
asserted to have longevity, anti-senility, and memory
improvement effects in the aged population. As it
helps the body to adapt to stress, athletes may use
ginseng as herbal support during rigorous training.
Korean ginseng generally increases physical and mental energy. It is a good tonic for the adrenal glands,
and is used by those suffering from exhaustion, burnout, or debilitation from chronic illness.
Traditional Chinese medicine also prescribes
Korean ginseng to treat diabetes, and research has
shown that it enhances the release of insulin from the
pancreas and lowers blood sugar levels. Korean ginseng has been demonstrated to lower blood cholesterol
levels. It has also been shown to have antioxidant
effects and to increase immune system activity, which
makes it a good herbal support for those suffering
from cancer and AIDS and other chronic conditions
that impair the immune system. Further uses of
Korean ginseng in Chinese medicine include treatment
of impotence, asthma, and digestive weakness.
Research
Scientists have isolated what they believe are the
primary active ingredients in ginseng, chemicals
termed saponin triterpenoid glycosides, or commonly
called ginsenocides. There are nearly 30 ginsenocides in
Korean ginseng. Much research on Korean ginseng
has been conducted in China, but controlled human
experiments with it have not been easily accessible to
the English-speaking world. Recent research in China
was summarized by Dr. C. Lui in the February 1992
issue of the Journal of Ethnopharmacology, where he
wrote that Panax ginseng was found to contain 28
ginsenocides that ‘‘act on the central nervous system,
cardiovascular system and endocrine secretion, promote immune function, and have effects on anti-aging
and relieving stress.’’
To summarize other research, Korean ginseng has
been shown in studies to have significant effects for the
following.


Physical improvement and performance enhancement for athletes: A study performed over three
years in Germany showed athletes given ginseng
had favorable improvement in several categories
over a control group who took a placebo. Another
1617

Ginseng, Korean

has long been classified by Chinese medicine as a
‘‘superior’’ herb. This means it is said to promote
longevity and vitality. Legends around the world
have touted ginseng as an aphrodisiac and sexual
tonic. Researchers have found a slight connection
between sex drive and consuming ginseng, although
a direct link and the mechanism of action are still
researched and disputed.

Ginseng, Korean

1982 study showed that athletes given ginseng had
improved oxygen intake and faster recovery time
than those given placebos.


Mental performance improvement and mood
enhancement: In general, studies show that ginseng
enhances mental performance, learning time, and
memory. One study of sixteen volunteers showed
improvement on a wide variety of mental tests,
including mathematics. Another study showed that
those performing intricate and mentally demanding
tasks improved performance when given Korean ginseng. Finally, a study has shown improvement of
mood in depression sufferers with the use of ginseng.



Antifatigue and antistress actions: Patients with
chronic fatigue who were given ginseng showed a
statistically significant improvement in physical
tests and in mental attention and concentration,
when compared with those given placebos.



Lowering blood sugar: Animal studies have shown
that ginseng can facilitate the release of insulin from
the pancreas and increase the number of insulin
receptors in the body.



Antioxidant properties: Scientific analysis of ginseng
has shown that it has antioxidant effects, similar to
the effects of vitamins A, C, and E. Thus, ginseng
could be beneficial in combating the negative effects
of pollution, radiation, and aging.



Cholesterol reduction: Some studies have shown that
Korean ginseng reduces total cholesterol and
increases levels of good cholesterol in the body.



Anticancer effects and immune system stimulation:
Several tests have shown that Korean ginseng
increases immune cell activity in the body, including
the activity of T-cells and lymphocytes, which are
instrumental in fighting cancer and other immune
system disorders like AIDS. A Korean study indicates that taking ginseng may reduce the chances of
getting cancer, as a survey of more than 1,800
patients in a hospital in Seoul showed that those
who did not have cancer were more likely to have
taken ginseng regularly than those patients who had
contracted cancer.



Physical and mental improvement in the elderly: One
study showed significant improvement in an elderly
test group in visual and auditory reaction time and
cardiopulmonary function when given controlled
amounts of Korean ginseng. Korean ginseng has
also been shown to alleviate symptoms of
menopause.



Impotence: Studies of human sexual function and
Korean ginseng have been generally inconclusive,

1618

Dried Korean ginseng. (Custom Medical Stock Photo.
Reproduced by permission.)

despite the wide acclaim of ginseng as a sexual
tonic. Tests with lab animals and ginseng have
shown some interesting results, indicating that
Korean ginseng promotes the growth of male reproductive organs, increases sperm and testoterone
levels, and increases sexual activity in laboratory
animals. In general, scientists believe the link
between ginseng and sex drive is due to ginseng’s
effect of strengthening overall health and balancing
the hormonal system.

Preparations
Korean ginseng can be purchased as whole roots,
powder, liquid extracts, and tea. Roots should be
sliced and boiled in water for up to 45 minutes to
extract all the beneficial nutrients. One to five grams
of dry root is the recommended amount for one serving of tea. Herbalists recommend that ginseng not be
boiled in metal pots, to protect its antioxidant properties. Ginseng should be taken between meals for best
assimilation.
Some high quality Korean ginseng extracts and
products are standardized to contain a specified
amount of ginsenosides. The recommended dosage
GALE ENCYCLOPEDIA OF MEDICINE

Adaptogen—Substance that improves the body’s
ability to adapt to stress.
Ginsenocide—Active substances found in ginseng.

for extracts containing four to eight percent of ginsenosides is 100 mg once or twice daily. The recommended dosage for non-standardized root powder or
extracts is 1–2 g daily, taken in capsules or as a tea. It is
recommended that ginseng be taken in cycles and not
continuously; after each week of taking ginseng, a few
days without ingesting the herb should be observed.
Likewise, Korean ginseng should not be taken longer
than two months at a time, after which one month’s
rest period should be allowed before resuming the
cycle again. Chinese herbalists recommend that ginseng be taken primarily in the autumn and winter
months.

Precautions
Consumers should be aware of the different kinds
of ginseng, and which type is best suited for them. Red
Korean ginseng is considered stronger and more stimulating than white, wild ginseng is stronger than
cultivated, and Korean ginseng is generally believed
to be slightly stronger than Chinese. Furthermore,
American and Siberian ginseng have slightly different
properties than Korean ginseng, and consumers
should make an informed choice as to which herb is
best suited for them. Chinese herbalists do not recommend Korean ginseng for those people who have
‘‘heat’’ disorders in their bodies, such as ulcers, high
blood pressure, tension headaches, and symptoms
associated with high stress levels. Korean ginseng is
generally not recommended for those with symptoms
of nervousness, mental imbalance, inflammation, or
fever. Korean ginseng is not recommended for pregnant or lactating women, and women of childbearing
age should use ginseng sparingly, as some studies
imply that it can influence estrogen levels. Also,
Chinese herbalists typically only prescribe ginseng to
older people or the weak, as they believe that younger
and stronger people do not benefit as much from it and
ginseng is ‘‘wasted on the young.’’
Because of the number of and demand for ginseng
products on the market, consumers should search for
a reputable brand, preferably with a standardized percentage of active ingredients. To illustrate the mislabeling found with some ginseng products, Consumer
GALE ENCYCLOPEDIA OF MEDICINE

Reports magazine analyzed ten nationally-distributed
ginseng products in 1995. They found that several of
them lacked significant amounts of ginsenocides,
despite claims on the packaging to the contrary.
Ginseng fraud has led the American Botanical
Council, publisher of HerbalGram magazine, to initiate the Ginseng Evaluation Program, a comprehensive
study and standardization of ginseng products on the
American market. This study and its labeling standards are still under development, and consumers
should watch for it.

Side effects
Korean ginseng acts as a slight stimulant in the
body, and in some cases can cause overstimulation,
irritability, nervousness and insomnia, although strong
side effects are generally rare. Taking too high a
dosage of ginseng, or taking ginseng for too long without a break, can cause ginseng intoxication, for which
symptoms might include headaches, insomnia, seeing
spots, dizziness, shortage of breath and gastrointestinal discomfort. Long term use may cause menstrual
abnormalities and breast tenderness in some women.

Interactions
Those taking hormonal drugs should use ginseng
with care. Ginseng should not be taken with caffeine
or other stimulants as these may increase its stimulatory effects and cause uncomfortable side effects.
Resources
BOOKS

Hobbs, Christopher. Ginseng: The Energy Herb. Loveland,
CO: Botanica Press, 1996.
PERIODICALS

HerbalGram (a quarterly journal of the American Botanical
Council and Herb Research Foundation). P.O. Box
144345, Austin, TX 78714-4345. (800) 373-7105.

Douglas Dupler, MA

Glaucoma
Definition
Glaucoma is a group of eye diseases characterized
by damage to the optic nerve usually due to excessively
high intraocular pressure (IOP).This increased pressure within the eye, if untreated can lead to optic nerve
1619

Glaucoma

KEY TERMS

Glaucoma

damage resulting in progressive, permanent vision
loss, starting with unnoticeable blind spots at the
edges of the field of vision, progressing to tunnel
vision, and then to blindness.

Description
Between two to three million people in the United
States have glaucoma, and 120,000 of those are legally
blind as a result. It is the leading cause of preventable
blindness in the United States and the most frequent
cause of blindness in African-Americans, who are at
about a three-fold higher risk of glaucoma than the
rest of the population. The risk of glaucoma increases
dramatically with age, but it can strike any age group,
even newborn infants and fetuses.
Glaucoma can be classified into two categories:
open-angle glaucoma and narrow-angle glaucoma. To
understand what glaucoma is and what these terms
mean, it is useful to understand eye structure.
Eyes are sphere-shaped. A tough, non-leaky protective sheath (the sclera) covers the entire eye, except
for the clear cornea at the front and the optic nerve at
the back. Light comes into the eye through the cornea,
then passes through the lens, which focuses it onto the
retina (the innermost surface at the back of the eye).
The rods and cones of the retina transform the light
energy into electrical messages, which are transmitted
to the brain by the bundle of nerves known as the
optic nerve.
The iris, the colored part of the eye shaped like a
round picture frame, is between the dome-shaped cornea and the lens. It controls the amount of light that
enters the eye by opening and closing its central hole
(pupil) like the diaphragm in a camera. The iris, cornea, and lens are bathed in a liquid called the aqueous
humor, which is somewhat similar to plasma. This
liquid is continually produced by nearby ciliary tissues
and moved out of the eye into the bloodstream by a
system of drainage canals (called the trabecular meshwork). The drainage area is located in front of the iris,
in the angle formed between the iris and the point at
which the iris appears to meet the inside of the cornea.
Glaucoma occurs if the aqueous humor is not
removed rapidly enough or if it is made too rapidly,
causing pressure to build-up. The high pressure
distorts the shape of the optic nerve and destroys the
nerve. Destroyed nerve cells result in blind spots in
places where the image from the retina is not being
transmitted to the brain.
Open-angle glaucoma accounts for over 90% of
all cases. It is called ‘‘open-angle’’ because the angle
1620

between the iris and the cornea is open, allowing
drainage of the aqueous humor. It is usually chronic
and progresses slowly. In narrow-angle glaucoma,
the angle where aqueous fluid drainage occurs is
narrow, and therefore may drain slowly or may be
at risk of becoming closed. A closed-angle glaucoma
attack is usually acute, occurring when the drainage
area is blocked. This can occur, for example, if the
iris and lens suddenly adhere to each other and the
iris is pushed forward. In patients with very narrow
angles, this can occur when the eyes dilate (e.g.,
when entering a dark room, or if taking certain
medications).
Congenital glaucoma occurs in babies and is the
result of incomplete development of the eye’s drainage
canals during embryonic development. Microsurgery
can often correct the defects or they can be treated
with a combination of medicine and surgery.
One rare form of open-angle glaucoma, normal
tension glaucoma, is different. People with normaltension glaucoma have optic nerve damage in the
presence of normal IOP. As of 1998, the mechanism
of this disease is a mystery but is generally detected
after an examination of the optic nerve. Those at
higher risk for this form of glaucoma are people
with a familial history of normal tension glaucoma,
people of Japanese ancestory, and people with a
history of systemic heart disease such as irregular
heart rhythm.
Glaucoma is also a secondary condition of over 60
widely diverse diseases and can also result from injury,
inflammation, tumor, or in advanced cases of cataract
or diabetes.

Causes and symptoms
Causes
The cause of vision loss in all forms of glaucoma is optic nerve damage. There are many
underlying causes and forms of glaucoma. Most
causes of glaucoma are not known, but it is clear
that a number of different processes are involved,
and a malfunction in any one of them could cause
glaucoma. For example, trauma to the eye could
result in the angle becoming blocked, or, as a person ages, the lens becomes larger and may push
the iris forward. The cause of optic nerve damage
in normal-tension glaucoma is also unknown, but
there is speculation that the optic nerves of these
patients are susceptible to damage at lower pressures than what is usually considered to be abnormally high.
GALE ENCYCLOPEDIA OF MEDICINE

Ophthalmoscopes, hand-held instruments with a
light source, are used to detect optic nerve damage
by looking through the pupil. The optic nerve is
examined for changes; the remainder of the back of
the eye can be examined as well. Other types of lenses
that can be used to examine the back of the eye
may also be used. A slit lamp will allow the doctor
to examine the front of the eye (i.e., cornea, iris,
and lens).
Visual field tests (perimetry) can detect blind spots
in a patient’s field of vision before the patient is aware
of them. Certain defects may indicate glaucoma.
A close-up view of an inflamed eye with acute glaucoma and
an irregularly enlarged pupil. (Custom Medical Stock Photo.
Reproduced by permission.)

It is probable that most glaucoma is inherited. At
least ten defective genes that cause glaucoma have
been identified.
Symptoms
At first, chronic open-angle glaucoma is without
noticeable symptoms. The pressure build-up is gradual and there is no discomfort. Moreover, the vision
loss is too gradual to be noticed and each eye fills-in
the image where its partner has a blind spot. However,
if it is not treated, vision loss becomes evident, and the
condition can be very painful.
On the other hand, acute closed-angle glaucoma is
obvious from the beginning of an attack. The symptoms are, blurred vision, severe pain, sensitivity to
light, nausea, and halos around lights. The normally
clear corneas may be hazy. This is an ocular emergency and needs to be treated immediately.
Similarly, congenital glaucoma is evident at birth.
Symptoms are bulging eyes, cloudy corneas, excessive
tearing, and sensitivity to light.

Diagnosis
Intraocular pressure, visual field defects, the angle
in the eye where the iris meets the cornea, and the
appearance of the optic nerve are all considered in
the diagnosis of glaucoma. IOP is measured with an
GALE ENCYCLOPEDIA OF MEDICINE

Another test, gonioscopy, can distinguish between
narrow-angle and open-angle glaucoma. A gonioscope, which is a hand-held contact lens with a mirror,
allows visualization of the angle between the iris and
the cornea.
Intraocular pressure can vary throughout the day.
For that reason, the doctor may have a patient return
for several visits to measure the IOP at different times
of the day.

Treatment
Medications
When glaucoma is diagnosed, drugs, typically
given as eye drops, are usually tried before surgery.
Several classes of medications are effective at lowering
IOP and thus preventing optic nerve damage in
chronic and neonatal glaucoma. Beta blockers, like
Timoptic; carbonic anhydrase inhibitors, like acetazolamide; and alpha-2 agonists, such as Alphagan, inhibit the production of aqueous humor. Miotics, like
pilocarpine, and prostaglandin analogues, like
Xalatan, increase the outflow of aqueous humor.
Cosopt is the first eyedrop that is a combined beta
blocker (Timoptic) and carbonic anhydrase inhibitor
and may be helpful for patients required to take more
than one glaucoma medication each day. The Food
and drug administration recently approved two new
prostaglandin-related drugs, Travatan and Lumigan
on March 16, 2001. These drugs work by decreasing
intraocular pressure and may be considered for people
with glaucoma that are unable to tolerate other IOP
1621

Glaucoma

instrument known as a tonometer. One type of tonometer involves numbing the eye with an eyedrop that
has a yellow coloring in it and touching the cornea
with a small probe. This quick test is a routine part of
an eye examination and is usually included without
extra charge in the cost of a visit to an ophthalmologist
or optometrist.

Glaucoma

lowering drugs. Additionally, Travatan may work best
for African-Americans with glaucoma (a population
at high risk for glaucoma).
It is important for patients to tell their doctors
about any conditions they have or medications they
are taking. Certain drugs used to treat glaucoma
should not be prescribed for patients with pre-existing
conditions. Some of these drugs mentioned have side
effects, so patients taking them should be monitored
closely, especially for cardiovascular, pulmonary, and
behavioral symptoms. Different medications lower
IOP by different amounts, and a combination of medications may be necessary. It is important that patients
take their medications and that their regimens are
monitored regularly, to be sure that the IOP is lowered
sufficiently. IOP should be measured three to four
times per year.
Normal-tension glaucoma is treated in the same
way as chronic high-intraocular-pressure glaucoma.
This reduces IOP to less-than-normal levels, on the
theory that overly susceptible optic nerves are less
likely to be damaged at lower pressures. Research
underway may point to better treatments for this
form of glaucoma.
Attacks of acute closed-angle glaucoma are medical emergencies. IOP is rapidly lowered by successive
deployment of acetazolamide, hyperosmotic agents,
a topical beta-blocker, and pilocarpine. Epinephrine
should not be used because it exacerbates angle
closure.

Alternative treatment
Vitamin C, vitamin B1 (thiamine), chromium,
zinc,bilberry and rutin may reduce IOP.
There is evidence that medicinal marijuana lowers
IOP, too. However, marijuana has serious side effects
and contains carcinogens, and any IOP-lowering
medication must be taken continually to avoid optic
nerve damage. Although the Food and Drug
Administration (FDA) and National Institutes of
Health (NIH) currently recommend against treating
glaucoma with marijuana, they are supporting
research to learn more about it and to determine the
feasibility of separating the components that lower
IOP from components that produce side effects and
carcinogens.
Any glaucoma patient using alternative methods
to attempt to prevent optic nerve damage should also
be under the care of a traditionally trained ophthalmologist or optometrist who is licensed to treat glaucoma, so that IOP and optic nerve damage can be
monitored.

Prognosis
About half of the people stricken by glaucoma are
not aware of it. For them, the prognosis is not good,
and many of them will become blind. Sight lost due to
glaucoma cannot be restored. On the other hand, the
prognosis for treated glaucoma is excellent.

Prevention
Surgery
There are several types of laser surgery used to
treat glaucoma. Laser peripheral iridotomy makes an
opening in the iris allowing the fluid to drain, argon
laser trabeculoplasty is aimed at the fluid channel
opening to help the drainage system function and
laser cyclophotocoagulation is used to decrease the
amount of fluid made. Microsurgery, also called ‘‘filtering surgery’’ has been used in many different types
of glaucoma. A new opening is created in the sclera
allowing the intraocular fluid to bypass the blocked
drainage canals. The tissue over this opening forms a
little blister or bleb on the clear conjuctiva that
Doctors monitor ensuring that fluid is draining.
These surgeries are usually successful, but the effects
often last less than a year. Nevertheless, they are an
effective treatment for patients whose IOP is not sufficiently lowered by drugs and for those who can’t
tolerate the drugs. Because all surgeries have risks,
patients should speak to their doctors about the procedure being performed.
1622

Because glaucoma may not initially result in
symptoms, the best form of prevention is to have
regular eye exams.
Patients with narrow angles should avoid certain
medications (even over-the-counter medications, such
as some cold or allergy medications).Any person who
is glaucoma-susceptible (i.e. narrow angles and borderline IOPs) should read the warning labels on overthe-counter medicines and inform their physicians of
products they are considering taking.Steroids may
also raise IOP, so patients may need to be monitored
more frequently if it is necessary to use steroids for
another medical condition.
Not enough is known about the underlying
mechanisms of glaucoma to prevent the disease itself.
However, prevention of optic nerve damage from
glaucoma is essential and can be effectively accomplished when the condition is diagnosed and treated.
As more is learned about the genes that cause glaucoma, it will become possible to test DNA and identify
GALE ENCYCLOPEDIA OF MEDICINE

Agonist—A drug that mimics one of the body’s own
molecules.
Alpha-2 agonist (alpha-2 adrenergic receptor agonist)—A class of drugs that bind to and stimulate alpha2 adrenergic receptors, causing responses similar to
those of adrenaline and noradrenaline. They inhibit
aqueous humor production and a have a wide variety
of effects, including dry mouth, fatigue, and drowsiness.
Aqueous humor—A transparent liquid, contained
within the eye, that is composed of water, sugars,
vitamins, proteins, and other nutrients.

blood, which then pulls water from the eye into the
blood.
Iris—The colored part of the eye just behind the
cornea and in front of the lens that controls the
amount of light sent to the retina.

Betablocker (beta-adrenergic blocker)—A class of
drugs that bind beta-adrenergic receptors and thereby
decrease the ability of the body’s own natural epinephrine to bind to those receptors, leading to inhibition of various processes in the body’s sympathetic
system. Betablockers can slow the heart rate, constrict
airways in the lungs, lower blood pressure, and
reduce aqueous secretion by ciliary tissues in the eye.
Carbonic anhydrase inhibitor—A class of diuretic
drugs that inhibit the enzyme carbonic anhydrase,
an enzyme involved in producing bicarbonate,
which is required for aqueous humor production by
the ciliary tissues in the eye. Thus, inhibitors of this
enzyme inhibit aqueous humor production. Some
side effects are urinary frequency, kidney stones,
loss of the sense of taste, depression, and anemia.
Cornea—Clear, bowl-shaped structure at the front of
the eye. It is located in front of the colored part of the
eye (iris). The cornea lets light into the eye and partially focuses it.
Gonioscope—An instrument used to examine the
trabecular meshwork; consists of a magnifier and a
lens equipped with mirrors, which sits on the
patient’s cornea.

Laser peripheral iridotomy—This procedure makes a
drainage hole in the iris allowing the fluid to drain
from the eye

Hyperosmotic drugs—Refers to a class of drugs for
glaucoma that increase the osmotic pressure in the

potential glaucoma victims, so they can be treated
even before their IOP becomes elevated.
Bonny McClain

Glaucoma surgery see Trabeculectomy
Glioma see Brain tumor
Glipizide see Antidiabetic drugs
GALE ENCYCLOPEDIA OF MEDICINE

Lens (the crystalline lens)—A transparent structure in
the eye that focuses light onto the retina.
Laser cyclophotocoagulation—A procedure used for
severe glaucoma in patients who have not responded
well to previous treatments. The laser partially
destroys the tissues that make the fluid of the eye.

Laser Trabeculoplasty—In this procedure the laser
attempts to open the normal drainage channels of
the eye so fluid can drain more effectively.
Miotic—A drug that causes pupils to contract.
Ophthalmoscope—An instrument, with special lighting, designed to view structures in the back of the eye.
Optic nerve—The nerve that carries visual messages
from the retina to the brain.
Prostaglandin—A group of molecules that exert local
effects on a variety of processes including fluid balance, blood flow, and gastrointestinal function.
Prostaglandin analogue—A class of drugs that are
similar in structure and function to prostaglandin.
Retina—The inner, light-sensitive layer of the eye
containing rods and cones.
Sclera—The tough, fibrous, white outer protective
covering that surrounds the eye.
Tonometry—The measurement of pressure.
Trabecular meshwork—A sponge-like tissue located
near the cornea and iris that functions to drain the
aqueous humor from the eye into the blood.

Glomerulonephritis
Definition
Acute glomerulonephritis is an inflammatory
disease of both kidneys predominantly affecting children from ages two to 12. Chronic glomerulonephritis can develop over a period of 10–20 years and
is most often associated with other systemic disease,
1623

Glomerulonephritis

KEY TERMS

Glomerulonephritis

including diabetes, malaria, hepatitis, or systemic
lupus erythematosus.

Description
Acute glomerulonephritis is an inflammation
of the glomeruli, bundles of tiny vessels inside the
kidneys. The damaged glomeruli cannot effectively
filter waste products and excess water from the bloodstream to make urine. The kidneys appear enlarged,
fatty, and congested.

Causes and symptoms
Acute glomerulonephritis most often follows a
streptococcal infection of the throat or skin. In children, it is most often associated with an upper respiratory infection, tonsillitis, or scarlet fever. Kidney
symptoms usually begin two to three weeks after the
initial infection. Exposure to certain paints, glue or
other organic solvents may also be the causative
agent. It is thought that the kidney is damaged with
exposure to the toxins that are excreted into the urine.
Mild glomerulonephritis may produce no symptoms, and diagnosis is made with laboratory studies of
the urine and blood. Individuals with more severe
cases of the disease may exhibit:


fatigue



nausea and vomiting



shortness of breath



disturbed vision



high blood pressure



swelling, especially noted in the face, hands, feet, and
ankles



blood and protein in the urine, resulting in a smoky
or slightly red appearance

The individual with chronic glomerulonephritis
may discover their condition with a routine physical
exam revealing high blood pressure, or an eye exam
showing vascular or hemorrhagic changes. The kidneys may be reduced to as little as one-fifth their
normal size, consisting largely of fibrous tissues.

Diagnosis
Diagnosis of glomerulonephritis is established
based on medical history, combined with laboratory
studies. A ‘‘dipstick’’ test of urine will reveal increased
protein levels. A 24 hour urine collection allows measurement of the excretion of proteins and creatinine.
Creatinine clearance from the bloodstream by the
1624

A close-up view of glomerulonephritis affecting the kidney.
(Custom Medical Stock Photo. Reproduced by permission.)

kidneys is considered an index of the glomerular filtration rate. Blood studies may reveal a low blood count,
and may also be checked for the presence of a streptococcal antibody titer(a sophisticated blood test indicating presence of streptococcal infection). A kidney
biopsy may also be performed, using ultrasound to
guide the needle for obtaining the specimen.

Treatment
The main objectives in the treatment of acute
glomerulonephritis are to:


decrease the damage to the glomeruli



decrease the metabolic demands on the kidneys



improve kidney function

Bedrest helps in maintaining adequate blood flow to
the kidney. If residual infection is suspected, antibiotic
therapy may be needed. In the presence of fluid overload, diuretics may be used to increase output with urination. Iron and vitamin supplements may be ordered if
anemia develops, and antihypertensives, if high blood
pressure accompanies the illness. In order to rest the
kidney during the acute phase, decreased sodium and
protein intake may be recommended. The amount of
protein allowed is dependent upon the amount lost in the
urine, and the requirements of the individual patient.
Sodium limitations depend on the amount of edema
present. Fluid restrictions are adjusted according to the
patient’s urinary output and body weight.
An accurate daily record of the patient’s weight,
fluid intake and urinary output assist in estimating
kidney function. The patient must be watched for
signs of complications and recurrent infection. As
edema is reduced and the urine becomes free of protein
and red blood cells, the patient is allowed to increase
GALE ENCYCLOPEDIA OF MEDICINE

Dialysis—A process of filtering and removing waste
products from the bloodstream. Two main types are
hemodialysis and peritoneal dialysis. In hemodialysis, the blood flows out of the body into a machine that
filters out the waste products and routes the cleansed
blood back into the body. In peritoneal dialysis, the
cleansing occurs inside the body. Dialysis fluid is
injected into the peritoneal cavity and wastes are
filtered through the peritoneum, the thin membrane
that surrounds the abdominal organs.
Glomeruli—Groups of tiny blood vessels with very
thin walls that function as filters in the kidney.
Glomeruli become inflamed and are destroyed in
the disease process of glomerulonephritis.
Renal—Relating to the kidneys, from the Latin
word renes.

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.
National Kidney Foundation and Urologic Diseases
Information Clearinghouse. 3 Information Way,
Bethesda, MD 20892-3580. (800) 891-5390. <http://
www.niddk.nih.gov/health/kidney/nkudic.htm>.

Kathleen D. Wright, RN

Glossopharyngeal neuralgia see Neuralgia

Glucose-6-phosphate
dehydrogenase deficiency
Definition

activity. A woman who has had glomerulonephritis
requires special medical attention during pregnancy.

Prognosis
In acute glomerulonephritis, symptoms usually
subside in two weeks to several months, with 90% of
children recovering without complications and adults
recovering more slowly. Chronic glomerulonephritis is
a disease that tends to progress slowly, so that there
are no symptoms until the kidneys can no longer
function. The resultant renal failure may require dialysis or kidney transplant.

Prevention
Prevention of glomerulonephritis is best accomplished by avoiding upper respiratory infections, as
well as other acute and chronic infections, especially
those of a streptococcal origin. Cultures of the infection site, usually the throat, should be obtained and
antibiotic sensibility of the offending organism determined. Prompt medical assessment for necessary antibiotic therapy should be sought when infection is
suspected. The use of prophylactic immunizations is
recommended as appropriate.
Resources
ORGANIZATIONS

American Association of Kidney Patients. 100 S. Ashley Dr.,
#280, Tampa, FL 33602. (800) 749-2257. <http://
www.aakp.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Glucose-6-phosphate dehydrogenase deficiency is
an inherited condition caused by a defect or defects in
the gene that codes for the enzyme, glucose6-phosphate dehydrogenase (G6PD). It can cause
hemolytic anemia, varying in severity from life-long
anemia, to rare bouts of anemia to total unawareness
of the condition. The episodes of hemolytic anemia are
usually triggered by oxidants, infection, or by eating
fava beans.

Description
G6PD deficiency is the most common enzyme deficiency in the world, with about 400 million people living
with it. It is most prevalent in people of African,
Mediterranean, and Asian ancestry. The incidence in
different populations varies from zero in South
American Indians to less than 0.1% of Northern
Europeans to about 50% of Kurdish males. In the
United States, it is most common among African
American males; about 11 to 14% are G6PD-deficient.
G6PD deficiency is a recessive sex-linked trait.
Thus, males have only one copy of the G6PD gene,
but females have two copies. Recessive genes are
masked in the presence of a gene that encodes normal
G6PD. Accordingly, females with one copy of the gene
for G6PD deficiency are usually normal, while males
with one copy have the trait.
G6PD is present in all human cells but is particularly important to red blood cells. It is required to
make NADPH in red blood cells but not in other
cells. It is also required to make glutathione.
1625

Glucose-6-phosphate dehydrogenase deficiency

KEY TERMS

Glucose-6-phosphate dehydrogenase deficiency

Glutathione and NADPH both help protect red blood
cells against oxidative damage. Thus, when G6PD is
defective, oxidative damage to red blood cells readily
occurs, and they break open as a result. This event is
called hemolysis, and multiple hemolyses in a short
time span constitute an episode of hemolytic anemia.



Class 3–moderate to mild enzyme deficiency with
10–60% of normal activity



Class 4–very mild or no enzyme deficiency



Class 5–increased enzyme activity Fortunately, only
a small number of people fall into Class 1.

As of 1998, there are almost 100 different known
forms of G6PD enzyme molecules encoded by defective G6PD genes, yet not one of them is completely
inactive. This suggests that G6PD is indispensable.
Many G6PD defective enzymes are deficient in their
stability rather than their initial ability to function.
Since red blood cells lack nuclei, they, unlike other
cells, cannot synthesize new enzyme molecules to
replace defective ones. Hence, we expect young red
blood cells to have new, functional G6PD and older
cells to have non-functioning G6PD. This explains
why episodes of hemolytic anemia are frequently selflimiting; new red blood cells are generated with
enzymes able to afford protection from oxidation.

The major symptoms of hemolytic anemia are
jaundice, dark urine, abdominal pain, back pain, lowered red blood cell count, and elevated bilirubin.
People who suffer from severe and chronic forms of
G6PD deficiency in addition may have gallstones,
enlarged spleens, defective white blood cells, and
cataracts.

The geographic distribution of G6PD deficiency,
allowing for migration, coincides with the geographic
distribution of malaria. This fact and survival statistics
suggest that G6PD deficiency protects against
malaria.
Glucose-6-phosphate dehydrogenase deficiency is
also known as G6PD deficiency, favism, and primaquine sensitivity.

Attacks of hemolytic anemia are serious for
infants. Brain damage and death are possible but
preventable outcomes. Newborns with G6PD
deficiency are about 1.5 times as likely to get neonatal jaundice than newborns without G6PD
deficiency.

Diagnosis
Blood tests can detect G6PD deficiency, either by
measuring the G6PD enzyme activity between episodes or by measuring bilirubin during an episode.
Such tests cost about $50.00. Family histories are helpful, too.

Treatment
Causes and symptoms
Causes
G6PD deficiency is caused by one copy of a defective G6PD gene in males or two copies of a defective
G6PD gene in females. Hemolytic anemic attacks can
be caused by oxidants, infection, and or by eating fava
beans.
Symptoms
The most significant consequence of this disorder
is hemolytic anemia, which is usually episodic, but the
vast majority of people with G6PD deficiency have no
symptoms.
The many different forms of G6PD deficiency
have been divided into five classes according to
severity.


Class 1–enzyme deficiency with chronic hemolytic
anemia



Class 2–severe enzyme deficiency with less than 10%
of normal activity

1626

In a typical attack of hemolytic anemia, no
treatment is needed; the patient will recover in
about eight days. However, blood transfusions are
necessary in severe cases. Recent success treating
elevated bilirubin in newborns by exposing them
to bright light has decreased the need for neonatal
transfusions.

Alternative treatment
Vitamin E and folic acid (both anti-oxidants)
may help decrease hemolysis in G6PD-deficient
individuals.

Prognosis
The prognosis for almost everyone with G6PD
deficiency is excellent. Large studies have shown that
G6PD-deficient individuals do not acquire any illnesses more frequently than the rest of the population. In fact the opposite may be true for some
diseases like ischemic heart disease and cerebrovascular disease.
GALE ENCYCLOPEDIA OF MEDICINE

Bilirubin—A breakdown product derived from
hemoglobin; removed from the blood by the liver.
Enzyme—A protein catalyst; one of the two kinds of
biological catalysts, which are exceedingly specific; each different enzyme only catalyzes one or
two specific reactions.
Enzyme activity—A measure of the ability of an
enzyme to catalyze a specific reaction.
Glutathione—A molecule that acts as a co-enzyme
in cellular oxidation-reduction reactions.
Hemolysis—Lysis (opening) of red blood cells, with
concomitant leakage of cell contents from the cells.

G6PD-deficient babies won’t be subjected to any of
the triggers of hemolytic anemia. Pregnant women,
especially in areas where G6PD deficiency is prevalent, should avoid eating fava beans.
Resources
ORGANIZATIONS

Alliance of Genetic Support Groups. 4301 Connecticut Ave.
NW, Suite 404, Washington, D.C. 20008. (202) 9665557. Fax: (202) 966-8553. <http://
www.geneticalliance.org>.
OTHER

Favism Home Page. <http://rialto.com/favism/
index.htm>.

Lorraine Lica, PhD

Hemolytic anemia—Anemia due to hemolysis.
Jaundice—Yellowish skin color due to liver
disease.
Neonatal—Describes babies just after they are born.
Recessive trait—An inherited trait that is outwardly
obvious only when two copies of the gene for that
trait are present–as opposed to a dominant trait
where one copy of the gene for the dominant trait
is sufficient to display the trait. The recessive condition is said to be masked by the presence of the
dominant gene when both are present; i.e., the
recessive condition is seen only in the absence of
the dominant gene.
Sex-linked—Refers to genes or traits carried on one
of the sex chromosomes, usually the X.
X chromosome—One of the two types of sex chromosomes, present twice in female cells and once in
male cells.

Prevention
Most episodes of hemolytic anemia can be prevented by avoiding fava beans, oxidant drugs, and
oxidant chemicals. All of the following oxidants can
trigger attacks: acetanilid, dapsone, doxorubicin, furazolidone, methylene blue, nalidixic acid, napthalene,
niridazole, nitrofurantoin, phenazopyridine, phenylhydrazine, primaquine, quinidine, quinine, sulfacetamide, sulfamethoxazole, sulfonamide, sulfapyridine,
thiazolesulfone, toluidine blue, and trinitrotoluene.
Since infections also trigger hemolytic attacks and
have other dire consequences, sometimes it is advisable to use one of the listed drugs.
It is especially important to screen newborns who
are likely to have G6PD deficiency to ensure that
GALE ENCYCLOPEDIA OF MEDICINE

Glucosylcerebroside lipidosis see Gaucher
disease
Gluten enteropathy see Celiac disease
Glyburide see Antidiabetic drugs

Glycogen storage diseases
Definition
Glycogen serves as the primary fuel reserve for the
body’s energy needs. Glycogen storage diseases, also
known as glycogenoses, are genetically linked metabolic disorders that involve the enzymes regulating
glycogen metabolism. Symptoms vary by the glycogen
storage disease (GSD) type and can include muscle
cramps and wasting, enlarged liver, and low blood
sugar. Disruption of glycogen metabolism also affects
other biochemical pathways as the body seeks alternative fuel sources. Accumulation of abnormal metabolic by-products can damage the kidneys and other
organs. GSD can be fatal, but the risk hinges on the
type of GSD.

Description
Most of the body’s cells rely on glucose as an
energy source. Glucose levels in the blood are very
stringently controlled within a range or 70–100 mg/
dL, primarily by hormones such as insulin and glucagon. Immediately after a meal, blood glucose levels
rise and exceed the body’s immediate energy requirements. In a process analogous to putting money in the
bank, the body bundles up the extra glucose and stores
1627

Glycogen storage diseases

KEY TERMS

Glycogen storage diseases

it as glycogen in the liver and muscles. Later, as the
blood glucose levels begin to dip, the body makes a
withdrawal from its glycogen savings.
The system for glycogen metabolism relies on a
complex system of enzymes. These enzymes are
responsible for creating glycogen from glucose, transporting the glycogen to and from storage areas within
cells, and extracting glucose from the glycogen as
needed. Both creating and tearing down the glycogen
macromolecule are multistep processes requiring a
different enzyme at each step. If one of these enzymes
is defective and fails to complete its step, the process
halts. Such enzyme defects are the underlying cause of
GSDs.
The enzyme defect arises from an error in its gene.
Since the error is in the genetic code, GSDs can be
passed
down
from
generation-to-generation.
However, all but one GSD are linked to autosomal
genes, which means a person inherits one copy of the
gene from each parent. Following a Mendelian inheritance pattern, the normal gene is dominant and the
defective gene is recessive. As long as a child receives at
least one normal gene, there is no risk for a GSD.
GSDs appear only if a person inherits a defective
gene from both parents.
The most common forms of GSD are Types I, II,
III, and IV, which may account for more than 90% of
all cases. The most common form is Type I, or von
Gierke’s disease, which occurs in one out of every
100,000 births. Other forms, such as Types VI and
IX, are so rare that reliable statistics are not available.
The overall frequency of all forms of glycogen storage
disease is approximately one in 20,000–25,000
live births.

and uric acid in the blood. Growth is impaired, puberty is often delayed, and bones may be weakened by
osteoporosis. Blood platelets are also affected and
frequent nosebleeds and easy bruising are common.
Primary symptoms improve with age, but after age
20–30, liver tumors, liver cancer, chronic renal disease, and gout may appear.


Type Ib is caused by glucose-6-phosphatase translocase deficiency. In order to carry out the final step of
glycogenolysis, glucose-6-phosphate has to be transported into a cell’s endoplasmic reticulum. If translocase, the enzyme responsible for that movement, is
missing or defective, the same symptoms occur as in
Type Ia. Additionally, the immune system is weakened and victims are susceptible to bacterial infections, such as pneumonia, mouth and gum infections,
and inflammatory bowel disease. Types Ic and Id are
also caused by defects in the translocase system.



Type II, or Pompe’s disease or acid maltase deficiency, is caused by lysosomal alpha-D-glucosidase
deficiency in skeletal and heart muscles. GSD II is
subdivided according to the age of onset. In the
infantile form, infants seem normal at birth, but
within a few months they develop muscle weakness,
trouble breathing, and an enlarged heart. Cardiac
failure and death usually occur before age 2, despite
medical treatment. The juvenile and adult forms of
GSD II affect mainly the skeletal muscles in the
body’s limbs and torso. Unlike the infantile form,
treatment can extend life, but there is no cure.
Respiratory failure is the primary cause of death.



Type III, or Cori’s disease, is caused by glycogen
debrancher enzyme deficiency in the liver, muscles,
and some blood cells, such as leukocytes and erythrocytes. About 15% of GSD III cases only involve
the liver. The glycogen molecule is not a simple
straight chain of linked glucose molecules, but rather
an intricate network of short chains that branch off
from one another. In glycogenolysis, a particular
enzyme is required to unlink the branch points.
When that enzyme fails, symptoms similar to GSD I
occur; in childhood, it may be difficult to distinguish
the two GSDs by symptoms alone. In addition to the
low blood sugar, retarded growth, and enlarged liver
causing a swollen abdomen, GSD III also causes
muscles prone to wasting, an enlarged heart, and
heightened levels of lipids in the blood. The muscle
wasting increases with age, but the other symptoms
become less severe.



Type IV, or Andersen’s disease, is caused by glycogen brancher enzyme deficiency in the liver, brain,
heart, skeletal muscles, and skin fibroblasts. The

Causes and symptoms
GSD symptoms depend on the enzyme affected.
Since glycogen storage occurs mainly in muscles and
the liver, those sites display the most prominent
symptoms.
There are at least 10 different types of GSDs
which are classified according to the enzyme affected:


Type Ia, or von Gierke’s disease, is caused by glucose-6-phosphatase deficiency in the liver, kidney,
and small intestine. The last step in glycogenolysis,
the breaking down of glycogen to glucose, is the
transformation of glucose-6-phosphate to glucose.
In GSD I, that step does not occur. As a result, the
liver is clogged with excess glycogen and becomes
enlarged and fatty. Other symptoms include low
blood sugar and elevated levels of lactate, lipids,

1628

GALE ENCYCLOPEDIA OF MEDICINE





Type V, or McArdle’s disease, is caused by glycogen
phosphorylase deficiency in skeletal muscles. Under
normal circumstances, muscles cells rely on oxidation of fatty acids during rest or light activity. More
demanding activity requires that they draw on their
glycogen stockpile. In GSD V, this form of glycogenolysis is disabled and glucose is not available. The
main symptoms are muscle weakness and cramping
brought on by exercise, as well as burgundy-colored
urine after exercise due to myoglobin (a breakdown
product of muscle) in the urine.
Type VI, or Hers’ disease, is caused by liver phosphorylase deficiency, which blocks the first step of
glycogenolysis. In contrast to other GSDs, Type VI
seems to be linked to the X chromosome. Low blood
sugar is one of the key symptoms, but it is not as
severe as in some other forms of GSD. An enlarged
liver and mildly retarded growth also occur.



Type VII, or Tarui’s disease, is caused by muscle
phosphofructokinase deficiency. Although glucose
may be available as a fuel in muscles, the cells cannot
metabolize it. Therefore, abnormally high levels of
glycogen are stockpiled in the muscle cells. The
symptoms are similar to GSD V, but also include
anemia and increased levels of uric acid.



Types VIII and XI are caused by defects of enzymes
in the liver phosphorylase activating-deactivating
cascade and have symptoms similar to GSD VI.



Type IX is caused by liver glycogen phosphorylase
kinase deficiency and, symptom-wise, is very similar
to GSD VI. The main differences are that the symptoms may not be as severe and may also include
exercise-related problems in the muscles, such as pain
and cramps. The symptoms abate after puberty with
proper treatment. Most cases of GSD IX are linked to
the X chromosome and therefore affect males.



Type X is caused by a defect in the cyclic adenosine
monophosphate-dependent (AMP) kinase enzyme
and presents symptoms similar to GSDs VI and IX.

Diagnosis
Diagnosis usually occurs in infancy or childhood,
although some milder types of GSD go unnoticed well
GALE ENCYCLOPEDIA OF MEDICINE

into adulthood and old age. It is even conceivable that
some of the milder GSDs are never diagnosed.
The four major symptoms that typically lead a
doctor to suspect GSDs are low blood sugar, enlarged
liver, retarded growth, and an abnormal blood biochemistry profile. A definitive diagnosis is obtained by
biopsy of the affected organ or organs. The biopsy
sample is tested for its glycogen content and assayed
for enzyme activity. There are DNA-based techniques
for diagnosing some GSDs from more easily available
samples, such as blood or skin. These DNA techniques
can also be used for prenatal testing.

Treatment
Some GSD types cannot be treated, while others
are relatively easy to control through symptom management. In more severe cases, receiving an organ
transplant is the only option. In the most severe
cases, there are no available treatments and the victim
dies within the first few years of life.
Of the treatable types of GSD, many are treated
by manipulating the diet. The key to managing GSD I
is to maintain consistent levels of blood glucose
through a combination of nocturnal intragastric feeding (usually for infants and children), frequent highcarbohydrate meals during the day, and regular oral
doses of cornstarch (people over age 2). Juvenile and
adult forms of GSD II can be managed somewhat by a
high protein diet, which also helps in cases of GSD III,
GSD VI, and GSD IX. GSD V and GSD VII can also
be managed with a high protein diet and by avoiding
strenuous exercise.
For GSD cases in which dietary therapy is ineffective, organ transplantation may be the only viable
alternative. Liver transplants have been effective in
reversing the symptoms of GSD IV.
Advances in genetic therapy offer hope for effective treatment in the future. This therapy involves
using viruses to deliver a correct form of the gene to
affected cells. Another potential therapy utilizes transgenic animals to produce correct copies of the defective enzyme in their milk. In late 1997, a Dutch
pharmaceutical company, Pharming Health Care
Products, began clinical trials to treat GSD II with
human alpha-glucosidase derived from the milk of
transgenic rabbits. Researchers at Duke University
in North Carolina are also focusing on a treatment
for Pompe’s disease and, aided by Synpac
Pharmaceuticals Limited of the United Kingdom,
plan to begin clinical trials of a recombinant form of
the enzyme in 1998.
1629

Glycogen storage diseases

glycogen constructed in GSD IV is abnormal and
insoluble. As it accumulates in the cells, cell death
leads to organ damage. Infants born with GSD IV
appear normal at birth, but are diagnosed with
enlarged livers and failure to thrive within their first
year. Infants who survive beyond their first birthday
develop cirrhosis of the liver by age 3–5 and die as a
result of chronic liver failure.

Glycosylated hemoglobin test

KEY TERMS
Amniocentesis—A medical test done during pregnancy in which a small sample of the amniotic fluid
is taken from around the fetus. The fluid contains
fetal cells that can be examined for genetic
abnormalities.
Autosomal gene—A gene found on one of the 22
autosomal chromosome pairs; i.e., not on a sex
(X or Y) chromosome.
Chorionic villus sampling—A medical test done
during pregnancy in which a sample of the membrane surrounding the fetus is removed for examination. This examination can reveal genetic fetal
abnormalities.
Glucose—A form of sugar that serves as the body’s
main energy source.
Glycogen—A macromolecule composed mainly of
glucose that serves as the storage form of glucose
that is not immediately needed by the body.
Glycogenolysis—The process of tearing-down a
glycogen molecule to free up glucose.
Glycogenosis—An alternate term for glycogen storage disease. The plural form is glycogenoses.
Gout—A painful condition in which uric acid precipitates from the blood and accumulates in joints
and connective tissues.
Mendelian inheritance—An inheritance pattern for
autosomal gene pairs. The genetic trait displayed
results from one parent’s gene dominating over the
gene inherited from the other parent.
Osteoporosis—A disease in which the bones
become weak and brittle.
Renal disease—Kidney disease.
Transgenic animal—Animals that have had genes
from other species inserted into their genetic code.

Prognosis
People with well-managed, treatable types of
GSD can lead long, relatively normal lives. This goal
is accomplished with the milder types of GSD, such as
Types VI, IX, and X. As the GSD type becomes more
severe, a greater level of vigilance against infections
and other complications is required. Given current
treatment options, complications such as liver disease,
heart failure, and respiratory failure may not be
warded-off indefinitely. Quality of life and life expectancy are substantially decreased.
1630

Prevention
Because GSD is an inherited condition, it is not
preventable. If both parents carry the defective gene,
there is a one-in-four chance that their offspring will
inherit the disorder. Other children may be carriers or
they may miss inheriting the gene altogether.
Through chorionic villi sampling and amniocentesis, the disorder can be detected prior to birth. Some
types of GSD can be detected even before conception
occurs, if both parents are tested for the presence of
the defective gene. Before undergoing such testing, the
prospective parents should meet with a genetic counselor and other professionals in order to make an
informed decision.
Resources
ORGANIZATIONS

Acid Maltase Deficiency Association. PO Box 700248, San
Antonio, TX 78270-0248. (210) 494-6144. <http://
www.amda-pompe.org>.
American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
Association for Glycogen Storage Disease. PO Box 896,
Durant, Iowa 52747-9769. (319) 785-6038.

Julia Barrett

Glycosylated hemoglobin test
Definition
Glycosylated hemoglobin is a test that indicates
how much sugar has been in a person’s blood during
the past two to four months. It is used to monitor the
effectiveness of diabetes treatment.

Purpose
Diabetes is a disease in which a person cannot
effectively use sugar in the blood. Left untreated,
blood sugar levels can be very high. High sugar levels
increase risk of complications, such as damage to eyes,
kidneys, heart, nerves, blood vessels, and other
organs.
A routine blood sugar test reveals how close to
normal a sugar level is at the time of the test. The
glycosylated hemoglobin test reveals how close to normal it has been during the past several months.
GALE ENCYCLOPEDIA OF MEDICINE

Description

KEY TERMS
Diabetes mellitus—A disease in which a person
can’t effectively use sugar in the blood to meet the
needs of the body. It is caused by a lack of the
hormone insulin.

The Diabetes Control and Complications Trial
(DCCT) demonstrated that people with diabetes who
maintained blood glucose (sugar) and total fasting
hemoglobin levels at or close to a normal range
decreased their risk of complications by 50–75%.
Based on results of this study, the American Diabetes
Association (ADA) recommends routine glycosylated
hemoglobin testing to measure long-term control of
blood sugar.

Glucose—The main form of sugar used by the body
for energy.

Glycosylated hemoglobin measures the percentage of hemoglobin bound to glucose. Hemoglobin is
a protein found in every red blood cell. As hemoglobin
and glucose are together in the red blood cell, the
glucose gradually binds to the A1c form of hemoglobin in a process called glycosylation. The amount
bound reflects how much glucose has been in the
blood during the past average 120-day lifespan of
red cells.

In 2004, more convenient fingerstick methods of
the test were being developed. An over-the-counter,
at-home test kit was in the beginning stages of
approval. People with diabetes could stick their own
fingers, draw the blood and send the sample by mail
for results within five to seven days.

Several methods are used to measure the amount
of bound hemoglobin and glucose. They are electrophoresis, chromatography, and immunoassay. All are
based on the separation of hemoglobin bound to glucose from that without glucose.
The ADA recommends glycosylated hemoglobin
be done during a person’s first diabetes evaluation,
again after treatment is begun and sugar levels are
stabilized, then repeated at least semiannually. If the
person does not meet treatment goals or sugar levels
have not stabilized, the test should be repeated
quarterly.
Other names for the test include: Hemoglobin
A1c, Diabetic control index, GHb, glycosylated
hemoglobin, and glycated hemoglobin. The test is
covered by insurance. Results usually are available
the following day.

Preparation
A person does not need to fast before this test. A
healthcare worker ties a tourniquet on the person’s
upper arm, locates a vein in the inner elbow region,
and inserts a needle into the vein. Vacuum action
draws the blood through the needle into an attached
tube. Collection of the sample takes only a few minutes. This test requires 5 mL of blood.
GALE ENCYCLOPEDIA OF MEDICINE

Glycosylated hemoglobin—A test that measures
the amount of hemoglobin bound to glucose. It is
a measure of how much glucose has been in the
blood during the past two to four months.

Aftercare
Discomfort or bruising may occur at the puncture
site, or the person may feel dizzy or faint. Pressure to
the puncture site until bleeding stops reduces bruising.
Warm packs relieve discomfort.

Normal results
Diabetes treatment should achieve glycosylated
hemoglobin levels of less than 7.0%. Normal value
for a non-diabetic person is 4.0–6.0%.
Because laboratories use different methods, results
from different laboratories can not always be compared. The National Glycosylation Standardization
Program gives a certification to laboratories using
tests standardized to those used in the DCCT study.

Abnormal results
Results require interpretation by a physician with
knowledge of the person’s clinical condition, as well as
the test method used. Some methods give false high or
low results if the person has an abnormal hemoglobin,
such as hemoglobin S or F.
Conditions that increase the lifespan of red cells,
such as a splenectomy (removal of the spleen), falsely
increase levels. Conditions that decrease the lifespan,
such as hemolysis (disruption of the red blood cell
membrane), falsely decrease levels.
1631

Glycosylated hemoglobin test

This information helps a physician evaluate how
well a person is responding to diabetes treatment and
to determine how long sugar levels have been high in a
person newly diagnosed with diabetes.

Goiter

Resources
PERIODICALS

‘‘Simple Choice A1c.’’ Diabetes Forecast January
2004: RG7.
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
National Diabetes Information Clearinghouse. 1
Information Way, Bethesda, MD 20892-3560. (800)
860-8747. <http://www.niddk.nih.gov/health/diabetes/
ndic.htm>.

Nancy J. Nordenson
Teresa G. Odle

This woman’s goiter may have been caused by an insufficient
intake of iodine. (Custom Medical Stock Photo. Reproduced by
permission.)

Goiter
Definition
and secrete too much thyroxin. The result–
hyperthyroidism with a goiter. Graves’ disease is
the most common form of this disorder.

Goiter refers to any visible enlargement of the
thyroid gland.

Description
The thyroid gland sits astride the trachea (windpipe) and is shaped like a butterfly. It makes thyroxin,
a hormone that regulates the metabolic activity of the
body, rather like the gas pedal on a car. Too much
thyroxin increases the metabolism, causing weight
loss, temperature elevation, nervousness, and irritability. Too little thyroxin slows the metabolism down,
deepens the voice, causes weight gain and water retention, and retards growth and mental development in
children. Both conditions also alter hair and skin
growth, bowel function, and menstrual flow.
Curiously, the thyroid gland is often enlarged
whether it is making too much hormone, too little, or
sometimes even when it is functioning normally. The
thyroid is controlled by the pituitary gland, which
secretes thyroid stimulating hormone (TSH) in
response to the amount of thyroxin it finds in the
blood. TSH increases the amount of thyroxin secreted
by the thyroid and also causes the thyroid gland
to grow.


Hyperthyroid goiter–If the amount of stimulating
hormone is excessive, the thyroid will both enlarge

1632



Euthyroid goiter–The thyroid is the only organ in the
body to use iodine. If dietary iodine is slightly inadequate, too little thyroxin will be secreted, and the
pituitary will sense the deficiency and produce more
TSH. The thyroid gland will enlarge enough to make
sufficient thyroxin.



Hypothyroid goiter–If dietary iodine is severely
reduced, even an enlarged gland will not be able to
make enough thyroxin. The gland will keep growing
under the influence of TSH, but it may never be able
to make enough thyroxin.

Causes and symptoms
Excess TSH (or similar hormones), cysts, and
tumors will enlarge the thyroid gland. Of these, TSH
enlarges the entire gland while cysts and tumors
enlarge only a part of it.
The only symptom from a goiter is the large
swelling just above the breast bone. Rarely, it may
constrict the trachea (windpipe) or esophagus and
cause difficulty breathing or swallowing. The
rest of the symptoms come from thyroxin or the
lack of it.
GALE ENCYCLOPEDIA OF MEDICINE

Cyst—A liquid-filled structure developing abnormally in the body.
Euthyroid—Having the right amount of thyroxin
stimulation.
Hyperthyroid—Having
stimulation.
Hypothyroid—Having
stimulation.

too

much

thyroxin

too

little

thyroxin

Pituitary gland—The master gland, located in the
middle of the head, that controls most of the other
glandss by secreting stimulating hormones.
Radiotherapy—The use of ionizing radiation,
either as x rays or radioactive isotopes, to treat
disease.
Thyroxin—The hormone secreted by the thyroid
gland.

Euthyroid goiter and hypothyroid goiter are common around the world because many regions have
inadequate dietary iodine, including some places in
the United States. International relief groups are providing iodized salt to many of these populations.
Because mental retardation is a common result of
hypothyroidism in children, this is an extremely important project.
Resources
ORGANIZATIONS

International Council for the Control of Iodine Deficiency
Disorders. 43 Circuit Road, Chester Hill, MA, 02167.
(207) 335-2221. <http://www.tulane.edu/~icec/
icciddhome.htm>.
Micronutrient Initiative (c/o International Development
Research Centre). 250 Albert St., Ottawa, Ontario,
Canada K1G 3H9. (613) 236-6163, ext. 2050. <http://
www.idrc.ca/mi/index.htm>.

J. Ricker Polsdorfer, MD

Diagnosis
The size, shape, and texture of the thyroid gland
help the physician determine the cause. A battery of
blood tests are required to verify the specific thyroid
disease. Functional imaging studies using radioactive
iodine determine how active the gland is and what it
looks like.

Treatment
Goiters of all types will regress with treatment of
the underlying condition. Dietary iodine may be all
that is needed. However, if an iodine deficient thyroid
that has grown in size to accommodate its deficiency is
suddenly supplied an adequate amount of iodine, it
could suddenly make large amounts of thyroxin and
cause a thyroid storm, the equivalent of racing your
car motor at top speed.
Hyperthyroidism can be treated with medications,
therapeutic doses of radioactive iodine, or surgical reduction. Surgery is much less common now than it used to be
because of progress in drugs and radiotherapy.

Prognosis
Although goiters diminish in size, the thyroid may
not return to normal. Sometimes thyroid function
does not return after treatment, but thyroxin is easy
to take as a pill.
GALE ENCYCLOPEDIA OF MEDICINE

Gonadal dysgenesis see Turner syndrome

Gonorrhea
Definition
Gonorrhea is a highly contagious sexually transmitted disease that is caused by the bacterium
Neisseria gonorrhoeae. The mucous membranes of
the genital region may become inflamed without the
development of any other symptoms. When symptoms
occur, they are different in men and women. In men,
gonorrhea usually begins as an infection of the vessel
that carries urine and sperm (urethra). In women, it
will most likely infect the narrow part of the uterus
(cervix). If untreated, gonorrhea can result in serious
medical complications.

Description
Gonorrhea is commonly referred to as ‘‘the clap.’’
The incidence of gonorrhea has steadily declined since
the 1980s, largely due to increased public awareness
campaigns and the risk of contracting other sexually
transmitted diseases, such as AIDS. Still, current estimates range from 400,000 to as many as one million
projected cases of gonorrhea in the United States each
year. These estimates vary due to the private nature of
the disease and the consequent underreporting that
1633

Gonorrhea

Prevention

KEY TERMS

Gonorrhea

can also result in severe damage to the reproductive
system, making an individual unable to conceive a
child (sterile).
Symptoms of gonorrhea in women
As many as 80% of women with gonorrhea show
no symptoms. If present, symptoms may include the
following:

A transmission electron microscopy (TEM) image of Neisseria
gonorrhoeae. (Custom Medical Stock Photo. Reproduced by
permission.)

occurs. The majority of reported cases of gonorrhea
come from public health clinics.
The disease affects people of all ages, races, and
socioeconomic levels, but some individuals are more
at-risk than others. Adolescents and young adults are
the highest risk group, with more than 80% of the
reported cases each year occurring in the 15–29 age
group. Those individuals with multiple sexual partners
and who use no barrier contraception, such as condoms, are most at-risk. Reported rates vary among
racial and ethnic groups.
The risk factors for gonorrhea are not unlike those
for all sexually transmitted diseases. Both men and
women can become infected through a variety of sexual contact behaviors, including oral, anal, or vaginal
intercourse. The disease is transmitted very efficiently.
In fact, women run a 60–90% chance of contracting
the disease after just one sexual encounter with an
infected male. The disease can also be transmitted
from an infected mother to her infant during delivery.

Causes and symptoms
If treated early, gonorrhea can be cured.
Unfortunately, many individuals with gonorrhea, particularly women, will experience no symptoms to alert
them to the possibility that they have contracted
gonorrhea, and therefore, many do not seek treatment. When present, the symptoms and complications
of gonorrhea are primarily limited to the genital, urinary, and gastrointestinal systems and usually begin
between one day and two weeks following infection.
If left untreated, serious complications can result if the
disease spreads to the bloodstream and infects the
brain, heart valves, and joints. Untreated gonorrhea
1634



bleeding between menstrual periods



chronic abdominal pain



painful urination



vaginal discharge, often cloudy and yellow



in the case of oral infection, there may be no symptoms or only a sore throat.



anal infection may cause rectal itching or discharge.

Because women often do not show any symptoms,
complications are more likely to occur as the disease
progresses. The most common complication is pelvic
inflammatory disease (PID). PID can occur in up to
40% of women with gonorrhea and may result in
damage to the fallopian tubes, a pregnancy developing
outside the uterus (ectopic pregnancy), or sterility. If
an infected woman is pregnant, gonorrhea can be
passed on to her newborn through the birth canal
during delivery. These infants may experience eye
infections that could lead to blindness.
Symptoms of gonorrhea in men
Men are more likely to experience the following
symptoms:


thick and cloudy discharge from the penis



burning or pain during urination



more frequent urination



in the case of oral infection, there may be no symptoms or only a sore throat



anal infection may cause rectal itching or discharge

In men, complications can affect the prostate,
testicles, and surrounding glands. Inflammation, tissue death and pus formation (abscesses), and scarring
can occur and result in sterility.

Diagnosis
The diagnosis of gonorrhea can be made at a
public health clinic or a family physician office. First,
the doctor will discuss symptoms and the patient’s
known contact or at-risk behavior. There are three
methods available to test for the presence of
GALE ENCYCLOPEDIA OF MEDICINE

Gram stains are more accurate in the diagnosis of
gonorrhea in men than in women. To perform this
test, a small amount of discharge from the infected
area will be placed on a slide, stained with a special
dye, and examined under a microscope for the presence of the gonococcus bacteria. The advantage to
this test is that results can be obtained very quickly at
the initial visit. Because it requires that the physician
or technician be able to recognize and accurately identify the bacteria simply by looking at it under a microscope, however, this test is only about 70% accurate.
As a result, one of the other methods may also be used
to confirm the diagnosis.
ELISA, or enzyme-linked immunosorbent assay,
has emerged as a rapid and sensitive test for gonorrhea. It is much more sensitive than the gram stain and
is more convenient than the culture test, which
involves the transport and storage of samples. As of
late 1997, several other diagnostic tests were being
researched with the goal of providing a cost-effective
method of screening for a variety of sexually transmitted diseases. One of the most interesting of these is
a home test that can be taken by the patient themselves, allowing for a degree of privacy and
confidentiality.
When a patient suspects exposure to or experiences symptoms of gonorrhea, he or she may see a
public health provider or family practice physician.
Physicians trained in obstetrics or gynecology may
also be involved, particularly if gynecological complications occur. Men who experience complications may
be referred to a urologist. There are also infectious
disease physicians who specialize in the treatment
and research of all infectious diseases, including
those transmitted sexually. All physicians must report
this highly contagious disease to public health officials, and patients are asked to provide the names of
sex partners during the suspected period of infection
so that they can be notified of the risk.

Treatment
Gonorrhea has become more difficult and expensive to treat since the 1970s, due to the increased
GALE ENCYCLOPEDIA OF MEDICINE

resistance of gonorrhea to certain antibiotics. In fact,
according to projections from the Centers for Disease
Control and Prevention, 30% of the strains of gonorrhea were resistant to routine antibiotics in 1994, and
resistance has been increasing steadily. Furthermore,
many patients have both gonorrhea and chlamydial
infections. Therefore, two drug treatment regimens
are common. Medications used to treat gonorrhea
include ceftriaxone, cefixime, spectinomycin, ciprofloxacin, and ofloxacin. Ceftriaxone and doxycycline
or azithromycin are often given simultaneously to
treat possible co-existing chlamydia (in pregnant
women, erythromycin should be substituted for the
aforementioned anti-chlamydial agents). In 2004,
reports said that oral antibiotics were preferred over
intramuscular forms of the drugs. Also, researchers
reported that cefixime had not been available and that
fluoroquinolone had been used by more physicians to
treat gonorrhea. However, fluoroquinolone resistance
was rising among patients with gonorrhea, and in
June 2004 the Centers for Disease Control recommended that clinicians no longer prescribe the drug
as first-line treatment for gonorrhea in men who have
sex with men.
An extremely important consideration is to
make sure that all of the prescribed medication is
taken. If a course of antibiotics is not completed,
the medication will only kill those organisms that
are susceptible to the antibiotic, allowing those that
are resistant to the effects of that particular antibiotic
to multiply and possibly cause a new infection that
will be more difficult to treat. Patients should refrain
from sexual intercourse until treatment is complete
and return for follow-up testing. Any sexual partners
during the time of infection, even if those partners
do not show symptoms, should be notified and
treated when any sexually transmitted disease is
involved.

Alternative treatment
Although there is no known alternative to antibiotics in the treatment of gonorrhea, there are herbs
and minerals that may be used to supplement antibiotic treatment:


Lactobacillus acidophilus or live-culture yogurts are
helpful, while taking antibiotics, to replenish gastrointestinal flora.



The following supplements may be used to improve
the body’s immune function: zinc, multivitamins and
mineral complexes, vitamin C, and garlic (Allium
sativum).
1635

Gonorrhea

Neisseria gonorrhoeae. These include a culture, a
Gram stain, and an ELISA test. Culture of secretions
from the infected area is the preferred method for
gonorrhea screening in patients with or without symptoms. A cotton swab can be used to collect enough
sample for a culture. The sample is incubated for up to
two days, providing enough time for the bacteria to
multiply and be accurately identified. This test is
nearly 100% accurate.

Gonorrhea



Several herbs may reduce some symptoms or help
speed healing: kelp has balanced vitamins and minerals. Calendula (Calendula officinalis), myrrh
(Commiphora molmol), and thuja (Thuja occidentalis)
may help reduce discharge and inflammation when
used as a tea or douche.



Hot baths may also help reduce pain and
inflammation.



A variety of herbs may help with symptoms of the
reproductive and urinary systems.



If a physician approves, fasting, combined with certain juices, may help cleanse the urinary and gastrointestinal systems.



There may be acupressure and acupuncture points
that will help with system cleansing. These exact
pressure points can be provided and treated by an
acupressurist or acupuncturist.

Prognosis
The prognosis for patients with gonorrhea varies
based on how early the disease is detected and treated. If treated early and properly, patients can be
entirely cured of the disease. Up to 40% of female
patients who are not treated early may develop pelvic
inflammatory disease (PID) and the possibility of
resulting sterility. Although the risk of infertility is
higher in women than in men, men may also become
sterile if the urethra becomes inflamed (urethritis)
as a result of an untreated gonorrhea infection.
Following an episode of PID, a woman is six to
10 times more likely, should a pregnancy occur, to
have a pregnancy develop outside the uterus (ectopic
pregnancy), which can result in death. Liver infection
may also occur in untreated women. In approximately 2% of patients with untreated gonorrhea,
the gonococcal infection may spread throughout
the body and can cause fever, arthritis-like joint
pain, and skin lesions.

Prevention
Currently, there is no vaccine for gonorrhea,
but several are under development. The best prevention is to abstain from having sex or to engage
in sex only when in a mutually monogamous relationship in which both partners have been tested
for gonorrhea, AIDS, and other sexually transmitted diseases. The next line of defense is the use
of condoms, which have been shown to be highly
effective in preventing disease (and unwanted pregnancies). To be 100% effective, condoms must be
used properly. A female birth-control device that
1636

KEY TERMS
Cervix—The narrow part or neck of the uterus.
Chlamydia—The most common bacterial sexually transmitted disease in the United States that
often accompanies gonorrhea and is known for
its lack of evident symptoms in the majority of
women.
Ectopic pregnancy—A pregnancy that occurs outside the uterus, such as in the fallopian tubes.
Although the fetus will not survive, in some cases,
ectopic pregnancy can also result in the death of
the mother.
ELISA—Enzyme-linked immunosorbent assay. This
test has been used a screening test for AIDS for
many years and has also been used to detect gonorrhea bacteria.
HIV—Human immunodeficiency virus, the virus
that causes AIDS. The risk of acquiring AIDS is
increased by the presence of gonorrhea or other
sexually transmitted diseases.
Neisseria gonorrhoeae—The bacterium that
causes gonorrhea. It cannot survive for any length
of time outside the human body.
Pelvic inflammatory disease (PID)—An infection
of the upper genital tract that is the most serious
threat to a woman’s ability to reproduce. At least
25% of women who contract the disease, which
can be a complication of gonorrhea, will experience long-term consequences such as infertility or
ectopic pregnancy.
Sexually transmitted diseases (STDs)—A group of
diseases which are transmitted by sexual contact.
In addition to gonorrhea, this groups generally
includes chlamydia, HIV (AIDS), herpes, syphilis,
and genital warts.
Sterile—Unable to conceive a child.
Urethra—The canal leading from the bladder, and
in men, also a path for sperm fluid.
Urethritis—Inflammation of the urethra.

blocks the entry of sperm into the cervix (diaphragm) can also reduce the risk of infection. The
risk of contracting gonorrhea increases with the
number of sexual partners. Any man or woman
who has sexual contact with more than one partner
is advised to be tested regularly for gonorrhea and
other sexually transmitted diseases.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Sparling, P. Fredrick. ‘‘Gonococcal Infections.’’ In Cecil
Textbook of Medicine, edited by Russel L. Cecil, et al.
Philadelphia: W.B. Saunders Company, 2000.
PERIODICALS

‘‘Fluoroquinolone-resistant Gonorrhea on the Rise:
Exposure History is Critical.’’ Emergency Medicine
Alert July 2004: 11–12.
Georgia, Kristen. ‘‘Revised Approach to Gonorrhea
Treatment.’’ Patient Care July 2004: 11.
ORGANIZATIONS

American Foundation for the Prevention of Venereal
Disease, Inc. 799 Broadway, Suite 638, New York, NY
10003. (212) 759-2069.
National Institute of Allergy and Infectious Diseases.
National Institutes of Health, Bethesda, MD 20892.

bloody sputum, difficulty breathing after exertion,
weakness, fatigue, nausea or vomiting, weight loss,
nonspecific chest pain and/or pale skin.

Diagnosis
The clinician will perform a battery of tests to confirm a diagnosis. These tests include a complete blood
count (CBC) to confirm anemia, iron levels to check for
blood loss and blood urea nitrogen (BUN) and creatinine levels to test the kidney function. A urinalysis will
be done to check for damage to the kidneys. A sputum
test will be done to look for specific antibodies. A chest
x ray will be done to assess the amount of fluid in the
lung tissues. A lung needle biopsy and a kidney biopsy
will show immune system deposits. The kidney biopsy
can also show the presence of the harmful antibodies
that attack the lungs and kidneys.

Teresa G. Odle

Treatment

Goodpasture’s syndrome
Definition
An uncommon and life-threatening hypersensitivity disorder believed to be an autoimmune process
related to antibody formation in the body.
Goodpasture’s syndrome is characterized by renal
(kidney) disease and lung hemorrhage.

Description
The disorder is characterized by autoimmune
reaction which deposits of antibodies in the membranes of both the lung and kidneys, causing both
inflammation of kidney (glomerulonephritis) and lung
bleeding. It is typically a disease of young males.

Causes and symptoms
The exact cause is unknown. It is an autoimmune
disorder; that is, the immune system is fighting the body’s
own normal tissues through creating antibodies that
attack the lungs and kidneys. Sometimes the disorder is
triggered by a viral infection, or by the inhalation of
gasoline or other hydrocarbon solvents. An association
also exists between cigarette smoking and the syndrome.
The target antigen of the Goodpasture’s antibodies has
been localized to a protein chain (type IV collagen).
Symptoms include foamy, bloody, or dark
colored urine, decreased urine output, cough with
GALE ENCYCLOPEDIA OF MEDICINE

Treatment is focused on slowing the progression
of the disease. Treatment is most effective when begun
early, before kidney function has deteriorated to a
point where the kidney is permanently damaged, and
dialysis is necessary. Corticosteroids, such as prednisone, or other anti-inflammatory medications may be
used to reduce the immune response. Immune suppressants such as cyclophosphamide or azathioprine
are used aggressively to reduce immune system effects.
A procedure whereby blood plasma, which contains
antibodies, is removed from the body and replaced with
fluids or donated plasma (plasmapheresis) may be performed daily for two or more weeks to remove circulating
antibodies. It is fairly effective in slowing or reversing the
disorder. Dialysis to clean the blood of wastes may be
required if kidney function is poor. A kidney transplant
may be successful, especially if performed after circulating antibodies have been absent for several months.

Prognosis
The probable outcome is variable. Most cases
progress to severe renal failure and end-stage renal
disease within months. Early diagnosis and treatment
makes the probable outcome more favorable.

Prevention
No known prevention of Goodpasture’s syndrome
exists. People should avoid glue sniffing and the siphoning
gasoline. Stopping smoking, if a family history of renal
failure exists, may prevent some cases. Early diagnosis
and treatment may slow progression of the disorder.
1637

Goodpasture’s syndrome

Resources

Gout

KEY TERMS
Antibody—A protein molecule produced by the
immune system in response to a protein that is not
recognized as belonging in the body.
Antigen—Any substance that, as a result of coming
in contact with appropriate cells,induces a state of
sensitivity and/or immune responsiveness after a
period of time and that reacts in a demonstrable
way with antibodies.
Autoimmune disorder—An abnormality within the
body whereby the immune system incorrectly
attacks the body’s normal tissues, thereby causing
disease or organ dysfunction.
Blood urea nitrogen (BUN)—A test used to measure the blood level of urea nitrogen, a waste that is
normally filtered from the kidneys.
Creatinine—A test used to measure the blood level
of creatinine, a waste product filtered out of the
blood by the kidneys. Higher than usual levels of
this substance may indicate kidney disease.
Glomerulus (glomeruli)—A small tuft of blood
capillaries in the kidney, responsible for filtering
out waste products.

Resources
BOOKS

Tierney, Lawrence, et. al. Current Medical Diagnosis and
Treatment. Los Altos: Lange Medical Publications,
2001.
ORGANIZATIONS

American Kidney Fund. 6110 Executive Boulevard, Suite
1010, Rockville, MD 20852. (800) 638-8299. <http://
www.akfinc.org>.
National Kidney Foundation. 30 East 33rd Street, New
York, NY 10016. (800) 622-9010. <http://
www.kidney.org>.

Kim A. Sharp, M.Ln.

Gout
Definition
Gout is a form of acute arthritis that causes severe
pain and swelling in the joints. It most commonly
affects the big toe, but may also affect the heel,
1638

ankle, hand, wrist, or elbow. It affects the spine often
enough to be a factor in back pain. Gout usually
comes on suddenly, goes away after 5–10 days, and
can keep recurring. Gout is different from other forms
of arthritis because it occurs when there are high levels
of uric acid circulating in the blood, which can cause
urate crystals to settle in the tissues of the joints.

Description
Uric acid, which is found naturally in the blood
stream, is formed as the body breaks down waste
products, mainly those containing purine, a substance
that is produced by the body and is also found in high
concentrations in some foods, including brains, liver,
sardines, anchovies, and dried peas and beans.
Normally, the kidneys filter uric acid out of the
blood and excrete it in the urine. Sometimes, however,
the body produces too much uric acid or the kidneys
aren’t efficient enough at filtering it from the blood,
and it builds up in the blood stream, a condition
known as hyperuricemia. A person’s susceptibility to
gout may increase because of the inheritance of certain
genes or from being overweight and eating a rich diet.
In some cases, another disease (such as lymphoma,
leukemia, or hemolytic anemia) may be the underlying
cause of the uric acid buildup that results in gout. An
additional factor is occupational or environmental; it
is now known that chronic exposure to high levels of
lead decreases the body’s excretion of urates, allowing
uric acid to accumulate in the blood.
Hyperuricemia doesn’t always cause gout. Over
the course of years, however, sharp urate crystals build
up in the synovial fluid of the joints. Often, some
precipitating event, such as an infection, surgery, the
stress of hospitalization, a stubbed toe, or even a heavy
drinking binge can cause inflammation. White blood
cells, mistaking the urate crystals for a foreign invader,
flood into the joint and surround the crystals, causing
inflammation—in other words, the redness, swelling,
and pain that are the hallmarks of a gout attack.

Causes and symptoms
As a result of high levels of uric acid in the blood,
needle-like urate crystals gradually accumulate in the
joints. Urate crystals may be present in the joint for a
long time without causing symptoms. Infection, injury
to the joint, surgery, drinking too much, or eating the
wrong kinds of foods may suddenly bring on the
symptoms, which include pain, tenderness, redness,
warmth, and swelling of the joint. In many cases, the
gout attack begins in the middle of the night. The pain
is often so excruciating that the sufferer cannot bear
GALE ENCYCLOPEDIA OF MEDICINE

Gout affects an estimated one million
Americans; according to the National Institutes of
Health, it accounts for about 5% of all cases of
arthritis. It occurs more often in men than in
women; the sex ratio is about 4:1. Uric-acid levels
tend to increase in men at puberty, and, because it
takes 20 years of hyperuricemia to cause gout symptoms, men commonly develop gout in their late 30s
or early 40s. Women more typically develop gout
later in life, starting in their 60s. According to some
medical experts, estrogen protects against hyperuricemia, and when estrogen levels fall during menopause, urate crystals can begin to build up in the
joints. Excess body weight, regular excessive alcohol
intake, the use of blood pressure medications called
diuretics, and high levels of certain fatty substances
in the blood (serum triglycerides) associated with an
increased risk of heart disease can all increase a
person’s risk of developing gout.
Gout appears to be on the increase in the
American population. According to a study published in November 2002, there was a twofold
increase in the incidence of gout over the 20 years
between 1977 and 1997. It is not yet known whether
this increase is the result of improved diagnosis or
whether it is associated with risk factors that have
not yet been identified.

Diagnosis
Usually, physicians can diagnose gout based on
the physical examination and medical history (the
patient’s description of symptoms and other information). Doctors can also administer a test that
measures the level of uric acid in the blood. While
normal uric acid levels don’t necessarily rule out gout
and high levels don’t confirm it, the presence of
hyperuricemia increases the likelihood of gout. The
development of a tophus can confirm the diagnosis
of gout. The most definitive way to diagnose gout is
GALE ENCYCLOPEDIA OF MEDICINE

Gout

weight on the joint or tolerate the pressure of bedcovers. The inflamed skin over the joint may be red,
shiny, and dry, and the inflammation may be accompanied by a mild fever. These symptoms may go away
in about a week and disappear for months or years at a
time. However, over the course of time, attacks of gout
recur more and more frequently, last longer, and affect
more joints. Eventually, stone-like deposits known as
tophi may build up in the joints, ligaments, and tendons, leading to permanent joint deformity and
decreased motion. (In addition to causing the tophi
associated with gout, hyperuricemia can also cause
kidney stones, also called renal calculi or uroliths.)

Uric acid
crystals

Gout, a form of acute arthritis, most commonly occurs in the
big toe. It is caused by high levels of uric acid in the blood, in
which urate crystals settle in the tissues of the joints and
produce severe pain and swelling. (Illustration by Electronic
Illustrators Group.)

to take a sample of fluid from the joint and test it for
urate crystals.

Treatment
The goals of treatment for gout consist of alleviating pain, avoiding severe attacks in the future, and
preventing long-term joint damage. In addition to
taking pain medications as prescribed by their doctors,
people having gout attacks are encouraged to rest and
to increase the amount of fluids that they drink.
Acute attacks of gout can be treated with nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs)
such as naproxen sodium (Aleve), ibuprofen (Advil),
or indomethacin (Indocin). In some cases, these drugs
can aggravate a peptic ulcer or existing kidney disease
and cannot be used. Doctors sometimes also use colchicine (Colbenemid), especially in cases where nonsteroidal anti-inflammatory drugs cannot be used.
Colchicine may cause diarrhea, which tends to go
away once the patient stops taking it. Corticosteroids
such as prednisone (Deltasone) and adrenocorticotropic hormone (Acthar) may be given orally or may be
injected directly into the joint for a more concentrated
effect. While all of these drugs have the potential to
cause side effects, they are used for only about 48
hours and are not likely to cause major problems.
However, aspirin and closely related drugs (salicylates)
should be avoided because they can ultimately worsen
gout.
Once an acute attack has been successfully treated, doctors try to prevent future attacks of gout and
1639

Gout

long-term joint damage by lowering uric acid levels in
the blood. There are two types of drugs for correcting
hyperuricemia. Such uricosuric drugs as probenecid
(Benemid) and sulfinpyrazone (Anturane) lower the
levels of urate in the blood by increasing its removal
from the body (excretion) through the urine. These
drugs may promote the formation of kidney stones,
however, and they may not work for all patients,
especially those with kidney disease. Allopurinol
(Zyloprim), a type of drug called a xanthine-oxidase
inhibitor, blocks the production of urate in the body,
and can dissolve kidney stones as well as treating gout.
The potential side effects of allopurinol include rash, a
skin condition known as dermatitis, and liver dysfunction. In 2004, the FDA was seeking trial data on a new
drug called oxypurinol (Oxyprim) for treating chronic
gout. These medications may have to be taken for life
to prevent further gout attacks.
New quality of care indicators were released in
2004 to improve care for patients with gout. The aim
of the guidelines was to prevent repeat gout attacks
and to reduce medication errors associated with intravenous colchicine in hospitals.

Alternative treatment
Alternative approaches to gout focus on correcting hyperuricemia by encouraging weigt loss and limiting the intake of alcohol and purine-rich foods. In
addition, consuming garlic (Allium sativum) has been
recommended to help prevent gout. Increasing fluid
intake, especially by drinking water, is also recommended. During an acute attack, contrast hydrotherapy (alternating three-minute hot compresses with
30–second cold compresses) can help dissolve the
crystals and resolve the pain faster.

Prognosis
Gout cannot be cured but usually it can be managed successfully. As tophi dissolve, joint mobility
generally improves. (In some cases, however, medicines alone do not dissolve the tophi and they must
be removed surgically.) Lowering uric acid in the
blood also helps to prevent or improve the kidney
problems that may accompany gout.

Prevention
For centuries, gout has been known as a ‘‘rich
man’s disease’’ or a disease caused by overindulgence
in food and drink. While this view is perhaps a little
overstated and oversimplified, lifestyle factors clearly
influence a person’s risk of developing gout. Since
1640

KEY TERMS
Allopurinol—A drug that corrects hyperuricemia
by inhibiting urate production.
Colchicine—A drug used to treat painful flare-ups
of gout.
Corticosteroids—Medications related to a natural
body hormone called hydrocortisone, which are
used to treat inflammation.
Hyperuricemia—High levels of a waste product
called uric acid in the blood.
Probenecid—A drug that corrects hyperuricemia
by increasing the urinary excretion of urate.
Purine—A substance found in foods that is broken
down into urate and may contribute to hyperuricemia and gout.
Sulfinpyrazone—A drug that corrects hyperuricemia by increasing the urinary excretion of urate.
Synovial fluid—Fluid surrounding the joints which
acts as a lubricant, reducing the friction between
the joints.
Tophus (plural, tophi)—A chalky deposit of a uric
acid compound found in gout. Tophi occur most
frequently around joints and in the external ear.
Urate crystals—Crystals formed by high levels of
uric acid in the blood.

obesity and excessive alcohol intake are associated
with hyperuricemia and gout, losing weight and limiting alcohol intake can help ward off gout. Dehydration
may also promote the formation of urate crystals, so
people taking diuretics or ‘‘water pills’’ may be better
off switching to another type of blood pressure medication. Everyone should be sure to drink at least six to
eight glasses of water each day. Since purine is broken
down in the body into urate, it may also be helpful to
avoid foods high in purine, such as organ meats, sardines, anchovies, red meat, gravies, beans, beer, and
wine. A 2004 study revealed that eating more low-fat
dairy products could reduce risk of developing gout.
Resources
BOOKS

Parker, James N., M.D., and Philip M. Parker, Ph. D. The
2002 Official Patient’s Sourcebook on Gout. San Diego,
CA: ICON Health Publications, 2002.
PERIODICALS

Arromdee, E., C. J. Michet, C. S. Crowson, et al.
‘‘Epidemiology of Gout: Is the Incidence Rising?’’
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

Arthritis Foundation.1300 W. Peachtree St., Atlanta, GA
30309. (800) 283-7800. <http://www.arthritis.org>.
National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS). National Institutes of Health
(NIH), 1 AMS Circle, Bethesda, MD 20892-3675.
<www.niams.nih/gov>.
OTHER

National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS). Questions and Answers About Gout.
Bethesda, MD: NIAMS, 2002. NIH Publication No.
02-5027. <www.niams.nih.gov/hi/topics/gout/gout/
htm>.

Robert Scott Dinsmoor
Rebecca J. Frey, PhD
Teresa G. Odle

Purpose
Gout is a disease in which uric acid, a waste product that normally passes out of the body in urine,
collects and forms crystals in the joints and the kidneys. When uric acid crystals build up in the joints, the
tissue around the joint becomes inflamed, and nerve
endings in the area become irritated, causing extreme
pain. Uric acid crystals in the kidneys can lead to
kidney stones and eventually to kidney failure.
The symptoms of gout–severe pain, usually in the
hand or foot (often at the base of the big toe), but
sometimes in the elbow or knee–should be reported to
a health care professional. If not treated, gout can lead
to high blood presssure, deformed joints, and even
death from kidney failure. Fortunately, the condition
is easily treated. For patients who have just had their
first attack, physicians may prescribe only medicine to
reduce the pain and inflammatin, such as nonsteroidal
anti-inflammatory drugs, corticosteroids, or colchicine.
Patients may also be advised to change their eating
and drinking habits, avoiding organ meats and other
protein-rich foods, cutting out alcoholic beverages,
and drinking more water. Some people never have
another gout attack after the first. For those who do,
physicians may prescribe additional drugs that either
help the body get rid of uric acid or reduce the amount
of uric acid the body produces. These drugs will not
relieve gout attacks that already have started, but will
help prevent attacks when taken regularly.

Description
Three main types of drugs are used in treating
gout. Colchicine helps relieve the symptoms of gout
by reducing inflammation. Allopurinol (Lopurin,
Zyloprim) reduces the amount of uric acid produced
in the body. Probenecid (Benemid, Probalan) and sulfinpyrazone (Anturane) help the body get rid of excess
uric acid. Physicians may recommend that patients
take more than one type of gout drug at the same
time. Some of these medicines may also be prescribed
for other medical conditions that are caused by too
much uric acid in the body.

Recommended dosage

Gout drugs
Definition
Gout drugs are medicines that prevent or relieve
the symptoms of gout, a disease that affects the joints
and kidneys.
GALE ENCYCLOPEDIA OF MEDICINE

The recommended dosage depends on the type of
gout drug. Check with the physician who prescribed
the drug or the pharmacist who filled the prescription
for the correct dosage.
Always take gout drugs exactly as directed. Never
take larger or more frequent doses than recommended. Patients who are told to take more than one
1641

Gout drugs

Journal of Rheumatology 29 (November 2002):
2403–2406.
Coghill, Kim. ‘‘FDA Panel Discusses Endpoints for
Approval of Gout Products.’’ Bioworld Today
(June 3, 2004).
‘‘Dairy-rich Diet May Help Prevent Gout.’’ Tufts University
Health & Nutrition Letter (June 2004): 2.
Hsu, C. Y., T. T. Shih, K. M. Huang, et al. ‘‘Tophaceous
Gout of the Spine: MR Imaging Features.’’ Clinical
Radiology 57 (October 2002): 919–925.
Lin, J. L., D. T. Tan, H. H. Ho, and C. C. Yu.
‘‘Environmental Lead Exposure and Urate Excretion in
the General Population.’’ American Journal of Medicine
113 (November 2002): 563–568.
MacReady, Norma. ‘‘New Gout Quality-of-care Standards
Take Aim at Medication-related Errors.’’ Internal
Medicine News (June 1, 2004): 18.
Perez-Ruiz, F., M. Calabozo, G. G. Erauskin, et al. ‘‘Renal
Underexcretion of Uric Acid is Present in Patients with
Apparent High Urinary Uric Acid Output.’’ Arthritis
and Rheumatism 47 (December 15, 2002): 610–613.
Raj, J. M., S. Sudhakar, K. Sems, and R. W. Carlson.
‘‘Arthritis in the Intensive Care Unit.’’ Critical Care
Clinics 18 (October 2002): 767–780.
Shekarriz, B., and M. L. Stoller. ‘‘Uric Acid Nephrolithiasis:
Current Concepts and Controversies.’’ Journal of
Urology 168, no. 4, Part 1 (October 2002): 1307–1314.

Gout drugs

gout drug should carefully follow the physician’s
directions for taking all medicines.
Gout drugs such as allopurinol, probenecid, and
sulfinpyrazone must be taken regularly to prevent
gout attacks. The medicine may take some time to
begin working, so gout attacks may continuee for
awhile after starting to take the drug. Continuing to
take the drug is important, even if it does not seem to
be working t first.
Colchicine may be taken regularly in low doses to
help prevent gout attacks or in high doses for only a
few hours at a time to relieve an attack. The chance of
serious side effects is greater when this medicine is
taken in high doses for short periods.

Precautions
Seeing a physician regularly while taking gout
drugs is important. The physician will check to make
sure the medicine is working as it should and will
watch for unwanted side effects. Blood tests may be
ordered to help the physician monitor how well the
drug is working.
Drinking alcohol, including beer and wine, may
increase the amount of uric acid in the body and may
interfere with the effects of gout medicine. People with
gout (or other conditions that result from excess uric
acid) may need to limit the amount of alcohol they
drink or stop drinking alcohol altogether.
Some people feel drowsy or less alert when taking
gout drugs. Anyone who takes this type of medicine
should not drive, use machines or do anything else that
might be dangerous until they have found out how the
drugs affect them.
Some gout drugs may change the results of certain
medical tests. Before having medical tests, anyone
taking this medicine should alert the health care professional in charge.
Older people may be especially sensitive to the
effects of colchicine. The drug may also stay in their
bodies longer than it does in younger people. Both the
increased sensitivity to the drug and the longer time
for the drug to leave the body may increase the chance
of side effects.
Special conditions
People who have certain medical conditions or
who are taking certain other medicines can have problems if they take gout drugs. Before taking these
drugs, be sure to let the physician know about any of
these conditions:
1642

ALLERGIES. Anyone who has ever had unusual
reactions to gout drugs or to medicines used to relieve
pain or inflammation should let his or her physician
know before taking gout drugs. The physician should
also be told about any allergies to foods, dyes, preservatives, or other substances.
DIABETES. Some gout drugs may cause false
results on certain urine sugar tests, but not on others.
Diabetic patients who take gout drugs should check
with their physicians to find out if their medicine will
affect the results of their urine sugar tests.
PREGNANCY. The effects of taking gout drugs during pregnancy are not fully understood. Women who
are pregnant or who may become pregnant should
check with their physicians before using gout drugs.
BREASTFEEDING. Gout drugs may pass into breast
milk. Women who are taking this medicine and want
to breastfeed their babies should check with their
physicians.
OTHER MEDICAL CONDITIONS. Gout drugs may
cause problems for people with certain medical conditions. For example, the risk of severe allergic reactions
or other serious side effects is greater when people with
these medical conditions take certain gout drugs:


congestive heart disease



high blood pressure



blood disease



diabetes



kidney disease or kidney stones



cancer being treated with drugs or radiation



stomach or intestinal problems, including stomach
ulcer (now or in the past)

Before using gout drugs, people with any of medical problems listed above should make sure their
physicians are aware of their conditions.
USE OF CERTAIN MEDICINES. Taking gout drugs
with certain other drugs may affect the way the drugs
work or may increase the chance of side effects.

Side effects
A skin rash that develops during treatment with
gout drugs may be a sign of a serious and possibly lifethreatening reaction. If any of these symptoms occur,
stop taking the medicine and check with a physician
immediately:


skin rash, itching, or hives



scaly or peeling skin
GALE ENCYCLOPEDIA OF MEDICINE

chills, fever, sore throat, nausea and vomiting, yellow
skin or eyes, joint pain, muscle aches or pains–
especially if these symptoms occur at the same time
or shortly after a skin rash

Patients taking colchicine should stop taking it
immediately if they have diarrhea, stomach pain, nausea, or vomiting. If these symptoms continue for
3 hours or more after the medicine is stopped, check
with a physician.
Other side effects of may also need medical attention. If any of the following symptoms occur while
taking gout drugs, check with the physician who
prescribed the medicine as soon as possible:


pain in the side or lower back



painful urination



blood in the urine

Less serious side effects, such as headache, loss of
appetite, and joint pain and inflammation usually go
away as the body adjusts to the drug and do not need
medical treatment.
Other side effects may occur. Anyone who has
unusual symptoms while taking gout difficult to interpret. Even so, each individual cell in the body carries
thousands of genes coding for proteins, with some
estimates as high as 150,000 genes. For gene therapy
to advance to its full potential, scientists must discover
the biological role of each of these individual genes
and where the base pairs that make them up are
located on DNA.
To address this issue, the National Institutes of
Health initiated the Human Genome Project in 1990.
Led by James D. Watson (one of the co-discoverers of
the chemical makeup of DNA) the project’s 15-year
goal is to map the entire human genome (a combination of the words gene and chromosomes). A genome
map would clearly identify the location of all genes as
well as the more than three billion base pairs that make
them up. With a precise knowledge of gene locations
and functions, scientists may one day be able to conquer or control diseases that have plagued humanity
for centuries.
Scientists participating in the Human Genome
Project have identified an average of one new gene a
day, but many expect this rate of discovery to increase.
By the year 2005, their goal is to determine the exact
location of all the genes on human DNA and the exact
sequence of the base pairs that make them up. Some of
the genes identified through this project include a gene
that predisposes people to obesity, one associated with
programmed cell death (apoptosis), a gene that guides
HIV viral reproduction, and the genes of inherited
GALE ENCYCLOPEDIA OF MEDICINE

disorders like Huntington’s disease, Lou Gehrig’s disease, and some colon and breast cancers. In February
of 2001, scientists published a rought draft of the
complete human genome. With fewer than the anticipated number of genes found, between 30,000–40,000,
the consequences of this announcement are enormous.
Scientists caution however, that the initial publication
is only a draft of the human genome and much more
work is still ahead for the completion of the project. As
the human genome is completed, there will be more
information available for gene therapy research and
implementation.

The future of gene therapy
Gene therapy seems elegantly simple in its concept: supply the human body with a gene that can
correct a biological malfunction that causes a disease. However, there are many obstacles and some
distinct questions concerning the viability of gene
therapy. For example, viral vectors must be carefully
controlled lest they infect the patient with a viral
disease. Some vectors, like retroviruses, can also
enter cells functioning properly and interfere with
the natural biological processes, possibly leading to
other diseases. Other viral vectors, like the adenoviruses, are often recognized and destroyed by the
immune system so their therapeutic effects are shortlived. Maintaining gene expression so it performs its
role properly after vector delivery is difficult. As a
result, some therapies need to be repeated often to
provide long-lasting benefits.
One of the most pressing issues, however, is gene
regulation. Genes work in concert to regulate their
functioning. In other words, several genes may play a
part in turning other genes on and off. For example,
certain genes work together to stimulate cell division
and growth, but if these are not
Nancy Ross-Flanigan

Gouty arthritis see Gout

Graft-vs.-host disease
Definition
Graft-vs.-host disease is an immune attack on the
recipient by cells from a donor.
1643

Graft-vs.-host disease



Graft-vs.-host disease

Description
The main problem with transplanting organs and
tissues is that the recipient host does not recognize the
new tissue as its own. Instead, it attacks it as foreign in
the same way it attacks germs, to destroy it.
If immunogenic cells from the donor are transplanted along with the organ or tissue, they will attack
the host, causing graft vs. host disease.
The only transplanted tissues that house enough
immune cells to cause graft vs. host disease are the
blood and the bone marrow. Blood transfusions are
used every day in hospitals for many reasons. Bone
marrow transplants are used to replace blood forming
cells and immune cells. This is necessary for patients
whose cancer treatment has destroyed their own bone
marrow. Because bone marrow cells are among the
most sensitive to radiation and chemotherapy, it often
must be destroyed along with the cancer. This is true
primarily of leukemias, but some other cancers have
also been treated this way.

Causes and symptoms
Even if the donor and recipient are well matched,
graft-vs.-host disease can still occur. There are many
different elements involved in generating immune
reactions, and each person is different, unless they
are identical twins. Testing can often find donors
who match all the major elements, but there are
many minor ones that will always be different. How
good a match is found also depends upon the urgency
of the need and some good luck.
Blood transfusion graft-vs.-host disease affects
mostly the blood. Blood cells perform three functions:
carrying oxygen, fighting infections, and clotting. All
of these cell types are decreased in a transfusion graftvs.-host reaction, leading to anemia (lack of red blood
cells in the blood), a decrease in resistance to infections, and an increase in bleeding. The reaction occurs
between four to 30 days after the transfusion.
The tissues most affected by bone marrow graftvs.-host disease are the skin, the liver, and the intestines. One form or the other occurs in close to half of
the patients who receive bone marrow transplants.
Bone marrow graft-vs.-host disease comes in an
acute and a chronic form. The acute form appears
within two months of the transplant; the chronic
form usually appears within three months. The acute
disease produces a skin rash, liver abnormalities, and
diarrhea that can be bloody. The skin rash is primarily
a patchy thickening of the skin. Chronic disease can
produce a similar skin rash, a tightening or an
1644

inflammation of the skin, lesions in the mouth, drying
of the eyes and mouth, hair loss, liver damage, lung
damage, and indigestion. The symptoms are similar to
an autoimmune disease called scleroderma.
Both forms of graft-vs.-host disease bring with
them an increased risk of infections, either because of
the process itself or its treatment with cortisone-like
drugs and immunosuppressives. Patients can die of
liver failure, infection, or other severe disturbances of
their system.

Treatment
Both the acute and the chronic disease are treated
with cortisone-like drugs, immunosuppressive agents
like cyclosporine, or with antibiotics and immune chemicals from donated blood (gamma globulin).
Infection with one particular virus, called cytomegalovirus (CMV) is so likely a complication that some
experts recommend treating it ahead of time.

Prognosis
Children with acute leukemias have greatly benefited from the treatment made possible by bone marrow transplantation. Survival rates have climbed by
15–50%. It is an interesting observation that patients
who develop graft-vs.-host disease are less likely
to have a recurrence of the leukemia that was being
treated. This phenomenon is called graftvs.-leukemia.
Bone marrow transplant patients who do not have
a graft-vs.-host reaction gradually return to normal
immune function in a year. A graft-vs.-host reaction
may prolong the diminished immune capacity indefinitely, requiring supplemental treatment with immunoglobulins (gamma globulin).
Somehow the grafted cells develop a tolerance to
their new home after six to 12 months, and the medications can be gradually withdrawn. Graft-vs.-host
disease is not the only complication of blood transfusion or bone marrow transplantation. Host-vs.-graft
or rejection is also common and may require a repeat
transplant with another donor organ. Infections are a
constant threat in bone marrow transplant because of
the disease being treated, the prior radiation or
chemotherapy and the medications used to treat the
transplant.

Prevention
For recipients of blood transfusions who are
especially likely to have graft-vs.-host reactions, the
GALE ENCYCLOPEDIA OF MEDICINE

Anemia—Too few red blood cells, or too little
hemoglobin in them.
Immunoglobulin—Chemicals in the blood that
defend against infections.
Immunosuppressive—A chemical which suppresses an immune response.
Inflammation—The body’s immune reaction to
presumed foreign substances like germs.
Inflammation is characterized by increased blood
supply and activation of defense mechanisms. It
produces redness, swelling, heat, and pain.
Lesion—Localized disease or damage.
Scleroderma—Progressive disease of the connective tissue of the skin and internal organs.

red blood cells can safely be irradiated (using x rays)
to kill all the immune cells. The red blood cells are
less sensitive to radiation and are not harmed by this
treatment.
Much current research is directed towards solving the problem of graft-vs.-host disease. There are
efforts to remove the immunogenic cells from the
donor tissue, and there are also attempts to extract
and purify bone marrow cells from the patient before
treating the cancer. These cells are then given back to
the patient after treatment has destroyed all that
were left behind.
Resources
BOOKS

Armitage, James O. ‘‘Bone Marrow Transplantation.’’
In Harrison’s Principles of Internal Medicine, edited
by Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Grafts and grafting see Bone grafting;
Coronary artery bypass graft surgery;
Graft-vs.-host disease; Skin grafting

Granuloma inguinale
Definition
Granuloma inguinale is a sexually transmitted
infection that affects the skin and mucous membranes
of the anal and genital areas. Its name is derived from
granuloma, a medical term for a mass or growth of
granulation tissue, and inguinale, a Latin word that
means located in the groin. Granulation tissue is tissue
formed during wound healing that is rich in blood
capillaries and has a rough or lumpy surface.

Description
Granuloma inguinale is a chronic infection with
frequent relapses caused by a rod-shaped bacterium. It
occurs worldwide but is most common in tropical or
subtropical countries, where it is associated with poverty and poor hygiene. As many as 20% of male
patients with sexually transmitted diseases (STDs) in
tropical countries have granuloma inguinale. The disease is less common in the United States, with fewer
than 100 reported cases per year. Most patients are
between the ages of 20 and 40 years, with a 2:1 maleto-female ratio.
Although granuloma inguinale is relatively
uncommon in the United States in comparison with
other STDs, it is still a significant public health problem. It can be acquired through casual sexual contacts when traveling abroad. Moreover, patients with
granuloma inguinale are vulnerable to superinfection
(infection by other disease agents) with other STDs,
especially syphilis. Patients with granuloma inguinale
are also a high-risk group for Acquired Immune
Deficiency Syndrome (AIDS) transmission, because
the disease causes open genital ulcers that can be easily
invaded by the AIDS virus.
Granuloma inguinale is spread primarily through
heterosexual and male homosexual contact; however,
its occurrence in children and sexually inactive adults
indicates that it may also be spread by contact with
human feces. Granuloma inguinale is not highly contagious; however, persons with weakened immune systems are at greater risk of infection.

Causes and symptoms

Granulocytopenia see Neutropenia

Granuloma inguinale, which is sometimes called
donovanosis, is caused by Calymmatobacterium granulomatis, a rod-shaped bacterium formerly called
Donovania granulomatis. The bacterium has an incubation period ranging from eight days to 12 weeks,

GALE ENCYCLOPEDIA OF MEDICINE

1645

Granular conjunctivitis see Trachoma
Granulocytic ehrlichiosis see Ehrlichiosis

Granuloma inguinale

KEY TERMS

Granuloma inguinale

with an average of two to four weeks. The disease has a
slow and gradual onset, beginning with an inconspicuous pimple or lumpy eruption on the skin. In 90% of
patients, the initial sign of infection is in the genital
region, but a minority of patients will develop the sore
in their mouth or anal area if their sexual contact
involved those parts of the body. Many patients do
not notice the sore because it is small and not usually
painful. In some women, the first symptom of granuloma inguinale is bleeding from the genitals.
The initial pimple or sore is typically followed by
three stages of disease. In the first stage, the patient
develops a mass of pink or dull red granulation tissue
in the area around the anus. In the second stage, the
bacteria erode the skin to form shallow, foul-smelling
ulcers which spread from the genital and anal areas to
the thighs and lower abdomen. The edges of the ulcers
are marked by granulation tissue. In the third stage,
the ulcerated areas form deep masses of keloid or scar
tissue that may spread slowly for many years.
Patients with long-term infections are at risk for
serious complications. The ulcers in second-stage
granuloma inguinale often become superinfected
with syphilis or other STD organisms. Superinfected
ulcers become painful to touch, filled with pus and
dead tissue, and are much more difficult to treat.
There may be sizable areas of tissue destruction in
superinfected patients. In addition, the scar tissue produced by third-stage infection can grow until it closes
off parts of the patient’s urinary tract. It is also associated with a higher risk of genital cancer.

Diagnosis
The most important aspect of diagnosis is distinguishing between granuloma inguinale and other
STDs, particularly since many patients will be infected
with more than one STD. Public health officials
recommend that patients tested for granuloma inguinale be given a blood test for syphilis as well. In addition, the doctor will need to distinguish between
granuloma inguinale and certain types of skin cancer,
amebiasis, fungal infections, and other bacterial
ulcers. The most significant distinguishing characteristic of granuloma inguinale is the skin ulcer, which is
larger than in most other diseases, painless, irregular
in shape, and likely to bleed when touched.
The diagnosis of granuloma inguinale is made by
finding Donovan bodies in samples of the patient’s
skin tissue. Donovan bodies are oval rod-shaped
organisms that appear inside infected tissue cells
under a microscope. The doctor obtains a tissue sample either by cutting a piece of tissue from the edge of
1646

KEY TERMS
Donovan bodies—Rod-shaped oval organisms
found in tissue samples from patients with granuloma inguinale. Donovan bodies appear deep purple when stained with Wright’s stain.
Granulation tissue—A kind of tissue formed during
wound healing, with a rough or irregular surface
and a rich supply of blood capillaries.
Granuloma—An inflammatory swelling or growth
composed of granulation tissue, as in granuloma
inguinale.
Keloid—An unusual or abnormal growth of scar
tissue, as in the third stage of granuloma inguinale.
Punch biopsy—A method of obtaining skin samples
under local anesthesia using a surgical skin punch.
Superinfection—A condition in which a patient
with a contagious disease acquires a second infection, as when a patient with granuloma inguinale is
also infected with syphilis.
Wright’s stain—A chemical used to stain tissue
samples for laboratory analysis.

an skin ulcer with a scalpel or by taking a punch
biopsy. To make a punch biopsy, the doctor will inject
a local anesthetic into an ulcerated area and remove a
piece of skin about 1/16 of an inch in size with a
surgical skin punch. The tissue sample is then airdried and stained with Wright’s stain, a chemical that
will cause the Donovan bodies to show up as dark
purple safety pin-shaped objects inside lighter-staining
capsules.

Treatment
Granuloma inguinale is treated with oral antibiotics. Three weeks of treatment with erythromycin, streptomycin, or tetracycline, or 12 weeks of treatment with
ampicillin are standard forms of therapy. Although the
skin ulcers will start to show signs of healing in about a
week, the patient must take the full course of medication to minimize the possibility of relapse.

Prognosis
Most patients with granuloma inguinale recover
completely, although superinfected ulcers may require
lengthy courses of medication. Early treatment prevents the complications associated with second- and
third-stage infection.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention of granuloma inguinale has three
important aspects:


Avoidance of casual sexual contacts, particularly
among homosexual males, in countries with high
rates of the disease



Tracing and examination of an infected person’s
recent sexual contacts



Monitoring the patient’s ulcers or scar tissue for
signs of reinfection for a period of six months after
antibiotic treatment

Resources
BOOKS

Chambers, Henry F. ‘‘Infectious Diseases: Bacterial &
Chlamydial.’’ In Current Medical Diagnosis and
Treatment, 1998. edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Granulomatous ileitis see Crohn’s disease
Graves’ disease see Hyperthyroidism
Greenfield filter see Vena cava
Grippe see Influenza
Group A streptococcus infection see
Streptococcal infections
Group B streptococcus infection see
Streptococcal infections

Group therapy
Definition
Group therapy is a form of psychosocial treatment where a small group of patients meet regularly
to talk, interact, and discuss problems with each other
and the group leader (therapist).

Purpose
Group therapy attempts to give individuals a safe
and comfortable place where they can work out problems and emotional issues. Patients gain insight into
their own thoughts and behavior, and offer suggestions and support to others. In addition, patients who
have a difficult time with interpersonal relationships
GALE ENCYCLOPEDIA OF MEDICINE

can benefit from the social interactions that are a basic
part of the group therapy experience.

Precautions
Patients who are suicidal, homicidal, psychotic, or
in the midst of a major acute crisis are typically not
referred for group therapy until their behavior and
emotional state have stabilized. Depending on their
level of functioning, cognitively impaired patients (like
patients with organic brain disease or a traumatic
brain injury) may also be unsuitable for group therapy
intervention. Some patients with sociopathic traits are
not suitable for most groups.

Description
A psychologist, psychiatrist, social worker, or
other healthcare professional typically arranges and
conducts group therapy sessions. In some therapy
groups, two co-therapists share the responsibility of
group leadership. Patients are selected on the basis of
what they might gain from group therapy interaction
and what they can contribute to the group as a whole.
Therapy groups may be homogeneous or heterogeneous. Homogeneous groups have members with
similar diagnostic backgrounds (for example, they
may all suffer from depression). Heterogeneous
groups have a mix of individuals with different emotional issues. The number of group members varies
widely, but is typically no more than 12. Groups may
be time limited (with a predetermined number of sessions) or indefinite (where the group determines when
therapy ends). Membership may be closed or open to
new members once sessions begin.
The number of sessions in group therapy depends
on the makeup, goals, and setting of the group. For
example, a therapy group that is part of a substance
abuse program to rehabilitate inpatients would be
called short-term group therapy. This term is used
because, as patients, the group members will only be
in the hospital for a relatively short period of time.
Long-term therapy groups may meet for six months, a
year, or longer. The therapeutic approach used in
therapy depends on the focus of the group and the
psychological training of the therapist. Some common
techniques include psychodynamic, cognitive-behavioral, and Gestalt therapy.
In a group therapy session, group members are
encouraged to openly and honestly discuss the issues
that brought them to therapy. They try to help other
group members by offering their own suggestions,
insights, and empathy regarding their problems.
1647

Group therapy

Prevention

Group therapy
Group therapy is practiced in a variety of settings, including both inpatient and outpatient facilities, and is used to treat anxiety,
mood, and personality disorders as well as psychoses. (Photo Researchers, Inc. Reproduced by permission.)

There are no definite rules for group therapy, only that
members participate to the best of their ability.
However, most therapy groups do have some basic
ground rules that are usually discussed during the
first session. Patients are asked not to share what
goes on in therapy sessions with anyone outside of
the group. This protects the confidentiality of the
other members. They may also be asked not to see
other group members socially outside of therapy
because of the harmful effect it might have on the
dynamics of the group.
The therapist’s main task is to guide the group in
self-discovery. Depending on the goals of the group
and the training and style of the therapist, he or she
may lead the group interaction or allow the group to
take their own direction. Typically, the group leader
does some of both, providing direction when the group
gets off track while letting them set their own agenda.
The therapist may guide the group by simply reinforcing the positive behaviors they engage in. For example, if a group member shows empathy to another
member, or offers a constructive suggestion, the therapist will point this out and explain the value of these
1648

actions to the group. In almost all group therapy situations, the therapist will attempt to emphasize the common traits among group members so that members can
gain a sense of group identity. Group members realize
that others share the same issues they do.
The main benefit group therapy may have over
individual psychotherapy is that some patients behave
and react more like themselves in a group setting than
they would one-on-one with a therapist. The group
therapy patient gains a certain sense of identity and
social acceptance from their membership in the group.
Suddenly, they are not alone. They are surrounded by
others who have the same anxieties and emotional
issues that they have. Seeing how others deal with
these issues may give them new solutions to their
problems. Feedback from group members also offers
them a unique insight into their own behavior, and the
group provides a safe forum in which to practice new
behaviors. Lastly, by helping others in the group work
through their problems, group therapy members can
gain more self-esteem. Group therapy may also simulate family experiences of patients and will allow
family dynamic issues to emerge.
GALE ENCYCLOPEDIA OF MEDICINE

Cognitive-behavioral—A therapy technique that
focuses on changing beliefs, images, and thoughts
in order to change maladjusted behaviors.
Gestalt—A humanistic therapy technique that
focuses on gaining an awareness of emotions and
behaviors in the present rather than in the past.
Psychodynamic—A therapy technique that
assumes improper or unwanted behavior is caused
by unconscious, internal conflicts and focuses on
gaining insight into these motivations.

Self-help groups like Alcoholics Anonymous and
Weight Watchers fall outside of the psychotherapy
realm. These self-help groups do offer many of the
same benefits of social support, identity, and belonging that make group therapy effective for many. Selfhelp group members meet to discuss a common area of
concern (like alcoholism, eating disorders, bereavement, parenting). Group sessions are not run by a
therapist, but by a nonprofessional leader, group
member, or the group as a whole. Self-help groups
are sometimes used in addition to psychotherapy or
regular group therapy.

Preparation
Patients are typically referred for group therapy
by a psychologist or psychiatrist. Some patients may
need individual therapy first. Before group sessions
begin, the therapist leading the session may conduct
a short intake interview with the patient to determine
if the group is right for the patient. This interview will
also allow the therapist to determine if the addition of
the patient will benefit the group. The patient may be
given some preliminary information on the group
before sessions begin. This may include guidelines for
success (like being open, listening to others, taking
risks), rules of the group (like maintaining confidentiality), and educational information on what group
therapy is about.

Working through this termination phase of group
therapy is an important part of the treatment process.

Risks
Some very fragile patients may not be able to
tolerate aggressive or hostile comments from group
members. Patients who have trouble communicating
in group situations may be at risk for dropping out of
group therapy. If no one comments on their silence or
makes an attempt to interact with them, they may
begin to feel even more isolated and alone instead of
identifying with the group. Therefore, the therapist
usually attempts to encourage silent members to participate early on in treatment.

Normal results
Studies have shown that both group and individual psychotherapy benefit about 85% of the patients
that participate in them. Optimally, patients gain a
better understanding of themselves, and perhaps a
stronger set of interpersonal and coping skills through
the group therapy process. Some patients may continue therapy after group therapy ends, either individually or in another group setting.
Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.

Paula Anne Ford-Martin

Growth hormone suppression test see
Growth hormone tests

Growth hormone tests
Definition

Aftercare
The end of long-term group therapy may cause
feelings of grief, loss, abandonment, anger, or rejection in some members. The group therapist will
attempt to foster a sense of closure by encouraging
members to explore their feelings and use newly
acquired coping techniques to deal with them.
GALE ENCYCLOPEDIA OF MEDICINE

Growth hormone (hGH), or somatotropin, is a
hormone responsible for normal body growth and
development by stimulating protein production in
muscle cells and energy release from the breakdown
of fats. Tests for growth hormone include
Somatotropin hormone test, Somatomedin C,
Growth hormone suppression test (glucose loading
1649

Growth hormone tests

KEY TERMS

Growth hormone tests

test), and Growth hormone stimulation test (Arginine
test or Insulin tolerance test).

Purpose
Growth hormone tests are ordered for the following reasons:


to identify growth deficiencies, including delayed
puberty and small stature in adolescents that result
from pituitary or thyroid malfunction



to aid in the diagnosis of hyperpituitarism that is
evident in gigantism or acromegaly



to screen for inadequate or reduced pituitary gland
function



to assist in the diagnosis of pituitary tumors or
tumors related to the hypothalamus, an area of the
brain



to evaluate hGH therapy

Precautions
Taking certain drugs such as amphetamines,
dopamine, corticosteroids, and phenothiazines may
increase and decrease growth hormone secretion,
respectively. Other factors influencing hGH secretion
include stress, exercise, diet, and abnormal glucose
levels. These tests should not be done within a week
of any radioactive scan.

Description
Several hormones play important roles in human
growth. The major human growth hormone (hGH), or
somatotropin, is a protein made up of 191 amino acids
that is secreted by the anterior pituitary gland and
coordinates normal growth and development. Human
growth is characterized by two spurts, one at birth and
the other at puberty. hGH plays an important role at
both of these times. Normal individuals have measurable levels of hGH throughout life. Yet levels of hGH
fluctuate during the day and are affected by eating and
exercise. Receptors that respond to hGH exist on cells
and tissues throughout the body. The most obvious
effect of hGH is on linear skeletal development. But
the metabolic effects of hGH on muscle, the liver, and
fat cells are critical to its function. Surprisingly, a 2004
study reported that obese people have lower-thannormal levels of human growth hormone in their
bodies. Humans have two forms of hGH, and the
functional difference between the two is unclear. They
are both formed from the same gene, but one lacks the
amino acids in positions 32–46.
1650

hGH is produced in the anterior portion of the
pituitary gland by somatotrophs under the control of
hormonal signals in the hypothalamus. Two hypothalamic hormones regulate hGH; they are growth hormone-releasing hormone (GHRH) and growth
hormone—inhibiting hormone (GHIH). When blood
glucose levels fall, GHRH triggers the secretion of
stored hGH. As blood glucose levels rise, GHRH
release is turned off. Increases in blood protein levels
trigger a similar response. As a result of this hypothalamic feedback loop, hGH levels fluctuate throughout
the day. Normal plasma hGH levels average 1–3 ng/ML
with peaks as high as 60 ng/ML. In addition, plasma
glucose and amino acid availability for growth is also
regulated by the hormones adrenaline, glucagon, and
insulin.
Most hGH is released at night. Peak spikes of
hGH release occur around 10 P.M., midnight, and
2 A.M. The logic behind this night-time release is
that most of hGH’s effects are controlled by other
hormones, including the somatomedins, IGH-I and
IGH-II. As a result, the effects of hGH are spread
out more evenly during the day.
A number of hormonal conditions can lead to
excessive or diminished growth. Because of its critical
role in producing hGH and other hormones, an
abnormal pituitary gland will often yield altered
growth. Dwarfism (very small stature) can be due to
underproduction of hGH, lack of IGH-I, or a flaw in
target tissue response to either of these growth hormones. Overproduction of hGH or IGH-I, or an exaggerated response to these hormones can lead to
gigantism or acromegaly, both of which are characterized by a very large stature.
Gigantism is the result of hGH overproduction in
early childhood leading to a skeletal height up to 8 feet
(2.5m) or more. Acromegaly results when hGH is
overproduced after the onset of puberty. In this condition, the epiphyseal plates of the long bone of the
body do not close, and they remain responsive to
additional stimulated growth by hGH. This disorder
is characterized by an enlarged skull, hands and feet,
nose, neck, and tongue.
Somatotropin
Somatotropin is used to identify hGH deficiency
in adolescents with short stature, delayed sexual
maturity, and other growth deficiencies. It also
aids in documenting excess hGH production that is
responsible for gigantism or acromegaly, and confirms
underactivity or overproduction of the pituitary gland
(hypopituitarism or hyperpituitarism). However, due
GALE ENCYCLOPEDIA OF MEDICINE

Somatomedin C
The somatomedin C test is usually ordered to
detect pituitary abnormalities, hGH deficiency, and
acromegaly. Also called insulin-like growth factor
(IGF-1), somatomedin C is considered a more accurate reflection of the blood concentration of hGH
because such variables as time of day, activity levels,
or diet do not influence the results. Somatomedin C is
part of a group of peptides, called somatomedins,
through which hGH exerts its effects. Because it circulates in the bloodstream bound to long-lasting proteins, it is more stable than hGH. Levels of
somatomedin C depend on hGH levels, however. As
a result, somatomedin C levels are low when hGH
levels are deficient. Abnormally low test results of
somatomedin C require an abnormally reduced or
absent hGH during an hGH stimulation test in order
to diagnose hGH deficiency. Nonpituitary causes of
reduced somatomedin C include malnutrition, severe
chronic illness, severe liver disease, hypothyroidism,
and Laron’s dwarfism.
Growth hormone stimulation test
The hGH stimulation test, also called hGH
Provocation test, Insulin Tolerance, or Arginine test,
is performed to test the body’s ability to produce
human growth hormone, and to identify suspected
hGH deficiency. A normal patient can have low
hGH levels, but if hGH is still low after stimulation,
a diagnosis can be more accurately made.
Insulin-induced hypoglycemia (via intravenous
injection of insulin) stimulates hGH and corticotropin
secretion as well. If such stimulation is unsuccessful,
then there is a malfunction of the anterior pituitary
gland. Blood samples may be obtained following an
energetic exercise session lasting 20 minutes.
A substance called hGH-releasing factor has
recently been used for hGH stimulation. This
approach promises to be more accurate and specific
for hGH deficiency caused by the pituitary. Growth
GALE ENCYCLOPEDIA OF MEDICINE

hormone deficiency is also suspected when x ray determination of bone age indicates retarded growth in
comparison to chronologic age. At present, the best
method to identify hGH-deficient patients is a positive
stimulation test followed by a positive response to a
therapeutic trial of hGH.
Growth hormone suppression test
Also called the glucose loading test, this procedure
is used to evaluate excessive baseline levels of human
growth hormone, and to confirm diagnosis of gigantism in children and acromegaly in adults. The procedure requires two different blood samples, one drawn
before the administration of 100 g of glucose (by
mouth), and a second sample two hours after glucose
ingestion.
Normally, a glucose load suppresses hGH secretion. In a patient with excessive hGH levels, failure of
suppression indicates anterior pituitary dysfunction
and confirms a diagnosis of acromegaly and
gigantism.

Preparation
Somatotropin: This test requires a blood sample. The patient should be fasting (nothing to eat or
drink from midnight the night before the test).
Stress and/or exercise increases hGH levels, so the
patient should be at complete rest for 30 minutes
before the blood sample is drawn. If the physician
has requested two samples, they should be drawn
on consecutive days at approximately the same
time on both days, preferably between 6 A.M. and
8 A .M .
Somatomedin C: This test requires a blood sample. The patient should have nothing to eat or drink
from midnight the night before the test.
Growth hormone stimulation: This test requires
intravenous administration of medications and the
withdrawal of frequent blood samples, which are
obtained at 0, 60, and 90 minutes after injection of
arginine and/or insulin. The patient should have nothing to eat or drink after midnight the night before
the test.
Growth hormone suppression: This test
requires two blood samples, one before the test
and another two hours after administration of 100 g
of glucose solution by mouth. The patient should
have nothing to eat or drink after midnight, and
physical activity should be limited for 10–12 hours
before the test.
1651

Growth hormone tests

to the episodic secretion of hGH, as well as hGH
production in response to stress, exercise, or other
factors, random assays are not an adequate determination of hGH deficiency. To negate these variables
and obtain more accurate readings, a blood sample
can be drawn one to 1.5 hours after sleep (hGH levels
increase during sleep), or strenuous exercise can be
performed for 30 minutes before blood is drawn
(hGH levels increase after exercise). The hGH levels
at the end of an exercise period are expected to be
maximal.

Growth hormone tests

Risks
Growth hormone stimulation: Only minor discomfort is associated with this test, and results from
the insertion of the IV line and the low blood sugar
(hypoglycemia) induced by the insulin injection. Some
patients may experience sleepiness, sweating and/or
nervousness, all of which can be corrected after the
test by ingestion of cookies, juice, or a glucose infusion. Severe cases of hypoglycemia may cause ketosis
(excessive amounts of fatty acid byproducts in the
body), acidosis (a disturbance of the body’s acid-base
balance), or shock. With the close observation
required for the test, these are unlikely.
Growth hormone suppression: Some patients
experience nausea after the administration of this
amount of glucose. Ice chips can alleviate this
symptom.

Normal results
Normal results may vary from laboratory to
laboratory but are usually within the following ranges:
Somatotropin:


men: 5 ng/ml



women: less than 10 ng/ml



children: 0–10 ng/ml



newborn: 10–40 ng/ml.

KEY TERMS
Acromegaly—A rare disease resulting from excessive growth hormone caused by a benign tumor. If
such a tumor develops within the first 10 years of
life, the result is gigantism (in which growth is
accelerated) and not acromegaly. Symptoms
include coarsening of the facial features, enlargement of the hands, feet, ears, and nose, jutting of
the jaw, and a long face.
Dwarfism, pituitary—Short stature. When caused
by inadequate amounts of growth hormone (as
opposed to late growth spurt or genetics), hGH
deficiency results in abnormally slow growth and
short stature with normal proportions.
Gigantism—Excessive growth, especially in
height, resulting from overproduction during childhood or adolescence of growth hormone by a pituitary tumor. Untreated, the tumor eventually
destroys the pituitary gland, resulting in death during early adulthood. If the tumor develops after
growth has stopped, the result is acromegaly, not
gigantism.
Pituitary gland—The pituitary is the most important of the endocrine glands (glands that release
hormones directly into the bloodstream).
Sometimes referred to as the ‘‘master gland,’’ the
pituitary regulates and controls the activities of
other endocrine glands and many body processes.

Somatomedin C:


adult: 42–110 ng/ml



Child:



0–8 years: Girls 7–110 ng/ml; Boys 4–87 ng/ml



9–10 years: Girls 39–186 ng/ml; Boys 26–98 ng/ml



11–13 years: Girls 66–215 ng/ml; Boys 44–207 ng/ml



14–16 years: Girls 96–256 ng/ml; Boys 48 255 ng/ml.

Growth hormone stimulation: greater than
10 ng/ml.
Growth hormone suppression: Normally, glucose
suppresses hGH to levels of undetectable to 3 ng/ml in
30 minutes to two hours. In children, rebound stimulation may occur after two to five hours.

Abnormal results
Somatotropin hormone: Excess hGH is responsible for the syndromes of gigantism and acromegaly.
Excess secretion is stimulated by anorexia nervosa,
stress, hypoglycemia, and exercise. Decreased levels
1652

are seen in hGH deficiency, dwarfism, hyperglycemia,
failure to thrive, and delayed sexual maturity.
Somatomedin C: Increased levels contribute to
the syndromes of gigantism and acromegaly. Stress,
major surgery, hypoglycemia, starvation, and exercise
stimulate hGH secretion, which in turn stimulates
somatomedin C.
Growth hormone stimulation: Decreased levels
are seen in pituitary deficiency and hGH deficiency.
Diseases of the pituitary can result in failure of the
pituitary to secrete hGH and/or all the pituitary hormones. As a result, the hGH stimulation test will fail to
stimulate hGH secretion.
Growth hormone suppression: The acromegaly
syndrome elevates base hGH levels to 75 ng/ml,
which in turn are not suppressed to less than 5 ng/ml
during the test. Excess hGH secretion may cause
unchanged or rising hGH levels in response to glucose
loading, confirming a diagnosis of acromegaly or
GALE ENCYCLOPEDIA OF MEDICINE

responses seem to be the same as those with more
detailed imaginings.
Patients who feel uncomfortable ‘‘opening up’’ in
a traditional therapist-patient session may feel more at
ease with a self-directed therapy like guided imagery.

Resources
PERIODICALS

‘‘Weight-loss Hormone.’’ Better Nutrition (May 2004): 32.

Janis O. Flores
Teresa G. Odle

G6PD deficiency see Glucose-6-phosphate
dehydrogenase deficiency
Guaifenesin see Expectorants

Guided imagery
Definition
Guided imagery is the use of relaxation and mental visualization to improve mood and/or physical
well-being.

Purpose
The connection between the mind and physical
health has been well documented and extensively studied. Positive mental imagery can promote relaxation
and reduce stress, improve mood, control high blood
pressure, alleviate pain, boost the immune system, and
lower cholesterol and blood sugar levels. Through
guided imagery techniques, patients can learn to control functions normally controlled by the autonomic
nervous system, such as heart rate, blood pressure,
respiratory rate, and body temperature.
One of the biggest benefits of using guided imagery as a therapeutic tool is its availability. Imagery
can be used virtually anywhere, anytime. It is also an
equal opportunity therapy. Although some initial
training in the technique may be required, guided
imagery is accessible to virtually everyone regardless
of economic status, education, or geographical
location.
Guided imagery also gives individuals a sense of
empowerment, or control. The technique is induced by
a therapist who guides the patient. The resulting mental imagery used is solely a product of the individual’s
imagination. Some individuals have difficulty imagining. They may not get actual clear images but perhaps
vague feelings about the guided journey. However
these individuals’ brains and nervous systems
GALE ENCYCLOPEDIA OF MEDICINE

Description
Guided imagery is simply the use of one’s imagination to promote mental and physical health. It can
be self-directed, where the individual puts himself into
a relaxed state and creates his own images, or directed
by others. When directed by others, an individual
listens to a therapist, video, or audiotaped exercise
that leads him through a relaxation and imagery exercise. Some therapists also use guided imagery in group
settings.
Guided imagery is a two-part process. The first
component involves reaching a state of deep relaxation through breathing and muscle relaxation techniques. During the relaxation phase, the person closes
her eyes and focuses on the slow, in and out sensation
of breathing. Or, she might focus on releasing the
feelings of tension from her muscles, starting with the
toes and working up to the top of the head. Relaxation
tapes often feature soft music or tranquil, natural
sounds such as rolling waves and chirping birds in
order to promote feelings of relaxation.
Once complete relaxation is achieved, the second
component of the exercise is the imagery, or visualization, itself. There are a number of different types of
guided imagery techniques, limited only by the imagination. Some commonly used types include relaxation
imagery, healing imagery, pain control imagery, and
mental rehearsal.
Relaxation imagery
Relaxation imagery involves conjuring up pleasant, relaxing images that rest the mind and body.
These may be experiences that have already happened,
or new situations.
Healing imagery
Patients coping with diseases and injuries can
imagine cancer cells dying, wounds healing, and the
body mending itself. Or, patients may picture themselves healthy, happy, and symptom-free. Another
healing imagery technique is based on the idea of qi,
or energy flow, an idea borrowed from traditional
Chinese medicine. Chinese medicine practitioners
believe that illness is the result of a blockage or slowing
of energy flow in the body. Individuals may use guided
1653

Guided imagery

gigantism. In such cases, verification of results is
required by repeating the test after a one-day rest.

Guided imagery

imagery to imagine energy moving freely throughout
the body as a metaphor for good health.
Pain control imagery
Individuals can control pain through several imagery techniques. One method is to produce a mental
image of the pain and then transform that image into
something less frightening and more manageable.
Another is to imagine the pain disappearing, and the
patient as completely pain-free. Or, one may imagine
the pain as something over which he has complete
control. For example, patients with back problems
may imagine their pain as a high voltage electric current surging through their spine. As they use guided
imagery techniques, they can picture themselves
reaching for an electrical switch and turning down
the power on the current to alleviate the pain.

KEY TERMS
Aromatherapy—The therapeutic use of plantderived, aromatic essential oils to promote physical
and psychological well-being.
Autonomic nervous system—The part of the nervous system that controls so-called involuntary
functions such as heart rate, salivary gland
secretion, respiratory function, and pupil
dilation.

attempt to use guided imagery while driving or operating heavy machinery.

Side effects
Mental rehearsal
Mental rehearsal involves imagining a situation or
scenario and its ideal outcome. It can be used to reduce
anxiety about an upcoming situation, such as labor
and delivery, surgery, or even a critical life event such
as an important competition or a job interview.
Individuals picture themselves going through each
step of the anxiety-producing event and then successfully completing it.

Preparations
For a successful guided imagery session, individuals should select a quiet, relaxing location where
there is a comfortable place to sit or recline. If the
guided imagery session is to be prompted with an
audiotape or videotape, a stereo, VCR, or portable
tape player should be available. Some people find that
quiet background music improves their imagery
sessions.
The session, which can last anywhere from a few
minutes to an hour, should be uninterrupted. Taking
the phone off the hook and asking family members for
solitude can ensure a more successful and relaxing
session.
Imagery combined with other relaxation techniques such as yoga, massage, or aromatherapy can
greatly enhance the effects of these therapies. It can
be done virtually anywhere.

Guided imagery can induce sleepiness, and some
individuals may fall asleep during a session. Other
than this, there are no known adverse side effects to
guided imagery.

Research and general acceptance
Use of guided imagery is a widely accepted
practice among mental healthcare providers and is
gaining acceptance as a powerful pain control tool
across a number of medical disciplines. Results of
a study conducted at The Cleveland Clinic
Foundation and published in 1999 found that cardiac surgery patients who used a guided imagery
tape prior to surgery experienced less pain and
anxiety. These patients also left the hospital earlier
following surgery than patients who used pain
medication only.
Another study conducted by Harvard Medical
School researchers found that for more than 200
patients undergoing invasive vascular or renal surgery,
guided imagery controlled pain and anxiety more
effectively than medication alone.
Resources
BOOKS

Battino, Rubin. Guided Imagery and Other Approaches to
Healing. Carmarthen, United Kingdom: Crown House
Publishing, 2000.
PERIODICALS

Precautions
Because of the state of extreme relaxation
involved in guided imagery, individuals should never
1654

Lang, Elvira, et al. ‘‘Adjunctive non-pharmacological
analgesia for invasive medical procedures: a randomized trial.’’ The Lancet. 355, no. 9214, (April 2000):
1486-1490.
GALE ENCYCLOPEDIA OF MEDICINE

The Academy for Guided Imagery. P.O. Box 2070, Mill
Valley, CA 94942. (800) 726-2070.
OTHER

Brennan, Patricia. ‘‘Stress First Aid Kit.’’ (Guided imagery
audiotape set.) Available from Inside Out Publishing at
(888) 727-3296 or <http://www.facingthedawn.com>.

Paula Anne Ford-Martin

Guillain-Barré syndrome
Definition
Guillain-Barré syndrome (GBS) causes progressive muscle weakness and paralysis (the complete
inability to use a particular muscle or muscle group),
which develops over days or up to four weeks, and
lasts several weeks or even months.

Description
The classic scenario in GBS involves a patient who
has just recovered from a typical, seemingly uncomplicated viral infection. Symptoms of muscle weakness
appear one to four weeks later. The most common
preceding infections are cytomegalovirus, herpes,
Epstein-Barr virus, and viral hepatitis. A gastrointestinal infection with the bacteria Campylobacter jejuni is
also common and may cause a severe type of GBS
from which it is particularly difficult to recover.
About 5% of GBS patients have a surgical procedure
as a preceding event. Patients with lymphoma, systemic lupus erythematosus, or AIDS have a higher
than normal risk of GBS. Other GBS patients have
recently received an immunization, while still others
have no known preceding event. In 1976–77, there was
a vastly increased number of GBS cases among people
who had been recently vaccinated against the Swine
flu. The reason for this phenomenon has never been
identified, and no other flu vaccine has caused such an
increase in GBS cases.

Causes and symptoms
The cause of the weakness and paralysis of GBS is
the loss of myelin, which is the material that coats
nerve cells (the loss of myelin is called demyelination).
Myelin is an insulating substance which is wrapped
around nerves in the body, serving to speed conduction of nerve impulses. Without myelin, nerve
GALE ENCYCLOPEDIA OF MEDICINE

conduction slows or stops. GBS has a short, severe
course. It causes inflammation and destruction of the
myelin sheath, and it disturbs multiple nerves.
Therefore, it is considered an acute inflammatory
demyelinating polyneuropathy.
The reason for the destruction of myelin in GBS is
unknown, although it is thought that the underlying
problem is autoimmune in nature. An autoimmune
disorder is one in which the body’s immune system,
trained to fight against such foreign invaders as viruses
and bacteria, somehow becomes improperly programmed. The immune system becomes confused,
and is not able to distinguish between foreign invaders
and the body itself. Elements of the immune system
are unleashed against areas of the body, resulting in
damage and destruction. For some reason, in the case
of GBS, the myelin sheath appears to become a target
for the body’s own immune system.
The first symptoms of GBS consist of muscle
weakness (legs first, then arms, then face), accompanied by prickly, tingling sensations (paresthesias).
Symptoms affect both sides of the body simultaneously, a characteristic that helps distinguish GBS
from other causes of weakness and paresthesias.
Normal reflexes are first diminished, then lost. The
weakness eventually affects all the voluntary muscles, resulting in paralysis. When those muscles
necessary for breathing become paralyzed, the
patient must be placed on a mechanical ventilator
which takes over the function of breathing. This
occurs about 30% of the time. Very severely ill
GBS patients may have complications stemming
from other nervous system abnormalities which can
result in problems with fluid balance in the body,
severely fluctuating blood pressure, and heart
rhythm irregularities.

Diagnosis
Diagnosis of GBS is made by looking for a particular cluster of symptoms (progressively worse muscle
weakness and then paralysis), and by examining the
fluid that bathes the brain and spinal canal through
cerebrospinal fluid (CSF) analysis. This fluid is
obtained by inserting a needle into the lower back
(lumbar region). When examined in a laboratory, the
CSF of a GBS patient will reveal a greater-than-normal quantity of protein, with normal numbers of white
blood cells and a normal amount of sugar.
Electrodiagnostic studies may show slowing or block
of conduction in nerve endings in parts of the body
other than the brain. Minor abnormalities will be present in 90% of patients.
1655

Guillain-Barré syndrome

ORGANIZATIONS

Guinea worm infection

Prognosis

KEY TERMS
Autoimmune—The body’s immune system directed against the body itself.
Demyelination—Disruption or destruction of the
myelin sheath, leaving a bare nerve. Results in a
slowing or stopping of impulses traveling along
that nerve.
Inflammatory—Having to do with inflammation,
the body’s response to either invading foreign substances (such as viruses or bacteria) or to direct
injury of body tissue.
Myelin—The substance that is wrapped around
nerves, and which is responsible for speed and
efficiency of impulses traveling through those
nerves.

Treatment
There is no direct treatment for GBS. Instead,
treatments are used that support the patient with the
disabilities caused by the disease. The progress of
paralysis must be carefully monitored, in order to
provide mechanical assistance for breathing if it
becomes necessary. Careful attention must also be
paid to the amount of fluid the patient is taking in by
drinking and eliminating by urinating. Blood pressure, heart rate, and heart rhythm also must be
monitored.
A procedure called plasmapheresis, performed
early in the course of GBS, has been shown to shorten
the course and severity of GBS. Plasmapheresis consists of withdrawing the patient’s blood, passing it
through an instrument that separates the different
types of blood cells, and returning all the cellular
components (red and white blood cells and platelets)
along with either donor plasma or a manufactured
replacement solution. This is thought to rid the
blood of the substances that are attacking the patient’s
myelin.
It has also been shown that the use of high doses of
immunoglobulin given intravenously (by drip through
a needle in a vein) may be just as helpful as plasmapheresis. Immunoglobulin is a substance naturally
manufactured by the body’s immune system in
response to various threats. It is interesting to note
that corticosteroid medications (such as prednisone),
often the mainstay of anti-autoimmune disease treatment, are not only unhelpful, but may in fact be harmful to patients with GBS.
1656

About 85% of GBS patients make reasonably
good recoveries. However, 30% of adult patients,
and a greater percentage of children, never fully regain
their previous level of muscle strength. Some of these
patients suffer from residual weakness, others from
permanent paralysis. About 10% of GBS patients
begin to improve, then suffer a relapse. These patients
suffer chronic GBS symptoms. About 5% of all GBS
patients die, most from cardiac rhythm disturbances.
Patients with certain characteristics tend to have a
worse outcome. These include people of older age,
those who required breathing support with a mechanical ventilator, and those who had their worst symptoms within the first seven days.

Prevention
Because so little is known about what causes GBS
to develop, there are no known methods of
prevention.
Resources
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave.,
St. Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.
Guillain-Barré Syndrome Foundation International. PO
Box 262, Wynnewood, PA 19096. (610) 667-0131. (610)
667-0131. <http://www.webmast.com/gbs>.

Rosalyn Carson-DeWitt, MD

Guinea worm infection
Definition
Infection occurs when the parasitic guinea worm
resides within the body. Infection is not apparent until
a pregnant female worm prepares to expel embryos.
The infection is rarely fatal, but the latter stage is
painful. The infection is also referred to as dracunculiasis, and less commonly as dracontiasis.

Description
Before the early 1980s, guinea worms infected
10–15 million people annually in central Africa and
parts of Asia. By 1996, worldwide incidence of infection fell to fewer than 153,000 cases per year.
GALE ENCYCLOPEDIA OF MEDICINE

To survive, guinea worms require three things:
water during the embryo stage, an intermediate host
during early maturation, and a human host during
adulthood. In bodies of water, such as ponds, guinea
worm embryos are eaten by tiny, lobster-like water
fleas. Once ingested, the embryos mature into larvae.
Humans become hosts by consuming water containing infected water fleas. Once in the human intestine, larvae burrow into surrounding tissue. After
three to four, the worms mate. Males die soon after,
but pregnant females continue to grow. As adults,
each threadlike worm can be three feet long and harbor three million embryos. More than one guinea
worm can infect a person at the same time.
About eight months later, the female prepares to
expel mature embryos by migrating toward the skin
surface. Until this point, most people are unaware that
they are infected. Extreme pain occurs as the worm
emerges from under the skin, often around the infected
person’s ankle. The pain is temporarily relieved by
immersing the area in water, an act that contaminates
the water and starts the cycle again.

KEY TERMS
Guinea worm embryo—The guinea worm at its earliest life stage prior to or shortly after being expelled
from an adult female worm.
Guinea worm larvae—The guinea worm during its
middle life stage as it matures within a water flea.
The larvae can only grow to adulthood within a
human host.
Host—With regard to guinea worm infection, either
the water flea or human from which the worm gets
nourishment and shelter as it matures.
Secondary infection—An illness–typically caused
by bacteria–that follows from a guinea worm
infection.

Modern medicine offers safe surgical removal of
the guinea worm, and drug therapy can prevent infection and pain. Using drugs to combat the worms has
had mixed results.

Prognosis
Causes and symptoms
Dracunculus medinensis, or guinea worm, causes
infection. Symptoms are commonly absent until a
pregnant worm prepares to expel embryos. By secreting an irritating chemical, the worm causes a blister to
form on the skin surface. This chemical also causes
nausea, vomiting, dizziness, and diarrhea. The blister is
accompanied by a burning, stabbing pain and can
form anywhere on the body; but, the usual site is the
lower leg or foot. Once the blister breaks, an open sore
remains until the worm has expelled all the embryos.

Diagnosis
Guinea worm infection is identified by the
symptoms.

Treatment
Most people infected with guinea worm rely on
traditional medicine. The worm is extracted by gently
and gradually pulling the worm out and winding it
around a small strip of wood. Surgical removal is
possible, but rarely done in rural areas. Extraction is
complemented by herbs and oils to treat the wound
site. Such treatment can ease extraction and may help
prevent secondary infections.
GALE ENCYCLOPEDIA OF MEDICINE

If the worm is completely removed, the wound
heals in approximately two to four weeks.
However, if a worm emerges from a sensitive
area, such as the sole of a foot, or if several
worms are involved, healing requires more time.
Recovery is also complicated if the worm breaks
during extraction. Serious secondary infections frequently occur in such situations. There is the risk
of permanent disability in some cases, and having
one guinea worm infection does not confer immunity against future infections.

Prevention
Guinea worn infection is prevented by disrupting
transmission. Wells and other protected water sources
are usually safe from being contaminated with worm
embryos. In open water sources, poisons may be used
to kill water fleas. Otherwise, water must be boiled or
filtered.
Resources
OTHER

World Health Organization. June 7, 1998. <http://
www.who.int/home-page/index.en.shtml>.

Julia Barrett
1657

Guinea worm infection

Complete eradication of guinea worm infection is a
goal of international water safety programs.

Gulf War syndrome

Gulf War syndrome
Definition
Gulf War syndrome describes a wide spectrum of
illnesses and symptoms ranging from asthma to sexual
dysfunction that have been reported by U.S. and U.S.
allied soldiers who served in the Persian Gulf War in
1990–1991.

Description
Between 1994 and 1999, 145 federally funded
research studies on Gulf War-related illnesses were
undertaken at a cost of over $133 million. Despite
this investment and the data collected from over
100,000 veterans who have registered with the
Department of Defense (DOD) and/or Veterans
Administration (VA) as having Gulf War-related illnesses, there is still much debate over the origin and
nature of Gulf War syndrome. As of early 2001, the
DOD has failed to establish a definite cause for the
disorder. Veterans who have the illness experience a
wide range of debilitating symptoms that elude a single diagnosis. Common symptoms include fatigue,
trouble breathing, headaches, disturbed sleep, memory loss, and lack of concentration. Similar experiences among Gulf War veterans have been reported
in the United Kingdom and Canada.

Causes and symptoms
There is much current debate over a possible causative agent for Gulf War syndrome other than the stress
of warfare. Intensive efforts by the Veterans
Administration and other public and private institutions
have investigated a wide range of potential factors.
These include chemical and biological weapons, the
immunizations and preventive treatments used to protect against them, smoke from oil well fires, exposure to
depleted uranium, and diseases endemic to the Arabian
peninsula. So far investigators have not approached a
consensus. In its final report released in December 2000,
the Presidential Special Oversight Board for
Department of Defense Investigations of Gulf War
Chemical and Biological Incidents cited combat stress
as a possible causative factor, but called for further
research. There is also a likelihood that U.S. and allied
forces were exposed to low levels of sarin and/or cyclosarin (nerve gases) released during the destruction of
Iraqi munitions at Kharnisiyah, Iraq, and that these
chemicals might be linked to the syndrome. In July
1997, the VA informed approximately 100,000 U.S. servicemen of their possible exposure to the nerve agents.
1658

In October 1999, the U.S. Pentagon released a
report that hypothesized that an experimental drug
known as pyriostigmine bromide (PB) might be linked
to the physical symptoms manifested in Gulf War
Syndrome. The experimental drug was given to U.S.
and Canadian troops during the war to protect
soldiers against the effects of the chemical nerve
agent soman. It has also been suggested that botulinum toxoid and anthrax vaccinations administered to
soldiers during the conflict may be responsible for
some manifestations of the syndrome.
Some studies have shown that Gulf War veterans
have a higher incidence of positive tests for
Mycoplasma fermentans, a bacteria, in their bloodstream. However, other clinical studies have not
found a link between the bacterial infection and Gulf
War-related illnesses.
Statistical analysis tells us that the following
symptoms are about twice as likely to appear in Gulf
War veterans than in their non-combat peers: depression, posttraumatic stress disorder (PTSD), chronic
fatigue, cognitive dysfunction (diminished ability to
calculate, order thoughts, evaluate, learn, and remember), bronchitis, asthma, fibromyalgia, alcohol abuse,
anxiety, and sexual discomfort. PTSD is the modern
equivalent of shell shock (World War I) and battle
fatigue (World War II). It encompasses most of the
psychological symptoms of war veterans, including
nightmares, panic at sudden loud noises, and inability
to adjust to peacetime living. Chronic fatigue syndrome
has a specific medical definition that attempts to separate common fatigue from a more disabling illness in
hope of finding a specific cause. Fibromyalgia is
another newly defined syndrome, and as such it has
arbitrarily rigid defining characteristics. These include
a certain duration of illness, a specified minimum
number of joint and muscle pain located in designated
areas of the body, sleep disturbances, and other associated symptoms and signs.
Researchers have identified three distinct syndromes and several variations in Gulf War veterans.
Type one patients suffer primarily from impaired
thinking. Type two patients have a greater degree of
confusion and ataxia (loss of coordination). Type
three patients were the most affected by joint pains,
muscle pains, and extremity paresthesias (unnatural
sensations like burning or tingling in the arms and
legs). In each of the three types, researchers found
different but measurable impairments on objective
testing of neurological function. The business of the
nervous system is much more complex and subtle than
other body functions. Measuring it requires equally
complex effort. The tests used in this study carefully
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Until there is a clear definition of the disease,
diagnosis is primarily an exercise in identifying those
Gulf War veterans who have undefined illness in an
effort to learn more about them and their symptoms.
Both the Department of Defense and the Veterans
Administration currently have programs devoted to
this problem. Both the DOD’s Comprehensive
Clinical Evaluation Program and the VA’s Persian
Gulf Registry provide free, in-depth medical evaluations to Gulf War veterans and their families. In addition to providing individual veterans with critical
medical care, these organizations use the cumulative
data from these programs to advance research on Gulf
War Syndrome itself.

KEY TERMS
Ataxia—Lack of coordination.
Caloric testing—Flushing warm and cold water
into the ear stimulates the labyrinth and causes
vertigo and nystagmus if all the nerve pathways
are intact.
Endemic—Always there.
Paresthesia—An altered sensation often described
as burning, tingling, or pin pricks.
Syndrome—Common features of a disease or features that appear together often enough to suggest
they may represent a single, as yet unknown, disease entity. When a syndrome is first identified, an
attempt is made to define it as strictly as possible,
even to the exclusion of some cases, in order to
separate out a pure enough sample to study. This
process is most likely to identify a cause, a positive
method of diagnosis, and a treatment. Later on, less
typical cases can be considered.

fermentans bacterial infection. However, a conclusive
link has not been clinically proven.

Prognosis
Treatment
Specific treatment awaits specific diagnosis and
identification of a causative agent. Meanwhile, veterans can benefit from the wide variety of supportive
and non-specific approaches to this and similar problems. There are many drugs available for symptomatic relief. Psychological counseling by those
specializing in this area can be immensely beneficial,
even life-saving for those contemplating suicide.
Veterans’ benefits are available for those who are
impaired by their symptoms.

Alternative treatment
The symptoms can be worked with using many
modalities of alternative health care. The key to working successfully with people living their lives with Gulf
War syndrome is long-term, ongoing care, whether it
be hypnotherapy, acupuncture, homeopathy, nutrition,
vitamin/mineral therapy, or bodywork.
Experimental treatment with antibiotics is advocated by some healthcare professionals who believe
that Gulf War illness is related to a Mycoplasma
GALE ENCYCLOPEDIA OF MEDICINE

The outlook for Persian Gulf War veterans is
unclear, but will hopefully improve as more information is gathered about the illness. Gradual return to a
functioning life may take many years of work and
much help. It is important to note that even in the
absence of an identifiable and curable cause, recovery
is possible.
Resources
BOOKS

Wheelwright, Jeff. The Irritable Heart. New York: W.W.
Norton & Co., 2001.
ORGANIZATIONS

The American Legion. Gulf War Veteran Issues. <http://
www.legion.org/gulftoc.htm>.
Office of the Special Assistant for Gulf War Illnesses. 5113
Leesburg Pike, Suite 901, Falls Church, VA, 22041.
(703) 578-8518. <http://www.gulflink.osd.mil>.
U.S. Department of Defense. Comprehensive Clinical
Evaluation Program (CCEP). (800) 796-9699.
Veterans Administration. Persian Gulf Medical Information
Helpline. 400 South 18th Street, St. Louis, Missouri
63103-2271. (800)749-8387.
1659

Gulf War syndrome

measured and compared localized nerve performance
at several different tasks against the same values in
normal subjects. Brain wave response to noise and
touch, eye muscle response to spinning, and caloric
testing (stimulation of the ear with warm and cold
water, which causes vertigo) were clearly different
between the normal and the test subjects. The
researchers concluded that there was ‘‘a generalized
injury to the nervous system.’’ Another research group
concluded their study by stating that there was ‘‘a
spectrum of neurologic injury involving the central,
peripheral, and autonomic nervous systems.’’

Gynecomastia

Veterans Administration. Persian Gulf Registry.
(800)PGW-VETS (800) 749-8387. <http://
www.va.gov>.

KEY TERMS

OTHER

Androgen—Male sex hormone.

Office of the Special Assistant for Gulf War Illnesses. Fourth
Annual Report: Office of the Special Assistant for Gulf
War Illnesses. Falls Church, VA: Office of the Special
Assistant for Gulf War Illnesses, 2000. <http://
www.gulflink.osd.mil/library/annual/
4thannual_report_jan01.htm>.

Cirrhosis—Diffuse scarring caused by alcohol or
chronic hepatitis often leading to liver failure.

Paula Anne Ford-Martin

Gum disease see Periodontal disease
Günther’s disease see Porphyrias

Gynecomastia
Definition
Gyne refers to female, and mastia refers to the
breast. Gynecomastia is strictly a male disease and is
any growth of the adipose (fatty) and glandular tissue
in a male breast. Not all breast growth in men is
considered abnormal, just excess growth.

Causes and symptoms
Breast growth is directed exclusively by female
hormones–estrogens. Although men have some estrogen in their system, it is usually insufficient to cause
much breast enlargement because it is counterbalanced by male hormones–androgens. Upsetting the
balance, either by more of one or less of the other,
results in the male developing female characteristics,
breast growth being foremost.
At birth both male and female infants will have
little breast buds from their mother’s hormones. These
recede until adolescence, when girls always, and boys
sometimes, have breast growth. At this time, the boy’s
breast growth is minimal, often one-sided and
temporary.
Extra or altered sex chromosomes can produce
intersex problems of several kinds. Breast growth
along with male genital development is seen in
Klinefelter syndrome–the condition of having an
extra X (female) chromosome–and a few other chromosomal anomalies. One of the several glands that
produce hormones can malfunction for reasons other
than chromosomes. Failure of androgen production is
as likely to produce gynecomastia as overabundant
1660

Estrogen—Sex hormone responsible for stimulating female sexual characteristics.
Klinefelter syndrome—A condition in a male characterized by having an extra X (female) chromosome and suffering from infertility and
gynecomastia.
Thyroid—A gland in the neck that makes thyroxin.
Thyroxin regulates the speed of metabolism.

estrogen production. Testicular failure and castration
can also be a cause. Some cancers and some benign
tumors can make estrogens. Lung cancer is known to
increase estrogens.
If the hormone manufacturing organs are functioning properly, problems can still arise elsewhere.
The liver is the principle chemical factory in the
body. Other organs like the thyroid and kidneys also
effect chemical processes. If any of these organs are
diseased, a chemical imbalance can result that alters
the manufacturing process. Men with cirrhosis of the
liver will often develop gynecomastia from increased
production of estrogens.
Finally, drugs can also cause breast enlargement.
Estrogens are given to men to treat prostate cancer
and a few other diseases. Marijuana and heroin,
along with some prescription drugs, have estrogen
effects in some men. On the list are methyldopa (for
blood pressure), cimetidine (for peptic ulcers), diazepam (Valium), antidepressants, and spironolactone
(a diuretic).

Diagnosis
Carefully feeling the area beneath the nipple of an
adolescent boy with breast enlargement will reveal a
discreet and sometimes tender lump the size of a fat
nickel or quarter. For more serious gynecomastia, the
underlying disease will require evaluation, if it is not
already well understood.

Treatment
This condition is usually not treated. If it is the
result of endocrine disease, hormone manipulations
may reduce the effects of the imbalance. There are a
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The progress of gynecomastia is determined by its
cause.

GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Wilson, Jean D. ‘‘Endocrine Disorders of the Breast.’’ In
Harrison’s Principles of Internal Medicine, edited
by Anthony S. Fauci, et al. New York: McGrawHill, 1997.

J. Ricker Polsdorfer, MD

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Gynecomastia

number of medical and surgical interventions possible.
Radiation of misbehaving organs and cancers is considered an effective treatment.

H
H-2 blockers
Definition
Histamine H-2 receptor blockers act by stopping
the pathway that leads to the secretion of stomach
acid. There are two kinds of pathways that react to
stimulation by histamine. Histamine is produced in
the body and released by mast cells in response to
some types of injury or to the presence of an antigen.
When histamine reaches the H-1 receptors, the reaction results in dilation of capillaries, leading to redness
and swelling, along with itching. These reactions can
be controlled with traditional antihistamines.
Histamine that reaches the H-2 receptors causes
increased secretion of stomach acid.

Purpose
H2 receptor blockers are used to treat conditions
associated with excess amounts of stomach acid,
although in some cases they have been replaced by
the proton pump inhibitors, which have a greater effect
on reducing acid secretions.
H2 receptor blockers are used to treat the following
conditions:


duodenal ulcer, as short term therapy and
maintenance



gastric ulcer, as short term therapy and maintenance



gastroesophageal reflux disease (GERD), including
endoscopically diagnosed erosive esophagitis



pathological hypersecretory conditions such as
Zollinger-Ellison syndrome, systemic mastocytosis,
and multiple endocrine adenomas



upper GI bleeding



heartburn, acid indigestion, and sour stomach

None of the drugs in this class has been approved
for use by children under the age of 12 years. However,
GALE ENCYCLOPEDIA OF MEDICINE

standard pediatric texts have reported on use by
infants and children.

Description
There are four H2 receptor blockers on the market. Although they all work in the same manner and
have similar effects, they are not all approved for the
same uses.
Cimetidine (Tagamet) is available in both prescription and over-the-counter forms. The oldest of
the group and the most studied, this drug is the least
potent of the H2 receptor blockers, which means that
higher dosages are required to provide comparable
effects. There is no evidence that higher potency
improves therapeutic results.
Cimetidine is the only drug in its class which is
approved for prevention of upper gastro-intestinal
bleeding. It has been reported on for a number of
uses, with varying degrees of success. Cimetidine, like
ranitidine, has shown some benefit in treatment of
colorectal cancer. Although some claims have been
made that cimetidine is useful in treatment of acetaminophen overdose, the evidence for this use is lacking,
and cimetidine should not be used. Because cimetidine
is a mild antiandrogen, it has been of some use in
treatment of hirsutism (abnormal growth of hair on a
woman’s face and body).
The three other H2 receptor blockers, famotidine
(Pepcid, Pepcid AC), nizatidine (Axid), and ranitidine
(Zantac), are similar in their uses. All are approved for
treatment of duodenal ulcer both acute treatment and
maintenance therapy, gastro-esophageal reflux disease, including erosive esophagitis and gastric ulcer
short term treatment, although in this group ranitidine
alone is approved for maintenance treatment.
In their over-the-counter (non-prescription) forms,
cimetidine and famotidine are approved for treatment
of heartburn, acid indigestion, and sour stomach.
1663

H-2 blockers

Drugs in this class are similar in other respects as
well. Although study results vary, cimetidine will
usually show its effects within one hour and last for
about five hours after a single dose; famotidine and
nizatidine also show effects within one hour but may
act for up to 12 hours at maximum dosing. Ranitidine
has a comparable onset of action and duration in
adults but may be slower in the elderly. Onset and
duration of action will vary with the individual, the
dose of medication, and the presence or absence of
food or antacids in the stomach.
When Facts and Comparisons, a widely used
on-line drug information resource, compared the
published reports on cure rates for duodenal ulcers,
it found that after eight weeks of treatment, all drugs
showed healing rates in the range of 82% to 95%.
These results were based on comparing separate
studies and did not represent comparative trials of
the drugs against each other.

Recommended dosage
Cimetidine doses for patients over the age of 12
years, for oral administration.










Short-term treatment of active duodenal ulcer: 800
mg at bedtime. Other dose regimens are sometimes
used.
Heartburn, acid indigestion, and sour stomach using
the over-the-counter product: 100 to 200 mg with
water when symptoms start. The dose may be
repeated once in 24 hours.
Prevention of heartburn, acid indigestion, and sour
stomach using the over-the-counter product: 100 to
200 mg with water up to one hour before eating food
or drinking beverages expected to cause symptoms.
Dose should not exceed 400 mg in 24 hours.
Treatment of hypersecretory conditions: 300 mg four
times a day, with meals and at bedtime.
Gastroesophageal reflux disease: 800 to 1600 mg a
day, divided into smaller doses. Treatment usually
lasts 12 weeks.

Famotidine doses for patients over the age of 12
years, for oral administration.


Treatment of duodenal ulcers: 40 mg once a day at
bedtime. If necessary, 20 milligrams two times a day
may be used.



Prevention of duodenal ulcers: 20 mg once a day at
bedtime.



Gastric ulcers: 40 mg once a day at bedtime.

1664



To treat heartburn, acid indigestion, and sour
stomach using the over-the-counter product: 10 mg
with water when symptoms start. The dose may be
repeated once in 24 hours.



Hypersecretory conditions: 20 mg every six hours.



Gastroesophageal reflux disease: 20 mg two times a
day, usually for up to six weeks.

Nizatidine doses for patients over the age of 12
years, for oral administration.


Treatment of duodenal or gastric ulcers: 300 mg once
a day at bedtime. Alternately, 150 mg two times a
day.



Prevention of duodenal ulcers: 150 mg once a day
at bedtime.



Prevention of heartburn, acid indigestion, and sour
stomach: 75 mg taken thirty to sixty minutes before
meals which may cause symptoms. The dose may be
repeated once in 24 hours.



Gastroesophageal reflux disease: 150 mg two times
a day.

Ranitidine doses for patients over the age of
12 years, for oral administration.


Duodenal ulcers, treatment: 150 mg two times a day.
Alternately, 300 mg once a day at bedtime.



Duodenal ulcers, prevention: 150 mg at bedtime.



Gastric ulcers, treatment: 150 mg two times a day.



Heartburn, acid indigestion, and sour stomach,
treatment: 75 mg with water when symptoms start.
The dose may be repeated once in 24 hours.



Heartburn, acid indigestion, and sour stomach, prevention: 75 mg with water taken thirty to sixty minutes before meals or beverages which may cause
symptoms. The dose may be repeated once in
24 hours.



Hypersecretory conditions: 150 mg two times a day.



Gastroesophageal reflux disease: 150 mg two times a
day. The dose may be increased as needed.

Precautions
Overall, the histamine H2 receptor blockers are a
safe class of drugs. However, some patients may be
particularly susceptible to adverse effects of these
drugs. H2 receptor blockers are metabolized in the
liver and excreted through the kidneys. Therefore,
patients with kidney or liver problems may require
reduced doses in order to maintain safe blood levels
of the drugs.
GALE ENCYCLOPEDIA OF MEDICINE

Allergic reactions to these drugs are rare but have
been reported.
The histamine H2 receptor blockers are
Pregnancy category B. There are no adequate and
well-controlled studies with these agents in pregnant
women. Women should use them only when clearly
needed and when the potential benefits outweigh the
potential hazards to the fetus. Cimetidine is known to
cross the placenta.
All drugs in this class are excreted into breast milk
and should not be taken by nursing women. Decide
whether to discontinue nursing, or discontinue the
drug, taking into account the importance of the drug
to the mother.
These drugs may mask the symptoms of stomach
cancer.

Side effects
Although side effects due to the H2 receptor
blockers are relatively rare and usually mild, a large
number of adverse effects have been reported, in part
because of the high use of these drugs. For example,
the most common single adverse effect of cimetidine
has been a 4% incidence of breast enlargement among
males taking the drug in high doses for hypersecretory
conditions. Similarly, the incidence of headache
among high-dose cimetidine patients was 3.5%.
Among patients taking lower doses, the frequency of
headache was 2.1% compared to 2.3% in a placebo
control group. Decreased white blood cell count was
reported in 1 in 1,000,000 patients.
The reported side effects from the H2 receptor
blocks are:


abdominal pain



back, leg, or stomach pain



bleeding or crusting sores on lips



blistering, burning, redness, scaling, or tenderness of
skin



blisters on palms of hands and soles of feet



changes in vision or blurred vision



coughing or difficulty in swallowing



dark-colored urine



dizziness

GALE ENCYCLOPEDIA OF MEDICINE



fainting



fast, pounding, or irregular heartbeat



fever and/or chills



flu-like symptoms



general feeling of discomfort or illness



hives



inflammation of blood vessels



joint pain



light-colored stools



mood or mental changes, including anxiety, agitation, confusion, hallucinations (seeing, hearing, or
feeling things that are not there), mental depression,
nervousness, or severe mental illness



muscle cramps or aches



nausea, vomiting, or loss of appetite



pain



peeling or sloughing of skin



red or irritated eyes



shortness of breath



skin rash or itching



slow heartbeat



sore throat



sores, ulcers, or white spots on lips, in mouth, or on
genitals



sudden difficult breathing



swelling of face, lips, mouth, tongue, or eyelids



swelling of hands or feet



swollen or painful glands



tightness in chest



troubled breathing, unusually slow or irregular
breathing



unusual bleeding or bruising



unusual tiredness or weakness



wheezing



yellow eyes or skin

H-2 blockers

Although the safety and effectiveness of H2
receptor blockers in patients over the age of 65
appears to be similar to that seen in younger patients,
age-associated reductions in kidney function may
lead to elevated blood levels.

Less frequently reported are


constipation



decreased sexual ability (especially in patients with
Zollinger-Ellison disease who have received high
doses of cimetidine for at least 1 year)



decrease in sexual desire
1665

H-2 blockers



diarrhea



difficult urination



dizziness



drowsiness



dryness of mouth or skin



headache



increased or decreased urination



increased sweating



loss of hair



ringing or buzzing in ears



runny nose



swelling of breasts or breast soreness in females and
males



trouble in sleeping

KEY TERMS
Duodenal—Pertaining to the first part of the small
intestine.
Gastric—Pertaining to the stomach.
Hirsutism—Abnormal growth of hair on a woman’s
face and body.
Histamine—A physiologically active compound
found in plant and animal tissue and released
from mast cells as part of an allergic reaction in
humans. It stimulates gastric secretion and causes
dilation of capillaries, constriction of bronchial
smooth muscle, and decreased blood pressure.
Hypersecretory—Excessive secretions, over production of stomach acid.
Mast cell—A cell found in connective tissue that
releases substances such as heparin and histamine
in response to injury or inflammation of bodily
tissues.
Peptic—Induced by or associated with the action
of digestive secretions.

Not all of these adverse effects have been reported
with all of the H2 receptor blockers, and some of the
adverse effects may not have been drug related.
However, because of the high similarity between
drugs in this class, any of the reported adverse effects
may be considered a possible result of therapy.

Ulcer—A slow-healing sore on the surface of a
mucous membrane, especially the membrane lining the stomach or other part of the digestive tract.

Interactions
Cimetidine and ranitidine are both metabolized in
the liver using the cytochrome P450 oxidase enzyme
system. Since the same enzymes metabolize many
drugs, taking two or more drugs that affect the same
group of enzymes may cause one of the drugs to be
retained in the body longer than would have been
expected. The following is a partial list of drugs
which may interact with cimetidine, or to a lesser
extent with ranitidine.


benzodiazepines, including Valium, Librium and
Xanax



caffeine



calcium channel blockers, including Adalat, Calan,
Procadia, and others



carbamazepine



chloroquine



labetolol



lidocaine



metoprolol



metronidazole



phenytoin



propranolol

1666

Zollinger-Ellizon syndrome—Severe peptic ulceration from excessive stomach acid production
stimulated by one or more tumors that produce a
powerful acid secretion.



quinidine



quinine



sulfonylureas (includes many of the drugs used to
treat diabetes)



theophyllines (used to treat asthma; Dyphylline, a
member of this group, does not interact with
cimetidine)



triamterene (a diuretic drug rarely used alone but
may be found in fixed combinations, including
Dyazide and Maxzide)



tricyclic antidepressants (a group that includes amitriptyline, imipramine, and others)



valproic acid



warfarin

Additional drugs may also interact with the H2
receptor blockers, particularly those which might have
a similar mechanism or action or adverse effects.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., ed. Merck Manual of Medical Information:
Home Edition. Riverside, NJ: Simon & Schuster, 2004.
Physicians’ Desk Reference 2005. Montvale, NJ: Thomson
Healthcare, 2004.
Robertson, Jason, et al. The Harriet Lane Handbook: A
Manual for Pediatric House Officers. Orlando, FL:
Mosby Inc., 2005.
PERIODICALS

Black, R. A., and D. A. Hill. ‘‘Over-the-counter medications
in pregnancy.’’ American Family Physician 67, no. 12
(June 15, 2003): 2517–24.
Chandramouli, J. ‘‘What is the most effective therapy for
preventing NSAID-induced gastropathy?’’ Journal of
Pain and Palliative Care Pharmacotherapy 16, no. 2
(2002): 23–36.
ORGANIZATION

American College of Gastroenterology. PO Box 342260,
Bethesda, MD 20827–2260. (301)263-9000.
<www.acg.gi.org>.
American Gastroenterological Association. 4930 Del Ray
Avenue, Bethesda, MD 20814. (301)654-2055.
<www.gastro.org>.

Samuel D. Uretsky, Pharm.D.

Habitual abortion see Recurrent miscarriage

Hair transplantation
Definition
Hair transplantation is a surgical procedure used
to treat baldness or hair loss. Typically, tiny patches of
scalp are removed from the back and sides of the head
and implanted in the bald spots in the front and top of
the head.

Purpose
Hair transplantation is a cosmetic procedure
performed on men (and occasionally on women) who
have significant hair loss, thinning hair, or bald spots
where hair no longer grows. In men, hair loss and
baldness are most commonly due to genetic factors
(a tendency passed on in families) and age. Male
pattern baldness, in which the hairline gradually
recedes to expose more and more of the forehead, is
the most common form. Men may also experience a
gradual thinning of hair at the crown or very top of
GALE ENCYCLOPEDIA OF MEDICINE

the skull. For women, hair loss is more commonly
due to hormonal changes and is more likely to be a
thinning of hair from the entire head. An estimated
50,000 men get transplants each year. Transplants can
also be done to replace hair lost due to burns, injury, or
diseases of the scalp.

Precautions
Although hair transplantation is a fairly simple
procedure, some risks are associated with any surgery.
It is important to inform the physician about any
medications currently being used and about previous
allergic reactions to drugs or anesthetic agents. Patients
with blood clotting disorders also need to inform their
physician before the procedure is performed.

Description
Hair transplantation surgery is performed by a
physician in an office, clinic, or hospital setting. Each
surgery lasts two to three hours during which approximately 250 grafts will be transplanted. A moderately
balding man may require up to 1,000 grafts to get good
coverage of a bald area, so a series of surgeries scheduled three to four months apart is usually required.
The patient may be completely awake during the
procedure with just a local anesthetic drug applied
to numb the areas of the scalp. Some patients may
be given a drug to help them relax or may be given an
anesthetic drug that puts them to sleep.
The most common transplant procedure uses a
thin strip of hair and scalp from the back of the
head. This strip is cut into smaller clumps of five or
six hairs. Tiny cuts are made in the balding area of the
scalp and a clump is implanted into each slit. The
doctor performing the surgery will attempt to recreate
a natural looking hairline along the forehead.
Minigrafts, micrografts, or implants of single hair
follicles can be used to fill in between larger implant
sites and can provide a more natural-looking hairline.
The implants will also be arranged so that thick and
thin hairs are interspersed and the hair will grow in the
same direction.
Another type of hair replacement surgery is
called scalp reduction. This involves removing some
of the skin from the hairless area and ‘‘stretching’’
some of the nearby hair-covered scalp over the cutaway area.
Health insurance will not pay for hair transplants
that are done for cosmetic reasons. Insurance may pay
for hair replacement surgery to correct hair loss due to
accident, burn, or disease.
1667

Hair transplantation

Resources

Hair transplantation
The most common hair transplant procedure involves taking small strips of scalp containing hair follicles from the donor area,
usually at the sides or back of the head. These strips are then divided into several hundred smaller grafts. The surgeon relocates
these grafts containing skin, follicle, and hair to tiny holes in the balding area by using microsurgical instruments or lasers.
(Illustration by Electronic Illustrators Group.)

It is important to be realistic about what the final
result of a hair transplant will look like. This procedure does not create new hair, it simply redistributes
the hair that the patient still has. Some research has
been conducted where chest hair has been transplanted to the balding scalp, but this procedure is not
widely practiced.

Preparation
It is important to find a respected, well-established, experienced surgeon and discuss the expected
results prior to the surgery. The patient may need
blood tests to check for bleeding or clotting problems
and may be asked not to take aspirin products before
the surgery. The type of anesthesia used will depend
on how extensive the surgery will be and where it will
be performed. The patient may be awake during the
procedure, but may be given medication to help
them relax. A local anesthetic drug which numbs the
area will be applied or injected into the skin at the
surgery sites.

Aftercare
The area may need to be bandaged overnight. The
patient can return to normal activities; however, strenuous activities should be avoided in the first few days
after the surgery. On rare occasions, the implants can
be ‘‘ejected’’ from the scalp during vigorous exercise.
There may be some swelling, bruising, headache, and
discomfort around the graft areas and around the
eyes. These symptoms can usually be controlled with
a mild pain reliever like aspirin. Scabs may form at the
graft sites and should not be scraped off. There may be
some numbness at the sites, but it will diminish within
two to three months.
1668

KEY TERMS
Anesthetic agents—Medication or drugs that can
be injected with a needle or rubbed onto and area
to make it numb before a surgical procedure.
Anesthesia drugs may also be given by mouth,
breathed in as a gas, or injected into a vein or
muscle to make a patient relaxed or unconscious.
Hair follicle—A tube-like indentation in the skin
from which a single hair grows.
Minigraft or micrograft—Transplantation of a
small number of hair follicles, as few as one to
three hairs, into a transplant site.
Transplantation—Surgically cutting out hair follicles and replanting them in a different spot on the
head.

Risks
Although there are rare cases of infection or scarring, the major risk is probably that the grafted area
does not look the way the patient expected it to look.

Normal results
The transplanted hair will fall out within a few
weeks, however, new hair will start to grow in the graft
sites within about three months. A normal rate of hair
growth is about 0.25–0.5 in (6–13 mm) per month.

Abnormal results
Major complications as a result of hair transplantation are extremely rare. Occasionally, a patient may
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

American Academy of Cosmetic Surgery. 401 N. Michigan
Ave., Chicago, IL 60611-4267. (313) 527-6713.
<http://www.cosmeticsurgeryonline.com>.
American Academy of Facial Plastic and Reconstructive
Surgery. 1110 Vermont Avenue NW, Suite 220,
Washington, DC 20005. (800) 332-3223.
OTHER

‘‘Hair Transplant.’’ Ienhance. <http://
www.ienhance.com>.
‘‘Transplants; Flap Surgery; and The Perfect Candidate.’’
Transplant Network. <http://
www.hair-transplants.net>.

Altha Roberts Edgren

which mature in the bone marrow. However, extremely rare variants of HCL have been discovered
developing from T-lymphocytes, which mature in the
thymus.
When hairy cell leukemia develops, the white
blood cells become abnormal both in the way they
appear (by acquiring hairy projections) and in the
way they act (by proliferating without the normal
control mechanisms). Further, the cells tend to accumulate in the spleen, causing it to become enlarged.
The cells may also collect in the bone marrow and
prevent it from producing normal blood cells. As a
result, there may not be enough normal white blood
cells in the blood to fight infection.
The median age at which people develop HCL is
52 years. Though it occurs in all ages, HCL more
commonly develops in the older population. Men are
four times more likely to develop HCL than women.
There have been reports of familial aggregation of
disease, with higher occurrences in Ashkenazi Jewish
men. A potential genetic link is undergoing further
investigation.

Hairy cell leukemia
Definition
Hairy cell leukemia is a disease in which a type
of white blood cell called the lymphocyte, present in
the blood and bone marrow, becomes malignant and
proliferates. It is called hairy cell leukemia because
the cells have tiny hair-like projections when viewed
under the microscope.

Description

Causes and symptoms
The cause of hairy cell leukemia is not specifically
known. However, exposure to radiation is a known
cause of leukemia in general. Familial involvement
is another theory, suggesting that there is a genetic
component associated with this disease.
HCL is a chronic (slowly progressing) disease, and
the patients may not show any symptoms for many
years. As the disease advances, the patients may suffer
from one or more of the following symptoms:

Hairy cell leukemia (HCL) is a rare cancer. It was
first described in 1958 as leukemic reticuloendotheliosis, erroneously referring to a red blood cell
because researchers were unsure of the cell of origin.
It became more easily identifiable in the 1970s. There
are approximately 600 new cases diagnosed every year
in the United States, making up about 2% of the adult
cases of leukemia each year.



weakness



fatigue



recurrent infections



fever



anemia



bruising

HCL is found in cells located in the blood. There
are three types of cells found in the blood: the red
blood cells that carry oxygen to all the parts of the
body; the white blood cells that are responsible for
fighting infection and protecting the body from
diseases; and the platelets that help in the clotting of
blood. Hairy cell leukemia affects a type of white
blood cell called the lymphocyte. Lymphocytes are
made in the bone marrow, spleen, lymph nodes, and
other organs. It specifically affects B-lymphocytes,



pain or discomfort in the abdominal area



weight loss (uncommon)



night sweats (uncommon)

GALE ENCYCLOPEDIA OF MEDICINE

Pain and discomfort are caused by an enlarged
spleen, which results from the accumulation of the
abnormal hairy cells in the spleen. Blood tests may
show abnormal counts of all the different types of
cells. This happens because the cancerous cells invade
the bone marrow as well and prevent it from
1669

Hairy cell leukemia

have problems with delayed healing, infection, scarring, or rejection of the graft; but this is uncommon.

Hairy cell leukemia

producing normal blood cells. Because of the low
white cell count in the blood, the patient may have
frequent infections. Fever often accompanies the
infections. The patient is most susceptible to bacterial
infections, but infections of any kind are the major
cause of death. The low red cell count may cause
anemia, fatigue, and weakness, and the low platelet
count may cause the person to bruise and bleed easily.

Diagnosis
When a patient suffers from the above symptoms,
the doctor will palpate the abdomen and may order
scans to see if the spleen is enlarged (splenomegaly).
An enlarged spleen is present in 80% of patients. An
enlarged liver is less common, but can occur.
If the spleen is enlarged, the doctor may order
several blood tests. In these tests, the total numbers
of each of the different types of blood cells (CBC) are
reported. Sixty to eighty percent of patients suffer
from pancytopenia, which is a dramatic reduction in
the number of red blood cells, white blood cells, and
platelets circulating in the blood.
If the blood tests are abnormal, the doctor may
order a bone marrow aspiration and biopsy. In order
to establish a diagnosis, hairy cells must be present in
the bone marrow.

Treatment
When physicians perform blood tests, they will
determine the level of hemoglobin (the oxygentransporting molecule of red blood cells). Serum
hemoglobin levels and the size of the spleen, which
can be measured on exam and by using an x ray, are
proposed criteria for determining the stage of HCL.
The following are the three proposed stages and their
criteria:


Stage I: Hemoglobin greater than 12 g/dL (1 g =
approximately 0.02 pint and 1 dL = approximately
0.33 ounce) and spleen less than or equal to 10 cm
(3.9 inches).



Stage II: Hemoglobin between 8.5 and 12 g/dL and
spleen greater than 10 cm (3.9 inches).



Stage III: Hemoglobin less than 8.5 g/dL and spleen
greater than 10 cm (3.9 inches).

Since there is generally no accepted staging system, another method for evaluating the progression of
HCL is to group patients into two categories:
untreated HCL and progressive HCL, in which hairy
cells are present after therapy has been administered.
1670

A magnified image of white blood cells with ‘‘hairy’’
projections. (Photograph by M. Abbey. Photo Researchers, Inc.
Reproduced by permission.)

Some people with hairy cell leukemia have very
few or no symptoms at all, and it is reasonable to
expect that 10% of patients may not need any treatment. However, if the patient is symptomatic and
needs intervention, HCL is especially responsive to
treatment.
There are three main courses of treatment: chemotherapy, splenectomy (surgical removal of the
spleen), and immunotherapy. Once a patient meets
treatment criteria, purine analogues, particularly the
drugs, pentostatin and cladribine, are the first-line
therapy. Pentostatin is administered at 5mg/m2 for
two days every other week until total remission is
achieved. Patients may experience side effects such as
fever, nausea, vomiting, photosensitivity, and keratoconjuctivitis. However, follow-up studies estimate a
relapse-free survival rate at 76%. Cladribine (2-CdA)
taken at 0.1mg/kg/day for seven days also has an
impressive response. Eighty-six percent of patients
experience complete remission after treatment, while
16% experience partial remission. Fever is the principal side effect of 2-CdA.
Biological therapy or immunotherapy, where the
body’s own immune cells are used to fight cancer, is
also being investigated in clinical trials for hairy
cell leukemia. A substance called interferon that is
produced by the white blood cells of the body was
the first systemic treatment that showed consistent
results in fighting HCL. The FDA approved interferon-alpha (INF-alpha) to fight HCL. The mechanism by which INF-alpha works is not clearly
understood. However, it is known that interferon
stimulates the body’s natural killer cells that are
suppressed during HCL. The standard dosage is
2 MU/m2 three times a week for 12 months. Side
GALE ENCYCLOPEDIA OF MEDICINE

Anemia—A condition in which there is low iron in
the blood due to a deficiency of red blood cells.
Bone marrow—The spongy tissue inside the large
bones in the body that is responsible for making the
red blood cells, white blood cells, and platelets.
Bone marrow aspiration and biopsy—A procedure
in which a needle is inserted into the large bones of
the hip or spine and a small piece of marrow is
removed for microscopic examination.
Immunotherapy—A mode of cancer treatment in
which the immune system is stimulated to fight the
cancer.
Leukemia—A disease in which the cells that constitute the blood become cancerous or abnormal.
Lymph nodes—Oval-shaped organs that are the
size of peas, located throughout the body, and
contain clusters of cells called lymphocytes. They
filter out and destroy the bacteria, foreign particles,
and cancerous cells from the blood.
Malignant—Cells that have the ability to invade
locally, cause destruction of surrounding tissue,
and travel to other sites in the body.
Keratoconjunctivitis—Inflammation of the conjunctiva and cornea of the eye.
Spleen—An organ that lies next to the stomach. Its
function is to remove the worn-out blood cells and
foreign materials from the blood stream.
Splenectomy—A surgical procedure that involves
the surgical removal of the spleen.

effects include fever, myalgia, malaise, rashes, and
gastrointestinal complaints.
If the spleen is enlarged, it may be removed in a
surgical procedure known as splenectomy. This
usually causes a remission of the disease. However,
50% of patients that undergo splenectomy require
some type of systemic treatment such as chemotherapy
or immunotherapy. Splenectomy is not the most
widely used course of treatment as it was many years
ago. Although the spleen is not an indispensable
organ, it is responsible for helping the body fight
infection. Therefore, other therapies are preferred in
order to salvage the spleen and its functions.
Most patients have excellent prognosis and can
expect to live 10 years or longer. The disease may
remain silent for years with treatment. Continual
GALE ENCYCLOPEDIA OF MEDICINE

follow-up is necessary to monitor the patient for
relapse and determine true cure rates.

Alternative treatment
Many individuals choose to supplement traditional therapy with complementary methods. Often,
these methods improve the tolerance of side effects
and symptoms as well as enrich the quality of life.
The American Cancer Society recommends that
patients talk to their doctor to ensure that the methods
they are using are safely supplementing traditional
therapy. Some complementary treatments include the
following:



yoga



meditation



religious practices and prayer



music therapy



art therapy



massage therapy



aromatherapy

Prevention
Since the cause for the disease is unknown and
there are no specific risk factors, there is no known
prevention.
Resources
BOOKS

Bast, Robert C. Cancer Medicine. Lewiston, NY:B.C.
Decker Inc., 2000.
Haskell, Charles M. Cancer Treatment. 5th ed. Philadephia:
W.B. Saunders Company, 2001.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, N.E. Atlanta,
Georgia 30329. (800) 227-2345. <http://
www.cancer.org>.
Cancer Research Institute (National Headquarters). 681
Fifth Avenue, New York, N.Y. 10022. (800) 992-2623.
<http://www.cancerresearch.org>.
Hairy Cell Leukemia Research Foundation. 2345 County
Farm Lane, Schaumburg, IL 60194. (800) 693-6173.
Leukemia Society of America, Inc. 600 Third Ave, New
York, NY 10016. (800) 955-4572.
National Cancer Institute. 9000 Rockville Pike, Building 31,
Room 10A16, Bethesda, Maryland, 20892. (800)
422-6237. <http://wwwicic.nci.nih.gov>.
Oncolink. University of Pennsylvania Cancer Center.
<http://cancer.med.upenn.edu>.
1671

Hairy cell leukemia

KEY TERMS

Hallucinations

OTHER

‘‘Coping With Side Effects.’’ National Cancer Institute. July
2, 2001. <http://cancernet.nci.nih.gov/chemotherapy/
chemoside.html>.
NCI/PDQ Patient Statement, ‘‘Hairy cell leukemia.’’
National Cancer Institute, 2001.

Lata Cherath, PhD
Sally C. McFarlane-Parrott

Halitosis see Bad breath

Hallucinations
Definition
Hallucinations are false or distorted sensory
experiences that appear to be real perceptions. These
sensory impressions are generated by the mind rather
than by any external stimuli, and may be seen, heard,
felt, and even smelled or tasted.

Ecstasy tablets. (Corbis. Reproduced by permission)

(3,4,5-trimethoxyphenethylamine, or peyote), and
psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine, or mushrooms) trigger hallucinations. Other
drugs such as marijuana and PCP have hallucinatory
effects. Certain prescription medications may also
cause hallucinations. In addition, drug withdrawal
may induce tactile and visual hallucinations; as in an
alcoholic suffering from delirium tremens (DTs).

Description
A hallucination occurs when environmental, emotional, or physical factors such as stress, medication,
extreme fatigue, or mental illness cause the mechanism
within the brain that helps to distinguish conscious
perceptions from internal, memory-based perceptions
to misfire. As a result, hallucinations occur during
periods of consciousness. They can appear in the
form of visions, voices or sounds, tactile feelings
(known as haptic hallucinations), smells, or tastes.
Patients suffering from dementia and psychotic
disorders such as schizophrenia frequently experience
hallucinations. Hallucinations can also occur in
patients who are not mentally ill as a result of stress
overload or exhaustion, or may be intentionally
induced through the use of drugs, meditation, or sensory
deprivation. A 1996 report, published in the British
Journal of Psychiatry, noted that 37% of 4,972 people
surveyed experienced hypnagogic hallucinations (hallucinations that occur as a person is falling to sleep).
Hypnopomic hallucinations (hallucinations that occur
just upon waking) were reported by 12% of the sample.

Causes and symptoms



Stress. Prolonged or extreme stress can impede
thought processes and trigger hallucinations.



Sleep deprivation and/or exhaustion. Physical and
emotional exhaustion can induce hallucinations by
blurring the line between sleep and wakefulness.



Meditation and/or sensory deprivation. When the
brain lacks external stimulation to form perceptions,
it may compensate by referencing the memory and
form hallucinatory perceptions. This condition is
commonly found in blind and deaf individuals.



Electrical or neurochemical activity in the brain. A
hallucinatory sensation—usually involving touch—
called an aura, often appears before, and gives
warning of, a migraine. Also, auras involving smell
and touch (tactile) are known to warn of the onset of
an epileptic attack.



Mental illness. Up to 75% of schizophrenic patients
admitted for treatment report hallucinations.



Brain damage or disease. Lesions or injuries to the
brain may alter brain function and produce
hallucinations.

Common causes of hallucinations include:


Drugs. Hallucinogenics such as ecstasy (3,4-methylenedioxymethamphetamine, or MDMA), LSD
(lysergic acid diethylamide, or acid), mescaline

1672

GALE ENCYCLOPEDIA OF MEDICINE

Aside from hypnogogic and hypnopompic hallucinations, more than one event suggests a person
should seek evaluation. A general physician, psychologist, or psychiatrist will try to rule out possible
organic, environmental, or psychological causes
through a detailed medical examination and social
history. If a psychological cause such as schizophrenia
is suspected, a psychologist will typically conduct an
interview with the patient and his family and administer one of several clinical inventories, or tests, to
evaluate the mental status of the patient.
Occasionally, people who are in good mental
health will experience a hallucination. If hallucinations are infrequent and transitory, and can be
accounted for by short-term environmental factors
such as sleep deprivation or meditation, no treatment
may be necessary. However, if hallucinations are hampering an individual’s ability to function, a general
physician, psychologist, or psychiatrist should be
consulted to pinpoint their source and recommend a
treatment plan.

KEY TERMS
Aura—A subjective sensation or motor phenomenon that precedes and indicates the onset of a
neurological episode, such as a migraine or an
epileptic seizure.
Hypnogogic hallucination—A hallucination, such
as the sensation of falling, that occurs at the onset of
sleep.
Hypnopompic hallucination—A hallucination that
occurs as a person is waking from sleep.
Sensory deprivation—A situation where an individual finds himself in an environment without sensory
cues. Also, (used here) the act of shutting one’s
senses off to outside sensory stimuli to achieve
hallucinatory experiences and/or to observe the
psychological results.

Hallucinogen see Lysergic acid
diethylamide
Hallux valgus see Bunion

Treatment
Hallucinations that are symptomatic of a mental illness such as schizophrenia should be treated
by a psychologist or psychiatrist. Antipsychotic
medication such as thioridazine (Mellaril), haloperidol (Haldol), chlorpromazine (Thorazine), clozapine (Clozaril), or risperidone (Risperdal) may be
prescribed.

Haloperidol see Antipsychotic drugs

Hammertoe
Definition

Prognosis
In many cases, chronic hallucinations caused by
schizophrenia or some other mental illness can be
controlled by medication. If hallucinations persist,
psychosocial therapy can be helpful in teaching the
patient the coping skills to deal with them.
Hallucinations due to sleep deprivation or extreme
stress generally stop after the cause is removed.
Resources
ORGANIZATIONS

American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.

Paula Anne Ford-Martin
GALE ENCYCLOPEDIA OF MEDICINE

Hammertoe is a condition in which the toe is bent
in a claw-like position. It can be present in more than
one toe but is most common in the second toe.

Description
Hammertoe is described as a deformity in which
the toes bend downward with the toe joint usually
enlarged. Over time, the joint enlarges and stiffens as
it rubs against shoes. Other foot structures involved
include the overlying skin and blood vessels and nerves
connected to the involved toes.

Causes and symptoms
The shortening of tendons responsible for the
control and movement of the affected toe or toes
cause hammertoe. Top portions of the toes become
callused from the friction produced against the inside
of shoes. This common foot problem often results
1673

Hammertoe

Diagnosis

Hand-foot-and-mouth disease

from improper fit of footwear. This is especially the
case with high-heeled shoes placing pressure on the
front part of the foot that compresses the smaller
toes tightly together. The condition frequently stems
from muscle imbalance, and usually leaves the affected
individual with impaired balance.

Diagnosis
A thorough medical history and physical exam by
a physician is always necessary for the proper diagnosis of hammertoe and other foot conditions. Because
the condition involves bony deformity, x rays can help
to confirm the diagnosis.

Treatment
Conservative
Wearing proper footwear and stockings with
plenty of room in the toe region can provide treatment
for hammertoe. Stretching exercises may be helpful in
lengthening the excessively tight tendons.

Hammertoe most commonly affects the second toe which, as
shown, often develops a corn over the deformity. (Photograph
by Dr. H.C. Robinson, Custom Medical Stock Photo. Reproduced
by permission.)

Surgery
In advanced cases, where conservative treatment
is unsuccessful, surgery may be recommended. The
tendons that attach to the involved toes are located
and an incision is made to free the connective tissue to
the foot bones. Additional incisions are made so the
toes no longer bend in a downward fashion. The middle joints of the affected toes are connected together
permanently with surgical hardware such as pins and
wire sutures. The incision is then closed with fine
sutures. These sutures are removed approximately
seven to ten days after surgery.

age. Feet should always be measured before buying
shoes. The upper part of the shoes should be made of
a soft, flexible material to match the shape of the foot.
Shoes made of leather can reduce the possibility of skin
irritations. Soles should provide solid footing and not
be slippery. Thick soles lessen pressure when walking
on hard surfaces. Low-heeled shoes are more comfortable, safer, and less damaging than high-heeled shoes.
Resources
ORGANIZATIONS

Alternative treatment
Various soft tissue and joint treatments offered by
chiropractic and massage therapy may be useful to
decrease the tightness of the affected structures.

American Orthopedic Foot and Ankle Society. 222 South
Prospect, Park Ridge, IL 60068.
American Podiatry Medical Association. 9312 Old
Georgetown Road, Bethesda, MD 20814.

Jeffrey P. Larson, RPT

Prognosis
If detected early, hammertoe can be treated nonsurgically. If surgery becomes necessary, surgical risks
are minimal with the overall outcome providing good
results.

Hand-foot-and-mouth disease
Definition

Prevention
Wearing comfortable shoes that fit well can prevent many foot ailments. Foot width may increase with
1674

Hand-foot-and-mouth disease is an infection of
young children in which characteristic fluid-filled blisters appear on the hands, feet, and inside the mouth.
GALE ENCYCLOPEDIA OF MEDICINE

Hand-foot-and-mouth disease

Description
Coxsackie viruses belong to a family of viruses
called enteroviruses. These viruses live in the gastrointestinal tract, and are therefore present in feces. They
can be spread easily from one person to another when
poor hygiene allows the virus within the feces to be
passed from person to person. After exposure to the
virus, development of symptoms takes only four to six
days. Hand-foot-and-mouth disease can occur yearround, although the largest number of cases are in
summer and fall months.
An outbreak of hand-foot-and-mouth disease
occurred in Singapore in 2000, with more than 1,000
diagnosed cases, all in children, resulting in four
deaths. A smaller outbreak occurred in Malaysia in
2000. In 1998, a serious outbreak of enterovirus 71 in
Taiwan resulted in more than one million cases of
hand-foot-and-mouth disease. Of these, there were
405 severe cases and 78 deaths, 71 of which were
children younger than five years of age.
Hand-foot-and-mouth should not be confused
with foot and mouth disease, which infects cattle but
is extremely rare in humans. An outbreak of foot and
mouth disease swept through Great Britain and into
other parts of Europe and South America in 2001.

A child’s foot with pustules on toes, indicating hand-footmouth disease. (Custom Medical Stock Photo. Reproduced by
permission.)

within the vesicles contains large quantities of the
causative viruses. Extra care should be taken to
avoid contact with this fluid.

Diagnosis
Diagnosis is made by most practitioners solely
on the basis of the unique appearance of blisters of
the mouth, hands, and feet, in a child not appearing
very ill.

Causes and symptoms
Hand-foot-and-mouth disease is very common
among young children, and often occurs in clusters
of children who are in daycare together. It is spread
when poor hand-washing after a diaper change or
contact with saliva (drool) allows the virus to be
passed from one child to another.
Within about four to six days of acquiring the
virus, an infected child may develop a relatively lowgrade fever, ranging from 99–102  F (37.2–38.9  C).
Other symptoms include fatigue, loss of energy,
decreased appetite, and a sore sensation in the mouth
that may interfere with feeding. After one to two days,
fluid-filled bumps (vesicles) appear on the inside of the
mouth, along the surface of the tongue, on the roof of
the mouth, and on the insides of the cheeks. These are
tiny blisters, about 3–7 mm in diameter. Eventually,
they may appear on the palms of the hands and on the
soles of the feet. Occasionally, these vesicles may occur
in the diaper region.
The vesicles in the mouth cause the majority of
discomfort, and the child may refuse to eat or drink
due to pain. This phase usually lasts for an average of a
week. As long as the bumps have clear fluid within
them, the disease is at its most contagious. The fluid
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
There are no treatments available to cure or
decrease the duration of the disease. Medications like
acetaminophen or ibuprofen may be helpful for
decreasing pain, and allowing the child to eat and
drink. It is important to try to encourage the child to
take in adequate amounts of fluids, in the form of ice
chips or popsicles if other foods or liquids are too
uncomfortable.

Alternative treatment
There are no effective alternative treatments for
hand-foot-and-mouth disease.

Prognosis
The prognosis for a child with hand-foot-and-mouth
disease is excellent. The child is usually completely better
within about a week of the start of the illness.

Prevention
Prevention involves careful attention to hygiene.
Thorough, consistent hand-washing practices, and
1675

Hantavirus infections

KEY TERMS
Enteroviruses—Viruses which live in the gastrointestinal tract. Coxsackie viruses, viruses that
cause hand-foot-mouth disease, are an enterovirus.
Vesicle—A bump on the skin filled with fluid.

discouraging the sharing of clothes, towels, and
stuffed toys are all helpful. Virus continues to be
passed in the feces for several weeks after infection,
so good hygiene should be practiced long after all signs
of infection have passed.
Resources

of virus causes a slightly different form of illness in its
human hosts:


Hantaan virus is carried by the striped field mouse,
and exists in Korea, China, Eastern Russia, and the
Balkans. Hantaan virus causes a severe form of
hemorrhagic fever with renal syndrome (HFRS).



Puumula virus is carried by bank voles, and exists in
Scandinavia, western Russia, and Europe. Puumula
virus causes a milder form of HFRS, usually termed
nephropathia epidemica.



Seoul virus is carried by a type of rat called the
Norway rat, and exists worldwide, but causes disease
almost exclusively in Asia. Seoul virus causes a form
of HFRS that is slightly milder than that caused by
Hantaan virus, but results in liver complications.



Prospect Hill virus is carried by meadow voles and
exists in the United States, but has not been found to
cause human disease.



Sin Nombre virus, the most predominant strain in
the United States, is carried by the deer mouse. This
virus was responsible for severe cases of HPS that
occurred in the Southwestern United States in 1993.



Black Creek Canal virus has been found in Florida.
It is predominantly carried by cotton rats.



New York virus strain has been documented in New
York State. The vectors for this virus seem to be deer
mice and white-footed mice.



Bayou virus has been reported in Louisiana and
Texas and is carried by the marsh rice rat.



Blue River virus has been found in Indiana and
Oklahoma and seems to be associated with the
white-footed mouse.



Monongahela virus, discovered in 2000, has been
found in Pennsylvania and is transmitted by the
white-footed mouse.

BOOKS

Morag, Abraham, and Pearay L. Ogra. ‘‘Viral Infections.’’
In Nelson Textbook of Pediatrics. edited by Richard
Behrman, 16th ed. Philadelphia: W.B. Saunders Co.,
2000.
PERIODICALS

‘‘New Tricks for an Old Enterovirus.’’ Infectious Disease
Alert (December 15, 1999): 45.

Rosalyn Carson-DeWitt, MD
Ken R. Wells

Hand-Schüller-Christian syndrome see
Histiocytosis X
Hansen’s disease see Leprosy

Hantavirus infections
Definition
Hantavirus infection is caused by a group
of viruses that can infect humans with two serious
illnesses: hemorrhagic fever with renal syndrome
(HFRS), and Hantavirus pulmonary syndrome (HPS).

Description
Hantaviruses are found without causing symptoms within various species of rodents and are passed
to humans by exposure to the urine, feces, or saliva of
those infected rodents. Ten different hantaviruses
have been identified as important in humans. Each is
found in specific geographic regions, and therefore is
spread by different rodent carriers. Further, each type
1676

Causes and symptoms
Hemorrhagic fever with renal syndrome (HFRS)
Hantaviruses that produce forms of hemorrhagic
fever with renal syndrome (HFRS) cause a classic
group of symptoms, including fever, malfunction of
the kidneys, and low platelet count. Because platelets
are blood cells important in proper clotting, low numbers of circulating platelets can result in spontaneous
bleeding, or hemorrhage.
Patients with HFRS have pain in the head, abdomen, and lower back, and may report bloodshot eyes
and blurry vision. Tiny pinpoint hemorrhages, called
petechiae, may appear on the upper body and the soft
GALE ENCYCLOPEDIA OF MEDICINE

After about five days, the patient may have a
sudden drop in blood pressure; often it drops low
enough to cause the clinical syndrome called shock.
Shock is a state in which blood circulation throughout
the body is insufficient to deliver proper quantities of
oxygen. Lengthy shock can result in permanent
damage to the body’s organs, particularly the brain,
which is very sensitive to oxygen deprivation.
Around day eight of HFRS, kidney involvement
results in multiple derangements of the body chemistry. Simultaneously, the hemorrhagic features of the
illness begin to cause spontaneous bleeding, as demonstrated by bloody urine, bloody vomit, and in very
serious cases, brain hemorrhages with resulting
changes in consciousness.
Day eleven often brings further chemical derangements, with associated confusion, hallucinations, seizures, and lung complications. Those who survive this
final phase usually begin to turn the corner toward
recovery at this time, although recovery takes approximately six weeks.
Hantavirus pulmonary syndrome (HPS)
Hantavirus pulmonary syndrome (HPS) develops
in four stages. They are:


The incubation period. This lasts from one to five
weeks from exposure. Here, the patient may exhibit
no symptoms.



The prodrome, or warning signs, stage. Symptoms
begin with a fever, muscle aches, headache, dizziness,
and abdominal pain and upset. Sometimes there is
vomiting and diarrhea.



The cardiopulmonary stage. The patient slips into
this stage rapidly, sometimes within a day or two of
initial symptoms; sometimes as long as 10 days later.
There is a drop in blood pressure, shock, and leaking
of the blood vessels of the lungs, which results in fluid
accumulation in the lungs, and subsequent shortness
of breath. The fluid accumulation can be so rapid and
so severe as to put the patient in respiratory failure
within only a few hours. Some patients experience
severe abdominal tenderness.



The convalescent stage. If the patient survives the
respiratory complications of the previous stage,
there is a rapid recovery, usually within a day or
two. However, abnormal liver and lung functioning
may persist for six months.

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Serologic techniques help diagnose a hantavirus
infection. The patient’s blood is drawn, and the
ELISA (enzyme-linked immunosorbent assay) is
done in a laboratory to identify the presence of specific
immune substances (antibodies)—substances which
an individual’s body would only produce in response
to the hantavirus.
It is very difficult to demonstrate the actual virus
in human tissue, or to grow cultures of the virus within
the laboratory, so the majority of diagnostic tests use
indirect means to demonstrate the presence of the
virus.

Treatment
Treatment of hantavirus infections is primarily
supportive, because there are no agents available to
kill the viruses and interrupt the infection. Broadspectrum antibiotics are given until the diagnosis is
confirmed. Supportive care consists of providing
treatment in response to the patient’s symptoms.
Because both HFRS and HPS progress so rapidly,
patients must be closely monitored, so that treatment
may be started at the first sign of a particular problem.
Low blood pressure is treated with medications.
Blood transfusions are given for both hemorrhage
and shock states. Hemodialysis is used in kidney failure. (Hemodialysis involves mechanically cleansing
the blood outside of the body, to replace the kidney’s
normal function of removing various toxins form the
blood.) Rapid respiratory assistance is critical, often
requiring intubation.
The anti-viral agent ribavirin has been approved
for use in early treatment of hantavirus infections.

Prognosis
The diseases caused by hantaviruses are extraordinarily lethal. About 6–15% of people who contract HFRS have died. Almost half of all people
who contract HPS will die. This gives HPS one of the
highest fatality rates of any acute viral disease. It is
essential that people living in areas where the hantaviruses exist seek quick medical treatment should
they begin to develop an illness that might be due to
a hantavirus.

Prevention
There are no immunizations currently available
against any of the hantaviruses. In 2003, developments
in genetic science were helping researchers work on a
1677

Hantavirus infections

palate in the mouth. The patient’s face, chest, abdomen, and back often appear flushed and red, as if
sunburned.

Haptoglobin test



Airing out all sealed outbuildings or cabins 30 minutes before cleaning for the season.



When camping, avoiding sleeping on the bare
ground. It is advised to sleep on a cot or in a tent
with a floor.

KEY TERMS
Hemodialysis—A method of mechanically cleansing the blood outside of the body, in order to
remove various substances that would normally
be cleared by the kidneys. Hemodialysis is used
when an individual is in relative, or complete, kidney failure.
Hemorrhagic—A condition resulting in massive,
difficult-to-control bleeding.
Petechiae—Pinpoint size red spots caused by
hemorrhaging under the skin.
Platelets—Circulating blood cells that are crucial
to the mechanism of clotting.
Prodrome—Early symptoms or warning signs
Pulmonary—Referring to the lungs.
Renal—Referring to the kidneys.
Shock—Shock is a state in which blood circulation
is insufficient to deliver adequate oxygen to vital
organs.

possible vaccination and therapy for several versions
of hantavirus, including the Sin Nombre virus that
causes HPS. With further work, a gene-based vaccine
could become available in the future. However, the
only known forms of hantavirus prevention involve
rodent control within the community and within individual households. The following is a list of preventive
measures:


Avoiding areas known to be infested by rodents is
essential.



Keeping a clean home and keeping food in rodentproof containers.



Disposing of garbage and emptying pet food dishes
at night.



Setting rodent traps around baseboards and in tight
places. Disposing of dead animals with gloves and
disinfecting the area with bleach.



Using rodenticide as necessary.



Sealing any entry holes 0.25 inch wide or wider
around foundations with screen, cement, or metal
flashing.



Clearing brush and junk from house foundations.



Putting metal flashing around house foundations.



Elevating hay, woodpiles, and refuse containers.

1678

Resources
BOOKS

Harper, David R., and Andrea S. Meyer. Of Mice, Men, and
Microbes: Hantavirus. San Diego: Academic Press, 1999.
PERIODICALS

‘‘DNA Vaccine Protects Against Hantavirus Pulmonary
Syndrome.’’ Heart Disease Weekly November 2,
2003: 31.
Jones, Amy. ‘‘Setting a Trap for Hantavirus.’’ Nursing
September 2000: 20.
Monroe, Martha C., Sergey P. Morzunov, Angela M.
Johnson, Michael De. Bowen, et al. ‘‘Genetic Diversity
and Distribution of Peromyscus-Borne Hantaviruses
in North America.’’ Nursing January-February 1999:
75–86.
Naughton, Laurie. ‘‘Hantavirus Infection in the United
States: Are We Prepared?’’ Physician Assistant May
2000: 33.
Rhodes III, Luther V., Cinnia Huang, Angela J. Sanchez,
Stuart T. Nichol, et al. ‘‘Hantavirus Pulmonary
Syndrome Associated with Monongahela Virus,
Pennsylvania.’’ Emerging Infectious Diseases
November 2000: 616.
Van Bevern, Pamela A. ‘‘Hantavirus Pulmonary
Syndrome.’’ Clinician Reviews July 2000: 108.

Janie F. Franz
Teresa G. Odle

Haptoglobin test
Definition
This test is done to help evaluate a person for
hemolytic anemia.

Purpose
Haptoglobin is a blood protein made by the liver.
The haptoglobin levels decrease in hemolytic anemia.
Hemolytic anemias include a variety of conditions that
result in hemolyzed, or burst, red blood cells.
Decreased values can also indicate a slower type
of red cell destruction unrelated to anemia. For example, destruction can be caused by mechanical heart
GALE ENCYCLOPEDIA OF MEDICINE

Haptoglobin is known as an acute phase reactant.
Its level increases during acute conditions such as
infection, injury, tissue destruction, some cancers,
burns, surgery, or trauma. Its purpose is to remove
damaged cells and debris and rescue important material such as iron. Haptoglobin levels can be used to
monitor the course of these conditions.

Description
Hemoglobin is the protein in the red blood cell
that carries oxygen throughout the body. Iron is an
essential part of hemoglobin; without iron, hemoglobin can not function. Haptoglobin’s main role is to
save iron by attaching itself to any hemoglobin
released from a red cell.
When red blood cells are destroyed, the hemoglobin is released. Haptoglobin is always present in
the blood waiting to bind to released hemoglobin.
White blood cells (called macrophages) bring the
haptoglobin-hemoglobin complex to the liver, where
the haptoglobin and hemoglobin are separated and
the iron is recycled.
In hemolytic anemia, so many red cells are destroyed
that most of the available haptoglobin is needed to
bind the released hemoglobin. The more severe the
hemolysis, the less haptoglobin remains in the blood.
Haptoglobin is measured in several different
ways. One way is called rate nephelometry. A person’s
serum is mixed with a substance that will bind to
haptoglobin. The amount of bound haptoglobin is
measured using a rate nephelometer, which measures
the amount of light scattered by the bound haptoglobin. Another way of measuring haptoglobin is to measure it according to how much hemoglobin it can bind.

Preparation
This test requires 5 mL of blood. The person being
tested should avoid taking oral contraceptives or
androgens before this test. A healthcare worker ties a
tourniquet on the person’s upper arm, locates a vein in
the inner elbow region, and inserts a needle into that
vein. Vacuum action draws the blood through the
needle into an attached tube. Collection of the sample
takes only a few minutes.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Acute phase reactant—A substance in the blood
that increases as a response to an acute condition
such as infection, injury, tissue destruction, some
cancers, burns, surgery, or trauma.
Haptoglobin—A blood protein made by the liver.
Its main role is to save iron by attaching itself to any
hemoglobin released from a red cell.
Hemoglobin—The protein in the red blood cell that
carries oxygen.
Hemolytic anemia—A variety of conditions that
result in hemolyzed, or burst, red blood cells.

puncture site until the bleeding stops reduces bruising.
Warm packs to the puncture site relieve discomfort.

Normal results
Normal results vary based on the laboratory and
test method used. Haptoglobin is not present in newborns at birth, but develop adult levels by 6 months.

Abnormal results
Decreased haptoglobin levels usually indicates
hemolytic anemia. Other causes of red cell destruction
also decrease haptoglobin: a blood transfusion reaction; mechanical heart valve; abnormally shaped red
cells; or abnormal hemoglobin, such as thalassemia or
sickle cell anemia.
Haptoglobin levels are low in liver disease,
because the liver can not manufacture normal
amounts of haptoglobin. Low levels may also indicate
an inherited lack of haptoglobin, a condition found
particularly in African Americans.
Haptoglobin increases as a reaction to illness,
trauma, or rheumatoid disease. High haptoglobin
values should be followed-up with additional tests.
Drugs can also effect haptoglobin levels.
Normal results vary widely from person to
person. Unless the level is very high or very low,
haptoglobin levels are most valuable when the results
of several tests done on different days are compared.
Nancy J. Nordenson

Hardening of the arteries see Atherosclerosis
Harelip see Cleft lip and palate
1679

Haptoglobin test

valves or abnormal hemoglobin, such as sickle cell
disease or thalassemia.

Hartnup disease

KEY TERMS

Hartnup disease
Definition
Hartnup disease is an inherited nutritional disorder with primary symptoms including a red, scaly
rash and sensitivity to sunlight.

Description
Hartnup disease was first identified in the 1950s in
the Hartnup family in London. A defect in intestines
and kidneys makes it difficult to break down and
absorb protein in the diet. This causes a condition
very similar to pellegra (niacin deficiency). The condition occurs in about one of every 26,000 live births.

Causes and symptoms
Hartnup disease is an in-born error of metabolism, that is, a condition where certain nutrients cannot be digested and absorbed properly. The condition
is passed on genetically in families. It occurs when a
person inherits two recessive genes for the disease, one
from each parent. People with Hartnup disease are not
able to absorb some of the amino acids (the smaller
building blocks that make up proteins) in their intestines. One of the amino acids that is not well absorbed
is tryptophan, which the body uses to make its own
form of niacin.
The majority of people with this disorder do not
show any symptoms. About 10–20% of people with
Hartnup disease do have symptoms. The most prominent symptom is a red, scaly rash that gets worse when
the patient is exposed to sunlight. Headache, fainting,
and diarrhea may also occur. Mental retardation, cerebral ataxia (muscle weakness), and delirium (a confused, agitated, delusional state) are some of the
more serious complications that can occur. Short stature has also been noted in some patients. Although
this is an inherited disease, the development of symptoms depends on a variety of factors including diet,
environment, and other genetic traits controlling
amino acid levels in the body. Symptoms can be
brought on by exposure to sunlight, fever, drugs, or
other stresses. Poor nutrition frequently precedes an
attack of symptoms. The frequency of attacks usually
decreases as the patient gets older.

Diagnosis
The symptoms of this disease suggest a deficiency
of a B vitamin called niacin. A detailed diet history can
1680

Amino acids—Proteins are made up of organic
compounds called amino acids. The human body
uses amino acids to build and repair body tissue.
The body can make some of its own amino acids
from other nutrients in the diet; these are called
non-essential amino acids. Essential amino acids
are those that cannot be made by the body but
must be consumed in the diet. Animal proteins
(like meat, eggs, fish, and milk) provide all of the
amino acids.
Aminoaciduria—A condition confirmed by laboratory tests where high levels of amino acids are
found in the urine.
Pellegra—A condition caused by a dietary deficiency of one of the B vitamins, called niacin.
Tryptophan—An essential amino acid that has to
consumed in the diet because it cannot be manufactured by the body. Tryptophan is converted by
the body to niacin, one of the B vitamins.

be used to assess if there is adequate protein and
vitamins in the diet. The diagnosis of Hartnup disease
is confirmed by a laboratory test of the urine which
will contain an abnormally high amount of amino
acids (aminoaciduria).

Treatment
The vitamin niacin is given as a treatment
for Hartnup disease. The typical dosage ranges from
40–200 mg of nicotinamide (a form of niacin) per day
to prevent pellagra-like symptoms. Some patients may
require dietary supplements of tryptophan.
Eating a healthy, high protein diet can relieve the
symptoms and prevent them from recurring.

Prognosis
The prognosis for a healthy life is good once the
condition has been identified and treated.

Prevention
Hartnup disease is an inherited condition. Parents
may not have the disease themselves, but may pass the
genes responsible for it on to their children. Genetic
testing can be used to identify carriers of the genes.
Symptoms can usually be controlled with a high
GALE ENCYCLOPEDIA OF MEDICINE

by physical therapists to improve many injuries and
disabilities, as the gentleness and adaptability of yoga
make it an excellent rehabilitation program.

Resources

Yoga has been touted for its ability to reduce
problems with such varying conditions as asthma,
backaches, diabetes, constipation, menopause, multiple
sclerosis, varicose veins, and carpal tunnel syndrome.
A vegetarian diet is the dietary goal of yoga, and this
change of lifestyle has been shown to significantly
increase longevity and reduce heart disease.

ORGANIZATIONS

National Organization for Rare Disorders. PO Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.
NIH/National Institute of Diabetes, Digestive and Kidney
Diseases. Building 31, Room 9A04, 31 Center Drive,
Bethesda MD 20892-2560. (301) 496-3583.
OTHER

‘‘Hartnup disorder.’’ OMIM Homepage, Online
Mendelian Inheritance in Man. <http://
www.ncbi.nlm.nih.gov/Omim>.
‘‘Nephrology: Hartnup disease.’’ Medstudents.com.
<http://www.medstudents.com>.

Altha Roberts Edgren

Hashimoto’s disease see Thyroiditis

Yoga as a daily exercise program can improve
fitness, strength, and flexibility. People who practice
yoga correctly every day report that it can promote
high levels of overall health and energy. The mental
component of yoga can clarify and discipline the mind,
and yoga practitioners say its benefits can permeate
all facets of a person’s life and attitude, raising selfesteem and self-understanding.

Description
Origins

Hatha yoga
Definition
Hatha yoga is the most widely practiced form
of yoga in America. It is the branch of yoga which
concentrates on physical health and mental wellbeing. Hatha yoga uses bodily postures (asanas),
breathing techniques (pranayama), and meditation
(dyana) with the goal of bringing about a sound,
healthy body and a clear, peaceful mind. There are
nearly 200 hatha yoga postures, with hundreds of
variations, which work to make the spine supple and
to promote circulation in all the organs, glands, and
tissues. Hatha yoga postures also stretch and align the
body, promoting balance and flexibility.

Purpose
In a celebrated 1990 study, Dr. Dean Ornish’s
Program for Reversing Heart Disease (Random
House), a cardiologist showed that yoga and meditation combined with a low-fat diet and group support
could significantly reduce the blockage of coronary
arteries. Other studies have shown yoga’s benefit in
reducing stress-related problems such as high blood
pressure and cholesterol. Meditation has been
adopted by medical schools and clinics as an effective
stress management technique. Hatha yoga is also used
GALE ENCYCLOPEDIA OF MEDICINE

Yoga was developed in ancient India as far
back as 5,000 years ago; sculptures detailing yoga
positions have been found in India which date back
to 3000 B.C. Yoga is derived from a Sanskrit word
which means ‘‘union.’’ The goal of classical yoga is
to bring self-transcendence, or enlightenment,
through physical, mental and spiritual health. Many
people in the West mistakenly believe yoga to be a
religion, but its teachers point out that it is a system
of living designed to promote health, peace of mind,
and deeper awareness of ourselves. There are several
branches of yoga, each of which is a different path
and philosophy toward self-improvement. Some of
these paths include service to others, pursuit of
wisdom, non-violence, devotion to God, and observance of spiritual rituals. Hatha yoga is the path
which has physical health and balance as a primary
goal, for its practitioners believe that greater mental
and spiritual awareness can be brought about with a
healthy and pure body.
The origins of hatha yoga have been traced back
to the eleventh century A.D. The Sanskrit word
ha means ‘‘sun’’ and tha means ‘‘moon,’’ and thus
hatha, or literally sun-moon yoga, strives to balance
opposing parts of the physical body, the front and
back, left and right, top and bottom. Some yoga
masters (yogis) claim that hatha yoga was originally
developed by enlightened teachers to help people
survive during the Age of Kali, or the spiritual dark
ages, in which Hindus believe we are now living.
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Hatha yoga

protein diet, vitamin supplements of niacin, and by
avoiding the stresses that contribute to attacks of
symptoms.

Hatha yoga

The original philosophers of yoga developed it as
an eight-fold path to complete health. These eight steps
include moral and ethical considerations (such as
honesty, non-aggression, peacefulness, non-stealing,
generosity, and sexual propriety), self-discipline
(including purity, simplicity, devotion to God, and
self-knowledge), posture, breath control, control of
desires, concentration, meditation, and happiness.
According to yogis, if these steps are followed diligently, a person can reach high levels of health and
mental awareness.
As it has subsequently developed, hatha yoga
has concentrated mainly on two of the eight paths,
breathing and posture. Yogis believe breathing to be
the most important metabolic function; we breathe
roughly 23,000 times per day and use about 4,500
gallons of air, which increases during exercise. Thus,
breathing is extremely important to health, and
prana, or life-force, is found most abundantly in the
air and in the breath. If we are breathing incorrectly,
we are hampering our potential for optimal health.
Pranayama, literally the ‘‘science of breathing’’ or
‘‘control of life force,’’ is the yogic practice of breathing correctly and deeply.
In addition to breathing, hatha yoga utilizes
asanas, or physical postures, to bring about flexibility,
balance and strength in the body. Each of these
postures has a definite form and precise steps for
achieving the desired position and for exiting it.
These postures, yogis maintain, have been scientifically developed to increase circulation and health
in all parts of the body, from the muscular tissues
to the glands and internal organs. Yogis claim that
although hatha yoga can make the body as strong
and fit as any exercise program, its real benefits come
about because it is a system of maintenance and
balance for the whole body.
Yoga was brought to America in the late 1800s,
when Swami Vivekananda, an Indian yogi, presented
a lecture on yoga in Chicago. Hatha yoga captured
the imagination of the Western mind, because accomplished yogis could demonstrate incredible levels
of fitness, flexibility, and control over their bodies
and metabolism. Yoga has flourished in the West.
Americans have brought to yoga their energy and
zest for innovation, which troubles some Indian
yogis and encourages others, as new variations and
schools of yoga have developed. For instance, power
yoga is a recent Americanized version of yoga which
takes hatha yoga principles and speeds them up into
an extremely rigorous aerobic workout, and many
strict hatha yoga teachers oppose this sort of change
to their philosophy. Other variations of hatha yoga
1682

in America now include Iyengar, Ashtanga, Kripalu,
Integral, Viniyoga, Hidden Language, and Bikram
yoga, to name a few. Sivananda yoga was practiced
by Lilias Folen, who was responsible for introducing
many Americans to yoga through public television.
Iyengar yoga was developed by B.K.S. Iyengar,
who is widely accepted as one of the great living yogis.
Iyengar uses classical hatha yoga asanas and breathing
techniques, but emphasizes great precision and strict
form in the poses, and uses many variations on a few
postures. Iyengar allows the use of props such as belts,
ropes, chairs, and blocks to enable students to get into
postures they otherwise couldn’t. In this respect,
Iyengar yoga is good for physical therapy because it
assists in the manipulation of inflexible or injured
areas.
Ashtanga yoga, made popular by yogi K. Patabhi
Jois, also uses hatha yoga asanas, but places an
emphasis on the sequences in which these postures
are performed. Ashtanga routines often unfold like
long dances with many positions done quickly one
after the other. Ashtanga is thus a rigorous form of
hatha yoga, and sometimes can resemble a difficult
aerobic workout. Ashtanga teachers claim that this
form of yoga uses body heat, sweating, and deep
breathing to purify the body.
Kripalu yoga uses hatha yoga positions but
emphasizes the mental and emotional components
of each asana. Its teachers believe that tension and
long-held emotional problems can be released from
the body by a deep and meditative approach to the
yoga positions. Integral yoga seeks to combine all the
paths of yoga, and is generally more meditative than
physical, emphasizing spirituality and awareness in
everyday life. Viniyoga tries to adapt hatha yoga
techniques to each individual body and medical problem. Hidden Language yoga was developed by Swami
Sivananda Radha, a Western man influenced by
Jungian psychology. It emphasizes the symbolic and
psychological parts of yoga postures and techniques.
Its students are encouraged to write journals and participate in group discussions as part of their practice.
Bikram yoga has become very popular in the late
1990s, as its popular teacher, Bikram Choudury,
began teaching in Beverly Hills and has been endorsed
by many famous celebrities. Bikram yoga uses the
repetition of 26 specific poses and two breathing
techniques to stretch and tone the whole body.
A hatha yoga routine consists of a series of physical
postures and breathing techniques. Routines can take
anywhere from 20 minutes to two hours, depending on
the needs and ability of the practitioner. Yoga should
GALE ENCYCLOPEDIA OF MEDICINE

Yoga asanas consist of three basic movements:
backward bends, forward bends, and twisting movements. These postures are always balanced; a back
bend should be followed with a forward bend, and
a leftward movement should be followed by one to
the right. Diaphragm breathing is important during
the poses, where the breath begins at the bottom of the
lungs. The stomach should move outward with the inhalation and relax inward during exhalation. The breath
should be through the nose at all times during hatha
asanas. Typically, one inhales during backward bends
and exhales during forward bending movements.
The mental component in yoga is as important as
the physical movements. Yoga is not a competitive
sport, but a means to self-awareness and self-improvement. An attitude of attention, care, and non-criticism
is important; limitations should be acknowledged and
calmly improved. Patience is important, and yoga
stretches should be slow and worked up to gradually.
The body should be worked with, and never against,
and a person should never overexert. A yoga stretch
should be done only so far as proper form and alignment of the whole body can be maintained. Some
yoga stretches can be uncomfortable for beginners,
and part of yoga is learning to distinguish between
sensations that are beneficial and those that can signal
potential injury. A good rule is that positions should
be stopped when there is sharp pain in the joints,
muscles, or tendons.

Preparations
All that is needed to perform hatha yoga is a flat
floor and adequate space for stretching out. A wellventilated space is preferable, for facilitating proper
breathing technique. Yoga mats are available which
provide non-slip surfaces for standing poses. Loose,
comfortable clothing should be worn. Yoga should be
done on an empty stomach; a general rule is to wait
three hours after a meal.
Yoga is an exercise that can be done anywhere and
requires no special equipment. Yoga uses only gravity
and the body itself as resistance, so it is a low-impact
activity excellent for those who don’t do well with
other types of exercise. The mental component of
yoga can appeal to those who get bored easily with
GALE ENCYCLOPEDIA OF MEDICINE

Hatha yoga

always be adapted to one’s state of health; that is, a
shorter and easier routine should be used when a person
is fatigued. Yoga is ideally practiced at the same time
every day, to encourage the discipline of the practice. It
can be done at any time of day; some prefer it in the
morning as a wake-up routine, while others like to wind
down and de-stress with yoga at the end of the day.

KEY TERMS
Asana—Yoga posture or stance.
Diaphragm breathing—Method of deep breathing
using the entire lungs.
Dyana—Yoga meditation.
Meditation—Technique of mental relaxation.
Prana—Yoga term for life-enhancing nutrient
found in air, food and water.
Pranayama—Yoga method of breathing.

exercise. By the same token, yoga can be a good stress
management tool for those who prefer movement to
sitting meditation.

Precautions
As with any exercise program, people should
check with their doctors before starting yoga practice
for the first time. Those with medical conditions, injuries or spinal problems should find a yoga teacher
familiar with their conditions before beginning yoga.
Pregnant women, particularly after the third month of
pregnancy, should only perform a few yoga positions
with the supervision of an experienced teacher. Some
yoga asanas can be very difficult, and potentially
injurious, for beginners, so teachers should always be
consulted as preparation for advanced yoga positions.
Certain yoga positions should not be performed by
those with fevers, or during menstruation.

Side effects
Those just beginning hatha yoga programs often
report fatigue and soreness throughout the body, as
yoga stretches and exercises muscles and tendons
which are often long-neglected. Some yogic breathing
and meditation techniques can be difficult for beginners and can cause dizziness or disorientation; these
are best performed under the guidance of a teacher.
Resources
BOOKS

Feuerstein, Georg. Yoga for Dummies. New York: IDG
Books, 1999.
PERIODICALS

Yoga International Magazine. R.R. 1 Box 407, Honesdale,
PA 18431. <http://www.yimag.com>.
Yoga Journal. P.O. Box 469088, Escondido, CA 92046.
<http://www.yogajournal.com>.
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Head and neck cancer

ORGANIZATIONS

International Association of Yoga Therapists (IAYT). 4150
Tivoli Ave., Los Angeles, CA 90066.

Douglas Dupler, MA

Haverhill fever see Rat-bite fever
Hay fever see Allergic rhinitis
HBF test see Fetal hemoglobin test
HCG see Infertility drugs

Head and neck cancer
Definition
The term head and neck cancers refers to a group
of cancers found in the head and neck region. This
includes tumors found in:


The oral cavity (mouth). The lips, the tongue, the
teeth, the gums, the lining inside the lips and cheeks,
the floor of the mouth (under the tongue), the roof of
the mouth and the small area behind the wisdom
teeth are all included in the oral cavity.



The oropharynx (which includes the back one-third
of the tongue, the back of the throat and the tonsils).



Nasopharynx (which includes the area behind the
nose).



Hypopharynx (lower part of the throat).



The larynx (voice box, located in front of the neck,
in the region of the Adam’s apple). In the larynx, the
cancer can occur in any of the three regions: the
glottis (where the vocal cords are); the supraglottis
(the area above the glottis); and the subglottis (the
area that connects the glottis to the windpipe).

The most frequently occurring cancers of the head
and neck area are oral cancers and laryngeal cancers.
Almost half of all the head and neck cancers occur
in the oral cavity, and a third of the cancers are found
in the larynx. By definition, the term ‘‘head and neck
cancers’’ usually excludes tumors that occur in the
brain.

Description
Head and neck cancers involve the respiratory
tract and the digestive tract; and they interfere with
the functions of eating and breathing. Laryngeal cancers affect speech. Loss of any of these functions is
1684

significant. Hence, early detection and appropriate
treatment of head and neck cancers is of utmost
importance.
Roughly 10% of all cancers are related to the head
and the neck. It is estimated that more than 55,000
Americans will develop cancer of the head and neck in
1998, and nearly 13,000 will die from the disease. The
American Cancer Society estimates that in 1998,
approximately, 11,100 new cases of laryngeal cancer
alone will be diagnosed and 4,300 people will die of
this disease. Oral cancer is the sixth most common
cancer in the United States. Approximately 40,000
new cases are diagnosed each year and it causes at
least 8,000 deaths. Among the major cancers, the survival rate for head and neck cancers is one of the
poorest. Less than 50% of the patients survive five
years or more after initial diagnosis. This is because
the early signs of head and neck cancers are frequently
ignored. Hence, when it is first diagnosed, it is often
in an advanced stage and not very amenable to
treatment.
The risk for both oral cancer and laryngeal cancer
seems to increase with age. Most of the cases occur in
individuals over 40 years of age, the average age at
diagnosis being 60. While oral cancer strikes men twice
as often as it does women, laryngeal cancer is four
times more common in men than in women. Both
diseases are more common in black Americans than
among whites.

Causes and symptoms
Although the exact cause for these cancers is
unknown, tobacco is regarded as the single greatest
risk factor: 75–80% of the oral and laryngeal cancer
cases occur among smokers. Heavy alcohol use has
also been included as a risk factor. A combination of
tobacco and alcohol use increases the risk for oral
cancer by 6–15 times more than for users of either
substance alone. In rare cases, irritation to the lining
of the mouth, due to jagged teeth or ill-fitting dentures, has been known to cause oral cancer. Exposure
to asbestos appears to increase the risk of developing
laryngeal cancer.
In the case of lip cancer, just like skin cancer,
exposure to sun over a prolonged period has been
shown to increase the risk. In the Southeast Asian
countries (India and Sri Lanka), chewing of betel nut
has been associated with cancer of the lining of the
cheek. An increased incidence of nasal cavity cancer
has been observed among furniture workers, probably
due to the inhalation of wood dust. A virus (EpsteinBarr) has been shown to cause nasopharyngeal cancer.
GALE ENCYCLOPEDIA OF MEDICINE



Mouth and oral cavity: a sore that does not heal
within two weeks, unusual bleeding from the teeth
or gums, a white or red patch in the mouth, a lump or
thickening in the mouth, throat, or tongue.



Larynx: persistent hoarseness or sore throat, difficulty breathing, or pain.



Hypopharynx and oropharynx: difficulty in swallowing or chewing food, ear pain.



Nose, sinuses, and nasopharyngeal cavity: pain,
bloody discharges from the nose, blocked nose, and
frequent sinus infections that do not respond to
standard antibiotics.

When detected early and treated appropriately,
head and neck cancers have an excellent chance of
being cured completely.

Diagnosis
Specific diagnostic tests used depend on the location of the cancer. The standard tests are:
Physical examination
The first step in diagnosis is a complete and
thorough examination of the oral and nasal cavity,
using mirrors and other visual aids. The tongue and
the back of the throat are examined as well. Any
suspicious looking lumps or lesions are examined
with fingers (palpation). In order to look inside the
larynx, the doctor may sometimes perform a procedure known as laryngoscopy. In indirect laryngoscopy, the doctor looks down the throat with a
small, long handled mirror. Sometimes the doctor
inserts a lighted tube (laryngoscope or a fiberoptic
scope) through the patient’s nose or mouth. As the
tube goes down the throat, the doctor can observe
areas that cannot be seen by a simple mirror. This
procedure is called a direct laryngoscopy. Sometimes patients may be given a mild sedative to help
them relax, and a local anesthetic to ease any
discomfort.
Blood tests
The doctor may order blood or other immunological tests. These tests are aimed at detecting antibodies to the Epstein-Barr virus, which has been
known to cause cancer of the nasopharynx.
GALE ENCYCLOPEDIA OF MEDICINE

Imaging tests
X rays of the mouth, the sinuses, the skull, and
the chest region may be required. A computed tomography scan (CT scan), a procedure in which a computer takes a series of x-ray pictures of areas inside
the body, may be done. Ultrasonograms (images
generated using sound waves) or an MRI (magnetic
resonance imaging, a procedure in which a picture is
created using magnets linked to a computer), are alternate procedures which a doctor may have done to
get detailed pictures of the areas inside the body.
Biopsy
When a sore does not heal or a suspicious patch or
lump is seen in the mouth, larynx, nasopharynx, or
throat, a biopsy may be performed to rule out the
possibility of cancer. The biopsy is the most definitive
diagnostic tool for detecting the cancer. If cancerous
cells are detected in the biopsied sample, the doctor
may perform more extensive tests in order to find
whether, and to where, the cancer may have spread.

Treatment
The cancers can be treated successfully if diagnosed early. The choice of treatment depends on the
size of the tumor, its location, and whether it has
spread to other parts of the body.
In the case of lip and mouth cancers, sometimes
surgery is performed to remove the cancer. Radiation
therapy, which destroys the cancerous cells, is also one
of the primary modes of treatment, and may be used
alone or in combination with surgery. If lip surgery
is drastic, rehabilitation cosmetic or reconstructive
surgery may have to be considered.
Cancers of the nasal cavity are often diagnosed
late because they have no specific symptoms in their
early stages, or the symptoms may just resemble
chronic sinusitis. Hence, treatment is often complex,
involving a combination of radiotherapy and surgery.
Surgery is generally recommended for small tumors.
If the cancer cannot be removed by surgery, radiotherapy is used alone.
Treatment of oropharynx cancers (cancers that
are either in the back of the tongue, the throat, or the
tonsils) generally involves radiation therapy and/or
surgery. After aggressive surgery and radiation, rehabilitation is often necessary and is an essential part of
the treatment. The patient may experience difficulties
with swallowing, chewing, and speech and may require
a team of health care workers, including speech therapists, prosthodontists, occupational therapists, etc.
1685

Head and neck cancer

Head and neck cancers are one of the easiest to
detect. The early signs can be both seen and felt. The
signs and symptoms depend on the location of the
cancer:

Head and neck cancer

used. In order to treat advanced cancers, a combination of surgery and radiation therapy is often used.
Because the chances of a cure in the case of advanced
laryngeal cancers are rather low with current therapies, the patient may be advised to participate in clinical trials so they may get access to new experimental
drugs and procedures, such as chemotherapy, that are
being evaluated.
When only part of the larynx is removed, a relatively slight change in the voice may occur—the
patient may sound slightly hoarse. However, in a
total laryngectomy, the entire voice box is removed.
The patients then have to re-learn to speak using
different approaches, such as esophageal speech,
tracheo-esophageal (TE) speech, or by means of an
artificial larynx.
In esophageal speech, the patients are taught how
to create a new type of voice by forcing air through the
esophagus (food pipe) into the mouth. This method
has a high success rate of approximately 65% and
patients are even able to go back to jobs that require
a high level of verbal communication, such as telephone operators and salespersons.

A specimen of a squamous cell carcinoma of the tongue and
jaw. (Custom Medical Stock Photo. Reproduced by permission.)

Cancers of the nasopharynx are different from
the other head and neck cancers in that there does
not appear to be any association between alcohol and
tobacco use and the development of the cancer. In
addition, the incidence is seen primarily in two
age groups: young adults and 50–70 year-olds. The
Epstein-Barr virus has been implicated as the causative
agent in most patients. While 80–90% of small tumors
are curable by radiation therapy, advanced tumors that
have spread to the bone and cranial nerves are difficult
to control. Surgery is not very helpful and, hence, is
rarely attempted. Radiation remains the only treatment
of choice to treat the cancer that has metastasized
(traveled) to the lymph nodes in the neck.
In the case of cancer of the larynx, radiotherapy is
the first choice to treat small lesions. This is done in an
attempt to preserve the voice. If the cancer recurs later,
surgery may be attempted. If the cancer is limited to
one of the two vocal cords, laser excision surgery is
1686

In the second approach, TE speech, a small opening, called a fistula, is created surgically between the
trachea (breathing tube to the lungs) and the esophagus (tube into the stomach) to carry air into the throat.
A small tube, known as the ‘‘voice prosthesis,’’ is
placed in the opening of the fistula to keep it open
and to prevent food and liquid from going down into
the trachea. In order to talk, the stoma (or the opening
made at the base of the neck) must be covered with
one’s thumb during exhalation. As the air is forced out
from the trachea into the esophagus, it vibrates the
walls of the esophagus. This produces a sound that
is then modified by the lips and tongue to produce
normal sounding speech.
In the third approach, an artificial larynx, a battery driven vibrator, is placed on the outside of the
throat. Sound is created as air passes through
the stoma (opening made at the base of the neck) and
the mouth forms words.

Prognosis
Oral Cavity
With early detection and immediate treatment,
survival rates can be dramatically improved. For lip
and oral cancer, if detected at its early stages, almost
80% of the patients survive five years or more.
However, when diagnosed at the advanced stages,
the five year survival rate drops to a mere 18%.
GALE ENCYCLOPEDIA OF MEDICINE

Cancers of the nasal cavity often go undetected
until they reach an advanced stage. If diagnosed at the
early stages, the five-year survival rates are 60–70%.
However, if cancers are more advanced, only 10–30%
of the patients survive five years or more.
Oropharynx
In cancer of the oropharynx, 60–80% of the
patients survive five years or more if the cancer is
detected in the early stages. As the cancer advances,
the survival rate drops to 15–30%.
Nasopharynx
Patients who are diagnosed with early stage cancers that have originated in the nasopharynx have an
excellent chance of a complete cure (almost 95%).
Unfortunately, most of the time, the patients are in
an advanced stage at the time of initial diagnosis. With
the new chemotherapy drugs, the five year survival rate
has improved and 5–40% of the patients survive five
years or longer.
Larynx
Small cancers of the larynx have an excellent fiveyear survival rate of 75–95%. However, as with most
of the head and neck cancers, the survival rates drop
dramatically as the cancer advances. Only 15–25% of
the patients survive five years or more after being
initially diagnosed with advanced laryngeal cancer.

Prevention
Refraining from the use of all tobacco products
(cigarettes, cigars, pipe tobacco, chewing tobacco),
consuming alcohol in moderation, and practicing
good oral hygiene are some of the measures that one
can take to prevent head and neck cancers. Since there
is an association between excessive exposure to the sun
and lip cancer, people who spend a lot of time outdoors in the sun should protect themselves from the
sun’s harmful rays. Regular physical examinations, or
mouth examination by the patient himself, or by the
patient’s doctor or dentist, can help detect oral cancer
in its very early stages.
Since working with asbestos has been shown to
increase one’s risk of getting cancer of the larynx,
asbestos workers should follow safety rules to avoid
inhaling asbestos fibers. Also, malnutrition and vitamin deficiencies have been shown to have some association with an increased incidence of head and neck
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Chemotherapy—Treatment of cancer with synthetic drugs that destroy the tumor either by inhibiting the growth of the cancerous cells or by killing
the cancer cells.
Clinical trials—Highly regulated and carefully
controlled patient studies, where either new drugs
to treat cancer or novel methods of treatment are
investigated.
Computerized tomography scan (CT scan)—A
medical procedure where a series of X-rays are
taken and put together by a computer in order to
form detailed pictures of areas inside the body.
Laryngoscopy—A medical procedure that uses
flexible, lighted, narrow tubes inserted through
the mouth or nose to examine the larynx and
other areas deep inside the neck.
Magnetic resonance imaging (MRI)—A medical
procedure used for diagnostic purposes where
pictures of areas inside the body can be created
using a magnet linked to a computer.
Radiation therapy—Treatment using high energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Stoma—When the entire larynx must be surgically
removed, an opening is surgically created in the
neck so that the windpipe can be brought out to the
neck. This opening is called the stoma.
Ultrasonogram—A procedure where high-frequency sound waves that cannot be heard by
human ears are bounced off internal organs and
tissues. These sound waves produce a pattern of
echoes which are then used by the computer to
create sonograms, or pictures of areas inside the
body.
X rays—High energy radiation used in high doses,
either to diagnose or treat disease.

cancers. The American Cancer Society, therefore,
recommends eating a healthy diet, consisting of at
least five servings of fruits and vegetables every day,
and six servings of food from other plant sources such
as cereals, breads, grain products, rice, pasta and
beans. Reducing one’s intake of high-fat food from
animal sources is advised.
1687

Head and neck cancer

Nose and sinuses

Head injury

Resources

are due to head injuries, as are most of the disabilities
that occur after trauma.

ORGANIZATIONS

American Association of Oral and Maxillofacial Surgeons.
9700 West Bryn Mawr Ave., Rosemont, IL 60018-5701.
(847) 678-6200. <http://www.aaoms.org>.
International Association of Laryngectomees (IAL). 7440
North Shadeland Ave., Suite 100, Indianapolis, IN
46250. <http://www.larynxlink.com/>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
National Oral Health Information ClearingHouse; 1 NOHIC
Way, Bethesda, MD 20892-3500. (301)-402-7364.
Oral Health Education Foundation, Inc. 5865 Colonist Drive,
P.O. Box 396, Fairburn, GA 30213. (770) 969-7400.

Lata Cherath, PhD

Head injury
Definition
Injury to the head may damage the scalp, skull or
brain. The most important consequence of head
trauma is traumatic brain injury. Head injury may
occur either as a closed head injury, such as the head
hitting a car’s windshield, or as a penetrating head
injury, as when a bullet pierces the skull. Both may
cause damage that ranges from mild to profound.
Very severe injury can be fatal because of profound
brain damage.

Description
External trauma to the head is capable of damaging the brain, even if there is no external evidence of
damage. More serious injuries can cause skull fracture, blood clots between the skull and the brain, or
bruising and tearing of the brain tissue itself.
Injuries to the head can be caused by traffic accidents, sports injuries, falls, workplace accidents,
assaults, or bullets. Most people have had some type
of head injury at least once in their lives, but rarely do
they require a hospital visit.
However, each year about two million people suffer from a more serious head injury, and up to 750,000
of them are severe enough to require hospitalization.
Brain injury is most likely to occur in males between
ages 15 and 24, usually as a result of car and motorcycle accidents. About 70% of all accidental deaths
1688

A person who has had a head injury and who is
experiencing the following symptoms should seek
medical care immediately:


serious bleeding from the head or face



loss of consciousness, however brief



confusion and lethargy



lack of pulse or breathing



clear fluid drainage from the nose or ear

Causes and symptoms
A head injury may cause damage both from the
direct physical injury to the brain and from secondary
factors, such as lack of oxygen, brain swelling, and
disturbance of blood flow. Both closed and penetrating head injuries can cause swirling movements
throughout the brain, tearing nerve fibers and causing
widespread bleeding or a blood clot in or around the
brain. Swelling may raise pressure within the skull
(intracranial pressure) and may block the flow of
oxygen to the brain.
Head trauma may cause a concussion, in which
there is a brief loss of consciousness without visible
structural damage to the brain. In addition to loss of
consciousness, initial symptoms of brain injury may
include:


memory loss and confusion



vomiting



dizziness



partial paralysis or numbness



shock



anxiety

After a head injury, there may be a period of
impaired consciousness followed by a period of confusion and impaired memory with disorientation and a
breakdown in the ability to store and retrieve new
information. Others experience temporary amnesia
following head injury that begins with memory loss
over a period of weeks, months, or years before the
injury (retrograde amnesia). As the patient recovers,
memory slowly returns. Post-traumatic amnesia refers
to loss of memory for events during and after the
accident.
Epilepsy occurs in 2–5% of those who have had a
head injury; it is much more common in people who
have had severe or penetrating injuries. Most cases of
epilepsy appear right after the accident or within the
GALE ENCYCLOPEDIA OF MEDICINE

Closed head injury
Closed head injury refers to brain injury without
any penetrating injury to the brain. It may be the result
of a direct blow to the head; of the moving head being
rapidly stopped, such as when a person’s head hits a
windshield in a car accident; or by the sudden deceleration of the head without its striking another object.
The kind of injury the brain receives in a closed head
injury is determined by whether or not the head was
unrestrained upon impact and the direction, force, and
velocity of the blow. If the head is resting on impact,
the maximum damage will be found at the impact site.
A moving head will cause a ‘‘contrecoup injury’’ where
the brain damage occurs on the side opposite the point
of impact, as a result of the brain slamming into that
side of the skull. A closed head injury also may occur
without the head being struck, such as when a person
experiences whiplash. This type of injury occurs
because the brain is of a different density than the
skull, and can be injured when delicate brain tissues
hit against the rough, jagged inner surface of the skull.
Penetrating head injury
If the skull is fractured, bone fragments may be
driven into the brain. Any object that penetrates the
skull may implant foreign material and dirt into the
brain, leading to an infection.
Skull fracture
A skull fracture is a medical emergency that must
be treated promptly to prevent possible brain damage.
Such an injury may be obvious if blood or bone fragments are visible, but it’s possible for a fracture to have
occurred without any apparent damage. A skull fracture should be suspected if there is:


blood or clear fluid leaking from the nose or ears



unequal pupil size



bruises or discoloration around the eyes or behind
the ears



swelling or depression of part of the head

can press against brain tissue, causing symptoms from
a few hours to a few weeks after the injury. If the
clot is located between the bones of the skull and the
covering of the brain (dura), it is called an epidural
hematoma. If the clot is between the dura and the
brain tissue itself, the condition is called a subdural
hematoma. In other cases, bleeding may occur deeper
inside the brain. This condition is called intracerebral
hemorrhage or intracerebral contusion (from the word
for bruising).
In any case, if the blood flow is not stopped, it can
lead to unconsciousness and death. The symptoms of
bleeding within the skull include:


nausea and vomiting



headache



loss of consciousness



unequal pupil size



lethargy
Postconcussion syndrome

If the head injury is mild, there may be no symptoms other than a slight headache. There also may be
confusion, dizziness, and blurred vision. While the
head injury may seem to have been quite mild, in
many cases symptoms persist for days or weeks. Up
to 60% of patients who sustain a mild brain injury
continue to experience a range of symptoms called
‘‘postconcussion syndrome,’’ as long as six months
or a year after the injury.
The symptoms of postconcussion syndrome can
result in a puzzling interplay of behavioral, cognitive,
and emotional complaints that can be difficult to diagnose, including:


headache



dizziness



mental confusion



behavior changes



memory loss



cognitive deficits



depression



emotional outbursts

Intracranial hemorrhage
Bleeding (hemorrhage) inside the skull may
accompany a head injury and cause additional
damage to the brain. A blood clot (hematoma) may
occur if a blood vessel between the skull and the brain
ruptures; when the blood leaks out and forms a clot, it
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
The extent of damage in a severe head injury can
be assessed with computed tomography (CT) scan,
magnetic resonance imaging (MRI), positron emission
tomography (PET) scans, electroencephalograms
1689

Head injury

first year, and become less likely with increased time
following the accident.

Head injury

experts warn that there is a good chance that patient
complaints after a mild head injury will be downplayed or dismissed. In the case of mild head injury
or postconcussion syndrome, CT and MRI scans,
electroencephalograms (EEG), and routine neurological evaluations all may be normal because the damage
is so subtle. In many cases, these tests can’t detect the
microscopic damage that occurs when fibers are
stretched in a mild, diffuse injury. In this type of
injury, the axons lose some of their covering and
become less efficient. This mild injury to the white
matter reduces the quality of communication between
different parts or the brain. A PET scan, which evaluates cerebral blood flow and brain metabolism, may
be of help in diagnosing mild head injury.
Patients with continuing symptoms after a mild
head injury should call a local chapter of a head-injury
foundation that can refer patients to the best nearby
expert.

Treatment
If a concussion, bleeding inside the skull, or skull
fracture is suspected, the patient should be kept quiet
in a darkened room, with head and shoulders raised
slightly on pillow or blanket.

A three-dimensional computed tomography (CT) scan of
a human skull showing a depressed skull fracture above
the right eye. (Custom Medical Stock Photo. Reproduced by
permission.)

(EEG), and routine neurological and neuropsychological evaluations.
Doctors use the Glasgow Coma Scale to evaluate
the extent of brain damage based on observing a
patient’s ability to open his or her eyes, respond verbally, and respond to stimulation by moving (motor
response). Patients can score from three to 15 points
on this scale. People who score below eight when they
are admitted usually have suffered a severe brain
injury and will need rehabilitative therapy as they
recover. In general, higher scores on the Glasgow
Coma Scale indicate less severe brain injury and a
better prognosis for recovery.
Patients with a mild head injury who experience
symptoms are advised to seek out the care of a specialist; unless a family physician is thoroughly familiar
with medical literature in this newly emerging area,
1690

After initial emergency treatment, a team of specialists may be needed to evaluate and treat the problems that result. A penetrating wound may require
surgery. Those with severe injuries or with a deteriorating level of consciousness may be kept hospitalized
for observation. If there is bleeding inside the skull, the
blood may need to be surgically drained; if a clot has
formed, it may need to be removed. Severe skull fractures also require surgery. Supportive care and specific
treatments may be required if the patient experiences
further complications. People who experience seizures, for example, may be given anticonvulsant
drugs, and people who develop fluid on the brain
(hydrocephalus) may have a shunt inserted to drain
the fluid.
In the event of long-term disability as a result of
head injury, there are a variety of treatment programs
available, including long-term rehabilitation, coma
treatment centers, transitional living programs, behavior management programs, life-long residential or
day treatment programs and independent living
programs.

Prognosis
Prompt, proper diagnosis and treatment can help
alleviate some of the problems after a head injury.
GALE ENCYCLOPEDIA OF MEDICINE

Computed tomography scan (CT)—A diagnostic
technique in which the combined use of a computer and x rays produce clear cross-sectional images
of tissue. It provides clearer, more detailed information than x rays alone.
Electroencephalogram (EEG)—A record of the tiny
electrical impulses produced by the brain’s activity. By measuring characteristic wave patterns, the
EEG can help diagnose certain conditions of the
brain.
Magnetic resonance imaging (MRI)—A diagnostic
technique that provides high quality cross-sectional
images of organs within the body without x rays or
other radiation.
Positron emission tomography (PET) scan—A
computerized diagnostic technique that uses radioactive substances to examine structures of the
body. When used to assess the brain, it produces
a three-dimensional image that reflects the metabolic and chemical activity of the brain.

mild brain injury during childhood could speed up
expression of schizophrenia in those who were
already likely to get the disorder because of genetics.
Those with a history of a childhood brain injury,
even a minor one, were more likely to get familial
schizophrenia than a sibling and to have earlier
onset. Another study in 2003 found that people
who had a history of a severe head injury were four
times more likely to develop Parkinson’s disease
than the average population. Those requiring hospitalization for their head injuries were 11 times as
likely. The risk did not increase for people receiving
mild head injuries.

Prevention
Many severe head injuries could be prevented by
wearing protective helmets during certain sports, or
when riding a bike or motorcycle. Seat belts and airbags can prevent many head injuries that result from
car accidents. Appropriate protective headgear always
should be worn on the job where head injuries are a
possibility.
Resources
PERIODICALS

However, it usually is difficult to predict the outcome
of a brain injury in the first few hours or days; a
patient’s prognosis may not be known for many
months or even years.
The outlook for someone with a minor head injury
generally is good, although recovery may be delayed
and symptoms such as headache, dizziness, and cognitive problems can persist for up to a year or longer
after an accident. This can limit a person’s ability to
work and cause strain in personal relationships.
Serious head injuries can be devastating, producing permanent mental and physical disability.
Epileptic seizures may occur after a severe head injury,
especially a penetrating brain injury, a severe skull
fracture, or a serious brain hemorrhage. Recovery
from a severe head injury can be very slow, and it
may take five years or longer to heal completely. Risk
factors associated with an increased likelihood of memory problems or seizures after head injury include age,
length and depth of coma, duration of post-traumatic
and retrograde amnesia, presence of focal brain
injuries, and initial Glasgow Coma Scale score.
As researchers learn more about the long-term
effects of head injuries, they have begun to uncover
links to later conditions. A 2003 report found that
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Childhood Head Injury Tied to Later Schizophreia.’’ The
Brown University Child and Adolescent Behavior Letter
June 2003: 5.
‘‘Link to Head Injury Found.’’ Pain & Central Nervous
System Week June 9, 2003: 3.
ORGANIZATIONS

American Epilepsy Society. 342 North Main Street, West
Hartford, CT 06117-2507. (860) 586-7505. <http://
www.aesnet.org>.
Brain Injury Association. 1776 Massachusetts Ave. NW,
Ste. 100, Washington, DC 20036. (800) 444-6443.
Family Caregiver Alliance. 425 Bush St., Ste. 500, San
Francisco, CA 94108. (800) 445-8106. <http://
www.caregiver.org>.
Head Injury Hotline. PO Box 84151, Seattle WA 98124.
(206) 621- 8558. <http://www.headinjury.com>.
Head Trauma Support Project, Inc. 2500 Marconi Ave., Ste.
203, Sacramento, CA 95821. (916) 482-5770.
National Head Injury Foundation. 333 Turnpike Rd.,
Southboro, MA 01722. (617) 485-9950.

Carol A. Turkington
Teresa G. Odle

Head lice see Lice infestation
Head trauma see Head injury
1691

Head injury

KEY TERMS

Headache

Headache
Definition
A headache involves pain in the head which can
arise from many disorders or may be a disorder in and
of itself.

Description
There are three types of primary headaches:
tension-type (muscular contraction headache),
migraine (vascular headaches), and cluster. Virtually
everyone experiences a tension-type headache at some
point. An estimated 18% of American women suffer
migraines, compared to 6% of men. Cluster headaches
affect fewer than 0.5% of the population, and men
account for approximately 80% of all cases.
Headaches caused by illness are secondary headaches
and are not included in these numbers.
Approximately 40–45 million people in the United
States suffer chronic headaches. Headaches have an
enormous impact on society due to missed workdays
and productivity losses.

Causes and symptoms
Traditional theories about headaches link tensiontype headaches to muscle contraction, and migraine
and cluster headaches to blood vessel dilation (swelling). Pain-sensitive structures in the head include
blood vessel walls, membranous coverings of the
brain, and scalp and neck muscles. Brain tissue itself
has no sensitivity to pain. Therefore, headaches may
result from contraction of the muscles of the scalp,
face or neck; dilation of the blood vessels in the head;
or brain swelling that stretches the brain’s coverings.
Involvement of specific nerves of the face and head
may also cause characteristic headaches. Sinus inflammation is a common cause of headache. Keeping a
headache diary may help link headaches to stressful
occurrences, menstrual phases, food triggers, or
medication.
Tension-type headaches are often brought on by
stress, overexertion, loud noise, and other external
factors. The typical tension-type headache is described
as a tightening around the head and neck, and an
accompanying dull ache.
Migraines are intense throbbing headaches occurring on one or both sides of the head, usually on one
side. The pain is accompanied by other symptoms
such as nausea, vomiting, blurred vision, and aversion
to light, sound, and movement. Migraines often are
1692

triggered by food items, such as red wine, chocolate,
and aged cheeses. For women, a hormonal connection
is likely, since headaches occur at specific points in the
menstrual cycle, with use of oral contraceptives, or the
use of hormone replacement therapy after menopause.
Research shows that a complex interaction of nerves
and neurotransmitters in the brain act to cause
migraine headaches.
Cluster headaches cause excruciating pain. The
severe, stabbing pain centers around one eye, and eye
tearing and nasal congestion occur on the same side.
The headache lasts from 15 minutes to four hours and
may recur several times in a day. Heavy smokers are
more likely to suffer cluster headaches, which also are
associated with alcohol consumption.

Diagnosis
Since headaches arise from many causes, a physical exam assesses general health and a neurologic exam
evaluates the possibility of neurologic disease as a
cause for the headache. If the headache is the primary
illness, the doctor asks for a thorough history of the
headache. Questions revolve around its frequency and
duration, when it occurs, pain intensity and location,
possible triggers, and any prior symptoms. This information aids in classifying the headache.
Warning signs that should point out the need for
prompt medical intervention include:


‘‘Worst headache of my life.’’ This may indicate
subarachnoid hemorrhage from a ruptured aneurysm (swollen blood vessel) in the head or other
neurological emergency.



Headache accompanied by one-sided weakness,
numbness, visual loss, speech difficulty, or other
signs. This may indicate a stroke. Migraines may
include neurological symptoms.



Headache that becomes worse over a period of 6
months, especially if most prominent in the morning
or if accompanied by neurological symptoms. This
may indicate a brain tumor.



Sudden onset of headache. If accompanied by fever
and stiff neck, this can indicate meningitis.

Headache diagnosis may include neurological
imaging tests such as computed tomography scan
(CT scan) or magnetic resonance imaging (MRI).

Treatment
Headache treatment is divided into two forms:
abortive and prophylactic. Abortive treatment
GALE ENCYCLOPEDIA OF MEDICINE

Tension-type headaches can be treated with aspirin,
acetaminophen, ibuprofen, or naproxen. In early 1998,
the FDA approved extra-strength Excedrin, which
includes caffeine, for mild migraines. Physicians continue to investigate and monitor the best treatment
for migraines and generally prefer a stepped approach,
depending on headache severity, frequency and
impact on the patient’s quality of life. A group of
drugs called triptans are usually preferred for abortive treatment. About seven triptans are available
in the United States and the pill forms are considered
most effective. They should be taken as early as
possible during the typical migraine attack. The
most common prophylactic therapies include antidepressants, beta blockers, calcium channel blockers
and antiseizure medications. Antiseizure medications
have proven particularly effective at blocking the
actions of neurotransmitters that start migraine
attacks. Topiramate (Topamax) was shown effective
in several combined clinical trials in 2004 at 50 to 200
mg per day.
In 2004, a new, large study added evidence to
show the effectiveness of botulinum toxin type A
(Botox) treatment to prevent headache pain for those
with frequent, untreatable tension and migraine headaches. Patients were treated every three months, with
two to five injections each time. They typically
received relief within two to three weeks.
Cluster headaches may also be treated with ergotamine and sumatriptan, as well as by inhaling pure
oxygen. Prophylactic treatments include prednisone,
calcium channel blockers, and methysergide.

Alternative treatment
Alternative headache treatments include:


acupuncture or acupressure



biofeedback



chiropractic



herbal remedies using feverfew (Chrysanthemum
parthenium), valerian (Valeriana officinalis), white
willow (Salix alba), or skullcap (Scutellaria lateriflora), among others



homeopathic remedies chosen specifically for the
individual and his/her type of headache



hydrotherapy



massage



magnesium supplements

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Abortive—Referring to treatment that relieves
symptoms of a disorder.
Analgesics—A class of pain-relieving medicines,
including aspirin and Tylenol.
Biofeedback—A technique in which a person is
taught to consciously control the body’s response
to a stimulus.
Chronic—Referring to a condition that occurs frequently or continuously or on a regular basis.
Prophylactic—Referring to treatment that prevents
symptoms of a disorder from appearing.
Transcutaneous electrical nerve stimulation—A
method that electrically stimulates nerve and blocks
the transmission of pain signals, called TENS.



regular physical exercise



relaxation techniques, such as meditation and yoga



transcutaneous electrical nerve stimulation (TENS)
(A procedure that electrically stimulates nerves and
blocks the signals of pain transmission.)

Prognosis
Headaches are typically resolved through the use
of analgesics and other treatments. Research in 2004
showed that people who have migraine headaches
more often than once a month may be at increased
risk for stroke.

Prevention
Some headaches may be prevented by avoiding
triggering substances and situations, or by employing
alternative therapies, such as yoga and regular exercise. Since food allergies often are linked with headaches, especially cluster headaches, identification and
elimination of the allergy-causing food(s) from the diet
can be an important preventive measure.
Resources
PERIODICALS

Kruit, Mark C., et al. ‘‘Migraine as a Risk Factor for
Subclinical Brain Lesions.’’ JAMA, Journal of the
American Medical Association January 28, 2004:
427–435.
Norton, Patrice G. W. ‘‘Botox Stops Headache Pain in
Recalcitrant Cases.’’ Clinical Psychiatry News March
2004: 72.
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Headache

addresses a headache in progress, and prophylactic
treatment prevents headache occurrence.

Hearing aids

Taylor, Frederick, et al. ‘‘Diagnosis and Management of
Migraine in Family Practice.’’ Journal of Family
Practice January 2004: S3–S25.
ORGANIZATIONS

American Council for Headache Education (ACHE). 19
Mantua Road, Mt. Royal, NJ 08061. (800) 255-2243.
<http://www.achenet.org>.
National Headache Foundation. 428 W. St. James Place,
Chicago, IL 60614. (800) 843-2256. <http://
www.headaches.org>.

Julia Barrett
Teresa G. Odle

Hearing aids
Definition
A hearing aid is a device that can amplify sound
waves in order to help a deaf or hard-of-hearing
person hear sounds more clearly.

Purpose
Recent technology can help most people with
hearing loss understand speech better and achieve
better communication.

Precautions
It’s important that a person being fitted for a
hearing aid understand what an aid can and can’t do.
An aid can help a person hear better, but it won’t
return hearing to normal levels. Hearing aids boost
all sounds, not just those the person wishes to hear.
Especially when the source of sound is far away (such
as up on a stage), environmental noise can interfere
with good speech perception. And while the aid amplifies sound, it doesn’t necessarily improve the clarity
of the sound. A hearing aid is a machine, and can
never duplicate the true sound that people with normal hearing experience, but it will help the person take
advantage of the hearing that remains.

Description
More than 1,000 different models are available in
the United States. All of them include a microphone
(to pick up sound), amplifier (to boost sound
strength), a receiver or speaker (to deliver sound to
the ear), and are powered by a battery. Depending
1694

on the style, it’s possible to add features to filter or
block out background noise, minimize feedback,
lower sound in noisy settings, or boost power when
needed.
Hearing aids are either ‘‘monaural’’ (a hearing aid
for one ear), or ‘‘binaural’’ (for two ears); more than
65% of all users have binaural aids. Hearing aids are
divided into several different types:


digital



in-the-ear



in-the-canal



behind-the-ear



on-the-body

Digital aids are sophisticated, very expensive aids
that borrow computer technology to allow a person to
tailor an aid to a specific hearing loss pattern. Using
miniature computer chips, the aids can selectively
boost certain frequencies while leaving others alone.
This means a person could wear such an aid to a loud
party, and screen out unwanted background noise,
while tuning in on one-on-one conversations. The aid
is programmed by the dealer to conform to the
patient’s specific hearing loss. Some models can be
programmed to allow the wearer to choose different
settings depending on the noise of the environment.
In-the-ear aids are lightweight devices whose custom-made housings contain all the components; this
device fits into the ear canal with no visible wires or
tubes. It’s possible to control tone but not volume with
these aids, so they are helpful only for people with
mild hearing loss. Some people find these aids are
easier to put on and take off than behind-the-ear
aids. However, because they are custom-fit to a person’s ear, it is not possible to try on before ordering.
Some people find them uncomfortable in hot weather.
In-the-canal aids fit far into the ear canal, with
only a small bit extending into the external ear. The
smallest is the MicroCanal, which fits out of sight
down next to the eardrum and is removed with a
small transparent wire. These are extremely expensive,
but they are not visible, offer better acoustics, and are
easier to maintain. They can more closely mimic natural sound because of the position of the microphone;
this position also cuts down on wind noise. But their
small size makes them harder to handle, and their
battery is especially small and difficult to insert.
Adjusting the volume may be hard, since a person
must stick a finger down into the ear to adjust volume,
and this very tiny aid doesn’t have the power of other,
larger, aids.
GALE ENCYCLOPEDIA OF MEDICINE

Hearing aids

Ear mold
Connecting tube
Ear hook

On/off switch and
volume control
Sound tube

On/off switch

Microphone

Battery
compartment

Volume control
Battery compartment
BEHIND-THE-EAR HEARING AID

Microphone

IN-THE-EAR HEARING AID

Hearing aids are devices that can amplify sound waves to help a deaf or hard-of-hearing person hear sounds more clearly.
(Illustration by Electronic Illustrators Group.)

Behind-the-ear aids include a microphone, amplifier and receiver inside a small curved case worn
behind the ear; the case is connected to the earmold
by a short plastic tube. The earmold extends into the
ear canal. Some models have both tone and volume
control, plus a telephone pickup device. However,
many users think them unattractive and out of date;
and people who wear glasses find that the glasses
interfere with the aid’s fit. Others don’t have space
behind the ear for the mold to fit comfortably.
However, they do offer a few advantages.
Behind-the-ear aids:


don’t require as much maintenance



are easily interchangeable if they need to be serviced



are more powerful



are easier to handle than smaller aids



can provide better sound quality



tend to be more reliable

Eyeglass models are the same as behind-the-ear
devices, except that the case fits into an eyeglass frame
instead of resting behind the ears. Not many people
buy this type of aid, but those who do believe it’s less
obvious, although there is a tube that travels from the
temple of the glasses to the earmold. But it can be hard
to fit this type of aid, and repairs can be problematic.
GALE ENCYCLOPEDIA OF MEDICINE

Also, if the aid breaks, the person also loses the benefit
of the glasses.
CROS or the crossover system type of hearing aid
is often used in conjunction with the eyeglass model.
The CROS (contralateral routing of signal) system
features a microphone behind the ear that feeds the
amplified signal to the better ear, eliminating ‘‘head
shadow,’’ which occurs when the head blocks sound
from the better ear. This type may help make speech
easier to understand for people with a high-frequency
loss in both ears.
A BI-CROS system uses two microphones (one
above each ear) that send signals to a single amplifier.
Sound then travels to a single receiver, which transfers
it to the better ear via a conventional earmold.
On-the-body aids feature a larger microphone,
amplifier, and power supply inside a case carried
inside the pocket, or attached to clothing. The receiver
attaches directly to the earmold; its power comes
through a flexible wire from the amplifier. Although
larger than other aids, the on-the-body aids are more
powerful and easier to adjust than other devices. While
not popular for everyone, they are often used by
those with a profound hearing loss, or by very young
children. Some people who are almost totally deaf find
they need the extra power boost available only from a
body aid.
1695

Hearing aids

The latest aids on the market may eliminate the
amplifier and speaker in favor of a tiny magnet
mounted on a silicone disk, similar to a contact lens,
which rests right on the eardrum. Called the Earlens, it
is designed to be held in place by a thin film of oil.
Users wear a wireless microphone, either in the ear or
on a necklace, that picks up sounds and converts them
into magnetic signals, making the magnet vibrate. As
the Earlens vibrates, so does the eardrum, transmitting
normal-sounding tones to the middle and inner ears.
Other researchers are bypassing the middle ear
completely; they surgically implant a tiny magnet in
the inner ear. By attaching a magnet to the round
window, they open a second pathway to the inner
ear. An electromagnetic coil implanted in bone behind
the ear vibrates the implanted magnet. Unlike the
Earlens, this magnetic implant would not block the
normal hearing pathway.

KEY TERMS
Audiologist—A person with a degree and/or certification in the areas of identification and measurement of hearing impairments and rehabilitation of
those with hearing problems.
Eardrum—A paper-thin covering stretching across
the ear canal that separates the middle and outer
ears.
Middle ear—The small cavity between the eardrum and the oval window that houses the three
tiny bones of hearing.
Oval window—A tiny opening at the entrance to
the inner ear.

Aftercare
Preparation
The fist step in getting a hearing aid is to have a
medical exam and a hearing evaluation. (Most states
prohibit anyone selling a hearing aid until the patient
has been examined by a physician to rule out medical
problems.) After performing a hearing evaluation, an
audiologist should be able to determine whether a
hearing aid will help, and which one will do the most
good. This is especially important because aids can be
very expensive (between $500 and $4,000), and are
often not covered by health insurance. Hearing aids
come in a wide range of styles and types, requiring
careful testing to make sure the aid is the best choice
for a particular hearing loss.
Some audiologists sell aids; others can make a
recommendation, or give one a list of competent dealers in one’s area. Patients should shop around and
compare prices. In all but three states, hearing aids
must be fitted and sold only by licensed specialists
called dealers, specialists, dispensers, or dispensing
audiologists.
The hearing aid dealer will make an impression
of the consumer’s ears using a putty-like material,
from which a personalized earmold will be created.
It’s the dealer’s job to make sure the aid fits properly.
The person may need several visits to find the right
hearing aid and learn how to use it. The dealer will
help the consumer learn how to put the aid on, adjust
the controls, and maintain the device. The dealer
should be willing to service the aid and provide
information about what to do if sensitivity to the
earmold develops. (Some people are allergic to the
materials in the mold.)
1696

Within several weeks, the wearer should return to
the dealer to have the aid checked, and to discuss the
progress in wearing the aid. About 40% of all aids need
some modification or adjustment in the beginning.
Within the first month of getting an aid, the
patient should make an appointment for a full hearing
examination to determine if the aid is functioning
properly.

Risks
While there are no medical risks to hearing aids,
there is a risk associated with hearing aids: many
people end up not wearing their aids because they
say everything seems loud when wearing them. This
is because they have lived for so long with a hearing
problem that they have forgotten how loud ‘‘normal’’
sound can be. Other potential problems with hearing
aids include earmold discomfort, and a build up of
excess ear wax after getting a hearing aid.

Normal results
A hearing aid will boost the loudness of sound,
which can improve a person’s ability to understand
speech.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
Better Hearing Institute. 515 King Street, Suite 420,
Alexandria, VA 22314. (703) 684-3391.
GALE ENCYCLOPEDIA OF MEDICINE

Decibel Ratings And Hazardous Levels Of Noise

Carol A. Turkington

Decibel
Level

Example Of Sounds

30
35
40
50
60

Soft whisper
Noise may prevent the listener from falling asleep
Quiet office noise level
Quiet conversation
Average television volume, sewing machine, lively
conversation
Busy traffic, noisy restaurant
Heavy city traffic, factory noise, alarm clock
Cocktail party, lawn mower
Pneumatic drill
Sandblasting, thunder
Jet airplane
Rocket launching pad

70
80
90
100
120
140
180

Hearing loss

Above 110 decibels, hearing may become painful
Above 120 decibels is considered deafening
Above 135 decibels, hearing will become extremely painful and hearing loss
may result if exposure is prolonged Above 180 decibels, hearing loss is
almost certain with any exposure

Definition
Hearing loss is any degree of impairment of the
ability to apprehend sound.

Description
Sound can be measured accurately. The term decibel (dB) refers to an amount of energy moving sound
from its source to our ears or to a microphone. A drop
of more than 10 dB in the level of sound a person can
hear is significant.
Sound travels through a medium like air or water
as waves of compression and rarefaction. These waves
are collected by the external ear and cause the tympanic membrane (ear drum) to vibrate. The chain of
ossicles connected to the ear drum—the incus, malleus,
and stapes—carries the vibration to the oval window,
increasing its amplitude 20 times on the way. There the
energy causes a standing wave in the watery liquid
(endolymph) inside the Organ of Corti. (A standing
wave is one that does not move. A vibrating cup of
coffee will demonstrate standing waves.) The configuration of the standing wave is determined by the
frequency of the sound. Many thousands of tiny
nerve fibers detect the highs and lows of the standing
wave and transmit their findings to the brain, which
interprets the signals as sound.
To summarize, sound energy passes through the
air of the external ear, the bones of the middle ear and
the liquid of the inner ear. It is then translated into
nerve impulses, sent to the brain through nerves and
understood there as sound. It follows that there are
five steps in the hearing process:


air conduction through the external ear to the ear
drum

GALE ENCYCLOPEDIA OF MEDICINE

Hearing loss

Hearing Industries Association. 1800 M St. NW,
Washington, DC 20036. (202) 651-5258.
Hear Now. 9745 E. Hampden Ave., Ste. 300, Denver, CO
80231. (800) 648-HEAR. (202) 651-5258.
National Hearing Aid Society. 20361 Middlebelt, Livonia,
MI 48152. (800) 521-5247 or (313) 478-2610.
National Information Center on Deafness. Gallaudet
College, 800 Florida Ave. NE, Washington, DC 20002.
(202) 651-5051; (202) 651-5052 (TDD).



bone conduction through the middle ear to the inner
ear



water conduction to the Organ of Corti



nerve conduction into the brain



interpretation by the brain.

Hearing can be interrupted in several ways at each
of the five steps.
The external ear canal can be blocked with ear wax,
foreign objects, infection, and tumors. Overgrowth of
the bone, a condition that occurs when the ear canal has
been flushed with cold water repeatedly for years, can
also narrow the passageway, making blockage and
infection more likely. This condition occurs often in
Northern Californian surfers and is therefore called
‘‘surfer’s ear.’’
The ear drum is so thin a physician can see
through it into the middle ear. Sharp objects, pressure
from an infection in the middle ear, even a firm cuffing
or slapping of the ear, can rupture it. It is also susceptible to pressure changes during scuba diving.
Several conditions can diminish the mobility of the
ossicles (small bones) in the middle ear. Otitis media (an
infection in the middle ear) occurs when fluid cannot
escape into the throat because of blockage of the eustachian tube. The fluid that accumulates, whether it be
pus or just mucus and dampens the motion of the
ossicles. A disease called otosclerosis can bind the stapes
in the oval window and thereby cause deafness.
1697

Hearing loss
An Oto-Acoustic Emission (OAE) hearing test being perfomred on a newborn baby. The probe emits harmless sound into
the baby’s ear, and the response of the inner ear is detected and registered on a computer. Early diagnosis of a hearing disorder
is important in young children, who may experience difficulties in speech and language development. (Photograph by James
King-Holmes, Photo Researchers, Inc. Reproduced by permission.)

All the conditions mentioned so far, those that
occur in the external and middle ear, are causes of
conductive hearing loss. The second category, sensory
hearing loss, refers to damage to the Organ of Corti
and the acoustic nerve. Prolonged exposure to loud
noise is the leading cause of sensory hearing loss. A
million people have this condition, many identified
during the military draft and rejected as being unfit
for duty. The cause is often believed to be prolonged
exposure to rock music. Occupational noise exposure
is the other leading cause of noise induced hearing
loss (NIHL) and is ample reason for wearing ear protection on the job. A third of people over 65 have
presbycusis—sensory hearing loss due to aging. Both
NIHL and presbycusis are primarily high frequency
losses. In most languages, it is the high frequency
sounds that define speech, so these people hear plenty
of noise, they just cannot easily make out what it
means. They have particular trouble selecting out
speech from background noise. Brain infections like
meningitis, drugs such as the aminoglycoside antibiotics
(streptomycin, gentamycin, kanamycin, tobramycin),
1698

and Meniere’s disease also cause permanent sensory
hearing loss. Meniere’s disease combines attacks of
hearing loss with attacks of vertigo. The symptoms
may occur together or separately. High doses of salicylates like aspirin and quinine can cause a temporary
high-frequency loss. Prolonged high doses can lead to
permanent deafness. There is an hereditary form of
sensory deafness and a congenital form most often
caused by rubella (German measles).
Sudden hearing loss—at least 30dB in less than
three days—is most commonly caused by cochleitis, a
mysterious viral infection.
The final category of hearing loss is neural.
Damage to the acoustic nerve and the parts of the
brain that perform hearing are the most likely to produce permanent hearing loss. Strokes, multiple sclerosis, and acoustic neuromas are all possible causes of
neural hearing loss.
Hearing can also be diminished by extra sounds
generated by the ear, most of them from the same
kinds of disorders that cause diminished hearing.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
An examination of the ears and nose combined
with simple hearing tests done in the physician’s office
can detect many common causes of hearing loss. An
audiogram often concludes the evaluation, since these
simple means often produce a diagnosis. If the defect is
in the brain or the acoustic nerve, further neurological
testing and imaging will be required.
The audiogram has many uses in diagnosing
hearing deficits. The pattern of hearing loss across
the audible frequencies gives clues to the cause.
Several alterations in the testing procedure can
give additional information. For example, speech is
perceived differently than pure tones. Adequate perception of sound combined with inability to recognize words points to a brain problem rather than a
sensory or conductive deficit. Loudness perception
is distorted by disease in certain areas but not in
others. Acoustic neuromas often distort the perception of loudness.

Treatment
Conductive hearing loss can almost always be
restored to some degree, if not completely.


matter in the ear canal can be easily removed with a
dramatic improvement in hearing.



surfer’s ear gradually regresses if cold water is
avoided or a special ear plug is used. In advanced
cases, surgeons can grind away the excess bone.



middle ear infection with fluid is also simple to treat.
If medications do not work, surgical drainage of the
ear is accomplished through the ear drum, which
heals completely after treatment.



traumatically damaged ear drums can be repaired
with a tiny skin graft.



surgical repair of otosclerosis through an operating
microscope is one of the most intricate of procedures,
substituting tiny artificial parts for the original
ossicles.

Sensory and neural hearing loss, on the other
hand, cannot readily be cured. Fortunately it is not
often complete, so that hearing aids can fill the deficit.
In-the-ear hearing aids can boost the volume of
sound by up to 70 dB. (Normal speech is about 60 dB.)
Federal law now requires that they be dispensed only
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Decibel—A unit of the intensity of sound, a measure of loudness.
Meniere’s disease—The combination of vertigo
and decreased hearing caused by abnormalities in
the inner ear.
Multiple sclerosis—A progressive disease of brain
and nerve tissue.
Otosclerosis—A disease that scars and limits the
motion of the small conducting bones in the middle
ear.
Stroke—Sudden loss of blood supply to part of the
brain.

upon a physician’s prescription. For complete conduction hearing loss there are now available bone conduction hearing aids and even devices that can be
surgically implanted in the cochlea.
Tinnitus can sometimes be relieved by adding
white noise (like the sound of wind or waves crashing
on the shore) to the environment.
Decreased hearing is such a common problem
that there are legions of organizations to provide assistance. Special language training, both in lip reading
and signing, special schools and special camps for
children are all available in most regions of the
United States.

Alternative treatment
Conductive hearing loss can be treated with alternative therapies that are specific to the particular condition. Sensory hearing loss may be helped by
homeopathic therapies. Oral supplementation with
essential fatty acids such as flax oil and omega 3 oil
can help alleviate the accumulation of wax in the ear.

Prevention
Prompt treatment and attentive follow-up of middle ear infections in children will prevent this cause of
conductive hearing loss. Control of infectious childhood diseases such as measles has greatly reduced
sensory hearing loss as a complication of epidemic
diseases. Laws that require protection from loud
noise in the workplace have achieved substantial
reduction in noise induced hearing loss. Surfers should
use the right kind of ear plugs.
1699

Hearing loss

These sounds are referred to as tinnitus and can be
ringing, blowing, clicking, or anything else that no one
but the patient hears.

Hearing tests with a tuning fork

Precautions

Resources
ORGANIZATIONS

Alexander Graham Bell Association for the Deaf. 3417
Volta Place NW, Washington, DC 20007. (202)
337-5220. <http://www.agbell.org>.
Auditory-Verbal International. 2121 Eisenhower Ave.,
Suite 402, Alexandria, VA 22314. (703) 739-1049.
<avi@auditory-verbal.org> <http://www.
auditory-verbal.org/contact.htm>.
Better Hearing Institute. 515 King Street, Suite 420,
Alexandria, VA 22314. (703) 684-3391.
Central Institute for the Deaf. Washington University.
St. Louis, Missouri. <http://cidmac.wustl.edu>.
League for the Hard of Hearing. 71 West 23rd St., New
York, New York 10010-4162. (212) 741-7650.
<http://www.lhh.org>.
National Association of the Deaf. 814 Thayer Ave., Silver
Spring, MD, 20910. (301) 587-1788. <http://
nad.policy.net>.
Self Help for Hard of Hearing People, Inc. 7800 Wisconsin
Ave., Bethesda, MD 20814. (301) 657-2248.
<http://www.shhh.org>.
The Sight & Hearing Association (SHA).
<http://www.sightandhearing.org>.
World Recreation Association of the Deaf (WRAD).
<http://www.wrad.org>.

No special precautions are necessary when tuning
forks are used to conduct a hearing test.

Description
Two types of hearing tests with tuning forks are
typically conducted. In the Rinne test, the vibrating
tuning fork is held against the skull, usually on the
bone behind the ear (mastoid process) to cause vibrations through the bones of the skull and inner ear.
It is also held next to, but not touching, the ear, to
cause vibrations in the air next to the ear. The patient
is asked to determine which sound is louder, the sound
heard through the bone or through the air. A second
hearing test using a tuning fork is the Weber test. For
this test, the stem or handle of the vibrating tuning
fork is placed at various points along the midline of the
skull and face. The patient is then asked to identify
which ear hears the sound created by the vibrations.
Tuning forks of different sizes produce different
frequencies of vibrations and can be used to establish
the range of hearing for an individual patient.

Preparation
J. Ricker Polsdorfer, MD

Hearing test with an audiometer see
Audiometry

Hearing tests with a tuning
fork

No special preparation is required for a hearing
test with tuning forks.

Aftercare
No special aftercare is required. If hearing loss is
revealed during testing with tuning forks, the patient
may require further testing to determine the extent of
the hearing loss.

Risks
There are no risks associated with the use of tuning forks to screen for hearing loss.

Definition
A tuning fork is a metal instrument with a handle
and two prongs or tines. Tuning forks, made of steel,
aluminum, or magnesium-alloy will vibrate at a set
frequency to produce a musical tone when struck.
The vibrations produced can be used to assess a
person’s ability to hear various sound frequencies.

Purpose
A vibrating tuning fork held next to the ear or
placed against the skull will stimulate the inner ear
to vibrate, and can help determine if there is hearing loss.
1700

Normal results
With the Rinne test, a person will hear the tone
of the vibration longer and louder when the tuning
fork is held next to the ear, rather than when it is held
against the mastoid bone. For the Weber test, the tone
produced when the tuning fork is placed along the
center of the skull, or face, sounds about the same
volume in each ear.

Abnormal results
The Rinne test detects a hearing loss when a
patient hears a louder and longer tone when the
GALE ENCYCLOPEDIA OF MEDICINE

Mastoid process—The protrusions of bone behind
the ears at the base of the skull.
Rinne test—A hearing test using a vibrating tuning
fork which is held near the ear and held at the back
of the skull.
Weber test—A hearing test using a vibrating tuning
fork which is held at various points along the midline of the skull and face.

vibrating tuning fork is held against the mastoid bone
than when it is held next to the ear. The volume of
sound vibrations conducted through parts of the skull
and face in the Weber test can indicate which ear may
have a hearing loss.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA
22314-3357. (703) 836-4444. <http://
www.entnet.org>.
Ear Foundation. 1817 Patterson St., Nashville, TN 37203.
(800) 545-4327. <http://www.earfoundation.org>.

Altha Roberts Edgren

Heart arrest see Sudden cardiac death
Heart arrhythmias see Arrhythmias

Heart attack
Definition
A heart attack is the death of, or damage to, part
of the heart muscle because the supply of blood to the
heart muscle is severely reduced or stopped.

Description
Heart attack is the leading cause of death in
the United States. More than 1.5 million Americans
suffer a heart attack every year, and almost half a
million die, according to the American Heart
Association. Most heart attacks are the end result of
years of silent but progressive coronary artery disease,
which can be prevented in many people. A heart attack
GALE ENCYCLOPEDIA OF MEDICINE

often is the first symptom of coronary artery disease.
According to the American Heart Association, 63%
of women and 48% of men who died suddenly of
coronary artery disease had no previous symptoms.
Heart attacks also are called myocardial infarctions
(MIs).
A heart attack occurs when one or more of the
coronary arteries that supply blood to the heart are
completely blocked and blood to the heart muscle is
cut off. The blockage usually is caused by atherosclerosis, the build-up of plaque in the artery walls, and/or
by a blood clot in a coronary artery. Sometimes, a
healthy or atherosclerotic coronary artery has a
spasm and the blood flow to part of the heart
decreases or stops. Why this happens is unclear, but
it can result in a heart attack.
About half of all heart attack victims wait at least
two hours before seeking help. This increases their
chance of sudden death or being disabled. The longer
the artery remains blocked during a heart attack, the
more damage will be done to the heart. If the blood
supply is cut off severely or for a long time, muscle
cells suffer irreversible injury and die. This can cause
the patient to die. That is why it is important to
recognize the signs of a heart attack and seek prompt
medical attention at the nearest hospital with 24-hour
emergency cardiac care.
About one-fifth of all heart attacks are silent, that
is, the victim does not know one has occurred.
Although the victim feels no pain, silent heart attacks
still can damage the heart.
The outcome of a heart attack also depends on
where the blockage is, whether the heart rhythm is
disturbed, and whether another coronary artery supplies blood to that part of the heart. Blockages in the
left coronary artery usually are more serious than in
the right coronary artery. Blockages that cause an
arrhythmia, an irregular heartbeat, can cause sudden
death.

Causes and symptoms
Heart attacks generally are caused by severe
coronary artery disease. Most heart attacks are caused
by blood clots that form on atherosclerotic plaque.
This blocks a coronary artery from supplying oxygen-rich blood to part of the heart. A number of
major and contributing risk factors increase the risk
of developing coronary artery disease. Some of these
can be changed and some cannot. People with more
risk factors are more likely to develop coronary artery
disease.
1701

Heart attack

KEY TERMS

Heart attack

Major risk factors



Major risk factors significantly increase the risk
of coronary artery disease. Those which cannot be
changed are:


Heredity. People whose parents have coronary artery
disease are more likely to develop it. African
Americans also are at increased risk, due to their
higher rate of severe hypertension than whites.



Sex. Men under the age of 60 years of age are more
likely to have heart attacks than women of the
same age.



Age. Men over the age of 45 and women over the age
of 55 are considered at risk. Older people (those over
65) are more likely to die of a heart attack. Older
women are twice as likely to die within a few weeks of
a heart attack as a man. This may be because of other
co-existing medical problems.
Major risk factors that can be changed are:









Smoking. Smoking greatly increases both the chance
of developing coronary artery disease and the change
of dying from it. Smokers have two to four times the
risk of non-smokers of sudden cardiac death and are
more than twice as likely to have a heart attack. They
also are more likely to die within an hour of a heart
attack. Second-hand smoke also may increase risk.
High cholesterol. Cholesterol is a soft, waxy substance that is produced by the body, as well as
obtained from eating foods such as meat, eggs, and
other animal products. Cholesterol level is affected
by age, sex, heredity, and diet. Risk of developing
coronary artery disease increases as blood cholesterol levels increase. When combined with other factors, the risk is even greater. Total cholesterol of
240 mg/dL and over poses a high risk, and 200–239
mg/dL a borderline high risk. In LDL cholesterol,
high risk starts at 130–159 mg/dL, depending on
other risk factors. HDL (healthy cholesterol) can
lower or raise the coronary risk also.
High blood pressure. High blood pressure makes
the heart work harder, and over time, weakens it.
It increases the risk of heart attack, stroke, kidney
failure, and congestive heart failure. A blood pressure of 140 over 90 or above is considered high. As
the numbers increase, high blood pressure goes from
Stage 1 (mild) to Stage 4 (very severe). When combined with obesity, smoking, high cholesterol, or
diabetes, the risk of heart attack or stroke increases
several times.
Lack of physical activity. This increases the risk
of coronary artery disease. Even modest physical
activity is beneficial if done regularly.

1702

Use of certain drugs or supplements. Extreme caution is advised in the use of the herbal supplement
ephedra. The supplement, which was marketed for
weight loss and to improve athletic performance, was
found to contribute to heart attack, seizure, stoke
and death. In April 2003, the U.S. Food and Drug
Administration (FDA) investigating controlling or
banning the substance. While it was once believed
that hormone replacement therapy (HRT) helped
prevent heart disease in women, a large clinical
trial called the Women’s Health Initiative found
the opposite to be true. In 2003, the FDA began
requiring manufacturers of HRT to place warnings
on the box listing adverse effects of estrogen, including increased risk of heart attack, stroke and blood
clots. The labels also must mention that HRT should
not be used as a preventive medicine for heart disease.
Contributing risk factors

Contributing risk factors have been linked to coronary artery disease, but their significance or prevalence cannot always be demonstrated. Contributing
risk factors are:


Diabetes mellitus. The risk of developing coronary
artery disease is seriously increased for diabetics.
More than 80% of diabetics die of some type of
heart or blood vessel disease.



Obesity. Excess weight increases the strain on the
heart and increases the risk of developing coronary
artery disease, even if no other risk factors are present. Obesity increases both blood pressure and blood
cholesterol, and can lead to diabetes.



Stress and anger. Some scientists believe that stress
and anger can contribute to the development of coronary artery disease. Stress, the mental and physical
reaction to life’s irritations and challenges, increases
the heart rate and blood pressure, and can injure the
lining of the arteries. Evidence shows that anger
increases the risk of dying from heart disease and
more than doubles the risk of having a heart attack
right after an episode of anger.



Rheumatoid arthritis in women. A report released in
2003 noted that women with rheumatoid arthritis
has a higher risk of heart attach than those without
the condition. The reason is most likely the inflammation arthritis causes.

More than 60% of heart attack victims experience
symptoms before the heart attack occurs. These sometimes occur days or weeks before the heart attack.
Sometimes, people do not recognize the symptoms of
a heart attack or are in denial that they are having one.
Symptoms are:
GALE ENCYCLOPEDIA OF MEDICINE

Uncomfortable pressure, fullness, squeezing, or pain
in the center of the chest. This lasts more than a few
minutes, or may go away and return.



Pain that spreads to the shoulders, neck, or arms.



Chest discomfort accompanied by lightheadedness,
fainting, sweating, nausea, or shortness of breath.

All of these symptoms do not occur with every
heart attack. Sometimes, symptoms disappear and
then reappear. A person with any of these symptoms
should immediately call an emergency rescue service
or be driven to the nearest hospital with a 24-hour
cardiac care unit, whichever is quicker.

Diagnosis
Experienced emergency care personnel usually
can diagnose a heart attack simply by looking at the
patient. To confirm this diagnosis, they talk with the
patient, check heart rate and blood pressure, perform
an electrocardiogram, and take a blood sample. The
electrocardiogram shows which coronary artery is
blocked. Electrodes covered with conducting jelly are
placed on the patient’s chest, arms, and legs. They
send impulses of the heart’s activity through an oscilloscope (a monitor) to a recorder, which traces them
on paper. The blood test shows the leak of enzymes
or other biochemical markers from damaged cells in
the heart muscle. In 2003, the FDA cleared a new test
for ruling out heart attacks in people who come to
emergency rooms with severe chest pains. It is the first
new blood test for evaluation of heart attacks since
1994 and is used along with an electrocardiogram.

Treatment
Heart attacks are treated with cardiopulmonary
resuscitation (CPR) when necessary to start and keep
the patient breathing and his heart beating. Additional
treatment can include close monitoring, electric shock,
drug therapy, re-vascularization procedures, percutaneous transluminal coronary angioplasty and coronary
artery bypass surgery. Upon arrival at the hospital, the
patient is closely monitored. An electrical-shock device,
a defibrillator, may be used to restore a normal rhythm
if the heartbeat is fluttering uncontrollably. Oxygen
often is used to ease the heart’s workload or to help
victims of severe heart attack breathe easier. If oxygen
is used within hours of the heart attack, it may help
limit damage to the heart.
Drugs to stabilize the patient and limit damage to
the heart include thrombolytics, aspirin, anticoagulants, painkillers and tranquilizers, beta-blockers,
ace-inhibitors, nitrates, rhythm-stabilizing drugs, and
GALE ENCYCLOPEDIA OF MEDICINE

diuretics. Drugs that limit damage to the heart work
only if given within a few hours of the heart attack.
Thrombolytic drugs that break up blood clots
and enable oxygen-rich blood to flow through the
blocked artery increase the patient’s chance of survival if given as soon as possible after the heart attack.
Thrombolytics given within a few hours after a heart
attack are the most effective. Injected intravenously,
these include anisoylated plasminogen streptokinase
activator complex (APSAC) or anistreplase (Eminase),
recombinant tissue-type plasminogen activator (r-tPA,
Retevase, or Activase), and streptokinase (Streptase,
Kabikinase).
To prevent additional heart attacks, aspirin and
an anticoagulant drug often follow the thrombolytic
drug. These prevent new blood clots from forming and
existing blood clots from growing. Anticoagulant
drugs help prevent the blood from clotting. The most
common anticoagulants are heparin and warfarin.
Heparin is given intravenously while the patient is in
the hospital. Warfarin, taken orally, often is given
later. Aspirin helps to prevent the dissolved blood
clots from reforming.
To relieve pain, a nitroglycerine tablet taken
under the tongue may be given. If the pain continues,
morphine sulfate may be prescribed. Tranquilizers
such as diazepam (Valium) and alprazolam (Ativan)
may be prescribed to lessen the trauma of a heart
attack.
To slow down the heart rate and give the heart a
chance to heal, beta-blockers often are given intravenously right after the heart attack. These can also
help prevent sometimes fatal ventricular fibrillation.
Beta-blockers include atenolol (Tenormin), metoprolol
(Lopressor), nadolol, pindolol (Visken), propranolol
(Inderal), and timolol (Blocadren).
Nitrates, a type of vasodilator, also are given right
after a heart attack to help improve the delivery
of blood to the heart and ease heart failure symptoms.
Nitrates include isosorbide mononitrate (Imdur),
isosorbide dinitrate (Isordil, Sorbitrate), and nitroglycerin (Nitrostat).
When a heart attack causes an abnormal heartbeat, arrhythmia drugs may be given to restore
the heart’s normal rhythm. These include: amiodarone
(Cordarone), atropine, bretylium, disopyramide
(Norpace), lidocaine (Xylocaine), procainamide
(Procan), propafenone (Rythmol), propranolol
(Inderal), quinidine, and sotalol (Betapace).
Angiotensin-converting enzyme (ACE) inhibitors
reduce the resistance against which the heart beats
and are used to manage and prevent heart failure.
1703

Heart attack



Heart attack

They are used to treat heart attack patients whose
hearts do not pump well or who have symptoms of
heart failure. Taken orally, they include Altace,
Capoten, Lotensin, Monopril, Prinivil, Vasotec, and
Zestril. Angiotensin receptor blockers, such as losartan (Cozaar) may substitute. Diuretics can help
get rid of excess fluids that sometimes accumulate
when the heart is not pumping effectively. Usually
taken orally, they cause the body to dispose of fluids
through urination. Common diuretics include: bumetanide (Bumex), chlorthalidone (Hygroton), chlorothiazide (Diuril), furosemide (Lasix), hydrochlorothiazide
(HydroDIRUIL, Esidrix), spironolactone (Aldactone),
and triamterene (Dyrenium).
Percutaneous transluminal coronary angioplasty
and coronary artery bypass surgery are invasive revascularization procedures that open blocked coronary
arteries and improve blood flow. They usually are
performed only on patients for whom clot-dissolving
drugs do not work, or who have poor exercise stress
tests, poor left ventricular function, or ischemia.
Generally, angioplasty is performed before coronary
artery bypass surgery.
Percutaneous transluminal coronary angioplasty,
usually called coronary angioplasty, is a non-surgical
procedure in which a catheter (a tiny plastic tube)
tipped with a balloon is threaded from a blood vessel
in the thigh or arm into the blocked artery. The
balloon is inflated and compresses the plaque to
enlarge the blood vessel and open the blocked artery.
The balloon is then deflated and the catheter is
removed. Coronary angioplasty is performed in a hospital and generally requires a two-day stay. It is successful about 90% of the time. For one third of
patients, the artery narrows again within six months
after the procedure. The procedure can be repeated.
It is less invasive and less expensive than coronary
artery bypass surgery.
In coronary artery bypass surgery, called bypass
surgery, a detour is built around the coronary artery
blockage with a healthy leg or chest wall artery or vein.
The healthy vein then supplies oxygen-rich blood to
the heart. Bypass surgery is major surgery appropriate
for patients with blockages in two or three major
coronary arteries or severely narrowed left main coronary arteries, as well as those who have not
responded to other treatments. It is performed in a
hospital under general anesthesia using a heart-lung
machine to support the patient while the healthy vein
is attached to the coronary artery. About 70% of
patients who have bypass surgery experience full relief
from angina; about 20% experience partial relief.
Long term, symptoms recur in only about three or
1704

four percent of patients per year. Five years after
bypass surgery, survival expectancy is 90%, at 10
years it is about 80%, at 15 years it is about 55%,
and at 20 years it is about 40%.
There are several experimental surgical procedures for unblocking coronary arteries under study
including: atherectomy, where the surgeon shaves
off and removes strips of plaque from the blocked
artery; laser angioplasty, where a catheter with a
laser tip is inserted to burn or break down the plaque;
and insertion of a metal coil called a stent that can be
implanted permanently to keep a blocked artery open.

Prognosis
The aftermath of a heart attack is often severe.
Two-thirds of heart attack patients never recover
fully. Within one year, 27% of men and 44% of
women die. Within six years, 23% of men and 31%
of women have another heart attack, 13% of men and
6% of women experience sudden death, and about
20% have heart failure. People who survive a heart
attack have a chance of sudden death that is four to six
times greater than others and a chance of illness and
death that is two to nine times greater. Older women
are more likely than men to die within a few weeks of a
heart attack. In 2003, a new drug showed some promise in helping patients who have had a heart attack
and developed heart failure. Called eplerenone, it lowered the death rate and risk of sudden death among
patients tested.

Prevention
Many heart attacks can be prevented through a
healthy lifestyle, which can reduce the risk of developing coronary artery disease. For patients who have
already had a heart attack, a healthy lifestyle and
carefully following doctor’s orders can prevent
another heart attack. A heart healthy lifestyle
includes eating right, regular exercise, maintaining a
healthy weight, no smoking, moderate drinking, no
illegal drugs, controlling hypertension, and managing stress.
A healthy diet includes a variety of foods that are
low in fat (especially saturated fat), low in cholesterol,
and high in fiber; plenty of fruits and vegetables; and
limited sodium. Some foods are low in fat but high in
cholesterol, and some are low in cholesterol but high in
fat. Saturated fat raises cholesterol, and, in excessive
amounts, it increases the amount of the proteins in
blood that form blood clots. Polyunsaturated and
monounsaturated fats are relatively good for the
GALE ENCYCLOPEDIA OF MEDICINE

Cholesterol, a waxy, lipid-like substance, comes
from eating foods such as meat, eggs, and other animal
products. It also is produced in the liver. Soluble fiber
can help lower cholesterol. Cholesterol should be
limited to about 300 mg per day. Many popular
lipid-lowering drugs can reduce LDL-cholesterol by
an average of 25–30% when combined with a low-fat,
low-cholesterol diet. Fruits and vegetables are rich in
fiber, vitamins, and minerals. They are also low calorie
and nearly fat free. Vitamin C and beta-carotene,
found in many fruits and vegetables, keep LDLcholesterol from turning into a form that damages
coronary arteries. Excess sodium can increase the
risk of high blood pressure. Many processed foods
contain large amounts of sodium, which should be
limited to a daily intake of 2,400 mg—about the
amount in a teaspoon of salt.
The ‘‘Food Guide’’ Pyramid developed by the
U.S. Departments of Agriculture and Health and
Human Services provides easy to follow guidelines
for daily heart-healthy eating: six to 11 servings of
bread, cereal, rice, and pasta; three to five servings of
vegetables; two to four servings of fruit; two to three
servings of milk, yogurt, and cheese; and two to three
servings of meat, poultry, fish, dry beans, eggs, and
nuts. Fats, oils, and sweets should be used sparingly.
Regular aerobic exercise can lower blood pressure, help control weight, and increase HDL
(‘‘good’’) cholesterol. It may keep the blood vessels
more flexible. Moderate intensity aerobic exercise lasting about 30 minutes four or more times per week is
recommended for maximum heart health, according
to the Centers for Disease Control and Prevention
and the American College of Sports Medicine. Three
10-minute exercise periods also are beneficial. Aerobic
exercise—activities such as walking, jogging, and
cycling—uses the large muscle groups and forces the
body to use oxygen more efficiently. It also can include
everyday activities such as active gardening, climbing
stairs, or brisk housework.
Maintaining a desirable body weight also is
important. About one-fourth of all Americans are
overweight, and nearly one-tenth are obese, according
to the Surgeon General’s Report on Nutrition and
Health. People who are 20% or more over their ideal
body weight have an increased risk of developing coronary artery disease. Losing weight can help reduce
total and LDL cholesterol, reduce triglycerides, and
boost relative levels of HDL cholesterol. It also may
reduce blood pressure.
GALE ENCYCLOPEDIA OF MEDICINE

Smoking has many adverse effects on the heart.
It increases the heart rate, constricts major arteries,
and can create irregular heartbeats. It also raises blood
pressure, contributes to the development of plaque,
increases the formation of blood clots, and causes
blood platelets to cluster and impede blood flow.
Heart damage caused by smoking can be repaired by
quitting–even heavy smokers can return to heart
health. Several studies have shown that ex-smokers
face the same risk of heart disease as non-smokers
within five to 10 years of quitting.
Drinking should be done in moderation. Modest
consumption of alcohol can actually protect against
coronary artery disease. This is believed to be because
alcohol raises HDL cholesterol levels. The American
Heart Association defines moderate consumption as
one ounce of alcohol per day—roughly one cocktail,
one 8-ounce glass of wine, or two 12-ounce glasses of
beer. A study released in 2003 reported that risk of
heart attack in men was reduced 30% to 35 % if they
drank moderate amounts of alcoholic beverages three
or four times a week. In some people, however, moderate drinking can increase risk factors for heart disease, such as raising blood pressure. Excessive
drinking is always bad for the heart. It usually raises
blood pressure, and can poison the heart and cause
abnormal heart rhythms or even heart failure. Illegal
drugs, like cocaine, can seriously harm the heart and
should never be used.
High blood pressure, one of the most common
and serious risk factors for coronary artery disease,
can be completely controlled through lifestyle
changes and medication. People with moderate
hypertension may be able to control it through
lifestyle changes such as reducing sodium and fat,
exercising regularly, managing stress, quitting smoking, and drinking alcohol in moderation. If these
changes do not work, and for people with severe
hypertension, there are eight types of drugs that
provide effective treatment.
Stress management means controlling mental
and physical reactions to life’s irritations and
challenges. Techniques for controlling stress
include: taking life more slowly, spending time
with family and friends, thinking positively, getting
enough sleep, exercising, and practicing relaxation
techniques.
Daily aspirin therapy has been proven to help
prevent blood clots associated with atherosclerosis.
It also can prevent heart attacks from recurring, prevent heart attacks from being fatal, and lower the risk
of strokes.
1705

Heart attack

heart. Fat should comprise no more than 30 percent of
total daily calories.

Heart block

KEY TERMS

Heart block

Angina—Chest pain that happens when diseased
blood vessels restrict the flow of blood to the heart.
Angina often is the first symptom of coronary artery
disease.
Atherosclerosis—A process in which the walls of
the coronary arteries thicken due to the accumulation of plaque in the blood vessels. Atherosclerosis
is the cause of coronary artery disease.
Coronary arteries—The two arteries that provide
blood to the heart. The coronary arteries surround
the heart like a crown, coming out of the aorta,
arching down over the top of the heart, and dividing into two branches. These are the arteries where
coronary artery disease occurs.
Myocardial infarction—The technical term for
heart attack. Myocardial means heart muscle and
infarction means death of tissue from lack of oxygen.
Plaque—A deposit of fatty and other substances
that accumulate in the lining of the artery wall.

Resources
PERIODICALS

‘‘First New Blood Test to Evaluate Heart Attacks.’’ Biomedical
Market Newsletter January-February 2003: 42.
‘‘Heart Attacks Reduced by Alchohol.’’ The Lancet
January 11, 2003: 149.
Kirn, Timothy F. ‘‘FDA Probes Ephedra, Proposes
Warning Label (Risk of Heart Attack, Seizure,
Stroke).’’ Clinical Psychiatry News April 2003: 49.
Pitt, Bertram, et al. ‘‘Eplerenone, a Selective Aldosterone
Blocker, in Patients with Left Ventricular Dysfunction
after Myocardial Infarction.’’ The New England
Journal of Medicine April 3, 2003: 1309-1313.
Stephenson, Joan. ‘‘FDA Orders Estrogen Safety Warnings:
Agency Offers Guidance for HRT Use.’’ JAMA
February 5, 2003: 537.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto
Teresa G. Odle
1706

Definition
Heart block refers to a delay in the normal flow of
electrical impulses that cause the heart to beat. They
are further classified as first-, second-, or third-degree
block.

Description
The muscles of the heart contract in a rhythmic
order for each heart beat, because electrical impulses
travel along a specific route called the conduction
system. The main junction of this system is called the
atrioventricular node (AV node). Just as on a highway, there are occasionally some delays getting the
impulse from one point to another. These delays are
classified according to their severity.
In first-degree heart block, the signal is just slowed
down a little as it travels along the defective part of the
conduction system so that it arrives late traveling from
the atrium to the ventricle.
In second-degree heart block, not every impulse
reaches its destination. The block may affect every
other beat, every second or third beat, or be very
rare. If the blockage is frequent, it results in an overall
slowing of the heart called bradycardia.
Third-degree block, also called complete heart
block, is the most serious. When no signals can travel
through the AV node, the heart uses its backup
impulse generator in the lower portion of the heart.
Though this impulse usually keeps the heart from
stopping entirely, it is too slow to be an effective pump.

Causes and symptoms
First-degree heart block is fairly common. It is
seen in teenagers, young adults and in well-trained
athletes. The condition may be caused by rheumatic
fever, some types of heart disease and by some drugs.
First-degree heart block produces no symptoms.
Some cases of second-degree heart block may
benefit from an artificial pace-maker. Second-degree
block can occasionally progress to third-degree.
Third-degree heart block is a serious condition
that affects the heart’s ability to pump blood effectively. Symptoms include fainting, dizziness and
sudden heart failure. If the ventricles beat more than
40 times per minute, symptoms are not as severe, but
include tiredness, low blood pressure on standing, and
shortness of breath.
GALE ENCYCLOPEDIA OF MEDICINE

Atrioventricular node (AV node)—Highly specialized area of the heart muscle which transmits
electrical impulses.
Bradycardia—A slow heart rate, usually under 60
beats per minute.

Young children who have received a forceful
blunt chest injury, can experience first-, or seconddegree heart block.

Diagnosis
Diagnosis of first-, and second-degree heart block
is made by observing it on an electrocardiograph
(ECG).
Third-degree heart block usually results in symptoms such as fainting, dizziness and sudden heart
failure, which require immediate medical care. A physical exam and ECG confirm the presence of heart
block.

Treatment
Some second- and almost all third-degree heart
blocks require an artificial pacemaker. In an emergency, a temporary pacemaker can be used until an
implanted device is advisable. Most people need the
pacemaker for the rest of their lives.

Prognosis
Most people with first- and second-degree heart
block don’t even know they have it. For people with
third-degree block, once the heart has been restored to
its normal, dependable rhythm, most people live full
and comfortable lives.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dorothy Elinor Stonely

Heart catheterization see Cardiac
catheterization
GALE ENCYCLOPEDIA OF MEDICINE

Heart failure
Definition
Heart failure is a condition in which the heart has
lost the ability to pump enough blood to the body’s
tissues. With too little blood being delivered, the
organs and other tissues do not receive enough oxygen
and nutrients to function properly.

Description
According to the American Heart Association,
about 4.9 million Americans are living with congestive
heart failure. Of these, 2.5 million are males and 2.4
million are females. Ten of every 1,000 people over age
65 have this condition. There are about 400,000 new
cases each year.
Heart failure happens when a disease affects the
heart’s ability to deliver enough blood to the body’s
tissues. Often, a person with heart failure may have a
buildup of fluid in the tissues, called edema. Heart
failure with this kind of fluid buildup is called congestive heart failure. Where edema occurs in the body
depends on the part of the heart that is affected by
heart failure. Heart failure caused by abnormality of
the lower left chamber of the heart (left ventricle)
means that the left ventricle cannot pump blood out
to the body as fast as it returns from the lungs. Because
blood cannot get back to the heart, it begins to back
up in the blood vessels of the lungs. Some of the fluid
in the blood is forced into the breathing space of
the lungs, causing pulmonary edema. A person with
pulmonary edema has shortness of breath, which may
be acute, severe and life threatening. A person with
congestive heart failure feels tired because not enough
blood circulates to supply the body’s tissues with the
oxygen and nutrients they need. Abnormalities of the
heart structure and rhythm also can be responsible
for left ventricular congestive heart failure.
In right-sided heart failure, the lower right chamber of the heart (right ventricle) cannot pump blood
to the lungs as fast as it returns from the body through
the veins. Blood then engorges the right side of the
heart and the veins. Fluid backed up in the veins is
forced out into the tissues, causing swelling (edema),
usually in the feet and legs. Congestive heart failure of
the right ventricle often is caused by abnormalities of
the heart valves and lung disorders.
When the heart cannot pump enough blood, it
tries to make up for this by becoming larger. By
becoming enlarged (hypertrophic) the ventricle can
1707

Heart failure

KEY TERMS

Heart failure

contract more strongly and pump more blood. When
this happens, the heart chamber becomes larger and
the muscle in the heart wall becomes thicker. The heart
also compensates by pumping more often to improve
blood output and circulation. The kidneys try to
compensate for a failing heart by retaining more salt
and water to increase the volume of blood. This extra
fluid also can cause edema. Eventually, as the condition worsens over time these measures are not enough
to keep the heart pumping enough blood needed
by the body. Kidneys often weaken under these circumstances, further aggravating the situation and
making therapy more difficult.
For most people, heart failure is a chronic disease
with no cure. However, it can be managed and treated
with medicines and changes in diet, exercise, and lifestyle habits. Heart transplantation is considered in
some cases.

Causes and symptoms
The most common causes of heart failure are:

cannot keep up and the symptoms of heart failure
develop.
Defects of the heart valves, congenital heart diseases, alcoholism, and drug abuse cause damage to the
heart that can all lead to heart failure.
A person with heart failure may experience the
following:


shortness of breath



frequent coughing, especially when lying down



swollen feet, ankles, and legs



abdominal swelling and pain



fatigue



dizziness or fainting



sudden death

A person with left-sided heart failure may have
shortness of breath and coughing caused by the fluid
buildup in the lungs. Pulmonary edema may cause the
person to cough up bubbly phlegm that contains
blood. With right-sided heart failure, fluid build-up
in the veins and body tissues causes swelling in the feet,
legs, and abdomen. When body tissues, such as organs
and muscles, do not receive enough oxygen and nutrients they cannot function as well, leading to tiredness
and dizziness.



coronary artery disease and heart attack (which may
be ‘‘silent’’)



cardiomyopathy



high blood pressure (hypertension)



heart valve disease

Diagnosis



congenital heart disease

Diagnosis of heart failure is based on:



alcoholism and drug abuse

The most common cause of heart failure is coronary artery disease. In coronary artery disease, the
arteries supplying blood to the heart become narrowed
or blocked. When blood flow to an area of the heart is
completely blocked, the person has a heart attack.
Some heart attacks go unrecognized. The heart muscle
suffers damage when its blood supply is reduced or
blocked. If the damage affects the heart’s ability to
pump blood, heart failure develops.
Cardiomyopathy is a general term for disease of
the heart muscle. Cardiomyopathy may be caused by
coronary artery disease and various other heart problems. Sometimes the cause of cardiomyopathy cannot
be found. In these cases the heart muscle disease is
called idiopathic cardiomyopathy. Whatever the
cause, cardiomyopathy can weaken the heart, leading
to heart failure.
High blood pressure is another common cause of
heart failure. High blood pressure makes the heart
work harder to pump blood. After a while, the heart
1708



symptoms



medical history



physical examination



chest x ray



electrocardiogram (ECG; also called EKG)



other imaging tests



cardiac catheterization

A person’s symptoms can provide important clues
to the presence of heart failure. Shortness of breath
while engaging in activities and episodes of shortness
of breath that wake a person from sleep are classic
symptoms of heart failure. During the physical examination, the physician listens to the heart and lungs
with a stethoscope for telltale signs of heart failure.
Irregular heart sounds, ‘‘gallops,’’ a rapid heart rate,
and murmurs of the heart valves may be heard. If there
is fluid in the lungs a crackling sound may be heard.
Rapid breathing or other changes in breathing may
also be present. Patients with heart failure also may
have a rapid pulse.
GALE ENCYCLOPEDIA OF MEDICINE

A chest x ray can show if there is fluid in the lungs
and if the heart is enlarged. Abnormalities of heart
valves and other structures also may be seen on chest
x ray.
An electrocardiogram gives information on the
heart rhythm and the size of the heart. It can show if
the heart chamber is enlarged and if there is damage to
the heart muscle from blocked arteries.
Besides chest x ray, other imaging tests may help
make a diagnosis. Echocardiography uses sound waves
to make images of the heart. These images can show
if the heart wall or chambers are enlarged and if there
are any abnormalities of the heart valves. An echocardiogram also can be used to find out how much blood
the heart is pumping. It determines the amount of
blood in the ventricle (ventricular volume) and the
amount of blood the ventricle pumps each time it
beats (called the ejection fraction). A healthy heart
pumps at least one-half the amount of blood in the
left ventricle with each heartbeat. Radionuclide ventriculography also measures the ejection fraction by
imaging with very low doses of an injected radioactive
substance as it travels through the heart.
A new test that measures the level of a particular
hormone in the blood was introduced in 2003 and
researchers said the test may be useful for testing for
heart failure in physicians’ offices because it could
provide results in 15 minutes.
Cardiac catheterization involves using a small
tube (catheter) that is inserted through a blood vessel
into the heart. It is used to measure pressure in the
heart and the amount of blood pumped by the heart.
This test can help find abnormalities of the coronary
arteries, heart valves, and heart muscle, and other
blood vessels. Combined with echocardiography and
other tests, cardiac catheterization can help find the
cause of heart failure. It is not always necessary,
however.

Treatment
Heart failure usually is treated with lifestyle
changes and medicines. Sometimes surgery is needed
to correct abnormalities of the heart or heart valves.
Heart transplantation is a last resort to be considered
in certain cases.
Dietary changes to maintain proper weight and
reduce salt intake may be needed. Reducing salt intake
GALE ENCYCLOPEDIA OF MEDICINE

helps to lessen swelling in the legs, feet, and abdomen.
Appropriate exercise also may be recommended, but it
is important that heart failure patients only begin an
exercise program with the advice of their doctors.
Walking, bicycling, swimming, or low-impact aerobic
exercises may be recommended. There are good heart
rehabilitation programs at most larger hospitals.
Other lifestyle changes that may reduce the symptoms of heart failure include stopping smoking or
other tobacco use, eliminating or reducing alcohol
consumption, and not using harmful drugs.
One or more of the following types of medicines
may be prescribed for heart failure:


diuretics



digitalis



vasodilators



beta blockers



angiotensin converting enzyme inhibitors (ACE
inhibitors)



angiotensin receptor blockers (ARBs)



calcium channel blockers

Diuretics help eliminate excess salt and water
from the kidneys by making patients urinate more
often. This helps reduce the swelling caused by fluid
buildup in the tissues. Digitalis helps the heart muscle
to have stronger pumping action. Vasodilators, ACE
inhibitors, ARBs, and calcium channel blockers lower
blood pressure and expand the blood vessels so blood
can move more easily through them. This action
makes it easier for the heart to pump blood through
the vessels. Cholesterol-lowering drugs called statins
can help prevent death from heart failure. A 2003
study showed a 62% drop in mortality rate among
patients with severe heart failure who took statin
therapy.
In 2003, a new noninvasive procedure was being
tested for patients with congestive heart failure. Called
enhanced external counterpulsation (EECP), it consisted of inflating three sets of pneumatic cuffs
attached to the patient’s legs. The therapy had positive
effects on the blood pressure and reduced frequency of
episodes of angina (pain) in a clinical trial by as much
as 70%.
Surgery is used to correct certain heart conditions
that cause heart failure. Congenital heart defects and
abnormal heart valves can be repaired with surgery.
Blocked coronary arteries usually can be treated with
angioplasty or coronary artery bypass surgery.
1709

Heart failure

By pressing on the abdomen, the physician can
feel if the liver is enlarged. The skin of the fingers and
toes may have a bluish tint and feel cool if not enough
oxygen is reaching them.

Heart failure

KEY TERMS
Angioplasty—A technique for treating blocked coronary arteries by inserting a catheter with a tiny
balloon at the tip into the artery and inflating it.
Angiotensin-converting enzyme (ACE) inhibitor—A
drug that relaxes blood vessel walls and lowers
blood pressure.
Arrhythmias—Abnormal heartbeat.
Atherosclerosis—Buildup of a fatty substance called
a plaque inside blood vessels.
Calcium channel blocker—A drug that relaxes blood
vessels and lowers blood pressure.
Cardiac catheterization—A diagnostic test for evaluating heart disease; a catheter is inserted into an
artery and passed into the heart.
Cardiomyopathy—Disease of the heart muscle.
Catheter—A thin, hollow tube.
Congenital heart defects—Abnormal formation of
structures of the heart or of its major blood vessels
present at birth.
Congestive heart failure—A condition in which the
heart cannot pump enough blood to supply the
body’s tissues with sufficient oxygen and nutrients;
back up of blood in vessels and the lungs causes
buildup of fluid (congestion) in the tissues.

With severe heart failure, the heart muscle may
become so damaged that available treatments do
not help. Patients with this stage of heart failure are
said to have end-stage heart failure. Heart transplant
usually is considered for patients with end-stage heart
failure when all other treatments have stopped
working.

Prognosis
Most patients with mild or moderate heart failure can be successfully treated with dietary and
exercise programs and the right medications. In
fact, in 2003, the American Heart Association said
that even those awaiting heart transplants could
benefit from exercise. Many people are able to participate in normal daily activities and lead relatively
active lives.
Patients with severe heart failure may eventually
have to consider heart transplantation. Approximately
50% of patients diagnosed with congestive heart
1710

Coronary arteries—Arteries that supply blood to the
heart muscle.
Coronary artery bypass—Surgical procedure to
reroute blood around a blocked coronary artery.
Coronary artery disease—Narrowing or blockage of
coronary arteries by atherosclerosis.
Digitalis—A drug that helps the heart muscle to have
stronger pumping action.
Diuretic—A type of drug that helps the kidneys eliminate excess salt and water.
Edema—Swelling caused by fluid buildup in tissues.
Ejection fraction—A measure of the portion of blood
that is pumped out of a filled ventricle.
Heart valves—Valves that regulate blood flow into
and out of the heart chambers.
Hypertension—High blood pressure.
Hypertrophic—Enlarged.
Idiopathic cardiomyopathy—Cardiomyopathy without a known cause.
Pulmonary edema—Buildup of fluid in the tissue of
the lungs.
Vasodilator—Any drug that relaxes blood vessel walls.
Ventricles—The two lower chambers of the heart.

failure live for five years with the condition. Women
with heart failure usually live longer than men with
heart failure.

Prevention
Heart failure usually is caused by the effects of
some type of heart disease. The best way to try to
prevent heart failure is to eat a healthy diet and get
regular exercise, but many causes of heart failure
cannot be prevented. People with risk factors for coronary disease (such as high blood pressure and high
cholesterol levels) should work closely with their physician to reduce likelihood of heart attack and heart
failure.
Heart failure sometimes can be avoided by identifying and treating any conditions that might lead to
heart disease. These include high blood pressure, alcoholism, and coronary artery disease. Regular blood
pressure checks and obtaining immediate medical
care for symptoms of coronary artery disease, such
GALE ENCYCLOPEDIA OF MEDICINE

A 2003 initiative called OPTIMIZE H-F was
aimed at preventing severe heart failure and deaths
among patients discharge from hospitals. The project
created a registry or database of patients with heart
failure that could be shared among hospitals. Finally,
diagnosing and treating heart failure before the heart
becomes severely damaged can improve the prognosis.
With proper treatment, many patients may continue
to lead active lives for a number of years.
Resources
PERIODICALS

‘‘Even Heart Failure Patients Should Exercise.’’ Clinician
Reviews April 2003: 50-52.
Jancin, Bruce. ‘‘Noninvasive Procedure Eyed for Heart
Failure: Enhanced External Counterpulsation.’’
Family Practice News June 1, 2003: 12.
‘‘New Care Initiative to Improve Outcomes for Heart
Failure Patients.’’ Heart Disease Weekly April 20,
2003: 45.
‘‘Rapid Congestive Heart Failure Test a Useful Tool in
Physician Offices.’’ Heart Disease Weekly June 15,
2003: 19.
Zoler, Michael N. ‘‘Heart Failure Deaths Plunge with
Statins.’’ Internal Medicine News April 15, 2003: 35-41.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Toni Rizzo
Teresa G. Odle

Heart murmurs
Definition
A heart murmur is an abnormal, extra sound
during the heartbeat cycle made by blood moving
through the heart and its valves. It is detected by the
physician’s examination using a stethoscope.
GALE ENCYCLOPEDIA OF MEDICINE

Description
A heart which is beating normal makes two
sounds, ‘‘lubb’’ when the valves between the atria
and ventricles close, and ‘‘dupp’’ when the valves
between the ventricles and the major arteries close. A
heart murmur is a series of vibratory sounds made by
turbulent blood flow. The sounds are longer than
normal heart sounds and can be heard between the
normal sounds of the heart.
Heart murmurs are common in children and can
also result from heart or valve defects. Nearly two
thirds of heart murmurs in children are produced by
a normal heart and are harmless. This type of heart
murmur is usually called an ‘‘innocent’’ heart murmur. It can also be called ‘‘functional’’ or ‘‘physiologic.’’ Innocent heart murmurs are usually very faint,
intermittent, and occur in a small area of the chest.
Pathologic heart murmurs may indicate the presence
of a serious heart defect. They are louder, continual,
and may be accompanied by a click or gallop.
Some heart murmurs are continually present;
others happen only when the heart is working harder
than usual, including during exercise or certain types
of illness. Heart murmurs can be diastolic or systolic.
Those which occur during relaxation of the heart
between beats are called diastolic murmurs. Those
which occur during contraction of the heart muscle
are called systolic murmurs. The characteristics of the
murmur may suggest specific alterations in the heart
or its valves.

Causes and symptoms
Innocent heart murmurs are caused by blood
flowing through the chambers and valves of the heart
or the blood vessels near the heart. Sometimes anxiety,
stress, fever, anemia, overactive thyroid, and pregnancy will cause innocent murmurs that can be heard
by a physician using a stethoscope. Pathologic heart
murmurs, however, are caused by structural abnormalities of the heart. These include defective heart
valves or holes in the walls of the heart. Valve problems
are more common. Valves that do not open completely
cause blood to flow through a smaller opening than
normal, while those that do not close properly may
cause blood to go back through the valve. A hole in
the wall between the left and right sides of the heart,
called a septal defect, can cause heart murmurs. Some
septal defects close on their own; others require surgery to prevent progressive damage to the heart.
The symptoms of heart murmurs differ depending
on the cause of the heart murmur. Innocent heart
1711

Heart murmurs

as chest pain, will help to get these conditions found
and treated early, before they can damage the heart
muscle.

Heart murmurs

murmurs and those which do not impair the function
of the heart have no symptoms. Murmurs that are due
to severe abnormalities of a heart valve may cause
shortness of breath, dizziness, chest pains, palpitations,
and lung congestion.

Diagnosis
Heart murmurs can be heard when a physician
listens to the heart through a stethoscope during a
regular check-up. Very loud heart murmurs and
those with clicks or extra heart sounds should be
evaluated further. Infants with heart murmurs who
do not thrive, eat, or breath properly and older children who lose consciousness suddenly or are intolerant to exercise should also be evaluated. If the murmur
sounds suspicious, the physician may order a chest
x ray, an electrocardiogram, and an echocardiogram.
An electrocardiogram (ECG) shows the heart’s
activity and may reveal muscle thickening, damage,
or a lack of oxygen. Electrodes covered with conducting jelly are placed on the patient’s chest, arms, and
legs. They send impulses of the heart’s activity through
a monitor (oscilloscope) to a recorder which traces
them on paper. The test takes about 10 minutes and
is commonly performed in a physician’s office. An
exercise ECG can reveal additional information.
An echocardiogram (cardiac ultrasound), may be
ordered to identify a structural problem that is causing
the heart murmur. An echocardiogram uses sound
waves to create an image of the heart’s chambers and
valves. The technician applies gel to a hand-held transducer then presses it against the patient’s chest. The
sound waves are converted into an image that can be
displayed on a monitor. Performed in a cardiology
outpatient diagnostic laboratory, the test takes 30
minutes to an hour.

Treatment
Innocent heart murmurs do not affect the patient’s
health and require no treatment. Heart murmurs due to
septal defects may require surgery. Those due to valvular defects may require antibiotics to prevent infection
during certain surgical or dental procedures. Severely
damaged or diseased valves can be repaired or replaced
through surgery.

KEY TERMS
Atria—The upper two chambers of the heart.
Echocardiogram—A non-invasive ultrasound test
that shows an image of the inside of the heart. An
echocardiogram can be performed to identify any
structural problems which cause a heart murmur.
Electrocardiogram—A test that shows the electrical activity of the heart by placing electronic sensors on the patient. This test can be used to confirm
the presence of a heart murmur.
Pathologic—Characterized by disease or the structural and functional changes due to disease.
Pathologic heart murmurs may indicate a heart
defect.
Ventricles—The lower two chambers of the heart.

post-surgical support of the patient. If the heart murmur is innocent, heart activity can be supported using
the herb hawthorn (Crataegus laevigata or C. oxyacantha) or coenzyme Q10. These remedies improve
heart contractility and the heart’s ability to use oxygen. If the murmur is valvular in origin, herbs that act
like antibiotics as well as options that build resistance
to infection in the valve areas may be considered.

Prognosis
Most children with innocent heart murmurs grow
out of them by the time they reach adulthood. Severe
causes of heart murmurs may progress to severe symptoms and death.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto

Heart muscle infection see Myocarditis
Alternative treatment
If a heart murmur requires surgical treatment,
there are no alternative treatments, although there
are alternative therapies that are helpful for pre- and
1712

Heart scan see Echocardiography
Heart septal defect see Atrial septal defect
Heart sonogram see Echocardiography
GALE ENCYCLOPEDIA OF MEDICINE

Definition
A variety of surgical procedures that are performed to repair the many types of heart defects that
may be present at birth.

Purpose
Heart surgery for congenital defects is performed
to repair a defect as much as possible and improve the
flow of blood and oxygen to the body. While congenital heart defects vary in their severity, most require
surgery. Surgery is recommended for congenital heart
defects that result in a lack of oxygen, a poor quality of
life, or a patient who does not thrive. Some types of
congenital heart defects that don’t cause symptoms
are treated surgically because they can lead to serious
complications.

Precautions
There are many types of surgery for congenital
heart defects and many considerations in the decision
to operate. The patient’s cardiologist or surgeon will
discuss these issues on an individual basis.

Description
There are many types of congenital heart
defects. Most obstruct the flow of blood in the
heart, or the vessels near it, or cause an abnormal
flow of blood through the heart. Rarer types include
newborns born with one ventricle, one side of the
heart that is not completely formed, or the pulmonary artery and the aorta coming out of the same
ventricle. Most congenital heart defects require surgery during infancy or childhood. Recommended
ages for surgery for the most common congenital
heart defects are:


atrial septal defects: during the preschool years



patent ductus arteriosus: between ages one and two



coarctation of the aorta: in infancy, if it’s symptomatic, at age four otherwise



tetralogy of Fallot: age varies, depending on the
patient’s signs and symptoms



transposition of the great arteries: often in the
first weeks after birth, but before the patient is
12 months old

GALE ENCYCLOPEDIA OF MEDICINE

Surgical procedures seek to repair the defect as
much as possible and restore circulation to as close to
normal as possible. Sometimes, multiple, serial, surgical procedures are necessary. Smaller congenital heart
defects can now be repaired in a cardiac catheterization lab instead of an operating room. Catheterization
procedures include balloon atrial septostomy and
balloon valvuloplasty. Surgical procedures include
arterial switch, Damus-Kaye-Stansel procedure,
Fontan procedure, Ross procedure, shunt procedure,
and venous switch or intra-atrial baffle.
Catheterization procedures
Balloon atrial septostomy and balloon valvuloplasty are cardiac catheterization procedures.
Cardiac catheterization procedures can save the lives
of critically ill neonates and in some cases eliminate
or delay more invasive surgical procedures. It is
expected that catheterization procedures will continue
to replace more types of surgery for congenital heart
defects in the future. A thin tube called a catheter is
inserted into an artery or vein in the leg, groin, or arm
and threaded into the area of the heart which needs
repair. The patient receives a local anesthetic at the
insertion site and is awake but sedated during the
procedure.
BALLOON ATRIAL SEPTOSTOMY. Balloon atrial
septostomy is the standard procedure for correcting
transposition of the great arteries; it is sometimes
used in patients with mitral, pulmonary, or tricupsid
atresia (atresia is a defect that causes the blood to
carry too little oxygen to the body). Balloon atrial
septostomy enlarges the atrial opening. A special
balloon-tipped catheter is inserted into the right
atrium and inflated to create a large opening in the
atrial septum.
BALLOON VALVULOPLASTY. Balloon valvuloplasty
uses a balloon-tipped catheter to open a narrowed
heart valve, improving the flow of blood. It is the
procedure of choice in pulmonary stenosis and is
sometimes used in aortic stenosis. Balloons made of
plastic polymers are placed at the end of the catheter
and inflated to relieve the obstruction in the heart
valve. Long-terms results are excellent in most cases.
The operative death rate is 2–4%.

Surgical procedures
These procedures are performed under general
anesthesia. Some require the use of a heart-lung
machine, which cools the body to reduce the need for
oxygen and takes over for the heart and lungs during
the procedure.
1713

Heart surgery for congenital defects

Heart surgery for congenital
defects

Heart surgery for congenital defects

ARTERIAL SWITCH. Arterial switch is performed to
correct transposition of the great arteries, where the
position of the pulmonary artery and the aorta are
reversed. The procedure involves connecting the
aorta to the left ventricle and the pulmonary artery
to the right ventricle.
DAMUS-KAYE-STANSEL PROCEDURE. Transposition
of the great arteries can also be corrected by the
Damus-Kaye-Stansel procedure, in which the pulmonary artery is cut in two and connected to the
ascending aorta and right ventricle.
FONTAN PROCEDURE. For tricuspid atresia and
pulmonary atresia, the Fontan procedure connects
the right atrium to the pulmonary artery directly or
with a conduit, and the atrial defect is closed. Survival
is over 90%.
PULMONARY ARTERY BANDING. Pulmonary artery
banding is narrowing the pulmonary artery with a
band to reduce blood flow and pressure in the lungs.
It is used for ventricular septal defect, atrioventricular
canal defect, and tricuspid atresia. Later, the band can
be removed and the defect corrected with open heart
surgery.
ROSS PROCEDURE. To correct aortic stenosis, the
Ross procedure grafts the pulmonary artery to the
aorta.
SHUNT PROCEDURE. For Tetralogy of Fallot, tricuspid atresia, or pulmonary atresia, the shunt procedure creates a passage between blood vessels, sending
blood into parts of the body that need it.
VENOUS SWITCH. For transposition of the great
arteries, venous switch creates a tunnel inside the atria
to re-direct oxygen-rich blood to the right ventricle
and aorta and venous blood to the left ventricle and
pulmonary artery.
OTHER TYPES OF SURGERY. These surgical procedures are also used to treat common congenital
heart defects. A medium to large ventricular or
atrial septal defect can be closed by suturing it or
covering it with a Dacron patch. For patent ductus
arteriosus, surgery consists of dividing the ductus
into two and tying off the ends. If performed within
the patient’s first few years, there is practically no
risk associated with this operation. Surgery for
coarctation of the aorta involves opening the chest
wall, removing the defect, and reconnecting the ends
of the aorta. If the defect is too long to be reconnected, a Dacron graft is used to replace the missing
piece. In uncomplicated cases, the risk of the operation is 1–2%.

1714

Preparation
Before surgery for congenital heart defects, the
patient will receive a complete evaluation, which
includes a physical exam, a detailed family history, a
chest x ray, an electrocardiogram, an echocardiogram,
and usually cardiac catheterization. For six to eight
hours before the surgery, the patient cannot eat or
drink anything. An electrocardiogram shows the
heart’s activity and may reveal a lack of oxygen.
Electrodes covered with conducting jelly are placed
on the patient’s chest, arms, and legs and the heart’s
impulses are traced on paper. An echocardiogram
uses sound waves to create an image of the heart’s
chambers and valves. Gel is applied to a hand-held
transducer and then pressed against the patient’s
chest. Cardiac catheterization is an invasive diagnostic
technique used to evaluate the heart in which a long
tube is inserted into a blood vessel and guided into
the heart. A contrast solution is injected to make the
heart visible on x rays.

Aftercare
After heart surgery for congenital defects, the
patient goes to an intensive care ward where he or
she is connected to a variety of tubes and monitors,
including a ventilator. Patients are monitored every
15 minutes until vital signs are stable. Heart sounds,
oxygenation, and the electrocardiogram are monitored. Chest tubes will be checked to ensure that
they’re draining properly and there is no hemorrhage.
Pain medications will be administered. Complications
such as stroke, lung blood clots, and reduced blood
flow to the kidneys will be watched for. After the
ventilator and breathing tube are removed, chest
physical therapy and exercises to improve circulation
will be started.

Risks
Complications from heart surgery for congenital defects can be severe. They include shock, congestive heart failure, lack of oxygen or too much
carbon dioxide in the blood, irregular heartbeat,
stroke, infection, kidney damage, lung blood clot,
low blood pressure, hemorrhage, cardiac arrest, and
death.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

GALE ENCYCLOPEDIA OF MEDICINE

Heart transplantation

Atresia—A congenital defect in which the blood
pumped through the body has too little oxygen. In
tricuspid atresia, the baby lacks a triscupid valve. In
pulmonary atresia, a pulmonary valve is missing.
Coarctation of the aorta—A congenital defect in
which severe narrowing or constriction of the aorta
obstructs the flow of blood.
Congenital heart defects—Congenital means conditions which are present at birth. Congenital heart
disease includes a variety of defects that babies are
born with.
Patent ductus arteriosus—A congenital defect in
which the temporary blood vessel connecting the
left pulmonary artery to the aorta in the fetus
doesn’t close in the newborn.
Septal defects—These are holes in the septum, the
muscle wall separating the right and left sides of the
heart. Atrial septal defects are openings between
the two upper heart chambers and ventricular septal defects are openings between the two lower
heart chambers.
Stenosis—A narrowing of the heart’s valves. This
congenital defect can occur in the pulmonary
(lung) or aortic (the main heart artery) valve.
Tetralogy of Fallot—A cyanotic defect in which
the blood pumped through the body has too little
oxygen. Tetralogy of Fallot includes four defects: a
large hole between the ventricles, narrowing at or
beneath the pulmonary valve, an overly muscular
right ventricle, and an aorta over the large hole.
Transposition of the great arteries—A cyanotic
defect in which the blood pumped through the
body has too little oxygen. The pulmonary artery
and the aorta are reversed.

Children’s Health Information Network. 1561 Clark Drive,
Yardley, PA 19067. (215) 493-3068. <http://
www.tchin.org>.
Congenital Heart Anomalies Support, Education &
Resources, Inc. 2112 North Wilkins Road, Swanton,
OH 43558. (419) 825-5575. <http://www.csun.edu/
hfmth006/chaser>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Heart transplantation, also called cardiac transplantation, is the replacement of a patient’s diseased or
injured heart with a healthy donor heart.

Purpose
Heart transplantation is performed on patients
with end-stage heart failure or some other lifethreatening heart disease. Before a doctor recommends heart transplantation for a patient, all other
possible treatments for his or her disease must have
been tried. The purpose of heart transplantation is to
extend and improve the life of a person who would
otherwise die from heart failure. Most patients who
receive a new heart were so sick before transplantation
that they could not live a normal life. Replacing a
patient’s diseased heart with a healthy, functioning
donor heart often allows the recipient to return to
normal daily activities.

Precautions
Because healthy donor hearts are in short supply,
strict rules dictate who should or should not get a heart
transplant. Patients who have conditions that might
cause the new heart to fail should not have a heart
transplant. Similarly, patients who may be too sick to
survive the surgery or the side effects of the drugs they
must take to keep their new heart working would not
be good transplant candidates.
Patients who have any of the following conditions
may not be eligible for heart transplantation:


active infection



pulmonary hypertension



chronic lung disease with loss of more than 40% of
lung function



untreatable liver or kidney disease



diabetes that has caused serious damage to vital
organs



disease of the blood vessels in the brain, such as a
stroke



serious disease of the arteries



mental illness or any condition that would make a
patient unable to take the necessary medicines on
schedule



continuing alcohol or drug abuse
1715

Heart transplantation

KEY TERMS

Heart transplantation

Description
National Transplant Waiting List By Organ Type (June 2000)

Patients with end-stage heart disease that threatens their life even after medical treatment may be
considered for heart transplantation. Potential candidates must have a complete medical examination
before they can be put on the transplant waiting list.
Many types of tests are done, including blood tests,
x rays, and tests of heart, lung, and other organ function. The results of these tests indicate to doctors how
serious the heart disease is and whether or not a
patient is healthy enough to survive the transplant
surgery.
Organ waiting list
A person approved for heart transplantation is
placed on the heart transplant waiting list of a heart
transplant center. All patients on a waiting list are
registered with the United Network for Organ
Sharing (UNOS). UNOS has organ transplant specialists who run a national computer network that connects all the transplant centers and organ-donation
organizations.
When a donor heart becomes available, information about it is entered into the UNOS computer and
compared to information from patients on the waiting
list. The computer program produces a list of patients
ranked according to blood type, size of the heart, and
how urgently they need a heart. Because the heart
must be transplanted as quickly as possible, the list
of local patients is checked first for a good match.
After that, a regional list, and then a national list, are
checked. The patient’s transplant team of heart and
transplant specialists makes the final decision as to
whether a donor heart is suitable for the patient.
The transplant procedure
When a heart becomes available and is approved
for a patient, it is packed in a sterile cold solution and
rushed to the hospital where the recipient is waiting.
Heart transplant surgery involves the following
basic steps:


A specialist in cardiovascular anesthesia gives the
patient general anesthesia.



Intravenous antibiotics are usually given to prevent
bacterial wound infections.



The patient is put on a heart/lung machine, which
performs the functions of the heart and lungs and
pumps the blood to the rest of the body during
surgery. This procedure is called cardiopulmonary
bypass.

1716

Organ Needed

Number Waiting

Kidney
Liver
Heart
Lung
Kidney-Pancreas
Pancreas
Heart-Lung
Intestine

48,349
15,987
4,139
3,695
2,437
942
212
137



After adequate blood circulation is established, the
patient’s diseased heart is removed.



The donor heart is attached to the patient’s blood
vessels.



After the blood vessels are connected, the new heart
is warmed up and begins beating. If the heart does
not begin to beat immediately, the surgeon may start
it with an electrical shock.



The patient is taken off the heart/lung machine.



The new heart is stimulated to maintain a regular beat
with medications for two to five days after surgery,
until the new heart functions normally on its own.

Heart transplant recipients are given immunosuppressive drugs to prevent the body from rejecting
the new heart. These drugs are usually started
before or during the heart transplant surgery.
Immunosuppressive drugs keep the body’s immune
system from recognizing and attacking the new heart
as foreign tissue. Normally, immune system cells
recognize and attack foreign or abnormal cells, such
as bacteria, cancer cells, and cells from a transplanted
organ. The drugs suppress the immune cells and allow
the new heart to function properly. However, they
can also allow infections and other adverse effects
to occur to the patient.
Because the chance of rejection is highest during
the first few months after the transplantation, recipients are usually given a combination of three or four
immunosuppressive drugs in high doses during this
time. Afterwards, they must take maintenance doses
of immunosuppressive drugs for the rest of their lives.
Cost and insurance coverage
The total cost for heart transplantation varies,
depending on where it is performed, whether transportation and lodging are needed, and on whether there
are any complications. The costs for the surgery and
GALE ENCYCLOPEDIA OF MEDICINE

Heart transplantation
A comparison of the old and new hearts of Dylan Stork, the smallest heart transplant recipient in the world. Dylan was seven
weeks old and weighed 5.5 pounds (2.5 kg) at the time of the operation. (Photograph by Alexander Tsiaras, Photo Researchers, Inc.
Reproduced by permission.)

first year of care are estimated to be about $250,000.
The medical tests and medications after the first year
cost about $21,000 per year.
Insurance coverage for heart transplantation
varies depending on the policy. Most commercial
insurance companies pay a certain percentage of heart
transplant costs. Medicare pays for heart transplants
if the surgery is performed at Medicare-approved
centers. Medicaid pays for heart transplants in
33 states and in the District of Colombia.

Preparation
Before patients are put on the transplant waiting
list, their blood type is determined so a compatible
donor heart can be found. The heart must come from
a person with the same blood type as the patient,
unless it is blood type O. A blood type O heart can
be transplanted into a person with any type of blood.
A panel reactive antibodies (PRA) test is also done
before heart transplantation. This test tells doctors
whether or not the patient is at high risk for having a
GALE ENCYCLOPEDIA OF MEDICINE

hyperacute reaction against a donor heart. A hyperacute reaction is a strong immune response against the
new heart that happens within minutes to hours after
the new heart is transplanted. If the PRA shows that a
patient has a high risk for this kind of reaction, then a
crossmatch is done between a patient and a donor heart
before transplant surgery. A crossmatch checks how
close the match is between the patient’s tissue type
and the tissue type of the donor heart.
Most people are not high risk and a crossmatch
usually is not done before the transplant because the
surgery must be done as quickly as possible after a
donor heart is found.
While waiting for heart transplantation, patients
are given treatment to keep the heart as healthy as
possible. They are regularly checked to make sure the
heart is pumping enough blood. Intravenous medications may be used to improve cardiac output. If these
drugs are not effective, a mechanical pump can help
keep the heart functioning until a donor heart becomes
available. Inserted through an artery into the aorta, the
pump assists the heart in pumping blood.
1717

Heart transplantation

Aftercare
Immediately following surgery, patients are monitored closely in the intensive care unit (ICU) of the
hospital for 24–72 hours. Most patients need to receive
oxygen for four to 24 hours following surgery. Blood
pressure, heart function, and other organ functions
are carefully monitored during this time.
Heart transplant patients start taking immunosuppressive drugs before or during surgery to prevent
immune rejection of the heart. High doses of immunosuppressive drugs are given at this time, because
rejection is most likely to happen within the first
few months after the surgery. A few months after
surgery, lower doses of immunosuppressive drugs
usually are given and must be taken for the rest of
the patient’s life.
For six to eight weeks after the transplant surgery,
patients usually come back to the transplant center
twice a week for physical examinations and medical
tests. These tests check for any signs of infection,
rejection of the new heart, or other complications.
In addition to physical examination, the following
tests may be done during these visits:


laboratory tests to check for infection



chest x ray to check for early signs of lung infection



electrocardiogram (ECG) to check heart function



echocardiogram to check the function of the ventricles
in the heart



blood tests to check liver and kidney function



complete blood counts (CBC) to check the numbers
of blood cells



taking of a small tissue sample from the donor heart
(endomyocardial biopsy) to check for signs of
rejection.

During the physical examination, the blood pressure is checked and the heart sounds are listened to
with a stethoscope to determine if the heart is beating
properly and pumping enough blood. Kidney and
liver function are checked because these organs may
lose function if the heart is being rejected.
An endomyocardial biopsy is the removal of a
small sample of the heart muscle. This is done with a
very small instrument that is inserted through an
artery or vein and into the heart. The heart muscle
tissue is examined under a microscope for signs that
the heart is being rejected. Endomyocardial biopsy is
usually done weekly for the first four to eight weeks
after transplant surgery and then at longer intervals
after that.
1718

Risks
The most common and dangerous complications
of heart transplant surgery are organ rejection and
infection. Immunosuppressive drugs are given to
prevent rejection of the heart. Most heart transplant
patients have a rejection episode soon after transplantation, but doctors usually diagnose it immediately
when it will respond readily to treatment. Rejection
is treated with combinations of immunosuppressive
drugs given in higher doses than maintenance immunosuppression. Most of these rejection situations are
successfully treated.
Infection can result from the surgery, but most
infections are a side effect of the immunosuppressive
drugs. Immunosuppressive drugs keep the immune
system from attacking the foreign cells of the donor
heart. However, the suppressed immune cells are also
unable to adequately fight bacteria, viruses, and other
microorganisms. Microorganisms that normally do
not affect persons with healthy immune systems can
cause dangerous infections in transplant patients
taking immunosuppressive drugs.
Patients are given antibiotics during surgery to
prevent bacterial infection. Patients may also be
given an antiviral drug to prevent virus infections.
Patients who develop infections may need to have
their immunosuppressive drugs changed or the dose
adjusted. Infections are treated with antibiotics or
other drugs, depending on the type of infection.
Other complications that can happen immediately
after surgery are:


bleeding



pressure on the heart caused by fluid in the space
surrounding the heart (pericardial tamponade)



irregular heart beats



reduced cardiac output



increased amount of blood in the circulatory system



decreased amount of blood in the circulatory system

About half of all heart transplant patients
develop coronary artery disease 1–5 years after the
transplant. The coronary arteries supply blood to
the heart. Patients with this problem develop chest
pains called angina. Other names for this complication are coronary allograft vascular disease and
chronic rejection.

Outcomes
Heart transplantation is an appropriate treatment
for many patients with end-stage heart failure.
GALE ENCYCLOPEDIA OF MEDICINE

Anesthesia—Loss of the ability to feel pain, caused
by administration of an anesthetic drug.
Angina—Characteristic chest pain which occurs
during exercise or stress in certain kinds of heart
disease.
Cardiopulmonary bypass—Mechanically circulating the blood with a heart/lung machine that
bypasses the heart and lungs.

After transplant, most patients regain normal
heart function, meaning the heart pumps a normal
amount of blood. A transplanted heart usually beats
slightly faster than normal because the heart nerves
are cut during surgery. The new heart also does not
increase its rate as quickly during exercise. Even so,
most patients feel much better and their capacity for
exercise is dramatically improved from before they
received the new heart. About 85% of patients return
to work and other daily activities. Many are able to
participate in sports.

Cardiovascular—Having to do with the heart and
blood vessels.

Resources

Complete blood count (CBC)—A blood test to
check the numbers of red blood cells, white blood
cells, and platelets in the blood.

American Council on Transplantation. P.O. Box 1709,
Alexandria, VA 22313. 1-800-ACT-GIVE.
Health Services and Resources Administration, Division of
Organ Transplantation. Room 11A-22, 5600 Fishers
Lane, Rockville, MD 20857.
United Network for Organ Sharing (UNOS). 1100 Boulders
Parkway, Suite 500, P.O. Box 13770, Richmond, VA
23225-8770. (804) 330-8500. <http://www.unos.org>.

Coronary artery disease—Blockage of the arteries
leading to the heart.
Crossmatch—A test to determine if patient and
donor tissues are compatible.
Donor—A person who donates an organ for
transplantation.
Echocardiogram—A test that visualizes and
records the position and motion of the walls of the
heart using ultrasound waves.
Electrocardiogram (ECG)—A test that measures
electrical conduction of the heart.
End-stage heart failure—Severe heart disease that
does not respond adequately to medical or surgical
treatment.
Endomyocardial biopsy—Removal of a small sample of heart tissue to check it for signs of damage
caused by organ rejection.
Fatigue—Loss of energy; tiredness.
Graft—A transplanted organ or other tissue.
Immunosuppressive drug—Medication used to
suppress the immune system.
Inotropic drugs—Medications used to stimulate
the heart beat.
Pulmonary hypertension—An increase in the pressure in the blood vessels of the lungs.
Recipient—A person who receives an organ
transplant.

The outcomes of heart transplantation depend on the
patient’s age, health, and other factors. About 73% of
heart transplant patients are alive four years after
surgery.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

OTHER

‘‘What Every Patient Needs to Know.’’ United Network
forOrgan Sharing (UNOS). <http://www.unos.org/
frame_Default.asp?Category=Patients>.

Toni Rizzo

Heart tumors see Myxoma

Heart valve repair
Definition
Heart valve repair is a surgical procedure used to
correct a malfunctioning heart valve. Repair usually
involves separating the valve leaflets (the one-way
‘‘doors’’ of the heart valve which open and close to
pump blood through the heart) or forcing them open
with a balloon catheter, a technique known as balloon
valvuloplasty.

Purpose
To correct damage to the mitral, aortic, pulmonary, or tricuspid heart valves caused by a systemic
infection, endocarditis, rheumatic heart disease, a
congenital heart defect, or mitral and/or aortic valve
disease. Damaged valves may not open properly
(stenosis) or they may not close adequately (valve
regurgitation, insufficiency, or incompetence).
1719

Heart valve repair

KEY TERMS

Heart valve repair

Precautions
Patients who have a diseased heart valve that is
badly scarred or calcified may be better candidates for
valve replacement surgery.

Description
Heart valve repair is performed in a hospital
setting by a cardiac surgeon. During valve repair
surgery, the patient’s heart is stopped, and his/her
blood is circulated outside of the body through an
extracorporeal bypass circuit, also called heart-lung
machine or just ‘‘the pump.’’ The extracorporeal
circuit consists of tubing and medical devices that
take over the function of the patient’s heart and
lungs during the procedure. As blood passes through
the circuit, carbon dioxide is removed from the bloodstream and replaced with oxygen. The oxygenated
blood is then returned to the body. Other components
may also be added to the circuit to filter fluids from
the blood or concentrate red blood cells.
In cases of valve disease where the leaflets have
become fused together, a procedure known as a valvulotomy is performed. In valvulotomy, the leaflets of the
valves are surgically separated, or partially resected,
with an incision to increase the size of the valve opening.
The surgeon may also make adjustments to the chordae, the cord-like tissue that connects the valve leaflets
to the ventricle muscles, to improve valve function.
Another valve repair technique, balloon valvuloplasty, is used in patients with pulmonary, aortic, and
mitral valve stenosis to force open the valve.
Valvuloplasty is similar to a cardiac angioplasty procedure in that it involves the placement of a balloontipped catheter into the heart. Once inserted into the
valve, the balloon is inflated and the valve dilates, or
opens. Valvuloplasty does not require a bypass circuit.

Preparation
A number of diagnostic tests may be administered
prior to valve repair surgery. Magnetic resonance
imaging (MRI), echocardiogram, angiogram, and/or
scintigram are used to help the surgeon get an accurate
picture of the extent of damage to the heart valve and
the status of the coronary arteries.

Aftercare
The patient’s blood pressure and vital signs will
be carefully monitored following a valve repair procedure, and he or she watched closely for signs of edema
or congestive heart failure.
1720

KEY TERMS
Angiogram—An angiogram uses a radiopaque substance, or dye, to make the blood vessels or arteries
visible under x ray.
Calcified—Hardened by calcium deposits.
Catheter—A long, thin, flexible tube used in valvuloplasty to widen the valve opening.
Echocardiogram—Ultrasound of the heart; generates a picture of the heart through the use of
soundwaves.
Edema—Fluid accumulation in the body.
Scintigram—A nuclear angiogram; a scintigram
involves injection of a radioactive substance into
the patient’s circulatory system. As the substance
travels through the body, a special scanning camera
takes pictures.
Stenosis—Narrowing of the heart valve opening.

Echocardiography or other diagnostic tests are
ordered for the patient at some point during or after
surgery to evaluate valvular function. A cardiac rehabilitation program may also be recommended to assist
the patient in improving exercise tolerance after the
procedure.

Risks
As with any invasive surgical procedure, hemorrhage, infarction, stroke, heart attack, and infection
are all possible complications of heart valve repair.
The overall risks involved with the surgery depend
largely on the complexity of the procedure and physical condition of the patient.

Normal results
Ideally, a successful heart valve repair procedure
will return heart function to age-appropriate levels. If
valvuloplasty is performed, a follow-up valve repair or
replacement surgery may be necessary at a later date.
Resources
BOOKS

DeBakey, Michael E., and Antonio Gotto, Jr. The New
Living Heart. Holbrook, MA: Adams Media
Corporation, 1997.

Paula Anne Ford-Martin
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Heart valve replacement is a surgical procedure
during which surgeons remove a damaged valve from
the heart and substitute a healthy one.

Purpose
Four valves direct blood to and from the body
through the heart: the aortic valve, the pulmonic
valve, the tricuspid valve, and the mitral valve. Any
of these valves may malfunction because of a birth
defect, infection, disease, or trauma. When the malfunction is so severe that it interferes with blood flow,
an individual will have heart palpitations, fainting
spells, and/or difficulty breathing. These symptoms
will progressively worsen and cause death unless the
damaged valve is replaced surgically.

Donor or pulmonic valves are given only to those
patients who will deteriorate rapidly because of a
narrowing of the passageway between the aorta and
the left ventrical (aortic stenosis). These valves are
limited in their use because of the small supply available from donors and the strain that could be caused
by removing and transferring a patient’s own pulmonic valve.

Preparation
Precautions
Abnormal tricuspid valves usually are not replaced
because they do not cause serious symptoms. Mildly or
even moderately diseased mitral valves may not need
to be replaced because their symptoms are tolerable
or they can be treated with such drugs as beta blockers
or calcium antagonists, which slow the heart rate.
However, a severely diseased mitral valve should be
repaired or replaced unless the person is too ill to tolerate
the operation because of another condition or illness.

Description
After cutting through and separating the breastbone and ribs, surgeons place the patient on a cardiopulmonary bypass machine, which will perform the
functions of the heart and lungs during the operation.
They then open the heart and locate the faulty valve.
Slicing around the edges of the valve, they loosen it
from the tendons that connect it to the rest of the heart
and withdraw it. The new valve is inserted and sutured
into place. The patient is then taken off the bypass
machine and the chest is closed. The surgery takes
three to five hours and is covered by most insurance
plans.
There are three types of replacement valves. One
class is made from animal tissue, usually a pig’s aortic
valve. Another is mechanical and is made of metal and
plastic. The third, includes human valves that have
been removed from an organ donor or that, rarely,
are the patient’s own pulmonic valve.
GALE ENCYCLOPEDIA OF MEDICINE

Before patients undergo heart valve replacement,
they must be evaluated carefully for any signs that they
may not tolerate the surgery.
Preoperative tests include:


electrocardiography, which assesses the electrical
activity of the heart



echocardiography, which uses sound waves to show
the extent of the obstruction of blood flow through
the heart and determine the degree of loss of heart
function due to the malfunctioning valve



chest x ray, which provides an overall view of the
anatomy of the heart and the lungs

Cardiac catheterization may also be performed to
further asses the valve and to determine if coronary
bypass surgery should also be done.

Aftercare
A patient usually spends one to three days in the
hospital intensive care unit (ICU) after heart valve
replacement so that the working of his or her heart
and circulation can be monitored closely. When first
brought to the ICU after surgery, the patient undergoes a neurological examination to be sure he or she
has not suffered a stroke. The patient continues to
breathe by means of a tube inserted in the trachea at
the time of surgery. This mechanical ventilation is not
withdrawn until the patient is fully awake from
anesthesia, shows signs that he or she can breathe
1721

Heart valve replacement

Heart valve replacement

There is no single ideal replacement valve. The
choice between an animal valve or a mechanical
valve depends largely on the age of the patient.
Because valves obtained from animals have a life
expectancy of 7–15 years, they usually are given to
older patients. Mechanical valves are used in younger
patients because they are more durable. Because
mechanical valves are made of foreign material, however, blood clots can form on their surface. Therefore,
patients who receive these valves must take anticoagulants the rest of their lives.

Heart valve replacement

KEY TERMS

Open heart surgery showing replacement of a valve.
(Photograph by David Leah. Photo Researchers. Reproduced by
permission.)

satisfactorily without mechanical support, and has
steadfast circulation.
Once stablilized, the patient is transferred to a
standard medical/surgical unit where he or she receives
drugs that will prevent excess fluid from building up
around the heart. As soon as possible, the patient
begins walking and exercising to regain strength. He
or she is also placed on a diet that is low in salt and
cholesterol.
After being released from the hospital, the patient
continues a daily exercise program that includes
vigorous walking, and he or she may also join a recommended cardiac rehabilitation program. He or she
usually can return to work or other normal activities
within two months of the surgery.

Risks
Complications following heart valve replacement
are not common, but can be serious. All valves made
from animal tissue will develop calcium deposits over
time. If these deposits hamper the function of the
valve, it must be replaced. Valves may become dislodged. Blood clots may form on the surface of the
substitute valve, break off into the general circulation,
and become wedged in an artery supplying blood to
the brain, kidneys, or legs. These blood clots may
cause fainting spells, stroke, kidney failure, or loss of
circulation to the legs. These blood clots can be treated
with drugs or surgery.
Infection of heart muscle affects up to 2% of
patients who have heart valve replacement. Such
an infection is treated with intravenous antibiotics. If
the infection persists, the new valve may have to be
replaced.
1722

Anticoagulants—Drugs that prevent blood clots
from forming.
Aortic valve—A fold in the channel leading from
the aorta to the left ventricle of the heart. The aortic
valve directs blood flow that has received oxygen
from the lungs to the aorta which transmits blood to
the rest of the body.
Cardiac catheterization—A thin tube called a
catheter is inserted into an artery or vein in the leg,
groin or arm. The catheter tube is carefully threaded
into the area of the heart needing surgical repair.
A local anaesthesia is used at the insertion sites.
Cardiopulmonary bypass machine—A mechanical
instrument that takes over the circulation of the
body while heart surgery is taking place.
Echocardiography—A diagnostic instrument that
assesses the structure of the heart using sound
waves.
Electrocardiography—A diagnostic instrument
that evaluates the function of the heart by measuring the electrical activity generated by the beating
of the heart.
Mitral valve—A fold in between the left atrium and
the left ventricle of the heart that directs blood that
has received oxygen from the lungs to the aortic
valve and the aorta.
Pulmonic valve—A fold in the pulmonary artery
that directs blood to the lungs. It may be transferred
to replace a severely diseased aortic valve during
heart valve replacement surgery for aortic stenosis.
Tricuspid valve—A fold in between the right atrium
and the right ventricle of the heart that directs blood
that needs oxygen to the lungs.

Normal results
Few patients die as a result of the surgery.
Approximately 3% of all patients die during or immediately after heart valve replacement, and less than 1%
of patients below the age of 65 die because of the
operation. The vast majority of patients who have
heart valve replacement return to normal activity
after the surgery. Depending on the type of valve they
receive, these patients will have no symptoms of valve
abnormality for at least seven years. Also, their quality
of life will improve because they may no longer have
difficulty breathing, fainting spells, or palpitations.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

American Heart Association. American HeartAssociation’s
Your Heart: An Owner’s Manual. Englewood Cliffs, NJ:
Prentice Hall, 1991.
ORGANIZATIONS

The American College of Cardiology. 9111 Old Georgetown
Road, Bethesda, MD 20814. (800) 253-4636. <http://
www.acc.org>.
American College of Surgeons. 55 E. Erie St., Chicago, IL
60611. (312) 202-5000. <http://www.facs.org>.
American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Karen Marie Sandrick

Heartburn

The stomach has a thick mucous coating that
protects it from the strong acid it secretes into its
interior when food is present, but the much thinner
esophageal coating doesn’t provide protection against
acid. Thus, if the LES opens inappropriately or fails to
close completely, and stomach contents leak into the
esophagus, the esophagus can be burned by acid. The
resulting burning sensation is called heartburn.
Occasional heartburn has no serious long-lasting
effects, but repeated episodes of gastroesophageal
reflux can ultimately lead to esophageal inflammation
(esophagitis) and other damage. If episodes occur
more frequently than twice a week, and the esophagus
is repeatedly subjected to acid and digestive enzymes
from the stomach, ulcerations, scarring, and thickening of the esophagus walls can result. This thickening
of the esophagus wall causes a narrowing of the interior of the esophagus. Such narrowing affects swallowing and peristaltic movements. Repeated irritation can
also result in changes in the types of cells that line the
esophagus. The condition associated with these
changes is termed Barrett’s syndrome and can lead to
esophageal cancer.

Definition
Heartburn is a burning sensation in the chest that
can extend to the neck, throat, and face; it is worsened
by bending or lying down. It is the primary symptom
of gastroesophageal reflux, which is the movement of
stomach acid into the esophagus. On rare occasions, it
is due to gastritis (stomach lining inflammation).

Causes and symptoms
Causes
A number of different factors may contribute to
LES malfunction with its consequent gastroesophageal acid reflux:


The eating of large meals that distend the stomach
can cause the LES to open inappropriately.



Lying down within two to three hours of eating can
cause the LES to open.



Obesity, pregnancy, and tight clothing can impair the
ability of the LES to stay closed by putting pressure
on the abdomen.



Certain drugs, notably nicotine, alcohol, diazepam
(Valium), meperidine (Demerol), theophylline, morphine, prostaglandins, calcium channel blockers,
nitrate heart medications, anticholinergic and adrenergic drugs (drugs that limit nerve reactions),
including dopamine, can relax the LES.



Progesterone is thought to relax the LES.



Greasy foods and some other foods such as chocolate, coffee, and peppermint can relax the LES.



Paralysis and scleroderma can cause the LES to
malfunction.



Hiatus hernia may also cause heartburn according to
some gastroenterologists. (Hiatus hernia is a

Description
More than one-third of the population is afflicted
by heartburn, with about one-tenth afflicted daily.
Infrequent heartburn is usually without serious consequences, but chronic or frequent heartburn (recurring
more than twice per week) can have severe consequences. Accordingly, early management is important.
Understanding heartburn depends on understanding the structure and action of the esophagus.
The esophagus is a tube connecting the throat to the
stomach. It is about 10 in (25 cm) long in adults, lined
with squamous (plate-like) epithelial cells, coated with
mucus, and surrounded by muscles that push food
to the stomach by sequential waves of contraction
(peristalsis). The lower esophageal sphincter (LES) is
a thick band of muscles that encircles the esophagus
just above the uppermost part of the stomach. This
sphincter is usually tightly closed and normally opens
only when food passes from the esophagus into the
stomach. Thus, the contents of the stomach are
normally kept from moving back into the esophagus.
GALE ENCYCLOPEDIA OF MEDICINE

1723

Heartburn

Resources

Heartburn

protrusion of part of the stomach through the
diaphragm to a position next to the esophagus.)
Symptoms
Heartburn itself is a symptom. Other symptoms
also caused by gastroesophageal reflux can be associated with heartburn. Often heartburn sufferers
salivate excessively or regurgitate stomach contents
into their mouths, leaving a sour or bitter taste.
Frequent gastroesophageal reflux leads to additional
complications including difficult or painful swallowing,
sore throat, hoarseness, coughing, laryngitis, wheezing,
asthma, pneumonia, gingivitis, bad breath, and earache.

Diagnosis
Gastroenterologists and internists are best
equipped to diagnose and treat gastroesophageal
reflux. Diagnosis is usually based solely on patient
histories that report heartburn and other related
symptoms. Additional diagnostic procedures can confirm the diagnosis and assess damage to the esophagus, as well as monitor healing progress. The following
diagnostic procedures are appropriate for anyone who
has frequent, chronic, or difficult-to-treat heartburn
or any of the complicating symptoms noted in the
previous paragraph.
X rays taken after a patient swallows a barium
suspension can reveal esophageal narrowing, ulcerations or a reflux episode as it occurs. However, this
procedure cannot detect the structural changes
associated with different degrees of esophagitis. This
diagnostic procedure has traditionally been called the
‘‘upper GI series’’ or ‘‘barium swallow’’ and costs
about $250.00.
Esophagoscopy is a newer procedure that uses a
thin flexible tube to view the inside of the esophagus
directly. It should be done by a gastroenterologist
or gastrointestinal endoscopist and costs about $700.
It gives an accurate picture of any damage present and
gives the physician the ability to distinguish between
different degrees of esophagitis.
Other tests may also be used. They include pressure
measurements of the LES; measurements of esophageal
acidity (pH), usually throughout a 24-hour period; and
microscopic examination of biopsied tissue from the
esophageal wall (to inspect esophageal cell structure
for Barrett’s syndrome and malignancies).
New technology introduced by 2003 allows for
continuous monitoring of pH levels to help determine
the cause. A tiny wireless capsule can be delivered to
the lining of the esophagus through a catheter and
1724

data recorder on a device the size of a pager that is
clipped to the patient’s belt or purse for 48 hours. The
capsule eventually sloughs off and passes harmlessly
through the gastrointestinal tract in seven to 10 days.
Note: A burning sensation in the chest is usually
heartburn and is not associated with the heart.
However, chest pain that radiates into the arms and
is not accompanied by regurgitation is a warning of a
possible serious heart problem. Anyone with these
symptoms should contact a doctor immediately.

Treatment
Drugs
Occasional heartburn is probably best treated
with over-the-counter antacids. These products go
straight to the esophagus and immediately begin to
decrease acidity. However, they should not be used as
the sole treatment for heartburn sufferers who either
have two or more episodes per week or who suffer
for periods of more than three weeks. There is a risk
of kidney damage and other metabolic changes.
H2 blockers (histamine receptor blockers, such as
Pepsid AC, Zantac, Tagamet) decrease stomach acid
production and are effective against heartburn. H2
blocker treatment also allows healing of esophageal
damage but is not very effective when there is a high
degree of damage. It takes 30–45 minutes for these
drugs to take effect, so they must be taken prior to
an episode. Thus, they should be taken daily, usually
two to four times per day for several weeks. Six to
12 weeks of standard-dose treatment relieves symptoms in about one-half the patients. Higher doses
relieve symptoms in a greater fraction of the population, but at least 25% of heartburn sufferers are not
helped by H2 blockers.
Proton-pump inhibitors also inhibit acid production by the stomach, but are much more effective than
H2 blockers for some people. They are also more
effective in aiding the healing process. Esophagitis is
healed in about 90% of the patients undergoing proton-pump inhibitor treatment.
The long-term effects of inhibiting stomach acid
production are unknown. Without the antiseptic
effects of a consistently very acidic stomach environment, users of H2 blockers or proton-pump inhibitors
may become more susceptible to bacterial and viral
infection. Absorption of some drugs is also lowered by
this less-acidic environment.
Prokinetic agents (also known as motility drugs)
act on the LES, stimulating it to close more tightly,
thereby keeping stomach contents out of the
GALE ENCYCLOPEDIA OF MEDICINE

Herbal remedies include bananas, aloe vera gel,
chamomile (Matricaria recutita), ginger (Zingiber officinale), and citrus juices, but there is little agreement
here. For example, ginger, which seems to help some
people, is claimed by other practitioners to cause
heartburn and is thought to relax the LES. There are
also many recommendations to avoid citrus juices,
which are themselves acidic. Licorice (Glycyrrhiza
uralensis) can help relieve the symptoms of heartburn
by reestablishing balance in the acid output of the
stomach.
An illustration of foaming antacid on top of the contents of a
human stomach. Heartburn is caused by a backflow of the
stomach’s acidic contents into the esophagus, causing
inflammation and a sense of pain that can rise to the throat.
(Illustration by John Bavosi, Custom Medical Stock Photo.
Reproduced by permission.)

esophagus. It is not known how effectively these drugs
promote healing. Some of the early motility drugs had
serious neurological side effects, but a newer drug,
cisapride, seems to act only on digestive system nerve
connections.

Several homeopathic remedies are useful in treating heartburn symptoms. Among those most often
recommended are Nux vomica, Carbo vegetabilis, and
Arsenicum album. Acupressure and acupuncture may
also be helpful in treating heartburn.
Sodium bicarbonate (baking soda) is an inexpensive alternative to use as an antacid. It reduces
esophageal acidity immediately, but its effect is not
long-lasting and should not be used by people on
sodium-restricted diets.

Prognosis
Surgery
Fundoplication, a surgical procedure to increase
pressure on the LES by stretching and wrapping the
upper part of the stomach around the sphincter, is a
treatment of last resort. About 10% of heartburn
sufferers undergo this procedure. It is not always effective and its effectiveness may decrease over time, especially several years after surgery. Dr. Robert Marks
and his colleagues at the University of Alabama
reported in 1997 on the long-term outcome of this
procedure. They found that 64% of the patients in
their study who had fundoplication between 1992
and 1995 still suffered from heartburn and reported
an impaired quality of life after the surgery.
However, laparoscopy (an examination of the
interior of the abdomen by means of the laparoscope)
now provides hope for better outcomes.
Fundoplication performed with a laparoscope is less
invasive. Five small incisions are required instead of
one large incision. Patients recover faster, and it is
likely that studies will show they suffer from fewer
surgical complications.

Alternative treatment
Prevention, as outlined below, is a primary feature
for heartburn management in alternative medicine
GALE ENCYCLOPEDIA OF MEDICINE

The prognosis for people who get heartburn only
occasionally or people without esophageal damage
is excellent. The prognosis for people with esophageal
damage who become involved in a treatment program
that promotes healing is also excellent. The prognosis
for anyone with esophageal cancer is very poor. There
is a strong likelihood of a painful illness and a less than
5% chance of surviving more than five years.

Prevention
Given the lack of completely satisfactory treatments for heartburn or its consequences and the lack
of a cure for esophageal cancer, prevention is of the
utmost importance. Proponents of traditional and
alternative medicine agree that people disposed to
heartburn should:


avoid eating large meals



avoid alcohol, caffeine, fatty foods, fried foods, hot
or spicy foods, chocolate, peppermint, and nicotine



avoid drugs known to contribute to heartburn, such
as nitrates (heart medications such as Isonate and
Nitrocap), calcium channel blockers (e.g., Cardizem
and Procardia), and anticholinergic drugs (e.g., Probanthine and Bentyl), and check with their doctors
about any drugs they are taking
1725

Heartburn

and traditional medicine. Dietary adjustments can
eliminate many causes of heartburn.

Heat disorders

KEY TERMS
Barrett’s syndrome—Also called Barrett’s esophagus or Barrett’s epithelia, this is a condition where
the squamous epithelial cells that normally line the
esophagus are replaced by thicker columnar
epithelial cells.
Digestive enzymes—Molecules that catalyze the
breakdown of large molecules (usually food) into
smaller molecules.
Esophagitis—Inflammation of the esophagus.
Fundoplication—A surgical procedure that
increases pressure on the LES by stretching and
wrapping the upper part of the stomach around
the sphincter.
Gastroesophageal reflux—The flow of stomach
contents into the esophagus.
Hiatus hernia—A protrusion of part of the stomach
through the diaphragm to a position next to the
esophagus.
Metabolic—Refers to the chemical reactions in
living things.
Mucus—Thick, viscous, gel-like material that functions to moisten and protect inner body surfaces.
Peristalsis—A sequence of muscle contractions
that progressively squeeze one small section of
the digestive tract and then the next to push food
along the tract, something like pushing toothpaste
out of its tube.
Scleroderma—An autoimmune disease with
many consequences, including esophageal wall
thickening.
Squamous epithelial cells—Thin, flat cells found in
layers or sheets covering surfaces such as skin and
the linings of blood vessels and esophagus.

in Great Britain in 2004 also looked at using a combination of aspirin and an anti-ulcer drug to try to
prevent Barrett’s esophagus from forming in patients
with long-term heartburn. Aspirin has been found in
previous studies to reduce cases of esophageal cancer.
However, since one of its side effects is an increased
risk of stomach ulcers, the researchers were including
an effective anti-ulcer drug for participants.
Resources
PERIODICALS

‘‘Aspirin Trial Launched to Block Heartburn’s Switch to
Cancer.’’ Drug Week January 23, 2004:188.
Bealfsky, Peter C., and William Halsey. ‘‘An Endoscopic
View of a Wireless pH–Monitoring Capsule.’’ Ear, Nose
and Throat Journal April 2003: 254.
ORGANIZATIONS

The American College of Gastroenterology (ACG). PO Box
3099, Alexandria, VA 22302. (800) HRT-BURN.
<http://www.healthtouch.com>.
The American Gastroenterological Association (AGA).
7910 Woodmont Ave., 7th Floor, Bethesda, MD 20814.
(310) 654-2055. <http://www.gastro.org/index.html>.
American Society for Gastrointestinal Endoscopy. 13 Elm
St., Manchester, MA 01944. (508) 526-8330. <http://
www.asge.org/doc/201>.
National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/
digest/nddic.htm>.

Lorraine Lica, PhD
Teresa G. Odle

Heat cramps see Heat disorders

Ulceration—An open break in surface tissue.

Heat disorders


avoid clothing that fits tightly around the abdomen



control body weight



wait about three hours after eating before going to
bed or lying down



elevate the head of the bed 6–9 inches to alleviate
heartburn at night. This can be done with bricks
under the bed or with a wedge designed for this
purpose.

Preventing heartburn’s switch to cancer begins
with preventing heartburn in the first place. A study
1726

Definition
Heat disorders are a group of physically related
illnesses caused by prolonged exposure to hot temperatures, restricted fluid intake, or failure of temperature regulation mechanisms of the body. Disorders of
heat exposure include heat cramps, heat exhaustion,
and heat stroke (also called sunstroke). Hyperthermia
is the general name given to heat-related illnesses. The
two most common forms of hyperthermia are heat
exhaustion and heat stroke, which is especially
dangerous and requires immediate medical attention.
GALE ENCYCLOPEDIA OF MEDICINE

Heat disorders are harmful to people of all
ages, but their severity is likely to increase as people age. Heat cramps in a 16-year-old may be heat
exhaustion in a 45-year-old and heat stroke in a
65-year-old. The body’s temperature regulating
mechanisms rely on the thermal regulating centers
in the brain. Through these complex centers, the
body tries to adapt to high temperatures by adjusting the amount of salt in the perspiration. Salt
helps the cells in body tissues retain water. In hot
weather, a healthy body will lose enough water to
cool the body while creating the lowest level of
chemical imbalance. Regardless of extreme weather
conditions, the healthy human body keeps a steady
temperature of approximately 98.6  F (37  C). In
hot weather, or during vigorous activity, the body
perspires. As perspiration evaporates from the
skin, the body is cooled. If the body loses too
much salt and fluids, the symptoms of dehydration
can occur.
Heat cramps
Heat cramps are the least severe of the heatrelated illnesses. This heat disorder is often the first
signal that the body is having difficulty with increased
temperature. Individuals exposed to excessive heat
should think of heat cramps as a warning sign to a
potential heat-related emergency.
Heat exhaustion
Heat exhaustion is a more serious and complex
condition than heat cramps. Heat exhaustion can
result from prolonged exposure to hot temperatures,
restricted fluid intake, or failure of temperature regulation mechanisms of the body. It often affects athletes, firefighters, construction workers, factory
workers, and anyone who wears heavy clothing in
hot humid weather.
Heat stroke
Heat exhaustion can develop rapidly into heat
stroke. Heat stroke can be life threatening and because
the percentage of victims dying from heat stroke is
very high, immediate medical attention is critical
when problems first begin. Heat stroke, like heat
exhaustion, is also a result of prolonged exposure to
hot temperatures, restricted fluid intake, or failure of
temperature regulation mechanisms of the body.
However, the severity of impact on the body is much
greater with heat stroke.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Heat cramps
Heat cramps are painful muscle spasms caused by
the excessive loss of salts (electrolytes), due to heavy
perspiration. The muscle tissue becomes less flexible,
causing pain, difficult movement, and involuntary
tightness. Heavy exertion in extreme heat, restricted
fluid intake, or failure of temperature regulation
mechanisms of the body may lead to heat cramps.
This disorder occurs more often in the legs and abdomen than in other areas of the body. Individuals at
higher risk are those working in extreme heat, elderly
people, young children, people with health problems,
and those who are unable to naturally and properly
cool their bodies. Individuals with poor circulation
and who take medications to reduce excess body fluids
can be at risk when conditions are hot and humid.
Heat exhaustion
Heat exhaustion is caused by exposure to high
heat and humidity for many hours, resulting in excessive loss of fluids and salts through heavy perspiration.
The skin may appear cool, moist, and pale. The individual may complain of headache and nausea with a
feeling of overall weakness and exhaustion. Dizziness,
faintness, and mental confusion are often present, as is
rapid and weak pulse. Breathing becomes fast and
shallow. Fluid loss reduces blood volume and lowers
blood pressure. Yellow or orange urine often is a result
of inadequate fluid intake, along with associated
intense thirst. Insufficient water and salt intake or a
deficiency in the production of sweat place an individual at high risk for heat exhaustion.
Heat stroke
Heat stroke is caused by overexposure to extreme
heat, resulting in a breakdown in the body’s heat
regulating mechanisms. The body’s temperature
reaches a dangerous level, as high as 106  F (41.1  C).
An individual with heat stroke has a body temperature
higher than 104  F (40  C). Other symptoms include
mental confusion with possible combativeness and
bizarre behavior, staggering, and faintness.
The pulse becomes strong and rapid (160–180
beats per minute) with the skin taking on a dry and
flushed appearance. There is often very little perspiration. The individual can quickly lose consciousness or
have convulsions. Before heat stroke, an individual
suffers from heat exhaustion and the associated symptoms. When the body can no longer maintain a normal
temperature, heat exhaustion becomes heat stroke.
1727

Heat disorders

Description

Heat disorders

Heat stroke is a life-threatening medical emergency
that requires immediate initiation of life-saving
measures.

Diagnosis
The diagnosis of heat cramps usually involves the
observation of individual symptoms such as muscle
cramping and thirst. Diagnosis of heat exhaustion or
heat stroke, however, may require a physician to
review the medical history, document symptoms, and
obtain a blood pressure and temperature reading. The
physician may also take blood and urine samples for
further laboratory testing. A test to measure the
body’s electrolytes can also give valuable information
about chemical imbalances caused by the heat-related
illness.

Treatment
Heat cramps
The care of heat cramps includes placing the individual at rest in a cool environment, while giving cool
water with a teaspoon of salt per quart, or a commercial sports drink. Usually rest and liquids are all that
is needed for the patient to recover. Mild stretching
and massaging of the muscle area follows once the
condition improves. The individual should not take
salt tablets, since this may actually worsen the condition. When the cramps stop, the person can usually
start activity again if there are no other signs of illness.
The individual needs to continue drinking fluids and
should be watched carefully for further signs of heatrelated illnesses.
Heat exhaustion
The individual suffering from heat exhaustion
should stop all physical activity and move immediately
to a cool place out of the sun, preferably a cool, airconditioned location. She or he should then lay down
with feet slightly elevated, remove or loosen clothing,
and drink cold (but not iced), slightly salty water
or commercial sports drink. Rest and replacement
of fluids and salt is usually all the treatment that is
needed, and hospitalization is rarely required.
Following rehydration, the person usually recovers
rapidly.
Heat stroke
Simply moving the individual afflicted with heat
stroke to a cooler place is not enough to reverse the
internal overheating. Emergency medical assistance
1728

KEY TERMS
Convulsions—Also termed seizures; a sudden violent contraction of a group of muscles.
Electrolytes—An element or compound that when
melted or dissolved in water dissociates into ions
and is able to conduct an electrical current. Careful
and regular monitoring of electrolytes and intravenous replacement of fluid and electrolytes are part
of the acute care in many illnesses.
Rehydration—The restoration of water or fluid to a
body that has become dehydrated.

should be called immediately. While waiting for help
to arrive, quick action to lower body temperature
must take place. Treatment involves getting the victim
to a cool place, loosening clothes or undressing the
heat stroke victim, and allowing air to circulate
around the body. The next important step is wrapping
the individual in wet towels or clothing, and placing
ice packs in areas with the greatest blood supply.
These areas include the neck, under the arm and
knees, and in the groin. Once the patient is under
medical care, cooling treatments may continue as
appropriate. The victim’s body temperature will be
monitored constantly to guard against overcooling.
Breathing and heart rate will be monitored closely,
and fluids and electrolytes will be replaced intravenously. Anti-convulsant drugs may be given. After
severe heat stroke, bed rest may be recommended for
several days.

Prognosis
Prompt treatment for heat cramps is usually very
effective with the individual returning to activity thereafter. Treatment of heat exhaustion usually brings full
recovery in one to two days. Heatstroke is a very
serious condition and its outcome depends upon general health and age. Due to the high internal temperature of heat stroke, permanent damage to internal
organs is possible.

Prevention
Because heat cramps, heat exhaustion, and heat
stroke have a cascade effect on each other, the prevention of the onset of all heat disorders is similar. Avoid
strenuous exercise when it is very hot. Individuals
exposed to extreme heat conditions should drink
plenty of fluids. Wearing light and loose-fitting
GALE ENCYCLOPEDIA OF MEDICINE

sensation in the affected area. Low blood circulation may
contribute to heat-related injuries. Heat treatments also
should not be used on individuals afflicted with heart,
lung, or kidney diseases. Deep heat treatments should
not be used on areas above the eye, heart, or on a pregnant patient. Deep heat treatments over areas with metal
surgical implants should be avoided in case of rapid
temperature increase and subsequent injury.



Conduction is the transfer of heat between two
objects in direct contact with each other.

Resources



Conversion is the transition of one form of energy to
heat.



Radiation involves the transmission and absorption
of electromagnetic waves to produce a heating effect.



Convection occurs when a liquid or gas moves past
a body part creating heat.

Description
There are four different ways to convey heat:

OTHER

Griffith, H. Winter. ‘‘Complete Guide to Symptoms, Illness
& Surgery.’’ ThriveOnline. <http://
thriveonline.oxygen.com>.

Jeffrey P. Larson, RPT
Hot packs, water bottles, and heating pads

Heat exhaustion see Heat disorders

Heat treatments
Definition
Heat treatments are applications of therapeutic
thermal agents to specific body areas experiencing
injury or dysfunction.

Purpose
The general purpose of a heat treatment is to
increase the extensibility of soft tissues, remove toxins
from cells, enhance blood flow, increase function of
the tissue cells, encourage muscle relaxation, and help
relieve pain. There are two types of heat treatments:
superficial and deep. Superficial heat treatments apply
heat to the outside of the body. Deep heat treatments
direct heat toward specific inner tissues through ultrasound or by electric current. Heat treatments are
beneficial prior to exercise, providing a warm-up effect
to the soft tissues involved.

Precautions
Heat treatments should not be used on individuals
with circulation problems, heat intolerance, or lack of
GALE ENCYCLOPEDIA OF MEDICINE

Hot packs are a very common form of heat treatment utilizing conduction as a form of heat transfer.
Moist heat packs are readily available in most hospitals, physical therapy centers, and athletic training
rooms. Treatment temperature should not exceed
131  F (55  C). The pack is used over multiple layers
of toweling to achieve a comfortable warming effect
for approximately 30 minutes. More recently, several
manufacturers have developed packs that may be
warmed in a microwave over a specified amount of
time prior to use.
Hot-water bottles are another form of superficial
heat treatment. The bottles are filled half way with hot
water between 115–125  F (46.1–52  C). Covered by a
protective toweling, the hot-water bottle is placed
on the treatment area and left until the water has
cooled off.
Electrical heating pads continue to be used, however because of the need for an electrical outlet, safety
and convenience become an issue.
Paraffin
Paraffin, a conductive form of superficial heat, is
often used for heating uneven surfaces of the body
such as the hands. It consists of melted paraffin wax
and mineral oil. Paraffin placed in a small bath unit
becomes solid at room temperature and is used as a
liquid heat treatment when heated at 126–127.4  F
(52–53  C). The most common form of paraffin
1729

Heat treatments

clothing in hot weather is important, regardless of the
activity. It is important to consume water often and
not to wait until thirst develops. If perspiration is
excessive, fluid intake should be increased. When
urine output decreases, fluid intake should also
increase. Eating lightly salted foods can help replace
salts lost through perspiration. Ventilation in any
working areas in warm weather must be adequate.
This can be achieved as simply as opening a window
or using an electric fan. Proper ventilation will promote adequate sweat evaporation to cool the skin.
Sunblocks and sunscreens with a protection factor
of 15 (SPF 15) can be very helpful when one is exposed
to extreme direct sunlight.

Heat treatments

application is called the dip and wax method. In this
technique, the patient will dip eight to 12 times and
then the extremity will be covered with a plastic bag
and a towel for insulation. Most treatment sessions are
about 20 minutes.
Hydrotherapy
Hydrotherapy is used in a form of heat treatment
for many musculoskeletal disorders. The hydrotherapy tanks and pools are all generally set at warm
temperatures, never exceeding 150  F (65.6  C).
Because the patient often performs resistance exercises
while in the water, higher water temperatures become
a concern as the treatment becomes more physically
draining. Because of this, many hydrotherapy baths
are now being set at 95–110  F (35–43.3  C). There are
also units available with moveable turbine jets, which
provide a light massage effect. Hydrotherapy is helpful
as a warm-up prior to exercise.
Fluidotherapy
Fluidotherapy is a form of heat treatment developed in the 1970s. It is a dry heat modality consisting
of cellulose particles suspended in air. Units come in
different sizes and some are restricted to only treating
a hand or foot. The turbulence of the gas-solid mixture
provides thermal contact with objects that are immersed
in the medium. Temperatures of this treatment range
from 110–123  F (43.3–50.5  C). Fluidotherapy allows
the patient to exercise the limb during the treatment,
and also massages the limb, increasing blood flow.
Ultrasound
Ultrasound heat treatments penetrate the body to
provide relief to inner tissue. Ultrasound energy comes
from the acoustic or sound spectrum and is undetectable to the human ear. By using conducting agents
such as gel or mineral oil, the ultrasound transducer
warms areas of the musculoskeletal system Some areas
of the musculoskeletal system absorb ultrasound
better that others. Muscle tissue and other connective
tissue such as ligaments and tendons absorb this form
of energy very well, however fat absorbs to a much
lesser degree. Ultrasound has a relatively longlasting
effect, continuing up to one hour.
Diathermy
Diathermy is another deep heat treatment. An
electrode drum is used to apply heat to an affected
area. It consists of a wire coil surrounded by dead
space and other insulators such as a plastic housing.
Plenty of toweling must be layered between the unit
1730

and the patient. This device is unique in that it utilizes
the basis of a magnetic field on connective tissues.
One advantage of diathermy over various other heat
treatments is that fat does resist an electrical field,
which is not the case with a magnetic field. It is
found to be helpful with those experiencing chronic
low back pain and muscle spasms. Prior to ultrasound
technology, diathermy was a popular heat therapy of
the 1940s–1960s.

Preparation
Before administering any form of heat treatment,
heat sensitivity is accessed and the skin over the
affected area is cleansed. When a patient is undergoing
any form of heat treatment, supervision should always
be present especially in the treatment of hydrotherapy.

Aftercare
Once the heat treatment has been completed, any
symptoms of dizziness and nausea should be noted
and documented along with any skin irritations or
discoloring not present prior to the heat treatment. A
one hour interval between treatments should be
adhered to in order to avoid restriction of blood flow.

Risks
All heat treatments have the potential of tissue
damage resulting from excessive temperatures.
Proper insulation and treatment duration should be
carefully administered for each method. Overexposure
during a superficial heat treatment may result in redness, blisters, burns, or reduced blood circulation.
During ultrasound therapy, excessive treatment over
bony areas with little soft tissue (such as hand, feet,
and elbow) can cause excessive heat resulting in pain
and possible tissue damage. Exposure to the electrode
drum during diathermy may produce hot spots.
Resources
ORGANIZATIONS

American Physical Therapy Association. 1111 North
Fairfax St., Alexandria, Virginia 22314. (800) 999-2782.
<https://www.apta.org>.

Jeffrey P. Larson, RPT

Heatstroke see Heat disorders
Heavy menstruation see Dysfunctional
uterine bleeding
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Heavy metal poisoning is the toxic accumulation
of heavy metals in the soft tissues of the body.

Description
Heavy metals are chemical elements that have a
specific gravity (a measure of density) at least five
times that of water. The heavy metals most often implicated in accidental human poisoning are lead, mercury,
arsenic, and cadmium. More recently, thallium has
gained some attention in the media as the poison used
in several murder cases in the 1990s. Some heavy
metals, such as zinc, copper, chromium, iron, and manganese, are required by the body in small amounts, but
these same elements can be toxic in larger quantities.
Heavy metals may enter the body in food, water,
or air, or by absorption through the skin. Once in the
body, they compete with and displace essential minerals such as zinc, copper, magnesium, and calcium, and
interfere with organ system function. People may
come in contact with heavy metals in industrial
work, pharmaceutical manufacturing, and agriculture. Children may be poisoned as a result of playing
in contaminated soil. Lead poisoning in adults has been
traced to the use of lead-based glazes on pottery
vessels intended for use with food, and contamination
of Ayurvedic and other imported herbal remedies.
Arsenic and thallium have been mixed with food or
beverages to attempt suicide or poison others.
Another form of mercury poisoning that is seen
more and more frequently in the United States is selfinjected mercury under the skin. Some boxers inject
themselves with mercury in the belief that it adds
muscle bulk. Metallic mercury is also used in folk
medicine or religious rituals in various cultures.
These practices increase the risk of mercury poisoning
of children in these ethnic groups or subcultures.

Causes and symptoms
Symptoms will vary, depending on the nature and
the quantity of the heavy metal ingested. Patients may
complain of nausea, vomiting, diarrhea, stomach pain,
headache, sweating, and a metallic taste in the mouth.
Depending on the metal, there may be blue-black lines
in the gum tissues. In severe cases, patients exhibit
obvious impairment of cognitive, motor, and language
skills. The expression ‘‘mad as a hatter’’ comes from
the mercury poisoning prevalent in 17th-century
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Heavy metal poisoning may be detected using
blood and urine tests, hair and tissue analysis, or
x ray. The diagnosis is often overlooked, however,
because many of the early symptoms of heavy metal
poisoning are nonspecific. The doctor should take a
thorough patient history with particular emphasis on
the patient’s occupation.
In childhood, blood lead levels above 80 ug/dL
generally indicate lead poisoning, however, significantly lower levels (>30 ug/dL) can cause mental
retardation and other cognitive and behavioral problems in affected children. The Centers for Disease
Control and Prevention considers a blood lead level
of 10 ug/dL or higher in children a cause for concern.
In adults, symptoms of lead poisoning are usually seen
when blood lead levels exceed 80 ug/dL for a number
of weeks.
Blood levels of mercury should not exceed 3.6 ug/
dL, while urine levels should not exceed 15 ug/dL.
Symptoms of mercury poisoning may be seen when
mercury levels exceed 20 ug/dL in blood and 60 ug/dL
in urine. Mercury levels in hair may be used to gauge
the severity of chronic mercury exposure.
Since arsenic is rapidly cleared from the blood,
blood arsenic levels may not be very useful in diagnosis. Arsenic in the urine (measured in a 24-hour collection following 48 hours without eating seafood) may
exceed 50 ug/dL in people with arsenic poisoning. If
acute arsenic or thallium poisoning is suspected, an
x ray may reveal these substances in the abdomen
(since both metals are opaque to x rays). Arsenic
may also be detected in the hair and nails for months
following exposure.
Cadmium toxicity is generally indicated when
urine levels exceed 10 ug/dL of creatinine and blood
levels exceed 5 ug/dL.
Thallium poisoning often causes hair loss (alopecia), numbness, and a burning sensation in the skin
as well as nausea, vomiting, and dizziness. As little as
15–20 mg of thallium per kilogram of body weight is
fatal in humans; however, smaller amounts can cause
severe damage to the nervous system.

Treatment
When heavy metal poisoning is suspected, it
is important to begin treatment as soon as possible
1731

Heavy metal poisoning

Heavy metal poisoning

France among hatmakers who soaked animal hides
in a solution of mercuric nitrate to soften the hair.

Heavy metal poisoning

to minimize long-term damage to the patient’s nervous system and digestive tract. Heavy metal poisoning is considered a medical emergency, and the
patient should be taken to a hospital emergency
room.
The treatment for most heavy metal poisoning is
chelation therapy. A chelating agent specific to the
metal involved is given either orally, intramuscularly,
or intravenously. The three most common chelating
agents are calcium disodium edetate, dimercaprol
(BAL), and penicillamine. The chelating agent encircles and binds to the metal in the body’s tissues, forming a complex; that complex is then released from the
tissue to travel in the bloodstream. The complex is
filtered out of the blood by the kidneys and excreted
in the urine. This process may be lengthy and painful, and typically requires hospitalization. Chelation
therapy is effective in treating lead, mercury, and
arsenic poisoning, but is not useful in treating
cadmium poisoning. To date, no treatment has been
proven effective for cadmium poisoning. Thallium
poisoning is treated with a combination of Prussian
blue (potassium ferric hexacyanoferrate) and a diuretic,
because about 35% of it is excreted in the urine;
however, if treatment is not started within 72 hours of
ingesting the poisoning, damage to the patient’s nervous system may be permanent.
In cases of acute mercury, arsenic, or thallium
ingestion, vomiting may be induced. Activated charcoal may be given in cases of thallium poisoning.
Washing out the stomach (gastric lavage) may also
be useful. The patient may also require treatment
such as intravenous fluids for such complications of
poisoning as shock, anemia, and kidney failure.
Patients who have taken arsenic, thallium, or
mercury in a suicide attempt will be seen by a psychiatrist as part of emergency treatment.

Prognosis
The chelation process can only halt further effects
of the poisoning; it cannot reverse neurological
damage already sustained.

Prevention
Because arsenic and thallium were commonly
used in rat and insect poisons at one time, many
countries have tried to lower the rate of accidental
poisonings by banning the use of heavy metals in
pest control products. Thallium was banned in the
United States as a rodent poison in 1984. As a result,
almost all recent cases of arsenic and thallium
1732

KEY TERMS
Alopecia—Loss of hair.
Chelation—The process by which a molecule
encircles and binds to a metal and removes it
from tissue.
Heavy metal—One of 23 chemical elements that
has a specific gravity (a measure of density) at least
five times that of water.
Prussian blue—The common name of potassium
ferric hexacyanoferrate, a compound approved in
the United States for treatment of thallium poisoning. Prussian blue gets its name from the fact that it
was first used by artists in 1704 as a dark blue
pigment for oil paints. It has also been used in
laundry bluing and fabric printing.

poisoning in the United States were deliberate rather
than accidental.
Because exposure to heavy metals is often an
occupational hazard, protective clothing and respirators should be provided and worn on the job.
Protective clothing should then be left at the work
site and not worn home, where it could carry toxic
dust to family members. Industries are urged to reduce
or replace the heavy metals in their processes wherever
possible. Exposure to environmental sources of lead,
including lead-based paints, plumbing fixtures, vehicle
exhaust, and contaminated soil, should be reduced or
eliminated.
People who use Ayurvedic or traditional Chinese
herbal preparations as alternative treatments for various illnesses should purchase them only from reliable
manufacturers.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Poisoning.’’ Section 23, Chapter 307 In The
Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychiatric Emergencies.’’ Section 15, Chapter 194
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Wilson, Billie A., Margaret T. Shannon, and Carolyn L.
Stang. Nurses Drug Guide 2000. Stamford, CT:
Appleton & Lange, 2000.
GALE ENCYCLOPEDIA OF MEDICINE

Boyarsky, Igor, DO, and Adrain D. Crisan, MD. ‘‘Toxicity,
Thallium.’’ eMedicine August 3, 2004. <http://www
.emedicine.com/emerg/topic926.htm>.
Centers for Disease Control and Prevention (CDC). ‘‘Adult
Blood Lead Epidemiology and Surveillance—United
States, 2002.’’ Morbidity and Mortality Weekly Report
53 (July 9, 2004): 578–582.
Counter, S. A., and L. H. Buchanan. ‘‘Mercury Exposure in
Children: A Review.’’ Toxicology and Applied
Pharmacology 198 (July 15, 2004): 209–230.
Ferner, David J., MD. ‘‘Toxicity, Heavy Metals.’’ eMedicine
May 25, 2001. <http://www.emedicine.com/EMERG/
topic237.htm>.
Prasad, V. L. ‘‘Subcutaneous Injection of Mercury:
‘Warding Off Evil’.’’ Environmental Health Perspectives
111 (September 2004): 1326–1328.
Schilling, U., R. Muck, and E. Heidemann. ‘‘Lead Poisoning
after Ingestion of Ayurvedic Drugs.’’ [in German]
Medizinische Klinik 99 (August 15, 2004):
476–480.
Thompson, D. F., and E. D. Callen. ‘‘Soluble or Insoluble
Prussian Blue for Radiocesium and Thallium
Poisoning?’’ Annals of Pharmacotherapy 38 (September
2004): 1509–1514.
ORGANIZATIONS

American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814. (301)
657-3000. <http://www.ashp.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
Food and Drug Administration. Office of Inquiry and
Consumer Information. 5600 Fisher Lane, Room
12-A-40, Rockville, MD 20857. (301) 827-4420.
<http://www.fda.gov/fdahomepage.html>.
National Institutes of Health. National Institute of
Environmental Health Sciences Clearinghouse.
EnviroHealth, 2605 Meridian Parkway, Suite 115,
Durham, NC 27713. (919) 361-9408.

Bethany Thivierge
Rebecca J. Frey, PhD

Heel spurs
Definition
A heel spur is a bony projection on the sole (plantar) region of the heel bone (also known as the calcaneous). This condition may accompany or result from
severe cases of inflammation to the structure called
plantar fascia. This associated plantar fascia is a
GALE ENCYCLOPEDIA OF MEDICINE

fibrous band of connective tissue on the sole of the
foot, extending from the heel to the toes.

Description
Heel spurs are a common foot problem resulting
from excess bone growth on the heel bone. The bone
growth is usually located on the underside of the heel
bone, extending forward to the toes. One explanation
for this excess production of bone is a painful tearing
of the plantar fascia connected between the toes and
heel. This can result in either a heel spur or an inflammation of the plantar fascia, medically termed plantar
fascitis. Because this condition is often correlated to a
decrease in the arch of the foot, it is more prevalent
after the age of six to eight years, when the arch is fully
developed.

Causes and symptoms
One frequent cause of heel spurs is an abnormal
motion and mal-alignment of the foot called pronation. For the foot to function properly, a certain
degree of pronation is required. This motion is defined
as an inward action of the foot, with dropping of the
inside arch as one plants the heel and advances the
weight distribution to the toes during walking. When
foot pronation becomes extreme from the foot turning
in and dropping beyond the normal limit, a condition
known as excessive pronation creates a mechanical
problem in the foot. In some cases the sole or bottom
of the foot flattens and becomes unstable because
of this excess pronation, especially during critical
times of walking and athletic activities. The portion
of the plantar fascia attached into the heel bone or
calcaneous begins to stretch and pull away from the
heel bone.
At the onset of this condition, pain and swelling
become present, with discomfort particularly noted
as pushing off with the toes occurs during walking.
This movement of the foot stretches the fascia
that is already irritated and inflamed. If this condition is allowed to continue, pain is noticed around
the heel region because of the newly formed bone,
in response to the stress. This results in the development of the heel spur. It is common among
athletes and others who run and jump a significant
amount.
An individual with the lower legs angulating
inward, a condition called genu valgum or ‘‘knock
knees,’’ can have a tendency toward excessive pronation. As a result, this too can lead to a fallen
arch resulting in plantar fascitis and heel spurs.
1733

Heel spurs

PERIODICALS

Heel spurs

Diagnosis
A thorough medical history and physical exam
by a physician is always necessary for the proper diagnosis of heel spurs and other foot conditions. X rays of
the heel area are helpful, as excess bone production
will be visible.

Treatment
Conservative

llustration of bony projection, a spur, which developed from
chronic irritation. (Photo Researchers. Reproduced by
permission.)

Women tend to have more genu valgum than men
do. Heel spurs can also result from an abnormally
high arch.
Other factors leading to heel spurs include a sudden increase in daily activities, an increase in weight, or
a change of shoes. Dramatic increase in training intensity or duration may cause plantar fascitis. Shoes that
are too flexible in the middle of the arch or shoes that
bend before the toe joints will cause an increase
in tension in the plantar fascia and possibly lead to
heel spurs.
The pain this condition causes forces an individual to attempt walking on his or her toes or ball of the
foot to avoid pressure on the heel spur. This can lead
to other compensations during walking or running
that in turn cause additional problems to the ankle,
knee, hip, or back.
1734

Heel spurs and plantar fascitis are usually controlled with conservative treatment. Early intervention includes stretching the calf muscles while
avoiding re-injuring the plantar fascia. Decreasing or
changing activities, losing excess weight, and improving the proper fitting of shoes are all important measures to decrease this common source of foot pain.
Modification of footwear includes shoes with a raised
heel and better arch support. Shoe orthotics recommended by a healthcare professional are often very
helpful in conjunction with exercises to increase
strength of the foot muscles and arch. The orthotic
prevents excess pronation and lengthening of the plantar fascia and continued tearing of this structure.
To aid in this reduction of inflammation, applying
ice for 10–15 minutes after activities and use of antiinflammatory medication can be helpful. Physical
therapy can be beneficial with the use of heat modalities, such as ultrasound that creates a deep heat and
reduces inflammation. If the pain caused by inflammation is constant, keeping the foot raised above
the heart and/or compressed by wrapping with an
ace bandage will help.
Corticosteroid injections are also frequently used
to reduce pain and inflammation. Taping can help
speed the healing process by protecting the fascia
from reinjury, especially during stretching and
walking.
Heel surgery
When chronic heel pain fails to respond to conservative treatment, surgical treatment may be necessary. Heel surgery can provide relief of pain and
restore mobility. The type of procedure used is
based on examination and usually consists of releasing the excessive tightness of the plantar fascia, called
a plantar fascia release. Depending on the presence
of excess bony build up, the procedure may or may
not include removal of heel spurs. Similar to other
surgical interventions, there are various modifications and surgical enhancements regarding surgery
of the heel.
GALE ENCYCLOPEDIA OF MEDICINE

Calcaneous—The heel bone.
Genu valgum—Deformity in which the legs are
curved inward so that the knees are close together,
nearly or actually knocking as a person walks with
ankles widely apart of each other.
Plantar fascia—A tough fibrous band of tissue surrounding the muscles of the sole of the foot. Also
called plantar aponeurosis.
Pronation—The lowering or descending of the
inner edge of the foot by turning the entire foot
outwards.

Alternative treatment
Acupuncture and accupressure have been used to
address the pain of heel spurs, in addition to using
friction massage to help break up scar tissue and
delay onset of bony formations.

Prognosis
Usually, heel spurs are curable with conservative
treatment. If not, heel spurs are curable with surgery.
About 10% of those that continue to see a physician
for plantar fascitis have it for more than a year. If there
is limited success after approximately one year of
conservative treatment, patients are often advised to
have surgery.

Prevention
To prevent this condition, wearing shoes with
proper arches and support is very important. Proper
stretching is always a necessity, especially when there
is an increase in activities or a change in running
technique. It is not recommended to attempt working
through the pain, as this can change a mild case of
heel spurs and plantar fascitis into a long lasting and
painful episode of this condition.

Heimlich maneuver
Definition
The Heimlich maneuver is an emergency procedure for removing a foreign object lodged in the
airway that is preventing a person from breathing.

Purpose
Every year about 3,000 adults die because they
accidentally inhale rather than swallow food. The
food gets stuck and blocks their trachea, making
breathing impossible. Death follows rapidly unless
the food or other foreign material can be displaced
from the airway. This condition is so common it has
been nicknamed the ‘‘cafe coronary.’’
In 1974 Dr. Henry Heimlich first described an
emergency technique for expelling foreign material
blocking the trachea. This technique, now called the
Heimlich maneuver or abdominal thrusts, is simple
enough that it can be performed immediately by anyone trained in the maneuver. The Heimlich maneuver
is a standard part of all first aid courses.
The theory behind the Heimlich maneuver is
that by compressing the abdomen below the level
of the diaphragm, air is forced under pressure out
of the lungs dislodging the obstruction in the trachea
and bringing the foreign material back up into the
mouth.
The Heimlich maneuver is used mainly when solid
material like food, coins, vomit, or small toys are
blocking the airway. There has been some controversy
about whether the Heimlich maneuver is appropriate
to use routinely on near-drowning victims. After
several studies of the effectiveness of the Heimlich
maneuver on reestablishing breathing in near-drowning
victims, the American Red Cross and the American
Heart Association both recommend that the Heimlich
maneuver be used only as a last resort after traditional
airway clearance techniques and cardiopulmonary
resuscitation (CPR) have been tried repeatedly and
failed or if it is clear that a solid foreign object is
blocking the airway.

Resources
ORGANIZATIONS

American Orthopedic Foot and Ankle Society. 222 South
Prospect, Park Ridge, IL 60068.
American Podiatry Medical Association. 9312 Old
Georgetown Road, Bethesda, MD 20814.

Jeffrey P. Larson, RPT
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Incorrect application of the Heimlich maneuver
can damage the chest, ribs, and internal organs
of the person on whom it is performed. People may
also vomit after being treated with the Heimlich
maneuver.
1735

Heimlich maneuver

KEY TERMS

Heimlich maneuver

Description
The Heimlich maneuver can be performed on all
people. Modifications are necessary if the choking
victim is very obese, pregnant, a child, or an infant.
Indications that a person’s airway is blocked
include:


The person can not speak or cry out.



The person’s face turns blue from lack of oxygen.



The person desperately grabs at his or her throat.



The person has a weak cough, and labored breathing
produces a high-pitched noise.



The person does all of the above, then becomes
unconscious.

Object
dislodged

A quick
upward
thrust
with fist

Performing the Heimlich maneuver on adults
To perform the Heimlich maneuver on a conscious adult, the rescuer stands behind the victim.
The victim may either be sitting or standing. The
rescuer makes a fist with one hand, and places it,
thumb toward the victim, below the rib cage and
above the waist. The rescuer encircles the victim’s
waist, placing his other hand on top of the fist.
In a series of 6–10 sharp and distinct thrusts
upward and inward, the rescuer attempts to develop
enough pressure to force the foreign object back up the
trachea. If the maneuver fails, it is repeated. It is
important not to give up if the first attempt fails. As
the victim is deprived of oxygen, the muscles of the
trachea relax slightly. Because of this loosening, it is
possible that the foreign object may be expelled on a
second or third attempt.
If the victim is unconscious, the rescuer should
lay him or her on the floor, bend the chin forward,
make sure the tongue is not blocking the airway,
and feel in the mouth for foreign objects, being
careful not to push any farther into the airway.
The rescuer kneels astride the victim’s thighs and
places his fists between the bottom of the victim’s
breastbone and the navel. The rescuer then executes
a series of 6–10 sharp compressions by pushing
inward and upward.
After the abdominal thrusts, the rescuer repeats
the process of lifting the chin, moving the tongue,
feeling for and possibly removing the foreign material.
If the airway is not clear, the rescuer repeats the
abdominal thrusts as often as necessary. If the foreign
object has been removed, but the victim is not breathing, the rescuer starts CPR.
1736

The Heimlich maneuver
To perform the Heimlich maneuver on a conscious adult (as
illustrated above), the rescuer stands behind the victim and
encircles his waist. The rescuer makes a fist with one hand
and places the other hand on top, positioned below the rib
cage and above the waist. The rescuer then applies pressure
by a series of upward and inward thrusts to force the foreign
object back up the victim’s trachea. (Illustration by Electronic
Illustrators Group.)

Performing the Heimlich maneuver under special
circumstances
OBVIOUSLY

PREGNANT

AND

VERY

OBESE

PEOPLE. The

main difference in performing the
Heimlich maneuver on this group of people is in the
placement of the fists. Instead of using abdominal
GALE ENCYCLOPEDIA OF MEDICINE

CHILDREN. The technique in children over one
year of age is the same as in adults, except that the
amount of force used is less than that used with adults
in order to avoid damaging the child’s ribs, breastbone, and internal organs.
INFANTS UNDER ONE YEAR OLD. The rescuer sits
down and lays the infant along his or her forearm
with the infant’s face pointed toward the floor. The
rescuer’s hand supports the infant’s head, and his or
her forearm rests on his or her own thigh for additional support. Using the heel of the other hand, the
rescuer administers four or five rapid blows to the
infant’s back between the shoulder blades.

After administering the back blows, the rescuer
sandwiches the infant between his or her arms, and
turns the infant over so that the infant is lying face up
supported by the opposite arm. Using the free hand,
the rescuer places the index and middle finger on the
center of the breastbone and makes four sharp chest
thrusts. This series of back blows and chest thrusts is
alternated until the foreign object is expelled.
SELF-ADMINISTRATION
OF
THE
HEIMLICH
MANEUVER. To apply the Heimlich maneuver to one-

self, one should make a fist with one hand and place it
in the middle of the body at a spot above the navel and
below the breastbone, then grasp the fist with the other
hand and push sharply inward and upward. If this
fails, the victim should press the upper abdomen over
the back of a chair, edge of a table, porch railing or
something similar, and thrust up and inward until the
object is dislodged.

KEY TERMS
Diaphragm—The thin layer of muscle that separates the chest cavity containing the lungs and
heart from the abdominal cavity containing the
intestines and digestive organs.
Trachea—The windpipe. A tube extending from
below the voice box into the chest where it splits
into two branches, the bronchi, that lead to each lung.

severity of the choking episode, the choking victim
may need to be taken to a hospital emergency room.

Risks
Incorrectly applied, the Heimlich maneuver can
break bones or damage internal organs. In infants, the
rescuer should never attempt to sweep the baby’s
mouth without looking to remove foreign material.
This is likely to push the material farther down the
trachea.

Normal results
In many cases the foreign material is dislodged
from the throat, and the choking victim suffers no
permanent effects of the episode. If the foreign material
is not removed, the person dies from lack of oxygen.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Tish Davidson, A.M.

Preparation
Any lay person can be trained to perform the
Heimlich maneuver. Knowing how may save someone’s life. Before doing the maneuver, it is important
to determine if the airway is completely blocked. If the
person choking can talk or cry, Heimlich maneuver is
not appropriate. If the airway is not completely
blocked, the choking victim should be allowed to try
to cough up the foreign object on his or her own.

Aftercare
Many people vomit after being treated with the
Heimlich maneuver. Depending on the length and
GALE ENCYCLOPEDIA OF MEDICINE

Helicobacter pylori infection see
Helicobacteriosis

Helicobacteriosis
Definition
Helicobacteriosis refers to infection of the gastrointestinal tract with the bacteria, Helicobacter pylori
(H. pylori). While there are other rarer strains of
Helicobacter species that can infect humans, only
1737

Helicobacteriosis

thrusts, chest thrusts are used. The fists are placed
against the middle of the breastbone, and the motion
of the chest thrust is in and downward, rather than
upward. If the victim is unconscious, the chest thrusts
are similar to those used in CPR.

Helicobacteriosis

H. pylori has been convincingly shown to be a cause of
disease in humans. The organism was first documented to cause injury to the stomach in 1983, by two
researchers in Australia, who ingested the organism
to prove their theory. Since then, H. pylori has been
shown to be the main cause of ulcer disease, and has
revolutionized the treatment of peptic ulcer disease.
It also is believed to be linked to various cancers of
the stomach.

Description
H. pylori is a gram-negative, spiral-shaped organism, that contains flagella (tail-like structures) and
other properties. In addition to flagella, which help
the organism to move around in the liquid mucous
layer of the stomach, H. pylori also produces an
enzyme called urease, that protects it from gastric
acid present in the stomach. As the production of
this enzyme is relatively unusual, new diagnostic tests
have enabled rapid identification of the bacteria.
H. pylori also produces two other chemicals: a
cytotoxin called vacA, and a protein known as cagA.
Patients with ulcer disease are more likely to produce
the cytotoxin (vacA). The cagA protein not only
occurs frequently in ulcer disease but also in cancer.
It is still not known how these substances enable
H. pylori to cause disease.

In about 15% of infected persons, ulcer disease
develops either in the stomach or duodenum. Why
some develop ulcer disease and others do not remains
unclear. Ulcer symptoms are characterized by upper
abdominal pain that is typically of a burning or
‘‘gnawing’’ type, and usually is rapidly relieved by
antacids or food.
Acid secretion increases in most patients with
duodenal ulcers. This increase returns to normal
once H. pylori is eliminated. It is now known that
elimination of the bacteria will substantially decrease
the risk of recurrent bouts of ulcer disease in the vast
majority of patients. In fact, a 2003 report showed that
by eradicating H. pylori, ulcer bleeding rarely recurs.
In the last decade it has been shown that H. pylori
is not only the prime cause of ulcer disease of the
stomach and duodenum, but is also strongly associated with various tumors of the stomach. Bacterial
infection is nine times more common in patients with
cancer of the stomach, and seven times more common
in those with lymphoma of the stomach (tumor of the
lymphatic tissue), called a MALT tumor. It is believed
that the prolonged inflammation leads to changes in
cell growth and tumors. Eliminating H. pylori can lead
to regression of some tumors.
In addition to the above damage caused by
H. pylori, some individuals lose normal gastric function, such as the ability to absorb vitamin B12.

Causes and symptoms
Infection with H. pylori is largely dependent on
two factors; age and income status. The bacteria is
acquired mainly in childhood, especially in areas of
poor hygiene or overcrowding. H. pylori is two to
three times more prevalent in developing, non-industrialized countries. In the United States for example,
the organism is believed to be present in about one
third of the population.
The exact way in which H. pylori gets passed from
one individual to another is uncertain, but person
to person transmission is most likely. In most cases,
children are felt to be the source of spread. Reinfection
of those who have been cured has been documented,
especially in areas of overcrowding.
The bacteria is well adapted to survival within the
stomach. Not only does it survive there for years, but
once infection begins, a form of chronic inflammation
(chronic gastritis) always develops. In most individuals, initial infection causes little or no symptoms;
however, some individuals such as the original
researchers who ingested the bacteria, wind up with
abdominal pain and nausea.
1738

Diagnosis
There are basically two types of tests to identify
infection: one group is ‘‘invasive’’ in that it involves
the use of an endoscopy to obtain biopsy specimens
for evaluation, while the other ‘‘noninvasive’’ methods depend on blood or breath samples. Invasive
tests can be less accurate because of technical limitations: the biopsy may miss the area where the bacteria
hides.
Invasive studies make use of tissue obtained
by endoscopic biopsy to identify the organism. The
bacteria can be searched for in pieces of biopsy tissue
or grown (cultured) from the specimen. However,
H. pylori is not easy to culture. Another method uses
the bacteria’s production of the enzyme urease. Biopsy
specimens are placed on a card that changes color if
urease is present. Results often are available within a
few minutes, but can take up to 24 hours.
Noninvasive tests are of two types: blood tests and
breath test. Blood tests measure antibodies to make
a diagnosis accurately within minutes. This can be
done immediately in the doctor’s office. In addition,
GALE ENCYCLOPEDIA OF MEDICINE

Antibiotic—A medication that is designed to kill or
weaken bacteria.
Endoscope, Endoscopy—An Endoscope as used in
the field of Gastroenterology is a thin flexible tube
that uses a lens or miniature camera to view various
areas of the gastrointestinal tract. When the procedure is performed to examine certain organs such
as the bile ducts or pancreas, the organs are not
viewed directly, but rather indirectly through the
injection of x ray. The performance of an exam
using an endoscope is referred by the general term
endoscopy. Diagnosis through biopsies or other
means and therapeutic procedures can be done
with these instruments.

A light microscopic image of a stomach ulcer. Gastric
and duodenal ulcers are usually caused by infection with
the bacteria Helicobacter pylori. This bacterium is also
believed to be a cause of various cancers of the stomach.
(Photograph by J.L. Carson, Custom Medical Stock Photo.
Reproduced by permission.)

antibody levels can be measured several months after
treatment, to see if H. pylori has been eradicated.
The breath test uses radioactive or non-radioactive forms of a compound called urea, which the
patient drinks. The method that uses a radioactive
form urea is easier to perform, as the equipment is
commonly available in x-ray departments. Radiation
exposure is less than that of a chest x ray. The test that
uses non-radioactive urea is safer for children. A 2003
study in Brazil showed that the urea breath test and H.
pylori stool antigen test also worked well to detect the
bacteria in children. The breath test is the best way to
be sure of elimination of H. pylori. The test can be used
within 30 days after treatment. This is an advantage
over following antibody levels that take six months or
longer to diminish.

Treatment
H. pylori peptic ulcers are treated with drugs
to kill the bacteria, drugs to reduce stomach acid,
and drugs to protect the lining of the stomach. The
antibiotics most commonly used to kill the bacteria
are: amoxicillin, clarithromycin, metronidazole, and
tetracycline. Drugs used to reduce stomach acid
may be histamine blockers or proton pump inhibitors.
The most commonly used histamine blockers are:
GALE ENCYCLOPEDIA OF MEDICINE

Gram-negative—Refers to the property of many
bacteria in which they do not take or color with
Gram’s stain, a method which is used to identify
bacteria. Gram-positive bacteria that take up the
stain turn purple, while Gram-negative bacteria
which do not take up the stain turn red.

cimetidine, famotidine, nizatidine, and ranitidine.
The most commonly used proton pump inhibitors
are: lansoprazole and omeprazole. The drug bismuth
subsalicylate (a component of Pepto-Bismol) is used to
protect the stomach lining.
The most common drug treatment is a two-week
course of treatment called triple therapy. This treatment regimen involves taking two antibiotics to kill the
bacteria and either an acid reducer or a stomach-lining
shield. This therapy has been shown to kill the bacteria, reduce ulcer symptoms, and prevent ulcer recurrence in over 90% of patients.
The main drawback of triple therapy is that some
patients find it difficult to follow because it often
requires taking as many as 20 pills a day. The antibiotics also may cause unpleasant side effects that
may make certain patients less likely to follow the
treatment protocol. These side effects include: dark
stools, diarrhea, dizziness, headache, a metallic taste
in the mouth, nausea, vomiting, and yeast infections in
women.

Prognosis
The elimination of H. pylori and cure of ulcer
disease is now possible in more than 90% of those
infected. The finding that most ulcers are due to an
1739

Helicobacteriosis

KEY TERMS

Hellerwork

infectious agent has brought a dramatic change in
treatment and outlook for those suffering from the
disease. Some patients will wind up with repeated
infection, but this is most common in overcrowded
areas.

Prevention
Attempts to develop a vaccine to protect against
infection may be worthwhile in areas where the
H. pylori infection rate and occurrence of cancer of
the stomach is high. Research has shown such a vaccine would likely be safe in humans, but a vaccine has
yet to be fully identified and developed as of mid-2003.

body’s structure for overall health, improvement of
posture, and reduction of physical and mental stress.

Purpose
Hellerwork improves posture and brings the
body’s natural structure into proper balance and
alignment. This realignment can bring relief from
general aches and pains; improve breathing; and
relieve physical and mental stress. Hellerwork has
also been used to treat such specific physical problems
as chronic back, neck, shoulder, and joint pain as well
as repetitive stress injuries, including carpal tunnel
syndrome. Hellerwork is also used to treat and prevent
athletic injuries.

Resources
PERIODICALS

‘‘Urea Breath, Stool Antigen Tests Work Well to Detect
H. Pylori in Children.’’ Health & Medicine Week
September 22, 2003: 315.
‘‘Vaccination Against H. Pylori Is an Achievable Goal.’’
Drug Week July 18, 2003: 153.
Worcester, Sharon. ‘‘Eradicating H. Pylori May Prevent
Bleeding Ulcers: No [Histamine. Sub2] Blockers
Needed.’’ Internal Medicine News September 15,
2003: 33.
OTHER

‘‘H. Pylori and Peptic Ulcer.’’ National Institutes of Health.
<http://www.niddk.nih.gov/health/digest/pubs/
hpylori/hpylori.htm>.
‘‘Management Strategies for Helicobacter pylori
Seropositive Patients with Dyspepsia.’’
<http://www.acponline.org/journals/annals/15feb97/
treatcounsel.htm>.
‘‘Moving closer to an ulcer vaccine.’’
<http://www.msnbc.com/news/161712.asp>.
‘‘Treating Stomach Ulcers and H. pylori Infection.’’
<http://www.aafp.org/patientinfo/ulcers.html>.
‘‘What Is Helicobacter pylori Infection?’’ Centers for
Disease Control. <http://www.cdc.gov/ncidod/aip/
aip_a2b.htm>.

Paul A. Johnson, Ed.M.
Teresa G. Odle

Description
Origins
Joseph Heller (1940– ) developed Hellerwork, a
system of structural integration patterned after
Rolfing. Although Heller received a degree in engineering and worked for NASA’s Jet Propulsion
Laboratory in Pasadena, CA, he became interested
in humanistic psychology in the 1970s. He spent
two years studying bioenergetics and Gestalt therapy
as well as studying under architect and futurist
Buckminster Fuller (1895–1983), flotation tank therapy developer John Lilly, family therapist Virginia
Satir, and body movement pioneer Judith Aston.
During this period, he trained for six years with
Dr. Ida P. Rolf (1896-1979), the founder of Rolfing,
and became a certified Rolfer in 1972. After Heller
developed his own system of bodywork, he founded
Hellerwork in 1979 and established a training facility
in Mt. Shasta, California, where he continues his
work.
Hellerwork is based largely on the principles of
Rolfing, in which the body’s connective tissue is
manipulated or massaged to realign and balance the
body’s structure. Because Heller believes that physical
realignment is insufficient, however, he expanded his
system to include movement education and verbal
dialogue as well as deep tissue massage.
Connective tissue massage

Hellerwork
Definition
Hellerwork is a system of bodywork that combines deep tissue massage, body movement education,
and verbal dialogue. It is designed to realign the
1740

The massage therapy aspect of Hellerwork is
designed to release the tension that exists in the
deep connective tissue, called fascia, and return it to
a normal alignment. The fascia is plastic and highly
adaptable; it can tighten and harden in response to the
general effects of gravity on the body, other ongoing
GALE ENCYCLOPEDIA OF MEDICINE

Born in Poland, Joseph Heller attended school in
Europe until age 16, when he immigrated to the United
States. Living in Los Angeles, he attended the California
Institute of Technology in Pasadena and graduated in 1962
with a degree in engineering. He worked for 10 years at the
National Aeronautics and Space Administration’s Jet
Propulsion Laboratory (JPL) in Pasadena as an aerospace
engineer. During his service at JPL, Heller became interested
in humanistic psychology. After leaving JPL in 1972, he
became director of Kairos, a center for human development
in Los Angeles. He spent two years studying bioenergetics
and gestalt. He also trained under Buckminster Fuller, flotation tank therapy developer John Lilly, self-esteem trainer
Virginia Satir, and body movement pioneer Judith Aston.

(AP/Wide World Photos. Reproduced by permission.)

physical stresses, negative attitudes and emotions, and
periodic physical traumas. One example of ongoing
physical stress is carrying a briefcase, which pulls
down the shoulder on one side of the body. Over
time, the connective tissue becomes hard and stiff;
the body becomes adapted to that position even
when the person is not carrying a briefcase. In trying
to adjust to the uneven weight distribution, the rest of
the body becomes unbalanced and out of proper
alignment.
Heller believes that as people age, more of these
stress and trauma patterns become ingrained in the
connective tissue, further throwing the body out of
alignment. As stress accumulates, the body shortens
and stiffens, a process commonly attributed to aging.
Hellerwork seeks to recondition the body and make
the connective tissue less rigid.
Movement education
The second component of Hellerwork, movement
education, trains patients in the proper physical
movements needed to keep the body balanced and
correctly aligned. Movement education focuses on
common actions, such as sitting, standing, and walking.
GALE ENCYCLOPEDIA OF MEDICINE

He became a certified Rolfer in 1972 and spent the
next six years studying structural integration under Rolfing
founder Ida P. Rolf. He became the first president of the
Rolf Institute in 1975. During his training with Rolf, Heller
began developing his own system of bodywork. He left the
institute in 1978 and moved to Northern California where
he founded Hellerwork. He conducts classes and continues his work today at his headquarters, 406 Berry St.,
Mt. Shasta, CA 96067.

Hellerwork practitioners also teach better patterns
of movement for activities that are specific to each
individual, such as their job and favorite sports or
social activities.
Verbal dialogue
Verbal dialogue is the third aspect of Hellerwork.
It is designed to teach awareness of the relationships
among emotions, life attitudes, and the body.
Hellerwork practitioners believe that as patients
become responsible for their attitudes, their body
movements and patterns of self-expression improve.
Dialogue focuses on the theme of each session and
the area of the body that is worked on during that
session.
Hellerwork consists of eleven 90-minute sessions
costing about $90–100 each. The first three sessions
focus on the surface layers of the fascia and on developmental issues of infancy and childhood. The next
four sessions are the core sessions and work on the
deep layers and on adolescent developmental issues.
The final four treatments are the integrative sessions,
and build upon all the previous ones, while also looking at questions of maturity.
1741

Hellerwork

J O S E P H H E L L E R (1940– )

Hematocrit

Side effects

KEY TERMS
Bioenergetics—A system of therapy that combines breathing and body exercises, psychological therapy, and the free expression of
emotions to release blocked physical and psychic energy.
Bodywork—A term that covers a variety of therapies that include massage, realignment of the body,
and similar techniques to treat deeply ingrained
stresses and traumas carried in the tissues of the
body.
Chronic—A disease or condition that progresses
slowly but persists or reoccurs over time.
Fascia—The sheet of connective tissue that covers
the body under the skin and envelops the muscles
and various organs.
Gestalt therapy—A form of therapy that focuses on
helping patients reconnect with their bodies and
their feelings directly, as contrasted with verbal
intellectual analysis.
Kinesiology—The study of the anatomy and physiology of body movement, particularly in relation
to therapy.
Rolfing—A deep-tissue therapy that involves
manipulating the body’s fascia to realign and balance the body’s structure.

There are no reported serious side effects associated with Hellerwork when delivered by a certified
practitioner to adults and juveniles.

Research and general acceptance
As most alternative or holistic treatments, there is
little mainstream scientific research documenting the
effectiveness of Hellerwork therapy. Since the deep
tissue massage aspect of Hellerwork is similar to
Rolfing, however, several scientific studies of Rolfing
may be useful in evaluating Hellerwork. A 1988 study
published in the Journal of the American Physical
Therapy Association indicated that Rolfing stimulates
the parasympathetic nervous system, which can help
speed the recovery of damaged tissue. A 1997 article in
The Journal of Orthopaedic and Sports Physical
Therapy reported that Rolfing can provide effective
and sustained pain relief from lower back problems.
Resources
BOOKS

Golten, Roger. The Owner’s Guide to the Body. London:
Thorsons, 1999.
Levine, Andrew S., and Valerie J. Levine. The Bodywork and
Massage Sourcebook. Lincolnwood, IL: Lowell House,
1999.
ORGANIZATIONS

Hellerwork. 406 Berry St. Mt. Shasta, CA 96067.
(530) 926-2500. <http://www.hellerwork.com>.

Ken R. Wells

Preparations
No advance preparations are required to begin
Hellerwork treatment. The treatment is usually done
on a massage table with the patient wearing only
undergarments.

HELLP syndrome see Preeclampsia and
eclampsia
Hemangiomas see Birthmarks

Precautions
Since Hellerwork involves vigorous deep tissue
massage, it is often described as uncomfortable and
sometimes painful, especially during the first several
sessions. As it requires the use of hands, it may be a
problem for people who do not like or are afraid of
being touched. It is not recommended as a treatment
for any disease or a chronic inflammatory condition
such as arthritis, and can worsen such a condition.
Anyone with a serious medical condition, including
heart disease, diabetes, or respiratory problems,
should consult a medical practitioner before undergoing Hellerwork.
1742

Hematocrit
Definition
The hematocrit measures how much space in the
blood is occupied by red blood cells. It is useful when
evaluating a person for anemia.

Purpose
Blood is made up of red and white blood cells, and
plasma. A decrease in the number or size of red cells
GALE ENCYCLOPEDIA OF MEDICINE

The hematocrit is usually done on a person with
symptoms of anemia. An anemic person has fewer or
smaller than normal red cells. A low hematocrit, combined with other abnormal blood tests, confirms the
diagnosis.
Some conditions, such as polycythemia, cause an
overproduction of red blood cells, resulting in an
increased hematocrit.
Transfusion decisions are based on the results of
laboratory tests, including hematocrit. Transfusion is
not considered if the hematocrit level is reasonable.
The level differs for each person, depending on his or
her clinical condition.

Description

KEY TERMS
Anemia—A condition where a person has fewer or
smaller than normal red blood cells.
Hemoglobin—The percentage of space in blood
occupied by red blood cells.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure
to the puncture site until the bleeding stops reduces
bruising. Warm packs to the puncture site relieve
discomfort.

Normal results
Normal values vary with age and sex. Adult male
range is 42–52%, adult female 36–48%.

Abnormal results

Blood drawn from a fingerstick is often used for
hematocrit testing. The blood fills a small tube, which is
then spun in a small centrifuge. As the tube spins, the red
blood cells go to the bottom of the tube, the white blood
cells cover the red in a thin layer called the buffy coat, and
the liquid plasma rises to the top. The spun tube is examined for the line that divides the red cells from the buffy
coat and plasma. The height of the red cell column is
measured as a percent of the total blood column. The
higher the column of red cells, the higher the hematocrit.

Hematocrit values decrease when the size or number of red cells decrease. This is most common in
anemia, but other conditions have similar effects:
excessive bleeding, damaged cells due to a mechanical
heart valve, liver disease, and cancers affecting the
bone marrow. Additional tests, and the person’s
symptoms and medical history help distinguish these
conditions or diagnose a specific type of anemia.
Hematocrit values increase when the size or number
of red cells increase, such as in polycythemia.

The hematocrit test can also be done on an automated instrument as part of a complete blood count.
It is also called Packed Red Cell Volume or Packed
Cell Volume, or abbreviated as Hct or Crit. The test
is covered by insurance when medically necessary.
Results are usually available the same or following day.

Fluid volume in the blood affects the hematocrit.
Pregnant women have extra fluid, which dilutes the
blood, decreasing the hematocrit. Dehydration concentrates the blood, increasing the hematocrit.

Preparation

Nancy J. Nordenson

Hemiplegia see Paralysis

To collect the blood by fingerstick, a healthcare
worker punctures a finger with a lancet and allows the
blood to fill a small tube held to the puncture site.
Tests done on an automated instrument require
5–7 mL of blood. A healthcare worker ties a tourniquet on the person’s upper arm, locates a vein in the
inner elbow region, and inserts a needle into that vein.
Vacuum action draws the blood through the needle
into an attached tube. Collection of the sample takes
only a few minutes.
GALE ENCYCLOPEDIA OF MEDICINE

Hemochromatosis
Definition
Hemochromatosis is an inherited blood disorder
that causes the body to retain excessive amounts of
iron. This iron overload can lead to serious health
consequences, most notably cirrhosis of the liver.
1743

Hemochromatosis

also decreases the amount of space they occupy,
resulting in a lower hematocrit. An increase in the
number or size of red cells increases the amount of
space they occupy, resulting in a higher hematocrit.
Thalassemia is a condition which can cause an
increased number of red blood cells but a decreased
size and hematocrit.

Hemochromatosis

Description
Hemochromatosis is also known as iron overload,
bronze diabetes, hereditary hemochromatosis and
familial hemochromatosis. The inherited disorder
causes increased absorption of intestinal iron, well
beyond that needed to replace the body’s loss
of iron. Iron overload diseases afflict as many as
1.5 million persons in the United States. The most
common of these, as well as one of the most common genetic disorders in the United States, is hereditary hemochromatosis. Men and women are
equally affected by hemochromatosis, but women
are diagnosed later in life because of blood loss
from menstruation and childbirth. It most commonly appears in patients between the ages of 40–
60 years, since it takes many years for the body to
accumulate excessive iron. Symptoms appear later
in females than in males—usually after menopause.
Hemochromatosis causes excess iron storage
in several organs of the body including the liver,
pancreas, endocrine glands, heart, skin, joints, and
intestinal lining. The buildup of iron in these organs
can lead to serious complications, including heart failure, liver cancer, and cirrhosis of the liver. It is estimated that about 5% of cirrhosis cases are caused
by hereditary hemochromatosis.
Idiopathic pulmonary hemosiderosis, a disorder
afflicting children and young adults, is a similar
overload disorder characterized by abnormal accumulation of hemosiderin. Hemosiderin is a protein
found in most tissues, especially the liver. It is produced by digestion of hematin, an iron-related
substance.
Hemochromatosis is one of the most common
genetic disorders in the United States. Approximately
one in nine individuals have one abnormal hemochromatosis gene (11% of the population). Since everyone
has two copies of each gene, these individuals have
an abnormal HFE gene and a normal gene. They are
called carriers. Between 1/200–1/400 individuals have
two abnormal genes for hemochromatosis and no
normal gene.
With most autosomal recessive conditions, an
affected person’s parents are carriers. If more than
one family member has the condition, they are siblings. Hemochromatosis is so common, however, that
families are seen in which both parents are affected,
or one parent is affected and the other parent is a
carrier. More than one generation may be affected,
which is not usually seen in rare autosomal recessive
conditions.
1744

Causes and symptoms
Hereditary hemochromatosis is an autosomal
recessive condition. This means that individuals with
hemochromatosis have inherited an altered (mutated)
gene from both of their parents. Affected individuals
have two abnormal hemochromatosis genes and
no normal hemochromatosis gene.
The gene that causes hemochromatosis has been
identified, and the most common abnormalities of the
gene have been described. The gene is on chromosome
6; it is called HFE. Scientists have not confirmed the
function of the normal gene product; they do know
that it interacts with the cell receptor for transferrin.
Transferrin binds and transports iron in the blood.
Because it is an autosomal recessive condition,
siblings of individuals who have hemochromatosis
are at a 25% risk to also be affected. However, the
likelihood that an individual will develop symptoms
depends on which gene mutation he or she has as well
as environmental factors. The two most common
changes in the HFE gene are C282Y and H63D. The
age at which symptoms begin is variable, even within
the same family.
The symptoms of hemochromatosis include fatigue, weight loss, weakness, shortness of breath, heart
palpitations, chronic abdominal pain, and impaired
sexual performance. The patient may also show symptoms commonly connected with heart failure, diabetes
or cirrhosis of the liver. Changes in the pigment of the
skin may appear, such as grayness in certain areas, or a
tanned or yellow (jaundice) appearance. The age of
onset and initial symptoms vary.
Idiopathic pulmonary hemosiderosis may first,
and only, appear as paleness of the skin. Sometimes,
the patient will experience spitting of blood from the
lungs or bronchial tubes.

Diagnosis
The most common diagnostic methods for hemochromatosis are blood studies of iron, genetic blood
studies, magnetic resonance imaging (MRI), and liver
biopsy. Blood studies of transferrin–iron saturation
and ferritin concentration are often used to screen
for iron overload. Ferritin is a protein that transports
iron and liver enzymes. Additional studies are performed to confirm the diagnosis.
Blood studies used to confirm the diagnosis
include additional iron studies and/or genetic blood
studies. Genetic blood studies became available in the
late 1990s. Genetic testing is a reliable method of diagnosis. However, in the year 2001 scientists and
GALE ENCYCLOPEDIA OF MEDICINE

MRI scans and/or liver biopsy may be necessary
to confirm the diagnosis. MRI studies of the liver (or
other iron absorbing organs), with quantitative assessment of iron concentration, may reveal abnormal iron
deposits. For the liver biopsy, a thin needle is inserted
into the liver while the patient is under local anesthesia.
The needle will extract a small amount of liver tissue,
which can be analyzed microscopically to measure its
iron content and other signs of hemochromatosis.
Diagnosis of idiopathic pulmonary hemosiderosis
begins with blood tests and x-ray studies of the chest.

Treatment
Patients who show signs of iron overload will
often be treated with phlebotomy. Phlebotomy is a
procedure that involves drawing blood from the
patient, just like blood donation. Its purpose as a treatment is to rid the body of excess iron storage. Patients
may need these procedures one or two times a week for
a year or more. Less frequent phlebotomy may be
continued in subsequent years to keep excess iron
from accumulating. Patients who cannot tolerate phlebotomy due to other medical problems can be treated
with Desferal (desferrioxamine). Diet restrictions may
also be prescribed to limit the amount of iron ingested.
Complications from hemochromatosis, such as cirrhosis or diabetes, may also require treatment. Treatment
for idiopathic pulmonary hemosiderosis is based on
symptoms.
Diet restrictions may help lower the amount of
iron in the body, but do not prevent or treat hemochromatosis. Individuals who are affected or who
know they have two C282Y and/or H63D genes may
reduce iron intake by avoiding iron and mineral supplements, excess vitamin C, and uncooked seafood. If
a patient is symptomatic, he/she may be advised to
abstain from drinking alcohol.

Prognosis
With early detection and treatment, the prognosis
is usually good. All potential symptoms are prevented
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Autosomal—Relating to any chromosome besides
the X and Y sex chromosomes. Human cells contain 22 pairs of autosomes and one pair of sex
chromosomes.
Cirrhosis—A chronic degenerative disease of the
liver, in which normal cells are replaced by fibrous
tissue. Cirrhosis is a major risk factor for the later
development of liver cancer.
Diabetes mellitus—The clinical name for common
diabetes. It is a chronic disease characterized by
inadequate production or use of insulin.
Phlebotomy—The taking of blood from the body
through an incision in the vein, usually in the treatment of disease.

if iron levels are kept within the normal range, which
is possible if the diagnosis is made before an individual
is symptomatic. If a patient is symptomatic but
treated successfully before he/she develops liver cirrhosis, the patient’s life expectancy is near normal.
However, if left untreated, complications may arise
which can be fatal. These include liver cancer, liver
cirrhosis, diabetes mellitus, congestive heart failure,
and difficulty depleting iron overload through phlebotomy. Liver biopsy can be helpful in determining
prognosis of more severely affected individuals.
Genetic testing may also be helpful, as variable severity
has been noted in patients who have two C282Y genes
compared to patients with two H63D genes or one of
each. Men are two times more likely than women to
develop severe complications. The prognosis for
patients with idiopathic pulmonary hemosiderosis is
fair, depending on detection and complications.

Prevention
Screening for hemochromatosis is cost effective,
particularly for certain groups of people. Relatives of
patients with hemochromatosis—including children,
siblings, and parents—should be tested by the most
appropriate method. The best screening method may
be iron and ferritin studies or genetic testing. If the
affected person’s diagnosis has been confirmed
by genetic testing, relatives may have genetic testing
to determine whether or not they have the genetic
changes present in the affected individual. Many
medical groups oppose genetic testing of children.
Relatives who are affected but do not have symptoms
can reduce iron intake and/or begin phlebotomy prior
1745

Hemochromatosis

physicians are studying how accurately having a
hemochromatosis mutation predicts whether a person
will develop symptoms. Most individuals affected with
hemochromatosis (87%) have two identifiable gene
mutations; that is, genetic testing will confirm the diagnosis in most individuals. Genetic studies are also be
used to determine whether the affected person’s family
members are at risk for hemochromatosis. The results
of genetic testing are the same whether or not a person
has developed symptoms.

Hemoglobin electrophoresis

to the onset of symptoms, possibly preventing ever
becoming symptomatic.
In the winter of 2000, population screening for
hereditary hemochromatosis is being widely debated.
Many doctors and scientists want population screening because hemochromatosis is easily and cheaply
treated, and quite common. Arguments against treatment include the range of symptoms seen (and not
seen) with certain gene mutations, and the risk of
discrimination in health and life insurance. Whether
or not population screening becomes favored by a
majority, the publicity is beneficial. Hemochromatisis
is a common, easily and effectively treated condition.
However, diagnosis may be difficult because the presenting symptoms are the same as those seen with
many other medical problems. The screening debate
has the positive effect of increasing awareness and
suspicion of hemochromatisis. Increased knowledge
leads to earlier diagnosis and treatment of symptomatic individuals, and increased testing of their
asymptomatic at-risk relatives.
Resources
BOOKS

Barton, James C., and Corwin Q. Edwards, editors.
Hemochromatosis: Genetics, Pathophysiology,
Diagnosis and Treatment. Cambridge: Cambridge
University Press, 2000.
PERIODICALS

Motulsky, A.G., and E. Beutler. ‘‘Population Screening for
Hemochromatosis.’’ Annual Review of Public Health 21
(2000): 65-79.
ORGANIZATIONS

American Hemochromatosis Society, Inc. 777 E. Atlantic
Ave., PMB Z-363, Delray Beach, FL 33483-5352. (561)
266-9037 or (888) 655-IRON (4766). ahs@emi.net.
<http://www.americanhs.org>.
American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
Hemochromatosis Foundation, Inc. PO Box 8569, Albany,
NY 12208-0569. (518) 489-0972. s.kleiner@shiva.
hunter.cuny.edu. <http://
www.hemochromatosis.org>.
Iron Disorders Institute, Inc. PO Box 3021, Greenville, SC
29602. (864) 241-0111. irondis@aol.com. <http://
www.irondisorders.org>.
Iron Overload Diseases Association, Inc. 433 Westwind Dr.,
North Palm Beach, FL 33408. (561) 840-8512.
iod@ironoverload.org.
OTHER

‘‘Hemochromatosis.’’ GeneClinics. <http://www.geneclinics.
org/profiles/hemochromatosis/>.
1746

Hemochromatosis Information Sheet. National Institute of
Diabetes & Digestive & Kidney Diseases (NIDDK).
<http://www.niddk.nih.gov/health/digest/pubs/
hemochrom/hemochromatosis.htm>.
Hereditary Hemochromatosis. Lecture by Richard Fass,
MD, hematologist, Advanced Oncology Associates, given
April 25, 1999. <http://www.advancedoncology.org/
listen.htm>.

Michelle Q. Bosworth, MS, CGC

Hemodialysis see Dialysis, kidney

Hemoglobin electrophoresis
Definition
Hemoglobin electrophoresis (also called Hgb electrophoresis), is a test that measures the different types of
hemoglobin in the blood. The method used is called
electrophoresis, a process that causes movement of particles in an electric field, resulting in formation of ‘‘bands’’
that separate toward one end or the other in the field.

Purpose
Hgb electrophoresis is performed when a disorder
associated with abnormal hemoglobin (hemoglobinopathy) is suspected. The test is used primarily to
diagnose diseases involving these abnormal forms
of hemoglobin, such as sickle cell anemia and
thalassemia.

Precautions
Blood transfusions within the previous 12 weeks
may alter test results.

Description
Hemoglobin (Hgb) is comprised of many different
types, the most common being A1, A2, F, S, and C.
Hgb A1 is the major component of hemoglobin
in the normal red blood cell. Hgb A2 is a minor
component of normal hemoglobin, comprising
approximately 2–3% of the total.
Hgb F is the major hemoglobin component in
the fetus, but usually exists only in minimal quantities
in the normal adult. Levels of Hgb F greater than 2%
in patients over three years of age are considered
abnormal.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Hemoglobin C disease—A disease of abnormal
hemoglobin, occurring in 2–3% of AfricanAmericans. Only those who have two genes for
the disease develop anemia, which varies in severity. Symptoms include episodes of abdominal and
joint pain, an enlarged spleen and mild jaundice.

Hgb C is another hemoglobin variant found in
African Americans. Red blood cells containing Hgb
C have a decreased life span and are more readily
destroyed than normal red blood cells, resulting in
mild to severe hemolytic anemia.

Hemoglobin H disease—A thalassemia-like syndrome causing moderate anemia and red blood
cell abnormalities.
Heterozygous—Two different genes controlling a
specified inherited trait.

Each of the major hemoglobin types has an electrical charge of a different degree, so the most useful
method for separating and measuring normal and
abnormal hemoglobins is electrophoresis. This process
involves subjecting hemoglobin components from
dissolved red blood cells to an electric field. The components then move away from each other at different
rates, and when separated form a series of distinctly
pigmented bands. The bands are then compared with
those of a normal sample. Each band can be further
assessed as a percentage of the total hemoglobin, thus
indicating the severity of any abnormality.

Homozygous—Identical genes controlling a specified inherited trait.
Thalassemias—The name for a group of inherited
disorders resulting from an imbalance in the production of one of the four chains of amino acids that
make up hemoglobin. Thalassemias are categorized
according to the amino acid chain affected. The
two main types are alpha-thalassemia and betathalassemia. The disorders are further characterized
by the presence of one defective gene (thalassemia
minor) or two defective genes (thalassemia major).
Symptoms vary, but include anemia, jaundice, skin
ulcers, gallstones, and an enlarged spleen.

Preparation
This test requires a blood sample. No special preparation is needed before the test.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting
or feeling lightheaded after venipuncture, or hematoma (blood accumulating under the puncture site).

Abnormal results
Abnormal reference values can vary by laboratory, but when they appear within these ranges, results
are usually associated with the conditions that follow
in parentheses.

Normal results
Normal reference values can vary by laboratory,
but are generally within the following ranges.
Adults:

Hgb A2:


4–5.8% ( -thalassemia minor)



under 2% (Hgb H disease)
Hgb F:



Hgb A1: 95–98%



Hgb A2: 2–3%



2–5% ( -thalassemia minor)



Hgb F: 0.8–2.0%



10–90% ( -thalassemia major)



Hgb S: 0%





Hgb C: 0%.

5–35% (Heterozygous hereditary persistence of fetal
hemoglobin, or HPFH)



100% (Homozygous HPFH)



15% (Homozygous Hgb S)

Child (Hgb F):


6 months: 8%



greater than 6 months: 1–2%



newborn (Hgb F): 50–80%

GALE ENCYCLOPEDIA OF MEDICINE

Homozygous Hgb S:


70–98% (Sickle cell disease).
1747

Hemoglobin electrophoresis

Hgb S is an abnormal form of hemoglobin associated with the disease of sickle cell anemia, which
occurs predominantly in African-Americans. A distinguishing characteristic of sickle cell disease is the crescent-shaped red blood cell. Because the survival rate of
this type of cell is limited, patients with sickle cell
disease also have anemia.

Hemoglobin test

Description

Homozygous Hgb C:


90–98% (Hgb C disease)

Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Hemoglobin F test see Fetal hemoglobin test

Hemoglobin test
Definition
Hemoglobin is a protein inside red blood cells that
carries oxygen throughout the body. A hemoglobin
test reveals how much hemoglobin is in a person’s
blood, helping to diagnose and monitor anemia and
polycythemia vera.

Purpose
A hemoglobin test is done when a person is ill
or during a general physical examination. Good
health requires an adequate amount of hemoglobin.
The amount of oxygen in the body tissues depends
on how much hemoglobin is in the red cells. Without
enough hemoglobin, the tissues lack oxygen and
the heart and lungs must work harder to try to
compensate.
If the test indicates a ‘‘less than’’ or ‘‘greater than’’
normal amount of hemoglobin, the cause of the
decrease or increase must be discovered. A low hemoglobin usually means the person has anemia. Anemia
results from conditions that decrease the number or
size of red cells, such as excessive bleeding, a dietary
deficiency, destruction of cells because of a transfusion
reaction or mechanical heart valve, or an abnormally
formed hemoglobin.
A high hemoglobin may be caused by polycythemia vera, a disease in which too many red blood cells
are made.
Hemoglobin levels also help determine if a person
needs a blood transfusion. Usually a person’s hemoglobin must be below 8 gm/dl before a transfusion is
considered.
1748

Hemoglobin is made of heme, an iron compound,
and globin, a protein. The iron gives blood its red
color. Hemoglobin tests make use of this red color.
A chemical is added to a sample of blood to make the
red blood cells burst. When they burst, the red cells
release hemoglobin into the surrounding fluid, coloring it clear red. By measuring the color using an instrument called a spectrophotometer, the amount of
hemoglobin is determined.
Hemoglobin is often ordered as part of a complete
blood count (CBC), a test that includes other blood
cell measurements.
Some people inherit hemoglobin with an abnormal structure. These abnormal hemoglobins cause
diseases, such as sickle cell or Hemoglobin C disease.
Special tests, using a process called hemoglobin
electrophoresis, identify abnormal hemoglobins.

Preparation
This test requires 5 mL of blood. A healthcare
worker ties a tourniquet on the person’s upper arm,
locates a vein in the inner elbow region, and inserts a
needle into that vein. Vacuum action draws the blood
through the needle into an attached tube. Collection
of the sample takes only a few minutes.
The person should avoid smoking before this test
as smoking can increase hemoglobin levels.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure
to the puncture site until the bleeding stops reduces
bruising. Warm packs to the puncture site relieve
discomfort.

Normal results
Normal values vary with age and sex. Women
generally have lower hemoglobin values than men.
Men have 14.0–18.0 g/dL, while women have levels
of 12.0–16.0 g/dL.

Abnormal results
A low hemoglobin usually indicates the person
has anemia. Further tests are done to discover the
cause and type of anemia. Dangerously low hemoglobin levels put a person at risk of a heart attack,
congestive heart failure, or stroke.
GALE ENCYCLOPEDIA OF MEDICINE

Anemia—A condition characterized by a decrease
in the size or number of red blood cells.
Hemoglobin—A protein inside red blood cells that
carries oxygen to body tissues.
Polycythemia vera—A disease in which the bone
marrow makes too many red blood cells.

A high hemoglobin indicates the body is making
too many red cells. Further tests are done to see if this
is caused by polycythemia vera, or as a reaction to
illness, high altitudes, heart failure, or lung disease.
Fluid volume in the blood affects hemoglobin
values. Pregnant women and people with cirrhosis
have extra fluid, which dilutes the blood, decreasing
the hemoglobin. Dehydration concentrates the blood,
increasing the hemoglobin.
Resources
PERIODICALS

Hsia, Connie C. W. ‘‘Respiratory Function of
Hemoglobin.’’New England Journal of Medicine 338
(January 1998): 239-247.

Nancy J. Nordenson

Hemoglobinopathies
Definition
Hemoglobinopathies are genetic (inherited) disorders of hemoglobin, the oxygen-carrying protein of
the red blood cells.

Description
The hemoglobin molecule is composed of four
separate polypeptide chains of amino acids, two
alpha chains and two beta chains, as well as four
iron-bearing heme groups that bind oxygen. The
alpha chains are coded for by two similar genes on
chromosome 16; the beta chains by a single gene on
chromosome 11. Mutations and deletions in these
genes cause one of the many hemoglobinopathies.
In general, hemoglobinopathies are divided into
those in which the gene abnormality results in a
GALE ENCYCLOPEDIA OF MEDICINE

qualitative change in the hemoglobin molecule and
those in which the change is quantitative. Sickle cell
anemia (sickle cell disease) is the prime example of
the former, and the group of disorders known as the
thalassemias constitute the latter. It has been estimated that one third of a million people worldwide
are seriously affected by one of these genetic disorders.

Causes and symptoms
Sickle cell anemia (SSA), an autosomal recessive
disorder more common in the Black population, is
caused by a single mutation in the gene that codes
for the beta polypeptide. Approximately 1/400 to
1/600 African-Americans are born with the disorder,
and, one in ten is a carrier of one copy of the mutation.
In certain parts of the African continent, the prevalence of the disease reaches one in fifty individuals.
The sickle cell mutation results in the substitution
of the amino acid valine for glutamic acid in the sixth
position of the beta polypeptide. In turn, this alters the
conformation of the hemoglobin molecule and causes
the red blood cells to assume a characteristic sickle
shape under certain conditions. These sickle-shaped
cells, no longer able to pass smoothly through small
capillaries, can block the flow of blood. This obstruction results in symptoms including growth retardation, severe pain crises, tissue and organ damage,
splenomegaly, and strokes. Individuals with SSA are
anemic and prone to infections, particularly pneumonia, a significant cause of death in this group. Some
or all of these symptoms are found in individuals
who have the sickle mutation in both copies of their
beta-globin gene. Persons with one abnormal gene and
one normal gene are said to be carriers of the sickle
cell trait. Carriers are unaffected because of the
remaining normal copy of the gene.
The thalassemias are a diverse group of disorders
characterized by the fact that the causative mutations
result in a decrease in the amount of normal hemoglobin. Thalassemias are common in Mediterranean
populations as well as in Africa, India, the Mideast,
and Southeast Asia. The two main types of thalassemias are alpha-thalassemia due to mutations in the
alpha polypeptide and beta-thalassemia resulting
from beta chain mutations.
Since individuals possess a total of four genes for
the alpha polypeptide (two genes on each of their two
chromosomes 16), disease severity depends on how
many of the four genes are abnormal. A defect in one
or two of the genes has no clinical effect. Abnormalities
of three results in a mild to moderately severe anemia
(hemoglobin H disease) and splenomegaly. Loss of
1749

Hemoglobinopathies

KEY TERMS

Hemoglobinopathies

function of all four genes usually causes such severe
oxygen deprivation that the affected fetus does not
survive. A massive accumulation of fluid in the fetus
(hydrops fetalis) results in stillbirth or neonatal death.
Beta thalassemias can range from mild and clinically insignificant (beta thalassemia minor) to severe
and life-threatening (beta thalassemia major, also
known as Cooley’s anemia), depending on the exact
nature of the gene mutation and whether one or both
copies of the beta gene are affected. While the milder
forms may only cause slight anemia, the more severe
types result in growth retardation, skeletal changes,
splenomegaly, vulnerability to infections, and death as
early as the first decade of life.

Diagnosis
Many countries, including the United States, have
made concerted efforts to screen for sickle cell anemia
at birth because of the potential for beginning early
treatment and counseling parents about their carrier
status. Diagnosis is traditionally made by blood tests
including hemoglobin electrophoresis. Similar tests are
used to determine whether an individual is a sickle cell
or thalassemia carrier. In certain populations with a
high prevalence of one of the mutations, carrier testing
is common. If both members of a couple are carriers
of one of these conditions, it is possible through prenatal genetic testing to determine if the fetus will be
affected, although the severity of the disease cannot
always be predicted.

Treatment
Treatment of SSA has improved greatly in recent
years with a resulting increase in life expectancy. The
use of prophylactic (preventative) antibiotic therapy
has been particularly successful. Other treatments
include fluid therapy to prevent dehydration, oxygen
supplementation, pain relievers, blood transfusions,
and several different types of medications. Recent
interest has focused on bone marrow transplantation,
which has been successful in selected patients.
Since the clinically important thalassemias are
characterized by severe anemia, the traditional treatment has been blood transfusion, but the multiple
transfusions needed to sustain life lead to an iron
overload throughout the tissues of the body and eventual destruction of the heart and other organs. For
this reason, transfusion therapy must also include
infusions of medications such as deferoxamine (desferroxamine) to rid the body of excess iron. Phlebotomy
is another technique that has been used with some
1750

success to lower the concentration of iron in the
patient’s blood. As with sickle cell anemia, bone marrow therapy has been successful in some cases.
Until very recently, patients being treated with
bone marrow transplants had to find a sibling or
other closely related donor in order to avoid rejection
of the transplant. Advances in the preparation of the
transplanted cells, however, have made the use of bone
marrow from unrelated donors (URD) an option for
patients with hemoglobinopathies. As of 2003, the
National Marrow Donor Program reports that about
40% of bone marrow transplants involve a patient
in the United States receiving marrow from an international donor or an international patient receiving
marrow from a donor in the United States.
Emphasis is also being placed on developing drugs
that treat sickle cell anemia directly. The most promising of these drugs in the late 1990s is hydroxyurea, a
drug that was originally designed for anticancer treatment. Hydroxyurea has been shown to reduce the
frequency of painful crises and acute chest syndrome
in adults, and to lessen the need for blood transfusions. Hydroxyurea seems to work by inducing a
higher production of fetal hemoglobin. The major
side effects of the drug include decreased production
of platelets, red blood cells, and certain white blood
cells. The effects of long-term hydroxyurea treatment
are unknown; however, a nine-year follow-up study of
299 adults with frequent painful crises reported in
2003 that taking hydroxyurea was associated with a
40% reduction in mortality.
Another promising development for the treatment
of hemoglobinopathies is gene therapy, which has
interested researchers since the early 1990s. In late
2001, genetic scientists reported that they had
designed a gene that might lead to a future treatment
of sickle cell anemia. Although the gene had not been
tested in humans, early results showed that the injected
gene protected cells from sickling. As of 2003, experiments in gene therapy for sickle cell disease have been
carried out in mice, using lentiviral vectors to transfer
the corrective gene into the mouse’s stem cells. This
technique, however, has not yet been attempted in
human subjects as of late 2003.

Prognosis
Hemoglobinopathies are life-long disorders.
The prognosis depends upon the exact nature of
the mutation, the availability of effective treatment,
as well as the individual’s compliance with therapies.
Hemoglobinopathies significantly complicate pregnancy, and increase the risk of infant mortality.
GALE ENCYCLOPEDIA OF MEDICINE

Amino acids—Organic compounds that form the
building blocks of protein. There are 20 different
amino acids.
Autosomal recessive—A pattern of inheritance in
which both copies of an autosomal gene must be
abnormal for a genetic condition or disease to
occur. An autosomal gene is a gene that is located
on one of the autosomes or non-sex chromosomes.
When both parents have one abnormal copy of
the same gene, they have a 25% chance with
each pregnancy that their offspring will have the
disorder.
Hemoglobin—Protein-iron compound in the blood
that carries oxygen to the cells and carries carbon
dioxide away from the cells.
Hydroxyurea—A drug that has been shown to
induce production of fetal hemoglobin. Fetal
hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of
adult hemoglobin. Higher-than-normal levels of
fetal hemoglobin can prevent sickling from
occurring.
Phlebotomy—Drawing blood from a vein for diagnosis or treatment. Phlebotomy is sometimes used
in the treatment of hemoglobinopathies to lower
the iron concentration of the blood.
Sickle cell—A red blood cell that has assumed
an elongated shape due to the presence of hemoglobin S.
Splenomegaly—Enlargement of the spleen.

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Pregnancy Complicated by Disease:
Hemoglobinopathies.’’ Section 18, Chapter 251 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Behrman, Richard E., et al.Nelson Textbook of Pediatrics.
16th ed. Philadelphia, W. B. Saunders, 2000.
Jorde, Lynn B., et al. Medical Genetics. 2nd ed. New York:
Mosby, 1999.
PERIODICALS

Davies, S. C., and A. Gilmore. ‘‘The Role of Hydroxyurea in
the Management of Sickle Cell Disease.’’ Blood Reviews
17 (June 2003): 99–109.
Koduri, P. R. ‘‘Iron in Sickle Cell Disease: A Review Why
Less Is Better.’’ American Journal of Hematology 73
(May 2003): 59–63.
Krishnamurti, L., S. Abel, M. Maiers, and S. Flesch.
‘‘Availability of Unrelated Donors for Hematopoietic
Stem Cell Transplantation for Hemoglobinopathies.’’
Bone Marrow Transplantation 31 (April 2003):
547–550.
Markham, M. J., R. Lottenberg, and M. Zumberg. ‘‘Role
of Phlebotomy in the Management of Hemoglobin SC
Disease: Case Report and Review of the Literature.’’
American Journal of Hematology 73 (June 2003):
121–125.
Nienhuis, A. W., H. Hanawa, N. Sawai, et al. ‘‘Development
of Gene Therapy for Hemoglobin Disorders.’’ Annals
of the New York Academy of Science 996 (May 2003):
101–111.
Olivieri, Nancy F. ‘‘The Beta-Thalassemias.’’ The New
England Journal of Medicine 341, no. 2 (July 1999):
99–109.
Steinberg, M. H., F. Barton, O. Castro, et al. ‘‘Effect of
Hydroxyurea on Mortality and Morbidity in Adult
Sickle Cell Anemia: Risks and Benefits up to 9 Years
of Treatment.’’ Journal of the American Medical
Association 289 (April 2, 2003): 1645–1651.
ORGANIZATIONS

Prevention
Because the hemoglobinopathies are inherited diseases, primary prevention involves carriers making
reproductive decisions to prevent passage of the
abnormal gene to their offspring. At present, most
prevention is targeted toward the symptoms using
treatments such as those described above.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Anemias Caused by Excessive Hemolysis: Sickle Cell
Diseases.’’ Section 11, Chapter 127 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
GALE ENCYCLOPEDIA OF MEDICINE

American Sickle Cell Anemia Association. <http://
www.ascaa.org>.
National Marrow Donor Program (NMDP). Suite 500,
3001 Broadway Street Northeast, Minneapolis, MN
55413. (800) 627-7692. <http://www.marrowdonor.org>.
Sickle Cell Disease Association of America, Inc. 200
Corporate Point Suite 495, Culver City, CA 902308727. (800) 421-8453. Scdaa@sicklecelldisease.org.
<http://sicklecelldisease.org/>.
Sickle Cell Information Center. PO Box 109, Grady
Memorial Hospital, 80 Bulter Street, SE, Atlanta,
GA 30303. (404) 616- 3572. <http://
www.emory.edu>.

Sallie Boineau Freeman, PhD
Rebecca J. Frey, PhD
1751

Hemoglobinopathies

KEY TERMS

Hemolytic anemia

Hemolytic anemia
Definition
Red blood cells have a normal life span of
approximately 90–120 days, at which time the old
cells are destroyed and replaced by the body’s natural
processes. Hemolytic anemia is a disorder in which the
red blood cells are destroyed prematurely. The cells
are broken down at a faster rate than the bone marrow
can produce new cells. Hemoglobin, the component of
red blood cells that carries oxygen, is released when
these cells are destroyed.

Description
As a group, anemias (conditions in which the
number of red blood cells or the amount of hemoglobin in them is below normal) are the most common
blood disorders. Hemolytic anemias, which result
from the increased destruction of red blood cells, are
less common than anemias caused by excessive blood
loss or by decreased hemoglobin or red cell production.
Since a number of factors can increase red blood
cell destruction, hemolytic anemias are generally identified by the disorder that brings about the premature
destruction. Those disorders are classified as either
inherited or acquired. Inherited hemolytic anemias
are caused by inborn defects in components of the
red blood cells—the cell membrane, the enzymes, or
the hemoglobin. Acquired hemolytic anemias are
those that result from various other causes. With this
type, red cells are produced normally, but are prematurely destroyed because of damage that occurs to
them in the circulation.

Causes and symptoms
Inherited hemolytic anemias involve conditions
that interfere with normal red blood cell production.
Disorders that affect the red blood cell membrane
include hereditary spherocytosis, in which the normally disk-shaped red cells become spherical, and
hereditary elliptocytosis, in which the cells are oval,
rather than disk-shaped. Other hereditary conditions
that cause hemolytic anemia include disorders of the
hemoglobin, such as sickle cell anemia and thalassemia,
and red blood cell enzyme deficiencies, such as G6PD
deficiency.
The causes of acquired hemolytic anemias vary,
but the most common are responses to certain medications and infections. Medications may cause the body
to develop antibodies that bind to the red blood cells
1752

and cause their destruction in the spleen. Immune
hemolytic anemia most commonly involves antibodies
that react against the red blood cells at body temperature (warm-antibody hemolytic anemia), which can
cause premature destruction of the cells. About 20%
of hemolytic anemias caused by warm antibodies
come from diseases such as lymphocytic leukemia,
10% from an autoimmune disease, and others are
drug-induced. Cold-antibody hemolytic anemia is a
condition in which the antibodies react with the red
blood cells at a temperature below that of normal
body temperature. Red blood cells can also receive
mechanical damage as they circulate through the
blood vessels. Aneurysms, artificial heart valves, or
very high blood pressure can cause the red cells to
break up and release their contents. In addition, hemolytic anemia may be caused by a condition called
hypersplenism, in which a large, overactive spleen
rapidly destroys red blood cells.
Major symptoms of hemolytic anemias are similar
to those for all anemias, including shortness of breath;
noticeable increase in heart rate, especially with exertion; fatigue; pale appearance; and dark urine. A yellow
tint, or jaundice, may be seen in the skin or eyes of
hemolytic anemia patients. Examination may also
show an enlarged spleen. A more emergent symptom
of hemolytic anemia is pain in the upper abdomen.
Severe anemia is indicated if there are signs of heart
failure or an enlarged liver.

Diagnosis
In order to differentiate hemolytic anemia from
others, physicians will examine the blood for the number of young red blood cells, since the number of
young cells is increased in hemolytic anemia. The physician will also examine the abdominal area to check
for spleen or liver enlargement. If the physician knows
the duration of hemolysis, it may also help differentiate between types of anemia. There are a number of
other indications that can be obtained from blood
samples that will help a physician screen for hemolytic
anemia. An antiglobulin (Coomb’s) test may be performed as the initial screening exam after determining
hemolysis. In the case of immune hemolytic anemia,
a direct Coomb’s test is almost always positive.

Treatment
Treatment will depend on the cause of the anemia, and may involve treatment of the underlying
cause. If the hemolytic anemia was brought on by
hereditary spherocytosis, the spleen may be removed.
Corticosteroid medications, or adrenal steroids, may
GALE ENCYCLOPEDIA OF MEDICINE

Hemolytic-uremic syndrome

Antibody—Antibodies are parts of the immune system which counteract or eliminate foreign substances or antigens.
Erythrocyte—The name for red blood cells or red
blood corpuscles. These components of the blood
are responsible for carrying oxygen to tissues and
removing carbon dioxide from tissues.
Hemolysis—The process of breaking down of red
blood cells. As the cells are destroyed, hemoglobin,
the component of red blood cells which carries the
oxygen, is liberated.
Thalassemia—One of a group of inherited blood
disorders characterized by a defect in the metabolism of hemoglobin, or the portion of the red blood
cells that transports oxygen throughout the blood
stream.

be effective, especially in hemolytic anemia due to
antibodies. If the cause of the disorder is a medication,
the medication should be stopped. When anemia is
severe in conditions such as sickle cell anemia and
thalassemia, blood transfusions may be indicated.

Prognosis
Hemolytic anemias are seldom fatal. However, if
left untreated, hemolytic anemia can lead to heart
failure or liver complications.

Prevention
Hemolytic anemia due to inherited disorders can
not be prevented. Acquired hemolytic anemia may be
prevented if the underlying disorder is managed
properly.
Resources
ORGANIZATIONS

American Autoimmune Related Diseases Association, Inc.
Focus: A quarterly newsletter of the AARDA. Detroit,
MI. (313) 371-8600. <http://www.aarda.org>.
The American Society of Hematology. 1200 19th Street NW,
Suite 300, Washington, DC 20036-2422. (202) 8571118. <http://www.hematology.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Teresa Odle
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Hemolytic-uremic syndrome (HUS) is a rare
condition that affects mostly children under the age
of 10, but also may affect the elderly as well as persons
with other illnesses. HUS, which most commonly
develops after a severe bowel infection with certain
toxic strains of a bacteria, is characterized by destruction of red blood cells, damage to the lining of blood
vessel walls, and in severe cases, kidney failure.

Description
Most cases of HUS occur after an infection in
the digestive system that has been caused by toxinproducing strains of the bacterium Escherichia coli.
About 75% of HUS cases in the United States are
caused by the strain referred to as E. coli O157:H7,
which is found in the intestinal tract of cattle, while the
remaining cases are caused by non-O157 strains. Some
children infected with E. coli O157:H7 will develop
HUS. HUS also can follow respiratory infection episodes in young children. In the United States, there
are about 20,000 infections and 250 deaths annually
that are caused by E. coli O157:H7. HUS has also been
known to occur in persons using drugs such as oral
contraceptives, immunosuppressors, and antineoplastics, and in women during the postpartum period.
E. coli. O157:H7, first identified in 1982, and isolated with increasing frequency since then, is found in
contaminated foods such as meat, dairy products, and
juices. Infection with E. coli. O157:H7 causes severe
gastroenteritis, which can include abdominal pain,
vomiting, and bloody diarrhea. For most children, the
vomiting and diarrhea stop within two to three days.
However, about 5 to 10% of the children will develop
HUS and will become pale, tired, and irritable. Toxins
produced by the bacteria enter the blood stream, where
they destroy red blood cells and platelets, which contribute to the clotting of blood. The damaged red blood
cells and platelets clog tiny blood vessels in the kidneys,
or form lesions to occur in the kidneys, making it
difficult for the kidneys to remove wastes and extra
fluid from the body, resulting in hypertension, fluid
accumulation, and reduced production of urine.

Causes and symptoms
The most common way an E. coli O157:H7 infection is contracted is through the consumption of
undercooked ground beef (e.g., eating hamburgers
1753

Hemolytic-uremic syndrome

KEY TERMS

Hemolytic-uremic syndrome

that are still pink inside). Healthy cattle carry E. coli
within their intestines. During the slaughtering process, the meat can become contaminated with the
E. coli from the intestines. When contaminated beef
is ground up, the E. coli are spread throughout the
meat. Additional ways to contract an E. coli infection
include drinking contaminated water and unpasteurized milk and juices, eating contaminated fruits and
vegetables, and working with cattle. The infection is
also easily transmitted from an infected person to
others in settings such as day care centers and nursing
homes when improper sanitary practices are used.
Symptoms of an E. coli O157:H7 infection start
about seven days after infection with the bacteria. The
first symptom is sudden onset of severe abdominal
cramps. After a few hours, watery diarrhea starts, causing loss of fluids and electrolytes (dehydration), which
causes the person to feel tired and ill. The watery
diarrhea lasts for about a day, and then changes to
bright red bloody stools, as the infection causes sores
to form in the intestines. The bloody diarrhea lasts for
two to five days, with as many as ten bowel movements
a day. Additional symptoms may include nausea and
vomiting, without a fever, or with only a mild fever.
After about five to ten days, HUS can develop, which is
characterized by paleness, irritability, and fatigue, as
well as reduced urine production.

Diagnosis
The diagnosis of an E. coli infection is made
through a stool culture. The culture must be taken
within the first 48 hours after the start of the bloody
diarrhea. If a positive culture is obtained, the patient
should be monitored for the development of HUS,
with treatment initiated as required.
Children should not go to day care until they have
had two negative stool cultures. Older people in nursing homes should stay in bed until two stool cultures
are negative.

Treatment
Treatment of HUS is supportive, with particular
attention to management of fluids and electrolytes.
Treatment generally is provided in a hospital setting.
Blood transfusions may be required. In about 50%
of the cases, short term replacement of kidney function
is required in the form of dialysis. Most patients will
recover kidney function and be able to discontinue
dialysis.
Some studies have shown that the use of antibiotics
and antimotility agents during an E. coli infection
1754

KEY TERMS
Antineoplastics—Agents that inhibit or prevent the
development, maturation, and proliferation of
malignant cells.
Gastroenteritis—An acute inflammation of the lining of the stomach and intestines, characterized by
nausea, diarrhea, abdominal pain and weakness,
which has various causes, including food poisoning
due to infection with such organisms as Escherichia
coli, Staphylococcus aureus and Salmonella species, consumption of irritating food or drink, or
psychological factors such as anger, stress and fear.

may worsen the course of the infection and should be
avoided. However, other studies have been less definitive. Physicians should stay informed so that clinical
practices matches medical advances on this aspect of
treatment.

Alternative treatment
Persons with HUS must be under the care
of health care professionals skilled in the treatment
of HUS.

Prognosis
Ninety percent of children with HUS who receive
careful supportive care survive the initial acute stages
of the condition, with most having no long-term
effects. However, between 10 and 30 percent of the
survivors will have kidney damage that will lead to
kidney failure immediately or within several years.
These children with kidney failure require on-going
dialysis to remove wastes and extra fluids from their
bodies, or may require a kidney transplant.

Prevention
Prevention of HUS caused by ingestion of foods
contaminated with E. coli O157:H7 and other toxinproducing bacteria is accomplished through practicing hygienic food preparation techniques, including
adequate handwashing, cooking of meat thoroughly,
defrosting meats safely, vigorous washing of fruits
and vegetables, and handling leftovers properly.
Irradiation of meat has been approved by the United
States Food and Drug Administration and the United
States Department of Agriculture in order to decrease
bacterial contamination of consumer meat supplies.
GALE ENCYCLOPEDIA OF MEDICINE

OTHER

National Kidney and Urologic Diseases Information
Clearinghouse. Fact Sheet: Hemolytic Uremic Syndrome.
NIH Publication No. 99-4570. March 2000. <http://
www.niddk.nih.gov/health/kidney/summary/hus/>.

Hemophilia A is the most common type of bleeding
disorder and involves decreased activity of factor VIII.
There are three levels of factor VIII deficiency: severe,
moderate, and mild. This classification is based on the
percentage of normal factor VIII activity present:


Individuals with less than 1% of normal factor VIII
activity level have severe hemophilia. Half of all
people with hemophilia A fall into this category.
Such individuals frequently experience spontaneous
bleeding, most frequently into their joints, skin, and
muscles. Surgery or trauma can result in lifethreatening hemorrhage, and must be carefully
managed.



Individuals with 1–5% of normal factor VIII activity
level have moderate hemophilia, and are at risk for
heavy bleeding after seemingly minor traumatic injury.



Individuals with 5–40% of normal factor VIII activity level have mild hemophilia, and must prepare
carefully for any surgery or dental procedures.

Judith Sims

Hemophilia
Definition
Hemophilia is a genetic disorder—usually inherited—of the mechanism of blood clotting. Depending
on the degree of the disorder present in an individual,
excess bleeding may occur only after specific, predictable events (such as surgery, dental procedures, or
injury), or occur spontaneously, with no known initiating event.

Description
The normal mechanism for blood clotting is a
complex series of events involving the interaction of
the injured blood vessel, blood cells (called platelets),
and over 20 different proteins which also circulate in
the blood.
When a blood vessel is injured in a way that causes
bleeding, platelets collect over the injured area, and
form a temporary plug to prevent further bleeding.
This temporary plug, however, is too disorganized to
serve as a long-term solution, so a series of chemical
events occur, resulting in the formation of a more reliable plug. The final plug involves tightly woven fibers of
a material called fibrin. The production of fibrin
requires the interaction of several chemicals, in particular a series of proteins called clotting factors. At least
thirteen different clotting factors have been identified.
The clotting cascade, as it is usually called, is the
series of events required to form the final fibrin clot.
The cascade uses a technique called amplification to
rapidly produce the proper sized fibrin clot from the
small number of molecules initially activated by the
injury.
In hemophilia, certain clotting factors are either
decreased in quantity, absent, or improperly formed.
Because the clotting cascade uses amplification to
rapidly plug up a bleeding area, absence or inactivity of
just one clotting factor can greatly increase bleeding time.
GALE ENCYCLOPEDIA OF MEDICINE

Individuals with hemophilia B have symptoms
very similar to those of hemophilia A, but the deficient
factor is factor IX. This type of hemophilia is also
known as Christmas disease.
Hemophilia C is very rare, and much more mild
than hemophilia A or B; it involves factor XI.
Hemophilia A affects between one in 5,000 to one
in 10,000 males in most populations.
One recent study estimated the prevalence of
hemophilia was 13.4 cases per 100,000 U.S. males
(10.5 hemophilia A and 2.9 hemophilia B). By race/
ethnicity, the prevalence was 13.2 cases/100,000 among
white, 11.0 among African-American, and 11.5 among
Hispanic males.

Causes and symptoms
Hemophilia A and B are both caused by a genetic
defect present on the X chromosome. (Hemophilia C
is inherited in a different fashion.) About 70% of all
people with hemophilia A or B inherited the disease.
The other 30% develop from a spontaneous genetic
mutation.
The following concepts are important to understanding the inheritance of these diseases. All humans
have two chromosomes determining their gender:
females have XX, males have XY. Because the trait
is carried only on the X chromosome, it is called ‘‘sexlinked.’’ The chromosome’s flawed unit is referred to
as the gene.
Both factors VIII and IX are produced by a
genetic defect of the X chromosome, so hemophilia
1755

Hemophilia

Resources

Hemophilia

A and B are both sex-linked diseases. Because a female
child always receives two X chromosomes, she nearly
always will receive at least one normal X chromosome.
Therefore, even if she receives one flawed X chromosome, she will still be capable of producing a sufficient
quantity of factors VIII and IX to avoid the symptoms
of hemophilia. Such a person who has one flawed
chromosome, but does not actually suffer from the
disease, is called a carrier. She carries the flaw that
causes hemophilia and can pass it on to her offspring.
If, however, she has a son who receives her flawed
X chromosome, he will be unable to produce the
right quantity of factors VIII or IX, and he will suffer
some degree of hemophilia. (Males inherit one X and
one Y chromosome, and therefore have only one
X chromosome.)
In rare cases, a hemophiliac father and a carrier
mother can pass on the right combination of parental
chromosomes to result in a hemophiliac female child.
This situation, however, is rare. The vast majority of
people with either hemophilia A or B are male.
About 30% of all people with hemophilia A or B
are the first member of their family to ever have the
disease. These individuals have had the unfortunate
occurrence of a spontaneous mutation; meaning
that in their early development, some random genetic
accident befell their X chromosome, resulting in the
defect causing hemophilia A or B. Once such a spontaneous genetic mutation takes place, offspring of the
affected person can inherit the newly created, flawed
chromosome.
In the case of severe hemophilia, the first bleeding
event usually occurs prior to eighteen months of age.
In some babies, hemophilia is suspected immediately,
when a routine circumcision (removal of the foreskin
of the penis) results in unusually heavy bleeding.
Toddlers are at particular risk, because they fall frequently, and may bleed into the soft tissue of their
arms and legs. These small bleeds result in bruising
and noticeable lumps, but don’t usually need treatment. As a child becomes more active, bleeding may
occur into the muscles; a much more painful and
debilitating problem. These muscle bleeds result in
pain and pressure on the nerves in the area of the
bleed. Damage to nerves can cause numbness and
decreased ability to use the injured limb.
Some of the most problematic and frequent bleeds
occur into the joints, particularly into the knees and
elbows. Repeated bleeding into joints can result in
scarring within the joints and permanent deformities.
Individuals may develop arthritis in joints that have
suffered continued irritation from the presence of
1756

blood. Mouth injuries can result in compression of
the airway, and, therefore, can be life-threatening. A
blow to the head, which might be totally insignificant
in a normal individual, can result in bleeding into the
skull and brain. Because the skull has no room for
expansion, the hemophiliac individual is at risk for
brain damage due to blood taking up space and exerting pressure on the delicate brain tissue.
People with hemophilia are at very high risk of
hemorrhage (severe, heavy, uncontrollable bleeding)
from injuries such as motor vehicle accidents and also
from surgery.
Some other rare clotting disorders such as Von
Willebrand disease present similar symptoms but are
not usually called hemophilia.

Diagnosis
Various tests are available to measure, under very
carefully controlled conditions, the length of time it
takes to produce certain components of the final fibrin
clot. Tests called assays can also determine the percentage of factors VIII and IX present compared to normal percentages. This information can help in
demonstrating the type of hemophilia present, as well
as the severity.
Individuals with a family history of hemophilia
may benefit from genetic counseling before deciding
to have a baby. Families with a positive history of
hemophilia can also have tests done during a pregnancy to determine whether the fetus is a hemophiliac.
The test called chorionic villous sampling examines
proteins for the defects that lead to hemophilia. This
test, which is associated with a 1% risk of miscarriage,
can be performed at 10–14 weeks. The test called amniocentesis examines the DNA of fetal cells shed into the
amniotic fluid for genetic mutations. Amniocentesis,
which is associated with a one in 200 risk of miscarriage,
is performed at 15–18 weeks gestation.

Treatment
The most important thing that individuals with
hemophilia can do to prevent complications of this
disease is to avoid injury. Those individuals who
require dental work or any surgery may need to be
pre-treated with an infusion of factor VIII to avoid
hemorrhage. Also, hemophiliacs should be vaccinated
against hepatitis. Medications or drugs that promote
bleeding, such as aspirin, should be avoided.
Various types of factors VIII and IX are available
to replace a patient’s missing factors. These are administered intravenously (directly into the patient’s veins
GALE ENCYCLOPEDIA OF MEDICINE

Hemophilia

Carrier mother

XY

XX
X

XY

XX

XY

XX

No gene
no symptoms

No gene
no symptoms

Inherited gene
has symptoms

Inherited gene
no symptoms

Transmission by a carrier mother

Hemophiliac father

XY

XX

XY

XX

XY

XX

No gene
no symptoms

Inherited gene
no symptoms

No gene
no symptoms

Inherited gene
no symptoms

Transmission by a hemophiliac father
Hemophilia A and B are both caused by a genetic defect present on the X chromosome. Approximately 70% of people with
hemophilia A or B inherited the disease, while the remaining 30% have hemophilia due to a spontaneous genetic mutation.
(Illustration by Electronic Illustrators Group.)

by needle). These factor preparations may be obtained
from a single donor, by pooling the donations of as
many as thousands of donors, or by laboratory creation through highly advanced genetic techniques.

treatment in the event of injury, or to prepare for
scheduled surgical or dental procedures. Patients
with more severe disease will require regular treatment
to avoid spontaneous bleeding.

The frequency of treatment with factors depends
on the severity of the individual patient’s disease.
Patients with relatively mild disease will only require

While appropriate treatment of hemophilia can
both decrease suffering and be life-saving, complications associated with treatment can also be quite

GALE ENCYCLOPEDIA OF MEDICINE

1757

Hemophilia

KEY TERMS
Amplification—A process by which something is
made larger. In clotting, only a very few chemicals
are released by the initial injury; they result in a
cascade of chemical reactions which produces
increasingly larger quantities of different chemicals, resulting in an appropriately-sized, strong
fibrin clot.
Factors—Coagulation factors are substances in the
blood, such as proteins and minerals, that are
necessary for clotting. Each clotting substance is
designated with roman numerals I through XIII.
Fibrin—The final substance created through the
clotting cascade, which provides a strong, reliable
plug to prevent further bleeding from the initial
injury.
Hemorrhage—Very severe, massive bleeding that
is difficult to control. Hemorrhage can occur in
hemophiliacs after what would be a relatively
minor injury to a person with normal clotting
factors.
Mutation—A permanent change in the genetic
material that may alter a trait or characteristic of
an individual, or manifest as disease, and can be
transmitted to offspring.
Platelets—Small disc-shaped structures that circulate in the blood stream and participate in blood
clotting.
Trauma—Injury.

statistics show that HIV is still the leading cause
of death among hemophiliacs. Currently, careful
methods of donor testing, as well as methods of
inactivating viruses present in donated blood, have
greatly lowered this risk.
The most exciting new treatments currently being
researched involve efforts to transfer new genes to
hemophiliacs. These new genes would have the ability
to produce the missing factors. As yet, these techniques are not being performed on humans, but there
is great hope that eventually this type of gene therapy
will be available.

Prognosis
Prognosis is very difficult to generalize. Because
there are so many variations in the severity of hemophilia, and because much of what befalls a hemophiliac patient will depend on issues such as physical
activity level and accidental injuries, statistics on prognosis are not generally available.
Resources
BOOKS

Khoury, Muin J., Wylie Burke, and Elizabeth J. Thomson,
editors. Genetics and Public Health in the 21st Century:
Using Genetic Information to Improve Health and
Prevent Disease. New York: Oxford University
Press, 2000.
Resnick, Susan. Blood Saga: Hemophilia, AIDS, and the
Survival of a Community. Berkeley: University of
California Press, 1999.
PERIODICALS

serious. About 20% of all patients with hemophilia A
begin to produce chemicals in their bodies which
rapidly destroy infused factor VIII. The presence of
such a chemical may greatly hamper efforts to prevent
or stop a major hemorrhage.
Individuals who receive factor prepared from
pooled donor blood are at risk for serious infections
that may be passed through blood. Hepatitis, a
severe and potentially fatal viral liver infection,
may be contracted from pooled factor preparations.
Recently, a good deal of concern has been raised
about the possibility of hemophiliacs contracting a
fatal slow virus infection of the brain (CreutzfeldtJakob disease) from blood products. Unfortunately,
pooled factor preparations in the early 1980s were
contaminated with human immunodeficiency virus
(HIV), the virus which causes AIDS. A large number
of hemophiliacs were infected with HIV and some
1758

Stephenson, J. ‘‘New Therapies Show Promise for Patients
with Leukemia, Hemophilia, and Heart Disease.’’
JAMA 285 (January 1, 2001): 153+.
ORGANIZATIONS

National Hemophilia Foundation. 116 West 32nd St., 11th
Floor, New York, NY 10001. (800) 42-HANDI.
<http://www.info@hemophilia.org>.
National Organization for Rare Disorders (NORD). PO
Box 8923, New Fairfield, CT 06812-8923. (203)
746-6518 or (800) 999-6673. Fax: (203) 746-6481.
<http://www.rarediseases.org>.
OTHER

March of Dimes. <www.modimes.org>.
National Organization for Rare Disorders.
<www.rarediseases.org>.

Jennifer F. Wilson, MS

Hemophilus ducreyi infection see Chancroid
GALE ENCYCLOPEDIA OF MEDICINE

Hemophilus infections
Definition
Hemophilus infections, most of which are due to
Haemophilus influenzae infections, are a group of contagious diseases that are caused by a gram-negative
bacterium, and affect only humans. Some hemophilus
infections are potentially fatal.

Description
H. influenzae is a common organism worldwide;
it has been found in the nasal secretions of as many as
90% of healthy individuals in the general population.
Hemophilus infections are characterized by acute
inflammation with a discharge (exudate). They may
affect almost any organ system, but are most common
in the respiratory tract. The organism can be transmitted by person-to-person contact, or by contact
with nasal discharges and other body fluids.
Hemophilus infections in the United States are most
likely to spread in the late winter or early spring.
The primary factor influencing the rate of infection is age; children between the ages of six months
and four years are most vulnerable to H. influenzae. In
previous years, about 50% of children would acquire a
hemophilus infection before reaching one year of age;
almost all children would develop one before age
three. These figures are declining, however, as a result
of the increasing use of hemophilus vaccines for
children.
Adults are also susceptible to hemophilus diseases. H. influenzae pneumonia is a common nosocomial infection (illnesses contracted in hospitals). The
rate of hemophilus infections in the adult population
has increased over the past 40 years. The reasons
for this change are unclear, but some researchers speculate that the overuse of antibiotics has led to the
development of drug-resistant strains of H. influenzae.
The risk factors for hemophilus infections among
adults include:


smoking



alcoholism



chronic lung disease



old age



living in a city or institutional housing with a large
group of people



poor nutrition and hygiene



hIV infection, or other immune system disorder

GALE ENCYCLOPEDIA OF MEDICINE

Hemophilus infections are primarily caused by
Haemophilus influenzae, a gram-negative bacterium
that is capable of spreading from the nasal tissues
and upper airway, where it is usually found, to the
chest, throat, or middle ear. The organism sometimes
invades localized areas of tissue, producing meningitis,
infectious arthritis, conjunctivitis, cellulitis, epiglottitis,
or inflammation of the membrane surrounding the
heart. The most serious infections are caused by a
strain called H. influenzae b (Hib). Before routine
vaccination, Hib was the most common cause of
bacterial meningitis, and responsible for most of the
cases of acquired mental retardation in the United
States.
Hemophilus infections in children
BACTERIAL SEPSIS IN THE NEWBORN. Bacterial
sepsis (sepsis is the presence of illness-causing microorganisms, or their poisons, in the blood) is a potentially fatal illness in newborn infants. The child may
acquire the disease organism as it passes through
the mother’s birth canal, or from the hospital environment. H. influenzae can also produce inflammations of the eye (conjunctivitis) in newborn children.
The signs of sepsis may include fever, crankiness,
feeding problems, breathing difficulties, pale or
mottled skin, or drowsiness. Premature birth is the
most significant risk factor for hemophilus infections in newborns.
EPIGLOTTITIS. Epiglottitis is a potentially fatal
hemophilus infection. Although children are more
likely to develop epiglottitis, it can occur in adults as
well. When the epiglottis (a piece of cartilage behind
the tongue which protects the opening to the windpipe
by opening and closing) is infected, it can swell to
the point where it blocks the windpipe. The symptoms
of epiglottitis include a sudden high fever, drooling,
the feeling of an object stuck in the throat, and stridor.
The epiglottis will look swollen and bright red if the
doctor examines the patient’s throat with a laryngoscope (a viewing device).
MENINGITIS. Meningitis caused by Hib is most
common in children between nine months and four
years of age. The child usually develops upper respiratory symptoms followed by fever, loss of appetite,
vomiting, headache, and a stiff or sore neck or back.
In severe cases, the child may have convulsions or go
into shock or coma.
OTHER INFECTIONS. Hib is the second most common cause of middle ear infection and sinusitis in

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Hemophilus infections

Causes and symptoms

Hemophilus infections

children. The symptoms of sinusitis include fever,
pain, bad breath, and coughing. Children may also
develop infectious arthritis from Hib. The joints
most frequently affected are the large weight-bearing
joints.
Hemophilus infections in adults
PNEUMONIA. Hib pneumonia is the most common hemophilus infection in adults. The symptoms
include empyema (sputum containing pus), and fever.
The hemophilus organism can usually be identified
from sputum samples. Hib pneumonia is increasingly
common in the elderly.
MENINGITIS. Meningitis caused by Hib can
develop in adults as a complication of an ear infection
or sinusitis. The symptoms are similar to those in
children but are usually less severe in adults.

Diagnosis
The diagnosis is usually based on a combination
of the patient’s symptoms and the results of blood
counts, cultures, or antigen detection tests.
Laboratory tests
Laboratory tests can be used to confirm the diagnosis of hemophilus infections. The bacterium can
be grown on chocolate agar, or identified by blood
cultures or Gram stain of body fluids. Antigen detection tests can be used to identify hemophilus infections
in children. These tests include latex agglutination
and electrophoresis.
Other laboratory findings that are associated
with hemophilus infections include anemia (low red
blood cell count), and a drop in the number of white
blood cells in children with severe infections. Adults
often show an abnormally high level of white blood
cells; cell counts of 15,000–30,000/mm3 are not
unusual.

Treatment
Because some hemophilus infections are potentially fatal, treatment is started without waiting for
the results of laboratory tests.
Medications
Hemophilus infections are treated with antibiotics. Patients who are severely ill are given ampicillin
or a third-generation cephalosporin, such as cefotaxime or ceftriaxone, intravenously. Patients with
milder infections are given oral antibiotics, including
1760

amoxicillin, cefaclor, erythromycin, or trimethoprim-sulfamethoxazole. Patients who are allergic to
penicillin are usually given cefaclor or trimethoprimsulfamethoxazole.
Patients with Hib strains that are resistant to ampicillin may be given chloramphenicol. Chloramphenicol
is not a first-choice drug because of its side effects,
including interference with bone marrow production
of blood cells.
The duration of antibiotic treatment depends on
the location and severity of the hemophilus infection.
Adults with respiratory tract infections, or Hib pneumonia, are usually given a 10–14 day course of antibiotics. Meningitis is usually treated for 10–14 days,
but a seven-day course of treatment with ceftriaxone
appears to be sufficient for infants and children. Ear
infections are treated for seven to 10 days.
Supportive care
Patients with serious hemophilus infections
require bed rest and a humidified environment (such
as a croup tent) if the respiratory tract is affected.
Patients with epiglottitis frequently require intubation
(insertion of a breathing tube) or a tracheotomy to
keep the airway open. Patients with inflammation of
the heart membrane, pneumonia, or arthritis may
need surgical treatment to drain infected fluid from
the chest cavity or inflamed joints.
Supportive care also includes monitoring of blood
cell counts for patients using chloramphenicol, ampicillin, or other drugs that may affect production of
blood cells by the bone marrow.

Prognosis
The most important factors in the prognosis are
the severity of the infection and promptness of treatment. Untreated hemophilus infections—particularly
meningitis, sepsis, and epiglottitis—have a high mortality rate. Bacterial sepsis of the newborn has a mortality rate between 13–50%. The prognosis is usually
good for patients with mild infections who are treated
without delay. Children who develop Hib arthritis
sometimes have lasting problems with joint function.

Prevention
Hemophilus vaccines
There are three different vaccines for hemophilus
infections used to immunize children in the United
States: PRP-D, HBOC, and PRP-OMP. PRP-D is used
only in children older than 15 months. HBOC is
GALE ENCYCLOPEDIA OF MEDICINE

Bacterium—A microscopic one-celled organism.
Haemophilus influenzae is a specific bacterium.
Epiglottitis—Inflammation of the epiglottis. The
epiglottis is a piece of cartilage behind the tongue
that closes the opening to the windpipe when a
person swallows. An inflamed epiglottis can swell
and close off the windpipe, thus causing the patient
to suffocate.
Exudate—A discharge produced by the body.
Some exudates are caused by infections.

BOOKS

Chambers, Henry F. ‘‘Infectious Diseases: Bacterial &
Chlamydial.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al.,
37th ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Hemophilus influenzae infections see
Hemophilus infections

Gram-negative—A term that means that a bacterium will not retain the violet color when stained
with Gram’s dye. Haemophilus influenzae is a
gram-negative bacterium.
Intubation—The insertion of a tube into the
patient’s airway to protect the airway from collapsing. Intubation is sometimes done as an emergency procedure for patients with epiglottitis.
Nosocomial—Contracted in a hospital. Pneumonia
caused by H. influenzae is an example of a nosocomial infection.
Sepsis—Invasion of body tissues by disease organisms or their toxins. Sepsis may be either localized
or generalized. Haemophilus influenzae can cause
bacterial sepsis in newborns.
Stridor—A harsh or crowing breath sound caused
by partial blockage of the patient’s upper airway.
Tracheotomy—An emergency procedure in
which the surgeon cuts directly through the
patient’s neck into the windpipe in order to keep
the airway open.

administered to infants at two, four, and six months after
birth, with a booster dose at 15–18 months. PRP-OMP is
administered to infants at two and four months, with
the third dose at the child’s first birthday. All three
vaccines are given by intramuscular injection. About
5% of children may develop fever or soreness in the
area of the injection.
Other measures
Other preventive measures include isolating
patients with respiratory hemophilus infections; treating appropriate contacts of infected patients with
rifampin; maintaining careful standards of cleanliness
in hospitals, including proper disposal of soiled tissues; and washing hands properly.
GALE ENCYCLOPEDIA OF MEDICINE

Hemoptysis
Definition
Hemoptysis is the coughing up of blood or bloody
sputum from the lungs or airway. It may be either selflimiting or recurrent. Massive hemoptysis is defined
as 200–600 mL of blood coughed up within a period of
24 hours or less.

Description
Hemoptysis can range from small quantities of
bloody sputum to life-threatening amounts of blood.
The patient may or may not have chest pain.

Causes and symptoms
Hemoptysis can be caused by a range of disorders:


Infections. These include pneumonia; tuberculosis;
aspergillosis; and parasitic diseases, including ascariasis, amebiasis, and paragonimiasis.



Tumors that erode blood vessel walls.



Drug abuse. Cocaine can cause massive hemoptysis.



Trauma. Chest injuries can cause bleeding into the
lungs.



Vascular disorders, including aneurysms, pulmonary
embolism, and malformations of the blood vessels.



Bronchitis. Its most common cause is long-term
smoking.



Foreign object(s) in the airway.



Blood clotting disorders.



Bleeding following such surgical procedures as bronchial biopsies and heart catheterization.
1761

Hemoptysis

Resources

KEY TERMS

Hemoptysis

Diagnosis
The diagnosis of hemoptysis is complicated by the
number of possible causes.
Patient history
It is important for the doctor to distinguish
between blood from the lungs and blood coming
from the nose, mouth, or digestive tract. Patients may
aspirate, or breathe, blood from the nose or stomach
into their lungs and cough it up. They may also swallow
blood from the chest area and then vomit. The doctor
will ask about stomach ulcers, repeated vomiting, liver
disease, alcoholism, smoking, tuberculosis, mitral valve
disease, or treatment with anticoagulant medications.
Physical examination
The doctor will examine the patient’s nose, throat,
mouth, and chest for bleeding from these areas and for
signs of chest trauma. The doctor also listens to the
patient’s breathing and heartbeat for indications of
heart abnormalities or lung disease.
Laboratory tests
Laboratory tests include blood tests to rule out
clotting disorders, and to look for food particles or
other evidence of blood from the stomach. Sputum
can be tested for fungi, bacteria, or parasites.
X ray and bronchoscopy
Chest x rays and bronchoscopy are the most
important studies for evaluating hemoptysis. They
are used to evaluate the cause, location, and extent of
the bleeding. The bronchoscope is a long, flexible tube
used to identify tumors or remove foreign objects.
Imaging and other tests
Computed tomography scans (CT scans) are used
to detect aneurysms and to confirm x-ray results.
Ventilation-perfusion scanning is used to rule out
pulmonary embolism. The doctor may also order an
angiogram to rule out pulmonary embolism, or to
locate a source of bleeding that could not be seen
with the bronchoscope.
In spite of the number of diagnostic tests, the cause
of hemoptysis cannot be determined in 20–30%
of cases.

Treatment
Massive hemoptysis is a life-threatening emergency that requires treatment in an intensive care
1762

KEY TERMS
Aneurysm—A sac formed by the dilation of the
wall of an artery, vein, or heart; it is filled with
clotted blood or fluid.
Angiography—A technique for imaging the blood
vessels by injecting a substance that is opaque to
x rays.
Aspergillosis—A lung infection caused by the mold
Aspergillus fumigatus.
Intubation—The insertion of a tube into a body
canal or hollow organ, as into the trachea or
stomach.
Pulmonary embolism—The blocking of an artery in
the lung by a blood clot.

unit. The patient will be intubated (the insertion of a
tube to help breathing) to protect the airway, and to
allow evaluation of the source of the bleeding. Patients
with lung cancer, bleeding from an aneurysm (blood
clot), or persistent traumatic bleeding require chest
surgery.
Patients with tuberculosis, aspergillosis, or bacterial pneumonia are given antibiotics.
Foreign objects are removed with a bronchoscope.
If the cause cannot be determined, the patient is
monitored for further developments.

Prognosis
The prognosis depends on the underlying cause.
In cases of massive hemoptysis, the mortality rate
is about 15%. The rate of bleeding, however, is not
a useful predictor of the patient’s chances for recovery.
Resources
BOOKS

Stauffer, John L. ‘‘Lung.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al.,
37th ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Hemorrhagic colitis see Escherichia coli
Hemorrhagic fever with renal syndrome see
Hantavirus infections
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Hemorrhagic fevers are caused by viruses that
exist throughout the world. However, they are most
common in tropical areas. Early symptoms, such as
muscle aches and fever, can progress to a mild illness
or to a more debilitating, potentially fatal disease. In
severe cases, a prominent symptom is bleeding, or
hemorrhaging, from orifices and internal organs.

Causes and symptoms
The viruses that cause hemorrhagic fevers are
found most commonly in tropical locations; however,
some are found in cooler climates. Typical disease
vectors include rodents, ticks, or mosquitoes, but person-to-person transmission in health care settings or
through sexual contact can also occur.

Description
Although hemorrhagic fevers are regarded as
emerging diseases, they probably have existed for
many years. This designation isn’t meant to imply
that they are newly developing, but rather that
human exposure to the causative viruses is increasing
to the point of concern.
These viruses are maintained in nature in arthropod (insects, spiders and other invertebrates with
external hard skeletons) or animal populations—
so-called disease reservoirs. Individuals within these
populations become infected with a virus but do not
die from it. In many cases, they don’t even develop
symptoms. Then the viruses are transmitted from a
reservoir population to humans by vectors—either
members of the reservoir population or an intervening
species, such as mosquitoes.
Hemorrhagic fevers are generally either endemic
or linked to specific locations. If many people reside
in an endemic area, the number of cases may soar.
For example, dengue fever, a type of hemorrhagic fever,
affects approximately 100 million people annually.
A large percentage of those infected live in densely
populated southeast Asia; an area in which the disease
vector, a mosquito, thrives. Some hemorrhagic fevers
are exceedingly rare, because people very infrequently
encounter the virus. Marburg hemorrhagic fever,
which has affected fewer than 40 people since its discovery in 1967, provides one such example. Fatality
rates are also variable. In cases of dengue hemorrhagic
fever–dengue shock syndrome, 1–5% of the victims
perish. On the other end of the spectrum is Ebola,
an African hemorrhagic fever, that kills 30–90% of
those infected.
The onset of hemorrhagic fevers may be sudden or
gradual, but all of them are linked by the potential for
hemorrhaging. However, not all cases progress to this
very serious symptom. Hemorrhaging may be attributable to the destruction of blood coagulating factors
GALE ENCYCLOPEDIA OF MEDICINE

Filoviruses
Ebola is the most famous of the Filoviridae, a
virus family that also includes the Marburg virus.
Ebola is endemic to Africa, particularly the Republic
of the Congo and Sudan; the Marburg virus is found
in sub-Saharan Africa. The natural reservoir of filoviruses is unknown. The incubation period, or time
between infection and appearance of symptoms, is
thought to last three to eight days, possibly longer.
Symptoms appear suddenly, and include severe
headache, fever, chills, muscle aches, malaise, and
appetite loss. These symptoms may be accompanied
by nausea, vomiting, diarrhea, and abdominal pain.
Victims become apathetic and disoriented. Severe
bleeding commonly occurs from the gastrointestinal
tract, nose and throat, and vagina. Other bleeding
symptoms include petechiae and oozing from injection
sites. Ebola is fatal in 30–90% of cases.
Arenaviruses
Viruses of the Arenaviridae family cause the
Argentinian, Brazilian, Bolivian, and Venezuelan
hemorrhagic fevers. Lassa fever, which occurs in west
Africa, also arises from an arenavirus. Infected
rodents, the natural reservoir, shed virus particles in
their urine and saliva, which humans may inhale or
otherwise come in contact with.
Fever, muscle aches, malaise, and appetite loss
gradually appear one to two weeks after infection
with the South American viruses. Initial symptoms
are followed by headache, back pain, dizziness, and
gastrointestinal upset. The face and chest appear
flushed and the gums begin to bleed. In about 30%
of cases, the disease progresses to bleeding under the
skin and from the mucous membranes, and/or to
effects on the nervous system, such as delirium,
coma, and convulsions. Untreated, South American
hemorrhagic fevers have a 10–30% fatality rate.
1763

Hemorrhagic fevers

Hemorrhagic fevers

or to increased permeability of body tissues. The severity of bleeding ranges from petechiae, which are pinpoint hemorrhages under the skin surface, to distinct
bleeding from such body orifices as the nose or vagina.

Hemorrhagic fevers

Lassa fever also begins gradually, following an
8–14 day incubation. Initial symptoms resemble
those of the South American hemorrhagic fevers,
followed by a sore throat, muscle and joint pain, severe
headache, pain above the stomach, and a dry cough.
The face and neck become swollen, and fluid may
accumulate in the lungs. Bleeding occurs in 15–20%
of infected individuals, mostly from the gums and
nose. Overall, the fatality rate is lower than 2%, but
hospitals may encounter 20% fatality rates, treating
typically the most serious of cases.
Flaviviruses
The Flaviviridae family includes the viruses that
cause yellow and dengue fevers.
Yellow fever occurs in tropical areas of the
Americas and Africa and is transmitted from monkeys
to humans by mosquitoes. The virus may produce a
mild, possibly unnoticed illness, but some individuals
are suddenly stricken with a fever, weakness, low back
pain, muscle pain, nausea, and vomiting. This phase
lasts one to seven days, after which the symptoms
recede for one to two days. Symptoms then return
with greater intensity, along with jaundice, delirium,
seizures, stupor, and coma. Bleeding occurs from the
mucous membranes and under the skin surface, and
dark blood appears in stools and vomit.
Mosquitoes also transmit the dengue virus.
Dengue fever is endemic in southeast Asia and areas
of the Americas. Cases have also been reported in the
Caribbean, Saudi Arabia, and northern Australia. In
2004 several cases were reported along the border
between Texas and Mexico in the southwestern
United States. This virus causes either the mild dengue
fever or the more serious dengue hemorrhagic fever–
dengue shock syndrome (DHF-DSS).
In children, dengue fever is characterized by a sore
throat, runny nose, slight cough, and a fever lasting for
a week or less. Older children and adults experience
more severe symptoms: fever, headache, muscle and
joint pain, loss of appetite, and a rash. The skin
appears flushed, and intense pain occurs in the bones
and limbs. After nearly a week, the fever subsides for
one to two days before returning. Minor hemorrhaging, such as from the gums, or more serious gastrointestinal bleeding may occur.
DHF-DSS primarily affects children younger
than 15 years. The symptoms initially resemble those
of dengue fever in adults, without the bone and limb
pain. As the fever begins to abate, the individual’s
condition worsens and hemorrhaging occurs from
the nose, gums, and injection sites. Bleeding is also
1764

seen from the gastrointestinal, genitourinary, and
respiratory tracts.
Bunyaviruses
The Bunyaviridae family includes several hundred
viruses but only a few are responsible for hemorrhagic
fevers in humans.
Rift Valley fever is caused by the phlebovirus,
found in sub-Saharan Africa and the Nile delta.
Natural reservoirs are wild and domestic animals,
and transmission occurs through contact with
infected animals or through mosquito bites. The
incubation period lasts 3–12 days. Most cases of
Rift Valley fever are mild and may be symptomless.
If symptoms develop, they include fever, backache,
muscle and joint pain, and headache. Hemorrhagic
symptoms occur rarely; while death, which occurs in
fewer than 3% of cases, is attributable to massive
liver damage.
Crimean-Congo hemorrhagic fever is caused by
nairovirus and occurs in central and southern Africa,
Asia, Eurasia, and the Middle East. The virus is found
in hares, birds, ticks, and domestic animals and may be
transmitted by ticks or by contact with infected animals. The nairovirus incubation period is three to
12 days; after which an individual experiences fever,
chills, headache, severe muscle pain, pain above
the stomach, nausea, vomiting, and appetite loss.
Bleeding under the skin and gastrointestinal and vaginal bleeding may develop in the most severe cases.
Death rates range from 10% in southern Russia
to 50% in parts of Asia.
Hemorrhagic fever with renal (kidney) syndrome
is caused by the hantaviruses: Hantaan, Seoul,
Puumala, and Dobrava. Hantaan virus occurs in
northern Asia, the Far East, and the Balkans; Seoul
virus is found worldwide; Puumala virus is found
in Scandinavia and northern Europe; while Dobrava
virus occurs in the Balkans. Wild rodents are the
natural reservoirs and transmit the virus via their
excrement or body fluids or through direct contact.
Initial symptoms develop within 10–40 days and
include fever, headache, muscle pain, and dizziness.
Other symptoms are blurry vision, abdominal and
back pain, nausea, and vomiting. High levels of protein in the urine signal kidney damage; hemorrhaging
may also occur. Death rates range from 0–10%.

Diagnosis
Since the hemorrhagic fevers share symptoms
with many other diseases, positive identification of
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Lassa fever, and possibly other hemorrhagic
fevers, respond to ribavirin, an antiviral medication.
However, most of the hemorrhagic fever viruses
can only be treated with supportive care. Interferon
is not useful and may in fact complicate management. Such care centers around maintaining correct
fluid and electrolyte balances in the body and protecting the patient against secondary infections.
Heparin and vitamin K administration, coagulation
factor replacement, and blood transfusions may be
effective in lessening or stopping hemorrhage in
some cases.
Some researchers are investigating the possibility
of targeting tissue factor (TF) as a way of treating viral
hemorrhagic fevers. TF is a protein that activates the
coagulation process in these illnesses, and experimental models suggest that a blockade of tissue factor
assists the body’s immune response to hemorrhagic
fever viruses.

Prognosis
Recovery from some hemorrhagic fevers is more
certain than from others. The filoviruses are among
the most lethal; fatality rates for Ebola range from
30–90%, while DHF-DSS cases result in a 1–5% fatality rate. Whether a case occurs during an epidemic
or as an isolated case also has a bearing on the outcome. For example, isolated cases of yellow fever have
a 5% mortality rate, but 20–50% of epidemic cases
may be fatal.
Permanent disability can occur with some types of
hemorrhagic fever. About 10% of severely ill Rift
Valley fever victims suffer retina damage and may be
permanently blind, and 25% of South American
hemorrhagic fever victims suffer potentially permanent deafness.
Proper treatment is vital. In cases of DHF-DSS,
fatality can be reduced from 40–50% to less than 2%
with adequate medical care. For individuals who
survive hemorrhagic fevers, prolonged convalescence is usually inevitable. However, survivors seem
to gain lifelong immunity against the virus that made
them ill.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Antibody—A molecule created by the body’s
immune system to combat a specific infectious
agent, such as a virus or bacteria.
Antigen—A specific feature, such as a protein, on
an infectious agent. Antibodies use this feature as a
means of identifying infectious intruders.
Coagulating factors—Components within the
blood that help form clots.
Endemic—Referring to a specific geographic area
in which a disease may occur.
Hemorrhage—As a noun, this refers to the point at
which blood is released. As a verb, this refers to
bleeding.
Incubation—The time period between exposure to
an infectious agent, such as a virus or bacteria, and
the appearance of symptoms of illness.
Petechiae—Pinpoint hemorrhages that appear as
reddish dots beneath the surface of the skin.
Reservoir—A population in which a virus is maintained without causing serious illness to the
infected individuals.
Ribavirin—A drug that is used to combat viral
infections.
Tissue factor—A glycoprotein involved in blood
coagulation.
Vector—A member of the reservoir population
or an intervening species that can transmit a virus
to a susceptible victim. Mosquitoes are common
vectors, as are ticks and rodents.

Prevention
Hemorrhagic fevers can be prevented through
vector control and personal protection measures.
Attempts have been made in urban and settled areas
to destroy mosquito and rodent populations. In areas
where such measures are impossible, individuals can
use insect repellents, mosquito netting, and other
methods to minimize exposure.
Vaccines have been developed against yellow
fever, Argentinian hemorrhagic fever, and CrimeanCongo hemorrhagic fever. Vaccines against other
hemorrhagic fevers are being researched. Another
possible preventive measure is increasing the number
of natural killer (NK) cells in the body. These cells
appear to be an important innate source of protection
against Ebola and other filoviruses.
1765

Hemorrhagic fevers

the disease relies on evidence of the viruses in
the bloodstream—such as detection of antigens and
antibodies—or isolation of the virus from the
body. Disruptions in the normal levels of bloodstream
components may be helpful in determining some, but
not all, hemorrhagic fevers.

Hemorrhoids

Prevention of epidemics of hemorrhagic fevers has
acquired a new importance in the early 2000s from
concern that the causative viruses might be used as
weapons of bioterrorism. These viruses can be transmitted in aerosol form as well as having a high mortality rate.

Centers for Disease Control and Prevention, Special
Pathogens Branch. ‘‘Marburg Hemorrhagic Fever,’’
August 23, 2004. <http://www.cdc.gov/ncidod/dvrd/
spb/mnpages/dispages/marburg.htm>.

Julia Barrett
Rebecca J. Frey, PhD

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Viral Diseases.’’ Section 13, Chapter 162 In The
Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Izadi, S., K. H. Naieni, S. R. Madjdzadeh, and
A. Nadim. ‘‘Crimean-Congo Hemorrhagic Fever in
Sistan and Baluchestan Province of Iran, A CaseControl Study on Epidemiological Characteristics.’’
International Journal of Infectious Diseases 8
(September 2004): 299–306.
Mahanty, S., and M. Bray. ‘‘Pathogenesis of Filoviral
Haemorrhagic Fevers.’’ Lancet Infectious Diseases 4
(August 2004): 487–498.
Ruf, W. ‘‘Emerging Roles of Tissue Factor in Viral
Hemorrhagic Fever.’’ Trends in Immunology 25
(September 2004): 461–464.
Salvaggio, M. R., and J. W. Baddley. ‘‘Other Viral
Bioweapons: Ebola and Marburg Hemorrhagic Fever.’’
Dermatologic Clinics 22 (July 2004): 291–302.
Setlick, R. F., D. Ouellette, J. Morgan, et al.
‘‘Pulmonary Hemorrhage Syndrome Associated with
an Autochthonous Case of Dengue Hemorrhagic
Fever.’’ Southern Medical Journal 97 (July 2004):
688–691.
Warfield, K. L., J. G. Perkins, D. L. Swenson, et al.
‘‘Role of Natural Killer Cells in Innate Protection
against Lethal Ebola Virus Infection.’’ Journal of
Experimental Medicine 200 (July 19, 2004):
169–179.

Hemorrhoids
Definition
Hemorrhoids are enlarged veins in the anus
or lower rectum. They often go unnoticed and
usually clear up after a few days, but can cause
long-lasting discomfort, bleeding and be excruciatingly painful. Effective medical treatments are available, however.

Description
Hemorrhoids (also called piles) can be divided
into two kinds, internal and external. Internal hemorrhoids lie inside the anus or lower rectum, beneath the
anal or rectal lining. External hemorrhoids lie outside
the anal opening. Both kinds can be present at the
same time.
Hemorrhoids are a very common medical complaint. More than 75% of Americans have hemorrhoids at some point in their lives, typically after
age 30. Pregnant women often develop hemorrhoids,
but the condition usually clears up after childbirth.
Men are more likely than women to suffer from
hemorrhoids that require professional medical
treatment.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
Infectious Diseases Society of America (IDSA). 66 Canal
Center Plaza, Suite 600, Alexandria, VA 22314. (703)
299-0200. Fax: (703) 299-0204. <http://
www.idsociety.org>.
World Health Organization (WHO). <http://www.
who.int/en/>.
OTHER

Centers for Disease Control and Prevention, Special
Pathogens Branch. ‘‘Ebola Hemorrhagic Fever,’’
August 23, 2004. <http://www.cdc.gov/ncidod/dvrd/
spb/mnpages/dispages/ebola.htm>.
1766

Causes and symptoms
Precisely why hemorrhoids develop is unknown.
Researchers have identified a number of reasons to
explain hemorrhoidal swelling, including the simple
fact that people’s upright posture places a lot of pressure on the anal and rectal veins. Aging, obesity, pregnancy, chronic constipation or diarrhea, excessive
use of enemas or laxatives, straining during bowel
movements, and spending too much time on the toilet
are considered contributing factors. Heredity may
also play a part in some cases. There is no reason to
believe that hemorrhoids are caused by jobs requiring,
for instance, heavy lifting or long hours of sitting,
GALE ENCYCLOPEDIA OF MEDICINE

Clinical photo of a thrombosed external hemorrhoid. (Custom
Medical Stock Photo. Reproduced by permission.)

although activities of that kind may make existing
hemorrhoids worse.
The commonest symptom of internal hemorrhoids is bright red blood in the toilet bowl or on
one’s feces or toilet paper. When hemorrhoids remain
inside the anus they are almost never painful, but they
can prolapse (protrude outside the anus) and become
irritated and sore. Sometimes, prolapsed hemorrhoids
move back into the anal canal on their own or can be
pushed back in, but at other times they remain permanently outside the anus until treated by a doctor.
Small external hemorrhoids usually do not produce symptoms. Larger ones, however, can be painful and interfere with cleaning the anal area after a
bowel movement. When, as sometimes happens, a
blood clot forms in an external hemorrhoid (creating
what is called a thrombosed hemorrhoid), the skin
around the anus becomes inflamed and a very painful lump develops. On rare occasions the clot will
begin to bleed after a few days and leave blood on
the underwear. A thrombosed hemorrhoid will not
cause an embolism.

Diagnosis
Diagnosis begins with a visual examination of the
anus, followed by an internal examination during
which the doctor carefully inserts a gloved and lubricated finger into the anus. The doctor may also use an
anoscope, a small tube that allows him or her to see
into the anal canal. Under some circumstances the
doctor may wish to check for other problems by
using a sigmoidoscope or colonoscope, a flexible
instrument that allows inspection of the lower colon
(in the case of the sigmoidoscope) or the entire colon
(in the case of the colonoscope).
GALE ENCYCLOPEDIA OF MEDICINE

Hemorrhoids can often be effectively dealt with
by dietary and lifestyle changes. Softening the feces
and avoiding constipation by adding fiber to one’s diet
is important, because hard feces lead to straining
during defecation. Fruit, leafy vegetables, and wholegrain breads and cereals are good sources of fiber, as
are bulk laxatives and fiber supplements such as
Metamucil or Citrucel. Exercising, losing excess
weight, and drinking six to eight glasses a day of
water or another liquid (not alcohol) also helps. Soap
or toilet paper that is perfumed may irritate the anal
area and should be avoided, as should excessive cleaning, rubbing, or wiping of that area. Reading in the
bathroom is also considered a bad idea, because it
adds to the time one spends on the toilet and may
increase the strain placed on the anal and rectal
veins. After each bowel movement, wiping with a
moistened tissue or pad sold for that purpose helps
lessen irritation. Hemorrhoid pain is often eased by
sitting in a tub of warm water for about 10 or
15 minutes two to four times a day (sitz bath). A cool
compress or ice pack to reduce swelling is also recommended (the ice pack should be wrapped in a cloth
or towel to prevent direct contact with the skin). Many
people find that over-the-counter hemorrhoid creams
and foams bring relief, but these medications do not
make hemorrhoids disappear.
When painful hemorrhoids do not respond to
home-based remedies, professional medical treatment
is necessary. The choice of treatment depends on the
type of hemorrhoid, what medical equipment is available, and other considerations.
Rubber band ligation is probably the most widely
used of the many treatments for internal hemorrhoids
(and the least costly for the patient). This procedure
is performed in the office of a family doctor or specialist, or in a hospital on an outpatient basis. An applicator is used to place one or two small rubber bands
around the base of the hemorrhoid, cutting off its
blood supply. After three to 10 days in the bands, the
hemorrhoid falls off, leaving a sore that heals in a week
or two. Because internal hemorrhoids are located in a
part of the anus that does not sense pain, anesthetic is
unnecessary and the procedure is painless in most
cases. Although there can be minor discomfort and
bleeding for a few days after the bands are applied,
complications are rare and most people are soon able
to return to work and other activities. If more than one
hemorrhoid exists or if banding is not entirely effective
the first time (as occasionally happens), the procedure
may need to be repeated a few weeks later. After five
years, 15–20% of patients experience a recurrence of
1767

Hemorrhoids

Treatment

Hemorrhoids

KEY TERMS

Hemorrhoid

Grasping
forceps
Rubberband
Ligator
Anoscope
Figure A

Anus—The opening at the lower end of the rectum.
The anus and rectum are both part of the large
intestine, a digestive system organ.
Colon—The major part of the large intestine, a
digestive system organ.
Defecation—Passage of feces through the anus.
Embolism—Obstruction of blood flow in an artery
by a blood clot or other substance arising from
another site. An untreated embolism can endanger
health and even cause death.
Enema—The introduction of water or another
liquid into the bowels through a tube inserted into
the anus. Enemas are used to treat constipation and
for other purposes.

Figure B

Rubber band ligation is probably the most widely used treatment for internal hemorrhoids. An applicator is used to place
one or two small rubber bands around the base of the hemorrhoid, cutting off its blood supply (figures A and B). After 3-10
days, the rubber bands and the hemorrhoid fall off, leaving a
scab which disappears within a week or two. (Illustration by
Electronic Illustrators Group.)

internal hemorrhoids, but in most cases all that is
needed is another banding.
External hemorrhoids, and some prolapsed internal hemorrhoids, are removed by conventional surgery in a hospital. Depending on the circumstances,
this requires a local, regional, or general anesthetic.
Surgery does cause a fair amount of discomfort, but an
overnight hospital stay is usually not necessary. Full
healing takes two to four weeks, but most people are
able to resume normal activities at the end of a week.
Hemorrhoids rarely return after surgery.

Alternative treatment
Like mainstream practitioners, alternative practitioners stress the importance of a high-fiber diet. To
prevent hemorrhoids by strengthening the veins of the
anus, rectum, and colon, they recommend blackberries,
blueberries, cherries, vitamin C, butcher’s broom
(Ruscus aculeatus), and flavonoids (plant pigments
1768

Feces—Undigested food and other waste that is
eliminated through the anus. Also called stools.
Rectum—The lower section of the large intestine, a
digestive system organ. After food has passed
through the stomach and intestines and been
digested, the leftover material, in the form of feces,
enters the rectum, where it stays until defecation.
Suppository—A medicinal substance that slowly
dissolves after being inserted into the rectum (or
other body cavity).

found in fruit and fruit products, tea, and soy).
Herbal teas, ointments, and suppositories, and other
kinds of herbal preparations, are suggested for reducing
discomfort and eliminating hemorrhoids. In particular,
pilewort (Ranunculusficaria), applied in an ointment or
taken as a tea, can reduce the pain of external hemorrhoids. Acupuncture, acupressure, aromatherapy, and
homeopathy are also used to treat hemorrhoids.

Prognosis
Hemorrhoids do not cause cancer and are rarely
dangerous or life threatening. Most clear up after a
few days without professional medical treatment.
However, because colorectal cancer and other digestive system diseases can cause anal bleeding and other
hemorrhoid-like symptoms, people should always
consult a doctor when those symptoms occur.

Prevention
A high-fiber diet and the other lifestyle changes
recommended for coping with existing hemorrhoids
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.

Howard Baker

Henoch-Schönlein purpura see Allergic
purpura
Hepatic carcinoma see Liver cancer,
primary

whereas adults are far likelier to have more severe
symptoms.
Epidemics of HAV infection can infect dozens
and even hundreds (or, on rare occasions, thousands)
of persons. In the public’s mind, outbreaks of hepatitis
A usually are linked with the eating of contaminated
food at a restaurant. It is true that food-handlers, who
may themselves have no symptoms, can start an
alarming, widespread epidemic. Many types of food
can be infected by sewage containing HAV, but shellfish, such as clams and oysters, are common culprits.
Apart from contaminated food and water, certain
groups are at increased risk of getting infectious
hepatitis:


Children at day care centers make up an estimated
14–40% of all cases of HAV infection in the United
States. Changing diapers transmits infection through
fecal-oral contact. Toys and other objects may
remain contaminated for some time. Often a child
without symptoms brings the infection home to siblings and parents.



Troops living under crowded conditions at military
camps or in the field. During World War II there
were an estimated five million cases in German
soldiers and civilians.



Anyone living in heavily populated and squalid conditions, such as the very poor and those placed
in refugee or prisoner-of-war camps.



Homosexual men are increasingly at risk of HAV
infection from oral-anal sexual contact.



Travelers visiting an area where hepatitis A is common are at risk of becoming ill.

Hepatic encephalopathy see Liver
encephalopathy
Hepatitis-associated antigen (HAA) test see
Hepatitis virus tests

Hepatitis A
Definition
Hepatitis A is an inflammation of the liver caused
by a virus, the hepatitis A virus (HAV). It varies in
severity, running an acute course, generally starting
within two to six weeks after contact with the virus,
and lasting no longer than two or three months. HAV
may occur in single cases after contact with an infected
relative or sex partner. Alternately, epidemics may
develop when food or drinking water is contaminated
by the feces of an infected person.

Description
Hepatitis A was previously known as infectious
hepatitis because it spread relatively easily from those
infected to close household contacts. Once the infection ends, there is no lasting, chronic phase of illness.
However it is not uncommon to have a second episode
of symptoms about a month after the first; this is
called a relapse, but it is not clear that the virus persists
when symptoms recur. Both children and adults may
be infected by HAV. Children are the chief victims, but
very often have no more than a flu-like illness or no
symptoms at all (so-called ‘‘subclinical’’ infection),
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The time from exposure to HAV and the onset of
symptoms ranges from two to seven weeks and
averages about a month. The virus is passed in the
feces, especially late during this incubation period,
before symptoms first appear. Infected persons are
most contagious starting a week or so before symptoms develop, and remain so up until the time jaundice
(yellowing of the skin) is noted.
Often the first symptoms to appear are fatigue,
aching all over, nausea, and a loss of appetite. Those
who like drinking coffee and smoking cigarettes may
lose their taste for them. Mild fever is common; it
seldom is higher than 101  F (38.3  C). The liver
often enlarges, causing pain or tenderness in the right
upper part of the abdomen. Jaundice then develops,
typically lasting seven to ten days. Many patients do
1769

Hepatitis A

also help to prevent hemorrhoids. Not straining during bowel movements is essential.

Hepatitis A

KEY TERMS
Antibody—A substance made by the body in
response to a foreign body, such as a virus, which
is able to attack and destroy the invading virus.
Contamination—The process by which an object
or body part becomes exposed to an infectious
agent such as a virus.
Epidemic—A situation where a large number of
infections by a particular agent, such as a virus,
develops in a short time. The agent is rapidly transmitted to many individuals.
Incubation period—The interval from initial exposure to an infectious agent, such as a virus, and the
first symptoms of illness.
Jaundice—Yellowing of the skin (and whites of the
eyes) when pigments normally eliminated by the
liver collect in high amounts in the blood.
Hepatitis A virus magnified 225,000 times. (Custom Medical
Stock Photo. Reproduced by permission.)

not visit the doctor until their skin turns yellow. As
many as three out of four children have no symptoms
of HAV infection, but about 85% of adults will have
symptoms. Besides jaundice, the commonest are
abdominal pain, loss of appetite, and feeling generally
poorly.
Special situations
An occasional patient with hepatitis A will remain
jaundiced for a month, two months or even longer, but
eventually the jaundice will pass. Very rarely, a patient
will develop such severe hepatitis that the liver fails.
HAV infection causes about 100 deaths each year in
the United States. In developed countries, a pregnant
woman who contracts hepatitis A can be expected to do
well although a different form of viral hepatitis (hepatitis E) can cause severe infection in pregnant women.
In developing countries, however, the infection may
prove fatal, probably because nutrition is not adequate.

Diagnosis
The early, flu-like symptoms and jaundice, as well
as rapid recovery, suggest infectious hepatitis without
special tests being done. If there is any question, a
specialist in gastrointestinal disorders or infectious
diseases can confirm the diagnosis—the detection of
a specific antibody, called hepatitis A IgM antibody,
that develops when HAV is present in the body. This
1770

Vaccine—A substance prepared from a weakened
or killed virus which, when injected, helps the
body to form antibodies that will prevent infection
by the natural virus.

test always registers positive when a patient has symptoms, and should continue to register positive for four
to six months. However, hepatitis A IgM antibody will
persist lifelong in the blood and is protective against
reinfection.

Treatment
Once symptoms appear, no antibiotics or other
medicines will shorten the course of infectious hepatitis. Patients should rest in bed as needed, take a
healthy diet, and avoid drinking alcohol and/or any
medications that could further damage the liver. If a
patient feels well it is all right to return to school or
work even if some jaundice remains.

Prognosis
Most patients with acute hepatitis, even when
severe, begin feeling better in two to three weeks, and
recover completely in four to eight weeks. After recovering from hepatitis A, a person no longer carries the
virus and remains immune for life. In the United
States, serious complications are infrequent and
deaths are very rare. In the United States, as many as
75% of adults over 50 years of age will have blood test
evidence of previous hepatitis A.
GALE ENCYCLOPEDIA OF MEDICINE

The single best way to keep from spreading hepatitis A infection is to wash the hands carefully after
using the toilet. Those who are infected should not
share items that might carry infection. Special care
should be taken to avoid transmitting infection to a
sex partner. Travelers should avoid water and ice if
unsure of their purity, or they can boil water for one
minute before drinking it. All foods eaten should be
packaged, well cooked or, in the case of fresh fruit,
peeled.
If exposure is a possibility, infection may be prevented by an injection of a serum fraction containing
antibody against HAV. This material, called immune
serum globulin (ISG), is 90% protective even when
injected after exposure—providing it is given within
two weeks. Anyone living with an infected patient
should receive ISG. For long-term protection, a killed
virus hepatitis A vaccine became available in 1995.
More than 95% of those vaccinated will develop an
adequate amount of anti-HAV antibody. Those who
should consider being vaccinated include healthcare
professionals, those working at day care and similar
facilities, frequent travelers to areas with poor sanitation, those with any form of chronic liver disease,
and those who are very sexually active. Starting in
2000, routine immunization with the hepatitis A
vaccine was recommended for children born in states
where the rate of hepatitis A was two or more times
the national average (Alaska, Arizona, California,
Idaho, Nevada, New Mexico, Oklahoma, Oregon,
South Dakota, Utah, and Washington) and suggested in states where the rate was 1.5 times the
national average (Arkansas, Colorado, Missouri,
Montana, Texas and Wyoming).
Larry I. Lutwick, MD



an increase in the blood to the affected organ



redness and swelling of the organ



influx of immune agents like white blood cells and
their arsenal of chemical weapons



pain

As the acute process subsides, there is either healing or lingering activity. Lingering activity—chronic
disease—has a milder presentation with similar ingredients. Healing often takes the form of scarring,
wherein normal functioning tissue is replaced by
tough, fibrous, and non-productive scar. Both chronic
disease and healing can happen simultaneously, so
that scar tissue progressively replaces normal tissue.
This leads to cirrhosis, a liver so scarred it is unable to
do its job adequately.
Alcohol can cause either an acute or a chronic
disease in the liver. The acute disease can be severe,
even fatal, and can bring with it hemolysis–blood cell
destruction. Alcohol can also cause a third type of
liver disease, fatty liver, in which the continuous
action of alcohol turns the liver to useless fat. This
condition eventually progresses to cirrhosis if the
poisoning continues.

Causes and symptoms
Inflammation of the liver can be caused by a great
variety of agents—poisons, drugs, viruses, bacteria,
protozoa, and even larger organisms like worms.
Alcohol is a poison if taken in more than modest
amounts. It favors destroying stomach lining, liver,
heart muscle, and brain tissue. The liver is a primary
target because alcohol travels to the liver after leaving
the intestines. Those who drink enough to get alcohol
poisoning have a tendency to be undernourished, since
alcohol provides ample calories but little nutrition. It is
suspected that both the alcohol and the poor nutrition
produce alcoholic hepatitis.

Diagnosis

Hepatitis, alcoholic
Definition
Alcoholic hepatitis is an inflammation of the liver
caused by alcohol.

Hepatitis of all kinds causes notable discomfort,
loss of appetite, nausea, pain in the liver, and usually
jaundice (turning yellow). Blood test abnormalities are
unmistakably those of hepatitis, but selecting from
so many the precise cause may take additional diagnostic work.

Description
Irritation, be it from toxins or infections, causes a
similar response in body organs. The response is
known as inflammation and consists of:
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
As with all poisonings, removal of the offending
agent is primary. There is no specific treatment for
1771

Hepatitis, alcoholic

Prevention

Hepatitis, autoimmune

Description

KEY TERMS
Cirrhosis—Disruption of normal liver structure and
function caused by any type of chronic disease
such as hepatitis and alcohol abuse.
Fatty liver—An abnormal amount of fat tissue in
the liver caused by alcohol abuse.
Hemolysis—Disintegration of read blood cells.
Protozoa—One celled microscopic organisms like
amoeba.

alcohol poisoning. General supportive measures must
see the patient through until the liver has healed by
itself. In the case of fulminant (sudden and severe)
disease, the liver may be completely destroyed and
have to be replaced by a transplant.

Prognosis
The liver is robust. It can heal without scarring
after one or a few episodes of hepatitis that resolve
without lingering. It can, moreover, regrow from a
fragment of its former self, provided there is not disease or poison still inhibiting it.

Prevention
Alcohol is lethal in many ways when ingested in
excess. Research suggests that the maximum healthy
dose of alcohol per day is roughly one pure ounce—
the amount in two cocktails, two glasses of wine, or
two beers.
Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
Local chapters of Alcoholics Anonymous.

J. Ricker Polsdorfer, MD

Hepatitis, autoimmune
Definition
A form of liver inflammation in which the body’s
immune system attacks liver cells.
1772

Autoimmunity causes the body’s defense mechanisms to turn against itself. Many of the tissues in the
body can be the target of such an attack. While one
tissue type predominates, others may be involved in a
general misdirection of immune activity, perhaps
because the specific target antigen is present in differing
quantities in each of the affected tissues. There seem to
be hereditary causes for autoimmunity, since these diseases tend to run in families and have genetic markers.
Among the more common diseases believed to fall
within this category are rheumatoid arthritis, systemic
lupus erythematosus, multiple sclerosis, and psoriasis.
The process of autoimmune disease is very similar
to infectious disease and allergy, so that great caution
is observed in placing a disorder in this class. Germs
were found to cause several diseases originally thought
to be autoimmune. Allergens cause others. Many
more may be uncovered. Autoimmunity is often
believed to originate with a virus infection. A chemical
in the virus resembles a body chemical so closely that
the immune system attacks both.
Autoimmune hepatitis is similiar to viral hepatitis,
a disease of the liver. It can be an acute disease that
kills over a third of its victims within six months, it can
persist for years, or it can return periodically. Some
patients develop cirrhosis of the liver which, over time,
causes the liver to cease functioning.

Causes and symptoms
Symptoms of autoimmune hepatitis resemble
those of other types of hepatitis. Patients who develop
autoimmune hepatitis experience pain under the right
ribs, fatigue and general discomfort, loss of appetite,
nausea, sometimes vomiting and jaundice. In addition,
other parts of the body may be involved and contribute their own symptoms.

Diagnosis
Extensive laboratory testing may be required to
differentiate this disease from viral hepatitis. The distinction may not even be made during the initial episode. There are certain markers of autoimmune
disease in the blood that can lead to the correct diagnosis if they are sought. In advanced or chronic cases a
liver biopsy may be necessary.

Treatment
Autoimmune hepatitis is among the few types
of hepatitis that can be treated effectively. Since treatment itself introduces problems in at least 20%
GALE ENCYCLOPEDIA OF MEDICINE

Allergen—Any chemical that causes an immune
reaction only in people sensitive to it.
Antigen—Any chemical that can be the target of an
immune response.
Biopsy—Surgical removal of a piece of tissue for
examination.
Jaundice—A yellow color to the skin from bile that
backs up into the circulation.

of patients, it is reserved for the more severe
cases. Up to 80% of patients improve with cortisone
treatment, although a cure is unlikely. Another
drug—azathioprine—is sometimes used concurrently.
Treatment continues for over a year and may be
restarted during a relapse. At least half the patients
relapse at some point, and most will still continue to
have progressive liver scarring.
If the liver fails, transplant is the only recourse.

Prognosis
In spite of treatment autoimmune hepatitis can
re-erupt at any time, and may continue to damage
and scar the liver. The rate of progression varies
considerably from patient to patient.
Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.

J. Ricker Polsdorfer, MD

Hepatitis B
Definition
Hepatitis B is a potentially serious form of liver
inflammation due to infection by the hepatitis B virus
(HBV). It occurs in both rapidly developing (acute)
and long-lasting (chronic) forms, and is one of the
most common chronic infectious diseases worldwide.
An effective vaccine is available that will prevent the
disease in those who are later exposed.
GALE ENCYCLOPEDIA OF MEDICINE

Commonly called ‘‘serum hepatitis,’’ hepatitis B
ranges from mild to severe. Some people who are
infected by HBV develop no symptoms and are totally
unaware of the fact, but they may carry HBV in their
blood and pass the infection on to others. In its
chronic form, HBV infection may destroy the liver
through a scarring process, called cirrhosis, or it may
lead to cancer of the liver.
When a person is infected by HBV, the virus
enters the bloodstream and body fluids, and is able
to pass through tiny breaks in the skin, mouth, or the
male or female genital area. There are several ways of
getting the infection:


During birth, a mother with hepatitis B may pass
HBV on to her infant.



Contact with infected blood is a common means of
transmitting hepatitis B. One way this may happen is
by being stuck with a needle. Both health care workers and those who inject drugs into their veins are at
risk in this way.



Having sex with a person infected by HBV is an
important risk factor (especially anal sex).

Although there are many ways of passing on
HBV, the virus actually is not very easily transmitted.
There is no need to worry that casual contact, such as
shaking hands, will expose one to hepatitis B. There is
no reason not to share a workplace or even a restroom
with an infected person.
More than 300 million persons throughout the
world are infected by HBV. While most who become
chronic carriers of the virus live in Asia and Africa,
there are no fewer than 1.5 million carriers in the
United States. Because carriers represent a constant
threat of transmitting the infection, the risk of hepatitis B is always highest where there are many carriers.
Such areas are said to be endemic for hepatitis B.
When infants or young children living in an endemic
area are infected, their chance of becoming a chronic
hepatitis B carrier is at least 90%. This probably is
because their bodies are not able to make the substances (antibodies) that destroy the virus. In contrast,
no more than 5% of infected teenagers and adults
develop chronic infection.

Causes and symptoms
With the exception of HBV, all the common
viruses that cause hepatitis are known as RNA viruses
because they contain ribonucleic acid or RNA as their
genetic material. HBV is the only deoxyribonucleic
1773

Hepatitis B

Description

KEY TERMS

Hepatitis B

acid or DNA virus that is a major cause of hepatitis.
HBV is made up of several fragments, called antigens,
that stimulate the body’s immune system to produce
the antibodies that can neutralize or even destroy the
infecting virus. It is, in fact, the immune reaction, not
the virus, that seems to cause the liver inflammation.
Acute hepatitis B
In the United States, a majority of acute HBV
infections occur in teenagers and young adults. Half
of these youth never develop symptoms, and only
about 20%—or one in five infected patients—develop
severe symptoms and yellowing of the skin ( jaundice).
Jaundice occurs when the infected liver is unable to get
rid of certain colored substances, or pigments, as it
normally does. The remaining 30% of patients have
only ‘‘flu-like’’ symptoms and will probably not even
be diagnosed as having hepatitis unless certain tests
are done.
The most commom symptoms of acute hepatitis B
are loss of appetite, nausea, generally feeling poorly,
and pain or tenderness in the right upper part of the
abdomen (where the liver is located). Compared to
patients with hepatitis A or C, those with HBV infection are less able to continue their usual activities and
require more time resting in bed.
Occasionally patients with HBV infection will
develop joint swelling and pain (arthritis) as well as
hives or a skin rash before jaundice appears. The joint
symptoms usually last no longer than three to seven days.
Typically the symptoms of acute hepatitis B do
not persist longer than two or three months. If they
continue for four months, the patient has an abnormally long-lasting acute infection. In a small number
of patients—probably fewer than 3%—the infection
keeps getting worse as the liver cells die off. Jaundice
deepens, and patients may bleed easily when the levels
of coagulation factors (normally made by the liver)
decrease. Large amounts of fluid collect in the abdomen and beneath the skin (edema). The least common
outcome of acute HBV infection, seen in fewer than
1% of patients, is fulminant hepatitis, when the liver
fails entirely. Only about half of these patients can be
expected to live.
Chronic hepatitis B
HBV infection lasting longer than six months is
said to be chronic. After this time it is much less likely
for the infection to disappear. Not all carriers of the
virus develop chronic liver disease; in fact, a majority
have no symptoms. But, about one in every four HBV
carriers develop liver disease that gets worse over time,
1774

as the liver becomes more and more scarred and less
able to carry out its normal functions. A badly scarred
liver is called cirrhosis. Patients are likely to have an
enlarged liver and spleen, as well as tiny clusters of
abnormal blood vessels in the skin that resemble
spiders.
The most serious complication of chronic HBV
infection is liver cancer. Worldwide this is the most
common cancer to occur in men. Nevertheless, the
overall chance that liver cancer will develop at any
time in a patient’s life is probably much lower than
10%. Patients with chronic hepatitis B who drink or
smoke are more likely to develop liver cancer. It is not
unusual for a person to simultaneously have both
HBV infection and infection by HIV (human immunodeficiency virus, the cause of AIDS). A study released
in 2003 reported that men infected with both HIV and
HBV were more likely to die from liver disease than
people infected with just one of the diseases.

Diagnosis
Hepatitis B is diagnosed by detecting one of the
viral antigens—called hepatitis B surface antigen
(HBsAg)—in the blood. Later in the acute disease,
HBsAg may no longer be present, in which case a
test for antibodies to a different antigen—hepatitis B
core antigen—is used. If HBsAg can be detected in the
blood for longer than six months, chronic hepatitis B
is diagnosed. A number of tests can be done to learn
how well, or poorly, the liver is working. They include
blood clotting tests and tests for enzymes that are
found in abnormally high amounts when any form of
hepatitis is present.

Treatment
In the past, there was no treatment available for
hepatitis B. But developments have been made in
recent years on drugs that suppress the virus and its
symptoms. In early 2003, a drug called adefovir was
reported as an effective treatment. Another drug
called tenofovir was demonstrated as effective in
patients infected with both hepatitis B and HIV. Two
studies also reported on the effectiveness of a drug
called Preveon, which was more expensive than others.
Patients also should rest in bed as needed, continue to
eat a healthy diet, and avoid alcohol. Any non-critical
surgery should be postponed.

Prognosis
Each year an estimated 150,000 persons in the
United States get hepatitis B. More than 10,000 will
GALE ENCYCLOPEDIA OF MEDICINE

Hepatitis B

Double-Stranded DNA

Single-Stranded DNA
HBcAg
Polymerase
HBsAg

HBeAg

Hepatitis B virus (HBV) is composed of an inner protein core and an outer protein capsule. The outer capsule contains
the hepatitis B surface antigen (HBsAg). The inner core contains HBV core antigen (HBcAg) and hepatitis B e-antigen
(HBeAg). This cell also contains polymerase, which catalyzes the formation of the cell’s DNA. HBV is the only hepatitis-causing
virus that has DNA, instead of RNA. (Illustration by Electronic Illustrators Group.)

require hospital care, and as many as 5,000 will die
from complications of the infection. About 90% of all
those infected will have acute disease only. A large
majority of these patients will recover within three
months. It is the remaining 10%, with chronic infection, who account for most serious complications and
deaths from HBV infection. In the United States,
perhaps only 2% of all those who are infected will
become chronically ill. The course of chronic HBV
infection in any particular patient is unpredictable.
Some patients who do well at first may later develop
serious complications. Even when no symptoms of
liver disease develop, chronic carriers remain a threat
to others by serving as a source of infection.

KEY TERMS
Antibody—A substance formed in the body in
response to a foreign body, such as a virus, which
can then attack and destroy the invading virus.
Antigen—Part of an invading microorganism, such
as a virus, that causes tissue damage (in hepatitis, to
the liver), and that also stimulates the body’s
immune system to produce antibodies.
Cirrhosis—The end result of many forms of liver
disease, the condition of the liver when its cells
have been damaged or destroyed and are replaced
by scar tissue.
Vaccine—A substance prepared from a weakened
or killed virus which, when injected, helps the
body to form antibodies that will attack an invading
virus and may prevent infection altogether.

Prevention
The best way to prevent any form of viral hepatitis
is to avoid contact with blood and other body fluids of
infected individuals. The use of condoms during sex
also is advisable.
If a person is exposed to hepatitis B, a serum
preparation containing a high level of antibody
against HBV may prevent infection if given within
three to seven days of exposure. Babies born of a
mother with HBV should receive the vaccine within
24 hours. An effective and safe vaccine is available that
reliably prevents hepatitis B. Vaccination is suggested
for most infants and for children aged 10 and younger
whose parents are from a place where hepatitis B is
GALE ENCYCLOPEDIA OF MEDICINE

common. Teenagers not vaccinated as children and all
adults at risk of exposure also should be vaccinated
against hepatitis B. Three doses are recommended.
Those at increased risk of getting hepatitis B, and
who therefore should be vaccinated, include:


household contacts of a person carrying HBV



healthcare workers who often come in contact with
patients’ blood or other body fluids
1775

Hepatitis C



patients with kidney disease who periodically
undergo hemodialysis



homosexual men who are sexually active, and heterosexuals who have multiple sex partners



persons coming from areas where HBV infection is a
major problem



prisoners and others living in crowded institutions



drug abusers who use needles to inject drugs into
their veins

Studies released in 2003 showed increased risk of
nonresponse to hepatitis B vaccines among adults over
age 30. This may be related to age-associated changes
in the immune system.
Resources
PERIODICALS

‘‘Antiviral Effective Against Hepatitis B Virus in HIVcoinfected.’’ Virus Weekly January 28, 2003: 16.
Bauer, Jeff. ‘‘Co-infection with Hepatitis B and HIV
Increases Men’s Risks of Death from Liver Disease.’’
RN March 2003: 97.
Elliott, William T. ‘‘Warfarin Effectively Prevents Venous
Thromboembolism (Pharmacology Watch).’’ Critical
Care Alert April 2003.
‘‘Hepatitis B Vaccine Loses Effectiveness in Older Adults.’’
Vaccine Weekly January 29, 2003: 23.
ORGANIZATIONS

Hepatitis B Foundation. 101 Greenwood Ave., Suite 570,
Jenkintown, PA 19046. (215) 884-8786.
<info@hepb.org>.

Description
HCV is a blood-borne virus that is and always was
the major cause of ‘‘transfusion hepatitis,’’ which can
develop in patients who are given blood or most blood
products except for gamma-globulin. The existence
of a third hepatitis virus (besides the A and B viruses)
became clear in 1974, but HCV was first identified
in 1989. Thereafter, tests were devised to detect the
virus in blood units before transfusing them. As a
result, since the early 1990s transfused blood is less
commonly the cause of hepatitis C.
The hepatitis C form of hepatitis is generally mild
in its early, acute stage, but it is much likelier than
hepatitis B (85% as compared to 10%) to produce
chronic liver disease. Therefore, more than two of
every three persons who are infected by HCV may
continue to have the virus in their blood and so become
carriers, who can transmit the infection to others.
The most common way of transmitting hepatitis
C is when blood containing the virus enters another
person’s circulation through a break in the skin or
the mucosa (inner lining) of the mouth or genitals.
HCV also can be passed (although uncommonly)
from an infected mother to the infant she is carrying.
(The risk of infection from breast milk is very low.)
Also, HCV can be rarely spread through sexual intercourse. Usually, however, the sexual contacts of
chronic carriers of hepatitis C are not infected.
Those at increased risk of developing hepatitis C
include:


healthcare workers who come in contact with infected
blood from a cut or bruise, or from a device or
instrument that has been infected (‘‘contaminated’’)



persons who inject illicit drugs into their veins and
skin, especially if they share needles and syringes
with other users



anyone who gets a tattoo or has his or her skin
pierced with an infected needle



persons with hemophilia (who because they bleed
very easily may require large amounts of blood and
blood products over time)



patients with kidney disease who have periodic
dialysis—a treatment that rids their blood of toxic
substances—and often requires the patient to have
blood transfusions

David A. Cramer, MD
Teresa G. Odle

Hepatitis C
Definition
Hepatitis C is a form of liver inflammation that
causes primarily a long-lasting (chronic) disease.
Acute (newly developed) hepatitis C is rarely observed
as the early disease is generally quite mild. Spread
mainly by contact with infected blood, the hepatitis
C virus (HCV) causes most cases of viral liver infection
not due to the A and B hepatitis viruses. In fact, before
other viral types were found, hepatitis C was referred
to as ‘‘non-A, non-B hepatitis.’’ It is not a new infection, just newly diagnosable and has been widely present in the U.S. population for decades.
1776

About one-fourth of patients with hepatitis C do
not belong to any of these high-risk groups. Although
blood transfusion is a much less common cause of HCV
infection than in earlier years, cases still occur. Also,
sexual transmission is possible, and may take place
with either heterosexual or homosexual behavior.
GALE ENCYCLOPEDIA OF MEDICINE

More than half of all patients who develop hepatitis C have no symptoms or signs of liver disease.
Some, however, may have a minor illness with flulike symptoms. Any form of hepatitis may keep the
liver from eliminating certain colored (pigmented)
substances as it normally does. These pigments collect
in the skin, turning it yellow, and also may cause
yellowing of the whites of the eyes. About one in
four patients with hepatitis C will develop this yellowing of the skin called jaundice (or yellow jaundice).
Some patients lose their appetite and frequently feel
tired. Patients may also feel nauseous or even vomit.
In most patients, HCV can still be found in
the blood six months after the start of acute infection,
and these patients are considered to be carriers. If the
virus persists for one year, it is very unlikely to disappear. About 20% of chronic carriers develop cirrhosis (scarring) of the liver when the virus damages or
destroys large numbers of liver cells, which are then
replaced by scar tissue. Cirrhosis may develop only
after a long period of time (as long as 20 years) and
often even more has passed. Most (four in five)
patients will not develop cirrhosis and instead have
a mild, chronic form of infection called chronic persistent hepatitis and when they die, will die with, not of,
the infection.
Patients with chronic HCV infection are at risk of
developing certain very serious complications:


Patients with hepatitis C who develop cirrhosis may
go on to have liver cancer—called hepatocellular
carcinoma. Patients with liver cancer have an average life expectancy measured in months unless the
tumor is totally removed.



Patients also are at risk of developing a combination
of joint pain, weakness, and areas of bleeding into the
skin. The kidneys and brain also may be affected.
Perhaps 5% of patients with chronic HCV infection
develop this condition, called cryoglobulinemia.



Patients with porphyria (metabolic disturbances
characterized by extreme sensitivity to light) develop
blisters in areas of their skin that are exposed to
sunlight. The skin also may be easily bruised, and,
in time, can become discolored.

Diagnosis
Hepatitis C should be suspected if a patient develops jaundice and reports recent contact with the blood
of a person who may have been infected. There is a
blood test to detect HCV IgG antibody, a substance
that the body makes to combat HCV. Care is required,
GALE ENCYCLOPEDIA OF MEDICINE

as the test often does not show positive for up to two
to three months after infection. Also, the test only
shows whether a person has ever been infected by
HCV, not whether the virus is still present. A less
available and more expensive test measuring HCV
RNA (the viral gene) can be found in early infection
before the antibody is measurable. Simpler blood tests
can be done to show how much jaundice-causing pigment is in a patient’s blood, or to measure the levels of
certain proteins made by the liver. High levels of these
‘‘liver enzymes’’ (called ALT and AST) indicate that
the liver is inflamed. Rising levels could suggest that
the infection is getting worse.

Treatment
Patients who fail to recover promptly may be
advised to see a specialist in gastrointestinal disorders
(which include liver disease) or infectious diseases.
A balanced diet with little fat is best, and patients
should limit their alcohol intake, or, better, avoid alcohol altogether. Any medication that can cause liver
damage should be avoided. The amount of time in
bed depends on how poorly a particular patient feels.
A natural body protein, interferon alpha, now can
be made in large amounts by genetic engineering, and
improves the outlook for many patients who have
chronic hepatitis C. The protein can lessen the symptoms of infection and improve liver function. Not all
patients respond, however, and others get less benefit
the longer they take interferon. Fever and flu-like
symptoms are frequent side effects of this treatment.
Using a high dose for six months, nearly half of
patients have responded positively. Half the patients
who do respond well will relapse after the drug is
stopped. A newer medication called ribavirin is now
commonly used with interferon and, if tolerated, does
increase response rates. A newer form of interferon,
called pegylated interferon, is also being used for treatment. Because of the problems with treatment, many
people have sought alternative medications such as
milk thistle or certain Asian herbs.
When hepatitis destroys most or all of the liver,
the only hope may be a liver transplant. Unfortunately
the new liver usually becomes infected by HCV. On the
other hand, total liver failure is less frequent than in
patients with hepatitis B.

Prognosis
In roughly one-fifth of patients who develop hepatitis C, the acute infection will subside, and they will
recover completely within four to eight weeks and
1777

Hepatitis C

Causes and symptoms

Hepatitis D



The sharing of personal items should be avoided,
particularly those that can puncture the skin or inside
of the mouth, such as razors, nail files and scissors,
and even toothbrushes.



Condoms should be used for either vaginal or
oral sex.

KEY TERMS
Antibody—A substance formed in the body in
response to a foreign body, such as a virus, which
can attack and destroy the invading foreign body or
virus.
Carrier—A person who, after recovering from a
viral infection, continues to ‘‘carry’’ the virus in
the blood and can pass it on to others who then
may develop infection.
Contamination—Passage of an infectious organism, such as a virus, from an infected person to an
object such as a needle, which then, when used,
may pass infection to another person.
Hepatocellular carcinoma—A dangerous cancer
of the liver that may develop in patients who have
had hepatitis, sometimes as long as 20 or 30 years
earlier.

If a person does develop hepatitis C, its spread
may be prevented by:


not donating blood



not sharing personal items with others



wiping up any spilled blood while using gloves,
household bleach, and disposable paper towels



carefully covering any cut or wound with a bandaid
or dressing



practicing safe sex, especially during the acute phase
of the infection
Larry I. Lutwick, MD

Porphyria—Any of a group of disturbances of porphyrin metabolism characterized by excess
pophyrins (various biologically active compounds
with a distinct structure) in the urine and by
extreme sensitivity to light.

Hepatitis D
Definition
have no later problems. Other patients face two risks:
they themselves may develop chronic liver infection
and possibly serious complications such as liver cancer,
and, also, they will continue carrying the virus and may
pass it on to others. The overall risk of developing
cirrhosis, or liver scarring, is about 15% of all patients
infected by HCV. Acute liver failure is less frequent
in patients with chronic hepatitis C than in those with
other forms of hepatitis.

Prevention
No vaccine has yet been developed to prevent
hepatitis C in persons exposed to the virus. In addition, there is no role of gamma-globulin in the prevention of the infection. There are, however, many ways
in which infection may be avoided:


Those who inject drugs should never share needles,
syringes, swabs, spoons, or anything else that comes
in contact with bodily fluids. They should always use
clean equipment.



Hands should be washed before and after contact
with another person’s blood or if the skin is
penetrated.

1778

Hepatitis D (or delta, the Greek letter ‘‘D’’), is a
form of liver inflammation that occurs only in patients
who also are infected by the hepatitis B virus. Infection
by the hepatitis delta virus (HDV) either occurs at the
same time as hepatitis B develops, or develops later
when infection by hepatitis B virus (HBV) has entered
the chronic (long-lasting) stage.

Description
Delta hepatitis can be quite severe, but it is seen
only in patients already infected by HBV. In the late
1970s, Italian physicians discovered that some patients
with hepatitis B had another type of infectious agent
in their liver cells. Later the new virus—HDV—was
confirmed by experimentally infecting chimpanzees.
When both viruses are present, acute infection tends
to be more severe. Furthermore, patients with both
infections are likelier than those with HBV alone to
develop chronic liver disease, and, when it occurs, it is
more severe.
About 300 million persons worldwide carry HBV.
Of them, at least 5% probably also have delta hepatitis. In North America HDV infection appears to be
less frequent: 4% of all patients with acute hepatitis B
GALE ENCYCLOPEDIA OF MEDICINE

Certain individuals—the same ones who are at
increased risk of developing hepatitis B—are the
prime candidates to be infected by HDV. For example:


Not infrequently, HDV infection occurs in patients
with chronic HBV infection who also have hemophilia, a bleeding disease. These patients are at risk
because they require large amounts of transfused
blood and blood products that may contain HDV.



In some areas, one-fourth to one-half of patients
with chronic HBV infection who inject themselves
with illicit drugs become infected by HDV as well.
Drug abusers who share contaminated needles are
likely to infect one another.



Patients who get HBV infection by sexual contact
may also be infected by HDV, although the delta
virus is less often spread in this way than is HBV
itself. Between 10–25% of homosexual men with
chronic HBV infection harbor the delta virus.



Like hepatitis B, HDV infection may develop in healthcare workers who are victims of a needle stick, and it
also can be spread within households when personal
items such as a razor or toothbrush are shared.

Causes and symptoms
The delta virus is a small and incomplete viral
particle. Perhaps this is why it cannot cause infection
on its own. Its companion virus, HBV, actually forms
a covering over the HDV particle. In chronically ill
patients (those whose virus persists longer than six
months), the combined viruses cause inflammation
throughout the liver and eventually destroy the liver
cells, which are then replaced by scar tissue. This
scarring is called cirrhosis.
When HBV and HDV infections develop at the
same time, a condition called coinfection, recovery is
the rule. Only 2–5% of patients become chronic carriers (have the virus remain in their blood more than
six months after infection). It may be that HDV actually keeps HBV from reproducing as rapidly as it
would if it were alone, so chronic infection is less likely.
When HBV infection occurs first and is followed by
HDV infection, the condition is called superinfection.
This is a more serious situation. Between half and
GALE ENCYCLOPEDIA OF MEDICINE

two-thirds of patients with superinfection develop
severe acute hepatitis. Once the liver cells contain large
numbers of HBV viruses, HDV tends to reproduce
more actively. Massive infection and liver failure are
more common in superinfection. The risk of liver cancer, however, is no greater than from hepatitis B alone.
As with other forms of hepatitis, the earliest symptoms are nausea, loss of appetite, joint pains, and
tiredness. There may be fever (not marked) and an
enlarged liver may cause discomfort or actual pain in
the right upper part of the abdomen. Later, jaundice
(a yellowing of the skin and whites of the eyes that
occurs when the liver is no longer able to eliminate
certain pigmented substances) may develop.

Diagnosis
HDV infection may be diagnosed by detecting the
antibody against the virus. Unfortunately this test
cannot detect acute coinfection or superinfection as
early as when symptoms first develop. Antibody
against HDV usually is found no sooner than 30
days after symptoms appear. Until recently, the virus
itself could only be identified by testing a small sample
of liver tissue. Scientists now are developing a blood
test for HDV that should make diagnosis faster and
easier. When HDV is present, liver enzymes (proteins
made by the liver) are present in abnormally high
amounts. In some patients with coinfection, the
enzyme levels peak twice, once when HBV infection
starts and again at the time of HDV infection.

Treatment
As in any form of hepatitis, patients in the acute
stage should rest in bed as needed, eat a balanced diet,
and avoid alcohol. Alpha-interferon, the natural body
substance which helps control hepatitis C, has generally not been found helpful in treating hepatitis D. If
the liver is largely destroyed and has stopped functioning, liver transplantation is an option. Even when the
procedure is successful, disease often recurs and cirrhosis may actually develop more rapidly than before.

Prognosis
A large majority of patients with coinfection of
HBV and HDV recover from an episode of acute
hepatitis. However, about two-thirds of patients
chronically infected by HDV go on to develop cirrhosis of the liver. In one long-term study, just over half of
patients who became carriers of HDV had moderate
or severe liver disease, and one-fourth of them died.
If very severe liver failure develops, the chance of
1779

Hepatitis D

have HDV infection. The delta virus causes an estimated 2% of all cases of acute viral hepatitis in the
United States. The rate of HDV infection varies widely
in different parts of the world; it is a very serious
infection in some countries and quite mild in others.
Chronic delta hepatitis is a more serious disease than
either chronic hepatitis B alone or hepatitis C.

Hepatitis, drug-induced

KEY TERMS
Alpha-interferon—A natural body substance that
now can be made in large quantities and is an
effective treatment for some types of viral inflammatory disease, including hepatitis C.
Antibody—A substance formed in the body in
response to an invading microorganism, such as a
virus, which can attack and destroy the invading
virus.
Coinfection—Invasion of the body by two viruses
at about the same time.
Hemophilia—A bleeding disease that may call for
the transfusion of large amounts of blood and blood
products.
Superinfection—Infection by a second virus after a
previous infection by a different virus has become
well established.

a patient surviving is no better than 50%. A liver
transplant may improve this figure to 70%. When
transplantation is done for cirrhosis, rather than for
liver failure, nearly 90% of patients live five years or
longer. The major concern with transplantation is
infection of the transplanted liver; this may occur in
as many as 40% of transplant patients.
When a child with viral hepatitis develops cirrhosis,
HDV infection is commonly responsible. A woman who
develops delta hepatitis while pregnant will do as well
as if she were not pregnant; and there is no increased
risk that the newborn will be malformed in any way.

Prevention
The vaccine against hepatitis B also prevents delta
hepatitis, since it cannot occur unless HBV infection is
present. Hopefully, a vaccine can be developed that
will keep delta infection from developing in chronic
HBV carriers. However, if a person already has HBV
infection, any exposure to blood should be strictly
avoided. A high level of sexual activity with multiple
partners is also a risk factor for delta hepatitis.
Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.

David A. Cramer, MD
1780

Hepatitis, drug-induced
Definition
Inflammation of the liver due to an adverse reaction with a drug.

Description
The liver is a very important organ to the body.
It is a large internal organ weighing more than three
pounds in the average adult. It performs over 100
functions including formation of bile, detoxification
of harmful substances, vitamin storage and metabolism of carbohydrates, fats and proteins. Serious
complications could arise when the liver becomes
inflamed due to hepatitis when it is not able to perform
these tasks. A virus most often causes hepatitis but
certain drugs can also induce it.
Drug-induced hepatitis (also called toxic hepatitis) occurs in eight in every 10,000 people because
the liver reacts abnormally during drug exposure,
leading to liver damage. This pathology causes the
liver not to function properly and the symptoms can
begin to be seen. Women tend to be affected almost
twice as often as men. Older people are more prone
to this type of hepatitis because their bodies aren’t able
to repair themselves as fast as younger people. Drugs
that can be associated with drug-induced hepatitis
include acetaminophen, vitamin A, and PTU (a drug
treatment for tuberculosis).

Causes and symptoms
There are three general types of drug-induced
hepatitis: toxic, metabolic idiosyncrasy and immunologic idiosyncrasy. With toxic hepatitis liver damage
as the result of a drug complication with hepatotoxins happens to everyone who takes that particular
drug. On the other hand, hepatitis resulting from
a metabolic or immunologic idiosyncrasy only happens to certain people, those predisposed to particular idiosyncrasy.
In patients with a metabolic idiosyncrasy the
person metabolizes the drug differently than most
people causing a harmful by-product that damages
the liver. A metabolic idiosyncrasy is seen in 0.1-2%
of people and it is complicated by use of alcohol.
With an immunologic idiosyncrasy the patient’s
body recognizes the metabolized drug by-products as
foreign. This leads to the destruction of liver cells
containing the by-product via the immune system
GALE ENCYCLOPEDIA OF MEDICINE

Hepatitis—General inflammation of the liver.
Hepatomegaly—General swelling of the liver.
Hepatotoxin—A substance that is toxic to the liver.
Idiosyncrasy—A defect in that particular pathway
resulting in an abnormality.

resulting in hepatitis. An immunologic idiosyncrasy is
seen in less than one person per 10,000 (0.01%) people
and is more than twice as common in women.
The symptoms of drug-induced hepatitis are similar to viral hepatitis. Drug induced hepatitis tends to
be acute. If it is not caught soon enough the damage
could be permanent resulting in chronic hepatitis.
Some of the common symptoms are:


nausea



vomiting



headache



anorexia



jaundice



clay color stools



dark urine



hepatomegaly

If there is a history of liver damage certain medications should not be taken. Doctors will be familiar
with these.
Resources
BOOKS

Feldman, Sleisenger, and Scharschmidt. ‘‘Liver
Diseases Caused by Drugs, Anesthetics, and
Toxins.’’ In Gastrointestinal and Liver Disease.
Philadelphia: W.B. Saunders Company, 2001,
pp.1232-1237.
Holmes, Nancy H. ‘‘Hepatobiliary Disorders.’’ In Diseases.
Pennsylvania: Springhouse Corporation, 2001,
pp.744-53.
PERIODICALS

Hautekeete, Horsmans, Van Waeyenberge, Demanet,
Henrion, Verbist, Brenard, Sempoux, Michielsen,
Yap, Rahier, and Geubel. ‘‘HLA Association of
Amoxicillin-Clavulanate—Induced Hepatitis.’’
Gastroenterology November 1999: 1181-86.

Thomas Scott Eagan
Ronald Watson, PhD

Hepatitis E
Definition

Diagnosis
Diagnosis is typically made through a physical
exam along with a patient history to identify any
possible hepatotoxins. Blood tests are usually done
as well. An increased white blood cell count is typical.

Treatment
There isn’t any specific treatment other than
immediate discontinuance of the causative agent.
Rest during the acute phase of the disease is vital
along with the intake of fluids to maintain hydration.

Prognosis
Usually the symptoms will go away after the drug
has been eliminated due to the liver repairing itself.
A full recovery is typically expected unless it wasn’t
treated quickly resulting in more liver damage being
done than normal.
GALE ENCYCLOPEDIA OF MEDICINE

The hepatitis E virus (HEV) is a common cause
of hepatitis that is transmitted via the intestinal tract,
and is not caused by the hepatitis A virus. Spread most
often by contaminated drinking water, HEV infection
occurs mainly in developing countries.

Description
Hepatitis E is also known as epidemic non-A,
non-B hepatitis. Like hepatitis A, it is an acute and
short-lived illness that can sometimes cause liver
failure. HEV, discovered in 1987, is spread by the
fecal-oral route. It is constantly present (endemic) in
countries where human waste is allowed to get into
drinking water without first being purified. Large
outbreaks (epidemics) have occurred in Asian and
South American countries where there is poor sanitation. In the United States and Canada no outbreaks
have been reported, but persons traveling to an
endemic region may return with HEV.
1781

Hepatitis E

Prevention

KEY TERMS

Hepatitis E

Causes and symptoms
There are at least two strains of HEV, one found
in Asia and another in Mexico. The virus may start
dividing in the gastrointestinal tract, but it grows
mostly in the liver. After an incubation period (the
time from when a person is first infected by a virus
until the appearance of the earliest symptoms) of
two to eight weeks, infected persons develop fever,
may feel nauseous, lose their appetite, and often have
discomfort or actual pain in the right upper part
of the abdomen where the liver is located. Some
develop yellowing of the skin and the whites of the
eyes ( jaundice). Most often the illness is mild and
disappears within a few weeks with no lasting effects.
Children younger than 14 years and persons over age
50 seldom have jaundice or show other clinical signs
of hepatitis.
Hepatitis E never becomes a chronic (long-lasting)
illness, but on rare occasions the acute illness
damages and destroys so many liver cells that the
liver can no longer function. This is called fulminant
liver failure, and may cause death. Pregnant women
are at much higher risk of dying from fulminant liver
failure; this increased risk is not true of any other
type of viral hepatitis. The great majority of patients
who recover from acute infection do not continue
to carry HEV and cannot pass on the infection
to others.

Diagnosis
HEV can be found by microscopically examining
a stool sample, but this is not a reliable test, as the virus
often dies when stored for a short time. Like other
hepatitis viruses, HEV stimulates the body’s immune
system to produce a substance called an antibody,
which can swallow up and destroy the virus. Blood
tests can determine elevated antibody levels, which
indicate the presence of HEV virus in the body.
Unfortunately, such antibody blood tests are not
widely available.

Treatment
There is no way of effectively treating the symptoms of any acute hepatitis, including hepatitis E.
During acute infection, a patient should take a
balanced diet and rest in bed as needed.

KEY TERMS
Antibody—A substance made by the body’s
immune system in response to an invading virus,
the antibodies then attack and destroy the virus.
Incubation period—The time from when a person
is first infected by a virus until the appearance of
the earliest symptoms.
Jaundice—Yellowing of the skin that occurs when
pigments normally eliminated by the liver collect in
high amounts in the blood.
Sanitation—The process of keeping drinking water,
foods, or any anything else with which people
come into contact free of microorganisms such as
viruses.
Vaccine—A substance prepared from a weakened
or killed virus which, when injected, stimulates the
immune system to produce antibodies that can
prevent infection by the natural virus.

die of advanced liver failure. In pregnant women the
death rate is as high as 20%. It is not clear whether
having hepatitis E once guarantees against future
HEV infection.

Prevention
Most attempts to use blood serum containing
HEV antibody to prevent hepatitis in those exposed
to HEV have failed. Hopefully, this approach
can be made to work so that pregnant women
living in endemic areas can be protected. No vaccine is available, though several are being tested.
It also is possible that effective anti-viral drugs
will be found. The best ways to prevent hepatitis E
are to provide safe drinking water and take precautions to use sterilized water and beverages when
traveling.
Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
OTHER

Prognosis
In the United States hepatitis E is not a fatal
illness, but elsewhere about 1–2% of those infected
1782

King, J. W. Bug Bytes. Louisiana State University Medical
Center. <http://www.ccm.lsumc.edu/bugbytes>.

David A. Cramer, MD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Hepatitis G is a newly discovered form of liver
inflammation caused by hepatitis G virus (HGV), a
distant relative of the hepatitis C virus.

Description
HGV, also called hepatitis GB virus, was first
described early in 1996. Little is known about the
frequency of HGV infection, the nature of the illness,
or how to prevent it. What is known is that transfused
blood containing HGV has caused some cases of
hepatitis. For this reason, patients with hemophilia
and other bleeding conditions who require large
amounts of blood or blood products are at risk
of hepatitis G. HGV has been identified in between
1–2% of blood donors in the United States. Also at
risk are patients with kidney disease who have blood
exchange by hemodialysis, and those who inject drugs
into their veins. It is possible that an infected mother
can pass on the virus to her newborn infant. Sexual
transmission also is a possibility.
Often patients with hepatitis G are infected at
the same time by the hepatitis B or C virus, or both.
In about three of every thousand patients with acute
viral hepatitis, HGV is the only virus present. There
is some indication that patients with hepatitis G
may continue to carry the virus in their blood for
many years, and so might be a source of infection in
others.

Causes and symptoms
Some researchers believe that there may be a
group of GB viruses, rather than just one. Others
remain doubtful that HGV actually causes illness.
If it does, the type of acute or chronic (long-lasting)
illness that results is not clear. When diagnosed, acute
HGV infection has usually been mild and brief. There
is no evidence of serious complications, but it is possible that, like other hepatitis viruses, HGV can cause
severe liver damage resulting in liver failure. The virus
has been identified in as many as 20% of patients with
long-lasting viral hepatitis, some of whom also have
hepatitis C.

Antibody—A substance made by the body’s
immune system in response to an invading
virus; antibodies then attack and destroy the
virus.
Hemophilia—A bleeding disorder that often makes
it necessary to give patients dozens or even hundreds of units of blood and blood products over
time.

Efforts are under way, however, to develop a test for
the HGV antibody, which is formed in response to
invasion by the virus. Once antibody is present, however, the virus itself generally has disappeared, making
the test too late to be of use.

Treatment
There is no specific treatment for any form of
acute hepatitis. Patients should rest in bed as needed,
avoid alcohol, and be sure to eat a balanced diet.

Prognosis
What little is known about the course of hepatitis
G suggests that illness is mild and does not last long.
When more patients have been followed up after the
acute phase, it will become clear whether HGV can
cause severe liver damage.

Prevention
Since hepatitis G is a blood-borne infection, prevention relies on avoiding any possible contact with
contaminated blood. Drug users should not share
needles, syringes, or other equipment.
Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave.,
Cedar Grove, NJ 07009. (800) 223-0179.
<http://www.liverfoundation.org>.

David A. Cramer, MD

Diagnosis
The only method of detecting HGV is a complex
and costly DNA test that is not widely available.
GALE ENCYCLOPEDIA OF MEDICINE

Hepatitis virus studies see Hepatitis virus
tests
1783

Hepatitis G

KEY TERMS

Hepatitis G

Hepatitis virus tests

Hepatitis virus tests
Definition
Viral hepatitis is any type of liver inflammation
caused by a viral infection. The three most common
viruses now recognized to cause liver disease are hepatitis A, hepatitis B, and hepatitis non-A, non-B (also
called hepatitis C). Several other types have been
recognized: hepatitis D, hepatitis E, and the recently
identified hepatitis G. A seventh type (hepatitis F) is
suspected but not yet confirmed.

Purpose
The different types of viral hepatitis produce similar symptoms, but they differ in terms of transmission,
course of treatment, prognosis, and carrier status.
When the clinical history of a patient is insufficient
for differentiation, hepatitis virus tests are used as an
aid in diagnosis and in monitoring the course of the
disease. These tests are based primarily on antigenantibody reactions—an antigen being a protein foreign
to the body, and an antibody another type of protein
manufactured by lymphocytes (a type of white blood
cell) to neutralize the antigen.

can be mild or severe, and it can be acute (of limited
duration) or chronic (ongoing). It is usually spread by
sexual contact with another infected person, through
contact with infected blood, by intravenous drug use,
or from mother to child at birth.
HBV, also called the Dane particle, is composed
of an inner protein core surrounded by an outer
protein capsule. The outer capsule contains the hepatitis B surface antigen (HBsAg), formerly called the
Australia antigen. The inner core contains HBV core
antigen (HBcAg), and the hepatitis B e-antigen
(HBeAg). Antibodies to these antigens are called
anti-HBs, anti-HBc, and anti-HBe. Testing for these
antigens and antibodies is as follows:


Hepatitis B surface antigen (HBsAg). This is the first
test for hepatitis B to become abnormal. HBsAg
begins to elevate before the onset of clinical symptoms, peaks during the first week of symptoms, and
usually disappears by the time the accompanying
jaundice (yellowing of the skin and other tissues)
begins to subside. HBsAg indicates an active HBV
infection. A person is considered to be a carrier if this
antigen persists in the blood for six or more months.



Hepatitis B surface antibody (anti-HBs). This
appears approximately one month after the disappearance of the HBsAg, signaling the end of the
acute infection period. Anti-HBs is the antibody
that demonstrates immunity after administration of
the hepatitis B vaccine. Its presence also indicates
immunity to subsequent infection.



Hepatitis B core antigen (HBcAg). No tests are commercially available to detect this antigen.



Hepatitis B core antibody (anti-HBc). This appears
just before acute hepatitis develops and remains elevated (although it slowly declines) for years. It is also
present in chronic hepatitis. The hepatitis B core
antibody is elevated during the time lag between the
disappearance of the hepatitis B surface antigen and
the appearance of the hepatitis B surface antibody in
an interval called the ‘‘window.’’ During this time,
the hepatitis B core antibody is the only detectable
marker of a recent hepatitis B infection.



Hepatitis B e-antigen (HBeAg). This is more useful
as an index of infection than for diagnostic purposes.
The presence of this antigen correlates with early and
active disease, as well as with high infectivity in
patients with acute HBV infection. When HBeAg
levels persist in the blood, the development of
chronic HBV infection is suspected.



Hepatitis B e-antibody (anti-HBe). In the bloodstream, this indicates a reduced risk of infectivity in

Description
There are five major types of viral hepatitis. The
diseases, along with the antigen-antibody tests available to aid in diagnosis, are described below.
Hepatitis A
Commonly called infectious hepatitis, this is
caused by the hepatitis A virus (HAV). It is usually a
mild disease, most often spread by food and water
contamination, but sometimes through sexual contact. Immunologic tests are not commercially available for the HAV antigen, but two types of antibodies
to HAV can be detected. IgM antibody (anti-HAV/
IgM), appears approximately three to four weeks
after exposure and returns to normal within several
months. IgG (anti-HAV/IgG) appears approximately
two weeks after the IgM begins to increase and
remains positive. Acute hepatitis is suspected if IgM
is elevated; conversely, if IgG is elevated without IgM,
a convalescent stage of HAV is presumed. IgG antibody can remain detectable for decades after infection.
Hepatitis B
Commonly known as serum hepatitis, this is
caused by the hepatitis B virus (HBV). The disease
1784

GALE ENCYCLOPEDIA OF MEDICINE

Hepatitis C
Previously known as non-A, non-B hepatitis, this
disease is primarily caused by the hepatitis C virus
(HCV). It is generally mild, but more likely than hepatitis B to lead to chronic liver disease, possible liver
failure, and the eventual need for transplant. Chronic
carrier states develop in more than 80% of patients,
and chronic liver disease is a major problem. As many
as 20% of patients with chronic hepatitis C will
develop liver failure or liver cancer. HCV is spread
through sexual contact, as well as through sharing
drug needles, although nearly half of infections can’t
be traced as to origin.
Hepatitis C is detected by HCV serology (tests
on blood sera). A specific type of assay called
enzyme-linked immunosorbent assay (ELISA) was
developed to detect antibody to hepatitis C for diagnostic purposes, as well as for screening blood donors.
Most cases of post-transfusion non-A, non-B hepatitis
are caused by HCV, but application of this test has
virtually eliminated post-transfusion hepatitis. An
HCV viral titer to detect HCV RNA in the blood is
now available, and recently, IgM anti-HCV core is
proving to be a useful acute marker for HCV infection.

rare in the United States. There are currently no antigen or antibody tests widely available to accurately
detect HEV.

Preparation
Hepatitis virus tests require a blood sample. It is
not necessary for the patient to withhold food or fluids
before any of these tests, unless requested to do so by
the physician.

Risks
Risks for these tests are minimal for the patient,
but may include slight bleeding from the blooddrawing site, fainting or feeling lightheaded after venipuncture, or hematoma (blood accumulating under
the puncture site).

Normal results
Reference ranges for the antigen/antibody tests
are as follows:


hepatitis A antibody, IgM: Negative



hepatitis B core antibody: Negative



hepatitis B e antibody: Negative



hepatitis B e-antigen: Negative



hepatitis B surface antibody: Varies with clinical
circumstance (Note: As the presence of anti-HBs
indicates past infection with resolution of previous
hepatitis B infection, or vaccination against hepatitis
B, additional patient history may be necessary for
diagnosis.)



hepatitis B surface antigen: Negative



hepatitis C serology: Negative



hepatitis D serology: Negative.

Hepatitis D
Also called delta hepatitis, this is caused by the
hepatitis D virus (HDV). The disease occurs only in
those who have HBV in the blood from a past or
simultaneously occurring infection. Experts believe
transmission may occur through sexual contact, but
further research is needed to confirm that. Most cases
occur among those who are frequently exposed to
blood and blood products. Many cases also occur
among drug users who share contaminated needles.
Hepatitis D virus (HDV) antigen can be detected by
radioimmunoassay within a few days after infection,
together with IgM and total antibodies to HDV.
Hepatitis E
Caused by the hepatitis E virus (HEV), this is
actually another type of non-A, non-B hepatitis. The
virus is most often spread through fecally contaminated water, but the role of person-to-person transmission is unclear. This form of hepatitis is quite
GALE ENCYCLOPEDIA OF MEDICINE

Abnormal results
Hepatitis A: A single positive anti-HAV test may
indicate previous exposure to the virus, but due to the
antibody persisting so long in the bloodstream, only
evidence of a rising anti-HAV titer confirms hepatitis
A. Determining recent infection rests on identifying
the antibody as IgM (associated with recent infection).
A negative anti-HAV test rules out hepatitis A.
Hepatitis B: High levels of HBsAg that continue
for three or more months after onset of acute infection
suggest development of chronic hepatitis or carrier
status. Detection of anti-HBs signals late convalescence
1785

Hepatitis virus tests

patients who have previously been HBeAg positive.
Chronic hepatitis B surface antigen carriers can be
positive for either HBeAg or anti-HBe, but are less
infectious when anti-HBe is present. Antibody to
e antigen can persist for years, but usually disappears
earlier than anti-HBs or anti-HBc.

Herbalism, traditional Chinese

or recovery from infection. This antibody remains in
the blood to provide immunity to reinfection.
Hepatitis C (non-A, non-B hepatitis): Anti-HBc
develops after exposure to hepatitis B. As an early
indicator of acute infection, antibody (IgM) to core
antigen (anti-HBc IgM) is rarely detected in chronic
infection, so it is useful in distinguishing acute from
chronic infection, and hepatitis B from non-A, non-B.
Resources

Purpose

BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnosticand
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Hepatobiliary scan see Gallbladder nuclear
medicine scan
Hepatocellular carcinoma see Liver cancer,
primary
Hepatolenticular degeneration see Wilson’s
disease
Hepatoma see Liver cancer, primary
Herbal medicine see Herbalism, western

Herbalism, traditional Chinese
Definition
Chinese herbalism is one of the major components
of traditional Chinese medicine (TCM), or Oriental
medicine (OM). In TCM, herbs are often used in
conjunction with other techniques, such as acupuncture or massage. Chinese herbalism is a holistic
medical system, meaning that it looks at treating a
patient as a whole person, looking at the mental and
spiritual health, as well as the physical health, of the
individual. Illness is seen as a disharmony or imbalance among these aspects of the individual. Chinese
herbalism has been practiced for over 4,000 years.
One of the earliest and certainly the most important Chinese herbal text is the Huang Ti Nei Ching, or
Yellow Emperor’s Classic of Internal Medicine. It is
believed to be authored by Huang Ti during his reign
over China, which started about 2697 B.C. Since that
time, herbal practices have been more extensively documented and refined. In modern China, traditional
Chinese herbalism is taught alongside conventional
1786

Western pharmacology. Chinese herbal remedies
have been used in the West only relatively recently,
over the past two decades. These remedies are more
gentle and natural that conventional medicines. In
addition, they have fewer unpleasant side effects.
Individuals with chronic disorders in particular are
increasingly drawn to the holistic aspect of Chinese
herbalism and TCM in general.

Because it is a safe, inexpensive solution to health
problems of all kinds, Chinese herbalism is very popular in China. In recent years, herbalism has been
modernized with the introduction of quality control.
For example, herbs are subjected to absorption spectrometry to determine levels of heavy metals found in
some. Because they are standardized, Chinese herbs
are safer for self-treatment. This puts the individual,
not the physician, in charge of the individual’s health;
that is a basic goal of Chinese herbalism.
Chinese herbalism offers unique advice regarding
what foods can help and what can hinder, and an
herbalist can help an individual discover what he is
allergic to. In addition, Chinese herbs stimulate the
immune system and provide beneficial nutrients, aside
from their role in curing illness.
At M.D. Anderson Hospital in Texas, medical
research has confirmed that patients undergoing
chemotherapy were shown to have an improved degree
of immune function when they took the tonic herb
astragulus (huang qi). (It is well known that chemotherapy suppresses the immune system.) Research
also showed that T-cell and macrophage activity and
interferon production was increased in patients using
the Chinese herbs ganoderma, lentinus, and polyporous, helping the body fight cancer cells. Agents also
found in ganoderma were found to inhibit platelet
aggregation and thrombocyte formation, which
would be helpful to counter circulation and heart
problems.
An ingredient of ginseng was found to promote
adrenal function, which would give the herb properties of enhancing many hormone functions in the
body.

Description
Origins
HISTORICAL BACKGROUND. Traditional Chinese
medicine originated in the region of eastern Asia that
today includes China, Tibet, Vietnam, Korea, and
Japan. Tribal shamans and holy men who lived as

GALE ENCYCLOPEDIA OF MEDICINE

Herb

Purpose

Astragalus
(huang chi)
Don Quai (dang
qui)

Builds immune systemp offsets side effects of
chemotherapy and radiation treatments
Stimulates the production of red blood cells and bone
marrow; increases cardiovascular endurance; regulates menstrual disorders

Ginseng (ren
shen)
Reishi mushroom
(ling zhi)
Schisandra (wu
wei zu)

Increases physical stamina; general tonic
Eliminates toxins; increases physical stamina
Prevents fluid loss, e.g., excessive sweating, runny
nose, incontinence

hermits in the mountains of China as early as 3500 B.C.
practiced what was called the ‘‘Way of Long Life.’’ This
regimen included a diet based on herbs and other plants;
kung-fu exercises; and special breathing techniques that
were thought to improve vitality and life expectancy.
After the Han dynasty, the next great age of
Chinese medicine was under the Tang emperors, who
ruled from A.D. 608 to 906. The first Tang emperor
established China’s first medical school in A.D. 629
Under the Song (A.D.) 960–1279 and Ming
(A.D. 1368–1644) dynasties, new medical schools were
established, their curricula and qualifying examinations were standardized, and the traditional herbal
prescriptions were written down and collected into
encyclopedias. One important difference between the
development of medicine in China and in the West is
the greater interest in the West in surgical procedures
and techniques.
PHILOSOPHICAL BACKGROUND: THE COSMIC AND
NATURAL ORDER. In Taoist thought, the Tao, or

universal first principle, generated a duality of opposing principles that underlie all the patterns of nature.
These principles, yin and yang, are mutually dependent as well as polar opposites. They are basic concepts in traditional Chinese medicine. Yin represents
everything that is cold, moist, dim, passive, slow,
heavy, and moving downward or inward; while yang
represents heat, dryness, brightness, activity, rapidity,
lightness, and upward or outward motion. Both forces
are equally necessary in nature and in human wellbeing, and neither force can exist without the other.
The dynamic interaction of these two principles is
reflected in the cycles of the seasons, the human life
cycle, and other natural phenomena. One objective
of traditional Chinese medicine is to keep yin and
yang in harmonious balance within a person.
GALE ENCYCLOPEDIA OF MEDICINE

In addition to yin and yang, Taoist teachers also
believed that the Tao produced a third force, primordial energy or qi (also spelled chi or ki). The interplay
between yin, yang, and qi gave rise to the Five
Elements of water, metal, earth, wood, and fire.
These entities are all reflected in the structure and
functioning of the human body.
THE HUMAN BEING. Traditional Chinese physicians did not learn about the structures of the human
body from dissection because they thought that cutting open a body insulted the person’s ancestors.
Instead they built up an understanding of the location
and functions of the major organs over centuries
of observation, and then correlated them with the
principles of yin, yang, qi, and the Five Elements.
Thus wood is related to the liver (yin) and the gall
bladder (yang); fire to the heart (yin) and the small
intestine (yang); earth to the spleen (yin) and the stomach (yang); metal to the lungs (yin) and the large
intestine (yang); and water to the kidneys (yin) and
the bladder (yang). The Chinese also believed that the
body contains Five Essential Substances, which
include blood, spirit, vital essence (a principle of
growth and development produced by the body from
qi and blood), Fluids (all body fluids other than blood,
such as saliva, spinal fluid, sweat, etc.), and qi.

Chinese herbal treatment differs from Western
herbalism in several respects. In Chinese practice, several different herbs may be used, according to each
plant’s effect on the individual’s Qi and the Five
Elements. There are many formulas used within traditional Chinese medicine to treat certain common
imbalance patterns. These formulas can be modified
to fit specific individuals more closely.
A traditional Chinese herbal formula typically
contains four classes of ingredients, arranged in a
hierarchical order: a chief (the principal ingredient,
chosen for the patient’s specific illness); a deputy (to
reinforce the chief’s action or treat a coexisting condition); an assistant (to counteract side effects of the first
two ingredients); and an envoy (to harmonize all the
other ingredients and convey them to the parts of the
body that they are to treat).
Methods of diagnosis
A Chinese herbalist will not prescribe a particular
herb on the strength of symptoms only, but will take
into consideration the physical condition, emotional
health, and mental state of the patient. He or she may
look at the condition of the patient’s hair, skin, and
tongue, as well as the appearance of the eyes, lips, and
general complexion. The practitioner then listens to
1787

Herbalism, traditional Chinese

Five Popular Chinese Herbs Used In The U.S.

Herbalism, traditional Chinese

the sounds the body makes when breathing. He or she
may smell the breath, body odor, or sputum in
diagnosis.
TCM practitioners take an extensive medical history of a patient. He or she may ask about dietary
habits, lifestyle, and sleep patterns. The patient will be
questioned about chief medical complaints, as well as
on his or her particular emotional state and sexual
practices.
Chinese herbalists employ touch as a diagnostic
tool. They may palpate the body or use light massage
to assess the patient’s physical health. Another chief
component of Chinese medical diagnosis is pulse
diagnosis, or sphygmology. This is a very refined
art that takes practitioners years to master. Some
practitioners can detect 12 different pulse points
that correspond to the 12 major organs in Chinese
medicine. There are over 30 pulse qualities that practitioners are able to detect on each point. The strength,
speed, quality, and rhythm of the pulse, to name a
few, will be determined before a diagnosis is given.
Herbs
Chinese herbs may be used alone or in combination. Relatively few are used alone for medicinal purposes. Practitioners believe that illness can be
effectively treated by combining herbs based on their
various characteristics and the patient’s overall health.
Every herb has four basic healing properties: nature,
taste, affinity, and effect.
An herb’s nature is described according to its yin
or yang characteristics. Yang, or warming, herbs treat
cold deficiencies. They are frequently used in the treatment of the upper respiratory tract, skin, or extremities. Yin, or cooling, herbs, treat hot excess conditions.
They are most often used to treat internal conditions
and problems with organs. Herbs can also be neutral
in nature.
An herb’s taste does not refer to its flavor, but to
its effect on qi, blood, fluids, and phlegm. Sour herbs
have a concentrating action. They are prescribed to
treat bodily excess conditions, such as diarrhea, and
concentrate qi. Bitter herbs have an eliminating or
moving downward action. They are used to treat
coughs, constipation, and heart problems. Sweet or
bland herbs have a harmonizing action. They are
used as restorative herbs and to treat pain. Spicy
herbs have a stimulating action. They are prescribed
to improve blood and qi circulation. Salty herbs have a
softening action. They are used to treat constipation
and other digestion problems.
1788

An herb’s affinity describes its action on a specific
bodily Organ. (Note that Chinese medicine does not
have the anatomical correlation for organ names.
They correspond more closely to the organ’s function.) Sour herbs have an affinity for the Liver and
Gallbladder. Bitter herbs act on the Heart and Small
Intestine. Sweet and bland herbs affect the Stomach
and Spleen. Spicy herbs have an affinity for Lungs and
Large Intestine, whereas salty herbs act on the
Kidneys and Bladder.
Chinese herbs are lastly classified according to
their specific actions, which are divided into four
effects. Herbs that dispel are used to treat an accumulation, sluggishness, or spasm by relaxing or redistributing. Herbs with an astringent action are used to
consolidate or restrain a condition characterized by
discharge or excessive elimination. Herbs that purge
treat an obstruction or ‘‘poison’’ by encouraging elimination and detoxification. Tonifying herbs nourish,
support, and calm where there is a deficiency.
Treatment of diabetes
The incidence of diabetes has increased quite dramatically in recent years, especially in the United
States, where in general people take less exercise, and
food is taken in greater quantity with a general reduction in quality. This has lead to a scramble to find new
solutions to the problem, and many researchers have
focused their interest on Chinese herbal remedies. In
the search for more effective and more convenient
treatments, the alkaloid berberine has come under
close scrutiny for its many uses, among them the treatment of diabetes. In trials, rats given a mixture of
berberine and alloxan showed less likelihood of incurring a rise in blood sugar. Patients suffering from type
II diabetes who were given between 300 and 600 mg of
berberine daily for between one and three months,
showed a reduction in blood sugar levels, when taken
in conjunction with a controlled diet.
Treatment of AIDS and cancer
Independent researchers are investigating indications that Chinese herbalism can reduce the toxicity of
chemotherapy and other medications, in addition to
stimulating immune responses.

Preparations
Those who are unfamiliar with Chinese herbs and
their uses should consult a practitioner before starting
any treatment. Once a remedy is prescribed, it may be
found at Oriental markets or health food stores. The
GALE ENCYCLOPEDIA OF MEDICINE

Absorption spectrometry—A scientific procedure
to determine chemical makeup of samples.
Interferon—A substance proved to be necessary in
the body to help fight cancer cells.
Immune function—The body’s defense system
against bacteria, viruses and fungi, and any malfunction of the organism.
Pharmaco-dynamics—The study of the relationships and interactions of herbs.
Platelet aggregation—The clumping together of
blood cells, possibly forming a clot.
Thrombocyte—Another name for platelet.

remedies used in Chinese herbalism are standardized
and sold prepared for use, with instructions for
dosage. A Chinese herbalist may prescribe herbs to
be made into tea, or taken as capsules.

United States agencies, including the National
Institutes of Health, the Office of Alternative
Medicine, and the Food and Drug Administration
are currently investigating Chinese herbal medicine
as well as acupuncture and Tui na massage. In general,
however, Western studies of Chinese medicine focus
on the effects of traditional treatments and the reasons
for those effects, thus attempting to fit traditional
Chinese medicine within the Western framework
of precise physical measurements and scientific
hypotheses.
Resources
ORGANIZATIONS

The California Association of Acupuncture and Oriental
Medicine. <http://www.CAAOM.ORG/medicine/
overview.htm>.
For help with herbs and a list of practitioners. <http://
www.craneherb.com>.
Institute of Chinese Materia Medica. China Academy of
Traditional Chinese Medicine. Beijing, 100700.
National Center for Complementary and Alternative
Medicine. <http://nccam.nih.gov/nccam>.

Patricia Skinner

Precautions
When treating a patient, the herbalist will aim to
gently ‘‘nudge’’ the system into shape, rather than
producing any immediate reaction. A return to health,
therefore, may take time, and it is important that the
patient realizes the principle of the treatment. Some
practitioners estimate that treatment will take a month
for every year that a chronic condition has existed. The
advantage of the slow pace is that if there is a bad
reaction to any herb, which is rare, it will be mild
because the treatment itself is gentle.
As with most naturopathic therapies, Chinese
herbal remedies work best when taken in conjunction
with a healthy lifestyle and program of exercise.

Side effects
Some Chinese herbs are incompatible with certain
prescription drugs, certain foods, or should not be
taken during pregnancy. To be certain, a Chinese herbalist should be consulted.

Research and general acceptance
At present, there is renewed interest in the West in
traditional Chinese medicine and Chinese herbalism.
Of the 700 herbal remedies used by traditional Chinese
practitioners, over 100 have been tested and found
effective by the standards of Western science. Several
GALE ENCYCLOPEDIA OF MEDICINE

Herbalism, Western
Definition
Western herbalism is a form of the healing arts
that draws from herbal traditions of Europe and the
Americas, and that emphasizes the study and use of
European and Native American herbs in the treatment
and prevention of illness. Western herbalism is based
on physicians’ and herbalists’ clinical experience and
traditional knowledge of medicinal plant remedies
preserved by oral tradition and in written records
over thousands of years. Western herbalism, like the
much older system of traditional Chinese medicine,
relies on the synergistic and curative properties of the
plant to treat symptoms and disease and maintain
health.
Western herbalism is based upon pharmocognosy, the study of natural products. Pharmocognosy
includes the identification, extraction methods, and
applications of specific plant constituents responsible
for specific therapeutic actions, such as the use of
digoxin from Digitalis leaf for heart failure. These
constituents are extracted, purified and studied in
vitro, in vivo, and in clinical research. They may be
1789

Herbalism, Western

KEY TERMS

Herbalism, Western

concentrated to deliver standardized, set doses.
Sometimes, the natural constituent can be synthesized
in the lab, or changed and patented. Practitioners may
choose to use fresh medicinal plants, simple extracts,
or standardized extracts.
In standardized extracts, a specific quantity of a
constituent is called a marker compound, and it may
or may not be the active constituent(s) in the plant
medicine. There are preparations with standardized
active constituent quantities, and preparations with
greater emphasis on quality of crude plant material
and traditional preparation methodology than on
finalized total quantity of marker compounds. The
preference between the two for precision dosing is
philosophical, practical and variable. When using
plant extracts in which the active constituents and
their cofactors are well established, or the therapeutic
and lethal dose are close, standardized products are
often preferred. When using plant extracts whose
active constituents remain obscure, or the active constituents when purified produce weaker therapeutic
results or more undesirable side effects, the products
produced under good manufacturing processes and
according to the traditional National Formulary U. S.
Dispensatory or U. S. Pharmacopeia are preferred.

Purpose
The benefits of botanical medicine may be subtle
or dramatic, depending on the remedy used and
the symptom or problem being addressed. Herbal
remedies usually have a much slower effect than pharmaceutical drugs. Some herbal remedies have a cumulative effect and work slowly over time to restore
balance, and others are indicated for short-term treatment of acute symptoms. When compared to the
pharmaceutical drugs, herbal remedies prepared
from the whole plant have relatively few side effects.
This is due to the complex chemistry and synergistic
action of the full range of phytochemicals present in
the whole plant, and the relatively lower concentrations. They are generally safe when used in properly
designated therapeutic dosages, and less costly than
the isolated chemicals or synthetic prescription drugs
available from western pharmaceutical corporations.

Description
Origins
Over 2,500 years ago Hippocrates wrote, ‘‘In medicine one must pay attention not to plausible theorizing but to experience and reason together.’’
This Greek physician and herbalist from the fourth
1790

century B.C. is considered the father of western medicine. He stressed the importance of diet, water quality,
climate, and social environment in the development of
disease. Hippocrates believed in treating the whole
person, rather than merely isolating and treating
symptoms. He recognized the innate capacity of the
body to heal itself, and emphasized the importance of
keen observation in the medical practice. He recommended simple herbal remedies to assist the body in
restoring health.
Ancient Greek medicine around the fifth century
B.C. was a fertile ground for contrasting philosophies

and religions. Greek physicians were influenced by the
accumulated medical knowledge from Egypt, Persia,
and Babylon. Medical advances flourished and practitioners and scholars were free to study and practice
without religious and secular constraints. In the fourth
century B.C., Theophrastus wrote the Historia
Plantarum, considered to be the founding text in the
science of botany.
During the first century A.D. Dioscorides, a Greek
physician who traveled with the Roman legions, produced five medical texts. His herbal text, known as the
De Materia Medica is considered to be among the
most influential of all western herbal texts. It became
a standard reference for practitioners for the next
1,500 years. This influential book also included information on medicinal herbs and treatments that had
been used for centuries in Indian Ayurvedic medicine.
Galen of Pergamon, who also lived in the first century
A.D., was a Roman physician and student of anatomy
and physiology. He authored a recipe book containing
130 antidotes and medicinal preparations. These elaborate mixtures, known as galenicals, sometimes
included up to one hundred herbs and other substances. This complex approach to herbal medicine
was a dramatic change from the simple remedies
recommended by Hippocrates and employed by traditional folk healers. Galen developed a rigid system of
medicine in which the physician, with his specialized
knowledge of complex medical formulas, was considered the ultimate authority in matters of health care.
The Galenic system, relying on theory and scholarship
rather than observation, persisted throughout the
Middle Ages. The galenical compounds, along with
bloodletting, and purging, were among the drastic
techniques practiced by the medical professionals during those times; however, traditional herbal healers
persisted outside the mainstream medical system.
During the eighth century a medical school was
established in Salerno, Italy, where the herbal
knowledge accumulated by Arab physicians was preserved. The Arabian Muslims conducted extensive
GALE ENCYCLOPEDIA OF MEDICINE

The Middle Ages in Europe were a time of widespread death by plagues and pestilence. The Black
Plague of 1348, particularly, and other health catastrophes in later years, claimed so many lives that
survivors began to lose faith in the dominant Galenic
medical system. Fortunately, the knowledge of traditional herbal medicine had not been lost. Medieval
monks who cultivated extensive medicinal gardens
on the monastery grounds, also patiently copied the
ancient herbal and medical texts. Folk medicine as
practiced in Europe by traditional healers persisted,
even though many women herbalists were persecuted
as witches and enemies of the Catholic church and
their herbal arts were suppressed.
The growing spice trade and explorations to the
New World introduced exotic plants, and a whole new
realm of botanical medicines became available to
Europeans. Following the invention of the printing
press in the fifteenth century, a large number of herbal
texts, also simply called herbals, became available
for popular use. Among them were the beautifully
illustrated works of the German botanists Otto
Brunfels and Leonhard Fuchs published in 1530, and
the Dutch herbal of Belgian physician Rembert
Dodoens, a popular work that was later reproduced
in English. In 1597, the physician and gardener John
Gerard published one of the most famous of the
English herbals, still in print today. Gerard’s herbal,
known as The Herball or General Historie of Plantes
was not an original work. Much of the content
was taken from the translated text of his Belgian
predecessor Dodoens. Gerard did, however, include
descriptions of some of the more than one thousand
species of rare and exotic plants and English flora
from his own garden.
The correspondence of astrology with herbs was
taught by Arab physicians who regarded astrology as
a science helpful in the selection of medicines and in
the treatment of diseases. This approach to western
herbalism was particularly evident in the herbal texts
published in the sixteenth and seventeenth centuries.
One of the most popular and controversial English
herbals is The English Physician Enlarged published
in 1653. The author, Nicholas Culpeper, was an
apothecary by trade. He also published a translation
of the Latin language London Pharmacopoeia into
GALE ENCYCLOPEDIA OF MEDICINE

English. Culpeper was a nonconformist in loyalist
England, and was determined to make medical knowledge more accessible to the apothecaries, the tradesmen who prescribed most of the herbal remedies.
Culpeper’s herbal was criticized by the medical establishment for its mix of magic and astrology with
botanical medicine, but it became one of the most
popular compendiums of botanical medicine of its
day. Culpeper also accepted the so-called ‘‘Doctrine
of Signatures,’’ practiced by medieval monks in their
medicinal gardens. This theory teaches that the
appearance of plants is the clue to their curative
powers. Plants were chosen for treatment of particular
medical conditions based on their associations with
the four natural elements and with a planet or sign.
The place where the plant grows, its dominant physical feature, and the smell and taste of an herb determined the plant’s signature. Culpeper’s herbal is still
in print in facsimile copies, and some pharmocognosists and herbalists in the twenty-first century voice
the same criticisms that Culpeper’s early critics did.
European colonists brought their herbal knowledge and plant specimens to settlements in North
America where they learned from the indigenous
Americans how to make use of numerous nutritive
and medicinal plants, native to the New World.
Many European medicinal plants escaped cultivation
from the early settlements and have become naturalized throughout North America. The first record of
Native American herbalism is found in the manuscript
of the native Mexican Indian physician, Juan
Badianus published in 1552. The American Folk tradition of herbalism developed as a blend of traditional
European medicine and Native American herbalism.
The pioneer necessity for self-reliance contributed
to the perseverance of folk medicine well into the
twentieth century.
In Europe in the seventeenth century, the alchemist
Paracelsus changed the direction of western medicine
with the introduction of chemical and mineral medicines. He was the son of a Swiss chemist and physician.
Paracelsus began to apply chemicals, such as arsenic,
mercury, sulfur, iron, and copper sulfate to treat
disease. His chemical approach to the treatment of
disease was a forerunner to the reliance in the twentieth
century on chemical medicine as the orthodox treatment prescribed in mainstream medical practice.
The nineteenth and twentieth centuries brought a
renewed interest in the practice of western herbalism
and the development of natural therapies and health
care systems that ran counter to the mainstream
methods of combating disease symptoms with synthetic pharmaceuticals.
1791

Herbalism, Western

research on medicinal herbs found in Europe, Persia,
India, and the Far East. Arab businessmen opened the
first herbal pharmacies early in the ninth century. The
Leech Book of Bald, the work of a Christian monk, was
compiled in the tenth century. It preserved important
medical writings that had survived from the work of
physicians in ancient Greece and Rome.

Herbalism, Western

An estimated 2,400 acres of native plant habitat are
lost to development every day. As much as 29% of all
plant life in North America is in danger of extinction,
including some of the most important native medicinal
plants, according to the 1997 World Conservation
Union Red List of Threatened Plants.

A selection of Western herbal medical equipment and traditional herbs, including foxglove (upper right), ginger (center
right), and periwinkle (lower left). (Photo Researchers, Inc.
Reproduced by permission.)

In the late eighteenth century, the German
physician Samuel Hahnemann developed a system of
medicine known as homeopathy. This approach to
healing embraces the philosophy of ‘‘like cures like.’’
Homeopathy uses extremely diluted solutions of
herbs, animal products, and chemicals that are believed
to hold a ‘‘trace memory’’ or energetic imprint of the
substance used. Homeopathic remedies are used to
amplify the patient’s symptoms with remedies that
would act to produce the same symptom in a healthy
person. Homeopathy holds that the symptoms of illness
are evidence of the body’s natural process of healing
and eliminating the cause of the disease.
In 1895, the European medical system known as
Naturopathy was introduced to the North America.
Like homeopathy, this medical approach is based on
the Hippocratic idea of eliminating disease by assisting
the body’s natural healing abilities. The naturopath
uses nontoxic methods to assist the body’s natural
healing processes, including nutritional supplements,
herbal remedies, proper diet, and exercise to restore
health.
Western herbalism is regaining popularity at a
time when the world is assaulted by the stress of
overpopulation and development that threatens the
natural biodiversity necessary for these valuable medicinal plants to survive. The American herb market is
growing rapidly and increasing numbers of individuals
are choosing alternative therapies over the mainstream allopathic western medicine. It is projected
that by the year 2002 consumers will spend more
than seven billion dollars a year on herbal products.
1792

Though research into the efficacy and safety of
traditional herbal remedies is increasing, it has been
limited by the high costs of clinical studies and
laboratory research, and by the fact that whole plants
and their constituents are not generally patentable
(therefore, there is no drug profit after market introduction). Outside the United States, herbalism has
successfully combined with conventional medicine,
and in some countries is fully integrated into the
nations’ health care systems. At the beginning of the
twenty-first century, 80% of the world’s population
continues to rely on herbal treatments. The World
Health Organization, an agency of the United
Nations, promotes traditional herbal medicine for
treatment of many local health problems, particularly in the third world where it is affordable and
already well-integrated into the cultural fabric.
In the United States, the re-emergence in interest
in holistic approaches to health care is evident.
Citizens are demanding access to effective, safe, lowcost, natural medicine. Legislative and societal change
is needed, however, before natural therapies can be
fully integrated into the orthodox allopathic health
care system and provide citizens with a wide range of
choices for treatment. If the current trend continues,
U. S. citizens will benefit from a choice among a
variety of safe and effective medical treatments.
Herbs are generally defined as any plant or plant
part that may be used for medicinal, nutritional, culinary, or other beneficial purposes. The active constituents of plants (if known) may be found in varying
amounts in the root, stem, leaf, flower, and fruit, etc.
of the plant. Herbs may be classified into many
different categories. Some western herbalists categorize
herbal remedies according to their strength, action, and
characteristics. Categories may include sedatives, stimulants, laxatives, febrifuges (to reduce fever), and
many others. One system of classification is based
on a principle in traditional Chinese medicine that
categorizes herbs into four classes: tonics, specifics,
heroics, or cleansers and protectors. Within these
broad classifications are the numerous medicinal
actions of the whole herb which may be due to a specific
chemical or combination of chemicals in the plant.


Tonics. Herbs in this classification are also known
as alteratives in western herbalism. They are
GALE ENCYCLOPEDIA OF MEDICINE



Specifics. Herbs in this classification are strong and
specific in their therapeutic action. They are generally used for short periods of time in smaller dosages
to treat acute conditions. Herbs classified as specifics
are not used beyond the therapeutic treatment
period. Echinacea is a specific herb.



Heroic. These herbs offer high potency but are
potentially toxic, and should not be used in selftreatment. Because the therapeutic dosage may be
close to the lethal dosage, these herbs are presented
cautiously and closely monitored or avoided
by trained clinicians. They should not be used continuously or without expert supervision. Poke
(Phytolacca americana) is an example of a heroic
remedy.



Cleansers and protectors. These herbs, plants, and
plant tissues remove wastes and pollutants, while
minimally affecting regular body processes. An example of a cleanser is pectin. Pectins are the water soluble
substances that bind cell walls in plant tissues, and
some believe that they help remove heavy metals and
environmental toxins from the body.

Preparations
Herbal preparations are commercially available
in a variety of forms including tablets or capsules,
tinctures, teas, fluid extracts, douches, washes,
suppositories, dried herbs, and many other forms.
The medicinal properties of herbs are extracted
from the fresh or dried plant parts by the use of
solvents appropriate to the particular herb. Alcohol,
oil, water, vinegar, glycerin, and propylene glycol
are some of the solvents used to extract and concentrate the medicinal properties. Steam distillation
and cold-pressing techniques are used to extract the
essential oils. The quality of any herbal remedy and
the potency of the phytochemicals found in the herb
depends greatly on the conditions of weather and
soil where the herb was grown, the timing and care
in harvesting, and the manner of preparation and
storage.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
In vitro—A biological reaction occurring in a
laboratory apparatus.
In vivo—Occurring in a living organism.
Phyto-, as in phytochemical, phytomedicinal, and
phytotherapy—Meaning, or pertaining to, a plant
or plants.
Wildcrafting—Gathering of herbs or other natural
materials.

Precautions
Herbal remedies prepared by infusion, decoction,
or alcohol tincture from the appropriate plant part,
such as the leaf, root, or flower are generally safe
when ingested in properly designated therapeutic
dosages. However, many herbs have specific contraindications for use when certain medical conditions
are present. Not all herbal remedies may be safely
administered to infants or small children. Many herbs
are not safe for use by pregnant or lactating women.
Some herbs are toxic, even deadly, in large amounts,
and there is little research on the chronic toxicity that
may result from prolonged use. Herbal remedies are
sold in the United States as dietary supplements and
are not regulated for content or efficacy. Self-diagnosis
and treatment with botanical medicinals may be risky.
A consultation with a clinical herbalist, Naturopathic
physician, or certified clinical herbalist is prudent
before undertaking a course of treatment.
Essential oils are highly concentrated and should
not be ingested as a general rule. They should also be
diluted in water or in a non-toxic carrier oil before
application to the skin to prevent contact dermatitis or
photo-sensitization. The toxicity of the concentrated
essential oil varies depending on the chemical constituents of the herb.
The American Professor of Pharmacognosy, Varro
E. Tyler, believes that ‘‘herbal chaos’’ prevails in the
United States with regard to herbs and phytomedicinals. In part he blames the herb producers and marketers of crude herbs and remedies for what he terms
unproven hyperbolic, poor quality control, deceptive
labeling, resistance to standardization of dosage forms,
and continued sale of herbs determined to be harmful.

Side effects
Herbs have a variety of complex phytochemicals
that act on the body as a whole or on specific organs
1793

Herbalism, Western

generally mild in their action and act slowly in the
body, providing gentle stimulation and nutrition to
specific organs and systems. Tonic herbs act over
time to strengthen and nourish the whole body.
These herbs are generally safe and may be used
regularly, even in large quantities. These tonic
herbs are known as ‘‘superior’’ remedies in traditional Chinese medicine. The therapeutic dose of
tonic remedies is far removed from the possible
toxic dose. American ginseng is an example of a
tonic herb.

Hereditary fructose intolerance

and systems. Some of these chemical constituents
are mild and safe, even in large doses. Other herbs contain chemicals that act more strongly and may be toxic
in large doses or when taken continuously. Drug interactions are possible with certain herbs when combined
with certain pharmaceutical drugs. Some herbs are tonic
in a small amount and toxic in larger dosages.

medicine therapies ‘‘to the same standard of scientific
rigor as more traditional health care interventions.’’
That Commission is charged with recommending federal
guidelines and legislation regarding the use of alternative
medical therapies in the twenty-first century.
Resources
PERIODICALS

Research and general acceptance
Western herbalism is experiencing a revival of
popular and professional interest. The number of
training schools and qualified herbal practitioners is
growing to meet the demand. Western herbalism is
incorporated into the medical practice of licensed
Naturopathic doctors, who receive special training
in clinical herbalism. Folk herbalists, heir to the
continuing oral traditions passed from generation to
generation in many rural areas, as well as amateur,
self-taught herbalists, keep the practice of botanical
medicine alive at the grassroots level. Traditional
western herbalism relies on traditional use and materia
medica, folk wisdom, and recent clinical research and
advances in the extraction processes. These advances
provide increased quality control on the concentration
and potency of the active ingredients. Western physicians, educated in allopathic medicine, typically
receive no training in the use of herbs. These doctors
rely on pharmaceutical drugs for their patients, and
some cite the following reasons for continuing to do
so: lack of standardized dosages, lack of quality
control in the preparation of herbal medicinals, and
the dearth of clinical research verifying the safety and
effectiveness of many traditional herbal remedies.
Herbalism is widely practiced throughout Europe,
particularly in England, France, Italy, and Germany
where phytomedicinals are available in prescription
form and as over-the-counter remedies. In Germany,
plant medicines are regulated by a special government
body known as the Commission E. In the United States,
however, despite increasing popularity, traditional herbalism is not integrated into the allopathic medical
system. Phytomedicinals are sold as dietary supplements
rather than being adequately researched and recognized
as safe and effective drugs. The Dietary Supplement
Health and Education Act of 1994 circumvented a U. S.
Food and Drug Administration (FDA) effort to effectively remove botanicals from the marketplace and
implement regulations restricting sale. Massive popular
outcry against the proposed regulations on the sale of
herbs and phytomedicinals resulted in this Congressional
action. In 2000, U.S. President Bill Clinton, by executive
order, created the White House Commission on
Alternative Medicine in an effort to hold alternative
1794

Deneen, Sally, with Rembert, Tracey. ‘‘Uprooted, The
Worldwide Plant Crisis Is Accelerating.’’ E Magazine
July-August 1999: 36-40.
Liebmann, Richard, N.D. ‘‘United Plant Savers—Planting
the Future.’’ PanGaia 22 (Winter 1999-2000): 23- 26.
ORGANIZATIONS

National Center for the Preservation of Medicinal Herbs.
3350 Beech Grove Road, Rutland, Ohio 45775.
(740)742- 4401.
United Plant Savers. P.O. Box 98, East Barre, Vermont
05649. (802) 479-9825. <http://www.plantsavers.org>.
OTHER

Hobbs, Christopher. ‘‘Specific and Tonic Immune Herbs:
Exploring a Practical System of Western Herbalism.’’
Health World. <http://www.healthy.net>.
Oracle Tree New Age Mall. ‘‘Western Medical Astrology:
A Brief History.’’ <http://ww.oracletree.com/
avalonphysics/wesmedas.html>.
Wicke, Roger, Ph.D. ‘‘A World History of Herbology
and Herbalism: Oppressed Arts.’’ Rocky Mountain
Herbal Institute. <http://www.rmhiherbalorg/a/
f.ahrl.hist.html>.

Clare Hanrahan

Herbs see Echinacea; Ginkgo biloba;
Ginseng; Saw palmetto; St. John’s wort
Hereditary cerebral hemorrhage with
amyloidosis see Cerebral amyloid
angiopathy
Hereditary chorea see Huntington’s
disease

Hereditary fructose
intolerance
Definition
Hereditary fructose intolerance is an inherited
condition where the body does not produce the chemical needed to break down fructose (fruit sugar).
GALE ENCYCLOPEDIA OF MEDICINE

Fructose is a sugar found naturally in fruits, vegetables, honey, and table sugar. Fructose intolerance is
a disorder caused by the body’s inability to produce
an enzyme called aldolase B (also called fructose
1-phosphate aldolase) that is necessary for absorption
of fructose. The undigested fructose collects in the
liver and kidneys, eventually causing liver and kidney
failure. One person in about 20,000 is born with this
disorder. It is reported more frequently in the United
States and Northern European countries than in other
parts of the world. It occurs with equal frequency in
males and females.

Causes and symptoms
Fructose intolerance is an inherited disorder
passed on to children through their parents’ genes.
Both the mother and father have the gene that causes
the condition, but may not have symptoms of fructose
intolerance themselves. (This is called an autosomal
recessive pattern of inheritance.) The disorder will not
be apparent until the infant is fed formula, juice, fruits,
or baby foods that contain fructose. Initial symptoms
include vomiting, dehydration, and unexplained fever.
Other symptoms include extreme thirst and excessive
urination and sweating. There will also be a loss of
appetite and a failure to grow. Tremors and seizures
caused by low blood sugar can occur. The liver
becomes swollen and the patient becomes jaundiced
with yellowing of the eyes and skin. Left untreated,
this condition can lead to coma and death.

Diagnosis
Urine tests can be used to detect fructose sugar in
the urine. Blood tests can also be used to detect hyperbilirubinemia and high levels of liver enzymes in the
blood. A liver biopsy may be performed to test for
levels of enzymes present and to evaluate the extent
of damage to the liver. A fructose-loading test where
a dose of fructose is given to the patient in a wellcontrolled hospital or clinical setting may also be
used to confirm fructose intolerance. Both the biopsy
and the loading test can be very risky, particularly in
infants that are already sick.

Treatment
Once diagnosed, fructose intolerance can be
successfully treated by eliminating fructose from the
diet. Patients usually respond within three to four
weeks and can make a complete recovery if fructosecontaining foods are avoided. Early recognition and
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Aldolase B—Also called fructose 1-phosphate
aldolase, this chemical is produced in the liver,
kidneys, and brain. It is needed for the breakdown
of fructose, a sugar found in fruits, vegetables,
honey, and other sweeteners.
Hyperbilirubinemia—A condition where there is
a high level of bilirubin in the blood. Bilirubin is a
natural by-product of the breakdown of red blood
cells, however, a high level of bilirubin may indicate a problem with the liver.
Liver biopsy—A surgical procedure where a small
piece of the liver is cut out for examination. A needle
or narrow tube may be inserted either directly
through the skin and muscle or through a small
incision and passed into the liver for collection of
a sample of liver tissue.

treatment of the disease is important to avoid damage
to the liver, kidneys, and small intestine.

Prognosis
If the condition is not recognized and the diet is
not well controlled, death can occur in infants or
young children. With a well-controlled diet, the child
can develop normally.

Prevention
Carriers of the gene for hereditary fructose intolerance can be identified through DNA analysis.
Anyone who is known to carry the disease or who
has the disease in his or her family can benefit from
genetic counseling. Since this is a hereditary disorder,
there is currently no known way to prevent it other
than assisting at-risk individuals with family planning
and reproductive decisions.
Resources
ORGANIZATIONS

National Institutes of Health. National Institute of
Diabetes, Digestive and Kidney Diseases. Building 31,
Room 9A04, 31 Center Drive, Bethesda, MD 208922560. (301) 496-3583.
OTHER

‘‘What Is Hereditary Fructose Intolerance?’’ Hereditary
Fructose Intolerance & Aldolase Homepage.
<http://www.bu.edu/aldolase>.

Altha Roberts Edgren
1795

Hereditary fructose intolerance

Description

Hernia

Hereditary hemorrhagic
telangiectasia
Definition
Hereditary hemorrhagic telangiectasia is an inherited condition characterized by abnormal blood vessels which are delicate and prone to bleeding.
Hereditary hemorrhagic telangiectasia is also known
as Rendu-Osler-Weber disease.

Description

KEY TERMS
Autosomal dominant—A pattern of inheritance in
which the dominant gene on any non-sex chromosome carries the defect.
Chromosome—A threadlike structure in the cell
which transmits genetic information.

Prognosis

The term telangiectasia refers to a spot formed,
usually on the skin, by a dilated capillary or terminal
artery. In hereditary hemorrhagic telangiectasia these
spots occur because the blood vessel is fragile and bleeds
easily. The bleeding may appear as small, red or reddish-violet spots on the face, lips, inside the mouth and
nose or the tips of the fingers and toes. Other small
telangiectasias may occur in the digestive tract.

In most people, recurrent bleeding results in an
iron deficiency. It is usually necessary to take iron
supplements.

Unlike hemophilia, where bleeding is caused by an
ineffective clotting mechanism in the blood, bleeding
in hereditary hemorrhagic telangiectasia is caused by
fragile blood vessels. However, like hemophilia, bleeding may be extensive and can occur without warning.

Resources

Prevention
Hereditary hemorrhagic telangiectasia is an inherited disorder and cannot be prevented.

ORGANIZATIONS

American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://www.ama-assn.org>.
Association of Birth Defect Children. 3526 Emerywood
Lane, Orlando, FL, 32806. (305) 859-2821.

Causes and symptoms
Hereditary hemorrhagic telangiectasia, an autosomal dominant inherited disorder, occurs in one in
50,000 people.
Recurrent nosebleeds are a nearly universal symptom in this condition. Usually the nosebleeds begin in
childhood and become worse with age. The skin
changes begin at puberty, and the condition becomes
progressively worse until about 40 years of age, when
it stabilizes.

Dorothy Elinor Stonely

Hereditary hyperuricemia see Lesch-Nyhan
syndrome
Hereditary spinocerebellar ataxia see
Friedreich’s ataxia
Hermaphroditism see Intersex states

Diagnosis
The physician will look for red spots on all areas of
the skin, but especially on the upper half of the body,
and in the mouth and nose and under the tongue.

Treatment
There is no specific treatment for hereditary
hemorrhagic telangiectasia. The bleeding resulting
from the condition can be stopped by applying compresses or direct pressure to the area. If necessary, a
laser can be used to destroy the vessel. In severe cases,
the leaking artery can be plugged or covered with a
graft from normal tissue.
1796

Hernia
Definition
Hernia is a general term used to describe a bulge
or protrusion of an organ through the structure or
muscle that usually contains it.

Description
There are many different types of hernias. The
most familiar type are those that occur in the abdomen, in which part of the intestines protrude through
the abdominal wall. This may occur in different areas
GALE ENCYCLOPEDIA OF MEDICINE

An inguinal hernia appears as a bulge in the groin
and may come and go depending on the position of the
person or their level of physical activity. It can occur
with or without pain. In men, the protrusion may
descend into the scrotum. Inguinal hernias account
for 80% of all hernias and are more common in men.
Femoral hernias are similar to inguinal hernias
but appear as a bulge slightly lower. They are more
common in women due to the strain of pregnancy.
A ventral hernia is also called an incisional hernia
because it generally occurs as a bulge in the abdomen
at the site of an old surgical scar. It is caused by
thinning or stretching of the scar tissue, and occurs
more frequently in people who are obese or pregnant.
An umbilical hernia appears as a soft bulge at the
navel (umbilicus). It is caused by a weakening of the
area or an imperfect closure of the area in infants. This
type of hernia is more common in women due to
pregnancy, and in Chinese and black infants. Some
umbilical hernias in infants disappear without treatment within the first year.
A hiatal or diaphragmatic hernia is different from
abdominal hernias in that it is not visible on the outside of the body. With a hiatal hernia, the stomach
bulges upward through the muscle that separates the
chest from the abdomen (the diaphragm). This type of
hernia occurs more often in women than in men, and it
is treated differently from other types of hernias.

Causes and symptoms
Most hernias result from a weakness in the
abdominal wall that either develops or that an infant
is born with (congenital). Any increase in pressure in
the abdomen, such as coughing, straining, heavy
lifting, or pregnancy, can be a considered causative
factor in developing an abdominal hernia. Obesity or
recent excessive weight loss, as well as aging and
previous surgery, are also risk factors.
Most abdominal hernias appear suddenly when
the abdominal muscles are strained. The person may
feel tenderness, a slight burning sensation, or a feeling
of heaviness in the bulge. It may be possible for the
person to push the hernia back into place with gentle
pressure, or the hernia may disappear by itself when
the person reclines. Being able to push the hernia back
is called reducing it. On the other hand, some hernias
cannot be pushed back into place, and are termed
incarcerated or irreducible.
GALE ENCYCLOPEDIA OF MEDICINE

A hiatal hernia may also be caused by obesity,
pregnancy, aging, or previous surgery. About 50% of
all people with hiatal hernias do not have any symptoms.
If symptoms exist they will include heartburn, usually
30–60 minutes following a meal. There may be some mid
chest pain due to gastric acid from the stomach being
pushed up into the esophagus. The pain and heartburn
are usually worse when lying down. Frequent belching
and feelings of abdominal fullness may also be present.

Diagnosis
Generally, abdominal hernias need to be seen and
felt to be diagnosed. Usually the hernia will increase in
size with an increase in abdominal pressure, so the
doctor may ask the person to cough while he or she
feels the area. Once a diagnosis of an abdominal
hernia is made, the doctor will usually send the person
to a surgeon for a consultation. Surgery provides the
only cure for a hernia through the abdominal wall.
With a hiatal hernia, the diagnosis is based on the
symptoms reported by the person. The doctor may
then order tests to confirm the diagnosis. If a barium
swallow is ordered, the person drinks a chalky white
barium solution, which will help any protrusion
through the diaphragm show up on the x ray that
follows. Currently, a diagnosis of hiatal hernia is
more frequently made by endoscopy. This procedure
is done by a gastroenterologist (a specialist in digestive
diseases). During an endoscopy the person is given an
intravenous sedative and a small tube is inserted
through the mouth, then into the esophagus and
stomach where the doctor can visualize the hernia.
The procedure takes about 30 minutes and usually
causes no discomfort. It is done on an outpatient basis.

Treatment
Once an abdominal hernia occurs it tends to
increase in size. Some patients with abdominal hernias
wait and watch for a while prior to choosing surgery.
In these cases, they must avoid strenuous physical
activity such as heavy lifting or straining with constipation. They may also wear a truss, which is a support
worn like a belt to keep a small hernia from protruding. People can tell if their hernia is getting worse
if they develop severe constant pain, nausea and vomiting, or if the bulge does not return to normal when
lying down or when they try to gently push it back in
place. In these cases they should consult with their
doctor immediately. But, ultimately, surgery is the
treatment in almost all cases.
There are risks to not repairing a hernia surgically.
Left untreated, a hernia may become incarcerated,
1797

Hernia

and, depending on the location, the hernia is given a
different name.

Hernia

puncture wound. Several small punctures are made to
allow surgical instruments to be inserted. This type of
surgery avoids a larger incision.
A hiatal hernia is treated differently. Medical
treatment is preferred. Treatments include:

An illustration of an epigastric (abdominal) hernia in an adult
male. The torso is shown with its skin removed. Epigastric
hernia is caused commonly by a congenital weakness in
muscles of the central upper abdomen; the intestine bulges
out through the muscle at a point between the navel and
breastbone. (Photograph by John Bavosi, Photo Researchers,
Inc. Reproduced by permission.)



avoiding reclining after meals



avoiding spicy foods, acidic foods, alcohol, and
tobacco



eating small, frequent, bland meals



eating a high-fiber diet.

There are also several types of medications that
help to manage the symptoms of a hiatal hernia.
Antacids are used to neutralize gastric acid and
decrease heartburn. Drugs that reduce the amount of
acid produced in the stomach (H2 blockers) are also
used. This class of drugs includes famotidine (sold
under the name Pepcid), cimetidine (Tagamet), and
ranitidine (Zantac). Omeprazole (Prilosec) is not an
H2 blocker, but is another drug that suppresses gastric
acid secretion and is used for hiatal hernias. Another
option may be metoclopramide (Reglan), a drug that
increases the tone of the muscle around the esophagus
and causes the stomach to empty more quickly.

Alternative treatment
which means it can no longer be reduced or pushed
back into place. With an incarcerated hernia the intestines become trapped outside the abdomen. This could
lead to a blockage in the intestine. If it is severe enough
it may cut off the blood supply to the intestine and part
of the intestine might actually die.
When the blood supply is cut off, the hernia is
termed ‘‘strangulated.’’ Because of the risk of tissue
death (necrosis) and gangrene, and because the hernia
can block food from moving through the bowel, a
strangulated hernia is a medical emergency requiring
immediate surgery. Repairing a hernia before it
becomes incarcerated or strangulated is much safer
than waiting until complications develop.
Surgical repair of a hernia is called a herniorrhaphy. The surgeon will push the bulging part of the
intestine back into place and sew the overlying muscle
back together. When the muscle is not strong enough,
the surgeon may reinforce it with a synthetic mesh.
Surgery can be done on an outpatient basis. It
usually takes 30 minutes in children and 60 minutes
in adults. It can be done under either local or general
anesthesia and is frequently done with a laparoscope.
In this type of surgery, a tube that allows visualization
of the abdominal cavity is inserted through a small
1798

There are alternative therapies for hiatal hernia.
Visceral manipulation, done by a trained therapist,
can help replace the stomach to its proper positioning.
Other options in addition to H2 blockers are available
to help regulate stomach acid production and balance.
One of them, deglycyrrhizinated licorice (DGL), helps
balance stomach acid by improving the protective
substances that line the stomach and intestines and by
improving blood supply to these tissues. DGL does
not interrupt the normal function of stomach acid.
As with traditional therapy, dietary modifications
are important. Small, frequent meals will keep pressure down on the esophageal sphincter. Also, raising
the head of the bed several inches with blocks or books
can help with both the quality and quantity of sleep.

Prognosis
Abdominal hernias generally do not recur in
children but can recur in up to 10% of adult patients.
Surgery is considered the only cure, and the prognosis
is excellent if the hernia is corrected before it becomes
strangulated.
Hiatal hernias are treated successfully with
medication and diet modifications 85% of the time.
GALE ENCYCLOPEDIA OF MEDICINE

Endoscopy—A diagnostic procedure in which a
tube is inserted through the mouth, into the esophagus and stomach. It is used to visualize various
digestive disorders, including hiatal hernias.
Herniorrhaphy—Surgical repair of a hernia.
Incarcerated hernia—A hernia that can not be
reduced, or pushed back into place inside the
intestinal wall.
Reducible hernia—A hernia that can be gently
pushed back into place or that disappears when
the person lies down.
Strangulated hernia—A hernia that is so tightly
incarcerated outside the abdominal wall that the
intestine is blocked and the blood supply to that
part of the intestine is cut off.

The prognosis remains excellent even if surgery is
required in adults who are in otherwise good health.

Prevention

bulge out of place. Hernias may result from a genetic
predisposition toward this weakness. They can also be
the result of weakening the muscle through improper
exercise or poor lifting techniques. Both children
and adults get hernias. Some are painful, while others
are not.
There are three levels of hernias. An uncomplicated hernia is one where the intestines bulge into the
peritoneum (the membrane lining the abdomen), but
they can still be manipulated back into the body
(although they don’t stay in place without corrective
surgery). This is termed a reducible hernia.
If the intestines bulge through the hernia defect
and become trapped, this is called an incarcerated
hernia. If the blood supply to an incarcerated hernia
is shut off, the hernia is called a strangulated hernia.
Strangulated hernias can result in gangrene.
Both incarcerated and strangulated hernias are
medical emergencies and require emergency surgery
to correct. For this reason, doctors generally recommend the repair of an uncomplicated hernia, even if it
causes no discomfort to the patient.

Precautions

Some hernias can be prevented by maintaining a
reasonable weight, avoiding heavy lifting and constipation, and following a moderate exercise program to
maintain good abdominal muscle tone.
Resources
BOOKS

Bare, Brenda G., and Suzanne C. Smeltzer. Brunner and
Suddarth’s Textbook of Medical-Surgical Nursing.
8th ed. Philadelphia: Lippincott-Raven Publishers, 1996.

Joyce S. Siok, RN

Hernia repair
Definition
Hernia repair is a surgical procedure to return an
organ that protrudes through a weak area of muscle to
its original position.

Purpose
Hernias occur when a weakness in the wall of the
abdomen allows an organ, usually the intestines, to
GALE ENCYCLOPEDIA OF MEDICINE

Hernia repair can be performed under local,
regional, or general anesthesia. The choice depends
on the age and health of the patient and the type of
hernia. Generally hernia repair is very safe surgery,
but—as with any surgery—the risk of complications
increases if the patient smokes, is obese, is very
young or very old, uses alcohol heavily, or uses illicit
drugs.

Description
Hernia repairs are performed in a hospital or
outpatient surgical facility by a general surgeon.
Depending on the patient’s age, health, and the type
of hernia, patients may be able to go home the same
day or may remain hospitalized for up to three to
five days.
There are two types of hernia repair. A herniorrhaphy is used for simpler hernias. The intestines are
returned to their proper place and the defect in the
abdominal wall is mended. A hernioplasty is used for
larger hernias. In this procedure, plastic or steel mesh
is added to the abdominal wall to repair and reinforce
the weak spot.
There are five kinds of common hernia repairs.
They are named for the part of the body closest to the
hernia, or bulge.
1799

Hernia repair

KEY TERMS

Hernia repair

Hernia

Penis

Intestinal hernia

Sutures

Testicle

In this inguinal hernia repair, an incision is made in the abdomen. The hernia is located, and the intestines are returned to the
abdomen. The abdominal wall is then sutured together to close any space and reinforce the weak area. (Illustration by Electronic
Illustrators Group.)

Femoral hernia repair
This procedure repairs a hernia that occurs in the
groin where the thigh meets the abdomen. It is called a
femoral hernia repair because it is near the spot where
the femoral artery and vein pass from the leg into the
trunk of the body. Sometimes this type of hernia
creates a noticeable bulge.
An incision is made in the groin area. The tissues
are separated from the hernia sac, and the intestines
are returned to the abdomen. The area is often reinforced with webbing before it is sewn shut. The skin is
closed with sutures or metal clips that can be removed
in about one week.
Inguinal hernia repair
Inguinal hernia repair closes a weakness in the
abdominal wall that is near the inguinal canal, the spot
where the testes descend from the body into the scrotum.
This type of hernia occurs in about two percent of adult
males.
An incision is made in the abdomen, then the hernia is located and repaired. The surgeon must be alert
not to injure the spermatic cord, the testes, or the blood
supply to the testes. If the hernia is small, it is simply
repaired. If it is large, the area is reinforced with mesh to
prevent a recurrence. External skin sutures can be
removed in about a week. Patients should not resume
sexual activity until being cleared by their doctor.
Umbilical hernia repair
This procedure repairs a hernia that occurs when
the intestines bulge through the abdomen wall near
1800

the navel. Umbilical hernias are most common in
infants.
An incision is made near the navel. The hernia
is located and the intestines are returned to the
abdomen. The peritoneum is closed, then the large
abdominal muscle is pulled over the weak spot in
such a way as to reinforce the area. External sutures
or skin clips can be removed in about 10 days.
Incisional hernia repair
Incisional hernias occur most frequently at the site
of a scar from earlier abdominal surgery. Once again,
the abdomen is opened and the intestines returned to
their proper place. The area is reinforced with mesh,
and the abdominal wall is reconstructed to prevent
another hernia from developing. External sutures can
be removed in about a week.
Hiatal hernia
A hiatal hernia repair is slightly different from the
other hernias described here, because it corrects a
weakness or opening in the diaphragm, the muscle
that separates the chest cavity from the abdominal
cavity. This surgery is done to prevent the stomach
from shifting up into the chest cavity and to prevent
the stomach from spilling gastric juices into the
esophagus, causing pain and scarring.
An incision is made in the abdomen or chest, and
the hole or weakness in the diaphragm is located and
repaired. The top of the stomach is wrapped around
the bottom of the esophagus, and they are sutured
together to hold the stomach in place. Sometimes the
GALE ENCYCLOPEDIA OF MEDICINE

Endoscopy—A procedure in which an instrument
containing a camera is inserted into the gastrointestinal tract so that the doctor can visually inspect
the gastrointestinal system.
Gangrene—Death and decay of body tissue
because the blood supply is cut off. Tissues that
have died in this way must be surgically removed.
Peritoneum—The transparent membrane lining the
abdominal cavity that holds organs such as the
intestines in place.

vagus nerve is cut in order to decrease the amount of
acid the stomach produces. External sutures can be
removed in about one week. This type of hernia repair
often requires a longer hospital stay than the other
types, although techniques are being improved that
reduce invasiveness of the surgery and the length of
the hospital stay.

Preparation
Before the operation, the patient will have blood
and urine collected for testing. X rays are taken of
the affected area. In a hiatal hernia, an endoscopy
(a visual inspection of the organs) is done.
Patients should meet with the anesthesiologist
before the operation to discuss any medications or
conditions that might affect the administration of
anesthesia. Patients may be asked to temporarily
discontinue certain medications. The day of the operation, patients should not eat or drink anything. They
may be given an enema to clear the bowels.

Aftercare
Patients should eat a clear liquid diet until the
gastrointestinal tract begins functioning again.
Normally this is a short period of time. After that,
they are free to eat a healthy, well-balanced diet of
their choice. They may bathe normally, using a gentle,
unscented soap. An antibiotic ointment may be
prescribed for the incision. After the operation, a
hard ridge will form along the incision line. With
time, this ridge softens and becomes less noticeable.
Patients who remain in the hospital will have blood
drawn for follow-up studies.
Patients should begin easy activities, such as walking, as soon as they are comfortable, but should avoid
GALE ENCYCLOPEDIA OF MEDICINE

strenuous exercise for four to six weeks, and especially
avoid heavy lifting. Learning and practicing proper
lifting techniques is an important part of patient education after the operation. Patients may be given a
laxative or stool softener so that they will not strain
to have bowel movements. They should discuss with
their doctor when to resume driving and sexual
activity.

Risks
As with any surgery, there exists the possibility of
excessive bleeding and infection after the surgery. In
inguinal and femoral hernia repair, a slight risk of
damage to the testicles or their blood supply exists
for male patients. Accidental damage may be caused
to the intestinal tract, but generally complications
are few.

Normal results
The outcome of surgery depends on the age and
health of the patient and on the type of hernia.
Although most hernias can be repaired without
complications, hernias recur in 10–20% of people
who have had hernia surgery.
Resources
OTHER

‘‘Hernia Repair.’’ ThriveOnline.
<http://thriveonline.oxygen.com>.

Tish Davidson, A.M.

Herniated disk
Definition
Disk herniation is a rupture of fibrocartilagenous
material (annulus fibrosis) that surrounds the intervertebral disk. This rupture involves the release of the
disk’s center portion containing a gelatinous substance called the nucleus pulposus. Pressure from the
vertebrae above and below may cause the nucleus
pulposus to be forced outward, placing pressure on a
spinal nerve and causing considerable pain and
damage to the nerve. This condition most frequently
occurs in the lumbar region and is also commonly
called herniated nucleus pulposus, prolapsed disk,
ruptured intervertebral disk, or slipped disk.
1801

Herniated disk

KEY TERMS

Herniated disk

Description
The spinal column is made up of 26 vertebrae that
are joined together and permit forward and backward
bending, side bending, and rotation of the spine. Five
distinct regions comprise the spinal column, including
the cervical (neck) region, thoracic (chest) region,
lumbar (low back) region, sacral and coccygeal (tailbone) region. The cervical region consists of seven
vertebrae, the thoracic region includes 12 vertebrae,
and the lumbar region contains five vertebrae. The
sacrum is composed of five fused vertebrae, which
are connected to four fused vertebrae forming the
coccyx. Intervertebral disks lie between each adjacent
vertebra.
Each disk is composed of a gelatinous material in
the center, called the nucleus pulposus, surrounded
by rings of a fiberous tissue (annulus fibrosus). In
disk herniation, an intervertebral disk’s central
portion herniates or slips through the surrounding
annulus fibrosus into the spinal canal, putting pressure on a nerve root. Disk herniation most commonly
affects the lumbar region between the fifth lumbar
vertebra and the first sacral vertebra. However, disk
herniation can also occur in the cervical spine. The
incidence of cervical disk herniation is most common
between the fifth and sixth cervical vertebrae. The
second most common area for cervical disk herniation occurs between the sixth and seventh cervical
vertebrae. Disk herniation is less common in the
thoracic region.
Predisposing factors associated with disk herniation include age, gender, and work environment. The
peak age for occurrence of disk herniation is between
20–45 years of age. Studies have shown that males are
more commonly affected than females in lumbar disk
herniation by a 3:2 ratio. Prolonged exposure to a
bent-forward work posture is correlated with an
increased incidence of disk herniation.
There are four classifications of disk pathology:


A protrusion may occur where a disk bulges without
rupturing the annulus fibrosis.



The disk may prolapse where the nucleus pulposus
migrates to the outermost fibers of the annulus
fibrosis.



There may be a disk extrusion, which is the case if the
annulus fibrosis perforates and material of the
nucleus moves into the epidural space.



The sequestrated disk may occur as fragments from
the annulus fibrosis and nucleus pulposus are outside
the disk proper.

1802

Causes and symptoms
Any direct, forceful, and vertical pressure on the
lumbar disks can cause the disk to push its fluid contents into the vertebral body. Herniated nucleus pulposus may occur suddenly from lifting, twisting, or
direct injury, or it can occur gradually from degenerative changes with episodes of intensifying symptoms.
The annulus may also become weakened over time,
allowing stretching or tearing and leading to a disk
herniation. Depending on the location of the herniation, the herniated material can also press directly on
nerve roots or on the spinal cord, causing a shock-like
pain (sciatica) down the legs, weakness, numbness, or
problems with bowels, bladder, or sexual function.

Diagnosis
Several radiographic tests are useful for confirming
a diagnosis of disk herniation and locating the source
of pain. These tests also help the surgeon indicate the
extent of the surgery needed to fully decompress the
nerve. X rays show structural changes of the lumbar
spine. Myelography is a special x ray of the spine in
which a dye or air is injected into the patient’s spinal
canal. The patient lies strapped to a table as the table
tilts in various directions and spot x rays are taken.
X rays showing a narrowed dye column in the intervertebral disk area indicate possible disk herniation.
Computed tomography scan (CT or CAT scans)
exhibit the details of pathology necessary to obtain
consistently good surgical results. Magnetic resonance
imaging (MRI) analysis of the disks can accurately
detect the early stages of disk aging and degeneration.
Electomyograms (EMGs) measure the electrical activity of the muscle contractions and possibly show
evidence of nerve damage. An EMG is a powerful
tool for assessing muscle fatigue associated with
muscle impairment with low back pain.

Treatment
Drugs
Unless serious neurologic symptoms occur, herniated disks can initially be treated with pain medication and up to 48 hours of bed rest. There is no proven
benefit from resting more than 48 hours. Patients are
then encouraged to gradually increase their activity.
Pain medications, including antiinflammatories,
muscle relaxers, or in severe cases, narcotics, may be
continued if needed.
Epidural steroid injections have been used to
decrease pain by injecting an antiinflammatory drug,
GALE ENCYCLOPEDIA OF MEDICINE

Herniated disk

Spinal cord
Vertebra

Spinal nerve
Disk

A herniated disk refers to the rupture of fibrocartilagenous material, called the annulus fibrosis, that surrounds the intervertebral disk. When this occurs, pressure from the vertebrae above and below may force the disk’s center portion, a gel-like
substance, outward, placing additional pressure on the spinal nerve and causing pain and damage to the nerve. (Illustration by
Electronic Illustrators Group.)

usually a corticosteroid, around the nerve root to
reduce inflammation and edema (swelling). This
partly relieves the pressure on the nerve root as well
as resolves the inflammation.
Physical therapy
Physical therapists are skilled in treating acute
back pain caused by the disk herniation. The physical
therapist can provide noninvasive therapies, such as
ultrasound or diathermy to project heat deep into the
tissues of the back or administer manual therapy, if
mobility of the spine is impaired. They may help
improve posture and develop an exercise program
for recovery and long-term protection. Appropriate
exercise can help take pressure off inflamed nerve
structures, while improving overall posture and flexibility. Traction can be used to try to decrease pressure
on the disk. A lumbar support can be helpful for a
herniated disk at this level as a temporary measure to
reduce pain and improve posture.
GALE ENCYCLOPEDIA OF MEDICINE

Surgery
Surgery is often appropriate for conditions that do
not improve with the usual treatment. In this event, a
strong, flexible spine is important for a quick recovery
after surgery. There are several surgical approaches to
treating a herniated disk, including the classic discectomy, microdiscectomy, or percutanteous discectomy.
The basic differences among these procedures are the
size of the incision, how the disk is reached surgically,
and how much of the disk is removed.
Discectomy is the surgical removal of the portion
of the disk that is putting pressure on a nerve causing
the back pain. In the classic disectomy, the surgeon
first enters through the skin and then removes a bony
portion of the vertebra called the lamina, hence the
term laminectomy. The surgeon removes the disk
material that is pressing on a nerve. Rarely is the entire
lamina or disk entirely removed. Often, only one
side is removed and the surgical procedure is termed
hemi-laminectomy.
1803

Herniated disk

In microdiscectomy, through the use of an operating microscope, the surgeon removes the offending
bone or disk tissue until the nerve is free from
compression or stretch. This procedure is possible
using local anesthesia. Microsurgery techniques vary
and have several advantages over the standard discectomy, such as a smaller incision, less trauma to the
musculature and nerves, and easier identification of
structures by viewing into the disk space through
microscope magnification.
Percutaneous disk excision is performed on an
outpatient basis, is less expensive than other surgical
procedures, and does not require a general anesthesia.
The purpose of percutaneous disk excision is to reduce
the volume of the affected disk indirectly by partial
removal of the nucleus pulposus, leaving all the structures important to stability practically unaffected. In
this procedure, large incisions are avoided by inserting
devices that have cutting and suction capability.
Suction is applied and the disk is sliced and aspirated.
Arthroscopic microdiscectomy is similar to percutaneous discectomy, however it incorporates modified
arthroscopic instruments, including scopes and suction devices. A suction irrigation of saline solution is
established through two entry sites. A video discoscope is introduced from one site and the deflecting
instruments from the opposite side. In this way, the
surgeon is able to search and extract the nuclear fragments under direct visualization.
Laser disk decompression is performed using similar means as percutaneous excision and arthroscopic
microdiscectomy, however laser energy is used to
remove the disk tissue. Here, laser energy is percutanteously introduced through a needle to vaporize a small
volume of nucleus pulposus, thereby dropping the pressure of the disk and decompressing the involved neural
tissues. One disadvantage of this procedure is the high
initial cost of the laser equipment. It is important to
realize that only a very small percentage of people with
herniated lumbar disks go on to require surgery.
Further, surgery should be followed by appropriate
rehabilitation to decrease the chance of reinjury.
Chemonucleolysis
Chemonucleolysis is an alternative to surgical
excision. Chymopapain, a purified enzyme derived
from the papaya plant, is injected percutaneously
into the disk space to reduce the size of the herniated
disks. It hydrolyses proteins, thereby decreasing
water-binding capacity, when injected into the nucleus
pulposus inner disk material. The reduction in size of
the disk relieves pressure on the nerve root.
1804

KEY TERMS
Annulus fibrosis—The outer portion of the intervertebral disk made primarily of fibrocartilage rings.
Epidural space—The space immediately surrounding the outermost membrane of the spinal cord.
Excision—The process of excising, removing, or
amputating.
Fibrocartilage—Cartilage that consists of dense
fibers.
Nucleus pulposus—The center portion of the intervertebral disk that is made up of a gelatinous
substance.
Percutaneous—Performed through the skin.

Spinal fusion
Spinal fusion is the process by which bone grafts
harvested from the iliac crest (thick border of the ilium
located on the pelvis) are placed between the intervertebral bodies after the disk material is removed. This
approach is used when there is a need to reestablish the
normal bony relationship between the vertebrae. A
total discectomy may be needed in some cases because
lumbar spinal fusion can help prevent recurrent
lumbar disk herniation at a particular level.

Alternative treatment
Acupuncture involves the use of fine needles
inserted along the pathway of the pain to move energy
locally and relieve the pain. An acupuncturist determines the location of the nerves affected by the
herniated disk and positions the needles appropriately. Massage therapists may also provide shortterm relief from a herniated disk. Following manual
examination and x-ray diagnosis, chiropractic treatment usually includes manipulation to correct muscle
and joint malfunctions, while care is taken not to place
an additional strain on the injured disk. If a full trial of
conservative therapy fails, or if neurologic problems
(weakness, bowel or bladder problems, and sensory
loss) develop, the next step is usually evaluation by an
orthopedic surgeon.

Prognosis
Only 5–10% of patients with unrelenting sciatica
and neurological involvement, leading to chronic pain
of the lumbar spine, need to have a surgical procedure
performed. This strongly suggests that many patients
GALE ENCYCLOPEDIA OF MEDICINE

Heterotropia see Strabismus

Hiccups

with herniated disks at the lumbar level respond
well to conservative treatment. For those patients
who do require surgery for lumbar disk herniation,
the reviewed procedures of nerve root decompression
caused by disk herniation is favorable. Results of
studies varied from 60–90% success rates. Disk surgery has progressively evolved in the direction of
decreasing invasiveness. Each surgical procedure is
not without possible complications, which can lead
to chronic low back pain and restricted lifestyle.

HFRS see Hantavirus infections

Hiccups
Definition
Hiccups are the result of an involuntary, spasmodic contraction of the diaphragm followed by the
closing of the throat.

Prevention
Proper exercises to strengthen the lower back and
abdominal muscles are key in preventing excess stress
and compressive forces on lumbar disks. Good
posture will help prevent problems on cervical, thoracic, and lumbar disks. A good flexibility program is
critical for prevention of muscle and spasm that can
cause an increase in compressive forces on disks at any
level. Proper lifting of heavy objects is important for
all muscles and levels of the individual disks. Good
posture in sitting, standing, and lying down is helpful
for the spine. Losing weight, if needed, can prevent
weakness and unnecessary stress on the disks caused
by obesity. Choosing proper footwear may also be
helpful to reduce the impact forces to the lumbar
disks while walking on hard surfaces. Wearing special
back support devices may be helpful if heavy lifting is
required with combinations of twisting.
Resources
OTHER

‘‘Back Pain.’’ Healthtouch Online Page.
<http://www.healthtouch.com>.

Jeffrey P. Larson, RPT

Hernioplasty see Hernia repair
Herniorrhaphy see Hernia repair
Herpes see Cold sore
Herpes encephalitis see Encephalitis
Herpes genitalis see Genital herpes
Herpes simplex see Cold sore
Herpes simplex type 2 see Genital herpes
Herpes type 2 see Genital herpes
Herpes zoster infection see Shingles
Heterotopic transplant see Liver
transplantation
GALE ENCYCLOPEDIA OF MEDICINE

Description
Hiccups are one of the most common, but thankfully mildest, disorders to which humans are prey.
Virtually everyone experiences them at some point,
but they rarely last long or require a doctor’s care.
Occasionally, a bout of hiccups will last longer than
two days, earning it the name ‘‘persistent hiccups.’’
Very few people will experience intractable hiccups,
in which hiccups last longer than one month.
A hiccup involves the coordinated action of
the diaphragm and the muscles that close off the
windpipe (trachea). The diaphragm is a domeshaped muscle separating the chest and abdomen,
normally responsible for expanding the chest cavity
for inhalation. Sensation from the diaphragm travels to the spinal cord through the phrenic nerve
and the vagus nerve, which pass through the chest
cavity and the neck. Within the spinal cord, nerve
fibers from the brain monitor sensory information
and adjust the outgoing messages that control contraction. These messages travel along the phrenic
nerve.
Irritation of any of the nerves involved in this loop
can cause the diaphragm to undergo involuntary contraction, or spasm, pulling air into the lungs. When
this occurs, it triggers a reflex in the throat muscles.
Less than a tenth of a second afterward, the trachea is
closed off, making the characteristic ‘‘hic’’ sound.

Causes and symptoms
Hiccups can be caused by central nervous system
disorders, injury or irritation to the phrenic and
vagus nerves, and toxic or metabolic disorders affecting the central or peripheral nervous systems. They
may be of unknown cause or may be a symptom of
psychological stress. Hiccups often occur after drinking carbonated beverages or alcohol. They may also
follow overeating or rapid temperature changes.
1805

High-risk pregnancy

Persistent or intractable hiccups may be caused by
any condition which irritates or damages the relevant
nerves, including:


overstretching of the neck



laryngitis



heartburn (gastroesophageal reflux)



irritation of the eardrum (which is innervated by the
vagus nerve)



general anesthesia



surgery



bloating



tumor



infection



diabetes

Diagnosis
Hiccups are diagnosed by observation, and by hearing the characteristic sound. Diagnosing the cause of
intractable hiccups may require imaging studies,
blood tests, pH monitoring in the esophagus, and
other tests.

Treatment
Most cases of hiccups will disappear on their own.
Home remedies which interrupt or override the
spasmodic nerve circuitry are often effective. Such
remedies include:


holding one’s breath for as long as possible



breathing into a paper bag



swallowing a spoonful of sugar



bending forward from the waist and drinking water
from the wrong side of a glass

Treating any underlying disorder will usually cure
the associated hiccups. Chlorpromazine (Thorazine)
relieves intractable hiccups in 80% of cases.
Metoclopramide (Reglan), carbamazepam, valproic
acid (Depakene), and phenobarbital are also used.
As a last resort, surgery to block the phrenic nerve
may be performed, although it may lead to significant
impairment of respiration.

Prognosis
Most cases of hiccups last no longer than several
hours, with or without treatment.
1806

KEY TERMS
Nerve—Fibers that carry sensory information,
movement stimuli, or both from the brain and
spinal cord to other parts of the body and back
again. Some nerves, including the vagus nerve,
innervate distantly separated parts of the body.

Prevention
Some cases of hiccups can be avoided by drinking
in moderation, avoiding very hot or very cold food,
and avoiding cold showers. Carbonated beverages
when drunk through a straw deliver more gas to the
stomach than when sipped from a container; therefore, avoid using straws.
Resources
BOOKS

Hurst, J. Willis. Medicine for the PracticingPhysician.
Stamford: Appleton & Lange, 1988.

Richard Robinson

High-altitude sickness see Altitude sickness
High blood phosphate level see Phosphorus
imbalance
High blood pressure see Pulmonary
hypertension
High calcium blood level see
Hypercalcemia
High cholesterol see Cholesterol, high
High potassium blood level see
Hyperkalemia

High-risk pregnancy
Definition
A high risk pregnancy is one in which some condition puts the mother, the developing fetus, or both at
higher-than-normal risk for complications during or
after the pregnancy and birth.
GALE ENCYCLOPEDIA OF MEDICINE

A pregnancy can be considered a high-risk pregnancy for a variety of reasons. Factors can be divided
into maternal and fetal. Maternal factors include age
(younger than age 15, older than age 35); weight
(pre-pregnancy weight under 100 lb or obesity); height
(under five feet); history of complications during
previous pregnancies (including stillbirth, fetal loss,
preterm labor and/or delivery, small-for-gestational
age baby, large baby, pre-eclampsia or eclampsia);
more than five previous pregnancies; bleeding during
the third trimester; abnormalities of the reproductive
tract; uterine fibroids; hypertension; Rh incompatability;
gestational diabetes; infections of the vagina and/or
cervix; kidney infection; fever; acute surgical emergency
(appendicitis, gallbladder disease, bowel obstruction);
post-term pregnancy; pre-existing chronic illness (such
as asthma, autoimmune disease, cancer, sickle cell
anemia, tuberculosis, herpes, AIDS, heart disease, kidney
disease, Crohn’s disease, ulcerative colitis, diabetes).
Fetal factors include exposure to infection (especially
herpes simplex, viral hepatitis, mumps, rubella, varicella, syphilis, toxoplasmosis, and infections caused by
coxsackievirus); exposure to damaging medications
(especially phenytoin, folic acid antagonists, lithium,
streptomycin, tetracycline, thalidomide, and warfarin);
exposure to addictive substances (cigarette smoking,
alcohol intake, and illicit or abused drugs). A pregnancy is also considered high-risk when prenatal tests
indicate that the baby has a serious health problem (for
example, a heart defect). In such cases, the mother will
need special tests, and possibly medication, to carry the
baby safely through to delivery. Furthermore, certain
maternal or fetal problems may prompt a physician to
deliver a baby early, or to choose a surgical delivery
(cesarean section) rather than a vaginal delivery.
Most women will see one healthcare provider
during pregnancy, either an obstetrician, a midwife,
or a nurse practitioner. Women who have a medical
problem may need to see a medical specialist as well.
Women diagnosed with a high-risk pregnancy may
also need the expert advice and care of a perinatologist. A perinatologist is a medical doctor (obstetrician) who specializes in the care of women who are at
high risk for having problems during pregnancy.
Perinatologists care for women who have preexisting medical problems as well as women who
develop complications during pregnancy.

Diagnosis
A woman with a high-risk pregnancy will need
closer monitoring than the average pregnant woman.
GALE ENCYCLOPEDIA OF MEDICINE

Such monitoring may include more frequent visits
with the primary caregiver, tests to monitor the
medical problem, blood tests to check the levels
of medication, amniocentesis, serial ultrasound
examination, and fetal monitoring. These tests are
designed to track the original condition, survey for
complications, verify that the fetus is growing
adequately, and make decisions regarding whether
labor may need to be induced to allow for early
delivery of the fetus.

Treatment
Treatment varies widely with the type of disease,
the effect that pregnancy has on the disease, and the
effect that the disease has on pregnancy. Additional
tests may help determine the need for changes in
medication or additional treatment.

Prognosis
The prognosis depends in large part on the specific
medical condition. Some medical conditions make it
difficult to get pregnant and lead to a higher risk of
problems in the baby. An example of this type of condition is thyroid disease. In thyroid disease, the thyroid
gland (located in the neck) may produce too much or
too little thyroid hormone. Abnormal levels of thyroid
hormone can cause problems in pregnancy and affect
the health of the baby. Fortunately, thyroid disease can
be treated with medication. As long as the level of
thyroid hormone is controlled throughout pregnancy,
there should be no problems for mother or baby.
There are many medical conditions that usually
do not interfere with pregnancy, but are themselves
affected by pregnancy. This group includes asthma,
epilepsy, and ulcerative colitis. For example, some
women with ulcerative colitis experience a worsening
of their symptoms during pregnancy, while others will
have no change or may get better during pregnancy.
The same is true of asthma; some women notice that
their asthma symptoms are better during pregnancy,
some find their asthma worse, and some women notice
no change in symptoms during pregnancy. No one
understands why this is so, but due to this unpredictability, all women with chronic illnesses should be
monitored carefully throughout pregnancy.
There is also a group of medical conditions that
can have a major impact on pregnancy. Women with
lupus (disease caused by alterations in the immune
system that result in inflammation of connective tissue
and organs) or kidney disease face real risks during
pregnancy. Pregnancy can cause their symptoms to
1807

High-risk pregnancy

Description

Hirschsprung’s disease

worsen significantly and can lead to serious illness.
Because these diseases can affect the mother’s ability
to supply oxygen and nutrients to the baby through
the placenta, they can cause problems for the baby as
well. These babies may not be able to grow and gain
weight properly (intrauterine growth retardation).
There is also an increased risk of stillbirth.
Diabetes is a medical condition that is both
affected by pregnancy and affects pregnancy. Diabetes
can lead to miscarriages, birth defects, and stillbirths.
When a woman monitors her blood sugar carefully and
treats high levels with insulin, the risk of these negative
outcomes drops a great deal. Unfortunately, pregnancy
makes diabetes much harder to control. In general,
blood sugar and the need for insulin to control it rise
throughout pregnancy.
Most medical conditions do not lead to complications in pregnancy. With frequent visits to healthcare
providers, and careful attention to medication, women
with medical problems usually enjoy healthy, successful pregnancies. There are a few medical conditions
that can cause health risks to both mother and
baby during pregnancy. Women with these medical
problems should consider these risks before deciding
to become pregnant. Many of these women will benefit
from the care of a perinatologist during pregnancy.
Only rarely (in the case of severe heart disease, for
example) are the risks to the mother so high that she
should not consider pregnancy at all.

KEY TERMS
Gestational diabetes—Diabetes of pregnancy leading to increased levels of blood sugar. Unlike diabetes mellitus, gestational diabetes is caused by
pregnancy and goes away when pregnancy ends.
Like diabetes mellitus, gestational diabetes is
treated with a special diet and insulin, if necessary.
Preeclampsia—A disease that only affects pregnant
women. The most common signs and symptoms are
increased blood pressure, swelling in the hands and
feet, and abnormal results on special blood and
urine tests.
Premature labor—Labor beginning before 36 weeks
of pregnancy.

that any medication is adjusted properly to increase
the chance of having a successful pregnancy.
Resources
BOOKS

Beers, Mark H., et al., editors. ‘‘High-Risk Pregnancies.’’ In
The Merck Manual of Diagnosis and Therapy. Rahway,
NJ: Merck Research Laboratories, 2004.

Rosalyn Carson-DeWitt, MD

High sodium blood level see Hypernatremia
Prevention
A pre-pregnancy visit with a healthcare provider is
especially important for a woman who has a medical
problem. The doctor will discuss how women with
this condition usually fare during pregnancy. For
some diseases (such as lupus), pregnancy can mean
increased risk of health problems for mother and baby.
Sometimes, the medication a woman needs to
control a medical condition can cause problems for
the baby. There may be another medication available
that is safer for use in pregnancy. In some cases there is
no other medication, and a woman must weigh the
risks to the baby when deciding whether or not to
become pregnant.
A woman who has not had a pre-pregnancy visit
should contact a healthcare provider as soon as she
learns she is pregnant. Often, the provider will schedule the first prenatal visit within a day or two, instead
of waiting until eight to 10 weeks of pregnancy. This is
because certain medical conditions can increase the
risk of miscarriage. The provider will want to be sure
1808

Hindu medicine see Ayurvedic medicine
Hip bath see Sitz bath
Hip replacement see Joint replacement

Hirschsprung’s disease
Definition
Hirschsprung’s disease, also known as congenital
megacolon or aganglionic megacolon, is an abnormality in which certain nerve fibers are absent in segments of the bowel, resulting in severe bowel
obstruction. It was first identified in 1886 by a physician named Harold Hirschsprung.

Description
Hirschsprung’s disease is caused when certain
nerve cells (called parasympathetic ganglion cells) in
GALE ENCYCLOPEDIA OF MEDICINE

Hirschprung’s disease occurs once in every 5,000
live births, and it is about four times more common in
males than females. Between 4% and 50% of siblings
are also afflicted. The wide range for recurrence is due
to the fact that the recurrence risk depends on the
gender of the affected individual in the family (i.e., if
a female is affected, the recurrence risk is higher)
and the length of the aganglionic segment of the
colon (i.e., the longer the segment that is affected, the
higher the recurrence risk).

Causes and symptoms
Hirschsprung’s disease occurs early in fetal development when, for unknown reasons, there is either
failure of nerve cell development, failure of nerve cell
migration, or arrest in nerve cell development in a
segment of the bowel. The absence of these nerve
fibers, which help control the movement of bowel
contents, is what results in intestinal obstruction
accompanied by other symptoms.
There is a genetic basis to Hirschsprung’s disease,
and it is believed that it may be caused by different
genetic factors in different subsets of families. Proof
that genetic factors contribute to Hirschprung’s
disease is that it is known to run in families, and it
has been seen in association with some chromosome
abnormalities. For example, about 10% of children
with the disease have Down syndrome (the most
common chromosomal abnormality). Molecular
diagnostic techniques have identified many genes
that cause susceptibility to Hirschprung’s disease. As
of the early 2000s, a total of six genes have been
identified: the RET gene, the glial cell line-derived
neurotrophic factor gene, the endothelin-B receptor
gene, endothelin converting enzyme, the endothelin-3
gene, and the Sry-related transcription factor SOX10.
Mutations that inactivate the RET gene are the
most frequent, occurring in 50% of familial cases
(cases which run in families) and 15–20% of sporadic
(non-familial) cases. Mutations in these genes do not
GALE ENCYCLOPEDIA OF MEDICINE

cause the disease, but they make the chance of developing it more likely. Mutations in other genes or
environmental factors are required to develop the
disease, and these other factors are not understood.
As of 2004, at least three chromosomes are known to
be involved: 13q22, 21q22, and 10q. Hirschsprung’s
disease has also been reported in association with
abnormal forms of chromosome 18.
For persons with a ganglion growth beyond the
sigmoid segment of the colon, the inheritance pattern
is autosomal dominant with reduced penetrance (risk
closer to 50%). For persons with smaller segments
involved, the inheritance pattern is multifactorial
(caused by an interaction of more than one gene and
environmental factors, risk lower than 50%) or autosomal recessive (one disease gene inherited from each
parent, risk closer to 25%) with low penetrance.
The initial symptom is usually severe, continuous
constipation. A newborn may fail to pass meconium
(the first stool) within 24 hours of birth, may repeatedly vomit yellow- or green-colored bile and may
have a distended (swollen, uncomfortable) abdomen.
Occasionally, infants may have only mild or intermittent constipation, often with diarrhea.
While two-thirds of cases are diagnosed in the
first three months of life, Hirschsprung’s disease may
also be diagnosed later in infancy or childhood.
Occasionally, even adults are diagnosed with a variation of the disease. In older infants, symptoms and
signs may include anorexia (lack of appetite or inability to eat), lack of the urge to move the bowels or
empty the rectum on physical examination, distended
abdomen, and a mass in the colon that can be felt
by the physician during examination. It should be
suspected in older children with abnormal bowel
habits, especially a history of constipation dating
back to infancy and ribbon-like stools.
Occasionally, the presenting symptom may be a
severe intestinal infection called enterocolitis, which is
life-threatening. The symptoms are usually explosive,
watery stools and fever in a very ill-appearing infant.
It is important to diagnose the condition before the
intestinal obstruction causes an overgrowth of bacteria
that evolves into a medical emergency. Enterocolitis can
lead to severe diarrhea and massive fluid loss, which
can cause death from dehydration unless surgery is
done immediately to relieve the obstruction.
Hirschsprung’s disease sometimes occurs in children with other disorders of the autonomic nervous
system, such as congenital central hypoventilation
syndrome, a breathing disorder. Other syndromes associated with Hirschsprung disease include congenital
1809

Hirschsprung’s disease

the wall of the large intestine (colon) do not develop
before birth. Without these nerves, the affected segment of the colon lacks the ability to relax and move
bowel contents along. This causes a constriction and
as a result, the bowel above the constricted area dilates
due to stool becoming trapped, producing megacolon
(dilation of the colon). The disease can affect varying
lengths of bowel segment, most often involving the
region around the rectum. In up to 10% of children,
however, the entire colon and part of the small intestine are involved. This condition is known as total
colonic aganglionosis, or TCA.

Hirschsprung’s disease

deafness and Waardenburg syndrome, a genetic disorder characterized by facial abnormalities and the
loss of normal pigmentation in the hair, skin, and the
iris of the eye.

Diagnosis
Hirschsprung’s disease in the newborn must be
distinguished from other causes of intestinal obstruction. The diagnosis is suspected by the child’s medical
history and physical examination, especially the rectal
exam. The diagnosis is confirmed by a barium enema
x ray, which shows a picture of the bowel. The x ray
will indicate if a segment of bowel is constricted, causing dilation and obstruction. A biopsy of rectal tissue
will reveal the absence of the nerve fibers. Adults may
also undergo manometry, a balloon study (device used
to enlarge the anus for the procedure) of internal anal
sphincter pressure and relaxation.

Treatment
Hirschsprung’s disease is treated surgically. The
goal is to remove the diseased, nonfunctioning segment of the bowel and restore bowel function. This is
often done in two stages. The first stage relieves the
intestinal obstruction by performing a colostomy. This
is the creation of an opening in the abdomen (stoma)
through which bowel contents can be discharged into
a waste bag. When the child’s weight, age, or condition
is deemed appropriate, surgeons close the stoma,
remove the diseased portion of bowel, and perform a
‘‘pull-through’’ procedure, which repairs the colon
by connecting functional bowel to the anus. The pullthrough operation usually establishes fairly normal
bowel function.
Children with total colonic aganglionosis occasionally fail to benefit from a pull-through procedure.
One option in treating these patients is the construction of an ileoanal S-pouch.
The surgeon may recommend a permanent ostomy
if the child has Down syndrome in addition to
Hirschsprung disease, as these children usually have
more difficulty with bowel control.

Prognosis
Overall, prognosis is very good. Most infants with
Hirschsprung’s disease achieve good bowel control
after surgery, but a small percentage of children may
have lingering problems with soilage or constipation.
These infants are also at higher risk for an overgrowth
of bacteria in the intestines, including subsequent
1810

KEY TERMS
Anus—The opening at the end of the intestine that
carries waste out of the body
Barium enema x ray—A procedure that involves
the administration of barium into the intestines by
a tube inserted into the rectum. Barium is a chalky
substance that enhances the visualization of the
gastrointestinal tract on x ray.
Colostomy—The creation of an artificial opening
into the colon through the skin for the purpose of
removing bodily waste. Colostomies are usually
required because key portions of the intestine
have been removed.
Enterocolitis—Severe inflammation of the intestines that affects the intestinal lining, muscle,
nerves and blood vessels.
Manometry—A balloon study of internal anal
sphincter pressure and relaxation.
Meconium—The first waste products to be discharged from the body in a newborn infant, usually
greenish in color and consisting of mucus, bile and
so forth.
Megacolon—Dilation of the colon.
Parasympathetic ganglion cell—Type of nerve cell
normally found in the wall of the colon.

episodes of enterocolitis, and should be closely
followed by a physician. Mortality from enterocolitis
or surgical complications in infancy is 25–30%.

Prevention
Hirschsprung’s disease is a congenital abnormality that has no known means of prevention. It is
important to diagnose the condition early in order to
prevent the development of enterocolitis. Genetic
counseling can be offered to a couple with a previous
child with the disease or to an affected individual
considering pregnancy to discuss recurrence risks
and treatment options. Prenatal diagnosis is not
available as of the early 2000s.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Congenital Anomalies.’’ Section 19, Chapter 261 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
GALE ENCYCLOPEDIA OF MEDICINE

Chen, M. L., and T. G. Keens. ‘‘Congenital Central
Hypoventilation Syndrome: Not Just Another Rare
Disorder.’’ Paediatric Respiratory Reviews 5
(September 2004): 182–189.
Lal, D. R., P. F. Nichol, B. A. Harms, et al. ‘‘Ileo-Anal
S-Pouch Reconstruction in Patients with Total Colonic
Aganglionosis after Failed Pull-Through Procedure.’’
Journal of Pediatric Surgery 39 (July 2004): e7–e9.
Martucciello, G., et al. ‘‘Pathogenesis of Hirschprung’s
Disease.’’ Journal of Pediatric Surgery 35 (2000):
1017–1025.
Munnes, M., et al. ‘‘Familial Form of Hirschprung
Disease: Nucleotide Sequence Studies Reveal Point
Mutations in the RET Proto-oncogene in Two of
Six Families But Not in Other Candidate Genes.’’
American Journal of Medical Genetics 94 (2000):
19–27.
Neville, Holly, MD, and Charles S. Cox, Jr., MD.
‘‘Hirschsprung Disease.’’ eMedicine July15, 2003.
<http://www.emedicine.com/ped/topic1010.htm>.
Prabhakara, K., H. E. Wyandt, X. L. Huang, et al.
‘‘Recurrent Proximal 18p Monosomy and 18q Trisomy
in a Family with a Maternal Pericentric Inversion of
Chromosome 18.’’ Annales de ge´ne´tique 47
(July-September 2004): 297–303.
ORGANIZATIONS

American Pseudo-Obstruction & Hirschsprung’s Society.
158 Pleasant St., North Andover, MA 01845.
(978)685-4477.
National Organization for Rare Disorders (NORD).
55 Kenosia Avenue, P. O. Box 1968, Danbury, CT
06813-1968. (203) 744-0100. Fax: (203) 798-2291.
<http://www.rarediseases.org>.
Pull-thru Network. 316 Thomas St., Bessemer, AL 35020.
(205) 428-5953.

Amy Vance, MS, CGC
Rebecca J. Frey, PhD

over-production of male hormones (androgens), medication, or disease, can cause it to appear at any age.
Women who have hirsutism usually have irregular
menstrual cycles. They sometimes have small breasts
and deep voices, and their muscles and genitals may
become larger than women without the condition.
Types of hirsutism
Idiopathic hirsutism is probably hereditary,
because there is usually a family history of the disorder. Women with idiopathic hirsutism have normal
menstrual cycles and no evidence of any of the conditions associated with secondary hirsutism.
Secondary hirsutism is most often associated with
polycystic ovary syndrome (an inherited hormonal
disorder characterized by menstrual irregularities,
biochemical abnormalities, and obesity). This type of
hirsutism may also be caused by:


malfunctions of the pituitary or adrenal glands



use of male hormones or minoxidil (Loniten), a drug
used to widen blood vessels



adrenal or ovarian tumors.

Causes and symptoms
Hirsutism is rarely caused by a serious underlying
disorder. Pregnancy occasionally stimulates its development. Hirsutism triggered by tumors is very unusual.
Hair follicles usually become enlarged, and the
hairs themselves become larger and darker. A woman
whose hirsutism is caused by an increase in male hormones has a pattern of hair growth similar to that of a
man. A woman whose hirsutism is not hormone-related
has long, fine hairs on her face, arms, chest, and back.

Diagnosis

Hirsutism
Definition
Excessive growth of facial or body hair in women
is called hirsutism.

Description
Hirsutism is not a disease. The condition usually
develops during puberty and becomes more pronounced
as the years go by. However, an inherited tendency,
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis is based on a family history of hirsutism, a personal history of menstrual irregularities, and
masculine traits. Laboratory tests are not needed to
assess the status of patients whose menstrual cycles are
normal and who have mild, gradually progressing
hirsutism.
A family physician or endocrinologist may order
blood tests to measure hormone levels in women with
long-standing menstrual problems or more severe
hirsutism. Computed tomography scans (CT scans) are
sometimes performed to evaluate diseases of the adrenal
glands. Additional diagnostic procedures may be used
to confirm or rule out underlying diseases or disorders.
1811

Hirsutism

PERIODICALS

Histiocytosis X

Histiocytosis X

KEY TERMS
Idiopathic—A term for a disease with no known
cause, from the Greek stems idio (peculiar or separate) and pathy (disease).

Treatment
Primary hirsutism can be treated mechanically.
Mechanical treatment involves bleaching or physically
removing unwanted hair by:


cutting



electrolysis



shaving



tweezing



waxing



using hair-removing creams (depilatories)

Histiocytosis X is a generic term that refers to an
increase in the number of histiocytes, a type of white
blood cell, that act as scavengers to remove foreign
material from the blood and tissues. Since recent
research demonstrated Langerhan cell involvement
as well as histiocytes, this led to a proposal that the
term Langerhans Cell Histiocytosis (LCH) be used
in place of histiocytosis X. Either term refers to
three separate illnesses (listed in order of increasing
severity): eosinophilic granuloma, Hand-SchullerChristian disease and Letterer-Siwe disease.

Description

Low-dose dexamethasone (a synthetic adrenocortical steroid), birth-control pills, or medications that
suppress male hormones (for example, spironolactone) may be prescribed for patients whose condition
stems from high androgen levels.
Treatment of secondary hirsutism is determined
by the underlying cause of the condition.

Prognosis
Birth-control pills alone cause this condition to
stabilize in one of every two patients and to improve in
one of every 10.
When spironolactone (Aldactone) is prescribed to
suppress hair growth, 70% of patients experience
improvement within six months. When women also
take birth-control pills, menstrual cycles become
regular and hair growth is suppressed even more.
Resources
ORGANIZATIONS

American Society for Reproductive Medicine. 1209
Montgomery Highway, Birmingham, AL 35216-2809.
(205) 978-5000. <http://www.asrm.com>.

Maureen Haggerty

Hispanic American health see Minority health
Histamine see Antiulcer drugs
Histamine headache see Cluster headache
1812

Definition

Epidermal (skin) Langerhans cells (a form of
dendritic cell) accumulate with other immune cells in
various parts of the body and cause damage by the
release of chemicals. Normally, Langerhans cells recognize foreign material, including bacteria, and stimulate
the immune system to react to them. Langerhans cells
are usually found in skin, lymph nodes, lungs, and the
gastrointestinal tract. Under abnormal conditions these
cells affect skin, bone, and the pituitary gland as well as
the lungs, intestines, liver, spleen, bone marrow, and
brain. Therefore, the disease is not confined to areas
where Langerhans cells are normally found. The
disease is more common in children than adults and
tends to be most severe in very young children.
Histiocytosis X or LCH is a family of related conditions characterized by a distinct inflammatory and
proliferative process but differs from each other in
which parts of the body are involved. The least severe
of the histiocytosis X/LCH family is eosinophilic
granuloma. Approximately 60–80% of all diagnosed
cases are in this classification, which usually occurs in
children aged 5–10 years. The bones are involved
50–75% of the time, which includes the skull or mandible, and the long bones. If the bone marrow is involved,
anemia can result. With skull involvement, growths
can occur behind the eyes, bulging them forward.
One recent case study involved swelling of the eyes
caused by histiocytosis in a three-year-old girl. The
lungs are involved less than 10% of the time, and this
involvement signals the worst prognosis.
Next in severity is Hand-Schuller-Christian disease, a chronic, scattered form of histiocytosis. It occurs
most commonly from the age of one to three years and
is a slowly progressive disease that affects the softened
areas of the skull, other flat bones, the eyes, and skin.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anemia—Abnormally low level of red blood cells
in the blood.
Biopsy—Surgical removal of tissue for examination.

Causes and symptoms

CT or CAT—Computed tomography, a radiologic
imaging that uses computer processing to generate
an image of tissue density in slices through the
patient’s body.
Cytokines—The term used to include all protein
messengers that regulate immune responses.

This is a rare disorder affecting approximately
1 in 200,000 children or adults each year. The
International Histiocyte Society formed a registry in
2000 that has registered a total of 274 adults from 13
countries as of 2003. Because histiocytic disorders are
so rare, little research has been done to determine their
cause. Over time, histiocytosis may lessen in its assault
on the body but there are still problems from damage
to the tissues. There are no apparent inheritance
patterns in these diseases with the exception of a
form involving the lymphatic system; of the 274 adults
in the international registry, only one came from a
family with a history of the disease.

Dendritic—Branched like a tree.
Eosinophils—A leukocyte with coarse, round granules present.
Epidermal—The outermost layer of the skin.
Inflammatory—A localized protective response of
the body caused by injury or destruction of tissues.
MRI—Magnetic resonance imaging, a noninvasive
nuclear procedure that uses electromagnetic energy
to create images of structures inside the body.
Pituitary gland—The master gland located in the
middle of the head that controls the endocrine
glands and affects most bodily functions.
Prostaglandins—A group of nine naturally occurring chemicals in the body that affect smooth
muscles.

The symptoms of histiocytosis are caused by
substances called cytokines and prostaglandins,
which are normally produced by histiocytes and act
as messengers between cells. When these chemicals are
produced in excess amounts and in the wrong places,
they cause tissue swelling and abnormal growth. Thus,
symptoms may include painful lumps in the skull
and limbs as well as rashes on the skin. General
symptoms may include: poor appetite, failure to gain
weight, recurrent fever, and irritability. Symptoms
from other possible sites of involvement include:


gums: swelling, usually without significant discomfort



ear: chronic discharge



liver or spleen: abdominal discomfort or swelling



pituitary: This gland at the base of the brain is
affected at some stage in approximately 20%–30%
of children causing a disturbance in water balance to
produce thirst and frequent urination.



eyes: Due to the bony disease, behind-the-eye bulging may occur (exophthalmos)



lungs: breathing problems

Diagnosis
The diagnosis can be made only by performing a
biopsy, that is, taking a tissue sample under anesthesia
from a site in the patient thought to be involved. Blood
and urine tests, chest and other x rays, magnetic resonance imaging (MRI) and computed tomography scans
(CAT scans) (to check the extent of involvement), and
GALE ENCYCLOPEDIA OF MEDICINE

Serous—Thin and watery, like serum.

possibly bone marrow or breathing tests may be
required to confirm the diagnosis.

Treatment
Although this disease is not cancer, most patients
diagnosed with it are treated in cancer clinics. There
are two reasons for this:


Historically, cancer specialists treated it before the
cause was known.



The treatment requires the use of drugs typically
required to treat cancer.

Any cancer drugs utilized are usually given in smaller doses, which diminishes the severity of their side
effects. Radiation therapy is rarely used, and special
drugs may be prescribed for skin symptoms. If there is
only one organ affected, steroids may be injected
locally, or a drug called indomethacin may be used.
Indomethacin is an anti-inflammatory medication
1813

Histiocytosis X

Letterer-Siwe disease is the acute form of this series of
diseases. It is generally found from the time of birth to
one year of age. It causes an enlarged liver, bruising and
skin lesions, anemia, enlarged lymph glands, other
organ involvement, and extensive skull lesions.

Histoplasmosis

that may achieve a similar response with less severe
side effects.

Histoplasmosis
Definition

Prognosis
The disease fluctuates markedly. If only one
system is involved, the disease often resolves by itself.
Multisystem disease usually needs treatment although
it may disappear spontaneously. The disease is not
normally fatal unless organs vital to life are damaged.
In general, the younger the child at diagnosis and the
more organs involved, the poorer the outlook. If the
condition resolves, there could still be long-term
complications because of the damage done while the
disease was active.

Histoplasmosis is an infectious disease caused by
inhaling the microscopic spores of the fungus
Histoplasma capsulatum. The disease exists in three
forms. Acute or primary histoplasmosis causes flulike symptoms. Most people who are infected recover
without medical intervention. Chronic histoplasmosis
affects the lungs and can be fatal. Disseminated
histoplasmosis affects many organ systems in the
body and is often fatal, especially to people with
acquired immunodeficiency syndrome (AIDS).

Description

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Histiocytic Syndromes.’’ Section 11, Chapter 137 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Behrman, Richard E., Robert Kliegman, and Hal B. Jenson,
editors.Nelson Textbook of Pediatrics. Philadelphia:
W. B. Saunders, 2000.
PERIODICALS

Arico, M., M. Girschikofsky, T. Genereau, et al.
‘‘Langerhans Cell Histiocytosis in Adults. Report from
the International Registry of the Histiocyte Society.’’
European Journal of Cancer 39 (November 2003):
2341–2348.
Eckhardt, A., and A. Schulze. ‘‘Maxillofacial
Manifestations of Langerhans Cell Histiocytosis: A
Clinical and Therapeutic Analysis of 10 Patients.’’ Oral
Oncology 39 (October 2003): 687–694.
Kobyahsi, M., O. Yamamoto, Y. Suenaga, and M. Asahi.
‘‘Electron Microscopic Study of Langerhans Cell
Histiocytosis.’’ Journal ofDermatology July 27,
2000: 453–7.
Levy, J., T. Monos, J.Kapelushnik, et al. ‘‘Langerhans Cell
Histiocytosis with Periorbital Cellulitis.’’ American
Journal of Ophthalmology 136 (November 2003):
939–942.

Histoplasmosis is an airborne infection. The
spores that cause this disease are found in soil that
has been contaminated with bird or bat droppings.
In the United States, the disease is most common in
eastern and midwestern states and is widespread in the
upper Mississippi, Ohio, Missouri, and St. Lawrence
river valleys. Sometimes histoplasmosis is called
Ohio Valley disease, Central Mississippi River Valley
disease, Appalachian Mountain disease, Darling’s
disease, or Histoplasma capsulatum infection.
Anyone can get histoplasmosis, but people who
come in contact with bird and bat excrement are more
likely to be infected. This includes farmers, gardeners,
bridge inspectors and painters, roofers, chimney
cleaners, demolition and construction workers, people
installing or servicing heating and air conditioning
units, people restoring old or abandoned buildings,
and people who explore caves.
The very young and the elderly, especially if they
have a pre-existing lung disease or are heavy smokers,
are more likely to develop symptoms that are more
severe. People who have a weakened immune system,
either from diseases such as AIDS or leukemia, or as
the result of medications they take (corticosteroids,
chemotherapy drugs), are more likely to develop
chronic or disseminated histoplasmosis.

ORGANIZATIONS

Histiocytosis Association of America. 302 North Broadway,
Pitman, NJ 08071. (800) 548–2758 (USA and Canada).
<http://www.histio.org>.
OTHER

‘‘Immunity Disorders.’’ NurseMinerva. June 26, 2001.
<http://nurseminerva.co.uk/immunity.htm>.

Linda K. Bennington, CNS
Rebecca J. Frey, PhD
1814

Causes and symptoms
When the spores of H. capsulatum are inhaled,
they lodge in the lungs where they divide and cause
lesions. This is known as acute or primary histoplasmosis. It is not contagious.
Many otherwise healthy people show no symptoms
of infection at all. When symptoms do occur, they appear
3–17 days after exposure (average time is 10 days).
GALE ENCYCLOPEDIA OF MEDICINE

In some people, the spores that cause the disease
continue to live in the lungs. In about 5% of people
who are infected, usually those with chronic lung
disease, diabetes mellitis, or weakened immune
systems, the disease progresses to chronic histoplasmosis. This can take months or years. Symptoms of
chronic histoplasmosis resemble those of tuberculosis.
Cavities form in the lung tissue, parts of the lung may
collapse, and the lungs fill with fluid. Chronic histoplasmosis is a serious disease that can result in death.
The rarest form of histoplasmosis is disseminated
histoplasmosis. Disseminated histoplasmosis is seen
almost exclusively in patients with AIDS or other
immune defects. In disseminated histoplasmosis the
infection may move to the spleen, liver, bone marrow,
or adrenal glands. Symptoms include a worsening of
those found in chronic histoplasmosis, as well as
weight loss, diarrhea, the development of open sores
in the mouth and nose, and enlargement of the spleen,
liver, and adrenal gland.

Diagnosis
A simple skin test similar to that given for tuberculosis will tell if a person has previously been infected
by the fungus H. capsulatum. Chest x rays often show
lung damage caused by the fungus, but do not lead to a
definitive diagnosis because the damage caused by
other diseases has a similar appearance on the x ray.
Diagnosis of chronic or disseminated histoplasmosis
can be made by culturing a sample of sputum or other
body fluids in the laboratory to isolate the fungus.
The urine, blood serum, washings from the lungs, or
cerebrospinal fluid can all be tested for the presence of
an antigen produced in response to the infection. Most
cases of primary histoplasmosis go undiagnosed.

Treatment
Acute primary histoplasmosis generally requires
no treatment other than rest. Non-prescription drugs
such as acetaminophen (Tylenol) may be used to treat
pain and relieve fever. Avoiding smoke and using a
cool air humidifier may ease chest pain.
Patients with an intact immune system who
develop chronic histoplasmosis are treated with the
GALE ENCYCLOPEDIA OF MEDICINE

drug ketoconazole (Nizoral) or amphotericin B
(Fungizone). Patients with suppressed immune systems are treated with amphotericin B, which is given
intravenously. Because of its potentially toxic side
effects, hospitalization is often required. The patient
may also receive other drugs to minimize the side
effects of the amphotericin B.
Patients with AIDS must continue to take the
drug itraconazole (Sporonox) orally for the rest of
their lives in order to prevent a relapse. If the patient
can not tolerate itraconazole, the drug fluconazole
(Diflucan) can be substituted.

Alternative treatment
In non-immunocompromised patients, alternative therapies can be very successful. Alternative treatment for fungal infections focuses on creating an
environment where the fungus cannot survive. This is
accomplished by maintaining good health and eating a
diet low in dairy products, sugars, including honey
and fruit juice, and foods like beer that contain yeast.
This is complemented by a diet high in raw food.
Supplements of antioxidant vitamins C, E, and A,
along with B complex, may also be added to the diet.
Lactobacillus acidophilus and Bifidobacteria will
replenish the good bacteria in the intestines.
Antifungal herbs, like garlic, can be consumed in
relatively large does and for an extended period of
time in order to be most effective.

Prognosis
Most people recover from primary histoplasmosis
in a few weeks without medical intervention. Patients
with chronic histoplasmosis who are treated with
antifungal drugs generally recover rapidly if they do
not have an underlying serious disease. When left
untreated, or if serious disease is present, histoplasmosis can be fatal.
AIDS patients with disseminated histoplasmosis
vary in their response to amphotericin B, depending
on their general health and how well they tolerate the
side effects of the drug. Treatment often suppresses
the infection temporarily, but patients with AIDS are
always in danger of a relapse and must continue to
take medication for the rest of their lives to keep the
infection at bay. New combinations of therapies and
new drugs are constantly being evaluated, making
hard statistics on prognosis difficult to come by.
AIDS patients have problems with multiple opportunistic infections, making it difficult to isolate death
rates due to any one particular fungal infection.
1815

Histoplasmosis

The symptoms are usually mild and resemble those of
a cold or flu; fever, dry cough, enlarged lymph glands,
tiredness, and a general feeling of ill health. A small
number of people develop bronchopneumonia. About
95% of people who are infected either experience no
symptoms or have symptoms that clear up spontaneously. These people then have partial immunity to
re-infection.

Histoplasmosis

Histoplasmosis capsulatum
Histoplasma capsulatum. If a person inhales the spores of this fungus, they may contract histoplasmosis, an infectious disease
which can exist in three forms: acute or primary histoplasmosis, which causes flu-like symptoms; chronic histoplasmosis,
which affects the lungs and can be fatal; and disseminated histoplasmosis, which can affect multiple body systems and is often
fatal. (Illustration by Electronic Illustrators Group.)

KEY TERMS
Acidophilus—The bacteria Lactobacillus acidophilus, usually found in yogurt.
Adrenal gland—A pair of organs located above the
kidneys. The outer tissue of the gland produces the
hormones epinephrine (adrenaline) and norepinephrine, while the inner tissue produces several
steroid hormones.
Antigen—A foreign protein to which the body
reacts by making antibodies.
Bifidobacteria—A group of bacteria normally present in the intestine. Commercial supplements are
available.
Corticosteroids—A group of hormones produced
naturally by the adrenal gland or manufactured
synthetically. They are often used to treat inflammation. Examples include cortisone and prednisone.

1816

Prevention
Since the spores of H. capsulatum are so widespread, it is almost impossible to prevent exposure in
endemic areas. Dust suppression measures when
working with contaminated soil may help limit exposure. Individuals who are at risk of developing the
more severe forms of the disease should avoid situations where they will be exposed to bat and bird
droppings.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://www.lungusa.org>.
Histoplasmosis: Protecting Workers at Risk. Centers for
Disease Control and Prevention. <http://
www.cdc.gov/niosh/97146eng.html>.
National Center for Infectious Diseases. Atlanta, Georgia.
(404) 639-3158. <http://www.cdc.gov/ncidod/ncid/
ncid.htm>.
GALE ENCYCLOPEDIA OF MEDICINE

Hives

National Institute for Occupational Safety and Health.
Cincinnati, Ohio. (800) 356-4674.
OTHER

Histoplasmosis: Protecting Workers at Risk. Centers for
Disease Control and Prevention.
<http://www.cdc.gov/niosh/97146eng.html>.

Tish Davidson, A.M.

HIV infection see AIDS

Hives
Definition
Hives is an allergic skin reaction causing localized
redness, swelling, and itching.

Description
Hives is a reaction of the body’s immune system
that causes areas of the skin to swell, itch, and become
reddened (wheals). When the reaction is limited to
small areas of the skin, it is called ‘‘urticaria.’’
Involvement of larger areas, such as whole sections
of a limb, is called ‘‘angioedema.’’

Causes and symptoms
Causes
Hives is an allergic reaction. The body’s immune
system is normally responsible for protection from
foreign invaders. When it becomes sensitized to normally harmless substances, the resulting reaction is
called an allergy. An attack of hives is set off when
such a substance, called an allergen, is ingested,
inhaled, or otherwise contacted. It interacts with
immune cells called mast cells, which reside in the
skin, airways, and digestive system. When mast cells
encounter an allergen, they release histamine and
other chemicals, both locally and into the bloodstream. These chemicals cause blood vessels to become
more porous, allowing fluid to accumulate in tissue
and leading to the swollen and reddish appearance of
hives. Some of the chemicals released sensitize pain
nerve endings, causing the affected area to become
itchy and sensitive.
A wide variety of substances may cause hives in
sensitive people, including foods, drugs, and insect
bites or stings. Common culprits include:
GALE ENCYCLOPEDIA OF MEDICINE

Hives on the back of a young woman’s legs. The accompanying inflammation develops as an allergic reaction which
ranges in size from small spots to patches measuring several
inches across. (Photograph by John Radcliffe, Custom Medical
Stock Photo. Reproduced by permission.)



nuts, especially peanuts, walnuts, and Brazil nuts



fish, mollusks, and shellfish



eggs



wheat



milk



strawberries



food additives and preservatives



penicillin or other antibiotics



flu vaccines



tetanus toxoid vaccine



gamma globulin



bee, wasp, and hornet stings



bites of mosquitoes, fleas, and scabies
Symptoms

Urticaria is characterized by redness, swelling,
and itching of small areas of the skin. These patches
usually grow and recede in less than a day, but may
be replaced by hives in other locations. Angioedema
is characterized by more diffuse swelling. Swelling
of the airways may cause wheezing and respiratory
distress. In severe cases, airway obstruction may
occur.
1817

Hodgkin’s disease

Resources

KEY TERMS
Allergen—A substance capable of producing an
immediate type of hypersensitivity,or allergy.
Wheal—A smooth, slightly elevated area on the
body surface, which is redder or paler than the
surrounding skin.

PERIODICALS

Kirn, F. Timothy. ‘‘Desloratadine Improves Urticaria in
Clinical Setting.’’ Skin & Allergy News September
2004: 41.

Richard Robinson
Teresa G. Odle

HLA-B27 antigen test see Tissue typing
Diagnosis
Hives are easily diagnosed by visual inspection.
The cause of hives is usually apparent, but may require
a careful medical history in some cases.

HLA test see Human leukocyte antigen test
HMG-CoA reductase inhibitors see
Cholesterol-reducing drugs

Treatment
Mild cases of hives are treated with antihistamines,
such as diphenhydramine (Benadryl) or desloratadine
(Clarinex). Clarinex is non-sedating, meaning it will
not make patients drowsy. More severe cases may
require oral corticosteroids, such as prednisone.
Topical corticosteroids are not effective. Airway swelling may require emergency injection of epinephrine
(adrenaline).

Alternative treatment
An alternative practitioner will try to determine
what allergic substance is causing the reaction and
help the patient eliminate or minimize its effects. To
deal with the symptoms of hives, an oatmeal bath may
help to relieve itching. Chickweed (Stellaria media),
applied as a poultice (crushed or chopped herbs
applied directly to the skin) or added to bath water,
may also help relieve itching. Several homeopathic
remedies, including Urtica urens and Apis (Apis mellifica), may help relieve the itch, redness, or swelling
associated with hives.

Prognosis
Most cases of hives clear up within one to seven
days without treatment, providing the cause (allergen)
is found and avoided.

Prevention
Preventing hives depends on avoiding the allergen
causing them. Analysis of new items in the diet or
new drugs taken may reveal the likely source of the
reaction. Chronic hives may be aggravated by stress,
caffeine, alcohol, or tobacco; avoiding these may
reduce the frequency of reactions.
1818

Hodgkin’s disease
Hodgkin’s disease is a rare lymphoma, a cancer of
the lymphatic system.
Hodgkin’s disease, or Hodgkin’s lymphoma, was
first described in 1832 by Thomas Hodgkin, a British
physician. Hodgkin clearly differentiated between this
disease and the much more common non-Hodgkin’s
lymphomas. Prior to 1970, few individuals survived
Hodgkin’s disease. Now, however, the majority of
individuals with this cancer can be cured.
The lymphatic system is part of the body’s
immune system, for fighting disease, and a part of
the blood-producing system. It includes the lymph
vessels and nodes, and the spleen, bone marrow,
and thymus. The narrow lymphatic vessels carry
lymphatic fluid from throughout the body. The
lymph nodes are small organs that filter the lymphatic fluid and trap foreign substances, including
viruses, bacteria, and cancer cells. The spleen, in the
upper left abdomen, removes old cells and debris
from the blood. The bone marrow, the tissue
inside the bones, produces new red and white blood
cells.
Lymphocytes are white blood cells that recognize
and destroy disease-causing organisms. Lymphocytes
are produced in the lymph nodes, spleen, and bone
marrow. They circulate throughout the body in the
blood and lymphatic fluid. Clusters of immune cells
also exist in major organs.
Hodgkin’s disease is a type of lymphoma in which
antibody-producing cells of the lymphatic system
begin to grow abnormally. It usually begins in a
lymph node and progresses slowly, in a fairly
GALE ENCYCLOPEDIA OF MEDICINE

Dorothy Reed Mendenhall, the last of three children,
was born September 22, 1874, in Columbus, Ohio, to
William Pratt Reed, a shoe manufacturer, and Grace
Kimball Reed, both of whom had descended from English
settlers who came to America in the seventeenth century.
Mendenhall attended Smith College and obtained a
baccalaureate degree. Although she initially contemplated
a career in journalism, Mendenhall’s interest in medicine
was inspired by a biology course she attended.
Dorothy Reed Mendenhall was a well-respected
researcher, obstetrician, and pioneer in methods of childbirth. She was the first to discover that Hodgkin’s disease
was not a form of tuberculosis, as had been thought. This
finding received international acclaim. As a result of her
work, the cell type characteristic of Hodgkin’s disease
bears her name. The loss of her first child due to poor
obstetrics changed her research career to a lifelong effort
to reduce infant mortality rates. Mendenhall’s efforts paid
off with standards being set for weight and height for
children ages birth to six and also in programs that
stressed the health of both the mother and child in the
birthing process.

under the age of 10. The disease is very rare in children
under five.
The cause of Hodgkin’s disease is not known. It is
suspected that some interaction between an individual’s genetic makeup, environmental exposures, and
infectious agents may be responsible. Immune system
deficiencies also may be involved.
Early symptoms of Hodgkin’s disease may be
similar to those of the flu:


fevers, night sweats, chills



fatigue



loss of appetite



weight loss



itching



pain after drinking alcoholic beverages



swelling of one or more lymph nodes

Sudden or emergency symptoms of Hodgkin’s
disease include:


sudden high fever



loss of bladder and/or bowel control



numbness in the arms and legs and a loss of strength

As lymph nodes swell, they may push on other
structures, causing a variety of symptoms:
predictable way, spreading via the lymphatic vessels
from one group of lymph nodes to the next.
Sometimes it invades organs that are adjacent to the
lymph nodes. If the cancer cells spread to the blood,
the disease can reach almost any site in the body.
Advanced cases of Hodgkin’s disease may involve
the spleen, liver, bone marrow, and lungs.
There are different subtypes of Hodgkin’s disease:



pain due to pressure on nerve roots



loss of function in muscle groups served by compressed nerves



coughing or shortness of breath due to compression
of the windpipe and/or airways, by swollen lymph
nodes in the chest



kidney failure from compression of the ureters, the
tubes that carry urine from the kidneys to the bladder



swelling in the face, neck, or legs, due to pressure on
veins
paralysis in the legs due to pressure on the spinal cord



nodular sclerosis (30–60% of cases)



mixed cellularity (20–40% of cases)



lymphocyte predominant (5–10% of cases)



lymphocyte depleted (less than 5% of cases)





unclassified

As Hodgkin’s disease progresses, the immune
system becomes less effective at fighting infection.
Thus, patients with Hodgkin’s lymphoma become
more susceptible to both common infections caused
by bacteria and unusual (opportunistic) infections.
Later symptoms of Hodgkin’s disease include the
formation of tumors.

The American Cancer Society estimates that there
will be 7,400 new cases of Hodgkin’s disease in the
United States in 2001—3,500 in females and 3,900 in
males. It is estimated that 700 men and 600 women in
the United States will die of the disease in 2001.
Hodgkin’s disease can occur at any age. However,
the majority of cases develop in early adulthood
(ages 15–40) and late adulthood (after age 55).
Approximately 10–15% of cases are in children
under age 17. It is more common in boys than in girls
GALE ENCYCLOPEDIA OF MEDICINE

Significantly, as many as 75% of individuals with
Hodgkin’s disease do not have any typical symptoms.
As with many forms of cancer, diagnosis of
Hodgkin’s disease has two major components.
1819

Hodgkin’s disease

DOROTHY MENDENHALL
(1874–1964)

Hodgkin’s disease



identification of Hodgkin’s lymphoma as the cause
of the patient’s disease



staging of the disease to determine how far the cancer
has spread

The initial diagnosis of Hodgkin’s disease often
results from abnormalities in a chest x ray that was
performed because of nonspecific symptoms. The
physician then takes a medical history to check for
the presence of symptoms and conducts a complete
physical examination.
The size, tenderness, firmness, and location of
swollen lymph nodes are determined and correlated
with any signs of infection. In particular, lymph nodes
that do not shrink after treatment with antibiotics may
be a cause for concern. The lymph nodes that are most
often affected by Hodgkin’s disease include those of
the neck, above the collarbone, under the arms, and in
the chest above the diaphragm.
Diagnosis of Hodgkin’s disease requires either
the removal of an entire enlarged lymph node (an
excisional biopsy) or an incisional biopsy, in which
only a small part of a large tumor is removed. If the
node is near the skin, the biopsy is performed with a
local anesthetic. However, if it is inside the chest or
abdomen, general anesthesia is required.
The sample of biopsied tissue is examined under a
microscope. Giant cells called Reed-Sternberg cells
must be present to confirm a diagnosis of Hodgkin’s
disease. These cells, which usually contain two or more
nuclei, are named for the two pathologists who
discovered them. Normal cells have only one nucleus
(the organelle within the cell that contains the genetic
material). Affected lymph nodes may contain only a
few Reed-Sternberg cells and they may be difficult to
recognize. Characteristics of other types of cells in the
biopsied tissue help to diagnose the subtype of
Hodgkin’s disease.
A fine needle aspiration (FNA) biopsy, in which a
thin needle and syringe are used to remove a small
amount of fluid and bits of tissue from a tumor, has
the advantage of not requiring surgery. An FNA may be
performed prior to an excisional or incisional biopsy, to
check for infection or for the spread of cancer from
another organ. However an FNA biopsy does not
provide enough tissue to diagnose Hodgkin’s disease.
Occasionally, additional biopsies are required to
diagnose Hodgkin’s disease. In rare instances, other
tests, that detect certain substances on the surfaces of
cancer cells or changes in the DNA of cells, are used to
distinguish Hodgkin’s disease from non-Hodgkin’s
lymphoma.
1820

A scanning electron micrograph (SEM) image of dividing
Hodgkin’s cells from the pleural effusions (abnormal accumulations of fluid in the lungs) of a 55-year-old male patient.
(Photograph by Dr. Andrejs Liepins, Photo Researchers,
Inc. Reproduced by permission.)

Staging is very important in Hodgkin’s disease.
This is because the cancer usually spreads in a predictable pattern, without skipping sets of lymph nodes
until late in the progression of the disease.
Imaging of the abdomen, chest, and pelvis is used
to identify areas of enlarged lymph nodes and
abnormalities in the spleen or other organs.
Computerized axial tomography (CT or CAT) scans
use a rotating x-ray beam to obtain pictures. Magnetic
resonance imaging (MRI) uses magnetic fields and
radio waves to produce images of the body. Chest
x rays also may be taken. These images will reveal
rounded lumps called nodules in the affected lymph
nodes and other organs.
Another imaging technique for Hodgkin’s disease
is a gallium scan, in which the radioactive element
gallium is injected into a vein. The cancer cells take
up the gallium and a special camera that detects the
gallium is used to determine the location and size of
tumors. Gallium scans are used when Hodgkin’s
disease is in the chest and may be hard to detect by
other methods. Gallium scans also are used to monitor
progress during treatment.
A lymphangiogram, a radiograph of the lymphatic vessels, involves injecting a dye into a lymphatic
vessel in the foot. Tracking of the dye locates the
GALE ENCYCLOPEDIA OF MEDICINE



Stage III: The disease is in lymph node areas on both
sides of the diaphragm

Positron emission tomography (PET) scans are an
extremely accurate method for staging Hodgkin’s
disease. A very low dose of radioactive glucose, a
sugar, is injected into the body. The glucose travels
to metabolically active sites, including cancerous
regions that require large amounts of glucose. The
PET scan detects the radioactivity and produces
images of the entire body that distinguish between
cancerous and non-cancerous tissues.



Stage IIIE/IIISE: The disease extends into adjacent
areas or organs (IIIE) and/or the spleen (IIISE)



Stage IV: The disease has spread from the lymphatic
system to one or more other organs, such as the bone
marrow or liver

Anemia (a low red-blood-cell count), fevers, or
night sweats are indications that Hodgkin’s disease
may be in the bone marrow. In these cases, a bonemarrow biopsy, in which a large needle is used to
remove a narrow, cylindrical piece of bone, may be
necessary to determine the spread of the cancer.
Alternatively, an aspiration, in which a needle is used
to remove small bits of bone marrow, may be used.
The marrow usually is removed from the back of the
hip or other large bone.
Sometimes further staging, called pathological
staging or a staging laparotomy, is used for
Hodgkin’s disease. In this operation, a surgeon checks
the abdominal lymph nodes and other organs for cancer and removes small pieces of tissue. A pathologist
examines the tissue samples for Hodgkin’s disease
cells. Usually the spleen is removed (a splenectomy)
during the laparotomy. The splenectomy helps with
staging Hodgkin’s disease, as well as removing a
disease site.
All of the available treatments for Hodgkin’s disease have serious side effects, both short and longterm. However, with accurate staging, physicians and
patients often can choose the minimum treatment that
will cure the disease. The staging system for Hodgkin’s
disease is the Ann Arbor Staging Classification, also
called the Cotswold System or the Revised Ann Arbor
System.
Hodgkin’s disease is divided into four stages, with
additional substages:


Stage I: The disease is confined to one lymph node
area



Stage IE: The disease extends from the one lymph
node area to adjacent regions



Stage II: The disease is in two or more lymph node
areas on one side of the diaphragm (the muscle below
the lungs)



Stage IIE: The disease extends to adjacent regions of
at least one of these nodes

GALE ENCYCLOPEDIA OF MEDICINE

Treatment for Hodgkin’s disease depends both on
the stage of the disease and whether or not symptoms
are present. Stages are labeled with an A if no symptoms are present. If symptoms are present, the stage is
labeled with a B. These symptoms include:


loss of more than 10% of body weight over the previous six months



fevers above 100 (37.70 C) degrees F



drenching night sweats

Radiation therapy and/or chemotherapy (drug
therapy) are the standard treatments for Hodgkin’s
disease. If the disease is confined to one area of the
body, radiotherapy is usually used. This treatment,
with x rays or other high-energy rays, also is used
when the disease is in bulky areas such as the chest,
where chemotherapeutic drugs cannot reach all of the
cancer. External-beam radiation, a focused beam from
an external machine, is used to irradiate only the
affected lymph nodes. This procedure is called
involved field radiation.
More advanced stages of Hodgkin’s disease may
be treated with mantle field radiation, in which the
lymph nodes of the neck, chest, and underarms are
irradiated. Inverted Y field radiation is used to irradiate the spleen and the lymph nodes in the upper
abdomen and pelvis. Total nodal irradiation includes
both mantle field and inverted Y field radiation.
Since external-beam radiation damages healthy
tissue near the cancer cells, the temporary side effects
of radiotherapy can include sunburn-like skin
damage, fatigue, nausea, and diarrhea. Other temporary side effects may include a sore throat and difficulty
swallowing. Long-term side effects depend on the dose
and the location of the radiation and the age of the
patient. Since radiation of the ovaries causes permanent sterility (the inability to have offspring), the ovaries of girls and young women are protected during
radiotherapy. Sometimes the ovaries are surgically
moved from the region to be irradiated.
If the Hodgkin’s disease has progressed to additional lymph nodes or other organs, or if there is a
recurrence of the disease within two years of radiation
treatment, chemotherapy is used.
1821

Hodgkin’s disease

disease in the abdomen and pelvis. This method is used
less frequently and is usually not used with children.

Hodgkin’s disease

Chemotherapy utilizes a combination of drugs,
each of which kills cancer cells in a different way.
The most common chemotherapy regimens for
Hodgkin’s disease are MOPP (either mechlorethamine
or methotrexate with Oncovin, procarbazine, prednisone) and ABVD (Adriamycin or doxorubicin, bleomycin, vincristine, dacarbazine). Each of these
consists of four different drugs. ABVD is used more
frequently than MOPP because it has fewer severe side
effects. However MOPP is used for individuals who
are at risk for heart failure. The chemotherapeutic
drugs may be injected into a vein or muscle, or taken
orally, as a pill or liquid.
Children who are sexually mature when they
develop Hodgkin’s disease, and whose muscle and
bone mass are almost completely developed, usually
receive the same treatment as adults. Younger children
usually are treated with chemotherapy, since radiation
will adversely affect bone and muscle growth.
However, radiation may be used in low dosages, in
combination with chemotherapy. The chemotherapy
for children with Hodgkin’s disease usually includes
more drugs than ABVD and MOPP.
The side effects of chemotherapy for Hodgkin’s
disease depend on the dose of drugs and the length of
time they are taken. Since these drugs target rapidly
dividing cancer cells, they also affect normal cells that
grow rapidly. These include the cells of the bone
marrow, the linings of the mouth and intestines, and
hair follicles. Damage to bone marrow leads to lower
white blood cell counts and lower resistance to infection. It also leads to lower red blood cell counts, which
can result in fatigue and easy bleeding and bruising.
Damage to intestinal cells leads to a loss of appetite,
nausea, and vomiting. Mouth sores and hair loss also
are common side effects of chemotherapy. These side
effects disappear when the chemotherapy is discontinued. Some drugs can reduce or prevent the nausea and
vomiting.
Chemotherapy for Hodgkin’s disease may lead to
long-term complications. The drugs may damage the
heart, lungs, kidneys, and liver. In children, growth
may be impeded. Some chemotherapy can cause
sterility, so men may choose to have their sperm frozen
prior to treatment. Women may stop ovulating and
menstruating during chemotherapy. This may or may
not be permanent.
Treatment for higher-stage Hodgkin’s disease
often involves a combination of radiotherapy and
chemotherapy. Following three or four chemotherapy
regimens, involved field radiation may be directed at
the most affected areas of the body. The long-term side
1822

effects often are more severe when radiation and
chemotherapy are used in combination.
The development of a second type of cancer is the
most serious risk from radiation and chemotherapy
treatment for Hodgkin’s disease. In particular, there is
a risk of developing leukemia, breast cancer, bone
cancer, or thyroid cancer. Chemotherapy, particularly
MOPP, or chemotherapy in conjunction with radiotherapy, significantly increases the risk for leukemia.
Following treatment, the original diagnostic tests
for Hodgkin’s disease are repeated, to determine
whether all traces of the cancer have been eliminated
and to check for long-term side effects of treatment. In
resistant Hodgkin’s disease, some cancer cells remain
following treatment. If the cancer continues to spread
during treatment, it is called progressive Hodgkin’s disease. If the disease returns after treatment, it is known as
recurrent Hodgkin’s disease. It may recur in the area
where it first started or elsewhere in the body. It may
recur immediately after treatment or many years later.
Additional treatment is necessary with these types
of Hodgkin’s disease. If the initial treatment was
radiation therapy alone, chemotherapy may be used,
or vice versa. Chemotherapy with different drugs, or
higher doses, may be used to treat recurrent
Hodgkin’s. However, radiation to the same area is
never repeated.
An autologous bone marrow and/or a peripheral
blood stem cell transplantation (PBSCT) often is
recommended for treating resistant or recurrent
Hodgkin’s disease, particularly if the disease recurs
within a few months of a chemotherapy-induced
remission. These transplants are autologous because
they utilize the individual’s own cells. The patient’s
bone marrow cells or peripheral blood stem cells
(immature bone marrow cells found in the blood) are
collected and frozen prior to high-dosage chemotherapy, which destroys bone marrow cells. A procedure
called leukapheresis is used to collect the stem cells.
Following the high-dosage chemotherapy, and possibly radiation, the bone marrow cells or stem cells are
reinjected into the individual.
Most complementary therapies for Hodgkin’s disease are designed to stimulate the immune system to
destroy cancer cells and repair normal cells that have
been damaged by treatment. These therapies are used
in conjunction with standard treatment.
Immunologic therapies, also known as immunotherapies, biological therapies, or biological response
modifier therapies, utilize substances that are produced
by the immune system. These include interferon (an
immune system protein), monoclonal antibodies
GALE ENCYCLOPEDIA OF MEDICINE

Antibody—An immune system protein that recognizes a specific foreign molecule.
Biopsy—The removal of a small sample of tissue for
examination under a microscope; used for the diagnosis of cancer and to check for infection.
Bone marrow—Tissue inside the bones that produce
red and white blood cells.
Chemotherapy—Treatment with various combinations of chemicals or drugs, particularly for the treatment of cancer.
Epstein-Barr virus (EBV)—Very common virus that
infects immune cells and can cause mononucleosis.
Interferon—A potent immune-defense protein produced by viral-infected cells; used as an anti-cancer
and anti-viral drug.
Interleukins—A family of potent immune-defense
molecules; used in various medical therapies.

thymus, that produce and carry white blood cells to
fight disease.
Lymphocyte—White blood cells that produce antibodies and other agents for fighting disease.
PBSCT—Peripheral blood stem cell transplant; a
method for replacing blood-forming cells that are
destroyed by cancer treatment.
Radiotherapy—Disease treatment involving exposure to x rays or other types of radiation.
Reed-Sternberg cells—An abnormal lymphocyte
that is characteristic of Hodgkin’s disease.
Spleen—An organ of the lymphatic system, on the
left side of the abdomen near the stomach; it produces and stores lymphocytes, filters the blood, and
destroys old blood cells.
Splenectomy—Surgical removal of the spleen.

Laparotomy—A surgical incision of the abdomen.
Leukapheresis—A technique that uses a machine to
remove stem cells from the blood; the cells are frozen and then returned to the patient following treatment that has destroyed the bone marrow.

Staging—The use of various diagnostic methods to
accurately determine the extent of disease; used to
select the appropriate type and amount of treatment
and to predict the outcome of treatment.
Stem cells—The cells from which all blood cells are
derived.

Lymph nodes—Small round glands, located throughout the body and containing lymphocytes that remove
foreign organisms and debris from the lymphatic fluid.

Thymus—An organ of the lymphatic system, located
behind the breast bone, that produces the T lymphocytes of the immune system.

Lymphatic system—The vessels, lymph nodes, and
organs, including the bone marrow, spleen, and

Thyroid—A gland in the throat that produces
hormones that regulate growth and metabolism.

(specially engineered antibodies), colony-stimulating
(growth) factors (such as filgrastim), and vaccines.
Many immunotherapies for Hodgkin’s disease are
experimental and available only through clinical trials.
These biological agents may have side effects.

The one-year relative survival rate following
treatment for Hodgkin’s disease is 93%. Relative survival rates do not include individuals who die of causes
other than Hodgkin’s disease. The percentage of
individuals who have not died of Hodgkin’s disease
within five years of diagnosis is 90–95% for those
with stage I or stage II disease. The figure is 85–90%
for those diagnosed with stage III Hodgkin’s and
approximately 80% for those diagnosed with stage
IV disease. The 15-year relative survival rate is 63%.
Approximately 75% of children are alive and cancer
free 20 years after the original diagnosis of Hodgkin’s.

Coenzyme Q10 (CoQ10) and polysaccharide K
(PSK) are being evaluated for their ability to stimulate
the immune system and protect healthy tissue, as well as
possible anti-cancer activities. Camphor, also known as
714-X, green tea, and hoxsey (which is a mixture of a
number of substances), have been promoted as immune
system enhancers. However there is no evidence that
they are effective against Hodgkin’s disease. Hoxsey, in
particular, can produce serious side effects.
Hodgkin’s disease, particularly in children, is one
of the most curable forms of cancer. Approximately
90% of individuals are cured of the disease with
chemotherapy and/or radiation.
GALE ENCYCLOPEDIA OF MEDICINE

Acute myelocytic leukemia, a very serious cancer,
may develop in as many as 2–6% of individuals receiving certain types of treatment for Hodgkin’s disease.
Women under the age of 30 who are treated with
radiation to the chest have a much higher risk for
developing breast cancer. Both men and women are
1823

Hodgkin’s disease

KEY TERMS

Holistic medicine

at higher risk for developing lung or thyroid cancers as
a result of chest irradiation.
Individuals with the type of Hodgkin’s disease
known as nodular lymphocytic predominance have a
2% chance of developing non-Hodgkin’s lymphoma.
Apparently, this is a result of the Hodgkin’s disease
itself and not the treatment.
Rosalyn Carson-DeWitt, MD
Margaret Alic, Ph.D.

Holistic medicine
Definition
Holistic medicine is a term used to describe therapies that attempt to treat the patient as a whole person.
That is, instead of treating an illness, as in orthodox
allopathy, holistic medicine looks at an individual’s
overall physical, mental, spiritual, and emotional wellbeing before recommending treatment. A practitioner
with a holistic approach treats the symptoms of illness
as well as looking for the underlying cause of the
illness. Holistic medicine also attempts to prevent illness by placing a greater emphasis on optimizing
health. The body’s systems are seen as interdependent
parts of the person’s whole being. Its natural state is
one of health, and an illness or disease is an imbalance in
the body’s systems. Holistic therapies tend to emphasize
proper nutrition and avoidance of substances—such as
chemicals—that pollute the body. Their techniques are
non-invasive.
Some of the world’s health systems that are holistic in nature include naturopathic medicine, homeopathy, and traditional Chinese medicine. Many
alternative or natural therapies have a holistic
approach, although that is not always the case. The
term complementary medicine is used to refer to the
use of both allopathic and holistic treatments. It is
more often used in Great Britain, but is gaining acceptance in the United States.
There are no limits to the range of diseases and
disorders that can be treated in a holistic way, as the
principle of holistic healing is to balance the body,
mind, spirit, and emotions so that the person’s whole
being functions smoothly. When an individual seeks
holistic treatment for a particular illness or condition,
other health problems improve without direct treatment, due to improvement in the performance of the
immune system, which is one of the goals of holistic
medicine.
1824

Origins
The concept of holistic medicine is not new. In the
4th century B.C., Socrates warned that treating one part
of the body only would not have good results.
Hippocrates considered that many factors contribute
to the health or otherwise of a human being, weather,
nutrition, emotional factors, and in our time, a host of
different sources of pollution can interfere with health.
And of course, holistic medicine existed even before
ancient Greece in some ancient healing traditions, such
as those from India and China, which date back over
5,000 years. However, the term ‘‘holistic’’ only became
part of everyday language in the 1970s, when Westerners
began seeking an alternative to allopathic medicine.
Interestingly, it was only at the beginning of the
twentieth century that the principles of holistic medicine fell out of favor in Western societies, with the
advent of major advances in what we now call allopathic medicine. Paradoxically, many discoveries of
the twentieth century have only served to confirm
many natural medicine theories. In many cases,
researchers have set out to debunk holistic medicine,
only to find that their research confirms it, as has been
the case, for example, with many herbal remedies.

Purpose
Many people are now turning to holistic medicine,
often when suffering from chronic ailments that have
not been successfully treated by allopathic means.
Although many wonderful advances and discoveries
have been made in modern medicine, surgery and
drugs alone have a very poor record for producing
optimal health because they are designed to attack
illness. Holistic medicine is particularly helpful in
treating chronic illnesses and maintaining health
through proper nutrition and stress management.

Description
There are a number of therapies that come under
the umbrella of ‘‘holistic medicine.’’ They all use basically the same principles, promoting not only physical
health, but also mental, emotional, and spiritual
health. Most emphasize quality nutrition. Refined
foods typically eaten in modern America contain
chemical additives and preservatives, are high in fat,
cholesterol, and sugars, and promote disease.
Alternative nutritionists counter that by recommending whole foods whenever possible and minimizing
the amount of meat—especially red meat—that is
consumed. Many alternative therapies promote vegetarianism as a method of detoxification.
GALE ENCYCLOPEDIA OF MEDICINE

a runaway best-seller. Perhaps the best-known proponent
of naturalistic healing methods, Weil has been trying to
establish a field he calls integrative medicine. He is director of Tucson’s Center for Integrative Medicine, which he
founded in 1993. In 1997, he began training doctors in the
discipline at the University of Arizona, where he teaches.

(Photograph by M. Greenberg. Gamma Liaison. Reproduced by
permission.)

After getting his bachelor’s degree in botany from
Harvard University, Weil applied for admission to
Harvard Medical School in 1964. During his second
year, he led a group of students who argued they could
succeed better studying on their own than going to classes;
in fact, the group got higher scores on their final exams
than their classmates. After graduating from Harvard
Medical School, he volunteered at the notorious countercultural Haight-Asbury Free Clinic in San Francisco, CA.
Later in 1969, Weil got a job in Washington, DC, with the
National Institute of Mental Health’s Drug Studies
Division. From 1971 to 1975, he traveled extensively in
South America and Africa, soaking up information about
medicinal plants, shamanism, and natural healing techniques. He never returned to the practice of conventional
medicine.

Dr. Andrew Weil, a Harvard-educated physician,
adds credibility and expertise to the natural healing methods he espouses in his best-selling books, on his Internet
Web site, in his talk show appearances, and in his popular
audio CD of music and meditation. Weil’s Spontaneous
Healing spent more than a year on the best-seller list, and
his 1997 book, Eight Weeks to Optimum Health, also was

His approach to alternative medicine is eclectic, mingling traditional medicine with herbal therapy, acupuncture, homeopathy, chiropractic, hypnotism, cranial
manipulation, and other alternative healing methods.
Though his books discuss the benefits of everything from
healing touch to herbal cures, Weil doesn’t dismiss the
benefits of standard Western medicine when appropriate.

The aim of holistic medicine is to bring all areas of
an individual’s life, and most particularly the energy
flowing through the body, back into harmony.
Ultimately, of course, only the patient can be responsible for this, for no practitioner can make the necessary adjustments to diet and lifestyle to achieve health.
The practice of holistic medicine does not rule out the
practice of allopathic medicine; the two can complement each other.

Here are some of the major holistic therapies:

A properly balanced holistic health regimen, which
takes into consideration all aspects of human health
and includes noninvasive and nonpharmaceutical healing methods, can often completely eradicate even acute
health conditions safely. If a patient is being treated
with allopathic medicine, holistic therapies may at least
support the body during treatment, and alleviate the
symptoms that often come with drug treatments and
surgery. In addition, holistic therapies aim at the underlying source of the illness, to prevent recurrence.
GALE ENCYCLOPEDIA OF MEDICINE



herbal medicine



homeopathy



naturopathic medicine



traditional Chinese medicine



Ayurvedic medicine



nutritional therapies



chiropractic



stress reduction



psychotherapy



massage

Because holistic medicine aims to treat the whole
person, holistic practitioners sometimes may advise
treatment from more than one type of practitioner.
This is to ensure that all aspects of health are
1825

Holistic medicine

A N D R E W W E I L (1942– )

Holistic medicine

addressed. Some practitioners also specialize in more
than one therapy, and so may be able to offer more
comprehensive assistance.

Preparations
How to choose a holistic practitioner


How did you hear of this therapist? A personal
referral can sometimes be more reliable than a
professional one. What do other professionals say
about this therapist? What qualifications, board certification, or affiliations does this practitioner have?



How do you feel personally about this practitioner?
Do you feel comfortable in his/her office and with
his/her staff? Is your sense of well being increased?
Are you kept waiting for appointments?



Do you have confidence in this practitioner, does he/
she respect you as a person? Does he/she show an
interest in your family, lifestyle, and diet? Are
various treatment options explained to you?



Is your personal dignity respected?



Do you feel that this practitioner is sensitive to your
feelings and fears regarding treatment?



Is this practitioner a good advertisement for his/her
profession? Signs of stress or ill health may mean
that you would be better off choosing another
practitioner.



Do you feel that you are rushed into decisions, or do
you feel that you are allowed time to make an
informed choice regarding treatment?



Are future health goals outlined for you? And do you
feel that the practitioner is taking your progress
seriously?



Do you feel unconditionally accepted by this
practitioner?



Would you send your loved ones to this practitioner?

If you answered yes to all the above, then you have
found a suitable practitioner. The cost of treatment by a
holistic therapist varies widely, depending on the level
of qualification and the discipline, so it is best to discuss
how much treatment can be expected to cost with a
practitioner before beginning a course. Some forms of
holistic treatment may be covered by health insurance.

Precautions
Many people who try holistic therapies focus on
one area of their health only, often detoxification and
nutrition. However, practitioners stress that it is only
when all areas of a person’s potential well being are
1826

tackled that total health and happiness can be
achieved. They stress that the spiritual and emotional
health contribute just as much as physical and mental
health to a person’s overall state of well-being.
When seeking treatment from a holistic practitioner, it is important to ensure that they are properly
qualified. Credentials and reputation should always be
checked. In addition, it is important that allopathic
physicians and alternative physicians communicate
about a patient’s care.

Side effects
One of the main advantages of holistic therapies is
that they have few side effects when used correctly. If a
reputable practitioner is chosen, and guidelines are
adhered to, the worst that typically happens is that
when lifestyle is changed, and fresh nutrients are provided, the body begins to eliminate toxins that may
have accumulated in the cells over a lifetime.
Often this results in what is known in alternative
medicine circles as a ‘‘healing crisis.’’ This comes
about when the cells eliminate poisons into the
blood stream all at the same time, throwing the
system into a state of toxic overload until it can
clear the ‘‘backlog.’’ Symptoms such as nausea, headaches, or sensitivities to noise and other stimulations
may be experienced.
The answer to most otherwise healthy patients is
often just to lie quietly in a darkened room and take
herbal teas. However, in the case of someone who has
a serious illness, such as arthritis, colitis, diabetes, or
cancer, (the list is much longer than this), it is strongly
advised that they seek the help of a qualified practitioner. Therapists can help patients achieve detoxification in a way that causes the least stress to their
bodies.

Research and general acceptance
Traditionally, holistic medicine, in all its different
forms, has been regarded with mistrust and skepticism
on the part of the allopathic medical profession. This
situation is gradually changing. As of the year 2000,
many insurance companies will provide for some form
of alternative, or complementary treatment.
In addition, many allopathic physicians, recognizing the role alternative medicine can play in overall
health and well being, are actually referring patients to
reputable practitioners, particularly chiropractic and
relaxation therapists, for help with a varied range of
complaints.
GALE ENCYCLOPEDIA OF MEDICINE

Holistic or alternative medicine practitioners are
usually affiliated with an organization in their field.
Training varies tremendously with the category, and
ranges from no qualifications at all—experience
only—to holding a Ph.D. from an accredited university. Again, credentials and memberships should be
checked by prospective patients.
An excellent source for qualified practitioners is
the American Board of Holistic Medicine, (AHBM),
which was incorporated in 1996. Also, the American
Holistic Medicine Association has a comprehensive
list of practitioners in all types of therapies across the
United States, which they call ‘‘the holistic doctor
finder.’’ However, they stress that it is the responsibility of the patient to check each practitioner’s credentials prior to treatment.
The ABHM has established the core curriculum
upon which board certification for holistic medicine
will be based. It includes the following twelve categories:
Body
Physical and environmental health


nutritional medicine



exercise medicine



environmental medicine

KEY TERMS
Detoxification—Treating the body in such a way
that it eliminates poisons accumulated in the cells.
Healing crisis—When the body begins to eliminates toxins at an accelerated rate, unpleasant
sensations may be experienced.

and doctors of osteopathic medicine (DOs) from
every specialty, and to medical students studying for
those degrees. Associate membership is open to health
care practitioners who are certified, registered or
licensed in the state in which they practice. The mission of the AHMA is to support practitioners in their
personal and professional development as healers,
and to educate physicians about holistic medicine.
Resources
ORGANIZATIONS

American Holistic Medicine Association. 4101 Lake
Boone Trail, Suite 201, Raleigh, NC 27607.
<http://www.holisticmedicine.org/index.html>.
Holistic medicine Website. <http://www.holisticmed.com/
whatis.html>.

Patricia Skinner

Mind
Mental and emotional health


behavioral medicine
Spirit
Spiritual health



spiritual attunement



social health
The six specialized areas:



biomolecular diagnosis and therapy



botanical medicine



energy medicine



ethno-medicine—including traditional Chinese
medicine, Ayurveda, and Native American medicine



homeopathy



manual medicine

Founded in 1978 for the purpose of uniting practitioners of holistic medicine, membership of the
AHMA is open to licensed medical doctors (MDs)
GALE ENCYCLOPEDIA OF MEDICINE

Holter monitoring
Definition
Holter monitoring is continuous monitoring of the
electrical activity of a patient’s heart muscle (electrocardiography) for 24 hours, using a special portable device
called a Holter monitor. Patients wear the Holter
monitor while carrying out their usual daily activities.

Purpose
Holter monitoring is used to help determine
whether someone has an otherwise undetected heart
disease, such as abnormal heart rhythm (cardiac
arrhythmia), or inadequate blood flow through the
heart. Specifically, it can detect abnormal electrical
activity in the heart that may occur randomly or only
under certain circumstances, such as during sleep or
periods of physical activity or stress, which may or
may not be picked up by standard, short-term electrocardiography performed in a doctor’s office.
1827

Holter monitoring

Training and certification

Holter monitoring

Traditionally, an exercise stress test has been used
to screen people for ‘‘silent’’ heart disease (heart
disease with none of the usual symptoms). However,
an exercise stress test is not completely foolproof,
often producing false negative results (indicating no
heart disease when heart disease is actually present)
and false positives (indicating heart disease when
there is none). Furthermore, some people cannot
undergo exercise stress testing because of other
medical conditions, such as arthritis.
Holter monitoring, also known as ambulatory or
24-hour electrocardiography, offers an alternate
means of testing people for heart disease. By monitoring electrocardiographic activity throughout the day,
Holter monitoring can uncover heart problems that
occur during the patient’s everyday activities. It can
also help to recognize any activities that may be
causing the heart problems. And it can define and
correlate symptoms that may be caused by irregularities of the heart.

Precautions
Holter monitoring is an extremely safe procedure
and no special precautions are required.

Description
The technician affixes electrodes on the surface of
the skin at specific areas of the patient’s chest, using
adhesive patches with special gel that conducts electrical impulses. Typically, electrodes are placed under
each collarbone and each bottom rib, and several electrodes are placed across the chest in a rough outline of
the heart. The electrodes are attached to a portable
electrocardiographic device called a Holter monitor,
which records the electrical activity of the heart over
24–48 hours. The device is worn over the patient’s
shoulder or attached to a belt around the waist.
The Holter monitor records the continuous electrical activity throughout the course of the day, while
the patient carries out his or her daily activities.
During this time, the patient also keeps a detailed log
or diary, recording his or her various activities, such as
exercise, eating, sleeping, straining, breathing too hard
(hyperventilating), and any stressful situations. The
patient also notes the time and circumstances of any
symptoms–especially chest pain, dizziness, shortness of
breath, heart palpitations, and any other signs of heart
trouble. Some Holter monitors allow patients to
record their symptoms electronically, highlighting
the portion of the electrocardiogram recorded while
the symptoms are occurring.
1828

A male patient wears electrodes attached to his chest, which
is connected to a Holter monitor at his waist. (Photograph by
Dr. P. Marazzi, Photo Researchers, Inc. Reproduced by
permission.)

After 24–48 hours, the Holter monitor is removed.
A computer-assisted analysis is performed on the
electrocardiographic recording, and the doctor compares the recording against the patient’s log to see if
there is any correlation between electrocardiographic
abnormalities and any of the patient’s activities or
symptoms. The physician makes a final interpretation.

Preparation
In the doctor’s office, electrodes are attached to
the patient’s chest. In some cases, the patient’s chest
hair may have to be shaved to facilitate attaching the
electrodes. The patient then begins carrying the monitor on a shoulder harness, in a pocket, or on the belt
while carrying out his or her usual daily routine. The
patient should inform the doctor of any drugs he or
she may be taking, because certain drugs can alter
heart rhythms and may affect the results of the test.
GALE ENCYCLOPEDIA OF MEDICINE

Cardiac arrhythmia—An abnormal heart rhythm.
Electrocardiography—Recording of the electrical
activity of the heart muscle, used to diagnose
certain heart abnormalities.

Holtzman ink blot test
Definition
The Holtzman Inkblot Technique (HIT) is a projective personality assessment test for persons ages five
and up.

Purpose
Aftercare
The patient returns to the doctor’s office to have
the monitor and electrodes removed. No special measures need to be taken following Holter monitoring.
The test results are usually available within a few days
after the monitor is removed.

Risks
There are no known risks associated with Holter
monitoring. The main complaint that people have
with Holter monitoring is that the monitor may be
cumbersome and interfere with certain activities, especially sleeping. Bathing and showering are not allowed
during the study.

The HIT is used to assess the personality structure
of a test subject. It is sometimes used as a diagnostic
tool in assessing schizophrenia, depression, addiction,
and character disorders.

Precautions
Psychometric testing requires a clinically trained
examiner. The HIT should be administered and interpreted by a trained psychologist, psychiatrist, or
appropriately trained mental health professional.
Some consider projective tests to be less reliable
than objective personality tests. If the examiner is not
well-trained in psychometric evaluation, subjective
interpretations may affect the outcome of the test.

Description
Normal results
A normal Holter monitoring test shows relatively
normal electrical activity in the heart around the clock
and no evidence of silent ischemia (deprivation of
oxygen-rich blood).

Abnormal results
An abnormal result on Holter monitoring may
indicate ischemia to the heart muscle or heart rhythm
disturbances. Abnormalities are especially likely to
show up during periods of stress or heavy activity,
but sometimes serious abnormalities are recorded
while the patient is sleeping.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Robert Scott Dinsmoor
GALE ENCYCLOPEDIA OF MEDICINE

The HIT, developed by psychologist Wayne
Holtzman and colleagues, was introduced in 1961.
The test was designed to overcome some of the deficiencies of its famous predecessor, the Rorschach
Inkblot Test.
Unlike the Rorschach, the Holtzman is a standardized measurement with clearly defined objective
scoring criteria. The HIT consists of 45 inkblots. The
test administrator, or examiner, has a stack of 47
cards with inkblots (45 test cards and 2 practice
cards) face down in front of him or her. The examiner
hands each card to the subject and asks the test
subject what he or she sees in the inkblot. Only one
response per inkblot is requested. Occasionally, the
examiner may ask the test subject to clarify or elaborate on a response. The Administration of the HIT
typically takes 50–80 minutes. The HIT is then scored
against 22 personality-related characteristics.
The HIT can also be administered in a group
setting. In group testing, 30–45 inkblots are projected
onto a screen and test subjects provide written
responses to each inkblot.
The 1997 Medicare reimbursement rate for psychological and neuropsychological testing is $58.35 an
1829

Holtzman ink blot test

KEY TERMS

Homeopathic medicine

Purpose

KEY TERMS
Projective personality assessment—A test in which
the subject is asked to interpret ambiguous stimuli,
such as an inkblot. The subject’s responses provide
insight into his or her thought processes.
Standardization—The process of determining
established norms and procedures for a test to act
as a standard reference point for future test results.

hour. Billing time typically includes test administration, scoring and interpretation, and reporting. Many
insurance plans cover all or a portion of diagnostic
psychological testing.

Normal results
Because of the complexity of the scoring process
and the projective nature of the test, results for the
HIT should only be interpreted by a clinically trained
psychologist, psychiatrist, or appropriately trained
mental health professional.
Resources
ORGANIZATIONS

American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.

Paula Anne Ford-Martin

Homeopathic physicians seek to cure their
patients on the physical, mental and emotional levels,
and each treatment is tailored to a patient’s individual needs. Homeopathy is generally a safe treatment, as it uses medicines in extremely diluted
quantities, and there are usually minimal side effects.
Its non-toxicity makes it a good choice for the treatment of children. Another benefit of homeopathy is
the cost of treatments; homeopathic remedies are
inexpensive, often a fraction of the cost of conventional drugs.
Homeopathic treatment has been shown effective in treating many conditions. Colds and flu may
be effectively treated with aconite and bryonia.
Influenza suffers in a double-blind study found that
they were twice as likely to recover in 48 hours when
they took homeopathic remedies. Studies have been
published in British medical journals confirming the
efficacy of homeopathic treatment for rheumatoid
arthritis. Homeopathic remedies are effective in
treating infections, circulatory problems, respiratory
problems, heart disease, depression and nervous
disorders, migraine headaches, allergies, arthritis,
and diabetes. Homeopathy is a good treatment to
explore for acute and chronic illnesses, particularly
if these are found in the early stages and where
there is not severe damage. Homeopathy can be
used to assist the healing process after surgery or
chemotherapy.

Description
Origins

Homeopathic medicine
Definition
Homeopathy, or homeopathic medicine, is a holistic system of treatment that originated in the late
eighteenth century. The name homeopathy is derived
from two Greek words that mean ‘‘like disease.’’ The
system is based on the idea that substances that produce
symptoms of sickness in healthy people will have a
curative effect when given in very dilute quantities to
sick people who exhibit those same symptoms.
Homeopathic remedies are believed to stimulate the
body’s own healing processes. Homeopaths use
the term ‘‘allopathy,’’ or ‘‘different than disease,’’ to
describe the use of drugs used in conventional medicine
to oppose or counteract the symptom being treated.
1830

Homeopathy was founded by German physician
Samuel Hahnemann (1755–1843), who was much
disturbed by the medical system of his time, believing
that its cures were crude and some of its strong drugs
and treatments did more harm than good to patients.
Hahnemann performed experiments on himself using
Peruvian bark, which contains quinine, a malaria
remedy. He concluded that in a healthy person, quinine creates the same symptoms as malaria, including
fevers and chills, which is the reason why it is effective
as a remedy. He then began to analyze the remedies
available in nature by what he called provings.
Provings of homeopathic remedies are still compiled
by dosing healthy adults with various substances and
documenting the results, in terms of the dose needed
to produce the symptoms and the length of the dose’s
effectiveness. The provings are collected in large
homeopathic references called materia medica or
materials of medicine.
GALE ENCYCLOPEDIA OF MEDICINE

Hahnemann was born in Meissen, Saxony (now part
of Germany) into a financially challenged middle class
family. His parents initially educated him at home,
where his father taught him never to accept anything he
learned without first questioning it. He graduated as a
physician at Erlangen in 1779 after studying at Leipzig
and Vienna. He was also fluent in English, German,
Italian, French, Greek, Arabic, Latin and Hebrew.
At age 27 he married his first wife, Johanna Henriette
Kuchler, the daughter of an apothecary, with whom he
had 11 children.
Living in poverty, Hahnemann began practicing
medicine in 1781 and translating scientific texts to supplement his income. However, disillusioned with medicine,
he eventually gave it up entirely.

(Corbis Corporation. Reproduced by permission.)

Samuel Christian Hahnemann created and developed the system called homeopathy. It is also known as
similia similibus curentor or like cures like. Although
his new methods initially met with ridicule and criticism,
by the time of his death they were accepted the world
over as a result of the great success he had with his
new cure.

Hahnemann formulated these principles of
homeopathy:


Law of Similars (like cures like)



Law of the Infinitesimal Dose (The more diluted a
remedy is, the more potent it is.)



illness is specific to the individual

Hahnemann’s Law of Similars was based on
thinking that dated back to Hippocrates in the fourth
century B.C. It is the same thinking that provided the
basis for vaccinations created by Edward Jenner and
Louis Pasteur. These vaccines provoke a reaction in
the individual that protects against the actual disease.
Allergy treatments work the same way. By exposing a
person to minute quantities of the allergen, the person’s tolerance levels are elevated.
The Law of the Infinitesimal Dose has always
caused controversy among those outside the field of
homeopathy. Hahnemann contended that as he
GALE ENCYCLOPEDIA OF MEDICINE

He discovered the concept of homeopathy when
considering the effect of quinine on malaria, and went
on to cure soldiers and then sufferers of a typhus epidemic
with astounding success. He documented his discoveries
in the Organon, a treatise on his work. Homeopathy also
proved its worth in 1831 when there was an outbreak of
cholera. Hahnemann used homeopathic treatment with a
96% success rate, compared to the 41% of allopathic
medicine. He also wrote his Materia Medica Pura.
In 1834, Hahnemann met his second wife, Marie
Melanie d’Hervilly. Despite a great difference in age,
they were happily married until his death in Paris on July
2, 1843, at the age of 88.

diluted his remedies with water and alcohol and succussed, or shook, them, the remedies actually worked
more effectively. In fact, diluted homeopathic remedies may have no chemical trace of the original substance. Practitioners believe that the electromagnetic
energy of the original substance is retained in the
dilution, but toxic side effects of the remedy are not.
It is this electrochemical ‘‘message’’ that stimulates
the body to heal itself.
Homeopathic practitioners believe that illness is
specific to an individual. In other words, two people
with severe headaches may not receive the same remedies. The practitioner will ask the patient questions
about lifestyle, dietary habits, and personality traits,
as well as specific questions about the nature of the
headache and when it occurs. This information gathering is called profiling or case-taking.
In the early 1900s, homeopathy was popular in
America, with over 15 percent of all doctors being
homeopathic. There were 22 major homeopathic
1831

Homeopathic medicine

S A M U E L H A H N E M A N N (1755–1843)

Homeopathic medicine

Homeopathic Remedies That Work

Homeopathic Remedies That Work [Continued]

Name

Description

Name

Description

Aconite

Commonly known as monkshood, aconite is highly
toxic. A nontoxic, diluted extract of aconite is used in
homeopathy to treat symptoms similar to that of poison.
Commonly known as red onion, homeopathic physicians use a dilute extract of red onion to treat symptoms
similar to that of red onion—watery eyes, burning,etc.
Commonly known as the honeybee, apis as a homeopathic remedy is made from the body of the bee. It is
used to treat symptoms similar to that of a bee sting—
redness, swelling, etc.
Commonly known as the mountain daisy, arnica is used
by homeopathic physicians to treat bruises, sprains, and
strains.
Also known as ars alb, arsenicum album is a diluted
form of arsenic, a metallic poison. It is used by homeopathic physicians to treat symptoms similar to the
effects of arsenic poisoning—dehydration,
burning pain, etc.
Commonly known as deadly knightshade, belladonna is
used in homeopathy to treat symptoms of dry mouth,
nausea, delirium, etc.
Commonly known as wild hops, bryonia is used in
homeopathy to treat vomiting, diarrhea, inflammation,
etc.
Also known as calcium carbonate or calc carb, it is used
in homeopathy to treat symptoms of exhaustion,
depression, and anxiety.
Commonly known as Spanish fly, cantharis is used in
homeopathy to treat conditions with symptoms of
abdominal cramps, vomiting, diarrhea, convulsions, etc.
Derived from German chamomile, it is used in
homeopathy to treat irritability, impatience, etc. It is
most often prescribed to children.
Also known as ferrum phos or iron phosphate, it is
used to treat symptoms of low energy and anemia.
Also known as yellow jasmine, it is used to treat conditions that effect vision, balance, though, and
locomotion.
Derived from the inner layer of oyster shells, hepar
sulphuris is used to treat infection.
Commonly known as St. John’s wort, hypericum is used
to treated nerve damage.
Derived from seeds of a plant, this homeopathic remedy
is prescribed to treat conditions with symptoms such as
headache, cramping, and tremors.
Ipecac induces vomiting and causes gastrointestinal
distress. Homeopaths prescribe it to treat similar
symptoms.
Commonly known as potassium bichromate, kali
bichromicum is a poison used also in textile dyes, wood
stain, etc. Homeopaths use it to treat localized pain.
Derived from the venom of the bushmaster snake, this
homeopathic remedy is used to treat conditions that
cause the same symptoms as the venom itself.
Also known as marsh tea, ledum is used to treat infections, most often from animal bites, stings, cuts, etc.
Commonly known as club moss, lycopodium is used to
treat diarrhea, digestive upset, etc.
Also known as quicksilver, it is used to treat symptoms
of sweats, shaking, nausea, etc.
Commonly known as salt, it is used to treat conditions
that cause excessive thirst and salt cravings.
It is used to treat symptoms caused by overeating and
too much caffeine or alcohol.
It is used to treat symptoms of excessive thirst, fatigue,
and nervousness.

Pulsatilla

It is used to treat conditions that are accompanied
by discharge, such as bedwetting, sinusitis, etc.
Commonly known as poison ivy, homeopaths use it
to treat conditions with symptoms of fever, swollen
glands, and restlessness.
It is used to treat conditions with bruising, such as
tennis elbow, sciatica, etc.
Sepia is the discharge used by the cuttlefish to
disappear from a predator. Homeopaths use sepia
to treat symptoms of apathy and weakness.
Also called flint, silica is used by homeopaths to
treat conditions that cause weakness, sweating,
and sensitivity to cold.
It is used to treat conditions with symptoms of itching,
burning pains, and odor.

Allium cepa

Apis

Arnica

Arsenicum
album

Belladonna

Bryonia

Calcarea
carbonica
Cantharis

Chamomilla

Ferrum
phosphoricum
Gelsemium

Hepar
sulphuris
Hypericum
Ignatia

Ipecac

Kali
bichromicum
Lachesis

Ledum
Lycopodium
Mercurius
vivus
Natrum
muriaticum
Nux vomica
Phosphorus
[Continued]

1832

Rhus
toxicodendron
Ruta
Sepia

Silica

Sulphur

medical schools, including Boston University and the
University of Michigan. However, with the formation
of the American Medical Association, which restricted
and closed down alternative practices, homeopathy
declined for half a century. When the 1960s invigorated back-to-nature trends and distrust of artificial
drugs and treatments, homeopathy began to grow
again dramatically through the next decades. In
1993, The New England Journal of Medicine reported
that 2.5 million Americans used homeopathic remedies and 800,000 patients visited homeopaths in 1990,
and it has continued to grow. Homeopathy is much
more popular in Europe than in the United States.
French pharmacies are required to make homeopathic
remedies available along with conventional medications. Homeopathic hospitals and clinics are part of
the national health system in Britain. It is also practiced in India and Israel, among other countries.
A visit to a homeopath can be a different experience than a visit to a regular physician. Surveys have
shown that homeopathic doctors spend much more
time during initial consultations than conventional
doctors spend. This is because a homeopath does a
complete case-taking to get a complete picture of a
person’s general health and lifestyle, as well as particular symptoms, on the physical, mental and emotional levels. Some symptoms can be so subtle that
the patient is not always completely aware of them,
and the doctor must spend time getting to know the
patient.
The initial visit often includes a long questionnaire about a patient’s medical and family history,
and then a long interview with the doctor, who
prompts the patient with many questions. Sometimes
GALE ENCYCLOPEDIA OF MEDICINE

The purpose of homeopathy is the restoration of
the body to homeostasis, or healthy balance, which
is its natural state. The symptoms of a disease are
regarded as the body’s own defensive attempt to correct its imbalance, rather than as enemies to be
defeated. Because a homeopath regards symptoms
as positive evidence of the body’s inner intelligence,
he or she will prescribe a remedy designed to stimulate
this internal curative process, rather than suppress the
symptoms.
In homeopathy, the curative process extends
beyond the relief of immediate symptoms of illness.
Healing may come in many stages, as the practitioner
treats layers of symptoms that are remnants of traumas or chronic disease in the patient’s past. This is part
of Hering’s Laws of Cure, named for Constantine
Hering, the father of homeopathy in America.
Hering believed that healing starts from the deepest
parts of the body to the extremities, and from the
upper parts of the body to the lower parts. Hering’s
Laws also state that homeopaths should treat disease
symptoms in reverse chronological order, from the
most recent to the oldest, restoring health in stages.
Sometimes, the patient may feel worse before feeling
better. This is called a healing crisis.
When prescribing a remedy, homeopaths will
match a patient’s symptoms with the proper remedy
in a repertory or materia medica that has been compiled throughout the history of homeopathy. Classical
homeopaths prescribe only one remedy at a time.
However, it is becoming more common, especially in
Europe, to use combination formulas of several remedies for the treatment of some combinations of
symptoms.
The cost of homeopathic care can vary. The cost
of visits will be comparable to conventional medicine,
with initial visits ranging from $50 to $300. Non-M.D.
homeopaths can charge from $50 to $250. Follow-up
visits are less, at about $35 to $100. Homeopathic
medicine is significantly cheaper than pharmaceuticals, and most remedies cost between $2 and $10.
Some doctors provide remedies without charge.
Homeopaths rarely use lab tests, which reduces the
cost of treatment further. In general, homeopathy is
much more economical than conventional medicine.
In 1991, the French government did a study on the
cost of homeopathic medicine, and found that it costs
half as much to treat patients, considering all costs
involved.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Aggravation—Temporary increase in symptoms
due to homeopathic remedy.
Antidote—Substance which cancels the effect of
homeopathic remedies
Homeopath—A homeopathic physician.
Proving—Case study of the effect of a homeopathic
medicine.
Repertory—Reference manual of homeopathic
remedies.
Vital force—Innate wisdom and energy of the
body.

When homeopaths are licensed professionals,
most insurance companies will pay for their fees.
Consumers should consult their insurance policies to
determine individual regulations. Insurance usually
will not cover homeopathic medicine, because it is
sold over-the-counter.

Precautions
Although homeopathic remedies sometimes use
substances that are toxic, they are diluted and prescribed in non-toxic doses. Remedies should be prescribed by a homeopathic practitioner. Those
preparing to take homeopathic remedies should also
avoid taking antidotes, substances which homeopathic
doctors believe cancel the effects of their remedies.
These substances include alcohol, coffee, prescription
drugs, peppermint (in toothpaste and mouthwash),
camphor (in salves and lotions), and very spicy
foods. Homeopathic medicine should also be handled
with care, and should not be touched with the hands or
fingers, which can contaminate it.

Side effects
A homeopathic aggravation sometimes occurs
during initial treatment with homeopathic remedies.
This means that symptoms can temporarily worsen
during the process of healing. Although this is usually
mild, the aggravation can sometimes be severe.
Homeopaths see aggravation as a positive sign that
the remedy is a good match for the patient’s symptoms. The healing crisis, which happens when the
patient is undergoing treatment for layers of symptoms, may also cause the patient to feel worse before
feeling better. Some patients can experience emotional
1833

Homeopathic medicine

a homeopathic doctor will use lab tests to establish a
patient’s general level of health. The initial interview
usually lasts between one and two hours.

Homeopathic medicine, acute prescribing

disturbances like weeping or depression, if suppressed
emotional problems led to the illness in the first place.

Research and general acceptance
Since the early 1900s, when the American Medical
Association and pharmacists waged a battle against
it, homeopathy has been neglected and sometimes
ridiculed by mainstream medicine. Aside from politics, part of the reason for this is that there are some
aspects of homeopathy which have not been completely explained scientifically. For instance, homeopaths have found that the more they dilute and succuss
a remedy, the greater effect it seems to have on the body.
Some homeopathic remedies are so diluted that not
even a single molecule of the active agent remains in
a solution, yet it still works; studies have demonstrated
this paradox, yet can’t explain it. Also, homeopathy
puts an emphasis on analyzing symptoms and then
applying remedies to these symptoms, rather than
working by classifying diseases. Thus, some people
with the same disease may require different homeopathic medicines and treatments. Furthermore, conventional medicine strives to find out how medicines
work in the body before they use them; homeopathy
is less concerned with the intricate biochemistry
involved than with whether a remedy ultimately
works and heals holistically. For all these reasons,
conventional medicine claims that homeopathy is not
scientific, but homeopaths are quick to reply that
homeopathy has been scientifically developed and
studied for centuries, with much documentation and
success.
There continue to be many studies that affirm the
effectiveness of homeopathic treatments. Among the
most celebrated, the British Medical Journal in 1991
published a large analysis of homeopathic treatments
that were given over the course of 25 years. This
project involved over 100 studies of patients with
problems ranging from vascular diseases, respiratory
problems, infections, stomach problems, allergies,
recovery from surgeries, arthritis, trauma, psychological problems, diabetes, and others. The study found
improvement with homeopathic treatment in most
categories of problems, and concluded that the evidence was ‘‘sufficient for establishing homeopathy
as a regular treatment for certain indications.’’
Resources
PERIODICALS

Homeopathy Today. 801 N. Fairfax St. #306,Alexandria, VA
22314. (703) 548-7790.
Similimum. P.O. Box 69565, Portland, OR 97201. (503)
795-0579.
1834

OTHER

Ayurvedic Institute. <http://www.ayurveda.com>.
National Center for Homeopathy. <http://www.healthy.
net/nch>.
North American Society of Homeopaths.
<http://www.homeopathy.org>.

Homeopathic medicine, acute
prescribing
Definition
Acute homeopathic prescribing is that part of
homeopathy that treats illness which has an abrupt
onset and needs immediate attention. In homeopathic
medicine, acute refers primarily to the speed of onset
and self-limiting character of the disorder rather than
its seriousness. Colds, influenza, sore throats, insect
stings, cuts, bruises, vomiting, diarrhea, fever, muscle
aches, and short-term insomnia are all examples of
conditions that are treated by acute prescribing. The
remedies given in acute homeopathic prescribing are
intended to stimulate the body’s internal ability to heal
itself; they do not kill germs or suppress symptoms.
Acute prescribing can be done—within limits—by
patients at home, as well as by homeopathic practitioners. Study courses, self-treatment guides, and
homeopathic home medicine kits are now available
by mail order from homeopathic pharmacies and educational services.

Purpose
Homeopathic physicians seek to cure their
patients on physical, mental, and emotional levels,
and each treatment is tailored to a patient’s individual
needs. Homeopathy is generally a safe treatment, as it
uses medicines in extremely diluted quantities, and
there are usually minimal side effects. Its non-toxicity
makes it a good choice for the treatment of children.
Another benefit of homeopathy is the cost of treatments; homeopathic remedies are inexpensive, often a
fraction of the cost of conventional drugs.
Acute homeopathic prescribing is thought to benefit a wide range of ailments. These include altitude
sickness, Bell’s palsy, the common cold, allergies, coughing, dengue fever, dysentery, earaches, migraine headaches, fever, food poisoning, grief, influenza, motion
sickness, shock, sore throat, surgical complications,
and reactions to vaccinations and drug therapy.
Acute remedies may also be prescribed to treat insect
GALE ENCYCLOPEDIA OF MEDICINE

Description
Origins
Homeopathy is a gentle, painless, holistic system
of healing developed during the 1790s by Samuel
Hahnemann, a German physician. Experimenting on
himself with the anti-malarial drug quinine,
Hahnemann noticed that large doses of the medicine
actually caused malaria-like symptoms, while smaller
doses cured the symptoms. From this, he advanced his
concept of Similia similibus curentur, or ‘‘let like be
cured with like.’’ Hahnemann then developed an
extensive system of medicine based on this concept.
He named it homeopathy, from the Greek words
homoios (the same) and pathos (suffering).
Homeopathic remedies are almost always made
from natural materials—plant, animal, or mineral
substances—that have been treated to form mother
tinctures or nonsoluble powders. Liquid extracts are
then potentized, or increased in power, by a series
of dilutions and succussions, or shakings. It is thought
that succussion is necessary to transfer the energy
of the natural substance to the solution. In addition,
the potency of the remedy is regarded as increasing
with each dilution. After the tincture has been diluted
to the prescribed potency, the resulting solution is
added to a bottle of sucrose/lactose tablets, which are
stored in a cool, dark place. If the remedy is not
soluble in water, it is ground to a fine powder and
triturated with powdered lactose to achieve the desired
potency.
Proponents of homeopathy over the years have
included Louisa May Alcott, Charles Dickens,
Benjamin Disraeli, Johann Wolfgang Goethe,
Nathaniel Hawthorne, William James, Henry
Wadsworth Longfellow, Pope Pius X, John D.
Rockefeller, Harriet Beecher Stowe, William
Thackeray, Daniel Webster, and W. B. Yeats.
England’s Royal Family has employed homeopathic
practitioners since the 1830s.
Homeopathic prescribing differs in general from
allopathic medicine in its tailoring of remedies to the
patient’s overall personality type and totality of symptoms, rather than to the disease. Whereas a conventional physician would prescribe the same medication
GALE ENCYCLOPEDIA OF MEDICINE

or treatment regimen to all patients with the common
cold, for example, a homeopathic practitioner would
ask detailed questions about each patient’s symptoms
and the modalities, or factors, that make them better
or worse. As a result, the homeopath might prescribe
six different remedies for six different patients with
the same illness. In acute prescribing homeopathy,
consultations are more brief compared to constitutional homeopathic prescribing. A typical patient
might spend just 10–15 minutes with the practitioner,
compared to more than an hour for constitutional
prescribing.
Homeopathic classification of symptoms
Homeopathic practitioners use the word symptom in a more inclusive fashion than traditional
medicine. In homeopathy, symptoms include any
change that the patient experiences during the illness,
including changes in emotional or mental patterns.
Homeopaths classify symptoms according to a
hierarchy of four categories for purposes of acute
prescribing:


Peculiar symptoms. These are symptoms unique to
the individual that do not occur in most persons with
the acute disease. Homeopaths make note of peculiar
symptoms because they often help to determine the
remedy.



Mental and emotional symptoms. These are important general symptoms that inform the homeopath
about the patient’s total experience of the disorder.



Other general symptoms. These are physical symptoms felt throughout the patient’s body, such as
tiredness, changes in appetite, or restlessness.



Particular symptoms. Particular symptoms are localized in the body; they include such symptoms as
nausea, skin rashes, headache, etc.

During homeopathic case-taking, the practitioner
will evaluate the intensity of the patient’s symptoms,
assess their depth within the patient’s body, note any
peculiar symptoms, evaluate the modalities of each
symptom, and make a list of key symptoms to guide
the selection of the proper medicine.
Homeopathic remedies
There are several hundred homeopathic remedies. Homeopathic medicines are usually formulated
from diluted or triturated natural substances, including plants, minerals, or even venom from snakes or
stinging insects. Some remedies may be given in a
spray, ointment, or cream, but the most common
1835

Homeopathic medicine, acute prescribing

stings, animal bites, and problems related to poison
oak and poison ivy. It may be further employed in
treating injuries including black eyes, burns, bruises,
concussions, cuts, damaged tendons and ligaments,
dislocations, fractures, herniated discs, nosebleeds,
puncture wounds, sprains, and strains.

Homeopathic medicine, acute prescribing

forms of administration are liquid dilutions and two
sizes of pellets, or cylindrical tablets (for triturated
remedies). A dose consists of one drop of liquid; 10–
20 small pellets; or 1–3 large pellets. Since the remedies are so dilute, the exact size of the dose is not
of primary importance. The frequency of dosing is
considered critical, however; patients are advised
not to take further doses until the first has completed
its effect.
Homeopathic remedies can be kept indefinitely
with proper handling. Proper handling includes storing the remedies in the original bottles and discarding
them if they become contaminated by sunlight or other
intense light; temperatures over 100  F (37.8  C);
vapors from camphor, mothballs, or perfume; or
from other homeopathic remedies being opened in the
same room at the same time.

Preparations
Case-taking
The first step in acute prescribing is a lengthy
interview with the patient, known as case-taking. In
addition to noting the character, location, and severity
of the patient’s symptoms, the homeopath will ask
about their modalities. The modalities are the circumstances or factors (e.g., weather, time of day, body
position, behavior or activity, etc.) that make the
symptoms either better or worse. Case-taking can be
done by the patient or a family member as well as by a
homeopath.
Selection and administration of a remedy
The choice of a specific remedy is guided by the
patient’s total symptom profile rather than by the illness. Homeopathic remedies are prescribed according
to the law of similars, which holds that a substance
that produces specific symptoms in healthy people
cures those symptoms in sick people when given in
highly diluted forms. For example, a patient with
influenza who is irritable, headachy, and suffering
from joint or muscle pains is likely to be given bryonia
(wild hops), because this plant extract would cause this
symptom cluster in a healthy individual.
Patients are instructed to avoid touching homeopathic medicines with their fingers. The dose can be
poured onto a piece of white paper or the bottle’s cap
and tipped directly into the mouth. Homeopathic
remedies are not taken with water; patients should
not eat or drink anything for 15–20 minutes before
or after taking the dose.
1836

Precautions
Homeopathic acute prescribing is not recommended for the treatment of chronic conditions
requiring constitutional prescribing, for severe infections requiring antibiotic treatment, or for conditions
requiring major surgery. It is also not recommended
for the treatment of mental health problems.
Persons who are treating themselves with homeopathic remedies should follow professional guidelines
regarding the limitations of home treatment. Most
homeopathic home treatment guides include necessary
information regarding symptoms and disorders that
require professional attention.
Homeopathic remedies may lose their potency if
used at the same time as other products. Some homeopathic practitioners recommend the avoidance of mint
and mentholated products (toothpastes, candies,
chewing gum, mouth rinses), as well as camphor and
camphorated products (including eucalyptus and
Tiger Balm), patchouli and other essential oils, moth
balls, strong perfumes, aftershaves, scented soaps,
stress, x rays, coffee, nicotine, recreational drugs
(marijuana) and certain therapeutic drugs (most notably
cortisone and prednisone) during treatment. Patients
are also advised to avoid electric blankets and dental
work, as these are thought to adversely affect homeopathic therapy. Homeopathic remedies should never
be placed near magnets.
Practitioners caution that high-potency preparations should be used only under the supervision of a
homeopathic practitioner.

Side effects
Homeopathic medicines are so diluted that sometimes no trace of the original substance can be
detected. These medicines are therefore considered
non-toxic and generally free of harmful side effects.
There may, however, be individual reactions to homeopathic medicine.
An intensified healing response may occur as
treatment begins, which causes symptoms to worsen,
but the phenomenon is temporary. In some patients,
old symptoms may re-appear from past conditions
from which recovery was not complete. Such phenomena are taken as positive indications that the healing
process has commenced.

Research and general acceptance
As Samuel Hahnemann’s healing system grew in
popularity during the 1800s, it quickly attracted
GALE ENCYCLOPEDIA OF MEDICINE

There continue to be many studies that affirm
the effectiveness of homeopathic treatments. Among
the most celebrated, the British Medical Journal
in 1991 published a large analysis of homeopathic
treatments that were given over the course of 25
years. This project involved over 100 studies of
patients with problems ranging from vascular diseases, respiratory problems, infections, stomach
problems, allergies, recovery from surgeries, arthritis, trauma, psychological problems, diabetes, and
others. The study found improvement with homeopathic treatment in most categories of problems,
and concluded that the evidence was ‘‘sufficient for
establishing homeopathy as a regular treatment for
certain indications.’’
In the United Kingdom and other countries where
homeopathy is especially popular, some medical
doctors incorporate aspects of acute prescribing
homeopathy into their practices. Countries in
which homeopathy is popular include France,
India, Pakistan, Sri Lanka, Brazil, and Argentina.
Large homeopathic hospitals exist in London and
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Acute prescribing—Homeopathic treatment for
self-limiting illnesses with abrupt onset.
Allopathy—Conventional medical treatment of
disease symptoms that uses substances or techniques to oppose or suppress the symptoms.
Law of similars—The basic principle of homeopathic medicine that governs the selection of a
specific remedy. It holds that a substance of natural
origin that produces certain symptoms in a healthy
person will cure those same symptoms in a sick
person.
Modalities—The factors and circumstances that
cause a patient’s symptoms to improve or worsen.
Mother tincture—The first stage in the preparation
of a homeopathic remedy, made by soaking a
plant, animal, or mineral product in a solution of
alcohol.
Potentization—The process of increasing the
power of homeopathic preparations by successive
dilutions and succussions of a mother tincture.
Succussion—The act of shaking diluted homeopathic remedies as part of the process of
potentization.
Trituration—The process of diluting a nonsoluble
substance for homeopathic use by grinding it to a
fine powder and mixing it with lactose powder.

Glasgow, and homeopathic medical centers can be
found in India and South America.
Resources
BOOKS

Strohecker, James. Alternative Medicine: The Definitive
Guide. Tiburon, Calif.: Future Medicine Publishing,
Inc., 1999.
ORGANIZATIONS

The American Institute of Homeopathy. 1585 Glencoe,
Denver, CO 80220. (303) 898-5477.
Council for Homeopathic Certification. P.O. Box 157, Corte
Madera, CA 94976.
International Foundation for Homeopathy. 2366 Eastlake
Avenue East, #301, Seattle, WA 98102. (425)
776-4147.
National Center for Homeopathy. 801 North Fairfax Street,
Suite 306, Alexandria, VA 22134. (703) 548-7790.
North American Society of Homeopaths. 10700 Old County
Rd. 15, #350, Minneapolis, MN 55441. (612)
593-9458.
1837

Homeopathic medicine, acute prescribing

vehement opposition from the medical and apothecary professions. Since the early 1900s, when the
American Medical Association and pharmacists
waged a battle against it, homeopathy has been
neglected and sometimes ridiculed by mainstream
medicine. Aside from politics, part of the reason
for this is that there are some aspects of homeopathy which have not been completely explained
scientifically. For instance, homeopaths have
found that the more they dilute and succuss a
remedy, the greater effect it seems to have on the
body. Some homeopathic remedies are so diluted
that not even a single molecule of the active agent
remains in a solution, yet homeopaths maintain it
still works; some studies have demonstrated this
paradox, yet cannot explain it. Also, homeopathy
puts an emphasis on analyzing symptoms and then
applying remedies to these symptoms, rather than
working by classifying diseases. Thus, some people
with the same disease may require different homeopathic medicines and treatments. Furthermore, conventional medicine strives to find out how
medicines work in the body before they use them;
homeopathy is less concerned with the intricate
biochemistry involved than with whether a remedy
ultimately works and heals holistically. For all these
reasons, conventional medicine claims that homeopathy is not scientific, but homeopaths are quick
to reply that homeopathy has been scientifically
developed and studied for centuries, with much
documentation and success.

Homeopathic medicine, constitutional prescribing

Homeopathic medicine,
constitutional prescribing
Definition
Constitutional homeopathic prescribing, also
called classical prescribing, is a holistic system of
medicine that has been practiced for more than
200 years. Unlike acute homeopathic prescribing, constitutional prescribing refers to the selection and
administration of homeopathic preparations over a
period of time for treatment related to what practitioners call miasmic disorders, those caused by an
inherited predisposition to a disease. The term miasm
comes from a Greek word meaning stain or pollution.
As in acute prescribing, constitutional prescribing
is holistic in that it is intended to treat the patient
on the emotional and spiritual levels of his or her
being as well as the physical. Constitutional prescribing is also aimed at eventual cure of the patient, not
just suppression or relief of immediate symptoms.

Purpose
Homeopathic physicians seek to cure their
patients on physical, mental, and emotional levels,
and each treatment is tailored to a patient’s individual
needs. Homeopathy is generally a safe treatment, as it
uses medicines in extremely diluted quantities, and
there are usually minimal side effects. Its non-toxicity
makes it a good choice for the treatment of children.
Another benefit of homeopathy is the cost of treatments; homeopathic remedies are inexpensive, often
a fraction of the cost of conventional drugs.
Classical homeopathy has been used to treat a wide
range of diseases and conditions, most of which tend
to be long-term. These include: alcoholism, allergies,
anxiety, arthritis, asthma, bladder conditions, chronic
fatigue syndrome, depression, drug dependencies, gastrointestinal problems, Gulf War sickness, headache,
hearing problems, herpes, hypersensitivity, immune
disorders, insomnia, joint problems, kidney conditions,
liver problems, Lyme disease, lower back problems,
malaria, menopause, menstrual problems, migraine,
multiple sclerosis, paralysis, phobias, shingles, sinus
problems, skin disorders, repetitive stress injury, rheumatism, vertigo, vision problems, and yeast infections.

Description
Origins
by

Homeopathy was developed during the 1790s
Samuel Hahnemann, a German physician.

1838

Experimenting on himself with the anti-malarial drug
quinine, Hahnemann noticed that large doses of the
medicine actually caused malaria-like symptoms,
while smaller doses cured the symptoms. From this,
he advanced his concept of Similia similibus curentur,
or ‘‘let like be cured with like.’’ Hahnemann then
developed an extensive system of medicine based on
this concept. He named it homeopathy, from the Greek
words homoios (the same) and pathos (suffering).
There are several hundred homeopathic remedies. They are almost always made from natural
materials—plant, animal, or mineral substances—
that have been treated to form mother tinctures or
nonsoluble powders. Liquid extracts are then potentized, or increased in power, by a series of dilutions
and succussions, or shakings. It is thought that
succussion is necessary to transfer the energy of the
natural substance to the solution. In addition, the
potency of the remedy is regarded as increasing
with each dilution. After the tincture has been
diluted to the prescribed potency, the resulting solution is added to a bottle of sucrose/lactose tablets,
which are stored in a cool, dark place. If the remedy
is not soluble in water, it is ground to a fine powder
and triturated with powdered lactose to achieve the
desired potency.
Proponents of homeopathy over the years have
included Louisa May Alcott, Charles Dickens,
Benjamin Disraeli, Johann Wolfgang Goethe,
Nathaniel Hawthorne, William James, Henry
Wadsworth Longfellow, Pope Pius X, John D.
Rockefeller, Harriet Beecher Stowe, William
Thackeray, Daniel Webster, and W. B. Yeats.
England’s Royal Family has employed homeopathic
practitioners since the 1830s.
Constitutional prescribing is based on the
patient’s symptom profile and specific aspects of
homeopathic theory.
Homeopathic classification of symptoms
Homeopathic practitioners use the word symptom in a more inclusive fashion than traditional medicine. In homeopathy, symptoms include any change
that the patient experiences during the illness, including changes in emotional or mental patterns.
Homeopaths classify symptoms according to a
hierarchy of four categories:


Peculiar symptoms. These are symptoms unique to
the individual that do not occur in most persons.
Homeopaths make note of peculiar symptoms
because they often help to determine the remedy.
GALE ENCYCLOPEDIA OF MEDICINE

Mental and emotional symptoms. These are important general symptoms that inform the homeopath
about the patient’s total experience of the disorder.



Other general symptoms. These are physical symptoms felt throughout the patient’s body, such as
tiredness, changes in appetite, or restlessness.



Particular symptoms. Particular symptoms are localized in the body; they include such symptoms as
nausea, skin rashes, or headaches.
Miasms

Homeopaths regard the patient’s symptom profile
as a systemic manifestation of an underlying chronic
disorder called a miasm. Miasms are serious disturbances of what homeopaths call the patient’s vital
force that are inherited from parents at the time of
conception. Hahnemann believed that the parents’
basic lifestyle, their emotional condition and habitual
diet, and even the atmospheric conditions at the time
of conception would affect the number and severity of
miasms passed on to the child. Hahnemann himself
distinguished three miasms: the psoric, which he considered the most universal source of chronic disease
in humans; the syphilitic; and the sycotic, which he
attributed to gonorrhea. Later homeopaths identified
two additional miasms, the cancernic and the tuberculinic. The remaining major source of miasms is
allopathic medicine. It is thought that specific allopathic treatments—particularly smallpox vaccinations, cortisone preparations, major tranquilizers,
and antibiotics—can produce additional layers of
miasms in the patient’s constitution. Constitutional
prescribing evaluates the person’s current state or
miasmic picture, and selects a remedy intended to
correct or balance that state. The homeopath may
prescribe a different remedy for each miasmic layer
over time, but gives only one remedy at a time directed
at the person’s current state. The basic principle
governing the prescription of each successive remedy
is the law of similars, or ‘‘like cures like.’’
Hering’s laws of cure
The homeopathic laws of cure were outlined
by Constantine Hering, a student of Hahnemann
who came to the United States in the 1830s. Hering
enunciated three laws or principles of the patterns of
healing that are used by homeopaths to evaluate the
effectiveness of specific remedies and the overall
progress of constitutional prescribing:


Healing progresses from the deepest parts of the
organism to the external parts. Homeopaths consider the person’s mental and emotional dimensions,

GALE ENCYCLOPEDIA OF MEDICINE

together with the brain, heart, and other vital organs,
as a person’s deepest parts. The skin, hands, and feet
are considered the external parts.


Symptoms appear or disappear in the reverse of their
chronological order of appearance. In terms of constitutional treatment, this law means that miasms
acquired later in life will resolve before earlier ones.



Healing proceeds from the upper to the lower parts
of the body.
Healing crises

Homeopaths use Hering’s laws to explain the
appearance of so-called healing crises, or aggravations, in the course of homeopathic treatment. It is
not unusual for patients to experience temporary
worsening of certain symptoms after taking their
first doses of homeopathic treatment. For example, a
person might notice that arthritic pains in the
shoulders are better but that the hands feel worse.
Hering’s third law would indicate that the remedy is
working because the symptoms are moving downward
in the body. In constitutional prescribing, a remedy
that removes one of the patient’s miasmic layers
will then allow the symptoms of an older miasm to
emerge. Thus the patient may find that a physical
disease is followed by a different set of physical problems or by emotional symptoms.

Preparations
The most important aspects of preparation for
constitutional prescribing are the taking of a complete
patient history and careful patient education.
Case-taking
Homeopathic case-taking for constitutional prescribing is similar to that for acute prescribing, but
more in-depth. The initial interview generally takes
one to two hours. The practitioner is concerned with
recording the totality of the patient’s symptoms and
the modalities that influence their severity. Also
included are general characteristics about the patient
and his or her lifestyle choices. For example, a practitioner might ask the patient if he or she likes being
outside or is generally hot or cold. There is also an
emphasis on the patient’s lifetime medical history,
particularly records of allopathic treatments.
Patient education
Homeopaths regard patients as equal partners
in the process of recovery. They will take the time
to explain the theories underlying constitutional
1839

Homeopathic medicine, constitutional prescribing



Homeopathic medicine, constitutional prescribing

prescribing to the patient as well as taking the history.
Patient education is especially important in constitutional prescribing in order to emphasize the need
for patience with the slowness of results and length
of treatment, and to minimize the possibility of selftreatment with allopathic drugs if the patient has a
healing crisis.
Homeopathic remedies
In constitutional prescribing, one dose of the
selected remedy is given. Patients then wait two to six
weeks before following up with the homeopath, while
the body begins the healing process. At the follow-up
visit, the remedy may be repeated, or a different
remedy prescribed. The preparation, selection, administration, and storage of remedies for constitutional
prescribing are the same as for acute prescribing.
These procedures are described more fully in the article on acute prescribing.

Precautions
Constitutional homeopathic prescribing is not
appropriate for diseases or health crises requiring
emergency treatment, whether medical, surgical, or
psychiatric. In addition, constitutional prescribing
should not be self-administered. Although home treatment kits of homeopathic remedies are available for
acute self-limited disorders, the knowledge of homeopathic theory and practice required for constitutional
evaluation is beyond the scope of most patients.
Patients are instructed to avoid touching homeopathic medicines with their fingers. The dose can be
poured onto a piece of white paper or the bottle’s cap
and tipped directly into the mouth. Homeopathic
remedies are not taken with water; patients should
not eat or drink anything for 15–20 minutes before
or after taking the dose.
Homeopathic remedies may lose their potency if
used at the same time as other products. Some homeopathic practitioners recommend the avoidance of mint
and mentholated products (toothpastes, candies,
chewing gum, mouth rinses), as well as camphor and
camphorated products (including eucalyptus and
Tiger Balm), patchouli and other essential oils, moth
balls, strong perfumes, aftershaves, scented soaps,
stress, x rays, coffee, nicotine, recreational drugs (marijuana) and certain therapeutic drugs (most notably
cortisone and prednisone) during treatment. Patients
are also advised to avoid electric blankets and dental
work, as these are thought to adversely affect homeopathic therapy. Homeopathic remedies should never
be placed near magnets.
1840

Side effects
Homeopathic medicines are so diluted that sometimes no trace of the original substance can be
detected. These medicines are therefore considered
non-toxic and generally free of harmful side effects.
The primary risks to the patient from constitutional
homeopathic treatment are the symptoms of the
healing crisis and individual reactions to homeopathic
medicine. The complexity of constitutional prescribing
requires homeopaths to have detailed knowledge of
the materia medica and the repertories, and to take
careful and extensive case notes.
An intensified healing response may occur as
treatment begins, which causes symptoms to worsen,
but the phenomenon is temporary. In some patients,
old symptoms may re-appear from past conditions
from which recovery was not complete. Such phenomena are taken as positive indications that the healing
process has commenced.

Research and general acceptance
As Samuel Hahnemann’s healing system grew
in popularity during the 1800s, it quickly attracted
vehement opposition from the medical and apothecary
professions. Since the early 1900s, when the American
Medical Association and pharmacists waged a battle
against it, homeopathy has been neglected and sometimes ridiculed by mainstream medicine. Aside from
politics, part of the reason for this is that there are
some aspects of homeopathy which have not been
completely explained scientifically. For instance,
homeopaths have found that the more they dilute and
succuss a remedy, the greater effect it seems to have on
the body. Some homeopathic remedies are so diluted
that not even a single molecule of the active agent
remains in a solution, yet homeopaths maintain it still
works; some studies have demonstrated this paradox,
yet cannot explain it. Also, homeopathy puts an
emphasis on analyzing symptoms and then applying
remedies to these symptoms, rather than working by
classifying diseases. Thus, some people with the same
disease may require different homeopathic medicines
and treatments. Furthermore, conventional medicine
strives to find out how medicines work in the body
before they use them; homeopathy is less concerned
with the intricate biochemistry involved than with
whether a remedy ultimately works and heals holistically. For all these reasons, conventional medicine
claims that homeopathy is not scientific, but homeopaths are quick to reply that homeopathy has been
scientifically developed and studied for centuries, with
much documentation and success.
GALE ENCYCLOPEDIA OF MEDICINE

Aggravation—Another term used by homeopaths
for the healing crisis.
Allopathy—Conventional medical treatment of disease symptoms that uses substances or techniques
to oppose or suppress the symptoms.
Constitutional prescribing—Homeopathic treatment for long-term or chronic disorders related
to inherited predispositions to certain types of
illnesses.
Healing crisis—A temporary worsening of the
patient’s symptoms during successive stages of
homeopathic treatment.
Law of similars—The basic principle of homeopathic medicine that governs the selection of a
specific remedy. It holds that a substance of natural
origin that produces certain symptoms in a healthy
person will cure those same symptoms in a sick
person.
Laws of cure—A set of three rules used by homeopaths to assess the progress of a patient’s recovery.
Materia medica—In homeopathy, reference books
compiled from provings of the various natural
remedies.
Miasm—In homeopathic theory, a general weakness
or predisposition to chronic disease that is transmitted down the generational chain.
Modalities—The factors and circumstances that
cause a patient’s symptoms to improve or worsen,
including weather, time of day, effects of food, and
similar factors.
Repertories—Homeopathic reference books consisting of descriptions of symptoms. The process of
selecting a homeopathic remedy from the patient’s
symptom profile is called repertorizing.

There continue to be many studies that affirm the
effectiveness of homeopathic treatments. Among the
most celebrated, the British Medical Journal in 1991
published a large analysis of homeopathic treatments
that were given over the course of 25 years. This
project involved over 100 studies of patients with
problems ranging from vascular diseases, respiratory
problems, infections, stomach problems, allergies,
recovery from surgeries, arthritis, trauma, psychological problems, diabetes, and others. The study found
improvement with homeopathic treatment in most
GALE ENCYCLOPEDIA OF MEDICINE

categories of problems, and concluded that the
evidence was ‘‘sufficient for establishing homeopathy
as a regular treatment for certain indications.’’
In the United Kingdom and other countries where
homeopathy is especially popular, some medical
doctors incorporate aspects of acute prescribing
homeopathy into their practices. Countries in which
homeopathy is popular include France, India, Pakistan,
Sri Lanka, Brazil, and Argentina. Large homeopathic
hospitals exist in London and Glasgow, and homeopathic medical centers can be found in India and
South America.
Resources
BOOKS

Strohecker, James. Alternative Medicine: The
DefinitiveGuide. Tiburon, Calif.: Future Medicine
Publishing, Inc.,1999.
ORGANIZATIONS

American Institute of Homeopathy. 1585 Glencoe, Denver,
CO 80220. (303) 898-5477.
Council for Homeopathic Certification. P.O. Box 157, Corte
Madera, CA 94976.
International Foundation for Homeopathy. 2366 Eastlake
Avenue East, #301, Seattle, WA 98102. (425) 776-4147.
National Center for Homeopathy. 801 North Fairfax Street,
Suite 306, Alexandria, VA 22134. (703) 548-7790.
North American Society of Homeopaths. 10700 Old County
Rd. 15, #350, Minneapolis, MN 55441. (612) 593-9458.

Homocysteine
Definition
Homocysteine is a naturally occurring amino
acid found in blood plasma. High levels of homocysteine in the blood are believed to increase the chance
of heart disease, stroke, Alzheimer’s disease, and
osteoporosis.

Description
Homocysteine is a sulfur-containing amino acid
that occurs naturally in all humans. It is broken down
in the body through two metabolic pathways. The
chemical changes that must occur to break down
homocysteine require the presence of folic acid (also
called folate) and vitamins B6 and B12. The level of
homocysteine in the blood is influenced by the presence of these substances.
1841

Homocysteine

KEY TERMS

Homocysteine

Homocystinuria is a rare genetic disorder that
occurs in about one in every 200,000 individuals.
This congenital metabolic disorder causes large
amounts of homocysteine to be excreted in the urine.
Homocystinuria is associated mental retardation and
the development of heart disease before age 30.
In the late 1960s, doctors documented that individuals with homocystinuria developed narrowing of
the arteries at a very early age, sometimes even in
childhood. Although homocystinuria is rare, this finding stimulated research on whether people who did not
have homocystinuria but who did have unusually high
levels of homocysteine in their blood were at greater
risk of developing heart disease or stroke.
Many risk factors, including family history of heart
disease, smoking, obesity, lack of exercise, diabetes,
high levels of low-density lipoprotein cholesterol
(LDL or ‘‘bad’’ cholesterol), low levels of high-density
lipoprotein cholesterol (HDL or ‘‘good’’ cholesterol),
and high blood pressure have been documented to
increase the risk of stroke and heart disease. With so
many other risk factors, it has been difficult to determine whether high levels of homocysteine are an
independent risk factor for the development these diseases. However, a substantial number of controlled,
well-designed, and well-documented studies have
shown that individuals who have high levels of homocysteine in the blood are at increased risk of developing
blocked blood vessels, a condition known as occlusive
arterial disease or at risk to worsen atherosclerosis
(‘‘hardening of the arteries’’).
In the 2000s, studies also suggested that high levels
of homocysteine were associated with poorer mental
functioning, leading to ongoing investigations into
the role of homocysteine in Alzheimer’s disease.
Additional studies have also suggested that high levels
of homocysteine can lead to osteoporosis and an
increased risk of broken bones in the elderly. As of
2005, homocysteine was being tested in half a dozen
clinical trials to determine its role in these and several
other conditions. Information on clinical trials that
are enrolling patients can be found on-line at
<http://www.clinicaltrials.gov>.

Causes and symptoms
Homocysteine is thought to irritate the lining of
the blood vessels causing them to become scarred,
hardened, and narrowed. This increases the work the
heart must do, leading to heart disease. High levels of
homocysteine also cause increased blood clotting.
Blood clots can decrease or block the flow of blood
through blood vessels, resulting in strokes and heart
1842

attacks. If and how homocysteine directly plays a
role in osteoporosis and Alzheimer’s disease is not
clear as of 2005.
The level of homocysteine in the blood naturally
varies with age, gender, diet, hereditary factors, and
general health, but it is estimated that 5–10% of the
population has homocysteine levels that are considered high. With the exception of rare individuals who
have congenital homocystinuria, people with high
blood levels of homocysteine do not have any obvious
signs or symptoms.

Diagnosis
The American Heart Association and the
American College of Cardiology do not recommend
routine screening of homocysteine levels, but they do
recommend screening as part of a cardiac risk assessment for individuals who have a family history of
coronary artery disease but no obvious symptoms of
heart disease. The level of homocysteine in the blood
can be measured with a simple blood test that is often,
but not always, done after fasting. Homocysteine
levels of 12 mmol/L are considered normal and levels
below 10 mmol/L are considered desirable.

Treatment
Lowering homocysteine blood levels is linked
to increasing the intake of folic acid and vitamins
B6 and B12. The healthiest way to increase intake is
by eating more foods that are high in these substances. Good sources of folic acid, vitamin B6 and
B12 include green leafy vegetables, fortified breakfast
cereals, lentils, chickpeas, asparagus, spinach, and
most beans. Taking a daily multivitamin is also a
way to increase the levels of these substances.
However, megadoses of folic acid, vitamin B6 and
B12 are not recommended. Individuals should discuss dosage with their doctor before beginning any
supplements. It is important to note that a direct link
between increased intake of folic acid, vitamin B6,
and vitamin B12 and decreased incidence stroke and
heart attack has not been proved. However, one
study published in the Journal of the American
Medical Association found that women whose folic
acid levels were in the lowest 25% were 69% more
likely to die of coronary problems than women
whose folic acid levels were in the top 25%.
Individuals with homocystinuria are treated with
the drug betaine (Cystadane). This is a powder dissolved in water, juice, or milk and drunk usually twice
a day with meals. This drug is not normally used
GALE ENCYCLOPEDIA OF MEDICINE

Alzheimer’s disease—A degenerative brain disease
of unknown origin that is a common cause of
dementia in older individuals.
Amino acid—A nitrogen-containing building block
of protein molecules.
Androgens—Male sex hormones.
Congenital—Present at birth.
Osteoporosis—Loss of minerals from the bones,
causing bones to break more easily.
Plasma—The liquid part of the blood in which cells
are suspended.

McLean, Robert R., et al. ‘‘Homocysteine as a Predictive
Factor for Hip Fracture in Older Persons.’’ New
England Journal of Medicine, 350 (May 13, 2004):
2042–49 [cited 23 March 2005]. <http://content.nejm.
org/cgi/content/abstract/350/20/2042>.
Morey, Sharon S. ‘‘Practice Guidelines: AHA and ACC
Outline Approaches to Coronary Disease Risk
Assessment.’’ American Family Physician, 61, no. 8
(April 15, 2000): 2534–44 [cited March 23, 2005].
<http://www.aafp.org/afp/2000415/practice.html>.
ORGANIZATIONS

American Heart Association. 7272 Greenville Ave., Dallas,
TX 75231. (800)242-8721.
<http://www.americanheart.org>.
OTHER

Homocysteine.net, May 10, 2004. [cited March 23, 2005].
<http://www.homocysteine.net>

simply to lower high levels of homocysteine in the
absence of congenital disease.

Prognosis
Individuals who increase the folic acid, vitamin B6
and B12 in their diet are expected to see a decrease in
blood levels of homocysteine and as a result decrease
their risk of heart disease and stroke.

Prevention
Certain drugs are suspected of increasing the level
of homocysteine in the blood. People using these drugs
should discuss with their doctor the advisability of
increasing their intake of folic acid, vitamin B6, and
vitamin B12. These drugs include:


lipid-lowering drugs such as fenofibrate (Tricor) and
bezafibrate (Bezalip)



metformin (Glucophage), a drug to modify insulin
resistance



anti-epileptic drugs such as phenobarbital, phenytoin (Dilantin), primidone (Mysoline) and carbamazepine (Tegretol)



levadopa (Sinemet) for treatment of Parkinson’s disease



methotrexate (Rheumatrex, Trexall) for treatment of
cancer, psoriasis, rheumatoid arthritis, and systemic
lupus erythematosus



androgen treatment



nitrous oxide (‘‘laughing gas’’), a mild anesthetic

Resources
BOOKS

McCully, Kilmer S. The Homocysteine Revolution. 2nd ed.
New York: McGraw Hill 1999.
GALE ENCYCLOPEDIA OF MEDICINE

Tish Davidson, A.M.

Hong Kong flu see Influenza

Hookworm disease
Definition
Hookworm disease is an illness caused by one of
two types of S-shaped worms that infect the intestine
of humans (the worm’s host).

Description
Two types of hookworm are responsible for hookworm disease in humans. Necator americanus and
Ancylostoma duodenale have similar life cycles and
similar methods of causing illness. The adult worm
of both Necator americanus and Ancylostoma duodenale is about 10 mm long, pinkish-white in color, and
curved into an S-shape or double hook.
Both types of hookworm have similar life cycles.
The females produce about 10,000–20,000 eggs per
day. These eggs are passed out of the host’s body in
feces. The eggs enter the soil, where they incubate.
After about 48 hours, the immature larval form hatches
out of the eggs. These larvae take about six weeks to
develop into the mature larval form that is capable of
causing human infection. If exposed to human skin at
this point (usually bare feet walking in the dirt or bare
hands digging in the dirt), the larvae will bore through
the skin and ride through the lymph circulation to the
right side of the heart. The larvae are then pumped into
1843

Hookworm disease

PERIODICALS

KEY TERMS

Hookworm disease

KEY TERMS
Alveoli—The small air sacs clustered at the ends
of the bronchioles, in the lungs in which oxygencarbon dioxide exchange takes place.
Anemia—Any condition where the oxygen-carrying
capacity of the red blood cells is reduced; symptoms often include fatigue.
Host—The organism (like a human) in which
another infecting organism (like a worm) is living.
Larva—An immature form of an organism, occurring early in that organism’s development.

A micrograph image of the head of the hookworm
Ancylostoma spp. (Photo Researchers, Inc. Reproduced by
permission.)

the lungs. There they bore into the tiny air sacs (alveoli)
of the lungs. Their presence within the lungs usually
causes enough irritation to produce coughing. The
larvae are coughed up into the throat and mouth, and
are then swallowed and passed into the small intestine.
It is within the intestine that they develop into the adult
worm, producing illness in their human host.
Ancylostoma duodenale is found primarily in
the Mediterranean, the Middle East, and throughout
Asia. Necator americanus is common in tropical areas
including Asia, parts of the Americas, and throughout
Africa. Research suggests that at least 25% of all
people in the world have hookworm disease. In the
United States, 700,000 people are believed to be
infected with hookworms at any given time.

Causes and symptoms
Hookworms cause trouble for their human host
when the worms attach their mouths to the lining of
the small intestine and suck the person’s blood.
An itchy, slightly raised rash called ‘‘ground itch’’
may appear around the area where the larvae first
bored through the skin. The skin in this area may
become red and swollen. This lasts for several days
and commonly occurs between the toes.
When the larvae are in the lungs, the patient may
have a fever, cough, and some wheezing. Some people,
however, have none of these symptoms.
1844

Once established within the intestine, the adult
worms can cause abdominal pain, decreased appetite,
diarrhea, and weight loss. Most importantly, the
worms suck between 0.03–0.2 ml of blood per day.
When a worm moves from one area of the intestine
to another, it detaches its mouth from the intestinal
lining, leaving an irritated area that may continue to
bleed for some time. This results in even further blood
loss. A single adult worm can live for up to 14 years in
a patient’s intestine. Over time, the patient’s blood loss
may be very significant. Anemia is the most serious
complication of hookworm disease, progressing over
months or years. Children are particularly harmed
by such anemia, and can suffer from heart problems,
mental retardation, slowed growth, and delayed
sexual development. In infants, hookworm disease
can be deadly.

Diagnosis
Diagnosis of hookworm disease involves collecting
a stool sample for examination under a microscope.
Hookworm eggs have a characteristic appearance.
Counting the eggs in a specific amount of feces allows
the healthcare provider to estimate the severity of the
infection.

Treatment
Minor infections are often left untreated, especially in areas where hookworm is very common.
If treatment is required, the doctor will prescribe a
three-day dose of medication. One to two weeks
later, another stool sample will be taken to see if the
infection is still present.
Anemia is treated with iron supplements. In severe
cases, blood transfusion may be necessary. Two
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Estrone. Estrone is the form of estrogen present in
women after menopause. It is available as tablets
under the brand name Ogen. The most commonly
prescribed estrogen in the United States, Premarin, is
a so-called conjugated estrogen that is a mixture of
estrone and other estrogens.



Estradiol. This is the form of estrogen naturally present in perimenopausal women. It is available as
tablets (Estrace), skin patches (Estraderm), or vaginal creams (Estrace).



Estriol. Estriol is a weaker form of estrogen produced by the breakdown of other forms of estrogen
in the body. This is the form of estrogen most commonly given in Europe, under the brand name
Estriol. It is the only form that is thought not to
cause cancer.

Prognosis
The prognosis for patients with hookworm disease is generally good. However, reinfection rates are
extremely high in countries with poor sanitation.

Prevention
Prevention of hookworm disease involves improving sanitation and avoiding contact with soil in areas
with high rates of hookworm infection. Children
should be required to wear shoes when playing outside
in such areas, and people who are gardening should
wear gloves.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Hormone replacement
therapy
Definition
Hormone replacement therapy (HRT) is the use
of synthetic or natural female hormones to make
up for the decline or lack of natural hormones
produced in a woman’s body. HRT is sometimes
referred to as estrogen replacement therapy (ERT),
because the first medications that were used in the
1960s for female hormone replacement were estrogen compounds.
Estrogens
In order to understand how HRT works and the
controversies surrounding it, women should know
that there are different types of estrogen medications
commonly prescribed in the United States and
Europe. These drugs are given in a variety of prescription strengths and methods of administration. There
are at present three estrogen compounds used in
Western countries. Only the first two are readily available in the United States.
GALE ENCYCLOPEDIA OF MEDICINE

In addition to pills taken by mouth, skin patches,
and vaginal creams, estrogen preparations can be
given by injection or by pellets implanted under the
skin. Estrogen implants, however, are used less and
less frequently.
Progestins
Most HRT programs include progestin treatment
with estrogen compounds. Progestins—sometimes
called progestogens—are synthetic forms of progesterone that are given to reduce the possibility that estrogen by itself will cause cancer of the uterus. Progestins
are commonly prescribed under the brand names
Provera and Depo-Provera. Other common brand
names are Norlutate, Norlutin, and Aygestin.
Estrogen/testosterone combinations
Women’s ovaries secrete small amounts of a male
sex hormone (testosterone) throughout their lives.
Women who have had both ovaries removed by surgery are sometimes given testosterone along with
estrogen as part of HRT. Combinations of these hormones are available as tablets under the brand name
Estratest or as vaginal creams. Women who cannot
take estrogens can use 1% testosterone cream alone
for problems with vaginal soreness.
Estrogen/tranquilizer combinations
There are several medications that combine estrogen with a tranquilizer like chlordiazepoxide (sold
under the trade name Menrium) or meprobamate
(sold under the trade name PMB). Many doctors
warn against these combination drugs because the
tranquilizers can be habit-forming.
1845

Hormone replacement therapy

medications, pyrantel pamoate and mebendazole, are
frequently used with good results.

Hormone replacement therapy

Purpose
Hormone replacement therapy has been prescribed
for two primary purposes: preventive treatment against
osteoporosis and heart disease; and relief of physical
symptoms associated with menopause.
Menopausal symptoms
Women in midlife enter a stage of development
called menopause, when their menstrual periods
become irregular and finally stop. The early phase
of this transition is called the perimenopause. In
the United States, the average age at menopause is
presently 50 or 51, but some women begin menopause as early as 40 and others as late as 55. It can
take as long as 10 years for a woman to complete
the process. Women who have had their ovaries
removed surgically are said to have undergone surgical menopause.
Doctors have not always agreed on definitions of
menopause. Some use age as the baseline. Others define
menopause as the point when a woman has had no
menstrual periods for a full calendar year. Still others
define menopause as the end of ovulation. It is not
always clear, however, when a woman has had her
last period or when she has stopped ovulating. In
addition, women who take oral contraceptives can
have breakthrough bleeding long after they have
stopped ovulating. As a result, some doctors now measure the level of follicle-stimulating hormone (FSH) in
a woman’s blood to estimate whether the woman has
entered menopause. During perimenopause, the FSH
levels in a woman’s blood rise as her body attempts
to stimulate the release of ripe ova. An FSH level over
40 is considered an indicator of menopause.
During the menopausal transition, the levels of
estrogen in the woman’s body drop. The lowered
estrogen level is responsible for a group of symptoms
that include hot flashes (or flushes), weight gain,
changes in skin texture, mood swings, heart palpitations, sleep disturbances, a need to urinate more
frequently, and loss of sexual desire. The estrogen
that is given in HRT has been shown to eliminate hot
flashes, night sweats, lack of vaginal lubrication, and
urinary tract problems. HRT will not prevent weight
gain or wrinkles. It also does not cure depression in
most women.
Preventive care
HRT has been recommended by some doctors
to protect women against two serious midlife health
problems, including osteoporosis and heart disease.
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While clinical trials have continued to demonstrate
HRT’s effectiveness in preventing osteoporosis,
women must weigh the risk of the therapy with the
benefits. The trials also showed that HRT actually
increased rather than decreased risk of heart disease.
OSTEOPOROSIS. Osteoporosis is a disorder in
which the bones become more brittle and more easily
fractured. It is a particular problem for postmenopausal women because the lower levels of estrogen
in the blood lead to weakening of the bone. About
25% of Caucasian women will develop severe osteoporosis; Asian women have a slightly lower risk
level; Latino and African American women are
least at risk.

In addition to race, there are other factors that
put some women at higher risk of developing osteoporosis. Women in any of the following groups should
take bone loss into account when considering HRT:


family history of osteoporosis



menopause before age 40



kidney disease and dialysis



thin body build or being underweight



history of colitis, Crohn’s disease, or chronic diarrhea



thyroid medications



childlessness



chronic use of antacids



lack of exercise



poor food choices, including high salt intake, lack of
vitamin D, high caffeine consumption, and low calcium intake



smoking and alcohol abuse



cortisone therapy

HEART DISEASE. Heart disease is a major health
concern of women in midlife. It is the leading cause
of death in women over 60. The primary disorders of
the circulatory system in postmenopausal women are
stroke, hypertension, and coronary artery disease.
While doctors once believed that HRT helped
decrease heart disease and stroke among postmenopausal women, a major clinical trial discovered the
opposite to be true. In 2002, the Women’s Health
Initiative (WHI) stopped giving HRT to the women
enrolled in the study because of adverse effects.
Among these effects was a 29% increase in coronary
heart disease and 41% increase in stroke in postmenopausal women taking HRT.

Other major factors that are known to increase the
risk of heart disease include:
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Hormone replacement therapy

Estrogen replacement patch

Protective film
Hormone layer
Control membrane
Adhesive layer

Estrogen replacement patches adhere to a patient’s skin and slowly administer estrogen to the body. (Illustration by Argosy Inc.)



history of smoking



being overweight



high-fat diets



alcohol abuse



family history of heart disease



high blood pressure



high blood cholesterol levels



diabetes.

Less important risk factors include being African
American, having a sedentary lifestyle, undergoing
menopause before age 45, and having high levels of
family- or job-related stress.

WHI also found that combined estrogen/progesterone increased the risk of probable dementia in
women age 65 and older. Physicians and women
were advised not to panic about HRT, however.
Short-term use of the therapy may not produce
these risks. Women have been advised to meet with
their physicians and weigh the benefits against the
risks on an individual basis.
Certain groups of women should not use HRT.
They include women with:


breast cancer



cancer of the uterus



heart disease



abnormal vaginal bleeding that has not been
diagnosed



high blood pressure that rises when HRT is used



liver disease



gallstones or diseases of the gallbladder

Precautions
Medical conditions
The findings of the WHI presented new problems for the women relying on hormones to ease
their transition to menopause and postmenopausal
years and for doctors prescribing HRT. The combination of estrogen and progesterone also was found
to increase risk of invasive breast cancer by 26%,
which was the reason researchers halted the study.
In addition, while some clinicians have thought
that HRT helped delay dementia (a disorder of the
mind that affects memory and perception), the
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Drug interactions
HRT can interact with other prescription medications that a woman may be taking. Women who are
taking corticosteroids, drugs to slow the clotting of
blood (anticoagulants), and rifampin should ask
their doctor about possible interactions.
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Hormone replacement therapy

Combining estrogens with certain other medicines
can cause liver damage. Among the drugs that may
cause liver damage when taken with estrogens are:


acetaminophen (Tylenol), when used in high doses
over long periods



anabolic steroids such as nandrolone (Anabolin) or
oxymetholone (Anadrol)



medicine for infections



antiseizure medicines such as divalproex (Depakote),
valproic acid (Depakene), or phenytoin (Dilantin)



antianxiety drugs, including chlorpromazine
(Thorazine), prochlorperazine (Compazine), and
thioridazine (Mellaril).

In addition, estrogens may interfere with the
effects of bromocriptine (Parlodel), used to treat
Parkinson’s disease and other conditions; they may
also increase the chance of toxic side effects when
taken with cyclosporine (Sandimmune), a drug that
helps prevent organ transplant rejection.

Description
HRT medications come in several different forms,
including tablets, stick-on patches, injections, and
creams that are worn inside the vagina. The form
prescribed depends on the purpose of the hormone
replacement therapy. Women who want relief from
vaginal dryness, for example, would be given a cream
or vaginal ring. Women using HRT to relieve hot
flashes or to prevent osteoporosis and heart disease
often prefer oral medications or patches. All HRT
medications used in the United States are available
only with a doctor’s prescription.
HRT treatment regimens
One of the complications of HRT is the number of
treatment options, including combinations of types of
estrogen; dosage levels; forms of administration; and
whether or not progestins are used with the estrogen to
offset the risk of uterine cancer. This variety, however,
means that a woman who wants to use HRT while
minimizing side effects can try different forms of medication or dosage schedules when she consults her doctor.
It is vital, however, for women to follow their doctor’s
directions exactly and not change dosages themselves.
At present, women who are taking a combination
of estrogens and progestins are placed on one of three
dosage schedules:


Estrogen pills taken daily from the first through the
25th day of each month, with a progestin pill taken
daily during the last 10–14 days of the cycle. Both

1848

drugs are then stopped for the next five to six days to
allow the uterus to shed its lining.


Estrogen pills taken on a daily basis with low-dose
progestin pills, also on a daily basis. Both medications are taken continuously with no days off.



Estrogen pills and low-dose progestins taken on a
daily basis for five days each week, with both medications stopped on the last two days of each week.

TIMING AND LENGTH OF TREATMENT. One of the
disagreements about HRT concerns the best time to
begin using it. Some doctors think that women should
begin using HRT while they are still in perimenopause.
Others think that there is no harm in a woman’s waiting to decide. Either way, the question of timing means
that a woman should keep track of changes in her
periods and other signs of perimenopause so that her
doctor can evaluate her readiness for HRT.

The other question of timing concerns length of
treatment. Some women use HRT only as long as they
need it to relieve the symptoms of menopause. Others
regard it as a lifetime commitment because of concerns
about osteoporosis. One study found that the average
length of time that women stay on HRT is 23 months.
Information from the WHI released in 2002 and 2003
would indicate that long-term HRT use produced too
many risks for the expected benefits.
UNWANTED SIDE EFFECTS. In addition to the identified health risks mentioned above, much of the disagreement about unwanted side effects from HRT
concerns the role of progestins in the estrogen/progestin combinations that are commonly prescribed.
Many women who find that estrogen relieves hot
flashes and other symptoms of menopause have the
opposite experience with progestin. Progestin frequently causes moodiness, depression, sore breasts,
weight gain, and severe headaches.

Other treatment approaches
Women who are uncertain about HRT, or who
should not take estrogens, should know about other
treatment options, such as natural progesterone.
Progestins, which are synthetic hormones, were developed because natural progesterone cannot be absorbed
in the body when taken in pill form. A new technique
called micronization has made it possible for women to
take natural progesterone by mouth. Many women
prefer this form of hormone because it lacks the side
effects of the synthetic progestins even though it is
somewhat more expensive. The most common form
of natural progesterone is called Prometrium. which is
available by prescription only. Another form of natural
progesterone consists of the hormone suspended in
GALE ENCYCLOPEDIA OF MEDICINE

Alternative therapies also are available. Many
mainstream as well as alternative practitioners recommend changes in diet and nutrition as helpful during
menopause. Women who limit their intake of fats and
salts, increase their use of fresh fruits and vegetables,
quit smoking, and drink only in moderation often find
that these dietary changes help them feel better.
Naturopaths typically recommend vitamin and mineral
supplements for general well-being as well as for relief
from hot flashes and leg cramps. In addition, herbal
teas and tonics are helpful to some women in treating
water retention, insomnia, constipation, or moodiness.
Women who find menopause emotionally stressful because of negative social attitudes toward older
women are often helped by meditation, biofeedback,
therapeutic massage, and other relaxation techniques.
Yoga and tai chi provide physical exercise as well as
stress reduction. Exercise is an important safeguard
against osteoporosis.

Preparation
Women who are considering HRT should visit
their doctor for a series of tests to make sure that
they do not have any serious health disorders. They
should have a Pap smear and breast examination to
rule out cancer. They also should have a urinalysis, a
bone density test, and blood tests to measure their red
blood cell level, blood sugar level, cholesterol level,
and liver and thyroid function.
In addition to these tests, most doctors will also
give a progesterone challenge test. It consists of doses of
progesterone given over a 10-day period to see if the
woman is still producing her own estrogen. If she bleeds
at the end of the test, she is still producing estrogen.

Aftercare
Aftercare is a very important part of HRT.
Women who are taking HRT will need to see their
doctor more frequently. At a minimum, they should
be checked twice a year with a blood pressure test and
breast examination. They should have a complete physical on a yearly basis. Any abnormal bleeding must be
reported to the doctor as soon as it occurs. The doctor
will need to order a tissue biopsy or dilation and curettage (D & C) in order to rule out cancer of the uterus.
Women who are taking HRT and decide to stop
should taper their dosage over a period of several
months rather than discontinuing abruptly. A gradual
reduction minimizes the possibility of hot flashes and
other side effects.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Dilation and curettage (D & C)—A surgical procedure in which the patient’s cervix is widened
(dilated) and the endometrium is scraped with a
scoop-shaped instrument (curette).
Estrogen—The primary sex hormone that controls
normal sexual development in females. During the
menstrual cycle, estrogen helps prepare the body
for possible pregnancy.
Follicle-stimulating hormone (FSH)—A hormone
produced by the pituitary gland that stimulates the
follicles in the ovaries to swell and release ripe ova.
Doctors sometimes use its levels in a woman’s
blood to evaluate whether she is in menopause.
Hormone—A substance secreted by an endocrine
gland that is carried by blood or other body fluids to
its target tissues or organs.
Hot flash—A warm or hot sensation on the face,
neck and upper body, sometimes accompanied by
flushing and sweating. Some women refer to hot
flashes as hot flushes.
Osteoporosis—A bone disorder in which the bones
become brittle, porous, and easily broken. It is a
major health concern for postmenopausal women.
Ovary—The female sex gland that produces eggs
and female reproductive hormones.
Ovulation—The cyclical process of egg maturation
and release from the ovary.
Progesterone—A female hormone produced by the
ovary. It functions to prepare the lining of the uterus
to receive a fertilized ovum.
Progesterone challenge test—A test that is given to
see if a woman is still secreting estrogen. It consists
of doses of progesterone given over a 10-day period.
Progestin—Synthetic progesterone available as an
oral medication.
Testosterone—A male sex hormone that is sometimes given as part of HRT to women whose ovaries
have been removed. Testosterone helps with problems of sexual desire.
Uterus—The hollow organ in women in which
fertilized eggs develop during pregnancy. The
uterus is sometimes called the womb.

Risks
The short-term risks associated with HRT include
a range of physical side effects. Common side effects
include fluid retention, bloating, weight gain, sore
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Hormone replacement therapy

vitamin E oil. It is absorbed through the skin and is
available without a prescription.

Hospital-acquired infections

breasts, leg cramps, vaginal discharges, migraine headaches, hair loss, nausea and vomiting, acne, depression,
shortness of breath, and dizziness. Potentially serious
side effects include tissue growths in the uterus
(fibroids), gallstones, thrombophlebitis, hypoglycemia,
abnormal growth (hyperplasia) of uterine tissue, thyroid disorders, high blood pressure, and cancer.
Long-term risks should be discussed with a
woman’s physicians before considering hormone
replacement therapy. Identified risks for combined
(estrogen plus progestin) HRT use include increased
incidence of invasive breast cancer, stroke, heart disease, and pulmonary embolism.

Normal results
Normal results of HRT include relief of hot
flashes, night sweats, vaginal dryness, and urinary
symptoms associated with menopause.
Resources
BOOKS

Goldman, Lee, et al, editors. Cecil Textbook of Medicine.
21st ed. W. B. Saunders, 2000.
Goroll, Alan H. Primary Care Medicine. 4th ed. Lippincott
Williams & Wilkins, 2000.
PERIODICALS

Doering, Paul L. ‘‘Treatment of Menopause Post-WHI:
What Now?’’ Drug Topics April 21, 2003: 85.
Elliott, William T. ‘‘HRT, Estrogen, and Postmenopausal
Women: Year-old WHI Study Continues to Raise
Questions.’’ Critical Care Alert July 2003: 1.

Description
About 5–10% of patients admitted to hospitals in
the United States develop a nosocomial infection. The
Centers for Disease Control and Prevention (CDC)
estimate that more than two million patients develop
hospital-acquired infections in the United States
each year. About 90,000 of these patients die as a result
of their infections. Hospital-acquired infections usually
are related to a procedure or treatment used to diagnose
or treat the patient’s illness or injury. About 25% of
these infections can be prevented by healthcare workers
taking proper precautions when caring for patients.
Hospital-acquired infections can be caused by
bacteria, viruses, fungi, or parasites. These microorganisms may already be present in the patient’s body
or may come from the environment, contaminated
hospital equipment, health care workers, or other
patients. Depending on the causal agents involved, an
infection may start in any part of the body. A localized
infection is limited to a specific part of the body and has
local symptoms. For example, if a surgical wound in the
abdomen becomes infected, the area of the wound
becomes red, hot, and painful. A generalized infection
is one that enters the bloodstream and causes general
systemic symptoms such as fever, chills, low blood
pressure, or mental confusion.
Hospital-acquired infections may develop from
surgical procedures, catheters placed in the urinary
tract or blood vessels, or from material from the nose
or mouth that is inhaled into the lungs. The most
common types of hospital-acquired infections are
urinary tract infections (UTIs), pneumonia, and surgical wound infections.

OTHER

Menopausal Hormone Replacement Therapy. Fact sheet.
National Cancer Institute. <http://rex.nci.nih.gov>.

Laith Farid Gulli, M.D.
Teresa G. Odle

Hospital-acquired infections
Definition
A hospital-acquired infection is usually one that
first appears three days after a patient is admitted to a
hospital or other health care facility. Infections
acquired in a hospital are also called nosocomial
infections.
1850

Causes and symptoms
All hospitalized patients are susceptible to contracting a nosocomial infection. Some patients are at
greater risk than others—young children, the elderly,
and persons with compromised immune systems are
more likely to get an infection. Other risk factors for
getting a hospital-acquired infection are a long hospital stay, the use of indwelling catheters, failure of
healthcare workers to wash their hands, and overuse
of antibiotics.
Any type of invasive procedure can expose a
patient to the possibility of infection. Common causes
of hospital-acquired infections include:


urinary bladder catheterization



respiratory procedures



surgery and wounds



intravenous (IV) procedures
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The healthy urinary bladder is sterile, which
means it doesn’t have any bacteria or other microorganisms in it. There may be bacteria in or around
the urethra but they normally cannot enter the bladder. A catheter can pick up bacteria from the urethra
and allow them into the bladder, causing an infection
to start.
Bacteria from the intestinal tract are the most
common type to cause UTIs. Patients with poorly
functioning immune systems or who are taking antibiotics are also at risk for infection by a fungus called
Candida.
Pneumonia is the second most common type of
hospital-acquired infection. Bacteria and other microorganisms are easily brought into the throat by
respiratory procedures commonly done in the hospital. The microorganisms come from contaminated
equipment or the hands of health care workers. Some
of these procedures are respiratory intubation, suctioning of material from the throat and mouth, and
mechanical ventilation. The introduced microorganisms quickly colonize the throat area. This means that
they grow and form a colony, but do not yet cause an
infection. Once the throat is colonized, it is easy for a
patient to inhale the microorganisms into the lungs.
Patients who cannot cough or gag very well are
most likely to inhale colonized microorganisms into
their lungs. Some respiratory procedures can keep
patients from gagging or coughing. Patients who are
sedated or who lose consciousness may also be unable
to cough or gag. The inhaled microorganisms grow in
the lungs and cause an infection that can lead to
pneumonia.
Surgical procedures increase a patient’s risk of
getting an infection in the hospital. Surgery directly
invades the patient’s body, giving bacteria a way into
normally sterile parts of the body. An infection can be
acquired from contaminated surgical equipment or
from healthcare workers. Following surgery, the surgical wound can become infected. Other wounds from
trauma, burns, and ulcers may also become infected.
Many hospitalized patients need a steady supply
of medications or nutrients delivered to their
GALE ENCYCLOPEDIA OF MEDICINE

bloodstream. An intravenous (IV) catheter is placed
in a vein and the medication or other substance is
infused into the vein. Bacteria transmitted from the
surroundings, contaminated equipment, or healthcare
workers’ hands can invade the site where the catheter
is inserted. A local infection may develop in the skin
around the catheter. The bacteria also can enter the
blood through the vein and cause a generalized infection. The longer a catheter is in place, the greater the
risk of infection.
Other hospital procedures that put patients at risk
for nosocomial infection are gastrointestinal procedures, obstetric procedures, and kidney dialysis.
Fever is often the first sign of infection. Other
symptoms and signs of infection are rapid breathing,
mental confusion, low blood pressure, reduced urine
output, and a high white blood cell count.
Patients with a UTI may have pain when urinating
and blood in the urine. Symptoms of pneumonia may
include difficulty breathing and coughing. A localized
infection causes swelling, redness, and tenderness at
the site of infection.

Diagnosis
An infection is suspected any time a hospitalized
patient develops a fever that cannot be explained by a
known illness. Some patients, especially the elderly,
may not develop a fever. In these patients, the first
signs of infection may be rapid breathing or mental
confusion.
Diagnosis of a hospital-acquired infection is
based on:


symptoms and signs of infection



examination of wounds and catheter entry sites



review of procedures that might have led to infection



laboratory test results

A complete physical examination is conducted in
order to locate symptoms and signs of infection.
Wounds and the skin where catheters have been
placed are examined for redness, swelling, or the presence of pus or an abscess. The physician reviews the
patient’s record of procedures performed in the hospital to determine if any posed a risk for infection.
Laboratory tests are done to look for signs of
infection. A complete blood count can reveal if the
white blood cell count is high. White blood cells are
immune system cells that increase in numbers in
response to an infection. White blood cells or blood
may be present in the urine when there is a UTI.
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Hospital-acquired infections

Urinary tract infection (UTI) is the most common
type of hospital-acquired infection. Most hospitalacquired UTIs happen after urinary catheterization.
Catheterization is the placement of a catheter
through the urethra into the urinary bladder. This
procedure is done to empty urine from the bladder,
relieve pressure in the bladder, measure urine in the
bladder, put medicine into the bladder, or for other
medical reasons.

Hospital-acquired infections

Cultures of blood, urine, sputum, other body
fluids, or tissue are done to look for infectious microorganisms. If an infection is present, it is necessary
to identify the microorganism so the patient can be
treated with the correct medication. A sample of the
fluid or tissue is placed in a special medium that
bacteria will grow in. Other tests can also be done
on blood and body fluids to look for and identify
bacteria, fungi, viruses, or other microorganisms
responsible for an infection.
If a patient has symptoms suggestive of pneumonia, a chest x ray is done to look for infiltrates of
white blood cells and other inflammatory substances
in the lung tissue. Samples of sputum can be studied
with a microscope or cultured to look for bacteria
or fungi.

Treatment
Once the source of the infection is identified, the
patient is treated with antibiotics or other medication that kills the responsible microorganism. Many
different antibiotics are available that are effective
against different bacteria. Some common antibiotics
are penicillin, cephalosporins, tetracyclines, and erythromycin. More and more commonly, some types
of bacteria are becoming resistant to the standard
antibiotic treatments. When this happens, a different, more powerful antibiotic must be used. Two
strong antibiotics that have been effective against
resistant bacteria are vancomycin and imipenem,
although some bacteria are developing resistance
to these antibiotics as well.
Fungal infections are treated with antifungal
medications. Examples of these are amphotericin B,
nystatin, ketoconazole, itraconazole, and fluconazole.
A number of antiviral drugs have been developed
that slow the growth or reproduction of viruses.
Acyclovir, ganciclovir, foscarnet, and amantadine
are examples of antiviral medications.

Prognosis
Hospital-acquired infections are serious illnesses
that cause death in about 1% of cases. Rapid diagnosis
and identification of the responsible microorganism is
necessary, so treatment can be started as soon as
possible.

Prevention
Hospitals and other healthcare facilities have
developed extensive infection control programs to
1852

KEY TERMS
Abscess—A localized pocket of pus at a site of
infection.
Candida—A yeast-like fungal organism.
Catheter—A thin, hollow tube inserted into the
body at specific points in order to inject or withdraw fluids from the body.
Generalized infection—An infection that has
entered the bloodstream and has general systemic
symptoms such as fever, chills, and low blood
pressure.
Localized infection—An infection that is limited to
a specific part of the body and has local symptoms.
Nosocomial infection—An infection acquired in
the hospital.

prevent nosocomial infections. These programs
focus on identifying high risk procedures and other
possible sources of infection. High risk procedures
such as urinary catheterization should be performed
only when necessary and catheters should be left
in for as little time as possible. Medical instruments
and equipment must be properly sterilized to ensure
they are not contaminated. Frequent handwashing
by healthcare workers and visitors is necessary
to avoid passing infectious microorganisms to hospitalized patients. In 2003, the Joint Commission
on Accreditation of Healthcare Organizations
(JCAHO) announced it would make prevention
of nosocomial infections a major goal in 2004 and
the coming years. JCAHO, the body that inspects
hospitals for quality and accredits them accordingly, issued an alert stating that hospital-acquired
infections are seriously underreported. The problem has become more serious for hospitals to
address as many bacteria are becoming resistant
to antibiotics.
Antibiotics should be used only when necessary.
Use of antibiotics creates favorable conditions for
infection with the fungal organism Candida. Overuse
of antibiotics is also responsible for the development
of bacteria that are resistant to antibiotics.
Resources
PERIODICALS

Burke, John P. ‘‘Infection Control—A Problem for Patient
Safety.’’ The New England Journal of Medicine
February 13, 2003: 651–656.

GALE ENCYCLOPEDIA OF MEDICINE

Toni Rizzo
Teresa G. Odle

Hot-spot imaging see Technetium heart scan
HRT see Hormone replacement therapy
HTLV-1 associated myelopathy see Tropical
spastic paraparesis
HTLV-1 infection see Tropical spastic
paraparesis

Human-potential movement
Definition

Purpose
The purpose of humanistic therapy is to allow a
person to make full use of his or her personal capacities leading to self-actualization. Self-actualization
requires the integration of all the components of
one’s unique personality. These elements or components of personality include the physical, emotional,
intellectual, behavioral, and spiritual. The marks of a
self-actualized person are maturity, self-awareness,
and authenticity. Humanistic therapists think that
most people—not only those with obvious problems—
can benefit from opportunities for self-development.
Humanistic therapy uses both individual and group
approaches.

Precautions
Psychotic patients, substance abusers, and persons with severe personality disorders or disorders of
impulse control may not be appropriate for treatment
with humanistic methods.

Description

The human-potential movement is a term used for
humanistic psychotherapies that first became popular
in the 1960s and early 1970s. The movement emphasized the development of individuals through such
techniques as encounter groups, sensitivity training,
and primal therapy. Although the human-potential
movement and humanistic therapy are sometimes
used as synonyms, in reality, humanistic therapy preceded the human-potential movement and provided
the movement’s theoretical base. Humanistic therapy
flourished in the 1940s and 1950s. Its theorists were
mostly psychologists rather than medical doctors.
They included Gordon Allport, Abraham Maslow,
Everett Shostrom, Carl Rogers, and Fritz Perls.

Humanistic approaches to individual treatment
usually follow the same format as other forms of
outpatient counseling. Therapists may be medical
doctors, nurses, psychologists, social workers, or
clergy. Humanistic group treatment formats are flexible, and a wide range of treatment methods are
used, ranging from encounter groups and therapy
groups to assertiveness training and consciousnessraising groups. In addition, the humanistic tradition
has fostered the publication of self-help books for
people interested in psychological self-improvement.

The human-potential movement and humanistic
therapy is distinguished by the following emphases:

The chief risks include the reinforcement of selfcentered tendencies in some patients and the dangers
resulting from encounter groups led by persons without adequate training. Poorly led encounter groups
can be traumatic to persons with low tolerance for
confrontation or ‘‘uncovering’’ of private issues.



A concern for what is uniquely human rather than
what humans share with other animals.



A focus on each person’s open-ended growth rather
than reshaping individuals to fit society’s demands.



An interest in the here-and-now rather than in a
person’s childhood history or supposed unconscious
conflicts.



A holistic approach concerned with all levels of
human being and functioning—not just the intellectual—including creative and spiritual functioning.



A focus on psychological health rather than
disturbance.

GALE ENCYCLOPEDIA OF MEDICINE

Risks

Normal results
The anticipated outcome of humanistic therapy is
a greater degree of personal wholeness, self-acceptance,
and exploration of one’s potential. In group treatment,
participants are expected to grow in interpersonal
empathy and relationship skills. However, there have
been few controlled studies to determine the reasonableness of these expectations.
1853

Human-potential movement

‘‘Hospital-Acquired Infections are Being Underreported.’’
RN March 2003: 16.
‘‘Nosocomial Infection (From the Editor).’’ Health Care
Food & Nutrition Focus June 2003: 2.

Human bite infections

Causes and symptoms

KEY TERMS
Encounter group—A form of humanistic therapy in
which participants meet with a trained leader to
increase self-awareness and social skills through
emotional sharing and confrontation.
Humanistic therapy—An approach to psychotherapy that emphasizes human uniqueness, positive
qualities, and individual potential. It is sometimes used
as a synonym for the human potential movement.
Primal therapy—A form of humanistic therapy that
originated in the 1970s. Participants were encouraged to relive painful events and release feelings
through screaming or crying rather than analysis.
Sensitivity training—A form of humanistic group
therapy that began in the 1950s. Members participated in unstructured discussions in order to
improve understanding of themselves and others.

Resources
BOOKS

Severin, Frank T. ‘‘Humanistic Psychology.’’ In The
Encyclopedia of Psychiatry, Psychology, and
Psychoanalysis, edited by Benjamin B. Wolman.
New York: Henry Holt and Co., 1996.

Rebecca J. Frey, PhD

Human bite infections
Definition
Human bite infections are potentially serious
infections caused by rapid growth of bacteria in broken skin.

Description
Bites—animal and human—are responsible for
about 1% of visits to emergency rooms. Bite injuries
are more common during the summer months.
Closed-fist injury
In adults, the most common form of human bite is
the closed-fist injury, sometimes called the ‘‘fight
bite.’’ These injuries result from the breaking of the
skin over the knuckle joint when a person’s fist strikes
someone’s teeth during a fight.
1854

In children, bite infections result either from accidents during play or from fighting. Most infected bites
in adults result from fighting.
The infection itself can be caused by a number of
bacteria that live in the human mouth. These include
streptococci, staphylococci, anaerobic organisms,
and Eikenella corrodens. Infections that begin less than
24 hours after the injury are usually produced by a
mixture of organisms and can cause a necrotizing infection (causing the death of a specific area of tissue), in
which tissue is rapidly destroyed. If a bite is infected, the
skin will be sore, red, swollen, and warm to the touch.

Diagnosis
In most cases the diagnosis is made by an emergency
room physician on the basis of the patient’s history.
Because the human mouth contains a variety of
bacteria, the physician will order a laboratory culture
to choose the most effective antibiotic.

Treatment
Treatment involves surgical attention as well as
medications. Because bites cause puncturing and tearing of skin rather than clean-edged cuts, they must be
carefully cleansed. The doctor will wash the wound
with water under high pressure and debride it.
Debridement is the removal of dead tissue and foreign
objects from a wound to prevent infection. If the bite
is a closed-fist injury, the doctor will look for torn
tendons or damage to the spaces between the joints.
Examination includes x rays to check for bone fractures or foreign objects in the wound.
Doctors do not usually suture a bite wound
because the connective tissues and other structures
in the hand form many small closed spaces that make
it easy for infection to spread. Emergency room doctors often consult surgical specialists if a patient has a
deep closed-fist injury or one that appears already
infected.
The doctor will make sure that the patient is
immunized against tetanus, which is routine procedure
for any open wound. A study released in June 2004
showed that routine use of antibiotics for human bites
may not be necessary, as physicians try to minimize
overuse of antibiotics. Superficial wounds in low-risk
areas may no longer need antibiotic treatment, but
more serious human bites to high-risk areas such as
the hands should be treated with antibiotics to prevent
serious infection. Patients with closed-fist injuries
GALE ENCYCLOPEDIA OF MEDICINE

Closed-fist injury—A hand wound caused when
the skin of the fist is torn open by contact with teeth.
Debridement—The surgical removal of dead tissue
and/or foreign bodies from a wound or cut.
‘‘Fight bite’’—Another name for closed-fist injury.
Necrotizing—Causing the death of a specific area
of tissue. Human bites frequently cause necrotizing
infections.

may need inpatient treatment in addition to an intravenous antibiotic.

Prognosis
The prognosis depends on the location of the bite
and whether it was caused by a child or an adult. Bites
caused by children rarely become infected because
they are usually shallow. Between 15–30% of bites
caused by adults become infected, with a higher rate
for closed-fist injuries.

Prevention
Prevention of human bite infections depends
upon prompt treatment of any bite caused by a
human being, particularly a closed-fist injury.
Resources
PERIODICALS

‘‘Do All Human Bite Wounds Need Antibiotics?’’
Emergency Medicine Alert June 2004: 3.

Rebecca J. Frey, PhD
Teresa G. Odle

Human chorionic gonadotropin see
Infertility drugs

To determine whether or not a woman is
pregnant.

Description
Shortly after a woman’s egg is fertilized by her
male partner’s sperm and is implanted in the lining
or the womb (uterus), a placenta begins to form. This
organ will help nourish the developing new life. The
placenta produces hCG, whose presence, along
with other hormones, helps maintain the early stages
of pregnancy. Because hCG is produced only by placental tissue and the hormone can be found in the
blood or urine of a pregnant woman, it has become a
convenient chemical test of pregnancy.
After implantation, the level of detectable hCG
rises very rapidly, approximately doubling in quantity
every two days until a peak is reached between the
sixth and eighth week. Over the next ten or more
weeks, the quantity of hCG slowly decreases. After
this point, a much lower level is sustained for the
duration of the pregnancy. Detectable levels of this
hormone may even persist for a month or two after
delivery.
Blood tests for hCG are the most sensitive
and can detect a pregnancy earlier than urine tests.
Blood tests for hCG can also distinguish normal
pregnancies from impending miscarriages or pregnancies that occur outside of the uterus (ectopic
pregnancies).
If a woman misses her menstrual period and wants
to know if she may be pregnant, she can purchase one
of many home pregnancy test kits that are currently
available. Although each of these products may look
slightly different and provide a different set of directions for use, each one detects the presence of hCG.
This indicator contains chemical components called
antibodies that are sensitive to a certain quantity of
this hormone.

Precautions

Human chorionic
gonadotropin pregnancy test
Definition
The most common test of pregnancy involves the
detection of a hormone known as human chorionic
gonadotropin (hCG) in a sample of blood or urine.
GALE ENCYCLOPEDIA OF MEDICINE

Although home pregnancy tests may be advertised as having an accuracy of 97% or better, studies
indicate that, in practice, pregnancy tests performed
in the home may incorrectly indicate that a woman
is not pregnant (a false positive result) between
25–50% of the time. Studies also indicate that the
false negative results usually result from failing to
follow the package directions or testing too soon
after a missed menstrual period. Waiting a few days
1855

Human chorionic gonadotropin pregnancy test

Purpose

KEY TERMS

Human chorionic gonadotropin pregnancy test

KEY TERMS
Ectopic pregnancy—A pregnancy that develops outside of the mother’s uterus. Ectopic pregnancies
often cause severe pain in the lower abdomen and
are potentially life-threatening because of the massive blood loss that may occur as the developing
embryo/fetus ruptures and damages the tissues in
which it has implanted.
Embryo—In humans, the developing individual from
the time of implantation to about the end of the second month after conception. From the third month to
the point of delivery, the individual is called a fetus.
Hormone—A chemical produced by a specific
organ or tissue of the body that is released into the
bloodstream in order to exert an effect in another
part of the body.
Human chorionic gonadotropin (hCG)—A hormone
produced by the placenta of a developing pregnancy.
Hydatidiform mole—A rare, generally benign grapelike mass that grows in the uterus from the remains of
an abnormally developed embryo and surrounding
tissue. In extremely rare cases, the mole develops
into a choriocarcinoma, a malignant tumor whose
cells can invade the wall of the uterus.
Implantation—The attachment of the fertilized egg
or embryo to the wall of the uterus.

after the missed period was expected can increase the
accuracy of the test. Blood and urine tests performed
by a laboratory are from 97–100% accurate in detecting pregnancy.

Menstrual cycle—A hormonally regulated series of
monthly events that occur during the reproductive
years of the human female to ensure that the proper
internal environment exists for fertilization, implantation, and development of a baby. Each month, a
mature egg is released from the follicle of an ovary.
If an egg is released, fertilized, and implanted, the
lining of the uterus continues to build. If fertilization
and/or implantation does not occur, the egg and all
of the excess uterine lining are shed from the body
during menstruation.
Miscarriage—Loss of the embryo or fetus and other
products of pregnancy before the middle of the second trimester. Often, early in a pregnancy, if the
condition of the baby and/or the mother’s uterus is
not compatible with sustaining life, the pregnancy
stops, and the contents of the uterus are expelled. For
this reason, miscarriage is also referred to as spontaneous abortion.
Placenta—The organ that unites the developing new
life (first called an embryo and later a fetus) to the
mother’s uterus. The placenta produces hCG, among
other hormones, to help maintain the pregnancy.
After delivery, the placenta, known at this point as
afterbirth, is expelled.

Aftercare
No special care is required after a urine test
for hCG. Women who feel faint or who continue to
bleed after a blood test should be observed until the
condition goes away.

Preparation
Generally, no preparation is required for a pregnancy test given in a doctor’s office.
Home pregnancy test kits can be divided into
two basic types. One type involves the use of a wandlike device that a woman must place into her urine
stream for a brief period of time. The other type of kit
involves the use of a cup, a dropper, and a wand or
stick with a small well. The cup is used to collect the
urine, and the dropper is used to transfer a specific
number of drops into the well. Results are displayed
by a color change. It’s important to follow the package
directions very carefully (the techniques vary from
brand to brand) and to read the results in the time
specified.
1856

Risks
Tests for hCG levels pose no direct risk to a
woman’s health. The main risk with a home pregnancy
test is a false negative result, which may be lessened by
following the manufacturer’s instructions carefully
and waiting at least several days after the expected
menstrual period to test. A false negative result can
cause a delay in seeking prenatal care, which can pose
a risk to both the woman and the baby.

Abnormal results
In most cases, a positive result is an indication
of pregnancy. However, false positive results may
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
A woman should notify her physician immediately if her home pregnancy test is positive.
Pregnancy can then be confirmed with hCG urine or
blood tests taken in the doctor’s office and evaluated
by laboratory personnel. If performed accurately,
home pregnancy tests have been found to be highly
reliable. However, the versions of these tests performed by qualified laboratory technologists are
considered to be definitive. Often, such a test will
produce positive results before a woman experiences
symptoms or before a doctor’s exam reveals signs of
pregnancy.
Resources
PERIODICALS

Bastian, L. A., et al. ‘‘Is This Patient Pregnant?’’ The Journal
of the American Medical Association 278, no. 7: 586-591.
Peredy, T. R., and R. D. Powers. ‘‘Bedside Diagnostic
Testing of Body Fluids.’’ American Journal of
Emergency Medicine 15, no. 4: 404-405.

Betty Mishkin

Human herpes see Roseola

Human leukocyte antigen test
Definition
The human leukocyte antigen test, also known as
HLA, is a test that detects antigens (genetic markers)
on white blood cells. There are four types of human
leukocyte antigens: HLA-A, HLA-B, HLA-C, and
HLA-D.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
The HLA test is used to provide evidence of tissue
compatibility typing of tissue recipients and donors. It
is also an aid in genetic counseling and in paternity
testing.

Precautions
This test may have to be postponed if the patient
has recently undergone a transfusion.

Description
Human leukocyte antigen (leukocyte is the name
for white blood cell, while antigen refers to a genetic
marker) is a substance that is located on the surface of
white blood cells. This substance plays an important
role in the body’s immune response.
Because the HLA antigens are essential to
immunity, identification aids in determination of
the degree of tissue compatibility between transplant
recipients and donors. Testing is done to diminish
the likelihood of rejection after transplant, and to
avoid graft-versus-host disease (GVHD) following
major organ or bone marrow transplantation. It
should be noted that risk of GVHD exists even
when the donor and recipient share major antigens.
As an example, it was recently discovered that a
mismatch of HA-1 (a minor antigen) was a cause
of GVHD in bone marrow grafts from otherwise
HLA-identical donors.
HLA can aid in paternity exclusion testing, a
highly specialized area of forensic medicine. To
resolve cases of disputed paternity, a man who demonstrates a phenotype (two haplotypes: one from the
father and one from the mother) with no haplotype
or antigen pair identical to one of the child’s is
excluded as the father. Conversely, a man who has
one haplotype identical to one of the child’s may be
the father (the probability varies with the appearance
of that particular haplotype in the population).
Because of the issues involved, this type of testing is
referred to experts.
Certain HLA types have been linked to diseases, such as rheumatoid arthritis, multiple sclerosis, serum lupus erythematosus, and other
autoimmune disorders. By themselves, however,
none of the HLA types are considered definitive.
Because the clinical significance of many of the
marker antigens has not yet been well defined, definitive diagnosis of disease is obtained by the use of
more specific tests.
1857

Human leukocyte antigen test

also occur. If a pregnancy test is performed within a
month or two of a recent birth or miscarriage, it is
possible to test positive for pregnancy since hCG
may still be detected in a woman’s urine. Sometimes
positive pregnancy tests provide clues of an early
miscarriage that might have otherwise gone unrecognized because it occurred before or just after a
missed period. An ectopic pregnancy (one in which
an embryo implants outside the uterus), certain types
of masses (such as an ovarian tumor or a hydatidiform mole), and the use of some fertility drugs that
contain hCG are among other possibilities behind
false positive results.

Huntington disease

KEY TERMS
Autoimmune disorders—A disorder caused by a
reaction of an individual’s immune system against
the organs or tissues of the body. Autoimmune
processes can have different results: slow destruction of a particular type of cell or tissue, stimulation
of an organ into excessive growth, or interference
in function.
Haplotype—A set of alleles (an alternative form of a
gene that can occupy a particular place on a chromosome) of a group of closely linked genes which
are usually inherited as a unit.
Phenotype—1) The entire physical, biochemical,
and physiologic makeup of an individual, as
opposed to genotype. 2) The expression of a single
gene or gene pair.

B7, and B14. HLA-A3 is found in approximately 70%
of patients with hemochromatosis, but as is the case
with other HLA-associated disorders, the expense of
HLA typing favors use of other tests. In cases of
suspected hemochromatosis, for example, diagnosis
is better aided by two tests called transferrin saturation and serum ferritin.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Humanistic therapy see Gestalt therapy;
Human-potential movement
Humpback see Kyphosis
Hunchback see Kyphosis

Preparation
The HLA test requires a blood sample. There is no
need for the patient to be fasting (having nothing to eat
or drink) before the test.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or
feeling lightheaded after venipuncture, or hematoma
(blood accumulating under the puncture site).

Normal results
Identification of specific leukocyte antigens,
HLA-A, HLA-B, HLA-C and HLA-D.

Abnormal results
ncompatible groups between organ donors and
recipients may cause unsuccessful tissue transplantation.
Certain diseases have a strong association with
certain types of HLAs, which may aid in genetic counseling. For example, Hashimoto’s thyroiditis (an autoimmune disorder involving underproduction by the
thyroid gland) is associated with HLA-DR5, while
B8 and Dw3 are allied with Graves’ disease (another
autoimmune disorder, but with overproduction by the
thyroid gland). Hereditary hemochromatosis (too
much iron in the blood) is associated with HLA-A3,
1858

Hunter’s syndrome see
Mucopolysaccharidoses

Huntington disease
Definition
Huntington disease (HD) is a progressive neurodegenerative disease causing uncontrolled physical
movements and mental deterioration. The disease
was discovered by George Sumner Huntington
(1850–1916), an Ohio doctor who first described the
hereditary movement disorder in 1872.

Description
Huntington disease is also called Huntington
chorea or hereditary chorea. The word chorea comes
from the Greek word for ‘‘dance’’ and refers to the
involuntary movements of the patient’s feet, lower
arms, and face that develop as the disease progresses.
It is occasionally referred to as ‘‘Woody Guthrie’s
disease’’ for the American folk singer who died from
it. Huntington disease (HD) causes progressive loss of
cells in areas of the brain responsible for certain
aspects of movement control and mental abilities.
A person with HD gradually develops abnormal
movements and changes in cognition (thinking), behavior and personality.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Huntington disease is caused by a defect in the
HD gene (an inherited unit which contains a code for
a protein), which is located on the short arm of
chromosome 4. The gene codes for a protein called
huntingtin, whose function is not known as of early
2005. The nucleotide codes (building blocks of genes
arranged in a specific code which chemically forms
into proteins), contain CAG repeats (40 or more of
these repeat sequences). The extra building blocks
in the huntingtin gene cause the protein that is
made from it to contain an extra section as well. It is
currently thought that this extra protein section, or
portion, interacts with other proteins in brain cells
where it occurs, and that this interaction ultimately
leads to cell death.
The HD gene is a dominant gene, meaning that
only one copy of it is needed to develop the disease.
HD affects both males and females. The gene may be
inherited from either parent, who will also be affected
by the disease. A parent with the HD gene has a 50%
chance of passing it on to each offspring. The chances
of passing on the HD gene are not affected by the
results of previous pregnancies.
The symptoms of HD fall into three categories:
motor or movement symptoms; personality and behavioral changes; and cognitive decline. The severity and
rate of progression of each type of symptom can vary
from person to person.
Early motor symptoms include restlessness,
twitching and a desire to move about. Handwriting
may become less controlled, and coordination may
decline. Later symptoms include:


dystonia, or sustained abnormal postures, including
facial grimaces, a twisted neck, or an arched back



chorea, in which involuntary jerking, twisting or
writhing motions become pronounced



slowness of voluntary movements, inability to regulate the speed or force of movements, inability to
initiate movement and slowed reactions



difficulty speaking and swallowing due to involvement of the throat muscles

GALE ENCYCLOPEDIA OF MEDICINE



localized or generalized weakness and impaired balance ability



rigidity, especially in late-stage disease

Personality and behavioral changes include
depression, irritability, anxiety and apathy. The person with HD may become impulsive, aggressive or
socially withdrawn.
Cognitive changes include loss of ability to plan
and execute routine tasks, slowed thought, and
impaired or inappropriate judgment. Short-term memory loss usually occurs, although long-term memory
is usually not affected. The person with late-stage
HD usually retains knowledge of his environment
and recognizes family members or other loved ones,
despite severe cognitive decline.

Diagnosis
Diagnosis of HD begins with a detailed medical
history, and a thorough physical and neurological
examination. The family’s medical history is very
important. Magnetic resonance imaging (MRI) or
computed tomography scan (CT scan) imaging may
be performed to look for degeneration in the basal
ganglia and cortex, the brain regions most affected
in HD.
Physicians have recently developed a Uniform
Huntington’s Disease Rating Scale, or UHDRS, to
assess a patient’s symptoms and the speed of progression of the disease.
A genetic test is available for confirmation of the
clinical diagnosis. In this test, a small blood sample is
taken, and DNA from it is analyzed to determine the
CAG repeat number. A person with a repeat number
of 30 or below will not develop HD. A person with a
repeat number between 35 and 40 may not develop the
disease within their normal lifespan. A person with a
very high number of repeats (70 or above) is likely to
develop the juvenile-onset form. An important part of
genetic testing is extensive genetic counseling.
Prenatal testing is available. A person at risk for
HD (a child of an affected person) may obtain fetal
testing without determining whether she herself carries
the gene. This test, also called a linkage test, examines
the pattern of DNA near the gene in both parent and
fetus, but does not analyze for the triple nucleotide
repeat (CAG). If the DNA patterns do not match, the
fetus can be assumed not to have inherited the HD
gene, even if present in the parent. A pattern match
indicates the fetus probably has the same genetic
makeup of the at-risk parent.
1859

Huntington disease

The onset of symptoms of HD usually occurs
between the ages of 30 and 50; although in 10% of
cases, onset is in late childhood or early adolescence.
Approximately 30,000 people in the United States are
affected by HD, with another 150,000 at risk for developing this disorder. The frequency of HD is 4–7 cases
per 100,000 persons.

Huntington disease

Treatment
There is no cure for HD, nor any treatment that
can slow the rate of progression. Treatment is aimed
at reducing the disability caused by the motor impairments, and treating behavioral and emotional
symptoms.
Physical therapy is used to maintain strength and
compensate for lost strength and balance. Stretching
and range of motion exercises help minimize contracture, or muscle shortening, a result of weakness and
disuse. The physical therapist also advises on the use
of mobility aids such as walkers or wheelchairs.
Motor symptoms may be treated with drugs,
although some studies suggest that anti-chorea treatment rarely improves function. Chorea (movements
caused by abnormal muscle contractions) can be suppressed with drugs that deplete dopamine, an important brain chemical regulating movement. As HD
progresses, natural dopamine levels fall, leading to
loss of chorea and an increase in rigidity and movement slowness. Treatment with L-dopa (which resupplies dopamine) may be of some value. Frequent
reassessment of the effectiveness and appropriateness
of any drug therapy is necessary.
Occupational therapy is used to design compensatory strategies for lost abilities in the activities of
daily living, such as eating, dressing, and grooming.
The occupational therapist advises on modifications
to the home that improve safety, accessibility, and
comfort.
Difficulty swallowing may be lessened by preparation of softer foods, blending food in an electric
blender, and taking care to eat slowly and carefully.
Use of a straw for all liquids can help. The potential
for choking on food is a concern, especially late in the
disease progression. Caregivers should learn the use
of the Heimlich maneuver. In addition, passage of
food into the airways increases the risk for pneumonia.
A gastric feeding tube may be needed, if swallowing
becomes too difficult or dangerous.
Speech difficulties may be partially compensated
by using picture boards or other augmentative communication devices. Loss of cognitive ability affects
both speech production and understanding. A speechlanguage pathologist can work with the family to
develop simplified and more directed communication
strategies, including speaking slowly, using simple
words, and repeating sentences exactly.
Early behavioral changes, including depression
and anxiety, may respond to drug therapy.
Maintaining a calm, familiar, and secure environment
1860

is useful as the disease progresses. Support groups
for both patients and caregivers form an important
part of treatment.
Experimental transplant of fetal brain tissue has
been attempted in a few HD patients. Early results
show some promise, but further trials are needed to
establish the effectiveness of this treatment.
Tetrabenazine (Nitoman), a drug that has been
considered investigational in the United States,
appears to benefit some patients with HD by controlling the involuntary movements of chorea. It works
by lowering the levels of dopamine and other neurotransmitters in the brain. The Food and Drug
Administration (FDA) granted tetrabenazine fasttrack and orphan drug status in the United States as
of 2004. It is not yet manufactured in the United States
but can be obtained from the United Kingdom.
In 2004 the Food and Drug Administration (FDA)
also approved deep brain stimulation (DBS) as an
acceptable treatment for HD and other movement disorders. In DBS, the surgeon implants a battery-operated
medical device called a neurostimulator, which delivers
electrical impulses to the areas of the brain that govern
movement. In the case of Huntington’s patients, the
part of the brain that is targeted is a structure called
the globus pallidus. It is thought that DBS works by
increasing the flow of blood to this area. A group of
Canadian researchers reported in 2004 that some
patients with HD are better able to control their movements after DBS of the globus pallidus.
Psychotherapy is often recommended for individuals who know themselves to be at risk for the disease. Some persons want to know their risk status
while others prefer not to be tested. Psychotherapy
may be useful in helping at-risk persons decide about
testing as well as coping with the results of the test.

Prognosis
The person with Huntington disease may be able to
maintain a job for several years after diagnosis, despite
the increase in disability. Loss of cognitive functions
and increase in motor and behavioral symptoms eventually prevent the person with HD from continuing
employment. Ultimately, severe motor symptoms prevent mobility. Death usually occurs between 10 and 30
years after disease onset, typically as the result of pneumonia or a fall. Progressive weakness of respiratory and
swallowing muscles leads to increased risk of respiratory infection and choking, the most common causes of
death. Future research in this area is currently focusing
on nerve cell transplantation.
GALE ENCYCLOPEDIA OF MEDICINE

Basal ganglia—A structure at the base of the brain
composed of four groups of nerve cells, responsible
for body movements and coordination.
Chorea—Brief and purposeless involuntary movements of the lower arms, feet, and face.
Chromosome—The structures that carry genetic
information. Chromosomes are located within
every cell, and are responsible for directing the
development and functioning of all the cells in the
body. The normal number is 46 (23 pairs).
Cortex—The part of the brain responsible for
thought, memory, and sensory perception.
Dystonia—A movement disorder characterized by
sustained muscle contractions that result in writhing
or twisting movements and unsual body postures.
Globus pallidus—A pale-colored spherical structure within the basal ganglia. Deep brain stimulation of this area is helpful in controlling the chorea
of some patients with HD.
Huntingtin—A protein of unknown function
encoded by the HD gene. The repeated CAG
sequence in a defective HD gene causes the body
to produce an abnormal form of huntingtin. It is not
yet known why the abnormal form of huntingtin
affects only certain regions of the brain.
Orphan drug—A term for a drug that treats a rare
disease, defined by the Food and Drug
Administration (FDA) as one that affects fewer than
200,000 Americans. The FDA has an Office of
Orphan Products Development (OOPD), which
offers grants to researchers to develop these products.
Tetrabenazine—A drug given to control chorea
that appears to benefit HD patients.

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disorders of Movement.’’ Section 14, Chapter 179 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Montgomery, E. B., Jr. ‘‘Deep Brain Stimulation for
Hyperkinetic Disorders.’’ Neurosurgical Focus 17
(July 15, 2004): E1.
Moro, E., A. E. Lang, A. P. Strafella, et al. ‘‘Bilateral Globus
Pallidus Stimulation for Huntington’s Disease.’’ Annals
of Neurology 56 (August 2004): 290–294.
GALE ENCYCLOPEDIA OF MEDICINE

Revilla, Fredy J., MD, and Jaime Grutzendler, MD.
‘‘Huntington Disease.’’ eMedicine November 3, 2004.
<http://www.emedicine.com/NEURO/
topic81.htm>.
Richartz, E. R., and C. Frank. ‘‘A Psychodynamic
Approach in Counselling Vulnerable Persons for
Chorea Huntington—A Case Report.’’ [in German]
Psychiatrische Praxis 31 (July 2004): 255–258.
Seneca, S., D. Fagnart, K. Keymolen, et al. ‘‘Early-Onset
Huntington Disease: A Neuronal Degeneration
Syndrome.’’ European Journal of Pediatrics 26 (August
2004): e-pub.
ORGANIZATIONS

Huntington Disease Society of America. 140 W. 22nd St.
New York, NY 10011. (800) 345-HDSA.
National Institute of Neurological Disorders and Stroke
(NINDS). NIH Neurological Institute, P. O. Box 5801,
Bethesda, MD 20824. (800) 352-9424 or (301) 496-5751.
<http://www.ninds.nih.gov>.
National Organization for Rare Disorders (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT
06813-1968. (203) 744-0100. Fax: (203) 798-2291.
<http://www.rarediseases.org>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <http://www.fda.gov>.
OTHER

Food and Drug Administration (FDA). ‘‘Grants Awarded
by the OOPD Program.’’ <http://www.fda.gov/
orphan/grants/previous.htm>.
National Institute of Neurological Disorders and Stroke
(NINDS). ‘‘Huntington’s Disease: Hope Through
Research.’’ NIH Publication No. 98-49. Bethesda, MD:
NINDS, 2005. <http://www.ninds.nih.gov/disorders/
huntington/detail_huntington.htm>.
National Institute of Neurological Disorders and Stroke
(NINDS). ‘‘NINDS Deep Brain Stimulation for
Parkinson’s Disease Information Page.’’ Bethesda,
MD: NINDS, 2004. <http://www.ninds.nih.gov/
disorders/deep_brain_stimulation/
deep_brain_stimulation.htm>.

Laith Farid Gulli, M.D.
Rebecca J. Frey, PhD

Huntington’s chorea see Huntington’s
disease
Hurler’s syndrome see
Mucopolysaccharidoses
HUS see Hemolytic-uremic syndrome
Hyaline see Respiratory distress syndrome
Hydatid see Echinococcosis
1861

Huntington disease

KEY TERMS

Hydatidiform mole

Hydatidiform mole
Definition
A hydatidiform mole is a relatively rare condition in which tissue around a fertilized egg that
normally would have developed into the placenta
instead develops as an abnormal cluster of cells.
(This is also called a molar pregnancy.) This grapelike mass forms inside of the uterus after fertilization
instead of a normal embryo. A hydatidiform mole
triggers a positive pregnancy test and in some cases
can become cancerous.

Description
A hydatidiform mole (‘‘hydatid’’ means ‘‘drop
of water’’ and ‘‘mole’’ means ‘‘spot’’) occurs in about
1 out of every 1,500 (1/1,500) pregnancies in the United
States. In some parts of Asia, however, the incidence
may be as high as 1 in 200 (1/200). Molar pregnancies
are most likely to occur in younger and older women
(especially over age 45) than in those between ages
20–40. About 1–2% of the time a woman who has
had a molar pregnancy will have a second one.
A molar pregnancy occurs when cells of the chorionic villi (tiny projections that attach the placenta to
the lining of the uterus) don’t develop correctly.
Instead, they turn into watery clusters that can’t support a growing baby. A partial molar pregnancy
includes an abnormal embryo (a fertilized egg that
has begun to grow) that does not survive. In a compete
molar pregnancy there is a small cluster of clear
blisters or pouches that don’t contain an embryo.
If not removed, about 15% of moles can become
cancerous. They burrow into the wall of the uterus
and cause serious bleeding. Another 5% will develop
into fast-growing cancers called choriocarcinomas.
Some of these tumors spread very quickly outside
the uterus in other parts of the body. Fortunately,
cancer developing from these moles is rare and
highly curable.

Causes and symptoms
The cause of hydatidiform mole is unclear; some
experts believe it is caused by problems with the chromosomes (the structures inside cells that contain
genetic information) in either the egg or sperm, or
both. It may be associated with poor nutrition, or a
problem with the ovaries or the uterus. A mole sometimes can develop from placental tissue that is left
behind in the uterus after a miscarriage or childbirth.
1862

Women with a hydatidiform mole will have a
positive pregnancy test and often believe they have a
normal pregnancy for the first three or four months.
However, in these cases the uterus will grow abnormally fast. By the end of the third month, if not earlier,
the woman will experience vaginal bleeding ranging
from scant spotting to excessive bleeding. She may
have hyperthyroidism (overproduction of thyroid
hormones causing symptoms such as weight loss,
increased appetite, and intolerance to heat).
Sometimes, the grapelike cluster of cells itself will be
shed with the blood during this time. Other symptoms
may include severe nausea and vomiting and high
blood pressure. As the pregnancy progresses, the
fetus will not move and there will be no fetal heartbeat.

Diagnosis
The physician may not suspect a molar pregnancy
until after the third month or later, when the absence
of a fetal heartbeat together with bleeding and severe
nausea and vomiting indicates something is amiss.
First, the physician will examine the woman’s
abdomen, feeling for any strange lumps or abnormalities in the uterus. A tubal pregnancy, which can be life
threatening if not treated, will be ruled out. Then the
physician will check the levels of human chorionic
gonadotropin (hCG), a hormone that is normally produced by a placenta or a mole. Abnormally high levels
of hCG together with the symptoms of vaginal bleeding, lack of fetal heartbeat, and an unusually large
uterus all indicate a molar pregnancy. An ultrasound
of the uterus to make sure there is no living fetus will
confirm the diagnosis.

Treatment
It is extremely important to make sure that all of
the mole is removed from the uterus, since it is possible
that the tissue is potentially cancerous. Often, the
tissue is naturally expelled by the fourth month of
pregnancy. In some instances, the physician will give
the woman a drug called oxytocin to trigger the release
of the mole that is not spontaneously aborted.
If this does not happen, however, a vacuum
aspiration can be performed to remove the mole. In
a procedure similar to a dilatation and curettage
(D & C), a woman is given an anesthetic (to deaden
feeling during the procedure), her cervix (the structure
at the bottom of the uterus) is dilated and the contents
of the uterus is gently suctioned out. After the mole
has been mostly removed, gentle scraping of the uterus
lining is usually performed.
GALE ENCYCLOPEDIA OF MEDICINE

Dilatation and curettage (D & C)—Dilating the
cervix and scraping the lining of the uterus with
an instrument called a curette.
Placenta—The circular, flat organ that connects the
fetus via the umbilical cord to the uterus for oxygen,
food, and elimination of wastes.

If the woman is older and does not want any
more children, the uterus can be surgically removed
(hysterectomy) instead of a vacuum aspiration because
of the higher risk of cancerous moles in this age group.
Because of the cancer risk, the physician will continue to monitor the patient for at least two months
after the end of a molar pregnancy. Since invasive
disease is usually signaled by high levels of hCG that
don’t go down after the pregnancy has ended, the
woman’s hCG levels will be checked every two
weeks. If the levels don’t return to normal by that
time, the mole may have become cancerous.
If the hCG level is normal, the woman’s hCG will
be tested each month for six months, and then every
two months for a year.
If the mole has become cancerous, treatment
includes removal of the cancerous issue and chemotherapy. If the cancer has spread to other parts of
the body, radiation will be added. Specific treatment
depends on how advanced the cancer is.
Women should make sure not to become pregnant
within a year after hCG levels have returned to normal. If a woman were to become pregnant sooner than
that, it would be difficult to tell whether the resulting
high levels of hCG were caused by the pregnancy or a
cancer from the mole.

Prognosis
A woman with a molar pregnancy often goes
through the same emotions and sense of loss as does
a woman who has a miscarriage. Most of the time, she
truly believed she was pregnant and now has suffered a
loss of the baby she thought she was carrying. In
addition, there is the added worry that the tissue left
behind could become cancerous.
In the unlikely case that the mole is cancerous the
cure rate is almost 100%. As long as the uterus was not
removed, it would still be possible to have a child at a
later time.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Carlson, Karen J., Stephanie A. Eisenstat, and Terra
Ziporyn. The Harvard Guide to Women’s Health.
Cambridge, MA: Harvard University Press, 1996.

Carol A. Turkington

Hydrocelectomy
Definition
Hydrocelectomy is a surgical procedure to remove
a hydrocele. A hydrocele is collected fluid in the membrane surrounding the testes.

Purpose
Hydrocelectomy is performed to relieve the pain
or reoccurrence of a hydrocele. Normally, hydroceles
are not very painful. They tend to be a soft swelling
in the membrane surrounding the testes. As the hydrocele grows, the scrotum gets larger. Hydroceles do
not damage the testes. The main symptom is scrotal
swelling. There are two types of hydroceles depending
on how they form. One type is seen in children,
generally shortly after birth. It is caused by a failure
of the processus vaginalis to close. Usually, surgery
isn’t used to treat hydrocele until after two years of
age because the processus vaginalis frequently closes
by itself if given extra time. In adults, hydroceles
develop slowly. Most hydroceles develop because
of blocked lymphatic flow. Hydroceles also develop
after infection, injury, or local cancer tumors.
Generally, hydroceles are treated by aspiration of
the collected fluid. To do this, a needle is inserted
into the scrotum and directed toward the hydrocele.
Once there, as much fluid as possible is removed.
Hydroceles can reoccur. Rarely, hydroceles grow
larger and cause pain. Surgery is used to remove
large or painful hydroceles. It is also the recommended procedure to remove hydroceles that reoccur after aspiration. Hydroceles are distinguished
from other testicular problems by transillumination
and scrotal ultrasound examinations.

Precautions
No special precautions are required for hydrocelectomy. It is typically performed on an outpatient
basis.
1863

Hydrocelectomy

Resources

KEY TERMS

Hydrocephalus

KEY TERMS
Aspiration—The process of removing fluids or
gases from the body by suction.
Hernia—The protrusion of an organ or tissue
through a wall that normally contains it.
Hydrocele—An accumulation of fluid in the membrane surrounding the testes (tunica vaginalis testis).

activities may be delayed for up to six weeks. The
hydrocele does not grow back.

Abnormal results
Swelling that lasts for several months is sometimes
a complication of hydrocelectomy. Infection can also
occur.
Resources
BOOKS

Description
Aspiration of the fluid in a hydrocele is usually
successful. However, aspiration may be only a temporary solution because of the potential that the
hydrocele will reoccur. Generally, surgical repair of a
hydrocele will eliminate the hydrocele. The extent
of the surgery depends on whether other factors are
present. If the hydrocele is uncomplicated, an incision
is made in the scrotum. The hydrocele is cut out,
removing the tissues involved in the hydrocele. If
there are complications present, such as a hernia, an
incision is made in the inguinal (groin) area. This
approach allows repair of hernias and other complicating factors at the same time. Patients are placed
under general anesthesia for these operations.

Preparation
A physician or nurse will explain the procedure
and, in some cases, the need for a temporary drain to
be inserted. The drain lessens the chance of infection
and prevents fluid build-up.

Way, Lawrence W., editor. Current Surgical Diagnosis and
Treatment. 10th ed. Stamford: Appleton & Lange, 1994.

Hydrocephalus
Definition
Hydrocephalus is an abnormal expansion of cavities (ventricles) within the brain that is caused by the
accumulation of cerebrospinal fluid. Hydrocephalus
comes from two Greek words: hydros means water and
cephalus means head.
There are two main varieties of hydrocephalus:
congenital and acquired. An obstruction of the cerebral aqueduct (aqueductal stenosis) is the most frequent cause of congenital hydrocephalus. Acquired
hydrocephalus may result from spina bifida, intraventricular hemorrhage, meningitis, head trauma, tumors,
and cysts.

Aftercare
Following surgery, the patient usually only needs
a follow-up examination several weeks after the surgery to examine the incision and to check for signs of
infection.

Risks
There is a slight risk of infection and internal
hemorrhage as well as a chance of excessive bleeding
from the surgical incision.

Normal results
There may be swelling of the scrotum for up to a
month. The patient is able to resume most activities
within 7–10 days, although heavy lifting and sexual
1864

Description
Hydrocephalus is the result of an imbalance
between the formation and drainage of cerebrospinal
fluid (CSF). Approximately 500 milliliters (about a
pint) of CSF is formed within the brain each day, by
epidermal cells in structures collectively called the
choroid plexus. These cells line chambers called ventricles that are located within the brain. There are four
ventricles in a human brain. Once formed, CSF
usually circulates among all the ventricles before it is
absorbed and returned to the circulatory system. The
normal adult volume of circulating CSF is 150 ml. The
CSF turn-over rate is more than three times per day.
Because production is independent of absorption,
reduced absorption causes CSF to accumulate within
the ventricles.
GALE ENCYCLOPEDIA OF MEDICINE

Both of these types lead to an elevation of the CSF
pressure within the brain. This increased pressure
pushes aside the soft tissues of the brain. This squeezes
and distorts them. This process also results in damage
to these tissues. In infants whose skull bones have not
yet fused, the intracranial pressure is partly relieved
by expansion of the skull, so that symptoms may not
be as dramatic. Both types of elevated-pressure hydrocephalus may occur from infancy to adulthood.
A third type of hydrocephalus, called ‘‘normal
pressure hydrocephalus,’’ is marked by ventricle enlargement without an apparent increase in CSF pressure.
This type affects mainly the elderly.
Hydrocephalus has a variety of causes including:


congenital brain defects



hemorrhage, either into the ventricles or the subarachnoid space



infection of the central nervous system (syphilis,
herpes, meningitis, encephalitis, or mumps)



tumor

Hydrocephalus is believed to occur in approximately one to two of every 1,000 live births. The
incidence of adult onset hydrocephalus is not known.
There is no known way to prevent hydrocephalus.

Causes and symptoms
Hydrocephalus that is congenital (present at birth) is
thought to be caused by a complex interaction of genetic
and environmental factors. Aqueductal stenosis, an
obstruction of the cerebral aqueduct, is the most frequent
cause of congenital hydrocephalus. As of 2001, the genetic
factors are not well understood. According to the British
Association for Spina Bifida and Hydrocephalus, in very
rare circumstances, hydrocephalus is due to hereditary
factors, which might affect future generations.
Signs and symptoms of elevated-pressure hydrocephalus include:


headache



nausea and vomiting, especially in the morning

GALE ENCYCLOPEDIA OF MEDICINE



lethargy



disturbances in walking (gait)



double vision



subtle difficulties in learning and memory



delay in children achieving developmental milestones

Hydrocephalus

There are three different types of hydrocephalus.
In the most common variety, reduced absorption
occurs when one or more passages connecting the
ventricles become blocked. This prevents the movement of CSF to its drainage sites in the subarachnoid
space just inside the skull. This type of hydrocephalus
is called ‘‘noncommunicating.’’ In a second type, a
reduction in the absorption rate is caused by damage
to the absorptive tissue. This variety is called ‘‘communicating hydrocephalus.’’

Irritability is the most common sign of hydrocephalus in infants. If this is not treated, it may lead
to lethargy. Bulging of the fontanelles, or the soft spots
between the skull bones, may also be an early sign.
When hydrocephalus occurs in infants, fusion of the
skull bones is prevented. This leads to abnormal
expansion of the skull.
Symptoms of normal pressure hydrocephalus
include dementia, gait abnormalities, and incontinence
(involuntary urination or bowel movements).

Diagnosis
Imaging studies—x ray, computed tomography
scan (CT scan), ultrasound, and especially magnetic
resonance imaging (MRI)—are used to assess the presence and location of obstructions, as well as changes in
brain tissue that have occurred as a result of the
hydrocephalus. Lumbar puncture (spinal tap) may be
performed to aid in determining the cause when infection is suspected.

Treatment
The primary method of treatment for both elevated and normal pressure hydrocephalus is surgical
installation of a shunt. A shunt is a tube connecting the
ventricles of the brain to an alternative drainage site,
usually the abdominal cavity. A shunt contains a oneway valve to prevent reverse flow of fluid. In some
cases of non-communicating hydrocephalus, a direct
connection can be made between one of the ventricles
and the subarachnoid space, allowing drainage without a shunt.
Installation of a shunt requires lifelong monitoring by the recipient or family members for signs of
recurring hydrocephalus due to obstruction or failure
of the shunt. Other than monitoring, no other management activity is usually required.
Some drugs may postpone the need for surgery
by inhibiting the production of CSF. These include
acetazolamide and furosemide. Other drugs that are
used to delay surgery include glycerol, digoxin, and
isosorbide.
Some cases of elevated pressure hydrocephalus
may be avoided by preventing or treating the
1865

Hydronephrosis

ORGANIZATIONS

KEY TERMS
Cerebral ventricles—Spaces in the brain that are
located between portions of the brain and filled
with cerebrospinal fluid.
Cerebrospinal fluid—Fluid that circulates throughout the cerebral ventricles and around the spinal
cord within the spinal canal.
Choroid plexus—Specialized cells located in the
ventricles of the brain that produce cerebrospinal
fluid.
Fontanelle—One of several ‘‘soft spots’’ on the
skull where the developing bones of the skull
have yet to fuse.
Shunt—A small tube placed in a ventricle of the
brain to direct cerebrospinal fluid away from the
blockage into another part of the body.
Stenosis—The constricting or narrowing of an
opening or passageway.
Subarachnoid space—The space between two
membranes surrounding the brain, the arachnoid
and pia mater.

Association for Spina Bifida and Hydrocephalus. 42 Park
Rd., Peterborough, PE1 2UQ. UK 0173 355 5988. Fax:
017 3355 5985. postmaster@asbah.org. <http://
www.asbah.demon.co.uk>.
Hydrocephalus Foundation, Inc., (HyFI). 910 Rear
Broadway, Saugus, MA 01906. (781) 942-1161.
HyFI1@netscape.net. <http://
www.hydrocephalus.org>.
OTHER

‘‘Hydrocephalus.’’ American Association of Neurological
Surgeons/Congress of Neurological Surgeons.
<http://www.neurosurgery.org/pubpages/patres/
hydrobroch.html>.
‘‘Hydrocephalus.’’ Institute for Neurology and Neurosurgery.
Beth Israel Medical Center, New York, NY.
<http://nyneurosurgery.org/child/hydrocephalus/
hydrocephalus.htm>.
‘‘Hydrocephalus.’’ National Library of Medicine.
MEDLINEplus. <http://www.nlm.nih.gov/
medlineplus/hydrocephalus.html>.

L. Fleming Fallon, MD, PhD, DrPH

Hydrochlorothiazide see Diuretics
Hydrocodone see Analgesics, opioid
Hydrogen peroxide see Antiseptics

infectious diseases which precede them. Prenatal diagnosis of congenital brain malformation is often possible, offering the option of family planning.

Prognosis
The prognosis for elevated-pressure hydrocephalus depends on a wide variety of factors, including the
cause, age of onset, and the timing of surgery. Studies
indicate that about half of all children who receive
appropriate treatment and follow-up will develop
IQs greater than 85. Those with hydrocephalus at
birth do better than those with later onset due to
meningitis. For individuals with normal pressure
hydrocephalus, approximately half will benefit by the
installation of a shunt.
Resources
BOOKS

Toporek, Chuck, and Kellie Robinson. Hydrocephalus: A
Guide for Patients, Families & Friends. Cambridge,
Mass.: O’Reilly &Associates, 1999.
PERIODICALS

‘‘Hydrocephalus.’’ Review of Optometry 137, no. 8 (August
15, 2000): 56A.
1866

Hydronephrosis
Definition
Hydronephrosis is the swelling of the kidneys
when urine flow is obstructed in any of part of the
urinary tract. Swelling of the ureter, which always
accompanies hydronephrosis, is called hydroureter.
Hydronephrosis implies that a ureter and the renal
pelvis (the connection of the ureter to the kidney) are
overfilled with urine.

Description
The kidneys filter urine out of the blood as a waste
product. It collects in the renal pelvis and flows down
the ureters into the bladder. The ureters are not simple
tubes, but muscular passages that actively propel urine
into the bladder. At their lower end is a valve (the
ureterovesical junction) that prevents urine from flowing backward into the ureter. The bladder stores urine.
The prostate gland surrounds the bladder outlet in
males. Urine then flows through the urethra and out
of the body as a waste product.
GALE ENCYCLOPEDIA OF MEDICINE

Obstructed flow anywhere along the drainage
route can cause swelling of the upper urinary tract,
but if the obstruction is below the bladder, the ureterovesical valve will protect the upper tract to a certain
extent. Even then, with no place to go, the urine will
back up all the way to its source. Eventually, the back
pressure causes kidney function to deteriorate.
Obstruction need not be complete for problems to
arise. Intermittent or partial obstruction is far more
common than complete blockage, allowing time for
the parts to enlarge gradually. Furthermore, if a ureterovesical valve is absent or incompetent, the pressure
generated by bladder emptying will force urine backward into the ureter and kidney, causing dilation even
without mechanical obstruction.

Causes and symptoms
Causes are numerous. Various congenital deformities of the ureter may sooner or later produce back
pressure. Kidney stones are a common cause. They
form in the renal pelvis and become lodged in the
kidney, usually at the ureterovesical junction. In older
men, the continued growth of the prostate gland leads
commonly to restricted urine flow out of the bladder.
Prostate cancer, and cancer anywhere else along the
urine pathways, can obstruct flow. Pregnancy normally
causes ureteral obstruction from the pressure of the
enlarged uterus (womb) on the ureters.
Symptoms relate to the passage of urine.
Sometimes, urine may be difficult to pass, irregular,
or uncontrolled. Pain from distension of the structures
is present. Blood in the urine may be visible, but it is
usually microscopic.
In all cases where bodily fluids cannot flow freely,
infection is inevitable. Symptoms of urinary infection
may include:


painful, burning urine



cloudy urine



pain in the back, flank, or groin



fever, sweats, chills, and generalized discomfort

Patients often mistake a serious urinary infection
for the flu.

Diagnosis
If the bladder is significantly distended, it can be
felt through the abdomen. An analysis of the urine
GALE ENCYCLOPEDIA OF MEDICINE

may reveal blood (if there is a stone), infection, or
chemical changes suggesting kidney damage. Blood
tests may also detect a decrease in kidney function.
All urinary obstructions will undergo imaging
of some sort. Beginning with standard x rays to look
for stones, radiologists, physicians specializing in the
use of radiant energy for diagnostic purposes, will
select from a wide array of tests. Ultrasound is simple,
inexpensive, and very useful for these conditions.
Standard x rays can be enhanced with contrast agents
in several ways. If the kidneys are functioning, they will
filter an x ray dye out of the blood and concentrate it in
the urine, giving excellent pictures and also an assessment of kidney function. For better images of the lower
urinary tract, contrast agents can be instilled from
below. This is usually done with a cystoscope placed
in the bladder. Through the cystoscope, a small tube
can be threaded into the ureter through the ureterovesical valve, allowing dye to be injected all the way up to
the kidney. CT and MRI scanning provide miraculous
detail, more than is often needed for this condition.

Treatment
The obstruction must be relieved, even if it is partial
or functional, as in the case of reflux from the bladder.
If not, the kidney will ultimately be damaged, infection
will appear, or both. The task may be as simple as
placing a catheter through a restricting prostate or as
complicated as removing a cancerous bladder and
rebuilding a new one with a piece of bowel. In some
cases, a badly damaged kidney may have to be removed.

Alternative treatment
Catheters or other urinary diversions may be better for weak or ill patients who cannot tolerate more
extensive procedures. There is support using botanical
medicine that can help the patient using a catheter
avoid infections. Consultation with a trained health
care practitioner is necessary.

Prognosis
After relief of the obstruction, a kidney may react
with a brief flood of urine, but if the obstruction has
been of short duration, normal kidney function will
return. If one kidney is destroyed, the other will compensate for the lost organ.

Prevention
Kidney stones can be prevented by dietary changes
and medication. Prompt evaluation of infections and
1867

Hydronephrosis

Because the urinary tract is closed save for the one
opening at the bottom, urine cannot escape. Instead,
the parts distend. Rupture is rare unless there is violent
trauma like an automobile accident.

Hydrotherapy

KEY TERMS

V I N Z E N Z P R I E S S N I T Z (1799–1851)

Catheter—A tube placed into the body that allows
fluids to pass through it.
Contrast agent—Substances that cast shadows on x
rays or other imaging methods.

Hydrotherapy inventor Vinzenz Priessnitz was the
son of a Silesian farmer from a remote Austrian territory in
the Jeseniky Mountains. From the age of 12, Priessnitz
dutifully provided for his blind father, his elderly mother,
and his sister. His formal education was sporadic at best.
However, Priessnitz possessed a level head and a high
degree of intelligence along with a keen and active mind.
As he matured he became extremely aware of his surroundings in nature.

CT and MRI—Two high technology methods of
creating images of internal organs. Computerized
axial tomography (CT or CAT) uses x rays, while
magnetic resonance imaging (MRI) uses magnet
fields and radio-frequency signals. Both construct
images using a computer.
Cystoscope—A pencil-thin instrument that allows
viewing and operating inside the urinary system.
Renal pelvis—The middle section of the kidney
where urine first collects after filtration from the
blood.

urinary complaints will usually detect problems early
enough to prevent long-term complications.
Resources
ORGANIZATIONS

American Association of Kidney Patients. 100 S. Ashley Dr.,
#280, Tampa, FL 33602. (800) 749-2257. <http://
www.aakp.org>.
American Kidney Foundation. 6110 Executive Boulevard,
#1010, Rockville, MD 20852. (800) 638-8299.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.

J. Ricker Polsdorfer, MD

Hydrotherapy
Definition
Hydrotherapy, or water therapy, is the use of
water (hot, cold, steam, or ice) to relieve discomfort
and promote physical well-being.

Purpose
Hydrotherapy can soothe sore or inflamed muscles and joints, rehabilitate injured limbs, lower fevers,
soothe headaches, promote relaxation, treat burns and
frostbite, ease labor pains, and clear up skin problems.
The temperature of water used affects the therapeutic
1868

At age 16, Priessnitz fell from a horse and was seriously hoofed by the animal. He received the morbid
prognosis that he might be crippled at best, or might die
at worst. He set to treating his own chest wound with cold
packs, in emulation of a doe that he had once observed
bathing a wound in a cool mountain stream. The hydrotherapy regimen proved highly effective and drew considerable attention to his small hometown of Gräfenberg.
In 1822 he rebuilt the family home, renovating its
wooden frame into a solid brick spa structure. The spa,
known as the castle, housed as many as 1,500 guests
each year by 1939. Among the guests were medical
professionals who were intent upon exposing the therapy
as a sham.
Detractors notwithstanding, word of the simple and
effective treatment spread to Vienna, where Priessnitz
traveled on occasion to provide counsel at the emperor’s
court. Priessnitz, for his remarkable discovery, received
the Austrian Gold Civil Merit Medal First Class, the
highest civilian honor of the Austrian government.
Priessnitz died on November 28, 1851. He was
survived by a wife, Zofie Priessnitz, and a young son,
Vinzenz Pavel. Joseph Schindler took over the operation
of the spa at Gräfenberg following the death of its
founder.

properties of the treatment. Hot water is chosen for its
relaxing properties. It is also thought to stimulate the
immune system. Tepid water can also be used for
stress reduction, and may be particularly relaxing in
hot weather. Cold water is selected to reduce inflammation. Alternating hot and cold water can stimulate
the circulatory system and improve the immune
system. Adding herbs and essential oils to water can
enhance its therapeutic value. Steam is frequently used
as a carrier for essential oils that are inhaled to treat
respiratory problems.
Since the late 1990s, hydrotherapy has been used
in critical care units to treat a variety of serious conditions, including such disorders of the nervous system
as Guillain-Barré syndrome.
GALE ENCYCLOPEDIA OF MEDICINE



Showers. Showers are often prescribed to stimulate
the circulation. Water jets from a shower head are
also used to massage sore muscles. In addition, showering hydrotherapy has been shown to be preferable
to immersion hydrotherapy for treating burn
patients.



Moist compresses. Cold, moist compresses can
reduce swelling and inflammation of an injury.
They can also be used to cool a fever and treat a
headache. Hot or warm compresses are useful for
soothing muscle aches and treating abscesses.



Steam treatments and saunas. Steam rooms and saunas are recommended to open the skin pores and
cleanse the body of toxins. Steam inhalation is prescribed to treat respiratory infections. Adding botanicals to the steam bath can increase its therapeutic
value.



Internal hydrotherapy. Colonic irrigation is an enema
that is designed to cleanse the entire bowel.
Proponents of the therapy say it can cure a number
of digestive problems. Douching, another form of
internal hydrotherapy, directs a stream of water
into the vagina for cleansing purposes. The water
may or may not contain medications or other substances. Douches can be self-administered with kits
available at most drug stores.

Origins
The therapeutic use of water has a long history.
Ruins of an ancient bath were unearthed in Pakistan
and date as far back as 4500 B.C. Bathhouses were an
essential part of ancient Roman culture. The use of
steam, baths, and aromatic massage to promote well
being is documented since the first century. Roman
physicians Galen and Celsus wrote of treating patients
with warm and cold baths in order to prevent disease.
By the seventeenth and eighteenth centuries, bathhouses were extremely popular with the public
throughout Europe. Public bathhouses made their
first American appearance in the mid 1700s.
In the early nineteenth century, Sebastien Kneipp,
a Bavarian priest and proponent of water healing,
began treating his parishioners with cold water applications after he himself was cured of tuberculosis
through the same methods. Kneipp wrote extensively
on the subject, and opened a series of hydrotherapy
clinics known as the Kneipp clinics, which are still in
operation today. Around the same time in Austria,
Vincenz Priessnitz was treating patients with baths,
packs, and showers of cold spring water. Priessnitz
also opened a spa that treated over 1,500 patients in
its first year of operation, and became a model for
physicians and other specialists to learn the techniques
of hydrotherapy.
Water can be used therapeutically in a number of
ways. Common forms of hydrotherapy include:

Preparations
Because of the expense of the equipment and the
expertise required to administer effective treatment,
hydrotherapy with pools, whirlpools, Hubbard
tanks, and saunas is best taken in a professional
healthcare facility, and/or under the supervision of a
healthcare professional. However, baths, steam inhalation treatments, and compresses can be easily administered at home.



Whirlpools, jacuzzis, and hot tubs. These soaking
tubs use jet streams to massage the body. They are
frequently used by physical therapists to help injured
patients regain muscle strength and to soothe joint
and muscle pain. Some midwives and obstetricians
also approve of the use of hot tubs to soothe the pain
of labor.



Pools and Hubbard tanks. Physical therapists and
rehabilitation specialists may prescribe underwater
pool exercises as a low-impact method of rebuilding
muscle strength in injured patients. The buoyancy
experienced during pool immersion also helps ease
pain in conditions such as arthritis.

Warm to hot bath water should be used for relaxation purposes, and a tepid bath is recommended for
reducing fevers. Herbs can greatly enhance the therapeutic value of the bath for a variety of illnesses and
minor discomforts.

Baths. Tepid baths are prescribed to reduce a fever.
Baths are also one of the oldest forms of relaxation
therapy. Aromatherapists often recommend adding
essential oils of lavender (Lavandula angustifolia) to a
warm to hot bath to promote relaxation and stress
reduction. Adding Epsom salts (magnesium sulfate)
or Dead Sea salts to a bath can also promote relaxation and soothe rheumatism and arthritis.

Herbs for the bath can be added to the bath in two
ways—as essential oils or whole herbs and flowers.
Whole herbs and flowers can be placed in a muslin or
cheesecloth bag that is tied at the top to make an
herbal bath bag. The herbal bath bag is then soaked
in the warm tub, and can remain there throughout the
bath. When using essential oils, add five to 10 drops of
oil to a full tub. Oils can be combined to enhance their



GALE ENCYCLOPEDIA OF MEDICINE

Bath preparations

1869

Hydrotherapy

Description

Hydrotherapy

therapeutic value. Marjoram (Origanum marjorana) is
good for relieving sore muscles; juniper (Juniperus
communis) is recommended as a detoxifying agent for
the treatment of arthritis; lavender, ylang ylang
(Conanga odorata), and chamomile (Chamaemelum
nobilis) are recommended for stress relief; cypress
(Cupressus sempervirens), yarrow (Achillea millefolium), geranium (Pelargonium graveolens), clary sage
(Savlia sclaria), and myrtle (Myrtus communis) can
promote healing of hemorrhoids; and spike lavender
and juniper (Juniperus communis) are recommended
for rheumatism.
To prepare salts for the bath, add one or two
handfuls of epsom salts or Dead Sea salts to boiling
water until they are dissolved, and then add them to
the tub.
A sitz bath, or hip bath, can also be taken at home
to treat hemorrhoids and promote healing of an episiotomy. There is special apparatus available for taking a seated sitz bath, but it can also be taken in a
regular tub partially filled with warm water.
Steam inhalation
Steam inhalation treatments can be easily administered with a bowl of steaming water and a large
towel. For colds and other conditions with nasal
congestion, aromatherapists recommend adding five
drops of an essential oil that has decongestant properties, such as peppermint (Mentha piperita) and
eucalyptus blue gum (Eucalyptus globulus). Oils that
act as expectorants, such as myrtle (Myrtus communis)
or rosemary (Rosmarinus officinalis), can also be used.
After the oil is added, the individual should lean over
the bowl of water and place the towel over head to
trap the steam. After approximately three minutes of
inhaling the steam, with eyes closed, the towel can be
removed.
Other herbs and essential oils that can be beneficial in steam inhalation include:


tea tree oil (Melaleuca alternaifolia) for bronchitis
and sinus infections



sandalwood (Santalum album), virginian cedarwood
(Juniperus virginiana), and frankincense (Boswellia
carteri) for sore throat



lavender (Lavandula angustifolia)
(Thymus vulgaris) for cough

and

thyme

Compresses
A cold compress is prepared by soaking a cloth or
cotton pad in cold water and then applying it to the
area of injury or distress. When the cloth reaches room
1870

This patient is treating his injured left leg with a whirlpool
bath. (Custom Medical Stock Photo. Reproduced by permission.)

temperature, it should be resoaked and reapplied.
Applying gentle pressure to the compress with the
hand may be useful. Cold compresses are generally
used to reduce swelling, minimize bruising, and to
treat headaches and sprains.
Warm or hot compresses are used to treat
abscesses and muscle aches. A warm compress is prepared in the same manner as a cold compress, except
steaming water is used to wet the cloth instead of cold
water. Warm compresses should be refreshed and
reapplied after they cool to room temperature.
Essential oils may be added to moist compresses
to increase the therapeutic value of the treatment.
Peppermint, a cooling oil, is especially effective when
added to cold compresses. To add oils to compresses,
place five drops of the oil into the bowl of water the
compress is to be soaked in. Never apply essential oils
directly to a cloth, as they may irritate the skin in
undiluted form.
GALE ENCYCLOPEDIA OF MEDICINE

Individuals with paralysis, frostbite, or other
conditions that impair the nerve endings and cause
reduced sensation should only take hydrotherapy
treatments under the guidance of a trained hydrotherapist, physical therapist, or other appropriate healthcare
professional. Because these individuals cannot accurately sense temperature changes in the water, they
run the risk of being seriously burned without proper
supervision. Diabetics and people with hypertension
should also consult their healthcare professional
before using hot tubs or other heat hydrotherapies.
Hot tubs, jacuzzis, and pools can become breeding
grounds for bacteria and other infectious organisms if
they are not cleaned regularly, maintained properly,
kept at the appropriate temperatures, and treated with
the proper chemicals. Individuals should check with
their healthcare provider to ensure that the hydrotherapy equipment they are using is sanitary. Those who
are using hot tubs and other hydrotherapy equipment
in their homes should follow the directions for use and
maintenance provided by the original equipment
manufacturer.
Certain essential oils should not be used by pregnant or nursing women or by people with specific illnesses or physical conditions. Individuals suffering
from any chronic or acute health condition should
inform their healthcare provider before starting treatment with any essential oil.
Essential oils such as cinnamon leaf, juniper,
lemon, eucalyptus blue gum, peppermint, and thyme
can be extremely irritating to the skin if applied in full
concentration. Oils used in hydrotherapy should
always be diluted in water before they are applied to
the skin. Individuals should never apply essential oils
directly to the skin unless directed to do so by a trained
healthcare professional and/or aromatherapist.
Colonic irrigation should only be performed by a
healthcare professional. Pregnant women should never
douche, as the practice can introduce bacteria into the
vagina and uterus. They should also avoid using hot
tubs without the consent of their healthcare provider.
The vagina is self-cleansing, and douches have been
known to upset the balance of vaginal pH and flora,
promoting vaginitis and other infections. Some studies
have linked excessive vaginal douching to increased
incidence of pelvic inflammatory disease (PID).

Side effects
Most forms of hydrotherapy are well tolerated.
There is a risk of allergic reaction (also known as
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Contact dermatitis—Skin irritation as a result of
contact with a foreign substance.
Episiotomy—An incision made in the perineum
during labor to assist in delivery and to avoid abnormal tearing of the perineum.
Essential oil—A volatile oil extracted from the
leaves, fruit, flowers, roots, or other components
of a plant and used in aromatherapy, perfumes,
and foods and beverages.
Hubbard tank—A large water tank or tub used for
underwater exercises.

contact dermatitis) for some patients using essential
oils and herbs in their bath water. These individuals
may want to test for allergic sensitization to herbs by
performing a skin patch test (i.e., rubbing a small
amount of diluted herb on the inside of their elbow
and observing the spot for redness and irritation).
People who experience an allergic reaction to an essential oil should discontinue its use and contact their
healthcare professional for further guidance.
The most serious possible side effect of hydrotherapy is overheating, which may occur when an
individual spends too much time in a hot tub or
jacuzzi. However, when properly supervised, this is a
minimal risk.

Research and general acceptance
Hydrotherapy treatments are used by both allopathic and complementary medicine to treat a wide
variety of discomforts and disorders. Not as well
accepted are invasive hydrotherapy techniques, such
as colonic irrigation, enemas, and douching. These
internal cleansing techniques can actually harm an
individual by upsetting the natural balance of the
digestive tract and the vagina. Most conventional
medical professionals agree that vaginal douches are
not necessary to promote hygiene in most women, and
can actually do more harm than good.
Resources
BOOKS

Chaitow, Leon. Hydrotherapy: Water Therapy for Health
and Beauty. Boston, MA: Element Books, 1999.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine,
Part I: Naturopathic Medicine. New York: Simon and
Schuster, 2002.
1871

Hydrotherapy

Precautions

Hyperaldosteronism

PERIODICALS

Baird, Carol L. ‘‘First-Line Treatment for Osteoarthritis:
Part 2: Nonpharmacologic Interventions and
Evaluation.’’ Orthopaedic Nursing 20 (NovemberDecember 2001): 13–20.
Barker, K. L., H. Dawes, P. Hansford, and D. Shamley.
‘‘Perceived and Measured Levels of Exertion of Patients
with Chronic Back Pain Exercising in a Hydrotherapy
Pool.’’ Archives of Physical Medicine and Rehabilitation
84 (September 2003): 1319–1323.
Cider, A., M. Schaufelberger, K. S. Sunnerhagen, and B.
Andersson. ‘‘Hydrotherapy—A New Approach to
Improve Function in the Older Patient with Chronic
Heart Failure.’’ European Journal of Heart Failure 5
(August 2003): 527–535.
Johnson, Kate. ‘‘Hydrotherapy Greatly Eases Delivery
Stress, Pain.’’ OB GYN News 34 (November 1999): 27.
Keegan, L. ‘‘Therapies to Reduce Stress and Anxiety.’’
Critical Care Nursing Clinics of North America 15
(September 2003): 321–327.
Mayhall, C. G. ‘‘The Epidemiology of Burn Wound
Infections: Then and Now.’’ Clinical Infectious Diseases
37 (August 15, 2003): 543–550.
Molter, N. C. ‘‘Creating a Healing Environment for Critical
Care.’’ Critical Care Nursing Clinics of North America
15 (September 2003): 295–304.
Taylor, S. ‘‘The Ventilated Patient Undergoing
Hydrotherapy: A Case Study.’’ Australian Critical Care
16 (August 2003): 111–115.

and loss of potassium, which leads to hypertension
(high blood pressure).

Description
Also known as Conn’s syndrome, primary aldosteronism, and secondary aldosteronism, this disorder
takes several forms. It often begins with a tumor that
produces aldosterone. In fact, approximately 60–70%
of the cases of primary aldosteronism result from
tumors in the adrenal gland area. Aldosterone is normally produced by the adrenal cortex, or the outer
portion of the gland that rests on top of each kidney.
Primary aldosteronism is due to adenoma, a typically
benign tumor in which the cells form to act as glands
or cause the glands on which they rest to overproduce.
It can cause a number of problems, most notably
hypertension. In secondary aldosteronism, factors
outside the adrenal gland may cause overproduction
of aldosterone, or overproduction of renin, an enzyme
stored in the kidney area that stimulates aldosterone
and raises blood pressure. Obstructive renal artery
disease may also cause hypertension from elevated
renin stimulating aldosterone. Oral contraceptives
have been known to increase the secretion of aldosterone in some patients. This disorder is more common in
women.

ORGANIZATIONS

The American Association of Naturopathic Physicians. 8201
Greensboro Drive, Suite 300, McLean, Virginia 22102.
(206) 298-0126. <http://naturopathic.org>.
Canadian Naturopathic Association/Association canadienne de naturopathie. 1255 Sheppard Avenue East at
Leslie, North York, ON M2K 1E2. (800) 551-4381 or
(416) 496-8633. <http://www.naturopathicassoc.ca>.

Paula Anne Ford-Martin
Rebecca J. Frey, PhD

Hydroxzine see Anti-itch drugs
Hyperactivity see Attention-deficit/
Hyperactivity disorder (ADHD)

Hyperaldosteronism
Definition
Hyperaldosteronism is a disorder which is defined
by the body’s overproduction of aldosterone, a hormone that controls sodium and potassium levels in the
blood. Its overproduction leads to retention of salt
1872

Causes and symptoms
Hyperaldosteronism is most often caused by the
invasion of adenoma. Other adrenal cancers and
hyperplasia, or the increase in the bulk of an organ
due to increased cell production, may also cause
hyperaldosteronism. Those diseases and factors influencing the adrenal and kidney functions may lead to
secondary aldosteronism. The primary symptom of
hyperaldosteronism is moderate hypertension, or
high blood pressure. In addition, a patient may experience orthostatic hypotension, or reduced blood
pressure when a person stands after lying down.
Constipation, muscle weakness (sometimes to the
point of periodic paralysis), excessive urination, excessive thirst, headache, and personality changes are also
possible symptoms. Some patients will show no
obvious symptoms.

Diagnosis
Screening tests can be conducted to pinpoint a
diagnosis of hyperaldosteronism. If a patient is taking
drugs to reduce high blood pressure, the physician
may order these drugs stopped for a time period before
conducting tests, since these drugs will affect results.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Once the physician has made a diagnosis of
hyperaldosteronism, the adrenal glands should be
checked for possible adenomas. This can be done
through imaging or with a surgical dissection of the
gland. Surgical or ablative treatment will vary
depending on the number of tumors found. Since
more than 60% of hyperaldosteronism cases are
caused by these tumors, treatment of the tumors
will help eliminate the resulting high blood pressure
in many patients. Some patients will receive antihypertensive drugs, like calcium channel blockers, to
control high blood pressure. The use of diuretics can
help control hypertension by reducing volume.
Potassium levels should be considered in the type of
diuretic ordered and the levels should be checked
throughout treatment. The most widely used drug
for treatment of hyperaldosteronism is spironolactone. This drug helps control aldosterone, but should
not be prescribed for some patients, especially those
with certain kidney diseases. Spironolactone has
several possible adverse effects, depending on the
dosage. In all cases of hyperaldosteronism, the treatment should be carefully based on the specific type or
underlying cause of the disorder.

Alternative treatment
Patients may choose to work with their physician
or alternative provider to control hypertension with
diet, stress reduction (including massage, meditation,
biofeedback, and yoga), and other remedies. Blood
pressure elevation needs to be controlled and monitored by frequent blood pressure measurements.
There is no alternative treatment known for the underlying adenoma.

Prognosis
Hyperaldosteronism carries with it all the possible
complications of high blood pressure, including thickening of arterial walls and a higher risk of angina,
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Ablative—Used to describe a procedure involving
removal of a tissue or body part, or destruction of its
function.
Adenoma—A growth of cells, usually a benign
tumor, that forms a gland or gland-like substance.
These tumors can secrete hormones or cause
changes in hormone production in nearby glands.
Adrenal—Refers to the glands which sit on top of
each kidney and that secrete various hormones.
Antihypertensive—Used to describe drugs or treatments designed to control hypertension, or high
blood pressure.
Diuretic—A substance or drug that is taken to promote the formation and release of urine. In the
treatment of high blood pressure, diuretics can
help reduce the overall fluid volume in the body.
Renal—Relating to the kidney. The renal artery is
one of two branches of the large blood vessel in the
stomach area that serves the kidneys, ureters (tubes
that carry urine from the kidney to the bladder) and
adrenal glands.

kidney failure, stroke, or heart attack. Another possible, and less reversible complication than hypertension, is kidney damage. When primary aldosteronism
is caused by a solitary adenoma, the prognosis is good.
Once this tumor is removed, blood pressure will drop,
and 70% of these patients have full remission. Patients
whose hyperaldosteronism results from adrenal
hyperplasia will remain hypertensive. However, in up
to 70% of patients, blood pressure can be reduced
somewhat with drug therapy. Many patients will be
faced with the prospect of controlling their hypertension for the remainder of their lives.

Prevention
There is no known prevention for most causes of
hyperaldosteronism.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
American Society of Hypertension. 515 Madison Ave., Suite
1212, New York, NY 10022. (212) 644-0650. <http://
www.ash-us.org>.
1873

Hyperaldosteronism

Blood and urine tests may be conducted to check
for levels of aldosterone, potassium levels, or renin
activity. A computed tomography scan (CT scan)
may be ordered to detect tumors as small as five
to seven mm. These combined tests approach 95%
accuracy for detecting aldosterone-producing adenoma. Laboratory findings recording blood pressure,
edema, and aldosterone and plasma renin activity can
help the physician differentiate between primary
aldosteronism and secondary aldosteronism.

Hyperbaric Chamber

National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222.
<http://www.nhlbi.nih.gov>.
OTHER

Hypertension Network. <http://www.bloodpressure.com>.

Teresa Odle

Hyperbaric Chamber
Definition
A hyperbaric chamber is a room that allows an
individual to breathe 100% pure oxygen at greater
than 1 standard atmosphere of pressure.

Purpose
Hyperbaric chambers are used to deliver hyperbaric oxygen therapy (HBOT). HBOT was developed
to treat underwater divers suffering from decompression
sickness (the bends). It has since been approved by the
Undersea and Hyperbaric Medical Society for 13
conditions including:


air or gas embolism



carbon monoxide (CO) poisoning



smoke inhalation



gas gangrene caused by certain bacteria



decompression sickness



radiation tissue damage



thermal burns



non-healing skin grafts



crush injuries



wounds that fail to heal through conventional
treatment



serious blood loss



intracranial abscess.

Although hyperbaric therapy has become increasingly popular for other uses, especially in sports
medicine, its use is controversial. Terrell Owens of
the Philadelphia Eagles used HBOT for an ankle
injury prior to playing in the Super Bowl in 2005, but
medical professionals questioned the appropriateness
of this treatment.
1874

Precautions
Individuals who have lung disease including
asthma, emphysema, obstructive lung disease, or any
condition in which air is trapped in the lungs, are poor
candidates for this therapy and should discuss the
relative benefits and drawbacks of HBOT with their
doctor. Individuals who have had chest surgery or
who have had a central venous catheter implanted
are also at higher risk for complications. People with
seizure disorders should be carefully monitored, as
this treatment may increase the risk and severity of
seizures. People with colds or clogged ears may want
to wait to undergo HBOT, as they may experience
difficulties with pressure equalization that can
cause damage to the middle or inner ear. HBOT in
pregnancy is controversial. Individuals with diabetes
may need to adjust their glucose and insulin balance,
since HBOT slows the absorption of insulin.

Description
At normal atmospheric pressure, oxygen binds
with a molecule in red blood cells called hemoglobin.
The oxygen is carried through the body to tissues
where it is needed as the blood circulates. Under
normal conditions, almost all (about 97%) of the
available hemoglobin carries oxygen. Increasing the
atmospheric pressure does little to increase the oxygen-carrying capacity of the blood. However, under
normal conditions, only a small amount of oxygen is
dissolved in the fluid that carries the red blood cells
(blood plasma). Increasing the atmospheric pressure
to two to three times normal and breathing 100%
oxygen forces more oxygen to dissolve into the blood
plasma. In this way, hyperbaric chambers increase the
amount of oxygen circulating in the body. This can
promote healing in areas that are not receiving
adequate oxygen. The extra oxygen can also help to
cure certain infections caused by anerobic bacteria
that can live only in the absence of oxygen.
There are two types of hyperbaric chambers—
monoplace and multiplace. Monoplace chambers
accommodate a single person. The patient enters the
chamber, then it is closed and the pressure is increased.
The advantages of a monoplace chamber are that the
patient does not have to wear a mask or a hood to
receive the oxygen and the treatment regimen is
designed specifically for each individual. The major
disadvantages are that the patient is inaccessible to the
staff during treatment should an emergency arise, and
the pure oxygen atmosphere creates an increased fire
hazard. In multiplace chambers, several patients use
the same chamber simultaneously. Each person is
GALE ENCYCLOPEDIA OF MEDICINE

Hyperbaric chambers can be associated with
hospitals, but are increasingly part of free-standing
clinics. Insurance may cover the cost of treatment for
approved indications such as carbon monoxide poisoning, but may reject payment for uses that are considered
experimental or controversial. The American Board of
Medical Specialists certifies physician competency in the
undersea medicine, including the use of hyperbaric
chambers. The Baromedical Nurses Association offers
three levels of certification for hyperbaric nurses, and the
National Board of Hyperbaric Medicine Technology
certifies hyperbaric technicians. Individuals considering
hyperbaric therapy should seek facilities run by health
care providers credentialed by these organizations.

Preparation
No special preparation is needed to use a hyperbaric chamber other than educating patients about
what to expect during treatment.

Aftercare
After HBOT is complete, a period of decompression in the chamber is required until the pressure in
the chamber is equal to the pressure outside. Serious
complications can occur if decompression occurs
suddenly.

Risks
Hyperbaric chambers, because of their use of
100% oxygen, present a potential fire risk. In addition,
although hyperbaric oxygen therapy is very safe when
used correctly, complications can occur. Oxygen
poisoning, also called oxygen toxicity, can occur
when an individual is exposed to high doses of oxygen
for a prolonged period. Excess oxygen causes chemical
changes in the body that negatively affect cells and
metabolic processes. Symptoms of oxygen poisoning
include nausea, vomiting, dry cough, seizures, chest
pain, sweating, muscle twitching, ringing of the ears,
hallucinations, dizziness, shortness of breath and a
decreased level of consciousness.
Other complications can occur as the result of
increased pressure within the chamber. These include
pain and bloody discharge from congested sinuses, ear
pain, rupture of the eardrum, and bleeding from the
ear if the Eustachian tube that connects the ear to the
back of the throat is clogged and pressure on either
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Embolism—An obstruction in a blood vessel, often
caused by gas or a blood clot.
Eustachian tube—A tube of cartilage that connects
the middle ear to the back of the throat. Its purpose is
to equalize the pressure on either side of the eardrum.

side of the eardrum is not equalized. Teeth that are
infected or have been repaired may become painful or
explode if gas is trapped within them. A few individuals develop pneumothorax. This is a serious condition where air is trapped between the lungs and the
chest cavity.

Normal results
HBOT is expected to promote healing and
improve the health of individuals with conditions for
which it is approved.

Abnormal results
Under some conditions HBOT fails to cause
improvement or complications occur.
Resources
ORGANIZATION

Undersea and Hyperbaric Medicine Society. 10531
Metropolitan Avenue, Kensington, MD 20895.
310-942-7804. <www.uhns.0rg>.
OTHER

Moder, Cheryl. Hyperbaric Oxygen Therapy: Where
Medicine Meets the Deep Blue Sea, 20 February 2005
[cited 20 February 2005]. <http://www.emedicine.com/
plastic/topic526.htm>.
Neumeister, Michael. Hyperbaric Oxygen Therapy, 11
November 2004 [cited 16 February 2005]. <http://
www.emedicine.com/plastic/topic526.htm>.
Prince, Mark. Hyperbaric Oxygen, 27 October 2004 [cited 16
February 2005]. <http://www.emedicine.com/
ent/topic733.htm>.

Tish Davidson, A. M.

Hyperbaric oxygenation see Oxygen/ozone
therapy
Hyperbilirubinemia see Neonatal jaundice
1875

Hyperbaric Chamber

given oxygen through a face mask or hood, but all
patients receive the same treatment. A staff member
remains in the chamber throughout the procedure.

Hypercalcemia

of cells that produces a material substance (secretion). When the level of calcium circulating in the
blood drops, the parathyroid gland releases its
hormone. PTH then acts in three ways to restore
the normal blood calcium level. It stimulates the
absorption of more calcium in the intestine; it takes
more calcium from the bone tissue, and it causes the
kidneys to excrete more phosphate.

Hypercalcemia
Definition
Hypercalcemia is an abnormally high level of calcium in the blood, usually more than 10.5 milligrams
per deciliter of blood.

Description
Calcium plays an important role in the development and maintenance of bones in the body. It is also
needed in tooth formation and is important in other
body functions. Normally, the body maintains a
balance between the amount of calcium in food
sources and the calcium already available in the
body’s tissues. The balance can be upset if excess
amounts of calcium are eaten or if the body is unable
to process the mineral because of disease.
Calcium is one of the most important and most
abundant minerals in the human body. Dairy products
are the major source of calcium. Eggs, green leafy
vegetables, broccoli, legumes, nuts, and whole grains
provide smaller amounts. Only about 10–30% of the
calcium in food is absorbed into the body. Most
calcium is found in combination with other dietary
components and must be broken down by the digestive system before it can be used. Calcium is absorbed
into the body in the small intestine. Its absorption is
influenced by such factors as the amount of vitamin D
hormone available to aid the process and the levels
of calcium already present in the body. As much as
99% of the body’s calcium is stored in bone tissue.
A healthy person experiences a constant turnover of
calcium as bone tissue is built and reshaped. The
remaining 1% of the body’s calcium circulates in
the blood and other body fluids. Circulating calcium
plays an important role in the control of many
body functions, such as blood clotting, transmission
of nerve impulses, muscle contraction, and other
metabolic activities. In the bloodstream, calcium
maintains a constant balance with another mineral,
phosphate.
Two main control agents are vital in maintaining
calcium levels, vitamin D hormone and parathyroid
hormone. A hormone is a chemical substance that is
formed in one organ or part of the body and carried in
the blood to another organ. It can alter the function,
and sometimes the structure, of one or more organs.


Parathyroid hormone (PTH). The four parathyroid
glands are endocrine glands located next to the
thyroid gland in the neck. A gland is a cell or group

1876



Vitamin D hormone. This hormone works with parathyroid hormone to control calcium absorption and
affects the deposit of calcium and phosphate in the
bone tissue.

The kidneys also help to control calcium levels.
Healthy kidneys can increase calcium excretion almost
fivefold to maintain normal concentrations in the
body. Hypercalcemia can occur when the concentration of calcium overwhelms the ability of the kidneys
to maintain balance.

Causes and symptoms
Causes of hypercalcemia
Many different conditions can cause hypercalcemia; the most common are hyperparathyroidism and
cancer.
PRIMARY HYPERPARATHYROIDISM. Primary hyperparathyroidism is the excessive secretion of parathyroid hormone by one or more of the parathyroid
glands. It is the most common cause of hypercalcemia
in the general population. Women have this condition
more frequently than men do, and it is more common
in older people. It can appear thirty or more years after
radiation treatments to the neck. Ninety percent of the
cases of primary hyperparathyroidism are caused by a
non-malignant growth on the gland.

Hyperparathyroidism can also occur as part of a
rare hereditary disease called multiple endocrine
neoplasia. In this disease, tumors develop on the
parathyroid gland.
CANCER. People with cancer often have hypercalcemia. In fact, it is the most common life-threatening
metabolic disorder associated with cancer. Ten to
twenty percent of all persons with cancer have
hypercalcemia. Cancers of the breast, lung, head and
neck, and kidney are frequently associated with hypercalcemia. It also occurs frequently in association with
certain cancers of the blood, particularly malignant
myeloma. It is seen most often in patients with tumors
of the lung (25–35%) and breast (20–40%), according
to the National Cancer Institute. Cancer causes hypercalcemia in two ways. When a tumor grows into the
bone, it destroys bony tissue (osteolysis). When the

GALE ENCYCLOPEDIA OF MEDICINE

Because immobility causes an increase in the loss
of calcium from bone, cancer patients who are weak
and spend most of their time in bed are more prone to
hypercalcemia. Cancer patients are often dehydrated
because they take in inadequate amounts of food and
fluids and often suffer from nausea and vomiting.
Dehydration reduces the ability of the kidneys to
remove excess calcium from the body. Hormones
and diuretics that increase the amount of fluid released
by the body can also trigger hypercalcemia.
OTHER CAUSES. Other conditions can cause
hypercalcemia. Excessive intake of vitamin D
increases intestinal absorption of calcium. During
therapy for peptic ulcers, abnormally high amounts
of calcium antacids are sometimes taken. Over use of
antacids can cause milk-alkali syndrome and hypercalcemia. Diseases such as Paget’s, in which bone is
destroyed or reabsorbed, can also cause hypercalcemia. As in cancer or paralysis of the arms and legs,
any condition in which the patient is immobilized for
long periods of time can lead to hypercalcemia due to
bone loss.

Common symptoms
Many patients with mild hypercalcemia have no
symptoms and the condition is discovered during routine laboratory screening. Gastrointestinal symptoms
include loss of appetite, nausea, vomiting, constipation,
and abdominal pain. There may be a blockage in the
bowel. If the kidneys are involved, the individual will
have to urinate frequently during both the day and
night and will be very thirsty. As the calcium levels
rise, the symptoms become more serious. Stones may
form in the kidneys and waste products can build up.
Blood pressure rises. The heart rhythm may change.
Muscles become increasingly weak. The individual
may experience mood swings, confusion, psychosis,
and eventually, coma and death.

Diagnosis
High levels of calcium in the blood are a good
indication of hypercalcemia, but these levels may
fluctuate. Calcium levels are influenced by other compounds in the blood that may combine with calcium.
Higher calcium and lower phosphate levels may
suggest primary hyperparathyroidism. The blood
levels of protein (serum albumin) and parathyroid
hormone (PTH) are also measured in the diagnosis
GALE ENCYCLOPEDIA OF MEDICINE

of hypercalcemia. Too much PTH in the blood may
indicate primary hyperparathyroidism. Levels of calcium and phosphate in the urine should also be measured. The medical history and physical condition of
the individual must be taken into consideration, especially in the early stages of hypercalcemia when symptoms are mild.

Treatment
The treatment of hypercalcemia depends on how
high the calcium level is and what is causing the
elevation. Hypercalcemia can be life-threatening
and rapid reduction may be necessary. If the patient
has normal kidney function, fluids can be given by
vein (intravenously) to clear the excess calcium. The
amount of fluid taken in and eliminated must be
carefully monitored. If the patient’s kidneys are not
working well, acute hemodyalysis is probably the
safest and most effective method to reduce dangerous calcium levels. In this procedure, blood is circulated through tubes made of semi-permeable
membranes against a special solution that filters
out unwanted substances before returning the
blood to the body.
Drugs such as furosemide, called loop diuretics,
can be given after adequate fluid intake is established.
These drugs inhibit calcium reabsorption in the kidneys and promote urine production. Drugs that inhibit
bone loss, such as calcitonin, biphosphates, and plicamycin, are helpful in achieving long-term control.
Phosphate pills help lower high calcium levels caused
by a deficiency in phosphate. Anti-inflammatory
agents such as steroids are helpful with some cancers
and toxic levels of vitamin D.
Treatment of the underlying cause of the
hypercalcemia will also correct the imbalance.
Hyperparathyroidism is usually treated by surgical
removal of one or more of the parathyroid glands
and any tissue, other than the glands themselves, that
is producing excessive amounts of the hormone.
The hypercalcemia caused by cancer is difficult to
treat without controlling the cancer. Symptoms can be
alleviated with fluids and drug therapy as outlined
above.

Prognosis
Surgery to remove the parathyroid glands and any
misplaced tissue that is producing excessive amounts
of hormone succeeds in about 90% of all cases.
Outcome is also influenced by whether any damage
to the kidneys can be reversed.
1877

Hypercalcemia

bone is not involved, factors secreted by cancer cells
can increase calcium levels (humoral hypercalcemia of
malignancy). The two mechanisms may operate at the
same time.

Hypercholesterolemia

Resources

KEY TERMS
Calcium—A silvery-yellow metal that is the basic
element of lime and makes up about 3% of the
earth’s crust. It is the most abundant mineral in the
human body. Calcium and phosphorous combine
as calcium phosphate, the hard material of bones
and teeth.
Hormone—A chemical substance that is carried
through the blood to another part of the body,
stimulating it to change its function or structure.
Many hormones are produced by glands.
Metabolism—All the physical and chemical
changes that take place within an organism.
Milk-alkali syndrome—A chronic disorder of the
kidneys caused by the ingestion of large amounts
of calcium and alkali in the treatment of peptic
ulcer. The disorder is reversible in its early stages
but can progress to kidney failure.
Mineral—A substance that does not contain carbon
(inorganic) and is widely distributed in nature.
Minerals play an important role in human
metabolism.
Parathyroid hormone (PTH)—A chemical substance produced by the parathyroid glands. This
hormone is a major element in regulating calcium
in the body.
Vitamin D hormone—Vitamin D is a vitamin that
also acts as a hormone. Vitamin D hormone acts
with parathyroid hormone to regulate calcium
levels in the blood and to supply appropriate
amounts of calcium to all cells.

Mild hypercalcemia can be controlled through
good fluid intake and the use of effective drugs.
Hypercalcemia generally develops as a late complication of cancer and the expected outlook is grim
without effective anticancer therapy.

Prevention
People with cancer who are at risk of developing
hypercalcemia should be familiar with early symptoms
and know when to see a doctor. Good fluid intake (up
to four quarts of liquid a day if possible), controlling
nausea and vomiting, paying attention to fevers, and
keeping physically active as much as possible can help
prevent problems. Dietary calcium restriction is not
necessary because hypercalcemia reduces absorption
of calcium in the intestine.
1878

OTHER

‘‘Hypercalcemia.’’ National Cancer Institute Page. <http://
www.nci.nih.gov>.

Karen Ericson, RN

Hypercholesterolemia
Definition
Hypercholesterolemia refers to levels of cholesterol in the blood that are higher than normal.

Description
Cholesterol circulates in the blood stream. It is an
essential molecule for the human body. Cholesterol is
a molecule from which hormones and steroids are
made. It is also used to maintain nerve cells. Between
75 and 80% of the cholesterol that circulates in a
person’s bloodstream is made in that person’s liver.
The remainder is acquired from outside sources.
Cholesterol is found in animal sources of food. It is
not found in plants.
Normal blood cholesterol level is a number
derived by laboratory analysis. A normal or desirable
cholesterol level is defined as less than 200 mg of
cholesterol per deciliter of blood (mg/dL). Blood
cholesterol is considered to be borderline when it is
in the range of 200 to 239 mg/dL. Elevated cholesterol
level is 240 mg/dL or above. Elevated blood cholesterol is considered to be hypercholesterolemia.
Cholesterol has been divided into two major categories: low-density lipoprotein (LDL), the so-called
‘‘bad’’ cholesterol, and high-density lipoprotein
(HDL), the so-called ‘‘good’’ cholesterol. Diet, exercise, smoking, alcohol, and certain illnesses can affect
the levels of both types of cholesterol. Eating a high fat
diet will increase one’s level of LDL cholesterol.
Exercising and reducing one’s weight will both
increase HDL cholesterol and lower LDL cholesterol.
The most common cause of elevated serum cholesterol is eating foods that are rich in saturated fats or
contain high levels of cholesterol. Elevated cholesterol
also can be caused by an underlying disease that
raises blood cholesterol levels such as diabetes mellitus,
kidney disease, liver disease, or hypothyroidism. It also
can be caused by an inherited disorder in which
cholesterol is not metabolized properly by the body.
GALE ENCYCLOPEDIA OF MEDICINE

Hypercholesterolemia increases the risk of heart
disease. Elevated levels of circulating cholesterol cause
deposits to form inside blood vessels. These deposits,
called plaque, are composed of fats deposited from the
bloodstream. When the deposits become sufficiently
large, they block blood vessels and decrease the flow of
blood. These deposits result in a disease process called
atherosclerosis, which can cause blood clots to form
that will ultimately stop blood flow. If this happens in
the arteries supplying the heart, a heart attack will
occur. If it happens in the brain, the result is a stroke
where a portion of brain tissue dies. Atherosclerosis
causes more deaths from heart disease than any other
single condition. Heart disease has been the leading
cause of death in the United States for the past half
century.
There is a syndrome called familial hypercholesterolemia. Affected persons have consistently high
levels of LDL. This leads to early clogging of the
coronary arteries. In turn this leads to a heart attack.
Among affected males, a first heart attack typically
occurs in their 40s to 50s. Approximately 85% of men
with this disorder have experienced a heart attack by
the time they reach 60 years of age. The incidence of
heart attacks among women with this disorder also is
increased. However, it is delayed 10 years compared to
men. The incidence of familial hypercholesterolemia is
seven out of 1,000 people.

Causes and symptoms
Hypercholesterolemia is silent. There are no
symptoms that are obvious to the naked eye. It is
diagnosed by a blood test or after a heart attack or
stroke occurs.

Diagnosis
Hypercholesterolemia is diagnosed by using a
blood test. A blood specimen is obtained after the
patient does not eat or drink anything (except water)
for 12 hours. The fasting is done to measure the LDL
and HDL cholesterol, which can only be determined
accurately in a fasting state. Some experts agree that
an acceptable limit for LDL cholesterol as 130 mg/dL,
though the National Cholesterol Education Program
Adult Treatment Panel III recommended a goal of less
than 100mg/dL. Total cholesterol of under 200 mg/dL
is thought to be an acceptable range.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
If an individual’s cholesterol is elevated, discussions with a physician should be scheduled to determine what course of treatment may be needed. Initial
treatment for hypercholesterolemia usually requires
dietary changes to reduce the intake of total fat,
saturated fat, and cholesterol. Most health care professionals will recommend that a person’s weight and
height be proportionate. In addition to diet, guidelines
recommend exercise to help bring weight and cholesterol to acceptable levels. Further, experts counsel
persons with elevated blood cholesterol levels to
increase their intake of soluble fiber. Sources of soluble fiber include bran, foods containing whole grains
and other sources of indigestible fiber such as lignin.
Physicians also recommend that patients with high
cholesterol stop smoking as part of first-line therapy
for hypercholesterolemia.
The reason for treating elevated cholesterol is to
reduce an individual’s risk of complications. If a diet
low in cholesterol and saturated fats doesn’t significantly reduce a person’s cholesterol level, medication
may be required. For every 1 percent reduction in
cholesterol level, the risk of heart disease is reduced by
2 percent. It also is possible to partially reverse atherosclerosis that has already occurred by aggressively
lowering cholesterol levels with diet and medications.
Prescription drugs are available to help lower
cholesterol levels in the blood. These may be used as
first-line therapy in high-risk patients or after about
three months of dietary and lifestyle therapy.
Cholestyramine, cholestipol, lovastatin, simvastatin,
pravastatin, fluvaststin, rosuvastatin, and gemfibrazol
are some of the drugs approved for use in the United
States. The most often prescribed group of drugs are
the statins, which also have been shown in some
studies to reduce risk of depression and dementia.

Alternative treatment
There are advocates of treatment using vitamins,
minerals and antioxidant substances in relatively high
amounts. These amounts generally exceed those provided by the Food and Drug Administration in its
Minimum Daily Requirements (MDR). Advocates
of such therapies also emphasize increased levels of
exercise, attaining an ideal body weight and increasing
levels of fiber in one’s diet.
Some people have advocated the use of garlic, soy
and isoflavones to lower serum cholesterol levels. In
2003, enriched green tea was found to be an effective
addition to a low-fat diet for lowering LDL cholesterol in adults.
1879

Hypercholesterolemia

Obesity, which generally results from eating a diet high
in fat, also can lead to elevated cholesterol levels in the
blood. This is because obesity itself leads the body to
produce excessive amounts of cholesterol.

Hypercholesterolemia

Prognosis

KEY TERMS

The prognos is in direct proportion to serum cholesterol levels. People with hypercholesterolemia are at
high risk of dying from heart disease.

Atherosclerosis—A disease process whereby
plaques of fatty substances are deposited inside
arteries, reducing the inside diameter of the vessels
and eventually causing damage to the tissues
located beyond the site of the blockage.

Many studies have looked at the relationship
between elevated cholesterol levels, increased risk for
heart attack and death. In one investigation of
relatively young males who had no known heart disease, cholesterol levels were measured and participants
were followed for six years. During this time, all heart
attacks and deaths that occurred among participants
were recorded. As serum cholesterol levels increased,
so did the risk of experiencing a fatal heart attack. The
risk of a fatal heart attack was approximately five
times higher among persons having cholesterol
levels of 300 mg/dL or more compared to those with
cholesterol levels below 200 mg/dL.
The Framingham Heart Study is an ongoing
research effort. Cholesterol levels, smoking habits,
heart attack rates, and deaths in the population of an
entire town have been recorded for over 40 years.
After 30 years, more than 85% of persons with cholesterol levels of 180 mg/dL or less were still alive;
almost a third of those with cholesterol levels greater
than 260 mg/dL had died.

Prevention
Experts suggest the following steps to maintain
serum cholesterol within normal limits: an important
component is to maintain a normal weight for height
and to reduce one’s weight if it is inappropriate for
height. Changing dietary habits by reducing the amount
of fat and cholesterol consumed is advised. Doctors
recommend avoiding smoking by not starting or quitting
if currently a smoker. Increasing levels of fiber in the diet
by including foods such as beans, raw fruits, whole
grains and vegetables is receommended. It is important
to exercise on a regular basis. Aerobic exercise is
especially helpful in reducing serum cholesterol levels.
People from families with a strong history of early
heart attacks should be evaluated with a lipid screen.
Proper diet, exercise and the use of effective drugs can
reduce serum lipid levels.
Nutrition and cardiac experts offer the following
suggestions:


purchasing low-fat or fat-free dairy products such as
milk, cheese, sour cream, and yogurt



eating lean red meats, chicken without skin, and fish



reducing consumption of foods high in saturated fat
such as french fries

1880

Coronary artery—One of five vessels that supply
blood to the heart.
Deciliter (dL)—100 cubic centimeters (cc).
High density lipoprotein (HDL)—A fraction of total
serum lipids, the so called ‘‘good’’ cholesterol.
Low density lipoprotein (LDL)—A fraction of total
serum lipids, the so called ‘‘bad’’ cholesterol.



avoid foods that are rich sources of cholesterol such
as eggs, liver, cheese, and bacon



eating smaller servings



keeping a food journal and writing down everything
eaten each day



prepare food by microwaving, boiling, broiling, or
baking food instead of frying



trimming the fat from meat before cooking it.

Resources
BOOKS

Braunwald, Eugene, Douglas Zipes, and Perter Libby. Heart
Disease: A Textbook of Cardiovascular Medicine. 6th
ed. Philadelphia: Saunders, 2001.
Foody, J.M, and Eugene Braunwald. Preventive Cardiology:
Strategies for the Prevention and Treatment of Coronary
Artery Disease. Totowa, NJ: Humana Press, 2001.
Hiatt, William R. ‘‘Atheroclerotic peripheral arterial
disease.’’ In Cecil Textbook of Medicine, edited by Lee
Goldman and J. Claude Bennett, 21st ed. Philadelphia:
W.B. Saunders, 2000, pp. 357-362.
Hiatt, William R., Judith Regensteiner, and Alan T. Hirsch.
Peripheral Arterial Disease Handbook. Boca Raton,
FL: CRC Press, 2001.
Silver, Malcom, and Schoen Gottleib. Cardiovascular
Pathology. 3rd ed. Boston, Churchill Livingstone, 2001.
PERIODICALS

Aronow, Wilbert S. ‘‘Hypercholesterolemia: The Evidence
Supports Use of Statins.’’ Geriatrics August 2003: 18.
‘‘Cholesterol-lowering Effect of Green Tea.’’ Nutraceuticals
International September 2003.
Jackson, P.R. ‘‘Cholesterol-lowering Therapy for Smokers.’’
The Lancet 357, no. 9260 (2001): 960–961.
‘‘Link to Cholesterol Drugs Disputed.’’ Cardiovascular
Week September 29, 2003: 73.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Heart Association, National Center. 7272
Greenville Avenue, Dallas, Texas 75231. (877)
242-4277. <http://www.americanheart.org>.
American Medical Association. 515 N. State Street,
Chicago, IL 60610. (312) 464-5000. <http://
www.ama-assn.org/>.
American Society of Nuclear Cardiology. 9111 Old
Georgetown Road, Bethesda, MD 20814-1699. (301)
493-2360. Fax: (301) 493-2376, <http://
www.asnc.org>.
OTHER

American Academy of Family Practice: <http://
www.aafp.org/afp/20000201/675.html>.
American Heart Association. <http://www.americanheart.org/Scientific/pubs/hyperchol/>.
Merck Manual. <http://www.merck.com/pubs/mmanual/
section2/chapter15/15c.htm>.
National Library of Medicine: <http://www.nlm.nih.gov/
medlineplus/ency/article/000403.htm>.

L. Fleming Fallon, Jr., MD, DrPH
Teresa G. Odle

Hypercoagulation disorders
Definition
Hypercoagulation disorders (or hypercoagulable
states or disorders) have the opposite effect of the
more common coagulation disorders. In hypercoagulation, there is an increased tendency for clotting of the
blood, which may put a patient at risk for obstruction of
veins and arteries (phlebitis or pulmonary embolism).

Description
In normal hemostasis, or the stoppage of bleeding, clots form at the site of the blood vessel’s injury.
The difference between that sort of clotting and the
clotting present in hypercoagulation is that these clots
develop in circulating blood.
This disorder can cause clots throughout the
body’s blood vessels, sometimes creating a condition
known as thrombosis. Thrombosis can lead to infarction, or death of tissue, as a result of blocked blood
GALE ENCYCLOPEDIA OF MEDICINE

supply to the tissue. However, hypercoagulability
does not always lead to thrombosis. In pregnancy,
and other hypercoagulable states, the incidence of
thrombosis is higher than that of the general population, but is still under 10%. However, in association
with certain genetic disorders, hypercoagulation disorders may be more likely to lead to thrombosis.
Hypercoagulation disorders may also be known as
hyperhomocystinemia, antithrombin III deficiency,
factor V leyden, and protein C or protein S deficiency.

Causes and symptoms
Hypercoagulation disorders may be acquired or
hereditary. Some of the genetic disorders that lead
to hypercoagulation are abnormal clotting factor V,
variations in fibrinogen, and deficiencies in proteins C
and S. Other body system diseases may also lead to
these disorders, including diabetes, sickle cell anemia,
congenital heart disease, lupus, thalassemia, polycythemia rubra vera, and others. Antithrombin III
deficiency is a hereditary hypercoagulation disorder
that affects both sexes. Symptoms include obstruction
of a blood vessel by a clot (thromboembolic disease),
vein inflammation (phlebitis), and ulcers of the lower
parts of the legs. The role of proteins C and S is a
complex one. In order for coagulation to occur, platelets (small, round fragments in the blood) help contract blood vessels to lessen blood loss and also to help
plug damaged blood vessels. However, the conversion
of platelets into actual clots is a complicated web
involving proteins that are identified clotting factors.
The factors are carried in the plasma, or liquid portion
of the blood. Proteins C and S are two of the clotting
factors that are present in the plasma to help regulate
or activate parts of the clotting process. Protein C
is considered an anticoagulant. Mutation defects in
the proteins may decrease their concentrations in
the blood, and may or may not affect their resulting
anticoagulant activity. Factor V is an unstable clotting
factor also present in plasma. Abnormal factor V
resists the changes that normally occur through the
influence of protein C, which can also lead to hypercoagulability. Prothrombin, a glycoprotein that converts to thrombin in the early stage of the clotting
process, is affected by the presence of these proteins,
as well as other clotting factors.

Diagnosis
The diagnosis of hypercoagulation disorders is
completed with a combination of physical examination,
medical history, and blood tests. An accurate medical
history is important to determine possible symptoms
1881

Hypercoagulation disorders

Mechcatie, Elizabeth. ‘‘FDA Okays Rosuvastatin for
Hypercholeterolemia: Most Potent Statin to Date.’’
Internal Medicine News September 1, 2003: 30–31.
Shamir R., A. Lerner, and E. A. Fisher.
‘‘Hypercholesterolemia in Children.’’ Israel Medical
Association Journal 2, no. 10 (2000): 767–771.

Hyperemesis gravidarum

determine a person’s tendency to develop these
disorders.

KEY TERMS
Antithrombin—Any substance that counters the
effect of thrombin, an enzyme that converts fibrinogen into fibrin, leading to blood coagulation.
Congenital—Refers to a condition or disorder present at birth.
Hemostasis—The arrest of bleeding.
Heparin—An anticoagulant, or blood
‘‘dissolver.’’

clot

Polycythemia—A condition characterized by an
overabundance of red blood cells.
Thalassemia—One of a group of inherited blood
disorders characterized by a defect in the metabolism of hemoglobin, or the portion of the red blood
cells that transports oxygen throughout the blood
stream.
Thrombosis—Formation of a clot in the blood that
either blocks, or partially blocks, a blood vessel.
The thrombus may lead to infarction, or death of
tissue due to a blocked blood supply.

Resources
ORGANIZATIONS

National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222.
<http://www.nhlbi.nih.gov>.
National Hemophilia Foundation. 116 West 32nd St., 11th
Floor, New York, NY 10001. 800-424-2634.
<http://www.hemophilia.org/home.htm>.

Teresa Odle

Hyperemesis gravidarum
Definition
Hyperemesis gravidarum means excessive vomiting during pregnancy.

Description
and causes of hypercoagulation disorders. There are a
number of blood tests that can determine the presence
or absence of proteins, clotting factors, and platelet
counts in the blood. Among the tests used to detect
hypercoagulation is the Antithrombin III assay.
Protein C and Protein S concentrations can be diagnosed with immunoassay or plasma antigen level tests.

In pregnant women, nausea and vomiting (morning sickness) are common, affecting up to 80% of
pregnancies. Hyperemesis, or extreme nausea and
excessive vomiting, occur in about 1% of pregnancies.
This condition causes uncontrollable vomiting, severe
dehydration, and weight loss for the mother. However, hyperemesis gravidarum rarely causes problems
for the unborn baby.

Treatment
Coumadin and heparin anticoagulants may be
administered to reduce the clotting effects and maintain fluidity in the blood. Heparin is an anticoagulant
that prevents thrombus formation and is used primarily for liver and lung clots.

Prognosis
The prognosis for patients with hypercoagulation
disorders varies depending on the severity of the clotting and thrombosis. If undetected and untreated,
thrombosis could lead to recurrent thrombosis and
pulmonary embolism, a potentially fatal problem.

Prevention
Hereditary hypercoagulation disorders may not
be prevented. Genetic and blood testing may help
1882

Causes and symptoms
The cause of nausea and vomiting during pregnancy is unknown but may be related to the level
of certain hormones produced during pregnancy.
Hyperemesis is seen more often in first pregnancies
and multiple pregnancies (twins, triplets, etc.). The
main symptom of hyperemesis is severe vomiting,
which causes dehydration and weight loss.

Diagnosis
Although many women with morning sickness
feel like they are vomiting everything they eat, they
continue to gain weight and are not dehydrated; they
do not have hyperemesis gravidarum. Women with
this condition will start to show signs of starvation,
including weight loss. Physical examination and
laboratory tests of blood and urine samples will be
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Hospitalization is often required. Intravenous
fluids with substances that help the body conduct
nerve signals (electrolytes) may be given to correct
the dehydration and excessive acid in the blood (acidosis). Anti-nausea or sedative medications may be given
by injection to stop the vomiting. In some cases, oral
medication may be prescribed to control the nausea
and vomiting while food is reintroduced. If food
cannot be tolerated at all, intravenous nutritional supplements may be necessary. Injections of vitamin B6,
in particular, may help overcome nutritional deficiencies that often occur.

KEY TERMS
Ketonuria—The presence of large amount of
ketones in the urine. These byproducts of inadequate breakdown of nutrients indicate that the body
is in starvation.

healthy diet, getting adequate sleep, and controlling
stress may contribute to prevention or improvement
of symptoms. Several strategies may help lessen the
nausea and vomiting. Eating dry foods and limiting
fluid intake may also be helpful. Small meals should
be eaten frequently throughout the day, with a protein
snack at night. Eating soda crackers before rising from
bed in the morning may help prevent early morning
nausea. Iron supplements may cause nausea and can
be eliminated until the nausea is controlled. Sitting
upright for 45 minutes after meals may also help.
Resources
OTHER

Alternative treatment
The severe vomiting associated with hyperemesis
gravidarum requires medical attention. Milder episodes of nausea or vomiting may be reduced with
deep breathing and relaxation exercises. The use of
herbal remedies should be done with extreme caution
during pregnancy, especially in the first trimester.
Natural remedies to reduce nausea include a teaspoon
of cider vinegar in a cup of warm water, or tea made
from anise (Pinpinella anisum), fennel seed (Foeniculum
vulgare), red raspberry (Rubus idaeus), or ginger
(Zingiber officinale). Wristbands can be positioned
over acupressure points on both wrists. Aromatherapy
with lavender, rose, or chamomile can be soothing, as
can smelling ground ginger. Homeopathic remedies—
which use extremely diluted solutions as treatments—
can be safe and effective for controlling symptoms in
some women.

Prognosis
In virtually all cases, the pregnancy can continue
to the successful delivery of a healthy baby.

Prevention
Although there is no evidence that hyperemesis
gravidarum can be prevented, vomiting during pregnancy sometimes may be lessened. Maintaining a
GALE ENCYCLOPEDIA OF MEDICINE

Levy, B. T., and P. L. Brown. ‘‘Nausea and Vomiting in
Pregnancy.’’ The Virtual Hospital Page. University
of Iowa. <http://www.vh.org>.
‘‘Natural Remedies During Pregnancy: Frequently Asked
Questions.’’ Childbirth.Org. <http://www.
childbirth.org/articles/remedy.html>.

Altha Roberts Edgren

Hyperhidrosis
Definition
Hyperhidrosis is a disorder marked by excessive
sweating. It usually begins at puberty and affects the
palms, soles, and armpits.

Description
Sweating is the body’s way of cooling itself and is
a normal response to a hot environment or intense
exercise. However, excessive sweating unrelated to
these conditions can be a problem for some people.
Those with constantly moist hands may feel uncomfortable shaking hands or touching, while others with
sweaty armpits and feet may have to contend with
the unpleasant odor that results from the bacterial
1883

Hyperhidrosis

used to help diagnose the condition. One of the most
common tests used to help diagnosis and monitor
hyperemesis gravidarum is a test for ketones in the
urine. Excessive ketones in the urine (ketonuria) indicate that the body is not using carbohydrates from
food as fuel and is inadequately trying to break
down fat as fuel. Ketonuria is a sign that the body is
beginning to operate in starvation mode.

Hyperhidrosis

breakdown of sweat and cellular debris (bromhidrosis). People with hyperhidrosis often must change their
clothes at least once a day, and their shoes can be
ruined by the excess moisture. Hyperhidrosis may
also contribute to such skin diseases as athlete’s foot
(tinea pedis) and contact dermatitis.
In addition to excessive sweat production, the
texture and color of the skin itself may be affected by
hyperhidrosis. The skin may turn pink or bluish white.
Severe hyperhidrosis of the soles of the feet may produce cracks, fissures, and scaling of the skin.
Hyperhidrosis in general and axillary hyperhidrosis (excessive sweating in the armpits) in particular are
more common in the general population than was
previously thought. A group of dermatologists in
Virginia reported in 2004 that 2.8% of the United
States population, or about 7.8 million persons, have
hyperhidrosis. Of this group, slightly more than half
(4 million persons) have axillary hyperhidrosis. Onethird of the latter group, or about 1.3 million persons,
find that the condition significantly interferes with
daily activities and is barely tolerable. Only 38%,
however, had ever discussed their excessive sweating
with their doctor.

Causes and symptoms
There are three basic forms of hyperhidrosis:
emotionally induced; localized; and generalized.
Emotionally induced hyperhidrosis typically affects
the palms of the hands, soles of the feet, and the armpits.
Localized hyperhidrosis typically affects the palms,
armpits, groin, face, and the area below the breasts in
women, while generalized hyperhidrosis may affect the
entire body.
Hyperhidrosis may be either idiopathic (of
unknown cause) or secondary to fever, metabolic disorders, alcoholism, menopause, Hodgkin’s disease,
tuberculosis, various types of cancer, or the use of
certain medications. The medications most commonly
associated with hyperhidrosis are propranolol, venlafaxine, tricyclic antidepressants, pilocarpine, and
physostigmine.
Most cases of hyperhidrosis begin during childhood
or adolescence. Hyperhidrosis that begins in adult life
should prompt the doctor to look for a systemic illness,
medication side effect, or metabolic disorder.
Hyperhidrosis affects both sexes equally and may
occur in any age group. People of any race may be
affected; however, for some reason unknown as of
the early 2000s, Japanese are affected 20 times more
frequently than members of other ethnic groups.
1884

Diagnosis
Hyperhidrosis is diagnosed by patient report and
a physical examination. In many cases the physician
can directly observe the excessive sweating.
The doctor may also perform an iodine starch test,
which involves spraying the affected areas of the
patient’s body with a mixture of 500 g of water-soluble
starch and 1 g iodine crystals. Areas of the skin producing sweat will turn black.
The doctor will order other laboratory or imaging
tests if he or she suspects that the sweating is associated with another disease or disorder.

Treatment
Most over-the-counter antiperspirants are not
strong enough to effectively prevent hyperhidrosis.
To treat the disorder, doctors usually prescribe 20%
aluminum chloride hexahydrate solution (Drysol),
which the patient applies at night to the affected
areas that are then wrapped in a plastic film until
morning. Drysol works by blocking the sweat pores.
Formaldehyde- and glutaraldehyde-based solutions
can also be prescribed; however, formaldehyde may
trigger an allergic reaction and glutaraldehyde can
stain the skin (for this reason it is primarily applied
to the soles). Anticholinergic drugs may also be given.
These drugs include such medications as propantheline, oxybutynin, and benztropine.
Injections of botulinum toxin (Botox) given under
the skin work well for some patients. Botox works to
stop the excessive sweating by preventing the transmission of nerve impulses to the sweat glands. These
injections must be repeated every 4–12 months,
however.
In addition, an electrical device that emits lowvoltage current can be held against the skin to reduce
sweating. These treatments are usually conducted in
a doctor’s office on a daily basis for several weeks,
followed by weekly visits. Dermatologists also recommend that patients wear clothing made of natural or
absorbent fabrics also may help, avoid high-buttoned
collars, use talc or cornstarch, and keep underarms
shaved.
The only permanent cure for hyperhidrosis of the
palms is a surgical procedure known as a sympathectomy. To treat severe excessive sweating, a surgeon can
remove a portion of the nerve near the top of the spine
that controls palm sweat. However, not very many
neurosurgeons in the United States will perform the
procedure, because it often results in compensatory
sweating in other regions of the body. Alternatively,
GALE ENCYCLOPEDIA OF MEDICINE

Anticholinergic drugs—Drugs that block the action
of the neurotransmitter acetylcholine.
Axilla (plural, axillae)—The medical term for the
armpit.
Bromhidrosis—Bacterial breakdown of sweat and
cellular debris resulting in a foul odor.
Contact dermatitis—Skin inflammation that occurs
when the skin is exposed to a substance originating
outside of the body.
Idiopathic—Of spontaneous origin or unknown
cause. Many cases of hyperhidrosis are idiopathic.
Sympathectomy—Surgical cutting or interruption
of any of the pathways in the sympathetic nervous
system. It may be performed to control hyperhidrosis that does not respond to medications.
Sympathetic nervous system—The part of the
nervous system that originates in the lumbar and
thoracic portions of the spinal cord. It regulates
involuntary reactions to stress, including sweating
as well as heart rate, breathing rate, and digestive
secretions.
Tinea pedis—Fungal infection of the feet of the skin
characterized by dry, scaly lesions.

it is possible to surgically remove the sweat glandbearing skin of the armpits, but this is a major procedure that may require skin grafts.
More recently, liposuction under the armpits has
been successfuly used to treat hyperhydrosis in this
region of the body. The liposuction removes some
of the excess sweat glands responsible for axillary
hyperhidrosis. The procedure also has the advantage
of leaving smaller scars and being less disruptive of the
overlying skin.

Prognosis
Hyperhidrosis is not associated with increased
mortality; it primarily affects the patient’s quality of
life rather than longevity. While the condition cannot
be cured without radical surgery, it can usually be
controlled effectively.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disorders of Sweating.’’ Section 10, Chapter 124 In
GALE ENCYCLOPEDIA OF MEDICINE

The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Altman, Rachel, MD, George Kihiczak, MD, and Robert
Schwartz, MD. ‘‘Hyperhidrosis.’’ eMedicine August 18,
2004. <http://www.emedicine.com/derm/
topic893.htm>.
Licht, P. B., and H. K. Pilegaard. ‘‘Severity of
Compensatory Sweating after Thoracoscopic
Sympathectomy.’’ Annals of Thoracic Surgery 78
(August 2004): 427–431.
Strutton, D. R., J. W. Kowalski, D. A. Glaser, and P. E.
Stang. ‘‘US Prevalence of Hyperhidrosis and Impact on
Individuals with Axillary Hyperhidrosis: Results from a
National Survey.’’ Journal of the American Academy of
Dermatology 51 (August 2004): 241–248.
ORGANIZATIONS

American Academy of Dermatology (AAD). P. O. Box
4014, Schaumburg, IL 60168-4014. (847) 330-0230.
<http://www.aad.org>.

Carol A. Turkington
Rebecca J. Frey, PhD

Hyperhomocystinemia see
Hypercoagulation disorders
Hypericum perforatum see St. Johns wort

Hyperkalemia
Definition
The normal concentration of potassium in
the serum is in the range of 3.5 to 5.0 mM.
Hyperkalemia refers to serum or plasma levels of
potassium ions above 5.0 mM. The concentration of
potassium is often expressed in units of milliequivalents per liter (mEq/L), rather than in units of millimolarity (mM). Both units mean the same thing when
applied to concentrations of potassium ions.

Description
A normal adult who weighs about 70 kg contains
a total of about 3.6 moles of potassium ions in the
body. Most of this potassium (about 98%) occurs
inside various cells and organs, where its concentration is about 150 mM. This level is in contrast to the
much lower concentration found in the blood serum,
where only about 0.4% of the body’s potassium
resides. Hyperkalemia can be caused by an overall
1885

Hyperkalemia

KEY TERMS

Hyperkalemia

excess of body potassium, or by a shift from inside to
outside cells. For example, hyperkalemia can be
caused by the sudden release of potassium ions from
muscle into the surrounding fluids.
In a normal person, hyperkalemia from too much
potassium in the diet is prevented by at least three
types of regulatory processes. First, various cells and
organs act to prevent hyperkalemia by taking up
potassium from the blood. It is also prevented by the
action of the kidneys, which excrete potassium into the
urine. A third protective mechanism is vomiting.
Consumption of a large dose of potassium ions, such
as potassium chloride, induces a vomiting reflex to
expel most of the potassium before it can be absorbed.

Causes and symptoms
Hyperkalemia can occur from a variety of causes,
including the consumption of too much of a potassium
salt; the failure of the kidneys to normally excrete
potassium ions into the urine; the leakage of potassium
from cells and tissues into the bloodstream; and from
acidosis. The most common cause of hyperkalemia is
kidney (or renal) disease, which accounts for about
three quarters of all cases. Kidney function is measured
by the glomerular filtration rate, the rate at which each
kidney performs its continual processing and cleansing
of blood. The normal glomerular filtration rate is about
100 ml/min. If the kidney is damaged so that the
glomerular filtration rate is only 5 ml/min or less,
hyperkalemia may result, especially if high-potassium
foods are consumed. The elderly are at particular risk,
since many regulatory functions of the body do not
work well in this population. Elderly patients who
are being treated with certain drugs for high blood
pressure, such as spironolactone (Aldactone) and
triamterene (Dyazide), must especially be monitored
for possible hyperkalemia, as these medications
promote the retention of potassium by the kidneys.
Hyperkalemia can also be caused by a disease of
the adrenal gland called Addison’s disease. The adrenal
gland produces the hormone aldosterone that promotes the excretion of potassium into the urine by
the kidney.
Hyperkalemia can also result from injury to muscle
or other tissues. Since most of the potassium in the body
is contained in muscle, a severe trauma that crushes
muscle cells results in an immediate increase in the concentration of potassium in the blood. Hyperkalemia
may also result from severe burns or infections.
Acidic blood plasma, or acidosis, is an occasional
cause of hyperkalemia. Acidosis, which occurs in a
1886

number of diseases, is defined as an increase in the
concentration of hydrogen ions in the bloodstream. In
the body’s attempt to correct the situation, hydrogen
is taken up by muscle cells out of the blood in an
exchange mechanism involving the transfer of potassium ions into the bloodstream. This can abnormally
elevate the plasma’s concentration of potassium ions.
When acidosis is the cause of hyperkalemia, treating
the patient for acidosis has two benefits: a reversal of
both the acidosis and the hyperkalemia.
Symptoms of hyperkalemia include abnormalities
in the behavior of the heart. Heart abnormalities of
mild hyperkalemia (5.0 to 6.5 mM potassium) can be
detected by an electrocardiogram (ECG or EKG).
With severe hyperkalemia (over 8.0 mM potassium),
the heart may beat at a dangerously rapid rate (fibrillation) or stop beating entirely (cardiac arrest).
Patients with moderate or severe hyperkalemia may
also develop nervous symptoms such as tingling of the
skin, numbness of the hands or feet, weakness, or a
flaccid paralysis, which is characteristic of both hyperkalemia and hypokalemia (low plasma potassium).

Diagnosis
Hyperkalemia can be measured by acquiring a
sample of blood, preparing blood serum, and using a
potassium sensitive electrode for measuring the concentration of potassium ions. Alternatively, atomic
absorption spectroscopy can be used for measuring
potassium. Since high or low potassium levels result
in abnormalities in heart function, the electrocardiogram is usually the method of choice for the diagnosis
of both hyperkalemia and hypokalemia.

Treatment
Insulin injections are used to treat hyperkalemia
in emergency situations. Insulin is a hormone well
known for its ability to stimulate the entry of sugar
(glucose) into cells. It also provokes the uptake of
potassium ions by cells, decreasing potassium ion concentration in the blood. When insulin is used to treat
hyperkalemia, glucose is also injected. Serum potassium levels begin to decline within 30 to 60 minutes
and remain low for several hours. In non-emergency
situations, hyperkalemia can be treated with a low
potassium diet. If this does not succeed, the patient
can be given a special resin to bind potassium ions.
One such resin, sodium polystyrene sulfonate
(Kayexalate), remains in the intestines, where it
absorbs potassium and forms a complex of resin and
potassium. Eventually this complex is excreted in the
feces. A typical dose of resin is 15 grams, taken one to
GALE ENCYCLOPEDIA OF MEDICINE

Acidosis—An abnormally high acid (hydrogen ion)
concentration in blood plasma. The unit of acid
content is pH, with a lower value indicating more
acidic conditions. Blood plasma normally has a pH
of 7.35–7.45. Alkaline blood has a pH value greater
than pH 7.45. When the blood pH value is less than
7.35, the patient is in acidosis.

four times per day. The correction of hyperkalemia
with resin treatment takes at least 24 hours.

Prognosis
The prognosis for specifically correcting hyperkalemia is excellent. However, hyperkalemia is usually
caused by kidney failure, an often irreversible and
eventually fatal condition.

Prevention
Healthy people are not at risk for hyperkalemia.
Patients with renal disease and those on certain
diuretic medications must be monitored to prevent its
occurrence.
Resources
PERIODICALS

Greenberg, A. ‘‘Hyperkalemia: treatment options.’’
Seminars in Nephrology 18 (1998): 46-57.

Tom Brody, PhD

Hyperkinetic disorder see Attention-deficit/
Hyperactivity disorder (ADHD)
Hyperlipemia see Hyperlipoproteinemia
Hyperlipidemia see Hyperlipoproteinemia

Hyperlipoproteinemia
Definition
Hyperlipoproteinemia occurs when there is too
much lipid (fat) in the blood. Shorter terms that
mean the same thing are hyperlipidemia and hyperlipemia. Dyslipidemia refers to a redistribution of
cholesterol from one place to another that increases
GALE ENCYCLOPEDIA OF MEDICINE

the risk of vascular disease without increasing the total
amount of cholesterol. When more precise terms are
needed, hypercholesterolemia and hypertriglyceridemia are used.

Description
It is commonly known that oil and water do not
mix unless another substance like a detergent is added.
Yet the body needs to transport both lipids (fats) and
water-based blood within a single circulatory system.
There must be a way to mix the two, so that essential
fatty nutrients can be transported in the blood and so
that fatty waste products can be carried away from
tissues. The solution is to combine the lipids with
protein to form water-soluble packages that can be
transported in the blood.
These packages of fats are called lipoproteins.
They are a complex mixture of triglycerides, cholesterol, phospholipids and special proteins. Some of
these chemicals are fatty nutrients absorbed from the
intestines on their way to being made part of the body.
Cholesterol is a waste product on its way out of the
body through the liver, the bile, and ultimately the
bowel for excretion. The proteins and phospholipids
make the packages water-soluble.
There are five different sizes of these chemical
packages. Each package needs all four chemicals in it
to hold everything in solution. They differ in how
much of each they contain. If blood serum is spun
very rapidly in an ultracentrifuge, these five packages
will layer out according to their density. They have,
therefore, been named according to their densities—
high-density lipoproteins (HDL), low-density lipoproteins (LDL), intermediate-density lipoproteins (IDL),
very low density lipoproteins (VLDL), and chylomicrons. Only the HDLs and the LDLs will be discussed
in the rest of this article.
If there is not enough detergent in the laundry, the
oily stains will remain in the clothes. In the same way,
if the balance of chemicals in these packages is not
right, cholesterol will stay in tissues rather than being
excreted from the body. What is even worse, if the
chemical composition of these packages changes, the
cholesterol can fall out of the blood and stay where it
lands. On the other hand, a different change in the
balance can remove cholesterol from tissues where
there is too much. This appears to be exactly what is
going on in atherosclerosis. The lesions contain lots of
cholesterol.
The LDLs are overloaded with cholesterol.
A minor change in the other chemicals in this package
1887

Hyperlipoproteinemia

KEY TERMS

Hyperlipoproteinemia

will leave cholesterol behind. The HDLs have a third to
a half as much cholesterol. They seem to be able to pick
up cholesterol left behind by the LDLs. It seems that
atherosclerosis begins with tiny tears at stressed places
in the walls of the arteries. Low density lipoproteins
from the blood enter these tears, where their chemistry
changes enough to leave cholesterol behind. The cholesterol causes irritation; the body responds with
inflammation; damage and scarring follow. Eventually
the artery gets so diseased blood cannot flow through
it. Strokes and heart attacks are the result.
But if there are lots of HDLs in the blood, the
cholesterol is rapidly picked up and not allowed to
cause problems. Women before menopause have estrogen (the female hormone), which encourages the
formation of HDLs. This is the reason they have so
little vascular disease, and why they rapidly catch up
to men after menopause, when estrogen levels fall.
Replacement of estrogen after menopause has been
prescribed to for protection through the later years.
However, in 2003, the Women’s Health Initiative, a
large clinical trial involving postmenopausal women,
was halted in July 2002 because of the many detrimental effects of combined estrogen and progesterone
therapy (called hormone replacement therapy).
Among the effects was increased risk of heart disease,
sometimes within the first year of use.

kind, because everyone is at risk for it. All Type
2s have elevated cholesterol. Some have elevated
triglycerides also. The familial (genetic) versions of
Type 2 often develop xanthomas, which are yellow
fatty deposits under the skin of the knuckles, elbows,
buttocks or heels. They also may have xanthelasmas,
smaller yellow patches on the eyelids.


Type 3 appears in one in10,000 people and elevates both
triglycerides and cholesterol with consequent vascular
disease. In 2003, researchers discovered the molecular
mechanism that contributes to high triglycerides in
those with this type of hyperlipopoproteinemia.



Type 4 elevates only triglycerides and does not
increase the risk of vascular disease.



Type 5 is similar to Type 1.



Dyslipidemia refers to a normal amount of cholesterol that is mostly in LDLs, where it causes
problems.

All but Type 2 are rare and of interest primarily
because they give insight into the chemistry of blood
fats.
In addition to the above genetic causes of blood
fat disorders, a number of acquired conditions can
raise lipoprotein levels.

Cholesterol is the root of the problem, but like any
other root it cannot just be eliminated. Ninety percent
of the cholesterol in the body is created there as a waste
product of necessary processes. The solution lies in
getting it out to the body without clogging the arteries.



Diabetes mellitus, because it alters the way the body
handles its energy needs, and also affects the way it
handles fats. The result is elevated triglycerides and
reduced HDL cholesterol. This effect is amplified by
obesity.

Of course the story is much more complex. The
body has dozens of chemical processes that make up,
break down, and reconfigure all these chemicals. It is
these processes that are the targets of intervention in
the effort to cure vascular disease.



Hypothyroidism is a common cause of lipid abnormalities. The thyroid hormone affects the rate of many
chemical processes in the body, including the clearing
of fats from the blood. The consequence usually is an
elevation of cholesterol.



Kidney disease affects the blood’s proteins and consequently the composition of the fat packages. It
usually raises the LDLs.



Liver disease, depending on its stage and severity,
can raise or lower any of the blood fats.



Alcohol raises triglycerides. In moderate amounts
(if they are very moderate) it raises HDLs and can
be beneficial.



Cigarette smoking lowers HDL cholesterol, as does
malnutrition and obesity.

Diseases
Near the dawn of concern over cholesterol and
vascular disease a family of hereditary diseases was identified, all of which produced abnormal quantities of
blood fats. These diseases were called dyslipoproteinemias and came in both too many and too little varieties.
The hyperlipoproteinemias found their way into five
categories, depending on which chemical was in excess.




Type 1 has a pure elevation of triglycerides in the
chylomicron fraction. These people sometimes get
pancreatitis and abdominal pains, but they do not
seem to have an increase in vascular disease.
Type 2 appears in two distinct genetic patterns and a
third category, which is by far the most important

1888

Certain medications elevate blood fat levels.
Because some of these medications are used to treat
heart disease, it has been necessary to reevaluate their
usefulness:
GALE ENCYCLOPEDIA OF MEDICINE

Thiazides, water pills used to treat high blood
pressure, can raise both cholesterol and triglycerides.



Beta-blockers, another class of medication used to
treat high blood pressure, cortisone-like drugs, and
estrogen can raise triglycerides.



Progesterone,
cholesterol.

the

pregnancy

hormone,

raises

Not all of these effects are necessarily bad, nor are
they necessarily even significant. For instance, estrogen is clearly beneficial. Each effect must be considered in the overall goal of treatment.

Causes and symptoms
A combination of heredity and diet is responsible
for the majority of fat disorders. It is not so much the
cholesterol in the diet that is the problem, because that
accounts for only 10% of the body’s store. It is the
other fats in the diet that alter the way the body
handles its cholesterol. There is a convincing relation
between fats in the diet and the incidence of atherosclerosis. The guilty fats are mostly the animal fats, but
palm and coconut oil also are harmful. These fats are
called saturated fats for the chemical reason that most
of their carbon atoms have as many hydrogen atoms
attached as they can accommodate. More important
than the kind of fat is the amount of fat. For many
people, fat is half of their diet. One-fifth to one-fourth
is a much healthier fraction, the rest of the diet being
made up of complex carbohydrates and protein.
This disease is silent for decades, until the first
episode of heart disease or stroke.

Diagnosis
It would be easier if simple cholesterol and triglyceride tests were all it took to assess the risk of atherosclerosis. But the important information is which package
the cholesterol is in—the LDLs or the HDLs. That
takes a more elaborate testing process. To complicate
matters further, the amount of fats in the blood varies
greatly in relation to the last meal—how long ago it was
and what kind of food was eaten. A true estimate of the
risk comes from several tests several weeks apart, each
done after at least twelve hours of fasting.

Treatment
Diet and lifestyle change are the primary focus for
most cholesterol problems. It is a mistake to think that
a pill will reverse the effects of a bad diet, obesity,
smoking, excess alcohol, stress, and inactivity.
Reducing the amount of fat in the diet by at least
GALE ENCYCLOPEDIA OF MEDICINE

half is the most important move to make. Much of
the food eaten to satisfy a ‘‘sweet tooth’’ is higher in fat
than in sugar. A switch away from saturated fats is the
next step, but the rush to polyunsaturated fats was illconceived. These, particularly the hydrogenated fats
in margarine, have problems of their own. They raise
the risk of cancer and are considered more dangerous
than animal fat by many experts. Theory supports
population studies that suggest monounsaturated
olive oil may be the healthiest of all.
There was a tremendous push at the end of the
20th century to use lipid-lowering medications. The
most popular and most expensive agents, the ‘‘statins,’’ hinder the body’s production of cholesterol
and sometimes damage the liver as a side effect.
Their full name is 3-hydroxy-3-methylglutarylcoemzyme A (HMG-CoA) reductase inhibitors. Their
generic names are cervistatin, fluvastatin, lovastatin,
pravastatin, simvastatin, and the newest and most
powerful to date, rosuvastatin. Studies show that
these drugs lower cholesterol. Only recently, though,
has any evidence appeared that this affects health and
longevity. Earlier studies showed, in fact, an increased
death rate among users of the first class of lipidaltering agents—the fibric acid derivatives. The chain
of events connecting raised HDL and lowered LDL
cholesterol to longer, healthier lives is still to be
forged.
High-tech methods of rapidly reducing very high
blood fat levels are performed for those rare disorders
that require it. There are resins that bind cholesterol in
the intestines. They taste awful, feel like glue and
routinely cause gas, bloating, and constipation. For
acute cases, there is a filtering system that takes fats
directly out of the blood.
Niacin (nicotinic acid) lowers cholesterol effectively and was the first medication proven to improve
overall life expectancy. It also can be liver toxic, and
the usual formulation causes a hot flash in many
people. This can be overcome by taking a couple of
aspirins 30 minutes before the niacin, or by taking a
special preparation called ‘‘flush free,’’ ‘‘inositolbound’’ or inositol hexanicotinate.

Alternative treatment
Omega-3 oil is a special kind found mostly in
certain kinds of fish. It is beneficial in lowering
cholesterol. An herbal alternative called guggulipid,
Commiphora mukul, an extract of an Indian plant,
has been touted as working the same way as the expensive and liver toxic cholesterol-lowering medications.
However, a 2003 clinical trial found that the
1889

Hyperlipoproteinemia



Hypernatremia

KEY TERMS
Atherosclerosis—Hardening of the arteries due to
fat (cholesterol) deposits in their walls. Also known
as arteriosclerosis.
Genetic—Refers to the genes and characteristics
inherited from parents.
Inflammation—The body’s response to irritation,
by releasing chemicals that attack germs and tissues
and also repair the damage done.
Lesion—Localized disease or damage.
Pancreatitis—Inflammation of the pancreas.
Serum—The liquid part of blood, from which all
the cells have been removed.

supplement did not meet these claims. In fact, guggul
did not lower total cholesterol, LDL cholesterol, or
triglycerides. Most patients tolerated the supplement,
but some developed a hypersensitivity rash.
To lower cholesterol, naturopathic medicine, traditional Chinese medicine, and ayurvedic medicine may
be considered. Some herbal therapies include alfalfa
(Medicago sativa), Asian ginseng (Panax ginseng), and
fenugreek (Trigonella foenum-graecum). Garlic
(Allium sativum) and onions are also reported to
have cholesterol-lowering effects. In naturopathic
medicine, the liver is considered to be an organ that
needs cleansing and rebalancing. The liver often is
treated with a botanical formula that will act as a bitter
to stimulate bile flow in the liver. Before initiating
alternative therapies, medical consultation is strongly
advised.

assessed. The sooner any problems are identified, the
better the chances of limiting or preventing the associated health risks. Anyone with a family history of
disorders leading to hyperlipoproteinemia also may
benefit from genetic testing and counseling to assist
them in making reproductive decisions.
Resources
PERIODICALS

Brunk, Doug. ‘‘Three Studies Further Confirm Ill Effects of
HRT: Heart Disease Risk Rises First Year of Use:
Continuing Analysis of WHI Data.’’ Family Practice
News 33, no. 17 (September 1, 2003): 1–2.
Dowhower Karpa, Kelly. ‘‘New Statin Said to be More
Powerful than Others.’’ Drug Topics 147, no. 17
(September 1, 2003): 27.
‘‘Herbal Extract Not Effective in Treating High
Cholesterol.’’ Drug Week August 29, 2003: 197.
Kyperos, Kyriakos E., et al. ‘‘Molecular Mechanisms of
Type III Hyperlipoproteinemia: the Contribution of the
Carboxy-terminal Domain of ApoE Can Account for
the Dyslipidemia that is Associated With the E2/E2
Phenotype.’’ Biochemistry 42, no. 33 (August 26, 2003):
9841–9853.
ORGANIZATIONS

Inherited High Cholesterol Foundation. 410 Chipeta Way,
Room 167, Salt Lake City, UT 84104. (888) 244-2465.

J. Ricker Polsdorfer, MD
Teresa G. Odle

Hypermagnesemia see Magnesium
imbalance
Hypermenorrhea see Dysfunctional uterine
bleeding
Hypermetropia see Hyperopia

Prognosis
The prognosis is good for Type 1 hyperlipoproteinemia with treatment; without treatment, death
may result. For Type 2 the prognosis is poor even
with treatment. The prognosis for type 3 is good when
the prescribed diet is strictly followed. For types 4 and 5
the prognosis is uncertain, due to the risk of developing
premature coronary artery disease and pancreatitis,
respectively.

Prevention
Genetic inheritance cannot be changed, but its
effects may be modified with proper treatment.
Family members of an individual with hyperlipoproteinemia should consider having their blood lipids
1890

Hypernatremia
Definition
The normal concentration of sodium in the blood
plasma is 136–145 mM. Hypernatremia is defined as a
serum sodium level over 145 mM. Severe hypernatremia, with serum sodium above 152 mM, can result in
seizures and death.

Description
Sodium is an atom, or ion, that carries a single
positive charge. The sodium ion may be abbreviated
GALE ENCYCLOPEDIA OF MEDICINE

About 40% of the body’s sodium is contained in
bone. Approximately 2–5% occurs within organs and
cells and the remaining 55% is in blood plasma and
other extracellular fluids. The amount of sodium in
blood plasma is typically 140 mM, a much higher
amount than is found in intracellular sodium (about
5 mM). This asymmetric distribution of sodium ions is
essential for human life. It makes possible proper
nerve conduction, the passage of various nutrients
into cells, and the maintenance of blood pressure.
The body continually regulates its handling of
sodium. When dietary sodium is too high or low, the
intestines and kidneys respond to adjust concentrations to normal. During the course of a day, the intestines absorb dietary sodium while the kidneys excrete a
nearly equal amount of sodium into the urine. If a low
sodium diet is consumed, the intestines increase their
efficiency of sodium absorption, and the kidneys
reduce its release into urine.
The concentration of sodium in the blood plasma
depends on two things: the total amount of sodium
and water in arteries, veins, and capillaries (the circulatory system). The body uses separate mechanisms to
regulate sodium and water, but they work together to
correct blood pressure when it is too high or too low.
Too high a concentration of sodium, or hypernatremia, can be corrected either by decreasing sodium or
by increasing body water. The existence of separate
mechanisms that regulate sodium concentration
account for the fact that there are numerous diseases
that can cause hypernatremia, including diseases of
the kidney, pituitary gland, and hypothalamus.

Causes and symptoms
Vasopressin, also called anti-diuretic hormone,
is made by the hypothalamus and released by the pituitary gland into the bloodstream. There it travels to the
kidney where it reduces the release of water into the
urine. With less vasopressin production, the body fails
to conserve water, and the result is a trend toward
higher plasma sodium concentrations. Hypernatremia
may occur in diabetes insipidus, a disease that causes
excessive urine production. (It is not the same disease
as diabetes mellitus, a disease resulting from impaired
insulin production.) The defect involves either the
GALE ENCYCLOPEDIA OF MEDICINE

failure of the hypothalamus to make vasopressin or
the failure of the kidney to respond to vasopressin. In
either case, the kidney is able to conserve and regulate
the body’s sodium levels, but is unable to conserve
and retain the body’s water. Hypernatremia does
not occur in diabetes insipidus if the patient is able to
drink enough water to keep up with urinary loss,
which may be as high as 10 liters per day.
Hypernatremia may occur in unconscious (or
comatose) patients due to the inability to drink
water. Water is continually lost by evaporation from
the lungs and in the urine. If the patient is not given
water via infusion, the sodium concentration in the
blood may increase and hypernatremia could develop.
Hypernatremia can also occur in rare diseases in which
the thirst impulse is impaired.
Hypernatremia can also occur accidentally in the
hospital when patients are infused with solutions containing sodium, such as sodium bicarbonate for the
treatment of acidosis (acidic blood). It can also be
accidentally induced with sodium chloride infusions,
especially in elderly patients with impaired kidney
function.
Hypernatremia can cause neurological damage
due to shrinkage of brain cells. Neurological symptoms include confusion, coma, paralysis of the lung
muscles, and death. The severity of the symptoms is
related to how rapidly the hypernatremia developed.
Hypernatremia that comes on rapidly does not allow
the cells of the brain time to adapt to their new highsodium environment. Hypernatremia is especially
dangerous for children and the elderly.

Diagnosis
Hypernatremia is diagnosed by acquiring a blood
sample, preparing plasma, and using a sodium-sensitive electrode for measuring the concentration of
sodium ions.

Treatment
Hypernatremia is treated with infusions of a solution of water containing 0.9% sodium chloride (0.9
grams NaCl/100 ml water), which is the normal concentration of sodium chloride in the blood plasma.
The infusion is performed over many hours or days
to prevent abrupt and dangerous changes in brain cell
volume. In emergencies, such as when hypernatremia
is causing neurological symptoms, infusions may be
conducted with salt solutions containing 0.45%
sodium chloride, which is half the normal physiologic
level.
1891

Hypernatremia

as Na+ or as simply Na. Sodium can occur as a salt in a
crystalline solid. Sodium chloride (NaCl), sodium phosphate (Na2HPO4) and sodium bicarbonate (NaHCO3)
are commonly occurring salts. These salts can be dissolved in water or in juices of various foods. Dissolving
involves the complete separation of ions, such as
sodium and chloride in common table salt (NaCl).

Hyperopia

KEY TERMS
Blood plasma and serum—Blood plasma, or
plasma, is prepared by obtaining a sample of
blood and removing the blood cells. The red
blood cells and white blood cells are removed by
spinning with a centrifuge. Chemicals are added to
prevent the blood’s natural tendency clot. If these
chemicals include sodium, then a false measurement of plasma sodium content will result. Serum is
prepared by obtaining a blood sample, allowing
formation of the blood clot, and removing the clot
using a centrifuge. Both plasma and serum are light
yellow in color.

Prognosis
The prognosis for treating hypernatremia is excellent, except if neurological symptoms are severe or if
overly rapid attempts are made to treat and reverse the
condition.

Prevention
Hypernatremia occurs only in unusual circumstances that are not normally under a person’s control.
Resources
PERIODICALS

Fried, L. F., and P. M. Palevsky. ‘‘Hyponatremia and
hypernatremia.’’ Medical Clinics of North America 81
(1997): 585-609.

the dense material is not perpendicular to the incoming
light, as is the case with the curved surfaces on lenses
and corneas, the direction of the light changes. The
greater the curvature of the lens system, the greater
the change in the direction of the light.
When parallel light rays from an object go
through the lens system of the eye, they are bent so
they converge at a point some distance behind the lens.
With perfect vision this point of convergence, where
the light rays are focused, is on the retina. This happens when the cumulative curvature of the lens plus
cornea and the distance from the lens to the retina are
just right for each other. The condition where the
point of focus of parallel light rays from an object is
behind the retina is called hyperopia. This condition
exists when the combined curvature of the lens and
cornea is insufficient (e.g., flatter than needed for the
length of the eyeball). This condition can be equivalently described by saying hyperopia exists when the
eyeball is too short for the curvature of its lens system.
There is a connection between the focusing of the
lens of the eye (accommodation) and convergence of
the eyes (the two eyes turning in to point at a close
object). The best example is during reading. The lens
accommodates to make the close-up material clear
and the eyes turn in to look at the print and keep it
single. Because of this connection between accommodation and convergence, if the lens needs to accommodate to focus for distance (to bring the image back
onto the retina) the eyes may appear to turn in even
when looking at the distance. This can cause a condition known as accommodative esotropia in children.
The eyes turn in and the cause is accommodation
because of hyperopia.

Tom Brody, PhD

Hypernephroma see Kidney cancer

Hyperopia
Definition
Hyperopia (farsightedness) is the condition of the
eye where incoming rays of light reach the retina
before they converge into a focused image.

Description
When light goes through transparent but dense
material like the materials of the eye’s lens system (the
lens and cornea), its velocity decreases. If the surface of
1892

Causes and symptoms
Babies are generally born slightly hyperopic. This
tends to decrease with age. There is normal variation
in eyeball length and curvature of the lens and cornea.
Some combinations of these variables give rise to eyes
where the cornea is too flat for the distance between
the cornea and the retina. If the hyperopia is not too
severe the lens may be able to accommodate and bring
the image back onto the retina. This would result in
clear distance vision, but the constant focusing might
result in headaches or eyestrain. If the lens cannot
accommodate for the full amount of the hyperopia
the distance image would be blurry.
If the eyes are focusing for distance and now the
person is looking at a near object, the eyes need to
accommodate further. This may result in blurry near
objects or headaches during near work.
GALE ENCYCLOPEDIA OF MEDICINE

Hyperopia

Retina
Cornea

Light

Light
Lens

Normal eye

Hyperopia (farsightedness)

Hyperopia, or farsightedness, is a condition of the eye where incoming rays of light impinge on the retina before converging into
a focused image, resulting in difficulty seeing nearby objects clearly. (Illustration by Electronic Illustrators Group.)

Depending upon the amount of hyperopia, symptoms can range from none to clear distance vision but
blurry near vision, to blurry distance and near vision.
Headaches and eyestrain may also occur, particularly
when doing near tasks. An eye turned in (esotropia)
may be a result of hyperopia, particularly in children.
However, because a turned eye may be a result of
more serious causes it is very important to have it
checked out.

Diagnosis
Because it is possible to have good visual acuity
with some degree of hyperopia it is important to relax
accommodation before the eye exam. This is done
with the use of eyedrops and is called a cycloplegic
exam or cycloplegic refraction. The drops relax the
accommodation (thus making reading blurry until
the drops wear off). Patients will usually be asked to
have someone drive them home because of the blurriness. The doctor can then determine the patient’s
visual status with a hand-held instrument called a
retinoscope and/or have the patient read from an eye
chart while placing different lenses in front of the
patient’s eyes. Refractive error is measured in units
called diopters (D).

Treatment
The usual treatment for hyperopia is corrective
lenses (spectacles or contact lenses).
Different surgical methods to correct hyperopia
are under investigation. One approach is to implant
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cornea—The clear, dome-shaped outer covering
of the front of the eye. It lies in front of the iris and
pupil.
Iris—The colored ring just behind the cornea and
in front of the lens that controls the amount of light
sent to the retina.
Pupil—The black hole in the center of the iris. Light
enters here on the way to the lens and retina.
Refraction—Method of determining the optical
status of the eyes. Lenses are placed before the
patient’s eyes while reading from an eye chart. The
result is the eyeglass or contact lens prescription.
Retina—The inner, light-sensitive layer of the eye
containing rods and cones; transforms the image it
receives into electrical messages sent to the brain
via the optic nerve.

corrective contact lenses behind the patient’s iris. The
first experimental implantable contact lenses were
implanted in 1997. Another approach is to surgically
increase the curvature of the eye’s existing cornea or
lens. Although there have been many reports of success using different kinds of lasers to increase corneal
curvature, as of 1998 there are still problems with
stability and predictability. The introduction of
light-activated biologic tissue glue in 1997 holds promise for improvements in those areas.
1893

Hyperparathyroidism

Prognosis
The prognosis for fully corrected vision is excellent for patients with low to moderate amounts of
hyperopia. Patients with very high hyperopia
(+10.00D or more) may not achieve full correction.
Moreover, surgery to correct hyperopia will probably
be perfected and approved in the near future.
Hyperopia increases the chances of chronic glaucoma, but vision loss from glaucoma is preventable.

Prevention
Hyperopia is usually present at birth, and there is
no known way to prevent it.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
PO Box 7424, San Francisco, CA 94120-7424. <http://
www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
OTHER

Edmiston, Dave. ‘‘Hyperopia.’’ Lasikpatient.org. <http://
www.lasikpatient.org>.

Lorraine Lica, PhD

Hyperparathyroidism
Definition
Parathyroid glands are four pea-sized glands
located just behind the thyroid gland in the front
of the neck. The function of parathyroid glands is
to produce a hormone called parathyroid hormone
(parathormone), which helps regulate calcium and
phosphate in the body. Hyperparathyroidism is the
overproduction of this hormone.

Description
Thyroid glands and parathyroid glands, despite
their similar name and proximity, are entirely separate, and each produces hormones with different functions. Hyperparathyroidism may be primary or
secondary. It most often occurs in those over age 30,
and most commonly in patients 50 to 60 years old. It
rarely occurs in children or the elderly. Women are
1894

affected by the disease up to three times more often
than men. It is estimated that 28 of every 100,000
people in the United States will develop hyperparathyroidism each year.
Normally, parathyroid glands produce the parathormone as calcium levels drop and lower to meet the
demands of a growing skeleton, pregnancy, or lactation. However, when one or more parathyroid glands
malfunctions, it can lead to overproduction of the
hormone and elevated calcium level in the blood.
Therefore, a common result of hyperparathyroidism
is hypercalcemia, or an abnormally high level of calcium in the blood. Primary hyperparathyroidism
occurs as a malfunction of one of the glands, usually
as a result of a benign tumor, called adenoma.
Secondary hyperparathyroidism occurs as the result
of a metabolic abnormality outside the parathyroid
glands, which causes a resistance to the function of
the parathyroid hormones. Primary hyperparathyroidism is one of the most common endocrine disorders, led only by diabetes and hyperthyroidism.

Causes and symptoms
Often, there are no obvious symptoms or suspicion of hyperparathyroidism, and it is first diagnosed
when a patient is discovered to be hypercalcemic
during a routine blood chemistry profile. Patients
may believe they have felt fine, but realize improvements in sleep, irritability, and memory following
treatment. When symptoms are present, they may
include development of gastric ulcers or pancreatitis
because high calcium levels can cause inflammation
and pain in the linings of the stomach and pancreas.
Most of the symptoms of hyperparathyroidism
are those present as a result of hypercalcemia, such
as kidney stones, osteoporosis, or bone degradation
resulting from the bones giving up calcium. Muscle
weakness, central nervous system disturbances such
as depression, psychomotor and personality disturbances, and rarely, even coma can occur. Patients
may also experience heartburn, nausea, constipation,
or abdominal pain. In secondary hyperparathyroidism, patients may show signs of calcium imbalance
such as deformities of the long bones. Symptoms of
the underlying disease may also be present.
Most commonly, hyperparathyroidism occurs as
the result of a single adenoma, or benign tumor, in one
of the parathyroid glands. About 90% of all cases of
hyperparathyroidism are caused by an adenoma. The
tumors are seldom cancerous. They will grow to a
much larger size than the parathyroid glands, often
to the size of a walnut. Genetic disorders or multiple
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Diagnosis of hyperparathyroidism is most often
made when a blood test (radioimmunoassay) reveals
high levels of parathyroid hormone and calcium.
A blood test that specifically measures the amount
of parathyroid hormone has made diagnosis simpler.
X-ray examinations may be performed to look for
areas of diffuse bone demineralization, bone cysts,
outer bone absorption and erosion of the long bones
of the fingers and toes. Hypercalcemia is mild or
intermittent in some patients, but is an excellent
indicator of primary hyperparathyroidism. Dual
energy x-ray absorptiometry (DEXA or DXA), a
tool used to diagnose and measure osteoporosis, is
used to show reduction in bone mass for primary
hyperparathryroidism patients. Once a diagnosis of
hyperparathyroidism is reached, the physician will
probably order further tests to evaluate complications. For example, abdominal radiographs might
reveal kidney stones.
For secondary hyperparathyroidism, normal
or slightly decreased calcium levels in the blood
and variable phosphorous levels may be visible.
Patient history of familial kidney disease or convulsive
disorders may suggest a diagnosis of secondary
hyperparathyroidism. Other tests may reveal a disease
or disorder, which is causing the secondary
hyperparathyroidism.

Treatment
Hyperparathyroidism cases will usually be referred
to an endocrinologist, a physician specializing in hormonal problems, or a nephrologist, who specializes in
kidney and mineral disorders.
Patients with mild cases of hyperparathyroidism
may not need immediate treatment if they have
only slight elevations in blood calcium level and
normal kidneys and bones. These patients should be
regularly checked, probably as often as every six
months, by physical examination and measurement
of kidney function and calcium levels. A bone densitometry measurement should be performed every one
or two years. After several years with no worsened
symptoms, the length of time between exams may be
increased.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Demineralization—A loss or decrease of minerals
in the bones.
Endocrine—Glands and hormone secretions in the
body circulation.
Phosphate—An organic compound necessary for
mineralization of bone and other key cellular
processes.

Patients with more advanced hyperparathyroidism will usually have all or half of the affected parathyroid gland or glands surgically removed. This
surgery is relatively safe and effective. The primary
risks are those associated with general anesthesia.
There are some instances when the surgery can
be performed with the patient under regional, or
cervical block, anesthesia. Often studies such as
ultrasonography prior to surgery help pinpoint the
affected areas.

Alternative treatment
Forcing fluids and reducing intake of calcium-rich
foods can help decrease calcium levels prior to surgery
or if surgery is not necessary.

Prognosis
Removal of the enlarged parathyroid gland or
glands cures the disease 95% of the time and relief of
bone pain may occur in as few as three days. In up to
5% of patients undergoing surgery, chronically low
calcium levels may result, and these patients will
require calcium supplement or vitamin D treatment.
Damage to the kidneys as a result of hyperparathyroidism is often irreversible. Prognosis is generally
good, however complications of hyperparathyroidism
such as osteoporosis, bone fractures, kidney stones,
peptic ulcers, pancreatitis, and nervous system difficulties may worsen prognosis.

Prevention
Secondary hyperparathyroidism may be prevented by early treatment of the disease causing it.
Early recognition and treatment of hyperparathyroidism may prevent hypercalcemia. Since the cause of
primary hyperparathyroidism, or the adenoma which
causes parathyroid enlargement, is largely unknown,
there are not prescribed prevention methods.
1895

Hyperparathyroidism

endocrine tumors can also cause a parathyroid gland
to enlarge and oversecrete hormone. In 10% or fewer
of patients with primary hyperparathyroidism, there
is enlargement of all four parathyroid glands. This
condition is called parathyroid hyperplasia.

Hyperpigmentation

Resources
ORGANIZATIONS

Osteoporosis and Related Bone Diseases—National
Resource Center. 1150 17th S. NW, Ste. 500,
Washington, DC 20036. (800) 624-2663.
Paget Foundation. 200 Varick St., Ste. 1004. New York, NY
10014-4810. (800) 23-PAGET.
OTHER

‘‘Endocrine Disorder and Endocrine Surgery.’’ Endocrine
Web Page. <http://www.endocrineweb.com>.

Teresa Odle

Hyperpigmentation
Definition
Hyperpigmentation is the increase in the natural
color of the skin.

Description
Melanin, a brown pigment manufactured by
certain cells in the skin called melanocytes, is responsible for skin color. Melanin production is stimulated
by a pituitary hormone called melanocyte stimulating
hormone (MSH). Other pigments appear in the skin
much less often.

Causes and symptoms
Darkened spots on the skin come in several varieties. The most ominous is malignant melanoma, a
very aggressive cancer that begins as an innocent
mole. The majority of moles (nevus), however, are and
remain benign (harmless). The average person has several dozen, and certain people with a hereditary excess
may have hundreds. Freckles, age spots, and cafe au
lait spots, known as ephelides, are always flat and not
as dark. Cafe au lait spots are seen mostly in people
with another hereditary disorder called neurofibromatosis. ‘‘Port wine stains’’ are congenital dark red
blotches on the skin. Other common dark colorations
on the skin are called keratosis and consist of locally
overgrown layers of skin that are dark primarily
because there is more tissue than normal. A few of
these turn into skin cancers of a much less dangerous
kind than melanoma.
Darkened regions of the skin occur as a result of
abnormal tanning when the skin is sensitive to
1896

sunlight. Several diseases and many drugs can
cause photosensitivity. Among the common drugs
responsible for this uncommon reaction are birth
control pills, antibiotics (sulfonamides and tetracyclines), diuretics, nonsteroidal anti-inflammatory
drugs (NSAID), pain relievers, and some psychoactive medications. Some of the same drugs may also
cause patches of discolored skin known as localized
drug reactions and representing an allergy to that
drug. Sunlight darkens an abnormal chemical in the
skin of patients with porphyria cutanea tarda.
Several endocrine diseases, some cancers, and
several drugs abnormally stimulate melanocytes,
usually through an overproduction of MSH. Arsenic
poisoning and Addison’s disease are among these
causes. A condition known as acanthosis nigricans is
a velvety darkening of skin in folded areas (arm pits,
groin, and neck) that can signal a cancer or hormone
imbalance.
Of particular note is a condition called melasma
(dark pigmentation of the skin), caused by the female
hormone estrogen. Normal in pregnancy, this brownish discoloration of the face can also happen with birth
control pills that contain estrogen.
Overall darkening of the skin may be due to pigmented chemicals in the skin. Silver, gold, and iron
each have a characteristic color when visible in the
skin. Several drugs and body chemicals, like bilirubin,
can end up as deposits in the skin and discolor it.
There are a number of other rare entities that
color the skin, each in its own peculiar way. Among
these are strange syndromes that seem to be birth
defects and vitamin and nutritional deficiencies.

Diagnosis
The pattern of discoloration is immediately
visible to the trained dermatologist, a physician
specializing in skin diseases, and may be all that is
required to name and characterize the discoloration.
Many of these pigment changes are signs of internal
disease that must be identified. Pigmentation
changes may also be caused by medication, and the
drug responsible for the reaction must be identified
and removed.

Treatment
Skin sensitive to sunlight must be protected by
shade or sunscreens with an SPF of 15 or greater.
Skin cancers must be, and unsightly benign lesions
may be, surgically removed. Laser surgery is an effective removal technique for many localized lesions.
GALE ENCYCLOPEDIA OF MEDICINE

Addison’s disease—A degenerative disease that is
characterized by weight loss, low blood pressure,
extreme weakness, and dark brown pigmentation
of the skin.
Dermatologist—A physician specializing in the
study of skin conditions and diseases
Diuretic—A cause of increased urine flow.
Keratosis—A skin disease characterized by an overgrowth of skin, which usually appears discolored.
Lesion—Any localized abnormality.
Melasma—Dark pigmentation of the skin.
Neurofibromatosis—Otherwise known as von
Recklinghausen’s disease, consists of pigmented
skin spots and numerous soft tumors all over the
body.
Nevus—Birthmark or mole.
NSAID—Nonsteroidal anti-inflammatory drugs—
aspirin, ibuprofen, naproxen, and many others.
Porphyria cutanea tarda—An inherited disease
that results in the overproduction of porphyrins.
Syndrome—Common features of a disease or
features that appear together often enough to suggest
they may represent a single, as yet unknown, disease entity.

Because it spreads so rapidly, melanoma should be
immediately removed, as well as some of the surrounding tissue to prevent regrowth.

Prevention

Hypersensitivity pneumonitis
Definition
Hypersensitivity pneumonitis refers to an inflammation of the lungs caused by repeated breathing in of
a foreign substance, such an organic dust, a fungus, or
a mold. The body’s immune system reacts to these
substances, called antigens, by forming antibodies,
molecules that attack the invading antigen and try
to destroy it. The combination of antigen and antibody produces acute inflammation, or pneumonitis
(a hypersensitivity reaction), which later can develop
into chronic lung disease that impairs the lungs’ ability
to take oxygen from the air and eliminate carbon
dioxide.

Description
Hypersensitivity pneumonitis (HP) is sometimes
called ‘‘allergic alveolitis.’’ ‘‘Allergic’’ refers to the antigen-antibody reaction, and ‘‘alveolitis’’ means an
inflammation of the tiny air sacs in the lungs where
oxygen and CO2 are exchanged, the alveoli. It also is
known as ‘‘extrinsic’’ allergic alveolitis, meaning that
the antigen that sets up the allergic reaction (also called
an allergen) comes from the outside. Most of the antigens that cause this disease come from plant or animal
proteins or microorganisms, and many of those affected
are exposed either at work or in the course of some
hobby or other activity. The first known type of HP,
farmer’s lung, is caused by antigens from tiny microorganisms living on moldy hay. An example of disease
connected with a hobby is pigeon breeder’s lung, caused
by inhaling protein material from bird droppings or
feathers. After a time, very little of the allergenic material is needed to set off a reaction in the lungs.

Hyperprolactation see Galactorrhea

Roughly one in every 10,000 persons develops
some form of HP. A mysterious aspect of this condition is that, even though many persons may be
exposed to a particular antigen, only a small number
of them will develop the disease. Genetic differences
may determine who becomes ill; this remains unclear.
Probably between 5% and 15% of all persons who are
regularly exposed to organic materials develop HP.
Most of those who do get it do not smoke (smoking
may create the type of cells that take up antigens
and neutralize them). The amount of antigen is an
important factor in whether HP will develop and
what form it will take. Sudden heavy exposure can
produce symptoms in a matter of hours, whereas
mild but frequent exposures tend to produce a longlasting, ‘‘smoldering’’ illness. HP may be more likely

GALE ENCYCLOPEDIA OF MEDICINE

1897

Sunlight is the leading cause of dark spots on the
skin, so shade and sunscreens are necessary preventive
strategies, especially in people who burn easily.
Resources
PERIODICALS

Bernstein L. J., et al. ‘‘The Short- and Long-term Side
Effects of Carbon Dioxide Laser Resurfacing.’’
Dermatologic Surgery 23 (July 1997): 519-525.

J. Ricker Polsdorfer, MD

Hypersensitivity pneumonitis

KEY TERMS

Hypersensitivity pneumonitis

to develop in persons exposed to polluted air or industrial fumes.
Typical changes occur in the lungs of persons with
HP. In the acute stage, large numbers of inflammatory
cells are found throughout the lungs and the air sacs
may be filled by a thick fluid mixed with these cells. In
the subacute stage, disease extends into the small
breathing tubes, or bronchioles, and the inflammatory
cells collect into tiny granules called granulomas.
Finally, in the chronic stage of HP, the previously
inflamed parts of the lungs become scarred and unable
to function, as in pulmonary fibrosis.

Causes and symptoms
A number of different types of HP are known,
since a wide range of allergens may produce an allergic
reaction in the lungs. Many of them produce similar
symptoms and abnormal physical findings, but some
have their own typical features. Some of the more
common forms are:


Farmer’s lung. Can affect any farmer who works
with wet hay or other moldy dust. Small farmers
who have to directly thresh and handle their hay
are most at risk, as are those living in cold and
humid areas where damp weather is common.



Pigeon breeder’s lung. Also called ‘‘bird fancier’s
lung,’’ it is second to farmer’s lung as the best known
type of HP. A substance has been found in pigeon
droppings that may cause the allergic reaction, but
there may be more than one such substance. Besides
pigeons, the disorder may follow exposure to ducks,
geese, pheasants, and even canaries. Parakeets produce an especially severe form of disease. Most
patients are middle-aged women, who usually care
for birds either at home or on bird breeding farms.



Bagassosis. Caused by bagasse, a substance produced when juice is extracted from sugar cane and
is used in making paper and explosives. A fungus is
probably responsible. Young and middle-aged men
who work in the sugar industry are at risk.



Byssinosis. A similar condition affecting workers
who inhale dust from cotton, flax, or hemp.



Humidifier lung. An acute form of HP caused by
inhaling actinomycyetes, the same organisms that
cause farmer’s lung, which grow in contaminated
humidifier vents, air conditioners, heating systems,
and even saunas.



Other antigens. HP has been seen in persons working
with detergents, silicone, mushrooms, cheese, wood
dust, maple bark, coffee, and furs.

1898

In the acute stage, patients with HP begin coughing, develop fever, and note tightness in the chest as
well as extreme tiredness and aching, four to eight
hours after the most recent exposure. Most patients
are well aware of the connection between their work
(or an activity) and their symptoms. After a time,
patients may have trouble breathing. They also may
lose their appetite, lose weight, and generally feel ill.
Finally, in the chronic stage, the patient will have
increasing trouble breathing and may sometimes
wheeze. With advanced disease, the skin may appear
bluish (because too little oxygen is getting into the
blood). When the physician listens to the patient’s
chest with a stethoscope, there may be crackling
sounds or loud wheezing. In the late stages, clubshaped fingertips are a sign that the patient has
not been getting enough oxygen for an extended
period of time.

Diagnosis
No single test can make a definite diagnosis of HP.
The key is to relate some specific exposure or activity
to episodes of symptoms. The chest x ray may be
normal in the acute stage, but later may show a hazy
appearance that looks like ‘‘ground glass.’’ There may
be linear or rounded shadows in the central parts of
the lungs. Studies of lung function in the acute stage
typically show abnormally small lung volume. The
ability to breathe at a fast rate is impaired. Blood
from an artery typically has a low level of oxygen.
Later, when the lungs have begun to scar, the airways
(breathing tubes) are obstructed and the rate of air
flow is reduced.
Some experts believe that skin testing can help
diagnose HP and show which particular antigen is
causing the symptoms. Small amounts of several
suspect antigens are injected just beneath the surface
of the skin, usually on the arm or back, and the reactions compared to that caused by injecting a harmless salt solution. Another diagnostic test is to place a
thin tube into the airways, inject a small amount of
fluid, and draw it back up (bronchoalveolar lavage).
A very large number of cells called lymphocytes is
typical of HP, and mast cells, which are part of the
immune system, may also be seen. Rarely, a tissue
sample (biopsy) of lung tissue may be taken through
a tube placed in the airways and examined under
a microscope. Finally, a patient may be ‘‘challenged’’
by actually inhaling a particular antigen in the
form of an aerosol and noting whether lung function
suddenly becomes worse. This test is usually not
necessary.
GALE ENCYCLOPEDIA OF MEDICINE

Allergen—An outside substance, such as dust or a
mold, that, when inhaled, sets off an allregic
(hypersensitivity) reaction in the lungs.
Fibrosis—A result of long-standing inflammatory
disease in which normal tissue is replaced by scar
tissue that is functionally useless.
Granuloma—A collection of inflammatory cells
forming a microscopic lesion, many of which are
scattered throughout the lung tissue in patients who
have had numerous acute episodes of HP.
Hypersensitivity—After the body’s immune system
attacks an outside invader (such as organic dust or a
fungus) many times, exposure to even a tiny amount
of this allergen can provoke a strong inflammatory
response.
Pneumonitis—Inflammation of the lung tissues.
Steroid—A natural body substance may be given
orally or by injection, and serves to dampen or even
halt inflammation anywhere in the body, including
the lungs.

Treatment
Treatment of HP requires identifying the offending antigen and avoiding further exposure. Although
it may sometimes be necessary for a patient to find a
totally different type of work, often it is possible to
simply perform different duties or switch to a work site
where exposure is minimal. In some cases, (like pigeon
breeder’s lung), wearing a mask can prevent exposure.
If acute symptoms are severe, the patient may be
treated with a steroid hormone for two to six weeks.
This often suppresses the inflammatory response and
allows the lungs a chance to recover. In the chronic
stage, steroid treatment can delay further damage to
the lungs and help preserve their function.

then unable to properly provide oxygen to the blood.
Rarely, a patient will become permanently disabled.

Prevention
It is often not possible to prevent initial episodes
of HP, because there is no way of predicting which
individuals (such as farmers) will have an allergic reaction to a particular allergen. Once the connection is
made between a type of exposure and definite hypersensitivity symptoms, prevention of further episodes is
simple as long as further exposure can be avoided.
Exactly how to avoid exposure depends on a person’s work or activities and what he or she is reacting to.
People with farmer’s lung can dry hay thoroughly
before storing it. For pigeon breeder’s lung (and many
other types of HP), a mask can be worn. In many
industrial settings, it is possible to take precautions
that will limit the amount of allergen that workers will
inhale. If it is not possible to avoid exposure altogether,
exposure can be timed and strictly minimized.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York, NY
10019. (800) 586-4872. <http://www.lungusa.org>.
Asthma and Allergy Foundation of America. 1233 20th
Street, NW, Suite 402, Washington, DC 20036. (800)
727-8462. <http://www.aafa.org>.

David A. Cramer, MD

Hypersomnia see Sleep disorders

Hypersplenism
Definition
Hypersplenism is a type of disorder which causes
the spleen to rapidly and prematurely destroy blood
cells.

Prognosis
In general, most of the symptoms of HP disappear
when the patient is no longer exposed to the causative
allergen. The actual chances of complete recovery
depend in part on what form of HP is present. Older
patients and those exposed repeatedly for long periods
after initially developing symptoms tend to have a poorer
long-term outlook. The worst outcome is that long
repeated episodes of exposure will cause chronic lung
inflammation, scar the lungs, and permanently make
GALE ENCYCLOPEDIA OF MEDICINE

Description
The spleen is located in the upper left area of the
abdomen. One of this organ’s major functions is to
remove blood cells from the body’s bloodstream. In
hypersplenism, its normal function accelerates, and it
begins to automatically remove cells that may still be
normal in function. Sometimes, the spleen will temporarily hold onto up to 90% of the body’s platelets
and 45% of the red blood cells. Hypersplenism may
1899

Hypersplenism

KEY TERMS

Hypersplenism

occur as a primary disease, leading to other complications, or as a secondary disease, resulting from an
underlying disease or disorder. Hypersplenism is
sometimes referred to as enlarged spleen (splenomegaly). An enlarged spleen is one of the symptoms of
hypersplenism. What differentiates hypersplenism is
its premature destruction of blood cells.

Causes and symptoms
Hypersplenism may be caused by a variety of
disorders. Sometimes, it is brought on by a problem
within the spleen itself and is referred to as primary
hypersplenism. Secondary hypersplenism results from
another disease such as chronic malaria, rheumatoid
arthritis, tuberculosis, or polycythemia vera, a blood
disorder. Spleen disorders in general are almost always
secondary in nature. Hypersplenism may also be
caused by tumors.
Symptoms of hypersplenism include easy bruising, easy contracting of bacterial diseases, fever, weakness, heart palpitations, and ulcerations of the mouth,
legs and feet. Individuals may also bleed unexpectedly
and heavily from the nose or other mucous membranes, and from the gastrointestinal or urinary tracts.
Most patients will develop an enlarged spleen, anemia,
leukopenia, or abnormally low white blood cell
counts, or thrombocytopenia, a deficiency of circulating
platelets in the blood. Other symptoms may be present
that reflect the underlying disease that has caused
hypersplenism.
An enlarged spleen can be caused by a variety of
diseases, including hemolytic anemia, liver cirrhosis,
leukemia, malignant lymphoma and other infections
and inflammatory diseases. Splenomegaly occurs in
about 10% of systemic lupus erythematosus patients.
Sometimes, it is caused by recent viral infection, such
as mononucleosis. An enlarged spleen may cause pain
in the upper left side of the abdomen and a premature
feeling of fullness at meals.

Diagnosis
Diagnosis of hypersplenism begins with review of
symptoms and patient history, and careful feeling
(palpation) of the spleen. Sometimes, a physician can
feel an enlarged spleen. X-ray studies, such as ultrasound and computed tomography scan (CT scan),
may help diagnose an enlarged spleen and possible
underlying causes, such as tumors. Blood tests indicate
decreases in white blood cells, red blood cells, or platelets. Another test measures red blood cells in the liver
and spleen after injection of a radioactive substance,
1900

KEY TERMS
Cirrhosis—Hardening of an organ, usually the
liver. Cirrhosis of the liver is a progressive disease
which leads to destruction of liver cells, interference with blood flow in the liver, and interference
with the function of the liver.
Palpitations—Throbbing or pulsation. Heart palpitations usually infer an irregular or rapid rhythm.
Polycythemia vera—A chronic disorder characterized by increased red blood cell mass and other
malfunctions of the blood system. It most commonly occurs in males of Jewish ancestry between
the ages of 40 and 60.
Systemic—Relating to a system, or especially the
entire system.
Systemic lupus erythematosus—A connective tissue disease that results in fever, weakness, fatigue,
joint pain and arthritis.
Ulcerations—Breaks in skin or mucous membranes that are often accompanied by loss of tissue
on the surface.

and indicates areas where the spleen is holding on to
large numbers of red cells or is destroying them.
Enlarged spleens are diagnosed using a combination of patient history, physical examination, including
palpation of the spleen, if possible, and diagnostic
tests. A history of fever and systemic symptoms may
be present because of infection, malaria, or an inflammatory disorder. A complete blood count is taken to
check counts of young red blood cells. Liver function
tests, CT scans, and ultrasound exams can also help to
detect an enlarged spleen.

Treatment
In secondary hypersplenism, the underlying disease must be treated to prevent further sequestration
or destruction of blood cells, and possible spleen
enlargement. Those therapies will be tried prior to
removal of the spleen (splenectomy), which is avoided
if possible. In severe cases, the spleen must be
removed. Splenectomy will correct the effects of low
blood cell concentrations in the blood.

Prognosis
Prognosis depends on the underlying cause and
progression of the disease. Left untreated, spleen
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Some of the underlying causes of hypersplenism
or enlarged spleen can be prevented, such as certain
forms of anemia and cirrhosis of the liver due to
alcohol. In other cases, the hypersplenism may not
be preventable, as it is a complication to an underlying
disorder.
Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
American Society of Hematology. 1200 19th Street NW,
Suite 300, Washington, DC 20036-2422. (202) 8571118. <http://www.hematology.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Teresa Norris, RN

Hypertension
Definition
Hypertension is high blood pressure. Blood pressure is the force of blood pushing against the walls of
arteries as it flows through them. Arteries are the
blood vessels that carry oxygenated blood from the
heart to the body’s tissues.

Description
As blood flows through arteries it pushes against
the inside of the artery walls. The more pressure the
blood exerts on the artery walls, the higher the blood
pressure will be. The size of small arteries also affects
the blood pressure. When the muscular walls of
arteries are relaxed, or dilated, the pressure of the
blood flowing through them is lower than when the
artery walls narrow, or constrict.
Blood pressure is highest when the heart beats to
push blood out into the arteries. When the heart
relaxes to fill with blood again, the pressure is at its
lowest point. Blood pressure when the heart beats is
GALE ENCYCLOPEDIA OF MEDICINE

called systolic pressure. Blood pressure when the heart
is at rest is called diastolic pressure. When blood pressure is measured, the systolic pressure is stated first
and the diastolic pressure second. Blood pressure is
measured in millimeters of mercury (mm Hg). For
example, if a person’s systolic pressure is 120 and
diastolic pressure is 80, it is written as 120/80 mm
Hg. The American Heart Association has long considred blood pressure less than 140 over 90 normal for
adults. However, the National Heart, Lung, and
Blood Institute in Bethesda, Maryland released new
clinical guidelines for blood pressure in 2003, lowering
the standard normal readings. A normal reading was
lowered to less than 120 over less than 80.
Hypertension is a major health problem, especially because it has no symptoms. Many people have
hypertension without knowing it. In the United States,
about 50 million people age six and older have high
blood pressure. Hypertension is more common in men
than women and in people over the age of 65 than in
younger persons. More than half of all Americans
over the age of 65 have hypertension. It also is more
common in African-Americans than in white
Americans.
Hypertension is serious because people with the
condition have a higher risk for heart disease and
other medical problems than people with normal
blood pressure. Serious complications can be avoided
by getting regular blood pressure checks and treating
hypertension as soon as it is diagnosed.
If left untreated, hypertension can lead to the
following medical conditions:


arteriosclerosis, also called atherosclerosis



heart attack



stroke



enlarged heart



kidney damage.

Arteriosclerosis is hardening of the arteries. The
walls of arteries have a layer of muscle and elastic
tissue that makes them flexible and able to dilate and
constrict as blood flows through them. High blood
pressure can make the artery walls thicken and
harden. When artery walls thicken, the inside of the
blood vessel narrows. Cholesterol and fats are more
likely to build up on the walls of damaged arteries,
making them even narrower. Blood clots also can get
trapped in narrowed arteries, blocking the flow of
blood.
Arteries narrowed by arteriosclerosis may not
deliver enough blood to organs and other tissues.
1901

Hypertension

enlargement can lead to serious complications.
Hypersplenism can also lead to complications due to
decreased blood cell counts.

Hypertension

Reduced or blocked blood flow to the heart can cause
a heart attack. If an artery to the brain is blocked, a
stroke can result.
Hypertension makes the heart work harder to
pump blood through the body. The extra workload
can make the heart muscle thicken and stretch. When
the heart becomes too enlarged it cannot pump
enough blood. If the hypertension is not treated, the
heart may fail.
The kidneys remove the body’s wastes from the
blood. If hypertension thickens the arteries to the
kidneys, less waste can be filtered from the blood. As
the condition worsens, the kidneys fail and wastes
build up in the blood. Dialysis or a kidney transplant
are needed when the kidneys fail. About 25% of people who receive kidney dialysis have kidney failure
caused by hypertension.

Causes and symptoms
Many different actions or situations can normally
raise blood pressure. Physical activity can temporarily
raise blood pressure. Stressful situations can make
blood pressure go up. When the stress goes away,
blood pressure usually returns to normal. These temporary increases in blood pressure are not considered
hypertension. A diagnosis of hypertension is made
only when a person has multiple high blood pressure
readings over a period of time.
The cause of hypertension is not known in 90 to 95
percent of the people who have it. Hypertension without a known cause is called primary or essential
hypertension.
When a person has hypertension caused by
another medical condition, it is called secondary
hypertension. Secondary hypertension can be caused
by a number of different illnesses. Many people
with kidney disorders have secondary hypertension.
The kidneys regulate the balance of salt and water in
the body. If the kidneys cannot rid the body of excess
salt and water, blood pressure goes up. Kidney infections, a narrowing of the arteries that carry blood
to the kidneys, called renal artery stenosis, and other
kidney disorders can disturb the salt and water
balance.
Cushing’s syndrome and tumors of the pituitary
and adrenal glands often increase levels of the adrenal
gland hormones cortisol, adrenalin, and aldosterone,
which can cause hypertension. Other conditions that
can cause hypertension are blood vessel diseases, thyroid gland disorders, some prescribed drugs, alcoholism, and pregnancy.
1902

Even though the cause of most hypertension is not
known, some people have risk factors that give them a
greater chance of getting hypertension. Many of these
risk factors can be changed to lower the chance of
developing hypertension or as part of a treatment
program to lower blood pressure.
Risk factors for hypertension include:


age over 60



male sex



race



heredity



salt sensitivity



obesity



inactive lifestyle



heavy alcohol consumption



use of oral contraceptives

Some risk factors for getting hypertension can be
changed, while others cannot. Age, male sex, and race
are risk factors that a person can’t do anything about.
Some people inherit a tendency to get hypertension.
People with family members who have hypertension
are more likely to develop it than those whose relatives
are not hypertensive. People with these risk factors can
avoid or eliminate the other risk factors to lower their
chance of developing hypertension. A 2003 report
found that the rise in incidence of high blood pressure
among children is most likely due to an increase in the
number of overweight and obese children and
adolescents.

Diagnosis
Because hypertension doesn’t cause symptoms, it
is important to have blood pressure checked regularly.
Blood pressure is measured with an instrument called
a sphygmomanometer. A cloth-covered rubber cuff is
wrapped around the upper arm and inflated. When the
cuff is inflated, an artery in the arm is squeezed to
momentarily stop the flow of blood. Then, the air is
let out of the cuff while a stethoscope placed over the
artery is used to detect the sound of the blood spurting
back through the artery. This first sound is the systolic
pressure, the pressure when the heart beats. The last
sound heard as the rest of the air is released is the
diastolic pressure, the pressure between heart beats.
Both sounds are recorded on the mercury gauge on the
sphygmomanometer.
Normal blood pressure is defined by a range of
values. Blood pressure lower than 120/80 mm Hg is
considered normal. A number of factors such as pain,
GALE ENCYCLOPEDIA OF MEDICINE

Hypertension

stress or anxiety can cause a temporary increase in
blood pressure. For this reason, hypertension is not
diagnosed on one high blood pressure reading. If a
blood pressure reading is 120/80 or higher for the first
time, the physician will have the person return for
another blood pressure check. Diagnosis of hypertension usually is made based on two or more readings
after the first visit.
Systolic hypertension of the elderly is common
and is diagnosed when the diastolic pressure is normal
or low, but the systolic is elevated, e.g.170/70 mm Hg.
This condition usually co-exists with hardening of the
arteries (atherosclerosis).
Blood pressure measurements are classified in
stages, according to severity:


normal blood pressure: less than less than 120/80 mm
Hg



pre-hypertension: 120–129/80–89 mm Hg



Stage 1 hypertension: 140–159/90–99 mm Hg



Stage 2 hypertension: at or greater than 160–179/
100–109 mm Hg

A typical physical examination to evaluate hypertension includes:


medical and family history



physical examination



ophthalmoscopy: Examination of the blood vessels
in the eye



chest x ray



electrocardiograph (ECG)



blood and urine tests.

The medical and family history help the physician
determine if the patient has any conditions or disorders that might contribute to or cause the hypertension. A family history of hypertension might suggest a
genetic predisposition for hypertension.
The physical exam may include several blood
pressure readings at different times and in different
positions. The physician uses a stethoscope to listen to
sounds made by the heart and blood flowing through
the arteries. The pulse, reflexes, and height and weight
are checked and recorded. Internal organs are
palpated, or felt, to determine if they are enlarged.
Because hypertension can cause damage to the
blood vessels in the eyes, the eyes may be checked
with a instrument called an ophthalmoscope. The
physician will look for thickening, narrowing, or
hemorrhages in the blood vessels.
GALE ENCYCLOPEDIA OF MEDICINE

The effects of hypertension on the heart and kidney.
Hypertension has caused renal atrophy and scarring, and
left ventricular hypertrophy in the sectioned heart (at right).
(Photograph by Dr. E. Walker, Photo Researchers, Inc.
Reproduced by permission.)

A chest x ray can detect an enlarged heart, other
vascular (heart) abnormalities, or lung disease.
An electrocardiogram (ECG) measures the electrical activity of the heart. It can detect if the heart
muscle is enlarged and if there is damage to the heart
muscle from blocked arteries.
Urine and blood tests may be done to evaluate
health and to detect the presence of disorders that
might cause hypertension.

Treatment
There is no cure for primary hypertension, but
blood pressure can almost always be lowered with
the correct treatment. The goal of treatment is to
lower blood pressure to levels that will prevent heart
disease and other complications of hypertension. In
secondary hypertension, the disease that is responsible
for the hypertension is treated in addition to the hypertension itself. Successful treatment of the underlying
disorder may cure the secondary hypertension.
Guidelines advise that clinicians work with
patients to agree on blood pressure goals and develop
a treatment plan for the individual patient. Actual
combinations of medications and lifestyle changes
will vary from one person to the next. Treatment to
lower blood pressure may include changes in diet,
getting regular exercise, and taking antihypertensive
medications. Patients falling into the pre-hypertension
range who don’t have damage to the heart or kidneys
often are advised to make needed lifestyle changes
only. A 2003 report of a clinical trial showed that
adults with elevated blood pressures lowered them
1903

Hypertension

as mush as 38% by making lifestyle changes and participating in the DASH diet, which encourages eating
more fruit and vegetables.
Lifestyle changes that may reduce blood pressure
by about 5 to 10 mm Hg include:


reducing salt intake



reducing fat intake



losing weight



getting regular exercise



quitting smoking



reducing alcohol consumption



managing stress

Patients whose blood pressure falls into the Stage
1 hypertension range may be advised to take antihypertensive medication. Numerous drugs have been
developed to treat hypertension. The choice of medication will depend on the stage of hypertension, side
effects, other medical conditions the patient may have,
and other medicines the patient is taking.
If treatment with a single medicine fails to lower
blood pressure enough, a different medicine may be
tried or another medicine may be added to the first.
Patients with more severe hypertension may initially
be given a combination of medicines to control their
hypertension. Combining antihypertensive medicines
with different types of action often controls blood
pressure with smaller doses of each drug than would
be needed for just one.
Antihypertensive medicines fall into several
classes of drugs:


diuretics



beta-blockers



calcium channel blockers



angiotensin converting enzyme inhibitors (ACE
inhibitors)



alpha-blockers



alpha-beta blockers



vasodilators



peripheral acting adrenergic antagonists



centrally acting agonists

Diuretics help the kidneys eliminate excess salt
and water from the body’s tissues and the blood.
This helps reduce the swelling caused by fluid buildup
in the tissues. The reduction of fluid dilates the walls of
arteries and lowers blood pressure. New guidelines
released in 2003 suggest diuretics as the first drug of
1904

choice for most patients with high blood pressure and
as part of any multi-drug combination.
Beta-blockers lower blood pressure by acting on
the nervous system to slow the heart rate and reduce
the force of the heart’s contraction. They are used with
caution in patients with heart failure, asthma, diabetes,
or circulation problems in the hands and feet.
Calcium channel blockers block the entry of calcium into muscle cells in artery walls. Muscle cells need
calcium to constrict, so reducing their calcium keeps
them more relaxed and lowers blood pressure.
ACE inhibitors block the production of substances that constrict blood vessels. They also help
reduce the build-up of water and salt in the tissues.
They often are given to patients with heart failure,
kidney disease, or diabetes. ACE inhibitors may be
used together with diuretics.
Alpha-blockers act on the nervous system to
dilate arteries and reduce the force of the heart’s
contractions.
Alpha-beta blockers combine the actions of alpha
and beta blockers.
Vasodilators act directly on arteries to relax their
walls so blood can move more easily through them.
They lower blood pressure rapidly and are injected in
hypertensive emergencies when patients have dangerously high blood pressure.
Peripheral acting adrenergic antagonists act on
the nervous system to relax arteries and reduce the
force of the heart’s contractions. They usually are
prescribed together with a diuretic. Peripheral acting
adrenergic antagonists can cause slowed mental function and lethargy.
Centrally acting agonists also act on the nervous
system to relax arteries and slow the heart rate.
They are usually used with other antihypertensive
medicines.

Prognosis
There is no cure for hypertension. However, it can
be well controlled with the proper treatment. Therapy
with a combination of lifestyle changes and antihypertensive medicines usually can keep blood pressure at
levels that will not cause damage to the heart or other
organs. The key to avoiding serious complications of
hypertension is to detect and treat it before damage
occurs. Because antihypertensive medicines control
blood pressure, but do not cure it, patients must continue taking the medications to maintain reduced
blood pressure levels and avoid complications.
GALE ENCYCLOPEDIA OF MEDICINE

Arteries—Blood vessels that carry blood to organs
and other tissues of the body.
Arteriosclerosis—Hardening and thickening of
artery walls.
Cushing’s syndrome—A disorder in which too much
of the adrenal hormone, cortisol, is produced; it may
be caused by a pituitary or adrenal gland tumor.
Diastolic blood pressure—Blood pressure when
the heart is resting between beats.
Hypertension—High blood pressure.
Renal artery stenosis—Disorder in which the
arteries that supply blood to the kidneys constrict.
Sphygmomanometer—An instrument used to measure blood pressure.
Systolic blood pressure—Blood pressure when the
heart contracts (beats).
Vasodilator—Any drug that relaxes blood vessel
walls.
Ventricle—One of the two lower chambers of the
heart.

McNamara, Damian. ‘‘Trial Shows Efficacy of Lifestyle
Changes for BP: More Intensive Than Typical Office
Visit.’’ Family Practice News July 1, 2003: 1-2.
‘‘New BP Guidelines Establish Diagnosis of Pre-hypertension: Level Seeks to Identify At-risk Individuals Early.’’
Case Management Advisor July 2003: S1.
‘‘New Hypertension Guidelines: JNC-7.’’ Clinical
Cardiology Alert July 2003: 54-63.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Toni Rizzo
Teresa G. Odle

Hyperthermia see Fever

Hyperthyroidism
Prevention

Definition

Prevention of hypertension centers on avoiding or
eliminating known risk factors. Even persons at risk
because of age, race, or sex or those who have an
inherited risk can lower their chance of developing
hypertension.

Hyperthyroidism is the overproduction of thyroid
hormones by an overactive thyroid.

The risk of developing hypertension can be
reduced by making the same changes recommended
for treating hypertension:

Located in the front of the neck, the thyroid gland
produces the hormones thyroxine (T4) and triiodothyronine (T3) that regulate the body’s metabolic
rate by helping to form protein ribonucleic acid
(RNA) and increasing oxygen absorption in every
cell. In turn, the production of these hormones are
controlled by thyroid-stimulating hormone (TSH)
that is produced by the pituitary gland. When production of the thyroid hormones increases despite the level
of TSH being produced, hyperthyroidism occurs. The
excessive amount of thyroid hormones in the blood
increases the body’s metabolism, creating both mental
and physical symptoms.



reducing salt intake



reducing fat intake



losing weight



getting regular exercise



quitting smoking



reducing alcohol consumption



managing stress

Resources
PERIODICALS

McNamara, Damian. ‘‘Obesity Behind Rise in Incidence of
Primary Hypertension.’’ Family Practice News April 1,
2003: 45-51.
GALE ENCYCLOPEDIA OF MEDICINE

Description

The term hyperthyroidism covers any disease
which results in overabundance of thyroid hormone.
Other names for hyperthyroidism, or specific diseases
within the category, include Graves’ disease, diffuse
toxic goiter, Basedow’s disease, Parry’s disease, and
thyrotoxicosis. The disease is 10 times more common
1905

Hyperthyroidism

KEY TERMS

Hyperthyroidism

in women than in men, and the annual incidence of
hyperthyroidism in the United States is about one per
1,000 women. Although it occurs at all ages,
hyperthyroidism is most likely to occur after the age
of 15. There is a form of hyperthyroidism called
Neonatal Grave’s disease, which occurs in infants
born of mothers with Graves’ disease. Occult
hyperthyroidism may occur in patients over 65 and is
characterized by a distinct lack of typical symptoms.
Diffuse toxic goiter occurs in as many as 80% of
patients with hyperthyroidism.

Causes and symptoms
Hyperthyroidism is often associated with the
body’s production of autoantibodies in the blood
which cause the thyroid to grow and secrete excess
thyroid hormone. This condition, as well as other
forms of hyperthyroidism, may be inherited.
Regardless of the cause, hyperthyroidism produces
the same symptoms, including weight loss with
increased appetite, shortness of breath and fatigue,
intolerance to heat, heart palpitations, increased frequency of bowel movements, weak muscles, tremors,
anxiety, and difficulty sleeping. Women may also
notice decreased menstrual flow and irregular menstrual cycles.
Patients with Graves’ disease often have a goiter
(visible enlargement of the thyroid gland), although
as many as 10% do not. These patients may also
have bulging eyes. Thyroid storm, a serious form of
hyperthyroidism, may show up as sudden and acute
symptoms, some of which mimic typical hyperthyroidism, as well as the addition of fever, substantial weakness, extreme restlessness, confusion, emotional
swings or psychosis, and perhaps even coma.

Diagnosis
Physicians will look for physical signs and symptoms indicated by patient history. On inspection, the
physician may note symptoms such as a goiter or eye
bulging. Other symptoms or family history may be
clues to a diagnosis of hyperthyroidism. An elevated
body temperature (basal body temperature) above
98.6  F (37  C) may be an indication of a heightened
metabolic rate (basal metabolic rate) and hyperthyroidism. A simple blood test can be performed to
determine the amount of thyroid hormone in the
patient’s blood. The diagnosis is usually straightforward with this combination of clinical history, physical examination, and routine blood hormone tests.
Radioimmunoassay, or a test to show concentrations
of thyroid hormones with the use of a radioisotope
1906

A symptom of hyperthyroidism is the enlargement of the
thyroid gland. (Photograph by Lester V. Bergman, Corbis
Images. Reproduced by permission.)

mixed with fluid samples, helps confirm the diagnosis.
A thyroid scan is a nuclear medicine procedure involving injection of a radioisotope dye which will tag the
thyroid and help produce a clear image of inflammation or involvement of the entire thyroid. Other tests
can determine thyroid function and thyroid-stimulating
hormone levels. Ultrasonography, computed tomography scans (CT scan), and magnetic resonance
imaging (MRI) may provide visual confirmation of
a diagnosis or help to determine the extent of
involvement.

Treatment
Treatment will depend on the specific disease and
individual circumstances such as age, severity of disease, and other conditions affecting a patient’s health.

Antithyroid drugs
Antithyroid drugs are often administered to help
the patient’s body cease overproduction of thyroid
hormones. This medication may work for young
GALE ENCYCLOPEDIA OF MEDICINE

Radioactive iodine
Radioactive iodine is often prescribed to damage
cells that make thyroid hormone. The cells need
iodine to make the hormone, so they will absorb
any iodine found in the body. The patient may take
an iodine capsule daily for several weeks, resulting in
the eventual shrinkage of the thyroid in size, reduced
hormone production and a return to normal blood
levels. Some patients may receive a single larger oral
dose of radioactive iodine to treat the disease more
quickly. This should only be done for patients who
are not of reproductive age or are not planning to
have children, since a large amount can concentrate
in the reproductive organs (gonads).
Surgery
Some patients may undergo surgery to treat
hyperthyroidism. Most commonly, patients treated
with thyroidectomy, in the form of partial or total
removal of the thyroid, suffer from large goiter and
have suffered relapses, even after repeated attempts to
address the disease through drug therapy. Some
patients may be candidates for surgery because they
were not good candidates for iodine therapy, or
refused iodine administration. Patients receiving thyroidectomy or iodine therapy must be carefully monitored for years to watch for signs of hypothyroidism,
or insufficient production of thyroid hormones, which
can occur as a complication of thyroid production
suppression.

KEY TERMS
Goiter—Chronic enlargement of the thyroid gland.
Gonads—Organs that produce sex cells—the ovaries and testes.
Palpitations—Rapid and forceful heartbeat.
Radioisotope—A chemical tagged with radioactive
compounds that is injected during a nuclear medicine procedure to highlight organ or tissue.
Thyroidectomy—Removal of the thyroid gland.

threatening and can lead to heart, liver, or kidney
failure.

Prevention
There are no known prevention methods for
hyperthyroidism, since its causes are either inherited
or not completely understood. The best prevention
tactic is knowledge of family history and close attention to symptoms and signs of the disease. Careful
attention to prescribed therapy can prevent complications of the disease.
Resources
ORGANIZATIONS

Thyroid Foundation of America. 350 Ruth Sleeper Hall RSL 350, Parkman St., Boston, MA. 02114. (800) 8328321. <http://www.clark.net/pub/tfa>.
OTHER

‘‘Endocrine Disorder and Endocrine Surgery.’’
Endocrine Web Page. <http://
www.endocrineweb.com>.

Teresa Odle

Alternative treatment
Consumption of foods such as broccoli, brussel
sprouts, cabbage, cauliflower, kale, rutabagas, spinach, turnips, peaches, and pears can help naturally
suppress thyroid hormone production. Caffeinated
drinks and dairy products should be avoided. Under
the supervision of a trained physician, high dosages
of certain vitamin/mineral combinations can help
alleviate hyperthyroidism.

Prognosis
Hyperthyroidism is generally treatable and carries
a good prognosis. Most patients lead normal lives with
proper treatment. Thyroid storm, however, can be lifeGALE ENCYCLOPEDIA OF MEDICINE

Hypertrophic cardiomyopathy
Definition
Cardiomyopathy is an ongoing disease process
that damages the muscle wall of the lower chambers
of the heart. Hypertrophic cardiomyopathy is a
form of cardiomyopathy in which the walls of the
heart’s chambers thicken abnormally. Other names
for hypertrophic cardiomyopathy are idiopathic
1907

Hypertrophic cardiomyopathy

adults, pregnant women, and others. Women who are
pregnant should be treated with the lowest dose
required to maintain thyroid function in order to
minimize the risk of hypothyroidism in the infant.

Hypertrophic cardiomyopathy

hypertrophic subaortic stenosis and asymmetrical
septal hypertrophy.

Description
Hypertrophic cardiomyopathy usually appears in
young people, often in athletes. For this reason it is
sometimes called athletic heart muscle disease.
However, people of any age can develop hypertrophic
cardiomyopathy. Often there are no symptoms of
hypertrophic cardiomyopathy. Sudden death can
occur, caused by a heart arrhythmia. The American
Heart Association reports that 36% of young athletes
who die suddenly have probable or definite hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy is the result of
abnormal growth of the heart muscle cells. The wall
between the heart’s chambers (the septum) may
become so thickened that it blocks the flow of blood
through the lower left chamber (left ventricle). The
thickened wall may push on the heart valve between
the two left heart chambers (mitral valve), making it
leaky. The thickened muscle walls also prevent the
heart from stretching as much as it should to fill with
blood.

Causes and symptoms
The cause of hypertrophic cardiomyopathy is not
known. In about one-half of cases, the disease is inherited. An abnormal gene has been identified in these
patients. In cases that are not hereditary, a gene that
was normal at birth may later become abnormal.
Often people with hypertrophic cardiomyopathy
have no symptoms. Unfortunately, the first sign of the
condition may be sudden death caused by an abnormal heart rhythm. When symptoms do appear, they
include shortness of breath on exertion, dizziness, fainting, fatigue, and chest pain.

Diagnosis
The diagnosis is based on the patient’s symptoms
(if any), a complete physical examination, and tests
that detect abnormalities of the heart chambers.
Usually, there is an abnormal heart murmur that worsens with the Valsalva maneuver. The electrocardiogram (ECG), which provides a record of electrical
changes in the heart muscle during the heartbeat,
also is typically abnormal.
Sometimes, a routine chest x ray may show that
the heart is enlarged. Echocardiography, a procedure
that produces images of the heart’s structure, is
1908

This illustration shows hypertrophic muscle in the heart. The
abnormally thick wall of muscle prevents the chambers from
stretching to fill up with blood, making the heart less efficient.
The extra tissue may also push on the heart valve (center),
causing it to leak. (Illustration by Bryson Biomedical Illustrations,
Custom Medical Stock Photo. Reproduced by permission.)

usually done. These images can show if the heart wall
is thickened and if there are any abnormalities of the
heart valves.

Treatment
Treatment of hypertrophic cardiomyopathy
usually consists of taking medicines and restricting
strenuous exercise. Drugs called beta blockers and
calcium channel blockers are usually prescribed. Beta
blockers reduce the force of the heart’s contractions.
Calcium channel blockers can help improve the flexibility of the heart muscle walls, allowing them to
stretch more. Antiarrhythmic drugs may also be
given to prevent abnormal heart rhythms.
Patients with hypertrophic cardiomyopathy are
also told to avoid strenuous exercise to reduce the
risk of passing out or sudden death.
In some cases, if the medications do not help
relieve symptoms, surgery may help. In an operation
called myotomy-myectomy a piece of the septum is
removed to improve blood flow through the heart
chamber.
GALE ENCYCLOPEDIA OF MEDICINE

Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Arrhythmias—Abnormal heartbeat.

Toni Rizzo

Calcium channel blocker—A drug that relaxes
blood vessels and lowers blood pressure.
Mitral valve—The heart valve that controls blood
flow between the heart’s left upper chamber
(atrium) and left lower chamber (ventricle).
Septum—The muscular wall dividing the left and
right heart chambers.
Ventricles—The two lower chambers of the heart.

Hypervitaminosis see Vitamin toxicity

Hyphema
Definition

Some patients have pacemakers and/or defibrillators implanted to help control the heart rate and
rhythm. Pacemakers and defibrillators provide electrical impulses to the heart, which can return the heart
beat to a normal rhythm.
If these treatment methods fail and a patient
develops heart failure, a heart transplant may be
necessary.

Prognosis
Some people with hypertrophic cardiomyopathy
may not have obstructed blood flow and may never
experience symptoms. Others may only experience
mild symptoms. With treatment, symptoms may
improve. In some patients, the disease may progress
to heart failure.

A hyphema is an accumulation of blood in the
front (anterior) chamber of the eye. It is usually caused
by blunt eye trauma.

Description
The anterior chamber (AC) is located behind the
front of the eye. The AC is filled with a fluid called
aqueous humor. This fluid helps form a cushion for
the eye and provides an important route for nutrient
and waste transport. Contusive forces from high
velocity projectiles (approximately 34% of emergency
room cases) such as a rock, crab apples, ice balls,
badminton birds, and bungee cords can tear local
blood vessels in the eye. Blunt impact from a basketball or racketball accounts for about 62% of cases.
Tearing a small blood vessel can cause seepage of
blood into a visible layer portion of the AC, causing
the affected person to have red eye.

Prevention
While hypertrophic cardiomyopathy cannot be
prevented, precautionary measures may prevent sudden deaths. Anyone planning to take part in a program of strenuous competitive exercise should have a
checkup by a physician first. A physical examination
before athletic participation can usually, but not
always, detect conditions like hypertrophic cardiomyopathy. Anyone who experiences symptoms of
shortness of breath, tiredness, or fainting with exercise
should see a physician.
Resources

Causes and symptoms
Hyphema is caused by blunt, projectile, or explosion (about 4% of cases) injuries. These injuries cause
a local blood vessel in the eye to tear, filling the front
portion of the AC with blood. The initial complaint is
a dramatic decrease in vision that eventually gets better as blood seeps towards the back of the eye. Patients
will have extreme pain, an increase in intraocular
pressure (the pressure inside the eye), and nausea.
Patients usually will show a red eye and a recent history of trauma. Patients are vulnerable to more bleeding three to five days post injury.

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
All persons with hyphema must be examined by
an ophthalmologist (a physician who specializes in the
medical and surgical care of the eye). Usually
the clinician will use an ophthalmoscope to visualize
1909

Hyphema

KEY TERMS

Hypnotherapy

KEY TERMS
Microhyphema—Small bleed in the anterior chamber of the eye.
Ophthalmologist—A physician with specialized
training in the medical and surgical treatment of
eye diseases.
Optic Nerve—A cranial nerve that carries visual
impulses to the brain for processing

the internal structures and damage. In some cases
there may be small microscopic bleeds that may form
clots (microhyphema) and require specialized instrumentation (a slit lamp) for visualization.

Treatment
Bloodthinners, such as aspirin and nonsteroidal
anti-inflammatory drugs, should be avoided. In most
cases the affected person can be medically managed on
an outpatient basis. The eye should be shielded, but
not patched. The patient should be placed at bed rest
with the head elevated 45  . This position allows blood
to leave the AC allowing for better vision. Several
studies suggest administering medications (aminocaproic acid) that stabilize clot formation, reducing the
possibility of increased bleeding.

Prognosis
The outcome depends on the severity of the
trauma. Most cases progress well with conservative
treatment. Some cases may develop an increase in the
pressure within the eye (glaucoma). If this develops the
hyphema must be surgically removed by an ophthalmologist. In patients who have a preexisting blood
disorder, surgical evacuation should be considered to
prevent damage to the optic nerve (the nerve that
transmits impulses for processing in the brain).

Prevention
The American Academy of Ophthalmology
recommends special eyewear made of polycarbonate
lenses when at risk of eye injury. This type of lens has
sufficient impact resistance.
Resources
BOOKS

Behrman, Richard E., et al, editors. Nelson Textbook of
Pediatrics. 16th ed. W. B. Saunders Company, 2000.
1910

Yanoff, Myron, et al, editors. Ophthalmology. Mosby
International Ltd., 1999.

Laith Farid Gulli, M.D.

Hypnosis see Hypnotherapy

Hypnotherapy
Definition
Hypnotherapy is the treatment of a variety of
health conditions by hypnotism or by inducing prolonged sleep.
Pioneers in this field, such as James Braid and
James Esdaile discovered that hypnosis could be used
to successfully anesthetize patients for surgeries.
James Braid accidentally discovered that one of his
patients began to enter a hypnotic state while staring
at a fixed light as he waited for his eye examination to
begin. Since mesmerism had fallen out of favor, Braid
coined the term hypnotism, which is derived from the
Greek word for sleep. Braid also used the techniques
of monotony, rhythm, and imitation to assist in inducing a hypnotic state. As of 2000, these techniques are
still in use.
Around 1900, there were very few preoperative
anesthetic drugs available. Patients were naturally
apprehensive when facing surgery. One out of four
hundred patients would die, not from the surgical
procedure, but from the anesthesia. Dr. Henry
Munro was one of the first physicians to use hypnotherapy to alleviate patient fears about having surgery. He would get his patients into a hypnotic state
and discuss their fears with them, telling them they
would feel a lot better following surgery. Ether was the
most common anesthetic at that time, and Dr. Munro
found that he was able to perform surgery using only
about 10% of the usual amount of ether.

Purpose
Hypnotherapy is used in a number of fields
including psychotherapy, surgery, dentistry, research,
and medicine. Hypnotherapy is commonly used as an
alternative treatment for a wide range of health conditions, including weight control, pain management,
and smoking cessation. It is also used to control pain
in a variety of conditions such as headache, facial
neuralgia, arthritis, burns, musculoskeletal disorders,
childbirth, and many more. Hypnotherapy is being
GALE ENCYCLOPEDIA OF MEDICINE

Hypnotherapy is used for nonmedical patients as
well as those who wish to overcome bad habits.
Hypnotherapy has been shown to help those who
suffer from performance anxiety, such as in sports,
and speaking in public. In academic applications, it
has also been shown to help with learning, participating in the classroom, concentrating, studying, focusing attention span, improving memory, and helping
remove mental blocks about particular subjects.
In more general areas, hypnotherapy has been
found to be beneficial for problems such as motivation, procrastination, decision making, personal
achievement and development, job performance, buried
or repressed memories, relaxation, and stress
management.

Description
Origins
Hypnotherapy is thought to date back to the healing practices of ancient Greece and Egypt. Many religions such as Judaism, Christianity, Islam, and others
have attributed trance-like behavior to spiritual or
divine possession.
Austrian physician, Franz Mesmer (1734–1815),
is credited with being the first person to scientifically
investigate the idea of hypnotherapy, in 1779, to treat
a variety of health conditions. Mesmer studied medicine at the University of Vienna and received his medical degree in 1766. Mesmer is believed to have been
the first doctor to understand the relationship of psychological trauma to illness. He induced a trance-like
state, which became known as mesmerism, in his
patients to successfully treat nervous disorders.
These techniques became the foundation for modernday hypnotherapy.
Mesmer’s original interest was in the effect of
celestial bodies on human lives. He later became interested in the effects of magnetism, and found that
magnets could have tremendous healing effects on
the human body. Mesmer believed that the human
body contained a magnetic fluid that promoted health
and well being. It was thought that any blockage to the
normal flow of this magnetic fluid would result in
GALE ENCYCLOPEDIA OF MEDICINE

illness, and that the use of the mesmerism technique
could restore the normal flow.
Mesmer performed his technique by passing his
hands up and down the patient’s body. The technique
was supposed to transmit magnetic fluid from his
hands to the bodies of his patients. During this time
period, there was no clear delineation between health
conditions that were physical or psychological in
nature. Although Mesmer did not realize it at that
time, his treatments were most effective for those conditions that were primarily psychosomatic.
Mesmer’s technique appeared to be quite successful in the treatment of his patients, but he was the
subject of scorn and ridicule from the medical profession. Because of all the controversy surrounding
mesmerism, and because Mesmer’s personality was
quite eccentric, a commission was convened to investigate his techniques and procedures. A very distinguished panel of investigators included Benjamin
Franklin, the French chemist Antoine-Laurent
Lavoisier, and physician Jacques Guillotin. The commission acknowledged that patients did seem to obtain
noticeable relief from their conditions, but the whole
idea was dismissed as being medical quackery.
It took more than two hundred years for hypnotherapy to become incorporated into medical treatment. In 1955, the British Medical Association
approved the use of hypnotherapy as a valid medical
treatment, with the American Medical Association
(AMA) giving its approval in 1958.
Hypnotherapy involves achieving a psychological
state of awareness that is different from the ordinary
state of consciousness. While in a hypnotic state, a
variety of phenomena can occur. These phenomena
include alterations in memory, heightened susceptibility to suggestion, paralysis, sweating, and blushing.
All of these changes can be produced or removed in
the hypnotic state. Many studies have shown that
roughly 90% of the population is capable of being
hypnotized.
This state of awareness can be achieved by relaxing the body, focusing on breathing, and shifting
attention away from the external environment. In
this state, the patient has a heightened receptivity to
suggestion. The usual procedure for inducing a hypnotic trance in another person is by direct command
repeated in a soothing, monotonous tone of voice.

Preparations
Ideally, the following conditions should be present to successfully achieve a state of hypnosis:
1911

Hypnotherapy

used in place of anesthesia, particularly in patients
who prove to be allergic to anesthetic drugs, for surgeries such as hysterectomies, cesarean sections, certain cardiovascular procedures, thyroidectomy, and
others. Dentistry is using hypnotherapy with success
on patients who are allergic to all types of novocaine
drugs. Hypnotherapy is also useful in helping patients
overcome phobias.

Hypnotherapy



willingness to be hypnotized



rapport between the patient or client and the
hypnotherapist



a comfortable environment that is conducive to
relaxation

Precautions
Hypnotherapy can have negative outcomes. When
used as entertainment, people have been hypnotized to
say or do things that would normally embarrass them.
There have been instances where people already dangerously close to psychological breakdown have been
pushed into an emotional crisis during what was supposed to be a harmless demonstration of hypnosis.
A statement from the World Hypnosis Organization
(WHO) warns against performing hypnosis on patients
suffering from psychosis, organic psychiatric conditions, or antisocial personality disorders. Because there
are no standard licensing requirements, in the wrong
hands, there is a risk that the hypnotist will have difficulty in controlling or ending a hypnotic state that has
been induced in the patient.
There is a commonly held belief that a person
cannot be coerced into doing things that they would
not normally do while under hypnosis. The
hynotherapist should take care however, not to give
suggestions during hypnosis that are contrary to the
patient’s moral code.
Many religions do not condone the practice of
hypnotherapy. Leaders of the Jehovah’s Witnesses
and Christian Science religions oppose the use of hypnotherapy and advise their members to avoid it completely, whether for entertainment or therapy. The
Church of Jesus Christ of Latter-Day Saints approves
it for medical purposes, but cautions members against
allowing themselves to be hypnotized for entertainment or demonstration purposes.
In 1985, The AMA convened a commission that
warned against using hypnotherapy to aid in recollection of events. The commission cited studies that
showed the possibility of hypnotic recall resulting on
confabulation or an artificial sense of certainty about
the course of events. As a result, many states limit or
prohibit testimony of hypnotized witnesses or victims.

Side effects
Experiments have been conducted to determine
any side effects of hypnotherapy. Some subjects have
reported side effects such as headache, stiff neck, drowsiness, cognitive distortion or confusion, dizziness, and
1912

anxiety. However, most of these effects cleared up
within several hours of the hypnotherapy session.

Research and general acceptance
Research on the effectiveness of hypnotherapy on
a variety of medical conditions is extensive. In one
study, the use of hypnotherapy did not seem to alter
the core symptoms in the treatment of attention-deficit
hyperactivity disorder (ADHD); however, it did seem
to be useful in managing the associated symptoms
including sleep disturbances and tics.
Hypnotherapy is being studied in children who
have common, chronic problems and to aid in relieving pain. Children are particularly good candidates for
hypnotherapy because their lack of worldly experience
enables them to move easily between the rational
world and their imagination. Studies with children
have shown responses to hypnotherapy ranging from
diminished pain and anxiety during a number of medical procedures, a 50% range in reduction of symptoms or a complete resolution of a medical condition,
and a reduction in use of anti-nausea medication and
vomiting during chemotherapy for childhood cancers.
The use of hypnotherapy with cancer patients is
another area being investigated. A meta-analysis of
116 studies showed very positive results of using hypnotherapy with cancer patients. Ninety-two percent
showed a positive effect on depression; 93% showed
a positive effect on physical well-being; 81% showed a
positive effect on vomiting; and 92% showed a positive effect on pain.
Resources
PERIODICALS

Baumgaertel, Anna. ‘‘Attention-Deficit/Hyperactivity
Disorder:Alternative and Controversial Treatments for
Attention-Deficit/Hyperactivity Disorder.’’Pediatric
Clinics of North America October 1999.
Margolis, Clorinda G. ‘‘Hypnotic Trance: The Old and the
New.’’Primary Care Clinics in Office Practice.
Newell, Sallie, and Rob W. Sanson-Fisher. ‘‘Australian on
Bologists’ self-reported knowledge and attitudes about
non-traditional therapies used by cancer patients.’’
Medical Journal of Australia February 7, 2000.
ORGANIZATIONS

American Board of Hypnotherapy. 16842 Von Karman
Avenue, Suite 476, Irvine, CA 92714. <http://
www.hypnosis.com>.
American Psychotherapy & Medical Hypnosis Association.
210 S. Sierra, Reno, NV 89501. <http://members.
xoom.com/Hypnosis>.
American Society of Clinical Hypnosis. 200 E. Devon
Avenue, Des Plaines, IL 60018.
GALE ENCYCLOPEDIA OF MEDICINE

Kim A. Sharp, M.Ln.

Hypocalcemia
Definition
Hypocalcemia, a low bood calcium level, occurs
when the concentration of free calcium ions in the
blood falls below 4.0 mg/dL (dL=one tenth of a
liter). The normal concentration of free calcium ions
in the blood serum is 4.0–6.0 mg/dL.

Description
Calcium is an important mineral for maintaining
human helath. It is not only a component of bones and
teeth, but is also essential for normal blood clotting
and necessary for normal muscle and nerve functions.
The calcium ion (Ca2+) has two positive charges. In
bone, calcium ions occur as a complex with phosphate
to form crystals of calcium phosphate. In the bloodstream, calcium ions also occur in complexes, and here
calcium is found combined with proteins and various
nutrients. However, in the bloodstream, calcium also
occurs in a free form. Normally, about 47% of the
calcium in the blood plasma is free, while 53% occurs
in a complexed form. Although all of the calcium in
the bloodstream serves a useful purpose, it is only the
concentration of free calcium ions which has a direct
influence on the functioning of our nerves and muscles. For this reason, the measurement of the concentration of free calcium is more important, in the
diagnosis of disease, than measuring the level of total
GALE ENCYCLOPEDIA OF MEDICINE

calcium or of complexed calcium. The level of total
calcium in the blood serum is normally 8.5–10.5 mg/
dL, while the level of free calcium is normally 4–5 mg/dl.

Causes and symptoms
Hypocalcemia can be caused by hypoparathyroidism, by failure to produce 1,25-dihydroxyvitamin D,
by low levels of plasma magnesium, or by failure to
get adequate amounts of calcium or vitamin D in the
diet. Hypoparathyroidism involves the failure of the
parathyroid gland to make parathyroid hormone.
Parathyroid hormone controls and maintains plasma
calcium levels. The hormone exerts its effect on the
kidneys, where it triggers the synthesis of 1,25-dihydroxyvitamin D. Thus, hypocalcemia can be independently caused by damage to the parathyroid gland or
to the kidneys. 1,25-Dihydroxyvitamin D stimulates
the uptake of calcium from the diet and the mobilization of calcium from the bone. Bone mobilization
means the natural process by which the body dissolves
part of the bone in the skeleton in order to maintain or
raise the levels of plasma calcium ions.
Low plasma magnesium levels (hypomagnesia)
can result in hypocalcemia. Hypomagnesemia can
occur with alcoholism or with diseases characterized
by an inability to properly absorb fat. Magnesium is
required for parathyroid hormone to play its part in
maintaining plasma calcium levels. For this reason,
any disease that results in lowered plasma magnesium
levels may also cause hypocalcemia.
Hypocalcimia may also result from the consumption of toxic levels of phosphate. Phosphate is a constituent of certain enema formulas. An enema is a
solution that is used to cleanse the intestines via a
hose inserted into the rectum. Cases of hypocalcemia
have been documented where people swallowed
enema formulas, or where an enema has been administered to an infant.
Symptoms of severe hypocalcemia include numbness or tingling around the mouth or in the feet and
hands, as well as in muscle spasms in the face, feet, and
hands. Hypocalcemia can also result in depression,
memory loss, or hallucinations. Severe hypocalcemia
occurs when serum free calcium is under 3 mg/dL.
Chronic and moderate hypocalcemia can result in
cataracts (damage to the eyes). In this case, the term
‘‘chronic’’ means lasting one year or longer.

Diagnosis
Hypocalcemia is diagnosed by acquiring a sample
of blood serum and measuring the concentraton of
1913

Hypocalcemia

International Council for Medical and Clinical Therapists.
7361 McWhorter Place, Suite 300, Annandale, VA
22003-5469. <http://www.ultradepth.com/
ICMCT.htm>.
International Medical and Dental Hypnotherapy
Association. 4110 Edgeland, Suite 800, Royal Oak, MI
48073-2285. <http://www.infinityinst.com>.
National Board for Hypnotherapy and Hypnotic
Anaesthesiology. 7841 West Ludlow Drive, Suite A,
Peoria, AZ 85381. <http://www.nbha-medicine.com/
index.html>.
National Guild of Hypnotists. PO Box 308, Merrimack,
NH. <http://www.ngh.net>.
Society for Clinical and Experimental Hypnosis. 6728 Old
McLean Village Drive, McLean, VA 22101.
World Hypnosis Organization, Inc. 2521 W. Montrose
Avenue, Chicago, IL 60618. <http://www.
worldhypnosis.org/about.html>.

Hypochondriasis

KEY TERMS

by reducing alcohol consumption and increasing the
intake of healthful food.

Plasma—Plasma is blood with the cells removed.

Resources

Serum—Serum is blood plasma with the blood
clotting proteins removed.

BOOKS

Brody, Tom. Nutritional Biochemistry. San Diego:Academic
Press, 1998.

Tom Brody, PhD
free calcium using a calcium-sensitive electrode.
Hypocalcemia has several causes, and hence a full
diagnosis requires assessment of health of the parathyroid gland, kidneys, and of plasma magnesium
concentration.

Treatment
The method chosen for treatment depends on the
exact cause and on the severity of the hypocalcemia.
Severe hypocalcemia requires injection of calcium ions,
usually in the form of calcium gluconate. Oral calcium
supplements are prescribed for long term treatment
(non-emergency) of hypocalcemia. The oral supplements may take the form of calcium carbonate, calcium
chloride, calcium lactate, or calcium gluconate. Where
hypocalcemia results from kidney failure, treatment
includes injections of 1,25-dihydroxyvitamin D. Oral
vitamin D supplements can increase gastrointestinal
absorption of calcium. Where hypocalcemia results
from hypoparathyroidism, treatment may include oral
calcium, 1,25-dihydroxyvitamin D, or other drugs.
Where low serum magnesium levels occur, concurrently
with hypocalcemia, the magnesium deficiency must be
corrected to effectively treat the hypocalcemia.

Hypochondriac see Hypochondriasis

Hypochondriasis
Definition
Hypochondriasis is a mental disorder characterized by excessive fear of or preoccupation with a serious illness, despite medical testing and reassurance to
the contrary. It was formerly called hypochondriacal
neurosis.

Description
Although hypochondriasis is often considered a
disorder that primarily affects adults, it is now increasingly recognized in children and adolescents. In addition, hypochondriasis may develop in elderly people
without previous histories of health-related fears. The
disorder accounts for about 5% of psychiatric patients
and is equally common in men and women.

Causes and symptoms
Prognosis
The prognosis for correcting hypocalcemia is
excellent. However, the eye damage that may result
from chronic hypocalcemia cannot be reversed.

Prevention
The first, and most obvious, way to help prevent
hypocalcemia is to ensure that adequate amounts of
calcium and vitamin D are consumed each day, either
in the diet or as supplements. The hypocalcemia that
may occur with damage to the parathyroid gland or to
the kidneys cannot be prevented. Hypocalcemia
resulting from overuse of enemas can be prevented by
reducing enema usage. Hypocalcemia resulting from
magnesium deficiency tends to occur in chronic alcoholics, and this type of hypocalcemia can be prevented
1914

The causes of hypochondriasis are not precisely
known. Children may have physical symptoms that
resemble or mimic those of other family members. In
adults, hypochondriasis may sometimes reflect a selfcentered character structure or a wish to be taken care
of by others; it may also have been copied from a
parent’s behavior. In elderly people, hypochondriasis
may be associated with depression or grief. It may also
involve biologically based hypersensitivity to internal
stimuli.
Most hypochondriacs are worried about being
physically sick, although some express fear of insanity.
The symptoms reported can range from general
descriptions of a specific illness to unusual complaints.
In many instances the symptoms reflect intensified
awareness of ordinary body functions, such as heartbeat, breathing, or stomach noises. It is important to
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
The diagnosis is often complicated by the patient’s
detailed understanding of symptoms and medical
terminology from previous contacts with doctors. If
a new doctor suspects hypochondriasis, he or she will
usually order a complete medical workup in order to
rule out physical disease.

KEY TERMS
Somatoform disorder—A category of psychiatric
disorder characterized by conversion of emotional
distress into physical symptoms or by symptoms of
physical illness that have no discernible organic
cause. Hypochondriasis is classified as a somatoform disorder.
Supportive therapy—Any form of treatment
intended to relieve symptoms or help the patient
live with them rather than attempt changes in character structure.

Psychological evaluation is also necessary to rule
out other disorders that involve feelings of anxiety or
complaints of physical illness. These disorders include
depression, panic disorder, and schizophrenia with
somatic (physical) delusions. The following features
are characteristic of hypochondriasis:

From 33–50% of patients with hypochondriasis
can expect significant improvement from the current
methods of treatment.

The patient is not psychotic (out of touch with reality
or hallucinating).

Resources









The patient gets upset or blames the doctor when
told there is ‘‘nothing wrong,’’ or that there is a
psychological basis for the problem.
There is a correlation between episodes of hypochondriacal behavior and stressful periods in the patient’s
life.
The behavior has lasted at least six months.

Evaluation of children and adolescents with
hypochondriasis should include the possibility of
abuse by family members.

Treatment

Prognosis

BOOKS

Eisendrath, Stuart J. ‘‘Psychiatric Disorders.’’ In Current
Medical Diagnosis and Treatment, 1998, edited by
Stephen McPhee, et al., 37th ed. Stamford: Appleton &
Lange, 1997.

Rebecca J. Frey, PhD

Hypoesthesias see Numbness and tingling

Hypoglycemia

The goal of therapy is to help the patient (and
family) live with the symptoms and to modify thinking
and behavior that reinforces hypochondriacal symptoms. This treatment orientation is called supportive,
as distinct from insight-oriented, because hypochondriacs usually resist psychological interpretations of
their symptoms. Supportive treatment may include
medications to relieve anxiety. Some clinicians look
carefully for ‘‘masked’’ depression and treat with
antidepressants.

The condition called hypoglycemia is literally
translated as low blood sugar. Hypoglycemia occurs
when blood sugar (or blood glucose) concentrations
fall below a level necessary to properly support the
body’s need for energy and stability throughout its
cells.

Follow-up care includes regular physical checkups, because about 30% of patients with hypochondriasis will eventually develop a serious physical
illness. The physician also tries to prevent unnecessary
medical testing and ‘‘doctor shopping’’ on the
patient’s part.

Carbohydrates are the main dietary source of the
glucose that is manufactured in the liver and absorbed
into the bloodstream to fuel the body’s cells and
organs. Glucose concentration is controlled by hormones, primarily insulin and glucagon. Glucose concentration also is controlled by epinephrine

GALE ENCYCLOPEDIA OF MEDICINE

Definition

Description

1915

Hypoglycemia

understand that a hypochondriac’s symptoms are not
‘‘in the head’’ in the sense of being delusional. The
symptoms are real, but the patient misinterprets bodily functions and attributes them to a serious or even
lethal cause.

Hypoglycemia

(adrenalin) and norepinephrine, as well as growth
hormone. If these regulators are not working properly,
levels of blood sugar can become either excessive (as in
hyperglycemia) or inadequate (as in hypoglycemia). If
a person has a blood sugar level of 50 mg/dl or less, he
or she is considered hypoglycemic, although glucose
levels vary widely from one person to another.
Hypoglycemia can occur in several ways.
Drug-induced hypoglycemia
Drug-induced hypoglycemia, a complication of
diabetes, is the most commonly seen and most dangerous form of hypoglycemia.
Hypoglycemia occurs most often in diabetics who
must inject insulin periodically to lower their blood
sugar. While other diabetics also are vulnerable to low
blood sugar episodes, they have a lower risk of a
serious outcome than insulin-dependant diabetics.
Unless recognized and treated immediately, severe
hypoglycemia in the insulin-dependent diabetic can
lead to generalized convulsions followed by amnesia
and unconsciousness. Death, though rare, is a possible
outcome.
In insulin-dependent diabetics, hypoglycemia
known as an insulin reaction or insulin shock can be
caused by several factors. These include overmedicating with manufactured insulin, missing or delaying a
meal, eating too little food for the amount of insulin
taken, exercising too strenuously, drinking too much
alcohol, or any combination of these factors.
Ideopathic or reactive hypoglycemia
Ideopathic or reactive hypoglycemia (also called
postprandial hypoglycemia) occurs when some people
eat. A number of reasons for this reaction have been
proposed, but no single cause has been identified.
In some cases, this form of hypoglycemia appears
to be associated with malfunctions or diseases of the
liver, pituitary, adrenals, liver, or pancreas. These conditions are unrelated to diabetes. Children intolerant
of a natural sugar (fructose) or who have inherited
defects that affect digestion also may experience hypoglycemic attacks. Some children with a negative reaction to aspirin also experience reactive hypoglycemia.
It sometimes occurs among people with an intolerance
to the sugar found in milk (galactose), and it also often
begins before diabetes strikes later on.
Fasting hypoglycemia
Fasting hypoglycemia sometimes occurs after long
periods without food, but it also happens occasionally
1916

following strenuous exercise, such as running in a
marathon.
Other factors sometimes associated with hypoglycemia include:


pregnancy



a weakened immune system



a poor diet high in simple carbohydrates



prolonged use of drugs, including antibiotics



chronic physical or mental stress



heartbeat irregularities (arrhythmias)



allergies



breast cancer



high blood pressure treated with beta-blocker medications (after strenuous exercise)



upper gastrointestinal tract surgery.

Causes and symptoms
When carbohydrates are eaten, they are converted
to glucose that goes into the bloodstream and is distributed throughout the body. Simultaneously, a combination of chemicals that regulate how our body’s
cells absorb that sugar is released from the liver, pancreas, and adrenal glands. These chemical regulators
include insulin, glucagon, epinephrine (adrenalin),
and norepinephrine. The mixture of these regulators
released following digestion of carbohydrates is never
the same, since the amount of carbohydrates that are
eaten is never the same.
Interactions among the regulators are complicated. Any abnormalities in the effectiveness of any
one of the regulators can reduce or increase the body’s
absorption of glucose. Gastrointestinal enzymes such
as amylase and lactase that break down carbohydrates
may not be functioning properly. These abnormalities
may produce hyperglycemia or hypoglycemia, and can
be detected when the level of glucose in the blood is
measured.
Cell sensitivity to these regulators can be changed
in many ways. Over time, a person’s stress level, exercise patterns, advancing age, and dietary habits influence cellular sensitivity. For example, a diet
consistently overly rich in carbohydrates increases
insulin requirements over time. Eventually, cells can
become less receptive to the effects of the regulating
chemicals, which can lead to glucose intolerance.
Diet is both a major factor in producing hypoglycemia as well as the primary method for controlling it.
Diets typical of western cultures contain excess
GALE ENCYCLOPEDIA OF MEDICINE

Early symptoms of severe hypoglycemia, particularly in the drug-induced type of hypoglycemia, resemble an extreme shock reaction. Symptoms include:

Because all of its possible symptoms are not likely
to be seen in any one person at a specific time, diagnosing hypoglycemia can be difficult. One or more of
its many symptoms may be due to another illness.
Symptoms may persist in a variety of forms for long
periods of time. Symptoms also can change over time
within the same person. Some of the factors that can
influence symptoms include physical or mental activities, physical or mental state, the amount of time
passed since the last meal, the amount and quality of
sleep, and exercise patterns.



cold and pale skin

Diagnosis



numbness around the mouth

Drug-induced hypoglycemia



apprehension



heart palpitations



emotional outbursts



hand tremors



mental cloudiness



dilated pupils



sweating



fainting

Mild attacks, however, are more common in reactive hypoglycemia and are characterized by extreme
tiredness. Patients first lose their alertness, then their
muscle strength and coordination. Thinking grows
fuzzy, and finally the patient becomes so tired that he
or she becomes ‘‘zombie-like,’’ awake but not functioning. Sometimes the patient will actually fall asleep.
Unplanned naps are typical of the chronic hypoglycemic patient, particularly following meals.
Additional symptoms of reactive hypoglycemia
include headaches, double vision, staggering or inability to walk, a craving for salt and/or sweets, abdominal
distress, premenstrual tension, chronic colitis, allergies,
ringing in the ears, unusual patterns in the frequency of
urination, skin eruptions and inflammations, pain in
the neck and shoulder muscles, memory problems,
and sudden and excessive sweating.
Unfortunately, a number of these symptoms
mimic those of other conditions. For example, the
depression, insomnia, irritability, lack of concentration, crying spells, phobias, forgetfulness, confusion,
unsocial behavior, and suicidal tendencies commonly
seen in nervous system and psychiatric disorders also
may be hypoglycemic symptoms. It is very important
that anyone with symptoms that may suggest reactive
hypoglycemia see a doctor.
GALE ENCYCLOPEDIA OF MEDICINE

Once diabetes is diagnosed, the patient then monitors his or her blood sugar level with a portable
machine called a glucometer. The diabetic places a
small blood sample on a test strip that the machine
can read. If the test reveals that the blood sugar level is
too low, the diabetic can make a correction by eating
or drinking an additional carbohydrate.
Reactive hypoglycemia
Reactive hypoglycemia only can be diagnosed
by a doctor. Symptoms usually improve after the
patient has gone on an appropriate diet. Reactive
hypoglycemia was diagnosed more frequently 10–20
years ago than today. Studies have shown that most
people suffering from its symptoms test normal for
blood sugar, leading many doctors to suggest that
actual cases of reactive hypoglycemia are quite rare.
Some doctors think that people with hypoglycemic
symptoms may be particularly sensitive to the body’s
normal postmeal release of the hormone epinephrine,
or are actually suffering from some other physical
or mental problem. Other doctors believe reactive
hypoglycemia actually is the early onset of diabetes
that occurs after a number of years. There continues
to be disagreement about the cause of reactive
hypoglycemia.
A common test to diagnose hypoglycemia is the
extended oral glucose tolerance test. Following an
overnight fast, a concentrated solution of glucose is
drunk and blood samples are taken hourly for five to
six hours. Though this test remains helpful in early
identification of diabetes, its use in diagnosing chronic
reactive hypoglycemia has lost favor because it can
trigger hypoglycemic symptoms in people with otherwise normal glucose readings. Some doctors now
recommend that blood sugar be tested at the actual
time a person experiences hypoglycemic symptoms.
1917

Hypoglycemia

carbohydrates, especially in the form of simple carbohydrates such as sweeteners, which are more easily
converted to sugar. In poorer parts of the world, the
typical diet contains even higher levels of carbohydrates. Fewer dairy products and meats are eaten,
and grains, vegetables, and fruits are consumed. This
dietary trend is balanced, however, since people in
these cultures eat smaller meals and usually use carbohydrates more efficiently through physical labor.

Hypoglycemia

Treatment
Treatment of the immediate symptoms of hypoglycemia can include eating sugar. For example, a
patient can eat a piece of candy, drink milk, or drink
fruit juice. Glucose tablets can be used by patients,
especially those who are diabetic. Effective treatment
of hypoglycemia over time requires the patient to
follow a modified diet. Patients usually are encouraged to eat small, but frequent, meals throughout the
day, avoiding excess simple sugars (including alcohol),
fats, and fruit drinks. Those patients with severe hypoglycemia may require fast-acting glucagon injections
that can stabilize their blood sugar within approximately 15 minutes.

Alternative treatment
A holistic approach to reactive hypoglycemia is
based on the belief that a number of factors may create
the condition. Among them are heredity, the effects of
other illnesses, emotional stress, too much or too little
exercise, bad lighting, poor diet, and environmental
pollution. Therefore, a number of alternative methods
have been proposed as useful in treating the condition.
Homeopathy, acupuncture, and applied kinesiology,
for example, have been used, as have herbal remedies.
One of the herbal remedies commonly suggested for
hypoglycemia is a decoction (an extract made by boiling) of gentian (Gentiana lutea). It should be drunk
warm 15–30 minutes before a meal. Gentian is
believed to help stimulate the endocrine (hormoneproducing) glands.
In addition to the dietary modifications recommended above, people with hypoglycemia may benefit
from supplementing their diet with chromium, which
is believed to help improve blood sugar levels.
Chromium is found in whole grain breads and cereals,
cheese, molasses, lean meats, and brewer’s yeast.
Hypoglycemics should avoid alcohol, caffeine, and
cigarette smoke, since these substances can cause significant swings in blood sugar levels.

severe hypoglycemia but not know it. Those who don’t
pay attention to severe hypoglycemia events or who
have had previous severe hypoglycemia are the most
likely to have future severe hypoglycemia. An audible
alert can let the patient know immediately that he or
she needs to take care of his or her blood sugar level.
Continuous monitoring has proved particularly helpful in pediatric patients with Type 1 diabetes.
Maintaining proper diet also is a factor.
Programmable insulin pumps implanted under the
skin have proven useful in reducing the incidence of
hypoglycemic episodes for insulin-dependent diabetics. As of late 1997, clinical studies continue to
seek additional ways to control diabetes and druginduced hypoglycemia. Tests of a substance called
pramlintide indicate that it may help improve glycemic
control in diabetics.
Reactive hypoglycemia
The onset of reactive hypoglycemia can be
avoided or at least delayed by following the same
kind of diet used to control it. While not as restrictive
as the diet diabetics must follow to keep tight control
over their disease, it is quite similar.
There are a variety of diet recommendations for
the reactive hypoglycemic. Patients should:


avoiding overeating



never skipping breakfast



including protein in all meals and snacks, preferably
from sources low in fat, such as the white meat of
chicken or turkey, most fish, soy products, or skim
milk



restricting intake of fats (particularly saturated fats,
such as animal fats), and avoiding refined sugars and
processed foods



being aware of the differences between some vegetables, such as potatoes and carrots. These vegetables
have a higher sugar content than others (like squash
and broccoli). Patients should be aware of these
differences and note any reactions they have to them.



being aware of differences found in grain products.
White flour is a carbohydrate that is rapidly
absorbed into the bloodstream, while oats take
much longer to break down in the body.



keeping a ‘‘food diary.’’ Until the diet is stabilized, a
patient should note what and how much he/she eats
and drinks at every meal. If symptoms appear following a meal or snack, patients should note them
and look for patterns.

Prevention
Drug-induced hypoglycemia
Preventing hypoglycemic insulin reactions in diabetics requires taking glucose readings through frequent blood sampling. Insulin then can be regulated
based on those readings. Continuous glucose monitoring sensors have been developed to help diabetics
remain more aware of possible hypoglycemic episodes. These monitors even can check for episodes
while the patient sleeps, when many will experience
1918

GALE ENCYCLOPEDIA OF MEDICINE

Adrenal glands—Two organs that sit atop the kidneys; these glands make and release hormones
such as epinephrine.
Epinephrine—Also called adrenalin, a secretion of
the adrenal glands (along with norepinephrine) that
helps the liver release glucose and limits the release
of insulin. Norepinephrine is both a hormone and a
neurotransmitter, a substance that transmits nerve
signals.
Fructose—A type of natural sugar found in many
fruits, vegetables, and in honey.
Glucagon—A hormone produced in the pancreas
that raises the level of glucose in the blood. An
injectable form of glucagon, which can be bought
in a drug store, is sometimes used to treat insulin
shock.
Postprandial—After eating or after a meal.





eat fresh fruits, but restrict the amount they eat at
one time. Patients should remember to eat a source of
protein whenever they eat high sources of carbohydrate like fruit. Apples make particularly good
snacks because, of all fruits, the carbohydrate in
apples is digested most slowly.
following a diet that is high in fiber. Fruit is a good
source of fiber, as are oatmeal and oat bran. Fiber slows
the buildup of sugar in the blood during digestion.

These people may lose notice of the automatic warning symptoms of hypoglycemia that normally occur as
their bodies become so used to frequent periods of
hypoglycemia. It is not a permanent event, but can
be treated by careful avoidance of hypoglycemia for
about two weeks.
Resources
BOOKS

Ruggiero, Roberta. The Do’s and Don’ts of Low Blood Sugar.
Hollywood, FL: Frederick Fell Publishers.
PERIODICALS

Brauker, James, et al. ‘‘Use of Continuous Glucose
Monitoring Alerts to Better Predict, Prevent and Treat
Postprandial Hyperglycemia.’’ Diabetes June 2003:
90-91.
Gertzman, Jerilyn, et al. ‘‘Severity of Hypoglycemia and
Hypoglycemia Unawareness Are Associated with the
Extent of Unsuspected Nocturnal Hypoglycemia.’’
Diabetes June 2003:146-151.
Kumar, Rajeev, and Miles Fisher. ‘‘Impaired Hypoglycemia
Awareness: Are we Aware?’’ Diabetes and Primary Care
Summer 2004: 33–38.
Ludvigsson, Johnny, and Ragnar Hanas. ‘‘Continuous
Subcutaneous Glucose Monitoring Improved
Metabolic Control in Pediatric Patients With Type 1
Diabetes: A Controlled Crossover Study.’’ Pediatrics
May 2003: 933-936.
ORGANIZATIONS

Hypoglycemia Association, Inc. 18008 New Hampshire
Ave., PO Box 165, Ashton, MD 20861-0165.
National Hypoglycemia Association, Inc. PO Box 120,
Ridgewood, NJ 07451. (201) 670-1189.

Martin W. Dodge, PhD
Teresa G. Odle

A doctor can recommend a proper diet, and there
are many cookbooks available for diabetics. Recipes
found in such books are equally effective in helping to
control hypoglycemia.

Prognosis
Like diabetes, there is no cure for reactive hypoglycemia, only ways to control it. While some chronic
cases will continue through life (rarely is there complete
remission of the condition), others will develop into
type II (age onset) diabetes. Hypoglycemia appears to
have a higher-than-average incidence in families where
there has been a history of hypoglycemia or diabetes
among their members, but whether hypoglycemia is a
controllable warning of oncoming diabetes has not yet
been determined by clinical research.
A condition known as hypoglycemia unawareness
can develop in those who do not control their blood
glucose, particularly in people with Type 1 diabetes.
GALE ENCYCLOPEDIA OF MEDICINE

Hypogonadism
Definition
Hypogonadism is the condition more prevalent in
males in which the production of sex hormones and
germ cells are inadequate.

Description
Gonads are the organs of sexual differentiation—
in the female, they are ovaries; in the male, the testes.
Along with producing eggs and sperm, they produce
sex hormones that generate all the differences between
men and women. If they produce too little sex
1919

Hypogonadism

KEY TERMS

Hypogonadism

hormone, then either the growth of the sexual organs
or their function is impaired.
The gonads are not independent in their function,
however. They are closely controlled by the pituitary
gland. The pituitary hormones are the same for males
and females, but the gonadal hormones are different.
Men produce mostly androgens, and women produce
mostly estrogens. These two hormones regulate the
development of the embryo, determining whether it is a
male or a female. They also direct the adolescent maturation of sex organs into their adult form. Further, they
sustain those organs and their function throughout the
reproductive years. The effects of estrogen reach beyond
that to sustain bone strength and protect the cardiovascular system from degenerative disease.
Hormones can be inadequate during or after each
stage of development—embryonic and adolescent.
During each stage, inadequate hormone stimulation
will prevent normal development. After each stage, a
decrease in hormone stimulation will result in failed
function and perhaps some shrinkage. The organs
affected principally by sex hormones are the male and
female genitals, both internal and external, and the
female breasts. Body hair, fat deposition, bone and muscle growth, and some brain functions are also influenced.

Causes and symptoms
Sex is determined at the moment of conception by
sex chromosomes. Females have two X chromosomes,
while males have one X and one Y chromosome. If the
male sperm with the Y chromosome fertilizes an egg,
the baby will be male. This is true throughout the
animal kingdom. Genetic defects sometimes result in
changes in the chromosomes. If sex chromosomes are
involved, there is a change in the development of sexual characteristics.
Female is the default sex of the embryo, so most of
the sex organ deficits at birth occur in boys. Some, but
not all, are due to inadequate androgen stimulation.
The penis may be small, the testicles undescended
(cryptorchidism) or various degrees of ‘‘feminization’’
of the genitals may be present.
After birth, sexual development does not occur
until puberty. Hypogonadism most often shows up as
an abnormality in boys during puberty. Again, not
every defect is due to inadequate hormones. Some
are due to too much of the wrong ones. Kallmann’s
syndrome is a birth defect in the brain that prevents
release of hormones and appears as failure of male
puberty. Some boys have adequate amounts of androgen in their system but fail to respond to them, a
condition known as androgen resistance.
1920

KEY TERMS
Biopsy—Surgical removal of pieces of tissue for
examination.
Embryo—Refers to life before birth, specifically the
first two months after conception.
Fetus—The unborn person or animal, still in the
womb.
Hypothalamus—Part of the brain just above the
pituitary that stimulates pituitary gland function.
Ionizing radiation—X rays. Diagnostic x rays are
too weak to do damage under normal circumstances, but x rays used to treat cancer must be
used with great care.
Undescended testicle—A testicle that is still in the
groin and has not made its way into the scrotum.

Female problems in puberty are not caused by too
little estrogen. Even female reproductive problems
are rarely related to a simple lack of hormones, but
rather to complex cycling rhythms gone wrong. All the
problems with too little hormone happen during
menopause, which is a normal hypogonadism.
A number of adverse events can damage the
gonads and result in decreased hormone levels. The
childhood disease mumps, if acquired after puberty,
can infect and destroy the testicles—a disease called
viral orchitis. Ionizing radiation and chemotherapy,
trauma, several drugs (spironolactone, a diuretic and
ketoconazole, an antifungal agent), alcohol, marijuana, heroin, methadone, and environmental toxins
can all damage testicles and decrease their hormone
production. Severe diseases in the liver or kidneys,
certain infections, sickle cell anemia, and some cancers
also affect gonads. To treat some male cancers, it is
necessary to remove the testicles, thereby preventing
the androgens from stimulating cancer growth. This
procedure, still called castration or orchiectomy,
removes androgen stimulation from the whole body.
For several reasons the pituitary can fail. It happens rarely after pregnancy. It used to be removed to
treat advanced breast or prostate cancer. Sometimes
the pituitary develops a tumor that destroys it. Failure
of the pituitary is called hypopituitarism and, of
course, leaves the gonads with no stimulation to produce hormones.
Besides the tissue changes generated by hormone
stimulation, the only other symptoms relate to sexual
desire and function. Libido is enhanced by testosterone,
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Presently, there are accurate blood tests for most
of the hormones in the body, including those from the
pituitary and even some from the hypothalamus.
Chromosomes can be analyzed, and gonads can, but
rarely are, biopsied.

Treatment
Replacement of missing body chemicals is much
easier than suppressing excesses. Estrogen replacement
is recommended for nearly all women after menopause
for its many beneficial effects. Estrogen can be taken by
mouth, injection, or skin patch. It is strongly recommended that the other female hormone, progesterone,
be taken as well, because it prevents overgrowth of
uterine lining and uterine cancer. Testosterone replacement is available for males who are deficient.

millimolarity [mM], however, both units are identical
and mean the same thing when applied to concentrations of potassium ions.)
Hypokalemia can result from two general causes:
either from an overall depletion in the body’s potassium or from excessive uptake of potassium by muscle
from surrounding fluids.

Description
A normal adult weighing about 154 lbs (70 kg) has
about 3.6 moles of potassium ions in his body. Most of
this potassium (about 98%) occurs inside various cells
and organs, where normal concentration are about
150 mM. Blood serum concentrations are much
lower—only about 0.4% of the body’s potassium is
found in blood serum. As noted above, hypokalemia
can be caused by the sudden uptake of potassium
ions from the bloodstream by muscle or other organs
or by an overall depletion of the body’s potassium.
Hypokalemia due to overall depletion tends to be a
chronic phenomenon, while hypokalemia due to a
shift in location tends to be a temporary disorder.

Causes and symptoms

Resources
BOOKS

Carr, Bruce R., and Karen D. Bradshaw. ‘‘Disorders of the
Ovary and Female Reproductive Tract.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony S.
Fauci, et al. New York: McGraw-Hill, 1998.

J. Ricker Polsdorfer, MD

Hypokalemia
Definition
Hypokalemia is a condition of below normal
levels of potassium in the blood serum. Potassium, a
necessary electrolyte, facilitates nerve impulse conduction and the contraction of skeletal and smooth
muscles, including the heart. It also facilitates cell
membrane function and proper enzyme activity.
Levels must be kept in a proper (homeostatic) balance
for the maintenance of health. The normal concentration of potassium in the serum is in the range of 3.5–
5.0 mM. Hypokalemia means serum or plasma levels
of potassium ions that fall below 3.5 mM. (Potassium
concentrations are often expressed in units of milliequivalents per liter [mEq/L], rather than in units of
GALE ENCYCLOPEDIA OF MEDICINE

Hypokalemia is most commonly caused by the use
of diuretics. Diuretics are drugs that increase the excretion of water and salts in the urine. Diuretics are used
to treat a number of medical conditions, including
hypertension (high blood pressure), congestive heart
failure, liver disease, and kidney disease. However,
diuretic treatment can have the side effect of producing hypokalemia. In fact, the most common cause of
hypokalemia in the elderly is the use of diuretics. The
use of furosemide and thiazide, two commonly used
diuretic drugs, can lead to hypokalemia. In contrast,
spironolactone and triamterene are diuretics that do
not provoke hypokalemia.
Other commons causes of hypokalemia are excessive diarrhea or vomiting. Diarrhea and vomiting can
be produced by infections of the gastrointestinal tract.
Due to a variety of organisms, including bacteria,
protozoa, and viruses, diarrhea is a major world
health problem. It is responsible for about a quarter
of the 10 million infant deaths that occur each year.
Although nearly all of these deaths occur in the poorer
parts of Asia and Africa, diarrheal diseases are a leading cause of infant death in the United States. Diarrhea
results in various abnormalities, such as dehydration
(loss in body water), hyponatremia (low sodium level
in the blood), and hypokalemia.
Because of the need for potassium to control muscle action, hypokalemia can cause the heart to stop
1921

Hypokalemia

and male sexual performance requires androgens. The
role of female hormones in female sexual activity is
less clear, although hormones strengthen tissues and
promote healthy secretions, facilitating sexual activity.

Hypokalemia

beating. Young infants are especially at risk for death
from this cause, especially where severe diarrhea continues for two weeks or longer. Diarrhea due to laxative
abuse is an occasional cause of hypokalemia in the
adolescent or adult. Enema abuse is a related cause of
hypokalemia. Laxative abuse is especially difficult to
diagnose and treat, because patients usually deny the
practice. Up to 20% of persons complaining of chronic
diarrhea practice laxative abuse. Laxative abuse is often
part of eating disorders, such as anorexia nervosa or
bulimia nervosa. Hypokalemia that occurs with these
eating disorders may be life-threatening.
Surprisingly, the potassium loss that accompanies
vomiting is only partly due to loss of potassium from
the vomit. Vomiting also has the effect of provoking
an increase in potassium loss in the urine. Vomiting
expels acid from the mouth, and this loss of acid
results in alkalization of the blood. (Alkalization of
the blood means that the pH of the blood increases
slightly.) An increased blood pH has a direct effect on
the kidneys. Alkaline blood provokes the kidneys to
release excessive amounts of potassium in the urine.
So, severe and continual vomiting can cause excessive
losses of potassium from the body and hypokalemia.

such as Liddle’s syndrome, Bartter’s syndrom, and
Franconi’s syndrome; and eating too much licorice.
Symptoms
Mild hypokalemia usually results in no symptoms,
while moderate hypokalemia results in confusion, disorientation, weakness, and discomfort of muscles. On
occasion, moderate hypokalemia causes cramps during
exercise. Another symptom of moderate hypokalemia
is a discomfort in the legs that is experienced while
sitting still. The patient may experience an annoying
feeling that can be relieved by shifting the positions of
the legs or by stomping the feet on the floor. Severe
hypokalemia results in extreme weakness of the body
and, on occasion, in paralysis. The paralysis that occurs
is ‘‘flaccid paralysis,’’ or limpness. Paralysis of the
muscles of the lungs results in death. Another dangerous result of severe hypokalemia is abnormal heart
beat (arrhythmia) that can lead to death from cardiac
arrest (cessation of heart beat). Moderate hypokalemia
may be defined as serum potassium between 2.5 and
3.0 mM, while severe hypokalemia is defined as serum
potassium under 2.5 mM.

A third general cause of hypokalemia is prolonged
fasting and starvation. In most people, after three
weeks of fasting, blood serum potassium levels will
decline to below 3.0 mM and result in severe hypokalemia. However, in some persons, serum potassium
may be naturally maintained at about 3.0 mM, even
after 100 days of fasting. During fasting, muscle is
naturally broken down, and the muscle protein is
converted to sugar (glucose) to supply to the brain
the glucose which is essential for its functioning.
Other organs are able to survive with a mixed supply
of fat and glucose. The potassium within the muscle
cell is released during the gradual process of muscle
breakdown that occurs with starvation, and this can
help counteract the trend to hypokalemia during starvation. Eating an unbalanced diet does not cause
hypokalemia because most foods, such as fruits (especially bananas, oranges, and melons), vegetables,
meat, milk, and cheese, are good sources of potassium.
Only foods such as butter, margarine, vegetable oil,
soda water, jelly beans, and hard candies are extremely
poor in potassium.

Hypokalemia can be measured by acquiring a
sample of blood, preparing blood serum, and using a
potassium sensitive electrode for measuring the concentration of potassium ions. Atomic absorption spectroscopy can also be used to measure the potassium
ions. Since hypokalemia results in abnormalities in
heart behavior, the electrocardiogram is usually used
in the diagnosis of hypokalemia. The diagnosis of the
cause of hypokalemia can be helped by measuring the
potassium content of the urine. Where urinary potassium is under 25 mmoles per day, it means that the
patient has experienced excessive losses of potassium
due to diarrhea. The urinary potassium test is useful in
cases where the patient is denying the practice of
laxative or enema abuse. In contrast, where hypokalemia is due to the use of diuretic drugs, the content of
potassium in the urine will be high—over 40 mmoles
per day.

Alcoholism occasionally results in hypokalemia.
About one half of alcoholics hospitalized for withdrawal symptoms experience hypokalemia. The hypokalemia of alcoholics occurs for a variety of reasons,
usually poor nutrition, vomiting, and diarrhea.
Hypokalemia can also be caused by hyperaldosteronism; Cushing’s syndrome; hereditary kidney defects

In emergency situations, when severe hypokalemia is suspected, the patient should be put on a cardiac
monitor, and respiratory status should be assessed.
If laboratory test results show potassium levels below
2.5 mM, intravenous potassium should be given. In
less urgent cases, potassium can be given orally in the
pill form. Potassium supplements take the form of pills

1922

Diagnosis

Treatment

GALE ENCYCLOPEDIA OF MEDICINE

Hypolipoproteinemia

Diuretics—A class of drugs that cause the kidneys
to excrete excess sodium, water, and potassium.
pH—The unit of acid content is pH. The blood
plasma normally has a pH of 7.35–7.45. Acidic
blood has a pH value slightly less than pH 7.35.
Alkaline blood has a pH value slightly greater than
pH 7.45.
Potassium—An electrolyte necessary to proper
functioning of the body.

containing potassium chloride (KCl), potassium
bicarbonate (KHCO3), and potassium acetate. Oral
potassium chloride is the safest and most effective
treatment for hypokalemia. Generally, the consumption of 40–80 mmoles of KCl per day is sufficient to
correct the hypokalemia that results from diuretic
therapy. For many people taking diuretics, potassium
supplements are not necessary as long as they eat a
balanced diet containing foods rich in potassium.

Prognosis
The prognosis for correcting hypokalemia is
excellent. However, in emergency situations, where
potassium is administered intravenously, the physician must be careful not to give too much potassium.
The administration of potassium at high levels, or at a
high rate, can lead to abnormally high levels of serum
potassium.

Definition
Hypolipoproteinemia (or hypolipidemia) is the
lack of fat in the blood.

Description
Although quite rare, hypolipoproteinemia is a
serious condition. Blood absorbs fat from food in the
intestine and transports it as a combined package with
proteins and other chemicals like cholesterol. Much of
the fat goes straight into the liver for processing. The
cholesterol, a waste product, ends up in the bile. The
proteins act as vessels, carrying the other chemicals
around. These packages of fat, cholesterol, and proteins are called lipoproteins.

Causes and symptoms
Low blood fats can be the result of several diseases, or they can be a primary genetic disease with
other associated abnormalities.


Malnutrition is a lack of food, including fats, in the
diet.



Malabsorption is the inability of the bowel to absorb
food, causing malnutrition.



Anemia (too few red blood cells) and hyperthyroidism (too much thyroid hormone) also reduce blood
fats.



Rare genetic conditions called hypobetalipoproteinemia and abetalipoproteinemia cause malabsorption plus nerve, eye, and skin problems in early
childhood.



Tangier disease, causes only the cholesterol to be
low. It also produces nerve and eye problems in
children.

Prevention
Hypokalemia is not a concern for healthy persons,
since potassium is present in a great variety of foods.
For patients taking diuretics, however, the American
Dietetic Association recommends use of a high potassium diet. The American Dietetic Association states
that if hypokalemia has already occurred, use of the
high potassium diet alone may not reverse hypokalemia. Useful components of a high potassium diet
include bananas, tomatoes, cantaloupes, figs, raisins,
kidney beans, potatoes, and milk.
Resources
BOOKS

Brody, Tom. Nutritional Biochemistry. San Diego:Academic
Press, 1998.

Tom Brody, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms are associated more closely with the
cause rather than the actual low blood fats.

Diagnosis
Blood studies of the various fat particles help
identify both the low and high fat diseases. These
tests are often done after an overnight fast to prevent
interference from fat just being absorbed from food.
Fats and proteins are grouped together and described
by density—high-density lipoproteins (HDL), lowdensity lipoproteins (LDL), and very low-density lipoproteins (VLDL). There are also much bigger particles
1923

Hypolipoproteinemia

KEY TERMS

Hyponatremia

KEY TERMS
Cholesterol—A steroid alcohol found in animal
cells and fluids.
Lipoprotein—Class of proteins that contain protein
and lipid. The fundamental component of living
cells.

called chylomicrons. Each contain different proportions of cholesterol, fats, and protein.

Treatment
Supplemental vitamin E helps children with the
betalipoprotein deficiencies. There is no known treatment for Tangier disease. Treatment of the causes of
the other forms of low blood fats reverses the
condition.
Resources
BOOKS

Ginsberg, Henry N., and Ira J. Goldberg. ‘‘Disorders Of
Lipoprotein Metabolism.’’ In Harrison’s Principles of
Internal Medicine, edited by Anthony S. Fauci, et al.
New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Hypomagnesemia see Magnesium
imbalance

(NaHCO3) are commonly occurring salts. These salts
can be dissolved in water or in juices of various foods.
Dissolving involves the complete separation of ions,
such as sodium and chloride in common table salt
(NaCl).
About 40% of the body’s sodium is contained in
bone. Approximately 2–5% occurs within organs and
cells and the remaining 55% is in blood plasma and
other extracellular fluids. The amount of sodium in
blood plasma is typically 140 mM, a much higher
amount than is found in intracellular sodium (about
5 mM). This asymmetric distribution of sodium ions is
essential for human life. It makes possible proper
nerve conduction, the passage of various nutrients
into cells, and the maintenance of blood pressure.
The body continually regulates its handling of
sodium. When dietary sodium is too high or low, the
intestines and kidneys respond to adjust concentrations to normal. During the course of a day, the intestines absorb dietary sodium while the kidneys excrete a
nearly equal amount of sodium into the urine. If a low
sodium diet is consumed, the intestines increase their
efficiency of sodium absorption, and the kidneys
reduce its release into urine.
The concentration of sodium in the blood plasma
depends on two things: the total amount of sodium
and water in arteries, veins, and capillaries (the circulatory system). The body uses separate mechanisms to
regulate sodium and water, but they work together to
correct blood pressure when it is too high or too low.
Too low a concentration of sodium, or hyponatremia,
can be corrected either by increasing sodium or by
decreasing body water. The existence of separate
mechanisms that regulate sodium concentration
account for the fact that there are numerous diseases
that can cause hyponatremia, including diseases of the
kidney, pituitary gland, and hypothalamus.

Hyponatremia
Definition
The normal concentration of sodium in the blood
plasma is 136–145 mM. Hyponatremia occurs when
sodium falls below 130 mM. Plasma sodium levels
of 125 mM or less are dangerous and can result in
seizures and coma.

Description
Sodium is an atom, or ion, that carries a single
positive charge. The sodium ion may be abbreviated as
Na+ or as simply Na. Sodium can occur as a salt in a
crystalline solid. Sodium chloride (NaCl), sodium
phosphate (Na2HPO4) and sodium bicarbonate
1924

Causes and symptoms
Hyponatremia can be caused by abnormal consumption or excretion of dietary sodium or water and
by diseases that impair the body’s ability to regulate
them. Maintenance of a low salt diet for many months
or excessive sweat loss during a race on a hot day can
present a challenge to the body to conserve adequate
sodium levels. While these conditions alone are not
likely to cause hyponatremia, it can occur under special circumstances. For example, hyponatremia often
occurs in patients taking diuretic drugs who maintain
a low sodium diet. This is especially of concern in
elderly patients, who have a reduced ability to regulate
the concentrations of various nutrients in the
GALE ENCYCLOPEDIA OF MEDICINE

Severe and prolonged diarrhea can also cause
hyponatremia. Severe diarrhea, causing the daily output of 8–10 liters of fluid from the large intestines,
results in the loss of large amounts of water, sodium,
and various nutrients. Some diarrheal diseases release
particularly large quantities of sodium and are therefore most likely to cause hyponatremia.
Drinking excess water sometimes causes hyponatremia, because the absorption of water into the bloodstream can dilute the sodium in the blood. This cause of
hyponatremia is rare, but has been found in psychotic
patients who compulsively drink more than 20 liters of
water per day. Excessive drinking of beer, which is
mainly water and low in sodium, can also produce
hyponatremia when combined with a poor diet.
Marathon running, under certain conditions,
leads to hyponatremia. Races of 25–50 miles can result
in the loss of great quantities (8 to 10 liters) of sweat,
which contains both sodium and water. Studies show
that about 30% of marathon runners experience mild
hyponatremia during a race. But runners who consume only pure water during a race can develop severe
hyponatremia because the drinking water dilutes the
sodium in the bloodstream. Such runners may experience neurological disorders as a result of the severe
hyponatremia and require emergency treatment.
Hyponatremia also develops from disorders in
organs that control the body’s regulation of sodium
or water. The adrenal gland secretes a hormone called
aldosterone that travels to the kidney, where it causes
the kidney to retain sodium by not excreting it into the
urine. Addison’s disease causes hyponatremia as a
result of low levels of aldosterone due to damage to
the adrenal gland. The hypothalamus and pituitary
gland are also involved in sodium regulation by making and releasing vasopressin, known as anti-diuretic
hormone, into the bloodstream. Like aldosterone,
vasopressin acts in the kidney, but it causes it to reduce
the amount of water released into urine. With more
vasopressin production, the body conserves water,
resulting in a lower concentration of plasma sodium.
Certain types of cancer cells produce vasopressin,
leading to hyponatremia.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Blood plasma and serum—Blood plasma, or
plasma, is prepared by obtaining a sample of
blood and removing the blood cells. The red
blood cells and white blood cells are removed by
spinning with a centrifuge. Chemicals are added to
prevent the blood’s natural tendency to clot. If
these chemicals include sodium, than a false measurement of plasma sodium content will result.
Serum is prepared by obtaining a blood sample,
allowing formation of the blood clot, and removing
the clot using a centrifuge. Both plasma and serum
are light yellow in color.

Symptoms of moderate hyponatremia include
tiredness, disorientation, headache, muscle cramps,
and nausea. Severe hyponatremia can lead to seizures and coma. These neurological symptoms are
thought to result from the movement of water into
brain cells, causing them to swell and disrupt their
functioning.
In most cases of hyponatremia, doctors are primarily concerned with discovering the underlying disease causing the decline in plasma sodium levels.
Death that occurs during hyponatremia is usually
due to other features of the disease rather than to the
hyponatremia itself.

Diagnosis
Hyponatremia is diagnosed by acquiring a blood
sample, preparing plasma, and using a sodium-sensitive electrode for measuring the concentration of
sodium ions. Unless the cause is obvious, a variety of
tests are subsequently run to determine if sodium was
lost from the urine, diarrhea, or from vomiting. Tests
are also used to determine abnormalities in aldosterone or vasopressin levels. The patient’s diet and use of
diuretics must also be considered.

Treatment
Severe hyponatremia can be treated by infusing a
solution of 5% sodium chloride in water into the
bloodstream. Moderate hyponatremia due to use of
diuretics or an abnormal increase in vasopressin is
often treated by instructions to drink less water each
day. Hyponatremia due to adrenal gland insufficiency
is treated with hormone injections.
1925

Hyponatremia

bloodstream. Diuretic drugs that frequently cause
hyponatremia include furosemide (Lasix), bumetanide
(Bumex), and most commonly, the thiazides. Diuretics
enhance the excretion of sodium into the urine, with
the goal of correcting high blood pressure. However,
too much sodium excretion can result in hyponatremia. Usually only mild hyponatremia occurs in
patients taking diuretics, but when combined with a
low sodium diet or with the excessive drinking of
water, severe hyponatremia can develop.

Hypoparathyroidism

Prognosis
Hyponatremia is just one manifestation of a variety of disorders. While hyponatremia can easily be
corrected, the prognosis for the underlying condition
that causes it varies.

Prevention
Patients who take diuretic medications must be
checked regularly for the development of hyponatremia.
Resources

causing low calcium levels and possible convulsions
in the newborn. Symptoms in the advanced and continuous stages of hypoparathyroidism include splitting of the nails, inadequate tooth development and
mental retardation in children, and seizures.
Abnormal low levels of calcium result in irritability of nerves, causing numbness and tingling of the
hands and feet, with painful-cramp like muscle spasms
known as tetany. Laryngeal spasms may also occur
causing respiratory obstruction.

Diagnosis

PERIODICALS

Fried, L. F., and P. M. Palevsky. ‘‘Hyponatremia and
Hypernatremia.’’ Medical Clinics of North America
81 (1997): 585-609.

Tom Brody, PhD

Hypoparathyroidism
Definition
Hypoparathyroidism is the result of a decrease
in production of parathyroid hormones by the parathyroid glands located behind the thyroid glands in
the neck. The result is a low level of calcium in the
blood.

Description
Parathyroid glands consist of four pea-shaped
glands located on the back and side of the thyroid
gland. The gland produces parathyroid hormone
which, along with vitamin D and calcitonin, are
important for the regulation of the calcium level in
the body. Hypoparathyroidism affects both males and
females of all ages.

Diagnostic measures begin with the individual’s
own observation of symptoms. A thorough medical
history and physical examination by a physician is
always required for an accurate diagnosis. The general
practitioner may refer the individual to an endocrinologist, a medical specialist who studies the function
of the parathyroid glands as well as other hormone
producing glands. Laboratory studies include blood
and urine tests to help determine phosphate and calcium levels. X rays are useful to determine any
abnormalities in bone density associated with abnormal calcium levels. These autoimmune disorders may
accompany hypoparathyroidism, but are not an
actual cause of it.

Treatment
In the event of severe muscle spasms, hospitalization may be warranted for calcium injections. Raising
carbon-dioxide levels in the blood, which can decrease
muscle spasms, may be achieved in immediate situations by placing a paper bag over the mouth and
blowing into it to ‘‘reuse’’ each breath. It is critical to
obtain timely periodic laboratory tests to check calcium levels. A high calcium, low-phosphorous diet
may be of significance and is directed by the physician
or dietitian.

Prognosis
Causes and symptoms
The accidental removal of the parathyroid glands
during neck surgery is the most frequent cause of
hypoparathyroidism. Complications of surgery on
the parathyroid glands is another common cause of
this disorder. There is the possibility of autoimmune
genetic disorders causing hypoparathyroidism such as
Hashimoto’s thyroiditis, pernicious anemia, and
Addison’s disease. The destruction of the gland by
radiation is a rare cause of hypoparathyroidism.
Occasionally, the parathyroids are absent at birth
1926

Presently hypoparathyroidism is considered
incurable. The disorder requires lifelong replacement
therapy to control symptoms. Medical research however, continues to search for a cure.

Prevention
There are no specific preventive measures for
hypoparathyroidism. However, careful surgical techniques are critical to reduce the risk of damage to the
gland during surgery.
GALE ENCYCLOPEDIA OF MEDICINE

Addison’s disease—A disease caused by partial or
total failure of adrenocortical (relating to, or
derived from the adrenal gland) function, which is
characterized by a bronze-like pigmentation of the
skin and mucous membranes, anemia, weakness,
and low blood pressure.
Autoimmunity—A condition by which the body’s
defense mechanism attacks itself.
Calcitonin—A hormone produced by the thyroid
gland in human beings that lowers plasma calcium
and phosphate levels without increasing calcium
accumulation.
Hashimoto’s thyroiditis—The self destruction of
the thyroid cells from an autoimmune disorder.
Hormones—A substance produced by one tissue
and conveyed by the bloodstream to another to affect
physiological activity, such as growth or metabolism.
Pernicious anemia—A severe anemia most often
affecting older adults, caused by failure of the stomach to absorb vitamin B12 and characterized by
abnormally large red blood cells, gastrointestinal
disturbances, and lesions of the spinal cord.

Resources
ORGANIZATIONS

American Medical Association. 515 N. State St., Chicago, IL
60612. (312) 464-5000. <http://www.ama-assn.org>.

Jeffrey P. Larson, RPT

could be suppressed only by removing their source, the
glands that made them. After the gonads were removed,
some cancers continued to grow, so other stimulants to
their growth had to removed. At this point, some cancer
specialists turned to the pituitary.
With the development of new therapeutic agents
and methods, especially new ways to manipulate hormones without removing their source, this type of
endocrine surgery has been largely relegated to history. However, tumors develop in the pituitary gland
that require removal. Here, the idea is to remove the
tumor but partially preserve the gland.

Description
There are several surgical approaches to the pituitary. The surgeon will choose the best one for the
specific procedure. The pituitary lies directly behind
the nose, and access through the nose or the sinuses is
often the best approach. Opening the skull and lifting
the frontal lobe of the brain will expose the delicate
neck of the pituitary gland. This approach works best
if tumors have extended above the pituitary fossa (the
cavity in which the gland lies).
Newer surgical methods using technology have
made other approaches possible. Stereotaxis is a threedimensional aiming technique using x rays or scans for
guidance. Instruments can be placed in the brain with
pinpoint accuracy through tiny holes in the skull. These
instruments can then manipulate brain tissue, either to
destroy it or remove it. Stereotaxis is also used to direct
radiation with similar precision using a gamma knife.
Access to some brain lesions can be gained through the
blood vessels using tiny tubes and wires guided by x rays.

Preparation

Hypophysectomy
Definition
Hypophysectomy or hypophysis is the removal of
the pituitary gland.

Purpose
The pituitary gland is in the middle of the head.
Removing this master gland is a drastic step that was
taken in the extreme circumstance of two cancers that
had escaped all other forms of treatment. Cancers of the
female breast and male prostate grow faster in the presence of sex hormones. It used to be that sex hormones
GALE ENCYCLOPEDIA OF MEDICINE

Pituitary surgery is performed by neurosurgeons
deep inside the skull. All the patient can do to prepare
is keep as healthy as possible and trust that the surgeon
will do his usual excellent job. Informed surgical consent is important so that the patient is fully confident
of the need for surgery and the expected outcome.

Aftercare
Routine post-operative care is required. In addition, pituitary function will be assessed.

Risks
The risks of surgery are multiple. Procedures are
painstakingly selected to minimize risk and maximize
benefit. Unique to surgery on the pituitary is the risk of
1927

Hypophysectomy

KEY TERMS

Hypopituitarism

KEY TERMS
Endocrine system—Group of glands and parts of
glands that control metabolic activity. Pituitary,
thyroid, adrenals, ovaries, and testes are all part of
the endocrine system.
Hormone—A chemical made in one place that has
effects in distant places in the body. Hormone production is usually triggered by the pituitary gland.

destroying the entire gland and leaving the entire endocrine system without guidance. This used to be the
whole purpose of hypophysectomy. After the procedure, the endocrinologist, a physician specializing in
the study and care of the endocrine system, would provide the patient with all the hormones needed. Patients
with no pituitary function did and still do quite well
because of the available hormone replacements.

Normal results
Complete removal of the pituitary was the goal for
cancer treatment. Today, removal of tumors with
preservation of the gland is the goal.

Abnormal results
Tumors may not be completely removed, due to
their attachment to vital structures.
Resources

function. The pituitary gland is located at the base of
the brain. Patients diagnosed with hypopituitarism
may be deficient in one single hormone, several hormones, or have complete pituitary failure.

Description
The pituitary is a pea-sized gland located at the
base of the brain, and surrounded by bone. The
hypothalamus, another endocrine organ in the brain,
controls the function of the pituitary gland by providing ‘‘hormonal orders.’’ In turn, the pituitary gland
regulates the many hormones that control various
functions and organs within the body. The posterior
pituitary acts as a sort of storage area for the hypothalamus and passes on hormones that control function
of the muscles and kidneys. The anterior pituitary
produces its own hormones which help to regulate
several endocrine functions.
In hypopituitarism, something interferes with the
production and release of these hormones, thus affecting the function of the target gland. Commonly
affected hormones may include:
Gonadotropin deficiency
Gonadotropin deficiency involves two distinct
hormones affecting the reproductive system.
Luteinizing hormone (LH) stimulates the testes in
men and the ovaries in women. This deficiency can
affect fertility in men and women and menstruation in
women. Follicle-stimulating hormone (FSH) has similar effects to LH.

BOOKS

Biller, Beverly M. K., and Gilbert H. Daniels.
‘‘Neuroendocrine Regulation and Diseases of the
Anterior Pituitary and Hypothalamus.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony S.
Fauci, et al. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Hypopigmentation see Albinism; Vitiligo

Hypopituitarism
Definition
Hypopituitarism is loss of function in an endocrine gland due to failure of the pituitary gland to
secrete hormones which stimulate that gland’s
1928

Thyroid stimulating hormone deficiency
Thyroid stimulating hormone (TSH) is involved
in stimulation of the thyroid gland. A lack of stimulation in the gland leads to hypothyroidism.
Adrenocorticotopic hormone deficiency
Also known as corticotropin, adrenocorticotopic
hormone (ACTH) stimulates the adrenal gland to
produce a hormone similar to cortisone, called cortisol. The loss of this hormone can lead to serious
problems.
Growth hormone deficiency
Growth hormone (GH) regulates the body’s
growth. Patients who lose supply of this hormone
before physical maturity will suffer impaired growth.
Loss of the hormone can also affect adults.
GALE ENCYCLOPEDIA OF MEDICINE

Prolactin stimulates the female breast to produce
milk. A hormone produced by the posterior pituitary,
antidiuretic hormone (ADH), controls the function of
the kidneys. When this hormone is deficient, diabetes
insipidus can result. However, patients with hypopituitarism rarely suffer ADH deficiency, unless the hypopituitarism is the result of hypothalamus disease.
Multiple hormone deficiencies
Deficiency of a single pituitary hormone occurs
less commonly than deficiency of more than one hormone. Sometimes referred to as progressive pituitary
hormone deficiency or partial hypopituitarism, there
is usually a predictable order of hormone loss.
Generally, growth hormone is lost first, then luteinizing hormone deficiency follows. The loss of folliclestimulating hormone, thyroid stimulating hormone
and adrenocorticotopic hormones follow much later.
The progressive loss of pituitary hormone secretion is
usually a slow process, which can occur over a period
of months or years. Hypopituitarism does occasionally start suddenly with rapid onset of symptoms.
Panhypopituitarism
This condition represents the loss of all hormones
released by the anterior pituitary gland. Panhypopituitarism is also known as complete pituitary failure.

Causes and symptoms
There are three major mechanisms which lead to
the development of hypopituitarism. The first involves
decreased release of hypothalamic hormones that
stimulate pituitary function. The cause of decreased
hypothalamic function may be congenital or acquired
through interference such as tumors, inflammation,
infection, mass lesions or interruption of blood supply. A second category of causes is any event or mass
which interrupts the delivery of hormones from the
hypothalamus. These may include particular tumors
and aneurysms. Damage to the pituitary stalk from
injury or surgery can also lead to hypopituitarism.
The third cause of hypopituitarism is damage to
the pituitary gland cells. Destroyed cells can not produce the pituitary hormones that would normally be
secreted by the gland. Cells may be destroyed by a
number of tumors and diseases. Hypopituitarism is
often caused by tumors, the most common of which
is pituitary adenoma.
Symptoms of hypopituitarism vary with the
affected hormones and severity of deficiency.
GALE ENCYCLOPEDIA OF MEDICINE

Frequently, patients have had years of symptoms
that were nonspecific until a major illness or stress
occurred. Overall symptoms may include fatigue, sensitivity to cold, weakness, decreased appetite, weight
loss and abdominal pain. Low blood pressure, headache and visual disturbances are other associated
symptoms.
Gonadotropin deficiency
Symptoms specific to this hormone deficiency
include decreased interest in sex for women and infertility in women and men. Women may also have premature cessation of menstruation, hot flashes, vaginal
dryness and pain during intercourse. Women who are
postmenopausal will not have obvious symptoms such
as these and may first present with headache or loss of
vision. Men may also suffer sexual dysfunction as a
result of gonadotropin deficiency. In acquired gonadotropin deficiency, both men and women may notice loss
of body hair.
Thyroid stimulating hormone deficiency
Intolerance to cold, fatigue, weight gain, constipation and pale, waxy and dry skin indicate thyroid
hormone deficiency.
Adrenocorticotopic hormone deficiency
Symptoms of ACTH deficiency include fatigue,
weakness, weight loss and low blood pressure.
Nausea, pale skin and loss of pubic and armpit hair
in women may also indicate deficiency of ACTH.
Growth hormone deficiency
In children, growth hormone deficiency will result
in short stature and growth retardation. Symptoms
such as obesity and skin wrinkling may or may not
show in adults and normal release of growth hormone
normally declines with age.
Other hormone deficiencies
Prolactin deficiency is rare and is the result of
partial or generalized anterior pituitary failure.
When present, the symptom is absence of milk production in women. There are no known symptoms for
men. ADH deficiency may produce symptoms of diabetes insipidus, such as excessive thirst and frequent
urination.
Multiple hormone deficiencies
Patients with multiple hormone deficiencies will
show symptoms of one or more specific hormone
1929

Hypopituitarism

Other hormone deficiencies

Hypopituitarism

deficiencies or some of the generalized symptoms
listed above.
Panhypopituitarism
The absence of any pituitary function should
show symptoms of one or all of the specific hormone
deficiencies. In addition to those symptoms, patients
may have dry, pale skin that is finely textured. The face
may appear finely wrinkled and contain a disinterested
expression.

Diagnosis
Once the diagnosis of a single hormone deficiency
is made, it is strongly recommended that tests for other
hormone deficiencies be conducted.
Gonadotropin deficiency
The detection of low levels of gonadotropin can
be accomplished through simple blood tests which
measure luteinizing hormone and follicle-stimulating
hormone, simultaneously with gonadal steroid levels.
The combination of results can indicate to a physician
if the cause of decreased hormone levels or function
belongs to hypopituitarism or some sort of primary
gonadal failure. Diagnosis will vary among men and
women.
Thyroid stimulating hormone deficiency
Laboratory tests measuring thyroid function can
help determine a diagnosis of TSH deficiency. The
commonly used tests are T4 and TSH measurement
done simultaneously to determine the reserve, or pool,
of thyroid-stimulating hormone.

measure growth factors that are dependent on growth
hormones. Sleep and exercise studies may also be used
to test for growth hormone deficiency, since these activities are known to stimulate growth hormone secretion.
Several drugs also induce secretion of growth hormone
and may be given to measure hormone response. The
standard test for growth hormone deficiency is the
insulin-induced hypoglycemia test. This test does
carry some risk from the induced hypoglycemia.
Other tests include an arginine infusion test, clonidine
test and growth-hormone releasing hormone test.
Other hormone deficiencies
If a test calculates normal levels of prolactin, deficiency of the hormone is eliminated as a diagnosis. A
TRH (thyrotropin-releasing hormone) simulation test
can determine prolactin levels. A number of tests are
available to detect ADH levels and to determine diagnosis of diabetes insipidus.
Multiple and general hypopituitarism tests
Physicians should be aware that nonspecific
symptoms can indicate deficiency of one or more hormones and should conduct a thorough clinical history.
In general, diagnosis of hypopituitarism can be
accomplished with a combination of dynamic tests
and simple blood tests, as well as imaging exams.
Most of these tests can be conducted in an outpatient
lab or radiology facility. Magnetic resonance imaging
(MRI) exams with gadolinium contrast enhancement
are preferred imaging exams to study the region of the
hypothalamus and pituitary gland. When MRI is not
available, a properly conducted computed tomography scan (CT scan) exam can take its place. These
exams can demonstrate a tumor or other mass, which
may be interfering with pituitary function.

Adrenocorticotopic hormone deficiency
An insulin tolerance test may be given to determine if cortisol levels rise when hypoglycemia is
induced. If they do not rise, there is insufficient reserve
of cortisol, indicating an ACTH deficiency. If the
insulin tolerance test is not safe for a particular
patient, a glucagon test offers similar results. A CRH
(corticotropin-releasing hormone) test may also be
given. It involves injection of CRH to measure,
through regularly drawn blood samples, a resulting
rise in ACTH and cortisol. Other tests which stimulate
ACTH may be ordered.

Panhypopituitarism
The insulin-induced hypoglycemia, or insulin tolerance test, which is used to determine specific hormone deficiencies, is an excellent test to diagnose
panhypopituitarism. This test can reveal levels of
growth hormone, ACTH (cortisol) and prolactin deficiency. The presence of insufficient levels of all of these
hormones is a good indication of complete pituitary
failure. Imaging studies and clinical history are also
important.

Treatment
Growth hormone deficiency
Growth hormone deficiency is measured through
the use of insulin-like growth factor I tests, which
1930

Treatment differs widely, depending on the age
and sex of the patient, severity of the deficiency, the
number of hormones involved, and even the
GALE ENCYCLOPEDIA OF MEDICINE

Gonadotropin deficiency
Replacement of gonadal steroids is common
treatment for LH and FSH deficiency. Estrogen for
women and testosterone for men will be prescribed in
the lowest effective dosage possible, since there can be
complications to this therapy. To correct women’s loss
of libido, small doses of androgens may be prescribed.
To restore fertility in men, regular hormone injections
may be required. Male and female patients whose
hypopituitarism results from hypothalamic disease
may be successfully treated with a hypothalamic releasing hormone (GnRH), which can restore gonadal function and fertility.
Thyroid stimulating hormone deficiency
In patients who have hypothyroidism, the function of the adrenal glands will be tested and treated
with steroids before administering thyroid hormone
replacement.
Adrenocorticotopic hormone deficiency
Hydrocortisone or cortisone in divided doses may
be given to replace this hormone deficiency. Most
patients require 20 mg or less of hydrocortisone per day.
Growth hormone deficiency
It is essential to treat children suffering from
growth hormone deficiency. The effectiveness of
growth hormone therapy in adults, particularly elderly
adults, is not as well documented. It is thought to help
restore normal muscle to fat ratios. Growth hormone
is an expensive and cautiously prescribed treatment.
Treatment of multiple deficiencies
and panhypopituitarism
The treatment of hypopituitarism is usually very
straightforward, but must normally continue for the
remainder of the patient’s life. Some patients may
receive treatment with GnRH, the hypothalamic hormone. In most cases, treatment will be based on the
specific deficiency demonstrated. Patients with hypopituitarism should be followed regularly to measure treatment effectiveness and to avoid overtreatment with
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Adenoma—A benign (not threatening or cancerous) tumor that originates in a gland.
Androgen—A hormone that usually stimulates the
sex hormones of the male.
Congenital—Present at birth.
Diabetes insipidus—A disorder originating in the
pituitary gland which is characterized by excessive
thirst and urination.
Endocrine—Refers to the system of internal secretion of substances into the body system from glands.
Hypoglycemia—Abnormal decrease of sugar in the
blood.
Hypothyroidism—Deficient activity of the thyroid
gland and resulting loss of energy.

hormone therapy. If the cause of the disorder is a
tumor or lesion, radiation or surgical removal are treatment options. Successful removal may reverse the hypopituitarism. However, even after removal of the mass,
hormone replacement therapy may still be necessary.

Prognosis
The prognosis for most patients with hypopituitarism is excellent. As long as therapy is continued,
many experience normal life spans. However, hypopituitarism is usually a permanent condition and prognosis depends on the primary cause of the disorder. It
can be potentially life threatening, particularly when
acute hypopituitarism occurs as a result of a large
pituitary tumor. Morbidity from the disease has
increased, although the cause is not known. It is possible that increased morbidity and death are due to
overtreatment with hormones. Any time that recovery
of pituitary function can occur is preferred to lifelong
hormone therapy.

Prevention
There is no known prevention of hypopituitarism,
except for prevention of damage to the pituitary/
hypothalamic area from injury.
Resources
ORGANIZATIONS

Alliance for Genetic Support Groups. 35 Wisconsin Circle,
Suite 440. Chevy Chase, MD 20815-7015. <http://
www.medhelp.org/geneticalliance>.
1931

Hypopituitarism

underlying cause of the hypopituitarism. Immediate
hormone replacement is generally administered to
replace the specific deficient hormone. Patient education is encouraged to help patients manage the impact
of their hormone deficiency on daily life. For instance,
certain illnesses, accidents or surgical procedures may
have adverse complications due to hypopituitarism.

Hypospadias and epispadias

Human Growth Foundation. 997 Glen Cove Ave., Glen
Head, NY 11545. (800) 451-6434. <http://
www.hgfound.org>.

Foreskin

OTHER

HealthAnswers.com <http://www.healthanswers.com>.
Urethral
opening

Teresa Norris, RN

Hypoplastic anemia see Aplastic anemia

Hypospadias and epispadias
Definition
Hypospadias is a congenital defect, primarily of
males, in which the urethra opens on the underside
(ventrum) of the penis. It is one of the most common
congenital abnormalities in the United States, occurring in about one of every 125 live male births. The
corresponding defect in females is an opening of the
urethra into the vagina and is rare.
Epispadias (also called bladder exstrophy) is a
congenital defect of males in which the urethra opens
on the upper surface (dorsum) of the penis. The corresponding defect in females is a fissure in the upper wall
of the urethra and is quite rare.

Description
In a male, the external opening of the urinary tract
(external meatus) is normally located at the tip of the
penis. In a female, it is normally located between the
clitoris and the vagina.
In males with hypospadias, the urethra opens on
the inferior surface or underside of the penis. In
females with hypospadias, the urethra opens into the
cavity of the vagina.
In males with epispadias, the urethra opens on the
superior surface or upper side of the penis. In females
with epispadias, there is a crack or fissure in the wall of
the urethra and out of the body through an opening in
the skin above the clitoris.
During the embryological development of males,
a groove of tissue folds inward and then fuses to form
a tube that becomes the urethra. Hypospadias occurs
when the tube does not form or does not fuse completely. Epispadias is due to a defect in the tissue that
folds inward to form the urethra.
During the development of a female, similar processes occur to form the urethra. The problem usually
1932

In hypospadias, the urethra opens along the penile shaft
rather than at the penile tip. (Illustration by Argosy Inc.)

is insufficient length of the tube that becomes the
urethra. As a result, the urethra opens in an abnormal
location, resulting in a hypospadias. Occasionally, fissures form in the bladder. These may extend to the
surface of the abdomen and fuse with the adjacent
skin. This most often is identified as a defect in the
bladder although it is technically an epispadias.
Hypospadias in males generally occur alone.
Female hypospadias may be associated with abnormalities of the genital tract, since the urinary and genital
tracts are formed in the same embryonic process.
Because it represents incomplete development of
the penis, some experts think that insufficient male
hormone may be responsible for hypospadias.
In males, the incidence of hypospadias is approximately one per 250 to 300 live births. Epispadias is
much less common, having an incidence of about one
per 100,000 live male births.
In females, hypospadias is much less common
than in males. It appears about once in every 500,000
live female births. Epispadias is even rarer. Reliable
estimates of the prevalence of epispadias in females are
not available. Epispadias in females is often diagnosed
and recorded as a bladder anomaly.

Causes and symptoms
Hypospadias and epispadias are congenital
defects of the urinary tract. This means they occur
during intrauterine development. There is no genetic
basis for the defects. Specific causes for hypospadias
are not known. This means that blood relatives do not
have increased chances of developing them. Reports
have shown some rise in prevalence of hypospadias
among offspring of mothers who work in certain
GALE ENCYCLOPEDIA OF MEDICINE

Concern was once raised that use of the antihistamine loratadine (Claritin) early in pregnancy might
cause hypospadias. However, a national clinical trial
revealed in 2004 that there was no link between the
drug and risk of second- or third-degree hypospadias.
Hypospadias usually is not associated with other
defects of the penis or urethra. In males, it can occur at
any site along the underside of the penis. In females,
the urethra exits the body in an abnormal location.
This usually is due to inadequate length of the urethra.
Epispadias is associated with bladder abnormalities. In females, the front wall of the bladder does not
fuse or close. The bladder fissure may extend to the
external abdominal wall. In such a rare case, the front
of the pelvis also is widely separated. In males, the
bladder fissure extends into the urethra and simply
becomes an opening somewhere along the upper
surface of the penis.
Hypospadias is associated with difficulty in
assigning gender to babies. This occurs when gender
is not obvious at birth because of deformities in the sex
organs.

Diagnosis
Male external urinary tract defects are discovered
at birth during the first detailed examination of the
newborn. Female urethral defects may not be discovered for some time due to the difficulty in viewing the
infant vagina.

Treatment
Surgery is the treatment of choice for both hypospadias and epispadias. All surgical repairs should be
undertaken early and completed without delay. This
minimizes psychological trauma.
In males with hypospadias, one surgery usually is
sufficient to repair the defect. With more complicated
hypospadias (more than one abnormally situated urethral opening), multiple surgeries may be required. In
females with hypospadias, surgical repair technically
is more complicated but can usually be completed in a
brief interval of time.
GALE ENCYCLOPEDIA OF MEDICINE

Repairing an epispadias is more difficult. In males,
this may involve other structures in the penis. Males
should not be circumcised since the foreskin often is
needed for the repair. Unfortunately, choices may be
required that affect the ability to inseminate a female
partner. Reproduction requires that the urethral meatus be close to the tip of the penis. Cosmetic appearance and ability to urinate (urinary continence) usually
are the primary goals. Surgery for these defects is successful 70 to 80% of the time. Modern treatment of
complete male epispadias allows for an excellent genital
appearance and achievement of urinary continence.
In females, repair of epispadias may require multiple surgical procedures. Urinary continence and
cosmetic appearance are the usual primary considerations. Urinary continence usually is achieved although
cosmetic appearance may be somewhat compromised.
Fertility is not usually affected. Repair rates that are
similar or better than those for males usually can be
achieved for females.
Hypospadias in both males and females is more of
a nuisance and hindrance to reproduction than a threat
to health. If surgery is not an option, the condition may
be allowed to persist. This usually leads to an increased
risk of infections in the lower urinary tract.

Prognosis
With adequate surgical repair, most males with
simple hypospadias can lead normal lives with a penis
that appears and functions in a normal manner. This
includes fathering children. Females with simple
hypospadias also have normal lives, including conceiving and bearing children.
The prognosis for epispadias depends on the
extent of the defect. Most males with relatively minor
epispadias lead normal lives, including fathering children. As the extent of the defect increases, surgical
reconstruction generally is acceptable. However,
many of these men are unable to conceive children.
Most epispadias in females can be surgically repaired.
The chances of residual disfigurement increase as the
extent of the epispadias increases. Fertility in females
is not generally affected by epispadias.
In hypospadias, the urethra opens along the penile
shaft rather than at the penile tip.
Resources
BOOKS

Nelson, Waldo E., et al., editors. ‘‘Anomalies of the
Bladder’’ In Nelson Textbook of Pediatrics.
Philadelphia: W. B. Saunders, 2000, pp. 1639-1642.
1933

Hypospadias and epispadias

occupations where they may be exposed to chemicals
that disrupt the endocrine system. However, a large
trial ending in 2003 showed that aside from a slight
increased risk among women who were hairdressers
from 1992-1996, there is no evidence that maternal
occupation or certain chemical exposure increases
risk of hypospadias. The role of chemicals in the development of the defect remains uncertain.

Hypotension

KEY TERMS
Bladder—This is the organ that stores urine after it
flows out of the kidneys and through the ureters.
Circumcision—The surgical removal of the foreskin of the penis.
Continence—Normal function of the urinary bladder and urethra, allowing fluid flow during urination and completely stopping flow at other times.
External meatus—The external opening through
which urine and seminal fluid (in males only)
leave the body.
Genital tract—The organs involved in reproduction. In a male, they include the penis, testicles,
prostate and various tubular structures to transport
seminal fluid and sperm. In a female, they include
the clitoris, vagina, cervix, uterus, fallopian tubes
and ovaries.

<http://www.meddean.luc.edu/lumen/MedEd/urology/abnpendv.htm>.
‘‘Hypospadias.’’ Atlas of Congenital Deformities of the
External Genitalia. <http://www.atlasperovic.com/
contents/9.htm>.
‘‘Hypospadias.’’ Columbia Presbyterian Hospital. <http://
cpmcnet.cpmc.columbia.edu/dept/urology/pediatric/
hypospadias.html>.
‘‘Hypospadias.’’ University of Michigan. <http://
www.urology.med.umich.edu/clinic/pediatric/
hypospadias.html>.
Johns Hopkins University Pediatric Urology Center.
‘‘Epispadias.’’ Johns Hopkins Exstrophy Database.
<http://www.med.jhu.edu/pediurol/pediatric/
exstrophy/database/web4d.html>.
The Penis.com. <http://www.the-penis.com/
hypospadias.html>.
Society for Pediatric Urology. <http://www.spu.org/>.

L. Fleming Fallon, Jr., MD, PhD, DrPH
Teresa G. Odle

Urethra—The tubular portion of the urinary tract
connecting the bladder and external meatus
through which urine passes. In males, seminal
fluid and sperm also pass through the urethra.

Hypotension
Definition
Nelson, Waldo E., et al., editors. ‘‘Anomalies of the penis
and urethra’’ In Nelson Textbook of Pediatrics.
Philadelphia: W. B. Saunders, 2000, pp. 1645-1650.
PERIODICALS

Kubetin, Sally Koch. ‘‘Hypospadias, Loratidine Use in
Pregnacy: No Link.’’ Pediatric News July 2004.
‘‘Molecular Epidemiology of Hypospadias: Genetic and
Environmental Risk Factors.’’ Health & Medicine
Week December 15, 2003: 424.
Vrijheid, M., et al. ‘‘Risk of Hypospadias in Relation to
Maternal Occupational Exposure to Potential
Endocrine Disrupting Chemicals.’’ Occupational and
Environmental Medicine August 2003: 543–548.
ORGANIZATIONS

Association for the Bladder Exstrophy Community. PO Box
1472, Wake Forest, NC 27588-1472. (919) 624-9447.
<http://www.bladderexstrophy.com/support.htm>.
Hypospadias Association of America. 4950 S. Yosemite
Street, Box F2-156, Greenwood Village, CO 80111.
hypospadiasassn@yahoo.com. <http://
www.hypospadias.net>.
Support for Parents with Hypospadias Boys. <http://
clubs.yahoo.com/clubs/mumswithhypospadiaskids>.
University of California - San Francisco. <http://
itsa.ucsf.edu/uroweb/Uro/hypospadias/index.html>.
OTHER

Hatch, David A., MD. ‘‘Abnormal Development of the
Penis and Male Urethra.’’ Genitourinary Development.
1934

Hypotension is the medical term for low blood
pressure.

Description
The pressure of the blood in the arteries rises and
falls as the heart and muscles handle demands of daily
living, such as exercise, sleep and stress. Some healthy
people have blood pressure well below the average for
their age, even though they have a completely normal
heart and blood vessels. This is often true of athletes
who are in superior shape. The term ‘‘hypotension’’ is
usually used only when blood pressure has fallen so far
that enough blood can no longer reach the brain,
causing dizziness and fainting.

Causes and symptoms
Postural hypotension is the most common type of
low blood pressure. In this condition, symptoms
appear after a person sits up or stands quickly. In
normal people, the cardiovascular system must make
a quick adjustment to raise blood pressure slightly to
account for the change in position. For those with
postural hypotension, the blood pressure adjustment
is not adequate or it doesn’t happen. Postural hypotension may occur if someone is taking certain drugs
GALE ENCYCLOPEDIA OF MEDICINE

Many people have a chronic problem with low
blood pressure that is not particularly serious. This
may include people who require certain medications,
who are pregnant, have bad veins, or have arteriosclerosis (hardening of the arteries).
The most serious problem with low blood pressure occurs when there is a sudden drop, which can be
life-threatening due to widespread ischemia (insufficient supply of blood to an organ due to blockage in an
artery). This type of low blood pressure may be due to
a wide variety of causes, including:

KEY TERMS
Arteriosclerosis—A group of disorders that causes
thickening and loss of elasticity in artery walls.

those people with postural hypotension, a medication
adjustment may help prevent the problem. These individuals may find that rising more slowly, or getting out
of bed in slow stages, helps the problem. Low blood
pressure with no other symptoms does not need to be
treated.

Prognosis



trauma with extensive blood loss



serious burns



shock from various causes (e.g. anaphylaxis)



heart attack



adrenal failure (Addisonian crisis)

Low blood pressure as a result of injury or other
underlying condition can usually be successfully treated
if the trauma is not too extensive or is treated in time.
Less serious forms of chronic low blood pressure have a
good prognosis and do not require treatment.



cancer

Resources



severe fever

BOOKS



serious infection (septicemia)

Smeltzer, Suzanne C., and Brenda G. Bare. Brunner and
Suddarth’s Textbook of Medical and Surgical
Nursing. 8th ed. Philadelphia:Lippincott-Raven
Publishers, 1996.

Diagnosis
Blood pressure is a measure of the pressure in the
arteries created by the heart contracting. During the
day, a normal person’s blood pressure changes constantly, depending on activity. Low blood pressure
can be diagnosed by taking the blood pressure with a
sphygmomanometer. This is a device with a soft rubber cuff that is inflated around the upper arm until it’s
tight enough to stop blood flow. The cuff is then
slowly deflated until the health care worker, listening
to the artery in the arm with a stethoscope, can hear
the blood first as a beat forcing its way along the
artery. This is the systolic pressure. The cuff is then
deflated more until the beat disappears and the blood
flows steadily through the open artery; this gives the
diastolic pressure.
Blood pressure is recorded as systolic (higher) and
diastolic (lower) pressures. A healthy young adult has
a blood pressure of about 110/75, which typically rises
with age to about 140/90 by age 60 (a reading now
considered mildly elevated).

Treatment
Treatment of low blood pressure depends on the
underlying cause, which can usually be resolved. For
GALE ENCYCLOPEDIA OF MEDICINE

Carol A. Turkington

Hypothermia
Definition
Hypothermia, a potentially fatal condition,
occurs when body temperature falls below 95  F
(35  C).

Description
Although hypothermia is an obvious danger for
people living in cold climates, many cases have
occurred when the air temperature is well above the
freezing mark. Elderly people, for instance, have succumbed to hypothermia after prolonged exposure to
indoor air temperatures of 50–65  F (10–18.3  C). In
the United States, hypothermia is primarily an urban
phenomenon associated with alcoholism, drug addiction, mental illness, and cold—water immersion
1935

Hypothermia

or medicine for high blood pressure. It also happens to
diabetics when nerve damage has disrupted the
reflexes that control blood pressure.

Hypothermia

accidents. The victims are often homeless male alcoholics. Officially, 11,817 deaths were attributed to
hypothermia in the United States from 1979 to 1994,
but experts suspect that many fatal cases go unrecognized. Nearly half the victims were 65 or older, with
males dominating every age group. Nonwhites were
also overrepresented in the statistics. Among males 65
and older, nonwhites outnumbered whites by more
than four to one.

Causes and symptoms
Measured orally, a healthy person’s body temperature can fluctuate between 97  F (36.1  C) and
100  F (37.8  C). Survival depends on maintaining
temperature stability within this range by balancing
the heat produced by metabolism with the heat lost to
the environment through (for the most part) the skin
and lungs. When environmental or other changes
cause heat loss to outpace heat production, the brain
triggers physiological and behavioral responses to
restore the balance. The involuntary muscular activity
of shivering, for example, aids heat production by
accelerating metabolism. But if the cold stress is too
great and the body’s defenses are overwhelmed, body
temperature begins to fall. Hypothermia is considered
to begin once body temperature reaches 95  F (35  C),
though even smaller drops in temperature can have an
adverse effect.
Hypothermia is divided into two types: primary
and secondary. Primary hypothermia occurs when the
body’s heat-balancing mechanisms are working properly but are subjected to extreme cold, whereas secondary hypothermia affects people whose heat-balancing
mechanisms are impaired in some way and cannot
respond adequately to moderate or perhaps even mild
cold. Primary hypothermia typically involves exposure
to cold air or immersion in cold water. The cold air
variety usually takes at least several hours to develop,
but immersion hypothermia will occur within about an
hour of entering the water, since water draws heat away
from the body much faster than air does. In secondary
hypothermia, the body’s heat-balancing mechanisms
can fail for any number of reasons, including strokes,
diabetes, malnutrition, bacterial infection, thyroid disease, spinal cord injuries (which prevent the brain from
receiving crucial temperature-related information from
other parts of the body), and the use of medications and
other substances that affect the brain or spinal cord.
Alcohol is one such substance. In smaller amounts it
can put people at risk by interfering with their ability to
recognize and avoid cold-weather dangers. In larger
amounts it shuts down the body’s heat-balancing
mechanisms.
1936

Secondary hypothermia is often a threat to the
elderly, who may be on medications or suffering
from illnesses that affect their ability to conserve
heat. Malnutrition and immobility can also put the
elderly at risk. Some medical research suggests as well
that shivering and blood vessel narrowing—two of the
body’s defenses against cold—may not be triggered as
quickly in older people. For these and other reasons,
the elderly can, over a period of days or even weeks,
fall victim to hypothermia in poorly insulated homes
or other surroundings that family, friends, and caregivers may not recognize as life threatening. Another
risk for the elderly is the fact that hypothermia can
easily be misdiagnosed as a stroke or some other common illness of old age.
The signs and symptoms of hypothermia follow a
typical course, though the body temperatures at which
they occur vary from person to person depending on
age, health, and other factors. The impact of hypothermia on the nervous system often becomes apparent quite
early. Coordination, for instance, may begin to suffer as
soon as body temperature reaches 95  F (35  C). The
early signs of hypothermia also include cold and pale
skin and intense shivering; the latter stops between 90  F
(32.2  C) and 86  F (30  C). As body temperature continues to fall, speech becomes slurred, the muscles go
rigid, and the victim becomes disoriented and experiences eyesight problems. Other harmful consequences
include dehydration as well as liver and kidney failure.
Heart rate, respiratory rate, and blood pressure rise
during the first stages of hypothermia, but fall once the
90  F (32.2  C) mark is passed. Below 86  F (30  C) most
victims are comatose, and below 82  F (27.8  C) the
heart’s rhythm becomes dangerously disordered. Yet
even at very low body temperatures, people can survive
for several hours and be successfully revived, though
they may appear to be dead.

Diagnosis
Information on the patient’s prior health and
activities often helps doctors establish a correct diagnosis and treatment plan. Pulse, blood pressure, temperature, and respiration require immediate
monitoring. Because the temperature of the mouth is
not an accurate guide to the body’s core temperature,
readings are taken at one or two other sites, usually the
ear, rectum, or esophagus. Other diagnostic tools
include electrocardiography, which is used to evaluate
heart rhythm, and blood and urine tests, which provide several kinds of key information; a chest x ray is
also required. A computed tomography scan (CT
scan) or magnetic resonance imaging (MRI) may be
needed to check for head and other injuries.
GALE ENCYCLOPEDIA OF MEDICINE

Emergency medical help should be summoned
whenever a person appears hypothermic. The danger
signs include intense shivering; stiffness and numbness
in the arms and legs; stumbling and clumsiness; sleepiness, confusion, disorientation, amnesia, and irrational behavior; and difficulty speaking. Until
emergency help arrives, a victim of outdoor hypothermia should be brought to shelter and warmed by
removing wet clothing and footwear, drying the skin,
and wrapping him or her in warm blankets or a sleeping bag. Gentle handling is necessary when moving the
victim to avoid disturbing the heart. Rubbing the skin
or giving the victim alcohol can be harmful, though
warm drinks such as clear soup and tea are recommended for those who can swallow. Anyone who aids
a victim of hypothermia should also look for signs of
frostbite and be aware that attempting to rewarm a
frostbitten area of the body before emergency help
arrives can be extremely dangerous. For this reason,
frostbitten areas must be kept away from heat sources
such as campfires and car heaters.
Rewarming is the essence of hospital treatment
for hypothermia. How rewarming proceeds depends
on the body temperature. Different approaches are
used for patients who are mildly hypothermic (the
patient’s body temperature is 90–95  F [32.2–35  C]),
moderately hypothermic (86–90  F [30–32.2  C]), or
severely hypothermic (less than 86  F [30  C]). Other
considerations, such as the patient’s age or the condition of the heart, can also influence treatment choices.
Mild hypothermia is reversed with passive
rewarming. This technique relies on the patient’s own
metabolism to rewarm the body. Once wet clothing is
removed and the skin is dried, the patient is covered
with blankets and placed in a warm room. The goal is
to raise the patient’s temperature by 0.5–2  C an hour.
Moderate hypothermia is often treated first with
active external rewarming and then with passive
rewarming. Active external rewarming involves applying heat to the skin, for instance by placing the patient
in a warm bath or wrapping the patient in electric
heating blankets.
Severe hypothermia requires active internal
rewarming, which is recommended for some cases of
moderate hypothermia as well. There are several types
of active internal rewarming. Cardiopulmonary bypass,
in which the patient’s blood is circulated through a
rewarming device and then returned to the body, is
considered the best, and can raise body temperature
by 1–2  C every 3–5 minutes. However, many hospitals
are not equipped to offer this treatment. The alternative
is to introduce warm oxygen or fluids into the body.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Antibiotics—Substances used against microorganisms that cause infection.
Computed tomography—A process that uses x rays
to create three-dimensional images of structures
inside the body.
Esophagus—A muscular tube through which food
and liquids pass on their way to the stomach.
Insulin—A substance that regulates blood glucose
levels. Glucose is a sugar.
Magnetic resonance imaging—The use of electromagnetic energy to create images of structures
inside the body.
Metabolism—The chemical changes by which the
body breaks down food and other substances and
builds new substances necessary for life.
Nervous system—The system that transmits information, in the form of electrochemical impulses,
throughout the body. It comprises the brain, spinal
cord, and nerves.
Rectum—The lower section of the large intestine.
The intestines are part of the digestive system.
Stroke—A condition involving loss of blood flow to
the brain.
Thyroid—A gland (fluid-secreting structure) in the
neck. It plays an important role in metabolism.

Hypothermia treatment can also include, among
other things, insulin, antibiotics, and fluid replacement
therapy. When the heart has stopped, both cardiopulmonary resuscitation (CPR) and rewarming are necessary. Once a patient’s condition has stabilized, he or
she may need treatment for an underlying problem
such as alcoholism or thyroid disease.

Prognosis
Victims of mild or moderate hypothermia usually
enjoy a complete recovery. In regard to severely
hypothermic patients, the prognosis for survival varies
due to differences in people’s physiological responses
to cold.

Prevention
People who spend time outdoors in cold weather
can reduce heat loss by wearing their clothing
1937

Hypothermia

Treatment

Hypothyroidism

loosely and in layers and by keeping their hands,
feet, and head well covered (30–50% of body heat
is lost through the head). Because water draws heat
away from the body so easily, staying dry is important, and wet clothing and footwear should be
replaced as quickly as possible. Wind- and waterresistant outer garments are also crucial. Alcohol
should be avoided because it promotes heat loss by
expanding the blood vessels that carry body heat to
the skin.
Preventing hypothermia among the elderly
requires vigilance on the part of family, friends, and
caregivers. An elderly person’s home should be properly insulated and heated, with living areas kept at a
temperature of 70  F (21.1  C). Warm clothing and
bedding are essential, as are adequate food, rest, and
exercise; warming the bed and bedroom before going
to sleep is also recommended. Older people who live
alone should be visited regularly—at least once a day
during very cold weather—to ensure that their health
remains sound and that they are taking good care of
themselves. For help and advice, family members and
others can turn to government and social service agencies. Meals on wheels and visiting nurse programs, for
instance, may be available, and it may be possible to
obtain financial aid for winterizing and heating
homes.
Resources
BOOKS

Petty, Kevin J. ‘‘Hypothermia.’’ In Harrison’s Principles of
Internal Medicine, edited by Anthony S. Fauci, et al.
New York: McGraw-Hill, 1997.

Howard Baker

Hypothyroidism
Definition
Hypothyroidism, or underactive thyroid, develops when the thyroid gland fails to produce or secrete
as much thyroxine (T4) as the body needs. Because T4
regulates such essential functions as heart rate, digestion, physical growth, and mental development, an
insufficient supply of this hormone can slow lifesustaining processes, damage organs and tissues in
every part of the body, and lead to life-threatening
complications.
1938

Description
Hypothyroidism is one of the most common
chronic diseases in the United States. Symptoms may
not appear until years after the thyroid has stopped
functioning and they are often mistaken for signs of
other illnesses, menopause, or aging. Although this
condition is believed to affect as many as 11 million
adults and children, as many as two of every three
people with hypothyroidism may not know they have
the disease.
Nicknamed ‘‘Gland Central’’ because it influences almost every organ, tissue, and cell in the
body, the thyroid is shaped like a butterfly and
located just below the Adam’s apple. The thyroid
stores iodine the body gets from food and uses this
mineral to create T4. Low T 4 levels can alter weight,
appetite, sleep patterns, body temperature, sex drive,
and a variety of other physical, mental, and emotional characteristics.
There are three types of hypothyroidism. The
most common is primary hypothyroidism, in which
the thyroid doesn’t produce an adequate amount
of T4. Secondary hypothyroidism develops when
the pituitary gland does not release enough of the
thyroid-stimulating hormone (TSH) that prompts
the thyroid to manufacture T4. Tertiary hypothyroidism results from a malfunction of the
hypothalamus, the part of the brain that controls
the endocrine system. Drug-induced hypothyroidism, an adverse reaction to medication, occurs in
two of every 10,000 people, but rarely causes severe
hypothyroidism.
Hypothyroidism is at least twice as common in
women as it is in men. Although hypothyroidism is
most common in women who are middle-aged or
older, the disease can occur at any age. Newborn
infants are tested for congenital thyroid deficiency
(cretinism) using a test that measures the levels
of thyroxine in the infant’s blood. Treatment within
the first few months of life can prevent mental
retardation and physical abnormalities. Older children who develop hypothyroidism suddenly stop
growing.
Factors that increase a person’s risk of developing
hypothyroidism include age, weight, and medical history. Women are more likely to develop the disease
after age 50; men, after age 60. Obesity also increases
risk. A family history of thyroid problems or a personal history of high cholesterol levels or such autoimmune diseases as lupus, rheumatoid arthritis, or
diabetes can make an individual more susceptible to
hypothyroidism.
GALE ENCYCLOPEDIA OF MEDICINE



progressive hearing loss

Hypothyroidism is most often the result of
Hashimoto’s disease, also known as chronic thyroiditis
(inflammation of the thyroid gland). In this disease, the
immune system fails to recognize that the thyroid gland
is part of the body’s own tissue and attacks it as if it
were a foreign body. The attack by the immune system
impairs thyroid function and sometimes destroys the
gland. Other causes of hypothyroidism include:



weight gain



problems with memory and concentration



depression



goiter (enlarged thyroid gland)



muscle pain or weakness



loss of interest in sex

Radiation. Radioactive iodine used to treat
hyperthyroidism (overactive thyroid) or radiation
treatments for head or neck cancers can destroy the
thyroid gland.



numb, tingling hands



dry skin



swollen eyelids



dryness, loss, or premature graying of hair



extreme sensitivity to cold



constipation



irregular menstrual periods



hoarse voice







Surgery. Removal of the thyroid gland because of
cancer or other thyroid disorders can result in
hypothyroidism.
Viruses and bacteria. Infections that depress thyroid
hormone production usually cause permanent
hypothyroidism.



Medication. Nitroprusside, lithium, or iodides can
induce hypothyroidism. Because patients who use
these medications are closely monitored by their
doctors, this side effect is very rare.



Pituitary gland malfunction. This is a rare condition
in which the pituitary gland fails to produce enough
TSH to activate the thyroid’s production of T4.



Congenital defect. One of every 4,000 babies is born
without a properly functioning thyroid gland.



Diet. Because the thyroid makes T4 from iodine
drawn from food, an iodine-deficient diet can cause
hypothyroidism. Adding iodine to table salt and
other common foods has eliminated iodine deficiency in the United States. Certain foods (cabbage,
rutabagas, peanuts, peaches, soybeans, spinach) can
interfere with thyroid hormone production.



Environmental contaminants. Certain man-made
chemicals—such as PCBs—found in the local environment at high levels may also cause hypothyroidism.

Hypothyroidism is sometimes referred to as a
‘‘silent’’ disease because early symptoms may be so
mild that no one realizes anything is wrong.
Untreated symptoms become more noticeable and
severe, and can lead to confusion and mental disorders,
breathing difficulties, heart problems, fluctuations in
body temperature, and death.
Someone who has hypothyroidism will probably
have more than one of the following symptoms:


fatigue



decreased heart rate

GALE ENCYCLOPEDIA OF MEDICINE

Hypothyroidism

Causes and symptoms

Hypothyroidism usually develops gradually.
When the disease results from surgery or other treatment for hyperthyroidism, symptoms may appear suddenly and include severe muscle cramps in the arms,
legs, neck, shoulders, and back.
It’s important to see a doctor if any of these
symptoms appear unexpectedly. People whose
hypothyroidism remains undiagnosed and untreated
may eventually develop myxedema. Symptoms of this
rare but potentially deadly complication include
enlarged tongue, swollen facial features, hoarseness,
and physical and mental sluggishness.
Myxedema coma can cause unresponsiveness;
irregular, shallow breathing; and a drop in blood
pressure and body temperature. The onset of this
medical emergency can be sudden in people who are
elderly or have been ill, injured, or exposed to very cold
temperatures; who have recently had surgery; or who
use sedatives or anti-depressants. Without immediate
medical attention, myxedema coma can be fatal.

Diagnosis
Diagnosis of hypothyroidism is based on the
patient’s observations, medical history, physical
examination, and thyroid function tests. Doctors
who specialize in treating thyroid disorders (endocrinologists) are most apt to recognize subtle symptoms
and physical indications of hypothyroidism. A blood
test known as a thyroid-stimulating hormone (TSH)
assay, thyroid nuclear medicine scan, and thyroid
ultrasound are used to confirm the diagnosis. A
woman being tested for hypothyroidism should let
1939

Hypothyroidism

her doctor know if she is pregnant or breastfeeding
and all patients should be sure their doctors are aware
of any recent procedures involving radioactive materials or contrast media.
The TSH assay is extremely accurate, but some
doctors doubt the test’s ability to detect mild
hypothyroidism. They advise patients to monitor
their basal (resting) body temperature for below-normal readings that could indicate the presence of
hypothyroidism.

Treatment
Natural or synthetic thyroid hormones are used to
restore normal (euthyroid) thyroid hormone levels.
Synthetic hormones are more effective than natural
substances, but it may take several months to determine the correct dosage. Patients start to feel better
within 48 hours, but symptoms will return if they stop
taking the medication.
Most doctors prescribe levothyroxine sodium
tablets, and most people with hypothyroidism will
take the medication for the rest of their lives. Aging,
other medications, and changes in weight and general
health can affect how much replacement hormone a
patient needs, and regular TSH tests are used to monitor hormone levels. Patients should not switch from
one brand of thyroid hormone to another without a
doctor’s permission.

KEY TERMS
Cretinism—Severe hypothyroidism that is present
at birth.
Endocrine system—The network of glands that produce hormones and release them into the bloodstream. The thyroid gland is part of the endocrine
system.
Hypothalamus—The part of the brain that controls
the endocrine system.
Myxedema—A condition that can result from a
thyroid gland that produces too little of its hormone. In addition to a decreased metabolic rate,
symptoms may include anemia, slow speech, an
enlarged tongue, puffiness of the face and hands,
loss of hair, coarse and thickened skin, and sensitivity to cold.
Pituitary gland—Small, oval endocrine gland
attached to the hypothalamus. The pituitary gland
releases TSH, the hormone that activates the thyroid gland.
Thyroid-stimulating hormone (TSH)—A hormone
secreted by the pituitary gland that controls the
release of T4 by the thyroid gland.
Thyroxine (T4)—Thyroid hormone that regulates
many essential body processes.

Regular exercise and a high-fiber diet can help
maintain thyroid function and prevent constipation.

Alternative treatment
Alternative treatments are primarily aimed at
strengthening the thyroid and will not eliminate
the need for thyroid hormone medications. Herbal
remedies to improve thyroid function and relieve
symptoms of hypothyroidism include bladder wrack
(Fucus vesiculosus), which can be taken in capsule
form or as a tea. Some foods, including cabbage,
peaches, radishes, soybeans, peanuts, and spinach,
can interfere with the production of thyroid hormones. Anyone with hypothyroidism may want to
avoid these foods. The Shoulder Stand yoga position
(at least once daily for 20 minutes) is believed to
improve thyroid function.

Prognosis
Thyroid hormone replacement therapy generally
maintains normal thyroid hormone levels unless treatment is interrupted or discontinued.
1940

Prevention
Primary hypothyroidism can’t be prevented, but
routine screening of adults could detect the disease in
its early stages and prevent complications.
Resources
ORGANIZATIONS

American Thyroid Association. Montefiore
Medical Center, 111 E. 210th St.,
Bronx, NY 10467.
Endocrine Society. 4350 East West Highway, Suite 500,
Bethesda, MD 20814-4410. (301) 941-0200.
Thyroid Foundation of America, Inc. Ruth Sleeper Hall,
RSL 350, Boston, MA 02114-2968. (800) 832-8321 or
(617) 726-8500.
Thyroid Society for Education and Research. 7515 S. Main
St., Suite 545, Houston, TX 77030. (800) THYROID or
(713) 799-9909.

Maureen Haggerty
GALE ENCYCLOPEDIA OF MEDICINE

Hypotonic duodenography
Definition
Hypotonic duodenography is an x-ray procedure
that produces images of the duodenum. The duodenum is the first part of the small intestine.

Purpose
Hypotonic duodenography may be ordered to
detect tumors of the head of the pancreas or the
area where the pancreatic and bile ducts meet the
small intestine. Lesions causing upper abdominal
pain may be demonstrated by duodenography, and
the procedure can aid in the diagnosis of chronic
pancreatitis.

Precautions
Some patients with narrowing of the tubes in the
upper gastrointestinal tract should not receive duodenography. Patients with certain heart disorders and
glaucoma are cautioned against receiving an agent
called anticholinergic, which is administered during
the procedure to lessen intestinal muscle spasms. A
hormone called glucagon may also be used to relax
the intestines, but its use is not recommended in
patients with most forms of diabetes.

Description
Hypotonic duodenography is also referred to as
x ray of the duodenum or simply as duodenography.
The patient is seated while the radiologist places a
catheter in the nose and down into the stomach.
Then the patient lies down and the tube is continued
to the duodenum. The radiologist is guided in this
placement by a fluoroscopic image. (Fluoroscopic
equipment shows an immediate x ray. In this case,
the x ray shows the location of the catheter as it is
moved into the stomach and duodenum.) Next, either
the glucagon is administered intravenously or anticholinergic is injected into the patient to relax the
muscles of the intestine.
After several minutes, the physician will administer barium through the catheter. Barium is a contrast
agent that will help highlight the area on the fluoroscopy screen and x rays. After a few films are taken,
some of the barium is withdrawn and air is sent in
through the catheter. Additional images are acquired
and the catheter is then removed. The procedure takes
from 30–60 minutes.
GALE ENCYCLOPEDIA OF MEDICINE

Patients are required to fast from midnight before
the test until after the test, or about 6–12 hours. Just
prior to the exam, patients should remove dentures,
glasses, and other objects that may interfere with the
procedure. The patient may be instructed to empty his
or her bladder just prior to duodenography.

Aftercare
The barium should be expelled within two to three
days. Extra fluids and/or an agent given by the physician to help encourage bowel movement may aid in
barium elimination. Physicians and patients should
watch for possible reactions to the anticholinergic or
glucagon. If an anticholinergic is used, patients are
advised to empty their bladder within a few hours
after the exam and to wait two hours for clearing of
vision or have someone drive them home. Patients will
notice that their stools are chalky white from the
barium for one to three days following the procedure.

Risks
Abdominal cramping may occur when the physician instills air into the duodenum, but aside from the
discomfort, there are few risks associated with this
procedure. Side effects from the contrast, hormones
or agents may occur. Those patients with diabetes,
heart disease, or glaucoma run the highest risk of
reaction and should not receive anticholinergic or glucagon, depending on their specific conditions. Elderly
patients or those who are extremely ill, must be closely
monitored during the procedure for possible return of
fluid, or gastric reflux.

Normal results
The linings of the duodenum and surrounding
tissues will look smooth and even. The shape of the
head of the pancreas will appear normal and near the
duodenal wall.

Abnormal results
Any masses or irregular nodules on the wall of the
duodenum may indicate tumors or abnormality of
tissue. Tumors of the head of the pancreas or of the
opening into the intestine from the pancreatic and bile
ducts may be seen. Chronic pancreatitis may be indicated on the x rays. In many instances, follow-up
laboratory or imaging studies may be ordered to
further study the abnormal findings and confirm a
diagnosis.
1941

Hypotonic duodenography

Preparation

Hysterectomy

menstruation stops and a woman loses the ability to
bear children.

KEY TERMS
Anticholinergic—A drug that lessens muscle
spasms in the intestines, lungs, bladder, and eye
muscles.
Fluoroscopic (fluoroscopy)—An x-ray procedure
that produces immediate images and motion on a
screen. The images look like those seen at airport
baggage security stations.
Glucagon—A hormone that changes glycogen, a
carbohydrate stored in muscles and the liver, into
glucose. It can be used to relax muscles for a procedure such as duodenography.
Pancreas—A five-inch-long gland that lies behind
the stomach and next to the duodenum. The pancreas releases glucagon, insulin and some of the
enzymes which aid digestion. Pancreatitis is the
swelling of the pancreas which can nausea, jaundice, and severe pain and may be fatal.

Resources
ORGANIZATIONS

American College of Radiology. 1891 Preston White Drive,
Reston, VA 22091. (800) 227-5463. <http://
www.acr.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Teresa Odle

Hypovolemic shock see Shock

Hysterectomy
Definition
Hysterectomy is the surgical removal of the
uterus. In a total hysterectomy, the uterus and cervix
are removed. In some cases, the fallopian tubes and
ovaries are removed along with the uterus (called
hysterectomy with bilateral salpingo-oophorectomy).
In a subtotal hysterectomy, only the uterus is
removed. In a radical hysterectomy, the uterus, cervix,
ovaries, oviducts, lymph nodes, and lymph channels
are removed. The type of hysterectomy performed
depends on the reason for the procedure. In all cases,
1942

Purpose
Hysterectomy is the second most common operation performed in the United States. About 556,000 of
these surgeries are done annually. By age 60, approximately one out of every three American women will
have had a hysterectomy. Yet it’s estimated that
30 percent of hysterectomies are unnecessary.
About 10% of hysterectomies are performed to
treat cancer of the cervix, ovaries, or uterus. Women
with cancer in one or more of these organs almost
always have the organ(s) removed as one part of
their cancer treatment.
The most frequent reason for hysterectomy in the
United States is to remove fibroid tumors, accounting
for 30% of these surgeries. Fibroid tumors are noncancerous (benign) growths in the uterus, which can
cause pelvic and low back pain and heavy or lengthy
menstrual periods. They occur in 30–40% of women
over age 40, and are three times more likely to be
present in African-American women than in
Caucasian women. Fibroids do not need to be
removed unless they are causing symptoms that interfere with a woman’s normal activities.
Treatment of endometriosis is the reason for 20%
of hysterectomies. The endometrium is the lining of
the uterus. Endometriosis is a condition that occurs
when the cells from the endometrium begin growing
outside the uterus. The outlying endometrial cells
respond to the hormones that control the menstrual
cycle, bleeding each month the way the lining of the
uterus does. This causes irritation of the surrounding
tissue, leading to pain and scarring.
Another 20% percent of hysterectomies are done
because of heavy or abnormal vaginal bleeding that
can not be linked to any specific cause and cannot be
controlled by other means. The remaining 20% of
hysterectomies are performed to treat prolapsed
uterus, pelvic inflammatory disease, and endometrial
hyperplasia, a potentially precancerous condition.

Alternatives
There are several alternatives to hysterectomy
today. They include:
Embolization
Uterine artery embolization is not a surgical procedure. Instead, interventional radiologists put a
GALE ENCYCLOPEDIA OF MEDICINE

Myomectomy
A myomectomy is a surgery used to remove
fibroids, thus avoiding a hysterectomy. Hysteroscopic
myomectomy, in which a surgical ‘‘telescope,’’ or
laparascope, is inserted into the uterus through the
vagina can be done on an outpatient basis. If there are
large fibroids, however, an abdominal incision is
required. Then women typically are hospitalized for
two to three days, and require up to six weeks recovery.
However, laparascopic myomectomies are also being
done more often. They only require three small incisions in the abdomen, and have a much shorter hospitalization and recovery time.
Once the fibroids have been removed, the surgeon
must repair the wall of the uterus to eliminate future
bleeding or infection.
Endometrial ablation
In this surgical procedure, recommended for
women with small fibroids, the entire lining of the
uterus is removed. Women are no longer fertile,
however. The uterine cavity is filled with fluid and a
hysteroscopy, or telescope, inserted to provide a clear
view of the uterus. Then the uterus is destroyed using
a laser beam or electric voltage. The procedure is
typically done under anesthesia, although women
can go home the same day as the surgery. Another,
newer procedure involves using a balloon, which is
filled with superheated liquid and inflated until it
fills the uterus. The liquid kills the lining, and after
8 minutes the balloon is removed.

performed in the case of uterine and cervical cancer.
This is the most common kind of hysterectomy.
Sometimes, in addition to a total hysterectomy a
procedure called a bilateral salpingo-oophorectomy is
performed. This surgery removes the ovaries and the
fallopian tubes. Removal of the ovaries eliminates the
main source of the hormone estrogen, so menopause
occurs immediately. Removal of the ovaries and fallopian tubes is performed in about one-third of hysterectomy operations, often to reduce the risk of ovarian
cancer.
Subtotal hysterectomy
If the reason for the hysterectomy is to remove
uterine fibroids, treat abnormal bleeding, or relieve
pelvic pain, it may be possible to remove only the
uterus and leave the cervix. This procedure, called a
subtotal hysterectomy (or partial hysterectomy),
removes the least amount of tissue. The opening to
the cervix is left in place. Some women feel that leaving
the cervix intact aids in their achieving sexual satisfaction. This procedure, which used to be rare, is now
performed more frequently when requested.
Subtotal hysterectomy is easier to perform than a
total hysterectomy, but leaves a woman at risk for
cervical cancer. She will still need to get yearly pap
smears.
Radical hysterectomy
Radical hysterectomies are performed on women
with cervical cancer or endometrial cancer that has
spread to the cervix. A radical hysterectomy removes
the uterus, cervix, top part of the vagina, ovaries,
fallopian tubes, lymph nodes, lymph channels, and
tissue in the pelvic cavity that surrounds the cervix.
This type of hysterectomy removes the most tissue and
requires the longest hospital stay and longer recovery
period.

Precautions
Endometrial resection
Like endometrial ablation, the uterine lining is
also destroyed during this procedure, only instead of
a laser, an electrosurgical wire loop is used.
Total hysterectomy
A total hysterectomy, sometimes called a simple
hysterectomy, removes the entire uterus and the cervix. The ovaries are not removed and continue to
secrete hormones. Total hysterectomies are always
GALE ENCYCLOPEDIA OF MEDICINE

The frequency with which hysterectomies are performed in the United States has been questioned in
recent years. It has been suggested that a large number
of hysterectomies are performed unnecessarily. The
United States has the highest rate of hysterectomies
(number of hysterectomies per thousand women) of
any country in the world. Also, the frequency of this
surgery varies across different regions of the United
States. Rates are highest in the South and Midwest,
and are higher for African American women. In recent
years, although the number of hysterectomies
1943

Hysterectomy

catherter into the artery that leads to the uterus and
inject polyvinyl alcohol particles right where the artery
leads to the blood vessels that nourish the fibroids. By
killing off those blood vessels, the fibroids have no
more blood supply, and they die off. Severe cramping
and pain after the procedure is common, but serious
complications are less than 5 percent and it may protect fertility.

Hysterectomy

Fallopian tube

Ovary

Uterus
Cervix
Vagina
Subtotal hysterectomy

Total hysterectomy

Total hysterectomy with
salpingo-oophorectomy

Three types of hysterectomies: subtotal, total, and total with salpingo-oophorectomy. (Illustration by Electronic Illustrators Group.)

performed has declined, the number of hysterectomies
performed on younger women in their 30s and 40s is
increasing, and 55 percent of all hysterectomies are
performed on women 35 to 49.
Women for whom a hysterectomy is recommended should discuss possible alternatives with
their doctor and consider getting a second opinion,
since this is major surgery with life-changing implications. Alternative treatments exist for many conditions. Whether these alternatives are appropriate for
any individual woman is a decision she and her doctor
should make together.
As in all major surgery, the health of the patient
affects the risk of the operation. Women who have
chronic heart or lung diseases, diabetes, or irondeficiency anemia may not be good candidates for
this operation. Heavy smoking, obesity, use of steroid
drugs, and use of illicit drugs add to the surgical risk.

Description
There are two ways that hysterectomies can be
performed. The choice of method depends on the
type of hysterectomy, the doctor’s experience, and
the reason for the hysterectomy.
Abdominal hysterectomy
About 75% of hysterectomies performed in the
United States are abdominal hysterectomies. The
surgeon makes a four to six inch incision either horizontally across the pubic hair line from hip bone to hip
bone or vertically from navel to pubic bone. Horizontal
incisions leave a less noticeable scar, but vertical incisions give the surgeon a better view of the abdominal
cavity. The blood vessels, fallopian tubes, and ligaments are cut away from the uterus, which is lifted out.
1944

Abdominal hysterectomies take from one to three
hours. The hospital stay is three to five days, and it
takes four to eight weeks to return to normal activities.
The advantages of an abdominal hysterectomy
are that the uterus can be removed even if a woman
has internal scarring (adhesions) from previous surgery
or her fibroids are large. The surgeon has a good view
of the abdominal cavity and more room to work. Also,
surgeons have the most experience with this type of
hysterectomy. The abdominal incision is more painful
than with vaginal hysterectomy and the recovery period is longer.
Vaginal hysterectomy
With a vaginal hysterectomy, the surgeon makes
an incision near the top of the vagina. The surgeon
then reaches through this incision to cut and tie off the
ligaments, blood vessels, and fallopian tubes. Once
the uterus is cut free, it is removed through the vagina.
The operation takes one to two hours. The hospital
stay is usually one to three days, and return to normal
activities takes about four weeks.
The advantages of this procedure are that it leaves
no visible scar and is less painful. The disadvantage is
that it is more difficult for the surgeon to see the uterus
and surrounding tissue. This makes complications
more common. Large fibroids cannot be removed
using this technique. It is very difficult to remove the
ovaries during a vaginal hysterectomy, so this
approach may not be possible if the ovaries are
involved.
Vaginal hysterectomy can also be performed
using a laparoscopic technique. With this surgery, a
tube containing a tiny camera is inserted through an
incision in the navel. This allows the surgeon to see the
uterus on a video monitor. The surgeon then inserts
GALE ENCYCLOPEDIA OF MEDICINE

This technique, called laparoscopic-assisted
vaginal hysterectomy, allows surgeons to perform a
vaginal hysterectomy that might be too difficult otherwise. The hospital stay is usually only one day.
Recovery time is about two weeks. The disadvantage
is that this operation is relatively new and requires
great skill by the surgeon.
Any vaginal hysterectomy may have to be converted to an abdominal hysterectomy during surgery if
complications develop.

KEY TERMS
Cervix—The lower part of the uterus extending into
the vagina.
Fallopian tubes—Slender tubes that carry eggs
(ova) from the ovaries to the uterus.
Lymph nodes—Small, compact structures lying
along the channels that carry lymph, a yellowish
fluid. Lymph nodes produce white blood cells
(lymphocytes), which are important in forming
antibodies that fight disease.
Prolapsed uterus—A uterus that has slipped out of
place, sometimes protruding down through the
vagina.

Preparation
Before surgery the doctor will order blood and
urine tests. The woman may also meet with the
anesthesiologist to evaluate any special conditions
that might affect the administration of anesthesia.
On the evening before the operation, the woman
should eat a light dinner and then avoid eating or
drinking anything.

Aftercare
After surgery a woman will feel pain. The degree
of discomfort varies, and is generally greatest in
abdominal hysterectomies because of the incision.
Hospital stays vary from about two days (laparoscopic-assisted vaginal hysterectomy) to five or
six days (abdominal hysterectomy with bilateral
salpingo-oophorectomy). During the hospital stay, the
doctor will probably order more blood tests.
Return to normal activities such as driving and
working takes anywhere from two to eight weeks,
again depending on the type of surgery. Some
women have emotional changes following a hysterectomy. Women who have had their ovaries removed
will probably start taking hormone replacement
therapy.

Risks
Hysterectomy is a relatively safe operation,
although like all major surgery it carries risks. These
include unanticipated reaction to anesthesia, internal
bleeding, blood clots, damage to other organs such as
the bladder, and post-surgery infection. The risk of
death is about one in every 1,000 (1/1,000) women
having the operation.
GALE ENCYCLOPEDIA OF MEDICINE

Other complications sometimes reported after a
hysterectomy include changes in sex drive, weight
gain, constipation, and pelvic pain. Hot flashes and
other symptoms of menopause can occur if the ovaries
are removed. Women who have both ovaries removed
and who do not take estrogen replacement therapy run
an increased risk for heart disease and osteoporosis (a
condition that causes bones to be brittle). Women with
a history of psychological and emotional problems
before the hysterectomy are more likely to experience
psychological difficulties after the operation.

Normal results
Although there is some concern that hysterectomies may be performed unnecessarily, there are
many conditions for which the operation improves a
woman’s quality of life. In the Maine Woman’s Health
Study, 71% of women who had hysterectomies to
correct moderate or severe painful symptoms reported
feeling better mentally, physically, and sexually after
the operation.
Resources
ORGANIZATIONS

American Cancer Society. (800) 227-2345.<http://
www.cancer.org>.
National Cancer Institute. (800) 4-CANCER.<http://
www.nci.nih.gov>.
OTHER

Parker, William H. ‘‘A Gynecologist’s Second Opinion.’’
<http://www.gynsecondopinion.com>.

Debra Gordon
1945

Hysterectomy

two slender instruments through small incisions in the
abdomen and uses them to cut and tie off the blood
vessels, fallopian tubes, and ligaments. When the
uterus is detached, it is removed though a small incision at the top of the vagina.

Hysteria

Histrionic personality disorder

Hysteria
Definition
The term ‘‘hysteria’’ has been in use for over 2,000
years and its definition has become broader and more
diffuse over time. In modern psychology and psychiatry, hysteria is a feature of hysterical disorders in
which a patient experiences physical symptoms that
have a psychological, rather than an organic, cause;
and histrionic personality disorder characterized by
excessive emotions, dramatics, and attention-seeking
behavior.

According to the Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition (DSMIV ), individuals with histrionic personality possess at
least five of the following symptoms or personality
features:


a need to be the center of attention



inappropriate, sexually seductive, or provocative
behavior while interacting with others



rapidly changing emotions and superficial expression of emotions



vague and impressionistic speech (gives opinions
without any supporting details)



easily influenced by others



believes relationships are more intimate than they
are.

Description
Hysterical disorders
Patients with hysterical disorders, such as conversion and somatization disorder experience physical
symptoms that have no organic cause. Conversion
disorder affects motor and sensory functions, while
somatization affects the gastrointestinal, nervous,
cardiopulmonary, or reproductive systems. These
patients are not ‘‘faking’’ their ailments, as the symptoms are very real to them. Disorders with hysteric
features typically begin in adolescence or early
adulthood.
Histrionic personality disorder
Histrionic personality disorder has a prevalence of
approximately 2–3% of the general population. It
begins in early adulthood and has been diagnosed
more frequently in women than in men. Histrionic
personalities are typically self-centered and attention
seeking. They operate on emotion, rather than fact or
logic, and their conversation is full of generalizations
and dramatic appeals. While the patient’s enthusiasm,
flirtatious behavior, and trusting nature may make
them appear charming, their need for immediate gratification, mercurial displays of emotion, and constant
demand for attention often alienates them from others.

Causes and symptoms
Hysterical disorders
Hysteria may be a defense mechanism to avoid
painful emotions by unconsciously transferring this
distress to the body. There may be a symbolic function
for this, for example a rape victim may develop paralyzed legs. Symptoms may mimic a number of physical
and neurological disorders which must be ruled out
before a diagnosis of hysteria is made.
1946

Diagnosis
Hysterical disorders frequently prove to be
actual medical or neurological disorders, which
makes it important to rule these disorders out
before diagnosing a patient with hysterical disorders.
In addition to a patient interview, several clinical
inventories may be used to assess the patient for
hysterical tendencies, such as the Minnesota
Multiphasic Personality Inventory-2 (MMPI-2) or
the Millon Clinical Multiaxial Inventory-III
(MCMI-III). These tests may be administered in an
outpatient or hospital setting by a psychiatrist or
psychologist.

Treatment
Hysterical disorders
For people with hysterical disorders, a supportive
healthcare environment is critical. Regular appointments with a physician who acknowledges the
patient’s physical discomfort are important.
Psychotherapy may be attempted to help the patient
gain insight into the cause of their distress. Use of
behavioral therapy can help to avoid reinforcing
symptoms.
Histrionic personality disorder
Psychotherapy is generally the treatment of choice
for histrionic personality disorder. It focuses on
supporting the patient and on helping develop the
skills needed to create meaningful relationships with
others.
GALE ENCYCLOPEDIA OF MEDICINE

Hysteria

J E A N M A R T I N C H A R C O T (1825–1893)
a professor of pathological anatomy until 1862, when he
was named senior physician at the Salpêtrière, a hospital
for the treatment of mental illness.
Charcot’s research and work on psychoneuroses
and hysterical disorders untimately helped to dispell
the belief that hysteria was a disorder found only in
women. Charcot also explored the possibility that physiological abnormalities of the nervous system played a
part when behavioral problems were exhibited. He
became known for his ability to diagnose and locate
these abnormalities of the central nervous system.
Finally, Charcot’s most notable contribution to the
field of psychiatry was his successful use of hypnotism
in the diagnosis and treatment of hysteria. He found
that, while hypnotized, the patient recalled details,
which were not readily available to the individual in a
conscious state. In addition, Charcot found that the
therapist could more easily influence the hypnotized
patient during therapy. In 1882, Charcot presented his
research findings to the French Academy of Sciences
with favorable results.
(Library of Congress.)

Jean Martin Charcot was born to a carriage maker on
November 29, 1825,in Paris, France. Charcot attended
the University of Paris, earning his medical degree in
1853. In 1860, he accepted a position at the university as

Charcot was a prolific writer and a talented artist.
Between 1888 and 1894, his complete works were compiled into nine volumes. His most noted work Lectures on
the Diseases of the Nervous System was published in 1877.
Charcot died on August 16, 1893.

Histrionic personality disorder

KEY TERMS
Conversion disorder—A psychological disorder
that alters motor or sensory functions. Paralysis,
blindness, anesthesia (lack of feeling), coordination
or balance problems, and seizures are all common
symptoms of the disorder.
Somatization disorder—The appearance of physical symptoms in the gastrointestinal system, the nervous system, the cardiopulmonary system, or the
reproductive system that have no organic cause.

Prognosis
Hysterical disorders
The outcome for hysterical disorders varies by
type. Somatization is typically a lifelong disorder,
while conversion disorder may last for months or
years. Symptoms of hysterical disorders may suddenly
disappear, only to reappear in another form later.
GALE ENCYCLOPEDIA OF MEDICINE

Individuals with histrionic personality disorder
may be at a higher risk for suicidal gestures, attempts,
or threats in an effort to gain attention. Providing a
supportive environment for patients with both hysterical disorders and histrionic personality disorder is key
to helping these patients.
Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.

Paula Anne Ford-Martin
1947

Hysterosalpingography

Hysterosalpingography
Definition
Hysterosalpingography is a procedure where
x rays are taken of a woman’s reproductive tract
after a dye is injected. Hystero means uterus and
salpingo means tubes, so hysterosalpingography
literally means to take pictures of the uterus and
fallopian tubes. This procedure may also be called
hysterography (or HSG).

Purpose
Hysterosalpingography is used to determine if
the fallopian tubes are open, or if there are any
apparent abnormalities or defects in the uterus. It
can be used to detect tumors, scar tissue, or tears in
the lining of the uterus. This procedure is often used
to help diagnose infertility in women. The fallopian
tubes are the location where an egg from the ovary
joins with sperm to produce a fertilized ovum. If the
fallopian tubes are blocked or deformed, the egg may
not be able to descend or the sperm may be blocked
from moving up to meet the egg. Up to 30% of all
cases of infertility are due to damaged or blocked
fallopian tubes.

Precautions
This procedure should not be done on women
who suspect they might be pregnant or who may
have a pelvic infection. Women who have had an
allergic reaction to dye used in previous x-ray procedures should inform their doctor.

Description
As with other types of pelvic examinations, the
woman will lie on her back on an examination table
with her legs sometimes raised in stirrups. The x-ray
equipment is placed above the abdomen.
A speculum is inserted into the vagina and a
catheter (a thin tube) is inserted into the uterus
through the cervix (the opening to the uterus). A
small balloon in the catheter is inflated to hold it in
place. A liquid water-based or oil-based dye is then
injected through the catheter into the uterus. This
process can cause cramping, pain, and uterine
spasms.
As the dye spreads through the reproductive tract,
the doctor may watch for blockages or abnormalities
on an x-ray monitor. Several x rays will also be taken.
1948

A hysterosalpingogram of the abdomen of a woman whose
fallopian tubes are blocked. The fallopian tube (right on
image) is blocked near the uterus, the triangular shape
at center. The other fallopian tube is obstructed at a
point further from the uterus where dilatation has occurred.
(Photo Researchers, Inc. Reproduced by permission.)

The procedure takes approximately 15–30 minutes.
The x rays will be developed while the patient waits,
but the final reading and interpretation of the x rays by
a radiologist (a doctor who specializes in x rays) may
not be available for a few days.
Interestingly, sometimes the hysterosalpingography procedure itself can be considered a treatment.
The dye used can sometimes open up small blockages
in the fallopian tubes. The need for additional test
procedures or surgical treatments to deal with infertility should be discussed with the doctor.

Preparation
This procedure is generally done in the x-ray
department of a hospital or large clinic. General anesthesia is not needed. A pain reliever may be taken prior to
the procedure to lessen the severity of cramping.

Aftercare
While no special aftercare is required after a
hysterosalpingography, the woman may be
observed for some period after the procedure to
ensure that she does not have any allergic reactions
to the dye. A sanitary napkin may be worn after
GALE ENCYCLOPEDIA OF MEDICINE

Catheter—A thin tube, usually made of plastic, that
is inserted into the body to allow the passage of
fluid into or out of a site.
Fallopian tubes—The narrow ducts leading from a
woman’s ovaries to the uterus. After an egg is
released from the ovary during ovulation, fertilization (the union of sperm and egg) normally occurs
in the fallopian tubes.
Hysterography—Another term for the x-ray procedure of the uterus and fallopian tubes.
Hysterosalpingogram—The term for the x ray taken
during a hysterosalpingography procedure.
Speculum—A plastic or stainless steel instrument
that is inserted into the opening of the vagina so the
cervix (the opening of the uterus) and interior of the
vagina can be examined.

the procedure to absorb dye that will flow out
through the vaginal opening. If a blockage is seen
in a tube, the patient may be given an antibiotic. A
woman should notify her doctor if she experiences
excessive bleeding, extensive pelvic pain, fever, or
an unpleasant vaginal odor after the procedure.
These symptoms may indicate a pelvic infection.
Counseling may be necessary to interpret the
results of the x rays, and to discuss any additional
procedures to treat tubal blockages or uterine
abnormalities found.

Risks
Cramps during the procedure are common. Complications associated with hysterosalpingography
include abdominal pain, pelvic infection, and allergic
reactions. It is also possible that abnormalities of the
fallopian tubes and uterus will not be detected by this
procedure.

Normal results
A normal hysterosalpingography will show a
healthy, normally shaped uterus and unblocked fallopian tubes.

Abnormal results
Blockage of one or both of the fallopian tubes or
abnormalities of the uterus may be detected.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Society for Reproductive Medicine. 1209
Montgomery Highway, Birmingham, AL 35216-2809.
(205) 978-5000. <http://www.asrm.com>.

Altha Roberts Edgren

Hysteroscopy
Definition
Hysteroscopy is a procedure that allows a physician to look through the vagina and neck of the uterus
(cervix) to inspect the cavity of the uterus. A telescopelike instrument called a hysteroscope is used.
Hysteroscopy is used as both a diagnostic and a treatment tool.

Purpose
Diagnostic hysteroscopy may be used to evaluate
the cause of infertility, to determine the cause of
repeated miscarriages, or to help locate polyps and
fibroids.
The procedure is also used to treat gynecological
conditions, often instead of or in addition to dilatation
and curettage (D&C). A D&C is a procedure for scraping the lining of the uterus. A D&C can be used to take
a sample of the lining of the uterus for analysis.
Hysteroscopy is an advance over D&C because the
doctor can take tissue samples of specific areas or actually see fibroids, polyps, or structural abnormalities.
When used for treatment, the hysteroscope is used
with other devices to remove polyps, fibroids, or IUDs
that have become embedded in the wall of the uterus.

Precautions
The procedure is not performed on women with
cervical cancer, endometrial cancer, or acute pelvic
inflammation.

Description
Diagnostic hysteroscopy is performed in either a
doctor’s office or hospital. Before inserting the hysteroscope, the doctor injects a local anesthetic around
the cervix. Once it has taken effect, the doctor dilates
the cervix and then inserts a narrow lighted tube (the
1949

Hysteroscopy

Resources

KEY TERMS

Hysteroscopy

Bladder
Hysteroscope
Uterus

Fibroids

Rectum
Hysteroscopy is a procedure that allows inspection of the uterus by using a telescope-like instrument called a hysteroscope.
(Illustration by Electronic Illustrators Group.)

hysteroscope) through the cervix to reveal the inside of
the uterus. Ordinarily, the walls of the uterus are
touching each other. In order to get a better view, the
uterus is inflated with carbon dioxide gas or fluid.
Hysteroscopy takes about 30 minutes, and can cost
anywhere from $750 to $4,000 depending on the extent
of the procedure.
Treatment involving the use of hysteroscopy is
usually performed as a day surgical procedure with
regional or general anesthesia. Tiny surgical instruments are inserted through the hysteroscope, and are
used to remove polyps or fibroids. A small sample of
tissue lining the uterus is often removed for examination, especially if there is any abnormal bleeding.

Preparation
If the procedure is done in the doctor’s office, the
patient will be given a mild pain reliever before
the procedure to ease cramping. The doctor will
wash the vagina and cervix with an antiseptic solution.
If the procedure is done in the hospital under
general anesthesia, the patient should not eat or
drink anything (not even water) after midnight the
night before the procedure.

Aftercare
Many women experience light bleeding for several
days after surgical hysteroscopy. Mild cramping or
1950

pain is common after operative hysteroscopy, but
usually fades away within eight hours. If carbon dioxide gas was used, there may also be some shoulder
pain. Nonprescription pain relievers may help ease
discomfort. Women may want to take the day off
and relax after having hysteroscopy.

Risks
Diagnostic hysteroscopy is a fairly safe procedure
that only rarely causes complications. The primary
risk is prolonged bleeding or infection, usually following surgical hysteroscopy to remove a growth.
Very rare complications include perforation of the
uterus, bowel, or bladder. Surgery under general
anesthesia causes the additional risks typically associated with anesthesia.
Patients should alert their health care provider if
they develop any of these symptoms:


abnormal discharge



heavy bleeding



fever over 101  F (38.3  C)



severe lower abdominal pain

Normal results
A normal, healthy uterus with no fibroids or other
growths.
GALE ENCYCLOPEDIA OF MEDICINE

women whose endometrium appears abnormal
during baseline ultrasound imaging

Fibroid—A benign tumor of the uterus



women with fertility problems. Infertility is sometimes related to polyps, leiomyomas (fibroids), or
adhesions inside the uterus. Adhesions are areas of
tissue that have grown together to form bands or
membranes across the inside of the uterus.



women receiving tamoxifen therapy for breast cancer

Polyp—A growth that projects from the lining of the
cervix, the nose, or any other mucus membrane.
Septum—A condition present at birth in which
there is an extra fold of tissue down the center of
the uterus that can cause infertility. This tissue
can be removed with a wire electrode and a
hysteroscope.

Abnormal results
Using hysteroscopy, the doctor may find uterine
fibroids or polyps (often the cause of abnormal bleeding) or a septum (extra fold of tissue down the center
of the uterus) that can cause infertility. Sometimes,
precancerous or malignant growths are discovered.
Resources

Hysterosonography is useful as a screening test
to minimize the use of more invasive diagnostic
procedures, such as tissue biopsies and dilation and
curettage (D&C). Hysterosonography can also be
used as a follow-up after uterine surgery to evaluate
its success.

Precautions
Hysterosonography is difficult to perform in
patients with certain abnormalities:


Cervical stenosis. Cervical stenosis means that the
lower end of the uterus is narrowed or tightened. It
complicates the insertion of a tube (catheter).



Adhesions or large fibroids. These growths sometimes block the flow of saline fluid into the uterus.

PERIODICALS

Anon. ‘‘Looking Inside the Uterus.’’ Harvard Women’s
Health Watch 4, no. 5 (January 1997): 4-5.

Carol A. Turkington

Hysterosonography
Definition
Hysterosonography, which is also called sonohysterography, is a new noninvasive technique that
involves the slow infusion of sterile saline solution
into a woman’s uterus during ultrasound imaging.
Hysterosonography allows the doctor to evaluate
abnormal growths inside the uterus; abnormalities
of the tissue lining the uterus (the endometrium); or
disorders affecting deeper tissue layers. Hysterosonography does not require either radiation or contrast
media, or invasive surgical procedures

Purpose
Hysterosonography is used to evaluate patients in
the following groups:


peri- or postmenopausal women with unexplained
vaginal bleeding

GALE ENCYCLOPEDIA OF MEDICINE

Patients with active pelvic inflammatory disease
(PID) should not be tested with hysterosonography
until the disease is brought under control. Women
with chronic PID or heart problems are given antibiotics before the procedure.

Description
A hysterosonography is preceded by a baseline
ultrasound examination performed through the
vagina. This allows the doctor to detect an unsuspected pregnancy and to assess the thickness and possible abnormalities of the patient’s endometrium. The
doctor then inserts a catheter into the uterus and
injects sterile saline fluid while ultrasound imaging is
recorded on film or videotape. The procedure takes
about 10 to 15 minutes.

Preparation
Patients do not require special preparation apart
from the timing of the procedure. Patients with fertility problems are examined during the first 10 days of
the menstrual cycle. Patients who may have polyps are
usually examined at a later phase in the cycle. The best
time for examining women with fibroids is still under
discussion.
1951

Hysterosonography



KEY TERMS

Hysterosonography

Aftercare

KEY TERMS
Adhesion—An abnormal union or attachment of
two areas of tissue.
Contrast medium—A chemical substance used to
make an organ or body part opaque on x ray.
Dilation and curettage (D&C)—A surgical procedure in which the patient’s cervix is widened
(dilated) and the endometrium is scraped with a
scoop-shaped knife (curette).

Aftercare consists of advising the patient to contact her doctor in case of abnormal bleeding, fever, or
abdominal pain. Some spotting or cramping is common, however, and can usually be treated with nonsteroidal anti-inflammatory drugs, such as ibuprofen.

Risks
The chief risks are mild spotting and cramping
after the procedure.

Endometrium—The tissue that lines the uterus.
Fibroid—Another word for leiomyoma.
Leiomyoma—A benign tumor composed of muscle
tissue. Leiomyomas in the uterus are sometimes
called fibroids.
Pelvic inflammatory disease (PID)—An inflammation of the fallopian tubes, usually caused by bacterial infection.
Polyp—A growth projecting from the lining of the
uterus. Polyps can cause fertility problems or
abnormal vaginal bleeding.
Saline solution—A solution of sterile water and salt
used in a variety of medical procedures. In hysterosonography, saline solution is used to fill the
uterus for diagnostic imaging.
Transvaginal ultrasound (US)—The diagnostic
imaging procedure that serves as the baseline for
a hysterosonographic examination.

Normal results
Normal findings include a symmetrical uterus
with a normal endometrium and no visible masses or
tumors.

Abnormal results
Abnormal findings include adhesions; polyps; leiomyomas; abnormal thickening of the endometrium; or
tissue changes related to tamoxifen (Nolvadex), which
is a drug given for breast cancer.
Resources
PERIODICALS

Cullinan, Joanne, et al. ‘‘Sonohysterography: A Technique
for Endometrial Evaluation.’’ RadioGraphics 15 (May
1995): 501-514.

Rebecca J. Frey, PhD

1952

GALE ENCYCLOPEDIA OF MEDICINE

I
IBS see Irritable bowel syndrome
Ibuprophen see Nonsteroidal
anti-inflammatory drugs

Both inherited and acquired ichthyoses affect
males and females equally.

Causes and symptoms
Inherited ichthyoses

Ichthyosis
Definition
Derived from two Greek words meaning ‘‘fish’’
and ‘‘disease,’’ ichthyosis is a congenital (meaning
present at birth) dermatological (skin) disease that is
represented by thick, scaly skin.

Description
The ichthyoses are a group of skin diseases caused
by an abnormality in skin growth that results in drying
and scaling. There are at least 20 types of ichthyosis.
Ichthyosis can be more or less severe, sometimes accumulating thick scales and cracks that are painful and
bleed. Ichthyosis is not contagious. Some forms of
ichthyosis are inherited while others are acquired in
later life as a symptom of systemic disorders.
The most common form of ichthyosis, accounting
for 95% of all cases of ichthyosis, is called ichthyosis
vulgaris (vulgaris is the Latin word for ‘‘common’’),
and occurs in approximately one person in every 250.
It is inherited in an autosomal dominant manner. The
most rare types of ichthyosis occur in fewer than one
person in one million and are inherited in an autosomal recessive manner. Ichthyosis occurs regardless of
the part of the world the child is from, or the ethnic
background of the parents.
Acquired ichthyosis is extremely rare; neither its
incidence in the United States nor its incidence in the
rest of the world are known as of 2003.
GALE ENCYCLOPEDIA OF MEDICINE

Depending on the specific type of ichthyosis, the
inheritance can be autosomal recessive, autosomal
dominant, X-linked recessive, X-linked dominant, or
sporadic. Autosomal recessive means that the altered
gene for the disease or trait is located on one of the first
22 pairs of chromosomes, which are also called ‘‘autosomes.’’ Males and females are equally likely to have
an autosomal recessive disease or trait. Recessive
means that two copies of the altered gene are necessary
to express the condition. Therefore, a child inherits
one copy of the altered gene from each parent, who
are called carriers (because they have only one copy of
the altered gene). Since carriers do not express the
altered gene, parents usually do not know they carry
the altered gene that causes ichthyosis until they have
an affected child. Carrier parents have a 1-in-4 chance
(or 25%) with each pregnancy, to have a child with
ichthyosis.
Autosomal dominant inheritance also means that
both males and females are equally likely to have the
disease but only one copy of the altered gene is necessary to have the condition. An individual with
ichthyosis has a 50/50 chance to pass the condition
to his or her child.
The skin is made up of several layers, supported
underneath by a layer of fat that is thicker or thinner
depending on location. The lower layers contain blood
vessels, the middle layers contain actively growing
cells, and the upper layer consists of dead cells that
serve as a barrier to the outside world. This barrier is
nearly waterproof and highly resistant to infection.
Scattered throughout the middle layers are hair
1953

Ichthyosis

follicles, oil and sweat glands, and nerve endings. The
upper layer is constantly flaking off and being
replaced from beneath by new tissue. In ichthyosis,
the skin’s natural shedding process is slowed or inhibited; and in some types, skin cells are produced too
rapidly.
The abnormality in skin growth and hydration
called ichthyosis may present with symptoms at birth
or in early childhood. Ichthyosis can itch relentlessly,
leading to such complications of scratching as lichen
simplex (dermatitis characterized by raw patches
of skin). Either the cracking or the scratching can
introduce infection, bringing with it discomfort and
complications.
Acquired ichthyoses
The mildest form of acquired ichthyosis is called
xeroderma, or dry flaky skin. It is not associated with
any systemic diseases. Xeroderma occurs most often
on the lower legs of middle-aged and elderly adults
during cold weather, or on the lower legs of people
who bathe too often. It is characterized chiefly by mild
or moderate itching.
Ichthyosis may also be an early symptom of such
disorders as AIDS, lymphoma, hypothyroidism, or
leprosy. In these cases the ichthyosis is most noticeable
on the patient’s trunk and legs.
A few rare cases of acquired ichthyosis have
been attributed to the use of certain drugs, specifically
cimetidine (Tagamet), triparanol (Metasqualene),
dixyrazine (a phenothiazine derivative used as an
antipsychotic), nicotinic acid (vitamin B3, butyrophenone antipsychotics (Haldol, Inapsine, Orap), and
clofazimine (Lamprene).

Diagnosis
A dermatologist will often make the diagnosis of
ichthyosis based on findings from a clinical examination. However, a skin biopsy, or DNA study (from a
small blood sample) is necessary to confirm the diagnosis. Evaluation for associated problems is done by a
complete physical medical examination.
For some types of ichythyosis, the abnormal gene
has been identified and prenatal testing is available. At
present this is true for the autosomal recessive congenital ichythoses, which include: lamellar ichthyosis
(LI), autosomal recessive lamellar ichthyosis (ARLI),
congenital ichthyosiform erythroderma (CIE), and
non-bullous congenital ichthyosiform erythroderma
(NBCIE).
1954

There are four different genes that have been
located for the autosomal recessive congenital
ichthyoses. Testing, however, is available for only
one gene, known as transglutaminase-1 (TGM1).
This gene is located on chromosome 14. Once a
couple has had a child with ichthyosis, and they
have had the genetic cause identified by DNA
studies (performed from a small blood sample),
prenatal testing for future pregnancies may be considered. (Note that prenatal testing may not be
possible if both mutations cannot be identified.)
Prenatal diagnosis is available via either chorionic
villus sampling (CVS) or amniocentesis. CVS is a
biopsy of the placenta performed in the first trimester of pregnancy under ultrasound guidance.
Ultrasound is the use of sound waves to visualize
the developing fetus. The genetic makeup of the
placenta is identical to the fetus and therefore the
TGM1 gene can be studied from this tissue. There
is approximately a one in 100 chance for miscarriage with CVS. Amniocentesis is a procedure done
under ultrasound guidance in which a long thin
needle is inserted through the mother’s abdomen
into the uterus, to withdraw a couple of tablespoons of amniotic fluid (fluid surrounding the
developing baby) to study. The TGM1 gene can
be studied using cells from the amniotic fluid.
Other genetic tests, such as a chromosome analysis,
may also be performed through either CVS or
amniocentesis.
Acquired ichthyosis is usually diagnosed in the
course of identifying the underlying disorder. With
the exception of acquired ichthyosis related to lymphoma, a doctor cannot tell the difference between
inherited and acquired ichthyosis by examining skin
samples through a microscope.

Treatment
Most treatments for ichthyosis are topical, which
means that they are applied directly to the skin, not
taken internally. Xeroderma is eaily treated by minimizing bathing and applying an emollient cream or
mineral oil after bathing while the skin is still moist.
Some forms of ichthyosis require two forms of treatment—a reduction in the amount of scale buildup and
moisturizing of the underlying skin. Several agents are
available for each purpose. Reduction in the amount
of scale is achieved by keratolytics. Among this class
of drugs are urea, lactic acid, and salicylic acid.
Petrolatum, 60% propylene glycol, and glycerin are
successful moisturizing agents, as are many commercially available products. Increased humidity of the
ambient air is also helpful in preventing skin dryness.
GALE ENCYCLOPEDIA OF MEDICINE

Amniocentesis—A procedure performed at 16–18
weeks of pregnancy in which a needle is inserted
through a woman’s abdomen into her uterus to
draw out a small sample of the amniotic fluid
from around the baby. Either the fluid itself or
cells from the fluid can be used for a variety of
tests to obtain information about genetic disorders
and other medical conditions in the fetus.
Amniotic fluid—The fluid that surrounds a developing baby during pregnancy.
Autosomal dominant—A pattern of genetic inheritance where only one abnormal gene is needed to
display the trait or disease.
Autosomal recessive inheritance—A pattern of
genetic inheritance where two abnormal genes
are needed to display the trait or disease.
Dermatologist—A physician that specializes in
diagnosing and treating disorders of the skin.
Emollients—Petroleum or lanolin-based skin
lubricants.
Keratin—A tough, nonwater-soluble protein found
in the nails, hair, and the outermost layer of skin.
Human hair is made up largely of keratin.
Keratinocytes—Skin cells.
Keratolytic—An agent that dissolves or breaks
down the outer layer of skin (keratins).
Retinoids—A derivative of synthetic Vitamin A.
Sporadic—Isolated or appearing occasionally with
no apparent pattern.
X-linked dominant inheritance—The inheritance
of a trait by the presence of a single gene on the
X chromosome in a male or female, passed from an
affected female who has the gene on one of her
X chromosomes.
X-linked recessive inheritance—The inheritance of
a trait by the presence of a single gene on the
X chromosome in a male, passed from a female
who has the gene on one of her X chromosomes,
and who is referred to as an unaffected carrier.

Because the skin acts as a barrier to the outside
environment, medicines have a hard time penetrating,
especially through the thick skin of the palms of the
hands and the soles of the feet. This resistance is
diminished greatly by maceration (softening the
skin). Soaking hands in water macerates skin so that
it looks like prune skin. Occlusion (covering) with
GALE ENCYCLOPEDIA OF MEDICINE

rubber gloves or plastic wrap will also macerate skin.
Applying medicines and then covering the skin with an
occlusive dressing will facilitate entrance of the medicine and greatly magnify its effect.
Secondary treatments are necessary to control
pruritus (itching) and infection. Commercial products
containing camphor, menthol, eucalyptus oil, aloe,
and similar substances are very effective as antipruritics. If the skin cracks deeply enough, a pathway for
infection is created. Topical antibiotics like bacitracin
are effective in prevention and in the early stages of
these skin infections. Cleansing with hydrogen peroxide inhibits infection as well.
Finally, there are topical and internal derivatives
of vitamin A called retinoids that improve skin growth
and are used for severe cases of acne, ichthyosis, and
other skin conditions. Tazarotene (Tazorac), a retinoid that was originally developed to treat psoriasis
and acne, appears to give good results in treating
ichthyosis with fewer side effects than other retinoids.

Prognosis
This condition requires continuous care throughout a lifetime. Properly treated, in most cases it is a
cosmetic problem. There are a small number of lethal
forms, such as harlequin fetus.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Ichthyosis.’’ Section 10, Chapter 121. In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PERIODICALS

Fleckman, P. ‘‘Management of the Ichthyoses.’’ Skin
Therapy Letter 8 (September 2003): 3–7.
Hatsell, S. J., H. Stevens, A. P. Jackson, et al. ‘‘An
Autosomal Recessive Exfoliative Ichthyosis with
Linkage to Chromosome 12q13.’’ British Journal of
Dermatology 149 (July 2003): 174–180.
Lefevre, C., S. Audebert, F. Jobard, et al. ‘‘Mutations in the
Transporter ABCA12 Are Associated with Lamellar
Ichthyosis Type 2.’’ Human Molecular Genetics 12
(September 15, 2003): 2369–2378.
Marulli, G. C., E. Campione, M. S. Chimenti, et al. ‘‘Type I
Lamellar Ichthyosis Improved by Tazarotene 0.1%
Gel.’’ Clinical and Experimental Dermatology 28 (July
2003): 391–393.
Okulicz, Jason F., MD, and Robert A. Schwartz, MD,
MPH. ‘‘Ichthyosis Vulgaris, Hereditary and Acquired.’’
eMedicine November 1, 2001. <http://
www.emedicine.com/derm/topic678.htm>.
1955

Ichthyosis

KEY TERMS

Idiopathic infiltrative lung diseases

ORGANIZATIONS

Alliance of Genetic Support Groups. 4301 Connecticut Ave.
NW, Suite 404, Washington, DC 20008. (202) 966-5557.
Fax: (202) 966-8553. <http://www.geneticalliance.org>.
Foundation for Ichthyosis and Related Skin Types (FIRST).
650 N. Cannon Ave., Suite 17, Landsdale, PA 19446.
(215) 631-1411 or (800) 545-3286. Fax: (215) 631-1413.
<http://www.scalyskin.org>.
National Organization for Rare Disorders, Inc. (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813.
(800) 999-6673 or (203) 744-0100. <http://
www.rarediseases.org>.

patients, no specific cause is ever found; they are said
to have idiopathic pulmonary fibrosis.
Some patients have special types of interstitial lung
disease that may occur in certain types of patients,
or feature typical pathological changes when a sample
of lung tissue is examined under a microscope. They
include:


Usual interstitial pneumonitis. Disease occurs in a
patchy form throughout the lungs. Parts of the lungs
can appear normal while others have dense scar tissue and lung cysts, often the end result of pulmonary
fibrosis. This disease progresses quite slowly. Both
children and adults may be affected.



Desquamative interstitial pneumonitis. Similarappearing lesions are present throughout the lungs.
Both inflammatory cells and cells that have separated from the air sac linings (‘‘desquamated’’) are
present. Some researchers believe this is an early
form of usual interstitial pneumonitis.



Lymphocytic interstitial pneumonitis. Most of the
cells infiltrating the lungs are the type of white
blood cells called lymphocytes. Both the breathing
tubes (bronchi) and blood vessels of the lungs
become thickened. In children, this condition tends
to occur when the immune system is not operating
properly as occurs with Acquired Immune Deficiency
Syndrome (AIDS).

OTHER

Immune Deficiency Foundation Website.
<www.primaryimmune.org>.

Catherine L. Tesla, MS, CGC
Rebecca J. Frey, PhD

Icterus see Jaundice
Idiopathic hypertrophic subaortic stenosis
see Hypertrophic cardiomyopathy

Idiopathic infiltrative lung
diseases
Definition
The term idiopathic means ‘‘cause unknown.’’ The
idiopathic infiltrative lung diseases, also known as
interstitial lung diseases, are a group of more than a
hundred disorders seen in both adults and (less often)
in children, whose cause is unknown but which tend to
spread, or ‘‘infiltrate’’ through much or all of the lung
tissue. They range from mild conditions that respond
well to treatment, to progressive, nonresponsive disease states that severely limit lung function and may
cause death.

Description
The body produces inflammatory cells in response
to a variety of conditions, including a number of different diseases, pollutants, certain infections, exposure
to organic dust or toxic fumes and vapors, and various
drugs and poisons. When white blood cells and tissue
fluid rich in protein collect in the small air sacs of the
lungs, or alveoli, the sacs become inflamed (alveolitis).
In time, the fluid may solidify and cause scar formation that replaces the normal lung tissue. This process
is known as pulmonary fibrosis. In about half of all
1956

Causes and symptoms
By definition, the causes of idiopathic infiltrative
lung diseases are not known. Some forms of pulmonary fibrosis, however, do have specific causes and these
may provide a clue as to what may cause idiopathic
diseases. Known causes of pulmonary fibrosis include
diseases that impair the body’s immune function;
infection by viruses and the bacterium causing tuberculosis; and exposure to such mineral dusts as silica or
asbestos, or such organic materials as bird droppings.
Other cases of pulmonary fibrosis result from exposure to fumes and vapors, radiation (in industry or
medically), and certain drugs used to treat disease.
Patients with interstitial lung disease usually have
labored breathing when exerting themselves. Often
they cough and feel overly tired (‘‘no stamina’’).
Wheezing is uncommon. When the physician listens
to the patient’s chest with a stethoscope, dry, crackling
sounds may be heard. Some patients have vague
chest pain. When disease progresses, the patient may
breathe very rapidly, have mottled blue skin (because
of getting too little oxygen), and lose weight. The
fingertips may appear thick or club-shaped.
GALE ENCYCLOPEDIA OF MEDICINE

Both scars in the lung and cysts (air-filled spaces)
can be seen on a chest x ray. Up to 10% of patients,
however, may have normal x rays even if their symptoms are severe. A special type of x ray, highresolution computed tomography scan (CT scan),
often is helpful in adult patients. Tests of lung function
will show that the lungs cannot hold enough air with
each breath, and there is too little oxygen in the blood,
especially after exercising. In a procedure called
bronchoalveolar lavage, a tube is placed through the
nose and windpipe into the bronchi and a small
amount of saline is released and then withdrawn.
This fluid can then be analyzed for cells. A tiny piece
of lung tissue can be sampled using the same instrument. If necessary, a larger sample (a biopsy) is taken
through an incision in the chest wall and examined
under a microscope.

Treatment
The first medication given, providing scarring is
not too extensive, is usually a steroid drug such as
prednisone. An occasional patient will improve dramatically if steroid therapy stops the inflammation.
Most patients, however, improve to a limited extent.
It may take 6–12 weeks for a patient to begin to
respond. Patients must be watched closely for a gain
in body weight, high blood pressure, and depression.
Steroids can also result in diabetes, ulcer disease, and
cataract. Patients treated with steroids are at risk of
contracting serious infection. If steroids have not
proved effective or have caused serious side effects,
other anti-inflammatory drugs, such as cyclophosphamide (Cytoxan) or azathioprine (Imuran), can be
tried. Cytoxan sometimes is combined with a steroid,
but it carries its own risks, which include bladder
inflammation and suppression of the bone marrow.
Some patients will benefit from a bronchodilator drug
that relaxes the airway and makes breathing easier.
Some patients with interstitial lung disease, especially children, will need oxygen therapy. Usually oxygen is given during sleep or exercise, but if the blood
oxygen level is very low it may be given constantly. A
program of conditioning, training in how to breathe
efficiently, energy-saving tips, and a proper diet will
help patients achieve the highest possible level of function given the state of their illness. All patients should
be vaccinated each year against influenza. A last resort
for those with very advanced disease who do not
respond to medication is lung transplantation. This
operation is being done more widely, and it is even
possible to replace both lungs.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Bronchoalveolar lavage—A way of obtaining a
sample of fluid from the airways by inserting a
flexible tube through the windpipe. Used to diagnose the type of lung disease.
Desquamation—Shedding of the cells lining the
insides of the air sacs. A feature of desquamative
interstitial pneumonitis.
Idiopathic—A disease whose cause is unknown.
Immune system—A set of body chemicals and specialized cells that attack an invading agent (such as
a virus) by forming antibodies that can engulf and
destroy it.
Infiltrative—A process whereby inflammatory or
other types of disease spread throughout an organ
such as the lungs.
Interstitial—Refers to the connective tissue that
supports the ‘‘working parts’’ of an organ, in the
case of the lungs the air sacs.
Pulmonary fibrosis—A scarring process that is
the end result of many forms of long-lasting lung
disease.

Prognosis
A scoring system based on lung function and x ray
appearances has been designed to help monitor a
patient’s course. In general, idiopathic forms of interstitial lung disease cause a good deal of illness, and a
significant number of deaths. A majority of patients
get worse over time, although survival for many years
is certainly possible. An estimated one in five affected
children fail to survive. In different series, survival
times average between four and ten years. Early diagnosis gives the best chance of a patient recovering or at
least stabilizing. Once the lungs are badly scarred,
nothing short of lung transplantation offers hope of
restoring lung function. Patients with desquamative
interstitial pneumonitis tend to respond well to steroid
treatment, and live longer than those with other types
of infiltrative lung disease.

Prevention
Since we do not understand what causes idiopathic interstitial lung diseases, there is no way to
prevent them. What can be done is to prevent
extensive scarring of the lungs by making the diagnosis shortly after the first symptoms develop,
and trying steroids or other drugs in hope of
1957

Idiopathic infiltrative lung diseases

Diagnosis

Idiopathic primary renal hematuric/proteinuric syndrome

suppressing lung inflammation. Every effort
should be made to avoid exposure to dusts,
gases, chemicals, and even pets. Keeping fit and
learning how to breathe efficiently will help maintain lung function as long as possible.

for this syndrome is suspected, this has not been proven. Symptoms often appear 24–48 hours after an
upper respiratory or gastrointestinal infection.
Symptoms of the syndrome include:


blood in the urine (hematuria)

Resources



protein in the urine (proteinuria)

ORGANIZATIONS



pain in the lower back or kidney area



elevated blood pressure (20–30% of cases)



nephrotic syndrome (less than 10% of cases)



swelling (occasionally)

American Lung Association. 1740 Broadway, New York, NY
10019. (800) 586-4872. <http://www.lungusa.org>.

David A. Cramer, MD

Idiopathic primary renal
hematuric/proteinuric
syndrome
Definition
This syndrome includes a group of disorders characterized by blood and protein in the urine and by
damage to the kidney glomeruli (filtering structures)
that may lead to kidney failure.

Description
This syndrome, also known as Berger’s disease or
IgA nephropathy, arises when internal kidney structures called glomeruli become inflamed and injured.
It can occur at any age, but the great majority of
patients are 16–35 when diagnosed. Males seem to
be affected more often than females, and whites are
more often affected than blacks. Blood in the urine
(hematuria), either indicated by a visible change in
the color of the urine or detected by laboratory testing, is a hallmark of this syndrome, and it may occur
continuously or sporadically. The pattern of occurrence is not indicative of the severity of kidney
damage.

Causes and symptoms
The glomeruli are the kidney structures that filter
the blood and extract waste, which is then excreted as
urine. The barrier between the blood and the urine side
of the filter mechanism is a membrane only one cell
layer thick. Anything that damages the membrane will
result in hematuria. Symptoms of idiopathic primary
renal hematruic/proteinuric syndrome are caused by
inflammation of the glomeruli and deposit of IgA
antibodies in kidney tissue. Although a genetic basis
1958

This condition usually does not get worse with
time, although renal failure occasionally results. In
patients with large amounts of IgA deposits in their
glomeruli, the long-term prognosis may not be favorable. The syndrome can go into remission spontaneously, although this is more common in children
than in adults.

Diagnosis
One of the objectives of diagnosis is to distinguish glomerular from non-glomerular kidney
diseases. Idiopathic primary hematuric/proteinuric
syndrome involves the glomeruli. The presence of
fragmented or distorted red blood cells in the urine
is evidence of glomerular disease. A high concentration of protein in the urine is also evidence for glomerular disease. The hematuria associated with this
syndrome must be distinguished from that caused by
urinary tract diseases, which can also cause a loss of
blood into the urine. Biopsy of the patient’s kidney
shows deposits of IgA antibodies. Detecting IgAantibody deposits rules out thin membrane disease
as the cause of the hematuria and proteinuria. Test
values are normal for ASO, complement, rheumatoid
factor, antinuclear antibodies, anti-DNase, and cryoglobulins, all of which are associated with different
types of kidney disease. A diagnosis of idiopathic
primary renal hematuric/proteinuric syndrome is largely made by ruling out other diseases and their
causes, leaving this syndrome as the remaining possible diagnosis.

Treatment
Many patients do not need specific treatment,
except for those who have symptoms indicating a
poor prognosis. Oral doses of corticosteroids are effective in patients with mild proteinuria and good kidney
function. Other treatments, such as medications
to lower blood pressure, are aimed at slowing or
GALE ENCYCLOPEDIA OF MEDICINE

Glomeruli (singular, glomerulus)—Filtering structures in the kidneys.
Hematuria—The presence of hemoglobin or red
blood cells in the urine.
Idiopathic—Refers to a disease that arises from an
obscure or unknown cause.
Nephrotic syndrome—A kidney disorder characterized by fluid retention (edema) and proteinuria.
It is caused by damage to the kidney glomeruli.
Proteinuria—The presence of protein in the urine
exceeding normal levels.

preventing kidney damage. If kidney failure develops,
dialysis or kidney transplantation is necessary.

Prognosis
Idiopathic primary renal hematuric/proteinuric
syndrome progresses slowly and in many cases does
not progress at all. Risk for progression of the disorder
is considered higher if there is:


high blood pressure



large amounts of protein in the urine



increased levels of urea and creatinine in the blood
(indications of kidney function)

About 25–35% of patients may develop kidney
failure within about 25 years.

Prevention
Since the underlying causes of this syndrome
are so poorly understood, there is no known
prevention.
Resources

Idiopathic thrombocytopenic
purpura
Definition
Idiopathic thrombocytopenic purpura, or ITP, is
a bleeding disorder caused by an abnormally low level
of platelets in the patient’s blood. Platelets are small
plate-shaped bodies in the blood that combine to form
a plug when a blood vessel is injured. The platelet plug
then binds certain proteins in the blood to form a clot
that stops bleeding. ITP’s name describes its cause and
two symptoms. Idiopathic means that the disorder has
no apparent cause. ITP is now often called immune
thrombocytopenic purpura rather than idiopathic
because of recent findings that ITP patients have autoimmune antibodies in their blood. Thrombocytopenia
is another word for a decreased number of blood
platelets. Purpura refers to a purplish or reddishbrown skin rash caused by the leakage of blood from
broken capillaries into the skin. Other names for
ITP include purpura hemorrhagica and essential
thrombocytopenia.

Description
ITP may be either acute or chronic. The acute
form is most common in children between the ages of
two and six years; the chronic form is most common in
adult females between 20 and 40. Between 10% and
20% of children with ITP have the chronic form. ITP
does not appear to be related to race, lifestyle, climate,
or environmental factors.
ITP is a disorder that affects the overall number
of blood platelets rather than their function. The
normal platelet level in adults is between 150,000
and 450,000/mm3. Platelet counts below 50,000 mm3
increase the risk of dangerous bleeding from trauma;
counts below 20,000/mm3 increase the risk of spontaneous bleeding.

Causes and Symptoms

BOOKS

Greenberg, A. Primer on Kidney Diseases. San Diego:
Academic Press, 1998.
ORGANIZATIONS

IgA Nephropathy Support Network. 964 Brown Ave.,
Huntington Valley, PA 19006. (215) 663–0536.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.

John T. Lohr, PhD
GALE ENCYCLOPEDIA OF MEDICINE

In adults, ITP is considered an autoimmune disorder, which means that the body produces antibodies
that damage some of its own products–in this case,
blood platelets. Some adults with chronic ITP also
have other immune system disorders, such as systemic
lupus erythematosus (SLE). In children, ITP is usually
triggered by a virus infection, most often rubella,
chickenpox, measles, cytomegalovirus, or EpsteinBarr virus. It usually begins about two or three
weeks after the infection.
1959

Idiopathic thrombocytopenic purpura

KEY TERMS

Idiopathic thrombocytopenic purpura

Acute ITP
Acute ITP is characterized by bleeding into the
skin or from the nose, mouth, digestive tract, or urinary tract. The onset is usually sudden. Bleeding into
the skin takes the form of purpura or petechiae.
Purpura is a purplish or reddish-brown rash or discoloration of the skin; petechiae are small round pinpoint hemorrhages. Both are caused by the leakage of
blood from tiny capillaries under the skin surface. In
addition to purpura and petechiae, the patient may
notice that he or she bruises more easily than usual. In
extreme cases, patients with ITP may bleed into the
lungs, brain, or other vital organs.
Chronic ITP
Chronic ITP has a gradual onset and may have
minimal or no external symptoms. The low platelet
count may be discovered in the course of a routine
blood test. Most patients with chronic ITP, however,
will consult their primary care doctor because of the
purpuric skin rash, nosebleeds, or bleeding from the
digestive or urinary tract. Women sometimes go to
their gynecologist for unusually heavy or lengthy menstrual periods.
The risk factors for the development of chronic
ITP include:


female sex



age over 10 years at onset of symptoms



slow onset of bruising



presence of other autoantibodies in the blood

Diagnosis
ITP is usually considered a diagnosis of exclusion,
which means that the doctor arrives at the diagnosis by a
process of ruling out other possible causes. If the patient
belongs to one or more of the risk groups for chronic
ITP, the doctor may order a blood test for autoantibodies in the blood early in the diagnostic process.
Physical examination
If the doctor suspects ITP, he or she will examine
the patient’s skin for bruises, purpuric areas, or petechiae. If the patient has had nosebleeds or bleeding
from the mouth or other parts of the body, the doctor
will examine these areas for other possible causes of
bleeding. Patients with ITP usually look and feel
healthy except for the bleeding.
The most important features that the doctor will
be looking for during the physical examination are the
1960

condition of the patient’s spleen and the presence of
fever. Patients with ITP do not have fever, whereas
patients with lupus and some other types of thrombocytopenia are usually feverish. The doctor will have
the patient lie flat on the examining table in order to
feel the size of the spleen. If the spleen is noticeably
enlarged, ITP is not absolutely ruled out but is a less
likely diagnosis.
Laboratory testing
The doctor will order a complete blood count
(CBC), a test of clotting time, a bone marrow test,
and a test for antiplatelet antibodies if it is available
in the hospital laboratory. Patients with ITP usually
have platelet counts below 20,000/mm3 and prolonged
bleeding time. The size and appearance of the platelets
may be abnormal. The red blood cell count (RBC) and
white blood cell count (WBC) are usually normal,
although about 10% of patients with ITP are also
anemic. The blood marrow test yields normal results.
Detection of antiplatelet antibodies in the blood is
considered to confirm the diagnosis of ITP.

Treatment
General care and monitoring
There is no specific treatment for ITP. In most
cases, the disorder will resolve without medications or
surgery within two to six weeks. Nosebleeds can be
treated with ice packs when necessary.
General care includes explaining ITP to the
patient and advising him or her to watch for bruising,
petechiae, or other signs of recurrence. Children
should be discouraged from rough contact sports or
other activities that increase the risk of trauma.
Patients are also advised to avoid using aspirin or
ibuprofen (Advil, Motrin) as pain relievers because
these drugs lengthen the clotting time of blood.
Emergency treatment
Patients with acute ITP who are losing large
amounts of blood or bleeding into their central nervous system require emergency treatment. This
includes transfusions of platelets, intravenous immunoglobulins, or prednisone. Prednisone is a steroid
medication that decreases the effects of antibody on
platelets and eventually lowers antibody production.
If the patient has a history of ITP that has not
responded to prednisone or immunoglobulins, the surgeon may remove the patient’s spleen. This operation
is called a splenectomy. The reason for removing the
spleen when ITP does not respond to other forms of
GALE ENCYCLOPEDIA OF MEDICINE

Autoimmune disorder—A disorder in which the
patient’s immune system produces antibodies that
destroy some of the body’s own products. ITP in
adults is thought to be an autoimmune disorder.
Idiopathic—Of unknown cause. Idiopathic refers
to a disease that is not preceded or caused by any
known dysfunction or disorder in the body.
Petechiae—Small pinpoint hemorrhages in skin or
mucous membranes caused by the rupture of
capillaries.
Platelet—A blood component that helps to prevent
blood from leaking from broken blood vessels. ITP
is a bleeding disorder caused by an abnormally low
level of platelets in the blood.
Prednisone—A corticosteroid medication that is
used to treat ITP. Prednisone works by decreasing
the effects of antibody on blood platelets. Longterm treatment with prednisone is thought to
decrease antibody production.
Purpura—A skin discoloration of purplish or
brownish red spots caused by bleeding from broken
capillaries.
Splenectomy—Surgical removal of the spleen.
Thrombocytopenia—An abnormal decline in the
number of platelets in the blood.

Splenectomy is usually avoided in children younger
than five years because of the increased risk of a severe
infection after the operation. In older children, however, splenectomy is recommended if the child has
been treated for 12 months without improvement; if
the ITP is very severe or the patient is getting worse; if
the patient begins to bleed into the head or brain; and
if the patient is an adolescent female with extremely
heavy periods.

Prognosis
The prognosis for recovery from acute ITP is
good; 80% of patients recover without special treatment. The prognosis for chronic ITP is also good;
most patients experience long-term remissions. In
rare instances, however, ITP can cause life-threatening
hemorrhage or bleeding into the central nervous
system.
Resources
BOOKS

Linker, Charles A. ‘‘Blood.’’ In Current Medical Diagnosis
and Treatment, 1998, edited by Stephen McPhee, et al.,
37th ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

IHSS see Hypertrophic cardiomyopathy
Ileal conduit see Urinary diversion surgery

treatment is that the spleen sometimes keeps platelets
out of the general blood circulation.

Ileocol see Crohn’s disease
Ileostomy see Enterostomy

Medications and transfusions
Patients with chronic ITP can be treated with
prednisone, immune globulin, or large doses of intravenous gamma globulin. Although 90% of patients
respond to immunoglobulin treatment, it is very
expensive. About 80% of patients respond to prednisone therapy. Platelet transfusions are not recommended for routine treatment of ITP. If the patient’s
platelet level does not improve within one to four
months, or requires high doses of prednisone, the
doctor may recommend splenectomy. All medications
for ITP are given either orally or intravenously; intramuscular injection is avoided because of the possibility
of causing bleeding into the skin.
Surgery
Between 80% and 85% of adults with ITP have a
remission of the disorder after the spleen is removed.
GALE ENCYCLOPEDIA OF MEDICINE

Ileus
Definition
Ileus is a partial or complete non-mechanical
blockage of the small and/or large intestine. The
term ‘‘ileus’’ comes from the Latin word for colic.

Description
There are two types of intestinal obstructions,
mechanical and non-mechanical. Mechanical obstructions occur because the bowel is physically blocked
and its contents can not pass the point of the obstruction. This happens when the bowel twists on itself
(volvulus) or as the result of hernias, impacted feces,
1961

Ileus

KEY TERMS

Ileus

abnormal tissue growth, or the presence of foreign
bodies in the intestines.
Unlike mechanical obstruction, non-mechanical
obstruction, called ileus or paralytic ileus, occurs
because peristalsis stops. Peristalsis is the rhythmic
contraction that moves material through the bowel.
Ileus is most often associated with an infection of the
peritoneum (the membrane lining the abdomen). It is
one of the major causes of bowel obstruction in infants
and children.
Another common cause of ileus is a disruption or
reduction of the blood supply to the abdomen. Handling
the bowel during abdominal surgery can also cause
peristalsis to stop, so people who have had abdominal
surgery are more likely to experience ileus. When ileus
results from abdominal surgery the condition is often
temporary and usually lasts only 48–72 hours.
Ileus sometimes occurs as a complication of
surgery on other parts of the body, including joint
replacement or chest surgery.
Ileus can also be caused by kidney diseases, especially when potassium levels are decreased. Heart
disease and certain chemotherapy drugs, such as vinblastine (Velban, Velsar) and vincristine (Oncovin,
Vincasar PES, Vincrex), also can cause ileus. Infants
with cystic fibrosis are more likely to experience meconium ileus (a dark green material in the intestine).
Over all, the total rate of bowel obstruction due both
to mechanical and non-mechanical causes is one in one
thousand people (1/1,000).

Causes and symptoms
When the bowel stops functioning, the following
symptoms occur:


abdominal cramping



abdominal distention



nausea and vomiting



failure to pass gas or stool

Diagnosis
When a doctor listens with a stethoscope to the
abdomen there will be few or no bowel sounds, indicating that the intestine has stopped functioning.
Ileus can be confirmed by x rays of the abdomen,
computed tomography scans (CT scans), or ultrasound. It may be necessary to do more invasive
tests, such as a barium enema or upper GI series, if
the obstruction is mechanical. Blood tests also are
useful in diagnosing paralytic ileus.
1962

Barium studies are used in cases of mechanical
obstruction, but may cause problems by increasing
pressure or intestinal contents if used in ileus. Also,
in cases of suspected mechanical obstruction involving the gastrointestinal tract (from the small intestine
downward) use of barium x rays are contraindicated,
since they may contribute to the obstruction. In such
cases a barium enema should always be done first.

Treatment
Patients may be treated with supervised bed rest in
a hospital and bowel rest. Bowel rest means that nothing is taken by mouth and patients are fed intravenously or through the use of a nasogastric tube. A
nasogastric tube is a tube inserted through the nose,
down the throat, and into the stomach. A similar tube
can be inserted in the intestine. The contents are then
suctioned out. In some cases, especially where there is
a mechanical obstruction, surgery may be necessary.
Drug therapies that promote intestinal motility
(ability of the intestine to move spontaneously), such
as cisapride and vasopressin (Pitressin), are sometimes
prescribed.

Alternative treatment
Alternative practitioners offer few treatment suggestions, but focus on prevention by keeping the
bowels healthy through eating a good diet, high in
fiber and low in fat. If the case is not a medical emergency, homeopathic treatment and traditional Chinese
medicine can recommend therapies that may help to
reinstate peristalsis.

Prognosis
The outcome of ileus varies depending on its
cause.

Prevention
Most cases of ileus are not preventable. Surgery to
remove a tumor or other mechanical obstruction will
help prevent a recurrence.
Some measures that have been recommended to
minimize the severity of postoperative ileus or shorten
its duration include making sure that any electrolyte
imbalances are corrected, and using nonopioid medications to relieve pain, as opioid drugs (including morphine, oxycodone, and codeine) tend to cause
constipation. One group of drugs that shows promise
for treating abdominal pain is a class of medications
known as kappa-opioid agonists. As of 2004, however,
GALE ENCYCLOPEDIA OF MEDICINE

Computed tomography scan (or CT scan)—A computer enhanced x-ray study performed to detect
abnormalities that do not show up on normal x rays.
Meconium—A greenish fecal material that forms
the first bowel movement of an infant.
Peritoneum—The transparent membrane lining the
abdominal cavity that holds internal organs in place.

these drugs are still under investigation for controlling
visceral pain in humans.

This is done to prevent an injured area from moving
while it heals.

Purpose
Splints, casts, and braces support and protect
broken bones, dislocated joints, and such injured soft
tissue as tendons and ligaments. Immobilization
restricts motion to allow the injured area to heal. It
can help reduce pain, swelling, and muscle spasm. In
some cases, splints and casts are applied after surgical
procedures that repair bones, tendons, or ligaments.
This allows for protection and proper alignment early
in the healing phase.

Precautions

Resources
BOOKS

There are no special precautions for immobilization.

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Ileus.’’ Section 3, Chapter 25. In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.

Description

PERIODICALS

Baig, M. K., and and S. D. Wexner. ‘‘Postoperative Ileus:
A Review.’’ Diseases of the Colon and Rectum 47
(April 2004): 516–526.
Lassandro, F., N. Gagliardi, M. Scuderi, et al. ‘‘Gallstone
Ileus Analysis of Radiological Findings in 27 Patients.’’
European Journal of Radiology 50 (April 2004): 23–29.
Pavone, P., T. Johnson, P. S. Saulog, et al. ‘‘Perioperative
Morbidity in Bilateral One-Stage Total Knee
Replacements.’’ Clinical Orthopaedics and Related
Research 421 (April 2004): 155–161.
Riviere, P. J. ‘‘Peripheral Kappa-Opioid Agonists for
Visceral Pain.’’ British Journal of Pharmacology 141
(April 2004): 1331–1334.
OTHER

‘‘Bowel Paralysis.’’ Trigan Oncology Associates Page.
<http://www.trigan.com/ileus.htm>.
‘‘Intestinal Obstruction.’’ HealthAnswers.com. <http://
www.healthanswers.com/database/ami/converted/
000260.html>.

Tish Davidson, A. M.
Rebecca J. Frey, PhD

Immobilization
Definition
Immobilization refers to the process of holding a
joint or bone in place with a splint, cast, or brace.
GALE ENCYCLOPEDIA OF MEDICINE

When an arm, hand, leg, or foot requires immobilization, the cast, splint, or brace will generally
extend from the joint above the injury to the joint
below the injury. For example, an injury to the midcalf requires immobilization from the knee to the
ankle and foot. Injuries of the hip and upper thigh or
shoulder and upper arm require a cast that encircles
the body and extends down the injured leg or arm.
Casts and splints
Casts are generally used for immobilization of a
broken bone. Once the doctor makes sure the two broken ends of the bone are aligned, a cast is put on to keep
them in place until they are rejoined through natural
healing. Casts are applied by a physician, a nurse, or an
assistant. They are custom-made to fit each person, and
are usually made of plaster or fiberglass. Fiberglass
weighs less than plaster, is more durable, and allows
the skin more adequate airflow than plaster. A layer of
cotton or synthetic padding is first wrapped around the
skin to cover the injured area and protect the skin. The
plaster or fiberglass is then applied over this.
Most casts should not be gotten wet. However,
some types of fiberglass casts use Gore-tex padding
that is waterproof and allows the person to completely
immerse the cast in water when taking a shower or
bath. There are some circumstances when this type of
cast material can not be used.
A splint is often used to immobilize a dislocated
joint while it heals. Splints are also often used for
finger injuries, such as fractures or baseball finger.
Baseball finger is an injury in which the tendon at the
1963

Immobilization

KEY TERMS

Immobilization

Air splint

Triangle sling

Cravat sling

Basket sling
Board splint

Immobilization refers to the process of immobilizing or fixating the position of a joint, bone, extremity, or torso with a splint,
cast, or brace. Immobilization can help reduce pain, swelling, and muscle spasms. The illustrations above feature several types
of immobilization techniques. (Illustration by Electronic Illustrators Group.)

end of the finger is separated from the bone as a result
of trauma. Splinting also is used to immobilize an
injured arm or leg immediately after an injury.
Before moving a person who has injured an arm or
leg some type of temporary splint should be applied to
prevent further injury to the area. Splints may be made
of acrylic, polyethylene foam, plaster of paris, or aluminum. In an emergency, a splint can be made from a
piece of wood or rolled magazine.
Slings
Slings are often used to support the arm after a
fracture or other injury. They are generally used along
with a cast or splint, but sometimes are used alone as a
means of immobilization. They can be used in an
emergency to immobilize the arm until the person
can be seen by a doctor. A triangular bandage is placed
under the injured arm and then tied around the neck.
Braces
Braces are used to support, align, or hold a body
part in the correct position. Braces are sometimes used
after a surgical procedure is performed on an arm or
leg. They can also be used for an injury. Since some
braces can be easily taken off and put back on, they are
often used when the person must have physical therapy or exercise the limb during the healing process.
Many braces can also be adjusted to allow for a certain
amount of movement.
Braces can be custom-made, or a ready-made
brace can be used. The off-the-shelf braces are made
in a variety of shapes and sizes. They generally have
1964

Velcro straps that make the brace easy to adjust, and
to put on and take off. Both braces and splints offer
less support and protection than a cast and may not be
a treatment option in all circumstances.
Collars
A collar is generally used for neck injuries. A soft
collar can relieve pain by restricting movement of the
head and neck. They also transfer some of the weight of
the head from the neck to the chest. Stiff collars are
generally used to support the neck when there has been
a fracture in one of the bones of the neck. Cervical collars
are widely used by emergency personnel at the scene of
injuries when there is a potential neck or head injury.
Traction
Immobilization may also be secured by traction.
Traction involves using a method for applying tension
to correct the alignment of two structures (such as two
bones) and hold them in the correct position. For example, if the bone in the thigh breaks, the broken ends may
have a tendency to overlap. Use of traction will hold
them in the correct position for healing to occur. The
strongest form of traction involves inserting a stainless
steel pin through a bony prominence attached by a
horseshoe-shaped bow and rope to a pulley and weights
suspended over the end of the patient’s bed.
Traction must be balanced by countertraction.
This is obtained by tilting the bed and allowing the
patient’s body to act as a counterweight. Another
technique involves applying weights pulling in the
opposite direction.
GALE ENCYCLOPEDIA OF MEDICINE

All traction requires careful observation and
adjustment by doctors and nurses to maintain proper
balance and alignment of the traction with free suspension of the weights.
Immobilization can also be secured by a form of
traction called skin traction. This is a combination of a
splint and traction that is applied to the arms or legs by
strips of adhesive tape placed over the skin of the arm or
leg. Adhesive strips, moleskin, or foam rubber traction
strips are applied on the skin. This method is effective
only if a moderate amount of traction is required.

Preparation
There are many reasons for immobilization using
splints, casts, and braces. Each person should understand his or her diagnosis clearly.

Aftercare
After a cast or splint has been put on, the injured
arm or leg should be elevated for 24 to 72 hours. It is
recommended that the person lie or sit with the injured
arm or leg raised above the level of the heart. Rest
combined with elevation will reduce pain and speed
the healing process by minimizing swelling.
Fingers or toes can be exercised as much as can be
tolerated after casting. This has been found to
decrease swelling and prevent stiffness. If excessive
swelling is noted, the application of ice to the splint
or cast may be helpful.
After the cast, splint, or brace is removed, gradual
exercise is usually performed to regain muscle strength
and motion. The doctor may also recommend hydrotherapy, heat treatments, and other forms of physical therapy.

Risks
For some people, such as those in traction, immobilization will require long periods of bedrest. Lying in
one position in bed for an extended period of time can
result in sores on the skin (decubitus ulcers) and skin
infection. Long periods of bedrest can also cause a
buildup of fluid in the lungs or an infection in the
lungs (pneumonia). Urinary infection can also be a
result of extended bedrest.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Decubitus ulcers — A pressure sore resulting from
ulceration of the skin occurring in persons confined
to bed for long periods of time
Ligament—Ligaments are structures that hold
bones together and prevent excessive movement
of the joint. They are tough, fibrous bands of tissue.
Pneumonia — An acute or chronic disease characterized by inflammation of the lungs and caused by
viruses, bacteria, or other microorganisms.
Tendon—Tendons are structures that attach bones
to muscles and muscles to other muscles.

People who have casts, splints, or braces on their
arms or legs will generally spend several weeks not
using the injured arm or leg. This lack of use can result
in decreased muscle tone and shrinkage of the muscle
(atrophy). Much of this loss can usually be regained,
however, through rehabilitation after the injury has
healed.
Immobility can also cause psychological stress.
An individual restricted to a bed with a traction device
may become frustrated and bored, and perhaps even
depressed, irritable, and withdrawn.
There is the possibility of decreased circulation if the
cast, splint, or brace fits too tightly. Excessive pressure
over a nerve can cause irritation or possible damage if
not corrected. If the cast, splint, or brace breaks or
malfunctions, the healing process of the bone or soft
tissue can be disrupted and lead to deformity.

Normal results
Normally, the surgical or injured area heals
appropriately with the help of immobilization. The
form of immobilization can be discontinued, which is
followed by an appropriate rehabilitation program
under the supervision of a physical therapist to regain
range of motion and strength.
Resources
OTHER

‘‘Casts & Splints.’’ The Center for Orthopaedics and Sports
Medicine. <http://www.arthroscopy.com>.

Jeffrey P. Larson, RPT

Immune complex detection see Immune
complex test
1965

Immobilization

Traction for neck injuries may be in the form of a
leather or cotton cloth halter placed around the chin
and lower back of the head. For very severe neck
injuries that require maximum traction, tongs that
resemble ice tongs are inserted into small holes drilled
in the outer skull.

Immune complex test

KEY TERMS

Immune complex test
Definition
These tests evaluate the immune system, whose
function is to defend the body against such invaders
as bacteria and viruses. The immune system also plays
a role in the control of cancer, and is responsible for
the phenomena of allergy, hypersensitivity, and rejection problems when organs or tissue are transplanted.
One of the ways the immune system protects the
body is by producing proteins called antibodies.
Antibodies are formed in response to another type of
protein called an antigen (anything foreign or different
from a natural body protein). Immune complex reactions occur when large numbers of antigen-antibody
complexes accumulate in the body.

Purpose
The purpose of the immune complex test is to
demonstrate circulating immune complexes in the
blood, to estimate the severity of immune complex
disease, and to monitor response to therapy.

Antibody—A (immunoglobulin) molecule that interacts with a specific antigen. Antibodies provide
protection from microscopic invaders like bacteria.
Antigen—Any substance that is capable under certain circumstances of producing an immune
response either from antibodies or T-cells; bacteria
are often antigens.
Autoimmune disorder—A disorder caused by a
reaction of an individual’s immune system against
the organs or tissues of the body. Autoimmune processes can have different results: slow destruction of
a particular type of cell or tissue, stimulation of an
organ into excessive growth, or interference in
function.
Biopsy—The removal and examination, usually
under a microscope, of tissue from the living body.
Used for diagnosis.
Systemic lupus erythematosus—A chronic disease
of the connective tissues in the body; characterized
by involvement of the skin, joints, kidneys, and
serosal membranes (membranes that form the
outer covering of organs in the abdomen or chest).

Precautions
Because this test is requested when the physician
suspects that a patient’s immune system is not functioning properly, special care should be taken during
and after blood is drawn. For example, the venipuncture site should be kept clean and dry to avoid any
chance of infection.

Description
Immune complexes are normally not detected in
the blood. However, when immune complexes are
produced faster than they can be cleared by the system, immune complex disease may occur. Examples of
such disorders are drug sensitivity, rheumatoid arthritis, and a disease called systemic lupus erythematosus,
or SLE.
The method generally used for detecting immune
complexes is examination of a tissue obtained by
biopsy (removal and examination of tissue sample)
and the subsequent use of different staining techniques
with specific antibodies. However, since tissue biopsies
do not provide information about the level of complexes still in the circulatory system, serum assays
obtained from blood samples which indirectly detect
circulating immune complexes are useful. However,
due to the variability of these complexes, several test
1966

methods may be used. Also, as most immune complex
assays have not been standardized, more than one test
may be required to achieve accurate results.

Preparation
This test requires a blood sample. It is not necessary for the patient to be in a fasting (nothing to eat or
drink) state before the test.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or
feeling lightheaded after venipuncture, or hematoma
(blood accumulating under the puncture site).

Normal results
Normally, immune complexes are not detected in
the blood.

Abnormal results
The presence of detectable immune complexes in
the blood is important in the diagnosis of autoimmune
GALE ENCYCLOPEDIA OF MEDICINE

divided into two components: humoral immunity and
cellular immunity.

Resources

The adaptive component of the immune system is
extremely complex, and is still not entirely understood. Basically, it has the ability to recognize an
organism or tumor cell as not being a normal part of
the body, and to develop a response to attempt to
eliminate it.

BOOKS

Jacobs, David S., et al. Laboratory Test Handbook. 4th ed.
New York: Lexi-Comp Inc., 1996.

Janis O. Flores

Immunodeficiency
Definition
Immunodeficiency disorders are a group of disorders in which part of the immune system is missing
or defective. Therefore, the body’s ability to fight
infections is impaired. As a result, the person with an
immunodeficiency disorder will have frequent infections that are generally more severe and last longer
than usual.

Description
The immune system is the body’s main method for
fighting infections. Any defect in the immune system
decreases a person’s ability to fight infections. A person with an immunodeficiency disorder may get more
frequent infections, heal more slowly, and have a
higher incidence of some cancers.
The normal immune system involves a complex
interaction of certain types of cells that can recognize
and attack ‘‘foreign’’ invaders, such as bacteria,
viruses, and fungi. It also plays a role in fighting
cancer. The immune system has both innate and adaptive components. Innate immunity is made up of
immune protections people are born with. Adaptive
immunity develops throughout life. It adapts to fight
off specific invading organisms. Adaptive immunity is
GALE ENCYCLOPEDIA OF MEDICINE

The innate immune system is made up of the skin
(which acts as a barrier to prevent organisms from
entering the body), white blood cells called phagocytes, a system of proteins called the complement
system, and chemicals called interferons. When phagocytes encounter an invading organism, they surround and engulf it to destroy it. The complement
system also attacks bacteria. The elements in the
complement system create a hole in the outer layer of
the target cell, which leads to the death of the cell.

The humoral response of adaptive immunity
involves a type of cell called B lymphocytes. B lymphocytes manufacture proteins called antibodies
(which are also called immunoglobulins). Antibodies
attach themselves to the invading foreign substance.
This allows the phagocytes to begin engulfing and
destroying the organism. The action of antibodies
also activates the complement system. The humoral
response is particularly useful for attacking bacteria.
The cellular response of adaptive immunity is useful for attacking viruses, some parasites, and possibly
cancer cells. The main type of cell in the cellular
response is T lymphocytes. There are helper T lymphocytes and killer T lymphocytes. The helper
T lymphocytes play a role in recognizing invading
organisms, and they also help killer T lymphocytes to
multiply. As the name suggests, killer T lymphocytes
act to destroy the target organism.
Defects can occur in any component of the
immune system or in more than one component (combined immunodeficiency). Different immunodeficiency diseases involve different components of the
immune system. The defects can be inherited and/or
present at birth (congenital) or acquired.
Congenital immunodeficiency disorders
Congenital immunodeficiency is present at the time
of birth, and is the result of genetic defects. These
immunodeficiency disorders are also called primary
immunodeficiencies. Even though more than 70 different types of congenital immunodeficiency disorders
have been identified, they rarely occur. About 50,000
new cases are diagnosed in the United States each year.
Congenital immunodeficiencies may occur as a result of
1967

Immunodeficiency

diseases, such as SLE and rheumatoid arthritis.
However, for definitive diagnosis, the results of other
studies must be considered with the presence of any
immune complex. For example, immune complexes
are associated with high numbers of a component
called antinuclear antibodies in the diagnosis of systemic lupus erythematosus. A different example are
the kidneys. Because of their filtering functions, elements in the kidneys called renal glomeruli can be
affected by immune complexes. In such cases, renal
biopsy is used to provide conclusive evidence for
immune complex.

Immunodeficiency

defects in B lymphocytes, T lymphocytes, or both. They
also can occur in the innate immune system.
HUMORAL IMMUNITY DISORDERS. Bruton’s agammaglobulinemia, also known as X-linked agammaglobulinemia, a congenital immunodeficiency disorder.
The defect results in a decrease or absence of B lymphocytes, and therefore a decreased ability to make
antibodies. People with this disorder are particularly
susceptible to infections of the throat, skin, middle ear,
and lungs. It is seen only in males because it is caused
by a genetic defect on the X chromosome. Since males
have only one X chromosome, they always have the
defect if the gene is present. Females can have
the defective gene, but since they have two X chromosomes, there will be a normal gene on the other X
chromosome to counter it. Women may pass the
defective gene on to their male children.
B LYMPHOCYTE DEFICIENCIES. If there is an
abnormality in either the development or function of
B lymphocytes, the ability to make antibodies will be
impaired. This allows the body to be susceptible to
recurrent infections.

A type of B lymphocyte deficiency involves a
group of disorders called selective immunoglobulin
deficiency syndomes. Immunoglobulin is another
name for antibody, and there are five different types
of immunoglobulins (called IgA, IgG, IgM, IgD, and
IgE). The most common type of immunoglobulin deficiency is selective IgA deficiency, occurring in about
one in every 500 white persons. The amounts of the
other antibody types are normal. Some patients with
selective IgA deficiency experience no symptoms,
while others have occasional lung infections and diarrhea. In another immunoglobulin disorder, IgG and
IgA antibodies are deficient and there is increased
IgM. People with this disorder tend to get severe bacterial infections.
Common variable immunodeficiency is another
type of B lymphocyte deficiency. In this disorder, the
production of one or more of the immunoglobulin
types is decreased and the antibody response to infections is impaired. It generally develops around the age
of 10-20. The symptoms vary among affected people.
Most people with this disorder have frequent infections, and some also will experience anemia and rheumatoid arthritis. Many people with common variable
immunodeficiency develop cancer.
T LYMPHOCYTE DEFICIENCIES. Severe defects in the

ability of T lymphocytes to mature results in impaired
immune responses to infections with viruses, fungi,
and certain types of bacteria. These infections are
usually severe and can be fatal.
1968

DiGeorge syndrome is a T lymphocyte deficiency
that starts during fetal development and is the result
of a deletion in a particular chromosome. Children
with DiGeorge syndrome either do not have a thymus
or have an underdeveloped thymus. Since the thymus
is a major organ that directs the production of
T-lymphocytes, these patients have very low numbers
of T-lymphocytes. They are susceptible to recurrent
infections, and usually have physical abnormalities
as well. For example, they may have low-set ears, a
small receding jawbone, and wide-spaced eyes.
People with DiGeorge syndrome are particularly susceptible to viral and fungal infections.
In some cases, no treatment is required for
DiGeorge syndrome because T lymphocyte production improves. Either an underdeveloped thymus
begins to produce more T lymphocytes or organ sites
other than the thymus compensate by producing more
T lymphocytes.
COMBINED IMMUNODEFICIENCIES. Some types of
immunodeficiency disorders affect both B lymphocytes and T lymphocytes. For example, severe combined immunodeficiency disease (SCID) is caused by
the defective development or function of these two
types of lymphocytes. It results in impaired humoral
and cellular immune responses. SCID usually is recognized during the first year of life. It tends to cause a
fungal infection of the mouth (thrush), diarrhea, failure to thrive, and serious infections. If not treated with
a bone marrow transplant, a person with SCID will
generally die from infections before age two. In 2003, a
report showed a new form of severe SCID with severe
mutation of T receptor cells.
DISORDERS OF INNATE IMMUNITY. Disorders of
innate immunity affect phagocytes or the complement
system. These disorders also result in recurrent
infections.

Acquired immunodeficiency disorders
Acquired immunodeficiency is more common
than congenital immunodeficiency. It is the result of
an infectious process or other disease. For example,
the human immunodeficiency virus (HIV) is the virus
that causes acquired immunodeficiency syndrome
(AIDS). However, this is not the most common cause
of acquired immunodeficiency.
Acquired immunodeficiency often occurs as a
complication of other conditions and diseases. For
example, the most common causes of acquired immunodeficiency are malnutrition, some types of cancer,
and infections. People who weigh less than 70% of the
average weight of persons of the same age and gender
GALE ENCYCLOPEDIA OF MEDICINE

In 2003, a new infection emerged that produces
immunodeficiency. Severe acute respiratory syndrome
(SARS) mysteriously appeared in a hospital in China.
It eventually affected 8,000 people in Asia and
Canada, killing 800 altogether. The virus is characterized by fever, lower respiratory tract symptoms, and
abnormal chest x rays. However, it also produces
immunodeficiency. No cases of the disease were
reported from July 2003 through December 2003,
but scientists feared it would reappear.
Sometimes, acquired immunodeficiency is
brought on by drugs used to treat another condition.
For example, patients who have an organ transplant
are given drugs to suppress the immune system so the
body will not reject the organ. Also, some chemotherapy drugs, which are given to treat cancer, have the
side effect of killing cells of the immune system.
During the period of time that these drugs are being
taken, the risk of infection increases. It usually
returns to normal after the person stops taking
the drugs.

Causes and symptoms
Congenital immunodeficiency is caused by genetic
defects, which generally occur while the fetus is developing in the womb. These defects affect the development and/or function of one or more of the
components of the immune system. Acquired immunodeficiency is the result of a disease process, and it
occurs later in life. The causes, as described above, can
be diseases, infections, or the side effects of drugs given
to treat other conditions.
People with an immunodeficiency disorder tend to
become infected by organisms that do not usually
cause disease in healthy persons. The major symptoms
of most immunodeficiency disorders are repeated
infections that heal slowly. These chronic infections
cause symptoms that persist for long periods of time.
People with chronic infection tend to be pale and thin.
They may have skin rashes. Their lymph nodes tend to
be larger than normal and their liver and spleen also
may be enlarged. The lymph nodes are small organs
that house antibodies and lymphocytes. Broken blood
vessels, especially near the surface of the skin, may be
seen. This can result in black-and-blue marks in the
skin. The person may lose hair from their head.
GALE ENCYCLOPEDIA OF MEDICINE

Sometimes, a red inflammation of the lining of the
eye (conjunctivitis) is present. They may have a crusty
appearance in and on the nose from chronic nasal
dripping.

Diagnosis
Usually, the first sign that a person might have an
immunodeficiency disorder is that they do not improve
rapidly when given antibiotics to treat an infection.
Strong indicators that an immunodeficiency disorder
may be present is when rare diseases occur or the
patient gets ill from organisms that do not normally
cause diseases, especially if the patient gets repeatedly
infected. If this happens in very young children it is
an indication that a genetic defect may be causing
an immunodeficiency disorder. When this situation
occurs in older children or young adults, their medical
history will be reviewed to determine if childhood
diseases may have caused an immunodeficiency disorder. Other possibilities will then be considered, such
as recently acquired infections–for example, HIV,
hepatitis, tuberculosis, etc.
Laboratory tests are used to determine the exact
nature of the immunodeficiency. Most tests are performed on blood samples. Blood contains antibodies,
lymphocytes, phagocytes, and complement components—all of the major immune components that
might cause immunodeficiency. A blood cell count
will determine if the number of phagocytic cells or
lymphocytes is below normal. Lower than normal
counts of either of these two cell types correlates with
immunodeficiencies. The blood cells also are checked
for their appearance. Sometimes a person may have
normal cell counts, but the cells are structurally defective. If the lymphocyte cell count is low, further testing
is usually done to determine whether any particular
type of lymphocyte is lower than normal. A lymphocyte proliferation test is done to determine if the lymphocytes can respond to stimuli. The failure to
respond to stimulants correlates with immunodeficiency. Antibody levels can be measured by a process
called electrophoresis. Complement levels can be
determined by immunodiagnostic tests.

Treatment
There is no cure for immunodeficiency disorders.
Therapy is aimed at controlling infections and, for
some disorders, replacing defective or absent
components.
Patients with Bruton’s agammaglobulinemia
must be given periodic injections of a substance called
1969

Immunodeficiency

are considered to be malnourished. Examples of
types of infections that can lead to immunodeficiency are chickenpox, cytomegalovirus, German measles,
measles, tuberculosis, infectious mononucleosis (EpsteinBarr virus), chronic hepatitis, lupus, and bacterial and
fungal infections.

Immunodeficiency

gamma globulin throughout their lives to make up for
their decreased ability to make antibodies. The gamma
globulin preparation contains antibodies against common invading bacteria. If left untreated, the disease
usually is fatal.

patient. Among the essential nutrients required by the
immune system are proteins, vitamins, iron, and zinc.

Common variable immunodeficiency also is
treated with periodic injections of gamma globulin
throughout life. Additionally, antibiotics are given
when necessary to treat infections.

In general, people with immunodeficiency disorders should maintain a healthy diet. This is because
malnutrition can aggravate immunodeficiencies. They
also should avoid being near people who have colds or
are sick because they can easily acquire new infections.
For the same reason, they should practice good personal hygiene, especially dental care. People with immunodeficiency disorders also should avoid eating
undercooked food because it might contain bacteria
that could cause infection. This food would not cause
infection in normal persons, but in someone with an
immunodeficiency, food is a potential source of infectious organisms. People with immunodeficiency
should be given antibiotics at the first indication of
an infection.

Patients with selective IgA deficiency usually do
not require any treatment. Antibiotics can be given for
frequent infections.
In some cases, no treatment is required for
DiGeorge syndrome because T lymphocyte production improves on its own. Either an underdeveloped
thymus begins to produce more T lymphocytes or
organ sites other than the thymus compensate by producing more T lymphocytes. In some severe cases, a
bone marrow transplant or thymus transplant can be
done to correct the problem.
For patients with SCID, bone marrow transplantation is necessary. In this procedure, healthy bone marrow from a donor who has a similar type of tissue
(usually a relative, like a brother or sister) is removed.
The bone marrow is a substance that resides in the
cavity of bones. It is the factory that produces blood,
including some of the white blood cells that make up
the immune system. The bone marrow of the person
receiving the transplant is destroyed, and is then
replaced with marrow from the donor.
Treatment of the HIV infection that causes AIDS
consists of drugs called antiretrovirals. These drugs
attempt to inhibit the process that the virus goes
through to kill T lymphocytes. Several of these drugs
used in various combinations with one another can
prolong the period of time before the disease becomes
apparent. However, this is not a cure. Other treatments for people with AIDS are aimed at the particular infections and conditions that arise as a result of
the impaired immune system. SARS is a relatively new
acquired disease. Treatment to date involves combination therapy with steroids and interferon and supplemental oxygen for breathing difficulties. In 2004,
reports in the United States said that a drug called
octagam 5%, an intravenous immunoglobulin, was
used to treat primary immunodeficiency diseases.
The drug has been used in Europe for the same
purpose.
In most cases, immunodeficiency caused by malnutrition is reversible. The health of the immune system is directly linked to the nutritional status of the
1970

For people being treated for cancer, periodic relief
from chemotherapy drugs can restore the function of
the immune system.

Prognosis
The prognosis depends on the type of immunodeficiency disorder. People with Bruton’s agammaglobulinemia who are given injections of gamma globulin
generally live into their 30s or 40s. They often die from
chronic infections, usually of the lung. People with
selective IgA deficiency generally live normal lives.
They may experience problems if given a blood transfusion, and therefore they should wear a Medic Alert
bracelet or have some other way of alerting any physician who treats them that they have this disorder.
SCID is the most serious of the immunodeficiency
disorders. If a bone marrow transplant is not successfully performed, the child usually will not live beyond
two years old.
People with HIV/AIDS are living longer than in
the past because of the antiretroviral drugs that became
available in the mid 1990s. However, AIDS still is a
fatal disease. People with AIDS usually die of opportunistic infections, which are infections that occur
because the impaired immune system is unable to
fight them.

Prevention
There is no way to prevent a congenital immunodeficiency disorder. However, someone with a congenital immunodeficiency disorder might want to
consider getting genetic counseling before having children to find out if there is a chance they will pass the
defect on to their children.
GALE ENCYCLOPEDIA OF MEDICINE

Agammaglobulinemia—The lack of gamma globulins in the blood. Antibodies are the main gamma
globulins of interest, so this term means a lack of
antibodies.

Some of the infections associated with acquired
immunodeficiency can be prevented or treated before
they cause problems. For example, there are effective
treatments for tuberculosis and most bacterial and
fungal infections. HIV infection can be prevented by
practicing ‘‘safe sex’’ and not using illegal intravenous
drugs. These are the primary routes of transmitting the
virus. For people who do not know the HIV status of
the person with whom they are having sex, safe sex
involves using a condom.
Malnutrition can be prevented by getting adequate nutrition. Malnutrition tends to be more of a
problem in developing countries.
Resources
PERIODICALS

‘‘2003 Begins With SARS, Ends With Flu.’’ Medical Letter
on the CDC & FDA January 11, 2004: 24.
Cooper, Megan A., Thomas L. Pommering, and Katalin
Koranyi. ‘‘Primary Immunodeficiencies.’’ American
Family Physician November 15, 2003: 2001.
Fischer, Alain. ‘‘Have We Seen the Last Variant of Severe
Combined Immunodeficiency?’’ The New England
Journal of Medicine November 6, 2003: 1789.
Low, Donald E., and Allison McGreer. ‘‘SARS— One Year
Later.’’ The New England Journal of Medicine
December 18, 2003: 2381.
‘‘Octagam is Efficacious for Treating Primary Immuno
deficiency Diseases.’’ Medical Letter on the CDC &
FDA July 11, 2004: 52.
‘‘Preliminary Report Suggests Combination Therapy May
Help Treat SARS.’’ Drug Week January 9, 2004: 557.

John T. Lohr, PhD
Teresa G. Odle

Immunoelectrophoresis
Definition
Immunoelectrophoresis, also called gamma globulin electrophoresis, or immunoglobulin electrophoresis,
GALE ENCYCLOPEDIA OF MEDICINE

is a method of determining the blood levels of
three major immunoglobulins: immunoglobulin
M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA).

Purpose
Immunoelectrophoresis is a powerful analytical
technique with high resolving power as it combines
separation of antigens by electrophoresis with immunodiffusion against an antiserum. The increased resolution is of benefit in the immunological examination
of serum proteins. Immunoelectrophoresis aids in the
diagnosis and evaluation of the therapeutic response
in many disease states affecting the immune system.
It is usually requested when a different type of electrophoresis, called a serum protein electrophoresis,
has indicated a rise at the immunoglobulin level.
Immunoelectrophoresis is also used frequently to
diagnose multiple myeloma, a disease affecting the
bone marrow.

Precautions
Drugs that may cause increased immunoglobulin
levels include therapeutic gamma globulin, hydralazine,
isoniazid, phenytoin (Dilantin), procainamide, oral
contraceptives, methadone, steroids, and tetanus toxoid
and antitoxin. The laboratory should be notified if the
patient has received any vaccinations or immunizations
in the six months before the test. This is mainly because
prior immunizations lead to the increased immunoglobulin levels resulting in false positive results.
It should be noted that, because immunoelectrophoresis is not quantitative, it is being replaced by a
procedure called immunofixation, which is more sensitive and easier to interpret.

Description
Serum proteins separate in agar gels under the influence of an electric field into albumin, alpha 1, alpha 2,
and beta and gamma globulins. Immunoelectrophoresis
is performed by placing serum on a slide containing a gel
designed specifically for the test. An electric current is
then passed through the gel, and immunoglobulins,
which contain an electric charge, migrate through the
gel according to the difference in their individual electric
charges. Antiserum is placed alongside the slide to identify the specific type of immunoglobulin present. The
results are used to identify different disease entities, and
to aid in monitoring the course of the disease and the
therapeutic response of the patient to such conditions as
immune deficiencies, autoimmune disease, chronic
1971

Immunoelectrophoresis

KEY TERMS

Immunoelectrophoresis

infections, chronic viral infections, and intrauterine fetal
infections.
There are five classes of antibodies: IgM, IgG,
IgA, IgE, and IgD.
IgM is produced upon initial exposure to an antigen. For example, when a person receives the first
tetanus vaccination, antitetanus antibodies of the
IgM class are produced 10 to 14 days later. IgM is
abundant in the blood but is not normally present in
organs or tissues. IgM is primarily responsible for
ABO blood grouping and rheumatoid factor, yet is
involved in the immunologic reaction to other infections, such as hepatitis. Since IgM does not cross the
placenta, an elevation of this immunoglobulin in the
newborn indicates intrauterine infection such as
rubella, cytomegalovirus (CMV) or a sexually transmitted disease (STD).
IgG is the most prevalent type of antibody, comprising approximately 75% of the serum immunoglobulins. IgG is produced upon subsequent exposure to
an antigen. As an example, after receiving a second
tetanus shot, or booster, a person produces IgG antibodies in five to seven days. IgG is present in both the
blood and tissues, and is the only antibody to cross the
placenta from the mother to the fetus. Maternal IgG
protects the newborn for the first months of life, until
the infant’s immune system produces its own
antibodies.
IgA constitutes approximately 15% of the immunoglobulins within the body. Although it is found to
some degree in the blood, it is present primarily in the
secretions of the respiratory and gastrointestinal tract,
in saliva, colostrum (the yellowish fluid produced by
the breasts during late pregnancy and the first few days
after childbirth), and in tears. IgA plays an important
role in defending the body against invasion of germs
through the mucous membrane-lined organs.
IgE is the antibody that causes acute allergic reactions; it is measured to detect allergic conditions. IgD,
which constitutes the smallest portion of the immunoglobulins, is rarely evaluated or detected, and its function is not well understood.

Preparation
This test requires a blood sample.

Aftercare
Because this test is ordered when either very low
or very high levels of immunoglobulins are suspected,
the patient should be alert for any signs of infection
1972

after the test, including fever, chills, rash, or skin
ulcers. Any bone pain or tenderness should also be
immediately reported to the physician.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or feeling lightheaded after venipuncture, or
bruising.

Normal results
Reference ranges vary from laboratory to laboratory and depend upon the method used. For adults,
normal values are usually found within the following ranges (1 mg = approximately 0.000035 oz. and
1 dL = approximately 0.33 oz.):


IgM: 60–290 mg/dL



IgG: 700–1,800 mg/dL



IgA: 70–440 mg/dL

Abnormal results
Increased IgM levels can indicate Waldenström’s
macroglobulinemia, a malignancy caused by secretion of IgM at high levels by malignant lymphoplasma cells. Increased IgM levels can also indicate
chronic infections, such as hepatitis or mononucleosis and autoimmune diseases, like rheumatoid
arthritis.
Decreased IgM levels can be indicative of AIDS,
immunosuppression caused by certain drugs like steroids or dextran, or leukemia.
Increased levels of IgG can indicate chronic liver
disease, autoimmune diseases, hyperimmunization
reactions, or certain chronic infections, such as tuberculosis or sarcoidosis.
Decreased levels of IgG can indicate WiskottAldrich syndrome, a genetic deficiency caused by
inadequate synthesis of IgG and other immunoglobulins. Decreased IgG can also be seen with AIDS and
leukemia.
Increased levels of IgA can indicate chronic liver
disease, chronic infections, or inflammatory bowel
disease.
Decreased levels of IgA can be found in ataxia,
a condition affecting balance and gait, limb or eye
movements, speech, and telangiectasia, an increase
in the size and number of the small blood vessels
in an area of skin, causing redness. Decreased
GALE ENCYCLOPEDIA OF MEDICINE

IgG is the most abundant of the classes of immunoglobulins. It is the antibody for viruses, bacteria, and
antitoxins. It is found in most tissues and plasma.

Antibody—A protein manufactured by the white
blood cells to neutralize an antigen in the body. In
some cases, excessive formation of antibodies
leads to illness, allergy, or autoimmune disorders.
Antigen—A substance that can cause an immune
response, resulting in production of an antibody, as
part of the body’s defense against infection and
disease. Many antigens are foreign proteins not
found naturally in the body, and include germs,
toxins, and tissues from another person used in
organ transplantation.



IgM is the first antibody present in an immune
response.



IgA is an early antibody for bacteria and viruses. It is
found in saliva, tears, and all other mucous
secretions.



IgD activity is not well understood.



IgE is present in the respiratory secretions. It is an
antibody for parasitic diseases, Hodgkin’s disease,
hay fever, atopic dermatitis, and allergic asthma.

Autoimmune disorder—A condition in which antibodies are formed against the body’s own tissues;
for example, in some forms of arthritis.

IgA levels are also seen in conditions of low blood
protein (hypoproteinemia), and drug immunosuppression.
Resources
BOOKS

Fischbach, Frances T. A Manual of Laboratory Diagnostic
Tests. Philadelphia: Lippincott Williams & Wilkins,
1999.
Pagana, Kathleen D., and Timothy J. Pagana. Mosby’s
Manual of Diagnostic and Laboratory Tests. St. Louis,
MO: Mosby, Inc., 1999.

Janis O. Flores

Immunoglobulin see Gammaglobulin

Immunoglobulin deficiency
syndromes
Definition
Immunoglobulin deficiency syndromes are a
group of immunodeficiency disorders in which the
patient has a reduced number of or lack of antibodies.

Description
Immunoglobulins (Ig) are antibodies. There are
five major classes of antibodies: IgG, IgM, IgA, IgD,
and IgE.
GALE ENCYCLOPEDIA OF MEDICINE

All antibodies are made by B-lymphocytes
(B-cells). Any disease that harms the development or
function of B-cells will cause a decrease in the amount
of antibodies produced. Since antibodies are essential
in fighting infectious diseases, people with immunoglobulin deficiency syndromes become ill more often.
However, the cellular immune system is still functional, so these patients are more prone to infection
caused by organisms usually controlled by antibodies.
Most of these invading germs (microbes) make capsules, a mechanism used to confuse the immune system. In a healthy body, antibodies can bind to the
capsule and overcome the bacteria’s defenses. The
bacteria that make capsules include the streptococci,
meningococci, and Haemophilus influenzae. These
organisms cause such diseases as otitis, sinusitis, pneumonia, meningitis, osteomyelitis, septic arthritis, and
sepsis. Patients with immunoglobulin deficiencies are
also prone to some viral infections, including echovirus, enterovirus, and hepatitis B. They may also
have a bad reaction to the attenuated version of the
polio virus vaccine.
There are two types of immunodeficiency diseases:
primary and secondary. Secondary disorders occur in
normally healthy bodies that are suffering from an
underlying disease. Once the disease is treated, the
immunodeficiency is reversed. Immunoglobulin deficiency syndromes are primary immunodeficiency diseases, occurring because of defective B-cells or
antibodies. They account for 50% of all primary immunodeficiencies, and they are, therefore, the most prevalent type of immunodeficiency disorders.


X-linked agammaglobulinemia is an inherited disease.
The defect is on the X chromosome and, consequently, this disease is seen more frequently in
males than females. The defect results in a failure of
B-cells to mature. Mature B-cells are capable of
making antibodies and developing ‘‘memory,’’ a feature in which the B-cell will rapidly recognize and
1973

Immunoglobulin deficiency syndromes



KEY TERMS

Immunoglobulin deficiency syndromes

respond to an infectious agent the next time it is
encountered. All classes of antibodies are decreased
in agammaglobulinemia.

KEY TERMS



Selective IgA deficiency is an inherited disease,
resulting from a failure of B-cells to switch from
making IgM, the early antibody, to IgA. Although
the B-cell numbers are normal, and the B-cells are
otherwise normal (they can still make all other
classes of antibodies), the amount of IgA produced
is limited. This results in more infections of mucosal
surfaces, such as the nose, throat, lungs, and
intestines.

Antibody—Another term for immunoglobulin. A
protein molecule that specifically recognizes and
attaches to infectious agents.
T-helper cell—A type of cell that recognizes foreign antigens and activates T- and B-cells in an
immune response.



Transient hypogammaglobulinemia of infancy is a
temporary disease of unknown cause. It is believed to
be caused by a defect in the development of T-helper
cells (cells that recognize foreign antigens and activate T- and B-cells in an immune response). As the
child ages, the number and condition of T-helper
cells improves and this situation corrects itself.
Hypogammaglobulinemia is characterized by low
levels of gammaglobulin (antibodies) in the blood.
During the disease period, patients have decreased
levels of IgG and IgA antibodies. In lab tests, the
antibodies that are present do not react well with
infectious bacteria.



Common variable immunodeficiency is a defect in
both B cells and T-lymphocytes. It results in a near
complete lack of antibodies in the blood.

of B lymphocytes (B-cells). There are two main points
in the development of B-cells when defects can occur.
First, B-cells can fail to develop into antibody-producing cells. X-linked agammaglobulinemia is an example
of this disease. Secondly, B-cells can fail to make a
particular type of antibody or fail to switch classes
during maturation. Initially, when B-cells start making
antibodies for the first time, they make IgM. As they
mature and develop memory, they switch to one of the
other four classes of antibodies. Failures in switching or
failure to make a subclass of antibody leads to immunoglobulin deficiency diseases. Another mechanism
that results in decreased antibody production is a defect
in T-helper cells. Generally, defects in T-helper cells are
listed as severe combined immunodeficiencies.



Ig heavy chain deletions is a genetic disease in which
part of the antibody molecule is not produced. It
results in the loss of several antibody classes and
subclasses, including most IgG antibodies and all
IgA and IgE antibodies. The disease occurs because
part of the gene for the heavy chain has been lost.



Selective IgG subclass deficiencies is a group of
genetic diseases in which some of the subclasses of
IgG are not made. There are four subclasses in the
IgG class of antibodies. As the B-cell matures, it can
switch from one subclass to another. In these diseases
there is a defect in the maturation of the B-cells that
results in a lack of switching.



IgG deficiency with hyper-IgM is a disease that
results when the B-cell fails to switch from making
IgM to IgG. This produces an increase in the amount
of IgM antibodies present and a decrease in the
amount of IgG antibodies. This disease is the result
of a genetic mutation.

Causes and symptoms
Immunoglobulin deficiencies are the result of congenital defects affecting the development and function
1974

Symptoms are persistent and frequent infections,
diarrhea, failure to thrive, and malabsorption (of
nutrients).

Diagnosis
An immunodeficiency disease is suspected
when children become ill frequently, especially
from the same organisms. The profile of organisms
that cause infection in patients with immunoglobulin deficiency syndrome is unique and is preliminary evidence for this disease. Laboratory tests are
performed to verify the diagnosis. Antibodies can
be found in the blood. Blood is collected and analyzed for the content and types of antibodies present. Depending on the type of immunoglobulin
deficiency the laboratory tests will show a decrease
or absence of antibodies or specific antibody
subclasses.

Treatment
Immunodeficiency diseases cannot be cured.
Patients are treated with antibiotics and immune serum.
Immune serum is a source of antibodies. Antibiotics are
useful for fighting bacteria infections. There are some
GALE ENCYCLOPEDIA OF MEDICINE

Bone marrow transplantation can, in most cases,
completely correct the immunodefiency.

Prognosis
Patients with immunoglobulin defiency syndromes must practice impeccable health maintenance
and care, paying particular attention to optimal dental
care, in order to stay in good health.
Resources
BOOKS

Berkow, Robert, editor. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 1997.

Jacqueline L. Longe

Immunoglobulin electrophoresis see
Immunoelectrophoresis
Immunoglobulins G, A, and M test see
Immunoelectrophoresis

Immunologic therapies
Definition
Immunologic therapy is the treatment of disease
using medicines that boost the body’s natural immune
response.

Purpose
Immunologic therapy is used to improve the
immune system’s natural ability to fight diseases such
as cancer, hepatitis and AIDS. These drugs may also
be used to help the body recover from immunosuppression resulting from treatments such as chemotherapy or radiation therapy.

Description
Most drugs in this category are synthetic versions of
substances produced naturally in the body. In their natural forms, these substances help defend the body
against disease. For example, aldesleukin (Proleukin) is
an artificially made form of interleukin-2, which helps
white blood cells work. Aldesleukin is administered to
patients with kidney cancers and skin cancers that have
GALE ENCYCLOPEDIA OF MEDICINE

spread to other parts of the body. Filgrastim
(Neupogen) and sargramostim (Leukine) are versions
of natural substances called colony stimulating factors,
which drive the bone marrow to make new white blood
cells. Another type of drug, epoetin (Epogen, Procrit), is
a synthetic version of human erythropoietin that stimulates the bone marrow to make new red blood cells.
Thrombopoietin stimulates the production of platelets,
disk-shaped bodies in the blood that are important in
clotting. Interferons are substances the body produces
naturally using immune cells to fight infections and
tumors. The synthetic interferons carry brand names
such as Alferon, Roferon or Intron A. Some of the
interferons that are currently in use as drugs are
Recombinant Interferon Alfa-2a, Recombinant
Interferon Alfa-2b, interferon alfa-n1 and Interferon
Alfa-n3. Alfa interferons are used to treat hairy cell
leukemia, malignant melanoma and AIDs-related
Kaposi’s sarcoma. In addition interferons are also used
for other conditions such as laryngeal papillomatosis,
genital warts and certain types of hepatitis.

Recommended dosage
The recommended dosage depends on the type of
immunologic therapy. For some medicines, the physician will decide the dosage for each patient, taking into
account a patient’s weight and whether he/she is taking other medicines. Some drugs used in immunologic
therapy are given only in a hospital, under a physician’s supervision. For those that patients may give
themselves, check with the physician who prescribed
the medicine or the pharmacist who filled the prescription for the correct dosage.
Most of these drugs come in injectable form.
These drugs are generally administered by the cancer
care provider.

Precautions
Aldesleukin
This medicine may temporarily increase the chance
of getting infections. It may also lower the number of
platelets in the blood, and thus possibly interfering with
the blood’s ability to clot. Taking these precautions
may reduce the chance of such problems:


Avoid people with infections, if possible.



Be alert to signs of infection, such as fever, chills, sore
throat, pain in the lower back or side, cough, hoarseness, or painful or difficulty with urination. If any of
these symptoms occur, get in touch with a physician
immediately.
1975

Immunologic therapies

drugs that are effective against fungi, but very few drugs
that are effective against viral diseases.

Immunologic therapies



Be alert to signs of bleeding problems, such as black,
tarry stools, tiny red spots on the skin, blood in the
urine or stools, or any other unusual bleeding or
bruising.



Take care to avoid cuts or other injuries. Be especially careful when using knives, razors, nail clippers
and other sharp objects. Check with a dentist for the
best ways to clean the teeth and mouth without
injuring the gums. Do not have dental work done
without checking with a physician.



Wash hands frequently, and avoid touching the eyes
or inside of the nose unless the hands have just been
washed.

Aldesleukin may make some medical conditions
worse, such as chickenpox, shingles (herpes zoster),
liver disease, lung disease, heart disease, underactive
thyroid, psoriasis, immune system problems and mental problems. The medicine may increase the chance of
seizures (convulsions) in people who are prone to
having them. Also, the drug’s effects may be greater
in people with kidney disease, because their kidneys are
slow to clear the medicine from their bodies.

Epoetin helps the body make new red blood cells,
but it is not effective unless there is adequate iron in
the body. The physician may recommend taking iron
supplements or certain vitamins that help supply the
body with iron. It is necessary to follow the physician’s
advice in this instance—recommendations for iron in
this case, as with any supplements should only come
from a physician.
In studies of laboratory animals, epoetin taken
during pregnancy caused birth defects, including
damage to the bones and spine. However, the drug
has not been reported to cause problems in human
babies whose mothers take it. Women who are pregnant or who may become pregnant should check
with their physicians for the most up-to-date information on the safety of taking this medicine during
pregnancy.
People with certain medical conditions may have
problems if they take this medicine. For example, the
chance of side effects may be greater in people with
high blood pressure, heart or blood vessel disease or a
history of blood clots. Epoetin may not work properly
in people who have bone problems or sickle cell
anemia.

Colony stimulating factors
Certain drugs used in treating cancer reduce the
body’s ability to fight infections. Although colony
stimulating factors help restore the body’s natural
defenses, the process takes time. Getting prompt treatment for infections is important, even while taking this
medicine. Call the physician at the first sign of illness
or infection, such as a sore throat, fever or chills.
People with certain medical conditions could have
problems if they take colony stimulating factors.
People who have kidney disease, liver disease or conditions caused by inflammation or immune system
problems can worsen these problems with colony stimulating factors. Those who have heart disease may
be more likely to experience side effects such as water
retention and heart rhythm problems while taking
these drugs. Finally, patients who have lung disease
might increase their chances of suffering from shortness of breath. Those who have any of these medical
conditions should check with their personal physicians
before using colony stimulating factors.
Epoetin
Epoetin is a medicine that may cause seizures
(convulsions), especially in people who are prone to
having them. No one who takes these drugs should
drive, use machines or do anything considered dangerous in case of a seizure.
1976

Interferons
Interferons can add to the effects of alcohol and
other drugs that slow down the central nervous system, such as antihistamines, cold medicine, allergy
medicine, sleep aids, medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants. They
may also add to the effects of anesthetics, including
those used for dental procedures. Those taking interferons should check with their physicians before taking any of the above.
Some people experience dizziness, unusual fatigue, or become less alert than usual while being treated with these drugs. Because of these possible
problems, anyone who takes these drugs should not
drive, use machines or do anything else considered
dangerous until they have determined how the drugs
affect them.
Interferons often cause flu-like symptoms,
including fever and chills. The physician who prescribes this medicine may recommend taking acetaminophen (Tylenol) before—and sometimes after—
each dose to keep the fever from getting too high. If
the physician recommends this, follow instructions
carefully.
Like aldesleukin, interferons may temporarily
increase the chance of getting infections and lower
the number of platelets in the blood, leading to
GALE ENCYCLOPEDIA OF MEDICINE

a hospital, where medical professionals can watch for
early signs of problems. Medical tests might be performed to check for unwanted effects.

People who have certain medical conditions may
have problems if they take interferons. For example,
the drugs may worsen some medical conditions,
including heart disease, kidney disease, liver disease,
lung disease, diabetes, bleeding problems and mental
problems. In people who have overactive immune
systems, these drugs can even increase the activity of
the immune system. People who have shingles or
chickenpox, or who have recently been exposed to
chickenpox may increase their risk of developing
severe problems in other parts of the body if they
take interferons. People with a history of seizures or
mental problems could at risk if taking interferon.

Anyone who has breathing problems, fever or
chills while being given aldesleukin should check
with a physician immediately.

In teenage women, interferons may cause changes
in the menstrual cycle. Young women should discuss
this possibility with their physicians. Older people may
be more sensitive to the effects of interferons. This
may increase the chance of side effects.
These drugs are not known to cause fetal death,
birth defects or other problems in humans when taken
during pregnancy. Women who are pregnant or who
may become pregnant should ask their physicians for
the latest information on the safety of taking these
drugs during pregnancy.
Women who are breastfeeding their babies may
need to stop while taking this medicine. Whether interferons pass into breast milk is not known. Because of
the chance of serious side effects to the baby, breastfeeding while taking interferon is discouraged. Check
with a physician for advice.
General precautions for all types of immunologic
therapy
Regular physician visits are necessary during
immunologic therapy treatment. This gives the
physician a chance to make sure the medicine is
working and to check for unwanted side effects.
Anyone who has had unusual reactions to drugs
used in immunologic therapy should let the physician
know before resuming the drugs. Any allergies to
foods, dyes, preservatives, or other substances should
also be reported.

Side effects
Aldesleukin
In addition to its helpful effects, this medicine may
cause serious side effects. Generally, it is given only in
GALE ENCYCLOPEDIA OF MEDICINE

Other side effects should be brought to a physician’s attention as soon as possible:


dizziness



drowsiness



confusion



agitation



depression



nausea and vomiting



diarrhea



sores in the mouth and on the lips



tingling of hands or feet



decrease in urination



unexplained weight gain of five or more pounds

Some side effects are usually temporary and do
not need medical attention unless they are bothersome. These include dry skin; itchy or burning skin
rash or redness followed by peeling; loss of appetite;
and a general feeling of illness or discomfort.
Colony stimulating factors
As this medicine starts to work, the patient might
experience mild pain in the lower back or hips. This is
nothing to cause undue concern, and will usually go
away within a few days. If the pain is intense or
causes discomfort, the physician may prescribe a
painkiller.
Other possible side effects include headache, joint
or muscle pain and skin rash or itching. These side
effects tend to disappear as the body adjusts to the
medicine, and do not need medical treatment. If they
continue, or they interfere with normal activities,
check with a physician.
Epoetin
This medicine may cause flu-like symptoms, such
as muscle aches, bone pain, fever, chills, shivering, and
sweating, within a few hours after it is taken. These
symptoms usually go away within 12 hours. If they do
not, or if they are troubling, check with a physician.
Other possible side effects that do not need medical
attention are diarrhea, nausea or vomiting and fatigue
or weakness.
1977

Immunologic therapies

clotting problems. To help prevent these problems,
follow the precautions for reducing the risk of infection and bleeding listed for aldesleukin.

Immunologic therapies

Certain side effects should be brought to a physician’s attention as soon as possible. These include
headache, vision problems, increased blood pressure,
fast heartbeat, weight gain and swelling of the face,
fingers, lower legs, ankles or feet.
Anyone who has chest pain or seizures after taking epoetin should seek professional emergency medical attention immediately.
Interferons
This medicine may cause temporary hair loss (alopecia). While upsetting, it is not a sign that something
is seriously wrong. The hair should grow back normally after treatment ends.
As the body adjusts to the medicine many other
side effects usually go away during treatment. These
include flu-like symptoms, taste alteration, loss of
appetite (anorexia), nausea and vomiting, skin rash,
and unusual fatigue. If these problems persist, or
if they interfere with normal life, check with a
physician.
A few more serious side effects should be brought
to a physician’s attention as soon as possible:


confusion



difficulty thinking or concentrating



nervousness



depression



sleep problems



numbness or tingling in the fingers, toes and face
General caution regarding side effects for all types
of immunologic therapy

Other side effects are possible with any type
of immunologic therapy. Anyone who has unusual
symptoms during or after treatment with these
drugs should should contact the physician
immediately.

Interactions
Anyone who has immunologic therapy should let
the physician know all other medicines being taken.
Some combinations of drugs may interact, that can
increase or decrease the effects of one or both drugs
or can increase the likelihood of side effects.
Consultation with a physician is highly recommended
to get the insight on whether the possible interactions
can interfere with drug therapy or cause harmful
effects.
1978

Immunoprevention
Considering that most of the biological modifiers
such as cytokines elicit immune response that inhibit
incipient tumors before they are clinically evident,
immunoprevention has been proposed as a recent
strategy for combating cancer. Treatment involving
immune molecules (such as cytokines) prepared
synthetically or that are not produced by the patients themselves is called as passive immunotherapy.
Conversely, a vaccine is a form of active immune therapy because it elicits an immune response in patients.
A cancer vaccine may be made of whole tumor cell or of
substances or fragments contained in the tumor called
antigens.
Newer types of immunologic therapy that are
still considered investigational as of 2003 include
cell-based therapies. Instead of using synthetic chemicals that resemble substances produced by the
body, cell-based therapies use modified stem cells or
dendritic cells as vaccines against cancer. Stem cells
are undifferentiated cells whose daughter cells can
develop into various types of specialized cells, while
dendritic cells are cells that are able to initiate and
modify the immune system’s responses to cancer by
activating B cells and T cells. Dendritic cells appear
to offer a promising new form of immunotherapy for
cancer.
Another investigational form of treatment is the
development of cell-free tumor-specific peptide vaccines. Peptides are subunits of protein molecules that
contain two or more amino acids. Peptide vaccines are
intended to induce responses in the patient’s T cells
that inhibit tumor growth. As of late 2003, however,
peptide-based tumor vaccines have been shown to
shrink cancerous tumors only in patients with limited
disease.

Adoptive immunotherapy
Adoptive immunotherapy involves stimulating T
lymphocytes by exposing them to tumor antigens.
These modified cells are grown in the laboratory
and then injected into patients. Since the cells taken
from a different individual for this purpose often
results in rejection, patients serve both as donor and
recipient of their own T cells. Adoptive immunotherapy is particularly effective in patients who have
received massive doses of radiation and chemotherapy. In such patients, therapy results in immunosuppression (weakened immune systems), making them
vulnerable to viral infections. For example, CMVspecific T cells can reduce the risk of cytomegalovirus
(CMV) infection in transplant patients.
GALE ENCYCLOPEDIA OF MEDICINE

AIDS—Acquired immune deficiency syndrome. A
disease caused by infection with the human
immunodeficiency virus (HIV). In people with
this disease, the immune system breaks down,
increasing vulnerability to other infections and
some types of cancer.
Bone marrow—Soft tissue that fills the hollow
centers of bones. Blood cells and platelets
(disk-shaped bodies in the blood that are important in clotting) are produced in the bone
marrow.
Chemotherapy—Treatment of an illness with chemical agents. The term usually is used to describe
the treatment of cancer with drugs.
Clot—A hard mass that forms when blood
coagulates.
Fetus—A developing baby inside the womb.
Hepatitis—Inflammation of the liver caused by a
virus, chemical, or drug.

PERIODICALS

Fishman, M. N., and S. J. Antonia. ‘‘Cell-Based Immune
Therapy for Metastatic Renal Cancer.’’ Expert Review
of Anticancer Therapy 3 (December 2003): 837–849.
‘‘Immunoprevention of Cancer: Is the time Ripe?’’ Cancer
Research 60 (May 15, 2000): 2571–2575.
National Cancer Institute. Treating Cancer with Vaccine
Therapy. June 29, 2001. <http://cancertrials.nci.nih
.gov/news/features/vaccine/html/page05.htm 2000>.
Nieda, M., M. Tomiyama, and K. Egawa. ‘‘Ex vivo
Enhancement of Antigen-Presenting Function of
Dendritic Cells and Its Application for DC-Based
Immunotherapy.’’ Human Cell 16 (December 2003):
199–204.
Paczesny, S., H. Ueno, J. Fay, et al. ‘‘Dendritic Cells as
Vectors for Immunotherapy of Cancer.’’ Seminars in
Cancer Biology 13 (December 2003): 439–447.
Rosenberg, S. A. ‘‘Progress in Human Tumor Immunology
and Immunotherapy.’’ Nature 411, no. 6835 (2001):
380–385.
Scheibenbogen, C., A. Letsch, A. Schmittel, et al. ‘‘Rational
Peptide-Based Tumour Vaccine Development and T
Cell Monitoring.’’ Seminars in Cancer Biology 13
(December 2003): 423–429.

Immune response—The body’s natural protective
reaction to disease and infection.

Nancy Ross-Flanigan
Kausalya Santhanam, PhD
Teresa G. Odle
Rebecca J. Frey, PhD

Immune system—The system that protects the
body against disease and infection through
immune responses.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or
illness.
Psoriasis—A skin disease that manifests itself with
itchy, scaly, red patches on the skin.
Seizure—A sudden attack, spasm, or convulsion.
Shingles—A disease caused by an infection with
the Herpes zoster virus—the same virus that causes
chickenpox. Symptoms of shingles include pain
and blisters along one nerve, usually on the face,
chest, stomach, or back.
Sickle cell anemia—An inherited disorder in
which red blood cells contain an abnormal
form of hemoglobin, a protein that carries oxygen. The abnormal form of hemoglobin causes
the red cells to become sickle-shaped. The misshapen cells may clog blood vessels, preventing
oxygen from reaching tissues and leading to
pain, blood clots and other problems. Sickle
cell anemia is most common in people of
African descent and in people from Italy,
Greece, India, and the Middle East.

GALE ENCYCLOPEDIA OF MEDICINE

Immunosuppressant drugs
Definition
Immunosuppressant drugs, also called anti-rejection
drugs, are used to prevent the body from rejecting a
transplanted organ.

Purpose
When an organ, such as a liver, a heart or a
kidney, is transplanted from one person (the donor)
into another (the recipient), the immune system of the
recipient triggers the same response against the new
organ it would have to any foreign material, setting off
a chain of events that can damage the transplanted
organ. This process is called rejection and it can occur
rapidly (acute rejection), or over a long period of time
(chronic rejection). Rejection can occur despite close
matching of the donated organ and the transplant
patient. Immunosuppressant drugs greatly decrease
1979

Immunosuppressant drugs

Resources

KEY TERMS

Immunosuppressant drugs

the risks of rejection, protecting the new organ and
preserving its function. These drugs act by blocking
the immune system so that it is less likely to react
against the transplanted organ. A wide variety of
drugs are available to achieve this aim but work in
different ways to reduce the risk of rejection.
In addition to being used to prevent organ rejection, immunosuppressant drugs are also used to treat
such severe skin disorders as psoriasis and such other
diseases as rheumatoid arthritis, Crohn’s disease
(chronic inflammation of the digestive tract) and
patchy hair loss (alopecia areata). Some of these conditions are termed ‘‘autoimmune’’ diseases, indicating
that the immune system is acting against the body
itself.



Some immunosuppressants are also used to treat a
variety of autoimmune diseases:


Azathioprine (Imuran) is used not only to prevent
organ rejection in kidney transplants, but also in
treatment of rheumatoid arthritis. It has been used
to treat chronic ulcerative colitis, but it has been of
limited value for this use.



Cyclosporin (Sandimmune, Neoral) is used in heart,
liver, kidney, pancreas, bone marrow and heart/lung
transplantation. The Neoral form has been used to
treat psoriasis and rheumatoid arthritis. The drug
has also been used for many other conditions including multiple sclerosis, diabetes and myesthenia
gravis.



Glatiramer acetate (Copaxone) is used in treatment
of relapsing-remitting multiple sclerosis. In one
study, glatiramer reduced the frequency of multiple
sclerosis attacks by 75% over a two-year period.



Mycopehnolate (CellCept) is used along with cyclosporin in kidney, liver and heart transplants. It has
also been used to prevent the kidney problems associated with lupus erythematosus.



Sirolimus (Rapamune) is used in combination with
other drugs including cyclosporin and corticosteroids, in kidney transplants. The drug is also used
for the treatment of psoriasis.

Description
Immunosuppressant drugs can be classified
according to their specific molecular mode of action.
The three main immunosuppressant drugs currently
used in organ transplantations are the following:






Cyclosporins (Neoral, Sandimmune, SangCya).
These drugs act by inhibiting T-cell activation, thus
preventing T-cells from attacking the transplanted
organ.
Azathioprines (Imuran). These drugs disrupt the
synthesis of DNA and RNA and cell division.
Corticosteroids such as prednisolone (Deltasone,
Orasone). These drugs suppress the inflammation
associated with transplant rejection.

Most patients are prescribed a combination of
drugs after their transplant, one from each of the
above main groups; for example cyclosporin,
azathioprine and prednisolone. Over a period of
time, the doses of each drug and the number of drugs
taken may be reduced as the risks of rejection decrease.
However, most patients need to take at least one
immunosuppressive for the rest of their lives.
Immunosuppressants can also be classified
depending on the specific transplant:


basiliximab (Simulect) is also used in combination
with such other drugs as cyclosporin and corticosteroids, in kidney transplants



daclizumab (Zenapax) is also used in combination
with such other drugs as cyclosporin and corticosteroids, in kidney transplants



muromonab CD3 (Orthoclone OKT3) is used,
along with cyclosporin, in kidney, liver and heart
transplants

1980

tacrolimus (Prograf ) is used in liver transplants
and is under study for kidney, bone marrow, heart,
pancreas, pancreatic island cell, and small bowel
transplantation

Recommended dosage
Immunosuppressant drugs are available only with
a physician’s prescription. They come in tablet, capsule, liquid and injectable forms.
The recommended dosage depends on the type
and form of immunosuppressant drug and the purpose for which it is being used. Doses may be different
for different patients. The prescribing physician or the
pharmacist who filled the prescription will advise on
correct dosage.
Taking immunosuppressant drugs exactly as
directed is very important. Smaller, larger or more
frequent doses should never be taken, and the drugs
should never be taken for longer than directed. The
physician will decide exactly how much of the medicine each patient needs. Blood tests often are necessary
to monitor the action of the drug.
The prescribing physician should be consulted
before stopping an immunosuppressant drug.
GALE ENCYCLOPEDIA OF MEDICINE

Seeing a physician regularly while taking immunosuppressant drugs is important. These regular checkups will allow the physician to make sure the drug is
working as it should and to watch for unwanted side
effects. These drugs are very powerful and can cause
serious side effects, such as high blood pressure, kidney
problems and liver problems. Some side effects may not
show up until years after the medicine is used. Anyone
who has been advised to take immunosuppressant
drugs should thoroughly discuss the risks and benefits
with the prescribing physician
Immunosuppressant drugs lower a person’s resistance to infection and can make infections harder to
treat. The drugs can also increase the chance of uncontrolled bleeding. Anyone who has a serious infection or
injury while taking immunosuppressant drugs should
get prompt medical attention and should make sure that
the treating physician knows about the immunosuppressant prescription. The prescribing physician should
be immediately informed if signs of infection, such as
fever or chills, cough or hoarseness, pain in the lower
back or side, or painful or difficult urination, bruising or
bleeding, blood in the urine, bloody or black, tarry
stools occur. Other ways of preventing infection and
injury include washing the hands frequently, avoiding
sports in which injuries may occur, and being careful
when using knives, razors, fingernail clippers or other
sharp objects. Avoiding contact with people who have
infections is also important. In addition, people who are
taking or have been taking immunosuppressant drugs
should not have immunizations, such as smallpox vaccinations, without checking with their physicians.
Because of their low resistance to infection, people taking these drugs might get the disease that the vaccine is
designed to prevent. People taking immunosuppressant
drugs also should avoid contact with anyone who has
taken the oral polio vaccine, as there is a chance the virus
could be passed on to them. Other people living in their
home should not take the oral polio vaccine.
Immunosuppressant drugs may cause the gums to
become tender and swollen or to bleed. If this happens,
a physician or dentist should be notified. Regular
brushing, flossing, cleaning and gum massage may
help prevent this problem. A dentist can provide
advice on how to clean the teeth and mouth without
causing injury.

taking these drugs, the prescribing physician should be
informed about any of these conditions:
ALLERGIES. Anyone who has had unusual reactions
to immunosuppressant drugs in the past should let his
or her physician know before taking the drugs again.
The physician should also be told about any allergies
to foods, dyes, preservatives, or other substances.
PREGNANCY. Azathioprine may cause birth defects
if used during pregnancy, or if either the male or female
is using it at time of conception. Anyone taking this
medicine should use a barrier method of birth control,
such as a diaphragm or condoms. Birth control pills
should not be used without a physician’s approval.
Women who become pregnant while taking this medicine should check with their physicians immediately.

The medicine’s effects have not been studied in
humans during pregnancy. Women who are pregnant
or who may become pregnant and who need to take
this medicine should check with their physicians.
BREASTFEEDING. Immunosuppressant drugs pass
into breast milk and may cause problems in nursing
babies whose mothers take it. Breastfeeding is not
recommended for women taking this medicine.
OTHER MEDICAL CONDITIONS. People who have
certain medical conditions may have problems if they
take immunosuppressant drugs. For example:


People who have shingles (herpes zoster) or chickenpox, or who have recently been exposed to chickenpox, may develop severe disease in other parts of
their bodies when they take these medicines.



The medicine’s effects may be greater in people with
kidney disease or liver disease, because their bodies
are slow to get rid of the medicine.



The effects of oral forms of this medicine may be
weakened in people with intestinal problems, because
the medicine cannot be absorbed into the body.

Before using immunosuppressant drugs, people
with these or other medical problems should make
sure their physicians are aware of their conditions.
USE OF CERTAIN MEDICINES. Taking immunosuppressant drugs with certain other drugs may affect the
way the drugs work or may increase the chance of side
effects.

Side effects
Special conditions
People who have certain medical conditions or
who are taking certain other medicines may have problems if they take immunosuppressant drugs. Before
GALE ENCYCLOPEDIA OF MEDICINE

Increased risk of infection is a common side effect of
all the immunosuppressant drugs. The immune system
protects the body from infections and when the immune
system is suppressed, infections are more likely. Taking
1981

Immunosuppressant drugs

Precautions

Immunosuppressant drugs

KEY TERMS
Antibody—Protein produced by the immune system
in response to the presence in the body of an antigen.
Antigen—Any substance or organism that is foreign
to the body. Examples of antigens are: bacteria, bacterial toxins, viruses, or other cells or proteins.

from foreign substances and organisms causing
infection and disease such as: bacteria, viruses,
fungi and parasites.

Autoimmune disease—A disease in which the
immune system is overactive and has lost the ability
to distinguish between self and non-self.

Immunosuppressive—Any agent that suppresses the
immune response of an individual.

Chronic—A word used to describe a long-lasting
condition. Chronic conditions often develop gradually and involve slow changes.
Corticosteroids—A class of drugs that are synthetic
versions of the cortisone produced by the body. They
rank among the most powerful anti-inflammatory
agents.
Cortisone—Glucocorticoid produced by the adrenal
cortex in response to stress. Cortisone is a steroid with
anti-inflammatory and immunosuppressive properties.
Inflammation—A process occurring in body tissues,
characterized by increased circulation and the accumulation of white blood cells. Inflammation also occurs
in such disorders as arthritis and causes harmful effects.
Inflammatory—Pertaining to inflammation.
Immune response—Physiological response of the
body controlled by the immune system that involves
the production of antibodies to fight off specific foreign substances or agents (antigens).
Immune system—The network of organs, cells, and
molecules that work together to defend the body

such antibiotics as co-trimoxazole prevents some of
these infections. Immunosuppressant drugs are also
associated with a slightly increased risk of cancer
because the immune system also plays a role in protecting the body against some forms of cancer. For example,
long-term use of immunosuppressant drugs carries an
increased risk of developing skin cancer as a result of the
combination of the drugs and exposure to sunlight.
Other side effects of immunosuppressant drugs are
minor and usually go away as the body adjusts to the
medicine. These include loss of appetite, nausea or
vomiting, increased hair growth, and trembling or shaking of the hands. Medical attention is not necessary
unless these side effects continue or cause problems.
The treating physician should be notified immediately if any of the following side effects occur:
1982

Immunosuppressant—Any chemical substance that
suppresses the immune response.

Immunosuppresive cytotoxic drugs—A class of
drugs that function by destroying cells and suppressing the immune response.
Lymphocyte—Lymphocytes are white blood cells
that participate in the immune response. The two
main groups are the B cells that have antibody molecules on their surface and T cells that destroy
antigens.
Psoriasis—A skin disease characterized by itchy,
scaly, red patches on the skin.
Rejection—Rejection occurs when the body recognizes a new transplanted organ as ‘‘foreign’’ and
turns on the immune system of the body.
T cells—Any of several lymphocytes that have
specific antigen receptors, and that are involved
in cell-mediated immunity and destruction of
antigen-bearing cells.
Transplantation—The removal of tissue from one
part of the body for implantation to another part of
the body; or the removal of tissue or an organ from
one individual and its implantation in another individual by surgery.



unusual tiredness or weakness



fever or chills



frequent need to urinate

Interactions
Immunosuppressant drugs may interact with
other medicines. When this happens, the effects of
one or both drugs may change or the risk of side effects
may be greater. Other drugs may also have an adverse
effect on immunosuppressant therapy. This is particularly important for patients taking cyclosporin or
tacrolimus. For example, some drugs can cause the
blood levels to rise, while others can cause the blood
levels to fall and it is important to avoid such contraindicated combinations. Other examples are:
GALE ENCYCLOPEDIA OF MEDICINE

The effects of azathioprine may be greater in people
who take allopurinol, a medicine used to treat gout.



A number of drugs, including female hormones
(estrogens), male hormones (androgens), the antifungal drug ketoconazole (Nizoral), the ulcer drug cimetidine (Tagamet) and the erythromycins (used to treat
infections), may increase the effects of cyclosporine.



When sirolimus is taken at the same time as cyclosporin, the blood levels of sirolimus may be increased
to a level where there are severe side effects.
Although these two drugs are usually used together,
the sirolimus should be taken four hours after the
dose of cyclosporin.



Tacrolimus is eliminated through the kidneys. When
the drug is used with other drugs that may harm the
kidneys, such as cyclosporin, the antibiotics gentamicin and amikacin, or the antifungal drug amphotericin B, blood levels of tacrolimus may be
increased. Careful kidney monitoring is essential
when tacrolimus is given with any drug that might
cause kidney damage.



The risk of cancer or infection may be greater when
immunosuppressant drugs are combined with certain other drugs which also lower the body’s ability
to fight disease and infection. These drugs include
corticosteroids such as prednisone; the anticancer
drugs chlorambucil (Leukeran), cyclophosphamide
(Cytoxan) and mercaptopurine (Purinethol); and
the monoclonal antibody muromonab-CD3
(Orthoclone), which also is used to prevent transplanted organ rejection.

Not every drug that may interact with immunosuppressant drugs is listed here. Anyone who takes
immunosuppressant drugs should let the physician
know all other medicines he or she is taking and
should ask whether the possible interactions can interfere with treatment.
Resources
BOOKS

Abbas, A. K., and A. H. Lichtman. Basic Immunology:
Functions and Disorders of the Immune System.
Philadelphia: W. B. Saunders Co., 2001.
Sompayrac, L. M. How the Immune System Works. Boston:
Blackwell Science, 1999.
Travers, P. Immunobiology: The Immune System in Health
and Disease. 5th edition. New York: Garland
Publishers, 2001.

Nancy Ross-Flanigan

Immunotherapy see Immunologic therapies
GALE ENCYCLOPEDIA OF MEDICINE

Impacted tooth
Definition
An impacted tooth is any tooth that is prevented
from reaching its normal position in the mouth by
tissue, bone, or another tooth.

Description
The teeth that most commonly become impacted
are the third molars, also called wisdom teeth. These
large teeth are the last to develop, beginning to form
when a person is about nine years old, but not breaking through the gum tissue until the late teens or early
twenties. By this time, the jaws have stopped growing
and may be too small to accommodate these four
additional teeth. As the wisdom teeth continue to
move, one or more may become impacted, either by
running into the teeth next to them or becoming
blocked within the jawbone or gum tissue. An
impacted tooth can cause further dental problems,
including infection of the gums, displacement of
other teeth, or decay. At least one wisdom tooth
becomes impacted in nine of every ten people.

Causes and Symptoms
The movement of an erupting wisdom tooth and
any subsequent impaction may produce pain at the
back of the jaw. Pain may also be the result of infection, either from decay in any exposed portion of the
tooth or from trapped food and plaque in the surrounding gum tissue. Infection typically produces an
unpleasant taste when biting down and bad breath.
Another source of pain may be pericoronitis, a gum
condition in which the crown of the incompletely
erupted tooth produces inflammation, redness, and
tenderness of the gums. Less common symptoms of
an impacted tooth are swollen lymph nodes in the
neck, difficulty opening the mouth, and prolonged
headache.

Diagnosis
Upon visual examination, the dentist may find
signs of infection or swelling in the area where the
tooth is present or only partially erupted. Dental
x rays are necessary to confirm tooth impaction.

Treatment
Because impacted teeth may cause dental problems with few if any symptoms to indicate damage,
1983

Impacted tooth



Impedance phlebography

Resources

KEY TERMS
Dry socket—A painful condition following tooth
extraction in which a blood clot does not properly
fill the empty socket, leaving the bone underneath
exposed to air and food.
Eruption—The process of a tooth breaking through
the gum tissue to grow into place in the mouth.

ORGANIZATIONS

American Association of Oral and Maxillofacial Surgeons.
9700 West Bryn Mawr Ave., Rosemont, IL 60018-5701.
(847) 678-6200. <http://www.aaoms.org>.

Bethany Thivierge

Extraction—The removal of a tooth from its socket
in the bone.
Pericoronitis—A gum condition in which irritation
and inflammation are produced by the crown of an
incompletely erupted tooth.
Wisdom tooth—One of the four last teeth on the
top and bottom rows of teeth. Also called a third
molar.

dentists commonly recommend the removal of all
wisdom teeth, preferably while the patient is still a
young adult. A dentist may perform an extraction
with forceps and local anesthetic if the tooth is
exposed and appears to be easily removable in one
piece. However, he or she may refer a difficult extraction to an oral surgeon, a specialist who administers
either nitrous oxide-oxygen (commonly called
‘‘laughing gas’’), an intravenous sedative, or a general anesthetic to alleviate any pain or discomfort
during the surgical procedure. Extracting an
impacted tooth typically requires cutting through
gum tissue to expose the tooth, and may require
removing portions of bone to free the tooth. The
tooth may have to be removed in pieces to minimize
destruction to the surrounding structures. The
extraction site may or may not require one or more
stitches to help the incision heal.

Prognosis
The prognosis is very good when impacted teeth
are removed from young healthy adults without complications. Potential complications include postoperative infection, temporary numbness from nerve
irritation, jaw fracture, and jaw joint pain. An additional condition which may develop is called dry
socket: when a blood clot does not properly form in
the empty tooth socket, or is disturbed by an oral
vacuum (such as from drinking through a straw or
smoking), the bone beneath the socket is painfully
exposed to air and food, and the extraction site heals
more slowly.
1984

Impedance phlebography
Definition
Impedance phlebography is a noninvasive test
that uses electrical monitoring to measure blood flow
in veins of the leg. Information from this test helps a
doctor to detect deep vein thrombosis (blood clots or
thrombophlebitis).

Purpose
Impedance phlebography may be done in order
to:


detect blood clots lodged in the deep veins of the leg



screen patients who are likely to have blood clots in
the leg



detect the source of blood clots in the lungs (pulmonary emboli)

Blood clots in the legs can lead to more serious
problems. If a clot breaks loose from a leg vein, it may
travel to the lungs and lodge in a blood vessel in the
lungs. Blood clots are more likely to occur in people
who have recently had leg injuries, surgery, cancer, or
a long period of bed rest.

Precautions
Because this test is not invasive, it can be done on
all patients. However, the accuracy of the results will
be affected if the patient does not breathe normally or
keep the leg muscles relaxed. Compression of the veins
because of pelvic tumors or decreased blood flow, due
to shock or any condition that reduces the amount of
blood the heart pumps, may also change the test
results.

Description
Impedance phlebography works by measuring the
resistance to the transmission of electrical energy
(impedance). This resistance changes depending on
GALE ENCYCLOPEDIA OF MEDICINE

Using conductive jelly, the examiner puts electrodes on the patient’s calf. These electrodes are connected to an instrument called a plethysmograph,
which records the changes in electrical resistance that
occur during the test.
The patient lies down and raises one leg at a 308
angle, so that the calf is above the level of the heart.
The examiner wraps a pressure cuff around the
patient’s thigh and inflates it to a pressure of 45–60
cm of water for 45 seconds. The plethysmograph
records the electrical changes that correspond to
changes in the volume of blood in the vein at the
time the pressure is exerted and again three seconds
after the cuff is deflated. This procedure is repeated
several times in both legs.
This test takes 30 to 45 minutes. Impedance phlebography is also called an impedance test of blood
flow or impedance plethysmography.

Preparation
Patients undergoing this test do not need to alter
their diet, change their normal activities, or stop taking any medications. They will wear a surgical gown
during the test, and be asked to urinate before the test
starts. If keeping the legs elevated causes discomfort,
mild pain medication will be given.

Aftercare
The patient may resume normal or postoperative
activities after the test.

Risks
Impedance phlebography is painless and safe. It
presents no risk to the patient.

Normal results
Normally, inflating the pressure cuff will cause a
sharp rise in the pressure in the veins of the calf
because blood flow is blocked. When the cuff is
released, the pressure decreases rapidly as the blood
flows away.

Abnormal results
If a clot is present, the pressure in the calf veins
will already be high. It does not become sharply higher
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Thrombophlebitis—Inflammation of a vein, associated with the formation of a blood clot.

when the pressure cuff is tightened. When the pressure
cuff is deflated, the clot blocks the flow of blood out of
the calf vein. The decrease in pressure is not as rapid as
when no clot is present, and the shape of the resulting
graph is different.
Resources
OTHER

Griffith, H. Winter. ‘‘Complete Guide to Medical Tests.’’
ThriveOnline. <http://thriveonline.oxygen.com>.

Tish Davidson, A.M.

Impedance plethysmography see Impedance
phlebography
Impedance test of blood flow see Impedance
phlebography

Impetigo
Definition
Impetigo refers to a very localized bacterial infection of the skin. There are two types, bullous and
epidemic.

Description
Impetigo is a skin infection that tends primarily to
afflict children. Impetigo caused by the bacterium
Staphylococcus aureus (also known as staph) affects
children of all ages. Impetigo caused by the bacteria
called group A streptococci (also know as strep) are
most common in children ages two to five.
The bacteria that cause impetigo are very contagious. They can be spread by a child from one part of
his or her body to another by scratching, or contact
with a towel, clothing, or stuffed animal. These same
methods can pass the bacteria on from one person to
another.
Impetigo tends to develop in areas of the skin that
have already been damaged through some other
1985

Impetigo

the volume of blood flowing through the veins. By
graphing the impedance, a doctor or technician can
tell whether a clot is obstructing blood flow.

Impetigo

mechanism (a cut or scrape, burn, insect bite, or vesicle
from chickenpox).

Causes and symptoms
The first sign of bullous impetigo is a large bump
on the skin with a clear, fluid-filled top (called a vesicle). The bump develops a scab-like, honey-colored
crust. There is usually no redness or pain, although
the area may be quite itchy. Ultimately, the skin in this
area will become dry and flake away. Bullous impetigo
is usually caused by staph bacteria.
Epidemic impetigo can be caused by staph or strep
bacteria, and (as the name implies) is very easily passed
among children. Certain factors, such as heat and
humidity, crowded conditions, and poor hygiene
increase the chance that this type of impetigo will spread
rapidly among large groups of children. This type of
impetigo involves the formation of a small vesicle surrounded by a circle of reddened skin. The vesicles
appear first on the face and legs. When a child has
several of these vesicles close together, they may spread
to one another. The skin surface may become eaten
away (ulcerated), leaving irritated pits. When there are
many of these deep, pitting ulcers, with pus in the center
and brownish-black scabs, the condition is called
ecthyma. If left untreated, the type of bacteria causing
this type of impetigo has the potential to cause a serious
kidney disease called glomerulonephritis. Even when
impetigo is initially caused by strep bacteria, the vesicles
are frequently secondarily infected with staph bacteria.
Impetigo is usually an uncomplicated skin condition. Left untreated, however, it may develop into a
serious disease, including osteomyelitis (bone infection),
septic arthritis ( joint infection), or pneumonia. If large
quantities of bacteria are present and begin circulating
in the bloodstream, the child is in danger of developing
an overwhelming systemic infection known as sepsis.

Diagnosis
Characteristic appearance of the skin is the usual
method of diagnosis, although fluid from the vesicles
can be cultured and then examined in an attempt to
identify the causative bacteria.

Treatment
Uncomplicated impetigo is usually treated with a
topical antibiotic cream called mupirocin. In more
serious, widespread cases of impetigo, or when the
child has a fever or swollen glands, antibiotics may be
1986

Impetigo is a contagious bacterial skin infection that mostly
affects the area around the nose and mouth. Usually caused by
staphylococci, this person’s impetigo was triggered by herpes
simplex. (Photo Researchers, Inc. Reproduced by permission.)

KEY TERMS
Systemic—Involving the whole body; the opposite
of localized.
Ulcer—An irritated pit in the surface of a tissue.
Vesicle—A bump on the skin filled with fluid.

given by mouth or even through a needle placed in a
vein (intravenously).

Prognosis
Prognosis for a child with impetigo is excellent.
The vast majority of children recover quickly, completely, and uneventfully.

Prevention
Prevention involves good hygiene. Handwashing;
never sharing towels, clothing, or stuffed animals; and
keeping fingernails well-trimmed are easy precautions
to take to avoid spreading the infection from one
person to another.
Resources
PERIODICALS

‘‘Bullous Impetigo.’’ Archives of Pediatrics and Adolescent
Medicine 151, no. 11 (November 1997): 1168+.

Rosalyn Carson-DeWitt, MD

Implant therapy see Radioactive implants
GALE ENCYCLOPEDIA OF MEDICINE

Definition
The implantable cardioverter-defibrillator is an
electronic device to treat life-threatening heartbeat
irregularities. It is surgically implanted.

Purpose
The implantable cardioverter-defibrillator is used
to detect and stop serious ventricular arrhythmias
and restore a normal heartbeat in people who are at
high risk of sudden death. The American Heart
Association recommends that implantable cardioverterdefibrillators only be considered for patients who
have a life-threatening arrhythmia. A recent study by
the National Heart, Lung, and Blood Institute demonstrated that implantable cardioverter-defibrillators
are the treatment of choice instead of drug therapy
for patients who have had a cardiac arrest or heart
attack and are at risk for developing ventricular tachycardia, which is a very rapid heartbeat, or ventricular
fibrillation, which is an ineffective, irregular heart
activity. Other studies suggest that 20% of these
high risk patients would die within two years without
an implantable cardioverter-defibrillator. With the
device, the five-year risk of sudden death drops to
five percent.

Precautions
The implantable cardioverter-defibrillator should
not be used on patients who faint from causes other
than a known life-threatening ventricular arrhythmia,
to treat slow heart rates, or during an emergency.

Description
According to the American College of
Cardiology, more than 80,000 Americans currently
have an implantable cardioverter-defibrillator;
17,000 of these were implanted in 1995 alone. The
battery-powered device rescues the patient from a
life-threatening arrhythmia by rapid pacing and/or
delivering electrical shock(s) to suspend heart activity
and then allow it to initiate a normal rhythm. Before
the development of the implantable cardioverterdefibrillator, most people who experienced ventricular
fibrillation and were not near a hospital with a well
equipped emergency team died within minutes.
The implantable cardioverter-defibrillator is like a
mini computer connected to the patient’s heart. Newer
GALE ENCYCLOPEDIA OF MEDICINE

X ray of implanted cardioverter-defibrillator (Custom Medical
Stock Photo. Reproduced by permission.)

models weigh less than 10 ounces and can be
implanted beneath the skin of the chest in the pectoral
region, without major surgery. A lead from the device
is then inserted into the heart through a vein. The
procedure is performed in an operating room under
general anesthesia. Earlier versions of implantable cardioverter-defibrillators were implanted in the abdomen and required open-chest surgery to connect the
electrodes to the left and right ventricles.
The implantable cardioverter-defibrillator is set
above the patient’s exercise heart rate. Once the device
is in place, many tests will be conducted to ensure that
the device is sensing and defibrillating properly. The
newer implantable cardioverter-defibrillators last
seven or eight years. Technology and procedures continue to evolve.

Preparation
Before the procedure, a complete medical history
and physical exam will be done. Electrocardiography,
special electrophysiologic testing, chest x ray, urinalysis, and a blood test are usually also required.

Aftercare
The patient is monitored for arrhythmias
and to ensure that the implantable cardioverterdefibrillator is working properly. The physician
also watches for signs of infection. Before the patient
leaves the hospital, the device is tested again. Antiarrhythmia drug therapy is necessary in more than
half of all patients with implantable cardioverterdefibrillators, but the number of drugs and the
dosages are usually reduced. Any time a significant
change in anti-arrhythmia medication is made, the
device will be tested again.
1987

Implantable cardioverter-defibrillator

Implantable cardioverterdefibrillator

Impotence

Resources

KEY TERMS
Arrhythmia—A variation of the normal rhythm of
the heartbeat.
Cardioverter—A device to apply electric shock to
the chest to convert an abnormal heartbeat into a
normal heartbeat.

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
Texas Heart Institute. Heart Information Service. PO Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Defibrillation—An electronic process which helps
re-establish a normal heart rhythm.
Ventricles—The two large lower chambers of the
heart which pump blood to the lungs and the rest of
the human body.
Ventricular fibrillation—An arrhythmia in which
the heart beats very fast but blood is not pumped
out to the body. Ventricular fibrillation can quickly
become fatal if not corrected.
Ventricular tachycardia—An arrhythmia in which
the heart rate is more than 100 beats per minute.

The patient is taught how the device works,
and that the shock it delivers will feel like a punch or
kick in the chest. The patient is told to notify his/
her physician when the implantable cardioverterdefibrillator delivers a shock, and to go to the emergency room if multiple shocks are sent within a short
period of time.
Although most patients with implantable cardioverter-defibrillators are glad that they have the
device and feel that it has extended their lives, they
do experience fear and anxiety. This stems from the
sensation of the shock(s), the unpredictable circumstances under which shock(s) occurs, and unknown
outcomes.

Risks
There can be serious complications to the
implantation of a cardioverter-defibrillator. These
include inflammation of the pericardium, the sac
that surrounds the heart; heart attack; congestive
heart failure; and post-operative stroke. Serious
infections can develop in the area around the device
while the patient is initially hospitalized or up to
several months later. Death due to the device’s failure
while being tested during surgery is an uncommon
risk. The risk of death from the implantation procedure is about the same as that for a pacemaker, less
than one percent. There are also potentially serious
risks associated with the device’s improper functioning once it is in place.
1988

Lori De Milto

Impotence
Definition
Impotence, often called erectile dysfunction, is the
inability to achieve or maintain an erection long
enough to engage in sexual intercourse.

Description
Under normal circumstances, when a man is sexually stimulated, his brain sends a message down the
spinal cord and into the nerves of the penis. The nerve
endings in the penis release chemical messengers,
called neurotransmitters, that signal the corpora
cavernosa (the two spongy rods of tissue that span
the length of the penis) to relax and fill with blood.
As they expand, the corpora cavernosa close off other
veins that would normally drain blood from the penis.
As the penis becomes engorged with blood, it enlarges
and stiffens, causing an erection. Problems with blood
vessels, nerves, or tissues of the penis can interfere with
an erection.

Causes and symptoms
It is estimated that up to 20 million American men
frequently suffer from impotence and that it strikes up
to half of all men between the ages of 40 and 70.
Doctors used to think that most cases of impotence
were psychological in origin, but they now recognize
that, at least in older men, physical causes may play a
primary role in 60% or more of all cases. In men over
the age of 60, the leading cause is atherosclerosis, or
narrowing of the arteries, which can restrict the flow of
blood to the penis. Injury or disease of the connective
tissue, such as Peyronie’s disease, may prevent the
corpora cavernosa from completely expanding.
Damage to the nerves of the penis, from certain types
of surgery or neurological conditions, such as
GALE ENCYCLOPEDIA OF MEDICINE

Certain types of blood pressure medications, antiulcer drugs, antihistamines, tranquilizers (especially
before intercourse), antifungals (hetoconazole), antipsychotics, antianxiety drugs, and antidepressants,
known as selective serotonin reuptake inhibitors
(SSRIs, including Prozac and Paxil), can interfere
with erectile function. Smoking, excessive alcohol consumption, and illicit drug use may also contribute. In
rare cases, low levels of the male hormone testosterone
may contribute to erectile failure. Finally, psychological factors, such as stress, guilt, or anxiety, may also
play a role, even when the impotence is primarily due
to organic causes.

Diagnosis
The doctor also obtains a thorough medical history
to find out about past pelvic surgery, diabetes, cardiovascular disease, kidney disease, and any medications
the man may be taking. The physical examination
should include a genital examination, a measurement
of blood flow through the penis, hormone tests, and a
glucose test for diabetes.
In some cases, nocturnal penile tumescence testing
is performed to find out whether the man has erections
while asleep. Healthy men usually have about four or
five erections throughout the night. The man applies a
device to the penis called a Rigiscan before going to
bed at night, and the device can determine whether he
has had erections. (If a man is able to have normal
erections at night, this suggests a psychological cause
for his impotence.)

Treatment
Years ago, the standard treatment for impotence
was an implantable penile prosthesis or long-term
psychotherapy. Although physical causes are now
more readily diagnosed and treated, individual or
marital counseling is still an effective treatment for
impotence when emotional factors play a role.
Fortunately, other approaches are now available to
treat the physical causes of impotence.
Medications
The first line and by far the most common treatment today is with the prescription drug sildenafil
citrate, sold under the brand name Viagra. An
GALE ENCYCLOPEDIA OF MEDICINE

estimated 20 million prescriptions for the pill
have been filled since it was approved by the FDA in
March 1998. It is also the most effective treatment
with a success rate of more than 60%. The drug boosts
levels of a substance called cyclic GMP, which
is responsible for widening the blood vessels of
the penis. In clinical studies, Viagra produced
headaches in 16% of men who took it, and other
side effects included flushing, indigestion, and stuffy
nose.
The primary drawback to Viagra, which works
about an hour after it is taken, it that the FDA cautions men with heart disease or low blood pressure to
be thoroughly examined by a physician before obtaining a prescription.
In the summer of 2002, two investigational drugs
were announced to become available in the near future
to also treat erectile dysfunction. Vardenafil and tadalafil both helped men who also had such conditions as
diabetes, high blood pressure and benign prostatic
hypertrophy. The drugs are awaiting final FDA
approval.
Vardenafil and tadalafil belong to the same group
of chemical compounds as sildenafil, namely phosphodiesterase type 5 (PDE-5) inhibitors. Some men
cannot benefit from sildenafil or the two newer PDE5 inhibitors because they have low levels of nitric
oxide. British investigators reported in late 2002 that
three different types of compounds are being studied
as possible medications for men with low levels of
nitric oxide. They are Rho-kinase inhibitors, soluble
guanylate cyclase activators, and nitric oxide-releasing
PDE-5 inhibitors.
Other medications under investigation as treatments for impotence are topical agents. Topical
means that they are applied externally to the skin
rather than being injected or taken by mouth. If
approved, these drugs would provide a noninvasive
alternative for men who cannot take sildenafil or
other oral medications for impotence.
Injection therapy involves injecting a substance
into the penis to enhance blood flow and cause an
erection. The Food and Drug Administration (FDA)
approved a drug called alprostadil (Caverject) for this
purpose in July of 1995. Alprostadil relaxes smooth
muscle tissue to enhance blood flow into the penis. It
must be injected shortly before intercourse. Another,
similar drug that is sometimes used is papaverine—not
yet been approved by the FDA for this use. Either
drug may sometimes cause painful erections or priapism (uncomfortable, prolonged erections) that must be
treated with a shot of epinephrine.
1989

Impotence

Parkinson’s disease or multiple sclerosis, may also
cause impotence. Men with diabetes are especially at
risk for impotence because of their high risk of both
atherosclerosis and a nerve disease called diabetic
neuropathy.

Impotence

Alprostadil may also be administered into the urethral opening of the penis. In MUSE (medical urethral
system for erection), the man inserts a thin tube the width
of a vermicelli noodle into his urethral opening and
presses down on a plunger to deliver a tiny pellet containing alprostadil into his penis. The drug takes about 10
minutes to work and the erection lasts about an hour.
The main side effect is a sensation of pain and burning in
the urethra, which can last about five to 15 minutes.
Mechanical and surgical treatments
Another approach is vacuum therapy. The man
inserts his penis into a clear plastic cylinder and uses a
pump to force air out of the cylinder. This forms a
partial vacuum around the penis, which helps to draw
blood into the corpora cavernosa. The man then places
a special ring over the base of the penis to trap the blood
inside it. The only side effect with this type of treatment
is occasional bruising if the vacuum is left on too long.
Implantable penile prostheses are usually considered a last resort for treating impotence. They are
implanted in the corpora cavernosa to make the
penis rigid without the need for blood flow. The semirigid type of prosthesis consists of a pair of flexible
silicone rods that can be bent up or down. This type of
device has a low failure rate but, unfortunately, it
causes the penis to always be erect, which can be
difficult to conceal under clothing.
The inflatable type of device consists of cylinders
that are implanted in the corpora cavernosa, a fluid
reservoir implanted in the abdomen, and a pump
placed in the scrotum. The man squeezes the pump
to move fluid into the cylinders and cause them to
become rigid. (He reverses the process by squeezing
the pump again.) While these devices allow for intermittent erections, they have a slightly higher malfunction rate than the silicon rods.
Men can return to sexual activity six to eight
weeks after implantation surgery. Since implants
affect the corpora cavernosa, they permanently take
away a man’s ability to have a natural erection.
In rare cases, if narrowed or diseased veins are
responsible for impotence, surgeons may reroute the
blood flow into the corpus cavernosa or remove leaking vessels. However, the success rate with these procedures has been very low, and they are still considered
experimental.
Gene therapy
A newer investigational approach to the treatment of erectile dysfunction is gene therapy. As of
1990

late 2002, several preclinical studies have shown promise, but none of the gene-based strategies so far have
yet been tested for safety.

Alternative treatment
A number of herbs have been promoted for treating impotence. The most widely touted herbs for
this purpose are Coryanthe yohimbe (available by
prescription as yohimbine, with the trade name
Yocon) and gingko (Gingko biloba), although neither
has been conclusively shown to help the condition in
controlled studies. In addition, gingko carries some
risk of abnormal blood clotting and should be avoided
by men taking blood thinners such as coumadin.
Other herbs promoted for treating impotence include
true unicorn root (Aletrius farinosa), saw palmetto
(Serenoa repens), ginseng (Panax ginseng), and Siberian
ginseng (Eleuthrococcus senticosus). Strychnos Nux
vomica has been recommended, especially when impotence is caused by excessive alcohol, cigarettes, or dietary
indiscretions, but it can be very toxic if taken improperly, so it should be used only under the strict supervision of a physician trained in its use.

Prognosis
With proper diagnosis, impotence can nearly always
be treated or managed successfully. Unfortunately,
fewer than 10% of impotent men seek treatment.

Prevention
There is no specific treatment to prevent impotence. Perhaps the most important measure is to maintain general good health and avoid atherosclerosis by
exercising regularly, controlling weight, controlling
hypertension and high cholesterol levels, and avoiding
smoking. Avoiding excessive alcohol intake may also
help.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Erectile Dysfunction.’’ Section 17, Chapter 220. In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Miller, Lucinda G., and Wallace J. Murray, editors. Herbal
Medicinals: A Clinician’s Guide. Binghamton, N.Y.:
Haworth Press, 1999.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II. ‘‘CAM Therapies for Specific Conditions:
Impotence.’’ New York: Simon & Schuster, 2002.

GALE ENCYCLOPEDIA OF MEDICINE

Alprostadil—A smooth muscle relaxant sometimes
injected into the penis or applied to the urethral
opening to treat impotence.
Atherosclerosis—A disorder in which plaques of
cholesterol, lipids, and other debris build up on
the inner walls of arteries, narrowing them.
Corpus cavernosum (plural, corpora cavernosa)—
One of two rods of spongy tissue in the penis that
become engorged with blood in order to produce
an erection.
Gene therapy—A menthod of treating a disorder by
replacing damaged or abnormal genes with normal
ones. Some researchers think that gene therapy
may offer a new way to treat impotence.
Neurotransmitters—Chemicals that modify or
help transmit impulses between nerve synapses.
Papaverine—A smooth muscle relaxant sometimes
injected into the penis as a treatment for impotence.
Peyronie’s disease—A disease resulting from scarring of the corpus cavernosa, causing painful
erections.
Topical—A type of medication that is applied to a
specific and limited area of skin, and affects only
the area to which it is applied.

Gresser, U., and C. H. Gleiter. ‘‘Erectile Dysfunction:
Comparison of Efficacy and Side Effects of the PDE-5
Inhibitors Sildenafil, Vardenafil and Tadalafil—
Review of the Literature.’’ European Journal of Medical
Research 7 (October 29, 2002): 435–446.
‘‘Is Viagra Safe?’’ Internal Medicine Alert June 29, 2002: 90.
Norton, Patrice G.W. ‘‘Investigational Drugs in Erectile
Dysfunction. (Vardenafil, Tadalafil).’’ Internal
Medicine News June 1, 2002: 50.
Yap, R. L., and K. T. McVary. ‘‘Topical Agents and Erectile
Dysfunction: Is There a Place?’’ Current Urology
Reports 3 (December 2002): 471–476.
‘‘Yohimbe Tree Bark: Herbal Viagra Better Gotten by Rx.’’
Environmental Nutrition February 1999: 8.
ORGANIZATIONS

American Foundation for Urologic Disease. 1128 North
Charles Street, Baltimore, MD 21201. (410) 468-1800.
American Urological Association (AUA). 1120 North
Charles Street, Baltimore, MD 21201. (410) 727-1100.
<www.auanet.org>.
Center for Biologics Evaluation and Research (CBER),
U. S. Food and Drug Administration (FDA). 1401
Rockville Pike, Rockville, MD 20852-1448. (800)
835-4709 or (301) 827-1800. <www.fda.gov/cber>.
Impotence Institute of America, Impotents Anonymous.
10400 Little Patuxent Parkway, Suite 485, Columbia,
MD 21044-3502. (800) 669-1603.
National Kidney and Urologic Diseases Information
Clearinghouse. 3 Information Way, Bethesda, MD
20892-3580. (800) 891-5390.

Urethra—The small tube that drains urine from the
bladder, as well as serving as a conduit for semen
during ejaculation in men.
Viagra—Trade name of an orally administered drug
for erectile failure first cleared for marketing in the
United States in March 1998. Its generic name is
sildenafil citrate.

Ken R. Wells
Rebecca J. Frey, PhD

Impulse control disorders
Definition

PERIODICALS

Campbell, Adam. ‘‘Soft Science: The Exclusive World on
Which Sex Supplements may Help and Which Won’t.’’
Men’s Health May 2002: 100.
Cellek, S., R. W. Rees, and J. Kalsi. ‘‘A Rho-Kinase
Inhibitor, Soluble Guanylate Cyclase Activator and
Nitric Oxide-Releasing PDE5 Inhibitor: Novel
Approaches to Erectile Dysfunction.’’ Expert Opinion
on Investigational Drugs 11 (November 2002): 1563–
1573.
Christ, G. J. ‘‘Gene Therapy for Erectile Dysfunction:
Where Is It Going?’’ Current Opinion in Urology 12
(November 2002): 497–501.
Cowley, Geoffrey. ‘‘Looking Beyond Viagra.’’ Newsweek
April 24, 2000: 77.
GALE ENCYCLOPEDIA OF MEDICINE

Impulse control disorders are characterized by an
inability to resist the impulse to perform an action that
is harmful to one’s self or others. This is a relatively
new class of personality disorders, and the most common of these are intermittent explosive disorder, kleptomania, pyromania, compulsive gambling disorder,
and trichotillomania.

Description
All of these impulse control disorders involve the
loss or lack of control in certain specific situations.
The hallmark of these disorders is the individual’s
inability to stop impulses that may cause harm to
themselves or others. Affected individuals often feel
1991

Impulse control disorders

KEY TERMS

Impulse control disorders

anxiety or tension in considering these behaviors. This
anxiety or tension is relieved or diminished once the
action is performed.
Intermittent explosive disorder is more common
among men, and involves aggressive outbursts that
lead to assaults on others or destruction of property.
These outburst are unprovoked or seem to be out of
proportion to the event that precedes them.

attribute the connection to the high levels of serotonin
(a neurotransmitter) produced by carcinoid tumors.

Diagnosis
A diagnosis of any of these impulse control disorders can be made only after other medical and psychiatric disorders that may cause the same symptoms
have been ruled out.

Kleptomania is more common among women,
and involves the theft of objects that are seemingly
worthless. The act of stealing relieves tension and is
seen by the individual to be rewarding. The actual
stealing is not preplanned, and the concept of punishment for the crime does not occur to these individuals,
although they are aware that what they are doing is
wrong.

Some doctors may administer questionnaires or
similar psychiatric screeners as part of the differential
diagnosis. Two instruments that have been devised in
the early 2000s to specifically target impulsive behavior are the Gambling Urge Scale (GUS) and the
Lifetime History of Impulsive Behaviors (LHIB)
Interview.

Pyromania is more common among men, and
involves setting fires in order to feel pleasure and
relieve tension.

Intermittent explosive disorder involves severe
acts of assault or destruction of property. The aggression seen during these acts is vastly out of proportion
to events that may seem to have precipitated the acts.

Pathological gambling occurs in roughly 1-3% of
the population, and involves excessive gambling
despite heavy monetary losses. These losses actually
act as a motivating factor in continuing gambling in
order to recoup some of what was lost.
Trichotillomania involves pulling hair from one’s
own scalp, face, or body, and is more common in
women. It often begins in childhood, and is often
associated with major depression or attention-deficit/
hyperactivity disorder.

Causes and symptoms
The exact causes of impulse control disorders are
not fully understood as of 2004. Individuals who have
had serious head injuries, however, can be at a higher
risk for developing impulse control disorders, as are
those with epilepsy.
Some cases of impulse control disorders appear to
be side effects of general medical conditions. As of
2004, several groups of researchers have noted that
some older adults with Parkinson’s disease become
compulsive gamblers as the disease progresses. It is
thought that this gambling behavior is a side effect of
dopaminergic drugs, as it does not respond to standard treatments for compulsive gambling but only to
changes in the patient’s medication.
Another medical condition that is associated with
impulse control disorders is carcinoid syndrome. In
one group of 20 consecutive patients with the syndrome, 75% met DSM-IV diagnostic criteria for one
or another impulse control disorder. The researchers
1992

Kleptomania involves stealing objects that are
unnecessary and of little monetary value. The act of
stealing is not an expression of anger or vengeance.
Again, there is an increased tension before the act is
committed, and this is resolved or relieved once the
object is stolen.
Pyromania is classified by the deliberate setting of
fires more than once. The individual will exhibit a
fascination and attraction to fire and any objects associated with it. Before the fire is set, there is tension,
with a resolving relief once the fire is set. Acts of true
pyromania are not done for monetary gain, to express
anger, to conceal criminal behavior, or in response to
hallucination.
Pathological gambling is a disorder to gamble
despite continuing losses and monetary insufficiency.
This disorder typically begins in youth, and affected
individuals are often competitive, easily bored, restless, and generous.
For a diagnosis of pathological gambling, five or
more of the following symptoms must be present:


a preoccupation with gambling



a need to gamble with more money to achieve the
thrill of winning



repeated attempts to control or stop gambling



irritability or restlessness due to repeated attempts of
control



gambling as an escape from stress



lying to cover up gambling
GALE ENCYCLOPEDIA OF MEDICINE

Carcinoid syndrome—The pattern of symptoms
(often including asthma and diarrhea) associated
with carcinoid tumors of the digestive tract or
lungs.
Compulsive gambling disorder—An impulse control disorder in which an individual cannot resist
gambling despite repeated losses.
Intermittent explosive disorder—A personality
disorder in which an individual is prone to intermittent explosive episodes of aggression during
which he or she causes bodily harm or destroys
property.
Kleptomania—An impulse control disorder in
which one steals objects that are of little or no
value.
Pyromania—An impulse control disorder in which
one sets fires.
Trichotillomania—An impulse or compulsion to
pull out one’s own hair.

These disorders can usually be controlled with
medication, although it may need to be continued
long-term to help prevent further aggressive outbursts.
Long-term counseling is usually necessary as well.
Support groups and meetings may also help these
individuals.
The prognosis for intermittent explosive disorder,
kleptomania, and pyromania is fair. Little is known
about the prognosis for trichotillomania, and studies
have shown that the condition can disappear for long
periods (months to years) without any psychological
counseling. For pathological gambling, the prognosis
varies greatly from person to person. While total cure
for this condition is unlikely, much like alcoholism,
long periods of abstinence or continuous abstinence
are possible.

Prevention
There are no known preventive treatments or
measures for impulse control disorders.
Resources



conducting illegal activities, such as embezzling or
fraud, to finance gambling



losing a job or personal relationship due to gambling



borrowing money to fund gambling

Trichotillomania is the continuous pulling out of
one’s own hair. Again, there is an increased sense of
tension before pulling the hair, which is relieved once it
is pulled out. Recurrent pulling out of one’s hair
resulting in noticeable hair loss. Affected individuals
can undergo significant distress and impaired social,
occupational, and functional behavior.

Treatment
A combination of psychological counseling and
medication are the preferred treatments for the
impulse control disorders. For kleptomania, pyromania, and trichotillomania, behavior modification is
usually the treatment of choice. Children with trichotillomania are often helped by antidepressant medication. For pathological gambling, treatment usually
involves an adaptation of the model set forth by
Alcoholics Anonymous. Individuals are counseled
with the goal of eventual response to appropriate
social limits. In the case of intermittent explosive disorder, anger management and medication may be used
in extreme cases of aggression.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, D.C.: American Psychiatric Association,
2000.
PERIODICALS

Avanzi, M., E. Uber, and F. Bonfa. ‘‘Pathological Gambling
in Two Patients on Dopamine Replacement Therapy
for Parkinson’s Disease.’’ Neurological Sciences 25
(June 2004): 98–101.
Kurlan, R. ‘‘Disabling Repetitive Behaviors in Parkinson’s
Disease.’’ Movement Disorders 19 (April 2004):
433–437.
Raylu, N., and T. P. Oei. ‘‘The Gambling Urge Scale:
Development, Confirmatory Factor Validation, and
Psychometric Properties.’’ Psychology of Addictive
Behaviors 18 (June 2004): 100–105.
Russo, S., J. C. Boon, I. P. Kema, et al. ‘‘Patients with
Carcinoid Syndrome Exhibit Symptoms of Aggressive
Impulse Dysregulation.’’ Psychosomatic Medicine 66
(May-June 2004): 422–425.
Schmidt, C. A., A. E. Fallon, and E. F. Coccaro.
‘‘Assessment of Behavioral and Cognitive Impulsivity:
Development and Validation of the Lifetime History of
Impulsive Behaviors Interview.’’ Psychiatry Research
126 (April 30, 2004): 107–121.
Tay, Y. K., M. L. Levy, and D. W. Metry. ‘‘Trichotillomania
in Childhood: Case Series and Review.’’ Pediatrics 113
(May 2004): 494–498.

1993

Impulse control disorders

Prognosis

KEY TERMS

In vitro fertilization

Precautions

ORGANIZATIONS

American Psychiatric Association. 1400 K Street, NW,
Washington, DC 20005. <http://www.psych.org>.
Gamblers Anonymous International Service Office. PO Box
17173, Los Angeles, CA 90017. (213) 386-8789, Fax:
(213) 386-0030. <http://www.gamblersanonymous.
org/>.
National Institute of Mental Health. 6001 Executive
Boulevard, Room 8184, MSC 9663, Bethesda, MD
20892-9663. (301) 443-4513. <http://
www.nimh.nih.gov>.
Trichotillomania Learning Center, Inc. 1215 Mission Street,
Suite 2, Santa Cruz, CA 95060. (831) 457-1004, Fax:
(831) 426-4383. <http://www.trich.org>.

Liz Meszaros
Rebecca Frey, PhD

In vitro fertilization
Definition
In vitro fertilization (IVF) is a procedure in which
eggs (ova) from a woman’s ovary are removed. They
are fertilized with sperm in a laboratory procedure,
and then the fertilized egg (embryo) is returned to the
woman’s uterus.

Purpose
IVF is one of several assisted reproductive techniques (ART) used to help infertile couples to conceive a
child. If after one year of having sexual intercourse
without the use of birth control a woman is unable to
get pregnant, infertility is suspected. Some of the reasons for infertility are damaged or blocked fallopian
tubes, hormonal imbalance, or endometriosis in the
woman. In the man, low sperm count or poor quality
sperm can cause infertility.
IVF is one of several possible methods to increase
the chance for an infertile couple to become pregnant.
Its use depends on the reason for infertility. IVF may
be an option if there is a blockage in the fallopian tube
or endometriosis in the woman or low sperm count or
poor quality sperm in the man. There are other possible treatments for these conditions, such as surgery for
blocked tubes or endometriosis, which may be tried
before IVF.
IVF will not work for a woman who is not capable
of ovulating or a man who is not able to produce at
least a few healthy sperm.
1994

The screening procedures and treatments for infertility can become a long, expensive, and sometimes,
disappointing process. Each IVF attempt takes at
least an entire menstrual cycle and can cost $5,000$10,000, which may or may not be covered by health
insurance. The anxiety of dealing with infertility can
challenge both individuals and their relationship. The
added stress and expense of multiple clinic visits, testing, treatments, and surgical procedures can become
overwhelming. Couples may want to receive counseling
and support throughout the process.

Description
In vitro fertilization is a procedure where the joining of egg and sperm takes place outside of the
woman’s body. A woman may be given fertility
drugs before this procedure so that several eggs
mature in the ovaries at the same time. Eggs (ova)
are removed from a woman’s ovaries using a long,
thin needle. The physician gains access to the ovaries
using one of two possible procedures. One procedure
involves inserting the needle through the vagina
(transvaginally). The physician guides the needle to
the location of the ovaries with the help of an ultrasound machine. In the other procedure, called laparoscopy, a small thin tube with a viewing lens is inserted
through an incision in the navel. This allows the physician to see inside the patient, and locate the ovaries,
on a video monitor.
Once the eggs are removed, they are mixed with
sperm in a laboratory dish or test tube. (This is where
the term test tube baby comes from.) The eggs are
monitored for several days. Once there is evidence
that fertilization has occurred and the cells begin to
divide, they are then returned to the woman’s uterus.
In the procedure to remove eggs, enough may be
gathered to be frozen and saved (either fertilized or
unfertilized) for additional IVF attempts. A 2004
study from the Mayo Clinic found that frozen sperm
was as effective as fresh sperm for IVF.
IVF has been used successfully since 1978, when
the first child to be conceived by this method was born
in England. Over the past 20 years, thousands of couples have used this method of ART or similar procedures to conceive.
Other types of assisted reproductive technologies
might be used to achieve pregnancy. A procedure called
intracytoplasmic sperm injection (ICSI) uses a manipulation technique that must be performed using a
microscope to inject a single sperm into each egg. The
GALE ENCYCLOPEDIA OF MEDICINE

University of London’s St. George Hospital Medical
School, earning his physician’s license in 1939 and becoming a member of the Royal College of Surgeons. When
Steptoe volunteered as a naval surgeon during World War
II, he was captured and held as a prisoner until his release in
1943. Following his release, Steptoe studied obstetrics and
gynecology and moved to Manchester to start a private
practice in 1948. In 1951, Steptoe accepted a position at
Oldham General and District Hospital in England.
During his time at Oldham, Steoptoe continued his
study of fertility problems. Using a laparoscope, he developed a method to remove eggs from a woman’s ovaries. In
1966, Steptoe teamed with physiologist Robert G. Edwards
who had successfully fertilized eggs outside of the body. In
1968, the pair had a breakthrough when Edwards successfully fertilized an egg that Steptoe had removed, but their
attempts to implant the embryo failed repeatedly.
However, Steptoe and Edwards experienced success
when a fertilized egg was implanted into the uterus of
Leslie Brown. Brown gave birth to a healthy baby girl on
July 25, 1978.
(Archive. Reproduced by permission.)

Patrick Christopher Steptoe was born in Oxfordshire,
England, on June 9, 1913. His mother was a social worker
and his father was a church organist. Steptoe entered the

fertilized eggs can then be returned to the uterus, as in
IVF. In gamete intrafallopian tube transfer (GIFT) the
eggs and sperm are mixed in a narrow tube and then
deposited in the fallopian tube, where fertilization
normally takes place. Another variation on IVF is
zygote intrafallopian tube transfer (ZIFT). As in
IVF, the fertilization of the eggs occurs in a laboratory dish. And, similar to GIFT, the embryos are
placed in the fallopian tube (rather than the uterus
as with IVF).

Preparation
Once a woman is determined to be a good candidate for in vitro fertilization, she will generally be
given ‘‘fertility drugs’’ to stimulate ovulation and the
development of multiple eggs. These drugs may
include gonadotropin releasing hormone agonists
(GnRHa), Pergonal, Clomid, or human chorionic
gonadotropin (hcg). The maturation of the eggs is
then monitored with ultrasound tests and frequent
blood tests. If enough eggs mature, the physician will
perform the procedure to remove them. The woman
GALE ENCYCLOPEDIA OF MEDICINE

Steptoe retired and built a clinic in Cambridge. He and
Edwards were named Commanders of the British Empire,
and Steptoe was honored with fellowship in the Royal
Society. He and his wife had two children. Steptoe died
on March 21, 1988.

may be given a sedative prior to the procedure. A local
anesthetic agent may also be used to reduce discomfort during the procedure.

Aftercare
After the IVF procedure is performed the woman
can resume normal activities. A pregnancy test can be
done approximately 12–14 days later to determine if
the procedure was successful.

Risks
The risks associated with in vitro fertilization
include the possibility of multiple pregnancy (since
several embryos may be implanted) and ectopic pregnancy (an embryo that implants in the fallopian tube
or in the abdominal cavity outside the uterus). There is
a slight risk of ovarian rupture, bleeding, infections,
and complications of anesthesia. If the procedure is
successful and pregnancy is achieved, the pregnancy
would carry the same risks as any pregnancy achieved
without assisted technology.
1995

In vitro fertilization

P A T R I C K C H R I S T O P H E R S T E P T O E (1913–1988)

Inclusion conjunctivitis

KEY TERMS
Fallopian tubes—In a woman’s reproductive system, a pair of narrow tubes that carry the egg from
the ovary to the uterus.
GIFT—Stands for gamete intrafallopian tube transfer. This is a process where eggs are taken from a
woman’s ovaries, mixed with sperm, and then
deposited into the woman’s fallopian tube.
ICSI—Stands for intracytoplasmic sperm injection.
This process is used to inject a single sperm into
each egg before the fertilized eggs are put back into
the woman’s body. The procedure may be used if
the male has a low sperm count.
ZIFT—Stands for zygote intrafallopian tube transfer. In this process of in vitro fertilization, the eggs
are fertilized in a laboratory dish and then placed in
the woman’s fallopian tube.

92354. (909) 796-4851. <http://www.llu.edu/llumc/
fertility>.
Resolve. 1310 Broadway, Somerville, MA 02144-1731. (617)
623-0744. <http://www.resolve.org>.
OTHER

‘‘Infertility.’’ HealthWorld Online Page. <http://
www.healthy.net>.
‘‘In vitro Fertilization: A Teacher’s Guide from Newton’s
Apple.’’ PBS Page. <http://www.pbs.org/ktca/newtons/11/invitro.html>.

Altha Roberts Edgren
Teresa G. Odle

Inclusion blennorrhea see Inclusion
conjunctivitis

Inclusion conjunctivitis
Normal results
Success rates vary widely between clinics and
between physicians performing the procedure and
implantation does not guarantee pregnancy. Therefore,
the procedure may have to be repeated more than once
to achieve pregnancy. However, success rates have
improved in recent years, up from 20% in 1995 to 27%
in 2001.

Abnormal results
An ectopic or multiple pregnancy may abort
spontaneously or may require termination if the health
of the mother is at risk. The number of multiple pregnancies has decreased in recent years as technical
advances and professional guidelines have led to
implanting of fewer embryos per attempt.
Resources
PERIODICALS

‘‘Frozen, Fresh Sperm Both Effective for In Vitro
Fertilization.’’ Obesity, Fitness & Wellness Week June 5,
2004: 1059.
‘‘Multiple Births Via In Vitro Fertilization Are Declining.’’
Women’s Health Weekly May 6, 2004: 16.
ORGANIZATIONS

American Society for Reproductive Medicine. 1209
Montgomery Highway, Birmingham, AL 35216-2809.
(205) 978-5000. <asrm@asrm.com> <http://
www.asrm.com>.
Center for Fertility and In Vitro Fertilization Loma Linda
University. 11370 Anderson St., Loma Linda, CA
1996

Definition
Inclusion conjunctivitis is an inflammation of the
conjunctiva (the membrane that lines the eyelids and
covers the white part, or sclera, of the eyeball) by
Chlamydia trachomatis. Chlamydia is a sexually transmitted organism.

Description
Inclusion conjunctivitis, known as neonatal inclusion conjunctivitis in the newborn and adult inclusion
conjunctivitis in the adult, is also called inclusion
blennorrhea, chlamydial conjunctivitis, or swimming
pool conjunctivitis. This disease affects four of 1,000
(0.4%) live births. Approximately half of the infants
born to untreated infected mothers will develop the
disease.

Causes and symptoms
Inclusion conjunctivitis in the newborn results
from passage through an infected birth canal and
develops 5–14 days after birth. Both eyelids and conjunctivae are swollen. There may be a discharge of pus
from the eyes.
Most instances of adult inclusion conjunctivitis
result from exposure to infected genital secretions. It
is transmitted to the eye by fingers and occasionally by
the water in swimming pools, poorly chlorinated hot
tubs, or by sharing makeup. In adult inclusion conjunctivitis, one eye is usually involved, with a stringy
discharge of mucus and pus. There may be little bumps
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Inclusion conjunctivitis is usually considered when
the patient has a follicular conjunctivitis that will not go
away, even after using topical antibiotics. Diagnosis
depends upon tests performed on the discharge from
the eye. Gram stains determine the type of microorganism, while culture and sensitivity tests determine which
antibiotic will kill the harmful microorganism.
Conjuntival scraping determines whether chlamydia is
present in cells taken from the conjunctiva.

KEY TERMS
Cervicitis—Cervicitis is an inflammation of the cervix or neck of the uterus.
Conjunctiva—The conjunctiva is the membrane
that lines the eyelids and covers the white part of
the eyeball (sclera).
Cornea—The clear dome-shaped structure that
covers the colored part of the eye (iris).
Neovascularization—Neovascularization is the
growth of new blood vessels.
Urethritis—Urethritis is an inflammation of the
urethra, the canal for the discharge of urine that
extends from the bladder to the outside of the body.

Treatment
Treatment in the newborn consists of administration of tetracycline ointment to the conjunctiva and
erythromycin orally or through intravenous therapy
for fourteen days. The mother should be treated for
cervicitis and the father for urethritis, even if they do
not have symptoms of these diseases.

vaginitis, pelvic inflammatory disease, or urethritis.
Patients with symptoms of these diseases should be
treated by a physician.

In adults, tetracycline ointment or drops should
be applied to the conjunctiva and oral tetracycline,
amoxacillin, or erythromycin should be taken for
three weeks, or doxycycline for one week.

Newell, Frank W. Ophthalmology: Principles and Concepts.
8th ed. St. Louis: Mosby, 1996.

Patients should have weekly checkups so the doctor can monitor the healing.
Oral tetracycline should not be administered to
children whose permanent teeth have not erupted. It
should also not be given to nursing or pregnant women.

Resources
BOOKS

ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
PO Box 7424, San Francisco, CA 94120-7424. <http://
www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.

Lorraine Steefel, RN

Prognosis
Untreated inclusion conjunctivitis in the newborn
persists for 3–12 months and usually heals; however,
there may be scarring or neovascularization. In the
adult, if left untreated, the disease may continue for
months and cause corneal neovascularization. Even if
treated, antibiotics usually do not reverse damage that
may have occurred, but they may help prevent it if
given early enough.

Prevention
The neonatal infection may be prevented by instilling erythromycin ointment in the conjunctival culde-sac at birth. It is not prevented by silver nitrate.
Chlamydia is a contagious, sexually transmitted
disease. Some systemic symptoms include a history of
GALE ENCYCLOPEDIA OF MEDICINE

Incompetent cervix
Definition
A cervix (the structure at the bottom of the uterus)
that is incompetent is abnormally weak, and therefore
it can gradually widen during pregnancy. Left
untreated, this can result in repeated pregnancy losses
or premature delivery.

Description
Incompetent cervix is the result of an anatomical
abnormality. Normally, the cervix remains closed
1997

Incompetent cervix

called follicles inside the lower eyelid and the eye is red.
Occasionally, the condition damages the cornea, causing cloudy areas and a growth of new blood vessels
(neovascularization).

Incompetent cervix

throughout pregnancy until labor begins. An incompetent cervix gradually opens due to the pressure from
the developing fetus after about the 13th week of
pregnancy. The cervix begins to thin out and widen
without any contractions or labor. The membranes
surrounding the fetus bulge down into the opening of
the cervix until they break, resulting in the loss of the
baby or a very premature delivery.

Causes and symptoms
Some factors that can contribute to the chance of
a woman having an incompetent cervix include
trauma to the cervix, physical abnormality of the cervix, or having been exposed to the drug diethylstilbestrol (DES) in the mother’s womb. Some women have
cervical incompetence for no obvious reason.

Diagnosis
Incompetent cervix is suspected when a woman
has three consecutive spontaneous pregnancy losses
during the second trimester (the fourth, fifth and
sixth months of the pregnancy). The likelihood of
this happening by random chance is less than 1%.
Spontaneous losses due to incompetent cervix account
for 20–25% of all second trimester losses. A spontaneous second trimester pregnancy loss is different
from a miscarriage, which usually happens during
the first three months of pregnancy.
The physician can check for abnormalities in the
cervix by performing a manual examination or by an
ultrasound test. The physician can also check to see if
the cervix is prematurely widened (dilated). Because
incompetent cervix is only one of several potential
causes for this, the patient’s past history of pregnancy
losses must also be considered when making the
diagnosis.

Treatment
Treatment for incompetent cervix is a surgical
procedure called cervical cerclage. A stitch (suture) is
used to tie the cervix shut to give it more support. It is
most effective if it is performed somewhere between
14–16 weeks into the pregnancy. The stitch is removed
near the end of pregnancy to allow for a normal birth.
Cervical cerclage can be performed under spinal,
epidural, or general anesthesia. The patient will need to
stay in the hospital for one or more days. The procedure to remove the suture is done without the need for
anesthesia. The vagina is held open with an instrument
called a speculum and the stitch is cut and removed.
1998

KEY TERMS
Diethylstilbestrol (DES)—DES is a drug given to
women a generation ago to prevent miscarriage.
At that time it was not known that female children
born of women who had been given DES would
show a higher rate for cervical and other reproductive abnormalities, as well as a rare form of vaginal
cancer, when they reached reproductive age.
Effacement—The thinning out of the cervix that
normally occurs along with dilation shortly before
delivery.
Preterm labor—Labor before the thirty-seventh
week of pregnancy.

This may be slightly uncomfortable, but should not be
painful.
Some possible risks of cerclage are premature
rupture of the amniotic membranes, infection of the
amniotic sac, and preterm labor. The risk of infection
of the amniotic sac increases as the pregnancy progresses. For a cervix that is dilated 3 centimeters (cm),
the risk is 30%.
After cerclage, a woman will be monitored for any
preterm labor. The woman needs to consult her obstetrician immediately if there are any signs of
contractions.
Cervical cerclage can not be performed if a
woman is more than 4 cm dilated, if the fetus has
already died in her uterus, or if her amniotic membranes are torn and her water has broken.

Prognosis
The success rate for cerclage correction of incompetent cervix is good. About 80-90% of the time
women deliver healthy infants. The success rate is
higher for cerclage done early in pregnancy.
Resources
OTHER

Weiss, Robin. ‘‘Incompetent Cervix.’’ The Mining Co. Guide
to Pregnancy/Childbirth Page. March 1998. <http://
www.pregnancy.miningco.com/library/weekly/
aa011298.htm>.

Tish Davidson, A.M.

Incontinence see Urinary incontinence
GALE ENCYCLOPEDIA OF MEDICINE

Indigestion
Definition
Indigestion, which is sometimes called dyspepsia,
is a general term covering a group of nonspecific
symptoms in the digestive tract. It is often described
as a feeling of fullness, bloating, nausea, heartburn, or
gassy discomfort in the chest or abdomen. The symptoms develop during meals or shortly afterward. In
most cases, indigestion is a minor problem that often
clears up without professional treatment.

Description
Indigestion or dyspepsia is a widespread condition,
estimated to occur in 25% of the adult population
of the United States. Most people with indigestion
do not feel sick enough to see a doctor; nonetheless, it is a common reason for office visits.
About 3% of visits to primary care doctors are
for indigestion.

Causes and symptoms
Physical causes
The symptoms associated with indigestion have a
variety of possible physical causes, ranging from commonplace food items to serious systemic disorders:


Diet. Milk, milk products, alcoholic beverages, tea,
and coffee cause indigestion in some people because
they stimulate the stomach’s production of acid.



Medications. Certain prescription drugs as well as
over-the-counter medications can irritate the stomach lining. These medications include aspirin,
NSAIDs, some antibiotics, digoxin, theophylline,
corticosteroids, iron (ferrous sulfate), oral contraceptives, and tricyclic antidepressants.



Disorders of the pancreas and gallbladder. These
include inflammation of the gallbladder or pancreas,
cancer of the pancreas, and gallstones.



Intestinal parasites. Parasitic infections that cause
indigestion include amebiasis, fluke and tapeworm
infections, giardiasis, and strongyloidiasis.



Systemic disorders, including diabetes, thyroid disease, collagen vascular disease.



Cancers of the digestive tract.



Conditions associated with women’s reproductive
organs. These conditions include menstrual cramps,
pregnancy, and pelvic inflammatory disease.

GALE ENCYCLOPEDIA OF MEDICINE

Indigestion often accompanies an emotional
upset, because the part of the nervous system involved
in the so-called ‘‘fight-or-flight’’ response also affects
the digestive tract. People diagnosed with anxiety or
somatoform disorders frequently have problems with
indigestion. Many people in the general population,
however, will also experience heartburn, ‘‘butterflies
in the stomach,’’ or stomach cramps when they are in
upsetting situations–such as school examinations,
arguments with family members, crises in their workplace, and so on. Some people’s digestive systems
appear to react more intensely to emotional stress
due to hypersensitive nerve endings in their intestinal
tract.
Specific gastrointestinal disorders
In some cases, the patient’s description of the
symptoms suggests a specific digestive disorder as the
cause of the indigestion. Some doctors classify these
cases into three groups:
ESOPHAGITIS TYPE. Esophagitis is an inflammation of the tube that carries food from the throat to
the stomach (the esophagus). The tissues of the esophagus can become irritated by the flow (reflux) of
stomach acid backward into the lower part of the
esophagus. If the patient describes the indigestion in
terms of frequent or intense heartburn, the doctor will
consider gastroesophageal reflux disease (GERD) as a
possible cause. GERD is a common disorder in the
general population, affecting about 30% of adults.
PEPTIC ULCER TYPE. Patients who smoke and are
over 45 are more likely to have indigestion of the
peptic ulcer type. This group also includes people
who find that their indigestion is relieved by taking
antacids or eating a small amount of food. Patients in
this category are often found to have Helicobacter
pylori infections. H. pylori is a rod-shaped bacterium
that lives in the tissues of the stomach and causes
irritation of the mucous lining of the stomach walls.
Most people with H. pylori infections do not develop
chronic indigestion, but the organism appears to cause
peptic ulcer disease (PUD) in a vulnerable segment of
the population.
NONULCER TYPE. Most cases of chronic indigestion–as many as 65%–fall into this third category.
Nonulcer dyspepsia is sometimes called functional
dyspepsia because it appears to be related to abnormalities in the way that the stomach empties its contents
into the intestine. In some people, the stomach empties
either too slowly or too rapidly. In others, the stomach’s muscular contractions are irregular and

1999

Indigestion

Psychologic and emotional causes

Indigestion

uncoordinated. These disorders of stomach movement
(motility) may be caused by hypersensitive nerve endings in the stomach tissues. Patients in this group are
likely to be younger than 45 and have a history of
taking medications for anxiety or depression.

Diagnosis
Patient history
Because indigestion is a nonspecific set of symptoms, patients who feel sick enough to seek medical
attention are likely to go to their primary care doctor.
The history does not always point to an obvious diagnosis. The doctor can, however, use the process of
history-taking to evaluate the patient’s mood or emotional state in order to assess the possibility of a psychiatric disturbance. In addition, asking about the
location, intensity, timing, and recurrence of the indigestion can help the doctor weigh the different diagnostic possibilities.
An important part of the history-taking is asking
about symptoms that may indicate a serious illness.
These warning symptoms include:


Weight loss



Persistent vomiting



Difficulty or pain in swallowing



Vomiting blood or passing blood in the stools



Anemia.
Imaging studies

If the doctor thinks that the indigestion should be
investigated further, he or she will order an endoscopic
examination of the stomach. An endoscope is a slender
tube-shaped instrument that allows the doctor to look
at the lining of the patient’s stomach. If the patient has
indigestion of the esophagitis type or nonulcer type,
the stomach lining will appear normal. If the patient
has PUD, the doctor will be able to see breaks or
ulcerated areas in the tissue. He or she may also
order ultrasound imaging of the abdomen, or a radionuclide scan to evaluate the motility of the stomach.

having to take a tissue sample from the stomach. One
of these noninvasive tests is a blood test and the other
is a breath test.

Treatment
Since most cases of indigestion are not caused by
serious disorders, many doctors prefer to try medications and other treatment measures before ordering an
endoscopy.
Diet and stress management
Many patients benefit from the doctor’s reassurance that they do not have a serious or fatal disorder.
Cutting out alcoholic beverages and drinks containing
caffeine often helps. The patient may also be asked to
keep a record of food intake, daily schedule, and
symptom severity. Food diaries sometimes reveal psychologic or dietary factors that influence indigestion.
Medications
Patients with the esophagitis type of indigestion
are often treated with H2 antagonists. H2 antagonists
are drugs that block the secretion of stomach acid.
They include ranitidine (Zantac) and famotidine
(Pepcid).
Patients with motility disorders may be given prokinetic drugs. Prokinetic medications speed up
the emptying of the stomach and increase intestinal
motility. They include metoclopramide (Reglan) and
cisapride (Propulsid). These drugs relieve symptoms in
60–80% of patients.
Removal of H. pylori
It is not clear that patients with H. pylori infections who have not developed gastric ulcers need to
have the bacterium removed. Some studies indicate,
however, that these patients may benefit from antibiotic therapy.

Alternative treatment
Herbal medicine

Laboratory tests
BLOOD TESTS. If the patient is over 45, the doctor

will have the patient’s blood analyzed for a complete
blood cell count, measurements of liver enzyme levels,
electrolyte and serum calcium levels, and thyroid
function.
TESTS FOR HELICOBACTER PYLORI. Doctors can
now test patients for the presence of H. pylori without

2000

Practitioners of Chinese traditional herbal medicine might recommend medicines derived from peony
(Paeonia lactiflora), hibiscus (Hibiscus sabdariffa), or
hare’s ear (Bupleurum chinense) to treat indigestion.
Western herbalists are likely to prescribe fennel
(Foeniculum vulgare), lemon balm (Melissa officinalis),
or peppermint (Mentha piperita) to relieve stomach
cramps and heartburn.
GALE ENCYCLOPEDIA OF MEDICINE

Dyspepsia—Another name for indigestion.
Endoscope—A slender tubular instrument used to
examine the inside of the stomach.
Gastroesophageal reflux disease (GERD)—A disorder of the lower end of the esophagus, caused by
stomach acid flowing backward into the esophagus
and irritating the tissues.
H2 antagonist—A type of drug that relieves indigestion by reducing the production of stomach acid.
Heartburn—A popular term for an uncomfortable
burning sensation in the stomach and lower esophagus, sometimes caused by the reflux of small
amounts of stomach acid.
Helicobacter pylori—A gram- negative rod-shaped
bacterium that lives in the tissues of the stomach and
causes inflammation of the stomach lining.
Motility—The movement or capacity for movement of an organism or body organ. Indigestion is
sometimes caused by abnormal patterns in the
motility of the stomach.
Peptic ulcer disease (PUD)—A stomach disorder
marked by corrosion of the stomach lining due to
the acid in the digestive juices.
Prokinetic—A drug that works to speed up the
emptying of the stomach and the motility of the
intestines.
Reflux—The backward flow of a body fluid or
secretion. Indigestion is sometimes caused by the
reflux of stomach acid into the esophagus.

Most cases of mild indigestion do not need medical treatment. For patients who consult a doctor and
are given an endoscopic examination, 5-15% are diagnosed with GERD and 15-25% with PUD. About 1%
of patients who are endoscoped have stomach cancer.
Most patients with functional dyspepsia do well on
either H2 antagonists or prokinetic drugs, depending
on the cause of their indigestion.

Prevention
Indigestion can often be prevented by attention to
one’s diet, general stress level, and ways of managing
stress. Specific preventive measures include:


Stop smoking.



Cutting down on or eliminating alcohol, tea, or
coffee.



Avoiding foods that are highly spiced or loaded
with fat.



Eating slowly and keeping mealtimes relaxed.



Practicing yoga or meditation.



Not taking aspirin or other medications on an empty
stomach.



Keeping one’s weight within normal limits.

Resources
OTHER

‘‘Indigestion.’’ ThriveOnline. April 6, 1998. <http://
thriveonline.oxygen.com>.

Rebecca J. Frey, PhD
Homeopathy
Homeopaths tailor their remedies to the patient’s
overall personality profile as well as the specific symptoms. Depending on the patient’s reaction to the indigestion and some of its likely causes, the homeopath
might choose Gelsemium (Gelsemium sempervirens),
Carbo vegetalis, Nux vomica, or Pulsatilla (Pulsatilla
nigricans).
Other treatments
Some alternative treatments are aimed at lowering
the patient’s stress level or changing attitudes and
beliefs that contribute to indigestion. These therapies
and practices include Reiki, reflexology, hydrotherapy,
therapeutic massage, yoga, and meditation.
GALE ENCYCLOPEDIA OF MEDICINE

Indinavir see Protease inhibitors
Indirect Coombs’ test see Coombs’ tests

Indium scan of the body
Definition
A scanning procedure in which a patient’s white
blood cells are first labeled with the radioactive substance indium, and then the patient’s body is scanned
as a way of tracking the white blood cells at the site of
possible infection.
2001

Indium scan of the body

Prognosis

KEY TERMS

Induction of labor

Normal results

KEY TERMS
Indium—A silvery metallic element with some
nonmetallic chemical properties used to label
white blood cells prior to scanning.
Leukocyte—A white blood cell protects the body
against infection and fight infection when it occurs.
They are bigger than red blood cells.

The scan should reveal no infection or pathology.

Abnormal results
The scan will reveal details, such as location,
about an infection in the patient’s body.
Carol A. Turkington

Purpose
The procedure is used to detect inflammatory
processes in the body such as infections. By labelling
the leukocytes (white blood cells), radiologists
or nuclear medicine specialists can then watch
their migration toward an abscess or other infection.

Induction of labor
Definition
Induction of labor involves using artificial means
to assist the mother in delivering her baby.

Description
A nuclear medicine technologist withdraws about
50 ml. of blood. White blood cells are collected,
exposed to indium, and reinjected by IV back into
the patient.
The scan is scheduled for between 18 and 24 hours
after the white blood cells have been labelled with
indium. (In some cases, more scanning may be scheduled 48 hours after labelling).
For the scan, the patient lies on a special scanning
table, as either a single camera passing underneath the
table or two cameras (one above the table and one
underneath) are placed as close as possible to the
body, slowly scanning the person’s body.
The radiologist may need extra pictures, but these
take only a few minutes each.
While the patient must remain perfectly still during the scan, there should be no discomfort.

Aftercare
After the scan, the patient should be able to continue with normal daily activities with no problems.

Risks
The only risk during this scanning procedure
could be to a patient who is pregnant, as with any
type of injectable radioactive substance. If the
woman is pregnant, the radiologist must be notified;
if the scan is cleared, the radiologist may use a lower
dosage of indium.
2002

Purpose
Labor is brought on, or induced, when the pregnancy has extended significantly beyond the expected
delivery date and the mother shows no signs of going
into labor. Generally, if the unborn baby is more than
two weeks past due, labor will be induced. In most
cases, a mother delivers her baby between 38–42 weeks
of pregnancy. This usually means that labor is induced
if the pregnancy has lasted more than 42 weeks. Labor
is also induced if the mother is suffering from diseases
(preeclampsia, chronic hypertension), if there is an Rh
blood incompatibility between the baby and the
mother, or if the mother or baby has a medical problem that requires delivery of the baby (like a premature rupture of the membranes).

Description
The uterus is the hollow female organ that supports the development and nourishment of the unborn
baby during pregnancy. Sometimes labor is induced
by the rupturing the amniotic membrane to release
amniotic fluid. This is an attempt to mimic the normal
process of ‘‘breaking water’’ that occurs early in the
normal birth process. This method is sometimes
enough stimulation to induce contractions in the
mother’s uterus. If labor fails to start, drugs are used.
Most labor is induced by using the drug Pitocin, a
synthetic form of oxytocin. Oxytocin is a natural hormone produced in the body by the pituitary gland.
During normal labor, oxytocin causes contractions.
When labor does not occur naturally, the doctor may
GALE ENCYCLOPEDIA OF MEDICINE

Cesarean section—Delivery of a baby through an
incision in the mother’s abdomen instead of
through the vagina; also called a C-section.
Preeclampsia—Hypertension (high blood pressure) experienced during pregnancy.
Rh blood incompatibility—A blood type problem
between mother (who is Rh negative) and baby
(who is Rh positive), making the immune system
of the mother attack her unborn baby. During delivery of the first pregnancy, the mother’s immune
system becomes sensitive to the Rh positive blood
of the baby. The mother’s system may then attack
later pregnancies and cause severe illness or death
to those babies.
Vasoconstriction—Constriction of a blood vessel.

baby’s heart rate is monitored by an electronic device
placed on top of the mother’s abdomen. The heart rate
is one sign that the unborn baby is getting enough
oxygen and remains healthy. Once the membranes
are broken, prolonged labor may result in infection
to either the newborn or the mother.

Normal results
Once labor is induced and the cervix has dilated,
labor usually proceeds normally. When performed
properly, induced labor is a safe procedure for both
mother and baby.
Resources
BOOKS

Berkow, Robert, et al., editors. The Merck Manual of
Medical Information. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.

John T. Lohr, PhD
give the mother Pitocin to start the contractions.
Pitocin makes the uterus contract with strength and
force almost immediately. This drug is given through a
vein in a steady flow that allows the doctor to control
the amount the mother is given.
Sometimes vaginal gels are used to induce labor.
Normally, the baby will pass through the opening of
the uterus (the cervix) into the birth canal during
delivery. Because of this, the cervix softens and begins
to enlarge (dilate) during the early part of labor to
make room for the baby to pass through. The cervix
will continue to dilate, and the contractions will eventually push the baby out of the mother’s body. When
labor needs to be induced, the cervix is often small,
hard, and not ready for the process. The doctor may
need to prepare or ‘‘ripen’’ the cervix to induce labor.
The hormone prostaglandin in a gel form may be
applied high in the vagina to soften and dilate the
cervix, making the area ready for labor. This may be
enough to stimulate contractions on its own. More
often, prostaglandin gel is used in conjunction with
Pitocin.
If all attempts to induce labor fail, a cesarean
section is performed.

Risks
Once labor has been induced, the unborn baby is
monitored to guard against a reduction in its oxygen
supply, or hypoxia. The drugs used to induce labor
cause vasoconstriction, which can decrease blood supply to the unborn baby. Throughout the process, the
GALE ENCYCLOPEDIA OF MEDICINE

Infant massage
Definition
Infant massage refers to massage therapy as specifically applied to infants. In most cases, oil or lotion
is used as it would be on an adult subject by a trained
and licensed massage therapist. Medical professionals
caring for infants might also use massage techniques
on infants born prematurely, on those with motor or
gastrointestinal problems, or on those who have been
exposed to cocaine in utero.

Purpose
Research from experiments conducted at the
Touch Research Institutes at the University of
Miami School of Medicine and Nova Southeastern
University has been cited for the clinical benefits
massage has on infants and children. Tiffany Field,
Ph. D., director, noted that the research ‘‘. . . suggests
that touch is as important to infants and children as
eating and sleeping. Touch therapy triggers many
physiological changes that help infants and children
grow and develop. For example, massage can stimulate nerves in the brain which facilitate food absorption, resulting in faster weight gain. It also lowers
level of stress hormones, resulting in improved
immune function.’’
2003

Infant massage

KEY TERMS

Infant massage

The benefits of infant massage include:


Relaxation



relief from stress



interaction with adults



stimulation of the nervous system

The results of several studies showed that infant
massage alleviates the stress that newborns experience as a result of the enormous change that birth
brings about in their lives after the 6–9 months they
have spent in the womb. Both premature infants and
full-term babies need the relaxation that comes from
massaging and moving their limbs and muscles. In
infants with colic, massage provides the relief necessary to disperse gas, ease muscle spasm, tone the
digestive system and help it work efficiently. Some
techniques even help bring relief from teething and
emotional stress. The stimulation an infant receives
from massage can aid circulation, strengthen muscles, help digestion, and relieve constipation. The
bonding that occurs with massage between a parent
and child enhances the entire process of bonding that
comes with contact through all of the senses, including touch, voice, and sight. It affords a physical
experience of quality time between the parents and
the child as well as with any significant others in a
baby’s life.

Description
Origins
The practice of massaging infants dates back to
ancient times, particularly in Asian and Pacific Island
cultures; that is, massage was a component of the
baby’s regular bath routine among the Maoris and
Hawaiians. Touch in these cultures is considered
healthful both physically and spiritually. In the West,
however, infant massage has received more attention
in recent years in conjunction with the popularity
of natural childbirth and midwife-assisted births.
Dr. Frédéric Leboyer, a French physician who was
one of the leaders of the natural childbirth movement,
helped to popularize infant massage through his
photojournalistic book on the Indian art of baby
massage.
Infant massage was introduced formally into
the United States in 1978 when Vimala Schneider
McClure, a yoga practitioner who served in an orphanage in Northern India, developed a training program
for instructors at the request of childbirth educators.
An early research study by R. Rice in 1976 had showed
that premature babies who were massaged surged
2004

ahead in weight gain and neurological development
over those who were not massaged. From McClure’s
training in India, her knowledge of Swedish massage
and reflexology, along with her knowledge of yoga
postures that she had already adapted for babies, she
became the foremost authority on infant massage. In
1986 she founded the International Association of
Infant Massage (IAIM), which has 27 chapters worldwide as of 2000.
Various techniques are used in infant massage,
with the different strokes specific to a particular therapy. Special handling is used for treating a baby with
gas and colic. Some of the strokes are known as ‘‘Indian
milking,’’ which is a gentle stroking of the child’s legs;
and the ‘‘twist and squeeze’’ stroke, a gentle squeeze of
the muscles in the thigh and calf. The light ‘‘feather’’
strokes often employed in regular Swedish massage are
applied at the end of a massage. The procedure is not
unlike certain forms of adult massage, but with extra
care taken for the fragility of the infant.
There are also specific Chinese techniques of
pediatric massage, including massage of children
with special needs. In China, these forms of massage
can be given by medical professionals, but parents are
often taught how to do the simpler forms for home
treatment of their children.

Preparations
If lotions or oils are used, care is taken to ensure
their safety on a baby’s delicate skin. The most important consideration is to use vegetable oils rather than
mineral oils, which can clog the pores in the skin. The
oil that is used should be warmed in the caregiver’s
hands before applying it to the baby’s skin. The environment in which the massage is given to an infant
should be comfortably warm, and as calm and nonthreatening as possible.

Precautions
Extreme caution is necessary when performing
infant massage. Strokes are made with the greatest
delicacy in order not to harm the infant in any way.
Proper techniques are taught by licensed massage
therapists ensuring that the infant is treated with
appropriate physical touch. Anyone who is unfamiliar
with handling a baby should receive appropriate
instruction before beginning infant massage.

Side effects
No adverse side effects have been reported when
infant massage is done properly after careful
GALE ENCYCLOPEDIA OF MEDICINE

Research and general acceptance
In addition to the study already noted regarding
touch therapy, a website devoted to infant massage
lists research published as early as 1969, and cites
hundreds of individual projects that have been conducted throughout the world focusing on infant massage. Many of the studies are related to the benefits of
massage and touch for premature infants and others
born with such risk factors as drug dependence.
Conclusions regarding the benefits are overwhelmingly positive. The proliferation of therapists
licensed in infant massage across the United States
and worldwide indicates that infant massage is
increasingly recognized as a legitimate health care
treatment.
Resources
BOOKS

Cline, Kyle. Chinese Massage for Infants and Children:
Traditional Techniques for Alleviating Colic, Teething
Pain, Earache, and Other Common Childhood
Conditions. Inner Traditions International, Limited,
1999.
Fan, Ya-Li. Chinese Pediatric Massage Therapy: Traditional
Techniques for Alleviating Colic, Colds, Earaches, and
Other Common Childhood Conditions, edited by Bob
Flaws. Blue Poppy Enterprises, 1999.
Gordon, Jay, and Brenda Adderly. Brighter Baby: Boosting
Your Child’s Intelligence, Health and Happiness through
Infant Therapeutic Massage. New York: Regnery
Publishing, Inc. 1999.
ORGANIZATIONS

International Association of Infant Massage. P.O. Box 1045.
Oak View, CA 93022.
International Institute of Infant Massage. 605 Bledsoe Rd.
NW. Albuquerque, NM 87107. (505) 341-9381. Fax:
(505) 341-9386. <http://www.infantmassage.com>.

Jane Spehar

Infant respiratory distress syndrome see
Respiratory distress syndrome
Infantile paralysis see Polio
Infarct avid imaging see Technetium heart
scan
Infarction see Stroke
GALE ENCYCLOPEDIA OF MEDICINE

Infection control
Definition
Infection control refers to policies and procedures
used to minimize the risk of spreading infections, especially in hospitals and human or animal health care
facilities.

Purpose
The purpose of infection control is to reduce the
occurrence of infectious diseases. These diseases are
usually caused by bacteria or viruses and can be spread
by human to human contact, animal to human contact, human contact with an infected surface, airborne
transmission through tiny droplets of infectious agents
suspended in the air, and, finally, by such common
vehicles as food or water. Diseases that are spread
from animals to humans are known as zoonoses; animals that carry disease agents from one host to
another are known as vectors.

Infection control in hospitals and other
health care settings
Infections contracted in hospitals are also called
nosocomial infections. They occur in approximately
5% of all hospital patients. These infections result in
increased time spent in the hospital and, in some cases,
death. There are many reasons nosocomial infections
are common, one of which is that many hospital
patients have a weakened immune system which
makes them more susceptible to infections. This weakened immune system can be caused either by the
patient’s diseases or by treatments given to the patient.
Second, many medical procedures can increase the
risk of infection by introducing infectious agents into
the patient. Thirdly, many patients are admitted to
hospitals because of infectious disease. These infectious agents can then be transferred from patient to
patient by hospital workers or visitors.
Infection control has become a formal discipline
in the United States since the 1950s, due to the spread
of staphylococcal infections in hospitals. Because
there is both the risk of health care providers acquiring infections themselves, and of them passing infections on to patients, the Centers for Disease Control
and Prevention (CDC) established guidelines for
infection control procedures. In addition to hospitals, infection control is important in nursing
homes, clinics, child care centers, and restaurants,
as well as in the home.
2005

Infection control

instruction, or by a licensed massage therapist who
specializes in infant care.

Infection control

ELIZABETH LEE HAZEN
(1885–1975)
Elizabeth Lee Hazen was born on August 24, 1885,
in Rich, Mississippi. Hazen, born the middle of three
children to Maggie (Harper) and William Edgar Hazen,
was orphaned before she turned four. She and her sister
went to live with their aunt and uncle shorly after her
younger brother died. Hazen attended the Mississippi
Industrial Institute and College at Columbus, receiving
her B.S. degree in 1910. During college, Hazen became
interested in science and she studied biology at
Columbia University, earning her M.S. in 1917. After
working in the U.S. Army laboratories during World
War I, she returned to Columbia where she received her
Ph.D. in microbiology in 1927. Following her work as an
instructor at Columbia, Hazen accepted a position with
the New York Department of Health where she
researched bacterial diseases.

Selected Infectious Diseases And Corresponding Treatment

Disease

Symptoms

Transmittal

Treatment

Chicken pox

Rash, lowgrade fever
Runny nose,
sore throat,
cough, fever,
headache,
muscle aches
Jaundice, flulike symptoms

Person to
person
Person to
person

None

Sexual contact
with an
infected person, contaminated blood,
food, or water
Air conditioning or water
systems

None

Person to
person

None

Person to
person

Antibiotics
for bacterial
meningitis,
hospital care
for viral
meningitis

Person to
person

Anti-inflammatory
drugs
Antifungal
drugs
applied
topically
Antibiotics,
antitoxins,
muscle
relaxers

Common
cold/
Influenza

Hepatitis

Legionnaire’s
Disease

Measles

In 1948, Hazen and Rachel Brown began researching fungal infections found in humans due to antibiotic
treatments and diseases. Some of the antibiotics they
discovered did indeed kill the fungus; however, they
also killed the test mice. Finally, Hazen located a microorganism on a farm in Virginia, and Brown’s tests indicated that the microorganism produced two antibiotics,
one of which proved effective for treating fungus and
candidiasis in humans. Brown purified the antibiotic
which was patented under the name nystatin. In 1954,
the antibiotic became available in pill form. Hazen and
Brown continued their research and discovered two
other antibiotics. Hazen received numerous awards individually and with her research partner, Rachel Brown.
Elizabeth Hazen passed away on June 24, 1975.

Meningitis

Mumps

Flu symptoms,
peneumonia,
diarrhea,
vomiting,
kidney failure,
respiratory
failure
Skin rash,
runny nose and
eyes, fever,
cough
Neck pain,
headache, pain
caused by
exposure to
light, fever,
nausea,
drowsiness
Swelling of
salivary glands

Ringworm

Skin rash

Contact with
infected animal or person

Tetanus

Lockjaw, other
spasms

Soil infection
of wounds

None

Antibiotics

To lower the risk of nosocomial infections, the
CDC began a national program of hospital inspection
in 1970 known as the National Nosocomial Infections
Surveillance system, or NNIS. The CDC reported that
over 300 hospitals participate in the NNIS system as of
the early 2000s. Data collected from the participating
hospitals show that infection control programs can
siginificantly improve patient safety, lower infection
rates, and lower patient mortality.

The newest addition to the infection control specialist’s resources is molecular typing, which speeds up
the identification of a disease agent. Rapid identification in turn allows for timely containment of a disease
outbreak.

Dental health care settings are similar to hospitals in
that both personnel and equipment can transmit infection if proper safeguards are not observed. The CDC
issued new guidelines in 2003 for the proper maintenance
and sterilization of dental equipment, hand hygiene for
dentists and dental hygienists, dental radiology, medications, and oral surgery, environmental infection control,
and standards for dental laboratories.

Due to constant changes in our lifestyles and
environments, new diseases are constantly appearing
that people are susceptible to, making protection from
the threat of infectious disease urgent. Many new
contagious diseases have been identified in the past
30 years, such as AIDS, Ebola, and hantavirus.
Increased travel between continents makes the worldwide spread of disease a bigger concern than it once

2006

Threat of emerging infectious diseases

GALE ENCYCLOPEDIA OF MEDICINE

The emergence of the severe acute respiratory syndrome (SARS) epidemic in Asia in February 2003 was
a classic instance of an emerging disease that spread
rapidly because of the increased frequency of international and intercontinental travel. In addition, the
SARS outbreak demonstrated the vulnerability of
hospitals and health care workers to emerging diseases. Clusters of cases within hospitals occurred in
the early weeks of the epidemic when the disease had
not yet been recognized and the first SARS patients
were admitted without isolation precautions.
The SARS epidemic also raised a number of ethical and legal questions regarding current attitudes
toward infection control.
Problems of antibiotic resistance
Because of the overuse of antibiotics, many bacteria have developed a resistance to common antibiotics. This means that newer antibiotics must
continually be developed in order to treat an infection.
However, further resistance seems to come about
almost simultaneously. This indicates to many scientists that it might become more and more difficult to
treat infectious diseases. The use of antibiotics outside
of medicine also contributes to increased antibiotic
resistance. One example of this is the use of antibiotics
in animal husbandry. These negative trends can only
be reversed by establishing a more rational use of
antibiotics through treatment guidelines.
Bioterrorism
The events of September 11, 2001, and the anthrax
scare that followed in October 2001 alerted public
health officials as well as the general public to the
possible use of infectious disease agents as weapons
of terrorism. The Centers for Disease Control and
Prevention (CDC) now has a list of topics and
resources related to bioterrorism on its web site.

Description
The goals of infection control programs are: immunizing against preventable diseases, defining precautions that can prevent exposure to infectious agents,
and restricting the exposure of health care workers to
an infectious agent. An infection control practitioner is
a specially trained professional, oftentimes a nurse, who
oversees infection control programs.
Commonly recommended precautions to avoid
and control the spread of infections include:
GALE ENCYCLOPEDIA OF MEDICINE



Vaccinate people and pets against diseases for which
a vaccine is available. As of 2003, the vaccines used
against infectious diseases are very safe compared to
most drugs.



Wash hands often.



Cook food thoroughly.



Use antibiotics only as directed.



See a doctor for infections that do not heal.



Avoid areas with a lot of insects.



Be cautious around wild or unfamiliar animals, or
any animals that are unusually aggressive. Do not
purchase exotic animals as pets.



Do not engage in unprotected sex or in intravenous
drug use.



Find out about infectious diseases when you make
travel plans. Travelers’ advisories and adult vaccination recommendations are available on the CDC web
site or by calling the CDC’s telephone service at
404-332-4559.

Because of the higher risk of spreading infectious
disease in a hospital setting, higher levels of precautions
are taken there. Typically, health care workers wear
gloves with all patients, since it is difficult to know
whether a transmittable disease is present or not.
Patients who have a known infectious disease are isolated to decrease the risk of transmitting the infectious
agent to another person. Hospital workers who come in
contact with infected patients must wear gloves and
gowns to decrease the risk of carrying the infectious
agent to other patients. All articles of equipment that
are used in an isolation room are decontaminated
before reuse. Patients who are immunocompromised
may be put in protective isolation to decrease the risk of
infectious agents being brought into their room. Any
hospital worker with infections, including colds, are
restricted from that room.
Hospital infections can also be transmitted
through the air. Thus care must be taken when handling infected materials so as to decrease the numbers of
infectious agents that become airborne. Special care
should also taken with hospital ventilation systems to
prevent recirculation of contaminated air.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Immunizations for Adults.’’ Section 13, Chapter 152. In
The Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
2007

Infection control

was. Additionally, many common infectious diseases
have become resistant to known treatments.

Infection control

KEY TERMS
Acquired immune deficiency syndrome (AIDS)—
A disease that weakens the body’s immune system.
It is also known as HIV infection.
Antibiotic—A substance, such as a drug, that can
stop a bacteria from growing or destroy the bacteria.
Antibiotic resistance—The ability of infectious
agents to change their biochemistry in such a way
as to make an antibiotic no longer effective.
Bioterrorism—The intentional use of diseasecausing microbes or other biologic agents to
intimidate or terrorize a civilian population for
political or military reasons.
Ebola—The disease caused by the newly described
and very deadly Ebola virus found in Africa.
Epidemiology—The branch of medicine that deals
with the transmission of infectious diseases in large
populations and with detection of the sources and
causes of epidemics.
Hantavirus—A group of arboviruses that cause
hemorrhagic fever (characterized by sudden onset,
fever, aching and bleeding in the internal organs).
Immunization—Immunity refers to the body’s ability to protect itself from a certain disease after it has
been exposed to that disease. Through immunization, also known as vaccination, a small amount of
an infectious agent is injected into the body to
stimulate the body to develop immunity.
Immunocompromized—Refers to the condition of
having a weakened immune system. This can happen due to genetic factors, drugs, or disease.
Nosocomial infection—An infection acquired in a
hospital setting.
Staphylococcal infection—An infection caused by
the organism Staphlococcus. Infection by this agent
is common and is often resistant to antibiotics.
Vector—An animal carrier that transfers an infectious organism from one host to another.
Zoonosis (plural, zoonoses)—Any disease of animals that can be transmitted to humans under natural conditions. Lyme disease, rabies, psittacosis
(parrot fever), cat-scratch fever, and monkeypox
are examples of zoonoses.

PERIODICALS

Ashford, D. A., R. M. Kaiser, M. E. Bales, et al. ‘‘Planning
Against Biological Terrorism: Lessons from Outbreak
2008

Investigations.’’ Emerging Infectious Diseases 9 (May
2003): 515–519.
Gostin, L. O., R. Bayer, and A. L. Fairchild. ‘‘Ethical and
Legal Challenges Posed by Severe Acute Respiratory
Syndrome: Implications for the Control of Severe
Infectious Disease Threats.’’ Journal of the American
Medical Association 290 (December 24, 2003):
3229–3237.
Ho, P. L., X. P. Tang, and W. H. Seto. ‘‘SARS: Hospital
Infection Control and Admission Strategies.’’
Respirology 8, Supplement (November 2003): S41–S45.
Jacobson, R. M., K. S. Zabel, and G. A. Poland. ‘‘The
Overall Safety Profile of Currently Available Vaccines
Directed Against Infectious Diseases.’’ Expert Opinion
on Drug Safety 2 (May 2003): 215–223.
Jarvis, W. R. ‘‘Benchmarking for Prevention: the Centers for
Disease Control and Prevention’s National
Nosocomial Infections Surveillance (NNIS) System
Experience.’’ Infection 31, Supplement 2 (December
2003): 44–48.
Kohn, W. G., A. S. Collins, J. L. Cleveland, et al.
‘‘Guidelines for Infection Control in Dental HealthCare Settings—2003.’’ Morbidity and Mortality Weekly
Reports: Reports and Recommendations 52, RR-17
(December 19, 2003): 1–61.
Peng, P. W., D. T. Wong, D. Bevan, and M. Gardam.
‘‘Infection Control and Anesthesia: Lessons Learned
from the Toronto SARS Outbreak.’’ Canadian Journal
of Anaesthesiology 50 (December 2003): 989–997.
Petrak, R. M., D. J. Sexton, M. L. Butera, et al. ‘‘The Value
of an Infectious Diseases Specialist.’’ Clinical Infectious
Diseases 36 (April 15, 2003): 1013–1017.
Sehulster, L., and R. Y. Chinn. ‘‘Guidelines for
Environmental Infection Control in Health-Care
Facilities. Recommendations of CDC and the
Healthcare Infection Control Practices Advisory
Committee (HICPAC).’’ Morbidity and Mortality
Recommendations and Reports 52, RR-10 (June 6,
2003): 1–42.
Subramanian, D., J. A. Sandoe, V. Keer, and M. H. Wilcox.
‘‘Rapid Spread of Penicillin-Resistant Streptococcus
pneumoniae Among High-Risk Hospital Inpatients and
the Role of Molecular Typing in Outbreak
Confirmation.’’ Journal of Hospital Infection 54 (June
2003): 99–103.
ORGANIZATIONS

American College of Epidemiology. 1500 Sunday Drive,
Suite 102, Raleigh, NC 27607. (919) 861-5573. <http://
www.acepidemiology.org>.
American Public Health Association (APHA). 800 I Street
NW, Washington, DC 20001-3710. (202) 777-APHA.
<http://www.apha.org>.
American Veterinary Medical Association (AVMA). 1931
North Meacham Road, Suite 100, Schaumburg, IL
60173-4360. <http://www.avma.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
GALE ENCYCLOPEDIA OF MEDICINE

Cindy L. A. Jones, PhD
Rebecca J. Frey, PhD

Infectious arthritis
Definition
Infectious arthritis, which is sometimes called septic arthritis or pyogenic arthritis, is a serious infection
of the joints characterized by pain, fever, occasional
chills, inflammation and swelling in one or more
joints, and loss of function in the affected joints. It is
considered a medical emergency.

Description
Infectious arthritis can occur in any age group,
including newborns and children. In adults, it usually
affects the wrists or one of the patient’s weightbearing joints–most often the knee–although about
20% of adult patients have symptoms in more than
one joint. Multiple joint infection is common in children
and typically involves the shoulders, knees, and hips.
Some groups of patients are at greater risk for
developing infectious arthritis. These high-risk groups
include:


Patients with chronic rheumatoid arthritis.



Patients with certain systemic infections, including
gonorrhea and HIV infection. Women and male
homosexuals are at greater risk for gonorrheal
arthritis than are male heterosexuals.



Patients with certain types of cancer.



IV drug abusers and alcoholics.



Patients with artificial (prosthetic) joints.



Patients with diabetes, sickle cell anemia, or systemic
lupus erythematosus (SLE).



Patients with recent joint injuries or surgery, or
patients receiving medications injected directly into
a joint.

the bloodstream to the joint. The disease agents may
enter the joint directly from the outside as a result of
an injury or a surgical procedure, or they may be
carried to the joint by the blood from infections elsewhere in the body. The specific organisms vary somewhat according to age group. Newborns are most
likely to acquire gonococcal infections of the joints
from a mother with gonorrhea. Children may also
acquire infectious arthritis from a hospital environment, often as a result of catheter placement. The
organisms involved are usually either Haemophilus
influenzae (in children under two years of age) or
Staphylococcus aureus. In older children or adults,
the infectious organisms include Streptococcus pyogenes and Streptococcus viridans as well as
Staphylococcus aureus. Staphylococcus epidermidis is
usually involved in joint infections related to surgery.
Sexually active teenagers and adults frequently
develop infectious arthritis from Neisseria gonorrhoeae infections. Older adults are often vulnerable
to joint infections caused by gram-negative bacilli,
including Salmonella and Pseudomonas.
Infectious arthritis often has a sudden onset, but
symptoms sometimes develop over a period of three
to 14 days. The symptoms include swelling in the
infected joint and pain when the joint is moved.
Infectious arthritis in the hip may be experienced as
pain in the groin area that becomes much worse if the
patient tries to walk. In 90% of cases, there is some
leakage of tissue fluid into the affected joint. The
joint is sore to the touch; it may or may not be
warm to the touch, depending on how deep the infection lies within the joint. In most cases the patient will
have fever and chills, although the fever may be only
low-grade. Children sometimes develop nausea and
vomiting.
Septic arthritis is considered a medical emergency
because of the damage it causes to bone as well as
cartilage, and its potential for creating septic shock,
which is a potentially fatal condition. Staphylococcus
aureus is capable of destroying cartilage in one or two
days. Destruction of cartilage and bone in turn leads
to dislocations of the joints and bones. If the infection
is caused by bacteria, it can spread to the blood and
surrounding tissues, causing abscesses or even blood
poisoning. The most common complication of infectious arthritis is osteoarthritis.

Diagnosis
Causes and symptoms
In general, infectious arthritis is caused by the
spread of a bacterial, viral, or fungal infection through
GALE ENCYCLOPEDIA OF MEDICINE

The diagnosis of infectious arthritis depends on a
combination of laboratory testing with careful history-taking and physical examination of the affected
2009

Infectious arthritis

National Institute of Allergy and Infectious Diseases
(NIAID). 31 Center Drive, Room 7A50 MSC 2520,
Bethesda, MD, 20892. (301) 496-5717. <http://
www.niaid.nih.gov>.

Infectious arthritis

joint. It is important to keep in mind that infectious
arthritis can coexist with other forms of arthritis,
gout, rheumatic fever, Lyme disease, or other disorders that can cause a combination of joint pain and
fever. In some cases, the doctor may consult a specialist in orthopedics or rheumatology to avoid
misdiagnosis.
Patient history
The patient’s history will tell the doctor whether
he or she belongs to a high-risk group for infectious
arthritis. Sudden onset of joint pain is also important
information.
Physical examination
The doctor will examine the affected joint for
swelling, soreness, warmth, and other signs of infection. Location is sometimes a clue to diagnosis; infection of an unusual joint, such as the joints between the
breastbone and collarbone, or the pelvic joints, often
occurs in drug abusers.
Laboratory tests
Laboratory testing is necessary to confirm the
diagnosis of infectious arthritis. The doctor will perform an arthrocentesis, which is a procedure that
involves withdrawing a sample of synovial fluid (SF)
from the joint with a needle and syringe. SF is a
lubricating fluid secreted by tissues surrounding the
joints. Patients should be warned that arthrocentesis is
a painful procedure. The fluid sample is sent for culture in the sealed syringe. SF from infected joints is
usually streaked with pus or looks cloudy and watery.
Cell counts usually indicate a high level of white cells; a
level higher than 100,000 cells/mm3 or a neutrophil
proportion greater than 90% suggests septic arthritis.
A Gram’s stain of the culture obtained from the SF is
usually positive for the specific disease organism.
Doctors sometimes order a biopsy of the synovial
tissue near the joint if the fluid sample is negative.
Cultures of other body fluids, such as urine, blood,
or cervical mucus, may be taken in addition to the SF
culture.
Diagnostic imaging
Diagnostic imaging is not helpful in the early stages
of infectious arthritis. Destruction of bone or cartilage
does not appear on x rays until 10–14 days after the
onset of symptoms. Imaging studies are sometimes useful if the infection is in a deep-seated joint.
2010

Treatment
Infectious arthritis requires usually requires several days of treatment in a hospital, with follow-up
medication and physical therapy lasting several weeks
or months.
Medications
Because of the possibility of serious damage to the
joint or other complications if treatment is delayed,
the patient will be started on intravenous antibiotics
before the specific organism is identified. After the
disease organism has been identified, the doctor may
give the patient a drug that targets the specific bacterium or virus. Nonsteroidal anti-inflammatory drugs are
usually given for viral infections.
Intravenous antibiotics are given for about two
weeks, or until the inflammation has disappeared. The
patient may then be given a two- to four-week course
of oral antibiotics.
Surgery
In some cases, surgery is necessary to drain fluid
from the infected joint. Patients who need surgical
drainage include those who have not responded to
antibiotic treatment, those with infections of the hip
or other joints that are difficult to reach with arthrocentesis, and those with joint infections related to gunshot or other penetrating wounds.
Patients with severe damage to bone or cartilage
may need reconstructive surgery, but it cannot be performed until the infection is completely gone.
Monitoring and supportive treatment
Infectious arthritis requires careful monitoring
while the patient is in the hospital. The doctor will
drain the joint on a daily basis and remove a small
sample of fluid for culture to check the patient’s
response to the antibiotic.
Infectious arthritis often causes intense pain.
Patients are given medications to relieve pain, together
with hot compresses or ice packs on the affected joint.
In some cases the patient’s arm or leg is put in a splint
to protect the sore joint from accidental movement.
Recovery can be speeded up, however, if the patient
practices range-of-motion exercises to the extent that
the pain allows.

Prognosis
The prognosis depends on prompt treatment
with antibiotics and drainage of the infected
GALE ENCYCLOPEDIA OF MEDICINE

Arthrocentesis—A procedure in which the doctor
inserts a needle into the patient’s joint to withdraw
fluid for diagnostic testing or to drain infected fluid
from the joint.
Pyogenic arthritis—Another name for infectious
arthritis. Pyogenic means that pus is formed during
the disease process.
Sepsis—Invasion of the body by disease organisms
or their toxins. Generalized sepsis can lead to
shock and eventual death.
Septic arthritis—Another name for infectious
arthritis.
Synovial fluid (SF)—A fluid secreted by tissues
surrounding the joints that lubricates the joints.

joint. About 70% of patients will recover without
permanent joint damage. However, many patients
will develop osteoarthritis or deformed joints.
Children with infected hip joints sometimes suffer
damage to the growth plate. If treatment is
delayed, infectious arthritis has a mortality rate
between 5% and 30% due to septic shock and
respiratory failure.

Prevention
Some cases of infectious arthritis are preventable by lifestyle choices. These include avoidance of
self-injected drugs; sexual abstinence or monogamous relationships; and prompt testing and treatment for suspected cases of gonorrhea. Patients
receiving corticosteroid injections into the joints
for osteoarthritis may want to weigh this treatment
method against the increased risk of infectious
arthritis.
Resources
BOOKS

Hellman, David B., ‘‘Arthritis & Musculoskeletal
Disorders.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Infectious hepatitis see Hepatitis A
GALE ENCYCLOPEDIA OF MEDICINE

Infectious mononucleosis
Definition
Infectious mononucleosis is a contagious illness
caused by the Epstein-Barr virus that can affect the
liver, lymph nodes, and oral cavity. While mononucleosis is not usually a serious disease, its primary
symptoms of fatigue and lack of energy can linger for
several months.

Description
Infectious mononucleosis, frequently called
‘‘mono’’ or the ‘‘kissing disease,’’ is caused by the
Epstein-Barr virus (EBV) found in saliva and mucus.
The virus affects a type of white blood cell called the
B lymphocyte producing characteristic atypical lymphocytes that may be useful in the diagnosis of the disease.
While anyone, even young children, can develop
mononucleosis, it occurs most often in young adults
between the ages of 15 and 35 and is especially common in teenagers. The mononucleosis infection rate
among college students who have not previously been
exposed to EBV has been estimated to be about 15%.
In younger children, the illness may not be recognized.
The disease typically runs its course in four to six
weeks in people with normally functioning immune
systems. People with weakened or suppressed immune
systems, such as AIDS patients or those who have
had organ transplants, are particularly vulnerable to
the potentially serious complications of infectious
mononucleosis.

Causes and symptoms
The EBV that causes mononucleosis is related to a
group of herpes viruses, including those that cause
cold sores, chicken pox, and shingles. Most people
are exposed to EBV at some point during their lives.
Mononucleosis is most commonly spread by contact
with virus-infected saliva through coughing, sneezing,
kissing, or sharing drinking glasses or eating utensils.
In addition to general weakness and fatigue,
symptoms of mononucleosis may include any or all
of the following:


Sore throat and/or swollen tonsils



Fever and chills



Nausea and vomiting, or decreased appetite



Swollen lymph nodes in the neck and armpits



Headaches or joint pain
2011

Infectious mononucleosis

KEY TERMS

Infectious mononucleosis



Enlarged spleen



Jaundice



Skin rash.

Complications that can occur with mononucleosis
include a temporarily enlarged spleen or inflamed
liver. In rare instances, the spleen may rupture, producing sharp pain on the left side of the abdomen, a
symptom that warrants immediate medical attention.
Additional symptoms of a ruptured spleen include
light headedness, rapidly beating heart, and difficulty
breathing. Other rare, but potentially life-threatening,
complications may involve the heart or brain. The
infection may also cause significant destruction of
the body’s red blood cells or platelets.
Symptoms do not usually appear until four to
seven weeks after exposure to EBV. An infected
person can be contagious during this incubation time
period and for as many as five months after the
disappearance of symptoms. Also, the virus will be
excreted in the saliva intermittently for the rest of
their lives, although the individual will experience no
symptoms. Contrary to popular belief, the EBV is not
highly contagious. As a result, individuals living in a
household or college dormitory with someone who has
mononucleosis have a very small risk of being infected
unless they have direct contact with the person’s
saliva.

Diagnosis
If symptoms associated with a cold persist longer
than two weeks, mononucleosis is a possibility; however, a variety of other conditions can produce similar
symptoms. If mononucleosis is suspected, a physician
will typically conduct a physical examination, including a ‘‘Monospot’’ antibody blood test that can indicate the presence of proteins or antibodies produced
in response to infection with the EBV. These antibodies may not be detectable, however, until the second
or third weeks of the illness. Occasionally, when this
test is inconclusive, other blood tests may be
conducted.

Treatment
The most effective treatment for infectious mononucleosis is rest and a gradual return to regular
activities. Individuals with mild cases may not require
bed rest but should limit their activities. Any strenuous
activity, athletic endeavors, or heavy lifting should be
avoided until the symptoms completely subside, since
excessive activity may cause the spleen to rupture.
2012

KEY TERMS
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Herpes viruses—A group of viruses that can cause
cold sores, shingles, chicken pox, and congenital
abnormalities. The Epstein-Barr virus which causes
mononucleosis belongs to this group of viruses.
Reye’s syndrome—A very serious, rare disease,
most common in children, which involves an
upper respiratory tract infection followed by brain
and liver damage.

The sore throat and dehydration that usually
accompany mononucleosis may be relieved by drinking water and fruit juices. Gargling salt water or taking
throat lozenges may also relieve discomfort. In addition, taking over-the-counter medications, such as
acetaminophen or ibuprofen, may relieve symptoms,
but aspirin should be avoided because mononucleosis
has been associated with Reye’s syndrome, a serious
illness aggravated by aspirin.
While antibiotics do not affect EBV, the sore
throat accompanying mononucleosis can be complicated by a streptococcal infection, which can be treated with antibiotics. Cortisone anti-inflammatory
medications are also occasionally prescribed for the
treatment of severely swollen tonsils or throat
tissues.

Prognosis
While the severity and length of illness varies,
most people diagnosed with mononucleosis will be
able to return to their normal daily routines within
two to three weeks, particularly if they rest during this
time period. It may take two to three months before a
person’s usual energy levels return. One of the most
common problems in treating mononucleosis, particularly in teenagers, is that people return to their usual
activities too quickly and then experience a relapse of
symptoms. Once the disease has completely run its
course, the person cannot be re-infected.

Prevention
Although there is no way to avoid becoming
infected with EBV, paying general attention to good
hygiene and avoiding sharing beverage glasses or
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

National Institute of Allergy and Infectious Disease.
Building 31, Room 7A-50, 31 Center Drive MSC 2520,
Bethesda, MD 20892-2520. (301) 496-5717.
<http://www.niaid.nih.gov/default.htm>.
OTHER

‘‘Communicable Disease Fact Sheet.’’ New York State
Department of Health.
‘‘Mononucleosis: A Tiresome Disease.’’ Mayo Clinic Online.
<http://www.mayo.ivi.com/mayo/9701/htm/
mono.htm>.

Susan J. Montgomery

Infertility
Definition
Infertility is the failure of a couple to conceive a
pregnancy after trying to do so for at least one full
year. In primary infertility, pregnancy has never
occurred. In secondary infertility, one or both members of the couple have previously conceived, but are
unable to conceive again after a full year of trying.

Description
Currently, in the United States, about 20% of
couples struggle with infertility at any given time.
Infertility has increased as a problem over the last
30 years. Some studies pin the blame for this increase
on social phenomena, including the tendency for marriage to occur at a later age, which means that couples
are trying to start families at a later age. It is well
known that fertility in women decreases with increasing age, as illustrated by the following statistics:


Infertility in married women ages 16–20=4.5%



Infertility in married women ages 35–40=31.8%



Infertility in married women over the age of
40=70%.

Today, individuals often have multiple sexual
partners before they marry and try to have children.
This increase in numbers of sexual partners has led to
an increase in sexually transmitted diseases. Scarring
from these infections, especially from pelvic inflammatory disease (a serious infection of the female
GALE ENCYCLOPEDIA OF MEDICINE

reproductive organs, most commonly caused by
gonorrhea) seems to be in part responsible for the
increase in infertility noted. Furthermore, use of
some forms of a contraceptive called the intrauterine
device (IUD) contributed to an increased rate of pelvic
inflammatory disease, with subsequent scarring.
However, newer IUDs do not lead to this increased
rate of infection.
To understand issues of infertility, it is first necessary to understand the basics of human reproduction.
Fertilization occurs when a sperm from the male
merges with an egg (ovum) from the female, creating
a zygote that contains genetic material (DNA) from
both the father and the mother. If pregnancy is then
established, the zygote will develop into an embryo,
then a fetus, and ultimately a baby will be born.
The male contribution to fertilization and the
establishment of pregnancy is the sperm. Sperm are
small cells that carry the father’s genetic material. This
genetic material is contained within the oval head of
the sperm. The sperm are mixed into a fluid called
semen, which is discharged from the penis during
sexual intercourse. The whip-like tail of the sperm
allows the sperm to swim up the female reproductive
tract, in search of the egg it will try to fertilize.
The female makes many contributions to fertilization and the establishment of pregnancy. The ovum is
the cell that carries the mother’s genetic material.
These ova develop within the ovaries. Once a month,
a single mature ovum is produced, and leaves the
ovary in a process called ovulation. This ovum enters
a tube leading to the uterus (the fallopian tube). The
ovum needs to meet up with the sperm in the fallopian
tube if fertilization is to occur.
When fertilization occurs, the resulting cell
(which now contains genetic material from both the
mother and the father) is called the zygote. This single
cell will divide into multiple other cells within the
fallopian tube, and the resulting cluster of cells
(called a blastocyst) will then move into the womb
(uterus). The uterine lining (endometrium) has been
preparing itself to receive a pregnancy by growing
thicker. If the blastocyst successfully reaches the
inside of the uterus and attaches itself to the wall of
the uterus, then implantation and pregnancy have
been achieved.

Causes and symptoms
Unlike most medical problems, infertility is an
issue requiring the careful evaluation of two separate
individuals, as well as an evaluation of their
2013

Infertility

having close contact with people who have mononucleosis or cold symptoms can help prevent infection.

Infertility

interactions with each other. In about 3–4% of couples, no cause for their infertility will be discovered.
About 40% of the time, the root of the couple’s infertility is due to a problem with the male partner; about
40% of the time, the root of the infertility is due to the
female partner; and about 20% of the time, there are
fertility problems with both the man and the woman.
Recently, a study in Great Britain reported that smoking adds to infertility problems for both men and
women. In addition, men and women who smoke are
less likely to respond to infertility treatment.
The main factors involved in causing infertility,
listing from the most to the least common, include:


Male problems: 35%



Ovulation problems: 20%



Tubal problems: 20%



Endometriosis: 10%



Cervical factors: 5%.
Male factors

Male infertility can be caused by a number of
different characteristics of the sperm. To check for
these characteristics, a sample of semen is obtained
and examined under the microscope (semen analysis).
Four basic characteristics are usually evaluated:


Sperm count refers to the number of sperm present in
a semen sample. The normal number of sperm present in just one milliliter (ml) of semen is more than
20 million. An individual with only 5–20 million
sperm per ml of semen is considered subfertile, an
individual with less than 5 million sperm per ml of
semen is considered infertile.



Sperm are also examined to see how well they swim
(sperm motility) and to be sure that most have normal structure.



Not all sperm within a specimen of semen will be
perfectly normal. Some may be immature, and some
may have abnormalities of the head or tail. A normal
semen sample will contain no more than 25% abnormal forms of sperm.

A microscopic image of a needle (left) injecting sperm cells
directly into a human egg (center). The broad object at right is
a pipette used to hold the ovum steady. (Phototake NYC.
Reproduced by permission.)

Any number of conditions result in abnormal
findings in the semen analysis. Men can be born
with testicles that have not descended properly from
the abdominal cavity (where testicles develop originally) into the scrotal sac, or may be born with only
one instead of the normal two testicles. Testicle size
can be smaller than normal. Past infection (including
mumps) can affect testicular function, as can a past
injury. The presence of abnormally large veins
(varicocele) in the testicles can increase testicular
temperature, which decreases sperm count. History
of having been exposed to various toxins, drug use,
excess alcohol use, use of anabolic steroids, certain
medications, diabetes, thyroid problems, or other
endocrine disturbances can have direct effects on
the formation of sperm (spermatogenesis). Problems
with the male anatomy can cause sperm to be ejaculated not out of the penis, but into the bladder, and
scarring from past infections can interfere with
ejaculation.

Volume of the semen sample is important. An abnormal amount of semen could affect the ability of the
sperm to successfully fertilize an ovum.

Treatment of male infertility includes addressing
known reversible factors first; for example, discontinuing any medication known to have an effect on
spermatogenesis or ejaculation, as well as decreasing
alcohol intake, and treating thyroid or other endocrine disease. Varicoceles can be treated surgically.
Testosterone in low doses can improve sperm motility.

Another test can be performed to evaluate the
ability of the sperm to penetrate the outer coat of the
ovum. This is done by observing whether sperm in a
semen sample can penetrate the outer coat of a guinea
pig ovum; fertilization cannot occur, of course, but
this test is useful in predicting the ability of the individual’s sperm to penetrate a human ovum.

Other treatments of male infertility include
collecting semen samples from multiple ejaculations,
after which the semen is put through a process that
allows the most motile sperm to be sorted out. These
motile sperm are pooled together to create a concentrate that can be deposited into the female partner’s
uterus at a time that coincides with ovulation. In cases



2014

GALE ENCYCLOPEDIA OF MEDICINE

Ovulatory problems
The first step in diagnosing ovulatory problems is
to make sure that an ovum is being produced each
month. A woman’s morning body temperature is
slightly higher around the time of ovulation. A
woman can measure and record her temperatures
daily and a chart can be drawn to show whether or
not ovulation has occurred. Luteinizing hormone
(LH) is released just before ovulation. A simple urine
test can be done to check if LH has been released
around the time that ovulation is expected.
Treatment of ovulatory problems depends on the
cause. If a thyroid or pituitary problem is responsible, simply treating that problem can restore fertility.
(The thyroid and pituitary glands release hormones
that also are involved in regulating a woman’s
menstrual cycle.) Medication can also be used to
stimulate fertility. The most commonly used of
these are called Clomid and Pergonal. These drugs
increase the risk of multiple births (twins, triplets,
etc.). Other possible medications include gonadotropin medications, which are injected medications
made up of hormones produced in the pituitary
glands. They may directly stimulate the ovaries to
produce eggs. Follicle stimulating hormone (FSH)
has a 95% chance of simulating ovulation in women
with an ovulatory problem. However, its use does not
guarantee a successful pregnancy and may lead to
multiple pregnancies.
Pelvic adhesions and endometriosis
Pelvic adhesions and endometriosis can cause
infertility by preventing the sperm from reaching the
egg or interfering with fertilization.

to irritation within the pelvis around the site of this
abnormal tissue and bleeding, and may cause scarring.
Pelvic adhesions cause infertility by blocking the
fallopian tubes. The ovum may be prevented from
traveling down the fallopian tube from the ovary or
the sperm may be prevented from traveling up the
fallopian tube from the uterus.
A hysterosalpingogram (HSG) can show if the
fallopian tubes are blocked. This is an x-ray exam
that tests whether dye material can travel through
the patient’s fallopian tubes. A few women become
pregnant following this x-ray exam. It is thought that
the dye material in some way helps flush out the tubes,
decreasing any existing obstruction. Scarring also can
be diagnosed by examining the pelvic area through the
use of a scope that can be inserted into the abdomen
through a tiny incision made near the naval. This
scoping technique is called laparoscopy.
Pelvic adhesions can be treated during laparoscopy. The adhesions are cut using special instruments.
Endometriosis can be treated with certain medications,
but may also require surgery to repair any obstruction
caused by adhesions.
Cervical factors
The cervix is the opening from the vagina into
the uterus through which the sperm must pass.
Mucus produced by the cervix helps to transport
the sperm into the uterus. Injury to the cervix or
scarring of the cervix after surgery or infection can
result in a smaller than normal cervical opening,
making it difficult for the sperm to enter. Injury or
infection can also decrease the number of glands in
the cervix, leading to a smaller amount of cervical
mucus. In other situations, the mucus produced is the
wrong consistency (perhaps too thick) to allow
sperm to travel through. In addition, some women
produce antibodies (immune cells) that are specifically
directed to identify sperm as foreign invaders and to kill
them.

Pelvic adhesions are fibrous scars. These scars can
be the result of past infections, such as pelvic inflammatory disease, or infections following abortions or
prior births. Previous surgeries can also leave behind
scarring.

Cervical mucus can be examined under a microscope to diagnose whether cervical factors are contributing to infertility. The interaction of a live sperm
sample from the male partner and a sample of cervical
mucus from the female partner can also be examined.
This procedure is called a post-coital test.

Endometriosis may lead to pelvic adhesions.
Endometriosis is the abnormal location of uterine tissue
outside of the uterus. When uterine tissue is planted
elsewhere in the pelvis, it still bleeds on a monthly basis
with the start of the normal menstrual period. This leads

Treatment of cervical factors includes antibiotics
in the case of an infection, steroids to decrease production of anti-sperm antibodies, and artificial insemination techniques to completely bypass the cervical
mucus.

GALE ENCYCLOPEDIA OF MEDICINE

2015

Infertility

where the male partner’s sperm is proven to be absolutely unable to cause pregnancy in the female partner,
and with the consent of both partners, donor sperm
may be used for this process. Depositing the male
partner’s sperm or donor sperm by mechanical
means into the female partner are both forms of
artificial insemination.

Infertility

A

Injection of
sperm and eggs
Fallopian
tube

Ovary

B
Injection of
sperm

Cytoplasm of egg

A. An egg and sperm are injected into the fallopian tube to encourage natural fertilization in a procedure called gamete
intrafallopian transfer (GIFT). B. An alternative to GIFT is the injection of sperm directly into an egg using microscopic needles.
(Illustration by Argosy Inc.)

Treatment
Assisted reproductive techniques include in vitro
fertilization (IVF), gamete intrafallopian transfer
(GIFT), and zygote intrafallopian tube transfer
(ZIFT). These are usually used after other techniques
to treat infertility have failed.
In vitro fertilization involves the use of a drug to
induce the simultaneous release of many eggs from the
female’s ovaries, which are retrieved surgically.
Meanwhile, several semen samples are obtained from
the male partner, and a sperm concentrate is prepared.
The ova and sperm are then combined in a laboratory,
where several of the ova may be fertilized. Cell division
is allowed to take place up to the embryo stage. While
this takes place, the female may be given drugs to
ensure that her uterus is ready to receive an embryo.
Three or four of the embryos are transferred to the
female’s uterus, and the wait begins to see if any or all
of them implant and result in an actual pregnancy.
2016

Success rates of IVF are still rather low. Most
centers report pregnancy rates between 10–20%. Since
most IVF procedures put more than one embryo into
the uterus, the chance for a multiple birth (twins or
more) is greatly increased in couples undergoing IVF.
GIFT involves retrieval of both multiple ova and
semen, and the mechanical placement of both within the
female partner’s fallopian tubes, where one hopes that
fertilization will occur. ZIFT involves the same retrieval
of ova and semen, and fertilization and growth in the
laboratory up to the zygote stage, at which point the
zygotes are placed in the fallopian tubes. Both GIFT and
ZIFT seem to have higher success rates than IVF.

Prognosis
It is very hard to obtain statistics regarding the
prognosis of infertility because many different problems
may exist within and individual or couple trying to conceive. In general, it is believed that of all couples who
GALE ENCYCLOPEDIA OF MEDICINE

Blastocyst—A cluster of cells representing multiple
cell divisions that have occurred in the fallopian tube
after successful fertilization of an ovum by a sperm.
This is the developmental form which must leave the
fallopian tube, enter the uterus, and implant itself in
the uterus to achieve actual pregnancy.
Cervix—The opening from the vagina, which leads
into the uterus.
Embryo—The stage of development of a baby
between the second and eighth weeks after
conception.

‘‘Infertility; Treatment.’’ NWHRC Health Center
March 10, 2004.
Kmietowicz, Zosia. ‘‘Smoking is Causing Impotence,
Miscarriages, and Infertility.’’ British Medical Journal
February 14, 2004: 364.
ORGANIZATIONS

American Society for Reproductive Medicine. 1209
Montgomery Highway, Birmingham, AL 35216-2809.
(205) 978-5000. <http://www.asrm.com>.
International Center for Infertility Information
Dissemination. <http://www.inciid.org>.

Rosalyn Carson-DeWitt, MD
Teresa G. Odle

Endometrium—The lining of the uterus.
Fallopian tube—The tube leading from the ovary
into the uterus. Just as there are two ovaries, there
are two Fallopian tubes.
Fetus—A baby developing in the uterus from the
third month to birth.
Ovary—The female organ in which eggs (ova) are
stored and mature.
Ovum (plural: ova)—The reproductive cell of the
female, which contains genetic information and
participates in the act of fertilization. Also popularly called the egg.
Semen—The fluid that contains sperm, which is
ejaculated by the male.
Sperm—The reproductive cell of the male, which
contains genetic information and participates in the
act of fertilization of an ovum.
Spermatogenesis—The process by which sperm
develop to become mature sperm, capable of
fertilizing an ovum.
Zygote—The result of the sperm successfully fertilizing the ovum. The zygote is a single cell that contains
the genetic material of both the mother and the father.

undergo a complete evaluation of infertility followed by
treatment, about half will ultimately have a successful
pregnancy. Of those couples who do not choose to
undergo evaluation or treatment, about 5% will go on
to conceive after a year or more of infertility.
Resources
BOOKS

Martin, Mary C. ‘‘Infertility.’’ In Current Obstetric and
Gynecologic Diagnosis and Treatment, edited by Alan H.
Cecherney and Martin L. Pernoll. Norwalk, CT: 1994.
GALE ENCYCLOPEDIA OF MEDICINE

Infertility drugs
Definition
Infertility drugs are medicines that help bring
about pregnancy.

Purpose
Infertility is the inability of a man and woman to
achieve pregnancy after at least a year of having
regular sexual intercourse without any type of birth
control. There are many possible reasons for infertility, and finding the most effective treatment for a
couple may involve many tests to find the problem.
For pregnancy to occur, the woman’s reproductive
system must release eggs regularly—a process called
ovulation. The man must produce healthy sperm that
are able to reach and unite with an egg. And once an
egg is fertilized, it must travel to the woman’s uterus
(womb), become implanted and remain there to be
nourished.
If a couple is infertile because the woman is not
ovulating, infertility drugs may be prescribed to stimulate ovulation. The first step usually is to try a drug
such as clomiphene. If that does not work, human
chorionic gonadotropin (HCG) may be tried, usually
in combination with other infertility drugs.
Clomiphene and HCG may also be used to treat
other conditions in both males and females.

Description
Clomiphene (Clomid, Serophene) comes in tablet
form and is available only with a physician’s
2017

Infertility drugs

PERIODICALS

KEY TERMS

Infertility drugs

prescription. Human chorionic gonadotropin is given
as an injection, only under a physician’s supervision.

multiple fetuses can cause problems during pregnancy
and delivery and can even threaten the babies’ survival.

Clomiphene citrate is used to increase the natural
production of the hormones that stimulate ovulation
in otherwise healthy women. When clomiphene is
administered, the body produces higher levels of luteinizing hormone (LH), follicle stimulating hormone
(FSH), and gonadotropins. These hormones induce
ovulation.

Having intercourse at the proper time in the
woman’s menstrual cycle helps increase the chance of
pregnancy. The physician may recommend using an
ovulation prediction test kit to help determine the best
times for intercourse.

Human chorionic gonadotropin (hCG) is sold
under many brand names including Gonic, Pregnyl
and Profasi. This hormone stimulates the gonads in
both men and women. In men, hCG increases androgen production. In women, it increases the levels of
progesterone. Human chorionic gonadotropin can
help stimulate ovulation in women.
Although some people believe that hCG can help
lose weight, there is no evidence that this hormone
offers any benefit in weight loss programs. It should
not be used for this purpose.
A number of other natural and synthetic hormones are used to induce ovulation. Urofollitropins
(Fertinex) is a concentrated preparation of human
hormones, while follitropin alfa (Gonal-F) and follitropin beta (Follistim) are human FSH preparations
of recombinant DNA origin. Developments in this
field are continuous. For example, in June 2004, the
U.S. Food and Drug Administration (FDA) approved
a follitropin beta injection in individualized doses for
women to self-inject.
Menotropins (Pergonal, Humegon, Repronex) are
given with human chorionic gonadotropin to stimulate
ovulation in women and sperm production in men.

Recommended dosage
The dosage may be different for different patients.
The physician who prescribed the drug or the pharmacist who filled the prescription will recommend the
correct dosage.
Clomiphene must be taken at certain times during
the menstrual cycle and patients should follow directions exactly.

Precautions
Seeing a physician regularly while taking infertility drugs is important.
Treatment with infertility drugs increases the
chance of multiple births. Although this may seem like
a good thing to couples who want children very badly,
2018

Some people feel dizzy or lightheaded, or less alert
when using clomiphene. The medicine may also cause
blurred vision and other vision changes. Anyone who
takes clomiphene should not drive, use machines or do
anything else that might be dangerous until they have
found out how the drugs affect them.
Questions remain about the safety of long-term
treatment with clomiphene. Women should not have
more than six courses of treatment with this drug and
should ask their physicians for the most up-to-date
information about its use.
Special conditions
People who have certain medical conditions or
who are taking certain other medicines may have problems if they take infertility drugs. Before taking these
drugs, patients should tell the physician about any of
these conditions:
ALLERGIES. Anyone who has had unusual reactions to infertility drugs in the past should let his or
her physician know before taking the drugs again. The
physician should also be told about any allergies to
foods, dyes, preservatives, or other substances.
PREGNANCY. Clomiphene may cause birth defects
if taken during pregnancy. Women who think they
have become pregnant while taking clomiphene
should stop taking the medicine immediately and
check with their physicians.
OTHER MEDICAL CONDITIONS. Infertility drugs
may make some medical conditions worse. Before
using infertility drugs, people with any of these medical problems should make sure their physicians are
aware of their conditions:


Endometriosis



Fibroid tumors of the uterus



Unusual vaginal bleeding



Ovarian cyst



Enlarged ovaries



Inflamed veins caused by blood clots



Liver disease, now or in the past



Depression.
GALE ENCYCLOPEDIA OF MEDICINE

Endometriosis—A condition in which tissue like
that normally found in the lining of the uterus is
present outside the uterus. The condition often
causes pain and bleeding.
Fetus—A developing baby inside the womb.
Fibroid tumor—A noncancerous tumor formed of
fibrous tissue.
Ovary—A reproductive organ in females that
produces eggs and hormones.

Infertility therapies
Definition
Infertility is the inability of a man and a woman to
conceive a child through sexual intercourse. There are
many possible reasons for the problem, which can
involve the man, the woman, or both partners.
Various treatments are available that enable a
woman to become pregnant; the correct one will
depend on the specific cause of the infertility.

Purpose
USE OF CERTAIN MEDICINES. Taking infertility
drugs with certain other medicines may affect the way
the drugs work or may increase the chance of side effects.

Side effects
When used in low doses for a short time, clomiphene
and HCG rarely cause side effects. However, anyone
who has stomach or pelvic pain or bloating while taking
either medicine should check with a physician immediately. Infertility drugs may also cause less serious symptoms such as hot flashes, breast tenderness or swelling,
heavy menstrual periods, bleeding between menstrual
periods, nausea or vomiting, dizziness, lightheadedness,
irritability, nervousness, restlessness, headache, tiredness, sleep problems, or depression. These problems
usually go away as the body adjusts to the drug and do
not require medical treatment unless they continue or
they interfere with normal activities.
Other side effects are possible. Anyone who has
unusual symptoms after taking infertility drugs should
get in touch with a physician.

Interactions
Infertility drugs may interact with other medicines.
When this happens, the effects of one or both of the
drugs may change or the risk of side effects may be
greater. Anyone who takes infertility drugs should let
the physician know all other medicines she is taking.
Resources

Infertility treatment is aimed at enabling a woman
to have a baby by treating the man, the woman, or both
partners. During normal conception of a child, the man’s
sperm will travel to the woman’s fallopian tubes, where,
if conditions are right, it will encounter an egg that has
been released from the ovary. The sperm will fertilize the
egg, which will enter the uterus where it implants and
begins to divide, forming an embryo. The embryo will
develop during pregnancy into a baby.
Infertility treatment attempts to correct or compensate for any abnormalities in this process that
prevent the fertilization of an egg or development of
an embryo.

Precautions
It is important for a couple contemplating infertility
treatment to examine their own ideas and feelings about
the process and consider ethical objections before the
woman becomes pregnant from such treatment.

Description
About 90% of women who are trying to get
pregnant and use no birth control will do so within one
year. If, after one year of having frequent sexual intercourse with no contraception a couple has not conceived,
they should seek the advice of a physician. Tests can be
performed to look for possible infertility problems.
Treating an underlying infection or illness is
the first step in infertility treatment. The physician
may also suggest improving general health, dietary
changes, reducing stress, and counseling.

PERIODICALS

Georgi, Kristen. ‘‘News from the FDA.’’ Patient Care June
2004: 10.

Nancy Ross-Flanigan
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Low sperm count treatments
The most common cause of male infertility is
failure to produce enough healthy sperm. For
2019

Infertility therapies

KEY TERMS

Infertility therapies

fertilization to happen, the number of sperm cells in
the man’s semen (the fluid ejected during sexual intercourse) must be sufficient, and the sperm cells must
have the right shape, appearance, and activity
(motility).
Defects in the sperm can be caused by an infection
resulting from a sexually transmitted disease, a blockage caused by a varicose vein in the scrotum (varicocele), an endocrine imbalance, or problems with other
male reproductive organs (such as the testicles,
prostate gland, or seminal vesicles).
If a low sperm count is the problem, it is possible
to restore fertility by:


Treating underlying infections.



Timing sex to coincide with the time the woman is
ovulating, which means that the egg is released from
the ovary and is beginning to travel down the fallopian tube (the site of fertilization).



Having sex less often to build up the number of
sperm in the semen.



Treating any endocrine imbalance with drugs.



Having a surgical procedure to remove a varicocele
(varicocelectomy).
Fertility drugs

If infertility is due to a woman’s failure to release
eggs from the ovary (ovulate), fertility drugs can help
bring hormone levels into balance, stimulating the
ovaries and triggering egg production.
Surgical repair
In some women, infertility is due to blocked
fallopian tubes. The egg is released from the ovary,
but the sperm is prevented from reaching it because
of a physical obstruction in the fallopian tube. If
this is the case, surgery may help repair the damage.
Microsurgery can sometimes repair the damage to
scarred fallopian tubes if it is not too severe. Not all
tube damage can be repaired, however, and most tubal
problems are more successfully treated with in vitro
fertilization.
Fibroid tumors in the uterus also may cause
infertility, and they can be surgically treated.
Endometriosis, a condition in which parts of the lining
of the uterus become imbedded on other internal
organs (such as the ovaries or fallopian tubes) may
contribute to infertility. It may be necessary to surgically remove the endometrial tissue to improve
fertility.
2020

Artificial insemination
Artificial insemination may be tried if sperm
count is low, the man is impotent, or the woman’s
vagina creates a hostile environment for the sperm.
The procedure is not always successful. In this procedure, the semen is collected and placed into the
woman’s cervix with a small syringe at the time of
ovulation. From the cervix, it can travel to the
fallopian tube where fertilization takes place. If the
partner’s sperm count is low, it can be mixed with
donor sperm before being transferred into the uterus.
If there is no sperm in the male partner’s semen,
then artificial insemination can be performed using a
donor’s sperm obtained from a sperm bank.
Assisted reproductive technologies
Some fertility treatments require removal of the
eggs and/or sperm and manipulation of them in certain
ways in a laboratory to assist fertilization. These techniques are called assisted reproductive technologies.
IN VITRO FERTILIZATION (IVF). When infertility
cannot be treated by other means or when the cause
is not known, it is still possible to become pregnant
through in vitro fertilization (IVF), a costly, complex
procedure that achieves pregnancy 20% of the time.

In this procedure, a woman’s eggs are removed by
withdrawing them with a special needle. Attempts are
then made to fertilize the eggs with sperm from her
partner or a donor. This fertilization takes place in a
petri dish in a laboratory. The fertilized egg (embryo)
is then returned to the woman’s uterus.
Often, three to six fertilized eggs are returned at
the same time into the uterus. Usually one or two of
the embryos survive and grow into fetuses, but sometimes three or more fetuses result.
A child born in this method is popularly known as
a ‘‘test tube baby,’’ but in fact the child actually develops inside the mother. Only the fertilization of the egg
takes place in the laboratory.
INTRACYTOPLASMIC SPERM INJECTION (ICSI). In a
variation of IVF called intracytoplasmic sperm injection (ICSI), single sperm cells are injected directly into
each egg. This may be helpful for men with severe
infertility.
GAMETE INTERFALLOPIAN TRANSFER (GIFT). In this
technique, sperm and eggs are placed directly into
the woman’s fallopian tubes to encourage fertilization to occur naturally. This procedure is done with
the help of laparoscopy. In laparoscopy, a small tube
with a viewing lens at one end is inserted into the

GALE ENCYCLOPEDIA OF MEDICINE

Gamete—An egg (ovum) from the female or a
mature sperm from the male.
Laparoscopy—A procedure in which a viewing
tube is inserted through the abdominal wall to
examine a woman’s reproductive organs.
Ovulation—The release of an egg from the ovary.
Fertilization can occur within a day or two of
ovulation.
Zygote—A fertilized egg.

Typically, at least half of all couples who are
infertile will respond to treatment with a successful
pregnancy. For those who cannot become pregnant
with treatment or insemination, surrogate parenting
or adopting may be a workable option.
Resources
ORGANIZATIONS

American Society for Reproductive Medicine. 1209
Montgomery Highway, Birmingham, AL 35216.
(205) 978-5000.
Resolve. 1310 Broadway, Somerville, MA 02144-1731.
(617) 623-0744. <http://www.resolve.org>.

abdomen through a small incision. The lens allows
the physician to see inside the patient on a video
monitor.
ZYGOTE INTRAFALLOPIAN TRANSFER (ZIFT). If infertility is caused by a low sperm count, zygote intrafallopian transfer (ZIFT) can be tried. This technique
combines GIFT and IVF. This procedure is also called
a ‘‘tubal embryo transfer.’’

In this technique, in-vitro fertilization is first performed, so that the actual fertilization takes place and
is confirmed in the laboratory. Two days later, instead
of placing the embryo in the uterus, the physician
performs laparoscopy to place the embryos in the
fallopian tube, much like the GIFT procedure.
A woman must have at least one functioning
fallopian tube in order to participate in ZIFT.

Preparation
Couples who are having fertility problems may
want to limit or avoid:


Tobacco



Alcohol



Caffeine



Stress



Tight-fitting undershorts (men)



Hot tubs, saunas and steam rooms (high temperatures can kill sperm).

Risks
Women who take fertility drugs have a higher
likelihood of getting pregnant with more than one
child at once. There are also rare but serious side
effects to fertility drugs.
GALE ENCYCLOPEDIA OF MEDICINE

Carol A. Turkington

Influenza
Definition
Usually referred to as the flu or grippe, influenza
is a highly infectious respiratory disease. The disease is
caused by certain strains of the influenza virus. When
the virus is inhaled, it attacks cells in the upper respiratory tract, causing typical flu symptoms such as
fatigue, fever and chills, a hacking cough, and body
aches. Influenza victims are also susceptible to potentially life-threatening secondary infections. Although
the stomach or intestinal ‘‘flu’’ is commonly blamed
for stomach upsets and diarrhea, the influenza virus
rarely causes gastrointestinal symptoms. Such symptoms are most likely due to other organisms such as
rotavirus, Salmonella, Shigella, or Escherichia coli.

Description
The flu is considerably more debilitating than the
common cold. Influenza outbreaks occur suddenly,
and infection spreads rapidly. The annual death toll
attributable to influenza and its complications
averages 20,000 in the United States alone. In the
1918-1919 Spanish flu pandemic, the death toll
reached a staggering 20–40 million worldwide.
Approximately 500,000 of these fatalities occurred in
America.
Influenza outbreaks occur on a regular basis. The
most serious outbreaks are pandemics, which affect
millions of people worldwide and last for several
months. The 1918–1919 influenza outbreak serves as
2021

Influenza

Normal results

KEY TERMS

Influenza

the primary example of an influenza pandemic.
Pandemics also occurred in 1957 and 1968 with the
Asian flu and Hong Kong flu, respectively. The Asian
flu was responsible for 70,000 deaths in the United
States, while the Hong Kong flu killed 34,000.
Epidemics are widespread regional outbreaks that
occur every two to three years and affect 5–10% of the
population. The Russian flu in the winter of 1977 is an
example of an epidemic. A regional epidemic is shorter
lived than a pandemic, lasting only several weeks.
Finally, there are smaller outbreaks each winter that
are confined to specific locales.
The earliest existing descriptions of influenza were
written nearly 2500 years ago by the ancient Greek
physician Hippocrates. Historically, influenza was
ascribed to a number of different agents, including
‘‘bad air’’ and several different bacteria. In fact, its
name comes from the Italian word for ‘‘influence,’’
because people in eighteenth-century Europe thought
that the disease was caused by the influence of bad
weather. It was not until 1933 that the causative agent
was identified as a virus.
There are three types of influenza viruses, identified as A, B, and C. Influenza A can infect a range of
animal species, including humans, pigs, horses, and
birds, but only humans are infected by types B and
C. Influenza A is responsible for most flu cases, while
infection with types B and C virus are less common
and cause a milder illness.
In the United States, 90% of all deaths from
influenza occur among persons older than 65.
Flu-related deaths have increased substantially in the
United States since the 1970s, largely because of the
aging of the American population. In addition, elderly
persons are vulnerable because they are often reluctant
to be vaccinated against flu.
A new concern regarding influenza is the possibility
that hostile groups or governments could use the virus
as an agent of bioterrorism. A report published in early
2003 noted that Type A influenza virus has a high
potential for use as such an agent because of the virulence of the Type A strain that broke out in Hong Kong
in 1997 and the development of laboratory methods for
generating large quantities of the virus. The report
recommended the stockpiling of present antiviral
drugs and speeding up the development of new ones.

Causes and symptoms
Approximately one to four days after infection
with the influenza virus, the victim is hit with an
array of symptoms. ‘‘Hit’’ is an appropriate term,
2022

because symptoms are sudden, harsh, and unmistakable. Typical influenza symptoms include the abrupt
onset of a headache, dry cough, and chills, rapidly
followed by overall achiness and a fever that may run
as high as 1048F (408C). As the fever subsides, nasal
congestion and a sore throat become noticeable. Flu
victims feel extremely tired and weak and may not
return to their normal energy levels for several days
or even a couple of weeks.
Influenza complications usually arise from bacterial infections of the lower respiratory tract. Signs of a
secondary respiratory infection often appear just as
the victim seems to be recovering. These signs include
high fever, intense chills, chest pains associated with
breathing, and a productive cough with thick yellowish green sputum. If these symptoms appear, medical
treatment is necessary. Other secondary infections,
such as sinus or ear infections, may also require medical intervention. Heart and lung problems, and other
chronic diseases, can be aggravated by influenza,
which is a particular concern with elderly patients.
With children and teenagers, it is advisable to be
alert for symptoms of Reye’s syndrome, a rare, but
serious complication. Symptoms of Reye’s syndrome
are nausea and vomiting, and more seriously, neurological problems such as confusion or delirium. The
syndrome has been associated with the use of aspirin
to relieve flu symptoms.

Diagnosis
Although there are specific tests to identify the
flu virus strain from respiratory samples, doctors typically rely on a set of symptoms and the presence of
influenza in the community for diagnosis. Specific
tests are useful to determine the type of flu in the
community, but they do little for individual treatment.
Doctors may administer tests, such as throat cultures,
to identify secondary infections.
Since 1999, however, seven rapid diagnostic tests
for flu have become commercially available. These
tests appear to be especially useful in diagnosing flu
in children, allowing doctors to make more accurate
treatment decisions in less time.

Treatment
Essentially, a bout of influenza must be allowed to
run its course. Symptoms can be relieved with bed rest
and by keeping well hydrated. A steam vaporizer may
make breathing easier, and pain relievers will take
care of the aches and pain. Food may not seem very
appetizing, but an effort should be made to consume
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatments
There are several alternative treatments that may
help in fighting off the virus and recovering from the
flu, in addition to easing flu symptoms.
A transmission electron microscopy (TEM) image of
influenza viruses budding from the surface of an infected
cell. (Photo Researchers, Inc. Reproduced by permission.)



Acupuncture and acupressure. Both are said to stimulate natural resistance, relieve nasal congestion and
headaches, fight fever, and calm coughs, depending
on the acupuncture and acupressure points used.

nourishing food. Recovery should not be pushed too
rapidly. Returning to normal activities too quickly
invites a possible relapse or complications.



Aromatherapy. Aromatherapists recommend gargling daily with one drop each of the essential oils
of tea tree (Melaleuca spp.) and lemon mixed in a
glass of warm water. If already suffering from the flu,
two drops of tea tree oil in a hot bath may help
ease the symptoms. Essential oils of eucalyptus
(Eucalyptus globulus) or peppermint (Mentha piperita) added to a steam vaporizer may help clear chest
and nasal congestion.



Herbal remedies. Herbal remedies can be used stimulate the immune system (echinacea), as antivirals
(Hydrastis canadensis) goldenseal and garlic (Allium
sativum), or directed at whatever symptoms arise as a
result of the flu. For example, an infusion of boneset
(Eupatroium perfoliatum) may counteract aches and
fever, and yarrow (Achillea millefolium) or elderflower tinctures may combat chills.



Homeopathy. To prevent flu, a homeopathic remedy
called Oscillococcinum may be taken at the first sign
of flu symptoms and repeated for a day or two.
Although oscillococcinum is a popular flu remedy
in Europe, however, a research study published in
2003 found it to be ineffective. Other homeopathic
remedies recommended vary according to the specific flu symptoms present. Gelsemium (Gelsemium
sempervirens) is recommended to combat weakness
accompanied by chills, a headache, and nasal congestion. Bryonia (Bryonia alba) may be used to treat
muscle aches, headaches, and a dry cough. For restlessness, chills, hoarseness, and achy joints, poison
ivy (Rhus toxicodendron) is recommended. Finally,
for achiness and a dry cough or chills, Eupatorium
perfoliatum is suggested.



Hydrotherapy. A bath to induce a fever will speed
recovery from the flu by creating an environment in

Drugs
Since influenza is a viral infection, antibiotics
are useless in treating it. However, antibiotics are
frequently used to treat secondary infections.
Over-the-counter medications are used to treat
flu symptoms, but it is not necessary to purchase a
medication marketed specifically for flu symptoms.
Any medication that is designed to relieve symptoms,
such as pain and coughing, will provide some relief.
Medications containing alcohol, however, should be
avoided because of the dehydrating effects of alcohol.
The best medicine for symptoms is simply an analgesic, such as aspirin, acetaminophen, or naproxen.
Without a doctor’s approval, aspirin is generally
not recommended for people under 18 owing to its
association with Reye’s syndrome, a rare aspirinassociated complication seen in children recovering
from the flu. To be on the safe side, children should
receive acetaminophen or ibuprofen to treat their
symptoms.
There are four antiviral drugs marketed for treating
influenza as of 2003. To be effective, treatment should
begin no later than two days after symptoms appear.
Antivirals may be useful in treating patients who have
weakened immune systems or who are at risk for developing serious complications. They include amantadine
(Symmetrel, Symadine) and rimantadine (Flumandine),
which work against Type A influenza, and zanamavir
(Relenza) and oseltamavir phosphate (Tamiflu),
which work against both Types A and B influenza.
Amantadine and rimantadine can cause side effects
GALE ENCYCLOPEDIA OF MEDICINE

2023

Influenza

such as nervousness, anxiety, lightheadedness, and
nausea. Severe side effects include seizures, delirium,
and hallucination, but are rare and are nearly always
limited to people who have kidney problems, seizure
disorders, or psychiatric disorders. The new drugs
zanamavir and oseltamavir phosphate have few side
effects but can cause dizziness, jitters, and insomnia.

Influenza

the body where the flu virus cannot survive. The
patient should take a bath as hot as he/she can
tolerate and remain in the bath for 20–30 minutes.
While in the bath, the patient drinks a cup of yarrow
or elderflower tea to induce sweating. During the
bath, a cold cloth is held on the forehead or at the
nape of the neck to keep the temperature down in
the brain. The patient is assisted when getting out of
the bath (he/she may feel weak or dizzy) and then
gets into bed and covers up with layers of blankets
to induce more sweating.




Traditional Chinese medicine (TCM). Practitioners
of TCM recommend mixtures of herbs to prevent flu
as well as to relieve symptoms once a person has
fallen ill. There are several different recipes for these
remedies, but most contain ginger and Japanese
honeysuckle in addition to other ingredients.
Vitamins. For adults, 2–3 grams of vitamin C daily
may help prevent the flu. Increasing the dose to 5–7
grams per day during the flu can felp fight the infection.
(The dose should be reduced if diarrhea develops.)

Prognosis
Following proper treatment guidelines, healthy
people under the age of 65 usually suffer no long-term
consequences associated with flu infection. The elderly
and the chronically ill are at greater risk for secondary
infection and other complications, but they can also
enjoy a complete recovery.
Most people recover fully from an influenza infection, but it should not be viewed complacently.
Influenza is a serious disease, and approximately 1 in
1,000 cases proves fatal.

Prevention
The Centers for Disease Control and Prevention
recommend that people get an influenza vaccine
injection each year before flu season starts. In the
United States, flu season typically runs from late
December to early March. Vaccines should be
received two to six weeks prior to the onset of flu
season to allow the body enough time to establish
immunity. Adults only need one dose of the yearly
vaccine, but children under nine years of age who
have not previously been immunized should receive
two doses with a month between each dose.
Each season’s flu vaccine contains three virus
strains that are the most likely to be encountered in
the coming flu season. When there is a good match
between the anticipated flu strains and the strains
used in the vaccine, the vaccine is 70–90% effective in
2024

people under 65. Because immune response diminishes
somewhat with age, people over 65 may not receive the
same level of protection from the vaccine, but even if
they do contract the flu, the vaccine diminishes the
severity and helps prevent complications.
The virus strains used to make the vaccine are
inactivated and will not cause the flu. In the past, flu
symptoms were associated with vaccine preparations
that were not as highly purified as modern vaccines,
not to the virus itself. In 1976, there was a slightly
increased risk of developing Guillain-Barré syndrome,
a very rare disorder, associated with the swine flu
vaccine. This association occurred only with the 1976
swine flu vaccine preparation and has never recurred.
Serious side effects with modern vaccines are
extremely unusual. Some people experience a slight
soreness at the point of injection, which resolves
within a day or two. People who have never been
exposed to influenza, particularly children, may
experience one to two days of a slight fever, tiredness,
and muscle aches. These symptoms start within 6–12
hours after the vaccination.
It should be noted that certain people should not
receive an influenza vaccine. Infants six months and
younger have immature immune systems and will not
benefit from the vaccine. Since the vaccines are prepared using hen eggs, people who have severe allergies
to eggs or other vaccine components should not
receive the influenza vaccine. As an alternative, they
may receive a course of amantadine or rimantadine,
which are also used as a protective measure against
influenza. Other people who might receive these drugs
are those that have been immunized after the flu season has started or who are immunocompromised, such
as people with advanced HIV disease. Amantadine
and rimantadine are 70–90% effective in preventing
influenza.
Certain groups are strongly advised to be vaccinated because they are at increased risk for influenzarelated complications:


All people 65 years and older



Residents of nursing homes and chronic-care
facilities, regardless of age



Adults and children who have chronic heart or lung
problems, such as asthma



Adults and children who have chronic metabolic
diseases, such as diabetes and renal dysfunction, as
well as severe anemia or inherited hemoglobin
disorders



Children and teenagers who are on long-term aspirin
therapy
GALE ENCYCLOPEDIA OF MEDICINE

Bioterrorism—The intentional use of diseasecausing microbes or other biologic agents to
intimidate or terrorize a civilian population for
political or military reasons. Type A influenza
virus could be used as an agent of bioterrorism.
Common cold—A mild illness caused by a upper
respiratory viruses. Usual symptoms include nasal
congestion, coughing, sneezing, throat irritation,
and a low-grade fever.
Epidemic—A widespread regional disease outbreak.
Guillain-Barré syndrome—Also called acute idiopathic polyneuritis, this condition is a neurologic
syndrome that can cause numbness in the limbs and
muscle weakness following certain viral infections.
Pandemic—Worldwide outbreak of an infection,
afflicting millions of victims.



Women who will be in their second or third trimester
during flu season or women who are nursing



Anyone who is immunocompromised, including
HIV-infected persons, cancer patients, organ transplant recipients, and patients receiving steroids,
chemotherapy, or radiation therapy



Anyone in contact with the above groups, such as
teachers, care givers, health-care personnel, and
family members



Travelers to foreign countries.

A person need not be in one of the at-risk categories listed above, however, to receive a flu vaccination. Anyone who wants to forego the discomfort and
inconvenience of an influenza attack may receive the
vaccine.
As of early 2003, researchers are working on
developing an intranasal flu vaccine in aerosol form.
An aerosol vaccine using a weakened form of Type A
influenza virus has been tested in pilot studies and
awaits further clinical trials.

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II. ‘‘CAM Therapies for Specific Conditions:
Colds/Flu.’’ New York: Simon & Schuster, 2002.
PERIODICALS

Elkins, Rita. ‘‘Combat Colds and Flu.’’ Let’s Live.
68 (January 2000): 81+.
Jonas, W. B., T. J. Kaptchuk, and K. Linde. ‘‘A Critical
Overview of Homeopathy.’’ Annals of Internal Medicine
138 (March 4, 2003): 393–399.
Krug, R. M. ‘‘The Potential Use of Influenza Virus as an
Agent for Bioterrorism.’’ Antiviral Research 57
(January 2003): 147–150.
Oxford, J. S., S. Bossuyt, S. Balasingam, et al. ‘‘Treatment of
Epidemic and Pandemic Influenza with Neuraminidase
and M2 Proton Channel Inhibitors.’’ Clinical
Microbiology and Infection 9 (January 2003): 1–14.
Roth, Y., J. S. Chapnik, and P. Cole. ‘‘ Feasibility of Aerosol
Vaccination in Humans.’’ Annals of Otology,
Rhinology, and Laryngology 112 (March 2003):
264–270.
Shortridge, K. F., J. S. Peiris, and Y. Guan. ‘‘The Next
Influenza Pandemic: Lessons from Hong Kong.’’
Journal of Applied Microbiology 94, Supplement
(2003): 70S–79S.
Storch, G. A. ‘‘Rapid Diagnostic Tests for Influenza.’’
Current Opinion in Pediatrics 15 (February 2003):
77–84.
Thompson, W. W., D. K. Shay, E. Weintraub, et al.
‘‘Mortality Associated with Influenza and Respiratory
Syncytial Virus in the United States.’’ Journal of the
American Medical Association 289 (January 8, 2003):
179–186.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
National Institute of Allergy and Infectious Diseases
(NIAID). 31 Center Drive, MSC 2520, Bethesda, MD
20892-2520. <http://www.niaid.nih.gov>.
OTHER

NIAID Fact Sheet: Flu. Bethesda, MD: NIAID, January
2003. <http://www.niaid.nih.gov/factsheets/flu.htm>.

Julia Barrett
Rebecca J. Frey, PhD

Infrequent menstruation see Oligomenorrhea

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Respiratory Viral Diseases: Influenza.’’ Section 13,
Chapter 162. In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

GALE ENCYCLOPEDIA OF MEDICINE

Inhalation therapies
Definition
Inhalation therapies are a group of respiratory, or
breathing, treatments designed to help restore or
2025

Inhalation therapies

KEY TERMS

Inhalation therapies

improve breathing function in patients with a variety
of diseases, conditions, or injuries. The treatments
range from at-home oxygen therapy for patients with
chronic obstructive pulmonary disease to mechanical
ventilation for patients with acute respiratory failure.
Inhalation therapies usually include the following
categories:


Oxygen therapy



Incentive spirometry



Continuous positive airway pressure (CPAP)



Oxygen chamber therapy



Mechanical ventilation



Newborn life support.

Purpose
Inhalation therapies are ordered for various
stages of diseases which are causing progressive or
sudden respiratory failure. Although physicians
generally follow guidelines to assign specific therapy
according the type and stage of a disease, the ultimate
decision is based on a number of tests indicating pulmonary function and the presence or absence of oxygen in body organs and tissues.
Oxygen therapy
Oxygen therapy is most commonly ordered to
support patients with emphysema and other chronic
obstructive pulmonary disease (COPD). The oxygen
therapy is usually ordered once decreased oxygen
saturation in the blood or tissues is demonstrated.
Oxygen therapy may also be used in the hospital
setting to help return a patient’s breathing and oxygen
levels to normal.
Incentive spirometry
Spirometry is a diagnostic method for measuring
gases and respiratory function. Incentive spirometry
may be ordered to help patients practice and improve
controlled breathing. It may be ordered after surgery
to the abdomen, lungs, neck, or head.
Continuous positive airway pressure (CPAP)
Common uses of continuous positive airway
pressure include sleep apnea, respiratory distress
syndrome in infants, and adult respiratory distress
syndrome. Signs of atelectasis (absence of gas from
the lungs) or abnormalities of the lower airways may
also indicate CPAP.
2026

Oxygen chamber therapy
Oxygen chamber therapy is ordered for various
causes that indicate immediate need for oxygen
saturation in the blood. Divers with decompression
illness, climbers in high altitude, patients suffering
from severe carbon dioxide poisoning, and children
or adults in acute respiratory distress may require
oxygen chamber therapy. In recent years, physicians
have also used the forced pressure of oxygen chambers
to help heal burns and other wounds, since the pressure
under which the oxygen is delivered can reach areas
that are blocked off or suffering from poor circulation.
Mechanical ventilation
Mechanical ventilation is ordered for patients in
acute respiratory distress, and is often used in an intensive care situation. In some cases, mechanical ventilation is a final attempt to continue the breathing function
in a patient and may be considered ‘‘life-sustaining.’’
Newborn life support
Newborn babies, particularly those who were premature, may require inhalation therapies immediately
upon birth, since the lungs are among the last organs
to fully develop. Some newborns suffer from serious
respiratory problems or birth complications, such as
respiratory distress syndrome, neonatal wet lung syndrome, apnea of prematurity or persistent fetal circulation, which may require inhalation therapies.

Precautions
There are numerous indications for not prescribing various inhalation therapies.
Oxygen therapy
Patients and family members who smoke should
not have oxygen prescribed or should avoid smoking
in the area to prevent combustion. Sedatives should be
avoided for patients on oxygen therapy.
Incentive spirometry
Patients who are unable or unwilling to properly
and consistently practice incentive spirometry as prescribed should not receive this form of treatment.
Continuous positive airway pressure (CPAP)
Patients unable or unwilling to comply with the
physician’s instructions for use of CPAP are not likely
to have it prescribed. Extremely obese patients may
GALE ENCYCLOPEDIA OF MEDICINE

Oxygen chamber therapy
Complications may arise from this form of treatment and during transport to or from the oxygen
chamber. Therefore, some patients may not receive
enough benefit to outweigh possible complications.
All patients, particularly children, must be carefully
monitored.
Mechanical ventilation
Use of mechanical ventilation will be carefully
weighed against benefit and possible risks. Some
patients will require sedation to prevent fighting of
the ventilator, which can increase the risk of
complications.
Newborn life support
Not all infants with breathing problems will
require measures as severe as mechanical ventilation.
The physician will make the determination based on
weight and condition of the infant. Newborns with
patent ductus arteriosis, a handicap affecting the pulmonary artery, are more likely to suffer pulmonary
hemorrhage from mechanical ventilation.

are ambulatory, especially those who work, will need a
system with a small portable tank. Depending on the
system chosen, frequent deliveries of oxygen and filling of portable tanks will be necessary.
In the case of respiratory distress in newborns or
adults, oxygen therapy may be attempted before
mechanical ventilation since it is a noninvasive and
less expensive choice. Oxygen has been found effective
in treating patients with other diseases such as cystic
fibrosis, chronic congestive heart failure, or other lung
diseases.
Incentive spirometry
Incentive spirometry is also referred to as sustained maximal inspiration. It is designed to mimic
natural sighs and yawns. A device provides positive
feedback when a patient inhales at a predetermined
rate and sustains the breath for a specific period of
time. This helps teach the patient to take long, slow,
and deep breaths. A spirometer, or equipment that
measures pulmonary function, is provided to the
patient and a respiratory therapist will work with the
patient to demonstrate and explain the technique.
Once patients show mastery of the technique, they
are instructed to practice the exercises frequently on
their own.
Continuous positive airway pressure (CPAP)

Description
Oxygen therapy
Once a patient shows hypoxemia, or decreased
oxygen in arterial blood, supplemental oxygen may
be ordered. The main purpose of the oxygen is to
prevent damage to vital organs resulting from inadequate oxygen supply. The lowest possible saturation
will be given to keep the patient’s measurements at a
minimum acceptable level. The oxygen is administered
through a mask or nasal tube, or sometimes directly
into the trachea. The amount of oxygen prescribed is
measured in liters of flow per minute. Patients with
chronic hypoxemia, most likely in late stages of
COPD, will often receive long-term oxygen therapy.
Most patients will receive their long-term oxygen
therapy through home oxygen use. A physician must
prescribe home oxygen and levels will be monitored to
ensure that the correct amount of oxygen is administered. Some patients will receive oxygen therapy only
at night or when exercising.
The choice of type of home oxygen systems will
vary depending on availability, cost considerations,
and the mobility of the patient. Those patients who
GALE ENCYCLOPEDIA OF MEDICINE

Patients with sleep apnea will receive continuous
positive airway pressure to prevent upper airway collapse. It is usually administered through a tight-fitting
mask as humidified oxygen. The pressure of flow is
constant during both exhaling and inhaling and the
level of pressure is determined based on each individual. Most patients undergoing CPAP in a hospital
setting will receive continuous monitoring of some
vital signs and periodic sampling of blood gas values.
Oxygen chamber therapy
Also known as hyperbaric oxygen chamber or
hyperbaric oxygen therapy (HBO), this treatment
delivers pure oxygen under pressure equal to that of
2–3 times normal atmospheric pressure. For years, this
treatment has been especially effective on scuba divers
who suffer from the ‘‘bends,’’ or decompression illness.
The patient enters the chamber, a plastic cylindershaped structure that is normally transparent. In most
cases, just one patient will enter by being rolled into the
chamber on a type of stretcher. Once inside, the oxygen
will be delivered under forced pressure and the patient is
free to read, nap, or listen to the radio. The therapy
usually lasts one hour, although it can take up to five
2027

Inhalation therapies

have less success with this form of therapy for the
treatment of sleep apnea.

Inhalation therapies

hours in serious decompression cases. Before exiting the
chamber, the pressure will eventually be lowered to
normal atmospheric level.
Mechanical ventilation
In general, mechanical ventilation replaces or
supports the normal ventilatory lung function of a
patient. Although normally delivered in a hospital,
often to treat serious illness, mechanical ventilation
may be performed at home under the order and supervision of a physician and home health agency. The
patient will usually be intubated and the ventilator
machine ‘‘takes over’’ the breathing function.
There are several modes and methods of mechanical ventilation, each offering different advantages and
disadvantages. In assist/control ventilation, the oldest
mode of ventilation, the physician predetermines
settings and the ventilator delivers a breath each time
the patient makes an effort to inhale. In synchronized
intermittent mandatory ventilation, the machine
senses a patient’s effort to inhale and delivers the
preset amount. The amount cannot be increased by
the patient’s effort. Pressure-control ventilation
involves the physician’s selection of a peak pressure
and this method is most useful for patients suffering
from obstructive airways disease. In cases of severe
hypoventilation, an endotracheal tube must be
inserted. If a patient will be on mechanical ventilation
for more than two weeks, a tracheostomy, or surgical
incision, will be performed for placement of the
breathing tubes.
There are other modes of ventilation that may be
used, including high-frequency ventilation, a newer
technique that delivers 100 to 200 breaths per minute
to the patient. The breaths are delivered through a
humidified, high-pressure gas jet. High-frequency
ventilation may be ordered when a patient does not
respond to conventional mechanical ventilation or for
certain conditions and circumstances.
Newborn life support
Premature infants, especially those born before
the 28th week of gestation, have underdeveloped
breathing muscles and immature structures within
the lungs. These infants will require breathing support,
often in the form of mechanical ventilation. The
support delivers warm, humidified, oxygen-enriched
gases either by oxygen hood or through mechanical
ventilation. In serious cases, the infant may require
mechanical ventilation with CPAP or positive-end
expiratory pressure (PEEP) through a tightly fitting
face mask or even by endotracheal intubation.
2028

Need for continued resuscitation for newborns
depends not only on gestational age, but on signs
indicating ineffective breathing, including color,
heart rate, and respiratory effort. CPAP will be
delivered through nasal or endotracheal tubes with a
continuous-flow ventilator specifically designed for
infants. An alarm system alerts the neonatal staff to
problems and monitoring of breathing and other vital
functions will accompany the therapy. As respiratory
distress syndrome begins to resolve, usually in four or
five days, the type of support will be reduced accordingly and the infant may be weaned from the ventilator
and moved to only CPAP or an oxygen hood.

Preparation
Preparation for any of these treatments is normally not necessary, and in fact, these therapies may
be administered as a result of an emergency situation.
Some of the methods, particularly incentive spirometry, or at-home oxygen or ventilation, will require
education and cooperation with a home health agency
or respiratory therapist. Pretreatment testing of
various indicators of respiratory function and oxygen
saturation will be performed to determine exact needs
of individual patients.

Aftercare
Pulmonary function tests and other tests will be
performed to verify that treatments have been successful or to monitor and adjust treatments. Mechanical
ventilation will require weaning from the equipment
and may also require care for the area surrounding the
intubation.

Risks
Inhalation therapies may carry risks, complications or side effects including:
Oxygen therapy
At-home oxygen therapy carries risk if improper
care is taken to follow instructions when handling the
oxygen. Patients are cautioned not to smoke near the
oxygen supply and to keep the supply away from other
sources that may cause electrical spark, flames, or
intense heat. Patients on home oxygen therapy should
avoid use of sedatives.
Incentive spirometry
The major risk associated with incentive spirometry relates to improper use. Patients must be
GALE ENCYCLOPEDIA OF MEDICINE

disconnection. Mechanical ventilation increases risk
of infection in premature babies. Complications of
PEEP or CPAP may include pneumothorax or
decreased cardiac output.

Normal results
Oxygen therapy

Continuous positive airway pressure (CPAP)
The effectiveness of CPAP may be limited if
patients do not cooperate. Possible side effects of
CPAP include skin abrasions from the mask, leakage
from the tube or mask, nasal congestion, nasal or oral
dryness, or discomfort from the pressure of delivery.

In the case of COPD, oxygen therapy does not
treat the disease but can prolong life, quality of life,
and onset of more serious symptoms. Effective oxygen
therapy for any patient should lead to improved or
sustained levels of oxygen in arterial blood.
Incentive spirometry

Oxygen chamber therapy
Hyperbaric oxygen therapy is painless. The only
risk would be associated with improper administration of the pressure levels, which should not occur,
since respiratory staff and the supervising physician
should be thoroughly trained in performance of
this therapy. The drawback to hyperbaric oxygen
treatment is the limited availability of chambers.
Many cities do not have readily available chambers.
Mechanical ventilation
The biggest risk of mechanical ventilation is
sometimes considered to be a patient’s dependence
on the machine and the difficulty of weaning the
patient. The physician will carefully select and monitor the mode of ventilation, the machine’s settings,
and the patient’s progress to prevent this complication. A patient may therefore be left on a ventilator
after sufficient progress is made to gradually wean
breathing dependence.
Intubation and mechanical ventilation are frightening and uncomfortable for many patients and they
may fight the ventilator. If this occurs, the physician
may order a sedative to ensure cooperation and effectiveness of the therapy. Intubation often results in
irritation to the trachea and larynx. Tracheostomy is
associated with risk of bleeding, pneumothorax, local
infection, and increased incidence of aspiration.
Newborn life support
Infants are continuously monitored to determine
even small changes in breathing function. Mechanical
ventilation can result in increases in respiratory distress or other complications. It is possible for the
ventilator to be accidentally disconnected and staff
is trained to watch for signs or alarms indicating
GALE ENCYCLOPEDIA OF MEDICINE

With proper use of incentive spirometry, the
physician should observe improved pulse rate, decreased
respiratory rate, improved respiratory muscle performance, and other indicators of improved function.
Lung function following lung resection should show
marked improvement following incentive spirometry.
Continuous positive airway pressure
Successful CPAP will result in reduction in apnea
for those suffering from sleep apnea. A study reported
on in 1998 demonstrated that CPAP was effective in
the majority of patients with sleep apnea, with the
exception of significantly obese patients with blood
gas values that were worse during waking hours at
rest and at exercise. Hospitalized patients on CPAP
therapy should show improvement in blood gas and
other pulmonary measurements as expected by the
treating physician.
Oxygen chamber therapy
Divers undergoing emergency treatment in a hyperbaric chamber should show immediate improvement in
oxygen levels throughout the body, regardless of blood
flow restrictions, after one or two treatments. Those
patients receiving oxygen chamber therapy for difficult
wounds may continue to receive treatments daily for
several weeks before satisfactory results are reached.
Patients with carbon dioxide poisoning should show
improvement in or recovery of neurologic function.
Results of hyperbaric chamber therapy depend largely
on how quickly the patient was brought to the chamber,
as well as the severity of the initial condition.
Mechanical ventilation
Successful mechanical ventilation will result in
gradual decrease in dependence on the ventilator
2029

Inhalation therapies

carefully instructed in the technique and monitored
periodically for compliance and improvement.
Barotrauma, injury to the middle ear or sinuses
caused by imbalance between the affected cavity
and the outside, or ambient pressure, can result
form incentive spirometry. A patient may also suffer
discomfort or fatigue.

Insecticide poisoning

KEY TERMS
Aspiration—Accidental suction of fluids or vomit
into the respiratory system.
Cannula—A tube inserted into a cavity to serve as a
channel for the transport of fluid.
Endotracheal—Placed within the trachea.
Hypoventilation—Reduced ventilation in the
lungs’ air sacs resulting in above normal carbon
dioxide pressure.
Hypoxemia—A condition in which there is
deficient oxygen supply in the blood.
Hypoxia—Low levels of oxygen in blood, tissue,
or air.
Intubation—Placement of a tube into a hollow
organ (such as the trachea).
Pneumothorax—Presence of gas or air in the
hollow space around the lungs.
Trachea—The windpipe, or main by which air
passes to and from the lungs.

and weaning from the machine. Reduction of therapy
to another form, such as CPAP or oxygen therapy,
indicates that ventilation has worked as expected. In
the case of COPD, exacerbation may be successfully
treated with mechanical ventilation and the patient
may return to home oxygen therapy. Pediatric
patients will demonstrate normal growth and development as a normal result of long-term mechanical
ventilation at home. Some patients, particularly
those in a hospital intensive care unit, will not be
able to breathe again without the ventilator and
families and physicians will face tough choices
about continued life support.
Newborn life support
Neonates will be constantly monitored to measure lung function. Those measurements will help
caregivers determine if and when mechanical ventilation can be reduced and CPAP or oxygen mask
begun. CPAP is considered successful when the
infant’s respiratory rate is reduced by 30–40%, a
chest radiograph shows improved lung volume and
appearance, stabilization of oxygen levels is documented and caregivers observe improvement in the
infant’s comfort. Evidence that there is no infection
from ventilation is also considered normal. In some
cases, inhalation therapy, including mechanical
2030

ventilation, will not work and the infant’s parents
and physicians will face tough decisions about
invasive procedures with associated high risks or
cessation of life support.
Resources
ORGANIZATIONS

American Association for Respiratory Care. 11030 Ables
Lane, Dallas, TX 75229. (972) 243-2272, Fax (972)
484-2720.
American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://www.lungusa.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
OTHER

Hyperbaric Research and Treatment Center Page.
<http://www.hyperbaricrx.com>.

Teresa Odle

Inner ear infection see Labyrinthitis

Insecticide poisoning
Definition
Insecticide poisoning is exposure to a group of
chemicals designed to eradicate insects that cause
affected persons to develop clinical signs that can
progress to death.

Description
Insecticides belong to a group of chemicals called
organophosphates used to protect against insects.
Their use is popular since they are effective and do
not remain in the environment, disintegrating within
a few days. Organophosphates act to inhibit an
enzyme in humans called acetyl cholinesterase. This
enzyme functions to degrade a chemical called
acetylcholine, which excites nerve cells. The resultant
effect of organophosphates would be an increase in
acetylcholine, thus causing initial excitation of
nerve cells.
Poisoning can occur with a broad range of symptoms affecting the functioning of nerves and initial
symptoms similar to the flu such as vomiting, abdominal pain, dizziness, and headache. Common names
for insecticides include dichlorvos, chlorpyrifos, diazinon, fenthion, malathion, parathion, and carbamate. A special type of insecticide called paraquat is
GALE ENCYCLOPEDIA OF MEDICINE



Description of toxins: names of chemical(s).



Magnitude of exposure: determination of amount of
exposure.



Progression of symptoms: determining the progression of symptoms can provide information concerning life support and overall outcome.



Time of exposure: knowing the time of exposure is
vital since symptoms may be delayed, and it may
assist to develop a management plan.



Medical history: underlying diseases and therapeutic
mediations may worsen toxic manifestations.

Causes and symptoms
Exposure to insecticides can occur by ingestion,
inhalation, or exposure to skin or eyes. The chemicals
are absorbed through the skin, lungs, and gastrointestinal tract and then widely distributed in tissues.
Symptoms cover a broad spectrum and affect several
organ systems:


Gastrointestinal: nausea, vomiting, cramps, excess
salivation, and loss of bowel movement control



Lungs: increases in bronchial mucous secretions,
coughing, wheezing, difficulty breathing, and water
collection in the lungs (this can progress to breathing
cessation)



Skin: sweating



Eyes: blurred vision, smaller sized pupil, and
increased tearing



Heart: slowed heart rate, block of the electrical
conduction responsible of heartbeat, and lowered
blood pressure



Urinary system: urinary frequency and lack of
control



Central nervous system: convulsions, confusion,
paralysis, and coma

Diagnosis
The confirmatory diagnosis for insecticide
poisoning is the measurement of blood acetyl cholinesterase less than 50% of normal. The chemicals can
also be detected by specific urine testing. Signs and
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Acetylcholine—A chemical called a neurotransmitter that functions to excite nerve cells.
Acetylcholinesterase—An enzyme that breaks
down acetylcholine.
Central nervous system—Consists of the brain and
spinal cord and integrates and processes information.
Enzyme—A protein that speeds up a chemical
reaction, but is not consumed during the process.
Oxygen free radicals—Reactive molecules containing oxygen and can cause cell damage.

symptoms in addition to a comprehensive poisoning
assessment are essential for diagnosis. Carbamate
insecticide poisoning exhibits symptoms similar to
organophosphate poisoning but without central
nervous system signs.

Treatment
Decontaminate exposed clothing and wash with
soap and water immediately. Emergency measures
may focus on ventilator support and heart monitoring.
If inhalation is suspected, the patient should be
removed from the site of exposure. If the eyes were
the entry site, they should be flushed with large
amounts of water. If the chemicals were ingested, the
stomach may be washed out and activated charcoal
may be administered. Atropine or glycopyrrolate
(Robinul) is the drug of choice for carbamate insecticide poisoning. It reverses many symptoms, but is only
partially effective for central nervous symptom effects
such as coma and convulsions. A medication called
Pralidoxime is also commonly indicated to reactivate
acetylcholinesterase and to reverse typical symptoms
due to organophosphate poisoning. Additionally, the
patient is monitored for heart, lung, liver functioning,
specific blood tests, and oxygen levels in blood.

Prognosis
Prognosis depends on the specific chemical of exposure, magnitude and time of exposure, progression of
symptoms (severity), and onset for medical attention.

Prevention
Adherence to accepted guidelines for handling
and management is the key to preventing insecticide
2031

Insecticide poisoning

very lethal and responsible for approximately 1,000
deaths per year just in Japan. Paraquat poisoning
releases oxygen free radicals that destroy lung
and kidney tissues. When poisoning is suspected, a
comprehensive management and assessment plan
should be performed. This initial assessment should
include:

Insomnia

poisoning. These may include masks, gowns, gloves,
goggles, respiratory breathing machines, or hazardous
material suits.
Resources
BOOKS

Behrman, Richard E., et al, editors. Nelson Textbook. 16th
ed. W. B. Saunders Company, 2000.
Goldman, Lee, et al. Cecil’s Textbook of Medicine. 21st ed.
W. B. Saunders Company, 2000.
Rakel, Robert E., et al. Conn’s Current Therapy. 53rd ed.
W. B. Saunders Company, 2001.
PERIODICALS

Blain, P. G. ‘‘Effects of Insecticides.’’ Lancet 357 (5 May
2001).
OTHER

Material Safety Data Sheets. <http://oshweb.me.tut.fi>.
National Toxicology Program. <http://ntp-server.niehs.
nih.gov/main_Pages/NTP_ALL_STDY_PG.html>.

Laith Farid Gulli, M.D.

who are married, and it is more frequently reported by
those with lower socioeconomic status. Short-term, or
transient, insomnia is a common occurrence and
usually lasts only a few days. Long-term, or chronic
insomnia lasts more than three weeks and increases the
risk for injuries in the home, at the workplace, and
while driving because of daytime sleepiness and
decreased concentration. Chronic insomnia can also
lead to mood disorders like depression.

Causes and symptoms
Transient insomnia is often caused by a temporary situation in a person’s life, such as an argument
with a loved one, a brief medical illness, or jet lag.
When the situation is resolved or the precipitating
factor disappears, the condition goes away, usually
without medical treatment.
Chronic insomnia usually has different causes,
and there may be more than one. These include:


A medical condition or its treatment, including sleep
apnea



Use of substances such as caffeine, alcohol, and
nicotine



Psychiatric conditions such as mood or anxiety
disorders



Stress, such as sadness caused by the loss of a loved
one or a job



Disturbed sleep cycles caused by a change in work
shift



Sleep-disordered breathing, such as snoring



Periodic jerky leg movements (nocturnal myoclonus),
which happen just as the individual is falling asleep



Repeated nightmares or panic attacks during sleep.

Insomnia
Definition
Insomnia is the inability to obtain an adequate
amount or quality of sleep. The difficulty can be in
falling asleep, remaining asleep, or both. People with
insomnia do not feel refreshed when they wake up.
Insomnia is a common symptom affecting millions
of people that may be caused by many conditions,
diseases, or circumstances.

Description
Sleep is essential for mental and physical restoration. It is a cycle with two separate states: rapid eye
movement (REM), the stage in which most dreaming
occurs; and non-REM (NREM). Four stages of sleep
take place during NREM: stage I, when the person
passes from relaxed wakefulness; stage II, an early
stage of light sleep; stages III and IV, which are
increasing degrees of deep sleep. Most stage IV sleep
(also called delta sleep), occurs in the first several
hours of sleep. A period of REM sleep normally
follows a period of NREM sleep.
Insomnia is more common in women and older
adults. People who are divorced, widowed, or separated are more likely to have the problem than those
2032

Another cause is excessive worrying about
whether or not a person will be able to go to sleep,
which creates so much anxiety that the individual’s
bedtime rituals and behavior actually trigger insomnia. The more one worries about falling asleep, the
harder it becomes. This is called psychophysiological
insomnia.
Symptoms of insomnia
People who have insomnia do not start the day
refreshed from a good night’s sleep. They are tired.
They may have difficulty falling asleep, and commonly
lie in bed tossing and turning for hours. Or the individual may go to sleep without a problem but wakes in
the early hours of the morning and is either unable to
go back to sleep, or drifts into a restless unsatisfying
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
The diagnosis of insomnia is made by a physician
based on the patient’s reported signs and symptoms.
It can be useful for the patient to keep a daily record
for two weeks of sleep patterns, food intake, use of
alcohol, medications, exercise, and any other information recommended by the physician. If the patient has
a bed partner, information can be obtained about
whether the patient snores or is restless during
sleep. This, together with a medical history and
physical examination, can help confirm the doctor’s
assessment.
A wide variety of healthcare professionals can
recognize and treat insomnia, but when a patient
with chronic insomnia does not respond to treatment,
or the condition is not adequately explained
by the patient’s physical, emotional, or mental circumstances, then more extensive testing by a specialist in
sleep disorders may be warranted.

Treatment
Treatment of insomnia includes alleviating any
physical and emotional problems that are contributing
to the condition and exploring changes in lifestyle that
will improve the situation.
Changes in behavior
Patients can make changes in their daily routine
that are simple and effective in treating their insomnia.
They should go to bed only when sleepy and use the
bedroom only for sleep. Other activities like reading,
watching television, or snacking should take place
somewhere else. If they are unable to go to sleep,
they should go into another room and do something
that is relaxing, like reading. Watching television
should be avoided because it has an arousing effect.
The person should return to bed only when they feel
sleepy. Patients should set the alarm and get up every
morning at the same time, no matter how much they
have slept, to establish a regular sleep-wake pattern.
Naps during the day should be avoided, but if
absolutely necessary, than a 30 minute nap early in
the afternoon may not interfere with sleep at night.
Another successful technique is called sleeprestriction therapy, which restricts the amount of
GALE ENCYCLOPEDIA OF MEDICINE

time spent in bed to the actual time spent sleeping.
This approach allows a slight sleep debt to build up,
which increases the individual’s ability to fall asleep
and stay asleep. If a patient is sleeping five hours a
night, the time in bed is limited to 5–5 1/2 hours. The
time in bed is gradually increased in small segments,
with the individual rising at the same time each
morning; at least 85% of the time in bed must be
spent sleeping.
Drug therapy
Medications given for insomnia include sedatives,
tranquilizers, and antianxiety drugs. All require a doctor’s prescription and may become habit-forming.
They can lose effectiveness over time and can reduce
alertness during the day. The medications should be
taken two to four times daily for approximately three
to four weeks, though this will vary with the physician
and patient. If the insomnia is related to depression,
then an antidepressant medication may be helpful.
Over-the-counter drugs such as antihistamines are
not very effective in bringing about sleep and can
affect the quality of sleep.
Other measures
Relaxing before going to bed will help a person
fall asleep faster. Learning to substitute pleasant
thoughts for unpleasant ones (imagery training) is
a technique that can be very helpful in reducing
worry. Another effective measure is the use of
audiotapes which combine the sounds of nature
with soft relaxing music. These, alone or in combination with other relaxation techniques, can safely
promote sleepiness.
Changes in diet and exercise routines can also
have a have a beneficial effect. Dietary items to be
avoided include drinks that contain caffeine such as
coffee, tea and colas, chocolate (which contains a
stimulant), and alcohol, which initially makes a person sleepy but a few hours later can have the opposite
effect. Maintaining a comfortable bedroom temperature, reducing noise and eliminating light are also
helpful. Regularly scheduled morning or afternoon
exercise can relax the body. This should be done 3–4
times a week and be sufficient to produce a light
sweat.

Alternative treatments
Many alternative treatments are effective in treating both the symptom of insomnia and its underlying
causes. Incorporating relaxation techniques into
2033

Insomnia

sleep. This is a common symptom in the elderly and
in those suffering from depression. Sometimes sleep
patterns are reversed and the individual has difficulty
staying awake during the day and takes frequent naps.
The sleep at night is fitful and frequently interrupted.

Insulin resistance

OTHER

KEY TERMS
Biofeedback—A training technique that enables an
individual to gain some element of control over
involuntary body functions.
Mood disorder—A group of mental disorders involving a disturbance of mood, along with either a full
or partial excesseively happy (manic) or extremely
sad (depressive) syndrome not caused by any other
physical or mental disorder. Mood refers to a prolonged emotion.
Sleep apnea—A condition in which a person stops
breathing while asleep. These periods can last up to
a minute or more, and can occur many times each
hour. In order to start breathing again, the person
must become semi-awake. The episodes are not
remembered, but the following day the client feels
tired and sleepy. If severe, sleep apnea can cause
other medical problems.
Sleep disorder—Any condition that interferes with
sleep. At least 84 have been identified, according to
the American Sleep Disorders Association.

bedtime rituals will help a person go to sleep faster, as
well as improve the quality of sleep. These methods
include meditation, massage, breathing exercises, and
a warm bath, scented with rose, lavender (Lavendula
officinalis), marjoram, or chamomile (Matricaria
recutita). Eating a healthy diet rich in calcium, magnesium, and the B vitamins is also beneficial. A high
protein snack like yogurt before going to bed is recommended, or a cup of herb tea made with chamomile,
hops (Humulus lupulus), passionflower (Passiflora
incarnata), or St John’s Wort (Hypericum perforatum)
to encourage relaxation. Acupuncture and biofeedback
have also proven useful.

‘‘What to Do When You Can’t Sleep.’’ The Virtual Hospital
Page. University of Iowa. <http://www.vh.org>.

Donald G. Barstow, RN

Insulin see Antidiabetic drugs

Insulin resistance
Definition
Insulin resistance is not a disease as such but
rather a state or condition in which a person’s body
tissues have a lowered level of response to insulin, a
hormone secreted by the pancreas that helps to
regulate the level of glucose (sugar) in the body. As a
result, the person’s body produces larger quantities of
insulin to maintain normal levels of glucose in the
blood. There is considerable individual variation in
sensitivity to insulin within the general population,
with the most insulin-sensitive persons being as much
as six times as sensitive to the hormone as those identified as most resistant. Some doctors use an arbitrary
number, defining insulin resistance as a need for 200 or
more units of insulin per day to control blood sugar
levels. Various researchers have estimated that 3–16
percent of the general population in the United States
and Canada is insulin-resistant; another figure that is
sometimes given is 70–80 million Americans.
Insulin resistance can be thought of as a set of
metabolic dysfunctions associated with or contributing to a range of serious health problems. These
disorders include type 2 diabetes (formerly called
adult-onset or non-insulin-dependent diabetes), the
metabolic syndrome (formerly known as syndrome
X), obesity, and polycystic ovary syndrome. Some
doctors prefer the term ‘‘insulin resistance syndrome’’
to ‘‘metabolic syndrome.’’

Prevention
Prevention of insomnia centers around promotion
of a healthy lifestyle. A balance of rest, recreation and
exercise in combination with stress management, regular physical examinations, and a healthy diet can do
much to reduce the risk.
Resources
ORGANIZATIONS

American Sleep Disorders Association. 1610 14th St. NW,
Ste. 300, Rochester, MN 55901. (507) 287-6006.
<http://www.asda.org>.
2034

Description
To understand insulin resistance, it may be helpful
for the reader to have a brief account of the way
insulin works in the body. After a person eats a meal,
digestive juices in the small intestine break down
starch or complex sugars in the food into glucose, a
simple sugar. The glucose then passes into the bloodstream. When the concentration of glucose in the
blood reaches a certain point, the pancreas is stimulated to release insulin into the blood. As the insulin
reaches cells in muscle and fatty (adipose) tissues, it
GALE ENCYCLOPEDIA OF MEDICINE

The insulin may fail to bind to the insulin receptors for any of several reasons. Some persons inherit a
gene mutation that leads to the production of a defective form of insulin that cannot bind normally to the
insulin receptor. Others may have one of two types of
abnormalities in the insulin receptors themselves. In
type A, the insulin receptor is missing from the cell
surface or does not function properly. In type B, the
person’s immune system produces autoantibodies to
the insulin receptor.
In the early stages of insulin resistance, the
pancreas steps up its production of insulin in order
to control the increased levels of glucose in the blood.
As a result, it is not unusual for patients to have high
blood sugar levels and high blood insulin levels (a
condition known as hyperinsulinemia) at the same
time. If insulin resistance is not detected and treated,
however, the islets of Langerhans (the insulin-secreting groups of cells) in the pancreas may eventually
shut down and decrease in number.

Causes & symptoms



Other diseases and disorders. Some disorders—most
notably Cushing syndrome and cirrhosis—and such
stresses on the body as trauma, surgery, malnutrition,
or severe infections speed up the breakdown of
insulin or interfere with its effects.



Certain medications. Some drugs, including cyclosporine, niacin, and the protease inhibitors used to
treat HIV infection, may contribute to insulin
resistance.
Symptoms

The symptoms of insulin resistance vary considerably from person to person. Some people may have no
noticeable symptoms until they develop signs of heart
disease or are diagnosed with high blood pressure
during a routine checkup. Other patients may come
to the doctor with extremely high levels of blood sugar
(hyperglycemia) and such classical symptoms of
diabetes as thirst, frequent urination, and weight
loss. A small percentage of patients—most commonly
women with polycystic ovary syndrome—develop a
velvet-textured blackish or dark brown discoloration
of the skin known as acanthosis nigricans. This symptom, which is most commonly found on the neck,
groin, elbows, knees, knuckles, or armpits, is thought
to appear when high levels of insulin in the blood spill
over into the skin. This spillover activates insulin
receptors in the skin and causes it to develop an abnormal texture and color. Acanthosis nigricans occurs
more frequently in Hispanic and African American
patients than in Caucasians.

Causes
The reasons for the development of insulin resistance are not completely understood as of the early
2000s, but several factors that contribute to it have
been identified:


Genetic factors. Insulin resistance is known to run in
families. Genetic mutations may affect the insulin
receptor, the signaling proteins within cells, or the
mechanisms of glucose transport.



Obesity. Being overweight keeps the muscles from
using insulin properly, as it decreases the number of
insulin receptors on cell surfaces.



Low level of physical activity. Because muscle tissue
takes up 95 percent of the glucose that insulin helps the
body utilize (brain cells and blood cells do not depend
on insulin to help them use glucose), inactivity further
reduces the muscles ability to use insulin effectively.



Aging. The aging process affects the efficiency of
glucose transport.

GALE ENCYCLOPEDIA OF MEDICINE

Disorders associated with insulin resistance
Insulin resistance became an important field of
research in the late 1980s, when doctors first began
to understand it as a precondition of several common
but serious threats to health. As of the early 2000s,
insulin resistance is associated with the following
disorders:


Obesity. Obesity is not only the most common cause
of insulin resistance but is a growing health concern
in its own right. According to the National Institutes
of Health (NIH), the percentage of American adults
who meet the criteria for obesity rose from 25 percent
to 33 percent between 1990 and 2000—an increase of
a third within the space of a decade. Obesity is a risk
factor for the development of type 2 diabetes, high
blood pressure, and coronary artery disease.



Pre-diabetes and type 2 diabetes. The NIH estimates
that about 6.3 percent of the American population
has diabetes. Of these 18.3 million people, 5.2 million
are undiagnosed. Type 2 diabetes is much more
2035

Insulin resistance

attaches itself to molecules called insulin receptors on
the surface of the cells. The activation of the insulin
receptors sets in motion a series of complex biochemical signals within the cells that allow the cells to take
in the glucose and convert it to energy. If the pancreas
fails to produce enough insulin or the insulin receptors
do not function properly, the cells cannot take in
the glucose and the level of glucose in the blood
remains high.

Insulin resistance

common than type 1, accounting for 90–95 percent
of patients with diabetes. Diabetes increases a person’s risk of blindness, kidney disease, heart disease
and stroke, disorders of the nervous system, complications during pregnancy, and dental problems; it
also worsens the prognosis for such infectious diseases as influenza or pneumonia. About 41 million
Americans are thought to have pre-diabetes, which
is a condition marked by elevated levels of blood
glucose after fasting or after a 2-hour test for glucose
tolerance. According to the NIH, a majority of
pre-diabetic people will develop type 2 diabetes
within 10 years unless they lose between 5 and 7
percent of their body weight.




Heart disease. Insulin resistance has been linked to a
group of risk factors for heart disease and stroke
known as the metabolic syndrome (formerly called
syndrome X). The metabolic syndrome, like obesity,
has become increasingly prevalent in the United
States since the 1990s; as of the early 2000s, about a
quarter of the general adult population is thought to
have it, with the rate rising to 40 percent for adults
over the age of 60. To be diagnosed with the metabolic syndrome, a person must have three or more of
the following risk factors: a waist circumference
greater than 40 in (102 cm) in men or 35 in (88 cm)
in women; a level of blood triglycerides of 150 milligrams per deciliter (mg/dL) or higher; blood pressure
of 130/85 Hg or higher; fasting blood sugar level of
110 mg/dL or higher; and a blood level of highdensity lipoprotein (HDL) cholesterol (the so-called
‘‘good’’ cholesterol) lower than 50 mg/dL for men or
40 mg/dL for women.
Polycystic ovary syndrome (PCOS). PCOS is an
endocrine disorder that develops in 3–10 percent of
premenopausal women as a result of the formation
of cysts (small fluid-filled sacs) in the ovaries.
Women with PCOS do not have normal menstrual
periods; they are often infertile and may develop
hirsutism (excess body hair) or other indications of
high levels of androgens (male sex hormones) in the
blood. This condition is called hyperandrogenism,
and has been linked to insulin resistance in women
with PCOS. Weight loss in these patients usually
corrects hyperandrogenism and often restores
normal ovulation patterns and fertility.

Diagnosis
Patient history and physical examination
Because insulin resistance is a silent condition
in many people, the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK)
2036

recommends that all adults over the age of 45 be
tested for type 2 diabetes. People younger than 45
who are overweight and have one or more of the
following risk factors should also visit their doctor
to be tested:


One or more family members with diabetes.



High levels of triglycerides and low levels of HDL
cholesterol as defined by the criteria for metabolic
syndrome.



Hypertension (high blood pressure).



A history of smoking.



A history of diabetes during pregnancy (gestational
diabetes).



Giving birth to a baby weighing more than 9 pounds.
In addition to increasing the mother’s risk of developing type 2 diabetes, children who are large for their
gestational age (LGA) at birth have an increased
risk of developing insulin resistance and metabolic
syndrome in later life.



Having African American, Hispanic, Native
American, or Asian American/Pacific Islander
heritage.

Some signs and symptoms associated with insulin
resistance can be detected by a primary care physician
during a routine office visit. Blood pressure, weight,
body shape, and the condition of the skin can be
checked, as well as determining whether the patient
meets the criteria for obesity or is less severely overweight. Obesity is determined by the patient’s body
mass index, or BMI. The BMI, which is an indirect
measurement of the amount of body fat, is calculated
in English units by multiplying a person’s weight in
pounds by 703.1, and dividing that number by the
person’s height in inches squared. A BMI between
19 and 24 is considered normal; 25–29 is overweight;
30–34 is moderately obese; 35–39 is severely obese;
and 40 or higher is defined as morbidly obese. The
doctor may also evaluate the patient for obesity in
the office by measuring the thickness of the skinfold
at the back of the upper arm.
The distribution of the patient’s weight is also
significant, as insulin resistance is associated with a
so-called ‘‘apple-shaped’’ figure, in which much of the
excess weight is carried around the abdomen. People
whose excess weight is carried on the hips (the ‘‘pearshaped’’ figure) or distributed more evenly on the
body are less likely to develop insulin resistance. One
way of measuring weight distribution is the patient’s
waist-to-hip ratio; a ratio greater than 1.0 in men or
0.8 in women is strongly correlated with insulin
resistance.
GALE ENCYCLOPEDIA OF MEDICINE

There is no single laboratory test that can be used
to diagnose insulin resistance by itself as of 2005.
Doctors usually evaluate individual patients on the
basis of specific symptoms or risk factors. The tests
most commonly used include the following:


Blood glucose tests. A high level of blood glucose
may indicate either that the body is not producing
enough insulin or is not using it effectively. Two
common tests used to screen for insulin resistance
are the fasting glucose test and the glucose tolerance
test. In the fasting glucose test, the person takes no
food after midnight and has their blood glucose level
measured early in the morning. Normal blood glucose levels after several hours without food should be
below 100 milligrams per deciliter (mg/dL). If the
level is between 100 and 125 mg/dL, the person has
impaired fasting glucose (IFG) or pre-diabetes. If the
level is over 126 and is confirmed by a second test, the
person has diabetes. In the glucose tolerance test,
the person is given a sugar solution to drink and
their blood glucose level is measured 2 hours later.
A normal level is 140 mg/dL; 140–199 mg/dL
indicates impaired glucose tolerance (IGT) or prediabetes, while a level of 200 mg/dL or higher indicates diabetes.



Tests of blood insulin levels. These help to determine
whether high blood glucose levels are the result of
insufficient production of insulin or inefficient use
of insulin.



Lipid profile test. This test measures the amount of
total cholesterol, high-density lipoprotein (HDL)
cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. Patients with insulin resistance will have high levels of LDL cholesterol and
triglycerides with low levels of HDL cholesterol.



Measurement of blood electrolytes and uric acid.
Many patients with the metabolic syndrome have
high blood levels of uric acid.

A highly accurate technique for measuring insulin
resistance is called the euglycemic clamp technique.
The patient’s blood insulin level is kept (‘‘clamped’’)
at a high but steady level by continual insulin infusion
while the blood glucose level is monitored at frequent
intervals. Glucose concentrations in the blood are
maintained at a normal level by an adjustable-rate
glucose drip. The amount of glucose needed to maintain a normal blood glucose level over a given unit of
time indicates the degree of insulin resistance. This
test, however, requires complex equipment and careful
monitoring; it is considered too cumbersome to use in
routine screening and is used mostly by researchers.
GALE ENCYCLOPEDIA OF MEDICINE

Lifestyle modifications
Lifestyle modifications are the first line of treatment in dealing with insulin resistance:


Weight reduction. Losing weight increases the
body’s sensitivity to insulin. It is not necessary, however, for patients to reduce their weight to the ideal
levels listed on life insurance charts. In recent years,
researchers have found that even a modest weight
loss—usually defined as 10 percent of the patient’s
pretreatment weight—is enough to control or at least
improve insulin resistance and other health complications of obesity. Weight reduction is usually
accomplished by a combination of reduced calorie
intake and increased physical activity. Insulin sensitivity is reported to improve within a few days of
lowered calorie intake, even before the patient loses
a measurable amount of weight.



Exercise. Regular exercise improves the body’s sensitivity to insulin by increasing the muscles’ uptake of
glucose from the bloodstream, by increasing the
efficiency of the circulatory system and glucose
transport, and by reducing the amount of fat around
the patient’s abdomen. The American Academy of
Family Practice (AAFP) recommends 30 minutes of
moderately intense physical activity on most or all
days of the week for people diagnosed with insulin
resistance. Walking is a very good form of exercise
because it does not require any special equipment
other than comfortable walking shoes, can be combined with doing errands, and can be done either
alone or with a group of friends. Riding a bicycle is
another form of exercise recommended for weight
control.



Adding foods high in fiber to the diet. A diet high
in natural fiber, found in whole grains and vegetables, lowers the levels of blood insulin as well as
lowering the patient’s risk of developing high
blood pressure.



Quitting smoking. Giving up smoking lowers the risk
of heart disease, stroke, or lung cancer as well as
increasing the body’s sensitivity to insulin.



Limiting alcohol consumption. Alcohol is a source of
‘‘empty’’ calories with little nutritional value of its
own.
Medications

There are several different types of medications
that can be used to treat patients with abnormal blood
sugar or insulin levels:
2037

Insulin resistance

Treatment

Laboratory tests

Insulin resistance



Biguanides. Biguanides are drugs that improve the
body’s sensitivity to insulin by lowering the absorption of glucose in the small intestine, decreasing the
liver’s production of glucose, and increasing the
uptake of glucose in muscle and fatty tissues.
Metformin (Glucophage), a drug used in the treatment of type 2 diabetes, is the most commonly used
biguanide in treating insulin resistance. It has also
been studied as a possible treatment in preventing or
delaying the onset of type 2 diabetes.



Thiazolidinediones. These drugs stimulate glucose
uptake in the muscles and fatty tissues by activating
specific receptors in the cell nucleus. They also lower
blood insulin levels in patients with hyperinsulinemia. The thiazolidinediones include pioglitazone
(Actos) and rosiglitazone (Avandia).



Glucocorticoids. These drugs may be given to
patients with insulin resistance caused by anti-insulin
antibodies produced by their immune system.
Prednisone (Deltasone) is the most commonly used
glucocorticoid.



Insulin itself. Some patients with insulin resistance
benefit from injectable insulin to reduce their blood
sugar levels.

As of early 2005, however, the Food and Drug
Administration (FDA) has not approved any drugs
for the treatment of insulin resistance by itself. For this
reason, the American Diabetes Association does not
recommend treating insulin resistance with medications unless the patient has already been diagnosed
with diabetes.
The patient’s doctor may also prescribe medications to treat specific health problems associated with
insulin resistance. These drugs may include diuretics
and other medications to lower blood pressure; aspirin
to reduce the risk of heart attack; medications to lower
the levels of triglycerides and LDL cholesterol in the
blood; and weight-control drugs. The drugs most
frequently prescribed in the early 2000s to help
patients lose weight are orlistat (Xenical) and sibutramine (Meridia).
Acanthosis nigricans may be treated with topical preparations containing Retin-A, 20% urea,
or salicylic acid; however, many patients find that
the skin disorder improves by itself following
weight loss.
Surgery
Insulin resistance by itself does not require surgical treatment; however, patients who have already
developed heart disease may require coronary artery
2038

bypass surgery. In addition, very obese patients—
those with a BMI of 40 or higher—may benefit from
bariatric surgery. Bariatric surgery includes such
procedures as vertical banded gastroplasty and gastric
bypass, which limit the amount of food that the
stomach can contain.

Alternative treatment
Some alternative treatments for insulin resistance and type 2 diabetes have been studied by
the Agency for Healthcare Research and Quality
(AHRQ). One study reported in 2004 that omega-3
fatty acids, a dietary supplement commonly derived
from fish, canola, or soybean oil, did not appear to
have any significant effect on blood sugar levels or
blood insulin levels in patients diagnosed with type
2 diabetes or the metabolic syndrome. An earlier
study of Ayurvedic medicine, the traditional medical system of India, reported in 2001 that certain
herbs used to make Ayurvedic medicines, such as
fenugreek, holy basil, Coccinia indica, and
Gymnema sylvestre appear to be effective in lowering blood sugar levels and merit further study.
The AHRQ report also noted that the Ayurvedic
practice of combining herbal medicines with yoga
and other forms of physical activity should be
investigated further.
Other alternative treatments for insulin resistance
and type 2 diabetes include chromium supplements,
ginseng, biofeedback, and acupuncture. The connection between chromium supplementation and insulin
resistance is that the body needs chromium to produce
a substance called glucose tolerance factor, which
increases the effectiveness of insulin. Further studies
need to be done, however, before recommendations
about dietary chromium as a treatment for insulin
resistance can be made.

Prognosis
Since insulin resistance is a condition that precedes the appearance of symptoms of a number of
different disorders, its prognosis depends in part on
the patient’s age, ethnicity, family history, and severity
of any current health problems. Some patients
diagnosed with insulin resistance eventually develop
type 2 diabetes, but it is not yet known why the others
do not; for example, some patients do not develop
diabetes in spite of a high degree of insulin resistance.
What is known at present is that weight reduction and
exercise can control or even reverse insulin resistance
in many people.
GALE ENCYCLOPEDIA OF MEDICINE

Acanthosis nigricans—A dark brownish or blackish
discoloration of the skin related to overweight and
high levels of insulin in the blood. Acanthosis nigricans is most likely to develop in the groin or armpits,
or around the back of the neck.
Bariatrics—The branch of medicine that deals with
the prevention and treatment of obesity and related
disorders.
Body mass index (BMI)—A measurement that has
replaced weight as the preferred determinant of
obesity. The BMI can be calculated (in English
units) as 703.1 times a person’s weight in pounds
divided by the square of the person’s height in inches.
Glucose—A simple sugar produced when carbohydrates are broken down in the small intestine. It is
the primary source of energy for the body. Various
tests that measure blood glucose levels are used in
diagnosing insulin resistance.
Hyperandrogenism—Excessive secretion of androgens (male sex hormones).
Hyperinsulinemia—The medical term for high levels
of insulin in the blood.
Insulin—A protein hormone secreted by the islets of
Langerhans in the pancreas in response to eating.
Insulin carries glucose and amino acids to muscle
and adipose cells and promotes their efficient use
and storage.
Islets of Langerhans—Special structures in the pancreas responsible for insulin secretion among other
functions. They are named for Paul Langerhans,
the German researcher who first identified them in
1869.
Lipids—A group of fats and fat-like substances that
are not soluble in water, are stored in the body, and
serve as a source of fuel for the body.

Prevention
Genetic factors contributing to insulin resistance
cannot be changed as of the early 2000s.
With regard to lifestyle factors, the National
Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) reported the findings of a study
of the effects of lifestyle changes or metformin on
the incidence of diabetes in a group of over 3200
overweight people with impaired glucose tolerance,
GALE ENCYCLOPEDIA OF MEDICINE

Metabolic syndrome—A group of risk factors for
heart disease, diabetes, and stroke. It includes
abdominal obesity, high blood pressure, high blood
glucose levels, and low levels of high-density
lipoprotein (HDL) cholesterol. The metabolic syndrome is sometimes called the insulin resistance
syndrome.
Metabolism—The sum of an organism’s physical and
chemical processes that produce and maintain living
tissue, and make energy available to the organism.
Insulin resistance is a disorder of metabolism.
Obesity—Excessive weight gain due to accumulation of fat in the body, sometimes defined as a BMI
of 30 or higher, or body weight greater than 30
percent above one s desirable weight on standard
height-weight tables.
Pancreas—A large gland located behind the stomach
near the spleen that secretes digestive enzymes into
the small intestine and insulin into the bloodstream.
Syndrome—In general, a set of symptoms that occur
together as signs of a disease or disorder.
Syndrome X—A term that was sometimes used for
metabolic syndrome when the syndrome was first
identified in the 1960s.
Triglycerides—Fatty compounds synthesized from
carbohydrates during the process of digestion and
stored in the body’s adipose (fat) tissues. High levels
of triglycerides in the blood are associated with
insulin resistance.
Type 2 diabetes mellitus—One of the two major
types of diabetes mellitus, characterized by late age
of onset (30 years or older), insulin resistance, high
levels of blood sugar, and little or no need for supplemental insulin. It was formerly known as adult-onset
or non-insulin-dependent diabetes.

which is a risk factor for developing type 2 diabetes.
The researchers found that the subjects in the lifestyle modification group, who lowered their food
intake and took 30-minute walks five days a week,
had a 58-percent lower incidence of diabetes. The
subjects who received metformin had a 31-percent
lower incidence of diabetes. Lifestyle changes were
most effective in volunteers over the age of 60,
while metformin was most effective in younger subjects. In short, the 2002 study confirmed the
2039

Insulin resistance

KEY TERMS

Insulin resistance

beneficial effects of lowered food intake and
increased activity as preventive measures against
type 2 diabetes.
Another important part of preventing insulin resistance is patient education. A number of resources on
weight control and exercise written for the general
public are available from the Weight-Control
Information Network (WIN) on the NIDDK website
at http://win.niddk.nih.gov/publications/physical.htm.
Some pamphlets are available in Spanish as well as
English. Patient education materials on insulin resistance in relation to heart disease and diabetes can be
downloaded free of charge from the American Heart
Association and American Diabetes Associan websites.
Resources
BOOKS

‘‘Diabetes Mellitus.’’ Section 2, Chapter 13 in The Merck
Manual of Diagnosis and Therapy, edited by Mark H.
Beers, MD, and Robert Berkow, MD. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Flancbaum, Louis, MD, with Erica Manfred and Deborah
Biskin. The Doctor’s Guide to Weight Loss Surgery.
West Hurley, NY: Fredonia Communications, 2001.
‘‘Nutritional Disorders: Obesity.’’ Section 1, Chapter 5 in
The Merck Manual of Diagnosis and Therapy, edited by
Mark H. Beers, MD, and Robert Berkow, MD.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine.
New York: Simon & Schuster, 2002.
PERIODICALS

Boney, C. M., A. Verma, R. Tucker, and B. R. Vohr.
‘‘Metabolic Syndrome in Childhood: Association with
Birth Weight, Maternal Obesity, and Gestational
Diabetes Mellitus.’’ Pediatrics 115 (March 2005):
290–296.
Diabetes Prevention Program Research Group. ‘‘Reduction
in the Incidence of Type 2 Diabetes with Lifestyle
Intervention or Metformin.’’ New England Journal of
Medicine 346 (February 7, 2002): 393–403.
Ford, Earl S., MD, MPH, Wayne H. Giles, MD, MSc, and
William H. Dietz, MD, PhD. ‘‘Prevalence of the
Metabolic Syndrome Among US Adults.’’ Journal of
the American Medical Association 287 (January 16,
2002): 356–359.
Litonjua, P., A. Pinero-Pilona, L. Aviles-Santa, and
P. Raskin. ‘‘Prevalence of Acanthosis Nigricans in
Newly-Diagnosed Type 2 Diabetes.’’ Endocrine
Practice 10 (March–April 2004): 101–106.
Olatunbosun, Samuel, MD, and Samuel Dagogo-Jack, MD.
‘‘Insulin Resistance.’’ eMedicine, 3 June 2004. <http://
www.emedicine.com/med/topic1173.htm>.
Rao, Goutham, MD. ‘‘Insulin Resistance Syndrome.’’
American Family Physician 63 (March 15, 2001):
1159–1166.
2040

Scheinfeld, N. S. ‘‘Obesity and Dermatology.’’ Clinical
Dermatology 22 (July-August 2004): 303–309.
Sivitz, William I., MD. ‘‘Understanding Insulin Resistance:
What Are the Clinical Implications?’’ Postgraduate
Medicine 116 (July 2004): 41–48.
ORGANIZATIONS

American Academy of Dermatology (AAD). P. O. Box
4014, Schaumburg, IL 60168-4014. (847) 330-0230.
Fax: (847) 330-0050. <http://www.aad.org>.
American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.
American Heart Association National Center. 7272
Greenville Avenue, Dallas, TX 75231. (800) 242-8721.
<http://www.americanheart.org>.
American Obesity Association (AOA). 1250 24th Street
NW, Suite 300, Washington, DC 20037. (202) 776-7711
or (800) 98-OBESE. <www.obesity.org>.
National Diabetes Information Clearinghouse (NDIC).
1 Information Way, Bethesda, MD 20892-3560. (800)
860-8747. Fax: (703) 738-4929.
OTHER

Agency for Healthcare Research and Quality (AHRQ).
Evidence Report/Technology Assessment: Number 41.
Ayurvedic Interventions for Diabetes Mellitus.
Rockville, MD: AHRQ, 2001. <http://www.ahrq.gov/
clinic/epcsums/ayurvsum.htm>.
Agency for Healthcare Research and Quality (AHRQ).
Evidence Report/Technology Assessment: Number 89.
Effects of Omega-3 Fatty Acids and Glycemic Control in
Type II Diabetes and the Metabolic Syndrome and on
Inflammatory Bowel Disease, Rheumatoid Arthritis,
Renal Disease, Systemic Lupus Erythematosus, and
Osteoporosis. Rockville, MD: AHRQ, 2004. <http://
www.ahrq.gov/clinic/epcsums/o3lipidsum.htm>.
Mayo Clinic Staff. Metabolic Syndrome. <http://
www.mayoclinic.com/invoke.cfm?id=DS00522>.
National Diabetes Information Clearinghouse (NDIC).
Insulin Resistance and Pre-Diabetes. NIH Publication
No. 04-4893. Bethesda, MD: National Institute of
Diabetes and Digestive and Kidney Diseases
(NIDDK), 2004. <http://diabetes.niddk.nih.gov/dm/
pubs/insulinresistance>.
National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) News Brief, 6 February 2002. ‘‘Diet
and Exercise Delay Diabetes and Normalize Blood
Glucose.’’ <http://www.niddk.nih.gov/welcome/
releases/02-06-02.htm>.

Rebecca Frey, PhD

Intelligence tests see Stanford-Binet intelligence scales; Wechsler intelligence test
Intention tremor see Tremors
GALE ENCYCLOPEDIA OF MEDICINE

two to three times increased risk of coronary heart
disease, stroke, or cardiac failure in men with diabetes,
according to the association.

Interleukin-2 see Immunologic therapies
Causes & symptoms

Intermittent claudication
Definition
Intermittent claudicationis a pain in the leg that
a person experiences when walking or exercising.
The pain is intermittent and goes away when the
person rests.

Description
Claudication comes from the Latin word that
means ‘‘to limp,’’ and the condition is characterized
by intermittent pain in the leg muscles. Poor circulation produces the pain. The legs do not receive the
oxygen-rich blood supply needed for activities like
walking and exercising. The decreased blood flow is
caused by the narrowing of arteries that bring blood to
the leg and foot.
The leg pain produced by claudication is usually
experienced as cramping in the thighs, calves, hips,
and feet. The pain stops several minutes after the
person rests, but returns when the person performs
activities that use the leg muscles. If untreated, claudication is no longer intermittent and occurs when a
person is resting.
People age 50 or older are at risk of intermittent
claudication. The risk increases with age. Statistically,
5% of men and 2.5% of women experience symptoms
of this condition, according to the Vascular Disease
Foundation (VDF). Many people with this condition
have cholesterol plaque build-up in the leg’s arteries.
Smoking raises the risk, as do high blood pressure,
obesity, lack of exercise, and diabetes.
Intermittent claudication is the main symptom of
peripheral arterial disease (PAD), which is also known
as peripheral vascular disease, and or occlusive arterial
disease. Intermittent claudication is an early symptom
of the condition that affects peripheral arteries, those
blood vessels located outside the heart. PAD is caused
by arteriosclerosis, the narrowing and hardening of
the arteries.
Women with diabetes are 7.6 times as likely to
experience PAD as those without diabetes, according
to the American Diabetes Association (ADA).
Furthermore, intermittent claudication is related to a
GALE ENCYCLOPEDIA OF MEDICINE

Intermittent claudication is caused by poor circulation and is experienced in a person’s muscle groups.
It affects the peripheral arteries that convey oxygenrich blood from the heart to the legs. A person with
this condition feels pain shortly after beginning to
exercise. Walking may trigger the pain in an inactive
person. Activities such as climbing stairs, walking
rapidly or dancing can cause the pain to increase.
The person feels the pain as tightness in the calf,
thigh, or buttocks. The pain stops after the person
rests for several minutes. However, it returns when
the person reaches the exertion level that previously
produced the pain.
Intermittent claudication is the primary symptom
of PAD, the condition causing reduced flow of blood
and oxygen to tissues. If the intermittent condition is
not treated, the person will find that resting does not
relieve pain. As arteries become more clogged, the
person could feel pain even when not exercising.
Symptoms include cold or numb feet and toes, poor
balance when standing, a drop in leg strength, sores
that heal slowly, and erectile dysfunction (impotence).
In the advanced stages of PAD, the person experiences pain when resting. This condition, ischemic
rest pain, is characterized by symptoms visible on the
feet and toes. These include ulcers, loss of hair, and
the change to red color when feet are suspended.
Other symptoms include blue or purple markings on
the legs, feet and toes. The coloring is a sign that
less oxygen is reaching these areas. Furthermore,
black skin on the legs and feet is a sign of gangrene
infection.

Diagnosis
People experiencing symptoms of intermittent
claudication should contact their doctor immediately.
The doctor will review the patient’s medical history
and examine the person for signs of the condition.
This examination includes checking for a lower pulse
or the absence of a pulse behind the knee, on the ankle,
foot, and groin.
The doctor may order an ankle-brachial index
(ABI) test to determine whether arteries are blocked.
This procedure will verify if the person has PAD and
provides information on the severity of the condition.
The ABI measures blood pressure in the arms and
2041

Intermittent claudication

Interferon see Antiviral drugs; Immunologic
therapies

Intermittent claudication

ankle. Readings are taken when the person is at rest
and after exercising lightly by walking on a treadmill.
The ABI index is found by dividing the ankle blood
pressure by the pressure for the arm. An ABI below
0.90 in a person at rest is a sign of PAD.
The physician may also order a Doppler ultrasound exam to measure the flow of blood through
the arteries. Cuffs are placed on four places on each
leg. The doctor then moves an ultrasound probe over
arteries in the foot. The probe detects signals from
the artery.
Testing can last from 20 minutes to an hour. Costs
vary by location and facility. In March of 2005, the
ABI test was priced from $45 to $150. Some facilities
offered a package of tests for around $200. The
procedures are usually covered by medical insurance.

Treatment
Lifestyle changes are the primary form of treating
intermittent claudication. Physicians advise people to
quit smoking, exercise, and to follow the American
Heart Association’s healthy diet guidelines. Diabetics
need to control blood sugar levels. The patient may
need to lower blood pressure and cholesterol levels.
Those measurements should drop when a person
makes lifestyle changes.
The goal of treatment is stop development of
PAD. By exercising, eating a diet that includes fiber
and low-fat foods, and not smoking, a person could
also reverse the build-up that clogs arteries. After
several months of this regimen, many people experience a lessening of leg pain. If pain continues, the
doctor may prescribe medication. Furthermore, surgery may be needed in some cases.
Walking
Walking is frequently an important treatment for
intermittent claudication. A person experiencing the
pain of intermittent claudication may not feel like
walking. However, walking can increase the capacity
to exercise. Before starting an exercise program, the
person should consult with consult with a doctor.

according to the Vascular Disease Foundation. The
person walks until pain is moderately severe. A rest
period is scheduled after the person walks eight to 10
minutes.
The person walks and rests, with the goal of
walking for a total of 35 minutes. The person walks
at least three times weekly. If a treadmill is not available, VDF recommends that people walk on a track.
Generally, a person walking three times weekly will be
able to walk longer after three to 12 months.
Medications
People diagnosed with PAD are at a high risk
for a stroke and heart attack. They should take
aspirin to reduce this risk. Clopidogrel, a drug marketed as Plavix, worked even better than aspirin in a
study. However, it was more costly, with 30 tablets
selling for about $119 in 2005. The dosage is one
tablet daily.
A doctor may also prescribe cilostazol—sold under
the name Pletal—which extends the distance people
can walk without pain. One tablet is taken twice
daily. The medication cost around $112 for 60 tablets.
Surgical procedures
Surgical procedures may be necessary in cases
where intermittent claudication is disabling. The person experiences pain when resting, has open sores that
do not heal, or symptoms of gangrene like dying skin
in the leg or foot.
Bypass surgery directs blood through a grafted
blood vessel, bypassing the damaged artery. The
grafted vessel is either a healthy artery or vein or an
artificial vessel.
Angioplasty is a procedure to open blocked blood
vessels. A catheter (tube) is inserted in the groin and
moved to the artery. Then a tiny balloon is inflated to
open the artery. Another angioplasty procedure
involves the insertion of a stent, a metal device that
keeps the vessel open.

The physician reviews the patient’s medical history, does a physical and may order an exercise stress
test on a treadmill. The test shows how long a person
walks before claudication starts. Information such as
blood pressure is used to evaluate the person’s ability
to walk. The findings are also used to develop a medically supervised exercise program.

Angioplasty is a minimally invasive procedure.
Local anesthesia is used, and a person is able to resume
normal activities within one to two days. The cost
averaged $6,502, according to a 2001 Dartmouth
Medical School study. Bypass surgery cost $12,422
on average, according to the study. A non-invasive
procedure is not as risky as surgery. However, a
bypass may be needed when multiple sections of
blood vessels are blocked.

At the beginning, the treadmill is set to cause
claudication symptoms in three to five minutes,

Once a person is diagnosed with intermittent
claudication, health plans usually cover part of

2042

GALE ENCYCLOPEDIA OF MEDICINE

Arthrosclerosis—A condition where fatty deposits
cause the arteries to narrow.
Gangrene—The decay of tissue in the body; it is
caused by an obstruction to the blood supply.

People can learn more about peripheral vascular
disease through public education programs like the
free Legs for Life screenings held at sites across
the nation. The program started the Society of
Interventional Radiology features a free ABI testing.
Resources
PERIODICALS

treatment costs. A study on the overall costs of this
condition from diagnosis through treatment should be
completed by the end of 2005, according to a Sheryl
Benjamin, VDF executive director.

‘‘New Treatment for Leg Pain–Conference News
Update.’’Clinician Reviews, April 2002 [cited
March 25, 2005]. <http://www.findarticles.com/p/
articles/mi_m0BUY/is_4_12/ai_86050499>.
Warkentin, Donald L. ‘‘Intermittent Claudication.’’ Clinical
Reference Systems. January 1, 2004, 1813.
ORGANIZATIONS

Alternative treatment
Ginkgo biloba extract, an herbal remedy, has been
used by people with intermittent claudication. The
extract made from the dried leaves of the Gingko
tree is thought to improve blood flow, allowing people
to walk longer without pain.
However, herbal remedies are not regulated the
U.S. Food and Drug Administration, and people should
consult with their doctors before taking Ginkgo.
Furthermore, use of this remedy could interact adversely
when taken with Vitamin E and some medications.

Prognosis
If untreated, intermittent claudication will
advance and eventually restrict a person’s mobility.
In later stages, people feel pain when resting. The leg
or foot may feel cold. In the extreme stage, the person
might need a cane, walker, or wheelchair. There is
more risk of gangrene developing, and amputation
might be necessary. Diabetics face an increased risk
of amputation.
PAD also increases the risk of heart attacks and
strokes.

Prevention
A healthy lifestyle is the best method for preventing intermittent claudication. Cigarette smokers
should quit smoking. Regular exercise and a healthy
diet help reduce the risk of this condition. If necessary,
people should work to lower cholesterol and blood
pressure. Diabetics should strive to manage that
condition, obese people should lose weight.
The methods of preventing intermittent claudication are also the means for managing the risks
associated with a diagnosis of PAD.
GALE ENCYCLOPEDIA OF MEDICINE

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. 800-342-2383. <http://
www.diabetes.org>.
Society of Interventional Radiology. 10201 Lee Highway,
Suite 500, Fairfax, VA 22030. 703-691-1805. <http://
www.sirweb.org/index.shtml>.
Vascular Disease Foundation. 1075 S. Yukon Street, Suite
320, Lakewood, CO 80226. 866-723-4636. <http://
www.vdf.org/Contact_Frame.htm>.
OTHER

‘‘Intermittent Claudication: 8 Ways to Ease the Pain.’’ The
Doctors Book of Home Remedies, Rodale. [cited
March 25, 2005]. <http://www.mothernature.com/
Library/Bookshelf/Books/47/85.cfm>.
‘‘Peripheral Arterial Disease of the Legs.’’ Kaiser
Permanente. Updated November 3, 2003
[cited March 25, 2005].<http://
prospectivemembers.kaiserpermanente.org>.

Liz Swain

Intermittent explosive
disorder
Definition
Intermittent explosive disorder (IED) is a mental
disturbance that is characterized by specific episodes
of violent and aggressive behavior that may involve
harm to others or destruction of property. IED is
discussed in the Diagnostic and Statistical Manual of
Mental Disorders fourth edition (DSM-IV) under
the heading of ‘‘Impulse-Control Disorders Not
Elsewhere Classified.’’ As such, it is grouped together
with kleptomania, pyromania, and pathological
gambling.
2043

Intermittent explosive disorder

KEY TERMS

Intermittent explosive disorder

A person must meet certain specific criteria to be
diagnosed with IED:


IED, however, and have reported it as part of
premenstrual syndrome (PMS).

There must be several separate episodes of failure to
restrain aggressive impulses that result in serious
assaults against others or property destruction.



The degree of aggression expressed must be out of
proportion to any provocation or other stressor
prior to the incidents.



The behavior cannot be accounted for by another
mental disorder, substance abuse, medication side
effects, or such general medical conditions as
epilepsy or head injuries.

The reader should note that DSM-IV’s classification of IED is not universally accepted. Many
psychiatrists do not place intermittent explosive
disorder into a separate clinical category but consider
it a symptom of other psychiatric and mental disorders. In many cases individuals diagnosed with IED
do in fact have a dual psychiatric diagnosis. IED is
frequently associated with mood and anxiety disorders, substance abuse and eating disorders, and narcissistic, paranoid, and antisocial personality disorders.

Description
People diagnosed with IED sometimes describe
strong impulses to act aggressively prior to the specific
incidents reported to the doctor and/or the police.
They may experience racing thoughts or a heightened
energy level during the aggressive episode, with fatigue
and depression developing shortly afterward. Some
report various physical sensations, including tightness
in the chest, tingling sensations, tremor, hearing
echoes, or a feeling of pressure inside the head.
Many people diagnosed with IED appear to have
general problems with anger or other impulsive
behaviors between explosive episodes. Some are able
to control aggressive impulses without acting on them
while others act out in less destructive ways, such as
screaming at someone rather than attacking them
physically.
Although the editors of DSM-IV stated in 2000
that IED ‘‘is apparently rare,’’ a group of researchers
in Chicago reported in 2004 that it is more common
than previously thought. They estimate that 1.4 million
persons in the United States currently meet the criteria
for IED, with a total of 10 million meeting the lifetime
criteria for the disorder.
With regard to sex and age group, 80% of individuals diagnosed with IED in the United States are
adolescent and adult males. Women do experience
2044

Causes and symptoms
Causes
As with other impulse-control disorders, the cause
of IED has not been determined. As of 2004, researchers disagree as to whether it is learned behavior, the
result of biochemical or neurological abnormalities, or
a combination of factors. Some scientists have
reported abnormally low levels of serotonin, a neurotransmitter that affects mood, in the cerebrospinal
fluid of some anger-prone persons, but the relationship of this finding to IED is not clear. Similarly, some
individuals diagnosed with IED have a medical history
that includes migraine headaches, seizures, attentiondeficit hyperactivity disorder, or developmental
problems of various types, but it is not clear that
these cause IED, as most persons with migraines,
learning problems, or other neurological disorders do
not develop IED.
Some psychiatrists who take a cognitive approach
to mental disorders believe that IED results from rigid
beliefs and a tendency to misinterpret other people’s
behavior in accordance with these beliefs. According
to Dr. Aaron Beck, a pioneer in the application of
cognitive therapy to violence-prone individuals, most
people diagnosed with IED believe that other people
are basically hostile and untrustworthy, that physical
force is the only way to obtain respect from others, and
that life in general is a battlefield. Beck also identifies
certain characteristic errors in thinking that go along
with these beliefs:


Personalizing. The person interprets others’ behavior
as directed specifically against him.



Selective perception. The person notices only those
features of situations or interactions that fit his negative view of the world rather than taking in all available information.



Misinterpreting the motives of others. The person
tends to see neutral or even friendly behavior as
either malicious or manipulative.



Denial. The person blames others for provoking his
violence while denying or minimizing his own role in
the fight or other outburst.
Symptoms

The symptoms of IED are described by the DSM-IV
criteria for diagnosing the disorder.
GALE ENCYCLOPEDIA OF MEDICINE

The diagnosis of IED is basically a diagnosis of
exclusion, which means that the doctor will eliminate
such other possibilities as neurological disorders,
mood or substance abuse disorders, anxiety syndromes, and personality disorders before deciding
that the patient meets the DSM-IV criteria for IED.
In addition to taking a history and performing a physical examination to rule out general medical conditions, the doctor may administer one or more
psychiatric inventories or screeners to determine
whether the person meets the criteria for other mental
disorders.
In some cases the doctor may order imaging studies or refer the person to a neurologist to rule out
brain tumors, traumatic injuries of the nervous system, epilepsy, or similar physical conditions.

Treatment
Emergency room treatment
A person brought to a hospital emergency room
by family members, police, or other emergency personnel after an explosive episode will be evaluated by
a psychiatrist to see whether he can safely be released
after any necessary medical treatment. If the patient
appears to be a danger to himself or others, he may be
committed against his will for further treatment. In
terms of legal issues, a doctor is required by law to
notify the specific individuals as well as the police if
the patient threatens to harm particular persons. In
most states, the doctor is also required by law to
report suspected abuse of children, the elderly, or
other vulnerable family members.
The doctor will perform a thorough medical
examination to determine whether the explosive outburst was related to substance abuse, withdrawal from
drugs, head trauma, delirium, or other physical conditions. If the patient becomes assaultive inside the hospital, he may be placed in restraints or given
a tranquilizer (usually either lorazepam [Ativan]
or diazepam [Valium]), most often by injection. In
addition to the physical examination, the doctor will
obtain as detailed a history as possible from the family
members or others who accompanied the patient.
Medications
Medications that have been shown to be beneficial
in treating IED in nonemergency situations include
lithium, carbamazepine (Tegretol), propranolol
(Inderal), and such selective serotonin reuptake inhibitors as fluoxetine (Prozac) and sertraline (Zoloft).
GALE ENCYCLOPEDIA OF MEDICINE

Adolescents diagnosed with IED have been reported
to respond well to clozapine (Clozaril), a drug normally used to treat schizophrenia and other psychotic
disorders.
Psychotherapy
Some persons with IED benefit from cognitive
therapy in addition to medications, particularly if
they are concerned about the impact of their disorder
on their education, employment, or interpersonal relationships. Psychoanalytic approaches are not useful in
treating IED.

Prognosis
The prognosis of IED depends on several factors
that include the individual’s socioeconomic status, the
stability of his or her family, the values of the surrounding neighborhood, and his or her motivation to change.
One reason why the Chicago researchers think that
IED is more common than previously thought is that
most people who meet the criteria for the disorder do
not seek help for the problems in their lives that result
from it. The researchers found that although 88% of
the 253 individuals with IED that they studied were
upset by the results of their explosive outbursts, only
13% had ever asked for treatment in dealing with it.

Prevention
Since the cause(s) of IED are not fully understood
as of the early 2000s, preventive strategies should
focus on treatment of young children (particularly
boys) who may be at risk for IED before they enter
adolescence.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders, 4th ed., revised.
Washington, D.C.: American Psychiatric Association,
2000.
Beck, Aaron T., MD. Prisoners of Hate: The Cognitive Basis
of Anger, Hostility, and Violence. New York:
HarperCollins Publishers, 1999.
Beers, Mark H., MD., and Robert Berkow, MD, editors.
‘‘Psychiatric Emergencies.’’ Section 15, Chapter 194.
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Citrome, Leslie L., MD, MPH, and Jan Volavka, MD.
‘‘Aggression.’’ eMedicine. February 8, 2002.
<http://www.emedicine.com/Med/topic3005.htm>.
2045

Intermittent explosive disorder

Diagnosis

Intersex states

OTHER

KEY TERMS
Cognitive therapy—A form of short-term psychotherapy that focuses on changing people’s patterns of emotional reaction by correcting distorted
patterns of thinking and perception.
Delirium—An acute but temporary disturbance of
consciousness marked by confusion, difficulty paying attention, delusions, hallucinations, or restlessness. Delirium may be caused by drug intoxication,
high fever related to infection, head trauma, brain
tumors, kidney or liver failure, or various metabolic
disturbances.
Kleptomania—A mental disorder characterized by
impulsive stealing.
Neurotransmitter—Any of a group of chemicals
that transmit nerve impulses across the gap
(synapse) between two nerve cells.
Pyromania—A mental disorder characterized by
setting fires.
Serotonin—A neurotransmitter or brain chemical
that is responsible for transporting nerve impulses.

Coccaro, E. F., C. A. Schmidt, J. F. Samuels, and
G. Nestadt. ‘‘Lifetime and 1-Month Prevalence Rates
of Intermittent Explosive Disorder in a Community
Sample.’’ Journal of Clinical Psychiatry 65 (June 2004):
820–824.
Grant, J. E., and M. N. Potenza. ‘‘Impulse Control
Disorders: Clinical Characteristics and
Pharmacological Management.’’ Annals of
Clinical Psychiatry 16 (January–March 2004):
27–34.
Kant, R., R. Chalansani, K. N. Chengappa, and M. F.
Dieringer. ‘‘The Off-Label Use of Clozapine in
Adolescents with Bipolar Disorder, Intermittent
Explosive Disorder, or Posttraumatic Stress Disorder.’’
Journal of Child and Adolescent Psychopharmacology
14 (Spring 2004): 57–63.
McElroy, Susan L. ‘‘Recognition and Treatment of DSMIV Intermittent Explosive Disorder.’’ Journal of Clinical
Psychiatry (1999): 12–16.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry.
3615 Wisconsin Avenue, NW, Washington, DC
20016-3007. (202) 966-7300. Fax: (202) 966-2891.
<http://www.aacap.org>.
American Psychiatric Association. 1400 K Street, NW,
Washington, DC 20005. <http://www.psych.org>.
National Institute of Mental Health. 6001 Executive
Boulevard, Room 8184, MSC 9663, Bethesda, MD
20892-9663. (301) 443-4513. <http://www.nimh.nih.gov>.
2046

Padgitt, Steven T. ‘‘Treating Intermittent Explosive
Disorder with Neurofeedback’’ Behavenet.com. May 7,
2001. <http://www.behavenet.com/capsules/disorders/explosivedis.htm>.

Janie F. Franz
Rebecca Frey, PhD

Internal fetal monitoring see Electronic fetal
monitoring
Internuclear ophthalmoplegia see
Ophthalmoplegia
Interpositional reconstruction see
Arthroplasty

Intersex states
Definition
Intersex states are conditions where a newborn’s
sex organs (genitals) look unusual, making it impossible to identify the sex of the baby from its outward
appearance.

Description
All developing babies start out with external
sex organs that look female. If the baby is male, the
internal sex organs mature and begin to produce the
male hormone testosterone. If the hormones reach
the tissues correctly, the external genitals that looked
female change into the scrotum and penis. Sometimes,
the genetic sex (as indicated by chromosomes) may not
match the appearance of the external sex organs.
About 1 in every 2,000 births results in a baby whose
sex organs look unusual.
Patients with intersex states can be classified as a true
hermaphrodite, a female pseudohermaphrodite, or a
male pseudohermaphrodite. This is determined by examining the internal and external structures of the child.
A true hermaphrodite is born with both ovaries and
testicles. They also have mixed male and female external
genitals. This condition is extremely rare.
A female pseudohermaphrodite is a genetic
female. However, the external sex organs have been
masculinized and look like a penis. This may occur if
the mother takes the hormone progesterone to prevent
GALE ENCYCLOPEDIA OF MEDICINE

Chromosomes—Spaghetti-like structures located
within the nucleus (or central portion) of each
cell. Chromosomes contain the genetic information
necessary to direct the development and functioning of all cells and systems in the body. They pass
on hereditary traits from parents to child (like eye
color) and determine whether the child will be
male or female.

This infant was born with female and male genitalia.
(Photography by Mike Peres, Custom Medical Stock Photo.
Reproduced by permission.)

a miscarriage, but more often it is caused by an overproduction of certain hormones.
A male pseudohermaphrodite is a genetic male.
However, the external sex organs fail to develop normally. Intersex males may have testes and a femalelike vulva, or a very small penis.

Causes and symptoms
Any abnormality in chromosomes or sex hormones, or in the unborn baby’s response to the
hormones, can lead to an intersex state in a newborn.
Intersex states may also be caused by a condition
called congenital adrenal hyperplasia, which occurs in
about 1 out of every 5,000 newborns. This disease
blocks the baby’s metabolism and can cause a range
of symptoms, including abnormal genitals.

Diagnosis
When doctors are uncertain about a newborn’s sex,
a specialist in infant hormonal problems is consulted as
soon as possible. Ultrasound can locate a uterus behind
the bladder and can determine if there is a cervix or
uterine canal. Blood tests can check the levels of sex
hormones in the baby’s blood, and chromosome analysis (called karyotyping) can determine sex.
Explorative surgery or a biopsy of reproductive tissue
may be necessary. Only after thorough testing can a
correct diagnosis and determination of sex be made.

Treatment
Treatment of intersex states is controversial.
Traditional treatment assigns sex according to test
GALE ENCYCLOPEDIA OF MEDICINE

results, the potential for the child to identify with a
sex, and the ease of genital surgery to make the organs
look more normal. Treatment may then include reconstructive surgery followed by hormone therapy. Babies
born with congenital adrenal hyperplasia can be
treated with cortisone-type drugs and sometimes
surgery.
Counseling should be given to the entire family of
an intersex newborn. Families should explore all available medical and surgical options. Counseling should
also be provided to the child when he or she is old
enough.

Prognosis
Since the mid-1950s, doctors have typically
assigned a sex to an intersex infant based on how
easy reconstructive surgery would be. The American
Academy of Pediatrics states that children with these
types of genitals can be raised successfully as members
of either sex, and recommends surgery within the first
15 months of life.
Some people are critical of this approach,
including intersex adults who were operated on as
children. The remolded genitals do not function
sexually and can be the source of lifelong pain.
They suggest that surgery be delayed until the
patient can make informed choices about surgery
and intervention.
Resources
ORGANIZATIONS

Ambiguous Genitalia Support Network. P.O. Box 313,
Clements, CA 95227. (209) 727-0313.
Intersex Society. P.O. Box 31791, San Francisco, CA 94131.

Carol A. Turkington
2047

Intersex states

KEY TERMS

Interstitial microwave thermal therapy

Interstitial microwave thermal
therapy
Definition
Interstitial microwave thermal therapy is a type of
hyperthermia treatment for cancer, in which heat
produced by microwaves (which are a non-ionizing
form of radiation) is used in conjunction with other
cancer treatments, such as radiation or chemotherapy,
to kill cancer cells associated with tumors located deep
with the body.

Purpose
The purpose of interstitial microwave thermal
therapy is to damage and kill cancer cells associated
with tumors that are deep within the body. Interstitial
microwave therapy is a type of hyperthermia cancer
treatment procedure (also called thermal therapy or
thermotherapy) in which body tissue and the cancerous tumor are exposed to high temperatures (up to
1138F). Hyperthermia kills cancer cells with usually
only minimal injury to normal tissues by damaging
proteins and structures within the cells. Thermal
therapy is usually used with other forms of cancer
therapy, such as radiation and chemotherapy. The
increased temperatures may make some cancer cells
more sensitive to radiation or may harm some cancer
cells that radiation cannot damage.

Precautions
If a patient has become insensitive to pain due to
disease, radiation, surgery, anesthetics, or other conditions, hyperthermia treatment cannot be used to treat
tumors. Also the excessive heating of normal surrounding tissue is prevented by normal blood perfusion,
so hyperthermia should not be used in patients with
known circulatory problems in the heated areas or in
patients who are taking vasoconstrictive drugs.

Description
Interstitial microwave thermal therapy is used to
treat tumors that are deep within the body, such as
brain, cervical, breast, prostate, and neck tumors.
This technique allows the tumor to be heated to higher
temperatures than external thermal therapy techniques
allow. Probes or needles are inserted into the tumor,
guided by the use of imaging techniques, such as ultrasound, to make sure that the probe is properly located
within the tumor. A new type of microwave generator
includes electronic phase control that allows the
2048

operator to electronically direct and shape the pattern
of hyperthermia treatments based on the positioning
the microwave antennae array that is used in treating
the tumor. The treatment pattern can be electronically
targeted on the tumor position, shape, and size.
Tissues are heated as the electromagnetic energy
produced by the microwave treatment results in heating through molecular excitation. This energy is dissipated in normal living tissue by the blood that
perfuses through the tissue. However, since large
solid malignant tumors have less blood perfusion
than the surrounding normal tissue, for a given
absorbed thermal dose, the tumor reaches a higher
temperature than the normal tissue. Tumors present
within normal tissue will therefore be preferentially
heated and will reach higher temperatures than the
surrounding tissue.
As cancerous tumors grow rapidly, their need for
blood quickly begins to exceed the available blood
supply, and major portions of the tumors become
blood-starved. These blood-starved tumors are
resistant to both radiation and chemotherapy.
Chemotherapy drugs carried through the blood
cannot effectively penetrate tumors that have poor
blood flow. Poor blood flow also means that the
tumors are oxygen-starved (hypoxic), making it difficult for radiation therapy to make the oxygen radicals
that are needed to destroy the DNA of cancer cells.
Hypoxic cancer cells, which are an especially dangerous type of cancer, for they have a tendency to
metastasize and spread the cancer to other parts of
the body, are three times more resistant to ionizing
radiation than are normal cells.
When the tumor is heated to fever levels through
the use of microwave thermal therapy, its blood vessels
expand so that more blood can flow into the tumor in
order to carry away the excess heat. With the increased
blood flow, more blood-borne chemotherapy drugs
can be carried into the tumor. Blood is also the source
of oxygen for tumors, so with increased blood flow
due to the thermal therapy, radiation therapy can
form the necessary oxygen radicals to kill the cancer
cells. The increased temperature also acts as a drug
activator, accelerating chemical reactions and pulling
increased oxygen molecules into the tumor tissue
for chemical reactions with the chemotherapy drug.
Hypothermia also enhances the effectiveness of chemotherapy drugs encapsulated in liposomes, increasing the penetration of the drug into the tumor.
When tumors are heated to higher temperatures
for at least an hour, the tumors in some cases have
been shown to decrease in size and to exhibit necrosis
GALE ENCYCLOPEDIA OF MEDICINE

Hyperthermia is being studied as a means of
enhancing gene therapy by acting as an activator to
turn on new biological therapies, by speeding up gene
production by thousands of times. In addition,
hyperthermia is used as an essential tool to turn on
anti-tumor vaccines that are based on heat shock proteins. Hyperthermia has been shown to prevent a cancererous tumor from growing new blood vessels to
expand its blood supply. With regards to quality of
life, hyperthermia lessens pain and stimulates the
immune system, thus helping patients recover from
toxic cancer therapies such as ionizing radiation and
chemotherapy. Even in patients with terminal cancer,
hyperthermia can provide benefits through the alleviation of bleeding, pain, and infection.
As of 2005, the use of hyperthermia alone and in
conjunction with radiation therapy has been approved
by the United States Food and Drug Administration
for the treatment of advanced, recurrent, and persistent tumors, upon authorization of a licensed practitioner. When used with radiation, the treatment
regimen usually consists of 10 hyperthermia treatments delivered twice a week, at 72 hour intervals.
The prescribed radiation is administered within
30 minutes of the hyperthermia treatment. During
each heat treatment, the temperature within the tumor
is usually maintained at 42.5 degrees centigrade for
60 minutes. The use of hyperthermia in conjunction
with chemotherapy is presently investigational in the
United States as of 2005.
The effectiveness of treatment is related to the
temperature achieved during the treatment process,
the length of the treatment, and cell and tissue characteristics. The temperature within the tumor must be
monitored to ensure that the appropriate temperature
is achieved, but not exceeded, in the treatment area.
Monitoring is accomplished by inserting small needles
or tubes with small thermometers into the treatment
area. Imaging techniques such as computed tomography (CT) are used to make sure that the temperature
probes are positioned appropriately.

Preparation
The safety and effectiveness of hyperthermia
treatment is dependent on careful placement of the
GALE ENCYCLOPEDIA OF MEDICINE

temperature probes and careful monitoring of tissue
temperatures during treatment.

Aftercare
During the treatment period, which may last for
weeks, the patient must be instructed in proper care of
implanted catheters and temperature probe sites to
avoid the risk of infection.

Risks
Excessive heating of normal tissues may result in
areas of thermal aseptic necrosis that will require
medical care. The electromagnetic radiation from the
microwave equipment can interfere with electronic
devices such as cardiac pacemakers or other implanted
electronic devices. Thermal treatment of tumors in the
neck or head may result in inadvertent heating of
thermoregulatory centers in the brain stem, thus
resulting in overheating of the body, beyond levels
that the patient can tolerate. Metallic implants, such
as joint protheses or dental braces may become excessively and preferentially overheated and adversely
affect the patient.

Normal results
The effectiveness of interstitial microwave thermal therapy varies among cancer patients. For example, studies have shown in Phase III clinical trials,
when hyperthermia was used with ionizing radiation
treatment, that the following treatment improvements
were seen, as compared to the use of ionizing radiation
therapy alone:


complete response for recurrent breast cancer
increased from 38% to 60%



2-year survival for globlastoma (brain cancer)
increased from 15% to 31%



complete response for advanced cervical cancer
increased from 57% to 83%

Known side effects of hypothermia are associated
with direct effects of heat on tissues and indirect effects
of tumor necrosis. These side effects, as determined in
various medical studies, include:


surface burns and blistering in the area of application
of heat by the microwave applicators; experienced in
about 10% of the tumor sites studied.



localized and temporary pain in the area of and
during the delivery of the heat by the microwave
applicators; experienced in about 8% of the tumor
sites studied.
2049

Interstitial microwave thermal therapy

(death of the tumor cells). Therefore, hyperthermia by
itself also tends to shrink tumors, often dramatically,
due to the collapse of dead cancer cells, making it
easier to remove the tumor by surgical techniques.
For tumors of the head and neck, a smaller tumor
due to hyperthermia treatment may reduce the disfiguration associated with surgical removal of the tumor.

Intestinal obstructions

KEY TERMS
Blood perfusion—A physiological term that refers
to the process of nutritive delivery of arterial blood
to a capillary bed in the biological tissue.
Hyperthermia therapy—A type of treatment in
which body tissue is exposed to high temperatures
to damage and kill cancer cells or to make cancer
cells more sensitive to the effects of radiation and
certain anticancer drugs.
Non-ionizing radiation—Rays of energy that move
in long, slow wave patterns and do not penetrate
cells.t
Ionizing radiation—Any electromagnetic or particulate radiation capable of producing ions, directly
or indirectly, in its passage through matter.





ulceration from rapid tumor necrosis following
successful hyperthermia treatment, resulting in
fever from toxemia and patient discomfort through
drainage and bleeding; experienced in about 4% of
the tumor sites studied.
local and systematic (rarely) infections from placement of the temperature probes and from ulceration
related to tumor necrosis; experienced in about 2%
of the tumor sites studied.

Abnormal results
Hyperthermia has the potential for producing the
following adverse reactions as a result of exposure to
electromagnetic radiation:


cataracts



permanent or temporary male sterility



exacerbation of existing diseases due to additional
systemic stress



enhanced drug activity



thermal stress

Resources
BOOKS

Rosenbaum, Ernest, Dollinger, Malin, Tempero, Margaret,
and Mulvihill, Sean. Everyone’s Guide to Cancer
Therapy. 4th Edition. Kansas City, KS: Andrews
McMeel Publishing, 2002
PERIODICALS

Falk, M.H., and Issels, R.D. ‘‘Hyperthermia in Oncology.’’
International Journal of Hyperthermia. 2001, (17) 1–18.
2050

van der Zee, J. ‘‘Heating the Patient: A Promising
Approach?’’ Annals of Oncology 2002, (13) 1173–1184.
Wust, P., Hildebrandt, B., Sreenivasa, G. et al.
‘‘Hyperthermia in Combined Treatment of Cancer.’’
The Lancet Oncology 2002, (3) 487–497.
ORGANIZATION

Hyperthermia in Cancer Treatment. National Cancer
Institute. <www.cis.nci.gov/fact/7_3.htm>
Society for Thermal Medicine. <www.thermaltherapy.org>.

Judith L. Sims

Intestinal culture see Stool culture
Intestinal lymphangiectasia see
Malabsorption syndrome

Intestinal obstructions
Definition
Intestinal obstruction refers to the partial or
complete mechanical or nonmechanical blockage of
the small or large intestine.

Description
There are two types of intestinal obstructions,
mechanical and nonmechanical. Mechanical obstructions occur because the bowel is physically blocked
and its contents cannot get past the obstruction.
Mechanical obstructions can occur for several reasons. Sometimes the bowel twists on itself (volvulus)
or telescopes into itself (intussusception). Mechanical
obstruction can also result from hernias, impacted
feces, abnormal tissue growth, the presence of foreign bodies in the intestines (including gallstones),
or inflammatory bowel disease (Crohn’s disease).
Nonmechanical obstruction, called ileus, occurs
because the wavelike muscular contractions of the
intestine (peristalsis) that ordinarily move food
through the digestive tract stop.
Mechanical obstruction in infants
Infants under one year of age are most likely to
have intestinal obstruction caused by meconium ileus,
volvulus, and intussusception. Meconium ileus, which
is the inability to pass the first fecal excretion after
birth (meconium), is a disorder of newborns. It is an
early clue that the infant has cystic fibrosis, but may
also occur in very low birth weight (VLBW) infants.
In meconium ileus, the material that is blocking the
GALE ENCYCLOPEDIA OF MEDICINE

Volvulus is the medical term for twisting of either
the small or large bowel. The twisting may cut off the
blood supply to the bowel, leading to tissue death
(gangrene). This development is called a strangulating
obstruction.
In intussusception, the bowel telescopes into itself
like a radio antenna folding up. Intussusception is
most common in children between the ages of three
and nine months, although it also occurs in older
children. Almost twice as many boys suffer intussusception as girls. It is, however, difficult for doctors to
predict which infants will suffer from intestinal
obstruction.
Mechanical obstruction in adults
Obstructions in adults are usually caused by
tumors, trauma, volvulus, the presence of foreign
bodies such as gallstones, or hernias, although they
have also been reported in adults with cystic fibrosis.
Volvulus occurs most often in elderly adults and
psychiatrically disturbed patients. Intussusception in
adults is usually associated with tumors in the bowel,
whether benign or malignant.
More recently, gastroenterologists have described
a postsurgical complication known as early postoperative small bowel obstruction, or EPSBO. Although this
condition was at one time confused with postoperative
ileus, it is now known to be caused by mechanical
obstructions resulting from radiation therapy for cancer
or laparoscopic surgery. Most casses can be succesfully
treated within 10–14 days of surgery.

Causes and symptoms
One of the earliest signs of mechanical intestinal
obstruction is abdominal pain or cramps that come
and go in waves. Infants typically pull up their legs and
cry in pain, then stop crying suddenly. They will then
behave normally for as long as 15–30 minutes, only to
start crying again when the next cramp begins. The
cramping results from the inability of the muscular
contractions of the bowel to push the digested food
past the obstruction.
Vomiting is another symptom of intestinal
obstruction. The speed of its onset is a clue to the
location of the obstruction. Vomiting follows shortly
after the pain if the obstruction is in the small intestine
but is delayed if it is in the large intestine. The vomited
GALE ENCYCLOPEDIA OF MEDICINE

material may be fecal in character. When the patient
has a mechanical obstruction, the doctor will first hear
active, high-pitched gurgling and splashing bowel
sounds while listening with a stethoscope. Later these
sounds decrease, then stop. If the blockage is complete, the patient will not pass any gas or feces. If the
blockage is only partial, however, the patient may
have diarrhea. Initially there is little or no fever.
When the material in the bowel cannot move past
the obstruction, the body reabsorbs large amounts of
fluid and the abdomen becomes sore to the touch and
swollen. The balance of certain important chemicals
(electrolytes) in the blood is upset. Persistent vomiting
can cause the patient to become dehydrated. Without
treatment, the patient can suffer shock and kidney
failure.
Strangulation occurs when a loop of the intestine
is cut off from its blood supply. Strangulation occurs
in about 25% of cases of small bowel obstruction. It is
a serious condition that can progress to gangrene
within six hours.

Diagnosis
Imaging studies
If the doctor suspects intestinal obstruction based
on the physical examination and patient history, he or
she will order x rays, a computed tomography scan
(CT scan), or an ultrasound evaluation of the abdomen.
In many cases the patient is given a barium enema.
Barium sulfate, which is a white powder, is inserted
through the rectum and the intestinal area is photographed. Barium acts as a contrast material and allows
the location of the obstruction to be pinpointed on film.
Laboratory tests
The first blood test of a patient with an intestinal
obstruction usually gives normal results, but later tests
indicate electrolyte imbalances. There is no way to
determine if an obstruction is simple or strangulated
except surgery.

Treatment
Initial assessment
All patients with suspected intestinal obstruction
are hospitalized. Treatment must be rapid, because
strangulating obstructions can be fatal. The first step
in treatment is inserting a nasogastric tube to suction
out the contents of the stomach and intestines. The
patient is then given intravenous fluids to prevent
dehydration and correct electrolyte imbalances.
2051

Intestinal obstructions

intestine is thick and stringy, rather than the collection
of mucus and bile that is passed by normal infants. The
abnormal meconium must be removed with an enema
or through surgery.

Intestinal obstructions

KEY TERMS
Electrolytes—Salts and minerals that ionize in body
fluids. Electrolytes control the body’s fluid balance
as well as performing other important functions.
Gangrene—The death of soft tissue in any part of
the body when the blood supply is obstructed.
Ileus—Obstruction of the intestines caused by the
absence of peristalsis.
Intussusception—The slipping or telescoping of
one part of the intestine into the section next to it.
Meconium—A greenish fecal material that forms
the first bowel movement of an infant.
Peristalsis—The waves of muscular contraction in
the intestines that push the food along during the
process of digestion.
Strangulated obstruction—An obstruction in which
a loop of the intestine has its blood supply cut off.
Volvulus—A twisting of the intestine that causes an
obstruction.

particularly the use of high-fiber diets to keep the
bowels healthy through regular elimination.

Prognosis
Mortality
Untreated intestinal obstructions can be fatal.
Delayed diagnosis of volvulus in infants has a mortality rate of 23–33% with prompt diagnosis and
treatment the mortality rate is 3–9%. The bowel either
strangulates or perforates, causing massive infection.
With prompt treatment, however, most patients
recover without complications.
Recurrence
As many as 80% of patients whose volvulus is
treated without surgery have recurrences. Recurrences
in infants with intussusception are most likely to happen during the first 36 hours after the blockage has been
cleared. The mortality rate for unsuccessfully treated
infants is 1–2%.

Prevention
Nonsurgical approaches
Surgery can be avoided for some patients. In some
cases of volvulus, guiding a rectal tube into the intestines will straighten the twisted bowels. In infants,
a barium enema may reverse intussusception in
50–90%. An air enema is sometimes used instead of
a barium enema. This treatment successfully relieves
the obstruction in many infants. The children are
usually hospitalized for observation for two to three
days after these procedures. In patients with only
partial obstruction, a barium enema may dissolve the
blockage.
Surgical treatment
If these efforts fail, surgery is necessary.
Strangulated obstructions require emergency surgery.
The obstructed area is removed and part of the bowel
is cut away. If the obstruction is caused by tumors,
polyps, or scar tissue, they are removed. Hernias, if
present, are repaired. Antibiotics are given to reduce
the possibility of infection.

Alternative treatment
Alternative practitioners offer few suggestions for
treatment. They focus on preventive strategies,
2052

Most cases of intestinal obstruction are not preventable. Surgery to remove tumors, polyps, or gallstones helps prevent recurrences.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Mechanical Intestinal Obstruction.’’ Section 3,
Chapter 25. In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Chahine, A. Alfred, MD. ‘‘Intussusception.’’ eMedicine
June 10, 2004. <http://www.emedicine.com/ped/
topic1208.htm>.
Dray, X., T. Bienvenu, N. Desmazes-Dufeu, et al. ‘‘Distal
Intestinal Obstruction Syndrome in Adults with Cystic
Fibrosis.’’ Clinical Gastroenterology and Hepatology
2 (June 2004): 498–503.
Emil, S., T. Nguyen, J. Sills, and G. Padilla. ‘‘Meconium
Obstruction in Extremely Low-Birth-Weight Neonates:
Guidelines for Diagnosis and Management.’’ Journal of
Pediatric Surgery 39 (May 2004): 731–737.
Hebra, Andre, MD, and Melissa Miller, MD. ‘‘Intestinal
Volvulus.’’ eMedicine February 25, 2004. <http://
www.emedicine.com/ped/topic1205.htm>.
Sajja, S. B., and M. Schein. ‘‘Early Postoperative Small
Bowel Obstruction.’’ British Journal of Surgery 91
(June 2004): 683–691.
GALE ENCYCLOPEDIA OF MEDICINE

Location of intestinal polyps

HealthAnswers.com. ‘‘Intestinal Obstruction.’’ <http://
www.healthanswers.com/database/ami/converted/
000260.html>.
‘‘Intussusception: A Case Study for Nurses.’’ University of
New Brunswick Nursing Faculty Page. <http://
www.unb.ca/courses/nur4284/intu.htm>.

Tish Davidson, A.M.
Rebecca Frey, PhD

Intestinal polyps
Definition
The word polyp refers to any overgrowth of tissue
from the surface of mucous membranes. Intestinal
polyps grow out of the lining of the small and large
bowels. Polyps come in a variety of shapes–round,
droplet, and irregular being the most common.

Description
Polyps are one of many forms of tissue overproduction that can occur in the body. Cells in many
body tissues sometimes keep growing beyond their
usual limits. Medical scientists call this process neoplasia, which means simply ‘‘new growth.’’ An individual
overgrowth is called a neoplasm. In most cases these
growths are limited, and the result is a benign swelling
or mass of cells called a tumor. If the new growth
occurs on the surface of the tissue instead of inside
an organ it is often called a polyp. Cancer is another
type of neoplasm marked by unlimited tissue growth.
The essential feature that distinguishes cancer from
nonmalignant neoplasms is that it does not stop
growing.
Intestinal polyps are a common form of neoplasm. All intestinal polyps arise from the inner lining
of the intestinal wall. This layer of mucosal tissue does
the work of digestion. About 30% of the general
population will develop intestinal polyps at some
point in life, with the likelihood increasing with age.
Most of these polyps are never noticed during a
person’s lifetime because they cause no problems.
They are often discovered accidentally at autopsy.
The primary importance of intestinal polyps is that
1% of them become cancerous. Because the polyps
that eventually turn malignant cannot be identified
in advance, they are all suspect.
GALE ENCYCLOPEDIA OF MEDICINE

The chances of a polyp’s becoming cancerous
depend to some extent on its location within the
digestive tract.
COLON. Ninety-five percent of all intestinal
polyps develop inside the large bowel. There are
several hereditary diseases that produce large numbers
of intestinal polyps. These disorders include:


Familial polyposis of the colon.



Gardner’s syndrome.



Lynch’s syndrome.



Turcot’s syndrome.



Peutz-Jeghers syndrome.



Juvenile polyposis.

All of these disorders are inherited in what is
called an autosomal dominant pattern. This pattern
means that the disorders are not sex-linked and that a
child can inherit the disorder from either parent. In all
of these hereditary disorders, the intestinal polyps
appear during or after puberty. The first four diseases
on the list have such a high rate of cancer of the large
bowel (colon)–virtually 100% by the age of 40–that
persons diagnosed with any of them should have the
colon removed surgically in early adulthood.
STOMACH. The stomach’s lining is host to polyps
of a similar appearance, but there is no agreement as to
their potential for becoming stomach cancer.
SMALL INTESTINE. Polyps in the small bowel do not
seem to have malignant potential. Instead they can
produce obstruction in either of two ways. A large
polyp can obstruct the bowel by its sheer size.
Smaller polyps can be picked up by the rhythmic
contractions (peristalsis) of the intestines and pull the
part of the bowel to which they are attached into the
adjoining section. The result is a telescoping of one
section of bowel into another, called intussusception.

Causes and symptoms
Population studies of colon cancer suggest that
diet plays an important role in the disease, and by
implication in the formation of colon polyps. The
most consistent interpretation of these data is that
animal fats—though not vegetable fats—are the single
most important dietary factor. Lack of fiber in the diet
may also contribute to polyp formation. Other types
of polyps are too rare to produce enough data for
evaluation.
Most polyps cause no symptoms. Large ones eventually cause intestinal obstruction, which produces
2053

Intestinal polyps

OTHER

Intrauterine growth retardation

Prevention

KEY TERMS
Autosomal dominance—A pattern of heredity in
which a trait is inherited without respect to sex and
from either parent. The hereditary diseases associated
with intestinal polyps are all autosomal dominant.
Colectomy—Surgical removal of the large bowel.
Intussusception—The slipping of one section of the
intestine inside an adjoining section. Intussusception
can be caused by small intestinal polyps.
Mucosal—Refers to tissues that produce mucus,
such as the digestive, genital and urinary tracts.
Neoplasm—A new growth of abnormal tissue.
Peristalsis—The rhythmic contractions of muscular
tubes like the intestines that carry the contents
along the tube.
Sigmoid—The S-shaped curve of the large intestine
where the colon joins the rectum.

Patients with hereditary disorders associated with
polyps must undergo total colectomy early in adult
life. All children of parents with these disorders should
be screened early in adulthood, because half of them
will have the same disease. For the bulk of the population, increased dietary fiber and decreased animal fat
are the best preventives known at present. For the
occasional intestinal polyp that arises in spite of
good dietary habits, routine screening should prevent
it from becoming cancerous.
Resources
BOOKS

Silverstein, Fred E. ‘‘Gastrointestinal Endoscopy.’’ In
Harrison’s Principles of Internal Medicine, edited
Anthony S. Fauci, et al. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Intestinal strangulation see Intestinal
obstructions
cramping abdominal pain with nausea and vomiting. As
colon polyps evolve into cancers, they begin to produce
symptoms that include bleeding and altered bowel
habits.

Diagnosis
Routine screening for bowel cancer is recommended for everyone over the age of 40. Screening
may be as simple as testing the stool for blood or as
elaborate as colonoscopy. Colonoscopy is a procedure
in which the doctor threads an instrument called a
colonoscope up through the entire large bowel. Most
polyps are in the lower segment of the colon, called the
sigmoid colon. These polyps can be seen with a shorter
scope called a sigmoidoscope. X ray imaging can also
used to look for polyps. For x rays, the colon is first
filled with barium, which is a white substance that
shows up as a shadowed area on the film. The colon
can also be filled with barium and air, which is called a
double contrast study.
Because polyps take about five years to turn into
cancers, routine examinations are recommended every
three years.

Treatment
All polyps should be removed as preventive care.
Most of them can be taken out through a colonoscope.
Complications like obstruction and intussusception
are surgical emergencies.
2054

Intoxication confusional state see Delirium
Intracavity therapy see Radioactive implants
Intracranial abscess see Brain abscess
Intrapartum monitoring see Electronic fetal
monitoring
Intrauterine device see IUD

Intrauterine growth
retardation
Definition
Intrauterine growth retardation (IUGR) occurs
when the unborn baby is at or below the 10th weight
percentile for his or her age (in weeks).

Description
There are standards or averages in weight for
unborn babies according their age in weeks. When
the baby’s weight is at or below the 10th percentile
for his or her age, it is called intrauterine growth
retardation or fetal growth restriction. These babies
are smaller than they should be for their age. How
much a baby weighs at birth depends not only on
how many weeks old it is, but the rate at which it has
GALE ENCYCLOPEDIA OF MEDICINE

IUGR is usually classified as symmetrical or
asymmetrical. In symmetrical IUGR, the baby’s
head and body are proportionately small. In asymmetrical IUGR, the baby’s brain is abnormally large
when compared to the liver. In a normal infant, the
brain weighs about three times more than the liver. In
asymmetrical IUGR, the brain can weigh five or six
times more than the liver.

Causes and symptoms
Doctors think that the two types of IUGR may be
linked to the time during development that the
problem occurs. Symmetrical IUGR may occur when
the unborn baby experiences a problem during early
development. Asymmetrical IUGR may occur when
the unborn baby experiences a problem during later
development. While not true for all asymmetrical
cases, doctors think that sometimes the placenta may
allow the brain to get more oxygen and nutrition while
the liver gets less.
There are many IUGR risk factors involving the
mother and the baby. A mother is at risk for having a
growth restricted infant if she:


Has had a previous baby who suffered from IUGR



Is small in size



Has poor weight gain and nutrition during pregnancy



Is socially deprived



Uses substances (like tobacco, narcotics, alcohol)
that can cause abnormal development or birth defects



Has a vascular disease (like preeclampsia)



Has chronic kidney disease



Has a low total blood volume during early pregnancy



Is pregnant with more than one baby



Has an antibody problem that can make successful
pregnancy difficult (antiphospholipid antibody
syndrome).

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Preeclampsia—Hypertension (high blood pressure)
during pregnancy.

Additionally, an unborn baby may suffer from
IUGR if it has:


Exposure to an infection, including German measles
(rubella), cytomegalovirus, tuberculosis, syphilis, or
toxoplasmosis



A birth defect (like a severe cardiovascular defect)



A chromosome defect, especially trisomy 18
(Edwards’ syndrome)



A primary disorder of bone or cartilage



A chronic lack of oxygen during development
(hypoxia)



Placenta or umbilical cord defects



Developed outside of the uterus.

Diagnosis
IUGR can be difficult to diagnose and in many
cases doctors are not able to make an exact diagnosis
until the baby is born. A mother who has had a growth
restricted baby is at risk of having another during a
later pregnancy. Such mothers are closely monitored
during pregnancy. The length in weeks of the pregnancy must be carefully determined so that the doctor
will know if development and weight gain are appropriate. Checking the mother’s weight and abdomen
measurements can help diagnose cases when there
are no other risk factors present. Measuring the girth
of the abdomen is often used as a tool for diagnosing
IUGR. During pregnancy, the healthcare provider
will use a tape measure to record the height of the
upper portion of the uterus (the uterine fundal height).
As the pregnancy continues and the baby grows, the
uterus stretches upward in the direction of the
mother’s head. Between 18 and 30 weeks of gestation,
the uterine fundal height (in cm.) equals the weeks
of gestation. If the uterine fundal height is more than
2–3 cm below normal, then IUGR is suspected.
Ultrasound is used to evaluate the growth of the
baby. Usually, IUGR is diagnosed after week 32 of
pregnancy. This is during the phase of rapid growth
when the baby should be gaining more weight. IUGR
caused by genetic factors or infection may sometimes
be detected earlier.
2055

Intrauterine growth retardation

grown. This growth process is complex and delicate.
There are three phases associated with the development of the baby. During the first phase, cells multiply
in the baby’s organs. This occurs from the beginning
of development through the early part of the fourth
month. During the second phase, cells continue to
multiply and the organs grow. In the third phase
(after 32 weeks of development), growth occurs
quickly and the baby may gain as much as 7 ounces
per week. If the delicate process of development and
weight gain is disturbed or interrupted, the baby can
suffer from restricted growth.

Intravenous rehydration

Treatment
There is no treatment that improves fetal growth,
but IUGR babies who are at or near term have the best
outcome if delivered promptly. If IUGR is caused by a
problem with the placenta and the baby is otherwise
healthy, early diagnosis and treatment of the problem
may reduce the chance of a serious outcome.

KEY TERMS
Intravenous—Into a vein; a needle is inserted into a
vein in the back of the hand, inside the elbow, or
some other location on the body. Fluids, nutrients,
and drugs can be injected.

Prognosis
Babies who suffer from IUGR are at an increased
risk for death, low blood sugar (hypoglycemia), low
body temperature (hypothermia), and abnormal development of the nervous system. These risks increase
with the severity of the growth restriction. The growth
that occurs after birth cannot be predicted with
certainty based on the size of the baby when it is
born. Infants with asymmetrical IUGR are more
likely to catch up in growth after birth than are infants
who suffer from prolonged symmetrical IUGR.
However, as of 1998, doctors cannot reliably predict
an infant’s future progress. Each case is unique. Some
infants who have IUGR will develop normally, while
others will have complications of the nervous system
or intellectual problems like learning disorders. If
IUGR is related to a disease or a genetic defect, the
future of the infant is related to the severity and the
nature of that disorder.
Resources

Purpose
Fever, vomiting, and diarrhea can cause a person
to become dehydrated fairly quickly. Infants and
children are especially vulnerable to dehydration.
Patients can become dehydrated due to an illness,
surgery, or accident. Athletes who have overexerted
themselves may also require rehydration with IV
fluids. An IV for rehydration can be used for several
hours to several days, and is generally used if a patient
cannot drink fluids.

Precautions
Patients receiving IV therapy need to be monitored to ensure that the IV solutions are providing
the correct amounts of fluids and minerals needed.
People with kidney and heart disease are at increased
risk for overhydration, so they must be carefully
monitored when receiving IV therapy.

BOOKS

Cunningham, F. Gary, et al. Williams Obstetrics. 20th ed.
Stamford: Appleton & Lange, 1997.

Linda Jones

Intravenous nutrition see Nutrition through
an intravenous line
Intravenous pyelography see Intravenous
urography

Intravenous rehydration
Definition
Sterile water solutions containing small amounts
of salt or sugar, are injected into the body through
a tube attached to a needle which is inserted into a
vein.
2056

Description
Basic IV solutions are sterile water with small
amounts of sodium (salt) or dextrose (sugar) supplied
in bottles or thick plastic bags that can hang on a stand
mounted next to the patient’s bed. Additional minerals like potassium and calcium, vitamins, or drugs can
be added to the IV solution by injecting them into the
bottle or bag with a needle.

Preparation
A doctor orders the IV solution and any additional nutrients or drugs to be added to it. The doctor
also specifies the rate at which the IV will be infused.
The IV solutions are prepared under the supervision of
a doctor, pharmacist, or nurse, using sanitary techniques that prevent bacterial contamination. Just like a
prescription, the IV is clearly labeled to show its
contents and the amounts of any additives. The skin
around the area where the needle is inserted is cleaned
and disinfected. Once the needle is in place, it will be
taped to the skin to prevent it from dislodging.
GALE ENCYCLOPEDIA OF MEDICINE

into the lower end of the system, therefore flowing
backward or ‘‘retrograde.’’ Retrograde pyelography
is better able to define problems in the lower parts of
the system and is the only way to get x rays if the
kidneys are not working well.

Patients need to take fluids by mouth before an IV
solution is discontinued. After the IV needle is
removed, the site should be inspected for any signs of
bleeding or infection.


Risks
There is a small risk of infection at the injection
site. It is possible that the IV solution may not provide
all of the nutrients needed, leading to a deficiency or
an imbalance. If the needle becomes dislodged, it is
possible that the solution may flow into tissues around
the injection site rather than into the vein.
Resources

Nephrotomography is somewhat different in that the
x rays are taken by a moving x ray source onto a film
moving in the opposite direction. By accurately coordinating the movement, all but a single plane of
tissue is blurred, and that plane is seen without overlying shadows.

Every method available gives good pictures of this
system, and the question becomes one of choosing
among many excellent alternatives. Each condition
has special requirements, while each technique has
distinctive benefits and drawbacks.

OTHER

Martinez-Bianchi, Viviana, Michelle Rejman-Peterson, and
Mark A. Graber. ‘‘Pediatrics: Vomiting, Diarrhea, and
Dehydration.’’ Family Practice Handbook. University
of Iowa. <http://www.vh.org/Providers/ClinRef/
FPHandbook/Chapter10/17-10.html>.
Toth, Peter P. ‘‘Gastoenterology: Acute Diarrhea.’’ Family
Practice Handbook. University of Iowa.
<http://www.vh.org/Providers/ClinRef/
FPHandbook/Chapter04/01-4.html>.



Nuclear scans rely on the radiation given off by certain atoms. Chemicals containing such atoms are
injected into the bloodstream. They reach the kidneys,
where images are constructed by measuring the radiation emitted. The radiation is no more dangerous than
standard x rays. The images require considerable
training to interpret, but unique information is often
available using this technology. Different chemicals
can concentrate the radiation in different types of
tissue. This technique may require several days for
the chemical to concentrate at its destination. It also
requires a special detector to create the image.



Ultrasound is a quick, safe, simple, and inexpensive
way to obtain views of internal organs. Although less
detailed than other methods, it may be sufficient.



Retrograde pyelography is better able to define
problems in the lower parts of the system and is the
only way to get x rays if the kidneys are not working
well. Dye is usually injected through an instrument
(cystoscope) passed into the bladder through the
urethra.



Computed tomography scans (CT or CAT scanning)
uses the same kind of radiation used in x rays, but it
collects information by computer in such a way that
three dimensional images can be constructed, eliminating interference from nearby structures. CT scanning requires a special apparatus.



Magnetic resonance imaging (MRI) uses magnetic
fields and radio frequency signals, instead of ionizing
radiation, to create computerized images. This form
of energy is entirely safe as long as the patient has no
metal on board. The technique is far more versatile
than CT scanning. MRI requires special apparatus
and, because of the powerful magnets needed, even a
special building all by itself. It is quite expensive.

Altha Roberts Edgren

Intravenous urography
Definition
Intravenous urography is a test which x rays the
urinary system using intravenous dye for diagnostic
purposes.
Of the many ways to obtain images of the urinary
system, the intravenous injection of a contrast agent
has been traditionally considered the best. The kidneys
excrete the dye into the urine. X rays can then create
pictures of every structure through which the urine
passes.
The procedure has several variations and many
names.


Intravenous pyelography (IVP).



Urography.



Pyelography.



Antegrade pyelography differentiates this procedure
from ‘‘retrograde pyelography,’’ which injects dye

GALE ENCYCLOPEDIA OF MEDICINE

2057

Intravenous urography

Aftercare

Intussusception

Purpose
Most diseases of the kidneys, ureters, and bladder
will yield information to this procedure, which actually has two phases. First, it requires a functioning
kidney to filter the dye out of the blood into the
urine. The time required for the dye to appear on
x rays correlates accurately with kidney function. The
second phase gives detailed anatomical images of the
urinary tract. Within the first few minutes the dye
‘‘lights up’’ the kidneys, a phase called the nephrogram.
Subsequent pictures follow the dye down the ureters
and into the bladder. A final film taken after urinating
reveals how well the bladder empties.
IVPs are most often done to assess structural
abnormalities or obstruction to urine flow. If kidney
function is at issue, more films are taken sooner to
catch the earliest phase of the process.


Stones, tumors and congenital malformations
account for many of the findings.



Kidney cysts and cancers can be seen.



Displacement of a kidney or ureter suggests a spaceoccupying lesion like a cancer pushing it out of
the way.



Bad valves where the ureters enter the bladder will
often show up.





Bladder cancers and other abnormalities are often
outlined by the dye in the bladder.
An enlarged prostate gland will show up as incomplete bladder emptying and a bump at the bottom of
the bladder.

KEY TERMS
Contrast agent—Any substance that causes shadows on x rays, also known as contrast dye or
medium.
Intravenous—Into a vein.

Preparation
Emptying the bowel with laxatives or enemas
prevents bowel shadows from obscuring the details
of the urinary system. An empty stomach prevents
the complications of vomiting, a rare effect of the
contrast agent. Therefore, the night before the IVP
the patient will be asked to evacuate the bowels and
to drink sparingly.

Risks
Allergy to the contrast agent is the only risk.
Anyone with a possible iodine allergy or a previous
reaction to x ray dye must be particularly careful to
inform the x ray personnel.
Resources
BOOKS

Merrill, Vinta. Atlas of Roentgenographic Positions and
Standard Radiologic Procedures. Saint Louis: The
C.V. Mosby Co., 1975.

J. Ricker Polsdorfer, MD

Precautions
The only serious complication of an IVP is allergy
to the iodine-containing dye that is used. Such an
allergy is rare, but it can be dramatic and even lethal.
Emergency measures taken immediately are usually
effective.

Description
IVPs are usually done in the morning. In the x ray
suite, the patient will undress and lie down. There are
two methods of injecting the dye. An intravenous line
can be established, through which the dye will be consistently fed through the body during the procedure.
The other method is to give the dye all at once through
a needle that is immediately withdrawn. X rays are
taken until the dye has reached the bladder, an interval
of half an hour or less. The patient will be asked to
empty the bladder before one last x ray.
2058

Intussusception
Definition
Intussusception is the enfolding of one segment of
the intestine within another. It is characterized and
initially presents with recurring attacks of cramping
abdominal pain that gradually become more painful.

Description
Intussusception occurs when part of the bowel or
intestine is wrapped around itself producing a masslike object on the right side of the abdomen during
palpation (a procedure used during a physical examination, when the examiner touches the abdomen with
GALE ENCYCLOPEDIA OF MEDICINE

Physical examination and palpation usually
reveal a sausage shaped mass of enfolded bowel in
the right upper mid portion of the abdomen. Within
a few hours approximately 50% of cases have bloody,
mucus filled bowel movements. At about this time the
child is visibly very ill with fever, tenderness, and distended abdomen. Intussusception is the most frequent
cause of intestinal obstruction during the first two
years of life and commonly affects children between
three to 12 months of age. The disease is three times
more common in males than in females. In about 85%
of cases the cause is idiopathic (meaning unknown).
The remaining 15% of cases can be caused by a variety
of other diseases such as tumors of the lymph nodes
(lymphoma), fat tumors (lipomas), foreign bodies/
objects, or from infections that mobilize immune
cells to the area causing and an inflammatory reaction
and intestinal blockage. Most cases of intussusception
do not strangulate the affected bowel within the first
24 hours. If the disease is not treated after this time, the
possibility of intestinal gangrene, shock, and death
increases.

Causes and symptoms
The major symptom of intussusception is when a
healthy child suddenly and without warning experiences severe abdominal pain that subsides and
usually results in continuation of normal activities
such as playing. The duration of the painful attacks
increases as the hours go by. Usually, the child
develops nausea, vomiting, and diarrhea soon afterwards in about 90% of all cases. The child becomes
weak, exhausted, and develops a fever. The affected
child may also expel bloody, mucus-like bowel
movements. These blood filled bowel movements
are usually due to impaired blood flow to the
obstructed area. During palpation there may be a
sausage-shaped mass located on the upper right mid
portion of the abdomen. If the disease progresses and
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Barium—A chemical used in certain radiological
studies to enhance visualization of anatomical
structures.
Obstruction—A blockage that prevents movement.

is undetected, the child may develop necrosis death of
cells within the affected area. Additionally, there may
be perforation or hole in the intussusception bowel
that can cause a life threatening infection in the
peritoneum (a layer of tissue that protects the
organs and intestines within the abdominal cavity).
This infection of the peritoneum is called peritonitis.
Some patients may exhibit altered states of
consciousness or seizures.

Diagnosis
A presumed diagnosis can be made by history
alone. If the clinician suspect’s intussusception x-ray
films should be performed, which may reveal a mass in
the right upper mid abdominal region. Two classical
clinical signs are mucus-blood filled stools and a
‘‘coiled string’’ appearance in the affected bowel as
visualized during an x ray with a barium enema.
Blood chemistry analysis is not specific for intussusception. Depending on vomiting and blood loss
through the stools, blood chemistry may reflect signs
of dehydration and anemia.

Treatment
Treating intussusception by reduction (alleviating the source of blockage) is an emergency procedure. The barium examination is not only the
diagnostic tool of choice, but also frequently curative. Infusion by gravity from a catheter placed in the
rectum will tend to relieve pressure buildup. If this
does not relieve the area, then air can be pumped into
the colon to clear blockage. If these procedures are
unsuccessful then surgery is required. Approximately
25% of affected children require surgical intervention. Surgery in the affected bowel is advantageous
since the actual cause can be removed, and the
procedure decreases the possibility of recurrences.
In general without surgical correction of the affected
bowel, there is a 5–10% chance of recurrence.
Recurrence usually appears within the first 24 to 48
hours after barium procedure.
2059

Intussusception

his/her hand, usually feeling for mass, pain, or discomfort). The number of new cases of intussuscetion
is approximately 1.5 to four cases per 1,000 live births.
The onset of abdominal pain is usually abrupt and
severe. Just as fast as the onset of pain appears, it
disappears and the child resumes activity normally.
This process of sudden severe abdominal pain appearing out of the blue then disappearing is repeated with
duration of painful attacks. The pain usually increases
after approximately five hours of recurrent cycles of
severe abdominal pain followed by relaxation.
Vomiting and diarrhea occur in about 90% of cases
with six to 12 hours after initial onset of symptoms.

Ipecac

Prognosis
The outcome of intussusception depends on the
duration of symptoms before treatment initiation.
Most infants will recover if treatment is initiated
within the first 24 hours. Untreated intussusception
is almost always fatal. Overall even with treatment,
approximately 1–2% of affected children will die.

Prevention
Prevention of death can be accomplished with
immediate medical care, within the first 24 hours.
Once intussusception is suspected, emergency measures should be initiated. Untreated intussusception
is almost always fatal. There is an increased chance
for death if the disorder is not treated within
48 hours.

however, doctors are discouraging the use of ipecac in
emergency treatment of poisoning. The reason for this
change in practice is that ipecac has not been shown to
be more effective than activated charcoal or gastric
lavage; in addition, its use may delay the administration
of these other methods of treatment. In 2004 the
American College of Toxicology updated a 1997 position paper on the use of syrup of ipecac to treat poisoning with the following statement: ‘‘There is no evidence
from clinical studies that ipecac improves the outcome
of poisoned patients and its routine administration in
the emergency department should be abandoned.’’
Ipecac should never be used to induce vomiting if
the poison is one of the following:


strychnine



alkalis (lye)



strong acids



kerosene

Behrman, Richard E., et al, editors. Nelson Textbook of
Pediatrics. 16th ed. W. B. Saunders Company, 2000.
Townsend, Courtney M., et al. Sabiston Textbook of
Surgery. 16th ed. W. B. Saunders Company, 2001.



fuel oil



gasoline



coal oil

OTHER



paint thinner

University of Maryland. 2001. <http://www.umm.edu>.



cleaning fluid

Resources
BOOKS

Laith Farid Gulli, M.D.

Intussusception see Intestinal obstructions
Iodine see Antiseptics
Iodine uptake test see Thyroid nuclear
medicine scan

Ipecac
Definition
Ipecac is a medicine commonly used to induce
vomiting in cases of accidental poisoning. It is also a
homeopathic remedy.

Purpose
Treatment of poisoning
At one time, standard medical practice recommended syrup of ipecac to cause vomiting in cases of
poisoning in order to remove the toxic substance from
the stomach before absorption occurs. More recently,
2060

In cases of poisoning, it is always best to contact a
local poison control center, local hospital emergency
room, or the family doctor for instructions before
using syrup of ipecac.
Ipecac’s reputation for inducing vomiting has
encouraged some bulimics to take it on a regular
basis in order to purge the contents of the stomach
after an eating binge. This misuse of ipecac is extremely dangerous; it can cause heart problems, tears in
the esophagus or stomach lining, vomiting blood, seizures, or even death.
Homeopathy
The homeopathic remedy made from ipecac is
called Ipecacuanha. Homeopathic preparations are
given for a reason completely opposite from that of
standard allopathic treatment. In homeopathy, ipecac
is given to stop vomiting rather than to induce it.
According to Hahnemann’s law of similars, a
substance that would cause vomiting in large doses
when given to a healthy person will stimulate a sick
person’s natural defenses when given in extremely
dilute and carefully prepared doses. Ipecacuanha is a
favorite homeopathic remedy for morning sickness
associated with pregnancy. It is also given to stop nausea that is not relieved by vomiting; when the vomitus is
GALE ENCYCLOPEDIA OF MEDICINE

Ipecac plant (Cephaelis ipecacuanha). (PlantaPhile Germany.
Reproduced by permission.)

Ipecacuanha is a homeopathic remedy made from
ipecac by a process of dilution and succussion
(shaking). In contrast to syrup of ipecac, it is given to
relieve vomiting.

Recommended dosage
slimy and white; when there is gagging and heavy salivation; when the tongue is clean despite the patient’s
feelings of nausea; and when the patient is not thirsty.
The nausea may be accompanied by a headache, cough,
or heavy menstrual bleeding. The modalities (circumstances) that suggest Ipecacuanha as the appropriate
homeopathic remedy is that the patient feels worse
lying down; in dry weather; in winter; and when
exercising or moving about.
A homeopathic practitioner would not necessarily
prescribe ipecac for all cases of nausea. Arsenicum
would be given when the nausea is caused by food
poisoning and accompanied by strong thirst, Nux
vomica when the nausea is the result of overindulgence
in food or alcohol and accompanied by gas or heartburn. A sick child might be given Pulsatilla, particularly if rich foods have been eaten.
On the other hand, a homeopathic practitioner
may prescribe ipecac for any of the following conditions that are not related to nausea and vomiting.


Nosebleeds producing bright red blood.



Dental bleeding.



Diarrhea with cramping abdominal pain. The stools
are green with froth or foam.



Asthma of sudden onset. The patient has to sit up in
order to breathe, but cannot bring up any mucus in
spite of violent coughing.



Hoarseness or loss of voice following a cold.



Physical or mental exhaustion.

Description
The medicinal effects of ipecac were recognized
centuries ago by the Portuguese who settled in South
GALE ENCYCLOPEDIA OF MEDICINE

Syrup of ipecac
Syrup of ipecac is made from the dried roots and
rhizomes (underground stems) of Cephaelis ipecacuanha. It is available over the counter in 0.5–1 oz
bottles. Larger bottles require a doctor’s prescription. The dosage for infants under 6 months old
should be prescribed by the family doctor or poison
control center. For children six months to one year,
the usual dose is 5–10 ml or 1–2 tsp. One-half or one
full glass (4–8 oz) of water should be taken immediately before or after the dose. The dose may be
repeated once after 20–30 minutes if vomiting does
not occur. For children one to 12 years of age, the
usual dose is 15 ml (1 tbsp) to be taken with one full
glass (8 oz) of water. Adults and teenagers should
take 15–30 ml of ipecac with at least 1 full glass of
water. Syrup of ipecac should not be taken with milk
or soda drinks as these foods may prevent it from
working properly. If vomiting does not occur within
20–30 minutes after the first dose, a second dose may
be needed. If the second dose fails to induce vomiting,
the patient should be taken to a hospital emergency
room.
If both activated charcoal and syrup of ipecac are
recommended to treat poison, ipecac must be used
first. Activated charcoal should not be taken until
30 minutes after taking syrup of ipecac, or until the
vomiting caused by ipecac stops.
Homeopathic preparations
Ipecacuanha is available as an over-the-counter
remedy in 30x potency. This is a decimal potency,
which means that one part of ipecac has been mixed
with nine parts of alcohol or water; 30x means that this
decimal dilution has been repeated 30 times. The dilute
2061

Ipecac

America. They found a plant that can make people
vomit and appropriately named it Caephalis ipecacuanha, meaning sick-making plant. Syrup of ipecac
is now considered the safest drug to treat poisoning
and is often the most effective. There are different
types of ipecac preparations that vary greatly in
strength. Syrup of ipecac is best for use at home to
treat accidental poisoning. Ipecac fluid extract and
ipecac tincture should be avoided as they are much
stronger compounds and can be toxic.

Ipecac

solution of ipecac is then added to sugar tablets so that
the remedy can be taken in tablet form.

KEY TERMS
Bulimia nervosa—An eating disorder characterized by episodic binge eating followed by selfinduced vomiting or laxative abuse.
Cephaeline—A chemical compound found in ipecac that irritates the stomach lining and triggers the
vomiting reflex.

Precautions
Syrup of ipecac
For inducing vomiting in cases of accidental
poisoning, only the syrup form of ipecac should be
used. Syrup of ipecac should not be mixed with milk
or carbonated drinks as they may prevent vomiting.

Fluid extract—A concentrated preparation of a
drug.

Syrup of ipecac should not be used in the following situations (contact poison control center or family
doctor for alternative treatments).


Poisoning caused by strychnine; sustained-release
theophylline; such corrosive substances as strong
alkalis (lye); strong acids (such as toilet bowl cleaner); and such petroleum products as kerosene, gasoline, coal oil, fuel oil, paint thinner, or cleaning
fluids.



Overdoses of medications given for depression.



Excessive vomiting.



A serious heart condition.



Timing. Do not give ipecac more than 4–6 hours
after the poison was ingested.



Pregnancy.



Very young children (less than six months old).
Infants and very young children may choke on their
own vomit or get vomit into their lungs.



Drowsy or unconscious patients.



Seizures.

Law of similars—A principle of homeopathic treatment according to which substances that cause
specific symptoms in healthy people are given to
sick people with similar symptoms.
Modality—A factor or circumstance that makes a
patient’s symptoms better or worse. Modalities
include such factors as time of day, room temperature, the patient’s level of activity, sleep patterns, etc.
Tincture—An alcoholic solution of a chemical or
drug.



Muscle stiffness.



Severe heart problems often occur in cases of ipecac
abuse. Because ipecac stays in the body for a long
time, damage to the heart frequently occurs in
persons who repeatedly take ipecac to induce
vomiting.



Seizures. These are most likely to occur in patients
who accidentally swallow ipecac or in ipecac
abusers.



Death. Deaths have been reported due to ipecac
abuse in bulimic persons.

Homeopathic preparations
Ipecacuanha should not be given after Arsenicum
or Tabac because these remedies will counteract it.

Side effects
The following side effects have been associated
with the use of syrup of ipecac:


Loose bowel movements.



Diarrhea.



Fast irregular heartbeat.



Inhaling or choking on vomit.



Stomach cramps or pains.



Coughing.



Weakness.



Aching.

2062

Homeopathic Ipecacuanha has been highly
diluted and is relatively nontoxic.

Interactions
If used to induce vomiting, ipecac should not be
given together with other drugs because it can decrease
their effectiveness and increase their toxicity. If both
syrup of ipecac and activated charcoal are needed to
treat suspected poisons, ipecac should be given first.
Activated charcoal should not be given until vomiting
induced by ipecac has stopped. Carbonated beverages
should also be avoided because they can cause
the stomach to swell. The person should lie on the
stomach or side in case vomiting occurs.
GALE ENCYCLOPEDIA OF MEDICINE

Resources

characterized by the production of small red blood
cells. When examined under a microscope, the red
blood cells also appear pale or light colored. For this
reason, the anemia that occurs with iron deficiency is
also called hypochronic microcytic anemia.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Bulimia Nervosa.’’ Section 15, Chapter 196. In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Poisoning.’’ Section 23, Chapter 307. In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PDR Nurse’s Drug Handbook. Montvale, NJ: Delmar
Publishers, 2000.
PERIODICALS

‘‘Position Paper: Ipecac Syrup.’’ Journal of Toxicology:
Clinical Toxicology 42 (February 2004): 133–143.

Description
Iron deficiency anemia is the most common type
of anemia throughout the world. In the United States,
iron deficiency anemia occurs to a lesser extent than in
developing countries because of the higher consumption of red meat and the practice of food fortification
(addition of iron to foods by the manufacturer).
Anemia in the United States is caused by a variety of
sources, including excessive losses of iron in menstrual
fluids and excessive bleeding in the gastrointestinal
tract. In developing countries located in tropical climates, the most common cause of iron deficiency anemia is infestation with hookworm.

ORGANIZATIONS

American College of Toxicology (ACT). 9650 Rockville
Pike, Bethesda, MD 20814. (301) 634-7840. Fax: (301)
634-7852. <http://www.actox.org>.
American Foundation for Homeopathy. 1508 S. Garfield,
Alhambra, CA 91801.
Homeopathic Educational Services. 2124B Kittredge
St. Berkeley, CA 94704. (510) 649-0294. Fax: (510)
649-1955.

Rebecca J. Frey, PhD

Ipratropium see Bronchodilators
I.Q. tests see Stanford-Binet intelligence
scales; Wechsler intelligence test
Iridocyclitis see Uveitis
Iritis see Uveitis
Iron-binding capacity test see Iron tests
Iron-utilization anemias see Sideroblastic
anemia

Iron deficiency anemia
Definition
Anemia can be caused by iron deficiency, folate
deficiency, vitamin B12 deficiency, and other causes.
The term iron deficiency anemia means anemia that is
due to iron deficiency. Iron deficiency anemia is
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Infancy is a period of increased risk for iron deficiency. The human infant is born with a built-in supply
of iron, which can be tapped during periods of drinking low-iron milk or formula. Both human milk and
cow milk contain rather low levels of iron (0.5–1.0 mg
iron/liter). However, the iron in human milk is about
50% absorbed by the infant, while the iron of cow milk
is only 10% absorbed. During the first six months
of life, growth of the infant is made possible by the
milk in the diet and by the infant’s built-in supply.
However, premature infants have a lower supply of
iron and, for this reason, it is recommended that preterm infants (beginning at 2 months of age) be given
oral supplements of 7 mg iron/day, as ferrous sulfate.
Iron deficiency can be provoked where infants are fed
formulas that are based on unfortified cow milk. For
example, unfortified cow milk is given free of charge to
mothers in Chile. This practice has the fortunate result
of preventing general malnutrition, but the unfortunate result of allowing the development of mild iron
deficiency.
The normal rate of blood loss in the feces is 0.5–
1.0 ml per day. These losses can increase with colorectal
cancer. About 60% of colorectal cancers result in
further blood losses, where the extent of blood loss is
2-10 ml/day. Cancer of the colon and rectum can provoke losses of blood, resulting in iron deficiency anemia. The fecal blood test is widely used to screen for the
presence of cancer of the colon or rectum. In the
absence of testing, colorectal cancer may be first
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Iron deficiency anemia

Homeopathic Ipecacuanha is considered complementary to Arnica and Cuprum. It is counteracted by
Arsenicum and Tabac.

Iron deficiency anemia

detected because of the resulting iron deficiency
anemia.
Infection with hookworm can provoke iron deficiency and iron deficiency anemia. The hookworm is a
parasitic worm. It thrives in warm climates, including
in the southern United States. The hookworm enters
the body through the skin, as through bare feet. The
hookworm then migrates to the small intestines where
it attaches itself to the villi (small sausage-shaped
structures in the intestines that are used for the absorption of all nutrients). The hookworm provokes
damage to the villi, resulting in blood loss, and they
produce anti-coagulants which promote continued
bleeding. Each worm can provoke the loss of up to
0.25 ml of blood per day.
Bleeding and blood losses through gastrointestinal tract can be provoked by colorectal cancer
and hookworms, as mentioned above, but also by
hemorrhoids, anal fissures, irritable bowel syndrome,
aspirin-induced bleeding, blood clotting disorders,
and diverticulosis (a condition caused by an abnormal
opening from the intestine or bladder). Several genetic
diseases exist which lead to bleeding diorders, and
these include hemophilia A, hemophilia B, and von
Willebrand’s disease. Of these, only von Willebrand’s
disease leads to gastrointestinal bleeding.
The symptoms of iron deficiency anemia include
weakness and fatigue. These symptoms result because
of the lack of function of the red blood cells, and the
reduced ability of the red blood cells to carry iron to
exercising muscles. Iron deficiency can also affect
other tissues, including the tongue and fingernails.
Prolonged iron deficiency can result in changes of
the tongue, and it may become smooth, shiny, and
reddened. This condition is called glossitis. The fingernails may grow abnormally, and acquire a spoonshaped appearance.
Decreased iron intake is a contributing factor
in iron deficiency and iron deficiency anemia. The
iron content of cabbage, for example, is about
1.6 mg/kg food, while that of spinach (33 mg/kg),
lima beans (15 mg/kg), potato (14 mg/kg), tomato
(3 mg/kg), apples (1.5 mg/kg), raisins (20 mg/kg),
whole wheat bread (43 mg/kg), eggs (20 mg/kg),
canned tuna (13 mg/kg), chicken (11 mg/kg), beef
(28 mg/kg), corn oil (0.6 mg/kg), and peanut butter
(6.0 mg/kg), are indicated. One can see that apples,
tomatoes, and vegetable oil are relatively low in
iron, while whole wheat bread and beef are relatively high in iron. The assessment of whether a
food is low or high in iron can also be made by
comparing the amount of that food eaten per day
2064

with the recommended dietary allowance (RDA)
for iron. The RDA for iron for the adult male
is 10 mg/day, while that for the adult woman is
15 mg/day. The RDA during pregnancy is 30 mg/
day. The RDA for infants of 0–0.5 years of age is
6 mg/day, while that for infants of 0.5–1.0 years of
age is 10 mg/day. The RDA values are based on
the assumption that the consumer eats a mixture of
plant and animal foods.
The above list of iron values alone may be deceptive, since the availability of iron in fruits, vegetables,
and grains is very low, while that the availability from
meat is much higher. The availability of iron in plants
ranges from only 1–10%, while that in meat, fish,
chicken, and liver is 20–30%. The term availability
means the percent of dietary iron that is absorbed via
the gastrointestinal tract to the bloodstream. Nonabsorbed iron is lost in the feces.
Interactions between various foods can influence
the absorption of dietary iron. Vitamin C can increase
the absorption of dietary iron. Orange juice is a rich
source of vitamin C. Thus, if a plant food, such as rice,
is consumed with orange juice, then the orange juice
can enhance the absorption of the iron of the rice.
Vitamin C is also added to infant formulas, and the
increased use of formulas fortified with both iron and
vitamin C have led to a marked decline in anemia in
infants and young children in the United States
(Dallman, 1989). In contrast, if rice is consumed with
tea, certain chemicals in the tea (tannins) can reduce
the absorption of the iron. Phytic acid is a chemical
that naturally occurs in legumes, cereals, and nuts.
Phytic acid, which can account for 1–5% of the weight
of these foods, is a potent inhibitor of iron absorption.
The increased availability of the iron in meat products
is partly due to the fact that heme-iron is absorbed to a
greater extent than free iron salts, and to a greater
extent than iron in the phytic acid/iron complex.
Nearly all of the iron in plants is nonheme-iron.
Much of the iron in meat is nonheme-iron as well.
The nonheme-iron in meat, fish, chicken and liver
may be about 20% available. The heme-iron of meat
may be close to 30% available. The most available
source of iron is human milk (50% availability).

Diagnosis
Iron deficiency anemia in infants is defined as a
hemoglobin level below 109 mg/ml of whole blood,
and a hematocrit of under 33%. Anemia in adult
males is defined as a hemoglobin under 130 mg/ml
and a hematocrit of under 38%. Anemia in adult
females is defined as hemoglobin under 120 mg/ml
GALE ENCYCLOPEDIA OF MEDICINE

When an abnormally high presence of blood is
found in the feces during a fecal occult blood test, the
physician needs to examine the gastrointestinal tract
to determine the cause of bleeding. Here, the diagnosis
for iron deficiency anemia includes the examination
using a sigmoidoscope. The sigmoidoscope is an
instrument that consists of a flexible tube that permits
examination of the colon to a distance of 60 cm. A
barium enema, with an x ray, may also be used to
detect abnormalities that can cause bleeding.
The diagnosis of iron deficiency anemia should
include a test for oral iron absorption, where evidence
suggests that oral iron supplements fail in treating
anemia. The oral iron absorption test is conducted by
eating 64 mg iron (325 mg ferrous sulfate) in a single
dose. Blood samples are then taken after 2 hours and 4
hours. The iron content of the blood serum is then
measured. The concentration of iron should rise by
an increment of about 22 micromolar, where iron
absorption is normal. Lesser increases in concentration
mean that iron absorption is abnormal, and that therapy should involve injections or infusions of iron.

KEY TERMS
Hematocrit—The proportion of whole blood in the
body, by volume, that is composed of red blood
cells.
Hemoglobin—Hemoglobin is an iron-containing
protein that resides within red blood cells.
Hemoglobin accounts for about 95% of the protein
in the red blood cell.
Protoporphyrin IX—Protoporphyrin IX is a protein.
The measurement of this protein is useful for the
assessment of iron status. Hemoglobin consists of a
complex of a protein plus heme. Heme consists of
iron plus protoporphyrin IX. Normally, during the
course of red blood cell formation, protoporphyrin
IX acquires iron, to generate heme, and the heme
becomes incorporated into hemoglobin. However,
in iron deficiency, protophoryrin IX builds up.
Recommended Dietary Allowance (RDA)—The
Recommended Dietary Allowances (RDAs) are
quantities of nutrients of the diet that are required to
maintain human health. RDAs are established by the
Food and Nutrition Board of the National Academy
of Sciences and may be revised every few years.

Treatment
Oral iron supplements (pills) may contain various
iron salts. These iron salts include ferrous sulfate, ferrous gluconate, or ferrous fumarate. Injections and
infusions of iron can be carried out with a preparation
called iron dextran. In patients with poor iron absorption (by the gut), therapy with injection or infusion is
preferable over oral supplements. Treatment of iron
deficiency anemia sometimes requires more than therapy with iron. Where iron deficiency was provoked by
hemorrhoids, surgery may prove essential to prevent
recurrent iron deficiency anemia. Where iron deficiency
is provoked by bleeding due to aspirin treatment,
aspirin should be discontinued. Where iron deficiency
is provoked by hookworm infections, therapy for this
parasite should be used, along with protection of the
feet by wearing shoes whenever walking in hookworminfested soil.

Prognosis
The prognosis for treating and curing iron
deficiency anemia is excellent. Perhaps the main problem is failure to take iron supplements. In cases of
pregnant women, the health care worker may recommend taking 100–200 mg iron/day. This dose is rather
GALE ENCYCLOPEDIA OF MEDICINE

high, and can lead to nausea, diarrhea, or abdominal
pain in 10–20% of women taking this dose. The reason
for using this high dose is to effect a rapid cure for
anemia, where the anemia is detected at a mid-point
during the pregnancy. The above problems of sideeffects and noncompliance can be avoided by taking
iron doses (100–200 mg) only once a week, where supplements are initiated some time prior to conception,
or continuously throughout the fertile period of life.
The problem of compliance is not an issue where infusions are used, however a fraction of patients treated
with iron infusions experience side effects, such as
flushing, headache, nausea, anaphylaxis, or seizures.
A number of studies have shown that iron deficiency
anemia in infancy can result in reduced intelligence,
where intelligence was measured in early childhood. It
is not certain if iron supplementation of children with
reduced intelligence, due to iron-deficiency anemia in
infancy, has any influence in allowing a ‘‘catch-up’’ in
intellectual development.

Prevention
In the healthy population, all of the mineral deficiencies can be prevented by the consumption of
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Iron deficiency anemia

and a hematocrit of under 32%. Anemia in pregnant
women is defined as hemoglobin of under 110 mg/ml
and hematocrit of under 31%.

Iron tests

inorganic nutrients at levels defined by the RDA. Iron
deficiency anemia in infants and young children can be
prevented by the use of fortified foods. Liquid cow
milk-based infant formulas are generally supplemented
with iron (12 mg/L). The iron in liquid formulas
is added as ferrous sulfate or ferrous gluconate.
Commercial infant cereals are also fortified with iron,
and here small particles of elemental iron are added.
The levels used are about 0.5 gram iron/kg dry cereal.
This amount of iron is about 10-fold greater than that
of the iron naturally present in the cereal.
Resources
PERIODICALS

Walter, T., P. Pino, F. Pizarro, and B. Lozoff. ‘‘Prevention
of Iron-deficiency Anemia: Comparison of Highand Low-iron Formulas in Term Healthy Infants
after Six Months of Life.’’ Journal of Pediatrics 132
(1998): 635-640.

Tom Brody, PhD

Iron overload see Hemochromatosis

Iron tests
Definition
Iron tests are a group of blood tests that are done
to evaluate the iron level in blood serum, the body’s
capacity to absorb iron, and the amount of iron
actually stored in the body. Iron is an essential trace
element; it is necessary for the formation of red blood
cells and certain enzymes. At the other extreme, high
levels of iron can be poisonous.

Purpose
There are four different types of tests that measure
the body’s iron levels and storage. They are called iron
level tests, total iron-binding capacity (TIBC) tests,
ferritin tests, and transferrin tests. These tests are
given for several reasons:


To help in the differential diagnosis of different types
of anemia.



To assess the severity of anemia and monitor the
treatment of patients with chronic anemia.



To evaluate protein depletion and other forms of
malnutrition.



To check for certain liver disorders.

2066



To evaluate the possibility of chronic gastrointestinal
bleeding. Blood loss from the digestive tract is a
common cause of iron deficiency anemia.



To help diagnose certain unusual disorders, including iron poisoning, thalassemia, hemosiderosis, and
hemochromatosis.

A serum iron test can be used without the others
to evaluate cases of iron poisoning.

Precautions
Patients should not have their blood tested for
iron within four days of a blood transfusion or tests
and treatments that use radioactive materials. Recent
high stress levels or sleep deprivation are additional
reasons for postponing iron tests.
Blood samples for iron tests should be taken early
in the morning because serum iron levels vary during
the day. This precaution is especially important in
evaluating the results of iron replacement therapy.

Description
Iron tests are performed on samples of the
patient’s blood, withdrawn from a vein into a vacuum
tube. The amount of blood taken is between 6 mL and
10 mL (1/3 of a fluid ounce). The procedure, which is
called a venipuncture, takes about five minutes.
Iron level test
The iron level test measures the amount of iron in
the blood serum that is being carried by a protein
(transferrin) in the blood plasma.
Medications and substances that can cause
increased iron levels include chloramphenicol, estrogen preparations, dietary iron supplements, alcoholic
beverages, methyldopa, and birth control pills.
Medications that can cause decreased iron levels
include ACTH, colchicine, deferoxamine, methicillin,
and testosterone.
Total iron-binding capacity (TIBC) test
The TIBC test measures the amount of iron that
the blood would carry if the transferrin were fully
saturated. Since transferrin is produced by the liver,
the TIBC can be used to monitor liver function and
nutrition.
Medications that can cause increased TIBC levels
include fluorides and birth control pills.
Medications that can cause decreased TIBC levels
include chloramphenicol and ACTH.
GALE ENCYCLOPEDIA OF MEDICINE

The transferrin test is a direct measurement of
transferrin–which is also called siderophilin–levels in
the blood. Some laboratories prefer this measurement
to the TIBC. The saturation level of the transferrin
can be calculated by dividing the serum iron level by
the TIBC.

can apply moist warm compresses if there is any
discomfort.

Normal results
Iron level test
Normal serum iron values are as follows:


Adult males: 75–175 micrograms/dL



Adult females: 65–165 micrograms/dL



Children: 50–120 micrograms/dL



Newborns: 100–250 micrograms/dL.

Ferritin test
The ferritin test measures the level of a protein in
the blood that stores iron for later use by the body.
Medications that can cause increased ferritin
levels include dietary iron supplements. In addition,
some diseases that do not directly affect the body’s
iron storage can cause artificially high ferritin levels.
These disorders include infections, late-stage cancers,
lymphomas, and severe inflammations. Alcoholics
often have high ferritin levels.

Normal TIBC values are as follows:


Adult males: 300–400 micrograms/dL



Adult females: 300–450 micrograms/dL.

Preparation

Transferrin test

Patient history

Normal transferrin values are as follows:

Before patients are tested for iron, they should be
checked for any of the following factors:


TIBC test

Prescription medications that affect iron levels,
absorption, or storage



Blood transfusion or radioactive medications within
the last four days



Recent extreme stress or sleep deprivation



Recent eating habits. Test results can be affected by
eating large amounts of iron-rich foods shortly
before the blood test.
Fasting

Patients scheduled for an iron level, TIBC, or
transferrin test should fast for 12 hours before the
blood is drawn. They are allowed to drink water.
Patients scheduled for a ferritin test do not need to
fast but they should not have any alcoholic beverages
before the test.

Aftercare
Aftercare consists of routine care of the area
around the venipuncture.

Risks
The primary risk is the possibility of a bruise or
swelling in the area of the venipuncture. The patient
GALE ENCYCLOPEDIA OF MEDICINE



Adult males: 200–400 mg/dL



Adult females: 200–400 mg/dL



Children: 203–360 mg/dL



Newborns: 130–275 mg/dL.

Normal transferrin saturation values are between
30–40%.
Ferritin test
Normal ferritin values are as follows:


Adult males: 20–300 ng/mL



Adult females: 20–120 ng/mL



Children (one month): 200–600 ng/mL



Children (two to five months): 50–200 ng/mL



Children (six months to 15 years): 7–140 ng/mL



Newborns: 25–200 ng/mL.

Abnormal results
Iron level test
Serum iron level is increased in thalassemia, hemochromatosis, severe hepatitis, liver disease, lead poisoning, acute leukemia, and kidney disease. It is also
increased by multiple blood transfusions and intramuscular iron injections.
2067

Iron tests

Transferrin test

Irritable bowel syndrome

Transferrin test

KEY TERMS
Anemia—A disorder marked by low hemoglobin
levels in red blood cells, which leads to a deficiency of oxygen in the blood.
Ferritin—A protein found in the liver, spleen, and
bone marrow that stores iron.
Hemochromatosis—A disorder of iron absorption
characterized by bronze-colored skin. It can cause
painful joints, diabetes, and liver damage if the iron
concentration is not lowered.
Hemosiderosis—An overload of iron in the body
resulting from repeated blood transfusions.
Hemosiderosis occurs most often in patients with
thalassemia.
Iron poisoning—A potentially fatal condition
caused by swallowing large amounts of iron dietary
supplements. Most cases occur in children who
have taken adult- strength iron formulas. The symptoms of iron poisoning include vomiting, bloody
diarrhea, convulsions, low blood pressure, and
turning blue.

Transferrin is increased in iron deficiency anemia,
pregnancy, hormone replacement therapy (HRT), and
the use of birth control pills.
Transferrin is decreased in protein deficiency, liver
damage, malnutrition, severe burns, kidney disease,
chronic infections, and certain genetic disorders.
Ferritin test
Ferritin is increased in liver disease, iron overload
from hemochromatosis, certain types of anemia, acute
leukemia, Hodgkin’s disease, breast cancer, thalassemia, infections, inflammatory diseases, and hemosiderosis. Ferritin levels may be normal or slightly
above normal in patients with kidney disease.
Ferritin is decreased in chronic iron deficiency and
severe protein depletion.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Plasma—The liquid part of blood.
Siderophilin—Another name for transferrin.
Thalassemia—A hereditary form of anemia that
occurs most frequently in people of Mediterranean
origin.
Transferrin—A protein in blood plasma that carries
iron derived from food intake to the liver, spleen,
and bone marrow.

Rebecca J. Frey, PhD

Irregular bite see Malocclusion

Irritable bowel syndrome
Definition

Iron levels above 350–500 micrograms/dL are
considered toxic; levels over 1000 micrograms/dL
indicate severe iron poisoning.
Serum iron level is decreased in iron deficiency
anemia, chronic blood loss, chronic diseases (lupus,
rheumatoid arthritis), late pregnancy, chronically
heavy menstrual periods, and thyroid deficiency.
TIBC test
The TIBC is increased in iron deficiency anemia,
polycythemia vera, pregnancy, blood loss, severe hepatitis, and the use of birth control pills.
The TIBC is decreased in malnutrition, severe
burns, hemochromatosis, anemia caused by infections
and chronic diseases, cirrhosis of the liver, and kidney
disease.
2068

Irritable bowel syndrome (IBS) is a common
intestinal condition characterized by abdominal pain
and cramps; changes in bowel movements (diarrhea,
constipation, or both); gassiness; bloating; nausea; and
other symptoms. There is no cure for IBS. Much about
the condition remains unknown or poorly understood;
however, dietary changes, drugs, and psychological
treatment are often able to eliminate or substantially
reduce its symptoms.

Description
IBS is the name people use today for a condition
that was once called–among other things–colitis,
mucous colitis, spastic colon, nervous colon, spastic
bowel, and functional bowel disorder. Some of these
names reflected the now outdated belief that IBS is a
purely psychological disorder, a product of the
patient’s imagination. Although modern medicine
GALE ENCYCLOPEDIA OF MEDICINE

No one knows for sure how many Americans
suffer from IBS. Surveys indicate a range of 10–20%,
with perhaps as many as 30% of Americans experiencing IBS at some point in their lives. IBS normally
makes its first appearance during young adulthood,
and in half of all cases symptoms begin before age 35.
Women with IBS outnumber men by two to one, for
reasons that are not yet understood. IBS is responsible
for more time lost from work and school than any
medical problem other than the common cold. It
accounts for a substantial proportion of the patients
seen by specialists in diseases of the digestive system
(gastroenterologists). Yet only half–possibly as few as
15%–of IBS sufferers ever consult a doctor.

Causes and symptoms
Symptoms
The symptoms of IBS tend to rise and fall in intensity rather than growing steadily worse over time. They
always include abdominal pain, which may be relieved
by defecation; diarrhea or constipation; or diarrhea
alternating with constipation. Other symptoms–which
vary from person to person–include cramps; gassiness;
bloating; nausea; a powerful and uncontrollable urge to
defecate (urgency); passage of a sticky fluid (mucus)
during bowel movements; or the feeling after finishing
a bowel movement that the bowels are still not completely empty. The accepted diagnostic criteria–known as
the Rome criteria–require at least three months of continuous or recurrent symptoms before IBS can be confirmed. According to Christine B. Dalton and Douglas
A. Drossman in the American Family Physician, an
estimated 70% of IBS cases can be described as
‘‘mild;’’ 25% as ‘‘moderate;’’ and 5% as ‘‘severe.’’ In
mild cases the symptoms are slight. As a general rule,
they are not present all the time and do not interfere
with work and other normal activities. Moderate
IBS occasionally disrupts normal activities and may
cause some psychological problems. People with severe
IBS often find living a normal life impossible and
experience crippling psychological problems as a result.
For some the physical pain is constant and intense.
Causes
Researchers remain unsure about the cause or
causes of IBS. It is called a functional disorder
because it is thought to result from changes in the
GALE ENCYCLOPEDIA OF MEDICINE

activity of the major part of the large intestine (the
colon). After food is digested by the stomach and
small intestine, the undigested material passes in
liquid form into the colon, which absorbs water and
salts. This process may take several days. In a healthy
person the colon is quiet during most of that period
except after meals, when its muscles contract in a
series of wavelike movements called peristalsis.
Peristalsis helps absorption by bringing the undigested material into contact with the colon wall. It
also pushes undigested material that has been converted into solid or semisolid feces toward the
rectum, where it remains until defecation. In IBS,
however, the normal rhythm and intensity of peristalsis is disrupted. Sometimes there is too little
peristalsis, which can slow the passage of undigested
material through the colon and cause constipation.
Sometimes there is too much, which has the opposite
effect and causes diarrhea. A Johns Hopkins
University study found that healthy volunteers
experienced 6–8 contractions of the colon each day,
compared with up to 25 contractions a day for volunteers suffering from IBS with diarrhea, and an almost
complete absence of contractions among constipated
IBS volunteers. In addition to differences in the
number of contractions, many of the IBS volunteers
experienced powerful spasmodic contractions affecting a larger-than-normal area of the colon–‘‘like
having a Charlie horse in the gut,’’ according to one
of the investigators.
DIET. Some kinds of food and drink appear to
play a key role in triggering IBS attacks. Food and
drink that healthy people can ingest without any
trouble may disrupt peristalsis in IBS patients, which
probably explains why IBS attacks often occur shortly
after meals. Chocolate, milk products, caffeine
(in coffee, tea, colas, and other drinks), and large
quantities of alcohol are some of the chief culprits.
Other kinds of food have also been identified as
problems, however, and the pattern of what can and
cannot be tolerated is different for each person.
Characteristically, IBS symptoms rarely occur at
night and disrupt the patient’s sleep.
STRESS. Stress is an important factor in IBS
because of the close nervous system connections
between the brain and the intestines. Although
researchers do not yet understand all of the links
between changes in the nervous system and IBS, they
point out the similarities between mild digestive upsets
and IBS. Just as healthy people can feel nauseated or
have an upset stomach when under stress, people with
IBS react the same way, but to a greater degree.
Finally, IBS symptoms sometimes intensify during

2069

Irritable bowel syndrome

recognizes that stress can trigger IBS attacks, medical
specialists agree that IBS is a genuine physical
disorder–or group of disorders–with specific identifiable characteristics.

Irritable bowel syndrome

menstruation, which suggests that female reproductive hormones are another trigger.

Diagnosis
Diagnosing IBS is a fairly complex task because
the disorder does not produce changes that can be
identified during a physical examination or by laboratory tests. When IBS is suspected, the doctor (who can
be either a family doctor or a specialist) needs to
determine whether the patient’s symptoms satisfy the
Rome criteria. The doctor must rule out other conditions that resemble IBS, such as Crohn’s disease and
ulcerative colitis. These disorders are ruled out by
questioning the patient about his or her physical and
mental health (the medical history), performing a
physical examination, and ordering laboratory tests.
Normally the patient is asked to provide a stool sample that can be tested for blood and intestinal parasites. In some cases x rays or an internal examination
of the colon using a flexible instrument inserted
through the anus (a sigmoidoscope or colonoscope)
is necessary. The doctor also may ask the patient to try
a lactose-free diet for two or three weeks to see
whether lactose intolerance is causing the symptoms.

Treatment
Dietary changes, sometimes supplemented by
drugs or psychotherapy, are considered the key to
successful treatment. The following approach, offered
by Dalton and Drossman, is typical of the advice
found in the medical literature on IBS. The authors
tie their approach to the severity of the patient’s
symptoms:
Mild symptoms
Dalton and Drossman recommend a low-fat,
high-fiber diet. Problem-causing substances such as
lactose, caffeine, beans, cabbage, cucumbers, broccoli,
fatty foods, alcohol, and medications should be
identified and avoided. Bran or 15-25 grams a day
of an over-the-counter psyllium laxative (Metamucil
or Fiberall) may also help both constipation and diarrhea. The patient can still have milk or milk products if
lactose intolerance is not a problem. People with irregular bowel habits–particularly constipated patients–
may be helped by establishing set times for meals and
bathroom visits.
Moderate symptoms
The advice given by Dalton and Drossman in mild
cases applies here as well. They also suggest that
2070

Normal and diseased (center) colons. Areas of constriction in
the colon cause constipation, while areas of distention cause
diarrhea. (John Bavosi/Science Photo Library. Custom Medical
Stock Photo. Reproduced by permission.)

patients keep a diary of symptoms for two or three
weeks, covering daily activities including meals, and
emotional responses to events. The doctor can then
review the diary with the patient to identify possible
problem areas.
Although a high-fiber diet remains the standard
treatment for constipated patients, such laxatives as
lactulose (Chronulac) or sorbitol may be prescribed.
Loperamide (Imodium) and cholestyramine (Questran)
are suggested for diarrhea. Abdominal pain after
meals can be reduced by taking antispasmodic drugs
such as hyoscyamine (Anaspaz, Cystospaz, or Levsin)
or dicyclomine (Bemote, Bentyl, or Di-Spaz) before
eating.
Dalton and Drossman also suggest psychological
counseling or behavioral therapy for some patients to
reduce anxiety and to learn to cope with the pain and
other symptoms of IBS. Relaxation therapy, hypnosis,
biofeedback, and cognitive-behavioral therapy are
examples of behavioral therapy.
Severe symptoms
When IBS produces constant pain that interferes
with everyday life, antidepressant drugs can help by
blocking pain transmission from the nervous system.
Dalton and Drossman also underscore the importance
GALE ENCYCLOPEDIA OF MEDICINE

Anus—The opening at the lower end of the rectum.
Crohn’s disease—A disease characterized by
inflammation of the intestines. Its early symptoms
may resemble those of IBS.
Defecation—Passage of feces through the anus.
Feces—Undigested food and other waste that is
eliminated through the anus. Feces are also called
fecal matter or stools.
Lactose—A sugar found in milk and milk products.
Some people are lactose intolerant, meaning
they have trouble digesting lactose. Lactose intolerance can produce symptoms resembling those
of IBS.
Peristalsis—The periodic waves of muscular contractions that move food through the intestines
during the process of digestion.
Ulcerative colitis—A disease that inflames and
causes breaks (ulcers) in the colon and rectum,
which are parts of the large intestine.

of an ongoing
relationship.

and

supportive

doctor-patient

Prognosis
IBS is not a life-threatening condition. It does
not cause intestinal bleeding or inflammation, nor
does it cause other bowel diseases or cancer.
Although IBS can last a lifetime, in up to 30% of
cases the symptoms eventually disappear. Even if the
symptoms cannot be eliminated, with appropriate
treatment they can usually be brought under control
to the point where IBS becomes merely an occasional
inconvenience. Treatment requires a long-term
commitment, however; six months or more may be
needed before the patient notices substantial
improvement.
Resources
ORGANIZATIONS

International Foundation for Functional Gastrointestinal
Disorders. P.O. Box 17864, Milwaukee, WI 53217.
(888) 964-2001. <http://www.iffgd.org>.
National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.

Howard Baker

Alternative treatment
Alternative and mainstream approaches to IBS
treatment overlap to a certain extent. Like mainstream
doctors, alternative practitioners advise a high-fiber
diet to reduce digestive system irritation. They also
suggest avoiding alcohol, caffeine, and fatty, gassy,
or spicy foods. Recommended stress management
techniques include yoga, meditation, hypnosis, biofeedback, and reflexology. Reflexology is a technique
of foot massage that is thought to relieve diarrhea,
constipation, and other IBS symptoms.
Alternative medicine also emphasizes such herbal
remedies as ginger (Zingiber officinale), buckthorn
(Rhamnus purshiana), and enteric-coated peppermint
oil. Enteric coating prevents digestion until the peppermint oil reaches the small intestine, thus avoiding
irritation of the upper part of the digestive tract.
Chamomile (Matricaria recutita), valerian (Valeriana
officinalis), rosemary (Rosemarinus officinalis), lemon
balm (Melissa officinalis), and other herbs are recommended for their antispasmodic properties. The list of
alternative treatments for IBS is in fact quite long. It
includes aromatherapy, homeopathy, hydrotherapy,
GALE ENCYCLOPEDIA OF MEDICINE

Ischemia
Definition
Ischemia is an insufficient supply of blood to an
organ, usually due to a blocked artery.

Description
Myocardial ischemia is an intermediate condition
in coronary artery disease during which the heart tissue
is slowly or suddenly starved of oxygen and other
nutrients. Eventually, the affected heart tissue will
die. When blood flow is completely blocked to the
heart, ischemia can lead to a heart attack. Ischemia
can be silent or symptomatic. According to the
American Heart Association, up to four million
Americans may have silent ischemia and be at high
risk of having a heart attack with no warning.
2071

Ischemia

juice therapy, acupuncture, chiropractic, osteopathy,
naturopathic medicine, and Chinese traditional herbal
medicine.

KEY TERMS

Ischemia

Symptomatic ischemia is characterized by chest
pain called angina pectoris. The American Heart
Association estimates that nearly seven million
Americans have angina pectoris, usually called
angina. Angina occurs more frequently in women
than in men, and in blacks and Hispanics more than
in whites. It also occurs more frequently as people
age–25% of women over the age of 85 and 27% of
men who are 80–84 years old have angina.



Heredity. People whose parents have coronary artery
disease are more likely to develop it. African
Americans are also at higher risk.



Sex. Men are more likely to have heart attacks than
women, and to have them at a younger age.



Age. Men who are 45 years of age and older and
women who are 55 years of age and older are considered to be at risk.

People with angina are at risk of having a heart
attack. Stable angina occurs during exertion, can be
quickly relieved by resting or taking nitroglycerine,
and lasts from three to twenty minutes. Unstable
angina, which increases the risk of a heart attack,
occurs more frequently, lasts longer, is more severe,
and may cause discomfort during rest or light
exertion.



Smoking. Smoking increases both the chance of
developing coronary artery disease and the chance
of dying from it. Second hand smoke may also
increase risk.



High cholesterol. Risk of developing coronary artery
disease increases as blood cholesterol levels increase.
When combined with other factors, the risk is even
greater.



High blood pressure. High blood pressure makes the
heart work harder, and with time, weakens it. When
combined with obesity, smoking, high cholesterol, or
diabetes, the risk of heart attack or stroke increases
several times.



Lack of physical activity. Lack of exercise increases
the risk of coronary artery disease.



Diabetes mellitus. The risk of developing coronary
artery disease is seriously increased for diabetics.



Obesity. Excess weight increases the strain on the
heart and increases the risk of developing coronary
artery disease, even if no other risk factors are present. Obesity increases blood pressure and blood
cholesterol, and can lead to diabetes.



Stress and anger. Some scientists believe that
stress and anger can contribute to the development of coronary artery disease. Stress increases
the heart rate and blood pressure and can injure
the lining of the arteries. Angina attacks often
occur after anger, as do many heart attacks and
strokes.

Ischemia can also occur in the arteries of the
brain, where blockages can lead to a stroke. About
80–85% of all strokes are ischemic. Most blockages in
the cerebral arteries are due to a blood clot, often in
an artery narrowed by plaque. Sometimes, a blood
clot in the heart or aorta travels to a cerebral artery.
A transient ischemic attack (TIA) is a ‘‘mini-stroke’’
caused by a temporary deficiency of blood supply to
the brain. It occurs suddenly, lasts a few minutes to
a few hours, and is a strong warning sign of an
impending stroke. Ischemia can also effect intestines,
legs, feet and kidneys. Pain, malfunctions, and damage
in those areas may result.

Causes and symptoms
Ischemia is almost always caused by blockage of
an artery, usually due to atherosclerotic plaque.
Myocardial ischemia is also caused by blood clots
(which tend to form on plaque), artery spasms or
contractions, or any of these factors combined. Silent
ischemia is usually caused by emotional or mental
stress or by exertion, but there are no symptoms.
Angina is usually caused by increased oxygen demand
when the heart is working harder than usual, for
example, during exercise, or during mental or physical
stress. According to researchers at Harvard
University, physical stress is harder on the heart than
mental stress. A TIA is caused by a blood clot briefly
blocking a cerebral artery.
Risk factors
The risk factors for myocardial ischemia are the
same as those for coronary artery disease. For TIA,
coronary artery disease is also a risk factor.
2072

Angina symptoms include:


A tight, squeezing, heavy, burning, or choking pain
that is usually beneath the breastbone—the pain may
spread to the throat, jaw, or one arm



A feeling of heaviness or tightness that is not painful



A feeling similar to gas or indigestion



Attacks brought on by exertion and relieved by
rest.

If the pain or discomfort continues or intensifies,
immediate medical help should be sought, ideally
within 30 minutes.
GALE ENCYCLOPEDIA OF MEDICINE



Sudden weakness, tingling, or numbness, usually in
one arm or leg or both the arm and leg on the same
side of the body, as well as sometimes in the face



Sudden loss of coordination



Loss of vision or double vision



Difficulty speaking



Vertigo and loss of balance.

Diagnosis
Diagnostic tests for myocardial ischemia include:
resting, exercise, or ambulatory electrocardiograms;
scintigraphic studies (radioactive heart scans); echocardiography; coronary angiography; and, rarely, positron emission tomography. Diagnostic tests for TIA
include physician review of symptoms, computed
tomography scans (CT scans), carotid artery ultrasound (Doppler ultrasonography), and magnetic resonance imaging. Angiography is the best test for
ischemia of any organ.
An electrocardiogram (ECG) shows the heart’s
activity and may reveal a lack of oxygen. Electrodes
covered with conducting jelly are placed on the
patient’s chest, arms, and legs. Impulses of the heart’s
activity are recorded on paper. The test takes about
10 minutes and is performed in a physician’s office.
About 25% of patients with angina have normal electrocardiograms. Another type of electrocardiogram,
the exercise stress test, measures response to exertion
when the patient is exercising on a treadmill or a
stationary bike. It is performed in a physician’s office
or an exercise laboratory and takes 15 to 30 minutes.
This test is more accurate than a resting ECG in
diagnosing ischemia. Sometimes an ambulatory ECG
is ordered. For this test, the patient wears a portable
ECG machine called a Holter monitor for 12, 24, or 48
hours.
Myocardial perfusion scintigraphy and radionuclide angiography are nuclear studies involving the
injection of a radioactive material (e.g., thallium)
which is absorbed by healthy tissue. A gamma scintillation camera displays and records a series of images
of the radioactive material’s movement through the
heart. Both tests are usually performed in a hospital’s
nuclear medicine department and take about 30 minutes to an hour. A perfusion scan is sometimes performed at the end of a stress test.
An echocardiogram uses sound waves to create an
image of the heart’s chambers and valves. The technician applies gel to a handheld transducer then presses
GALE ENCYCLOPEDIA OF MEDICINE

it against the patient’s chest. The heart’s sound waves
are converted into an image on a monitor. Performed
in a cardiology outpatient diagnostic laboratory, the
test takes 30 minutes to an hour. It can reveal abnormalities in the heart wall that indicate ischemia, but it
doesn’t evaluate the coronary arteries directly.
Coronary angiography is the most accurate diagnostic technique, but it is also the most invasive. It
shows the heart’s chambers, great vessels, and coronary arteries by using a contrast solution and x-ray
technology. A moving picture is recorded of the
blood flow through the coronary arteries. The patient
is awake, but sedated, and connected to ECG electrodes and an intravenous line. A local anesthetic is
injected. The cardiologist then inserts a catheter into
a blood vessel and guides it into the heart. Coronary
angiography is performed in a cardiac catheterization
laboratory and takes from half an hour to two hours.
Positron emission tomography (PET) is a noninvasive nuclear test used to evaluate the heart tissue.
A PET scanner traces high-energy gamma rays
released from radioactive particles to provide threedimensional images of the heart tissue. Performed at a
hospital, it usually takes from one hour to one hour
and 45 minutes. PET is very expensive and not widely
available.
Computed tomography scans (CT scans) and
magnetic resonance imaging (MRI) are computerized
scanning methods. CT scanning uses a thin x-ray beam
to show three-dimensional views of soft tissues. It is
performed at a hospital or clinic and takes less than a
minute. MRI uses a magnetic field to produce clear,
cross-sectional images of soft tissues. The patient lies
on a table which slides into a tunnel-like scanner. It is
usually performed at a hospital and takes about 30
minutes.

Treatment
Angina is treated with drug therapy and surgery.
Drugs such as nitrates, beta-blockers, and calcium
channel blockers relieve chest pain, but they cannot
clear blocked arteries. Aspirin helps prevent blood
clots. Surgical procedures include percutaneous transluminal coronary angioplasty and coronary artery
bypass graft surgery.
Nitroglycerin is the classic treatment for angina. It
quickly relieves pain and discomfort by opening the
coronary arteries and allowing more blood to flow to
the heart. Beta blockers reduce the amount of oxygen
required by the heart during stress. Calcium channel
blockers help keep the arteries open and reduce blood
2073

Ischemia

TIA symptoms include:

Ischemia

open. This stenting procedure is becoming more common. Another experimental procedure uses a laser to
drill channels in the heart muscle to increase blood
supply.
TIAs are treated by drugs that control high blood
pressure and reduce the likelihood of blood clots and
surgery. Aspirin is commonly used and anticoagulants
are sometimes used to prevent blood clots. In some
cases, carotid endarterectomy surgery is performed to
help prevent further TIAs. The procedure involves
removing arterial plaque from inside blood vessels.

This patient’s foot is affected with ischemia. Ischemia occurs
when there is an insufficient supply of blood to a specific
organ or tissue. (Photograph by Dr. P. Marazzi, Photo
Researchers, Inc. Reproduced by permission.)

The use of chelation therapy, a long-term injection
by a physician of a cocktail of synthetic amino acid,
ethylenediaminetetracetric acid, and anticoagulant
drugs and nutrients, is controversial.

Alternative treatment
pressure. Aspirin helps prevent blood clots from forming on plaques.
Percutaneous transluminal coronary angioplasty
and coronary artery bypass graft surgery are invasive
procedures which improve blood flow in the coronary
arteries. Percutaneous transluminal coronary angioplasty is a non-surgical procedure in which a catheter
tipped with a balloon is threaded from a blood vessel
in the thigh into the blocked artery. The balloon is
inflated, compressing the plaque to enlarge the blood
vessel and open the blocked artery. The balloon is
deflated and the catheter is removed. The procedure
is performed by a cardiologist in a hospital and generally requires a two-day stay. Sometimes a metal stent
is placed in the artery to prevent closing of the artery.
In coronary artery bypass graft, called bypass
surgery, a detour is built around the coronary artery
blockage with a healthy leg vein or chest wall artery.
The healthy vein or artery then supplies oxygen-rich
blood to the heart. Bypass surgery is major surgery
appropriate for patients with blockages in two or three
major coronary arteries or severely narrowed left main
coronary arteries, as well as those who have not
responded to other treatments. It is performed in a
hospital under general anesthesia using a heart-lung
machine to support the patient while the healthy vein
or artery is attached to the coronary artery.
There are several experimental surgical procedures: atherectomy, where the surgeon shaves off and
removes strips of plaque from the blocked artery; laser
angioplasty, where a catheter with a laser tip is
inserted to burn or break down the plaque; and insertion of a metal coil, called a stent, that can be
implanted permanently to keep a blocked artery
2074

Ischemia can be life-threatening. Although there
are alternative treatments for angina, traditional medical care may be necessary. Prevention of the cause of
ischemia, primarily atherosclerosis, is primary. This
becomes even more important for people with a family
history of heart disease. Dietary modifications, especially the reduction or elimination of saturated fats
(primarily found in meat), are essential. Increased
fiber (found in fresh fruits and vegetables, grains,
and beans) can help the body eliminate excessive cholesterol through the stools. Exercise, particularly aerobic exercise, is essential for circulation health. Not
smoking will prevent damage from smoke and the
harmful substances it contains.
Abana, a mixture of herbs and minerals used in
Ayurvedic medicine, can reduce the frequency and
severity of angina attacks. Western herbal medicine
recommends hawthorn (Crataegus laevigata or
C. oxyacantha) to relieve long-term angina, since it
strengthens the contractility of the heart muscles.
Nutritional supplements and botanical medicines that
act as antioxidants, for example, vitamins C and E,
selenium, gingko (Gingko biloba), bilberry (Vaccinium
myrtillus), and hawthorn, can help prevent initial
arterial injury that can lead to the formation of plaque
deposits. Cactus (Cactus grandiflorus) is a homeopathic remedy used for pain relief during an attack.
Mind/body relaxation techniques such as yoga and
biofeedback can help control strong emotions and
stress.

Prognosis
ted,

In many cases, ischemia can be successfully treabut the underlying disease process of
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
A healthy lifestyle, including eating right, getting
regular exercise, maintaining a healthy weight, not
smoking, drinking in moderation, not using illegal
drugs, controlling hypertension, and managing stress
are practices that can reduce the risk of ischemia progressing to a heart attack or stroke.
A healthy diet includes a variety of foods that are
low in fat, especially saturated fat; low in cholesterol;
and high in fiber. Plenty of fruits and vegetables
should be eaten and sodium should be limited. Fat
should comprise no more than 30% of total daily
calories. Cholesterol should be limited to about 300
mg and sodium to about 2,400 mg per day.
Moderate aerobic exercise lasting about 30 minutes four or more times per week is recommended for
maximum heart health, according to the Centers for
Disease Control and Prevention and the American
College of Sports Medicine. Three 10-minute exercise
periods are also beneficial. If any risk factors are present, a physician’s clearance should be obtained before
starting exercise.
Maintaining a desirable body weight is also
important. People who are 20% or more over their
ideal body weight have an increased risk of developing
coronary artery disease or stroke.
Smoking has many adverse effects on the heart
and arteries, so should be avoided. Heart damage
caused by smoking can be improved by quitting.
Several studies have shown that ex-smokers face the
same risk of heart disease as non-smokers within five
to ten years of quitting.
Excessive drinking can increase risk factors for
heart disease. Modest consumption of alcohol, however, can actually protect against coronary artery disease. The American Heart Association defines
moderate consumption as one ounce of alcohol per
day–roughly one cocktail, one 8-ounce glass of wine,
or two 12-ounce glasses of beer.
Commonly used illegal drugs can seriously harm
the heart and should never be used. Even stimulants
like ephedra and decongestants like pseudoephedrine
can be harmful to patients with hypertension or heart
disease.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Atherosclerosis—A process in which the walls of
the arteries thicken due to the accumulation of plaque in the blood vessels. Atherosclerosis is the
cause of most coronary artery disease.
Coronary artery disease—A narrowing or blockage, due to atherosclerosis, of the arteries that provide oxygen and nutrients to the heart. When blood
flow is cut-off, the result is a heart attack.
Plaque—A deposit of fatty and other substances that
accumulate in the lining of the artery wall.
Stroke—A sudden decrease or loss of consciousness caused by rupture or blockage of a blood vessel
by a blood clot or hemorrhage in the brain.
Ischemic strokes are caused by blood clots in a
cerebral artery.

Treatment should be sought for hypertension.
High blood pressure can be completely controlled
through lifestyle changes and medication. Stress,
which can increase the risk of a heart attack or stroke,
should also be managed. While it cannot always be
avoided, it can be controlled.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave.
Dallas, TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. P.O. Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto

Isocarboxazid see Monoamine oxidase
inhibitors

Isolation
Definition
Isolation refers to the precautions that are taken
in the hospital to prevent the spread of an infectious
2075

Isolation

atherosclerosis is usually not ‘‘cured.’’ New diagnostic
techniques enable doctors to identify ischemia earlier.
New technologies and surgical procedures can prevent
angina from leading to a heart attack or TIA from
resulting in a stroke. The outcome for patients with
silent ischemia has not been well established.

Isolation

agent from an infected or colonized patient to susceptible persons.

Purpose
Isolation practices are designed to minimize the
transmission of infection in the hospital, using current
understanding of the way infections can transmit.
Isolation should be done in a user friendly, wellaccepted, inexpensive way that interferes as little as
possible with patient care, minimizes patient discomfort, and avoids unnecessary use.

Precautions
The type of precautions used should be viewed as
a flexible scale that may range from the least to the
most demanding methods of prevention. These methods should always take into account that differences
exist in the way that diseases are spread. Recognition
and understanding of these differences will avoid use
of insufficient or unnecessary interventions.

Description
Isolation practices can include placement in a private room or with a select roommate, the use of protective barriers such as masks, gowns and gloves, a
special emphasis on handwashing (which is always
very important), and special handling of contaminated
articles. Because of the differences among infectious
diseases, more than one of these precautions may be
necessary to prevent spread of some diseases but may
not be necessary for others.
The Centers for Disease Control and Prevention
(CDC) and the Hospital Infection Control Practice
Advisory Committee (HICPAC) have led the way in
defining the guidelines for hospital-based infection
precautions. The most current system recommended
for use in hospitals consists of two levels of precautions. The first level is Standard Precautions which
apply to all patients at all times because signs and
symptoms of infection are not always obvious and
therefore may unknowingly pose a risk for a susceptible person. The second level is known as
Transmission-Based Precautions which are intended
for individuals who have a known or suspected infection with certain organisms.
Frequently, patients are admitted to the hospital
without a definite diagnosis, but with clues to suggest
an infection. These patients should be isolated with the
appropriate precautions until a definite diagnosis is
made.
2076

Standard Precautions
Standard Precautions define all the steps that
should be taken to prevent spread of infection from
person to person when there is an anticipated contact
with:


Blood



Body fluids



Secretions, such as phlegm



Excretions, such as urine and feces (not including
sweat) whether or not they contain visible blood



Nonintact skin, such as an open wound



Mucous membranes, such as the mouth cavity.

Standard Precautions includes the use of one or
combinations of the following practices. The level of
use will always depend on the anticipated contact with
the patient:


Handwashing, the most important infection control
method



Use of latex or other protective gloves



Masks, eye protection and/or face shield



Gowns



Proper handling of soiled patient care equipment



Proper environmental cleaning



Minimal handling of soiled linen



Proper disposal of needles and other sharp equipment such as scalpels



Placement in a private room for patients who cannot
maintain appropriate cleanliness or contain body
fluids.
Transmission Based Precautions

Transmission Based Precautions may be needed
in addition to Standard Precautions for selected
patients who are known or suspected to harbor certain
infections. These precautions are divided into three
categories that reflect the differences in the way infections are transmitted. Some diseases may require more
than one isolation category.
AIRBORNE PRECAUTIONS. Airborne Precautions
prevent diseases that are transmitted by minute particles
called droplet nuclei or contaminated dust particles.
These particles, because of their size, can remain suspended in the air for long periods of time; even after the
infected person has left the room. Some examples of
diseases requiring these precautions are tuberculosis,
measles, and chickenpox.

GALE ENCYCLOPEDIA OF MEDICINE

Colonized—This occurs when a microorganism is
found on or in a person without causing a disease.
Disinfected—Decreased the number of microorganisms on or in an object.
Latex—A rubber material which gloves and condoms are made from.
Phlegm—Another word for sputum; material
coughed up from a person’s airways.
Stethoscope—A medical instrument for listening to
a patient’s heart and lungs.

A patient needing Airborne Precautions should be
assigned to a private room with special ventilation
requirements. The door to this room must be closed
at all possible times. If a patient must move from the
isolation room to another area of the hospital, the
patient should be wearing a mask during the transport. Anyone entering the isolation room to provide
care to the patient must wear a special mask called a
respirator.
DROPLET PRECAUTIONS. Droplet Precautions pre-

vent the spread of organisms that travel on particles
much larger than the droplet nuclei. These particles do
not spend much time suspended in the air, and usually
do not travel beyond a several foot range from the
patient. These particles are produced when a patient
coughs, talks, or sneezes. Examples of disease requiring droplet precautions are meningococcal meningitis
(a serious bacterial infection of the lining of the brain),
influenza, mumps, and German measles (rubella).
Patients who require Droplet Precautions should
be placed in a private room or with a roommate who is
infected with the same organism. The door to the
room may remain open. Health care workers will
need to wear masks within 3 ft of the patient.
Patients moving about the hospital away from the
isolation room should wear a mask.
CONTACT PRECAUTIONS. Contact Precautions
prevent spread of organisms from an infected patient
through direct (touching the patient) or indirect
(touching surfaces or objects that that been in contact
with the patient) contact. Examples of patients who
might be placed in Contact Precautions are those
infected with:


Antibiotic-resistant bacteria



Hepatitis A

GALE ENCYCLOPEDIA OF MEDICINE



Scabies



Impetigo



Lice.

Itching

KEY TERMS

This type of precaution requires the patient to be
placed in a private room or with a roommate who has
the same infection. Health care workers should wear
gloves when entering the room. They should change
their gloves if they touch material that contains large
volumes of organisms such as soiled dressings. Prior to
leaving the room, health care workers should remove
the gloves and wash their hands with medicated soap.
In addition, they may need to wear protective gowns if
there is a chance of contact with potentially infective
materials such as diarrhea or wound drainage that
cannot be contained or if there is likely to be extensive
contact with the patient or environment.
Patient care items, such as a stethoscope, that are
used for a patient in Contact Precautions should not
be shared with other patients unless they are properly
cleaned and disinfected before reuse. Patients should
leave the isolation room infrequently.
Resources
BOOKS

Edmond, M. ‘‘Isolation.’’ In A Practical Handbook for
Hospital Epidemiologists, edited by L. A. Herwaldt and
M. D. Decker. Thorofare, NJ: Slack Inc., 1998.

Suzanne M. Lutwick, MPH

Isoniazid see Antituberculosis drugs
Isosorbide dinitrate see Antiangina drugs
Isotretinoin see Antiacne drugs
Isradipine see Calcium channel blockers

Itching
Definition
Itching is an intense, distracting irritation or tickling sensation that may be felt all over the skin’s surface, or confined to just one area. The medical term for
itching is pruritus.

Description
Itching instinctively leads most people to scratch
the affected area. Different people can tolerate different amounts of itching, and anyone’s threshold of
2077

Itching

tolerance can be changed due to stress, emotions, and
other factors. In general, itching is more severe if the
skin is warm, and if there are few distractions. This is
why people tend to notice itching more at night.

Many skin conditions cause an itchy rash. These
include:


Atopic dermatitis



Chickenpox



Contact dermatitis

The biology underlying itching is not fully understood. It is believed that itching results from the interactions of several different chemical messengers.
Although itching and pain sensations were at one time
thought to be sent along the same nerve pathways,
researchers reported the discovery in 2003 of itch-specific nerve pathways. Nerve endings that are specifically
sensitive to itching have been named pruriceptors.



Dermatitis herpetiformis (occasionally)



Eczema



Fungus infections (such as athlete’s foot)



Hives (urticaria)



Insect bites



Lice

Research into itching has been helped by the
recent invention of a mechanical device called the
Matcher, which electrically stimulates the patient’s
left hand. When the intensity of the stimulation equals
the intensity of itching that the patient is experiencing
elsewhere in the body, the patient stops the stimulation
and the device automatically records the measurement. The Matcher was found to be sensitive to
immediate changes in the patient’s perception of itching as well as reliable in its measurements.



Lichen planus



Neurodermatitis (lichen simplex chronicus)



Psoriasis (occasionally)



Scabies.

Causes and symptoms

Stress and emotional upset can make itching worse,
no matter what the underlying cause. If emotional problems are the primary reason for the itch, the condition
is known as psychogenic itching. Some people become
convinced that their itch is caused by a parasite; this
conviction is often linked to burning sensations in the
tongue, and may be caused by a major psychiatric
disorder.
Generalized itching
Itching that occurs all over the body may indicate
a medical condition such as diabetes mellitus, liver
disease, kidney failure, jaundice, thyroid disorders
(and rarely, cancer). Blood disorders such as leukemia,
and lymphatic conditions such as Hodgkin’s disease
may sometimes cause itching as well.
Some people may develop an itch without a rash
when they take certain drugs (such as aspirin, codeine,
cocaine); others may develop an itchy red ‘‘drug rash’’
or hives because of an allergy to a specific drug. Some
medications given to cancer patients may also cause
itching.
Itching also may be caused when any of the family
of hookworm larvae penetrate the skin. This includes
swimmer’s itch and creeping eruption caused by cat or
dog hookworm, and ground itch caused by the ‘‘true’’
hookworm.
2078

On the other hand, itching all over the body can be
caused by something as simple as bathing too often,
which removes the skin’s natural oils and may make
the skin too dry and scaly.
Localized itching
Specific itchy areas may occur if a person comes in
contact with soap, detergents, and wool or other
rough-textured, scratchy material. Adults who have
hemorrhoids, anal fissure, or persistent diarrhea may
notice itching around the anus (called ‘‘pruritus ani’’).
In children, itching in this area is most likely due to
worms.
Intense itching in the external genitalia in women
(‘‘pruritus vulvae’’) may be due to candidiasis, hormonal changes, or the use of certain spermicides or vaginal suppositories, ointments, or deodorants.
It is also common for older people to suffer from
dry, itchy skin (especially on the back) for no obvious
reason. Younger people also may notice dry, itchy skin
in cold weather. Itching is also a common complaint
during pregnancy.

Diagnosis
Itching is a symptom that is quite obvious to its
victim. Someone who itches all over should seek medical care. Because itching can be caused by such a wide
variety of triggers, a complete physical exam and medical history will help diagnose the underlying problem.
A variety of blood and stool tests may help determine
the underlying cause.
GALE ENCYCLOPEDIA OF MEDICINE

Antihistamines such as diphenhydramine (Benadryl)
can help relieve itching caused by hives, but will not affect
itching from other causes. Most antihistamines also make
people sleepy, which can help patients sleep who would
otherwise be awake from the itch.
Specific treatment of itching depends on the underlying condition that causes it. In general, itchy skin
should be treated very gently. While scratching may
temporarily ease the itch, in the long run scratching
just makes it worse. In addition, scratching can lead
to an endless cycle of itch–scratch–more itching.
To avoid the urge to scratch, a person can apply a
cooling or soothing lotion or cold compress when the
urge to scratch occurs. Soaps are often irritating to the
skin, and can make an itch worse; they should be
avoided, or used only when necessary.
Creams or ointments containing cortisone may
help control the itch from insect bites, contact dermatitis or eczema. Cortisone cream should not be applied
to the face unless a doctor prescribes it.
Probably the most common cause of itching is dry
skin. There are a number of simple things a person can
do to ease the annoying itch:


Do not wear tight clothes



Avoid synthetic fabrics



Do not take long baths



Wash the area in lukewarm water with a little baking
soda



For generalized itching, take a lukewarm shower



Try a lukewarm oatmeal (or Aveeno) bath for generalized itching



Apply bath oil or lotion (without added colors or
scents) right after bathing.

Itching may also be treated with whole-body medications. In addition to antihistamines, some of these
systemic treatments include:

People who itch as a result of mental problems or
stress should seek help from a mental health expert.
Alternative and complementary therapies
A well-balanced diet that includes carbohydrates,
fats, minerals, proteins, vitamins, and liquids will help
to maintain skin health. Capsules that contain eicosapentaenoic acid, which is obtained from herring,
mackerel, or salmon, may help to reduce itching.
Vitamin A plays an important role in skin health.
Vitamin E (capsules or ointment) may reduce itching.
Patients should check with their treating physician
before using supplements.
Homeopathy has been reported to be effective in
treating systemic itching associated with hemodialysis.
Baths containing oil with milk or oatmeal are effective at relieving localized itching. Evening primrose oil
may soothe itching and may be as effective as corticosteroids. Calendula cream may relieve short-term itching. Other herbal treatments that have been recently
reported to relieve itching include sangre de drago, a
preparation made with sap from a South American
tree; and a mixture of honey, olive oil, and beeswax.
Distraction, music therapy, relaxation techniques,
and visualization may be useful in relieving itching.
Ultraviolet light therapy may relieve itching associated with conditions of the skin, kidneys, blood,
and gallbladder. There are some reports of the use of
acupuncture and transcutaneous electrical nerve stimulators (TENS) to relieve itching.

Prognosis
Most cases of itching go away when the underlying cause is treated successfully.

Prevention
There are certain things people can do to avoid
itchy skin. Patients who tend toward itchy skin should:


Avoid a daily bath



tricyclic antidepressants



Use only lukewarm water when bathing



sedatives or tranquilizers



Use only gentle soap



such selective serotonin reputake inhibitors as paroxetine (Paxil) and sertraline (Zoloft)



Pat dry, not rub dry, after bathing, leaving a bit of
water on the skin



binding agents (such as cholestyramine which
relieves itching associated with kidney or liver
disease).



Apply a moisture-holding ointment or cream after
the bath



Use a humidifier in the home.



aspirin



cimetidine

GALE ENCYCLOPEDIA OF MEDICINE

Patients who are allergic to certain substances, medications, and so on can avoid the resulting itch if they
2079

Itching

Treatment

IUD

KEY TERMS

Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PERIODICALS

Atopic dermatitis—An intensely itchy inflammation often found on the face of people prone to
allergies. In infants and early childhood, it is called
infantile eczema.
Creeping eruption—Itchy irregular, wandering red
lines on the foot made by burrowing larvae of the
hookworm family and some roundworms.
Dermatitis herpetiformis—A chronic very itchy
skin disease with groups of red lesions that leave
spots behind when they heal. It is sometimes associated with cancer of an internal organ.

Psoriasis—A common, chronic skin disorder that
causes red patches anywhere on the body.
Occasionally, the lesions may itch.
Scabies—A contagious parasitic skin disease characterized by intense itching.

Al-Waili, N. S. ‘‘Topical Application of Natural Honey,
Beeswax and Olive Oil Mixture for Atopic Dermatitis
or Psoriasis: Partially Controlled, Single-Blinded
Study.’’ Complementary Therapies in Medicine 11
(December 2003): 226–234.
Browning, J., B. Combes, and M. J. Mayo. ‘‘Long-Term
Efficacy of Sertraline as a Treatment for Cholestatic
Pruritus in Patients with Primary Biliary Cirrhosis.’’
American Journal of Gastroenterology 98 (December
2003): 2736–2741.
Cavalcanti, A. M., L. M. Rocha, R. Carillo Jr., et al.
‘‘Effects of Homeopathic Treatment on Pruritus of
Haemodialysis Patients: A Randomised PlaceboControlled Double-Blind Trial.’’ Homeopathy 92
(October 2003): 177–181.
Ikoma, A., R. Rukwied, S. Stander, et al. ‘‘Neurophysiology
of Pruritus: Interaction of Itch and Pain.’’ Archives of
Dermatology 139 (November 2003): 1475–1478.
Jones, K. ‘‘Review of Sangre de Drago (Croton lechleri)—A
South American Tree Sap in the Treatment of Diarrhea,
Inflammation, Insect Bites, Viral Infections, and
Wounds: Traditional Uses to Clinical Research.’’
Journal of Alternative and Complementary Medicine
9 (December 2003): 877–896.
Ochoa, J. G. ‘‘Pruritus, a Rare but Troublesome Adverse
Reaction of Topiramate.’’ Seizure 12 (October 2003):
516–518.
Stener-Victorin, E., T. Lundeberg, J. Kowalski, et al.
‘‘Perceptual Matching for Assessment of Itch;
Reliability and Responsiveness Analyzed by a RankInvariant Statistical Method.’’ Journal of Investigative
Dermatology 121 (December 2003): 1301–1305.
Zylicz, Z., M. Krajnik, A. A. Sorge, and M. Costantini.
‘‘Paroxetine in the Treatment of Severe NonDermatological Pruritus: A Randomized, Controlled
Trial.’’ Journal of Pain and Symptom Management
26 (December 2003): 1105–1112.

Swimmer’s itch—An allergic skin inflammation
caused by a sensitivity to flatworms that die under
the skin, causing an itchy rash.

Carol A. Turkington
Rebecca J. Frey, PhD

Eczema—A superficial type of inflammation of the
skin that may be very itchy and weeping in the early
stages; later, the affected skin becomes crusted,
scaly, and thick. There is no known cause.
Hodgkin’s disease—A type of cancer characterized
by a slowly-enlarging lymph tissue; symptoms
include generalized itching.
Lichen planus—A noncancerous, chronic itchy
skin disease that causes small, flat purple plaques
on wrists, forearm, ankles.
Neurodermatitis—An itchy skin disease (also
called lichen simplex chronicus) found in nervous,
anxious people.
Pruriceptors—Nerve endings specialized to perceive itching sensations.
Pruritus—The medical term for itching.

avoid contact with the allergen. Avoiding insect bites,
bee stings, poison ivy and so on can prevent the resulting
itch. Treating sensitive skin carefully, avoiding overdrying of the skin, and protecting against diseases that cause
itchy rashes are all good ways to avoid itching.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Pruritus.’’ Section 10, Chapter 109. In The Merck
2080

IUD
Definition
An IUD is an intrauterine device made of plastic
and/or copper that is inserted into the womb (uterus)
by way of the vaginal canal. One type releases a hormone (progesterone), and is replaced each year. The
second type is made of copper and can be left in place
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
IUDs are used to prevent pregnancy and are considered to be 95-98% effective. It should be noted that
IUDs offer no protection against the acquired immune
deficiency syndrome (AIDS) virus or other sexually
transmitted diseases (STDs).

Precautions
IUDs are placed in the uterus by physicians. Prior
to placement the doctor will take a medical history, do
a physical examination, and take a Pap test. Women
who have had tubal pregnancies, an abnormal Pap
smear, or abnormal vaginal bleeding are generally
disqualified from using this form of contraception.
Also, women who have STDs, an allergy to copper,
severe pain with periods (menstruation), sex with multiple partners, or who are currently pregnant are not
eligible for an IUD. There are no age restrictions.

IUD

for five years. The most common shape in current use
is a plastic ‘‘T’’ which is wrapped with copper wire.

KEY TERMS
Antiseptic—An antiseptic is a chemical that prevents the growth of germs.
Hormone—Hormones are chemicals that are produced in an organ or gland and then are carried by
the blood to another part of the body where they
produce a special effect for which they were designed.
Pap test—This is a procedure by which cells are
collected from the cervix and vagina by inserting a
swab into the vaginal canal. These cells are then
examined under a microscope in order to detect
signs of early cancer.

a local anesthesia is used to reduce any discomfort
associated with the procedure. A plastic string connected to the IUD will hang out of the uterus into the
vagina. The string is used to periodically check the
position of the IUD.

Aftercare
Description
There is continuing controversy over exactly how
IUDs prevent pregnancy. Some researchers think
pregnancy is controlled by preventing conception (fertilization), while others believe that the devices prevent
embryo attachment to the uterine wall (implantation).
IUDs which release a hormone may prevent pregnancy in several ways. Since one hormonal response is a
thickening of the mucous at the entrance to the uterus, it
is more difficult for the sperm to gain entry. This prevents the sperm from reaching an ovum. At the same
time, the lining of the uterus becomes thinner, making it
more difficult for a fertilized egg to implant itself in the
uterus. The copper device slowly releases copper which is
believed to weaken and perhaps kill sperm. An alternate
explanation is that these objects ‘‘sweep’’ the uterus,
dislodging any fertilized egg that attempts to implant
itself. In addition, both devices tend to cause a mild
inflammatory reaction in the lining of the uterus which
also has an adverse impact on implantation.

Preparation
After the physician approves the use of an IUD,
the woman’s genital area is washed thoroughly with
soap and water in preparation of IUD insertion. The
opening into the uterus (cervix) will also be cleaned
with an antiseptic such as an iodine solution. Actual
IUD insertion takes about five minutes, during which
GALE ENCYCLOPEDIA OF MEDICINE

The woman will be taught to watch for the signs and
symptoms of potential complications and how to check
the string, which should be done at least once a week. To
check the string, the woman should first wash her hands
with soap and water. From a squatting position, or with
one foot elevated (such as on a chair), she should gently
insert her finger into the vagina until she nears the cervix.
If she cannot feel the string, if the string feels longer than
it should, or if she can feel part of the IUD, she should
notify her physician immediately. Additional information that needs to be reported includes painful intercourse and unusual discharge from the vagina.

Risks
Serious risks are rare, but include heavy bleeding,
pain, infection, cramps, pelvic inflammatory disease,
perforation of the uterus, and ectopic pregnancy.
Resources
ORGANIZATIONS

Planned Parenthood Federation of America, Inc. 810
Seventh Ave., New York, NY,10019. (800) 669-0156.
<http://www.plannedparenthood.org>.

Donald G. Barstow, RN

Ivory bones see Osteopetroses
Ivy method see Bleeding time
2081

J
Japanese encephalitis
Definition
Japanese encephalitis is an infection of the brain
caused by a virus. The virus is transmitted to humans
by mosquitoes.

Description
The virus that causes Japanese encephalitis is
called an arbovirus, which is an arthropod-borne
virus. Mosquitoes are a type of arthropod.
Mosquitoes in a number of regions carry this virus
and are responsible for passing it along to humans.
Many of these areas are in Asia, including Japan,
Korea, China, India, Thailand, Indonesia, Malaysia,
Vietnam, Taiwan, and the Philippines. Areas where
the disease-causing arbovirus is always present are
referred to as being endemic for the disease. In such
areas, blood tests will reveal that more than 70% of all
adults have been infected at some point with the
arbovirus.
Because the virus that causes Japanese encephalitis is carried by mosquitoes, the number of people
infected increases during those seasons when mosquitoes are abundant. This tends to be in the warmest,
rainiest months. In addition to humans, other animals
like wild birds, pigs, and horses are susceptible to
infection with this arbovirus. Because the specific
type of mosquito carrying the Japanese encephalitis
arbovirus frequently breeds in rice paddies, the disease
is considered to be primarily a rural problem.

Causes and symptoms
The virus is transferred to a human when an
infected mosquito sucks that person’s blood. Once in
the body, the virus travels to various glands where it
multiplies. The virus can then enter the bloodstream.
GALE ENCYCLOPEDIA OF MEDICINE

Ultimately, the virus settles in the brain, where it
causes serious problems.
Japanese encephalitis begins with fever, severe
headache, nausea, and vomiting. As the tissue covering
the brain and spinal cord (the meninges) becomes
infected and swollen, the patient will develop a stiff
and painful neck. By day two or three, the patient
begins to suffer the effects of swelling in the brain.
These effects include:


Problems with balance and coordination



Paralysis of some muscle groups



Tremors



Seizures



Lapses in consciousness



A stiff, mask-like appearance of the face.

The patient becomes dehydrated and loses weight.
If the patient survives the illness, the fever will decrease
by about day seven and the symptoms will begin to
improve by about day 14. Other patients will continue
to have extremely high fevers and their symptoms will
get worse. In these cases, coma and then death occur in
7-14 days. Many patients who recover have permanent
disabilities due to brain damage.

Diagnosis
Most diagnostic techniques for Japanese encephalitis do not yield results very quickly. The diagnosis is
made primarily on the basis of the patient’s symptoms
and the knowledge of the kinds of illnesses endemic to
a particular geographic region.
Immunofluorescence tests, where special viral markers react with human antibodies that have been
tagged with a fluorescent chemical, are used to verify
the disease. However, these results tend to be unavailable until week two of the infection. Other tests involve
comparing the presence and quantity of particular
2083

Jaundice

KEY TERMS
Antibody—A type of cell made by the immune
system that has the ability to recognize markers
(antigens) on the surface of invading organisms,
like bacteria and viruses.
Encephalitis—A swelling of the brain, potentially
causing serious brain damage.
Endemic—Naturally and consistently present in a
certain geographical region.

antibodies in the blood or spinal fluid during week one
with those present during week two of the illness.

in areas where the disease is endemic. Travelers to
these regions can also receive the vaccine.
Controlling the mosquito population with insecticides is another preventive measure. Visitors to
regions with high rates of Japanese encephalitis should
take precautions (like using mosquito repellents and
sleeping under a bed net) to avoid contact with
mosquitoes.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Treatment
There are no treatments available to stop or slow
the progression of Japanese encephalitis. Only the
symptoms of each patient can be treated. Fluids are
given to decrease dehydration and medications are given
to decrease fever and pain. Medications are available to
attempt to decrease brain swelling. Patients in a coma
may require mechanical assistance with breathing.

Prognosis
While the majority of people infected with arbovirus never become sick, those who develop Japanese
encephalitis become very ill. Some outbreaks have a
50% death rate. A variety of long-term problems may
haunt those who recover from the illness. These problems include:


Movement difficulties where the arms, legs, or body
jerks or writhes involuntarily



Shaking



Paralysis



Inability to control emotions



Loss of mental abilities



Mental disturbances, including schizophrenia (which
may affect as many as 75% of Japanese encephalitis
survivors).

Young children are most likely to have serious,
long-term problems after an infection.

Prevention
A three-dose vaccine is available for Japanese
encephalitis and is commonly given to young children
2084

Jaundice
Definition
Jaundice is a condition in which a person’s skin
and the whites of the eyes are discolored yellow due to
an increased level of bile pigments in the blood resulting from liver disease. Jaundice is sometimes called
icterus, from a Greek word for the condition.

Description
In order to understand jaundice, it is useful to
know about the role of the liver in producing bile.
The most important function of the liver is the processing of chemical waste products like cholesterol and
excreting them into the intestines as bile. The liver is
the premier chemical factory in the body—most
incoming and outgoing chemicals pass through it. It
is the first stop for all nutrients, toxins, and drugs
absorbed by the digestive tract. The liver also collects
chemicals from the blood for processing. Many of
these outward-bound chemicals are excreted into the
bile. One particular substance, bilirubin, is yellow.
Bilirubin is a product of the breakdown of hemoglobin, which is the protein inside red blood cells.
If bilirubin cannot leave the body, it accumulates
and discolors other tissues. The normal total level
of bilirubin in blood serum is between 0.2 mg/dL
and 1.2 mg/dL. When it rises to 3 mg/dL or higher,
the person’s skin and the whites of the eyes become
noticeably yellow.
GALE ENCYCLOPEDIA OF MEDICINE

the intermittent symptoms of the disease. When
enough cells burst at once, jaundice may result
from the large amount of bilirubin formed from the
hemoglobin in the dead cells. The pigment may reach
the urine in sufficient quantities to cause ‘‘blackwater
fever,’’ an often lethal form of malaria.


Side effects of certain drugs. Some common drugs
can cause hemolysis as a rare but sudden side effect.
These medications include some antibiotic and antituberculosis medicines; drugs that regulate the heartbeat; and levodopa, a drug used to treat Parkinson’s
disease.



Certain drugs in combination with a hereditary
enzyme deficiency known as glucose-6-phosphate
dehydrogenase (G6PD). G6PD is a deficiency that
affects more than 200 million people in the world.
Some of the drugs listed above are more likely to
cause hemolysis in people with G6PD. Other drugs
cause hemolysis only in people with this disorder.
Most important among these drugs are anti-malarial
medications such as quinine, and vitamins C and K.



Poisons. Snake and spider venom, certain bacterial
toxins, copper, and some organic industrial chemicals directly attack the membranes of red blood cells.



Artificial heart valves. The inflexible moving parts of
heart valves damage RBCs as they flutter back and
forth. This damage is one reason to recommend pig
valves and valves made of other organic materials.



Hereditary RBC disorders. There are a number of
hereditary defects that affect the blood cells. There
are many genetic mutations that affect the hemoglobin itself, the best-known of which is sickle cell disease. Such hereditary disorders as spherocytosis
weaken the outer membrane of the red cell. There
are also inherited defects that involve the internal
chemistry of RBCs.



Enlargement of the spleen. The spleen is an organ
that is located near the upper end of the stomach and
filters the blood. It is supposed to filter out and
destroy only worn-out RBCs. If it has become
enlarged, it filters out normal cells as well. Malaria,
other infections, cancers and leukemias, some of the
hereditary anemias mentioned above, obstruction of
blood flow from the spleen–all these and many more
diseases can enlarge the spleen to the point where it
removes too many red blood cells.



Diseases of the small blood vessels. Hemolysis that
occurs in diseased small blood vessels is called microangiopathic hemolysis. It results from damage
caused by rough surfaces on the inside of the capillaries. The RBCs squeeze through capillaries one at a

Causes and symptoms
There are many different causes for jaundice, but
they can be divided into three categories based on
where they start–before, in, or after the liver (prehepatic, hepatic and post-hepatic). When bilirubin
begins its life cycle, it cannot be dissolved in water.
The liver changes it so that it is soluble in water. These
two types of bilirubin are called unconjugated (insoluble) and conjugated (soluble). Blood tests can easily
distinguish between these two types of bilirubin.
Hemoglobin and bilirubin formation
Bilirubin begins as hemoglobin in the blood-forming organs, primarily the bone marrow. If the production of red blood cells (RBCs) falls below normal, the
extra hemoglobin finds its way into the bilirubin cycle
and adds to the pool.
Once hemoglobin is in the red cells of the blood, it
circulates for the life span of those cells. The hemoglobin that is released when the cells die is turned into
bilirubin. If for any reason the RBCs die at a faster
rate than usual, bilirubin can accumulate in the blood
and cause jaundice.
Hemolytic disorders
Many disorders speed up the death of red blood
cells. The process of red blood cell destruction is called
hemolysis, and the diseases that cause it are called
hemolytic disorders. If red blood cells are destroyed
faster than they can be produced, the patient develops
anemia. Hemolysis can occur in a number of diseases,
disorders, conditions, and medical procedures:


Malaria. The malaria parasite develops inside red
blood cells. When it is mature it breaks the cell
apart and swims off in the blood. This process happens to most of the parasites simultaneously, causing

GALE ENCYCLOPEDIA OF MEDICINE

2085

Jaundice

Bile is formed in the liver. It then passes into the
network of hepatic bile ducts, which join to form a
single tube. A branch of this tube carries bile to the
gallbladder, where it is stored, concentrated, and
released on a signal from the stomach. Food entering
the stomach is the signal that stimulates the gallbladder to release the bile. The tube, which is called the
common bile duct, continues to the intestines. Before
the common bile duct reaches the intestines, it is joined
by another duct from the pancreas. The bile and the
pancreatic juice enter the intestine through a valve
called the ampulla of Vater. After entering the intestine, the bile and pancreatic secretions together help in
the process of digestion.

Jaundice

time and can easily be damaged by scraping against
the vessel walls.


Immune reactions to RBCs. Several types of cancer
and immune system diseases produce antibodies that
react with RBCs and destroy them. In 75% of cases,
this reaction occurs all by itself, with no underlying
disease to account for it.



Transfusions. If a patient is given an incompatible
blood type, hemolysis results.



Kidney failure and other serious diseases. Several
diseases are characterized by defective blood coagulation that can destroy red blood cells.



Erythroblastosis fetalis. Erythroblastosis fetalis is a
disease of newborns marked by the presence of too
many immature red blood cells (erythroblasts) in the
baby’s blood. When a baby’s mother has a different
blood type, antibodies from the mother may leak
into the baby’s circulation and destroy blood cells.
This reaction can produce severe hemolysis and jaundice in the newborn. Rh factor incompatibility is the
most common cause.



High bilirubin levels in newborns. Even in the
absence of blood type incompatibility, the newborn’s
bilirubin level may reach threatening levels.
Normal jaundice in newborns

Normal newborn jaundice is the result of two
conditions occurring at the same time–a pre-hepatic
and a hepatic source of excess bilirubin. First of all, the
baby at birth immediately begins converting hemoglobin from a fetal type to an adult type. The fetal type of
hemoglobin was able to extract oxygen from the lower
levels of oxygen in the mother’s blood. At birth the
infant can extract oxygen directly from his or her own
lungs and does not need the fetal hemoglobin any
more. So fetal hemoglobin is removed from the system
and replaced with adult hemoglobin. The resulting
bilirubin loads the system and places demands on the
liver to clear it. But the liver is not quite ready for the
task, so there is a period of a week or so when the liver
has to catch up. During that time the baby is
jaundiced.
Hepatic jaundice
Liver diseases of all kinds threaten the organ’s
ability to keep up with bilirubin processing. Starvation, circulating infections, certain medications, hepatitis, and cirrhosis can all cause hepatic jaundice, as
can certain hereditary defects of liver chemistry,
including Gilbert’s syndrome and Crigler-Najjar
syndrome.
2086

This patient suffers from obstructive jaundice, which is often
caused by gallstones. (Custom Medical Stock Photo.
Reproduced by permission.)

Post-hepatic jaundice
Post-hepatic forms of jaundice include the jaundices caused by failure of soluble bilirubin to reach the
intestines after it has left the liver. These disorders are
called obstructive jaundices. The most common cause
of obstructive jaundice is the presence of gallstones in
the ducts of the biliary system. Other causes have to do
with birth defects and infections that damage the bile
ducts; drugs; infections; cancers; and physical injury.
Some drugs–and pregnancy on rare occasions–simply
cause the bile in the ducts to stop flowing.
Symptoms and complications associated with
jaundice
Certain chemicals in bile may cause itching when
too much of them end up in the skin. In newborns,
insoluble bilirubin may get into the brain and do permanent damage. Long-standing jaundice may upset
GALE ENCYCLOPEDIA OF MEDICINE

Jaundice

the balance of chemicals in the bile and cause stones to
form. Apart from these potential complications and
the discoloration of skin and eyes, jaundice by itself is
inoffensive. Other symptoms are determined by the
disease producing the jaundice.

Diagnosis
Physical examination
In many cases the diagnosis of jaundice is suggested by the appearance of the patient’s eyes and
complexion. The doctor will ask the patient to lie flat
on the examining table in order to feel (palpate) the
liver and spleen for enlargement and to evaluate any
abdominal pain. The location and severity of abdominal pain and the presence or absence of fever help the
doctor to distinguish between hepatic and obstructive
jaundice.
Laboratory tests
Disorders of blood formation can be diagnosed by
more thorough examination of the blood or the bone
marrow, where blood is made. Occasionally a bone
marrow biopsy is required, but usually the blood itself
will reveal the diagnosis. The spleen can be evaluated
by an ultrasound examination or a nuclear scan if the
physical examination has not yielded enough
information.
Liver disease is usually assessed from blood studies alone, but again a biopsy may be necessary to
clarify less obvious conditions. A liver biopsy is performed at the bedside. The doctor uses a thin needle to
take a tiny core of tissue from the liver. The tissue
sample is sent to the laboratory for examination
under a microscope.
Assessment of jaundice in newborns
Newborns are more likely to have problems with
jaundice if:


They are premature.



They are Asian or Native Americans.



They have been bruised during the birth process.



They have lost too much weight during the first few
days.



They are born at high altitude.



The mother has diabetes.



Labor had to be induced.

In 2003, research was continuing to find noninvasive methods to determine bilirubin levels in newborns
GALE ENCYCLOPEDIA OF MEDICINE

A newborn baby undergoes phototherapy with visible blue
light to treat his jaundice. (Photograph by Ron Sutherland,
Photo Researchers, Inc. Reproduced by permission.)

so that physicians did not have to rely on visual examination alone to determine which infants should
receive blood tests. Once these measurements of skin
pigment can be shown effective and cost-effective in
clinical practice, they may become more available.
Another study used this measurement method incorporated into home health visits to monitor babies
within 24 hours of discharge from the hospital following birth.
Imaging studies
Disease in the biliary system can be identified by
imaging techniques, of which there are many. X rays
are taken a day after swallowing a contrast agent that
is secreted into the bile. This study gives functional as
well as anatomical information. There are several
ways of injecting contrast dye directly into the bile
ducts. It can be done through a thin needle pushed
2087

Jaundice

straight into the liver or through a scope passed
through the stomach that can inject dye into the
Ampulla of Vater. CT and MRI scans are very useful
for imaging certain conditions like cancers in and
around the liver or gallstones in the common bile duct.

Treatment
Jaundice in newborns
Newborns are the only major category of patients
in whom the jaundice itself requires attention. Because
the insoluble bilirubin can get into the brain, the amount
in the blood must not go over certain levels. If there is
reason to suspect increased hemolysis in the newborn,
the bilirubin level must be measured repeatedly during
the first few days of life. If the level of bilirubin shortly
after birth threatens to go too high, treatment must
begin immediately. Exchanging most of the baby’s
blood was the only way to reduce the amount of bilirubin until a few decades ago. Then it was discovered
that bright blue light rendered the bilirubin harmless.
Now jaundiced babies are fitted with eye protection and
placed under bright fluorescent lights. The light chemically alters the bilirubin in the blood as it passes through
the baby’s skin. In 2003, researchers were testing a new
drug called Stanate that showed promise in blocking
bilirubin production. However, debate concerning the
use of the drug for treatment of only those infants with
jaundice or as a preventive measure was delaying its
FDA approval and widespread use.
Hemolytic disorders
Hemolytic diseases are treated, if at all, with medications and blood transfusions, except in the case of a
large spleen. Surgical removal of the spleen (splenectomy) can sometimes cure hemolytic anemia. Drugs that
cause hemolysis or arrest the flow of bile must be
stopped immediately.
Hepatic jaundice
Most liver diseases have no specific cure, but the
liver is so robust that it can heal from severe damage
and regenerate itself from a small remnant of its original tissue.

KEY TERMS
Ampulla of Vater—The widened portion of the
duct through which the bile and pancreatic juices
enter the intestine. Ampulla is a Latin word for a
bottle with a narrow neck that opens into a wide
body.
Anemia—A condition in which the blood does not
contain enough hemoglobin.
Biliary system/Bile ducts—The gall bladder and
the system of tubes that carries bile from the liver
into the intestines.
Bilirubin—A reddish pigment excreted by the liver
into the bile as a breakdown product of
hemoglobin.
Crigler-Najjar syndrome—A moderate to severe
form of hereditary jaundice.
Erythroblastosis fetalis—A disorder of newborn
infants marked by a high level of immature red
blood cells (erythroblasts) in the infant’s blood.
Gilbert’s syndrome—A mild hereditary form of
jaundice.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency—A hereditary disorder that can lead to
episodes of hemolytic anemia in combination
with certain medications.
Hemoglobin—The red chemical in blood cells that
carries oxygen.
Hemolysis—The destruction or breakdown of red
blood cells.
Hepatic—Refers to the liver.
Icterus—Another name for jaundice.
Microangiopathic—Pertaining to disorders of the
small blood vessels.
Pancreas—The organ beneath the stomach that
produces digestive juices, insulin, and other
hormones.
Sickle cell disease—A hereditary defect in hemoglobin synthesis that changes the shape of red cells
and makes them more fragile.
Splenectomy—Surgical removal of the spleen.

Post-hepatic jaundice
Obstructive jaundice frequently requires a surgical cure. If the original passageways cannot be
restored, surgeons have several ways to create alternate routes. A popular technique is to sew an open
piece of intestine over a bare patch of liver. Tiny bile
ducts in that part of the liver will begin to discharge
2088

their bile into the intestine, and pressure from the
obstructed ducts elsewhere will find release in that
direction. As the flow increases, the ducts grow to
accommodate it. Soon all the bile is redirected through
the open pathways.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose

Erythroblastosis fetalis can be prevented by
giving an Rh negative mother a gamma globulin solution called RhoGAM whenever there is a possibility
that she is developing antibodies to her baby’s blood.
G6PD hemolysis can be prevented by testing patients
before giving them drugs that can cause it. Medication
side effects can be minimized by early detection and
immediate cessation of the drug. Malaria can often be
prevented by certain precautions when traveling in
tropical or subtropical countries. These precautions
include staying in after dark; using prophylactic
drugs such as mefloquine; and protecting sleeping
quarters with mosquito nets treated with insecticides
and mosquito repellents. In 2003, new studies showed
promise for a possible vaccine against malaria. Early
trials showed that vaccination combination might stimulate T-cell activity against malaria, the best type of
protection that researchers can hope to find. However,
further studies will have to be done.

Sports injuries, automobile accidents, falls, or fistfights are a few of the situations where the jaw might
be fractured or broken. In these cases, jaw wiring may
be necessary to keep the bones aligned and stable while
the jaw heals. The presence of cancer or other diseased
tissues may make removal and reconstruction of the
jaw necessary. Wiring the jaws shut has been used in
the past as a weight loss aid in cases of extreme obesity
where other treatments had failed, although this procedure is rarely used for that purpose today.

Resources

Jaw wiring surgery can be performed by an oral or
maxillofacial surgeon (a specially trained dentist), or
by an otolaryngologist (a doctor specializing in surgeries of the head and neck). The procedure may be
done in a medical or dental office if the office is staffed
and equipped to handle this type of surgery. More
often, this surgery is performed in a hospital or medical center surgical area. If jaw wiring is required due
to an injury, the surgeon may set the fracture immediately before swelling sets in. It is also possible to wait
(up to several weeks) until the swelling goes down and
some of the soft tissue injuries have healed, prior to
wiring the jaw fracture.

PERIODICALS

Grimm, David. ‘‘Baby Pigment Peril.’’ U.S. News &World
Report July 28, 2003: 39.
Lawrence, David. ‘‘Combination Malaria Vaccine Shows
Early Promise in Human Trials.’’ The Lancet May 31,
2003: 1875.
Morantz, Carrie, and Brian Torrey. ‘‘AHRQ Report on
Neonatal Jaundice.’’ American Family Physician June 1,
2003: 2417.
Richmond, Glenn, Melissa Brown, and Patricia Wagstaff.
‘‘Using a Home Care Model to Monitor Bilirubin
Levels in Early Discharged Infants.’’ Topics in Health
Information Management January–March 2003: 39–43.
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://www.
liverfoundation.org>.

J. Ricker Polsdorfer, MD
Teresa G. Odle

Jaw wiring
Definition
Jaw wiring, also known as maxillomandibular
fixation, is a surgical procedure where metal pins and
wires are anchored into the jaw bones and surrounding tissues to keep the jaw from moving.
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Traumatic injuries to the face can cause damage to
facial nerves and salivary glands and ducts. These
injuries can also leave scars that may require additional surgery to correct.

Description

The surgeon realigns the fractured bones. Every
effort is made to restore the shape and appearance of
the original jaw line. If any teeth were damaged, repair
or replacement may be done at the same time. Small
incisions may be made through the skin and surrounding tissue so the pins and wires can be set into the
jawbone to hold the fracture together. To prevent the
lower jaw from moving during healing, pins and wires
may be inserted into the top jaw, as well. The upper
and lower jaws are then wired together in order to
stabilize the fracture.
As with other types of bone fractures, the jaw may
take several weeks to heal. Another type of jaw immobilization that has been developed more recently, rigid
fixation uses small metal plates and screws rather than
pins and wires to secure the jaw bones. The main
benefit of this technique is that the jaws do not have
to be wired shut, allowing the patient to return to a
more normal lifestyle sooner.
2089

Jaw wiring

Prevention

Jet lag

KEY TERMS

American Dental Association. 211 E. Chicago Ave., Chicago,
IL 60611. (312) 440-2500. <http://www.ada.org>.
OTHER

Oral and maxillofacial surgeon—A dentist who is
trained to perform surgery to correct injuries,
defects, or conditions of the mouth, teeth, jaws,
and face.
Otolaryngologist—A doctor who is trained to treat
injuries, defects, or conditions of the head and
neck.

‘‘Know the Score on Facial Sports Injuries’’ The Virtual Hospital
Page. University of Iowa. <http://www.vh.org>.
‘‘Topic: Maxillofacial Trauma.’’ Connecticut Maxillofacial
Surgeons Page. <http://www.cmsllc.com/toptrm.html>.

Altha Roberts Edgren

JC virus infection see Progressive multifocal
leukoencephalopathy
Preparation
X rays of the fractured area may be taken prior to
surgery. Depending on the extent of the facial injury or
condition to be corrected, the patient may receive a
sedative for relaxation, a local anesthetic drug to
numb the area, and/or an anesthetic agent to induce
unconsciousness prior to the surgery.

Aftercare
A patient whose jaw has been wired will not be
able to eat solid foods for several weeks. In order for
the bone and surrounding tissues to heal, it is important to maintain adequate nutrition. A liquid diet that
can be consumed through a straw, will be required.
Soft, precooked foods can be liquefied in a blender,
however, it may be difficult for the patient to consume
adequate calories, protein, vitamins, and minerals with
this type of diet. Liquid diet formulas may be a good
alternative. The patient will also have to be taught how
to care for the mouth, teeth, and injured area while the
wires are in place.

Risks
It is possible that scarring may occur due to the
need to make small incisions in the skin in order to
insert the wires. With any surgical procedure, there are
risks associated with the anesthetic drugs used and the
possibility of infection. If there is a risk that the patient
may vomit, the jaw wiring may pose a choking hazard.
It may be recommended that wire cutters be kept
available in case the wires need to be cut in an emergency situation.
Resources
ORGANIZATIONS

American Association of Oral & Maxillofacial Surgeons.
9700 West Bryn Mawr Avenue; Rosemont, IL
60018-5701; (847) 678-6200.
2090

Jejunostomy see Enterostomy

Jet lag
Definition
Jet lag is a condition marked by fatigue, insomnia, and irritability that is caused by air travel
through changing time zones. It is commonplace: a
2002 study of international business travelers (IBTs)
found that jet lag was one of the most common
health problems reported, affecting as many as
74% of IBTs.

Description
Living organisms are accustomed to periods of
night and day alternating at set intervals. Most of the
human body’s regulating hormones follow this cycle,
known as circadian rhythm. The word circadian
comes from the Latin, circa, meaning about, and
dies, meaning day. These cycles are not exactly 24
hours long, hence the ‘‘circa.’’ Each chemical has its
own cycle of highs and lows, interacting with and
influencing the other cycles. Body temperature, sleepiness, thyroid function, growth hormone, metabolic
processes, adrenal hormones, and the sleep hormone
melatonin all cycle with daylight. There is a direct
connection between the retina (where light hits the
back of the eye) and the part of the brain that controls
all these hormones. Artificial light has some effect, but
sunlight has much more.
When people are without clocks in a compartment
that is completely closed to sunlight, most of them fall
into a circadian cycle of about 25 hours. Normally, all
the regulating chemicals follow one another in order
like threads in a weaving pattern. Every morning
the sunlight resets the cycle, stimulating the leading
GALE ENCYCLOPEDIA OF MEDICINE

When traveling through a number of time zones,
most people reset their rhythms within a few days,
demonstrating the adaptability of the human species.
Some people, however, have upset rhythms that last
indefinitely.

Another new area of research involves the genes
that encode the proteins governing circadian rhythms.
It is known as of late 2002 that differences among
individuals in adaptability to time zone changes are
to some extent genetically determined. Targeting the
genes that affect this adaptability may yield new treatments for jet lag and other disorders of circadian
rhythm.

Alternative treatment

Causes and symptoms
Traveling through a few time zones at a time is not
as disruptive to circadian rhythms as traveling around
the world can be. The foremost symptom of jet lag is
altered sleep pattern—sleepiness during the day, and
insomnia during the night. Jet lag may also include
indigestion and trouble concentrating. Individuals
afflicted by jet lag will alternate in and out of a normal
day-night cycle.

Treatment
Current treatments
In cases of short-term insomnia triggered by jet
lag, a physician may recommend sleeping pills or
prescription medication. Such medication should
only be taken under the guidance of a health care
professional.
Investigational treatments
In 2002, a team from Flanders University
invented new jet lag sunglasses equipped with a vision
device that used light to stimulate travelers brains.
They believed that wearing the glasses before and
during flights could help the human clock adjust
more easily to changing time zones. The researchers
were looking for a commercial partner to help them
further study the glasses and make them widely available. The effectiveness of glasses or other headmounted light devices is still uncertain, however. A
team of researchers at Columbia University reported
in the fall of 2002 that the use of a head-mounted light
visor yielded only modest improvement in the test
subjects’ symptoms of jet lag.
A newer medication that is considered investigational is a melatonin agonist presently known as LY
156735. An agonist is a drug that stimulates activity at
cell receptors that are normally stimulated by such
naturally occurring substances as melatonin. LY
156735 was found to speed up the readaptation time
of volunteer subjects following a simulated 9-hour
time shift.
GALE ENCYCLOPEDIA OF MEDICINE

Exposure to bright morning sunlight cures jet lag
after a few days in most people. A few will have
prolonged sleep phase difficulties. For these, there is
a curious treatment that has achieved success. By forcing one’s self into a 27 hour day, complete with the
appropriate stimulation from bright light, all the
errant chemical cycles will be able to catch up during
one week.
When selecting an international flight, individuals
should try to arrange an early evening arrival in their
destination city. When an individual is traveling to a
destination in the east, he or she can try going to bed
and waking up a few hours earlier several days before
their flight. If travel is to the west, going to bed and
waking up later than usual can help the body start to
adjust to the upcoming time change. More specific
recommendations are available as of 2002, tailored
to whether the person is traveling through six time
zones, 7–9 zones, or 10 or more.
The following precautions taken during an international flight can help to limit or prevent jet lag:


Stay hydrated. Drink plenty of water and juices
to prevent dehydration. Beverages and foods with
caffeine should be avoided because of their stimulant
properties. Alcohol should also be avoided.



Stretch and walk. As much movement as possible
during a flight helps circulation, which moves nutrients and waste through the body and aids in
elimination.



Stay on time. Set watches and clocks ahead to the
time in the destination city to start adjusting to the
change.



Sleep smart. Draw the shade and sleep during the evening hours in the destination city, even if it is still daylight outside of the airplane. Earplugs and sleep masks
may be helpful in blocking noise and light. Many
airlines provide these items on international flights.



Dress comfortably. Wear or bring comfortable
clothes and slippers that will make sleeping during
the flight easier.
2091

Jet lag

chemicals and thus compensating for the difference
between the 24-hour day and the 25-hour innate
rhythm.

Jet lag

KEY TERMS
Agonist—A medication that has an affinity for and
stimulates the activity of cell receptors that are
normally stimulated by naturally occurring substances, including melatonin.
Circadian—Pertaining to biological rhythms
occurring at approximately 24-hour intervals. Jet
lag is caused by a disruption of the human body’s
circadian clock.
Hormone—A chemical made in one part of the
body that has an effect on another part.
Melatonin—A hormone that helps to regulate circadian rhythms.

Once arriving in their destination city, individuals
should spend as much time outdoors in the sunlight as
possible during the day to reset their internal clock and
lessen the symptoms of jet lag. Bedtime should be
postponed until at least 10 P.M., with no daytime
naps. If a daytime nap is absolutely necessary, it
should be limited to no more than two hours.
To promote a restful sleeping environment in a
hotel setting, individuals should request that the hotel
desk hold all phone calls. Because sleeping in too late
can also prolong jet lag, an early wake up call should
be requested if an alarm clock is not available. If the
hotel room is noisy, a portable white noise machine
can help to block outside traffic and hallway noises.
A room air conditioner or fan can serve the same
purpose. The temperature in the room should also be
adjusted for sleeping comfort.
All antioxidants help to decrease the effects of jet
lag. Extra doses of vitamins A, C, and E, as well as zinc
and selenium, two days before and two days after a
flight help to alleviate jet lag. Melatonin, a hormone
which helps to regulate circadian rhythms, can also
help to combat jet lag. Melatonin is available as an
over-the-counter supplement in most health food
stores and pharmacies, but no more than 3 mg should
be used in a 24-hour period.
If weather prevents an individual from spending
time in the sunlight, light therapy may be beneficial in
decreasing jet lag symptoms. Light therapy, or phototherapy, uses a device called a light box, which contains a set of fluorescent or incandescent lights in front
of a reflector. Typically, the patient sits for 30 minutes
next to a 10,000-lux box (which is about 50 times as
bright as an ordinary indoor light). Light therapy is
2092

safe for most people, but those with eye diseases
should consult a healthcare professional before undergoing the treatment.

Prognosis
Jet lag usually lasts 24–48 hours after travel has
taken place. In that short time period, the body adjusts
to the time change, and with enough rest and daytime
exposure to sunlight, it returns to normal circadian
rhythm.

Prevention
Eating a high protein diet that is low in calories
before intended travel may help reduce the effects of
jet lag.
Resources
PERIODICALS

Boulos, Z., M. M. Macchi, M. P. Sturchler, et al. ‘‘Light
Visor Treatment for Jet Lag After Westward Travel
Across Six Time Zones.’’ Aviation, Space, and
Environmental Medicine 73 (October 2002): 953–963.
‘‘Jet Lag Sunglasses Help Body Clock Tick.’’ Optician
August 2, 2002: 1.
Monson, Nancy. ‘‘What Really Works for Jet Lag.’’ Shape
August 2002: 78.
Nickelsen, T., A. Samel, M. Vejvoda, et al. ‘‘Chronobiotic
Effects of the Melatonin Agonist LY 156735 Following
a Simulated 9h Time Shift: Results of a Placebo-Controlled
Trial.’’ Chronobiology International 19 (September 2002):
915–936.
Parry, B. L. ‘‘Jet Lag: Minimizing Its Effects with Critically
Timed Bright Light and Melatonin Administration.’’
Journal of Molecular Microbiology and Biotechnology 4
(September 2002): 463–466.
Rogers, H. L., and S. M. Reilly. ‘‘A Survey of the Health
Experiences of International Business Travelers. Part
One—Physiological Aspects.’’ Journal of the American
Association of Occupational Health Nurses 50 (October
2002): 449–459.
Wisor, J. P. ‘‘Disorders of the Circadian Clock: Etiology and
Possible Therapeutic Targets.’’ Current Drug Targets:
Cns and Neurological Disorders 1 (December 2002):
555–566.
ORGANIZATIONS

American Sleep Disorders Association. 1610 14th Street
NW, Suite 300. Rochester, MN 55901. (507) 287–6006.
National Sleep Foundation. 1367 Connecticut Avenue NW,
Suite 200. Washington, DC 20036. (202) 785–2300.

Paula Anne Ford-Martin
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition

Fungus—A single-celled or multi-celled organism
without chlorophyll that reproduces by spores and
lives by absorbing nutrients from organic matter.
Scrotum—The external pouch of skin and muscle
containing the testes (testicles).

Also known as Tinea cruris, jock itch is a growth
of fungus in the warm, moist area of the groin.

Description
Although there are many causes of jock itch,
this term has become synonymous with tinea cruris,
a common fungal infection that affects the groin
and inner thighs of men and woman. Tinea is the
name of the fungus; cruris comes from the Latin
word for leg. Jock itch can develop when tight
garments trap moisture and heat. This creates an
environment in which fungi multiply and flourish.
Athletes often get jock itch but non-athletic men
who sweat a lot can also get it. Jock itch occurs
more commonly in men, but can affect women as
well. The jock itch fungus may cause a rash on the
upper and inner thighs, the armpits, and the area
just underneath the breasts. Many people with tinea
cruris also have athlete’s foot. Athlete’s foot is
called tinea pedis.

Causes & symptoms
The rash of jock itch starts in the groin fold
usually on both sides. If the rash advances, it usually
advances down the inner thigh. The advancing edge is
redder and more raised than areas that have been
infected longer. The advancing edge is usually scaly
and very easily distinguished or well demarcated. The
skin within the border turns a reddish-brown and
loses much of its scale. Jock itch can spread to the
pubic and genital regions and sometimes to the
buttocks.
Jock itch caused by T. rubrum does not involve the
scrotum or penis. If those areas are involved, the most
likely agent is Candida albicans, the same type of yeast
that causes vaginal yeast infections.

Vaginal yeast infection—An overgrowth of fungus
in the vaginal area.

Treatment
Typical conventional treatment for jock itch
involves the use of an anti-fungal cream, spray, or
powder twice a day for about two weeks. Three commonly used, over-the-counter anti-fungals are miconazole (Micatin), clotrimazole (Lotrimin) and tolnaftate
(Tinactin). While the tendency to discontinue treatment
once itching disappears is common, it is important to
use the anti-fungal for a full two-week course in order to
prevent recurrence of the infection.

Alternative treatment
Topical treatments include poultices of peppermint, oregano, or lavender. Tea tree oil, diluted with
a carrier oil of almond oil, can be applied to the rash
several times per day. Cedarwood and jasmine oils can
relieve itching when applied in the same manner.
Grapefruit seed extract can be taken as a strong solution of 15 drops in 1 oz of water.
Another alternative remedy for jock itch is to
wash the groin area with the diluted juice of a freshly
squeezed lemon, which can help dry up the rash.
A hair dryer on the cool setting can also be used on
the area after showering to dry it thoroughly. A warm
bath relieves itching in many patients. The affected
area should kept clean and dry, and loose-fitting, cotton underwear is recommended.

Prognosis
Diagnosis
Often a case of jock itch can be identified based on
the characteristic description previously described. If
assessed by a conventional doctor, the area of affected
skin may be scraped onto a glass slide for definitive
diagnosis under the microscope. In order to determine
the exact type of fungus present, a small piece of
affected skin maybe sent off to the lab for further
study.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment for jock itch is quick and usually effective, but the condition often comes back. With treatment, jock itch improves in two or three days and is
completely gone in three or four weeks. The following
people should be especially vigilant to prevent the
problem from returning:


Athletes



People with fungal infections that affect other parts
of the body (such as athlete’s foot)
2093

Jock itch

KEY TERMS

Jock itch

Joint biopsy



People who wear tight clothing



People with damaged or altered immune systems,
including people with HIV or AIDS

Prevention
The best prevention of jock itch is cleanliness and
sanitation. This includes keeping the groin area dry,
wearing loose-fitting rather than tight clothing, wear
boxer shorts rather than briefs, change sweat-covered
clothes as soon as possible, showering immediately
after working out or playing a sport and then applying
talc, and washing workout clothes or sports uniforms
after each use.
Resources
BOOKS

Icon Health Publications. Jock Itch—A Medical Dictionary,
Bibliography, and Annotated Research Guide to Internet
References San Diego: Icon Health Publications, 2003.
PERIODICALS

Grin, Caron. ‘‘Tinea: Diagnostic Clues, Treatment Keys.’’
Consultant (February 2004): 214-216.
‘‘Jock Itch.’’ Clinical Reference Systems (January 1,
2004): 1859.
Schmitt, B. D. ‘‘Jock Itch for Teenagers.’’ Clinical Reference
Systems (January 1, 2004): 1858.

Joint—The point where two bones meet.
Pathology—The branch of medicine that looks at
abnormal changes in cells and tissues which signal
disease.
Synovial membrane—Membrane lining a joint.
Trocar—A sharp pointed tube through which a
needle can be inserted.

Purpose
A joint biopsy is performed to determine why a
joint is painful or swollen. It is usually reserved for
more difficult cases where the diagnosis is not clear.
The test can be used to diagnose bacterial or fungal
infections, an abnormal buildup of iron, cancer, or
other diseases.

Precautions
The procedure must be done under very sterile
conditions to reduce the risk of infection.

Description

ORGANIZATIONS

American Academy of Dermatology. 1350 I St. NW, Suite
870, Washington, DC 20005. (202) 842-3555. <http://
www.aad.org>.
OTHER

August 5, 2003. National Institutes of Health Medical
Encyclopedia Jock Itch <http://www.nlm.nih.gov/
medlineplus/print/ency/article/ooo876.htm>.
(Accessed March 30, 2005).

Ken R. Wells,

Jock itch see Ringworm
Joint aspiration see Joint fluid analysis

Joint biopsy
Definition
A joint or synovial membrane biopsy refers to a
procedure where a sample of the joint lining or synovial membrane is taken.
2094

KEY TERMS

The test is performed either in the doctor’s office,
clinic, or hospital by a surgeon. There are many different ways to perform this biopsy: through an incision in the joint; with a scope inserted in the joint; or,
more typically, by the insertion of a sharp instrument
through the skin. The procedure can be taken from
any joint, but the most common joint requiring biopsy
is the knee. A sharp instrument (trocar) is pushed into
the joint space. A needle with an attached syringe is
inserted into the joint to withdraw fluid for laboratory
analysis. The surgeon may instill numbing medicine
into the joint and along the needle track before the
needle is withdrawn. The trocar and then the biopsy
needle is inserted and specimens taken. After the specimen is taken, both the trocar and the biopsy needle are
removed, a bandage is placed over the joint, and the
samples are sent to pathology for analysis.

Preparation
Blood tests will be done to check that blood clots
properly. A mild sedative may be given before the
procedure. With the patient lying down, the skin
over the joint is disinfected and a local anesthetic is
injected into the skin and tissue just below the skin.
GALE ENCYCLOPEDIA OF MEDICINE

The joint will need rest for at least one day.
Normal activity can resume if there is no increased
pain or swelling.

Risks
There is a chance of joint swelling or tenderness.
Rarely, bleeding and infection can occur in the joint,
or the biopsy needle could break off or strike a nerve
or blood vessel. The risk of infection is higher if the
patient has an immune deficiency.
Resources
BOOKS

Schumacher, H. Ralph, Jr. ‘‘Synovial Fluid Analysis and
Synovial Biopsy.’’ In Textbook of Rheumatology, edited
by William N. Kelley, et al. Philadelphia: W. B.
Saunders Co., 1997.

Jeanine Barone, Physiologist

Joint endoscopy see Arthroscopy

Joint fluid analysis
Definition
Joint fluid analysis, also called synovial fluid analysis, or arthrocentesis, is a procedure used to assess
joint-related abnormalities, such as in the knee or
elbow.

Purpose
The purpose of a joint fluid analysis is to identify
the cause of swelling in the joints, to relieve pain and
distention from fluid accumulation in the joint, and to
diagnose certain types of arthritis and inflammatory
joint diseases. The test is also a method to determine
whether an infection, either bacterial or fungal, exists
within the joint.

Precautions
Joint fluid analysis should not be performed on
any patient who is uncooperative, especially if the
patient cannot or will not keep the joint immobile
throughout the procedure. Patients with certain infections should be excluded from the procedure, particularly those who have a local infection along the
proposed needle track. The joint space should be
GALE ENCYCLOPEDIA OF MEDICINE

accessible. Therefore, a poorly accessible joint space,
such as in hip aspiration in an obese patient, should
not be subject to this procedure.

Description
The test is also called arthrocentesis, joint tap, and
closed joint aspiration. Normal synovial fluid is a clear
or pale-yellow fluid found in small amounts in joints,
bursae (fluid-filled sac found on points of friction, like
joints), and tendon sheaths. The procedure is done by
passing a needle into a joint space and sucking out
(aspirating) synovial fluid for diagnostic analysis.
When the sample is sent to the laboratory, the fluid
is analyzed for color, clarity, quantity, and chemical
composition. It is also examined microscopically to
check for the presence of bacteria and other cells.
The procedure takes about 10 minutes. Prior to
the procedure, any risks that are involved should be
explained to the patient. No intravenous pain medications or sedatives are required, although the patient
will be given a local anesthetic.
The patient is asked to lie on their back and
remain relaxed. The local anesthetic, typically an
injection of lidocaine, is then administered. The clinician is usually seated next to the patient. Then the
clinician marks exactly where the needle is to enter. As
the needle enters the joint, a ‘‘pop’’ may be felt or
heard. This is normal. Correct placement of the needle
in the joint space is normally painless. At this point,
the clinician slowly drains some of the fluid into the
syringe. The needle is then withdrawn and adhesive
tape is placed over the needle site.

Preparation
Glucose, or sugar, in the joint can be a signal of
arthritis. If the clinician will be doing a glucose test, the
patient will be asked to fast for 6-12 hours preceding
the procedure. If not, there is no special preparation
required for a joint fluid analysis.

Aftercare
Some post-procedural pain may be experienced.
For this reason, the patient should arrange to be driven home by someone else. Aftercare of the joints will
depend on the results of the analysis.

Risks
While joint fluid analysis is generally a safe procedure, especially when performed on a large, easily
accessible joint, such as the knee, some risks are
2095

Joint fluid analysis

Aftercare

Joint replacement

KEY TERMS
Aspirate—The removal by suction of a fluid from a
body cavity using a needle.
Bursae—A closed sac lined with a synovial membrane and filled with fluid, usually found in areas
subject to friction, such as where a tendon passes
over a bone.
Hematoma—A localized mass of blood that is confined within an organ or tissue.
Synovial fluid—A transparent lubricating fluid
secreted in a sac to protect an area where a tendon
passes over a bone.

possible. Some of the complications to the procedure,
although rare, include infection at the site of the needle
stick, an accumulation of blood (hematoma) formation, local pain, injury to cartilage, tendon rupture,
and nerve damage.

Normal results
The results of a normal joint fluid analysis include
fluid of a clear or pale-yellow color and the absence of
bacteria, fungus, and other cells, such as white blood
cells.

Abnormal results
The results of an abnormal joint fluid analysis
include fluid that is turbid, or cloudy. Also, white
blood cells and other blood cells may be found, from
which the clinician can make a diagnosis and arrive at
a treatment for the joint problem. An abnormal result
can indicate an infection caused by a bacteria, or
tuberculosis. Or, there might be inflammation that is
caused by gout, rheumatoid arthritis, or osteoarthritis.
Resources
BOOKS

Arnold, William J., and Robert W. Ike. ‘‘Specialized
Procedures in the Management of Patients with
Rheumatic Diseases.’’ In Cecil Textbook of Medicine,
edited by James B. Wyngaarden, et al. Philadelphia:
W. B. Saunders Co., 1996.

Ron Gasbarro, PharmD

Joint infection see Infectious arthritis
Joint radiography see Arthrography
2096

Joint replacement
Definition
Joint replacement is the surgical replacement of a
joint with an artificial prosthesis.

Purpose
Great advances have been made in joint replacement since the first hip replacement was performed in
the United States in 1969. Improvements have been
made in the endurance and compatibility of materials
used and the surgical techniques to install artificial
joints. Custom joints can be made using a mold of
the original joint that duplicate the original with a
very high degree of accuracy.
The most common joints to be replaced are hips
and knees. There is ongoing work on elbow and
shoulder replacement, but some joint problems are
still treated with joint resection (the surgical removal
of the joint in question) or interpositional reconstruction (the reassembly of the joint from constituent
parts).
Seventy percent of joint replacements are performed because arthritis has caused the joint to stiffen
and become painful to the point where normal daily
activities are no longer possible. If the joint does not
respond to conservative treatment such medication,
weight loss, activity restriction, and use of walking
aids such as a cane, joint replacement is considered
appropriate.
Patients with rheumatoid arthritis or other connective tissue diseases may also be candidates for
joint replacement, but the results are usually less satisfactory in those patients. Elderly people who fall and
break their hip often undergo hip replacement when
the probability of successful bone healing is low.
More than 170,000 hip replacements are performed in the United States each year. Since the lifetime of the artificial joint is limited, the best candidates
for joint replacement are over age 60.

Precautions
Joint replacements are performed successfully on
an older-than-average group of patients. People with
diseases that interfere with blood clotting are not good
candidates for joint replacement. Joint replacement
surgery should not be done on patients with infection,
or any heart, kidney or lung problems that would
make it risky to undergo general anesthesia.
GALE ENCYCLOPEDIA OF MEDICINE

Joint replacement

Description
Joint replacements are performed under general
or regional anesthesia in a hospital by an orthopedic
surgeon. Some medical centers specialize in joint
replacement, and these centers generally have a higher
success rate than less specialized facilities. The specific
techniques of joint replacement vary depending on the
joint involved.
Hip Replacement
The surgeon makes an incision along the top of
the thigh bone (femur) and pulls the thigh bone away
from the socket of the hip bone (the acetabulum). An
artificial socket made of metal coated with polyethylene (plastic) to reduce friction is inserted in the hip.
The top of the thigh bone is cut, and a piece of artificial
thigh made of metal is fitted into the lower thigh bone
on one end and the new socket on the other.
The artificial hip can either be held in place by a
synthetic cement or by natural bone in-growth. The
cement is an acrylic polymer. It assures good locking
of the prosthesis to the remaining bone. However,
bubbles left in the cement after it cures may act as
weak spots, causing the development of cracks. This
promotes loosening of the prosthesis later in life. If
additional surgery is needed, all the cement must be
removed before surgery can be performed.
An artificial hip fixed by natural bone in-growth
requires more precise surgical techniques to assure
maximum contact between the remaining natural
bone and the prosthesis. The prosthesis is made so
that it contains small pores that encourage the natural
bone to grow into it. Growth begins 6 to 12 weeks after
surgery. The short term outcome with non-cemented
hips is less satisfactory, with patients reporting more
thigh pain, but the long term outlook is better, with
fewer cases of hip loosening in non-cemented hips. The
trend is to use the non-cemented technique. Hospital
stays last from four to eight days.

The components of a prosthetic hip joint, removed due to
loosening. On the right is the metal shaft encased in the
cement which fixed it to the inside of the femur. On the left
is the plastic socket. (Custom Medical Stock Photo. Reproduced
by permission.)

and continued in pill form after the surgery. Fluid
and blood loss can be great, and sometimes blood
transfusions are needed.

Preparation
Knee Replacement
The doctor puts a tourniquet above the knee, then
makes a cut to expose the knee joint. The ligaments
surrounding the knee are loosened, then the shin bone
and thigh bone are cut and the knee removed. The
artificial knee is then cemented into place on the
remaining stubs of those bones. The excess cement is
removed, and the knee is closed. Hospital stays range
from three to six days.
In both types of surgery, preventing infection is
very important. Antibiotics are given intravenously
GALE ENCYCLOPEDIA OF MEDICINE

Many patients choose to donate their own blood
for transfusion during the surgery. This prevents any
blood incompatibility problems or the transmission of
bloodbourne diseases.
Prior to surgery, all the standard preoperative
blood and urine tests are performed, and the
patient meets with the anesthesiologist to discuss
any special conditions that affect the administration of anesthesia. Patients receiving general
anesthesia should not eat or drink for ten hours
prior to the operation.
2097

Joint replacement

out of bed to urinate. The patient will be monitored
for infection. Antibiotics are continued and pain
medication is prescribed. Physical therapy begins
(first passive exercises, then active ones) as soon as
possible using a walker, cane, or crutches for additional support. Long term care of the artificial joint
involves refraining from heavy activity and heavy
lifting, and learning how to sit, walk, how to get
out of beds, chairs, and cars so as not to dislocate
the joint.

Risks
The immediate risks during and after surgery
include the development of blood clots that may
come loose and block the arteries, excessive loss
of blood, and infection. Blood thinning medication
is usually given to reduce the risk of clots forming.
Some elderly people experience short term confusion and disorientation from the anesthesia.

A false color x-ray image of the human pelvis showing a
prosthetic hip joint. (Custom Medical Stock Photo. Reproduced
by permission.)

Although joint replacement surgery is highly
successful, there is an increased risk of nerve injury.
Dislocation or fracture of the hip joint is also a
possibility. Infection caused by the operation can
occur as long as a year later and can be difficult to
treat. Some doctors add antibiotics directly to the
cement used to fix the replacement joint in place.
Loosening of the joint is the most common cause of
failure in hip joints that are not infected. This may
require another joint replacement surgery in about
12% of patients within a 15-year period following
the first procedure.

Normal results

KEY TERMS
Catheterization—Inserting a tube into the bladder
so that a patient can urinate without leaving the
bed.
Prosthesis—A synthetic replacement for a missing
part of the body, such as a knee or a hip.
Rheumatoid arthritis—A joint disease of unknown
origins that may begin at an early age causing
deformity and loss of function in the joints.

More than 90% of patients receiving hip replacements achieve complete relief from pain and significant improvement in joint function. The success
rate is slightly lower in knee replacements, and
drops still more for other joint replacement
operations.
Resources
PERIODICALS

Siopack, Jorge, and Harry Jergensen. ‘‘Total Hip
Arthroplasty.’’ In Western Journal of Medicine March
1995: 43–50.

Tish Davidson, A.M.

Aftercare
Immediately after the operation the patient will
be catheterized so that he or she will not have to get
2098

Joint resection see Arthroplasty
Joint x rays see Arthrography
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Juvenile arthritis (JA), also called juvenile rheumatoid arthritis (JRA), refers to a number of different
conditions, all of which strike children, and all of
which have immune-mediated joint inflammation as
their major manifestation. JRA is also known as juvenile idiopathic arthritis or JIA. The European League
Against Rheumatism, or EULAR, refers to the disorder as juvenile chronic arthritis, or JCA.

Description
The skeletal system of the body is made up of
different types of the strong, fibrous tissue known
as connective tissue. Bone, cartilage, ligaments, and
tendons are all forms of connective tissue which
have different compositions, and thus different
characteristics.
The joints are structures which hold two or more
bones together. Some joints (synovial joints) allow for
movement between the bones being joined (called
articulating bones). The simplest model of a synovial
joint involves two bones, separated by a slight gap
called the joint cavity. The ends of each articular
bone are covered by a layer of cartilage. Both articular
bones and the joint cavity are surrounded by a tough
tissue called the articular capsule. The articular capsule has two components: the fibrous membrane on
the outside, and the synovial membrane (or synovium)
on the inside. The fibrous membrane may include
tough bands of fibrous tissue called ligaments, which
are responsible for providing support to the joints.
The synovial membrane has special cells and many
capillaries (tiny blood vessels). This membrane produces a supply of synovial fluid which fills the joint
cavity, lubricates it, and helps the articular bones
move smoothly about the joint.
In JA, the synovial membrane becomes intensely
inflamed. Usually thin and delicate, the synovium
becomes thick and stiff, with numerous infoldings on
its surface. The membrane becomes invaded by white
blood cells, which produce a variety of destructive
chemicals. The cartilage along the articular surfaces
of the bones may be attacked and destroyed, and the
bone, articular capsule, and ligaments may begin to be
worn away (eroded). These processes severely interfere
with movement in the joint.
JA specifically refers to chronic arthritic conditions which affect a child under the age of 16 years,
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
A number of different causes have been sought to
explain the onset of JA. There seems to be some
genetic link, based on the fact that the tendency to
develop JA sometimes runs in a particular family, and
based on the fact that certain genetic markers are more
frequently found in patients with JA and other related
diseases. Many researchers have looked for some
infectious cause for JA, but no clear connection to
a particular organism has ever been made. JA is considered by some to be an autoimmune disorder.
Autoimmune disorders occur when the body’s immune
system mistakenly identifies the body’s own tissue as
foreign, and goes about attacking those tissues, as if
trying to rid the body of an invader (such as a bacteria,
virus, or fungi). While an autoimmune mechanism is
strongly suspected, certain markers of such a mechanism (such as rheumatoid factor, often present in adults
with such disorders) are rarely present in children
with JA.
Joint symptoms of arthritis may include stiffness,
pain, redness and warmth of the joint, and swelling.
Bone in the area of an affected joint may grow too
quickly, or too slowly, resulting in limbs which are of
different lengths. When the child tries to avoid moving
a painful joint, the muscle may begin to shorten from
disuse. This is called a contracture.
Symptoms of JA depend on the particular subtype. According to criteria published by the American
College of Rheumatology (ACR) in 1973 and modified in 1977, JRA is classified by the symptoms that
appear within the first six months of the disorder:


Pauciarticular JA: This is the most common and the
least severe type of JA, affecting about 40–60% of all
JA patients. This type of JA affects fewer than four
joints, usually the knee, ankle, wrist, and/or elbow.
Other more general (systemic) symptoms are usually
absent, and the child’s growth usually remains normal. Very few children (less than 15%) with pauciarticular JA end up with deformed joints. Some
children with this form of JA experience painless
swelling of the joint. Some children with JA have a
serious inflammation of structures within the eye,
2099

Juvenile arthritis

Juvenile arthritis

and which last for a minimum of three to six months.
JA is often characterized by a waxing and waning
course, with flares separated by periods of time during
which no symptoms are noted (remission). Some literature refers to JA as juvenile rheumatoid arthritis,
although most types of JA differ significantly from the
adult disease called rheumatoid arthritis, in terms of
symptoms, progression, and prognosis.

Juvenile arthritis

which if left undiagnosed and untreated could even
lead to blindness. This condition is known as uveitis,
and affects about 20% of children diagnosed with
JRA.While many children have cycles of flares and
remissions, in some children the disease completely
and permanently resolves within a few years of
diagnosis.




Polyarticular JA: About 40% of all cases of JA are of
this type. More girls than boys are diagnosed with
this form of JA. This type of JA is most common in
children up to age three, or after the age of 10.
Polyarticular JA affects five or more joints simultaneously. This type of JA usually affects the small
joints of both hands and both feet, although other
large joints may be affected as well. Some patients
with arthritis in their knees will experience a different
rate of growth in each leg. Ultimately, one leg will
grow longer than the other. About half of all patients
with polyarticular JA have arthritis of the spine and/
or hip. Some patients with polyarticular JA will have
other symptoms of a systemic illness, including anemia (low red blood cell count), decreased growth
rate, low appetite, low-grade fever, and a slight
rash. The disease is most severe in those children
who are diagnosed in early adolescence. Some of
these children will test positive for a marker present
in other autoimmune disorders, called rheumatoid
factor (RF). RF is found in adults who have rheumatoid arthritis. Children who are positive for RF
tend to have a more severe course, with a disabling
form of arthritis which destroys and deforms the
joints. This type of arthritis is thought to be the
adult form of rheumatoid arthritis occurring at a
very early age.
Systemic onset JA: Sometimes called Still disease
(after a physician who originally described it), this
type of JA occurs in about 10–20% of all patients
with JA. Boys and girls are equally affected, and
diagnosis is usually made between the ages of 5–10
years. The initial symptoms are not usually related to
the joints. Instead, these children have high fevers; a
rash; decreased appetite and weight loss; severe joint
and muscle pain; swollen lymph nodes, spleen, and
liver; and serious anemia. Some children experience
other complications, including inflammation of the
sac containing the heart (pericarditis); inflammation
of the tissue lining the chest cavity and lungs (pleuritis); and inflammation of the heart muscle (myocarditis). The eye inflammation often seen in
pauciarticular JA is uncommon in systemic onset
JA. Symptoms of actual arthritis begin later in the
course of systemic onset JA, and they often involve
the wrists and ankles. Many of these children

2100

continue to have periodic flares of fever and systemic
symptoms throughout childhood. Some children will
go on to develop a polyarticular type of JA.


Spondyloarthropathy: This type of JA most commonly affects boys older than eight years of age.
The arthritis occurs in the knees and ankles, moving
over time to include the hips and lower spine.
Inflammation of the eye may occur occasionally,
but usually resolves without permanent damage.



Psoriatic JA: This type of arthritis usually shows up
in fewer than four joints, but goes on to include
multiple joints (appearing similar to polyarticular
JA). Hips, back, fingers, and toes are frequently
affected. A skin condition called psoriasis accompanies this type of arthritis. Children with this type of
JA often have pits or ridges in their fingernails. The
arthritis usually progresses to become a serious,
disabling problem.

As of 2003, there is some disagreement among
specialists about the classification of JRA. Some prefer the EULAR classification, also introduced in 1977,
to the ACR system. In 1997, the World Health
Organization (WHO) met in Durban and issued a
new classification system for JRA known as the
Durban criteria, in an attempt to standardize definitions of the various subtypes of JRA. None of the
various classification systems, however, are considered fully satisfactory as of early 2004.

Diagnosis
Diagnosis of JA is often made on the basis of the
child’s collection of symptoms. Laboratory tests often
show normal results. Some nonspecific indicators of
inflammation may be elevated, including white blood
cell count, erythrocyte sedimentation rate, and a marker called C-reactive protein. As with any chronic disease, anemia may be noted. Children with an
extraordinarily early onset of the adult type of rheumatoid arthritis will have a positive test for rheumatoid factor.

Treatment
Treating JA involves efforts to decrease the
amount of inflammation, in order to preserve movement. Medications which can be used for this include
nonsteroidal anti-inflammatory agents (such as ibuprofen and naproxen). Oral (by mouth) steroid medications are effective, but have many serious side effects
with long-term use. Injections of steroids into an
affected joint can be helpful. Steroid eye drops are
used to treat eye inflammation. Other drugs which
GALE ENCYCLOPEDIA OF MEDICINE

The Food and Drug Administration (FDA)
approved a new drug, etanercept, marketed under
the brand name Enbrel, in 1999. It is the most dramatic advancement in treating JRA in recent years. A
study by Children’s Hospital Medical Center in
Cincinnati, Ohio, released in 1999, showed the drug
was effective in 75% of children with severe JRA. The
drug eases joint pain, reduces swelling, and improves
mobility.
In 2003, a group of Japanese researchers noted
that the blood serum of patients with JRA contains
elevated levels of interleukin-6, a cytokine (nonantibody protein) that is critical to regulation of the
immune system and blood cell formation. Because
interleukin-6 is also associated with inflammation,
the researchers think that compounds inhibiting the
formation of interleukin-6 might provide new treatment options for JRA.

Alternative treatment
Alternative treatments that have been suggested
for arthritis include juice therapy, which can work to
detoxify the body, helping to reduce JA symptoms.
Some recommended fruits and vegetables to include
in the juice are carrots, celery, cabbage, potatoes,
cherries, lemons, beets, cucumbers, radishes, and garlic. Tomatoes and other vegetables in the nightshade
(potatoes, eggplant, red and green peppers) are discouraged. As an adjunct therapy, aromatherapy preparations utilize cypress, fennel, and lemon. Massage
oils include rosemary, benzoin, chamomile, camphor, juniper, and lavender. Other types of therapy
which have been used include acupuncture, acupressure, and body work. Nutritional supplements that
may be beneficial include large amounts of antioxidants (vitamins C, A, E, zinc, selenium, and flavenoids), as well as B vitamins and a full complement
of minerals (including boron, copper, manganese).
Other nutrients that assist in detoxifying the body,
including methionine, cysteine, and other amino
acids, may also be helpful. A number of autoimmune
disorders, including JA, seem to have a relationship
to food allergies. Identification and elimination of
reactive foods may result in a decrease in JA symptoms. Constitutional homeopathy can also work to
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Articular bones—Two or more bones which are
connected with each other via a joint.
Cytokine—A general term for nonantibody proteins released by a specific type of cell as part of
the body’s immune response.
Idiopathic—Of unknown cause or spontaneous
origin. JRA is sometimes called juvenile idiopathic
arthritis or JIA because its causes are still not fully
known.
Joint—A structure that holds two or more bones
together.
Rheumatology—The branch of medicine that specializes in the diagnosis and treatment of disorders
affecting the muscles and joints.
Synovial joint—A particular type of joint that
allows for movement in the articular bones.
Synovial membrane—The membrane that lines
the inside of the articular capsule of a joint
and produces a lubricating fluid called synovial
fluid.
Uveitis—Inflammation of the pigmented vascular
covering of the eye, which includes the choroid,
iris, and ciliary body. Uveitis is a common complication of JRA.

quiet the symptoms of JA and bring about balance to
the whole person.

Prognosis
The prognosis for pauciarticular JA is quite
good, as is the prognosis for spondyloarthropathy.
Polyarticular JA carries a slightly worse prognosis.
RF-positive polyarticular JA carries a difficult prognosis, often with progressive, destructive arthritis
and joint deformities. Systemic onset JA has a variable prognosis, depending on the organ systems
affected, and the progression to polyarticular JA.
About 1-5% of all JA patients die of such complications as infection, inflammation of the heart, or kidney disease.

Prevention
Because so little is known about what causes JA,
there are no recommendations available for how to
avoid developing it.
2101

Juvenile arthritis

have been used to treat JA include methotrexate, sulfasalazine, penicillamine, and hydroxychloroquine.
Physical therapy and exercises are often recommended
in order to improve joint mobility and to strengthen
supporting muscles. Occasionally, splints are used to
rest painful joints and to try to prevent or improve
deformities.

Juvenile arthritis

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Juvenile Rheumatoid Arthritis.’’ Section 19, Chapter
270 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Behrman, Richard, et al., editors. Nelson Textbook of Pediatrics.
16th ed. Philadelphia: W. B. Saunders Co., 2000.
Kredich, Deborah Welt. ‘‘Juvenile Rheumatoid Arthritis.’’
In Rudolph’s Pediatrics, edited by Abraham M.
Rudolph. Stamford:McGraw-Hill, 2002.
Peacock, Judith. Juvenile Arthritis. Mankato, MN:
LifeMatters Books, 2000.
PERIODICALS

de Boer, J., N. Wulffraat, and A. Rothova. ‘‘Visual Loss in
Uveitis of Childhood.’’ British Journal of
Ophthalmology 87 (July 2003): 879–884.
Henderson, Charles W. ‘‘Etancercept a Dramatic
Advancement in Treatment, Say Researchers.’’
Immunotherapy Weekly April 2, 2000.
Kotaniemi, K., A. Savolainen, A. Karma, and K. Aho.
‘‘Recent Advances in Uveitis of Juvenile Idiopathic
Arthritis.’’ Survey of Ophthalmology 48 (SeptemberOctober 2003): 489–502.
Larkin, Marilynn. ‘‘Juvenile Arthritis Helped by Resistance
Exercise.’’ Lancet November 20, 1999: 1797.
Manners, P., J. Lesslie, D. Speldewinde, and D. Tunbridge.
‘‘Classification of Juvenile Idiopathic Arthritis: Should

2102

Family History Be Included in the Criteria?’’ Journal of
Rheumatology 30 (August 2003): 1857–1863.
Moran, M. ‘‘Autoimmune Diseases Could Share Common
Genetic Etiology.’’ American Medical News 44, no. 38
(October 8, 2001): 38.
Yokota, S. ‘‘Interleukin 6 as a Therapeutic Target in
Systemic-Onset Juvenile Idiopathic Arthritis.’’ Current
Opinion in Rheumatology 15 (September 2003): 581–586.
ORGANIZATIONS

American College of Rheumatology. 1800 Century Place,
Suite 250, Atlanta, GA 30345. (404) 633-3777. <http://
www.rheumatology.org>.
Arthritis Foundation. 1330 West Peachtree St., Atlanta, GA
30309. (404) 872-7100. <http://www.arthritis.org>.
National Arthritis and Musculoskeletal and Skin Diseases
Information Clearinghouse. National Institutes of
Health, 1 AMS Circle, Bethesda, MD 20892. (301)
495-4484. <http://www.nih.gov/niams>.
OTHER

National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS). Questions and Answers About
Juvenile Rheumatoid Arthritis. NIH Publication No.
01-4942. Bethesda, MD: NIAMS, 2001. <http://
www.niams.nih.gov/hi/topics/juvenile_arthritis/
juvarthr.htm>.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

GALE ENCYCLOPEDIA OF MEDICINE

K

Kala-azar see Leishmaniasis

Kaposi’s sarcoma
Definition
Kaposi’s sarcoma is a form of skin cancer that can
involve internal organs. It most often is found in
patients with acquired immunodeficiency syndrome
(AIDS), and can be fatal.

Description
Kaposi’s sarcoma (KS) was once a very rare form
of cancer, primarily affecting elderly men of
Mediterranean and eastern European background,
until the 1980s, when it began to appear among
AIDS patients. It manifests in four distinct forms.
The first form, called classic KS, was described by
the Austrian dermatologist Moricz Kaposi more
than a century ago. Classic KS usually affects older
men of Mediterranean or eastern European backgrounds by producing tumors on the lower legs.
Though at times painful and disfiguring, they generally are not life-threatening. The second form of the
disease, African endemic KS, primarily affects boys
and men. It can appear as classic KS, or in a more
deadly form that quickly spreads to tissues below the
skin, the bones and lymph system, leading to death
within a few years of diagnosis. Another form of KS,
iatrogenic KS, is observed in kidney and liver transplant patients who take immunosuppressive drugs to
prevent rejection of their organ transplant. Iatrogenic
KS usually reverses after the immunosuppressive drug
is stopped. The fourth form of KS, AIDS-related KS,
emerged as one of the first illnesses observed among
those with AIDS. Unlike classic KS, AIDS-related KS
GALE ENCYCLOPEDIA OF MEDICINE

tumors generally appear on the upper body, including
the head, neck, and back. The tumors also can appear
on the soft palate and gum areas of the mouth. In more
advanced cases, they can be found in the stomach and
intestines, the lymph nodes, and the lungs.
Incidence of Kaposi’s sarcoma has been reported
as high as 20% in homosexual men who have HIV, 3%
in heterosexual intravenous drug users, 3% in women
and children, 3% in transfusion recipients, and 1%
in hemophiliacs. Once regarded as only a defining illness for AIDS, KS has proven to be a progressive,
fatal disease on its own, especially when the disease
becomes systemic. Yet involvement throughout the
body is not the only factor in patient mortality.
Research in 2000 found that patients with KS in oral
mucosa had a higher risk of death than those with KS
appearing only on the skin.

Causes and symptoms
A variety of factors appear to contribute to the
development of KS. One of the first avenues offered as
causal agents was genetic predisposition. People with
classic KS, and those who develop the tumors after
transplantation, are more likely than others to possess
a genetically determined immune factor called
HLA-DR. Cases of KS that run in families, however,
are rare.
The fact that the disease is more likely to afflict
men than women suggests sex hormones, such as testosterone in men, may stimulate the growth of KS
tumors, and that estrogen in women may retard their
growth.
Immune suppression was the next likely cause
since liver, kidney, and bone marrow patients who
take immunosuppressive drugs to prevent transplant
rejection frequently develop KS lesions. Similarly,
2103

Kaposi’s sarcoma

M O R I Z K A P O S I , (1837–1902)
Moriz Kohn Kaposi was born in 1837 to very poor
Hungarian parents. He studied dermatology under
Ferdinand von Hebra at the University of Vienna, earning
his medical degree in 1861. Kaposi took a position in
Hebra’s clinic and ultimately became a lecturer where he
was responsible for educating numerous dermatologists.
Kaposi and Hebra coauthored The Handbook of Diseases
of the Skin which had great success. Kaposi married
Hebra’s daughter and the couple had one son,
Hermann (1872). When Hebra died, Kaposi filled the
vacant spot as director of the skin clinic and as Vienna’s
most renowned dermatologist.
Between 1872 and 1887, Kaposi discovered nine
skin diseases that had not been previously documented.
His discovery of a malignant disease that strikes the
lymph nodes and skin (Kaposi’s sarcoma 1872) has
been documented as the most noteworthy. This disease
was seen relatively rarely in the United States until the
1980s when it was tied to AIDS. This sarcoma has been
the most common tumor found in AIDS patients. In 1872,
Kaposi also studied cases of lupus erythematosus, which
had no previous documentation. Kaposi was a prolific
writer who published Pathology and Treatment of
Diseases of the Skin in addition to numerous other publications, which he completed individually and with
other authors. Kaposi died in 1902.

KS has been observed in patients receiving systemic
treatment with high-dose corticosteroids, which also
suppresses the immune system. Immune suppression is
the hallmark of AIDS.
The current theory is the discovery of an infectious agent. A number of viruses have been proposed
as possible causes, including cytomegalovirus and
human papilloma virus, fragments of which have
been found in KS tumor specimens. A more likely
candidate, however, is a new herpes virus that has
been called human herpes virus 8 (HHV-8) or KSassociated herpes virus (KSHV). Since fragments of
the virus were first disclosed in KS samples in 1994,
they have since been found in KS samples taken from
patients with classic KS, African endemic KS, and KS
in transplant patients. Fragments of HHV-8, however,
also have been found in patients who have other skin
diseases but who do not have KS.
Studies in 2000 showed that HHV-8 was indeed
the culprit behind KS. Nevertheless, it does not work
alone. In combination with a patient’s altered
response to cytokines (regulatory proteins produced
2104

This HIV-positive patient is afflicted with Kaposi’s sarcoma
inside the mouth. (Custom Medical Stock Photo. Reproduced by
permission.)

by the immune system) and the HIV-1 transactivating
protein Tat which promotes the growth of endothelial
cells, HHV-8 can then encode interleukin 6 viral proteins. These specific cytokines stimulate cell growth in
the skin, becoming KS.
HHV-8 destroys the immune system further by
directing a cell to remove the major histocompatibility
complex (MHC-1) proteins that protect it from invasion. These proteins then are transferred to the interior
of the cell and are destroyed. This leaves the cell
unguarded and vulnerable to invaders which normally
would be targeted for attack by the immune system.
Research in early 2001 showed that transmission of
HHV-8 virus can be more casual than once was
thought, giving rise to incidence among women and
children. Women who are intravenous drug users and
who also have had a sexually transmitted disease have
been found to harbor HHV-8. This evidence shows that
women can contract HHV-8 through blood. In addition, researchers in 2000 found that HHV-8 could be
transmitted orally though kissing. This study found
more HHV-8 virus in oral samples than in genital secretions. In fact, HHV-8 was difficult to find in genital
samples. This may indicate why children and women
who were not intravenous drug users have had KS.
Kaposi’s sarcoma produces pink, purple, or
brown tumors on the skin, mucous membranes, or
internal organs.
GALE ENCYCLOPEDIA OF MEDICINE

Kaposi’s sarcoma

Diagnosis
Many physicians will diagnose KS based on the
appearance of the skin tumors and the patient’s medical history. Unexplained cough or chest pain, as well
as unexplained stomach or intestinal pain or bleeding,
could suggest that the disease has moved beyond the
skin. The most certain diagnosis can be achieved by
taking a biopsy sample of a suspected KS lesion and
examining it under high-power magnification. For
suspected involvement of internal organs, physicians
will use a bronchoscope to examine the lungs or an
endoscope to view the stomach and intestinal tract.

Treatment
Treatment goals for KS are simple: to reduce the
severity of symptoms, shrink tumors, and prevent disease progression. Unfortunately, there is no single best
treatment plan that can achieve all of these goals.
Treatments range from topical agents for mild disease
with few tumors to more aggressive systemic chemotherapy for more serious KS that has spread to
large areas of skin or the internal organs. Physicians
will frequently combine topical, radiation, and various
systemic chemotherapy drugs, depending on the sites
of the body affected, the speed at which it is progressing, and the patient’s overall health, among other
considerations.
Local therapy
When the number of KS tumors is small and the
disease appears to be progressing slowly, physicians
have had great success with the application, by the
patient, of a topical gel containing alitretinoin. This
product is a naturally occurring retinoid (a derivative
of vitamin A) that can inhibit cell growth and activate
apoptosis (cell death). Patients tolerate the product
well with only mild to moderate skin irritation at the
site of application in some individuals. Duration of
treatment is long term, with the patient seeing results
after four to eight weeks of therapy. Treatment slows
the progress of the disease and reduces the size of the
lesions.
Other local treatments include cryotherapy (using
a liquid nitrogen spray or probe to freeze the tumor),
injections of vinblastine (a drug also used for systemic
chemotherapy) directly into the tumor, laser therapy,
or radiation therapy targeted at the tumor sites. These
methods have some success, but they also have unpleasant side effects. Vinblastine injections are about
70% effective, but they do not resolve the lesions
completely.
GALE ENCYCLOPEDIA OF MEDICINE

Kaposi’s sarcoma usually appears on the lower extremities,
as evidenced on this patient’s hip. (Custom Medical Stock
Photo. Reproduced by permission.)

Systemic chemotherapy
With widespread KS lesions over the body surface,
or evidence of spread to other parts of the body, physicians will consider systemic chemotherapy drugs. A new
class of chemotherapy drugs, called liposomal anthracyclines, appears to produce good results with fewer
toxic side effects than do more conventional chemotherapy drugs. Two of these drugs, liposomal doxorubicin
(Doxil) and liposomal daunorubicin (DaunoXone) have
become the treatment of choice. These drugs last longer
in the human body, demonstrate higher concentrations
of the drug in tumors, and have fewer toxic side effects.
Paclitaxel (Taxol) is the newest drug in the KS
arsenal. It has a 75% effective rate and is very effective
in patients who are resistant to anthracycline drugs.
The 3-hour infusion time and the incidence of bone
marrow suppression, hair loss, and joint and muscle
pain make it less attractive to patients.
2105

Kaposi’s sarcoma

Antiretroviral therapy
Evidence suggests that for some individuals, the
class of AIDS drugs called protease inhibitors, in combination with other anti-HIV drugs, can reduce the
levels of detectable HIV in the blood to nearly zero,
and in some patients stabilize or reverse KS tumors.
A study late in 2003 showed that highly active antiretroviral therapy (HAART) containing a protease inhibitor helped block KS tumor growth, invasion and
distant spread. HAART is a treatment used to treat
HIV patients. Since the discovery of HHV-8, interest
in an antiviral approach to KS has increased. There is
no evidence, however, that two antiviral drugs commonly prescribed for herpes, acyclovir and ganciclovir, have any effect on the disease. One study of 20,000
patients with HIV and AIDS found that those who
took foscarnet, another antretroiviral medication that
works in a different way than acyclovir and ganciclovir, were less likely to develop KS tumors.
Another treatment source is interferon-alpha,
which is made by the body and has powerful effects
on the immune system. Investigators have tried injecting it directly into lesions, and also in combination
with other anti-HIV drugs such as zidovudine, with
some success. It has been used with patients who have
KS limited only to the skin and who have little immunosuppression. Interferon-alpha has had poor tumor
response and significant toxic effects in patients, especially those with seriously-depressed immune systems.
Still other avenues of therapy being researched are
sex hormones, thalidomide, SU5516 (an endothelial
growth factor inhibitor), and angiogenesis inhibitors,
which prevent the growth of blood vessels within a cell
that supplies oxygen and nutrients. There also is
some research involving the oral administration of
alitretinoin.

Alternative treatment
The Bastyr University AIDS Research Study has
been investigating and collecting data on treatment for
KS and other opportunistic conditions that are AIDSrelated. Among the treatments under investigation are
nutritional and herbal therapies (both internal and
external). Bastyr University is located in Seattle,
Washington.

Prognosis
The prognosis for patients with classic KS is good.
Tumors can frequently be controlled and patients frequently die of other causes before any serious spread.
African endemic KS can progress rapidly and lead to
2106

KEY TERMS
African endemic Kaposi’s sarcoma—Affects men
and boys; can appear like classic KS or in a more
lethal form.
AIDS-related Kaposi’s sarcoma—Emerged as one
of the first illnesses associated with AIDS patients.
These tumors usually appear on the upper body, the
soft palate and gum areas, and, as the disease
advances, in the lymph nodes, stomach, intestines,
and lungs.
Apoptosis—Cell death.
Classic Kaposi’s sarcoma—Usually affects older
men of Mediterranean or eastern European backgrounds, and produces tumors on the lower legs.
Cytokines—Regulatory proteins that are produced
by the immune system.
Human herpesvirus 8—Also called Kaposi’s
sarcoma-associated herpesvirus (KSHV). Thought
to be a viral cause for KS.
Iatrogenic Kaposi’s sarcoma—Develops in transplant patients who take immunosuppressive drugs
to prevent rejection of their organ transplant.
MCH-1—Major histocompatibility complex proteins that protect cells from invasion.

premature death, despite treatment. In AIDS-related
KS, milder cases can frequently be controlled; the
prognosis for more advanced and rapidly progressing
cases is less certain and dependent on the patient’s
overall medical condition. There are indications that
KS can be stabilized or reversed in patients whose level
of HIV in the blood is reduced to undetectable levels
via combined antiretroviral therapy.

Prevention
Safer sex practices may help to prevent AIDSrelated KS by decreasing the risk of transmission of
HHV-8 through sexual means. However, the addition
of avoidance of deep kissing to those precautions may
be necessary. Intravenous drug users should still be
urged not to share needles. Treatment with antiretrovirals may help to preserve the function of the immune
system in HIV patients and delay the appearance and
progression of KS lesions. In fact, since the introduction of HAART in those infected with HIV, KS has
decreased substantially. However, it still remains the
most common cancer among those infected with HIV.
GALE ENCYCLOPEDIA OF MEDICINE

Resources

black or white individuals, there does not appear to be
a distinctive geographic pattern of occurrence. Eighty
percent of cases involve children under the age of four.
Although the disease usually appears in individuals, it
sometimes affects several members of the same family
and occasionally occurs in small epidemics.

PERIODICALS

‘‘Alitretinoin Gel Effective for Treating Lesions.’’ AIDS
Weekly February 12, 2001.
Cannon, Michael J., A. Scott Laney, and Philip E. Pellett.
‘‘Human Herpesvirus 8: Current Issues.’’ Clinical
Infectious Diseases July 1, 2003: 82–86.
Dezube, Bruce J. ‘‘AIDS-Related Kaposi Sarcoma.’’
Archives of Dermatology 136, no. 2 (December 2000):
1554.
Henderson, Charles W. ‘‘Kissing May Spread Cause of
Kaposi’s Sarcoma.’’ Cancer Weekly November 21,
2000: NA.
Mann, Arnold. ‘‘Kaposi’s Lesions Benefit from Long-Term
Alitretinoin Gel Use.’’ Family Practice News 30, no. 19
(October 1, 2000): 12.
‘‘Protease Inhibitors Used for Treating HIV also Block
Kaposi Sarcoma.’’ Cancer Weekly 30, no. 19
(November 4, 2003): 125.
Rohrmus, Bettina, Eva M. Thoma-Greber, Hohannes R.
Bogner, and Martin Rocken. ‘‘Outlook in Oral and
Cutaneous Kaposi’s Sarcoma.’’ The Lancet 356,
no. 9248 (December 23, 2000): 2160.

Janie F. Franz
Teresa G. Odle

Kawasaki syndrome
Definition
Kawasaki syndrome is a potentially fatal inflammatory disease that affects several organ systems in
the body, including the heart, circulatory system,
mucous membranes, skin, and immune system. It
occurs primarily in infants and children but has also
been identified in adults as old as 34 years. Its cause is
unknown.

Description
Kawasaki syndrome, also called mucocutaneous
lymph node syndrome (MLNS), is an inflammatory
disorder with potentially fatal complications affecting
the heart and its larger arteries. Nearly twice as many
males are affected as females. Although persons of
Asian descent are affected more frequently than either
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The specific cause of Kawasaki syndrome is
unknown, although the disease resembles infectious
illnesses in many ways. It has been suggested that
Kawasaki syndrome represents an allergic reaction
or other unusual response to certain types of infections. Some researchers think that the syndrome may
be caused by the interaction of an immune cell, called
the T cell, with certain poisons (toxins) secreted by
bacteria.
Kawasaki syndrome has an abrupt onset, with
fever as high as 1048F (408C) and a rash that spreads
over the patient’s chest and genital area. The fever is
followed by a characteristic peeling of the skin beginning at the fingertips and toenails. In addition to the
body rash, the patient’s lips become very red, with
the tongue developing a ‘‘strawberry’’ appearance. The
palms, soles, and mucous membranes that line the
eyelids and cover the exposed portion of the eyeball
(conjuntivae) become purplish-red and swollen. The
lymph nodes in the patient’s neck may also become
swollen. These symptoms may last from two weeks to
three months, with relapses in some patients.
In addition to the major symptoms, about 30% of
patients develop joint pains or arthritis, usually in the
large joints of the body. Others develop pneumonia,
diarrhea, dry or cracked lips, jaundice, or an inflammation of the membranes covering the brain and
spinal cord (meningitis). A few patients develop symptoms of inflammation in the liver (hepatitis), gallbladder, lungs, or tonsils.
About 20% of patients with Kawasaki syndrome
develop complications of the cardiovascular system.
These complications include inflammation of the
heart tissue (myocarditis), disturbances in heartbeat
rhythm (arrhythmias), and areas of blood vessel dilation (aneurysms) in the coronary arteries. Other
patients may develop inflammation of an artery
(arteritis) in their arms or legs. Complications of the
heart or arteries begin to develop around the tenth
day after the illness begins, when the fever and rash
begin to subside. A few patients may develop gangrene, or the death of soft tissue, in their hands and
feet. The specific causes of these complications are
not yet known.
2107

Kawasaki syndrome

Large clinical trials underway in 2003 were
showing some promise for preventing infection with
HHV-8 through prophylaxis (preventive medication)
with antiherpes drugs.

Kawasaki syndrome

Since the cause of Kawasaki syndrome is
unknown, there are no laboratory tests that can confirm the diagnosis. The following test results, however,
are associated with the disease:

An angiogram showing abnormal coronary arteries in a child
suffering from Kawasaki’s disease. The coronary arteries are
abnormal and weakened in that they bulge into balloon
shapes, or aneurysms, along their lengths. This illness
afflicts children between the ages of 1–2 years. (Photograph
by Mehau Kulyk, Photo Researchers, Inc. Reproduced by
permission.)

Diagnosis
Because Kawasaki syndrome is primarily a disease of infants and young children, the disease is most
likely to be diagnosed by a pediatrician. The physician
will first consider the possible involvement of other
diseases that cause fever and skin rashes, including
scarlet fever, measles, Rocky Mountain spotted fever,
toxoplasmosis (a disease carried by cats), juvenile rheumatoid arthritis, and a blistering and inflammation of
the skin caused by reactions to certain medications
(Stevens-Johnson syndrome).
Once other diseases have been ruled out, the
patient’s symptoms will be compared with a set of
diagnostic criteria. The patient must have a fever lasting five days or longer that does not respond to antibiotics, together with four of the following five
symptoms:



Blood tests show a high white blood cell count, high
platelet count, a high level of protein in the blood
serum, and mild anemia



Chest x ray may show enlargement of the heart
(cardiomegaly)



Urine may show the presence of pus or an abnormally high level of protein



An electrocardiogram may show changes in the
heartbeat rhythm

In addition to these tests, it is important to take a
series of echocardiograms during the course of the
illness because 20% of Kawasaki patients will develop
coronary aneurysms or arteritis that will not appear
during the first examination.

Treatment
Kawasaki syndrome is usually treated with a
combination of aspirin, to control the patient’s fever
and skin inflammation, and high doses of intravenous immune globulin to reduce the possibility of
coronary artery complications. Some patients with
heart complications may be treated with drugs that
reduce blood clotting or may receive corrective
surgery.
Follow-up care includes two to three months of
monitoring with chest x rays, electrocardiography, and
echocardiography. Treatment with aspirin is often continued for several months.

Prognosis
Most patients with Kawasaki syndrome will
recover completely, but about 1–2% will die as a
result of blood clots forming in the coronary arteries
or as a result of a heart attack. Deaths are sudden
and unpredictable. Almost 95% of fatalities occur
within six months of infection, but some have been
reported as long as 10 years afterward. Long-term
follow-up of patients with aneurysms indicates that
about half show some healing of the aneurysm. The
remaining half has a high risk of heart complications
in later life.



Inflammation of the conjunctivae of both eyes with
no discharge



At least one of the following changes in the mucous
membranes of the mouth and throat: ‘‘strawberry’’
tongue; cracked lips; or swollen throat tissues



At least one of the following changes in the hands or
feet: swelling caused by excess fluid in the tissues;
peeling of the skin; or abnormal redness of the skin



A skin eruption or rash associated with fever
(exanthem) on the patient’s trunk

Resources



Swelling of the lymph nodes in the neck to a size
greater than 1.5 cm.

Shandera, Wayne X., and Maria E. Carlini. ‘‘Infectious
Diseases: Viral & Rickettsial.’’ In Current Medical

2108

BOOKS

GALE ENCYCLOPEDIA OF MEDICINE

Aneurysm—Dilation of an artery caused by thinning and weakening of the vessel wall.
Arrythmia—Abnormal heart rhythm.
Arteritis—Inflammation of an artery.
Cardiomegaly—An enlarged heart.
Conjunctivae—The mucous membranes that cover
the exposed area of the eyeball and line the inner
surface of the eyelids.
Exanthem—A skin eruption associated with a disease, usually one accompanied by fever as in
Kawasaki syndrome.
Gangrene—The death of soft tissue in a part of the
body, usually caused by obstructed circulation.
Hepatitis—Inflammation of the liver.
Meningitis—Inflammation of the membranes,
called the meninges, covering the brain and spinal
cord.
Mucocutaneous lymph node syndrome (MLNS)—
Mucocutaneous lymph node syndrome, another
name for Kawasaki syndrome. The name comes
from the key symptoms of the disease, which
involve the mucous membranes of the mouth and
throat, the skin, and the lymph nodes.
Myocarditis—Inflammation of the heart muscle.
Stevens-Johnson syndrome—A severe inflammatory skin eruption that occurs as a result of an
allergic reaction or respiratory infection.
T cell—A type of white blood cell that develops in
the thymus gland and helps to regulate the immune
system’s response to infections or malignancy.

Diagnosis and Treatment, 1998, edited by Stephen
McPhee, et al., 37th ed. Stamford: Appleton &
Lange, 1997.

Rebecca J. Frey, PhD

Keloids
Definition
Keloids are overgrowths of fibrous tissue or scars
that can occur after an injury to the skin. These heavy
GALE ENCYCLOPEDIA OF MEDICINE

scars are also called cheloid or hypertrophic scars. In
individuals prone to keloids, even minor traumas to
the skin, such as ear piercing, can cause keloids. The
word ‘‘keloid’’ itself comes from the Greek word for a
crab’s claw; it was first used by a French physician to
describe the way that keloids grow sideways into normal skin.

Description
Keloids can occur anywhere on the body, but they
are most common on the earlobes, upper back, shoulders,
and chest. The pattern of distribution of keloids differs
according to race, with facial keloids more common in
Caucasians and relatively uncommon in Asians. African
Americans are more likely to develop keloids on the legs
or feet than either Asians or Caucasians. In general,
keloids consist of hard, raised scars that may be slightly
pink or whitish. These may itch and be painful, and some
keloids can grow to be quite large.

Causes and symptoms
Although the cause of keloids is unknown, it is
thought that they are due to the body’s failure to turn
off the healing process needed to repair skin. When
this occurs, extra collagen forms at the site of the scar,
and keeps forming because it is not shut off. This
results in keloid formation.
Keloids occur most frequently in individuals of
African-American descent and in those with darker
skin. They are more common in Polynesians and
Chinese than in people from India or Malaysia.
Caucasians are the least frequently affected by keloids.
Other risk factors include a family history of keloids,
surgery, acne, burns, ear piercing, vaccinations, or even
insect bites. Spontaneous keloids have been reported
occasionally in siblings. In addition, women and young
people under the age of 30 are more prone to develop
them. Keloids are infrequent among the elderly.
Although the association of keloids with darker
skin pigmentation suggests a genetic linkage of some
sort, no specific genes have been identified in connection with keloids as of the early 2000s.
Initially, keloids will begin as a small lump where
the skin has been injured. This lump grows and can
eventually become very large and cosmetically
unacceptable.

Diagnosis
A dermatologist can usually make the diagnosis of
a keloid based on looking at the scar. In some cases,
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Keloids

KEY TERMS

Keloids

however, a biopsy may be necessary to rule out other
types of skin lesions, such as tumors.

Treatment
The treatment of choice for keloids is usually an
injection of corticosteroid drugs such as cortisone
directly into the lesion. These injections cause the
keloid to become atrophic, or thinner, and are
repeated every three to four weeks until the keloid
has been resolved to the individual’s satisfaction.
Other therapies include laser treatment or radiation
therapy, and topical treatments are undergoing study.
Surgery is often used in combination with corticosteroid injections. The injections are given for several weeks, and then the keloid is surgically removed.
The injections are then continued for several weeks.
Surgical removal of the keloid may also be used in
conjunction with radiation therapy, which delivers
small amounts of radiation to the affected area.
Another surgical option is cryosurgery, in which
liquid nitrogen is used to freeze the tissues in the
keloid. The treatment may need to be repeated to
remove as much of the keloid as possible; however,
cryosurgery prevents keloids from recurring in about
70% of patients.

KEY TERMS
Atrophy—A wasting away of, becoming thinner,
less strong.
Corticosteroids—Any of several steroid medications used to suppress inflammation, allergic, or
immune responses of the body.
Cryosurgery—The use of extreme cold to kill or
remove tissue.

Prevention
Preventive measures include avoiding any trauma
to the skin, and compression pressure dressing for
high-risk patients who have suffered burns to their
skin. Patients with a tendency to form keloids should
avoid any sort of elective surgery. Individuals who are
prone to develop keloids or who have a history of
keloids should immediately care for any cuts or abrasions they may sustain.
To lower the risk of keloids, surgeons are advised
to close incisions with as little tension on the sutures as
possible, and to use buried sutures whenever possible.

Newer approaches include silastic gel sheeting,
which makes use of pressure to flatten the keloid.
The gel is applied and kept securely in place with
tape, cloth, or an Ace bandage. The dressing is to
be changed every seven to 10 days for as long as
12 months.

Resources

Finally, researchers are now studying a type of
tape that has been soaked with steroids, which
are released slowly into the keloid, causing it to thin
over time.

PERIODICALS

Newer treatments include injections of interferon
directly into the keloids, and local application of 5%
imiquimod cream, which induces the skin where it is
applied to produce interferon. The imiquimod cream
is reported to significantly lower the risk of keloid
recurrence.

Prognosis
Although keloids are unsightly, they are not lifethreatening. Keloids do not have a tendency to
develop into malignancies, but they can become cosmetically unacceptable. Keloids can gradually lessen
after treatment, but many recur. And just as they can
occur spontaneously, they can also resolve
spontaneously.
2110

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Benign Tumors.’’ Section 10, Chapter 125 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Berman, Brian, MD, PhD, and Sonia Kapoor, MBBS.
‘‘Keloid and Hypertrophic Scar.’’ eMedicine November
30, 2001. <http://www.emedicine.com/derm/
topic205.htm>.
Dinh, Q., M. Veness, and S. Richards. ‘‘Role of Adjuvant
Radiotherapy in Recurrent Earlobe Keloids.’’
Australasian Journal of Dermatology 45 (August 2004):
162–166.
Food and Drug Administration (FDA). ‘‘General and
Plastic Surgery Devices; Classification of Silicone
Sheeting. Final Rule.’’ Federal Register 69 (August 9,
2004): 48146–48148.
Mandal, A., D. Imran, and G. S. Rao. ‘‘Spontaneous
Keloids in Siblings.’’ Irish Medical Journal
97 (September 2004): 250–251.
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, PO Box 4014, Schaumburg, IL 60168-4014. (847)
330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
GALE ENCYCLOPEDIA OF MEDICINE



loss of vision



glaucoma

OTHER

This infection generally begins with inflammation
of the membrane lining the eyelid (conjunctiva) and
the portion of the eyeball that comes into contact with
it. It usually occurs in one eye. Subsequent infections
are characterized by a pattern of lesions that resemble
the veins of a leaf. These infections are called dendritic
keratitis and aid in the diagnosis.

<http://www.skinsite.com>.
‘‘Keloids.’’ Black Women’s Health. <http://www.blackwomenshealth.com/Keloids.htm>.

Liz Meszaros
Rebecca J. Frey, PhD

Recurrences may be brought on by stress, fatigue,
or ultraviolet light (UV) exposure (e.g., skiing or boating increase the exposure of the eye to sunlight; the
sunlight reflects off of the surfaces). Repeated episodes
of dendritic keratitis can cause sores, permanent scarring, and numbness of the cornea.

Keratitis
Definition
Keratitis is an inflammation of the cornea, the
transparent membrane that covers the colored part
of the eye (iris) and pupil of the eye.

Description
There are many types and causes of keratitis.
Keratitis occurs in both children and adults.
Organisms cannot generally invade an intact, healthy
cornea. However, certain conditions can allow an
infection to occur. For example, a scratch can leave
the cornea open to infection. A very dry eye can also
decrease the cornea’s protective mechanisms.
Risk factors that increase the likelihood of developing this condition include:


poor contact lens care; overuse of contact lenses



illnesses or other factors that reduce the body’s
ability to overcome infection



cold sores,
infections



crowded, dirty living conditions; poor hygiene



poor nutrition (especially a deficiency of Vitamin A,
which is essential for normal vision)

genital

herpes,

and

other

viral

Some common types of keratitis are listed below,
however there are many other forms
Herpes simplex keratitis
A major cause of adult eye disease, herpes simplex
keratitis may lead to:

Recurrent dendritic keratitis is often followed by
disciform keratitis. This condition is characterized by
clouding and deep, disc-shaped swelling of the cornea
and by inflammation of the iris.
It is very important not to use topical corticosteroids with herpes simplex keratitis as it can make it
much worse, possibly leading to blindness.
Bacterial keratitis
People who have bacterial keratitis wake up with
their eyelids stuck together. There can be pain, sensitivity to light, redness, tearing, and a decrease in
vision. This condition, which is usually aggressive,
can be caused by wearing soft contact lenses overnight. One study found that overnight wear can
increase risk by 10-15 times more than if wearing
daily wear contact lenses. Improper lens care is also a
factor. Contaminated makeup can also contain
bacteria.
Bacterial keratitis makes the cornea cloudy.
It may also cause abscesses to develop in the
stroma, which is located beneath the outer layer of
the cornea.
Fungal keratitis
Usually a consequence of injuring the cornea in a
farm-like setting or in a place where plant material is
present, fungal keratitis often develops slowly. This
condition:


usually affects people with weakened immune
systems



chronic inflammation of the cornea



development of tiny blood vessels in the eye



often results in infection within the eyeball



scarring



may cause stromal abscesses

GALE ENCYCLOPEDIA OF MEDICINE

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Keratitis

United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA.<http://www.fda.gov>.

Keratitis

very painful and may occur several hours after exposure. It may last one to two days.
Interstitial keratitis
Also called parenchymatous keratitis, interstitial
keratitis is a chronic inflammation of tissue deep
within the cornea. Interstitial keratitis is rare in the
United States. Interstitial keratitis affects both eyes
and usually occurs as a complication of congenital or
acquired syphilis. In congenital syphilis it can occur
between age two and puberty. It may also occur in
people with tuberculosis, leprosy, or other diseases.
Close-up of a damaged cornea due to complications following cataract surgery. (Custom Medical Stock Photo. Reproduced
by permission.)

Peripheral ulcerative keratitis
Peripheral ulcerative keratitis is also called marginal keratolysis or peripheral rheumatoid ulceration.
This condition is often associated with active or
chronic:

Causes and symptoms
In summary, keratitis can be caused by:


bacterial, viral, or fungal infections



dry eyes resulting from disorders of the eyelid or
diminished ability to form tears



exposure to very bright light



foreign objects that injure or become lodged in the
eye



rheumatoid arthritis



relapsing
polychondritis
inflammation)

(connective-tissue



sensitivity or allergic reactions to eye makeup, dust,
pollen, pollution, or other irritants



Wegener’s granulomatosis, a rare condition characterized by kidney disease and development of nodules
in the respiratory tract



vitamin A deficiency, which people with normal diets
rarely develop
Symptoms of keratitis include, but are not limited

to:
Superficial punctate keratitis
Often associated with the type of viruses that
cause upper respiratory infection (adenoviruses),
superficial punctate keratitis is characterized by
destruction of pinpoint areas in the outer layer of the
cornea (epithelium). One or both eyes may be affected.
Acanthamoeba keratitis
This pus-producing condition is very painful. It is
a common source of infection in people who wear soft
or rigid contact lenses. It can be found in tap water,
soil, and swimming pools.
Photokeratitis
Photokeratitis or snowblindness is caused by
excess exposure to UV light. This can occur with sunlight, suntanning lamps, or a welding arc. It is called
snowblindness because the sunlight is reflected off of
the snow. It therefore can occur in water sports as well,
because of the reflection of light off of the water. It is
2112



tearing



pain



sensitivity to light



inflammation of the eyelid



decrease in vision



redness

Diagnosis
A case history will be taken and the vision will be
tested. Examination with a slit lamp, an instrument
that’s a microscope and focuses a beam of light on the
eye is important for diagnosis. The cornea can be
examined with fluorescein, a yellow dye which will
highlight defects in the cornea. Deeper layers of the
cornea can also be examined with the slit lamp.
Infiltrates, hazy looking areas in the cornea, can be
seen by the doctor and will aid in the diagnosis.
Samples of infectious matter removed from the eye
will be sent for laboratory analysis.
GALE ENCYCLOPEDIA OF MEDICINE

Abscess—A collection of pus.
Glaucoma—An eye disease characterized by an
increase of pressure in the eye. Left untreated,
blindness may result.
Infiltrate—A collection of cells not usually present
in that area. In the cornea, infiltrates may be a
collection of white blood cells.
Inflammation—A localized response to an injury.
May include swelling, redness, and pain.

Treatment
Antibiotics, antifungals, and antiviral medication
will be used to treat the appropriate organism. Broad
spectrum antibiotics will be used immediately, but
once the lab analysis determines the offending organism, the medication may be changed. Sometimes more
than one medication is necessary. It depends upon the
infection, but the patient should be clear on how often
and how to use the medications.
A sterile, cotton-tipped applicator may be used to
gently remove infected tissue and allow the eye to heal
more rapidly. Laser surgery is sometimes performed to
destroy unhealthy cells, and some severe infections
require corneal transplants.
Antifungal, antibiotic, or antiviral eyedrops or
ointments are usually prescribed to cure keratitis, but
they should be used only by patients under a doctor’s
care. Inappropriate prescriptions or over-the-counter
preparations can make symptoms more severe and
cause tissue deterioration. Topical corticosteroids
can cause great harm to the cornea in patient’s with
herpes simplex keratitis.

Children and adults who wear contact lenses
should always use sterile lens-cleaning and disinfecting solutions. Tap water is not sterile and should not
be used to clean contact lenses. It is important to go
for follow-up checkups because small defects in the
cornea can occur without the patient being aware of
it. Do not overwear contact lenses. Remove them if
the eyes become red or irritated. Replace contact
lenses when scheduled to do so. Proteins and other
things can deposit on the contacts, leading to an
increased risk of infection. Rinse contact lens cases
in hot water every night, if possible, and let them air
dry. Replace contact lens cases every three months.
Organisms have been cultured from contact lens
cases.
Eating a well-balanced diet and wearing protective glasses when working or playing in potentially
dangerous situations can reduce anyone’s risk of
developing keratitis. Protective goggles can even be
worn mowing the lawn so that if twigs are tossed
up they can’t hurt the eye. Goggles or sunglasses
with UV coatings can help protect against damage
from UV light.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
National Eye Institute. 2020 Vision Place, Bethesda, MD
20892-3655. (301) 496-5248. <http:// www.nei.nih.gov>.
Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://
www.preventblindness.org>.

A patient with keratitis may wear a patch to protect the healing eye from bright light, foreign objects,
the lid rubbing against the cornea, and other irritants.
Sometimes a patch can make it worse, so again, the
patient must discuss with the doctor whether or not a
patch is necessary. The patient will probably return
every day to the eye doctor to check on the progress.
Although early detection and treatment can cure
most forms of keratitis, the infection can cause:


glaucoma



permanent scarring



ulceration of the cornea



blindness

GALE ENCYCLOPEDIA OF MEDICINE

Maureen Haggerty

Keratosis pilaris
Definition
Keratosis pilaris is a common skin condition
that looks like small goose bumps, which are actually dead skin cells that build up around the hair
follicle.
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Keratosis pilaris

Prevention

KEY TERMS

Kidney biopsy

Description
Keratosis pilaris is a disorder that occurs around
the hair follicles of the upper arms, thighs, and sometimes the buttocks. It presents as small, benign bumps
or papules that are actually waxy build-ups of keratin.
Normally skin sloughs off. However, around the hair
follicle where the papules form, the keratinized skin
cells slough off at a slower rate, clogging the follicles.
This is generally thought to be genetic disorder,
although the symptoms of keratosis pilaris are often
seen with ichthyosis and allergic dermatitis. It can also
be observed in people of all ages who have either
inherited it or have a vitamin A deficiency or have dry
skin. Keratosis pilaris is a self-limiting disorder that
disappears as the person ages. It can become more
severe when conditions are dry such as during the
winter months or in dry climates.

KEY TERMS
Benign—Not cancerous.
Dermatologist—A physician that specializes in diseases and disorders of the skin.
Ichthyosis—A group of congenital disorders of keratinization characterized by dryness and scaling of
the skin.
Keratin—The hard, waxy material that is made by
the outer layer of skin cells.

the dermatologist and applied one to two times daily.
Systemic (oral) medications are not prescribed for
keratosis pilaris. However if papules are opened and
become infected, antibiotics may be necessary to treat
the infection.

Causes and symptoms
The specific causes of this disorder are unknown.
Since this disorder runs in families, it is thought to be
hereditary. Keratosis pilaris is not a serious disorder
and is not contagious.
The symptoms of keratosis pilaris are based on the
development of small white papules the size of a grain
of sand on the upper arms, thighs, and occasionally
the buttocks and face. The papules occur around a
hair follicle and are firm and white. They feel a little
like coarse sandpaper, but they are not painful and
there usually is no itching associated with them. They
are easily removed and the material inside the papule
usually contains a small, coiled hair.

Diagnosis

Prognosis
Unfortunately, the treatment for keratosis pilaris
is often disappointing. Although extreme cases of keratosis pilaris can occasionally be unsightly, the disorder is not life threatening and usually begins to
disappear as the patient ages.

Prevention
Since keratosis pilaris is thought to be a genetic
disorder and is observed in several members of the
same family, there is nothing that can be done to
prevent this disorder. Following the treatment advice
above can alleviate the outward characteristics of keratosis pilaris.

A dermatologist or a general practicioner can
easily diagnose this disorder. A physical examination
is all that is necessary to diagnose keratosis pilaris.
Special tests are not needed.

Treatment
To treat keratosis pilaris patients can try several
strategies to lessen the bumps. First, the patient can
supplement the natural removal of dry skin and
papules by using a loofah or another type of scrub
showering or bathing. A variety of different overthe-counter (OTC) lotions, ointments, and creams
can also be applied after showering while the skin is
still moist and then several times a day to keep the area
moist. Medicated lotions with urea, 15% alphahydroxy acids, or Retin A can also be prescribed by
2114

Sally C. McFarlane-Parrott

Kidney biopsy
Definition
Kidney biopsy is a medical procedure in which a
small piece of tissue is removed from the kidney for
microscopic examination.

Purpose
The test is usually done to diagnose kidney disease
and to evaluate the extent of damage to the kidney.
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
The biopsy is not recommended for patients who
have any uncontrollable bleeding disorders. Platelets
are blood cells that play an important role in the blood
clotting process. If the bleeding disorder is caused by a
low platelet count (less than 50,000 per cubic
millimeter of blood), then a platelet transfusion can
be done just before performing the biopsy.

Description

breathe normally. The tissue is collected for examination and the needle is withdrawn. The needle may be
re-inserted into another part of the kidney so that
tissue is collected from at least three different areas.
The tissue samples are sent to the laboratory for examination. The entire procedure may last about an hour.

Preparation
Before performing the biopsy, the doctor should
be made aware of all the medications that the patient is
taking. The doctor should also be told whether the
patient is allergic to any medications. The procedure
and the risks of the procedure are explained to the
patient and the necessary consent forms are obtained.
The patient should be told that a kidney biopsy
requires a 24-hour stay in the hospital after the biopsy.
Some doctors order blood tests to check for clotting problems before performing the biopsy. The
patient’s blood type may also be determined in case a
transfusion becomes necessary.

The kidneys, a pair of organs that are shaped like
beans, lie on either side of the backbone, just above the
waist. The periphery (parenchyma) of the kidney is
made up of tiny tubes. These tubes filter and clean
the blood by taking out the waste products and making urine. The urine is collected in the central portion
of the kidney. Tubes called ureters drain the urine
from the kidney into the bladder, where it is held
until it is voided from the body.

Immediately after the biopsy, pulse, respiration,
and temperature (vital signs) are measured. If they are
stable, the patient is instructed to lie flat in bed for
at least 12 hours. The pulse and blood pressure are
checked at regular intervals by the nursing staff. All
urine voided by the patient in the first 12–24 hours is
examined in the laboratory for blood cells.

A kidney specialist (nephrologist) performs the
biopsy. It can be done either in the doctor’s office or
in a local hospital. The patient may be given a calming
drug before the procedure to help him relax. The skin
and muscles on the back overlying the site that is to be
biopsied may be numbed with local anesthesia.

If bleeding is severe, iron levels in the blood drop
significantly, or the patient complains of severe pain at
the biopsy site, the physician should be contacted
immediately. After the patient goes home, he should
avoid heavy lifting, vigorous exercise, and contact
sports for at least one or two weeks.

The patient will be asked to lie face down and a
pad or a rolled towel may be placed under the stomach. Either the left or the right kidney may be biopsied depending on the results of the imaging tests:
x rays, computed tomography scans (CT scans), magnetic resonance imaging (MRI), and ultrasound. The
area that will be biopsied is cleaned with an antiseptic
solution and sterile drapes are placed on it. The skin is
numbed with local anesthesia. A small incision is made
on the skin with a scalpel blade. Using a long needle,
the physician injects local anesthesia into the incision
so that it infiltrates down to the kidney. The biopsy
needle is then advanced slowly through the incision.
The patient is asked to hold his or her breath each time
the needle is pushed forward. Once the wall (capsule)
of the kidney has been penetrated, the patient can
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare

Risks
The risks of a kidney biopsy are very small. Severe
bleeding may occur after the procedure. There is also a
slight chance that an infection or a lump of blood
under the skin that looks black and blue (hematoma)
may develop. In most cases, the hematoma disappears
by itself and does not cause any pain. However, severe
pain or a drop in blood pressure and iron levels in the
blood indicates that the hematoma is expanding. This
condition could lead to complications and should be
reported immediately to the doctor.
Very rarely, the patient may develop high blood
pressure (hypertension), and the bleeding may be
severe enough to require a transfusion. In extremely
2115

Kidney biopsy

A biopsy is also frequently ordered to detect the reason for acute renal failure when normal office procedures and tests fail to establish the cause. In addition,
information regarding the progression of the disease
and how it is responding to medical treatment can be
obtained from a biopsy. Occasionally a biopsy may be
done to confirm a diagnosis of kidney cancer, to determine its aggressiveness, and decide on the mode of
treatment.

Kidney cancer

KEY TERMS
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Computed tomography (CT) scan—A medical procedure in which a series of x rays are taken and put
together by a computer in order to form detailed
pictures of areas inside the body.
Magnetic resonance imaging (MRI)—A medical
procedure used for diagnostic purposes in which
pictures of areas inside the body can be created
using a magnet linked to a computer.
Nephrologist—A doctor who specializes in the diseases and disorders of the kidneys.
Renal ultrasound—A painless and non-invasive
procedure in which sound waves are bounced off
the kidneys. These sound waves produce a pattern
of echoes that are then used by the computer
to create pictures of areas inside the kidney
(sonograms).

rare circumstances, the kidney may rupture, or the
surrounding organs (pancreas, bowel, spleen, and
liver) may be punctured. Death occurs in about one
in 3000 cases.

Normal results
The results are normal if no abnormalities can be
seen in the tissue samples with the naked eye, with an
electron microscope or through staining with a fluorescent dye (immunofluorescence).

Abnormal results
Any abnormalities in the size, color, and consistency of the sample will be reported as an abnormal
result. In addition, any change in the structure of the
renal tubules, the presence of red blood cells, or
abnormalities in the cells are considered an abnormal
result. If cancerous changes are detected in the kidney
cells, they are further characterized in order to determine the stage of the tumor and decide on the appropriate mode of treatment.

National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010.<http://www.kidney.org>.

Lata Cherath, PhD

Kidney cancer
Definition
Kidney cancer is a disease in which the cells in
certain tissues of the kidney start to grow uncontrollably and form tumors. Renal cell carcinoma, which
occurs in the cells lining the kidneys (epithelial cells), is
the most common type of kidney cancer. Eighty-five
percent of all kidney tumors are renal cell carcinomas.
Wilms’ tumor is a rapidly developing cancer of the
kidney most often found in children under four years
of age.

Description
The kidneys are a pair of organs shaped like kidney beans that lie on either side of the spine just above
the waist. Inside each kidney are tiny tubes (tubules)
that filter and clean the blood, taking out the waste
products and making urine. The urine that is made by
the kidney passes through a tube called the ureter into
the bladder. Urine is held in the bladder until it is
discharged from the body. Renal cell carcinoma generally develops in the lining of the tubules that filter
and clean the blood. Cancer that develops in the central portion of the kidney (where the urine is collected
and drained into the ureters) is known as transitional
cell cancer of the renal pelvis. Transitional cell cancer
is similar to bladder cancer.
Kidney cancer accounts for approximately 2–3%
of all cancers. In the United States, kidney cancer is
the tenth most common cancer and the incidence has
increased by 43% since 1973; the death rate has
increased by 16%. According to the American
Cancer Society, 35,710 Americans were diagnosed
with kidney cancer in 2004, and 12,480 died from the
disease. RCC accounts for 90–95% of malignant neoplasms that originate from the kidney.

Causes and symptoms
Resources
ORGANIZATIONS

National Kidney Cancer Association. 1234 Sherman Ave.,
Suite 203, Evanston, IL 60202-1375. (800) 850-9132.

2116

The causes of kidney cancer are unknown, but
men seem to have a greater risk than women of contracting the disease; the male:female ratio in the
United States and Canada is 3:2 as of the early
GALE ENCYCLOPEDIA OF MEDICINE

The most common symptom of kidney cancer is
blood in the urine (hematuria). Other symptoms
include painful urination, pain in the lower back or
on the sides, abdominal pain, a lump or hard mass that
can be felt in the kidney area, unexplained weight loss,
fever, weakness, fatigue, and high blood pressure.
Other symptoms may occur if the cancer has
spread beyond its original location. Spread of kidney
cancer most commonly occurs to the lung (55%), liver
(33%), bone (33%), adrenal (20%), and opposite kidney (10%). Lymph node spread is also common,
occurring in about 25% of patients).

Diagnosis
A diagnostic examination for kidney cancer
includes taking a thorough medical history and making a complete physical examination in which the doctor will probe (palpate) the abdomen for lumps. Blood
tests will be ordered to check for changes in blood
chemistry caused by substances released by the
tumor. Laboratory tests may show abnormal levels
of iron in the blood. Either a low red blood cell
count (anemia) or a high red blood cell count (erythrocytosis) may accompany kidney cancer. Occasionally,
patients will have high calcium levels.
If the doctor suspects kidney cancer, an intravenous pyelogram (IVP) may be ordered. An IVP is an
x-ray test in which a dye in injected into a vein in the
arm. The dye travels through the body, and when it is
concentrated in the urine to be discharged, it outlines
the kidneys, ureters, and the urinary bladder. On an
x-ray image, the dye will reveal any abnormalities of the
urinary tract. The IVP may miss small kidney cancers.
Renal ultrasound is a diagnostic test in which
sound waves are used to form an image of the kidneys.
GALE ENCYCLOPEDIA OF MEDICINE

Kidney cancer

2000s. There is a strong association between cigarette
smoking and kidney cancer. Cigarette smokers are
twice as likely as non-smokers are to develop kidney
cancer. Working around coke ovens has been shown
to increase people’s risk of developing this cancer.
Certain types of painkillers that contain the chemical
phenacetin are associated with kidney cancer. The
United States government discontinued use of analgesics containing phenacetin about 20 years ago. Obesity
may be yet another risk factor for kidney cancer. Some
studies show a loose association between kidney cancer and occupational exposure to cadmium, petroleum
products, lead, dry-cleaning solvents, trichloroethylene (TCE), and asbestos. Other risk factors for the
development of kidney cancer include Hispanic heritage and preexisting von Hippel-Lindau disease.

An extracted cancerous kidney. (Custom Medical Stock Photo.
Reproduced by permission.)

Ultrasound is a painless and non-invasive procedure
that can be used to detect even very small kidney
tumors. Imaging tests such as computed tomography
scans (CT scans) and magnetic resonance imaging
(MRI) can be used to evaluate the kidneys and the
surrounding organs. These tests are used to check
whether the tumor has spread outside the kidney to
other organs in the abdomen. If the patient complains
of bone pain, a special x ray called a bone scan may be
ordered to rule out spread to the bones. A chest x ray
may be taken to rule out spread to the lungs.
A kidney biopsy is used to positively confirm the
diagnosis of kidney cancer. During this procedure, a
small piece of tissue is removed from the tumor and
examined under a microscope. The biopsy will give
information about the type of tumor, the cells that
are involved, and the aggressiveness of the tumor
(tumor stage).

Treatment
Each person’s treatment is different and depends
on several factors. The location, size, and extent of the
tumor have to be considered in addition to the
patient’s age, general health, and medical history. In
addition, much has changed in the treatment and
management of kidney cancer since the 1980s, including new surgical techniques, new anticancer drugs, and
the development of effective treatments for advanced
disease.
The primary treatment for kidney cancer that has
not spread to other parts of the body, which is a Stage
I, II, or III tumor, is surgical removal of the diseased
kidney (nephrectomy). Because most cancers affect
only one kidney, the patient can function well with
the remaining one. Two types of surgical procedure
2117

Kidney cancer

are used. Radical nephrectomy removes the entire
kidney and the surrounding tissue. Sometimes, the
lymph nodes surrounding the kidney are also
removed. Partial nephrectomy removes only part of
the kidney along with the tumor. This procedure is
used either when the tumor is very small or when it is
not practical to remove the entire kidney. It is not
practical to remove a kidney when the patient has
only one kidney or when both kidneys have tumors.
There is a small (5%) chance of missing some of the
cancer. Nephrectomy can also be useful for Stage IV
cancers, but alternative surgical procedures such as
transarterial angioinfarction may be used.
The rapid development and widespread use of
laparoscopic techniques has made it possible for surgeons to remove small tumors while sparing the rest of
the kidney. Most tumors removed by laparoscopy are
4 cm (1.6 in) in size or smaller. Laparoscopy also
allows the surgeon to remove small tumors with cryoablation (destroying the tumor by freezing it) rather
than cutting.
Radiation therapy, which consists of exposing the
cancer cells to high-energy gamma rays from an external source, generally destroys cancer cells with minimal damage to the normal tissue. Side effects are
nausea, fatigue, and stomach upsets. These symptoms
disappear when the treatment is over. In kidney cancer, radiation therapy has been shown to alleviate pain
and bleeding, especially when the cancer is inoperable.
However, it has not proven to be of much use in
destroying the kidney cancer cells. Therefore radiation
therapy is not used very often as a treatment for
cancer or as a routine adjuvant to nephrectomy.
Radiotherapy, however, is used to manage metastatic
kidney cancer.
Treatment of kidney cancer with anticancer drugs
(chemotherapy) has not produced good results.
However, new drugs and new combinations of drugs
continue to be tested in clinical trials. One new drug,
semaxanib (SU5416), is reported to have good results
in treating patients with kidney cancer. As of 2004,
however, semaxanib is still undergoing clinical trials in
the United States.
Immunologic therapy (or immunotherapy), a
form of treatment in which the body’s immune system
is harnessed to help fight the cancer, is a new mode of
therapy that is being tested for kidney cancer. Clinical
trials with substances produced by the immune cells
(aldesleukin and interferon) have shown some promise
in destroying kidney cancer cells. These substances
have been approved for use but they can be very
toxic and produce severe side effects. The benefits
2118

KEY TERMS
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Bone scan—An x-ray study in which patients are
given an intravenous injection of a small amount
of a radioactive material that travels in the
blood. When it reaches the bones, it can be
detected by x ray to make a picture of their
internal structure.
Chemotherapy—Treatment with anticancer drugs.
Computed tomography (CT) scan—A medical procedure in which a series of x-ray images are made
and put together by a computer to form detailed
pictures of areas inside the body.
Cryoablation—A technique for removing tissue by
destroying it with extreme cold.
Hematuria—Blood in the urine.
Immunotherapy—Treatment of cancer by stimulating the body’s immune defense system.
Intravenous pyelogram (IVP)—A procedure in
which a dye is injected into a vein in the arm. The
dye travels through the body and concentrates in
the urine to be discharged. It outlines the kidneys,
ureters, and the urinary bladder. An x-ray image is
then made and any abnormalities of the urinary
tract are revealed.
Magnetic resonance imaging (MRI)—A medical
procedure used for diagnostic purposes in which
pictures of areas inside the body can be created
using a magnet linked to a computer.
Nephrectomy—A medical procedure in which the
kidney is surgically removed.
Radiation therapy—Treatment with high-energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Renal ultrasound—A painless and non-invasive
procedure in which sound waves are bounced off
the kidneys. These sound waves produce a pattern
of echoes that are then used by the computer to
create pictures of areas inside the kidney
(sonograms).

derived from the treatment have to be weighed very
carefully against the side effects in each case.
Immunotherapy is the most promising systemic therapy for metastatic kidney cancer.
GALE ENCYCLOPEDIA OF MEDICINE

Because kidney cancer is often caught early and
sometimes progresses slowly, the chances of a surgical
cure are good. Length of survival depends on the size
of the original tumor, the aggressiveness of the specific
cells making up the tumor, and whether the cancer
cells spread from the kidney to surrounding or distant
tissues.
Kidney cancer is also one of the few cancers for
which there are well-documented cases of spontaneous
remission without therapy. Unfortunately, recurrences can occur even as long as ten years after the
original diagnosis and treatment, and cancer can also
crop up in the other, previously unaffected kidney.

Prevention
The exact cause of kidney cancer is not known, so
it is not possible to prevent all cases. However, because
a strong association between kidney cancer and
tobacco has been shown, avoiding tobacco is the best
way to lower one’s risk of developing this cancer.
Using care when working with cancer-causing agents
such as asbestos and cadmium and eating a wellbalanced diet may also help prevent kidney cancer.

SU5416 (Semaxanib) in a Patient with Probable von
Hippel-Lindau Syndrome.’’ Urologic Oncology
22 (May–June 2004): 193–196.
Lam, J. S., O. Svarts, and A. J. Pantuck. ‘‘Changing
Concepts in the Surgical Management of Renal Cell
Carcinoma.’’ European Urology 45 (June 2004):
692–705.
Lotan, Y., D. A. Duchene, J. A. Cadeddu, et al. ‘‘Changing
Management of Organ-Confined Renal Masses.’’
Journal of Endourology 18 (April 2004): 263–268.
Moon, T. D., F. T. Lee, Jr., S. P. Hedican, et al.
‘‘Laparoscopic Cryoablation under Sonographic
Guidance for the Treatment of Small Renal Tumors.’’
Journal of Endourology 18 (June 2004): 436–440.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, N.E., Atlanta,
GA 30329. (800) 227-2345. <http://www.cancer.org>.
Cancer Research Institute (National Headquarters). 681
Fifth Avenue, New York, NY 10022. (800) 992-2623.
<http://www.cancerresearch.org>.
National Cancer Institute (NCI). 9000 Rockville Pike,
Building 31, Room 10A16, Bethesda, MD 20892. (800)
422-6237. <http://www.nci.nih.gov>.
National Kidney Cancer Association. 1234 Sherman
Avenue, Suite 203, Evanston, IL 60202-1375. (800)
850-9132.
National Kidney Foundation. 30 East 33rd Street, New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.

Resources

Rosalyn Carson-DeWitt, MD
Rebecca Frey, PhD

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Renal Cell Carcinoma (Hypernephroma;
Adenocarcinoma of the Kidney).’’ Section 17, Chapter
233 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Quek, Marcus L., and John P. Stein. ‘‘Malignant Tumors of
the Urogenital Tract.’’ In Conn’s Current Therapy 2001.
53th ed. Philadlphia: W.B. Saunders Company, 2001.
PERIODICALS

Brauch, H., G. Weirich, B. Klein, et al. ‘‘VHL Mutations in
Renal Cell Cancer: Does Occupational Exposure to
Trichloroethylene Make a Difference?’’ Toxicology
Letters 151 (June 15, 2004): 301–310.
Dutcher, J.P. ‘‘Immunotherapy: Are We Making a
Difference?’’ Current Opinion in Urology September
2000: 435–9.
Godley, P.A., and K.I. Ataga. ‘‘Renal Cell Carcinoma.’’
Current Opinion in Oncology May 2000: 260–4.
Griffiths, T. R., and J. K. Mellon. ‘‘Evolving
Immunotherapeutic Strategies in Bladder and Renal
Cancer.’’ Postgraduate Medical Journal 80 (June 2004):
320–327.
Jennens, R. R., M. A. Rosenthal, G. J. Lindeman, and
M. Michael. ‘‘Complete Radiological and Metabolic
Response of Metastatic Renal Cell Carcinoma to
GALE ENCYCLOPEDIA OF MEDICINE

Kidney dialysis see Dialysis, kidney

Kidney disease
Definition
Kidney disease is a general term for any damage
that reduces the functioning of the kidney. Kidney
disease is also called renal disease.

Description
The kidneys are a pair bean-shaped, fist-sized
organs that are located below the rib cage near the
middle of the back. In adults they filter about 200
quarts (190 L) of blood every day to remove waste
products that result from the normal activities of tissues in the body. These wastes circulate in the blood.
and if not removed they would damage the body. The
kidneys also play a crucial role in regulating the
amount of water and chemicals (electrolytes) in
2119

Kidney disease

Prognosis

Kidney disease

the body such
phosphorous.

as

sodium,

potassium

and

Inside the kidneys are about one million tiny units
called nephrons. Inside each nephron is a very thin
blood vessel called a capillary that twists around a very
thin tube called a tubule. This combination of capillary
and tubule inside the nephron is called a glomerulous
and it is here that the blood is filtered. Water, electrolytes, and waste products (but not red blood cells) can
pass across the capillary wall and into the tubule. The
kidney then regulates how much water and which other
substances can pass back into the blood in the capillary
to keep the body in balance. Waste products, excess
water, and excess electrolytes remain in the tubule and
eventually leave the body as urine.
The kidneys also release three regulatory chemicals—erythropoietin, renin, and calcitriol—that affect
other functions in the body. Erythropoietin stimulates
the bone marrow to produce new red blood cells.
Renin helps regulate blood pressure, and calcitriol is
a form of vitamin D and is important in maintaining
bones and the level of calcium in the body.
Because the kidney has many functions, there are
many types of kidney disease. Congenital kidney diseases are disorders that are present at birth. Polycystic
kidney disease (PKD) is a rare disorder in which children inherit defective genes from both parents that
cause cysts full of fluid to develop in the kidneys and
replace the blood filtering units. As a result, the kidneys cannot adequately remove wastes from the body.
There are two other types of PDK. One is inherited,
but does not appear until adulthood, and the other
develops as a result of long-term kidney damage. In
total, about half a million people in the United States
have some form of PKD. Hereditary disease and birth
defects are the most common causes of kidney disease
in children up to age 14.
Acute kidney diseases are problems that develop
suddenly. Many acute kidney diseases can be cured,
but some may cause permanent damage. Common
acute kidney diseases include kidney infection, hemolytic uremic syndrome, nephrotic syndrome in children,
and damage caused by injury to the kidney or poisoning. Hemolytic uremic syndrome is a rare disease that
usually affects children under age ten and is caused by
eating food contaminated with bacteria. The bacteria
release a poison that damages the kidney and causes
acute kidney failure. Most children who develop this
disease recover and their kidney function returns to
normal.
Chronic kidney disease is disease that is slow to
develop and usually does not show any symptoms
2120

until kidney damage is permanent. The National
Kidney and Urologic Disease Information
Clearinghouse, a federal agency, estimates that about
4.5% of people over age 20 have chronic kidney disease as indicated by tests that measure kidney function. The most common cause of chronic kidney
disease in the United States is diabetes. It accounts
for between 33% and 40% of all new cases of chronic
kidney disease in the United States. In diabetes, the
body cannot break down glucose (sugar). This extra
glucose in the blood damages the nephrons so that
they no longer filter blood effectively.
High or uncontrolled blood pressure (hypertension) is the second leading cause of chronic kidney
disease. It accounts for between 27% and 30% of all
new cases of chronic kidney disease. High blood pressure damages the capillaries in the nephron, so that
they can no longer work with the tubules to filter the
blood. Glomerulonephtitis is a term for several different chronic kidney diseases where damage to the
nephrons causes protein or red blood cells pass into
the urine. Kidney cancer is uncommon, accounting for
only 2% of cancer cases.
Over-the-counter analgesics (pain medications)
such as aspirin, acetaminophen (Tylenol), ibuprofen
(Advil), naxopren sodium (Aleve), and similar medications that can be bought without a prescription may
make kidney disease worse in individuals who already
have kidney damage or cause kidney damage in
healthy individuals who take these medications daily
for several years. The chance of damage is increased
when these pain medications are taken in combination
with each other or with caffeine or codeine (Some
painkilling tablets are a combination of pain medications and caffeine or codeine). Individuals who take
these painkillers regularly or who have been told they
have kidney damage should discuss the risk of these
medications with their physician.
Chronic kidney disease can lead to end-stage renal
disease (ESRD), in which there is almost total failure
of the kidneys. If renal function is reduced to only 25%
of normal, serious illness results. When this drops to
10–15% of normal, death occurs unless the individual
receives dialysis or a kidney transplant. In 2002, there
were over 100,300 new cases of ESRD, 44% of which
were caused by diabetes. Treatment of ESRD in the
United States cost about $25.2 billion in 2002.

Causes & symptoms
Causes of kidney disease are many and varied.
Leading causes are diabetes, high blood pressure,
inherited disease, and infection. Acute kidney disease
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Simple blood and urine tests can indicated kidney
disease, but more extensive testing may be needed to
determine the exact nature of the disease. A blood test
that measures serum creatinine, a waste product, can
indicate how well the kidneys are working. Although
normal levels of creatinine vary (an average range is
0.6–1.2 mg/dL), a higher than expected level in the
blood may indicate kidney damage. A blood urea
nitrogen (BUN) blood test measures waste products
circulating in the blood. Normal levels range from
7%–20 mg/dL. The less well the kidney is working,
the higher the BUN.
A 24-hour urine collection test will accurately
measure how much urine the kidneys are producing
in a day. A urinalysis can determine if protein or red
blood cells are leaking into the urine indicating abnormal kidney function. A creatinine clearance test compares the amount of creatinine in a 24-hour urine
sample with the amount of creatinine in the blood to
determine how much blood the kidneys are filtering
each minute.
Based on the results of blood and urine tests, other
tests such as a CT scan, MRI, or kidney biopsy may be
ordered.

excreted in urine. Eating more foods such as bananas,
dried beans and peas, nuts, and potatoes that are high
in potassium or taking a potassium supplement pill
help reverse this effect. When protein is found in the
urine, some physicians recommend reducing the
amount of protein (mainly found in meat) in the diet.
When kidneys fail completely in ESRD, there are
only two alternatives: dialysis or kidney transplant.
There are two types of dialysis. Peritoneal dialysis
uses a membrane in the individual’s abdomen to filter
waste products. The most common kind of peritoneal
dialysis is continuous ambulatory peritoneal dialysis
(CAPD), in which the individual is hooked up to a bag
of dialysis fluid that he carries with him, allowing
continuous dialysis. The fluid is changed four times a
day. In another form of peritoneal dialysis, the abdomen is filled with dialysis fluid. Wastes filter into the
fluid for several hours often while the individual is
asleep, the then the fluid is drained from the body.
Peritoneal dialysis can be done at home without the
need for a health care professional.
In hemodialysis, the individual must go to a dialysis center about three times a week. His blood is sent
through a machine that filters out the waste and then
returns the cleansed blood to his body. The process
takes three to four hours and is done by a health care
professional.
Kidney transplants can come from either a living
donor or a deceased donor. Donors are matched with
recipients based on blood type and must take drugs to
prevent their immune system from rejecting the kidney
after transplantation. The United Network for Organ
Sharing (UNOS) coordinates matching donor kidneys
with appropriate recipients. As of 2005, over 100 clinical trials were enrolling patients with various types of
kidney disease. Information on current clinical trials
can be found at <http://www.clinicaltrials.gov>.

Treatment
Most treatment for kidney disease involves treating the underlying cause of the disease, such as controlling high blood pressure or diabetes. Diuretic
medication (‘‘water pills’’) may be given to help relieve
fluid accumulation. Antibiotics are used to treat kidney infections. Other drugs may be given to treat
specific kidney diseases.
Diet and lifestyle changes are an important part of
controlling kidney disease. Obesity increases blood
pressure, so losing weight can help limit kidney
damage, as can stopping smoking. Reducing sodium
(salt) in the diet also helps control blood pressure. In
certain kinds of kidney disease, potassium is removed
in abnormally large quantities by the kidneys and
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
Alternative treatments tend to focus on removing
excess water from the body, but have limited effect on
serious disease. Asparagus (Asparagus officinalis) birch
tea(Betula species), goldenrod infusion(Solidago
species), horsetail Equisetum arvense), and stinging
nettle (Urtica dioica) all are used to stimulate urine
production.

Prognosis
Many individuals recover normal kidney function
after developing acute kidney disease, although in
some cases, such as poisoning and injury, kidney
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Kidney disease

is often marked by a lack of urination and increased
fluid build up in the body. Chronic kidney disease is
often called a ‘‘silent’’ killer, because no obvious
symptoms develop until the kidneys are permanently
damaged. The National Kidney Foundation estimated in 2005 that 20 million Americans had undetected moderate chronic kidney disease. Chronic
kidney disease most often results from other diseases
such as diabetes or hypertension.

Kidney function tests

KEY TERMS

United Network for Organ Sharing (UNOS). P. O. Box
13770, Richmond, VA 23225. Telephone: 804-3308500. <http://www.unos.org>.

Congenital—Present at birth.

OTHER

Diuretic—A substance that stimulates the kidney to
excrete water.

‘‘Your Kidneys and How They Work.’’ National Kidney
and Urologic Disease Clearinghouse. July 2003 [cited
23 March 2005]. <http://www.kidney.niddke.nih.gov/
kudiseases/pubs/yourkidneys/index.htm#rate>.
‘‘Kidney Disease Overview.’’ National Kidney Disease
Education Program. 9 March 2005 [cited 23 March
2005]. <http://www.nkdep.nih.gov/patientspublic/
kindeydiseaseoverview.htm#4>.

Glomerulous—A twisted mass of blood capillaries
and urine tubules in the kidney where filtering of
waste products occurs.
Hormone—A chemical produced by living cells
that travels through the circulatory system and
affects tissue at some distance from where it was
released.
Hypertension—High blood pressure.
Nephron—The smallest functional unit of the kidney involved in the removal of waste products and
excess water from the blood.

damage may be permanent. Chronic kidney disease
tends to get progressively worse as the individual
ages. More than 15,000 kidney transplants are done
each year, and there is a often long waiting list for
donated kidneys. As of 2001 (last year for which statistics were available), 80.6% of individuals receiving a
transplant from a deceased donor survived for at least
5 years, and 90.4% of individuals receiving a kidney
donated from a living donor survived for at least
5 years.

Prevention
Maintaining a healthy body weight, getting regular exercise, and not smoking all promote kidney
health. Controlling underlying diseases such as diabetes and high blood pressure are important in preventing chronic kidney diseases.
Resources

Tish Davidson, A.M.

Kidney failure see Acute kidney failure;
Chronic kidney failure

Kidney function tests
Definition
Kidney function tests is a collective term for a
variety of individual tests and procedures that can be
done to evaluate how well the kidneys are functioning.

Purpose
The kidneys, the body’s natural filtration system,
perform many vital functions, including removing
metabolic waste products from the bloodstream, regulating the body’s water balance, and maintaining
the pH (acidity/alkalinity) of the body’s fluids.
Approximately one and a half quarts of blood per
minute are circulated through the kidneys, where
waste chemicals are filtered out and eliminated from
the body (along with excess water) in the form of urine.
Kidney function tests help to determine if the kidneys
are performing their tasks adequately.

ORGANIZATIONS

American Association of Kidney Patients. 3505 East
Frontage Road, Suite 315, Tampa, FL 33607.
Telephone: 800-749-2257. <http://www.aakp.org>.
American Foundation for Urologic Disease. 1128 North
Charles Street, Baltimore, MD 21201 Telephone:
800-242-2383. <http://www.afud.org>.
National Kidney Foundation. 30 East 33rd Street, New
York, NY 10016 Telephone: 800-622-9010. <http://
www.kidney.org>.
National Kidney and Urologic Disease Clearinghouse.
3 Information Way, Bethesda, MD 20892-3580.
Telephone: 800-891-5390. <http://www.niddk.nih.gov>.

2122

Precautions
A complete history should be taken prior to kidney function tests to assess the patient’s food and drug
intake. A wide variety of prescription and over-thecounter medications can affect blood and urine kidney
function test results, as can some food and beverages.

Description
Many conditions can affect the ability of the kidneys to carry-out their vital functions. Some lead to a
GALE ENCYCLOPEDIA OF MEDICINE

concentrate or dilute the urine. Kidneys that
are functioning normally will excrete more water
into the urine as fluid intake is increased, diluting
the urine. If fluid intake is decreased, the kidneys
excrete less water and the urine becomes more concentrated. The test may be done on a urine sample
collected first thing in the morning, on multiple
timed samples, or on a cumulative sample collected
over a twenty-four hour period. The patient will
typically be prescribed a high-protein diet for several
days before the test and asked to drink no fluids the
night before the test.

Urine tests
There are a variety of urine tests that assess kidney
function. A simple, inexpensive screening test, called a
routine urinalysis, is often the first test administered if
kidney problems are suspected. A small, randomly
collected urine sample is examined physically for
things like color, odor, appearance, and concentration
(specific gravity); chemically for substances such as
protein, glucose, and pH (acidity/ alkalinity); and
microscopically for the presence of cellular elements
(red blood cells, white blood cells, and epithelial cells),
bacteria, crystals, and casts (structures formed by the
deposit of protein, cells, and other substances in the
kidneys’ tubules). If results indicate a possibility of
disease or impaired kidney function, one or more of
the following additional tests is usually performed to
more specifically diagnose the cause and the level of
decline in kidney function.


Creatinine clearance test. This test evaluates how
efficiently the kidneys clear a substance called creatinine from the blood. Creatinine, a waste product of
muscle energy metabolism, is produced at a constant
rate that is proportional to the muscle mass of the
individual. Because the body does not recycle it, all of
the creatinine filtered by the kidneys in a given
amount of time is excreted in the urine, making
creatinine clearance a very specific measurement of
kidney function. The test is performed on a timed
urine specimen—a cumulative sample collected over
a two to twenty-four hour period. Determination of
the blood creatinine level is also required to calculate
the urine clearance.



Urea clearance test. Urea is a waste product that is
created by protein metabolism and excreted in the
urine. The urea clearance test requires a blood sample to measure the amount of urea in the bloodstream and two urine specimens, collected one hour
apart, to determine the amount of urea that is filtered, or cleared, by the kidneys into the urine.



Urine osmolality test. Urine osmolality is a measurement of the number of dissolved particles in urine. It
is a more precise measurement than specific gravity for evaluating the ability of the kidneys to

GALE ENCYCLOPEDIA OF MEDICINE



Urine protein test. Healthy kidneys filter all proteins
from the bloodstream and then reabsorb them,
allowing no protein, or only slight amounts of protein, into the urine. The persistent presence of significant amounts of protein in the urine, then, is an
important indicator of kidney disease. A positive
screening test for protein (included in a routine urinalysis) on a random urine sample is usually followed-up with a test on a 24-hour urine sample that
more precisely measures the quantity of protein.
Blood tests

There are also several blood tests that can aid in
evaluating kidney function. These include:


Blood urea nitrogen test (BUN). Urea is a by-product
of protein metabolism. This waste product is formed
in the liver, then filtered from the blood and excreted
in the urine by the kidneys. The BUN test measures
the amount of nitrogen contained in the urea. High
BUN levels can indicate kidney dysfunction, but
because blood urea nitrogen is also affected by protein intake and liver function, the test is usually done
in conjunction with a blood creatinine, a more specific indicator of kidney function.



Creatinine test. This test measures blood levels of
creatinine, a by-product of muscle energy metabolism that, like urea, is filtered from the blood by the
kidneys and excreted into the urine. Production of
creatinine depends on an individual’s muscle mass,
which usually fluctuates very little. With normal kidney function, then, the amount of creatinine in the
blood remains relatively constant and normal. For
this reason, and because creatinine is affected very
little by liver function, an elevated blood creatinine is
a more sensitive indication of impaired kidney function than the BUN.



Other blood tests. Measurement of the blood levels
of other elements regulated in part by the kidneys can
also be useful in evaluating kidney function. These
include sodium, potassium, chloride, bicarbonate,
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Kidney function tests

rapid (acute) decline in kidney function; others lead to
a gradual (chronic) decline in function. Both result in a
build-up of toxic waste substances in the blood. A
number of clinical laboratory tests that measure the
levels of substances normally regulated by the kidneys
can help determine the cause and extent of kidney
dysfunction. These tests are done on urine samples,
as well as on blood samples.

Kidney function tests

KEY TERMS
Blood urea nitrogen (BUN)—The nitrogen portion
of urea in the bloodstream. Urea is a waste product
of protein metabolism in the body.
Creatinine—The metabolized by-product of creatine, an organic acid that assists the body in producing muscle contractions. Creatinine is found in the
bloodstream and in muscle tissue. It is removed
from the blood by the kidneys and excreted in the
urine.
Osmolality—A measurement of urine concentration that depends on the number of particles dissolved in it. Values are expressed as milliosmols per
kilogram (mOsm/kg) of water.
Urea—A by-product of protein metabolism that is
formed in the liver. Because urea contains ammonia, which is toxic to the body, it must be quickly
filtered from the blood by the kidneys and excreted
in the urine.

calcium, magnesium, phosphorus, protein, uric acid,
and glucose.

imposed in preparation for some blood or urine tests
may trigger side-effects in some individuals.

Normal results
Normal values for many tests are determined by
the patient’s age and sex. Reference values can also
vary by laboratory, but are generally within the ranges
that follow.
Urine tests


Creatinine clearance. For a 24-hour urine collection,
normal results are 90-139 ml/min for adult males less
than 40 years old, and 80-125 ml/min for adult
females less than 40 years old. For people over 40,
values decrease by 6.5 ml/min for each decade of life.



Urea clearance. With maximum clearance, normal is
64–99 ml/min.



Urine osmolality. With restricted fluid intake (concentration testing), osmolality should be greater than
800 mOsm/kg of water. With increased fluid intake
(dilution testing), osmolality should be less than 100
mOSm/kg in at least one of the specimens collected.



Urine protein. A 24-hour urine collection should
contain no more than 150 mg of protein.

Preparation
Patients will be given specific instructions for collection of urine samples, depending on the test to be
performed. Some timed urine tests require an extended
collection period of up to 24 hours, during which time
the patient collects all urine voided and transfers it to a
specimen container. Refrigeration and/or preservatives
are typically required to maintain the integrity of such
urine specimens. Certain dietary and/or medication
restrictions may be imposed for some of the blood
and urine tests. The patient may also be instructed to
avoid exercise for a period of time before a test.

Aftercare
If medication was discontinued prior to a urine
kidney function test, it may be resumed once the test is
completed.

Risks
Risks for these tests are minimal, but may include
slight bleeding from a blood-drawing site, hematoma
(accumulation of blood under a puncture site), or
fainting or feeling light-headed after venipuncture. In
addition, suspension of medication or dietary changes
2124

Blood tests


Blood urea nitrogen (BUN). 8–20 mg/dl.



Creatinine. 0.8–1.2 mg/dl for males, and 0.6–0.9 mg/dl
for females.

Abnormal results
Low clearance values for creatinine and urea indicate diminished ability of the kidneys to filter these
waste products from the blood and excrete them in the
urine. As clearance levels decrease, blood levels of
creatinine and urea nitrogen increase. Since it can be
affected by other factors, an elevated BUN, by itself, is
suggestive, but not diagnostic, for kidney dysfunction.
An abnormally elevated blood creatinine, a more specific and sensitive indicator of kidney disease than the
BUN, is diagnostic of impaired kidney function.
Inability of the kidneys to concentrate the urine in
response to restricted fluid intake, or to dilute the
urine in response to increased fluid intake during
osmolality testing may indicate decreased kidney function. Because the kidneys normally excrete almost no
protein in the urine, its persistent presence, in amounts
that exceed the normal 24-hour urine value, usually
indicates some type of kidney disease as well.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010.<http://www.kidney.org>.

diseases. These radioactive materials (tracers) may
also be called radiopharmaceuticals, and they accumulate (collect) in specific organs in the body.
Radiopharmaceuticals are able to yield valuable information about the particular organ being studied.

Paula Anne Ford-Martin

Whether outside the body or inside the body,
tracers emit radioactive signals, called gamma rays,
which can be collected and counted by a special device,
called a gamma camera. The images of the kidney that
the camera produces are called renal scans.

Kidney nuclear medicine scan

The kidney nuclear medicine scan can be performed on an outpatient basis, usually by a nuclear
medicine technologist. The technologist helps prepare
the patient for the exam by positioning him or her on
an exam table or cart in the imaging area. The patient’s
position is usually flat on the back. The patient must
lie still during imaging to prevent blurring of the
images that will be taken. The technologist positions
the camera as close to the kidney (or kidneys) as
possible to obtain the best images.

Definition
A kidney nuclear medicine scan, or study, is a
simple outpatient test that involves administering
small amounts of radioactive substances, called tracers, into the body and then imaging the kidneys and
bladder with a special camera. The images obtained
can help in the diagnosis and treatment of certain
kidney diseases.

Purpose
While many tests, such as x rays, ultrasound
exams, or computed tomography scans (CT scans),
can reveal the structure of the kidneys (its anatomy),
the kidney nuclear medicine scan is unique in that it
reveals how the kidneys are functioning. This is valuable information in helping a doctor make a diagnosis.
Therefore, the kidney nuclear medicine scan is performed primarily to see how well the kidneys are
working and, at the same time, they can identify
some of the various structures that make up the
kidney.

Precautions
If a patient is pregnant, it is generally recommended that she not have a kidney nuclear medicine
scan. The unborn baby is more sensitive to radiation
than an adult. If a woman thinks she might be pregnant, she should inform her doctor of this too.
Women who are breastfeeding should also inform
their doctor. The doctor may recommend the woman
stop breastfeeding for a day or two after a kidney
nuclear medicine scan, depending on the particular
tracer that was used since the tracer can accumulate
in breast milk.

Description
Nuclear medicine is a branch of radiology that
uses radioactive materials to diagnose or treat various
GALE ENCYCLOPEDIA OF MEDICINE

In the next step of the procedure, the technologist
injects the radiopharmaceutical into the patient. This
may be done with one single injection or through an
intravenous (IV) line. Immediately after the tracer is
injected, imaging begins. It is important to obtain
images right away because the tracer’s radioactivity
begins to diminish (decay). The time required for onehalf of the tracer’s activity to decay is called the tracer’s half-life (T 1/2). The half-life is unique to each
radiopharmaceutical. Also, it is important to see the
kidney in its immediate state.
Serial pictures are taken with the gamma camera
and may be seen on a computer or TV-like screen. The
camera doesn’t emit radiation, it only records it. The
images then are stored on film.
A kidney nuclear medicine scan ranges from 45
minutes to three hours in length, depending on the
goals of the test. But the test typically takes about an
hour to an hour-and-a-half.
Once the images and curves are obtained, the
nuclear medicine physician or radiologist analyzes,
or reads, them. Various information can be provided
to the doctor through these, depending on the test that
was performed. A variety of kidney nuclear medicine
studies are available for a doctor to help in making
diagnoses. It is important to understand that kidney
nuclear medicine scans are good at identifying when
there is an abnormality, but they do not always identify the specific problem. They are very useful in providing information about how the various parts of the
kidneys function, which, in turn, can assist in making a
diagnosis.
2125

Kidney nuclear medicine scan

Resources

Kidney nuclear medicine scan
A computer-generated time activity curve generated from a renal scan. This time activity curve looks at the radiation count over
a period of time. (Photograph by Collette Placek. Reproduced by permission.)

Studies may be performed to determine the rate
at which the kidney’s are filtering a patient’s blood.
These studies use a radiopharmaceutical, called
Technetium DTPA (Tc 99m DTPA). This radiopharmaceutical also can identify obstruction (blockage) in
the collecting system. To study how well the tubules
and ducts of the kidney are functioning, the radiopharmaceutical Technetium MAG3 is used. Studying
tubular function is a good indicator of overall renal
function. In many renal diseases, one of the first things
that disappears or diminishes is the tubular function.
Candidates for a kidney nuclear medicine scan are
patients who have:


Renal failure or chronic renal failure



Obstruction in their urine collection systems



Renal artery stenosis



A kidney transplant.

Preparation
No preparation is necessary for a kidney nuclear
medicine scan. The doctor may ask the patient to
refrain from certain medications, however, before the
scan if the medications might interfere with the test.
For example, if a scan is being performed to study
renal artery stenosis, the patient may have to refrain
from taking medications for hypertension.

Aftercare
Patients can resume their normal daily activities
immediately after the test. Most tracers are passed
2126

KEY TERMS
Intravenous pyelogram (IVP)—X ray technique
using dye to image the kidneys, ureters, and
bladder.
Renal—Having to do with the kidneys.
Renal artery stenosis—Narrowing or constriction
of the artery that supplies the kidney with blood.

naturally from the body, though drinking fluids after
a kidney nuclear medicine scan can help flush the
tracer into the urine and out of the body more quickly.

Risks
Nuclear medicine procedures are very safe. Unlike
some of the dyes that may be used in x-ray studies,
radioactive tracers rarely cause side effects. There are
no long-lasting effects of the tracers themselves,
because they have no functional effects on the body’s
tissues.

Normal results
The test reveals normal kidney function for age
and medical situation.

Abnormal results
The test reveals a change in function that may be
attributable to a disease process, such as obstruction
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

Society of Nuclear Medicine. 1850 Samuel Morse Dr.,
Reston, VA 10016. (703) 708-9000. <http://
www.snm.org>.

Collette L. Placek

tubes, the presence of a stone will make these muscular
tubes spasm, causing severe pain.
About 10% of all people will have a kidney stone
in his or her lifetime. Kidney stones are most common
among:


Caucasians



Males



People over the age of 30



People who have had kidney stones previously



Relatives of kidney stone patients

Kidney removal see Nephrectomy
Causes and symptoms

Kidney stones
Definition

Kidney stones can be composed of a variety of
substances. The most common types of kidney stones
include:


Calcium stones. About 80% of all kidney stones fall
into this category. These stones are composed of
either calcium and phosphate, or calcium and oxalate. People with calcium stones may have other diseases that cause them to have increased blood levels
of calcium. These diseases include primary parathyroidism, sarcoidosis, hyperthyroidism, renal tubular
acidosis, multiple myeloma, hyperoxaluria, and
some types of cancer. A diet heavy in meat, fish,
and poultry can cause calcium oxalate stones.



Struvite stones. About 10% of all kidney stones fall
into this category. This type of stone is composed of
magnesium ammonium phosphate. These stones
occur most often when patients have had repeated
urinary tract infections with certain types of bacteria.
These bacteria produce a substance called urease,
which increases the urine pH and makes the urine
more alkaline and less acidic. This chemical environment allows struvite to settle out of the urine, forming stones.



Uric acid stones. About 5% of all kidney stones fall
into this category. Uric acid stones occur when
increased amounts of uric acid circulate in the bloodstream. When the uric acid content becomes very
high, it can no longer remain dissolved and solid
bits of uric acid settle out of the urine. A kidney
stone is formed when these bits of uric acid begin to
cling to each other within the kidney, slowly growing
into a solid mass. About half of all patients with this
type of stone also have deposits of uric acid elsewhere
in their body, commonly in the joint of the big toe.
This painful disorder is called gout. Other causes of
uric acid stones include chemotherapy for cancer,
certain bone marrow disorders where blood cells

Kidney stones are solid accumulations of material
that form in the tubal system of the kidney. Kidney
stones cause problems when they block the flow of
urine through or out of the kidney. When the stones
move along the ureter, they cause severe pain.

Description
Urine is formed by the kidneys. Blood flows into
the kidneys, and specialized tubes (nephrons) within
the kidneys allow a certain amount of fluid from the
blood, and certain substances dissolved in that fluid,
to flow out of the body as urine. Sometimes, a problem
causes the dissolved substances to become solid again.
Tiny crystals may form in the urine, meet, and cling
together to create a larger solid mass called a kidney
stone.
Many people do not ever find out that they have
stones in their kidneys. These stones are small enough
to allow the kidney to continue functioning normally,
never causing any pain. These are called ‘‘silent
stones.’’ Kidney stones cause problems when they
interfere with the normal flow of urine. They can
block (obstruct) the flow down the tube (the ureter)
that carries urine from the kidney to the bladder. The
kidney is not accustomed to experiencing any pressure. When pressure builds from backed-up urine,
the kidney may swell (hydronephrosis). If the kidney
is subjected to this pressure for some time, it may cause
damage to the delicate kidney structures. When the
kidney stone is lodged further down the ureter, the
backed-up urine may also cause the ureter to swell
(hydroureter). Because the ureters are muscular
GALE ENCYCLOPEDIA OF MEDICINE

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Kidney stones

or a malfunctioning kidney. If the test is abnormal, the
patient may be recalled another day for a repeat study,
performed differently, to narrow the list of causes.

Kidney stones

after injecting iodine dye into a vein is usually a more
reliable way of seeing a stone. This procedure is called
an intravenous pyelogram (IVP). The dye ‘‘lights up’’
the urinary system as it travels. In the case of an
obstruction, the dye will be stopped by the stone or
will only be able to get past the stone at a slow trickle.

X ray of kidney stone. (Custom Medical Stock Photo.
Reproduced by permission.)

are over-produced, and an inherited disorder called
Lesch-Nyhan syndrome.


Cystine stones. About 2% of all kidney stones fall
into this category. Cystine is a type of amino acid,
and people with this type of kidney stone have an
abnormality in the way their bodies process amino
acids in the diet.

Patients who have kidney stones usually do not
have symptoms until the stones pass into the ureter.
Prior to this, some people may notice blood in their
urine. Once the stone is in the ureter, however, most
people will experience bouts of very severe pain. The
pain is crampy and spasmodic, and is referred to as
‘‘colic.’’ The pain usually begins in the flank region,
the area between the lower ribs and the hip bone. As
the stone moves closer to the bladder, a patient will
often feel the pain radiating along the inner thigh. In
women, the pain may be felt in the vulva. In men, the
pain may be felt in the testicles. Nausea, vomiting,
extremely frequent and painful urination, and obvious
blood in the urine are common. Fever and chills
usually means that the ureter has become obstructed,
allowing bacteria to become trapped in the kidney
causing a kidney infection (pyelonephritis).

Diagnosis
Diagnosing kidney stones is based on the patient’s
history of the very severe, distinctive pain associated
with the stones. Diagnosis includes laboratory examination of a urine sample and an x-ray examination.
During the passage of a stone, examination of the
urine almost always reveals blood. A number of
x-ray tests are used to diagnose kidney stones. A
plain x ray of the kidneys, ureters, and bladder may
or may not reveal the stone. A series of x rays taken
2128

When a patient is passing a kidney stone, it is
important that all of his or her urine is strained
through a special sieve. This is to make sure that the
stone is caught. The stone can then be sent to a special
laboratory for analysis so that the chemical composition of the stone can be determined. After the kidney
stone has been passed, other tests will be required in
order to understand the underlying condition that
may have caused the stone to form. Collecting urine
for 24 hours, followed by careful analysis of its chemical makeup, can often determine a number of reasons
for stone formation.

Treatment
A patient with a kidney stone will say that the
most important aspect of treatment is adequate pain
relief. Because the pain of passing a kidney stone is so
severe, narcotic pain medications (like morphine) are
usually required. It is believed that stones may pass
more quickly if the patient is encouraged to drink large
amounts of water (2–3 quarts per day). If the patient is
vomiting or unable to drink because of the pain, it may
be necessary to provide fluids through a vein. If symptoms and urine tests indicate the presence of infection,
antibiotics will be required.
Although most kidney stones will pass on their
own, some will not. Surgical removal of a stone may
become necessary when a stone appears too large to
pass. Surgery may also be required if the stone is
causing serious obstructions, pain that cannot be treated, heavy bleeding, or infection. Several alternatives
exist for removing stones. One method involves inserting a tube into the bladder and up into the ureter.
A tiny basket is then passed through the tube, and an
attempt is made to snare the stone and pull it out.
Open surgery to remove an obstructing kidney stone
was relatively common in the past, but current methods allow the stone to be crushed with shock waves
(called lithotripsy). These shock waves may be aimed
at the stone from outside of the body by passing the
necessary equipment through the bladder and into the
ureter. The shock waves may be aimed at the stone
from inside the body by placing the instrument
through a tiny incision located near the stone. The
stone fragments may then pass on their own or may
be removed through the incision. All of these methods
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Kidney
Inferior
vena cava
Abdominal
aorta

A patient’s prognosis depends on the underlying
disorder causing the development of kidney stones. In
most cases, patients with uncomplicated calcium stones
will recover very well. About 60% of these patients,
however, will have other kidney stones. Struvite stones
are particularly dangerous because they may grow
extremely large, filling the tubes within the kidney.
These are called staghorn stones and will not pass out
in the urine. They will require surgical removal. Uric
acid stones may also become staghorn stones.

Stone

Prevention
Ureter

Common
iliac artery

Common
iliac vein

Stone

Bladder

Kidney stones can occur in the ureter near the bladder or
kidney. (Illustration by Argosy Inc.)

reduce the patient’s recovery time considerably when
compared to the traditional open operation.

Prevention of kidney stones depends on the type of
stone and the presence of an underlying disease. In almost
all cases, increasing fluid intake so that a person consistently drinks several quarts of water a day is an important
preventative measure. Patients with calcium stones may
benefit from taking a medication called a diuretic, which
has the effect of decreasing the amount of calcium passed
in the urine. Eating less meat, fish, and chicken may be
helpful for patients with calcium oxalate stones. Other
items in the diet that may encourage calcium oxalate
stone formation include beer, black pepper, berries, broccoli, chocolate, spinach, and tea. Uric acid stones may
require treatment with a medication called allopurinol.
Struvite stones will require removal and the patient
should receive an antibiotic. When a disease is identified
as the cause of stone formation, treatment specific to that
disease may lessen the likelihood of repeated stones.
Resources
ORGANIZATIONS

American Foundation for Urologic Disease. 300 West Pratt
St., Baltimore, MD 21201-2463. (800) 242-2383.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010.<http://www.kidney.org>.

Rosalyn Carson-DeWitt, MD

Alternative treatment
Alternative treatments for kidney stones include the
use of herbal medicine, homeopathy, acupuncture, acupressure, hypnosis, or guided imagery to relieve pain.
Starfruit (Averrhoa carambola) is recommended to
increase the amount of urine a patient passes and to
relieve pain. Dietary changes can be made to reduce the
risk of future stone formation and to facilitate the resorption of existing stones. Supplementation with magnesium, a smooth muscle relaxant, can help reduce pain
and facilitate stone passing. Homeopathy and herbal
GALE ENCYCLOPEDIA OF MEDICINE

Kidney transplantation
Definition
Kidney transplantation is a surgical procedure to
remove a healthy, functioning kidney from a living or
2129

Kidney transplantation

medicine, both western and Chinese, recommend a number of remedies that may help prevent kidney stones.

Kidney transplantation

National Transplant Waiting List By Organ Type (June 2000)

Organ Needed

Number Waiting

Kidney
Liver
Heart
Lung
Kidney-Pancreas
Pancreas
Heart-Lung
Intestine

48,349
15,987
4,139
3,695
2,437
942
212
137

brain-dead donor and implant it into a patient with
non-functioning kidneys.

Purpose
Kidney transplantation is performed on patients
with chronic kidney failure, or end-stage renal disease
(ESRD). ESRD occurs when a disease or disorder
damages the kidneys so that they are no longer capable
of adequately removing fluids and wastes from the
body or of maintaining the proper level of certain
kidney-regulated chemicals in the bloodstream.
Without long-term dialysis or a kidney transplant,
ESRD is fatal.

Precautions
Patients with a history of heart disease, lung disease, cancer, or hepatitis may not be suitable candidates for receiving a kidney transplant.

Description
Kidney transplantation involves surgically attaching a functioning kidney, or graft, from a brain-dead
organ donor (a cadaver transplant) or from a living
donor, to a patient with ESRD. Living donors may be
related or unrelated to the patient, but a related donor
has a better chance of having a kidney that is a stronger biological ‘‘match’’ for the patient.
The surgical procedure to remove a kidney from a
living donor is called a nephrectomy. The kidney donor
is administered general anesthesia and an incision is
made on the side or front of the abdomen. The blood
vessels connecting the kidney to the donor are cut and
clamped, and the ureter is also cut between the bladder
and kidney and clamped. The kidney and an attached
section of ureter is removed from the donor. The
vessels and ureter in the donor are then tied off and
2130

the incision is sutured together again. A similar procedure is used to harvest cadaver kidneys, although
both kidneys are typically removed at once, and blood
and cell samples for tissue typing are also taken.
Laparoscopic nephrectomy is a form of minimally-invasive surgery using instruments on long,
narrow rods to view, cut, and remove the donor
kidney. The surgeon views the kidney and surrounding tissue with a flexible videoscope. The videoscope
and surgical instruments are maneuvered through
four small incisions in the abdomen. Once the kidney
is freed, it is secured in a bag and pulled through a
fifth incision, approximately 3 in (7.6 cm) wide, in the
front of the abdominal wall below the navel.
Although this surgical technique takes slightly longer
than a traditional nephrectomy, preliminary studies
have shown that it promotes a faster recovery time,
shorter hospital stays, and less post-operative pain
for kidney donors.
Once removed, kidneys from live donors and
cadavers are placed on ice and flushed with a cold
preservative solution. The kidney can be preserved in
this solution for 24–48 hours until the transplant takes
place. The sooner the transplant takes place after harvesting the kidney, the better the chances are for
proper functioning.
During the transplant operation, the kidney recipient patient is typically under general anesthesia and
administered antibiotics to prevent possible infection.
A catheter is placed in the bladder before surgery
begins. An incision is made in the flank of the patient
and the surgeon implants the kidney above the pelvic
bone and below the existing, non-functioning kidney
by suturing the kidney artery and vein to the patient’s
iliac artery and vein. The ureter of the new kidney is
attached directly to the bladder of the kidney recipient.
Once the new kidney is attached, the patient’s existing,
diseased kidneys may or may not be removed, depending on the circumstances surrounding the kidney
failure.
Since 1973, Medicare has picked up 80% of
ESRD treatment costs, including the costs of transplantation for both the kidney donor and recipient.
Medicare also covers 80% of immunosuppressive
medication costs for up to three years, although federal legislation was under consideration in early 1998
that may remove the time limit on these benefits. To
qualify for Medicare ESRD benefits, a patient must be
insured or eligible for benefits under Social Security,
or be a spouse or child of an eligible American. Private
insurance and state Medicaid programs often cover
the remaining 20% of treatment costs.
GALE ENCYCLOPEDIA OF MEDICINE

Kidney transplantation

New kidney
Iliac vein
Iliac artery

Bladder

Kidney transplantation involves the surgical attachment of a functioning kidney, or graft, from a donor to a patient with endstage renal disease (ESRD). During the procedure, the surgeon makes an incision in the patient’s flank and implants the new
kidney above the pelvic bone and below the non-functioning kidney by suturing the kidney artery and vein to the patient’s iliac
artery and vein. The ureter of the new kidney is then attached directly to the bladder of the patient. (Illustration by Electronic
Illustrators Group.)

Preparation
Patients with chronic renal disease who need a
transplant and do not have a living donor register
with United Network for Organ Sharing (UNOS)
will be placed on a waiting list for a cadaver kidney
transplant. UNOS is a non-profit organization that is
under contract with the federal government to
administer the Organ Procurement and Transplant
Network (OPTN) and the national Scientific
Registry of Transplant Recipients (SR). Kidney
availability is based on the patient’s health status.
The most important factor is that the kidney be compatible to the patient’s body. A human kidney has a
set of six antigens, substances that stimulate the production of antibodies. (Antibodies then attach to
cells they recognize as foreign and attack them.)
Donors are tissue-matched for 0 to 6 of the antigens,
and compatibility is determined by the number and
GALE ENCYCLOPEDIA OF MEDICINE

strength of those matched pairs. Patients with a living
donor who is a close relative have the best chance of a
close match.
Potential kidney donors undergo a complete medical history and physical examination to evaluate their
suitability for donation. Extensive blood tests are performed on both donor and recipient. The blood samples are used to tissue type for antigen matches, and
confirm that blood types are compatible. A panel of
reactive antibody (PRA) is performed by mixing white
blood cells from the donor and serum from the recipient to ensure that the recipient antibodies will not
have a negative reaction to the donor antigens. A urine
test is performed on the donor to evaluate his kidney
function. In some cases, a special dye that shows up on
x rays is injected into an artery, and x rays are taken to
show the blood supply of the donor kidney (a procedure called an arteriogram).
2131

Kidney transplantation
A human kidney is being prepped by medical personnel prior to transplantation. (Photograph by Brad Nelson, Custom Medical
Stock Photo. Reproduced by permission.)

Once compatibility is confirmed and the physical
preparations for kidney transplantation are complete,
both donor and recipient may undergo a psychological or psychiatric evaluation to ensure that they are
emotionally prepared for the transplant procedure
and aftercare regimen.

Aftercare
Kidney donors and recipients will experience
some discomfort in the area of the incision. Pain relievers are administered following the transplant operation. Patients may also experience numbness, caused
by severed nerves, near or on the incision.
A regimen of immunosuppressive, or anti-rejection,
medication is prescribed to prevent the body’s immune
system from rejecting the new kidney. Common immunosuppressants include cyclosporine, prednisone, and
azathioprine. The kidney recipient will be required to
take immunosuppressants for the life span of the
new kidney. Intravenous antibodies may also be
administered after transplant surgery. Daclizumab, a
monoclonal antibody, is a promising new therapy that
2132

can be used in conjunction with standard immunosuppressive medications to reduce the incidence of
organ rejection.
Transplant recipients may need to adjust their
dietary habits. Certain immunosuppressive medications cause increased appetite or sodium and protein
retention, and the patient may have to adjust his or her
intake of calories, salt, and protein to compensate.

Risks
As with any surgical procedure, the kidney transplantation procedure carries some risk for both a living donor and a graft recipient. Possible complications
include infection and bleeding (hemorrhage). The
most common complication for kidney recipients is a
urine leak. In approximately 5% of kidney transplants, the ureter suffers some damage, which results
in the leak. This problem is usually correctable with
follow-up surgery.
The biggest risk to the recovering transplant recipient is not from the operation or the kidney itself, but
from the immunosuppressive medication he or she
GALE ENCYCLOPEDIA OF MEDICINE

Arteriogram—A diagnostic test that involves viewing the arteries and/or attached organs by injecting
a contrast medium, or dye, into the artery and taking an x ray.
Dialysis—A blood filtration therapy that replaces the
function of the kidneys, filtering fluids and waste
products out of the bloodstream. There are two
types of dialysis treatment—hemodialysis, which
uses an artificial kidney, or dialyzer, as a blood filter;
and peritoneal dialysis, which uses the patient’s
abdominal cavity (peritoneum) as a blood filter.
Iliac artery—Large blood vessel in the pelvis that
leads into the leg.
Immunosuppressive medication—Drugs given to a
transplant recipient to prevent his or her immune
system from attacking the transplanted organ.
Rejection—The process in which the immune system attacks tissue it sees as foreign to the body.
Videoscope—A surgical camera.

must take. Because these drugs suppress the immune
system, the patient is susceptible to infections such as
cytomegalovirus (CMV) and varicella (chickenpox).
The immunosuppressants can also cause a host of
possible side effects, from high blood pressure to
osteoporosis. Prescription and dosage adjustments
can lessen side effects for some patients.

Normal results
The new kidney may start functioning immediately,
or may take several weeks to begin producing urine.
Living donor kidneys are more likely to begin functioning earlier than cadaver kidneys, which frequently suffer
some reversible damage during the kidney transplant
and storage procedure. Patients may have to undergo
dialysis for several weeks while their new kidney establishes an acceptable level of functioning.
The success of a kidney transplant graft depends on
the strength of the match between donor and recipient
and the source of the kidney. Cadaver kidneys have a
four-year survival rate of 66%, compared to an 80.9%
survival rate for living donor kidneys. However, there
have been cases of cadaver and living, related donor
kidneys functioning well for over 25 years.
Studies have shown that after they recover from
surgery, kidney donors typically have no long-term
GALE ENCYCLOPEDIA OF MEDICINE

complications from the loss of one kidney, and their
remaining kidney will increase its functioning to compensate for the loss of the other.

Abnormal results
A transplanted kidney may be rejected by the
patient. Rejection occurs when the patient’s immune
system recognizes the new kidney as a foreign body and
attacks the kidney. It may occur soon after transplantation, or several months or years after the procedure has
taken place. Rejection episodes are not uncommon in the
first weeks after transplantation surgery, and are treated
with high-dose injections of immunosuppressant drugs. If
a rejection episode cannot be reversed and kidney failure
continues, the patient will typically go back on dialysis.
Another transplant procedure can be attempted at a later
date if another kidney becomes available.
Resources
ORGANIZATIONS

American Association of Kidney Patients. 100 S. Ashley
Drive, #280, Tampa, FL 33602. (800) 749-2257.
<http://www.aakp.org>.
American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://www.arbon.com/kidney>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010.<http://www.kidney.org>.
United Network for Organ Sharing (UNOS). 1100 Boulders
Parkway, Suite 500, P.O. Box 13770, Richmond, VA
23225-8770. (804) 330-8500. <http://www.unos.org>.
United States Renal Data System (USRDS). The University of
Michigan, 315 W. Huron, Suite 240, Ann Arbor, MI 48103.
(734) 998-6611. <http://www.med.umich.edu/usrds>.
OTHER

Transweb. <http://www.transweb.org>.

Paula Anne Ford-Martin

Kidney ultrasound see Abdominal ultrasound

Kidney, ureter, and bladder
x-ray study
Definition
A kidney, ureter, and bladder (KUB) x-ray study
is an abdominal x ray. Despite its name, KUB does not
show the ureters and only sometimes shows the kidneys and bladder and, even then, with uncertainty.
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Kidney, ureter, and bladder x-ray study

KEY TERMS

Kidney, ureter, and bladder x-ray study

KEY TERMS
Ureteral stent—A surgical device implanted in
patients with damaged ureters that holds the ureter
open so that urine can flow freely from the kidneys
to the bladder.

Description
A KUB is typically a single x-ray procedure. The
patient lies flat on his back on an x-ray table. An x-ray
plate is placed underneath him near the small of the
back, and the x-ray camera is aimed at his abdomen.
The patient is asked to hold his breath and lie still
while the x ray is taken. Sometimes a second KUB
will be ordered, with the patient standing, or if unable
to do so, lying on his side.

Preparation
A KUB study requires no special diet, fluid
restrictions, medications, or other preparation. The
patient is typically required to wear a hospital gown
or similar attire and to remove all jewelry so the x-ray
camera has an unobstructed view of the abdomen.
A lead apron may be placed over the abdominal
areas of the body not being x rayed to shield the
patient from unnecessary radiation.
An x-ray image of a human torso and abdomen showing a
blocked ureter. (Custom Medical Stock Photo. Reproduced by
permission.)

Aftercare
No special aftercare treatment or regimen is
required for a KUB study.

Purpose
The KUB study is a diagnostic test used to detect
kidney stones and to diagnose some gastrointestinal
disorders. The KUB is also used as a follow-up procedure after the placement of devices such as ureteral
stents and nasogastric or nasointestinal tubes (feeding
tubes) to verify proper positioning.

Precautions
Because of the risks of radiation exposure to the
fetus, pregnant women are advised to avoid this x-ray
procedure.
A KUB study is a preliminary screening test for
kidney stones, and should be followed by a more sophisticated series of diagnostic tests [such as an abdominal
ultrasound, intravenous urography, or computed tomography scan (CT scan)] if kidney stones are suspected.
2134

Risks
Because the KUB study is an x-ray procedure, it
does involve minor exposure to radiation.

Normal results
Normal KUB x-ray films show two kidneys of a
similar size and shape. A normal amount of intestinal
gas is seen.

Abnormal results
Abnormal KUB films may show calculi (kidney
stones). If both kidneys are visible, it may be possible
to diagnose renal size discrepancies. The films may
also show too much bowel gas indicating possible
obstruction or soft tissue masses.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Paula Anne Ford-Martin

Kinesiology, applied
Definition
Kinesiology is a series of tests that locate weaknesses in specific muscles reflecting imbalances
throughout the body. Then specific massages or acupressure techniques are used in an attempt to rebalance what has been revealed by the kinesiology tests.
Thus, kinesiology is used as both an assessment tool
and as a limited therapeutic modality.

Purpose
Kinesiology claims to be a healing system that
detects and corrects imbalances in the body before
they develop into a disease, and which restores overall
system balance and harmony. It is used to alleviate
muscle, bone, and joint problems, treat all manner of
aches and pains, and correct many areas of imbalance
and discomfort.

Precautions
Since interpretation of the muscle tests is both
complex and subjective, it should only be performed
by a licensed health professional trained to look for
‘‘subclinical’’ symptoms (those which have not yet
become a major problem). Kinesiology, itself, is
more of a diagnostic technique and should not be
thought of as a cure for any particular problem.

Description
Traditionally, the word ‘‘kinesiology’’ refers simply to the study of muscles and body movement. In
1964, however, American chiropractor George J.
Goodheart founded what has become known as
applied kinesiology when he linked oriental ideas
about energy flow in the body with western techniques
of muscle testing. First, Goodheart noted that all
muscles are related to other muscles. He observed
that for each movement a muscle makes, there is
another muscle or group of muscles involved with
GALE ENCYCLOPEDIA OF MEDICINE

that movement; one muscle contracts while another
one relaxes. So when he was presented with a painful,
overly-tight muscle, he would observe and treat the
opposite, and necessarily weak, muscle to restore balance. This was then a very new technique.
Further, Goodheart argued that there is a definite
and real connection between muscles, glands, and
organs, and that by testing the strength of certain
muscles he could learn about the health or condition
of the gland or organ to which it was related.
Applied kinesiology is based on the idea that the
body is an interacting unit made of different parts that
interconnect and affect each other. Everything we do
affects the body as a whole; therefore, a problem in
one area can cause trouble in another area. According
to kinesiology, the muscles eventually register and
reflect anything that is wrong with any part of the
body, whether physical or mental. Thus, a particular
digestive problem might show up in the related and
corresponding muscles of the legs. By testing the
strength of certain muscles, the kinesiologist claims
to be able to gain access to the body’s communication
system, and, thus, to read the health status of each of
the body’s major components.
The manual testing of muscles or muscle strength
is not new, and was used in the late 1940s to evaluate
muscle function and strength and to assess the extent
of an injury. Applied kinesiology measures whether a
muscle is stuck in the ‘‘on’’ position, acting like a tense
muscle spasm, or is stuck ‘‘off,’’ appearing weak or
flaccid. It is called manual testing because it is done
without instruments, using only the kinesiologist’s
fingertip pressure. During the first and longest
appointment, which lasts about an hour, the kinesiologist conducts a complete consultation, asking about
the patient’s history and background. During the physical examination, patients sit or lie down, then the
kinesiologist holds the patient’s leg or arm to isolate
a particular muscle. The practitioner then touches a
point on the body which he believes is related to that
muscle, and, with quick, gentle, and painless pressure,
pushes down on the limb. Patients are asked to resist
this pressure, and, if they cannot, an imbalance is
suspected in the related organ, gland, or body part.
This diagnostic technique uses muscles to find the
cause of a problem, and is based on traditional
Chinese medicine and its idea that the body has common energy meridians, or channels, for both organs
and muscles. Kinesiologists also claim that they are
able to locate muscle weaknesses that stem from a
variety of causes such as allergies, mineral and vitamin
deficiencies, as well as from problems with the lymph
system. Once the exact cause is determined, the
2135

Kinesiology, applied

Resources

Klinefelter syndrome

KEY TERMS
Acupressure—A form of acupuncture in which certain points of the body are pressed with the fingers
and hands to release energy blocks.
Alleviate—To make something easier to be
endured.
Complementary—Something that serves to fill out
or complete something else.
Deficiency—A shortage of something necessary for
health.
Diagnostic—The art or act of identifying a disease
from its signs and symptoms.
Flaccid—Flabby, limp, weak.
Meridian—In traditional Chinese medicine, the
channels which run beneath the skin through
which the body’s energy flows.
Spasm—An involuntary, sudden, violent contraction of a muscle or a group of muscles.

kinesiologist uses his fingertips to work the appropriate corresponding acupressure points in order to rebalance the flow of energy and restore health. Often he
will recommend a complementary program of nutrition therapy.

Klinefelter syndrome
Definition
Klinefelter syndrome is a chromosomal disorder
that affects only males. People with this condition are
born with at least one extra X chromosome. The syndrome was first identified and described in 1942 by
Harry Fitch Klinefelter, Jr., an American physician.

Description
Klinefelter syndrome is a condition in which one
or more extra X chromosomes are present in a male.
Boys with this condition appear normal at birth. They
enter puberty normally, but by mid puberty have low
levels of testosterone causing small testicles and the
inability to make sperm. Affected males may also have
learning disabilities and behavior problems such as
shyness and immaturity, and an increased risk for
certain other health problems.
Klinefelter syndrome is one of the most common
chromosomal abnormalities. About 1 in every 500 to
800 males is born with this disorder; approximately
3000 affected boys are born each year in the United
States. About 3% of the infertile male population have
Klinefelter syndrome. The condition appears to affect
all racial and ethnic groups equally.

Causes and symptoms
Risks
There are no major risks associated with this gentle, noninvasive therapy. It is generally safe for people
of all ages and has no side effects.

Normal results
If applied kinesiology does what it claims, patients
should expect muscle testing to discover the cause of
their physical complaint and to be told how to correct it.
Resources
ORGANIZATIONS

International College of Applied Kinesiology. 6405 Metcalf
Ave., Suite 503, Shawnee Mission, KS 66202. (913) 3845336. <http://www.icakusa.com> and <http://
www.icak.com>.

Leonard C. Bruno, PhD

Kleine-Levin syndrome see Sleep disorders
2136

Chromosomes are found in the cells in the body.
Chromosomes contain genes, structures that tell the
body how to grow and develop. Chromosomes are
responsible for passing on hereditary traits from parents to child. Chromosomes also determine whether
the child will be male or female. Normally, a person
has a total of 46 chromosomes in each cell, two of
which are responsible for determining that individual’s sex. These two sex chromosomes are called
X and Y. The combination of these two types of
chromosomes determines the sex of a child. Females
have two X chromosomes (the XX combination);
males have one X and one Y chromosome (the XY
combination).
In Klinefelter syndrome, a problem very early in
development results in an abnormal number of chromosomes. About 60% of embryos with Klinefelter
syndrome do not survive the fetal period. Most commonly, a male with Klinefelter syndrome will be born
with 47 chromosomes in each cell, rather than the
normal number of 46. The extra chromosome is an
X chromosome. This means that rather than having
GALE ENCYCLOPEDIA OF MEDICINE

Approximately 1/3 of all males with Klinefelter
syndrome have other chromosomal abnormalities
involving an extra X chromosome. Mosaic Klinefelter
syndrome occurs when some of the cells in the body
have an extra X chromosome and the others have
normal male chromosomes. These males can have the
same or milder symptoms than non-mosaic Klinefelter
syndrome. Males with more than one additional extra
X chromosome, such as 48,XXXY, are usually more
severely affected than males with 47,XXY.
Klinefelter syndrome is not considered an inherited condition. The risk of Klinefelter syndrome reoccurring in another pregnancy is not increased above
the general population risk.
The symptoms of Klinefelter syndrome are variable and not every affected person will have all of the
features of the condition. Males with Klinefelter syndrome appear normal at birth and have normal male
genitalia. From childhood, males with Klinefelter syndrome are taller than average with long limbs.
Approximately 20–50% have a mild intention tremor,
an uncontrolled shaking. Many males with Klinefelter
syndrome have poor upper body strength and can be
clumsy. Klinefelter syndrome does not cause homosexuality. Approximately 1/3 of males with Klinefelter
syndrome have gynecomastia or breast growth, some
requiring breast reduction surgery.
Most boys enter puberty normally, though some
can be delayed. The Leydig cells in the testicles usually
produce testosterone. With Klinefelter syndrome, the
Leydig cells fail to work properly causing the testosterone production to slow. By mid-puberty, testosterone production is decreased to approximately half of
normal. This can lead to decreased facial and pubic
hair growth. The decreased testosterone also causes an
increase in two other hormones, follicle stimulating
hormone (FSH) and luteinizing hormone (LH).
Normally, FSH and LH help the immature sperm
cells grow and develop. In Klinefelter syndrome,
there are few or no sperm cells. The increased amount
of FSH and LH causes hyalinization and fibrosis, the
growth of excess fibrous tissue, in the seminiferous
tubules, where the sperm are normally located. As
a result, the testicles appear smaller and firmer than
normal. With rare exception, men with Klinefelter
syndrome are infertile because they can not make
sperm.
While it was once believed that all boys with
Klinefelter syndrome are mentally retarded, doctors
GALE ENCYCLOPEDIA OF MEDICINE

now know that the disorder can exist without retardation. However, children with Klinefelter syndrome
frequently have difficulty with language, including
learning to speak, read, and write. Approximately
50% of males with Klinefelter syndrome are dyslexic.
Some people with Klinefelter syndrome have difficulty with social skills and tend to be more shy,
anxious, or immature than their peers. They can also
have poor judgment and do not handle stressful situations well. As a result, they often do not feel comfortable in large social gatherings. Some people with
Klinefelter syndrome can also have anxiety, nervousness and/or depression.
The greater the number of X chromosomes present, the greater the disability; each extra X chromosome lowers the child’s IQ by about 15 points. Boys
with several extra X-chromosomes have distinctive
facial features, more severe retardation, deformities
of bony structures, and even more disordered development of male features.

Diagnosis
Diagnosis of Klinefelter syndrome is made by
examining chromosomes for evidence of more than
one X chromosome present in a male. This can be
done in pregnancy with prenatal testing such as a
chorionic villus sampling or amniocentesis. Chorionic
villus sampling is a procedure done early in pregnancy
(approximately 10–12 weeks) to obtain a small sample
of the placenta for testing. An amniocentesis is done
further along in pregnancy (from approximately
16–18 weeks) to obtain a sample of fluid surrounding
the baby for testing. Both procedures have a risk of
miscarriage. Usually these procedures are done for a
reason other than diagnosing Klinefelter syndrome.
For example, a prenatal diagnostic procedure may be
done on an older woman to determine if her baby has
Down syndrome. If the diagnosis of Klinefelter syndrome is suspected in a young boy or adult male,
chromosome testing can also be on a small blood or
skin sample after birth.
Many men with Klinefelter syndrome go through
life without being diagnosed. The two most common
complaints leading to diagnosis of the condition are
gynecomastia and infertility.

Treatment
There is no treatment available as of the early
2000s to change a person’s chromosomal makeup.
Children with Klinefelter syndrome may benefit
from speech therapy for speech problems or other
2137

Klinefelter syndrome

the normal XY combination, the male has an XXY
combination. Because people with Klinefelter syndrome have a Y chromosome, they are all male.

Klinefelter syndrome

KEY TERMS
Chromosome—A microscopic thread-like structure found within each cell of the body and consists
of a complex of proteins and DNA. Humans have
46 chromosomes arranged into 23 pairs. Changes
in either the total number of chromosomes or their
shape and size (structure) may lead to physical or
mental abnormalities.
Gonadotrophin—Hormones that stimulate the
ovary and testicles.
Gynecomastia—Excessive growth of breast tissue
in males.
Leydig cells—Cells that make up the endocrine
tissue of the testis and produce testosterone. They
are named for Franz von Leydig (1821–1908), the
German professor of anatomy who first identified
them.
Testosterone—Hormone produced in the testicles
that is involved in male secondary sex
characteristics.

educational interventions for learning disabilities.
Testosterone injections started around the time
of puberty may help to produce more normal
development including more muscle mass, hair
growth and increased sex drive. Testosterone supplementation will not increase testicular size, decrease
breast growth or correct infertility. Psychiatric consultation may be helpful when the boy reaches
adolescence.
Some doctors recommend mastectomy as a surgical treatment for gynecomastia, on the grounds that
the enlarged breasts are often socially stressful for
affected males and significantly increase their risk of
breast cancer.

Prognosis
While many men with Klinefelter syndrome go on
to live normal lives, nearly 100% of these men will be
sterile (unable to produce a child). However, a few
men with Klinefelter syndrome have been reported
who have fathered a child through the use of assisted
fertility services.
Males with Klinefelter syndrome have an
increased risk of several systemic conditions, including
epilepsy, osteoporosis, such autoimmune disorders as
2138

lupus and arthritis, diabetes, and breast and germ
cell tumors. One Danish study reported in 2004 that
men with Klinefelter’s syndrome have a slightly shortened life span, dying about 2.1 years earlier than men
without the syndrome.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Chromosomal Abnormalities.’’ Section 19, Chapter
261 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Infertility.’’ Section 18, Chapter 245 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Probasco, Teri, and Gretchen A. Gibbs. Klinefelter
Syndrome. Richmond, IN: Prinit Press, 1999.
PERIODICALS

Bojesen, A., S. Juul, N. Birkebaek, and C. H. Gravholt.
‘‘Increased Mortality in Klinefelter Syndrome.’’
Journal of Clinical Endocrinology and Metabolism 89
(August 2004): 3830–3834.
Chen, Harold, MD. ‘‘Klinefelter Syndrome.’’ eMedicine
December 17, 2004. <http://emedicine.com/ped/
topic1252.htm>.
Diamond, M., and L. A. Watson. ‘‘Androgen Insensitivity
Syndrome and Klinefelter’s Syndrome: Sex and
Gender Considerations.’’ Child and Adolescent
Psychiatric Clinics of North America 13 (July 2004):
623–640.
Grosso, S., M. A. Farnetani, R. M. Di Bartolo, et al.
‘‘Electroencephalographic and Epileptic Patterns in X
Chromosome Anomalies.’’ Journal of Clinical
Neurophysiology 21 (July-August 2004): 249–253.
Lanfranco, F., A. Kamischke, M. Zitzmann, and E.
Nieschlag. ‘‘Klinefelter’s Syndrome.’’ Lancet 364 (July
17, 2004): 273–283.
Tyler, C., and J. C. Edman. ‘‘Down Syndrome, Turner
Syndrome, and Klinefelter Syndrome: Primary Care
throughout the Life Span.’’ Primary Care 31
(September 2004): 627–648.
ORGANIZATIONS

Klinefelter’s Organization. PO Box 60, Orpington,
BR68ZQ. UK. <http://hometown.aol.com/KSCUK/
index.htm>.
Klinefelter Syndrome and Associates, Inc. PO Box 119,
Roseville, CA 95678-0119. (916) 773-2999 or (888) 9999428. Fax: (916) 773-1449. ksinfo@genetic.org.
<http://www.genetic.org/ks>.
National Organization for Rare Disorders (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT 068131968. (203) 744-0100. Fax: (203) 798-2291. <http://
www.rarediseases.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Klinefelter Syndrome Support Group Home Page. <http://
klinefeltersyndrome.org/index.html>.

Carin Lea Beltz, MS
Rebecca J. Frey, PhD

Knee injuries
Definition
The five most common knee problems are arthritis, tendonitis, bruises, cartilage tears, and damaged
ligaments. Knee injuries can be caused by accidents,
impact, sudden or awkward movements, and gradual
wear and tear of the knee joint.

Description
Because the knee joint is both vulnerable and used
extensively in many activities, it is prone to injuries.
The American Academy of Orthopaedic Surgeons
estimates that 19.5 million visits to doctors’ offices in
2002 were for knee problems. In some sports including
football, skiing, and gymnastics, and racket sports,
injury rates to avid practitioners can near 50 percent,
and knee injuries are the most common reason
patients visit orthopedic doctors. An estimated one
in five runners gets a knee injury. The majority of
knee injuries, however, are minor and do not require
intensive treatment.
The knee, the largest joint in the body, connects
the thighbone (femur) to the lower leg (tibia). It is a
complex and efficient joint consisting of ligaments,
cartilage, and the bone of the kneecap (patella). All
of these parts can be injured. Inside the knee joint is
synovial fluid that protects and lubricates the parts,
which during injuries may increase and cause swelling.
The bursa are sacs in the knee that contain synovial
fluid and provide cushioning and lubrication.
Four ligaments comprise the knee joint. The medial collateral ligament (MCL) runs along the inside of
the knee, while the lateral collateral ligament (LCL) is
on the outside of the knee. The cruciate ligaments
cross inside the knee. The anterior cruciate ligament
(ACL) is deep inside the knee and limits rotation of the
joint. The posterior cruciate ligament (PCL) is also
inside the knee and limits the backward movement of
the joint. Ligaments in the knee can be partially or
completely torn, depending on the extent of the injury.
GALE ENCYCLOPEDIA OF MEDICINE

The minisci cartilage are two thin, oval-shaped
tissues that act as cushions between the ends of the
leg bones. The medial miniscus is the cartilage closest
to the other leg while the lateral miniscus is nearer the
outside of the knee. Injuries to the minisci include tears
from injuries and impact and degenerative wearing
away of the structure. The minisci can be partially or
completely torn during injury.
The bones around the knee, including the kneecap, can be broken, fractured, or chipped. The patellar
tendon connects the kneecap to the shinbone, while
the quadriceps tendon connects the quadriceps muscle
to the patella. The patellar tendon can be torn or can
develop injury and pain from degeneration. It can also
be fully dislocated or partially dislocated (called subluxation). The tendons in the knee may develop pain
and inflammation known as tendonitis.
The bones of the knee joint are covered with tissue
known as articular cartilage. This cartilage can be
injured or fractured, and can also develop a degenerative condition called chondromalacia. Osteoarthritis is
the pain associated with the wearing down of this
cartilage.

Causes & symptoms
Arthritis may develop from an auto-immune disorder, known as rheumatoid arthritis, or may be
caused by the gradual wear and tear of the joint,
known as osteoarthritis. Symptoms of arthritis in the
knee include pain ranging from dull aches to severe
pain, and may be accompanied by swelling and range
of movement loss. Arthritic symptoms may tend to be
worst in the morning and decrease throughout the day
as the knee is used. Arthritis can be caused by lupus,
Lyme disease, and other infections. Knee swelling also
may be caused by bursitis, the inflammation of the
bursa.
Cartilage injuries may include chondromalacia,
with symptoms including dull pain and pain while
climbing stairs. Damage to the minisci cartilage often
occurs from sudden twists, forceful plants, and awkward movements. A torn cartilage may make a popping sound, and may be accompanied by mild to
severe pain, particularly while straightening the leg.
Swelling, stiffening, and loss of movement are also
symptoms of cartilage tears, as are clicking sounds
and friction in the knee during movement.
Ligament injuries may cause dull or severe pain,
swelling, loss of the range of movement of the joint,
and loss of the stability and strength of the knee.
Ligament injuries typically occur from strong blows
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Knee injuries

OTHER

Knee injuries

and forces applied to the knee. Injuries to the MCL are
the most common, often caused by impact to the side
of the knee joint. Of the cruciate ligaments, the PCL is
less commonly injured than the ACL. Typically, the
PCL is injured by forceful blows to the knee, such as
during car accidents, while the ACL can be injured by
impacts and by sudden twists. Torn ligaments may be
accompanied by a popping sound indicating the rupture, and may not always cause pain, so that some of
them go unnoticed. Torn ligaments may weaken the
knee and cause buckling or folding under weight.
Tendon injuries range from tendonitis to torn
tendons. Symptoms of tendonitis include pain and
swelling, while ruptured tendons can cause more
intense pain, swelling, and loss of movement.
Osgood-Shlatter disease is a condition common in
young boys who play running and jumping sports.
Symptoms include inflammation of the patellar tendon and pain in the front of the knee during and after
strenuous activity.
Iliotibial band syndrome is common in running
and other repetitive sports, characterized by pain at
the side of the knee caused by stress on the band of
tendons there. Sometimes this condition causes a
snapping sensation when the knee is straightened.

Diagnosis
Depending on the severity of the condition, family
physicians or orthopedic physicians who specialize in
the knee joint may be consulted. If arthritis is suspected, a rheumatologist may be consulted. The diagnosis process includes taking a complete patient
history with details of the pain and the circumstances
of the injury. The physician will give the patient a
thorough physical examination, including utilizing several manual techniques of moving the knee joint and
legs in various positions to help determine the type of
injury. An experienced practitioner can often make an
accurate diagnosis of injuries by performing a
sequence of manual diagnostic tests.
Laboratory tests may be ordered to further or
clarify the diagnosis. X rays can show damage to
the bones as well as the narrowing of the knee space
that may imply cartilage problems. For more indepth diagnosis, a computerized axial tomographic
(CAT) scan is an x-ray technique that can provide
three-dimensional views of the bones in the knee. A
magnetic resonance imaging (MRI) scan gives a computerized portrait of the interior of the knee, and may
show damage to the ligaments and cartilage.
Arthroscopy is a form of minor surgery that inserts a
2140

tiny camera into the knee and gives a very accurate
view of the joint. Radionuclide scanning (bone scans)
use radioactive material injected into the bloodstream to monitor the blood flow in particular
areas. If infection or rheumatoid arthritis is suspected, a physician may order blood tests for diagnosis. Biopsies, in which pieces of tissue are
laboratory tested, may also be used for diagnosis.

Treatment
When a person suspects a knee injury, the first
treatment recommended is R.I.C.E., which stands for
rest, ice, compression, and elevation. First, the person
should cease the activity which caused the injury and
immediately rest and immobilize the joint. Ice may be
applied to reduce pain and swelling, and compression,
such as wraps and braces, may be used to immobilize
the knee. Elevating the leg is also helpful in reducing
swelling and aiding circulation. Immediate care will
prevent the worsening of the injury.
Treatment options for knee injuries can range
from rest and light activity, to physical therapy, to
surgery. Most knee injuries are treated with proper
rest, exercise, and strengthening programs recommended by physicians. For injuries that require surgery or deeper diagnosis, arthroscopy is the least
invasive technique and has a quick recovery time associated with the procedure. Arthroscopy is commonly
used to repair cartilage and partially torn ligaments.
For severe knee injuries, reconstructive surgery or open
knee surgery may be required. Full knee replacements
may also be performed for severely damaged knees.
After surgery, physical therapy programs for rehabilitation are recommended. Treatment for osteoarthritis
includes over-the-counter painkillers, exercise, and
weight reduction. For rheumatoid arthritis, more
powerful prescription medications, such as steroids
and stronger painkillers, and intensive physical therapy may be ordered. Knee injuries associated with
infection may require antibiotics.

Alternative treatment
Alternative therapies for knee injuries focus on
supporting the body’s ability to heal itself. Various
therapies may include bodywork and postural adjustments such as chiropractic and Rolfing work, in addition to physical therapy and gentle exercise routines.
Herbal remedies and nutritional supplements may be
used to aid the healing process and reduce symptoms.
Acupuncture may be used for pain relief, and yoga is a
low-impact exercise routine that increases flexibility,
good alignment, and strength.
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Kneecap removal

Lupus—Chronic inflammatory disease caused by
immune system disorder.
Lyme disease—Bacteria infection spread by ticks.
Orthopedist—Physician specializing in the diagnosis and treatment of problems involving the skeletal system.
Rheumatologist—Physician specializing in the
diagnosis and treatment of arthritis and related
conditions.

Prevention
The best prevention for knee injuries is being
aware of activities that carry high risks for knee injuries and acting carefully. The knees can be strengthened by evenly building the muscles in the quadriceps
and hamstrings. Increasing flexibility in the body
through stretching can also help reduce injuries.
Properly fitting shoes and other sports equipment are
essential for preventing injury as well. Finally, before
engaging in activities that stress the knee, a thorough
and gradual warm-up routine, including aerobic activity and stretching, will lessen the chances of knee
injury.
Resources
BOOKS

Grelsamer, Ronald, M.D. What Your Doctor May Not Tell
You about Knee Pain and Surgery. Warner Books, 2002.
Halpern, Brian. The Knee Crisis Handbook. Rodale Books,
2003.
Scott, W. Norman. Dr. Scott’s Knee Book. Fireside Books,
1996.
ORGANIZATIONS

American Academy of Orthopaedic Surgeons. P.O. Box
2058, Des Plaines, IL 60017. 800-824-BONE. <ttp://
www.aaos.org>.
National Athletic Trainers’ Association. 2952 Stemmons
Freeway, Dallas, TX 75247-6196. (214) 637-6282.
<http://www.nata.org>.
American Physical Therapy Association. 1111 North
Fairfax St., Alexandria, VA 22314-1488. (703) 6842782. <http://www.apta.org>.

Douglas Dupler

Knee replacement see Joint replacement
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Kneecap removal, or patellectomy, is the surgical
removal of the patella, commonly called the kneecap.

Purpose
Kneecap removal
circumstances:

is

done

under

three



When the kneecap is fractured or shattered



When the kneecap dislocates easily and repeatedly



When degenerative arthritis of the kneecap causes
extreme pain

A person of any age can break a kneecap in an
accident. When the bone is shattered beyond repair,
the kneecap is removed. No prosthesis or artificial
replacement part is put in its place.
Dislocation of the kneecap is most common in
young girls between the ages of 10-14. Initially, the
kneecap will pop back into place of its own accord, but
pain may continue. If dislocation occurs too often, or
the kneecap doesn’t go back into place correctly, the
patella may rub the other bones in the knee, causing an
arthritis-like condition. Some people are born with
birth defects that cause the kneecap to dislocate
frequently.
Degenerative arthritis of the kneecap, also called
patellar arthritis or chondromalacia patellae, can cause
enough pain that it is necessary to remove the kneecap.
As techniques of joint replacement have improved,
arthritis in the knee is more frequently treated with
total knee replacement.

Precautions
People who have had their kneecap removed for
degenerative arthritis and then later have to have a
total knee replacement are more likely to have problems with the stability of their artificial knee than
those who only have total knee replacement. This is
because the realigned muscles and tendons provide
less support once the kneecap is removed.

Description
Kneecap removal is performed under either general or local anesthesia at a hospital or freestanding
surgical center, by an orthopedic surgeon. The surgeon makes an incision around the kneecap. Then,
the muscles and tendons attached to the kneecap are
2141

Kneecap removal

KEY TERMS

KOH test

KEY TERMS
Degenerative arthritis, or osteoarthritis—A noninflammatory type of arthritis, usually occurring in
older people, characterized by degeneration of cartilage, enlargement of the margins of the bones, and
changes in the membranes in the joints.

cut and the kneecap is removed. Next, the muscles are
sewed back together, and the skin is closed with
sutures or clips that stay in place about one week.
Any hospital stay is generally brief.

Preparation
Prior to surgery, x rays and other diagnostic tests
are done on the knee to determine if removing the
kneecap is the appropriate treatment. Pre-operative
blood and urine tests are also done.

Aftercare
Pain relievers may be prescribed for a few days.
The patient will initially need to use a cane, or
crutches, to walk. Physical therapy exercises to
strengthen the knee should be begun immediately.
Driving should be avoided for several weeks. Full
recovery can take months.

Risks
Risks involved with kneecap removal are similar
to those that occur in any surgical procedure, mainly
allergic reaction to anesthesia, excessive bleeding, and
infection.

Normal results
People who have kneecap removal because of a
broken bone or repeated dislocations have the best
chance for complete recovery. Those who have this
operation because of arthritis may have less successful
results, and later need a total knee replacement.

KOH test
Definition
The KOH test takes its name from the chemical
formula for potassium hydroxide (KOH), which is the
substance used in the test. The test, which is also called
a potassium hydroxide preparation, is done to rapidly
diagnose fungal infections of the hair, skin, or nails. A
sample of the infected area is analyzed under a microscope following the addition of a few drops of potassium hydroxide.

Purpose
The primary purpose of the KOH test is the differential diagnosis of infections produced by dermatophytes and Candida albicans from other skin
disorders. Dermatophytes are a type of fungus that
invade the top layer of the skin, hair, or nails, and
produce an infection commonly known as ringworm,
technically known as tinea. It can appear as ‘‘jock itch’’
in the groin or inner thighs (tinea cruris); on the feet
(tinea pedis); on the scalp and hair (tinea capitis); and
on the nails (tinea unguium). Tinea versicolor appears
anywhere on the skin and produces characteristic
unpigmented patches. Tinea unguium affects the nails.
Similar symptoms of redness, scaling, and itching
can be caused by other conditions, such as eczema and
psoriasis. The KOH test is a quick, inexpensive test—
often done in a physician’s office—to see if these symptoms are caused by a dermatophyte. If a dermatophyte
is found, treatment is started immediately; further tests
are seldom necessary.
A yeast (candidal) infection of the skin or a
mucous membrane, such as the mouth, often produces
a white cheesy material at the infection site. This type
of infection, known as thrush, is also identified with
the KOH test.

Description

‘‘Kneecap Removal.’’ In The Complete Guide to Symptoms,
Illness and Surgery, edited by H. Winter Griffith, et al,
3rd ed. New York: Berkeley Publishing, 1995.

The KOH test involves the preparation of a slide
for viewing under the laboratory microscope. KOH
mixed with a blue-black dye is added to a sample from
the infected tissues. This mixture makes it easier to see
the dermatophytes or yeast under the microscope. The
KOH dissolves skin cells, hair, and debris; the dye
adds color. The slide is gently heated to speed up the
action of the KOH. Finally the slide is examined under
a microscope.

Tish Davidson, A.M.

Dermatophytes are easily recognized under the
microscope by their long branch-like structures.

Resources
BOOKS

2142

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Postgraduate Medicine February 1998: 191–192,
197–198, 200, 205.

Nancy J. Nordenson

Dermatophyte—A type of fungus that causes diseases of the skin, including tinea or ringworm.
KOH—The chemical formula for potassium hydroxide, which is used to perform the KOH test. The
tests is also called a potassium hydroxide
preparation.

Korsakoff’s psychosis see Korsakoff’s
syndrome

Thrush—A disease of the mouth, caused by
Candida albicans and characterized by a whitish
growth and ulcers. It can be diagnosed with the
KOH test.

Korsakoff’s syndrome

Tinea—A superficial infection of the skin, hair, or
nails, caused by a fungus and commonly known as
ringworm.

Definition
Korsakoff’s syndrome is a memory disorder
which is caused by a deficiency of vitamin B1, also
called thiamine.

Description
Yeast cells look round or oval. The dermatophyte that
causes tinea versicolor has a characteristic spaghettiand-meatballs appearance.
If the KOH test is done in the doctor’s office, the
results are usually available while the person waits. If
the test is sent to a laboratory, the results will be ready
the same or following day. The KOH test is covered by
insurance when medically necessary.

Preparation
The physician selects an infected area from which
to collect the sample. Scales and cells from the area are
scraped using a scalpel. If the test is to be analyzed
immediately, the scrapings are placed directly onto a
microscope slide. If the test will be sent to a laboratory, the scrapings are placed in a sterile covered
container.

Normal results
A normal, or negative, KOH test shows no fungi
(no dermatophytes or yeast).

Abnormal results
Dermatophytes or yeast seen on a KOH test indicate the person has a fungal infection. Follow-up tests
are usually unnecessary.
Resources
PERIODICALS

Crissey, John Thorne. ‘‘Common Dermatophyte Infections.
A Simple Diagnostic Test and Current Management.’’
GALE ENCYCLOPEDIA OF MEDICINE

In the United States, the most common cause of
thiamine deficiency is alcoholism. Other conditions
which cause thiamine deficiency occur quite rarely,
but can be seen in patients undergoing dialysis
(a procedure used primarily for patients suffering
from kidney failure, during which the patient’s blood
circulates outside of the body, is mechanically
cleansed, and then is circulated back into the body),
pregnant women with a condition called hyperemesis
gravidarum (a condition of extreme morning sickness,
during which the woman vomits up nearly all fluid and
food intake), and patients after surgery who are given
vitamin-free fluids for a prolonged period of time.
Thiamine deficiency is an important cause of disability
in developing countries where the main source of food
is polished rice (rice with the more nutritious outer
husk removed).
An associated disorder, Wernicke’s syndrome,
often precedes Korsakoff’s syndrome. In fact, they
so often occur together that the spectrum of symptoms
produced during the course of the two diseases is frequently referred to as Wernicke-Korsakoff syndrome.
The main symptoms of Wernicke’s syndrome include
ataxia (difficulty in walking and maintaining balance),
paralysis of some of the muscles responsible for movement of the eyes, and confusion. Untreated
Wernicke’s will lead to coma and then death.

Causes and symptoms
One of the main reasons that alcoholism leads to
thiamine deficiency has to do with the high-calorie
nature of alcohol. A person with a large alcohol intake
often, in essence, substitutes alcohol for other, more
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Korsakoff’s syndrome

KEY TERMS

Korsakoff’s syndrome

nutritive calorie sources. Food intake drops off considerably, and multiple vitamin deficiencies develop.
Furthermore, it is believed that alcohol increases the
body’s requirements for B vitamins, at the same time
interfering with the absorption of thiamine from the
intestine and impairing the body’s ability to store and
use thiamine. Direct neurotoxic (poisonous damage to
the nerves) effects of alcohol may also play some role.
Thiamine is involved in a variety of reactions which
provide energy to the neurons (nerve cells) of the brain.
When thiamine is unavailable, these reactions cannot
be carried out, and the important end-products of the
reactions are not produced. Furthermore, certain other
substances begin to accumulate, and are thought to
cause damage to the vulnerable neurons. The area of
the brain believed to be responsible for the symptoms of
Korsakoff’s syndrome is called the diencephalon, specifically the structures called the mamillary bodies and
the thalamus.
An individual with Korsakoff’s syndrome displays
much difficulty with memory. The main area of memory
affected is the ability to learn new information. Usually,
intelligence and memory for past events is relatively
unaffected, so that an individual may remember what
occurred 20 years previously, but is unable to remember
what occurred 20 minutes ago. This memory defect is
referred to as anterograde amnesia, and leads to a peculiar symptom called ‘‘confabulation,’’ in which a person
suffering from Korsakoff’s fills in the gaps in his or her
memory with fabricated or imagined information. For
instance, a person may insist that a doctor to whom he
or she has just been introduced is actually an old high
school classmate, and may have a lengthy story to back
this up. When asked, as part of a memory test, to
remember the name of three objects which the examiner
listed ten minutes earlier, a person with Korsakoff’s may
list three entirely different objects and be completely
convincing in his or her certainty. In fact, one of the
hallmarks of Korsakoff’s is the person’s complete unawareness of the memory defect, and complete lack of
worry or concern when it is pointed out.

Diagnosis
Whenever someone has a possible diagnosis of
alcoholism, and then has the sudden onset of memory
difficulties, it is important to seriously consider the
diagnosis of Korsakoff’s syndrome. While there is no
specific laboratory test to diagnose Korsakoff’s syndrome in a patient, a careful exam of the individual’s
mental state should be rather revealing. Although the
patient’s ability to confabulate answers may be convincing, checking the patient’s retention of factual
2144

KEY TERMS
Amnesia—Inability to remember events or experiences. Memory loss. Includes: 1) Anterograde amnesia: inability to retain the memory of events occurring
after the time of the injury or disease which brought
about the amnesic state. 2) Retrograde amnesia:
inability to recall the memory of events which
occurred prior to the time of the injury or disease
which brought about the amnesic state.
Confabulation—An attempt to fill in memory gaps
by fabricating information or details.
Diencephalon—A part of the brain that binds the
mesencephalon to the cerebral hemispheres.
Considered by some as part of the brain stem.

information (asking, for example, for the name of the
current president of the United States), along with the
patient’s ability to learn new information (repeating a
series of numbers, or recalling the names of three
objects ten minutes after having been asked to memorize them) should point to the diagnosis. Certainly a
patient known to have just begun recovery from
Wernicke’s syndrome, who then begins displaying
memory difficulties, would be very likely to have
developed Korsakoff’s syndrome. A physical examination may also show signs of Wernicke’s syndrome,
such as peripheral neuropathy.

Treatment
Treatment of both Korsakoff’s and Wernicke’s
syndromes involves the immediate administration of
thiamine. In fact, any individual who is hospitalized
for any reason and who is suspected of being an alcoholic, should receive thiamine. The combined
Wernicke-Korsakoff syndrome has actually been precipitated in alcoholic patients hospitalized for other
medical illnesses, due to the administration of thiamine-free intravenous fluids (intravenous fluids are
those fluids containing vital sugars and salts which
are given to the patient through a needle inserted in a
vein). Also, the vitamin therapy may be impaired by
the feeding of carbohydrates prior to the giving of
thiamine; since carbohydrates cannot be metabolized
with thiamine.

Prognosis
Fifteen to twenty percent of all patients hospitalized for Wernicke’s syndrome will die of the disorder.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Kyphosis can be divided into three ages of acquisition—birth, old age, and the time in between.


Spinal birth defects can result in a fixed, exaggerated
curve. Vertebrae can be fused together, shaped
wrong, extraneous, or partially missing. Congenital
and hereditary defects in bone growth weaken
bone and result in exaggerated curves wherever
gravity or muscles pull on them. Dwarfism is such a
defect.



During life, several events can distort the spine.
Because the natural tendency of the thoracic spine
is to curve forward, any weakness of the supporting
structures will tend in that direction. A diseased
thoracic vertebra (a spine bone) will ordinarily
crumble its forward edge first, increasing the kyphotic curve. Conditions that can do this include cancer,
tuberculosis, Scheuermann’s disease, and certain
kinds of arthritis. Healthy vertebra will fracture
forward with rapid deceleration injuries, such as
in car crashes when the victim is not wearing a seat
belt.



Later in life, kyphosis is caused from osteoporosis,
bone weakness, and crumbling forward.

Prevention
Prevention depends on either maintaining a diet
with a sufficient intake of thiamine, or supplementing
an inadequate diet with vitamin preparations.
Certainly, one of the most important forms of prevention involves treating the underlying alcohol addiction.
Resources
ORGANIZATIONS

National Institute on Alcoholism Abuse and Alcoholism.
6000 Executive Boulevard, Willco Building, Bethesda,
Maryland 20892-7003. <http://www.niaaa.nih.gov>.

Rosalyn Carson-DeWitt, MD

KUB see Kidney, ureter, and bladder x-ray
study

The stress caused by kyphosis produces such
symptoms as an increase in musculoskeletal pains,
tension headaches, back aches, and joint pains.

Diagnosis
A quick look at the back will usually identify
kyphosis. X rays of the spine will confirm the diagnosis and identify its cause.

Kuru see Creutzfeldt-Jakob disease
Kwashiorkor see Protein-energy
malnutrition

Kyphosis
Definition
Kyphosis is the extreme curvature of the upper
back also known as a hunchback.

Description
The upper back bone (thoracic region), is normally curved forward. If the curve exceeds 508 it is
considered abnormal (kyphotic).
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Congenital defects have to be repaired surgically.
The procedures are delicate, complicated, and
lengthy. Often orthopedic hardware must be placed
to stabilize the back bone. At other times, a device
called a Milwaukee brace can hold the back in place
from the outside. Fitting Milwaukee braces comfortably is difficult because they tend to rub and cause
sores.
Kyphosis acquired during the younger years
requires treatment directed at the cause, such as medications for tuberculosis. Surgical reconstruction or
bracing may also be necessary.
Kyphosis induced by osteoporosis is generally
not treated except to prevent further bone
softening.
2145

Kyphosis

Although the degree of ataxia nearly always improves
with treatment, half of those who survive will continue
to have some permanent difficulty walking. The
paralysis of the eye muscles almost always resolves
completely with thiamine treatment. Recovery from
Wernicke’s begins to occur rapidly after thiamine is
given. Improvement in the symptoms of Korsakoff’s
syndrome, however, can take months and months of
thiamine replacement. Furthermore, patients who
develop Korsakoff’s syndrome are almost universally
memory-impaired for the rest of their lives. Even with
thiamine treatment, the memory deficits tend to be
irreversible, with less than 20% of patients even
approaching recovery. The development of
Korsakoff’s syndrome often results in an individual
requiring a supervised living situation.

Kyphosis

KEY TERMS
Congenital—Present at birth.
Dwarfism—A congenital disease of bone growth
that results in short stature and weak bones.
Orthopedic—Refers to surgery on the supporting
structures of the body–bones, joints, ligaments,
muscles.
Osteoporosis—A weakening of bones due to calcium loss that affects post-menopausal women.
Scheuermann’s disease—Juvenile kyphosis due to
damaged bone in the spinal vertebrae.

Prevention
Preventing osteoporosis is within the grasp of modern medicine. Menopausal women must start early with
estrogen replacement, calcium supplementation, and
appropriate exercise. The treatment must continue
through the remainder of life. Evidence suggests that a
high calcium intake even during younger years delays
the onset of symptomatic osteoporosis. Dairy products
are the major dietary sources of calcium.
Resources
ORGANIZATIONS
This patient’s spine shows excessive backward curvature at
the level of the upper chest. (Custom Medical Stock Photo.
Reproduced by permission.)

Prognosis
Congenital kyphosis may be alleviated to some
extent by surgery and bracing. Kyphosis occurring
later in life may worsen over time.

2146

Arthritis Foundation.1300 W. Peachtree St., Atlanta, GA
30309. (800) 283-7800. <http://www.arthritis.org>.
National Osteoporosis Foundation. 1150 17th St., Suite 500
NW, Washington, DC 20036-4603. (800) 223-9994.
<http://www.nof.org>.
Osteoporosis and Related Bone Diseases-National Resource
Center. 1150 17th S. NW, Ste. 500, Washington, DC
20036. (800) 624-2663.

J. Ricker Polsdorfer, MD

GALE ENCYCLOPEDIA OF MEDICINE

L
Labor and delivery see Childbirth
Labor induction see Induction of labor

Labyrinthitis
Definition
Labyrinthitis is an inflammation of the inner ear
that is often a complication of otitis media. It is caused
by the spread of bacterial or viral infections from the
head or respiratory tract into the inner ear.

Description
Labyrinthitis is characterized by dizziness or feelings of motion sickness caused by disturbance of the
sense of balance.

Causes and symptoms
Causes
The disease agents that cause labyrinthitis may
reach the inner ear by one of three routes:


Bacteria may be carried from the middle ear or the
membranes that cover the brain.



The viruses that cause mumps, measles, influenza, and
colds may reach the inner ear following an upper
respiratory infection.



The rubella virus can cause labyrinthitis in infants
prior to birth.
Labyrinthitis can also be caused by toxic drugs.
Symptoms

The primary symptoms of labyrinthitis are vertigo
(dizziness), accompanied by hearing loss and a
GALE ENCYCLOPEDIA OF MEDICINE

sensation of ringing in the ears called tinnitus.
Vertigo occurs because the inner ear controls the
sense of balance as well as hearing. Some patients
also experience nausea and vomiting and spontaneous
eye movements in the direction of the unaffected ear.
Bacterial labyrinthitis may produce a discharge from
the infected ear.

Diagnosis
The diagnosis of labyrinthitis is based on a combination of the patient’s symptoms and history–especially a history of a recent upper respiratory infection.
The doctor will test the patient’s hearing, and order a
laboratory culture to identify the organism if the
patient has a discharge.
If there is no history of a recent infection, the
doctor will order extra tests in order to exclude injuries
to the brain or Meniere’s disease.

Treatment
Medication
Patients with labyrinthitis are given antibiotics,
either by mouth or intravenously to clear up the infection. They may also be given meclizine (Antivert,
Bonine) for vertigo and nausea.
Surgery
Some patients require surgery to drain the inner
and middle ear.
Supportive care
Patients with labyrinthitis should rest in bed for
three to five days until the acute dizziness subsides.
Patients who are dehydrated by repeated vomiting may
need intravenous fluid replacement. In addition,
patients are advised to avoid driving or similar
2147

Laceration repair

KEY TERMS
Labyrinth—The bony cavity of the inner ear.
Meniere’s syndrome—A disease of the inner ear
marked by recurrent episodes of vertigo and roaring in the ears lasting several hours. Its cause is
unknown.
Otitis media—Inflammation of the middle ear. It
can lead to labyrinthitis.
Vertigo—A sensation of dizziness marked by the
feeling that one’s self or surroundings are spinning
or whirling.

activities for four to six weeks after the acute symptoms subside, because they may have occasional dizzy
spells during that period.

Prognosis
Most patients with labyrinthitis recover completely, although it often takes five to six weeks for the
vertigo to disappear completely and the patient’s hearing to return to normal. In a few cases the hearing loss
is permanent.

Prevention
The most effective preventive strategy includes
prompt treatment of middle ear infections, as well as
monitoring of patients with mumps, measles, influenza,
or colds for signs of dizziness or hearing problems.

Eleven sutures are necessary to close up the laceration on
this person’s forehead. (Custom Medical Stock Photo.
Reproduced by permission.)

Resources
BOOKS

Jackler, Robert K., and Michael J. Kaplan. ‘‘Ear, Nose, &
Throat.’’ In Current Medical Diagnosis and Treatment,
1998 edited by Stephen McPhee, et al., 37th ed.
Stamford: Appleton & Lange, 1997.

tissue may be lacerated, including subcutaneous fat,
tendon, muscle, or bone.

Purpose
A laceration should be repaired if it:

Rebecca J. Frey, PhD

Laceration repair



Continues to bleed after application of pressure for
ten to fifteen minutes



Is more than one-eighth to one-fourth inch deep



Exposes fat, muscle, tendon, or bone



Causes a change in function surrounding the area of
the laceration



Is dirty or has visible debris in it



Is located in an area where an unsightly scar is
undesirable.

Definition
A laceration is a wound caused by a sharp object
producing edges that may be jagged, dirty, or bleeding. Lacerations most often affect the skin, but any
2148

GALE ENCYCLOPEDIA OF MEDICINE

Laceration repair

KEY TERMS
Debridement—The act of removing any foreign
material and damaged or contaminated tissue
from a wound to expose surrounding healthy tissue.

Precautions

Improper wound closure

Lacerations are less likely to become infected if
they are repaired soon after they occur. Many physicians will not repair a laceration that is more than eight
hours old because the risk of infection is too great.

Description
Laceration repair mends a tear in the skin or other
tissue. The procedure is similar to repairing a tear in
clothing. Primary care physicians, emergency room physicians, and surgeons usually repair lacerations. The four
goals of laceration repair are to stop bleeding, prevent
infection, preserve function, and restore appearance.
Insurance companies do pay for the procedure. Cost
depends upon the severity and size of the laceration.
Before repairing the laceration, the physician
thoroughly examines the wound and the underlying
tendons or nerves. If nerves or tendons have been
injured, a surgeon may be needed to complete the
repair. The laceration is cleaned by removing any
foreign material or debris. Removing foreign objects
from penetrating wounds can sometimes cause bleeding, so this type of wound must be cleaned very carefully. The wound is then irrigated with saline solution
and a disinfectant. The disinfecting agent may be mild
soap or a commercial preparation. An antibacterial
agent may be applied.
Once the wound has been cleansed, the physician
anesthetizes the area of the repair by injecting a local
anesthetic. The physician may trim edges that are
jagged or extremely uneven. Tissue that is too
damaged to heal must be removed (debridement) to
prevent infection. If the laceration is deep, several
absorbable stitches (sutures) are placed in the tissue
under the skin to help bring the tissue layers together.
Suturing also helps eliminate any pockets where tissue
fluid or blood can accumulate. The skin wound is
closed with sutures. Suture material used on the surface of a wound is usually non-absorbable and will
have to be removed later. A light dressing or an adhesive bandage is applied for 24-48 hours. In areas where
a dressing is not feasible, an antibiotic ointment can be
applied. If the laceration is the result of a human or
GALE ENCYCLOPEDIA OF MEDICINE

Proper wound closure
A laceration is a traumatic break in the skin caused by a sharp
object producing edges that may be jagged, dirty, or bleeding. The underlying tissue may also be severed. In such
instances, the physician may place absorbable sutures in
the tissue to help bring the edges together before the skin is
sutured close. (Illustration by Electronic Illustrators Group.)

animal bite, if it is very dirty, or if the patient has a
medical condition that alters wound healing, oral antibiotics may be prescribed.

Aftercare
The laceration is kept clean and dry for at least
24 hours after the repair. Light bathing is generally permitted after 24 hours if the wound is not soaked. The
physician will provide directions for any special wound
care. Sutures are removed 3-14 days after the repair is
completed. Timing of suture removal depends on the
location of the laceration and physician preference.
The repair should be observed frequently for signs
of infection, which include redness, swelling, tenderness, drainage from the wound, red streaks in the skin
surrounding the repair, chills, or fever. If any of these
occur, the physician should be contacted immediately.

Risks
The most common complication of any laceration
repair is infection. Risk of infection can be minimized
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Lacrimal duct obstruction

by cleansing the wound thoroughly. Wounds from bites
or dirty objects or wounds that have a large amount of
dirt in them are most likely to become infected.
All lacerations will heal with a scar. Wounds that
are repaired with sutures are less likely to develop scars
that are unsightly, but no one can predict how wounds
will heal and who will develop unsightly scars. Plastic
surgery can improve the appearance of many scars.
Resources
OTHER

‘‘Caring for Cuts and Scrapes at Home.’’ Mayo Clinic
Online. <http://www.mayohealth.org/mayo/9611/
htm/cuts_sb.htm>.
‘‘Laceration Repair.’’ ThriveOnline. <http://
thriveonline.oxygen.com>.

Mary Jeanne Krob, MD, FACS

Lacerations see Wounds

Lacrimal duct obstruction
Definition
A lacrimal duct obstruction is blockage of the tear
duct, the thin channel that normally drains tears from
the surface of the eye.

Description
The lacrimal glands, located above each eyeball,
produce tears. The tears flow over the eye, then drain
through the nasolacrimal ducts. A tiny hole at the
inner edge of each eyelid marks the opening of the
ducts, which lead to the lacrimal sacs located on the
side of the nose. The tears pass from the sacs into the
nasolacrimal ducts and then into the nose.
When a tearduct becomes obstructed, tears may spill
over the eyelids and run down the face. Stagnant
tears within the system can become infected, leading to
recurrent red eyes and infections. Excessive tearing can
also producesecondary skin changes on the lower eyelids.

Causes and symptoms
An obstructed lacrimal tear duct can result in
inflammation and infection of the lacrimal sac. The
area beneath the eyes next to the nose can become red,
inflamed, and sensitive to the touch. The area usually
2150

is swollen, and there may be a mucous discharge from
the opening of the nasal corner of the eye. Common
complaints include itching, irritation, burning, redness, foreign body sensation, and tearing.
Children frequently have a congenital lacrimal
duct obstruction. Six to ten percent of all children
are born before their tear ducts are open.
In adults, a common cause of lacrimal duct
obstruction is involution, which is progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. Other causes
include eyelid disorders, infections by bacteria, viruses,
fungi, and parasites, inflammations, the use of eye
drops or excessive nasal spray, systemic chemotherapy,
trauma from previous surgeries, injury to the bone at
the side of the nose, foreign bodies, sinus disease, nasal
polyps, and malignant or benign tumors.

Diagnosis
If the primary symptom is excessive tearing, the first
step is for the health care professional to determine if the
overflow of tears is due to an increase in tear production
or a decrease in tear drainage. Causes of increased tear
production may include trichiasis, a disease in which the
eyelashes produce constant irritation, and eyelid malpositions and diseases. If abnormal tear production is
ruled out, then obstructions in tear drainage is the most
likely cause of the excessive tearing. Additional observations of swollen lacrimal sac area and purulent eye discharge indicate that there may be a lacrimal duct
infection present. To further define the diagnosis, the
lacrimal discharge may be cultured to determine possible infective agents, while various imaging techniques
may be used to detect the type of obstruction. Dye tracer
tests are also used to test for blockages.

Treatment
Lacrimal duct obstructions in children often
resolve spontaneously, with 95% showing resolution
before the child is one year old. Daily massaging of the
lacrimal sac may help open the blockage. A topical
antibiotic ointment may be applied if infection is present. If the blockage is not resolved after several weeks
to months of this therapy, a physician may attempt
forceful irrigation. Surgical probing to open up the
duct under general anesthesia is a last resort, after a
year or so of less invasive treatments.
In adults, conservative treatments are usually
recommended. The infected or inflamed area may be
massaged, with warm compresses applied to provide
relief and speed the healing process. The health care
GALE ENCYCLOPEDIA OF MEDICINE

Lacrimal duct—A short canal leading from a small
orifice at the medial angle of each eyelid to the
lacrimal sac.
Lacrimal gland—An almond-shaped gland that
secretes tears.
Lacrimal sac—The dilated upper end of the nasolacrimal duct in which the lacrimal ducts empty.
Nasolacrimal duct—A channel that transmits tears
from the lacrimal sac to the nose.
Purulent—Consisting of or containing pus
Tear—A drop of the clear, salty fluid secreted by
the lachrimal gland.
Trichiasis—A disease of the eye, in which the eyelashes, being turned in upon the eyeball, produce
constant irritation by the motion of the lids.

provider may also massage or irrigate the infected
area. Topical antibiotic ointments and oral antibiotics
may also be used reduce infection. The use of analgesics such as aspirin may be recommended to control
discomfort and reduce swelling. Severe cases may
require surgical intervention to prevent future recurrences. Surgical approaches include insertion of a
probe or catheter to remove an obstruction or creation
of an artificial duct to bypass the obstruction.

Prognosis
If more conservative approaches fail to clear the
obstruction, surgical procedures are available, with
success rates greater than 90%.

Prevention
In many cases, the cause of a lacrimal duct
obstruction is not known. However, in some cases,
lacrimal duct obstruction may be caused by smoking
and abuse of nasal sprays.
Resources
PERIODICALS

Camara, Jorge G., and Alfonso U. Bengzon. ‘‘Nasolacrimal
Duct Obstruction.’’ eMedicine Journal August 24, 2000.
<http://www.emedicine.com/OPH/topic465.htm>.

Judith Sims

Lacrimal sac infection see Dacryocystitis
GALE ENCYCLOPEDIA OF MEDICINE

Lactate dehydrogenase
isoenzymes test
Definition
The enzyme lactate dehydrogenase (also known as
lactic dehydrogenase, or LDH) is found in the cells of
almost all body tissues. The enzyme is especially concentrated in the heart, liver, red blood cells, kidneys,
muscles, brain, and lungs. The total LDH can be
further separated into five components or fractions
labeled by number: LDH-1, LDH-2, LDH-3, LDH-4,
and LDH-5. Each of these fractions, called isoenzymes, is used mainly by a different set of cells or
tissues in the body. For this reason, the relative
amounts of a particular isoenzyme of LDH in the
blood can provide valuable diagnostic information.

Purpose
The LDH isoenzymes test assists in differentiating
heart attack, anemia, lung injury, or liver disease from
other conditions that may cause the same symptoms
(differential diagnosis).

Precautions
Strenuous exercise may raise levels of total LDH,
specifically the isoenzymes LDH-1, LDH-2, and
LDH-5. Alcohol, anesthetics, aspirin, narcotics, procainamide, fluorides, and mithramycin may also raise
levels of LDH. Ascorbic acid (vitamin C) can lower
levels of LDH.

Description
LDH is found in the cells of almost all body
tissues. When certain conditions injure cells in tissues
containing LDH, it is released into the bloodstream.
Because LDH is so widely distributed throughout the
body, analysis of total LDH will not help make a
diagnosis of a particular disease. Because this enzyme
is actually composed of five different isoenzymes,
however, analysis of the different LDH isoenzyme
levels in the blood can help in the diagnosis of some
diseases.
The five LDH isoenzymes are: LDH-1, LDH-2,
LDH-3, LDH-4, and LDH-5. In general, each isoenzyme is used mostly by the cells in a specific tissue.
LDH-1 is found mainly in the heart. LDH-2 is
primarily associated with the system in the body
that defends against infection (reticuloendothelial
system). LDH-3 is found in the lungs and other
2151

Lactate dehydrogenase isoenzymes test

KEY TERMS

Lactate dehydrogenase isoenzymes test

tissues, LDH-4 in the kidney, placenta, and pancreas,
and LDH-5 in liver and striated (skeletal) muscle.
Normally, levels of LDH-2 are higher than those of
the other isoenzymes.

KEY TERMS
Differential diagnosis—Comparing and contrasting the signs, symptoms, and laboratory findings
of two or more diseases to determine which is
causing the patient’s condition.
Enzyme—A protein that regulates the rate of a chemical reaction in the body, increasing the speed at
which the change occurs.
Isoenzyme—One of a group of enzymes that bring
about the same reaction but are vary in their physical properties.

Certain diseases have classic patterns of elevated
LDH isoenzyme levels. For example, an LDH-1 level
higher than that of LDH-2 is indicative of a heart
attack or injury; elevations of LDH-2 and LDH-3
indicate lung injury or disease; elevations of LDH-4
and LDH-5 indicate liver or muscle disease or both.
A rise of all LDH isoenzymes at the same time is
diagnostic of injury to multiple organs. For example,
a heart attack with congestive heart failure may cause
symptoms of lung and liver congestion. Advanced
cancer and autoimmune diseases such as lupus can
also cause this pattern.
One of the most important diagnostic uses for the
LDH isoenzymes test is in the differential diagnosis
of myocardial infarction or heart attack. The total
LDH level rises within 24–48 hours after a heart
attack, peaks in two to three days, and returns to
normal in approximately five to ten days. This pattern is a useful tool for a delayed diagnosis of heart
attack. The LDH-1 isoenzyme level, however, is more
sensitive and specific than the total LDH. Normally,
the level of LDH-2 is higher than the level of LDH-1.
An LDH-1 level higher than that of LDH-2, a phenomenon known as ‘‘flipped LDH,’’ is strongly indicative of a heart attack. The flipped LDH usually
appears within 12–24 hours after a heart attack. In
about 80% of cases, flipped LDH is present within 48
hours of the incident. A normal LDH-1/LDH-2 ratio
is considered reliable evidence that a heart attack has
not occurred.
It should be noted that two conditions might
cause elevated LDH isoenzymes at the same time and
that one may confuse the other. For example, a patient
with pneumonia may also be having an acute heart
attack. In this instance, the LDH-1 level would rise
with the LDH-2 and LDH-3. Because of this complication, some laboratories measure only the LDH-1
and consider an elevated LDH level with LDH-1
higher than 40% to be diagnostic of heart damage.
LDH isoenzymes test is not used much anymore for
diagnosis of heart attack. Tests for the protein troponin, which is found in myocardial cells, have been
found to be more accurate.

Preparation
This test requires a blood sample. The patient
need not fast (nothing to eat or drink) before the test
unless requested to do so by the physician.
2152

Risks
Risks for this test are minimal. The patient may
experience slight bleeding from the blood-drawing
site, fainting or feeling lightheaded after the vein is
punctured (venipuncture), or an accumulation of
blood under the puncture site (hematoma).

Normal results
Reference values for normal levels of LDH isoenzymes vary from laboratory to laboratory but can
generally be found within the following ranges:


LDH-1: 17-27%



LDH-2: 27-37%



LDH-3: 18-25%



LDH-4: 8-16%



LDH-5: 6-16%.

Abnormal results
Increased levels of LDH-1 are seen in myocardial
infarction, red blood cell diseases like hemolytic anemia, kidney disease including kidney transplantation
rejection, and testicular tumors. Increased levels of
LDH-2 are found in lung diseases such as pneumonia
and congestive heart failure, as well as in lymphomas
and other tumors. Elevations of LDH-3 are significant
in lung disease and certain tumors. Elevations of
LDH-4 are greatly increased in pancreatitis. High
levels of LDH-5 are found in liver disease, intestinal
problems, and skeletal muscle disease and injury, such
as muscular dystrophy and recent muscular trauma.
Diffuse disease or injury (for example, collagen
disease, shock, low blood pressure) and advanced
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Lactate dehydrogenase test
Definition
Lactate dehydrogenase, also called lactic dehydrogenase, or LDH, is an enzyme found in the cells
of many body tissues, including the heart, liver, kidneys, skeletal muscle, brain, red blood cells, and lungs.
It is responsible for converting muscle lactic acid into
pyruvic acid, an essential step in producing cellular
energy.

Purpose
Lactic dehydrogenase is present in almost all body
tissues, so the LDH test is used to detect tissue alterations and as an aid in the diagnosis of heart attack,
anemia, and liver disease. Newer injury markers are
becoming more useful than LDH for heart attack
diagnosis.

Precautions
Because the LDH enzyme is so widely distributed
throughout the body, cellular damage causes an elevation of the total serum LDH. As a result, the diagnostic usefulness of this enzyme by itself is not as valuable
as determination of the five fractions that comprise the
LDH. These fractions are called isoenzymes and are
better indicators of disease than is the total LDH. The
fractions are LDH-1, LDH-2, LDH-3, LDH-4, and
LDH-5. A normal total LDH level does not mean that
individual isoenzyme levels should not be measured.
Individual isoenzyme ranges can help differentiate a
diagnosis.

Description
When disease or injury affects tissues containing
LDH, the cells release LDH into the bloodstream,
where it is identified in higher than normal levels.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Enzyme—A protein that regulates the rate of a chemical reaction in the body, increasing the speed at
which the change occurs.
Isoenzyme—One of a group of enzymes that catalyze the same reaction but are differentiated by
variations in physical properties.

For example, when a person has a heart attack, the
LDH level begins to rise about 12 hours after the
attack and usually returns to normal within 5-10
days. The LDH is also elevated in diseases of the
liver, in certain types of anemia, and in cases of excessive destruction of cells, as in fractures, trauma, muscle
damage, and shock.
Cancers can also elevate LDH level. Additionally,
some patients have chronically elevated LDH with no
identifiable cause and no apparent consequence.

Preparation
This test requires a blood sample. It is not necessary for the patient to fast (nothing to eat or drink)
before the test unless the physician requests it.

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or
feeling lightheaded after venipuncture, or hematoma
(blood accumulating under the puncture site).

Normal results
Reference ranges for total LDH vary from laboratory to laboratory. Normal values are also higher in
childhood. For adults, in most laboratories, the range
can be up to approximately 200 units/L, but is usually
found within 45-90 U/L.

Abnormal results
Due to the fact that many common disease processes cause elevations in the total LDH level, a breakdown of the five different isoenzymes that make up the
total LDH is often helpful for diagnosis. In certain
disorders, the total LDH may be within normal limits,
but individual isoenzyme elevations can indicate specific organ or tissue damage. For example, the LDH-2
fraction is normally greater than LDH-1 in the blood.
2153

Lactate dehydrogenase test

solid-tumor cancers cause significant elevations of all
LDH isoenzymes at the same time.

Lactation

After an acute heart attack, however, the LDH-1 rises
over the LDH-2 in what is known as a ‘‘flipped LDH.’’
Certain diagnoses can be assisted by determination of the total LDH. One example is infectious mononucleosis, in which the LDH is usually more elevated
than a liver enzyme called AST. Conversely, in cases of
viral hepatitis, the liver enzymes AST and ALT are
greatly increased over the LDH.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Lactation
Definition
Lactation is the medical term for yielding of milk
by the mammary glands which leads to breastfeeding.
Human milk contains the ideal amount of nutrients
for the infant, and provides important protection from
diseases through the mother’s natural defenses.

Description
Early in a woman’s pregnancy her milk-producing
glands begin to prepare for her baby’s arrival, and by
the sixth month of pregnancy the breasts are ready to
produce milk. Immediately after the baby is born, the
placenta is delivered. This causes a hormone in the
woman’s body (prolactin) to activate the milk-producing
glands. By the third to fifth day, the woman’s breasts
fill with milk.
Then, as the baby continues to suck each day,
nursing triggers the continuing production of milk.
The baby’s sucking stimulates nerve endings in the
nipple, which signal the mother’s pituitary gland to
release oxytocin, a hormone that causes the mammary
glands to release milk to the nursing baby. This is
called the ‘‘let-down reflex.’’ While the baby’s sucking
is the primary stimulus for this reflex, a baby’s cry,
thoughts of the baby, or the sound of running water
also may trigger the response. Frequent nursing will
lead to increased milk production.
Breast milk cannot be duplicated by commercial
baby food formulas, although both contain protein,
fat, and carbohydrates. In particular, breast milk
2154

changes to meet the specific needs of a baby. The
composition of breast milk changes as the baby
grows to meet the baby’s changing needs. Most important, breast milk contains substances called antibodies
from the mother that can protect the child against
illness and allergies. Antibodies are part of the
body’s natural defense system against infections and
other agents that can cause disease. Breast milk also
helps a baby’s own immune system mature faster. As a
result, breast-fed babies have less diarrhea and fewer
ear infections, rashes, allergies, and other medical problems than bottle-fed babies.
There are many other benefits to breast milk.
Because it is easily digested, babies do not get constipated. Breast-fed babies may have fewer speech impediments, and breastfeeding can improve cheekbone
development and jaw alignment.
Breastfeeding is also good for the mother. The act
of breastfeeding releases hormones that stimulate the
uterus to contract, helping it to return to normal size
after delivery and reducing the risk of bleeding. The
act of producing milk is thought to burn more calories,
helping the mother to lose excess weight gained during
pregnancy. However, research in 2004 disputed this
belief when body composition changes of lactation
and non-lactating women were compared at intervals
for six months postpartum. Breastfeeding may be
related to a lower risk of breast cancer, ovarian cancer,
or cervical cancer. This benefit is stronger the younger
a woman is when she breastfeeds; women who breastfeed before age 20 and nurse for at least six months
have a 50% drop in the risk for breast cancer.
In addition, breastfeeding does not involve any
formulas, bottles and nipples, or sterilizing equipment.
Breast milk is free, and saves money by eliminating the
need to buy formula, bottles, and nipples. Because
breast-fed babies are healthier, health care costs for
breast-fed infants are lower.
Procedure
Breastfeeding should begin as soon as possible
after birth, and should continue every two to three
hours. However, all babies are different; some need
to nurse almost constantly at first, while others can go
much longer between feedings. A baby should be fed
at least 8-12 times in 24 hours. Because breast milk is
easily digested, a baby may be hungry again as soon as
one and one-half hours after the last meal.
Mothers should wear comfortable, loose, frontopening clothes and a good nursing bra. Mothers
should find a comfortable chair with lots of pillows,
supporting the arm and back. Feet should rest on a
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Bromocriptine —A drug used to treat Parkinson’s
disease that can decrease a woman’s milk supply.
Ergotamine—A drug used to prevent or treat
migraine headaches. This can cause vomiting, diarrhea, and convulsions in infants.

Some babies have no trouble breastfeeding, while
others may need some assistance. Once the baby begins
to suck, the mother should make sure that the entire
dark area around the nipple is in the baby’s mouth. This
will help stimulate milk flow, allowing the baby to get
enough milk. It will also prevent nipple soreness.
Breastfeeding mothers will usually offer the baby
both breasts at each feeding. Breastfeeding takes
about 15-20 minutes on each side. After stopping the
feeding on one side, the mother should burp the baby
before beginning the feeding on the other breast. If the
baby falls asleep at the breast, the next feeding should
begin with the breast that was not nursed.
Mothers can tell if the baby is getting enough milk
by checking diapers; a baby who is wetting between
four to six disposable diapers (six to eight cloth) and
who has three or four bowel movements in 24 hours is
getting enough milk.
Nursing problems
New mothers may experience nursing problems,
including:

Lithium—A drug used to treat manic depression
(bipolar disorder) that can be transmitted in breast
milk.
Methotrexate—An anticancer drug also used to
treat arthritis that can suppress an infant’s immune
system when taken by a nursing mother.

Many medications have not been tested in nursing
women, so it is not known if these drugs can affect a
breast-fed child. A nursing woman should always
check with her doctor before taking any medications,
including over-the-counter drugs.
These drugs are not safe to take while nursing:


Radioactive drugs for some diagnostic tests



Chemotherapy drugs for cancer



Bromocriptine



Ergotamine

Engorged breasts. Breasts that are too full can prevent the baby from sucking. Expressing milk manually or with a breast pump can help.



Lithium



Methotrexate



Sore nipples. In the early weeks nipples may become
sore; a nipple shield can ease discomfort.



Street drugs
amphetamines)



Infection. Soreness and inflammation on the breast
surface or a fever in the mother, may be an indication
of breast infection. Antibiotics and continued nursing
on the affected side may solve the problem.



Tobacco.



Prognosis
There are no rules about when to stop breastfeeding. A baby needs breast milk for at least the first year
of life; as long as a baby eats age-appropriate solid
food, the mother may nurse for several years.

Prevention
Most common illnesses can not be transmitted via
breast milk. However, some viruses, including HIV
(the virus that causes AIDS) can be passed in breast
milk; for this reason, women who are HIV-positive
should not breastfeed.
GALE ENCYCLOPEDIA OF MEDICINE

(including

marijuana,

heroin,

Resources
PERIODICALS

Wosje, Karen S., and Heidi J. Kalkwarf. ‘‘Lactation,
Weaning, and Calcium Supplementation: Effects on
Body Composition in Postpartum Women.’’ American
Journal of Clinical Nutrition August 2004: 676.
ORGANIZATIONS

International Lactation Consultants Assoc. 201 Brown
Ave., Evanston, IL 60202. (708) 260-8874.
La Leche League International. 1400 North Meacham Rd.,
Schaumburg, IL 60173. (800) LA-LECHE.
National Alliance for Breastfeeding Advocacy. 254 Conant
Rd., Weston, MA 02193. (617) 893-3553.

Carol A. Turkington
Teresa G. Odle
2155

Lactation

low footstool, with knees raised slightly. The baby
should be level with the breast. The new mother may
have to experiment with different ways of holding the
baby before finding one that is comfortable for both
the mother and baby.

Lactic acid test

KEY TERMS

Lactic acid test
Definition
Lactic acid is an acid produced by cells during
chemical processes in the body that do not require
oxygen (anaerobic metabolism). Anaerobic metabolism occurs only when too little oxygen is present for
the more usual aerobic metabolism (oxygen requiring). Lactic acid is a contributing factor in muscle
cramps. It is also produced in tissues when conditions
such as heart attack or shock reduce the blood supply
responsible for carrying oxygen. Normally, lactic acid
is removed from the blood by the liver. When an excess
of lactic acid accumulates for any reason, the result is a
condition called lactic acidosis.

Purpose
The lactic acid test is used as an indirect assessment of the oxygen level in tissues and to determine the
cause and course of lactic acidosis.

Precautions
During blood collection, the patient should be
instructed to relax the hand. Clenching and unclenching the fist will cause a build-up of potassium and
lactic acid from the hand muscles that will falsely
elevate the levels.

Acidosis—A disturbance of the balance of acid to
base in the body causing an accumulation of acid
or loss of alkali (base). There are two types of
acidosis: metabolic and respiratory. One of the
most common causes of metabolic acidosis is an
overdose of aspirin. Respiratory acidosis is caused
by impaired breathing caused by conditions such
as severe chronic bronchitis, bronchial asthma, or
airway obstruction.

levels are low, pyruvate converts to lactic acid; when
oxygen levels are adequate, lactic acid converts to
pyruvate. When the liver fails to metabolize lactose
sufficiently or when too much pyruvate converts to
lactate, lactic acidosis occurs. Measurement of blood
lactate levels is recommended for all patients with
symptoms of lactic acidosis. Testing is generally indicated if the blood pH level falls below 7.25-7.35.
Because of the close relationship between pyruvate and lactic acid, comparison of blood levels of the
two substances can provide reliable information about
tissue oxidation. However, pyruvate measurement is
technically difficult and seldom performed. Lactic acid
is measured more often, in either venous or arterial
blood samples.

Description
The degree of acidity is an important chemical
property of blood and other body fluids. Acidity is
expressed on a pH scale where 7.0 is neutral, above 7.0
is basic (alkaline), and below 7.0 is acidic. A strong
acid has a very low pH (near 1.0). A strong base has a
very high pH (near 14.0). Blood is normally slightly
alkaline or basic. It has a pH range of 7.35-7.45. The
balance of acid to base in blood is precisely controlled.
Even a minor deviation from the normal range can
severely affect many organs.
Lactic acid (present in the blood as lactate ion) is a
product of the breakdown of glucose to generate
energy. It is found primarily in muscle cells and red
blood cells. The lactate ion concentration in the blood
depends on the rates of energy production and metabolism. Levels may increase significantly during
exercise.
Together, lactic acid and another chemical (pyruvate) form a reversible reaction regulated by the
oxygen supply to the blood and tissues. When oxygen
2156

Preparation
This test requires a blood sample. The patient
should have nothing to eat or drink (fasting) from
midnight the night before the test. Because lactic acid
is produced by exertion, the patient should rest for at
least one hour before the test.

Risks
Risks for this test are minimal. The patient may
experience slight bleeding from the blood-drawing
site, fainting or feeling lightheaded after puncture of
the vein (venipuncture), or an accumulation of blood
under the puncture site (hematoma).

Normal results
Reference values vary from laboratory to laboratory but can be found within the following ranges:


Venous blood: 4.5-19.8 mg/dL



Arterial blood: 4.5-14.4 mg/dL.
GALE ENCYCLOPEDIA OF MEDICINE

High blood lactate levels, together with decreased
oxygen in tissues, may be caused by strenuous muscle
exercise, shock, hemorrhage, severe infection in the
blood stream, heart attack, or cardiac arrest. When
tissue oxygenation is low for no apparent reason,
increased lactate levels may be caused by systemic
disorders like diabetes, leukemia, liver disease, or kidney failure. Defects in enzymes may also be responsible, as in glycogen storage disease (von Gierke’s
disease). Lactate is also increased in certain instances
of intestinal obstruction.
Lactic acidosis can be caused by taking large doses
of acetaminophen and alcohol and by intravenous
infusion of epinephrine, glucagon, fructose, or sorbitol. Antifreeze poisoning can also cause lactic acidosis.
In rare instances, a diabetic medication, metformin
(Glucophage), causes lactic acidosis. People with
weak kidneys should not take metformin.
Resources
BOOKS

Pagana, Kathleen Deska, and Timothy James Pagana.
Mosby’s Manual of Diagnostic and Laboratory Tests.
St. Louis: Mosby, Inc., 1998.

Paul A. Johnson, Ed.M.

Lactic acidosis see Metabolic acidosis
Lactogen test see Prolactin test
Lactogenic hormone test see Prolactin test

Lactose intolerance
Definition
Lactose intolerance refers to the inability of the
body to digest lactose.

Description
Lactose is the form of sugar present in milk. The
enzyme lactase, which is normally produced by cells
lining the small intestine, breaks down lactose into
substances that can be absorbed into the bloodstream.
When dairy products are ingested, the lactose reaches
the digestive system and is broken down by lactase
into the simpler sugars glucose and galactose. The
liver changes the galactose into glucose, which then
GALE ENCYCLOPEDIA OF MEDICINE

enters the bloodstream and raises the blood glucose
level. Lactose intolerance occurs when, due to a deficiency of lactase, lactose is not completely broken
down and the glucose level does not rise. While not
usually dangerous, lactose intolerance can cause
severe discomfort.
From 30 to 50 million Americans suffer from the
symptoms of lactose intolerance, but not everyone
who is deficient in lactase experiences symptoms.
Experts believe that 75% of the adult population
worldwide does not produce enough lactase and is at
risk for some or all of the symptoms of lactose
intolerance.

Causes and symptoms
Lactose intolerance can be caused by some diseases of the digestive system and by injuries to the
small intestine that result in a decreased production
of lactase. While rare, some children are also born
unable to produce the enzyme. For many, however,
lactase deficiency develops naturally because, after
about two years of age, the body produces less lactase.
Symptoms include nausea, cramps, diarrhea,
bloating and gas. The symptoms usually occur
between 30 minutes to two hours after eating or drinking lactose-containing foods.

Diagnosis
Usually, health care professionals measure the
absorption of lactose in the digestive system by using
the lactose tolerance test, hydrogen breath test or stool
acidity test. Each of these can be performed outpatient, through a hospital, clinic or doctor’s office.
People taking the lactose tolerance test must fast
before being tested. They then drink a lactose-containing liquid for the test and medical personnel take blood
samples during the next two hours to measure the
patient’s blood glucose level. The blood glucose level,
or blood sugar level, indicates how well the body is
digesting the lactose. A diagnosis of lactose intolerance
is confirmed when blood glucose level does not rise.
This test is not administered to infants and very young
children because they are more prone to dehydration,
which can result from diarrhea from the liquid.
Health care professionals measure the amount of
hydrogen in the breath using the hydrogen breath test.
Hydrogen is usually detected only in small amounts in
the breath. However when undigested lactose found in
the colon is fermented by bacteria, hydrogen in the
breath is produced in greater quantities. The hydrogen
is exhaled after being absorbed from the intestines and
2157

Lactose intolerance

Abnormal results

Lactose intolerance

carried through the bloodstream to the lungs. The
hydrogen breath test involves having the patient
drink a lactose-containing beverage. Health care professionals monitor the breath at regular intervals to see
if the hydrogen levels rise, which indicates improper
lactose digestion. People taking the test who have had
certain foods, medications or cigarettes before the test
may get inaccurate results. While the test is available
to children and adults, newborns and young children
should not have it because of the risk of dehydration
from drinking the beverage that can cause diarrhea in
those who are lactose intolerant.
A stool acidity test measures the amount of acid in
the stool. This is a safe test for newborns and young
children. The test detects lactic acid and other shortchain fatty acids from undigested lactose fermented by
bacteria in the colon. Glucose might also be in the
stool sample, resulting form unabsorbed lactose in
the colon.

Treatment
Pediatricians might recommend that parents of
newborns and very young children who are suspected
of having lactose intolerance simply change from
cow’s milk to a soya formula. Since there is no treatment that can improve the body’s ability to produce
lactase, lactose deficiency treatments instead, are
focused on controlling the diet.
Most people affected by lactose intolerance do
well if they limit their intake of lactose foods and
drinks. People differ in the amounts they can handle
before experiencing symptoms. Some have to stop
lactose completely. People who are sensitive after
ingesting small amounts of lactose can take lactase
enzymes, which are available without a prescription.
Using the liquid form, people can add a few drops in
their milk, put the milk in the refrigerator and drink it
after 24 hours, when the lactase enzymes have worked
to reduce the lactose content by 70%. If the milk is
heated first and double the amount of lactase liquid is
added, the milk will be 90 percent lactose free.
Recently, researchers have developed a chewable lactase enzyme tablet. By taking three to six tablets just
before eating, the tablets help people digest lactosecontaining solid foods. Supermarkets also carry lactose-reduced mild and other products, which contain
the needed nutrients found in the regular products but
without the lactose.
Foods that contain lactose are milk, low-fat milk,
skim milk, chocolate milk, buttermilk, sweetened condensed milk, dried whole milk, instant nonfat dry
milk, low-fat yogurts, frozen yogurts ice cream, ice
2158

KEY TERMS
Galactose—Simple sugar derived from milk sugar.
Glucose—A simple sugar and the chief energy
source in the body.
Lactase enzyme—The enzyme produced by cells
that line the small intestine which allows the body
to break down lactose.
Lactose—The primary sugar in milk.

milk, sherbet, cheese, cottage cheese, low-fat cottage
cheese, cream and butter. Other foods that may contain hidden lactose are: nondairy creamers, powdered
artificial sweeteners, foods containing milk power or
nonfat milk solids, bread, cake, margarine, creamed
soups, pancakes, waffles, processed breakfast cereals,
salad dressings, lunch meats, puddings, custards, confections and some meat products.

Prognosis
Lactose intolerance is easy to manage. People of
all ages however, especially children, have to replace
the calcium lost by cutting back on milk products by
taking supplements and eating calcium-rich foods,
such as broccoli, kale, canned salmon with bones,
calcium-fortified foods and tofu. Many people who
suffer with lactose intolerance will be able to continue
eating some milk products. The condition is not considered dangerous.

Prevention
Often, lactose intolerance is a natural occurrence
that cannot be avoided. However, people can prevent
symptoms by managing the condition with diet and
lactase supplements.
Resources
ORGANIZATIONS

American Dietetic Association. (800) 366-1655. <http://
www.eatright.org/nfs/nfs43.html>.
OTHER

‘‘Lactose Intolerance.’’ Onebody.com. <http://
www.onebody.com>.

Lisette Hilton

Lambliasis see Giardiasis
Laminectomy see Disk removal
GALE ENCYCLOPEDIA OF MEDICINE

Laparoscopic cholecystectomy see
Cholecystectomy

Laparoscopy
Definition
Laparoscopy is a type of surgical procedure in
which a small incision is made, usually in the navel,
through which a viewing tube (laparoscope) is inserted.
The viewing tube has a small camera on the eyepiece.
This allows the doctor to examine the abdominal and
pelvic organs on a video monitor connected to the tube.
Other small incisions can be made to insert instruments
to perform procedures. Laparoscopy can be done to
diagnose conditions or to perform certain types of
operations. It is less invasive than regular open abdominal surgery (laparotomy).

Diagnostic procedure
As a diagnostic procedure, laparoscopy is useful
in taking biopsies of abdominal or pelvic growths, as
well as lymph nodes. It allows the doctor to examine
the abdominal area, including the female organs,
appendix, gallbladder, stomach, and the liver.
Laparoscopy is used to determine the cause of
pelvic pain or gynecological symptoms that cannot
be confirmed by a physical exam or ultrasound. For
example, ovarian cysts, endometriosis, ectopic pregnancy, or blocked fallopian tubes can be diagnosed
using this procedure. It is an important tool when
trying to determine the cause of infertility.
Operative procedure
While laparoscopic surgery to completely remove
cancerous tumors, surrounding tissues, and lymph
nodes is used on a limited basis, this type of operation
is widely used in noncancerous conditions that once
required open surgery. These conditions include:


Tubal ligation. In this procedure, the fallopian tubes
are sealed or cut to prevent subsequent pregnancies.



Ectopic pregnancy. If a fertilized egg becomes
embedded outside the uterus, usually in the fallopian
tube, an operation must be performed to remove the
developing embryo. This often can be done with
laparoscopy.



Endometriosis. This is a condition in which tissue
from inside the uterus is found outside the uterus in
other parts of (or on organs within) the pelvic cavity.
This can cause cysts to form. Endometriosis is diagnosed with laparoscopy, and in some cases the cysts
and other tissue can be removed during laparoscopy.



Hysterectomy. This procedure to remove the uterus
can, in some cases, be performed using laparoscopy.
The uterus is cut away with the aid of the laparoscopic instruments and then the uterus is removed
through the vagina.



Ovarian masses. Tumors or cysts in the ovaries can
be removed using laparoscopy.



Appendectomy. This surgery to remove an inflamed
appendix required open surgery in the past. It is now
routinely performed with laparoscopy.



Cholecystectomy. Like appendectomy, this procedure to remove the gall bladder used to require
open surgery. Now it can be performed with laparoscopy, in some cases.

Purpose
Since the late 1980s, laparoscopy has been a popular diagnostic and treatment tool. The technique
dates back to 1901, when it was reportedly first used
in a gynecologic procedure performed in Russia. In
fact, gynecologists were the first to use laparoscopy to
diagnose and treat conditions relating to the female
reproductive organs: uterus, fallopian tubes, and
ovaries.
Laparoscopy was first used with cancer patients in
1973. In these first cases, the procedure was used to
observe and biopsy the liver. Laparoscopy plays a role
in the diagnosis, staging, and treatment for a variety of
cancers.
As of 2001, the use of laparoscopy to completely
remove cancerous growths and surrounding tissues (in
place of open surgery) is controversial. The procedure
is being studied to determine if it is as effective as open
surgery in complex operations. Laparoscopy is also
being investigated as a screening tool for ovarian
cancer.
Laparoscopy is widely used in procedures for
noncancerous conditions that in the past required
open surgery, such as removal of the appendix
(appendectomy) and gallbladder removal (cholecystectomy).
GALE ENCYCLOPEDIA OF MEDICINE

In contrast to open abdominal surgery, laparoscopy usually involves less pain, less risk, less scarring,
and faster recovery. Because laparoscopy is so much
2159

Laparoscopy

Language disturbance see Aphasia

Laparoscopy

less invasive than traditional abdominal surgery,
patients can leave the hospital sooner.
Cancer staging
Laparoscopy can be used in determining the
spread of certain cancers. Sometimes it is combined
with ultrasound. Although laparoscopy is a useful
staging tool, its use depends on a variety of factors,
which are considered for each patient. Types of cancers where laparoscopy may be used to determine the
spread of the disease include:




Liver cancer. Laparoscopy is an important tool for
determining if cancer is present in the liver. When a
patient has non-liver cancer, the liver is often
checked to see if the cancer has spread there.
Laparoscopy can identify up to 90% of malignant
lesions that have spread to that organ from a cancer
located elsewhere in the body. While computerized
tomography (CT) can find cancerous lesions that
are 0.4 in (10 mil) in size, laparoscopy is capable
of locating lesions that are as small as 0.04 in
(1 millimeter).
Pancreatic cancer. Laparoscopy has been used to
evaluate pancreatic cancer for years. In fact, the
first reported use of laparoscopy in the United
States was in a case involving pancreatic cancer.



Esophageal and stomach cancers. Laparoscopy has
been found to be more effective than magnetic resonance imaging (MRI) or computerized tomography
(CT) in diagnosing the spread of cancer from these
organs.



Hodgkin’s disease. Some patients with Hodgkin’s
disease have surgical procedures to evaluate lymph
nodes for cancer. Laparoscopy is sometimes selected
over laparotomy for this procedure. In addition, the
spleen may be removed in patients with Hodgkin’s
disease. Laparoscopy is the standard surgical technique for this procedure, which is called a splenectomy.



Prostate cancer. Patients with prostate cancer may
have the nearby lymph nodes examined.
Laparoscopy is an important tool in this procedure.
Cancer treatment

Laparoscopy is sometimes used as part of a palliative cancer treatment. This type of treatment is not a
cure, but can often lessen the symptoms. An example is
the feeding tube, which cancer patients may have if
they are unable to take in food by mouth. The feeding
tube provides nutrition directly into the stomach.
Inserting the tube with a laparoscopy saves the patient
the ordeal of open surgery.
2160

This surgeon is performing a laparoscopic procedure on a
patient. (Photo Researchers, Inc. Reproduced by permission.)

Precautions
As with any surgury, patients should notify their
physician of any medications they are taking
(prescription, over-the-counter, or herbal) and of any
allergies. Precautions vary due to the several different
purposes for laparoscopy. Patients should expect to
rest for several days after the procedure, and should
set up a comfortable environment in their home (with
items such as pain medication, heating pads, feminine
products, comfortable clothing, and food readily
accessible) prior to surgery.

Description
Laparoscopy is a surgical procedure that is done
in the hospital under anesthesia. For diagnosis and
biopsy, local anesthesia is sometimes used. In operative procedures, such as abdominal surgery, general
anesthesia is required. Before starting the procedure, a
catheter is inserted through the urethra to empty the
bladder, and the skin of the abdomen is cleaned.
After the patient is anesthetized, a hollow needle is
inserted into the abdomen in or near the navel, and
carbon dioxide gas is pumped through the needle to
expand the abdomen. This allows the surgeon a better
view of the internal organs. The laparoscope is then
inserted through this incision to look at the internal
organs. The image from the camera attached to the
end of the laparoscope is seen on a video monitor.
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
Patients should not eat or drink after midnight on
the night before the procedure.

Aftercare
After the operation, nurses will check the vital
signs of patients who had general anesthesia. If there
are no complications, the patient may leave the hospital within four to eight hours. (Traditional abdominal
surgery requires a hospital stay of several days).
There may be some slight pain or throbbing at the
incision sites in the first day or so after the procedure.
The gas that is used to expand the abdomen may cause
discomfort under the ribs or in the shoulder for a few
days. Depending on the reason for the laparoscopy in
gynecological procedures, some women may experience some vaginal bleeding. Many patients can return
to work within a week of surgery and most are back to
work within two weeks.

Risks
Laparoscopy is a relatively safe procedure, especially if the physician is experienced in the technique.
The risk of complication is approximately 1%.
The procedure carries a slight risk of puncturing a
blood vessel or organ, which could cause blood to seep
into the abdominal cavity. Puncturing the intestines
could allow intestinal contents to seep into the cavity.
These are serious complications and major surgery
may be required to correct the problem. For operative
procedures, there is the possibility that it may become
apparent that open surgery is required. Serious complications occur at a rate of only 0.2%.

KEY TERMS
Biopsy—Microscopic evaluation of a tissue sample. The tissue is closely examined for the presence
of abnormal cells.
Cancer staging—Determining the course and
spread of cancer.
Cyst—An abnormal lump or swelling that is filled
with fluid or other material.
Palliative treatment—A type treatment that does
not provide a cure, but eases the symptoms.
Tumor—A growth of tissue, benign or malignant,
often referred to as a mass.

Normal results
In diagnostic procedures, normal results would
indicate no abnormalities or disease of the organs or
lymph nodes that were examined.

Abnormal results
A diagnostic laparoscopy may reveal cancerous or
benign masses or lesions. Abnormal findings include
tumors or cysts, infections (such as pelvic inflammatory disease), cirrhosis, endometriosis, fibroid tumors,
or an accumulation of fluid in the cavity. If a doctor is
checking for the spread of cancer, the presence of
malignant lesions in areas other than the original site
of malignancy is an abnormal finding.
Resources
BOOKS



hemorrhage

Kurtz, Robert C., and Robert J. Ginsberg. ‘‘Cancer Diagnosis:
Endoscopy.’’ In Cancer: Principles & Practice of
Oncology, edited by Vincent T. DeVita, Jr. Philadelphia:
Lippincott, Williams & Wilkins, 2001, pp. 725-27.
Lefor, Alan T. ‘‘Specialized Techniques in Cancer
Management.’’ In Cancer: Principles & Practice of
Oncology, edited by Vincent T. DeVita Jr., et al., 6th ed.
Philadelphia: Lippincott, Williams & Wilkins, 2001, pp.
739-57.



inflammation of the abdominal cavity lining

OTHER



abscess



problems related to general anesthesia

Rare complications include:

Laparoscopy is generally not used in patients
with certain heart or lung conditions, or in those
who have some intestinal disorders, such as bowel
obstruction.
GALE ENCYCLOPEDIA OF MEDICINE

Iannitti, David A. ‘‘The Role of Laparoscopy in the
Management of Pancreatic Cancer.’’ Home Journal
Library Index. March 23, 2001. [cited June 27, 2001].
<http://bioscience.org/1998/v3/e/iannitti/e181185.htm>.

Carol A. Turkington
Rhonda Cloos, R.N.
2161

Laparoscopy

Sometimes, additional small incisions are made to
insert other instruments that are used to lift the tubes
and ovaries for examination or to perform surgical
procedures.

Laryngeal cancer

Laryngeal cancer
Definition
Laryngeal cancer is cancer of the larynx or voice
box.

Description
The larynx is located where the throat divides into
the esophagus and the trachea. The esophagus is the
tube that takes food to the stomach. The trachea, or
windpipe, takes air to the lungs. The area where the
larynx is located is sometimes called the Adam’s apple.
The larynx has two main functions. It contains the
vocal cords, cartilage, and small muscles that make up
the voice box. When a person speaks, small muscles
tighten the vocal cords, narrowing the distance
between them. As air is exhaled past the tightened
vocal cords, it creates sounds that are formed into
speech by the mouth, lips, and tongue.
The second function of the larynx is to allow air to
enter the trachea and to keep food, saliva, and foreign
material from entering the lungs. A flap of tissue called
the epiglottis covers the trachea each time a person
swallows. This blocks foreign material from entering
the lungs. When not swallowing, the epiglottis
retracts, and air flows into the trachea. During treatment for cancer of the larynx, both of these functions
may be lost.
Cancers of the larynx develop slowly. About 95%
of these cancers develop from thin, flat cells similar to
skin cells called squamous epithelial cells. These cells
line the larynx. Gradually, the squamous epithelial
cells begin to change and are replaced with abnormal
cells. These abnormal cells are not cancerous but are
pre-malignant cells that have the potential to develop
into cancer. This condition is called dysplasia. Most
people with dysplasia never develop cancer. The condition simply goes away without any treatment, especially if the person with dysplasia stops smoking or
drinking alcohol.
The larynx is made up of three parts, the glottis,
the supraglottis, and the subglottis. Cancer can start in
any of these regions. Treatment and survival rates
depend on which parts of the larynx are affected and
whether the cancer has spread to neighboring areas of
the neck or distant parts of the body.
The glottis is the middle part of the larynx. It
contains the vocal cords. Cancers that develop on the
vocal cords are often diagnosed very early because
even small vocal cord tumors cause hoarseness. In
2162

addition, the vocal cords have no connection to the
lymphatic system. This means that cancers on the
vocal cord do not spread easily. When confined to
the vocal cords without any involvement of other
parts of the larynx, the cure rate for this cancer is
75% to 95%.
The supraglottis is the area above the vocal cords.
It contains the epiglottis, which protects the trachea
from foreign materials. Cancers that develop in this
region are usually not found as early as cancers of the
glottis because the symptoms are less distinct. The
supraglottis region has many connections to the lymphatic system, so cancers in this region tend to spread
easily to the lymph nodes and may spread to other parts
of the body (lymph nodes are small bean-shaped structures that are found throughout the body; they produce
and store infection-fighting cells). In 25% to 50% of
people with cancer in the supraglottal region, the cancer
has already spread to the lymph nodes by the time they
are diagnosed. Because of this, survival rates are lower
than for cancers that involve only the glottis.
The subglottis is the region below the vocal cords.
Cancer starting in the subglottis region is rare. When it
does, it is usually detected only after it has spread to
the vocal cords, where it causes obvious symptoms
such as hoarseness. Because the cancer has already
begun to spread by the time it is detected, survival
rates are generally lower than for cancers in other
parts of the larynx.
About 12,000 new cases of cancer of the larynx
develop in the United States each year. Each year,
about 3,900 die of the disease. Laryngeal cancer is
between four and five times more common in men
than in women. Almost all men who develop laryngeal
cancer are over age 55. Laryngeal cancer is about 50%
more common among African-American men than
among other Americans.
It is thought that older men are more likely to
develop laryngeal cancer than women because the
two main risk factors for acquiring the disease are
lifetime habits of smoking and alcohol abuse. More
men are heavy smokers and drinkers than women, and
more African-American men are heavy smokers than
other men in the United States. However, as smoking
becomes more prevalent among women, it seems likely
that more cases of laryngeal cancer in females will
be seen.

Causes and symptoms
Laryngeal cancer develops when the normal cells
lining the larynx are replaced with abnormal cells
GALE ENCYCLOPEDIA OF MEDICINE

The symptoms of laryngeal cancer depend on the
location of the tumor. Tumors on the vocal cords are
rarely painful, but cause hoarseness. Anyone who is
continually hoarse for more than two weeks or who
has a cough that does not go away should be checked
by a doctor.
Tumors in the supraglottal region above the vocal
cords often cause more, but less distinct symptoms.
These include:


persistent sore throat



pain when swallowing



difficulty swallowing or frequent choking on food



bad breath



lumps in the neck



persistent ear pain (called referred pain; the source of
the pain is not the ear)



change in voice quality

Tumors that begin below the vocal cords are rare,
but may cause noisy or difficult breathing. All the
symptoms above can also be caused other cancers as
well as by less seriousness illnesses. However, if these
symptoms persist, it is important to see a doctor and
find their cause, because the earlier cancer treatment
begins, the more successful it is.

Diagnosis
On the first visit to a doctor for symptoms that
suggest laryngeal cancer, the doctor first takes a complete medical history, including family history of cancer and lifestyle information about smoking and
alcohol use. The doctor also does a physical examination, paying special attention to the neck region for
lumps, tenderness, or swelling.
The next step is examination by an otolaryngologist, or ear, nose, and throat (ENT) specialist. This
doctor also performs a physical examination, but in
addition will also want to look inside the throat at the
larynx. Initially, the doctor may spray a local anesthetic on the back of the throat to prevent gagging,
GALE ENCYCLOPEDIA OF MEDICINE

then use a long-handled mirror to look at the larynx
and vocal cords. This examination is done in the doctor’s office. It may cause gagging but is usually
painless.
A more extensive examination involves a laryngoscopy. In a laryngoscopy, a lighted fiberoptic tube
called a laryngoscope that contains a tiny camera is
inserted through the patient’s nose and mouth and
snaked down the throat so that the doctor can see
the larynx and surrounding area. This procedure can
be done with a sedative and local anesthetic in a doctor’s office. More often, the procedure is done in an
outpatient surgery clinic or hospital under general
anesthesia. This allows the doctor to use tiny clips on
the end of the laryngoscope to take biopsies (tissue
samples) of any abnormal-looking areas.
Laryngoscopies are normally painless and take
about one hour. Some people find their throat feels
scratchy after the procedure. Since laryngoscopies
are done under sedation, patients should not drive
immediately after the procedure, and should have
someone available to take them home. Laryngoscopy is a standard procedure that is covered by
insurance.
The locations of the samples taken during the
laryngoscopy are recorded, and the samples are then
sent to the laboratory where they are examined under
the microscope by a pathologist who specializes in
diagnosing diseases through cell samples and laboratory tests. It may take several days to get the results.
Based on the findings of the pathologist, cancer can be
diagnosed and staged.
Once cancer is diagnosed, other tests will probably be done to help determine the exact size and
location of the tumors. This information is helpful in
determining which treatments are most appropriate.
These tests may include:


Endoscopy. Similar to a laryngoscopy, this test is
done when it appears that cancer may have spread
to other areas, such as the esophagus or trachea.



Computed tomography (CT or CAT) scan. Using
x-ray images taken from several angles and computer
modeling, CT scans allow parts of the body to be
seen as a cross section. This helps locate and size the
tumors, and provides information on whether they
can be surgically removed.



Magnetic resonance imaging (MRI). MRI uses magnets and radio waves to create more detailed crosssectional scans than computed tomography. This
detailed information is needed if surgery on the
larynx area is planned.
2163

Laryngeal cancer

(dysplasia) that become malignant and reproduce to
form tumors. The development of dysplasia is strongly
linked to life-long habits of smoking and heavy use of
alcohol. The more a person smokes, the greater the
risk of developing laryngeal cancer. It is unusual for
someone who does not smoke or drink to develop
cancer of the larynx. Occasionally, however, people
who inhale asbestos particles, wood dust, paint or
industrial chemical fumes over a long period of time
develop the disease.

Laryngeal cancer



Barium swallow. Barium is a substance that, unlike
soft tissue, shows up on x rays. Swallowed barium
coats the throat and allows x-ray pictures to be made
of the tissues lining the throat.

STAGE III. Either of the following may be true:


The cancer has not spread outside of the larynx, but
the vocal cords cannot move normally, or the cancer
has spread to tissues next to the larynx.



The cancer has spread to one lymph node on the
same side of the neck as the cancer, and the lymph
node measures no more than 3 centimeters ( just over
1 inch).



Chest x ray. Done to determine if cancer has spread
to the lungs. Since most people with laryngeal cancer
are smokers, the risk of also having lung cancer or
emphysema is high.



Fine needle aspiration (FNA) biopsy. If any lumps
on the neck are found, a thin needle is inserted into
the lump, and some cells are removed for analysis by
the pathologist.



Additional blood and urine tests. These tests do not
diagnose cancer, but help to determine the patient’s
general health and provide information to determine
which cancer treatments are most appropriate.

The cancer has spread to tissues around the larynx,
such as the pharynx or the tissues in the neck. The
lymph nodes in the area may or may not contain
cancer.



The cancer has spread to more than one lymph node
on the same side of the neck as the cancer, to lymph
nodes on one or both sides of the neck, or to any
lymph node that measures more than 6 centimeters
(over 2 inches).



The cancer has spread to other parts of the body.



STAGE IV. Any of the following may be true:

Treatment
Staging
Once cancer of the larynx is found, more tests will
be done to find out if cancer cells have spread to other
parts of the body. This is called staging. A doctor
needs to know the stage of the disease to plan treatment. In cancer of the larynx, the definitions of the
early stages depend on where the cancer started.

RECURRENT. Recurrent disease means that the
cancer has come back (recurred) after it has been
treated. It may come back in the larynx or in another
part of the body.

STAGE I. The cancer is only in the area where it
started and has not spread to lymph nodes in the area
or to other parts of the body. The exact definition of
stage I depends on where the cancer started, as
follows:

Treatment is based on the stage of the cancer as
well as its location and the health of the individual.
Generally, there are three types of treatments for cancer of the larynx. These are surgery, radiation, and
chemotherapy. They can be used alone or in combination based in the stage of the caner. Getting a second
opinion after the cancer has been staged can be very
helpful in sorting out treatment options and should
always be considered.



Supraglottis: The cancer is only in one area of the
supraglottis and the vocal cords can move normally.



Glottis: The cancer is only in the vocal cords and the
vocal cords can move normally.



Subglottis: The cancer has not spread outside of the
subglottis.

STAGE II. The cancer is only in the larynx and has
not spread to lymph nodes in the area or to other parts
of the body. The exact definition of stage II depends
on where the cancer started, as follows:


Supraglottis: The cancer is in more than one area of
the supraglottis, but the vocal cords can move
normally.



Glottis: The cancer has spread to the supraglottis or
the subglottis or both. The vocal cords may or may
not be able to move normally.



Subglottis: The cancer has spread to the vocal cords,
which may or may not be able to move normally.

2164

Treatment

SURGERY. The goal of surgery is to cut out the
tissue that contains malignant cells. There are several
common surgeries to treat laryngeal cancer.

Stage III and stage IV cancers are usually treated
with total laryngectomy. This is an operation to
remove the entire larynx. Sometimes other tissues
around the larynx are also removed. Total laryngectomy removes the vocal cords. Alternate methods of
voice communication must be learned with the help of
a speech pathologist. Laryngectomy is treated in depth
as a separate entry in this volume.
Smaller tumors are sometimes treated by partial
laryngectomy. The goal is to remove the cancer but
save as much of the larynx (and corresponding speech
capability) as possible. Very small tumors or cancer in
situ are sometimes successfully treated with laser
GALE ENCYCLOPEDIA OF MEDICINE

Advanced cancer (Stages III and IV) that has
spread to the lymph nodes often requires an operation
called a neck dissection. The goal of a neck dissection
is to remove the lymph nodes and prevent the cancer
from spreading. There are several forms of neck dissection. A radical neck dissection is the operation that
removes the most tissue.
Several other operations are sometimes performed because of laryngeal cancer. A tracheotomy is
a surgical procedure in which an artificial opening is
made in the trachea (windpipe) to allow air into the
lungs. This operation is necessary if the larynx is
totally removed. A gastrectomy tube is a feeding tube
placed through skin and directly into the stomach. It is
used to give nutrition to people who cannot swallow or
whose esophagus is blocked by a tumor. People who
have a total laryngectomy usually do not need a gastrectomy tube if their esophagus remains intact.
RADIATION. Radiation therapy uses high-energy

rays, such as x rays or gamma rays, to kill cancer
cells. The advantage of radiation therapy is that it
preserves the larynx and the ability to speak. The
disadvantage is that it may not kill all the cancer
cells. Radiation therapy can be used alone in early
stage cancers or in combination with surgery.
Sometimes it is tried first with the plan that if it fails
to cure the cancer, surgery still remains an option.
Often, radiation therapy is used after surgery for
advanced cancers to kill any cells the surgeon might
not have removed.

CHEMOTHERAPY. Chemotherapy is the use of
drugs to kill cancer cells. Unlike radiation therapy,
which is targeted to a specific tissue, chemotherapy
drugs are either taken by mouth or intravenously
(through a vein) and circulate throughout the whole
body. They are used mainly to treat advanced laryngeal cancer that is inoperable or that has metastasized
to a distant site. Chemotherapy is often used after
surgery or in combination with radiation therapy.
Clinical trials are underway to determine the best
combination of treatments for advanced cancer.

The two most common chemotherapy drugs used
to treat laryngeal cancer are cisplatin and 5-fluorouracil
(5-FU). There are many side effects associated with
chemotherapy drugs, including nausea and vomiting,
loss of appetite, hair loss, diarrhea, and mouth sores.
Chemotherapy can also damage the blood-producing
cells of the bone marrow, which can result in low
blood cell counts, increased chance of infection, and
abnormal bleeding or bruising.

Alternative treatment
Alternative and complementary therapies range
from herbal remedies, vitamin supplements, and special diets to spiritual practices, acupuncture, massage,
and similar treatments. When these therapies are used
in addition to conventional medicine, they are called
complementary therapies. When they are used instead
of conventional medicine, they are called alternative
therapies.

There are two types of radiation therapy. External
beam radiation therapy focuses rays from outside the
body on the cancerous tissue. This is the most common type of radiation therapy used to treat laryngeal
cancer. With internal radiation therapy, also called
brachytherapy, radioactive materials are placed
directly on the cancerous tissue. This type of radiation
therapy is a much less common treatment for laryngeal cancer.

Complementary or alternative therapies are
widely used by people with cancer. One large study
published in the Journal of Clinical Oncology in July,
2000 found that 83% of all cancer patients studied
used some form of complementary or alternative
medicine as part of their cancer treatment. No specific
alternative therapies have been directed toward laryngeal cancer. However, good nutrition and activities
that reduce stress and promote a positive view of life
have no unwanted side-effects and appear to be beneficial in boosting the immune system in fighting
cancer.

External radiation therapy is given in doses called
fractions. A common treatment involves giving fractions five days a week for seven weeks. Clinical trials
are underway to determine the benefits of accelerating
the delivery of fractions (accelerated fractionation) or
dividing fractions into smaller doses given more than
once a day (hyperfractionation). Side effects of radiation therapy include dry mouth, sore throat, hoarseness, skin problems, trouble swallowing, and
diminished ability to taste.

Unlike traditional pharmaceuticals, complementary and alternative therapies are not evaluated by the
United States Food and Drug Administration (FDA)
for either safety or effectiveness. These therapies may
have interactions with traditional pharmaceuticals.
Patients should be wary of ‘‘miracle cures’’ and notify
their doctors if they are using herbal remedies, vitamin
supplements or other unprescribed treatments.
Alternative and experimental treatments normally
are not covered by insurance.

GALE ENCYCLOPEDIA OF MEDICINE

2165

Laryngeal cancer

excision surgery. In this type of surgery, a narrowlytargeted beam of light from a laser is used to remove
the cancer.

Laryngectomy

KEY TERMS
Dysplasia—The abnormal change in size, shape or
organization of adult cells.
Lymph—Clear, slightly yellow fluid carried by a
network of thin tubes to every part of the body.
Cells that fight infection are carried in the lymph.
Lymphatic system—Primary defense against infection in the body. The lymphatic system consists of
tissues, organs, and channels (similar to veins) that
produce, store, and transport lymph and white
blood cells to fight infection.
Lymph nodes—Small, bean-shaped collections of
tissue found in a lymph vessel. They produce cells
and proteins that fight infection, and also filter
lymph. Nodes are sometimes called lymph glands.
Metastasize—Spread of cells from the original site
of the cancer to other parts of the body where
secondary tumors are formed.
Malignant—Cancerous. Cells tend to reproduce
without normal controls on growth and form
tumors or invade other tissues.

balanced diet, seeking treatment for prolonged heartburn, and avoiding inhaling asbestos and chemical
fumes.
Resources
PERIODICALS

Ahmad, I., B. N. Kumar, K. Radford, J. O’Connell, and
A. J. Batch. ‘‘Surgical Voice Restoration Following
Ablative Surgery for Laryngeal and Hypopharyngeal
Carcinoma.’’ Journal or Laryngology and
Otolaryngology 114 (July 2000): 522–5.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta,
GA 30329. 800 (ACS)-2345. <http://
www.cancer.org>.
National Cancer Institute. Cancer Information Service.
Bldg. 31, Room 10A19, 9000 Rockville Pike, Bethesda,
MD 20892. (800) 4-CANCER. <http://
www.nci.nih.gov/cancerinfo/index.html>.
National Cancer Institute Office of Cancer Complementary
and Alternative Medicine. <http://
occam.nci.nih.gov>.
National Center for Complementary and Alternative
Medicine. P. O. Box 8218, Silver Spring, MD 209078281. (888) 644-6226. <http://nccam.nih.gov>.
OTHER

Prognosis
Cure rates and survival rates can predict group
outcomes, but can never precisely predict the outcome
for a single individual. However, the earlier laryngeal
cancer is discovered and treated, the more likely it will
be cured.
Cancers found in stage 0 and stage 1 have a 75%
to 95% cure rate depending on the site. Late stage
cancers that have metastasized have a very poor survival rate, with intermediate stages falling somewhere
in between. People who have had laryngeal cancer are
at greatest risk for recurrence (having cancer come
back), especially in the head and neck, during the
first two to three years after treatment. Check-ups
during the first year are needed every other month,
and four times a year during the second year. It is rare
for laryngeal cancer to recur after five years of being
cancer-free.

‘‘Laryngeal Cancer.’’ CancerNet. July 19, 2001. <http://
www.graylab.ac.uk/cancernet/
201519.html#3_STAGEEXPLANATION>.
‘‘What you Need to Know About Cancer of the Larynx.’’
CancerNet November 2000. [cited July 19, 2001].
<http://www.cancernet.nci.nih.gov>.

Tish Davidson, A.M.

Laryngeal cancer see Head and neck cancer

Laryngectomy
Definition
Laryngectomy is the partial or complete surgical
removal of the larynx, usually as a treatment for
cancer of the larynx.

Purpose
Prevention
By far, the most effective way to prevent laryngeal
cancer is not to smoke. Smokers who quit smoking
also significantly decrease their risk of developing the
disease. Other ways to prevent laryngeal cancer
include limiting the use of alcohol, eating a well2166

Normally a laryngectomy is performed to remove
tumors or cancerous tissue. In rare cases, it may be
done when the larynx is badly damaged by gunshot,
automobile injuries, or similar violent accidents.
Laryngectomies can be total or partial. Total laryngectomies are done when cancer is advanced. The
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Laryngectomy is done only after cancer of the
larynx has been diagnosed by a series of tests that
allow the otolaryngologist (a specialist often called
an ear, nose, and throat doctor) to look into the throat
and take tissue samples (biopsies) to confirm and stage
the cancer. People need to be in good general health to
undergo a laryngectomy, and will have standard preoperative blood work and tests to make sure they are
able to safely withstand the operation.

Description
The larynx is located slightly below the point
where the throat divides into the esophagus, which
takes food to the stomach, and the trachea (windpipe),
which takes air to the lungs. Because of its location,
the larynx plays a critical role in normal breathing,
swallowing, and speaking. Within the larynx, vocal
folds (often called vocal cords) vibrate as air is exhaled
past, thus creating speech. The epiglottis protects the
trachea, making sure that only air gets into the lungs.
When the larynx is removed, these functions are lost.
Once the larynx is removed, air can no longer flow
into the lungs. During this operation, the surgeon
removes the larynx through an incision in the neck.
The surgeon also performs a tracheotomy. He makes
an artificial opening called a stoma in the front of the
neck. The upper portion of the trachea is brought to
the stoma and secured, making a permanent alternate
way for air to get to the lungs. The connection between
the throat and the esophagus is not normally affected,
so after healing, the person whose larynx has been
removed (called a laryngectomee) can eat normally.
However, normal speech is no longer possible. Several
alternate means of vocal communication can be
learned with the help of a speech pathologist.

Preparation
As with any surgical procedure, the patient will
be required to sign a consent form after the procedure is thoroughly explained. Many patients prefer
a second opinion, and some insurers require it.
GALE ENCYCLOPEDIA OF MEDICINE

Blood and urine studies, along with chest x ray
and EKG may be ordered as the doctor deems
necessary. The patient also has a pre-operative
meeting with an anesthesiologist. If a complete
laryngectomy is planned, it may be helpful to
meet with a speech pathologist and/or an established laryngectomee for discussion of post-operative expectations and support.

Aftercare
A person undergoing a laryngectomy spends
several days in intensive care (ICU) and receives
intravenous (IV) fluids and medication. As with
any major surgery, the blood pressure, pulse, and
respirations are monitored regularly. The patient is
encouraged to turn, cough, and deep breathe to
help mobilize secretions in the lungs. One or more
drains are usually inserted in the neck to remove
any fluids that collect. These drains are removed
after several days.
It takes two to three weeks for the tissues of the
throat to heal. During this time, the laryngectomee
cannot swallow food and must receive nutrition
through a tube inserted through the nose and down
the throat into the stomach. During this time, even
people with partial laryngectomies are unable to
speak.
When air is drawn in normally through the nose, it
is warmed and moistened before it reaches the lungs.
When air is drawn in through the stoma, it does not
have the opportunity to be warmed and humidified. In
order to keep the stoma from drying out and becoming
crusty, laryngectomees are encouraged to breathe artificially humidified air. The stoma is usually covered
with a light cloth to keep it clean and to keep
unwanted particles from accidentally entering the
lungs. Care of the stoma is extremely important,
since it is the person’s only way to get air to the
lungs. After a laryngectomy, a healthcare professional
will teach the laryngectomee and his or her caregivers
how to care for the stoma.
Immediately after a laryngectomy, an alternate
method of communication such as writing notes, gesturing, or pointing must be used. A partial laryngectomy patient will gradually regain some speech several
weeks after the operation, but the voice may be hoarse,
weak, and strained. A speech pathologist will work
with a complete laryngectomee to establish new ways
of communicating.
There are three main methods of vocalizing after
a total laryngectomy. In esophageal speech the
2167

Laryngectomy

entire larynx is removed. Often if the cancer has
spread, other surrounding structures in the neck,
such as lymph nodes, are removed at the same time.
Partial laryngectomies are done when cancer is limited
to one spot. Only the area with the tumor is removed.
Laryngectomies may also be performed when other
cancer treatment options, such as radiation or
chemotherapy, fail.

Laryngectomy

KEY TERMS
Larynx—Also known as the voice box, the larynx is
composed of cartilage that contains the apparatus
for voice production. This includes the vocal cords
and the muscles and ligaments that move the cords.
Lymph nodes—Accumulations of tissue along a
lymph channel, which produce cells called lymphocytes that fight infection.
Tracheostomy—A surgical procedure in which an
artificial opening is made in the trachea (windpipe)
to allow air into the lungs.
A pathology photograph of an extracted tumor found on the
larynx. (Custom Medical Stock Photo. Reproduced by
permission.)

Risks
laryngectomee learns how to ‘‘swallow’’ air down into
the esophagus and creates sounds by releasing the air.
This method requires quite a bit of coordination and
learning, and produces short bursts (7 or 8 syllables) of
low-volume sound.
Tracheoesophageal speech diverts air through a
hole in the trachea made by the surgeon. The air then
passes through an implanted artificial voice prosthesis
(a small tube that makes a sound when air goes
through it). Recent advances have been made in
implanting voice prostheses that produce good voice
quality.
The third method of artificial sound communication involves using a hand-held electronic device that
translates vibrations into sounds. There are several
different styles of these devices, but all require the
use of at least one hand to hold the device to the
throat. The choice of which method to use depends
on many things including the age and health of the
laryngectomee, and whether other parts of the mouth,
such as the tongue, have also been removed.
Many patients resume daily activities after surgery. Special precautions must be taken during showering or shaving. Special instruction and equipment is
also required for those who wish to swim or water ski,
as it is dangerous for water to enter the windpipe and
lungs through the stoma.
Regular follow-up visits are important following
treatment for cancer of the larynx because there is a
higher-than-average risk of developing a new cancer in
the mouth, throat, or other regions of the head or
neck. Many self-help and support groups are available
to help patients meet others who face similar
problems.
2168

Laryngectomy is often successful in curing early
stage cancers. However it does cause lifestyle changes.
Laryngectomees must learn new ways of speaking. They
must be continually concerned about the care of their
stoma. Serious infections can occur if water or other
foreign material enters the lungs through an unprotected
stoma. Also, women who undergo partial laryngectomy
or who learn some types of artificial speech will have a
deep voice similar to that of a man. For some women
this presents psychological challenges.

Normal results
Ideally, removal of the larynx will remove all cancerous material. The person will recover from the
operation, make lifestyle adjustments, and return to
an active life.

Abnormal results
Sometimes cancer has spread to surrounding tissues
and it is necessary to remove lymph nodes, parts of the
tongue, or other cancerous tissues. As with any major
operation, post- surgical infection is possible. Infection
is of particular concern to laryngectomees who have
chosen to have a voice prosthesis implanted, and is one
of the major reasons for having to remove the device.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800) ACS -2345. <http://
www.cancer.org>.
Cancer Information Service. National Cancer Institute,
Building 31, Room 10A19, 9000 Rockville Pike,
Bethesda, MD 20892. (800) 4-CANCER. <http://
www.nci.nih.gov/cancerinfo/index.html>.
GALE ENCYCLOPEDIA OF MEDICINE

Kathleen D. Wright, RN
Tish Davidson, AM

Laryngitis
Definition
Laryngitis is caused by inflammation of the
larynx, resulting in hoarseness of the voice.

Description
When air is breathed in (inspired), it passes
through the nose and the nasopharynx or through
the mouth and the oropharynx. These are both connected to the larynx, a tube made of cartilage. The
vocal cords, responsible for setting up the vibrations
necessary for speech, are located within the larynx.
The air continues down the larynx to the trachea.
The trachea then splits into two branches, the left
and right bronchi (bronchial tubes). These bronchi
branch into smaller air tubes which run within the
lungs, leading to the small air sacs of the lungs
(alveoli).
Either food, liquid, or air may be taken in through
the mouth. While air goes into the larynx and the
respiratory system, food and liquid are directed into
the tube leading to the stomach, the esophagus.
Because food or liquid in the bronchial tubes or
lungs could cause a blockage or lead to an infection,
the airway must be protected. The epiglottis is a leaflike piece of cartilage extending upwards from the
larynx. The epiglottis can close down over the larynx
when someone is eating or drinking, preventing these
substances from entering the airway.
In laryngitis, the tissues below the level of the
epiglottis are swollen and inflamed. This causes swelling around the area of the vocal cords, so that they
cannot vibrate normally. A hoarse sound to the voice
is very characteristic of laryngitis. Laryngitis is a very
GALE ENCYCLOPEDIA OF MEDICINE

common problem, and often occurs during the course
of an upper respiratory tract infection (cold).

Causes and symptoms
Laryngitis is caused almost 100% of the time by a
virus. The same viruses which cause the majority of
simple upper respiratory infections (colds, etc.) are
responsible for laryngitis. These include parainfluenzae virus, influenza virus, respiratory syncytial virus,
rhinovirus, coronavirus, and echovirus. Extremely
rarely, bacteria such as Group A streptococcus,
M. catarrhalis, or that which causes tuberculosis may
cause laryngitis. In people with faulty immune systems
(particular due to acquired immunodeficiency syndrome, or AIDS), infections with fungi may be responsible for laryngitis.
Symptoms usually begin along with, or following,
symptoms of a cold. A sore, scratchy throat, fever,
runny nose, achiness, and fatigue may all occur.
Difficulty swallowing sometimes occurs with streptococcal infections. The patient may cough and wheeze.
Most characteristically, the patient’s voice will sound
strained, hoarse, and raspy.
In extremely rare cases, the swelling of the larynx
may cause symptoms of airway obstruction. This is
more common in infants, because the diameter of their
airways is so small. In that case, the baby may have a
greatly increased respiratory rate, and exhibit loud
high-pitched sounds with breathing (called stridor).

Diagnosis
Diagnosis is usually made by learning the history
of a cold followed by hoarseness. The throat usually
appears red and somewhat swollen. Listening to the
chest and back with a stethoscope may reveal some
harsh wheezing sounds with inspiration (breathing in).
In long-standing (chronic laryngitis), tuberculosis
may be suspected. Using a scope called a laryngoscope, examination of the airway will show redness,
swelling, small bumps of tissue called nodules, and
irritated pits in the tissue called ulcerations. Special
skin testing (TB testing) will reveal that the individual
has been exposed to the bacteria causing TB.

Treatment
Treatment of a simple, viral laryngitis simply
addresses the symptoms. Gargling with warm salt
water, pain relievers such as acetaminophen, the use
of vaporizers to create moist air, and rest will help the
illness resolve within a week.
2169

Laryngitis

International Association of Laryngectomees(IAL). 7440
North Shadeland Ave., Suite 100, Indianapolis, IN
46250. <http://www.larynxlink.com/>.
National Institute on Deafness and Other Communication
Disorders. National Institutes of Health, 31 Center
Drive, MSC 2320, Bethesda, MD 20892-2320. <http://
www.nidcd.nih.gov>.
The Voice Center at Eastern Virginia Medical School.
Norfolk, VA 23507. <http://www.voice-center.com>.

Laryngoscopy

(Glycyrrhiza glabra). These are used for gargling, and
are said to reduce pain. Echinacea ( Echinacea spp.)
tincture taken in water every hour for 48 hours is
recommended to boost the immune system. Antiviral
herbs, including usnea (Usnea spp.), lomatium
(Lomatium dissectum), and ligusticum (Ligusticum
porteri), may help hasten recovery from laryngitis.
Homeopathic remedies are recommended based on
the patient’s symptoms. Some people may get relief
from placing cold compresses on the throat.

Prognosis
An endoscopic view of a patient’s vocal cords with laryngitis.
(Custom Medical Stock Photo. Reproduced by permission.)

Prognosis for laryngitis is excellent. Recovery is
complete, and usually occurs within a week’s time.

Prevention

KEY TERMS
Epiglottis—A leaf-like piece of cartilage extending
upwards from the larynx, which can close like a lid
over the trachea to prevent the airway from receiving any food or liquid being swallowed.
Larynx—The part of the airway lying between the
pharynx and the trachea.
Nasopharynx—The part of the airway into which
the nose leads.
Oropharynx—The part of the airway into which
the mouth leads.
Trachea—The part of the airway which leads into
the bronchial tubes.

In an infant who is clearly struggling for air, it
may be necessary to put in an artificial airway for a
short period of time. This is very rarely needed.
An individual with tubercular laryngitis is treated
with a combination of medications used to treat classic
TB. In people with fungal laryngitis, a variety of antifungal medications are available.

Alternative treatment
Alternative treatments include aromatherapy
inhalations made with benzoin, lavender, frankincense, thyme, and sandalwood. Decoctions (extracts
made by boiling an herb in water) or infusions
(extracts made by steeping an herb in boiling water)
can be made with red sage (Salvia officinalis var. rubra)
and yarrow (Achillea millefolium) or with licorice
2170

Prevention of laryngitis is the same as for any
upper respiratory infections. The only way to even
attempt to prevent such illnesses is by good handwashing, and by avoiding situations where one might come
in contact with people who might be sick. However,
even with relatively good hygiene practices, most people will get about five to six colds per year. It is
unpredictable which of these may lead to laryngitis.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.

Rosalyn Carson-DeWitt, MD

Laryngoscopy
Definition
Laryngoscopy refers to a procedure used to view
the inside of the larynx (the voice box).

Description
The purpose and advantage of seeing inside the
larynx is to detect tumors, foreign bodies, nerve or
structural injury, or other abnormalities. Two methods
allow the larynx to be seen directly during the examination. In one, a flexible tube with a fiber-optic device is
threaded through the nasal passage and down into the
throat. The other method uses a rigid viewing tube
GALE ENCYCLOPEDIA OF MEDICINE

Laser surgery

Endoscopic tube—a tube that is inserted into a
hollow organ permitting a physician to see the
inside it.

passed directly from the mouth, through the throat,
into the larynx. A light and lens affixed to the endoscope are used in both methods. The endoscopic tube
may also be equipped to suction debris or remove
material for biopsy. Bronchoscopy is a similar, but
more extensive procedure in which the tube is continued
through the larynx, down into the trachea and bronchi.

Preparation
Laryngoscopy is done in the hospital with a local
anesthetic spray to minimize discomfort and suppress
the gag reflex. Patients are requested not to eat for
several hours before the examination.

Aftercare
If the throat is sore, soothing liquids or lozenges
will probably relieve any temporary discomfort.

Risks
This procedure carries no serious risks, although
the patient may experience soreness of the throat or
cough up small amounts of blood until the irritation
subsides.

Normal results
A normal result would be the absence of signs of
disease or damage.

Definition
Laser (light amplification by stimulated emission
of radiation) surgery uses an intensely hot, precisely
focused beam of light to remove or vaporize tissue and
control bleeding in a wide variety of non-invasive and
minimally invasive procedures.

Purpose
Laser surgery is used to:


Cut or destroy tissue that is abnormal or diseased
without harming healthy, normal tissue



Shrink or destroy tumors and lesions



Cauterize (seal) blood vessels to prevent excessive
bleeding.

Precautions
Anyone who is thinking about having laser surgery should ask his doctor to:


Explain why laser surgery is likely to be more beneficial than traditional surgery



Describe his experience in performing the laser
procedure the patient is considering.

Because some lasers can temporarily or permanently discolor the skin of Blacks, Asians, and
Hispanics, a dark-skinned patient should make sure
that his surgeon has successfully performed laser
procedures on people of color.
Some types of laser surgery should not be performed on pregnant women or on patients with severe
cardiopulmonary disease or other serious health
problems.

Description

Abnormal results
An abnormal finding, such as a tumor or an object
lodged in the tissue, would either be removed or
described for further medical attention.
Jill S. Lasker

Larynx removal see Laryngectomy
Laser-assisted in-situ keratomileusis see
Photorefractive keratectomy and
laser-assisted inGALE ENCYCLOPEDIA OF MEDICINE

The first working laser was introduced in 1960.
The device was initially used to treat diseases and
disorders of the eye, whose transparent tissues gave
ophthalmic surgeons a clear view of how the narrow,
concentrated beam was being directed. Dermatologic
surgeons also helped pioneer laser surgery, and developed and improved upon many early techniques and
more refined surgical procedures.
Types of lasers
The three types of lasers most often used in medical treatment are the:
2171

Laser surgery

KEY TERMS

Laser surgery



Carbon dioxide (CO2) laser. Primarily a surgical
tool, this device converts light energy to heat strong
enough to minimize bleeding while it cuts through or
vaporizes tissue.



Neodymium:yttrium-aluminum-garnet (Nd:YAG)
laser. Capable of penetrating tissue more deeply
than other lasers, the Nd:YAG makes blood clot
quickly and can enable surgeons to see and work on
parts of the body that could otherwise be reached
only through open (invasive) surgery.



Argon laser. This laser provides the limited penetration needed for eye surgery and superficial skin
disorders. In a special procedure known as photodynamic therapy (PDT), this laser uses light-sensitive
dyes to shrink or dissolve tumors.
Laser applications

Sometimes described as ‘‘scalpels of light,’’ lasers
are used alone or with conventional surgical instruments in a diverse array of procedures that:

tonsils, remove or transplant hair, and relieve pain
and restore function in patients who are too weak to
undergo major surgery. Lasers are also used to treat:


angina (chest pain)



cancerous or non-cancerous tumors that cannot be
removed or destroyed



cold and canker sores, gum disease, and tooth sensitivity or decay



ectopic pregnancy (development of a fertilized egg
outside the uterus)



endometriosis



fibroid tumors



gallstones



glaucoma, mild-to-moderate nearsightedness and
astigmatism, and other conditions that impair sight



migraine headaches



non-cancerous enlargement of the prostate gland



improve appearance



nosebleeds



relieve pain



ovarian cysts



restore function



ulcers



save lives



varicose veins



warts



numerous other conditions, diseases, and disorders

Laser surgery is often standard operating procedure for specialists in:


cardiology



dentistry



dermatology



gastroenterology (treatment of disorders of the stomach and intestines)



gynecology



neurosurgery



oncology (cancer treatment)



ophthalmology (treatment of disorders of the eye)



orthopedics (treatment of disorders of bones, joints,
muscles, ligaments, and tendons)



otolaryngology (treatment of disorders of the ears,
nose, and throat)



pulmonary care (treatment of disorders of the
respiratory system



urology (treatment of disorders of the urinary tract
and of the male reproductive system)

Routine uses of lasers include erasing birthmarks,
skin discoloration, and skin changes due to aging, and
removing benign, precancerous, or cancerous tissues
or tumors. Lasers are used to stop snoring, remove
2172

Advantages of laser surgery
Often referred to as ‘‘bloodless surgery,’’ laser
procedures usually involve less bleeding than conventional surgery. The heat generated by the laser keeps
the surgical site free of germs and reduces the risk of
infection. Because a smaller incision is required, laser
procedures often take less time (and cost less money)
than traditional surgery. Sealing off blood vessels and
nerves reduces bleeding, swelling, scarring, pain, and
the length of the recovery period.
Disadvantages of laser surgery
Although many laser surgeries can be performed
in a doctor’s office rather than in a hospital, the person
guiding the laser must be at least as thoroughly trained
and highly skilled as someone performing the same
procedure in a hospital setting. The American
Society for Laser Medicine and Surgery, Inc. urges
that:


All operative areas be equipped with oxygen and
other drugs and equipment required for cardiopulmonary resuscitation (CPR)
GALE ENCYCLOPEDIA OF MEDICINE

Laser surgery

Cosmetic laser surgery in progress. The wavelengths of the laser’s light can be matched to a specific target,
enabling the physician to destroy the capillaries near the skin’s surface without damaging the surrounding tissue.
(Photograph by Will & Deni McIntyre, Photo Researchers, Inc. Reproduced by permission.)



Non-physicians performing laser procedures be
properly trained, licensed, and insured



Determines the patient’s general health and current
medical status



A qualified and experienced supervising physician be
able to respond to and manage unanticipated events
or other emergencies within five minutes of the time
they occur



Describes how the patient has responded to other
illnesses, hospital stays, and diagnostic or therapeutic procedures



Clarifies what the patient expects the outcome of the
procedure to be.



Emergency transportation to a hospital or other
acute-care facility be available whenever laser surgery is performed in a non-hospital setting.

Imprecisely aimed lasers can burn or destroy
healthy tissue.

Preparation
Because laser surgery is used to treat so many
dissimilar conditions, the patient should ask his physician for detailed instructions about how to prepare
for a specific procedure. Diet, activities, and medications may not have to be limited prior to surgery, but
some procedures require a physical examination and a
medical history that:
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
Most laser surgeries can be performed on an outpatient basis, and patients are usually permitted to
leave the hospital or medical office when their vital
signs have stabilized. A patient who has been sedated
should not be discharged:


Until he has recovered from the anesthesia and
knows who and where he is



Unless he is accompanied by a responsible adult.

The doctor may prescribe analgesic (painrelieving) medication, and should provide easy-tounderstand written instructions that describe how the
2173

Laser surgery

patient’s recovery should progress and what to do in
case complications or emergency arise.

Risks
Like traditional surgery, laser surgery can be complicated by:


hemorrhage



infection



perforation (piercing) of an organ or tissue

Laser surgery can also involve risks that are not
associated with traditional surgical procedures. Being
careless or not practicing safe surgical techniques can
severely burn the patient’s lungs or even cause them to
explode. Patients must wear protective eye shields
while undergoing laser surgery on any part of the
face near the eyes or eyelids, and the United States
Food and Drug Administration (FDA) has said that
both doctors and patients must use special protective
eyewear whenever a CO2 laser is used.
Laser beams can burn or destroy healthy tissue,
cause injuries that are painful and sometimes permanent, and actually compound problems they are supposed to solve. Errors or inaccuracies in laser surgery
can worsen a patient’s vision, for example, and lasers
can scar and even change the skin color of some patients.

Normal results
The nature and severity of the problem, the skill of
the surgeon performing the procedure, and the
patient’s general health and realistic expectations are
among the factors that influence the outcome of laser
surgery. Successful procedures can enable patients to:


feel better



look younger



enjoy longer, fuller, more active lives

A patient who is considering any kind of laser surgery should ask his doctor to provide detailed information about what the outcome of the surgery is expected to
be, what the recovery process will involve, and how long
it will probably be before he regains a normal appearance and can resume his normal activities.

KEY TERMS
Argon—A colorless, odorless gas.
Astigmatism—A condition in which one or both
eyes cannot filter light properly and images appear
blurred and indistinct.
Canker sore—A blister-like sore on the inside of the
mouth that can be painful but is not serious.
Carbon dioxide—A heavy, colorless gas that dissolves in water.
Cardiopulmonary resuscitation—An emergency
procedure used to restore circulation and prevent
brain death to a person who has collapsed, is
unconscious, is not breathing, and has no pulse.
Cauterize—To use heat or chemicals to stop bleeding, prevent the spread of infection, or destroy
tissue.
Cornea—The outer, transparent lens that covers the
pupil of the eye and admits light.
Endometriosis—An often painful gynecologic condition in which endometrial tissue migrates from
the inside of the uterus to other organs inside and
beyond the abdominal cavity.
Glaucoma—A disease of the eye in which
increased pressure within the eyeball can cause
gradual loss of vision.
Invasive surgery—A form of surgery that involves
making an incision in the patient’s body and inserting instruments or other medical devices into it.
Nearsightedness—A condition in which one or
both eyes cannot focus normally, causing objects
at a distance to appear blurred and indistinct. Also
called myopia.
Ovarian cyst—A benign or malignant growth on an
ovary. An ovarian cyst can disappear without treatment or become extremely painful and have to be
surgically removed.
Vaporize—To dissolve solid material or convert it
into smoke or gas.
Varicose veins—Swollen, twisted veins, usually
occurring in the legs, that occur more often in
women than in men.

Abnormal results
A person who is considering any type of laser
surgery should ask his doctor to provide specific and
detailed information about what could go wrong during the procedure and what the negative impact on the
patient’s health or appearance might be.
2174

Lighter or darker skin may appear, for example,
when a laser is used to remove sun damage or age spots
from an olive-skinned or dark-skinned individual.
This abnormal pigmentation may or may not disappear in time.
GALE ENCYCLOPEDIA OF MEDICINE



increase sensitivity to light or glare



reduce night vision



permanently cloud vision, or cause sharpness of
vision to decline throughout the day
Signs of infection following laser surgery include:



burning



crusting of the skin



itching



pain



scarring



severe redness



swelling

fewer than three times a week. Before recommending
use of laxatives, differential diagnosis should be performed. Prolonged constipation may be evidence of a
significant problem, such as localized peritonitis or
diverticulitis. Complaints of constipation may be
associated with obsessive-compulsive disorder. Use of
laxatives should be avoided in these cases. Patients
should be aware that patterns of defecation are highly
variable, and may vary from two to three times daily to
two to three times weekly.
Laxatives may also be used prophylacticly for
patients, such as those recovering from a myocardial
infarction or those who have had recent surgery, who
should not strain during defecation.
Laxatives are also used to cleanse the lower bowel
before a colonoscopy or similar diagnostic procedure.

Resources

Description

ORGANIZATIONS

American Society for Dermatologic Surgery. 930 N.
Meacham Road, P.O. Box 4014, Schaumburg, IL 601684014. (847) 330-9830. <http://www.asds-net.org>.
American Society for Laser Medicine and Surgery. 2404
Stewart Square, Wausau, WI 54401. (715) 845-9283.
<http://www.aslms.org>.
Cancer Information Service. 9000 Rockville Pike, Building
31, Suite 10A18, Bethesda, MD 20892. 1-800-4CANCER. <http://wwwicic.nci.nih.gov>. 7.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Maureen Haggerty

LASIK see Photorefractive keratectomy
and laser-assisted inLassa fever see Hemorrhagic fevers

Laxatives
Definition
Laxatives are products that promote bowel
movements.

Purpose
Laxatives are used to treat constipation—the
passage of small amounts of hard, dry stools, usually
GALE ENCYCLOPEDIA OF MEDICINE

Laxatives may be grouped by mechanism of
action.
Saline cathartics include dibasic sodium phosphate (Phospo-Soda), magnesium citrate, magnesium hydroxide (milk of magnesia), magnesium
sulfate (Epsom salts), sodium biphosphate, and
others. They act by attracting and holding water in
the intestinal lumen, and may produce a watery stool.
Magnesium sulfate is the most potent of the laxatives
in this group.
Stimulant and irritant laxatives increase the peristaltic movement of the intestine. Examples include
cascara and bisadocyl (Dulcolax.) Castor oil works
in a similar fashion.
Bulk-producing laxatives increase the volume of
the stool, and will both soften the stool and stimulate
intestinal motility. Psyllium (Metamucil, Konsil) and
methylcellulose (Citrucel) are examples of this type.
The overall effect is similar to that of eating high-fiber
foods, and this class of laxative is most suitable for
regular use. Many primary care physicians suggest
that patients try laxatives in this category before
using saline or stimulant laxatives.
Docusate (Colace) is the only representative
example of the stool softener class. It holds water
within the fecal mass, providing a larger, softer stool.
Docusate has no effect on acute constipation, since it
must be present before the fecal mass forms to have
any effect, but may be useful for prevention of constipation in patients with recurrent problems, or those
who are about to take a constipating drug, such as
narcotic analgesics.
2175

Laxatives

Scarring or rupturing of the cornea is uncommon,
but laser surgery on one or both eyes can:

Laxatives

Mineral oil is an emollient laxative. It acts by
retarding intestinal absorption of fecal water, thereby
softening the stool.
The hyperosmotic laxatives are glycerin and lactulose (Chronulac, Duphalac), both of which act by
holding water within the intestine. Lactulose may also
increase peristaltic action of the intestine.
Some newer options for the treatment of chronic
constipation are being developed by various groups of
researchers. These include such alternative therapies
as biofeedback; newer drugs like tegaserod (Zelnorm)
and prucalopride, which stimulate peristalsis; a nerve
growth factor known as neurotrophin-3; and electrical
stimulation of the colon.

Recommended dosage
See specific products.

Precautions
Short-term use of laxatives is generally safe except
in appendicitis, fecal impaction, or intestinal obstruction. Lactulose is composed of two sugar molecules;
galactose and fructose, and should not be administered to patients who require a low galactose diet.
Chronic use of laxatives may result in fluid and
electrolyte imbalances, steatorrhea, osteomalacia,
diarrhea, cathartic colon, and liver disease. Excessive
intake of mineral oil may cause impaired absorption of
oil soluble vitamins, particularly A and D. Excessive
use of magnesium salts may cause hypermanesemia.
Lactulose and magnesium sulfate are pregnancy
category B. Casanthranol, cascara sagrada, danthron,
docusate sodium, docusate calcium, docusate potassium, mineral oil and senna are category C.
Casanthranol, cascara sagrada and danthron are
excreted in breast milk, resulting in a potential
increased incidence of diarrhea in the nursing infant.
The American College of Toxicology states that
cathartics should not be used as a means of clearing
poisons from the digestive tract of a poisoning victim.
Although some physicians have administered these
laxatives along with activated charcoal in order to
reduce the body’s absorption of the poison, this treatment is no longer recommended.

Interactions
Mineral oil and docusate should not be used in
combination. Docusate is an emulsifying agent which
will increase the absorption of mineral oil.
2176

KEY TERMS
Carbohydrates—Compounds, such as cellulose,
sugar, and starch, that contain only carbon, hydrogen, and oxygen, and are a major part of the diets of
people and other animals.
Cathartic colon—A poorly functioning colon,
resulting from the chronic abuse of stimulant
cathartics.
Colon—The large intestine.
Diverticulitis—Inflammation of the part of the
intestine known as the diverticulum.
Fiber—Carbohydrate material in food that cannot
be digested.
Hyperosmotic—Hypertonic, containing a higher
concentration of salts or other dissolved materials
than normal tissues.
Osteomalacia—A disease of adults, characterized
by softening of the bone. Similar to rickets which is
seen in children.
Pregnancy category—A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B:
Animal studies indicate no fetal risk, but no
human studies, or adverse effects in animals, but
not in well-controlled human studies. Category C:
No adequate human or animal studies, or adverse
fetal effects in animal studies, but no available
human data. Category D: Evidence of fetal risk,
but benefits outweigh risks. Category X: Evidence
of fetal risk. Risks outweigh any benefits.
Steatorrhea—An excess of fat in the stool.
Stool—The solid waste that is left after food is
digested. Stool forms in the intestines and passes
out of the body through the anus.

Bisacodyl tablets are enteric coated, and so should
not be used in combination with antacids. The antacids will cause premature rupture of the enteric
coating.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Diarrhea and Constipation.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Society of Health-System Pharmacists (ASHP).
7272 Wisconsin Avenue, Bethesda, MD 20814. (301)
657-3000. <http://www.ashp.org>.
National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570.
nddic@aerie.com. <http://www.niddk.nih.gov/
Brochures/NDDIC.htm>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <http:/www.fda.gov>.

Samuel D. Uretsky, PharmD
Rebecca J. Frey, PhD

Lazy eye see Amblyopia
LCM see Lymphocytic choriomeningitis
LDH isoenzymes test see Lactate
dehydrogenase isoenzymes test
LDH test see Lactate dehydrogenase test

Lead poisoning
Definition
Lead poisoning occurs when a person swallows,
absorbs, or inhales lead in any form. The result can be
damaging to the brain, nerves, and many other parts
of the body. Acute lead poisoning, which is somewhat
rare, occurs when a relatively large amount of lead is
taken into the body over a short period of time. Chronic
lead poisoning—a common problem in children—
occurs when small amounts of lead are taken in over a
longer period. The Centers for Disease Control and
Prevention (CDC) defines childhood lead poisoning
as a whole-blood lead concentration equal to or greater
than 10 micrograms/dL.

mental retardation. At very high levels, lead poisoning
can cause seizures, coma, and even death. According to
the National Center for Environmental Health, there
were about 200 deaths from lead poisoning in the
United States between 1979 and 1998. Most of the
deaths were among males (74%), African Americans
(67%), adults over the age of 45 (76%), and
Southerners (70%).
About one out of every six children in the United
States has a high level of lead in the blood, according to
the Agency for Toxic Substances and Disease Registry.
Many of these children are exposed to lead through
peeling paint in older homes. Others are exposed
through dust or soil that has been contaminated by old
paint or past emissions of leaded gasoline. Since children
between the ages of 12–36 months are apt to put
things in their mouths, they are more likely than older
children to take in lead. Pregnant women who come into
contact with lead can pass it along to the fetus.
Over 80% of American homes built before 1978
have lead-based paint in them, according to the
Centers for Disease Control and Prevention (CDC).
The older the home, the more likely it is to contain lead
paint, and the higher the concentration of lead in the
paint is apt to be. Some homes also have lead in the
water pipes or plumbing. People may have lead in
the paint, dust, or soil around their homes or in their
drinking water without knowing it, since lead can’t be
seen, smelled, or tasted. Because lead doesn’t break
down naturally, it can continue to cause problems
until it is removed.

Causes and symptoms
Before scientists knew how harmful it could be,
lead was widely used in paint, gasoline, water pipes,
and many other products. Today house paint is almost
lead-free, gasoline is unleaded, and household plumbing is no longer made with lead materials. Still, remnants of the old hazards remain. Following are some
sources of lead exposure:


Lead-based paint. This is the most common source of
exposure to large amounts of lead among preschoolers. Children may eat paint chips from older homes
that have fallen into disrepair. They may also chew
on painted surfaces such as windowsills. In addition,
paint may be disturbed during remodeling.



Dust and soil. These can be contaminated with lead
from old paint or past emissions of leaded gasoline.
In addition, pollution from operating or abandoned
industrial sites and smelters can find its way into the
soil, resulting in soil contamination.

Description
Lead can damage almost every system in the
human body, and it can also cause high blood pressure
(hypertension). It is particularly harmful to the developing brain of fetuses and young children. The higher
the level of lead in a child’s blood, and the longer this
elevated level lasts, the greater the chance of ill effects.
Over the long term, lead poisoning in a child can lead
to learning disabilities, behavioral problems, and even
GALE ENCYCLOPEDIA OF MEDICINE

2177

Lead poisoning

Karch, A. M. Lippincott’s Nursing Drug Guide. Springhouse,
PA: Lippincott Williams & Wilkins, 2003.

Lead poisoning



Drinking water. Exposure may come from lead water
pipes, found in many homes built before 1930. Even
newer copper pipes may have lead solder. Also, some
new homes have brass faucets and fittings that can
leach lead.



Jobs and hobbies. A number of activities can expose
participants to lead. These include making pottery or
stained glass, refinishing furniture, doing home
repairs, and using indoor firing ranges. When adults
take part in such activities, they may inadvertently
expose children to lead residue that is on their clothing or on scrap materials.









Food. Imported food cans often have lead solder.
Lead may also be found in leaded crystal glassware
and some imported ceramic or old ceramic dishes
(e.g., ceramic dishes from Mexico). A 2003 study of
cases of lead poisoning in pregnant women found
that 70% of the patients were Hispanics, most of
whom had absorbed the lead from their pottery. In
addition, food may be contaminated by lead in the
water or soil.

It is also known that certain genetic factors
increase the harmful effects of lead poisoning in susceptible children; however, these factors are not completely understood as of 2003.
Lead poisoning is also harmful to adults, in whom
it can cause high blood pressure, digestive problems,
nerve disorders, memory loss, and muscle and joint
pain. In addition, it can lead to difficulties during
pregnancy, as well as cause reproductive problems in
both men and women.
More recently, chronic exposure to lead in the
environment has been found to speed up the progression of kidney disorders in patients without diabetes.
Acute lead poisoning
Acute lead poisoning, while less common, shows
up more quickly and can be fatal. Symptoms such as
the following may occur:


severe abdominal pain



diarrhea



nausea and vomiting



weakness of the limbs



seizures

Moonshine whiskey. Lead poisoning from drinking
illegally distilled liquor is still a cause of death among
adults in the southern United States.



coma

Gunshot wounds. Toxic amounts of lead can be
absorbed from bullets or bullet fragments that
remain in the body after emergency surgery.

A high level of lead in the blood can be detected
with a simple blood test. In fact, testing is the only way
to know for sure if children without symptoms have
been exposed to lead, since they can appear healthy
even as long-term damage occurs. The CDC recommends testing all children at 12 months of age and, if
possible, again at 24 months. Testing should start at
six months for children at risk for lead poisoning.
Based on these test results and a child’s risk factors,
the doctor will then decide whether further testing is
needed and how often. In some states, more frequent
testing is required by law.

Folk medicines. Certain folk medicines (for example,
alarcon, alkohl, azarcon, bali goli, coral, ghasard,
greta, liga, pay-loo-ah, and rueda) and traditional
cosmetics (kohl, for example) contain large amounts
of lead.

Chronic lead poisoning
New evidence suggests that lead may be harmful
to children even at low levels that were once thought to
be safe, and the risk of damage rises as blood levels of
lead increase. The symptoms of chronic lead poisoning
take time to develop, however. Children can appear
healthy despite having high levels of lead in their
blood. Over time, though, problems such as the following may arise:

Diagnosis

Children at risk



learning disabilities



hyperactivity

Children with an increased risk of lead poisoning
include those who:



mental retardation





slowed growth

Live in or regularly visit a house built before 1978 in
which chipped or peeling paint is present.

hearing loss






headaches

Live in or regularly visit a house that was built
before 1978 where remodeling is planned or
underway.

2178

GALE ENCYCLOPEDIA OF MEDICINE

Lead poisoning

Lead in water
Airborne lead

Lead-glazed pottery
Peeling
lead paint

Lead crystal

Peeling
lead paint

Lead
soldered cans
Lead from soil

Lead painted toy

Continuous exposure to lead can damage nearly every system in the human body and is particularly harmful to the developing
brain of fetuses and young children. Common sources of lead exposure include lead-based paint, dust and soil, drinking water,
food from cans, and eating utensils, such as plates and drinking glasses, that are lead-based. (Illustration by Electronic Illustrators
Group.)



Have a brother or sister, housemate, or playmate
who has been diagnosed with lead poisoning.



Have the habit of eating dirt, or have been diagnosed
with pica.





Live with an adult whose job or hobby involves
exposure to lead.
Live near an active lead smelter, battery-recycling
plant, or other industry that can create lead pollution.
Adults at risk

Testing is also important for adults whose job or
hobby puts them at risk for lead poisoning. This
includes people who take part in the following
activities:
GALE ENCYCLOPEDIA OF MEDICINE



glazed pottery or stained glass making



furniture refinishing



home renovation



target shooting at indoor firing ranges



battery reclamation



precious metal refining



radiator repair



art restoration

Treatment
The first step in treating lead poisoning is to avoid
further contact with lead. For adults, this usually
2179

Lead poisoning

means making changes at work or in hobbies. For
children, it means finding and removing sources of
lead in the home. In most states, the public health
department can help assess the home and identify
lead sources.

KEY TERMS
Chelation therapy—Treatment with chemicals that
bind to a poisonous metal and help the body pass it
in urine at a faster rate.
Dimercaprol (BAL)—A chemical agent used to
remove excess lead from the body.

If the problem is lead paint, a professional with
special training should remove it. Removal of lead
paint is not a do-it-yourself project. Scraping or sanding lead paint creates large amounts of dust that can
poison people in the home. This dust can stay around
long after the work is completed. In addition, heating
lead paint can release lead into the air. For these
reasons, lead paint should only be removed by someone who knows how to do the job safely and has the
equipment to clean up thoroughly. Occupants, especially children and pregnant women, should leave the
home until the cleanup is finished.

Edetate calcium disodium (EDTA calcium)—A
chemical agent used to remove excess lead from
the body.
Penicillamine (Cuprimine, Depen)—A drug used
to treat medical problems (such as excess copper in
the body and rheumatoid arthritis) and to prevent
kidney stones. It is also sometimes prescribed to
remove excess lead from the body.
Pica—An abnormal appetite or craving for nonfood items, often such substances as chalk, clay,
dirt, laundry starch, or charcoal.

Medical professionals should take all necessary
steps to remove bullets or bullet fragments from
patients with gunshot injuries.

Succimer (Chemet)—A drug used to remove
excess lead from the body.

Chelation therapy
If blood levels of lead are high enough, the
doctor may also prescribe chelation therapy. This
refers to treatment with chemicals that bind to the
lead and help the body pass it in urine at a faster
rate. There are four chemical agents that may be
used for this purpose, either alone or in combination. Edetate calcium disodium (EDTA calcium)
and dimercaprol (BAL) are given through an intravenous line or in shots, while succimer (Chemet)
and penicillamine (Cuprimine, Depen) are taken
by mouth. (Although many doctors prescribe penicillamine for lead poisoning, this use of the drug
has not been approved by the Food and Drug
Administration.)

Alternative treatment
Changes in diet are no substitute for medical treatment. However, getting enough calcium, zinc, and
protein may help reduce the amount of lead the body
absorbs. Iron is also important, since people who
are deficient in this nutrient absorb more lead. Garlic
and thiamine, a B-complex vitamin, have been used to
treat lead poisoning in animals. However, their usefulness in humans for this purpose has not been proved.
Nutritional, botanical, and homeopathic medicines
can be administered once the source is removed, to
help correct any imbalances brought on by lead
toxicity.
2180

Prognosis
If acute lead poisoning reaches the stage of seizures and coma, there is a high risk of death. Even if
the person survives, there is a good chance of permanent brain damage. The long-term effects of lower
levels of lead can also be permanent and severe.
However, if chronic lead poisoning is caught early,
these negative effects can be limited by reducing future
exposure to lead and getting proper medical
treatment.

Prevention
Many cases of lead poisoning can be prevented.
These steps can help:


Keep the areas where children play as clean and dustfree as possible.



Wash pacifiers and bottles when they fall to the floor,
and wash stuffed animals and toys often.



Make sure children wash their hands before meals
and at bedtime.



Mop floors and wipe windowsills and other chewable
surfaces, such as cribs, twice a week with a solution
of powdered dishwasher detergent in warm water.



Plant bushes next to an older home with painted
exterior walls to keep children at a distance.
GALE ENCYCLOPEDIA OF MEDICINE

Plant grass or another ground cover in soil that is
likely to be contaminated, such as soil around a
home built before 1960 or located near a major
highway.



Have household tap water tested to find out if it
contains lead.



Use only water from the cold-water tap for drinking,
cooking, and making baby formula, since hot water
is likely to contain higher levels of lead.



If the cold water hasn’t been used for six hours or
more, run it for several seconds, until it becomes as
cold as it will get, before using it for drinking or
cooking. The more time water has been sitting in
the pipes, the more lead it may contain.



If you work with lead in your job or hobby, change
your clothes before you go home.



Do not store food in open cans, especially imported
cans.



Do not store or serve food in pottery meant for
decorative use.

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Poisoning: Lead Poisoning.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Gavaghan, Helen. ‘‘Lead, Unsafe at Any Level.’’ Bulletin of
the World Health Organization January 2002: 82.
Kaufmann, R. B., C. J. Staes, and T. D. Matte. ‘‘Deaths
Related to Lead Poisoning in the United States, 19791998.’’ Environmental Research 91 (February 2003):
78–84.
Lanphear, B. P., K. N. Dietrich, and O. Berger. ‘‘Prevention
of Lead Toxicity in US Children.’’ Ambulatory
Pediatrics 3 (January-February 2003): 27–36.
Lidsky, T. I., and J. S. Schneider. ‘‘Lead Neurotoxicity in
Children: Basic Mechanisms and Clinical Correlates.’’
Brain 126, Part 1 (January 2003): 5–19.
Lin, J. L., D. T. Lin-Tan, K. H. Hsu, and C. C. Yu.
‘‘Environmental Lead Exposure and Progression of
Chronic Renal Diseases in Patients Without Diabetes.’’
New England Journal of Medicine 348 (January 23,
2003): 277–286.
‘‘National Campaign to Promote New 24/7 Poison
Hotline.’’ Medical Letter on the CDC & FDA March 10,
2002: 12.
Shannon, M. ‘‘Severe Lead Poisoning in Pregnancy.’’
Ambulatory Pediatrics 3 (January-February 2003):
37–39.
Tarkin, I. S., A. Hatzidakis, S. C. Hoxie, et al. ‘‘Arthroscopic
Treatment of Gunshot Wounds to the Shoulder.’’
Arthroscopy 19 (January 2003): 85–89.
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Tofu May Lower Lead Levels in Blood.’’ Townsend Letter
for Doctors and Patients February-March 2002: 23.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
National Lead Information Center, National Safety
Council. 1025 Connecticut Ave. N.W., Suite 1200,
Washington, DC 20036. (800) 532-3394. <http://
www.nsc.org/ehc/lead.htm>.
Office of Water Resources Center, Environmental
Protection Agency. Mail Code (4100), Room 2615
East Tower Basement, 401 M St. S.W.,
Washington, DC 20460. (800) 426–4791. <http://
www.epa.gov/ow/>.

Linda Wasmer Smith
Rebecca J. Frey, PhD

Learning disorders
Definition
Learning disorders are academic difficulties
experienced by children and adults of average to
above-average intelligence. People with learning disorders have difficulty with reading, writing, mathematics, or a combination of the three. These
difficulties significantly interfere with academic
achievement or daily living.

Description
Learning disorders, or disabilities, affect approximately 2 million children between the ages of six and
17 (5% of public school children), although some
experts think the figure may be as high as 15%.
These children have specific impairments in acquiring,
retaining, and processing information. Standardized
tests place them well below their IQ range in their area
of difficulty. The three main types of learning disorders are reading disorders, mathematics disorders, and
disorders of written expression. The male: female ratio
for learning disorders is about 5:1.
Reading disorders
Reading disorders are the most common type of
learning disorder. Children with reading disorders
have difficulty recognizing and interpreting letters
and words (dyslexia). They aren’t able to recognize
2181

Learning disorders



Learning disorders

and decode the sounds and syllables (phonetic structure) behind written words and language in general.
This condition lowers accuracy and comprehension in
reading.
Mathematics disorders
Children with mathematics disorders (dyscalculia)
have problems recognizing and counting numbers
correctly. They have difficulty using numbers in
everyday settings. Mathematics disorders are typically diagnosed in the first few years of elementary
school when formal teaching of numbers and basic
math concepts begins. Children with mathematics
disorders usually have a co-existing reading disorder,
a disorder of written expression, or both.

KEY TERMS
Dyslexia—An inability to read, write, or spell
words in spite of the ability to see and recognize
letters. Dyslexia is an autosomal dominant disorder
thst occurs more frequently in males.
IQ—Intelligence quotient; a measure of intellectual functioning determined by performance on
standardized intelligence tests.
Phonics—A system to teach reading by teaching
the speech sounds associated with single letters,
letter combinations, and syllables.

Diagnosis
Disorders of written expression
Disorders of written expression typically occur in
combination with reading disorders or mathematics
disorders or both. The condition is characterized by
difficulty with written compositions (dysgraphia).
Children with this type of learning disorder have
problems with spelling, punctuation, grammar, and
organizing their thoughts in writing.

Causes and symptoms
Learning disorders are thought to be caused by
neurological abnormalities that trigger impairments in
the regions of the brain that control visual and language processing and attention and planning. These
traits may be genetically linked. Children from
families with a history of learning disorders are more
likely to develop disorders themselves. In 2003 a team of
Finnish researchers reported finding a candidate gene
for developmental dyslexia on human chromosome
15q21.
Learning difficulties may also be caused by such
medical conditions as a traumatic brain injury or brain
infections such as encephalitis or meningitis.
The defining symptom of a learning disorder is
academic performance that is markedly below a child’s
age and grade capabilities and measured IQ. Children
with a reading disorder may confuse or transpose
words or letters and omit or add syllables to words.
The written homework of children with disorders of
written expression is filled with grammatical, spelling,
punctuation, and organizational errors. The child’s
handwriting is often extremely poor. Children with
mathematical disorders are often unable to count in
the correct sequence, to name numbers, and to understand numerical concepts.
2182

Problems with vision or hearing, mental disorders
(depression, attention-deficit/hyperactivity disorder),
mental retardation, cultural and language differences,
and inadequate teaching may be mistaken for learning
disorders or complicate a diagnosis. A comprehensive
medical, psychological, and educational assessment is
critical to making a clear and correct diagnosis.
A child thought to have a learning disorder should
undergo a complete medical examination to rule out
an organic cause. If none is found, a psychoeducational assessment should be performed by a psychologist, psychiatrist, neurologist, neuropsychologist, or
learning specialist. A complete medical, family, social,
and educational history is compiled from existing
medical and school records and from interviews
with the child and the child’s parents and teachers.
A series of written and verbal tests are then given to
the child to evaluate his or her cognitive and intellectual functioning. Commonly used tests include the
Wechsler Intelligence Scale for Children (WISC-III),
the Woodcock-Johnson Psychoeducational Battery,
the Peabody Individual Achievement Test-Revised
(PIAT-R) and the California Verbal Learning Test
(CVLT). Federal legislation mandates that this testing
is free of charge within the public school system.

Treatment
Once a learning disorder has been diagnosed, an
individual education plan (IEP) is developed for the
child in question. IEPs are based on psychoeducational
test findings. They provide for annual retesting to measure a child’s progress. Learning-disordered students
may receive special instruction within a regular general
education class or they may be taught in a special
education or learning center for a portion of the day.
GALE ENCYCLOPEDIA OF MEDICINE

OTHER

Leeches

Common strategies for the treatment of reading
disorders focus first on improving a child’s recognition
of the sounds of letters and language through phonics
training. Later strategies focus on comprehension,
retention, and study skills. Students with disorders
of written expression are often encouraged to keep
journals and to write with a computer keyboard
instead of a pencil. Instruction for students with
mathematical disorders emphasizes real-world uses
of arithmetic, such as balancing a checkbook or
comparing prices.

LD Online Page. <http://www.ldonline.org>.

Paula Anne Ford-Martin
Rebecca J. Frey, PhD

Leeches
Definition

Prognosis
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, DC: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Learning Disorders.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
PERIODICALS

Galaburda, D. M., and B. C. Duchaine. ‘‘Developmental
Disorders of Vision.’’ Neurologic Clinics 21 (August
2003): 687–707.
Gillberg, C., and H. Soderstrom. ‘‘Learning Disability.’’
Lancet 362 (September 6, 2003): 811–821.
Taipale, M., N. Kaminen, J. Nopola-Hemmi, et al.
‘‘A Candidate Gene for Developmental Dyslexia
Encodes a Nuclear Tetratricopeptide Repeat Domain
Protein Dynamically Regulated in Brain.’’ Proceedings
of the National Academy of Sciences in the USA 100
(September 30, 2003): 11553–11558.
Taylor, K. E., and J. Walter. ‘‘Occupation Choices of Adults
With and Without Symptoms of Dyslexia.’’ Dyslexia 9
(August 2003): 177–185.
Witt, W. P., A. W. Riley, and M. J. Coiro. ‘‘Childhood
Functional Status, Family Stressors, and Psychosocial
Adjustment Among School-Aged Children with
Disabilities in the United States.’’ Archives of Pediatric
and Adolescent Medicine 157 (July 2003): 687–695.

Leeches are bloodsucking worms with segmented
bodies. They belong to the same large classification of
worms as earthworms and certain oceanic worms.
Leeches can primarily be found in freshwater
lakes, ponds, or rivers. They range in size from
0.2 in (5 mm) to nearly 18 in (45 cm) and have two
characteristic suckers located at either end of their
bodies. Leeches consume the blood of a wide variety
of animal hosts, ranging from fish to humans.
To feed, a leech first attaches itself to the host
using the suckers. One of these suckers surrounds
the leech’s mouth, which contains three sets of jaws
that bite into the host’s flesh, making a Y-shaped
incision. As the leech begins to feed, its saliva
releases chemicals that dilate blood vessels, thin
the blood, and deaden the pain of the bite. Because
of the saliva’s effects, a person bitten by a leech may
not even be aware of it until afterwards, when he
or she sees the incision and the trickle of blood that
is difficult to stop.
For centuries, leeches were a common tool of
doctors, who believed that many diseases were the
result of ‘‘imbalances’’ in the body that could be
stabilized by releasing blood. For example, leeches
were sometimes attached to veins in the temples to
treat headaches. Advances in medical knowledge led
doctors to abandon bloodletting and the use of leeches
in the mid-nineteenth century. In recent years, however, doctors have found a new purpose for leeches–
helping to restore blood circulation to grafted or
severely injured tissue.

ORGANIZATIONS

The Interactive Guide to Learning Disabilities for Parents,
Teachers, and Children. <http://www.ldonline.org>.
Learning Disabilities Association of America. 4156 Library
Road, Pittsburg, PA 15234. (412) 341-1515. <http://
www.ldanatl.org>.
National Center for Learning Disabilities (NCLD). 381
Park Avenue South, Suite 1401, New York, NY 10016.
(410) 296-0232. <http://www.ncld.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
There are many occasions in medicine, mostly in
surgery and trauma care, when blood accumulates
and causes trouble. Leeches can be used to reduce
the swelling of any tissue that is holding too much
blood. This problem is most likely to occur in two
situations:
2183

Leeches

KEY TERMS
Anemia—A blood disorder marked by low hemoglobin levels in red blood cells, which leads to a
deficiency of oxygen in the blood.
Anticoagulant—A chemical or medication that
prevents blood from clotting.

These leeches are being used to reduce venous congestion,
or excessive amounts of blood in the blood vessels.
(Photograph by Michael English, M.D., Custom Medical Stock
Photo. Reproduced by permission.)





Trauma. Large blood clots resulting from trauma can
threaten tissue survival by their size and pressure.
Blood clots can also obstruct the patient’s airway.
Surgical procedures involving reattachment of severed body parts or tissue reconstruction following
burns. In these situations it is difficult for the surgeon
to make a route for blood to leave the affected part
and return to the circulation. The hardest part of
reattaching severed extremities like fingers, toes and
ears is to reconnect the tiny veins. If the veins are not
reconnected, blood will accumulate in the injured
area. A similar situation occurs when plastic surgeons
move large flaps of skin to replace skin lost to burns,
trauma or radical surgery. The skin flaps often drain
blood poorly, get congested, and begin to die. Leeches
have come to the rescue in both situations.

Precautions
It is important to use only leeches that have been
raised in the laboratory under sterile conditions in
order to protect patients from infection. Therapeutic
leeches belong to one of two species–Hirudo michaelseni
or Hirudo medicinalis.

and cause tissue death. Leech saliva has been described
as a better anticoagulant than many currently available to treat strokes and heart attacks. Active investigation of the chemicals in leech saliva is currently
under way, and one anticoagulant drug, hirudin, is
derived from the tissues of Hirudo medicinalis.

Aftercare
The leeches are removed by pulling them off or by
loosening their grip with cocaine, heat, or acid. The
used leeches are then killed by placing them in an
alcohol solution and disposed of as a biohazard.
Proper care of the patient’s sore is important, as is
monitoring the rate at which it bleeds after the leech
is removed. Any clots that form at the wound site
during treatment should be removed to ensure effective blood flow.

Risks
Infection is a constant possibility until the sore
heals. It is also necessary to monitor the amount of
blood that the leeches have removed from the patient,
since a drop in red blood cell counts could occur in
rare cases of prolonged bleeding.
Resources
PERIODICALS

Daane, S., et al. ‘‘Clinical Use of Leeches in Reconstructive
Surgery.’’ American Journal of Orthopedics 26, no. 8
(August 1997): 528-532.

J. Ricker Polsdorfer, MD

Description
One or more leeches are applied to the swollen
area, depending on the size of the graft or injury, and
left on for several hours. The benefits of the treatment
lie not in the amount of blood that the leeches ingest,
but in the anti-bloodclotting (anticoagulant) enzymes
in the saliva that allow blood to flow from the bite for
up to six hours after the animal is detached, effectively
draining away blood that could otherwise accumulate
2184

Left ventricular failure see Heart failure
Leg veins x ray see Venography
Legg-Calvé see Osteochondroses
Legionella pneumophila infection see
Legionnaires’ disease
Legionellosis see Legionnaires’ disease
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Legionnaires’ disease is a type of pneumonia caused
by Legionella bacteria. The bacterial species responsible
for Legionnaires’ disease is L. pneumophila. Major
symptoms include fever, chills, muscle aches, and
a cough that is initially nonproductive. Definitive diagnosis relies on specific laboratory tests for the bacteria,
bacterial antigens, or antibodies produced by the body’s
immune system. As with other types of pneumonia,
Legionnaires’ disease poses the greatest threat to people
who are elderly, ill, or immunocompromised.

Description
Legionella bacteria were first identified as a cause
of pneumonia in 1976, following an outbreak of
pneumonia among people who had attended an
American Legion convention in Philadelphia,
Pennsylvania. This eponymous outbreak prompted
further investigation into Legionella and it was
discovered that earlier unexplained pneumonia outbreaks were linked to the bacteria. The earliest cases
of Legionnaires’ disease were shown to have occurred
in 1965, but samples of the bacteria exist from 1947.
Exposure to the Legionella bacteria doesn’t necessarily lead to infection. According to some studies, an
estimated 5-10% of the American population show
serologic evidence of exposure, the majority of whom
do not develop symptoms of an infection. Legionella
bacteria account for 2-15% of the total number of
pneumonia cases requiring hospitalization in the
United States.
There are at least 40 types of Legionella bacteria,
half of which are capable of producing disease in
humans. A disease that arises from infection by
Legionella bacteria is referred to as legionellosis. The
L. pneumophila bacterium, the root cause of
Legionnaires’ disease, causes 90% of legionellosis
cases. The second most common cause of legionellosis
is the L. micdadei bacterium, which produces the
Philadelphia pneumonia-causing agent.
Approximately 10,000-40,000 people in the
United States develop Legionnaires’ disease annually.
The people who are the most likely to become ill are
over age 50. The risk is greater for people who suffer
from health conditions such as malignancy, diabetes,
lung disease, or kidney disease. Other risk factors
include immunosuppressive therapy and cigarette
smoking. Legionnaires’ disease has occurred in children, but typically it has been confined to newborns
GALE ENCYCLOPEDIA OF MEDICINE

Cases of Legionnaires’ disease that occur in
conjunction with an outbreak, or epidemic, are more
likely to be diagnosed quickly. Early diagnosis aids
effective and successful treatment. During epidemic
outbreaks, fatalities have ranged from 5% for
previously healthy individuals to 24% for individuals
with underlying illnesses. Sporadic cases (that is, cases
unrelated to a wider outbreak) are harder to detect
and treatment may be delayed pending an accurate
diagnosis. The overall fatality rate for sporadic cases
ranges from 10-19%. The outlook is bleaker in severe
cases that require respiratory support or dialysis.
In such cases, fatality may reach 67%.

Causes and symptoms
Legionnaires’ disease is caused by inhaling
Legionella bacteria from the environment. Typically,
the bacteria are dispersed in aerosols of contaminated
water. These aerosols are produced by devices in which
warm water can stagnate, such as air-conditioning
cooling towers, humidifiers, shower heads, and faucets.
There have also been cases linked to whirlpool spa
baths and water misters in grocery store produce
departments. Aspiration of contaminated water is
also a potential source of infection, particularly in
hospital-acquired cases of Legionnaires’ disease. There
is no evidence of person-to-person transmission of
Legionnaires’ disease.
Once the bacteria are in the lungs, cellular representatives of the body’s immune system (alveolar
macrophages) congregate to destroy the invaders.
The typical macrophage defense is to phagocytose
the invader and demolish it in a process analogous to
swallowing and digesting it. However, the Legionella
bacteria survive being phagocytosed. Instead of being
destroyed within the macrophage, they grow and
replicate, eventually killing the macrophage. When
the macrophage dies, many new Legionella bacteria
are released into the lungs and worsen the infection.
Legionnaires’ disease develops 2-10 days after
exposure to the bacteria. Early symptoms include
lethargy, headaches, fever, chills, muscle aches, and a
lack of appetite. Respiratory symptoms such as
coughing or congestion are usually absent. As the
disease progresses, a dry, hacking cough develops
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Legionnaires’ disease

Legionnaires’ disease

receiving respiratory therapy, children who have had
recent operations, and children who are immunosuppressed. People with HIV infection and AIDS do not
seem to contract Legionnaires’ disease with any
greater frequency than the rest of the population,
however, if contracted, the disease is likely to be
more severe compared to other cases.

Legionnaires’ disease

vomiting, and an initially dry cough, laboratory tests
are done to definitively identify L. pneumophila as the
cause of the infection.

A transmission electron microscopy (TEM) image of Legionella
pneumophila, the bacteria which causes Legionnaires’ disease. (Custom Medical Stock Photo. Reproduced by permission.)

and may become productive after a few days. In about
a third of Legionnaires’ disease cases, blood is present
in the sputum. Half of the people who develop
Legionnaires’ disease suffer shortness of breath and
a third complain of breathing-related chest pain. The
fever can become quite high, reaching 104 8F (40 8C) in
many cases, and may be accompanied by a decreased
heart rate.
Although the pneumonia affects the lungs,
Legionnaires’ disease is accompanied by symptoms
that affect other areas of the body. About half the
victims experience diarrhea and a quarter have nausea
and vomiting and abdominal pain. In about 10% of
cases, acute renal failure and scanty urine production
accompany the disease. Changes in mental status, such
as disorientation, confusion, and hallucinations, also
occur in about a quarter of cases.
In addition to Legionnaires’ disease, L. pneumophila
legionellosis also includes a milder disease, Pontiac fever.
Unlike Legionnaires’ disease, Pontiac fever does not
involve the lower respiratory tract. The symptoms
usually appear within 36 hours of exposure and include
fever, headache, muscle aches, and lethargy. Symptoms
last only a few days and medical intervention is not
necessary.

Diagnosis
The symptoms of Legionnaires’ disease are common to many types of pneumonia and diagnosis of
sporadic cases can be difficult. The symptoms and
chest x rays that confirm a case of pneumonia are
not useful in differentiating between Legionnaires’
disease and other pneumonias. If a pneumonia case
involves multisystem symptoms, such as diarrhea and
2186

If Legionnaires’ disease is suspected, several tests
are available to reveal or indicate the presence of
L. pneumophila bacteria in the body. Since the immune
system creates antibodies against infectious agents,
examining the blood for these indicators is a key test.
The level of immunoglobulins, or antibody molecules,
in the blood reveals the presence of infection. In microscopic examination of the patient’s sputum, a fluorescent stain linked to antibodies against L. pneumophila
can uncover the presence of the bacteria. Other means
of revealing the bacteria’s presence from patient
sputum samples include isolation of the organism on
culture media or detection of the bacteria by DNA
probe. Another test detects L. pneumophila antigens in
the urine.

Treatment
Most cases of Legionella pneumonia show
improvement within 12-48 hours of starting antibiotic therapy. The antibiotic of choice has been erythromycin, sometimes paired with a second antibiotic,
rifampin. Tetracycline, alone or with rifampin, is
also used to treat Legionnaires’ disease, but has had
more mixed success in comparison to erythromycin.
Other antibiotics that have been used successfully to
combat Legionella include doxycycline, clarithromycin, fluorinated quinolones, and trimethoprim/
sulfamethoxazole.
The type of antibiotic prescribed by the doctor
depends on several factors including the severity of
infection, potential allergies, and interaction with previously prescribed drugs. For example, erythromycin
interacts with warfarin, a blood thinner. Several drugs,
such as penicillins and cephalosporins, are ineffective
against the infection. Although they may be deadly
to the bacteria in laboratory tests, their chemical
structure prevents them from being absorbed into the
areas of the lung where the bacteria are present.
In severe cases with complications, antibiotic
therapy may be joined by respiratory support. If
renal failure occurs, dialysis is required until renal
function is recovered.

Prognosis
Appropriate medical treatment has a major
impact on recovery from Legionnaires’ disease.
Outcome is also linked to the victim’s general health
and absence of complications. If the patient survives
GALE ENCYCLOPEDIA OF MEDICINE

Antibody—A molecule created by the immune
system in response to the presence of an antigen.
It serves to recognize the invader and help defend
the body from infection.
Antigen—A molecule, such as a protein, which is
associated with a particular infectious agent. The
immune system uses this molecule as the identifying characteristic of the infectious invader.
Culture—A laboratory system for growing bacteria
for further study.
DNA probe—An agent that binds directly to a predefined sequence of nucleic acids.
Immunocompromised—Refers to conditions in
which the immune system is not functioning properly and cannot adequately protect the body from
infection.
Immunoglobulin—The protein molecule that
serves as the primary building block of antibodies.
Immunosuppressive therapy—Medical treatment
in which the immune system is purposefully
thwarted. Such treatment is necessary, for example,
to prevent organ rejection in transplant cases.
Legionellosis—A disease caused by infection with
a Legionella bacterium.
Media—Substance which contains all the nutrients
necessary for bacteria to grow in a culture.
Phagocytosis—The ‘‘ingestion’’ of a piece of matter
by a cell.

the infection, recovery from Legionnaires’ disease is
complete. Similar to other types of pneumonia, severe
cases of Legionnaires’ disease may cause scarring in
the lung tissue as a result of the infection. Renal failure, if it occurs, is reversible and renal function returns
as the patient’s health improves. Occasionally, fatigue
and weakness may linger for several months after the
infection has been successfully treated.

Prevention
Since the bacteria thrive in warm stagnant water,
regularly disinfecting ductwork, pipes, and other areas
that may serve as breeding areas is the best method for
preventing outbreaks of Legionnaires’ disease. Most
outbreaks of Legionnaires’ disease can be traced to
specific points of exposure, such as hospitals, hotels,
and other places where people gather. Sporadic cases
GALE ENCYCLOPEDIA OF MEDICINE

are harder to determine and there is insufficient
evidence to point to exposure in individual homes.
Resources
PERIODICALS

Shuman, H. A., et al. ‘‘Intracellular Multiplication of
Legionella pneumophila: Human Pathogen of
Accidental Tourist?’’ Current Topics in Microbiology
and Immunology 225 (1998): 99.

Julia Barrett

Leiomyomas see Uterine fibroids

Leishmaniasis
Definition
Leishmaniasis refers to several different illnesses
caused by infection with an organism called a
protozoan.

Description
Protozoa are considered to be the most simple
organisms in the animal kingdom. They are all singlecelled. The types of protozoa that cause leishmaniasis
are carried by the blood-sucking sandfly. The sandfly is
referred to as the disease vector, simply meaning that
the infectious agent (the protozoan) is carried by the
sandfly and passed on to other animals or humans in
whom the protozoan will set up residence and cause
disease. The animal or human in which the protozoan
then resides is referred to as the host.
Once the protozoan is within the human host,
the human’s immune system is activated to try to
combat the invader. Specialized immune cells called
macrophages work to swallow up the protozoa.
Usually, this technique kills a foreign invader, but
these protozoa can survive and flourish within macrophages. The protozoa multiply within the macrophages, ultimately causing the macrophage to burst
open. The protozoa are released, and take up residence
within other neighboring cells.
At this point, the course of the disease caused
by the protozoa is dependent on the specific type of
protozoa, and on the type of reaction the protozoa
elicits from the immune system. There are several
types of protozoa that cause leishmaniasis, and they
cause different patterns of disease progression.
2187

Leishmaniasis

KEY TERMS

Leishmaniasis

At any one time, about 20 million people throughout the world are infected with leishmaniasis. Between
one million and one and one-half million cases of cutaenous leishmaniasis are reported yearly worldwide.
While leishmaniasis exists as a disease in 88 countries
on five continents, some countries are hit harder than
others. These include Bangladesh, India, Nepal, Sudan,
Afghanistan, Brazil, Iran, Peru, Saudi Arabia, and
Syria. Other areas that harbor the causative protozoa
include China, many countries throughout Africa,
Mexico, Central and South America, Turkey, and
Greece. Although less frequent, cases have occurred in
the United States, in Texas.
As Americans travel to these countries, they will
come in contact the protozoa that cause forms of
leishmaniasis. Also, physicians were advised in 2004 to
suspect cutaneous leishmaniasis in military personnel
who were deployed to areas where the infection is
present. From August 2002 to February 2004, staff
from the U.S. Department of Defense identified 522
confirmed cases of the disease in American military
personnel.
In some areas of southern Europe, leishmaniasis
is becoming an important disease that infects people
with weakened immune systems. In particular, individuals with acquired immunodeficiency syndrome
(AIDS) are at great risk of this infection.

Causes and symptoms
There are a number of types of protozoa that can
cause leishmaniasis. Each type exists in specific locations,
and there are different patterns to the kind of disease
each causes. The overall species name is Leishmania
(commonly abbreviated L.). The specific types include:
L. Donovani, L. Infantum, L. Chagasi, L. Mexicana, L.
Amazonensis, L. Tropica, L. Major, L. Aethiopica,
L. Brasiliensis, L. Guyaensis, L. Panamensis, L.
Peruviana. Some of the names are reflective of the
locale in which the specific protozoa is most commonly
found, or in which it was first discovered.
Localized cutaneous leishmaniasis
This type of disease occurs most commonly in
China, India, Asia Minor, Africa, the Mediterranean
Basin, and Central America. It has occurred in an area
ranging from northern Argentina all the way up to
southern Texas. It is called different names in different
locations, including chiclero ulcer, bush yaws, uta,
oriental sore, Aleppo boil, and Baghdad sore.
This is perhaps the least drastic type of disease
caused by any of the Leishmania. Several weeks or
2188

months after being bitten by an infected sandfly, the
host may notice an itchy bump (lesion) on an arm, leg,
or face. Lymph nodes in the area of this bump may
be swollen. Within several months, the bump develops
a crater (ulceration) in the center, with a raised,
reddened ridge around it. There may be several of
these lesions near each other, and they may spread
into each other to form one large lesion. Although
localized cutaneous leishmaniasis usually heals on its
own, it may take as long as one year. A depressed,
light-colored scar usually remains behind. Some
lesions never heal, and may invade and destroy the
tissue below. For example, lesions on the ears may
slowly, but surely, invade and destroy the cartilage
that supports the outer ear.
Diffuse cutaneous leishmaniasis
This type of disease occurs most often in Ethiopia,
Brazil, Dominican Republic, and Venezuela.
The lesions of diffuse cutaneous leishmaniasis
are very similar to those of localized cutaneous leishmaniasis, except they are spread all over the body.
The body’s immune system apparently fails to battle
the protozoa, which are free to spread throughout.
The characteristic lesions resemble those of the dread
biblical disease, leprosy.
Mucocutaneous leishmaniasis
This form of leishmaniasis occurs primarily in the
tropics of South America. The disease begins with the
same sores noted in localized cutaneous leishmaniasis.
Sometimes these primary lesions heal, other times they
spread and become larger. Some years after the first
lesion is noted (and sometimes several years after that
lesion has totally healed), new lesions appear in the
mouth and nose, and occasionally in the area between
the genitalia and the anus (the perineum). These new
lesions are particularly destructive and painful. They
erode underlying tissue and cartilage, frequently eating through the septum (the cartilage that separates
the two nostrils). If the lesions spread to the roof of
the mouth and the larynx (the part of the wind pipe
which contains the vocal cords), they may prevent
speech. Other symptoms include fever, weight loss,
and anemia (low red blood cell count). There is
always a large danger of bacteria infecting the
already open sores.
Visceral leishmaniasis
This type of leishmaniasis occurs inIndia, China,
the southern region of Russia, and throughout Africa,
GALE ENCYCLOPEDIA OF MEDICINE

Treatment

This condition, also called an oriental sore, is caused by the
bacterium L. tropica. (Photograph by Lester V. Bergman, Corbis
Images. Reproduced by permission.)

the Mediterranean, and South and Central America.
It /is frequently called Kala-Azar or Dumdum fever.
In this disease, the protozoa use the bloodstream
to travel to the liver, spleen, lymph nodes, and bone
marrow. Fever may last for as long as eight weeks,
disappear, and then reappear again. The lymph nodes,
spleen, and liver are often quite enlarged. Weakness,
fatigue, loss of appetite, diarrhea, and weight loss are
common. Kala-azar translates to mean ‘‘black fever.’’
The name kala-azar comes from a characteristic of this
form of leishmaniasis. Individuals with light-colored
skin take on a darker, grayish skin tone, particularly of
their face and hands. A variety of lesions appear on
the skin.

Diagnosis
Diagnosis for each of these types of leishmaniasis
involves taking a scraping from a lesion, preparing it
in a laboratory, and examining it under a microscope
to demonstrate the causative protozoan. Other methods that have been used include culturing a sample
piece of tissue in a laboratory to allow the protozoa to
multiply for easier microscopic identification; injecting a mouse or hamster with a solution made of scrapings from a patient’s lesion to see if the animal
develops a leishmaniasis-like disease; and demonstrating the presence in macrophages of the characteristicappearing protozoan, called Leishman-Donovan
bodies.
In some forms of leishmaniasis, a skin test (similar
to that given for TB) may be used. In this test, a
solution containing a small bit of the protozoan
GALE ENCYCLOPEDIA OF MEDICINE

The treatment of choice for all forms of leishmaniasis is a type of drug containing the element
antimony. These include sodium sitogluconate, and
meglumin antimonate. When these types of drugs
do not work, other medications with anti-protozoal
activity are utilized, including amphotericin B,
pentamidine, flagyl, and allopurinol. In 2004, it
was reported that the world’s first non-profit drug
company was seeking approval in India for a drug
to cure visceral leishmaniasis. An estimated
200,000 people die annually from the disease in
that country. The company, called OneWorld
Health, hoped to offer the drug called paromomycin
for a day for a three-week treatment course.

Prognosis
The prognosis for leishmaniasis is quite variable,
and depends on the specific strain of infecting protozoan, as well as the individual patient’s immune
system response to infection. Localized cutaneous
leishmaniasis may require no treatment. Although it
may take many months, these lesions usually heal
themselves completely. Only rarely do these lesions
fail to heal and become more destructive.
Disseminated cutaneous leishmaniasis may
smolder on for years without treatment, ultimately
causing death when the large, open lesions become
infected with bacteria.
Mucocutaneous leishmaniasis is often relatively
resistant to treatment. Untreated visceral leishmaniasis
has a 90% death rate, but only a 10% death rate with
treatment.

Prevention
Prevention involves protecting against sandfly
bites. Insect repellents used around homes, on clothing,
on skin, and on bednets (to protect people while
sleeping) are effective measures.
Reducing the population of sandflies is also an
important preventive measure. In areas where leishmaniasis is very common, recommendations include
clearing the land of trees and brush for at least 984 ft
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Leishmaniasis

antigen (cell marker that causes the human immune
system to react) is injected or scratched into a patient’s
skin. In a positive reaction, cells from the immune
system will race to this spot, causing a characteristic
skin lesion. Not all forms of leishmaniasis cause a
positive skin test, however.

Leprosy

KEY TERMS
Host—The organism (such as a monkey or human)
in which another organism (such as a virus or
bacteria) is living.
Larynx—The part of the airway lying between the
pharynx and the trachea.
Leishman-Donovan body—A body of a (trypanosomatid) protozoa at a particular and characteristic
stage in its life cycle; the infectious (trypanosomatid)
protozoa can cause leishmaniasis, and is relatively
easy to identify at that stage.
Lesion—A disruption of the normal structure and
function of a tissue by some disease process.
Macrophage—A cell of the immune system that
engulfs and digests foreign invaders such as bacteria
and viruses in an attempt to stop them from causing
disease within the body.
Protozoa—A group of organisms which are the
smallest members of the animal kingdom, consisting of a single cell.
Ulceration—An area of pitting and irritation.
Vector—A carrier organism (such as a fly or mosquito) that to delivers a virus (or other agent of
infection) to a host.

(300 m) around all villages, and regularly spraying
the area with insecticides. Because rodents often
carry the protozoan that causes leishmaniasis, careful rodent control should be practiced. Dogs, which
also carry the protozoan, can be given a simple
blood test.
Resources
PERIODICALS

MacReady, Norma. ‘‘Leishmaniasis Hits Military Hot
Spots.’’ Internal Medicine News June 15, 2004: 58.
‘‘Seeking First-time Approval.’’ Chemist & Druggist May 8,
2004: 12.
‘‘Treatment of Cutaneous Leishmaniasis Among Travelers
Reviewed.’’ Vaccine Weekly April 28, 2004: 58.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD
Teresa G. Odle
2190

Leprosy
Definition
Leprosy is a slowly progressing bacterial infection
that affects the skin, peripheral nerves in the hands
and feet, and mucous membranes of the nose, throat,
and eyes. Destruction of the nerve endings causes the
the affected areas to lose sensation. Occasionally,
because of the loss of feeling, the fingers and toes
become mutilated and fall off, causing the deformities
that are typically associated with the disease.

Description
Leprosy is also known as Hansen’s disease after
G. A. Hansen, who in 1878 identified the bacillus
Mycobacterium leprae that causes the disease.
The infection is characterized by abnormal
changes of the skin. These changes, called lesions, are
at first flat and red. Upon enlarging, they have irregular shapes and a characteristic appearance. The lesions
are typically darker in color around the edges with
discolored pale centers. Because the organism grows
best at lower temperatures the leprosy bacillus has a
preference for the skin, the mucous membranes and
the nerves. Infection in and destruction of the nerves
leads to sensory loss. The loss of sensation in the
fingers and toes increases the risk of injury.
Inadequate care causes infection of open wounds.
Gangrene may also follow, causing body tissue to die
and become deformed.
Because of the disabling deformities associated
with it, leprosy has been considered one of the most
dreaded diseases since biblical times, though much of
what was called leprosy in the Old Testament most
likely was not the same disease. Its victims were often
shunned by the community, kept at arm’s length, or
sent to a leper colony. Many people still have misconceptions about the disease. Contrary to popular belief,
it is not highly communicable and is extremely slow to
develop. Household contacts of most cases and the
medical personnel caring for Hansen’s disease patients
are not at particular risk. It is very curable, although the
treatment is long-term, requiring multiple medications.
The World Health Organization (WHO) puts the
number of identified leprosy cases in the world at
about 600,000 as of the early 2000s. Seventy percent
of all cases are found in just three countries: India,
Indonesia, and Myanamar (Burma). The infection can
be acquired, however, in the Western Hemisphere as
well. There are about 5000 reported cases in the
United States as of 2004, almost all of which involve
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The organism that causes leprosy is a rod-shaped
bacterium called Mycobacterium leprae. This bacterium
is related to Mycobacterium tuberculosis, the causative
agent of tuberculosis. Because special staining techniques involving acids are required to view these bacteria
under the microscope, they are referred to as acid-fast
bacilli (AFB).
When Mycobacterium leprae invades the body,
one of two reactions can take place. In tuberculoid
leprosy (TT), the milder form of the disease, the body’s
immune cells attempt to seal off the infection from
the rest of the body by surrounding the offending
pathogen. Because this response by the immune system occurs in the deeper layers of the skin, the hair
follicles, sweat glands, and nerves can be destroyed. As
a result, the skin becomes dry and discolored and loses
its sensitivity. Involvement of nerves on the face, arms,
or legs can cause them to enlarge and become easily
felt by the doctor. This finding is highly suggestive of
TT. The scarcity of bacteria in this type of leprosy
leads to it being referred to as paucibacillary (PB)
leprosy. Seventy to eighty percent of all leprosy cases
are of the tuberculoid type.
In lepromatous (LL) leprosy, which is the second
and more contagious form of the disease, the body’s
immune system is unable to mount a strong response
to the invading organism. Hence, the organism
multiplies freely in the skin. This type of leprosy is
also called the multibacillary (MB) leprosy, because
of the presence of large numbers of bacteria. The
characteristic feature of this disease is the appearance
of large nodules or lesions all over the body and face.
Occasionally, the mucous membranes of the eyes,
nose, and throat may be involved. Facial involvement
can produce a lion-like appearance (leonine facies).
This type of leprosy can lead to blindness, drastic
change in voice, or mutilation of the nose. Leprosy
can strike anyone; however, children seem to be more
susceptible than adults.
Well-defined skin lesions that are numb are the
first symptoms of tuberculoid leprosy. Lepromatous
leprosy is characterized by a chronic stuffy nose due to
invasion of the mucous membranes, and the presence
of nodules and lesions all over the body and face.
GALE ENCYCLOPEDIA OF MEDICINE

Although patients with leprosy are commonly
thought not to suffer pain, neuroapthic pain caused
by inflammation of peripheral nerve endings is
increasingly recognized as a major complication of
the disease in many patients. Corticosteroids may be
given to reduce the inflammation.
The incubation period of the leprosy bacillus
varies anywhere from six months to ten years. On an
average, it takes four years for the symptoms of tuberculoid leprosy to develop. Probably because of the
slow growth of the bacillus, lepromatous leprosy
develops even more slowly, taking an average of
eight years for the initial lesions to appear.
It is still not very clear how the leprosy bacillus is
transmitted from person to person; about 50% of
patients diagnosed with the disease have a history of
close contact with an infected family member. Since
untreated patients have a large number of M. leprae
bacilli in their nasal secretions, it is thought that
transmission may take place via nasal droplets. The
milder tubercular form of leprosy may be transmitted
by insect carriers or by contact with infected soil.
The incidence of leprosy is highest in the poverty
belt of the globe. Therefore, environmental factors
such as unhygienic living conditions, overpopulation,
and malnutrition may also be contributing factors
favoring the infection.
It is also possible that genetic factors are involved
in susceptibility to leprosy. In 2003, scientists conducting a genome scan of a large Vietnamese family with
many cases of leprosy found that susceptibility to the
disease was linked to region q25 on the long arm of
chromosome 6. Further study indicated that the
leprosy susceptibility gene lies within a region shared
by two genes for Parkinson’s disease. Further research
may confirm that the emergence of leprosy in certain
individuals is related to inheritance of genes for
Parkinson’s disease.

Diagnosis
One of the hallmarks of leprosy is the presence of
AFB in smears taken from the skin lesions, nasal
scrapings, or tissue secretions. In patients with LL
leprosy, the bacilli are easily detected; however, in
TT leprosy the bacteria are very few and almost
impossible to find. In such cases, a diagnosis is made
based on the clinical signs and symptoms, the type and
distribution of skin lesions, and history of having lived
in an endemic area.
The signs and symptoms characteristic of leprosy
can be easily identified by a health worker after a short
2191

Leprosy

immigrants from developing countries. Cases also
occur in some areas of the Caribbean. Although it
was thought for many years that only humans are
affected by the disease, 15% of wild armadillos in
southern Texas and Louisiana have been found to be
infected with M. leprae.

Leprosy

Each of the drugs has minor side effects. Dapsone
can cause nausea, dizziness, palpitations, jaundice and
rash. A doctor should be contacted immediately if a
rash develops. Dapsone also interacts with the second
drug, rifampin. Rifampin increases the metabolizing
of dapsone in the body, requiring an adjustment of the
dapsone dosage. rifampin may also cause muscle
cramps, or nausea. If jaundice, flu-like symptoms or
a rash appear, a doctor should be contacted immediately. The third drug, clofazimine may cause severe
abdominal pain and diarrhea, as well as discoloration
of the skin. Red to brownish black discoloration of the
skin and bodily fluids, including sweat, may persist for
months to years after use.
Thalidomide, the most famous agent of birth
defects in the twentieth century, is now being used to
treat complications of leprosy and similar diseases.
Thalidomide regulates the immune response by suppressing a protein, tumor necrosis factor alpha.
Lesions such as these are characteristic of leprosy.
(Phototake NYC. Reproduced by permission.)

training period. There is no need for a laboratory
investigation to confirm a leprosy diagnosis, except
in very rare circumstances.
In an endemic area, if smears from an individual
show the presence of AFB, or if he has typical skin
lesions, he should definitely be regarded as having
leprosy. Usually, there is slight discoloration of the
skin and loss of skin sensitivity. Thickened nerves
accompanied by weakness of muscles supplied by the
affected nerve are very typical of the disease. One
characteristic occurrence is a foot drop where the
foot cannot be flexed upwards, affecting the ability
to walk.

Treatment
The most widely used drug for leprosy is dapsone
(DDS). However, the emergence of dapsone-resistant
strains prompted the introduction of multidrug
therapy, or MDT. MDT combines dapsone, rifampin
(Rifadin; also known as rifampicin), and clofazimine
(Lamprene), all of which are powerful antibacterial
drugs. Patients with MB leprosy are usually treated
with all three drugs, while patients with PB leprosy
are only given rifampin and dapsone. Usually three
months after starting treatment, a patient ceases being
infectious, though not everyone with this disease is
necessarily infectious before treatment. Depending
on the type of leprosy, the time required for treatment
may vary from six months to two years or more.
2192

Leprosy patients should be aware that treatment
itself can cause a potentially serious immune system
response called a lepra reaction. When antibiotics
kill M. leprae, antigens (the proteins on the surface of
the organism that initiate the body’s immune system
response) are released from the dying bacteria. In some
people, when the antigens combine with the antibodies
to M. Leprae in the bloodstream, a reaction called
erythema nodosum leprosum may occur, resulting in
new lesions and peripheral nerve damage. Cortisonetype medications and, increasingly, thalidomide are
used to minimize the effects of lepra reactions.
In some cases, severe ulcers caused by leprosy may
be treated surgically with small skin grafts.

Prognosis
Leprosy is curable; however, the deformities
and nerve damage associated with leprosy are often
irreversible. Preventions or rehabilition of these
defects is an integral part of management of the
disease. Reconstructive surgery, aimed at preventing
and correcting deformities, offers the greatest hope
for disabled patients. Sometimes, the deformities are
such that the patients will not benefit from this type
of surgery.
Comprehensive care involves teaching patients to
care for themselves. If the patients have significant
nerve damage or are at high risk of developing
deformities, they must be taught to take care of their
insensitive limbs, similar to diabetics with lower leg
nerve damage. Lacking the sensation of pain in many
cases, the patients should constantly check themselves
GALE ENCYCLOPEDIA OF MEDICINE

Endemic area—A geographical area where a particular disease is prevalent.
Gangrene—Death of tissue due to loss of blood
supply followed by bacterial invasion and
putrefaction.

Some physicians have advocated dapsone treatment
for people in close household contact with leprosy
patients.

Incubation period—The time it takes for symptoms
to develop after initial exposure to a diseasecausing organism.

The WHO Action Program for the Elimination of
Leprosy adopted a resolution calling for the elimination of leprosy around the world by the year 2005. This
goal is not likely to be reached, however; a computer
simulation performed for WHO by a team of Dutch
researchers in 2004 indicates that leprosy is likely to
persist in some parts of the world until 2020, although
its incidence will continue to decline.

Lesion—Any visible, local abnormality of the tissues
of the skin, such as a wound, sore, rash, or boil.

Resources

Mucous membranes—The inner tissue that covers
or lines body cavities or canals open to the outside,
such as nose and mouth. These membranes secrete
mucus and absorb water and salts.
Nasal scraping—Pathological material obtained
for clinical study by scratching the inner surface
of the nose with a clinical instrument.
Nodules—A small mass of tissue in the form of a
protuberance or a knot that is solid and can be
detected by touch.
Pathogen—Any disease-producing agent or
microorganism.
Smear—A specimen prepared for microscopic
study by spreading the material across a slide and
treating it with a specific stain.

to identify cuts and bruises. If adequate care is not
taken, these wounds become festering sores and a
source of dangerous infection. Physiotherapy exercises are taught to the patients to maintain a range of
movement in finger joints and prevent the deformities
from worsening. Prefabricated standardized splints
are available and are extremely effective in correcting
and preventing certain common deformities in
leprosy. Special kinds of footwear have been designed
for patients with insensitive feet in order to prevent or
minimize the progression of foot ulcers.

Prevention
By early diagnosis and appropriate treatment of
infected individuals, even a disease as ancient as
leprosy can be controlled. People who are in immediate contact with the leprosy patient should be tested
for leprosy. Annual examinations should also be
conducted on these people for a period of five years
following their last contact with an infectious patient.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Infectious Diseases Caused by Mycobacteria.’’ In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Buschman, E., and E. Skamene. ‘‘Linkage of Leprosy
Susceptibility to Parkinson’s Disease Genes.’’
International Journal of Leprosy and Other
Mycobacterial Diseases 72 (June 2004): 169–170.
Jayaseelan, A., and W. Aithal. ‘‘Pinch Skin Grafting in
Non-Healing Leprous Ulcers.’’ International Journal
of Leprosy and Other Mycobacterial Diseases 72
(June 2004): 139–142.
Meima, A., W. C. Smith, G. J. van Oortmarssen, et al.
‘‘The Future Incidence of Leprosy: A Scenario
Analysis.’’ Bulletin of the World Health Organization 82
(May 2004): 373–380.
Stump, P. R., R. Baccarelli, L. H. Marciano, et al.
‘‘Neuropathic Pain in Leprosy Patients.’’ International
Journal of Leprosy and Other Mycobacterial Diseases 72
(June 2004): 134–148.
ORGANIZATIONS

American Leprosy Missions. 1 ALM Way, Greenville, SC
29601. (1-800-LEPROSY).
British Leprosy Relief Association, LEPRA. Fairfax House,
Causton Road, Colchester, Essex CO1 1PU, UK.
INFOLEP, Leprosy Information Services. Postbus
95005,1090 HA, Amsterdam, Netherlands.
Infolep@antenna.nl.
WHO/LEP, Action Programme for the Elimination of
Leprosy. 20 Avenue Appia CH-1211, Geneva 27,
Suisse. <http://www.who.ch/programmes/lep/
lep_home.htm>.
OTHER

Cherath, Lata. ‘‘Leprosy.’’ A Healthy Me Page. <http://
www.ahealthyme.com/topic/topic100587076>.

Lata Cherath, PhD
Rebecca J. Frey, PhD
2193

Leprosy

KEY TERMS

Leptospirosis

Leptospirosis
Definition
Leptospirosis is a febrile disease (fever) caused by
infection with the bacterium Leptospira interrogans.
L. interrogans is sometimes classified as a spirochete
because it has a spiral shape. The disease can range
from very mild and symptomless to a more serious,
even life threatening form, that may be associated with
kidney (renal) failure.

Description
An infection by the bacterium Leptospira interrogans goes by different names in different regions.
Alternate names for leptospirosis include mud fever,
swamp fever, cane cutter’s fever, rice field fever,
Stuttgart disease, swineherd’s disease, and Fort Bragg
fever. More severe cases of leptospirosis are called
Weil’s syndrome or icterohemorrhagic fever. This disease is commonly found in tropical and subtropical
climates but occurs worldwide.
According to the Centers for Disease Control and
Prevention (CDC), between 100 and 200 cases of
leptospirosis are reported in the United States each
year as of the early 2000s. Almost 75% of cases of
leptospirosis in North America occur in males. About
50% of these cases occur in Hawaii, followed by the
southern Atlantic, Gulf, and Pacific coastal states.
However, because of the nonspecific symptoms of
leptospirosis, it is believed that the occurrence in the
United States is actually much higher. Leptospirosis
occurs year-round in North America, but about half
of the cases occur between July and October.
Leptospirosis is called a zoonosis because it is a
disease of animals that can be transmitted to humans.
It can be a very serious problem in the livestock industry. Leptospira bacteria have been found in dogs, rats,
livestock, mice, voles, rabbits, hedgehogs, skunks,
possums, frogs, fish, snakes, and certain birds and
insects. Infected animals will pass the bacteria in
their urine for months, or even years. In the United
States, rats and dogs are more commonly linked with
human leptospirosis than other animals.
Humans are considered accidental hosts and
become infected with Leptospira interrogans by coming into contact with urine from infected animals.
Transmission of the organism occurs either through
direct contact with urine, or through contact with
soil, water, or plants that have been contaminated by
animal urine. Leptospira interrogans can survive for
2194

as long as six months outdoors under favorable
conditions. Leptospira bacteria can enter the body
through cuts or other skin damage or through mucous
membranes (such as the inside of the mouth and nose).
It is believed that the bacteria may be able to pass
through intact skin, but this is not known.
Once past the skin barrier, the bacteria enter the
blood stream and rapidly spread throughout the body.
The infection causes damage to the inner lining of
blood vessels. The liver, kidneys, heart, lungs, central
nervous system, and eyes may be affected.
There are two stages in the disease process. The first
stage is during the active Leptospira infection and is
called the bacteremic or septicemic phase. The bacteremic phase lasts from three to seven days and presents as
typical flu-like symptoms. During this phase, bacteria
can be found in the patient’s blood and cerebrospinal
fluid. The second stage, or immune phase, occurs either
immediately after the bacteremic stage or after a 1–3 day
symptom-free period. The immune phase can last up to
one month. During the immune phase, symptoms are
milder but meningitis (inflammation of spinal cord and
brain tissues) is common. Bacteria can be isolated only
from the urine during this second phase.

Causes and symptoms
Leptospirosis is caused by an infection with the
bacterium Leptospira interrogans. The bacteria are
spread through contact with urine from infected animals. Persons at an increased risk for leptospirosis
include farmers, miners, animal health care workers,
fish farmers and processors, sewage and canal workers,
cane harvesters, and soldiers. High-risk activities include
care of pets, hunting, trail biking, freshwater swimming,
rafting, canoeing, kayaking, and participating in sports
in muddy fields. One recent outbreak occurred in
Ireland following a canoe competition on a local river.
Symptoms of Leptospira infection occur within
7–12 days following exposure to the bacteria.
Because the symptoms can be nonspecific, most
people who have antibodies to Leptospira do not
remember having had an illness. Eighty-five to 90%
of the cases are not serious and clear up on their
own. Symptoms of the first stage of leptospirosis
last three to seven days and are: fever (100–105 8F
[37.8–40.6 8C]), severe headache, muscle pain, stomach
pain, chills, nausea, vomiting, back pain, joint pain,
neck stiffness, and extreme exhaustion. Cough and
body rash sometimes occur.
Following the first stage of disease, a brief symptomfree period occurs for most patients. The symptoms
GALE ENCYCLOPEDIA OF MEDICINE

Ten percent of the persons infected with
Leptospira develop a serious disease called Weil’s
syndrome. The symptoms of Weil’s syndrome are
more severe than those described above and there is
no distinction between the first and second stages of
disease. The hallmark of Weil’s syndrome is liver,
kidney, and blood vessel disease. The signs of severe
disease are apparent after 3–7 days of illness. In
addition to those listed above, symptoms of Weil’s
syndrome include jaundice (yellow skin and eyes),
decreased or no urine output, hypotension (low
blood pressure), rash, anemia (decreased number of
red blood cells), shock, and severe mental status
changes. Red spots on the skin, ‘‘blood shot’’ eyes,
and bloody sputum signal that blood vessel damage
and hemorrhage have occurred.

Treatment
Leptospirosis is treated with antibiotics, penicillin
(Bicillin, Wycillin), doxycycline (Monodox), ibramycin, or erythromycin (E-mycin, Ery-Tab). As of the
early 2000s, however, many doctors prefer to treat
patients with ceftriaxone, which is easier to use than
intravenous penicillin. Ciprofloxacin may be combined with other drugs in treating patients who
develop uveitis. It is generally agreed that antibiotic
treatment during the first few days of illness is helpful.
However, leptospirosis is often not diagnosed until
the later stages of illness. The benefit of antibiotic
treatment in the later stages of disease, however, is
controversial. A rare complication of antibiotic
therapy for leptospirosis is the occurrence of the
Jarisch-Herxheimer reaction, which is characterized
by fever, chills, headache, and muscle pain.
Patients with severe illness will require hospitalization for treatment and monitoring. Medication or other
treatment for pain, fever, vomiting, fluid loss, bleeding,
mental changes, and low blood pressure may be
provided. Patients with kidney failure will require
hemodialysis to remove waste products from the blood.

Diagnosis
Leptospirosis can be diagnosed and treated by
doctors who specialize in infectious diseases. During
the bacteremic phase of the disease, the symptoms
are relatively nonspecific. This often causes an initial
misdiagnosis because many diseases have similar
symptoms to leptospirosis. The later symptoms of
jaundice and kidney failure together with the
bacteremic phase symptoms suggest leptospirosis.
Blood samples will be tested to look for antibodies
to Leptospira interrogans. Blood samples taken
over a period of a few days would show an increase
in the number of antibodies. Isolating Leptospira
bacteria from blood, cerebrospinal fluid (performed
by spinal tap), and urine samples is diagnostic of
leptospirosis. It may take six weeks for Leptospira
to grow in laboratory media. Most insurance companies would cover the diagnosis and treatment of
this infection.
Several diagnostic tests for leptospirosis have
been devised in the early 2000s that are more accurate
as well as faster than standard culture. One test uses
flow cytometry light scatter analysis; this method can
evaluate a sample of infected serum in as little as 90
minutes. A second technique is an IgM-enzyme-linked
immunosorbent assay (ELISA), which detects the presence of IgM antibodies to L. interrogans in blood
serum samples.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The majority of patients infected with Leptospira
interrogans experience a complete recovery. Ten
percent of the patients will develop eye inflammation
(uveitis) up to one year after the illness. In the United
States, about one out of every 100 patients will die from
leptospirosis. Death is usually caused by kidney failure,
but has also been caused by myocarditis (inflammation
of heart tissue), septic shock (reduced blood flow to the
organs because of the bacterial infection), organ failure,
and/or poorly functioning lungs. Mortality is highest in
patients over 60 years of age.

Prevention
Persons who are at an extremely high risk (such
as soldiers who are training in wetlands) can be
pretreated with 200 mg of doxycycline once a week.
As of the early 2000s, there are no vaccines available
to prevent leptospirosis in humans, although such
vaccines have been formulated by veterinarians for
dogs, swine, and cattle.
There are many ways to decrease the chances of
being infected by Leptospira. These include:


Avoid swimming or wading in freshwater ponds and
slowly moving streams, especially those located near
farms.
2195

Leptospirosis

of the second stage vary in each patient. Most
patients have a low-grade fever, headache, vomiting,
and rash. Aseptic meningitis is common in the second
stage, symptoms of which include headache and
photosensitivity (sensitivity of the eye to light).
Leptospira can affect the eyes and make them cloudy
and yellow to orange colored. Vision may be blurred.

Lesch-Nyhan syndrome

KEY TERMS
Hemodialysis—The removal of waste products from
the blood stream in patients with kidney failure.
Blood is removed from a vein, passed through a
dialysis machine, and then put back into a vein.
Jarisch-Herxheimer reaction—A rare reaction to
the dead bacteria in the blood stream following
antibiotic treatment.
Meningitis—Inflammation of tissues in the brain and
spinal cord. Aseptic meningitis refers to meningitis
with no bacteria present in the cerebral spinal fluid.

Leptospirosis.’’ New Microbiologica 27 (April 2004):
149–154.
Yitzhaki, S., A. Barnea, A. Keysary, and E. Zahavy. ‘‘New
Approach for Serological Testing for Leptospirosis by
Using Detection of Leptospira Agglutination by Flow
Cytometry Light Scatter Analysis.’’ Journal of Clinical
Microbiology 42 (April 2004): 1680–1685.
ORGANIZATIONS

American Veterinary Medical Association (AVMA).
1931 North Meacham Road, Suite 100, Schaumburg,
IL 60173-4360. <http://www.avma.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Spirochete—Any of a family of spiral- or coil-shaped
bacteria known as Spirochetae. L. interrogans is a
spirochete, as well as the organisms that cause
syphilis and relapsing fever.

Belinda Rowland, PhD
Rebecca J. Frey, PhD

Zoonosis (plural, zoonoses)—Any disease of
animals that can be transmitted to humans.
Leptospirosis is an example of a zoonosis.

Lesch-Nyhan syndrome
Definition


Do not conduct canoe or kayak capsizing drills in
freshwater ponds. Use a swimming pool instead.



Boil or chemically treat pond or stream water before
drinking it or cooking with it.



Control rats and mice around the home.



Have pets and farm animals vaccinated against
Leptospira.



Wear protective clothing (gloves, boots, long pants,
and long-sleeved shirts) when working with wet soil
or plants.

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Infectious Diseases Caused by Spirochetes.’’ In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Boland, M., G. Sayers, T. Coleman, et al. ‘‘A Cluster of
Leptospirosis Cases in Canoeists following a
Competition on the River Liffey.’’ Epidemiology and
Infection 132 (April 2004): 195–200.
Faucher, J. F., B. Hoen, and J. M. Estavoyer. ‘‘The
Management of Leptospirosis.’’ Expert Opinion in
Pharmacotherapy 5 (April 2004): 819–827.
Vitale, G., C. La Russa, A. Galioto, et al. ‘‘Evaluation of an
IgM-ELISA Test for the Diagnosis of Human
2196

Lesch-Nyhan syndrome, which is also known as
HPRT deficiency or Kelley-Seegmiller syndrome, is a
rare genetic disorder that affects males. Males with
this syndrome develop physical handicaps, mental
retardation, and kidney problems. It is caused by a
total absence of a key enzyme that affects the level of
uric acid in the body. Self-injury or self-mutilation is a
distinctive feature of this genetic disease.

Description
Lesch-Nyhan syndrome was first described in
1964 by Drs. Michael Lesch and William Nyhan.
The enzyme deficiency that causes the disorder was
discovered in 1967 by a researcher named Seegmiller.
The syndrome is caused by a severe change (mutation) in a gene that encodes an enzyme known as
hypoxanthine-guanine phosphoribosyl transferase,
or HPRT. This gene was identified and sequenced
by Friedmann and colleagues in 1985. HPRT catalyzes a reaction that is necessary to prevent the
buildup of uric acid, a nitrogenous waste product
that is ordinarily excreted from the body through
the kidneys. A severe mutation in the HPRT gene
leads to an absence of HPRT enzyme activity
which, in turn, leads to markedly elevated uric acid
levels in the blood (hyperuricemia). This buildup of
uric acid is toxic to the body and is related to the
symptoms associated with the disease. Absence of
the HPRT enzyme activity is also thought to alter
GALE ENCYCLOPEDIA OF MEDICINE

Males with Lesch-Nyhan syndrome develop neurologic problems during infancy. Infants with LeschNyhan syndrome have weak muscle tone (hypotonia)
and are unable to develop normally. Affected males
develop uncontrollable writhing movements (athetosis) and muscle stiffness (spasticity) over time. Lack of
speech is also a common feature of Lesch-Nyhan syndrome. The most dramatic symptom of Lesch-Nyhan
syndrome, however, is the compulsive self-injury seen
in 85% of affected males. This self-injury involves the
biting of their own lips, tongue, and finger tips, as well
as head banging. This behavior leads to serious injury
and scarring.
Lesch-Nyhan syndrome affects approximately
one in 380,000 live births. It occurs evenly among
races. Almost always, only male children are affected,
although a few cases of the disorder in girls have been
reported. Women carriers usually do not have any
symptoms. Women carriers can occasionally develop
inflammation of the joints (gout) as they get older.

Causes and symptoms
Severe changes (mutations) in the HPRT gene
completely halt the activity of the enzyme HPRT.
There have been many different severe mutations identified in the HPRT gene. These mutations may be
different between families. The HPRT gene is located
on the X chromosome. Since the HPRT gene is located
on the X chromosome, Lesch-Nyhan syndrome is
considered X-liked. This means that it only affects
males.
A person’s sex is determined by their chromosomes. Males have one X chromosome and one
Y chromosome. Females, on the other hand, have two
X chromosomes. Males who possess a severe mutation
in their HPRT gene will develop Lesch-Nyhan syndrome. Females who possess a severe mutation in their
HPRT gene will not. They are considered to be carriers. This is because females have another X chromosome without the mutation that prevents them from
getting this disease. If a woman is a carrier, she has a
50% risk with any pregnancy to pass on her X chromosome with the mutation. Therefore, with every
male pregnancy she has a 50% risk to have an affected
son, and with every female pregnancy she has a 50%
risk to have a daughter who is a carrier.
GALE ENCYCLOPEDIA OF MEDICINE

At birth, males with Lesch-Nyhan syndrome
appear completely normal. Development is usually
normal for the first few months. Symptoms develop
between three to six months of age. Sand-like crystals
of uric acid in the diapers may be one of the first
symptoms of the disease. The baby may be unusually
irritable. Typically, the first sign of nervous system
impairment is the inability to lift their head or sit up
at an appropriate age. Many patients with LeschNyhan will never learn to walk. By the end of the
first year, writhing motions (athetosis), and spasmodic
movements of the limbs and facial muscles (chorea)
are clear evidence of defective motor development.
The compulsive self-injury associated with LeschNyhan syndrome begins, on average, at three years. The
self-injury begins with biting of the lips and tongue. As
the disease progresses, affected individuals frequently
develop finger biting and head banging. The self-injury
can increase during times of stress.
Males with Lesch-Nyhan disease may also
develop kidney damage due to kidney stones. Swollen
and tender joints (gout) is another common problem.

Diagnosis
The diagnosis of Lesch-Nyhan syndrome is based
initially on the distinctive pattern of the child’s symptoms, most commonly involuntary muscle movements
or failure to crawl and walk at the usual ages. In some
cases the first symptom is related to overproduction of
uric acid; the parents notice ‘‘orange sand’’ in the
child’s diapers. The ‘‘sand’’ is actually crystals of uric
acid tinged with blood.
Measuring the amount of uric acid in a person’s
blood or urine can not definitively diagnose LeschNyhan syndrome. It is diagnosed by measuring the
activity of the HPRT enzyme through a blood test.
When the activity of the enzyme is very low it is diagnostic of Lesch-Nyhan syndrome. It can also be diagnosed by DNA testing. This is also a blood test. DNA
testing checks for changes (mutations) in the HPRT
gene. Results from DNA testing are helpful in confirming the diagnosis and also when the child’s family is
interested in prenatal testing for future pregnancies.
Prenatal diagnosis is possible by DNA testing of
fetal tissue drawn by amniocentesis or chorionic villus
sampling (CVS). Fetuses should be tested if the mother
is a carrier of a change (mutation) in her HPRT gene.
A woman is at risk of being a carrier if she has a son with
Lesch-Nyhan syndrome or someone in her family has
Lesch-Nyhan syndrome. Any woman at risk of being a
carrier should have DNA testing through a blood test.
2197

Lesch-Nyhan syndrome

the chemistry of certain parts of the brain, such as the
basal ganglia, affecting neurotransmitters (chemicals
used for communication between nerve cells), acids,
and other chemicals. This change in the nervous system is also related to the symptoms associated with
Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome

KEY TERMS
Amniocentesis—A procedure performed at 16-18
weeks of pregnancy in which a needle is inserted
through a woman’s abdomen into her uterus to
draw out a small sample of the amniotic fluid
from around the baby. Either the fluid itself or
cells from the fluid can be used for a variety of
tests to obtain information about genetic disorders
and other medical conditions in the fetus.
Athetosis—A condition marked by slow, writhing,
involuntary muscle movements.
Basal ganglia—A section of the brain responsible
for smooth muscular movement.
Chorea—Involuntary, rapid, jerky movements.
Chorionic villus sampling (CVS)—A procedure
used for prenatal diagnosis at 10-12 weeks gestation.
Under ultrasound guidance a needle is inserted
either through the mother’s vagina or abdominal
wall and a sample of cells is collected from around
the early embryo. These cells are then tested for
chromosome abnormalities or other genetic diseases.
Enzyme—A protein that catalyzes a biochemical
reaction or change without changing its own structure or function.
Mutation—A permanent change in the genetic
material that may alter a trait or characteristic of
an individual, or manifest as disease, and can be
transmitted to offspring.
Neurotransmitter—Chemical in the brain that
transmits information from one nerve cell to another.
Palsy—Uncontrolable tremors.
Spasticity—Increased mucle tone, or stiffness,
which leads to uncontrolled, awkward movements.

Treatment
There are no known treatments for the neurological defects of Lesch-Nyhan. Allopurinol (Aloprim,
Zyloprim), a drug usually prescribed to lower the
risk of gout attacks, can lower blood uric acid levels.
This medication is a preventive; it does not correct
many of the symptoms of Lesch-Nyhan. Other drugs
that are given to manage spasticity include baclofen
(Lioresal), which is a muscle relaxant, and benzodiazepine tranquilizers.
Some patients with Lesch-Nyhan syndrome have
their teeth removed to prevent self-injury. Restraints
may be recommended to reduce self-destructive behaviors, although some patients can be managed with a
2198

combination of behavioral modification therapy and
medications.

Prognosis
With strong supportive care, infants born with
Lesch-Nyhan can live into adulthood with symptoms
continuing throughout life. Few live beyond 40, however, with death usually resulting either from kidney
failure or from aspiration pneumonia. Sudden unexpected death from respiratory failure is common in
these patients.
At present, there are no preventive measures for
Lesch-Nyhan syndrome. However, recent studies have
indicated that this genetic disorder may be a good
candidate for treatment with gene replacement therapy. Unfortunately, the technology necessary to
implement this therapy has not yet been perfected.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Cerebral Palsy Syndromes.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Jinnah, H. A., and Theodore Friedmann. ‘‘Lesch-Nyhan
Disease and Its Variants.’’ The Metabolic and Molecular
Bases of Inherited Disease. New York: McGraw-Hill,
2001.
PERIODICALS

Jinnah, Hyder, MD, PhD. ‘‘Lesch-Nyhan Syndrome.’’
eMedicine January 25, 2002. <http://
www.emedicine.com/neuro/topic630.htm>.
Mak, B. S., et al. ‘‘New Mutations of the HPRT Gene in
Lesch-Nyhan Syndrome.’’ Pediatric Neurology October
2000: 332–335.
Visser, J.E., et al. ‘‘Lesch-Nyhan Disease and the Basal
Ganglia.’’ Brain Research Reviews November 1999:
450–469.
Willers, I. ‘‘Germline Mosaicism Complicates Molecular
Diagnosis of Lesch-Nyhan Syndrome.’’ Prenatal
Diagnosis 24 (September 2004): 737–740.
ORGANIZATIONS

Alliance of Genetic Support Groups. 4301 Connecticut Ave.
NW, Suite 404, Washington, DC 20008. (202) 966-5557.
Fax: (202) 966-8553. <http://
www.geneticalliance.org>.
International Lesch-Nyhan Disease Association. 114
Winchester Way, Shamong, NJ 08088-9398. (215)
677-4206.
Lesch-Nyhan Syndrome Registry. New York University
School of Medicine, Department of Psychiatry, 550
First Ave., New York, NY 10012. (212) 263-6458.
National Organization for Rare Disorders (NORD).
55 Kenosia Avenue, P. O. Box 1968, Danbury,
GALE ENCYCLOPEDIA OF MEDICINE

Leukemia stains

CT 06813-1968. (203) 744-0100. Fax: (203) 798-2291.
<http://www.rarediseases.org>.
OTHER

GeneClinics. <http://www.geneclinics.org/profiles/lns/
details.html>.
Pediatric Database(PEDBASE). <http://www.icondata.
com/health/pedbase/files/LESCH-NY.HTM>.

Holly Ann Ishmael, M.S.
Rebecca J. Frey, PhD

Leukemia stains
Definition
Leukemia stains are laboratory tests done on bone
marrow or blood samples to help diagnose specific
types of leukemia.

Purpose
Leukemia stains are done to diagnose and classify
leukemia. Blood contains red cells, several varieties of
white cells, and platelets. Cancerous overproduction
of any one type of cell produces one of many types of
leukemia. A patient’s specific type of leukemia must be
classified in order to provide the best treatment and
most accurate prognosis.
The type and maturity of the cells involved are
identified by analyzing blood and bone marrow under
a microscope. Often, however, the abnormality or
immaturity of the cells make it difficult to identify
the cell types with certainty. Special leukemia stains
help to distinguish one cell type from another.

Description
Special stains are added to bone marrow or blood
that has been smeared on a microscope slide. Cell
types react differently to the chemicals in the stains.
If the patient has few white cells, a buffy coat
smear is made. A tube of blood is spun in a centrifuge.
Red cells fall, plasma rises, and white cells settle in a
thin middle layer called the buffy coat. The smear is
made from this layer.

A magnified stain of chronic lymphocytic leukemia cells.
(Custom Medical Stock Photo. Reproduced by permission.)

Periodic acid-Schiff stain (PAS)
The PAS stain is primarily used to identify erythroleukemia, a leukemia of immature red blood cells.
These cells stain a bright fuchsia.
Terminal deoxynucleotidyl transferase stain (TdT)
The TdT stain differentiates between acute lymphoblastic leukemia (cells stain positive) and acute
myelogenous leukemia (cells stain negative).
Leukocyte alkaline phosphatase (LAP)
The LAP stain is used to determine if an increase
of cells is due to chronic myelogenous leukemia or a
noncancerous reaction to an infection or similar conditions. Cells from a noncancerous reaction stain positive with many intense blue granules; cells from
chronic myelogenous leukemia have few blue
granules.
Tartrate-resistant acid phosphatase stain (TRAP)
The TRAP stain is primarily used to identify hairy
cell leukemia cells. These cells stain with purple to dark
red granules.
Myeloperoxidase stain
The myeloperoxidase stain distinguishes between
the immature cells in acute myeloblastic leukemia
(cells stain positive) and those in acute lymphoblastic
leukemia (cells stain negative).

Sudan black B stain
This stain distinguishes between acute lymphoblastic leukemia (cells stain positive) and acute myeloblastic leukemia (cells stain negative).
GALE ENCYCLOPEDIA OF MEDICINE

Leukocyte specific esterase
This stain identifies granulocytes, which show red
granules.
2199

Leukemias, acute

Abnormal results

KEY TERMS
Bone marrow—The spongy tissue inside large
bones where blood cells are formed.
Buffy coat—The thin layer of concentrated white
blood cells that forms when a tube of blood is spun
in a centrifuge.
Leukemia—Any of several cancers of the bone
marrow characterized by the abnormal increase
of a type of blood cell.

Leukemia stain results that help diagnosis and
classify leukemia are supported by the results of
other laboratory tests and the person’s clinical
condition.
Resources
BOOKS

Fischbach, Francis. Manual of Laboratory and Diagnostic
Tests. Philadelphia: Lippincott, 1996.

Nancy J. Nordenson

Leukemia stains—Special stains added to smears of
blood or bone marrow, performed to diagnose and
classify leukemia.

Leukocyte nonspecific esterase
Nonspecific esterase stain identifies monocytes
and immature platelets (megakaryocytes), which
show positive black granules.

Preparation
Leukemia stains are done on smears of blood or
bone marrow. To collect blood, a healthcare worker
draws blood from a vein in the inner elbow region.
Collection of the sample takes only a few minutes.
When bone marrow is needed, the person is given
local anesthesia. Then the physician inserts a needle
through the skin and into the bone–usually the breast
bone or hip bone–and 0.5-2 mL of bone marrow is
withdrawn. This procedure takes approximately 30
minutes.

Aftercare
Patients sometimes feel discomfort or bruising at
the puncture site after blood collection. They may also
become dizzy or faint. Pressure to the puncture site
until the bleeding stops reduces bruising. Warm packs
to the puncture site relieve discomfort.
Collection of bone marrow is done under a physician’s supervision. The patient is asked to rest after the
procedure and is watched for weakness and signs of
bleeding.

Normal results
A normal blood or bone marrow smear shows no
evidence of leukemic cells. The expected reaction of
cells varies with the type of stain.
2200

Leukemias, acute
Definition
Leukemia is a cancer that starts in the organs that
make blood, namely the bone marrow and the lymph
system. Depending on their characteristics, leukemias
can be divided into two broad types. Acute leukemias
are the rapidly progressing leukemias, while the
chronic leukemias progress more slowly. The vast
majority of the childhood leukemias are of the acute
form.

Description
The cells that make up blood are produced in the
bone marrow and the lymph system. The bone marrow is the spongy tissue found in the large bones of the
body. The lymph system includes the spleen (an organ
in the upper abdomen), the thymus (a small organ
beneath the breastbone), and the tonsils (an organ in
the throat). In addition, the lymph vessels (tiny tubes
that branch like blood vessels into all parts of the
body) and lymph nodes (pea-shaped organs that are
found along the network of lymph vessels) are also
part of the lymph system. The lymph is a milky fluid
that contains cells. Clusters of lymph nodes are found
in the neck, underarm, pelvis, abdomen, and chest.
The cells found in the blood are the red blood cells
(RBCs), which carry oxygen and other materials to all
tissues of the body; white blood cells (WBCs) that fight
infection; and the platelets, which play a part in the
clotting of the blood. The white blood cells can be
further subdivided into three main types: granulocytes, monocytes, and lymphocytes.
The granulocytes, as their name suggests, have
particles (granules) inside them. These granules
GALE ENCYCLOPEDIA OF MEDICINE

heart condition. Friend’s decision to pursue a career in
medicine may well have been influenced by her father’s
death and by her mother’s occupation as a pharmacist. As a
child, Friend read books about bacteriologists and, by age
ten, she knew that she wanted to study bacteriology. She
attended Hunter College, enlisting in the U.S. Navy after
her graduation in 1944.

(Library of Congress.)

Charlotte Friend was born to Russian immigrants,
Morris Friend and Cecilia (Wolpin), on March 11, 1921,
in New York City. At three years of age, her father died of a

contain special proteins (enzymes) and several other
substances that can break down chemicals and destroy
microorganisms, such as bacteria. Monocytes are the
second type of white blood cell. They are also important in defending the body against pathogens.
The lymphocytes form the third type of white
blood cell. There are two main types of lymphocytes:
T lymphocytes and B lymphocytes. They have different functions within the immune system. The B cells
protect the body by making ‘‘antibodies.’’ Antibodies
are proteins that can attach to the surfaces of bacteria
and viruses. This ‘‘attachment’’ sends signals to many
other cell types to come and destroy the antibodycoated organism. The T cells protect the body against
viruses. When a virus enters a cell, it produces certain
proteins that are projected onto the surface of the
infected cell. The T cells recognize these proteins and
make certain chemicals that are capable of destroying
the virus-infected cells. In addition, the T cells can
destroy some types of cancer cells.
The bone marrow makes stem cells, which are the
precursors of the different blood cells. These stem cells
mature through stages into either RBCs, WBCs, or
GALE ENCYCLOPEDIA OF MEDICINE

Friend attended Yale University, earning her Ph.D. in
bacteriology in 1950. After working for the Memorial
Sloan-Kettering Institute for Cancer Research, she became
an associate professor at Cornell University in 1952. Friend
began researching cancer and became particularly interested in leukemia and its cause. She believed that a virus
caused the disease and confirmed this theory by using an
electron microscope to photograph the virus in mice. Her
findings were initially met with much skepticism but she
was able to develop a vaccine that was used successfully
with mice, which added credibility to her theory. Her
breakthroughs have led medical researchers to new methods of treating cancer and to a greater understanding of the
disease.
Friend was a prolific writer who published 113 original papers, 49 abstracts, book chapters, and reviews, many
of which she completed individually. She was diagnosed
with lymphoma and died on January 13, 1987.

platelets. In acute leukemias, the maturation process
of the white blood cells is interrupted. The immature
cells (or ‘‘blasts’’) proliferate rapidly and begin to
accumulate in various organs and tissues, thereby
affecting their normal function. This uncontrolled
proliferation of the immature cells in the bone marrow
affects the production of the normal red blood cells
and platelets as well.
Acute leukemias are of two types: acute lymphocytic leukemia and acute myelogenous leukemia.
Different types of white blood cells are involved in the
two leukemias. In acute lymphocytic leukemia (ALL), it
is the T or the B lymphocytes that become cancerous.
The B cell leukemias are more common than T cell
leukemias. Acute myelogenous leukemia, also known
as acute nonlymphocytic leukemia (ANLL), is a cancer
of the monocytes and/or granulocytes.
Leukemias account for 2% of all cancers. Because
leukemia is the most common form of childhood cancer,
it is often regarded as a disease of childhood. However,
leukemias affect nine times as many adults as children.
Half of the cases occur in people who are 60 years of age
or older. The incidence of acute and chronic leukemias is
2201

Leukemias, acute

C H A R L O T T E F R I E N D (1921–1987)

Leukemias, acute

about the same. According to the estimates of the
American Cancer Society (ACS), approximately
29,000 new cases of leukemia were diagnosed in 1998.

Causes and symptoms
Leukemia strikes both sexes and all ages. The
human T-cell leukemia virus (HTLV-I) is believed to
be the causative agent for some kinds of leukemias.
However, the cause of most leukemias is not known.
Acute lymphoid leukemia (ALL) is more common
among Caucasians than among African-Americans,
while acute myeloid leukemia (AML) affects both
races equally. The incidence of acute leukemia is
slightly higher among men than women. People with
Jewish ancestry have a higher likelihood of getting
leukemia. A higher incidence of leukemia has also
been observed among persons with Down syndrome
and some other genetic abnormalities.
Exposure to ionizing radiation and to certain
organic chemicals, such as benzene, is believed to
increase the risk of getting leukemia. Having a history
of diseases that damage the bone marrow, such as
aplastic anemia, or a history of cancers of the lymphatic system puts people at a high risk for developing
acute leukemias. Similarly, the use of anticancer medications, immunosuppressants, and the antibiotic
chloramphenicol are also considered risk factors for
developing acute leukemias.
The symptoms of leukemia are generally vague
and non-specific. A patient may experience all or
some of the following symptoms:


weakness or chronic fatigue



fever of unknown origin



weight loss that is not due to dieting or exercise



frequent bacterial or viral infections



headaches



skin rash



non-specific bone pain



easy bruising



bleeding from gums or nose



blood in urine or stools



enlarged lymph nodes and/or spleen



abdominal fullness

Diagnosis
Like all cancers, acute leukemias are best treated
when found early. There are no screening tests
available.
2202

An enhanced transmission electron microscopy (TEM) image
of acute myelogenous leukemia cells. (Photograph by Robert
Becker, Ph.D., Custom Medical Stock Photo. Reproduced by
permission.)

If the doctor has reason to suspect leukemia, he
or she will conduct a very thorough physical examination to look for enlarged lymph nodes in the
neck, underarm, and pelvic region. Swollen gums,
enlarged liver or spleen, bruises, or pinpoint red
rashes all over the body are some of the signs of
leukemia. Urine and blood tests may be ordered to
check for microscopic amounts of blood in the
urine and to obtain a complete differential blood
count. This count will give the numbers and percentages of the different cells found in the blood. An
abnormal blood test might suggest leukemia; however, the diagnosis has to be confirmed by more
specific tests.
The doctor may perform a bone marrow biopsy to
confirm the diagnosis of leukemia. During the biopsy,
a cylindrical piece of bone and marrow is removed.
The tissue is generally taken out of the hipbone. These
samples are sent to the laboratory for examination. In
addition to diagnosis, the biopsy is also repeated during the treatment phase of the disease to see if the
leukemia is responding to therapy.
A spinal tap (lumbar puncture) is another procedure that the doctor may order to diagnose leukemia.
In this procedure, a small needle is inserted into the
spinal cavity in the lower back to withdraw some
cerebrospinal fluid and to look for leukemic cells.
GALE ENCYCLOPEDIA OF MEDICINE

Because leukemia cells can spread to all the organs
via the blood stream and the lymph vessels, surgery is
not considered an option for treating leukemias.

An enhanced scanning electron microscopy (SEM) image of
acute myelogenous leukemia cells. (Photograph by Robert
Becker, Ph.D., Custom Medical Stock Photo. Reproduced by
permission.)

Standard imaging tests, such as x rays, computed
tomography scans (CT scans), and magnetic resonance
imaging (MRI) may be used to check whether the
leukemic cells have invaded other areas of the body,
such as the bones, chest, kidneys, abdomen, or brain.
A gallium scan or bone scan is a test in which a radioactive chemical is injected into the body. This chemical
accumulates in the areas of cancer or infection, allowing them to be viewed with a special camera.

Treatment
There are two phases of treatment for leukemia.
The first phase is called ‘‘induction therapy.’’ As the
name suggests, during this phase, the main aim of the
treatment is to reduce the number of leukemic cells as
far as possible and induce a remission in the patient.
Once the patient shows no obvious signs of leukemia
(no leukemic cells are detected in blood tests and
bone marrow biopsies), the patient is said to be in
remission. The second phase of treatment is then
initiated. This is called continuation or maintenance
therapy, and the aim in this case is to kill any remaining cells and to maintain the remission for as long as
possible.
Chemotherapy is the use of drugs to kill cancer
cells. It is usually the treatment of choice and is used
to relieve symptoms and achieve long-term remission
GALE ENCYCLOPEDIA OF MEDICINE

Radiation therapy, which involves the use of x rays
or other high-energy rays to kill cancer cells and shrink
tumors, may be used in some cases. For acute leukemias, the source of radiation is usually outside the
body (external radiation therapy). If the leukemic
cells have spread to the brain, radiation therapy can
be given to the brain.
Bone marrow transplantation is a process in which
the patient’s diseased bone marrow is replaced with
healthy marrow. There are two ways of doing a bone
marrow transplant. In an allogeneic bone marrow
transplant, healthy marrow is taken from a donor
whose tissue is either the same as or very closely
resembles the patient’s tissues. The donor may be a
twin, a brother or sister (sibling), or a person who is
not related at all. First, the patient’s bone marrow is
destroyed with very high doses of chemotherapy and
radiation therapy. Healthy marrow from the donor is
then given to the patient through a needle in a vein to
replace the destroyed marrow.
In the second type of bone marrow transplant,
called an autologous bone marrow transplant, some
of the patient’s own marrow is taken out and treated
with a combination of anticancer drugs to kill all the
abnormal cells. This marrow is then frozen to save it.
The marrow remaining in the patient’s body is
destroyed with high-dose chemotherapy and radiation
therapy. The marrow that was frozen is then thawed
and given back to the patient through a needle in a
vein. This mode of bone marrow transplant is currently being investigated in clinical trials.
Biological therapy or immunotherapy is a mode
of treatment in which the body’s own immune system
is harnessed to fight the cancer. Substances that are
routinely made by the immune system (such as growth
factors, hormones, and disease-fighting proteins) are
either synthetically made in a laboratory or their effectiveness is boosted and they are then put back into the
patient’s body. This treatment mode is also being
2203

Leukemias, acute

of the disease. Generally, combination chemotherapy, in which multiple drugs are used, is more efficient than using a single drug for the treatment. Some
drugs may be administered intravenously through a
vein in the arm; others may be given by mouth in the
form of pills. If the cancer cells have invaded the
brain, then chemotherapeutic drugs may be put into
the fluid that surrounds the brain through a needle in
the brain or back. This is known as intrathecal
chemotherapy.

Leukemias, chronic

KEY TERMS
Antibodies—Proteins made by the B lymphocytes
in response to the presence of infectious agents,
such as bacteria or viruses, in the body.
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic purposes.
Chemotherapy—Treatment with drugs that act
against cancer.
Computerized tomography (CT) scan—A series of
x rays put together by a computer in order to form
detailed pictures of areas inside the body.
Cytokines—Chemicals made by the cells that act
on other cells to stimulate or inhibit their function.
Cytokines that stimulate growth are called ‘‘growth
factors.’’
Immunotherapy—Treatment of cancer by stimulating the body’s immune defense system.
Lumbar puncture—A procedure in which the doctor inserts a small needle into the spinal cavity in
the lower back to withdraw some spinal fluid for
testing. Also known as a ‘‘spinal tap.’’
Magnetic resonance imaging (MRI)—A medical
procedure using a magnet linked to a computer to
picture areas inside the body.
Maturation—The process by which stem cells
transform from immature cells without a specific
function into a particular type of blood cell with
defined functions.
Radiation therapy—Treatment using high-energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Remission—A disappearance of a disease as a result
of treatment. Complete remission means that all
disease is gone. Partial remission means that the
disease is significantly improved by treatment, but
residual traces of the disease are still present.

(ALL) and the chronic leukemias. In the last 15 to 20
years, the five-year survival rate for patients with ALL
has increased from 38% to 57%.
Interestingly enough, since most childhood leukemias are of the ALL type, chemotherapy has been
highly successful in their treatment. This is because
chemotherapeutic drugs are most effective against
actively growing cells. Due to the new combinations
of anticancer drugs being used, the survival rates
among children with ALL have improved dramatically. Eighty percent of the children diagnosed with
ALL now survive for five years or more, as compared
to 50% in the late 1970s.

Prevention
Most cancers can be prevented by changes in lifestyle or diet, which will reduce the risk factors.
However, in leukemias, there are no such known risk
factors. Therefore, at the present time, no way is known
to prevent leukemias from developing. People who are
at an increased risk for developing leukemia because of
proven exposure to ionizing radiation or exposure to
the toxic liquid benzene, and people with Down syndrome, should undergo periodic medical checkups.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
Cancer Research Institute. 681 Fifth Ave., New York, N.Y.
10022. (800) 992-2623. <http://
www.cancerresearch.org>.
Leukemia Society of America, Inc. 600 Third Ave., New
York, NY 10016. (800) 955-4572. <http://
www.leukemia.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
Oncolink. University of Pennsylvania Cancer Center.
<http://cancer.med.upenn.edu>.

Lata Cherath, PhD

investigated in clinical trials all over the country at
major cancer centers.

Prognosis
Like all cancers, the prognosis for leukemia
depends on the patient’s age and general health.
According to statistics, more than 60% of the patients
with leukemia survive for at least a year after diagnosis. Acute myelocytic leukemia (AML) has a poorer
prognosis rate than acute lymphocytic leukemias
2204

Leukemias, chronic
Definition
Chronic leukemia is a disease in which too many
white blood cells are made in the bone marrow.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Chronic leukemia is a cancer that starts in the
blood cells made in the bone marrow. The bone marrow is the spongy tissue found in the large bones of the
body. The bone marrow makes precursor cells called
‘‘blasts’’ or ‘‘stem cells’’ that mature into different
types of blood cells. Unlike acute leukemias, in which
the process of maturation of the blast cells is interrupted, in chronic leukemias, the cells do mature and
only a few remain as immature cells. However, even
though the cells appear normal, they do not function
as normal cells.
The different types of cells that are produced in
the bone marrow are red blood cells (RBCs), which
carry oxygen and other materials to all tissues of the
body; white blood cells (WBCs), which fight infection;
and platelets, which play a part in the clotting of the
blood. The white blood cells can be further subdivided
into three main types: the granulocytes, monocytes,
and the lymphocytes.
The granulocytes, as their name suggests, have
granules (particles) inside them. These granules contain special proteins (enzymes) and several other substances that can break down chemicals and destroy
microorganisms such as bacteria.
Monocytes are the second type of white blood cell.
They are also important in defending the body against
pathogens.
The lymphocytes form the third type of white
blood cell. There are two main types of lymphocytes:
T lymphocytes and B lymphocytes. They have different functions within the immune system. The B cells
protect the body by making ‘‘antibodies.’’ Antibodies
are proteins that can attach to the surfaces of bacteria
and viruses. This attachment sends signals to many
other cell types to come and destroy the antibodycoated organism. The T cell protects the body against
viruses. When a virus enters a cell, it produces certain
proteins that are projected onto the surface of the
infected cell. The T cells can recognize these proteins
and produce certain chemicals (cytokines) that are
capable of destroying the virus-infected cells. In addition, the T cells can destroy some types of cancer cells.
Chronic leukemias develop very gradually. The
abnormal lymphocytes multiply slowly, but in a
poorly regulated manner. They live much longer and
thus their numbers build up in the body. The two types
GALE ENCYCLOPEDIA OF MEDICINE

of chronic leukemias can be easily distinguished under
the microscope. Chronic lymphocytic leukemia (CLL)
involves the T or B lymphocytes. B cell abnormalities
are more common than T cell abnormalities. T cells
are affected in only 5% of the patients. The T and B
lymphocytes can be differentiated from the other types
of white blood cells based on their size and by the
absence of granules inside them. In chronic myelogenous leukemia (CML), the cells that are affected are the
granulocytes.
Chronic lymphocytic leukemia (CLL) often has
no symptoms at first and may remain undetected for
a long time. Chronic myelogenous leukemia (CML),
on the other hand, may progress to a more acute form.
Chronic leukemias account for 1.2% of all cancers. Because leukemia is the most common form of
childhood cancer, it is often regarded as a disease of
childhood. However, leukemias affect nine times as
many adults as children. In chronic lymphoid leukemia, 90% of the cases are seen in people who are
50 years or older, with the average age at diagnosis
being 65. The incidence of the disease increases with
age. It is almost never seen in children. Chronic myeloid
leukemias are generally seen in people in their mid-40s.
It accounts for about 4% of childhood leukemia
cases. According to the estimates of the American
Cancer Society (ACS), approximately 29,000 new
cases of leukemia will be diagnosed in 1998.

Causes and symptoms
Leukemia strikes both sexes and all ages.
Although the cause is unknown, chronic leukemia is
linked to genetic abnormalities and environmental
factors. For example, exposure to ionizing radiation
and to certain organic chemicals, such as benzene, is
believed to increase the risks for getting leukemia.
Chronic leukemia occurs in some people who are
infected with two human retroviruses (HTLV-I and
HTLV-II). An abnormal chromosome known as the
Philadelphia chromosome is seen in 90% of those with
CML. The incidence of chronic leukemia is slightly
higher among men than women.
The symptoms of chronic leukemia are generally
vague and non-specific. In chronic lymphoid leukemia
(CLL), a patient may experience all or some of the
following symptoms:


swollen lymph nodes



an enlarged spleen, which could make the patient
complain of abdominal fullness



chronic fatigue
2205

Leukemias, chronic

Depending on the type of white blood cell that is
involved, chronic leukemia can be classified as chronic
lymphocytic leukemia or chronic myeloid leukemia.

Leukemias, chronic



a general feeling of ill-health



fever of unknown origin



night sweats



weight loss that is not due to dieting or exercise



frequent bacterial or viral infections

In the early stages of chronic myeloid leukemia
(CML), the symptoms are more or less similar to CLL.
In the later stages of the disease, the patient may
experience these symptoms:


non-specific bone pain



bleeding problems



mucus membrane irritation



frequent infections



a pale color due to a low red blood cell count
(anemia)



swollen lymph glands



fever



night sweats

Diagnosis
There are no screening tests available for chronic
leukemias. The detection of these diseases may occur
by chance during a routine physical examination.
If the doctor has reason to suspect leukemia, he or
she will conduct a very thorough physical examination
to look for enlarged lymph nodes in the neck, underarm, and pelvic region. Swollen gums, an enlarged
liver or spleen, bruises, or pinpoint red rashes all over
the body are some of the signs of leukemia. Urine and
blood tests may be ordered to check for microscopic
amounts of blood in the urine and to obtain a complete differential blood count. This count will give the
numbers and percentages of the different cells found in
the blood. An abnormal blood test might suggest leukemia; however, the diagnosis has to be confirmed by
more specific tests.
The doctor may perform a bone marrow biopsy to
confirm the diagnosis of leukemia. During the bone
marrow biopsy, a cylindrical piece of bone and marrow is removed. The tissue is generally taken out of the
hipbone. These samples are sent to the laboratory for
examination. In addition to diagnosis, bone marrow
biopsy is also done during the treatment phase of the
disease to see if the leukemia is responding to therapy.
Standard imaging tests such as x rays, computed
tomography scans (CT scans), and magnetic resonance
imaging (MRI) may be used to check whether the
2206

leukemic cells have invaded other organs of the body,
such as the bones, chest, kidneys, abdomen, or brain.

Treatment
The treatment depends on the specific type of
chronic leukemia and its stage. In general, chemotherapy is the standard approach to both CLL and CML.
Radiation therapy is occasionally used. Because leukemia cells can spread to all the organs via the blood
stream and the lymph vessels, surgery is not considered an option for treating leukemias.
Bone marrow transplantation (BMT) is becoming
the treatment of choice for CML because it has the
possibility of curing the illness. BMT is generally not
considered an option in treating CLL because CLL
primarily affects older people, who are not considered
to be good candidates for the procedure.
In BMT, the patient’s diseased bone marrow is
replaced with healthy marrow. There are two ways of
doing a bone marrow transplant. In an allogeneic
bone marrow transplant, healthy marrow is taken
from another person (donor) whose tissue is either
the same or very closely resembles the patient’s tissues.
The donor may be a twin, a sibling, or a person who is
not related at all. First, the patient’s bone marrow is
destroyed with very high doses of chemotherapy and
radiation therapy. To replace the destroyed marrow,
healthy marrow from the donor is given to the patient
through a needle in the vein.
In the second type of bone marrow transplant,
called an autologous bone marrow transplant, some
of the patient’s own marrow is taken out and treated
with a combination of anticancer drugs to kill all the
abnormal cells. This marrow is then frozen to save it.
The marrow remaining in the patient’s body is then
destroyed with high dose chemotherapy and radiation
therapy. Following that, the patient’s own marrow
that was frozen is thawed and given back to the patient
through a needle in the vein. This mode of bone marrow transplant is currently being investigated in clinical trials.
In chronic lymphoid leukemia (CLL), chemotherapy is generally the treatment of choice. Depending on
the stage of the disease, single or multiple drugs may
be given. Drugs commonly prescribed include steroids, chlorambucil, fludarabine, and cladribine. Low
dose radiation therapy may be given to the whole
body, or it may be used to alleviate the symptoms
and discomfort due to an enlarged spleen and lymph
nodes. The spleen may be removed in a procedure
called a splenectomy.
GALE ENCYCLOPEDIA OF MEDICINE

Antibodies—Proteins made by the B lymphocytes
in response to the presence of infectious agents,
such as bacteria or viruses, in the body.
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Chemotherapy—Treatment with drugs that act
against cancer.
Computerized tomography (CT) scan—A series of
x rays put together by a computer in order to form
detailed pictures of areas inside the body.
Cytokines—Chemicals made by the cells that act
on other cells to stimulate or inhibit their function.
Cytokines that stimulate growth are called ‘‘growth
factors.’’
Immunotherapy—Treatment of cancer by stimulating the body’s immune defense system.
Lumbar puncture—A procedure in which the doctor inserts a small needle into the spinal cavity in
the lower back to withdraw some spinal fluid for
testing. Also known as a ‘‘spinal tap.’’
Magnetic resonance imaging (MRI)—A medical
procedure using a magnet linked to a computer to
picture areas inside the body.
Maturation—The process by which stem cells
transform from immature cells without a specific
function into a particular type of blood cell with
defined functions.
Radiation therapy—Treatment using high-energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Remission—A disappearance of a disease as a
result of treatment. Complete remission means that
all disease is gone. Partial remission means that
the disease is significantly improved by treatment, but residual traces of the disease are still
present.

spleen. For chronic leukemias, the source of radiation
is usually outside the body (external radiation therapy). If the leukemic cells have spread to the brain,
radiation therapy can be directed at the brain. As the
disease progresses, the spleen may be removed in an
attempt to try to control the pain and to improve the
blood counts.
In the acute phase of CML, aggressive chemotherapy is given. Combination chemotherapy, in which
multiple drugs are used, is more efficient than using a
single drug for the treatment. The drugs may either be
administered intravenously through a vein in the arm
or by mouth in the form of pills. If the cancer cells have
invaded the central nervous system (CNS), chemotherapeutic drugs may be put into the fluid that
surrounds the brain through a needle in the brain or
back. This is known as intrathecal chemotherapy.
Biological therapy or immunotherapy is a mode
of treatment in which the body’s own immune system
is harnessed to fight the cancer. Substances that are
routinely made by the immune system (such as growth
factors, hormones, and disease-fighting proteins) are
either synthetically made in a laboratory, or their
effectiveness is boosted and they are then put back
into the patient’s body. This treatment mode is also
being investigated in clinical trials all over the country
at major cancer centers.

Prognosis
The prognosis for leukemia depends on the
patient’s age and general health. According to statistics, in chronic lymphoid leukemia, the overall survival for all stages of the disease is nine years. Most of
the deaths in people with CLL are due to infections or
other illnesses that occur as a result of the leukemia.
In CML, if bone marrow transplantation is performed within one to three years of diagnosis, 50-60%
of the patients survive three years or more. If the
disease progresses to the acute phase, the prognosis is
poor. Less than 20% of these patients go into
remission.

Prevention
In chronic myeloid leukemia (CML), the treatment of choice is bone marrow transplantation.
During the slow progress (chronic phase) of the disease, chemotherapy may be given to try to improve the
cell counts. Radiation therapy, which involves the use
of x rays or other high-energy rays to kill cancer cells
and shrink tumors, may be used in some cases to
reduce the discomfort and pain due to an enlarged
GALE ENCYCLOPEDIA OF MEDICINE

Most cancers can be prevented by changes in lifestyle or diet, which will reduce the risk factors.
However, in leukemias, there are no known risk factors. Therefore, at the present time, there is no way
known to prevent the leukemias from developing.
People who are at an increased risk for developing
leukemia because of proven exposure to ionizing
radiation, the organic liquid benzene, or people who
2207

Leukemias, chronic

KEY TERMS

Leukocytosis

have a history of other cancers of the lymphoid system
(Hodgkin’s lymphoma) should undergo periodic medical checkups.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
Cancer Research Institute. 681 Fifth Ave., New York, N.Y.
10022. (800) 992-2623. <http://
www.cancerresearch.org>.
Leukemia Society of America, Inc. 600 Third Ave., New
York, NY 10016. (800) 955 4572. <http://
www.leukemia.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
Oncolink. University of Pennsylvania Cancer Center.
<http://cancer.med.upenn.edu>.

Lata Cherath, PhD

Leukocytosis
Definition
Leukocytosis is a condition characterized by an
elevated number of white cells in the blood.

Description
Leukocytosis is a condition that affects all types of
white blood cells. Other illnesses, such as neutrophilia,
lymphocytosis, and granulocytosis, target specific
types of white blood cells. Normal white blood cell
counts are 4,300-10,800 white blood cells per microliter. Leukocyte or white blood cell levels are considered elevated when they are between 15,000-20,000 per
microliter. The increased number of leukocytes can
occur abnormally as a result of an infection, cancer,
or drug intake; however, leukocytosis can occur normally after eating a large meal or experiencing stress.

Causes and symptoms
Leukemias can cause white blood cell counts to
increase to as much as 100,000. Each kind of white cell
can produce a leukemia. Apart from leukemias, nearly
all leukocytosis is due to one type of white blood cell,
the polymorphonuclear leukocyte (PMN). These conditions are more accurately referred to as neutrophilia.
2208

KEY TERMS
Biopsy—Surgical
removal
of
tissue
for
examination.
Inflammation—Heat, swelling, redness, and pain
caused by tissue injury.
Ketoacidosis—A severe stage of diabetes where
acids and ketones accumulate in the body.
NSAID—Non-steroidal anti-inflammatory drug
such as ibuprofen.

The most common and important cause of neutrophilia is infection, and most infections cause neutrophilia. The degree of elevation often indicates the
severity of the infection. Tissue damage from other
causes raises the white count for similar reasons.
Burns, infarction (cutting off the blood supply to a
region of the body so that it dies), crush injuries,
inflammatory diseases, poisonings, and severe diseases, like kidney failure and diabetic ketoacidosis, all
cause neutrophilia.
Counts almost as high occur in leukemoid
(leukemia-like) reactions caused by infection and
non-infectious inflammation.
Drugs can also cause leukocytosis. Cortisone-like
drugs (prednisone), lithium, and NSAIDs are the most
common offenders.
Non-specific stresses also cause white blood cells
to increase in the blood. Extensive testing of medical
students reveals that neutrophilia accompanies every
examination. Vigorous exercise and intense excitement also cause elevated white blood cell counts.

Diagnosis
A complete blood count (CBC) is one of the first
tests obtained in any medical setting. More than
11,000 white cells in a cubic millimeter of blood is
considered high. Bone marrow biopsy may help clarify
the cause.

Treatment
Relieving the underlying cause returns the count
to normal.

Prognosis
By treating the underlying condition, white blood
cell counts usually return to normal
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Holland, Steven M., and John I. Gallin. ‘‘Disorders of
Granulocytes and Monocytes.’’ In Harrison’s Principles
of Internal Medicine, edited by Anthony S. Fauci, et al.
New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

basis they may help to prevent or control the symptoms of persistent asthma—asthma with symptoms
that last at least two days per week or two nights per
month. They also are prescribed for children with
frequent or more severe asthma attacks and for those
who dislike or have difficulty using asthma inhalers.
Although leukotriene inhibitors may decrease the
need for inhaled beta-agonists or corticosteroids, they
are not used to treat asthma attacks. Leukotriene
inhibitors also may be used to treat symptoms of
allergic rhinitis or short-term seasonal allergies,
including sneezing, runny nose, itching, and wheezing.

Leukotriene inhibitors
Definition
Leukotriene inhibitors are prescription medications that treat asthma and some allergies by blocking
the formation or activity of leukotrienes—small mediator chemicals produced by cells in the body.

Purpose
More than 50 million Americans suffer from
asthma and allergies. Asthma is one of the most prevalent chronic diseases in the United States, affecting
9 million (12.7%) of children. Seasonal allergies affect
20–40 million (20%) of Americans, about 40% of
them children. It is estimated that 60–70% of those
with asthma also suffer from allergic rhinitis, allergies
affecting the mucous membranes of the nose.
Asthma, an inflammation of the bronchial airways, and seasonal allergies and allergic rhinitis
involve several chemical mediators including histamine and leukotrienes. Leukotrienes are a class of
unsaturated fatty-acid chains containing 20 carbon
atoms.
During an asthma attack or within minutes of
exposure to an allergen such as dust or pollen, leukotrienes are released by a type of blood cell in the lungs,
causing the following responses:


contraction of the bronchial airway muscles



inflammation of the airway linings



swelling and narrowing of the airways



production of mucus and fluid



wheezing and shortness of breath



nasal congestion

Leukotriene inhibitors may decrease the symptoms of mild to moderate allergen-induced asthma,
improve nighttime symptoms, and reduce the number
of acute asthma attacks. Taken daily on a long-term
GALE ENCYCLOPEDIA OF MEDICINE

Description
Leukotriene
leukotriene:

inhibitors



blockers



modifiers



antagonists



pathway modifiers

are

often

called

When they were first introduced in 1996, leukotriene inhibitors represented the first new class of
asthma medication in two decades. Classified as antiinflammatories, they were originally developed to
improve lung function in asthmatics by relaxing the
smooth muscles around the bronchial airways and by
reducing lung inflammation.
Types of leukotriene inhibitors
The available leukotriene inhibitors are: montelukast (Singulair), zafirlukast (Accolate), and zileuton
(Zyflo).
Montelukast and zafirlukast are leukotrienereceptor antagonists that prevent leukotriene from
binding to cell receptors and initiating the chain of
events leading to symptoms of allergy and asthma.
Montelukast works rapidly. It is the only leukotriene
inhibitor that has been approved by the U.S. Food and
Drug Administration (FDA) for use in children as
young as two, as well as for the treatment of seasonal
allergies.
Zafirlukast is a synthetic peptide that inhibits the
receptor binding of three leukotreines (LTC4, LTD4,
and LTE4) that cause smooth muscle constriction. It is
used for mild to moderate persistent asthma, exerciseinduced asthma, and the management of allergic rhinitis in those aged seven and older.
Zileuton is a 5-lipooxygenase pathway inhibitor
that interferes with the synthesis of LTA4, LTC4,
2209

Leukotriene inhibitors

Resources

Leukotriene inhibitors

LTD4, and LTE4. It is used to treat chronic asthma in
adolescents and adults.
Effectiveness
Leukotriene inhibitors may be prescribed along
with inhaled corticosteroids for control of mild to
moderate, persistent asthma. Used alone they are
less effective than low-dose inhaled corticosteroids.
However, they enable some people to reduce their
doses of inhaled corticosteroids. Leukotriene inhibitors may be an option for people with mild asthma
who want to avoid corticosteroids, which can cause
serious side effects with long-term use. When used in
conjunction with beta-agonists, leukotriene inhibitors reduce symptoms and may lower the betaagonist usage.
Leukotriene inhibitors appear to decrease the
symptoms of seasonal allergic rhinitis. Although they
may relieve nasal congestion better than antihistamines, they are less effective than corticosteroid nasal
sprays. A leukotriene inhibitor combined with an antihistamine may be more effective than either drug
alone.
Leukotriene inhibitors have helped some children
who suffer from nocturnal asthma, exercise- and
aspirin-induced asthma, allergic rhinitis, and seasonal
allergies.

asthma flare-up by 32% as compared with a control
group receiving a placebo. Singulair also delayed the
onset of the first asthma flare-up and reduced the need
for inhaled medication. However, it did not reduce the
length or severity of the flare-up once it had begun.
The researchers suggested that children with infectiontriggered asthma should begin taking a leukotriene
inhibitor before the start of the flu season or at the
onset of an upper-respiratory-tract infection.
Another 2005 study found that children whose
asthma improved with montelukast alone were younger
and had had asthma for a shorter period of time as
compared with children whose asthma improved only
with inhaled corticosteroids. Among the children whose
lung function improved by at least 7.5%, 5% took
montelukast alone, 23% were on inhaled corticosteroids only, and 17% were on both medications.
Other uses
Leukotriene inhibitors have been used successfully to treat inflammations of the esophagus (esophagitis) or stomach and intestines (gastroenteritis) that
are caused by white blood cells called eosinophils that
are involved in allergic reactions. Montelukast has
been used to successfully treat symptoms of interstitial
cystitis, a chronic inflammation of the bladder.

Recommended dosage
Clinical studies
Montelukast appears to be an effective asthma
controller in about one-third of patients. Another
one-third receives no benefit. However, most longterm studies have found that standard inhaled corticosteroids are more effective for controlling
asthma than either beta-agonists or leukotriene
inhibitors.
A 2003 analysis of 13 clinical studies found that
Singulair and Accolate resulted in 60% more asthma
flare-ups and other symptoms as compared with traditional asthma treatments. Patients using inhaled
corticosteroids had fewer daytime symptoms and
night awakenings than those taking Singulair or
Accolate. The researchers advised against switching
to a leukotriene inhibiter unless the dosage
of inhaled medication is less than 400 micrograms
per day.
A 2005 study sponsored by Merck, the maker of
Singulair, found that a one-year course of Singulair
was useful for treating two- to five-year-olds with
occasional asthma attacks that were triggered by
respiratory infections. Singulair reduced this type of
2210

Montelukast is taken once per day in the evening
so as to relieve morning allergy symptoms. Although
dosing may vary, average daily doses of montelukast
for asthma and seasonal allergies are: children aged
1–5: one 4-mg chewable tablet or 4-mg oral granules
(one packet), swallowed whole or mixed in a spoonful of soft food; children aged 6–14: one 5-mg chewable tablet; children over 14 and adults: one 10-mg
tablet.
The average doses of zafirlukast for children aged
7–11 are 10-mg tablets twice a day. Children aged 12
and older and adults usually take 20-mg tablets twice a
day. Zafirlukast is taken one hour before or two hours
after a meal, since food reduces its bioavailability by
about 49%.
The average dose of zileuton is a 600-mg tablet
four times per day for children aged 12 and older and
adults.
Leukotriene inhibitors are expensive. Missed
doses should be taken as soon as possible unless it is
almost time for the next dose, in which case the dose
should be skipped.
GALE ENCYCLOPEDIA OF MEDICINE



abdominal pain

Although leukotriene inhibitors are considered
safe, they can raise the levels of liver enzymes. The
FDA recommends liver function tests monthly for the
first three months on medication, followed by quarterly monitoring for the next year, and continued
interim testing. Zileuton is contraindicated for those
with elevated liver enzymes, active alcoholism, or liver
disease. Increased levels of liver enzymes may be
detectable in the blood within two months of starting
zileuton. Zileuton can affect liver function and, one
rare occasions, can damage the liver.



nausea and vomiting



diarrhea

It is unclear whether leukotriene inhibitors should
be taken during pregnancy. Zafirlukast and zileuton
should not be used by a woman who is breastfeeding.
Both medications have been found to increase the risk
of mild to moderate respiratory tract infections in
patients aged 55 and older.
Medical conditions that may interfere with the use
of montelukast include: allergies to aspirin or nonsteroidal anti-inflammatories (NSAIDs); liver disease,
which can increase the blood levels of the drug; and
phenylketonuria because chewable tablets may contain
aspartame.
A healthcare provider should be contacted if an
increased number of short-acting bronchodilator
inhalations are needed to relieve an acute asthma
attack or if more than the maximum number of daily
inhalations are required while using zileuton.
To be effective montelukast and zafirlukast must
be taken at the same time every day. Zileuton must be
taken at regularly spaced intervals every day, even if
asthma symptoms appear to improve. Montelukast
should be continued through an acute asthma attack
in addition to rescue medication.

Side effects
Although leukotriene inhibitors generally have few
side effects and those may subside as the body adjusts to
the drug, headaches are common with these medications. Headaches occur in 18–19% of those taking
montelukast and in 25% of those taking zileutin.
Among 7 to 11 year olds on zanfirlukast, 4.5% suffer
from headaches, as do 12.9% of those aged 12 and over.
Other less common side effects of leukotriene
inhibitors include:

Montelukast appears to cause fewer side effects
than other leukotriene inhibitors and is less likely to
affect the liver. Side effects occurring in less than 4.2%
of patients include:


heartburn



weakness



fever



nasal congestion



cough



dental pain



rarely, pus in the urine
Rare side effects of zileuton include:



itching



flu-like symptoms



upper right abdominal pain



yellow eyes or skin (jaundice)

Interactions
Drugs that may interact with montelukast
include:


aspirin



NSAIDs



phenobarbital



rifampin

Zafirlukast and zileuton can raise the blood levels
of the asthma medication theophylline (Theo Dur and
others) and the blood thinner warfarin (Coumarin).
Theophylline levels and blood-clotting times should
be monitored frequently.
Medications that may interact with zafirlukast
include:


aspirin



blood pressure medications



some seizure medications

Medications that may interact with zileuton
include:



rash



the beta-blocker propanolol



fatigue



beta-agonists



dizziness



terfenadine (Seldane and others)

GALE ENCYCLOPEDIA OF MEDICINE

2211

Leukotriene inhibitors

Precautions

Lice infestation

KEY TERMS

Evidence.’’ British Medical Journal 236, no. 7390
(March 22, 2003): 621–6.
ORGANIZATIONS

Allergic rhinitis—Nasal symptoms caused by an
allergic reaction.
Asthma—A disease that causes the bronchial airways to narrow, swell, and produce mucus, making
breathing difficult.
Beta-agonist—Beta2-agonist; beta-adrenergic agonist; a bronchodilator medication—inhaled or oral—
that relaxes the muscles surrounding the airways
to relieve asthma symptoms.
Corticosteroids—Inhaled medications for longterm control of asthma.
Leukotrienes—A class of small molecules produced by cells in response to allergen exposure;
they contribute to allergy and asthma symptoms.
Montelukast (Singulair)—An inhibitor that prevents leukotrienes from binding to cell receptors;
taken over time, montelukast can reduce or prevent
symptoms of asthma and allergies.
Zafirlukast (Accolate)—An inhibitor that prevents
leukotrienes from binding to cell receptors; taken
over time, zafirlukast can help reduce or prevent
asthma symptoms.
Zileuton (Zyflo)—A medication that interferes with
the biosynthetic pathway that produces leukotrienes; used to help prevent asthma attacks.

American Academy of Allergy, Asthma and Immunology.
555 East Wells Street, Suite 1100, Milwaukee, WI
53202-3823. (800)822-2762. <http://www.aaaai.org>.
Childhood Asthma Research and Education (CARE)
Network. National Heart, Lung, and Blood Institute.
6701 Rockledge Drive, MSC 7952, Bethesda, MD
20892-7952. (301) 435-0202. <http://www.asthmacarenet.org>.
OTHER

Lehnert, Paul. ‘‘Leukotriene Modifiers for Allergic
Rhinitis.’’ Health Guide A-Z. WebMD. October 8, 2003
[cited March 14, 2005]. <http://my.webmed.com/hw/
allergies/ug2390.asp>.
———. ‘‘Leukotriene Pathway Modifiers for Asthma.’’
Health Guide A-Z. WebMD. March 5, 2004 [cited
March 14, 2005]. <http://my.webmed.com/hw/
asthma/hw163553.asp>.
Mayo Clinic Staff. ‘‘Medications and Immunotherapy for
Asthma.’’ Asthma Center. MayoClinic.com. August 13,
2004 [cited March 14, 2005]. <http://
www.mayoclinic.com/invoke.cfm?objectid=
58BCFCCC-BB00-4E67-A29876A9D30B65ED>.

Margaret Alic, Ph.D.

Levodopa see Antiparkinson drugs
Levothyroxine see Thyroid hormones
LGV see Lymphogranuloma venereum

Resources
BOOKS

Haughney, John. Leukotriene Receptor Antagonists:
Evidence and Experience Examined. London: Royal
Society of Medicine Press, 2001.
Sampson, A. P., and S. T. Holgate. Leukotriene Modifiers in
Asthma Treatment. London: Martin Dunitz, 1999.
PERIODICALS

‘‘Asthma: Corticosteroids Are More Effective than BetaAgonists or Leukotriene Antagonists.’’ Health &
Medicine Week (December 20, 2004): 77.
‘‘Asthma: Journal Publishes Research on Tailoring Asthma
Treatment in Children.’’ Health & Medicine Week
(February 28, 2005): 75.
Banasiak, Nancy Cantey, and Mikki Meadows-Oliver.
‘‘Leukotrienes: Their Role in the Treatment of Asthma
and Seasonal Allergic Rhinitis.’’ Pediatric Nursing 31,
no. 1 (January/February 2005): 35–8.
Ducharme, F. M. ‘‘Inhaled Glucocorticoids Versus
Leukotriene Receptor Antagonists as Single Agent
Asthma Treatment: Systematic Review of Current

2212

Lice infestation
Definition
Lice infestations (pediculoses) are infections of the
skin, hair, or genital region caused by lice living
directly on the body or in hats or other garments.
Lice are small wingless insect-like parasites with sucking mouthparts that feed on human blood and lay
their eggs on body hairs or in clothing. The name
pediculosis comes from the Latin word for louse
(singular) or lice (plural). Some anthropologists
believe that the different species of head and body
lice developed in response to humans’ invention and
use of clothing about 50,000 years ago.

Description
Lice infestations are not dangerous infections by
themselves. It is, however a serious public health
GALE ENCYCLOPEDIA OF MEDICINE

Lice infestations are frequent occurrences in areas
of overcrowding or inadequate facilities for bathing
and laundry. They are often associated with homelessness in the general population or with military,
refugee, or prisoner camps in war-torn areas. All
humans are equally susceptible to louse infestation;
the elderly, however, are more vulnerable to typhus
and other diseases carried by lice.

Lice infestation

problem because some lice can carry organisms that
cause other diseases, including relapsing fever, trench
fever, and epidemic typhus. Although trench fever is
self-limiting, the other two diseases have mortality
rates of 5%–10%. Pubic lice are often associated
with other sexually transmitted diseases (STDs) but
do not spread them.

This woman’s eyelashes are infested with nits, or eggs, of a
body louse. (Custom Medical Stock Photo. Reproduced by
permission.)

Causes and symptoms
The symptoms of lice infestations vary somewhat
according to body location, although all are characterized by intense itching, usually with injury to the
skin caused by scratching or scraping. The itching is an
allergic reaction to a toxin in the saliva of the lice.
Repeated bites can lead to a generalized skin eruption
or inflammation.
Head lice
This type of infestation is caused by Pediculosis
humanus capitis, the head louse. Head lice can be
transmitted from one person to another by the sharing
of hats, combs, or hair brushes. Epidemics of head
lice are common among school-age children from all
class backgrounds in all parts of the United States.
The head louse is about 1/16 of an inch in length.
The adult form may be visible on the patient’s scalp,
especially around the ears; or its grayish-white nits
(eggs) may be visible at the base of the hairs close to
the scalp. It takes between three and 14 days for the
nits to hatch. After the nits hatch, the louse must feed
on blood within a day or die.
Head lice can spread from the scalp to the
eyebrows, eyelashes, and beard in adults, although
they are more often limited to the scalp in children.
The itching may be intense, and may be followed by
bacterial infection of skin that has been scratched
open. Another common complication is swelling or
inflammation of the neck glands. Head lice do not
spread typhus or other systemic diseases.
Body lice
Infestations of body lice are caused by Pediculosis
humanus corporis, an organism that is similar in size to
GALE ENCYCLOPEDIA OF MEDICINE

head lice. Body lice, however, are rarely seen on the
skin itself because they come to the skin only to feed.
They should be looked for in the seams of the patient’s
clothing. This type of infestation is associated by
wearing the same clothing for long periods of time
without laundering, as may happen in wartime or in
cold climates; or with poor personal hygiene. It can be
spread by close personal contact or shared bedding.
Patients with body lice often have intense itching
with deep scratches around the upper shoulders, flanks,
or neck. The bites first appear as small red pimples
but may cause a generalized skin rash. If the infestation
is not treated, the patient may develop complications
that include headache, fever, and bacterial infection
with scarring. Body lice can spread systemic typhus or
other infections.
Pubic lice
Pubic lice are sometimes called ‘‘crabs.’’ This type
of infestation is caused by Phthirus pubis and is
commonly spread by intimate contact. People can
also get pubic lice from using the bedding, towels, or
clothes of an infected person.
Pubic lice usually appear first on pubic hair, but
may spread to other parts of the body, particularly if
the patient is very hairy. Pubic lice are also sometimes
seen on the eyelashes of children born to infected
mothers. It is usually easier for the doctor to see
marks from the patient’s scratching than the bites
from the lice, but pubic lice sometimes produce small
bluish spots called maculae ceruleae on the patient’s
trunk or thighs. Pubic lice also sometimes leave small
dark brown specks from their own excreted matter on
the parts of the patient’s underwear that cover the anal
or genital areas.
2213

Lice infestation

Diagnosis
Doctors can diagnose lice infestations from looking closely at the parts of the body where the patient has
been scratching. Lice are large enough to be easily seen
with the naked eye or a magnifying glass. The eggs of
pubic lice as well as head lice can often be found by
looking at the base of the patient’s hairs. Pediatricians
are most likely to diagnose lice in school-age children.
It is important for doctors to rule out other diseases
that can cause scratching and skin inflammation
because the medications used to kill lice are very strong
and can have bothersome side effects. The doctor will
need to distinguish between head lice and dandruff;
between body lice and scabies (a disease caused by
skin mites); and between pubic lice and eczema.
Blood tests or other laboratory tests are not useful
in diagnosing lice infestations.

A close-up view of a body louse. (Custom Medical Stock Photo.
Reproduced by permission.)

Patients with pubic lice should be examined and
tested for other STDs.

Treatment
Cases of head lice are usually treated with shampoos or rinses containing either lindane (Kwell) or
permethrin (Nix). Permethrin is considered preferable,
however, because lindane is absorbed through the skin
and may produce symptoms of neurotoxicity. The person applying the treatment should wear rubber gloves
and rinse the patient’s hair or body completely after
use. Following the treatment, nits should be removed
from the hair with a fine-toothed comb or tweezers.
Lindane is also effective for treating infestations of
body or pubic lice, but it should not be used by pregnant women. In most cases one treatment is sufficient,
but the medication can be reapplied a week later if
living lice have reappeared.
Another drug that appears to be effective in treating lice is ivermectin (Stromectol), a strong antiparasite
drug that is usually given to treat intestinal worms. Two
doses of the drug, however, cured 99% of cases of head
lice as well as intestinal worms in a poor population
with high rates of infestation with both types of
parasites.
Infestations of body lice can also be treated by
washing the patient’s clothes or bedding in boiling
water, ironing seams with an iron on a high setting,
or treating the clothes with 1% malathion powder or
10% DDT powder.
If the patient’s eyelashes have been infested, the
only safe treatments are either a thick coating of petroleum jelly (Vaseline) applied twice daily for eight days,
or 1% yellow oxide of mercury applied four times a day
for two weeks. Any remaining nits should be removed
with tweezers.
2214

Alternative treatment
For pubic lice, some practitioners of holistic medicine recommend a mixture of 25% oil of pennyroyal
(Mentha pulegium), 25% garlic (Allium sativum) oil,
and 50% distilled water applied three times in a threeday period, followed by removal of dormant eggs to
prevent reinfestation.
Another alternative treatment for head lice is tea
tree oil, sometimes called melaleuca oil. Tea tree oil
appears to work well in treating head lice that have
developed resistance to other preparations.

Prognosis
Lice can be successfully eradicated in almost
all cases, although a growing number of cases of
drug-resistant lice have been reported. As of 2004,
some researchers are concerned about the rapid but
unpredictable spread of these resistant lice. Ovide,
a newer medication containing malathion, appears
to be effective in treating patients with permethrinresistant lice.
In general, patients are more at risk from typhus,
trench fever, rickettsial infections, and other diseases
spread by lice than from the lice themselves.

Prevention
There are no vaccines or skin treatments that will
protect a person against lice prior to contact. In addition, lice infestation does not provide immunity against
reinfection; recurrences are in fact quite common.
GALE ENCYCLOPEDIA OF MEDICINE

Crabs—An informal or slang term for pubic lice.
Lindane—A benzene compound that is used to kill
body and pubic lice. Lindane works by being
absorbed into the louse’s central nervous system,
causing seizures and death.
Maculae ceruleae—Bluish or blue-grey skin eruptions often seen on the trunk or thighs of patients
with pubic lice. The Latin words mean blue spots.
Malathion—An insecticide that can be used in
1% powdered form to disinfect the clothes of
patients with body lice.
Nits—The eggs produced by head or pubic lice,
usually grayish-white in color and visible at the
base of hair shafts.
Pediculosis (plural, pediculoses)—The medical
term for infestation with lice.
Permethrin—A medication used to rid the scalp of
head lice. Permethrin works by paralyzing the lice,
so that they cannot feed after hatching within the
24 hours required for survival.

Eradication of Bartonella quintana from Blood in
Patients with Chronic Bacteremia.’’ Antimicrobial
Agents and Chemotherapy 47 (July 2003): 2204–2207.
Heukelbach, J., and H. Feldmeier. ‘‘Ectoparasites—The
Underestimated Realm.’’ Lancet 363 (March 13, 2004):
889–891.
Heukelbach, J., T. Wilcke, B. Winter, et al. ‘‘Efficacy of
Ivermectin in a Patient Population Concomitantly
Infected with Intestinal Helminths and Ectoparasites.’’
Arzneimittelforschung 54 (2004): 416–421.
Hunter, J. A., and S. C. Barker. ‘‘Susceptibility of Head Lice
(Pediculus humanus capitis) to Pediculicides in
Australia.’’ Parasitology Research 90 (August 2003):
476–478.
Kittler, R., M. Kayser, and M. Stoneking. ‘‘Molecular
Evolution of Pediculus humanus and the Origin of
Clothing.’’ Current Biology 13 (August 19, 2003):
1414–1417.
Mills, C., B. J. Cleary, J. F. Gilmer, and J. J. Walsh.
‘‘Inhibition of Acetylcholinesterase by Tea Tree Oil.’’
Journal of Pharmacy and Pharmacology 56 (March
2004): 375–379.
Yoon, K. S., J. R. Gao, S. H. Lee, et al. ‘‘PermethrinResistant Human Head Lice, Pediculus capitis, and
Their Treatment.’’ Archives of Dermatology 139
(August 2003): 1061–1064.
ORGANIZATIONS

Prevention depends on adequate personal hygiene at
the individual level and the following public health
measures:


Teaching school-age children the basics of good
personal hygiene, including the importance of not
lending or borrowing combs, brushes, or hats.



Notifying and treating an adult patient’s close personal and sexual contacts.



Examining homeless people, elderly patients incapable
of self-care, and other high-risk individuals prior to
hospital admission for signs of louse infestation. This
measure is necessary to protect other hospitalized
people from the spread of lice.

Resources

American Academy of Dermatology (AAD). 930 East
Woodfield Road, Schaumburg, IL 60173. (847)
330-0230. <http://www.aad.org>.

Rebecca J. Frey, PhD

Lichen planus
Definition
Lichen planus is a skin condition of unknown
origin that produces small, shiny, flat-topped, itchy
pink or purple raised spots on the wrists, forearms or
lower legs, especially in middle-aged patients.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Pediculosis.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Downs, A. M. ‘‘Managing Head Lice in an Era of Increasing
Resistance to Insecticides.’’ American Journal of
Clinical Dermatology 5 (March 2004): 169–177.
Foucault, C., D. Raoult, and P. Brouqui. ‘‘Randomized
Open Trial of Gentamicin and Doxycycline for
GALE ENCYCLOPEDIA OF MEDICINE

Description
Lichen planus affects between 1-2% of the population, most of whom are middle-aged women. The
condition is less common in the very young and
the very old. The lesions are found on the skin,
genitals, and in the mouth. Most cases resolve spontaneously within two years. Lichen planus is found
throughout the world and is equally distributed
among races.
2215

Lichen planus

KEY TERMS

Lichen planus

KEY TERMS
PUVA—A type of phototherapy that combines the
oral or topical photosensitizing chemical psoralen,
plus long-wave ultraviolet light-A (UVA).

One example of lichen planus on the tongue. (Custom Medical
Stock Photo. Reproduced by permission.)

Causes and symptoms
No one knows what causes lichen planus,
although some experts suspect that it is an abnormal
immune reaction following a viral infection, probably aggravated by stress. The condition is similar
to symptoms caused by exposure to arsenic, bismuth,
gold, or developers used in color photography.
Occasionally, lichen planus in the mouth appears
to be an allergic reaction to medications, filling
material, dental hygiene products, chewing gum or
candy.
Symptoms can appear suddenly, or they may
gradually develop, usually on the arms or legs. The
lesions on the skin may be preceded by a dryness and
metallic taste or burning in the mouth.
Once the lesions appear, they change over time
into flat, glistening, purple lesions marked with white
lines or spots. Mild to severe itching is common.
White, lacy lesions are usually painless, but eroded
lesions often burn and can be painful. As the lesions
clear up, they usually leave a brown discoloration
behind, especially in dark skinned people.
Lichen planus in the mouth occurs in six different
forms with a variety of symptoms, appearing as lacywhite streaks, white plaques, or eroded ulcers. Often
the gums are affected, so that the surface of the gum
peels off, leaving the gums red and raw.

Diagnosis
A doctor can probably diagnose the condition
simply from looking at the characteristic lesions,
but a skin biopsy may be needed to confirm the
diagnosis.
2216

Lichen planus appearing under the tongue. (Custom Medical
Stock Photo. Reproduced by permission.)

Treatment
Treatment is aimed at easing symptoms. Itching
can be treated with steroid creams and oral antihistamines. Severe lesions can be treated with corticosteroids
by mouth, or combinations of photochemotherapy
(PUVA) and griseofulvin.
Patients with lesions in the mouth may find that
regular professional cleaning of the teeth and conscientious dental care improve the condition. Using
milder toothpastes instead of tartar control products
also seems to lessen the number of ulcers and makes
them less sensitive.

Prognosis
While lichen planus can be annoying, it is usually
fairly benign and clears up on its own. It may take
months to reach its peak, but it usually clears up
within 18 months.
Resources
OTHER

Lichen Planus Self-Help. Baylor College of Dentistry.
<http://www.tambcd.edu/lichen>.

Carol A. Turkington
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Lichen simplex chronicus is a chronic inflammation
of the skin (dermatitis) characterized by small, round
itchy spots that thicken and become leathery as a result
of scratching.

Description
Also termed neurodermatis, lichen simplex chronicus is the result of chronic skin irritation. It occurs in
4-5 out of every thousand people. Initial irritation
causes itching, and in turn, itching causes scratching.
Scratching leads to further irritation, which damages
the skin. The possibility of infection is greatly
increased when the outer layer of protective skin is
broken. Skin usually repairs itself quickly; however,
in the case of lichen simplex chronicus, healing skin
causes more itching and more scratching causes a
thickening of the skin (lichen). The small skin patches
are usually 1–10 in (2.54–25.4 cm) in diameter.

Causes and symptoms
Lichen simplex chronicus is often caused by
constant rubbing of the skin. The rubbing begins
the chain of events that leads from itching to scratching and then to the presence of leather-like skin
patches.
Symptoms are chronic itching which is often
accompanied by nervous tension. The appearance of
scratch marks and the leathery skin patches can be
found anywhere on the body. A prolonged lichen
simplex chronicus can result in brown-colored pigmentation at the site of irritation.

Antihistamine—A chemical that interferes with the
action of histamine. Histamine is part of an inflammatory response and helps to cause itching.
Callus—Thickened skin due to chronic rubbing or
irritation.
Lesion—Abnormal change in tissue caused by
localized disease.

Among the topical medications that relieve itching are a number of commercial preparations containing menthol, camphor, eucalyptus oil, and aloe.
Topical cortisone is also available without a prescription. Some preparations also contain antihistamines,
which penetrate intact skin poorly. All these medicines
work better under occlusion, which means putting a
waterproof barrier like a rubber glove or plastic wrap
over them. For broken skin, topical antibiotics like
bacitracin help prevent infection. These should be
used early to forestall further damage to the skin.
Reducing the buildup of thick skin may require
medicines that dissolve or melt keratin, the major
chemical in skin’s outer layer. These keratolytics
include urea, lactic acid, and salicylic acid.
Resistant cases of lichen simplex chronicus will
often respond to cortisone-like drugs injected directly
into the lesions.
Sedatives or tranquilizers may be prescribed to
combat the nervous tension and anxiety that often
accompanies the condition.

Prognosis
Diagnosis
A dermatologist, a physician specializing in the
study and treatment of skin disorders, can make a
diagnosis after a visual exam.

Treatment
Treatment of the itching is necessary to stop the
scratching and resulting skin damage. There are a
number of ways to stop itching. Perhaps the most
important is to cut fingernails very short. Ice can substitute for the relief of scratching. Heat and fuzzy
clothing worsen itching; cold and smooth clothing
pacify it. If the itching is persistent, dressings may be
applied to the affected areas.
GALE ENCYCLOPEDIA OF MEDICINE

Diligent adherence to treatment is usually
rewarded with a resolution of the condition. The
original cause of itching may be gone, or it may
reappear. Preventive treatment in its early stages
will arrest the process.

Prevention
Early, gentler substitutes for scratching can
entirely prevent lichen simplex chronicus.
Resources
BOOKS

Swerlick, Robert A., and Thomas J. Lawley. ‘‘Eczema,
Psoriasis, Cutaneous Infections, Acne, and Other
2217

Lichen simplex chronicus

KEY TERMS

Lichen simplex chronicus

Life support

Common Skin Disorders.’’ In Harrison’s Principles of
Internal Medicine, edited by Anthony S. Fauci, et al.
New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Life support
Definition
Life support refers to a spectrum of techniques
used to maintain life after the failure of one or more
vital organs.

Life support may begin with basic cardiopulmonary resuscitation (CPR), as in cases of cardiac arrest.
Thereafter, the most common technique used to create
a secure airway is insertion of an endotracheal (ET)
tube through the mouth or nose into the windpipe
(trachea). An alternative method of securing an airway is by tracheotomy, a surgical procedure in which a
tube is inserted into the trachea through an incision
made in the base of the throat. Of the two options,
placement of an ET tube is usually quicker and more
convenient, and thus occurs much more commonly.
Doctors perform a tracheotomy when they cannot establish an ET airway, or when the patient will
require an artificial airway for more than a week or
two.
Breathing refers to the movement of air in and out
of the lungs. Inadequate breathing may result from:


Heart disease, as in congestive heart failure

A patient requires life support when one or more
vital organs fail, due to causes such as trauma, infection, cancer, heart attack, or chronic disease. Among
the purposes of life support are to:



Primary disease of the lungs, such as pneumonia,
asthma, or emphysema



Coma of any cause, such as narcotic overdose or
stroke



Establish and maintain the ABC’s of resuscitation—
airway, breathing, and circulation.



Muscle fatigue or neuromuscular disease (spinal cord
injury or polio)



Restore the patient’s homeostasis—the internal
chemical and physical balance of the body.



Pain, from rib fractures or surgery on the chest

Purpose



Protect the patient from complications of the underlying disease and its treatment.

Precautions
Patients and families need to recognize that life
support is an extremely painful, expensive, and emotionally wrenching experience. Life support exposes a
patient to vast risks of further medical complications,
and offers no guarantee of a positive outcome. Even in
successful cases, recovery may be slow and frustrating.

Description
Successful life support begins with establishing
the ABC’s of resuscitation—airway, breathing, and
circulation.
The airway refers to a clear passageway for air to
enter the lungs from outside the body. The patient’s
airway may become blocked by:


Foreign body obstruction, as by food or dentures



Injury-related damage and swelling, as from a wound
or surgery



Loss of protective reflexes due to coma of any origin

2218

When the patient cannot breathe sufficiently, the
physician will use a ventilator, a machine that pumps
air in and out of the patient’s lungs. For many doctors
and members of the public, the term ‘‘life support’’
calls up the image of an ET tube and ventilator.
Circulation refers to the flow of blood around the
body from the heart to vital organs. Circulation can
fail due to:


Primary disease of the heart (heart attack)



Blood loss (trauma or internal bleeding of any cause)



Severe infection (sepsis)



Drug reactions or overdoses



Extreme allergic reaction



Severe dehydration (gastroenteritis or heat-related
illness)

In order to ensure adequate circulation, the
patient will require one or more intravenous (IV)
tubes (catheters). The IVs may include both the short
needle and tube commonly used in the hand or forearm, and longer catheters inserted into the larger and
more central veins of the body. Catheters inserted into
these larger veins are known as central lines. Through
the IVs the patient receives fluids, drugs, and blood
transfusions as needed to support the circulation.
GALE ENCYCLOPEDIA OF MEDICINE



Drugs to improve circulation and other body
functions



Antibiotics



Transfusions



Surgery



Nutritional supplements by vein or stomach tube

Preserving the body’s internal equilibrium
requires careful monitoring of innumerable indicators
of the patient’s well-being. These indicators include:



Tubes in body cavities (chest or abdomen) to relieve
fluid buildup



Dialysis



Pacemaker



Electrical defibrillation



Various machines to assist heart or lung function



Transplantation of organs or mechanical substitutes
(artificial heart)



Sedation or even temporary paralysis to enable the
patient to tolerate these procedures



Vital signs (heartbeats per minute, breaths per minute, blood pressure, body temperature, and weight)



Fluids (input and output of the body)



Blood cell counts



Chemical substances of the body (sodium, potassium,
sugar, and many others)



Pressures in the circulation, lungs, and perhaps even
the brain



Presence of germs (bacteria, fungi) causing infection
in body systems (lungs, blood, urine)

This intensive monitoring usually takes place in
an intensive care unit (ICU) or critical care unit (CCU)
and requires:


Specialized physicians, such as cardiologists, intensivists, and surgeons



Highly-skilled nursing care, often one nurse per
patient around-the-clock



Extensive support staff, such as respiratory therapists, laboratory technicians, radiology technicians,
dieticians, and pharmacists



Constant measurement of basics such as pulse, heart
rhythm, and oxygen level in the blood



Frequent inspection of the patient’s alertness, color,
and level of pain



Use of catheters in the veins and arteries to withdraw
blood samples and measure pressures in the circulation



Use of tubes in the bladder (Foley catheter), stomach
(nasogastric tube), and other body cavities



Frequent laboratory tests on blood, urine, drainage
from wounds, and other body specimens



X-ray, ultrasound, computerized tomography (CT),
and other imaging procedures



Electrocardiograms
The treatments of life support include:



Oxygen



Intravenous fluids with sugar and basic salts

GALE ENCYCLOPEDIA OF MEDICINE

Preparation
The need for life support may arise suddenly and
with little warning. All people should discuss in
advance with family and doctor their wishes for the
use of life support should a medical crisis develop. The
doctor will note the preferences in the patient’s record.
Patients should sign documents such as an Advance
Directive and Durable Power of Attorney for Health
Care to express their wishes and designate a surrogate
decision-maker in case of incapacitation.
Physicians and medical care providers must
anticipate the possibility that a patient will require
life support, perhaps suddenly. In preparation, doctors
and medical staff must:


Receive training in resuscitation skills



Monitor patients carefully



Maintain proper supplies and equipment



Discuss in advance with patients and patients’
families whether or not to begin life support

Aftercare
If a patient survives life support treatments, doctors will cautiously try to wean the patient from the
support systems. Being able to breathe adequately
without the ventilator is one major hurdle. Patients
commonly fail in their first attempts to breathe on
their own, often tiring out after a few hours. Thus,
the doctor will reconnect the ventilator, give the
patient a rest, and try again in a day or two.
2219

Life support

Once the ABC’s are secure, life support is directed
at maintaining homeostasis, the body’s delicate
chemical and physical balance. In a healthy person,
the body keeps precise control over many components
of its makeup, such as its fluids, nutrients, and pressures. When vital organs fail, the body can no longer
regulate these components, and the doctor must take
steps to restore the normal state.

Life support

As the patient regains organ function, there is less
need for monitors, tests, and treatments that require
an intensive care setting. The doctor may transfer the
patient to a lower level of hospital care, a skilled nursing facility (SNF), or perhaps directly to home.
Physical and occupational therapists may help the
patient improve strength and endurance. The patient
will receive continuing care from the primary doctor
and specialists as needed. The patient may require
prescription drugs, assist devices, and psychological
therapists.

Risks
The risks and consequences of life support are
enormous. These risks include:

KEY TERMS
Cardiopulmonary—Relating to the heart and lungs.
Central line—A tube placed by needle into a large,
central vein of the body.
Coma—Unconsciousness.
Defibrillation—Use of an electric shock to restore
a normal heartbeat.
Endotracheal tube—A tube placed into the windpipe through the nose or mouth.
Foley catheter—A tube that drains urine from the
bladder.



Physical dangers



Emotional suffering

Homeostasis—The internal chemical and physical
balance of the body.
Nasogastric tube—A tube placed through the nose
into the stomach.



Financial costs

Neuromuscular—Relating to nerves and muscles.



Societal discord

Resuscitation—Treatments to restore an adequate
airway, breathing, and circulation.

The physical dangers of life support encompass all
the hazards of the patient’s underlying disease and
treatments. Among these risks are:


Permanent damage to the brain, kidneys, and other
vital organs caused by poor circulation or low oxygen content of the blood



Direct damage to organs from use of medical instruments and procedures



Infections, often with organisms that are highly
resistant to antibiotics



Abnormal blood clots



Skin ulcers from lying immobilized for long periods



Extreme pain



Exposure of medical personnel to communicable
diseases

The emotional consequences of life support touch
patients, families, and medical caregivers. These repercussions arise from:


The frightening environment of an ICU



The need to make life-and-death decisions



The anger, guilt, and grief that relate to life-threatening illness



The fact that many lengthy and difficult treatments
will end in failure

The financial costs of life support are huge.
A single day of life support costs many thousands of
dollars. These expenses fall on individual payers,
insurance companies, health plans, and governments.
2220

Sepsis—An overwhelming infection with effects
throughout the body.
Tracheotomy—A surgical procedure in which a
tube is inserted into the trachea through an incision
made in the base of the throat.
Trauma—Serious physical injury.
Ventilator—A machine that pumps air in and out of
the lungs.
Vital signs—Basic indicators of body function,
usually meaning heartbeats per minute, breaths
per minute, blood pressure, body temperature,
and weight.

All such payers face difficult decisions regarding the
allotment of money for such treatment, especially in
cases that are likely to be futile.
Society as a whole faces difficult decisions surrounding life support. Some governments have
enacted regulations that establish priorities for the
spending of health care resources. Patients who do
not receive treatment under such rules may feel victimized by society’s choices.
Resources
BOOKS

Irwin, Richard S., Frank B. Cerra, and James M. Rippe,
editors. Irwin and Rippe’s Intensive Care Medicine.
Philadelphia: Lippincott-Raven, 1999.
GALE ENCYCLOPEDIA OF MEDICINE

Isaac R. Berniker

Light sensitivity see Photosensitivity
Light therapy see Phototherapy
Light treatment see Ultraviolet light
treatment

KEY TERMS
Amylase—A digestive enzyme that breaks down
starch.
Lipid—A greasy organic compound that cannot be
dissolved in water. Triglycerides, which are broken
down by lipase, are one type of blood lipid.
Pancreas—An elongated gland situated across the
back of the abdomen behind the stomach. It
secretes both digestive enzymes and hormones.
Pancreatic hormones regulate the level of sugar in
the blood.
Pancreatitis—Inflammation of the pancreas, frequently caused by gallstones, alcohol abuse, viral
infection, or injury.
Turbidimetry—A technique of measurement that
analyzes the amount of sediment in a liquid.

Lipase test
Definition
The lipase test is a blood test performed to determine the serum level of a specific protein (enzyme)
involved in digestion. Lipase is an enzyme produced
by the pancreas, which is a large gland situated near
the stomach. Lipase works to break down a certain
type of blood lipid (triglycerides) into fatty acids.

peaks later and remains elevated longer, its determination is more useful in late diagnosis of acute pancreatitis. Conversely, however, lipase levels are not as
useful in diagnosing chronic pancreatic disease.

Lipase appears in the blood together with another
enzyme called amylase following damage to or diseases affecting the pancreas. It was once thought that
abnormally high lipase levels were associated only
with diseases of the pancreas. Other conditions are
now known to be associated with high lipase levels,
especially kidney failure and intestinal obstruction.
Diseases involving the pancreas, however, produce
much higher lipase levels than diseases of other
organs. Lipase levels in pancreatic disorders are often
5-10 times higher than normal.

Patients should be asked whether they are taking certain prescription drugs that can affect the
accuracy of the lipase test. Drugs that can cause elevated lipase levels include bethanechol, cholinergics,
codeine, indomethacin, meperidine, methacholine,
and morphine. Drugs that may decrease levels include
calcium ions.

Purpose
The lipase test is most often used in evaluating
inflammation of the pancreas (pancreatitis), but it is
also useful in diagnosing kidney failure, intestinal
obstruction, mumps, and peptic ulcers. Doctors often
order amylase and lipase tests at the same time to
help distinguish pancreatitis from ulcers and other
disorders in the abdomen. If the patient has acute
(sudden onset) pancreatitis, the lipase level usually
rises somewhat later than the amylase level–about
24-48 hours after onset of symptoms–and remains
abnormally high for 5-7 days. Because the lipase level
GALE ENCYCLOPEDIA OF MEDICINE

Precautions

Description
A lipase test is performed on a sample of the
patient’s blood, withdrawn from a vein into a vacuum
tube. The procedure, which is called a venipuncture,
takes about five minutes.

Preparation
The patient should have nothing to eat or drink
for 12 hours before the lipase test.

Risks
Risks for this test are minimal, but may include
slight bleeding from the puncture site, a small bruise or
swelling in the area, fainting, or feeling lightheaded.
2221

Lipase test

Luce, John M., ‘‘Approach to the Patient In a Critical
Care Setting.’’ In Textbook of Medicine, edited by
Lee Goldman and J. Claude Bennett, 21st ed. Vol. 1.
Philadelphia: W.B. Saunders Company, 2000,
pp. 483-4.
Tintinalli, Judith E., et al, editors. Emergency Medicine:
a comprehensive study guide. New York: McGraw-Hill,
2000.

Lipidoses

Normal results
Reference values for lipase determination are
laboratory- and method-specific. In general, normal
results are usually less than 200 units/L (triolein
methods by titration or turbidimetry).

Abnormal results
Increased lipase levels are found in acute pancreatitis, chronic relapsing pancreatitis, and pancreatic
cancer. High lipase levels also occur in certain liver
diseases, kidney failure, bowel obstruction, peptic
ulcer disease, and tumors or inflammation of the
salivary glands.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

to children, the parents often do not have the disorders themselves.
The symptoms, available treatments, and longterm consequences of these conditions vary greatly.
Some of the conditions become apparent shortly
after the infant is born; in others, symptoms may not
develop until adulthood. For most of the lipidoses,
diagnosis is suspected based on the symptoms and
family history. Blood tests, urine tests, and tissue
tests can be used to confirm the diagnosis. Genetic
testing can be used, in some cases, to identify the
defective gene. Some of these disorders can be
controlled with changes in the diet, medications, or
enzyme supplements. For many, no treatment is
available. Some may cause death in childhood or
contribute to a shortened life expectancy. Some of
the most common or most serious lipidoses are
discussed below.

Fabry’s disease
Causes and symptoms

Lipidoses
Definition
Lipidoses are heredity disorders, passed from
parents to their children, characterized by defects of
the digestive system that impair the way the body uses
fat from the diet. When the body is unable to properly
digest fats, lipids accumulate in body tissues in abnormal amounts.

Description
The digestion, storage, and use of fats from
foods is a complex process that involves hundreds
of chemical reactions in the body. In most people,
the body is already programmed by its genetic code
to produce all of the enzymes and chemicals necessary
to carry out these functions. These genetic instructions
are passed from parents to their offspring during
reproduction.
People with lipidoses are born without the
genetic codes needed to tell their bodies how to complete a particular part of the fat digestion process.
In most of these disorders, the body does not produce
a certain enzyme or chemical. Over 30 different
disorders of fat metabolism are related to genetic
defects. Although the defects are passed from parents
2222

Approximately 1 in every 40,000 males is born
with Fabry’s disease. This condition has an X-linked,
recessive pattern of inheritance, meaning that the
defective gene is carried on the X chromosome.
A female who carries a defective recessive gene on
one of her two X chromosomes has a 50% chance of
passing the defective gene to her sons who will develop
the disorder associated with the defective gene (a male
receives one X chromosome from his mother and one
Y chromosome from his father). She also has a 50%
chance of passing the defective recessive gene to her
daughters who will be carries of the disorder (like their
mother). Some female carries of Fabry’s disease show
mild signs of the disorder, especially cloudiness of the
cornea.
The gene that is defective in Fabry’s disease causes
a deficiency of the enzyme alpha-galactosidase A.
Without this enzyme, fatty compounds starts to line
the blood vessels. The collection of fatty deposits
eventually affects blood vessels in the skin, heart,
kidneys, and nervous system. The first symptoms in
childhood are pain and discomfort in the hands and
feet brought on by exercise, fever, stress, or changes
in the weather. A raised rash of dark red-purple spots
is common, especially on skin between the waistline
and the knees. Other symptoms include a decreased
ability to sweat and changes in the cornea or outer
layer of the eye. Although the disease begins in childhood, it progresses very slowly. Kidney and heart
problems develop in adulthood.
GALE ENCYCLOPEDIA OF MEDICINE

The diagnosis can be confirmed by a blood test
to measure for alpha-galactosidase A. Women who
are carries of the defective gene can also be identified
by a blood test.

Treatment
Treatment focuses on prevention of symptoms
and long-term complications. Daily doses of diphenylhydantoin (Dilantin) or carbamazapine (Tegretol) can
prevent or reduce the severity of pain in the hands and
feet associated with the condition. A low sodium, low
protein diet may be beneficial to those patients who
have some kidney complications. If kidney problems
progress, kidney dialysis or kidney transplantation may
be required. Enzyme replacement therapy is currently
being explored.

Prognosis
Although patients with Fabry’s disease usually
survive to adulthood, they are at increased risk for
stroke, heart attacks, and kidney damage.

Gaucher disease
Causes and symptoms
Gaucher (pronounced go-shay) disease is the most
common of the lipid storage disorders. It is found in
populations all over the world (20,00 to 40,000 people
have a type of the disease), and it occurs with equal
frequency in males and females. Gaucher disease has a
recessive pattern of inheritance, meaning that a person
must inherit a copy of the defective gene from both
parents in order to have the disease. The genetic defect
causes a deficiency of the enzyme glucocerebrosidase
that is responsible for breaking down a certain type of
fat and releasing it from fat cells. These fat cells begin
to crowd out healthy cells in the liver, spleen, bones,
and nervous system. Symptoms of Gaucher disease
can start in infancy, childhood, or adulthood.
Three types of Gaucher disease have been identified, but there are many variations in how symptoms
develop. Type 1 is the most common and affects both
children and adults. It occurs much more often in
people of Eastern European and Russian Jewish
(Ashkenazi) ancestry, affecting 1 out of every 450
live births. The first signs of the disease include an
enlarged liver and spleen, causing the abdomen to
swell. Children with this condition may be shorter
than normal. Other symptoms include tiredness,
pain, bone deterioration, broken bones, anemia, and
GALE ENCYCLOPEDIA OF MEDICINE

increased bruising. Type 2 Gaucher disease is more
serious, beginning within the first few months after
birth. Symptoms, which are similar to those in Type
1, progress rapidly, but also include nervous system
damage. Symptoms of Type 3 Gaucher disease begin
during early childhood with symptoms like Type 1.
Unlike Type 2, the progress of the disease is slower,
although it also includes nervous system damage.

Diagnosis
Gaucher disease may be suspected based on symptoms and is confirmed with a blood test for levels of
the enzyme. Samples of tissue from an affected area
may also be used to confirm a diagnosis of the disease.

Treatment
The symptoms of Gaucher disease can be stopped
and even reversed by treatment with injections of
enzyme replacements. Two enzyme drugs currently
available are alglucerase (Ceredase) and imiglucerase
(Cerezyme). Other treatments address specific symptoms such as anemia, broken bones, or pain.

Prognosis
The pain and deformities associated with symptoms
can make coping with this illness very challenging for
individuals and families. With treatment and control of
symptoms, people with Type 1 Gaucher disease may
lead fairly long and normal lives. Most infants with
Type 2 die before the age of 2. Children with Type 3
Gaucher disease may survive to adolescence and early
adulthood.

Krabbe’s disease
Causes and symptoms
Krabbe’s disease is caused by a deficiency of the
enzyme galactoside beta-galactosidase. It has a recessive pattern of inheritance and is believed to occur in 1
of 40,000 births in the United States. This condition,
which is also called globoid cell leukodystrophy or
Krabbe leukodystrophy, is characterized by acute
nervous system degeneration. It develops in early
infancy with initial symptoms of irritability, vomiting
and episodes of partial unconsciousness. Symptoms
progress rapidly to seizures, difficulty swallowing,
blindness, deafness, mental retardation, and paralysis.

Treatment
No treatment is available.
2223

Lipidoses

Diagnosis

Lipidoses

Prognosis

Refsum’s disease

Children born with Krabbe’s disease die in infancy.

Causes and symptoms

Niemann-pick disease
Causes and symptoms
At least five different forms of Niemann-Pick
disease (NPD) have been identified. The different types
seem to be related to the activity level of the enzyme
sphingomyelinase. In patients with Types A and B NPD,
there is a build up of sphingomyelin in cells of the brain,
liver, spleen, kidney and lung. Type A is the most common form of NPD and the most serious, with death
usually occurring by the age of 18 months. Symptoms
develop within the first few months of life and include
poor appetite, failure to grow, enlarged liver and spleen,
and the appearance of cherry red spots in the retina of
the eye. Type B develops in infancy or childhood with
symptoms of mild liver or spleen enlargement and lung
problems. Some adults with this form (Type E) may also
show a loss of muscle coordination. Types C or D NPD
are related to cholesterol transfer out of cells. Children
with Types C or D grow normally in early childhood, but
eventually develop difficulty in walking and loss of muscle coordination. Ultimately, the nervous system
becomes severely damaged and these patients die. Type
C occurs in any population, while Type D has been
identified only in patients from Nova Scotia, Canada.

Diagnosis
Diagnosis is confirmed by analyzing a sample of
tissue. Prenatal diagnosis of Types A and B of NPD can
be done with amniocentesis or chorionic villus sampling.

Treatment
Treatment consists of supportive care to deal with
symptoms and the development of complications.
Bone marrow transplantation is being investigated as
a possible treatment. Low-cholesterol diets may be
helpful for patients with Types C and D.

Prognosis
Patients with Type A NPD usually die within the
first year and a half of life. Type B patients generally
live to adulthood but suffer from significant liver and
lung problems. With Types C and D NPD, there is
significant nervous system damage leading to severe
muscle spasms, seizures, and eventually, to coma and
death. Some patients with Types C and D die in childhood, while less severely affected patients may survive
to adulthood.
2224

Refsum’s disease has a recessive pattern of inheritance and affects populations from Northern Europe,
particularly Scandinavians most frequently. It is due to a
deficiency of phytanic acid hydroxylase, an enzyme that
breaks down a fatty acid called phytanic acid. This condition affects the nervous system, eyes, bones, and skin.
Symptoms, which usually appear by age 20, include
vision problems [retinitis pigmentosa and rhythmic
eye movements (nystagmus)], loss of muscle coordination, loss of sense of smell (anosmia), pain, numbness,
and elevated protein in the cerebrospinal fluid.

Treatment
A diet free of phytanic acid (found in dairy products,
tuna, cod, haddock, lamb, stewed beef, white bread,
white rice, boiled potatoes, and egg yolk) can reduce
some of the symptoms. Plasmapheresis, a process
where whole blood is removed from the body, processed
through a filtering system, and then return to the body,
may be used to filter phytanic acid from the blood.

Tay-sachs disease
Causes and symptoms
Tay-Sachs disease (TSD) is a fatal condition caused
by a deficiency of the enzyme hexosaminidase A
(Hex-A). The defective gene that causes this disorder
is found in roughly 1 in 250 people in the general
population. However, certain populations have significantly higher rates of TSD. French-Canadians living
near the St. Lawrence River and in the Cajun regions of
Louisiana are at higher risk of having a child with TSD.
The highest risk seems to be in people of Eastern
European and Russian Jewish (Ashkenazi) descent.
Tay-Sachs disease has a recessive pattern of inheritance,
and approximately 1 in every 27 people of Jewish
ancestry in the United States carries the TSD gene.
Symptoms develop in infancy and are due to the accumulation of a fatty acid compound in the nervous
system. Early symptoms include loss of vision and physical coordination, seizures, and mental retardation.
Eventually, the child develops problems with breathing
and swallowing. Blindness, paralysis, and death follow.

Diagnosis
Carriers of the Tay-Sachs related gene can be
identified with a blood test. Amniocentesis or chorionic
villi sampling can be used to determine if the fetus has
Tay-Sachs disease.
GALE ENCYCLOPEDIA OF MEDICINE

There is no treatment for Tay-Sachs disease.
Parents who are identified as carriers may want to
seek genetic counseling. If a fetus is identified as
having TSD, parents may consider termination of
the pregnancy.

Prognosis
Children born with Tay-Sachs disease become
increasingly debilitated; most die by about age four.

Wolman’s disease
Causes and symptoms
Wolman’s disease is caused by a genetic defect
(with a recessive pattern of inheritance) that results
in deficiency of an enzyme that breaks down cholesterol. This causes large amounts of fat to accumulate
in body tissues. Symptoms begin in the first few weeks
of life and include an enlarged liver and spleen, adrenal
calcification (hardening of adrenal tissue due to deposits of calcium salts), and fatty stools.

KEY TERMS
Amniocentesis—A procedure where a needle is
inserted through the abdomen into the uterus of a
pregnant woman to remove a small amount of the
fluid that surrounds the developing fetus. This test
can be preformed at about week 16 of the pregnancy. Cells from the fetus can be tested for genetic
defects.
Chorionic villi sampling—A procedure to remove a
small tissue sample of the placenta, the sac that
surrounds the developing fetus. This test can be
performed as early as week 10 of the pregnancy.
The tissue can be tested for genetic defects.
Lipids—Organic compounds not soluble in water,
but soluble in fat solvents such as alcohol. Lipids
are stored in the body as energy reserves and are
also important components of cell membranes.
Recessive—Refers to an inherited characteristic or
trait that is expressed only when two copies of the
gene responsible for it are present.
X-linked—Refers to a gene carried on the X chromosome, one of the two sex chromosomes.

Treatment
No treatment is currently available.

Prognosis
Death generally occurs before six months of age.

National Tay-Sachs and Allied Diseases Association. 2001
Beacon St., Suite 204, Brookline, MA 02146. (800) 9068723. <http://www.ntsad.org>.
OTHER

Prevention
Couples who have family histories of genetic
defects can undergo genetic testing and counseling to
see if they are at risk for having a child with one of the
lipidoses disorders. During pregnancy, cell samples
can be collected from the fetus using amniocentesis
or chorionic villi sampling. The results of these test
can indicate if the developing fetus has a lipidosis
disorder. Termination of the pregnancy may be considered in some cases.
Resources
ORGANIZATIONS

National Institute of Neurological Disorders and Stroke.
P.O. Box 5801, Bethesda, MD 20824. (800) 352-9424.
<http://www.ninds.nih.gov/index.htm>.
National Niemann-Pick Foundation. 3734 E. Olive Ave.,
Gilbert, AZ 85234. (602) 497-6638.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Gaucher Disease Treatment Program. <http://
gaucher.mgh.harvard.edu>.
Rare Genetic Diseases In Children: An Internet Resource
Gateway. <http://mcrcr2.med.nyu.edu/murphp01/
homenew.htm>.

Altha Roberts Edgren

Lipoproteins test
Definition
Lipoproteins are the ‘‘packages’’ in which cholesterol and triglycerides travel throughout the body.
Measuring the amount of cholesterol carried by each
type of lipoprotein helps determine a person’s risk for
cardiovascular disease (disease that affects the heart
and blood vessels, also called CVD).
2225

Lipoproteins test

Treatment

Lipoproteins test

Purpose
Cholesterol and triglycerides are fat-like substances
called lipids. Cholesterol is used to build cell membranes
and hormones. The body makes cholesterol and gets
it from food. Triglycerides provide a major source of
energy to the body tissues. Both cholesterol and triglycerides are vital to body function, but an excess of either
one, especially cholesterol, puts a person at risk of
cardiovascular disease.
Because cholesterol and triglycerides can’t dissolve
in watery liquid, they must be transported by something
that can dissolve in blood serum. Lipoproteins contain
cholesterol and triglycerides at the core and an outer
layer of protein, called apolipoprotein.
There are four major classes of lipoproteins:
chylomicrons, very low-density lipoproteins (VLDL),
low-density lipoproteins (LDL), and high-density
lipoproteins (HDL). There also are less commonly
measured classes such as lipoprotein(a) and subtypes
of the main classes. Each lipoprotein has characteristics that make the cholesterol it carries a greater or
lesser risk. Measuring each type of lipoprotein helps
determine a person’s risk for cardiovascular disease
more accurately than cholesterol measurement alone.
When a person is discovered to be at risk, treatment by
diet or medication can be started and his or her
response to treatment monitored by repeated testing.

Description

Low-density lipoproteins (LDL)
LDL, often called ‘‘bad’’ cholesterol, is formed
primarily by the breakdown of VLDL. LDL contains
little triglycerides and a large amount of cholesterol
(60-70% of a person’s total cholesterol). Although the
particles are much smaller than chylomicrons and
VLDL, LDL particles can vary in size and chemical
structure. These variations represent subclasses within
the LDL class. Serum from a person with a large
amount of LDL will be clear.
LDL carries cholesterol in the blood and deposits it
in body tissues and in the walls of blood vessels, a condition known as atherosclerosis. The amount of LDL in
a person’s blood is directly related to his or her risk of
cardiovascular disease. The higher the LDL level, the
greater the risk. LDL is the lipoprotein class most used
to trigger and monitor cholesterol lowering therapy.
High-density lipoproteins (HDL)
HDL is often called ‘‘good’’ cholesterol. HDL
removes excess cholesterol from tissues and vessel
walls and carries it to the liver, where it is removed
from the blood and discarded. The amount of HDL in
a person’s blood is inversely related to his or her risk
of cardiovascular disease. The lower the HDL level,
the greater the risk; the higher the level, the lower the
risk. The smallest lipoprotein, it contains 20-30% of
a person’s total cholesterol and can be separated into
two major subclasses.

Chylomicrons
Chylomicrons are made in the intestines from
the triglycerides in food. They contain very little cholesterol. Chylomicrons circulate in the blood, getting
smaller as they deposit the triglycerides in fatty tissue.
Twelve hours after a meal, they are gone from circulation. Serum collected from a person directly after
eating will form a creamy layer on the top if left
undisturbed and refrigerated overnight. This creamy
layer is the chylomicrons.
Very low-density lipoproteins (VLDL)
VLDL are formed in the liver by the combination
of cholesterol, triglycerides formed from circulating
fatty acids, and apolipoprotein. This lipoprotein
particle is smaller than a chylomicron, and contains
less triglyceride but more cholesterol (10-15% of a
person’s total cholesterol). As the VLDL circulates in
the blood, triglycerides are deposited and the particle
gets smaller, eventually becoming a low-density lipoprotein (LDL). Serum from a person with a large
amount of VLDL will be cloudy.
2226

Lipoprotein(a)
Lipoprotein(a) is found in lower concentrations
than other lipoproteins, yet it carries a unique and
significant risk for cardiovascular disease. Because
of its similarity to LDL, test methods often don’t
measure it separately, but include it within the LDL
class. Testing specifically for this class may uncover
why a person is not responding to standard cholesterol-lowering treatment. High lipoprotein(a) levels
may not respond to treatment aimed at high LDL.
Measurement guidelines
The Expert Panel of the National Cholesterol
Education Program (NCEP) sponsored by the
National Institutes of Health has published guidelines for the detection of high cholesterol in adults.
The NCEP panel recommends that adults over the age
of 20 be tested for cholesterol and HDL every five
years. If the cholesterol is high, the HDL is low (below
35 mg/dl), or other risk factors are present, a complete
GALE ENCYCLOPEDIA OF MEDICINE

Measurement methods
There are a variety of methods to measure the
lipoprotein classes. All require separation of the classes
before they can be measured. One way to separate them
is by spinning serum (the yellow, watery liquid that
separates from the cells when blood clots) for a long
time in a high-speed centrifuge (called ultracentrifugation). The most dense classes will settle toward the
bottom, the least dense toward the top. Following centrifugation, the most complete measurement of all the
lipoprotein classes is done using electrophoresis. This
procedure measures the quantity of each lipoprotein
class based on its movement in an electrical field.
In 2003, a new test called the vertical auto profile
or VAP, was developed that provides detailed measurements of cholesterol subclasses. These subclasses
play important roles in patients later developing heart
disease. The new tests were predicted to help identify
important, emerging risk factors for heart disease.
Other, less extensive procedures also are used.
For example, if only HDL is to be measured, a chemical is added to the serum that will clump the other
classes, leaving HDL free in the serum to be measured
by a chemical method. LDL often is not measured
directly but its level is calculated based on the measurements of total cholesterol, HDL, and triglycerides.
The formula is called the Friedewald formula:
LDL = total cholesterol - HDL - (triglycerides/5).
The calculated result will be inaccurate in a person
with high triglycerides. Results usually are available
the same or following day.

Preparation
The patient must fast for 12 hours before the test,
eating nothing and drinking only water. The person
should not have alcohol for 24 hours before the test.
There should be a stable diet and no illnesses occurring
in the preceding two weeks.
A lipoproteins test requires 5 mL (milliliters) of
blood. A person’s physical position while having blood
collected affects the results. Values from blood drawn
while a person is sitting may be different from those
while the person is standing. If repeated testing is done,
the person should be in the same position each time.

KEY TERMS
Atherosclerosis—Disease of blood vessels caused
by deposits of cholesterol on the inside walls of the
vessels.
Cardiovascular disease—Disease that affects the
heart and blood vessels.
Cholesterol—A fat-like substance called a lipid. It
is used to build cell membranes and hormones. The
body makes cholesterol and gets it from food.
Lipoproteins—The packages in which cholesterol
and triglycerides travel throughout the body.

the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve
discomfort.

Normal results
People with HDL levels between 45 mg/dl and
59 mg/dl carry an average risk for cardiovascular
disease. People with HDL levels above 60 mg/dl
have a negative risk factor and appear to be protected
from cardiovascular disease.
LDL levels below 130 mg/dl are desirable.
Some people have normal variations in their lipoprotein and total cholesterol levels. Repeat testing
may be necessary, especially if a value is at a borderline
risk category point.

Abnormal results
People with HDL levels 36-44 mg/dl have a moderate risk of cardiovascular disease. HDL levels below
35 mg/dl are a major risk.
LDL levels 130-159 mg/dl place a person at a
borderline high risk of cardiovascular disease; levels
above 160 mg/dl place a person at high risk. Relative
proportions between HDL and LDL are important
also. Results of a large clinical trial in 2003 showed
that the new VAP cholesterol tests increased lipidlowering therapy by 59% in high-risk patients with
diabetes.
Resources
PERIODICALS

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Doctors Laboratory to Offer VAP Expanded Cholesterol
Test.’’ Heart Diseases Weekly September 7, 2003: 35.
‘‘Results of a Prospective, Multi-center Study Showed that
the Availability of Lipoprotein Subclass Testing
2227

Lipoproteins test

lipoprotein profile that includes total cholesterol, triglycerides, HDL, and calculated LDL should be done.

Liposuction

(Vertical Auto profile û VAP û Cholesterol Test)
Increased Use of Lipid-lowering Therapy by 59% in
High-risk Patients with Type 2 Diabetes.’’ Diagnostics &
Imaging Week June 19, 2003: 6.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Nancy J. Nordenson
Teresa G. Odle

Liposuction
Definition
Liposuction, also known as lipoplasty or suctionassisted lipectomy, is cosmetic surgery performed to
remove unwanted deposits of fat from under the
skin. The doctor sculpts and recontours the patient’s
body by removing excess fat deposits that have been
resistant to reduction by diet or exercise. The fat is
permanently removed from under the skin with a
suction device.

Purpose
Liposuction is intended to reduce and smooth the
contours of the body and improve the patient’s
appearance. Its goal is cosmetic improvement. It is
the most commonly performed cosmetic procedure in
the United States.
Liposuction does not remove large quantities of
fat and is not intended as a weight reduction technique. The average amount of fat removed is about a
liter, or a quart. Although liposuction is not intended
to remove cellulite (lumpy fat), some doctors believe
that it improves the appearance of cellulite areas
(thighs, hips, buttocks, abdomen, and chin).
A new technique called liposhaving shows more
promise at reducing cellulite.

Precautions
Liposuction is most successful on patients who
have firm, elastic skin and concentrated pockets of
fat in cellultite areas. To get good results after fat
removal, the skin must contract to conform to the
2228

‘‘Before’’ photo of patient undergoing liposuction.
(Photograph by I. Richard Toranto, M.D., Custom Medical Stock
Photo. Reproduced by permission.)

new contours without sagging. Older patients have
less elastic skin and therefore may not be good candidates for this procedure. Patients with generalized fat
distribution, rather than localized pockets, are not
good candidates.
Patients should be in good general health and free
of heart or lung disease. Patients with poor circulation
or who have had recent surgery at the intended site of
fat reduction are not good candidates.

Description
Most liposuction procedures are performed under
local anesthesia (loss of sensation without loss of consciousness) by the tumescent or wet technique. In this
technique, large volumes of very dilute local anesthetic
(a substance that produces anesthesia) are injected
under the patient’s skin, making the tissue swollen
and firm. Epinephrine is added to the solution to
GALE ENCYCLOPEDIA OF MEDICINE

The cost of liposuction can vary depending upon
the standardized fees in the region of the country
where it is performed, the extent of the area being
treated, and the person performing the procedure.
Generally, small areas, such as the chin or knees, can
be done for as little as $500, while more extensive
treatment, such as when hips, thighs, and abdomen
are done simultaneously, can cost as much as $10,000.
These procedures are cosmetic and are not covered by
most insurance policies.

Preparation
The doctor will do a physical exam and may order
blood work to determine clotting time and hemoglobin level for transfusions should the need arise. The
patient may be placed on antibiotics immediately prior
to surgery to ward off infection.

Aftercare

‘‘After’’ photo of same patient following liposuction.
(Photograph by I. Richard Toranto, M.D., Custom Medical Stock
Photo. Reproduced by permission.)

reduce bleeding, and make possible the removal of
larger amounts of fat.
The doctor first numbs the skin with an injection
of local anesthetic. After the skin is desensitized, the
doctor makes a series of tiny incisions, usually 0.120.25 in (3-6 mm) in length. The area is then flooded
with a larger amount of local anesthetic. Fat is then
extracted with suction through a long, blunt hollow
tube called a cannula. The doctor repeatedly pushes
the cannula through the fat layers in a radiating pattern creating tunnels, removing fat, and recontouring
the area. Large quantities of intravenous fluid (IV) is
given during the procedure to replace lost body fluid.
Blood transfusions are possible.
Some newer modifications to the procedure
involve the use of a cutting cannula called a liposhaver,
or the use of ultrasound to help break up the fat
deposits. The patient is awake and comfortable during
these procedures.
GALE ENCYCLOPEDIA OF MEDICINE

After the surgery, the patient will need to wear a
support garment continuously for 2-3 weeks. If ankles
or calves were treated, support hose will need to be
worn for up to 6 weeks. The support garments can
be removed during bathing 24 hours after surgery.
A drainage tube, under the skin in the area of the
procedure, may be inserted to prevent fluid build-up.
Mild side effects can include a burning sensation at
the site of the surgery for up to one month. The patient
should be prepared for swelling of the tissues below the
operated site for 6-8 weeks after surgery. Wearing the
special elastic garments will help reduce this swelling
and help to achieve the desired final results.
The incisions involved in this procedure are tiny,
but the surgeon may close them with stitches or
staples. These will be removed the day after surgery.
However, three out of eight doctors use no sutures.
Minor bleeding or seepage through the incision site
is common after this procedure. Wearing the elastic
bandage or support garment helps reduce fluid loss.
This operation is virtually painless. However, for
the first postoperative day, there may be some discomfort which will require light pain medication. Soreness
or aching may persist for several days. The patient can
usually return to normal activity within a week.
2229

Liposuction

The length of time required to perform the procedure varies with the amount of fat that is to be
removed and the number of areas to be treated.
Most operations take from 30 minutes to 2 hours,
but extensive procedures can take longer. The length
of time required also varies with the manner in which
the anesthetic is injected.

Liposuction

Thigh

Buttocks

Abdomen

Common entry sites for liposuction procedures. (Illustration by Electronic Illustrators Group.)

Postoperative bruising will go away by itself within 1014 days. Postoperative swelling begins to go down
after a week. It may take 3-6 months for the final
contour to be reached.

Risks
Liposuction under local anesthesia using the
tumescent technique is exceptionally safe. A 1995
study of 15,336 patients showed no serious complications or deaths. Another study showed a 1% risk
factor. However, as with any surgery, there are some
risks and serious complications. Death is possible.
The main hazards associated with this surgery
involve migration of a blood clot or fat globule to the
heart, brain, or lungs. Such an event can cause a heart
attack, stroke, or serious lung damage. However, this
complication is rare and did not occur even once in the
study of 15,336 patients. The risk of blood clot formation is reduced with the wearing of special girdle-like
compression garments after the surgery, and with the
resumption of normal mild activity soon after surgery.
Staying in bed increases the risk of clot formation,
but not getting enough rest can result in increased
swelling of the surgical area. Such swelling is a result
of excess fluid and blood accumulation, and generally
comes from not wearing the compression garments.
If necessary, this excess fluid can be drained off with
a needle in the doctor’s office.
Infection is another complication, but this rarely
occurs. If the physician is skilled and works in a sterile
environment, infection should not be a concern.
2230

If too much fat is removed, the skin may peel in
that area. Smokers are at increased risk for shedding
skin because their circulation is impaired. Another
and more serious hazard of removing too much fat is
that the patient may go into shock. Fat tissue has an
abundant blood supply and removing too much of it at
once can cause shock if the fluid is not replaced.
A rare complication is perforation or puncture of
an organ. The procedure involves pushing a cannula
vigorously through the fat layer. If the doctor pushes
too hard or if the tissue gives way too easily under the
force, the blunt hollow tube can go too far and injure
internal organs.
Liposuction can damage superficial nerves. Some
patients lose sensation in the area that has been suctioned, but feeling usually returns with time.

Normal results
The loss of fat cells is permanent, and the patient
should have smoother, more pleasing body contours
without excessive bulges. However, if the patient overeats, the remaining fat cells will grow in size. Although
the patient may gain weight back, the body should
retain the new proportions and the suctioned area
should remain proportionally smaller.
Tiny scars about 0.25-0.5 in (6-12 mm) long at the
site of incision are normal. The doctor usually makes the
incisions in places where the scars are not likely to show.
In some instances, the skin may appear rippled,
wavy, or baggy after surgery. Pigmentation spots may
GALE ENCYCLOPEDIA OF MEDICINE

Cellulite—Cellulite is dimply skin caused by
uneven fat deposits beneath the surface.
Epinephrine—Epinephrine is a drug that causes
blood vessels to constrict or narrow. It is used in
local anesthetics to reduce bleeding.
Hemoglobin—Hemoglobin is the component of
blood that carries oxygen to the tissues.
Liposhaving—Liposhaving involves removing fat
that lies closer to the skins surface by using a
needle-like instrument that contains a sharp-edged
shaving device.
Tumescent technique—The tumescent technique
of liposuction involves swelling, or tumescing, the
tissue with large volumes of dilute anesthetic.

develop. The recontoured area may be uneven. This
unevenness is common, occurring in 5-20% of the
cases, and can be corrected with a second procedure
that is less extensive than the first.
Resources
PERIODICALS

Taylor, Mia, Lloyd A. Hoffman, and Michael Lieberman.
‘‘Intestinal Perforation after Suction Lipoplasty:
A Case Report and Review of the Literature.’’
Annals of Plastic Surgery 38, no. 2: 169-172.
ORGANIZATIONS

American Society of Aesthetic Plastic Surgery. (888)
272-7711.
American Society of Plastic and Reconstructive Surgeons.
44 E. Algonquin Rd., Arlington Heights, IL 60005.
(847) 228-9900. <http://www.plasticsurgery.org>.
Lipoplasty Society of North America. (800) 848-1991.

Louann W. Murray, PhD

Listeria monocytogenes infection see
Listeriosis

Listeriosis
Definition
Listeriosis is an illness caused by the bacterium
Listeria monocytogenes that is acquired by eating
contaminated food. The organism can spread to the
GALE ENCYCLOPEDIA OF MEDICINE

blood stream and central nervous system. During pregnancy, listeriosis often causes miscarriage or stillbirth.

Description
Listeriosis is caused by an infection with the
bacterium Listeria monocytogenes. This bacteria can
be carried by many animals and birds, and it has
been found in soil, water, sewage, and animal feed.
Five out of every 100 people carry Listeria monocytogenes in their intestines. Listeriosis is considered a
‘‘food-borne illness’’ because most people are probably infected after eating food contaminated with
Listeria monocytogenes. However, a woman can
pass the bacteria to her baby during pregnancy. In
addition, there have been a few cases where workers
have developed Listeria skin infections by touching
infected calves or poultry.
In the 1980s, the United States government began
taking measures to decrease the occurrence of listeriosis. Processed meats and dairy products are now
tested for the presence of Listeria monocytogenes.
The Food and Drug Administration (FDA) and the
Food Safety and Inspection Service (FSIS) can legally
prevent food from being shipped, or order food
recalls, if they detect any Listeria bacteria. These
inspections, in combination with the public education
regarding the proper handling of uncooked foods,
appear to be working. In 1989, there were 1,965 cases
of listeriosis with 481 deaths. In 1993, the numbers fell
to 1,092 cases with 248 deaths.
In 1996, the Centers for Disease Control and
Prevention (CDC) began a nationwide food-borne
disease surveillance program called ‘‘FoodNet,’’ in
which seven states were participating by January
1997. Results from the program indicated that, in
1996, one person out of every 200,000 people got
listeriosis. FoodNet also revealed that the hospitalization rate was higher for listeriosis (94%) than for
any other food-borne illness. In addition, FoodNet
found that the Listeria bacteria reached the blood
and cerebrospinal fluid in 89% of cases, a higher
percentage than in any other food-borne illness.
Persons at particular risk for listeriosis include
the elderly, pregnant women, newborns, and those
with a weakened immune system (called ‘‘immunocompromised’’). Risk is increased when a person
suffers from diseases such as AIDS, cancer, kidney
disease, diabetes mellitus, or by the use of certain medications. Infection is most common in babies younger
than one month old and adults over 60 years of age.
Pregnant women account for 27% of the cases and
immunocompromised persons account for almost
2231

Listeriosis

KEY TERMS

Listeriosis

70%. Persons with AIDS are 280 times more likely to
get listeriosis than others.

Causes and symptoms
As noted, persons become infected with Listeria
monocytogenes by eating contaminated food. Listeria
has been found on raw vegetables, fish, poultry, raw
(unpasteurized) milk, fresh meat, processed meat
(such as deli meat, hot dogs, and canned meat), and
certain soft cheeses. Listeriosis outbreaks in the
United States since the 1980s have been linked to cole
slaw, milk, Mexican-style cheese, undercooked hot dogs,
undercooked chicken, and delicatessen foods. Unlike
most other bacteria, Listeria monocytogenes does not
stop growing when food is in the refrigerator – its growth
is merely slowed. Fortunately, typical cooking temperatures and the pasteurization process do kill this bacteria.
Listeria bacteria can pass through the wall of the
intestines, and from there they can get into the blood
stream. Once in the blood stream, they can be transported anywhere in the body, but are commonly found
the central nervous system (brain and spinal cord);
and in pregnant women they are often found in the
placenta (the organ which connects the baby’s umbilical cord to the uterus). Listeria monocytogenes live
inside specific white blood cells called macrophages.
Inside macrophages, the bacteria can hide from
immune responses and become inaccessible to certain
antibiotics. Listeria bacteria are capable of multiplying
within macrophages, and then may spread to other
macrophages.
After consuming food contaminated with this
bacteria, symptoms of infection may appear anywhere
from 11-70 days later. Most people do not get any
noticeable symptoms. Scientists are unsure, but they
believe that Listeria monocytogenes can cause upset
stomach and intestinal problems just like other foodborne illnesses. Persons with listeriosis may develop
flu-like symptoms such as fever, headache, nausea and
vomiting, tiredness, and diarrhea.
Pregnant women experience a mild, flu-like illness
with fever, muscle aches, upset stomach, and intestinal
problems. They recover, but the infection can cause
miscarriage, premature labor, early rupture of the birth
sac, and stillbirth. Unfortunately, half of the newborns
infected with Listeria will die from the illness.
There are two types of listeriosis in the newborn
baby: early-onset disease and late-onset disease.
Early-onset disease refers to a serious illness that is
present at birth and usually causes the baby to be
born prematurely. Babies infected during the
2232

pregnancy usually have a blood infection (sepsis) and
may have a serious, whole body infection called granulomatosis infantisepticum. When a full-term baby
becomes infected with Listeria during childbirth, that
situation is called late-onset disease. Commonly, symptoms of late-onset listeriosis appear about two weeks
after birth. Babies with late-term disease typically have
meningitis (inflammation of the brain and spinal tissues); yet they have a better chance of surviving than
those with early-onset disease.
Immunocompromised adults are at risk for a
serious infection of the blood stream and central
nervous system (brain and spinal cord). Meningitis
occurs in about half of the cases of adult listeriosis.
Symptoms of listerial meningitis occur about four
days after the flu-like symptoms and include fever,
personality change, uncoordinated muscle movement,
tremors, muscle contractions, seizures, and slipping in
and out of consciousness.
Listeria monocytogenes causes endocarditis in
about 7.5% of the cases. Endocarditis is an inflammation of heart tissue due to the bacterial infection.
Listerial endocarditis causes death in about half of
the patients. Other diseases which have been caused
by Listeria monocytogenes include brain abscess,
eye infection, hepatitis (liver disease), peritonitis
(abdominal infection), lung infection, joint infection, arthritis, heart disease, bone infection, and
gallbladder infection.

Diagnosis
Listeriosis may be diagnosed and treated by infectious disease specialists and internal medicine specialists. The diagnosis and treatment of this infection
should be covered by most insurance providers.
The only way to diagnose listeriosis is to isolate
Listeria monocytogenes from blood, cerebrospinal
fluid, or stool. A sample of cerebrospinal fluid is
removed from the spinal cord using a needle and
syringe. This procedure is commonly called a spinal
tap. The amniotic fluid (the fluid which bathes the
unborn baby) may be tested in pregnant women
with listeriosis. This sample is obtained by inserting a
needle through the abdomen into the uterus and withdrawing fluid. Listeria grows well in laboratory media
and test results can be available within a few days.

Treatment
Listeriosis is treated with the antibiotics ampicillin
(Omnipen) or sulfamethoxazole-trimethoprim (Bactrim,
Septra). Because the bacteria live within macrophage
GALE ENCYCLOPEDIA OF MEDICINE

Abscess—An accumulation of pus caused by
localized infection in tissues or organs. Listeria
monocytogenes can cause abscesses in many
organs including the brain, spleen, and liver.
Immunocompromised—To have a poor immune
system due to disease or medication. Immunocompromised persons are at risk for developing infections
because they can’t fight off microorganisms like
healthy persons can.
Macrophages—White blood cells whose job is to
destroy invading microorganisms. Listeria monocytogenes avoids being killed and can multiply within
the macrophage.
Meningitis—An inflammation of the tissues that
surround the brain and spinal cord. It can be caused
by a bacterial infection.
Sepsis—The presence of bacteria in the blood
stream, a normally sterile environment.

cheese, feta, Brie, Camembert, and blue cheese
(cottage cheese is safe), thoroughly cook leftovers
and ready-to-eat foods (such as hot-dogs), and
avoid foods from the deli.
For all people, the risk of listeriosis can be reduced
by taking these precautions:


Completely cook all meats and eggs.



Carefully wash raw vegetables before eating.



Keep raw meat away from raw vegetables and
prepared foods. After cutting raw meat, wash the
cutting board with detergent before using it for
vegetables.



Avoid drinking unpasteurized milk or foods made
from such milk.



Wash hands thoroughly after handling raw meat.



Follow the instructions on food labels. Observe food
expiration dates and storage conditions.

Resources
OTHER

cells, treatment may be difficult and the treatment periods may vary. Usually, pregnant women are treated for
two weeks; newborns, two to three weeks; adults with
mild disease, two to four weeks; persons with meningitis,
three weeks; persons with brain abscesses, six weeks; and
persons with endocarditis, four to six weeks.
Patients are often hospitalized for treatment and
monitoring. Other drugs may be provided to relieve
pain and fever and to treat other reactions to the
infection.

Prognosis
The overall death rate for listeriosis is 26%. This
high death rate is due to the serious illness suffered
by newborns, the elderly, and immunocompromised
persons. Healthy adults and older children have a
low death rate. Complications of Listeria infection
include: meningitis, sepsis, miscarriage, stillbirth,
pneumonia, shock, endocarditis, abscess (localized
infection) formation, and eye inflammation.

‘‘Preventing Foodborne Illness: Listeriosis.’’ Centers for
Disease Control. <http://www.cdc.gov/ncidad/diseases/
foodborn/lister.htm>.

Belinda Rowland, PhD

Lithotripsy
Definition
Lithotripsy is the use of high-energy shock waves
to fragment and disintegrate kidney stones. The shock
wave, created by using a high-voltage spark or an
electromagnetic impulse, is focused on the stone.
This shock wave shatters the stone and this allows
the fragments to pass through the urinary system.
Since the shock wave is generated outside the body,
the procedure is termed extracorporeal shock wave
lithotripsy, or ESWL.

Purpose
Prevention
The United States government has already done
much to prevent listeriosis. Persons at extremely
high risk (pregnant women, immunocompromised
persons, etc.) must use extra caution. High risk
persons should: avoid soft cheeses, such as Mexican
GALE ENCYCLOPEDIA OF MEDICINE

ESWL is used when a kidney stone is too large to
pass on its own, or when a stone becomes stuck in a
ureter (a tube which carries urine from the kidney to
the bladder) and will not pass. Kidney stones are
extremely painful and can cause serious medical
complications if not removed.
2233

Lithotripsy

KEY TERMS

Lithotripsy

Precautions
ESWL should not be considered for patients
with severe skeletal deformities, patients weighing
over 300 lbs (136 kg), patients with abdominal aortic
aneurysms, or patients with uncontrollable bleeding
disorders. Patients who are pregnant should not be
treated with ESWL. Patients with cardiac pacemakers
should be evaluated by a cardiologist familiar with
ESWL. The cardiologist should be present during the
ESWL procedure in the event the pacemaker needs to
be overridden.

Description
Lithotripsy uses the technique of focused shock
waves to fragment a stone in the kidney or the ureter.
The patient is placed in a tub of water or in contact
with a water-filled cushion, and a shock wave is
created which is focused on the stone. The wave
shatters and fragments the stone. The resulting debris,
called gravel, then passes through the remainder of the
ureter, through the bladder, and through the urethra
during urination. There is minimal chance of damage
to skin or internal organs because biologic tissues are
resilient, not brittle, and because the the shock waves
are not focused on them.

Preparation
Prior to the lithotripsy procedure, a complete
physical examination is done, followed by tests to
determine the number, location, and size of the
stone or stones. A test called an intravenous pyelogram, or IVP, is used to locate the stones. An IVP
involves injecting a dye into a vein in the arm. This
dye, which shows up on x ray, travels through the
bloodstream and is excreted by the kidneys. The dye
then flows down the ureters and into the bladder.
The dye surrounds the stones, and x rays are then
used to evaluate the stones and the anatomy of the
urinary system. (Some people are allergic to the dye
material, so it cannot be used. For these people,
focused sound waves, called ultrasound, can be
used to see where the stones are located.) Blood
tests are done to determine if any potential bleeding
problems exist. For women of childbearing age,
a pregnancy test is done to make sure the patient
isn’t pregnant; and elderly patients have an EKG
done to make sure no potential heart problems
exist. Some patients may have a stent placed prior
to the lithotripsy procedure. A stent is a plastic tube
placed in the ureter which allows the passage of
gravel and urine after the ESWL procedure is
completed.
2234

KEY TERMS
Aneurysm—A dilation of the wall of an artery
which causes a weak area prone to rupturing.
Bladder—Organ in which urine is stored prior to
urination.
Bleeding disorder—Problems in the clotting
mechanism of the blood.
Cardiologist—A physician who specializes in
problems of the heart.
EKG—A tracing of the electrical activity of the
heart.
ESWL (Extracorporeal shock wave lithotripsy)—
The use of focused shock waves, generated outside
the body, to fragment kidney stones.
Gravel—The debris which is formed from a fragmented kidney stone.
IVP (Intravenous pyelogram)—The use of a dye,
injected into the veins, used to locate kidney
stones. Also used to determine the anatomy of the
urinary system.
Kidney stone—A hard mass that forms in the
urinary tract and which can cause pain, bleeding,
obstruction, or infection. Stones are primarily made
up of calcium.
Stent—A plastic tube placed in the ureter prior to
the ESWL procedure which facilitates the passage
of gravel and urine
Ultrasound—Sound waves used to determine the
internal structures of the body
Ureter—A tube which carries urine from the kidney
to the bladder.
Urethra—A tube through which urine passes during
urination.
Urologist—A physician who specializes in problems
of the urinary system.

Aftercare
Most patients have a lot of blood in their urine after
the ESWL procedure. This is normal and should clear
after several days to a week or so. Lots of fluids should
be taken to encourage the flushing of any gravel remaining in the urinary system. The patient should follow up
with the urologist in about two weeks to make sure that
everything is going as planned. If a stent has been
inserted, it is normally removed at this time. Patients
may return to work whenever they feel able.
GALE ENCYCLOPEDIA OF MEDICINE

Liver biopsy
A lithotriptor in use by patient in tub. This noninvasive method crushes kidney stones through shock waves. (Photo Researchers,
Inc. Reproduced by permission.)

Risks
Abdominal pain is not uncommon after ESWL,
but it is usually not cause to worry. However, persistent or severe abdominal pain may imply unexpected
internal injury. Colicky renal pain is very common as
gravel is still passing. Other problems may include
perirenal hematomas (blood clots near the kidneys) in
66% of the cases; nerve palsies; pancreatitis (inflammation of the pancreas); and obstruction by stone
fragments. Occasionally, stones may not be completely fragmented during the first ESWL treatment and
further ESWL procedures may be required.
Resources

Liver-spleen scan see Liver nuclear medicine
scan

Liver biopsy
Definition
A liver biopsy is a medical procedure performed
to obtain a small piece of liver tissue for diagnostic
testing. Liver biopsies are sometimes called percutaneous liver biopsies, because the tissue sample is
obtained by going through the patient’s skin.

ORGANIZATIONS

American Urological Association. 1120 North Charles St.,
Baltimore, MD 21201-5559. (410) 727-1100. <http://
www.auanet.org/index_hi.cfm>.

Joseph Knight, PA

Live cell therapy see Cell therapy
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
A liver biopsy is usually done to diagnose a tumor,
or to evaluate the extent of damage that has occurred
to the liver because of chronic disease. Biopsies are
often performed to identify abnormalities in liver tissues after imaging studies have failed to yield clear
results.
2235

Liver biopsy

A liver biopsy may be ordered to evaluate any of
the following conditions or disorders:


Jaundice



Cirrhosis



Hemochromatosis, which is a condition of excess
iron in the liver.



Repeated abnormal results from liver function tests



Unexplained swelling or enlargement of the liver



Primary cancers of the liver, such as hepatomas,
cholangiocarcinomas, and angiosarcomas



Metastatic cancers of the liver.

A false color image of hepatocyte cells of the liver that secrete
bile. (Custom Medical Stock Photo. Reproduced by permission.)

Precautions
Some patients should not have percutaneous liver
biopsies. They include patients with any of the following conditions:


A platelet count below 60,000



A longer-than-normal prothrombin time



A liver tumor that contains a large number of blood
vessels



A history of unexplained bleeding



A watery (hydatid) cyst



An infection in either the cavity around the lungs, or
the diaphragm.

Description
Percutaneous liver biopsy is done with a special
hollow needle, called a Menghini needle, attached to a
suction syringe. Doctors who specialize in the digestive system or liver will sometimes perform liver biopsies. But in most cases, a radiologist (a doctor who
specializes in x rays and imaging studies) performs the
biopsy. The radiologist will use computed tomography scan (CT scan) or ultrasound to guide the choice
of the site for the biopsy.
An hour or so before the biopsy, the patient may
be given a sedative to help relaxation. He or she is then
asked to lie on the back with the right elbow to the side
and the right hand under the head. The patient is
instructed to lie as still as possible during the procedure. He or she is warned to expect a sensation resembling a punch in the right shoulder, but to hold still in
spite of the momentary feeling.
The doctor marks a spot on the skin where the
needle will be inserted and thoroughly cleanses the
right side of the upper abdomen with an antiseptic
2236

solution. The patient is then given an anesthetic at
the biopsy site.
The needle with attached syringe is inserted into
the patient’s chest wall. The doctor then draws the
plunger of the syringe back to create a vacuum. At
this point the patient is asked to take a deep breath,
exhale the air and hold their breath at the point of
complete exhalation. The needle is inserted into the
liver and withdrawn quickly, usually within two seconds or less. The negative pressure in the syringe
draws or pulls a sample of liver tissue into the biopsy
needle. As soon as the needle is withdrawn, the patient
can breathe normally. Pressure is applied at the biopsy
site to stop any bleeding, and a bandage will be placed
over it. The entire procedure takes 10 to 15 minutes.
Test results are usually available within a day.

Preparation
Aspirin and non-steroidal anti-inflammatory
drugs (NSAIDs) such as ibuprofen are known to thin
the blood and interfere with clotting. These medications should be avoided for at least a week before the
biopsy. Four to eight hours before the biopsy, patients
should stop eating and drinking.
The patient’s blood will be tested prior to the
biopsy to make sure that it is clotting normally. Tests
will include a platelet count and a prothrombin time.
Doctors will also ensure that the patient is not taking
any other medications, such as blood thinners like
Coumadin, that might affect blood clotting.

Aftercare
Liver biopsies are outpatient procedures in most
hospitals. After the biopsy, patients are usually
GALE ENCYCLOPEDIA OF MEDICINE

Biopsy—A procedure where a piece of tissue is
removed from a patient for diagnostic testing.
Menghini needle—A special needle used to obtain
a sample of liver tissue.
Percutaneous biopsy—A biopsy in which a needle
is inserted and a tissue sample removed through the
skin.
Prothrombin time—A blood test that determines
how quickly a person’s blood will clot.
Vital signs—A person’s essential body functions,
usually defined as the pulse, body temperature,
and breathing rate.

small chance that an infection may occur, or an internal organ such as the lung, gall bladder, or kidney
could be punctured.

Normal results
After the biopsy, the liver sample is sent to the
pathology laboratory for study under a microscope. A
normal (negative) result would find no evidence of
cancer or other disease in the tissue sample.

Abnormal results
Changes in liver tissue that are visible under the
microscope indicate abnormal results. Possible causes
for the abnormality include the presence of a tumor, or
a disease such as hepatitis.
Resources

instructed to lie on their right side for about two hours.
This provides pressure to the biopsy site and helps
prevent bleeding. A nurse will check the patient’s
vital signs at regular intervals. If there are no complications, the patient is sent home within about four to
eight hours.
Patients should arrange to have a friend or relative
take them home after discharge. Bed rest for a day is
recommended, followed by a week of avoiding heavy
work or strenuous exercise. The patient can resume
eating a normal diet.
Some mild soreness in the area of the biopsy is
normal after the anesthetic wears off. Irritation of the
muscle that lies over the liver can also cause mild
discomfort in the shoulder for some patients. Tylenol
can be taken for minor soreness, but aspirin and
NSAIDs are best avoided. Patients should call their
doctor if they have severe pain in the abdomen, chest
or shoulder, difficulty breathing, or persistent bleeding. These signs may indicate that there has been
leakage of bile into the abdominal cavity, or that air
has been introduced into the cavity around the lungs.

Risks
The risks of a liver biopsy are usually very small.
When complications do occur, over 90% are apparent
within 24 hours after the biopsy. The most significant
risk is internal bleeding. Bleeding is most likely to
occur in elderly patients, in patients with cirrhosis, or
in patients with a tumor that has many blood vessels.
Other complications from percutaneous liver biopsies
include the leakage of bile or the introduction of air
into the chest cavity (pneumothorax). There is also a
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Brown, Kyle E., et al. ‘‘Liver Biopsy: Indications,
Technique, Complications and Interpretation.’’ In
Liver Disease. Diagnosis and Management, edited by
Bruce R. Bacon and Adrian M. Di Bisceglie.
Philadelphia, PA: Churchill Livingstone, 2000.
Reddy, K. Rajender, and Lennox J. Jeffers. ‘‘Evaluation of
the Liver. Liver Biopsy and Laparoscopy.’’ In Schiff’s
Diseases of the Liver, edited by Eugene R. Schiff, et al.
Philadelphia, PA: Lippincott-Raven, 1999.
PERIODICALS

Bravo, Arturo A., et al. ‘‘Liver Biopsy’’ New England
Journal of Medicine 344, no. 7 (February 15, 2001):
495-500.

Lata Cherath, PhD

Liver cancer
Definition
Liver cancer is a relatively rare form of cancer but
has a high mortality rate. Liver cancers can be classified
into two types. They are either primary, when the cancer
starts in the liver itself, or metastatic, when the cancer
has spread to the liver from some other part of the body.

Description
Primary liver cancer
Primary liver cancer is a relatively rare disease in
the United States, representing about 2% of all
2237

Liver cancer

KEY TERMS

Liver cancer

malignancies and 4% of newly diagnosed cancers.
Hepatocellular carcinoma (HCC) is the fifth most
common cancer in the world as of 2004. It is much
more common outside the United States, representing
10% to 50% of malignancies in Africa and parts of
Asia. Rates of HCC in men are at least two to three
times higher than for women. In high–risk areas (East
and Southeast Asia, sub-Saharan Africa), men are
even more likely to have HCC than women.
According to the American Cancer Society,
18,920 people in the United States will be diagnosed
with primary liver cancer in 2004, and 14,270 persons
will die from the disease. The incidence of primary
liver cancer has been rising in the United States and
Canada since the mid-1990s, most likely as a result of
the rising rate of hepatitis C infections.
TYPES OF PRIMARY LIVER CANCER. In adults, most
primary liver cancers belong to one of two types:
hepatomas, or hepatocellular carcinomas (HCC),
which start in the liver tissue itself; and cholangiomas,
or cholangiocarcinomas, which are cancers that
develop in the bile ducts inside the liver. About 80%
to 90% of primary liver cancers are hepatomas. In the
United States, about five persons in every 200,000 will
develop a hepatoma (70% to 75% of cases of primary
liver cancers are HCC). In Africa and Asia, over
40 persons in 200,000 will develop this form of cancer
(more than 90% of cases of primary liver are HCC).
Two rare types of primary liver cancer are mixed-cell
tumors and Kupffer cell sarcomas.

One type of primary liver cancer, called a hepatoblastoma, usually occurs in children younger than four
years of age and between the ages of 12 and 15. Unlike
liver cancers in adults, hepatoblastomas have a good
chance of being treated successfully. Approximately
70% of children with hepatoblastomas experience
complete cures. If the tumor is detected early, the
survival rate is over 90%.
Metastatic liver cancer
The second major category of liver cancer, metastatic liver cancer, is about 20 times as common in
the United States as primary liver cancer. Because
blood from all parts of the body must pass through
the liver for filtration, cancer cells from other organs
and tissues easily reach the liver, where they can lodge
and grow into secondary tumors. Primary cancers in
the colon, stomach, pancreas, rectum, esophagus,
breast, lung, or skin are the most likely to metastasize
(spread) to the liver. It is not unusual for the metastatic
cancer in the liver to be the first noticeable sign of a
cancer that started in another organ. After cirrhosis,
2238

metastatic liver cancer is the most common cause of
fatal liver disease.

Causes and symptoms
Risk factors
The exact cause of primary liver cancer is still
unknown. In adults, however, certain factors are
known to place some individuals at higher risk of
developing liver cancer. These factors include:


Male sex.



Age over 60 years.



Ethnicity. Asian Americans with cirrhosis have four
times as great a chance of developing liver cancer as
Caucasians with cirrhosis, and African Americans
have twice the risk of Caucasians. In addition,
Asians often develop liver cancer at much younger
ages than either African Americans or Caucasians.



Exposure to substances in the environment that tend
to cause cancer (carcinogens). These include: a substance produced by a mold that grows on rice and
peanuts (aflatoxin); thorium dioxide, which was once
used as a contrast dye for x rays of the liver; vinyl
chloride, used in manufacturing plastics; and cigarette smoking.



Use of oral estrogens for birth control.



Hereditary hemochromatosis. This is a disorder characterized by abnormally high levels of iron storage in
the body. It often develops into cirrhosis.



Cirrhosis. Hepatomas appear to be a frequent complication of cirrhosis of the liver. Between 30% and
70% of hepatoma patients also have cirrhosis. It is
estimated that a patient with cirrhosis has 40 times
the chance of developing a hepatoma than a person
with a healthy liver.



Exposure to hepatitis viruses: Hepatitis B (HBV),
Hepatitis C (HCV), Hepatitis D (HDV), or
Hepatitis G (HGV). It is estimated that 80% of
worldwide HCC is associated with chronic HBV
infection. In Africa and most of Asia, exposure to
hepatitis B is an important factor; in Japan and some
Western countries, exposure to hepatitis C is connected with a higher risk of developing liver cancer.
In the United States, nearly 25% of patients with
liver cancer show evidence of HBV infection.
Hepatitis is commonly found among intravenous
drug abusers. The 70% increase in HCC incidence
in the United States is thought to be due to increasing
rates of HBV and HCV infections due to increased
sexual promiscuity and illicit drug needle sharing.
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms of liver cancer
The early symptoms of primary, as well as metastatic, liver cancer are often vague and not unique to
liver disorders. The long period between the beginning
of the tumor’s growth and the first signs of illness is the
major reason why the disease has such a high mortality
rate. At the time of diagnosis, patients are often fatigued, with fever, abdominal pain, and loss of appetite.
They may look emaciated and generally ill. As the
tumor enlarges, it stretches the membrane surrounding the liver (the capsule), causing pain in the upper
abdomen on the right side. The pain may extend into
the back and shoulder. Some patients develop a collection of fluid, known as ascites, in the abdominal cavity. Others may show signs of bleeding into the
digestive tract. In addition, the tumor may block the
ducts of the liver or the gall bladder, leading to jaundice. In patients with jaundice, the whites of the eyes
and the skin may turn yellow, and the urine becomes
dark–colored.

levels. Tests for alkaline phosphatase, bilirubin, lactic
dehydrogenase, and other chemicals indicate that the
liver is not functioning normally. About 75% of
patients with liver cancer show evidence of hepatitis
infection. Again, however, abnormal liver function
test results are not specific for liver cancer.
Imaging studies
Imaging studies are useful in locating specific
areas of abnormal tissue in the liver. Liver tumors as
small as an inch across can now be detected by ultrasound or computed tomography scan (CT scan).
Imaging studies, however, cannot tell the difference
between a hepatoma and other abnormal masses or
lumps of tissue (nodules) in the liver. A sample of liver
tissue for biopsy is needed to make the definitive diagnosis of a primary liver cancer. CT or ultrasound can
be used to guide the doctor in selecting the best location for obtaining the biopsy sample.
Chest x rays may be used to see whether the liver
tumor is primary or has metastasized from a primary
tumor in the lungs.
Liver biopsy

Diagnosis
Physical examination
If the doctor suspects a diagnosis of liver cancer,
he or she will check the patient’s history for risk factors and pay close attention to the condition of the
patient’s abdomen during the physical examination.
Masses or lumps in the liver and ascites can often be
felt while the patient is lying flat on the examination
table. The liver is usually swollen and hard in patients
with liver cancer; it may be sore when the doctor
presses on it. In some cases, the patient’s spleen is
also enlarged. The doctor may be able to hear an
abnormal sound (bruit) or rubbing noise (friction
rub) if he or she uses a stethoscope to listen to the
blood vessels that lie near the liver. The noises are
caused by the pressure of the tumor on the blood
vessels.
Laboratory tests
Blood tests may be used to test liver function or to
evaluate risk factors in the patient’s history. Between
50% and 75% of primary liver cancer patients have
abnormally high blood serum levels of a particular
protein (alpha-fetoprotein or AFP). The AFP test,
however, cannot be used by itself to confirm a diagnosis of liver cancer, because cirrhosis or chronic
hepatitis can also produce high alpha–fetoprotein
GALE ENCYCLOPEDIA OF MEDICINE

Liver biopsy is considered to provide the definite
diagnosis of liver cancer. A sample of the liver or tissue
fluid is removed with a fine needle and is checked
under a microscope for the presence of cancer cells.
In about 70% of cases, the biopsy is positive for cancer. In most cases, there is little risk to the patient from
the biopsy procedure. In about 0.4% of cases, however, the patient develops a fatal hemorrhage from the
biopsy because some tumors are supplied with a large
number of blood vessels and bleed very easily.
Laparoscopy
The doctor may also perform a laparoscopy to
help in the diagnosis of liver cancer. First, the doctor
makes a small cut in the patient’s abdomen and inserts
a small, lighted tube called a laparoscope to view the
area. A small piece of liver tissue is removed and
examined under a microscope for the presence of cancer cells.

Treatment
Treatment of liver cancer is based on several factors, including the type of cancer (primary or metastatic); stage (early or advanced); the location of other
primary cancers or metastases in the patient’s body;
the patient’s age; and other coexisting diseases, including cirrhosis. For many patients, treatment of liver
2239

Liver cancer

The association between HDV and HGV and HCC is
unclear at this time.

Liver cancer

cancer is primarily intended to relieve the pain caused
by the cancer but cannot cure it.
Surgery
Few liver cancers in adults can be cured by surgery
because they are usually too advanced by the time they
are discovered. If the cancer is contained within one
lobe of the liver, and if the patient does not have either
cirrhosis, jaundice, or ascites, surgery is the best
treatment option. Patients who can have their entire
tumor removed have the best chance for survival.
Unfortunately, only about 5% of patients with metastatic cancer (from primary tumors in the colon or
rectum) fall into this group. If the entire visible
tumor can be removed, about 25% of patients will be
cured. The operation that is performed is called a
partial hepatectomy, or partial removal of the liver.
The surgeon will remove either an entire lobe of the
liver (a lobectomy) or cut out the area around the
tumor (a wedge resection).
A newer technique that is reported to be safe and
effective is laparoscopic radiofrequency ablation
(RFA). RFA is a technique in which the surgeon
places a special needle electrode in the tumor under
guidance from MRI or CT scanning. When the electrode has been properly placed, a radiofrequency current is passed through it, heating the tumor and killing
the cancer cells. RFA can be used to treat tumors that
are too small or too inaccessible for removal by conventional open surgery.

liver cancer, however, is only to give short–term relief
from some of the symptoms. Liver cancers are not
sensitive to radiation, and radiation therapy will not
prolong the patient’s life.
Liver transplantation
Removal of the entire liver (total hepatectomy)
and liver transplantation can be used to treat liver
cancer. However, there is a high risk of tumor recurrence and metastases after transplantation. In addition, most patients have cancer that is too far
advanced at the time of diagnosis to benefit from
liver transplantation.
Other therapies
Other therapeutic approaches include:


Hepatic artery embolization with chemotherapy
(chemoembolization).



Alcohol ablation via ultrasound-guided percutaneous injection.



Ultrasound-guided cryoablation.



Immunotherapy with monoclonal antibodies tagged
with cytotoxic agents.



Gene therapy with retroviral vectors containing
genes expressing cytotoxic agents.

Alternative treatment
Chemotherapy
Some patients with metastatic cancer of the liver
can have their lives prolonged for a few months by
chemotherapy, although cure is not possible. If the
tumor cannot be removed by surgery, a tube (catheter)
can be placed in the main artery of the liver and an
implantable infusion pump can be installed. The pump
allows much higher concentrations of the cancer drug to
be carried to the tumor than is possible with chemotherapy carried through the bloodstream. The drug that is
used for infusion pump therapy is usually floxuridine
(FUDR), given for 14-day periods alternating with 14day rests. Systemic chemotherapy can also be used to
treat liver cancer. The medications usually used are 5fluorouracil (Adrucil, Efudex) or methotrexate (MTX,
Mexate). Systemic chemotherapy does not, however,
significantly lengthen the patient’s survival time.
Radiation therapy
Radiation therapy is the use of high-energy rays or
x rays to kill cancer cells or to shrink tumors. Its use in
2240

Many patients find that alternative and complementary therapies help to reduce the stress associated
with illness, improve immune function, and boost
spirits. While there is no clinical evidence that these
therapies specifically combat disease, activities such as
biofeedback, relaxation, therapeutic touch, massage
therapy and guided imagery have no side effects and
have been reported to enhance well–being.
Several other healing therapies are sometimes
used as supplemental or replacement cancer treatments, such as antineoplastons, cancell, cartilage
(bovine and shark), laetrile, and mistletoe. Many of
these therapies have not been the subject of safety and
efficacy trials by the National Cancer Institute (NCI).
The NCI has conducted trials on cancell, laetrile, and
other alternative therapies and found no anticancer
activity. These treatments have varying effectiveness
and safety considerations. Patients using any alternative remedy should first consult their doctor in order
to prevent harmful side effects or interactions with
traditional cancer treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Aflatoxin—A substance produced by molds that
grow on rice and peanuts. Exposure to aflatoxin is
thought to explain the high rates of primary liver
cancer in Africa and parts of Asia.
Alpha-fetoprotein—A protein in blood serum that
is found in abnormally high concentrations in most
patients with primary liver cancer.
Cirrhosis—A chronic degenerative disease of the
liver, in which normal cells are replaced by fibrous
tissue. Cirrhosis is a major risk factor for the later
development of liver cancer.
Cryoablation—A technique for removing cancerous tissue by killing it with extreme cold.
Hepatitis—A viral disease characterized by inflammation of the liver cells (hepatocytes). People
infected with hepatitis B or hepatitis C virus are at
an increased risk for developing liver cancer.
Metastatic cancer—A cancer that has spread to an
organ or tissue from a primary cancer located elsewhere in the body.
Radiofrequency ablation—A technique for removing a tumor by heating it with a radiofrequency
current passed through a needle electrode.

Prognosis
Liver cancer has a very poor prognosis because it
is often not diagnosed until it has metastasized. Fewer
than 10% of patients survive three years after the
initial diagnosis; the overall five-year survival rate
for patients with hepatomas is around 4%. Most
patients with primary liver cancer die within six
months of diagnosis, usually from liver failure; fewer
than 5% are cured of the disease. Patients with liver
cancers that metastasized from cancers in the colon
live slightly longer than those whose cancers spread
from cancers in the stomach or pancreas.
As of 2004, African American and Hispanic patients
have much lower 5-year survival rates than Caucasian
patients. It is not yet known, however, whether cultural
differences as well as biological factors may be partly
responsible for the variation in survival rates.

Prevention
There are no useful strategies at present for
preventing metastatic cancers of the liver. Primary
liver cancers, however, are 75% to 80% preventable.
GALE ENCYCLOPEDIA OF MEDICINE

Current strategies focus on widespread vaccination
for hepatitis B, early treatment of hereditary hemochromatosis, and screening of high-risk patients
with alpha–fetoprotein testing and ultrasound
examinations.
Lifestyle factors that can be modified in order to
prevent liver cancer include avoidance of exposure to
toxic chemicals and foods harboring molds that produce aflatoxin. Most important, however, is avoidance of alcohol and drug abuse. Alcohol abuse is
responsible for 60% to 75% of cases of cirrhosis,
which is a major risk factor for eventual development
of primary liver cancer. Hepatitis is a widespread disease among persons who abuse intravenous drugs.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Primary Liver Cancer.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Berber, E., A. Senagore, F. Remzi, et al. ‘‘Laparoscopic
Radiofrequency Ablation of Liver Tumors Combined
with Colorectal Procedures.’’ Surgical Laparoscopy,
Endoscopy and Percutaneous Techniques 14 (August
2004): 186–190.
Cahill, B. A., and D. Braccia. ‘‘Current Treatment for
Hepatocellular Carcinoma.’’ Clinical Journal of
Oncology Nursing 8 (August 2004): 393–399.
Decadt, B., and A. K. Siriwardena. ‘‘Radiofrequency
Ablation of Liver Tumours: Systematic Review.’’
Lancet Oncology 5 (September 2004): 550–560.
Harrison, L. E., T. Reichman, B. Koneru, et al. ‘‘Racial
Discrepancies in the Outcome of Patients with
Hepatocellular Carcinoma.’’ Archives of Surgery 139
(September 2004): 992–996.
Nguyen, M. H., A. S. Whittemore, R. T. Garcia, et al. ‘‘Role
of Ethnicity in Risk for Hepatocellular Carcinoma in
Patients with Chronic Hepatitis C and Cirrhosis.’’
Clinical Gastroenterology and Hepatology 2 (September
2004): 820–824.
Stuart, Keith E., MD. ‘‘Hepatic Carcinoma, Primary.’’
eMedicine July 20, 2004. <http://www.emedicine.com/
med/topic2664.htm>.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta,
GA 30329. (800) 227-2345. <http://www.cancer.org>.
American Institute for Cancer Research (AICR). 1759 R St.
NW, Washington, DC 20009. (800) 843-8114. <http://
www.aicr.org>.
American Liver Foundation.1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
2241

Liver cancer

KEY TERMS

Liver disease

Cancer Care, Inc. 275 Seventh Ave., New York, NY
10001.(800) 813-HOPE. <http://
www.cancercare.org>.
Cancer Hope Network. Suite A., Two North Rd., Chester,
NJ 07930. (877) HOPENET. <http://
www.cancerhopenetwork.org>.
Hospicelink. Hospice Education Institute, 190 Westbrook
Rd., Essex, CT, 06426-1510. (800) 331-1620. <http://
www.hospiceworld.com>.
National Cancer Institute (National Institutes of Health).
9000 Rockville Pike, Bethesda, MD 20892. (800)
422-6237. <http://www.nci.nih.gov>.
Wellness Community. Suite 412, 35 E. Seventh St.,
Cincinnati, OH 45202. (888) 793-9355. <http://
www.wellness-community.org>.

blood is rich in nutruents (food, vitamins, and minerals) that the body needs to function. Some of the most
important functions of the liver are to process these
nutrients.
Important functions of the liver include:


manufacturing and regulating the production of proteins. The most important proteins made in the liver
are albumin, which helps maintain blood volume,
and clotting factors to help regulate blood clotting.



making and storing fatty acids and cholesterol.



forming and releasing bile



processing and storing sugars in the form of glycogen, which can then be re-converted into energy



Storing iron, an important element in blood
formation



Breaking down (detoxifying) alcohol, drugs, and
environmental poisons so that they can be removed
from the body.



Processing and removing bilirubin, a product
released when red blood cells break down, and
ammonia, a toxic waste product of protein
breakdown.



Defending against infection by removing bacteria
from the blood and making chemicals necessary to
the functioning of the immune system.

OTHER

American Cancer Society (ACS). Cancer Facts & Figures
2004. <http://www.cancer.org/downloads/STT/
CAFF_finalPWSecured.pdf>.

Rebecca J. Frey, PhD
Laura Ruth, PhD

Liver cirrhosis see Cirrhosis

Liver disease
Definition
Liver disease is a general term for any damage that
reduces the functioning of the liver.

Description
The liver is a large, solid organ located in the
upper right-hand side of the abdomen. Most of the
liver lies under the rib cage, which helps protect it from
physical injury. The liver is made up of two main lobes
and two minor lobes and has a total weight in adults of
about 3.5 lb (1.6 kg).
Within the liver are tiny ducts (tubes) that collect
bile, a product secreted by the liver. Bile is stored in to
the gall bladder and then released into the intestines
after meals to help in the digestion of fats and the
absorption of certain vitamins. This system of bile production by the liver, transport through the bile ducts,
and storage in the gall bladder is called the biliary
system. Damage to this system is called biliary disease.
The liver receives blood that comes directly from
the intestines. At any given time the liver contains
about 13% of the blood circulating in the body. This
2242

Although the liver is the only organ that has the
capacity to grow back, or regenerate, after injury or
damage, sometimes the damage is too great for it
to heal. The American Association for the Study
of Liver Disease estimates that about 25 million
Americans experience a liver-related disease each
year. Individuals cannot live without a functioning
liver. The ability to transplant livers is improving,
liver transplantation is not nearly as common or
successful as kidney transplantation.
Because the liver has many vital functions, there
are many types of liver disease. The American Liver
Foundation estimates that over 20,000 Americans die
of chronic liver disease each year and another 360,000
are hospitalized. Individuals cannot live without a
functioning liver.
Congenital Liver Diseases
Congenital liver diseases are disorders that are
present at birth. Inherited liver diseases and disorders
include:


Alagile syndrome, a disorder that causes withering of
the bile ducts. This disease occurs in less than 1 in
100,000 individuals.
GALE ENCYCLOPEDIA OF MEDICINE

Alpha 1-antitrypsin deficiency, an inborn error in
metabolism and the most common type of genetic
liver disease.



Galactosemia, a hereditary metabolic disease in
which the liver is unable to break down the sugar
galactose found in milk. It occurs in about one in
every 20,000 births.



Hematochromatosis, a hereditary metabolic disorder in which too much iron is absorbed from the
diet and stored in the liver. This disease affects over
one million Americans.



Porphyria, a disorder in which the component of
blood that contains iron is not correctly formed.



Tyrosinemia, a rare inherited error in metabolism
that causes severe liver disease in infants and children. It affects fewer than 200,000 individuals in the
United States.



Type I glycogen storage disease, a lack of the enzyme
that helps regulate blood glucose (sugar) levels.



Wilson’s disease, an inherited disorder in which copper is accumulated in the liver and nervous system.
Acquired Liver Diseases

Many liver diseases are acquired from infection and
exposure of the liver to toxic substances such as alcohol
or drugs. In some areas of the world (although not the
United States) liver parasites are a common cause of
liver disease. In the United States, the most common
acquired liver diseases are hepatitis A, B, and C and
cirrhosis. Hepatitis A causes an acute (short-term) illness and is caused by a virus found in food or drinking
water contaminated with feces. Hepatitis A infects
between 125,000 and 250,000 people in the United
States each year and causes about 100 deaths annually.
Hepatitis B is a viral infection spread by blood
exchange and sexual contact with an infected person.
It can be passed from an infected mother to her fetus.
In most people hepatitis B is a short-term illness that
causes mild symptoms such as fatigue, but in 2–6% of
people, the disease lasts a long time and causes permanent liver damage. More than 75,000 people in the
United States become infected with hepatitis B each
year. Chinese Americans have a hepatitis B infection
rate five times that of Caucasian Americans.
Hepatitis C is caused by a virus spread mainly
through contact with the blood of an infected person,
such as through sharing needles to inject drugs or from
a mother to a fetus. Individuals infected with hepatitis
C virus may not feel sick or know that they are infected
for many years, but the disease can increase the likelihood of developing liver cancer of cirrhosis. The
GALE ENCYCLOPEDIA OF MEDICINE

American Liver Foundation estimates that 4 million
Americans are infected with hepatitis C, resulting in
10,000–12,000 deaths each year. About 70% of individuals who are infected do not know that they have
the virus. African Americans have the highest rate of
hepatitis C infections and are twice as likely to be
infected with hepatitis C as Caucasian Americans.
Cirrhosis of the liver involves the formation of
permanent scar tissue in the liver and loss of liver
function. It is often caused by chronic alcohol abuse
(alcoholic liver disease), but it can also be caused by
diseases such as hepatitis. Cirrhosis interferes with
blood flow through the liver and can raise pressure in
blood vessels supplying the liver and decrease the
absorption of nutrients from the blood, leading to
malnutrition. The liver of individuals with cirrhosis is
also less effective in removing toxic wastes from the
blood. Cirrhosis can be fatal.
Over 800 over-the-counter and prescription
drugs, as well as illicit street drugs, can cause liver
damage. One of the most common drugs to cause
liver damage is acetaminophen (Tylenol) when taken
at high doses or by individuals who already have some
liver damage. Exposure to toxic chemicals, physical
injury, and blockage of the bile ducts call also cause
liver damage.
Liver cancer can either develop first in the liver
(primary liver cancer) or spread there from another
site (metastasized cancer). About 16,000 new cases of
primary liver cancer are diagnosed each year, most
commonly in middle age and older men. Although the
cause of liver cancer is unclear, it appears to be associated with chronic infections of hepatitis B and C.

Causes & symptoms
The causes of liver disease are many and varied.
Leading causes are viral infection, alcohol abuse, and
inherited disease. A common symptoms of liver disease are jaundice. With jaundice, the skin and the
whites of the eyes take on a yellowish color as a result
of the accumulation of bilirubin and bile pigments in
the blood. This is a sign that the liver or the biliary
system is not functioning properly. Other symptoms of
liver disease include an enlarged liver and swollen
abdomen, nausea, vomiting, weight loss, and fatigue.
Some infections cause flu-like symptoms of fever,
headache, and weakness.

Diagnosis
Liver function tests, sometimes called a liver panel,
measure various enzymes, proteins, and waste
2243

Liver disease



Liver disease

products in the blood. These readings can tell a physician whether the liver is damaged and give an idea of
how well it is functioning. Liver function tests are the
most common way to diagnose liver damage. Based on
the results of a liver panel, additional blood tests for
infection, a liver biopsy, or liver scan may be done to
pinpoint the reason for loss of function.

Treatment
Treatments depend on the type of liver disease an
individual has. Many liver diseases are treated with
altered diets, abstinence from alcohol, and medication.
Hepatitis can be treated with antiviral medications
such as interferon or ribavirin. Liver cancer is treated
with chemotherapy, radiation, and surgery. As of 2005,
over 300 clinical trials were enrolling patients with
various types of liver disease in experimental treatment programs. Information on current clinical trials
can be found at <http://www.clinicaltrials.gov>.
If the liver fails completely, a liver transplant is
possible. About 5,600 liver transplants were performed in the United States in 2003. Donors and
recipients are matched on the basis of blood type and
must also be about the same weight. There is no
machine like a kidney dialysis machine to perform
the functions of the liver while individuals are awaiting
a transplant. In 2003, 1,800 people died awaiting a
liver donor, and about 18,000 more are on the waiting
list awaiting a donated liver. Livers to be transplanted
can come from either a living donor or a deceased
donor.

Alternative treatment
A great deal of interest in alternative treatments
for hepatitis C has resulted in a review of alternative
and complementary treatments by the National
Center for Complementary and Alternative Medicine
(NCCAM), a division of the United States National
Institutes of Health. Although there was in 2003 not
enough solid experimental evidence to show that any
herbal treatments cured hepatitis C, the most promising herbal treatment was an extract of milk thistle
(Silybum marianum), a plant in the aster family that
has been used for centuries in Europe to treat liver
disease and jaundice. Some studies suggested that
extracts of milk thistle promoted the growth of certain
types of liver cells and acted as an anti-oxidant to
protect the liver while producing few unwanted side
effects. Other studies showed no protective effects.
Licorice root (Glycyrrhiza glabra) was also
reviewed by NCCAM. Some studies suggested that
2244

KEY TERMS
Biliary—Relating to the system that produces and
transports bile.
Bile—A yellowish-green material secreted by the
liver, stored by the gall bladder, and emptied into
the small intestine to aid in the digestion and
absorption of fats.
Bilirubin—A reddish-yellow substance that results
from the breakdown of aging red blood cells. It is
found in blood and bile, and if it accumulates in
large quantities can cause jaundice.
Biopsy—A diagnostic procedure in which a small
sample of tissue is obtained and examined under
the microscope to determine they type and stage of
a disease.
Congenital—Present at birth.
Feces—Waste products eliminated from the large
intestine; excrement.
Jaundice—A yellowish tinge to the skin and whites
of the eyes that indicates malfunction of the biliary
system and/or liver and build up of bile components in the blood.

licorice root had antiviral properties, however this
herb did not reduce the amount of hepatitis C virus
circulating in the blood. Long term use of licorice root
can have serious, health-threatening side effects.
Other alternative treatments studied by NCCAM
include ginseng (Panax quinquefolius and Panax ginseng), which they concluded might possibly have a
positive effect on the liver, especially in the elderly,
and schisandra (Schisandra chinensis and Schisandra
sphenanthera) used in Chinese medicine, which seemed
to have a liver-protective effect in laboratory animals.
Thymus extract and colloidal silver were found to be
ineffective in treating liver disease.

Prognosis
The course of liver disease depends on the type of
disease. Many individuals recover completely from
infections of hepatitis A and B. However, if liver scarring occurs, the effects are irreversible. The initial
success rate for liver transplants is good, with about
90% of individuals receiving a liver transplant are
alive one year after the transplant operation.
However, no alternative treatments produced a better
outcome than traditional treatments of hepatitis C.
GALE ENCYCLOPEDIA OF MEDICINE

Description

Prevention is an effective way to avoid liver disease. Vaccines exist for hepatitis A and B (but not
hepatitis C), although many individuals remain unvaccinated. In addition to vaccination, individuals can
decrease the likelihood of developing liver disease by


practicing safe sex



avoiding sharing needles



eating a healthy, balanced diet



taking medications as prescribed



avoiding drinking alcohol.

A normally functioning liver metabolizes and
detoxifies substances formed in the body during the
digestive process. Impaired liver function allows substances like ammonia (formed when the body digests
protein), some fatty acids, phenol, and mercaptans to
escape into the bloodstream. From there, they may
penetrate the blood-brain barrier, affect the central
nervous system (CNS), and lead to hepatic coma.
Hepatic coma is most common in patients with
chronic liver disease. It occurs in 50-70% of all those
with cirrhosis.

Causes and symptoms

Resources
ORGANIZATIONS

American Association for the Study of Liver Disease, 1729
King Street, Suite 200, Alexandria, VA 22314.
Telephone: 703-299-9766. <http://www.aasld.org>.
American Liver Foundation, 75 Maiden Lane, Suite 603,
New York, NY 10038. Telephone: 800-465-4837 or
888-443-7872. <http://www.liverfoundation.org>.
OTHER

‘‘Hepatitis C and Complementary and Alternative
Medicine: 2003 Update’’ National Center for
Complementary and Alternative Medicine. 11 January
2005 [cited 25 March 2005]/ <http://nccam.nih.gov/
health/hepatitsc>.
‘‘Liver Disease’’ Medline Plus Medical Encyclopedia 16 July
2004 [cited 25 March 2005]. United States National
Library of Medicine and the National Institutes of
Health. <http://www.mln.nih.gov/medlineplus/ency/
article/000205.htm>.
‘‘Liver Function Test Factsheet’’ liverfoundation.org. 2003
[cited 23 March 2005]. <http://www.liverfoundation.
org/db/articles/1077>.

Tish Davidson, A.M.

The cause of hepatic coma is unknown, but the
condition is frequently associated with the following
conditions:


Acute or chronic liver disease



Gastrointestinal bleeding



Azotemia, the accumulation of nitrogen-containing
compounds (such as urea) in the blood



Inherited disorders that disrupt the process by which
nitrogen is decomposed and excreted



The use of shunts (devices implanted in the body to
redirect the flow of fluid from one vessel to another)



Electrolyte imbalances, including low levels of potassium (hypokalemia) and abnormally alkaline blood
pH (alkalosis). These imbalances may result from the
overuse of sedatives, analgesics, or diuretics; reduced
levels of oxygen (hypoxia), or withdrawal of excessive amounts of body fluid (hypovolemia)



Constipation, which may increase the body’s nitrogen load



Surgery



Infection



Acute liver disease.

Binge drinking and acute infection are common
causes of hepatic coma in patients with long-standing
liver disease.

Liver encephalopathy
Definition
Liver encephalopathy is a potentially life-threatening disease in which toxic substances accumulate
in the blood. Also known as hepatic encephalopathy
or hepatic coma, this condition can cause confusion,
disorientation, abnormal neurological signs, loss of
consciousness, and death.
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms of hepatic encephalopathy range from
almost unnoticeable changes in personality, energy
levels, and thinking patterns to deep coma.
Inability to reproduce a star or other simple
design (apraxia) and deterioration of handwriting
are common symptoms of early encephalopathy.
Decreased brain function can also cause inappropriate
behavior, lack of interest in personal grooming, mood
swings, and uncharacteristically poor judgment.
2245

Liver encephalopathy

Prevention

Liver encephalopathy

The patient may be less alert than usual and
develop new sleep patterns. Movement and speech
may be slow and labored.
As the disease progresses, patients become confused, drowsy, and disoriented. The breath and urine
acquires a sweet, musky odor. The hands shake, the
outstretched arms flap (asterixis or ‘‘liver flap’’), and
the patient may lapse into unconsciousness. As coma
deepens, reflexes may be heightened (hyperreflexia).
The toes sometimes splay when the sole of the foot is
stroked (Babinski reflex).
Agitation occasionally occurs in children and in
adults who suddenly develop severe symptoms.
Seizures are uncommon.

Diagnosis
The absence of sensitive, reliable tests for encephalopathy make the physician’s personal observations and professional judgment the most valuable
diagnostic tools.
Confusion, disorientation, and other indications of
impaired brain function strongly suggest encephalopathy in patients known to have liver disease. CAT scans
and examination of spinal fluid don’t provide diagnostic
clues. Elevated arterial ammonia levels are almost
always present in hepatic coma, but levels are not necessarily correlated with the severity or extent of the disease.
Magnetic resonance imaging (MRI) can show
severe brain swelling that often occurs prior to coma,
and electroencephalography (EEG) detects abnormal
brain waves even in patients with early, mild symptoms. Blood and urine analyses can provide important
information about the cause of encephalopathy in
patients suspected of taking large quantities of sedatives or other drugs.

Treatment
This condition may disappear if the cause of symptoms is eliminated. In other cases, treatment is designed
to improve liver function as much as possible; remove
or relieve factors that worsen symptoms; and decrease
the body’s production of poisonous substances.
All non-essential medications are discontinued.
Soft restraints are recommended in place of sedatives
for patients who become agitated.
Enemas or laxatives are used to stimulate expulsion of toxic intestinal products. All or most protein is
eliminated from the diet, and supplemental feeding
may be necessary to replenish lost calories. Regular
doses of neomycin (Neobiotic), taken orally or
2246

KEY TERMS
Cirrhosis—A serious disease of the liver caused by
chronic damage to its cells and the eventual formation of scar tissue (fibrosis).
Coma—A condition of deep unconsciousness from
which the person cannot be aroused
Electrolytes—Substances that conduct electricity
when they are in solution. In the body, electrolytes
in the blood and tissues enable nerve impulses to
flow normally.
Encephalopathy—A dysfunction of the brain.
Hepatic encephalopathy is brain dysfunction that
occurs because the liver isn’t removing harmful
substances from the blood.

administered to comatose patients in liquid form
through a tube, may be used to decrease production
of protein-digesting bacteria in the bowel.
Lactulose, a synthetic sugar, changes the characteristics of intestinal bacteria, decreases the amount
of ammonia accumulated in the body, and has laxative properties. The patient is given hourly doses of
lactulose syrup until diarrhea occurs, then dosage
is adjusted to maintain regular bowel function.
Lactulose and dietary-protein restrictions may be
used to control chronic encephalopathy.

Prognosis
Encephalopathy may be reversible if the responsible factor is identified and removed or treated.
Patients whose condition is the result of chronic liver
disease may recover completely after the underlying
cause is corrected.
Despite intensive treatment, encephalopathy
caused by acute liver inflammation (fulminant hepatitis) is fatal for as many as 80% of patients. Those with
chronic liver failure often die in hepatic coma.
Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.

Maureen Haggerty

Liver fluke infections see Fluke infections
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Liver function tests, or LFTs, include tests for
bilirubin, a breakdown product of hemoglobin, and
ammonia, a protein byproduct that is normally converted into urea by the liver before being excreted by
the kidneys. LFTs also commonly include tests to
measure levels of several enzymes, which are special
proteins that help the body break down and use (metabolize) other substances. Enzymes that are often measured in LFTs include gamma-glutamyl transferase
(GGT); alanine aminotransferase (ALT or SGPT);
aspartate aminotransferase (AST or SGOT); and
alkaline phosphatase (ALP). LFTs also may include
prothrombin time (PT), a measure of how long it takes
for the blood to clot.

Purpose
Liver function tests are used to aid in the differential diagnosis of liver disease and injury, and to help
monitor response to treatment.

Precautions
Bilirubin: Drugs that may cause increased blood
levels of total bilirubin include anabolic steroids,
antibiotics, antimalarials, ascorbic acid, Diabinese,
codeine, diuretics, epinephrine, oral contraceptives,
and vitamin A.
Ammonia: Muscular exertion can increase ammonia levels, while cigarette smoking produces significant increases within one hour of inhalation. Drugs
that may cause increased levels include alcohol,
barbiturates, narcotics, and diuretics. Drugs that may
decrease levels include broad-spectrum antibiotics,
levodopa, lactobacillus, and potassium salts.
ALT: Drugs that may increase ALT levels include
acetaminophen, ampicillin, codeine, dicumarol, indomethacin, methotrexate, oral contraceptives, tetracyclines, and verapamil. Previous intramuscular injections
may cause elevated levels.
GGT: Drugs that may cause increased GGT levels
include alcohol, phenytoin, and phenobarbital. Drugs
that may cause decreased levels include oral
contraceptives.

Description
The liver is one of the most important organs in
the body. As the body’s ‘‘chemical factory,’’ it
GALE ENCYCLOPEDIA OF MEDICINE

Liver function tests are used to determine if the
liver has been damaged or its function impaired.
Elevations of certain liver tests in relation to others
aids in that determination. For example, aminotransferases (which include ALT and AST) are notably
elevated in liver damage caused by liver cell disease
(hepatocellular disease). However, in intrahepatic
obstructive disease–which may be caused by some
drugs or biliary cirrhosis–the alkaline phosphatases
are most abnormal.
Alanine aminotransferase
Alanine aminotransferase (ALT), formerly called
serum glutamate pyruvate transaminase, or SGPT, is
an enzyme necessary for energy production. It is present in a number of tissues, including the liver, heart,
and skeletal muscles, but is found in the highest concentration in the liver. Because of this, it is used in
conjunction with other liver enzymes to detect liver
disease, especially hepatitis or cirrhosis without jaundice. Additionally, in conjunction with the aspartate
aminotransferase test (AST), it helps to distinguish
between heart damage and liver tissue damage.
Aspartate aminotransferase
Aspartate aminotransferase (AST), formerly
called serum glutamic-oxaloacetic transaminase, or
SGOT, is another enzyme necessary for energy production. It, too, may be elevated in liver and heart
disease. In liver disease, the AST increase is usually
less than the ALT increase. However, in liver disease
caused by alcohol use, the AST increase may be two or
three times greater than the ALT increase.
Alkaline phosphatase
Alkaline phosphatase (ALP) levels usually include
two similar enzymes (isoenzymes) that mainly come
from the liver and bone and from the placenta in
pregnant women. In some cases, doctors may order a
test to differentiate between the alkaline phosphatase
that originates in the liver and the alkaline phosphatase originating in bone. If a person has elevated ALP,
does not have bone disease and is not pregnant, he or
she may have a problem with the biliary tract, the
system that makes and stores bile. (Bile is made in
the liver, then passes through ducts to the gall bladder,
where it is stored.)
2247

Liver function tests

Liver function tests

regulates the levels of most of the main blood chemicals and acts with the kidneys to clear the blood of
drugs and toxic substances. The liver metabolizes
these products, alters their chemical structure, makes
them water soluble, and excretes them in bile.

Liver function tests

Aftercare

Gamma-glutamyl transferase
Gamma-glutamyl transferase (GGT), sometimes
called gamma-glutamyl transpeptidase (GGPT), is an
enzyme that is compared with ALP levels to distinguish between skeletal disease and liver disease.
Because GGT is not increased in bone disorders, as
is ALP, a normal GGT with an elevated ALP would
indicate bone disease. Conversely, because the GGT is
more specifically related to the liver, an elevated GGT
with an elevated ALP would strengthen the diagnosis
of liver or bile-duct disease. The GGT has also been
used as an indicator of heavy and chronic alcohol use,
but its value in these situations has been questioned
recently. It is also commonly elevated in patients with
infectious mononucleosis.
Bilirubin
Bilirubin, a breakdown product of hemoglobin, is
the predominant pigment in a substance produced by
the liver called bile. Excess bilirubin causes yellowing of
body tissues (jaundice). There are two tests for bilirubin: direct-reacting (conjugated) and indirect-reacting
(unconjugated). Differentiating between the two is
important diagnostically, as elevated levels of indirect
bilirubin are usually caused by liver cell dysfunction
(e.g. hepatitis), while elevations of direct bilirubin
typically result from obstruction either within the liver
(intrahepatic) or a source outside the liver (e.g. gallstones or a tumor blocking the bile ducts). Bilirubin
measurements are especially valuable in newborns, as
extremely elevated levels of unconjugated bilirubin can
accumulate in the brain, causing irreparable damage.

Because many patients with liver disease have
prolonged clotting times, it is important to monitor
the puncture site for bleeding after blood is drawn
(venipuncture).

Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or
feeling lightheaded after venipuncture, or hematoma
(blood accumulating under the puncture site).

Normal results
Reference ranges vary from laboratory to laboratory and also depend upon the method used. However,
normal values can generally be found within the following ranges, unless specified differently.


ALT: 5-35 IU/L (values for the elderly may be
slightly higher, and values also may be higher in
men and in African-Americans)



AST: 0-35 IU/L



ALP: 30-120 IU/L



GGT: Normal values for this test vary widely, depending on the laboratory performing the test, and the age
and sex of the patient. For example, females less than
45 years old have lower values than both males and
females over 45 years of age. Values in the newborn
can be as much as five times higher than in adults.



Bilirubin: (Adult, elderly, and child) Total bilirubin:
0.1-1.0 mg/dL; indirect bilirubin: 0.2-0.8 mg/dL; direct
bilirubin: 0.1-0.3 mg/dL. (Newborn) Total bilirubin:
1-12 mg/dL. Note: critical values for adult: greater
than 1.2 mg/dL. Critical values for newborn (requiring
immediate treatment): greater than 15 mg/dL.



Ammonia: Normal values for this test vary widely,
depending upon the laboratory performing the test,
the age of the patient, and the type of specimen. For
example, values are somewhat higher in arterial than
in venous blood.



PT: 9-12 seconds.

Ammonia
Analysis of blood ammonia aids in the diagnosis
of severe liver diseases and helps to monitor the course
of these diseases. Together with the AST and the ALT,
ammonia levels are used to confirm a diagnosis of
Reye’s syndrome (a rare disorder usually seen in children and associated with aspirin intake), which is
characterized by brain and liver damage following an
upper respiratory tract infection, chickenpox, or influenza. Ammonia levels are also helpful in the diagnosis
and treatment of hepatic encephalopathy, a serious
brain condition caused by the accumulated toxins
that result from liver disease and liver failure.

Preparation
Preparation requirements for all these tests vary
from laboratory to laboratory, so it is generally considered best that the patient be in a fasting state (nothing to
eat or drink) after midnight the day before the test(s).
2248

Abnormal results
ALT: Values are significantly increased in cases of
hepatitis, and moderately increased in cirrhosis, liver
tumor, obstructive jaundice, and severe burns. Values
are mildly increased in pancreatitis, heart attack, infectious mononucleosis, and shock. Most useful when
compared with ALP levels.
GALE ENCYCLOPEDIA OF MEDICINE

Cirrhosis—A serious disease of the liver caused by
chronic damage to its cells and the eventual formation
of scar tissue (fibrosis). The most common symptoms
are mild jaundice, fluid collection in the tissues, mental confusion, and vomiting of blood. If left untreated,
cirrhosis lead to liver failure and death.
Hemolytic disease of the newborn—Also known as
erythroblastosis neonatorum, this is a condition in
which a newborn’s red blood cells are destroyed by
antibodies that have crossed the placenta from the
mother’s blood. (Hemolytic disease begins in the
fetus, in whom the disease is called erythroblastosis
fetalis). Severe anemia caused by hemolytic disease
is treated in the same way as other anemias, but
when jaundice appears due to increased bilirubin,
the jaundice is treated by exposing the infant to
bright lights. In severe cases, exchange transfusion
is required or brain damage may result.
Hepatitis—An inflammation of the liver, with
accompanying liver cell damage or cell death,
caused most frequently by viral infection, but also
by certain drugs, chemicals, or poisons. May be
either acute (of limited duration) or chronic



AST: High levels may indicate liver cell damage,
hepatitis, heart attack, heart failure, or gall stones.



ALP: Elevated levels occur in diseases that impair
bile formation (cholestasis). ALP may also be elevated in many other liver disorders, as well as some
lung cancers (bronchogenic carcinoma) and
Hodgkin’s lymphoma. However, elevated ALP levels
may also occur in otherwise healthy people, especially among older people.

GGT: Increased levels are diagnostic of hepatitis,
cirrhosis, liver tumor or metastasis, as well as injury
from drugs toxic to the liver. Although the causes are
unclear, GGT levels may increase with alcohol ingestion, heart attack, pancreatitis, infectious mononucleosis, and Reye’s syndrome.
Bilirubin: Increased indirect or total bilirubin
levels can indicate various serious anemias, including
hemolytic disease of the newborn and transfusion reaction. Increased direct bilirubin levels can be diagnostic
of bile duct obstruction, gallstones, cirrhosis, or hepatitis. It is important to note that if total bilirubin levels
in the newborn reach or exceed critical levels,
exchange transfusion is necessary to avoid kernicterus,
a condition that causes brain damage.
GALE ENCYCLOPEDIA OF MEDICINE

(continuing). Symptoms include jaundice, nausea,
vomiting, loss of appetite, tenderness in the right
upper abdomen, aching muscles, and joint pain. In
severe cases, liver failure may result.
Hepatic encephalopathy—Also called liver encephalopathy or hepatic coma, this is a disorder in
which brain function deteriorates because toxic
substances, which would normally be removed by
the liver, accumulate in the bloodstream due to
liver damage or disease. Early symptoms include
subtle changes in logical thinking, personality and
behavior. As the disorder progresses, signs of drowsiness and confusion increase until eventually the
patient loses consciousness and lapses into coma.
Reye’s syndrome—A rare disorder characterized by
brain and liver damage following an upper respiratory tract infection, chickenpox, or influenza,
almost entirely confined to children under age
15, and often related to aspirin ingestion for a
viral infection. Symptoms include uncontrollable
vomiting, often with lethargy, memory loss, disorientation, or delirium. Swelling of the brain may
cause seizures, coma, and in severe cases, death.

Ammonia: Increased levels are seen in primary
liver cell disease, Reye’s syndrome, severe heart failure, hemolytic disease of the newborn, and hepatic
encephalopathy.
PT: Elevated in acute liver injury, vitamin K deficiencies, and disorders with impair the absorption of
vitamin K, including cholestasis.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Liver nuclear medicine scan
Definition
A liver scan is a diagnostic procedure to evaluate
the liver for suspected disease. A radioactive substance
2249

Liver nuclear medicine scan

KEY TERMS

Liver nuclear medicine scan

which concentrates in the liver is injected intravenously and the image of its distribution in the body is
analyzed to diagnose certain abnormalities.

Purpose
In the past, liver scans were used to evaluate the
liver in a wide variety of situations. It was considered
a useful study to detect abnormalities, but was often
not able to establish a specific diagnosis. In the
1990s, radionuclide imaging of the liver (use of a
radioactive form of cobalt or iodine) evolved into a
more specialized study, used to identify individual
diseases or conditions. This is accomplished by
using different radioisotopes precisely designed to
further evaluate a particular case. Isotopes are different forms of the same substance, such as radioactive iodine, that are injected into the body. This
allows the physician to trace the process of the substance throughout the part of the body that is being
tested for disease.
A liver scan is usually ordered after blood studies
and other imaging procedures have shown a liver
abnormality. It is most often used to further evaluate
masses or tumors. These may be benign growths in
the liver, or cancer which has developed in the
liver or has spread (or metastasized) from another
organ.
A liver scan may also be helpful in diagnosing
specific disorders, by detecting features which are
characteristic of a disorder, such as cirrhosis of the
liver. This study may also be part of the battery of
tests used to evaluate potential candidates for liver
transplant.

Precautions
Women who are pregnant or breast feeding
should not have this test.

Description
This test can be performed in an outpatient setting
or a hospital x-ray department. The patient usually lies
down while a radioactive substance (radioactive isotope) which accumulates in the liver is injected through
a vein in the arm. Scanning times may vary, depending
on the specific radioisotope used. It most often begins
within minutes after injection. The radionuclide scanner, sometimes called a gamma camera or scintillation
camera, is positioned above the upper abdomen and
may lightly touch the patient. It is important for the
patient to lie quietly. Position changes and brief periods
2250

KEY TERMS
Radioisotope—A radioactive, or radiation-emitting
form of an element.
Radionuclide—A substance which emits radiation
that can be detected by a scanner as the substance
disintegrates.

of breath holding may be required. The test usually
takes approximately one hour.
A specialized liver scan used to assess blood flow
is frequently used. It may be referred to as a radionuclide blood pool or volume study, a labeled red cell
scintigram, or some combination of these terms. Other
studies may be named for the radioisotope used. This
test may also be called a liver-spleen scan.

Preparation
No physical preparation is required. A liver scan
should be performed before doing any study that uses
iodinated or barium-containing contrast agents, to
prevent inaccurate results.
The patients should understand that there is no
danger of radioactive exposure to themselves or
others. Only small amounts of radionuclide are used.
The total amount of radiation absorbed is often less
than the dose received from ordinary x rays. The
scanner does not emit any radiation, but detects and
records it from the patient.

Aftercare
No special precautions are needed.

Normal results
A normal scan will show a liver of normal size,
shape, and position.

Abnormal results
An abnormal liver scan may result from a mass.
Depending on the radioisotope and technique used,
the scan may identify particular types of tumors or
certain cancers. Too much radioisotope in the spleen
and bones, compared to the liver, can indicate potential hypertension or cirrhosis. Liver diseases such as
cirrhosis or hepatitis may also cause an abnormal
scan, but are rarely diagnosed from the information
revealed by this study alone.
GALE ENCYCLOPEDIA OF MEDICINE

Liver transplantation

Resources
National Transplant Waiting List By Organ Type (June 2000)

PERIODICALS

Drane, Walter E. ‘‘Scintigraphic Techniques for Hepatic
Imaging.’’ Radiologic Clinics of North America 36
(March 1998): 309-318.

Organ Needed
Kidney
Liver
Heart
Lung
Kidney-Pancreas
Pancreas
Heart-Lung
Intestine

Ellen S. Weber, MSN

Number Waiting
48,349
15,987
4,139
3,695
2,437
942
212
137

Liver transplantation
Definition


Liver transplantation is a surgery that removes a
diseased liver and replace it with a healthy donor liver.

Purpose
The liver is the body’s principle chemical factory.
It receives all nutrients, drugs, and toxins absorbed
from the intestines and performs the final stages of
digestion, converting food into energy and replacement parts for the body. The liver also filters the
blood of all waste products, removes and detoxifies
poisons and excretes many of these into the bile. It
processes other chemicals for excretion by the kidneys.
The liver is also an energy storage organ, changing
food energy to a chemical called glycogen that can be
rapidly converted to fuel.
As the liver fails, all of its functions diminish.
Nutrition suffers, toxins build up, and waste products
accumulate. Scar tissue builds up on the liver if disease
is of long duration. As the liver scars, blood flow is
progressively restricted in the portal vein, which carries blood from the stomach and abdominal organs to
the liver. The resulting high blood pressure (hypertension) causes swelling of and bleeding from the blood
vessels of the esophagus. Severe jaundice, fluid accumulation in the abdomen (ascites), and deterioration
of mental function, due to the build-up of toxins in the
blood (liver encephalopathy), eventually occur, leading
to death.

The remainder comes from selected cancers, other
uncommon diseases, and a situation called fulminant
liver failure.

Fulminant liver failure most commonly happens
during acute viral hepatitis, but it is also the result of
mushroom poisoning by Amanita phalloides and toxic
reactions to some medicines, like an overdose of acetaminophen. This is a special category of candidates for
liver transplant because of the speed of their disease
and the immediate need of treatment.
The first human liver transplant was performed in
1963, and since then, thousands of liver transplants are
done every year. Since the introduction of of cyclosporine (a drug that suppresses the immune response
that rejects the donor organ), success rates for liver
transplantation have reached 85%.

Precautions
Patients with advanced heart and lung disease,
who are HIV positive, and who abuse drugs and alcohol are poor candidates for liver tranplantation. Their
ability to survive the surgery and the difficult recovery
period, as well as their longterm prognosis, is hindered
by their conditions.

Description
There are three types of liver transplantation
methods. They include:

Among the many causes of liver failure that bring
patients to transplant surgery are:



Orthotopic transplantation is the replacement of a
whole diseased liver with a healthy donor liver.



Progressive hepatitis (mostly due to virus infection)
accounts for more than a third.





Alcohol damage brings in about 20%

Heterotopic transplantation is the addition of a
donor liver at another site, while the diseased liver
is left intact.



Scarring or abnormality of the biliary system
accounts for roughly another 20%.



Reduced-size liver transplantation is the replacement
of a whole diseased liver with a portion of a healthy

GALE ENCYCLOPEDIA OF MEDICINE

2251

Liver transplantation

body for 10-20 hours by flushing it with cooled solutions of special chemicals and nutrients, so it can be
transported across the country.

Preparation

The diseased liver of a patient ready for transplantation.
(Custom Medical Stock Photo. Reproduced by permission.)

donor liver. Reduced-size liver transplants are most
often performed on children.
When an orthotopic transplantation is performed, a segment of the inferior vena cava attached
to the liver is taken from the donor as well. The same
parts are removed from the recipient and replaced by
connecting the inferior vena cava, the hepatic artery,
the portal vein and the bile ducts.
When there is a possibility that the afflicted liver
may recover, a heterotopic tranplantation is performed. The donor liver is placed in a different site,
but it still has to have the same connections. It is
usually attached very near the original liver, and if
the original liver recovers, the donor shrivels away. If
the original liver does not recover, it will shrivel, leaving the donor in place.
Reduced-size liver transplantation tranplants part
of a donor liver into a patient. It is possible to divide
the liver into eight pieces, each supplied by a different
set of blood vessels. Two of these pieces have been
enough to save a patient in liver failure, especially if
the patient is a child. It is therefore possible to transplant one liver into at least two patients and to transplant part of a liver from a living donor and have both
donor and recipient survive. Liver tissue grows to
accommodate its job so long as there is initially
enough of the organ to use. Patients have survived
with only 15-20% of their original liver, provided
that 15-20% was healthy.
Availability of organs for transplant is a current
crisis in the transplantation business. In October 1997,
a national distribution system was established that
gives priority to the sickest patients closest in location
to the donor liver, but makes livers available nationally. It is now possible to preserve a liver out of the
2252

Before transplantation takes place, the patient is
first determined to be a good candidate for transplantation by going through rigorous medical examination. A suitable candidate boosts their nutritional
intake in order to ensure that they are as healthy as
possible before surgery. Drugs are administered that
will decrease rejection after surgery. Consultation with
the patient, as well as any family, is conducted to
explain the surgery and its complications.
Psychological counciling is recommended.

Aftercare
In order to prevent organ rejection, immunosuppressive drugs will be taken. Hospitalization ranges
from four weeks to five months, depending on the
rate of recovery.
Successfully receiving a transplanted liver is only
the beginning of a life-long process. Patients with
transplanted livers have to stay on immunosuppressant
drugs for the rest of their lives to prevent organ rejection. Although many can reduce the dosage after the
initial few months, virtually none can discontinue
drugs altogether. Prednisone, azathioprine, and tacrolimus are often combined with cyclosporine for better
results. Newer immunosuppressive agents are coming
that promise even better results. In spite of immunosuppressants, rejection occurs most of the time and
requires additional medication. In some cases it cannot be reversed, and retransplantation becomes
necessary.

Risks
Early failure of the transplant occurs once in four
surgeries and has to be repeated. Some transplants
never work, some succumb to infection, and some
suffer immune rejection. Primary failure is apparent
within one or two days. Infections happen in half the
patients and often appear during the first week.
Rejection usually starts at the end of the first week.
The surgery itself may need revision because of narrowing, leaking, or blood clots at the connections.
There are potential social and economic problems,
psychological problems, and a vast array of possible
medical and surgical complications. Close medical surveillance must continue for the rest of the patient’s life.
GALE ENCYCLOPEDIA OF MEDICINE

Loaiasis see Filariasis

Acetaminophen—A common pain reliever (Tylenol).

Lobectomy see Lung surgery

Antigen—Any chemical that provokes an immune
response.

Lobotomy see Psychosurgery

Bile ducts—Tubes carrying bile from the liver to the
intestines.
Biliary system—The tree of tubes that carries bile.
Hepatic artery—The blood vessel supplying arterial blood to the liver.

Local anesthetic see Anesthesia, local
Localized scratch dermatitis see Lichen
simplex chronicus
Lockjaw see Tetanus

Inferior vena cava—The biggest vein in the body,
returning blood to the heart from the lower half of
the body.

Loperamide see Antidiarrheal drugs

Leukemia—A cancer of the white blood cells.
Lymphoma—A cancer of lymphatic tissue.

Lou Gehrig’s disease see Amyotrophic
lateral sclerosis

Portal vein—The blood vessel carrying venous
blood from the abdominal organs to the liver.

Low back pain

Ller-Christi see Histiocytosis X

KEY TERMS

Loratadine see Antihistamines

Louis-Bar syndrome see Ataxiatelangiectasia
Low potassium blood level see Hypokalemia

Infections are a constant risk while on immunosuppressive agents, because the immune system is supposed to
prevent them. A way has not yet been devised to control
rejection without hampering immune defenses against
infections. Not only do ordinary infections pose a threat,
but because of the impaired immunity, transplant
patients are susceptible to the same ‘‘opportunistic’’
infections that threaten AIDS patients–pneumocystis
pneumonia, herpes and cytomegalovirus infections,
fungi, and a host of bacteria.
Immunosuppression also hinders the body’s ability
to resist cancer. All the drugs used to prevent rejection
increase the risk of leukemias and lymphomas.
There is also a risk of the original disease returning. Hepatitis virus still inhabits the patient, as does
the urge to drink alcohol. Newer antiviral drugs hold
out promise for dealing with hepatitis, and Alcoholics
Anonymous (AA) is the most effective treatment
known for alcoholism.
Drug reactions are also a continuing threat. Every
drug used to suppress the immune system has potential problems.

Low back pain
Definition
Low back pain is a common musculoskeletal
symptom that may be either acute or chronic. It may
be caused by a variety of diseases and disorders that
affect the lumbar spine. Low back pain is often accompanied by sciatica, which is pain that involves the
sciatic nerve and is felt in the lower back, the buttocks,
and the backs of the thighs.

Description
Low back pain is a symptom that affects 80% of
the general United States population at some point in
life with sufficient severity to cause absence from
work. It is the second most common reason for visits
to primary care doctors, and is estimated to cost the
American economy $75 billion every year.
Low back pain may be experienced in several
different ways:

Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.

J. Ricker Polsdorfer, MD
GALE ENCYCLOPEDIA OF MEDICINE



Localized. In localized pain the patient will feel soreness or discomfort when the doctor palpates, or
presses on, a specific surface area of the lower back.



Diffuse. Diffuse pain is spread over a larger area and
comes from deep tissue layers.
2253

Low back pain



Radicular. The pain is caused by irritation of a nerve
root. Sciatica is an example of radicular pain.



Referred. The pain is perceived in the lower back but
is caused by inflammation elsewhere– often in the
kidneys or lower abdomen.

Causes and Symptoms
Acute pain
Acute pain in the lower back that does not extend
to the leg is most commonly caused by a sprain or
muscle tear, usually occurring within 24 hours of
heavy lifting or overuse of the back muscles. The
pain is usually localized, and there may be muscle
spasms or soreness when the doctor touches the area.
The patient usually feels better when resting.
Chronic pain
Chronic low back pain has several different possible causes:
MECHANICAL. Chronic strain on the muscles of the
lower back may be caused by obesity; pregnancy; or jobrelated stooping, bending, or other stressful postures.
MALIGNANCY. Low back pain at night that is not
relieved by lying down may be caused by a tumor in
the cauda equina (the roots of the spinal nerves controlling sensation in and movement of the legs), or a
cancer that has spread to the spine from the prostate,
breasts, or lungs. The risk factors for the spread of
cancer to the lower back include a history of smoking,
sudden weight loss, and age over 50.
ANKYLOSING SPONDYLITIS. Ankylosing spondylitis

is a form of arthritis that causes chronic pain in the
lower back. The pain is made worse by sitting or lying
down and improves when the patient gets up. It is
most commonly seen in males between 16 and 35.
Ankylosing spondylitis is often confused with
mechanical back pain in its early stages.
HERNIATED SPINAL DISK. Disk herniation is a dis-

order in which a spinal disk begins to bulge outward
between the vertebrae. Herniated or ruptured disks are
a common cause of chronic low back pain in adults.
PSYCHOGENIC. Back pain that is out of proportion to a minor injury, or that is unusually prolonged,
may be associated with a somatoform disorder or
other psychiatric disturbance.

Low back pain with leg involvement
Low back pain that radiates down the leg usually
indicates involvement of the sciatic nerve. The nerve
2254

can be pinched or irritated by herniated disks, tumors
of the cauda equina, abscesses in the space between the
spinal cord and its covering, spinal stenosis, and compression fractures. Some patients experience numbness
or weakness of the legs as well as pain.

Diagnosis
The diagnosis of low back pain can be complicated. Most cases are initially evaluated by primary
care physicians rather than by specialists.
Initial workup
PATIENT HISTORY. The doctor will ask the patient
specific questions about the location of the pain, its
characteristics, its onset, and the body positions or
activities that make it better or worse. If the doctor
suspects that the pain is referred from other organs, he
or she will ask about a history of diabetes, peptic
ulcers, kidney stones, urinary tract infections, or
heart murmurs.
PHYSICAL EXAMINATION. The doctor will examine
the patient’s back and hips to check for conditions that
require surgery or emergency treatment. The examination includes several tests that involve moving the
patient’s legs in specific positions to test for nerve
root irritation or disk herniation. The flexibility of
the lumbar vertebrae may be measured to rule out
ankylosing spondylitis.

Imaging studies
Imaging studies are not usually performed on
patients whose history and physical examination suggest routine muscle strain or overuse. X rays are
ordered for patients whose symptoms suggest cancer,
infection, inflammation, pelvic or abdominal disease,
or bone fractures. MRIs are usually ordered only for
patients with certain types of masses or tumors.
It is important to know that the appearance of
some abnormalities on imaging studies of the lower
back does not necessarily indicate that they cause the
pain. Many patients have minor deformities that do not
create symptoms. The doctor must compare the results
of imaging studies very carefully with information from
the patient’s history and physical examination.

Treatment
All forms of treatment of low back pain are aimed
either at symptom relief or to prevent interference with
the processes of healing. None of these methods
appear to speed up healing.
GALE ENCYCLOPEDIA OF MEDICINE

Physical therapy for chronic low back pain
usually includes regular exercise for fitness and flexibility, and massage or application of heat if necessary.
Lifestyle modifications include giving up smoking, weight reduction (if necessary), and evaluation
of the patient’s occupation or other customary
activities.
Patients with herniated disks are treated surgically
if the pain does not respond to medication.
A
B

Psychotherapy is recommended for patients
whose back pain is associated with a somatoform,
anxiety, or depressive disorder.

C

E

Patients with chronic low back pain sometimesbenefit from pain management techniques, including
biofeedback, acupuncture, and chiropractic manipulation of the spine.

D

Sites of low back pain. Pain anywhere along the spine (A) can
be caused by osteoarthritis. Pain along one or the other side
of the spine may be (B) a kidney infection. Trauma to back
muscles, joints, or disks (C) causes low back pain. Damage to
the coccyx (D) can occur during a fall. Sciatica (E) can
cause pain to run down from the back and buttocks area
down a leg. (Illustration by Electronic Illustrators Group.)

Acute pain
Acute back pain is treated with nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen,
muscle relaxants, or aspirin. Applications of heat or
cold compresses are also helpful to most patients. If
the patient has not experienced some improvement
after several weeks of treatment, the doctor will reinvestigate the cause of the pain.
Chronic pain
Patients with chronic back pain are treated witha
combination of medications, physical therapy, andoccupational or lifestyle modification. The medicationsgiven
GALE ENCYCLOPEDIA OF MEDICINE

Low back pain with leg involvement
Treatment of sciatica and other disorders that
involve the legs may include NSAIDs. Patients with
long-standing sciatica or spinal stenosis that do not
respond to NSAIDs are treated surgically. Although
some doctors use cortisone injections to relieve the
pain, this form of treatment is still debated.

Alternative treatment
A thorough differential diagnosis is important
before any treatment is considered. There are times
when alternative therapies are the most beneficial, and
other times when more invasive treatments are needed.
Chiropractic
Chiropractic treats patients by manipulating or
adjusting sections of the spine. It is one of the most
popular forms of alternative treatment in the United
States for relief of back pain caused by straining or
lifting injuries. Some osteopathic physicians, physical
therapists, and naturopathic physicians also use spinal
manipulation to treat patients with low back pain.
Traditional Chinese medicine
Practitioners of traditional Chinese medicine treat
low back pain with acupuncture, tui na (push-and-rub)
massage, and the application of herbal poultices.
2255

Low back pain

are usually NSAIDs, although patients withhypertension, kidney problems, or stomach ulcers should not
take these drugs. Patients who take NSAIDs for longer
than six weeks should be monitored periodically for
complications.

Lower esophageal ring

Body work and yoga

KEY TERMS
Ankylosing spondylitis—A type of arthritis that
causes gradual loss of flexibility in the spinal column. It occurs most commonly in males between
16 and 35.
Cauda equina—The roots of the spinal nerves controlling movement and sensation in the legs. These
nerve roots are located in the lower spine and
resemble a horse’s tail (cauda equina in Latin).
Chiropractic—A method of treatment based on the
interactions of the spine and the nervous system.
Chiropractors adjust or manipulate segments of the
patient’s spinal column in order to relieve pain.
Lumbar spine—The segment of the human spine
above the pelvis that is involved in low back pain.
There are five vertebrae, or bones, in the lumbar
spine.
Radicular—Pain that is caused by the root of a
nerve.
Referred pain—Pain that is experienced in one part
of the body but originates in another organ or area.
The pain is referred because the nerves that supply
the damaged organ enter the spine in the same
segment as the nerves that supply the area where
the pain is felt.
Sciatica—Pain caused by irritation of the sciatic
nerve. Sciatica is felt in the lower back, the buttocks, and the backs of the upper legs.
Spinal stenosis—A form of sciatica that is caused by
a narrowing of the spinal canal in the lumbar vertebrae. The narrowing puts pressure on the roots of
the sciatic nerve.

Herbal medicine
Herbal medicine can utilize a variety of antispasmodic herbs in combination to help relieve low back
pain due to spasm. Lobelia (Lobelia inflata) and myrrh
(Commiphora molmol) are two examples of antispasmodic herbs.

Massage and the numerous other body work techniques can be very effective in treating low back pain.
Yoga, practiced regularly and done properly, can be most
useful in preventing future episodes of low back pain.

Prognosis
The prognosis for most patients with acute low
back pain is excellent. About 80% of patients recover
completely in 4-6 weeks. The prognosis for recovery
from chronic pain depends on the underlying cause.

Prevention
Low back pain due to muscle strain can be prevented by lifestyle choices, including regular physical
exercise and weight control, avoiding smoking, and
learning the proper techniques for lifting and moving
heavy objects. Exercises designed to strengthen the
muscles of the lower back, and chairs or car seats
with lumbar supports are also recommended.
Resources
BOOKS

Hellman, David B. ‘‘Arthritis & Musculoskeletal
Disorders.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al.,
37th ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Low blood magnesium see Magnesium
imbalance
Low blood phosphate level see Phosphorus
imbalance
Low blood pressure see Orthostatic
hypotension; Hypotension
Low blood sugar see Hypoglycemia
Low calcium blood level see Hypocalcemia
Low sodium blood level see Hyponatremia

Homeopathy
Homeopathic treatment for acute back pain consists of applications of Arnica oil to the sore area or
oral doses of Arnica or Rhus toxicodendron. Bellis
perennis is recommended for deep muscle injuries.
Other remedies may be recommended based on the
symptoms presented by the patient.
2256

Lower esophageal ring
Definition
Lower esophageal ring is a condition in which
there is a ring of tissue inside the lower part of the
GALE ENCYCLOPEDIA OF MEDICINE

Description
Lower esophageal ring (also called Schatzki’s ring
and B-ring) affects about 10-14% of the population.
Normally, the lower part of the esophagus, near where
the esophagus meets the stomach, has an inside diameter of 1.5-2 inches. The diameter of this part of the
esophagus is less when lower esophageal ring is present, and diameters as small as one-eighth inch have
been seen. When the inside diameter is less than about
three-fourths of an inch, intermittent difficulty with
swallowing can result. About 96% of people with
lower esophageal ring have no symptoms.

Causes and symptoms
Causes
Lower esophageal ring seems to result from
infoldings of tissue near the bottom of the esophagus,
but the underlying cause is unknown. Although some
specialists speculate they are due to a congenital
defect, most people do not develop symptoms until
they reach their forties or later. Although lower esophageal ring is generally associated with hiatal hernia,
and sometimes with heartburn, the cause/effect relationship is unclear.
Symptoms
Intermittent difficulty swallowing solid food is the
primary symptom of this condition. The degree of
difficulty in swallowing is directly related to the degree
the esophagus is narrowed. Certain foods, especially
tough or fibrous foods like meat, are more likely to
cause swallowing difficulties.

Diagnosis
Gastroenterologists and internists are best
equipped to diagnose and treat lower esophageal
ring. The diagnosis is based on the patient’s history
of swallowing difficulties and a barium x ray of the
upper gastrointestinal tract. For a barium x ray, the
patient swallows a liquid containing barium, a substance that is opaque to x rays. Subsequent x-ray
photography reveals the shape of the esophagus and
any narrow regions present.
The presence of a lower esophageal ring can also
be shown with a test called an esophagoscopy. This
GALE ENCYCLOPEDIA OF MEDICINE

procedure visualizes the inside of the esophagus with
an inserted, thin, flexible tube. However, this test is
less sensitive for lower esophageal ring and costs about
five times as much as barium x ray. However, if the
findings of a barium x ray are not definitive, esophagoscopy should be done. Biopsies can then be done on
questionable areas.

Treatment
Dietary change
Swallowing difficulties due to lower esophageal
ring can often be relieved by chewing food more thoroughly. Soft foods and liquids may also be
recommended.
Dilation
Lower esophageal rings can be corrected by passing a bougie (a cylindrical, mercury-filled dilator)
through the esophagus. This procedure, called bougienage, is effective most of the time, but may need to be
repeated every few years. Complications and adverse
reactions are extremely rare.
Surgery
If bougienage is unsuccessful, lower esophageal
ring tissue can be surgically removed.

Prognosis
The probability of a favorable outcome is high.
Swallowing difficulties can be alleviated in almost
every case, and the rate of complications from bougienage or surgery is less than 1%.

Prevention
Since the cause of lower esophageal ring is not
known, there are no definitive preventive measures.
Nevertheless, anyone with lower esophageal ring who
also suffers from heartburn would be wise to prevent
or treat the heartburn. It is possible that the stomach
acid in the esophagus associated with heartburn contributes to esophageal ring.
Resources
ORGANIZATIONS

The American College of Gastroenterology (ACG). P.O.
Box 3099, Alexandria, VA 22302. (800) 432-2876.
<http://www.healthtouch.com>.
American Gastroenterological Association (AGA). 7910
Woodmont Ave., 7th Floor, Bethesda, MD 20814.
2257

Lower esophageal ring

esophagus (the tube connecting the throat with the
stomach). This tissue causes narrowing and partial
blockage of the esophagus. Lower esophageal ring
can also refer to the ring itself.

Lumpectomy

KEY TERMS
Bougie—A mercury-filled dilator in the shape of a
cylinder or tapered cylinder. Bougies come in a
range of different sizes.
Bougienage—The procedure of dilating tubal
organs, like the esophagus, with a bougie or
bougies.
Congenital—Existing at birth.
Dysphagia—Difficulty swallowing.
Esophagoscopy (also esophagoendoscopy)—
Examination of the inside of the esophagus using a
flexible tube that transmits video images.
Esophagus —The tube connecting the throat to the
stomach, which is about ten inches long in adults. It
is coated with mucus and surrounded by muscles,
and pushes food to the stomach by sequential
waves of contraction. It functions to transport food
from the throat to the stomach and to keep the
contents of the stomach in the stomach.
Heartburn—A burning sensation in the chest that
can extend to the neck, throat, and face, caused by
the movement of stomach acid into the esophagus.
Hiatal hernia—A condition where part of the stomach extends through the diaphragm into the chest
cavity.

(310) 654-2055. <aga001@aol.com> <http://
www.gastro.org/index.html>.
American Society for Gastrointestinal Endoscopy.
13 Elm St., Manchester, MA 01944. (508) 526-8330.
<http://www.asge.org/doc/201>.
National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/digest/
nddic.htm>.

Lorraine Lica, PhD

Lower GI exam see Barium enema
LSD see Lysergic acid diethylamide
Lues see Syphilis
Lumbar puncture see Cerebrospinal fluid
(CSF) analysis
Lumbar stenosis see Spinal stenosis
Lumbosacral radiculopathy see Sciatica
2258

Lumpectomy
Definition
A lumpectomy is a type of surgery used to treat
breast cancer. It is considered ‘‘breast-conserving’’
surgery because in a lumpectomy, only the malignant
tumor and a surrounding margin of normal breast
tissue are removed. Lymph nodes in the armpit (axilla)
also may be removed. This procedure is called lymph
node dissection.

Purpose
Lumpectomy is a surgical treatment for newly
diagnosed breast cancer. It is estimated that at least
50% of women with breast cancer are good candidates
for this procedure. The location, size, and type of tumor
are of primary importance when considering breast
cancer surgery options. The size of the breast is another
factor the surgeon considers when recommending surgery. The patient’s psychological outlook, as well as her
lifestyle and preferences, should also be taken into
account when treatment decisions are made.
The extent and severity of a cancer is evaluated or
‘‘staged’’ according to a fairly complex system.
Staging considers the size of the tumor and whether
the cancer has spread to other areas, such as the chest
wall and the lymph nodes, and/or to distant parts of
the body. Women with early stage breast cancers
usually are better candidates for lumpectomy. In
most cases, a course of radiation therapy after surgery
is part of the treatment. Chemotherapy or antiestrogens also may be prescribed.
Many studies have compared the survival rates of
women who have had removal of a breast (mastectomy)
with those who have undergone lumpectomy and radiation therapy. The data demonstrate that for women
with comparable stages of breast cancer, survival rates
are similar between the two groups, but the risk of the
cancer recurring in the breast is slightly higher with
lumpectomy. A 2003 study confirmed that younger
women who have lumpectomies have a higher risk of
tumor recurrence than those who have mastectomies.
In some instances, women with later stage breast
cancer may be able to have lumpectomy. Chemotherapy
may be administered before surgery to decrease tumor
size and the chance of spread in selected cases.

Precautions
A number of factors may prevent or prohibit a
breast cancer patient from having a lumpectomy. The
GALE ENCYCLOPEDIA OF MEDICINE

Certain medical or physical circumstances also
may eliminate lumpectomy as a treatment option.
Sometimes lumpectomy may be attempted, but the
surgeon is unable to remove the tumor with a sufficient amount of normal tissue surrounding it. This
may be termed ‘‘persistently positive margins,’’ or
‘‘lack of clear margins,’’ referring to the margin of
unaffected tissue around the tumor. Lumpectomy is
not used for women who have had a previous lumpectomy and have a recurrence of the breast cancer.
The need for radiation therapy after lumpectomy
makes this surgery medically unacceptable for some
women. For instance, radiation therapy cannot be
administered to pregnant women because it may injure
the fetus. If, however, delivery would be completed
prior to the need for radiation, pregnant women may
undergo lumpectomy. Women with collagen vascular
disease, such as lupus erythematosus or scleroderma,
would experience scarring and damage to their connective tissue if exposed to radiation treatments. A
woman who has already had therapeutic radiation to
the chest area for other reasons cannot have additional
exposure for breast cancer therapy.
Some women may choose not to have a lumpectomy for other reasons. They may strongly fear a recurrence of breast cancer, and may consider a lumpectomy
too risky. Others feel uncomfortable living with a
cancerous breast and experience more peace of mind
with the entire breast removed.
The need for radiation therapy also may be a
barrier due to non-medical concerns. Some women
simply fear this type of treatment and choose more
extensive surgery so that radiation will not be
required. The commitment of time, usually five days
a week for six weeks, may not be acceptable for others.
This may be due to financial, personal, or job-related
constraints. Finally, in geographically isolated areas, a
course of radiation therapy may require lengthy travel, and perhaps unacceptable amounts of time away
from family and other responsibilities.

Description
Lumpectomy is an imprecise term. Any amount of
tissue, from 1% to 50% of the breast, may be removed
GALE ENCYCLOPEDIA OF MEDICINE

and called a lumpectomy. Breast conservation surgery
is a frequently-used synonym for lumpectomy. Partial
mastectomy, quadrantectomy, segmental excision,
wide excision, and tylectomy are other names for this
procedure.
A lumpectomy is frequently done in a hospital
setting (especially if lymph nodes are to be removed
at the same time), but specialized outpatient facilities
sometimes are preferred. The surgery is usually done
while the patient is under general anesthesia. Local
anesthetic with additional sedation may be used for
some patients. The tumor and surrounding margin of
tissue is removed and sent to the pathologist. The
surgical site is closed.
If axillary lymph nodes were not removed in a
prior biopsy, a second incision is made in the armpit.
The fat pad that contains lymph nodes is removed
from this area and also is sent to the pathologist for
analysis. This portion of the procedure is called an
axillary lymph node dissection; it is critical for determining the stage of the cancer. Typically, 10 to 15
nodes are removed, but the number may vary.
Surgical drains may be left in place in either location
to prevent fluid accumulation. The surgery may last
from one to three hours.
The patient may stay in the hospital one or two
days, or return home the same day. This generally
depends on the extent of the surgery and the medical
condition of the patient, as well as physician and
patient preferences. A woman usually goes home
with a small bandage. The inner part of the surgical
site usually has dissolvable stitches. The skin may be
sutured or stitched; or the skin edges may be held
together with steristrips, which are special thin, clear
pieces of tape.

Preparation
Routine preoperative preparations, such as having nothing to eat or drink the night before surgery,
are typically ordered for a lumpectomy. Information
about expected outcomes and potential complications
also is part of preparation for lumpectomy, as it is for
any surgical procedure. It is especially important that
women know about sensations they might experience
after the operation, so the sensations are not misinterpreted as signs of further cancer or poor healing.
If the tumor cannot be felt (not palpable), a preoperative localization procedure is needed. A fine
wire, or other device is placed at the tumor site, using
x ray or ultrasound for guidance. This is usually done
in the radiology department of a hospital. The woman
2259

Lumpectomy

tumor itself may be too large or located in an area
where it would be difficult to remove with good cosmetic results. Sometimes several areas of cancer are
found in one breast, so the tumor cannot be removed
as a single lump. A cancer that has already attached
itself to nearby structures, such as the skin or the chest
wall, needs more extensive surgery.

Lumpectomy

is most often sitting up and awake, although some
sedation may be administered.

Aftercare
After a lumpectomy, patients are usually cautioned against lifting anything that weighs more than
five pounds for several days. Other activities may be
restricted (especially if the axillary lymph nodes were
removed) according to individual needs. Pain is often
enough to limit inappropriate motion. Women often
are instructed to wear a well-fitting support bra both
day and night for approximately one week after
surgery.
Pain is usually well controlled with prescribed
medication. If it is not, the patient should contact the
surgeon, as severe pain may be a sign of a complication
that needs medical attention. A return visit to the
surgeon normally is scheduled approximately 10 days
to two weeks after the operation. Studies have shown
that women improve their survival rates after lumpectomy if they stop smoking.
Radiation therapy is usually started as soon as
feasible after lumpectomy. Other additional treatments, such as chemotherapy or hormone therapy,
may also be prescribed. The timing of these is specific
to each individual patient.

Risks
The risks are similar to those associated with any
surgical procedure. Risks include bleeding, infection,
asymmetry, anesthesia reaction, or unexpected scarring. A lumpectomy also may cause loss of sensation
in the breast. The size and shape of the breast will be
affected by the operation. Fluid can accumulate in the
area where tissue was removed, requiring drainage.
If lymph node dissection is performed, there are
several potential complications. A woman may experience decreased feeling in the back of her armpit. She
also may experience other sensations, including numbness, tingling, or increased skin sensitivity. An inflammation of the arm vein, called phlebitis, can occur.
There may be injury to the nerves controlling arm
motion.
Approximately 2% to 10% of patients develop
lymphedema (swelling of the arm) after axillary
lymph node dissection. This swelling of the arm can
range from mild to severe. It can be treated with elastic
bandages and specialized physical therapy, but it is a
chronic condition, requiring continuing care.
Lymphedema can arise at any time, even years after
surgery.
2260

KEY TERMS
Lymph node—A small mass of tissue in the form of
a knot or protuberance. Lymph nodes are the primary sources of lymph fluid, which serve in the
body’s defense by removing toxic fluids and
bacteria.

A new technique often eliminates the need to
remove many axillary lymph nodes. Sentinel lymph
node mapping and biopsy is based on the idea that
the condition of the first lymph node in the network,
which drains the affected area, can predict whether the
cancer may have spread to the rest of the nodes. It is
thought that if this first, or sentinel, node is cancerfree, there is no need to look further. Many patients
with early-stage breast cancers may be spared the risks
and complications of axillary lymph node dissection as
the use of this approach continues to increase.

Normal results
When lumpectomy is performed, it is anticipated
that it will be the definitive surgical treatment for breast
cancer. Other forms of therapy, especially radiation, are
often prescribed as part of the total treatment plan. A
2003 study reported that radiation of the entire breast
produces better results than radiation of part of the
breast. The expected outcome after lumpectomy and
radiation is no recurrence of the breast cancer, however,
women who have had lumpectomies, particularly those
who were young at the time of treatment, should continue to see their physicians for regular breast cancer
check-ups, since the cancer can recur.

Abnormal results
An unforeseen outcome of lumpectomy may be
recurrence of the breast cancer, either locally or distally (in a part of the body far from the original site).
Recurrence may be discovered soon after lumpectomy
or years after the procedure. For this reason, it is
important for patients to be regularly and closely
monitored by their physicians. A 2003 report showed
that magnetic resonance imaging (MRI) is accurate in
detecting any cancer left in the breast after lumpectomy. Women should continue to have regular mammograms. While the scar tissue from lumpectomy and
radiation therapy can make mammograms less comfortable, a special cushion was approved by the U.S.
Food and Drug Administration in 2003 that reduces
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

Ford, Steve. ‘‘Lumpectomy Associated With Higher Longterm Risk of Recurrence than Mastectomy.’’ Practice
Nurse November 28, 2003: 50.
Jancin, Bruce. ‘‘Cushion Lessens Mammogram Pain After
Lumpectomy (Pain Decreased 54%).’’ OB GYN News
(February 15, 2003): 9 - 11.
‘‘MR Accurate in Detecting Residual Disease Following
Lumpectomy.’’ Women’s Health Weekly May 29,
2003:14.
Norton, Patrice G.W. ‘‘More Data Support Breast
Conservation Over Mastectomy (For Phase I or II
Cancer).’’ Family Practice News January 15, 2003: 31.
‘‘Smoking Decreases Survival of Patients Treated with
Lumpectomy and Radiation.’’ Cancer Weekly
November 11, 2003: 36.
‘‘Study: Whole-breast Irradiation After Lumpectomy Has
Clear Long-term Benefits.’’ Cancer Weekly November
11, 2003: 39.

Ellen S. Weber, MSN
Teresa G. Odle

Lumpy breasts see Fibrocystic condition of
the breast
Lumpy jaw see Actinomycosis

Lung abscess
Definition
Lung abscess is an acute or chronic infection of
the lung, marked by a localized collection of pus,
inflammation, and destruction of tissue.

Description
Lung abscess is the end result of a number of
different disease processes ranging from fungal and
bacterial infections to cancer. It can affect anyone at
any age. Patients who are most vulnerable include
those weakened by cancer and other chronic diseases;
patients with a history of substance abuse, diabetes,
epilepsy, or poor dental hygiene; patients who have
recently had operations under anesthesia; and stroke
patients. In children, the most vulnerable patients are
those with weakened immune systems, malnutrition, or
blunt injuries to the chest.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The immediate cause of most lung abscesses is
infection caused by bacteria. About 65% of these infections are produced by anaerobes, which are bacteria
that do not need air or oxygen to live. The remaining
cases are caused by a mixture of anaerobic and aerobic
(air breathing) bacteria. When the bacteria arrive in the
lung, they are engulfed or eaten by special cells called
phagocytes. The phagocytes release chemicals that contribute to inflammation and eventual necrosis, or death,
of a part of the lung tissue. There are several different
ways that bacteria can get into the lung.
Aspiration
Aspiration refers to the accidental inhalation of
material from the mouth or throat into the airway and
lungs. It is responsible for about 50% of cases of lung
abscess. The human mouth and gums contain large
numbers of anaerobic bacteria; patients with periodontal disease or poor oral hygiene have higher concentrations of these organisms. Aspiration is most likely
to occur in patients who are unconscious or semiconscious due to anesthesia, seizures, alcohol and
drug abuse, or stroke. Patients who have problems
swallowing or coughing, or who have nasogastric
tubes in place are also at risk of aspiration.
Bronchial obstruction
The bronchi are the two branches of the windpipe
that lead into the lungs. If they are blocked by tissue
swelling, cancerous tumors, or foreign objects, a lung
abscess may form from infection trapped behind the
blockage.
Spread of infection
About 20% of cases of pneumonia that cause the
death of lung tissue (necrotizing pneumonia) will
develop into lung abscess. Lung abscess can also be
caused by the spread of other infections from the liver,
abdominal cavity, or open chest wounds. Rarely,
AIDS patients can develop lung abscess from
Pneumocystis carinii and other organisms that take
advantage of a weakened immune system.
Lung abscess is usually slow to develop. It may
take about two weeks after aspiration or bronchial
obstruction for an abscess to produce noticeable
symptoms. The patient may be acutely ill for two
weeks to three months. In the beginning, the symptoms of lung abscess are difficult to distinguish from
those of severe pneumonia. Adults will usually have
moderate fever (101-102 8F/38-39 8C), chills, chest
2261

Lung abscess

discomfort in women who have had breast conserving
surgery.

Lung abscess

pain, and general weakness. Children may or may not
have chest pain, but usually suffer weight loss and high
fevers. As the illness progresses, about 75% of patients
will cough up foul or musty-smelling sputum; some
also cough up blood.
Lung abscess can lead to serious complications,
including emphysema, spread of the abscess to other
parts of the lung, hemorrhage, adult respiratory distress syndrome, rupture of the abscess, inflammation
of the membrane surrounding the heart, or chronic
inflammation of the lung.

Diagnosis
The diagnosis is made on the basis of the patient’s
medical history (especially recent operations under general anesthesia) and general health as well as imaging
studies. Smears and cultures taken from the patient’s
sputum are not usually very helpful because they will be
contaminated with bacteria from the mouth. The doctor will first use a bronchoscope (lighted tube inserted
into the windpipe) to rule out the possibility of lung
cancer. In some cases of serious infection, the doctor
can use a fiberoptic bronchoscope with a protected
specimen brush to take material directly from the
patient’s lungs, for identification of the organism.
This technique is time- consuming and expensive, and
requires the patient to be taken off antibiotics for
48 hours. It is usually used only to evaluate severely ill
patients with weakened immune systems.
In most cases, the doctor will use the results of a
chest x ray to help distinguish lung abscess from
empyema, cancer, tuberculosis, or cysts. In patients
with lung abscess, the x ray will show a thick-walled
unified clear space or cavity surrounded by solid tissue. There is often a visible air-fluid level. The doctor
may also order a CT scan of the chest, in order to have
a clearer picture of the exact location of the abscess.
Blood tests cannot be used to make a diagnosis of
lung abscess, but they can be useful in ruling out other
conditions. Patients with lung abscess usually have
abnormally high white blood cell counts (leukocytosis)
when their blood is tested, but this condition is not
unique to lung abscess.

Treatment
Lung abscess is treated with a combination of
antibiotic drugs, oxygen therapy, and surgery. The
antibiotics that are usually given for lung abscess are
penicillin G, penicillin V, and clindamycin. They are
given intravenously until the patient shows signs of
improvement, and then continued in oral form. The
2262

patient may need to take antibiotics for a month or
longer, until the chest x ray indicates that the abscess is
healing. Oxygen may be given to patients who are
having trouble breathing.
Surgical treatment
Most patients with lung abscess will not need
surgery. About 5% of patients–usually those who do
not respond to antibiotics or are coughing up large
amounts of blood (500 mL or more)–may have emergency surgery for removal of the diseased part of the
lung or for insertion of a tube to drain the abscess.
Antibiotic treatment is considered to have failed if
fever and other symptoms continue after 10-14 days
of treatment; if chest x rays indicate that the abscess is
not shrinking; or if the patient has pneumonia that is
spreading to other parts of the lung.
Supportive care
Because lung abscess is a serious condition,
patients need quiet and bed rest. Hospital care usually
includes increasing the patient’s fluid intake to loosen
up the secretions in the lungs, and physical therapy to
strengthen the patient’s breathing muscles.
Follow-up
Patients with lung abscess need careful follow-up
care after the acute infection subsides. Follow-up
usually includes a series of chest x rays to make sure
that the infection has cleared up. Treatment with antibiotics may continue for as long as four months, to
prevent recurrence.

Prognosis
About 95% of lung abscess patients can be treated
successfully with antibiotics alone. Patients who need
surgical treatment have a mortality rate of 10-15%.

Prevention
Some of the conditions that make people more
vulnerable to lung abscess concern long-term lifestyle
behaviors, such as substance abuse and lack of dental
care. Others, however, are connected with chronic illness and hospitalization. Aspiration can be prevented
with proper care of unconscious patients, which
includes suctioning of throat secretions and positioning patients to promote drainage. Patients who are
conscious can be given physical therapy to help them
cough up material in their lungs and airways. Patients
GALE ENCYCLOPEDIA OF MEDICINE

Abscess—An area of injured body tissue that fills
with pus, as in lung abscess.
Anaerobe—A type of bacterium that does not
require air or oxygen to live. Anaerobic bacteria
are frequent causes of lung abscess.
Aspiration—Inhalation of fluid or foreign bodies
into the airway or lungs. Aspiration often happens
after vomiting.
Bronchoscope—A lighted, flexible tube inserted
into the windpipe to view the bronchi or withdraw
fluid samples for testing. Bronchoscopy with a protected brush can be used in the diagnosis of lung
abscess in severely ill patients.
Bronchus—One of the two large tubes connecting
the windpipe and the lungs.
Leukocytosis—An increased level of white cells in
the blood. Leukocytosis is a common reaction to
infections, including lung abscess.
Necrotizing pneumonia—Pneumonia that causes
the death of lung tissue. It often precedes the development of lung abscess.
Sputum—The substance that is brought up from the
lungs and airway when a person coughs or spits. It
is usually a mixture of saliva and mucus, but may
contain blood or pus in patients with lung abscess
or other diseases of the lungs.

with weakened immune systems can be isolated from
patients with pneumonia or fungal infections.

under a microscope. Biopsy examinations are usually
performed by pathologists, who are doctors with special training in tissue abnormalities and other signs of
disease.

Purpose
Lung biopsies are useful, first of all, in confirming
a diagnosis of cancer, especially if malignant cells are
detected in the patient’s sputum. A lung biopsy may be
ordered to examine other abnormalities that appear
on chest x rays, such as lumps (nodules). It is also
helpful in diagnosing symptoms such as coughing up
bloody sputum, wheezing in the chest, or difficult
breathing. In addition to evaluating lung tumors and
their associated symptoms, lung biopsies can be used
in the diagnosis of lung infections, especially tuberculosis, drug reactions, and such chronic diseases of the
lung as sarcoidosis.
A lung biopsy can be used for treatment as well as
diagnosis. Bronchoscopy, which is a type of lung
biopsy performed with a long slender instrument
called a bronchoscope, can be used to clear a patient’s
air passages of secretions and to remove blockages
from the airways.

Precautions
As with any other biopsy, lung biopsies should not
be performed on patients who have problems with
blood clotting because of low platelet counts.
Platelets are small blood cells that play a role in the
blood clotting process. If the patient has a platelet
count lower than 50,000/cubic mm, he or she can be
given a platelet transfusion as a temporary relief measure, and a biopsy can then be performed.

Resources

Description

BOOKS

Stauffer, John L. ‘‘Lung.’’ In Current Medical Diagnosis
and Treatment, 1998, edited by Stephen McPhee, et al.,
37th ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Lung biopsy
Definition
Lung biopsy is a medical procedure performed to
obtain a small piece of lung tissue for examination
GALE ENCYCLOPEDIA OF MEDICINE

Overview
The lungs are a pair of cone-shaped organs that lie
in the chest cavity. An area known as the mediastinum
separates the right and the left lungs from each other.
The heart, the windpipe (trachea), the lymph nodes,
and the tube that brings the food to the stomach (the
esophagus) lie in this mediastinal cavity. Lung biopsies
may involve entering the mediastinum, as well as the
lungs themselves.
Types of lung biopsies
Lung biopsies can be performed using a variety of
techniques. A bronchoscopy is ordered if a patch that
looks suspicious on the x ray seems to be located deep
2263

Lung biopsy

KEY TERMS

Lung biopsy

in the chest. If the area lies close to the chest wall, a
needle biopsy is often done. If both these methods fail
to diagnose the problem, an open surgical biopsy may
be carried out. If there are indications that the lung
cancer has spread to the lymph nodes in the mediastinum, a mediastinoscopy is performed.
NEEDLE BIOPSY. When a needle biopsy is to be
done, the patient will be given a sedative about an
hour before the procedure, to help relaxation. The
patient sits in a chair with arms folded on a table in
front of him or her. X rays are then taken to identify
the location of the suspicious areas. Small metal markers are placed on the overlying skin to mark the
biopsy site. The skin is thoroughly cleansed with an
antiseptic solution, and a local anesthetic is injected to
numb the area.

The doctor then makes a small cut (incision)
about half an inch in length. The patient is asked to
take a deep breath and hold it while the doctor inserts
the special biopsy needle through the incision into the
lung. When enough tissue has been obtained, the needle is withdrawn. Pressure is applied at the biopsy site
and a sterile bandage is placed over the cut. The entire
procedure takes between 30 and 45 minutes.
The patient may feel a brief sharp pain or some
pressure as the biopsy needle is inserted. Most
patients, however, do not experience severe pain.
OPEN BIOPSY. Open biopsies are performed in a
hospital under general anesthesia. As with needle biopsies, patients are given sedatives before the procedure.
An intravenous line is placed in the arm to give medications or fluids as necessary. A hollow tube, called an
endotracheal tube, is passed through the throat, into
the airway leading to the lungs. It is used to convey the
general anesthetic.

have some pain or discomfort at the incision site,
which can be relieved by medication.
MEDIASTINOSCOPY. The preparation for a mediastinoscopy is similar to that for an open biopsy.
The patient is sedated and prepared for general
anesthesia. The neck and the chest will be cleansed
with an antiseptic solution.

After the patient has been put to sleep, an incision
about two or three inches long is made at the base of
the neck. A thin, hollow, lighted tube, called a mediastinoscope, is inserted through the cut into the space
between the right and the left lungs. The doctor examines the space thoroughly and removes any lymph
nodes or tissues that look abnormal. The mediastinoscope is then removed, and the incision stitched up and
bandaged. A mediastinoscopy takes about an hour.

Preparation
Before scheduling any lung biopsy, the doctor will
check to see if the patient is taking any prescription
medications, if he or she has any medication allergies,
and if there is a history of bleeding problems. Blood
tests may be performed before the procedure to check
for clotting problems and blood type, in case a transfusion becomes necessary.
If an open biopsy or a mediastinoscopy is being
performed, the patient will be asked to sign a consent
form. Since these procedures are done under general
anesthesia, the patient will be asked to refrain from
eating or drinking anything for at least 12 hours before
the biopsy.

Aftercare
Needle biopsy

Once the patient is under the influence of the
anesthesia, the surgeon makes an incision over the
lung area. Some lung tissue is removed and the cut
closed with stitches. The entire procedure usually
takes about an hour. A chest tube is sometimes placed
with one end inside the lung and the other end protruding through the closed incision. Chest tube placement is done to prevent the lungs from collapsing by
removing the air from the lungs. The tube is removed a
few days after the biopsy.

Following a needle biopsy, the patient is allowed
to rest comfortably. He or she will be checked by a
nurse at two-hour intervals. If there are no complications after four hours, the patient can go home.
Patients are advised to rest at home for a day or two
before resuming regular activities, and to avoid strenuous activities for a week after the biopsy.

A chest x ray is done following an open biopsy, to
check for lung collapse. The patient may experience
some grogginess for a few hours after the procedure.
He or she may also experience tiredness and muscle
aches for a day or two, because of the general anesthesia. The throat may be sore because of the placement
of the hollow endotracheal tube. The patient may also

After an open biopsy or a mediastinoscopy,
patients are taken to a recovery room for observation.
If no other complications develop, they are taken back
to the hospital room. Stitches are usually removed
after seven to 14 days.

2264

Open biopsy or mediastinoscopy

If the patient has extreme pain, light-headedness,
difficulty breathing, or develops a blue tinge to the
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Needle biopsy
Needle biopsy is a less risky procedure than an
open biopsy, because it does not involve general
anesthesia. Very rarely, the lung may collapse because
of air that leaks in through the hole made by the
biopsy needle. If the lung collapses, a tube will have
to be inserted into the chest to remove the air. Some
coughing up of blood occurs in 5% of needle biopsies.
Prolonged bleeding or infection may also occur,
although these are very rare.
Open biopsy
Possible complications of an open biopsy include
infection or lung collapse. Death occurs in about 1 in
3000 cases. If the patient has very severe breathing
problems before the biopsy, breathing may be slightly
impaired following the operation. If the person’s lungs
were functioning normally before the biopsy, the
chances of any respiratory problems are very small.
Mediastinoscopy
Complications due to mediastinoscopy are rare;
death occurs in fewer than 1 in 3000 cases. More
common complications include lung collapse or bleeding caused by damage to the blood vessels near the
heart. Injury to the esophagus or voice box (larynx)
may sometimes occur. If the nerves leading to the
larynx are injured, the patient may be left with a
permanently hoarse voice. All of these complications
are very rare.

KEY TERMS
Bronchoscopy—A medical test that enables the
doctor to see the breathing passages and the lungs
through a hollow, lighted tube.
Endotracheal tube—A hollow tube that is inserted
into the windpipe to administer anesthesia.
Lymph nodes—Small, bean-shaped structures scattered along the lymphatic vessels which serve as
filters. Lymph nodes retain any bacteria or cancer
cells that are traveling through the system.
Mediastinoscopy—A medical procedure that
allows the doctor to see the organs in the mediastinal space using a thin, lighted, hollow tube (a
mediastinoscope).
Mediastinum—The area between the lungs,
bounded by the spine, breastbone, and diaphragm.
Sputum—Mucus or phlegm that is coughed up
from the passageways (bronchial tubes) in the
lungs.

be due to active infections such as tuberculosis, or
may be scars from a previous infection. The lung cells
on microscopic examination do not resemble normal
cells, and show certain abnormalities that point to
cancer. In a third of biopsies using a mediastinoscope, the lymph nodes that are biopsied prove to
be cancerous. Abnormal results should always be
considered in the context of the patient’s medical
history, physical examination, and other tests such
as sputum examination, chest x rays, etc. before a
final diagnosis is made.
Resources
ORGANIZATIONS

Normal results
Normal results of a needle biopsy and an open
biopsy include the absence of any evidence of infection in the lungs. No lumps or nodules will be
detected in the lungs and the cells will not show any
cancerous abnormalities. Normal results from the
mediastinoscopy will show the lymph nodes to be
free of cancer.

Abnormal results
Abnormal results may be associated with diseases other than cancer. Nodules in the lungs may
GALE ENCYCLOPEDIA OF MEDICINE

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
American Lung Association. 1740 Broadway,
New York, NY 10019. (800) 586-4872.
<http://www.lungusa.org>.
Cancer Research Institute. 681 Fifth Ave., New York, N.Y.
10022. (800) 992-2623. <http://
www.cancerresearch.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Lata Cherath, PhD
2265

Lung biopsy

skin after an open biopsy, the doctor should be notified immediately. The sputum may be slightly bloody
for a day or two after the procedure. If, however, the
bleeding is heavy or persistent, it should be brought to
the attention of the doctor.

Lung cancer, non-small cell

Lung cancer, non-small cell
Definition
Non-small cell lung cancer (NSCLC) is a disease
in which the cells of the lung tissues grow uncontrollably and form tumors.

cancer has developed it frequently spreads to other
parts of the body.
The speed at which non-small cell tumors grow
depends on the type of cells that make up the tumor.
The following three types account for the vast majority of non-small cell tumors:


Adenocarcinomas are the most common and often
cause no symptoms. Frequently they are not found
until they are advanced.



Squamous cell carcinomas usually produce symptoms because they are centrally located and block
the lungs.



Undifferentiated large cell and giant cell carcinomas
tend to grow rapidly, and spread quickly to other
parts of the body.

Description
There are two kinds of lung cancers, primary and
secondary. Primary lung cancer starts in the lung itself,
and is divided into small cell lung cancer and non-small
cell lung cancer. Small cell lung cancers are shaped like
an oat and called oat-cell cancers; they are aggressive,
spread rapidly, and represent 20% of lung cancers.
Non-small cell lung cancer represents almost 80% of
all primary lung cancers. Secondary lung cancer is
cancer that starts somewhere else in the body (for
example, the breast or colon) and spreads to the lungs.
The lungs
The lungs are located along with the heart in the
chest cavity. The lungs are not simply hollow balloons but have a very organized structure consisting
of hollow tubes, blood vessels and elastic tissue. The
hollow tubes, called bronchi, are highly branched,
becoming smaller and more numerous at each
branching. They end in tiny, blind sacs made of
elastic tissue called alveoli. These sacs are where
the oxygen a person breathes in is taken up into the
blood, and where carbon dioxide moves out of the
blood to be breathed out.
Normal healthy lungs are continually secreting
mucus that not only keeps the lungs moist, but also
protects the lungs by trapping foreign particles like
dust and dirt in breathed air. The inside of the lungs
is covered with small hairlike structures called cilia.
The cilia move in such a way that mucus is swept up
out of the lungs and into the throat.
Lung cancer
Most lung cancers start in the cells that line the
bronchi, and can take years to develop. As they grow
larger they prevent the lungs from functioning normally. The tumor can reduce the capacity of the lungs,
or block the movement of air through the bronchi in
the lungs. As a result, less oxygen gets into the blood
and patients feel short of breath. Tumors may also
block the normal movement of mucus up into the
throat. As a result, mucus builds up in the lungs and
infection may develop behind the tumor. Once lung
2266

Worldwide, lung cancer is the most common cancer
in males, and the fifth most common cancer in women.
The worldwide mortality rate for patients with lung
cancer is 86%. In the United States, lung cancer is the
leading cause of death from cancer among both men
and women. The World Health Organization estimates
that the worldwide mortality from lung cancer will
increase to three million by the year 2025. Of those
three million deaths, almost two and a half million will
result from non-small cell lung cancer.
The American Cancer Society (ACS) estimates
that 173,770 Americans will develop lung cancer in
2004, 93,110 men and 80,660 women. Of these
patients, 160,440 will die of the disease.
The incidence of lung cancer is beginning to fall in
developed countries. This may be a result of antismoking campaigns. In developing countries, however,
rates continue to rise, which may be a consequence
of both industrialization and the increasing use of
tobacco products.

Causes and symptoms
Causes
Tobacco smoking accounts for 87% of all lung
cancers. Giving up tobacco can prevent most lung
cancers. Smoking marijuana cigarettes is considered
another risk factor for cancer of the lung. Second
hand smoke also contributes to the development of
lung cancer among nonsmokers.
Certain hazardous materials that people may be
exposed to in their jobs have been shown to cause lung
cancer. These include asbestos, coal products, and
radioactive substances. Air pollution may also be a
contributing factor. Exposure to radon, a colorless,
odorless gas that sometimes accumulates in the
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms
Lung cancers tend to spread very early, and only
15% are detected in their early stages. The chances of
early detection, however, can be improved by seeking
medical care at once if any of the following symptoms
appear:


a cough that does not go away



chest pain



shortness of breath



recurrent lung infections, such as bronchitis or
pneumonia



bloody or brown-colored spit or phlegm (sputum)



persistent hoarseness



significant weight loss that is not due to dieting or
vigorous exercise; fatigue and loss of appetite



unexplained fever

Although these symptoms may be caused by diseases other than lung cancer, it is important to consult
a doctor to rule out the possibility of lung cancer.
If lung cancer has spread to other organs, the
patient may have other symptoms such as headaches,
bone fractures, pain, bleeding, or blood clots.

Diagnosis
Physical examination and diagnostic tests
The doctor will first take a detailed medical history and assess risk factors. During a complete physical examination the doctor will examine the patient’s
throat to rule out other possible causes of hoarseness
or coughing, and will listen to the patient’s breathing
and chest sounds.
If the doctor has reason to suspect lung cancer,
particularly if the patient has a history of heavy smoking or occupational exposure to irritating substances, a
chest x ray may be ordered to see if there are any masses
in the lungs. Special imaging techniques, such as computed tomography (CT) scans or magnetic resonance
imaging (MRI), may provide more precise information
about the size, shape, and location of any tumors.

from the lungs. This test can diagnose at least 30% of
lung cancers, even if tumors are not visible on chest x
rays. In addition, the test can detect cancer in its very
early stages, before it spreads to other regions. The
sputum test does not provide any information about
the location of the tumor.
Lung biopsy
Lung biopsy is the most definitive diagnostic tool
for cancer. It can be performed in three different ways.
Bronchoscopy involves the insertion of a slender,
lighted tube, called a bronchoscope, down the
patient’s throat and into the lungs. This test allows
the doctor to see the tubes inside the lungs, and to
obtain samples of lung tissue. If a needle biopsy is to be
performed, the location of the tumor is first identified
using a computerized tomography (CT) scan or magnetic resonance imaging (MRI). The doctor then
inserts a needle through the chest wall and collects a
sample of tissue from the tumor. In the third procedure, known as surgical biopsy, the chest wall is
opened up and a part of the tumor, or all of it, is
removed. A doctor who specializes in the study of
diseased tissue (a pathologist) examines the tumor to
identify the cancer’s type and stage.

Treatment
Staging
Treatment for non-small cell lung cancer depends
primarily on the stage of the cancer. Staging is a
process that tells the doctor if the cancer has spread
and the extent of its spread. The most commonly used
treatments are surgery, radiation therapy, and
chemotherapy.
Non-small cell lung cancer has six stages:


Occult carcinoma. Cancer cells have been found in
the sputum, but no tumor has yet been found.



Stage 0. A small group of cancerous cells have been
found in one location.



Stage I. The cancer is only in the lung and has not
spread anywhere else.



Stage II. The cancer has spread to nearby lymph
nodes.



Stage III. The cancer has spread to more distant
lymph nodes, and/or other parts of the chest like
the diaphragm.



Stage IV. The cancer has spread to other parts of the
body.

Sputum analysis
Sputum analysis is a noninvasive test that involves
microscopic examination of cells that are coughed up
GALE ENCYCLOPEDIA OF MEDICINE

2267

Lung cancer, non-small cell

basement of homes, may cause lung cancer in a tiny
minority of patients. In addition, patients whose lungs
are scarred from other lung conditions may have an
increased risk of developing lung cancer.

Lung cancer, non-small cell

Surgery
Surgery is the standard treatment for the earlier
stages of non-small cell lung cancer. The surgeon will
decide on the type of surgery, depending on how much
of the lung is affected. There are three different types
of surgical procedures:


Wedge resection is the removal of a small part of the
lung.



Lobectomy is the removal of one lobe of the lung.
(The right lung has three lobes and the left lung has
two lobes.)



Pneumonectomy is the removal of an entire lung.

Lung surgery is a major procedure and patients
can expect to experience pain, weakness in the chest,
and shortness of breath. Air and fluid collect in the
chest after surgery. As a result, patients will need help
to turn over, cough, and breath deeply. Patients
should be encouraged to perform these activities
because they help get rid of the air and fluid and
speed up recovery. It can take patients several months
before they regain their energy and strength.
Radiotherapy
Patients whose cancer has progressed too far for
surgery (Stages III and IV) may receive radiotherapy.
Radiotherapy involves the use of high-energy rays to
kill cancer cells. It is used either by itself or in combination with surgery or chemotherapy. The amount of
radiation used depends on the size and the location of
the tumor.
Radiation therapy may produce such side effects
as tiredness, skin rashes, upset stomach, and diarrhea.
Dry or sore throats, difficulty in swallowing, and loss
of hair in the treated area are all minor side effects of
radiation. These may disappear either during the
course of the treatment or after the treatment is over.
Chemotherapy
Chemotherapy is also given to patients whose
cancer has progressed too far for surgery.
Chemotherapy is medication that is usually given
intravenously to kill cancer cells. These drugs enter
the bloodstream and travel to all parts of the body,
killing cancer cells that have spread to different
organs. Chemotherapy is used as the primary treatment for cancers that have spread beyond the lung and
cannot be removed by surgery. It can also be used in
addition to surgery or radiation therapy.
Chemotherapy for NSCLC has made significant
advances since the early 1980s in improving the
2268

patient’s quality of life as well as length of survival.
Newer cytotoxic (cell-killing) agents developed in the
1990s, such as the taxanes, are typically combined with
either cisplatin or carboplatin as first-line therapy for
non-small cell lung cancer.
Newer drugs for lung cancer developed since 2000
include gefinitib (Iressa) and pemetrexed (Alimta). The
FDA approved gefinitib in May 2003 as a treatment for
patients with NSCLC who have not responded to platinum-based or taxane chemotherapy. It is taken by
mouth and works by inhibiting an enzyme involved in
the growth of tumor cells. Pemetrexed, which is given
by injection, was approved by the FDA in February
2004 for the treatment of mesothelioma, a type of lung
cancer caused by exposure to asbestos fibers. However,
the drug appears to be effective in treating other types
of lung cancer as well.
Chemotherapy is also used as palliative treatment
for non-small cell lung cancer. Palliative refers to any
type of therapy that is given to relieve the symptoms of
a disease but not to cure it.
Chemotherapy for non-small cell lung cancer
often has severe side effects, including nausea and
vomiting, hair loss, anemia, weakening of the immune
system, and sometimes infertility. Most of these side
effects end when the treatment is over. Other medications can be given to lessen the unpleasant side effects
of chemotherapy.

Alternative treatment
Because non-small cell lung cancer has a poor
prognosis with conventional medical treatment,
many patients are willing to try complementary and
alternative therapies. These therapies are used to try
to reduce stress, ease side effects and symptoms, or
control disease. Two treatments sometimes used are
shark cartilage and mistletoe. Although shark cartilage is thought to interfere with the tumor’s blood
supply, clinical trials have so far been inconclusive.
Mistletoe is a poisonous plant that has been shown to
kill cancer cells in the laboratory. Again, however,
clinical trials with cancer patients have been
inconclusive.
Patients who decide to try complementary and
alternative therapies should tell their doctor. Some of
these therapies may interfere with conventional
treatment.

Prognosis
The prognosis for non-small cell lung cancer is
better if the disease is found early, and removed
GALE ENCYCLOPEDIA OF MEDICINE

Skarin, Harry S., editor. Multimodality Treatment of Lung
Cancer. New York: Marcel Dekker, 2000.
PERIODICALS

Bronchi—The tubes that carry air into the lungs.
Lymph—Clear fluid containing white blood cells
that is collected from the tissues of the body and
flows in vessels called the lymphatic system.
Lymph node—Small oval-shaped filters in the lymphatic system that trap bacteria and other
unwanted particles to ensure their removal from
the body.
Palliative—Referring to any type of treatment that
is given to relieve the symptoms of a disease rather
than to cure it.
Respiratory distress—A condition in which
patients with lung disease are not able to get
enough oxygen.

surgically. For patients whose disease is caught in
Stage I, the survival rate five years after surgery ranges
from 60% to 80%. Up to 55% of Stage II patients are
alive after five years, but only about 30% of Stage III
patients make it to five years. Unfortunately, 85% of
patients already have at least Stage III cancer by the
time they are diagnosed. Many of these patients have
disease that is too advanced for surgery. Despite treatment with radiotherapy and chemotherapy, the fiveyear survival for patients with inoperable disease is
extremely low.

Prevention
The best way to prevent lung cancer is not to start
smoking or to quit smoking. Secondhand smoke from
other people’s tobacco should also be avoided.
Appropriate precautions should be taken when working with cancer-causing substances (carcinogens).
Testing houses for the presence of radon gas, and
removing asbestos from buildings have also been suggested as preventive strategies.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Bronchogenic Carcinoma.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Brambilla, Christian, and Elisabeth Brambilla, editors. Lung
Tumors. Fundamental Biology and Clinical
Management. New York: Marcel Dekker, 1999.
GALE ENCYCLOPEDIA OF MEDICINE

Carney, Desmond N., and Heine H. Hansen. ‘‘Non-SmallCell Lung Cancer: Stalemate or Progress?’’ New
England Journal of Medicine 343, no. 17 (26 October
2000): 1261–3.
Cohen, M. H., G. A. Williams, R. Sridhara, et al. ‘‘United
States Food and Drug Administration Drug Approval
Summary: Gefitinib (ZD1839; Iressa) Tablets.’’ Clinical
Cancer Research 10 (February 15, 2004): 1212–1218.
Deslauriers, Jean, and Jocelyn Gregoire. ‘‘Clinical and
Surgical Staging of Non-Small Cell Lung Cancer.’’
Chest 117, no. 4, Supplement 1 (April 2000): 96S–103S.
Fossella, F. V. ‘‘Pemetrexed for Treatment of Advanced
Non-Small Cell Lung Cancer.’’ Seminars in Oncology
31 (February 2004): 100–105.
Frampton, J. E., and S. E. Easthope. ‘‘Gefitinib: A Review
of Its Use in the Management of Advanced Non-SmallCell Lung Cancer.’’ Drugs 64 (2004): 2475–2492.
Johnson, David H. ‘‘Locally Advanced, Unresectable NonSmall Cell Lung Cancer. New Treatment Strategies.’’
Chest 117, no.4, Supplement 1 (April 2000): 123S–126S.
Ramalingam, S., and C. P. Belani. ‘‘State-of-the-Art
Chemotherapy for Advanced Non-Small Cell Lung
Cancer.’’ Seminars in Oncology 31 (February 2004):
68–74.
Rigas, J. R. ‘‘Taxane-Platinum Combinations in Advanced
Non-Small Cell Lung Cancer: A Review.’’ Oncologist 9,
Supplement 2 (2004): 16–23.
ORGANIZATIONS

Alliance for Lung Cancer Advocacy, Support and
Education. PO Box 849 Vancouver, WA 98666. (800)
298-2436. <http://www.alcase.org>.
American Lung Association. 1740 Broadway New York,
NY 10019. (212) 315-8700. <http://
www.lungusa.org>.
National Cancer Institute (National Institutes of Health).
9000 Rockville Pike, Bethesda, MD 20892. (800) 4226237. <http://www.nci.nih.gov>.
National Center for Complementary and Alternative
Medicine (National Institutes of Health). PO Box 8218,
Silver Spring, MD 20907-8218. (888) 644-6226.
<http://nccam.nih.gov>.
OTHER

American Cancer Society (ACS). Cancer Facts & Figures
2004. <http://www.cancer.org/downloads/STT/
CAFF_finalPWSecured.pdf>.
FDA News, February 5, 2004. ‘‘FDA Approves First Drug
for Rare Type of Cancer.’’ <http://www.fda.gov/bbs/
topics/NEWS/2004/NEW01018.html>.

Lata Cherath, PhD
Alison McTavish, M.Sc.
Rebecca J. Frey, PhD
2269

Lung cancer, non-small cell

KEY TERMS

Lung cancer, small cell

Lung cancer, small cell
Definition

annually in the United States, about 40,000 are caused
by small cell lung cancer. Although there are differences in mortality rates between ethnic groups, this is
mainly due to differences in smoking habits.

Small cell lung cancer is a disease in which the cells
of the lung tissues grow uncontrollably and form
tumors.

Description
Lung cancer is divided into two main types: small
cell and non-small cell. Small cell lung cancer is the
least common of the two, accounting for only about
20% of all lung cancers. In the past, the disease was
called oat cell cancer because, when viewed under a
microscope, the cancer cells resemble oats. This type
of lung cancer grows quickly and is more likely to
spread to other organs in the body.
The lungs are located along with the heart in the
chest cavity. The lungs are not simply hollow balloons, but have a very organized structure consisting
of hollow tubes, blood vessels, and elastic tissue. The
hollow tubes, called bronchi, are multi-branched,
becoming smaller and more numerous at each
branching. They end in tiny, blind sacs made of
elastic tissue called alveoli. These sacs are where
the oxygen a person breathes in is taken up into the
blood, and where carbon dioxide moves out of the
blood to be breathed out.
Normal, healthy lungs are continually secreting
mucus that not only keeps the lungs moist, but also
protects the lungs by trapping foreign particles like
dust and dirt in breathed air. The inside of the lungs
is covered with small, hair-like structures called cilia.
The cilia move in such a way that mucus is swept up
out of the lungs and into the throat.
Small cell lung tumors usually start to develop
in the central bronchi. They grow quickly and prevent the lungs from functioning at their full capacity.
Tumors may block the movement of air through
the bronchi in the lungs. As a result, less oxygen
gets into the blood and patients feel short of breath.
Tumors may also block the normal movement of
mucus into the throat. As a result, mucus builds up
in the lungs and infection may develop behind the
tumor.
Lung cancer is a growing global epidemic.
Worldwide, lung cancer is the second most common
cancer among both men and women and is the leading
cause of cancer death in both sexes. The worldwide
mortality rate for patients with lung cancer is 86%. Of
the 160,000 deaths from lung cancer that occur
2270

Causes and symptoms
Causes
Tobacco smoking accounts for nearly 90% of all
lung cancers. The risk of developing lung cancer is
increased for smokers who start at a young age, and
for those who have smoked for a long time. The risk
also increases as more cigarettes are smoked, and
when cigarettes with higher tar content are smoked.
Smoking marijuana cigarettes is also a risk factor for
lung cancer. These cigarettes have a higher tar content
than tobacco cigarettes.
Certain hazardous materials that people may be
exposed to in their jobs have been shown to cause lung
cancer. These include asbestos, coal products, and
radioactive substances. Air pollution may also be a
contributing factor. Exposure to radon, a colorless,
odorless gas that sometimes accumulates in the basement of homes, may cause lung cancer in some
patients. In addition, patients whose lungs are scarred
from other lung conditions may have an increased risk
of developing lung cancer.
Although the exact cause of lung cancer is not
known, people with a family history of lung cancer
appear to have a slightly higher risk of contracting the
disease.
Symptoms
Small cell lung cancer is an aggressive disease that
spreads quickly. Symptoms depend on the tumor’s
location within the lung, and on whether the cancer
has spread to other parts of the body. More than 80%
of small cell lung cancer patients have symptoms for
only three months or less, and few cases are detected
early. The following symptoms are the most commonly reported by small cell lung cancer patients at
the time of their diagnosis:


a persistent cough



chest pain



shortness of breath and wheezing



persistent hoarseness



fatigue and loss of appetite

Although some patients may experience bloody
spit or phlegm, this symptom is more commonly seen
in patients with other types of lung cancer.
GALE ENCYCLOPEDIA OF MEDICINE

Lung cancer, small cell
A normal lung (left) and the lung of a cigarette smoker (right). (Photograph by A. Glauberman, Photo Researchers, Inc. Reproduced
by permission.)

Small cell tumors often press against a large blood
vessel near the lungs called the superior vena cava
(SVC), causing a condition known as SCV syndrome.
This condition may cause patients to retain water,
cough, and have shortness of breath. Because small
cell lung cancer often spreads quickly to the bones and
central nervous system, patients may also have bone
pain, headaches, and seizures.

Diagnosis
If lung cancer is suspected, the doctor will take a
detailed medical history that checks both symptoms and
risk factors. During a complete physical examination,
the doctor will examine the patient’s throat to rule out
other possible causes of hoarseness or coughing, and
listen to the patient’s breathing and the sounds made
when the patient’s chest and upper back are tapped. A
chest x ray may be ordered to check for masses in the
lungs. Special imaging techniques, such as computed
tomography (CT) scans or magnetic resonance imaging
(MRI), may provide more precise information about
the size, shape, and location of any tumors.
GALE ENCYCLOPEDIA OF MEDICINE

Sputum analysis involves microscopic examination of the cells that are either coughed up from the
lungs, or are collected through a special instrument
called a bronchoscope. The sputum test does not,
however, provide any information about the location of the tumor and must be followed by other
tests.
Lung biopsy is the most definitive diagnostic tool
for cancer. It can be performed in several different
ways. The doctor can perform a bronchoscopy, which
involves the insertion of a slender, lighted tube, called
a bronchoscope, down the patient’s throat and into
the lungs. In addition to viewing the passageways of
the lungs, the doctor can use the bronchoscope to
obtain samples of the lung tissue. In another procedure known as a needle biopsy, the location of the
tumor is first identified using a CT scan or MRI. The
doctor then inserts a needle through the chest wall and
collects a sample of tissue from the tumor. In the third
procedure, known as surgical biopsy, the chest wall is
opened up and a part of the tumor, or all of it, is
removed for examination.
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Lung cancer, small cell

Treatment
Staging
Staging procedures are important in lung cancer
because they tell doctors whether patients have disease
only in their lungs, or whether the cancer has spread to
other parts of the body. To establish the cancer stage,
doctors have to perform various tests. These may
include bone marrow aspiration and biopsy, CT scans
of the chest and abdomen, MRI scans of the brain, and
radionuclide bone scans. All of these tests determine
the extent to which the cancer has spread. Once the
stage is determined, doctors can decide on a course of
treatment, and can have a better idea of the patient’s
prognosis.
Unlike other types of lung cancer, the staging of
small cell lung cancer is relatively simple. This is
because approximately 70% of patients already have
metastatic disease when they are diagnosed, and small
differences in the amount of tumor found in the lungs
do not change the prognosis. Small cell lung cancer is
usually divided into three stages:


Limited stage: The cancer is found only in one lung
and in lymph nodes close to the lung.



Extensive stage: The cancer has spread beyond the
lungs to other parts of the body.



Recurrent stage: The cancer has returned following
treatment.

Without treatment, small cell lung cancer has the
most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of
only 2–4 months. Compared with other cell types of
lung cancer, small cell lung cancer has a greater tendency to be widely disseminated by the time of diagnosis, but is much more responsive to chemotherapy
and irradiation.
Treatment of small cell lung cancer depends on
whether the patient has limited, extensive, or recurrent
disease. Treatment usually involves radiotherapy and
chemotherapy. Surgery is rarely used for this type of
lung cancer because the tumor is usually too advanced.
Patients with limited-stage disease are usually
treated with chemotherapy. Combinations of two or
more drugs have a better effect than treatment with a
single drug. Up to 90% of patients with this stage of
disease will respond to chemotherapy. The chemotherapy most commonly prescribed is a combination of the
drugs etoposide (Vepesid) and cisplatin (Platinol).
Combining chemotherapy with chest radiotherapy
and/or occasionally surgery has also prolonged survival for limited-stage patients.
2272

An x-ray image showing an oval-shaped carcinoma in the left
lung (right of image). (Custom Medical Stock Photo. Reproduced
by permission.)

In addition to chest radiotherapy, some patients
are also treated with radiation therapy to the brain,
even if no cancer is found there. This treatment, called
prophylactic cranial irradiation (PCI), is given to prevent tumors from forming in the brain. The combination of etoposide and cisplatin chemotherapy with
chest radiation therapy and PCI has increased the
two-year survival of limited-stage small cell lung cancer patients to almost 50%.
Combinations of different chemotherapy agents
are also used for treating extensive-stage small cell
lung cancer. However, compared with limited-stage
patients, the percentage of extensive-stage patients
who respond to therapy is lower. Commonly used
drug combinations include cyclophosphamide
(Cytoxan), doxorubicin (Adriamycin), and vincristine
(Oncovin), or etoposide and cisplatin. The addition of
radiation therapy to chemotherapy does not improve
GALE ENCYCLOPEDIA OF MEDICINE

Bronchi—Hollow tubes that carry air into the
lungs.
PCI—A type of radiotherapy that is used to prevent
tumors from growing in the brain.
Radionuclide bone scan—A test that tells if cancer
has spread to the bones.
Superior vena cava (SVC) syndrome—A condition
seen in lung cancer patients where the tumor
presses against a large blood vessel and causes
various symptoms.

survival in these patients. However, radiation therapy
is used for the palliative (pain relief) treatment of
symptoms of metastatic lung cancer, particularly
brain and bone tumors.
Patients who have recurrent small cell lung cancer
often become resistant to chemotherapy. These
patients are treated with palliative radiotherapy.
Their doctor may also recommend that they take
part in a clinical trial of a new therapy. Patients
whose relapse occurs more than six months after
their initial treatment, however, may still respond to
traditional chemotherapy.
Alternative treatment
Many cancer patients have tried using shark cartilage to treat their disease. Shark cartilage is thought to
interfere with the tumor’s blood supply. A clinical trial
using this treatment in lung cancer patients is ongoing.
Information on this and other alternative treatments is
available on the Internet from the National Center for
Complementary and Alternative Medicine.
Patients who decide to try complementary and
alternative therapies should tell their doctor. Some of
these therapies may interfere with conventional
treatment.

Prognosis
Small cell lung cancer is a very aggressive disease.
Without treatment, limited-stage patients will survive
for three to six months, while extensive-stage patients
will survive six to 12 weeks. However, small cell lung
cancer is much more responsive to chemotherapy and
radiation therapy than other types of lung cancer.
Among patients treated with chemotherapy, 70–90%
have a major response to treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Survival in patients responding to therapy is four
to five times longer than in patients without treatment.
In addition, two years after the start of therapy, about
10% of patients remain free of disease. In general,
women tend to have a better prognosis than men.
Patients whose disease has spread to the central nervous system or liver have a much worse prognosis.
Although the overall survival at five years is 5% to
10%, survival is higher in patients with limited stage
disease. About 70% of patients who are disease free
after two years do not relapse. After five to 10 diseasefree years, relapses are rare.

Prevention
The best way to prevent lung cancer is either not
start smoking, or quit smoking. Secondhand smoke
from other people’s tobacco should also be avoided.
Appropriate precautions should be taken when working with substances that can cause cancer (carcinogens). Testing houses for the presence of radon gas,
and removing asbestos from buildings have also been
suggested as preventive strategies.
Resources
BOOKS

Pass, Harvey I., et al. Lung Cancer Principles and Practice.
Philadelphia: Lippincott Williams and Wilkins, 2000.
PERIODICALS

Adjei, Alex A., et al. ‘‘Current Guidelines for the
Management of Small Cell Lung Cancer.’’ Mayo Clinic
Proceedings 74 (August 1999): 809-16.
Sandler, Alan. ‘‘Extensive Small Cell Lung Cancer: A
Treatment Overview.’’ Oncology 14, no. 7, Supplement
5 (July 2000): 49-55.
Tamura, Tomohide. ‘‘New State of the Art in Small Cell
Lung Cancer.’’ Oncology 15, no. 1, Supplement 1
(January 2001): 8-10.
ORGANIZATIONS

Alliance for Lung Cancer Advocacy, Support, and
Education. P.O. Box 849, Vancouver, WA 98666. (800)
298-2436. <http://www.alcase.org>.
American Lung Association.1740 Broadway New York, NY
10019. (212) 315-8700. <http://www.lungusa.org>.
National Cancer Institute (National Institutes of Health).
9000 Rockville Pike, Bethesda, MD 20892. (800) 4226237. <http://www.nci.nih.gov>.
National Center for Complementary and Alternative
Medicine (National Institutes of Health). P.O. Box
8218, Silver Spring, MD 20907-8218. (888) 644-6226.
<http://nccam.nih.gov>.

Lata Cherath, PhD
Alison McTavish, MSc
2273

Lung cancer, small cell

KEY TERMS

Lung diseases due to gas or chemical exposure



There are many organic dusts that irritate the lungs.
Most of them occur on the job and cause occupational lung disease. Grain dust causes silo filler’s
disease. Cotton and other textile dusts cause byssinosis. Mold spores in hay cause farmer’s lung.



Inorganic dusts and aerosolized chemicals also are
found mostly on the job. Classic among them are
asbestos and coal dust. Many metals (cadmium,
arsenic, chromium, and phosphorus), various other
fine particles (cement, mica, rock), acid fumes,
ammonia, ozone, and automobile and industrial
emissions are part of a very long list.



While tobacco smoke is a culprit in many smokers, a
2003 report found that those who work in the
tobacco industry experience higher incidence of
lung disease from tobacco dust in their work
environment.



Most intentional poisons (cyanide, nerve gas) that
enter through the lungs pass through and damage
other parts of the body. Mustard gas, used during
World War I and banned since, directly and immediately destroys lungs.



Tobacco use scars the lungs and causes emphysema
and lung cancer.

Lung diseases due to gas
or chemical exposure
Definition
Lung diseases due to gas or chemical exposure
are conditions that can be acquired from indoor and
outdoor air pollution and from ingesting tobacco
smoke.

Description
The lungs are susceptible to many airborne poisons and irritants. Mucus present in the airways
blocks foreign particles of a certain size, however it is
unable to filter all airborne particulates. There are
hundreds of substances that can pollute air and harm
lungs. Harmful gases and chemicals are just one type
of airborne pollutant that can adversely affect the
lungs. They include:


Vehicle exhaust



Localized pollutants such as arsenic, asbestos, lead,
and mercury



Outdoor pollutants caused by industry and intensified by weather conditions



Household heating, such as wood-burning stoves



Household chemical products



Tobacco smoke.

Lungs respond to irritants in four ways, each of
which can occur separately or, more often, trigger
other responses.


Asthma occurs when irritation causes the smooth
muscles surrounding the airways to constrict.



Increased mucus comes from irritated mucus glands
lining the airway. Excess mucus clogs the airway and
prevents air from circulating.



Constriction of the lungs results from scarring when
the supporting tissues are damaged.



Cancer is caused by certain irritants, such as asbestos
and tobacco smoke.

The major categories that airborne irritants fall
into are allergic, organic, inorganic, and poisonous,
with many agents occupying more than one category.


Allergic irritants bother only people who are sensitive to them. Cat hair, insect parts, and pollen are
common allergens. Chemicals called sulfites, which
are widely used as food preservatives, also cause
asthma.

2274

Causes and symptoms
Lung disease generates three major symptoms–
coughing, wheezing, and shortness of breath. It also
predisposes the lungs to infections such as bronchitis
and pneumonia. Cancer is a late effect, requiring prolonged exposure to an irritant. In the case of tobacco,
an average of a pack of cigarettes a day for forty years,
or two packs a day for twenty years, will greatly
increase the risk of lung cancer.

Diagnosis
A history of exposure combined with a chest x ray
and lung function studies completes the diagnostic evaluation in most cases. Lung function measures the
amount of air breathed in and out, the speed it moves,
and the effectiveness of oxygen exchange with the blood.
If the cause still is unclear, a lung biopsy aids diagnosis.

Treatment
Eliminating the offending irritant and early antibiotics for infection are primary. There are many techniques available to remove excess mucus from the
lungs. Respiratory therapists are trained in these
methods. Finally, there are several machines available
to enrich the oxygen content of breathed air.
GALE ENCYCLOPEDIA OF MEDICINE

Allergen—A substance that causes an allergic reaction in those who are sensitive to it.
Asthma—Temporary airway narrowing that causes
wheezing and shortness of breath due to allergies.
Bronchitis—Infection in the bronchi (breathing
tubes).
Pneumonia—Infection or inflammation in the lung
itself.

Lung function tests see Pulmonary function
test

Lung perfusion and ventilation
scan
Definition

A surgical treatment called lung reduction volume
surgery is emerging as a treatment for certain people
over age 65 with severe emphysema. It promises substantial return of lung function for selected patients
by cutting away diseased parts of the lungs so that
healthy tissue functions better. In the fall of 2003,
Medicare announced that it would begin paying for
the surgery.

Prognosis
Many of these diseases are progressive, because
the irritants stay in the lungs forever. Others remain
stable after the offensive agents are removed from the
environment. Lungs do not heal from destructive
damage, but they can clean out infection and excess
mucus, and function better.

Prevention
Industrial air filters, adequate ventilation, and
respirators in polluted work sites now are mandatory.
Tobacco smoke is the world’s leading cause of lung
disease and many other afflictions. Smoking cessation
programs are widely available.
Resources
PERIODICALS

‘‘Medicare Will Cover Lung Volume Reduction Surgery for
Certain Patients.’’ Health & Medicine Week October 20,
2003: 245.
Mustajbegovic, Jadranka, et al. ‘‘Respiratory Findings in
Tobacco Workers.’’ Chest May 2003: 1740-1749.
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.

J. Ricker Polsdorfer, MD
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

A lung perfusion scan is a nuclear medicine test
that produces a picture of blood flow to the lungs. A
lung ventilation scan measures the ability of the lungs
to take in air and uses radiopharmaceuticals to produce a picture of how air is distributed in the lungs.

Purpose
Lung perfusion scans and lung ventilation scans
are usually performed in the same session. They are
done to detect pulmonary embolisms, determine how
much blood is flowing to lungs, determine which areas
of the lungs are capable of ventilation, and assess how
well the lungs are functioning after surgery. These tests
are called by different names, including perfusion lung
scan, aerosol lung scan, radionucleotide ventilation
lung scan, ventilation lung scan, xenon lung scan,
ventilation/perfusion scanning (VPS), pulmonary
scintiphotography, or, most commonly, V/Q scan.

Precautions
The amount of radioactivity a person is exposed
to during these tests is very low and is not harmful.
However, if the patient has had other recent radionuclear tests, it may be necessary to wait until other
radiopharmaceuticals have been cleared from the
body so that they do not interfere with these tests.

Description
In a lung perfusion scan, a small amount of the
protein labeled with a radioisotope is injected into the
patient’s hand or arm vein. The patient is positioned
under a special camera that can detect radioactive
material, and a series of photographs are made of the
chest. When these images are projected onto a screen
(oscilloscope), they show how the radioactive protein
has been distributed by the blood vessels running
through the lungs.
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Lung perfusion and ventilation scan

Lung fluke infections see Fluke infections

KEY TERMS

Lung surgery

Resources

KEY TERMS
Pulmonary embolism—A blood clot in the arteries
going to the lungs.

BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Tish Davidson, A.M.

In a lung ventilation scan, a mask is placed over
the nose and mouth, and the patient is asked to
inhale and exhale a combination of air and radioactive gas. Pictures are then taken that show the
distribution of the gas in the lungs. Each test takes
15-30 minutes.

Preparation
There is little preparation needed for these tests.
The patient may eat and drink normally before the
procedure. Tests to check for pulmonary embolism are
often performed on an emergency basis.

Lung surgery
Definition
Lung surgery includes a variety of procedures
used to diagnose or treat diseases of the lungs.
Biopsies are performed to extract a small amount of
tissue for diagnosis, resections remove a portion of
lung tissue, and other surgeries are aimed at reducing
the volume of the lungs, removing cancerous tumors,
or improving lung function.

Purpose

Aftercare
No special aftercare is needed. The patient may
resume normal activities immediately.

Risks

The type of lung surgery performed will depend
upon the underlying disease or condition, as well as
other factors.


Pneumonectomy usually refers to the removal of a
lung, or sometimes one or more lobes (sections containing lung tissue, air sacs, ducts, and respiratory
bronchiole). It is most commonly indicated in certain
forms and stages of lung cancer.



Thoracotomy, or surgical incision of the chest wall, is
used primarily as a diagnostic tool when other procedures have failed to provide adequate diagnostic
information.



Lobectomy is the term used to describe removal of
one lobe of a lung. It is most commonly indicated for
lung cancer, but may also be used for cystic fibrosis
patients if other treatments have failed.



Other surgical procedures include segmental resection or wedge resection. A resection is the removal of
a part of the lung, often in order to remove a tumor.
Wedge resection is removal of a wedge-shaped portion of lung tissue.



Volume reduction surgery is a newer surgery used to
help relieve shortness of breath and increase tolerance
for exercise in patients with chronic obstructive pulmonary disease, such as emphysema.



Other surgeries are continuously improved upon to
make biopsy less invasive and surgery more effective,
such as video-assisted lobectomy. Other purposes for

There are practically no risks associated with
these tests.

Normal results
Normal results in both tests show an even distribution of radioactive material in all parts of the
lungs.

Abnormal results
In the lung perfusion scan, an absence of radioactive marker material suggests decreased blood flow
to that part of the lung, and possibly a pulmonary
embolism. However, pneumonia, emphysema, or lung
tumors can create readings on the lung perfusion
scan that falsely suggest a pulmonary embolism is
present.
In the lung ventilation scan, absence of marker
material when the lung perfusion scan for the area is
normal suggests lung disease.
Certain combinations of abnormalities in lung
perfusion and ventilation scans suggest pulmonary
embolism.
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GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Thoracotomy should not be performed on
patients whose general health status will not tolerate
major surgery. Any surgery carries with it risks associated with general anesthesia and possibility of infection. Patients whose risk for these complications
outweighs benefit may not be considered candidates
for lung surgery. Each individual patient’s condition
will be reviewed prior to the treatment decision.

Description
Lung surgery procedures will vary depending on
the underlying cause of the surgical test or intervention. A patient will be placed under general anesthesia
during the surgery. An incision is made to examine the
lungs. Diseased tissue is removed and may be sent for
biopsy. Following the surgery, drainage tubes may be
placed in the chest to drain fluids, blood, and air from
the chest cavity. Tubes will most likely remain in place
for one to two days, depending on the surgery and the
patient’s condition. The chest cavity, ribs, and skin are
closed and the incision will be sutured. Hospital stay
averages from three to 10 days.
Pneumonectomy consists of removal of all of one
lung. It may often be indicated only when a lobectomy
does not successfully remove the cancerous or
damaged tissue. Thoracotomy consists of reaching
the lung tissue through incision and obtaining tissue
for a biopsy. The biopsy is used to diagnose or stage
cancer, and thoracotomy may be avoided until other
less invasive methods have failed. Volume reduction
surgery involves incision and removal of those parts of
the lung or lungs which are the most destroyed, in
order to allow for full function of the remaining lung
structure. This procedure is still being studied.
Lobectomy is performed in the same general manner as other lung surgeries, but will involve removal of
an entire lobe of the lung. Most patients with Stage I
or II non-small cell lung cancer will receive this treatment for their disease, or a less extensive resection.
Lobectomy may only be performed if a wedge or segmental resection is ineffective, but is generally preferred as treatment for primary lung cancer in any
patient who can tolerate the procedure. Wedge and
segmental resections are still major surgery, but
remove less tissue and may be the first choice for
some patients, such as those with Stage I and Stage
GALE ENCYCLOPEDIA OF MEDICINE

II non-small cell lung cancer. Patients who do not have
enough pulmonary function to undergo a lobectomy
will receive a wedge or segmental resection instead.
This may lead to a higher recurrence rate of cancer.
In general, the surgery method chosen will depend on
specific circumstances and consideration of benefit
versus risk.

Preparation
Preparation for lung surgery is much like that for
any major surgery. Patients will receive instructions
from a physician concerning limit of food or water
intake prior to the surgery, as well as risks and
expected recovery. Patients should continue to follow
treatment for the underlying condition, unless
instructed otherwise by the physician, and should discuss medications and changes in condition with their
physician prior to the surgery.

Aftercare
The chest tube inserted at the end of surgery will
remain in place until the lung has fully expanded.
Patients will be carefully monitored in the hospital
for complications and infection. Deep breathing is
recommended to help lessen the risk of pneumonia
and infection. Breathing exercises will also help
expand the lung. After discharge from the hospital,
the patient may still receive some pain or infectionfighting medications and should recover within one to
three months of the operation.

Risks
Risks of lung surgery follows those of any major
surgery involving general anesthesia. These risks
include reactions to anesthetics or medications, bleeding, infection, and problems restoring breathing. Lung
surgery, in particular, offers the risk of pneumonia
and blood clots. Thoracotomy, as a biopsy procedure,
offers greater risk than most biopsy procedures.

Normal results
Outcome for any lung surgery depends on many
factors and the severity of disease. In general, the
predicted benefits, which justified the surgery, are
normal expected results. Thoracotomy results in a
definitive diagnosis in more than 90% of patients.
Volume reduction surgery has been shown to result
in relief of some symptoms and improvement in quality of life for selected patients with severe emphysema
and have shown short-term promise.
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Lung surgery

lung surgery may include severe abscess, areas of
long-term infection, or permanently enlarged or collapsed lung tissue.

Lung transplantation

Mortality from lung surgery improves as procedures move from the more complete pneumonectomy
to lobectomy, and the lowest rate for segmental
resection.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Teresa Odle

National Transplant Waiting List By Organ Type (June 2000)

Organ Needed

Number Waiting

Kidney
Liver
Heart
Lung
Kidney-Pancreas
Pancreas
Heart-Lung
Intestine

48,349
15,987
4,139
3,695
2,437
942
212
137

disease) with cor pulmonale should be considered as
early as possible for lung transplantation. Other indicators of lung transplantation include pulmonary vascular disease and chronic pulmonary infection.

Precautions

Lung transplantation
Definition
Lung transplantation involves removal of one or
both diseased lungs from a patient and the replacement of the lungs with healthy organs from a donor.
Lung transplantation may refer to single, double, or
even heart-lung transplantation.

Purpose
The purpose of lung transplantation is to replace a
lung that no longer functions, or is cancerous, with a
healthy lung. In order to qualify for lung transplantation, a patient must suffer from severe lung disease
which limits activities of daily living. There should be
potential for rehabilitated breathing function.
Attempts at other medical treatments should be
exhausted before transplantion is considered. Many
candidates for this procedure have end-stage fibrotic
lung disease, are dependent on oxygen therapy, and are
likely to die of their disease in 12-18 months.
Patients with emphysema or chronic obstructive
pulmonary disease (COPD) should be under 60 years
of age, have a life expectancy without transplantation
of two years or less, progressive deterioration, and
emotional stability in order to be considered for lung
transplantation. Young patients with end-stage silicosis (a progressive lung disease) may be candidates for
lung or heart-lung transplantation. Patients with
Stage III or Stage IV sarcoidosis (a chronic lung
2278

Patients who have diseases or conditions which
may make them more susceptible to organ rejection
should not receive a lung transplant. This includes
patients who are acutely ill and unstable; who have
uncontrolled or untreatable pulmonary infection; significant dysfunction of other organs, particularly the
liver, kidney, or central nervous system; and those with
significant coronary disease or left ventricular dysfunction. Patients who actively smoke cigarettes or are
dependent on drugs or alcohol may not be selected.
There are a variety of protocols that are used to determine if a patient will be placed on a transplant recipient
list, and criteria may vary depending on location.

Description
Once a patient has been selected as a possible organ
recipient, the process of waiting for a donor organ
match begins. The donor organ must meet clear
requirements for tissue match in order to reduce the
chance of organ rejection. It is estimated that it takes an
average of one to two years to receive a suitable donor
lung, and the wait is made less predictable by the necessity for tissue match. Patients on a recipient list must be
available and ready to come to the hospital immediately
when a donor match is found, since the life of the lungs
outside the body is brief.
Single lung transplantation is performed via a standard thoracotomy (incision in the chest wall) with the
patient under general anesthesia. Cardiopulmonary
bypass (diversion of blood flow from the heart) is not
always necessary for a single lung transplant. If bypass
GALE ENCYCLOPEDIA OF MEDICINE

Heart-lung transplants always require the use of
cardiopulmonary bypass. An incision is made through
the middle of the sternum. The heart, lung, and supporting structures are transplanted into the recipient
at the same time.

Preparation
In addition to tests and criteria for selection as a
candidate for transplantation, patients will be prepared
by discussing the procedure, risks, and expected prognosis at length with their doctor. Patients should
continue to follow all therapies and medications for
treatment of the underlying disease unless otherwise
instructed by their physician. Since lung transplantation takes place under general anesthesia, normal surgical and anesthesia preparation should be taken when
possible. These include no food or drink from midnight
before the surgery, discussion of current medications
with the physician, and informing the physician of any
changes in condition while on the recipient waiting list.

Aftercare
Careful monitoring will take place in a recovery
room immediately following the surgery and in the
patient’s hospital room. Patients must take immunosuppression, or anti-rejection, drugs to reduce the risk
of rejection of the transplanted organ. The body considers the new organ an invader and will fight its
presence. The anti-rejection drugs lower the body’s
immune function in order to improve acceptance of
the new organs. This also makes the patient more
susceptible to infection.
Frequent check-ups with a physician, including x
ray and blood tests, will be necessary following surgery, probably for a period of several years.

Risks
Lung transplantation is a complicated and risky
procedure, partly because of the organs and systems
involved, and also because of the risk of rejection by
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Pulmonary—Refers to the respiratory system, or
breathing function and system.
Sarcoidosis—A chronic disease with unknown
cause that involves formation of nodules in bones,
skin, lymph nodes, and lungs.
Silicosis—A progressive disease that results in
impairment of lung function and is caused by inhalation of dust containing silica.

the recipient’s body. Acute rejection most often occurs
within the first four months following surgery, but
may occur years later. Infection is a substantial risk
for organ recipients. An early complication of the
surgery can be poor healing of the bronchial and
tracheal openings created during the surgery. A late
complication and risk is chronic rejection. This can
result in inflammation of the bronchial tubes or in late
infection from the prolonged use of immunosuppressant drugs to fight rejection. Overall, lung transplant
recipients have demonstrated average one and twoyear survival rates of more than 70%.

Normal results
The outcome of lung transplantation can be measured in survival rates, and also in improved quality of
life for recipients. Studies have reported improved
quality of life after lung and heart-lung transplants.
One study showed that at the two-year follow-up period, 86% of studied recipients reported no limitation
to their activity. Demonstration of normal results for
patients may include quality of life measurements, as
well as testing to ensure lack of infection and rejection.
Resources
ORGANIZATIONS

Children’s Organ Transplant Association, Inc. 2501 COTA
Drive, Bloomington, IN 47403. (800) 366-2682.
<http://www.cota.org>.
Second Wind Lung Transplant Association, Inc. 9030 West
Lakeview Court, Crystal River, FL 34428. (888) 2222690. <http://www.arthouse.com/secondwind>.

Teresa Odle

Lupus erythematosus see Systemic lupus
erythematosus
Luque rod see Spinal instrumentation
2279

Lung transplantation

is necessary, it involves re-routing of the blood through
tubes to a heart-lung bypass machine. Double lung
transplantation involves implanting the lungs as two
separate lungs, and cardiopulmonary bypass is usually
required. The patient’s lung or lungs are removed and
the donor lungs are stitched into place. Drainage tubes
are inserted into the chest area to help drain fluid,
blood, and air out of the chest. They may remain in
place for several days. Transplantation requires a long
hospital stay and recovery can last up to six months.

Luteinizing hormone test

KEY TERMS

Luteinizing hormone test
Definition
The luteinizing hormone (LH) test is a test of the
blood or urine to measure the level of luteinizing hormone (lutropin). This hormone level is highest immediately before a woman ovulates during her menstrual
cycle.

Lutropin—Another term for luteinizing hormone,
this hormone stimulates the development and
release of the egg from the ovary.

Preparation
Purpose
The LH test is frequently used to determine the
timing of ovulation. Couples who are trying to become
pregnant may use information about the timing of
ovulation to improve their chance of conception. The
LH test and other hormone tests may be used during
infertility screening to chart a woman’s menstrual
cycle. It may also be used during preparation for in
vitro fertilization, to determine when eggs are mature
and ready to be removed from the ovary.

Description
Lutenizing hormone is a hormone released by the
pituitary gland, a small gland at the base of the brain.
The hormone stimulates the ovaries to produce and
release eggs each month during the menstrual cycle.
The level of LH in the blood is highest before ovulation. This increase in hormone level is sometimes
called a ‘‘surge.’’ A urine or blood sample can be
analyzed by a laboratory for the level of LH present.
An LH test may be used as part of an infertility screening to determine if there is a hormonal imbalance that
might make it difficult to become pregnant. If fertility
drugs are given to stimulate ovulation, an LH test can
help determine the best time for sexual intercourse.
The LH test may also be used to determine when
eggs are mature enough to be surgically removed
from the ovary as part of the in vitro fertilization
process. LH tests may also aid in the diagnoses of
polycystic ovary disease, premature ovarian failure,
and menopause.
A urine LH detection kit is also available for use
at home. These are sometimes called ‘‘ovulation tests’’
and are similar to home pregnancy test kits. A sample
of the woman’s first morning urine is tested with the
materials provided in the kit. These home tests are
often used by women who want to become pregnant.
By monitoring levels of LH and watching for the
‘‘surge,’’ they can time sexual intercourse to coincide
with ovulation, increasing the chance that the egg will
be fertilized.
2280

If a blood sample is taken, the skin around the
vein where the needle will be inserted is swabbed with
an antiseptic. No special preparation is necessary for
collection of a urine sample.

Aftercare
No special aftercare is required. If the blood is
tested, as with any blood sampling, the area where
the needle was inserted should be kept clean.

Risks
There are no significant risks associated with
either the blood or urine test for LH.

Normal results
The level of LH in the blood or urine will vary
depending on when the sample was taken during the
menstrual cycle. LH levels will be highest around the
time of ovulation, about halfway between a woman’s
menstrual periods. Levels will be lower during the rest
of the month. Women who have already experienced
menopause will normally have lower LH levels.

Abnormal results
LH levels that remain low throughout the menstrual cycle may indicate a hormonal imbalance that
could prevent ovulation. Additional testing may be
required if this test is done as part of an infertility
screening.
Resources
BOOKS

Zaret, Barry L., et al., editors. The Patient’s Guide to Medical
Tests. Boston: Houghton Mifflin, 1997.

Altha Roberts Edgren

Lyme borreliosis see Lyme disease
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Lyme disease is an infection transmitted by the
bite of ticks carrying the spiral-shaped bacterium
Borrelia burgdorferi. The disease was named for
Lyme, Connecticut, the town where it was first diagnosed in 1975 after a puzzling outbreak of arthritis.
The organism was named for its discoverer, Willy
Burgdorfer. The effects of this disease can be longterm and disabling unless it is recognized and treated
properly with antibiotics.

Description
Lyme disease, which is also called Lyme borreliosis, is a vector-borne disease. This term means that it is
delivered from one host to another. It is also classified
as a zoonosis, which means that it is a disease of
animals that can be transmitted to humans under
natural conditions. In this case, a tick bearing the
Borrelia burgdorferi organism literally inserts it into a
host’s bloodstream when it bites the host to feed on its
blood. It is important to note that neither Borrelia
burgdorferi nor Lyme disease can be transmitted
directly from one person to another, or from pets to
humans.
Controversy clouds the true incidence of Lyme
disease because no test is definitively diagnostic for
the disease, and many of its symptoms mimic those of
so many other diseases. Cases of Lyme disease have
been reported in 49 of the 50 states; however, 92% of
the 17,730 cases reported to the Centers for Disease
Control and Prevention (CDC) in 2000 were from
only nine states (Connecticut, Rhode Island, New
York, Pennsylvania, Delaware, New Jersey,
Maryland, Massachusetts, and Wisconsin). The disease is also found in Scandinavia, continental
Europe, the countries of the former Soviet Union,
Japan, and China; in addition, it is possible that it
has spread to Australia.
In the United States, Lyme disease accounts for
more than 90% of all reported vector-borne illnesses.
It is a significant public health problem and continues
to be diagnosed in increasing numbers. The Centers
for Disease Control and Prevention (CDC) attributes
this increase to the growing size of the deer herd and
the geographical spread of infected ticks rather than
to improved diagnosis. In addition, some epidemiologists believe that the actual incidence of Lyme disease in the United States may be 5–10 times greater
GALE ENCYCLOPEDIA OF MEDICINE

The risk for acquiring Lyme disease varies,
depending on what stage in its life cycle a tick has
reached. A tick passes through three stages of development—larva, nymph, and adult—each of which is
dependent on a live host for food. In the United
States, Borrelia burgdorferi is borne by ticks of several species in the genus Ixodes, which usually feed on
the white-footed mouse and deer (and are often
called deer ticks). In the summer, the larval ticks
hatch from eggs laid in the ground and feed by
attaching themselves to small animals and birds. At
this stage they are not a problem for humans. It is the
next stage—the nymph—that causes most cases of
Lyme disease. Nymphs are very active from spring
through early summer, at the height of outdoor activity for most people. Because they are still quite small
(less than 2 mm), they are difficult to spot, giving
them ample opportunity to transmit Borrelia burgdorferi while feeding. Although far more adult ticks
than nymphs carry Borrelia burgdorferi, the adult
ticks are much larger, more easily noticed, and
more likely to be removed before the 24 hours or
more of continuous feeding needed to transmit
Borrelia burgdorferi.

Causes and symptoms
Lyme disease is caused by Borrelia burgdorferi.
Once Borrelia burgdorferi gains entry to the body
through a tick bite, it can move through the bloodstream quickly. Only 12 hours after entering the
bloodstream, Borrelia burgdorferi can be found in cerebrospinal fluid (which means it can affect the nervous
system). Treating Lyme disease early and thoroughly
is important because Lyme disease can hide for long
periods within the body in a clinically latent state.
That ability explains why symptoms can recur in
cycles and can flare up after months or years, even
over decades. It is important to note, however, that
not many people who are exposed to Borrelia burgdorferi develops the disease.
Lyme disease is usually described in terms of
length of infection (time since the person was bitten
by a tick infected with Lyme disease) and whether
Borrelia burgdorferi is localized or disseminated
(spread through the body by fluids and cells carrying
Borrelia burgdorferi). Furthermore, when and how
symptoms of Lyme disease appear can vary widely
from patient to patient. People who experience
2281

Lyme disease

Lyme disease

than that reported by the CDC. The reasons for this
difference include the narrowness of the CDC’s case
definition as well as frequent misdiagnoses of the
disease.

Lyme disease
The first sign of Lyme disease is usually an itchy rash around the site of the tick bite. (Science Photo Library. Custom Medical Stock
Photo. Reproduced by permission.)

recurrent bouts of symptoms over time are said to
have chronic Lyme disease.
Early localized Lyme disease
The most recognizable indicator of Lyme disease
is a rash around the site of the tick bite. Often, the tick
exposure has not been recognized. The eruption might
be warm or itch. The rash—erythema migrans (EM)generally develops within 3-30 days and usually begins
as a round, red patch that expands outward. About
75% of patients with Lyme disease develop EM.
Clearing may take place from the center out, leaving
a bull’s-eye effect; in some cases, the center gets redder
instead of clearing. The rash may look like a bruise on
people with dark skin. Of those who develop Lyme
disease, about 50% notice flu-like symptoms, including fatigue, headache, chills and fever, muscle and joint
pain, and lymph node swelling. However, a rash at the
site can also be an allergic reaction to the tick saliva
rather than an indicator of Lyme disease, particularly
if the rash appears in less than three days and disappears only days later.

2282

Late disseminated disease and chronic Lyme
disease
Weeks, months, or even years after an untreated
tick bite, symptoms can appear in several forms,
including:


Fatigue, forgetfulness, confusion, mood swings,
irritability, numbness.



Neurologic problems, such as pain (unexplained and
not triggered by an injury), Bell’s palsy (facial paralysis, usually one-sided but may be on both sides), and
a mimicking of the inflammation of brain membranes known as meningitis; (fever, severe headache).



Arthritis (short episodes of pain and swelling in
joints) and other musculoskeletal complaints.
Arthritis eventually develops in about 60% of
patients with untreated Lyme disease.

Less common effects of Lyme disease are heart
abnormalities (such as irregular rhythm or cardiac
block) and eye abnormalities (such as swelling of the
cornea, tissue, or eye muscles and nerves).

GALE ENCYCLOPEDIA OF MEDICINE

Lyme disease

Reported number of Lyme disease cases by state
United States, 1996*
18

63
2

0
19

2

396

0

3
2

251

19

5
1

64
0

0
1

36
42

26

52

2814

32

10 32

12 57
66

24
9

27
24 9

97

0

5301

28

1

9
55

HI 1

*n = 16,455

CT 3104
DE 173
DC 3
MD 447
MA 321
NH 47
NJ 534
VT 26

Lyme disease accounts for more than 90% of all reported vector-borne illnesses in the United States. It is caused by an infection
transmitted by the bite of ticks carrying the Borrelia burgdorferi bacterium. (Data taken from the Centers for Disease Control.
Illustration by Electronic Illustrators Group.)

Diagnosis
A clear diagnosis of Lyme disease can be difficult,
and relies on information the patient provides and the
doctor’s clinical judgment, particularly through elimination of other possible causes of the symptoms.
Lyme disease may mimic other conditions, including
chronic fatigue syndrome (CFS), multiple sclerosis
(MS), and other diseases with many symptoms involving multiple body systems. Differential diagnosis
(distinguishing kyme disease from other diseases) is
based on clinical evaluation with laboratory tests
used for clarification when necessary. A two-test
approach is common to confirm the results. Because
of the potential for misleading results (false-positive
and false-negative), laboratory tests alone cannot
establish the diagnosis.
In February 1999 the Food and Drug
Administration (FDA) approved a new blood test for
Lyme disease called PreVue. The test, which searches
for antigens (substances that stimulate the production
GALE ENCYCLOPEDIA OF MEDICINE

of antibodies) produced by Borrelia burgdorferi, gives
results within one hour in the doctor’s office. A positive
result from the PreVue test is confirmed by a second
blood test known as the Western blot, which must be
done in a laboratory.
Doctors generally know which disease-causing
organisms are common in their geographic area. The
most helpful piece of information is whether a tick bite
or rash was noticed and whether it happened locally or
while traveling. Doctors may not consider Lyme disease if it is rare locally, but will take it into account if a
patient mentions vacationing in an area where the
disease is commonly found.

Treatment
The treatment for Lyme disease is antibiotic therapy; however, overprescribing of antibiotics can lead
to serious problems, so the decision to treat must be
made with care. Disease organisms can develop
2283

Lyme disease

resistance to families of medications over time, rendering the drugs useless. Furthermore, testing and treatments can be expensive. If a patient has strong
indications of Lyme disease (symptoms and medical
history), the doctor will probably begin treatment on
the presumption of this disease. The American College
of Physicians recommends treatment for a patient with
a rash resembling EM or who has arthritis, a history of
an EM-type rash, and a previous tick bite.
The benefits of treating early must be weighed
against the risks of over treatment. The longer a
patient is ill with Lyme disease before treatment, the
longer the course of therapy must be, and the more
aggressive the treatment. The development of opportunistic organisms may produce other symptoms. For
example, after long-term antibiotic therapy, patients
can become more susceptible to yeast infections.
Treatment may also be associated with adverse drug
reactions.
For most patients, oral antibiotics (doxycycline or
amoxicillin) are prescribed for 21 days. When symptoms indicate nervous system involvement or a severe
episode of Lyme disease, intravenous antibiotic (ceftriaxone) may be given for 14-30 days. Some physicians consider intravenous ceftriaxone the best
therapy for any late manifestation of disease, but
treatments for late Lyme disease are still controversial
as of 2003. Corticosteroids (oral) may be prescribed if
eye abnormalities occur, but they should not be used
without first consulting an eye doctor.
The doctor may have to adjust the treatment regimen or change medications based on the patient’s
response. Treatment can be difficult because Borrelia
burgdorferi comes in several strains (some may react to
different antibiotics than others) and may even have
the ability to switch forms during the course of infection. Also, Borrelia burgdorferi can shut itself up in cell
niches, allowing it to hide from antibiotics. Finally,
antibiotics can kill Borrelia burgdorferi only while it is
active rather than dormant.

spilanthes (Spilanthes spp.), may be effective in treating diseases like LD that are caused by spirochetes
(spiral-shaped bacteria).

Prognosis
If aggressive antibiotic therapy is given early, and
the patient cooperates fully and sticks to the medication schedule, recovery should be complete. Only a
small percentage of Lyme disease patients fail to
respond or relapse (have recurring episodes). Most
long-term effects of the disease result when diagnosis
and treatment is delayed or missed. Co-infection with
other infectious organisms spread by ticks in the same
areas as Borrelia burgdorferi (babesiosis and ehrlichiosis, for instance) may be responsible for treatment
failures or more severe symptoms. Most fatalities
reported with Lyme disease involved patients coinfected with babesiosis.

Prevention
Update on vaccination
A vaccine for Lyme disease known as LYMErix
was available from 1998 to 2002, when it was removed
from the United States market. The decision was influenced by reports that LYMErix may be responsible
for neurologic complications in vaccinated patients.
Researchers from Cornell-New York Hospital presented a paper at the annual meeting of the
American Neurological Association in October 2002
that identified nine patients with neuropathies linked
to vaccination with LYMErix. In April 2003, the
National Institute of Allergy and Infectious Diseases
(NIAID) awarded a federal grant to researchers at
Yale University School of Medicine to develop a new
vaccine against Lyme disease. As of late 2003, the best
prevention strategy is through minimizing risk of
exposure to ticks and using personal protection
precautions.
Minimizing risk of exposure

Alternative treatment
Supportive therapies may minimize symptoms of
LD or improve the immune response. These include
vitamin and nutritional supplements, mostly for
chronic fatigue and increased susceptibility to infection. For example, yogurt and Lactobacillus acidophilus preparations help fight yeast infections, which are
common in people on long-term antibiotic therapy. In
addition, botanical medicine and homeopathy can be
considered to help bring the body’s systems back to a
state of health and well being. A Western herb,
2284

Precautions to avoid contact with ticks include
moving leaves and brush away from living quarters.
Most important are personal protection techniques
when outdoors, such as:


Spraying tick repellent on clothing and exposed skin.



Wearing light-colored clothing to maximize ability
to see ticks.



Tucking pant legs into socks or boot top.



Checking children and pets frequently for ticks.
GALE ENCYCLOPEDIA OF MEDICINE

Check for ticks, particularly in the area of the groin,
underarm, behind ears, and on the scalp.

Babesiosis—A disease caused by protozoa of the
genus Babesia characterized by a malaria-like
fever, anemia, vomiting, muscle pain, and enlargement of the spleen. Babesiosis, like Lyme disease, is
carried by a tick.



Stay calm and grasp the tick as near to the skin as
possible, using a tweezer.



To minimize the risk of squeezing more bacteria into
the bite, pull straight back steadily and slowly.



Do not try to remove the tick by using petroleum
jelly, alcohol, or a lit match.

Bell’s palsy—Facial paralysis or weakness with a
sudden onset, caused by swelling or inflammation
of the seventh cranial nerve, which controls the
facial muscles. Disseminated Lyme disease sometimes causes Bell’s palsy.
Blood-brain barrier—A blockade of cells separating the circulating blood from elements of the central nervous system (CNS); it acts as a filter,
preventing many substances from entering the central nervous system.
Cerebrospinal fluid—Clear fluid found around the
brain and spinal cord and in the ventricles of the
brain.



Place the tick in a closed container (for species identification later, should symptoms develop) or dispose
of it by flushing.



See a physician for any sort of rash or patchy discoloration that appears three to 30 days after a tick
bite.

Disseminated—Scattered or distributed throughout
the body. Lyme disease that has progressed beyond
the stage of localized EM is said to be disseminated.
Erythema migrans (EM)—A red skin rash that is one
of the first signs of Lyme disease in about 75% of
patients.
Lyme borreliosis—Another name for Lyme disease.
Spirochete—A spiral-shaped bacterium. The bacteria that cause Lyme disease and syphilis, for
example, are spirochetes.
Vector—An animal carrier that transfers an infectious organism from one host to another. The vector
that transmits Lyme disease from wildlife to
humans is the deer tick or black-legged tick.
Zoonosis (plural, zoonoses)—Any disease of animals that can be transmitted to humans under natural conditions. Lyme disease and babesiosis are
examples of zoonoses.

In highly tick-populated areas, each individual
should be inspected at the end of the day to look for
ticks.
Minimizing risk of disease
The two most important factors are removing the
tick quickly and carefully, and seeking a doctor’s evaluation at the first sign of symptoms of Lyme disease.
When in an area that may be tick-populated:
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Bacterial Diseases Caused by Spirochetes: Lyme
Disease (Lyme Borreliosis).’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Edlow, Jonathan A., MD. ‘‘Tick-Borne Diseases, Lyme.’’
eMedicine December 13, 2002. <http://
www.emedicine.com/emerg/topic588.htm>.
Krupp, L. B., L. G. Hyman, R. Grimson, et al. ‘‘Study and
Treatment of Post Lyme Disease (STOP-LD): A
Randomized Double Masked Clinical Trial.’’
Neurology 60 (June 24, 2003): 1923–1930.
Nachman, S. A., and L. Pontrelli. ‘‘Central Nervous System
Lyme Disease.’’ Seminars in Pediatric Infectious
Diseases 14 (April 2003): 123–130.
Pavia, C. S. ‘‘Current and Novel Therapies for Lyme
Disease.’’ Expert Opinion on Investigational Drugs
12 (June 2003): 1003–1016.
Susman, Ed. ‘‘ANA: Neurological Impairment Seen in
Patients Given LYMErix Lyme Disease Vaccine.’’
Doctor’s Guide October 16, 2002. <http://
www.plsgroup.com/dg/220652.htm>.
Wormser, G. P., R. Ramanathan, J. Nowakowski, et al.
‘‘Duration of Antibiotic Therapy for Early Lyme
Disease. A Randomized, Double-Blind, PlaceboControlled Trial.’’ Annals of Internal Medicine 138
(May 6, 2003): 697–704.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
Lyme Disease Foundation. One Financial Plaza, Hartford,
CT, 06103. (800) 886-LYME. <http://
www.lyme.org>.
Lyme Disease Network of NJ, Inc. 43 Winton Road, East
Brunswick, NJ 08816. <http://www.lymenet.org>.
2285

Lyme disease



KEY TERMS

Lymph node biopsy

National Institute of Allergy and Infectious Diseases
(NIAID). 31 Center Drive, Room 7A50 MSC 2520,
Bethesda, MD, 20892. (301) 496-5717. <http://
www.niaid.nih.gov>.
OTHER

Normal lymph glands are no larger than 0.5 in
(1.3 cm) in diameter and are difficult to feel. However,
lymph nodes can enlarge to greater than 2.5 in (6 cm)
and can become sore. Most often the swelling is caused
by an infection, but it can also be caused by cancer.

Centers for Disease Control and Prevention, Division of
Vector-Borne Infectious Diseases. CDC Lyme Disease
Home Page. <http://www.cdc.gov/ncidod/dvbid/
lyme/>.
National Institute of Neurological Disorders and Stroke
(NINDS) Fact Sheet. Bell’s Palsy. Bethesda, MD:
NINDS, 2003.
NINDS Information Page. Neurological Complications of
Lyme Disease. Bethesda, MD: NINDS, 2003.

Cancers can metastasize (spread) through the
lymph system from the site of the original tumor to
distant parts of the body where secondary tumors are
formed. The purpose of a lymph node biopsy is to
determine the cause of the swelling and/or to see if
cancer has begun to spread through the lymph system.
This information is important in staging the cancer
and devising a treatment plan.

Rebecca J. Frey, PhD

Lymph node angiogram see
Lymphangiography

Precautions
Women who are pregnant should inform their
doctor before a lymph node biopsy, although pregnancy will not affect the results.

Description

Lymph node biopsy
Definition
A lymph node biopsy is a procedure in which all or
part of a lymph node is removed and examined to
determine if there is cancer within the node.

Purpose
The lymph system is the body’s primary defense
against infection. It consists of the spleen, tonsils,
thymus, lymph nodes, lymph vessels, and the clear,
slightly yellow fluid called lymph. These components
produce and transport white blood cells called lymphocytes and macrophages that rid the body of infection. The lymph system is also involved in the
production of antibodies. Antibodies are proteins
that fight bacteria, viruses, and other foreign materials
that enter the body.
The lymph vessels are similar to veins, only
instead of carrying blood as veins do, they circulate
lymph to most tissues in the body. Lymph nodes are
about 600 small, bean-shaped collections of tissue
found along the lymph vessel. They produce cells and
proteins that fight infection, and clean and filter
lymph. Lymph nodes are sometimes called lymph
glands, although they are not true glands. When someone talks about having swollen glands, they are actually referring to lymph nodes.
2286

There are three kinds of lymph node biopsy.
Sentinel lymph node mapping and biopsy is a promising new technique that is discussed in its own entry.
Fine needle aspiration (FNA) biopsy, often just called
needle biopsy, is done when the lymph node of interest
is near the surface of the body. A hematologist (a
doctor who specializes in blood diseases) usually performs the test. In FNA biopsy, a needle is inserted
through the skin and into the lymph node, and a
sample of tissue is drawn out of the node. This material is preserved and sent to the laboratory for
examination.
Advantages of a needle biopsy are that the test is
minimally invasive. Only a local anesthetic is used, the
procedure generally takes less than half an hour, and
there is little pain afterwards. The disadvantage is that
cancer may not be detected in the small sample of cells
removed by the needle.
Open lymph node biopsy is a surgical procedure.
It is done by a surgeon under general anesthesia on
lymph nodes in the interior of the body and under local
anesthesia on surface lymph nodes where FNA biopsy
is considered inadequate. Once there is adequate
anesthesia, the surgeon makes a small cut and removes
either the entire lymph node or a slice of tissue that is
then sent to the laboratory for examination. Results in
both kinds of biopsies take one to three days.
Open biopsy can be advantageous in that it is easier
to detect and identify the type of cancer in a large piece
of tissue. Also, lymph nodes deep in the body can be
sampled. Disadvantages include a longer recovery time,
GALE ENCYCLOPEDIA OF MEDICINE

Lymph node biopsy

Lymphocytes

Granuloma

Epithelioid cells

Giant cells

LYMPH NODE
Lymph node biopsy is a procedure in which a sample of lymph node tissue is removed for laboratory analysis. It is generally
performed on an outpatient basis. (Illustration by Electronic Illustrators Group.)

soreness at the biopsy site for several days, and the use
of deeper anesthesia, increasing the risks to the patient.
The procedure is done in a hospital or outpatient surgery center and takes about an hour, with additional
time to recover from general anesthesia.

Risks
There are few risks associated with lymph node
biopsy. The main risks are excessive bleeding (usually
only in people with blood disorders) and allergic reaction to general anesthesia (rare). Occasionally the
biopsy site becomes infected.

Preparation
No particular preparation is necessary for a needle biopsy. For an open biopsy, patients need standard
pre-operative blood tests and other tests to evaluate
general health. The doctor should be informed about
any medications (prescription, non-prescription, or
herbal) the patient is taking, as well as past bleeding
problems or allergies to medication or anesthesia.

Aftercare
Little aftercare is needed in a needle biopsy other
than a bandage to keep the biopsy site clean. Patients
who have general anesthesia for an open biopsy often feel
drowsy and tired for several days following the procedure, and should not plan to drive home after biopsy.
The incision site must be kept clean and dry, and a
follow-up visit to check on healing is usually necessary.
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Normal lymph nodes are small and flat. When
examined under the microscope, they show no signs
of cancer or infection.

Abnormal results
Abnormal lymph nodes are usually enlarged and
contain cancerous (malignant) cells and/or show signs
of infection.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. 800(ACS)-2345).<http://
www.cancer.org>.
2287

Lymphadenitis

Description

KEY TERMS
Lymph nodes—Small, bean-shaped organs located
throughout the lymphatic system. The lymph nodes
store special cells that can trap cancer cells or
bacteria that are traveling through the body in
lymph. Also called lymph glands.
Lymphocytes—Small white blood cells that bear the
major responsibility for carrying out the activities of
the immune system; they number about 1 trillion.
Malignant—Cancerous. Cells tend to reproduce
without normal controls on growth and form
tumors or invade other tissues.
Spleen—An organ located at the left side of the
stomach that acts as a reservoir for blood cells and
produces lymphocytes and other products involved
in fighting infection.
Thymus—An organ near the base of the neck that
produces cells that fight infection. It is at its largest
at puberty, then declines in size and function during adult life.
Tonsils—Small masses of tissue at the back of the
throat.

Cancer Information Service. National Cancer Institute.
Building 31, Room 10A19, 9000 Rockville Pike,
Bethesda, MD 20892. (800)4-CANCER. <http://
www.nci.nih.gov/cancerinfo>.
OTHER

ThriveOnline June 12, 2001. <http://thriveonline.oxygen.com/medical/library/article/003933.html>.

Tish Davidson, A.M.

Lymphadenitis
Definition
Lymphadenitis is the inflammation of a lymph
node. It is often a complication of a bacterial infection
of a wound, although it can also be caused by viruses
or other disease agents. Lymphadenitis may be either
generalized, involving a number of lymph nodes; or
limited to a few nodes in the area of a localized infection. Lymphadenitis is sometimes accompanied by
lymphangitis, which is the inflammation of the lymphatic vessels that connect the lymph nodes.
2288

Lymphadenitis is marked by swollen lymph nodes
that are painful, in most cases, when the doctor
touches them. If the lymphadenitis is related to an
infected wound, the skin over the nodes may be red
and warm to the touch. If the lymphatic vessels are
also infected, there will be red streaks extending
from the wound in the direction of the lymph nodes.
In most cases, the infectious organisms are hemolytic
Streptococci or Staphylococci. Hemolytic means that
the bacteria produce a toxin that destroys red blood
cells.
The extensive network of lymphatic vessels
throughout the body and their relation to the lymph
nodes helps to explain why bacterial infection of the
nodes can spread rapidly to or from other parts of
the body. Lymphadenitis in children often occurs
in the neck area because these lymph nodes are close
to the ears and throat, which are frequent locations of
bacterial infections in children.

Causes and symptoms
Streptococcal and staphylococcal bacteria are the
most common causes of lymphadenitis, although
viruses, protozoa, rickettsiae, fungi, and the tuberculosis bacillus can also infect the lymph nodes. Diseases
or disorders that involve lymph nodes in specific areas
of the body include rabbit fever (tularemia), catscratch disease, lymphogranuloma venereum, chancroid, genital herpes, infected acne, dental abscesses,
and bubonic plague. In children, tonsillitis or bacterial
sore throats are the most common causes of lymphadenitis in the neck area. Diseases that involve lymph
nodes throughout the body include mononucleosis,
cytomegalovirus infection, toxoplasmosis, and
brucellosis.
The early symptoms of lymphadenitis are swelling
of the nodes caused by a buildup of tissue fluid and an
increased number of white blood cells resulting from
the body’s response to the infection. Further developments include fever, often as high as 101-102 8F (3839 8C) together with chills, loss of appetite, heavy
perspiration, a rapid pulse, and general weakness.

Diagnosis
Physical examination
The diagnosis of lymphadenitis is usually based
on a combination of the patient’s history, the external
symptoms, and laboratory cultures. The doctor will
press (palpate) the affected lymph nodes to see if they
GALE ENCYCLOPEDIA OF MEDICINE

Hemolytic—Able to break down or dissolve red
blood cells. The bacteria that cause lymphadenitis
are hemolytic.
Hernia—The bulging of a part of the intestine or
other organ through its surrounding wall of tissue.
Most hernias are in the abdominal cavity. An inguinal hernia is located in the groin area.
Lymph nodes—The glandlike masses of tissue in
the lymphatic system that contain lymphocytes.
The lymph nodes also filter lymph, which is a
clear yellowish tissue fluid that carries lymphocytes
and fats throughout the body.
Lymphangitis—Inflammation of the lymphatic vessels. It often occurs together with lymphadenitis.

Swollen lymph node glands in a young girl’s neck. (Custom
Medical Stock Photo. Reproduced by permission.)

are sore or tender. Swollen nodes without soreness are
often caused by cat-scratch disease. In children, the
doctor will need to rule out mumps, tumors in the neck
region, and congenital cysts that resemble swollen
lymph nodes.
Although lymphadenitis is usually diagnosed in
lymph nodes in the neck, arms, or legs, it can also
occur in lymph nodes in the chest or abdomen. If the
patient has acutely swollen lymph nodes in the groin,
the doctor will need to rule out a hernia in the groin
that has failed to reduce (incarcerated inguinal hernia). Hernias occur in 1% of the general population;
85% of patients with hernias are male.

Septicemia—The presence of bacteria and their
toxins in the bloodstream. Septicemia is sometimes
called blood poisoning.
Staphylococcus—Any of several species of spherical bacteria that occur in groups of four or irregular clusters. Staphylococci frequently cause skin
infections.
Streptococcus—Any of several species of bacteria that are spherical in shape and form pairs or
chains. Streptococci cause scarlet fever, tonsillitis,
and pneumonia, and are often involved in
lymphadenitis.

treated with antibiotics, usually penicillin G
(Pfizerpen, Pentids), nafcillin (Nafcil, Unipen), or
cephalosporins. Erythromycin (Eryc, E-Mycin,
Erythrocin) is given to patients who are allergic to
penicillin.

Laboratory tests
The most significant tests are a white blood cell
count (WBC) and a blood culture to identify the organism. A high proportion of immature white blood cells
indicates a bacterial infection. Blood cultures may be
positive, most often for a species of staphylococcus or
streptococcus. In some cases, the doctor may order a
biopsy of the lymph node.

Treatment
Medications
The medications given for lymphadenitis vary
according to the bacterium or virus that is causing it.
If the patient also has lymphangitis, he or she will be
GALE ENCYCLOPEDIA OF MEDICINE

Supportive care
Supportive care of lymphadenitis includes resting
the affected limb and treating the area with hot moist
compresses.
Surgery
Cellulitis associated with lymphadenitis should
not be treated surgically because of the risk of spreading the infection. Pus is drained only if there is an
abscess and usually after the patient has been started
on antibiotic treatment. In some cases, a biopsy of an
inflamed lymph node is necessary if no diagnosis has
been made and no response to treatment has occurred.
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Lymphadenitis

KEY TERMS

Lymphangiography

Prognosis
The prognosis for recovery is good if the patient is
treated promptly with antibiotics. In most cases, the
infection can be brought under control in three or four
days. Patients with untreated lymphadenitis may develop
blood poisoning (septicemia), which is sometimes fatal.

Prevention
Prevention of lymphadenitis depends on prompt
treatment of bacterial and viral infections.

KEY TERMS
Contrast agent—A substance that makes shadows
on x rays.
Filariasis—A tropical disease caused by worms that
live in lymph channels.
Hodgkin’s disease—A cancer of the lymphatic
system.
Lymphoma—A type of lyphatic cancer.

Resources
BOOKS

McPhee, Stephen, et al., editors. ‘‘Blood Vessels &
Lymphatics.’’ In Current Medical Diagnosis and
Treatment, 1998. 37th ed. Stamford: Appleton & Lange,
1997.

Rebecca J. Frey, PhD

Lymphangiography
Definition
Lymphangiography, or lymph node angiogram, is
a test which utilizes x-ray technology, along with the
injection of a contrast agent, to view lymphatic circulation and lymph nodes for diagnostic purposes.

have spread through lymphatic channels. Swelling,
sometimes massive, can result from blocked lymphatics. The most outstanding example of this is the tropical disease filariasis, which results in the swelling of
the legs termed elephangiasis.
Lymphangiography gives precise information on
the extent and location of lymph vessels and lymph
nodes. Oftentimes, it is performed to evaluate the extent
of a lymphatic cancer. Rarely, it is a tool, which aids
surgeons attempting to reconstruct the lymphatics.

Precautions
Lymphangiography should not be performed on
patients with dye or shellfish allergies or on patients
with chronic lung disease, kidney disease, heart disease, or liver disease.

Description
Purpose
The lymphatic system is a one way circulation that
channels tissue fluid back into the heart. The watery
fluid called lymph seeps out of the blood into tissues,
and while journeying back to the heart, it picks up
germs, cancer cells, and some waste products. Lymph
passes through the lymph nodes, which are major
arsenals of immune defense that attack germs carried
in the lymph. Cancer cells are also subject to attack in
lymph nodes.
Cancers of the lymph system, such as Hodgkin’s
disease and non-Hodgkin’s lymphomas, spread
throughout the body. Treatment often depends upon
finding all the disease and directing radiation to each
location. Planning other kinds of treatment, such as
surgery or chemotherapy, may also require that the full
extent of the disease be known.
The lymphatic circulation may become clogged by
infection, injury, or several other types of cancer that
2290

A lymphangiogram begins by injecting a blue dye
into a hand or foot. The lymph system picks up dye,
which in turn will highlight the lymph vessels. This
process may take a full day. When the lymphatic channel is clearly visible, the radiologist will insert an even
tinier needle into that vessel and inject a contrast agent.
X rays outline the journey of the contrast agent as it
travels to the heart through lymph vessels and nodes.

Preparation
Unless a dye allergy is suspected, no special preparation is need. If an allergy is suspected, a non-ionic
contrast agent can be administered instead.

Aftercare
Prior to suture removal seven to 10 days after the
procedure, the patient should watch for any sign of
infection around the site.
GALE ENCYCLOPEDIA OF MEDICINE

Lipid pneumonia can occur if the contrast agent
penetrates the thoracic duct. An allergic reaction to
the contrast agent is possible, causing a range of symptoms that can range from innocuous to life
threatening.

a characteristic of advanced chronic lymphedema. In
very severe cases, untreated lymphedema may even
result in a rare form of lymphatic cancer called
lymphangiosarcoma.
Lymphedema affects approximately 100 million
people worldwide, including at least 3 million people
in the United States.

Resources

Symptoms of lymphedema include:

BOOKS

Merrill, Vinta. ‘‘Lymphangiography.’’ In Atlas of
Roentgenographic Positions and Standard Radiologic
Procedures. Saint Louis: The C. V. Mosby Co., 1975.



swelling of an affected limb, which may develop
gradually or suddenly



tightness of the skin and a feeling of heaviness in the
affected area



discomfort or a feeling of ‘‘pins and needles’’ in the
affected area



pitting edema, which can be identified by observing a
temporary indentation in the swollen area when pressure is placed on the affected area



aching in the adjacent shoulder or hip due to the
increasing weight of the swelling limb



tight fitting of a ring, wristwatch, or bracelet, without a gain in weight.

J. Ricker Polsdorfer, MD

Lymphedema
Description
Lymphedema involves blockage of the lymph vessels, with a resulting accumulation of lymphatic fluid
in the interstitial tissues of the body. The lymphatic
system consists of lymph vessels and lymph nodes
throughout the body. The lymph vessels collect lymphatic fluid, which consists of protein, water, fats, and
wastes from cells. The lymph vessels transport the
fluid to the lymph nodes, where waste materials and
foreign materials are filtered out from the fluid. The
fluid is then returned to the blood. When the vessels
are damaged or missing, the lymph fluid cannot move
freely throughout the system but accumulates. This
accumulation of fluid results in abnormal swelling of
the arm(s) or leg(s), and occasionally swelling in other
parts of the body.
Lymphedema is a very serious condition. There is
no cure for lymphedema and once it develops, it can be
a long-term, uncomfortable, and sometimes painful
condition requiring daily treatment. When lymphedema is not treated, the protein-rich fluid continues
to accumulate, leading to even more swelling and
hardening (referred to as fibrosis) of the tissues. This
fluid is a good culture medium for bacteria, thus
resulting in reoccurring infections when there are injuries to the skin, decrease or loss of functioning of the
affected limbs, and skin breakdown. Infections,
referred to lymphangitis, can affect the connective
tissue under the skin. Repeated infections may result
in scarring, which in turn makes the tissue susceptible
to more swelling and infection. Over time, these infections result in tissue hardening (i.e., fibrosis), which is
GALE ENCYCLOPEDIA OF MEDICINE

In 90% of the cases, lymphedema is diagnosed
through observations, measurements, and symptoms.
The remaining 10% require the use of more complex diagnostic tests such as lymphoscintigraphy.
Lymphoscintigraphy is a technique in which a radioactive substance that concentrates in the lymphatic
vessels is injected into the affected tissue and is
mapped using a gamma camera, which images the
location of the radioactive tracer. Magnetic resonance
imaging (MRI), computed tomography (CT) scanning, and duplex ultrasound are imaging techniques
that are also sometimes used as diagnostic tools for
lymphedema.
There are three stages of lymphedema:


Stage 1 (spontaneously reversible) - tissue is still at
the pitting stage and soft to the touch. Upon waking
in the morning, the limbs or affected areas are of
normal or almost normal size



Stage 2 (spontaneously irreversible) - tissue is nonpitting and no longer soft to the touch, fibrosis
begins to form, and the limbs increase in size



Stage 3 (lymphostatic elephantiasis) - swelling is irreversible and the affected areas are very swollen. The
skin hardens and begins to break down, fibrosis is
more extensive, and patients may need surgery to
remove some of the swollen tissues.
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Lymphedema

Risks

Lymphedema

Causes
Primary lymphedema is an inherited condition,
where the patient is born without lymph vessels and
nodes. The swelling associated with primary lymphedema usually occurs during adolescence and affects
the foot or calf. A rare form of primary lymphedema,
called Milroy’s Disease, occurs in pregnancy.
However, secondary lymphedema, or acquired lymphedema, develops as a result of an injury to the
lymph system. Specific causes include surgical treatments for certain types of cancers, especially those
cancers that currently require the removal of lymph
nodes. Radiation treatment for cancer or for some
AIDs-related diseases such as Kaposi-Sarcoma may
also result in lymphedema, as radiation may damage
or destroy lymph nodes or cause the formation of scar
tissue that can interrupt the normal flow of the lymphatic fluid. Specific cancers and their treatment that
may result in lymphedema include malignant melanoma, breast (in both women and men), gynecological,
head and neck, prostate, testicular, bladder, and colon
cancer. Other causes of lymphedema include trauma
to the lymphatic system from burns, liposuction, tattooing, injuries, surgery, radiation, obesity, heart or
circulatory
disease,
and
multiple
sclerosis.
Lymphedema in people at risk may not develop the
condition immediately, but develop the condition
weeks, months, or even years later. Aircraft travel
has been linked to the development of lymphedema
in patients after cancer surgery, possible due to the
decreased cabin pressure.
In Western countries, one of the most common
causes of lymphedema is mastectomy with axillary
dissection (removal of the breast and underarm
lymph tissue for treatment of breast cancer), which
may result in lymphedema of the breast, underarm,
or arm on the side of the surgery in 10-20% of
patients. This occurs because the lymphatic drainage
of the arm passes through the axilla (armpit), and
tissue in the axilla is removed during the mastectomy.
To reduce the risk of developing lymphedema after
breast cancer treatment, there is an alternative treatment that avoids axillary lymph node dissection.
Sentinel lymph node biopsy is a new diagnostic procedure used to determine whether the breast cancer has
spread (metastasized) to axillary lymph nodes. A
sentinel lymph node biopsy requires the removal of
only one to three lymph nodes for close review by a
pathologist. If the sentinel nodes do not contain
tumor (cancer) cells, this may eliminate the need to
remove additional lymph nodes in the axillary area.
Early research on this technique indicates that sentinel lymph node biopsy may be associated with less
2292

pain and fewer complications than standard axillary
dissection. Because the procedure is so new, long
term data are not yet available. However, there is
still a risk for developing lymphedema because of
follow-up radiation treatments or chemotherapy,
which may also damage the lymph nodes.
Persons who have developed lymphedema after
cancer treatment should be checked for a possible
reoccurrence of cancer if they experience a sudden
increase of swelling, for the tumor growth may be
responsible for blocking lymphatic flow.

Treatments
Lymphedema is a chronic condition that cannot be
cured, but it can be improved with treatment. There are
several major components of a lymphedema treatment
program, which should be administered by the
health care provider in cooperation with a physical
therapist trained in lymphedema treatment. Complete
Decongestive Therapy (CDT; also referred to as Complex Decongestive Therapy (CDT) or as Complete
Decongestive Physiotherapy (CDP)) combines manual
lymph drainage (MLD) with compression techniques
and with patient education on self-care needs. The goals
of the treatment program are to:


remove the stagnant lymph fluids out of the tissues



reduce and help control swelling



soften fibrotic tissue



improve the overall health of the patient.

However, some lymphedema specialists feel that
lymphedema patients with metastatic cancer should
not be treated with CDT, to prevent the spreading of
the cancer.
MLD was developed in 1932 in Denmark by a
doctor and his wife. It was widely used in Europe
and now is accepted as a therapy for lymphedema
patients in the United States. In MLD a series of
rhythmic, light strokes are made in a specific sequence
along the lymphatic vessels and the adjoining tissues.
These movements remove the lymph fluids from the
tissues and return them to the circulatory system, thus
reducing swelling in the affected area.
Compression techniques include the use of compression garments, compression aids, and compression bandages. These techniques encourage natural
drainage and prevent swelling by supporting tissues
in a way that aids in drainage. Compression garments
are knit, stretch sleeves or stockings. Compression
aids are custom-fitted sleeves, stockings, or pads
made of fabric-covered foam. Bandages are an
GALE ENCYCLOPEDIA OF MEDICINE

Self-care techniques are practiced by the patient
or his or her caregiver at home, between visits to the
therapist. Self-care techniques include self-massage,
skin care to maintain healthy tissue, nutritious diet,
and exercise to increase lymph flow, increase mobility,
and to improve the patient’s general health.
Exposure to extreme heat has the potential to
increase lymphedema swelling, so an affected person
or a person at risk of developing lymphedema should
avoid hot tubs, saunas, and steam rooms.
To keep the affected extremities as healthy as
possible, a person with lymphedema should keep the
swollen areas clean and avoid heavy lifting and pulling
as well as avoid any type of trauma, such as cuts,
bruises, sunburn or other burns, injections, sports injuries, insect bites, or cat scratches. Some doctors and
lymphedema therapists recommend that a person with
lymphedema use a preventative course of antibiotics
when having dental treatment, that is, starting antibiotics several days before the appointment and continuing several days afterwards. A person at risk of
developing lymphedema (for example, a woman who
has been treated for breast cancer) should also observe
the same type of precautions to prevent the development of the condition.
If infections occur, then all treatments for lymphedema should be discontinued while the infection is
present, and the infection treated with antibiotics.
Surgery is sometimes used to remove excess tissue
(‘‘debulking’’) if the swollen limb becomes so large and
heavy as to interfere with movement.
Exercise is important for a person with lymphedema, but only in moderation. If the extremity starts
to ache, the person should lie down and elevate the
swollen limb. Recommended exercises include walking, swimming, light aerobics, bike riding, and yoga.
Persons with lymphedema should wear a lymphedema alert bracelet or necklace for safety during a
medical emergency, explaining the risk of infections.
They may also benefit from counseling and membership in support groups to deal with the psychological
impact of the disease. Sometimes patients with lymphedema will be denied insurance coverage for
GALE ENCYCLOPEDIA OF MEDICINE

treatment; as a result patient advocacy groups in
2005 are attempting to get a law passed through the
U.S. Congress guaranteeing insurance coverage for
lymphedema.
Alternative and complementary therapies
The use of clinical aromatherapy in conjunction
with CDT may improve the quality of life for
persons with lymphedema. Clinical aromatherapy
involves the use of essential oils to improve the
functioning of the immune system, for the immune
system is closely associated with the lymphatic system. Also a massage oil comprised of a blend of
frankincense, grapefruit, hyssop, and lavender,
may be used to soften scarred and fibrotic tissues.
Radiation treatments can cause skin contractures,
which can be helped by massage with a blend of
cajeput, frankincense, hyssop, lavender, sage, and
tea tree. Radiation can also have adverse effects on
the bowel, resulting in poor bowel functioning,
scarring, and activity restrictions. Massaging the
abdomen with a blend of grapefruit, fennel, helichrysum, lavender, myrrh, and sage may improve
intestinal functions. When compression techniques
are used, the underlying skin can be treated with a
blend of bay laurel, chamomile, geranium, helchrysum, lavender, patchouli, and vetiver in a combination of castor oil, safflower oil, and grapeseed
oil as carrier oils. Good skin care is important in
preventing infections. Body oils that contain cajeput, cypress, lavender, marjoram, and rosewood
can be applied after bathing to keep the skin
moist and healthy. Finger nail beds can be a portal
of entry for infections, so can be kept moist with
an essential oil blend of chamomile, geranium,
lavender, lemon, sage, tea tree, and ylang ylang.
Resources
BOOKS

Burt, Jeannie, and White, Gwen. Lymphedema: A Breast
Cancer Patient’s Guide to Prevention and Healing.
Berkeley, CA: Publisher’s Group West, 1999.
French, Ramona Moody. Milady’s Guide to Lymph
Drainage Massage. Clifton Park, NY: Milady
Publishing, 2003.
Kelly, Deborah G. A Primer on Lymphedema. Essex, United
Kingdom: Pearson Education, 2001.
Parker, James N. and Parker, Philip M. . San Diego, CA:
Icon Health Publications, 2004.
PERIODICALS

Heckathorn, Peg. ‘‘Use of Aromatherapy in Lymphedema
Management.’’ Lymph Link. Oct-Dec. 2003, Vol. 15,
No. 4, 6-12
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Lymphedema

effective and flexible means of compression. They
work when the patient is active or is resting and can
easily be adjusted to fit changing limb sizes. However,
the bandage should be a special type of short-stretch
bandage and not the long-stretch bandage that is
commonly known as Ace bandages. Only persons
who are trained in lymphedema therapy should tape
or wrap swollen areas.

Lymphedema

KEY TERMS
Axillary nodes—Lymph nodes found in the armpit
that drain the lymph channels from the breast.
Clinical aromatherapy—Aromatherapy is the therapeutic use of plant-derived, aromatic essential oils to
promote physical and psychological well-being. It is
sometimes used in combination with massage and
other therapeutic techniques as part of a holistic
treatment approach.
Debulking—General term used for surgeries in
which subcutaneous tissue is removed from lymphodemous limb.
Fibrosis—Formation of fibrous tissue as a reaction or
as a repair process; may occur due to treatment and/
or disease. in lymphedema condition known as hardening of the limb with resulting restriction of circulatory flow, increased infection, and weeping sores.
Fibrotic—Pertaining to or characterized by fibrosis.
In dermatological description, ‘‘fibrotic’’ would be
used to describe leathery, bound-down, or thickened, scarred skin.
Interstitial fluid—The fluid between cells in tissues.
Referred to as the liquid subtance of the body.
Interstitial space—The fluid filled areas that surround
the cells of a given tissue; also known as tissue space.
Long-stretch bandages—Specialized bandages, similar to an Ace bandage, that have 100 to 200% stretch.
Low-stretch bandage—Specialized bandages, with
30 to 90% stretch, that are used to obtain the correct
compression during the treatment of lymphedema;
also known as short-stretch bandages.
Lymph—The almost colourless fluid that bathes body
tissues and is found in the lymphatic vessels that drain
the tissues of the fluid that filters across the blood vessel
walls from blood. Lymph carries antibodies and lymphocytes (white blood cells that help fight infection)
that have entered the lymph nodes from the blood.
Lymph nodes—Small bean-shaped organs of the
immune system, distributed widely throughout the

OTHER

Lymph Notes, an online information resource and support
group for those with lymphedema and for the family,
friends, and therapists who care for them. Web site:
<www.lymphnotes.com/index.php>
National Lymphedema Network, Latham Square Building,
Suite 1111, 1611 Telegraph Avenue, Oakland, CA
94612-2138. Telephone: (800) 541-3259. Fax: (510) 2083110. Web site: <www.lymphnet.org>
2294

body and linked by lymphatic vessels. Lymph nodes
are garrisons of B, T, and other immune cells.
Lymph System—When sickness or infection invades
the body, the immune system is the first line of
defense. A big part of that defense is the lymph system.
Lymph is carried through the body by lymph vessels
that have valves and muscles to help move the fluid.
Along the route are lymph nodes that serve as filters
for harmful substances. This network of vessels and
nodes together is called the lymph system.
Lymphatic fluid—The clear fluid found outside the
cells which bathes the tissues. It is collected, filtered,
and transported by the lymphatic system from
around the tissues to the blood circulatory system.
Fluid that collects as a result of lymphedema.
Nail beds—The underlying connective tissue that
nourishes the finger and toenails.
Pitting edema—When a swollen area is pressed, the
pressure leaves an indentation (pit) that takes time to
fill back in.
Sentinel node biopsy—A newer procedure performed in order to determine whether breast
cancer has spread to auxiliary (underarm) lymph
nodes. A blue radioactive tracer and/or blue dye is
injected into the area of the breast tumor. The
lymphatic vessels carry the dye or radioactive
material, to a ‘‘sentinel node’’. This sentinel node
is thought to be the first lymph node receiving fluid
from the tumor and the one most likely to contain
cancer cells if the cancer has spread. Only if the
sentinel node contains cancer cells are more lymph
nodes removed.
Skin contracture—A permanent tightening of the
skin that prevents normal movement of the associated body part and that can cause permanent deformity. A contracture develops when the normally
elastic connective tissues are replaced by inelastic
fibrous tissue. This makes the affected area resistant
to stretching and prevents normal movement.

Lymphedema People. Web site:
<www.lymphedemapeople.com/>
Lymphatic Research Foundation. <http://
www.lymphaticresearch.org>
Lymphedema Awareness Foundation. <http://
www.elymphnotes.com/>

Judith Sims
GALE ENCYCLOPEDIA OF MEDICINE

Lymphocyte typing

Lymphocyte typing
Definition
Lymphocyte typing focuses on identifying the
numbers and relative percentages of lymphocytes in
an individual’s bloodstream. Lymphocytes, primarily
T cells and B cells, are types of white blood cells, the
underlying supports of the immune system in the
bloodstream.

Purpose
Determining the numbers and relative percentages of T cells and B cells provides information on
the state of a person’s immune system. By comparing
these values to normal numbers and percentages, the
presence of disease and the side effects of certain drugs
can be revealed. Lymphocyte typing can also show
whether a person has been exposed to certain poisonous substances.

Description
To do a white blood cell count, a small amount of
blood is drawn from a vein. The total number of white
blood cells is calculated, either through microscopic
examination of a blood smear or by using automated
counting equipment. For a white blood cell count with
differential, 100 white blood cells are counted and the
proportion of each type is calculated. Since T cells and
B cells have similar appearances, a differential can
only give the proportion of lymphocytes in the
blood, not the proportion of specific lymphocyte
types.
For more specific information on B cells and T
cells, it is necessary to divide the blood into its separate components. In this procedure, a tube of blood
is placed in a centrifuge, a piece of equipment that
spins the tube in circles at high speed. The force
generated by the spinning causes the various elements in the bloodstream to settle at different levels
of the tube.
The lymphocytes are extracted from the tube and
treated with special dyes, or stains. Each stain is
equipped with an antibody portion that adheres to a
specific type of lymphocyte, such as a B cell or a T cell.
The stains make the cells visible to an automated
counting machine, called a flow cytometer. Based on
the number of times the machine detects a particular
stain, it can calculate the number of the associated cell
type. This procedure can also be used to classify T cells
and B cells into their subtypes.
GALE ENCYCLOPEDIA OF MEDICINE

A lymphocyte cell. (Photograph by Lester V. Bergman, Corbis
Images. Reproduced by permission.)

KEY TERMS
Immune system—The body’s system of defenses
against infectious diseases.
Lymphocytosis—A condition in which the number
of lymphocytes increases above normal levels.
Lymphopenia—A condition in which the number
of lymphocytes falls below normal levels.
White blood cell—A class of cells in the blood that
form the foundation of the body’s immune system.

Preparation
If possible, a person should avoid eating a heavy
meal within hours of the test or engaging in strenuous
exercise for the 24 hours preceding the blood test.

Normal results
In general, normal levels of white blood cells vary
slightly by age and gender. Normal values are lower in
children under the age of 15 and in young adults
between the ages of 20 and 30. After age 30, men
have slightly higher levels of white blood cells than
women.
Normal adult levels of white blood cells are 4,50011,000 cells per microliter of blood. Lymphocytes
account for approximately 25-45% of the total white
blood cell count; the normal range is 1,000-4,800 lymphocytes per microliter of blood. Of the total
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Lymphocytic choriomeningitis

lymphocytes, 60-80% are T cells and approximately
15% are B cells. (There are two other types of lymphocytes; natural killer and K-type; that constitute a
minor proportion of the total lymphocyte numbers.)

Abnormal results
A higher-than-normal level of lymphocytes is
called lymphocytosis. Lymphocytosis occurs if a person has a viral, bacterial, or other type of infection. It
can also occur with certain blood disorders, such as
leukemia.
Lower-than-normal levels of lymphocytes is
called lymphopenia. Lymphopenia can be an indicator
of certain cancers, bone marrow failure, or immune
system deficiency. Medical treatments, such as chemotherapy and radiation therapy, can also deplete the
body’s supply of lymphocytes, as can exposure to
poisonous substances.
Resources
BOOKS

Corbett, Jane Vincent. Laboratory Tests & Diagnostic
Procedures with Nursing Diagnoses. 4th ed. Stamford:
Appleton & Lange, 1996.
Turgeon, Mary Louise. Immunology & Serology in
Laboratory Medicine. St. Louis: Mosby-Year Book,
Inc., 1996.

Julia Barrett

Lymphocytic choriomeningitis
Definition
Lymphocytic choriomeningitis (LCM) is a viral
infection of the membranes surrounding the brain
and spinal cord and of the cerebrospinal fluid.

Description
Lymphocytic choriomeningitis virus infection is
relatively rare and recovery usually occurs spontaneously within a couple of weeks. Many cases are
probably not even identified because the symptoms
range from extremely mild to those resembling severe
flu. A few patients develop symptoms of meningitis. In
some rare cases, the LCM viral infection can spread
throughout the central nervous system, and may even
be fatal.
2296

KEY TERMS
Prodrome—Symptom(s) experienced prior to the
onset of a disease. For example, visual disturbances
may precede and signal the onset of a migraine
headache.

Causes and symptoms
LCM is caused by an arenavirus, which is an
RNA virus and is a mild cousin in the family containing the much more threatening arenaviruses that cause
hemmorrhagic fever. Humans acquire LCM virus
from infected rodents by coming in contact with the
animals or their excretions. Exposure to the virus is
not as unlikely to occur as it seems, because the viral
hosts can be common house mice and even pets, such
as hamsters and chinchillas. Most cases of LCM occur
in fall and winter, when mice seek warmth inside
dwellings. Food and dust can become contaminated
by the excretions of rodents infected with LCM virus.
In 1997, French scientists alerted physicians to suspect
LCM viral infection in people who had contact with
Syrian hamsters.
The symptoms of LCM occur in two phases.
The first (prodrome) stage can produce fever,
chills, muscle aches, cough, and vomiting. In the
second phase, characteristic meningitis symptoms
of headache, stiff neck, listlessness, and nausea and
vomiting may occur. In adults, complications are
rare and recovery may even occur before the
second phase.
The virus is not spread from person to person,
except through pregnancy. LCM virus is one of the
few viruses that can cross the placenta from mother to
child during pregnancy and may be an underrecognized cause of congenital infection in newborns.
Infection with cytomegalovirus, Toxoplasma gondii,
or LCM virus can appear similar enough in infants
to be confused when diagnosed. In cases that have
been recognized among infants, LCM viral infection
has a high mortality rate (about one-third of the babies
studied died).

Diagnosis
LCM can be distinguished from bacterial meningitis by the history of prodrome symptoms and the
period of time before meningitis symptoms begin,
which is about 15-21 days for LCM.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

No antiviral agents exist for LCM virus.
Treatment consists of supporting the patient and
treating the symptoms until the infection subsides,
generally within a few weeks.

B lymphocyte—A type of lymphocyte that circulates in the blood and lymph and produces antibodies when it encounters specific antigens. B
lymphocytes are also called B cells.
Lymph—A clear yellowish fluid circulated by the
lymphatic system. The lymph carries mostly lymphocytes and fats.
Lymphocyte—A specific type of white blood cell
that is important in the production of antibodies.

Jill S. Lasker

Lymphocytic leukemia, acute see
Leukemias, acute
Lymphocytic leukemia, chronic see
Leukemias, chronic

Lymphocytopenia



Leukemia



Side effects of prescription medications



Malnutrition. Diets that are low in protein and overall calorie intake may cause lymphocytopenia.



Radiation therapy



High stress levels



Trauma.

Definition
Lymphocytopenia is a condition marked by an
abnormally low level of lymphocytes in the blood.
Lymphocytes are a specific type of white blood cell
with important functions in the immune system.

Description
Lymphocytes normally account for 15–40% of all
white cells in the bloodstream. They help to protect the
body from infections caused by viruses or fungi. They
also coordinate the activities of other cells in the
immune system. In addition, lymphocytes fight cancer
and develop into antibody-producing cells that
neutralize the effect of foreign substances in the blood.
Lymphocytopenia is the result of abnormalities in
the way lymphocytes are produced, make their way
through the bloodstream, or are lost or destroyed.
These conditions can result from congenital or druginduced decreases in the body’s ability to recognize
and attack invaders.

Causes and symptoms
Lymphocytopenia has a wide range of possible
causes:


AIDS and other viral, bacterial, and fungal infections



Chronic failure of the right ventricle of the heart.
This chamber of the heart pumps blood to the lungs.



Hodgkin’s disease and cancers of the lymphatic system



A leak or rupture in the thoracic duct. The thoracic
duct removes lymphatic fluid from the legs and
abdomen.

GALE ENCYCLOPEDIA OF MEDICINE

The symptoms of lymphocytopenia vary.
Lymphocytes constitute only a fraction of the
body’s white blood cells, and a decline in their
number may not produce any symptoms. A patient
who has lymphocytopenia may have symptoms of the
condition responsible for the depressed level of
lymphocytes.

Diagnosis
Lymphocytopenia is most often detected when
blood tests are performed to diagnose other diseases.

Treatment
Treatment for lymphocytopenia is designed to
identify and correct the underlying cause of the
condition.
Drug-depressed lymphocyte levels usually return
to normal a few days after the patient stops taking the
medication.
A deficiency of B lymphocytes, which mature
into antibody-producing plasma cells, can result in
abnormally low lymphocyte levels. When the number
of B lymphocytes is low, the patient may be treated
with antibiotics, antifungal medications, antiviral
agents, or a substance containing a high concentration
of antibodies (gamma globulin) to prevent infection.
2297

Lymphocytopenia

Treatment

Lymphogranuloma venereum

It is not usually possible to restore normal lymphocyte levels in AIDS patients. Drugs like AZT (azidothymidine, sold under the trade name Retrovir) can
increase the number of helper T cells, which help other
cells wipe out disease organisms.

Prognosis
Very low levels of lymphocytes make patients
vulnerable to life-threatening infection. Researchers
are studying the effectiveness of transplanting bone
marrow and other cells to restore normal lymphocyte
levels. Gene therapy, which uses the body’s own
resources or artificial substances to counter diseases
or disorders, is also being evaluated as a treatment for
lymphocytopenia.
Resources
BOOKS

Berktow, Robert, et al., editors. Merck Manual of Medical
Information: Home Edition. Whitehouse Station, NJ:
Merck Research Laboratories, 1997.

Maureen Haggerty

Lymphogranuloma venereum
Definition
Lymphogranuloma venereum (LGV) is a sexually
transmitted systemic disease (STD) caused by a parasitic organism closely related to certain types of bacteria. It affects the lymph nodes and rectal area, as well
as the genitals, in humans. The name comes from two
Latin words that mean a swelling of granulation tissue
in the lymph nodes resulting from sexual intercourse.
Granulation tissue is tissue that forms during wound
or ulcer healing that has a rough or lumpy surface.

Description
Although LGV is easily treated in its early stages,
it can produce serious complications in its later stages.
LGV is most likely to occur among people living in
tropical or subtropical countries and among military
personnel or tourists in countries or large cities with
high rates of the disease. Prostitutes play a major role
in carrying and transmitting LGV, as was documented
during an outbreak in Florida in the late 1980s. There
are about 1000 documented cases of LGV in the
United States in an average year.
2298

Causes and symptoms
LGV is caused by Chlamydia trachomatis, a globeshaped parasitic organism that reproduces only inside
of living cells. C. trachomatis has 17 subtypes and is
responsible for a wide range of infections in both men
and women; however, only subtypes L1, L2, and L3
cause lymphogranuloma venereum. The parasite has a
two-part lifecycle. In the first stage, it is inert and can
survive outside of cells. In its second stage, it lacks a
cell wall and actively reproduces after gaining entry to
a cell. As the chlamydia organism reproduces inside the
cell, it pushes the nucleus aside and forms an inclusion
that can be identified with tissue staining. LGV differs
from other diseases caused by C. trachomatis in that it
affects the body’s lymphatic system and not just the
moist tissues of the genital region. In humans, the
chlamydia organism is transmitted through vaginal or
anal intercourse, oral sex, or contact with fluid from
open ulcers or infected tissues.
Lymphogranuloma venereum has three stages. In
its primary stage, the disease is more likely to be
detected in men; it may go unnoticed in women.
After an incubation period of four to 30 days, a
small painless ulcer or blister develops in the genital
area. Second-stage LGV develops between one and six
weeks later. In this stage, the infection spreads to the
lymphatic system, forming buboes (swellings) in the
lymph nodes of the groin area. The buboes often
merge, soften, and rupture, forming sinuses and fistulas (hollow passages and ducts) that carry an infectious bloody discharge to the outside of the body.
Patients with second-stage LGV may also have fever,
nausea, headaches, pains in their joints, skin rashes,
and enlargement of the spleen or liver. Third-stage
LGV, which is sometimes called anogenitorectal
syndrome, develops in about 25% of patients. In
men, this stage is usually seen in homosexuals. Thirdstage LGV is marked by rectal pain, constipation, a
discharge containing pus or bloody mucus, and the
development of strictures (narrowing or tightening of
a body passage) in the rectum or vagina.
LGV can have a number of serious complications.
C. trachomatis infections of any subtype are associated
with long-term fertility problems in women. Strictures
in the rectum can completely close off the lower bowel,
producing eventual rupture of the bowel and inflammation of the abdominal cavity. The patient can
develop chronic abscesses or fistulae in the anal area
or in the vagina in women. Long-term blockages in the
lymph nodes can produce elephantiasis, a condition in
which the patient’s upper legs and groin area become
greatly enlarged. Patients with chronic LGV infection
GALE ENCYCLOPEDIA OF MEDICINE

Anogenitorectal syndrome—Another name for
third-stage LGV.
Aspiration—A procedure in which pus or other
fluid is removed from a body cavity through a
hollow needle connected to a syringe.
Bubo—An inflamed swelling inside a lymph node,
characteristic of second-stage LGV.
Elephantiasis—Abnormal enlargement of the legs
and groin area caused by blockage of the lymphatic
system, as a complication of LGV.
Fistula—A passageway formed by a disease or
injury that drains fluid from an infected area to the
outside or to other parts of the body.

This man suffers from lymphogranuloma venereum, a venereal disease that is caused by the bacterium Chlamydia trachomatis. (Photograph by Milton Reisch, M.D., Corbis Images.
Reproduced by permission.)

have a higher risk of developing cancer in the inflamed
areas.
Chronic LGV can be reactivated in patients who
become infected with the AIDS virus. These patients
develop open ulcers in the groin that are difficult to
treat.

Diagnosis
The diagnosis of LGV is usually made on the basis
of the patient’s history, careful examination of the
genital area and lymph nodes, and blood tests or
cultures to confirm the diagnosis. In the early stages
of the disease, the doctor will need to distinguish
between LGV and such other STDs as syphilis and
herpes. If the patient has developed buboes, the doctor
will need to rule out tuberculosis, cat-scratch disease,
bubonic plague, or tularemia (a disease similar to
plague that is carried by rabbits and squirrels). If the
patient has developed rectal strictures, the doctor will
need to rule out tumors or colitis.
There are several blood tests that can be used to
confirm the diagnosis of LGV. The most commonly
used are the complement fixation (CF) test and the
microimmunofluorescence (micro-IF) tests. Although
the micro-IF test is considered more sensitive than the
CF test, it is less widely available. An antibody titer
(concentration) of 1:64 or greater on the CF test or
GALE ENCYCLOPEDIA OF MEDICINE

Lymph—A clear yellowish fluid that circulates
throughout the body, carrying white blood cells and
fats. The system that produces and circulates lymph is
called the lymphatic system; it includes lymph vessels, lymph nodes, the thymus gland, and the spleen.
Proctitis—Inflammation of the anus and rectum.
Stricture—An abnormal narrowing or tightening of
a body passage. LGV can cause strictures to form in
the patient’s rectum, or in the vagina of female
patients.

1:512 or greater on the micro-IF test is needed to make
the diagnosis of LGV. In some cases, the diagnosis can
be made from culturing C. trachomatis taken from
samples of tissue fluid from ulcers or buboes, or
from a tissue sample from the patient’s rectum.

Treatment
LGV is treated with oral antibiotics, usually tetracycline or doxycycline for 10-20 days, or erythromycin
or trimethoprim sulfamethoxazole for 14 days.
Pregnant women are usually treated with erythromycin rather than the tetracyclines, because this class of
medications can harm the fetus.
Patients who have developed second- and thirdstage complications may need surgical treatment. The
doctor can treat buboes by withdrawing fluid from
them through a hollow needle into a suction syringe.
This procedure is called aspiration. Fistulas and
abscesses also can be treated surgically. Patients who
develop elephantiasis are usually treated by plastic
surgeons. Patients with rectal strictures may need
surgery to prevent bowel obstruction and rupture
into the abdomen.
2299

Lymphogranuloma venereum

KEY TERMS

Lysergic acid diethylamide (LSD)

Prognosis
The prognosis for recovery for most patients is
good, with the exception of AIDS patients. Prompt
treatment of the early stages of LGV is essential to
prevent transmission of the disease as well as fertility
problems and other serious complications of the later
stages.

Purpose
In the United States, LSD has no accepted medical use and its manufacture is illegal.

Description

Prevention
Prevention of lymphogranuloma venereum has
four important aspects:


Avoidance of casual sexual contacts, particularly with
prostitutes, in countries with high rates of the disease.



Observance of proper safeguards by health professionals. Doctors and other healthcare workers
should wear gloves when touching infected areas of
the patient’s body or handling soiled dressings and
other contaminated items. All contaminated materials and instruments should be double-bagged before
disposing.



Tracing and examination of an infected person’s
recent sexual contacts.



Monitoring the patient for recurring symptoms for a
period of six months after antibiotic treatment.

Resources
BOOKS

Chambers, Henry F. ‘‘Infectious Diseases: Bacterial &
Chlamydial.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Lymphomas see Hodgkin’s disease
Lymphopenia see Lymphocytopenia
Lymphosarcomas see Malignant lymphomas

Lysergic acid diethylamide
(LSD)
Definition
Lysergic acid diethylamide (LSD), also known as
‘‘acid,’’ belongs to a class of drugs known as hallucinogens, which distort perceptions of reality. LSD is
the most potent mood- and perception-altering drug
2300

known: doses as small as 30 micrograms can produce
effects lasting six to 12 hours.

LSD is produced synthetically from a fungus that
grows on rye grass. This odorless, colorless, and slightly
bitter-tasting chemical is generally ingested orally and
absorbed from the gastrointestinal system. Manufacturers commonly distribute LSD in small squares of
absorbent paper soaked with the drug, which users
chew and swallow. Use of LSD and other hallucinogens
by secondary school students has decreased since 1998,
but has increased among older teens and young adults
attending dance clubs and all-night raves, according to
the National Institute on Drug Abuse.
LSD alters perceptions by disrupting the action
of the neurotransmitter serotonin, although precisely how it does this is unclear. Studies suggest
LSD acts on certain groups of serotonin receptors,
and that its effects are most prominent in two brain
regions: the cerebral cortex and the locus ceruleus.
The cerebral cortex is involved in mood and perception, and the locus ceruleus receives sensory
signals from all areas of the body. Natural hallucinogens resembling LSD, such as mescaline and
psilocybin, have been used in social and religious
rituals for thousands of years.
After its discovery in 1938, LSD was used experimentally to treat neuroses, narcotic addiction, autism,
alcoholism, and terminally ill cancer patients, and to
study the mechanisms of psychotic diseases like
schizophrenia. Nearly 30 years after its discovery,
manufacture, possession, sale, and use of LSD was
restricted in the United States under the Drug Abuse
Control Amendment of 1965.
LSD’s effects generally begin within an hour of
taking the drug and last for up to 12 hours. The drug is
absorbed from the gastrointestinal tract, and circulated throughout the body and to the brain. It is
metabolized in the liver and excreted in the urine
about 24 hours after ingestion. Physical effects of
LSD may include loss of appetite, sleeplessness, pupil
dilation, dry mouth, salivation, palpitations, perspiration, nausea, dizziness, blurred vision, and anxiety, as
well as increased body temperature, heartbeat, blood
pressure, and blood sugar.
GALE ENCYCLOPEDIA OF MEDICINE

Acid—Common street name for LSD.
Cerebral cortex—Brain region responsible for reasoning, mood, and perception.
Hallucinogen—A drug that distorts sensory perceptions and disturbs emotion, judgment, and
memory.
Hallucinogen persisting perception disorder
(HPPD)—The recurrence of LSD effects after the
drug experience has ended.
Locus ceruleus—Brain region that processes sensory signals from all areas of the body.
Neurotransmitter—Chemical compound in the
brain that transmits signals from one nerve cell to
another.
Serotonin—A neurotransmitter that modulates
the actions of other neurotransmitters in the
brain.
LSD on blotter paper. (Custom Medical Stoch Photo Inc.
Reproduced by permission)

Side Effects
The major effects of LSD are emotional and
sensory. Emotions may shift instantaneously from
euphoria to confusion and despair, and users may
feel as if they are experiencing several emotions
simultaneously. Colors, smells, and sounds may be
highly intensified, and time may appear to move very
slowly. Sensory perceptions may blend in a phenomenon known as synesthesia, in which a person sees
sounds, or smells colors, for example. Users may
have out-of-body sensations, or may perceive their
body has changed shape or merged with another
person or object.

Precautions
Unlike cocaine, amphetamines, heroin, alcohol,
and nicotine, LSD is not considered addictive, but it
is considered dangerous; users are at risk for several
short- and long-term side effects. LSD’s effects are
unpredictable and may vary with the amount ingested
and the user’s personality, mood, expectations, and
surroundings. Users may experience enjoyable sensations on some ‘‘trips,’’ and terrifying feelings of anxiety and despair on others. Most LSD-related deaths
stem not from the LSD’s physical effects on the body,
but from the panicked reactions ensuing from intense
LSD-triggered illusions.
GALE ENCYCLOPEDIA OF MEDICINE

Two long-term effects are associated with LSD
use: psychosis, and hallucinogen persisting perception disorder (HPPD), also known as ‘‘flashbacks.’’
The exact causes of these effects, including the
mechanism by which LSD may cause them, is
unknown. Chronic hallucinogen users or individuals
with underlying personality problems are most vulnerable to these effects, but individuals with no history of psychological disorders have also experienced
them. LSD-induced psychosis may include dramatic
mood swings, loss of cognitive and communication
skills, and hallucinations. Flashbacks generally
involve seeing bright flashes, or halos or trails
attached to moving objects after the LSD ‘‘trip’’ has
ended. Flashbacks can last a few seconds or even
several hours.
According to the Drug Abuse Warning Network
(DAWN), the number of LSD-related hospital emergencies is low compared to those related to cocaine,
heroin, marijuana, methamphetamine, and other illicit drugs. One reason for this trend may be that LSD
currently sold on the black market is less potent than
in the past. LSD dose strengths tend to range from 20
to 80 micrograms today, compared to 100 to 200
micrograms reported during the 1960s and early
1970s.
2301

Lysergic acid diethylamide (LSD)

KEY TERMS

Lysergic acid diethylamide (LSD)

Interactions
LSD flashbacks can be spurred by use of drugs
such as marijuana. Preliminary evidence suggests
serotonin reuptake inhibitors like Prozac and
Zoloft may also exacerbate the LSD flashback
syndrome.
Resources
PERIODICALS

Aghajanian, G. K. and G. J. Marek. ‘‘Serotonin and
Hallucinogens.’’ Neuropsychopharmacology 1999:
16S-23S

2302

ORGANIZATIONS

National Clearinghouse for Alcohol and Drug Information.
11426 Rockville Pike, Suite 200, Rockville, MD. 20852.
(800) 729-6686. <http:\\www.health.org>.
National Institute on Drug Abuse. P.O. Box 30652,
Bethesda, MD. 20824-0652. (888) 644-6432.
<http:\\www.drugabuse.gov>.
U.S. Department of Justice, Drug Enforcement
Administration. 2401 Jefferson Davis Highway,
Alexandria, VA 22301. (888) 644-6432.
<http:\\www.usdoj.gov/dea>.

Ann Quigley

GALE ENCYCLOPEDIA OF MEDICINE

M

Macular degeneration
Definition
Macular degeneration is the progressive deterioration of a critical region of the retina called the
macula. The macula is a 3-5 mm area in the retina that
is responsible for central vision. This disorder leads to
irreversible loss of central vision, although peripheral
vision is retained. In the early stages, vision may be
gray, hazy, or distorted.

central blind spot develops. The wet type progresses
more rapidly and vision loss is more pronounced.
Treatments are available for some, but not most,
cases of the wet form.
Other less common forms of macular degeneration include:


Cystoid macular degeneration. Loss of vision in the
macula due to fluid-filled areas (cysts) in the macular
region. This may be a result of other disorders, such
as aging, inflammation, or high myopia.



Diabetic macular degeneration. Deterioration of the
macula due to diabetes.



Senile disciform degeneration (also known as KuhntJunius macular degeneration). A specific and severe
type of the wet form of ARMD that involves leaking
blood vessels (hemorrhaging) in the macular region.
It usually occurs in people over 40 years old.

Description
Macular degeneration is the most common cause
of legal blindness in people over 60, and accounts for
approximately 11.7% of blindness in the United
States. About 28% of the population over age 74 is
affected by this disease.
Age-related macular degeneration (ARMD) is the
most common form of macular degeneration. It is also
known as age-related maculopathy (ARM), aged
macular degeneration, and senile macular degeneration. Approximately 10 million Americans have some
vision loss that is due to ARMD.
ARMD is subdivided into a dry (atrophic) and a
wet (exudative) form. The dry form is more common
and accounts for 70-90% of cases of ARMD. It progresses more slowly than the wet form and vision loss
is less severe. In the dry form, the macula thins over
time as part of the aging process and the pigmented
retinal epithelium (a dark-colored cell layer at the back
of the eye) is gradually lost. Words may appear
blurred or hazy and colors may appear dim or gray.
In the wet form of ARMD, new blood vessels
grow underneath the retina and distort the retina.
These blood vessels can leak, causing scar tissue to
form on the retina. The wet form may cause visual
distortion and make straight lines appear wavy. A
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Age-related macular degeneration is part of the
aging process. There may be a hereditary component.
Having a family member with ARMD increases a
person’s risk for developing it. There is a slightly
higher incidence in females. Whites and Asians are
more susceptible to developing ARMD than blacks,
in whom the disorder is rare.
ARMD is thought to be caused by hardening and
blocking of the arteries (arteriosclerosis) in the blood
vessels supplying the retina. Some of the same things
that are bad for the heart are thought to contribute to
the development of macular degeneration. These risk
factors include smoking and a diet that is rich in saturated fat. Smokers have a risk of developing ARMD
that is approximately 2.4-3 times that of non-smokers.
Smoking increases the risk of developing wet-type
ARMD, and may increase the risk of developing drytype as well. Dietary fat also increase the risk. In one
2303

Macular degeneration

study of older (age 45-84) Americans, signs of early
ARMD were 80% more common in the group who ate
the most saturated fat compared to those who ate the
least. Low consumption of antioxidants, such as foods
rich in vitamin A, is associated with a higher risk for
developing ARMD. Consumption of moderate
amounts of red wine and foods rich in vitamin A is
associated with a lower risk. It is generally believed
that exposure to ultraviolet (UV) light may contribute
to disease development, but this has not been proven.
The main symptom of macular degeneration is a
change in central vision. The patient may notice
blurred central vision or a blank spot on the page
when reading. The patient may notice visual distortion
such as bending of straight lines. Images may appear
smaller. Some patients notice a change in color perception and some experience abnormal light sensations.
These symptoms may come on suddenly and become
progressively more troublesome. Sudden onset of
symptoms, particularly vision distortion, is an indication for immediate evaluation by an ophthalmologist.

Diagnosis
To make the diagnosis of macular degeneration,
the doctor dilates the pupil with eye drops and examines the interior of the eye, looking at the retina for the
presence of yellow bumps called drusen and for gross
changes in the macula such as thinning. The doctor
also administers a visual field test, looking for blank
spots in the central vision. The doctor may call for
fluorescein angiography (intravenous injection of
fluorescent dye followed by visual examination and
photography of the back of the eye) to determine if
blood vessels in the retina are leaking.
A central visual field test called an Amsler grid is
usually given to patients who are suspected of having
ARMD. It is a grid printed on a sheet of paper (so it is
easy to take home). When looking at a central dot on
the page, the patient should call the doctor right away
if any of the lines appear to be wavy or missing. This
may be an indication of fluid and the onset of wet
ARMD. Patients may also be asked to come in for
more frequent checkups.

Treatment
While loss of vision cannot be reversed, early
detection is important because treatments are available that may halt or slow the progression of the wet
form of ARMD. Treatment for the dry form is not
available as of 1998, but cell transplantation studies
are under study.
2304

A slit-lamp view showing macular degeneration of the eye.
(Custom Medical Stock Photo. Reproduced by permission.)

In wet-type ARMD and in senile disciform macular degeneration, new capillaries grow in the macular
region and leak. This leaking of blood and fluid causes
a portion of the retina to detach. Blood vessel growth,
called neovascularization, can be treated with laser
photocoagulation in some cases, depending upon the
location and extent of the growth. Argon or krypton
lasers can destroy the new tissue and flatten the retina.
This treatment is effective in about half the cases but
results may be temporary. A concern with laser therapy is that the laser also destroys the photoreceptors in
the treated area. If the blood vessels have grown into
the fovea (a region of the macula responsible for fine
vision), treatment may not be possible. Because capillaries can grow very quickly, this form of macular
degeneration should be handled as an emergency and
treated quickly. Patients who are experiencing visual
distortion should seek help immediately.
Another form of treatment for the wet form of
ARMD is radiation therapy with either x rays or a
proton beam. Blood vessels that are proliferating
(growing) are sensitive to treatment with low doses
of ionizing radiation. Nerve cells in the retina are not
growing and are insensitive, so they are not harmed by
this treatment. External beam radiation treatment has
GALE ENCYCLOPEDIA OF MEDICINE

Other therapies that are under study include treatment with alpha-interferon, thalidomide, and other
drugs that slow the growth of blood vessels.
Subretinal surgery also has shown promise in rapidonset cases of wet ARMD. This surgery carries the
risk of retinal detachment, hemorrhage, and acceleration of cataract formation. Other experimental treatments include photodynamic therapy (PDT). For this
treatment, a photosensitizing dye is injected, followed
by irradiation of the area of new blood vessel growth
with a special, low-intensity diode laser. This treatment damages the cells in the blood vessel walls and
causes them to stop growing.
A controversial treatment called rheotherapy
involves pumping the patient’s blood through a device
that removes some proteins and fats. As of 1998, this
had not been proven to be safe or effective.

Alternative treatment
Consumption of a diet rich in antioxidants (beta
carotene and the mixed carotenoids that are precursors of vitamin A, vitamins C and E, selenium, and
zinc), or taking antioxidant nutritional supplements,
may help prevent macular degeneration, particularly
if started early in life. Good dietary sources of antioxidants include citrus fruits, cauliflower, broccoli, nuts,
seeds, orange and yellow vegetables, cherries, blackberries, and blueberries. Research has shown that
nutritional therapy can prevent ARMD or slow its
progression once established. Some doctors recommend taking beta carotene and zinc as a precautionary
measure. Some vitamins are marketed specifically for
the eyes.

Prognosis
The dry form of ARMD is self-limiting and eventually stabilizes. The loss of vision is permanent. The
vision of patients with the wet form of ARMD often
stabilizes or improves even without treatment, at least
temporarily. However, after a few years, patients with
the wet form of ARMD are usually left with only
coarse peripheral vision remaining.
Many patients with macular degeneration lose
their central vision permanently and may become
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Drusen—Tiny yellow dots on the retina that can be
soft or hard and that usually do not interfere with
vision.
Fovea—A tiny pit in the macula that is responsible
for sharp vision.
Neovascularization—Growth of new capillaries.
Photoreceptors—Specialized nerve cells (rods and
cones) in the retina that are responsible for vision.
Retina—The light-sensitive membrane at the back
of the eye that images are focused on. The retina
sends the images to the brain via the optic nerve.

legally blind. However, macular degeneration rarely
causes total loss of vision. Peripheral vision is retained.
The patient can compensate, to some extent, for the
loss of central vision, even though macular degeneration may render them legally blind. Improved lighting
and special low-vision aids may help even if sharpness
of vision (visual acuity) is poor. Vision aids include
special magnifiers that allow the patient to read and
telescopic aids for long-distance vision. The use of
these visual aids plus the retained peripheral vision
usually allow the patient to remain independent.
Registration as a legally blind person will enable a
patient to obtain special services and considerations.

Prevention
Avoiding the risk factors for macular degeneration may help prevent it. This includes avoiding
tobacco smoke and eating a diet low in saturated fat.
Some other behaviors that may help reduce the risk of
wet-type ARMD are eating a diet rich in green, leafy
vegetables and yellow vegetables such as carrots, sweet
potatoes, and winter squash; drinking moderate
amounts of alcohol, such as one or two glasses of red
wine a day; and taking an antioxidant vitamin supplement, especially vitamin A. Some vitamins may be
toxic in large doses, so patients should speak with
their doctors. Vitamins C and E have not been
shown to reduce risk, nor did selenium in one large
study. The use of zinc is controversial: some studies
showed a benefit, others showed no benefit, and one
actually showed an increased risk of ARMD with
increased levels of zinc in the blood. Some doctors
suggest that wearing UV-blocking sunglasses reduces
risk. Use of estrogen in postmenopausal women is
associated with a lower risk of developing ARMD.
2305

Macular degeneration

shown promising results at slowing progression in
limited, early trials. An alternative treatment is internal beam radiation therapy. For this treatment, the
patient is given a local anesthetic and an applicator
containing strontium 90 is inserted into the affected
eye. This brief and localized radiation therapy prevents the growth of blood vessels.

Magnesium imbalance

Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://
www.preventblindness.org>.

Louann W. Murray, PhD

Macule see Skin lesions
Mad cow disease see Creutzfeldt-Jakob
disease
Madura foot see Mycetoma
Maduromycosis see Mycetoma
Magnesium hydroxide see Antacids

Magnesium imbalance
Definition
A mineral found in the fluid that surrounds cells,
magnesium (Mg) is an essential component of more
than 300 enzymes that regulate many body functions.
Imbalances occur when the blood contains more or
less magnesium than it should.

Description
Magnesium is necessary for the formation and
functioning of healthy bones, teeth, muscles, and
nerves. It converts food into energy, builds proteins,
and is instrumental in maintaining adequate levels of
calcium in the blood. Magnesium helps prevent cardiovascular disease and irregular heartbeat, reduces the
risk of bone loss (osteoporosis), and increases an individual’s chance of surviving a heart attack. It may also
help prevent stroke and lessen the effects of existing
osteoporosis.
Fish, dairy products, leafy green vegetables,
legumes, nuts, seeds, and grains are especially good
sources of magnesium, but varying amounts of this
mineral are found in all foods. Some is stored in the
kidneys, and excess amounts are excreted in the urine
or stools.
2306

Magnesium deficiency (hypomagnesemia) or
excess (hypermagnesemia) is rare, but either condition
can be serious.

Causes and symptoms
Hypomagnesemia
Magnesium deficiency most often occurs in people who have been fed intravenously for a long time,
whose diet does not contain enough magnesium, or
who are unable to absorb and excrete the mineral
properly.
Secreting too much aldosterone (the hormone
that regulates the body’s salt-fluid balance), ADH (a
hormone that inhibits urine production), or thyroid
hormone can cause hypomagnesemia.
Other factors associated with hypomagnesemia
include:


Loss of body fluids as a result of stomach suctioning
or chronic diarrhea



Cisplatin (a chemotherapy drug)



Long-term diuretic therapy



Hypercalcemia (abnormally high levels of calcium in
the blood)



Diabetic acidosis (a condition in which the body’s
tissues have a higher-than-normal acid content)



Complications of bowel surgery



Chronic alcoholism



Malnutrition



Starvation



Severe dehydration.

People who have hypomagnesemia usually experience loss of weight and appetite, bloating, and muscle
pain, and they pass stools that have a high fat content.
Also, they may be listless, disoriented, confused, and
very irritable. Other symptoms of hypomagnesemia
are:


Nausea



Vomiting



Muscle weakness



Tremor



Irregular heart beat



Delusions and hallucinations



Leg and foot cramps



Muscle twitches



Changes in blood pressure.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Neonatal hypomagnesemia can occur in premature babies and in infants who have genetic parathyroid disorders or who have had blood transfusions.
This condition also occurs in babies born to magnesium-deficient mothers or to women who have:

Hypermagnesemia—An abnormally high concentration of magnesium in the blood.
Hypomagnesemia—An abnormally low concentration of magnesium in the blood.



Diabetes mellitus



Hyperparathyroidism
glands)



Toxemia (a pregnancy-related condition characterized by high blood pressure and fluid retention).

(overactive

parathyroid

Hypermagnesemia

or injections are usually prescribed to correct mild
magnesium deficiency. If the deficiency is more severe
or does not respond to treatment, magnesium sulfate
or magnesium chloride may be administered
intravenously.

Hypermagnesemia is most common in patients
whose kidneys cannot excrete the magnesium they
derive from food or take as medication. This condition
can also develop in patients who take magnesium
salts, or in healthy people who use large quantities of
magnesium-containing antacids, laxatives, or analgesics (pain relievers).

Doctors usually prescribe diuretics (urine-producing drugs) for patients with hypermagnesemia and
advise them to drink more fluids to flush the excess
mineral from the body. Patients whose magnesium
levels are extremely high may need mechanical support to breathe and to circulate blood throughout
their bodies.

Magnesium poisoning can cause severe diarrhea in
young people, and mask the symptoms of other illnesses. Very high overdoses can lead to coma. The risk
of complications of magnesium poisoning is greatest
for:

Intravenously administered calcium gluconate
may reverse damage caused by excess magnesium.
Intravenous furosemide (Lasix) or ethacrynic acid
(Edecrin) can increase magnesium excretion in
patients who get enough fluids and whose kidneys
are functioning properly.



Elderly people with inefficient kidney function



Patients with kidney problems or intestinal disorders



People who use antihistamines, muscle relaxants, or
narcotics.

Severe dehydration or an overdose of supplements taken to counteract hypomagnesemia can also
cause this condition.
People who have hypermagnesemia may feel
flushed and drowsy, perspire heavily, and have diarrhea. Breathing becomes shallow, reflexes diminish,
and the patient becomes unresponsive. Muscle weakness and hallucinations are common. The patient’s
heart beat slows dramatically and blood pressure
plummets. Extreme toxicity, which can lead to coma
and cardiac arrest, can be fatal.

In an emergency, dialysis can provide temporary
relief for patients whose kidney function is poor or
who are unable to excrete excess minerals.

Prognosis
Because imbalances may recur if the underlying
condition is not eliminated, monitoring of magnesium
levels should continue after treatment has been
completed.

Prevention
Most people consume adequate amounts of
magnesium in the food they eat. Dietary supplements
can be used safely, but should only be used under a
doctor’s supervision.

Diagnosis
Blood tests are used to measure magnesium levels.

Resources
OTHER

Treatment
The goal of treatment is to identify and correct the
cause of the imbalance. Oral magnesium supplements
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Mineral Guide.’’ CNN Page. May 2, 1998. <http://
www.cnn.com/HEALTH>.

Maureen Haggerty
2307

Magnesium imbalance

Severe magnesium deficiency can cause seizures,
especially in children.

Magnetic field therapy

Magnetic field therapy
Definition
Magnetic therapy is the use of magnets to relieve
pain in various areas of the body.

Purpose
Some of the benefits that magnetic therapy claims
to provide include:


pain relief



reduction of swelling



improved tissue alkalinization



more restful sleep



increased tissue oxygenation



relief of stress



increased levels of cellular oxygen



improved blood circulation



anti-infective activity

Description
Origins
Magnetic therapy dates as far back as the ancient
Egyptians. Magnets have long been believed to have
healing powers associated with muscle pain and stiffness. Chinese healers as early as 200 B.C. were said to
use magnetic lodestones on the body to correct
unhealthy imbalances in the flow of qi, or energy.
The ancient Chinese medical text known as The
Yellow Emperor’s Canon of Internal Medicine
describes this procedure. The Vedas, or ancient
Hindu scriptures, also mention the treatment of diseases with lodestones. The word ‘‘lodestone’’ or leading stone, came from the use of these stones as
compasses. The word ‘‘magnet’’ probably stems from
the Greek Magnes lithos, or ‘‘stone from Magnesia,’’ a
region of Greece rich in magnetic stones. The Greek
phrase later became magneta in Latin.
Sir William Gilbert’s 1600 treatise, De Magnete,
was the first scholarly attempt to explain the nature of
magnetism and how it differed from the attractive
force of static electricity. Gilbert allegedly used magnets to relieve the arthritic pains of Queen Elizabeth I.
Contemporary American interest in magnetic therapy
began in the 1990s, as several professional golfers and
football players offered testimony that the devices
seemed to cure their nagging aches and injuries.
2308

Many centuries ago, the earth was surrounded by
a much stronger magnetic field than it is today. Over
the past 155 years, scientists have been studying the
decline of this magnetic field and the effects it has had
on human health. When the first cosmonauts and
astronauts were going into space, physicians noted
that they experienced bone calcium loss and muscle
cramps when they were out of the Earth’s magnetic
field for any extended period of time. After this discovery was made, artificial magnetic fields were placed
in the space capsules.
There are two theories that are used to explain
magnetic therapy. One theory maintains that magnets
produce a slight electrical current. When magnets are
applied to a painful area of the body, the nerves in that
area are stimulated, thus releasing the body’s natural
painkillers. The other theory maintains that when magnets are applied to a painful area of the body, all the
cells in that area react to increase blood circulation, ion
exchange, and oxygen flow to the area. Magnetic fields
attract and repel charged particles in the bloodstream,
increasing blood flow and producing heat. Increased
oxygen in the tissues and blood stream is thought to
make a considerable difference in the speed of healing.

Preparations
There are no special preparations for using magnetic therapy other than purchasing a product that is
specific for the painful area being treated. Products
available in a range of prices include necklaces and
bracelets; knee, back, shoulder and wrist braces; mattress pads; gloves; shoe inserts; and more.

Precautions
The primary precaution involved with magnetic
therapy is to recognize the expense of this therapy.
Magnets have become big business; they can be
found in mail-order catalogs and stores ranging from
upscale department stores to specialty stores. As is the
case with many popular self-administered therapies,
many far-fetched claims are being made about the
effectiveness of magnetic therapy. Consumers should
adopt a ‘‘let the buyer beware’’ approach to magnetic
therapy. Persons who are interested in this form of
treatment should try out a small, inexpensive item to
see if it works for them before investing in the more
expensive products.

Side effects
There are very few side effects from using magnetic therapy. Generally, patients using this therapy
GALE ENCYCLOPEDIA OF MEDICINE

Research and general acceptance
Magnetic therapy is becoming more and more
widely accepted as an alternative method of pain relief.
Since the late 1950s, hundreds of studies have demonstrated the effectiveness of magnetic therapy. In 1997,
a group of physicians at Baylor College of Medicine in
Houston, Texas studied the use of magnetic therapy in
50 patients who had developed polio earlier in life.
These patients had muscle and joint pain that standard
treatments failed to manage. In this study, 29 of the
patients wore a magnet taped over a trouble spot, and
21 others wore a nonmagnetic device. Neither the
researchers nor the patients were told which treatment
they were receiving (magnetic or nonmagnetic). As is
the case with most studies involving a placebo, some of
the patients responded to the nonmagnetic therapy,
but 75% of those using the magnetic therapy reported
feeling much better.
In another study at New York Medical College in
Valhalla, New York, a neurologist tested magnetic
therapy on a group of 19 men and women complaining
of moderate to severe burning, tingling, or numbness in
their feet. Their problems were caused by diabetes
or other conditions present such as alcoholism. This
group of patients wore a magnetic insole inside one of
their socks or shoes for 24 hours a day over a twomonth period, except while bathing. They wore a nonmagnetic insert in their other sock or shoe. Then for
two months they wore magnetic inserts on both feet.
By the end of the study, nine out of ten of the diabetic
patients reported relief, while only three of nine nondiabetic patients reported relief. The neurologist in
charge of the study believes that this study opens the
door to additional research into magnetic therapy for
diabetic patients. He plans a larger follow-up study in
the near future.
As of 2000, a federally funded study is underway
at the University of Virginia. This study is evaluating
the effectiveness of magnetic mattress pads in easing
the muscle pain, stiffness and fatigue associated with
fibromyalgia.
Magnetic therapy is also being studied in the
treatment of depression in patients with bipolar
disorder. A procedure called repeated transcranial
magnetic stimulation has shown promise in treating
this condition. In this particular study, patients with
depression had a lower relapse rate than did those
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Fibromyalgia—A chronic syndrome characterized
by fatigue, widespread muscular pain, and pain at
specific points on the body.
Lodestone—A variety of magnetite that possesses
magnetic polarity.
Transcranial magnetic stimulation—A procedure
used to treat patients with depression.

using electroconvulsive therapy. Unlike electroconvulsive therapy, patients using magnetic therapy did
not suffer from seizures, memory lapses, or impaired
thinking.
Resources
PERIODICALS

‘‘Magnets for Pain Relief: Attractive but Unproven.’’ Tufts
University Health and Nutrition Letter 1999: 3.
Vallbona, C. ‘‘Evolution of Magnetic Therapy from
Alternative to Traditional Medicine.’’ Physical
Medicine Rehabilitation Clinics of North America 1999:
729-54.

Kim A. Sharp, M.Ln.

Magnetic resonance imaging
Definition
Magnetic resonance imaging (MRI) is the newest,
and perhaps most versatile, medical imaging technology available. Doctors can get highly refined images of
the body’s interior without surgery, using MRI. By
using strong magnets and pulses of radio waves to
manipulate the natural magnetic properties in the
body, this technique makes better images of organs
and soft tissues than those of other scanning technologies. MRI is particularly useful for imaging the brain
and spine, as well as the soft tissues of joints and the
interior structure of bones. The entire body is visible to
the technique, which poses few known health risks.

Purpose
MRI was developed in the 1980s. The latest additions to MRI technology are angiography (MRA)
and spectroscopy (MRS). MRA was developed to
2309

Magnetic resonance imaging

find that it either works for them or it does not.
Patients using transcranial magnetic stimulation for
the treatment of depression reported mild headache as
their only side effect.

Magnetic resonance imaging

study blood flow, while MRS can identify the chemical composition of diseased tissue and produce color
images of brain function. The many advantages of
MRI include:


Detail. MRI creates precise images of the body based
on the varying proportions of magnetic elements in
different tissues. Very minor fluctuations in chemical
composition can be determined. MRI images have
greater natural contrast than standard x rays, computed tomography scan (CT scan), or ultrasound, all
of which depend on the differing physical properties
of tissues. This sensitivity lets MRI distinguish fine
variations in tissues deep within the body. It also is
particularly useful for spotting and distinguishing
diseased tissues (tumors and other lesions) early in
their development. Often, doctors prescribe an MRI
scan to more fully investigate earlier findings of the
other imaging techniques.



Scope. The entire body can be scanned, from head to
toe and from the skin to the deepest recesses of the
brain. Moreover, MRI scans are not obstructed by
bone, gas, or body waste, which can hinder other
imaging techniques. (Although the scans can be
degraded by motion such as breathing, heartbeat,
and normal bowel activity.) The MRI process produces cross-sectional images of the body that are as
sharp in the middle as on the edges, even of the brain
through the skull. A close series of these two-dimensional images can provide a three-dimensional view
of a targeted area.



Safety. MRI does not depend on potentially harmful
ionizing radiation, as do standard x-ray and CT
scans. There are no known risks specific to the procedure, other than for people who might have metal
objects in their bodies.

MRI is being used increasingly during operations,
particularly those involving very small structures in
the head and neck, as well as for preoperative assessment and planning. Intraoperative MRIs have shown
themselves to be safe as well as feasible, and to
improve the surgeon’s ability to remove the entire
tumor or other abnormality.
Given all the advantages, doctors would undoubtedly prescribe MRI as frequently as ultrasound scanning, but the MRI process is complex and costly. The
process requires large, expensive, and complicated
equipment; a highly trained operator; and a doctor
specializing in radiology. Generally, MRI is prescribed only when serious symptoms and/or negative
results from other tests indicate a need. Many times
another test is appropriate for the type of diagnosis
needed.
2310

Doctors may prescribe an MRI scan of different
areas of the body.


Brain and head. MRI technology was developed
because of the need for brain imaging. It is one of
the few imaging tools that can see through bone (the
skull) and deliver high quality pictures of the brain’s
delicate soft tissue structures. MRI may be needed
for patients with symptoms of a brain tumor, stroke,
or infection (like meningitis). MRI also may be
needed when cognitive and/or psychological symptoms suggest brain disease (like Alzheimer’s or
Huntington’s diseases, or multiple sclerosis), or
when developmental retardation suggests a birth
defect. MRI can also provide pictures of the sinuses
and other areas of the head beneath the face. Recent
refinements in MRI technology may make this form
of diagnostic imaging even more useful in evaluating
patients with brain cancer, stroke, schizophrenia, or
epilepsy. In particular, a new 3-D approach to MRI
imaging known as diffusion tensor imaging, or DTI,
measures the flow of water within brain tissue, allowing the radiologist to tell where the normal flow of
fluid is disrupted, and to distinguish more clearly
between cancerous and normal brain tissue. The
introduction of DTI has led to a technique known
as fiber tracking, which allows the neurosurgeon to
tell whether a space-occupying brain tumor has
damaged or displaced the nerve pathways in the
white matter of the brain. This information in turn
improves the surgeon’s accuracy during the actual
operation.



Spine. Spinal problems can create a host of seemingly
unrelated symptoms. MRI is particularly useful for
identifying and evaluating degenerated or herniated
spinal discs. It can also be used to determine the
condition of nerve tissue within the spinal cord.



Joint. MRI scanning is most commonly used to diagnose and assess joint problems. MRI can provide
clear images of the bone, cartilage, ligament, and
tendon that comprise a joint. MRI can be used to
diagnose joint injuries due to sports, advancing age,
or arthritis. MRI can also be used to diagnose
shoulder problems, like a torn rotator cuff. MRI
can also detect the presence of an otherwise hidden
tumor or infection in a joint, and can be used to
diagnose the nature of developmental joint abnormalities in children.



Skeleton. The properties of MRI that allow it to see
through the skull also allow it to view the inside of
bones. It can be used to detect bone cancer, inspect the
marrow for leukemia and other diseases, assess bone
loss (osteoporosis), and examine complex fractures.
GALE ENCYCLOPEDIA OF MEDICINE

The rest of the body. While CT and ultrasound
satisfy most chest, abdominal, and general body
imaging needs, MRI may be needed in certain circumstances to provide better pictures or when
repeated scanning is required. The progress of some
therapies, like liver cancer therapy, needs to be monitored, and the effect of repeated x-ray exposure is a
concern.

Precautions
MRI scanning should not be used when there is
the potential for an interaction between the strong
MRI magnet and metal objects that might be
imbedded in a patient’s body. The force of magnetic
attraction on certain types of metal objects (including
surgical steel) could move them within the body and
cause serious injury. Metal may be imbedded in a
person’s body for several reasons.


Medical. People with implanted cardiac pacemakers,
metal aneurysm clips, or who have had broken bones
repaired with metal pins, screws, rods, or plates must
tell their radiologist prior to having an MRI scan. In
some cases (like a metal rod in a reconstructed leg)
the difficulty may be overcome.



Injury. Patients must tell their doctors if they have
bullet fragments or other metal pieces in their body
from old wounds. The suspected presence of metal,
whether from an old or recent wound, should be
confirmed before scanning.



Occupational. People with significant work exposure
to metal particles (working with a metal grinder, for
example) should discuss this with their doctor and
radiologist. The patient may need prescan testing–
usually a single, regular x ray of the eyes to see if any
metal is present.

Chemical agents designed to improve the picture
and/or allow for the imaging of blood or other fluid
flow during MRA may be injected. In rare cases,
patients may be allergic to or intolerant of these
agents, and these patients should not receive them. If
these chemical agents are to be used, patients should
discuss any concerns they have with their doctor and
radiologist.
The potential side effects of magnetic and electric
fields on human health remain a source of debate. In
particular, the possible effects on an unborn baby are
not well known. Any woman who is, or may be, pregnant should carefully discuss this issue with her doctor
and radiologist before undergoing a scan.
As with all medical imaging techniques, obesity
greatly interferes with the quality of MRI.
GALE ENCYCLOPEDIA OF MEDICINE

Description
In essence, MRI produces a map of hydrogen
distribution in the body. Hydrogen is the simplest
element known, the most abundant in biological tissue, and one that can be magnetized. It will align itself
within a strong magnetic field, like the needle of a
compass. The earth’s magnetic field is not strong
enough to keep a person’s hydrogen atoms pointing
in the same direction, but the superconducting magnet
of an MRI machine can. This comprises the ‘‘magnetic’’ part of MRI.
Once a patient’s hydrogen atoms have been
aligned in the magnet, pulses of very specific radio
wave frequencies are used to knock them back out of
alignment. The hydrogen atoms alternately absorb
and emit radio wave energy, vibrating back and forth
between their resting (magnetized) state and their agitated (radio pulse) state. This comprises the ‘‘resonance’’ part of MRI.
The MRI equipment records the duration,
strength, and source location of the signals emitted
by the atoms as they relax and translates the data
into an image on a television monitor. The state of
hydrogen in diseased tissue differs from healthy tissue
of the same type, making MRI particularly good at
identifying tumors and other lesions. In some cases,
chemical agents such as gadolinium can be injected to
improve the contrast between healthy and diseased
tissue.
A single MRI exposure produces a two-dimensional
image of a slice through the entire target area. A series
of these image slices closely spaced (usually less than
half an inch) makes a virtual three-dimensional view of
the area.
Magnetic resonance spectroscopy (MRS) is different from MRI because MRS uses a continuous band
of radio wave frequencies to excite hydrogen atoms in
a variety of chemical compounds other than water.
These compounds absorb and emit radio energy at
characteristic frequencies, or spectra, which can be
used to identify them. Generally, a color image is
created by assigning a color to each distinctive spectral
emission. This comprises the ‘‘spectroscopy’’ part of
MRS. MRS is still experimental and is available in
only a few research centers.
Doctors primarily use MRS to study the brain and
disorders, like epilepsy, Alzheimer’s disease, brain
tumors, and the effects of drugs on brain growth and
metabolism. The technique is also useful in evaluating
metabolic disorders of the muscles and nervous
system.
2311

Magnetic resonance imaging



Magnetic resonance imaging

Depending on the area to be imaged, the radiowave transmitters will be positioned in different
locations.


For the head and neck, a helmet-like hat is worn.



For the spine, chest, and abdomen, the patient will be
lying on the transmitters.



For the knee, shoulder, or other joint, the transmitters will be applied directly to the joint.

Additional probes will monitor vital signs (like
pulse, respiration, etc.).

MRI body scans of a man, woman, and child. (Simon Fraser,
Photo Researchers. Reproduced by permission.)

Magnetic resonance angiography (MRA) is
another variation on standard MRI. MRA, like
other types of angiography, looks specifically at fluid
flow within the blood (vascular) system, but does so
without the injection of dyes or radioactive tracers.
Standard MRI cannot make a good picture of flowing
blood, but MRA uses specific radio pulse sequences to
capture usable signals. The technique is generally used
in combination with MRI to obtain images that show
both vascular structure and flow within the brain and
head in cases of stroke, or when a blood clot or aneurysm is suspected.
Regardless of the exact type of MRI planned, or
area of the body targeted, the procedure involved is
basically the same and occurs in a special MRI suite.
The patient lies back on a narrow table and is made as
comfortable as possible. Transmitters are positioned
on the body and the cushioned table that the patient is
lying on moves into a long tube that houses the magnet. The tube is as long as an average adult lying down,
and the tube is narrow and open at both ends. Once
the area to be examined has been properly positioned,
a radio pulse is applied. Then a two-dimensional
image corresponding to one slice through the area is
made. The table then moves a fraction of an inch and
the next image is made. Each image exposure takes
several seconds and the entire exam will last anywhere
from 30-90 minutes. During this time, the patient is
not allowed to move. If the patient moves during the
scan, the picture will not be clear.
2312

The process is very noisy and confining. The
patient hears a thumping sound for the duration of
the procedure. Since the procedure is noisy, music
supplied via earphones is often provided. Some
patients get anxious or panic because they are in the
small, enclosed tube. This is why vital signs are monitored and the patient and medical team can communicate between each other. If the chest or abdomen are
to be imaged, the patient will be asked to hold his/her
breath as each exposure is made. Other instructions
may be given to the patient, as needed. In many cases,
the entire examination will be performed by an MRI
operator who is not a doctor. However, the supervising radiologist should be available to consult as necessary during the exam, and will view and interpret the
results sometime later.

Preparation
In some cases (such as for MRI brain scanning or
an MRA), a chemical designed to increase image contrast may be given by the radiologist immediately before
the exam. If a patient suffers from anxiety or claustrophobia, drugs may be given to help the patient relax.
The patient must remove all metal objects
(watches, jewelry, eye glasses, hair clips, etc). Any
magnetized objects (like credit and bank machine
cards, audio tapes, etc.) should be kept far away
from the MRI equipment because they can be erased.
The patient cannnot bring their wallet or keys into the
MRI machine. The patient may be asked to wear
clothing without metal snaps, buckles, or zippers,
unless a medical gown is worn during the procedure.
The patient may be asked to remove any hair spray,
hair gel, or cosmetics that may interfere with the scan.

Aftercare
No aftercare is necessary, unless the patient
received medication or had a reaction to a contrast
agent. Normally, patients can immediately return to
their daily activities. If the exam reveals a serious
GALE ENCYCLOPEDIA OF MEDICINE

Angiography—Any of the different methods for
investigating the condition of blood vessels, usually
via a combination of radiological imaging and
injections of chemical tracing and contrasting
agents.
Diffusion tensor imaging (DTI)—A refinement of
magnetic resonance imaging that allows the doctor
to measure the flow of water and track the pathways of white matter in the brain. DTI is able to
detect abnormalities in the brain that do not show
up on standard MRI scans.
Gadolinium—A very rare metallic element useful
for its sensitivity to electromagnetic resonance,
among other things. Traces of it can be injected
into the body to enhance the MRI pictures.
Hydrogen—The simplest, most common element
known in the universe. It is composed of a single
electron (negatively charged particle) circling a
nucleus consisting of a single proton (positively
charged particle). It is the nuclear proton of hydrogen that makes MRI possible by reacting resonantly
to radio waves while aligned in a magnetic field.
Ionizing radiation—Electromagnetic radiation that
can damage living tissue by disrupting and destroying individual cells. All types of nuclear decay
radiation (including x rays) are potentially ionizing.
Radio waves do not damage organic tissues they
pass through.
Magnetic field—The three-dimensional area surrounding a magnet, in which its force is active.
During MRI, the patient’s body is permeated by
the force field of a superconducting magnet.
Radio waves— Electromagnetic energy of the frequency range corresponding to that used in radio
communications, usually 10,000 cycles per second
to 300 billion cycles per second. Radio waves are
the same as visible light, x rays, and all other types
of electromagnetic radiation, but are of a higher
frequency.

condition that requires more testing and/or treatment,
appropriate information and counseling will be
needed.

Risks
MRI poses no known health risks to the patient
and produces no physical side effects. Again, the
GALE ENCYCLOPEDIA OF MEDICINE

potential effects of MRI on an unborn baby are not
well known. Any woman who is, or may be, pregnant,
should carefully discuss this issue with her doctor and
radiologist before undergoing a scan.

Normal results
A normal MRI, MRA, or MRS result is one that
shows the patient’s physical condition to fall within
normal ranges for the target area scanned.

Abnormal results
Generally, MRI is prescribed only when serious
symptoms and/or negative results from other tests
indicate a need. There often exists strong evidence of
a condition that the scan is designed to detect and
assess. Thus, the results will often be abnormal, confirming the earlier diagnosis. At that point, further
testing and appropriate medical treatment is needed.
For example, if the MRI indicates the presence of a
brain tumor, an MRS may be prescribed to determine
the type of tumor so that aggressive treatment can
begin immediately without the need for a surgical
biopsy.
Resources
PERIODICALS

Clark, C. A., T. R. Barrick, M. M. Murphy, and B. A. Bell.
‘‘White Matter Fiber Tracking in Patients with SpaceOccupying Lesions of the Brain: A New Technique for
Neurosurgical Planning?’’ Neuroimage 20 (November
2003): 1601–1608.
Hendler, T., P. Pianka, M. Sigal, et al. ‘‘Delineating Gray
and White Matter Involvement in Brain Lesions: Threedimensional Alignment of Functional Magnetic
Resonance and Diffusion-Tensor Imaging.’’ Journal of
Neurosurgery 99 (December 2003): 1018–1027.
Kubicki, M., C. F. Westin, P. G. Nestor, et al. ‘‘Cingulate
Fasciculus Integrity Disruption in Schizophrenia: A
Magnetic Resonance Diffusion Tensor Imaging
Study.’’ Biological Psychiatry 54 (December 1, 2003):
1171–1180.
Mahmoud-Ghoneim, D., G. Toussaint, J. M. Constans, and
J. D. de Certaines. ‘‘Three-Dimensional Texture
Analysis in MRI: A Preliminary Evaluation in
Gliomas.’’ Magnetic Resonance Imaging 21 (November
2003): 983–987.
Rees, J. ‘‘Advances in Magnetic Resonance Imaging of
Brain Tumours.’’ Current Opinion in Neurology 16
(December 2003): 643–650.
Satoh, T., K. Onoda, and S. Tsuchimoto. ‘‘Intraoperative
Evaluation of Aneurysmal Architecture: Comparative
Study with Transluminal Images of 3D MR and CT
Angiograms.’’ American Journal of Neuroradiology 24
(November-December 2003): 1975–1981.
2313

Magnetic resonance imaging

KEY TERMS

Malabsorption syndrome

ORGANIZATIONS

Risk factors for malabsorption syndrome include:

American College of Radiology. 1891 Preston White Drive,
Reston, VA 22091. (800) 227-5463. <http://
www.acr.org>.
American Society of Radiologic Technologists. 15000
Central Ave. SE, Albuquerque, NM 87123-3917. (505)
298-4500. <http://www.asrt.org>.
Center for Devices and Radiological Health. United States
Food and Drug Administration. 1901 Chapman Ave.,
Rockville, MD 20857. (301) 443-4109. <http://
www.fda.gov/cdrh>.

Kurt Richard Sternlof
Rebecca J. Frey, PhD

Magnetic resonance spectroscopy see
Magnetic resonance imaging



premature birth



family history of malabsorption or cystic fibrosis



use of certain drugs, such as mineral oil or other
laxatives



travel to foreign countries



intestinal surgery, including bowel transplantation



excess alcohol consumption.

The most common symptoms of malabsorption
include:


Anemia, with weakness and fatigue due to inadequate absorption of vitamin B12, iron, and folic acid



Diarrhea, steatorrhea (excessive amount of fat in the
stool), and abdominal distention with cramps, bloating, and gas due to impaired water and carbohydrate
absorption, and irritation from unabsorbed fatty
acids. The individual may also report explosive diarrhea with greasy, foul-smelling stools.



Edema (fluid retention in the body’s tissues) due to
decreased protein absorption



Malnutrition and weight loss due to decreased fat,
carbohydrate, and protein absorption. Weight may
be 80–90% of usual weight despite increased oral
intake of nutrients.



Muscle cramping due to decreased vitamin D, calcium, and potassium levels



Muscle wasting and atrophy due to decreased protein absorption and metabolism



Perianal skin burning, itching, or soreness due to
frequent loose stools.

Major depression see Depressive disorders
Major tranquilizers see Antipsychotic drugs

Malabsorption syndrome
Definition
Malabsorption syndrome is an alteration in the
ability of the intestine to absorb nutrients adequately
into the bloodstream. It may refer to malabsorption of
one specific nutrient or for specific carbohydrates,
fats, or trace elements (micronutrients).

Causes and symptoms
Protein, fats, and carbohydrates (macronutrients)
normally are absorbed in the small intestine; the small
bowel also absorbs about 80% of the eight to ten liters
of fluid ingested daily. There are many different conditions that affect fluid and nutrient absorption by the
intestine. A fault in the digestive process may result
from failure of the body to produce the enzymes
needed to digest certain foods. Congenital structural
defects or diseases of the pancreas, gall bladder, or
liver may alter the digestive process. Inflammation,
infection, injury, or surgical removal of portions of
the intestine may also result in absorption problems;
reduced length or surface area of intestine available
for fluid and nutrient absorption can result in malabsorption. Radiation therapy may injure the mucosal
lining of the intestine, resulting in diarrhea that may
not become evident until several years later. The use of
some antibiotics can also affect the bacteria that normally live in the intestine and affect intestinal function.
2314

Irregular heart rhythms may also result from
inadequate levels of potassium and other electrolytes.
Blood clotting disorders may occur due to a vitamin K
deficiency. Children with malabsorption syndrome
often exhibit a failure to grow and thrive.
Several disorders can lead to malabsorption syndrome, including cystic fibrosis, chronic pancreatitis,
lactose intolerance, and gluten enteropathy (nontropical sprue.)
Tropical sprue is a malabsorptive disorder that is
uncommon in the United States, but seen more often
in people from the Caribbean, India, or southeast
Asia. Although its cause is unknown, it is thought to
be related to environmental factors, including infection, intestinal parasites, or possibly the consumption
of certain food toxins. Symptoms often include a sore
tongue, anemia, weight loss, along with diarrhea and
passage of fatty stools.
GALE ENCYCLOPEDIA OF MEDICINE

Short bowel syndromes—which may be present at
birth (congenital) or the result of surgery—reduce the
surface area of the bowel available to absorb nutrients
and can also result in malabsorption syndrome.
Congenital short bowel syndrome occurs in about 24
out of 100,000 live births and has a high mortality rate
(about 38%).

After four hours the patient can eat food without
interfering with the test. As of the early 2000s, the
M2A system is used to evaluate gastrointestinal bleeding from unknown causes, inflammatory bowel
disease, some malabsorption syndromes, and to
monitor surgical patients following small-bowel
transplantation.
Laboratory studies of the blood may include:


Serum cholesterol. May be low due to decreased fat
absorption and digestion.



Serum sodium, potassium, and chloride. May be low
due to electrolyte losses with diarrhea.



Serum calcium. May be low due to vitamin D and
amino acid malabsorption.



Serum protein and albumin. May be low due to
protein losses.



Serum vitamin A and carotene. May be low due to
bile salt deficiency and impaired fat absorption.



D-xylose test. Decreased excretion may indicate
malabsorption.



Schilling test. May indicate malabsorption of
vitamin B12.

Diagnosis
The diagnosis of malabsorption syndrome and
identification of the underlying cause can require
extensive diagnostic testing. The first phase involves
a thorough medical history and physical examination
by a physician, who will then determine the appropriate laboratory studies and x rays to assist in diagnosis.
A 72-hour stool collection may be ordered for fecal fat
measurement; increased fecal fat in the stool collected
indicates malabsorption. A biopsy of the small intestine may be done to assist in differentiating between
malabsorption syndrome and small bowel disease.
Ultrasound, computed tomography scan (CT scan),
magnetic resonance imaging (MRI), barium enema, or
other x rays to identify abnormalities of the gastrointestinal tract and pancreas may also be ordered.
A newer method of obtaining diagnostic information about the small intestine was approved by the
Food and Drug Administration (FDA) in 2001.
Known as the M2A Imaging System, the device was
developed by a company in Atlanta, Georgia. The
M2A system consists of an imaging capsule, a portable
belt-pack image receiver and recorder, and a specially
modified computer. The patient swallows the capsule,
which is the size of a large pill. A miniature lens in the
capsule transmits images through an antenna/transmitter to the belt-pack receiver, which the patient
wears under ordinary clothing as he or she goes
about daily activities. The belt-pack recording device
is returned after seven or eight hours to the doctor,
who then examines the images recorded as a digital
video. The capsule itself is simply allowed to pass
through the digestive tract.
Preparation requires only fasting the night before
the M2A examination and taking nothing but clear
liquids for two hours after swallowing the capsule.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Fluid and nutrient monitoring and replacement is
essential for any individual with malabsorption syndrome. Hospitalization may be required when severe
fluid and electrolyte imbalances occur. Consultation
with a dietitian to assist with nutritional support and
meal planning is helpful. If the patient is able to eat,
the diet and supplements should provide bulk and be
rich in carbohydrates, proteins, fats, minerals, and
vitamins. The patient should be encouraged to eat
several small, frequent meals throughout the day,
avoiding fluids and foods that promote diarrhea.
Intake and output should be monitored, along with
the number, color, and consistency of stools.
The individual with malabsorption syndrome
must be monitored for dehydration, including dry tongue, mouth and skin; increased thirst; low, concentrated urine output; or feeling weak or dizzy when
standing. Pulse and blood pressure should be monitored, observing for increased or irregular pulse rate,
or hypotension (low blood pressure). The individual
should also be alert for signs of nutrient, vitamin,
and mineral depletion, including nausea or vomiting;
fissures at corner of mouth; fatigue or weakness; dry,
pluckable hair; easy bruising; tingling in fingers or
toes; and numbness or burning sensation in legs or
feet. Fluid volume excess, as a result of diminished
2315

Malabsorption syndrome

Whipple’s disease is a relatively rare malabsorptive disorder, affecting mostly middle-aged men. The
cause is thought to be related to bacterial infection,
resulting in nutritional deficiencies, chronic low-grade
fever, diarrhea, joint pain, weight loss, and darkening
of the skin’s pigmentation. Other organs of the body
may be affected, including the brain, heart, lungs, and
eyes.

Malabsorption syndrome

KEY TERMS
Anemia—A decrease in the number of red blood
cells in the bloodstream, characterized by pallor,
loss of energy, and generalized weakness.
Atrophy—A wasting away of a tissue or organ,
often because of insufficient nutrition.
Biopsy—A tissue sample removed from the body
for examination under the microscope.
Cystic fibrosis—A hereditary genetic disorder that
occurs most often in Caucasians. Thick, sticky
secretions from mucus-producing glands cause
blockages in the pancreatic ducts and the airways.
Edema—From the Greek word meaning swelling,
an excessive accumulation of fluid in the tissue
spaces. Excessive generalized edema may also be
referred to as ascites.
Gluten enteropathy—A hereditary malabsorption
disorder caused by sensitivity to gluten, a protein
found in wheat, rye, barley, and oats. Also called
non-tropical sprue or celiac disease.
Intestines—The intestines, also known as the
bowels, are divided into the large and small intestines. They extend from the stomach to the anus.
Short bowel syndrome—A condition in which the
bowel is not as long as normal, either because of
surgery or because of a congenital defect. Because
the bowel has less surface area to absorb nutrients,
it can result in malabsorption syndrome.
Steatorrhea—An excessive amount of fat in the
stool.
Trace elements—A group of elements that are present in the human body in very small amounts but
are nonetheless important to good health. They
include chromium, copper, cobalt, iodine, iron,
selenium, and zinc. Trace elements are also called
micronutrients.

protein stores, may require fluid intake restrictions.
The physician should also be notified of any shortness
of breath.
Other specific medical management for malabsorption syndrome is dependent upon the cause. Treatment
for tropical sprue consists of folic acid supplements
and long-term antibiotics. Depending on the severity
of the disorder, this treatment may be continued for six
months or longer. Whipple’s disease also may require
long-term use of antibiotics, such as tetracycline.
2316

Management of some individuals with malabsorption
syndrome may require injections of vitamin B12 and
oral iron supplements. The doctor may also prescribe
enzymes to replace missing intestinal enzymes, or antispasmodics to reduce abdominal cramping and associated diarrhea. People with cystic fibrosis and chronic
pancreatitis require pancreatic supplements. Those
with lactose intolerance or gluten enteropathy (nontropical sprue) will have to modify their diets to avoid
foods that they cannot properly digest.

Prognosis
The expected course for the individual with
malabsorption syndrome varies depending on the
cause. The onset of symptoms may be slow and difficult to diagnose. Treatment may be long, complicated,
and changed often for optimal effectiveness. Patience
and a positive attitude are important in controlling or
curing the disorder. Careful monitoring is necessary to
prevent additional illnesses cause by nutritional
deficiencies.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Malabsorption Syndromes.’’ Section 3, Chapter 30. In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Adler, Douglas J., MD, and Christopher J. Gostout, MD.
‘‘Wireless Capsule Endoscopy.’’ Hospital Physician
May 2003: 17–22.
Forsberg, G., A. Fahlgren, P. Horstedt, et al. ‘‘Presence of
Bacteria and Innate Immunity of Intestinal Epithelium
in Childhood Celiac Disease.’’ American Journal of
Gastroenterology 99 (May 2004): 905–906.
Kumar, N., and P. A. Low. ‘‘Myeloneuropathy and Anemia
Due to Copper Malabsorption.’’ Journal of Neurology
251 (June 2004): 747–749.
Sabharwal, G., P. J. Strouse, S. Islam, and N. Zoubi.
‘‘Congenital Short-Gut Syndrome.’’ Pediatric
Radiology 34 (May 2004): 424–427.
Thompson, B. F., L. C. Fry, C. D. Wells, et al. ‘‘The Spectrum
of GI Strongyloidiasis: An Endoscopic-Pathologic
Study.’’ Gastrointestinal Endoscopy 59 (June 2004):
906–910.
Wales, P. W., N. de Silva, J. Kim, et al. ‘‘Neonatal Short
Bowel Syndrome: Population-Based Estimates of
Incidence and Mortality Rates.’’ Journal of Pediatric
Surgery 39 (May 2004): 690–695.
ORGANIZATIONS

National Digestive Diseases Information Clearinghouse.
2 Information Way, Bethesda, MD 20892-3570.
GALE ENCYCLOPEDIA OF MEDICINE

Kathleen D. Wright, RN
Rebecca J. Frey, PhD

Malaria

due to malaria infection. In some parts of Africa,
people battle up to 40 or more separate episodes of
malaria in their lifetimes. The spread of malaria is
becoming even more serious as the parasites that
cause malaria develop resistance to the drugs used to
treat the condition. In late 2002, a group of public
health researchers in Thailand reported that a combination treatment regimen involving two drugs known
as dihydroartemisinin and azithromycin shows promise in treating multidrug-resistant malaria in southeast Asia.

Definition
Malaria is a serious infectious disease spread by
certain mosquitoes. It is most common in tropical
climates. It is characterized by recurrent symptoms
of chills, fever, and an enlarged spleen. The disease
can be treated with medication, but it often recurs.
Malaria is endemic (occurs frequently in a particular
locality) in many third world countries. Isolated, small
outbreaks sometimes occur within the boundaries of
the United States.

Description
Malaria is a growing problem in the United
States. Although only about 1400 new cases were
reported in the United States and its territories in
2000, many involved returning travelers. In addition,
locally transmitted malaria has occurred in California,
Florida, Texas, Michigan, New Jersey, and New York
City. While malaria can be transmitted in blood, the
American blood supply is not screened for malaria.
Widespread malarial epidemics are far less likely to
occur in the United States, but small localized epidemics could return to the Western world. As of late
2002, primary care physicians are being advised to
screen returning travelers with fever for malaria, and
a team of public health doctors in Minnesota is recommending screening immigrants, refugees, and international adoptees for the disease—particularly those
from high-risk areas.
The picture is far more bleak, however, outside
the territorial boundaries of the United States. A
recent government panel warned that disaster looms
over Africa from the disease. Malaria infects between
300 and 500 million people every year in Africa, India,
southeast Asia, the Middle East, Oceania, and Central
and South America. A 2002 report stated that malaria
kills 2.7 million people each year, more than 75 percent
of them African children under the age of five. It is
predicted that within five years, malaria will kill about
as many people as does AIDS. As many as half a
billion people worldwide are left with chronic anemia
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Human malaria is caused by four different species
of a parasite belonging to genus Plasmodium:
Plasmodium falciparum (the most deadly), Plasmodium
vivax, Plasmodium malariae, and Plasmodium ovale.
The last two are fairly uncommon. Many animals can
get malaria, but human malaria does not spread to
animals. In turn, animal malaria does not spread to
humans.
A person gets malaria when bitten by a female
mosquito who is looking for a blood meal and is
infected with the malaria parasite. The parasites
enter the blood stream and travel to the liver, where
they multiply. When they re-emerge into the blood,
symptoms appear. By the time a patient shows symptoms, the parasites have reproduced very rapidly, clogging blood vessels and rupturing blood cells.
Malaria cannot be casually transmitted directly
from one person to another. Instead, a mosquito
bites an infected person and then passes the infection
on to the next human it bites. It is also possible to
spread malaria via contaminated needles or in blood
transfusions. This is why all blood donors are carefully
screened with questionnaires for possible exposure to
malaria.
It is possible to contract malaria in non-endemic
areas, although such cases are rare. Nevertheless, at
least 89 cases of so-called airport malaria, in which
travelers contract malaria while passing through
crowded airport terminals, have been identified since
1969.
The amount of time between the mosquito bite
and the appearance of symptoms varies, depending on
the strain of parasite involved. The incubation period
is usually between 8 and 12 days for falciparum
malaria, but it can be as long as a month for the
other types. Symptoms from some strains of P.vivax
may not appear until 8–10 months after the mosquito
bite occurred.
2317

Malaria

(800) 891-5389. Fax: (703) 738-4929. <http://
digestive.niddk.nih.gov>.

Malaria

The primary symptom of all types of malaria is the
‘‘malaria ague’’ (chills and fever). In most cases, the
fever has three stages, beginning with uncontrollable
shivering for an hour or two, followed by a rapid spike
in temperature (as high as 1068F), which lasts three to
six hours. Then, just as suddenly, the patient begins to
sweat profusely, which will quickly bring down the
fever. Other symptoms may include fatigue, severe
headache, or nausea and vomiting. As the sweating subsides, the patient typically feels exhausted and falls
asleep. In many cases, this cycle of chills, fever, and
sweating occurs every other day, or every third day, and
may last for between a week and a month. Those with
the chronic form of malaria may have a relapse as long
as 50 years after the initial infection.
Falciparum malaria is far more severe than other
types of malaria because the parasite attacks all red
blood cells, not just the young or old cells, as do other
types. It causes the red blood cells to become very
‘‘sticky.’’ A patient with this type of malaria can die
within hours of the first symptoms. The fever is prolonged. So many red blood cells are destroyed that
they block the blood vessels in vital organs (especially
the kidneys), and the spleen becomes enlarged. There
may be brain damage, leading to coma and convulsions. The kidneys and liver may fail.
Malaria in pregnancy can lead to premature delivery, miscarriage, or stillbirth.
Certain kinds of mosquitoes (called anopheles)
can pick up the parasite by biting an infected human.
(The more common kinds of mosquitoes in the United
States do not transmit the infection.) This is true for as
long as that human has parasites in his/her blood. Since
strains of malaria do not protect against each other, it is
possible to be reinfected with the parasites again and
again. It is also possible to develop a chronic infection
without developing an effective immune response.

Diagnosis
Malaria is diagnosed by examining blood under a
microscope. The parasite can be seen in the blood
smears on a slide. These blood smears may need to
be repeated over a 72-hour period in order to make a
diagnosis. Antibody tests are not usually helpful
because many people developed antibodies from past
infections, and the tests may not be readily available.
A new laser test to detect the presence of malaria
parasites in the blood was developed in 2002, but is
still under clinical study.
Two new techniques to speed the laboratory diagnosis of malaria show promise as of late 2002. The first
2318

is acridine orange (AO), a staining agent that works
much faster (3–10 min) than the traditional Giemsa
stain (45–60 min) in making the malaria parasites
visible under a microscope. The second is a bioassay
technique that measures the amount of a substance
called histadine-rich protein II (HRP2) in the patient’s
blood. It allows for a very accurate estimation of
parasite development. A dip strip that tests for the
presence of HRP2 in blood samples appears to be
more accurate in diagnosing malaria than standard
microscopic analysis.
Anyone who becomes ill with chills and fever after
being in an area where malaria exists must see a doctor
and mention their recent travel to endemic areas. A
person with the above symptoms who has been in a
high-risk area should insist on a blood test for malaria.
The doctor may believe the symptoms are just the
common flu virus. Malaria is often misdiagnosed by
North American doctors who are not used to seeing
the disease. Delaying treatment of falciparum malaria
can be fatal.

Treatment
Falciparum malaria is a medical emergency that
must be treated in the hospital. The type of drugs, the
method of giving them, and the length of the treatment
depend on where the malaria was contracted and how
sick the patient is.
For all strains except falciparum, the treatment
for malaria is usually chloroquine (Aralen) by mouth
for three days. Those falciparum strains suspected to
be resistant to chloroquine are usually treated with a
combination of quinine and tetracycline. In countries
where quinine resistance is developing, other treatments may include clindamycin (Cleocin), mefloquin
(Lariam), or sulfadoxone/pyrimethamine (Fansidar).
Most patients receive an antibiotic for seven days.
Those who are very ill may need intensive care
and intravenous (IV) malaria treatment for the first
three days.
Anyone who acquired falciparum malaria in the
Dominican Republic, Haiti, Central America west of
the Panama Canal, the Middle East, or Egypt can still
be cured with chloroquine. Almost all strains of falciparum malaria in Africa, South Africa, India, and
southeast Asia are now resistant to chloroquine. In
Thailand and Cambodia, there are strains of falciparum malaria that have some resistance to almost
all known drugs.
A patient with falciparum malaria needs to be
hospitalized and given antimalarial drugs in different
GALE ENCYCLOPEDIA OF MEDICINE

Fertilization

Gametocytes
become differentiated
into egg and sperm

MOSQUITO

Salivary gland

Sporozoites
released and
migrate to
salivary gland

Oocyst
Sporogony
occurs
Sporozoites
develop

Sporozoite

HUMAN

Blood vessel
of human host
Sporozoite
entering liver cell

Liver

Trophozoite

Gametocytes

Sporozoite becomes
merozoite

CYCLE IN
LIVER CELLS

Infect other
liver cells
or enter red
blood cells

Ameboid
form
CYCLE IN
BLOOD CELLS

Liberation of
merozoites

Merozoite entering
red cell
INCUBATION PERIOD

CHILLS AND FEVER STAGE

The life cycle of Plasmodium vivax, the parasite that causes malaria. (Illustration by Hans & Cassady.)

GALE ENCYCLOPEDIA OF MEDICINE

2319

Malaria

Zygote

Stomach

Malaria

combinations and doses depending on the resistance
of the strain. The patient may need IV fluids, red blood
cell transfusions, kidney dialysis, and assistance
breathing.
A drug called primaquine may prevent relapses
after recovery from P. vivax or P. ovale. These relapses
are caused by a form of the parasite that remains in the
liver and can reactivate months or years later.
Another new drug, halofantrine, is available
abroad. While it is licensed in the United States, it is
not marketed in this country and it is not recommended by the Centers for Disease Control and
Prevention in Atlanta.

Alternative treatments
The Chinese herb qiinghaosu (the Western name
is artemisinin) has been used in China and southeast
Asia to fight severe malaria, and became available in
Europe in 1994. Because this treatment often fails, it is
usually combined with another antimalarial drug
(mefloquine) to boost its effectiveness. It is not available in the United States and other parts of the developed world due to fears of its toxicity, in addition to
licensing and other issues.

For this reason, a successful vaccine has not yet been
developed.
Malaria is an especially difficult disease to prevent
by vaccination because the parasite goes through several separate stages. One recent promising vaccine
appears to have protected up to 60% of people
exposed to malaria. This was evident during field trials
for the drug that were conducted in South America
and Africa. It is not yet commercially available.
The World Health Association (WHO) has been
trying to eliminate malaria for the past 30 years by
controlling mosquitoes. Their efforts were successful
as long as the pesticide DDT killed mosquitoes and
antimalarial drugs cured those who were infected.
Today, however, the problem has returned a hundredfold, especially in Africa. Because both the mosquito
and parasite are now extremely resistant to the insecticides designed to kill them, governments are now
trying to teach people to take antimalarial drugs as a
preventive medicine and avoid getting bitten by
mosquitoes.
A newer strategy as of late 2002 involves the
development of genetically modified non-biting mosquitoes. A research team in Italy is studying the feasibility of this means of controlling malaria.

A Western herb called wormwood (Artemesia
annua) that is taken as a daily dose can be effective
against malaria. Protecting the liver with herbs like
goldenseal (Hydrastis canadensis), Chinese goldenthread (Coptis chinensis), and milk thistle (Silybum
marianum) can be used as preventive treatment.
Preventing mosquitoes from biting you while in the
tropics is another possible way to avoid malaria.

Travelers to high-risk areas should use insect
repellant containing DEET for exposed skin.
Because DEET is toxic in large amounts, children
should not use a concentration higher than 35%.
DEET should not be inhaled. It should not be rubbed
onto the eye area, on any broken or irritated skin, or
on children’s hands. It should be thoroughly washed
off after coming indoors.

As of late 2002, researchers are studying a traditional African herbal remedy against malaria. Extracts
from Microglossa pyrifolia, a trailing shrub belonging
to the daisy family (Asteraceae), show promise in
treating drug-resistent strains of P. falciparum.

Those who use the following preventive measures
get fewer infections than those who do not:


Between dusk and dawn, remain indoors in wellscreened areas.



Sleep inside pyrethrin or permethrin repellentsoaked mosquito nets.



Wear clothes over the entire body.

Prognosis
If treated in the early stages, malaria can be cured.
Those who live in areas where malaria is epidemic,
however, can contract the disease repeatedly, never
fully recovering between bouts of acute infection.

Prevention
Several researchers are currently working on a
malarial vaccine, but the complex life cycle of the
malaria parasite makes it difficult. A parasite has
much more genetic material than a virus or bacterium.
2320

Anyone visiting endemic areas should take antimalarial drugs starting a day or two before they leave
the United States. The drugs used are usually chloroquine or mefloquine. This treatment is continued
through at least four weeks after leaving the endemic
area. However, even those who take antimalarial
drugs and are careful to avoid mosquito bites can
still contract malaria.
International travelers are at risk for becoming
infected. Most Americans who have acquired
GALE ENCYCLOPEDIA OF MEDICINE

Arteminisinins—A family of antimalarial products
derived from an ancient Chinese herbal remedy.
Two of the most popular varieties are artemether
and artesunate, used mainly in southeast Asia in
combination with mefloquine.
Chloroquine—An antimalarial drug that was first
used in the 1940s, until the first evidence of quinine
resistance appeared in the 1960s. It is now ineffective against falciparum malaria almost everywhere.
However, because it is inexpensive, it is still the
antimalarial drug most widely used in Africa.
Native individuals with partial immunity may
have better results with chloroquine than a traveler
with no previous exposure.
Mefloquine—An antimalarial drug that was developed by the United States Army in the early 1980s.
Today, malaria resistance to this drug has become a
problem in some parts of Asia (especially Thailand
and Cambodia).
Mefloquine—An antimalarial drug that was developed by the United States Army in the early 1980s.
Today, malaria resistance to this drug has become a
problem in some parts of Asia (especially Thailand
and Cambodia).
Quinine— One of the first treatments for malaria,
quinine is a natural product made from the bark of
the Cinchona tree. It was popular until being superseded by the development of chloroquine in the
1940s. In the wake of widespread chloroquine resistance, however, it has become popular again.
Quinine, or its close relative quinidine, can be given
intravenously to treat severe Falciparum malaria.
Sulfadoxone/pyrimethamine (Fansidar)—An antimalarial drug developed in the 1960s. It is the first
drug tried in some parts of the world where chloroquine resistance is widespread. It has been associated with severe allergic reactions due to its sulfa
component.

falciparum malaria were visiting sub-Saharan Africa;
travelers in Asia and South America are less at risk.
Travelers who stay in air conditioned hotels on tourist
itineraries in urban or resort areas are at lower risk
than backpackers, missionaries, and Peace Corps
volunteers. Some people in western cities where
malaria does not usually exist may acquire the infection from a mosquito carried onto a jet. This is called
airport or runway malaria.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Extraintestinal Protozoa: Malaria.’’ Section 13,
Chapter 161. In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Causer, Louise M, et al. ‘‘Malaria Surveillance—United
States, 2000.’’ Morbidity and Mortality Weekly Report
July 12, 2002: 9–15. Abstract.
Coluzzi, M., and C. Costantini. ‘‘An Alternative Focus in
Strategic Research on Disease Vectors: The Potential of
Genetically Modified Non-Biting Mosquitoes.’’
Parassitologia 44 (December 2002): 131–135.
‘‘Combination Approach Results in Significant Drop in
Malaria Rates in Viet Nam.’’ TB & Outbreaks Week
Abstract (September 24, 2002): 17.
Devi, G., V. A. Indumathi, D. Sridharan, et al. ‘‘Evaluation
of ParaHITf Strip Test for Diagnosis of Malarial
Infection.’’ Indian Journal of Medical Science 56
(October 2002): 489–494.
Keiser, J., J. Utzinger, Z. Premji, et al. ‘‘Acridine Orange for
Malaria Diagnosis: Its Diagnostic Performance, Its
Promotion and Implementation in Tanzania, and the
Implications for Malaria Control.’’ Annals of Tropical
Medicine and Parasitology 96 (October 2002): 643–654.
Kohler, I., K. Jenett-Siems, C. Kraft, et al. ‘‘Herbal
Remedies Traditionally Used Against Malaria in
Ghana: Bioassay-Guided Fractionation of Microglossa
pyrifolia (Asteraceae).’’ Zur Naturforschung 57
(November-December 2002): 1022–1027.
Krudsood, S., K. Buchachart, K. Chalermrut, et al.
‘‘A Comparative Clinical Trial of Combinations of
Dihydroartemisinin Plus Azithromycin and
Dihydroartemisinin Plus Mefloquine for Treatment of
Multidrug-Resistant Falciparum Malaria.’’ Southeast
Asian Journal of Tropical Medicine and Public Health 33
(September 2002): 525–531.
‘‘Laser-based Malaria Test could be Valuable.’’ Medical
Devices & Surgical Technology Week September 22,
2002: 4.
McClellan, S. L. ‘‘Evaluation of Fever in the Returned
Traveler.’’ Primary Care 29 (December 2002): 947–969.
‘‘Multilateral Initiative on Malaria to Move to Sweden.’’
TB & Outbreaks Week September 24, 2002: 17.
Noedl, H., C. Wongsrichanalai, R. S. Miller, et al.
‘‘Plasmodium falciparum: Effect of Anti-Malarial Drugs
on the Production and Secretion Characteristics of
Histidine-Rich Protein II.’’ Experimental Parasitology
102 (November-December 2002): 157–163.
‘‘Promising Vaccine May Provide Long-Lasting
Protection.’’ Medical Letter on the CDC & FDA
September 15, 2002: 14.
Stauffer, W. M., D. Kamat, and P. F. Walker. ‘‘Screening of
International Immigrants, Refugees, and Adoptees.’’
Primary Care 29 (December 2002): 879–905.
2321

Malaria

Resources

KEY TERMS

Malignant lymphomas

Thang, H. D., R. M. Elsas, and J. Veenstra. ‘‘Airport
Malaria: Report of a Case and a Brief Review of the
Literature.’’ Netherlands Journal of Medicine 60
(December 2002): 441–443.

develop from these two cell types. B cell lymphomas
are more common among adults, while among children, the incidence of T and B cell lymphomas are
almost equal.

ORGANIZATIONS

The T and the B cell perform different jobs within
the immune system. When an infectious bacterium
enters the body, the B cell makes proteins called ‘‘antibodies.’’ These antibodies attach themselves to the
bacteria, and flag them for destruction by other
immune cells. The T cells help protect the body against
viruses. When a virus enters the cell, it generally produces certain proteins that are projected on the surface
of the infected cell. T cells recognize these proteins and
produce certain substances (cytokines) that destroy
the infected cells. Some of the cytokines made by the
T cells attract other cell types, which are capable of
digesting the virus-infected cell. The T cells can also
destroy some types of cancerous cells.

Centers for Disease Control Malaria Hotline. (770)
332-4555.
Centers for Disease Control Travelers Hotline. (770)
332-4559.
OTHER

Malaria Foundation Page. <http://www.malaria.org>.

Carol A. Turkington
Rebecca J. Frey, PhD

Malaya see Elephantiasis
Male breast enlargement see Gynecomastia
Male condom see Condom
Male infertility see Infertility
Male pattern baldness see Alopecia

Malignant lymphomas
Definition
Lymphomas are a group of cancers in which cells
of the lymphatic system become abnormal and start to
grow uncontrollably. Because there is lymph tissue in
many parts of the body, lymphomas can start in
almost any organ of the body.

Description
The lymph system is made up of ducts or tubules
that carry lymph to all parts of the body. Lymph is a
milky fluid that contains the lymphocytes or white
blood cells. These are the infection-fighting cells of
the blood. Small pea-shaped organs are found along
the network of lymph vessels. These are called the
lymph nodes, and their main function is to make and
store the lymphocytes. Clusters of lymph nodes are
found in the pelvis region, underarm, neck, chest, and
abdomen. The spleen (an organ in the upper abdomen), the tonsils, and the thymus (a small organ found
beneath the breastbone) are part of the lymphatic
system.
The lymphocyte is the main cell of the lymphoid
tissue. There are two main types of lymphocytes: the
T lymphocyte and the B lymphocyte. Lymphomas
2322

Lymphomas can be divided into two main types:
Hodgkin’s lymphoma or Hodgkin’s disease, and nonHodgkin’s lymphomas. There are at least 10 types of
non-Hodgkin’s lymphomas. They are grouped
(staged) by how aggressively they grow; slow growing
(low grade), intermediate growing, and rapidly growing (high grade); and how far they spread.
A majority of non-Hodgkin’s lymphomas begin in
the lymph nodes. About 20% start in other organs,
such as the lungs, liver or the gastrointestinal tract.
Malignant lymphocytes multiply uncontrollably and
do not perform their normal functions. Hence, the
body’s ability to fight infections is affected. In addition, these malignant cells may crowd the bone marrow, and, depending on the stage, prevent the
production of normal red blood cells, white blood
cells, and platelets. A low red blood cell count causes
anemia, while a reduction in the number of platelets
makes the person susceptible to excessive bleeding.
Cancerous cells can also invade other organs through
the circulatory system of the lymph, causing those
organs to malfunction.

Causes and symptoms
The exact cause of non-Hodgkin’s lymphomas is
not known. However, the incidence has increased significantly in the recent years. Part of the increase is due
to the AIDS epidemic. Individuals infected with the
AIDS virus have a higher likelihood of developing
non-Hodgkin’s lymphomas. In general, males are at
a higher risk for having non-Hodgkin’s lymphomas
than are females. The risk increases with age. Though
it can strike people as young as 40, people between the
ages of 60 and 69 are at the highest risk.
GALE ENCYCLOPEDIA OF MEDICINE

There have been some studies that have shown a
loose association between retroviruses, such as
HTLV-I, and some rare forms of lymphoma. The
Epstein-Barr virus has been linked to Burkitt’s lymphoma in African countries. However, a direct causeand-effect relationship has not been established.
The symptoms of lymphomas are often vague and
non-specific. Patients may experience loss of appetite,
weight loss, nausea, vomiting, abdominal discomfort,
and indigestion. The patient may complain of a feeling
of fullness, which is a result of enlarged lymph nodes in
the abdomen. Pressure or pain in the lower back is
another symptom. In the advanced stages, the patient
may have bone pain, headaches, constant coughing,
and abnormal pressure and congestion in the face,
neck, and upper chest. Some may have fevers and
night sweats. In most cases, patients go to the doctor
because of the presence of swollen glands in the neck,
armpits, or groin area. Since all the symptoms are
common to many other illnesses, it is essential to
seek medical attention if any of the conditions persist
for two weeks or more. Only a qualified physician can
correctly diagnose if the symptoms are due to lymphoma or some other ailment.

Diagnosis
Like all cancers, lymphomas are best treated when
found early. However, it is often difficult to diagnose
lymphomas. There are no screening tests available, and,
since the symptoms are non-specific, lymphomas are
rarely recognized in their early stages. Detection often
occurs by chance during a routine physical examination.
When the doctor suspects lymphoma, a complete
medical history is taken, and a thorough physical
examination is performed. Enlargement of the lymph
nodes, liver, or spleen may suggest lymphomas. Blood
tests will determine the cell counts and obtain information on how well the organs, such as the kidney and
liver, are functioning.
A biopsy of the enlarged lymph node is the most
definitive diagnostic tool for staging purposes. The
GALE ENCYCLOPEDIA OF MEDICINE

Malignant lymphomas

People exposed to certain pesticides and ionizing
radiation have a higher than average chance of developing this disease. For example, an increased incidence
of lymphomas has been seen in survivors of the atomic
bomb explosion in Hiroshima, and in people who have
undergone aggressive radiation therapy. People who
suffer from immune-deficient disorders, as well as
those who have been treated with immune suppressive
drugs for heart or kidney transplants, and for conditions such as rheumatoid arthritis and autoimmune
diseases, are at an increased risk for this disease.

A malignant lymph cell. (Custom Medical Stock Photo.
Reproduced by permission.)

doctor may perform a bone marrow biopsy. During
the biopsy, a cylindrical piece of bone and marrow
fluid is removed. They are generally taken out of the
hipbone. These samples are sent to the laboratory for
examination. In addition to diagnosis, the biopsy may
also be repeated during the treatment phase of the
disease to see if the lymphoma is responding to
therapy.
Once the exact form of lymphoma is known, it is
then staged to determine how aggressive it is, and how
far it has spread. Staging is necessary to plan appropriate treatment.
Conventional imaging tests, such as x rays, computed tomography scans (CT scans), magnetic resonance imaging, and abdominal sonograms, are used
to determine the extent of spread of the disease.
Lymphangiograms are x rays of the lymphatic
system. In this procedure, a special dye is injected
into the lymphatic channels through a small cut (incision) made in each foot. The dye is injected slowly over
a period of three to four hours. This dye clearly outlines the lymphatic system and allows it to stand out.
Multiple x rays are then taken and any abnormality, if
present, is revealed.
Rarely, a lumbar puncture or a spinal tap is performed to check if malignant cells are present in the
fluid surrounding the brain. In this test, the physician
inserts a needle into the epidural space at the base of
the spine and collects a small amount of spinal fluid
for microscopic examination.

Treatment
Treatment options for lymphomas depend on the
type of lymphoma and its present stage. In most cases,
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Malignant lymphomas

treatment consists of chemotherapy, radiotherapy, or a
combination of the two methods.
Chemotherapy is the use of anti-cancer drugs to
kill cancer cells. In non-Hodgkin’s lymphomas, combination therapy, which involves the use of multiple
drugs, has been found more effective than single drug
use. The treatment may last about six months, but in
some cases may last as long as a year. The drugs may
either be administered intravenously (through a vein)
in the arm or given orally in the form of pills. If cancer
cells have invaded the central nervous system, then
chemotherapeutic drugs may be instilled, through a
needle in the brain or back, into the fluid that surrounds the brain. This procedure is known as intrathecal chemotherapy.
Radiation therapy, where high-energy ionizing
rays are directed at specific portions of the body,
such as the upper chest, abdomen, pelvis, or neck, is
often used for treatment of lymphomas. External
radiation therapy, where the rays are directed from a
source outside the body, is the most common mode of
radiation treatment.
Bone marrow transplantation is used in cases
where the lymphomas do not respond to conventional
therapy, or in cases where the patient has had a relapse
or suffers from recurrent lymphomas.
There are two ways of doing bone marrow transplantation. In a procedure called ‘‘allogeneic bone
marrow transplant,’’ a donor is found whose marrow
matches that of the patient. The donor can be a twin
(best match), a sibling, or a person who is not related
at all. High-dose chemotherapy or radiation therapy is
given to eradicate the lymphoma. The donor marrow
is then given to replace the marrow destroyed by the
therapy.
In ‘‘autologous bone marrow transplantation,’’
some of the patient’s own bone marrow is harvested,
chemically purged, and frozen. High-dose chemotherapy and radiation therapy are given. The marrow that
was harvested, purged, and frozen is then thawed and
put back into the patient’s body to replace the
destroyed marrow.
A new treatment option for patients with lymphoma is known as ‘‘peripheral stem cell transplantation.’’ In this treatment approach, cells that normally
circulate in the blood are collected when the patient
has normal blood counts taken, and these cells are
saved via a process called ‘‘pheresis.’’ Researchers
are exploring whether these cells can be used to restore
the normal function and development of blood cells,
rather than using a bone marrow transplant.
2324

KEY TERMS
Antibodies—Proteins made by the B lymphocytes
in response to the presence of infectious agents
such as bacteria or viruses in the body.
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Growth factors (cytokines)—Chemicals made by
the cells that act on other cells to stimulate or
inhibit their function. Cytokines that stimulate
growth are called ‘‘growth factors.’’

Prognosis
Like all cancers, the prognosis for lymphoma
depends on the stage of the cancer, and the patient’s
age and general health. When all the different types
and stages of lymphoma are considered together, only
50% of patients survive 5 years or more after initial
diagnosis. This is because some types of lymphoma are
more aggressive than others.
The survival rate among children is definitely better
than among older people. About 90% of the children
diagnosed with early stage disease survive 5 years or
more, while only 60-70% of adults diagnosed with low
grade lymphomas survive for 5 years or more. The
survival rate for children with the more advanced stages
is about 75-85%, while among adults it is 40-60%.

Prevention
Although many cancers may be prevented by
making diet and life style changes which reduce risk
factors, there is currently no known way to prevent
lymphomas. Protecting oneself from developing
AIDS, which may be a risk factor for lymphomas, is
the only preventive measure that can be practiced.
At present, there are no special tests that are available for early detection of non-Hodgkin’s lymphomas.
Paying prompt attention to the signs and symptoms of
this disease, and seeing a doctor if the symptoms persist,
are the best strategies for an early diagnosis of lymphoma. Early detection affords the best chance for a cure.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
GALE ENCYCLOPEDIA OF MEDICINE

OTHER

‘‘Adults Non-Hodgkin’s Lymphoma.’’ National Cancer
Institute Page. <http://www.nci.nih.gov>.
‘‘Childhood Non-Hodgkin’s Lymphoma.’’ National Cancer
Institute Page. <http://www.nci.nih.gov>.
‘‘Hodgkin’s Disease’’ and Non-Hodgkin’s Lymphoma.’’
The Leukemia Society. <http://www.leukemialymphoma.org/hm_lls>.

Lata Cherath, PhD

Malignant melanoma
Definition
Malignant melanoma is a type of cancer arising
from the melanocyte cells of the skin. Melanocytes are
cells in the skin that produce a pigment called melanin.
Malignant melanoma develops when the melanocytes
no longer respond to normal control mechanisms of
cellular growth. They may then invade nearby structures or spread to other organs in the body (metastasis), where again they invade and compromise the
function of that organ.

Description
Melanocytes are derived from a structure in the
human embryo called the neural crest. They are distributed in the epidermis and thus are found throughout the skin. They produce a brown pigment known as
melanin and are responsible for racial variation in skin
color as well as the color of moles. Malignant degeneration of the melanocyte gives rise to the tumor
known as melanoma, which has four subtypes. These
are: superficial spreading, nodular, lentigo maligna,
and acral lentiginous melanomas, accounting for
70%, 15% to 30%, 4% to 10%, and 2% to 8% of
cases, respectively. Malignant melanoma may develop
GALE ENCYCLOPEDIA OF MEDICINE

anywhere on the body. In men, it is most common on
the trunk. In women, it is most common on the back or
legs. The subtype also may influence where the tumor
develops; lentigo melanoma is more common on the
face while acral lentiginous melanoma is more common on the palms of the hand, soles of the feet, or in
the nail beds.
The locally invasive characteristic of this tumor
involves vertical penetration through the skin and into
the dermis and subcutaneous (under-the-skin) tissues
of the malignant melanocytes. With the exception of
the nodular variety of melanoma, there is often a
phase of radial or lateral growth associated with
these tumors. Since it is the vertical growth that characterizes the malignancy, the nodular variant of
melanoma carries the worst prognosis. Fortunately,
the superficial spreading type is most common.
The primary tumor begins in the skin, often from
the melanocytes of a pre-existing mole. Once it
becomes invasive, it may progress beyond the site of
origin to the regional lymph nodes or travel to other
organ systems in the body and become systemic in
nature.
Lymph is the clear, protein-rich fluid that bathes
the cells throughout our body. Lymph will work its
way back to the bloodstream via small channels
known as lymphatics. Along the way, the lymph is
filtered through cellular stations known as nodes,
thus they are called lymph nodes. Nearly all organs
in the body have a primary lymph node group filtering
the tissue fluid, or lymph, that comes from that organ.
Different areas of the skin have different primary
nodal stations. For the leg, they are in the groin. For
the arm, the armpit or axilla. For the face, it is the
neck. Depending where on the torso the tumor develops, it may drain into one groin or armpit, or both.
Cancer, as it invades in its place of origin, may
also work its way into blood vessels. If this occurs, it
provides yet another route for the cancer to spread to
other organs of the body. When the cancer spreads
elsewhere in the body, it has become systemic in extent
and the tumor growing elsewhere is known as a
metastasis.
Untreated malignant melanoma follows a classic
progression. It begins and grows locally, penetrating
vertically. It may be carried via the lymph to the
regional nodes, known as regional metastasis. It may
go from the lymph to the bloodstream or penetrate
blood vessels, directly allowing it a route to go elsewhere in the body. When systemic disease or distant
metastasis occur, melanoma commonly involves
the lung, brain, liver, or occasionally bone. The
2325

Malignant melanoma

Cancer Research Institute. 681 Fifth Ave., New York, N.Y.
10022. (800) 992-2623. <http://
www.cancerresearch.org>.
Leukemia Society of America, Inc. 600 Third Ave., New
York, NY 10016. (800) 955 4572. <http://
www.leukemia.org>.
Lymphoma Research Foundation. 8800 Venice Boulevard,
Suite 207, Los Angeles, CA 90034. (310) 204 7040.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
Oncolink. University of Pennsylvania Cancer Center.
<http://cancer.med.upenn.edu>.

Malignant melanoma

malignancy causes death when its uncontrolled growth
compromises vital organ function.

mutations occur at an early point in the development
of melanoma and remain as the tumor progresses.

Of the anticipated new cases of cancer for the year
2003 in the United States, malignant melanoma will
account for 5% of malignancies in men and 4% in
women, being the sixth most common cancer in men
and the seventh in women. It is estimated there will be
553,400 total cancer deaths in the United States in
2001. Malignant melanoma will account for 7,800 of
these deaths, for an incidence of 1.5% of total deaths
related to cancer.

As of early 2003, some researchers think there
may be two pathways to malignant melanoma, one
involving exposure to sunlight and the other with
melanocyte proliferation triggered by other factors.
This hypothesis is based on the difference in distribution of moles on the body between patients who
develop melanomas on the face and neck, and those
who develop melanomas on the trunk.

The incidence of primary cutaneous malignant
melanoma has been steadily increasing, possibly
related to increase of sun exposure. Currently, the
risk is about 13 per 100,000 of the population. It
affects all age groups but is most commonly seen in
patients between 30 and 60 years of age.
Sun exposure definitely increases the risk of developing melanoma, particularly in older males. The melanocytes are part of the integument’s photoprotective
mechanism; in response to sunlight, they produce
melanin that has a protective role from the sun’s ultraviolet rays. For Caucasians, the amount of melanin
present in the skin is directly related to sun exposure.
However, it is not so much the total sun exposure that
seems important, rather it is the history of sunburn,
(especially if severe or at an early age), that correlates
with the increased risk. On this basis populations of
fair-skinned people living in areas of high sun exposure such as the southwest United States or Australia
are subject to increased risk. Malignant melanoma
also affects non-Caucasians—though sun exposure
probably does not play a role—at a rate of 10% that
of Caucasians. The most common form of melanoma
in African Americans is acral lentiginous melanoma.
Malignant melanoma may arise in the skin anywhere on the body. It is estimated that 50%–70%
develop spontaneously while the remainder start in a
pre-existing mole.

Causes and symptoms
The predisposing causes to the development of
malignant melanoma are environmental and genetic.
The environmental factor is excessive sun exposure.
There are also genetically transmitted familial syndromes with alterations in the CDKN2A gene, which
encodes for the tumor-suppressing proteins p16 and
p19. In 2003 a group of Swedish researchers reported
that 63 out of a group of 71 melanoma patients, or
89% of the group, had mutations in either the NRAS
or the BRAF gene. The researchers found that these
2326

A small percentage of melanomas arise within
burn scar tissue. As of 2003, researchers do not fully
understand the relationship between deep burns and
an increased risk of skin cancer.
As mentioned previously, melanin production in
fair-skinned people is induced by sun exposure. An
exposure substantial enough to result in a mild sunburn will be followed by melanin producing a tan that
may last a few weeks. Both ultraviolet radiation and
damaging oxygen radicals caused by sun exposure
may damage cells, particularly their DNA. It is suspected that this damage induces mutations that result
in the development of malignant melanoma. Though
these mutations are alterations of the genome causing
the melanoma, they are environmentally induced and
account for sporadic or spontaneous cases of this
disease.
A positive family history of one or two first-degree
relatives having had melanoma substantially increases
the risk on a genetic basis. A family tendency is
observed in 8% to 12% of patients. There is a syndrome known as the dysplastic (atypical) nevus syndrome that is characterized by atypical moles with
bothersome clinical features in children under age 10.
Such individuals have to be observed closely for the
development of malignant melanoma. Chromosome
9p has been identified as being involved in familial
predisposition. There are mutations in up to 50% of
familial melanoma patients of the tumor-suppressing
gene CDKN2A. The actual number of moles increases
risk, but the size of the moles needs be considered.
Those with 10 larger moles of over 1 cm (0.4 in.) are
at more risk than those with a higher number (50-99)
of smaller moles. Finally, when a child is born with a
large congenital mole, careful observation for change
is appropriate because of increased risk.
An excellent way of identifying changes of significance in a mole is the ABCDE rule:


Asymmetry



Border irregularity



Color variegation
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Diameter greater than 6 mm (0.24 in)



Elevation above surrounding tissue.

Malignant melanoma



Notice that three of the criteria refer to variability
of the lesion (color variegation refers to areas of light
color and black scattered within the mole). Thus small,
uniform regular lesions have less cause for concern. It
is important to realize that change in a mole or the
rapid development of a new one are very important
symptoms.
Another summary of important changes in a mole
is the Glasgow 7-point scale. The symptoms and signs
below can occur anywhere on the skin, including the
palms of the hands, soles of the feet, and also the nail
beds:


Change in size



Change in shape



Change in color



Inflammation



Crusting and bleeding



Sensory change



Diameter greater than 7 mm (0.28 in.

In this scheme, change is emphasized along with
size. Bleeding and sensory changes are relatively late
symptoms.
Symptoms related to the presence of regional disease are mostly those of nodules or lumps in the areas
containing the lymph nodes draining the area. Thus
nodularity can be found in the armpit, the groin, or the
neck if regional nodes are involved. There is also a
special type of metastasis that can occur regionally
with malignant melanoma; it is known as an in-transit
metastasis. If the melanoma is spreading through the
lymph system, some of the tumor may grow there,
resulting in a nodule part way between the primary
site and the original lymph node. These in-transit
metastasis are seen both at the time of original presentation or later after primary treatment has been
rendered, the latter being a type of recurrence.
Finally, in those who either present with or progress to widespread or systemic disease, symptoms and
signs are related to the affected organ. Thus neurologic problems, lung problems, or liver problems
develop depending on the organ involved.

Diagnosis
None of the clinical signs or symptoms discussed
above are absolute indications that a patient has
malignant melanoma. The actual diagnosis is
GALE ENCYCLOPEDIA OF MEDICINE

A close-up image of a malignant melanoma on a patient’s
back. (Custom Medical Stock Photo. Reproduced by permission.)

accomplished by biopsy, a procedure that removes
tissue to examine under a microscope. It is important
that the signs and symptoms are used to develop a
suspicion of the diagnosis because the way the biopsy
is performed for melanoma may be different than for
other lesions of the skin.
The doctor may also use a dermatoscope to examine the mole prior to removal. The dermatoscope,
which can be used to distinguish between benign
moles and melanomas, is an instrument that resembles
an ophthalmoscope. An immersion oil is first applied
to the mole to make the outer layers of skin
transparent.
When dealing with an early malignant melanoma,
it is very important to establish the exact thickness of
penetration of the primary tumor. Any biopsy that
does not remove the full vertical extent of the primary
is inadequate. Therefore, if a skin lesion is suspicious,
full thickness excisional biopsy is the approach
2327

Malignant melanoma

recommended. Shave biopsies and biopsies that
remove only a portion of the suspect area are inappropriate. Often, in an early case, the excision involves
just the suspicious lesion with minimal normal skin,
but it should be a full vertical excision of the skin. If a
melanoma is diagnosed, further treatment of this area
will often be necessary but does not compromise outcome (prognosis). In some special areas of the body,
minor modifications may be necessary about initial
total excision, but full thickness excision should
always be the goal. (See staging, below.)
Once the diagnosis is obtained, careful examination of the patient for regional lymph node involvement should be done. A careful review to uncover any
symptoms of widespread disease is also appropriate.
The more common patient has an early melanoma, and extensive testing is not usually warranted.
Routine testing in this situation involves a complete
blood count, a chest x ray, and determinations of blood
enzymes including lactic dehydrogenase and alkaline
phosphatase.
If the patient has signs or symptoms of more
advanced disease, or if the lesion’s depth of penetration is sizeable, further imaging studies may be appropriate. These would involve CAT scans of the
abdomen, the chest, or regional nodal areas, or a CT
or MRI of the brain.

Treatment
The key to successful treatment is early diagnosis.
Patients identified with localized, thin, small lesions
(typified by superficial spreading subtype) nearly
always survive. For those with advanced lesions, the
outcome is poor in spite of progress in systemic
therapy.
Clinical staging
Malignant melanoma is locally staged based on
the depth of penetration through the skin and its
appendages. There are two ways of looking at the
depth of penetration. The Clarke system utilizes the
layers of the dermis and the skin appendages present at
that layer to identify the depth of penetration. The
Breslow system uses the absolute measurement of
depth. Though useful conceptually, the Clarke system
is used less frequently because of the fact that skin is of
different thickness in different regions of the body.
The depth of penetration is much greater when the
tumor reaches the subcutaneous fat when the skin
involved is the back as opposed to the face. It turns
out that the Breslow measurement is more
2328

reproducible and thus more useful; therefore, for purposes here, depth of penetration by absolute measurement (Breslow) is used in local staging.
Stage I and stage II have no involvement of the
regional lymph nodes and are thus localized to the site
of origin. These stages are subdivided on the basis of
penetration. Stage Ia is 0.75 mm or less (1 mm = 0.04
in), and Stage Ib is 0.75–1.5 mm penetration. Stage IIa
is 1.5–4.0 mm and Stage IIb is over 4.0 mm or into the
subcutaneous fat. In stage III and IV, there is disease
beyond the primary site. Stage III is defined by the
presence of in-transit or regional nodal metastasis or
both. Stage IV is defined by the presence of distant
metastasis.
Once the diagnosis of malignant melanoma has
been established by biopsy and the stage has been
identified using the results of the examination and
studies, a treatment plan is developed. Melanoma is
not cured unless it is diagnosed at a stage when it can
be isolated and removed surgically. Considerations
revolve around the extent of the local and regional
nodal surgery for stages I through III. For stage IV
patients, or those that are treated and then develop
recurrence at distant sites, chemotherapy or immunotherapy is planned. Studies are in progress to
improve the results from traditional chemotherapeutic
regimens. Adjuvant therapy (auxiliary drug treatment
used to make possibility of relapse less for those at
high risk) is also considered.
Surgical therapy for the primary site is that of
wide local removal of the skin including subcutaneous
tissue surrounding the lesion. In the past, wide excisions were large and encompassed 2 in. of tissue in all
directions wherever feasible. It has been shown that
such wide local excisions are not necessary and the
issue has become: how wide is enough? Studies from
the World Health Organization Melanoma Group
and by the Melanoma Intergroup Committee in the
United States have provided general guidelines based
on the depth of penetration of the melanoma. These
guidelines and anatomic considerations need to be
kept in mind by the surgeon.
The next issue in primary management is whether
the patient should have the regional lymph nodes
removed in addition to treatment of the primary
tumor. The problems associated with the resection
of regional lymph nodes are those of lifelong edema
or swelling in the extremity. Though it does not occur
in all patients (5% to 20%, depending on the extremity and extent of the dissection), it can be a disabling symptom. Certainly, if it could be ascertained
that there was disease in the nodes, resection
GALE ENCYCLOPEDIA OF MEDICINE

Questions related to which patients should have
resection of regional lymph nodes have led to an intermediary procedure known as sentinel node mapping
and biopsy. Intermediate thickness melanomas
between 1 and 4 mm deep (0.04 and 0.16 in.) may
have nodal involvement even if the examination and
any other studies done are normal. If a radioisotope
tracer or blue dye is injected into the area of the
primary tumor, very shortly it will travel to the
lymph nodes draining that area. These sentinel nodes
are thus identifiable and are the most likely to harbor
any regional metastatic disease. If these nodes alone
are biopsied and are normal, the rest of the lymph
node group can be spared. If they show microscopic
deposits of tumor, then the full resection of the lymph
node group may be completed. This procedure allows
selection of those patients with intermediate thickness
melanoma who will benefit from the regional lymph
node dissection.
Patients with metastatic melanoma who do not
respond well to other therapies may be candidates
for treatment with aldesleukin. Aldesleukin is a form
of interleukin, a specific kind of biological response
modifier that promotes the development of T-cells.
These cells are part of the lymphatic system and can
directly interact with and fight cancer cells. Although
aldesleukin is produced naturally in the body, its
therapeutic form is developed via biotechnology in a
laboratory setting. Treatment is considered palliative,
which means that it provides comfort but does not
produce a cure. Side effects, however, can be severe,
and range from flu-like symptoms to whole-body
infection (sepsis) and coma.
Some patients, such as those with IIb or stage III
melanoma, are at high risk for the development of
recurrence after treatment. Although these patients
are clinically free of disease after undergoing primary
GALE ENCYCLOPEDIA OF MEDICINE

treatment, they are more likely to have some microscopic disease in the body that studies have not yet
been able to identify. In an effort to decrease the rate
of relapse, adjuvant therapy may be considered.
Interferon alpha 2a is an agent that stimulates the
immune system. This adjuvant therapy may slightly
increase the duration of a patient’s disease-free state
and lengthen overall survival. However, interferon
alpha 2a has high toxicity and patients may not tolerate the side effects.
Unfortunately, treatment for those patients who
present with or go on to develop systemic disease
usually fails; melanoma that has metastasized to the
brain is particularly difficult to treat. The chemotherapeutic agent dacarbazine, or DTIC, seems to be the
most active agent. Overall responses are noted in
about 20% of patients, and they last only two to six
months. Combination therapy may be an option. The
regimen of DTIC + BCNU (carmustine) + cisplatin +
tamoxifen delivers a response rate of 40%. Combining
biologic or immunologic agents such as interferon
with standard chemotherapeutic agents is under
study and showing improved response rates, though
toxicity is substantial and only the healthier, younger
patients tolerate the treatment.
Some researchers are investigating the reasons
why melanomas are so resistant to chemotherapy.
One suggestion as of late 2003 is that the genes ordinarily responsible for apoptosis (cell self-destruction)
do not function normally in melanomas. The development of new drugs to treat melanoma depends on a
better understanding of the complex processes
involved in apoptosis.

Alternative treatment
Though radiation therapy has a minimal role
in the primary treatment of malignant melanoma,
for patients who have metastatic disease, radiation
may be helpful. This is true in patients who have
developed tumor deposits in such areas as the brain
or bone.

Prognosis
Almost all patients survive stage Ia malignant
melanoma, and the suvivorship for stage I overall is
more than 90%. Survival drops in stage IIa to about
65% at five years and is worse yet for stage IIb at
slightly over 50%. Stage III has a survival rate at
5 years of 10%–47%, depending on the size and number of regional nodes involved. Stage IV malignant
melanoma is almost always a fatal disease.
2329

Malignant melanoma

(removal) would be appropriate. However, if there
was no disease, the risk of edema should be avoided.
In patients with no signs of regional disease, depth of
penetration of the primary tumor helps guide the
decision. If the tumor penetrates less than 1mm, dissection is not usually done. If it is 1-2 mm, node
dissection may be done at the time of primary treatment or the patient may be observed and only
undergo lymph node dissection if the area later
shows signs of disease. If the patient has enlarged
lymph nodes or the depth of the tumor has led to
the evaluation by CAT scan showing enlarged nodes,
resection of the nodes will be considered. In the latter
case, more extensive imaging of the lung, liver, or
brain may be appropriate to be sure the patient does
not already have stage IV disease.

Malignant melanoma

KEY TERMS
Adjuvant therapy—Treatment given to patients
who are at risk of having microscopic untreated
disease present but have no obvious symptoms.
Dermis—The deeper portion or layer of the skin
beneath the epidermis.
Dysplastic nevus syndrome—A familial syndrome
characterized by the presence of multiple atypical
appearing moles, often at a young age.
Epidermis—The uppermost layer of skin cells.
Genome—The genetic makeup of a cell, composed
of DNA.
Immunotherapy—A form of treatment that uses
biologic agents to enhance or stimulate normal
immune function.
Integument—The medical name for the skin.
Lymph node dissection—Surgical removal of a
group of lymph nodes.
Lymphedema—Swelling of an arm or leg following
surgical removal of the lymph nodes that drain the
limb.
Melanocytes—Skin cells derived from the neural
crest that produce the protein pigment melanin.
Metastasis (plural, metastases)—A tumor growth
or deposit that has spread via lymph or blood to
an area of the body remote from the primary tumor.
Nevus (plural, nevi)—A medical term for mole.
Resection—The act of removing something
surgically.
Skin appendages—Structures related to the integument such as hair follicles and sweat glands.
Variegation—Patchy variation in color.

Coping with cancer treatment
For those with familial tendencies for malignant
melanoma, genetic counseling may be appropriate.
Psychological counseling may be appropriate for anyone having trouble coping with a potentially fatal
disease. Local cancer support groups may be helpful
and are often identified by contacting local hospitals
or the American Cancer Society.

Prevention
Though it is difficult to prove that sunscreens
statistically reduce the frequency of malignant
2330

melanoma at this time, most authorities recommend
their use as protection from ultraviolet light (considered a major factor in the development of melanoma.)
Avoidance of severe sunburns is recommended.
Resources
BOOKS

Abeloff, Armitage, Lichter, and Niederhuber. Clinical
Oncology Library. 2nd ed. London: Churchill
Livingstone, 1999.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Dermatologic Disorders: Malignant Tumors.’’
Section 10, Chapter 126. In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Dermatologic Disorders: Moles.’’ Section 10, Chapter
125 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Dermatologic Disorders: Reactions to Sunlight.’’
Section 10, Chapter 119. In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Brown, C. K., and J. M. Kirkwood. ‘‘Medical Management
of Melanoma.’’ Surgical Clinics of North America 83
(April 2003): 283–322.
Carlson, J. A., A. Slominski, G. P. Linette, et al.
‘‘Malignant Melanoma 2003: Predisposition,
Diagnosis, Prognosis, and Staging.’’ American Journal
of Clinical Pathology 120 , Supplement (December
2003): S101–S127.
Eigentler, T. K., U. M. Caroli, P. Radny, and C. Garbe.
‘‘Palliative Therapy of Disseminated Malignant
Melanoma: A Systematic Review of 41 Randomised
Clinical Trials.’’ Lancet Oncology 4 (December 2003):
748–759.
Halder, R. M., and C. J. Ara. ‘‘Skin Cancer and Photoaging
in Ethnic Skin.’’ Dermatologic Clinics 21 (October
2003): 725–732.
Horig, H., and H. L. Kaufman. ‘‘Local Delivery of Poxvirus
Vaccines for Melanoma.’’ Seminars in Cancer Biology
13 (December 2003): 417–422.
Jellouli-Elloumi, A., L. Kochbati, S. Dhraief, et al. ‘‘Cancers
Arising from Burn Scars: 62 Cases.’’ [in French] Annales
de dermatologie et de venereologie 130 (April 2003):
413–416.
McWilliams, R. R., P. D. Brown, J. C. Buckner, et al.
‘‘Treatment of Brain Metastases from Melanoma.’’
Mayo Clinic Proceedings 78 (December 2003):
1529–1536.
Omholt, K., A. Platz, L. Kanter, et al. ‘‘NRAS and BRAF
Mutations Arise Early During Melanoma Pathogenesis
and Are Preserved Throughout Tumor Progression.’’
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050.
<http://www.aad.org>.
American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800) ACS-2345.
National Cancer Institute (NCI). NCI Public Inquiries
Office, Suite 3036A, 6116 Executive Boulevard,
MSC8332, Bethesda, MD 20892-8322. (800)
4-CANCER or (800) 332-8615 (TTY).
<http://www.nci.nih.gov>.

can also help them obtain financial compensation
through insurance claims, lawsuits, or workers’ compensation. Feigned symptoms may also be a way of
getting the doctor to prescribe certain drugs.
According to the American Psychiatric
Association, patients who malinger are different
from people who invent symptoms for sympathy
(factitious diseases). Patients who malinger clearly
have something tangible to gain. People with factitious
diseases appear to have a need to play the ‘‘sick’’ role.
They may feign illness for attention or sympathy.
Malingering may take the form of complaints of
chronic whiplash pain from automobile accidents.
Whiplash claims are controversial. Although some
people clearly do suffer from whiplash injury, others
may be exaggerating the pain for insurance claims or
lawsuits. Some intriguing scientific studies have shown
that chronic whiplash pain after automobile accidents
is almost nonexistent in Lithuania and Greece. In
these countries, the legal systems do not encourage
personal injury lawsuits or financial settlements. The
psychological symptoms experienced by survivors of
disaster (post-traumatic stress disorder) are also faked
by malingerers.

OTHER

Cancer Resource Center. American Cancer Society. June 20,
2001. <http://www3.cancer.org/cancerinfo>.
Melanoma Patient’s Information Page. June 20, 2001.
<http://www.mpip.org>.
National Cancer Institute. June 13, 2001. <http://rex.nci.
nih.gov/PATIENTS/INFO_PEOPL_DOC.html>.

Richard A. McCartney, MD
Rebecca J. Frey, PhD

Malignant plasmacytoma see Multiple
myeloma

Causes and symptoms
People malinger for personal gain. The symptoms
may vary. Generally malingerers complain of psychological disorders such as anxiety. They may also complain of chronic pain for which objective tests such as
x rays can find no physical cause. Because it is often
impossible to determine who is malingering and
who is not, it is impossible to know how frequently
malingering occurs.

Diagnosis
Malingering may be suspected:

Malingering



When a patient is referred for examination by an
attorney



When the onset of illness coincides with a large
financial incentive, such as a new disability policy



When objective medical tests do not confirm the
patient’s complaints



When the patient does not cooperate with the diagnostic work-up or prescribed treatment



When the patient has antisocial attitudes and behaviors (antisocial personality).

Definition
In the context of medicine, malingering is the act
of intentionally feigning or exaggerating physical or
psychological symptoms for personal gain.

Description
People may feign physical or psychological illness
for any number of reasons. Faked illness can get them
out of work, military duty, or criminal prosecution. It
GALE ENCYCLOPEDIA OF MEDICINE

The diagnosis of malingering is a challenge
for doctors. On the one hand, the doctor does not
2331

Malingering

Clinical Cancer Research 9 (December 15, 2003):
6483–6488.
Rockmann, H., and D. Schadendorf. ‘‘Drug Resistance in
Human Melanoma: Mechanisms and Therapeutic
Opportunities’’ Onkologie 26 (December 2003):
581–587.
Weinstock, Martin A. ‘‘Early Detection of Melanoma.’’
JAMA, The Journal of the American Medical
Association 284 (August 16, 2000): 886.
Whiteman, D. C., P. Watt, D. M. Purdie, et al.
‘‘Melanocytic Nevi, Solar Keratoses, and Divergent
Pathways to Cutaneous Melanoma.’’ Journal of
the National Cancer Institute 95 (June 4, 2003):
806–812.

Mallet finger

KEY TERMS
Antisocial personality—A personality characterized by attitudes and behaviors at odds with
society’s customs and moral standards, including
illegal acts.
Factitious diseases—Conditions in which symptoms are deliberately manufactured by patients
in order to gain attention and sympathy. Patients
with factitious diseases do not fake symptoms
for obvious financial gain or to evade the legal
system.
Post traumatic stress disorder (PTSD)—A disorder
that occurs among survivors of severe environmental stress such as a tornado, an airplane crash, or
military combat. Symptoms include anxiety,
insomnia, flashbacks, and nightmares. Patients
with PTSD are unnecessarily vigilant; they may
experience survivor guilt, and they sometimes cannot concentrate or experience joy.

want to overlook a treatable disease. On the other
hand, he or she does not want to continue ordering
tests and treatments if the symptoms are faked.
Malingering is difficult to distinguish from certain
legitimate personality disorders, such as factitious diseases or post-traumatic distress syndrome. In legal
cases, malingering patients may be referred to a
psychiatrist. Psychiatrists use certain written tests to
try to determine whether the patient is faking the
symptoms.

Treatment
In a sense, malingering cannot be treated
because the American Psychiatric Association does
not recognize it as a personality disorder. Patients
who are purposefully faking symptoms for gain do
not want to be cured. Often, the malingering patient
fails to report any improvement with treatment,
and the doctor may try many treatments without
success.

Definition
Mallet finger refers to the involuntary flexion of
the distal phalanx of a finger caused by the disruption
or tearing of its extensor tendon.

Description
Tendons are the strong ‘‘cables’’ between muscles
and bones that help control movements of the body.
They consist of white, glistening, fibrous cords, of
various length and thickness, either round or flattened,
and lacking in elasticity. In mallet finger, which often
occurs as a sports-related injury, the tendon on the
back of the finger becomes damaged or torn near the
outermost joint. Without the support provided by
the tendon, the short bone at the tip of the finger drops
downward at an awkward angle. This bone, referred to
as the ‘‘distal phalanx’’ of a finger, is the one furthest
from the palm. In addition to tendon damage, mallet
finger may involve a fracture of the distal phalanx.
Mallet finger is sometimes called baseball finger.

Causes and symptoms
Mallet finger usually occurs while playing a sport
that involves a ball—for example, reaching out to
catch a hard pass in basketball or bare-handing a
baseball. Instead of landing on the palm of the hand,
the ball accidentally hits the tip of an extended (or
partially extended) finger. This straight-on impact
causes instantaneous stretch of the tendon, which
may overextend or tear away. Mallet finger can also
result from hitting the hand against a hard object or
receiving a cut from a sharp edge such as a knife.
Symptoms of mallet finger include pain and
swelling around the top part of the finger, near the
outermost joint. These symptoms occur right after the
injury. Redness and swelling develop soon afterward.
The tip of the finger has an abnormal-looking
downward droop, and it may be difficult to fully
extend the finger.

Diagnosis

Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924.
<http://www.psych.org>.

Robert Scott Dinsmoor
2332

Mallet finger

Mallet finger is usually diagnosed after a relatively
brief physical examination conducted by an emergency
care physician or by an orthopedist, the type of doctor
who specializes in such injuries. The downward droop
of the fingertip is the major indication of mallet finger,
along with the tenderness and pain that occurs in the
GALE ENCYCLOPEDIA OF MEDICINE

Distal Phalanx—The outermost bone of any finger
or toe.
Fracture—A break in bone.
Orthopedist—A doctor who specializes in disorders of the musculoskeletal system.
Phalanx—Any of the digital bones of the hand or
foot. Humans have three phalanges to each finger
and toe with the exception of the thumb and big toe
which have only two each.
Tendon—A tough cord of dense white fibrous connective tissue that connects a muscle with some
other part, especially a bone, and transmits the
force which the muscle exerts.

affected area. X rays will be taken to determine if the
bone at the top of the finger has been fractured. Mallet
finger is typically covered by medical insurance.

Treatment

With proper treatment, most people regain full
use of the affected finger.

Prevention
Caution should be used when playing ball sports
or using knives or other sharp implements.
Resources
BOOKS

Brukner, Peter, et al. Clinical Sports Medicine: McGrawHill, 2000.
PERIODICALS

Lester, B., et al. ‘‘A simple effective splinting technique for
the mallet finger.’’ American Journal of Orthopedics
March 2000: 202-6.
Takami H, et al. ‘‘Operative treatment of mallet finger due to
intra-articular fracture of the distal phalanx.’’ Archives
of Orthopaedic and Trauma Surgery 120 (2000): 9-13.
ORGANIZATIONS

American Academy of Orthopaedic Surgeons. 6300 North
River Road, Rosemont, IL 60018-4262. (800)
346-AAOS. <http://www.aaos.org>.

Greg Annussek

If symptoms of mallet finger appear, the affected
individual should consult a physician or seek emergency care. In the meantime, ice (wrapped in a towel or
cloth) can be applied to the affected area to help
reduce swelling and alleviate pain.
Treatment usually involves wearing a splint
around the top of the affected finger in order to keep
it extended and allow the injury to heal. The splint
must be worn at all times for six to eight weeks, though
it may be briefly removed to wash the finger, but with
extreme care so as not to allow the fingertip to bend.
For the next six to eight weeks after that, the splint
need only be worn during sleep or athletic activities.
If the bone at the top of the finger has sustained a
large fracture, surgery may necessary. If the tendon was
damaged due to a cut, stitches may be required both to
repair the tendon and to adequately close the wound.
Over-the-counter (OTC) or prescription pain
medication can be used to alleviate pain.

Alternative treatment
Acupuncture, therapeutic massage, and yoga are
believed by some practitioners of alternative medicine
to have generalized pain-relieving effects. Any of these
therapies may provide additional comfort while the
finger heals.
GALE ENCYCLOPEDIA OF MEDICINE

Mallory-Weiss syndrome
Definition
Mallory-Weiss syndrome is bleeding from an
arterial blood vessel in the upper gastrointestinal
tract, caused by a mucosal gastric tear at or near the
point where the esophagus and stomach join.

Description
Mallory-Weiss syndrome causes about 5% of all
upper gastrointestinal bleeding. The condition was
originally diagnosed in alcoholics and is associated
with heavy alcohol use, although it can also be found
in patients who are not alcoholics. Earlier episodes of
heavy hiccupping, vomiting, and retching are reported
by about half the patients who are diagnosed with
Mallory-Weiss syndrome. It is thought that the tear
or laceration occurs when there is a sudden increase in
intra-abdominal pressure. Patients with increased
pressure in the vein leading into the liver (portal hypertension) are more likely to bleed heavily from an
2333

Mallory-Weiss syndrome

Prognosis

KEY TERMS

Malnutrition

KEY TERMS
Electrolytes—Salts and minerals that can conduct
electrical impulses in the body. Common human
electrolytes are sodium chloride, potassium, calcium, and sodium bicarbonate. Electrolytes control
the fluid balance of the body and are important in
muscle contraction, energy generation, and almost
every major biochemical reaction in the body.
Endoscopy—A procedure in which an instrument
containing a camera and a light source is inserted
into the gastrointestinal tract so that the doctor can
visually inspect the gastrointestinal system.
Esophageal varix—An enlarged vein of the esophagus. (Plural: esophageal varices.)
Portal hypertension —High blood pressure in the
portal vein, which carries blood from the abdominal organs to the liver.

esophageal bleeding stops spontaneously. When
bleeding does not stop, patients are treated with an
injection of epinephrine (adrenaline) and/or the bleeding artery is cauterized with heat. If these treatments
fail, surgery is performed to stop the bleeding.

Prognosis
In 90-95% of patients whose bleeding does not
stop spontaneously, cauterization without surgery will
stop the bleeding. Patients at highest risk for a recurrence of bleeding are those with portal hypertension.

Prevention
Mallory-Weiss syndrome is associated with alcoholism. Limiting alcohol intake may help prevent the
disorder.
Resources
BOOKS

esophageal laceration than those whose blood pressure is normal.

‘‘Mallory-Weiss Syndrome.’’ In Current Medical Diagnosis
and Treatment, 1998. edited by Stephen McPhee, et al.,
37th ed. Stamford: Appleton & Lange, 1997.

Tish Davidson, A.M.

Causes and symptoms
In Mallory-Weiss syndrome, a tear occurs in the
gastric mucosa, near where the esophagus and stomach join. About 10% of the tears are in the esophagus. Most are either right at the junction of the
esophagus and stomach or in the stomach just slightly
below the junction.
Bleeding from the tear causes a disruption in fluid
and electrolyte balance of the body. The patient often
produces vomit tinged with either fresh blood or older,
blackish blood. Blood loss can be considerable.

Diagnosis
A Mallory-Weiss syndrome tear is not visible on
standard upper gastrointestinal x rays. A tear about
one-eighth to one and one-half inches long (0.5–4 cm)
is revealed by endoscopy. Endoscopy also shows that
in 35% of patients there is another potential cause for
gastrointestinal bleeding, such as peptic ulcer, erosive
gastritis, or esophageal varices.

Treatment
The patient is resuscitated and stabilized with
blood transfusions and intravenous fluids to restore
the fluid and electrolyte balance. Most of the time,
2334

Malnutrition
Definition
Malnutrition is the condition that develops when
the body does not get the right amount of the vitamins,
minerals, and other nutrients it needs to maintain
healthy tissues and organ function.

Description
Undernutrition
Malnutrition occurs in people who are either
undernourished or overnourished. Undernutrition is
a consequence of consuming too few essential nutrients or using or excreting them more rapidly than they
can be replaced.
Infants, young children, and teenagers need additional nutrients. So do women who are pregnant or
breastfeeding. Nutrient loss can be accelerated by diarrhea, excessive sweating, heavy bleeding (hemorrhage), or kidney failure. Nutrient intake can be
restricted by age-related illnesses and conditions,
GALE ENCYCLOPEDIA OF MEDICINE

The leading cause of death in children in developing countries is protein-energy malnutrition. This
type of malnutrition is the result of inadequate
intake of calories from proteins, vitamins, and
minerals. Children who are already undernourished
can suffer from protein-energy malnutrition (PEM)
when rapid growth, infection, or disease increases
the need for protein and essential minerals. These
essential minerals are known as micronutrients or
trace elements.
Two types of protein-energy malnutrition have
been described—kwashiorkor and marasmus.
Kwashiorkor occurs with fair or adequate calorie
intake but inadequate protein intake, while marasmus
occurs when the diet is inadequate in both calories and
protein.
About 1% of children in the United States suffer
from chronic malnutrition, in comparison to 50% of
children in southeast Asia. About two-thirds of all the
malnourished children in the world are in Asia, with
another one-fourth in Africa.
Overnutrition
In the United States, nutritional deficiencies have
generally been replaced by dietary imbalances or
excesses associated with many of the leading causes
of death and disability. Overnutrition results from
eating too much, eating too many of the wrong things,
not exercising enough, or taking too many vitamins or
other dietary replacements.
Risk of overnutrition is also increased by being
more than 20% overweight, consuming a diet high in
fat and salt, and taking high doses of:


Nicotinic acid (niacin) to lower elevated cholesterol
levels



Vitamin B6 to relieve premenstrual syndrome



Vitamin A to clear up skin problems



Iron or other trace minerals not prescribed by a
doctor.

Nutritional disorders can affect any system in the
body and the senses of sight, taste, and smell. They
may also produce anxiety, changes in mood, and other
psychiatric symptoms. Malnutrition begins with
changes in nutrient levels in blood and tissues.
Alterations in enzyme levels, tissue abnormalities,
and organ malfunction may be followed by illness
and death.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Causes
Poverty and lack of food are the primary reasons
why malnutrition occurs in the United States. Ten
percent of all members of low income households do
not always have enough healthful food to eat. Proteinenergy malnutrition occurs in 50% of surgical patients
and in 48% of all other hospital patients.
Loss of appetite associated with the aging process.
Malnutrition affects one in four elderly Americans, in
part because they may lose interest in eating. In addition, such dementing illnesses as Alzheimer’s disease
may cause elderly persons to forget to eat.
There is an increased risk of malnutrition associated with chronic diseases, especially disease of the
intestinal tract, kidneys, and liver. Patients with
chronic diseases like cancer, AIDS, intestinal parasites, and other gastric disorders may lose weight
rapidly and become susceptible to undernourishment
because they cannot absorb valuable vitamins, calories, and iron.
People with drug or alcohol dependencies are also
at increased risk of malnutrition. These people tend to
maintain inadequate diets for long periods of time and
their ability to absorb nutrients is impaired by the
alcohol or drug’s affect on body tissues, particularly
the liver, pancreas, and brain.
Eating disorders. People with anorexia or bulimia
may restrict their food intake to such extremes that
they become malnourished.
Food allergies. Some people with food allergies
may find it difficult to obtain food that they can digest.
In addition, people with food allergies often need
additional calorie intake to maintain their weight.
Failure to absorb nutrients in food following bariatric (weight loss) surgery. Bariatric surgery includes
such techniques as stomach stapling (gastroplasty)
and various intestinal bypass procedures to help people eat less and lose weight. Malnutrition is, however,
a possible side effect of bariatric surgery.
Symptoms
Unintentionally losing 10 pounds or more may be
a sign of malnutrition. People who are malnourished
may be skinny or bloated. Their skin is pale, thick, dry,
and bruises easily. Rashes and changes in pigmentation are common.
Hair is thin, tightly curled, and pulls out easily.
Joints ache and bones are soft and tender. The gums
bleed easily. The tongue may be swollen or shriveled
2335

Malnutrition

excessive dieting, food allergies, severe injury, serious
illness, a lengthy hospitalization, or substance abuse.

Malnutrition

and cracked. Visual disturbances include night blindness and increased sensitivity to light and glare.
Other symptoms of malnutrition include:

inflammatory bowel disease. This procedure involves
inserting a thin tube through the nose and carefully
guiding it along the throat until it reaches the stomach
or small intestine. If long-term tube feeding is necessary, the tube may be placed directly into the stomach
or small intestine through an incision in the abdomen.



anemia



diarrhea



disorientation



night blindness



irritability, anxiety, and attention deficits



Are severely malnourished



goiter (enlarged thyroid gland)



Require surgery



loss of reflexes and lack of muscular coordination



Are undergoing
treatments



muscle twitches


Have been seriously burned



amenorrhea (cessation of menstrual periods)


Have persistent diarrhea or vomiting



scaling and cracking of the lips and mouth.


Whose gastrointestinal tract is paralyzed.

Malnourished children may be short for their age,
thin, listless, and have weakened immune systems.

Tube feeding cannot always deliver adequate
nutrients to patients who:

Blood and urine tests are used to measure the
patient’s levels of vitamins, minerals, and waste products. Nutritional status can also be determined by:


Comparing a patient’s weight to standardized charts



Calculating body mass index (BMI) according to a
formula that divides height into weight



Measuring skinfold thickness or the circumference of
the upper arm.

Patients who cannot or will not eat, or who are
unable to absorb nutrients taken by mouth, may be fed
intravenously (parenteral nutrition) or through a tube
inserted into the gastrointestinal (GI) tract (enteral
nutrition).
Tube feeding is often used to provide nutrients to
patients who have suffered burns or who have
2336

radiation

Prognosis
Up to 10% of a person’s body weight can be lost
without side effects, but if more than 40% is lost, the
situation is almost always fatal. Death usually results
from heart failure, electrolyte imbalance, or low body
temperature. Patients with semiconsciousness, persistent diarrhea, jaundice, or low blood sodium levels
have a poorer prognosis.
Some children with protein-energy malnutrition
recover completely. Others have many health problems throughout life, including mental retardation
and the inability to absorb nutrients through the
intestinal tract. Prognosis for all patients with malnutrition seems to be dependent on the age of the patient,
and the length and severity of the malnutrition, with
young children and the elderly having the highest rate
of long-term complications and death.

Treatment
Normalizing nutritional status starts with a nutritional assessment. This process enables a clinical nutritionist or registered dietician to confirm the presence
of malnutrition, assess the effects of the disorder, and
formulate diets that will restore adequate nutrition.

or

Intravenous feeding can supply some or all of the
nutrients these patients need.

Diagnosis
Overall appearance, behavior, body-fat distribution, and organ function can alert a family physician,
internist, or nutrition specialist to the presence of malnutrition. Patients may be asked to record what they
eat during a specific period. X rays can determine bone
density and reveal gastrointestinal disturbances, and
heart and lung damage.

chemotherapy

Prevention
Breastfeeding a baby for at least six months is
considered the best way to prevent early-childhood
malnutrition. The United States Department of
Agriculture and Health and Human Service recommend that all Americans over the age of two:


Consume plenty of fruits, grains, and vegetables



Eat a variety of foods that are low in fats and cholesterols and contain only moderate amounts of salt,
sugars, and sodium



Engage in moderate physical activity for at least
30 minutes, at least several times a week
GALE ENCYCLOPEDIA OF MEDICINE

Anemia—Not enough red blood cells in the blood.
Anorexia nervosa—Eating disorder marked by malnutrition and weight loss commonly occurring in
young women.
Bariatric—Pertaining to the study, prevention, or
treatment of overweight.
Calorie—A unit of heat measurement used in nutrition to measure the energy value of foods. A calorie
is the amount of heat energy needed to raise the
temperature of 1 kilogram of water 18C.
Kwashiorkor—Severe malnutritution in children
primarily caused by a protein-poor diet, characterized by growth retardation.
Marasmus—Severe malnutritution in children
caused by a diet lacking in calories as well as
protein. Marasmus may also be caused by disease
and parasitic infection.
Micronutrients—Essential dietary elements that
are needed only in very small quantities.
Micronutrients are also known as trace elements.
They include copper, zinc, selenium, iodine, magnesium, iron, cobalt, and chromium.

Amella, E. J. ‘‘Feeding and Hydration Issues for Older
Adults with Dementia.’’ Nursing Clinics of North
America 39 (September 2004): 607–623.
Bryan, J., S. Osendorp, D. Hughes, et al. ‘‘Nutrients
for Cognitive Development in School-Aged
Children.’’ Nutrition Reviews 62 (August 2004):
295–306.
Grigsby, Donna G., MD. ‘‘Malnutrition.’’ eMedicine
December 18, 2003. <http://www.emedicine.com/ped/
topic1360.htm>.
Gums, J. G. ‘‘Magnesium in Cardiovascular and Other
Disorders.’’ American Journal of Health-System
Pharmacy 61 (August 1, 2004): 1569–1576.
Halsted, G. H. ‘‘Nutrition and Alcoholic Liver
Disease.’’ Seminars in Liver Disease 24 (August 2004):
289–304.
Reid, C. L. ‘‘Nutritional Requirements of Surgical and
Critically-Ill Patients: Do We Really Know What They
Need?’’ Proceedings of the Nutrition Society 63 (August
2004): 467–472.
ORGANIZATIONS

American College of Nutrition. 722 Robert E. Lee Drive,
Wilmington, NC 20412-0927. (919) 452-1222.
American Institute of Nutrition. 9650 Rockville Pike,
Bethesda, MD 20814-3990. (301) 530-7050.
Food and Nutrition Information Center. 10301 Baltimore
Boulevard, Room 304, Beltsville, MD 20705-2351.
<http://www.nalusda.gov/fnic>.
OTHER



Achieve or maintain their ideal weight



Use alcohol sparingly or avoid it altogether.

World Health Organization (WHO) Nutrition web site.
<http://www.who.int/nut/index.htm>.

Mary K. Fyke
Rebecca J. Frey, PhD

Every patient admitted to a hospital should be
screened for the presence of illnesses and conditions
that could lead to protein-energy malnutrition.
Patients with higher-than-average risk for malnutrition should be more closely assessed and reevaluated
often during long-term hospitalization or nursinghome care.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Malnutrition.’’ Section 1, Chapter 2. In The Merck
Manual of Diagnosis and Therapy.Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Flancbaum, Louis, MD, with Erica Manfred and Deborah
Biskin. The Doctor’s Guide to Weight Loss Surgery.
West Hurley, NY: Fredonia Communications, 2001.
PERIODICALS

Alvarez-Leite, J. I. ‘‘Nutrient Deficiencies Secondary to
Bariatric Surgery.’’ Current Opinion in Clinical
Nutrition and Metabolic Care 7 (September 2004):
569–575.
GALE ENCYCLOPEDIA OF MEDICINE

Malocclusion
Definition
Malocclusion is a problem in the way the upper
and lower teeth fit together in biting or chewing. The
word malocclusion literally means ‘‘bad bite.’’ The
condition may also be referred to as an irregular bite,
crossbite, or overbite.

Description
Malocclusion may be seen as crooked, crowded,
or protruding teeth. It may affect a person’s appearance, speech, and/or ability to eat.
2337

Malocclusion

KEY TERMS

Malocclusion

Causes and symptoms
Malocclusions are most often inherited, but may
be acquired. Inherited conditions include too many or
too few teeth, too much or too little space between
teeth, irregular mouth and jaw size and shape, and
atypical formations of the jaws and face, such as a
cleft palate. Malocclusions may be acquired from
habits like finger or thumb sucking, tongue thrusting,
premature loss of teeth from an accident or dental
disease, and medical conditions such as enlarged
tonsils and adenoids that lead to mouth breathing.
Malocclusions may be symptomless or they may
produce pain from increased stress on the oral structures. Teeth may show abnormal signs of wear on the
chewing surfaces or decay in areas of tight overlap.
Chewing may be difficult.

Diagnosis
Malocclusion is most often found during a routine dental examination. A dentist will check a
patient’s occlusion by watching how the teeth make
contact when the patient bites down normally. The
dentist may ask the patient to bite down with a piece
of coated paper between the upper and lower teeth;
this paper will leave colored marks at the points of
contact. When malocclusion is suspected, photographs and x rays of the face and mouth may be
taken for further study. To confirm the presence
and extent of malocclusion, the dentist makes plaster,
plastic, or artificial stone models of the patient’s
teeth from impressions. These models duplicate the
fit of the teeth and are very useful in treatment
planning.

Treatment
Malocclusion may be remedied by orthodontic
treatment; orthodontics is a specialty of dentistry
that manages the growth and correction of dental
and facial structures. Braces are the most commonly
used orthodontic appliances in the treatment of malocclusion. At any given time, approximately 4 million
people in the United States are wearing braces, including 800,000 adults.
Braces apply constant gentle force to slowly
change the position of the teeth, straightening them
and properly aligning them with the opposing teeth.
Braces consist of brackets cemented to the surface of
each tooth and wires of stainless steel or nickel titanium alloy. When the wires are threaded through the
brackets, they exert pressure against the teeth, causing
them to move gradually.
2338

Orthodontia treatments usually include the use of braces and
retainers. (Photograph by Lester V. Bergman, Corbis Images.
Reproduced by permission).

Braces are not removable for daily tooth brushing, so the patient must be especially diligent about
keeping the mouth clean and removing food particles
which become easily trapped, to prevent tooth decay.
Foods that are crunchy should be avoided to minimize
the risk of breaking the appliance. Hard fruits, vegetables, and breads must be cut into bite-sized pieces
before eating. Foods that are sticky, including chewing
gum, should be avoided because they may pull off the
brackets or weaken the cement. Carbonated beverages
may also weaken the cement, as well as contribute to
tooth decay. Teeth should be brushed immediately
after eating sweet foods. Special floss threaders are
available to make flossing easier.
If overcrowding is creating malocclusion, one or
more teeth may be extracted (surgically removed),
giving the others room to move. If a tooth has not
yet erupted or is prematurely lost, the orthodontist
may insert an appliance called a space maintainer to
keep the other teeth from moving out of their natural
position. In severe cases of malocclusion, surgery
may be necessary and the patient would be referred
to yet another specialist, an oral or maxillofacial
surgeon.
Once the teeth have been moved into their new
position, the braces are removed and a retainer is worn
until the teeth stabilize in that position. Retainers do
not move teeth, they only hold them in place.
GALE ENCYCLOPEDIA OF MEDICINE

Braces—An orthodontic appliance consisting or
brackets cemented to the surface of each tooth
and wires of stainless steel or nickel titanium
alloy. Braces are used to treat malocclusion by
changing the position of the teeth.
Impression—An imprint of the upper or lower teeth
made in a pliable material that sets. When this
material has hardened, it may be filled with plaster,
plastic, or artificial stone to make an exact model of
the teeth.
Occlusion—The way the upper and lower teeth fit
together in biting or chewing.
Retainer—An orthodontic appliance that is worn to
stabilize teeth in a new position.

This patient’s teeth are misarranged because of excessive
thumb sucking. (Custom Medical Stock Photo. Reproduced by
permission.)

Space maintainer—An orthodontic appliance that is
worn to prevent adjacent teeth from moving into the
space left by an unerupted or prematurely lost tooth.

Prevention
Orthodontic treatment is the only effective treatment for malocclusion not requiring surgery.
However, depending on the cause and severity of the
condition, an orthodontist may be able to suggest
other appliances as alternatives to braces.

Alternative treatment
There are some techniques of craniosacral therapy
that can alter structure. This therapy may allow correction of some cases of malocclusion. If surgery is
required, pre- and post-surgical care with homeopathic remedies, as well as vitamin and mineral supplements, can enhance recovery. Night guards are
sometimes recommended to ease the strain on the
jaw and to limit teeth grinding.

In general, malocclusion is not preventable. It
may be minimized by controlling habits such as finger
or thumb sucking. An initial consultation with an
orthodontist before a child is 7 years old may lead to
appropriate management of the growth and development of the child’s dental and facial structures,
circumventing many of the factors contributing to
malocclusion.
Resources
ORGANIZATIONS

American Association of Oral and Maxillofacial Surgeons.
9700 West Bryn Mawr Ave., Rosemont, IL 60018-5701.
(847) 678-6200. <http://www.aaoms.org>.
American Association of Orthodontists. 401 North
Lindbergh Boulevard, St. Louis, MO 63141-7816. (314)
993-1700. <http://www.aaortho.org>.

Prognosis
Depending on the cause and severity of the malocclusion and the appliance used in treatment, a
patient may expect correction of the condition to
take 2 or more years. Patients typically wear braces
18-24 months and a retainer for another year.
Treatment is faster and more successful in children
and teens whose teeth and bones are still
developing. The length of treatment time is also
affected by how well the patient follows orthodontic
instructions.
GALE ENCYCLOPEDIA OF MEDICINE

Bethany Thivierge

MALT lymphoma
Definition
MALT lymphomas are solid tumors that originate from cancerous growth of immune cells that are
2339

MALT lymphoma

KEY TERMS

MALT lymphoma

recruited to secretory tissue such as the gastrointestinal tract, salivary glands, lungs, and the thyroid
gland.

Description
The digestive tract is generally not associated with
lymphoid tissue, with the exception of small collections of lymphocytes such as Peyer’s patches. A specific kind of white blood cell, B-lymphocytes, can
accumulate in response to infections of the digestive
tract and other secretory tissues, or as a result of
autoimmune conditions such as Sjgren’s syndrome.
When the growth of these lymphocytes is maintained
through continued infection or autoimmune disease,
a malignant cell can arise and replace the normal
lymphocytes. These lymphomas, derived from
mucosa-associated lymphoid tissue (MALT), most
commonly arise in the stomach. Their growth seems
to be dependent upon continuous stimulation of the
immune system by an infectious agent, such as
H. pylori, or some other entity, termed an antigen,
that the body recognizes as foreign. This antigen-driven
growth permits these tumors to be treated by eliminating the stimulus that generated the original, normal
immune response. In the stomach they are associated,
in greater than 90% of all cases, with the bacteria called
Helicobacter pylori (H. pylori). This bacteria is also
associated with peptic stomach irritation, ulcers, and
gastric cancer. MALT lymphomas are generally indolent, that is, they grow slowly and cause little in the way
of symptoms. Those MALT lymphomas that arise in
the stomach in response to H. pylori infections are
generally successfully treated with antibiotics, which
eliminate the bacteria.

Demographics
MALT lymphomas occur at a frequency of about
1.5 per 100,000 people per year in the United States
and account for about 10% of all non-Hodgkin’s
lymphomas. The frequency varies among different
populations. For example, in parts of Italy the
frequency of MALT lymphomas is as high as 13 per
100,000 people per year. This can in part be attributed
to different rates of infection with H. pylori. However,
other hereditary, dietary, or environmental factors are
almost certainly involved.

Causes and symptoms
The majority of MALT lymphomas appear to
be the result of infectious agents, most commonly
H. pylori in the stomach. It is not known if infectious
agents also cause MALT lymphomas outside of the
2340

stomach. In some cases, such as in the thyroid,
MALT lymphomas seem to arise in patients who
have autoimmune diseases, which make their immune
systems treat their own tissue as foreign or antigenic. It
is believed that there must be additional factors, in
addition to infection or autoimmunity, that influence
the development of MALT lymphomas. For example,
in the United States, where infections with H. pylori
are quite common, less than 1 in 30,000 people who
have H. pylori in their stomachs develop MALT
lymphomas. In addition, individuals who develop
MALT lymphomas are more likely to develop other
forms of cancer. This would suggest that there might
be genetic factors predisposing individuals to develop
MALT lymphomas or other tumors in response to
environmental or infectious agents.
In general, patients have stomach pain, ulcers, or
other localized symptoms, but rarely do they suffer
from systemic complaints such as fatigue or fever.

Diagnosis
The indolent nature of most MALT lymphomas
means that the majority of patients are diagnosed at
early stages with relatively nonspecific symptoms. In
the case of gastric MALT lymphomas, the physician
will then have a gastroenterologist perform an endoscopy to examine the interior of the stomach. MALT
lymphomas are then recognized as areas of inflammation or ulceration within the stomach. It is unusual
for masses recognizable as tumors to be seen upon
examination. Definitive diagnosis of MALT lymphoma requires a biopsy, in which a bit of tissue is
removed from the stomach or other involved site.
Examination of this tissue by a pathologist is the first
step in distinguishing among the possible diagnoses of
inflammation, indolent lymphoma, or a more aggressive form of cancer, such as gastric cancer or a rapidly
growing non-Hodgkin’s lymphoma. The pathologist
evaluates the type of lymphoid cells that are present in
the biopsy to establish the nature of the lesion. In
addition, it is essential that the pathologist determine
whether or not the lymphoma has grown beyond the
borders of the mucosa, which lines the stomach or
other gland.

Treatment
The best staging system to employ for MALT
lymphomas is still the subject of discussion.
However, it is standard practice that patients presenting with MALT lymphomas should be evaluated in a
similar manner to individuals with nodal lymphomas,
the more common type of lymphoma that originates at
GALE ENCYCLOPEDIA OF MEDICINE

In general, the prognosis for patients with
MALT lymphomas is good, with overall five-year
survival rates that are greater than 80%. The features
that are most closely related to the outlook for
newly diagnosed individual patients are: whether
the primary site is in the stomach or is extra-gastric;
if the disease has spread beyond the initial location;
and whether the histologic evaluation of the initial
tumor biopsies is consistent with a low-grade, slowly
growing lesion, as compared to a high-grade
lesion that is more rapidly growing. In general, the
histologic grade is the most important feature, with
high-grade lesions requiring the most aggressive
treatment.
Treatment of MALT lymphomas differs from
that of most lymphomas. In the most common type
of MALT lymphomas—low-grade lesions originating
in the stomach—treatment with antibiotics to eliminate H. pylori leads to complete remissions in the
majority of patients. The effectiveness of this treatment is indistinguishable from surgery, chemotherapy,
radiation therapy, or a combination of surgery with
drugs or irradiation. Approximately one-third of
patients in this group have evidence of disseminated
disease, where lymphoma cells are detected at sites in
addition to the gastric mucosa. The response of these
patients to antibiotic treatment is not significantly
different from that for individuals with localized disease. For both groups a complete remission is achieved
in about 75% of patients, who remain, on average, free
of disease for about 5 years.

Prognosis
Patients with MALT lymphomas arising outside
of the digestive tract also have good prognoses.
Effective treatment for these lymphomas has been
achieved with local radiation, chemotherapy, and/or
interferon. Surgery followed by chemotherapy or
radiation is also effective with nongastrointestinal
MALT lymphomas. Overall these patients have fiveyear survival rates greater than 90%.
While the outlook for patients with MALT lymphomas is good, difficulties in diagnosis and staging
have left the optimal treatment a matter of continued
study. This is an especially open question for those
patients who fail to respond to antibiotic therapy, or
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Antigen—A foreign substance that leads to an
immune response, including the production of antibodies by B cells.
Autoimmune disease—A condition in which an
individual’s immune system reacts to their own
tissues, viewing self components as if they were
foreign antigens.
Bone marrow biopsy—A procedure in which cellular material is removed from the pelvis or breastbone and examined under a microscope to look for
the presence of abnormal blood cells characteristic
of specific forms of leukemia and lymphoma.
Indolent lymphoma (also called low-grade)—
Cancerous growths of lymphoid tissue that progress
slowly to more aggressive forms of cancer.
Lymphoid tissue—Sites within the body that produce cells of the immune system, including lymph
nodes, bone marrow, and the thymus.

whose disease recurs. It may be the case that in these
patients, the MALT lymphoma may have already
progressed to a point where high-grade lesions, not
observed in the original biopsies, were resistant to the
initial treatment. The best treatment for these patients
remains to be established. IN general, these patients
are treated with chemotherapy in a similar manner to
patients with other types of lymphoma. Given the
success of antibiotics, and the good prognosis for
gastric MALT lymphomas in general, no sufficient
body of evidence exists to determine the best chemotherapy for patients who fail to achieve a complete
and lasting remission upon initial treatment. At present, a chemotherapeutic regime designated CHOP
includes the anti-cancer drugs cyclophosphamide,
doxorubicin, vincristine, and prednisone. Similar
drug combinations are being used for patients whose
MALT lymphomas do not respond to antibiotic
treatment.
Clinical trials are underway and mostly concentrate upon optimizing treatment of gastric MALT
lymphomas that involve H. pylori. The aspects of
treatment being addressed are the most effective antibiotics and the use of antacids to modulate irritation
in the stomach. These protocols have been designed
to follow the natural history of gastric lymphomas
and to establish the biological features that predict
treatment response to antibiotics and duration of
remission.
2341

MALT lymphoma

sites within the lymphoid system. These procedures
include a complete history and physical, blood tests,
chest x rays, and bone marrow biopsy. This evaluation
will permit the oncologist to determine if the disease is
localized or if it has spread to other sites within the
body.

Mammography

Prevention
There are currently no commonly accepted means
to prevent MALT lymphomas. While the H. pylori
infections are associated with this and other gastric
disease, the eradication of H pylori in asymptomatic
individuals is not currently recommended for prevention of MALT lymphomas or gastric cancer.
Resources
PERIODICALS

Thieblemont, C., et al. ‘‘Mucosa-associated Lymphoid
Tissue Lymphoma is a Disseminated Disease in
One-third of 158 Patients Analyzed.’’ Blood 95
(February 2000): 802-6.
Zucca, E., et al. ‘‘The Gastric Marginal Zone Lymphoma of
MALT Type.’’ Blood 96 (July 2000): 410-19.
OTHER

‘‘Low-Grade Non-Hodgkin’s Lymphoma: A Year 2000
Perspective.’’ Medscape. June 2000. <http://
www.medscape.com/medscape/oncology/
clinicalmgmt/CM.v03/public/index-CM.v03.html>.

Warren Maltzman, Ph.D.

Malta fever see Brucellosis
Mammogram screening see Mammography

Mammography
Definition
Mammography is the study of the breast using
x ray. The actual test is called a mammogram. There
are two types of mammograms. A screening mammogram is ordered for women who have no problems with
their breasts. It consists of two x-ray views of each
breast. A diagnostic mammogram is for evaluation of
new abnormalities or of patients with a past abnormality requiring follow-up (i.e., a woman with breast cancer
treated with lumpectomy). Additional x rays from other
angles or special views of certain areas are taken.

Purpose
The purpose of screening mammography is breast
cancer detection. A screening test, by definition, is
used for patients without any signs or symptoms in
order to detect disease as early as possible. Many
studies have shown that having regular mammograms
increases a woman’s chances of finding breast cancer
in an early stage, when it is more likely to be curable. It
2342

has been estimated that a mammogram may find a
cancer as much as two years before it can be felt. The
American Cancer Society, American College of
Radiology, American College of Surgeons and
American Medical Association recommend annual
mammograms for every woman beginning at age 40.
Screening mammograms usually are not recommended for women under age 40 who have no special
risk factors and a normal physical breast examination.
Below age 40, breasts tend to be ‘‘radiographically
dense,’’ which means it is difficult to see many details.
In 2003, a new technique that introduces radiographic
contrast into digital mammograms was proving useful
at improving visibility of breast cancer in younger
women. Screening mammograms can detect cancers
in their earliest stages and greatly reduce mortality,
particularly among women age 40 to 69. In fact, a
study in 2003 found that women age 40 and older
who had annual screening mammograms had better
breast cancer prognoses because their cancers were
diagnosed at earlier stages than women who had
mammograms less often.
Some women are at increased risk for developing
breast cancer, such as those with two or more relatives
who have the disease. The 2003 American Cancer
Society guidelines stated that women at increased
risk might benefit from earlier screening mammograms and more frequent intervals for screening.
However, the society suggested that evidence was not
strong enough at that time to support making specific
recommendations concerning screening examinations.
Diagnostic mammography is used to evaluate an
existing problem, such as a lump, discharge from the
nipple, or unusual tenderness in one area. The cause of
the problem may be definitively diagnosed from this
study, but further investigation using other methods
often is necessary. This exam also is used to evaluate
findings from screening mammography.

Description
A mammogram may be offered in a variety of
settings. Hospitals, outpatient clinics, physicians’
offices, or other facilities may have mammography
equipment. In the United States, since October 1,
1994, only places certified by the U.S. Food and
Drug Administration (FDA) are legally permitted to
perform, interpret, or develop mammograms under
the Mammography Quality Standards Act (MQSA).
In addition to the usual paperwork, a woman will
be asked to fill out a form seeking information
relevant to her risk of breast cancer and special
GALE ENCYCLOPEDIA OF MEDICINE

The mammogram may be seen and interpreted by a
radiologist right away, or it may not be reviewed until
later. If there are any questionable areas or an abnormality, extra x rays may be recommended. These may be
taken during the same appointment. More commonly,
especially for screening mammograms, the woman is
called back on another day for these additional films.
A screening mammogram usually takes approximately 15 to 30 minutes. A woman having a diagnostic
mammogram can expect to spend up to an hour at the
mammography facility.

A person undergoing a mammography. (Custom Medical
Stoch Photo Inc. Reproduced by permission)

mammography needs. The woman is asked about
personal and family history of cancer, details about
menstruation, child bearing, birth control, breast
implants, other breast surgery, age, and hormone
replacement therapy. Information about Breast Self
Examination (BSE) and other breast health issues
usually are available at no charge.
At some centers, a technologist may perform a
physical examination of the breasts before the mammogram. Whether or not this is done, it is essential for
the patient to tell the technologist about any lumps,
nipple discharge, breast pain, or other concerns.
Clothing from the waist up is removed and a
hospital gown or similar covering is put on. The
woman stands facing the mammography machine.
The technologist exposes one breast and places it on
a plastic or metal film holder about the size of a
placemat. The breast is compressed as flat as possible
between the film holder and a rectangle of plastic
(called a paddle), which presses down onto the breast
from above. The compression should only last a few
seconds, just enough to take the x ray. Good compression can be uncomfortable, but it is necessary to
ensure the clearest view of all breast tissues.
GALE ENCYCLOPEDIA OF MEDICINE

The cost of mammography varies widely. Many
mammography facilities accept ‘‘self referral.’’ This
means women can schedule themselves without a physician’s referral. However, some insurance policies
require a doctor’s prescription to ensure payment.
Medicare will pay for annual screening mammograms
for all women with Medicare who are age 40 or older
and a baseline mammogram for those age 35 to 39.
A digital mammogram is performed in the same
way as a traditional exam, but the image is viewed on a
computer monitor, stored as a digital file, and can be
printed on film. Medicare now pays a small additional
fee for digital mammography.

Preparation
The compression or squeezing of the breast for a
mammogram is a concern for some women, but necessary to render a quality image. Even with concerns
about pain, a 2003 study said that three-fourths of
women reported the pain associated with a mammogram as four on a 10-point scale. Mammograms
should be scheduled when a woman’s breasts are
least likely to be tender. One week after the menstrual
period is usually best. The MQSA regulates equipment
compression for consistency and performance.
Women should not put deodorant, powder, or
lotion on their upper body on the day the mammogram is performed. Particles from these products can
get on the breast or film holder and may look like
abnormalities on the mammogram film.
2343

Mammography

Next, the woman is positioned with her side
toward the mammography unit. The film holder is
tilted so the outside of the breast rests against it, and
a corner touches the armpit. The paddle again holds
the breast firmly as the x ray is taken. This procedure is
repeated for the other breast. A total of four x rays,
two of each breast, are taken for a screening mammogram. Additional x rays, using special paddles, different breast positions, or other techniques are usually
taken for a diagnostic mammogram.

Mammography

KEY TERMS
Breast biopsy—A procedure in which suspicious
tissue is removed and examined by a pathologist for
cancer or other disease. The breast tissue may be
obtained by open surgery or through a needle.
Radiographically dense—Difficult to see details of
breast tissue on x ray.

the mammogram is incomplete and requires further
assessment.
Comparison of two mammograms—cancerous tissue is
shown on left and normal tissue on right. (Custom Medical
Stock Photo. Reproduced by permission.)

Aftercare
No special aftercare is required.

Risks
The risk of radiation exposure from a mammogram is considered virtually nonexistent. Experts are
unanimous that any negligible risk is far outweighed
by the potential benefits of mammography.
Some breast cancers do not show up on mammograms, or ‘‘hide’’ in dense breast tissue. A normal (or
negative) study is not a guarantee that a woman is
cancer-free. Mammograms find about 85% to 90%
of breast cancers.
‘‘False positive’’ readings also are possible, and
5% to 10% of mammogram results indicate the need
for additional testing, most of which confirm that no
cancer is present.

Normal results
A mammography report describes details about
the x ray appearance of the breasts. It also rates the
mammogram according to standardized categories, as
part of the Breast Imaging Reporting and Data
System (BIRADS) created by the American College
of Radiology (ACR). A normal mammogram may be
rated as BIRADS 1 or negative, which means no
abnormalities were seen. A normal mammogram
may also be rated as BIRADS 2 or benign findings.
This means that one or more abnormalities were
found but are clearly benign (not cancerous), or variations of normal. Some kinds of calcification, lymph
nodes, or implants in the breast might generate a
BIRADS 2 rating. A BIRADS 0 rating indicates that
2344

Abnormal results
Many mammograms are considered borderline or
indeterminate in their findings. BIRADS 3 means an
abnormality is present and probably (but not definitely) benign. A follow-up mammogram within a
short interval of six months is suggested. This helps
to ensure that the abnormality is not changing, or is
‘‘stable.’’ This stability in the abnormality indicates
that a cancer is probably not present. If the abnormality is cancerous, it will likely grow and change in the
time between mammograms. Some women are
uncomfortable or anxious about waiting and may
want to consult with their doctor about having a
biopsy. BIRADS 4 means suspicious for cancer. A
biopsy is usually recommended in this case. BIRADS
5 means an abnormality is highly suggestive of cancer.
The suspicious area should be biopsied.
Often, screening mammograms are followed up
with additional imaging. The reasons are numerous;
they may mot mean the radiologist suspects a cancerous lesion, only that he or she cannot make a clear
diagnosis from the screening mammogram views. The
most common imaging methods are additional views
on the mammogram, sometimes called magnification
views, and ultrasound. In recent years, some patients
have received magnetic resonance imaging (MRI) of
the breast. A new technique called dual-energy contrast enhanced digital subtraction mammography
is reported to find cancers that may be missed by
conventional mammography. It may be ordered in
the future as a follow-up study.
Resources
BOOKS

Henderson, Craig. Mammography & Beyond. Developing
Technologies for the Early Detection of Breast Cancer:
A Non-technical Summary. Washington, DC: National
Academy Press, 2001.
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

‘‘Contrast Mammography Reveals Hard-to-find Cancers.’’
Cancer Weekly October 14, 2003: 34.
‘‘Mammography in Women Over Forty Catches Disease
Earlier.’’ Women’s Health Weekly August 14, 2003: 14.
‘‘New Digital Technique Improves Mammography
Results.’’ Women’s Health Weekly September 18,
2003: 28.
Smith, Robert A., et al. ‘‘American Cancer Society
Guidelines for Breast Cancer Screening: Update 2003.’’
Cancer May-June 2003: 141-170.
‘‘Stress—Not Pain— Is Major Barrier to Mammography.’’
Contemporary OB/GYN July 2003: 17.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., Atlanta, GA
30329. (800) ACS-2345. <http://www.cancer.org>.
National Cancer Institute. Office of Cancer
Communications, Bldg. 31, Room 10A31, Bethesda,
MD 20892. NCI/Cancer Information Service: (800)
4-CANCER. <http://cancernet.nci.nih.gov>.
U.S. Food and Drug Administration. 5600 Fishers Lane,
Rockville, MD 20857. (800) 532-4440.
<http://www.fda.gov>.

sleep. (Note: Hypomania is a term applied to a condition resembling mania. It is characterized by persistent
or elevated expansive mood, hyperactivity, inflated
self esteem, etc., but of less intensity than mania.)
Severe mania may have psychotic features.

Causes and symptoms
Mania can be induced by the use or abuse of
stimulant drugs such as cocaine and amphetamines.
It is also the predominant feature of bipolar disorder,
or manic depression, an affective mental illness that
causes radical emotional changes and mood swings.
The Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (DSM-IV), the diagnostic
standard for mental health professionals in the U.S.,
describes a manic episode as an abnormally elevated
mood lasting at least one week that is distinguished by
at least three of the following symptoms: inflated selfesteem, decreased need for sleep, talkativeness, racing
thoughts, distractibility, increase in goal-directed
activity, or excessive involvement in pleasurable activities that have a high potential for painful consequences. If the mood of the patient is irritable and
not elevated, four of these symptoms are required.

Ellen S. Weber, MSN
Teresa G. Odle

Manganese excess see Mineral toxicity

Mania
Definition
Mania is an abnormally elated mental state, typically characterized by feelings of euphoria, lack of
inhibitions, racing thoughts, diminished need for
sleep, talkativeness, risk taking, and irritability. In
extreme cases, mania can induce hallucinations and
other psychotic symptoms.

Diagnosis
Mania is usually diagnosed and treated by a
psychiatrist and/or a psychologist in an outpatient setting. However, most severely manic patients require
hospitalization. In addition to an interview, several
clinical inventories or scales may be used to assess the
patient’s mental status and determine the presence and
severity of mania. An assessment commonly includes
the Young Mania Rating Scale (YMRS). The MiniMental State Examination (MMSE) may also be given
to screen out other illnesses such as dementia.

Treatment
Mania is primarily treated with drugs. The following mood-stabilizing agents are commonly prescribed
to regulate manic episodes:


Lithium (Cibalith-S, Eskalith, Lithane) is one of the
oldest and most frequently prescribed drugs available for the treatment of mania. Because the drug
takes four to seven days to reach a therapeutic level
in the bloodstream, it is sometimes prescribed in
conjunction with neuroleptics (antipsychotic drugs)
and/or benzodiazepines (tranquilizers) to provide
more immediate relief of mania.



Carbamazepine (Tegretol, Atretol) is an anticonvulsant drug usually prescribed in conjunction with other

Description
Mania typically occurs as a symptom of bipolar
disorder (a mood disorder characterized by both manic
and depressive episodes). Individuals experiencing a
manic episode often have feelings of self-importance,
elation, talkativeness, sociability, and a desire to
embark on goal-oriented activities, coupled with the
less desirable characteristics of irritability, impatience,
impulsiveness, hyperactivity, and a decreased need for
GALE ENCYCLOPEDIA OF MEDICINE

2345

Mania

Love, Susan M., with Karen Lindsey. Dr. Susan Love’s
Breast Book. 3rd ed. Boulder, CO: Perseus Book
Group, 2000.

Marfan syndrome

KEY TERMS
Hypomania—A less severe form of elevated mood
state that is a characteristic of bipolar type II disorder.
Mixed mania—A mental state in which symptoms
of both depression and mania occur simultaneously.

mood-stabilizing agents. The drug is often used to
treat bipolar patients who have not responded well to
lithium therapy. As of early 1998, carbamazepine was
not approved for the treatment of mania by the FDA.


Valproate (divalproex sodium, or Depakote; valproic acid, or Depakene) is an anticonvulsant drug
prescribed alone or in combination with carbamazepine and/or lithium. For patients experiencing ‘‘mixed
mania,’’ or mania with features of depression, valproate is preferred over lithium.

Clozapine (Clozaril) is an atypical antipsychotic
medication used to control manic episodes in patients
who have not responded to typical mood-stabilizing
agents. The drug has also been a useful preventative
treatment in some bipolar patients. Other new anticonvulsants (lamotrigine, gubapentin) are being investigated for treatment of mania and bipolar disorder.

Prognosis
Patients experiencing mania as a result of bipolar
disorder will require long-term care to prevent recurrence; bipolar disorder is a chronic condition that
requires lifelong observation and treatment after diagnosis. Data show that almost 90% of patients who
experience one manic episode will go on to have another.

Prevention
Mania as a result of bipolar disorder can only be
prevented through ongoing pharmacologic treatment.
Patient education in the form of therapy or self-help
groups is crucial for training patients to recognize
signs of mania and to take an active part in their
treatment program. Psychotherapy is an important
adjunctive treatment for patients with bipolar
disorder.
Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington, DC 20005. (888) 357-7924. <http://
www.psych.org>.
2346

National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.
National Depressive and Manic-Depressive Association
(NDMDA). 730 N. Franklin St., Suite 501, Chicago, IL
60610. (800) 826-3632. <http://www.ndmda.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Paula Anne Ford-Martin

Manic depression see Bipolar disorder
Manic episode see Mania
MAO inhibitors see Monoamine oxidase
inhibitors
Marasmus see Protein-energy malnutrition
Marble bones see Osteopetroses
Marburg virus infection see Hemorrhagic
fevers

Marfan syndrome
Definition
Marfan syndrome is an inherited disorder of the
connective tissue that causes abnormalities of the
patient’s eyes, cardiovascular system, and musculoskeletal system. It is named for the French pediatrician,
Antoine Marfan (1858-1942), who first described it in
1896. Marfan syndrome is sometimes called arachnodactyly, which means ‘‘spider-like fingers’’ in Greek,
since one of the characteristic signs of the disease
is disproportionately long fingers and toes. It is estimated that one person in every 3000-5000 has Marfan
syndrome, or about 50,000 people in the United
States. Marfan syndrome is one of the more common
inheritable disorders.

Description
Marfan syndrome affects three major organ systems of the body: the heart and circulatory system, the
bones and muscles, and the eyes. The genetic mutation
responsible for Marfan was discovered in 1991. It affects
the body’s production of fibrillin, which is a protein that
is an important part of connective tissue. Fibrillin is the
primary component of the microfibrils that allow tissues
to stretch repeatedly without weakening. Because the
GALE ENCYCLOPEDIA OF MEDICINE

The most common external signs associated with
Marfan syndrome include excessively long arms and
legs, with the patient’s arm span being greater than his
or her height. The fingers and toes may be long and
slender, with loose joints that can be bent beyond their
normal limits. This unusual flexibility is called hypermobility. The patient’s face may also be long and
narrow, and he or she may have a noticeable curvature
of the spine. It is important to note, however, that
Marfan patients vary widely in the external signs of
their disorder and in their severity; even two patients
from the same family may look quite different. Most
of the external features of Marfan syndrome become
more pronounced as the patient gets older, so that
diagnosis of the disorder is often easier in adults than
in children. In many cases, the patient may have few or
very minor outward signs of the disorder, and the
diagnosis may be missed until the patient develops
vision problems or cardiac symptoms.
Marfan syndrome by itself does not affect a person’s intelligence or ability to learn. There is, however,
some clinical evidence that children with Marfan have a
slightly higher rate of hyperactivity and attention-deficit
disorder (ADD) than the general population. In addition, a child with undiagnosed nearsightedness related
to Marfan may have difficulty seeing the blackboard or
reading printed materials, and thus do poorly in school.

variety of symptoms of very different degrees of severity, even in members of the same family.
Cardiac and circulatory abnormalities
The most important complications of Marfan are
those affecting the heart and major blood vessels;
some are potentially life-threatening. About 90% of
Marfan patients will develop cardiac complications.


Aortic enlargement. This is the most serious potential complication of Marfan syndrome. Because of
the abnormalities of the patient’s fibrillin, the walls
of the aorta (the large blood vessel that carries blood
away from the heart) are weaker than normal and
tend to stretch and bulge out of shape. This stretching increases the likelihood of an aortic dissection,
which is a tear or separation between the layers of
tissue that make up the aorta. An aortic dissection
usually causes severe pain in the abdomen, back, or
chest, depending on the section of the aorta that is
affected. Rupture of the aorta is a medical emergency
requiring immediate surgery and medication.



Aortic regurgitation. A weakened and enlarged
aorta may allow some blood to leak back into the
heart during each heartbeat; this condition is called
aortic regurgitation. Aortic regurgitation occasionally causes shortness of breath during normal activity. In serious cases, it causes the left ventricle of the
heart to enlarge and may eventually lead to heart
failure.



Mitral valve prolapse. Between 75 and 85% of Marfan
patients have loose or ‘‘floppy’’ mitral valves, which
are the valves that separate the chambers of the heart.
When these valves do not cover the opening between
the chambers completely, the condition is called mitral
valve prolapse. Complications of mitral valve prolapse
include heart murmurs and arrhythmias. In rare cases,
mitral valve prolapse can cause sudden death.



Infective endocarditis. Infective endocarditis is an
infection of the endothelium, the tissue that lines
the heart. In patients with Marfan, it is the abnormal
mitral valve that is most likely to become infected.



Other complications. Some patients with Marfan
develop cystic disease of the lungs or recurrent spontaneous pneumothorax, which is a condition in which
air accumulates in the space around the lungs. Many
will also eventually develop emphysema.

Marfan syndrome affects males and females
equally, and appears to be distributed equally among
all races and ethnic groups. The rate of mutation of the
fibrillin gene, however, appears to be related to the age
of the patient’s father; older fathers are more likely to
have new mutations appear in chromosome 15.

Causes and symptoms
Marfan syndrome is caused by a single gene for
fibrillin on chromosome 15, which is inherited in most
cases from an affected parent. Between 15 and 25% of
cases result from spontaneous mutations. Mutations
of the fibrillin gene (FBNI) are unique to each family
affected by Marfan, which makes rapid genetic
diagnosis impossible, given present technology. The
syndrome is an autosomal dominant disorder, which
means that someone who has it has a 50% chance of
passing it on to any offspring.
Another important genetic characteristic of
Marfan syndrome is variable expression. This term
means that the mutated fibrillin gene can produce a
GALE ENCYCLOPEDIA OF MEDICINE

Musculoskeletal abnormalities
Marfan syndrome causes an increase in the length
of the patient’s bones, with decreased support from
the ligaments that hold the bones together. As a result,
2347

Marfan syndrome

patient’s fibrillin is abnormal, his or her connective
tissues are looser than usual, which weakens or damages
the support structures of the entire body.

Marfan syndrome

the patient may develop various deformities of the
skeleton or disorders related to the relative looseness
of the ligaments.

acetabulum becomes deeper than normal during
growth, for reasons that are not yet understood.
Although protrusio acetabulae does not cause problems during childhood and adolescence, it can lead
to a painful form of arthritis in adult life.

Disorders of the spine




Scoliosis. Scoliosis, or curvature of the spine, is a
disorder in which the vertebrae that make up the
spine twist out of line from side to side into an
S-shape or a spiral. It is caused by a combination of
the rapid growth of children with Marfan, and the
looseness of the ligaments that help the spine to keep
its shape.
Kyphosis is an abnormal outward curvature of the
spine at the back, sometimes called hunch back when
it occurs in the upper back. Marfan patients may
develop kyphosis either in the upper (thoracic)
spine or the lower (lumbar) spine.



Spondylolisthesis. Spondylolisthesis is the medical
term for a forward slippage of one vertebra on the
one below it. It produces an ache or stiffness in the
lower back.



Dural ectasia. The dura is the tough, fibrous outermost membrane covering the brain and the spinal
cord. The weak dura in Marfan patients swells or
bulges under the pressure of the spinal fluid. This
swelling is called ectasia. In most cases, dural ectasia
occurs in the lower spine, producing low back
ache, a burning feeling, or numbness or weakness
in the legs.

Disorders of the eyes and face
Although the visual problems that are related
to Marfan syndrome are rarely life-threatening, they
are important in that they may be the patient’s first
indication of the disorder. Eye disorders related to the
syndrome include the following:


Myopia (nearsightedness). Most patients with Marfan
develop nearsightedness, usually in childhood.



Ectopia lentis. Ectopia lentis is the medical term for
dislocation of the lens of the eye. Between 65 and
75% of Marfan patients have dislocated lenses. This
condition is an important indication for diagnosis of
the syndrome because there are relatively few other
disorders that produce it.



Glaucoma. This condition is much more prevalent in
patients with Marfan syndrome than in the general
population.



Cataracts. Patients with Marfan are more likely to
develop cataracts, and to develop them much earlier
in life, sometimes as early as 40 years of age.



Retinal detachment. Patients with Marfan are more
vulnerable to this disorder because of the weakness of
their connective tissues. Untreated retinal detachment
can cause blindness. The danger of retinal detachment
is an important reason for patients to avoid contact
sports or other activities that could cause a blow on
the head or being knocked to the ground.



Other facial problems. Patients with Marfan sometimes develop dental problems related to crowding of
the teeth caused by a high-arched palate and a narrow jaw.

Disorders of the chest and lower body








Pectus excavatum. Pectus excavatum is a malformation of the chest in which the patient’s breastbone, or
sternum, is sunken inward. It can cause difficulties in
breathing, especially if the heart, spine, and lung
have been affected by Marfan. It also usually causes
concerns about appearance.
Pectus carinatum. In other patients with Marfan the
sternum is pushed outward and narrowed. Although
pectus carinatum does not cause breathing difficulties, it can cause embarassment about appearance. A
few patients with Marfan may have a pectus excavatum on one side of their chest and a pectus carinatum
on the other.
Foot disorders. Patients with Marfan are more likely
to develop pes planus (flat feet) or so-called ‘‘claw’’
or ‘‘hammer’’ toes than people in the general population. They are also more likely to suffer from chronic
pain in their feet.
Protrusio acetabulae. The acetabulum is the socket
of the hip joint. In patient’s with Marfan, the

2348

Other disorders


Striae. Striae are stretch marks in the skin caused by
rapid weight gain or growth; they frequently occur in
pregnant women, for example. Marfan patients often
develop striae over the shoulders, hips, and lower
back at an early age because of rapid bone growth.
Although the patient may be self-conscious about the
striae, they are not a danger to health.



Obstructive sleep apnea. Obstructive sleep apnea
refers to partial obstruction of the airway during
sleep, causing irregular breathing and sometimes
snoring. In patients with Marfan, obstructive sleep
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Presently, there is no objective diagnostic test for
Marfan syndrome, in part because the disorder does
not produce any measurable biochemical changes in
the patient’s blood or body fluids, or cellular changes
that could be detected from a tissue sample. Although
researchers in molecular biology are currently investigating the FBNI gene through a process called
mutational analysis, it is presently not useful as a
diagnostic test because there is evidence that there
can be mutations in the fibrillin gene that do not
produce Marfan. Similarly, there is no reliable
prenatal test, although some physicians have used
ultrasound to try to determine the length of fetal
limbs in at-risk pregnancies.
The diagnosis is made by taking a family history
and a thorough examination of the patient’s eyes,
heart, and bone structure. The examination should
include an echocardiogram taken by a cardiologist, a
slit-lamp eye examination by an ophthalmologist,
and a work-up of the patient’s spinal column by an
orthopedic specialist. In terms of the cardiac examination, a standard electrocardiogram (EKG) is not
sufficient for diagnosis; only the echocardiogram
can detect possible enlargement of the aorta. The
importance of the slit-lamp examination is that it
allows the doctor to detect a dislocated lens, which is
a significant indication of the syndrome.
The symptoms of Marfan syndrome in some
patients resemble the symptoms of homocystinuria,
which is an inherited disorder marked by extremely
high levels of homocystine in the patient’s blood
and urine. This possibility can be excluded by a
urine test.
In other cases, the diagnosis remains uncertain
because of the mildness of the patient’s symptoms,
the absence of a family history of the syndrome, and
other variables. These borderline conditions are sometimes referred to as marfanoid syndromes.

Treatment
The treatment and management of Marfan is tailored to the specific symptoms of each patient. Some
patients find that the syndrome has little impact on
their overall lifestyle; others have found their lives
centered on the disorder.
GALE ENCYCLOPEDIA OF MEDICINE

Cardiovascular system
After a person has been diagnosed with Marfan,
he or she should be monitored with an echocardiogram every six months until it is clear that the aorta is
not growing larger. After that, the patient should have
an echocardiogram once a year. If the echocardiogram
does not allow the physician to visualize all portions of
the aorta, CT (computed tomography) or MRI (magnetic resonance imaging) may be used. In cases involving a possible aortic dissection, the patient may be
given a TEE (transesophageal echocardiogram).
Medications. A Marfan patient may be given
drugs called beta-blockers to slow down the rate of
aortic enlargement and decrease the risk of dissection
by lowering the blood pressure and decreasing the
forcefulness of the heartbeat. The most commonly
used beta-blockers in Marfan patients are propranolol
(Inderal) and atenolol (Tenormin). Patients who are
allergic to beta-blockers may be given a calcium
blocker such as verapamil.
Because Marfan patients are at increased risk for
infective endocarditis, they must take a prophylactic
dose of an antibiotic before having dental work or
minor surgery, as these procedures may allow bacteria
to enter the bloodstream. Penicillin and amoxicillin
are the antibiotics most often used.
Surgical treatment. Surgery may be necessary if
the width of the patient’s aorta increases rapidly or
reaches a critical size (about 2 inches). As of 2000, the
most common surgical treatment involves replacing
the patient’s aortic valve and several inches of the
aorta itself with a composite graft, which is a prosthetic heart valve sewn into one end of a Dacron tube.
This surgery has been performed widely since about
1985; most patients who have had a composite graft
have not needed additional surgery.
Patients who have had a valve replaced must take
an anticoagulant medication, usually warfarin
(Coumadin), in order to minimize the possibility of a
clot forming on the prosthetic valve.
Musculoskeletal system
Children diagnosed with Marfan should be
checked for scoliosis by their pediatricians at each
annual physical examination. The doctor simply asks
the child to bend forward while the back is examined
for changes in the curvature. In addition, the child’s
spine should be x rayed in order to measure the extent
of scoliosis or kyphosis. The curve is measured in
degrees by the angle between the vertebrae as seen on
the x ray. Curves of 208 or less are not likely to become
2349

Marfan syndrome

apnea is caused by the unusual flexibility of the
tissues lining the patient’s airway. This disturbed
breathing pattern increases the risk of aortic
dissection.

Marfan syndrome

worse. Curves between 20 and 40 degrees are likely to
increase in children or adolescents. Curves of 40
degrees or more are highly likely to worsen, even in
an adult, because the spine is so badly imbalanced that
the force of gravity will increase the curvature.
Scoliosis between 20 and 40 degrees in children is
usually treated with a back brace. The child must wear
this appliance about 23 hours a day until growth is
complete. If the spinal curvature increases to 40 or 50
degrees, the patient may require surgery in order to
prevent lung problems, back pain, and further deformity. Surgical treatment of scoliosis involves straightening the spine with metal rods and fusing the
vertebrae in the straightened position.
Spondylolisthesis is treated with a brace in mild
cases. If the slippage is more than 30 degree, the
slipped vertebra may require surgical realignment.
Dural ectasia can be distinguished from other
causes of back pain on an MRI. Mild cases are usually
not treated. Medication or spinal shunting to remove
some of the spinal fluid are used to treat severe cases.
Pectus excavatum and pectus carinatum can be
treated by surgery. In pectus excavatum, the deformed
breastbone and ribs are raised and straightened by a
metal bar. After four to six months, the bar is removed
in an outpatient procedure.
Protrusio acetabulae may require surgery in adult
life to provide the patient with an artificial hip joint, if
the arthritic pains are severe.
Pain in the feet or limbs is usually treated with a
mild analgesic such as acetaminophen. Patients with
Marfan should consider wearing shoes with low heels,
special cushions, or orthotic inserts. Foot surgery is
rarely necessary.
Visual and dental concerns
Patients with Marfan should have a thorough eye
examination, including a slit-lamp examination, to
test for dislocation of the lens as well as nearsightedness. Dislocation can be treated by a combination of
special glasses and daily use of one percent atropine
sulfate ophthalmic drops, or by surgery.
Because patients with Marfan are at increased risk
of glaucoma, they should have the fluid pressure inside
the eye measured every year as part of an eye examination. Glaucoma can be treated with medications or
with surgery.
Cataracts are treated with increasing success by
implant surgery. It is important, however, to seek
treatment at medical centers with eye surgeons
2350

familiar with the possible complications of cataract
surgery in patients with Marfan syndrome.
All persons with Marfan should be taught to
recognize the signs of retinal detachment (sudden blurring of vision in one eye becoming progressively worse
without pain or redness) and to seek professional help
immediately.
Children with Marfan should be evaluated by
their dentist at each checkup for crowding of the
teeth and possible misalignment, and referred to an
orthodontist if necessary.
Athletic activities and occupational choice.
People with Marfan should avoid sports or occupations that require heavy weight lifting, rough physical
contact, or rapid changes in atmospheric pressure
(e.g., scuba diving). Weight lifting increases blood
pressure, which in turn may enlarge the aorta. Rough
physical contact may cause retinal detachment.
Sudden changes in air pressure may produce pneumothorax. Regular noncompetitive physical exercise,
however, is beneficial for Marfan patients. Good
choices include brisk walking, shooting baskets, and
slow-paced tennis.
Social and lifestyle issues
Smoking. Smoking is particularly harmful for
Marfan patients because it increases their risk of
emphysema.
Pregnancy. Until very recently, women with
Marfan were advised not to become pregnant because
of the risk of aortic enlargement or dissection. The
development of beta-blockers and echocardiograms,
however, allows doctors now to monitor patients
throughout pregnancy. It is recommended that patients
have an echocardiogram during each of the three trimesters of pregnancy. Normal, vaginal delivery is not
necessarily more stressful than a Caesarian section, but
patients in prolonged labor may be given a Caesarian to
reduce strain on the heart. A pregnant woman with
Marfan should also receive genetic counseling regarding
the 50% risk of having a child with the syndrome.
Appearance and Social Concerns. Children and
adolescents with Marfan may benefit from supportive
counseling regarding appearance, particularly if their
symptoms are severe and causing them to withdraw
from social activities. In addition, families may wish to
seek counseling regarding the effects of the syndrome
on relationships within the family. Many people
respond with guilt, fear, or blame when a genetic disorder is diagnosed in the family, or they may overprotect the affected member. Support groups are often
good sources of information about Marfan; they can
GALE ENCYCLOPEDIA OF MEDICINE

Arachnodactyly—A condition characterized by
abnormally long and slender fingers and toes.
Ectopia lentis—Dislocation of the lens of the eye. It
is one of the most important single indicators in
diagnosing Marfan syndrome.
Fibrillin—A protein that is an important part of the
structure of the body’s connective tissue. In
Marfan’s syndrome, the gene responsible for fibrillin has mutated, causing the body to produce a
defective protein.
Hypermobility—Unusual flexibility of the joints,
allowing them to be bent or moved beyond their
normal range of motion.
Kyphosis—An abnormal outward curvature of the
spine, with a hump at the upper back.
Pectus carinatum—An abnormality of the chest in
which the sternum (breastbone) is pushed outward.
It is sometimes called ‘‘pigeon breast.’’
Pectus excavatum—An abnormality of the chest in
which the sternum (breastbone) sinks inward;
sometimes called ‘‘funnel chest.’’
Scoliosis—An abnormal, side-to-side curvature of
the spine.

offer helpful suggestions about living with it as well as
emotional support.

Prognosis
The prognosis for patient’s with Marfan has
improved markedly in recent years. As of 1995, the
life expectancy of people with the syndrome has
increased to 72 years, up from 48 years in 1972. This
dramatic improvement is attributed to new surgical
techniques, improved diagnosis, and new techniques
of medical treatment.
The most important single factor in improving the
patient’s prognosis is early diagnosis. The earlier that
a patient can benefit from the new techniques and
lifestyle modifications, the more likely he or she is to
have a longer life expectancy.
Resources
BOOKS

Beers, Mark H., and Robert Berkow, editors. Pediatrics.
Whitehouse Station, NJ: Merck Research
Laboratories, 1999.
GALE ENCYCLOPEDIA OF MEDICINE

Pyeritz, Reed E., and Cheryll Gasner. The Marfan
Syndrome. New York: National Marfan Syndrome,
1999.

Rebecca J. Frey, PhD

Marie-Strümpell disease see Ankylosing
spondylitis

Marijuana
Definition
Marijuana (marihuana) Cannabis sativa L., also
known as Indian hemp, is a member of the
Cannabaceae or hemp family, thought to have originated in the mountainous districts of India, north of
the Himalayan mountains.

Description
The herb was referred to as ‘‘hempe’’ in A.D. 1000
and listed in a dictionary under that English name.
Supporters of the notorious Pancho Villa first used the
name marijuana in 1895 in Sonora, Mexico. They
called the mood-altering herb they smoked marijuana.
The term hashish, is derived from the name for the
Saracen soldiers, called hashashins, who ingested the
highly potent cannabis resin before being sent out to
assassinate enemies.
Two related species of cannabis are C. ruderalis,
and C. indica, a variety known as Indian hemp. Indian
hemp grows to a height of about 4 ft (1.2 m) and the
seed coats have a marbled appearance.
The species C. sativa L. has many variations,
depending on the soil, temperature, and light conditions, and the origin of the parent seed. These factors
also affect the relative amounts of THC (tetra-hydrocannabinol) and cannabidiol, the chemicals present in
varying amounts in cannabis that determine if the
plant is primarily a fiber type or an intoxicant.
Generally the species grown at higher elevations and
in hotter climates exudes more of the resin and is more
medicinally potent.
Marijuana is a somewhat weedy plant and may
grow as high as 18 ft (5.4 m). The hairy leaves are
arranged opposite one another on the erect and
branching stem. Leaves are palmate and compound,
deeply divided into five to seven narrow, toothed and
pointed leaflets. Male and female flowers are small
and greenish in color and grow on separate plants.
2351

Marijuana

KEY TERMS

Marijuana

Male flowers grow in the leaf axils in elongated clusters. The female flowers grow in spike-like clusters.
The resinous blossoms have five sepals and five petals.
The male and female blossoms can be distinguished at
maturity. The male plant matures first, shedding its
pollen and dying after flowering. Female plants die
after dropping the mature seeds. Marijuana produces
an abundance of quickly germinating seeds. This
hardy annual is wind pollinated and has escaped
from cultivation to grow wild along roadsides, trails,
stream banks, and in wayside places throughout the
world. The plant matures within three to five months
after the seed has been sown.
History
Marijuana has been cultivated for thousands of
years. Cannabis was first described for its therapeutic
use in the first known Chinese pharmacopoeia, the
Pen Ts’ao. (A pharmacopoeia is a book containing a
list of medicinal drugs, and their descriptions of preparation and use.) Cannabis was called a ‘‘superior’’
herb by the Emperor Shen-Nung (2737-2697 B.C.),
who is believed to have authored the work. Cannabis
was recommended as a treatment for numerous common ailments. Around that same period in Egypt,
cannabis was used as a treatment for sore eyes. The
herb was used in India in cultural and religious ceremonies, and recorded in Sanskrit scriptural texts
around 1,400 B.C. Cannabis was considered a holy
herb and was characterized as the ‘‘soother of grief,’’
‘‘the sky flyer,’’ and ‘‘the poor man’s heaven.’’
Centuries later, around 700 B.C., the Assyrian people
used the herb they called Qunnabu, for incense. The
ancient Greeks used cannabis as a remedy to treat
inflammation, earache, and edema (swelling of a
body part due to collection of fluids). Shortly after
500 B.C. the historian and geographer Herodotus
recorded that the peoples known as Scythians used
cannabis to produce fine linens. They called the herb
kannabis and inhaled the ‘‘intoxicating vapor’’ that
resulted when it was burned. By the year 100 B.C. the
Chinese were using cannabis to make paper.
Cannabis use and cultivation migrated with the
movement of various traders and travelers, and
knowledge of the herb’s value spread throughout the
Middle East, Eastern Europe, and Africa. Around
100, Dioscorides, a surgeon in the Roman Legions
under the Emperor Nero, named the herb Cannabis
sativa and recorded numerous medicinal uses. In the
second century, the Chinese physician Hoa-Tho, used
cannabis in surgical procedures, relying on its analgesic properties. In ancient India, around 600, Sanskrit
writers recorded a recipe for ‘‘pills of gaiety,’’ a
2352

combination of hemp and sugar. By 1150, Moslems
were using cannabis fiber in Europe’s first paper
production. This use of cannabis as a durable and
renewable source of paper fiber continued for the
next 750 years.
By the 1300s, government and religious authorities,
concerned about the psychoactive effects on citizens
consuming the herb, were placing harsh restrictions
on its use. The Emir Soudon Sheikhouni of Joneima
outlawed cannabis use among the poor. He destroyed
the crops and ordered that offenders’ teeth be pulled
out. In 1484, Pope Innocent VIII outlawed the use of
hashish, a concentrated form of cannabis. Cannabis
cultivation continued, however, because of its economic value. A little more than a century later, the
English Queen Elizabeth I issued a decree commanding
that landowners holding sixty acres or more must grow
hemp or pay a fine. Commerce in hemp, which was
primarily valued for the strength and versatility of its
fibers, was profitable and thriving. Hemp ropes and
sails were crossing the sea to North America with the
explorers. By 1621, the British were growing cannabis
in Virginia where cultivation of hemp was mandatory.
In 1776, the Declaration of Independence was drafted
on hemp paper. Both President George Washington
and President Thomas Jefferson were advocates of
hemp as a valuable cash crop. Jefferson urged farmers
to grow the crop in lieu of tobacco. By the 1850s, hemp
had become the third largest agricultural crop grown in
North America. The U. S. Census of that year recorded
8,327 hemp plantations, each with 2,000 or more acres
in cultivation. But the invention of the cotton gin was
already bringing many changes, and cotton was becoming a prime and profitable textile fiber. More change
came with the introduction of the sulfite and chlorine
processes used to turn trees into paper. Restrictions
on the personal use of cannabis as a mood-altering,
psychoactive herb, were soon to come.

Controversy
The 1856 edition of the Encyclopedia Britannica, in
its lengthy entry on hemp, noted that the herb ‘‘produces inebriation and delirium of decidedly hilarious
character, inducing violent laughter, jumping and dancing.’’ This inebriating effect of marijuana use has fueled
the controversy and led to restrictions that have surrounded marijuana use throughout history in many
cultures and regions of the world. Cannabis use has
been criminalized in some parts of the United States
since 1915. Utah was the first state to criminalize it,
then California and Texas. By 1923, Louisiana,
Nevada, Oregon, and Washington had legal restrictions
on the herb. New York prohibited cannabis use in 1927.
GALE ENCYCLOPEDIA OF MEDICINE

In 1937, the federal government passed the
Marihuana Tax Act, prohibiting the cultivation and
farming of marijuana. This bill was introduced to
Congress by then Secretary of the Treasury Andrew
Mellon, who was also a banker for the DuPont
Corporation. That same year, the DuPont Chemical
Company filed a patent for nylon, plastics, and a new
bleaching process for paper. The 1937 Marijuana
Transfer Tax Bill prohibited industrial and medical
use of marijuana and classified the flowering tops as
narcotic, and restrictions on the cultivation and use of
cannabis continued. Marijuana was categorized as an
illegal narcotic, in the company of LSD and heroin,
cocaine, and morphine. Illegal use continued. The FBI
publication, Uniform Crime Reports for The United
States, 1966 reported that 641,642 Americans were
arrested for marijuana offenses that year, with as
many as 85% of these arrests for simple possession,
rather than cultivation or commerce.
In a reversal of the state-by-state progression of
criminalizing marijuana that led to the 1937
Marijuana Transfer Tax Bill, there is a movement
underway, state by state, to endorse the legalized use
of medical marijuana. By 1992, 35 states in the U. S.
had endorsed referenda for medical marijuana. A
growing body of scientific research and many thousands of years of folk use support the importance of
medical marijuana in treatment of a variety of illnesses, and the economic value of hemp in the textile,
paper, and cordage industries has a long history.
The controversy and misinformation persists
around this relatively safe and non-toxic herb. The
World Health Organization, in a 1998 study, stated
that the risks from cannabis use were unlikely to seriously compare to the public health risks of the legal
drugs, alcohol and tobacco. And despite thousands of
years of human consumption, not one death has been
directly attributed to cannabis use. According to
Lester Grinspoon, MD, and James B. Bakalar, JD,
in a 1995 Journal of the American Medical Association
article, ‘‘Marihuana is also far less addictive and far
less subject to abuse than many drugs now used as
muscle relaxants, hypnotics, and analgesics. The chief
legitimate concern is the effect of smoking on the
lungs. Cannabis smoke carries even more tars and
other particulate matter than tobacco smoke. But the
amount smoked is much less, especially in medical use,
and once marihuana is an openly recognized medicine,
solutions may be found.’’
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
The whole cannabis plant, including buds, leaves,
seeds, and root, have all been utilized throughout the
long history of this controversial herb. Despite persistent
legal restrictions and severe criminal penalties for illicit
use, marijuana continues to be widely used in the United
States, and throughout the world, both for its moodaltering properties and its proven medicinal applications. The conflicting opinions on the safety and
effectiveness of cannabis in a climate of prohibition
make any discussion of its beneficial uses politically
charged. Marijuana has analgesic, antiemetic, antiinflammatory, sedative, anticonvulsive, and laxative
actions. Clinical studies have demonstrated its effectiveness in relieving nausea and vomiting following chemotherapy treatments for cancer. The herb has also
been shown to reduce intra-ocular pressure in the eye
by as much as 45%, a beneficial action in the treatment
for glaucoma. Cannabis has proven anticonvulsive
action, and may be helpful in treating epilepsy. Other
research has documented an in-vitro tumor inhibiting
effect of THC. Marijuana also increases appetite and
reduces nausea and has been used with AIDS patients to
counter weight loss and ‘‘wasting’’ that may result
from the disease. Several chemical constituents of cannabis displayed antimicrobial action and antibacterial
effects in research studies. The components CBC and d9-tetrahydrocannabinol have been shown to destroy and
inhibit the growth of streptococci and staphylococci
bacteria.
Cannabis contains chemical compounds known
as cannabinoids. Different cannabinoids seem to
exert different effects on the body after ingestion.
Scientific research indicates that these substances
have potential therapeutic value for pain relief, control
of nausea and vomiting, and appetite stimulation. The
primary active agent identified to date is 9-tetrahydrocannabinol, known as THC. This chemical may constitute as much as 12% of the active chemicals in
the herb, and is said to be responsible for as much as
70–100% of the euphoric action, or ‘‘high,’’ experienced when ingesting the herb. The predominance of
this mental lightness or ‘‘euphoria’’ depends on the
balance of other active ingredients and the freshness
of the herb. THC degrades into a component known
as cannabinol, or CBN. This relatively inactive chemical predominates in marijuana that has been stored
too long prior to use. Another chemical component,
cannabidiol, known as CBD, has a sedative and mildly
analgesic effect, and contributes to a somatic heaviness sometimes experienced by marijuana users.
for

Before prohibition, cannabis was recommended
treatment of gonorrhea, angina pectoris
2353

Marijuana

Despite the restrictions, cannabis use was woven into
the cultural and social fabric in some communities, and
widespread use persisted, particularly among the
Mexican, Asian, and African American populations.

Marijuana

(constricting pain in the chest due to insufficient blood
to the heart), and choking fits. It was also used for
insomnia, neuralgia, rheumatism, gastrointestinal disorders, cholera, tetanus, epilepsy, strychnine poisoning,
bronchitis, whooping cough, and asthma. Other phytotherapeutic (plant-based therapeutic) uses include
treatment of ulcers, cancer, emphysema, migraine,
Lou Gehrig’s disease, HIV infection, and multiple
sclerosis.
The United States federal government policy
prohibits physicians from prescribing marijuana,
even for seriously ill patients because of possible
adverse effects, and the disputed belief that cannabis
is dangerously addictive. U. S. Attorney General Janet
Reno warned that physicians in any state who
prescribed marijuana could lose the privilege of writing prescriptions, be excluded from Medicare and
Medicaid reimbursement, and even be prosecuted for
a federal crime, according to a 1997 editorial in the
New England Journal of Medicine.

Preparations
Cannabis extracts, prepared for medicinal application, are prohibited in the United States. Marijuana is
ingested by smoking, which quickly delivers the active
ingredients to the blood system. The dried herb can also
be prepared for eating in cookies or other baked goods.
The essential oil consists of beta caryophyllenes,
humules, caryophyllene oxide, alpha-pinenes, betapinenes, limonene, myrcene, and betaocimene. The oil
expressed from the seeds is used for massage and in
making salves used to relieve muscle strain.

Precautions
Marijauna is considered a Class I narcotic and its
use has been restricted by federal law since 1937.
Penalties include fines and imprisonment. The
National Commission on Marihuana and Drug
Abuse concluded in 1972 that ‘‘A careful search of
the literature and testimony of the nation’s health
officials has not revealed a single human fatality in
the United States proven to have resulted solely from
ingestion of marihuana.’’
Research has shown that cannabis acts to increase
heart frequency by as much as 40 beats per minute. A
study reported by The American Heart Association in
February 2000, concluded that smoking marijuana
can precipitate a heart attack in persons with preexisting heart conditions. One hour after smoking
marijuana, the likelihood of having a heart attack is
four and one-half times greater than if the person had
not smoked, according to the research.
2354

KEY TERMS
Antiemetic—A drug or herbal preparation given to
relieve nausea and vomiting. Marijuana has antiemetic properties.
Cannabinoids—The chemical compounds that are
the active principles in marijuana.
Euphoria—An intense feeling of elation or wellbeing. Many marijuana users experience temporary euphoria.

An additional health concern is the effect that
marijuana smoking has on the lungs. Cannabis
smoke carries more tars and other particulate matter
than tobacco smoke.
Although marijuana is less likely than some other
drugs to lead to dependence, heavy users may suffer a
withdrawal syndrome characterized by anxiety, irritability, chills, and muscle cramps if they stop usage
abruptly.
More seriously, marijuana has been linked to
the onset or worsening of certain psychiatric conditions, including panic disorder, schizophrenia, and
depersonalization disorder. Persons diagnosed with
or at risk for these conditions should not use
marijuana.

Side effects
The PDR For Herbal Medicine reports, ‘‘No health
hazards or side effects are known in conjunction with
the proper administration of designated therapeutic
dosages.’’ Smoking the herb, however, ‘‘ . . . leads
almost at once to euphoric states (pronounced gaiety,
laughing fits),’’ according to the PDR, while ‘‘long term
usage leads to a clear increase in tolerance for most of
the pharmacological effects.’’ The ability to safely operate automobiles and machinery can be impaired for up
to eight hours after ingesting the herb. Chronic abuse
results in ‘‘laryngitis, bronchitis, apathy, psychic
decline and disturbances of genital functions,’’ according to the PDR.
Some people may be hypersensitive to marijuana.
They may be allergic or hypersensitive to the plant.
Chronic sinus fungal infections have been linked to
chronic marijuana smoking.
A team of German researchers reported in early
2004 that marijuana appears to speed up the
GALE ENCYCLOPEDIA OF MEDICINE

Interactions
Marijauna use may mask the perceived effects of
alcohol and cocaine when the drugs are consumed
together. Marijuana is said to exert a synergistic effect
with other medicinal agents. When used with nitrous
oxide it may enhance the effect.

Deerman, Dixie, RN. The Best Herb You’re Not Using That
Could Add Years to Your Life! North Carolina:
Community of Compassion, 2000.
Goddard, Ian Williams. Proven: Cannabis Is Safe Medicine.
<http://sers.erols.com/igoddard/hempsafe.htm>.
Lewin, Louis. Phantastica, Hallucinating Substances, Indian
Hemp: Cannabis Indica. <http://users.lycaeum.org/
sputnik/Ludlow/Texts/phantastica.html>.
Taima in Japan. Drug War Facts: Marijuana.
<http://taima.org/drugfacts/mj.htm>.

Clare Hanrahan
Rebecca J. Frey, PhD

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Cannabis (Marijuana) Dependence.’’ Section 15,
Chapter 195. In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Amtmann, D., P. Weydt, K. L. Johnson, et al. ‘‘Survey of
Cannabis Use in Patients with Amyotrophic Lateral
Sclerosis.’’ American Journal of Hospice and Palliative
Care 21 (March-April 2004): 95–104.
Arsenault, L., M. Cannon, J. Witton, and R. M. Murray.
‘‘Causal Association between Cannabis and Psychosis:
Examination of the Evidence.’’ British Journal of
Psychiatry 184 (February 2004): 110–117.
Dannon, P. N., K. Lowengrub, R. Amiaz, et al. ‘‘Comorbid
Cannabis Use and Panic Disorder: Short Term and
Long Term Follow-Up Study.’’ Human
Psychopharmacology 19 (March 2004): 97–101.
Haney, M., C. L. Hart, S. K. Vosburg, et al. ‘‘Marijuana
Withdrawal in Humans: Effects of Oral THC or
Divalproex.’’ Neuropsychopharmacology 29 (January
2004): 158–170.
Hart, S., O. O. Fischer, and A. Ullrich. ‘‘Cannabinoids
Induce Cancer Cell Proliferation Via Tumor Necrosis
Factor Alpha-Converting Enzyme (TACE/ADAM17)Mediated Transactivation of the Epidermal Growth
Factor Receptor.’’ Cancer Research 64 (March 15,
2004): 1943–1950.
Simeon, D. ‘‘Depersonalisation Disorder: A Contemporary
Overview.’’ CNS Drugs 18 (2004): 343–354.
OTHER

Campaign to Legalise Cannabis International Association.
Cannabis Campaigner’s Guide, Up-to-Date Chronology
of Cannabis Hemp. <http://www.paston.co.uk/users/
webbooks/chronol.html>.
Center for Cardiovascular Education, Inc. Smoking
Marijuana Increases Heart Attack Risk. Heart
Information Network. June 14, 2000. <http://
www.heartinfo.org/news2000/
marijuana061400.htm>.
GALE ENCYCLOPEDIA OF MEDICINE

Marriage counseling
Definition
Marriage counseling is a type of psychotherapy
for a married couple or established partners that tries
to resolve problems in the relationship. Typically, two
people attend counseling sessions together to discuss
specific issues.

Purpose
Marriage counseling is based on research that
shows that individuals and their problems are best
handled within the context of their relationships.
Marriage counselors are trained in psychotherapy
and family systems, and focus on understanding their
clients’ symptoms and the way their interactions contribute to problems in the relationship.

Description
Marriage counseling is usually a short-term therapy that may take only a few sessions to work out
problems in the relationship. Typically, marriage
counselors ask questions about the couple’s roles,
patterns, rules, goals, and beliefs. Therapy often
begins as the couple analyzes the good and bad aspects
of the relationship. The marriage counselor then
works with the couple to help them understand that,
in most cases, both partners are contributing to problems in the relationship. When this is understood,
the two can then learn to change how they interact
with each other to solve problems. The partners may
be encouraged to draw up a contract in which each
partner describes the behavior he or she will be trying
to maintain.
2355

Marriage counseling

progression of cancer. If this finding is replicated by
other researchers, it would limit the usefulness of marijuana in treating pain and depression in cancer
patients.

Marshall-Marchetti-Krantz procedure

Marriage is not a requirement for two people to
get help from a marriage counselor. Anyone person
wishing to improve his or her relationships can get
help with behavioral problems, relationship issues, or
with mental or emotional disorders. Marriage counselors also offer treatment for couples before they get
married to help them understand potential problem
areas. A third type of marriage counseling involves
postmarital therapy, in which divorcing couples who
share children seek help in working out their differences. Couples in the midst of a divorce find that
marriage therapy during separation can help them
find a common ground as they negotiate interpersonal
issues and child custody.
Choosing a therapist
A marriage counselor is trained to use different
types of therapy in work with individuals, couples, and
groups. American Association of Marriage and
Family Therapy (AAMFT) training includes supervision by experienced therapists, a minimum of a master’s degree (including specific training in marriage
and family therapy), and specific graduate training in
marriage and family therapy.
When looking for a marriage counselor, a couple
should find out the counselor’s training and educational background, professional associations, such
as AAMFT, and state licensure, and whether the
person has experience in treating particular kinds of
problem. Also, questions should be asked concerning
fees, insurance coverage, the average length of therapy, and so on.

Definition
The Marshall-Marchetti-Krantz procedure surgically reinforces the bladder neck in order to prevent
unintentional urine loss.

Purpose
The Marshall-Marchetti-Krantz procedure is
performed to correct stress incontinence in women,
a common result of childbirth and/or menopause.
Incontinence also occurs when an individual involuntarily loses urine after pressure is placed on the abdomen (like during exercise, sexual activity, sneezing,
coughing, laughing, or hugging).

Precautions
In some women, stress incontinence may be controlled through nonsurgical means, such as:


Kegel exercises (exercises that tighten pelvic muscles)



Biofeedback (monitors temperature and muscle contractions in the vagina to help incontinent patients
control their pelvic muscles)



Bladder training (behavioral modification program
used to treat stress incontinence)



Medication



Inserted incontinence devices.

Each patient should undergo a full diagnostic
workup to determine the best course of treatment.

Normal results
Marriage counseling helps couples learn to deal
more effectively with problems, and can help prevent
small problems from becoming serious. Research
shows that marriage counseling, when effective,
tends to improve a person’s physical as well as mental
health, in addition to improving the relationship.
Resources
ORGANIZATIONS

American Association for Marriage and Family Therapy.
1133 15th St., NW Suite 300, Washington, DC 200052710. (202) 452-0109. <http://www.aamft.org>.
American Psychological Association (APA). 750 First
St. NE, Washington, DC 20002-4242. (202) 336-5700.
<http://www.apa.org>.

Carol A. Turkington
2356

Marshall-Marchetti-Krantz
procedure

Description
The Marshall-Marchetti-Krantz procedure, also
known as retropubic suspension or bladder neck suspension surgery, is performed by a surgeon in a hospital setting. The patient is placed under general
anesthesia, and a long, thin, flexible tube (catheter) is
inserted into the bladder through the narrow tube
(urethra) that drains the body’s urine. An incision is
made across the abdomen, and the bladder is exposed.
The bladder is separated from surrounding tissues.
Stitches (sutures) are placed in these tissues near the
bladder neck and urethra. The urethra is then lifted,
and the sutures are attached to the pubic bone itself, or
to tissue (fascia) behind the pubic bone. The sutures
support the bladder neck, helping the patient gain
control over urine flow.
GALE ENCYCLOPEDIA OF MEDICINE

Biofeedback—Biofeedback training monitors temperature and muscle contractions in the vagina to
help incontinent patients control their pelvic muscles.
Bladder training—A behavioral modification program used to treat stress incontinence. Bladder
training involves putting the patient on a toilet
schedule, and gradually increasing the time interval between urination.
Catheter—A long, thin, flexible tube. A catheter is
used to drain the bladder of urine during a
Marshall-Marchetti-Krantz procedure.
Kegel exercises—Exercises that tighten the pelvic
floor muscles. Kegel exercises can assist some
women in controlling their stress incontinence.
Urethra—The narrow tube, leading from the bladder that drains the body’s urine.

risks of infection, internal bleeding, and hemorrhage.
There is also a possibility of permanent damage to the
bladder or urethra. The urethra may become scarred,
causing a permanent narrowing, or stricture.

Normal results
Approximately 85% of women who undergo the
Marshall-Marchetti-Krantz procedure are cured of
their stress incontinence.
Resources
ORGANIZATIONS

American Foundation for Urologic Disease. 1128 North
Charles St., Baltimore, MD 21201. (800) 242-2383.
<http://www.afud.org>.
National Association for Continence. P.O. Box 8310,
Spartanburg, SC 29305-8310. (800) 252-3337. <http://
www.nafc.org>.

Paula Anne Ford-Martin

Preparation
A complete evaluation to determine the cause of
incontinence is critical to proper treatment. A thorough medical history and general physical examination
should be performed on candidates for the MarshallMarchetti-Krantz procedure. Diagnostic testing may
include x rays, ultrasound, urine tests, and examination of the pelvis. It may also include a series of urodynamic testing exams that measure bladder pressure
and capacity, and urinary flow.
Patients undergoing a Marshall-Marchetti-Krantz
procedure must not eat or drink for eight hours prior
to the surgery.

Aftercare
Recovery from a Marshall-Marchetti-Krantz
procedure requires two to six days of hospitalization.
The catheter will be removed from the patient’s bladder once normal bladder function resumes. Patients
are advised to refrain from heavy lifting for four to
six weeks after the procedure.
Patients should contact their physician immediately
if they experience fever, dizziness, or extreme nausea,
or if their incision site becomes swollen, red, or hard.

Risks
The Marshall-Marchetti-Krantz procedure is an
invasive surgical procedure and, as such, it carries
GALE ENCYCLOPEDIA OF MEDICINE

Massage therapy
Definition
Massage therapy is the scientific manipulation of
the soft tissues of the body for the purpose of normalizing those tissues and consists of manual techniques
that include applying fixed or movable pressure, holding, and/or causing movement of or to the body.

Purpose
Generally, massage is known to affect the circulation of blood and the flow of blood and lymph, reduce
muscular tension or flaccidity, affect the nervous
system through stimulation or sedation, and enhance
tissue healing. These effects provide a number of
benefits:


reduction of muscle tension and stiffness



relief of muscle spasms



greater flexibility and range of motion



increase of the ease and efficiency of movement



relief of stress and aide of relaxation



promotion of deeper and easier breathing



improvement of the circulation of blood and movement of lymph
2357

Massage therapy

KEY TERMS

Massage therapy



relief of tension-related conditions, such as headaches and eyestrain



promotion of faster healing of soft tissue injuries,
such as pulled muscles and sprained ligaments, and
reduction in pain and swelling related to such injuries



reduction in the formation of excessive scar tissue
following soft tissue injuries



enhancement in the health and nourishment of skin



improvement in posture through changing tension
patterns that affect posture



reduction in stress and an excellent stress management tool



creation of a feeling of well-being



reduction in levels of anxiety



increase in awareness of the mind-body connection



promotion of a relaxed state of mental awareness

Massage therapy also has a number of documented clinical benefits. For example, massage can reduce
anxiety, improve pulmonary function in young asthma
patients, reduce psycho-emotional distress in persons
suffering from chronic inflammatory bowel disease,
increase weight and improve motor development in
premature infants, and may enhance immune system
functioning. Some medical conditions that massage
therapy can help are: allergies, anxiety and stress,
arthritis, asthma and bronchitis, carpal tunnel syndrome and other repetitive motion injuries, chronic
and temporary pain, circulatory problems, depression,
digestive disorders, tension headache, insomnia, myofascial pain, sports injuries, and temporomandibular
joint dysfunction.

Description
Origins
Massage therapy is one of the oldest health care
practices known to history. References to massage are
found in Chinese medical texts more than 4,000 years
old. Massage has been advocated in Western health
care practices at least since the time of Hippocrates,
the ‘‘Father of Medicine.’’ In the fourth century B.C.
Hippocrates wrote, ‘‘The physician must be acquainted
with many things and assuredly with rubbing’’ (the
ancient Greek term for massage was rubbing).
The roots of modern, scientific massage therapy
go back to Per Henrik Ling (1776–1839), a Swede,
who developed an integrated system consisting of
massage and active and passive exercises. Ling established the Royal Central Gymnastic Institute in
Sweden in 1813 to teach his methods.
2358

Modern, scientific massage therapy was introduced in the United States in the 1850s by two
New York physicians, brothers George and Charles
Taylor, who had studied in Sweden. The first clinics
for massage therapy in the United States were opened
by two Swedish physicians after the Civil War period.
Doctor Baron Nils Posse operated the Posse Institute
in Boston and Doctor Hartwig Nissen opened
the Swedish Health Institute near the Capitol in
Washington, D.C.
Although there were periods when massage fell
out of favor, in the 1960s it made a comeback in a
different way as a tool for relaxation, communication,
and alternative healing. Today, massage is one of the
most popular healing modalities. It is used by conventional, as well as alternative, medical communities and
is now covered by some health insurance plans.
Massage therapy is the scientific manipulation
of the soft tissues of the body for the purpose of
normalizing those tissues and consists of a group of
manual techniques that include applying fixed or
movable pressure, holding, and/or causing movement
of or to the body. While massage therapy is applied
primarily with the hands, sometimes the forearms or
elbows are used. These techniques affect the muscular,
skeletal, circulatory, lymphatic, nervous, and other
systems of the body. The basic philosophy of massage
therapy embraces the concept of vis Medicatrix
naturae, which is aiding the ability of the body to
heal itself, and is aimed at achieving or increasing
health and well-being.
Touch is the fundamental medium of massage
therapy. While massage can be described in terms of
the type of techniques performed, touch is not used
solely in a mechanistic way in massage therapy. One
could look at a diagram or photo of a massage technique that depicts where to place one’s hands and what
direction the stroke should go, but this would not
convey everything that is important for giving a good
massage. Massage also has an artistic component.
Because massage usually involves applying touch
with some degree of pressure and movement, the massage therapist must use touch with sensitivity in order
to determine the optimal amount of pressure to use for
each person. For example, using too much pressure
may cause the body to tense up, while using too little
may not have enough effect. Touch used with sensitivity also allows the massage therapist to receive useful
information via his or her hands about the client’s
body, such as locating areas of muscle tension and
other soft tissue problems. Because touch is also a
form of communication, sensitive touch can convey a
GALE ENCYCLOPEDIA OF MEDICINE

In practice, many massage therapists use more
than one technique or method in their work and sometimes combine several. Effective massage therapists
ascertain each person’s needs and then use the techniques that will meet those needs best.
Swedish massage uses a system of long gliding
strokes, kneading, and friction techniques on the
more superficial layers of muscles, generally in the
direction of blood flow toward the heart, and sometimes combined with active and passive movements of
the joints. It is used to promote general relaxation,
improve circulation and range of motion, and relieve
muscle tension. Swedish massage is the most commonly used form of massage.
Deep tissue massage is used to release chronic
patterns of muscular tension using slow strokes, direct
pressure, or friction directed across the grain of the
muscles. It is applied with greater pressure and to
deeper layers of muscle than Swedish, which is why it
is called deep tissue and is effective for chronic muscular tension.
Sports massage uses techniques that are similar to
Swedish and deep tissue, but are specially adapted to
deal with the effects of athletic performance on the
body and the needs of athletes regarding training,
performing, and recovery from injury.
Neuromuscular massage is a form of deep massage that is applied to individual muscles. It is used
primarily to release trigger points (intense knots of
muscle tension that refer pain to other parts of the
body), and also to increase blood flow. It is often used
to reduce pain. Trigger point massage and myotherapy are similar forms.
Acupressure applies finger or thumb pressure to
specific points located on the acupuncture meridians
(channels of energy flow identified in Asian concepts
of anatomy) in order to release blocked energy along
these meridians that causes physical discomforts, and
re-balance the energy flow. Shiatsu is a Japanese form
of acupressure.
The cost of massage therapy varies according to
geographic location, experience of the massage therapist, and length of the massage. In the United States,
the average range is from $35-60 for a one hour session. Massage therapy sessions at a client’s home or
office may cost more due to travel time for the massage
therapist. Most sessions are one hour. Frequency of
massage sessions can vary widely. If a person is receiving massage for a specific problem, frequency can vary
GALE ENCYCLOPEDIA OF MEDICINE

widely based on the condition, though it usually will
be once a week. Some people incorporate massage into
their regular personal health and fitness program.
They will go for massage on a regular basis, varying
from once a week to once a month.
The first appointment generally begins with information gathering, such as the reason for getting massage therapy, physical condition and medical history,
and other areas. The client is asked to remove clothing
to one’s level of comfort. Undressing takes place in
private, and a sheet or towel is provided for draping.
The massage therapist will undrape only the part of
the body being massaged. The client’s modesty is
respected at all times. The massage therapist may use
an oil or cream, which will be absorbed into the skin in
a short time.
To receive the most benefit from a massage, generally the person being massaged should give the
therapist accurate health information, report discomfort of any kind (whether it is from the massage itself
or due to the room temperature or any other distractions), and be as receptive and open to the process as
possible.
Insurance coverage for massage therapy varies
widely. There tends to be greater coverage in states
that license massage therapy. In most cases, a physician’s prescription for massage therapy is needed.
Once massage therapy is prescribed, authorization
from the insurer may be needed if coverage is not
clearly spelled out in one’s policy or plan.

Preparations
Going for a massage requires little in the way of
preparation. Generally, one should be clean and
should not eat just before a massage. One should not
be under the influence of alcohol or non-medicinal
drugs. Massage therapists generally work by appointment and usually will provide information about how
to prepare for an appointment at the time of making
the appointment.

Precautions
Massage is comparatively safe; however it is generally contraindicated, i.e., it should not be used, if a
person has one of the following conditions: advanced
heart diseases, hypertension (high blood pressure),
phlebitis, thrombosis, embolism, kidney failure, cancer
if massage would accelerate metastasis (i.e., spread
a tumor) or damage tissue that is fragile due to
chemotherapy or other treatment, infectious diseases,
contagious skin conditions, acute inflammation,
2359

Massage therapy

sense of caring—an essential element in the therapeutic relationship—to the person receiving massage.

Massage therapy

infected injuries, unhealed fractures, dislocations,
frostbite, large hernias, torn ligaments, conditions
prone to hemorrhage, and psychosis.
Massage should not be used locally on affected
areas (i.e., avoid using massage on the specific areas of
the body that are affected by the condition) for the
following conditions: rheumatoid arthritis flare up,
eczema, goiter, and open skin lesions. Massage may
be used on the areas of the body that are not affected
by these conditions.
In some cases, precautions should be taken before
using massage for the following conditions: pregnancy,
high fevers, osteoporosis, diabetes, recent postoperative cases in which pain and muscular splinting
(i.e., tightening as a protective reaction) would be
increased, apprehension, and mental conditions that
may impair communication or perception. In such
cases, massage may or may not be appropriate. The
decision on whether to use massage must be based on
whether it may cause harm. For example, if someone
has osteoporosis, the concern is whether bones are
strong enough to withstand the pressure applied.
If one has a health condition and has any hesitation
about whether massage therapy would be appropriate,
a physician should be consulted.

Side effects
Massage therapy does not have side effects.
Sometimes people are concerned that massage may
leave them too relaxed or too mentally unfocused.
To the contrary, massage tends to leave people feeling
more relaxed and alert.

Research and general acceptance
Before 1939, more than 600 research studies on
massage appeared in the main journals of medicine in
English. However, the pace of research was slowed by
medicine’s disinterest in massage therapy.
Massage therapy research picked up again in the
1980s, as the growing popularity of massage paralleled
the growing interest in complementary and alternative
medicine. Well designed studies have documented the
benefits of massage therapy for the treatment of acute
and chronic pain, acute and chronic inflammation,
chronic lymphedema, nausea, muscle spasm, various
soft tissue dysfunctions, anxiety, depression, insomnia, and psycho-emotional stress, which may aggravate mental illness.
Premature infants treated with daily massage
therapy gain more weight and have shorter hospital
stays than infants who are not massaged. A study of
2360

40 low-birth-weight babies found that the 20 massaged
babies had a 47% greater weight gain per day and
stayed in the hospital an average of six days less than
20 infants who did not receive massage, resulting a
cost savings of approximately $3,000 per infant.
Cocaine-exposed, preterm infants given massage
three times daily for a 10 day period showed significant improvement. Results indicated that massaged
infants had fewer postnatal complications and exhibited fewer stress behaviors during the 10 day period,
had a 28% greater daily weight gain, and demonstrated more mature motor behaviors.
A study comparing 52 hospitalized depressed and
adjustment disorder children and adolescents with a
control group that viewed relaxation videotapes,
found massage therapy subjects were less depressed
and anxious, and had lower saliva cortisol levels (an
indicator of less depression).
Another study showed massage therapy produced
relaxation in 18 elderly subjects, demonstrated in
measures such as decreased blood pressure and heart
rate and increased skin temperature.
A combination of massage techniques for 52 subjects with traumatically induced spinal pain led to
significant improvements in acute and chronic pain
and increased muscle flexibility and tone. This study
also found massage therapy to be extremely cost effective, with cost savings ranging from 15-50%. Massage
has also been shown to stimulate the body’s ability to
naturally control pain by stimulating the brain to
produce endorphins. Fibromyalgia is an example of a
condition that may be favorably affected by this effect.
A pilot study of five subjects with symptoms of
tension and anxiety found a significant response to
massage therapy in one or more psycho-physiological
parameters of heart rate, frontalis and forearm extensor electromyograms (EMGs) and skin resistance,
which demonstrate relaxation of muscle tension and
reduced anxiety.
Lymph drainage massage has been shown to be
more effective than mechanized methods or diuretic
drugs to control lymphedema secondary to radical
mastectomy, consequently using massage to control
lymphedema would significantly lower treatment
costs. A study found that massage therapy can have
a powerful effect upon psycho-emotional distress in
persons suffering from chronic inflammatory bowel
disease. Massage therapy was effective in reducing
the frequency of episodes of pain and disability in
these patients.
Massage may enhance the immune system. A
study suggests an increase in cytotoxic capacity
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

American Massage Therapy Association. 820 Davis Street,
Suite 100, Evanston, IL. <http://
www.amtamassage.org>.

Elliot Greene

Mastectomy
Definition
Mastectomy is the surgical removal of the breast
for the treatment or prevention of breast cancer.

Purpose
Mastectomy is performed as a surgical treatment
for breast cancer. The severity of a breast cancer is
evaluated according to a complex system called staging. This takes into account the size of the tumor and
whether it has spread to the lymph nodes, adjacent
tissues, and/or distant parts of the body. A mastectomy usually is the recommended surgery for more
advanced breast cancers. Women with earlier stage
breast cancers, who might also have breast-conserving
surgery (lumpectomy), may choose to have a mastectomy. In the United States, approximately 50,000
women a year undergo mastectomy.
The size, location, and type of tumor are important considerations when choosing the best surgery to
treat breast cancer. The size of the breast also is an
important factor. A woman’s psychological concerns
and lifestyle choices also should be considered when
making a decision.
There are many factors that may make a mastectomy the treatment of choice for a patient. Large
tumors are difficult to remove with good cosmetic
results. This is especially true if the woman has small
breasts. Sometimes multiple areas of cancer are found
in one breast, making removal of the whole breast
necessary. The surgeon sometimes is unable to remove
the tumor with a sufficient amount, or margin, of
GALE ENCYCLOPEDIA OF MEDICINE

normal tissue surrounding it. In this situation, the
entire breast needs to be removed. Recurrence of
breast cancer after a lumpectomy is another indication
for mastectomy.
Radiation therapy is almost always recommended
following a lumpectomy. If a woman is unable to have
radiation, a mastectomy is the treatment of choice.
Pregnant women cannot have radiation therapy
for fear of harming the fetus. A woman with certain
collagen vascular diseases, such as systemic lupus erythematosus or scleroderma, would experience unacceptable
scarring and damage to her connective tissue from radiation exposure. Any woman who has had therapeutic
radiation to the chest area for other reasons cannot
tolerate additional exposure for breast cancer therapy.
The need for radiation therapy after breast conserving surgery may make mastectomy more appealing for
nonmedical reasons. Some women fear radiation and
choose the more extensive surgery so radiation treatment
will not be required. The commitment of time, usually
five days a week for six weeks, may not be acceptable for
other women. This may be due to financial, personal, or
job-related factors. In geographically isolated areas, a
course of radiation therapy may require lengthy travel
and perhaps unacceptable amounts of time away from
family or other responsibilities.
Some women choose mastectomy because they
strongly fear recurrence of the breast cancer, and lumpectomy seems too risky. Keeping a breast that has contained cancer may feel uncomfortable for some patients.
They prefer mastectomy, so the entire breast will be
removed. However, studies have shown that survival
rates for women choosing mastectomy and those undergoing breast-conserving surgery have been the same.
The issue of prophylactic or preventive mastectomy, or removal of the breast to prevent future breast
cancer, is controversial. Women with a strong family
history of breast cancer and/or who test positive for a
known cancer-causing gene may choose to have both
breasts removed. Patients who have had certain types of
breast cancers that are more likely to recur may elect to
have the unaffected breast removed. Although there is
some evidence that this procedure can decrease the
chances of developing breast cancer, it is not a guarantee.
It is not possible to guarantee that all breast tissue has
been removed. There have been cases of breast cancers
occurring after both breasts have been removed.
Studies have shown that women who choose preventive mastectomy generally are satisfied with their
choice, but also believe they lacked enough information before deciding, particularly about the surgery,
genetic testing, and breast reconstruction. A study
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Mastectomy

associated with massage. A study of chronic fatigue
syndrome subjects found that a group receiving massage therapy had lower depression, emotional distress,
and somatic symptom scores, more hours of sleep, and
lower epinephrine and cortisol levels than a control
group.

Mastectomy

Partial
mastectomy
(quadrantectomy)

Simple
mastectomy

Modified radical
mastectomy with
lymph nodes removed

Radical mastectomy
with chest
muscle removed

There are four types of mastectomies: partial mastectomy, or lumpectomy, in which the tumor and surrounding tissue
is removed; simple mastectomy, where the entire breast and some axillary lymph nodes are removed; modified radical
mastectomy, in which the entire breast and all axillary lymph nodes are removed; and the radical mastectomy, where the
entire breast, axillary lymph nodes, and chest muscles are removed. (Illustration by Electronic Illustrators Group.)

released in 2003 concerning women who underwent
radical mastectomy of one breast and chose surgical
removal of the other breast as a preventive measure
found that 83% were highly satisfied with their
decision.

Precautions
The decision to have mastectomy or lumpectomy
should be carefully considered. It is important that the
woman be fully informed of all the potential risks and
benefits of each surgical treatment before making a
choice.

Description
There are several types of mastectomies. The radical mastectomy, also called the Halsted mastectomy, is
rarely performed today. It was developed in the late
1800s, when it was thought that more extensive surgery was most likely to cure cancer. A radical mastectomy involves removal of the breast, all surrounding
lymph nodes up to the collarbone, and the underlying
chest muscle. Women often were left disfigured and
disabled, with a large defect in the chest wall requiring
skin grafting, and significantly decreased arm sensation and motion. Unfortunately, and inaccurately, it
still is the operation many women picture when the
word mastectomy is mentioned.
Surgery that removes breast tissue, nipple, an
ellipse of skin, and some axillary or underarm lymph
nodes, but leaves the chest muscle intact, usually is
2362

called a modified radical mastectomy. This is the most
common type of mastectomy performed today. The
surgery leaves a woman with a more normal chest
shape than the older radical mastectomy procedure,
and a scar that is not visible in most clothing. It also
allows for immediate or delayed breast reconstruction.
In a simple mastectomy, only the breast tissue,
nipple, and a small piece of overlying skin are
removed. If a few of the axillary lymph nodes closest
to the breast also are taken out, the surgery may be
called an extended simple mastectomy.
There are other variations on the term mastectomy. A skin-sparing mastectomy uses special techniques that preserve the patient’s breast skin for use in
reconstruction, although the nipple still is removed.
Total mastectomy is a confusing expression, as it may
be used to refer to a modified radical mastectomy or a
simple mastectomy. In 2003, surgeons reported on a
new technique that spared the nipple in many women
with early stage breast cancer.
Many women choose to have breast reconstruction performed in conjunction with the mastectomy.
The reconstruction can be done using a woman’s own
abdominal tissue, or using saline-filled artificial
expanders, which leave the breast relatively flat but
partially reconstructed. Additionally, there are psychological benefits to coming out of the surgery with
the first step to a reconstructed breast. Immediate
reconstruction will add time and cost to the mastectomy procedure, but the patient can avoid the physical
impact of a later surgery.
GALE ENCYCLOPEDIA OF MEDICINE

The surgery may take from two to five hours.
Patients usually stay at least one night in the hospital,
although outpatient mastectomy is increasingly performed for about 10% of all patients. Insurance
usually covers the cost of mastectomy. If immediate
reconstruction is performed, the length of stay, recovery period, insurance reimbursement, and fees will
vary. In 1998, the Women’s Health and Cancer
Rights Act required insurance plans to cover the cost
of breast reconstruction in conjunction with a mastectomy procedure.

Preparation
Routine preoperative preparations, such as not
eating or drinking the night before surgery, typically
are ordered for a mastectomy. On rare occasions, the
patient also may be asked to donate blood in case a
blood transfusion is required during surgery. The
patient should advise the surgeon of any medications
she is taking. Information regarding expected outcomes and potential complications also should be
part of preparation for a mastectomy, as for any surgical procedure. It is especially important that women
know about sensations they might experience after
surgery, so they are not misinterpreted as a sign of
poor wound healing or recurrent cancer.

Aftercare
In the past, women often stayed in the hospital at
least several days. Now many patients go home the
same day or within a day or two after their mastectomies. Visits from home care nurses can sometimes be
arranged, but patients need to learn how to care for
themselves before discharge from the hospital.
Patients may need to learn to change bandages and/
or care for the incision. The surgical drains must be
attended to properly; this includes emptying the drain,
measuring fluid output, moving clots through the
drain, and identifying problems that need attention
from the doctor or nurse. If the drain becomes
GALE ENCYCLOPEDIA OF MEDICINE

blocked, fluid or blood may collect at the surgical
site. Left untreated, this accumulation may cause
infection and/or delayed wound healing.
After a mastectomy, activities such as driving may
be restricted according to individual needs. Pain is
usually well controlled with prescribed medication.
Severe pain may be a sign of complications, and
should be reported to the physician. A return visit to
the surgeon is usually scheduled 7 to 10 days after the
procedure.
Exercises to maintain shoulder and arm mobility
may be prescribed as early as 24 hours after surgery.
These are very important in restoring strength and
promoting good circulation. However, intense exercise should be avoided for a time after surgery in
order to prevent injury. The specific exercises suggested by the physician will change as healing progresses. Physical therapy is an integral part of care
after a mastectomy, aiding in the overall recovery
process.
Emotional care is another important aspect of
recovery from a mastectomy. A mastectomy patient
may feel a range of emotions including depression,
negative self-image, grief, fear and anxiety about possible recurrence of the cancer, anger, or guilt. Patients
are advised to seek counseling and/or support groups
and to express their emotions to others, whether
family, friends, or therapists. Assistance in dealing
with the psychological effects of the breast cancer
diagnosis, as well as the surgery, can be invaluable
for women.
Measures to prevent injury or infection to the
affected arm should be taken, especially if axillary
lymph nodes were removed. There are a number of
specific instructions directed toward avoiding pressure
or constriction of the arm. Extra care must be exercised to avoid injury, to treat it properly if it occurs,
and to seek medical attention promptly when
appropriate.
Additional treatment for breast cancer may be
necessary after a mastectomy. Depending on the type
of tumor, lymph node status, and other factors, chemotherapy, radiation therapy, and/or hormone therapy may be prescribed.

Risks
Risks that are common to any surgical procedure
include bleeding, infection, anesthesia reaction, or
unexpected scarring. After mastectomy and axillary
lymph node dissection, a number of complications
are possible. A woman may experience decreased
2363

Mastectomy

A mastectomy typically is performed in a hospital
setting, but specialized outpatient facilities sometimes
are used. The surgery is done under general anesthesia.
The type and location of the incision may vary according to plans for reconstruction or other factors, such as
old scars. As much breast tissue as possible is removed.
Approximately 10 to 20 axillary lymph nodes usually
are removed. All tissue is sent to the pathology laboratory for analysis. If no immediate reconstruction is
planned, surgical drains are left in place to prevent
fluid accumulation. The skin is sutured and bandages
are applied.

Mastitis

Resources

KEY TERMS
Axillary—Located in or near the armpit.
Lymphedema—Swelling caused by an accumulation of fluid from faulty lymph drainage.
Mastectomy, modified radical—Total mastectomy
with axillary lymph node dissection, but with
preservation of the pectoral muscles.
Mastectomy, radical—Removal of the breast, pectoral muscles, axillary lymph nodes, and associated
skin and subcutaneous tissue.
Mastectomy, simple—Removal of only the breast
tissue, nipple and a small portion of the overlying
skin

feeling in the back of her armpit or other sensations
including numbness, tingling, or increased skin sensitivity. Some women report phantom breast symptoms,
experiencing itching, aching, or other sensations in the
breast that has been removed. There may be scarring
around where the lymph nodes were removed, resulting in decreased arm mobility and requiring more
intense physical therapy.
Approximately 10% to 20% of patients develop
lymphedema after axillary lymph node removal. This
swelling of the arm, caused by faulty lymph drainage,
can range from mild to severe. It can be treated with
elevation, elastic bandages, and specialized physical
therapy. Lymphedema is a chronic condition that
requires continuing treatment. This complication can
arise at any time, even years after surgery. A new
technique called sentinel lymph node mapping and
biopsy often eliminates the need for removing some
or all lymph nodes by testing the first lymph node for
cancer.

Normal results
A mastectomy is performed as the definitive surgical treatment for breast cancer. The goal of the
procedure is that the breast cancer is completely
removed and does not recur.

Abnormal results
An abnormal result of a mastectomy is the incomplete removal of the breast cancer or a recurrence
of the cancer. Other abnormal results include longlasting (chronic) pain or impairment that does not
improve after several months of physical therapy.
2364

PERIODICALS

‘‘American Women Still Having Too Many Mastectomies.’’
Women’s Health Weekly February 6, 2003: 10.
Frost, Marlene, et al. ‘‘Long-term Satisfaction and
Psychological and Social Function Following Bilateral
Prophylactic Mastectomy.’’ Journal of the American
Medical Association July 20, 2000: 319-24.
‘‘Majority Satisfied with Prophylactic Mastectomy
Decision.’’ AORN Journal November 2003: 773.
‘‘Studies Compare Mastectomy, Lumpectomy Survival
Rates.’’ Clinican Reviews January 2003: 24.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
National Lymphedema Network. 2211 Post St., Suite
404, San Francisco, CA 94115-3427. (800) 541-3259
or (415) 921-1306. <http://www.wenet.net/
lymphnet/>.
Y-ME National Organization for Breast Cancer
Information and Support. 18220 Harwood Ave.,
Homewood, IL 60430. 24-hour hotlines: (800) 221-2141
or (708) 799-8228.
OTHER

ibreast.org April 15, 2001. [cited June 12, 2001]. <http://
www.breastcancer.org>.
Living Beyond Breast Cancer April 15, 2001. [cited June 12,
2001]. <http://www.lbbc.org>.

Ellen S. Weber, MSN
Teresa G. Odle

Mastitis
Definition
Mastitis is an infection of the breast. It usually
only occurs in women who are breastfeeding their
babies.

Description
Breastfeeding is the act of allowing a baby to
suckle at the breast to drink the mother’s milk. In the
process, unaccustomed to the vigorous pull and tug of
the infant’s suck, the nipples may become sore,
cracked, or irritated. This creates a tiny opening in
the breast, through which bacteria can enter. The presence of milk, with high sugar content, gives the bacteria an excellent source of nutrition. Under these
GALE ENCYCLOPEDIA OF MEDICINE

Mastitis

conditions, the bacteria are able to multiply, until they
are plentiful enough to cause an infection within the
breast.
Mastitis usually begins more than two to four
weeks after delivery of the baby. It is a relatively
uncommon complication of breastfeeding mothers,
occurring in only approximately 3% to 5% of nursing
women.

Causes and symptoms
The most common bacteria causing mastitis is
called Staphylococcus aureus. In 25-30% of people,
this bacteria is present on the skin lining normal,
uninfected nostrils. It is probably this bacteria, clinging to the baby’s nostrils, that is available to create
infection when an opportunity (crack in the nipple)
presents itself.
Usually, only one breast is involved. An area of
the affected breast becomes swollen, red, hard, and
painful. Other symptoms of mastitis include fever,
chills, and increased heart rate.

Diagnosis
Diagnosis involves obtaining a sample of breast
milk from the infected breast. The milk is cultured,
allowing colonies of bacteria to grow. The causative bacteria then can be specially prepared for
identification under a microscope. At the same
time, tests can be performed to determine what
type of antibiotic would be most effective against
that particular bacteria. Sometimes, women and
their physicians confuse mastitis with breast engorgement, or the tenderness and redness that appears
when milk builds up in the breasts. Mastitis often
can be distinguished if symptoms are accompanied
by fever.

Mastitis is usually caused by a bacterial infection through
a nipple damaged during breastfeeding. (Photograph by
Dr. P. Marazzi, Photo Researchers, Inc. Reproduced by
permission.)

appear in the breastmilk. Warm compresses applied
to the affected breast can be soothing.

Prognosis
Prognosis for uncomplicated mastitis is excellent.
About 10% of women with mastitis will end up with
an abscess within the affected breast. An abscess is a
collection of pus within the breast. This complication
will require a surgical procedure to drain the pus.

Prevention
The most important aspect of prevention involves
good handwashing to try to prevent the infant from
acquiring the Staphylococcus aureus bacteria in the
first place. Keeping the breast clean before breastfeeding also helps prevent infection. Keeping the breasts
from becoming engorged may help prevent mastitis by
preventing plugging of milk ducts.
Resources

Treatment
A number of antibiotics are used to treat mastitis, including cephalexin, amoxicillin, azithromycin, dicloxacillin, and clindamycin. Breastfeeding
usually should be continued, because the rate of
abscess formation (an abscess is a persistent pocket
of pus) in the infected breast goes up steeply among
women who stop breastfeeding during a bout with
mastitis. Most practitioners allow women to take
acetaminophen while nursing, to relieve both fever
and pain. As always, breastfeeding women need to
make sure that any medication they take is also
safe for the baby, since almost all drugs they take
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Hager, W. David. ‘‘Managing Mastitis: Antibiotics Can
Prove Invaluable in the Treatment of Mastitis, but
Before You Prescribe Them, It’s Important to
Distinguish Breast Engorgement from Infectious
Mastitis.’’ Contemporary OB/GYN January 2004:
32–41.
ORGANIZATIONS

La Leche League International. 1400 N. Meacham Rd.,
Schaumburg, IL 60173-4048. (800) 525-3243. <http://
www.lalecheleague.org>.

Rosalyn Carson-DeWitt, MD
Teresa G. Odle
2365

Mastoidectomy

KEY TERMS

Mastocytosis
Definition
Mastocytosis is a disease characterized by the
presence of too many mast cells in various organs
and tissues.

Description
The body has a variety of free-roaming cell populations that function as immunogenic agents. Most
immunogenic cells fall into the category of white
blood cells, but some remain in tissues and are not
found in the blood. Mast cells are such a group.
Mast cells are found primarily in the skin and
digestive system, including the liver and spleen, and
produce histamine, a chemical most famous for its ability to cause itching. Histamine also causes acid indigestion, diarrhea, flushing, heart pounding, headaches, and
can even cause the blood pressure to drop suddenly.
Mastocytosis comes in three forms. Most cases
produce symptoms but do not shorten life expectancy.
The three forms are:


Mastocytoma, a benign skin tumor.



Urticaria pigmentosa, small collections of mast cells
in the skin that manifest as salmon or brown-colored
patches.



Systemic mastocytosis, the collection of mast cells in
the skin, lymph nodes, liver, spleen, gastrointestinal
tract, and bones.

Causes and symptoms
The cause of mastocytosis is unknown. People
with systemic mastocytosis have bone and joint pain.
Peptic ulcers are frequent because of the increased
stomach acid stimulated by histamine. Many patients
with systemic mastocytosis also develop urticaria pigmentosa. These skin lesions itch when stroked and may
become fluid-filled.

Non-steroidal
anti-inflammatory
drugs
(NSAIDs)—Aspirin, ibuprofen, naproxen, and
many others.
Peptic ulcer—Ulcers in the stomach and upper
duodenum (first portion of the small intestine)
caused by stomach acid and a bacterium called
Helicobacter pylori.

alone without systemic disease) also dramatically
clears or improves as adolescence approaches.
Several medications are helpful in relieving symptoms of systemic mastocytosis. Antihistamines and
drugs that reduce stomach acid are frequently needed.
Headaches respond to migraine treatment. A medicine
called cromolyn helps with the bowel symptoms.
Several other standard and experimental medications
have been used.

Prognosis
Mastocytoma and urticaria pigmentosa rarely if
ever, develop into systemic mastocytosis, and both
spontaneously improve over time. Systemic mastocytosis is only symptomatically treated. There is no
known treatment that decreases the number of mast
cells within tissue.
Resources
BOOKS

Austen, K. Frank. ‘‘Diseases of Immediate Type
Hypersensitivity.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Mastoid tympanoplasty see Mastoidectomy

Diagnosis
A biopsy of the skin patches aids diagnosis. An
elevated level of histamine in the urine or blood is also
indicative of mastocytosis.

Treatment
Mastocytoma usually occurs in childhood and
clears-up on its own. Urticaria pigmentosa (present
2366

Mastoidectomy
Definition
Mastoidectomy is a surgical procedure to remove
an infected portion of the bone behind the ear when
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cholesteatoma—A rare but chronic inflammatory
disease in which skin cells and debris collect in the
middle ear, usually as a result of an ear infection.
Mastoid bone—The prominent bone behind the
ear that projects from the temporal bone of the
skull.

Purpose
Mastoidectomy is performed to remove infected
air cells within the mastoid bone caused by mastoiditis,
ear infection, or an inflammatory disease of the middle
ear (cholesteatoma). The cells are open spaces containing air that are located throughout the mastoid bone.
They are connected to a cavity in the upper part of the
bone, which is in turn connected to the middle ear. As
a result, infections in the middle ear can sometimes
spread through the mastoid bone. When antibiotics
cannot clear this infection, it may be necessary to
remove the infected air cells by surgery.
Mastoidectomies are also performed sometimes to
repair paralyzed facial nerves.

Description
Mastoidectomy is performed less often today
because of the widespread use of antibiotics to treat
ear infections.
There are several different types of mastoidectomy:






Simple (or closed). The operation is performed
through the ear or through a cut (incision) behind
the ear. The surgeon opens the mastoid bone and
removes the infected air cells. The eardrum is cut
(incised) to drain the middle ear. Topical antibiotics
are then placed in the ear.
Radical mastoidectomy. The eardrum and most
middle ear structures are removed, but the innermost small bone (the stapes) is left behind so that
a hearing aid can be used later to offset the hearing loss.
Modified radical mastoidectomy. The eardrum and
the middle ear structures are saved, which allows for
better hearing than is possible after a radical
operation.

The wound is then stitched up around a drainage tube, which is removed a day or two later.
The procedure usually takes between two and three
hours.

Mastoiditis—An inflammation of the bone behind
the ear (the mastoid bone) caused by an infection
spreading from the middle ear to the cavity in the
mastoid bone.

Aftercare
Painkillers are usually needed for the first day or
two after the operation. The patient should drink
fluids freely. After the stitches are removed, the
bulky mastoid dressing can be replaced with a smaller
dressing if the ear is still draining. The patient is given
antibiotics for several days.
The patient should tell the doctor if any of the
following symptoms occur:


Bright red blood on the dressing.



Stiff neck or disorientation. These may be signs of
meningitis.



Facial paralysis, drooping mouth, or problems
swallowing.

Risks
Complications do not often occur, but they may
include:


Persistent ear drainage.



Infections, including meningitis or brain abscesses.



Hearing loss.



Facial nerve injury. This is a rare complication.



Temporary dizziness.



Temporary loss of taste on the side of the tongue.

Resources
ORGANIZATIONS

Preparation
The doctor will give the patient a thorough ear,
nose, and throat examination as well as a detailed
hearing test before surgery. Patients are given an injection before surgery to make them drowsy.
GALE ENCYCLOPEDIA OF MEDICINE

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
American Hearing Research Foundation. 55 E. Washington
St., Suite 2022, Chicago, IL 60602. (312) 726-9670.
<http://www.american-hearing.org/>.
2367

Mastoidectomy

medical treatment is not effective. This surgery is
rarely needed today because of the widespread use of
antibiotics.

Mastoiditis

Better Hearing Institute. 515 King Street, Suite 420,
Alexandria, VA 22314. (703) 684-3391.

Carol A. Turkington

Mastoiditis
Definition
Mastoiditis is an infection of the spaces within the
mastoid bone. It is almost always associated with otitis
media, an infection of the middle ear. In the most
serious cases, the bone itself becomes infected.

Description
The mastoid is a part of the side (temporal bone)
of the skull. It can be felt as a bony bump just behind
and slightly above the level of the earlobe. The mastoid has been described as resembling a ‘‘honeycomb’’
of tiny partitioned-off airspaces. The mastoid is connected with the middle ear, so that when there is a
collection of fluid in the middle ear, there is usually
also a slight collection of fluid within the airspaces of
the mastoid.
Mastoiditis can range from a simple case of some
fluid escaping into the mastoid air cells during a middle ear infection, to a more complex infection which
penetrates through to the lining of the mastoid bone,
to a very severe and destructive infection of the mastoid bone itself.

Causes and symptoms
Mastoiditis is caused by the same types of bacteria
which cause middle ear infections (Streptococcus pneumoniae and Haemophilus influenzae), as well as by a
variety of other bacteria (Staphylococcus aureus,
Pseuodomonas aeruginosa, Klebsiella, Escherichia coli,
Proteus, Prevotella, Fusobacterium, Porphyromonas,
and Bacteroides). Mastoiditis may occur due to the
progression of an untreated, or undertreated, middle
ear infection.
Symptoms of mastoiditis may at first be the same
as symptoms of an early middle ear infection. With
progression, however, the swollen mastoid may push
the outer ear slightly forward and away from the head.
The area behind the ear will appear red and swollen,
and will be very sore. There may be drainage of pus
from the infected ear. In some cases, the skin over the
2368

KEY TERMS
Abscess—A pocket of infection, usually including a
collection of pus.
Meningitis—Inflammation and infection of the tissues covering the brain and spinal cord (the
meninges).
Otitis or oteitis—An infection of the middle ear;
marked by an enlargement of bone, tenderness and
dull aching pain.

mastoid may develop an opening through which pus
drains. Fever is common.

Diagnosis
Mastoiditis is usually suspected when a severe
middle ear infection is accompanied by redness, swelling, and pain in the mastoid area. A computed tomography scan (CT scan) will show inflammation and
fluid within the airspaces of the mastoid, as well as the
erosion of the little walls of bone that should separate
the air spaces. If there is any fluid draining from the
ear or mastoid, this can be collected and processed in a
laboratory to allow identification of the causative
organism. If there is no fluid available, a tiny needle
can be used to obtain a sample of the fluid which has
accumulated behind the eardrum.

Treatment
Identification of the causative organism guides
the practitioner’s choice of antibiotic. Depending on
the severity of the infection, the antibiotic can be given
initially through a needle in the vein (intravenously or
IV), and then (as the patient improves) by mouth.
In the case of a very severe infection of the mastoid bone itself, with a collection of pus (abscess), an
operation to remove the mastoid part of the temporal
bone is often necessary (mastoidectomy).

Prognosis
With early identification of mastoiditis, the prognosis is very good. When symptoms are not caught
early enough, however, a number of complications can
occur. These include an infection of the tissues covering the brain and spinal cord (meningitis), a pocket of
infection within the brain (abscess), or an abscess
within the muscles of the neck. All of these complications have potentially more serious prognoses.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention of mastoiditis involves careful and
complete treatment of any middle ear infections.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.

Rosalyn Carson-DeWitt, MD

Maternal serum alpha-fetoprotein test see
Alpha-fetoprotein test

Maternal to fetal infections
Definition
Maternal to fetal infections are transmitted from
the mother to her fetus, either across the placenta
during fetal development (prenatal) or during labor
and passage through the birth canal (perinatal).

Description
Antibodies in the maternal blood prevent most
infections from being transmitted to the fetus.
However some maternal-to-fetal infections, particularly in the first trimester of pregnancy, can cause
miscarriage or severe birth defects. Other infections
can cause preterm labor, fetal or neonatal death, or
serious illness in newborns. Perinatal transmissions
infect the fetus after its protective membranes rupture—the waters break—and during labor and delivery when the fetus is exposed to maternal blood.
Perinatal transmission is more likely if the waters
break prematurely.
Toxoplasmosis
Up to one-third of all people are infected with
toxoplasmosis. The U.S. Centers for Disease Control
and Prevention (CDC) estimate that 25–45% of
women of childbearing age carry the parasite
Toxoplasma gondii that causes toxoplasmosis. Very
few infected people have symptoms and most pregnant women have antibodies that protect the fetus
from infection. However in one-third of women who
are infected for the first time during pregnancy, the
parasite infects the placenta and enters the fetal circulation. Congenital (present at birth) infection occurs in
GALE ENCYCLOPEDIA OF MEDICINE

one out of every 800–1,400 infants born to infected
mothers. The fetal infection rate is above 60% if
maternal infection occurs during the third trimester,
but the most severe fetal complications occur with
first-trimester infection.
Viral respiratory infections
Cytomegalovirus (CMV) is the most common
infection that can be transmitted to a fetus. From
50–80% of childbearing-age women have been
infected by CMV prior to pregnancy. However about
1–3% of women have their first or primary CMV
infection during pregnancy and about one-third of
these infections are transmitted to fetuses. Although
most infants with congenital CMV have no problems,
infection in early pregnancy can cause miscarriage or
birth defects and CMV is a leading cause of congenital
deafness. In later pregnancy CMV infection may cause
preterm labor, stillbirth, or serious newborn illness. In
the United States about 8,000 infants annually are
born with potentially fatal CMV-related birth defects.
Fifth disease, caused by the parvovirus B19, is very
common among children. About one-half of all adults
are susceptible. About one-third of infants whose
mothers contract fifth disease during pregnancy
show signs of infection at birth. Although not usually
dangerous, fifth disease contracted early in pregnancy
can cause miscarriage or severe fetal anemia (low
blood count) that can lead to congestive heart failure.
A fetus infected from its mother by Varicella zoster virus may develop pocks that can cause limb deformities early in development. If a woman contracts
varicella (chickenpox) during the first 20 weeks of
pregnancy, there is a 2% chance that her newborn
will have varicella syndrome. However the greatest
risk from varicella is if the mother contracts the virus
just before delivery when she has not yet produced
antibodies to protect the newborn.
In the past rubella was a common cause of birth
defects. However routine vaccinations have made prenatal infection rare in the developed world. Rubella
infection during the first 10 weeks of pregnancy may
cause fetal death and more than 50% of newborns
have severe birth defects. Infections contracted later
in pregnancy do not cause congenital defects,
although the newborn may become seriously ill and
eventually develop diabetes mellitus.
Bacterial infections
Invasive group B streptococcal (GBS) disease is
the most common cause of life-threatening infection in
newborns. Up to 20% of pregnant women carry GBS
2369

Maternal to fetal infections

Prevention

Maternal to fetal infections

in their vaginas during the last trimester, with the
potential of infecting the fetus during birth.
Although premature infants are more susceptible to
GBS, 75% of infected infants are full-term. During the
1970s GBS emerged as the most common cause of
newborn sepsis, or blood infection, and meningitis—
infection of the fluid and lining surrounding the brain.
GBS also is a frequent cause of newborn pneumonia.
Maternal infection at conception or within the first
two weeks of pregnancy may lead to hearing and
vision loss and mental retardation. Between 1993 and
2002 congenital GBS infection in the United States
decreased from 1.7 per 1,000 live births to 0.4 per
1,000 due to the use of antibiotics during delivery.

Genital herpes are caused by herpes simplex virus
(HSV) type-2 and, less frequently, by HSV type-1 that
usually causes cold sores. About 25% of American
adults are infected with HSV-2, affecting one in
1,800–5,000 live births. There is little risk of fetal
transmission if the mother is infected before the third
trimester and has no genital sores at the time of delivery. However infection during the third trimester—
when the virus is likely to be active and the mother
has not yet made sufficient antibodies to protect her
fetus—may lead to congenital HSV infection. This can
seriously damage the newborn’s eyes, central nervous
system, and internal organs, lead to mental retardation and, rarely, death.

The food-borne bacterial infections listeriosis—
caused by Listeria monocytogenes—and salmonellosis
or food poisoning—caused by Salmonella bacteria—
can be transmitted to a fetus. Listeria monocytogenes is
ubiquitous in soil and groundwater, on plants, and in
animals. Most human infections result from ingesting
contaminated foods. Hormonal changes make pregnant women about 20 times more likely than other
healthy adults to contract listeriosis and about onethird of all cases occur in pregnant women. Listeriosis
can cause miscarriage, fetal or newborn death, premature delivery, or severe illness in the mother and infant.

Genital or venereal warts are caused by some
types of human papillomavirus (HPV). At least
20 million Americans are infected and about 5.5 million
new cases are reported annually. Genital warts are
highly infectious and tend to grow faster during pregnancy. If vaginal warts are very large they may interfere
with the infant’s passage through the birth canal, necessitating a cesarean section (C-section).

Each year an estimated 8,000 pregnant women in
the United States are infected with syphilis caused by
the spirochete Treponema pallidum. Rising rates of
syphilis among pregnant women are increasing the
number of infants born with congenital syphilis.
Congenital syphilis is a severe, disabling, and often
life-threatening disease that can cause facial deformity, blindness, and deafness.
Every year in the United States an estimated
40,000 pregnant women are infected with gonorrhea—caused by Neisseria gonorrhoeae—and an estimated 200,000 are infected with chlamydia—caused
by Chlamydia trachomatis. Chlamydia can cause premature membrane rupture and labor. Both infections
can cause newborn conjunctivitis—a discharge of pus
from the eyes.
Sexually transmitted viral infections
Each year an estimated 8,000 pregnant American
women are infected with HIV, the human immunodeficiency virus that causes acquired immune deficiency
syndrome (AIDS). About 20–25% of pregnant women
with untreated HIV transmit it to their fetuses. In
developed countries widespread HIV testing and antiretroviral therapy have reduced maternal-fetal transmission dramatically.
2370

An estimated 8,000 pregnant women are infected
with hepatitis B in the United States every year. They
are at risk for premature delivery and, if untreated,
newborns may develop chronic liver disease.

Causes and symptoms
Toxoplasmosis
The single-celled protozoan Toxoplasma gondii
produces eggs in cat intestines. The eggs shed in cat
feces and can survive for up to 18 months in the soil.
Human infection occurs from handling contaminated
soil or feces or by ingesting raw or undercooked meat
from infected animals.
Although the symptoms of toxoplasmosis usually
are very mild or absent, infection occurring early in
fetal development can cause:


premature birth and low birth weight—under 5 lb
(2.3 kg)



slow growth



fever



skin rashes



easy bruising



anemia



a small or
macrocephaly)



fluid in the cavities of the brain (hydrocephaly)

large

head

(microcephaly

or

GALE ENCYCLOPEDIA OF MEDICINE

inflammation of the brain, heart, or lungs



low birth weight



severe or prolonged jaundice



bruising



an enlarged liver and spleen



bluish-red skin lesions



an eye inflammation called choriorectinitis which
can lead to blindness



enlarged lymph nodes



enlarged liver and spleen



severe illness or death shortly after birth



brain inflammation



pneumonia

Symptoms of congenital toxoplasmosis may
appear months or years after birth and may include:

Maternal to fetal infections





seizures or other neurological problems



visual impairment



hearing loss

Although most GBS carriers have no symptoms,
GBS in pregnant women may cause:



mental retardation



bladder or urinary tract infections



infection of the womb



stillbirth

Viral respiratory infections
Although most CMV-infected newborns have no
symptoms, 10–15% may exhibit:

Bacterial infections

Pregnant women are more likely to transmit GBS
to their fetuses if they:



low birth weight



previously delivered a GBS-infected baby



rashes



have a urinary tract infection caused by GBS



small bruises



carry GBS late in pregnancy



jaundice





enlarged liver and spleen

begin labor or membrane rupture before 37 weeks of
gestation



hernias in the groin





microcephaly or hydrocephaly

have membrane rupture 18 hours or more before
delivery

respiratory problems



experience fever during labor




brain damage

From 0.5–15% of CMV-infected infants develop
hearing, vision, or neurological problems over several
years. In addition to crossing the placenta, there is a
1% risk of perinatal CMV transmission.
Symptoms of congenital fifth disease include:


bright red rash on the cheeks



lacy, red rash on the neck, trunk, and legs



joint pain



fatigue



malaise
Varicella syndrome in a newborn is characterized

by:

Symptoms of congenital GBS infection include:


breathing difficulties



shock



sepsis



pneumonia



meningitis

Listeriosis may cause flu-like symptoms and the
infection can be transmitted prenatally even if the
mother has no symptoms.
Symptoms of salmonellosis can be severe in pregnant women and newborns and may include:


diarrhea



fever



abnormally small limbs and head



abdominal cramps



scarring of the skin



rarely, meningitis



eye defects



mental retardation

In addition to various birth defects, newborns
infected with rubella early in the pregnancy may have:
GALE ENCYCLOPEDIA OF MEDICINE

Syphilis can be transmitted to a fetus either prenatally or perinatally if the mother is infected during
pregnancy or was inadequately treated for a past infection. In adults syphilis usually causes genital lesions
10–90 days after exposure, with a rash developing six
2371

Maternal to fetal infections

weeks later. Symptoms may go unnoticed. Congenital
syphilis can cause premature birth or stillbirth.

Symptoms of gonorrhea in women, if present,
may include:

A surviving newborn with untreated congenital
syphilis may have no initial symptoms but may gain
little weight and, during the first month of life,
develop:



bleeding during vaginal intercourse



pain or burning with urination



yellow or bloody vaginal discharge



rash or small fluid-filled blisters on the palms and
soles of the feet



pelvic inflammatory disease



raised bumps around the nose, mouth, and diaper
region



cracks around the mouth



nasal discharge of mucus, pus, or blood



enlarged lymph nodes, liver, and spleen



bone inflammation



rarely, meningitis

Early-stage symptoms of congenital syphilis
include:


failure to thrive



fever



severe congenital pneumonia



rash and lesions around the mouth, genitalia, and
anus



bone lesions



nose cartilage infection or saddle nose (lacking a
bridge)

Symptoms of late-stage congenital syphilis
include:

Sexually transmitted viral infections
HIV can be transmitted through the placenta,
during labor and delivery, and through breast milk.
HIV-infected infants do not have symptoms at birth,
although about 15% develop serious symptoms or
die within the first year. Almost one-half die by the
age of 10.
Factors that may increase the risk of maternal
HIV transmission include:


the mother’s viral load—the amount of HIV in her
blood



use of illicit drugs



severe inflammation of the fetal membranes



a prolonged period between membrane rupture and
delivery

Most women carrying HSV never have recognizable symptoms; however a first episode of genital
herpes during pregnancy can be passed to the fetus
and may cause premature birth. Both HSV-1 and
HSV-2 can be transmitted during birth if the mother
has active genital sores, causing facial or genital herpes
in the newborn.



copper-colored rashes on the face, palms, and soles



scarring around earlier lesions



gray patches on the anus or outer vagina



notched or peg-shaped teeth



joint swelling



bone pain



abnormalities in the lower leg bones



neurological conditions

More serious symptoms of congenital HSV infection include:



visual loss or blindness



a skin rash with small fluid-filled blisters



hearing loss or deafness



chronic or recurring eye and skin infections



cataracts



widespread infection affecting many organs including the lungs and liver



a life-threatening brain infection called herpes
encephalitis

Both gonorrhea and chlamydia can be transmitted
perinatally. Conjunctivitis caused by gonorrhea
usually appears two to seven days after birth.
Conjunctivitis caused by chlamydia usually appears
5–12 days after birth, although sometimes it takes six
weeks to develop.
2372

Initial symptoms of congenital herpes usually
appear within four weeks of birth and may be quite
mild:


blisters on the skin



fever



tiredness



loss of appetite

GALE ENCYCLOPEDIA OF MEDICINE

Although hepatitis B can be transmitted to the
fetus through the placenta, most often it is transmitted
perinatally. Since the virus is thought to pass through
the umbilical cord, C-sections do not prevent transmission. Congenital hepatitis B can cause chronic liver
infection, although symptoms usually do not become
apparent until young adulthood.

Diagnosis
Diagnosis of maternal, fetal, or congenital infection can be difficult. An obstetrician may diagnose a
maternal infection based on the woman’s symptoms
and blood tests. Sometimes a fetal infection can be
diagnosed using ultrasound. Diagnosis of congenital
infections in newborns may be based on a physical
examination, symptoms, and blood or urine tests.
Ultrasound scanning may be used to image the
newborn’s brain and echocardiography may be used
to diagnose heart problems.
Toxoplasmosis
Prenatal tests for toxoplasmosis include:


a blood test for maternal antibodies



testing of the amniotic fluid and fetal blood



fetal ultrasound

Postnatal diagnosis for congenital toxoplasmosis
may include:


antibody tests of the cord blood and cerebrospinal
fluid



an ophthalmologic examination



neurological examinations



a computed axial tomography (CT or CAT) scan

A 2005 study advised that all pregnant women and
newborns have blood screenings for toxoplasmosis



ultrasound for fetal fifth disease



bacterial cultures from blood, spinal fluid, skin, the
vagina, or rectum for GBS



a maternal blood test for listeriosis
Sexually transmitted infections (STIs)

The CDC recommends that all pregnant women
be screened on their first prenatal visit for syphilis,
gonorrhea, chlamydia, HIV, hepatitis B, and hepatitis C.
Infants are tested for syphilis at birth. Syphilis in
an older infant may be diagnosed by a blood test, a
lumbar puncture to look for signs of syphilis in the
brain and central nervous system, an ophthalmologic
examination, dark-field microscopy to visualize the
spirochete, or bone x rays.
Maternal gonorrhea can be diagnosed by staining
or culturing a cervical smear or testing for the bacterial
DNA in a urine or cervical sample.
Women who were not screened for HIV during
pregnancy may be screened during labor or delivery
with a rapid test. The most common screening for HIV
tests for antibodies in the blood; however most infants
born to infected mothers test positive for 6–18 months
because of the presence of maternal antibodies. An
HIV blood test performed within 48 hours of birth
detects only about 40% of infections, so testing is
repeated at one and six months.
An HSV culture from an affected genital site—
preferably on the first day of the outbreak—can test
for herpes simplex. A blood test can show if a person
has ever been infected with HSV and may distinguish
between HSV-1 and HSV-2 and old or recently
acquired infections. An examination or test can indicate whether a pregnant woman has active genital
herpes near the time of delivery.
Genital warts are diagnosed visually. Vinegar may
whiten infected areas to make them more visible.
Cervical warts can be diagnosed by removing a piece
of tissue for microscopic examination.

Treatment
Infants born with serious infections are treated in
the neonatal care unit with intravenous drugs. Infants
born to infected mothers may be treated with medications even if they show few or no signs of infection.

Viral and bacterial infections
Diagnostic procedures include:


blood tests for maternal antibodies against CMV or
fifth disease

GALE ENCYCLOPEDIA OF MEDICINE

Toxoplasmosis
Maternal toxoplasmosis is treated with spiramycin during the first and early second trimesters of
2373

Maternal to fetal infections

Nearly 50% of women infected with HPV have no
symptoms although genital warts may appear weeks
or months after infection. They can become larger
during pregnancy causing difficulty with urination.
Vaginal warts can reduce the elasticity of the vagina
and cause obstruction during delivery. Symptoms of
congenital HPV infection may include lung infection
and obstructed air passages from warts inside the
windpipe.

Maternal to fetal infections

pregnancy. Fetal toxoplasmosis may be treated by
giving the mother pyrimethamine and sulfonamides
such as sulfadiazine during the later second and third
trimesters.

chlamydia is treated with erythromycin eye ointment
and oral tablets.

Newborns with symptoms of toxoplasmosis are
treated with pyrimethamine and sulfadiazine for one
year; leucovorin for one year to protect the bone marrow from pyrimethamine toxicity; corticosteroids
for heart, lung, or eye inflammations; clindamycin;
and a corticosteroid to reduce the inflammation of
chorioretinitis.

Women who are being treated for HIV with combination drugs may stop treatment for the first trimester of pregnancy to avoid the risk of birth defects and
to avoid missing doses due to vomiting, which can
cause the growth of drug-resistant HIV strains.
Although the side effects of the anti-retroviral drugs
may worsen during pregnancy, stopping treatment can
worsen a woman’s condition.

Viral respiratory infections
There is no effective treatment for CMV, although
ganciclovir may be used to treat some symptoms.
Fetal anemia caused by fifth disease may resolve
on its own. If the fetus is at risk for heart failure, a fetal
blood transfusion may be performed. The mother also
may receive medication that passes through the placenta to the fetus.
Exposure to chickenpox or rubella by a nonimmune pregnant woman may be treated with an
injection of immune globulin to help prevent fetal
transmission. Congenital chickenpox is treated immediately to prevent serious complications or death.
There is no specific treatment for rubella infection.
Bacterial infections
Pregnant women with GBS in their urine are treated with penicillin. Most GBS-carriers are treated with
intravenous antibiotics—from membrane rupture
through labor—to prevent fetal transmission. Infants
born with congenital GBS infections are treated immediately with intravenous antibiotics.
Maternal and congenital listeriosis and syphilis
are treated with antibiotics.
Maternal gonorrhea may be treated with cefixime,
ceftriaxone, or levofloxacin. Since women often are
infected with both gonorrhea and chlamydia, a combination of antibiotics such as ceftriaxone and doxycycline or azithromycin are used to treat both
infections.
An antibiotic ointment such as silver nitrate is
placed under the eyelids of all newborns as preventative treatment for gonorrhea. An infant born to a
gonorrhea-infected mother is treated with penicillin.
Conjunctivitis caused by gonorrhea is treated with an
eye ointment containing polymyxin and bacitracin,
erythromycin, or tetracycline. An antibiotic such
as ceftriaxone is given intravenously. Congenital
2374

Viral STIs

Zidovudine (ZDV, AZT, Retrovir) is the only
drug that has been proven to help prevent fetal HIV
infection. HIV-positive pregnant women usually take
ZDV from 14–34 weeks of gestation. During delivery
the mother receives ZDV intravenously. The newborn
is given liquid ZDV every six hours for six weeks. A
2004 study of HIV-positive Thai women found that
oral ZDV beginning at 28 weeks of gestation, with a
single dose of nevirapine during labor, greatly reduces
HIV transmission.
Pneumonia caused by Pneumocystis carinii often
is the first AIDS-related illness to appear in HIVinfected infants and is a major cause of death during
the first year. The CDC recommends that all babies
born to HIV-infected mothers be treated with antipneumonia drugs beginning at four–six weeks and
continuing until the infant is found to be HIVnegative.
Although there is no cure for genital herpes, outbreaks just prior to delivery may be prevented by
acyclovir (Zovirax), famciclovir (Famvir), or valacyclover (Valtrex). An HSV-infected newborn is treated
immediately with intravenous antiviral drugs such as
acyclovir. Eye infections are treated with trifluridine
drops.
There is no cure for HPV and treatment during
pregnancy often is ineffective, although it may include:


Imiquimod cream



5% 5-fluorouracil cream



trichloroacetic acid



freezing or burning the warts with a laser



surgical removal



alpha interferon injected into the wart

HPV infection in newborns is treated by surgically
removing the warts. If the warts obstruct breathing
passages, frequent laser surgery is required. Interferon
may be used to reduce the likelihood of recurrence.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Maternal treatment with spiramycin for toxoplasmosis infection occurring within the first two weeks of
pregnancy prevents transmission to the fetus. The
prognosis for congenital toxoplasmosis depends on
its severity.
With treatment most infants with congenital
CMV survive, although almost all suffer from its
effects.
A GBS-carrier’s risk of delivering an infected
child decreases from one in 200 to one in 4,000 if
she is treated with antibiotics. GBS-infected
mothers are less likely to infect their newborns if
treated with antibiotics during labor. Although
immediate penicillin treatment for GBS-infected
newborns is very effective, about 5% of GBSinfected newborns die.
Many fetuses infected with syphilis early in gestation are stillborn. Nearly 50% of untreated fetuses die
shortly before or after birth. However the fetus is at
minimal risk if the mother receives adequate treatment
with penicillin during pregnancy.
Pregnant women on combined antiretroviral therapy are at a 1–2% risk of transmitting HIV to the
fetus. If the mother’s viral load is under 1,000 and
she is treated with ZDV, the risk of transmission is
almost zero. Mothers with a high viral load may
reduce the risk of transmission by having a C-section
before labor begins and the membranes rupture.
Congenital HIV infection that is treated with combination drugs, including protease inhibitors, may reduce
the risk of death by 67%.
Women with an active HSV infection can reduce
the risk of fetal transmission with a C-section.
Although immediate medication for the newborn
may prevent or reduce the damage from HSV, onehalf of infants born with widespread HSV infections
die and the other one-half may have brain damage.
Infants born to hepatitis B-infected mothers have
a greater-than-95% chance of being protected against
the virus if they receive the first dose of vaccine and
immune globulin within 12 hours of birth.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
General advice for preventing infection during
pregnancy includes:


good hygiene—including frequent thorough hand
washing and not sharing food or drinks—particularly for mothers who have or work with young
children and may be at risk for CMV



vaccinations several months before a planned
pregnancy



appropriate vaccinations after the first trimester of
pregnancy



contacting a healthcare provider immediately upon
being exposed to a transmittable infection

To avoid Taxoplasma during pregnancy women
should:


keep cats indoors



avoid handling cat litter without rubber gloves and
wash thoroughly



disinfect the cat box with boiling water for five minutes



cover sandboxes



wear gloves for gardening and wash afterwards



avoid insects that may have been exposed to cat feces



wash after handling cats, raw meat or poultry, soil,
or sand



avoid raw or undercooked meat and poultry,
unwashed fruits and vegetables, raw eggs, and
unpasteurized milk



kill Taxoplasma by freezing food or cooking it
thoroughly

All non-immune women of childbearing age
should be vaccinated against rubella and chickenpox
before pregnancy. Pregnant women should be tested
for immunity to rubella at their first prenatal visit.
Women should be tested for GBS between 35 and
37 weeks of pregnancy to determine whether the bacteria are likely to be present at delivery.
Since Listeria can grow at temperatures below
408F (48C), pregnant women should handle food cautiously and avoid:


hot dogs and luncheon and deli meats unless they are
reheated to steaming



soft cheeses



refrigerated meat spreads



refrigerated smoked seafood unless it is in a cooked
dish



raw unpasteurized milk
2375

Maternal to fetal infections

Non-infected pregnant women may begin the
hepatitis B vaccine series if they are at high-risk for
infection. Infants born to mothers infected with hepatitis B are given both the first dose of hepatitis B
vaccine and hepatitis B immune globulin within 12
hours of birth. The second and third doses of vaccine
are given at one month and six months of age.

Maternal to fetal infections

KEY TERMS
Antibody—A blood protein produced in response
to a specific foreign substance including bacteria,
viruses, and parasites; the antibody destroys the
organism, providing protection against disease.
Cesarean section; C-section—Incision through the
abdominal and uterine walls to deliver the fetus.
Conjunctivitis—An inflammation of the eye that can
be caused by gonorrhea or chlamydia.
Cytomegalovirus; CMV—A common human herpes
virus that is normally not harmful but may cause
severe complications if transmitted to a fetus.
Fifth disease—Erythema infectiosum; a common
respiratory infection among children caused by
parvovirus B19 that usually is not serious but can
cause fetal complications.
Group B streptococcal (GBS) disease—A common
bacterial infection that is potentially life-threatening
if transmitted to a fetus during early pregnancy or
birth.
Herpes simplex virus; HSV—A very common sexually transmitted infection; Type-2 HSV causes genital
herpes and type-1 HSV usually causes cold sores but
also can cause genital herpes; congenital HSV can
be transmitted to the fetus during birth if the mother
has an active infection.
Human papillomavirus (HPV)—A large family of
viruses, some of which cause genital warts; HPV
can be transmitted to a fetus during birth.
Immune globulin—Serum containing antibodies
against a specific infection.

Pregnant women should use precooked or ready-toeat perishables immediately, clean the refrigerator regularly, and keep the refrigerator at or below 408F (48C).
Salmonellosis may be prevented by:


cooking all meat, poultry, seafood, and eggs
thoroughly



avoiding sushi containing raw fish



washing raw vegetables thoroughly



avoiding unpasteurized milk, soft cheeses, and
alfalfa sprouts

Listeriosis—A food-borne bacterial infection caused
by Listeria monocytogenes to which pregnant
women are particularly susceptible.
Meningitis—An inflammation of the membranes
covering the brain and spinal cord that can be
caused by various congenital infections.
Perinatal infection—A maternal infection that is
transmitted to the fetus after membrane rupture or
during labor or delivery.
Placenta—The uterine organ that provides nourishment to the fetus.
Prenatal infection—A maternal infection that is
transmitted to the fetus through the placenta.
Rubella—German measles; three-day measles; a
viral infection that causes death or severe birth
defects if transmitted to the fetus during the first 10
weeks of gestation.
Salmonellosis—Food poisoning; an infection by
bacteria of the genus Salmonella that usually causes
severe diarrhea and may be transmitted to the fetus.
Sepsis—A systemic or body-wide response to infection.
Sexually transmitted infection; STI—An infectious
disease that is transmitted through sexual activity.
Ultrasound—High-frequency sound waves that are
used to visualize parts of the body or a fetus in the womb.
Varicella—Chickenpox; a disease caused by the
Varicella zoster virus—human herpes virus 3—that
can cause severe birth defects if transmitted to the
fetus during the first 20 weeks of pregnancy and newborn complications if it is transmitted perinatally.



using latex condoms correctly and consistently



avoiding blood-contaminated needles, razors, or
other items

Precautions for preventing fetal exposure to HIVinfected maternal blood include avoiding: amniocentesis, fetal scalp blood sampling, premature rupturing
of the fetal membranes.
Prevention of maternal-to-fetal HSV transmission
includes:


abstaining from sexual activity during the last trimester of pregnancy or if there are signs of an outbreak
or visible sores



using a condom even if no symptoms are present



postponing membrane rupture

Prevention of STIs includes:


abstaining from sexual contact outside of a mutually
monogamous relationship

2376

GALE ENCYCLOPEDIA OF MEDICINE

avoiding a fetal monitor that makes tiny punctures
in the scalp



avoiding vacuum or forceps deliveries which cause
breaks in the infant’s scalp

Resources
BOOKS

Creasy, Robert K., et al. Maternal-Fetal Medicine:
Principles and Practices. 5th ed. London: W. B.
Saunders, 2003.
MacLean, Allan, et al., editors. Infection and Pregnancy.
London: Royal College of Obstetricians and
Gynaecologists, 2001.
PERIODICALS

‘‘Cytomegalovirus; Advances Made in Diagnosis of
Maternal CMV Infection.’’ Women’s Health Weekly
September 2, 2004: 51.
Lallemant, M., et al. ‘‘Single-dose Prenatal Nevirapine
plus Standard Zidovudine to Prevent Mother-toChild Transmission of HIV-1 in Thailand.’’ New
England Journal of Medicine 351, no. 3 (July 15, 2004):
217–28.
Montoya, J. G., and O. Liesenfeld. ‘‘Toxoplasmosis.’’
Lancet 363, no. 9425 (June 12, 2004): 1965-76.
‘‘Parasitology; Preventive Practices Eliminate the Risk for
Congenital Toxoplasmosis.’’ Health & Medicine Week
May 3, 2004: 715.
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th St. SW, PO Box 96920, Washington, DC 200806920. 202-863-2518. <http://www.acog.org>.
American Social Health Association. PO Box 13827,
Research Triangle Park, NC 27709-3827. 800-783-9877.
<http://www.ashastd.org>.
Association of Women’s Health, Obstetric and Neonatal
Nurses. 2000 L Street NW, Suite 740, Washington, DC
20036. 800-673-8499. 202-261-2400.
<http://www.awhonn.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Road, Atlanta, GA 30333. 888-232-3228.
<http://www.cdc.gov>.
Hepatitis B Foundation. 700 East Butler Avenue,
Doylestown, PA 18901-3697. 215-489-4900.
<http://www.hepb.org>.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Avenue, White Plains, NY 10605.
<http://www.marchofdimes.com>.
OTHER

Barss, Vanessa A. Patient Information: Avoiding Infections
in Pregnancy. UpToDate Patient Information.
January 11, 2002 [cited March 15, 2005].
<http://patients.uptodate.com/
topic.asp?file=pregnan/2251>.
Cytomegalovirus (CMV) Infection. National Center for
Infectious Diseases, CDC. October 26, 2002 [cited
GALE ENCYCLOPEDIA OF MEDICINE

February 21, 2005]. <http://www.cdc.gov/ncidod/
diseases/cmv.htm>.
‘‘Genital Herpes.’’ Health Matters. NIAID Fact
Sheet. September 2003 [cited February 21, 2005].
<http://www.niaid.nih.gov/factsheets/
stdherp.htm>.
‘‘Gonorrhea.’’ Health Matters. NIAID Fact Sheet.
October 2004 [cited February 21, 2005].
<http://www.niaid.nih.gov/factsheets/stdgon.htm>.
‘‘Group B Streptococcal Disease (GBS).’’ Disease
Information. Division of Bacterial and Mycotic
Diseases, CDC. February 11, 2004 [cited February 21,
2005]. <http://www.cdc.gov/ncidod/dbmd/
diseaseinfo/groupbstrep_g.htm>.
Herpes Simplex and Pregnancy. International Herpes
Alliance. [Cited February 21, 2005]. <http://
www.herpesalliance.org/resources—04.htm>.
‘‘HIV and AIDS in Pregnancy.’’ Professionals &
Researchers. March of Dimes. November
2002 [cited February 22, 2005].
<http://www.marchofdimes.com/professionals/
681_1223.asp>.
‘‘HIV and Pregnancy.’’ AIDSinfo. Health Information for
Patients, U.S. Department of Health and Human
Services. October 2004 [cited February 22, 2005].
<http://aidsinfo.nih.gov/other/cbrochure/English/
11_en.html>.
‘‘Human Papillomavirus and Genital Warts.’’ Health
Matters. NIAID Fact Sheet. July 2004 [cited February
21, 2005]. <http://www.niaid.nih.gov/factsheets/
stdhpv.htm>.
Listeriosis and Pregnancy: What is Your Risk? Food Safety
and Inspection Service, U.S. Department of
Agriculture. September 2001 [cited March 16, 2005].
<http://www.fsis.usda.gov/OA/pubs/
lm_tearsheet.htm>.
‘‘Mother-To-Infant Transmission.’’ Science. HIV
Prevention Site, Division of AIDS, NIAID. May 21,
2002 [cited February 22, 2005]. <http://www.niaid.
nih.gov/daids/prevention/infant.htm>.
Pregnancy and HIV. AIDS InfoNet. May 2, 2004 [cited
March 16, 2005]. <http://www.aidsinfonet.org/en/doc/
611.doc>.
Pregnant Women and Hepatitis B. Hepatitis B Foundation.
[Cited February 22, 2005]. <http://www.hepb.org/020068.hepb>.
‘‘STDs & Pregnancy.’’ STD Prevention. National Center for
HIV, SID and TB Prevention, CDC. [Cited February
22, 2005]. <http://www.cdc.gov/STDFactSTDs&Pregnancy.htm>.

Margaret Alic, Ph.D.

Mathematics disorder see Learning
disorders
2377

Maternal to fetal infections



Maxillofacial trauma

Maxillofacial trauma
Definition
Maxillofacial trauma refers to any injury to the
face or jaw caused by physical force, foreign objects, or
burns.

Description
Maxillofacial trauma includes injuries to any of
the bony or fleshy structures of the face.
Any part of the face may be affected. Teeth may
be knocked out or loosened. The eyes and their muscles, nerves, and blood vessels may be injured as well as
the eye socket (orbit), which can be fractured by a
forceful blow. The lower jaw (mandible) may be dislocated by force. Although anchored by strong muscles for chewing, the jaw is unstable in comparison
with other bones and is easily dislocated from the
temporomandibular joints that attach it to the skull.
A fractured nose or jaw may affect the ability to
breathe or eat. Any maxillofacial trauma may also
prevent the passage of air or be severe enough to
cause a concussion or more serious brain injury.
Athletes are particularly at risk of maxillofacial
injuries. Boxers suffer repeated blows to the face and
occasional knockouts (traumatic brain injury).
Football, basketball, hockey, and soccer players, and
many other athletes are at risk for milder forms of
brain injury called concussions. There are an estimated 300,000 cases every year. Overall, there are
one million new traumatic brain injuries every year,
causing 50,000 deaths. Of the rest, 7–9% are left with
long-term disability.
Burns to the face are also categorized as maxillofacial trauma.

Causes and symptoms
There are no reliable statistics on the incidence of
maxillofacial trauma because there are so many types
and many are not reported. Automobile accidents are
a major cause, as well as participation in sports, fights,
and other violent acts, and being hit by an object
accidentally, for instance being hit by a baseball
while watching a game. People most at risk are athletes, anyone who drives a vehicle or rides in one, and
those who do dangerous work or engage in aggressive
types of behavior.
One study reported in August 2000 that 42% of all
facial fractures resulted from sports activity.
2378

The major symptoms of most facial injuries are
pain, swelling, bleeding, and bruising, although a fractured jaw also prevents the person from working his
jaw properly, and symptoms of a fractured nose also
include black eyes and possible blockage of the airway
due to swelling and bleeding.
Symptoms of eye injury or orbital fracture can
include blurred or double vision, decreased mobility
of the eye, and numbness in the area of the eye. In
severe injuries there can be temporary or permanent
loss of vision.
Burn symptoms are pain, redness, and possibly
blisters, fever, and headache. Extensive burns can
cause the victim to go into shock. In that situation,
he will have low blood pressure and a rapid pulse.
Symptoms of traumatic brain injury include problems with thinking, memory, and judgement as well
as mood swings, and difficulty with coordination and
balance. These symptoms linger for weeks or months,
and in severe cases can be permanent. Double vision
for months after the injury is not uncommon.

Diagnosis
Trauma is usually diagnosed in an emergency
room or physician’s office by physical examination
and/or x ray. Some injuries require diagnosis by a
specialist. A detailed report of how the injury occurred
is also taken. In some cases, diagnosis cannot be made
until swelling subsides.

Treatment
Treatment varies, depending on the type and
extent of the injury.
Dislocation of the jaw can be treated by a primary
care physician by exerting pressure in the proper manner. If muscle spasm prevents the jaw from moving
back into alignment, a sedative is administered intravenously (IV) to relax the muscles. Afterward, the
patient must avoid opening the jaw wide as he will be
prone to repeat dislocations.
A jaw fracture may be minor enough to heal with
simple limitation of movement and time. More serious
fractures require complicated, multi-step treatment.
The jaw must be surgically immobilized by a qualified
oral or maxillofacial surgeon or an otolaryngologist.
The jaw is properly aligned and secured with metal
pins and wires. Proper alignment is necessary to ensure
that the bite is correct. If the bite is off, the patient may
develop a painful disorder called temporomandibular
joint syndrome.
GALE ENCYCLOPEDIA OF MEDICINE

When the eyes have been exposed to chemicals,
they must be washed out for 15 minutes with clear
water. Contact lenses may be removed only after rinsing the eyes. The eyes should then be kept covered
until the person can be evaluated by a primary care
physician or ophthalmologist.
Face of an elderly woman suffering from maxillofacial
trauma. (Photo Researchers. Reproduced by permission.)

During the weeks of healing the patient is limited
to a liquid diet sipped through a straw and must be
careful not to choke or vomit since he cannot open his
mouth to expel the vomitus. The surgeon will prescribe
pain relievers and perhaps muscle relaxants. Healing
time varies according to the patient’s overall health,
but will take at least several weeks.
Another common maxillofacial fracture is a broken nose. The bones that form the bridge of the nose
may be fractured, but cartilage may also be damaged,
particularly the nasal septum which divides the nose. If
hit from the side, the bones and cartilage are displaced
to the side, but if hit from the front, they are splayed
out. Severe swelling can inhibit diagnosis and treatment. Mild trauma to the nose can sometimes heal
without the person being aware of the fracture unless
there is obvious deformity. The nose will be tender for
at least three weeks.
Either before the swelling begins or after it subsides, some 10 days after the injury, the doctor can
assess the extent of the damage. Physical examination
of the inside using a speculum and the outside, in
addition to a detailed history of how the injury
occurred will determine appropriate treatment. The
doctor should be informed of any previous nasal fractures, nasal surgery, or chronic disease such as osteoporosis. Sometimes an x ray is useful, but it is not
always required.
A primary care physician may treat a nasal fracture himself, but if there is extensive damage or the air
passage is blocked, he will refer the patient to an
otolaryngologist or a plastic surgeon for treatment.
Initially the nose may be packed to control bleeding
and hold the shape. It is reset under anesthesia. A
protective shield or bandage may be placed over it
while the fracture heals.
GALE ENCYCLOPEDIA OF MEDICINE

When a foreign object is lodged in the eye, the
person should not rub the eye or put pressure on it
which would further injure the eyeball. The eye should
be covered to protect it until medical attention can be
obtained.
Several kinds of traumatic injuries can occur to
the mouth. A person can suffer a laceration (cut) to the
lips or tongue, or loosening of teeth, or have teeth
knocked out. Such injuries often accompany a jaw
fracture or other facial injury. Wounds to the soft
tissues of the mouth bleed freely, but the plentiful
blood supply that leads to this heavy bleeding also
helps healing. It is important to clean the wound thoroughly with salt water or hydrogen peroxide rinse to
prevent infection. Large cuts may require sutures, and
should be done by a maxillofacial surgeon for a good
cosmetic result, particularly when the laceration is on
the edge of the lip line (vermilion). The doctor will
prescribe an antibiotic because there is normally a
large amount of bacteria present in the mouth.
Any injury to the teeth should be evaluated by a
dentist for treatment and prevention of infection.
Implantation of a tooth is sometimes possible if it
has been handled carefully and protected. The tooth
should be held by the crown, not the root, and kept in
milk, saline, or contact lens fluid. The patient’s dentist
can refer him to a specialist in this field.
For first degree burns, put a cold-water compress
on the area or run cold water on it. Put a clean bandage
on it for protection. Second and third degree burn
victims must be taken to the hospital for treatment.
Fluids are replaced there through an IV. This is
vital since a patient in shock will die unless those lost
fluids are replaced quickly. Antibiotics are given to
combat infection since the burns make the body vulnerable to infection.
Treatment for a head injury requires examination
by a primary care physician unless symptoms point to
2379

Maxillofacial trauma

In the case of orbital fractures, there is great danger of permanent damage to vision. Double vision and
decreased mobility of the eye are common complications. Surgical reconstruction may be required if the
fracture changes the position of the eye or there is
other facial deformity. Treatment requires a maxillofacial surgeon.

Maxillofacial trauma

a more serious injury. In that case, the victim must
seek emergency care. A concussion is treated with rest
and avoidance of contact sports. Very often athletes
who have suffered a concussion are allowed to play
again too soon, perhaps in the mistaken impression
that the injury is not so bad if the player did not lose
consciousness. Anyone who has had one concussion is
at increased risk of another one.

KEY TERMS
Corneal abrasion—A scratch on the surface of the
eyeball.
Mandible—The lower jaw, a U-shaped bone
attached to the skull at the temporomandibular
joints.

Danger signs that the injury is more serious
include worsening headaches, vomiting, weakness,
numbness, unsteadiness, change in the appearance of
the eyes, seizures, slurred speech, confusion, agitation,
or the victim won’t wake up. These signs require
immediate transport to the hospital. A neurologist
will evaluate the situation, usually with a CT scan. A
stay in a rehabilitation facility may become necessary.

Maxilla—The bone of the upper jaw which serves
as a foundation of the face and supports the orbits.
Orbit—The eye socket which contains the eyeball,
muscles, nerves, and blood vessels that serve the
eye.
Otolaryngologist—Ear, nose and throat specialist.
Shock—A reduction of blood flow in the body
caused by loss of blood and/or fluids. Can be fatal
if not treated quickly.
Temporomandibular
joint—The
mandible
attaches to the temporal bone of the skull and
works like a hinge.

Alternative treatments
Fractures, burns, and deep lacerations require
treatment by a doctor but alternative treatments can
help the body withstand injury and assist the healing
process. Calcium, minerals, vitamins, all part of a
balanced and nutrient-rich diet, as well as regular
exercise, build strong bones that can withstand force
well. After an injury, craniosacral therapy may help
healing and ease the headaches that follow a concussion or other head trauma. A physical therapist can
offer ultrasound that raises temperature to ease pain,
or biofeedback in which the patient learns how to tense
and relax muscles to relieve pain. Hydrotherapy may
ease the stress of recovering from trauma. Chinese
medicine seeks to reconnect the chi along the body’s
meridians and thus aid healing. Homeopathic physicians may prescribe natural medicines such as Arnica
or Symphytum to enhance healing.

Prognosis
When appropriate treatment is obtained quickly
after an injury, the prognosis can be excellent.
However, if the victim of trauma has osteoporosis or
a debilitating chronic disease, healing is more problematic. Healing also depends upon the extent of the
injury. An automobile accident or a gunshot wound,
for example, can cause severe facial trauma that may
require multiple surgical procedures and a considerable
amount of time to heal. Burns and lacerations cause
scarring that might be improved by plastic surgery.

Prevention
Safety equipment is vital to preventing maxillofacial trauma from automobile accidents and sports.
2380

Temporomandibular
joint
syndrome—TMJ
Syndrome refers to an incorrect alignment of the
lower jaw to the skull which causes the bite to be
off line. It causes chronic headaches, nausea, and
other symtoms.
Nasal septum—The cartilage which divides the
nose in half.
Vermilion border—The line between the lip and
the skin.

Here is a partial list of equipment people should
always use:


seatbelts



automobile air bags



approved child safety seats



helmets for riding motorcycles or bicycles, skateboarding, snowboarding, and other sports



safety glasses for the job, yard work, sports



other approved safety equipment for sports such as
mouthguards, masks, and goggles

Resources
PERIODICALS

Perkins, Stephen W. ‘‘The Incidence of Sports-Related
Facial Trauma in Children.’’ Ear, Nose and Throat
Journal August 2000.
Roberts, Graham. ‘‘Dental Emergencies (ABC of Oral
Health).’’ British Medical Journal September 2, 2000.
GALE ENCYCLOPEDIA OF MEDICINE

Measles

ORGANIZATIONS

American Association of Oral & Maxillofacial Surgeons.
9700 W. Bryn Mawr Ave., Rosemont, IL 60018. (847)
678-6200.
Brain Injury Association, Inc. 105 N. Alfred St., Alexandria,
VA 22314. (703) 236-6000. <http://
www.biausa.org.>.
OTHER

‘‘Broken Nose.’’ <http://www.intelihealth.com>.
‘‘Burns: Take Them Seriously.’’ Virtual Hospital.
<http://www.vh.org/Patients/IHB/HealthProse/
Family medicine/burns.html>.
‘‘Fractured Jaw.’’ <http://www.cbshealthwatch.com/cx/
viewarticle/150454>.
‘‘Major Domains of Complementary & Alternative
Medicine.’’ National Institutes of Health.
<http://nccam.nih.gov/fcp/classify/>.

Barbara J. Mitchell

MCS syndrome see Multiple chemical
sensitivity
MD see Muscular dystrophy

Measles
Definition
Measles is an infection caused by a virus, which
causes an illness displaying a characteristic skin rash
known as an exanthem. Measles is also sometimes
called rubeola, 5-day measles, or hard measles.

Description
Measles infections appear all over the world. Prior
to the current effective immunization program, largescale measles outbreaks occurred on a two to threeyear cycle, usually in the winter and spring. Smaller
outbreaks occurred during the off-years. Babies up to
about eight months of age are usually protected from
contracting measles, due to immune cells they receive
from their mothers in the uterus. Once someone has
had measles infection, he or she can never get it again.

Causes and symptoms
Measles is caused by a type of virus called a paramyxovirus. It is an extremely contagious infection,
spread through the tiny droplets that may spray into
the air when an individual carrying the virus sneezes or
coughs. About 85% of those people exposed to the
GALE ENCYCLOPEDIA OF MEDICINE

Measles on child’s face. (Custom Medical Stock Photo.
Reproduced by permission.)

virus will become infected with it. About 95% of those
people infected with the virus will develop the illness
called measles. Once someone is infected with the
virus, it takes about 7–18 days before he or she actually becomes ill. The most contagious time period is
the three to five days before symptoms begin through
about four days after the characteristic measles rash
has begun to appear.
The first signs of measles infection are fever, extremely runny nose, red, runny eyes, and a cough. A few
days later, a rash appears in the mouth, particularly on
the mucous membrane which lines the cheeks. This
rash consists of tiny white dots (like grains of salt or
sand) on a reddish bump. These are called Koplik’s
spots, and are unique to measles infection. The throat
becomes red, swollen, and sore.
A couple of days after the appearance of the
Koplik’s spots, the measles rash begins. It appears in
a characteristic progression, from the head, face, and
neck, to the trunk, then abdomen, and next out along
the arms and legs. The rash starts out as flat, red
patches, but eventually develops some bumps. The
rash may be somewhat itchy. When the rash begins
to appear, the fever usually climbs higher, sometimes
reaching as high as 1058F (40.58C). There may be
nausea, vomiting, diarrhea, and multiple swollen
lymph nodes. The cough is usually more problematic
at this point, and the patient feels awful. The rash
usually lasts about five days. As it fades, it turns a
brownish color, and eventually the affected skin
becomes dry and flaky.
Many patients (about 5–15%) develop other complications. Bacterial infections, such as ear infections,
sinus infections, and pneumonia are common, especially in children. Other viral infections may also strike
the patient, including croup, bronchitis, laryngitis, or
2381

Measles

In addition, the mother’s illness may progress to
pneumonia.

Diagnosis

A transmission electron microscopy (TEM) image of a single
measles virion. (Custom Medical Stock Photo. Reproduced by
permission.)

viral pneumonia. Inflammation of the liver, appendix,
intestine, or lymph nodes within the abdomen may
cause other complications. Rarely, inflammations of
the heart or kidneys, a drop in platelet count (causing
episodes of difficult-to-control bleeding), or reactivation of an old tuberculosis infection can occur.
An extremely serious complication of measles
infection is swelling of the brain. Called encephalitis,
this can occur up to several weeks after the basic
measles symptoms have resolved. About one out of
every thousand patients develops this complication,
and about 10-15% of these patients die. Symptoms
include fever, headache, sleepiness, seizures, and
coma. Long-term problems following recovery from
measles encephalitis may include seizures and mental
retardation.
A very rare complication of measles can occur up
to 10 years following the initial infection. Called subacute sclerosing panencephalitis, this is a slowly progressing, smoldering swelling and destruction of the
entire brain. It is most common among people who
had measles infection prior to the age of two years.
Symptoms include changes in personality, decreased
intelligence with accompanying school problems,
decreased coordination, involuntary jerks and movements of the body. The disease progresses so that the
individual becomes increasingly dependent, ultimately
becoming bedridden and unaware of his or her surroundings. Blindness may develop, and the temperature may spike (rise rapidly) and fall unpredictably as
the brain structures responsible for temperature regulation are affected. Death is inevitable.
Measles during pregnancy is a serious disease,
leading to increased risk of a miscarriage or stillbirth.
2382

Measles infection is almost always diagnosed
based on its characteristic symptoms, including
Koplik’s spots, and a rash which spreads from central
body structures out towards the arms and legs. If there
is any doubt as to the diagnosis, then a specimen of
body fluids (mucus, urine) can be collected and combined with fluorescent-tagged measles virus antibodies. Antibodies are produced by the body’s immune
cells that can recognize and bind to markers (antigens)
on the outside of specific organisms, in this case the
measles virus. Once the fluorescent antibodies have
attached themselves to the measles antigens in the
specimen, the specimen can be viewed under a special
microscope to verify the presence of measles virus.

Treatment
There are no treatments available to stop measles
infection. Treatment is primarily aimed at helping the
patient to be as comfortable as possible, and watching
carefully so that antibiotics can be started promptly if a
bacterial infection develops. Fever and discomfort can
be treated with acetaminophen. Children with measles
should never be given aspirin, as this has caused the
fatal disease Reye’s syndrome in the past. A cool-mist
vaporizer may help decrease the cough. Patients
should be given a lot of liquids to drink, in order to
avoid dehydration from the fever.
Some studies have shown that children with
measles encephalitis benefit from relatively large
doses of vitamin A.

Alternative treatment
Botanical immune enhancement (with echinacea,
for example) can assist the body in working through
this viral infection. Homeopathic support also can be
effective throughout the course of the illness. Some
specific alternative treatments to soothe patients
with measles include the Chinese herbs bupleurum
(Bupleurum chinense) and peppermint (Mentha piperita), as well as a preparation made from empty cicada
(Cryptotympana atrata) shells. The itchiness of the
rash can be relieved with witch hazel (Hamamelis
virginiana), chickweed (Stellaria media), or oatmeal
baths. The eyes can be soothed with an eyewash
made from the herb eyebright (Euphrasia officinalis).
Practitioners of ayurvedic medicine recommend ginger
or clove tea.
GALE ENCYCLOPEDIA OF MEDICINE

Antibodies—Cells made by the immune system
which have the ability to recognize foreign invaders (bacteria, viruses), and thus stimulate the
immune system to kill them.
Antigens—Markers on the outside of such organisms as bacteria and viruses, which allow antibodies to recognize foreign invaders.
Encephalitis—Swelling, inflammation of the brain.
Exanthem (plural, exanthems or exanthemata)—A
skin eruption regarded as a characteristic sign of
such diseases as measles, German measles, and
scarlet fever.
Koplik’s spots—Tiny spots occurring inside the
mouth, especially on the inside of the cheek.
These spots consist of minuscule white dots (like
grains of salt or sand) set onto a reddened bump.
Unique to measles.

Prognosis
The prognosis for an otherwise healthy, wellnourished child who contracts measles is usually
quite good. In developing countries, however, death
rates may reach 15–25%. Adolescents and adults
usually have a more difficult course. Women who
contract the disease while pregnant may give birth to
a baby with hearing impairment. Although only 1 in
1,000 patients with measles will develop encephalitis,
10–15% of those who do will die, and about another
25% will be left with permanent brain damage.

Prevention
Measles is a highly preventable infection. A very
effective vaccine exists, made of live measles viruses
which have been treated so that they cannot cause
actual infection. The important markers on the viruses
are intact, however, which causes an individual’s
immune system to react. Immune cells called antibodies are produced, which in the event of a future
infection with measles virus will quickly recognize the
organism, and kill it off. Measles vaccines are usually
given at about 15 months of age; because prior to that
age, the baby’s immune system is not mature enough
to initiate a reaction strong enough to insure long-term
protection from the virus. A repeat injection should be
given at about 10 or 11 years of age. Outbreaks on
college campuses have occurred among unimmunized
or incorrectly immunized students.
GALE ENCYCLOPEDIA OF MEDICINE

Measles vaccine should not be given to a pregnant
woman, however, in spite of the seriousness of gestational measles. The reason for not giving this particular vaccine during pregnancy is the risk of transmitting
measles to the unborn child.
Surprisingly, new cases of measles began being
reported in some countries—including Great
Britain—in 2001 because of parents’ fears about vaccine safety. The combined vaccine for measles,
mumps, and rubella (MMR) was claimed to cause
autism or bowel disorders in some children.
However, the World Health Organization (WHO)
says there is no scientific merit to these claims. The
United Nations expressed concern that unwarranted
fear of the vaccine would begin spreading the disease
in developing countries, and ultimately in developed
countries as well. Parents in Britain began demanding
the measles vaccine as a separate dose and scientists
were exploring that option as an alternative to the
combined MMR vaccine. Unfortunately, several
children died during an outbreak of measles in
Dublin because they had not received the vaccine.
Child mortality due to measles is considered largely
preventable, and making the MMR vaccine widely
available in developing countries is part of WHO’s
strategy to reduce child mortality by two-thirds by the
year 2015.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Viral Infections: Measles.’’ Section 19, Chapter 265. In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Chiba, M. E., M. Saito, N. Suzuki, et al. ‘‘Measles Infection
in Pregnancy.’’ Journal of Infection 47 (July 2003):
40–44.
Jones, G., R. W. Steketee, R. E. Black, et al. ‘‘How Many
Child Deaths Can We Prevent This Year?’’ Lancet 362
(July 5, 2003): 65–71.
McBrien, J., J. Murphy, D. Gill, et al. ‘‘Measles Outbreak in
Dublin, 2000.’’ Pediatric Infectious Disease Journal 22
(July 2003): 580–584.
‘‘Measles—United States, 2000. (From the Centers for
Disease Control and Prevention).’’ Journal of the
American Medical Association 287, no. 9 (March 6,
2002): 1105–1112.
Scott, L. A., and M. S. Stone. ‘‘Viral Exanthems.’’
Dermatology Online Journal 9 (August 2003): 4.
Sur, D. K., D. H. Wallis, and T. X. O’Connell.
‘‘Vaccinations in Pregnancy.’’ American Family
Physician 68 (July 15, 2003): 299–304.
2383

Measles

KEY TERMS

Meckel’s diverticulum

‘‘WHO: Vaccine Fears Could Lead to Unnecessary
Deaths.’’Medical Letter on the CDC & FDA March 17,
2002: 11.
ORGANIZATIONS

American Academy of Pediatrics (AAP). 141 Northwest
Point Boulevard, Elk Grove Village, IL 60007. (847)
434-4000. <http://www.aap.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

Mebendazole see Antihelminthic drugs
Mechanical debridement see Debridement
Mechanical ventilation see Inhalation
therapies

Meckel’s diverticulum
Definition
Meckel’s diverticulum is a congenital pouch
(diverticulum) approximately two inches in length
and located at the lower (distal) end of the small
intestine. It was named for Johann F. Meckel, a
German anatomist who first described the structure.

Description
The diverticulum is most easily described as a
blind pouch that is a remnant of the omphalomesenteric duct or yolk sac that nourished the early embryo.
It contains all layers of the intestine and may have
ectopic tissue present from either the pancreas or
stomach.
The rule of 2s is the classical description. It is
located about 2 ft from the end of the small intestine,
is often about 2 in in length, occurs in about 2% of the
population, is twice as common in males as females,
and can contain two types of ectopic tissue—stomach
or pancreas. Many who have a Meckel’s diverticulum
never have trouble but those that do present in the first
two decades of life and often in the first two years.
There are three major complications that may
result from the development of Meckel’s diverticulum.
The most common problem is inflammation or infection that mimics appendicitis. This diagnosis is defined
at the time of surgery for suspected appendicitis.
2384

Bleeding caused by ectopic stomach tissue that results
in a bleeding ulcer is the second most frequent problem. Bleeding may be brisk or massive. The third
potential complication is obstruction due to intussusception, or a twist around a persistent connection to
the abdominal wall. This problem presents as a small
bowel obstruction, however, the true cause is identified at the time of surgical exploration.
Meckel’s diverticulum is a developmental defect
that is present in about 2% of people, but does not
always cause symptoms. Meckel’s diverticula (plural
of diverticulum) are found twice as frequently in men
as in women. Complications occur three to five times
more frequently in males.

Causes and symptoms
Meckel’s diverticulum is not hereditary. It is a
vestigial remnant of the omphalomesenteric duct, an
embryonic structure that becomes the intestine. As
such, there is no genetic defect or abnormality.
Symptoms usually occur in children under 10
years of age. There may be bleeding from the rectum,
pain and vomiting, or simply tiredness and weakness
from unnoticed blood loss. It is common for a
Meckel’s diverticulum to be mistaken for the much
more common disease appendicitis. If there is obstruction, the abdomen will distend and there will be
cramping pain and vomiting.

Diagnosis
The situation may be so acute that surgery is
needed on an emergency basis. This is often the case
with bowel obstruction. With heavy bleeding or severe
pain, whatever the cause, surgery is required. The finer
points of diagnosis can be accomplished when the
abdomen is open for inspection during a surgical procedure. This situation is called an acute abdomen.
If there is more time (not an emergency situation),
the best way to diagnose Meckel’s diverticulum is with
a nuclear scan. A radioactive isotope injected into the
bloodstream will accumulate at sites of bleeding or in
stomach tissue. If a piece of stomach tissue or a pool of
blood shows up in the lower intestine, Meckel’s diverticulum is indicated.

Treatment
A Meckel’s diverticulum that is causing discomfort, bleeding, or obstruction must be surgically
removed. This procedure is very similar to an
appendectomy.
GALE ENCYCLOPEDIA OF MEDICINE

Appendectomy—The procedure to surgically
remove an appendix.
Appendicitis—Inflammation of the appendix.
Appendix—A portion of intestine attached to the
cecum.
Cecum—The first part of the large bowel.
Congenital—Refers to a disorder which is present
at birth.
Distal—Away from the point of origin.
Ectopic—Tissue found in an abnormal location.

A close-up image of a patient’s small intestine with a
protruding sac. This condition, called Meckel’s
diverticulum, is a congenital abnormality occurring in 2% of
the population, usually males. (Custom Medical Stock Photo.
Reproduced by permission.)

Intussusception—One piece of bowel inside
another, causing obstruction.
Isotope—Any of two or more species of atoms of a
chemical element with the same atomic number
and nearly identical chemical behavior but with
differing atomic mass and physical properties.
Peptic ulcer—A wound in the bowel that can be
caused by stomach acid or a bacterium called
Helicobacter pylori.
Volvulus—A twisted loop of bowel, causing
obstruction.

Prognosis
The outcome after surgery is usually excellent. The
source of bleeding, pain, or obstruction is removed so
the symptoms also disappear. A Meckel’s diverticulum
will not return.
Resources
BOOKS

Aspinall, Richard J., and Simon T. Taylor-Robinson.
Mosby’s Color Atlas & Text of Gastroenterology.
St. Louis: Mosby-Year Book, 2001.
Cousins, Claire, and Ralph Boulton. A Color Handbook of
Gastroenterology. New York: McGraw-Hill, 1999.
Lipsky, Martin S., and Richard Sadovsky. Gastrointestinal
Problems. Philadelphia: Lippincott Williams & Wilkins
Publishers, 2000.
Sanderson, Ian R., and W. Allan Walker. Development of the
Gastrointestinal Tract. Hamilton, Ontario, Canada: B.
C. Decker, 1999.
Stringer, David A., and Paul S. Babyn. Pediatric
Gastrointestinal Imaging and Intervention. 2nd ed.
Hamilton, Ontario, Canada: B. C. Decker, 2000.
PERIODICALS

al Mahmeed, T., J. K. MacFarlane, and D. Filipenko.
‘‘Ischemic Meckel’s diverticulum and acute
appendicitis.’’ Canadian Journal of Surgery 43, no. 2
(2000): 146-47.
GALE ENCYCLOPEDIA OF MEDICINE

Arnio, P., and I. S. Salonen. ‘‘Abdominal disorders arising
from 71 Meckel’s diverticulum.’’ Annals of Surgery and
Gynecology 89, no. 4 (2000): 281-84.
Heider, R., D. M. Warshauer, and K. E. Behrns. ‘‘Inverted
Meckel’s diverticulum as a source of chronic
gastrointestinal blood loss.’’ Surgery 128, no. 1 (2000):
107-08.
Martin, J. P., P. D. Connor, and K. Charles. ‘‘Meckel’s
diverticulum.’’ American Family Physician 61, no. 4
(2000): 1037-42.
Nagler, J., J. L. Clarke, and S. A. Albert. ‘‘Meckel’s
diverticulitis in an elderly man diagnosed by computed
tomography.’’ Journal of Clinical Gastroenterology
30, no. (2000): 87-88.
ORGANIZATIONS

American Academy of Family Physicians. 11400 Tomahawk
Creek Parkway, Leawood, KS 66211-2672. (913)
906-6000. fp@aafp.org. <http://www.aafp.org/>.
American Academy of Pediatrics. 141 Northwest Point
Boulevard, Elk Grove Village, IL 60007-1098. (847)
434-4000. Fax: (847) 434-8000. kidsdoc@aap.org.
<http://www.aap.org/default.htm>.
American College of Gastroenterology. 4900 B South 31st
Street, Arlington, VA 22206. (703) 820-7400. Fax: (703)
931-4520. <http://www.acg.gi.org>.
American College of Surgeons. 633 North St. Clair St.,
Chicago, IL 60611-32311. (312) 202-5000. Fax: (312)
2385

Meckel’s diverticulum

KEY TERMS

Mediastinoscopy

202-5001. postmaster@facs.org. <http://
www.facs.org/>.
American Medical Association. 515 N. State Street,
Chicago, IL 60610. (312) 464-5000.
<http://www.ama-assn.org/>.
OTHER

American Academy of Family Physicians.
<http://www.aafp.org/afp/20000215/1037.html>.
‘‘Meckel’s Diverticulum.’’ Merck Manual.
<http://www.merck.com/pubs/mmanual/section19/
chapter268/268d.htm>.

L. Fleming Fallon, Jr., MD, DrPH

Median nerve entrapment see Carpal
tunnel syndrome

Mediastinoscopy
Definition
Mediastinoscopy is a surgical procedure that
allows physicians to view areas of the mediastinum,
the cavity behind the breastbone that lies between the
lungs. The organs in the mediastinum include the heart
and its vessels, the lymph nodes, trachea, esophagus,
and thymus.
Mediastinoscopy is most commonly used to detect
or stage cancer. It is also ordered to detect infection,
and to confirm diagnosis of certain conditions and
diseases of the respiratory organs. The procedure
involves insertion of an endotracheal (within the trachea) tube, followed by a small incision in the chest. A
mediastinoscope is inserted through the incision. The
purpose of this equipment is to allow the physician to
directly see the organs inside the mediastinum, and to
collect tissue samples for laboratory study.

Purpose
Mediastinoscopy is often the diagnostic method
of choice for detecting lymphoma, including
Hodgkin’s disease. The diagnosis of sarcoidosis (a
chronic lung disease) and the staging of lung cancer
can also be accomplished through mediastinoscopy.
Lung cancer staging involves the placement of the
cancer’s progression into stages, or levels. These stages
help a physician study cancer and provide consistent
definition levels of cancer and corresponding treatments. The lymph nodes in the mediastinum are likely
to show if lung cancer has spread beyond the lungs.
Mediastinoscopy allows a physician to observe and
2386

extract a sample from the nodes for further study.
Involvement of these lymph nodes indicates diagnosis
and stages of lung cancer.
Mediastinoscopy may also be ordered to verify a
diagnosis that was not clearly confirmed by other
methods, such as certain radiographic and laboratory
studies. Mediastinoscopy may also aid in certain surgical biopsies of nodes or cancerous tissue in the mediastinum. In fact, the surgeon may immediately
perform a surgical procedure if a malignant tumor is
confirmed while the patient is undergoing mediastinoscopy, thus combining the diagnostic exam and surgical procedure into one operation when possible.
Although still performed in 2001, advancements
in computed tomography (CT) and magnetic resonance imaging (MRI) techniques, as well as the new
developments in ultrasonography, have led to a
decline in the use of mediastinoscopy. In addition,
better results of fine-needle aspiration (drawing out
fluid by suction) and core-needle biopsy (using a needle to obtain a small tissue sample) investigations,
along with new techniques in thoracoscopy (examination of the thoracic cavity with a lighted instrument
called a thoracoscope) offer additional options in
examining mediastinal masses. Mediastinoscopy may
be required, however, when these other methods cannot be used or when the results they provide are
inconclusive.

Precautions
Because mediastinoscopy is a surgical procedure,
it should only be performed when the benefits of the
exam’s findings outweigh the risks of surgery and
anesthesia. Patients who previously had mediastinoscopy should not receive it again if there is scarring
present from the first exam.
Several other medical conditions, such as
impaired cerebral circulation, obstruction or distortion of the upper airway, or thoracic aortic aneurysm
(abnormal dilation of the thoracic aorta) may also
preclude mediastinoscopy. Anatomic structures that
can be compressed by the mediastinoscope may complicate these pre-existing medical conditions.

Description
Mediastinoscopy is usually performed in a hospital under general anesthesia. An endotracheal tube is
inserted first, after local anesthesia is applied to the
throat. Once the patient is under general anesthesia, a
small incision is made usually just below the neck or at
the notch at the top of the breastbone. The surgeon
GALE ENCYCLOPEDIA OF MEDICINE

Mediastinoscopy

may clear a path and feel the patient’s lymph nodes
first to evaluate any abnormalities within the nodes.
Next, the physician will insert the mediastinoscope
through the incision. The scope is a narrow, hollow
tube with an attached light that allows the surgeon to
see inside the area. The surgeon can insert tools
through the hollow tube to help perform biopsies. A
sample of tissue from the lymph nodes or a mass can
be extracted and sent for study under a microscope or
on to a laboratory for further testing.
In some cases, analysis of the tissue sample which
shows malignancy will suggest the need for immediate
surgery while the patient is already prepared and
under anesthesia. In other cases, the surgeon will
complete the visual study and tissue extraction and
stitch the small incision closed. The patient will remain
in the surgery recovery area until it is determined
that the effects of anesthesia have lessened and it is
safe for the patient to leave the area. The entire procedure should take about an hour, not counting
preparation and recovery time. Studies have shown
that mediastinoscopy is a safe, thorough, and costeffective diagnostic tool with less risk than some
other procedures.

Preparation
Patients are asked to sign a consent form after
having reviewed the risks of mediastinoscopy and
known risks or reactions to anesthesia. The physician
will normally instruct the patient to fast from midnight before the test until after the procedure is completed. A physician may also prescribe a sedative the
night before the exam and before the procedure. Often
a local anesthetic will be applied to the throat to prevent discomfort during placement of the endotracheal
tube.

Aftercare
Following mediastinoscopy, patients will be carefully monitored to watch for changes in vital signs or
indications of complications of the procedure or the
anesthesia. A patient may have a sore throat from the
endotracheal tube, temporary chest pain, and soreness
or tenderness at the site of incision.

Mediastinoscopy is a surgical procedure used to detect
or stage lymphoma or lung cancer. In this procedure, the
surgeon makes an incision below the neck and inserts a
mediastinoscope (a narrow, hollow tube with an attached
light) through it to reach the area behind the breastbone. The
surgeon can then insert tools through the scope to collect
tissue for laboratory analysis. (Illustration by Electronic
Illustrators Group.)



hemorrhage



pneumothorax (air in the pleural space)



recurrent laryngeal nerve injury, causing hoarseness



infection



tumor implantation in the wound



phrenic nerve injury (injury to a thoracic nerve)



esophageal injury



chylothorax (chyle—a milky lymphatic fluid—in the
pleural space)



air embolism (air bubble)



transient hemiparesis (paralysis on one side of the
body)

Risks
Complications from the actual mediastinoscopy
procedure are relatively rare—the overall complication rate in various studies has been 1.3–3.0%.
However, the following complications, in decreasing
order of frequency, have been reported:
GALE ENCYCLOPEDIA OF MEDICINE

The usual risks associated with general anesthesia
also apply to this procedure.
2387

Meditation

KEY TERMS
Endotracheal—Placed within the trachea, also
known as the windpipe.
Hodgkin’s disease—A malignancy of lymphoid tissue found in the lymph nodes, spleen, liver, and
bone marrow.
Lymph nodes—Small round structures located
throughout the body; contain cells that fight
infections.
Pleural space—Space between the layers of the
pleura (membrane lining the lungs and thorax).

Tahara R. W., et al. ‘‘Is There a Role for Routine
Mediastinoscopy in Patients With Peripheral T1 Lung
Cancers?’’ American Journal of Surgery December
2000: 488–491.
ORGANIZATIONS

Alliance for Lung Cancer Advocacy, Support, and
Education. P.O. Box 849, Vancouver, WA 98666. (800)
298-2436. <http://www.alcase.org>.
American Cancer Society. 1599 Clifton Rd. NE, Atlanta,
GA 30329. 800–ACS–2345 <http://www.cancer.org>.
American Lung Association. 1740 Broadway, New York,
NY 10019-4374. 800-LUNG-USA (800-586-4872).
<http://www.lungusa.org>.

Teresa Odle

Sarcoidosis—A chronic disease characterized by
nodules in the lungs, skin, lymph nodes and
bones; however, any tissue or organ in the body
may be affected.
Thymus—An unpaired organ in the mediastinal
cavity that is important in the body’s immune
response.

Meditation
Definition

Normal results
In the majority of procedures performed to diagnose cancer, a normal result involves evidence of
small, smooth, normal-appearing lymph nodes and
no abnormal tissue, growths, or signs of infection. In
the case of lung cancer staging, results are related to
the severity and progression of the cancer.

Abnormal results
Abnormal findings may indicate lung cancer,
tuberculosis, the spread of disease from one body
part to another, sarcoidosis (a disease that causes
nodules, usually affecting the lungs), lymphoma
(abnormalities in the lymph tissues), and Hodgkin’s
disease.
Resources
BOOKS

Fischbach, Frances Talaska. A Manual of Laboratory and
Diagnostic Tests. 6th ed. Philadelphia: Lippincott
Williams and Wilkins, 2000.
Pagana, Kathleen Deska, and Timothy James Pagana.
Mosby’s Manual of Diagnostic and Laboratory Tests.
St. Louis, MO: Mosby, 1998.
PERIODICALS

Deslauriers, Jean, and Jocelyn Gregoire. ‘‘Clinical and
Surgical Staging of Non-Small Cell Lung Cancer.’’
Chest, Supplement (April 2000): 96S–103S.

2388

Meditation is a practice of concentrated focus
upon a sound, object, visualization, the breath, movement, or attention itself in order to increase awareness
of the present moment, reduce stress, promote relaxation, and enhance personal and spiritual growth.

Purpose
Meditation benefits people with or without acute
medical illness or stress. People who meditate regularly have been shown to feel less anxiety and depression. They also report that they experience more
enjoyment and appreciation of life and that their relationships with others are improved. Meditation produces a state of deep relaxation and a sense of balance
or equanimity. According to Michael J. Baime,
‘‘Meditation cultivates an emotional stability that
allows the meditator to experience intense emotions
fully while simultaneously maintaining perspective on
them.’’ Out of this experience of emotional stability,
one may gain greater insight and understanding about
one’s thoughts, feelings, and actions. This insight in
turn offers the possibility to feel more confident and in
control of life. Meditation facilitates a greater sense of
calmness, empathy, and acceptance of self and others.
Meditation can be used with other forms of medical treatment and is an important complementary
therapy for both the treatment and prevention of
many stress-related conditions. Regular meditation
can reduce the number of symptoms experienced by
patients with a wide range of illnesses and disorders.
GALE ENCYCLOPEDIA OF MEDICINE

Maharishi (meaning great sage) brought Eastern culture
into Western consciousness. He emerged in the late
1950s in London and the United States as a missionary in
the cause of Hinduism, the philosophy of which is called
Vedanta—a belief that ‘‘holds that God is to be found in
every creature and object, that the purpose of human life is
to realize the godliness in oneself and that religious truths
are universal.’’
By 1967, the Maharishi became a leader among
flower-children and an anti-drug advocate. The
Maharishi’s sudden popularity was helped along by such
early fans as the Beatles, Mia Farrow, and Shirley
MacLaine. These people, and many others, practiced
Transcendental Meditation (TM), a Hindu-influenced procedure that endures in America to this day.

(Archive. Reproduced by permission.)

Maharishi Mahesh Yogi is one of the most recognized
spiritual leaders of the world. Almost single-handedly, the

Based upon clinical evidence as well as theoretical
understanding, meditation is considered to be one of
the better therapies for panic disorder, generalized
anxiety disorder, substance dependence and abuse,
ulcers, colitis, chronic pain, psoriasis, and dysthymic
disorder. It is considered to be a valuable adjunctive
therapy for moderate hypertension (high blood pressure), prevention of cardiac arrest (heart attack), prevention of atherosclerosis (hardening of arteries),
arthritis (including fibromyalgia), cancer, insomnia,
migraine, and prevention of stroke. Meditation may
also be a valuable complementary therapy for allergies
and asthma because of the role stress plays in these
conditions. Meditative practices have been reported to
improve function or reduce symptoms in patients with
some neurological disorders as well. These include
people with Parkinson’s disease, people who experience fatigue with multiple sclerosis, and people with
epilepsy who are resistant to standard treatment.
Overall, a 1995 report to the National Institutes of
Health on alternative medicine concluded that, ‘‘More
than 30 years of research, as well as the experience of a
large and growing number of individuals and health
GALE ENCYCLOPEDIA OF MEDICINE

When the 1960s drew to a close, the Maharishi
began to fade from public view. The guru still had enough
followers, though, to people the Maharishi International
University, founded in 1971. One of the main draws of
Maharishi International University was the study of TMSidha, an exotic form of Transcendental Meditation.
Sidhas believe that group meditation can elicit the maharishi effect—a force strong enough to conjure world
peace.

care providers, suggests that meditation and similar
forms of relaxation can lead to better health, higher
quality of life, and lowered health care costs. . .’’

Description
Origins
Meditation techniques have been practiced for
millennia. Originally, they were intended to develop
spiritual understanding, awareness, and direct experience of ultimate reality. The many different religious
traditions in the world have given rise to a rich variety
of meditative practices. These include the contemplative practices of Christian religious orders, the
Buddhist practice of sitting meditation, and the whirling movements of the Sufi dervishes. Although meditation is an important spiritual practice in many
religious and spiritual traditions, it can be practiced
by anyone regardless of their religious or cultural
background to relieve stress and pain.
As Western medical practitioners begin to understand the mind’s role in health and disease, there has
been more interest in the use of meditation in
2389

Meditation

M A H A R I S H I M A H E S H Y O G I (1911– )

Meditation

medicine. Meditative practices are increasingly offered
in medical clinics and hospitals as a tool for improving
health and quality of life. Meditation has been used
as the primary therapy for treating certain diseases;
as an additional therapy in a comprehensive treatment plan; and as a means of improving the quality
of life of people with debilitating, chronic, or terminal
illnesses.
Sitting meditation is generally done in an upright
seated position, either in a chair or cross-legged on a
cushion on the floor. The spine is straight yet relaxed.
Sometimes the eyes are closed. Other times the eyes are
open and gazing softly into the distance or at an
object. Depending on the type of meditation, the meditator may be concentrating on the sensation of the
movement of the breath, counting the breath, silently
repeating a sound, chanting, visualizing an image,
focusing awareness on the center of the body, opening
to all sensory experiences including thoughts, or performing stylized ritual movements with the hands.
Movement meditation can be spontaneous and
free-form or involve highly structured, choreographed, repetitive patterns. Movement meditation is
particularly helpful for those people who find it difficult to remain still.
Generally speaking, there are two main types of
meditation. These types are concentration meditation
and mindfulness meditation. Concentration meditation practices involve focusing attention on a single
object. Objects of meditation can include the breath,
an inner or external image, a movement pattern (as in
tai chi or yoga), or a sound, word, or phrase that is
repeated silently (mantra). The purpose of concentrative practices is to learn to focus one’s attention or
develop concentration. When thoughts or emotions
arise, the meditator gently directs the mind back to
the original object of concentration.
Mindfulness meditation practices involve becoming aware of the entire field of attention. The meditator is instructed to be aware of all thoughts, feelings,
perceptions or sensations as they arise in each moment.
Mindfulness meditation practices are enhanced by the
meditator’s ability to focus and quiet the mind. Many
meditation practices are a blend of these two forms.
The study and application of meditation to health
care has focused on three specific approaches: 1. transcendental meditation (TM); 2. The ‘‘relaxation
response,’’ a general approach to meditation developed by Dr. Herbert Benson; and 3. mindfulness
meditation, specifically the program of mindfulnessbased stress reduction (MBSR) developed by Jon
Kabat-Zinn.
2390

Transcendental meditation
TM has its origins in the Vedic tradition of India
and was introduced to the West by Maharishi Mahesh
Yogi. TM has been taught to somewhere between two
and four million people. It is one of the most widely
practiced forms of meditation in the West. TM has
been studied many times; these studies have produced
much of the information about the physiology of
meditation. In TM, the meditator sits with closed
eyes and concentrates on a single syllable or word
(mantra) for 20 minutes at a time, twice a day.
When thoughts or feelings arise, the attention is
brought back to the mantra. According to Charles
Alexander, an important TM researcher, ‘‘During
TM, ordinary waking mental activity is said to
settle down, until even the subtlest thought is transcended and a completely unified wholeness of awareness . . . is experienced. In this silent, self-referential
state of pure wakefulness, consciousness is fully
awake to itself alone. . . .’’ TM supporters believe
that TM practices are more beneficial than other
meditation practices.
The relaxation response
The relaxation response involves a similar form
of mental focusing. Dr. Herbert Benson, one of the
first Western doctors to conduct research on the
effects of meditation, developed this approach after
observing the profound health benefits of a state of
bodily calm he calls ‘‘the relaxation response.’’ In
order to elicit this response in the body, he teaches
patients to focus upon the repetition of a word,
sound, prayer, phrase, or movement activity (including swimming, jogging, yoga, and even knitting) for
10–20 minutes at a time, twice a day. Patients are also
taught not to pay attention to distracting thoughts
and to return their focus to the original repetition.
The choice of the focused repetition is up to the
individual. Instead of Sanskrit terms, the meditator
can choose what is personally meaningful, such as a
phrase from a Christian or Jewish prayer.
Mindfulness meditation
Mindfulness meditation comes out of traditional
Buddhist meditation practices. Psychologist Jon
Kabat-Zinn has been instrumental in bringing this
form of meditation into medical settings. In formal
mindfulness practice, the meditator sits with eyes
closed, focusing the attention on the sensations and
movement of the breath for approximately 45–60
minutes at a time, at least once a day. Informal mindfulness practice involves bringing awareness to every
GALE ENCYCLOPEDIA OF MEDICINE

Dervish—A member of the Sufi order. Their practice of meditation involves whirling ecstatic dance.
Mantra—A sacred word or formula repeated over
and over to concentrate the mind.
Transcendental meditation (TM)—A meditation
technique based on Hindu practices that involves
the repetition of a mantra.

Precautions

Girl in meditation. (Photograph by Robert J. Huffman. Field Mark
Publications. Reproduced by permission.)

activity in daily life. Wandering thoughts or distracting feelings are simply noticed without resisting or
reacting to them. The essence of mindfulness meditation is not what one focuses on but rather the quality
of awareness the meditator brings to each moment.
According to Kabat-Zinn, ‘‘It is this investigative,
discerning observation of whatever comes up in the
present moment that is the hallmark of mindfulness
and differentiates it most from other forms of meditation. The goal of mindfulness is for you to be more
aware, more in touch with life and whatever is happening in your own body and mind at the time it is
happening—that is, the present moment.’’ The
MBSR program consists of a series of classes involving meditation, movement, and group process. There
are over 240 MBSR programs offered in health care
settings around the world.
Meditation is not considered a medical procedure
or intervention by most insurers. Many patients pay
for meditation training themselves. Frequently, religious groups or meditation centers offer meditation
instruction free of charge or for a nominal donation.
Hospitals may offer MBSR classes at a reduced rate
for their patients and a slightly higher rate for the
general public.
GALE ENCYCLOPEDIA OF MEDICINE

Meditation appears to be safe for most people.
There are, however, case reports and studies noting
some adverse effects. Thirty-three to 50% of the people participating in long silent meditation retreats (two
weeks to three months) reported increased tension,
anxiety, confusion, and depression. On the other
hand, most of these same people also reported very
positive effects from their meditation practice. KabatZinn notes that these studies fail to differentiate
between serious psychiatric disturbances and normal
emotional mood swings. These studies do suggest,
however, that meditation may not be recommended
for people with psychotic disorders, severe depression,
and other severe personality disorders unless they are
also receiving psychological or medical treatment.

Side effects
There are no reported side effects from meditation
except for positive benefits.

Research and general acceptance
The scientific study of the physiological effects of
meditation began in the early 1960s. These studies
prove that meditation affects metabolism, the endocrine system, the central nervous system, and the autonomic nervous system. In one study, three advanced
practitioners of Tibetan Buddhist meditation practices
demonstrated the ability to increase ‘‘inner heat’’ as
much as 61%. During a different meditative practice
they were able to dramatically slow down the rate at
which their bodies consumed oxygen. Preliminary
research shows that mindfulness meditation is associated with increased levels of melatonin. These findings
suggest a potential role for meditation in the treatment
and prevention of breast and prostrate cancer.
Despite the inherent difficulties in designing
research studies, there is a large amount of evidence
2391

Meditation

KEY TERMS

Medullary sponge kidney

of the medical benefits of meditation. Meditation is
particularly effective as a treatment for chronic pain.
Studies have shown meditation reduces symptoms of
pain and pain-related drug use. In a four-year followup study, the majority of patients in a MBSR program
reported ‘‘moderate to great improvement’’ in pain as
a result of participation in the program.
Meditation has long been recommended as a
treatment for high blood pressure; however, there is
a debate over the amount of benefit that meditation
offers. Although most studies show a reduction in
blood pressure with meditation, medication is still
more effective at lowering high blood pressure.
Meditation may also be an effective treatment for
coronary artery disease. A study of 21 patients practicing TM for eight months showed increases in their
amount of exercise tolerance, amount of workload,
and a delay in the onset of ST-segment depression.
Meditation is also an important part of Dean
Ornish’s program, which has been proven to reverse
coronary artery disease.
Research also suggests that meditation is effective
in the treatment of chemical dependency. Gelderloos
and others reviewed 24 studies and reported that all of
them showed that TM is helpful in programs to stop
smoking and also in programs for drug and alcohol
abuse.
Studies also imply that meditation is helpful in
reducing symptoms of anxiety and in treating anxiety-related disorders. Furthermore, a study in 1998 of
37 psoriasis patients showed that those practicing
mindfulness meditation had more rapid clearing of
their skin condition, with standard UV light treatment, than the control subjects. Another study found
that meditation decreased the symptoms of fibromyalgia; over half of the patients reported significant
improvement. Meditation was one of several stress
management techniques used in a small study of
HIV-positive men. The study showed improvements
in the T-cell counts of the men, as well as in several
psychological measures of well-being.
Resources
BOOKS

Astin, John A., et al. ‘‘Meditation’’ in Clinician’s
Complete Reference to Complementary and Alternative
Medicine, edited by Donald Novey. St. Louis, MO:
Mosby, 2000.
Baime, Michael J. ‘‘Meditation and Mindfulness’’ in
Essentials of Complementary and Alternative Medicine,
edited Wayne B. Jonas and Jeffrey S. Levin. New York:
Lippencott, Williams and Wilkins, 1999.

2392

ORGANIZATIONS

Insight Meditation Society. 1230 Pleasant, St. Barre, MA
01005. (978) 355-4378. FAX: (978) 355-6398.
<http://www.dharma.org>.
Mind-Body Medical Institute. Beth Israel Deaconess
Medical Center. One Deaconess Road, Boston,
MA 02215. (617) 632-9525.
<http://www.mindbody.harvard.edu>.
OTHER

Videos are available from the organizations listed above.

Linda Chrisman

Medullary sponge kidney
Definition
Medullary sponge kidney is a congenital defect of
the kidneys where the kidneys fill with pools of urine.

Description
One of every 100 to 200 people have some form of
this disease. The kidneys filter urine from the blood
and direct it down tiny collecting tubes toward the
ureters (ducts that carry urine from the kidney to the
bladder). These tiny tubes gradually join together until
they reach the renal pelvis, where the ureters begin. As
the tubes join, they are supposed to get progressively
bigger as they get fewer in number. In medullary
sponge kidney, the tubes are irregular in diameter,
forming pools of urine along the way. These pools
encourage stone formation and infection.

Causes and symptoms
Although some cases of this disorder seem to be
inherited, usually the cause is not known.
The symptoms associated with medullary sponge
kidney are those related to infection and stone passage. Infection causes fever; back and flank pain;
cloudy, frequent, and burning urine; and general discomfort. Stones cause pain in the flank or groin as they
pass. They usually cause some bleeding. The bleeding
may not be visible in the urine, but it is apparent under
a microscope.

Diagnosis
Recurring kidney infections, bleeding, or stones
will prompt x rays of the kidneys. The appearance
GALE ENCYCLOPEDIA OF MEDICINE

Congenital—Present at birth.
Intravenous pyelogram—X rays of the upper urinary system using a contrast agent that is excreted by
the kidneys into the urine.
Thiazide diuretic—A particular class of medication
that encourages urine production.

of medullary sponge kidney on an intravenous
pyelogram (x rays of the upper urinary system) is
characteristic.

American Kidney Foundation. 6110 Executive Boulevard,
#1010, Rockville, M D 20852. 800-638-8299.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010.<http://www.kidney.org>.

J. Ricker Polsdorfer, MD

Medulloblastoma see Brain tumor
Mefloquine see Antimalarial drugs
Megalencephaly see Congenital brain
defects
Melanoma see Malignant melanoma

Treatment
Many people never have trouble with this disorder. For those that do, infections and stones will need
periodic treatment. Infections should be treated with
antibiotics early in order to prevent kidney damage.
Stones may need to be surgically removed. Often,
removal can be accomplished without an incision but
rather by reaching up with instruments through the
lower urinary tract to grab the stones. There is also a
new method of stone treatment called shock wave
lithotripsy. A special machine delivers a focused blast
of shock waves that breaks stones into sand so that
they will pass out naturally. It is considered reasonably safe and usually effective.

Prognosis
Ignoring symptoms can result in progressive
damage to the kidneys and ultimate kidney failure,
but attentive early treatment will preserve kidney
function.

Prevention
Diligent monitoring for infection at regular intervals and at the first symptom will give the best longterm results. By drinking extra liquids, most stones can
be prevented. The most common kind of stones, calcium stones, can be deterred by regularly taking a
medication that encourages urine production (thiazide
diuretic).
Resources
ORGANIZATIONS

American Association of Kidney Patients. 100 S. Ashley Dr.,
#280, Tampa, FL 33602. (800) 749-2257. <http://
www.aakp.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Melioidosis
Definition
Melioidosis is an infectious disease of humans and
animals caused by a gram-negative bacillus found in
soil and water. It has both acute and chronic forms.

Description
Melioidosis, which is sometimes called Pseudomonas pseudomallei infection, is endemic (occurring naturally and consistently) in Southeast Asia, Australia,
and parts of Africa. It was rare in the United States
prior to recent immigration from Southeast Asia.
Melioidosis is presently a public health concern
because it is most common in AIDS patients and
intravenous drug users.

Causes and symptoms
Melioidosis is caused by Pseudomonas pseudomallei, a bacillus that can cause disease in sheep, goats,
pigs, horses, and other animals, as well as in humans.
The organism enters the body through skin abrasions,
burns, or wounds infected by contaminated soil; inhalation of dust; or by eating food contaminated with
P. pseudomallei. Person-to-person transmission is
unusual. Drug addicts acquire the disease from shared
needles. The incubation period is two to three days.
Chronic melioidosis is characterized by osteomyelitis (inflammation of the bone) and pus-filled
abscesses in the skin, lungs, or other organs. Acute
melioidosis takes one of three forms: a localized skin
infection that may spread to nearby lymph nodes; an
infection of the lungs associated with high fever
(1028F/38.98C), headache, chest pain, and coughing;
2393

Melioidosis

KEY TERMS

Ménière’s disease

KEY TERMS
Osteomyelitis—An inflammation of bone or bone
marrow, often caused by bacterial infections.
Chronic melioidosis may cause osteomyelitis.
Septicemia—Bacterial infection of the bloodstream. One form of melioidosis is an acute septicemic infection.

burns, or other open wounds in areas where the disease is common and avoidance of needle sharing
among drug addicts.
Resources
BOOKS

Pollock, Matthew. ‘‘Infections Due to Pseudomonas Species
and Related Organisms.’’ In Harrison’s Principles of
Internal Medicine, edited by Anthony S. Fauci, et al.
New York: McGraw-Hill, 1997.

Rebecca J. Frey, PhD
and septicemia (blood poisoning) characterized by disorientation, difficulty breathing, severe headache, and
an eruption of pimples on the head or trunk. The third
form is most common among drug addicts and may be
rapidly fatal.

Membranous glomerulopathy see Nephrotic
syndrome
Memory loss see Amnesia

Diagnosis
Melioidosis is usually suspected based on the
patient’s history, especially travel, occupational exposure to infected animals, or a history of intravenous
drug. Diagnosis must then be confirmed through
laboratory tests. P. pseudomallei can be cultured from
samples of the patient’s sputum, blood, or tissue fluid
from abscesses. Blood tests, including complement fixation (CF) tests and hemagglutination tests, also help to
confirm the diagnosis. In acute infections, chest x rays
and liver function tests are usually abnormal.

Treatment
Patients with mild or moderate infections are
given a course of trimethoprim-sulfamethoxazole
(TMP/SMX) and ceftazidime by mouth. Patients
with acute melioidosis are given a lengthy course of
ceftazidime followed by TMP/SMX. In patients with
acute septicemia, a combination of antibiotics is administered intravenously, usually tetracycline, chloramphenicol, and TMP/SMX.

Prognosis
The mortality rate in acute cases of pulmonary
melioidosis is about 10%; the mortality rate for the
septicemic form is significantly higher (slightly above
50%). The prognosis for recovery from mild infections
is excellent.

Prevention
There is no form of immunization for melioidosis.
Prevention requires prompt cleansing of scrapes,
2394

Ménière’s disease
Definition
Ménière’s disease is a condition characterized by
recurrent vertigo (dizziness), hearing loss, and tinnitus
(a roaring, buzzing or ringing sound in the ears).

Description
Ménière’s disease was named for the French physician Prosper Ménière, who first described the illness
in 1861. It is an abnormality within the inner ear. A
fluid called endolymph moves in the membranous
labyrinth or semicircular canals within the bony labyrinth inside the inner ear. When the head or body
moves, the endolymph moves, causing nerve receptors
in the membranous labyrinth to send signals to the
brain about the body’s motion. A change in the
volume of the endolymph fluid, or swelling or rupture
of the membranous labyrinth, is thought to result in
Ménière’s disease symptoms.

Causes and symptoms
Causes
The cause of Ménière’s disease is unknown as of
2002; however, scientists are studying several possible
causes, including noise pollution, viral infections, or
alterations in the patterns of blood flow in the structures of the inner ear. Since Ménière’s disease sometimes runs in families, researchers are also looking into
genetic factors as possible causes of the disorder.
GALE ENCYCLOPEDIA OF MEDICINE

A study published in late 2002 reported that there
is a significant increase in the number of CD4 cells in
the blood of patients having an acute attack of
Ménière’s disease. CD4 cells are a subtype of T cells,
which are produced in the thymus gland and regulate
the immune system’s response to infected or malignant
cells. Further research is needed to clarify the role of
these cells in Ménière’s disease.
Another possible factor in the development of
Ménière’s disease is the loss of myelin from the cells
surrounding the vestibular nerve fibers. Myelin is a
whitish fatty material in the cell membrane of the
Schwann cells that form a sheath around certain
nerve cells. It acts like an electrical insulator. A team
of researchers at the University of Virginia reported in
2002 that the vestibular nerve cells in patients with
unilateral Ménière’s disease are demyelinated; that
is, they have lost their protective ‘‘insulation.’’ The
researchers are investigating the possibility that a viral
disease or disorder of the immune system is responsible
for the demyelination of the vestibular nerve cells.
Symptoms
The symptoms of Ménière’s disease are associated
with a change in fluid volume within the labyrinth of
the inner ear. Symptoms include severe dizziness or
vertigo, tinnitus, hearing loss, and the sensation of
pain or pressure in the affected ear. Symptoms appear
suddenly, last up to several hours, and can occur as
often as daily to as infrequently as once a year. A
typical attack includes vertigo, tinnitus, and hearing
loss; however, some individuals with Ménière’s disease
may experience a single symptom, like an occasional
bout of slight dizziness or periodic, intense ringing in
the ear. Attacks of severe vertigo can force the sufferer
to have to sit or lie down, and may be accompanied by
headache, nausea, vomiting, or diarrhea. Hearing tends
to recover between attacks, but becomes progressively
worse over time.
Ménière’s disease usually starts between the ages
of 20 and 50 years; however, it is not uncommon for
GALE ENCYCLOPEDIA OF MEDICINE

elderly people to develop the disease without a previous history of symptoms. Ménière’s disease affects
men and women in equal numbers. In most patients
only one ear is affected but in about 15% both ears are
involved.

Diagnosis
An estimated 3–5 million people in the United
States have Ménière’s disease, and almost 100,000
new cases are diagnosed each year. Diagnosis is
based on medical history, physical examination, hearing and balance tests, and medical imaging with
magnetic resonance imaging (MRI).
Several types of tests may be used to diagnose the
disease and to evaluation the extent of hearing loss. In
patients with Ménière’s disease, audiometric tests
(hearing tests) usually indicate a sensory type of hearing loss in the affected ear. Speech discrimination or
the ability to distinguish between words that sound
alike is often diminished. In about 50% of patients, the
balance function is reduced in the affected ear. An
electronystagnograph (ENG) may be used to evaluate
balance. Since the eyes and ears work together
through the nervous system to coordinate balance,
measurement of eye movements can be used to test
the balance system. For this test, the patient is seated
in a darkened room and recording electrodes, similar
to those used with a heart monitor, are placed near the
eyes. Warm and cool water or air are gently introduced into the each ear canal and eye movements are
recorded.
Another test that may be used is an electrocochleograph (EcoG), which can measure increased
inner ear fluid pressure.

Treatment
There is no cure for Ménière’s disease, but medication, surgery, and dietary and behavioral changes,
can help control or improve the symptoms.
Medications
Symptoms of Ménière’s disease may be treated
with a variety of oral medicine or through injections.
Antihistamines, like diphenhydramine, meclizine, and
cyclizine can be prescribed to sedate the vestibular
system. A barbiturate medication like pentobarbital
may be used to completely sedate the patient and
relieve the vertigo. Anticholinergic drugs, like atropine
or scopolamine, can help minimize nausea and vomiting. Diazepam has been found to be particularly effective for relief of vertigo and nausea in Ménière’s
2395

Ménière’s disease

One area of research that shows promise is the
possible relationship between Ménière’s disease and
migraine headache. Dr. Ménière himself suggested the
possibility of a link, but early studies yielded conflicting results. A rigorous German study published in late
2002 reported that the lifetime prevalence of migraine
was 56% in patients diagnosed with Ménière’s disease
as compared to 25% for controls. The researchers
noted that further work is necessary to determine the
exact nature of the relationship between the two
disorders.

Ménière’s disease

disease. There have been some reports of successful
control of vertigo after antibiotics (gentamicin or
streptomycin) or a steroid medication (dexamethasone) are injected directly into the inner ear. Some
researchers have found that gentamicin is effective in
relieving tinnitus as well as vertigo.
A newer medication that appears to be effective in
treating the vertigo associated with Ménière’s disease
is flunarizine, which is sold under the trade name
Sibelium. Flunarizine is a calcium channel blocker
and anticonvulsant that is presently used to treat
Parkinson’s disease, migraine headache, and other
circulatory disorders that affect the brain.
Surgical procedures
Surgical procedures may be recommended if the
vertigo attacks are frequent, severe, or disabling and
cannot be controlled by other treatments. The most
common surgical treatment is insertion of a small tube
or shunt to drain some of the fluid from the canal. This
treatment usually preserves hearing and controls vertigo in about one-half to two-thirds of cases, but it is
not a permanent cure in all patients.
The vestibular nerve leads from the inner ear to
the brain and is responsible for conducting nerve
impulses related to balance. A vestibular neurectomy
is a procedure where this nerve is cut so the distorted
impulses causing dizziness no longer reach the brain.
This procedure permanently cures the majority of
patients and hearing is preserved in most cases.
There is a slight risk that hearing or facial muscle
control will be affected.
A labyrinthectomy is a surgical procedure in
which the balance and hearing mechanism in the
inner ear are destroyed on one side. This procedure is
considered when the patient has poor hearing in the
affected ear. Labyrinthectomy results in the highest
rates of control of vertigo attacks, however, it also
causes complete deafness in the affected ear.

Alternative treatment
Changes in diet and behavior are sometimes
recommended. Eliminating caffeine, alcohol, and salt
may relieve the frequency and intensity of attacks in
some people with Ménière’s disease. Reducing stress
levels and eliminating tobacco use may also help.
Acupuncture is an alternative treatment that has
been shown to help patients with Ménière’s disease.
The World Health Organization (WHO) lists
Ménière’s disease as one of 104 conditions that can
be treated effectively with acupuncture.
2396

KEY TERMS
Myelin—A whitish fatty substance that acts like an
electrical insulator around certain nerves in the
peripheral nervous system. It is thought that the
loss of the myelin surrounding the vestibular nerves
may influence the development of Ménière’s
disease.
T cell—A type of white blood cell produced in the
thymus gland that regulates the immune system’s
response to diseased or malignant cells. It is possible that a subcategory of T cells known as CD4 cells
plays a role in Ménière’s disease.
Tinnitus—A roaring, buzzing or ringing sound in
the ears.
Transcutaneous electrical nerve stimulation
(TENS)—A treatment in which a mild electrical
current is passed through electrodes on the skin to
stimulate nerves and block pain signals.
Vertigo—The medical term for dizziness or a spinning sensation.

Prognosis
Ménière’s disease is a complex and unpredictable
condition for which there is no cure. The vertigo associated with the disease can generally be managed or
eliminated with medications and surgery. Hearing
tends to become worse over time, and some of the
surgical procedures recommended, in fact, cause
deafness.

Prevention
Since the cause of Ménière’s disease is unknown as
of 2002, there are no current strategies for its prevention. Research continues on the environmental and
biological factors that may cause Ménière’s disease
or induce an attack, as well as on the physiological
components of the fluid and labyrinth system involved
in hearing and balance. Preventive strategies and more
effective treatment should become evident once these
mechanisms are better understood.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Ballester, M., P. Liard, D. Vibert, and R. Hausler.
‘‘Ménière’s Disease in the Elderly.’’ Otology and
Neurotology 23 (January 2002): 73–78.
Corvera, J., G. Corvera-Behar, V. Lapilover, and A.
Ysunza. ‘‘Objective Evaluation of the Effect of
Flunarizine on Vestibular Neuritis.’’ Otology and
Neurotology 23 (November 2002): 933–937.
Friberg, U., and H. Rask-Andersen. ‘‘Vascular Occlusion in
the Endolymphatic Sac in Ménière’s Disease.’’ Annals
of Otology, Rhinology, and Laryngology 111 (March
2002): 237–245.
Fung, K., Y. Xie, S. F. Hall, et al. ‘‘Genetic Basis of Familial
Ménière’s Disease.’’ Journal of Otolaryngology 31
(February 2002): 1–4.
Ghosh, S., A. K. Gupta, and S. S. Mann. ‘‘Can
Electrocochleography in Ménière’s Disease Be
Noninvasive?’’ Journal of Otolaryngology 31
(December 2002): 371–375.
Mamikoglu, B., R. J. Wiet, T. Hain, and I. J. Check.
‘‘Increased CD4+ T cells During Acute Attack of
Ménière’s Disease.’’ Acta Otolaryngologica 122
(December 2002): 857–860.
Radtke, A., T. Lempert, M. A. Gresty, et al. ‘‘Migraine and
Ménière’s Disease: Is There a Link?’’ Neurology 59
(December 10, 2002): 1700–1704.
Spencer, R. F., A. Sismanis, J. K. Kilpatrick, and W. T.
Shaia. ‘‘Demyelination of Vestibular Nerve Axons in
Unilateral Ménière’s Disease.’’ Ear, Nose and Throat
Journal 81 (November 2002): 785–789.
Steenerson, Ronald L., and Gaye W. Cronin. ‘‘Treatment of
Tinnitus with Electrical Stimulation.’’ OtolaryngologyHead and Neck Surgery 121 (November 1999): 511–513.
Yetiser, S., and M. Kertmen. ‘‘Intratympanic Gentamicin in
Ménière’s Disease: The Impact on Tinnitus.’’
International Journal of Audiology 41 (September 2002):
363–370.

Meningitis
Definition
Meningitis is a serious inflammation of the
meninges, the thin, membranous covering of the
brain and the spinal cord. Meningitis is most commonly caused by infection (by bacteria, viruses, or
fungi), although it can also be caused by bleeding
into the meninges, cancer, diseases of the immune
system, and an inflammatory response to certain
types of chemotherapy or other chemical agents. The
most serious and difficult-to-treat types of meningitis
tend to be those caused by bacteria. In some cases,
meningitis can be a potentially fatal condition.

Description
Meningitis is a particularly dangerous infection
because of the very delicate nature of the brain.
Brain cells are some of the only cells in the body that,
once killed, will not regenerate themselves. Therefore,
if enough brain tissue is damaged by an infection,
serious, life-long handicaps will remain.
In order to learn about meningitis, it is important
to have a basic understanding of the anatomy of the
brain. The meninges are three separate membranes,
layered together, which encase the brain and spinal
cord:


The dura is the toughest, outermost layer, and is
closely attached to the inside of the skull.



The middle layer, the arachnoid, is important
because of its involvement in the normal flow of the
cerebrospinal fluid (CSF), a lubricating and nutritive
fluid that bathes both the brain and the spinal cord.



The innermost layer, the pia, helps direct blood
vessels into the brain.



The space between the arachnoid and the pia contains CSF, which helps insulate the brain from
trauma. Many blood vessels course through this
space.

ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
Ménière’s Network. 2000 Church St., P.O. Box 111,
Nashville, TN 37236. (800) 545-4327. <http://
www.healthy.net/pan/cso/cioi/mn.htm>.
On-Balance, A Support Group for People with Ménière’s
Disease. <http://www.midwestear.com/onbal.htm>.
Vestibular Disorders Association. P.O. Box 4467, Portland,
OR 97208-4467. (800) 837-8428.

Altha Roberts Edgren
Rebecca J. Frey, PhD

Meningioma see Brain tumor
GALE ENCYCLOPEDIA OF MEDICINE

Meningitis

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II. ‘‘CAM Therapies for Specific Conditions:
Ménière’s Disease.’’ New York: Simon & Schuster,
2002.

CSF, produced within specialized chambers deep
inside the brain, flows over the surface of the brain and
spinal cord. This fluid serves to cushion these relatively
delicate structures, as well as supplying important
nutrients for brain cells. CSF is reabsorbed by blood
vessels located within the meninges. A careful balance
between CSF production and reabsorption is important to avoid the accumulation of too much CSF.
Because the brain is enclosed in the hard, bony
case of the skull, any disease that produces swelling
2397

Meningitis

H A T T I E A L E X A N D E R (1901–1968)
became one of the first women to head a national medical
association.
As an intern at the Harriet Lane Home of Johns
Hopkins Hospital from 1930 to 1931, Alexander became
interested in influenzal meningitis. The source of the disease was Hemophilus influenzae, a bacteria that causes
inflammation of the meninges, the membranes surrounding the brain and spinal cord. In 1931, Alexander began a
second internship at the Babies Hospital of the ColumbiaPresbyterian Medical Center in New York City. There, she
witnessed first-hand the futility of medical efforts to save
babies who had contracted influenzal meningitis.

(Betmann/CORBIS. Reproduced by permission.)

Hattie Alexander, a dedicated pediatrician, medical
educator, and researcher in microbiology, won international recognition for deriving a serum to combat influenzal meningitis, a common disease that previously had been
nearly always fatal to infants and young children.
Alexander subsequently investigated microbiological
genetics and the processes whereby bacteria, through
genetic mutation, acquire resistance to antibiotics. In
1964, as president of the American Pediatric Society, she

will be damaging to the brain. The skull cannot
expand at all, so when the swollen brain tissue pushes
up against the skull’s hard bone, the brain tissue
becomes damaged and may ultimately die.
Furthermore, swelling on the right side of the brain
will not only cause pressure and damage to that side of
the brain, but by taking up precious space within the
tight confines of the skull, the left side of the brain will
also be pushed up against the hard surface of the skull,
causing damage to the left side of the brain as well.
Another way that infections injure the brain
involves the way in which the chemical environment of
the brain changes in response to the presence of an
infection. The cells of the brain require a very wellregulated environment. Careful balance of oxygen,
carbon dioxide, sugar (glucose), sodium, calcium, potassium, and other substances must be maintained in order
2398

Alexander’s early research focused on deriving a
serum (the liquid component of blood, in which antibodies
are contained) that would be effective against influenzal
meningitis. Serums derived from animals that have been
exposed to a specific disease-producing bacterium often
contain antibodies against the disease and can be developed for use in immunizing humans against it. Alexander
knew that the Rockefeller Institute in New York City, however, had been able to prepare a rabbit serum for the
treatment of pneumonia, another bacterial disease.
Alexander therefore experimented with rabbit serums,
and by 1939 was able to announce the development of a
rabbit serum effective in curing infants of influenzal
meningitis.
In the early 1940s, Alexander experimented with the
use of drugs in combination with rabbit serum in the treatment of influenzal meningitis. Within the next two years,
she saw infant deaths due to the disease drop by eighty
percent.

to avoid damage to brain tissue. An infection upsets this
balance, and brain damage can occur when the cells of
the brain are either deprived of important nutrients or
exposed to toxic levels of particular substances.
The cells lining the brain’s tiny blood vessels
(capillaries) are specifically designed to prevent many
substances from passing into brain tissue. This is commonly referred to as the blood-brain barrier. The
blood-brain barrier prevents various substances that
could be poisonous to brain tissue (toxins), as well as
many agents of infection, from crossing from the
blood stream into the brain tissue. While this barrier
is obviously an important protective feature for the
brain, it also serves to complicate treatment in the case
of an infection by making it difficult for medications
to pass out of the blood and into the brain tissue where
the infection is located.
GALE ENCYCLOPEDIA OF MEDICINE

The most common infectious causes of meningitis
vary according to an individual’s age, habits, living
environment, and health status. While nonbacterial
types of meningitis are more common, bacterial
meningitis is the more potentially life-threatening.
Three bacterial agents are responsible for about 80%
of all bacterial meningitis cases. These bacteria are
Haemophilus influenzae type b, Neisseria meningitidis
(causing meningococcal meningitis), and Streptococcus
pneumoniae (causing pneumococcal meningitis).
In newborns, the most common agents of meningitis are those that are contracted from the newborn’s
mother, including Group B streptococci (becoming an
increasingly common infecting organism in the newborn period), Escherichia coli, and Listeria monocytogenes. The highest incidence of meningitis occurs in
babies under a month old, with an increased risk of
meningitis continuing through about two years of age.
Older children are more frequently infected by the
bacteria Haemophilus influenzae, Neisseria meningitidis, and Streptococci pneumoniae.
Adults are most commonly infected by either S.
pneumoniae or N. meningitidis, with pneumococcal
meningitis the more common. Certain conditions predispose to this type of meningitis, including alcoholism
and chronic upper respiratory tract infections (especially of the middle ear, sinuses, and mastoids).
N. meningitidis is the only organism that can cause
epidemics of meningitis. In particular, these have
occurred when a child in a crowded day-care situation
or a military recruit in a crowded training camp has
fallen ill with meningococcal meningitis.
Viral causes of meningitis include the herpes simplex virus, the mumps and measles viruses (against
which most children are protected due to mass immunization programs), the virus that causes chicken pox,
the rabies virus, and a number of viruses that are
acquired through the bites of infected mosquitoes.
A number of medical conditions predispose individuals to meningitis caused by specific organisms.
Patients with AIDS (acquired immune deficiency syndrome) are more prone to getting meningitis from
fungi, as well as from the agent that causes tuberculosis. Patients who have had their spleens removed, or
whose spleens are no longer functional (as in the case
of patients with sickle cell disease) are more susceptible
to other infections, including meningococcal and
pneumococcal meningitis.
The majority of meningitis infections are acquired
by blood-borne spread. A person may have another
GALE ENCYCLOPEDIA OF MEDICINE

type of infection (of the lungs, throat, or tissues of the
heart) caused by an organism that can also cause
meningitis. If this initial infection is not properly treated, the organism will continue to multiply, find its
way into the blood stream, and be delivered in sufficient quantities to invade past the blood brain barrier.
Direct spread occurs when an organism spreads to the
meninges from infected tissue next to or very near the
meninges. This can occur, for example, with a severe,
poorly treated ear or sinus infection.
Patients who suffer from skull fractures possess
abnormal openings to the sinuses, nasal passages, and
middle ears. Organisms that usually live in the human
respiratory system without causing disease can pass
through openings caused by such fractures, reach the
meninges, and cause infection. Similarly, patients who
undergo surgical procedures or who have had foreign
bodies surgically placed within their skulls (such as
tubes to drain abnormal amounts of accumulated
CSF) have an increased risk of meningitis.
Organisms can also reach the meninges via an
uncommon but interesting method called intraneural
spread. This involves an organism invading the body
at a considerable distance away from the head,
spreading along a nerve, and using that nerve as a
kind of ladder into the skull, where the organism can
multiply and cause meningitis. Herpes simplex virus
is known to use this type of spread, as is the rabies
virus.
The most classic symptoms of meningitis (particularly of bacterial meningitis) include fever, headache,
vomiting, sensitivity to light (photophobia), irritability, severe fatigue (lethargy), stiff neck, and a reddish
purple rash on the skin. Untreated, the disease progresses with seizures, confusion, and eventually coma.
A very young infant may not show the classic
signs of meningitis. Early in infancy, a baby’s immune
system is not yet developed enough to mount a fever in
response to infection, so fever may be absent. Some
infants with meningitis have seizures as their only
identifiable symptom. Similarly, debilitated elderly
patients may not have fever or other identifiable symptoms of meningitis.
Damage due to meningitis occurs from a variety
of phenomena. The action of infectious agents on the
brain tissue is one direct cause of damage. Other types
of damage may be due to the mechanical effects of
swelling and compression of brain tissue against the
bony surface of the skull. Swelling of the meninges
may interfere with the normal absorption of CSF by
blood vessels, causing accumulation of CSF and
damage from the resulting pressure on the brain.
2399

Meningitis

Causes and symptoms

Meningitis

Interference with the brain’s carefully regulated chemical environment may cause damaging amounts of
normally present substances (carbon dioxide, potassium) to accumulate. Inflammation may cause the
blood-brain barrier to become less effective at preventing the passage of toxic substances into brain tissue.

Diagnosis
A number of techniques are used when examining
a patient suspected of having meningitis to verify the
diagnosis. Certain manipulations of the head (lowering the head, chin towards chest, for example) are
difficult to perform and painful for a patient with
meningitis.
The most important test used to diagnose meningitis is the lumbar puncture (commonly called a spinal
tap). Lumbar puncture (LP) involves the insertion of a
thin needle into a space between the vertebrae in the
lower back and the withdrawal of a small amount of
CSF. The CSF is then examined under a microscope to
look for bacteria or fungi. Normal CSF contains set
percentages of glucose and protein. These percentages
will vary with bacterial, viral, or other causes of
meningitis. For example, bacterial meningitis causes
a greatly lower than normal percentage of glucose to
be present in CSF, as the bacteria are essentially
‘‘eating’’ the host’s glucose, and using it for their
own nutrition and energy production. Normal CSF
should contain no infection-fighting cells (white
blood cells), so the presence of white blood cells in
CSF is another indication of meningitis. Some of the
withdrawn CSF is also put into special lab dishes to
allow growth of the infecting organism, which can
then be identified more easily. Special immunologic
and serologic tests may also be used to help identify
the infectious agent.
In rare instances, CSF from a lumbar puncture
cannot be examined because the amount of swelling
within the skull is so great that the pressure within the
skull (intracranial pressure) is extremely high. This
pressure is always measured immediately upon insertion of the LP needle. If it is found to be very high, no
fluid is withdrawn because doing so could cause herniation of the brain stem. Herniation of the brain stem
occurs when the part of the brain connecting to the
spinal cord is thrust through the opening at the base of
the skull into the spinal canal. Such herniation will
cause compression of those structures within the brain
stem that control the most vital functions of the body
(breathing, heart beat, consciousness). Death or permanent debilitation follows herniation of the brain
stem.
2400

KEY TERMS
Blood-brain barrier—An arrangement of cells
within the blood vessels of the brain that prevents
the passage of toxic substances, including infectious agents, from the blood and into the brain. It
also makes it difficult for certain medications to
pass into brain tissue.
Cerebrospinal fluid (CSF)—Fluid made in chambers
within the brain which then flows over the surface of
the brain and spinal cord. CSF provides nutrition to
cells of the nervous system, as well as providing a
cushion for the nervous system structures. It may
accumulate abnormally in some disease processes,
causing pressure on and damage to brain structures.
Lumbar puncture (LP)—A medical test in which a
very narrow needle is inserted into a specific space
between the vertebrae of the lower back in order to
draw off a sample of CSF for further examination.
Meninges—The three-layer membranous covering
of the brain and spinal cord, composed of the dura,
arachnoid, and pia. It provides protection for the
brain and spinal cord, as well as housing many
blood vessels and participating in the appropriate
flow of CSF.

Treatment
Antibiotic medications (forms of penicillin and
cephalosporins, for example) are the most important
element of treatment against bacterial agents of
meningitis. Because of the effectiveness of the bloodbrain barrier in preventing the passage of substances
into the brain, medications must be delivered directly
into the patient’s veins (intravenously, or by IV), at
very high doses. Antiviral drugs (acyclovir) may be
helpful in shortening the course of viral meningitis,
and antifungal medications are available as well.
Other treatments for meningitis involve decreasing inflammation (with steroid preparations) and paying careful attention to the balance of fluids, glucose,
sodium, potassium, oxygen, and carbon dioxide in the
patient’s system. Patients who develop seizures will
require medications to halt the seizures and prevent
their return.

Prognosis
Viral meningitis is the least severe type of meningitis, and patients usually recover with no long-term
effects from the infection. Bacterial infections,
GALE ENCYCLOPEDIA OF MEDICINE

formally called Neisseria meningitidis, can be one of
the most dramatic and rapidly fatal of all infectious
diseases.

The most frequent long-term effects of meningitis
include deafness and blindness, which may be caused
by the compression of specific nerves and brain areas
responsible for the senses of hearing and sight. Some
patients develop permanent seizure disorders, requiring life-long treatment with anti-seizure medications.
Scarring of the meninges may result in obstruction of
the normal flow of CSF, causing abnormal accumulation of CSF. This may be a chronic problem for some
patients, requiring the installation of shunt tubes to
drain the accumulation regularly.

Meningococcemia, a relatively uncommon infection, occurs most commonly in children and young
adults. In susceptible people, it may cause a very severe
illness that can produce death within hours. The bacteria, which can spread from person to person, usually
first causes a colonization in the upper airway, but
without symptoms. From there, it can penetrate into
the bloodstream to the central nervous system and
cause meningitis or develop into a full-blown bloodstream infection (meningococcemia). Fortunately in
most colonized people, this does not happen and the
result of this colonization is long-lasting immunity
against the particular strain.

Prevention
Prevention of meningitis primarily involves the
appropriate treatment of other infections an individual
may acquire, particularly those that have a track record
of seeding to the meninges (such as ear and sinus infections). Preventive treatment with antibiotics is sometimes recommended for the close contacts of an
individual who is ill with meningococcal or H. influenzae type b meningitis. A meningococcal vaccine exists,
and is sometimes recommended to individuals who
are traveling to very high risk areas. A vaccine for
H. influenzae type b is now given to babies as part of
the standard array of childhood immunizations.
Resources
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave.,
St. Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.
Meningitis Foundation of America. 7155 Shadeland
Station, Suite 190, Indianapolis, IN 46256-3922. (800)
668-1129. <http://www.musa.org/welcome.htm>.

Rosalyn Carson-DeWitt, MD

Meningocele see Spina bifida

Meningococcemia
Definition
Meningococcemia is the presence of meningococcus in the bloodstream. Meningococcus, a bacteria
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms

After colonization is established, symptoms can
develop within one day to one to two weeks. After a
short period of time (one hour up to one to two days)
when the patient complains of fever and muscle aches,
more severe symptoms can develop. Unfortunately
during this early stage, a doctor cannot tell this illness
from any other illness, such as a viral infection like
influenza. Unless the case is occurring in a person
known to have been exposed to or in the midst of an
epidemic of meningococcal disease, there may be no
specific symptoms or signs found that help the doctor
diagnose the problem. Rarely, a low-grade bloodstream infection called chronic meningococcemia can
occur.
After this initial period, the patient will often
complain of continued fever, shaking chills, overwhelming weakness, and even a feeling of impending
doom. The organism is multiplying in the bloodstream, unchecked by the immune system. The severity of the illness and its dire complications are caused
by the damage the organism does to the small blood
vessel walls. This damage is called a vasculitis, an
inflammation of a blood vessel. Damage to the small
vessels causes them to become leaky. The first signs of
the infection’s severity are small bleeding spots seen on
the skin (petechiae). A doctor should always suspect
meningococcemia when he/she finds an acutely ill
patient with fever, chills, and petechiae.
Quickly (within hours), the blood vessel damage
increases and large bleeding areas on the skin
(purpura) are seen. The same changes are taking
place in the affected person’s internal organs. The
blood pressure is often low and there may be signs
of bleeding from other organs (like coughing up
2401

Meningococcemia

however, are much more severe, and progress rapidly.
Without very rapid treatment with the appropriate
antibiotic, the infection can swiftly lead to coma and
death in less than a day’s time. While death rates from
meningitis vary depending on the specific infecting
organism, the overall death rate is just under 20%.

Meningococcemia

KEY TERMS
Blood culture—A procedure where blood is collected from a vein and is placed in a small bottle
that contains a special liquid; the liquid will make
any organisms that are present in the blood sample
grow. These organisms can then be grown and
identified in the laboratory so that the proper antibiotic can be given to the patient.

A close-up image of a person’s hand with meningococcemia.
This disease is caused by the presence of meningococcus
(Neisseria meningitidis) in the bloodstream. The organism
can cause multiple illnesses and can damage small blood
vessels. (Custom Medical Stock Photo. Reproduced by
permission.)

blood, nose bleeds, blood in the urine). The organism
not only damages the blood vessels by causing them
to leak, but also causes clotting inside the vessels.
If this clotting occurs in the larger arteries, it results
in major tissue damage. Essentially, large areas of
skin, muscle, and internal organs die from lack of
blood and oxygen. Even if the disease is quickly
diagnosed and treated, the patient has a high risk of
dying.

Diagnosis
The diagnosis of meningococcemia can be made
by the growth of the organism from blood cultures.
Treatment should begin when the diagnosis is suspected and should not be delayed waiting for positive
cultures. Obtaining fluid from a petechial spot and
staining it in the laboratory can assist in quickly seeing
the organism.

Treatment
Immediate treatment of a suspected case of
meningococcemia begins with antibiotics that work
against the organism. Possible choices include penicillin G, ceftriaxone (Rocephin), cefotaxime (Claforan),
or trimethoprim/sulfamethoxazole (Bactrim, Septra).
If the patient is diagnosed in a doctor’s office, antibiotics should be given immediately if possible, even
before transfer to the hospital and even if cultures
cannot be obtained before treatment. It is most likely
that the speed of initial treatment will affect the ultimate outcome.
2402

Colonization—The presence of bacteria on a body
surface (like on the skin, mouth, intestines or airway) without causing disease in the person.
Complement—One of several proteins in the blood
that acts with other proteins to assist in killing
bacteria.
Meningitis—Inflammation of the membranes of the
brain or spinal cord.

Prognosis
As many as 15-20% of patients with meningococcemia will die as a result of the acute infection. A
significant percentage of the survivors will have tissue
damage that requires surgical treatment. This treatment may consist of skin grafts, or even partial or full
amputations of an arm or leg. Certain people with
immune system defects (particularly those with defects
in the complement system) may have recurrent episodes of meningococcemia. These patients, however,
seem to have a less serious outcome.

Prevention
Although a vaccine is available for meningococcus, it is still difficult at this time to produce a vaccine
for the type B organism, the most common one in the
United States. Because of this and the short time that
the vaccine seems to offer protection, the product has
not been routinely used in the United States. It can be
used for travelers going to areas where meningococcal
disease is more common or is epidemic. Recently, the
vaccine has been suggested for use in incoming college
freshman, particularly those living in dormitories.
These students appear to have a somewhat higher
risk of meningococcal infections.
It is, however, recommended that all people take
certain antibiotics if they have had contact (like at
home or in a daycare) with a person who has meningococcal infection. The most common antibiotics
given are rifampin (Rifadin) or ciprofloxacin (Cipro).
These medicines are usually taken by mouth twice a
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

Salzman, Mark B., and Lorry G. Rubin.
‘‘Meningococcemia.’’ Infectious Disease Clinics of
North America 10 (December 1996): 709-725.

Larry I. Lutwick, MD

Meningomyelocele see Spina bifida
Menkes’ syndrome see Mineral deficiency

Menopause
Definition
Menopause represents the end of menstruation.
While technically it refers to the final period, it is not
an abrupt event, but a gradual process. Menopause is
not a disease that needs to be cured, but a natural lifestage transition. However, women have to make
important decisions about ‘‘treatment,’’ including the
use of hormone replacement therapy (HRT).

Description
Many women have irregular periods and other
problems of ‘‘pre-menopause’’ for years. It is not
easy to predict when menopause begins, although
doctors agree it is complete when a woman has not
had a period for a year. Eight out of every 100 women
stop menstruating before age 40. At the other end of
the spectrum, five out of every 100 continue to have
periods until they are almost 60. The average age of
menopause is 51.
There is no mathematical formula to figure out
when the ovaries will begin to scale back either, but a
woman can get a general idea based on her family
history, body type, and lifestyle. Women who began
menstruating early will not necessarily stop having
periods early as well. It is true that a woman will likely
enter menopause at about the same age as her mother.
Menopause may occur later than average among
smokers.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Once a woman enters puberty, each month her
body releases one of the more than 400,000 eggs that
are stored in her ovaries, and the lining of the womb
(uterus) thickens in anticipation of receiving a fertilized egg. If the egg is not fertilized, progesterone levels
drop and the uterine lining sheds and bleeds.
By the time a woman reaches her late 30s or 40s,
her ovaries begin to shut down, producing less estrogen and progesterone and releasing eggs less often.
The gradual decline of estrogen causes a wide variety
of changes in tissues that respond to estrogen—including the vagina, vulva, uterus, bladder, urethra, breasts,
bones, heart, blood vessels, brain, skin, hair, and
mucous membranes. Over the long run, the lack of
estrogen can make a woman more vulnerable to osteoporosis (which can begin in the 40s) and heart disease.
As the levels of hormones fluctuate, the menstrual
cycle begins to change. Some women may have longer
periods with heavy flow followed by shorter cycles and
hardly any bleeding. Others will begin to miss periods
completely. During this time, a woman also becomes
less able to get pregnant.
The most common symptom of menopause is a
change in the menstrual cycle, but there are a variety of
other symptoms as well, including:


hot flashes



night sweats



insomnia



mood swings/irritability



memory or concentration problems



vaginal dryness



heavy bleeding



fatigue



depression



hair changes



headaches



heart palpitations



sexual disinterest



urinary changes



weight gain

Diagnosis
The clearest indication of menopause is the
absence of a period for one year. It is also possible to
diagnose menopause by testing hormone levels. One
2403

Menopause

day for two days. This treatment will decrease the risk
of infection in these people who have been exposed.
However, the overall risk to people who have been
exposed, even without antibiotic use, is probably no
more than 1-2%.

Menopause

important test measures the levels of follicle-stimulating hormone (FSH), which steadily increases as a
woman ages.
However, as a woman first enters menopause, her
hormones often fluctuate wildly from day to day. For
example, if a woman’s estrogen levels are high and
progesterone is low, she may have mood swings, irritability, and other symptoms similar to premenstrual
syndrome (PMS). As hormone levels shift and estrogen
level falls, hot flashes occur. Because of these fluctuations, a normal hormone level when the blood is tested
may not necessarily mean the levels were normal the
day before or will be the day after.
If it has been at least three months since a woman’s
last period, an FSH test might be more helpful in
determining whether menopause has occurred. Most
doctors believe that the FSH test alone cannot be used
as proof that a woman has entered early menopause.
A better measure of menopause is a test that checks the
levels of estrogen, progesterone, testosterone and other
hormones at mid-cycle, in addition to FSH.

Treatment
When a woman enters menopause, her levels of
estrogen drop and symptoms (such as hot flashes and
vaginal dryness) begin. Hormone replacement therapy
can treat these symptoms by boosting the estrogen
levels enough to suppress symptoms while also providing protection against heart disease and osteoporosis,
which causes the bones to weaken. Experts disagree on
whether HRT increases or decreases the risk of developing breast cancer. A Harvard study concluded that
short-term use of hormones carries little risk, while
HRT used for more than five years among women 55
and over seems to increase the risk of breast cancer.
There are two types of hormone treatments: hormone replacement therapy (HRT) and estrogen replacement therapy (ERT). HRT is the administration of
estrogen and progesterone; ERT is the administration
of estrogen alone. Only women who have had a hysterectomy (removal of the uterus) can take estrogen
alone, since taking this ‘‘unopposed’’ estrogen can
cause uterine cancer. The combination of progesterone and estrogen in HRT eliminates the risk of uterine
cancer.
Most physicians do not recommend HRT until a
woman’s periods have stopped completely for one
year. This is because women in early menopause who
still have an occasional period are still producing
estrogen; HRT would then provide far too much
estrogen.
2404

Most doctors believe that every woman (except
those with certain cancers) should take hormones as
they approach menopause because of the protection
against heart disease, osteoporosis, and uterine cancer
and the relatively low risk of breast cancer. Heart
disease and osteoporosis are two of the leading causes
of disability and death among post-menopausal
women.
Critics say the benefit of taking hormonal drugs to
ease symptoms is not worth the risk of breast cancer.
Since menopause is not a disease, many argue that
women should not take hormones to cure what is actually a natural process of aging. Advocates of HRT
contend that the purpose of taking hormones is not to
‘‘treat’’ menopause but to prevent the development
of other diseases.
There are risks with HRT and there are risks without it. In order to decide whether to take HRT, a
woman should balance her risk of getting breast cancer against her risk of getting heart disease, and decide
how bad her menopause symptoms are. Most doctors
agree that short-term use of estrogen for those women
with symptoms of hot flashes or night sweats is a
sensible choice as long as they do not have a history
of breast cancer.
For a woman who has no family history of cancer
and a high risk of dying from heart disease, for example, the low risk of cancer might be worth the protective benefit of avoiding heart disease. Certainly, for
Caucasian women aged 50 to 94, the risk of dying from
heart disease is far greater than the risk of dying of
breast cancer.
Women are poor candidates for hormone replacement therapy if they have:


had breast or endometrial cancer



a close relative (mother, sister, grandmother) who
died of breast cancer or have two relatives who developed breast cancer before age 40



had endometrial cancer



had gallbladder or liver disease



blood clots or phlebitis

Some women with liver or gallbladder disease, or
who have clotting problems, may be able to go on
HRT if they use a patch to administer the hormones
through the skin, bypassing the liver.
Women would make a good candidate for HRT if
they:


need to prevent osteoporosis



have had their ovaries removed
GALE ENCYCLOPEDIA OF MEDICINE

need to prevent heart disease



have significant symptoms.

Taking hormones can almost immediately eliminate hot flashes, vaginal dryness, urinary incontinence
(depending on the cause), insomnia, moodiness, memory problems, heavy irregular periods, and concentration problems. Side effects of treatment include
bloating, breakthrough bleeding, headaches, vaginal
discharge, fluid retention, swollen breasts, or nausea.
Up to 20% of women who try hormone replacement
stop within nine months because of these side effects.
However, some side effects can be lessened or prevented by changing the HRT regimen.
The decision should be made by a woman and her
doctor after taking into consideration her medical
history and situation. Women who choose to take
hormones should have an annual mammogram, breast
exam, and pelvic exam and should report any unusual
vaginal bleeding or spotting (a sign of possible uterine
cancer).
Anti-estrogens
A new type of hormone therapy offers some of the
same protection against heart disease and bone loss as
estrogen, but without the increased risk of breast
cancer. This new class of drugs are known as antiestrogens. The best known of these anti-estrogens is
raloxifene, which mimics the effects of estrogen in the
bones and blood, but blocks some of its negative
effects elsewhere. It is called an anti-estrogen because
for a long time these drugs had been used to counter
the harmful effects of estrogen that caused breast cancer. Oddly enough, in other parts of the body these
drugs mimic estrogen, protecting against heart disease
and osteoporosis without putting a woman at risk for
breast cancer.
Like estrogen, raloxifene works by attaching to an
estrogen ‘‘receptor,’’ much like a key fits into a lock.
When raloxifene clicks into the estrogen receptors in
the breast and uterus, it blocks estrogen at these sites.
This is the secret of its cancer-fighting property. Many
tumors in the breast are fueled by estrogen; if the
estrogen cannot get in the cell, then the cancer stops
growing.
Women may prefer to take raloxifene instead of
hormone replacement because the new drug does not
boost the breast cancer risk and does not have side
effects like uterine bleeding, bloating, or breast soreness. Unfortunately, the drug may worsen hot flashes.
Raloxifene is basically a treatment to prevent osteoporosis. It does not help with common symptoms and
GALE ENCYCLOPEDIA OF MEDICINE

it is unclear if it has the same protective effect against
heart disease as estrogen does.
Testosterone replacement
The ovaries also produce a small amount of male
hormones, which decreases slightly as a woman enters
menopause. The vast majority of women never need
testosterone replacement, but it can be important if a
woman has declining interest in sex. Testosterone can
improve the libido, and decrease anxiety and depression; adding testosterone especially helps women who
have had hysterectomies. Testosterone also eases
breast tenderness and helps prevent bone loss.
However, testosterone does have side effects. Some
women experience mild acne and some facial hair
growth, but because only small amounts of testosterone are prescribed, most women do not appear to have
extreme masculine changes.
Birth control pills
Women who are still having periods but who have
annoying menopausal symptoms may take low-dose
birth control pills to ease the problems; this treatment
has been approved by the FDA for perimenopausal
symptoms in women under age 55. HRT is the preferred treatment for menopause, however, because it
uses lower doses of estrogen.

Alternative treatment
Some women also report success in using natural
remedies to treat the unpleasant symptoms of menopause. Not all women need estrogen and some women
cannot take it. Many doctors don’t want to give hormones to women who are still having their periods,
however erratically. Indeed, only a third of menopausal women in the United States try HRT and of those
who do, eventually half of them drop the therapy.
Some are worried about breast cancer, some cannot
tolerate the side effects, some do not want to medicate
what they consider to be a natural occurrence.
Herbs
Herbs have been used to relieve menopausal
symptoms for centuries. In general, most herbs are
considered safe, and there is no substantial evidence
that herbal products are a major source of toxic reactions. But because herbal products are not regulated in
the United States, contamination or accidental overdose is possible. Herbs should be bought from a recognized company or through a qualified herbal
practitioner.
2405

Menopause



Menopause

Women who choose to take herbs for menopausal
symptoms should learn as much as possible about
herbs and work with a qualified practitioner (an herbalist, a traditional Chinese doctor, or a naturopathic
physician). Pregnant women should avoid herbs
because of unknown effects on a developing fetus.
The following list of herbs include those that herbalists most often prescribe to treat menstrual
complaints:


Black cohosh (Cimicifuga racemosa): hot flashes and
other menstrual complaints



Black currant: breast tenderness



Chaste tree/chasteberry (Vitex agnus-castus): hot
flashes, excessive menstrual bleeding, fibroids, and
moodiness



Evening primrose oil (Oenothera biennis): mood
swings, irritability, and breast tenderness



Fennel (Foeniculum vulgare): hot flashes, digestive
gas, and bloating



Flaxseed (linseed): excessive menstrual bleeding,
breast tenderness, and other symptoms, including
dry skin and vaginal dryness



Gingko (Gingko biloba): memory problems



Ginseng (Panax ginseng): hot flashes, fatigue and
vaginal thinning.



Hawthorn (Crataegus laevigata): memory problems,
fuzzy thinking



Lady’s mantle: excessive menstrual bleeding



Mexican wild yam (Dioscorea villosa) root: vaginal
dryness, hot flashes and general menopause
symptoms



Motherwort (Leonurus cardiaca): night sweats, hot
flashes



Oat (Avena sativa) straw: mood swings, anxiety



Red clover (Trifolium pratense): hot flashes



Sage (Salvia officinalis): mood swings, headaches,
night sweats



Valerian (Valeriana officinalis): insomnia.
Natural estrogens (phytoestrogens)

Proponents of plant estrogens (including soy products) believe that plant estrogens are better than
synthetic estrogen, but science has not yet proven
this. The results of smaller preliminary trials suggest
that the estrogen compounds in soy products can
indeed relieve the severity of hot flashes and lower
cholesterol. But no one yet has proven that soy can
2406

provide all the benefits of synthetic estrogen without
its negative effects.
It is true that people in other countries who eat
foods high in plant estrogens (especially soy products)
have lower rates of breast cancer and report fewer
‘‘symptoms’’ of menopause. While up to 80% of menopausal women in the United States complain of hot
flashes, night sweats, and vaginal dryness, only 15%
of Japanese women have similar complaints. When all
other things are equal, a soy-based diet may make a
difference (and soy is very high in plant estrogens).
The study of phytoestrogens is so new that there
are not very many recommendations on how much a
woman can consume. Herbal practitioners recommend a dose based on a woman’s history, body size,
lifestyle, diet, and reported symptoms. Research has
indicated that some women were able to ease their
symptoms by eating a large amount of fruits, vegetables, and whole grains, together with four ounces of
tofu four times a week.
What concerns some critics of other alternative
remedies is that many women think that ‘‘natural’’ or
‘‘plant-based’’ means ‘‘harmless.’’ In large doses, phytoestrogens can promote the abnormal growth of cells
in the uterine lining. Unopposed estrogen of any type
can lead to endometrial cancer, which is why women
on conventional estrogen-replacement therapy usually
take progesterone (progestin) along with their estrogen. However, a plant-based progesterone product
can sometimes be effective alone, without estrogen,
in assisting the menopausal woman in rebalancing
her hormonal action throughout this transition time.
Yoga
Many women find that yoga (the ancient meditation/exercise developed in India 5,000 years ago) can ease
menopausal symptoms. Yoga focuses on helping women
unite the mind, body, and spirit to create balance.
Because yoga has been shown to balance the endocrine
system, some experts believe it may affect hormonerelated problems. Studies have found that yoga can
reduce stress, improve mood, boost a sluggish metabolism, and slow the heart rate. Specific yoga positions deal
with particular problems, such as hot flashes, mood
swings, vaginal and urinary problems, and other pains.
Exercise
Exercise helps ease hot flashes by lowering the
amount of circulating FSH and LH and by raising
endorphin levels that drop while having a hot flash.
Even exercising 20 minutes three times a week can
significantly reduce hot flashes.
GALE ENCYCLOPEDIA OF MEDICINE

Menopause

KEY TERMS
Endometrium—The lining of the uterus that is shed
with each menstrual period.
Estrogen—Female hormone produced by the ovaries
and released by the follicles as they mature.
Responsible for female sexual characteristics, estrogen stimulates and triggers a response from at least
300 tissues, and may help some types of breast cancer to grow. After menopause, the production of the
hormone gradually stops.
Estrogen replacement therapy (ERT)—A treatment
for menopause in which estrogen is given in pill,
patch, or cream form.
Follicle-stimulating hormone (FSH)—The pituitary
hormone that stimulates the ovary to mature egg
capsules (follicles). It is linked with rising estrogen
production throughout the cycle. An elevated FSH
(above 40) indicates menopause.

Hysterectomy—Surgical removal of the uterus.
Ovary—One of the two almond-shaped glands in
the female reproductive system responsible for producing eggs and the hormones estrogen and
progesterone.
Ovulation—The monthly release of an egg from the
ovary.
Pituitary gland—The ‘‘master gland’’ at the base of
the brain that secretes a number of hormones responsible for growth, reproduction, and other activities.
Pituitary hormones stimulate the ovaries to release
estrogen and progesterone.
Progesterone—The hormone that is produced by the
ovary after ovulation to prepare the uterine lining for
a fertilized egg.

Hormone—A chemical messenger secreted by a
gland that is released into the blood, and that travels
to distant cells where it exerts an effect.

Testosterone—Male hormone produced by the
testes and (in small amounts) in the ovaries.
Testosterone is responsible for some masculine secondary sex characteristics such as growth of body
hair and deepening voice.

Hormone replacement therapy (HRT)—The use of
estrogen and progesterone to replace hormones that
the ovary no longer supplies.

Uterus—The female reproductive organ that contains and nourishes a fetus from implantation until
birth. Also known as the womb.

Hot flash—A wave of heat that is one of the most
common perimenopausal symptoms, triggered by
the hypothalamus’ response to estrogen withdrawal.

Vagina—The tube-like passage from the vulva (a
woman’s external genital structures) to the cervix
(the portion of the uterus that projects into the vagina).

Elimination
Regular, daily bowel movements to eliminate
waste products from the body can be crucial in maintaining balance through menopause. The bowels are
where circulating hormones are gathered and eliminated, keeping the body from recycling them and
causing an imbalance.
Acupuncture
This ancient Asian art involves placing very thin
needles into different parts of the body to stimulate the
system and unblock energy. It is usually painless and
has been used for many menopausal symptoms,
including insomnia, hot flashes, and irregular periods.
Practitioners believe that acupuncture can facilitate the
opening of blocked energy channels, allowing the life
force energy (chi) to flow freely. This allows the menopausal woman to keep her energy moving. Blocked
energy usually increases the symptoms of menopause.
GALE ENCYCLOPEDIA OF MEDICINE

Acupressure and massage
Therapeutic massage involving acupressure can
bring relief from a wide range of menopause symptoms by placing finger pressure at the same meridian
points on the body that are used in acupuncture.
There are more than 80 different types of massage,
including foot reflexology, Shiatsu massage, or
Swedish massage, but they are all based on the idea
that boosting the circulation of blood and lymph
benefits health.
Biofeedback
Some women have been able to control hot flashes
through biofeedback, a painless technique that helps a
person train her mind to control her body. A biofeedback machine provides information about body processes (such as heart rate) as the woman relaxes her
body. Using this technique, it is possible to control the
body’s temperature, heart rate, and breathing.
2407

Men’s health

Prognosis
Menopause is a natural condition of aging. Some
women have no problems at all with menopause, while
others notice significant unpleasant symptoms. A wide
array of treatments, from natural to hormone replacement, mean that no woman needs to suffer through
this time of her life.

Prevention
Menopause is a natural part of the aging process
and not a disease that needs to be prevented. Most
doctors recommend HRT for almost all post-menopausal women, usually for a few years. When HRT is
then stopped, symptoms should be mild or non existent. But HRT is not only useful in lessening the
symptoms of menopause; it also protects against
heart disease and osteoporosis.
Resources
BOOKS

Goldman, Lee, et al., editors. Cecil Textbook of Medicine.
21st ed. W. B. Saunders, 2000.
Goroll, Allan H., et al. Primary Care Medicine. 4th ed.
Lippincott Williams &Wilkins, 2000.
OTHER

Menopause Online Page. <http://www.menopause-online
.com/links.htm>.
Menopause Page. <http://www.howdyneighbor.com/
menopaus>.
Meno Times Online. <http://www.aimnet.com/hyperion/
meno/menotimes.index.html>.

Laith Farid Gulli, M.D.

Menorrhagia see Dysfunctional uterine
bleeding

discrepancy are not completely understood. Men
may have some genetic predisposition for lower life
expectancy, as women tend to outlive men in most
areas throughout the world. But men also have different lifestyle patterns that increase the wear and tear on
their bodies. Studies have shown that men tend to
drink and smoke more than women, men obtain medical care less frequently than women, and men generally have more stressful habits. It is clear to health
professionals that men can benefit from increased
knowledge of male medical issues and by understanding how lifestyle choices impact health.
According to the Centers for Disease Control
(CDC), the 10 leading causes of death for men in the
United States are:


heart disease



cancer



stroke



accidents



lung disease (including emphysema and chronic
bronchitis)



pneumonia



diabetes



suicide



liver disease



homicides

Men also suffer regularly from conditions as
diverse as sexually transmitted diseases (STDs), mental
illness, arthritis, urinary tract infections, athletic injuries, hair and skin problems, and digestive disorders.
The field of men’s health strives to reduce the risks and
incidence of men’s conditions by researching preventive practices, designing testing procedures for early
detection, and recommending specialized courses of
treatment.

Description

Men’s health
Definition
Men’s health is concerned with identifying, preventing, and treating conditions that are most common or specific to men.

Purpose
Men live on average seven years less than women;
life expectancy in the United States is 72 years for men
and 79 years for women. The reasons for this
2408

Prevention
Preventive practices for men’s health emphasize
diet, exercise and stress management, as well as the
elimination of risky behaviors such as smoking and
excessive drinking. Four of the leading causes of
death for American men are related to diet—heart
disease, cancer, stroke, and diabetes. In addition men
are more likely than women to suffer from diet-related
conditions including high cholesterol, high blood pressure, and obesity, all of which increase the risk of
certain diseases and premature death.
GALE ENCYCLOPEDIA OF MEDICINE

Exercise
The health of men has been affected as work
patterns have shifted. Physical labor has been replaced
by machines and office work. Studies have estimated
that more than 30% of Americans are now obese,
which means that nearly one out of three people is
significantly overweight. Obesity poses many risks
including increased chance of heart disease, diabetes,
and some cancers. Effective exercise programs help
men control weight, reduce stress, increase energy
levels, improve self-esteem, reduce pain and injuries,
and improve sleep. Exercise programs should emphasize flexibility and stretching as well as plenty of aerobic activities, such as running and swimming. These
activities exercise the heart and lungs and burn excess
calories. Men may also choose anaerobic activities
such as weight training to add muscles and increase
strength. Routines should begin with warm-ups to
reduce the chances of injuries and end with cooldown exercises to speed recovery.
Stress reduction
Stress is a silent killer; chronic (long-term) stress
is a risk factor in many of the major diseases affecting
men’s mortality rates. Prolonged stress also may
GALE ENCYCLOPEDIA OF MEDICINE

cause ulcers, sleep disorders, addictions, depression,
anxiety, and other conditions. Reduction of stress
may require changes in both activities and attitudes.
Exercise is recommended, as is reducing dependence
on alcohol and nicotine. Men with extreme jobrelated stress may choose to spend more time with
their families or in enjoyable activities. Men with
stress levels that lead to destructive behaviors may
need to pursue psychotherapy or significant lifestyle
changes. Nutrition, social support, and healthy sleep
patterns also reduce stress.
Alternative therapies may help with stress reduction. Their use has been adopted by many leading
health centers. Biofeedback utilizes machines that
monitor users’ stress levels, helping people learn to
control them. Meditation and other mind/body techniques are taught to enable the relaxation response,
which has the opposite effects of stress in the body.
Testing
Routine physical examinations performed by
physicians are recommended every three years for
men in their twenties and thirties, every two years for
men in their forties, and every year for men over 50.
Physicians may order several screening tests as well,
depending on the age and condition of the patient.
Blood tests screen for diabetes, high cholesterol, cancer, infections, and HIV. The prostate-specific antigen
(PSA) test is a blood screen for prostate cancer. The
digital rectal exam is used to manually check the prostate gland for enlargement or irregularities. Urine tests
check for infections, kidney problems, and diabetes.
The fecal occult blood test examines the stool for
indications of ulcers or cancer. A sigmoidoscopy
checks the health of the rectum and lower colon.
Electrocardiograms (ECGs) check the status of the
heart. Older men may consult an ophthalmologist
(eye specialist) every two years for vision and glaucoma testing.
Men may perform self-tests as preventative measures. During a skin cancer self-exam, the entire skin is
checked closely for irregular or changing moles,
lesions, or blemishes, usually red, white or blue in
color. Abnormal findings should be reported to a
physician. Like some forms of skin cancer, testicular
cancer tends to spread rapidly and early detection is
crucial. The testicular self-exam is best performed in
the shower or bath, because warm water relaxes the
scrotum. The testicles are gently rolled and massaged
between the fingers and thumb to feel for bumps,
swelling, tenderness, or irregularities. Some self-test
kits are available in pharmacies, including kits for
blood pressure, high cholesterol, colorectal cancer,
2409

Men’s health

For American men, dietary problems are usually
not the result of getting too little nourishment but of
eating too much fat, sugar, and overall calories. The
dietary change most likely to improve the health of
males is reduced intake of fats, particularly cholesterol
and saturated fats. Cholesterol and saturated fats are
found mainly in meat and dairy products. Calories
from fat should amount to no more than 30% of
total daily calories. Eating adequate protein is generally not a problem for American men, so replacing
some dairy and meat consumption with high fiber
vegetable proteins such as beans and soy would be
beneficial. Complex carbohydrates should provide
the bulk of daily calories, such as those from whole
grains and legumes, while sugar intake such as in soft
drinks, desserts and processed foods, should be significantly reduced. Increasing dietary fiber is recommended by eating plenty of fresh fruits, vegetables,
whole grains, and legumes. Other principles of a
healthy diet are avoiding artificial and processed
foods, eating food that is as fresh and natural as
possible, drinking plenty of water, and avoiding
hydrogenated or partially hydrogenated oils, which
contain unhealthy substances called trans-fatty acids.
Overeating should be avoided as should snacking
between meals, and alcohol intake should be limited
to one or two glasses per day.

Men’s health

and blood glucose (diabetes). These do not take the
place of proper medical care, and physicians should be
consulted before their use.

testicular cancer. The ACS lists seven warning signs of
cancer:


Unusual bleeding or discharge



Changes in bowel or bladder patterns



Persistent sores



Lumps or irregularities on the body



Difficulty swallowing or indigestion



Changes in warts or moles



Persistent cough or hoarseness in the throat

Heart disease
Heart disease is the major cause of death among
men. It claims nearly 500,000 lives each year in the
United States and is more likely in men than women.
Heart disease can take several forms but the most
prevalent is coronary heart disease, in which the
blood vessels that supply the heart with oxygen
become blocked and the heart muscle becomes
increasingly stressed. Arteriosclerosis, a major factor,
is the hardening of arteries due to the accumulation of
fatty materials. Hypertension, or high blood pressure,
also poses major risks for both heart disease and
stroke. Angina pectoris is the chest pain associated
with the early stages of heart disease; more than
three million American men suffer from it. When the
blockage of blood supply to the heart becomes severe,
a myocardial infarction (heart attack) may occur,
which can be fatal.
The main symptom of angina pectoris is sharp
pain on the left side of the chest that may radiate
throughout the upper body. Other symptoms include
shortness of breath, dizziness, fatigue, and swelling in
the legs and ankles. Angina may be triggered by physical or emotional stress and lasts up to 30 minutes.
Heart attacks have similar symptoms but with longer
and more intense pain in the chest and upper body and
may be accompanied by cold sweats and vomiting.
The American Heart Association lists the main
risk factors for heart disease as being male, old age,
having family history of the disease, smoking, high
cholesterol, high blood pressure, diabetes, alcoholism,
obesity, physical inactivity and stress. Clearly, lifestyle
habits such as diet, exercise and stress control play
major roles in the development and prevention of
heart disease in men.
Cancer
The American Cancer Society (ACS) estimates
that more than 1.2 million cases of cancer were
reported in 2000. Men have a slightly higher risk for
cancer than women. The World Health Organization
(WHO) estimates that the number of cancer cases in
most countries will double in the next 25 years, while
men’s prostate cancer is expected to go up 40% worldwide. The most common cancers in men are skin,
prostate, lung, colorectal (colon and rectum), lymphoma (lymph glands), oral (mouth and throat), and

2410

Although the causes of cancer are incompletely
understood, there are several risk factors that increase
its chances: family history of cancer, smoking, poor
diet (high in fat, low in fiber), excessive alcohol consumption, skin damage from sunlight, and exposure to
radiation, chemicals, and environmental pollutants.
The prostate gland is a walnut-sized organ in the
male reproductive system, located near the rectum
below the bladder. The ACS reported that nearly
232,000 new cases of prostate cancer would be diagnosed in 2005, causing more than 30,000 deaths, making prostate cancer the second most fatal cancer for
men behind lung cancer. Worldwide studies have
shown that about 12% of men in Western countries
get prostate cancer, while 50% have enlarged prostates. Benign prostatic hyperplasia (BPH) is the enlargement of the prostate gland, called benign when it is
non-cancerous although growth can be rapid.
With early detection, 98% of men with prostate
cancer survive for five years. Symptoms of prostate
cancer include difficulty in stopping or starting urination, frequent nighttime urination (nocturia), weak
urine flow, and blood in the urine or semen.
Testicular cancer is most common in men between
the ages of 15 and 34. The ACS estimated that there
would be about 8,100 new cases of testicular cancer in
2005 in the United States. A 2004 study showed that
cigarette smoking increased risk of testicular cancer
and quitting smoking did not reduce the risk.
Stroke
Strokes occur when the blood supply to the brain
is interrupted and brain function becomes impaired
due to lack of oxygen. Ischemic strokes occur due to
blood vessels becoming blocked while hemorrhagic
strokes are the result of broken blood vessels in or
near the brain. Ischemic strokes account for about
80% of all strokes. The American Heart Association
estimates that more than 600,000 Americans suffer
from strokes each year, with men having a 20%
higher risk of stroke than women, although more
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms of strokes include sudden weakness or
numbness, blurring or loss of vision, difficulty speaking or understanding, sudden severe headache, and
dizziness or falling. Stroke victims should receive
immediate emergency care.
Male urinary tract problems
The urinary system includes the kidneys and
bladder, the ureters between the kidneys and bladder,
and the urethra, the tube through which urine flows
from the bladder. Symptoms of urinary tract problems include frequent urination, excessive urination
at night, painful or burning urination, weak urination, blood in the urine, or incontinence (involuntary
loss of urine). Urethritis is infection of the urethra,
which is a major symptom of sexually transmitted
diseases (STDs). Kidney stones (nephrolithiasis) are
the most common urinary tract problems, accounting for nearly one out of every 100 hospital admissions in the United States. Eighty percent of kidney
stone patients are men. About 12% of American men
will develop kidney stones during their lifetimes.
Kidney stones cause extreme pain when they move
from the kidneys into the ureters. Ten percent of
kidney stone cases require surgery. The best prevention for kidney stones is drinking plenty of fluids
daily.
The male reproductive system
The male reproductive system includes the penis,
testicles, scrotum, prostate and other organs.
Problems include orchitis, or infection of the testicles,
and hydrocele, the buildup of fluid on the testicles.
Epididymitis is inflammation of the tube that transports sperm from the testicles, and can cause severe
pain, swelling, and fever. A varicocele is a group of
varicose veins in the scrotum that can cause swelling
and damage sperm. Peyronie’s disease is the abnormal curvature of the penis caused by accumulated
scar tissue. Testicular torsion is considered a medical
emergency, when a testicle becomes twisted and
blood supply is cut off. This condition can lead to
permanent damage if not treated quickly. It is most
common in males between the ages of 12 and 18.
Prostatitis is infection or inflammation of the prostate gland.
GALE ENCYCLOPEDIA OF MEDICINE

Sexually transmitted diseases include genital
warts, chlamydia, gonorrhea, syphilis, genital herpes,
hepatitis and HIV (human immunodeficiency virus).
HIV is the leading cause of death for American men
between the ages of 25 and 45. Symptoms of STDs
include discharge of fluid from the penis; painful urination; sores, lesions, itching, or rashes in the genital
area; and swelling of the lymph nodes in the groin.
Prevention of STDs begins with safe sexual behavior:
wearing condoms, limiting the number of sexual partners, not mixing sexual encounters with alcohol, and
avoiding sexual contact with infected people, prostitutes and intravenous drug users. Men who engage in
risky behaviors should have frequent HIV tests and
medical examinations.
Male sexual health
Erectile dysfunction (ED), also called impotence, is
a man’s inability to maintain an erection for sexual
intercourse. It affects nearly one in every 10 American
men. Incidence of ED increases with age, but the
problem can occur at any age. Up to 80% of ED is
caused by physical problems, while 20% of cases are
psychogenic, or psychological in origin. Causes of ED
include hormonal problems, injuries, nerve damage,
diseases, infections, diabetes, stress, depression, anxiety, drug abuse, and interactions with prescription
drugs. ED also may be the first indication of circulation problems due to diabetes, high blood pressure, or
coronary artery disease.
A self-test men can perform to determine whether
ED is physical or psychological is the stamp test, or
nocturnal penile tumescence test. Physically healthy
men experience several prolonged erections during
sleep. The stamp test is done by attaching a strip of
stamps around the penis before bedtime; if the stamps
are torn in the morning, it generally indicates that
nocturnal (nightly) erections have occurred and thus
ED is not physiological. Men with ED should see a
urologist for further diagnosis and discussion of the
several treatment options available including drugs,
hormone injections, and surgical repair or implants.
Several new prescription drugs have become available
in recent years.
Infertility occurs when men lack an adequate supply of sperm to cause pregnancy. As many as 15% of
American couples, or more than 5 million Americans,
are affected by infertility in one or both partners. A
World Health Organization (WHO) project found
that in about 20% of infertile couples, the problem
was due to the man, while in another 27% of couples
both partners had infertility problems. Injuries, birth
defects, infections, environmental pollutants, chronic
2411

Men’s health

women die from strokes. Other risk factors are hypertension (high blood pressure), previous heart attacks,
age, family history, high cholesterol, smoking, obesity, alcoholism, and physical inactivity. African
Americans have 60% greater chances for strokes
than whites.

Men’s health

stress, drug abuse, and hormonal problems may
account for male infertility, while one in four cases
has no apparent cause and is termed idiopathic infertility. Declining sperm counts have been observed in
industrialized countries, and possible explanations for
this decrease are as diverse as increased environmental
pollutants to the use of plastic diapers, which a
German study claims damages infant testicles by keeping in excess heat. Male infertility can be diagnosed by
sperm analysis, blood tests, radiographic scans of the
testicles, and other tests.
Other types of sexual dysfunction include premature ejaculation, in which men cannot sustain intercourse long enough to bring their partners to climax,
and retarded ejaculation (also called male orgasmic
disorder) when male orgasm becomes difficult. Some
men have periods of inadequate sexual desire (hypoactive sexual desire disorder), while sexual aversion disorder (SAD) is fear and repulsion of sexual activity.
Dyspareunia is painful intercourse, and should be
reported to physicians as it may indicate STDs or
infections. In addition to medical care, sexual dysfunction may be treated by sex therapy or psychotherapy
depending on its causes.
Vasectomies, a form of male birth control, are
surgical operations that sever the tubes that transport
sperm from the testicles. Vasectomies can be reversed
but 10% of men become infertile due to the surgery.
Circumcision is the surgical removal of the foreskin of
the penis, for religious and medical reasons, performed on 60% of newborn males in the United
States. Increasing controversy surrounds this procedure. Advocates of circumcision claim it prevents
infections (called balanitis) on the head of the penis
and reduces chances of penile cancer. Opponents of
circumcision claim that the outdated procedure
affords no medical benefits, that it causes unnecessary
pain for infants, and that the lack of a foreskin may
reduce sexual pleasure and performance.
Men’s emotional health
Depression is a mood disorder marked by sadness, emotional pain, and the inability to feel pleasure.
At least 10% of men will experience an episode of
major depression at least once in their lives. Men
with depression are five times more likely to commit
suicide, a major cause of mortality in men. Men are
half as likely to seek psychological help than women.
Men may suffer depression and emotional problems
between the ages of 50 and 65, called the midlife crisis
as men face the major transition into retirement and
older age.
2412

KEY TERMS
Emphysema—Disease of severe lung deterioration
and impairment.
Obesity—Condition defined as being overweight
by 30% of normal limits.
Sigmoidoscopy—Test procedure using an optical
instrument to view the internal rectum and colon.
Urologist—Physician specializing in male reproductive and urinary systems.

Panic attacks have symptoms of overwhelming
fear, chest pain, shortness of breath, numbness, and
increased heart rate. Men may mistake them as heart
attacks. Men also are plagued by addictions to nicotine, alcohol, and other drugs, which are often the
unhealthy escape routes from deeper emotional issues.
Studies have estimated that as many as one-third of
Americans have suffered from sleep disorders, which
may be psychological in origin and related to anxiety,
stress and lifestyle.
Mental illness can be particularly difficult for men
because in our society men are taught to withhold
rather than express emotions and feelings. Emotional
problems can be strong signals for men to communicate and confront deeper issues. Help can be found
from physicians, psychotherapists, and spiritual or
religious counselors.
Osteoporosis
Osteoporosis often is thought of as disease more
prevalent in women, but more than two million men
have the disease characterized by decrease in bone
mass and density. It develops about 10 to 15 years
later in life in men than in women and risk of fractures from the disease can be greater in men. Men
can decrease their risk by increasing calcium and
vitamin D.
Resources
PERIODICALS

‘‘Cigarette Smoking Influences Testicular Cancer Risk.’’
Medical Devices & Surgical Technology Week March
28, 2004: 218.
‘‘Men’s Health: Erectile Dysfunction.’’ Medical Update
January 2004: 2.
‘‘Osteoporosis Develops Later in Men, Hits Harder.’’
Internal Medicine News March 15, 2004: 30.
GALE ENCYCLOPEDIA OF MEDICINE

American Foundation for Urologic Disease. 1128 N.
Charles St., Baltimore, MD 21201. (401) 468-1800.
<http://www.afud.org>.
Center for Holistic Urology. 161 Fort Washington Ave.,
New York, NY 10032. (212) 305-0347. <http://
www.holisticurology.com>.
OTHER

A Man’s Life Online Magazine. <http://
www.manslife.com>.
The Prostate Cancer Infolink. <http://www.comed.com/
prostate>.

Douglas Dupler, MA
Teresa G. Odle

Menstrual disorders
Definition
A menstrual disorder is a physical or emotional
problem that interferes with the normal menstrual
cycle, causing pain, unusually heavy or light bleeding,
delayed menarche, or missed periods.

Description
Typically, a woman of childbearing age should
menstruate every 28 days or so unless she is pregnant
or moving into menopause. But numerous things can
go wrong with the normal menstrual cycle, some the
result of physical causes, others emotional. These
include amenorrhea, or the cessation of menstruation,
menorrhagia, or heavy bleeding, and dysmenorrhea, or
severe menstrual cramps. Nearly every woman will
experience one or more of these menstrual irregularities at some time in her life.
Amenorrhea
There are two types of amenorrhea: primary and
secondary. Overall, they affect 2–5% of childbearing
women, a number that is considerably higher among
female athletes (possibly as high as 66%).
Primary amenorrhea occurs when a girl at least
16 years old is not menstruating. Young girls may not
have regular periods for their first year or two, or their
periods may be very light, a condition known as oligomenorrhea. A light flow is nothing to worry about. But
if the period has not begun at all by age 16, there may
be something wrong. Amenorrhea is most common in
GALE ENCYCLOPEDIA OF MEDICINE

girls who are severely underweight and/or exercise
intensely, both of which affect the amount of body
fat necessary to trigger the release of hormones that,
in turn, begins puberty.
Secondary amenorrhea occurs in women of childbearing age after a period of normal menstruation and
is diagnosed when menstruation has stopped for three
months. It can occur in women of any age.
Dysmenorrhea
Characterized by menstrual cramps or painful
periods, dysmenorrhea, which comes from the Greek
words for ‘‘painful flow,’’ affects nearly every woman
at some point in her life. It is the most common reproductive problem in women, resulting in numerous
days absent from school, work, and other activities.
There are two types: primary and secondary.
Primary, or normal cramps, affects up to 90% of
all women, usually occurring in women about three
years after they start menstruating and continuing
through their mid-twenties or until they have a child.
About 10% of women who have this type of dysmenorrhea cannot work, attend school, or participate in
their normal activities. It may be accompanied by
backache, dizziness, headache, nausea, vomiting, diarrhea and tenseness. The symptoms typically start a day
or two before menstruation, usually ending when menstruation actually begins.
Secondary dysmenorrhea has an underlying
physical cause and primarily affects older women,
although it may also occur immediately after a
woman begins menstruation.
Menorrhagia
Menorrhagia, or heavy bleeding, most commonly
occurs in the years just before menopause or just after
women start menstruating. It occurs in 15–20% of
American women.
Premenstrual dysphoric disorder (PMDD)
The fourth edition of the Diagnostic and
Statistical Manual of Mental Disorders, or DSM-IV,
lists premenstrual dysphoric disorder (PMDD) in an
appendix of criteria sets for further study. To meet
full criteria for PMDD, a patient must have at least
five out of 11 emotional or physical symptoms during
the week preceding the menses for most menstrual
cycles over the previous 12 months. Although the
DSM-IV definition of PMDD as a mental disorder is
controversial because of fear that it could be used to
justify prejudice or job discrimination against women,
2413

Menstrual disorders

ORGANIZATIONS

Menstrual disorders

there is evidence that a significant proportion of premenopausal women suffer emotional distress or
impairment in job functioning in the week before
their menstrual period. One group of researchers estimates that 3–8% of women of childbearing age meet
the strict DSM-IV criteria for PMDD, with another
13–18% having symptoms severe enough to interfere
with their normal activities.

Causes and symptoms
Amenorrhea
The only symptom of primary amenorrhea is
delayed menstruation. In addition to low body
weight or excessive exercise, other causes of primary
amenorrhea include Turner’s syndrome, a birth
defect related to the reproductive system, or ovarian
problems. In 2003, a group of researchers reported on
a new genetic mutation associated with primary amenorrhea. In secondary amenorrhea, the primary
symptom is the ceasing of menstruation for at least
three months. Causes include pregnancy or breastfeeding, sudden weight loss or gain, intense exercise,
stress, endocrine disorders affecting the thyroid,
pituitary or adrenal glands, including Cushing’s
Syndrome and hyperthyroidism, problems with or
surgery on the ovaries, including removal of the ovaries, cysts or ovarian tumors.
Amenorrhea in athletes or dancers is frequently
associated with two other disorders—osteopenia, or
reduced bone mass, and eating disorders. This combination is sometimes called the female athlete triad.
Osteopenia is of concern because it can lead to premature osteoporosis.
Dysmenorrhea
Primary dysmenorrhea is related to the production of prostaglandins, natural chemicals the body
makes that cause an inflammatory reaction. They
also cause the muscles of the uterus to contract,
thus helping the uterus shed the lining built up during
the first part of a woman’s cycle. Women with severe
menstrual pain have higher levels of prostaglandin
in their menstrual blood than women who do not
have such pain. In some women, prostaglandins can
cause some of the smooth muscles in the gastrointestinal tract to contract, resulting in the nausea,
vomiting and diarrhea some women experience.
Prostaglandins also cause the arteries and veins to
expand, so that blood collects in them rather than
flowing freely through them, causing pain and heaviness. Yet another reason for severe cramps,
2414

particularly in women who have not yet had a baby,
is that the flow of the blood and clots through the tiny
cervical opening is painful. After a woman has a
baby, however, the cervix opening is larger.
Secondary dysmenorrhea is more serious and is
related to some underlying cause. The pain may feel
like regular menstrual cramps, but may last longer
than normal and occur throughout the month. It
may be stronger on one side of the body than the
other. Possible causes include:


A tipped uterus



Endometriosis, a condition in which the same type of
tissue found in the lining of the uterus occurs outside
the uterus, usually elsewhere in the pelvic cavity



Adenomyosis, a condition in which the endometrial
lining grows into the muscle of the uterus



Fibroids



Pelvic inflammatory disease (PID)



An IUD



A uterine, ovarian, bowel or bladder tumor



Uterine polyps



Inflammatory bowel disease



Scarring or adhesions from earlier surgery
Menorrhagia

Heavy bleeding during menstruation is usually
related to a hormonal imbalance, although other causes
include fibroids, cervical or endometrial polyps, the
autoimmune disease lupus, pelvic inflammatory disease
(PID), blood platelet disorder, a hereditary blood factor deficiency, or, possibly, some reproductive cancers.
Thus, menorrhagia is actually a symptom of an underlying condition rather than a disease itself. It may also
be related to the use of an IUD.
Women with menorrhagia experience not only
significant inconvenience, but may feel very tired due
to the loss of iron-rich blood. It is usually diagnosed
when a woman soaks through a tampon or pad every
hour for several hours or has a period lasting more
than 7 days. Clots are not related to menorrhagia,
although women with heavy cycles may pass clots.
They are typically a normal part of menstruation,
more common when a woman has been sitting or in
a stationary position for a while

Diagnosis
Women should seek care from a gynecologist,
family practitioner or internist for menstrual
GALE ENCYCLOPEDIA OF MEDICINE

Male doctors typically have a female nurse or
assistant in the room. The examination begins by
checking the external genitalia for any sores or irregularities. Then the doctor inserts a speculum (a metal
duckbill-shaped device that holds open the vagina)
into the vagina and peers throughout the opening to
evaluate the health of the cervix (opening of the
uterus), and inside the vagina, looking for growths or
any other abnormalities.
The doctor will also manually examine the
woman, inserting two fingers into the vagina while
pressing on the abdomen, again feeling for any lumps
or other abnormalities, checking the size and shape of
the reproductive organs, and watching for any signs of
infection, such as tenderness or pain. The exam is
typically covered by insurance and takes about 10
minutes.
Other tests that will be done for menstrual irregularities include:


A pregnancy test. The nurse takes some blood from a
woman’s arm and it is tested for the presence of
certain hormones that indicate a pregnancy has
occurred.



Ultrasound. Typically performed by a trained ultrasound technologist, it involves using sound waves to
get an image of the reproductive system. It is used to
look for fibroids and other ovarian abnormalities
that may cause heavy bleeding or cramps.
Typically, the technologist will smear a jelly over
the woman’s stomach, then place a probe on her
stomach and watch the images appear on a computer
screen. It is painless. Women may be asked not to
urinate for several hours prior to the test, as a full
bladder makes it easier to see the other internal
organs. The test takes about 20 minutes.



Endometrial biopsy. Used to check the health of
uterine tissue in women who have unusually heavy
bleeding, this test should be performed by the physician. Women should take a pain reliever such as
ibuprofen or naproxen prior to the procedure, as
there may be some cramping. The woman lies back
on the table with her feet in stirrups and the doctor
inserts a speculum, then opens the cervix slightly with
an instrument called a tenaculum. Then the doctor
slides a small, hollow catheter into the uterus and
sucks out a small piece of tissue from the uterine
lining. The tissue is then examined for any

GALE ENCYCLOPEDIA OF MEDICINE

abnormalities in a laboratory. The test takes about
30 minutes and is typically covered by insurance.
Some bleeding may result afterwards.


Blood, stool and urine tests may also be conducted to
check for levels of various hormones, blood cells, and
other chemicals.



Dilation and curettage (D&C): During this minor
surgical procedure, the cervix is opened and the lining of the uterus scraped for a tissue sample.



Laparascopy and hysteroscopy: in some instances,
these surgical procedures, in which a small camera
is inserted into the woman to view the inside of the
pelvis, abdomen or uterus.

Treatment
Amenorrhea
For primary amenorrhea with no underlying
problem, no treatment is necessary, and a wait-andsee approach is often adopted. If women have genetic
or hormonal abnormalities, amenorrhea is often treated with oral contraceptives that contain combinations of estrogen and progestin. Side effects include
bloating, weight gain and acne, although some birth
control pills actually improve acne. Progestins, or
synthetic progesterone, are also used alone to ‘‘jump
start’’ a woman’s period. They include medroxyprogesterone (Provera, Amen, Depo-Provera), norethindrone acetate (Aygestin, Norlutate), and norgestrel
(Ovrel). If the amenorrhia is due to a physical problem, such as a closed vagina, surgery may be
required.
With secondary amenorrhia, treatment depends
on the cause. Hormonal imbalances are treated with
supplemental hormones. Tumors or cysts may require
surgery. Obesity may require a diet and exercise regimen, while amenorrhia resulting from too much dieting or exercise necessitates lifestyle changes.
Dysmenorrhea
Primary dysmenorrhea is typically treated with
nonsteroidal anti-inflammatory medications like ibuprofen and naproxen, which studies show help 64 to
100% of women. Birth control pills relieve pain and
symptoms in about 90% of women by suppressing
ovulation and reducing the amount of menstrual
blood. It may take up to three cycles before a woman
feels relief. Heat from a heating pad or hot bath, can
also help relieve pain.
Treatment for secondary dysmenorrhea depends
on the underlying cause of the condition.
2415

Menstrual disorders

irregularities. Depending on the problem, various tests
and procedures will be performed, but the one common to any menstrual problem is a pelvic exam. This
should be scheduled when women are not menstruating, simply for conveniencee.

Menstrual disorders

that women with low amounts of omega-3 fatty acids
in their diets were more likely to have menstrual
cramps; those who took supplements had less pain.

Menorrhagia
If there are no other problems, and the bleeding is
due to hormonal imbalances, birth control pills are
often prescribed to bring the bleeding under control
and regulate menstruation. Such medications as ibuprofen and naproxen can also help reduce the bleeding
and any cramping associated with it. In severe cases,
doctors may recommend removing the uterus during a
hysterectomy, or performing some form of endometrial
ablation, which removes the lining of the uterus. These
procedures are typically only offered to women who
have completed their families. A recent British study
reported, however, that many women prefer endometrial ablation to hysterectomy because it is less invasive
and safer. A new treatment that involves intrauterine
hormonal therapy is gaining acceptance, but had not
been approved by the FDA as of spring 2004.
Premenstrual dysphoric disorder (PMDD)
Medications that have been reported to be effective in treating PMDD include the tricyclic antidepressants and the selective serotonin reuptake inhibitors
(SSRIs). Effective treatments other than medications
include cognitive behavioral therapy (CBT), aerobic
exercise, and dietary supplements containing calcium,
magnesium, and vitamin B6.

Alternative treatment



Vitamin B-1: One large study found that symptoms
disappeared in 87% of women who took 100 mg a
day for 90 days.



Magnesium supplements: One study of 30 women
who took 4.5 milligrams of oral magnesium three
times daily for part of the month decreased their
symptoms up to 84%.
Menorrhagia

Herbs used to treat menorrhagia include yarrow,
nettles and shepherd’s purse, as well as agrimony,
particularly used in Chinese medicine, ladies mantle,
vervain and red raspberry, which are thought to
strengthen the uterus. Vitex is another herb recommended for a variety of menstrual disorders ranging
from menorrhagia to PMS. Women may want to
make sure they are taking an iron supplement to replace
the iron lost during the heavy bleeding, although they
should check with their doctor to make sure they do not
suffer from a condition of having too much iron.
Helpful vitamins include vitamin A, because women
with heavy bleeding typically have lower levels of
Vitamin A, K, which aids in clotting, and C and bioflavinoids which help strengthen veins and capillaries.
Zinc may also help.

Amenorrhea
There are several herbal remedies that can bring
on menstruation, including: black cohosh, cramp
bark, chasteberry, celery, turmeric, and marsh mallow. Numerous relaxation techniques, such as meditation, deep breathing, and yoga can help reduce stress
and its affects on menstruation.

Prognosis
The prognosis for all menstrual irregularities is
good once treatment is initiated.

Prevention
Amenorrhea

Dysmenorrhea
Numerous alternative treatments may help relieve
the menstrual pain. These include:


Transcutaneous electrical nerve stimulation (TENS),
which several studies found, relieved pain in 42–60%
of participants, working faster than naproxen in one
study.



Acupuncture: One study of 43 patients followed for a
year found that 90% of those who had acupuncture
once a week for three menstrual cycles had less pain,
and 43% used less pain medication.



Omega-3 fatty acids: Often sold as fish oil supplements, they are a known anti-inflammatory, working
against the effects of prostaglandins. Studies found

2416

Simply following a healthy exercise and nutritional program can help prevent amenorrhea, as can
reducing stress and learning relaxation techniques.
Also, avoiding excessive alcohol intake and quitting
smoking may prevent missed periods.
Dysmenorrhea
Prevention includes certain dietary supplements
and vitamins described above. Exercise may also help.
Menorrhagia
There is little women can do to prevent this menstrual irregularity other than discovering the root
GALE ENCYCLOPEDIA OF MEDICINE

Adenomyosis—Uterine thickening caused when
endometrial tissue, which normally lines the
uterus, extends outward into the fibrous and muscular tissue of the uterus.
Cervical polyps—Growths originating from the surface of the cervix or endocervical canal. These
small, fragile growths hang from a stalk and protrude through the cervical opening (the os).
Cushing’s syndrome—A group of conditions
caused by increased production of cortisol hormones or by the administration of glucocorticoid
hormones (cortisone-like hormones).
Endometriosis—A condition in which the tissue
that normally lines the uterus (endometrium)
grows in other areas of the body, causing pain,
irregular bleeding, and frequently, infertility.
Fibroids—Benign tumors of muscle and connective
tissue that develop within or are attached to the
uterine wall.
Hyperthyroidism—An imbalance in metabolism
that occurs from overproduction of thyroid
hormone.
Inflammatory bowel disease—A chronic inflammatory disease that can affect any part of the gastrointestinal tract but most commonly affects the
ileum.
Lupus (systemic lupus erythematosus or SLE)—A
chronic inflammatory autoimmune disorder that
may affect many organ systems including the skin,
joints, and internal organs.
Menarche—The first menstrual period or the establishment of the menstrual function.
Osteopenia—Reduction in bone mass, usually
caused by a lowered rate of formation of new
bone that is insufficient to keep up with the rate of
bone destruction. Osteopenia often occurs together
with amenorrhea and eating disorders in female
athletes. It can lead to premature osteoporosis if
left untreated.
Pelvic inflammatory disease (PID)—A general
term referring to infection involving the lining of
the uterus, the Fallopian tubes, or the ovaries.
Turner’s syndrome—A disorder in women caused
by an inherited chromosomal defect. This disorder inhibits sexual development and causes
infertility. A symptom is absence of menstruation.

GALE ENCYCLOPEDIA OF MEDICINE

cause. One thing they can do, however, is stop using an
IUD, which can often cause heavier bleeding.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, DC: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Menstrual Abnormalities and Abnormal Uterine
Bleeding.’’ Section 18, Chapter 235. In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II. ‘‘CAM Therapies for Specific Conditions:
Menstrual Symptoms, Menopause, and PMS.’’ New
York: Simon & Schuster, 2002.
PERIODICALS

Aegerter, Ch., D. Friess, and L. Alberio. ‘‘Menorrhagia
Caused by Severe Hereditary Factor VII Deficiency.
Case 1.’’ Hämostaseologie 23 (August 2003): 99–102.
Donaldson, M. L. ‘‘The Female Athlete Triad. A Growing
Health Concern.’’ Orthopedic Nursing 22 (SeptemberOctober 2003): 322–324.
Halbreich, U., J. Borenstein, T. Pearlstein, and L. S. Kahn.
‘‘The Prevalence, Impairment, Impact, and Burden of
Premenstrual Dysphoric Disorder (PMS/PMDD).’’
Psychoneuroendocrinology 28, Supplement 3 (August
2003): 1–23.
Meduri, G., P. Touraine, I. Beau, et al. ‘‘Delayed Puberty
and Primary Amenorrhea Associated with a Novel
Mutation of the Human Follicle-Stimulating Hormone
Receptor: Clinical, Histological, and Molecular
Studies.’’ Journal of Clinical Endocrinology and
Metabolism 88 (August 2003): 3491–3498.
Paddison, K. ‘‘Menorrhagia: Endometrial Ablation or
Hysterectomy?’’ Nursing Standard 18 (September
17–23): 33–37.
Rapkin, A. ‘‘A Review of Treatment of Premenstrual
Syndrome and Premenstrual Dysphoric Disorder.’’
Psychoneuroendocrinology 28, Supplement 3 (August
2003): 39–53.
‘‘Research Eyes IUS Use for Menstrual Bleeding.’’
Contraceptive Technology Update Supplement 3 (June
2004): 67–69.
ORGANIZATIONS

Advancement of Women’s Health Research. 1828 L Street,
N.W., Suite 625 Washington, DC 20036. 202-223-8224.
<http://www.womens-health.org>.
American College of Obstetricians and Gynecologists
(ACOG). 409 12th Street, SW, P. O. Box 96920,
Washington, DC 20090-6920. <http://
www.acog.org>.
American Psychiatric Association (APA). 1400 K Street,
NW, Washington, DC 20005. (888) 357-7924.
<http://www.psych.org>.
2417

Menstrual disorders

KEY TERMS

Mental retardation

National Women’s Health Resource Center. 120 Albany
Street Suite 820, New Brunswick, NJ 08901. (877)
986-9472. <www.healthywomen.org>.

Debra Gordon
Rebecca J. Frey, PhD
Teresa G. Odle

Menstrual pain see Dysmenorrhea

with social, communication, and functional academic
skills. Children who have a neurological disorder or
illness such as encephalitis or meningitis may suddenly
show signs of cognitive impairment and adaptive
difficulties.
Mental retardation varies in severity. The
Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV ) is the diagnostic standard
for mental healthcare professionals in the United
States. The DSM-IV classifies four different degrees of
mental retardation: mild, moderate, severe, and profound. These categories are based on the functioning
level of the individual.

Mental retardation
Definition
Mental retardation is a developmental disability
that first appears in children under the age of 18. It is
defined as an intellectual functioning level (as measured by standard tests for intelligence quotient) that
is well below average and significant limitations in
daily living skills (adaptive functioning).

Description
Mental retardation occurs in 2.5–3% of the general population. About 6–7.5 million mentally
retarded individuals live in the United States alone.
Mental retardation begins in childhood or adolescence before the age of 18. In most cases, it persists
throughout adulthood. A diagnosis of mental retardation is made if an individual has an intellectual
functioning level well below average and significant
limitations in two or more adaptive skill areas.
Intellectual functioning level is defined by standardized tests that measure the ability to reason in terms
of mental age (intelligence quotient or IQ). Mental
retardation is defined as IQ score below 70–75.
Adaptive skills are the skills needed for daily life.
Such skills include the ability to produce and understand language (communication); home-living skills;
use of community resources; health, safety, leisure,
self-care, and social skills; self-direction; functional
academic skills (reading, writing, and arithmetic);
and work skills.
In general, mentally retarded children reach developmental milestones such as walking and talking
much later than the general population. Symptoms
of mental retardation may appear at birth or later in
childhood. Time of onset depends on the suspected
cause of the disability. Some cases of mild mental
retardation are not diagnosed before the child enters
preschool. These children typically have difficulties
2418

Mild mental retardation
Approximately 85% of the mentally retarded
population is in the mildly retarded category. Their
IQ score ranges from 50–75, and they can often
acquire academic skills up to the 6th grade level.
They can become fairly self-sufficient and in some
cases live independently, with community and social
support.
Moderate mental retardation
About 10% of the mentally retarded population is
considered moderately retarded. Moderately retarded
individuals have IQ scores ranging from 35–55. They
can carry out work and self-care tasks with moderate
supervision. They typically acquire communication
skills in childhood and are able to live and function
successfully within the community in a supervised
environment such as a group home.
Severe mental retardation
About 3–4% of the mentally retarded population
is severely retarded. Severely retarded individuals have
IQ scores of 20–40. They may master very basic selfcare skills and some communication skills. Many
severely retarded individuals are able to live in a
group home.
Profound mental retardation
Only 1–2% of the mentally retarded population is
classified as profoundly retarded. Profoundly retarded
individuals have IQ scores under 20–25. They may be
able to develop basic self-care and communication
skills with appropriate support and training. Their
retardation is often caused by an accompanying neurological disorder. The profoundly retarded need a
high level of structure and supervision.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Low IQ scores and limitations in adaptive skills
are the hallmarks of mental retardation.
Aggression, self-injury, and mood disorders are
sometimes associated with the disability. The severity of the symptoms and the age at which they first
appear depend on the cause. Children who are
mentally retarded reach developmental milestones
significantly later than expected, if at all. If retardation is caused by chromosomal or other genetic
disorders, it is often apparent from infancy. If
retardation is caused by childhood illnesses or injuries, learning and adaptive skills that were once
easy may suddenly become difficult or impossible
to master.
In about 35% of cases, the cause of mental
retardation cannot be found. Biological and environmental factors that can cause mental retardation
include:
Genetics
About 5% of mental retardation is caused by
hereditary factors. Mental retardation may be
caused by an inherited abnormality of the genes,
such as fragile X syndrome. Fragile X, a defect in
the chromosome that determines sex, is the most
common inherited cause of mental retardation.
Single gene defects such as phenylketonuria (PKU)
and other inborn errors of metabolism may also
cause mental retardation if they are not found and
treated early. An accident or mutation in genetic
development may also cause retardation. Examples
of such accidents are development of an extra
chromosome 18 (trisomy 18) and Down syndrome.
GALE ENCYCLOPEDIA OF MEDICINE

Down syndrome, also called mongolism or trisomy
21, is caused by an abnormality in the development
of chromosome 21. It is the most common genetic
cause of mental retardation.
Prenatal illnesses and issues
Fetal alcohol syndrome affects one in 600 children
in the United States. It is caused by excessive alcohol
intake in the first twelve weeks (trimester) of pregnancy. Some studies have shown that even moderate
alcohol use during pregnancy may cause learning disabilities in children. Drug abuse and cigarette smoking
during pregnancy have also been linked to mental
retardation.
Maternal infections and illnesses such as glandular disorders, rubella, toxoplasmosis, and cytomegalovirus infection may cause mental retardation. When
the mother has high blood pressure (hypertension) or
blood poisoning (toxemia), the flow of oxygen to the
fetus may be reduced, causing brain damage and mental retardation.
Birth defects that cause physical deformities of the
head, brain, and central nervous system frequently
cause mental retardation. Neural tube defect, for
example, is a birth defect in which the neural tube
that forms the spinal cord does not close completely.
This defect may cause children to develop an accumulation of cerebrospinal fluid on the brain (hydrocephalus). Hydrocephalus can cause learning impairment by
putting pressure on the brain.
Childhood illnesses and injuries
Hyperthyroidism, whooping cough, chickenpox,
measles, and Hib disease (a bacterial infection) may
cause mental retardation if they are not treated adequately. An infection of the membrane covering the
brain (meningitis) or an inflammation of the brain
itself (encephalitis) cause swelling that in turn may
cause brain damage and mental retardation.
Traumatic brain injury caused by a blow or a violent
shake to the head may also cause brain damage and
mental retardation in children.
Environmental factors
Ignored or neglected infants who are not provided
the mental and physical stimulation required for normal development may suffer irreversible learning
impairments. Children who live in poverty and suffer
from malnutrition, unhealthy living conditions, and
improper or inadequate medical care are at a higher
risk. Exposure to lead can also cause mental retardation. Many children have developed lead poisoning by
2419

Mental retardation

The American Association on Mental
Retardation (AAMR) has developed another widely
accepted diagnostic classification system for mental
retardation. The AAMR classification system focuses
on the capabilities of the retarded individual rather
than on the limitations. The categories describe the
level of support required. They are: intermittent support, limited support, extensive support, and pervasive
support. To some extent, the AAMR classification
mirrors the DSM-IV classification. Intermittent support, for example, is support needed only occasionally,
perhaps during times of stress or crisis. It is the type of
support typically required for most mildly retarded
individuals. At the other end of the spectrum, pervasive support, or life-long, daily support for most adaptive areas, would be required for profoundly retarded
individuals.

Mental retardation

eating the flaking lead-based paint often found in
older buildings.

Diagnosis
If mental retardation is suspected, a comprehensive physical examination and medical history should
be done immediately to discover any organic cause of
symptoms. Conditions such as hyperthyroidism and
PKU are treatable. If these conditions are discovered
early, the progression of retardation can be stopped
and, in some cases, partially reversed. If a neurological
cause such as brain injury is suspected, the child may
be referred to a neurologist or neuropsychologist for
testing.
A complete medical, family, social, and educational history is compiled from existing medical and
school records (if applicable) and from interviews
with parents. Children are given intelligence tests to
measure their learning abilities and intellectual functioning. Such tests include the Stanford-Binet
Intelligence Scale, the Wechsler Intelligence Scales,
the Wechsler Preschool and Primary Scale of
Intelligence, and the Kaufmann Assessment Battery
for Children. For infants, the Bayley Scales of Infant
Development may be used to assess motor, language,
and problem-solving skills. Interviews with parents
or other caregivers are used to assess the child’s daily
living, muscle control, communication, and social
skills.
The
Woodcock-Johnson
Scales
of
Independent Behavior and the Vineland Adaptive
Behavior Scale (VABS) are frequently used to test
these skills.

Treatment
Federal legislation entitles mentally retarded
children to free testing and appropriate, individualized education and skills training within the school
system from ages 3–21. For children under the age of
three, many states have established early intervention
programs that assess, recommend, and begin treatment programs. Many day schools are available to
help train retarded children in basic skills such as
bathing and feeding themselves. Extracurricular
activities and social programs are also important in
helping retarded children and adolescents gain selfesteem.
Training in independent living and job skills is
often begun in early adulthood. The level of training
depends on the degree of retardation. Mildly retarded
individuals can often acquire the skills needed to live
independently and hold an outside job. Moderate to
2420

profoundly retarded individuals usually require supervised community living.
Family therapy can help relatives of the mentally retarded develop coping skills. It can also
help parents deal with feelings of guilt or anger.
A supportive, warm home environment is essential
to help the mentally retarded reach their full
potential.

Prognosis
Individuals with mild to moderate mental retardation are frequently able to achieve some self-sufficiency and to lead happy and fulfilling lives. To reach
these goals, they need appropriate and consistent educational, community, social, family, and vocational
supports. The outlook is less promising for those
with severe to profound retardation. Studies have
shown that these individuals have a shortened life
expectancy. The diseases that are usually associated
with severe retardation may cause the shorter life
span. People with Down syndrome will develop the
brain changes that characterize Alzheimer’s disease in
later life and may develop the clinical symptoms of this
disease as well.

Prevention
Immunization against diseases such as measles
and Hib prevents many of the illnesses that can
cause mental retardation. In addition, all children
should undergo routine developmental screening as
part of their pediatric care. Screening is particularly
critical for those children who may be neglected or
undernourished or may live in disease-producing
conditions. Newborn screening and immediate treatment for PKU and hyperthyroidism can usually
catch these disorders early enough to prevent
retardation.
Good prenatal care can also help prevent retardation. Pregnant women should be educated about the
risks of drinking and the need to maintain good nutrition during pregnancy. Tests such as amniocentesis and
ultrasonography can determine whether a fetus is
developing normally in the womb.
Resources
ORGANIZATIONS

American Association on Mental Retardation (AAMR).
444 North Capitol St., NW, Suite 846, Washington,
D.C. 20001-1512. (800) 424-3688. <http://
www.aamr.org>.
The Arc. 900 Varnum Street NE, Washington, D.C. 20017.
(202) 636-2950. <http://thearc.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Amniocentesis—A test usually done between 16 and
20 weeks of pregnancy to detect any abnormalities
in the development of the fetus. A small amount of
the fluid surrounding the fetus (amniotic fluid) is
drawn out through a needle inserted into the
mother’s womb. Laboratory analysis of this fluid
can detect various genetic defects, such as Down
syndrome, or neural tube defects.

not have certain enzymes that the body requires to
maintain organ functions. Inborn errors of metabolism can cause brain damage and mental retardation
if left untreated. Phenylketonuria is an inborn error of
metabolism.

Developmental delay—The failure to meet certain
developmental milestones, such as sitting, walking,
and talking, at the average age. Developmental
delay may indicate a problem in development of
the central nervous system.

Phenylketonuria (PKU)—An inborn error in metabolism that prevents the body from using phenylalanine, an amino acid necessary for normal growth
and development.

Down syndrome—A disorder caused by an abnormality at the 21st chromosome. One symptom of
Down syndrome is mental retardation.
Extensive support—Ongoing daily support required
to assist an individual in a specific adaptive area,
such as daily help with preparing meals.
Hib disease—An infection caused by Haemophilus
influenza type b (Hib). This disease mainly affects
children under the age of five. In that age group, it is
the leading cause of bacterial meningitis, pneumonia,
joint and bone infections, and throat inflammations.
Inborn error of metabolism—A rare enzyme deficiency; children with inborn errors of metabolism do

OTHER

Americans With Disabilities Act (ADA) Page. <http://
www.usdoj.gov/crt/ada/adahom1.htm>.

Paula Anne Ford-Martin

Mental status examination
Definition
A mental status examination (MSE) is an assessment of a patient’s level of cognitive (knowledgerelated) ability, appearance, emotional mood, and
speech and thought patterns at the time of evaluation.
It is one part of a full neurologic (nervous system)
examination and includes the examiner’s observations
about the patient’s attitude and cooperativeness as
well as the patient’s answers to specific questions.
GALE ENCYCLOPEDIA OF MEDICINE

Limited support—A predetermined period of assistance required to deal with a specific event, such as
training for a new job.

Trisomy—An abnormality in chromosomal development. Chromosomes are the structures within a
cell that carry its genetic information. They are
organized in pairs. Humans have 23 pairs of chromosomes. In a trisomy syndrome, an extra chromosome is present so that the individual has three of a
particular chromosome instead of the normal pair.
An extra chromosome 18 (trisomy 18) causes mental retardation.
Ultrasonography—A process that uses the reflection of high-frequency sound waves to make an
image of structures deep within the body.
Ultrasonography is routinely used to detect fetal
abnormalities.

The most commonly used test of cognitive functioning
per se is the so-called Folstein Mini-Mental Status
Examination (MMSE), developed in 1975.

Purpose
The purpose of a mental status examination is to
assess the presence and extent of a person’s mental
impairment. The cognitive functions that are measured during the MSE include the person’s sense of
time, place, and personal identity; memory; speech;
general intellectual level; mathematical ability; insight
or judgment; and reasoning or problem-solving ability. Complete MSEs are most commonly given to
elderly people and to other patients being evaluated
for dementia (including AIDS-related dementia).
Dementia is an overall decline in a person’s intellectual
function—including difficulties with language, simple
calculations, planning or decision-making, and motor
(muscular movement) skills as well as loss of memory.
The MSE is an important part of the differential
2421

Mental status examination

KEY TERMS

Mental status examination

diagnosis of dementia and other psychiatric symptoms
or disorders. The MSE results may suggest specific
areas for further testing or specific types of required
tests. A mental status examination can also be given
repeatedly to monitor or document changes in a
patient’s condition.

Precautions



Thought process. Thought process refers to the logical connections between thoughts and their relevance
to the main thread of conversation. Irrelevant detail,
repeated words and phrases, interrupted thinking
(thought blocking), and loose, illogical connections
between thoughts, may be signs of a thought
disorder.



Cognition. Cognition refers to the act or condition of
knowing. The evaluation assesses the person’s orientation (ability to locate himself or herself) with
regard to time, place, and personal identity; longand short-term memory; ability to perform simple
arithmetic (counting backward by threes or sevens);
general intellectual level or fund of knowledge (identifying the last five Presidents, or similar questions);
ability to think abstractly (explaining a proverb);
ability to name specified objects and read or write
complete sentences; ability to understand and perform a task (showing the examiner how to comb
one’s hair or throw a ball); ability to draw a simple
map or copy a design or geometrical figure; ability to
distinguish between right and left.



Judgment. The examiner asks the person what he or
she would do about a commonsense problem, such as
running out of a prescription medication.



Insight. Insight refers to a person’s ability to recognize a problem and understand its nature and
severity.

The MSE cannot be given to a patient who cannot
pay attention to the examiner, for example as a result
of being in a coma or unconscious; or is completely
unable to speak (aphasic); or is not fluent in the language of the examiner.

Description
The MMSE of Folstein evaluates five areas of
mental status, namely, orientation, registration, attention and calculation, recall and language. A complete
MSE is more comprehensive and evaluates the following ten areas of functioning:




Appearance. The examiner notes the person’s age,
race, sex, civil status, and overall appearance. These
features are significant because poor personal
hygiene or grooming may reflect a loss of interest in
self-care or physical inability to bathe or dress
oneself.
Movement and behavior. The examiner observes the
person’s gait (manner of walking), posture, coordination, eye contact, facial expressions, and similar
behaviors. Problems with walking or coordination
may reflect a disorder of the central nervous system.



Affect. Affect refers to a person’s outwardly observable emotional reactions. It may include either a
lack of emotional response to an event or an
overreaction.



Mood. Mood refers to the underlying emotional
‘‘atmosphere’’ or tone of the person’s answers.



Speech. The examiner evaluates the volume of the
person’s voice, the rate or speed of speech, the length
of answers to questions, the appropriateness and
clarity of the answers, and similar characteristics.



Thought content. The examiner assesses what the
patient is saying for indications of hallucinations,
delusions, obsessions, symptoms of dissociation, or
thoughts of suicide. Dissociation refers to the splitting-off of certain memories or mental processes
from conscious awareness. Dissociative symptoms
include feelings of unreality, depersonalization, and
confusion about one’s identity.

2422

The length of time required for a mental status
examination depends on the patient’s condition. It
may take as little as five minutes to examine a healthy
person. Patients with speech problems or intellectual
impairments, dementia, or other organic brain disorders may require fifteen or twenty minutes. The examiner may choose to spend more time on certain
portions of the MSE and less time on others, depending on the patient’s condition and answers.

Preparation
Preparation for a mental status examination
includes a careful medical and psychiatric history of
the patient. The history helps the examiner to interpret
the patient’s appearance and answers with greater
accuracy, because some physical illnesses may produce psychiatric symptoms or require medications
that influence the patient’s mood or attentiveness.
The psychiatric history should include a family history
as well as the patient’s personal history of development, behavior patterns, and previous treatment for
mental disorders (if any). Symptoms of dissociation,
for example, often point to a history of childhood
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Aphasia—The loss of the ability to speak, or to understand written or spoken language. A person who cannot speak or understand language is said to be aphasic.
Cognition—The act or process of knowing or
perceiving.
Coma—A state of prolonged unconsciousness in
which a person cannot respond to spoken commands or mildly painful physical stimuli.
Delusion—A belief that is resistant to reason or
contrary to actual fact. Common delusions include
delusions of persecution, delusions about one’s
importance (sometimes called delusions of grandeur), or delusions of being controlled by others.
Dementia—A decline in a person’s level of intellectual functioning. Dementia includes memory
loss as well as difficulties with language, simple
calculations, planning or decision-making, and
motor (muscular movement) skills.
Dissociation—The splitting off of certain mental processes from conscious awareness. Specific symptoms
of dissociation include feelings of unreality, depersonalization, and confusion about one’s identity.
Hallucination—A sensory experience, usually
involving either sight or hearing, of something that
does not exist outside the mind.

Aftercare
Depending on the examiner’s specific observations, the patient may be given additional tests for
follow-up. These tests might include blood or urine
samples to test for drug or alcohol abuse, anemia,
diabetes, disorders of the liver or kidneys, vitamin or
thyroid deficiencies, medication side effects, or syphilis
and AIDS. Brain imaging (CT, MRI, or PET scans)
may be used to look for signs of seizures, strokes, head
trauma, brain tumors, or other evidence of damage to
specific parts of the brain. A spinal tap may be performed if the doctor thinks the patient may have an
infection of the central nervous system.

Normal results
Normal results for a mental status examination
depend to some extent on the patient’s history, level of
education, and recent life events. For example, a
depressed mood is appropriate in the context of a
recent death or other sad event in the patient’s family
but inappropriate in the context of a recent pay raise.
Speech patterns are often influenced by racial or ethnic
background as well as by occupation or schooling. In
general, however, the absence of obvious delusions,
hallucinations, or thought disorders together with the
presence of insight, good judgment, and socially
appropriate appearance and behavior are considered
normal results. A normal numerical score for the
MMSE is between 28 and 30.

Abnormal results
Abnormal results for a mental status examination
include:


Any evidence of organic brain damage.



Evidence of thought disorders.



A mood or affect that is clearly inappropriate to its
context.



Thoughts of suicide.

GALE ENCYCLOPEDIA OF MEDICINE

Illusion—A false visual perception of an object that
others perceive correctly. A common example is
the number of sightings of ‘‘UFOs’’ that turn out to
be airplanes or weather balloons.
Obsession—Domination of thoughts or feelings by
a persistent idea, desire, or image.
Organic brain disorder—An organic brain disorder
refers to impaired brain function due to damage or
deterioration of brain tissue.



Disturbed speech patterns.



Dissociative symptoms.



Delusions or hallucinations.

A score below 27 on the MMSE usually indicates
an organic brain disorder.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Neurologic Disorders: Neurologic Examination.’’ In
The Merck Manual of Diagnosis and Therapy.
2423

Mental status examination

abuse, rape, or other severe emotional traumas in adult
life. The examiner should also include information
about the patient’s occupation, level of education,
marital status, and right- or left-handedness.
Information about occupation and education helps
in evaluating the patient’s use of language, extent of
memory loss, reasoning ability, and similar functions.
Handedness is important in determining which half of
the patient’s brain is involved in writing, picking up a
pencil, or other similar tasks that he or she may be
asked to perform during the examination.

Mesothelioma

Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Eisendrath, Stuart J., MD, and Jonathan E. Lichtmacher,
MD. ‘‘Psychiatric Disorders: Psychiatric Assessment.’’
In Current Medical Diagnosis & Treatment 2001, edited
by L. M. Tierney, Jr., MD, et al., 40th ed. New York:
Lange Medical Books/McGraw-Hill, 2001.

Rebecca J. Frey, PhD

Mesothelioma
Definition
Mesothelioma is an uncommon disease that
causes malignant cancer cells to form within the lining
of the chest, abdomen, or around the heart. Its primary cause is believed to be exposure to asbestos.

Description
Malignant mesothelioma is also known as asbestos cancer or simply ‘‘meso.’’ Mesothelioma causes
cancerous cells to develop in the body’s mesothelium,
where they can spread to and damage vital organs and
tissue. These malignant cells can also metastasize to
other regions of the body. Mesothelioma is very difficult to diagnose and responds poorly to most treatment modalities, accounting for a poor prognosis.
The disease derives its name from the mesothelium, a sac-like membrane that protects most of the
body’s internal organs. It is divided into two distinct
protective layers of cells: the visceral (the layer directly
surrounding the organ) and the parietal (a sac around
the body cavity). By releasing a lubricating fluid, the
mesothelium allows the organs to move more freely
within the body cavity; for example, the contraction
and expansion of the lungs. The mesothelium is also
referred to according to where it is located in the body:
pleura (chest), peritoneum (abdomen), and pericardium (heart).
Over two-thirds of all mesothelioma cases begin in
the pleura region. Pleural mesothelioma spreads
through the chest cavity, occasionally developing in
the lungs as well. The disease most commonly causes
pleural effusion, an excess build-up of fluid inside the
chest cavity. This excess fluid increases pressure on the
lungs and restricts breathing. In addition, malignant
cells can cause the pleural lining to thicken and restrict
the breathing space even further.
2424

Peritoneal mesothelioma is the second most common form of the disease, accounting for less than 30%
of all cases. Malignant cells form in the peritoneum,
affecting the abdomen, bowel, liver, and spleen. Similar
to pleural mesothelioma, the disease also causes a build
up of excess fluid in the abdominal cavity. Normal
bodily functions, such as digestion, can be hindered
by the obstruction of organ movement.
Very rare forms of mesothelioma occur in the
pericardium, as well as the mesothelium of the male
and female reproductive organs. Cystic mesothelioma
of the peritoneum, another rare form of the disease,
occurs predominantly in women and is more benign in
nature.
Malignant mesothelioma takes the form of one of
three cell-types: epithelioid (50% to 70% of cases),
sarcomatous (7% to 20% of cases), and biphasic/
mixed (20% to 35% of cases). Of these cell-types,
epithelioid mesothelioma carries the most favorable
prognosis, followed by biphasic, and finally sarcomatous (very aggressive).
Mesothelioma remains relatively uncommon in
the United States, with approximately 2,500 new
cases reported annually. The incidence rates are
much higher in Western Europe (over 5,000 cases
reported annually). These numbers are expended to
climb dramatically over the next 20 years. Older males
(median age 60 at diagnosis) are three to five times
more likely to develop mesothelioma than women.
This is most like do to male predominance in those
professions with an increased risk of asbestos
exposure.

Causes & symptoms
Approximately 80% of all mesothelioma patients
have a history of asbestos exposure. The majority of
these patients were employed in an industry that
involved the use of asbestos in some fashion. In addition to occupational exposure, household exposure of
family members is not uncommon. An exposed individual can carry the asbestos particles on their clothing, skin, and in their hair when they return home,
resulting in paraoccupational exposure. Even brief
exposure to asbestos, as little as one to two months,
can result in long-term consequences. Although the
dangers of asbestos have been known for decades,
the long latency period of mesothelioma (30 to 40
years) means that majority of patients were already
exposed as far back as the 1950s. It is estimated that
up to eight million Americans have already been
exposed. Several industries, in particular, show a
higher incidence of asbestos exposure:
GALE ENCYCLOPEDIA OF MEDICINE

Insulators (Asbestos workers)



Boilermakers



Ship-fitters



Steel workers



Maintenance workers



Plumbers



Brake mechanics
Symptoms

Mesothelioma is very aggressive once it truly
takes hold. However, its initial symptoms are generally non-specific in nature and/or mimic other conditions, such as persistent pneumonia or gastronomical
disorders. Some patients will exhibit no symptoms at
all. As such, proper evaluation and diagnosis are commonly delayed and must be confirmed by a doctor.
Patients suffering from pleural mesothelioma most
commonly exhibit signs of dyspnea, pleural effusions,
and/or chest pain. The majority of pleural effusion
symptoms will exhibit in the right lung (60% of the
time). Patients may also exhibit persistent cough, weight
loss, weakness, fever, and difficulty swallowing.
Patients suffering from peritoneal mesothelioma
most commonly exhibit signs of pain and/or swelling
in the abdomen from fluid retention or tumor growth.
Weight loss, nausea, bowel obstruction, anemia, fever,
and swelling in the legs and/or feet are also known
symptoms.

conducted in a hospital setting. Both procedures
involve a fiber-optic imaging tool being inserted into
the patient through an incision. These endoscopic
tools will provide the doctor with a closer look at the
body cavity, and any abnormal tissue or fluid build-up
found therein. Excess fluid can be suctioned out
through a needle or tube, in a process known as thoracentesis (for the chest) or paracentesis (for the abdomen). Additionally, the doctor may perform a biopsy
of any abnormal tissue they discover during this time.
Pathological examination of abnormal tissue, as well
as fluid, remains the only effective method of confirming the diagnosis of mesothelioma. Biopsy will also
assist the doctor in properly staging the disease’s
progression.
Once a confirmation of malignant mesothelioma
has been established, the doctor will conduct further
tests to determine the extent to which the primary
disease has spread. This diagnostic process is known
as ‘‘staging.’’ Malignant pleural mesothelioma of can
be broken into four stages:


Localized Malignant Mesothelioma (Stage 1)—
Cancer is present in the right or left pleura. May
involve the lung, the pericardium, or diaphragm on
that side.



Advanced Malignant Mesothelioma (Stage 2)—
Cancer has spread beyond the right or left pleura to
lymph nodes on that side. May involve the lung, the
pericardium, or diaphragm on that side.



Advanced Malignant Mesothelioma (Stage 3)—
Cancer has spread into the chest wall, diaphragm,
ribs, heart, esophagus, or through the abdominal
lining. Nearby lymph nodes may or may not be
involved.



Advanced Malignant Mesothelioma (Stage 4)—
Cancer shows evidence of metastasis or spread through
the bloodstream to distant organs and/or tissues.

Diagnosis
Only a physician can properly diagnose mesothelioma. A review of the patient’s medical history,
including any past exposure to asbestos, should be
conducted for any patient displaying dyspnea, chest
pain, fluid build-up, or pain and/or swelling in the
abdomen. This review is followed up with a complete
physical examination, which should involve the use of
imaging techniques. X rays, computed tomography
(CT) scans, and magnetic resonance (MRI) scans of
the chest and/or abdomen, as well as lung function,
can provide the doctor with critical diagnostic information. Although positron emission tomography scans
are expensive and not covered under most insurance,
this diagnostic tool has proven very useful in determining tumor sites and staging of the disease.
If indicated, the doctor may wish to internally
examine the patient’s chest and/or abdominal cavity.
These diagnostic procedures, known as thoracoscopy
(chest) and peritoneoscopy (abdomen), are usually
GALE ENCYCLOPEDIA OF MEDICINE

Recurrent malignant mesothelioma may also
occur, where the cancer returns in its original location
or elsewhere in the body even after treatment.

Treatment
There are three traditional treatment modalities
for mesothelioma: surgery, radiation therapy, and chemotherapy. The location and the stage of the disease,
as well as the patient’s age and general health, will
determine which treatment should be utilized.
Additionally, these modalities can be combined if indicated. Indeed, the multimodality approach appears to
provide the most positive results for treating
mesothelioma.
2425

Mesothelioma



Mesothelioma

Surgery, the most common treatment, involves
the removal of the tumor. In the early stages of
mesothelioma, this only involves removal of a section
of the mesothelium and surrounding tissue, but may
require removing part of the diaphragm as well. For
more advanced stages of the disease, removing the
entire lung may be the only option, which is known
as pneumonectomy.
Radiation therapy, also known as radiotherapy,
destroys and shrinks the cancer cells through various
types of radiation. Both external (such as a machine)
and internal (such as radioisotopes) radiation therapies can be utilized effectively to treat malignant
mesothelioma.
Finally, chemotherapy, a systemic treatment
modality, uses anticancer drugs to destroy the cancerous cells throughout the body. The majority of drugs
used to treat mesothelioma are delivered intravenously. The effectiveness of intracavitary chemotherapy, the process of directly injecting the drugs into the
chest or abdominal cavity, is being studied.
Pain and other symptoms caused by fluid build-up
around the chest and/or abdomen can be treated by
drain excess fluid through a needle or tube. These procedures are known as thoracentesis (chest) and paracentesis (abdomen). Drugs, radiotherapy, and surgery
can also relieve or prevent further fluid accumulation.
Physicians are currently studying other treatment
modalities, such as immunotherapy, gene therapy, and
intraoperative photodynamic therapy.

Alternative treatment
Due to the poor prognosis associated with mesothelioma, regardless of proper treatment, in many cases
palliative care is the preferred, and only, option available
to patients. This is particularly true for the advanced
stages of the disease. By treating the symptoms rather
than the disease itself, the goal of this approach is to
obtain ‘‘quality’’ of life instead of ‘‘quantity’’ of life.
Palliative care aims to relieve the patient s discomfort
caused by dyspnea and pain. Chemotherapy, radiation,
and/or surgical pleurodeis, in combination with effective
management of pain and respiratory function should
form the basis of proper palliative care of mesothelioma.
Techniques to reduce stress, such as acupuncture, aromatherapy, massage, and reflexology, can provide addition benefit to the patient’s sense of well-being.

Prognosis
The stage and location, what cell-type is involved,
as well as the patient’s age and histology factor greatly
2426

KEY TERMS
Asbestos—A naturally occurring mineral, utilized
worldwide for its durability and heat resistant qualities. Extremely fibrous in nature, asbestos particles
can easily enter the respiratory system and damage
sensitive tissue. This damage can result in asbestosis, mesothelioma, and lung cancer.
Dyspnea—A difficulty in breathing or shortness of
breath, typically associated with some form of heart
or lung disease. Also known as air hunger.
Mesothelium—A membrane/sac that that protects
the body’s major internal organs and allows them
freedom of movement (for example, lung contractions). The mesothelium is comprised of several
regions, including the abdominal cavity (peritoneum),
the chest cavity (pleura), and pericardium (heart).
Pleural effusion—An abnormal accumulation of
fluid in the pleura, a fibrous membrane that lines
the inside of the chest cavity and protects the lungs.
This accumulation can cause shortness of breath,
cough, and chest pain.

on life expectancy. Unfortunately, even with aggressive
treatment, the prognosis for mesothelioma patients is
poor. Pleural mesothelioma offers a median survival
time of approximately 16 to 17 months after initial
symptoms. Prognosis for peritoneal mesothelioma is
poorer and has a median survival time of only ten
months after initial symptoms. Unfortunately, the
more advanced stages of mesothelioma may offer as
little as four or five month’s survival time.
The survival time for patients with localized
mesothelioma can be extended several months with
aggressive therapy, with roughly 20% of patients surviving past the five-year mark. Therapy programs recently
developed at leading cancer centers have extended this
survival time even further. Dr. Sugarbaker, of the
Brigham and Women’s Center in Boston, has achieved
a median of 40% survival rate at five years with his
treatment regimen for pleural mesothelioma, as
reported in the Journal of Thoracic and Cardiovascular
Surgery. Other programs are also exhibiting favorable
results. However, despite such successes, no cure for
mesothelioma currently exists.

Prevention
Avoiding or limiting exposure to asbestos is the
best way to prevent mesothelioma. Unfortunately,
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Jaurand, Marie-Claude, and Jean Bignon (eds). The
Mesothelial Cell and Mesothelioma. New York: Marcel
Dekker, 1994.
Robinson, Bruce, and A. Philippe Chahinian (eds).
Mesothelioma. London: Martin Dunitz, 2002.
PERIODICALS

Pistolesi, Massimo, and James Rusthoven. ‘‘Malignant
Pleural Mesothelioma.’’Chest 126 (October, 2004):
1318-1329
Sugarbaker, David, et al. ‘‘Resection Margins, Extrapleural
Nodal Status, and Cell Type Determine Postoperative
Long-Term Survival in Trimodality Therapy of
Malignant Pleural Mesothelioma.’’Journal of Thoracic
and Cardiovascular Surgery 117 (January, 1999): 54-65
van Ruth, Serge, Paul Baas, and Frans Zoetmulder.
‘‘Surgical Treatment of Malignant Pleural
Mesothelioma.’’ Chest 123 (February, 2003): 551-561
ORGANIZATIONS

Mesothelioma Research Foundation of America. 5716
Corsa Ave., Suite 203, Westlake Village, CA 91362.
(800) 281-9804. <http://www.mesothelioma-rfa.org>.
The Mesothelioma Center. 1030 Fifth Ave., Pittsburgh, PA
15219. (412) 471-3980. <http://
mesotheliomacenter.org>.
OTHER

‘‘Malignant Mesothelioma.’’ National Cancer
Institute<http://www.nci.nih.gov/cancertopics/types/
malignantmesothelioma/>.
‘‘Mesothelioma.’’Mesothelioma Information<http://
www.mesoinfo.com>.
‘‘Mesothelioma.’’Mesothelioma Web<http://
www.mesotheliomaweb.org>.

Jason Fryer

Metabolic acidosis
Definition
Metabolic acidosis is a pH imbalance in which the
body has accumulated too much acid and does not
have enough bicarbonate to effectively neutralize the
effects of the acid.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Metabolic acidosis, as a disruption of the body’s
acid/base balance, can be a mild symptom brought on
by a lack of insulin, a starvation diet, or a gastrointestinal disorder like vomiting and diarrhea. Metabolic
acidosis can indicate a more serious problem with a
major organ like the liver, heart, or kidneys. It can also
be one of the first signs of drug overdose or poisoning.

Causes and symptoms
Metabolic acidosis occurs when the body has
more acid than base in it. Chemists use the term
‘‘pH’’ to describe how acidic or basic a substance is.
Based on a scale of 14, a pH of 7.0 is neutral. A pH
below 7.0 is an acid; the lower the number, the stronger the acid. A pH above 7.0 is a base; the higher the
number, the stronger the base. Blood pH is slightly
basic (alkaline), with a normal range of 7.36-7.44.
Acid is a natural by-product of the breakdown of
fats and other processes in the body; however, in
some conditions, the body does not have enough
bicarbonate, an acid neutralizer, to balance the
acids produced. This can occur when the body uses
fats for energy instead of carbohydrates. Conditions
where metabolic acidosis can occur include chronic
alcoholism, malnutrition, and diabetic ketoacidosis.
Consuming a diet low in carbohydrates and high in
fats can also produce metabolic acidosis. The disorder may also be a symptom of another condition like
kidney failure, liver failure, or severe diarrhea. The
build up of lactic acid in the blood due to such conditions as heart failure, shock, or cancer, induces
metabolic acidosis. Some poisonings and overdoses
(aspirin, methanol, or ethylene glycol) also produce
symptoms of metabolic acidosis.
In mild cases of metabolic acidosis, symptoms
include headache, lack of energy, and sleepiness.
Breathing may become fast and shallow. Nausea,
vomiting, diarrhea, dehydration, and loss of appetite
are also associated with metabolic acidosis. Diabetic
patients with symptoms of metabolic acidosis may
also have breath that smells fruity. The patient may
lose consciousness or become disoriented. Severe cases
can produce coma and death.

Diagnosis
Metabolic acidosis is suspected based on symptoms, but is usually confirmed by laboratory tests
on blood and urine samples. Blood pH below 7.35
confirms the condition. Levels of other blood components, including potassium, glucose, ketones, or lactic
2427

Metabolic acidosis

because of the significant delay between exposure and
onset (30 to 40 years), it is probably too late to prevent
the development of mesothelioma for most patients.
Not smoking may slow the disease’s progression and/
or prevent other further complications associated with
asbestos exposure.

Metabolic alkalosis

KEY TERMS
Diabetic ketoacidosis—A condition caused by low
insulin levels where the amount of sugar and
ketones in the blood is high.
pH—A measurement of the acidity or alkalinity of a
solution based on the amount of hydrogen ions
available. Based on a scale of 14, a pH of 7.0 is
neutral. A pH below 7.0 is an acid; the lower the
number, the stronger the acid. A pH above 7.0 is a
base; the higher the number, the stronger the base.
Blood pH is slightly alkaline (basic) with a normal
range of 7.36-7.44.

dehydration or the accumulation of ketones or lactic
acid.
Resources
BOOKS

‘‘Fluid, Electrolyte, and Acid-Base Disorders.’’ In Family
Medicine Principles and Practices. 5th ed. New York:
Springer-Verlag, 1998.

Altha Roberts Edgren

Metabolic alkalosis
acid, may also be above normal ranges. The level of
bicarbonate in the blood will be low, usually less than
22 mEq/L. Urine pH may fall below 4.5 in metabolic
acidosis.

Treatment
Treatment focuses first on correcting the acid
imbalance. Usually, sodium bicarbonate and fluids
will be injected into the blood through a vein. An
intravenous line may be started to administer fluids
and allow for the quick injection of other drugs
that may be needed. If the patient is diabetic, insulin
may be administered. Drugs to regulate blood pressure or heart rate, to prevent seizures, or to control
nausea and vomiting might be given. Vital signs like
pulse, respiration, blood pressure, and body temperature will be monitored. The underlying cause of
the metabolic acidosis must also be diagnosed and
corrected.

Prognosis
If the metabolic acidosis is recognized and treated
promptly, the patient may have no long-term complications, however, the underlying condition that
caused the acidosis needs to be corrected or managed.
Severe metabolic acidosis that is left untreated will
lead to coma and death.

Prevention
Diabetic patients need to routinely test their urine
for sugar and acetone, strictly follow their appropriate
diet, and take any medications or insulin to prevent
metabolic acidosis. Patients receiving tube feedings or
intravenous feedings must be monitored to prevent
2428

Definition
Metabolic alkalosis is a pH imbalance in which
the body has accumulated too much of an alkaline
substance, such as bicarbonate, and does not have
enough acid to effectively neutralize the effects of the
alkali.

Description
Metabolic alkalosis, as a disturbance of the body’s
acid/base balance, can be a mild condition, brought on
by vomiting, the use of steroids or diuretic drugs, or the
overuse of antacids or laxatives. Metabolic alkalosis
can also indicate a more serious problem with a major
organ such as the kidneys.

Causes and symptoms
Metabolic alkalosis occurs when the body has
more base than acid in the system. Chemists use the
term ‘‘pH’’ to decribe how acidic or alkaline (also
called basic) a substance is. Based on a scale of 14, a
pH of 7.0 is neutral. A pH below 7.0 is an acid; the
lower the number, the stronger the acid. A pH above
7.0 is alkaline; the higher the number, the stronger the
alkali. Blood pH is slightly alkaline, with a normal
range of 7.36-7.44. Conditions that lead to a reduced
amount of fluid in the body, like vomiting or excessive
urination due to use of diuretic drugs, change the
balance of fluids and salts. The blood levels of potassium and sodium can decrease dramatically, causing
symptoms of metabolic alkalosis.
In cases of metabolic alkalosis, slowed breathing
may be an initial symptom. The patient may have
episodes of apnea (not breathing) that may go on 15
seconds or longer. Cyanosis, a bluish or purplish discoloration of the skin, may also develop as a sign of
GALE ENCYCLOPEDIA OF MEDICINE

pH—A measurement of the acidity or alkalinity of a
solution based on the amount of hydrogen ions
available. Based on a scale of 14, a pH of 7.0 is
neutral. A pH below 7.0 is an acid; the lower the
number, the stronger the acid. A pH above 7.0 is a
base; the higher the number, the stronger the base.
Blood pH is slightly alkaline (basic) with a normal
range of 7.36-7.44.

Severe metabolic alkalosis that is left untreated will
lead to convulsions, heart failure, and coma.

Prevention
Patients receiving tube feedings or intravenous
feedings must be monitored to prevent an imbalance
of fluids and salts, particularly potassium, sodium,
and chloride. Overuse of some drugs, including diuretics, laxatives, and antacids, should be avoided.
Resources
BOOKS

inadequate oxygen intake. Nausea, vomiting, and
diarrhea may also occur. Other symptoms can include
irritability, twitching, confusion, and picking at bedclothes. Rapid heart rate, irregular heart beats, and a
drop in blood pressure are also symptoms. Severe
cases can lead to convulsions and coma.

Diagnosis
Metabolic alkalosis may be suspected based on
symptoms, but often may not be noticeable. The condition is usually confirmed by laboratory tests on
blood and urine samples. Blood pH above 7.45 confirms the condition. Levels of other blood components, including salts like potassium, sodium, and
chloride, fall below normal ranges. The level of bicarbonate in the blood will be high, usually greater than
29 mEq/L. Urine pH may rise to about 7.0 in metabolic alkalosis.

Treatment
Treatment focuses first on correcting the imbalance. An intravenous line may be started to administer
fluids (generally normal saline, a salt water solution)
and allow for the quick injection of other drugs that
may be needed. Potassium chloride will be administered. Drugs to regulate blood pressure or heart rate,
or to control nausea and vomiting might be given. Vital
signs like pulse, respiration, blood pressure, and body
temperature will be monitored. The underlying cause
of the metabolic alkalosis must also be diagnosed and
corrected.

Prognosis
If metabolic alkalosis is recognized and treated
promptly, the patient may have no long-term complications; however, the underlying condition that
caused the alkalosis needs to be corrected or managed.
GALE ENCYCLOPEDIA OF MEDICINE

Bennett, J. Claude, and Fred Plum, eds. ‘‘Acid-Base
Disturbances.’’ In Cecil Textbook of Medicine.
Philadelphia: W. B. Saunders Co., 1996.
DuBose, Thomas D., Jr. ‘‘Acidosis and Alkalosis’’ In
Harrison’s Principles of Internal Medicine, ed. Anthony
S. Fauci, et al. New York: McGraw-Hill, 1997.
‘‘Fluid, Electrolyte, and Acid-Base Disorders.’’ In Family
Medicine Principles and Practices. 5th ed. New York:
Springer-Verlag, 1998.
‘‘Fluid & Electrolyte Disorders.’’ In Current Medical
Diagnosis and Treatment, 1998. 37th ed. Ed. Stephen
McPhee, et al. Stamford: Appleton & Lange, 1997.

Altha Roberts Edgren

Metabolic encephalopahty see Delirium
Meth see Muscle relaxants

Methadone
Definition
Methadone is a powerful narcotic drug in the
same class as heroin. This class is known as the
opioids.

Purpose
Methadone, formerly known as dolophine, is a
psycho-active drug, meaning that it affects the mind
or behavior. It belongs to the class of opioids, drugs
that share some of the analgesic properties, and mimic
the action of some of the body’s naturally occurring
chemicals called peptides, such as endorphins and
enkephalines.
Methadone is used to relieve chronic pain in cancer patients and as a maintenance drug to control
withdrawal symptoms in people undergoing treatment
for opiate addiction.
2429

Methadone

KEY TERMS

Methadone

In opiate addiction treatment, methadone blocks
the opioid receptors of the brain that bind opiates such
as heroin. The blocking of these receptors leads to two
major effects:




because these chemical receptors remain blocked by
methadone for up to 24 hours, even if a person
addicted to heroin takes heroin after the administration of methadone, this person is not likely to feel the
same effects of the heroin as he or she previously felt;
because the action of methadone is associated with
slower and less intense withdrawal symptoms than
those of heroin, the patient can experience milder
opiate effects while the addiction is being treated
and avoid the unpleasant withdrawal symptoms
associated with heroin.

Methadone has also been shown to reduce cravings for heroin while not altering a person’s mood.

Precautions
Methadone magnifies the effects of alcohol and
other central nervous system depressants, such as antihistamines, cold medicines, sedatives, tranquilizers,
other prescription and over-the-counter (OTC) pain
medications, barbiturates, seizure medications, muscle
relaxants, and certain anesthetics including some dental anesthetics. Alcohol and other central nervous system depressants should not be taken or consumed
while methadone is being taken.
Methadone is a powerful narcotic. It can cause
some people to feel drowsy, dizzy, or light-headed.
People taking methadone should not drive a car or
operate machinery.
Intentional or accidental overdose of methadone
can lead to unconsciousness, coma, or death. The signs
of methadone overdose include confusion, difficulty
speaking, seizures, severe nervousness or restlessness,
severe dizziness, severe drowsiness, and/or slow or
troubled breathing. These symptoms are increased by
alcohol or other central nervous system (CNS) depressants. Anyone who feels that he or she, or someone
else, may have overdosed on methadone, or a combination of methadone and other central nervous system
depressants, should seek emergency medical attention
for that person at once.

Description
A typical adult dosage for methadone is 5–20 mg
as an oral solution, 2.5–10 mg as an oral tablet or
injection, every four to eight hours as necessary for
pain. When used for detoxification, methadone is
2430

initially given in a dose of 15–100 mg per day as an
oral solution. This dose is then decreased until the
patient no longer requires the medication. The injection form of methadone is only used for detoxification
in patients who are unable to take the medication by
mouth.

Preparation
No preparation is generally necessary prior to the
intake of methadone as a pain reliever. In cases of
maintenance treatments, it is important to be sure
that the patient is not currently intoxicated by alcohol,
heroin, other opioids, or taking other central nervous
system depressants.

Aftercare
Patients receiving methadone should be monitored for adverse reactions to this drug, and/or possible accidental overdose.

Risks
Methadone can interfere with or exacerbate certain medical conditions. For these reasons, it is important that the prescribing physician be informed of any
current case, or history of:


alcohol abuse



brain disease or head injury



colitis



drug dependency, particularly of narcotics



emotional problems



emphysema, asthma, or other chronic lung disease



enlarged prostate



gallstones or gallbladder disease



heart disease



kidney disease



liver disease



problems with urination



seizures



underactive thyroid

Side effects
The most common side effects of methadone
include:


constipation



dizziness
GALE ENCYCLOPEDIA OF MEDICINE

drowsiness



itching



nausea

Analgesic—Any agent that relieves pain.



urine retention



vomiting

Central nervous system (CNS) depressant—Any
drug that tends to reduce the activity of the central
nervous system. The major drug categories
included in this classification are: alcohol, anesthetics, anti-anxiety medications, antihistamines,
antipsychotics, hypnotics, narcotics, sedatives,
and tranquilizers.
Endorphins—Any of several opiate peptides naturally produced in the brain that bind to certain neuron receptors and have the effect of relieving pain.

Less common side effects of methadone include:


abnormally fast or slow heartbeat



blurred or double vision



cold, clammy skin



depression or other mood changes



dry mouth



fainting



hallucinations



hives



loss of appetite



nightmares or unusual dreams



pinpoint pupils of the eyes



redness or flushing of the face



restlessness



rigid muscles



ringing or buzzing in the ears



seizure



severe drowsiness



skin reaction at the site of injection



stomach cramps or pain



sweating



trouble sleeping (insomnia)



yellowing of the skin or whites of the eyes

Normal results
Normal results after the administration of methadone to treat chronic pain is the alleviation of that
patient’s pain, at least to the point where the pain is
bearable.
Normal results of methadone treatment to control
heroin addiction, is that the patient reduces heroin
intake almost immediately upon starting methadone
treatments, followed by complete abstinence, usually
within two weeks after starting treatment.
GALE ENCYCLOPEDIA OF MEDICINE

Methadone



KEY TERMS

Enkephalines—Peptide produced by the body that
have analgesic properties.
Morphine—Morphine is the naturally occurring
opioid in the opium poppy, Papaver somniferum. It
is a powerful narcotic analgesic, and its primary clinical use is in the management of moderately severe to
severe pain. After heroin, morphine has the greatest
potential for addiction of all narcotic analgesics.
Narcotic—Any drug that produces insensibility or
stupor and/or generally causes effects similar to
those caused by morphine.
Opiate—Any narcotic analgesic derived from a
natural source, such as morphine from the opium
poppy.
Opioid receptors—Receptors located in the brain
and various organs that bind opiates or opioid
substances.
Opioids—One of the major classes of semi or fully
synthetic psycho-active drugs that includes
methadone.
Psychoactive drugs—Any drug that affects the mind
or behavior. There are five main classes of psychoactive drugs: opiates and opioids (e.g. heroin
and methadone); stimulants (e.g. cocaine, nicotine),
depressants (e.g. tranquilizers, antipsychotics, alcohol), hallucinogens (e.g. LSD), and marijuana and
hashish.
Receptor—A molecular structure on the surface
that selectively binds a specific substance resulting
in a specific physiological effect.

Resources
PERIODICALS

Sadovsky, Richard. ‘‘Methadone Maintenance Therapy.’’
American Family Physician July 15, 2000.

2431

Methemoglobinemia

ORGANIZATIONS

National Alliance of Methadone Advocates (NAMA). 435
Second Avenue, New York, NY, 10010. (212) 595-6262.
<http://www.methadone.org/>.
National Clearinghouse for Alcohol and Drug Information.
11426-28 Rockville Pike, Suite 200, Rockville, MD
20852. (800) 729-6686. <http://www.health.org/>.

Paul A. Johnson, Ed.M.



Cyanosis unaffected by oxygen administration



Blood that is dark or chocolate in color that will not
change to red in the presence of oxygen



Headache



Weakness



Confusion



Chest pain

When methemoglobin levels are above 70% death
may result if not treated immediately.

Methemoglobinemia
Definition
When excessive hemoglobin in the blood is converted to another chemical that cannot deliver oxygen
to tissues, called methemoglobin.

Diagnosis
Diagnosis is based on the symptoms and history.
If these are indicative of methemoglobinemia blood
tests are performed to confirm the presence and level
of methemoglobin.

Treatment
Description
The molecule hemoglobin in the blood is responsible for binding oxygen to give to the body. When
hemoglobin is oxidized to methemoglobin its structure
changes and it is no longer able to bind oxygen.
Hemoglobin is constantly under oxidizing stresses:
however, normally less than 1% of a person’s hemoglobin is in the methemoglobin state. This is due to the
body’s systems that reduce methemoglobin back to
hemoglobin. Infants have a higher risk of acquiring
methemoglobinemia because infant hemoglobin is
more prone to be oxidized to methemoglobin.

Causes and symptoms
Methemoglobinemia can either be congenital or
acquired.
There are two causes of the congenital form. One
cause is a defect in the body’s systems to reduce methemoglobin to hemoglobin. The other cause is a mutant
form of hemoglobin called hemoglobin M that cannot
bind to oxygen. Both of these forms are typically
benign.
Acquired methemoglobinemia is caused by an
external source, usually a drug or medication. Some
of these medications include benzocaine, lidocaine and
prilocaine. These medications can inhibit the body’s
systems of reducing methemoglobin to hemoglobin
resulting in methemoglobinemia.
With a methemoglobin level of 3-15% skin can
turn to a pale gray or blue (cyanosis). With levels
above 25% the following symptoms may be present:
2432

For acquired methemoglobinemia the typical
treatment is with methylene blue. This is administered
with an IV over a five-minute period and results are
typically seen within 20 minutes. Methylene blue
reduces methemoglobin back to hemoglobin.
Though congenital methemoglobinemia is usually
benign, the form due to a defective reducing system
can be treated with ascorbic acid (vitamin C) taken
daily. The other congenital form due to hemoglobin M
has no treatment as of late.

Alternative treatment
There are not any known alternative treatments
for methemoglobinemia. Methylene blue, or a similar
treatment, is needed to reduce methemoglobin to
hemoglobin.

Prognosis
If found early, acquired methemoglobinemia can
be easily treated with no side effects. After treatment
with methylene blue the patient can expect a full
recovery.
Congenital methemoglobinemia is typically
benign and should be observed. If methemoglobinemia symptoms occur the person should be taken to the
hospital for treatment.

Prevention
If a person gets methemoglobinemia from a certain medication that medication should be avoided at
GALE ENCYCLOPEDIA OF MEDICINE

Cyanosis—When the body does not receive
enough oxygen.
Oxidation—When a chemical element or compound loses an electron.
Reduction—When a chemical element or compound gains an electron.

all costs in the future. For people with congenital
methemoglobinemia medications or other things that
are known to oxidize hemoglobin should be avoided.
Resources
BOOKS

Beutler, Ernest. ‘‘Methemoglobinemia and Other Causes of
Cyanois.’’ In Williams Hematology. 6th ed. New York:
McGraw-Hill, 2001, pp. 611-17.
PERIODICALS

Wilburn-Goo, Dawn, and Lloyd. ‘‘When Patients Become
Cyanotic: Acquired Methemoglobinemia.’’ Journal of
the American Dental Association June 1999: 826-31.
Wright, Lewander, and Woolf. ‘‘Methemoglobinemia:
Etiology, Pharmacology, and Clinical Management.’’
Annals of Emergency Medicine November 1999: 646-56.
OTHER

eMedicine. Website. 2001. <http://www.emedicine.com>.

Thomas Scott Eagan
Ronald Watson, PhD

Methylphenidate see Central nervous system
stimulants
Metoprolol see Beta blockers

Anophthalmia is caused by a defect in embryonic
development. The total absence of an eye is extremely
rare and often a clinical sign associated with a broad
range of genetic disorders or, more commonly, a
sporadic mutation. Sporadic transmission occurs in
the affected individual due to a genetic abnormality.
It is not passed on from the parents, but usually due to
a combination of environmental and genetic influences. More commonly anophthalmia clinically presents as a small cyst. The defect, which causes
anophthalmia, is an absence of the optic vesicle, a
structure important for eye development. The genetic
abnormality usually occurs during weeks one to three
after conception. It is estimated that the incidence of
microphthalmia occurs 0.22 times per 1,000 live births.
Anophthalmia can occur during adult life but not
associated with a genetic cause.
Microphthalmia refers to an abnormally small
eye. This clinical sign is often associated with autosomal dominant or recessively transmitted genetic disorders. Most disorders dominantly inherited with
microphthalmia are associated with some visual capabilities in infancy and early childhood.
Microphthalmia may be isolated (the only presenting
sign) or associated with a range of ocular or systemic
abnormalities. Isolated cases of microphthalmia may
be sporadic or inherited. There is a variable degree of
visual impairment. Microphthalmia occurs due to
autosomal recessive transmission and is part of a syndrome associated with abnormalities in the retina or
systemic lesions. Microphthalmia results from a developmental defect after formation of the optic vesicle.
The developmental abnormality causes the optic vesicle to fold inwards, resulting in the formation of a cyst.
The cyst will progressively swell from birth, and it may
be situated along the optic nerve. The cyst may also be
situated along other important eye structures.

Metronidazole see Antiprotozoal drugs
Micronaz see Antifungal drugs, topical

Microphthalmia and
anophthalmia
Definition
Anophthalmia is the complete absence of an eye.
Microphthalmia is an eye that has an abnormal
smallness.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Microphthalmia and anophthalmia can be caused
by sporadic or genetic mutations. Anophthalmia is
characterized by a total absence of an eye.
Anophthalmia in an adult is usually caused by trauma,
infection, tumor, or advanced eye disease.

Diagnosis
Microscope examination confirms the diagnosis
of true anophthalmia. The clinician examines a piece
of tissue taken from the eye and notes eviscerated
tissue. For microphthalmia the confirmation can be
2433

Microphthalmia and anophthalmia

Description

KEY TERMS

Mifepristone

ORGANIZATIONS

KEY TERMS
Axial—A straight line passing through a spherical
body between its two poles and about which the
body may revolve.
Eviserated—Removal of eye contents.
Prostheses—A synthetic object that resembles a
missing anatomical part.
Retina—A major portion of the eye responsible for
reception of visual light rays.

established by eye measurements. Eyes, which have an
axial length <21 mm in an adult, or <19 mm in a oneyear-old
child
are
described
as
having
microphthalmia.

Treatment
Large cysts causing microphthalmia should be
aspirated or removed surgically. There is no known
cure for anophthalmia or microphthalmia. For
anophthalmia a prosthetic eye can be fitted which
may involve surgery. Treatment for microphthalmia
depends on the complexity of eye involvement.

Prognosis
For anophthalmia, prosthetic eyes should be seen
by a specialist two to three times per year to assess fit,
mobility, and smoothness. They are usually well tolerated and have good appearance and mobility. The
clinical course for microphthalmia depends on the
extent of smallness, but usually patients progress
favorably without major treatment. Since the smallness is distinctly noticeable, there may be individual
cosmetic considerations.

Prevention
There is no known prevention for either, since
these clinical signs are commonly associated with
genetic inheritance.
Resources
BOOKS

Yanoff, Myron, et al, editors. Ophthalmology. 1st ed. Mosby
International Ltd., 1999.
PERIODICALS

Mills, M. ‘‘The Eye in Childhood.’’ American Family
Physician 60 (September 1999).
2434

American Society of Human Genetics. Administrative
Office. 9650 Rockville Pike Bethesda, Maryland 208143998. (301) 571-1825. 2001. <http://www.faseb.org/
genetics/ashg/moreinfo.htm>.

Laith Farid Gulli, M.D.

Middle ear infection see Otitis media
Mifeprex see Mifepristone

Mifepristone
Definition
Mifepristone is a pill that can be taken as an
alternative to a surgical abortion.

Purpose
This medication most often is used for ending
early pregnancies. In 2003, studies were surfacing
reporting other possible uses for mifepristone, at
least at low doses. These studies included its possible
use in treating psychotic depression. Low-dose mifepristone also showed success as a treatment for uterine
fibroids, or benign growths in the muscular tissue of a
woman’s uterus. However, many uses of the drug
other than for abortions were still experimental, even
if promising.
Mifespristone’s primary use for medical abortions
is preferred by many over surgical approaches to abortions. It has emerged as a form of emergency contraception when taken at low does within a short time
period following possible conception.

Precautions
Women who are more than seven weeks pregnant
(or 49 days since their last menstrual period) should
not take mifepristone. Other reasons to avoid mifepristone include: use of an intrauterine device (IUD),
ectopic pregnancy, use of blood thinners, bleeding disorders, use of steroid medications, allergies to mifepristone or similar drugs and lack of access to medical
help within two weeks after the treatment. When the
drug is used at low doses as emergency contraception,
it poses few side effects.
GALE ENCYCLOPEDIA OF MEDICINE

Mifepristone, sold commercially under the name
Mifeprex, also is known as RU-486, the abortion pill,
the early option pill for medical abortion. While it has
been used for many years in Europe, mifepristone has
only been available for use in the United States since
the U.S. Food and Drug Administration (FDA)
approved it in 2000 for use in abortion. More than
37,000 abortions were performed using the pill in the
first six months of 2001.
This drug causes pregnancy to end by blocking the
female hormone progesterone. The lack of progesterone makes the uterus shed its lining, which causes
bleeding similar to a menstrual period. Three days
after taking mifepristone, women are given a second
drug, misprostol, to cause uterine contractions that
expel the contents of the uterus. Most women are
able remain in their own home while they pass the
fetus.

Preparation
Before taking mifepristone, health care providers
likely will give the woman a urine or blood test to be
sure that she is, in fact, pregnant. They also may give
her some counseling and support. Once she has made
the decision to use mifepristone, they will ask her to
sign a written statement that she has decided to end her
pregnancy.

Aftercare
Using mifepristone and misoprostol causes heavy
bleeding and cramping. Doctors can offer pain medicine, such as Motrin, to ease the cramps. For two
weeks after treatment with mifepristone, health care
providers likely will ask patients to abstain from sexual intercourse, heavy lifting and strenuous exercise.
They also may advise against breast-feeding, since
scientists are not sure if the drug is present in breast
milk.
Physicians require patients to come in for a follow-up visit 14 days after their first dose of mifepristone to verify that they are no longer pregnant and
that they are properly healing.

Risks
Other common side effects include: fatigue, headaches, dizziness, nausea, vomiting, diarrhea and lowback pain.
Since pregnancy hormones are in flux after a
medical abortion, many women have emotional
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Dilation and curettage (D and C)—During this
surgical procedure, a physician dilates the cervix,
then uses an instrument to scrape tissue away from
the walls of the uterus.
Misprostol—A drug used in combination with
mifepristone to cause uterine contractions that
expel the contents of the uterus.

side-effects, such as mood swings, depression or a
mild case of the blues. These feelings usually subside
when hormones stabilize a few weeks later. For those
who feel stuck in their grief or anger about the situation, counseling or support groups may offer relief.

Normal results
Most women feel better after about two weeks.
Bleeding and spotting usually occurs for 9-16 days, but
may last for a month.

Abnormal results
In some cases, mifepristone does not completely
end the pregnancy. If the fetus is still left inside the
uterus, a doctor may recommend a surgical abortion,
or a procedure called dilation and curettage (D and C).
About five to eight of every 100 women who take
mifepristone go on to have a surgical abortion,
according to the FDA. During a D and C, which
usually is done at a hospital or clinic under a local
anesthetic, a physician dilates the cervix, then uses an
instrument to scrape any residual tissue away from the
walls of the uterus. This allows the heavy bleeding to
eventually stop so a woman can return to her normal
cycle sooner.
Resources
PERIODICALS

‘‘Abortion Pills Account For 5% of U.S. Abortions.’’
Medical Letter on the CDC and FDA February 9,
2003: 7.
‘‘The Abortion Pill’s Grim Progress.’’ Mother Jones 24
(January 1, 1999).
Grimes, David A, Mitchell D. Creinin. ‘‘Induced Abortion:
an Overview for Internists.’’ Annals of Internal Medicine
April 20, 2004: 620–627.
‘‘Low-dose Mifepristone Blocks Pregnancy by Altering
Ovarian Function.’’ Drug Week March 5, 2004: 107.
‘‘Treatments for Depression with Psychosis.’’ Harvard
Mental Health Letter August 2003.
2435

Mifepristone

Description

Migraine headache

Walling, Anne D. ‘‘Low-dose Mifepristone Shrinks Uterine
Fibroids.’’ American Family Physician September 1,
2003: 956.

Melissa Knopper
Teresa G. Odle

Migraine headache
Definition
Migraine is a type of headache marked by severe
head pain lasting several hours or more.

Description
Migraine is an intense and often debilitating type
of headache. Migraines affect as many as 24 million
people in the United States, and are responsible for
billions of dollars in lost work, poor job performance,
and direct medical costs. Approximately 18% of
women and 6% of men experience at least one
migraine attack per year. More than three million
women and one million men have one or more severe
headaches every month. Migraines often begin in adolescence, and are rare after age 60.
Two types of migraine are recognized. Eighty percent of migraine sufferers experience ‘‘migraine without aura’’ (common migraine). In ‘‘migraine with
aura,’’ or classic migraine, the pain is preceded or
accompanied by visual or other sensory disturbances,
including hallucinations, partial obstruction of the
visual field, numbness or tingling, or a feeling of heaviness. Symptoms are often most prominent on one
side of the head or body, and may begin as early as
72 hours before the onset of pain.

Causes and symptoms
Causes
The physiological basis of migraine has proved difficult to uncover. Genetics appear to play a part for many,
but not all, people with migraine. There are a multitude of
potential triggers for a migraine attack, and recognizing
one’s own set of triggers is the key to prevention.
PHYSIOLOGY. The most widely accepted hypoth-

esis of migraine suggests that a migraine attack is
precipitated when pain-sensing nerve cells in the
brain (called nociceptors) release chemicals called neuropeptides. At least one of the neurotransmitters,
2436

substance P, increases the pain sensitivity of other
nearby nociceptors.
Other neuropeptides act on the smooth muscle
surrounding cranial blood vessels. This smooth muscle regulates blood flow in the brain by relaxing or
contracting, thus constricting the enclosed blood vessels and stimulating adjacent pain receptors. At the
onset of a migraine headache, neuropeptides are
thought to cause muscle relaxation, allowing vessel
dilation and increased blood flow. Other neuropeptides increase the leakiness of cranial vessels, allowing fluid leak, and promote inflammation and tissue
swelling. The pain of migraine is though to result
from this combination of increased pain sensitivity,
tissue and vessel swelling, and inflammation. The
aura seen during a migraine may be related to constriction in the blood vessels that dilate in the headache phase.
GENETICS. Susceptibility to some types of
migraine is inherited. A child of a migraine sufferer
has as much as a 50% chance of developing
migraines. If both parents are affected, the chance
rises to 70%. In 2002, a team of Australian researchers identified a region on human chromosome 1 that
influences susceptibility to migraine. It is likely that
more than one gene is involved in the inherited forms
of the disorder. Many cases of migraine, however,
have no obvious familial basis. It is likely that the
genes that are involved set the stage for migraine, and
that full development requires environmental influences, as well.

Two groups of Italian researchers have recently
identified two loci on human chromosomes 1 and 14
respectively that are linked to migraine headaches.
The locus on chromosome 1q23 has been linked to
familial hemiplegic migraine type 2, while the locus
on chromosome 14q21 is associated with migraine
without aura.
TRIGGERS. A wide variety of foods, drugs, environmental cues, and personal events are known to
trigger migraines. It is not known how most triggers
set off the events of migraine, nor why individual
migraine sufferers are affected by particular triggers
but not others.

Common food triggers include:


cheese



alcohol



caffeine products, and caffeine withdrawal



chocolate



intensely sweet foods
GALE ENCYCLOPEDIA OF MEDICINE

dairy products



fermented or pickled foods



citrus fruits



nuts



processed foods, especially those containing nitrites,
sulfites, or monosodium glutamate (msg)

sensitivity to light and sound, and intolerance of
food or odors. Blurred vision is common.
Migraine pain tends to intensify over the first 30
minutes to several hours, and may last from several
hours to a day or longer. Afterward, the affected
person is usually weary, and sensitive to sudden head
movements.

Environmental and event-related triggers include:


stress or time pressure



menstrual periods, menopause



sleep changes or disturbances, oversleeping



prolonged overexertion or uncomfortable posture



hunger or fasting



odors, smoke, or perfume



strong glare or flashing lights
Drugs which may trigger migraine include:



oral contraceptives



estrogen replacement therapy



nitrates



theophylline



reserpine



nifedipine



indomethicin



cimetidine



decongestant overuse



analgesic overuse



benzodiazepine withdrawal
Symptoms

Migraine without aura may be preceded by elevations in mood or energy level for up to 24 hours before
the attack. Other pre-migraine symptoms may include
fatigue, depression, and excessive yawning.
Aura most often begins with shimmering, jagged
arcs of white or colored light progressing over the
visual field in the course of 10-20 minutes. This may
be preceded or replaced by dark areas or other visual
disturbances. Numbness and tingling is common, especially of the face and hands. These sensations may
spread, and may be accompanied by a sensation of
weakness or heaviness in the affected limb.
The pain of migraine is often present only on one
side of the head, although it may involve both, or
switch sides during attacks. The pain is usually throbbing, and may range from mild to incapacitating. It is
often accompanied by nausea or vomiting, painful
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Ideally, migraine is diagnosed by a careful medical
history. Unfortunately, migraine is underdiagnosed
because many doctors tend to minimize its symptoms
as ‘‘just a headache.’’ According to a 2003 study, 64%
of migraine patients in the United Kingdom and 77%
of those in the United States never receive a correct
medical diagnosis for their headaches.
So far, laboratory tests and such imaging studies
as computed tomography (CT scan) or magnetic resonance imaging (MRI) scans have not been useful for
identifying migraine. However, these tests may be
necessary to rule out a brain tumor or other structural
causes of migraine headache in some patients.

Treatment
Once a migraine begins, the person will usually
seek out a dark, quiet room to lessen painful stimuli.
Several drugs may be used to reduce the pain and
severity of the attack.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
are helpful for early and mild headache. NSAIDs
include acetaminophen, ibuprofen, naproxen, and
others. A recent study concluded that a combination
of acetaminophen, aspirin, and caffeine could effectively relieve symptoms for many migraine patients.
One such over-the-counter preparation is available as
Exedrin Migraine.
More severe or unresponsive attacks may be treated
with drugs that act on serotonin receptors in the smooth
muscle surrounding cranial blood vessels. Serotonin,
also known as 5-hydroxytryptamine, constricts these
vessels, relieving migraine pain. Drugs that mimic serotonin and bind to these receptors have the same effect.
The oldest of them is ergotamine, a derivative of a
common grain fungus. Ergotamine and dihydroergotamine are used for both acute and preventive treatment.
Derivatives with fewer side effects have come onto the
market in the past decade, including sumatriptan
(Imitrex). Some of these drugs are available as nasal
sprays, intramuscular injections, or rectal suppositories
for patients in whom vomiting precludes oral
2437

Migraine headache



Migraine headache

administration. Other drugs used for acute attacks
include meperidine and metoclopramide.

KEY TERMS

Studies are showing that rizatriptan is a promising
drug for the treatment of migraines. One study showed
that 10mg of rizatriptan provided relief to 90% of the
patients in the study group and kept 50% of them
pain-free 2 hours after taking the medication.
Sumatriptan has been on the market since 1993,
while rizatriptan became available in 1998.

Aura—A group of visual or other sensations that
precedes the onset of a migraine attack.
Coenzyme Q10—A substance used by cells in the
human body to produce energy for cell maintenance and growth. It is being studied as a possible
preventive for migraine headaches.

Sumatriptan and other triptan drugs (zolmitriptan, rizatriptan, naratriptan, almotriptan, and frovatriptan) should not be taken by people with any kind
of vascular disease because they cause coronary artery
narrowing. Otherwise these drugs have been shown to
be very safe.
Continued use of some antimigraine drugs can
lead to ‘‘rebound headache,’’ marked by frequent or
chronic headaches, especially in the early morning
hours. Rebound headache can be avoided by using
antimigraine drugs under a doctor’s supervision,
with the minimum dose necessary to treat symptoms.
Tizanidine (Zanaflex) has been reported to be effective
in treating rebound headaches when taken together
with an NSAID.

Alternative treatments
Alternative treatments are aimed at prevention
of migraine. Migraine headaches are often linked
with food allergies or intolerances. Identification
and elimination of the offending food or foods can
decrease the frequency of migraines and/or alleviate
these headaches altogether. Herbal therapy with
feverfew (Chrysanthemum parthenium) may lessen
the frequency of attacks. Learning to increase the
flow of blood to the extremities through biofeedback
training may allow a patient to prevent some of the
vascular changes once a migraine begins. During a
migraine, keep the lights low; put the feet in a tub of
hot water and place a cold cloth on the occipital
region (the back of the head). This treatment draws
the blood to the feet and decreases the pressure in
the head.

Prognosis
Most people with migraines can bring their attacks
under control through recognizing and avoiding triggers, and by use of appropriate drugs when migraine
occurs. Some people with severe migraines do not
respond to preventive or drug therapy. Migraines
usually wane in intensity by age 60 and beyond.
2438

Nociceptor—A specialized type of nerve cell that
senses pain.

Prevention
The frequency of migraine may be lessened by
avoiding triggers. It is useful to keep a headache journal, recording the particulars and noting possible triggers for each attack. Specific measures which may help
include:


Eating at regular times, and not skipping meals.



Reducing the use of caffeine and pain-relievers.



Restricting physical exertion, especially on hot days.



Keeping regular sleep hours, but not oversleeping.



Managing one’s time efficiently in order to avoid
stress at work and home.

Some drugs can be used for migraine prevention,
including specific members of these drug classes:


beta blockers



tricyclic antidepressants



calcium channel blockers



selective serotinin reuptake inhibitors (SSRIs)



monoamine oxidase inhibitors (MAOIs)



serotonin antagonists

One substance that is being studied as a possible
migraine preventive is coenzyme Q10, a compound
used by cells to produce energy needed for cell growth
and maintenance. Coenzyme Q10 has been studied as a
possible complementary treatment for cancer. Its use
in preventing migraines is encouraging and merits
further study.
A study published in early 2003 reported that
three drugs currently used to treat disorders of muscle
tone are being explored as possible preventive treatments for migraine. They are botulinum toxin type A
(Botox), baclofen (Lioresal), and tizanidine
(Zanaflex). Early results of open trials of these medications are positive.
GALE ENCYCLOPEDIA OF MEDICINE

A natural preparation made from butterbur root
(Petasites hybridus) has been sold in Germany since
the 1970s as a migraine preventive under the trade
name Petadolex. Petadolex has been available in the
United States since December 1998 and has passed
several clinical safety and postmarketing surveillance
trials.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Migraine. ’’ Section 14, Chapter 168. In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Headaches.’’ New York: Simon & Schuster, 2002.
Rakel, Robert. Conn’s Current Therapy: Latest Approved
Methods of Treatment for the Practicing Physician.
Philadelphia: W.B. Saunders Company, 2001.
Tierney, Lawrence, et al. Current Medical Diagnosis and
Treatment. Los Altos, CA: Lange Medical Publications,
2001.
PERIODICALS

Bendtsen, L. ‘‘Sensitization: Its Role in Primary Headache.’’
Current Opinion in Investigational Drugs 3 (March
2002): 449–453.
Corbo, J. ‘‘The Role of Anticonvulsants in Preventive
Migraine Therapy.’’ Current Pain and Headache
Reports 7 (February 2003): 63–66.
Danesch, U., and R. Rittinghausen. ‘‘Safety of a Patented
Special Butterbur Root Extract for Migraine
Prevention.’’ Headache 43 (January 2003): 76–78.
Diamond, S., and R. Wenzel. ‘‘Practical Approaches to
Migraine Management.’’ CNS Drugs 16 (2002):
385–403.
Freitag, F. G. ‘‘Preventative Treatment for Migraine and
Tension-Type Headaches: Do Drugs Having Effects on
Muscle Spasm and Tone Have a Role?’’ CNS Drugs 17
(2003): 373–381.
Lea, R. A., A. G. Shepherd, R. P. Curtain, et al. ‘‘A Typical
Migraine Susceptibility Region Localizes to
Chromosome 1q31.’’ Neurogenetics 4 (March 2002):
17–22.
Lipton, R. B., A. I. Scher, T. J. Steiner, et al. ‘‘Patterns of
Health Care Utilization for Migraine in England and in
the United States.’’ Neurology 60 (February 11, 2003):
441–448.
GALE ENCYCLOPEDIA OF MEDICINE

Marconi, R., M. De Fusco, P. Aridon, et al. ‘‘Familial
Hemiplegic Migraine Type 2 is Linked to 0.9Mb Region
on Chromosome 1q23.’’ Annals of Neurology 53 (March
2003): 376–381.
Rozen, T. D., M. L. Oshinsky, C. A. Gebeline, et al. ‘‘Open
Label Trial of Coenzyme Q10 as a Migraine
Preventive.’’ Cephalalgia 22 (March 2002): 137–141.
Sheftell, F. D., and S. J. Tepper. ‘‘New Paradigms in the
Recognition and Acute Treatment of Migraine.’’
Headache 42 (January 2002): 58–69.
Sinclair, Steven. ‘‘Migraine Headaches: Nutritional,
Botanical and Other Alternative Approaches.’’
Alternative Medicine Review 4 (1999): 86–95.
Soragna, D., A. Vettori, G. Carraro, et al. ‘‘A Locus for
Migraine Without Aura Maps on Chromosome
14q21.2-q22.3.’’ American Journal of Human Genetics
72 (January 2003): 161–167.
Tepper, S. J., and D. Millson. ‘‘Safety Profile of the
Triptans.’’ Expert Opinion on Drug Safety 2 (March
2003): 123–132.
ORGANIZATIONS

American Council for Headache Education. 19 Mantua
Road, Mt. Royal, NJ 08061. (609) 423-0043 or (800)
255-2243. <http://www.achenet.org>.
National Headache Foundation. 428 West St. James Place,
Chicago, IL 60614. (773) 388-6399 or (800) 843-2256.
<http://www.headaches.org>.
U. S. Food and Drug Administration (FDA). 5600 Fishers
Lane, Rockville, MD 20857. (888) 463-6332. <http://
www.fda.gov>.
OTHER

American Medical Association. ‘‘Migraine.’’ <http://
www.ama-assn.org/special/migraine/>.

Kim A. Sharp, M.Ln.
Rebecca J. Frey, PhD

Miliaria see Prickly heat

Mineral deficiency
Definition
The term mineral deficiency means a condition
where the concentration of any one of the minerals
essential to human health is abnormally low in the
body. In some cases, an abnormally low mineral concentration is defined as that which leads to an impairment in a function dependent on the mineral. In other
cases, the convention may be to define an abnormally
low mineral concentration as a level lower than that
found in a specific healthy population.
2439

Mineral deficiency

Anti-epileptic drugs, which are also known as
anticonvulsants, are also being studied as possible
migraine preventives. As of 2003, sodium valproate
(Epilim) is the only drug approved by the Food and
Drug Administration (FDA) for prevention of
migraine. Such newer anticonvulsants as gabapentin
(Neurontin) and topiramate (Topamax) are presently
being evaluated as migraine preventives.

Mineral deficiency

The mineral nutrients are defined as all the inorganic elements or inorganic molecules that are
required for life. As far as human nutrition is concerned, the inorganic nutrients include water, sodium,
potassium, chloride, calcium, phosphate, sulfate, magnesium, iron, copper, zinc, manganese, iodine, selenium, and molybdenum. Some of the inorganic
nutrients, such as water, do not occur as single
atoms, but occur as molecules. Other inorganic nutrients that are molecules include phosphate, sulfate, and
selenite. Phosphate contains an atom of phosphorus.
Sulfate contains an atom of sulfur. We do not need to
eat sulfate, since the body can acquire all the sulfate it
needs from protein. Selenium occurs in foods as selenite and selenate.
There is some evidence that other inorganic nutrients, such as chromium and boron, play a part in
human health, but their role is not well established.
Fluoride has been proven to increase the strength of
bones and teeth, but there is little or no reason to
believe that is needed for human life.
The mineral content of the body may be measured
by testing samples of blood plasma, red blood cells, or
urine. In the case of calcium and phosphate deficiency,
the diagnosis may also involve taking x rays of the
skeleton. In the case of iodine deficiency, the diagnosis
may include examining the patient’s neck with the eyes
and hands. In the case of iron deficiency, the diagnosis
may include the performance of a stair-stepping test by
the patient. Since all the minerals serve strikingly different functions in the body, the tests for the corresponding deficiency are markedly different from each other.

Description
Laboratory studies with animals have revealed
that severe deficiencies in any one of the inorganic
nutrients can result in very specific symptoms, and
finally in death, due to the failure of functions associated with that nutrient. In humans, deficiency in one
nutrient may occur less often than deficiency in several
nutrients. A patient suffering from malnutrition is deficient in a variety of nutrients. In the United States,
malnutrition is most often found among severe alcoholics. In part, this is because the alcohol consumption
may supply half of the energy requirement, resulting in
a mineral and vitamin intake of half the expected level.
Deficiencies in one nutrient do occur, for example, in
human populations living in iodine-poor regions of
the world, and in iron deficient persons who lose
excess iron by abnormal bleeding.
Inorganic nutrients have a great variety of functions in the body. Water, sodium, and potassium
2440

deficiencies are most closely associated with abnormal
nerve action and cardiac arrhythmias. Deficiencies in
these nutrients tend to result not from a lack of content
in the diet, but from excessive losses due to severe
diarrhea and other causes. Iodine deficiency is a global
public health problem. It occurs in parts of the world
with iodine-deficient soils, and results in goiter, which
involves a relatively harmless swelling of the neck, and
cretinism, a severe birth defect. The only use of iodine
in the body is for making thyroid hormone. However,
since thyroid hormone has a variety of roles in development of the embryo, iodine deficiency during pregnancy results in a number of birth defects.
Calcium deficiency due to lack of dietary calcium
occurs only rarely. However, calcium deficiency due to
vitamin D deficiency can be found among certain
populations. Vitamin D is required for the efficient
absorption of calcium from the diet, and hence vitamin D deficiency in growing infants and children can
result in calcium deficiency.
Dietary phosphate deficiency is rare because
phosphate is plentiful in plant and animal foods, but
also because phosphate is efficiently absorbed from
the diet into the body. Iron deficiency causes anemia
(lack of red blood cells), which results in tiredness and
shortness of breath.
Dietary deficiencies in the remaining inorganic
nutrients tend to be rare. Magnesium deficiency is
uncommon, but when it occurs it tends to occur in
chronic alcoholics, in persons taking diuretic drugs,
and in those suffering from severe and prolonged diarrhea. Magnesium deficiency tends to occur with the
same conditions that provoke deficiencies in sodium
and potassium. Zinc deficiency is rare, but it has been
found in impoverished populations in the Middle
East, who rely on unleavened whole wheat bread as a
major food source. Copper deficiency is also rare, but
dramatic and health-threatening changes in copper
metabolism occur in two genetic diseases, Wilson’s
disease and Menkes’ disease.
Selenium deficiency may occur in regions of the
world where the soils are poor in selenium. Low-selenium soils can produce foods that are also low in
selenium. Premature infants may also be at risk for
selenium deficiency. Manganese deficiency is very
rare. Experimental studies with humans fed a manganese deficient diet have revealed that the deficiency
produces a scaly, red rash on the skin of the upper
torso. Molybdenum deficiency has probably never
occurred, but indirect evidence suggests that if molybdenum deficiency could occur, it would result in mental retardation and death.
GALE ENCYCLOPEDIA OF MEDICINE

Sodium deficiency (hyponatremia) and water deficiency are the most serious and widespread deficiencies in the world. These deficiencies tend to arise from
excessive losses from the body, as during prolonged
and severe diarrhea or vomiting. Diarrheal diseases are
a major world health problem, and are responsible for
about a quarter of the 10 million infant deaths that
occur each year. Nearly all of these deaths occur in
impoverished parts of Africa and Asia, where they
result from contamination of the water supply by
animal and human feces.
The main concern in treating diarrheal diseases is
dehydration, that is, the losses of sodium and water
which deplete the fluids of the circulatory system (the
heart, veins, arteries, and capillaries). Severe losses of
the fluids of the circulatory system result in shock.
Shock nearly always occurs when dehydration is
severe enough to produce a 10% reduction in body
weight. Shock, which is defined as inadequate supply
of blood to the various tissues of the body, results in a
lack of oxygen to all the cells of the body. Although
diarrheal fluids contain a number of electrolytes, the
main concern in avoiding shock is the replacement of
sodium and water.
Sodium deficiency and potassium deficiency also
frequently result during treatment with drugs called
diuretics. Diuretics work because they cause loss of
sodium from the body. These drugs are used to treat
high blood pressure (hypertension), where the resulting
decline in blood pressure reduces the risk for cardiovascular disease. However, diuretics can lead to
sodium deficiency, resulting in low plasma sodium
levels. A side effect of some diuretics is excessive loss
of potassium, and low plasma potassium (hypokalemia) may result.
Iodine deficiency tends to occur in regions of the
world where the soil is poor in iodine. Where soil used
in agriculture is poor in iodine, the foods grown in the
soil will also be low in iodine. An iodine intake of 0.100.15 mg/day is considered to be nutritionally adequate, while iodine deficiency occurs at below 0.05
mg/day. Goiter, an enlargement of the thyroid gland
(located in the neck), results from iodine deficiency.
Goiter continues to be a problem in eastern Europe,
parts of India and South America, and in Southeast
Asia. Goiter has been eradicated in the United States
because of the fortification of foods with iodine.
Iodine deficiency during pregnancy results in cretinism in the newborn. Cretinism involves mental retardation, a large tongue, and sometimes deafness,
muteness, and lameness.
GALE ENCYCLOPEDIA OF MEDICINE

Iron deficiency occurs due to periods of dietary
deficiency, rapid growth, and excessive loss of the
body’s iron. Human milk and cow milk both contains
low levels of iron. Infants are at risk for acquiring iron
deficiency because their rapid rate of growth needs a
corresponding increased supply of dietary iron, for use
in making blood and muscles. Human milk is a better
source of iron than cow milk, since about half of the
iron in human breast milk is absorbed by the infant’s
digestive tract. In contrast, only 10% of the iron in
cow milk is absorbed by the infant. Surveys of lowerincome families in the United States have revealed that
about 6% of the infants are anemic indicating a deficiency of iron in their diets. Blood loss that occurs with
menstruation in women, as well as with a variety of
causes of intestinal bleeding is a major cause of iron
deficiency. The symptoms of iron deficiency are generally limited to anemia, and the resulting tiredness,
weakness, and a reduced ability to perform physical
work.
Calcium and phosphate are closely related nutrients. About 99% of the calcium and 85% of the phosphate in the body occur in the skeleton, where they
exist as crystals of solid calcium phosphate. Both of
these nutrients occur in a great variety of foods. Milk,
eggs, and green, leafy vegetables are rich in calcium
and phosphate. Whole cow milk, for example, contains about 1.2 g calcium and 0.95 g phosphorus per kg
of food. Broccoli contains 1.0 g calcium and 0.67 g
phosphorus per kg food. Eggs supply about one third
of the calcium and phosphate of the overall population of the United States. Dietary deficiencies in calcium (hypocalcemia) or phosphate are extremely rare
throughout the world. Vitamin D deficiency can be
found among young infants, the elderly, and others
who may be shielded from sunshine for prolonged
periods of time. Vitamin D deficiency impairs the
absorption of calcium from the diet, and in this way
can provoke calcium deficiency even when the diet
contains adequate calcium.
Zinc deficiency has been found among peasant
populations in rural areas of the Middle East.
Unleavened whole wheat bread can account for 75%
of the energy intake in these areas. This diet, which
does not contain meat, does contain zinc, but it also
contains phytic acid at a level of about 3 g/day. The
phytic acid, which naturally occurs in wheat, inhibits
zinc absorption. The yeast used to leaven bread produces enzymes that inactivate the phytic acid.
Unleavened bread does not contain yeast, and therefore, contains intact phytic acid. The symptoms of zinc
deficiency include lack of sexual maturation, lack of
pubic hair, and small stature. The amount of phytic
2441

Mineral deficiency

Causes and symptoms

Mineral deficiency

acid in a typical American diet cannot provoke zinc
deficiency.
Zinc deficiency is relatively uncommon in the
United States, but it may occur in adults with alcoholism or intestinal malabsorption problems. Low plasma
zinc has been found in patients with alcoholic cirrhosis,
Crohn’s disease, and celiac disease. Experimental studies with humans have shown that the signs of zinc
deficiency are detectable after two to five weeks of
consumption of the zinc-free diet. The signs include a
rash and diarrhea. The rash occurs on the face, groin,
hands, and feet. These symptoms can easily be reversed
by administering zinc. An emerging concern is that
increased calcium intake can interfere with zinc absorption or retention. Hence, there is some interest in the
question of whether persons taking calcium to prevent
osteoporosis should also take zinc supplements.
Severe alterations in copper metabolism occur in
two genetic diseases, Wilson’s disease and Menkes’
disease. Both of these diseases are rare and occur in
about one in 100,000 births. Both diseases involve
mutations in copper transport proteins, that is, in
special channels that allow the passage of copper
ions through cell membranes. Menkes’ disease is a
genetic disease involving mental retardation and
death before the age of three years. The disease also
results in steely or kinky hair. The hair is tangled,
grayish, and easily broken. Menkes’ disease involves
a decrease in copper levels in the serum, liver, and
brain, and increases in copper in the cells of the intestines and kidney.
Selenium deficiency may occur in premature
infants, since this population naturally tends to have
low levels of plasma selenium. Full term infants have
plasma selenium levels of about 0.001-0.002 mM,
while premature infants may have levels about one
third this amount. Whether these lower levels result
in adverse consequences is not clear. Selenium deficiency occurs in regions of the world containing lowselenium soils. These regions include Keshan Province
in China, New Zealand, and Finland. In Keshan
Province, a disease (Keshan disease) occurs which
results in deterioration of regions of the heart and
the development of fibers in these regions. Keshan
disease, which may be fatal, is thought to result from
a combination of selenium deficiency and a virus.

Diagnosis
The diagnosis of deficiencies in water, sodium,
potassium, iron, calcium, and phosphate involve chemical testing of the blood plasma, urine, and red blood
cells.
2442

Iodine deficiency can be diagnosed by measuring
the concentration of iodine in the urine. A urinary
level greater than 0.05 mg iodine per gram creatinine
means adequate iodine status. Levels under 0.025 mg
iodine/g creatinine indicate a serious risk.
Normal blood serum magnesium levels are 1.2-2.0
mM. Magnesium deficiency results in hypomagnesemia, which is defined as serum magnesium levels
below 0.8 mM. Magnesium levels below 0.5 mM provoke a decline in serum calcium levels.
Hypomagnesemia can also result in low serum potassium. Some of the symptoms of hypomagnesemia,
which include twitching and convulsions, actually
result from the hypocalcemia. Other symptoms of
hypomagnesemia, such as cardiac arrhythmias, result
from the low potassium levels.
There is no reliable test for zinc deficiency. When
humans eat diets containing normal levels of zinc (16
mg/day), the level of urinary zinc is about 0.45 mg/
day, while humans consuming low-zinc diets (0.3 mg/
day) may have urinary levels of about 0.150 mg/day.
Plasma zinc levels tend to be maintained during a
dietary deficiency in zinc. Plasma and urinary zinc
levels can be influenced by a variety of factors, and
for this reason cannot provide a clear picture of zinc
status.
Selenium deficiency may be diagnosed by measuring the selenium in plasma (70 ng/mL) or red blood
cells (90 ng/mL), where the normal values are indicated. There is also some interest in measuring the
activity of an enzyme in blood platelets, in order to
assess selenium status. This enzyme is glutathione peroxidase. Platelets are small cells of the bloodstream
which are used mainly to allow the clotting of blood
after an injury.

Treatment
The treatment of deficiencies in sodium, potassium, calcium, phosphate, and iron usually involves
intravenous injections of the deficient mineral.
Iodine deficiency can be easily prevented and treated by fortifying foods with iodine. Table salt is fortified
with 100 mg potassium iodide per kg sodium chloride.
Goiter was once common in the United States in areas
from Washington State to the Great Lakes region, but
this problem has been eliminated by iodized salt. Public
health programs in impoverished countries have
involved injections of synthetic oils containing iodine.
Goiter is reversible but, cretinism is not.
Magnesium deficiency can be treated with a magnesium rich diet. If magnesium deficiency is due to a
GALE ENCYCLOPEDIA OF MEDICINE

Recommended
Dietary
Allowance—The
Recommended Dietary Allowances (RDAs) are
quantities of nutrients that are required each day
to maintain human health. RDAs are established by
the Food and Nutrition Board of the National
Academy of Sciences and may be revised every
few years. A separate RDA value exists for each
nutrient.

prolonged period of depletion, treatment may include
injections of magnesium sulfate (2.0 mL of 50%
MgSO4). Where magnesium deficiency is severe
enough to provoke convulsions, magnesium needs to
be administered by injections or infusions. For infusion, 500 mL of a 1% solution (1 gram/100 mL) of
magnesium sulfate is gradually introduced into a vein
over the course of about five hours.
Zinc deficiency and copper deficiency are quite
rare, but when they are detected or suspected, they
can be treated by consuming zinc or copper, on a
daily basis, at levels defined by the RDA.
Selenium deficiency in adults can be treated by
eating 100 mg selenium per day for a week, where the
selenium is supplied as selenomethionine. The incidence of Keshan disease in China has been reduced
by supplementing children with 1.0 mg sodium selenite
per week.

Dietary Allowances (RDA). Where a balanced diet is
not available, government programs for treating individuals, or for fortifying the food supply, may be used.
Government sponsored programs for the prevention
of iron deficiency and iodine deficiency are widespread
throughout the world. Selenium treatment programs
have been used in parts of the world where selenium
deficiency exists. Attention to potassium status, and to
the prevention of potassium deficiency, is an issue
mainly in patients taking diuretic drugs. In many
cases of mineral deficiency, the deficiency occurs
because of disease, and individual medical attention,
rather than preventative measures, is used. The prevention of calcium deficiency is generally not an issue
or concern, however calcium supplements are widely
used with the hope of preventing osteoporosis. The
prevention of deficiencies in magnesium, zinc, copper,
manganese, or molybdenum are not major health
issues in the United States. Ensuring an adequate
intake of these minerals, by eating a balanced diet or
by taking mineral supplements, is the best way to
prevent deficiencies.
Resources
BOOKS

Brody, Tom. Nutritional Biochemistry. San Diego:
Academic Press, 1998.

Tom Brody, PhD

Mineral excess see Mineral toxicity

Prognosis
In iodine deficiency, the prognosis for treating
goiter is excellent, however cretinism cannot be
reversed. The effects of iron deficiency are not lifethreatening and can be easily treated. The prognosis
for treating magnesium deficiency is excellent. The
symptoms may be relieved promptly or, at most,
within two days of starting treatment. In cases of
zinc deficiency in Iran and other parts of the Middle
East, supplementation of affected young adults with
zinc has been found to provoke the growth of pubic
hair and enlargement of genitalia to a normal size
within a few months.

Prevention
In the healthy population, all mineral deficiencies
can be prevented by the consumption of inorganic
nutrients at levels defined by the Recommended
GALE ENCYCLOPEDIA OF MEDICINE

Mineral toxicity
Definition
The term mineral toxicity means a condition
where the concentration in the body of any one of
the minerals is abnormally high, and where there is
an adverse effect on health.

Description
In general, mineral toxicity results when there is
an accidental consumption of too much of any
mineral, as with drinking ocean water (sodium toxicity) or with overexposure to industrial pollutants,
household chemicals, or certain drugs. Mineral toxicity may also apply to toxicity that can be the result of
certain diseases or injuries. For example, hemochromatosis leads to iron toxicity; Wilson’s disease results
2443

Mineral toxicity

KEY TERMS

Mineral toxicity

in copper toxicity; severe trauma can lead to hyperkalemia (potassium toxicity).
The mineral nutrients are defined as all the inorganic elements or inorganic molecules that are
required for life. As far as human nutrition is concerned, the inorganic nutrients include water, sodium,
potassium, chloride, calcium, phosphate, sulfate, magnesium, iron, copper, zinc, manganese, iodine, selenium, and molybdenum.
The mineral content of the body may be measured
by testing samples of blood plasma, red blood cells,
and urine.

Causes and symptoms
An increase in the concentrations of sodium in the
bloodstream can be toxic. The normal concentration
of sodium in the blood plasma is 136-145 mM, while
levels over 152 mM can result in seizures and death.
Increased plasma sodium, which is called hypernatremia, causes various cells of the body, including those
of the brain, to shrink. Shrinkage of the brain cells
results in confusion, coma, paralysis of the lung muscles, and death. Death has occurred where table salt
(sodium chloride) was accidently used, instead of
sugar, for feeding infants. Death due to sodium toxicity has also resulted when baking soda (sodium bicarbonate) was used during attempted therapy of
excessive diarrhea or vomiting. Although a variety of
processed foods contain high levels of sodium chloride, the levels used are not enough to result in sodium
toxicity.
The normal level of potassium in the bloodstream
is in the range of 3.5-5.0 mM, while levels of 6.3-8.0
mM (severe hyperkalemia) result in cardiac arrhythmias or even death due to cardiac arrest. Potassium is
potentially quite toxic, however toxicity or death due
to potassium poisoning is usually prevented because of
the vomiting reflex. The consumption of food results
in mild increases in the concentration of potassium in
the bloodstream, but levels of potassium do not
become toxic because of the uptake of potassium by
various cells of the body, as well as by the action of the
kidneys transferring the potassium ions from the
blood to the urine. The body’s regulatory mechanisms
can easily be overwhelmed, however, when potassium
chloride is injected intravenously, as high doses of
injected potassium can easily result in death.
Iodine toxicity can result from an intake of 2.0 mg
of iodide per day. The toxicity results in impairment of
the creation of thyroid hormone, resulting in lower
levels of thyroid hormone in the bloodstream. The
2444

thyroid gland enlarges, as a consequence, and goiter
is produced. This enlargement is also called hyperthyroidism. Goiter is usually caused by iodine deficiency.
In addition to goiter, iodine toxicity produces ulcers
on the skin. This condition has been called ‘‘kelp
acne,’’ because of its association with eating kelp, an
ocean plant, which contains high levels of iodine.
Iodine toxicity occurs in Japan, where large amounts
of seaweed are consumed.
Iron toxicity is not uncommon, due to the wide
distribution of iron pills. A lethal dose of iron is in the
range of 200-250 mg iron/kg body weight. Hence, a
child who accidently eats 20 or more iron tablets may
die as a result of iron toxicity. Within six hours of
ingestion, iron toxicity can result in vomiting, diarrhea,
abdominal pain, seizures, and possibly coma. A latent
period, where the symptoms appear to improve, may
occur but it is followed by shock, low blood glucose,
liver damage, convulsions, and death, occuring 12-48
hours after toxic levels of iron are ingested.
Nitrite poisoning should be considered along with
iron toxicity, since nitrite produces its toxic effect by
reacting with the iron atom of hemoglobin.
Hemoglobin is an iron-containing protein that resides
within the red blood cells. This protein is responsible
for the transport of nearly all of the oxygen, acquired
from the lungs, to various tissues and organs of the
body. Hemoglobin accounts for the red color of our
red blood cells. A very small fraction of our hemoglobin spontaneously oxidizes per day, producing a protein of a slightly different structure, called
methemoglobin. Normally, the amount of methemoglobin constitutes less than 1% of the total hemoglobin. Methemoglobin can accumulate in the blood as a
result of nitrite poisoning. Infants are especially susceptible to poisoning by nitrite.
Nitrate, which is naturally present in green leafy
vegetables and in the water supply is rapidly converted
to nitrite by the naturally occurring bacteria residing
on our tongue, as well as in the intestines, and then
absorbed into the bloodstream. The amount of nitrate
that is supplied by leafy vegetables and in drinking
water is generally about 100-170 mg/day. The amount
of nitrite supplied by a typical diet is much less, that is,
than 0.1 mg nitrite/day. Poisoning by nitrite, or nitrate
after its conversion to nitrite, results in the inability of
hemoglobin to carry oxygen throughout the body.
This condition can be seen by the blue color of the
skin. Adverse symptoms occur when over 30% of the
hemoglobin has been converted to methemoglobin,
and these symptoms include cardiac arrhythmias,
headache, nausea and vomiting, and in severe cases,
seizures.
GALE ENCYCLOPEDIA OF MEDICINE

Zinc toxicity is rare, but it can occur in metal
workers who are exposed to fumes containing zinc.
Excessive dietary supplements of zinc can result in
nausea, vomiting, and diarrhea. The chronic intake
of excessive zinc supplements can result in copper
deficiency, as zinc inhibits the absorption of copper.
Severe alterations in copper metabolism occur in
two genetic diseases, Wilson’s disease and Menkes’
disease. Both of these diseases are rare and occur in
about one in 100,000 births. Both diseases involve
mutations in the proteins that transport copper, that
is, in special channels that allow the passage of copper
ions through cell membranes. Wilson’s disease tends
to occur in teenagers and in young adults, and then
remain for the lifetime. Copper accumulates in the
liver, kidney, and brain, resulting in damage to the
liver and nervous system. Wilson’s disease can be successfully controlled by lifelong treatment with d-penicillamine. Treatment also involves avoiding foods that
are high in copper, such as liver, nuts, chocolate, and
mollusks. After an initial period of treatment with
penicillamine, Wilson’s disease may be treated with
zinc (150 mg oral Zn/day). The zinc inhibits the
absorption of dietary copper.
Selenium toxicity occurs in regions of the world,
including some parts of China, where soils contain
high levels of selenium. A daily intake of 0.75-5.0 mg
selenium may occur in these regions, due to the presence of selenium in foods and water. Early signs of
selenium toxicity include nausea, weakness, and diarrhea. With continued intake of selenium, changes in
fingernails and hair loss results, and damage to the
nervous system occurs. The breath may acquire a
garlic odor, as a result of the increased production of
dimethylselenide in the body, and its release via the
lungs.
Manganese toxicity occurs in miners in manganese mines, where men breath air containing dust
bearing manganese at a concentration of 5-250 mg/
cubic meter. Manganese toxicity in miners has been
documented in Chile, India, Japan, Mexico, and
GALE ENCYCLOPEDIA OF MEDICINE

elsewhere. Symptoms of manganese poisoning typically occur within several months or years of exposure.
These symptoms include a mental disorder resembling
schizophrenia, as well as hyperirritability, violent acts,
hallucinations, and difficulty in walking.

Diagnosis
The initial diagnosis of mineral toxicity involves
questioning the patient in order to determine any unusual aspects of the diet, unusual intake of drugs and
chemicals, and possible occupational exposure.
Diagnosis of mineral toxicities also involves measuring the metal concentration in the plasma or urine.
Concentrations that are above the normal range can
confirm the initial, suspected diagnosis.

Treatment
Iron toxicity is treated by efforts to remove
remaining iron from the stomach, by use of a solution
of 5% sodium bicarbonate. Where plasma iron levels
are above 0.35 mg/dL, the patient is treated with
deferoxamine. Treatment of manganese toxicity
involves removal of the patient from the high manganese environment, as well as lifelong doses of the drug
L-dopa. The treatment is only partially successful.
Treatment of nitrite or nitrate toxicity involves inhalation of 100% oxygen for several hours. If oxygen
treatment is not effective, then methylene blue may
be injected, as a 1.0% solution, in a dose of 1.0 mg
methylene blue/kg body weight.

Prognosis
The prognosis for treating toxicity due to sodium,
potassium, calcium, and phosphate is usually excellent. Toxicity due to the deposit of calcium phosphate
crystals is not usually reversible. The prognosis for
treating iodine toxicity is excellent. For any mineral
overdose that causes coma or seizures, the prognosis
for recovery is often poor, and death results in a small
fraction of patients. For any mineral toxicity that
causes nerve damage, the prognosis is often fair to
poor.

Prevention
When mineral toxicity results from the excessive
consumption of mineral supplements, toxicity can be
prevented by not using supplements. In the case of
manganese, toxicity can be prevented by avoiding
work in manganese mines. In the case of iodine, toxicity can be prevented by avoiding overconsumption of
2445

Mineral toxicity

Calcium and phosphate are closely related nutrients. Calcium toxicity is rare, but overconsumption of
calcium supplements may lead to deposits of calcium
phosphate in the soft tissues of the body. Phosphate
toxicity can occur with overuse of laxatives or enemas
that contain phosphate. Severe phosphate toxicity can
result in hypocalcemia, and in various symptoms
resulting from low plasma calcium levels. Moderate
phosphate toxicity, occurring over a period of months,
can result in the deposit of calcium phosphate crystals
in various tissues of the body.

Minerals

seaweed or kelp. In the case of selenium toxicity that
arises due to high-selenium soils, toxicity can be prevented by relying on food and water acquired from a
low-selenium region.
Resources
BOOKS

Brody, Tom. Nutritional Biochemistry. San Diego:
Academic Press, 1998.

Tom Brody, PhD

Minerals
Definition
The minerals (inorganic nutrients) that are relevant to human nutrition include water, sodium, potassium, chloride, calcium, phosphate, sulfate,
magnesium, iron, copper, zinc, manganese, iodine,
selenium, and molybdenum. Cobalt is a required
mineral for human health, but it is supplied by vitamin
B12. Cobalt appears to have no other function, aside
from being part of this vitamin. There is some evidence
that chromium, boron, and other inorganic elements
play some part in human nutrition, but the evidence is
indirect and not yet convincing. Fluoride seems not to
be required for human life, but its presence in the diet
contributes to long term dental health. Some of the
minerals do not occur as single atoms, but occur as
molecules. These include water, phosphate, sulfate,
and selenite (a form of selenium). Sulfate contains an
atom of sulfur. We do not need to eat sulfate, since the
body can acquire all the sulfate it needs from protein.
The statement that various minerals, or inorganic
nutrients, are required for life means that their continued supply in the diet is needed for growth, maintenance of body weight in adulthood, and for
reproduction. The amount of each mineral that is
needed to support growth during infancy and childhood, to maintain body weight and health, and to
facilitate pregnancy and lactation, are listed in a table
called the Recommended Dietary Allowances (RDA).
This table was compiled by the Food and Nutrition
Board, a committee that serves the United States government. All of the values listed in the RDA indicate
the daily amounts that are expected to maintain health
throughout most of the general population. The actual
levels of each inorganic nutrient required by any given
individual is likely to be less than that stated by the
2446

RDA. The RDAs are all based on studies that provided the exact, minimal requirement of each mineral
needed to maintain health. However, the RDA values
are actually greater than the minimal requirement, as
determined by studies on small groups of healthy
human subjects, in order to accomodate the variability
expected among the general population.
The RDAs for adult males are 800 mg of calcium,
800 mg of phosphorus, 350 mg of magnesium, 10 mg
of iron, 15 mg of zinc, 0.15 mg of iodine, and 0.07 mg
of selenium. The RDA for sodium is expressed as a
range (0.5-2.4 g/day). The minimal requirement for
chloride is about 0.75 g/day, and the minimal requirement for potassium is 1.6-2.0 g/day, though RDA
values have not been set for these nutrients. The
RDAs for several other minerals has not been determined, and here the estimated safe and adequate daily
dietary intake has been listed by the Food and
Nutrition Board. These values are listed for copper
(1.5-3.0 mg), manganese (2-5 mg), fluoride (1.5-4.0
mg), molybdenum (0.075-0.25 mg), and chromium
(0.05-0.2 mg). In noting the appearance of chromium
in this list, one should note that the function of chromium is essentially unknown, and evidence for its
necessity exists only for animals, and not for human
beings. In considering the amount of any mineral used
for treating mineral deficiency, one should compare
the recommended level with the RDA for that mineral.
Treatment at a level that is one tenth of the RDA
might not be expected to be adequate, while treatment
at levels ranging from 10-1,000 times the RDA might
be expected to exert a toxic effect, depending on the
mineral. In this way, one can judge whether any claim
of action, for a specific mineral treatment, is likely to
be adequate or appropriate.

Purpose
People are treated with minerals for several reasons. The primary reason is to relieve a mineral deficiency, when a deficiency has been detected. Chemical
tests suitable for the detection of all mineral deficiencies are available. The diagnosis of the deficiency is
often aided by tests that do not involve chemical reactions, such as the hematocrit test for the red blood cell
content in blood for iron deficiency, the visual examination of the neck for iodine deficiency, or the examination of bones by densitometry for calcium
deficiency. Mineral treatment is conducted after a
test and diagnosis for iron-deficiency anemia, in the
case of iron, and after a test and diagnosis for hypomagnesemia, in the case of magnesium, to give two
examples.
GALE ENCYCLOPEDIA OF MEDICINE

Most minerals are commercially available at
supermarkets, drug stores, and specialty stores.
There is reason to believe that the purchase and consumption of most of these minerals is beneficial to
health for some, but not all, of the minerals.
Potassium supplements are useful for reducing blood
pressure, in cases of persons with high blood pressure.
The effect of potassium varies from person to person.
The consumption of calcium supplements is likely to
have some effect on reducing the risk for osteoporosis.
The consumption of selenium supplements is expected
to be of value only for residents of Keshan Province,
China, because of the established association of selenium deficiency in this region with ‘‘Keshan disease.’’

Precautions
During emergency treatment of sodium deficiency
(hyponatremia), potassium deficiency (hypokalemia),
and calcium deficiency (hypocalcemia) with intravenous injections, extreme caution must be taken to
avoid producing toxic levels of each of these minerals
(hypernatremia, hyperkalemia, and hypercalcemia), as
mineral toxicity can be life-threatening in some
instances. The latter three conditions can be life threatening. Selenium is distinguished among most of the
nutrients in that dietary intakes at levels only ten times
that of the RDA can be toxic. Hence, one must guard
against any overdose of selenium. Calcium and zinc
supplements, when taken orally, are distinguished
among most of the other minerals in that their toxicity
is relatively uncommon.

Description
Minerals are used in treatments by three methods,
namely, by replacing a poor diet with a diet that
supplies the RDA, by consuming oral supplements,
or by injections or infusions. Injections are especially
useful for infants, for mentally disabled persons, or
where the physician wants to be totally sure of compliance. Infusions, as well as injections, are essential
for medical emergencies, as during mineral deficiency
GALE ENCYCLOPEDIA OF MEDICINE

situations like hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia. Oral mineral supplements are especially useful for mentally alert persons
who otherwise cannot or will not consume food that is
a good mineral source, such as meat. For example, a
vegetarian who will not consume meat may be encouraged to consume oral supplements of iron, as well as
supplements of vitamin B12.
Iron treatment is used for young infants, given as
supplements of 7 mg of iron per day to prevent anemia. Iron is also supplied to infants via the food
industry’s practice of including iron at 12 mg/L in
cow milk-based infant formulas, as well as adding
powdered iron at levels of 50 mg iron per 100 g dry
infant cereal.
Calcium supplements, along with estrogen and
calcitonin therapy, are commonly used in the prevention and treatment of osteoporosis. Estrogen and calcitonin are naturally occurring hormones. Bone loss
occurs with diets supplying under 400 mg Ca/day.
Bone loss can be minimized with the consumption of
the RDA for calcium. There is some thought that all
postmenopausal women should consume 1,000–1,500
mg of calcium per day. These levels are higher than the
RDA. There is some evidence that such supplementation can reduce bone losses in some bones, such as the
elbow (ulna), but not in other bones. Calcium absorption by the intestines decreases with aging, especially
after the age of 70. The regulatory mechanisms of the
intestines that allow absorption of adequate calcium
(500 mg Ca/day or less) may be impaired in the elderly.
Because of these changes, there is much interest in
increasing the RDA for calcium for older women.
Fluoride has been proven to reduce the rate of
tooth decay. When fluoride occurs in the diet, it is
incorporated into the structure of the teeth, and
other bones. The optimal range of fluoride in drinking
water is 0.7-1.2 mg/L. This level results in a reduction
in the rate of tooth decay by about 50%. The
American Dental Association recommends that persons living in areas lacking fluoridated water take
fluoride supplements. The recommendation is 0.25
mg F/day from the ages of 0-2 years, 0.5 mg F/day
for 2-3 years, and 1.0 mg F/day for ages 3-13 years.
Magnesium is often used to treat a dangerous
condition, called eclampsia, that occasionally occurs
during pregnancy. In this case, magnesium is used as a
drug, and not to relieve a deficiency. High blood pressure is a fairly common disorder during pregnancy,
affecting 1-5% of pregnant mothers. Hypertension
during pregnancy can result in increased release of
protein in the urine. In pregnancy, the combination
2447

Minerals

A second general reason for mineral treatment is
to prevent the development of a possible or expected
deficiency. Here, minerals are administered when tests
for possible mineral deficiency are not given.
Examples include the practice of giving young infants
iron supplements, and of the food industry’s practice
of supplementing infant formulas with iron. The purpose here is to reduce the risk for iron deficiency anemia. Another example is the practice of many women
of taking calcium supplements, with the hope of reducing the risk of osteoporosis.

Minnesota multiphasic personality inventory (MMPI-2)

of hypertension with increased urinary protein is
called preeclampsia. Preeclampsia is a concern during
pregnancies as it may lead to eclampsia. Eclampsia
involves convulsions and possibly death to the mother.
Magnesium sulfate is the drug of choice for preventing
the convulsions of eclampsia.
Treatment with cobalt, in the form of vitamin B12,
is used for relieving the symptoms of pernicious anemia. Pernicious anemia is a relatively common disease
which tends to occur in persons older than 40 years.
Free cobalt is never used for the treatment of any
disease.

into the bloodstream also allows the kidneys to excrete
the mineral in the urine, should levels of the mineral
rise to toxic levels in the blood.
Resources
BOOKS

Brody, Tom. Nutritional Biochemistry. San Diego:
Academic Press, 1998.

Tom Brody, PhD

Preparation
Evaluation of a patient’s mineral levels requires a
blood sample, and the preparation of plasma or serum
from the blood sample. An overnight fast is usually
recommended as preparation prior to drawing the
blood and chemical analysis. The reason for this is
that any mineral present in the food consumed at
breakfast may artificially boost the plasma mineral
content beyond the normal fasting level, and thereby
mask a mineral deficiency. In some cases, red blood
cells are used for the mineral status assay.

Aftercare
The healthcare provider assesses the patient’s
response to mineral treatment. A positive response
confirms that the diagnosis was correct. Lack of
response indicates that the diagnosis was incorrect,
that the patient had failed to take the mineral supplement, or that a higher dose of mineral was needed. The
response to mineral treatment can be monitored by
chemical tests, by an examination of red blood cells or
white blood cells, or by physiological tests, depending
on the exact mineral deficiency.

Risks
There are few risks associated with mineral treatment. In treating emergency cases of hyponatremia,
hypokalemia, or hypocalcemia by intravenous injections, there exists a very real risk that giving too much
sodium, potassium, or calcium, can result in hypernatremia, hyperkalemia, or hypercalcemia, respectively.
Risk for toxicity is rare where treatment is by dietary
means. This is because the intestines act as a barrier,
and absorption of any mineral supplement is gradual.
The gradual passage of any mineral through the intestines, especially when the mineral supplement is taken
with food, allows the various organs of the body to
acquire the mineral. Gradual passage of the mineral
2448

Minnesota multiphasic
personality inventory (MMPI-2)
Definition
The
Minnesota
Multiphasic
Personality
Inventory (MMPI-2; MMPI-A) is a written psychological assessment, or test, used to diagnose mental
disorders.

Purpose
The MMPI is used to screen for personality and
psychosocial disorders in adults and adolescents. It is
also frequently administered as part of a neuropsychological test battery to evaluate cognitive functioning.

Precautions
The MMPI should be administered, scored, and
interpreted by a clinical professional trained in its use,
preferably a psychologist or psychiatrist. The MMPI
is only one element of psychological assessment, and
should never be used alone as the sole basis for a
diagnosis. A detailed history of the test subject and a
review of psychological, medical, educational, or other
relevant records are required to lay the groundwork
for interpreting the results of any psychological
measurement.
Cultural and language differences in the test subject may affect test performance and may result in
inaccurate MMPI results. The test administrator
should be informed before psychological testing
begins if the test taker is not fluent in English and/or
has a unique cultural background.

Description
The original MMPI was developed at the
University of Minnesota and introduced in 1942. The
GALE ENCYCLOPEDIA OF MEDICINE

Neuropsychological testing—Tests used to evaluate patients who have experienced a traumatic
brain injury, brain damage, or organic neurological
problems (e.g., dementia). It may also be used to
evaluate the progress of a patient who has undergone treatment or rehabilitation for a neurological
injury or illness.
Norms—Normative or mean score for a particular
age group.
Psychopathology—A mental disorder or illness,
such as schizophrenia, personality disorder, or
major depressive disorder.
Standardization—The process of determining
established norms and procedures for a test to
act as a standard reference point for future test
results.

The administrator should provide the test subject
with information on the nature of the test and its
intended use, complete standardized instructions to
taking the MMPI (including any time limits, and
information on the confidentiality of the results).

Normal results
The MMPI should be scored and interpreted by a
trained professional. When interpreting test results for
test subjects, the test administrator will review what
the test evaluates, its precision in evaluation and any
margins of error involved in scoring, and what the
individual scores mean in the context of overall
norms for the test and the background of the test
subject.
Resources
BOOKS

current standardized version for adults 18 and over,
the MMPI-2, was released in 1989, with a subsequent
revision of certain test elements in early 2001. The
MMPI-2 has 567 items, or questions, and takes
approximately 60 to 90 minutes to complete. There is
a short form of the test that is comprised of the first
370 items on the long-form MMPI-2. There is also a
version of the inventory for adolescents age 14 to 18,
the MMPI-A.

Graham, John R. MMPI-2: Assessing Personality and
Psychopathology. 3rd ed. New York: Oxford University
Press, 1999.
ORGANIZATIONS

ERIC Clearinghouse on Assessment and Evaluation. 1131
Shriver Laboratory Bldg 075, University of Maryland,
College Park, MD 20742. (800) 464-3742. <http://
www.ericae.net>.

Paula Anne Ford-Martin

The questions asked on the MMPI are designed to
evaluate the thoughts, emotions, attitudes, and behavioral traits that comprise personality. The results of
the test reflect an individual’s personality strengths
and weaknesses, and may identify certain disturbances
of personality (psychopathologies) or mental deficits
caused by neurological problems.

Minor tranquilizers see Antianxiety drugs

There are six validity scales and ten basic clinical
or personality scales scored in the MMPI-2, and a
number of supplementary scales and subscales that
may be used with the test. The validity scales are used
to determine whether the test results are actually
valid (i.e., if the test-taker was truthful, answered
cooperatively and not randomly) and to assess the
test-taker’s response style (i.e., cooperative, defensive). Each clinical scale uses a set or subset of
MMPI-2 questions to evaluate a specific personality
trait. The MMPI should always be administered
in a controlled environment by a psychologist or
other qualified mental health professional trained
in its use.

Minority health addresses the special medical
and/or health needs associated with specific ethnic
groups.

GALE ENCYCLOPEDIA OF MEDICINE

Minority health
Definition

Description
The United States, as well as many other countries, experiences cultural diversity. This poses specific
health issues that are specific to ethnic groups.
Additionally, the propensity for certain diseases or
illnesses is of concern in certain minority groups.
These specific health issues include infant mortality
rates, cancer, cardiovascular disease, diabetes, HIV
infection, and immunizations.
2449

Minority health

Preparation

KEY TERMS

Minority health

D R . A N T O N I A N O V E L L O (1944– )
years old, she suffered two blows that she would carry all of
her life. Her father, Antonio Coello, died, leaving her
mother, Ana Delia Flores Coello, to raise her children
alone until she later remarried Ramon Flores, an electrician. Novello was also diagnosed with a chronic condition
called congenital megacolon, an illness in which her colon
was overly large and not functioning properly, which
required regular hospitalization. Although an operation
would have helped Novello, it was not performed until
she was 18 years old, and even after the surgery, complications followed her for years. Because of her childhood illness, Novello grew up wanting to be a doctor.

(Gamma Liaison. Reproduced by permission.)

Born Antonia Coello was born in Fajardo, Puerto Rico,
on August 23, 1944, the oldest of three children. At eight

Infant mortality rates
Infant mortality rates (IMRs) in the United States
and in all countries worldwide are an accurate indicator of health status. They provide information concerning programs about pregnancy education and
counseling, technological advances, and procedures
and aftercare. IMRs vary among racial groups.
African Americans had an IMRs of 14.2 per 1,000
live births in 1996, approximately 2.5 times higher
than Caucasians. The IMRs among American
Native Indian groups varies greatly, with some communities possessing IMRs about two times more than
national rates. Additionally Hispanic IMRs (7.6 per
1,000 live births) are also diverse for separate groups,
since the IMRs for example among Puerto Ricans is
higher (8.9 per 1,000 live births).
Cancer
Cancer is a serious national, worldwide, and minority health concern. It is the second cause of death in
the United States, claiming over half a million lives
each year. Approximately 50% of persons who
develop cancer will die. There is great disparity
2450

On October 17, 1989, President George Bush officially
nominated Novello for Surgeon General. The fourteenth
United States Surgeon General, Novello, sworn in on
March 9, 1990, remarked that "the American dream is
well and alive . . . today the West Side Story comes to the
West Wing." Novello was the first woman and the first
Hispanic to be appointed Surgeon General of the United
States. Noted for her philosophy of "good science, good
sense" and for her approachability, Novello was dedicated
to the prevention of AIDS, substance abuse, and smoking, as
well as to the education of the American public. Her special
concerns were for women, children, and hispanics—
populations often overlooked by public health services.

among the cancer rates in minority groups. Across
genders, cancer death rates for African Americans
are 35% higher when compared to statistics for
Caucasians. The death rates for prostate cancer
(two times more) and lung cancer (27 times more) are
disproportionately higher when compared to
Caucasians. There are also gender differences among
ethnic groups and specific cancers. Lung cancers in
African American and Hawaiian men are evaluated
compared with Caucasian males. Vietnamese females
who live in the United States have five times more new
cases of cervical cancer when compared to Caucasian
women. Hispanic females also have a greater incidence
of cervical cancer than Caucasian females.
Additionally, Alaskan native men and women have a
greater propensity for cancers in the rectum and colon
than do Caucasians.
Cardiovascular disease
Cardiovascular disease is responsible for the
leading cause of disability and death rates about
equal to death from all other diseases combined.
Cardiovascular disease can affect the patient’s lifestyle
and function in addition to having an impact on family
GALE ENCYCLOPEDIA OF MEDICINE

Diabetes
Diabetes—a serious health problem in Americans
and ethnic groups—is the seventh leading cause of
death in the United States. The prevalence of diabetes
in African Americans is about 70% higher than
Caucasians.
HIV
HIV infection/AIDS is the most common cause of
death for all persons age 25 to 44 years old. Ethnic
groups account for 25% of the United States population and 54% of all AIDS cases. In addition to sexual
transmission there is an increase in HIV among ethnic
groups related to intravenous drug usage.
Immunizations
Immunization, the reduction of preventable disease by vaccination, was lower in 1996, but the there
has been a rapid increase in African Americans taking
vaccinations. The coverage for immunization among
African Americans and Hispanics for persons age 65
and over is currently below the general population.
This may increase the death rates due to respiratory
infections.

Causes and symptoms
IMRs are correlated with prenatal care. Women
who receive adequate prenatal care tend to have better
pregnancy outcomes when compared to little or no
care. Women who receive inadequate prenatal care
also have increased chances of delivering a very low
birth weight (VLBW) infant, which is linked to risk of
early death.
Cancer is related to several preventable lifestyle
choices. Tobacco use, diet, and exposure to sun (skin
cancer) can be prevented by lifestyle modifications.
Additionally many cancers can occur due to lack of
interest and/or lack of availability for screening and
educational programs.
GALE ENCYCLOPEDIA OF MEDICINE

Cardiovascular diseases are higher among persons with high blood cholesterol and high blood pressure. Certain lifestyle choices may increase the chance
for heart disease includes lack of exercise, overweight,
and cigarette smoking. Cardiovascular disease is
responsible for over 50% of the deaths in persons
with diabetes.
HIV occurs at a higher frequency among homosexuals (the number of African-American males who
have AIDS through sex with men has increased).
Additionally unprotected sexual intercourse and sharing used needles for IV drug injection are strongly
correlated with infection.
Vaccinations are an effective method of preventing
certain disease such as polio, tetanus, pertussis,
diphtheria, influenza, hepatitis b, and pneumococcal
infections. Approximately 90% of influenza related
mortality is associated with persons aged 65 and
older. This is mostly due to neglect of vaccinations.
About 45,000 adults each year die of diseases related
to hepatitis B, pneumococcal, and influenza infections.

Diagnosis
The diagnosis of VLBW is by weight. Infants who
weigh 1,500 g are at high risk for death. For cancer, the
diagnosis can be made through screening procedures
such as mammography (for breast cancer), PAP smear
(for cervical cancer), and lifestyle modifications such
as avoidance of sun, cigarette smoking, balanced diets,
and adequate nutrition. Other specific screening tests
(PSA, prostate surface antigen) are helpful for diagnosing prostate cancer. Cardiovascular diseases can be
detected by medical check-up. Blood pressure and
cholesterol levels can be measured. Obesity can be
diagnosed by assessing a persons weight relative to
height. Diabetes and its complications can be detected
by blood tests, in-depth eye examinations and studies
that assess the flow of blood through blood vessels in
legs. HIV can be detected through a careful history/
physical examination and analysis of blood using a
special test called a western blot. Infections caused
by lack of immunizations can either be detected by
careful physical examination and culturing the specific
microorganism in the laboratory.

Treatment
Treatment is directed at the primary causes(s)
that minorities have increased chances of developing
disease(s). Cancer may require treatment utilizing
surgery, radiotherapy, or chemotherapy. Cardiovascular diseases may require surgical procedures for
2451

Minority health

members. The financial costs are very high. Among
ethnic and racial groups cardiovascular disease is the
leading cause of death. Stroke is the leading cause of
cardiovascular related death, which occurs in higher
numbers for Asian-American males when compared
to Caucasian men. Mexican-American men and
women and African-American males have a higher
incidence of hypertension. African-American women
have higher rates of being overweight, which is a major
risk factor of cardiovascular disease.

Minoxidil

KEY TERMS
Prevalence—Number of existing cases relative to
time.
Propensity—A greater risk for developing a
disease.

establishing a diagnosis and initiating treatment.
Depending on the extent of disease cardiovascular
management can become complicated requiring medications and daily lifestyle modifications. Treatment
usually includes medications, dietary modifications,
and—if complications arise—specific interventions
tailored to alleviating the problem. HIV can be treated
with specific medications and more often than not with
symptomatic treatment as reported complications
arise. Diseases caused by lack of immunizations are
treated based on the primary disease. The best method
of treatment is through prevention and generating
public awareness through educational awareness.

can be prevented by increasing awareness, interest,
and accessibility for prenatal care that address a
comprehensive approach for the needs of each patient.
Regular physicals and special screening tests ca potentially prevent certain cancers in high-risk groups.
Educational programs concerning lifestyle modifications, diet, exercise, and testing may prevent the
development of cardiovascular disease and diabetes.
Educational programs assemble to illicit IV drug
abusers and persons who engage in unprotected sexual
intercourse may decrease the incidence of HIV
infection.
Resources
ORGANIZATIONS

Office of Minority Health. 2001. <http://www.omhrc.gov/
rah/3rdpgBlue/Cardio/3pgGoalsCardio.htm>.

Laith Farid Gulli, M.D.
Nicole Mallory, M.S.

Alternative treatment
Alternative therapies do exist, but more research
is needed to substantiate present data. The diseases
that relate to minority health are best treated with
nationally accepted standards of care.

Prognosis
Generally the prognosis is related to the diagnosis,
patients state of health, age, and if there is another
disease or complication in addition to the presenting
problem. The course for IMRs is related to educational programs and prenatal care, which includes
medical and psychological treatments. The prognosis
for chronic diseases such as cardiovascular problems,
high blood pressure, cancer, and diabetes is variable.
These diseases are not cured and control is achieved by
standardized treatment options. Eventually complications, even with treatment can potentially occur. For
HIV the clinical course at present is death even though
this process may take years. Educational programs
with an emphasis on disease prevention can potentially improve outcomes concerning pediatric and
geriatric diseases.

Prevention
Prevention is accomplished best through educational programs specific to target populations. IMRs
2452

Minoxidil
Definition
Minoxidil is a drug available in two forms to treat
different conditions. Oral minoxidil is used to treat
high blood pressure and the topical solution form is
used to treat hair loss and baldness.

Purpose
Minoxidil was the first drug approved by the FDA
for the treatment of androgenetic alopecia (hair loss).
Before that, minoxidil had been used as vasodilator
drug prescribed as oral tablet to treat high blood
pressure, with side effects that included hair growth
and reversal of male baldness. In the 1980s, UpJohn
Corporation came out with a topical solution of 2%
minoxidil, called Rogaine, for the specific treatment of
androgenetic alopecia. Since the 1990s, numerous generic forms of minoxidil have become available to treat
hair loss while the oral form is still used to treat high
blood pressure.
The popularity hair loss treatment is due to the
general preference in the overall population for the
cosmetic appearance of a full head of hair. Minoxidil
is used to stimulate hair growth in areas of the scalp
that have stopped growing hair. As of early 2001, the
exact mechanism of action of minoxidil is not known.
GALE ENCYCLOPEDIA OF MEDICINE

People who have had a prior unusual or allergic
reaction to either minoxidil or propylene glycol, a nonactive chemical in the Rogaine solution, should not
use topical minoxidil. People who have had a previous
allergic reaction to preservatives or dyes may also be at
risk for having an allergic reaction to minoxidil.
People who are using cortisone, or cortisone-like
drugs (corticosteroids), petroleum jelly (Vaseline), or
tretinoin (Retin-A) on their scalps should consult their
doctors prior to using minoxidil. The use of any of
these products in conjunction with minoxidil may
cause excessive minoxidil absorption into the body
and increase the risk of side effects.
Also, people who have skin problems or irritations of the scalp, including sunburn, may absorb too
much minoxidil and increase their risk of side effects.
As for oral minoxidil, the form prescribed for high
blood pressure, patients should use minoxidil only
under medical supervision to ensure that excessive
amounts of the drug are not absorbed into their bodies.
Large amounts of minoxidil may increase the severity
of the symptoms and side effects of hypertension.
Minoxidil may pass from mother to child through
breast milk. Therefore, women who are breastfeeding
should not use minoxidil.

Description
For the treatment of hair loss, minoxidil is
available as a topical solution that is generally either
2% or 5% minoxidil in propylene glycol. The propylene glycol ensures that the applied minoxidil is evenly
spread across the affected area and easily absorbed
through the skin. As of early 2001, the 5% solution
is only approved by the FDA for use on men.
Approximately 1 milliliter of minoxidil solution is
applied to the scalp once a day using the fingertips or
a pump spray. It should be applied from the center of
the area being treated outward.
In the treatment of high blood pressure, oral minoxidil is usually prescribed when other medications
have failed to treat the condition. Dosage is usually
2.5-100 mg per day as a single dose for adults and
200 micrograms to 1 mg per kg of body weight for
children.

Preparation
Before using topical minoxidil, the hair and scalp
should be clean and dry before the minoxidil solution
is applied.
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
Hands, and any other areas of the body where hair
growth is not desired that may have come into contact
with topical minoxidil, should be washed immediately
after applying the minoxidil solution on the scalp.
Once applied, topical minoxidil should be allowed to
air-dry for at least two to four hours before clothing
are pulled on or off over the head, a hat is worn, or the
patient goes to bed. Prior to this, the minoxidil solution may stain clothing, hats, or bed linens; or, it may
be accidentally transferred from the patient’s head to
one of these objects, then back to other parts of the
patient’s body where hair growth is not desired.
A blow dryer, or other drying methods, should not
be used to speed the drying of the minoxidil as this may
interfere with the absorption of the medicine. People
using minoxidil should also not shampoo, wash, or
rinse their hair for at least 4 hours after minoxidil is
applied.

Risks
The most common side effects of topical minoxidil
use are itching and skin irritation of the treated area of
the scalp. Unwanted hair growth may also occur adjacent to treated areas or in areas where the medicine
has been inadvertently transferred several times. This
unwanted hair growth adjacent to the treatment area
may be particularly distressing to women when the
face is involved. The itching and irritation usually
subside after the drug has been used for approximately
two weeks. If symptoms persist after this time, minoxidil use should be halted until a physician has been
consulted.
Extremely rare side effects that may occur if too
much topically or orally administered minoxidil is
being absorbed in the body include:


changes in vision, most commonly blurred vision



chest pain



very low blood pressure



decreased sexual desire



fast or irregular heartbeat



flushing of the skin



headache



lightheadedness



numbness or tingling in the hands, feet, or face



partial, or complete, impotence



rapid weight gain



swelling of the hands, feet, lower legs, or face
2453

Minoxidil

Precautions

Miscarriage

KEY TERMS
Androgenetic alopecia—Hair loss that develops
into baldness and affects both men and women.
Hypertension—Persistently high arterial blood
pressure.
Scalp—That part of the head that is usually covered
with hair.
Topical drug—Drug or medication applied to a
specific area of the skin and affecting only the
area to which it is applied.
Vasodilation—The increase in the diameter of a
blood vessel resulting from relaxation of smooth
muscle within the wall of the vessel. Vasodilation
activates the blood flow.

90 days of stopping the medication and no further hair
growth will occur.
Resources
PERIODICALS

Bowser, Andrew. ‘‘Treatments Abound for Female Hair
Loss.’’ Dermatology Times June 1999.
Scow, Dean Thomas. ‘‘Medical Treatments for Balding in
Men.’’ American Family Physician April 15, 1999.
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, PO Box 4014, Schaumburg, IL 60168-4014. (847)
330-0230. Fax: 847-330-0050. <http://www.aad.org/>.
American Hair Loss Council. 30 Grassy Plain Road, Bethel,
CT 06801. (888) 873-9719. <http://www.ahlc.org/>.

Paul A. Johnson, Ed.M.

Vasodilators—Drugs or substances that cause
vasodilation.

Normal results
Topical minoxidil is much more effective at treating baldness that occurs on the top, or crown, of the
head than it is at causing hair growth on other parts of
the head. Minoxidil does not work for everyone and
there is no predictor, in early 2001, of whether or not it
will be effective in any particular person. Clinical tests
on the effectiveness of topical minoxidil in men with
baldness on the top of the head showed that 48% of
men who had used minoxidil for one year reported
moderate to dense re-growth of hair within the treated
area. Thirty-six percent reported minimal re-growth.
While 16% reported no re-growth. Similar percentages have been reported in women.
In both men and women, hair re-growth generally
does not begin until the medicine has been used for at
least four months. The first signs that minoxidil may
be effective in a particular person usually occur after
approximately 90 days of treatment, when the patient
notices that he or she is losing (shedding) much less
hair than prior to beginning treatment.
When new growth begins, the first hairs may be
soft and barely visible. For some patients, this is the
extent to the effectiveness of this medication. For
others, this down-like hair develops into hair of the
same color and thickness as the other hairs on their
heads.
Minoxidil is a treatment for hair loss, it is not a
cure. Once a patient stops taking minoxidil, he or she
will most likely lose all of the re-grown hair within
2454

Miscarriage
Definition
Miscarriage means loss of an embryo or fetus
before the 20th week of pregnancy. Most miscarriages
occur during the first 14 weeks of pregnancy. The
medical term for miscarriage is spontaneous abortion.

Description
Miscarriages are very common. Approximately
20% of pregnancies (one in five) end in miscarriage.
The most common cause is a genetic abnormality of
the fetus. Not all women realize that they are miscarrying and others may not seek medical care when it
occurs.
A miscarriage is often a traumatic event for both
partners, and can cause feelings similar to the loss of a
child or other member of the family. Fortunately, 90%
of women who have had one miscarriage subsequently
have a normal pregnancy and healthy baby; 60% are
able to have a healthy baby after two miscarriages.
Even a woman who has had three miscarriages in a
row still has more than a 50% chance of having a
successful pregnancy the fourth time.

Causes and symptoms
There are many reasons why a woman’s pregnancy ends in miscarriage. Often the cause is not
clear. However, more than half the miscarriages that
occur in the first eight weeks of pregnancy involve
GALE ENCYCLOPEDIA OF MEDICINE

In about 17% of cases, miscarriage is caused by an
abnormal hormonal imbalance that interferes with the
ability of the uterus to support the growing embryo.
This is known as luteal phase defect. In another 10%
of cases, there is a problem with the structure of the
uterus or cervix. This can especially occur in women
whose mothers used diethylstilbestrol (DES) when
pregnant with them.
The risk of miscarriage is increased by:


Smoking (up to a 50% increased risk)



Infection



Exposure to toxins (such as arsenic, lead, formaldehyde, benzene, and ethylene oxide)



Multiple pregnancy



Poorly-controlled diabetes.

The most common symptom of miscarriage is
bleeding from the vagina, which may be light or
heavy. However, bleeding during early pregnancy is
common and is not always serious. Many women have
slight vaginal bleeding after the egg implants in the
uterus (about 7-10 days after conception), which can
be mistaken for a threatened miscarriage. A few
women bleed at the time of their monthly periods
through the pregnancy. However, any bleeding in the
first three months of pregnancy (first trimester) is
considered a threat of miscarriage.
Women should not ignore vaginal bleeding during
early pregnancy. In addition to signaling a threatened
miscarriage, it could also indicate a potentially lifethreatening condition known as ectopic pregnancy. In
an ectopic pregnancy, the fetus implants at a site other
than the inside of the uterus. Most often this occurs in
the fallopian tube.
Cramping is another common sign of a possible
miscarriage. The cramping occurs because the uterus
attempts to push out the pregnancy tissue. If a pregnant woman experiences both bleeding and cramping
the possibility of miscarriage is more likely than if only
one of these symptoms is present.
If a woman experiences any sign of impending
miscarriage, she should be examined by a practitioner.
The doctor or nurse will perform a pelvic exam to
check if the cervix is closed as it should be. If the cervix
is open, miscarriage is inevitable and nothing can
GALE ENCYCLOPEDIA OF MEDICINE

preserve the pregnancy. Symptoms of an inevitable
miscarriage may include dull relentless or sharp intermittent pain in the lower abdomen or back. Bleeding
may be heavy. Clotted material and tissue (the
placenta and embryo) may pass from the vagina.
A situation in which only some of the products in
the uterus have been expelled is called an incomplete
miscarriage. Pain and bleeding may continue and
become severe. An incomplete miscarriage requires
medical attention.
A ‘‘missed abortion’’ occurs when the fetus has
died but neither the fetus nor placenta is expelled.
There may not be any bleeding or pain, but the symptoms of pregnancy will disappear. The physician may
suspect a missed abortion if the uterus does not continue to grow. The physician will diagnose a missed
abortion with an ultrasound examination.
A woman should contact her doctor if she experiences any of the following:


Any bleeding during pregnancy.



Pain or cramps during pregnancy.



Passing of tissue.



Fever and chills during or after miscarriage.

Diagnosis
If a woman experiences any sign of impending
miscarriage she should see a doctor or nurse for a
pelvic examination to check if the cervix is closed, as
it should be. If the cervix is open, miscarriage is
inevitable.
An ultrasound examination can confirm a missed
abortion if the uterus has shrunk and the patient has
had continual spotting with no other symptoms.

Treatment
Threatened miscarriage
For women who experience bleeding and cramping, bed rest is often ordered until symptoms disappear.
Women should not have sex until the outcome of the
threatened miscarriage is determined. If bleeding and
cramping are severe, women should drink fluids only.
Miscarriage
Although it may be psychologically difficult, if a
woman has a miscarriage at home she should try to
collect any material she passes in a clean container for
analysis in a laboratory. This may help determine why
the miscarriage occurred.
2455

Miscarriage

serious chromosomal abnormalities or birth defects
that would make it impossible for the baby to survive.
These are different from inherited genetic diseases.
They probably occur during development of the specific egg or sperm, and therefore are not likely to occur
again.

Mitral valve insufficiency

An incomplete miscarriage or missed abortion
may require the removal of the fetus and placenta by
a D&C (dilatation and curettage). In this procedure the
contents of the uterus are scraped out. It is performed
in the doctor’s office or hospital.
After miscarriage, a doctor may prescribe rest or
antibiotics for infection. There will be some bleeding
from the vagina for several days to two weeks after
miscarriage. To give the cervix time to close and avoid
possible infection, women should not use tampons or
have sex for at least two weeks. Couples should wait
for one to three normal menstrual cycles before trying
to get pregnant again.

Prognosis

KEY TERMS
Diethylstilbestrol (DES)—This is a synthetic estrogen drug that is used to treat a number of hormonal
conditions. However, it causes problems in developing fetuses and should not be taken during
pregnancy. From about 1938 to 1971, DES was
given to pregnant women because it was thought
to prevent miscarriage. Children of women who
took the drug during pregnancy are at risk for
certain health problems.
Dilation and curettage (D&C)—A procedure in
which the neck of the womb (cervix) is expanded
and the lining of the uterus is scraped to remove
pregnancy tissue or abnormal tissue.

A miscarriage that is properly treated is not lifethreatening, and usually does not affect a woman’s
ability to deliver a healthy baby in the future.

Embryo—An unborn child in the first eight weeks
after conception. After the eighth week until birth,
the baby is called a fetus.

Feelings of grief and loss after a miscarriage are
common. In fact, some women who experience a miscarriage suffer from major depression during the six
months after the loss. This is especially true for women
who don’t have any children or who have had depression in the past. The emotional crisis can be similar to
that of a woman whose baby has died after birth.

Hygeia Foundation, Inc. P.O. Box 3943 New Haven, CT
06525. (203) 387-3589. <http://www.hygeia.org>.

Prevention
The majority of miscarriages cannot be prevented
because they are caused by severe genetic problems
determined at conception. Some doctors advise
women who have a threatened miscarriage to rest in
bed for a day and avoid sex for a few weeks after the
bleeding stops. Other experts believe that a healthy
woman (especially early in the pregnancy) should continue normal activities instead of protecting a pregnancy that may end in miscarriage later on, causing
even more profound distress.
If miscarriage was caused by a hormonal imbalance (luteal phase defect), this can be treated with a
hormone called progesterone to help prevent subsequent miscarriages. If structural problems have led to
repeated miscarriage, there are some possible procedures to treat these problems. Other possible ways to
prevent miscarriage are to treat genital infections, eat
a well-balanced diet, and refrain from smoking and
using recreational drugs.
Resources
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th Street, S.W., P.O. Box 96920.

2456

Carol A. Turkington

Mitral incompetence see Mitral valve
insufficiency
Mitral regurgitation see Mitral valve
insufficiency
Mitral stenosis see Mitral valve stenosis

Mitral valve insufficiency
Definition
Mitral valve insufficiency is a term used when the
valve between the upper left chamber of the heart
(atrium) and the lower left chamber (ventricle) does
not close well enough to prevent back flow of blood
when the ventricle contracts. Mitral valve insufficiency
is also known as mitral valve regurgitation or mitral
valve incompetence.

Description
Normally, blood enters the left atrium of the heart
from the lungs and is pumped through the mitral valve
into the left ventricle. The left ventricle contracts to
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Aorta—A large artery beginning at the base of the
left ventricle.
Atrium—One of the two upper chambers of the
heart.
Rheumatic fever—An illness that sometimes follows a streptococcal infection of the throat.
Ventricle—One of the two lower chambers of the
heart.

Causes and symptoms
In the past, rheumatic fever was the most common
cause of mitral valve insufficiency. However, the
increased use of antibiotics for strep throat has made
rheumatic fever rare in developed countries. In these
countries, mitral valve insufficiency caused by rheumatic fever is seen mostly in the elderly. In countries
with less developed health care, rheumatic fever is
still common and is often a cause of mitral valve
insufficiency.
Heart attacks that damage the structures that support the mitral valve are a common cause of mitral
valve insufficiency. Myxomatous degeneration can
cause a ‘‘floppy’’ mitral valve that leaks. In other
cases, the valve simply deteriorates with age and
becomes less efficient.
People with mitral valve insufficiency may not
have any symptoms at all. It is often discovered during
a doctor’s visit when the doctor listens to the heart
sounds.
Both the left atrium and left ventricle tend to get a
little bigger when the mitral valve does not work properly. The ventricle has to pump more blood so it gets
bigger to increase the force of each beat. The atrium
gets bigger to hold the extra blood. An enlarged ventricle can cause palpitations. An enlarged atrium can
develop an erratic rhythm (atrial fibrillation), which
reduces its efficiency and can lead to blood clots forming in the atrium.

Diagnosis
When the doctor listens to the heart sounds,
mitral valve insufficiency is generally recognized by
the sound the blood makes as it leaks backward. It
sounds like a regurgitant murmur. The next step is
generally a chest x ray and an electrocardiogram
(ECG) to see if the heart is enlarged. The most definitive noninvasive test is echocardiography, a test that
uses sound waves to make an image of the heart. This
GALE ENCYCLOPEDIA OF MEDICINE

test gives a picture of the valve in action and shows the
severity of the problem.

Treatment
A severely impaired valve needs to be repaired or
replaced. Either option will require surgery. Repairing
the valve can fix the problem completely or reduce it
enough to make it bearable and prevent damage to the
heart. Valves can be replaced with either a mechanical
valve or one that is partly mechanical and partly from
a pig’s heart.
Mechanical valves are effective but can increase
the incidence of blood clots. To prevent blood clots
from forming, the patient will need to take drugs that
prevent abnormal blood clotting (anticoagulants).
The valves made partly from a pigs heart do not have
as great a risk of blood clots but don’t last as long as
fully mechanical valves. If a valve wears out, it must be
replaced again.
Damaged heart valves are easily infected.
Anytime a procedure is contemplated that might
allow infectious organisms to enter the blood, the
person with mitral valve insufficiency should take
antibiotics to prevent possible infection.

Prognosis
The diagnostic, medical and surgical procedures
available to the person with mitral valve insufficiency
are all likely to produce good results.

Prevention
The only possible way to prevent mitral valve
insufficiency is to prevent rheumatic fever. This can
be done by evaluating sore throats for the presence of
the bacteria that causes strep throat. Strep throat is
easily treated with antibiotics.
2457

Mitral valve insufficiency

pump the blood forward into the aorta. The aorta is
a large artery that sends oxygenated blood through
the circulatory system to all of the tissues in the body.
If the mitral valve is leaky due to mitral valve insufficiency, it allows some blood to get pushed back
into the atrium. This extra blood creates an increase
in pressure in the atrium, which then increases
blood pressure in the vessels that bring the blood
from the lungs to the heart. Increased pressure in
these vessels can result in increased fluid buildup in
the lungs.

Mitral valve prolapse

Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

pass out. Some persons may experience difficulty
breathing, ankle swelling and fluid in the lungs.
Other symptoms may include anxiety, headaches,
morning tiredness and constantly cold hands and
feet. Death from this condition is rare.

OTHER

The Meck Page. <http://www.merck.com>.

Dorothy Elinor Stonely

Mitral valve prolapse
Definition
Mitral valve prolapse (MVP) is a ballooning of the
support structures of the mitral heart valve into the left
upper collection chamber of the heart.

Description
Other names for MVP include floppy valve and
Barlow’s syndrome. The mitral valve is located on the
left side of the heart between the top chamber (left
atrium) and the bottom chamber (left ventricle). The
valve opens and closes according to the heartbeat and
the pressure that is exerted upon it from the blood in
both chambers.
The valve has supporting structures that attach to
the heart muscle to help it open and close properly.
When these structures weaken or lengthen abnormally, the valve may balloon into the left atrium.
Sometimes this can cause the mitral valve to leak
blood backward.
This condition may be inherited and occurs in
approximately 10% of the population. It affects
more women than men and often peaks after the age
of 40.

Causes and symptoms
MVP may occur due to rheumatic heart disease
but is usually found in healthy people. Changes that
occur in the valve are caused by rapid multiplication of
cells in the middle layer that presses on the outer layer.
The outer layer weakens, causing a prolapse of the
valve toward the left atrium.
Most persons do not have symptoms. Those that
do may experience sharp, left-sided chest pain. Some
complain of fatigue, or a pounding feeling in the chest.
Others can have an irregular heart beat and even
2458

Diagnosis
The diagnosis of MVP is based on symptoms and
physical exam. During the exam, the physician may
hear a click and/or heart murmur with a stethoscope.
The best diagnostic test for MVP is the echocardiogram. The test reflects sound waves through the
chest wall to give two-dimensional color flow pictures
of the heart, its size, position, motion, chambers, and
valves. Unfortunately, during the early 1980s, this
diagnosis was often made excessively from faulty
echocardiographic criteria prevalent at that time.
Any person with symptoms or family history of
MVP should consider having an echocardiogram.
The test takes 15-20 minutes and is done in doctor’s
offices and hospitals. It is performed by trained
technicians and is read by cardiologists. Family
physicians, internists, cardiologists, and nurse
practitioners can treat MVP. Echocardiograms are
recommended periodically depending on the extent
of valve leakage.

Treatment
Persons who experience certain types of an irregular heartbeat with MVP should be treated.
Propranolol (Inderal) or other beta blockers or
digoxin (Lanoxin) are often helpful. Persons who
develop moderate to severe symptoms with a leaky
mitral valve may require repair or replacement of the
mitral valve with an artificial heart valve. Persons with
MVP and a leaky valve need to protect themselves
from heart or heart valve infections. Antibiotics
should be taken before any surgical, dental or oral
procedures according to the American Heart
Association recommendations.
Other treatments include drinking lots of fluids
during strenuous activity and hot weather. Water pills,
caffeine and donating blood may aggravate the symptoms of MVP.

Prognosis
MVP is usually not a serious condition. However,
dangerous, untreated irregular heartbeats may rarely
cause sudden death. These persons should be carefully
monitored.
GALE ENCYCLOPEDIA OF MEDICINE

Mitral valve stenosis

Mitral valve prolapse

Mitral valve stenosis

Mitral valve prolapse occurs when the mitral valve does not open and close properly. When this happens, the valve may balloon
into the left atrium of the heart, causing the mitral valve to leak blood backward. Mitral valve stenosis refers to the narrowing of
the mitral valve, in which the flow of blood from the atrium to the ventricle becomes restricted. (Illustration by Electronic Illustrators
Group.)

become narrow and restricts the flow of blood from
the upper left chamber (left atrium) to the lower left
chamber (left ventricle).

KEY TERMS
Heart murmur—Sound during the heartbeat
caused by a heart valve that does not close
properly.
Rheumatic heart disease—A condition caused by a
streptococcus infection which can result in permanent heart damage.

Resources
PERIODICALS

McGrath, Dicey. ‘‘Mitral Valve Prolapse.’’ American
Journal of Nursing May 1997: 40-41.

Lisa Papp, RN

Mitral valve stenosis
Definition
The term stenosis means an abnormal narrowing
of an opening. Mitral valve stenosis refers to a condition in the heart in which one of the valve openings has
GALE ENCYCLOPEDIA OF MEDICINE

Description
In the heart, the valve that regulates the flow of
blood between the left atrium and the left ventricle is
called the mitral valve. If the mitral valve is abnormally narrow, due to disease or birth defect, blood
flow from the atrium to the ventricle is restricted.
This restricted flow leads to an increase in the pressure
of blood in the left atrium. Over a period of time, this
back pressure causes fluid to leak into the lungs. It can
also lead to an abnormal heart rhythm (atrial fibrillation), which further decreases the efficiency of the
pumping action of the heart.

Causes and symptoms
Mitral valve stenosis is almost always caused by
rheumatic fever. As a result of rheumatic fever, the
leaflets that form the opening of the valve are partially
fused together. Mitral valve stenosis can also be present at birth. Babies born with this problem usually
require surgery if they are to survive. Sometimes,
growths or tumors can block the mitral valve, mimicking mitral valve stenosis.
If the restriction is severe, the increased blood
pressure can lead to heart failure. The first symptoms
2459

Moles

of heart failure, which are fatigue and shortness of
breath, usually appear only during physical activity.
As the condition gets worse, symptoms may also be
felt even during rest. A person may also develop a deep
red coloring in the cheeks.

Diagnosis
Mitral valve stenosis is usually detected by a physician listening to heart sounds. Normal heart valves
open silently to permit the flow of blood. A stenotic
valve makes a snapping sound followed by a ‘‘rumbling’’ murmur. The condition can be confirmed with
a chest x ray and an electrocardiogram, both of which
will show an enlarged atrium. Echocardiography,
which produces images of the heart’s structure, is
also helpful in making the diagnosis. If surgery is
necessary, cardiac catheterization may be done to
fully evaluate the heart before the operation.

Treatment
Drug therapy may help to slow the heart rate,
strengthen the heart beat, and control abnormal heart
rhythm. Drugs such as beta blockers, calcium channel
blockers, and digoxin may be prescribed. A drug that
prevents abnormal blood clotting (anticoagulant)
called warfarin (Coumadin) may be recommended. If
drug therapy does not produce satisfactory results,
valve repair or replacement may be necessary.
Repair can be accomplished in two ways. In the
first method, balloon valvuloplasty, the doctor will try
to stretch the valve opening by threading a thin tube
(catheter) with a balloon tip through a vein and into
the heart. Once the catheter is positioned in the valve,
the balloon is inflated, separating the fused areas. The
second method involves opening the heart and surgically separating the fused areas.
If the valve is damaged beyond repair, it can be
replaced with a mechanical valve or one that is partly
mechanical and partly made from a pig’s heart.

Prognosis
Procedures available to treat mitral valve stenosis,
whether medical or surgical, all produce effective
results.

Prevention
The only possible way to prevent mitral valve
stenosis is to prevent rheumatic fever. This can be
done by evaluating sore throats for the presence of
2460

KEY TERMS
Atrium—One of the two upper chambers of the
heart.
Beta blocker—A drug that can be used to reduce
blood pressure.
Rheumatic fever—An illness which sometimes follows a streptococcal infection of the throat.
Ventricle—One of the two lower chambers of the
heart.

the bacteria that causes strep throat. Strep throat is
easily treated with antibiotics.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
OTHER

The Meck Page. <http://www.merck.com>.

Dorothy Elinor Stonely

Molar pregnancy see Hydatidiform mole

Moles
Definition
A mole (nevus) is a pigmented (colored) spot on
the outer layer of the skin (epidermis).

Description
Moles can be round, oval, flat, or raised. They can
occur singly or in clusters on any part of the body.
Most moles are brown, but colors can range from
pinkish flesh tones to yellow, dark blue, or black.
Everyone has at least a few moles. They generally
appear by the time a person is 20 and resemble freckles
at first. A mole’s color and shape don’t usually change.
Changes in hormone levels that occur during puberty
and pregnancy can make moles larger and darker. New
moles may also appear during this period.
A mole usually lasts about 50 years before beginning to fade. Some moles disappear completely, and
GALE ENCYCLOPEDIA OF MEDICINE

combination of other inherited traits and environmental factors.

Diagnosis
Types of moles
About 1–3% of all babies have one or more moles
when they are born. Moles that are present at birth are
called congenital nevi.
Other types of moles include:


Junctional moles, which are usually brown and may
be flat or slightly raised.



Compound moles, which are slightly raised, range in
color from tan to dark brown, and involve pigmentproducing cells (melanocytes) in both the upper and
lower layers of the skin (epidermis and dermis).



Dermal moles, which range from flesh-color to
brown, are elevated, most common on the upper
body, and may contain hairs.



Sebaceous moles, which are produced by over-active
oil glands and are yellow and rough-textured.



Blue moles, which are slightly raised, colored by
pigment deep within the skin, and most common on
the head, neck, and arms of women.

Most moles are benign, but atypical moles (dysplastic nevi) may develop into malignant melanoma, a
potentially fatal form of skin cancer. Atypical moles
are usually hereditary. Most are bigger than a pencil
eraser, and the shape and pigmentation are irregular.
Congenital nevi are more apt to become cancerous than moles that develop after birth, especially if
they are more than eight inches in diameter. Lentigo
maligna (melanotic freckle of Hutchinson), most common on the face and after the age of 50, first appears as
a flat spot containing two or more shades of tan. It
gradually becomes larger and darker. One in three of
these moles develop into a form of skin cancer known
as lentigo maligna melanoma.

Causes and symptoms
The cause of moles is unknown, although atypical
moles seem to run in families and result from exposure
to sunlight.
In the past several years, researchers have identified two genes known as CDKN2A and CDK4 that
govern susceptibility to melanoma in humans. Other
susceptibility genes are being sought as of early 2003.
Most experts, however, think that these susceptibility
genes are not sufficient by themselves to account for
moles becoming cancerous but are influenced by a
GALE ENCYCLOPEDIA OF MEDICINE

Only a small percentage of moles require medical
attention. A mole that has the following symptoms
should be evaluated by a dermatologist (a physician
spealizing in skin diseases).


Appears after the age of 20



Bleeds



Itches



Looks unusual or changes in any way.

A doctor who suspects skin cancer will remove all
or part of the mole for microscopic examination. This
procedure, which is usually performed in a doctor’s
office, is simple, relatively painless, and does not take
more than a few minutes. It does leave a scar.
The doctor may also use a dermatoscope to examine the mole prior to removal. The dermatoscope,
which can be used to distinguish between benign
moles and melanomas, is an instrument that resembles
an ophthalmoscope. An immersion oil is first applied to
the mole to make the outer layers of skin transparent.
A combination of high-frequency ultrasound and
color Doppler studies has also been shown to have a
high degree of accuracy in distinguishing between
melanomas and benign moles.

Treatment
If laboratory analysis confirms that a mole is cancerous, the dermatologist will remove the rest of the
mole. Patients should realize that slicing off a section
of a malignant mole will not cause the cancer to spread.
Removing a mole for cosmetic reasons involves
numbing the area and using scissors or a scalpel to
remove the elevated portion. The patient is left with a
flat mole the same color as the original growth. Cutting
out parts of the mole above and beneath the surface of
the skin can leave a scar more noticeable than the mole.
Scissors or a razor can be used to temporarily
remove hair from a mole. Permanent hair removal,
however, requires electrolysis or surgical removal of
the mole.

Prognosis
Moles are rarely cancerous and, once removed,
unlikely to recur. A dermatologist should be consulted
if a mole reappears after being removed.
2461

Moles

some never lighten at all. Some moles develop stalks
that raise them above the skin’s surface; these moles
eventually drop off.

Moles
Woman’s birthmark being removed by laser. (Photograph by Alexander Tsiaras, Photo Researchers, Inc. Reproduced by permission.)

Prevention

KEY TERMS

Wearing a sunscreen and limiting sun exposure
may prevent some moles. Anyone who has moles
should examine them every month and see a dermatologist if changes in size, shape, color, or texture
occur or if new moles appear.

Dermatology—The branch of medicine that studies and treats disorders of the skin.
Malignant melanoma—A potentially fatal form of
skin cancer that develops from melanocytes, which
are skin cells containing melanin.

A team of researchers at Duke University
reported in 2003 that topical application of a combination of 15% vitamin C and 1% vitamin E over a
four-day period offered significant protection against
sunburn. The researchers suggest that this combination
may protect skin against aging caused by sunlight as
well.
Anyone with a family history of melanoma should
see a dermatologist for an annual skin examination.
Everyone should know the ABCDEs of melanoma:


A: Asymmetry, which occurs when the two halves of
the mole are not identical



B: Borders that are irregular or indistinct



C: Color that varies in a single mole

2462

Melanin—A dark insoluble pigment found in
humans in the skin, hair, choroid layer of the eye,
and a part of the brain called the substantia nigra.
Nevus (plural, nevi)—The medical term for any
anomaly of the skin that is present at birth, including moles and birthmarks.



D: Diameter, which should be no larger than a pencil
eraser (about 6 mm)



E: Elevated above the surrounding tissue.

A mole with any of these characteristics should be
evaluated by a dermatologist.
GALE ENCYCLOPEDIA OF MEDICINE

Nevus Outreach, Inc. 1601 Madison Blvd., Bartesville, OK
74006. (877) 426-3887. <http://www.nevus.org>.

Maureen Haggerty
Rebecca J. Frey, PhD

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Dermatologic Disorders: Malignant Tumors.’’
Section 10, Chapter 126. In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Dermatologic Disorders: Moles.’’ Section 10, Chapter
125. In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Dermatologic Disorders: Reactions to Sunlight.’’
Section 10, Chapter 119. In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Bennett, D. C. ‘‘Human Melanocyte Senescence and
Melanoma Susceptibility Genes.’’ Oncogene 22 (May
19, 2003): 3063–3069.
Bessoud, B., N. Lassau, S. Koscielny, et al. ‘‘HighFrequency Sonography and Color Doppler in the
Management of Pigmented Skin Lesions.’’ Ultra sound
in Medicine & Biology 6 (June 2003): 875-879.
Bray, C. ‘‘The Development of an Improved Method of
Photography for Mole-Monitoring at the University
Hospital of North Durham.’’ Journal of Audiovisual
Media in Medicine 26 (June 2003): 60–66.
Hall, Daniel J., MD, and Michael Holtel, MD. ‘‘Malignant
Melanoma of the Face and Neck.’’ eMedicine July 3,
2003. <http://www.emedecine.com.ent/topic27.htm>.
Lin, J. Y., M. A. Selim, C. R. Shea, et al. ‘‘UV
Photoprotection by Combination Topical Antioxidants
Vitamin C and Vitamin E.’’ Journal of the American
Academy of Dermatology 48 (June 2003): 866-874.
Tucker, M. A., and A. M. Goldstein. ‘‘Melanoma Etiology:
Where Are We?’’ Oncogene 22 (May 19, 2003):
3042–3052.

Molybdenum excess see Mineral toxicity
Mometasone see Corticosteroids
Moncytic ehrlichiosis see Ehrlichiosis
Mongolism see Down syndrome
Moniliasis see Candidiasis

Monkeypox
Definition
Monkeypox is an infectious disease caused by an
orthopoxvirus. Orthopoxviruses are a genus of viruses
that include the disease agents that cause human
smallpox, cowpox, and camelpox as well as monkeypox. Monkeypox, which was first identified in humans
in an outbreak in Africa in 1970, usually produces a
less severe illness with fewer fatalities than smallpox.
However, its symptoms are similar: fever, pus-filled
blisters all over the body, and respiratory problems.
Monkeypox is classified as a zoonosis, which
means that it is a disease of animals that can be transmitted to humans under natural conditions. The first
cases of monkeypox reported in humans involved contact between humans and animals in the African rain
forest. The outbreak that made headlines in the
United States in June 2003, however, involved animals
purchased as pets from pet stores. In nature, monkeypox has been found in monkeys, chimpanzees, rabbits,
prairie dogs, Gambian rats, ground squirrels, and
mice. It is not known as of late 2003 whether other
wild or domestic animals can contract monkeypox.

ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800) ACS-2345.
National Cancer Institute (NCI). NCI Public Inquiries
Office, Suite 3036A, 6116 Executive Boulevard,
MSC8332, Bethesda, MD 20892-8322. (800)
4-CANCER or (800) 332-8615 (TTY).
<http://www.nci.nih.gov>.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Prior to 2003, most monkeypox cases were diagnosed in remote areas of central and west Africa.
Between February 1996 and October 1997, however,
there were 511 suspected cases of monkeypox in the
Democratic Republic of the Congo (DRC, formerly
Zaire). This outbreak, the largest ever, raised fears
that the virus had mutated and become more
infectious.
2463

Monkeypox

Advances in photographic technique have now
made it easier to track the development of moles
with the help of whole-body photographs. A growing
number of hospitals are offering these photographs as
part of outpatient mole-monitoring services.

Monkeypox

In late 1997, the U.S. Centers for Disease Control
and Prevention (CDC) and the World Health
Organization (WHO) announced that this relatively
large outbreak was likely due to human behavior,
rather than virus mutation. During the outbreak, the
DRC was embroiled in civil war. Food shortages
increased reliance on hunting and raised chances that
people would come into contact with infected animals.
The 2003 outbreak in the United States, which
was the first confirmed instance of communityacquired monkeypox in North America, came to the
attention of the CDC in early June, when a laboratory
in Wisconsin identified the monkeypox virus in samples taken from the skin of an infected patient and
lymph node tissue from the patient’s pet prairie dog.
By the end of June, cases of monkeypox in humans
had been identified in six Midwestern states (Illinois,
Indiana, Kansas, Missouri, Ohio, and Wisconsin).
The patients acquired the virus from infected prairie
dogs purchased as pets, which in turn were infected
through contact with animals imported from Africa
that were sold in the same pet stores.
Monkeypox is less severe than smallpox and can
sometimes be confused with chickenpox. It seems partly
preventable with smallpox vaccination, but vaccination
programs were discontinued in the late 1970s. (Barring
samples stored in laboratories, smallpox has been eradicated.) People under the age of 16—those born after
smallpox vaccination ended—seem the most susceptible to monkeypox. During the 1996-97 outbreak,
approximately 85% of the cases were in this age group.
Although the monkeypox virus is related to the
smallpox virus, experts do not think (as of late 2003)
that it is likely to be cultivated as an agent of bioterrorism.
Monkeypox is much less easily transmitted person-toperson than smallpox and has a much lower fatality rate.

Causes and symptoms
The monkeypox virus is transmitted to humans
through an infected animal’s blood, body sores, or
bite; or through handling an infected animal’s bedding
or cage. Initial symptoms of monkeypox in humans
include fever, a bodywide rash (exanthem) of pus-filled
blisters, and flu-like muscle aches and fatigue. These
symptoms can be accompanied by diarrhea, swollen
lymph nodes, a sore throat, and mouth sores. In some
cases, a victim may experience trouble breathing.
Symptoms are at their worst for 3–7 days, after which
the fever lessens and blisters begin to form crusts.
The symptoms of monkeypox in pet rabbits, rats,
or mice include inflammation of the eyes, a nasal
2464

discharge, fever, loss of appetite, a skin rash, and
tiredness. Pet monkeys typically develop a rash with
pus-filled lesions on the palms of the hands, trunk, and
tail. They may also have mouth ulcers.

Diagnosis
Since the symptoms of monkeypox resemble other
diseases caused by orthopox viruses, definitive diagnosis may require laboratory testing to uncover the
virus or evidence (from antibodies in the blood) that
it is present. As of 2003, laboratory techniques that
can be used to identify the monkeypox virus include
electron microscopy, polymerase chain reaction
(PCR), immunohistochemistry, and ELISA testing.

Treatment
Like most viruses, monkeypox cannot be resolved
with medication. The only treatment option is symptomatic—that is, patients are made as comfortable as
possible. In March 1998, the U.S. Army Medical
Research Institute for Infectious Diseases reported
that an antiviral drug called cidofovir may combat
monkeypox infection. As of 2003, additional studies
report that cidofovir appears to be safe and effective as
a treatment for monkeypox in humans.The drug has
worked successfully in primates, but further research
is needed to determine its effectiveness in humans.

Prognosis
Children are more likely to contract the disease
and have the highest death rate. Monkeypox is not as
lethal as smallpox, but the death rate among young
children may reach 2–10%. In some cases, hospitalization is required. Recovery is good among survivors,
although some scarring may result from the blisters.

Prevention
Monkeypox is one of the diseases that physicians,
veterinarians, and public health officials are required
by law to report to the CDC.
Although smallpox vaccination offers some protection against monkeypox, experts do not generally
recommend getting a smallpox vaccination simply to
guard against monkeypox if one has not been exposed
to it. However, the CDC recommends as of June 2003
that anyone who has had close contact with humans or
animals infected with monkeypox, or has helped to
care for them, should be vaccinated against smallpox.
The vaccination can be administered as late as 14 days
after exposure to the virus. In addition, veterinarians
GALE ENCYCLOPEDIA OF MEDICINE

Antiviral—Refers to a drug that can destroy viruses
and help treat illnesses caused by them.
Bioterrorism—The intentional use of diseasecausing microbes or other biologic agents to
intimidate or terrorize a civilian population for
political or military reasons.
Mutation—A change in an organism’s genetic code
that causes it to develop new characteristics.
Orthopoxvirus—The genus of viruses that includes
monkeypox, smallpox, cowpox, and camelpox.
Symptomatic—Refers to treatment that addresses
the symptoms of an illness, but not its underlying
cause.
Zoonosis (plural, zoonoses)—Any disease of animals that can be transmitted to humans under
natural conditions. Monkeypox is a zoonosis.

or public health personnel conducting field investigations should be vaccinated before any exposure to
monkeypox.
As of late 2003, no cases of monkeypox were
identified in cats or dogs belonging to people infected
by the June outbreak. The American Veterinary
Medicine Association (AVMA) recommends, however, that cats, dogs, or other mammals that have
been in contact with an animal known to have monkeypox should be kept in quarantine for 30 days from
the date of exposure.
People who have a pet with symptoms of monkeypox should not take it to an animal shelter or
release it into the wild. They should isolate it from
humans and other animals, and take it to a veterinarian in a closed, chew-proof container with air holes.

Wisconsin, 2003.’’ Morbidity and Mortality Weekly
Report 52 (June 13, 2003): 537–540.
Centers for Disease Control and Prevention. ‘‘Update:
Multistate Outbreak of Monkeypox—Illinois, Indiana,
Kansas, Missouri, Ohio, and Wisconsin, 2003.’’
Morbidity and Mortality Weekly Report 52 (June 20,
2003): 561–564.
Centers for Disease Control and Prevention. ‘‘Update:
Multistate Outbreak of Monkeypox—Illinois, Indiana,
Kansas, Missouri, Ohio, and Wisconsin, 2003.’’
Morbidity and Mortality Weekly Report 52 (June 27,
2003): 589–590.
Rosen, T., and J. Jablon. ‘‘Infectious Threats from Exotic
Pets: Dermatological Implications.’’ Dermatologic
Clinics 21 (April 2003): 229–236.
Smee, D. F., K. W. Bailey, and R. W. Sidwell. ‘‘Comparative
Effects of Cidofovir and Cyclic HPMPC on Lethal
Cowpox and Vaccinia Virus Respiratory Infections in
Mice.’’ Chemotherapy 49 (June 2003): 126–131.
ORGANIZATIONS

American Veterinary Medical Association (AVMA). 1931
North Meacham Road, Suite 100, Schaumburg, IL
60173-4360. <http://www.avma.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
OTHER

American Veterinary Medical Association (AVMA).
‘‘Foreign Animal Disease Alert: Investigation
Uncovers First Outbreak of Monkeypox Infection in
the Western Hemisphere,’’ June 23, 2003. <http://
www.avma.org/pubhlth/monkeypox/default.asp>.
American Veterinary Medical Association (AVMA).
Monkeypox Backgrounder. Schaumburg, IL: AVMA,
June 2003.
Centers for Disease Control and Prevention (CDC). Fact
Sheet: Basic Information About Monkeypox. Atlanta,
GA: CDC, June 2003.
Centers for Disease Control and Prevention (CDC). Fact
Sheet: Embargoed Animals and Monkeypox Virus.
Atlanta, GA: CDC, June 2003.

On June 11, 2003, the CDC and the Food and
Drug Administration (FDA) issued a joint order prohibiting the importation of rats and other rodents
from Africa. In addition, the agencies banned the
sale and distribution of prairie dogs and six species
of African rodents in the United States.

Julia Barrett
Rebecca J. Frey, PhD

Resources
PERIODICALS

Altman, Larry K., MD, and Jodi Wilgoren. ‘‘20 Cases of
Disease Related to Smallpox Detected in the U.S.’’ New
York Times June 9, 2003.
Centers for Disease Control and Prevention. ‘‘Multistate
Outbreak of Monkeypox—Illinois, Indiana, and
GALE ENCYCLOPEDIA OF MEDICINE

Monoamine oxidase inhibitors
Definition
Monoamine oxidase inhibitors (MAO inhibitors)
are medicines that relieve certain types of mental
depression.
2465

Monoamine oxidase inhibitors

KEY TERMS

Monoamine oxidase inhibitors

Purpose
MAO inhibitors are a type of antidepressant and
are used to treat mental depression. Like other antidepressant drugs, MAO inhibitors help reduce the
extreme sadness, hopelessness, and lack of interest in
life that are typical in people with depression. MAO
inhibitors are especially useful in treating people
whose depression is combined with other problems
such as anxiety, panic attacks, phobias, or the desire
to sleep too much.

Description
Discovered in the 1950s, MAO inhibitors work
by correcting chemical imbalances in the brain.
Normally, natural chemicals called neurotransmitters
carry signals from one brain cell to another. Some
neurotransmitters, such as serotonin and norepinephrine, play important roles in controlling mood.
But other substances in the brain may interfere with
mood control by breaking down these neurotransmitters. Researchers believe that MAO inhibitors work by
blocking the chemicals that break down serotonin and
norepinephrine. This gives the neurotransmitters more
time to do their important work.
Because MAO inhibitors also affect other chemicals throughout the body, these drugs may produce
many unwanted side effects. They can be especially
dangerous when taken with certain foods, beverages
and medicines. Anyone taking these drugs should ask
his or her physician or pharmacist for a list of products
to avoid.
MAO inhibitors are available only with a physician’s prescription. They are sold in tablet form. Some
commonly used MAO inhibitors are isocarboxazid
(Marplan), phenelzine (Nardil), and tranylcypromine
(Parnate).

Recommended dosage
The recommended dosage depends on the type of
MAO inhibitor and the type of depression for which it
is being taken. Dosages may be different for different
patients. Check with the physician who prescribed the
drug or the pharmacist who filled the prescription for
the correct dosage.
Always take MAO inhibitors exactly as directed
by your physician. Never take larger or more frequent
doses, and do not take the drug for longer than directed. See the physician regularly while taking this medicine, especially in the first few months of treatment.
The physician will check to make sure the medicine is
2466

working as it should and will note unwanted side
effects. The physician may also need to adjust the
dosage during this period.
Several weeks may be needed for the effects of this
medicine to be felt. Be sure to keep taking it as directed, even if it does not seem to be helping.
Do not stop taking this medicine suddenly.
Tapering the dose may be necessary to reduce the
chance of withdrawal symptoms. If it is necessary to
stop taking the drug, check with the physician who
prescribed it for instructions on how to stop.
MAO inhibitors may be taken with or without
food, on a full or empty stomach. Check package
directions or ask the physician or pharmacist for
instructions on how to take the medicine. Remember
that some foods and beverages must be avoided during
treatment with MAO inhibitors.

Precautions
The effects of this medicine may continue for
2 weeks or more after patients stop taking it. All precautions should be observed during this period, as well
as throughout treatment with MAO inhibitors.
MAO inhibitors may cause serious and possibly
life-threatening reactions, such as sudden high blood
pressure, when taken with certain foods, beverages, or
medicines. The dangerous reactions may not begin
until several hours after consuming these things.
Aged cheeses, red wines, smoked or pickled meats,
chocolate, caffeinated beverages, and foods containing monosodium glutamate (MSG) are among the
foods and drinks to be avoided. Be sure to get a
complete list from the physician who prescribed the
medicine or the pharmacist who filled the prescription.
Do not drink any alcoholic beverages or reducedalcohol or alcohol-free beer or wine while taking this
medicine.
Anyone who is taking MAO inhibitors should not
use any other medicine unless it has been approved or
prescribed by a physician who knows that they are
taking MAO inhibitors. This includes nonprescription
(over-the-counter) medicines such as sleep aids; medicines for colds, cough, hay fever, or asthma (including
nose drops or sprays); medicines to increase alertness
or keep from falling asleep; and appetite control
products.
Because MAO inhibitors work on the central nervous system, they may add to the effects of alcohol
and other drugs that slow down the central nervous
system, such as antihistamines, cold medicine, allergy
GALE ENCYCLOPEDIA OF MEDICINE

MAO inhibitors may interact with medicines used
during surgery, dental procedures, or emergency treatment. These interactions could increase the chance of
side effects. Anyone who is taking MAO inhibitors
should be sure to tell the health care professional in
charge before having any surgical or dental procedures or receiving emergency treatment.

ANGINA. MAO inhibitors may make people feel
unusually energetic and healthy. People with angina
(chest pain) should be careful not to overexert themselves and should check with their physicians before
increasing their levels of activity or exercise.
OTHER MEDICAL CONDITIONS. Before using MAO
inhibitors, people with any of these medical problems
should make sure their physicians are aware of their
conditions:


Alcohol abuse



High blood pressure



Recent heart attack or stroke



Heart or blood vessel disease



Liver disease



Kidney disease

These medicines also make some people feel lightheaded, dizzy, or faint when they get up after sitting or
lying down. To lessen the problem, get up gradually
and hold onto something for support if possible.



Frequent or severe headaches



Epilepsy



Parkinson’s disease

Older people may be especially sensitive to the
effects of MAO inhibitors. This may increase the chance
of side effects, such as dizziness or lightheadedness.



Current or past mental illness



Asthma or bronchitis



Overactive thyroid



Pheochromocytoma (a tumor of the adrenal gland).

Some people feel drowsy, dizzy, lightheaded, or
less alert when using MAO inhibitors. The drugs may
also cause blurred vision. For these reasons, anyone
who takes these drugs should not drive, use machines
or do anything else that might be dangerous until they
have found out how the drugs affect them.

Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take MAO inhibitors. Before taking these drugs,
be sure to let the physician know about any of these
conditions:

USE OF CERTAIN MEDICINES. Taking MAO inhibitors with certain other drugs may affect the way the
drugs work or may increase the chance of side effects.

ALLERGIES. Anyone who has had unusual reac-

The most common side effects are dizziness, lightheadedness, drowsiness, tiredness, weakness, blurred
vision, shakiness or trembling, restlessness, sleep problems or twitching during sleep, increased appetite
(especially for sweets), weight gain, decreased sexual
ability, decreased amount of urine, and mild headache.
These problems usually go away as the body adjusts to
the drug and do not require medical treatment unless
they interfere with normal activities.

tions to MAO inhibitors in the past should let his or
her physician know before taking the drugs again. The
physician should also be told about any allergies to
foods, dyes, preservatives, or other substances.
PREGNANCY. Studies suggest that taking MAO
inhibitors during pregnancy may increase the risk of
birth defects or problems in the newborn after birth.
Women who are pregnant or who may become pregnant should check with their physicians before using
MAO inhibitors.
BREASTFEEDING. MAO inhibitors may pass into
breast milk, but no problems have been reported in
nursing babies whose mothers took the medicine.
Women who are breastfeeding their babies should
check with their physicians before using this medicine.
DIABETES. MAO inhibitors may affect blood
sugar levels. Persons with diabetes who are taking
this medicine and notice changes in their blood or
urine tests should check with their physicians.

GALE ENCYCLOPEDIA OF MEDICINE

Side effects

More serious side effects may occur. If any of the
following side effects occur, stop taking the medicine
and get emergency medical attention immediately:


Severe chest pain



Severe headache



Stiff, sore neck



Enlarged pupils



Increased sensitivity of eyes to light



Fast or slow heartbeat
2467

Monoamine oxidase inhibitors

medicine, sleep aids, medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants.
Anyone taking MAO inhibitors should check with
his or her physician before taking any of the above.

Mood disorders

KEY TERMS
Anxiety—Worry or tension in response to real or
imagined stress, danger, or dreaded situations.
Physical reactions, such as fast pulse, sweating, trembling, fatigue, and weakness may accompany anxiety.
Central nervous system—The brain and spinal
cord.
Depression—A mental condition in which people
feel extremely sad and lose interest in life. People
with depression may also have sleep problems and
loss of appetite and may have trouble concentrating and carrying out everyday activities.
Neurotransmitter—A chemical that carries messages from one nerve cell to another.
Phobia—An intense, abnormal, or illogical fear of
something specific, such as heights or open spaces.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug to which he or she has
become dependent.



Sweating, with or without fever or cold, clammy skin



Nausea and vomiting.

Other side effects may occur. Anyone who has
unusual or troublesome symptoms after taking MAO
inhibitors should get in touch with his or her physician.

Interactions
MAO inhibitors may interact with many other
medicines. When this happens, the effects of one or
both of the drugs may change or the risk of side effects
may be greater. Anyone who takes MAO inhibitors
must check with his or her physician before taking any
other prescription or nonprescription (over-the-counter) medicine. Among the drugs that may interact
with MAO inhibitors are:


Central nervous system (CNS) depressants such as
medicine for allergies, colds, hay fever, and asthma;
sedatives; tranquilizers; prescription pain medicine;
muscle relaxants; medicine for seizures; sleep aids;
barbiturates; and anesthetics



Medicine for high blood pressure



Other antidepressants, including tricyclic antidepressants (such as Tofranil and Norpramin), antidepressants that raise serotonin levels (such as
Prozac and Zoloft), and bupropion (Wellbutrin)

2468



Diabetes medicines taken by mouth



Insulin



Water pills (diuretics).

The list above does not include every drug that
may interact with MAO inhibitors. Check with a physician or pharmacist before combining MAO inhibitors with any other prescription or nonprescription
(over-the-counter) medicine.
Nancy Ross-Flanigan

Mononucleosis see Infectious
mononucleosis
Montezuma’s revenge see Traveler’s
diarrhea

Mood disorders
Definition
Mood disorders are mental disorders characterized by periods of depression, sometimes alternating
with periods of elevated mood.

Description
While many people go through sad or elated
moods from time to time, people with mood disorders
suffer from severe or prolonged mood states that disrupt their daily functioning. Among the general mood
disorders classified in the fourth edition (1994) of the
Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV) are major depressive disorder, bipolar
disorder, and dysthymia.
In classifying and diagnosing mood disorders,
doctors determine if the mood disorder is unipolar or
bipolar. When only one extreme in mood (the
depressed state) is experienced, this type of depression
is called unipolar. Major depression refers to a single
severe period of depression, marked by negative or
hopeless thoughts and physical symptoms like fatigue.
In major depressive disorder, some patients have isolated episodes of depression. In between these episodes, the patient does not feel depressed or have
other symptoms associated with depression. Other
patients have more frequent episodes.
Bipolar depression or bipolar disorder (sometimes
called manic depression) refers to a condition in which
people experience two extremes in mood. They
GALE ENCYCLOPEDIA OF MEDICINE

Dysthymia is a recurrent or lengthy depression
that may last a lifetime. It is similar to major depressive disorder, but dysthymia is chronic, long-lasting,
persistent, and mild. Patients may have symptoms that
are not as severe as major depression, but the symptoms last for many years. It seems that a mild form of
the depression is always present. In some cases, people
also may experience a major depressive episode on top
of their dysthymia, a condition sometimes referred to
as a ‘‘double depression.’’

Causes and symptoms
Mood disorders tend to run in families. These
disorders are associated with imbalances in certain
chemicals that carry signals between brain cells (neurotransmitters). These chemicals include serotonin,
norepinephrine, and dopamine. Women are more vulnerable to unipolar depression than are men. Major
life stressors (like divorce, serious financial problems,
death of a family member, etc.) will often provoke the
symptoms of depression in susceptible people.
Major depression is more serious than just feeling
‘‘sad’’ or ‘‘blue.’’ The symptoms of major depression
may include:

increase in energy, others who know the person well
see a marked difference in behavior. The patient may
seem to be in a frenzy and often will make poor, bizarre,
or dangerous choices in his/her personal and professional lives. Hypomania is not as severe as mania and
does not cause the level of impairment in work and
social activities that mania can.

Diagnosis
Doctors diagnose mood disorders based on the
patient’s description of the symptoms as well as the
patient’s family history. The length of time the patient
has had symptoms also is important. Generally
patients are diagnosed with dysthymia if they feel
depressed more days than not for at least two years.
The depression is mild but long lasting. In major
depressive disorder, the patient is depressed almost
all day nearly every day of the week for at least two
weeks. The depression is severe. Sometimes laboratory
tests are performed to rule out other causes for the
symptoms (like thyroid disease). The diagnosis may be
confirmed when a patient responds well to medication.

Treatment
The most effective treatment for mood disorders
is a combination of medication and psychotherapy. In
fact, a 2003 report revealed that people on medication
for bipolar disorder had better results if they also
participated in family-focused therapy. The four different classes of drugs used in mood disorders are:



Loss of appetite





A change in sleep patterns, like not sleeping (insomnia) or sleeping too much

Heterocyclic antidepressants (HCAs), like amitriptyline (Elavil)



Selective serotonin reuptake inhibitors (SSRI inhibitors), like fluoxetine (Prozac), paroxetine (Paxil),
and sertraline (Zoloft)



Monoamine oxidase inhibitors (MAOI inhibitors),
like phenelzine sulfate (Nardil) and tranylcypromine
sulfate (Parnate)



Mood stabilizers, like lithium carbonate (Eskalith)
and valproate, often used in people with bipolar
mood disorders.



Feelings of worthlessness, hopelessness, or inappropriate guilt



Fatigue



Difficulty in concentrating or making decisions



Overwhelming and intense feelings of sadness or
grief



Disturbed thinking. The person may also have physical symptoms like stomachaches or headaches.

Bipolar disorder includes mania or hypomania.
Mania is an abnormal elevation in mood. The person
may be excessively cheerful, have grandiose ideas, and
may sleep less. He or she may talk nonstop for hours,
have unending enthusiasm, and demonstrate poor
judgement. Sometimes the elevation in mood is marked
by irritability and hostility rather than cheerfulness.
While the person may at first seem normal with an
GALE ENCYCLOPEDIA OF MEDICINE

A number of psychotherapy approaches are useful as well. Interpersonal psychotherapy helps the
patient recognize the interaction between the mood
disorder and interpersonal relationships. Cognitivebehavioral therapy explores how the patient’s view of
the world may be affecting his or her mood and
outlook.
When depression fails to respond to treatment or
when there is a high risk of suicide, electroconvulsive
2469

Mood disorders

alternate between depression (the ‘‘low’’ mood) and
mania or hypomania (the ‘‘high’’ mood). These
patients go from depression to a frenzied, abnormal
elevation in mood. Mania and hypomania are similar,
but mania is usually more severe and debilitating to
the patient.

Motion sickness

therapy (ECT) sometimes is used. ECT is believed to
affect neurotransmitters like the medications do.
Patients are anesthetized and given muscle relaxants
to minimize discomfort. Then low-level electric current is passed through the brain to cause a brief convulsion. The most common side effect of ECT is mild,
short-term memory loss.

Alternative treatment
There are many alternative therapies that may
help in the treatment of mood disorders, including
acupuncture, botanical medicine, homeopathy, aromatherapy, constitutional hydrotherapy, and light
therapy. The therapy used is an individual choice.
Short-term clinical studies have shown that the herb
St. John’s wort (Hypericum perforatum) can effectively treat some types of depression. Though it
appears very safe, the herb may have some side effects
and its long-term effectiveness has not been proven.
It has not been tested in patients with bipolar disorder. Despite uncertainty concerning its effectiveness,
a 2003 report said acceptance of the treatment continues to increase. A poll showed that about 41% of
15,000 science professionals in 62 countries said they
would use St. John’s wort for mild to moderate
depression. Although St. John’s wort appears to be
a safe alternative to conventional antidepressants,
care should be taken, as the herb can interfere with
the actions of some pharmaceuticals. The usual dose
is 300 mg three times daily. St. John’s wort and antidepressant drugs should not be taken simultaneously,
so patients should tell their doctor if they are taking
St. John’s wort.

Prognosis

KEY TERMS
Cognitive therapy—Psychotherapy technique
designed to help people change their attitudes,
perceptions, and patterns of thinking.
Electroconvulsive therapy (ECT)—Therapy for
mood disorders that involves passing electrical current through the brain in order to create a brief
convulsion.
Neurotransmitter—A chemical that aids or alters
the transmission of impulses between the points
that connect nerves.
Serotonin—A chemical messenger in the brain
thought to play a role in mood regulation.

ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
National Depressive and Manic Depressive Association
(NDMDA). 730 N. Franklin St., Ste. 501,
Chicago, IL 60610. (800) 826-3632. <http://
www.ndmda.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Robert Scott Dinsmoor
Teresa G. Odle

Morning after pill see Mifepristone

Most cases of mood disorders can be successfully
managed if properly diagnosed and treated.

Prevention
People can take steps to improve mild depression
and keep it from becoming worse. They can learn
stress management (like relaxation training or breathing exercises), exercise regularly, and avoid drugs or
alcohol.
Resources
PERIODICALS

‘‘Family-focused Therapy May Reduce Relapse Rate.’’
Health & Medicine Week September 29, 2003: 70.
‘‘St. John’s Wort Healing Reputation Upheld.’’
Nutraceuticals International. September 2003.
2470

Motion sickness
Definition
Motion sickness is the uncomfortable dizziness,
nausea, and vomiting that people experience when
their sense of balance and equilibrium is disturbed by
constant motion. Riding in a car, aboard a ship or
boat, or riding on a swing all cause stimulation of the
vestibular system and visual stimulation that often
leads to discomfort. While motion sickness can be
bothersome, it is not a serious illness, and can be
prevented.
GALE ENCYCLOPEDIA OF MEDICINE

Patricia Suzanne Cowings was born on December
15, 1948, in New York City. She was one of four children
born to Sadie and Albert Cowings, a grocery store owner.
Cowings showed interest in science by the time she was
eleven years old. She enrolled in the State University of
New York at Stony Brook, earning her bachelor’s degree
with honors in 1970. She began her graduate work at the
University of California at Davis where she was awarded
both her master’s and her doctoral degrees in 1973.
Cowings also received an associateship from the
National Research Council that same year, which
allowed her to complete two years of research at
NASA’s Ames Research Center. She has held a position
as a researcher with Ames since 1977.
Cowings’s work at Ames’ Psychophysiological
Research Laboratory led to major breakthroughs for
astronauts. Her pioneering experiments with biofeedback as a method to control bodily functions has
proven very effective for astronaut crews who experience
‘‘zero-gravity sickness syndrome.’’ Her program was
finally used during the 1992 Endeavour space flight.
Presently, Cowings is researching exercises that will
allow astronauts to maintain muscle strength while in
zero gravity. She has published numerous papers with
her colleague and husband, William B. Toscano. In addition, she has written articles including The Relationship
of Motion Sickness Susceptibility to Learned Autonomic
Control for Symptom Suppression (1982), AutogenicFeedback Training as a Preventive Method for Space
Adaptation Syndrome (1985), and Autogenic-Feedback
Training: A Preventive Method for Motion and Space
Sickness (1990).

Description
Motion sickness is a common problem, with
nearly 80% of the general population suffering from
it at one time in their lives. People with migraine headaches or Ménière’s syndrome, however, are more
likely than others to have recurrent episodes of motion
sickness. Researchers at the Naval Medical Center in
San Diego, California, reported in 2003 that 70% of
research subjects with severe motion sickness had
abnormalities of the vestibular system; these abnormalities are often found in patients diagnosed with
migraines or Ménière’s disease.
While motion sickness may occur at any age, it is
more common in children over the age of two, with the
majority outgrowing this susceptibility.
GALE ENCYCLOPEDIA OF MEDICINE

When looking at why motion sickness occurs, it is
helpful to understand the role of the sensory organs.
The sensory organs control a body’s sense of balance
by telling the brain what direction the body is pointing, the direction it is moving, and if it is standing still
or turning. These messages are relayed by the inner
ears (or labyrinth); the eyes; the skin pressure receptors, such as in those in the feet; the muscle and joint
sensory receptors, which track what body parts are
moving; and the central nervous system (the brain
and spinal cord), which is responsible for processing
all incoming sensory information.
Motion sickness and its symptoms surface when
conflicting messages are sent to the central nervous
system. An example of this is reading a book in the
back seat of a moving car. The inner ears and skin
receptors sense the motion, but the eyes register only
the stationary pages of the book. This conflicting
information may cause the usual motion sickness
symptoms of dizziness, nausea and vomiting.

Causes and symptoms
While all five of the body’s sensory organs contribute to motion sickness, excess stimulation to the
vestibular system within the inner ear (the body’s
‘‘balance center’’) has been shown to be one of the
primary reasons for this condition. Balance problems,
or vertigo, are caused by a conflict between what is
seen and how the inner ear perceives it, leading to
confusion in the brain. This confusion may result in
higher heart rates, rapid breathing, nausea and sweating, along with dizziness and vomiting.
Pure optokinetic motion sickness is caused solely
by visual stimuli, or what is seen. The optokinetic
system is the reflex that allow the eyes to move when
an object moves. Many people suffer when what they
view is rotating or swaying, even if they are standing
still.
Additional factors that may contribute to the
occurrence of motion sickness include:


Poor ventilation.



Anxiety or fear. Both have been found to lower a
person’s threshold for experiencing motion sickness
symptoms.



Food. It is recommended that a heavy meal of spicy
and greasy foods be avoided before and during a trip.



Alcohol. A drink is often thought to help calm the
nerves, but in this case it could upset the stomach
further. A hangover for the next morning’s trip may
also lead to motion sickness.
2471

Motion sickness

PATRICIA SUZANNE COWINGS
(1948– )

Motion sickness





Genetic factors. Research suggests that some people
inherit a predisposition to motion sickness. This predisposition is more marked in some ethnic groups
than in others; one study published in 2002 found
that persons of Chinese or Japanese ancestry are
significantly more vulnerable to motion sickness
than persons of British ancestry.



Benadryl (and others). Includes the active ingredient
diphenhydramine and is not for use in children under
age 6.



Dramamine (and others). Includes the active ingredient dimenhydrinate and is not for use in children
under age 2.

Pregnancy. Susceptibility in women to vomiting during pregnancy appears to be related to motion sickness, although the precise connections are not well
understood as of 2004.



Bonine (and others). Includes the active ingredient
meclizine and is not for use in children under
age 12.

Often viewed as a minor annoyance, some travelers
are temporarily immobilized by motion sickness, and a
few continue to feel its effects for hours and even days
after a trip (the ‘‘mal d’embarquement’’ syndrome).

Diagnosis
Most cases of motion sickness are mild and selftreatable disorders. If symptoms such as dizziness
become chronic, a doctor may be able to help alleviate
the discomfort by looking further into a patient’s general health. Questions regarding medications, head
injuries, recent infections, and other questions about
the ear and neurological system will be asked. An
examination of the ears, nose, and throat, as well as
tests of nerve and balance function, may also be
completed.
Severe cases of motion sickness symptoms, and
those that become progressively worse, may require
additional, specific tests. Diagnosis in these situations
deserves the attention and care of a doctor with specialized skills in diseases of the ear, nose, throat, equilibrium, and neurological system.

Treatment
There are a variety of medications to help ease the
symptoms of motion sickness, and most of these are
available without a prescription. Known as over-thecounter (OTC) medications, it is recommended that
these be taken 30-60 minutes before traveling to prevent motion sickness symptoms, as well as during an
extended trip.
Drugs
The following OTC drugs consist of ingredients
that have been considered safe and effective for the
treatment of motion sickness by the Food and Drug
Administration:


Marezine (and others). Includes the active ingredient
cyclizine and is not for use in children under age 6.

2472

Each of the active ingredients listed above are
antihistamines whose main side effect is drowsiness.
Caution should be used when driving a vehicle
or operating machinery, and alcohol should be
avoided when taking any drug for motion sickness.
Large doses of OTC drugs for motion sickness
may also cause dry mouth and occasional blurred
vision.
The side effects of cinnarizine and the other antihistamine antiemetics indicate that they should not be
used by members of flight crews responsible for the
control of aircraft or for other tasks that require sustained attention and alertness.
The Food and Drug Administration (FDA)
recommends that people with emphysema, chronic
bronchitis, glaucoma, or difficulty urinating due to an
enlarged prostate do not use OTC drugs for motion
sickness unless directed by their doctor.
Longer trips may require a prescription medication called scopolamine (Transderm Scop). Formerly
used in the transdermal skin patch (now discontinued), travelers must now ask their doctor to prescribe
it in the form of a gel. In gel form, scopolamine is most
effective when smeared on the arm or neck and covered with a bandage.
Another prescription drug that is sometimes given
for motion sickness is ondansetron (Zofran), which
was originally developed to treat nausea associated
with cancer chemotherapy. Unlike cyclizine, ondansetron appears to be safe for use in children under the
age of six.
Several newer antiemetic medications are under
development as of early 2004. The most promising of
these newer drugs is a class of compounds known as
neurokinin-1 (substance P) antagonists. The neurokinins are being tested for the control of nausea following cancer chemotherapy as well as nausea related
to motion sickness. In March 2003 the FDA
approved the first of this new class of antiemetic
drugs. Known as aprepitant, it is sold under the
trade name Emend.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Alternative treatments for motion sickness have
become widely accepted as a standard means of care.
Ginger (Zingiber officinale) in its various forms is
often used to calm the stomach, and it is now known
that the oils it contains (gingerols and shogaols)
appear to relax the intestinal tract in addition to mildly
depressing the central nervous system. Some of the
most effective forms of ginger include the powdered,
encapsulated form; ginger tea prepared from sliced
ginger root; or candied pieces. All forms of ginger
should be taken on an empty stomach.

Acupressure—Often described as acupuncture
without needles, acupressure is a traditional
Chinese medical technique based on theory of qi
(life energy) flowing in energy meridians or channels in the body. Applying pressure with the thumb
and fingers to acupressure points can relieve specific conditions and promote overall balance and
health.

Placing manual pressure on the Neiguan or
Pericardium-6 acupuncture point (located about three
finger-widths above the wrist on the inner arm), either
by acupuncture, acupressure, or a mild, electrical
pulse, has shown to be effective against the symptoms
of motion sickness. Elastic wristbands sold at most
drugstores are also used as a source of relief due to
the pressure it places in this area. Pressing the small
intestine 17 (just below the earlobes in the indentations
behind the jawbone) may also help in the functioning
of the ear’s balancing mechanism.

Neurological system—The tissue that initiates and
transmits nerve impulses including the brain, spinal
cord, and nerves.
Optokinetic —A reflex that causes a person’s eyes
to move when their field of vision moves.

Acupuncture—Based on the same traditional
Chinese medical foundation as acupressure, acupuncture uses sterile needles inserted at specific
points to treat certain conditions or relieve pain.

Vertigo—The sensation of moving around in space,
or objects moving around a person. It is a disturbance of equilibrium.
Vestibular system—The brain and parts of the inner
ear that work together to detect movement and
position.

There are several homeopathic remedies that
work specifically for motion sickness. They include
Cocculus, Petroleum, and Tabacum.

Prognosis
While there is no cure for motion sickness, its
symptoms can be controlled or even prevented. Most
people respond successfully to the variety of treatments, or avoid the unpleasant symptoms through
prevention methods.



Eat a light meal before traveling, or if already nauseated, avoid food altogether.



Avoid watching or talking to another traveler who is
having motion sickness.



Take motion sickness medicine at least 30-60 minutes
before travel begins, or as recommended by a
physician.



Learn to live with the condition. Even those who
frequently endure motion sickness can learn to travel
by anticipating the conditions of their next trip.
Research also suggests that increased exposure to
the stimulation that causes motion sickness may
help decrease its symptoms on future trips.

Prevention
Because motion sickness is easier to prevent than
treat once it has begun, the best treatment is prevention. The following steps may help deter the unpleasant symptoms of motion sickness before they occur:


Avoid reading while traveling, and do not sit in a
backward facing seat.



Always ride where the eyes may see the same motion
that the body and inner ears feel. Safe positions
include the front seat of the car while looking at
distant scenery; the deck of a ship where the horizon
can be seen; and sitting by the window of an airplane.
The least motion on an airplane is in a seat over the
wings.



Maintain a fairly straight-ahead view.

GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Pelletier, Dr. Kenneth R. The Best Alternative Medicine.
New York: Simon and Schuster, 2002.
PERIODICALS

Black, F. O. ‘‘Maternal Susceptibility to Nausea and
Vomiting of Pregnancy: Is the Vestibular System

2473

Motion sickness

Alternative treatment

Movement disorders

Involved?’’ American Journal of Obstetrics and
Gynecology 185, Supplement 5 (May 2002): S204-S209.
Bos, J. E., W. Bles, and B. de Graaf. ‘‘Eye Movements to Yaw,
Pitch, and Roll About Vertical and Horizontal Axes:
Adaptation and Motion Sickness.’’ Aviation, Space, and
Environmental Medicine 73 (May 2002): 434-444.
Hamid, Mohamed, MD, PhD, and Nicholas Lorenzo, MD.
‘‘Dizziness, Vertigo, and Imbalance.’’ eMedicine
September 17, 2002. <http://emedicine.com/neuro/
topic693.htm>.
Harm, D. L., and T. T. Schlegel. ‘‘Predicting Motion
Sickness During Parabolic Flight.’’ Autonomic
Neuroscience 31 (May 2002): 116-121.
Hoffer, M. E., K. Gottshall, R. D. Kopke, et al. ‘‘Vestibular
Testing Abnormalities in Individuals with Motion
Sickness.’’ Otology and Neurotology 24 (July 2003):
633–636.
Keim, Samuel, MD, and Michael Kent, MD. ‘‘Vomiting and
Nausea.’’ eMedicine April 29, 2002. <http://emedicine.com/aaem/topic476.htm>.
Liu, L., L. Yuan, H. B. Wang, et al. ‘‘The Human
Alpha(2A)-AR Gene and the Genotype of Site -1296
and the Susceptibility to Motion Sickness.’’ [in Chinese]
Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao
(Shanghai) 34 (May 2002): 291-297.
Loewen, P. S. ‘‘Anti-Emetics in Development.’’ Expert
Opinion on Investigational Drugs 11 (June 2002): 801-805.
Nicholson, A. N., et al. ‘‘Central Effects of Cinnarizine:
Restricted Use in Aircrew’’ Aviation, Space, and
Environmental Medicine 73 (June 2002): 570-574.
O’Brien, C. M., G. Titley, and P. Whitehurst. ‘‘A
Comparison of Cyclizine, Ondansetron and Placebo as
Prophylaxis Against Postoperative Nausea and
Vomiting in Children.’’ Anaesthesia 58 (July 2003):
707–711.
Patel, L., and C. Lindley. ‘‘Aprepitant—A Novel NK1Receptor Antagonist.’’ Expert Opinion in
Pharmacotherapy 4 (December 2003): 2279–2296.

Movement disorders
Definition
Movement disorders are a group of diseases and
syndromes affecting the ability to produce and control
movement.

Description
Though it seems simple and effortless, normal
movement in fact requires an astonishingly complex
system of control. Disruption of any portion of this
system can cause a person to produce movements that
are too weak, too forceful, too uncoordinated, or too
poorly controlled for the task at hand. Unwanted
movements may occur at rest. Intentional movement
may become impossible. Such conditions are called
movement disorders.
Abnormal movements themselves are symptoms
of underlying disorders. In some cases, the abnormal
movements are the only symptoms. Disorders causing
abnormal movements include:


Parkinson’s disease



Parkinsonism caused by drugs or poisons



Parkinson-plus syndromes (progressive supranuclear
palsy, multiple system atrophy, and cortical-basal
ganglionic degeneration)



Huntington’s disease



Wilson’s disease



Inherited ataxias (Friedreich’s ataxia, MachadoJoseph disease, and spinocerebellar ataxias)



Tourette syndrome and other tic disorders

ORGANIZATIONS



Essential tremor

Civil Aerospace Medical Institute. P. O. Box 20582,
Oklahoma City, OK 73125. (202) 366-4000.
<http://www.cami.jccbi.gov>.
National Aeronautics and Space Administration. Office of
Biological and Physical Research.
<http://www.spaceresearch.nasa.gov>.
Vestibular Disorders Association. P.O. Box 4467, Portland,
OR 97208-4467. (800) 837-8428. <http://www.teleport.com/~veda>.



Restless leg syndrome



Dystonia



Stroke



Cerebral palsy



Encephalopathies



Intoxication



Poisoning by carbon monoxide, cyanide, methanol,
or manganese.

Beth A. Kapes
Rebecca J. Frey, PhD

Mountain sickness see Altitude sickness
Mouth cancer see Head and neck cancer
2474

Causes and symptoms
Causes
Movement is produced and coordinated by several interacting brain centers, including the motor
GALE ENCYCLOPEDIA OF MEDICINE

To understand how movement disorders occur, it
is helpful to consider a normal voluntary movement,
such as reaching to touch a nearby object with the
right index finger. To accomplish the desired movement, the arm must be lifted and extended. The hand
must be held out to align with the forearm, and the
forefinger must be extended while the other fingers
remain flexed.
THE MOTOR CORTEX. Voluntary motor commands
begin in the motor cortex located on the outer,
wrinkled surface of the brain. Movement of the right
arm is begun by the left motor cortex, which generates
a large volley of signals to the involved muscles. These
electrical signals pass along upper motor neurons
through the midbrain to the spinal cord. Within the
spinal cord, they connect to lower motor neurons,
which convey the signals out of the spinal cord to the
surface of the muscles involved. Electrical stimulation
of the muscles causes contraction, and the force of
contraction pulling on the skeleton causes movement
of the arm, hand, and fingers.

Damage to or death of any of the neurons along
this path causes weakness or paralysis of the affected
muscles.
ANTAGONISTIC MUSCLE PAIRS. This picture of
movement is too simple, however. One important
refinement to it comes from considering the role of
opposing, or antagonistic, muscle pairs. Contraction
of the biceps muscle, located on the top of the upper
arm, pulls on the forearm to flex the elbow and bend
the arm. Contraction of the triceps, located on the
opposite side, extends the elbow and straightens the
arm. Within the spine, these muscles are normally
wired so that willed (voluntary) contraction of one is
automatically accompanied by blocking of the other.
In other words, the command to contract the biceps
provokes another command within the spine to prevent contraction of the triceps. In this way, these
antagonist muscles are kept from resisting one
another. Spinal cord or brain injury can damage this
control system and cause involuntary simultaneous
contraction and spasticity, an increase in resistance
to movement during motion.
THE CEREBELLUM. Once the movement of the arm
is initiated, sensory information is needed to guide the
finger to its precise destination. In addition to sight,

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the most important source of information comes from
the ‘‘position sense’’ provided by the many sensory
neurons located within the limbs (proprioception).
Proprioception is what allows you to touch your
nose with your finger even with your eyes closed. The
balance organs in the ears provide important information about posture. Both postural and proprioceptive
information are processed by a structure at the rear of
the brain called the cerebellum. The cerebellum sends
out electrical signals to modify movements as they
progress, ‘‘sculpting’’ the barrage of voluntary commands into a tightly controlled, constantly evolving
pattern. Cerebellar disorders cause inability to control
the force, fine positioning, and speed of movements
(ataxia). Disorders of the cerebellum may also impair
the ability to judge distance so that a person under- or
over-reaches the target (dysmetria). Tremor during
voluntary movements can also result from cerebellar
damage.
THE BASAL GANGLIA. Both the cerebellum and the
motor cortex send information to a set of structures
deep within the brain that help control involuntary
components of movement (basal ganglia). The basal
ganglia send output messages to the motor cortex,
helping to initiate movements, regulate repetitive or
patterned movements, and control muscle tone.

Circuits within the basal ganglia are complex.
Within this structure, some groups of cells begin the
action of other basal ganglia components and some
groups of cells block the action. These complicated
feedback circuits are not entirely understood. Disruptions of these circuits are known to cause several
distinct movement disorders. A portion of the basal
ganglia called the substantia nigra sends electrical signals that block output from another structure called the
subthalamic nucleus. The subthalamic nucleus sends
signals to the globus pallidus, which in turn blocks the
thalamic nuclei. Finally, the thalamic nuclei send signals to the motor cortex. The substantia nigra, then,
begins movement and the globus pallidus blocks it.
This complicated circuit can be disrupted at several points. For instance, loss of substantia nigra cells,
as in Parkinson’s disease, increases blocking of the
thalamic nuclei, preventing them from sending signals
to the motor cortex. The result is a loss of movement
(motor activity), a characteristic of Parkinson’s.
In contrast, cell loss in early Huntington’s disease
decreases blocking of signals from the thalamic nuclei,
causing more cortex stimulation and stronger but
uncontrolled movements.
Disruptions in other portions of the basal ganglia
are thought to cause tics, tremors, dystonia, and a
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Movement disorders

cortex, the cerebellum, and a group of structures in
the inner portions of the brain called the basal ganglia. Sensory information provides critical input on
the current position and velocity of body parts, and
spinal nerve cells (neurons) help prevent opposing
muscle groups from contracting at the same time.

Movement disorders

variety of other movement disorders, although the
exact mechanisms are not well understood.
Some movement disorders, including Huntington’s
disease and inherited ataxias, are caused by inherited
genetic defects. Some disease that cause sustained muscle contraction limited to a particular muscle group
(focal dystonia) are inherited, but others are caused by
trauma. The cause of most cases of Parkinson’s disease
is unknown, although genes have been found for some
familial forms.
Symptoms
Abnormal movements are broadly classified as
either hyperkinetic–too much movement–and hypokinetic–too little movement. Hyperkinetic movements
include:


Dystonia. Sustained muscle contractions, often causing twisting or repetitive movements and abnormal
postures. Dystonia may be limited to one area (focal)
or may affect the whole body (general). Focal dystonias may affect the neck (cervical dystonia or torticollis), the face (one-sided or hemifacial spasm,
contraction of the eyelid or blepharospasm, contraction of the mouth and jaw or oromandibular dystonia, simultaneous spasm of the chin and eyelid or
Meige syndrome), the vocal cords (laryngeal dystonia), or the arms and legs (writer’s cramp, occupational cramps). Dystonia may be painful as well as
incapacitating.



Tremor. Uncontrollable (involuntary) shaking of a
body part. Tremor may occur only when muscles are
relaxed or it may occur only during an action or
holding an active posture.



Tics. Involuntary, rapid, nonrhythmic movement or
sound. Tics can be controlled briefly.



Myoclonus. A sudden, shock-like muscle contraction. Myoclonic jerks may occur singly or repetitively. Unlike tics, myoclonus cannot be controlled
even briefly.



Chorea. Rapid, nonrhythmic, usually jerky movements, most often in the arms and legs.



Ballism. Like chorea, but the movements are much
larger, more explosive and involve more of the arm
or leg. This condition, also called ballismus, can
occur on both sides of the body or on one side only
(hemiballismus).



Akathisia. Restlessness and a desire to move to
relieve uncomfortable sensations. Sensations may
include a feeling of crawling, itching, stretching, or
creeping, usually in the legs.

2476



Athetosis. Slow, writhing, continuous, uncontrollable movement of the arms and legs.
Hypokinetic movements include:



Bradykinesia. Slowness of movement.



Freezing. Inability to begin a movement or involuntary stopping of a movement before it is completed.



Rigidity. An increase in muscle tension when an arm
or leg is moved by an outside force.



Postural instability. Loss of ability to maintain
upright posture caused by slow or absent righting
reflexes.

Diagnosis
Diagnosis of movement disorders requires a careful medical history and a thorough physical and neurological examination. Brain imaging studies are
usually performed. Imaging techniques include computed tomography scan (CT scan), positron emission
tomography (PET), or magnetic resonance imaging
(MRI) scans. Routine blood and urine analyses are
performed. A lumbar puncture (spinal tap) may be
necessary. Video recording of the abnormal movement is often used to analyze movement patterns and
to track progress of the disorder and its treatment.
Genetic testing is available for some forms of movement disorders.

Treatment
Treatment of a movement disorder begins with
determining its cause. Physical and occupational therapy may help make up for lost control and strength.
Drug therapy can help compensate for some imbalances of the basal ganglionic circuit. For instance,
levodopa (L-dopa) or related compounds can substitute for lost dopamine-producing cells in Parkinson’s
disease. Conversely, blocking normal dopamine
action is a possible treatment in some hyperkinetic
disorders, including tics. Oral medications can also
help reduce overall muscle tone. Local injections of
botulinum toxin can selectively weaken overactive
muscles in dystonia and spasticity. Destruction of peripheral nerves through injection of phenol can reduce
spasticity. All of these treatments may have some side
effects.
Surgical destruction or inactivation of basal ganglionic circuits has proven effective for Parkinson’s
disease and is being tested for other movement disorders. Transplantation of fetal cells into the basal ganglia has produced mixed results in Parkinson’s disease.

GALE ENCYCLOPEDIA OF MEDICINE

Botulinum toxin—Any of a group of potent bacterial
toxins or poisons produced by different strains of the
bacterium Clostridium botulinum. The toxins cause
muscle paralysis, and thus force the relaxation of a
muscle in spasm.

Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.

Cerebral palsy—A movement disorder caused by a
permanent brain defect or injury present at birth or
shortly after. It is frequently associated with premature birth. Cerebral palsy is not progressive.
Computed tomography (CT)—An imaging technique in which cross-sectional x rays of the body are
compiled to create a three-dimensional image of the
body’s internal structures.
Encephalopathy—An abnormality in the structure or
function of tissues of the brain.

Parkinson’s disease—A slowly progressive disease
that destroys nerve cells in the basal ganglia and
thus causes loss of dopamine, a chemical that aids
in transmission of nerve signals (neurotransmitter).
Parkinson’s is characterized by shaking in resting
muscles, a stooping posture, slurred speech, muscular stiffness, and weakness.

Essential tremor—An uncontrollable (involuntary)
shaking of the hands, head, and face. Also called
familial tremor because it is sometimes inherited, it
can begin in the teens or in middle age. The exact
cause is not known.
Fetal tissue transplantation—A method of treating
Parkinson’s and other neurological diseases by grafting brain cells from human fetuses onto the basal
ganglia. Human adults cannot grow new brain cells
but developing fetuses can. Grafting fetal tissue stimulates the growth of new brain cells in affected
adult brains.
Hereditary ataxia—One of a group of hereditary
degenerative diseases of the spinal cord or cerebellum. These diseases cause tremor, spasm, and wasting of muscle.
Huntington’s disease—A rare hereditary condition
that causes progressive chorea (jerky muscle movements) and mental deterioration that ends in dementia. Huntington’s symptoms usually appear in
patients in their 40s. There is no effective treatment.
Levodopa (L-dopa)—A substance used in the treatment of Parkinson’s disease. Levodopa can cross the
blood-brain barrier that protects the brain. Once in
the brain, it is converted to dopamine and thus can
replace the dopamine lost in Parkinson’s disease.

Alternative treatment
There are several alternative therapies that can
be useful when treating movement disorders. The
progress made will depend on the individual and

GALE ENCYCLOPEDIA OF MEDICINE

Positron emission tomography (PET)—A diagnostic
technique in which computer-assisted x rays are
used to track a radioactive substance inside a
patient’s body. PET can be used to study the biochemical activity of the brain.
Progressive supranuclear palsy—A rare disease that
gradually destroys nerve cells in the parts of the
brain that control eye movements, breathing, and
muscle coordination. The loss of nerve cells causes
palsy, or paralysis, that slowly gets worse as the
disease progresses. The palsy affects ability to
move the eyes, relax the muscles, and control
balance.
Restless legs syndrome—A condition that causes an
annoying feeling of tiredness, uneasiness, and itching deep within the muscle of the leg. It is accompanied by twitching and sometimes pain. The only
relief is in walking or moving the legs.
Tourette syndrome—An abnormal condition that
causes uncontrollable facial grimaces and tics and
arm and shoulder movements. Tourette syndrome is
perhaps best known for uncontrollable vocal tics that
include grunts, shouts, and use of obscene language
(coprolalia).
Wilson’s disease—An inborn defect of copper metabolism in which free copper may be deposited in a
variety of areas of the body. Deposits in the brain can
cause tremor and other symptoms of Parkinson’s
disease.

his/her condition. Among the therapies that may
be helpful are acupuncture, homeopathy, touch
therapies, postural alignment therapies, and
biofeedback.
2477

Movement disorders

KEY TERMS

Movement therapy

Prognosis

Description

The prognosis for a patient with a movement disorder depends on the specific disorder.

Prevention
Prevention depends on the specific disorder.
Resources
ORGANIZATIONS

Worldwide Education and Awareness for Movement
Disorders. One Gustave L. Levy Place, Box 1052, New
York, NY 10029. (800) 437-6683. <http://
www.wemove.org>.

Richard Robinson

Movement therapy
Definition
Movement therapy refers to a broad range of
Eastern and Western movement approaches used to
promote physical, mental, emotional, and spiritual
well-being.

Purpose
The physical benefits of movement therapy
include greater ease and range of movement, increased
balance, strength and flexibility, improved muscle
tone and coordination, joint resiliency, cardiovascular
conditioning, enhanced athletic performance, stimulation of circulation, prevention of injuries, greater longevity, pain relief, and relief of rheumatic, neurological,
spinal, stress, and respiratory disorders. Movement
therapy can also be used as a meditation practice to
quiet the mind, foster self-knowledge, and increase
awareness. In addition, movement therapy is beneficial in alleviating emotional distress that is expressed
through the body. These conditions include eating
disorders, excessive clinging, and anxiety attacks.
Since movements are related to thoughts and feelings,
movement therapy can also bring about changes in
attitude and emotions. People report an increase in
self-esteem and self-image. Communication skills can
be enhanced and tolerance of others increased. The
physical openness facilitated by movement therapy
leads to greater emotional openness and creativity.
2478

Origins
Movement is fundamental to human life. In fact
movement is life. Contemporary physics tells us that
the universe and everything in it is in constant motion.
We can move our body and at the most basic level our
body is movement. According to the somatic educator
Thomas Hanna, ‘‘The living body is a moving body—
indeed, it is a constantly moving body.’’ The poet and
philosopher Alan Watts eloquently states a similar
view, ‘‘A living body is not a fixed thing but a flowing
event, like a flame or a whirlpool.’’ Centuries earlier,
the great Western philosopher Socrates understood
what modern physics has proven, ‘‘The universe is
motion and nothing else.’’
Since the beginning of time, indigenous societies
around the world have used movement and dance for
individual and community healing. Movement and
song were used for personal healing, to create community, to ensure successful crops, and to promote fertility. Movement is still an essential part of many
healing traditions and practices throughout the world.
Western movement therapies generally developed
out of the realm of dance. Many of these movement
approaches were created by former dancers or choreographers who were searching for a way to prevent
injury, attempting to recover from an injury, or who
were curious about the effects of new ways of moving.
Some movement therapies arose out of the fields of
physical therapy, psychology, and bodywork. Other
movement therapies were developed as way to treat an
incurable disease or condition.
Eastern movement therapies, such as yoga,
qigong, and t’ai chi began as a spiritual or self-defense
practices and evolved into healing therapies. In China,
for example, Taoist monks learned to use specific
breathing and movement patterns in order to promote
mental clarity, physical strength, and support their
practice of meditation. These practices, later known
as qigong and t’ai chi eventually became recognized as
ways to increase health and prolong life.
There are countless approaches to movement
therapy. Some approaches emphasize awareness and
attention to inner sensations. Other approaches use
movement as a form of psychotherapy, expressing
and working through deep emotional issues. Some
approaches emphasize alignment with gravity and specific movement sequences, while other approaches
encourage spontaneous movement. Some approaches
are primarily concerned with increasing the ease and
efficiency of bodily movement. Other approaches
GALE ENCYCLOPEDIA OF MEDICINE

The term movement therapy is often associated
with dance therapy. Some dance therapists work privately with people who are interested in personal
growth. Others work in mental health settings with
autistic, brain injured and learning disabled children,
the elderly, and disabled adults.
Laban movement analysis (LMA), formerly
known as Effort-Shape is a comprehensive system
for discriminating, describing, analyzing, and categorizing movements. LMA can be applied to dance, athletic coaching, fitness, acting, psychotherapy, and a
variety of other professions. Certified movement analysts can ‘‘observe recurring patterns, note movement
preferences, asses physical blocks and dysfunctional
movement patterns, and the suggest new movement
patterns.’’ As a student of Rudolf Laban, Irmgard
Bartenieff developed his form of movement analysis
into a system of body training or reeducation called
Bartenieff fundamentals (BF). The basic premise of
this work is that once the student experiences a physical foundation, emotional, and intellectual expression
become richer. BF uses specific exercises that are practiced on the floor, sitting, or standing to engage the
deeper muscles of the body and enable a greater range
of movement.
Authentic movement (AM) is based upon Mary
Starks Whitehouse’s understanding of dance, movement, and depth psychology. There is no movement
instruction in AM, simply a mover and a witness. The
mover waits and listens for an impulse to move and then
follows or ‘‘moves with’’ the spontaneous movements
that arise. These movements may or may not be visible
to the witness. The movements may be in response to an
emotion, a dream, a thought, pain, joy, or whatever is
being experienced in the moment. The witness serves as
a compassionate, non judgmental mirror and brings a
‘‘special quality of attention or presence.’’ At the end of
the session the mover and witness speak about their
experiences together. AM is a powerful approach for
self development and awareness and provides access to
preverbal memories, creative ideas, and unconscious
movement patterns that limit growth.
Gabrielle Roth (5 Rhythms movement) and Anna
Halprin have both developed dynamic movement
practices that emphasize personal growth, awareness,
expression, and community. Although fundamentally
different forms, each of these movement/dance
approaches recognize and encourage our inherent
desire for movement.
GALE ENCYCLOPEDIA OF MEDICINE

Several forms of movement therapy grew out of
specific bodywork modalities. Rolfing movement integration (RMI) and Rolfing rhythms are movement
forms which reinforce and help to integrate the structural body changes brought about by the hands-on
work of Rolfing (structural integration). RMI uses a
combination of touch and verbal directions to help
develop greater awareness of one’s vertical alignment
and habitual movement patterns. RMI teacher Mary
Bond says, ‘‘The premise of Rolfing Movement
Integration... is that you can restore your structure
to balance by changing the movement habits that
perpetuate imbalance.’’ Rolfing rhythms is a series of
lively exercises designed to encourage awareness of the
Rolfing principles of ease, length, balance, and harmony with gravity.
The movement education component of AstonPatterning bodywork is called neurokinetics. This
movement therapy teaches ways of moving with
greater ease throughout every day activities. These
movement patterns can also be used to release tension
in the body. Aston fitness is an exercise program
which includes warm-up techniques, exercises to
increase muscle tone and stability, stretching, and cardiovascular fitness.
Rosen method movement (an adjunct to Rosen
method bodywork) consists of simple fun movement
exercises done to music in a group setting. Through
gentle swinging, bouncing, and stretching every joint
in the body experiences a full range of movement. The
movements help to increase balance and rhythm and
create more space for effortless breathing.
The movement form of Trager psychophysical
integration bodywork, Mentastics, consists of fun,
easy swinging, shaking, and stretching movements.
These movements, developed by Dr. Milton Trager,
create an experience of lightness and freedom in the
body, allowing for greater ease in movement. Trager
also worked successfully with polio patients.
Awareness through movement, the movement
therapy form of the Feldenkrais method, consists of
specific structured movement experiences taught as a
group lesson. These lessons reeducate the brain without tiring the muscles. Most lessons are done lying
down on the floor or sitting. Moshe Feldenkrais
designed the lessons to ‘‘improve ability . . . turn the
impossible into the possible, the difficult into the easy,
and the easy into the pleasant.’’
Ideokinesis is another movement approach
emphasizing neuromuscular reeducation. Lulu
Sweigart based her work on the pioneering approach
of her teacher Mabel Elsworth Todd. Ideokinesis uses
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Movement therapy

address the reality of the body ‘‘as movement’’ instead
of the body as only something that runs or walks
through space.

Movement therapy

imagery to train the nervous system to stimulate the
right muscles for the intended movement. If one continues to give the nervous system a clear mental picture
of the movement intended, it will automatically select
the best way to perform the movement. For example,
to enhance balance in standing, Sweigart taught people to visualize ‘‘lines of movement’’ traveling through
their bodies. Sweigart did not train teachers in ideokinesis but some individuals use ideokinetic imagery in
the process of teaching movement.
The Mensendieck system of functional movement
techniques is both corrective and preventative. Bess
Mensendieck, a medical doctor, developed a series of
exercises to reshape, rebuild and revitalize the body.
A student of this approach learns to use the conscious
will to relax muscles and releases tension. There are
more than 200 exercises that emphasize correct and
graceful body movement through everyday activities.
Unlike other movement therapy approaches this work
is done undressed or in a bikini bottom, in front of
mirrors. This allows the student to observe and feel
where a movement originates. Success has been reported
with many conditions including Parkinson’s disease,
muscle and joint injuries, and repetitive strain injuries.
The Alexander technique is another functional
approach to movement therapy. In this approach a
teacher gently uses hands and verbal directions to
subtly guide the student through movements such as
sitting, standing up, bending and walking. The
Alexander technique emphasizes balance in the neckhead relationship. A teacher lightly steers the students
head into the proper balance on the tip of the spine
while the student is moving in ordinary ways. The
student learns to respond to movement demands
with the whole body, in a light integrated way. This
approach to movement is particularly popular with
actors and other performers.
Pilates or physical mind method is also popular
with actors, dancers, athletes, and a broad range of
other people. Pilates consists of over 500 exercises
done on the floor or primarily with customized exercise equipment. The exercises combine sensory awareness and physical training. Students learn to move
from a stable, central core. The exercises promote
strength, flexibility, and balance. Pilates training is
increasingly available in sports medicine clinics, fitness
centers, dance schools, spas, and physical therapy
offices.
Many approaches to movement therapy emphasize awareness of internal sensations. Charlotte Selver,
a student of somatic pioneer Elsa Gindler, calls her
style of teaching sensory awareness (SA). This
2480

approach has influenced the thinking of many innovators, including Fritz Perls, who developed gestalt
therapy. Rather than suggesting a series of structured
movements, visualizations, or body positions, in SA
the teacher outlines experiments in which one can
become aware of the sensations involved in any movement. A teacher might ask the student to feel the
movement of her breathing while running, sitting,
picking up a book, etc. This close attunement to
inner sensory experience encourages an experience of
body-mind unity in which breathing becomes less
restricted and posture, coordination, flexibility, and
balance are improved. There may also be the experience of increased energy and aliveness.
Gerda Alexander Eutony (GAE) is another movement therapy approach that is based upon internal
awareness. Through GAE one becomes a master of
self-sensing and knowing which includes becoming
sensitive to the external environment, as well. For
example, while lying on the floor sensing the breath,
skin or form of the body, one also senses the connection with the ground. GAE is taught in group classes
or private lessons which also include hands-on therapy. In 1987, after two years of observation in clinics
throughout the world, GAE became the first mindbody discipline accepted by the World Health
Organization (WHO) as an alternative health-care
technique.
Kinetic awareness developed by dancer-choreographer Elaine Summers, emphasizes emotional and
physical inquiry. Privately or in a group, a teacher sets
up situations for the student to explore the possible
causes of pain and movement restrictions within the
body. Rubber balls of various sizes are used as props
to focus attention inward, support the body in a
stretched position and massage a specific area of the
body. The work helps one to deal with chronic pain,
move easily again after injuries and increase energy,
flexibility, coordination, and comfort.
Body-mind centering (BMC) was developed by
Bonnie Bainbridge Cohen and is a comprehensive
educational and therapeutic approach to movement.
BMC practitioners use movement, touch, guided imagery, developmental repatterning, dialogue, music,
large balls, and other props in an individual session
to meet the needs of each person. BMC encourages
people to develop a sensate awareness and experience
of the ligaments, nerves, muscles, skin, fluids, organs,
glands, fat, and fascia that make up one’s body. It has
been effective in preventing and rehabilitating from
chronic injuries and in improving neuromuscular
response in children with cerebral palsy and other
neurological disorders.
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Eastern movement therapies such as yoga, t’ai
chi, and qigong are also effective in healing and preventing a wide range of physical disorders, encouraging emotional stability, and enhancing spiritual
awareness. There are a number of different
approaches to yoga. Some emphasize the development of physical strength, flexibility, and alignment.
Other forms of yoga emphasize inner awareness,
opening, and meditation.

Precautions
People with acute injuries and chronic physical
and mental conditions need to be careful when choosing a form of movement therapy. It is best to consult
with a knowledgeable physician, physical therapist, or
mental health therapist.
A special form of movement therapy known as
constraint-induced movement therapy, or CIMT, is
being used as of the early 2000s to rehabilitate the
upper limbs of patients who have suffered a stroke,
traumatic brain injury, or damage to the spinal cord.
In CIMT, the arm that has been less affected by the
injury is constrained by a sling for 90% of the patient’s
waking hours for a period of two weeks. The sling
forces the patient to use the weaker arm more often;
in addition, a physical therapist works with the patient
to practice repetitive motions with the weaker arm.
CIMT also appears to be useful in treating children
with muscular weakness on one side of the body
caused by cerebral palsy.

Research and general acceptance
Although research has documented the beneficial
effects of dance therapy, qigong, t’ai chi, yoga,
Alexander technique, awareness through movement
(Feldenkrais), and Rolfing, other forms of movement
therapy have not been as thoroughly researched.
GALE ENCYCLOPEDIA OF MEDICINE

CIMT has become widely accepted in rehabilitation medicine since its introduction in the mid-1990s,
although some doctors still consider it experimental.
Further research in CIMT is being carried out by the
National Institute of Neurological Disorders and
Stroke (NINDS), one of the National Institutes of
Health.
Resources
BOOKS

Halprin, Anna. Dance as a Healing Art: Returning to Health
Through Movement and Imagery. Life Rhythm, 1999.
PERIODICALS

Bunch, W. ‘‘Dancing through the Pain. Physician Executive
Launches New Business to Treat Patients with Chronic
Pain.’’ Physician Executive 30 (January-February
2004): 30–33.
Cottingham, John T., and Jeffrey Maitland. ‘‘Integrating
Manual and Movement Therapy With Philosophical
Counseling for Treatment of a Patient With
Amyotrophic Lateral Sclerosis: A Case Study That
Explores the Principles of Holistic Intervention.’’
Alternative Therapies Journal March 2000: 120-128.
Mark, V. W., and E. Taub. ‘‘Constraint-Induced Movement
Therapy for Chronic Stroke Hemiparesis and Other
Disabilities.’’ Restorative Neurology and Neuroscience
22 (March 2004): 317–336.
Page, S. J., S. Sisto, P. Levine, and R. E. McGrath. ‘‘Efficacy
of Modified Constraint-Induced Movement Therapy in
Chronic Stroke: A Single-Blinded Randomized
Controlled Trial.’’ Archives of Physical Medicine and
Rehabilitation 85 (January 2004): 14–18.
Taub, E., S. L. Ramey, S. DeLuca, and K. Echols. ‘‘Efficacy
of Constraint-Induced Movement Therapy for
Children with Cerebral Palsy with Asymmetric Motor
Impairment.’’ Pediatrics 113 (February 2004): 305–312.
ORGANIZATIONS

National Institute of Neurological Disorders and Stroke
(NINDS). NIH Neurological Institute, P. O. Box 5801,
Bethesda, MD 20824. (800) 352-9424 or (301) 4965751.< http://www.ninds.nih.gov>.

Linda Chrisman
Rebecca J. Frey, PhD

Mpell disease see Ankylosing spondylitis
MR see Magnetic resonance imaging
MRI see Magnetic resonance imaging
MS see Multiple sclerosis
M’s disease see Waldenström’s
macroglobulinemia
2481

Movement therapy

Continuum movement has also been shown to be
effective in treating neurological disorders including
spinal chord injury. Developed by Emilie Conrad and
Susan Harper, continuum movement is an inquiry into
the creative flux of our body and all of life. Sound,
breath, subtle and dynamic movements are explored
that stimulate the brain and increase resonance with
the fluid world of movement. The emphasis is upon
unpredictable, spontaneous or spiral movements
rather than a linear movement pattern. According to
Conrad, ‘‘Awareness changes how we physically
move. As we become more fluid and resilient so do
the mental, emotional, and spiritual movements of our
lives.’’

Mucopolysaccharidoses

Mucopolysaccharidoses
Definition
Mucopolysaccharidosis (MPS) is a general term
for a number of inherited diseases that are caused by
the accumulation of mucopolysaccharides, resulting in
problems with an individual’s development. With each
condition, mucopolysaccharides accumulate in the
cells and tissues of the body because of a deficiency
of a specific enzyme. The specific enzyme that is deficient or absent is what distinguishes one type of MPS
from another. However, before these enzymes were
identified, the MPS disorders were diagnosed by the
signs and symptoms that an individual expressed. The
discovery of these enzymes resulted in a reclassification of some of the MPS disorders. These conditions
are often referred to as MPS I, MPS II, MPS III, MPS
IV, MPS VI, MPS VII, and MPS IX. However, these
conditions are also referred to by their original names,
which are Hurler, Hurler-Scheie, Scheie (all MPS I),
Hunter (MPS II), Sanfilippo (MPS III), Morquio
(MPS IV), Maroteaux-Lamy (MPS VI), Sly (MPS
VII), and Hyaluronidase deficiency (MPS IX).

Description
Mucopolysaccharides are long chains of sugar
molecules that are essential for building the bones,
cartilage, skin, tendons, and other tissues in the
body. Normally, the human body continuously breaks
down and builds mucopolysaccharides. Another name
for mucopolysaccharides is glycosaminoglycans
(GAGs). There are many different types of GAGs
and specific GAGs are unable to be broken down in
each of the MPS conditions. There are several enzymes
involved in breaking down each GAG and a deficiency
or absence of any of the essential enzymes can cause
the GAG to not be broken down completely and result
in its accumulation in the tissues and organs in the
body. In some MPS conditions, in addition to the
GAG being stored in the body, some of the incompletely broken down GAGs can leave the body via the
urine. When too much GAG is stored, organs and
tissues can be damaged or not function properly.
Genetic profile
Except for MPS II, the MPS conditions are inherited in an autosomal recessive manner. MPS conditions occur when both of an individual’s genes that
produce the specific enzyme contain a mutation, causing them to not work properly. When both genes do
not work properly, either none or a reduced amount of
2482

the enzyme is produced. An individual with an autosomal recessive condition inherits one of those nonworking genes from each parent. These parents are
called ‘‘carriers’’ of the condition. When two people
are known carriers for an autosomal recessive condition, they have a 25% chance with each pregnancy to
have a child affected with the disease. Some individuals with MPS do have children of their own.
Children of parents who have an autosomal recessive
condition are all carriers of that condition. These children are not at risk to develop the condition unless the
other parent is a carrier or affected with the same
autosomal recessive condition.
Unlike the other MPS conditions, MPS II is inherited in an X-linked recessive manner. This means that
the gene causing the condition is located on the
X chromosome, one of the two sex chromosomes.
Since a male has only one X chromosome, he will
have the disease if the X chromosome inherited from
his mother carries the defective gene. Females, because
they have two X chromosomes, are called ‘‘carriers’’ of
the condition if only one of their X chromosomes has
the gene that causes the condition, while the other X
chromosome does not.

Causes and symptoms
Each type of MPS is caused by a deficiency of one
of the enzymes involved in breaking down GAGs. It is
the accumulation of the GAGs in the tissues and
organs in the body that cause the wide array of symptoms characteristic of the MPS conditions. The accumulating material is stored in cellular structures called
lysosomes, and these disorders are also known as lysosomal storage diseases.
MPS I
MPS I is caused by a deficiency of the enzyme
alpha-L-iduronidase. Three conditions, Hurler,
Hurler-Scheie, and Scheie syndromes, all are caused
by a deficiency of this enzyme. Initially, these three
conditions were felt to be separate because each were
associated with different physical symptoms and prognoses. However, once the underlying cause of these
conditions was identified, it was realized that these
three conditions were all variants of the same disorder.
The gene involved with MPS I is located on chromosome 4p16.3.
MPS I H (HURLER SYNDROME). It has been estimated that approximately one baby in 100,000 will
be born with Hurler syndrome. Individuals with
Hurler syndrome tend to have the most severe form
of MPS I. Symptoms of Hurler syndrome are often

GALE ENCYCLOPEDIA OF MEDICINE

MPS I H/S (HURLER-SCHEIE SYNDROME). HurlerScheie syndrome is felt to be the intermediate form
of MPS I, meaning that the symptoms are not as severe
as those in individuals who have MPS I H but not as
mild as those in MPS I S. Approximately one baby in
115,000 will be born with Hurler-Scheie syndrome.
These individuals tend to be shorter than expected,
and they can have normal intelligence, however,
some individuals with MPS I H/S will experience
learning difficulties. These individuals may develop
some of the same physical features as those with
Hurler syndrome, but usually they are not as severe.
The prognosis for children with MPS I H/S is variable
with some individuals dying during childhood, while
others living to adulthood.
MPS I S (SCHEIE SYNDROME). Scheie syndrome is
considered the mild form of MPS I. It is estimated
that approximately one baby in 500,000 will be born
with Scheie syndrome. Individuals with MPS I S
usually have normal intelligence, but there have been
some reports of individuals with MPS I S developing
psychiatric problems. Common physical problems
include corneal clouding, heart abnormalities, and
orthopedic difficulties involving their hands and
back. Individuals with MPS I S do not develop the
facial features seen with MPS I H and usually these
individuals have a normal life span.

MPS II (Hunter syndrome)
Hunter syndrome is caused by a deficiency of the
enzyme iduronate-2-sulphatase. All individuals with
Hunter syndrome are male, because the gene that
GALE ENCYCLOPEDIA OF MEDICINE

causes the condition is located on the X chromosome,
specifically Xq28. Like many MPS conditions, Hunter
syndrome is divided into two groups, mild and severe.
It has been estimated that approximately 1 in 110,000
males are born with Hunter syndrome, with the severe
form being three times more common than the mild
form. The severe form is felt to be associated with
progressive mental retardation and physical disability,
with most individuals dying before age 15. In the
milder form, most of these individuals live to adulthood and have normal intelligence or only mild mental
impairments. Males with the mild form of Hunter
syndrome develop physical differences similar to the
males with the severe form, but not as quickly. Men
with mild Hunter syndrome can have a normal life
span and some have had children. Most males with
Hunter syndrome develop joint stiffness, chronic diarrhea, enlarged liver and spleen, heart valve problems,
hearing loss, kyphosis, and tend to be shorter than
expected. These symptoms tend to progress at a different rate depending on if an individual has the mild
or severe form of MPS II.
MPS III (Sanfilippo syndrome)
MPS III, like the other MPS conditions, was initially diagnosed by the individual having certain physical characteristics. It was later discovered that the
physical symptoms associated with Sanfilippo syndrome could be caused by a deficiency in one of four
enzymes. Each type of MPS III is now subdivided into
four groups, labeled A-D, based on the specific
enzyme that is deficient. All four of these enzymes
are involved in breaking down the same GAG,
heparan sulfate. Heparan sulfate is mainly found in
the central nervous system and accumulates in the
brain when it cannot be broken down because one of
those four enzymes are deficient or missing.
MPS III is a variable condition with symptoms
beginning to appear between ages two and six years of
age. Because of the accumulation of heparan sulfate in
the central nervous system, the central nervous system
is severely affected. In MPS III, signs that the central
nervous system is degenerating usually are evident in
most individuals between ages six and 10. Many children with MPS III will develop seizures, sleeplessness,
thicker skin, joint contractures, enlarged tongues, cardiomyopathy, behavior problems, and mental retardation. The life expectancy in MPS III is also variable.
On average, individuals with MPS III live until they
are teenagers, with some living longer and others not
that long.
MPS IIIA (SANFILIPPO SYNDROME TYPE A). MPS
IIIA is caused by a deficiency of the enzyme heparan

2483

Mucopolysaccharidoses

evident within the first year or two after birth. Often
these infants begin to develop as expected, but then
reach a point where they begin to loose the skills that
they have learned. Many of these infants may initially
grow faster than expected, but their growth slows and
typically stops by age three. Facial features also begin
to appear ‘‘coarse.’’ They develop a short nose, flatter
face, thicker skin, and a protruding tongue.
Additionally, their heads become larger and they
develop more hair on their bodies with the hair becoming coarser. Their bones are also affected, with these
children usually developing joint contractures (stiff
joints), kyphosis (a specific type of curve to the
spine), and broad hands with short fingers. Many of
these children experience breathing difficulties, and
respiratory infections are common. Other common
problems include heart valve dysfunction, thickening
of the heart muscle (cardiomyopathy), enlarged spleen
and liver, clouding of the cornea, hearing loss, and
carpal tunnel syndrome. These children typically do
not live past age 12.

Mucopolysaccharidoses

N-sulfatase. Type IIIA is felt to be the most severe of
the four types, in which symptoms appear and death
occurs at an earlier age. A study in British Columbia
estimated that one in 324,617 live births are born with
MPS IIIA. MPS IIIA is the most common of the four
types in Northwestern Europe. The gene that causes
MPS IIIA is located on the long arm of chromosome
17 (location 17q25).
MPS IIIB (SANFILIPPO SYNDROME TYPE B). MPS IIIB

is due to a deficiency in N-acetyl-alpha-D-glucosaminidase (NAG). This type of MPS III is not felt to be as
severe as Type IIIA and the characteristics vary. Type
IIIB is the most common of the four in southeastern
Europe. The gene associated with MPS IIIB is also
located on the long arm of chromosome 17 (location
17q21).
MPS IIIC (SANFILIPPO SYNDROME TYPE C). A deficiency in the enzyme acetyl-CoA-alpha-glucosaminide
acetyltransferase causes MPS IIIC. This is considered
a rare form of MPS III. The gene involved in MPS
IIIC is believed to be located on chromosome 14.
MPS IIID (SANFILIPPO SYNDROME TYPE D). MPS
IIID is caused by a deficiency in the enzyme N-acetylglucosamine-6-sulfatase. This form of MPS III is
also rare. The gene involved in MPS IIID is located on
the long arm of chromosome 12 (location 12q14).

MPS IV (Morquio syndrome)
As with several of the MPS disorders, Morquio
syndrome was diagnosed by the presence of particular
signs and symptoms. However, it is now known that
the deficiency of two different enzymes can cause the
characteristics of MPS IV. These two types of MPS IV
are called MPS IV A and MPS IV B. MPS IV is also
variable in its severity. The intelligence of individuals
with MPS IV is often completely normal. In individuals with a severe form, skeletal abnormalities can be
extreme and include dwarfism, kyphosis (backwardcurved spine), prominent breastbone, flat feet, and
knock-knees. One of the earliest symptoms seen in
this condition usually is a difference in the way the
child walks. In individuals with a mild form of MPS
IV, limb stiffness, and joint pain are the primary symptoms. MPS IV is one of the rarest MPS disorders, with
approximately one baby in 300,000 born with this
condition.
MPS IV A (MORQUIO SYNDROME TYPE A). MPS IV
A is the ‘‘classic’’ or the severe form of the condition
and is caused by a deficiency in the enzyme galactosamine-6-sulphatase. The gene involved with MPS IV A
is located on the long arm of chromosome 16 (location
16q24.3).

2484

MPS IV B (MORQUIO SYNDROME TYPE B). MPS IV B
is considered the milder form of the condition. The
enzyme, beta-galactosidase, is deficient in MPS IV B.
The location of the gene that produces beta-galactosidase is located on the short arm of chromosome 3
(location 3p21).

MPS VI (Maroteaux-Lamy syndrome)
MPS VI, which is another rare form of MPS, is
caused by a deficiency of the enzyme N-acetylglucosamine-4-sulphatase. This condition is also variable;
individuals may have a mild or severe form of the
condition. Typically, the nervous system or intelligence of an individual with MPS VI is not affected.
Individuals with a more severe form of MPS VI can
have airway obstruction, develop hydrocephalus (extra
fluid accumulating in the brain) and have bone
changes. Additionally, individuals with a severe form
of MPS VI are more likely to die while in their teens.
With a milder form of the condition, individuals tend
to be shorter than expected for their age, develop
corneal clouding, and live longer. The gene involved
in MPS VI is believed to be located on the long arm of
chromosome 5 (approximate location 5q11-13).
MPS VII (Sly syndrome)
MPS VII is an extremely rare form of MPS and is
caused by a deficiency of the enzyme beta-glucuronidase. It is also highly variable, but symptoms are generally similar to those seen in individuals with Hurler
syndrome. The gene that causes MPS VII is located on
the long arm of chromosome 7 (location 7q21).
MPS IX (Hyaluronidase deficiency)
MPS IX is a condition that was first described
in 1996 and has been grouped with the other MPS
conditions by some researchers. MPS IX is caused
by the deficiency of the enzyme hyaluronidase. In
the few individuals described with this condition,
the symptoms are variable, but some develop softtissue masses (growths under the skin). Also, these
individuals are shorter than expected for their age.
The gene involved in MPS IX is believed to be
located on the short arm of chromosome 3 (possibly
3p21.3-21.2)
Many individuals with an MPS condition have
problems with airway constriction. This constriction
may be so serious as to create significant difficulties in
administering general anesthesia. Therefore, it is
recommended that surgical procedures be performed
under local anesthesia whenever possible.
GALE ENCYCLOPEDIA OF MEDICINE

Cardiomyopathy—A thickening of the heart
muscle.
Enzyme—A protein that catalyzes a biochemical
reaction or change without changing its own structure or function.
Joint contractures—Stiffness of the joints that prevents full extension.
Kyphosis—An abnormal outward curvature of the
spine, with a hump at the upper back.
Lysosome—Membrane-enclosed compartment in
cells, containing many hydrolytic enzymes; where
large molecules and cellular components are broken down.
Mucopolysaccharide—A complex molecule made
of smaller sugar molecules strung together to form a
chain. Found in mucous secretions and intercellular spaces.
Recessive gene—A type of gene that is not
expressed as a trait unless inherited by both parents.
X-linked gene—A gene carried on the X chromosome, one of the two sex chromosomes.

There is no cure for mucopolysaccharidosis.
There are several types of experimental therapies that
are being investigated. Typically, treatment involves
trying to relieve some of the symptoms. For MPS I and
VI, bone marrow transplantation has been attempted as
a treatment option. In those conditions, bone marrow
transplantation has sometimes been found to help
slow down the progression or reverse some of symptoms of the disorder in some children. The benefits of a
bone marrow transplantation are more likely to be
noticed when performed on children under two years
of age. However it is not certain that a bone marrow
transplant can prevent further damage to certain
organs and tissues, including the brain. Furthermore,
bone marrow transplantation is not felt to be helpful
in some MPS disorders and there are risks, benefits,
and limitations with this procedure. In 2000, ten individuals with MPS I received recombinant human
alpha-L-iduronidase every week for one year. Those
individuals showed an improvement with some of
their symptoms. Additionally, there is ongoing
research involving gene replacement therapy (the
insertion of normal copies of a gene into the cells of
patients whose gene copies are defective).

Prevention
Diagnosis
While a diagnosis for each type of MPS can be
made on the basis of the physical signs described
above, several of the conditions have similar features.
Therefore, enzyme analysis is used to determine the
specific MPS disorder. Enzyme analysis usually cannot accurately determine if an individual is a carrier
for a MPS condition. This is because the enzyme levels
in individuals who are not carriers overlaps the
enzyme levels seen in those individuals who are carrier
for a MPS. With many of the MPS conditions, several
mutations have been found in each gene involved that
can cause symptoms of each condition. If the specific
mutation is known in a family, DNA analysis may be
possible.
Once a couple has had a child with an MPS condition, prenatal diagnosis is available to them to help
determine if a fetus is affected with the same MPS as
their other child. This can be accomplished through
testing samples using procedures such as an amniocentesis or chorionic villus sampling (CVS). Each of
these procedures has its own risks, benefits, and
limitations.
GALE ENCYCLOPEDIA OF MEDICINE

No specific preventive measures are available for
genetic diseases of this type. For some of the MPS
diseases, biochemical tests are available that will identify healthy individuals who are carriers of the defective gene, allowing them to make informed
reproductive decisions. There is also the availability
of prenatal diagnosis for all MPS disease to detect
affected fetuses.
Resources
PERIODICALS

Caillud, C., and L. Poenaru. ‘‘Gene Therapy in Lysosomal
Diseases.’’ Biomed & Pharmacother 54 (2000): 505–512.
Kakkis, E. D., et al. ‘‘Enzyme-Replacement Therapy in
Mucopolysaccharidosis I.’’ The New England Journal of
Medicine 344 (2001): 182–188.
ORGANIZATIONS

Canadian Society for Mucopolysaccharide and Related
Diseases. PO Box 64714, Unionville, ONT L3R-OM9.
Canada (905) 479-8701 or (800) 667-1846. <http://
www.mpssociety.ca>.
Children Living with Inherited Metabolic Diseases. The
Quadrangle, Crewe Hall, Weston Rd., Crewe, Cheshire,
CW1-6UR. UK 127 025 0221. Fax: 0870-7700-327.
<http://www.climb.org.uk>.
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Treatment

KEY TERMS

Mucormycosis

Metabolic Information Network. PO Box 670847, Dallas,
TX 75367-0847. (214) 696-2188 or (800) 945-2188.
National MPS Society. 102 Aspen Dr., Downingtown, PA
19335. (610) 942-0100. Fax: (610) 942-7188.
info@mpssociety.org. <http://www.mpssociety.org>.
National Organization for Rare Disorders (NORD). PO
Box 8923, New Fairfield, CT 06812-8923. (203) 7466518 or (800) 999-6673. Fax: (203) 746-6481. <http://
www.rarediseases.org>.
Society for Mucopolysaccharide Diseases. 46 Woodside
Rd., Amersham, Buckinghamshire, HP6 6AJ. UK +44
(01494) 434156. <http://www.mpssociety.co.uk>.
Zain Hansen MPS Foundation. 23400 Henderson Rd.,
Covelo, CA 95420. (800) 767-3121.
OTHER

National Library of Medicine. National Institutes of Health.
<http://www.nlm.nih.gov/>.
‘‘NINDS Mucopolysaccharidoses Information Page.’’ The
National Institute of Neurological Disorders and
Stroke. National Institutes of Health. <http://
www.ninds.nih.gov/health_and_medical/disorders/
mucopolysaccharidoses.htm>.
Online Mendelian Inheritance in Man (OMIM). National
Center for Biotechnology Information. <http://
www.ncbi.nlm.nih.gov/Omim/>.

Sharon A. Aufox, MS, CGC

Mucormycosis
Definition
Mucormycosis is a rare but often fatal disease
caused by certain fungi. It is sometimes called zygomycosis or phycomycosis. Mucormycosis is an opportunistic infection that typically develops in patients
with weakened immune systems, diabetes, kidney failure, organ transplants, or chemotherapy for cancer. It
may also develop in patients receiving an iron chelating drug called desferrioxamine (Desferal) as treatment for acute iron poisoning.

Description
In the United States, mucormycosis is most likely
to develop in the patient’s nasal area or in the lungs;
however, it may also develop on the skin or in the
digestive tract. Gastrointestinal disease usually develops only in severely malnourished patients. Cutaneous
mucormycosis is most likely to develop under occlusive surgical dressings. Occlusive dressings are
2486

intended to keep air out of incisions or other wounds,
but they also trap body heat and moisture.
The incidence of the disease is difficult to evaluate
because it is very rare; however, the rate seems to be
increasing. One American cancer center reported in
2000 that mucormycosis was found in 0.7% of patients
at autopsy and in 20 patients per 100,000 admissions to
the center. The most recent mortality statistics from
the Centers for Disease Control and Prevention
(CDC) indicate that a total of 22 Americans died
from mucormycosis in 2001—1 from pulmonary
mucormycosis, 5 from rhinocerebral mucormycosis,
2 from disseminated mucormycosis, and 14 from
unspecified forms of the disease.
As far as is known, mucormycosis affects members of either sex and all races equally, although the
pulmonary form of the disease is somewhat more
common in men than in women. Mucormycosis may
develop in patients in any age group, including
newborns.
Rhinocerebral mucormycosis
Rhinocerebral mucormycosis is an infection of the
nose, eyes, and brain. The fungus destroys the tissue of
the nasal passages, sinuses, or hard palate, producing
a black or pus-filled discharge and visible patches of
dying tissue. The patient will typically have fever, pain,
and forward bulging of the eyes (proptosis). The fungus then invades the tissues around the eye socket and
eventually the brain. At that point the patient may
have convulsions or paralysis on one side of the body.
Pulmonary mucormycosis
Most patients with the pulmonary form of the
disease are being treated for leukemia. The fungus
enters the patient’s lungs, where it eventually invades
a major blood vessel, causing the patient to cough up
blood or hemorrhage into the lungs.
Gastrointestinal mucormycosis
Gastrointestinal mucormycosis has been reported
in premature or low-birth-weight infants as well as
malnourished adults. It may lead to intestinal perforation and other complications requiring immediate surgery. A Spanish hospital reported in 2004 on an
outbreak of gastrointestinal mucormycosis that
affected five patients in an ICU over a 14-week period.
Two of the patients died. The outbreak was eventually
traced to a supply of wooden tongue depressors that
had been contaminated by two species of Rhizopus
fungi.
GALE ENCYCLOPEDIA OF MEDICINE

Mucormycosis is caused by fungi of several different species, including Mucor, Rhizopus, Absidia, and
Rhizomucor. When these organisms gain access to the
mucous membranes of the patient’s nose or lungs, they
multiply rapidly and invade the nearby blood vessels.
The fungi destroy soft tissue and bone, as well as the
walls of blood vessels.
The early symptoms of rhinocerebral mucormycosis include fever, sinus pain, headache, and cellulitis. As
the fungus reaches the eye tissues, the patient develops
dilated pupils, drooping eyelids, a bulging eye, and
eventually hemorrhage of the blood vessels in the
brain– causing convulsions, partial paralysis, and death.
The symptoms of pulmonary mucormycosis
include fever and difficulty breathing, with eventual
bleeding from the lungs.
The symptoms of gastrointestinal mucormycosis
are not unique to the disease, which may complicate
diagnosis. Patients typically complain of pressure or
pain in the abdomen, nausea, and vomiting.

KEY TERMS
Amphotericin B—An antibiotic used to treat
mucormycosis and other severe fungal infections.
Opportunistic infection—An infection that develops only when a person’s immune system is
weakened.
Orbit—The bony cavity or socket surrounding the
eye.
Zygomycosis—Another term for mucormycosis.
The fungi that cause mucormycosis belong to a
group called Zygomycetes.

facial swelling and a black discharge from the nose—
and telling them to see a doctor at once if they notice
these symptoms.
Patients who survive rhinocerebral mucormycosis
are often left with severe facial disfigurement and
usually require plastic surgery to restore their
appearance.

Diagnosis
Diagnosis is usually based on a combination of
the patient’s medical history and a visual examination
of the nose, throat, and eyes. The doctor will take a
tissue sample for biopsy, or a PAS, potassium hydroxide (KOH), or Calcofluor stain in order to make a
tentative diagnosis. Confirmation requires a laboratory culture.
Imaging studies are not needed to make the diagnosis. If the patient has mucormycosis, however, magnetic resonance imaging (MRI) and computed
tomography scans (CT scans) will usually show the
destruction of soft tissue or bone in patients with
advanced disease. Chest x rays will sometimes show a
cavity in the lung or an area filled with tissue fluid if
the patient has pulmonary mucormycosis.

Treatment
Treatment is usually begun without waiting for
laboratory reports because of the rapid spread and
high mortality rate of the disease. Therapy includes
intravenous amphotericin B (Fungizone); surgical
removal of infected tissue; and careful monitoring of
the disorder or condition that is responsible for the
patient’s vulnerability. Most patients who survive
require a 4–6-week course of treatment.
Follow-up care includes educating patients about
the signs of recurrent mucormycosis—particularly
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The prognosis for recovery from mucormycosis is
poor. The mortality rate is 30%–50% of patients with
the rhinocerebral form, and even higher for patients
with pulmonary mucormycosis. The disease is almost
100% fatal for patients with AIDS.

Prevention
Prevention depends on protecting high-risk
patients from contact with sugary foods, decaying
plants, moldy bread, manure, and other breeding
grounds for fungi. In addition, health care professionals treating hospital inpatients should be careful
to change occlusive dressings frequently and check the
underlying skin for any signs of possible fungal
infection.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Mucormycosis.’’ Section 13, Chapter 158. In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Eisen, Damon, MD. ‘‘Mucormycosis.’’ eMedicine
December10, 2001. <http://www.emedicine.com/med/
topic1513.htm>.
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Causes and symptoms

Multiple-gated acquisition (MUGA) scan

Maravi-Poma, E., J. L. Rodriguez-Tudela, J. G. de Jalon, et
al. ‘‘Outbreak of Gastric Mucormycosis Associated
with the Use of Wooden Tongue Depressors in
Critically Ill Patients.’’ Intensive Care Medicine 30
(April 2004): 724–728.
Numa, W. A., Jr, P. K. Foster, J. Wachholz, et al.
‘‘Cutaneous Mucormycosis of the Head and Neck with
Parotid Gland Involvement: First Report of a Case.’’
Ear, Nose, and Throat Journal 83 (April 2004): 282–286.
Siu, K. L., and W. H. Lee. ‘‘A Rare Cause of Intestinal
Perforation in an Extreme Low Birth Weight Infant—
Gastrointestinal Mucormycosis: A Case Report.’’
Journal of Perinatology 24 (May 2004): 319–321.
Wolf, O., Z. Gil, L. Leider-Trejo, et al. ‘‘Tracheal
Mucormycosis Presented as an Intraluminal Soft Tissue
Mass.’’ Head and Neck 26 (June 2004): 541–543.
ORGANIZATIONS

Centers for Disease Control. 1600 Clifton Rd., NE, Atlanta,
GA 30333. (800) 311-3435, (404) 639-3311. <http://
www.cdc.gov>.

Rebecca J. Frey, PhD

Mucoviscidosis see Cystic fibrosis
MUGA scan see Multiple-gated acquisition
(MUGA) scan

Multiple-gated acquisition
(MUGA) scan
Definition
The multiple-gated acquisition (MUGA) scan is a
non-invasive nuclear test that uses a radioactive isotope called technetium to evaluate the functioning of
the heart’s ventricles.

Purpose
The MUGA scan is performed to determine if the
heart’s left and right ventricles are functioning properly and to diagnose abnormalities in the heart wall. It
can be ordered in the following patients:


With known or suspected coronary artery disease, to
diagnose the disease and predict outcomes



With lesions in their heart valves



Who have recently had a heart attack, to assess
damage to heart tissue and predict the likelihood of
future cardiac events



With congestive heart failure

2488



Who have undergone percutaneous transluminal
coronary angioplasty, coronary artery bypass graft
surgery, or medical therapy, to assess the efficacy of
the treatment



With low cardiac output after open-heart surgery



Who are undergoing chemotherapy.

Precautions
Pregnant women and those who are breastfeeding
should not be exposed to technetium.

Description
The MUGA scan measures the heart’s function
and the flow of blood through it. The strongest chamber in the heart is the left ventricle, which serves as the
main pump of blood through the body. The left ventricular is assessed by measuring the amount of blood
pumped with each heartbeat (the ejection fraction),
ventricle filling, and the blood flow into the pumping
chamber. A normal ejection fraction is 50% or more.
The heart’s ejection fraction is one of the most important measures of its performance. The right ventricle’s
ability to pump blood to the lungs is also assessed, and
any abnormalities in the heart wall are identified. The
MUGA scan is the most accurate, non-invasive test
available to assess the heart’s ventricles.
MUGA is a nuclear heart scan, which means that
it involves the use of a radioactive isotope that targets
the heart and a radionuclide detector that traces the
absorption of the radioactive isotope. The isotope is
injected into a vein and absorbed by healthy tissue at a
known rate during a certain time period. The radionuclide detector, in this case a gamma scintillation
camera, picks up the gamma rays emitted by the
isotope.
During the MUGA scan, electrodes are placed on
the patient’s body so that an electrocardiogram (ECG)
can be conducted. The imaging equipment and computer are synchronized with the ECG so that images of
the heart can be recorded without motion or blur.
Then a small amount of a mildly radioactive isotope
called technetium Tc99m stannous pyrophosphate,
usually called technetium, is injected, usually into an
arm vein. While the patient lies motionless on the test
table, a gamma scintillation camera follows the movement of the technetium through the blood circulating
in the heart. The camera, which looks like an x-ray
machine and is suspended above the table, moves back
and forth over the patient. It displays multiple images
of the heart in motion and records them on a computer
for later analysis.
GALE ENCYCLOPEDIA OF MEDICINE

The MUGA scan can be done with the patient at
rest or exercising (called a stress MUGA). The stress
MUGA is often performed in patients who have or are
suspected of having coronary artery disease. The resting MUGA is compared to the stress MUGA and
changes in the heart’s pumping performance are analyzed. In some cases, the rest MUGA is compared to a
nitroglycerin MUGA, in which a strong heart drug
called nitroglycerin is administered to the patient
before the scan. For the nitroglycerin MUGA, a cardiologist should be present.
The MUGA scan is not dangerous. The technetium is completely gone from the body within a few
days of the test. The scan itself exposes the patient to
about the same amount of radiation as a chest x ray.
The patient can resume normal activities immediately
after the test.

Normal results
If the patient’s heart is normal, the technetium will
appear to be evenly distributed in the scans. In a stress
MUGA, patients with normal hearts will exhibit an
increase in ejection fraction or no change.

Abnormal results
An uneven distribution of technetium in the heart
indicates that the patient has coronary artery disease,
a cardiomyopathy, or blood shunting within the heart.
Abnormalities in a resting MUGA usually indicate a
heart attack, while those that occur during exercise
usually indicate ischemia. In a stress MUGA, patients
with coronary artery disease may exhibit a decrease in
ejection fraction.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Ejection fraction—The fraction of all blood in the
ventricle that is ejected at each heartbeat. One of
the main advantages of the MUGA scan is its ability
to measure ejection fraction, one of the most
important measures of the heart’s performance.
Electrocardiogram—A test in which electronic
sensors called electrodes are placed on the body
to record the heart’s electrical activities.
Heart attack—A cardiac emergency that occurs
when a clot blocks blood flow in one or more of
the heart’s arteries. Oxygen supply to the heart
muscle is cut off, resulting in the death of heart
tissue in the affected area.
Ischemia—A decreased supply of oxygenated blood
to a body part or organ, often marked by pain and
organ dysfunction, as in ischemic heart disease.
Non-invasive—A procedure that does not penetrate the body.
Radioactive isotope—One of two or more atoms
with the same number of protons but a different
number of neutrons with a nuclear composition.
In nuclear scanning, radioactive isotopes are used
as a diagnostic agent.
Technetium—A radioactive isotope frequently used
in radionuclide scanning of the heart and other
organs. It is produced during nuclear fission reactions.
Ventricles—The heart’s lower chambers are called
the left and right ventricles. They send blood to the
lungs and throughout the body. The MUGA scan is
performed to evaluate the ventricles.

Texas Heart Institute. Heart Information Service. P.O. Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto

Multiple chemical sensitivity
Definition
Multiple chemical sensitivity—also known as
MCS syndrome, environmental illness, idiopathic
environmental intolerance, chemical AIDS, total
2489

Multiple chemical sensitivity

The MUGA scan is usually performed in a hospital’s nuclear medicine department, but it can also be
performed in an outpatient facility or at the patient’s
bedside if equipment is available. The scan is done
immediately after injection of the technetium and
usually takes about 30 minutes to one hour. It is also
called multigated graft acquisition, multigated acquisition scan, cardiac blood-pool imaging, and equilibrium radionuclide angiography. Test results can be
affected by patient movement during the test, electrocardiogram abnormalities, an irregular heartbeat, or
long-acting nitrates.

Multiple chemical sensitivity

allergy syndrome, or simply MCS—is a disorder in
which a person develops symptoms from exposure to
chemicals in the environment. With each incidence of
exposure, lower levels of the chemical will trigger a
reaction and the person becomes increasingly vulnerable to reactions triggered by other chemicals.
Medical experts disagree on the cause of the syndrome, and as to whether MCS is a clinically recognized illness. In a 1992 position statement that
remained unchanged as of early 2000, the American
Medical Association’s Council on Scientific Affairs
did not recognize MCS as a clinical condition due to
a lack of accepted diagnostic criteria and controlled
studies on the disorder. A more recent discussion of
methodological problems in published studies of
MCS, as well as recommendations for patient care,
may be found in the 1999 position paper on MCS
drafted by the American College of Occupational
and Environmental Medicine (ACOEM). As of 2003,
however, many researchers in Europe as well as the
United States regard MCS as a contemporary version
of neurasthenia, a concept first introduced by a physician named George Miller Beard in 1869.

Description
Multiple chemical sensitivity typically begins with
one high-dose exposure to a chemical, but it may also
develop with long-term exposure to a low level of a
chemical. Chemicals most often connected with MCS
include: formaldehyde; pesticides; solvents; petrochemical fuels such as diesel, gasoline, and kerosene;
waxes, detergents, and cleaning products; latex;
tobacco smoke; perfumes and fragrances; and artificial colors, flavors, and preservatives. People who
develop MCS are commonly exposed in one of the
following situations: on the job as an industrial
worker; residing or working in a poorly ventilated
building; or living in conditions of high air or water
pollution. Others may be exposed in unique incidents.
Because MCS is difficult to diagnose, estimates vary
as to what percentage of the population develops MCS.
However, most MCS patients are female. The median
age of MCS patients is 40 years old, and most experienced symptoms before they were 30 years old. There is
also a large percentage of Persian Gulf War veterans
who have reported symptoms of chemical sensitivity
since their return from the Gulf in the early 1990s.

Causes and symptoms
Chemical exposure is often a result of indoor air
pollution. Buildings that are tightly sealed for energy
2490

conservation may cause a related illness called sick
building syndrome, in which people develop symptoms from chronic exposure to airborne environmental chemicals such as formaldehyde from the furniture,
carpet glues, and latex caulking. A person moving into
a newly constructed building, which has not had time
to degas, may experience the initial high-dose exposure that leads to MCS.
As of late 2002, the specific biochemical and physiological mechanisms in humans that lead to MCS are
not well understood. A recent hypothesis, however,
suggests that MCS is the end result of four different
mechanisms of sensitization acting to reinforce one
another. Further research is required to test this
hypothesis.
The symptoms of MCS vary from person to person
and are not chemical-specific. Symptoms are not limited
to one physiological system, but primarily affect the
respiratory and nervous systems. Symptoms commonly
reported are headache, fatigue, weakness, difficulty concentrating, short-term memory loss, dizziness, irritability and depression, itching, numbness, burning
sensation, congestion, sore throat, hoarseness, shortness
of breath, cough, and stomach pains.
One commonly reported symptom of MCS is a
heightened sensitivity to odors, including a stronger
emotional reaction to them. A Japanese study published in late 2002 reported that patients diagnosed
with MCS can identify common odors as accurately
as most people, but regard a greater number of them as
unpleasant.
One test that has been devised to evaluate patients
with MCS is the capsaicin inhalation test. Capsaicin is
an alkaloid found in hot peppers that is sometimes
used in topical creams and rubs for the treatment of
arthritis. When inhaled, capsaicin causes coughing in
healthy persons as well as those with allergies that
affect the airway; however, persons with MCS cough
more deeply and frequently than control subjects
when given a dose of capsaicin. Although the test is
not diagnostic in the strict sense, it has been shown to
be an effective way of identifying patients with MCS.

Diagnosis
Multiple chemical sensitivity is a twentieth-century disorder, becoming more prevalent as more
human-made chemicals are introduced into the environment in greater quantities. It is especially difficult to
diagnose because it presents no consistent or measurable set of symptoms and has no single diagnostic test
or marker. For example, a 2002 study of PET scans of
GALE ENCYCLOPEDIA OF MEDICINE

Some MCS patients may be helped by a psychologic evaluation, particularly if they show signs of
panic attacks or other anxiety disorders. It is known
that many patients with MCS suffer from comorbid
depression and anxiety. In addition, MCS patients
appear to have high rates of mood disorders compared
to asthma patients as well as normal test subjects.

Treatment
While doctors may recommend antihistamines,
analgesics, and other medications to combat the symptoms, the most effective treatment is to avoid those
chemicals which trigger the symptoms. This becomes
increasingly difficult as the number of offending chemicals increases, and people with MCS often remain at
home where they are able to control the chemicals in
their environment. This isolation often limits their
abilities to work and socialize, so supportive counseling may also be appropriate.

Alternative treatment
Some MCS patients find relief with detoxification
programs of exercise and sweating, and chelation of
heavy metals. Others support their health with nutritional regimens and immunotherapy vaccines. Some
undergo food-allergy testing and testing for accumulated pesticides in the body to learn more about their
condition and what chemicals to avoid. Homeopathy
and acupuncture can give added support to any treatment program for MCS patients. Botanical medicine
can help to support the liver and other involved organs.

Prognosis
Once MCS sets in, sensitivity continues to increase
and a person’s health continues to deteriorate. Strictly
avoiding exposure to triggering chemicals for a year or
more may improve health.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Capsaicin—An alkaloid found in hot peppers that is
used in an inhalation test to identify patients with MCS.
Degas—To release and vent gases. New building
materials often give off gases and odors and the air
should be well circulated to remove them.
Neurasthenia—A term coined in the late nineteenth century to refer to a condition of chronic
mental and physical weakness and fatigue. Some
researchers regard MCS as a twentieth-century version of neurasthenia.
Sick building syndrome—An illness related to MCS
in which a person develops symptoms in response
to chronic exposure to airborne environmental
chemicals found in a tightly sealed building.

Prevention
Multiple chemical sensitivity is difficult to prevent
because even at high-dose exposures, different people
react differently. Ensuring adequate ventilation in
situations with potential for acute high-dose or
chronic low-dose chemical exposure, as well as wearing the proper protective equipment in industrial
situations, will minimize the risk.
Resources
BOOKS

American Psychiatric Association.Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised. Washington,
DC: American Psychiatric Association, 2000.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Multiple Chemical Sensitivity Syndrome.’’ Section 21,
Chapter 287. In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Gibson, Pamela. Multiple Chemical Sensitivity: A Survival
Guide. Oakland, CA: New Harbinger Publications, 2000.
PERIODICALS

Bornschein, S., C. Hausteiner, A. Drzezga, et al. ‘‘PET in
Patients With Clear-Cut Multiple Chemical
Sensitivity (MCS).’’ Nuklearmedizin 41 (December
2002): 233–239.
Bornschein, S., C. Hausteiner, T. Zilker, and H. Forstl.
‘‘Psychiatric and Somatic Disorders and Multiple
Chemical Sensitivity (MCS) in 264 ‘Environmental
Patients’.’’ Psychological Medicine 32 (November
2002): 1387–1394.
Caccappollo-vanVliet, E., K. Kelly-McNeil, B. Natelson,
et al. ‘‘Anxiety Sensitivity and Depression in Multiple
Chemical Sensitivities and Asthma.’’ Journal of
2491

Multiple chemical sensitivity

MCS patients found no significant functional changes
in the patients’ brain tissues. Physicians are often
either unaware of MCS as a condition, or refuse to
accept that MCS exists. They may be unable to diagnose it, or may misdiagnose it as another degenerative
disease, or may label it as a psychosomatic illness (a
physical illness that is caused by emotional problems).
Their lack of understanding generates frustration,
anxiety, and distrust in patients already struggling
with MCS. However, a new specialty of medicine is
evolving to address MCS and related illnesses: occupational and environmental medicine. A physician
looking for MCS will take a complete patient history
and try to identify chemical exposures.

Multiple endocrine neoplasia syndromes

Occupational and Environmental Medicine 44 (October
2002): 890–901.
Johansson, A., O. Lowhagen, E. Millqvist, and M. Bende.
‘‘Capsaicin Inhalation Test for Identification of
Sensory Hyperreactivity.’’ Respiratory Medicine 96
(September 2002): 731–735.
Ojima, M., H. Tonori, T. Sato, et al. ‘‘Odor Perception in
Patients with Multiple Chemical Sensitivity.’’ Tohoku
Journal of Experimental Medicine 198 (November
2002): 163–173.
Pall, M. L. ‘‘NMDA Sensitization and Stimulation by
Peroxynitrite, Nitric Oxide, and Organic Solvents as the
Mechanism of Chemical Sensitivity in Multiple
Chemical Sensitivity.’’ FASEB Journal 16 (September
2002): 1407–1417.
Schafer, M. L. ‘‘On the History of the Concept Neurasthenia
and Its Modern Variants Chronic-Fatigue-Syndrome,
Fibromyalgia and Multiple Chemical Sensitivities’’ [in
German] Fortschritte der Neurologie-Psychiatrie 70
(November 2002): 570–582.
Ternesten-Hasseus, E., M. Bende, and E. Millqvist.
‘‘Increased Capsaicin Cough Sensitivity in Patients with
Multiple Chemical Sensitivity.’’ Journal of Occupational
and Environmental Medicine 44 (November 2002):
1012–1017.
ORGANIZATIONS

American Academy of Environmental Medicine. P.O. Box
CN 1001-8001, New Hope, PA 18938. (215) 862-4544.
American College of Occupational and Environmental
Medicine (ACOEM). 1114 North Arlington Heights
Road, Arlington Heights, IL 60004. (847) 818-1800.
<www.acoem.org>.
OTHER

‘‘Multiple Chemical Sensitivities: Idiopathic Environmental
Intolerance.’’ Position Statement by the American
College of Occupational and Environmental Medicine
(ACOEM), April 26, 1999. <www.acoem.org/
position/statements.asp?CATA_ID=46>.

Bethany Thivierge
Rebecca J. Frey, PhD

Multiple endocrine adenomatosis see
Multiple endocrine neoplasia syndromes

Multiple endocrine neoplasia
syndromes
Definition
The multiple endocrine neoplasia (MEN) syndromes are three related disorders affecting the thyroid and other hormonal (endocrine) glands of the
2492

body. MEN has previously been known as familial
endocrine adenomatosis.

Description
The three forms of MEN are MEN1 (Wermer’s
syndrome), MEN2A (Sipple syndrome), and MEN2B
(previously known as MEN3). Each is an autosomal
dominant genetic condition which predisposes to
hyperplasia (excessive growth of cells) and tumor formation in a number of endocrine glands.

Causes and symptoms
MEN1 patients experience hyperplasia or tumors
of several endocrine glands, including the parathyroids,
the pancreas, and the pituitary. The most frequent
symptom of MEN1 is hyperparathyroidism.
Overgrowth of the parathyroid glands leads to over
secretion of parathyroid hormone, which leads to elevated blood calcium levels, kidney stones, weakened
bones, and nervous system depression. Almost all
MEN1 patients show parathyroid symptoms by age 40.
Tumors of the pancreas known as gastrinomas are
also common in MEN1. Excessive secretion of gastrin
(a hormone secreted into the stomach to aid in digestion) by these tumors can cause upper gastrointestinal
ulcers. The anterior pituitary and the adrenal glands
can also be affected. Unlike MEN2, the thyroid gland
is rarely involved in MEN1 symptoms.
Patients with MEN2A and MEN2B experience
two main symptoms, medullary thyroid cancer
(MTC) and a tumor of the adrenal gland medulla
known as pheochromocytoma. MTC is a slow-growing
cancer, but one that can be cured in less than 50% of
cases. Pheochromocytoma is usually a benign tumor
that causes excessive secretion of adrenal hormones,
which, in turn, can cause life-threatening hypertension
and cardiac arrhythmia.
The two forms of MEN2 are distinguished by
additional symptoms. MEN2A patients have a predisposition to increase in size (hypertrophy) and to
develop tumors of the parathyroid gland. Although
similar to MEN1, less than 20% of MEN2A patients
will show parathyroid involvement.
MEN2B patients show a variety of additional
conditions: a characteristic facial appearance with
swollen lips; tumors of the mucous membranes of the
eye, mouth, tongue, and nasal cavity; enlarged colon;
and skeletal abnormalities. Symptoms develop early in
life (often under five years of age) in cases of MEN2B
and the tumors are more aggressive. MEN2B is about
ten-fold less common than MEN2A.
GALE ENCYCLOPEDIA OF MEDICINE

C.

B.

D.

F.

Both types of MEN2 are caused by mutations in
another gene, known as RET. A mutation in only one
copy of the RET gene is sufficient to cause disease. A
number of different mutations can lead to MEN2A,
but only one specific genetic alteration leads to
MEN2B.
For all types of MEN, the children of an affected
individual have a 50% chance of inheriting the defective gene.

E.
G.

Diagnosis

H.

I.

J.

Classical diagnosis of MEN is based on clinical
features and on testing for elevated hormone levels.
For MEN1, the relevant hormone is parathyroid hormone. For both types of MEN2, the greatest concern
is development of medullary thyroid cancer. MTC can
be detected by measuring levels of the thyroid hormone, calcitonin. Numerous other hormone levels
can be measured to assess the involvement of the
various other endocrine glands.
Diagnosis of MEN2B can be made by physical
examination alone. However, MEN2A shows no distinct physical features and must be identified by measuring hormone levels or by finding endocrine tumors.
Since 1994, genetic screening using DNA technology has been available for both MEN1 and MEN2.
This new methodology allows diagnosis prior to the
onset of symptoms.
In the past, there was no way of definitively identifying which children had inherited the defective gene.
As a result, all children had to be considered at risk. In
the case of MEN2A and MEN2B, children would
undergo frequent calcitonin testing. Molecular techniques now allow a positive distinction to be made
between children who are and are not actually at risk.

The human endocrine system: A. Hypothalamus. B. Pineal. C.
Pituitary. D. Parathyroid. E. Thymus. F. Thyroid. G. Adrenals.
H. Pancreas. I. Ovaries (female). J. Testes (male). (Illustration by
Electronic Illustrators Group.)

Children who are identified as carriers of the RET
gene can be offered total thyroidectomy on a preventative
(prophylactic) basis to prevent the development of MTC.

Treatment
MEN1 is caused by mutation at the PYGM gene.
PYGM is one of a group of genes known as tumor
suppressor genes. A patient who inherits one defective
copy of a tumor suppressor gene from either parent
has a strong predisposition to the disease because of
the high probability of incurring a second mutation in
at least one dividing cell. That cell no longer possesses
GALE ENCYCLOPEDIA OF MEDICINE

No comprehensive treatment is available for
genetic conditions such as MEN. However, some of
the consequences of MEN can be symptomatically
treated.
Pheochromocytoma in both types of MEN 2 can
be cured by surgical removal of this slow growing
tumor.
2493

Multiple endocrine neoplasia syndromes

A.

even one normal copy of the gene. When both copies
are defective, tumor suppression fails and tumors
develop.

Multiple myeloma

KEY TERMS
Endocrine—A term used to describe the glands that
produce hormones in the body.
Hyperplasia—An overgrowth of normal cells
within an organ or tissue.
Medullary thyroid cancer (MTC)—A slow-growing
tumor associated with MEN.
Neoplasm—An abnormal formation of tissue; for
example, a tumor.
Pheochromocytoma—A tumor of the medullary of
the adrenal gland.

Treatment of MTC is by surgical removal of the
thyroid, although doctors may disagree at what stage
to remove the thyroid. After thyroidectomy, the
patient will receive normal levels of thyroid hormone
orally or by injection.
Even when surgery is performed early, metastatic
spread of the cancer may have already occurred. Since
this cancer is slow growing, metastasis may not be
obvious. Metastasis is very serious in MTC because
chemotherapy and radiation therapy are not effective in
controlling its spread.

Prognosis
Diagnosed early, the prognosis for the MEN diseases is reasonably good, even for MEN2B, the most
dangerous of the three forms. Even in the absence of
treatment, a few individuals with MEN2A mutations
will never show any symptoms at all. Analysis of atrisk family members using molecular genetic techniques will lead to earlier treatment and improved
outcomes.

Prevention
One of the most serious consequences of MEN is
MTC, which can be prevented by thyroidectomy.
There is no preventive measure to block the occurrence of genetic mutations such as those that cause
MEN.

Multiple myeloma
Definition
Multiple myeloma is a cancer in which antibodyproducing plasma cells grow in an uncontrolled and
invasive (malignant) manner.

Description
Multiple myeloma, also known as plasma cell
myeloma, is the second-most common cancer of the
blood. It is the most common type of plasma cell
neoplasm. Multiple myeloma accounts for approximately 1% of all cancers and 2% of all deaths from
cancer. Multiple myeloma is a disease in which malignant plasma cells spread through the bone marrow
and hard outer portions of the large bones of the
body. These myeloma cells may form tumors called
plasmacytomas. Eventually, multiple soft spots or
holes, called osteolytic lesions, form in the bones.
Bone marrow is the spongy tissue within the
bones. The breastbone, spine, ribs, skull, pelvic
bones, and the long bone of the thigh all are particularly rich in marrow. Bone marrow is a very active
tissue that is responsible for producing the cells that
circulate in the blood. These include the red blood cells
that carry oxygen, the white blood cells that develop
into immune system cells, and platelets, which cause
blood to clot.
Plasma cells and immunoglobulins
Plasma cells develop from B-lymphocytes or
B-cells, a type of white blood cell. B-cells, like all
blood cells, develop from unspecialized stem cells in
the bone marrow. Each B-cell carries a specific antibody that recognizes a specific foreign substance called
an antigen. Antibodies are large proteins called immunoglobulins (Igs), which recognize and destroy foreign
substances and organisms such as bacteria. When a Bcell encounters its antigen, it begins to divide rapidly to
form mature plasma cells. These plasma cells are all
identical (monoclonal). They produce large amounts of
identical antibody that are specific for the antigen.
Malignant plasma cells

Resources
ORGANIZATIONS

Canadian MEN Society. P.O. Box 100, Meola,
Saskatchewan SOM 1XO. (306) 892-2080.

Victor Leipzig, PhD
2494

Multiple myeloma begins when the genetic material (DNA) is damaged during the development of a
stem cell into a B-cell in the bone marrow. This causes
the cell to develop into an abnormal or malignant
plasmablast, a developmentally early form of plasma
cell. Plasmablasts produce adhesive molecules that
GALE ENCYCLOPEDIA OF MEDICINE

In most cases of multiple myeloma, the malignant
plasma cells all make an identical Ig. Igs are made up
of four protein chains that are bonded together. Two
of the chains are light and two are heavy. There are
five classes of heavy chains, corresponding to five
types of Igs with different immune system functions.
The Igs from myeloma cells are nonfunctional and are
called paraproteins. All of the paraproteins from any
one individual are monoclonal (identical) because the
myeloma cells are identical clones of a single plasma
cell. Thus, the paraprotein is a monoclonal protein or
M-protein. The M-proteins crowd out the functional
Igs and other components of the immune system. They
also cause functional antibodies, which are produced
by normal plasma cells, to rapidly break down. Thus,
multiple myeloma depresses the immune system.
In about 75% of multiple myeloma cases, the
malignant plasma cells also produce monoclonal
light chains, or incomplete Igs. These are called
Bence-Jones proteins and are secreted in the urine.
Approximately 1% of multiple myelomas are called
nonsecretors because they do not produce any abnormal Ig.
Osteolytic lesions
About 70% of individuals with multiple myeloma
have soft spots or lesions in their bones. These lesions
can vary from quite small to grapefruit-size. In part,
these lesions occur because the malignant plasma cells
rapidly outgrow the normal bone-forming cells. In
addition, malignant myeloma cells produce factors
that affect cells called osteoclasts. These are the cells
that normally destroy old bone, so that new bone can
be produced by cells called osteoblasts. The myeloma
cell factors increase both the activation and the growth
of osteoclasts. As the osteoclasts multiply and migrate,
they destroy healthy bone and create lesions.
Osteoporosis, or widespread bone weakness, may
develop.
There are more than 40,000 multiple myeloma
patients in the United States. The American Cancer
Society predicts an additional 14,400 new cases in
2001. About 11,200 Americans will die of the disease
in 2001. Multiple myeloma is one of the leading causes
of cancer deaths among African Americans.
GALE ENCYCLOPEDIA OF MEDICINE

In Western industrialized countries, approximately four people in 100,000 develop multiple myeloma. The incidence of multiple myeloma among
African Americans is 9.5 per 100,000, about twice
that of Caucasians. Asians have a much lower incidence of the disease. In China, for example, the incidence of multiple myeloma is only one in 100,000. The
offspring and siblings of individuals with multiple
myeloma are at a slightly increased risk for the disease.
At diagnosis, the average age of a multiple myeloma patient is 68 to 70. Although the average age at
onset is decreasing, most multiple myelomas still occur
in people over 40. This cancer is somewhat more prevalent in men than in women.

Causes and symptoms
Associations
The cause of multiple myeloma has not been
determined. However, a number of possible associations have been identified:


decreased immune system function; the immune systems of older individuals may be less efficient at
detecting and destroying cancer cells



genetic (hereditary) factors, suggested by the
increased incidence in some ethnic groups and
among family members



occupational factors, suggested by the increased incidence among agricultural, petroleum, wood, and
leather workers, and cosmetologists



long-term exposure to herbicides, pesticides, petroleum products, heavy metals, plastics, and dusts such
as asbestos



radiation exposure, as among Japanese atomic bomb
survivors, nuclear weapons workers, and medical
personnel such as radiologists



Kaposi’s sarcoma-associated herpes virus (also
called human herpes virus-8 or HHV-8), found in
the blood and bone marrow cells of many multiple
myeloma patients
Early symptoms

The accumulation of malignant plasma cells can
result in tiny cracks or fractures in bones. Malignant
plasma cells in the bone marrow can suppress the
formation of red and white blood cells and platelets.
About 80% of individuals with multiple myeloma are
anemic due to low red blood cell formation. Low white
blood cell formation results in increased susceptibility
to infection, since new, functional antibodies are not
2495

Multiple myeloma

allow them to bond to the inside of the bone marrow.
A growth factor, called interleukin-6, promotes
uncontrolled growth of these myeloma cells in the
bone marrow and prevents their natural death.
Whereas normal bone marrow contains less than 5%
plasma cells, bone marrow of an individual with multiple myeloma contains over 10% plasma cells.

Multiple myeloma

produced. In addition, normal circulating antibodies
are rapidly destroyed. Low platelet formation can
result in poor blood clotting. It is rare, however, that
insufficient white blood cell and platelet formations
are presenting signs of multiple myeloma.
These factors cause the early symptoms of multiple myeloma:


pain in the lower back or ribs



fatigue and paleness due to anemia (low red blood
cell count)





frequent and recurring infections, including bacterial
pneumonia, urinary-tract and kidney infections, and
shingles

Serum proteins
The accumulation of M-proteins in the serum (the
liquid portion of the blood) may cause additional
complications, such as hyperviscosity syndrome, or
thickening of the blood (though rare in multiple myeloma patients). Symptoms of hyperviscosity include:


fatigue



headaches



shortness of breath



mental confusion



chest pain



kidney damage and failure



vision problems



Raynaud’s phenomenon

bleeding
Bone destruction

Bone pain, particularly in the backbone, hips, and
skull, is often the first symptom of multiple myeloma.
As malignant plasma cells increase in the bone marrow, replacing normal marrow, they exert pressure on
the bone. As overly-active osteoclasts (large cells
responsible for the breakdown of bone) remove bone
tissue, the bone becomes soft. Fracture and spinal cord
compression may occur.

Poor blood circulation, or Raynaud’s phenomenon, can affect any part of the body, but particularly
the fingers, toes, nose, and ears.

Plasmacytomas (malignant tumors of plasma
cells) may weaken bones, causing fractures.
Fractured bones or weak or collapsed spinal bones,
in turn, may place unusual pressure on nearby nerves,
resulting in nerve pain, burning, or numbness and
muscle weakness. Proteins produced by myeloma
cells also may damage nerves.

Amyloidosis is a rare complication of multiple
myeloma. It usually occurs in individuals whose
plasma cells produce only Ig light chains. These
Bence-Jones proteins combine with other serum proteins to form amyloid protein. This starchy substance
can invade tissues, organs, and blood vessels. In particular, amyloid proteins can accumulate in the kidneys,
where they block the tiny tubules that are the kidney’s
filtering system. Indicators of amyloidosis include:

Calcium from the destroyed bone enters the blood
and urine, causing hypercalcemia, a medical condition
in which abnormally high concentrations of calcium
compounds exist in the bloodstream. High calcium
affects nerve cell and kidney function. The symptoms
of hypercalcemia include:

Cryoglobulinemia occurs when the protein in the
blood forms particles under cold conditions. These
particles can block small blood vessels and cause
pain and numbness in the toes, fingers, and other
extremities during cold weather.



carpal tunnel syndrome



kidney failure



liver failure



heart failure



weakness and fatigue



depression



mental confusion

Diagnosis



constipation

Blood and urine tests



increased thirst



icreased urination



nausea and vomiting



kidney pain



kidney failure

Hypercalcemia affects about one-third of multiple
myeloma patients.
2496

Often, the original diagnosis of multiple myeloma
is made from routine blood tests that are performed
for other reasons. Blood tests may indicate:


anemia



abnormal red blood cells



high serum protein levels



how levels of normal antibody
GALE ENCYCLOPEDIA OF MEDICINE

high calcium levels



high blood urea nitrogen (BUN) levels



high creatinine levels

Multiple myeloma



Urea and creatinine normally are excreted in the
urine. High levels of urea and creatinine in the blood
indicate that the kidneys are not functioning properly
to eliminate these substances.
Protein electrophoresis is a laboratory technique
that uses an electrical current to separate the different
proteins in the blood and urine on the basis of size and
charge. Since all of the multiple myeloma M-proteins
in the blood and urine are identical, electrophoresis of
blood and urine from a patient with multiple myeloma
shows a large M-protein spike, corresponding to the
high concentration of monoclonal Ig. Electrophoresis
of the urine also can detect Bence-Jones proteins.
Bones
A bone marrow aspiration utilizes a very thin, long
needle to remove a sample of marrow from the hip
bone. Alternatively, a bone marrow biopsy with a larger needle removes solid marrow tissue. The marrow is
examined under the microscope for plasma cells and
tumors. If 10% to 30% of the cells are plasma cells,
multiple myeloma is the usual diagnosis.
X rays are used to detect osteoporosis, osteolytic
lesions, and fractures. Computer-assisted tomography
(CAT or CT) scans can detect lesions in both bone and
soft tissue. Magnetic resonance imaging (MRI) may
give a more detailed image of a certain bone or a
region of the body.

This x ray of the patient’s left clavicle indicates an occurrence
of myelomas in the bone. (Custom Medical Stock Photo.
Reproduced by permission.)

Clinical stages
The Durie-Salmon system is used to stage multiple myeloma. Stage I multiple myeloma requires all of
the following (1 gram = approx. 0.02 pints, 1 deciliter
= approx. 0.33 ounces):


hemoglobin (the oxygen-transporting molecule of
red blood cells) above 10 grams/deciliter (g/dl)



serum calcium below 12 mg/dl



normal bone
plasmacytoma



low M-protein, based on established guideline levels
of Ig protein chains

Treatment
Related disorders
Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in which a
monoclonal Ig is detectable. However, there are no
tumors or other symptoms of multiple myeloma.
MGUS occurs in about 1% of the general population
and in about 3% of those over age 70. Over a period of
years, about 16% to 20% of those with MGUS will
develop multiple myeloma or a related cancer called
malignant lymphoma.
Occasionally, only a single plasmacytoma develops, either in the bone marrow (isolated plasmacytoma of the bone) or other tissues or organs
(extramedullary plasmacytoma). Some individuals
with solitary plasmacytoma may develop multiple
myeloma.
GALE ENCYCLOPEDIA OF MEDICINE

structure

or

only

isolated

Approximately 5% of multiple myeloma cases are
not progressing at diagnosis, and may not progress for
months or years. This is called smoldering myeloma.
These patients have stage I blood chemistry but no
symptoms.
Stage II multiple myeloma fits neither stage I nor
stage III. Stage III multiple myeloma meets one or
more the following criteria:


hemoglobin below 8.5 g/dl



serum calcium above 12 mg/dl



advanced bone lesions



high M-protein
2497

Multiple myeloma

Each stage is subclassified as A or B, based on
serum creatinine indicators of normal or abnormal
kidney function. Most patients have stage III multiple
myeloma at diagnosis.
Prognostic indicators
Prognostic indicators for multiple myeloma may
be used instead of, or in addition to, the staging system
described above. Prognostic indicators are laboratory
tests that help to define the stage of the disease at
diagnosis, and its progression during treatment.
These indicators are:


plasmablastic multiple myeloma (presence of plasmablasts, the precursor malignant plasma cells)



plasma cell labeling index (the percentage of plasma
cells that are actively dividing)



beta 2-microglobulin, a protein secreted by B-cells
that correlates with the myeloma cell mass (also indicates kidney damage)

Since multiple myeloma often progresses slowly,
and since the treatments can be toxic, the disease may
not be treated until M-protein levels in the blood are
quite high. In particular, MGUS and smoldering myeloma may be followed closely but not treated. Solitary
plasmacytomas are treated with radiation and/or surgery and followed closely with examinations and
laboratory tests.
Chemotherapy
Chemotherapy, or treatment with anti-cancer
drugs, is used for multiple myeloma. MP, a combination of the drugs melphalan and prednisone, is the
standard treatment. Usually, the drugs are taken by
mouth every 3 to 4 weeks for 6 to 9 months or longer,
until the M-protein levels in the blood stop decreasing.
MP usually results in a 50% reduction in M-protein.
Dexamethasone, a corticosteroid, sometimes is
used to treat the elderly or those in poor health. It
can drop the M-protein levels by 40% in untreated
individuals and by 20% to 40% in patients who have
not responded to previous treatment. Other chemotherapy drugs, including cyclophosphamide, carmustine, doxorubicin, vincristine, and chlorambucil,
may be used as well.
Multiple myeloma usually recurs within a year
after the end of chemotherapy. Although the chemotherapy can be repeated after each recurrence, it is
progressively less responsive to treatment.
Side effects of chemotherapy may include:


anemia

2498



hair loss



nausea



vomiting



diarrhea



mood swings



swelling



acne

These side effects disappear after treatment is
discontinued.
Other drug treatments
Bisphosphonates are drugs that inhibit the activity of osteoclasts. These drugs can slow the progression of bone disease, reduce pain, and help prevent
bone fractures. Different types of bisphosphonates
inhibit osteoclasts in different ways. They also reduce
the production of interleukin-6 by bone marrow cells.
Laboratory studies suggest that bisphosphonates may
kill or inhibit the growth of multiple myeloma cells.
Pamidronate is the most common bisphosphonate for
treating multiple myeloma.
The drug thalidomide appears to have several
anti-myeloma activities. Thalidomide affects the
immune system in various ways and it appears to
inhibit myeloma cells, both directly and indirectly. It
also inhibits the growth of new blood vessels that are
needed by tumors. However, if thalidomide is taken
during pregnancy, it an cause severe birth defects or
death of the fetus.
The drug allopurinol may be used to reduce high
blood levels of uric acid that result from kidney dysfunction. Diuretics can improve kidney function.
Infections require prompt treatment with antibiotics.
BONE AND PERIPHERAL BLOOD STEM CELL
TRANSPLANTATION. Bone marrow or peripheral

blood stem cell transplantations (PBSCT) are used to
replace the stem cells of the bone marrow following
high-dosage chemotherapy. Chemotherapy destroys
the bone marrow stem cells that are necessary to produce new blood cells. In an autologous transplant, the
patient’s bone marrow stem cells or peripheral blood
stem cells (immature bone marrow cells found in the
blood) are collected, treated with drugs to kill any
myeloma cells, and frozen prior to chemotherapy.
Growth factors are used to increase the number of
peripheral stem cells prior to collection. A procedure
called apheresis is used to collect the peripheral stem
cells. Following high-dosage chemotherapy, the stem
cells are reinjected into the individual. In an allogeneic
GALE ENCYCLOPEDIA OF MEDICINE

Amyloidosis—A complication of multiple myeloma
in which amyloid protein accumulates in the kidneys
and other organs, tissues, and blood vessels.
Anemia—Any condition in which the red blood cell
count is below normal.
Antibody—Immunoglobulin produced by immune
system cells that recognizes and binds to a specific
foreign substance (antigen).
Antigen—Foreign substance that is recognized by a
specific antibody.
B-cell (B-lymphocyte)—Type of white blood cell
that produces antibodies.
Bence-Jones protein—Light chain of an immunoglobulin that is overproduced in multiple myeloma and
is excreted in the urine.
Beta 2-microglobulin—Protein produced by B-cells;
high concentrations in the blood are indicative of
multiple myeloma.

Immunoglobulin (Ig)—Antibody; large protein produced by B-cells that recognizes and binds to a
specific antigen.
M-protein—Monoclonal or myeloma protein; paraprotein; abnormal antibody found in large amounts
in the blood and urine of individuals with multiple
myeloma.
Malignant—A characteristic of cancer cells that
grow uncontrollably and invade other tissues.
Monoclonal—Identical cells or proteins; cells
(clones) derived from a single, genetically-distinct
cell, or proteins produced by these cells.
Monoclonal gammopathy of undetermined significance (MGUS)—Common condition in which Mprotein is present, but there are no tumors or other
symptoms of disease.
Neoplasm—Tumor made up of cancer cells.
Osteoblast—Bone-forming cell.

Cryoglobulinemia—Condition in which protein in the
blood forms particles in the cold, blocking blood vessels, leading to pain and numbness of the extremities.

Osteoclast—Cell that absorbs bone.
Osteolytic lesion—Soft spot or hole in bone caused
by cancer cells.

Electrophoresis—Use of an electrical field to separate
proteins in a mixture (such as blood or urine), on the
basis of the size and electrical charge of the proteins.
Hemoglobin—Protein in red blood cells that carries
oxygen.

Osteoporosis—Condition in which the bones
become weak and porous, due to loss of calcium
and destruction of cells.
Paraprotein—M-protein; abnormal immunoglobulin produced in multiple myeloma.

Hypercalcemia—Abnormally high levels of calcium
in the blood.

Plasma cell—Type of white blood cell that produces
antibodies; derived from an antigen-specific B-cell.

Hyperviscosity—Thick, viscous blood, caused by
the accumulation of large proteins, such as immunoglobulins, in the serum.

Platelet—Cell that is involved in blood clotting.

transplant, the donor stem cells come from a genetically-related individual such as a sibling.

transfused back into the patient, along with a plasma
substitute or donated plasma.

Other treatments
Blood transfusions may be required to treat severe
anemia.
Plasmapheresis, or plasma exchange transfusion,
may be used to thin the blood to treat hyperviscosity
syndrome. In this treatment, blood is removed and
passed through a machine that separates the plasma,
containing the M-protein, from the red and white
blood cells and platelets. The blood cells are
GALE ENCYCLOPEDIA OF MEDICINE

Stem cell—Undifferentiated cell that retains the ability to develop into any one of numerous cell types.

Multiple myeloma may be treated with highenergy x rays directed at a specific region of the
body. Radiation therapy is used for treating bone pain.
Alternative treatment
Interferon alpha, an immune-defense protein that is
produced by some white blood cells and bone marrow
cells, can slow the growth of myeloma cells. It usually is
given to patients following chemotherapy, to prolong
their remission. However, interferon may have toxic
effects in older individuals with multiple myeloma.
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Multiple myeloma

KEY TERMS

Multiple personality disorder

Once multiple myeloma is in remission, calcium
and vitamin D supplements can improve bone density.
It is important not to take these supplements when the
myeloma is active. Individuals with multiple myeloma
must drink large amounts of fluid to counter the
effects of hyperviscous blood.
Prognosis
The prognosis for individuals with MGUS or solitary plasmacytoma is very good. Most do not develop
multiple myeloma. However, approximately 15% of all
patients with multiple myeloma die within three months
of diagnosis. About 60% respond to treatment and live
for an average of two and a half to three years following
diagnosis. Approximately 23% of patients die of other
illnesses associated with advanced age.
The prognosis for a given individual may be based
on the prognostic indicators described above. The
median survival for those without plasmablasts, and
with a low plasma cell labeling index (PCLI) and low
beta 2-microglobulin, is 5.5 years. The median survival
for patients with plasmablastic multiple myeloma, or
with a high PCLI (1% or greater) and high beta
2-microglobulin (4 or higher), is 1.9 and 2.4 years,
respectively. Many multiple myeloma patients are
missing part or all of chromosome 13. The deletion
of this chromosome, along with high beta 2-microglobulin, leads to a poor prognosis.
With treatment, multiple myeloma may go into
complete remission. This is defined as:


M-protein absent from the blood and urine



myeloma cells not detectable in the bone marrow



no clinical symptoms



negative laboratory tests

However, with very sensitive testing, a few myeloma cells are usually detectable and eventually lead to
a recurrence of the disease, in the bone or elsewhere in
the body.

Prevention
There are no clearly-established risk factors for
multiple myeloma and it is possible that a combination
of factors interact to cause the disease. Thus, there is
no method for preventing multiple myeloma.
Resources
BOOKS

Holland, Jimmie C., and Sheldon Lewis. The Human Side of
Cancer: Living with Hope, Coping with Uncertainty.
New York: HarperCollins, 2000.
2500

ORGANIZATIONS

Multiple Myeloma Research Foundation. 11 Forest Street,
New Canaan, CT 06840. (203) 972-1250. <http://
www.multiplemyeloma.org>. Information and
research funding.
OTHER

‘‘About Myeloma.’’ Multiple Myeloma Research
Foundation. April 16, 2001. [cited June 15,2001].
<http://www.multiplemyeloma.org/
aboutmyeloma.html>.
Complementary and Alternative Therapies for Leukemia,
Lymphoma, Hodgkin’s Disease and Myeloma. The
Leukemia and Lymphoma Society. March 27, 2001.
[cited June 15, 2001]. <http://www.leukemialymphoma.org>.
Facts and Statistics About Leukemia, Lymphoma, Hodgkin’s
Disease and Myeloma. The Leukemia and Lymphoma
Society. March 15, 2001. [cited Mar27, 2001]. <http://
www.leukemia-lymphoma.org>.
‘‘Multiple Myeloma and Other Plasma Cell Neoplasms.’’
CancerNet National Cancer Institute. March 2001.
[cited April 16, 2001]. <http://cancernet.nci.nih.gov>.
‘‘Multiple Myeloma.’’ Cancer Resource Center. American
Cancer Society. April 16, 2001. [cited June 15, 2001].
<http://www3.cancer.org/cancerinfo>.

Margaret Alic, Ph.D.

Multiple personality disorder
Definition
Multiple personality disorder, or MPD, is a mental disturbance classified as one of the dissociative
disorders in the fourth edition of the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV). It
has been renamed dissociative identity disorder
(DID). MPD or DID is defined as a condition in
which ‘‘two or more distinct identities or personality
states’’ alternate in controlling the patient’s consciousness and behavior. Note: ‘‘Split personality’’ is not an
accurate term for DID and should not be used as a
synonym for schizophrenia.

Description
The precise nature of DID (MPD) as well as its
relationship to other mental disorders is still a subject
of debate. Some researchers think that DID may be a
relatively recent development in western society. It
may be a culture-specific syndrome found in western
society, caused primarily by both childhood abuse and
GALE ENCYCLOPEDIA OF MEDICINE

The most distinctive feature of DID is the formation and emergence of alternate personality states, or
‘‘alters.’’ Patients with DID experience their alters as
distinctive individuals possessing different names, histories, and personality traits. It is not unusual for DID
patients to have alters of different genders, sexual
orientations, ages, or nationalities. Some patients
have been reported with alters that are not even
human; alters have been animals, or even aliens from
outer space. The average DID patient has between two
and 10 alters, but some have been reported with over
one hundred.

Causes and symptoms
The severe dissociation that characterizes patients
with DID is currently understood to result from a set
of causes:


An innate ability to dissociate easily



Repeated episodes of severe physical or sexual abuse
in childhood



The lack of a supportive or comforting person to
counteract abusive relative(s)



The influence of other relatives with dissociative
symptoms or disorders

The relationship of dissociative disorders to childhood abuse has led to intense controversy and lawsuits
concerning the accuracy of childhood memories. The
brain’s storage, retrieval, and interpretation of childhood memories are still not fully understood.
GALE ENCYCLOPEDIA OF MEDICINE

The major dissociative symptoms experienced by
DID patients are amnesia, depersonalization, derealization, and identity disturbances.
Amnesia
Amnesia in DID is marked by gaps in the patient’s
memory for long periods of their past, in some cases,
their entire childhood. Most DID patients have amnesia, or ‘‘lose time,’’ for periods when another personality is ‘‘out.’’ They may report finding items in their
house that they can’t remember having purchased,
finding notes written in different handwriting, or
other evidence of unexplained activity.
Depersonalization
Depersonalization is a dissociative symptom in
which the patient feels that his or her body is unreal,
is changing, or is dissolving. Some DID patients
experience depersonalization as feeling to be outside
of their body, or as watching a movie of themselves.
Derealization
Derealization is a dissociative symptom in which
the patient perceives the external environment as
unreal. Patients may see walls, buildings, or other
objects as changing in shape, size, or color. DID
patients may fail to recognize relatives or close friends.
Identity disturbances
Identity disturbances in DID result from the
patient’s having split off entire personality traits or
characteristics as well as memories. When a stressful
or traumatic experience triggers the reemergence of
these dissociated parts, the patient switches—usually
within seconds—into an alternate personality. Some
patients have histories of erratic performance in
school or in their jobs caused by the emergence of
alternate personalities during examinations or other
stressful situations. Patients vary with regard to their
alters’ awareness of one another.

Diagnosis
The diagnosis of DID is complex and some physicians believe it is often missed, while others feel it is overdiagnosed. Patients have been known to have been
treated under a variety of other psychiatric diagnoses
for a long time before being re-diagnosed with DID.
The average DID patient is in the mental health care
system for six to seven years before being diagnosed as a
person with DID. Many DID patients are misdiagnosed
as depressed because the primary or ‘‘core’’ personality
2501

Multiple personality disorder

unspecified long-term societal changes. Unlike
depression or anxiety disorders, which have been
recognized, in some form, for centuries, the earliest
cases of persons reporting DID symptoms were not
recorded until the 1790s. Most were considered medical oddities or curiosities until the late 1970s, when
increasing numbers of cases were reported in the
United States. Psychiatrists are still debating whether
DID was previously misdiagnosed and underreported, or whether it is currently over-diagnosed.
Because childhood trauma is a factor in the development of DID, some doctors think it may be a variation of post-traumatic stress disorder (PTSD). DID
and PTSD are conditions where dissociation is a
prominent mechanism. The female to male ratio for
DID is about 9:1, but the reasons for the gender
imbalance are unclear. Some have attributed the
imbalance in reported cases to higher rates of abuse
of female children; and some to the possibility that
males with DID are underreported because they
might be in prison for violent crimes.

Multiple personality disorder

is subdued and withdrawn, particularly in female
patients. However, some core personalities, or alters,
may genuinely be depressed, and may benefit from
antidepressant medications. One reason misdiagnoses
are common is because DID patients may truly meet
the criteria for panic disorder or somatization disorder.
Misdiagnoses include schizophrenia, borderline
personality disorder, and, as noted, somatization disorder and panic disorder. DID patients are often
frightened by their dissociative experiences, which
can include losing awareness of hours or even days of
time, meeting people who claim to know them by
another name, or feeling ‘‘out of body.’’ Persons with
the disorder may go to emergency rooms or clinics
because they fear they are going insane.
When a doctor is evaluating a patient for DID, he
or she will first rule out physical conditions that sometimes produce amnesia, depersonalization, or derealization. These conditions include head injuries; brain
disease, especially seizure disorders; side effects from
medications; substance abuse or intoxication; AIDS
dementia complex; or recent periods of extreme physical stress and sleeplessness. In some cases, the doctor
may give the patient an electroencephalograph (EEG)
to exclude epilepsy or other seizure disorders. The
physician also must consider whether the patient is
malingering and/or offering fictitious complaints.
If the patient appears to be physically normal, the
doctor will next rule out psychotic disturbances, including schizophrenia. Many patients with DID are misdiagnosed as schizophrenic because they may ‘‘hear’’
their alters ‘‘talking’’ inside their heads. If the doctor
suspects DID, he or she can use a screening test called
the Dissociative Experiences Scale (DES). If the patient
has a high score on this test, he or she can be evaluated
further with the Dissociative Disorders Interview
Schedule (DDIS) or the Structured Clinical Interview
for DSM-IV Dissociative Disorders (SCID-D). The
doctor may also use the Hypnotic Induction Profile
(HIP) or a similar test of the patient’s hypnotizability.

Treatment
Treatment of DID may last for five to seven years
in adults and usually requires several different treatment methods.

addition, many patients with DID have hostile or
suicidal alter personalities. Most therapists who treat
DID patients have rules or contracts for treatment
that include such issues as the patient’s responsibility
for his or her safety. Psychotherapy for DID patients
typically has several stages: an initial phase for uncovering and ‘‘mapping’’ the patient’s alters; a phase of
treating the traumatic memories and ‘‘fusing’’ the
alters; and a phase of consolidating the patient’s
newly integrated personality.
Most therapists who treat multiples, or DID
patients, recommend further treatment after personality integration, on the grounds that the patient has
not learned the social skills that most people acquire in
adolescence and early adult life. In addition, family
therapy is often recommended to help the patient’s
family understand DID and the changes that occur
during personality reintegration.
Many DID patients are helped by group as well as
individual treatment, provided that the group is limited to people with dissociative disorders. DID
patients sometimes have setbacks in mixed therapy
groups because other patients are bothered or frightened by their personality switches.
Medications
Some doctors will prescribe tranquilizers or antidepressants for DID patients because their alter personalities may have anxiety or mood disorders. However,
other therapists who treat DID patients prefer to keep
medications to a minimum because these patients can
easily become psychologically dependent on drugs. In
addition, many DID patients have at least one alter who
abuses drugs or alcohol, substances which are dangerous in combination with most tranquilizers.
Hypnosis
While not always necessary, hypnosis is a standard method of treatment for DID patients. Hypnosis
may help patients recover repressed ideas and memories. Further, hypnosis can also be used to control
problematic behaviors that many DID patients exhibit, such as self-mutilation, or eating disorders like
bulimia nervosa. In the later stages of treatment, the
therapist may use hypnosis to ‘‘fuse’’ the alters as part
of the patient’s personality integration process.

Psychotherapy
Ideally, patients with DID should be treated by a
therapist with specialized training in dissociation. This
specialized training is important because the patient’s
personality switches can be confusing or startling. In
2502

Alternative treatment
Alternative treatments that help to relax the body
are often recommended for DID patients as an
adjunct to psychotherapy and/or medication. These
GALE ENCYCLOPEDIA OF MEDICINE

Alter—An alternate or secondary personality in a
patient with DID.
Amnesia—A general medical term for loss of memory that is not due to ordinary forgetfulness.
Amnesia can be caused by head injuries, brain
disease, or epilepsy as well as by dissociation.
Depersonalization—A dissociative symptom in
which the patient feels that his or her body is
unreal, is changing, or is dissolving.
Derealization—A dissociative symptom in which
the external environment is perceived as unreal.
Dissociation—A psychological mechanism that
allows the mind to split off traumatic memories or
disturbing ideas from conscious awareness.

adults. Although treatment takes several years, it is
often ultimately effective. As a general rule, the earlier
the patient is diagnosed and properly treated, the better the prognosis.

Prevention
Prevention of DID requires intervention in abusive families and treating children with dissociative
symptoms as early as possible.
Resources
BOOKS

Eisendrath, Stuart J. ‘‘Psychiatric Disorders.’’ In Current
Medical Diagnosis and Treatment, 1998, edited by
Stephen McPhee, et al., 37th ed. Stamford: Appleton &
Lange, 1997.

Rebecca J. Frey, PhD

Dissociative identity disorder (DID)—Term that
replaced Multiple Personality Disorder (MPD). A
condition in which two or more distinctive identities or personality states alternate in controlling a
person’s consciousness and behavior.
Hypnosis—An induced trance state used to treat
the amnesia and identity disturbances that occur
in dissociative identity disorder (DID).
Multiple personality disorder (MPD)—The former,
though often still used, term for dissociative identity
disorder (DID).
Primary personality—The core personality of an
DID patient. In women, the primary personality is
often timid and passive, and may be diagnosed as
depressed.
Trauma—A disastrous or life-threatening event
that can cause severe emotional distress. DID is
associated with trauma in a person’s early life or
adult experience.

treatments include hydrotherapy, botanical medicine
(primarily herbs that help the nervous system), therapeutic massage, and yoga. Homeopathic treatment
can also be effective for some people. Art therapy and
the keeping of journals are often recommended as
ways that patients can integrate their past into their
present life. Meditation is usually discouraged until the
patient’s personality has been reintegrated.

Prognosis
Some therapists believe that the prognosis for
recovery is excellent for children and good for most
GALE ENCYCLOPEDIA OF MEDICINE

Multiple pregnancy
Definition
Multiple pregnancy is a pregnancy where more
than one fetus develops simultaneously in the womb.

Description
Twins happen naturally about one in every 100
births. There are two types of twinning—identical and
fraternal. Identical twins represent the splitting of a
single fertilized zygote (union of two gametes or male/
female sex cells that produce a developing fetus) into
two separate individuals. They usually, but not
always, have identical genes. When they do not separate completely, the result is Siamese (or conjoined)
twins. Fraternal twins are three times as common as
identical twins. They occur when two eggs are fertilized by separate sperm. Each has a different selection
of its parents’ genes. The natural incidence of multiple
pregnancy has been upset by advances in fertility treatments, resulting in higher rates of multiple births in the
United States. All these children are fraternal; they
each arose from a separate egg and a separate sperm.
Cloning produces identical twins.
The human female is designed to release one egg
every menstrual cycle. A hormone called progesterone, released by the first egg to be produced, prevents
any other egg from maturing during that cycle. When
this control fails, fertilization of more than one egg is
2503

Multiple pregnancy

KEY TERMS

Multiple pregnancy

KEY TERMS

L O U I S G E R A L D K E I T H (1935– )
Louis Gerald Keith and his twin brother, Donald,
were born on April 24, 1935, to Russian immigrants.
Although the boys received much attention due to their
status as twins, their parents encouraged them to pursue
their own goals, and at age twelve, Louis decided he
wanted to become a doctor. After completing his bachelor of science degree at the University of Illinois, Keith
entered the Chicago Medical school, graduating with his
degree in 1960. He joined the U.S. Public Health Service
and was stationed in Puerto Rico after completing his
residency and internship at Cook County Hospital.
Keith returned to Chicago after receiving his certification
in obstetrics and gynecology in 1967 and worked as a
professor and a physician.
Keith began his research on twins when a friend’s twin
brother died of lymphoma. The fact that Keith was a twin
made his research more personally fulfilling and worthwhile to him. Keith and Donald founded the Center for
the Study of Multiple Birth in 1977 located in Chicago.
The center, a non-profit facility, was the first multiple birth
research organization in the United States. Keith has delivered many speeches and has published various study
results. In addition to books and scientific articles written
individually and cooperatively, he was co-author of
Multiple Pregnancy: Epidemiology, Gestation and
Prenatal Outcome (1996) with his brother Donald, and
others. He is currently the chief obstetrician at the Prentice
Women’s Hospital and Maternity Center in Chicago.

possible. Fertility drugs inhibit these controls, allowing multiple pregnancy to occur. Multiple pregnancy
is more difficult and poses more health risks than
single pregnancy. Premature birth is greater with
each additional fetus.
The problem with multiple births is that there is
only so much room in even the most accommodating
womb (uterus). Babies need to reach a certain size and
gestational age before they can survive outside the
uterus. Prematurity is the constant threat of multiple
pregnancies. Twins have five times the death rate of
single births. Triplets and higher die even more often.
The principle threat of prematurity is that the lungs
are not fully developed. A disease called hyaline membrane disease afflicts premature infants. Their lungs
do not stay open after their first breath because they
lack a chemical called surfactant. Survival of premature infants was greatly improved when surfactant was
finally synthesized in a form that could be of benefit to
premature babies. Tiny babies also have trouble regulating their body temperature.
2504

Amniotic membranes—A thin membrane surrounding the fetus and containing serous fluid.
Genes—Hereditary determinants of identifying
characteristics.
Gestational—Refers to pregnancy.
Ovulate—To release a mature egg for fertilization.
Zygote—The earliest stage of a fertilized egg.

Causes and symptoms
Fertility drugs prevent the normal process of single
ovulation by permitting more than one egg at a time to
mature and ovulate (move from the ovary to the uterus
in anticipation of fertilization). This happens naturally
to produce fraternal twins. The first drug to accomplish
this was clomiphene. Subsequently, two natural hormones—follicle stimulating hormone and chorionic
gonadotrophin—were developed and used.

Diagnosis
Multiple pregnancies cause the uterus to grow faster
than usual. Obstetricians can detect this unusually rapid
growth as the pregnancy progresses. Before birth, an
ultrasound will also detect multiple babies in the uterus.
After birth, physical appearance or a careful examination
of the placenta and amniotic membranes will usually
reveal whether the babies were in the same water bag or
separate ones. One bag means identical twins.
A multiple pregnancy almost always means
increased monitoring and surveillance for complications.
This often means more frequent visits to the healthcare
provider, serial ultrasounds to make sure that the babies
are growing adequately, amniocentesis to check for lung
development, and close monitoring for preterm labor.

Treatment
Mothers may be put on bedrest during a multiple
pregnancy, in order to try to try to prevent pre-term labor
and delivery. If preterm labor is impossible to control at
home, the mother may be hospitalized, and medication
may be used to attempt to control contractions and dilatation of the cervix. Multiple pregnancies more often end
in cesarean deliveries than singleton pregnancies.
Babies from multiple pregnancies are often born
early, and may require longer-than-normal hospitalization. The babies may need assistance with breathing,
careful control of body temperature within an
GALE ENCYCLOPEDIA OF MEDICINE

Multiple pregnancy
An ultrasound image of identical twin male fetuses. The distortion is due to ‘‘twin B’’ being closer to the monitor. (Courtesy of
Melissa Walsh Doig.)

incubator, and surveillance for other complications
that frequently beset pre-term babies. While premature babies are fragile in many other ways, modern
methods of intensive care have successfully stabilized
babies as small as one pound.

Alternative treatment
There are no specific treatments to alleviate medical difficulties caused by multiple pregnancies, however there are supportive measures that may help both
mother and children recover from the birthing process. There are treatments to encourage breast milk
production and to combat postpartum difficulties.
Various homeopathic remedies and massage can be
helpful to both mother and children during the early
adjustment period after birth.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
With modern medical advances and excellent prenatal care, many multiple pregnancies reach fruition
without difficulties. If the babies are born prematurely, immediate medical care increases the chance
of survival without any complications.
Resources
PERIODICALS

Evans, M.I., et al. ‘‘What Are the Ethical and Technical
Problems Associated with Multifetal Pregnancy
Reduction.’’ Clinical Obstetrics and Gynecology 41
(March 1998): 46-54.

Rosalyn Carson-DeWitt, MD
2505

Multiple sclerosis

Multiple sclerosis
Definition
Multiple sclerosis (MS) is a chronic autoimmune
disorder affecting movement, ensation, and bodily
functions. It is caused by destruction of the myelin
insulation covering nerve fibers (neurons) in the central nervous system (brain and spinal cord).

Description
MS is a nerve disorder caused by destruction of
the insulating layer surrounding neurons in the brain
and spinal cord. This insulation, called myelin, helps
electrical signals pass quickly and smoothly between
the brain and the rest of the body. When the myelin is
destroyed, nerve messages are sent more slowly and
less efficiently. Patches of scar tissue, called plaques,
form over the affected areas, further disrupting nerve
communication. The symptoms of MS occur when the
brain and spinal cord nerves no longer communicate
properly with other parts of the body. MS causes a
wide variety of symptoms and can affect vision, balance, strength, sensation, coordination, and bodily
functions.
Multiple sclerosis affects more than a quarter of a
million people in the United States. Most people have
their first symptoms between the ages of 20 and 40;
symptoms rarely begin before 15 or after 60. Women
are almost twice as likely to get MS as men, especially
in their early years. People of northern European heritage are more likely to be affected than people of other
racial backgrounds, and MS rates are higher in the
United States, Canada, and Northern Europe than in
other parts of the world. MS is very rare among
Asians, North and South American Indians, and
Eskimos.

Causes and symptoms
Causes
Multiple sclerosis is an autoimmune disease,
meaning its cause is an attack by the body’s own
immune system. For unknown reasons, immune cells
attack and destroy the myelin sheath that insulates
neurons in the brain and spinal cord. This myelin
sheath, created by other brain cells called glia, speeds
transmission and prevents electrical activity in one cell
from short-circuiting to another cell. Disruption of
communication between the brain and other parts of
the body prevent normal passage of sensations and
control messages, leading to the symptoms of MS.
2506

The demyelinated areas appear as plaques, small
round areas of gray neuron without the white myelin
covering. The progression of symptoms in MS is correlated with development of new plaques in the portion of the brain or spinal cord controlling the affected
areas. Because there appears to be no pattern in the
appearance of new plaques, the progression of MS can
be unpredictable.
Despite considerable research, the trigger for this
autoimmune destruction is still unknown. At various
times, evidence has pointed to genes, environmental
factors, viruses, or a combination of these.
The risk of developing MS is higher if another
family member is affected, suggesting the influence of
genetic factors. In addition, the higher prevalence of
MS among people of northern European background
suggests some genetic susceptibility.
The role of an environmental factor is suggested
by studies of the effect of migration on the risk of
developing MS. Age plays an important role in determining this change in risk—young people in low-risk
groups who move into countries with higher MS rates
display the risk rates of their new surroundings, while
older migrants retain the risk of their original home
country. One interpretation of these studies is that an
environmental factor, either protective or harmful, is
acquired in early life; the risk of disease later in life
reflects the effects of the early environment.
These same data can be used to support the involvement of a slow-acting virus, one that is acquired
early on but begins its destructive effects much later.
Slow viruses are known to cause other diseases, including AIDS. In addition, viruses have been implicated in
other autoimmune diseases. Many claims have been
made for the role of viruses, slow or otherwise, as the
trigger for MS, but as of 2001 no strong candidate has
emerged.
How a virus could trigger the autoimmune reaction is also unclear. There are two main models of
virally induced autoimmunity. The first suggests the
immune system is actually attacking a virus (one too
well-hidden for detection in the laboratory), and the
myelin damage is an unintentional consequence of
fighting the infection. The second model suggests the
immune system mistakes myelin for a viral protein,
one it encountered during a prior infection. Primed for
the attack, it destroys myelin because it resembles the
previously-recognized viral invader.
Either of these models allows a role for genetic
factors, since certain genes can increase the likelihood
of autoimmunity. Environmental factors as well might
change the sensitivity of the immune system or interact
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms
The symptoms of multiple sclerosis may occur in
one of three patterns:


The most common pattern is the ‘‘relapsingremitting’’ pattern, in which there are clearly defined
symptomatic attacks lasting 24 hours or more, followed by complete or almost complete improvement.
The period between attacks may be a year or more at
the beginning of the disease, but may shrink to several months later on. This pattern is especially common in younger people who develop MS.



In the ‘‘primary progressive’’ pattern, the disease
progresses without remission or with occasional plateaus or slight improvements. This pattern is more
common in older people.



In the ‘‘secondary progressive’’ pattern, the person
with MS begins with relapses and remissions, followed by more steady progression of symptoms.

Between 10–20% of people have a benign type of
MS, meaning their symptoms progress very little over
the course of their lives.
Because plaques may form in any part of the
central nervous system, the symptoms of MS vary
widely from person-to-person and from stage-tostage of the disease. Initial symptoms often include:


Muscle weakness, causing difficulty walking



Loss of coordination or balance



Numbness, ‘‘pins and needles,’’ or other abnormal
sensations



Visual disturbances, including blurred or double
vision.
Later symptoms may include:



Fatigue



Muscle spasticity and stiffness



Tremors



Paralysis



Pain



Vertigo



Speech or swallowing difficulty



Loss of bowel and bladder control



Incontinence, constipation

GALE ENCYCLOPEDIA OF MEDICINE



Sexual dysfunction



Cognitive changes.

Weakness in one or both legs is common, and may
be the first symptom noticed by a person with MS.
Muscle spasticity, or excessive tightness, is also common and may be more disabling than weakness.
Double vision or eye tremor (nystagmus) may
result from involvement of the nerve pathways controlling movement of the eye muscles. Visual disturbances result from involvement of the optic nerves
(optic neutritis) and may include development of
blind spots in one or both eyes, changes in color vision,
or blindness. Optic neuritis usually involves only one
eye at a time and is often associated with movement of
the effected eye.
More than half of all people affected by MS have
pain during the course of their disease, and many
experience chronic pain, including pain from
spasticity. Acute pain occurs in about 10% of cases.
This pain may be a sharp, stabbing pain especially in
the face, neck, or down the back. Facial numbness and
weakness are also common.
Cognitive changes, including memory disturbances, depression, and personality changes, are found
in people affected by MS, though it is not entirely clear
whether these changes are due primarily to the disease
or to the psychological reaction to it. Depression may
be severe enough to require treatment in up to 25% of
those with MS. A smaller number of people experience
disease-related euphoria, or abnormally elevated mood,
usually after a long disease duration and in combination
with other psychological changes.
Symptoms of MS may be worsened by heat or
increased body temperature, including fever, intense physical activity, or exposure to sun, hot baths, or showers.

Diagnosis
There is no single test that confirms the diagnosis
of multiple sclerosis, and there are a number of other
diseases with similar symptoms. While one person’s
diagnosis may be immediately suggested by her symptoms and history, another’s may not be confirmed
without multiple tests and prolonged observation.
The distribution of symptoms is important: MS affects
multiple areas of the body over time. The pattern of
symptoms is also critical, especially evidence of the
relapsing- remitting pattern, so a detailed medical history is one of the most important parts of the diagnostic process. A thorough search to exclude other causes
of a patient’s symptoms is especially important if the
following features are present: 1) family history of
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Multiple sclerosis

with myelin to provide the trigger for the secondary
immune response. Possible environmental triggers that
have been invoked in MS include viral infection, trauma,
electrical injury, and chemical exposure, although controlled studies do not support a causative role.

Multiple sclerosis

neurologic disease, 2) symptoms and findings attributable to a single anatomic location, 3) persistent back
pain, 4) age of onset over 60 or under 15 years of age,
or 5) progressively worsening disease.
In addition to the medical history and a standard
neurological exam, several lab tests are used to help
confirm or rule out a diagnosis of MS:


Magnetic resonance imaging (MRI) can reveal plaques on the brain and spinal cord. Gadolinium
enhancement can distinguish between old and new
plaques, allowing a correlation of new plaques withnew symptoms. Plaques may be seen in several otherdiseases as well, including encephalomyelitis,
neurosarcoidosis, and cerebral lupus. Plaques on
MRI may be difficult to distinguish from small
strokes, areas of decreased blood flow, or changes
seen with trauma or normal aging.



A lumbar puncture, or spinal tap, is done to measure
levels of immune proteins, which are usually elevated
in the cerebrospinal fluid of a person with MS. This
test may not be necessary if other tests are diagnostic.



Evoked potential tests, electrical tests of conduction
speed in the nerves, can reveal reduced speeds consistent with the damage caused by plaques. These
tests may be done with small electrical charges
applied to the skin (somatosensory evoked potential), with light patterns flashed on the eyes (visual
evoked potential), or with sounds presented to the
ears (auditory evoked potential).

The clinician making the diagnosis, usually a neurologist, may classify the disease as ‘‘definite MS,’’
meaning the symptoms and test results all point
toward MS as the cause. ‘‘Probable MS’’ and ‘‘possible MS’’ reflect less certainty and may require more
time to pass to observe the progression of the disease
and the distribution of symptoms.

Treatment
The three major drugs previously approved for
the treatment of MS affect the course of the disease.
None of these drugs is a cure, but they can slow disease
progression in many patients.
Known as the ABC drugs, Avonex and Betaseron
are forms of the immune system protein beta interferon, while Copaxone is glatiramer acetate (formerly
called copolymer-1). All three have been shown to
reduce the rate of relapses in the relapsing-remitting
form of MS. Different measurements from tests of
each have demonstrated other benefits as well:
Avonex may slow the progress of physical impairment, Betaseron may reduce the severity of symptoms,
2508

and Copaxone may decrease disability. All three drugs
are administered by injection
Two major clinical studies were recently completed that focused on the question of whether disease-modifying therapy known to slow the disease,
can postpone the development of clinically definitive
MS in high risk patients. Data presented at the annual
meeting of the American Academy of Neurology in
May, 2000, highlighted the different effects of interferon therapy when it was initiated at the earliest
recognizable stages of MS versus later. Previous studies with interferon beta-1b (Betaseron) and interferon beta-1a (Avonex, Rebif) clearly demonstrated
benefits in patients with relapsing forms of MS.
Moreover, previous treatment with High-dose corticosteroids also delays, but does not prevent the ultimate development of MS. The encouraging message
from the CHAMPS study in the United states and the
ETOMS study in Europe is that early intervention can
reduce the probability of developing clinically definitive MS.
Although the ABC drugs stop relapses and may
keep patients in relatively good health for the shortterm, their long-term success has not been proven and
they don’t work well for patients who have reached a
steadily progressive stage of MS. In the meantime, new
approaches to using current therapies are being
researched especially using combinations of different
types of agents when one agent alone is not effective.
Clinical trials are now evaluating the safety and efficacy of combining cyclophosphamide (Cytoxan) and
methylprednisolone (Medrol) in patients who do not
respond to the ABC drus, and of adding mitoxantrone
(Novantrone), prednisone (Prelone), azathioprine
(Imuran), or methotrexate (Rheumatrex) to betainterferon for further benefit.
In addition, Miloxzantrone HCI (novantrone), a
drug approved for cancer treatment, has been approved
for treating patients with advanced or chronic multiple
scelereosis.In clinical trials, mitoxantrone reduced the
number of relapse episodes and slowed down the disease. Reserved for progressive forms of MS, it is given
intravenously by a doctor to help maintain mobility and
reduce the number of flare-ups. However, there are
serious side effects with the drug including heart problems, nausea, and hair thinning.
As reported in the Spring, 2001, Volume 19, No
2 issue of InsideMS, the FDA recently approved the
Copaxone Autoject and the Mixject vial adapters to
help people using Copaxone self administer the drug.
The autoject keeps the syringe steady and hides the
needle. The same syringe may be used for both mixing
GALE ENCYCLOPEDIA OF MEDICINE

Absence of
myelin sheath

Nerve cell

Multiple sclerosis (MS) is an autoimmune disease in which immune cells attack and destroy the myelin sheath which stimulates
neurons in the brain and spinal cord. When the myelin is destroyed, nerve messages are sent more slowly and less efficiently.
Scar tissue then forms over the affected areas, disrupting nerve communication. MS symptoms occur when the brain and spinal
cord nerves cease to communicate properly with other parts of the body. (Illustration by Electronic Illustrators Group.)

and injecting with the Mixject vial adapters. A similar
device is available for patients using Betassseron.
Some patients are using the needlefree Biojector 2000
which uses a CO2 cartridge to deliver doses of medication through the skin. The FDA has not approved
its use and patients should discuss this with their physician for its use with either Copaxone or Betaseron.
Avonex must be injected in the muscle.
Immunosuppressant drugs have been used for
many years to treat acute exacerbations (relapses).
Drugs used include corticosteroids such as prednisone
and methylprednisone; the hormone adrenocorticotropic hormone (ACTH); and azathioprine. Recent
studies indicate that several days of intravenous
methylprednisone may be more effective than other
immunosuppressant treatments for acute symptoms.
This treatment may require hospitalization.
GALE ENCYCLOPEDIA OF MEDICINE

MS causes a large variety of symptoms, and the
treatments for these are equally diverse. Most
symptoms can be treated and complications
avoided with good care and attention from medical
professionals. Good health and nutrition remain
important preventive measures. Vaccination against
influenza can prevent respiratory complications,
and contrary to earlier concerns, is not associated
with worsening of symptoms. Preventing complications such as pneumonia, bed sores, injuries from
falls, or urinary infection requires attention to the
primary problems which may cause them.
Shortened life spans with MS are almost always
due to complications rather than primary symptoms
themselves.
Physical therapy helps the person with MS to
strengthen and retrain affected muscles; to maintain
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Multiple sclerosis

Myelin sheath

Multiple sclerosis

range of motion to prevent muscle stiffening; to learn
to use assistive devices such as canes and walkers; and
to learn safer and more energy-efficient ways of moving, sitting, and transferring. Exercise and stretching
programs are usually designed by the physical therapist and taught to the patient and caregivers for use at
home. Exercise is an important part of maintaining
function for the person with MS. Swimming is often
recommended, not only for its low-impact workout,
but also because it allows strenuous activity without
overheating.
Occupational therapy helps the person with MS
adapt to her environment and adapt the environment to her. The occupational therapist suggests
alternate strategies and assistive devices for activities
of daily living, such as dressing, feeding, and washing, and evaluates the home and work environment
for safety and efficiency improvements that may
be made.
Training in bowel and bladder care may be
needed to prevent or compensate for incontinence.
If the urge to urinate becomes great before the bladder is full, some drugs may be helpful, including
propantheline bromide (Probanthine), oxybutynin
chloride (Ditropan), or imipramine (Tofranil).
Baclofen (Lioresal) may relax the sphincter muscle,
allowing full emptying. Intermittent catheterization
is effective in controlling bladder dysfunction. In this
technique, a catheter is used to periodically empty the
bladder.
Spasticity can be treated with oral medications,
including baclofen and diazepam (Valium), or by
injection with botulinum toxin (Botox). Spasticity
relief may also bring relief from chronic pain. Other
more acute types of pain may respond to carbamazepine (Tegretol) or diphenylhydantoin (Dilantin).
Low back pain is common from increased use of the
back muscles to compensate for weakened legs.
Physical therapy and over-the-counter pain relievers
may help.

Alternative treatment
Bee venom has been suggested as a treatment for
MS, but no studies or objective reports support this
claim.
In British studies, marijuana has been shown to
have variable effects on the symptoms of MS.
Improvements have been documented for tremor,
pain, and spasticity, and worsening for posture and
balance. Side effects have included weakness, dizziness, relaxation, and incoordination, as well as
euphoria. As a result, marijuana is not recommended
as an alternative treatment.
Some studies support the value of high doses of
vitamins, minerals, and other dietary supplements for
controlling disease progression or improving symptoms. Alpha-linoleic and linoleic acids, as well as selenium and vitamin E, have shown effectiveness in the
treatment of MS. The selenium and vitamin E act as
antioxidants. In addition, the Swank diet (low in saturated fats), maintained over a long period of time, may
retard the disease process.
Removal of mercury fillings has been touted as a
possible cure, but is of no proven benefit.
Studies have also shown that t’ai chi can be an
effective therapy for MS because it works to improve
balance and increase strength.
There are conflicting views about Echinacea and
its benefit to MS. Some medicine books recommend
Echinacea for people with MS. However, Echinacea
appears to stimulate different parts of the immune
system, particularly immune cells known as macrophages. In MS these cells are very active already and
further stimulation could worsen the disease.

Prognosis

Fatigue may be partially avoidable with changes
in the daily routine to allow more frequent rests.
Amantadine (Symmetrel) and pemoline (Cylert) may
improve alertness and lessen fatigue. Visual disturbances often respond to corticosteroids. Other symptoms that may be treated with drugs include seizures,
vertigo, and tremor.

It is difficult to predict how multiple sclerosis will
progress in any one person. Most people with MS will
be able to continue to walk and function at their work
for many years after their diagnosis. The factors associated with the mildest course of MS are being female,
having the relapsing-remitting form, having the first
symptoms at a younger age, having longer periods of
remission between relapses, and initial symptoms of
decreased sensation or vision rather than of weakness
or incoordination.

Myloral, an oral preparation of bovine myelin,
has recently been tested in clinical trials for its effectiveness in reducing the frequency and severity of
relapses. Preliminary data indicate no difference
between it and placebo.

Less than 5% of people with MS have a severe
progressive form, leading to death from complications
within five years. At the other extreme, 10–20% have a
benign form, with a very slow or no progression of
their symptoms. The most recent studies show that

2510

GALE ENCYCLOPEDIA OF MEDICINE

Clinical trial—All new drugs undergo clinical trials
before approval. Clinical trials are carefully conducted tests in which effectiveness and side effects
are studied, with the placebo effect eliminated.
Evoked potentials—Tests that measure the brain’s
electrical response to stimulation of sensory organs
(eyes or ears) or peripheral nerves (skin). These tests
may help confirm the diagnosis of multiple
sclerosis.
Myelin—A layer of insulation that surrounds the
nerve fibers in the brain and spinal cord.
Plaque—Patches of scar tissue that form where the
layer of yelin covering the nerve fibers is destroyed
by the multiple sclerosis disease process.
Primary progressive—A pattern of symptoms of
multiple sclerosis in which the disease progresses
without remission, or with occasional plateaus or
slight improvements.
Relapsing-remitting—A pattern of symptoms of
multiple sclerosis in which symptomatic attacks
occur that last 24 hours or more, followed by complete or almost complete improvement.
Secondary progressive—A pattern of symptoms of
multiple sclerosis in which there are relapses and
remissions, followed by more steady progression of
symptoms.

about seven out of 10 people with MS are still alive
25 years after their diagnosis, compared to about nine
out of 10 people of similar age without disease. On
average, MS shortens the lives of affected women by
about six years, and men by 11 years. Suicide is a significant cause of death in MS, especially in younger patients.
The degree of disability a person experiences five
years after onset is, on average, about three-quarters
of the expected disability at 10–15 years. A benign
course for the first five years usually indicates the
disease will not cause marked disability.

Prevention
There is no known way to prevent multiple sclerosis. Until the cause of the disease is discovered, this is
unlikely to change. Good nutrition; adequate rest;
avoidance of stress, heat, and extreme physical exertion; and good bladder hygiene may improve quality
of life and reduce symptoms.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Kraft, Georg H., and Marci Catanzaro. Living with Multiple
Sclerosis: A Wellness Approach. Demos Medical
Publishing, 2000.

Ruthan Brodsky

Mumps
Definition
Mumps is a relatively mild short-term viral infection of the salivary glands that usually occurs during
childhood. Typically, mumps is characterized by a
painful swelling of both cheek areas, although the
person could have swelling on one side or no perceivable swelling at all. The salivary glands are also called
the parotid glands, therefore, mumps is sometimes
referred to as an inflammation of the parotid glands
(epidemic parotitis). The word mumps comes from an
old English dialect, meaning lumps or bumps within
the cheeks.

Description
Mumps is a very contagious infection that spreads
easily in such highly populated areas as day care centers and schools. Although not as contagious as
measles or chickenpox, mumps was once quite common. Prior to the release of a mumps vaccine in the
United States in 1967, approximately 92% of all children had been exposed to mumps by the age of 15. In
these pre-vaccine years, most children contracted
mumps between the ages of four and seven. Mumps
epidemics came in two to five year cycles. The greatest
mumps epidemic was in 1941 when approximately 250
cases were reported for every 100,000 people. In 1968,
the year after the live mumps vaccine was released,
only 76 cases were reported for every 100,000 people.
By 1985, less than 3,000 cases of mumps were reported
throughout the entire United States, which works out
to about 1 case per 100,000 people. The reason for the
decline in mumps was the increased usage of the
mumps vaccine. However, 1987 noted a five-fold
increase in the incidence of the disease because of the
reluctance of some states to adopt comprehensive
school immunization laws. Since then, state-enforced
school entry requirements have achieved student
immunization rates of nearly 100% in kindergarten
and first grade. In 1996, the Centers for Disease
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Mumps

Resources

KEY TERMS

Mumps

Control and Prevention (CDC) reported only 751
cases of mumps nationwide, or, in other words,
about one case for every five million people.

Causes and symptoms
The paramyxovirus that causes mumps is harbored in the saliva and is spread by sneezing, coughing, and other direct contact with another person’s
infected saliva. Once the person is exposed to the
virus, symptoms generally occur in 14-24 days.
Initial symptoms include chills, headache, loss of
appetite, and a lack of energy. However, an infected
person may not experience these initial symptoms.
Swelling of the salivary glands in the face (parotitis)
generally occurs within 12-24 hours of the above
symptoms. Accompanying the swollen glands is
pain on chewing or swallowing, especially with acidic
beverages, such as lemonade. A fever as high as 1048F
(408C) is also common. Swelling of the glands reaches
a maximum on about the second day and usually
disappears by the seventh day. Once a person has
contracted mumps, they become immune to the disease, despite how mild or severe their symptoms may
have been.
While the majority of cases of mumps are uncomplicated and pass without incident, some complications can occur. Complications are, however, more
noticeable in adults who get the infection. In 15% of
cases, the covering of the brain and spinal cord
becomes inflamed (meningitis). Symptoms of meningitis usually develop within four or five days after the
first signs of mumps. These symptoms include a stiff
neck, headache, vomiting, and a lack of energy.
Mumps meningitis is usually resolved within seven
days, and damage to the brain is exceedingly rare.
The mumps infection can spread into the brain
causing inflammation of the brain (encephalitis).
Symptoms of mumps encephalitis include the inability
to feel pain, seizures, and high fever. Encephalitis can
occur during the parotitis stage or one to two weeks
later. Recovery from mumps encephalitis is usually
complete, although complications, such as seizure disorders, have been noted. Only about 1 in 100 with
mumps encephalitis dies from the complication.
About one-quarter of all post-pubertal males who
contract mumps can develop a swelling of the scrotum
(orchitis) about seven days after the parotitis stage.
Symptoms include marked swelling of one or both
testicles, severe pain, fever, nausea, and headache.
Pain and swelling usually subside after five to seven
days, although the testicles can remain tender for
weeks.
2512

Girls occasionally suffer an inflammation of the
ovaries, or oophoritis, as a complication of mumps,
but this condition is far less painful than orchitis in
boys.
As of late 2002, some researchers in Europe are
studying the possibility that mumps increases a person’s risk of developing inflammatory bowel disease
(IBD) in later life. This hypothesis will require further
research, as present findings are inconclusive.

Diagnosis
When mumps reaches epidemic proportions,
diagnosis is relatively easy on the basis of the physical
symptoms. The doctor will take the child’s temperature, gently palpate (touch) the skin over the parotid
glands, and look inside the child’s mouth. If the child
has mumps, the openings to the ducts inside the mouth
will be slightly inflamed and have a ‘‘pouty’’ appearance. With so many people vaccinated today, a case of
mumps must be properly diagnosed in the event the
salivary glands are swollen for reasons other than viral
infection. For example, in persons with poor oral
hygiene, the salivary glands can be infected with bacteria. In these cases, antibiotics are necessary. Also in
rare cases, the salivary glands can become blocked,
develop tumors, or swell due to the use of certain
drugs, such as iodine. A test can be performed to
determine whether the person with swelling of the
salivary glands actually has the mumps virus.
As of late 2002, researchers in London have
reported the development of a bioassay for measuring
mumps-specific IgG. This test would allow a doctor to
check whether an individual patient is immune to
mumps, and allow researchers to measure the susceptibility of a local population to mumps in areas with
low rates of vaccination.

Treatment
When mumps does occurs, the illness is usually
allowed to run its course. The symptoms, however, are
treatable. Because of difficulty swallowing, the most
important challenge is to keep the patient fed and
hydrated. The individual should be provided a soft
diet, consisting of cooked cereals, mashed potatoes,
broth-based soups, prepared baby foods, or foods put
through a home food processor. Aspirin, acetaminophen, or ibuprofen can relieve some of the pain due to
swelling, headache, and fever. Avoid fruit juices and
other acidic foods or beverages that can irritate the
salivary glands. Avoid dairy products that can be hard
to digest. In the event of complications, a physician
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
When mumps is uncomplicated, prognosis is
excellent. However, in rare cases, a relapse occurs
after about two weeks. Complications can also delay
complete recovery.
A young child with mumps. (Photo Researchers. Reproduced
by permission.)

should be contacted at once. For example, if orchitis
occurs, a physician should be called. Also, supporting
the scrotum in a cotton bed on an adhesive-tape bridge
between the thighs can minimize tension. Ice packs are
also helpful.

Alternative treatment
Acupressure can be used effectively to relieve pain
caused by swollen glands. The patient can, by using
the middle fingers, gently press the area between the
jawbone and the ear for two minutes while breathing
deeply.
A number of homeopathic remedies can be used
for the treatment of mumps. For example, belladonna
may be useful for flushing, redness, and swelling.
Bryonia (wild hops) may be useful for irritability,
lack of energy, or thirst. Phytolacca (poke root) may
be prescribed for extremely swollen glands. A homeopathic physician should always be consulted for
appropriate doses for children, and remedies that do
not work within one day should be stopped. A homeopathic preparation of the mumps virus can also be
used prophylactically or as a treatment for the disease.
Several herbal remedies may be useful in helping
the body recover from the infection or may help alleviate the discomfort associated with the disease.
Echinacea (Echinacea spp.) can be used to boost the
immune system and help the body fight the infection.
Other herbs taken internally, such as cleavers (Galium
aparine), calendula (Calendula officinalis), and phytolacca (poke root), target the lymphatic system and
may help to enhance the activity of the body’s internal
filtration system. Since phytolacca can be toxic, it
should only be used by patients under the care of a
skilled practitioner. Topical applications are also
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
A vaccine exists to protect against mumps. The
vaccine preparation (MMR) is usually given as part of
a combination injection that helps protect against
measles, mumps, and rubella. MMR is a live vaccine
administered in one dose between the ages of 12-15
months, 4-6 years, or 11-12 years. Persons who are
unsure of their mumps history and/or mumps vaccination history should be vaccinated. Susceptible health
care workers, especially those who work in hospitals,
should be vaccinated. Because mumps is still prevalent
throughout the world, susceptible persons over age
one who are traveling abroad would benefit from
receiving the mumps vaccine.
The mumps vaccine is extremely effective, and
virtually everyone should be vaccinated against this
disease. There are, however, a few reasons why people
should not be vaccinated against mumps:


Pregnant women who contract mumps during pregnancy have an increased rate of miscarriage, but not
birth defects. As a result, pregnant women should not
receive the mumps vaccine because of the possibility
of damage to the fetus. Women who have had the
vaccine should postpone pregnancy for three months
after vaccination.



Unvaccinated persons who have been exposed to
mumps should not get the vaccine, as it may not
provide protection. The person should, however, be
vaccinated if no symptoms result from the exposure
to mumps.



Persons with minor fever-producing illnesses, such as
an upper respiratory infection, should not get the
vaccine until the illness has subsided.



Because mumps vaccine is produced using eggs, individuals who develop hives, swelling of the mouth or
throat, dizziness, or breathing difficulties after eating
eggs should not receive the mumps vaccine.
2513

Mumps

useful in relieving the discomfort of mumps. A cloth
dipped in a heated mixture of vinegar and cayenne
(Capsicum frutescens) can be wrapped around the
neck several times a day. Cleavers or calendula can
also be combined with vinegar, heated, and applied in
a similar manner.

Mumps

KEY TERMS
Asymptomatic—Persons who carry a disease and
may be capable of transmitting the disease but who
do not exhibit symptoms of the disease are said to be
asymptomatic.
Autism—A severe developmental disorder that
usually begins before three years of age and affects
a child’s social as well as intellectual development.
Some researchers theorized that immunization with
the MMR vaccine was a risk factor for autism.
Encephalitis—Inflammation of the brain.
Epidemic parotitis—The medical name for mumps.
Immunoglobulin G (IgG)—A group of antibodies
against certain viral infections that circulate in the
bloodstream. One type of IgG is specific against the
mumps paramyxovirus.
Meningitis—Inflammation of the membranes covering the brain and spinal cord.
Orchitis—Inflammation or swelling of the scrotal
sac containing the testicles.
Paramyxovirus—A genus of viruses that includes
the causative agent of mumps.
Parotitis—Inflammation and swelling of the salivary glands.



Persons with immune deficiency diseases and/or
those whose immunity has been suppressed with
anti-cancer drugs, corticosteroids, or radiation
should not receive the vaccine. Family members of
immunocompromised people, however, should get
vaccinated to reduce the risk of mumps.



The CDC recommends that all children infected with
human immunodeficiency disease (HIV) who are
asymptomatic should receive an the MMR vaccine
at 15 months of age.

The mumps vaccine has been controversial in
recent years because of concern that its use was linked
to a rise in the rate of childhood autism. The negative
publicity given to the vaccine in the mass media led
some parents to refuse to immunize their children
with the MMR vaccine. One result has been an
increase in the number of mumps outbreaks in several
European countries, including Italy and the United
Kingdom.
In the fall of 2002, the New England Journal of
Medicine published a major Danish study disproving
2514

the hypothesis of a connection between the MMR
vaccine and autism. A second study in Finland showed
that the vaccine is not associated with aseptic meningitis or encephalitis as well as autism. Since these
studies were published, American primary care physicians have once again reminded parents of the importance of immunizing their children against mumps and
other childhood diseases.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Viral Infections: Mumps.’’ Section 19, Chapter 265. In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Gabutti, G., M. C. Rota, S. Salmaso, et al. ‘‘Epidemiology
of Measles, Mumps and Rubella in Italy.’’
Epidemiology and Infection 129 (December 2002): 543–
550.
Kimmel, S. R. ‘‘Vaccine Adverse Events: Separating Myth
From Reality.’’ American Family Physician 66
(December 1, 2002): 2113–2120.
Madsen, K. M., A. Hviid, M. Vestergaard, et al. ‘‘A
Population-Based Study of Measles, Mumps, and
Rubella Vaccination and Autism.’’ New England
Journal of Medicine 347 (November 7, 2002): 1477–
1482.
Makela, A., J. P. Nuorti, and H. Peltola. ‘‘Neurologic
Disorders After Measles-Mumps-Rubella
Vaccination.’’ Pediatrics 110 (November 2002): 957–
963.
McKie, A., D. Samuel, B. Cohen, and N. A. Saunders.
‘‘A Quantitative Immuno-PCR Assay for the Detection
of Mumps-Specific IgG.’’ Journal of Immunological
Methods 270 (December 1, 2002): 135–141.
Nielsen, S. E., O. H. Nielsen, B. Vainer, and M. H. Claesson.
‘‘Inflammatory Bowel Disease—Do Microorganisms
Play a Role?’’ [in Danish] Ugeskrift for laeger 164
(December 9, 2002): 5947–5950.
Pugh, R. N., B. Akinosi, S. Pooransingh, et al. ‘‘An
Outbreak of Mumps in the Metropolitan Area of
Walsall, UK.’’ International Journal of Infectious
Diseases 6 (December 2002): 283–287.
ORGANIZATIONS

American Academy of Pediatrics (AAP). 141 Northwest
Point Boulevard, Elk Grove Village, IL 60007. (847)
434-4000. <www.aap.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Ron Gasbarro, PharmD
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Munchausen syndrome is a psychiatric disorder
that causes an individual to self-inflict injury or illness
or to fabricate symptoms of physical or mental illness,
in order to receive medical care or hospitalization. In a
variation of the disorder, Munchausen by proxy
(MSBP), an individual, typically a mother, intentionally causes or fabricates illness in a child or other
person under her care.

Description
Munchausen syndrome takes its name from
Baron Karl Friederich von Munchausen, an 18th century German military man known for his tall tales.
The disorder first appeared in psychiatric literature in
the early 1950s when it was used to describe patients
who sought hospitalization by inventing symptoms
and complicated medical histories, and/or inducing
illness and injury in themselves. Categorized as a factitious disorder (a disorder in which the physical or
psychological symptoms are under voluntary control),
Munchausen’s syndrome seems to be motivated by a
need to assume the role of a patient. Unlike malingering, there does not seem to be any clear secondary gain
(e.g., money) in Munchausen syndrome.
Individuals with Munchausen by proxy syndrome
use their child (or another dependent person) to fulfill
their need to step into the patient role. The disorder
most commonly victimizes children from birth to
8 years old. Parents with MSBP may only exaggerate
or fabricate their child’s symptoms, or they may deliberately induce symptoms through various methods,
including poisoning, suffocation, starvation, or infecting the child’s bloodstream.

Apnea—A cessation of breathing.
Factitious disorder—A disorder in which the physical or psychological symptoms are under voluntary control.

and symptoms. Some common complaints include
fevers, rashes, abscesses, bleeding, and vomiting.
Common Munchausen by proxy symptoms include
apnea (cessation of breathing), fever, vomiting, and
diarrhea. In both Munchausen and MSBP syndromes,
the suspected illness does not respond to a normal
course of treatment. Patients or parents may push
for invasive diagnostic procedures and display an
extraordinary depth of knowledge of medical
procedures.

Diagnosis
Because Munchausen sufferers often go from doctor to doctor, gaining admission into many hospitals
along the way, diagnosis can be difficult. They are
typically detected rather than diagnosed. During a
course of treatment, they may be discovered by
a hospital employee who encountered them during a
previous hospitalization. Their caregivers may also
notice that symptoms such as high fever occur only
when the patient is left unattended. Occasionally,
unprescribed medication used to induce symptoms is
found with the patient’s belongings. When the patient
is confronted, they often react with outrage and check
out of the hospital to seek treatment at another facility
with a new caregiver.

Treatment
Causes and symptoms
The exact cause of Munchausen syndrome is
unknown. It has been theorized that Munchausen
patients are motivated by a desire to be cared for, a
need for attention, dependency, an ambivalence
toward doctors, or a need to suffer. Factors that may
predispose an individual to Munchausen’s include a
serious illness in childhood or an existing personality
disorder.
The Munchausen patient presents a wide array of
physical or psychiatric symptoms, usually limited only
by their medical knowledge. Many Munchausen
patients are very familiar with medical terminology
GALE ENCYCLOPEDIA OF MEDICINE

There is no clearly effective treatment for
Munchausen syndrome. Extensive psychotherapy
may be helpful with some Munchausen patients. If
Munchausen syndrome co-exists with other mental
disorders, such as a personality disorder, the underlying disorder is typically treated first.

Prognosis
The infections and injuries Munchausen patients
self-inflict can cause serious illness. Patients often
undergo countless unnecessary surgeries throughout
their lifetimes. In addition, because of their frequent
hospitalizations, they have difficulty holding down a
2515

Munchausen syndrome

KEY TERMS

Munchausen syndrome

Muscle relaxants

job. Further, their chronic health complaints may
damage interpersonal relationships with family and
friends. Children victimized by sufferers of MSBP
are at a real risk for serious injury and possible
death. Those who survive physically unscathed may
suffer developmental problems later in life.

Prevention
Because the cause of Munchausen syndrome is
unknown, formulating a prevention strategy is difficult.
Some medical facilities and healthcare practitioners have
attempted to limit hospital admissions for Munchausen
patients by sharing medical records. While these
attempts may curb the number of hospital admissions,
they do not treat the underlying disorder and may
endanger Munchausen sufferers that have made themselves critically ill and require treatment. Children who
are found to be victims of persons with Munchausen by
proxy syndrome should be immediately removed from
the care of the abusing parent or guardian.
Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Paula Anne Ford-Martin

They are a separate class of drugs from the muscle
relaxant drugs used during intubations and surgery to
reduce the need for anesthesia and facilitate
intubation.

Purpose
Skeletal muscle relaxants may be used for relief of
spasticity in neuromuscular diseases, such as multiple
sclerosis, as well as for spinal cord injury and stroke.
They may also be used for pain relief in minor strain
injuries and control of the muscle symptoms of tetanus. Dantrolene (Dantrium) has been used to prevent
or treat malignant hyperthermia in surgery.

Description
Although the muscle relaxants may be divided
into only two groups, centrally acting and peripherally
acting, the centrally acting group, which appears to act
on the central nervous system, contains 10 drugs
which are chemically different, while only dantrolene
has a direct action at the level of the nerve-muscle
connection.
Baclofen (Lioresal) may be administered orally or
intrathecally for control of spasticity due to neuromuscular disease.
Carisoprodol (Soma), chlorphenesin (Maolate),
chlorzoxazone (Paraflex), cyclobenzaprine (Flexeril),
diazepam (Valium), metaxalone (Skelaxin), methocarbamol (Robaxin), and orphenadrine (Norflex) are
used primarily as an adjunct for rest in management
of acute muscle spasms associated with sprains. Muscle
relaxation may also be an adjunct to physical therapy
in rehabilitation following stroke, spinal cord injury,
or other musculoskeletal conditions.
Diazepam and methocarbamol are also used by
injection for relief of tetanus.

Mupirocin see Antibiotics, topical
Murine (endemic) typhus see Typhus
Muscle cramps see Muscle spasms and
cramps

Muscle relaxants
Definition
Skeletal muscle relaxants are drugs that relax
striated muscles (those that control the skeleton).
2516

Recommended dosage
Dose varies with the drug, route of administration,
and purpose. There may be individual variations in
absorption that require doses higher than those usually
recommended, particularly with methocarbamol.
Consult specific references for further information.

Precautions
All drugs in this class may cause sedation.
Baclofen, when administered intrathecally, may
cause severe central nervous system (CNS) depression
with cardiovascular collapse and respiratory failure.
GALE ENCYCLOPEDIA OF MEDICINE

Dantrolene has a potential for hepatotoxicity.
The incidence of symptomatic hepatitis is dose related,
but may occur even with a short period of doses at or
above. Even short periods of doses at or above 800 mg
per day greatly increases the risk of serious liver injury.
Overt hepatitis has been most frequently observed
between the third and twelfth months of therapy.
Risk of hepatic injury appears to be greater in
women, in patients over 35 years of age and in patients
taking other medications in addition to dantrolene.
Tizanidine may cause low blood pressure, but this
may be controlled by starting with a low dose and
increasing it gradually. The drug may rarely cause
liver damage.
Methocarbamol and chlorzoxazone may cause
harmless color changes in urine—orange or reddishpurple with chlorzoxazone and purple, brown, or
green with methocarbamol. The urine will return to
its normal color when the patient stops taking the
medicine.
Most drugs in this class are well tolerated.
Not all drugs in this group have been evaluated
for safety in pregnancy and breast feeding.
Baclofen is pregnancy category C. It has caused
fetal abnormalities in rats at doses 13 times above the
human dose. Baclofen passes into breast milk, and
breast feeding while taking baclofen is not
recommended.
Diazepam is category D. All benzodiazepines cross
the placenta. Although the drugs appear to be safe for
use during the first trimester of pregnancy, use later in
pregnancy may be associated with cleft lip and palate.
Diazepam should not be taken while breast feeding.
Infants who were breast fed while their mothers took
diazepam were excessively sleepy and lethargic.
Dantrolene is category C. In animal studies it has
reduced the rate of survival of the newborn when given
in doses seven times the normal human dose. Mothers
should not breast feed while receiving dantrolene.

KEY TERMS
Central nervous system—The brain and spinal
cord.
Intrathecal—Introduced into or occurring in the
space under the arachnoid membrane which
covers the brain and spinal cord.
Pregnancy category— A system of classifying drugs
according to their established risks for use during
pregnancy. Category A: Controlled human studies
have demonstrated no fetal risk. Category B:
Animal studies indicate no fetal risk, but no
human studies, or adverse effects in animals, but
not in well-controlled human studies. Category C:
No adequate human or animal studies, or adverse
fetal effects in animal studies, but no available
human data. Category D: Evidence of fetal risk,
but benefits outweigh risks. Category X: Evidence
of fetal risk. Risks outweigh any benefits.
Sedative—Medicine used to treat nervousness or
restlessness.
Spasm—Sudden, involuntary tensing of a muscle or
a group of muscles.
Tranquilizer (minor)—A drug that has a calming
effect and is used to treat anxiety and emotional
tension.

The activity of diazepam may be increased by
drugs that inhibit its metabolism in the liver. These
include: Cimetidine, oral contraceptives, Disulfiram,
Fluoxetine, Isoniazid, Ketoconazole, Metoprolol,
Propoxyphene, Propranolol, and Valproic acid.
Dantrolene may have an interaction with estrogens. Although no interaction has been demonstrated,
the rate of liver damage in women over the age of 35
who were taking estrogens is higher than in other
groups.
Samuel D. Uretsky, PharmD

Interactions
Skeletal muscle relaxants have many potential
drug interactions. Individual references should be
consulted.
Because these drugs cause sedation, they should
be used with caution with other drugs that may also
cause drowsiness.
GALE ENCYCLOPEDIA OF MEDICINE

Muscle spasms and cramps
Definition
Muscle spasms and cramps are spontaneous,
often painful muscle contractions.
2517

Muscle spasms and cramps

Diazepam may be addictive. It is a controlled
substance under federal law.

Muscle spasms and cramps

Description
Most people are familiar with the sudden pain of a
muscle cramp. The rapid, uncontrolled contraction, or
spasm, happens unexpectedly, with either no stimulation or some trivially small one. The muscle contraction and pain last for several minutes, and then slowly
ease. Cramps may affect any muscle, but are most
common in the calves, feet, and hands. While painful,
they are harmless, and in most cases, not related to any
underlying disorder. Nonetheless, cramps and spasms
can be manifestations of many neurological or muscular diseases.

Interuption of brain mechanisms and overly
sensitive motor neurons may result from damage to
the nerve pathways. Possible causes include stroke,
multiple sclerosis, cerebral palsy, neurodegenerative
diseases, trauma, spinal cord injury, and nervous
system poisons such as strychnine, tetanus, and certain insecticides. Nerve damage may lead to a prolonged or permanent muscle shortening called
contracture.
Changes in muscle responsiveness may be due to
or associated with:


Prolonged exercise. Curiously, relaxation of a muscle
actually requires energy to be expended. The energy
is used to recapture calcium and to unlink actin and
myosin. Normally, sensations of pain and fatigue
signal that it is time to rest. Ignoring or overriding
those warning signals can lead to such severe energy
depletion that the muscle cannot be relaxed, causing
a cramp. The familiar advice about not swimming
after a heavy meal, when blood flow is directed away
from the muscles, is intended to avoid this type of
cramp. Rigor mortis, the stiffness of a corpse within
the first 24 hours after death, is also due to this
phenomenon.



Dehydration and salt depletion. This may be brought
on by protracted vomiting or diarrhea, or by copious
sweating during prolonged exercise, especially in
high temperatures. Loss of fluids and salts—especially
sodium, potassium, magnesium, and calcium—can
disrupt ion balances in both muscle and nerves. This
can prevent them from responding and recovering
normally, and can lead to cramp.



Metabolic disorders that affect the energy supply in
muscle. These are inherited diseases in which particular muscle enzymes are deficient. They include deficiencies of myophosphorylase (McArdle’s disease),
phosphorylase b kinase, phosphofructokinase, phosphoglycerate kinase, and lactate dehydrogenase.



Myotonia. This causes stiffness due to delayed
relaxation of the muscle, but does not cause the
spontaneous contraction usually associated with
cramps. However, many patients with myotonia do
experience cramping from exercise. Symptoms of
myotonia are often worse in the cold. Myotonias
include myotonic dystrophy, myotonia congenita,
paramyotonia congenita, and neuromyotonia.

The terms cramp and spasm can be somewhat
vague, and they are sometimes used to include types
of abnormal muscle activity other than sudden painful
contraction. These include stiffness at rest, slow muscle relaxation, and spontaneous contractions of a muscle at rest (fasciculation). Fasciculation is a type of
painless muscle spasm, marked by rapid, uncoordinated contraction of many small muscle fibers. A
critical part of diagnosis is to distinguish these different meanings and to allow the patient to describe the
problem as precisely as possible.

Causes and symptoms
Causes
Normal voluntary muscle contraction begins
when electrical signals are sent from the brain through
the spinal cord along nerve cells called motor neurons.
These include both the upper motor neurons within
the brain and the lower motor neurons within the
spinal cord and leading out to the muscle. At the
muscle, chemicals released by the motor neuron stimulate the internal release of calcium ions from stores
within the muscle cell. These calcium ions then interact
with muscle proteins within the cell, causing the proteins (actin and myosin) to slide past one another. This
motion pulls their fixed ends closer, thereby shortening the cell and, ultimately, the muscle itself.
Recapture of calcium and unlinking of actin and myosin allows the muscle fiber to relax.
Abnormal contraction may be caused by abnormal activity at any stage in this process. Certain
mechanisms within the brain and the rest of the central
nervous
system
help
regulate
contraction.
Interruption of these mechanisms can cause spasm.
Motor neurons that are overly sensitive may fire
below their normal thresholds. The muscle membrane
itself may be over sensitive, causing contraction without stimulation. Calcium ions may not be recaptured
quickly enough, causing prolonged contraction.
2518

Fasciculations may be due to fatigue, cold, medications, metabolic disorders, nerve damage, or neurodegenerative disease, including amyotrophic lateral
sclerosis. Most people experience brief, mild fasciculations from time to time, usually in the calves.
GALE ENCYCLOPEDIA OF MEDICINE

Motor neuron—Nerve cells within the central nervous system that carry nerve impulses controlling
muscle movement.

Symptoms
The pain of a muscle cramp is intense, localized,
and often debilitating Coming on quickly, it may last
for minutes and fade gradually. Contractures develop
more slowly, over days or weeks, and may be permanent if untreated. Fasciculations may occur at rest or
after muscle contraction, and may last several
minutes.

The likelihood of developing cramps may be
reduced by eating a healthy diet with appropriate
levels of minerals, and getting regular exercise to
build up energy reserves in muscle. Avoiding exercising in extreme heat helps prevent heat cramps. Heat
cramps can also be avoided by taking salt tablets and
water before prolonged exercise in extreme heat.
Taking a warm bath before bedtime may increase
circulation to the legs and reduce the incidence of
nighttime leg cramps.
Resources
BOOKS

Bradley, Walter G., et al. Neurology in Clinical Practice. 2nd
ed. Woburn, MA: Butterworth-Heinemann, 1995.

Richard Robinson

Diagnosis
Abnormal contractions are diagnosed through a
careful medical history, physical and neurological
examination, and electromyography of the affected
muscles. Electromyography records electrical activity
in the muscle during rest and movement.

Treatment
Most cases of simple cramps require no treatment
other than patience and stretching. Gently and gradually stretching and massaging the affected muscle may
ease the pain and hasten recovery.
More prolonged or regular cramps may be treated
with drugs such as carbamazepine, phenytoin, or quinine. Fluid and salt replacement, either orally or intravenously, is used to treat dehydration. Treatment of
underlying metabolic or neurologic disease, where
possible, may help relieve symptoms.

Muscular dystrophy
Definition
Muscular dystrophy is the name for a group of
inherited disorders in which strength and muscle bulk
gradually decline. Nine types of muscular dystrophies
are generally recognized.

Description
The muscular dystrophies include:


Duchenne muscular dystrophy (DMD): DMD
affects young boys, causing progressive muscle
weakness, usually beginning in the legs. It is the
most severe form of muscular dystrophy. DMD
occurs in about 1 in 3,500 male births, and affects
approximately 8,000 boys and young men in the
United States. A milder form occurs in very few
female carriers.



Becker muscular dystrophy (BMD): BMD affects
older boys and young men, following a milder course
than DMD. BMD occurs in about 1 in 30,000 male
births.



Emery-Dreifuss muscular dystrophy (EDMD):
EDMD affects young boys, causing contractures
and weakness in the calves, weakness in the shoulders
and upper arms, and problems in the way electrical
impulses travel through the heart to make it beat

Alternative treatment
Cramps may be treated or prevented with
Gingko (Ginkgo biloba) or Japanese quince
(Chaenomeles speciosa). Supplements of vitamin E,
niacin, calcium, and magnesium may also help.
Taken at bedtime, they may help to reduce the likelihood of night cramps.

Prognosis
Occasional cramps are common, and have no
special medical significance.
GALE ENCYCLOPEDIA OF MEDICINE

2519

Muscular dystrophy

Prevention

KEY TERMS

Muscular dystrophy

(heart conduction defects). Fewer than 300 cases of
EDMD have been identified.


Limb-girdle muscular dystrophy (LGMD): LGMD
begins in late childhood to early adulthood and
affects both men and women, causing weakness in
the muscles around the hips and shoulders. It is the
most variable of the muscular dystrophies, and there
are several different forms of the disease now recognized. Many people with suspected LGMD have
probably been misdiagnosed in the past, and therefore the prevalence of the disease is difficult to estimate. The number of people affected in the United
States may be in the low thousands.



Facioscapulohumeral muscular dystrophy (FSH):
FSH, also known as Landouzy-Dejerine disease,
begins in late childhood to early adulthood and
affects both men and women, causing weakness in
the muscles of the face, shoulders, and upper arms.
The hips and legs may also be affected. FSH occurs
in about 1 out of every 20,000 people, and affects
approximately 13,000 people in the United States.



Myotonic dystrophy: also known as Steinert’s disease, affects both men and women, causing generalized weakness first seen in the face, feet, and hands. It
is accompanied by the inability to relax the affected
muscles (myotonia). Symptoms may begin from
birth through adulthood. It is the most common
form of muscular dystrophy, affecting more than
30,000 people in the United States.



Oculopharyngeal muscular dystrophy (OPMD):
OPMD affects adults of both sexes, causing weakness in the eye muscles and throat. It is most common
among French Canadian families in Quebec, and in
Spanish-American families in the southwestern
United States.



Distal muscular dystrophy (DD): DD begins in middle age or later, causing weakness in the muscles of
the feet and hands. It is most common in Sweden,
and rare in other parts of the world.



Congenital muscular dystrophy (CMD): CMD is
present from birth, results in generalized weakness,
and usually progresses slowly. A subtype, called
Fukuyama CMD, also involves mental retardation.
Both are rare; Fukuyama CMD is more common in
Japan.

Causes and symptoms
Causes
Several of the muscular dystrophies, including
DMD, BMD, CMD, and most forms of LGMD, are
2520

due to defects in the genes for a complex of muscle
proteins. This complex spans the muscle cell membrane to unite a fibrous network on the interior of
the cell with a fibrous network on the outside.
Current theory holds that by linking these two networks, the complex acts as a ‘‘shock absorber,’’ redistributing and evening out the forces generated by
contraction of the muscle, thereby preventing rupture
of the muscle membrane. Defects in the proteins of the
complex lead to deterioration of the muscle.
Symptoms of these diseases set in as the muscle gradually exhausts its ability to repair itself. Both DMD
and BMD are caused by flaws in the gene for the
protein called dystrophin. The flaw leading to DMD
prevents the formation of any dystrophin, while that
of BMD allows some protein to be made, accounting
for the differences in severity and onset between the
two diseases. Differences among the other diseases in
the muscles involved and the ages of onset are less
easily explained.
The causes of the other muscular dystrophies are
not as well understood:


One form of LGMD is caused by defects in the gene
for a muscle enzyme, calpain. The relationship
between this defect and the symptoms of the disease
is unclear.



EDMD is due to a defect in the gene for a protein
called emerin, which is found in the membrane of a
cell’s nucleus, but whose exact function is unknown.



Myotonic dystrophy is linked to gene defects for a
protein that may control the flow of charged particles within muscle cells. This gene defect is called a
triple repeat, meaning it contains extra triplets of
DNA code. It is possible that this mutation affects
nearby genes as well, and that the widespread symptoms of myotonic dystrophy are due to a range of
genetic disruptions.



The gene for OPMD appears to also be mutated with
a triple repeat. The function of the affected protein
may involve translation of genetic messages in a cell’s
nucleus.



The cause of FSH is unknown. Although the genetic
region responsible for it has been localized on its
chromosome, the identity and function of the gene
or genes involved had not been determined as of
1997.



The gene responsible for DD has not yet been found.
Genetics and patterns of inheritance

The muscular dystrophies are genetic diseases,
meaning they are caused by defects in genes. Genes,
GALE ENCYCLOPEDIA OF MEDICINE

Because both parents contribute genetic material
to their offspring, each child carries two copies of
almost every gene, one from each parent. For some
diseases to occur, both copies must be flawed. Such
diseases are called autosomal recessive diseases. Some
forms of LGMD and DD exhibit this pattern of
inheritance, as does CMD. A person with only one
flawed copy, called a carrier, will not have the disease,
but may pass the flawed gene on to his children. When
two carriers have children, the chances of having a
child with the disease is one in four for each pregnancy.
Other diseases occur when only one flawed gene
copy is present. Such diseases are called autosomal
dominant diseases. Other forms of LGMD exhibit
this pattern of inheritance, as do DM, FSH, OPMD,
and some forms of DD. When a person affected by the
disease has a child with someone not affected, the
chances of having an affected child is one in two.
Because of chromosomal differences between the
sexes, some genes are not present in two copies. The
chromosomes that determine whether a person is male
or female are called the X and Y chromosomes. A
person with two X chromosomes is female, while a
person with one X and one Y is male. While the X
chromosome carries many genes, the Y chromosome
carries almost none. Therefore, a male has only one
copy of each gene on the X chromosome, and if it is
flawed, he will have the disease that defect causes. Such
diseases are said to be X-linked. X-linked diseases
include DMD, BMD, and EDMD. Women aren’t
usually affected by X-linked diseases, since they will
likely have one unaffected copy between the two chromosomes. Some female carriers of DMD suffer a mild
form of the disease, probably because their one unaffected gene copy is shut down in some of their cells.
Women carriers of X-linked diseases have a one in
two chance of passing the flawed gene on to each child
born. Daughters who inherit the disease gene will be
carriers. A son born without the disease gene will be
free of the disease and cannot pass it on to his children.
A son born with the defect will have the disease. He
will pass the flawed gene on to each of his daughters,
who will then be carriers, but to none of his sons
(because they inherit his Y chromosome).
Not all genetic flaws are inherited. As many as one
third of the cases of DMD are due to new mutations
GALE ENCYCLOPEDIA OF MEDICINE

that arise during egg formation in the mother. New
mutations are less common in other forms of muscular
dystrophy.
Symptoms
All of the muscular dystrophies are marked by
muscle weakness as the major symptom. The distribution of symptoms, age of onset, and progression differ
significantly. Pain is sometimes a symptom of each,
usually due to the effects of weakness on joint
position.
DMD. A boy with Duchenne muscular dystrophy
usually begins to show symptoms as a pre-schooler.
The legs are affected first, making walking difficult
and causing balance problems. Most patients walk
three to six months later than expected and have difficulty running. Later on, the boy with DMD will push
his hands against his knees to rise to a standing position, to compensate for leg weakness. About the same
time, his calves will begin to swell, though with fibrous
tissue rather than with muscle, and feel firm and rubbery; this condition gives DMD one of its alternate
names, pseudohypertrophic muscular dystrophy. He
will widen his stance to maintain balance, and walk
with a waddling gait to advance his weakened legs.
Contractures (permanent muscle tightening) usually
begin by age five or six, most severely in the calf
muscles. This pulls the foot down and back, forcing
the boy to walk on tip-toes, called equinus, and further
decreases balance. Frequent falls and broken bones
are common beginning at this age. Climbing stairs
and rising unaided may become impossible by age
nine or ten, and most boys use a wheelchair for mobility by the age of 12. Weakening of the trunk muscles
around this age often leads to scoliosis (a side-to-side
spine curvature) and kyphosis (a front-to-back
curvature).

The most serious weakness of DMD is weakness
of the diaphragm, the sheet of muscles at the top of the
abdomen that perform the main work of breathing
and coughing. Diaphragm weakness leads to reduced
energy and stamina, and increased lung infection
because of the inability to cough effectively. Young
men with DMD often live into their twenties and
beyond, provided they have mechanical ventilation
assistance and good respiratory hygiene.
About one third of boys with DMD experience
specific learning disabilities, including trouble learning by ear rather than by sight and trouble paying
attention to long lists of instructions. Individualized
educational programs usually compensate well for
these disabilities.
2521

Muscular dystrophy

which are linked together on chromosomes, have two
functions: They code for the production of proteins,
and they are the material of inheritance. Parents pass
along genes to their children, providing them with a
complete set of instructions for making their own
proteins.

Muscular dystrophy

BMD. The symptoms of BMD usually appear in
late childhood to early adulthood. Though the progression of symptoms may parallel that of DMD, the
symptoms are usually milder and the course more
variable. The same pattern of leg weakness, unsteadiness, and contractures occur later for the young man
with BMD, often allowing independent walking into
the twenties or early thirties. Scoliosis may occur, but
is usually milder and progresses more slowly. Heart
muscle disease (cardiomyopathy), occurs more commonly in BMD. Problems may include irregular heartbeats (arrhythmias) and congestive heart failure.
Symptoms may include fatigue, shortness of breath,
chest pain, and dizziness. Respiratory weakness also
occurs, and may lead to the need for mechanical
ventilation.
EDMD. This type of muscular dystrophy usually
begins in early childhood, often with contractures preceding muscle weakness. Weakness affects the
shoulder and upper arm originally, along with the
calf muscles, leading to foot-drop. Most men with
EDMD survive into middle age, although a defect in
the heart’s rhythm (heart block) may be fatal if not
treated with a pacemaker.
LGMD. While there are at least a half-dozen genes
that cause the various types of LGMD, two major
clinical forms of LGMD are usually recognized. A
severe childhood form is similar in appearance to
DMD, but is inherited as an autosomal recessive trait.
Symptoms of adult-onset LGMD usually appear in a
person’s teens or twenties, and are marked by progressive weakness and wasting of the muscles closest to the
trunk. Contractures may occur, and the ability to walk
is usually lost about 20 years after onset. Some people
with LGMD develop respiratory weakness that requires
use of a ventilator. Lifespan may be somewhat shortened. (Autosomal dominant forms usually occur later
in life and progress relatively slowly.)
FSH. FSH varies in its severity and age of onset,

even among members of the same family. Symptoms
most commonly begin in the teens or early twenties,
though infant or childhood onset is possible.
Symptoms tend to be more severe in those with earlier
onset. The disease is named for the regions of the body
most severely affected by the disease: muscles of the
face (facio-), shoulders (scapulo-), and upper arms
(humeral). Hips and legs may be affected as well.
Children with FSH often develop partial or complete
deafness.
The first symptom noticed is often difficulty lifting objects above the shoulders. The weakness may be
greater on one side than the other. Shoulder weakness
2522

also causes the shoulder blades to jut backward, called
scapular winging. Muscles in the upper arm often lose
bulk sooner than those of the forearm, giving a
‘‘Popeye’’ appearance to the arms. Facial weakness
may lead to loss of facial expression, difficulty closing
the eyes completely, and inability to drink through a
straw, blow up a balloon, or whistle. A person with
FSH may not develop strong facial wrinkles.
Contracture of the calf muscles may cause foot-drop,
leading to frequent tripping over curbs or rough spots.
People with earlier onset often require a wheelchair for
mobility, while those with later onset rarely do.
MYOTONIC DYSTROPHY. Symptoms of Myotonic
dystrophy include facial weakness and a slack jaw,
drooping eyelids (ptosis), and muscle wasting in the
forearms and calves. A person with this dystrophy has
difficulty relaxing his grasp, especially if the object is
cold. Myotonic dystrophy affects heart muscle, causing arrhythmias and heart block, and the muscles of
the digestive system, leading to motility disorders and
constipation. Other body systems are affected as well:
Myotonic dystrophy may cause cataracts, retinal
degeneration, low IQ, frontal balding, skin disorders,
testicular atrophy, sleep apnea, and insulin resistance.
An increased need or desire for sleep is common, as is
diminished motivation. Severe disability affects most
people with this type of dystrophy within 20 years of
onset, although most do not require a wheelchair even
late in life.
OPMD. OPMD usually begins in a person’s thirties or forties, with weakness in the muscles controlling
the eyes and throat. Symptoms include drooping eyelids, difficulty swallowing (dysphagia), and weakness
progresses to other muscles of the face, neck, and
occasionally the upper limbs. Swallowing difficulty
may cause aspiration, or the introduction of food or
saliva into the airways. Pneumonia may follow.
DD. DD usually begins in the twenties or thirties,
with weakness in the hands, forearms, and lower legs.
Difficulty with fine movements such as typing or fastening buttons may be the first symptoms. Symptoms
progress slowly, and the disease usually does not affect
life span.
CMD. CMD is marked by severe muscle weakness
from birth, with infants displaying ‘‘floppiness’’ and
very little voluntary movement. Nonetheless, a child
with CMD may learn to walk, either with or without
some assistive device, and live into young adulthood
or beyond. In contrast, children with Fukuyama
CMD are rarely able to walk, and have severe mental
retardation. Most children with this type of CMD die
in childhood.

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis of muscular dystrophy involves a careful medical history and a thorough physical exam to
determine the distribution of symptoms and to rule
out other causes. Family history may give important
clues, since all the muscular dystrophies are genetic
conditions (though no family history will be evident in
the event of new mutations).
Lab tests may include:


Blood level of the muscle enzyme creatine kinase
(CK). CK levels rise in the blood due to muscle
damage, and may be seen in some conditions even
before symptoms appear.



Muscle biopsy, in which a small piece of muscle
tissue is removed for microscopic examination.
Changes in the structure of muscle cells and presence
of fibrous tissue or other aberrant structures are
characteristic of different forms of muscular dystrophy. The muscle tissue can also be stained to detect
the presence or absence of particular proteins,
including dystrophin.



Electromyogram (EMG). This electrical test is used
to examine the response of the muscles to stimulation. Decreased response is seen in muscular dystrophy. Other characteristic changes are seen in DM.



Genetic tests. Several of the muscular dystrophies
can be positively identified by testing for the presence
of the mutated gene involved. Accurate genetic tests
are available for DMD, BMD, DM, several forms of
LGMD, and EDMD.



Other specific tests as necessary. For EDMD and
BMD, for example, an electrocardiogram may be
needed to test heart function, and hearing tests are
performed for children with FSH.

For most forms of muscular dystrophy, accurate
diagnosis is not difficult when done by someone
familiar with the range of diseases. There are exceptions, however. Even with a muscle biopsy, it may be
difficult to distinguish between FSH and another
muscle disease, polymyositis. Childhood-onset
LGMD is often mistaken for the much more common
DMD, especially when it occurs in boys. BMD with
an early onset appears very similar to DMD, and a
genetic test may be needed to accurately distinguish
them. The muscular dystrophies may be confused
with diseases involving the motor neurons, such as
spinal muscular atrophy; diseases of the neuromuscular junction, such as myasthenia gravis; and other
muscle diseases, as all involve generalized weakening
of varying distribution.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Drugs
There are no cures for any of the muscular dystrophies. Prednisone, a corticosteroid, has been shown to
delay the progression of DMD somewhat, for reasons
that are still unclear. Prednisone is also prescribed for
BMD, though no controlled studies have tested its
benefit. A related drug, deflazacort, appears to have
similar benefits with fewer side effects. It is available
and is prescribed in Canada and Mexico, but is unavailable in the United States. Albuterol, an adrenergic
agonist, has shown some promise for FSH in small
trials; larger trials are scheduled for 1998. No other
drugs are currently known to have an effect on the
course of any other muscular dystrophy.
Treatment of muscular dystrophy is mainly directed at preventing the complications of weakness, including decreased mobility and dexterity, contractures,
scoliosis, heart defects, and respiratory insufficiency.
Physical therapy
Physical therapy, in particular regular stretching,
is used to maintain the range of motion of affected
muscles and to prevent or delay contractures. Braces
are used as well, especially on the ankles and feet to
prevent equinus. Full-leg braces may be used in DMD
to prolong the period of independent walking.
Strengthening other muscle groups to compensate
for weakness may be possible if the affected muscles
are few and isolated, as in the earlier stages of the
milder muscular dystrophies. Regular, nonstrenuous
exercise helps maintain general good health.
Strenuous exercise is usually not recommended, since
it may damage muscles further.
Surgery
When contractures become more pronounced,
tenotomy surgery may be performed. In this operation,
the tendon of the contractured muscle is cut, and the
limb is braced in its normal resting position while the
tendon regrows. In FSH, surgical fixation of the scapula
can help compensate for shoulder weakness. For a person with OPMD, surgical lifting of the eyelids may help
compensate for weakened muscular control. For a person with DM, sleep apnea may be treated surgically to
maintain an open airway. Scoliosis surgery is often
needed in DMD, but much less often in other muscular
dystrophies. Surgery is recommended at a much lower
degree of curvature for DMD than for scoliosis due to
other conditions, since the decline in respiratory function in DMD makes surgery at a later time dangerous.
2523

Muscular dystrophy

Diagnosis

Muscular dystrophy

In this surgery, the vertebrae are fused together to maintain the spine in the upright position. Steel rods are
inserted at the time of operation to keep the spine rigid
while the bones grow together.
When any type of surgery is performed in patients
with muscular dystrophy, anesthesia must be carefully
selected. People with MD are susceptible to a severe
reaction, known as malignant hyperthermia, when
given halothane anesthetic.
Occupational therapy
The occupational therapist suggests techniques
and tools to compensate for the loss of strength and
dexterity. Strategies may include modifications in the
home, adaptive utensils and dressing aids, compensatory movements and positioning, wheelchair accessories, or communication aids.
Nutrition
Good nutrition helps to promote general health in
all the muscular dystrophies. No special diet or supplement has been shown to be of use in any of the
conditions. The weakness in the throat muscles seen
especially in OPMD and later DMD may necessitate
the use of a gastrostomy tube, inserted in the stomach
to provide nutrition directly.
Cardiac care
The arrhythmias of EDMD and BMD may be
treatable with antiarrhythmia drugs such as mexiletine
or nifedipine. A pacemaker may be implanted if these
do not provide adequate control. Heart transplants
are increasingly common for men with BMD.
Respiratory care
People who develop weakness of the diaphragm
or other ventilatory muscles may require a mechanical
ventilator to continue breathing deeply enough. Air
may be administered through a nasal mask or mouthpiece, or through a tracheostomy tube, which is
inserted through a surgical incision through the neck
and into the windpipe. Most people with muscular
dystrophy do not need a tracheostomy, although
some may prefer it to continual use of a mask or
mouthpiece. Supplemental oxygen is not needed.
Good hygiene of the lungs is critical for health and
longterm survival of a person with weakened ventilatory muscles. Assisted cough techniques provide the
strength needed to clear the airways of secretions; an
assisted cough machine is also available and provides
excellent results.
2524

Experimental treatments
Two experimental procedures aiming to cure
DMD have attracted a great deal of attention in the
past decade. In myoblast transfer, millions of immature muscle cells are injected into an affected muscle.
The goal of the treatment is to promote the growth of
the injected cells, replacing the defective host cells with
healthy new ones. Despite continued claims to the
contrary by a very few researchers, this procedure is
widely judged a failure. Modifications in the technique
may change that in the future.
Gene therapy introduces good copies of the dystrophin gene into muscle cells. The goal is to allow the
existing muscle cells to use the new gene to produce the
dystrophin it cannot make with its flawed gene.
Problems have included immune rejection of the
virus used to introduce the gene, loss of gene function
after several weeks, and an inability to get the gene to
enough cells to make a functional difference in the
affected muscle. Nonetheless, after a number of years
of refining the techniques in mice, researchers are
beginning human trials in 1998.

Prognosis
The expected lifespan for a male with DMD has
increased significantly in the past two decades. Most
young men will live into their early or mid-twenties.
Respiratory infections become an increasing problem
as their breathing becomes weaker, and these infections are usually the cause of death.
The course of the other muscular dystrophies is
more variable; expected life spans and degrees of disability are hard to predict, but may be related to age of
onset and initial symptoms. Prediction is made more
difficult because, as new genes are discovered, it is
becoming clear that several of the dystrophies are not
uniform disorders, but rather symptom groups caused
by different genes.
People with dystrophies with significant heart
involvement (BMD, EDMD, Myotonic dystrophy)
may nonetheless have almost normal life spans, provided that cardiac complications are monitored and
treated aggressively. The respiratory involvement of
BMD and LGMD similarly require careful and
prompt treatment.

Prevention
There is no way to prevent any of the muscular
dystrophies in a person who has the genes responsible
for these disorders. Accurate genetic tests, including
GALE ENCYCLOPEDIA OF MEDICINE

prenatal tests, are available for some of the muscular
dystrophies. Results of these tests may be useful for
purposes of family planning.

Autosomal dominant—Diseases that occur when
a person inherits only one flawed copy of the
gene.

Resources

Autosomal recessive —Diseases that occur when a
person inherits two flawed copies of a gene—one
from each parent.

Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson, AZ 85718. (800) 572-1717. <http://
www.mdausa.org>.

Becker muscular dystrophy (BMD)—A type of
muscular dystrophy that affects older boys and
men, and usually follows a milder course than
DMD.

Richard Robinson

Contractures—A permanent shortening (as of muscle, tendon, or scar tissue) producing deformity or
distortion.
Distal muscular dystrophy (DD)—A form of muscular dystrophy that usually begins in middle age or
later, causing weakness in the muscles of the feet
and hands.
Duchenne muscular dystrophy (DMD)—The most
severe form of muscular dystrophy, DMD usually
affects young boys and causes progressive muscle
weakness, usually beginning in the legs.
Dystrophin—A protein that helps muscle tissue
repair itself. Both DMD and BMD are caused by
flaws in the gene that instructs the body how to
make this protein.
Facioscapulohumeral muscular dystrophy (FSH)—
This form of muscular dystrophy, also known as
Landouzy-Dejerine disease, begins in late childhood to early adulthood and affects both men and
women, causing weakness in the muscles of the
face, shoulders, and upper arms.
Limb-girdle muscular dystrophy (LGMD)—This
form of muscular dystrophy begins in late childhood to early adulthood and affects both men and
women, causing weakness in the muscles around
the hips and shoulders.
Myotonic dystrophy—This type of muscular dystrophy, also known as Steinert’s disease, affects
both men and women, causing generalized weakness first seen in the face, feet, and hands. It is
accompanied by the inability to relax the affected
muscles (myotonia).
Oculopharyngeal muscular dystrophy (OPMD)—
This type of muscular dystrophy affects adults of
both sexes, causing weakness in the eye muscles
and throat.

GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

Mushroom poisoning
Definition
Mushroom poisoning refers to the severe and often
deadly effects of various toxins that are found in certain types of mushrooms. One type known as Amanita
phalloides, appropriately called ‘‘death cap,’’ accounts
for the majority of cases. The toxins initially cause
severe abdominal cramping, vomiting, and watery
diarrhea, and then lead to liver and kidney failure.

Description
The highest reported incidences of mushroom poisoning occur in western Europe, where a popular pastime is amateur mushroom hunting. Since the 1970s,
the United States has seen a marked increase in mushroom poisoning due to an increase in the popularity of
‘‘natural’’ foods, the use of mushrooms as recreational
hallucinogens, and the gourmet qualities of wild
mushrooms. About 90% of the deaths due to mushroom poisoning in the United States and western
Europe result from eating Amanita phalloides. This
mushroom is recognized by its metallic green cap
(the color may vary from light yellow to greenish
brown), white gills (located under the cap), white
stem, and bulb-shaped structure at the base of the
stem. A pure white variety of this species also occurs.
Poisoning results from ingestion of as few as one to
three mushrooms. Higher death (mortality) rates of
more than 50% occur in children less than 10 years
of age.

Causes and symptoms
Poisonous mushrooms contain at least two different types of toxins, each of which can cause death if
taken in large enough quantities. Some of the toxins
2525

Mushroom poisoning

KEY TERMS

Mushroom poisoning

found in poisonous mushrooms are among the most
potent ever discovered. One group of poisons, known
as amatoxins, blocks the production of DNA, the
basis of cell reproduction. This leads to the death of
many cells, especially those that reproduce frequently
such as in the liver, intestines, and kidney. Other
mushroom poisons affect the proteins needed for muscle contraction, and therefore reduce the ability of
certain muscle groups to perform.
Symptoms of Amanita poisoning occur in different stages or phases. These include:


First phase. Abdominal cramping, nausea, vomiting,
and severe watery diarrhea occur anywhere from 624 hours after eating the mushroom and last for
about 24 hours. These intestinal symptoms can lead
to dehydration and low blood pressure
(hypotension).



Second phase. A period of remission of symptoms
that lasts 1-2 days. During this time, the patient feels
better, but blood tests begin to show evidence of liver
and kidney damage.



Third phase. Liver and kidney failure develop at this
point and either lead to death within about a week or
recovery within 2-3 weeks.

Other symptoms are due to either a decrease in
blood clotting factors that leads to internal bleeding or
reduced muscle function, with the development of
weakness and paralysis.

Diagnosis
In most cases, the fact that the patient has recently
eaten wild mushrooms is the clue to the cause of symptoms. Moreover, the identification of any remaining
mushrooms by a qualified mushroom specialist (mycologist) can be a key to diagnosis. When in doubt, the
toxin known as alpha-amantin can be found in the
blood, urine, or stomach contents of an individual
who has ingested poisonous Amanita mushrooms.

Treatment
It is important to remember that there is no specific antidote for mushroom poisoning. However, several advances in therapy have decreased the death rate
over the last several years. Early replacement of lost
body fluids has been a major factor in improving
survival rates.
Therapy is aimed at decreasing the amount of
toxin in the body. Initially, attempts are made to
remove toxins from the upper gastrointestinal tract
by inducing vomiting or by gastric lavage (stomach
2526

A poisonous mushroom, Amanita muscaria (Photo
Researchers. Reproduced by permission.)

pumping). After that continuous aspiration of the
upper portion of the small intestine through a nasogastric tube is done and oral charcoal (every four
hours for 48 hours) is given to prevent absorption of
toxin. These measures work best if started within six
hours of ingestion.
In the United States, early removal of mushroom
poison by way of an artificial kidney machine (dialysis) has become part of the treatment program. This
is combined with the correction of any imbalances of
salts (electrolytes) dissolved in the blood, such as
sodium or potassium. An enzyme called thioctic
acid and corticosteroids also appear to be beneficial,
as well as high doses of penicillin. In Europe, a chemical taken from the milk thistle plant, Silybum marianum , is also part of treatment. When liver failure
develops, liver transplantation may be the only treatment option.

Prognosis
The mortality rate has decreased with improved
and rapid treatment. However, according to some
medical reports death still occurs in 20-30% of cases,
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
The most important factor in preventing mushroom poisoning is to avoid eating wild or noncultivated mushrooms. For anyone not expert in
mushroom identification, there are generally no easily
recognizable differences between nonpoisonous and
poisonous mushrooms. It is also important to remember that most mushroom poisons are not destroyed or
deactivated by cooking, canning, freezing, drying, or
other means of food preparation.
Resources
OTHER

‘‘Alerts from the CDC.’’ Experience Lab Page. <http://
www.medsitenavigator.com>.
‘‘Cyclopeptide-Containing Mushroom Toxicity.’’ The
Toxikon Multimedia Project Page. <http://www
.uic.edu/com/er/toxikon/mushroo.htm>.
‘‘Mushroom Poisoning in Children.’’ American Association
of Family Physicians. <http://www.aafp.org/patientinfo/mushroom.html>.
Mushroom Toxins from the FDA. <http://vm.cfsan.fda.gov/~mow/chap40.html>.

David Kaminstein, MD

There are no potentially harmful or toxic effects.
Music therapists help their patients achieve a number
of goals through music, including improvement of
communication, academic strengths, attention span,
and motor skills. They may also assist with behavioral
therapy and pain management.
Physical effects
Brain function physically changes in response to
music. The rhythm can guide the body into breathing
in slower, deeper patterns that have a calming effect.
Heart rate and blood pressure are also responsive to
the types of music that are listened to. The speed of the
heartbeat tends to speed or slow depending on the
volume and speed of the auditory stimulus. Louder
and faster noises tend to raise both heart rate and
blood pressure; slower, softer, and more regular
tones produce the opposite result. Music can also
relieve muscle tension and improve motor skills. It is
often used to help rebuild physical patterning skills in
rehabilitation clinics. Levels of endorphins, natural
pain relievers, are increased while listening to music,
and levels of stress hormones are decreased. This latter
effect may partially explain the ability of music to
improve immune function. A 1993 study at Michigan
State University showed that even 15 minutes of exposure to music could increase interleukin-1 levels, a
consequence which also heightens immunity.
Mental effects

Music therapy
Definition
Music therapy is a technique of complementary
medicine that uses music prescribed in a skilled manner
by trained therapists. Programs are designed to help
patients overcome physical, emotional, intellectual, and
social challenges. Applications range from improving the
well being of geriatric patients in nursing homes to lowering the stress level and pain of women in labor. Music
therapy is used in many settings, including schools, rehabilitation centers, hospitals, hospice, nursing homes,
community centers, and sometimes even in the home.

Purpose
Music can be beneficial for anyone. Although it
can be used therapeutically for people who have physical, emotional, social, or cognitive deficits, even
those who are healthy can use music to relax, reduce
stress, improve mood, or to accompany exercise.
GALE ENCYCLOPEDIA OF MEDICINE

Depending on the type and style of sound, music
can either sharpen mental acuity or assist in relaxation. Memory and learning can be enhanced, and this
used with good results in children with learning disabilities. This effect may also be partially due to
increased concentration that many people have while
listening to music. Better productivity is another outcome of an improved ability to concentrate. The term
‘‘Mozart effect’’ was coined after a study showed that
college students performed better on math problems
when listening to classical music.
Emotional effects
The ability of music to influence human emotion
is well known, and is used extensively by moviemakers. A variety of musical moods may be used to
create feelings of calmness, tension, excitement, or
romance. Lullabies have long been popular for soothing babies to sleep. Music can also be used to express
emotion nonverbally, which can be a very valuable
therapeutic tool in some settings.
2527

Music therapy

with a higher mortality rate of 50% in children less
than 10 years old.

Music therapy

Description
Origins
Music has been used throughout human history to
express and affect human emotion. In biblical
accounts, King Saul was reportedly soothed by
David’s harp music, and the ancient Greeks expressed
thoughts about music having healing effects as well.
Many cultures are steeped in musical traditions. It can
change mood, have stimulant or sedative effects, and
alter physiologic processes such as heart rate and
breathing. The apparent health benefits of music to
patients in Veterans Administration hospitals following World War II lead to it being studied and formalized as a complementary healing practice. Musicians
were hired to continue working in the hospitals.
Degrees in music therapy became available in the late
1940s, and in 1950, the first professional association of
music therapists was formed in the United States. The
National Association of Music Therapy merged with
the American Association of Music Therapy in 1998
to become the American Music Therapy Association.
Goals
Music is used to form a relationship with the
patient. The music therapist sets goals on an individual basis, depending on the reasons for treatment,
and selects specific activities and exercises to help the
patient progress. Objectives may include development
of communication, cognitive, motor, emotional, and
social skills. Some of the techniques used to achieve
this are singing, listening, instrumental music, composition, creative movement, guided imagery, and other
methods as appropriate. Other disciplines may be integrated as well, such as dance, art, and psychology.
Patients may develop musical abilities as a result of
therapy, but this is not a major concern. The primary
aim is to improve the patient’s ability to function.
Techniques
Learning to play an instrument is an excellent
musical activity to develop motor skills in individuals
with developmental delays, brain injuries, or other
motor impairment. It is also an exercise in impulse
control and group cooperation. Creative movement
is another activity that can help to improve coordination, as well as strength, balance, and gait.
Improvisation facilitates the nonverbal expression of
emotion. It encourages socialization and communication about feelings as well. Singing develops articulation, rhythm, and breath control. Remembering lyrics
and melody is an exercise in sequencing for stroke
victims and others who may be intellectually impaired.
2528

Composition of words and music is one avenue available to assist the patient in working through fears and
negative feelings. Listening is an excellent way to practice attending and remembering. It may also make the
patient aware of memories and emotions that need to
be acknowledged and perhaps talked about. Singing
and discussion is a similar method, which is used with
some patient populations to encourage dialogue.
Guided Imagery and Music (GIM) is a very popular
technique developed by music therapist Helen Bonny.
Listening to music is used as a path to invoke emotions, picture, and symbols from the patient. This is a
bridge to the exploration and expression of feelings.
Music and children
The sensory stimulation and playful nature of
music can help to develop a child’s ability to express
emotion, communicate, and develop rhythmic movement. There is also some evidence to show that speech
and language skills can be improved through the stimulation of both hemispheres of the brain. Just as with
adults, appropriately selected music can decrease
stress, anxiety, and pain. Music therapy in a hospital
environment with those who are sick, preparing for
surgery, or recovering postoperatively is appropriate
and beneficial. Children can also experience improved
self-esteem through musical activities that allow them
to succeed.
Newborns may enjoy an even greater benefit of
music. Those who are premature experience more
rapid weight gain and hospital discharge than their
peers who are not exposed to music. There is also
anecdotal evidence of improved cognitive function.
Music and rehabilitation
Patients with brain damage from stroke, traumatic
brain injury, or other neurologic conditions have been
shown to exhibit significant improvement as a result of
music therapy. This is theorized to be partially the result
of entrainment, which is the synchronization of movement with the rhythm of the music. Consistent practice
leads to gains in motor skill ability and efficiency.
Cognitive processes and language skills often benefit
from appropriate musical intervention.
Music and the elderly
The geriatric population can be particularly prone
to anxiety and depression, particularly in nursing home
residents. Chronic diseases causing pain are also not
uncommon in this setting. Music is an excellent outlet
to provide enjoyment, relaxation, relief from pain, and
an opportunity to socialize and reminisce about music
GALE ENCYCLOPEDIA OF MEDICINE

Music and the mentally ill
Music can be an effective tool for the mentally or
emotionally ill. Autism is one disorder that has been
particularly researched. Music therapy has enabled
some autistic children to relate to others and have
improved learning skills. Substance abuse, schizophrenia, paranoia, and disorders of personality, anxiety, and
affect are all conditions that may be benefited by music
therapy. In these groups, participation and social interaction are promoted through music. Reality orientation
is improved. Patients are helped to develop coping
skills, reduce stress, and express their feelings.
Music and hospice
Pain, anxiety, and depression are major concerns
with patients who are terminally ill, whether they are
in hospice or not. Music can provide some relief from
pain, through release of endorphins and promotion of
relaxation. It can also provide an opportunity for the
patient to reminisce and talk about the fears that are
associated with death and dying. Music may help regulate the rapid breathing of a patient who is anxious,
and soothe the mind. The Chalice of Repose project,
headquartered at St. Patrick Hospital in Missoula,
Montana, is one organization that attends and nurtures dying patients through the use of music, in a
practice they called music-thanatology by developer
Therese Schroeder-Sheker. Practitioners in this program work to relieve suffering through music prescribed for the individual patient.

KEY TERMS
Entrainment—The patterning of body processes
and movements to the rhythm of music
Physiologic—Characteristic of normal, healthy
functioning

natural form of pain relief. Many women select different styles of music for each stage of labor, with a more
intense, or faster piece feeling like a natural accompaniment to the more difficult parts of labor.
Instrumental music is often preferred.

Precautions
Patients making use of music therapy should not
discontinue medications or therapies prescribed by
other health providers without prior consultation.

Research and general acceptance
There is little disagreement among physicians that
music can be of some benefit for patients, although the
extent to which it can have physical effects is not as well
acknowledged in the medical community. Research has
shown that listening to music can decrease anxiety,
pain, and recovery time. There is also good data for
the specific subpopulations discussed. A therapist referral can be made through the AMTA.
Resources
ORGANIZATIONS

American Music Therapy Association, Inc. 8455 Colesville
Road, Suite 1000 Silver Spring, ML 20910. (301) 5893300. <http://www.musictherapy.org>.
Chalice of Repose Project at St. Patrick Hospital. 312 East
Pine Street, Missoula, MT 59802. (406) 329-2810. Fax:
(406) 329-5614. <http://www.saintpatrick.org/chalice/>.

Judith Turner

Music and labor
Research has proven that mothers require less
pharmaceutical pain relief during labor if they make
use of music. Using music that is familiar and associated with positive imagery is the most helpful.
During early labor, this will promote relaxation.
Maternal movement is helpful to get the baby into a
proper birthing position and dilate the cervix.
Enjoying some ‘‘music to move by’’ can encourage
the mother to stay active for as long as possible during
labor. The rhythmic auditory stimulation may also
prompt the body to release endorphins, which are a
GALE ENCYCLOPEDIA OF MEDICINE

Mutism

that has had special importance to the individual. It can
have a striking effect on patients with Alzheimer’s disease, even sometimes allowing them to focus and become
responsive for a time. Music has also been observed to
decrease the agitation that is so common with this disease. One study shows that elderly people who play a
musical instrument are more physically and emotionally
fit as they age than their nonmusical peers are.

Mutism
Definition
Mutism is a rare childhood condition characterized by a consistent failure to speak in situations where
talking is expected. The child has the ability to converse
2529

Myasthenia gravis

normally, and does so, for example, in the home, but
consistently fails to speak in specific situations such as
at school or with strangers. It is estimated that one in
every 1,000 school-age children are affected.

Description
Experts believe that this problem is associated
with anxiety and fear in social situations such as in
school or in the company of adults. It is therefore often
considered a type of social phobia. This is not a communication disorder because the affected children can
converse normally in some situations. It is not a developmental disorder because their ability to talk, when
they choose to do so, is appropriate for their age level.
This problem has been linked to anxiety, and one of
the major ways in which both children and adults
attempt to cope with anxiety is by avoiding whatever
provokes the anxiety.
Affected children are typically shy, and are especially so in the presence of strangers and unfamiliar
surroundings or situations. However, the behaviors of
children with this condition go beyond shyness.

KEY TERMS
Behavior modification—A form of therapy that
uses rewards to reinforce desired behavior. An
example would be to give a child a piece of chocolate for grooming themselves appropriately.

Prognosis
The prognosis for mutism is good. Sometimes it
disappears suddenly on its own. The negative impact
on learning and school activities may, however, persist
into adult life.

Prevention
Mutism cannot be prevented because the cause is
not known. However, family conflict or problems at
school contribute to the seriousness of the symptoms.
Resources
BOOKS

Causes and symptoms
Mutism is believed to arise from anxiety experienced in social situations where the child may be called
upon to speak. Refusing to speak, or speaking in a
whisper, spares the child from the possible humiliation
or embarrassment of ‘‘saying the wrong thing.’’ When
asked a direct question by teachers, for example, the
affected child may act as if they are unable to
answer. Some children may communicate via gestures,
nodding, or very brief utterances. Additional features
may include excessive shyness, oppositional behavior,
and impaired learning at school.

Diagnosis
The diagnosis of mutism is fairly easy to make
because the signs amd symptoms are clear-cut and
easily observable. However, other social disorders
effecting social speech, such as autism or schizophrenia, must be considered in the diagnosis.

Treatment
There are two recommended treatments for mutism: behavior modification therapy and antidepressant medication. Treatment is most effective when
individualized to each patient. It has been suggested
that speech pathologists may also be able to help these
children.
2530

Diagnostic and Statistical Manual of Mental Disorders. 4th
ed. Washington, DC: American Psychiatric
Association, 1994.

Donald G. Barstow, RN

MVP see Mitral valve prolapse

Myasthenia gravis
Definition
Myasthenia gravis is an autoimmune disease that
causes muscle weakness.

Description
Myasthenia gravis (MG) affects the neuromuscular junction, interrupting the communication
between nerve and muscle, and thereby causing
weakness. A person with MG may have difficulty
moving their eyes, walking, speaking clearly, swallowing, and even breathing, depending on the severity and distribution of weakness. Increased weakness
with exertion, and improvement with rest, is a characteristic feature of MG.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Myasthenia gravis is an autoimmune disease,
meaning it is caused by the body’s own immune system. In MG, the immune system attacks a receptor on
the surface of muscle cells. This prevents the muscle
from receiving the nerve impulses that normally make
it respond. MG affects ‘‘voluntary’’ muscles, which
are those muscles under conscious control responsible
for movement. It does not affect heart muscle or the
‘‘smooth’’ muscle found in the digestive system and
other internal organs.
A muscle is stimulated to contract when the nerve
cell controlling it releases acetylcholine molecules onto
its surface. The acetylcholine lands on a muscle protein called the acetylcholine receptor. This leads to
rapid chemical changes in the muscle which cause it
to contract. Acetylcholine is then broken down by
acetylcholinesterase enzyme, to prevent further
stimulation.
In MG, immune cells create antibodies against the
acetylcholine receptor. Antibodies are proteins normally involved in fighting infection. When these antibodies attach to the receptor, they prevent it from
receiving acetylcholine, decreasing the ability of the
muscle to respond to stimulation.
Why the immune system creates these self-reactive
‘‘autoantibodies’’ is unknown, although there are several hypotheses:


During fetal development, the immune system generates many B cells that can make autoantibodies,
but B cells that could harm the body’s own tissues are
screened out and destroyed before birth. It is possible
that the stage is set for MG when some of these cells
escape detection.



Genes controlling other parts of the immune system,
called MHC genes, appear to influence how susceptible a person is to developing autoimmune disease.



Infection may trigger some cases of MG. When activated, the immune system may mistake portions of
the acetylcholine receptor for portions of an invading
virus, though no candidate virus has yet been identified conclusively.



About 10% of those with MG also have thymomas,
or benign tumors of the thymus gland. The thymus is
a principal organ of the immune system, and

GALE ENCYCLOPEDIA OF MEDICINE

researchers speculate that thymic irregularities are
involved in the progression of MG.
Some or all of these factors (developmental,
genetic, infectious, and thymic) may interact to create
the autoimmune reaction.
The earliest symptoms of MG often result from
weakness of the extraocular muscles, which control
eye movements. Symptoms involving the eye (ocular
symptoms) include double vision (diplopia), especially
when not gazing straight ahead, and difficulty raising
the eyelids (ptosis). A person with ptosis may need to
tilt their head back to see. Eye-related symptoms
remain the only symptoms for about 15% of MG
patients. Another common early symptom is difficulty
chewing and swallowing, due to weakness in the bulbar muscles, which are in the mouth and throat.
Choking becomes more likely, especially with food
that requires extensive chewing.
Weakness usually becomes more widespread
within several months of the first symptoms, reaching
their maximum within a year in two-thirds of patients.
Weakness may involve muscles of the arms, legs, neck,
trunk, and face, and affect the ability to lift objects,
walk, hold the head up, and speak.
Symptoms of MG become worse upon exertion,
and better with rest. Heat, including heat from the sun,
hot showers, and hot drinks, may increase weakness.
Infection and stress may worsen symptoms.
Symptoms may vary from day to day and month to
month, with intervals of no weakness interspersed
with a progressive decline in strength.
‘‘Myasthenic crisis’’ may occur, in which the
breathing muscles become too weak to provide adequate respiration. Symptoms include weak and shallow breathing, shortness of breath, pale or bluish skin
color, and a racing heart. Myasthenic crisis is an
emergency condition requiring immediate treatment.
In patients treated with anticholinesterase agents,
myasthenic crisis must be differentiated from cholinergic crisis related to overmedication.
Pregnancy worsens MG in about one third of
women, has no effect in one third, and improves symptoms in another third. About 12% of infants born to
women with MG have ‘‘neonatal myasthenia,’’ a temporary but potentially life-threatening condition. It is
caused by the transfer of maternal antibodies into the
fetal circulation just before birth. Symptoms include
weakness, floppiness, feeble cry, and difficulty feeding.
The infant may have difficulty breathing, requiring the
use of a ventilator. Neonatal myasthenia usually clears
up within a month.
2531

Myasthenia gravis

About 30,000 people in the United States are
affected by MG. It can occur at any age, but is most
common in women who are in their late teens and
early twenties, and in men in their sixties and seventies.

Myasthenia gravis

Diagnosis
Myasthenia gravis is often diagnosed accurately
by a careful medical history and a neuromuscular
exam, but several tests are used to confirm the diagnosis. Other conditions causing worsening of bulbar
and skeletal muscles must be considered, including
drug-induced myasthenia, thyroid disease, LambertEaton myasthenic syndrome, botulism, and inherited
muscular dystrophies.
MG causes characteristic changes in the electrical
responses of muscles that may be observed with an
electromyogram, which measures muscular response
to electrical stimulation. Repetitive nerve stimulation
leads to reduction in the height of the measured muscle
response, reflecting the muscle’s tendency to become
fatigued.
Blood tests may confirm the presence of the antibody to the acetylcholine receptor, though up to a
quarter of MG patients will not have detectable levels.
A chest x ray or chest computed tomography scan (CT
scan) may be performed to look for thymoma.

Treatment
While there is no cure for myasthenia gravis, there
are a number of treatments that effectively control
symptoms in most people.
Edrophonium (Tensilon) blocks the action of
acetylcholinesterase, prolonging the effect of acetylcholine and increasing strength. An injection of edrophonium rapidly leads to a marked improvement in
most people with MG. An alternate drug, neostigmine, may also be used.
Pyridostigmine (Mestinon) is usually the first drug
tried. Like edrophonium, pyridostigmine blocks acetylcholinesterase. It is longer-acting, taken by mouth, and
well-tolerated. Loss of responsiveness and disease progression combine to eventually make pyridostigmine
ineffective in tolerable doses in many patients.
Thymectomy, or removal of the thymus gland,
has increasingly become standard treatment for MG.
Up to 85% of people with MG improve after thymectomy, with complete remission eventually seen in about
30%. The improvement may take months or even
several years to fully develop. Thymectomy is not
usually recommended for children with MG, since
the thymus continues to play an important immune
role throughout childhood.
Immune-suppressing drugs are used to treat MG
if response to pyridostigmine and thymectomy are not
adequate. Drugs include corticosteroids such as
2532

prednisone, and the non-steroids azathioprine
(Imuran) and cyclosporine (Sandimmune).
Plasma exchange may be performed to treat
myasthenic crisis or to improve very weak patients
before thymectomy. In this procedure, blood plasma
is removed and replaced with purified plasma free of
autoantibodies. It can produce a temporary improvement in symptoms, but is too expensive for long-term
treatment. Another blood treatment, intravenous
immunoglobulin therapy, is also used for myasthenic
crisis. In this procedure, large quantities of purified
immune proteins (immunoglobulins) are injected. For
unknown reasons, this leads to symptomatic improvement in up to 85% of patients. It is also too expensive
for long-term treatment.
People with weakness of the bulbar muscles may
need to eat softer foods that are easier to chew and
swallow. In more severe cases, it may be necessary to
obtain nutrition through a feeding tube placed into the
stomach (gastrostomy tube).

Prognosis
Most people with MG can be treated successfully
enough to prevent their condition from becoming
debilitating. In some cases, however, symptoms may
worsen even with vigorous treatment, leading to generalized weakness and disability. MG rarely causes
early death except from myasthenic crisis.

Prevention
There is no known way to prevent myasthenia
gravis. Thymectomy improves symptoms significantly
in many patients, and relieves them entirely in some.
Avoiding heat can help minimize symptoms.
Some drugs should be avoided by people with MG
because they interfere with normal neuromuscular
function.
Drugs to be avoided or used with caution include:


Many types of antibiotics, including erythromycin,
streptomycin, and ampicillin



Some cardiovascular drugs, including Verapamil,
betaxolol, and propranolol



Some drugs used in psychiatric conditions, including
chlorpromazine, clozapine, and lithium.

Many other drugs may worsen symptoms as well,
so patients should check with the doctor who treats
their MG before taking any new drugs.
A Medic-Alert card or bracelet provides an
important source of information to emergency
GALE ENCYCLOPEDIA OF MEDICINE

Antibody—An immune protein normally used by
the body for combating infection and which is
made by B cells.
Autoantibody—An antibody that reacts against
part of the self.
Autoimmune disease—A disease caused by a reaction of the body’s immune system.
Bulbar muscles—Muscles that control chewing,
swallowing, and speaking.
Neuromuscular junction—The site at which nerve
impulses are transmitted to muscles.
Pyridostigmine bromide (Mestinon)—An anticholinesterase drug used in treating myasthenia gravis.
Tensilon test—A test for diagnosing myasthenia
gravis. Tensilon is injected into a vein and, if the
person has MG, their muscle strength will improve
for about five minutes.
Thymus gland—A small gland located just above
the heart, involved in immune system
development.

foot. The infection is characterized by an abnormal
tissue mass beneath the skin, formation of cavities
within the mass, and a fluid discharge. As the infection
progresses, it affects the muscles and bones; at this
advanced stage, disability may result.

Description
Although the bacteria and fungi that cause mycetoma are found in soil worldwide, the disease occurs
mainly in tropical areas in India, Africa, South
America, Central America, and southeast Asia.
Mycetoma is an uncommon disease, affecting an
unknown number of people annually.
There are more than 30 species of bacteria and
fungi that can cause mycetoma. Bacteria or fungi can
be introduced into the body through a relatively minor
skin wound. The disease advances slowly over months
or years, typically with minimal pain. When pain is
experienced, it is usually due to secondary infections
or bone involvement. Although it is rarely fatal, mycetoma causes deformities and potential disability at its
advanced stage.

Causes and symptoms
providers about the special situation of a person with
MG. They are available from health care providers.
Resources
ORGANIZATIONS

Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson, AZ 85718. (800) 572-1717. <http://
www.mdausa.org>.
Myasthenia Gravis Foundation of America. 222 S.
Riverside Plaza, Suite 1540, Chicago, IL 60606. (800)
541-5454. <http://www.med.unc.edu>.

Richard Robinson

Mycetoma
Definition
Mycetoma, or maduromycosis, is a slow-growing
bacterial or fungal infection focused in one area of the
body, usually the foot. For this reason—and because
the first medical reports were from doctors in Madura,
India—an alternate name for the disease is Madura
GALE ENCYCLOPEDIA OF MEDICINE

Owing to a wound, bacteria or fungi gain entry
into the skin. Approximately one month or more after
the injury, a nodule forms under the skin surface. The
nodule is painless, even as it increases in size over the
following months. Eventually, the nodule forms a
tumor, or mass of abnormal tissue. The tumor contains cavities—called sinuses—that discharge bloodor pus-tainted fluid. The fluid also contains tiny
grains, less than two thousandths of an inch in size.
The color of these grains depends on the type of bacteria or fungi causing the infection.
As the infection continues, surrounding tissue
becomes involved, with an accumulation of scarring
and loss of function. The infection can extend to the
bone, causing inflammation, pain, and severe damage.
Mycetoma may be complicated by secondary infections, in which new bacteria become established in
the area and cause an additional set of problems.

Diagnosis
The primary symptoms of a tumor, sinuses, and
grain-flecked discharge often provide enough information to diagnose mycetoma. In the early stages,
prior to sinus formation, diagnosis may be more difficult and a biopsy, or microscopic examination of the
tissue, may be necessary. If bone involvement is
2533

Mycetoma

KEY TERMS

Mycobacterial infections, atypical

Resources

KEY TERMS
Biopsy—A medical procedure in which a small
piece of tissue is surgically removed for microscopic examination.
Grains—Flecks of hardened material such as bacteria or fungi spores.
Nodule—A hardened area or knot sometimes associated with infection.
Secondary infection—Illness caused by new bacteria, viruses, or fungi becoming established in the
wake of an initial infection.
Sinuses—Cavities or hollow areas.
Tumor—A mass or clump of abnormal tissue, not
necessarily caused by a cancer.

suspected, the area is x rayed to determine the extent of
the damage. The species of bacteria or fungi at the root
of the infection is identified by staining the discharge
grains and inspecting them with a microscope.

Treatment
Combating mycetoma requires both surgery and
drug therapy. Surgery usually consists of removing
the tumor and a portion of the surrounding tissue. If
the infection is extensive, amputation is sometimes
necessary. Drug therapy is recommended in conjunction with surgery. The specific prescription depends
on the type of bacteria or fungi causing the disease.
Common medicines include antifungal drugs, such
as ketoconazole and antibiotics (streptomycin sulfate, amikacin, sulfamethoxazole, penicillin, and
rifampin).

Prognosis
Recovery from mycetoma may take months or
years, and the infection recurs after surgery in at
least 20% of cases. Drug therapy can reduce the
chances of a re-established infection. The extent of
deformity or disability depends on the severity of
infection; the more deeply entrenched the infection,
the greater the damage. By itself, mycetoma is rarely
fatal, but secondary infections can be fatal.

Prevention
Mycetoma is a rare condition that is not
contagious.
2534

PERIODICALS

McGinnis, Michael R. ‘‘Mycetoma.’’ Dermatologic Clinics
14, no. 1 (January 1996): 97.

Julia Barrett

Mycobacterial infections,
atypical
Definition
Atypical mycobacterial infections are infections
caused by several types of mycobacteria similar to
the germ that causes tuberculosis. These atypical
mycobacterial infections are a frequent complication
in patients with human immunodeficiency virus (HIV)
infection or AIDS.

Description
Mycobacteria are a group of rod-shaped bacteria
that cause several diseases, among them leprosy and
tuberculosis. For some time, scientists have known of
bacteria that are similar to Mycobacterium tuberculosis, the cause of tuberculosis, but that grow and act
differently. When tuberculosis was a much more widespread problem and microbiology was much less able
to tell the difference between similar microbes, these
atypical mycobacteria were ignored. Today, they have
been classified more precisely as members of the same
species and called atypical (or nontuberculosis)
mycobacteria.
Although the medical profession has known
about these atypical infections for a long time, they
were not considered a serious problem until the early
1980s. It was then that many of these atypical infections were noticed among homosexuals and intravenous drug users in New York City. These bacteria
rarely cause infection in humans other than those
with HIV or AIDS.

Causes and symptoms
Although there are more than a dozen species of
atypical mycobacteria, the two most common are
Mycobacterium kansasii and M. avium-intracellulare.
These microbes are found in many places in the environment: tap water, fresh and ocean water, milk, bird
droppings, soil, and house dust. The manner in which
GALE ENCYCLOPEDIA OF MEDICINE

M. avium-intracellulare (MAC or MAI) is a rare
cause of lung disease in otherwise healthy humans but
a frequent cause of infection among those whose resistance has been lowered by another disorder (opportunistic infection). According to some experts, MAC
infection is an almost inevitable complication of
HIV. The infection is caused by one of two similar
organisms, M. avium and M. intracellulare.
AIDS patients are almost always attacked by
these mycobacteria. Once inside the body, the atypical
mycobacterial organisms colonize and grow in the
lungs like tuberculosis. Because AIDS patients have
a poorly functioning immune system, the microbes
multiply because they aren’t stopped by the body’s
normal response to infection. Once they have colonized the lungs, the organisms enter the bloodstream
and spread throughout the body, affecting almost
every organ. These devastating infections can invade
the lymph nodes, liver, spleen, bone marrow, gastrointestinal tract, skin, and brain.
Symptoms include shortness of breath, fever, night
sweats, weight loss, appetite loss, fatigue, and progressively severe diarrhea, stomach pain, nausea and vomiting. If the infection spreads to the brain, the patient
may experience weakness, headaches, vision problems, and loss of balance.
MAC and M. kansasii sometimes cause lung infections in middle-aged and elderly people with chronic
lung conditions. MAC, M. kansasii, and M. scrofulaceum may cause inflammation of the lymph nodes in
otherwise healthy young children. M. fortuitum and
M. chelonae cause skin and wound infections and
abscesses after trauma or surgical procedures. M. marinum causes a nodular inflammation, usually on the
arms and legs. This infection is called ‘‘swimming pool
granuloma’’ because it is associated with swimming
pools, fish tanks, and other bodies of water. M. ulcerans infection causes chronic skin ulcerations, usually
on an arm or leg. Atypical mycobacteria infections can
also occur without causing any symptoms. In such
cases, a tuberculin skin test may be positive.

Diagnosis
The diagnosis is made from the patient’s symptoms and organisms grown in culture from the site of
infection. In cases of lung infection, a diagnostic
workup will include a chest x ray and tests on discharges from the respiratory passages (sputum).
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Culture—A test in which a sample of body fluid,
such as prostatic fluid, is placed on materials specially formulated to grow microorganisms. A culture is used to learn what type of bacterium is
causing infection.
Human immunodeficiency virus (HIV)—The virus
that causes AIDS.

Treatment
These nontypical mycobacteria are not easy to
treat in any patient and the problem is complicated
when the person has AIDS. Antibiotics are not particularly effective, although rifabutin (a cousin of the
anti-tuberculosis drug rifampin) and clofazimine (an
anti-leprosy drug) have helped some patients. It is also
possible to contain the infection to some degree by
combining different drugs, including ethionamide,
cycloserine, ethambutol, and streptomycin.

Prognosis
Because drug therapy is not easily effective, the
overwhelming infections caused by these mycobacteria in AIDS patients can be fatal.

Prevention
People with HIV infection can prevent or delay
the onset of MAC by taking disease-preventing drugs
such as rifabutin.
AIDS patients and persons with tissue damage,
such as skin wounds or pulmonary disease, can make
a number of lifestyle changes to help prevent MAC
infection. Since these mycobacteria are found in
most city water systems, in hospital water supplies,
and in bottled water, at-risk persons should boil
drinking water. Persons at risk should also avoid
raw foods, especially salads, root vegetables, and
unpasteurized milk or cheese. Fruits and vegetables
should be peeled and rinsed thoroughly.
Conventional cooking (baking, boiling or steaming)
destroys mycobacteria, which are killed at 1768F
(808C).
Finally, at-risk patients should avoid contact with
animals, especially birds and bird droppings. Pigeons
in particular can transmit MAC.
2535

Mycobacterial infections, atypical

these bacteria are transmitted is not completely understood. There is no evidence that they are transmitted
from person to person.

Mycoplasma infections

Resources

KEY TERMS

ORGANIZATIONS

National AIDS Treatment Advocacy Project. 580
Broadway, Ste. 403, New York, NY 10012. (888) 2662827. <http://www.natap.org>.

Community-acquired—Refers to an infectious disease that is passed among individuals who have
close contact with one another.

Carol A. Turkington

Mycobacterium leprae infection see Leprosy
Mycobacterium tuberculosis see
Tuberculosis

Another mycoplasma species, M. hominis, is common in the mucous membranes of the genital area
(including the cervix), and can cause infection in
both males and females. Its presence does not always
result in symptoms.

Diagnosis

Mycoplasma infections
Definition
Mycoplasma are the smallest of the free-living
organisms. (Unlike viruses, mycoplasma can reproduce outside of living cells.) Many species within the
genus Mycoplasma thrive as parasites in human, bird,
and animal hosts. Some species can cause disease in
humans.

Description
Mycoplasma are found most often on the surfaces
of mucous membranes. They can cause chronic
inflammatory diseases of the respiratory system, urogenital tract, and joints. The most common human
illnesses caused by mycoplasma are due to infection
with M. pneumoniae, which is responsible for 10-20%
of all pneumonias. This type of pneumonia is also
called atypical pneumonia, walking pneumonia, or
community-acquired pneumonia. Infection moves
easily among people in close contact because it is
spread primarily when infected droplets circulate in
the air (that is, become aerosolized), usually due to
coughing, spitting, or sneezing.

Causes and symptoms
Atypical pneumonias can affect otherwise healthy
people who have close contact with one another.
Pneumonia caused by M. pneumoniae may start out
with symptoms of an upper respiratory infection,
probably a sore throat progressing to a dry cough
within a few days. Gradually, fever, fatigue, muscle
aches, and a cough that produces thin sputum (spit
or phlegm) will emerge. Nonrespiratory symptoms
may occur too: abdominal pain, headache, and diarrhea; about 20% of patients may have ear pain.
2536

Usually, mycoplasma pneumonia will be identified after other common diagnoses are set aside. For
example, a type of antibiotic known as a beta-lactam
might be prescribed for a respiratory infection producing fever and cough. If symptoms do not improve in
3-5 days, the organism causing the disease is not a
typical one and not susceptible to these antibiotics. If
a Gram’s stain (a common test done on sputum) does
not indicate a gram-positive pathogen, the doctor will
suspect a gram-negative organism, such as mycoplasma. The actual underlying organism may not be
identified (it is not in almost 50% of cases of atypical
pneumonia). Although it is rare, a rash may appear
along with pneumonia symptoms.This should trigger
suspicion of mycoplasma pneumonia, even if laboratory tests are inconclusive.
Standard x rays may reveal a patchy material that
has entered the tissue; this can be evident for months.
Laboratory tests include cold agglutinins, complement fixation, culture, and enzyme immunoassay.
The presence of infection with M. pneumoniae would
be indicated by a fourfold rise in M. pneumoniae-specific antibody in serum, during the illness or convalescence. Highly sophisticated and specific polymerase
chain reaction methods (PCR) have been developed
for many respiratory pathogens, including M. pneumoniae. They are not readily available and are very
expensive.

Treatment
A 2-3 week course of certain antibiotics (erythromycin, azithromycin, clarithromycin, dirithromycin,
or doxycycline) is generally prescribed for atypical
pneumonia. This disease is infectious for weeks, even
after the patient starts antibiotics. A persistent cough
may linger for 6 weeks.
GALE ENCYCLOPEDIA OF MEDICINE

Mycoplasma pneumonia may be involved in the
onset of asthma in adults; other rare complications
include meningoencephalitis, Guillain-Barré syndrome, mononeuritis multiplex, myocarditis, or pericarditis. This may increase the risk of acute
arrhythmias leading to sudden cardiac death.
However, with proper treatment and rest, recovery
should be complete.

Prevention
At this time, there are no vaccines for mycoplasma
infection. It is difficult to control its spread, especially
in a group setting. The best measures are still the
simplest ones. Avoid exposure to people with respiratory infections whenever possible. A person who has a
respiratory infection should cover the face while
coughing or sneezing.
Resources

blood cells), fighting infection (white blood cells), and
controlling bleeding (platelets). Blood cells are formed
and stored in the bone marrow, which is the spongy
tissue inside large bones. Stem cells, or immature
blood cells, are stored in the bone marrow and have
the ability to develop into all three types of mature
blood cells. When the body needs a specific type of
blood cell, the bone marrow uses its stockpile of stem
cells to produce the kind of mature cells needed for
that particular situation.
In patients who have MDS, blood cells fail to
mature normally. In other words, the bone marrow is
unable to develop a normal amount of mature blood
cells, and is also not able to increase blood cell production when mature cells are needed. Sometimes, even
the cells that are produced do not function normally.
The marrow eventually becomes filled with the immature cells and there is not room for the normal cells to
grow and develop. MDS therefore causes a shortage of
functional blood cells.

BOOKS

Subtypes of MDS

Cassell, Gail H., Gregory G. Gray, and K. B. Waites.
‘‘Mycoplasma Infections.’’ In Harrison’s Principles of
Internal Medicine, edited by Anthony S. Fauci, et al.
New York: McGraw-Hill, 1997.

Jill S. Lasker

Mycoplasmal pneumonia see Mycoplasma
infections
Myelocytic leukemia, acute see Leukemias,
acute

MDS is divided into five different subtypes that
are classified according to the number and appearance
of blast cells in the bone marrow. It is important for
doctors to know the type of MDS a patient has,
because each subtype affects patients differently and
requires specific treatment. The International
Prognostic Scoring System (IPSS) can help the doctor
to determine the best treatment for an individual
patient. The subtypes are as follows:


Refractory anemia (RA). Bone marrow with less
than 5% blast cells and abnormal red blood cell
blasts



Refractory anemia with ring sideroblasts (RARS).
Bone marrow with less than 5% blasts and characteristic abnormalities in red blood cells



Refractory anemia with excess blasts (RAEB). Bone
marrow with 5-20% blast cells, and higher risk of
changing into acute leukemia over time



Refractory anemia with excess blasts in transformation (RAEBT). Bone marrow with 21-30% blast
cells. This form is most likely to change into acute
leukemia.



Chronic myelomonocytic leukemia (CMMoL).
Marrow with 5-20% blasts and excess monocytes (a
specific type of white blood cell).

Myelodysplastic syndrome
Definition
Myelodysplastic syndrome (MDS) is a disease
that is associated with decreased production of blood
cells. Blood cells are produced in the bone marrow,
and the blood cells of people with MDS do not mature
normally. There are three major types of blood cells —
red blood cells, white blood cells and platelets.
Patients with MDS can have decreased production of
one, two, or all three types of blood cells.

Description
Blood cells are used in the body for many different
and important functions, such as carrying oxygen (red
GALE ENCYCLOPEDIA OF MEDICINE

Approximately 15,000 new cases are diagnosed
annually in the United States. The average age at
diagnosis is 70. The most common types are RA and
2537

Myelodysplastic syndrome

Prognosis

Myelodysplastic syndrome

RARS. It is rare to have MDS before age 50. MDS is
slightly more common in males than in females.

Causes and symptoms
Causes
There is no clear cause for the majority of MDS
cases, which is referred to as primary or de novo myelodysplastic syndrome. In some cases, however, MDS
results from earlier cancer treatments such as radiation
and/or chemotherapy. This type of MDS is called secondary or treatment related MDS, is often seen 3 to 7 years
after the exposure, and usually occurs in younger people.
Other possible causative agents for MDS include
exposure to radiation, cigarette smoke or toxic chemicals such as benzene. Children with pre-existing chromosomal abnormalities such as Down syndrome have a
higher risk of developing MDS. MDS does not appear
to run in families, nor can it be spread to other
individuals.
Symptoms
MDS symptoms are related to the type of blood
cells that the body is lacking. The earliest symptoms
are usually due to anemia, which results from a shortage of mature red blood cells. Anemia causes patients
to feel tired and out of breath because there is a lack of
cells transporting oxygen throughout the body. MDS
may also lead to a shortage of white blood cells resulting in an increased likelihood of infections. Another
symptom of MDS is increased bleeding (e.g., blood in
stool, nose bleeds, increased bruises or bleeding gums)
which is due to low level of platelets. These symptoms
can occur in any combination, depending on a given
patient’s specific subtype of MDS.

Diagnosis
Blood tests
People who have MDS usually visit their primary
care doctor first, with symptoms of fatigue, and are
then referred to a hematologist (a physician who specializes in diseases of the blood). The diagnosis of
MDS requires a complete analysis of the patient’s
blood and bone marrow, which is done by the hematologist. A complete blood count (CBC) is done to
determine the number of each blood cell type within
the sample. Low numbers of red blood cells, white
blood cells, and or platelets are signs that a patient
has MDS. Numerous other medical problems such as
bleeding, nutritional deficiencies, or adverse reaction
to a medication can also cause low blood counts. The
2538

hematologist will investigate other causes for low
blood counts before assigning a diagnosis of MDS.
Blood cells in patients with MDS can also be abnormal when viewed under the microscope.
Bone marrow aspiration and biopsy
A bone marrow biopsy is required to confirm the
diagnosis of MDS and determine the correct MDS
subtype. This procedure involves a needle used to take
a sample of marrow from inside the bone. The area of
the skin where the needle is inserted is numbed and
sometimes the patient is also sedated. Patients may
experience some discomfort but the procedure is safe
and is over fairly quickly. Marrow samples are usually
taken from the back of the hip bone (iliac crest). A
sample of the marrow, known as an aspirate, and a
small piece of bone are both removed with the needle.
A hematologist or a pathologist (a specialist in
diagnosing diseases through cell examination) will
carefully examine the bone marrow sample through a
microscope. Microscopic examination allows the doctor to determine the number and type of blast cells
(immature cells) within the marrow in order to identify
the MDS subtype. Cells from the bone marrow are
also sent for cytogenetic testing, which analyzes the
cells’ chromosomes. Forty to seventy percent of MDS
patients have abnormal bone marrow chromosomes
as a result of the disease. The pattern of these abnormalities can be used to predict how a patient will
respond to a particular treatment. Thus, the full set
of information provided by a bone marrow biopsy and
CBC will ultimately allow the doctor to recommend
the most effective treatment plan.
International Prognostic Scoring System (IPSS)
for MDS
Once a diagnosis of MDS is established, the doctor will calculate the IPSS score for each individual
patient. The bone marrow blast percentage, chromosomal abnormalities and number of different blood
types that are reduced determine the score. A score
of 0 to 3.5 is assigned to each patient. Patients with
lower score have a better prognosis and usually should
not undertake treatment upon initial diagnosis.
Patients with a higher score have more aggressive disease and should consider more aggressive treatment.

Treatments
Supportive care
Treatment for MDS is tailored to the patient’s
age, general health, specific MDS subtype, and IPSS
GALE ENCYCLOPEDIA OF MEDICINE

Supportive care for the MDS patients commonly
includes red blood cell transfusions to relieve symptoms related to anemia. Red cell transfusions are relatively safe and the physician will review risks and
benefits with this approach. Transfusions of any type
only last a certain amount of time and therefore need
to be repeated at certain intervals. Platelet transfusions can also be a way to control excessive bleeding.
The doctor will decide with each individual patient
when it is appropriate to give a transfusion.
Antibiotics are used when needed to combat infections
that can occur more frequently in patients with low
white blood cell counts.
Bone marrow transplantation
Bone marrow transplantation (BMT) is a type of
treatment that attempts to provide MDS patients with
a cure. This strategy requires the patients to be in fairly
good health and are therefore more likely to be used in
younger patients. Bone marrow transplantation
(BMT) has been found to be a successful treatment
for MDS patients under the age of 50 (and some over
50 in good health). Following BMT, many patients are
able to achieve long-term, disease-free survival.
Unfortunately, most MDS patients cannot receive a
traditional bone marrow transplant because of older
age or because they do not have a suitable donor. Bone
marrow donors are usually siblings or are obtained
from the national bone marrow registry. ‘‘Mini’’-bone
marrow transplants use less intense chemotherapy,
and are currently being tested in older patients who
would otherwise not be candidates for traditional
bone marrow transplants.
Chemotherapy
Chemotherapy has been used to treat some MDS
patients; however, the disease often recurs after a period of time. This type of therapy uses cell-killing drugs
that may also damage healthy cells in the body. Most
chemotherapy drugs are associated with some side
effects. For these reasons, chemotherapy is generally
not used until the MDS becomes more aggressive or
the patient has a high IPSS score.
Growth factors
Growth factors are natural proteins that the body
normally uses to control blood production. These substances stimulate the patient’s bone marrow to
GALE ENCYCLOPEDIA OF MEDICINE

produce healthy blood cells. Growth factors that stimulate white cell production are G-CSF (also called
neupogen or filgrastim) and GMCSF (Leukine, sargramostim). In order to increase red cell production
another growth factor, erythropoietin (Procrit) is
used. These growth factors are safe with few side
effects and are available only in the injectable form.
The physician will decide if this treatment is appropriate for an individual patient.

Alternative treatment
There are no alternative therapies that have been
proven to successfully treat MDS. Some of the available alternative drugs can have adverse side effects and
therefore a physician should be informed if they are
being used.

Prognosis
The prognosis for MDS patients depends on the
subtype of their disease and the IPSS score. Patients
with RA, RARS or low IPSS score rarely develop
leukemia and may live with disease for some years.
The higher-risk patients including those with RAEB,
RAEBt, CMMoL or high IPSS scores progress more
rapidly, and require intensive therapy to control the
disease.
Managing MDS requires frequent doctor
appointments to monitor disease progression and to
evaluate the response to treatment. Fortunately for
many patients, recent advances in therapy have significantly enhanced their ability to cope with MDS.
Experimental drugs and a better understanding of the
disease are likely to improve the overall prognosis in
the future.

Prevention
MDS is usually impossible to prevent. Being careful about daily activities and avoiding the use of
aspirin-like products that thin the blood may prevent
secondary complications of MDS such as bruising and
bleeding. Practicing good hygiene and avoiding
crowds or people with infections can sometimes prevent infections. A well balanced diet is recommended
to increase overall energy.
Resources
BOOKS

Aguayo, Alvaro, Jorge Cortes, and Hagop Kantarjian.
‘‘Myelodysplastic Syndromes.’’ In Cancer
Management: A Multidisciplinary Approach, edited by
Richard Pazdur, et al., 4th ed. PRR, Inc, 2000.
2539

Myelodysplastic syndrome

score. Treatment varies for each patient, but most
treatment strategies are designed to control the symptoms of MDS. This approach is called supportive care
and aims to improve the patient’s quality of life.

Myelofibrosis

ORGANIZATIONS

Aplastic Anemia Foundation of America. P.O. Box 613,
Annapolis, MD 21404. (800) 747-2820. <http://
www.aplastic.org>.
Leukemia Society of America. 600 Third Avenue, New
York, NY 10016. (800) 955-4572. <http://
www.leukemia.org>.
Myelodysplastic Syndromes Foundation. 464 Main Street,
P.O. Box 477, Crosswicks, NJ 08515. (800) MDS-0839.
<http://www.mds-foundation.org>.

Andrea Ruskin, M.D.

reduced production of blood cells by the bone marrow, a condition called anemia results.
The abnormal stem cells can spread throughout
the body, settle in other organs, and form tumors that
produce more abnormal blood cells and fibrous tissue.
These tumors are most commonly found in the adrenals, kidneys, lymph nodes, breast, lungs, skin, bowel,
thymus, thyroid, prostate, and urinary tract.
Most patients with myelofibrosis are over 50 years
old; the average age at diagnosis is 65 years. However,
myelofibrosis can occur at any age. Myelofibrosis
occurs with equal frequency in women and men, but
in children it affects girls twice as often as it does boys.

Causes and symptoms

Myelofibrosis
Definition
Myelofibrosis is a rare disease of the bone marrow
in which collagen builds up fibrous scar tissue inside
the marrow cavity. This is caused by the uncontrolled
growth of a blood cell precursor, which results in the
accumulation of scar tissue in bone marrow.
Myelofibrosis goes by many names including idiopathic myelofibrosis, agnogenic myeloid metaplasia,
chronic myelosclerosis, aleukemic megakaryocytic
myelosis, and leukoerythroblastosis.

Description
Myelofibrosis can be associated with many other
conditions including breast cancer, prostate cancer,
Hodgkin’s disease, non-Hodgkin’s lymphoma, acute
myeloid leukemia, acute lymphocytic leukemia, hairy
cell leukemia, multiple myeloma, myeloproliferative
diseases, tuberculosis, Gaucher’s disease, and Paget’s
disease of bone. Myelofibrosis typically becomes progressively worse and can cause death.
In myelofibrosis, abnormal cells (hematopoietic
stem cells) grow out of control and begin to produce
both immature blood cells and excess scar (fibrous)
tissue. The fibrous tissue builds up (fibrosis) primarily
in the bone marrow, the place where blood cells are
produced. The fibrous tissue interferes with the production of normal blood cells. The outcome of this is
that the blood made by the bone marrow is of poor
quality. To compensate for this, blood cell production
occurs in other parts of the body (extramedullary
hematopoiesis), but most notably in the spleen and
liver. This causes enlargement of the spleen (splenomegaly) and the liver (hepatomegaly). Extramedullary
hematopoiesis is not effective and, combined with the
2540

Myelofibrosis is caused by an abnormality in a
single stem cell, which causes it to grow out of control.
Myelofibrosis tumors that have originated from a single cell are called monoclonal. The cause of the stem
cell abnormality is unknown. Persons who were
exposed to benzene or high doses of radiation have
developed myelofibrosis. There may be an association
between myelofibrosis and autoimmune diseases, such
as systemic lupus erythematosus and scleroderma, in
which the immune system treats certain molecules of
the body as foreign invaders.
Symptoms usually appear slowly over a long period of time. About one quarter of all patients with
myelofibrosis have no symptoms (asymptomatic). An
enlarged spleen discovered at an annual medical examination may be the first clue. Symptoms of myelofibrosis include:


fatigue



weight loss



paleness



fever



sweating



weakness



heart palpitations



shortness of breath



itchiness



feeling full after eating a small amount of food



stomach pain or discomfort



pain in the left shoulder or upper left portion of the
body



unexpected bleeding



bone pain, especially in the legs
GALE ENCYCLOPEDIA OF MEDICINE

Because symptoms are similar to other diseases
(mostly leukemias), myelofibrosis is not easy to diagnose. The doctor would use his or her hands to feel
(palpate) for enlargement of the spleen and liver.
Blood tests and urine tests would be performed. Bone
marrow aspiration and biopsy can help make a diagnosis, but they often fail because of the fibrosis. X-ray
imaging and magnetic resonance imaging (MRI) may
be performed.

Treatment
Many asymptomatic patients, if stable, do not
require treatment. There is no cure for myelofibrosis,
although bone marrow transplantation is curative in
some cases. Treatment is aimed at reducing symptoms
and improving quality of life.
Medications
Male hormones (androgens) can be used to treat
anemia but, in women, these drugs can cause the
development of male characteristics (e.g., hair
growth on the face and body). Glucocorticoid therapy is also an effective treatment of anemia and can
improve myelofibrosis in children. Nutrients that stimulate blood formation (hematinics), such as iron,
folic acid, and vitamin B12, may reduce anemia.
Cancer chemotherapy (usually hydroxyurea) can
decrease splenomegaly and hepatomegaly, reduce
symptoms of myelofibrosis, lessen anemia, and
sometimes reduce bone marrow fibrosis. The bone
marrow of myelofibrosis patients is often not strong
enough to withstand the harsh chemotherapy drugs,
so this treatment is not always an option. Interferonalpha has been shown to reduce spleen size, reduce
bone pain, and, in some cases, increase the number of
blood platelets (structures involved in blood
clotting).
Other treatments
In certain cases, the enlarged spleen may be
removed (splenectomy). Conditions that warrant splenectomy include spleen pain, the need for frequent
blood transfusion, very low levels of platelets (thrombocytopenia), and extreme pressure in the blood vessels
of the liver (portal hypertension).
Radiation therapy is used to treat splenomegaly,
spleen pain, bone pain, tumors in certain places such
as next to the spinal cord, and fluid accumulation
inside the abdomen (ascites). Patients who are not
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anemia—Low numbers of red blood cells in the
blood.
Benzene—A colorless volatile flammable toxic
liquid hydrocarbon used as a solvent and as a
motor fuel.
Biopsy—Surgical removal of tissue for microscopic
examination.
Fibrosis—Buildup of scar tissue.
Glucocorticoid therapy—Treatment using corticoids
that
are
anti-inflammatory
and
immunosuppressive.
Leukemia—Cancer of white blood cells.
Portal hypertension—Extreme pressure on the
blood vessels of the liver.
Stem cell—A cell that has the ability to become
many different specialized cells.

strong enough to undergo splenectomy are often treated with radiation therapy.
Bone marrow transplantation may be used to
treat some patients with myelofibrosis. This procedure
may be performed on patients who are less than 50
years old, have a poor life expectancy, and have a
brother or sister with blood-type similarities.
Patients with severe anemia may require blood
transfusions.

Prognosis
Similar to leukemias, myelofibrosis is progressive
and often requires therapy to control the disease.
Myelofibrosis can progress to acute lymphocytic leukemia or lymphoma. Although a number of factors to
predict the survival time have been proposed,
advanced age or severe anemia are consistently associated with a poor prognosis. The average survival rate
of patients diagnosed with myelofibrosis is five years.
Death is usually caused by infection, bleeding, complications of splenectomy, heart failure, or progression
to leukemia. Spontaneous remission is rare.

Prevention
Persons who have been exposed to radiation, benzene, or radioactive thorium dioxide (a chemical used
during certain diagnostic radiological procedures) are
at risk for myelofibrosis.
2541

Myelofibrosis

Diagnosis

Myelography

Resources
BOOKS

Lichtman, Marshall. ‘‘Idiopathic Myelofibrosis (Agnogenic
Myeloid Metaplasia).’’ In Williams Hematology, edited
by Ernest Beutler, et al. New York: McGraw Hill, 2001,
pp.1125-36.
Mavroudis, Dimitrios and John Barrett. ‘‘Myelofibrosis
(Agnogenic Myeloid Metaplasia).’’ In Bone Marrow
Failure Syndromes, edited by Neal Young.
Philadelphia: W.B. Saunders Company, 2000,
pp.122-34.
Peterson, Powers. ‘‘Myelofibrosis.’’ In Practical Diagnosis of
Hematologic Disorders, edited by Carl Kjeldsberg.
Chicago: ASCP Press, 2000, pp.477-9.

Belinda Rowland, Ph.D.
J. Ricker Polsdorfer, MD

Myelogram see Myelography

Myelography
Definition
Myelography is an x-ray examination of the spinal
canal. A contrast agent is injected through a needle
into the space around the spinal cord to display the
spinal cord, spinal canal, and nerve roots on an x ray.

Purpose
The purpose of a myelogram is to evaluate the
spinal cord and/or nerve roots for suspected compression. Pressure on these delicate structures causes pain
or other symptoms. A myelogram is performed when
precise detail about the spinal cord is needed to make a
definitive diagnosis. In most cases, myelography is
used after other studies, such as magnetic resonance
imaging (MRI) or a computed tomography scan (CT
scan), have not yielded enough information to be sure
of the disease process. Sometimes myelography followed by CT scan is an alternative for patients who
cannot have an MRI scan, because they have a pacemaker or other implanted metallic device.
A herniated or ruptured intervertebral disc, popularly known as a slipped disc, is one of the most
common causes for pressure on the spinal cord or
nerve roots. Discs are pads of fiber and cartilage that
contain rubbery tissue. They lie between the vertebrae,
or individual bones, which make up the spine. Discs
act as cushions, accommodating strains, shocks, and
position changes. A disc may rupture suddenly, due to
2542

injury, or a sudden straining with the spine in an
unnatural position. In other cases, the problem may
come on gradually as a result of progressive deterioration of the discs with aging. The lower back is the most
common area for this problem, but it sometimes
occurs in the neck, and rarely in the upper back. A
myelogram can help accurately locate the disc or discs
involved.
Myelography may be used when a tumor is suspected. Tumors can originate in the spinal cord, or in
tissues surrounding the cord. Cancers that have started
in other parts of the body may spread or metastasize in
the spine. It is important to precisely locate the mass
causing pressure, so effective treatment can be undertaken. Patients with known cancer who develop back
pain may require a myelogram for evaluation.
Other conditions that may be diagnosed using
myelography include arthritic bony growths, known
as spurs, narrowing of the spinal canal, called spinal
stenosis, or malformations of the spine.

Precautions
Patients who are unable to lie still or cooperate
with positioning should not have this examination.
Severe congenital spinal abnormalities may make the
examination technically difficult to carry out. Patients
with a history of severe allergic reaction to contrast
material (x-ray dye) should report this to their physician. Pretreatment with medications to minimize the
risk of severe reaction may be recommended.

Description
Myelograms can be performed in a hospital x-ray
department or in an outpatient radiology facility. The
patient lies on the x-ray table on his or her stomach.
The radiologist first looks at the spine under fluoroscopy, where the images appear on a monitor screen.
This is done to find the best location to position the
needle. The skin is cleaned, then numbed with local
anesthetic. The needle is inserted. Occasionally, a
small amount of cerebrospinal fluid, the clear fluid
which surrounds the spinal cord and brain, may be
withdrawn through the needle and sent for laboratory
studies. Then contrast material is injected. The contrast material (dye) is a liquid that shows up on x rays.
The x-ray table is tilted slowly. This allows the
contrast material to reach different levels in the spinal
canal. The flow is observed under fluoroscopy, then x
rays are taken with the table tilted at various angles. A
footrest and shoulder straps or supports will keep the
patient from sliding.
GALE ENCYCLOPEDIA OF MEDICINE

A myelogram takes approximately 30-60 minutes.
A CT scan adds about another hour to the examination. If the procedure is done as an outpatient exam,
some facilities prefer the patient to stay in a recovery
area for up to four hours.

Preparation
Patients should be well hydrated at the time of a
myelogram. Increasing fluids the day before the study
is usually recommended. All food and fluid intake
should be stopped approximately four hours before
the myelogram.
Certain medications may need to be stopped for
one to two days before myelography is performed.
These include some antipsychotics, antidepressants,
blood thinners, and diabetic medications. Patients
should consult with their physician and/or the facility
where the study is to be done.
Patients who smoke may be asked to stop the day
before the test. This helps decrease the chance of nausea or headaches after the myelogram. Immediately
before the examination, patients should empty their
bowels and bladder.

Aftercare
After the examination is completed, the patient
usually rests for several hours, with the head elevated.
Extra fluids are encouraged, to help eliminate the contrast material and prevent headaches. A regular diet and
routine medications may be resumed. Strenuous physical activity, especially any which involve bending over,
may be discouraged for one or two days. The doctor
should be notified if a fever, excessive nausea and vomiting, severe headache, or stiff neck develops.

Risks
Headache is a common complication of myelography. It may begin several hours to several days after
the examination. The cause is thought to be changes in
cerebrospinal fluid pressure, not a reaction to the dye.
The headache may be mild and easily alleviated with
rest and increased fluids. Sometimes, nonprescription
medicine are recommended. In some instances, the
headache may be more severe and require stronger
medication or other measures for relief. Many factors
influence whether the patient develops this problem.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Contrast agent—Also called a contrast medium,
this is usually a barium or iodine dye that is injected
into the area under investigation. The dye makes
the interior body parts more visible on an x-ray film.

These include the type of needle used and the age and
sex of the patient. Patients with a history of chronic or
recurrent headache are more likely to develop a headache after a myelogram.
The chance of reaction to the contrast material is a
very small, but potentially significant risk with myelography. It is estimated that only 5-10% of patients
experience any effect from contrast exposure. The
vast majority of reactions are mild, such as sneezing,
nausea, or anxiety. These usually resolve by themselves. A moderate reaction, like wheezing or hives,
may be treated with medication, but is not considered
life threatening. Severe reactions, such as heart or
respiratory failure, happen very infrequently. These
require emergency medical treatment.
Rare complications of myelography include
injury to the nerve roots from the needle, or from
bleeding into the spaces around the roots.
Inflammation of the delicate covering of the spinal
cord, called arachnoiditis, or infections, can also
occur. Seizures are another very uncommon complication reported after myelography.

Normal results
A normal myelogram would show a spinal canal
of normal width, with no areas of constriction or
obstruction.

Abnormal results
A myelogram may reveal a herniated disk, tumor,
bone spurs, or narrowing of the spinal canal (spinal
stenosis).
Resources
ORGANIZATIONS

Spine Center. 1911 Arch St., Philadelphia, PA 19103. (215)
665-8300. <http://www.thespinecenter.com>.

Ellen S. Weber, MSN

Myeloma see Multiple myeloma
2543

Myelography

In many instances, a CT scan of the spine will be
performed immediately after a myelogram, while the
contrast material is still in the spinal canal. This helps
outline internal structures most clearly.

Myers-Briggs type indicator

Myers-Briggs type indicator
Definition
The Myers-Briggs Type Indicator (MBTI) is a
widely-used personality inventory, or test, employed
in vocational, educational, and psychotherapy settings
to evaluate personality type in adolescents and adults
age 14 and older.

Purpose
In an educational setting, the MBTI may be performed to assess student learning style. Career counselors use the test to help others determine what
occupational field they might be best suited for, and it
is also used in organizational settings to assess management skills and facilitate teamwork and problem-solving,
including communication difficulties. Because the MBTI
is also a tool for self-discovery, mental health professionals may administer the test in counseling sessions to
provide their patients with insight into their behavior.
As of the early 2000s, the MBTI is also being used
in the mental health field to assess vulnerability to
anxiety disorders and depression. Preliminary results
indicate that some of the 16 types are more susceptible
to mood disorders than others. ISFPs, for example, are
overrepresented among patients in treatment for unipolar depression, while the four ST types appear to be
more vulnerable to anxiety states.

beings are either introverts or extraverts, and their behavior follows from these inborn psychological types. He
also believed that people take in and process information different ways, based on their personality traits.
The Myers-Briggs evaluates personality type and
preference based on the four Jungian psychological
types:


extraversion (E) or introversion (I)



sensing (S) or intuition (N)



thinking (T) or feeling (F)



judging (J) or perceiving (P)

Preparation
Prior to the administration of the MBTI, the test
subject should be fully informed about the nature of the
test and its intended use. He or she should also receive
standardized instructions for taking the test and any
information on the confidentiality of the results.

Normal results
Myers-Briggs results are reported as a four-letter
personality type (e.g., ESTP, ISFJ). Each letter
corresponds to an individual’s preference in each of the
four pairs of personality indicators (i.e., E or I, S or N, T
or F, and J or P). There are a total of sixteen possible
combinations of personality types on the MBTI.
Letter One: E or I

Precautions
The MBTI should be administered, scored, and
interpreted only by a professional trained in its use.
Cultural and language differences in the test subject
may affect performance and may result in inaccurate
test results. The test administrator should be informed
before testing begins if the test taker is not fluent in
English and/or he has a unique cultural background.

Description
In 2000, an estimated two million people took the
MBTI, making it the most frequently used personality
inventory available. The test was first introduced in
1942, the work of a mother and daughter, Katharine
Cook Briggs and Isabel Briggs Myers. There are now
several different versions of the test available. Form M,
which contains 93 items, is the most commonly used.
The Myers-Briggs inventory is based on Carl
Jung’s theory of types, outlined in his 1921 work
Psychological Types. Jung’s theory holds that human
2544

Extraverts focus more on people and things in the
outside world, introverts on internal thoughts and
ideas.
Letter Two: S or N
Sensing dominant personalities prefer to perceive
things through sight, sound, taste, touch, and smell,
while intuition dominant types look to past experience
and are more abstract in their thinking.
Letter Three: T or F
The third subtype is a measure of how people use
judgment. Thinking types use logic to judge the world,
while feeling types tend to view things on the basis of
what emotions they elicit.
Letter Four: J or P
Everyone judges and perceives, but those who are
judging dominant are said to be more methodical and
GALE ENCYCLOPEDIA OF MEDICINE

Multitasking—Performing multiple duties or taking
on multiple responsibilities and roles simultaneously.
Vocational—Relating to an occupation, career,
or job.

This procedure is not used when the patient is
taking blood-thinning medication (anticoagulant
therapy). It should not be done when the patient has
leukemia and aplastic anemia or if there is a blood clot
on the interior wall of the heart.

Description
results-oriented, while perceiving dominant personalities are good at multitasking and are flexible.
Resources
BOOKS

Quenck, Naomi. Essentials of Myers-Briggs Type Indicator
Assessment. New York: John Wiley & Sons, 1999.

A long, flexible tube, called a catheter, is inserted
into a vein and threaded up into the heart. The doctor
can guide the catheter by watching its movement on a
TV monitor showing an x-ray image of the area. The
tip of the catheter is fitted with tiny jaws that the
doctor can open and close. Once the catheter is in
place, the doctor will take several small snips of muscle
for microscopic examination.

PERIODICALS

Clack, G. B., J. Allen, D. Cooper, and J. O. Head.
‘‘Personality Differences between Doctors and Their
Patients: Implications for the Teaching of
Communication Skills.’’ Medical Education 38
(February 2004): 177–186.
Janowsky, D. S., E. Hong, S. Morter, and L. Howe. ‘‘Myers
Briggs Type Indicator Personality Profiles in Unipolar
Depressed Patients.’’ World Journal of Biological
Psychiatry 3 (October 2002): 207–215.
Kameda, D. M., and J. L. Nyland. ‘‘Relationship between
Psychological Type and Sensitivity to Anxiety.’’
Perceptual and Motor Skills 97 (December 2003):
789–793.

Paula Anne Ford-Martin
Rebecca J. Frey, PhD

Preparation
Preparation for myocardial biopsy is quite extensive. The patient will be asked not to eat for several
hours before the procedure. A technician will shave
the hair from the area of the incision and will also
insert an intravenous line in the arm. The patient will
be given a sedative to relax but will not be fully
anesthetized. The patient will be connected to an
electrocardiograph (ECG) to monitor the heart, and
a blood-pressure cuff will be placed. Finally, the
patient will be covered with sterile drapes, so that
the area of the biopsy is kept free of germs. The
cardiologist will numb the area where the catheter
will be inserted.

Aftercare

Myocardial biopsy
Definition
Myocardial biopsy is a procedure wherein a small
portion of tissue is removed from the heart muscle for
testing. This test is also known as endomyocardial
biopsy.

At the end of the biopsy, the catheter will be
removed and pressure will be applied at the site
where it entered the blood vessel in order to encourage
healing. The patient will then be taken to the recovery
room. It is advisable to remain flat and not to move
about for 6-8 hours. After that time, most people begin
walking around. Swelling and bruising at the puncture
site are common and usually go away without need for
further attention.

Risks
Purpose
The main reason for a biopsy is to secure tissue
samples that will be useful in the diagnosis, treatment,
and care of heart muscle disorders. The test is also
used to detect rejection after a heart transplantation
procedure.
GALE ENCYCLOPEDIA OF MEDICINE

The risks involved with myocardial biopsy are
small because the patient is monitored closely and
attended by well-trained staff. Racing of the heart
(palpitations) and quivering of the heart muscles
(atrial fibrillation) are both possible during the
procedure.
2545

Myocardial biopsy

Precautions

KEY TERMS

Myocardial resection

KEY TERMS
Anticoagulant—Medication that thins the blood
and slows clot formation.
Aplastic anemia—A greatly decreased production
of all of the formed elements of the blood caused by
a failure of the cell-generating capacity of the bone
marrow.
Electrocardiography—A test that uses electrodes
attached to the chest with an adhesive gel to transmit the electrical impulses of the heart muscle to a
recording device.
Leukemia—A disease characterized by an increasing number of abnormal cells in the blood.

Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dorothy Elinor Stonely

Myocardial infarction see Heart attack

Once the catheter is threaded up into the heart, the surgeon
will take several small samples of muscle for laboratory analysis. (Custom Medical Stock Photo. Reproduced by permission.)

use of an implantable cardioverter-defibrillator (a
device that delivers electrical shock to control heart
rhythm) has been ruled out.

Description

Myocardial resection
Definition
Myocardial resection is a surgical procedure in
which a portion of the heart muscle is removed.

Purpose
Myocardial resection is done to improve the stability of the heart function or rhythm. Also known as
endocardial resection, this open-heart surgery is done
to destroy or remove damaged areas of the heart that
cause life-threatening heart rhythms. This procedure is
often performed in people who have had a heart attack,
in order to prevent future rapid heart rates. It is also
used in people who have Wolff-Parkinson-White syndrome (a condition resulting in abnormal heart rhythm).

Precautions
This is major surgery and should be the treatment
of choice only after medications have failed and the
2546

After receiving a general anesthetic, an incision
will be made in the chest to expose the heart. When
the exact source of the abnormal rhythm is identified,
it is removed. If there are areas around the source that
may contribute to the problem, they can be frozen
with a special probe to further insure against dangerous heart rates. The amount of tissue removed is so
small, usually only 2 or 3 millimeters, that there is no
damage to the structure of the heart. On some occasions, aneurysms of the heart wall are removed as well.

Preparation
Prior to surgery, the physician will explain the
procedure, routine blood tests will be completed, and
consent forms will be signed.

Aftercare
Immediately after surgery, the patient will be
moved to a recovery room until the affects of anesthesia have worn off. The patient will then be transferred
to the intensive care unit for further recovery. In the
GALE ENCYCLOPEDIA OF MEDICINE

Implantable cardioverter-defibrillator—A device
placed in the body to deliver an electrical shock to
the heart in response to a serious abnormal rhythm.
Wolff-Parkinson-White syndrome—An abnormal,
rapid heart rhythm, due to an extra pathway for the
electrical impulses to travel from the atria to the
ventricles.

intensive care unit, the heart will be monitored for any
disturbances in rhythm and the patient will be watched
for any signs of post-operative problems.

Risks
The risks of myocardial resection are based in
large part on the person’s underlying heart condition
and, therefore, vary greatly. The procedure involves
opening the heart, so the person is at risk for the
complications associated with major heart surgery
such as stroke, shock, infection, and hemorrhage.

Normal results
Anywhere from 5-25% of post-heart attack
patients do not survive open-heart surgery. The survivors have a 90% arrhythmia-free one-year survival
rate, (arrthymia is an irregular heart beat).

serious condition that affects both males and females
of any age.

Description
Most cases of myocarditis in the United States
originate from a virus, and the disease may remain
undiagnosed by doctors due to its general lack of
initial symptoms. The disease may also present itself
as an acute, catastrophic illness that requires immediate treatment. Although the inflammation or degeneration of the heart muscle that myocarditis causes
may be fatal, this disease often goes undetected. It
may also disguise itself as ischemic, valvular, or hypertensive heart disease.
An inflammation of the heart muscle may occur as
an isolated disorder or be the dominating feature of a
systemic disease (one that affects the whole body, like
systemic lupus erythematosus).

Causes and symptoms
While there are several contributing factors that
may lead to myocarditis, the primary cause is viral.
Myocarditis usually results from the Coxsackie B
virus, and may also result from measles, influenza,
chicken pox, hepatitis virus, or the adenovirus in children. If an acute onset of severe myocarditis occurs, a
patient may display the following symptoms:


Rhythm disturbances of the heart



Rapid heartbeat (Ventricular tachycardia)

Resources



Left or right ventricular enlargement

ORGANIZATIONS



Shortness of breath (Dyspnea)

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.



Pulmonary edema (the accumulation of fluid in the
lungs due to left-sided heart failure)



Swollen legs.

Dorothy Elinor Stonely

Myocarditis
Definition
Myocarditis is an inflammatory disease of the
heart muscle (myocardium) that can result from a
variety of causes. While most cases are produced by
a viral infection, an inflammation of the heart muscle
may also be instigated by toxins, drugs, and hypersensitive immune reactions. Myocarditis is a rare but
GALE ENCYCLOPEDIA OF MEDICINE

Additional causes of myocarditis include:


Bacterial infections, such as tetanus, gonorrhea, or
tuberculosis



Parasite infections, such as Chagas’ disease (which is
caused by an insect-borne protozoan most commonly seen in Central and South America)



Rheumatic fever



Surgery on the heart



Radiation therapy for cancer that is localized in the
chest, such as breast or lung cancer



Certain medications.

As of 1996, research has shown that illegal drugs
and toxic substances may also produce acute or
2547

Myocarditis

KEY TERMS

Myocarditis

determine the presence of myocarditis, or to rule out
other possible heart diseases that may lead to heart
failure.
Another measure used to diagnosis myocarditis is
the endomyocardial biopsy procedure. This invasive
catheterization procedure examines a biopsied, or
‘‘snipped,’’ piece of the endocardium (the lining membrane of the inner surface of the heart). The tissue
sample is examined to verify the presence of the disease, as well as to try to determine the infective cause.
An approach used only with a patient’s consent, this
procedure may also confirm acute myocarditis, allowing close monitoring of potential congestive heart
failure.
This illustration depicts the inflammation of the myocarditis,
the middle muscular layer of the heart wall. (Custom Medical
Stock Photo. Reproduced by permission.)

chronic injury to the myocardium. These studies also
indicate an increase in the incidence of toxic results
from the use of cocaine. This illegal drug causes coronary artery spasm, myocardial infarction (heart
attack), and arrhythmias, as well as myocarditis.
Further studies conducted in 1996 indicate that
malnutrition encourages the Coxsackie B virus to
flourish, leading to the potential development of myocarditis. Human immunodeficiency virus (HIV) is also
now recognized as a cause of myocarditis, though its
prevalence is not known.
Symptoms of myocarditis may start as fatigue,
shortness of breath, fever and aching of the joints, all
characteristic of a flu-like illness. In contrast to this
type of mild appearance, myocarditis may also appear
suddenly in the form of heart failure, or sudden cardiac
death without any prior symptoms. If an inflammation
of the heart muscle leads to congestive heart failure,
symptoms such as swollen feet and ankles, distended
neck veins, a rapid heartbeat, and difficulty breathing
while reclining may all appear.

Diagnosis
The best way to diagnose myocarditis may be
through a person’s observation of his or her own
symptoms, followed by a thorough medical history
and physical exam conducted by a doctor. Further
tests usually include laboratory blood studies and
echocardiography. An electrocardiogram (ECG) is
also routinely used due to its ability to detect a mild
case of the disease. Cardiac catheterization and angiography are additional diagnostic tests used to
2548

Treatment
While myocarditis is a serious condition, there is
no medical treatment necessary if it results from a
general viral infection. The only steps to recovery
include rest and avoidance of physical exertion.
Adequate rest becomes more important to recovery if
the case is severe myocarditis with signs of dilated
cardiomyopathy (disease of the heart muscles). In this
case, medical treatment for congestive heart failure
may include the following medications: angiotensin
converting enzyme (ACE) inhibitors, diuretics to
reduce fluid retention, digitalis to stimulate a stronger
heartbeat, and low-dose beta-blockers.
If myocarditis is caused by a bacterial infection,
the disease is treated with antibiotics to fight the infection. If severe rhythm disturbances are involved, cardiac assist devices, an ‘‘artificial heart,’’ or heart
transplantation may be the only option for complete
recovery.

Prognosis
The outlook for a diagnosed case of myocarditis
caused by a viral infection is excellent, with many cases
healing themselves spontaneously. Severe or acute
myocarditis may be controlled with medication to
prevent heart failure. Because this disease may be
mild or may be extreme and cause serious arrhythmias, the prognosis varies. Cases of myocarditis may
vary from complete healing (with or without significant scarring), to severe congestive heart failure leading to death or requiring a heart transplant.
Inflammation of the myocardium may also cause
acute pericarditis (inflammation of the outer lining of
the heart). Due to the potential effects of the disease,
including sudden death, it is imperative that proper
medical attention is obtained.
GALE ENCYCLOPEDIA OF MEDICINE

Adenovirus—One type of virus that can cause
upper respiratory tract infections.
Angiography—A procedure which uses x ray after
injecting a radiopaque substance to examine the
blood vessels and lymphatics.
Arrhythmia—An irregular heartbeat or action.
Cardiac catheterization—A diagnostic procedure
that gives a comprehensive examination of how the
heart and its blood vessels function; performed by
inserting one or more catheters through a peripheral blood vessel in the arm or leg.
Coxsackie B virus—A mild virus belonging to a
group of viruses (coxsackievirus) that may produce
a variety of illnesses, including myocarditis.
Echocardiography—A noninvasive diagnostic procedure that uses ultrasound to examine internal
cardiac structures.
Electrocardiogram—A record of the electrical
activity of the heart, with each wave being labeled
as P, Q, R, S, and T waves. Often used in the
diagnosis of cases of abnormal cardiac rhythm
and myocardial damage.
Hypertensive heart disease—High blood pressure
resulting in a disease of the heart.
Ischemic heart disease—Insufficient blood supply
to the heart muscle (myocardium).
Valvular heart disease—A disease of any one of the
four valves that controls blood flow into, through,
and out of the heart.
Ventricular tachycardia— An abnormally rapid
heartbeat. It includes a series of at least three
beats arising from a ventricular area at a rate of
more than 100 beats per minute, usually ranging
from 150-200 beats per minute.

Prevention
Although myocarditis is an unpredictable disease,
the following measures may help prevent its onset.
Individuals should:


Take extra measures to avoid infections, and obtain
appropriate treatment for infections.



Limit alcohol consumption to no more than one or
two drinks a day, if any.



Maintain current immunizations against diphtheria,
tetanus, measles, rubella, and polio.

GALE ENCYCLOPEDIA OF MEDICINE

Avoid anything that may cause the abnormal heart
to work too hard, including salt and vigorous
exercise.

Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Beth A. Kapes

Myoglobin test
Definition
Myoglobin is a protein found in muscle.
Myoglobin tests are done to evaluate a person who
has symptoms of a heart attack (myocardial infarction) or other muscle damage.

Purpose
Myoglobin holds oxygen inside heart and skeletal
muscle (muscles that attach to and move bones). It is
continually released into the blood in small amounts
due to normal turnover of muscle cells. Kidneys discard the myoglobin into urine.
When muscle is damaged, as in a heart attack,
larger amounts of myoglobin are released and blood
levels rise rapidly. Myoglobin is one of the first tests
done to determine if a person with chest pain is having
a heart attack, as it may be one of the first blood tests
to become abnormal.
Damage or injury to skeletal muscle also causes
myoglobin to be released into the blood.

Description
Heart attack must be diagnosed quickly.
Medications to prevent heart damage are effective
only within a limited number of hours. Yet, because
of their risk for excessive bleeding, these medications
are given only after a diagnosis of heart attack is made.
Myoglobin is one of several cardiac markers used
to make the diagnosis. Cardiac markers are substances
in blood whose levels rise in the hours following a
2549

Myoglobin test



KEY TERMS

Myomectomy

heart attack. Increased levels help diagnose a heart
attack; persistent normal levels rule it out.
Each cardiac marker rises, peaks, and returns to a
normal level according to its own timeline, or diagnostic window. Myoglobin is useful because it has the
earliest diagnostic window. It is the first marker to rise
after chest pain begins. Myoglobin levels rise within
two to three hours, and sometimes as early as 30
minutes. They peak after six to nine hours. The levels
return to normal within 24-36 hours.
Although a rise in myoglobin supports a diagnosis
of heart attack, it is not conclusive. Simultaneous
skeletal muscle damage could also cause the increase.
Myoglobin rules out, rather than proves, a diagnosis
in the following way. If myoglobin levels have not
risen after more than five hours, a heart attack in
unlikely. Normal levels in the first two to three hours
do not rule out an infarction.
The myoglobin test is sometimes repeated every
one to two hours to watch for the rise and peak.
Results are available within 30 minutes.
Myoglobin in large amounts is toxic to the kidney.
When a person has high amounts of myoglobin in the
blood, kidney function must be monitored.

KEY TERMS
Cardiac marker—A substance in the blood that
rises following a heart attack.
Diagnostic window—A cardiac marker’s timeline
for rising, peaking, and returning to normal after a
heart attack.
Myoglobin—A protein that holds oxygen in heart
and skeletal muscle. It rises after damage to either
of these muscle types.

Increased levels are also found with skeletal muscle damage or disease, such as an injury, muscular
dystrophy, or polymyositis. Myoglobin levels also rise
during renal failure because kidneys lose their ability
to clear myoglobin from blood.
Resources
BOOKS

Wu, Alan, editor. Cardiac Markers. Washington, DC:
American Association of Clinical Chemistry (AACC)
Press, 1998.

Nancy J. Nordenson

Preparation
This test requires 5 ml of blood. Collection of the
sample takes only a few minutes. A urine myoglobin
test requires 1 ml of urine collected into a urine collection cup.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve
discomfort.

Normal results
Normal results vary based on the laboratory and
method used.

Myomas see Uterine fibroids

Myomectomy
Definition
Myomectomy is the removal of fibroids (noncancerous tumors) from the wall of the uterus.
Myomectomy is the preferred treatment for symptomatic fibroids in women who want to keep their
uterus. Larger fibroids must be removed with an
abdominal incision, but small fibroids can be taken
out using laparoscopy or hysteroscopy.

Purpose
Abnormal results
Myoglobin levels and levels of other cardiac markers are usually considered before finally confirming a
diagnosis of heart attack. A level that has doubled
after one to two hours, even if the level is still in the
normal range, indicates a significant rise that may be
due to heart attack.
2550

A myomectomy can remove uterine fibroids that
are causing symptoms. It is an alternative to surgical
removal of the whole uterus (hysterectomy). The procedure can relieve fibroid-induced menstrual symptoms that have not responded to medication.
Myomectomy also may be an effective treatment for
infertility caused by the presence of fibroids.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

There is a risk that removal of the fibroids may
lead to such severe bleeding that the uterus itself will
have to be removed. Because of the risk of blood loss
during a myomectomy, patients may want to consider
banking their own blood before surgery.

Epidural anesthesia—A method of pain relief for
surgery in which local anesthetic is injected into
the epidural space in the middle and lower back.

Description
Usually, fibroids are buried in the outer wall of the
uterus and abdominal surgery is required. If they are
on the inner wall of the uterus, uterine fibroids can be
removed using hysteroscopy. If they are on a stalk
(pedunculated) on the outer surface of the uterus,
laparoscopy can be performed.
Removing fibroids through abdominal surgery is
a more difficult and slightly more risky operation than
a hysterectomy. This is because the uterus bleeds from
the sites where the fibroids were, and it may be difficult
or impossible to stop the bleeding. This surgery is
usually performed under general anesthesia, although
some patients may be given a spinal or epidural
anesthesia.
The incision may be horizontal (the ‘‘bikini’’ incision) or a vertical incision from the navel downward.
After separating the muscle layers underneath the
skin, the surgeon makes an opening in the abdominal
wall. Next, the surgeon makes an incision over each
fibroid, grasping and pulling out each growth.
Every opening in the uterine wall is then stitched
with sutures. The uterus must be meticulously repaired
in order to eliminate potential sites of bleeding or
infection. Then, the surgeon sutures the abdominal
wall and muscle layers above it with absorbable
stitches, and closes the skin with clips or nonabsorbable stitches.
When appropriate, a laparoscopic myomectomy
may be performed. In this procedure, the surgeon
removes fibroids with the help of a viewing tube
(laparoscope) inserted into the pelvic cavity through
an incision in the navel. The fibroids are removed
through a tiny incision under the navel that is much
smaller than the 4 or 5 inch opening required for a
standard myomectomy.
If the fibroids are small and located on the inner
surface of the uterus, they can be removed with a thin
telescope-like device called a hysteroscope. The hysteroscope is inserted into the vagina through the
cervix and into the uterus. This procedure does not
require any abdominal incision, so hospitalization is
shorter.
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
Surgeons often recommend hormone treatment
with a drug called leuprolide (Lupron) two to six
months before surgery in order to shrink the fibroids.
This makes the fibroids easier to remove. In addition,
Lupron stops menstruation, so women who are anemic have an opportunity to build up their blood count.
While the drug treatment may reduce the risk of excess
blood loss during surgery, there is a small risk that
temporarily-smaller fibroids might be missed during
myomectomy, only to enlarge later after the surgery is
completed.

Aftercare
Patients may need four to six weeks of recovery
following a standard myomectomy before they can
return to normal activities. Women who have had
laparoscopic or hysteroscopic myomectomies, however, can leave the hospital the day after surgery and
usually recovery completely within two to three days
to one to three weeks.

Risks
The risks of a myomectomy performed by a skilled
surgeon are about the same as hysterectomy (one of the
most common and safest surgeries). Removing multiple
fibroids is more difficult and slightly more risky.
Possible complications include:


Infection.



Blood loss.



The wall of the uterus may be weakened if the
removal of a large fibroid leaves a wound that
extends the complete thickness of the wall. Special
precautions may be needed in future pregnancies.
For example, the delivery may need to be performed
surgically (Caesarean section).



Adverse reactions to anesthesia.



Internal scarring (and possible infertility).

Since fibroids tend to appear and grow as a
woman ages (until menopause), it is possible that new
fibroids will appear after myomectomy.
2551

Myomectomy

Precautions

Myopathies

Resources



Nemaline myopathy

OTHER



Paramyotonia congenita



Periodic paralysis (hypokalemic and hyperkalemic
forms)



Mitochondrial myopathies.

Toaff, Michael E. ‘‘Myomectomy.’’ Alternatives to
Hysterectomy Page. <http://www.netreach.net/
~hysterectomyedu/myomecto.htm>.

Carol A. Turkington

Myopathies
Definition
Myopathies are diseases of skeletal muscle which
are not caused by nerve disorders. These diseases cause
the skeletal or voluntary muscles to become weak or
wasted.

Description
There are many different types of myopathies,
some of which are inherited, some inflammatory, and
some caused by endocrine problems. Myopathies are
rare and not usually fatal. Typically, effects are mild,
largely causing muscle weakness and movement
problems, and many are transitory. Only rarely will
patients become dependent on a wheelchair. However,
muscular dystrophy (which is technically a form of
myopathy) is far more severe. Some types of this disease are fatal in early adulthood.

Causes and symptoms
Myopathies are usually degenerative, but they are
sometimes caused by drug side effects, chemical poisoning, or a chronic disorder of the immune system.

Most of these genetic myopathies are dominant,
which means that a child needs to inherit only one
copy of the defective gene from one parent in order
to have the disease. The parent with the defective gene
also has the disorder, and each of this parent’s children
has a 50% chance of also inheriting the disease. Male
and female children are equally at risk.
However, one form of myotonia congenita and
some forms of nemaline myopathy must be inherited
from both parents, each of whom carry a recessive
defective gene but who do not have symptoms of the
disease. Each child of such parents has a 25% chance
of inheriting both genes and showing signs of the
disease, and a 50% chance of inheriting one defective
gene from only one parent. If the child inherited just
one defective gene, he or she would be a carrier but
would not show signs of the disease.
A few forms of centronuclear myopathy develop
primarily in males. Females who inherit the defective
gene are usually carriers without symptoms, like their
mothers, but they can pass on the disease to their sons.
Mitochondrial myopathies are inherited through the
mother, since sperm do not contain mitochondria.
(Mitochondria play a key role in energy production
in the body’s cells.)
The major symptoms associated with the genetic
myopathies include:


Central core disease: mild weakness of voluntary
muscles, especially in the hips and legs; hip displacement; delays in reaching developmental motor milestones; problems with running, jumping, and
climbing stairs develop in childhood



Centronuclear myopathy: weakness of voluntary
muscles including those on the face, arms, legs, and
trunk; drooping upper eyelids; facial weakness; foot
drop; affected muscles almost always lack reflexes



Myotonia congenita: voluntary muscles of the arms,
legs, and face are stiff or slow to relax after contracting (myotonia); stiffness triggered by fatigue, stress,
cold, or long rest periods, such as a night’s sleep;
stiffness can be relieved by repeated movement of
the affected muscles



Nemaline myopathy: moderate weakness of voluntary
muscles in the arms, legs, and trunk; mild weakness of
facial muscles; delays in reaching developmental

Genetic myopathies
Among their many functions, genes are responsible for overseeing the production of proteins important in maintaining healthy cells. Muscle cells produce
thousands of proteins. With each of the inherited
myopathies, a genetic defect is linked to a lack of, or
problem with, one of the proteins needed for normal
muscle cell function.
There are several different kinds of myopathy
caused by defective genes:


Central core disease



Centronuclear (myotubular) myopathy



Myotonia congenita

2552

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Paramyotonia congenita: stiffness (myotonia) of
voluntary muscles in the face, hands, and forearms;
attacks spontaneous or triggered by cold temperatures; stiffness made worse by repeated movement;
episodes of stiffness last longer than those seen in
myotonia congenita



Periodic paralysis: attacks of temporary muscle
weakness (muscles work normally between attacks);
in the hypokalemic (low calcium) form, attacks triggered by vigorous exercise, heavy meals (high in
carbohydrates), insulin, stress, alcohol, infection,
pregnancy; in the hyperkalemic (normal/high calcium) form, attacks triggered by vigorous exercise,
stress, pregnancy, missing a meal, steroid drugs, high
potassium intake



Mitochondrial myopathies: symptoms vary quite
widely with the form of the disease and may include
progressive weakness of the eye muscles (ocular myopathy), weakness of the arms and legs, or multisystem
problems primarily involving the brain and muscles.
Endocrine-related myopathies

In some cases, myopathies can be caused by a
malfunctioning gland (or glands), which produces
either too much or too little of the chemical messengers called hormones. Hormones are carried by the
blood and one of their many functions is to regulate
muscle activity. Problems in producing hormones can
lead to muscle weakness.
Hyperthyroid myopathy and hypothyroid myopathy affect different muscles in different ways.
Hyperthyroid myopathy occurs when the thyroid
gland produces too much thyroxine, leading to muscle
weakness, some muscle wasting in hips and shoulders,
and, sometimes, problems with eye muscles. The
hypothyroid type occurs when too little hormone is
produced, leading to stiffness, cramps, and weakness
of arm and leg muscles.

muscles. In fact, muscle tissue loss may be so severe
that the person may be unable to walk. Skin inflammation is also present. The cause is unknown, but viral
infection and antibiotics are associated with the condition. In some cases, dermatomyositis is associated
with rheumatologic disease or cancer. Polymyositis
involves inflammation of many muscles usually
accompanied by deformity, swelling, sleeplessness,
pain, sweating, and tension. It, too, may be associated
with cancer. Myositis ossificans is a rare inherited
disease in which muscle tissue is replaced by bone,
beginning in childhood.
Muscular dystrophy
While considered to be a separate group of diseases, the muscular dystrophies also technically
involve muscle wasting and can be described as myopathies. These relatively rare diseases appear during
childhood and adolescence, and are caused by muscle
destruction or degeneration. They are a group of
genetic disorders caused by problems in the production of key proteins.
The forms of muscular dystrophy (MD) differ
according to the way they are inherited, the age of
onset, the muscles they affect, and how fast they progress. The most common type is Duchenne MD,
affecting one or two in every 10,000 boys. Other
types of MD include Becker’s, myotonic dystrophy,
limb-girdle MD, and facioscapulohumeral MD.

Diagnosis
Early diagnosis of myopathy is important so that
the best possible care can be provided as soon as
possible. An experienced physician can diagnose a
myopathy by evaluating a person’s medical history
and by performing a thorough physical exam.
Diagnostic tests can help differentiate between the
different types of myopathy, as well as between myopathy and other neuromuscular disorders. If the doctor suspects a genetic myopathy, a thorough family
history will also be taken.
Diagnostic tests the doctor may order include:

Inflammatory myopathies
Some myopathies are inflammatory, leading to
inflamed, weakened muscles. Inflammation is a protective response of injured tissues characterized by
redness, increased heat, swelling, and/or pain in the
affected area. Examples of this type include polymyositis, dermatomyositis, and myositis ossificans.
Dermatomyositis is a disease of the connective
tissue that also involves weak, tender, inflamed
GALE ENCYCLOPEDIA OF MEDICINE



Measurements of potassium in the blood



Muscle biopsy



Electromyogram (EMG).

Treatment
Treatment depends on the specific type of myopathy the person has:
2553

Myopathies

motor milestones; decreased or absent reflexes in
affected muscles; long, narrow face; high-arched
palate; jaw projects beyond upper part of the face

Myopia

KEY TERMS
Electromyogram (EMG)—A diagnostic test that
records the electrical activity of muscles. In the
test, small electrodes are placed on or in the skin;
the patterns of electrical activity are projected on a
screen or over a loudspeaker. This procedure is
used to test for muscle disorders, including muscular dystrophy.
Inflammation—A protective response of injured
tissues characterized by redness, increased heat,
swelling, and/or pain in the affected area.
Voluntary muscles—Muscles producing voluntary
movement.



Periodic paralysis: medication and dietary changes



Hyperthyroid or hypothyroid myopathy: treatment
of the underlying thyroid abnormality



Myositis ossificans: medication may prevent abnormal bone formation, but there is no cure following
onset



Central core disease: no treatment



Nemaline myopathy: no treatment



Centronuclear (myotubular) myopathy: no treatment



Paramyotonia congenita: treatment often unnecessary



Myotonia congenita: drug treatment (if necessary),
but drugs do not affect the underlying disease, and
attacks may still occur.

Prognosis
The prognosis for patients with myopathy
depends on the type and severity of the individual
disease. In most cases, the myopathy can be successfully treated and the patient returned to normal life.
Muscular dystrophy, however, is generally a
much more serious condition. Duchenne’s MD is
usually fatal by the late teens; Becker’s MD is less
serious and may not be fatal until the 50s.
Resources
ORGANIZATIONS

Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson, AZ 85718. (800) 572-1717. <http://
www.mdausa.org>.

Carol A. Turkington
2554

Myopia
Definition
Myopia is the medical term for nearsightedness.
People with myopia see objects more clearly when they
are close to the eye, while distant objects appear
blurred or fuzzy. Reading and close-up work may be
clear, but distance vision is blurry.

Description
To understand myopia it is necessary to have a
basic knowledge of the main parts of the eye’s focusing
system: the cornea, the lens, and the retina. The cornea
is a tough, transparent, dome-shaped tissue that covers the front of the eye (not to be confused with the
white, opaque sclera). The cornea lies in front of the
iris (the colored part of the eye). The lens is a transparent, double-convex structure located behind the
iris. The retina is a thin membrane that lines the rear
of the eyeball. Light-sensitive retinal cells convert
incoming light rays into electrical signals that are
sent along the optic nerve to the brain, which then
interprets the images.
In people with normal vision, parallel light rays
enter the eye and are bent by the cornea and lens (a
process called refraction) to focus precisely on the
retina, providing a crisp, clear image. In the myopic
eye, the focusing power of the cornea (the major
refracting structure of the eye) and the lens is too
great with respect to the length of the eyeball. Light
rays are bent too much, and they converge in front of
the retina. This inaccuracy is called a refractive error.
In other words, an overfocused fuzzy image is sent to
the brain.
There are many types of myopia. Some common
types include:



Physiologic



Pathologic



Acquired.

By far the most common form, physiologic myopia develops in children sometime between the ages of
5-10 years and gradually progresses until the eye is
fully grown. Physiologic myopia may include refractive myopia (the cornea and lens-bending properties
are too strong) and axial myopia (the eyeball is too
long). Pathologic myopia is a far less common
abnormality. This condition begins as physiologic
myopia, but rather than stabilizing, the eye continues
GALE ENCYCLOPEDIA OF MEDICINE

Genetic profile
Eyecare professionals have debated the role of
genetics in the development of myopia for many
years. Some believe that a tendency toward myopia
may be inherited, but the actual disorder results from a
combination of environmental and genetic factors.
Environmental factors include close work; work with
computer monitors or other instruments that emit
some light (electron microscopes, photographic equipment, lasers, etc.); emotional stress; and eye strain.
A variety of genetic patterns for inheriting myopia
have been suggested. One explanation for lack of
agreement is that the genetic profile of high myopia
(defined as a refractive error greater than -6 diopters)
may differ from that of low myopia. Some researchers
think that high myopia is determined by genetic factors to a greater extent than low myopia.
Another explanation for disagreement regarding
the role of heredity in myopia is the sensitivity of the
human eye to very small changes in its anatomical
structure. Since even small deviations from normal
structure cause significant refractive errors, it may be
difficult to single out any specific genetic or environmental factor as their cause.
Since 1992, genetic markers that may be associated with genes for myopia have been located on
human chromosomes 1, 2, 12, and 18. There is some
genetic information on the short arm of chromosome
2 in highly myopic people. Genetic information for
low myopia appears to be located on the short arm
of chromosome 1, but it is not known whether this
information governs the structure of the eye itself or
vulnerability to environmental factors.
In 1998 a team of American researchers presented
evidence that a gene for familial high myopia with an
autosomal dominant transmission pattern could be
mapped to human chromosome 18 in eight North
American families. The same group also found a second locus for this form of myopia on human chromosome 12 in a large German/Italian family. In 1999 a
group of French researchers found no linkage between
chromosome 18 and 32 French families with familial
high myopia. These findings have been taken to
GALE ENCYCLOPEDIA OF MEDICINE

indicate that more than one gene is involved in the
transmission of the disorder.
It has been known for some years that a family
history of myopia is one of the most important risk
factors for developing the condition. Only 6%-15%
of children with myopia come from families in which
neither parent is myopic. In families with one
myopic parent, 23%-40% of the children develop
myopia. If both parents are myopic, the rate rises
to 33%-60% for their children. One American study
found that children with two myopic parents are
6.42 times as likely to develop myopia themselves
as children with only one or no myopic parents. The
precise interplay of genetic and environmental factors in these family patterns, however, is not yet
known.
One multigenerational study of Chinese subjects
indicated that subjects in the third generation had a
higher risk of developing myopia even if their parents
were not myopic. The researchers concluded that, at
least in China, the genetic factors in myopia have
remained constant over the past three generations
while the environmental factors have intensified. The
increase in the percentage of people with myopia over
the last 50 years in the United States has led American
researchers to the same conclusion.
The debate continued with more recent reports. In
the summer of 2004, one report said that scientists
were close to identifying the myopia gene, located on
chromosome 11. Another report reviewed several
studies and claimed that lifestyle was to blame for
myopia. For instance, a study found that 80% of 14to 18-year old boys studying in schools in Israel that
emphasize reading religious texts have myopia, while
the rates for boys in state school was just 30%. It is
likely that genes and environment play a role.
Myopia is the most common eye disorder in
humans around the world. It affects between 25%
and 35% of the adult population in the United States
and the developed countries, but is thought to affect as
much as 40% of the population in some parts of Asia.
Some researchers have found slightly higher rates of
myopia in women than in men.
The age distribution of myopia in the United
States varies considerably. Five-year-olds have the
lowest rate of myopia (less than 5%) of any age
group. The prevalence of myopia rises among children
and adolescents in school until it reaches the 25%35% mark in the young adult population. It declines
slightly in the over-45 age group; about 20% of 65year-olds have myopia. The figure drops to 14% for
Americans over 70.
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Myopia

to enlarge at an abnormal rate (progressive myopia).
This more advanced type of myopia may lead to
degenerative changes in the eye (degenerative myopia). Acquired myopia occurs after infancy. This condition may be seen in association with uncontrolled
diabetes and certain types of cataracts. Antihypertensive drugs and other medications can also affect the
refractive power of the lens.

Myopia

Retina
Cornea

decreases and myopia does not become evident until
later. This change is one reason why some researchers
think that myopia is an acquired rather than an inherited trait.
The symptoms of myopia are blurred distance
vision, eye discomfort, squinting, and eye strain.

Light

Diagnosis
Lens

Normal eye

Light

Nearsightedness (myopia)

Myopia, or nearsightedness, is a condition of the eye in which
objects are seen more clearly when close to the eye while
distant objects appear blurred or fuzzy. (Illustration by
Electronic Illustrators Group.)

Other factors that affect the demographic distribution of myopia are income level and education. The
prevalence of myopia is higher among people with
above-average incomes and educational attainments.
Myopia is also more prevalent among people whose
work requires a great deal of close focusing, including
work with computers.

Causes and symptoms
Myopia is said to be caused by an elongation of
the eyeball. This means that the oblong (as opposed to
normal spherical) shape of the myopic eye causes the
cornea and lens to focus at a point in front of the
retina. A more precise explanation is that there is an
inadequate correlation between the focusing power of
the cornea and lens and the length of the eye.
People are generally born with a small amount of
hyperopia (farsightedness), but as the eye grows this
2556

The diagnosis of myopia is typically made during
the first several years of elementary school when a
teacher notices a child having difficulty seeing the
chalkboard, reading, or concentrating. The teacher
or school nurse often recommends an eye examination
by an ophthalmologist or optometrist. An ophthalmologist—M.D. or D.O. (Doctor of Osteopathy)—is
a medical doctor trained in the diagnosis and treatment of eye problems. Ophthalmologists also perform
eye surgery. An optometrist (O.D.) diagnoses and
manages and/or treats eye and visual disorders. In
many states, optometrists are licensed to use diagnostic and therapeutic drugs.
A patient’s distance vision is tested by reading
letters or numbers on a chart posted a set distance
away (usually 20 ft). The doctor asks the patient to
view images through a variety of lenses to obtain the
best correction. The doctor also examines the inside of
the eye and the retina. An instrument called a slit lamp
is used to examine the cornea and lens. The eyeglass
prescription is written in terms of diopters (D), which
measure the degree of refractive error. Mild to moderate myopia usually falls between -1.00D and -6.00D.
Normal vision is commonly referred to as 20/20 to
describe the eye’s focusing ability at a distance of 20
ft from an object. For example, 20/50 means that a
myopic person must stand 20 ft away from an eye
chart to see what a normal person can see at 50 ft.
The larger the bottom number, the greater the myopia.

Treatment
People with myopia have three main options for
treatment: eyeglasses, contact lenses, and for those
who meet certain criteria, refractive eye surgery.
Eyeglasses
Eyeglasses are the most common method used to
correct myopia. Concave glass or plastic lenses are
placed in frames in front of the eyes. The lenses are
ground to the thickness and curvature specified in the
eyeglass prescription. The lenses cause the light rays to
diverge so that they focus further back, directly on the
retina, producing clear distance vision.
GALE ENCYCLOPEDIA OF MEDICINE

Contact lenses are a second option for treatment.
Contact lenses are extremely thin round discs of plastic
that are worn on the eye in front of the cornea.
Although there may be some initial discomfort, most
people quickly grow accustomed to contact lenses.
Hard contact lenses, made from a material called
PMMA, are virtually obsolete. Rigid gas permeable
lenses (RGP) are made of plastic that holds its shape
but allows the passage of some oxygen into the eye.
Some believe that RGP lenses may halt or slow the
progression of myopia because they maintain a constant, gentle pressure that flattens the cornea. As of
2001, the National Eye Institute is conducting an
ongoing study of RGP lenses called the Contact Lens
and Myopia Progression (CLAMP) Study, with
results to be published in 2003.
A procedure called orthokeratology acts on this
principle of ‘‘corneal molding.’’ However, when contact lenses are discontinued for a period of time, the
cornea will generally go back to its original shape.
Rigid gas permeable lenses offer crisp, clear, sight.
Soft contact lenses are made of flexible plastic and
can be up to 80% water. Soft lenses offer increased
comfort and the advantage of extended wear; some
can be worn continuously for up to one week. While
oxygen passes freely through soft lenses, bacterial contamination and other problems can occur, requiring
replacement of lenses on a regular basis. It is very
important to follow the cleaning and disinfecting regimens prescribed because protein and lipid buildup can
occur on the lenses, causing discomfort or increasing
the risk of infection. Contact lenses offer several benefits over glasses, including: better vision, less distortion, clear peripheral vision, and cosmetic appeal. In
addition, contacts do not steam up from perspiration
or changes in temperature.

FDA, though certain lasers are in various stages of
approval at a given time. Patients should check with
the FDA and ask for patient references when choosing
a LASIK provider.
RADIAL KERATOTOMY. Radial keratotomy (RK),
the first of these procedures made available, has a
high associated risk. It was first developed in Japan
and the Soviet Union, and introduced into the United
States in 1978. The surgeon uses a delicate diamondtipped blade, a microscope, and microscopic instruments to make several spoke-like ‘‘radial’’ incisions in
the non-viewing (peripheral) portion of the cornea. As
the incisions heal, the slits alter the curve of the cornea,
making it more flat, which may improve the focus of
images onto the retina.
PHOTOREFRACTIVE KERATECTOMY. Photorefractive
keratectomy (PRK) involves the use of a computer to
measure the shape of the cornea. Using these measurements, the surgeon applies a computer-controlled
laser to make modifications to the cornea. The PRK
procedure flattens the cornea by vaporizing small
amounts of tissue from the cornea’s surface. It is
important to make sure the laser being used is FDA
approved. Photorefractive keratectomy can be used to
treat mild to moderate forms of myopia. The cost is
approximately $2,000 per eye.
LASER-ASSISTED IN-SITU KERATOMILEUSIS. Laserassisted in-situ keratomileusis (LASIK) is the newest
of these procedures. It is recommended for moderate
to severe cases of myopia. A variation on the PRK
method, LASIK uses lasers and a cutting tool called a
microkeratome to cut a circular flap on the cornea.
The flap is flipped back to expose the inner layers of
the cornea. The cornea is treated with a laser to change
the shape and focusing properties, then the flap is
replaced.

Risks
Refractive eye surgery
For people who find glasses and contact lenses
inconvenient or uncomfortable, and who meet selection criteria regarding age, degree of myopia, general
health, etc., refractive eye surgery is a third treatment
alternative. There are three types of corrective surgeries available as of 2001: 1) radial keratotomy
(RK), 2) photorefractive keratectomy (PRK), and 3)
laser-assisted in-situ keratomileusis (LASIK).
Refractive eye surgery improves myopic vision by permanently changing the shape of the cornea so that
light rays focus properly on the retina. These procedures are performed on an outpatient basis and generally take 10-30 minutes. LASIK is approved by the
GALE ENCYCLOPEDIA OF MEDICINE

All of these surgical procedures carry risks, the
most serious being corneal scarring, corneal rupture,
infection, cataracts, and loss of vision. In addition, a
study published in March 2001 warned that mountain
climbers who have had LASIK surgery should be
aware of possible changes in their vision at high altitudes. The lack of oxygen at high altitudes causes
temporary changes in the thickness of the cornea.
Since refractive eye surgery does not guarantee 20/
20 vision, it is important to have realistic expectations
before choosing this treatment. In a 10-year study
conducted by the National Eye Institute between
1983 and 1993, more than 50% of people with radial
keratotomy gained 20/20 vision, and 85% passed a
2557

Myopia

Contact lenses

Myopia

KEY TERMS
Accommodation—The ability of the lens to change
its focus from distant to near objects. It is achieved
through the action of the ciliary muscles that change
the shape of the lens.
Cornea—The transparent structure of the eye over
the lens that is continous with the sclera in forming
the outermost, protective, layer of the eye.
Diopter (D)—A unit of measure for describing refractive power.
Laser-assisted in-situ keratomileusis (LASIK)—A procedure that uses a cutting tool and a laser to modify the
cornea and correct moderate to high levels of myopia.
Lens—The transparent, elastic, curved structure
behind the iris (colored part of the eye) that helps
focus light on the retina.
Ophthalmologist—A physician specializing in the
medical and surgical treatment of eye disorders.
Optic nerve—A bundle of nerve fibers that carries
visual messages from the retina in the form of electrical signals to the brain.
Optometrist—A medical professional who examines
and tests the eyes for disease and treats visual disorders by prescribing corrective lenses and/or vision
therapy. In many states, optometrists are licensed to
use diagnostic and therapeutic drugs to treat certain
ocular diseases.
Orthokeratology—A method of reshaping the cornea using a contact lens. It is not considered a permanent method to reduce myopia.

driving test (requiring 20/40 vision) after surgery,
without glasses or contact lenses. Even if the patient
gains near-perfect vision, however, there are potentially irritating side effects, such as postoperative
pain, poor night vision, variation in visual acuity,
light sensitivity and glare, and optical distortion.
Refractive eye surgeries are considered elective procedures and are not always covered by insurance plans.
Myopia treatments under research include corneal implants and permanent surgically placed contact
lenses.

Alternative treatments
Some eye care professionals recommend treatments to help improve circulation, reduce eye strain,
and relax the eye muscles. It is possible that by
2558

Peripheral vision—The ability to see objects that are
not located directly in front of the eye. Peripheral
vision allows people to see objects located on the
side or edge of their field of vision.
Photorefractive keratectomy (PRK)—A procedure
that uses an excimer laser to make modifications to
the cornea and permanently correct myopia.
Radial keratotomy (RK)—A surgical procedure
involving the use of a diamond-tipped blade to
make several spoke-like slits in the peripheral (nonviewing) portion of the cornea to improve the focus
of the eye and correct myopia by flattening the
cornea.
Refraction—The bending of light rays as they pass
from one medium through another. Used to
describe the action of the cornea and lens on light
rays as they enter they eye. Also used to describe
the determination and measurement of the eye’s
focusing system by an optometrist or
ophthalmologist.
Refractive eye surgery—A general term for surgical
procedures that can improve or correct refractive
errors by permanently changing the shape of the
cornea.
Retina—The light-sensitive layer of tissue in the back
of the eye that receives and transmits visual signals to
the brain through the optic nerve.
Visual acuity—The ability to distinguish details and
shapes of objects.

combining exercises with changes in behavior, the
progression of myopia may be slowed or prevented.
Alternative treatments include: visual therapy (also
referred to as vision training or eye exercises); discontinuing close work; reducing eye strain (taking a rest
break during periods of prolonged near vision tasks);
and wearing bifocals to decrease the need to accommodate when doing close-up work.

Prognosis
Glasses and contact lenses can (but not always)
correct the patient’s vision to 20/20. Refractive surgery can make permanent improvements for the right
candidates.
While the genetic factors that influence the transmission and severity of myopia cannot be changed,
GALE ENCYCLOPEDIA OF MEDICINE

Eye strain can be prevented by using sufficient
light for reading and close work, and by wearing corrective lenses as prescribed. Everyone should have
regular eye examinations to see if their prescription
has changed or if any other problems have developed.
This is particularly important for people with high
(degenerative) myopia who are at a greater risk of
developing retinal detachment, retinal degeneration,
glaucoma, or other problems.
Resources

Myositis

some environmental factors can be modified. They
include reducing close work; reading and working in
good light; taking frequent breaks when working at a
computer or microscope for long periods of time;
maintaining good nutrition; and practicing visual therapy (when recommended).

Myositis
Definition
Myositis is a rare disease in which the muscle
fibers and skin are inflamed and damaged, resulting
in muscle weakness. There are several types of myositis
that affect different parts of the body.

Description
The persistent inflammation that is associated with
myositis develops slowly over weeks to months and
often years, with progressive weakening of the muscles.
Later in the course of the disease development muscle
wasting or shortening (contracture) may develop.
Myositis can range in severity from mild to debilitating.
The forms of myositis include:

PERIODICALS

‘‘Blame lifestyle for myopia, not genes.’’ Biotech Week July
28, 2004: 65.
Naiglin. L., et al. ‘‘Familial high myopia: evidence of an
autosomal dominant mode of inheritance and genetic
heterogeneity.’’ Annals of Genetics 42, no. 3 (1999):
140-146.
Pacell, R, et al. ‘‘Role of genetic factors in the etiology of
juvenile-onset myopia based on a longitudinal study of
refractive error.’’ Optometry and Visual Science 76
(June 1999): 381-386.
Saw, SM, et al. ‘‘Myopia: gene-environment interaction.’’
Annals of the Academy of Medicine of Singapore 29
(May 2000): 290-297.
‘‘Scientists close to identifying myopia gene.’’ Chemistry and
Industry August 16, 2004: 7.
Wu, MM, and MH Edwards. ‘‘The effect of having myopic
parents: an analysis of myopia in three generations.’’
Optometry and Visual Science 76 (June 1999): 341-342.



Polymyositis (PM) inflames and weakens muscles in
many parts of the body, and especially those parts
closest to the trunk. With polymyositis, dysphagia
(difficulty, discomfort or pain in speaking or swallowing), fatigue, and pain in the muscles are common. PM rarely affects people under the age of 20,
with the peak onset between the ages of 30 and 60.



Dermatomyositis (DM) affects both the muscle fibers
and skin by damaging the tiny blood vessels (capillaries) that supply blood to the muscle and skin,
resulting in muscle weakness, pain, and fatigue. In
addition the affected person develops a distinctive
patchy, reddish rash on the eyelids, cheeks, bridge
of the nose, back or upper chest, elbows, knees, and
knuckles. There may also be hardened, tender bumps
(possibly caused by inflammation of fat) under the
skin. DM can occur at any age and is more common
in females than males.



Inclusion Body Myositis (IBM) typically begins after
age 50, and is characterized by gradual weakening of
muscles throughout the body, including the wrists or
fingers, development of dysphagia, and atrophy of
forearms and/or thigh muscles. Unlike the other
types of myositis, IBM occurs more often in men
than women, and also does not respond very well to
drug therapy.



Juvenile myositis (JM) involves muscle weakness,
skin rash, and dysphagia in children. A common
characteristic of JM is the formation of calcium
deposits in the muscle (calcinosis). These deposits
are hard and sometimes painful lumps of calcium
under the skin that appear on the child’s fingers,
hands, elbows, and knees. Painful sores may appear
if the lumps break through the skin. The child may

ORGANIZATIONS

American Academy of Ophthalmology. PO Box 7424, San
Francisco, CA 94120-7424. (415) 561-8500.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100.
<http://www.aoanet.org>.
International Myopia Prevention Association. RD No. 5,
Box 171, Ligonier, PA 15658. (412) 238-2101.
Myopia International Research Foundation. 1265
Broadway, Room 608, New York, NY 10001. (212)
684-2777.
National Eye Institute. Bldg. 31 Rm 6A32, 31 Center Dr.,
MSC 2510, Bethesda, MD 20892-2510. (301) 496-5248.
2020@nei.nih.gov. <http://www.nei.nih.gov>.

Rebecca J. Frey, PhD
Risa Palley Flynn
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

2559

Myositis

also suffer from contractures, which is muscle shortening that results in joints staying bent. About half of
the children with JM will have pain in their muscles.
Myositis is rare, affecting about 10 in one million
people each year. DM and PM affect mostly women in
the forties and fifties but men and children can also
affect be affected, some at a young age (between the
ages of 5 and 15). About 40,000 people in the United
States may have this disease, with about 3,000 to 5,000
children affected.

Causes and symptoms
Myositis is thought to be an autoimmune disease.
The body normally fights infections and disease by
producing antibodies and white blood cells called lymphocytes in a process called the immune response. In
an autoimmune disease, the immune response is overactive, and the immune system attacks and destroys the
body’s own normal healthy tissues. There is no known
cause to the autoimmune response that results in myositis. However, investigators are studying whether the
disease is triggered by such environmental agents as the
organism that causes toxoplasmosis, Toxoplasma gondii, the Lyme disease organism, Borrelia burgdorferi,
the coxsackievirus, or by food allergies. Some cases of
IBM are thought to be inherited.
The first symptoms of most types of myositis are
weakness and pain in the muscles of the hips and
shoulders. The affected person may have trouble getting up from a chair, lifting the arms above the head, or
climbing stairs, and may be too tired to walk or stand.
DM and PM mostly affects muscles that are close to
and within the trunk of the body, while IBM involves a
wider range of muscles. Myositis may make it difficult
for the person to speak or swallow. When the disease
affects the lungs or chest muscles, the person may have
difficulty breathing. If the person has DM, they may
develop characteristic rashes. Other symptoms may
include fever and joint pain and swelling.
The first signs of JM is usually a red and patchy
skin rash and/or a red or purplish rash on the eyelids
or cheeks that look like allergies. Weak muscles may
develop at the same time as the rash, or may develop
days, weeks, or months after the appearance of the
rash. Other symptoms of JM include falling, a weaker
voice (dysophonia), or dysphagia. Calcinosis usually
develops later during the course of the disease.

Diagnosis
Myositis can a difficult disease to diagnose,
because it is rare, because the symptoms develop
2560

slowly, and because it can be mistaken for other diseases causing muscle weakness such as limb-girdle
muscular dystrophy. Many cases of myositis go
undiagnosed for years. The health care provider
must rule out other conditions such as hypothyroidism,
toxin exposure, drug reactions, and genetic disorders
that can also affect muscles. The physical examination
will include a complete medical history focusing on
symptoms and when they occurred, and blood tests for
autoantibodies and muscle enzymes (for example,
creatine kinase (CK), which when present in the
blood indicates muscle damage). Specialized tests
may also be performed, including:


an electromyogram, which measures the electrical
pattern of the muscles



a muscle biopsy, in which a small piece of muscle is
removed, stained, and examined by microscopic
techniques to determine if muscle fibers are damaged
and whether the muscle fibers are being infiltrated by
cells of the immune system



magnetic resonance imaging (MRI) to identify areas
of muscle inflammation.

Treatment
There is no cure for myositis. However, prompt
and aggressive treatment may reduce muscle inflammation and prevent muscle weakness from progressing. Because of the many different kinds of symptoms
and a wide range of reactions to different drugs, each
person’s treatment for myositis should be
individualized.
Drugs that are used for treatment include corticosteroids, such as prednisone, to reduce inflammation
and improve the body’s reaction to infections.
Corticosteroids are usually taken in the form of pills,
but may also be injected. The amount of creatine
kinase (CK) levels in the blood are monitored to
determine how well the medicine is working.
Corticosteroids may produce a number of side effects,
such as weight gain, difficulties in fighting infections,
psychiatric changes, sleeping troubles, water retention, bone thinning, facial swelling, diabetes, and cataracts. Corticosteroid therapy usually leads to
improvement in myositis symptoms within two
to three months, after which the dose can be lowered
to avoid the side effects. If the dose of corticosteriods
is going to be reduced, it is essential to lower the dose
over a period of time.
Immunosuppressant drugs are used to slow down
the immune system’s attack on healthy tissue and
improve skin rashes. Persons may be prescribed these
GALE ENCYCLOPEDIA OF MEDICINE

Intravenous immunoglobulin (IVIg) appears to
aid in improving muscle strength in many persons
with myositis, particularly those with DM. It may be
less effective in PM, and its role in treating IBM
requires more study, although it has been shown to
help some patients with IBM if they are diagnosed
early. Immunoglobulins are normal proteins in the
blood that attack anything foreign in the body, such
as viruses and bacteria. IVIg is made from donated
blood plasma from people with normal immune systems. Side effects from the the use of IVIg include
headache and flu-like symptoms.
Topical cream or ointment forms of some of the
medicines, such as prednisone and tacrolimus, can be
used to heal and soothe the rash associated with DM.
Non-steriodal anti-inflammatory drugs (NSAIDS)
such as aspirin or ibuprofen can be used for pain relief.
Calcinosis can be treated with prednisone, plaquenil
(also called hydroxychloroquine), intravenous immunoglobin (IVIG), cyclosporine, and methotrexate.
After drug treatment results in improvement, the
affected person begins a program of regular stretching
exercises to maintain range of motion in the weakened
arms and legs. Physical therapy may be used to prevent permanent muscle shortening. Whirlpool baths,
heat, and gentle massages may also provide relief.
Adequate rest is necessary, and affected persons
should take frequent breaks throughout the day and
limit their activity.
Patients with throat problems should be evaluated
by a speech therapist who can evaluate the swallowingrelated problems and make recommendations regarding diet changes and safe swallowing techniques.
Before a woman with myositis becomes pregnant,
she should discuss the medicines that she is taking with
her health care provider and evaluate the possible risks
that she and the baby face if she does become pregnant. Many of the drugs used in the treatment of
myositis may be harmful to the fetus or to a breastfed baby.
It is recommended that a doctor experienced in
the treatment of myositis, assisted by a rheumatologist, dermatologist, or neurologist, be consulted.
Oftentimes a patient may have to be treated at a
GALE ENCYCLOPEDIA OF MEDICINE

major medical center, where the disease has been
seen and treated before.

Alternative treatment
Various supplements may be used in conjunction
with traditional treatment to offset side effects of conventional drug treatment. The use of these suppplements should be approved by the primary health care
provider.
Immunosuppressant drugs such as methotroxate
and cyclophosphamide increase the risk of infection,
so a healthy well-balanced diet is required.
Methotroxate impairs the body’s ability to absorb
folic acid, so foods high in folic acid, such as leafy
green vegetables, fruits, and folate-fortified breads
and cereals are recommended. The use of folate supplements may also be recommended by the health care
provider. Vitamins C and E can be used to help with
the pain and infections associated with calcinosis.
Corticosteroids may have multiple side effects
when taken for long periods of time at high doses.
Calcium and Vitamin D are recommended to lower
the risk of osteoporosis, a common side effect of prednisone use. Hypertension and fluid retention may be
controlled by a diet low in salt. Steroid-induced diabetes (hyperglycemia) can be aided by a diet low in
sugar and other simple carbohydrates. Proteinuria, in
which the body breaks down protein faster than normal, may mean that more protein should be included
in the diet.
Weight gain associated with the use of corticosteroids can be managed by the use of the DASH (Dietary
Approach to Stop Hypertension) diet, which is high in
fruits, vegetables, dietary fiber, and low-fat dairy products. Information concerning this diet, developed by
the National Institutes of Health, can be found at
[www.nhlbi.nih.gov/health/public/heart/hbp/dash/].
Weight gain can overtax weakened muscles and
should be avoided if possible.

Prognosis
The progression of PM and DM varies from person to person, but the lifespan of an affected person is
not usually significantly affected. DM responds more
favorably to therapy than PM. Overall, many patients
do improve and have a functional recovery. About
half of the patients recover and can discontinue treatment within 5 years of beginning treatment. In children the chances of a cure are better than in adults,
although some children do suffer a relapse. Of the
remaining 50%, about 20% will still have the active
2561

Myositis

drugs to control myositis if they are unable to tolerate
corticosteroids or if the corticosteroids are not accomplishing the desired degree of treatment. Immunosuppressant drugs may also be used in conjunction with
corticosteroids so that lower doses of corticosteroids
can be used. Immunosuppressant drugs include
azathioprine, methotrexate, cyclosporine, tacrolimus,
etanercept, and mycophenolate mofetil.

Myotonic dystrophy

KEY TERMS
Coxsackievirus—Enterovirus causing a disease
resembling poliomyelitis but without paralysis
Dysphagia—Medical term for any difficulty, discomfort or pain when swallowing
Limb-girdle muscular dystrophy—An autosomal
recessive form of muscular dystrophy that appears
anywhere from late childhood to middle age and is
characterized by progressive muscular weakness
beginning either in the shoulder or pelvic girdle;
the disease usually progresses slowly with cardiopulmonary complications in the later stages

The Myositis Association (TMA). 1233 20th St. NW, Suite
402Washington, DC 20036. Telephone: (202) 887-0082;
Fax: (202) 466-8940; Web site: www.myositis.org/
OTHER

Progressive Management. 21st Century Complete Medical
Guide to Myositis, including Dermatomyositis and
Polymyositis, Authoritative Government Documents,
Clinical References, and Practical Information for
Patients and Physicians. (CD-ROM). Washington, DC:
Progressive Management, 2004.

Judith Sims

Myositis see Myopathies
Myotonia atrophica see Myotonic dystrophy

disease and will require ongoing treatment, while up to
30% may have some remaining muscle weakness.
However, IBM is disabling, and most patients will
require the use of an assistive device such as a cane,
walker, or wheel chair. The older the patient is when
contracting IBM, the more rapidly the disease
progresses.

Prevention
There is no known way to prevent myositis.
Resources
BOOKS

Kilpatrick, James R. (Compiler). Coping with a Myositis
Disease. Written by Myositis Patients Telling Their
Personal Story of Dealing with this Muscle Disease.
Athens, TX: Kilpatrick Publishing Company, 2000.
Icon Health Publications. Myositis: A Medical Dictionary,
Bibliography, and Annotated Research Guide to Internet
Resources. San Diego, CA: Icon Health Publications,
2004.
Icon Health Publications. The Official Patient’s Sourcebook
on Dermatomyositis: A Revised and Updated Directory
for the Internet Age. San Diego, CA: Icon Health
Publications, 2002.
Icon Health Publications. The Official Patient’s Sourcebook
on Inclusion Body Myositis: A Revised and Updated
Directory for the Internet Age. San Diego, CA: Icon
Health Publications, 2002.
ORGANIZATIONS

Muscular Dystrophy Association - USA, National
Headquarters. 3300 E. Sunrise Drive, Tucson, AZ
85718. Telephone: (800) 572-1717. Web site:
www.mdausa.org/
Myositis Support Group. 205 Laurel Road, Athens, TX
75751. Telephone: (903) 675-6825. Fax: (903) 675-6823.
Web site: www.myositissupportgroup.org/
2562

Myotonic dystrophy
Definition
Myotonic dystrophy is a progressive disease in
which the muscles are weak and are slow to relax
after contraction.

Description
Myotonic dystrophy (DM), also called dystrophia
myotonica, myotonia atrophica, or Steinert’s disease,
is a common form of muscular dystrophy. DM is an
inherited disease, affecting males and females approximately equally. About 30,000 people in the United
States are affected. Symptoms may appear at any
time from infancy to adulthood. DM causes general
weakness, usually beginning in the muscles of the
hands, feet, neck, or face. It slowly progresses to
involve other muscle groups, including the heart.
DM affects a wide variety of other organ systems as
well.
A severe form of DM, congenital myotonic dystrophy or Thomsen’s disease, may appear in newborns
of mothers who have DM. Congenital means that the
condition is present from birth. The incidence of congenital myotonic dystrophy is thought to be about
1:20,000.
DM occurs in about 1 per 7,000–8,000 people and
has been described in people from all over the world.

Causes and symptoms
The most common type of DM is called DM1 and
is caused by a mutation in a gene called myotonic
GALE ENCYCLOPEDIA OF MEDICINE

Some families with symptoms of DM do not have
a mutation in the DMPK gene. As of early 2001,
scientists have found that the DM in many of these
families is caused by a mutation in a gene on chromosome 3. These families are said to have DM2.
Congenital myotonic dystrophy has been linked
to a region on chromosome 7 that contains a muscle
chloride channel gene.
Trinucleotide repeats
In the DMPK gene, there is a section of the genetic
code called a CTG repeat. The letters stand for three
nucleotides (complex organic molecules) known as
cytosine, thymine, and guanine, and are repeated a
certain number of times. In people who have DM1,
this sequence of nucleotides is repeated too many
times—more than the normal number of 37 times—
and thus this section of the gene is too big. This
enlarged section of the gene is called a trinucleotide
repeat expansion.
People who have repeat numbers in the normal
range will not develop DM1 and cannot pass it to their
children. Having more than 50 repeats causes DM1.
People who have 38–49 repeats have a premutation
and will not develop DM1, but can pass DM1 onto
their children. Having repeats numbers greater than
1000 causes congenital myotonic dystrophy.
In general, the more repeats in the affected range
that someone has, the earlier the age of onset of symptoms and the more severe the symptoms. However,
this is a general rule. It is not possible to look at a
person’s repeat number and predict at what age they
will begin to have symptoms or how their condition
will progress.
Exactly how the trinucleotide repeat expansion
causes myotonia, the inability to relax muscles, is not
yet understood. The disease somehow blocks the flow
of electrical impulses across the muscle cell membrane.
Without proper flow of charged particles, the muscle
cannot return to its relaxed state after it has
contracted.
Since 2001 it has been discovered that DM2 is
caused by a CCTG (cytosine-cytosine-thymine-guanine) expansion on chromosome 3 at locus 3q21, but
as of 2004 it is not known how this repeat affects
muscle cell function.
GALE ENCYCLOPEDIA OF MEDICINE

Anticipation
Sometimes when a person who has repeat numbers in the affected or premutation range has children,
the expansion grows larger. This is called anticipation.
A larger expansion can result in an earlier age of onset
in children than in their affected parent. Anticipation
happens more often when a mother passes DM1 onto
her children then when it is passed from the father.
Occasionally repeat sizes stay the same or even get
smaller when they are passed to a person’s children.
Inheritance
DM is inherited through autosomal dominant
inheritance. This means that equal numbers of males
and females are affected. It also means that only one
gene in the pair needs to have the mutation in order for
a person to be affected. Since a person only passes one
copy of each gene onto their children, there is a 50% or
one in two chance that a person who has DM will pass
it onto each of their children. This percentage is not
changed by results of other pregnancies. A person with
a premutation also has a 50%, or one in two, chance of
passing the altered gene on to each of their children.
However, whether or not their children will develop
DM1 depends on whether the trinucleotide repeat
becomes further expanded. A person who has repeat
numbers in the normal range cannot pass DM1 onto
their children.
There is a range in the severity of symptoms in
DM and not everyone will have all of the symptoms
listed here.
Myotonic dystrophy causes weakness and delayed
muscle relaxation called myotonia. Symptoms of DM
include facial weakness and a slack jaw, drooping eyelids called ptosis, and muscle wasting in the forearms
and calves. A person with DM has difficulty relaxing
his or her grasp, especially in the cold. DM affects the
heart muscle, causing irregularities in the heartbeat. It
also affects the muscles of the digestive system, causing
constipation and other digestive problems. DM may
cause cataracts, retinal degeneration, low IQ, frontal
balding, skin disorders, atrophy of the testicles, and
diabetes. It can also cause sleep apnea—a condition in
which normal breathing is interrupted during sleep.
DM increases the need for sleep and decreases motivation. Severe disabilities do not set in until about 20
years after symptoms begin. Most people with myotonic dystrophy maintain the ability to walk, even late
in life.
A severe form of DM, congenital myotonic dystrophy, may appear in newborns of mothers who have
DM1. Congenital myotonic dystrophy is marked by
2563

Myotonic dystrophy

dystrophy protein kinase (DMPK). The DMPK gene
is located on chromosome 19q. When there is a mutation in this gene, a person develops DM1. The specific
mutation that causes DM1 is called a trinucleotide
repeat expansion.

Myotonic dystrophy

severe weakness, poor sucking and swallowing
responses, respiratory difficulty, delayed motor development, and mental retardation. Death in infancy is
common in this type.
Some people who have a trinucleotide repeat
expansion in their DMPK gene do not have symptoms
or have very mild symptoms that go unnoticed. It is
not unusual for a woman to be diagnosed with DM
after she has an infant with congenital myotonic
dystrophy.
Predictive testing
It is possible to test someone who is at risk for
developing DM1 before they are showing symptoms
to see whether they inherited an expanded trinucleotide repeat. This is called predictive testing. Predictive
testing cannot determine the age of onset that someone will begin to have symptoms, or the course of the
disease.

Diagnosis
Diagnosis of DM is not difficult once the disease is
considered. However, the true problem may be
masked because symptoms can begin at any age, can
be mild or severe, and can occur with a wide variety of
associated complaints. Diagnosis of DM begins with a
careful medical history and a thorough physical exam
to determine the distribution of symptoms and to rule
out other causes. A family history of DM or unexplained weakness helps to establish the diagnosis.
A definitive diagnosis of DM1 is done by genetic
testing, usually by taking a small amount of blood.
The DNA in the blood cells is examined and the
number of repeats in the DMPK gene is determined.
Various other tests may be done to help establish the
diagnosis, but only rarely would other testing be
needed. An electromyogram (EMG) is a test is used
to examine the response of the muscles to stimulation.
Characteristic changes are seen in DM that helps distinguish it from other muscle diseases. Removing a
small piece of muscle tissue for microscopic examination is called a muscle biopsy. DM is marked by characteristic changes in the structure of muscle cells that
can be seen on a muscle biopsy. An electrocardiogram
could be performed to detect characteristic abnormalities in heart rhythm associated with DM. These symptoms often appear later in the course of the disease.
Prenatal testing
Testing a pregnancy to determine whether an
unborn child is affected is possible if genetic testing
2564

in a family has identified a DMPK mutation. This can
be done at 10–12 weeks gestation by a procedure called
chorionic villus sampling (CVS) that involves removing
a tiny piece of the placenta and analyzing DNA from
its cells. It can also be done by amniocentesis after 14
weeks gestation by removing a small amount of the
amniotic fluid surrounding the baby and analyzing the
cells in the fluid. Each of these procedures has a small
risk of miscarriage associated with it and those who
are interested in learning more should check with their
doctor or genetic counselor.
There is also another procedure called preimplantation diagnosis that allows a couple to have a child
that is unaffected with the genetic condition in their
family. This procedure is experimental and not widely
available. Those interested in learning more about this
procedure should check with their doctor or genetic
counselor.
A group of researchers in Houston, Texas,
reported in 2004 that they have successfully developed
a technique for detecting the CCTG expansion that
causes DM2 and estimating the size of the repeat
expansion.

Treatment
Myotonic dystrophy cannot be cured, and no
treatment can delay its progression. As of the early
2000s there is no standardized treatment for these
disorders because the precise reasons for muscle weakness are not yet fully understood. However, many of
the symptoms can be treated. Physical therapy can
help preserve or increase strength and flexibility in
muscles. Ankle and wrist braces can be used to support weakened limbs. Occupational therapy is used to
develop tools and techniques to compensate for loss of
strength and dexterity. A speech-language pathologist
can provide retraining for weakness in the muscles
controlling speech and swallowing.
Irregularities in the heartbeat may be treated with
medication or a pacemaker. A yearly electrocardiogram is usually recommended to monitor the heartbeat. Diabetes mellitus in DM is treated in the same
way that it is in the general population. A high-fiber
diet can help prevent constipation. Sleep apnea may be
treated with surgical procedures to open the airways
or with nighttime ventilation. Treatment of sleep
apnea may reduce drowsiness. Lens replacement surgery is available when cataracts develop. Pregnant
woman should be followed by an obstetrician familiar
with the particular problems of DM because complications can occur during pregnancy, labor and
delivery.
GALE ENCYCLOPEDIA OF MEDICINE

Electrocardiogram (ECG, EKG)—A test that uses
electrodes attached to the chest with an adhesive
gel to transmit the electrical impulses of the heart
muscle to a recording device.
Electromyography (EMG)—A test that uses electrodes to record the electrical activity of muscle. The
information gathered is used to diagnose neuromuscular disorders.
Muscular dystrophy—A group of inherited diseases characterized by progressive wasting of the
muscles.
Nucleotide—Any of a group of organic molecules
that link together to form the building blocks of
DNA or RNA.
Sleep apnea—Temporary cessation of breathing
while sleeping.
Trinucleotide repeat expansion—A sequence of
three nucleotides that is repeated too many times
in a section of a gene.

Meola, G., and V. Sansone. ‘‘Treatment in Myotonia and
Periodic Paralysis.’’ Revue neurologique (Paris) 160,
no. 5, Part 2 (May 2004: S55–S69.
Meola, Giovanni. ‘‘Myotonic Dystrophies.’’ Current
Opinion in Neurology 13 (2000): 519–525.
Ranum, L. P., and J. W. Day. ‘‘Myotonic dystrophy: RNA
Pathogenesis Comes into Focus.’’ American Journal of
Human Genetics 74 (May 2004): 793–804.
Sallinen, R., A. Vihola, L. L. Bachinski, et al. ‘‘New
Methods for Molecular Diagnosis and Demonstration
of the (CCTG)n Mutation in Myotonic Dystrophy
Type 2 (DM2).’’ Neuromuscular Disorders 14 (April
2004): 274–283.
ORGANIZATIONS

Muscular Dystrophy Association. 3300 East Sunrise Dr.,
Tucson, AZ 85718. (520) 529-2000 or (800) 572-1717.
<http://www.mdausa.org>.
OTHER

Gene Clinics. <http://www.geneclinics.org>.
Myotonic Dystrophy Website. <http://www.umd
.necker.fr/myotonic_dystrophy.html>.
NCBI Genes and Disease Web Page. <http://
www.ncbi.nlm.nih.gov/disease/Myotonic.html>.

Karen M. Krajewski, M.S., C.G.C.
Rebecca J. Frey, Ph.D.
Wearing a medical bracelet is advisable. Some
emergency medications may have dangerous effects
on the heart rhythm in a person with DM. Adverse
reactions to general anesthesia may also occur.

Myringotomy and ear tubes
Prognosis

Definition

The course of myotonic dystrophy varies. When
symptoms appear earlier in life, disability tends to
become more severe. Occasionally people with DM
may require a wheelchair later in life. Children with
congenital DM usually require special educational
programs and physical and occupational therapy.
For both types of DM, respiratory infections pose a
danger when weakness becomes severe.

Myringotomy is a surgical procedure in which a
small incision is made in the eardrum (the tympanic
membrane), usually in both ears. The word comes
from myringa, modern Latin for drum membrane,
and tom
e, Greek for cutting. It is also called myringocentesis, tympanotomy, tympanostomy, or paracentesis of the tympanic membrane. Fluid in the middle ear
can be sucked out through the incision.

Resources

Ear tubes, or tympanostomy tubes, are small tubes,
open at both ends, that are inserted into the incisions in
the eardrums during myringotomy. They come in various shapes and sizes and are made of plastic, metal, or
both. They are left in place until they fall out by themselves or until they are removed by a doctor.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Myotonic Disorders.’’ Section 14, Chapter 184. In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

International Myotonic Dystrophy Consortium (IMDC).
‘‘New Nomenclature and DNA Testing Guidelines for
Myotonic Dystrophy Type 1 (DM1).’’ Neurology 54
(2000): 1218–1221.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
Myringotomy with the insertion of ear tubes is an
optional treatment for inflammation of the middle ear
with fluid collection (effusion), also called glue ear, that
2565

Myringotomy and ear tubes

KEY TERMS

Myringotomy and ear tubes

lasts more than three months (chronic otitis media with
effusion) and does not respond to drug treatment. It is
the recommended treatment if the condition lasts four
to six months. Effusion is the collection of fluid that
escapes from blood vessels or the lymphatic system. In
this case, the fluid collects in the middle ear.
Initially, acute inflammation of the middle ear with
effusion is treated with one or two courses of antibiotics.
Antihistamines and decongestants have been used, but
they have not been proven effective unless there is also
hay fever or some other allergic inflammation that
contributes to the problem. Myringotomy with or without the insertion of ear tubes is NOT recommended for
initial treatment of otherwise healthy children with
middle ear inflammation with effusion.
In about 10% of children, the effusion lasts for
three months or longer, when the disease is considered
chronic. In children with chronic disease, systemic
steroids may help, but the evidence is not clear, and
there are risks.
When medical treatment does not stop the effusion after three months in a child who is one to three
years old, is otherwise healthy, and has hearing loss in
both ears, myringotomy with insertion of ear tubes
becomes an option. If the effusion lasts for four to
six months, myringotomy with insertion of ear tubes is
recommended.
The purpose of myringotomy is to relieve symptoms, to restore hearing, to take a sample of the fluid
to examine in the laboratory in order to identify any
microorganisms present, or to insert ear tubes.
Ear tubes can be inserted into the incision during
myringotomy and left there. The eardrum heals around
them, securing them in place. They usually fall out on
their own in 6-12 months or are removed by a doctor.
While they are in place, they keep the incision
from closing, keeping a channel open between the
middle ear and the outer ear. This allows fresh air to
reach the middle ear, allowing fluid to drain out, and
preventing pressure from building up in the middle
ear. The patient’s hearing returns to normal immediately and the risk of recurrence diminishes.
Parents often report that children talk better, hear
better, are less irritable, sleep better, and behave better
after myringotomy with the insertion of ear tubes.

Description
The procedure is usually done in an ambulatory
surgical unit under general anesthesia, although some
physicians do it in the office with sedation and local
2566

anesthesia, especially in older children. The ear is
washed, a small incision made in the eardrum, the
fluid sucked out, a tube inserted, and the ear packed
with cotton to control bleeding.
There has been an effort to design ear tubes that
are easier to insert or to remove, and to design tubes
that stay in place longer. Therefore, ear tubes come in
various shapes and sizes.

Preparation
The child may not have food or water for four to
six hours before anesthesia. Antibiotics are usually not
needed.

Aftercare
Use of antimicrobial drops is controversial. Water
should be kept out of the ear canal until the eardrum is
intact. A doctor should be notified if the tubes fall out.

Risks
The risks include:


Cutting the outer ear



Formation at the myringotomy site of granular
nodes due to inflammation



Formation of a mass of skin cells and cholesterol in
the middle ear that can grow and damage surrounding bone (cholesteatoma)



Permanent perforation of the eardrum.

The risk of persistent discharge from the ear (otorrhea) is 13%.
If the procedure is repeated, structural changes in
the eardrum can occur, such as loss of tone (flaccidity),
shrinkage or retraction, or hardening of a spot on the
eardrum (typmanosclerosis). The risk of hardening is
51%; its effects on hearing are not known, but they are
probably insignificant.
It is possible that the incision will not heal properly, leaving a permanent hole in the eardrum, which
can cause some hearing loss and increases the risk of
infection.
It is also possible that the ear tube will move
inward and get trapped in the middle ear, rather than
move out into the external ear, where it either falls out
on its own or can be retrieved by a doctor. The exact
incidence of tubes moving inward is not known, but it
could increase the risk of further episodes of middleear inflammation, inflammation of the eardrum or the
part of the skull directly behind the ear, formation of a
GALE ENCYCLOPEDIA OF MEDICINE

Myringotomy and ear tubes

Eustachian tube

Ear drum

Tube

The insertion of ear tubes in the eardrum helps to alleviate chronic middle ear infections. (Illustration by Argosy, Inc.)

mass in the middle ear, or infection due to the presence
of a foreign body.
The surgery may not be a permanent cure. As
many as 30% of children undergoing myringotomy
with insertion of ear tubes need to undergo another
procedure within five years.
The other risks include those associated with sedatives or general anesthesia.
An additional element of post-operative care is
the recommendation by many doctors that the child
use ear plugs to keep water out of the ear during
bathing or swimming, to reduce the risk of infection
and discharge.
Resources
BOOKS

Lim, David J., et al., editors. Recent Advances in Otitis Media:
Proceedings of the Sixth International Symposium, June
4-8, 1995, Marriott Harbot Beach, Ft. Lauderdale,
Florida. Hamilton, Ontario: B. C. Decker Inc., 1996.

Mary Zoll, PhD

KEY TERMS
Acute otitis media—Inflammation of the middle
ear with signs of infection lasting less than three
months.
Chronic otitis media—Inflammation of the middle
ear with signs of infection lasting three months or
longer.
Effusion—The escape of fluid from blood vessels or
the lymphatic system and its collection in a cavity,
in this case, the middle ear.
Middle ear—The cavity or space between the eardrum and the inner ear. It includes the eardrum, the
three little bones (hammer, anvil, and stirrup) that
transmit sound to the inner ear, and the eustachian
tube, which connects the inner ear to the nasopharynx (the back of the nose).
Tympanic membrane—The eardrum. A thin disc of
tissue that separates the outer ear from the middle
ear.
Tympanostomy tube—Ear tube. A small tube made
of metal or plastic that is inserted during myringotomy to ventilate the middle ear.

Myxedema see Hypothyroidism
GALE ENCYCLOPEDIA OF MEDICINE

2567

Myxoma

KEY TERMS

Myxoma
Definition
A myxoma is a rare, usually noncancerous, primary tumor (a new growth of tissue) of the heart. It is
the most common of all benign heart tumors.

Description
Myxoma is an intracardiac tumor; it is found
inside the heart. Seventy five percent of all myxomas
are found in the left atrium, and almost all other
myxomas are found in the right atrium. It is very
rare for a myxoma to be found in either of the ventricles. The tumor takes one of two general shapes: a
round, firm mass, or an irregular shaped, soft, gelatinous mass. They are attached to the endocardium, the
inside lining of the heart. The cells that make up the
tumor are spindle-shaped cells and are embedded in a
matrix rich in mucopolysaccharides (a group of carbohydrates). Myxomas may contain calcium, which
shows up on x rays. The tumor gets its blood supply
from capillaries that bring blood from the heart to the
tumor. Thrombi (blood clots) may be attached to the
outside of the myxoma.
There are three major syndromes linked to myxomas: embolic events, obstruction of blood flow, and
constitutional syndromes. Embolic events happen
when fragments of the tumor, or the thrombi attached
to the outside of the tumor, are released and enter the
blood stream. Gelatinous myxomas are more likely to
embolize than the more firm form of this tumor.
Myxomas may also obstruct blood flow in the
heart, usually at a heart valve. The mitral valve is the
heart valve most commonly affected. Blood flow
restrictions can lead to pulmonary congestion and
heart valve disease. Embolization can lead to severe
consequences. In cases of left atrial myxoma, 40-50%
of patients experience embolization. Emboli usually
end up in the brain, kidneys, and extremities.
The third syndrome linked to myxomas are called
constitutional syndromes, nonspecific symptoms
caused by the myxoma.

Causes and symptoms
There is no known causative agent for myxoma.
The main symptoms, if any, produced by myxoma are

2568

Embolus—A piece of tissue, blood clot, etc. that
travels through the blood system and can lodge in
smaller blood vessels anywhere in the body.
Metastasis—The spread of a cancer or infectious
agent from the site of origin to other areas of the
body.
Raynaud’s phenomenon—Intermittant ischemia
(deficient blood flow) of the fingers or toes, sometimes also affecting the ears and nose.

generic and not specific. These include fever, weight
loss, anemia, elevated white blood cell (WBC) count,
decreased platelet count and Raynaud’s phenomenon.
Most patients with myxoma are between 30-60 years
of age.

Diagnosis
Diagnosis is made following a suspicion that a
myxoma might be present, and can usually be confirmed by echocardiogram

Treatment
Surgery is used to remove the tumor. Myxomas
can regrow if they are not completely removed. The
survival rate for this operation is excellent.

Prognosis
Successful removal of the tumor rids the patient of
this disease. Emboli from a myxoma may survive in
other areas of the body. However, there is no evidence
that myxoma is truly metastatic (able to transfer disease from one area to another), causing tumors in
other areas of the body.
Resources
OTHER

‘‘Myxoma, Intracardiac.’’ OMIM Home Page, Online
Mendelian Inheritance in Man. <http://
www.ncbi.nlm.nih.gov/Omim>.

John T. Lohr, PhD

GALE ENCYCLOPEDIA OF MEDICINE

N
Nail infections see Onychomycosis

Nail-patella syndrome
Definition
Nail-patella syndrome, is a genetic disease of the
connective tissue that produces defects in the fingernails, knee caps, and kidneys.

Description
Nail-patella syndrome is also known as Fong
Disease, Hereditary Onycho-Osteodysplasia (H.O.O.D.),
Iliac Horn Disease, and Turner-Kieser syndrome.
Patients who have nail-patella syndrome may show a
variety of physical defects. The hallmark features
of this syndrome are poorly developed fingernails, toenails, and patellae (kneecaps). Other common abnormalities include elbow deformities, abnormally shaped
pelvis bone (hip bone), and kidney (renal) disease.
Less common medical findings include defects of
the upper lip, the roof of the mouth, and unusual
skeletal abnormalities. Skeletal abnormalities may
include poorly developed scapulae (shoulder blades),
sideways bent fingers (clinodactyly), clubfoot, scoliosis, and unusual neck bones. There are also other
effects, such as thickening of the basement membrane
in the skin and of the tiny clusters of capillaries
(glomeruli) in the kidney. Scientists have recognized
an association between nail-patella syndrome and
colon cancer. Nail-patella syndrome is associated
with open-angle glaucoma, which, if untreated, may
lead to blindness. Patients may also have cataracts,
drooping eyelids (ptosis), or corneal problems such as
glaucoma.
People with nail-patella syndrome may display
only a few or many of the recognized signs of this
GALE ENCYCLOPEDIA OF MEDICINE

disease. Symptoms vary widely from person to person.
Signs even vary within a single family with multiple
affected members.
The incidence of nail-patella syndrome is approximately one in 50,000 births. This disorder affects
males and females equally. It is found throughout the
world and occurs in all ethnic groups. The strongest
risk factor for nail-patella syndrome is a family history
of the disease.

Causes and symptoms
Nail-patella syndrome has been recognized as an
inherited disorder for over 100 years. It is caused by
mutations in a gene known as LIM Homeobox
Transcription Factor 1-Beta (LMX1B), located on
the long arm of chromosome 9.
The LMX1B gene codes for a protein that is
important in organizing embryonic limb development.
Mutations in this gene have been detected in many
unrelated people with nail-patella syndrome.
Scientists have also been able to interrupt this gene in
mice to produce defects similar to those seen in human
nail-patella syndrome.
Nail-patella syndrome is inherited in an autosomal dominant manner. This means that possession of
only one copy of the defective gene is enough to cause
disease. When a parent has nail-patella syndrome each
of their children has a 50% chance to inherit the disease-causing mutation.
A new mutation causing nail-patella syndrome
can also occur, causing disease in a person with no
family history. This is called a sporadic occurrence and
accounts for approximately 20% of cases of nailpatella syndrome. The children of a person with sporadic nail-patella syndrome are also at a 50% risk of
developing signs of the disorder.
Medical signs of nail-patella syndrome vary
widely between patients. Some patients with this
2569

Nail-patella syndrome

disorder do not display symptoms. These patients are
discovered to have the nail-patella syndrome only
when genetic studies trace their family history.
Scientists are now working to learn what causes different people to display such different symptoms of
nail-patella syndrome.
The most obvious sign associated with nail-patella
syndrome is absent, poorly developed, or unusual fingernails. Fingernail abnormalities are found in over
80% of patients with this disorder. Abnormalities may
be found in one or more fingernails. Only rarely are all
fingernails affected. This disease most commonly
affects the fingernails of the thumbs and index fingers.
The pinky fingernail is least likely to be affected.
Fingernails may be small and concave with pitting,
ridges, splits, and/or discoloration. Toenails are less
often affected. The lunulae, or light-colored crescent
moons, at the base of the fingernail bed next to the
cuticle are sometimes triangularly-shaped in people
with nail-patella syndrome.
Kneecap abnormalities are the second most common sign associated with this disorder. Either or both
kneecaps may be missing or poorly formed. If present,
kneecaps are likely to be dislocated. The knees of
people with nail-patella syndrome may have a square
appearance. Besides the kneecap, other support structures including bones, ligaments, and tendons may
also be malformed. These support structures stabilize
the knee, therefore patients with some leg malformations may have difficulty in walking.
The hip bones of approximately 80% of patients
with nail-patella syndrome have unusual bony
projections called posterior iliac horns. These bony
projections, or spurs, are internal and not obvious
unless they are detected on x ray. This unusual pelvic
anatomy is not associated with any other disease.
Kidney disease is present in at least 30% of people
with nail-patella syndrome. Biopsy shows lesions that
resemble those of inflammation of the clusters of capillaries in the kidneys (glomerulonephritis), but without
any infection present. Kidney failure is the most dangerous consequence of nail-patella syndrome. It occurs
in about 30% of patients who have kidney involvement.
An early sign of kidney involvement is the presence of
protein or blood in the urine (chronic, benign proteinuria and hematuria.) Kidney involvement is progressive, so early diagnosis and treatment of renal disease
is important. Kidney disease has been reported in
children with nail-patella syndrome, but renal involvement more commonly develops during adulthood.
Various skeletal symptoms may occur. Patients
with nail-patella syndrome may not be able to fully
2570

straighten their arms at the elbow. This may create a
webbed appearance at the elbow joint. Patients may
have sideways bent fingers, poorly developed shoulder
blades, clubfoot, hip dislocation, unusual neck bones,
or scoliosis.
Eye problems may be present and vary from
person to person. Nail-patella syndrome is associated
with open angle glaucoma. Open angle glaucoma
is caused by fluid blocked into the front chamber of
the eye. This blocked fluid builds increasing pressure
into the eye. If untreated, this increased pressure
may lead to permanent damage of the optic nerve
and irreversible blindness. Some patients with nailpatella syndrome have ptosis, or drooping eyelids.
Nail-patella syndrome has also been associated
with abnormalities of the cornea, cataracts, and astigmatism. Additionally, the irises of the eye may be multicolored, possibly displaying a clover-shaped pattern of
color.

Diagnosis
As of early 2001, genetic testing for nail-patella
syndrome is available only through research institutions that are working to further characterize this
disorder. Genetic testing cannot predict which signs
of the disease will develop. Nor can genetic testing
predict the severity of disease symptoms. Improved
genetic testing for nail-patella syndrome is anticipated
in the future.
Diagnosis of this disease is most often made on
visual medical clues such as the characteristic abnormalities of the fingernails and kneecaps. Diagnosis is
confirmed by x-ray images of the affected bones and,
when indicated, kidney biopsy. The bony pelvic spurs
found in 80% of patients with nail-patella syndrome
are not associated with any other disease.
Prenatal diagnosis for nail-patella syndrome by
third-trimester ultrasound was documented in 1998.
Prenatal diagnosis via genetic testing of cells obtained
by chorionic villus sampling was reported the same
year. As of 2001, prenatal genetic testing for nailpatella syndrome is not yet widely available. There is
controversy surrounding the use of prenatal testing for
such a variable disorder. Prenatal testing cannot predict the extent of an individual’s disease.

Treatment
Treatment is usually not necessary. Treatment,
when required, depends on each patient’s specific
symptoms. Severe kidney disease is treated with dialysis or a kidney transplant. Patients receiving kidney
GALE ENCYCLOPEDIA OF MEDICINE

Chorionic villus sampling (CVS)—A procedure
used for prenatal diagnosis at 10–12 weeks gestation. Under ultrasound guidance a needle is
inserted either through the mother’s vagina or
abdominal wall and a sample of cells is collected
from around the early embryo. These cells are then
tested for chromosome abnormalities or other
genetic diseases.

Gene Clinics. <http://www.geneclinics.org>.
OMIM—Online Mendelian Inheritance in Man.
<http://www3.ncbi.nlm.nih.gov/Omim>.

John T. Lohr, PhD
Judy C. Hawkins, MS

Glomeruli—Tiny clusters of capillaries in the kidney.
Hematuria—The presence of blood in the urine.
Patella—The kneecap.
Proteinuria—Excess protein in the urine.

transplants do not develop nail-patella type renal
complications in their new kidney.
A wheelchair may be required if walking becomes
painful due to bone, tendon, ligament, or muscle
defects. Orthopedic surgery may be necessary for congenital clubfoot deformity. Manipulation or surgery
may be required to correct hip dislocation. Cataracts
are also surgically treated. Medical treatment at early
signs of glaucoma prevents progression of the disease
to blindness.
Genetic counseling is offered to persons who have
the disease. Parents with this disease have a 50% chance
of passing it to each of their children. As of 2001,
current genetic testing technology cannot predict the
severity or scope of an individual’s symptoms.
Because many possible manifestations of nailpatella syndrome exist, patients are advised to pursue
extra medical care including regular urinalysis and
special eye exams. Children with nail-patella syndrome
should be screened for scoliosis.

Nail removal
Definition
Nail removal is a form of treatment that is sometimes necessary following traumatic injuries or recurrent infections in the area of the nail. There are
nonsurgical as well as surgical methods of nail removal.

Purpose
Nails are removed only when necessary to allow
the skin beneath the nail (the nail bed) to heal or in
some cases, to remove a nail that has been partially
pulled out in an accident. In the case of toenails, it is
occasionally necessary to remove the nail of the large
toe due to a chronic condition caused by badly fitted
shoes. In general, however, doctors prefer to try other
forms of treatment before removing the nail.
Depending on the cause, nail disorders are usually
treated with oral medications; applying medicated
gels or creams directly to the skin around the nail;
avoiding substances that irritate the nail folds; surgical
lancing of abscesses around the nail; or injecting corticosteroids under the nail fold.
The most common causes of nail disorders include:


Trauma. The nails can be damaged by nail biting,
using the fingernails as tools, and incorrect use of
nail files and manicure scissors as well as by accidents
and sports injuries.



Infections. These include fungal infections under the
nails, bacterial infections of cuts or breaks in the nail
folds, or infections of the nails themselves caused by
Candida albicans. Inflammation of the nail folds is
called paronychia.



Exposure to harsh detergents, industrial chemicals,
hot water, and other irritants. People who work as
dishwashers are especially vulnerable to separation
of the nail itself from the nail bed (onycholysis).



Systemic diseases and disorders. These include
psoriasis, anemia, and certain congenital disorders.

Prognosis
Survival among patients with nail-patella syndrome is not decreased unless a they exhibit renal
complications. It is estimated that 8% of individuals
with nail-patella syndrome who come to medical
attention eventually die of kidney disease.
Resources
BOOKS

Berkow, R., M. H. Beers, A. J. Fletcher, and R. M. Bogin.
The Merck Manual of Medical Information - Home
Edition. McGraw-Hill, 2004.
GALE ENCYCLOPEDIA OF MEDICINE

Nail removal

OTHER

KEY TERMS

2571

Nail removal

Nail root
Lunula

Nail body

Hyponychium

Cuticle
Phalanx (bone)

The physiology of the human fingernail. The most common causes of nail disorders include trauma, infections, exposure to
harsh detergents, hot water and other irritants, systemic diseases and disorders, and allergic reactions to nail polish, nail polish
remover, and nail glue. (Illustration by Electronic Illustrators Group.)



Allergic reactions to nail polish, polish remover, or
the glue used to attach false nails.

Precautions
In the case of infections, it is necessary to distinguish between fungal, bacterial, and candidal infections
before removing the nail. Cultures can usually be
obtained from pus or tissue fluid from the affected nail.

Description
Surgical nail removal
If necessary, the surgeon can remove the nail at its
base with an instrument called a needlepoint scalpel.
In a few cases, the nail may need to be pulled out
(avulsed) from its matrix.
Nonsurgical nail removal
Nails can be removed by applying a mixture of
40% urea, 20% anhydrous lanolin, 5% white wax,
25% white petroleum jelly, and silica gel type H.

KEY TERMS
Avulse—To pull or tear away forcibly. In some
cases, a surgeon must remove a nail by avulsing it
from its matrix.
Matrix—The tissue at the base of the nail, from
which the nail grows.
Nail bed—The layer of tissue underneath the nail.
Onycholysis—The separation of a nail from its
underlying bed. Onycholysis is a common symptom of candidal infections of the nail or of exposure
to harsh chemicals and detergents.
Paronychia—Inflammation of the folds of skin that
surround a nail.

the urea mixture, followed by a layer of plastic film
and adhesive tape. The mixture is left on the nail for
five to 10 days, after which the nail itself can be
removed.

Aftercare
Preparation
For nonsurgical nail removal, the nail fold is
treated with tincture of benzoin and covered with
adhesive tape. The nail itself is thickly coated with
2572

Aftercare of surgical removal is similar to the care
of any minor surgical procedure. Aftercare of the urea
paste method includes applying medication for the
specific infection that is being treated.
GALE ENCYCLOPEDIA OF MEDICINE

Risks from either procedure are minimal.

Normal results
Normal results include the successful removal of
the infected or damaged nail.
Resources
BOOKS

Baden, Howard P. ‘‘Diseases of the Nails.’’ In Conn’s
Current Therapy, 1996, edited by Robert E. Rakel.
Philadelphia: W. B. Saunders Co., 1996.

Rebecca J. Frey, PhD

Nalidixic acid see Urinary anti-infectives
Narcissistic personality disorder see
Personality disorders

Narcolepsy
Definition
Narcolepsy is a disorder marked by excessive
daytime sleepiness, uncontrollable sleep attacks, and
cataplexy (a sudden loss of muscle tone, usually lasting
up to half an hour).

Description
Narcolepsy is the second-leading cause of excessive daytime sleepiness (after obstructive sleep apnea).
Persistent sleepiness and sleep attacks are the hallmarks of this condition. The sleepiness has been compared to the feeling of trying to stay awake after not
sleeping for two or three days.
People with narcolepsy fall asleep suddenly—
anywhere, at any time, maybe even in the middle of
a conversation. These sleep attacks can last from a
few seconds to more than an hour. Depending on
where they occur, they may be mildly inconvenient
or even dangerous to the individual. Some people
continue to function outwardly during the sleep
episodes, such as talking or putting things away.
But when they wake up, they have no memory of
the event.
Narcolepsy is related to the deep, dreaming
part of sleep known as rapid eye movement (REM)
sleep. Normally when people fall asleep, they
GALE ENCYCLOPEDIA OF MEDICINE

experience 90 minutes of non-REM sleep, which is
then followed by REM sleep. People with narcolepsy,
however, enter REM sleep immediately. In addition,
REM sleep occurs inappropriately throughout
the day.
There has been debate over the incidence of narcolepsy. It is thought to affect between one in every
1,000 to 2,000 Americans. The known prevalence in
other countries varies, from one in 600 in Japan to one
in 500,000 in Israel. Reasons for these differences are
not clear.

Causes and symptoms
In 1999 researchers identified the gene that causes
narcolepsy. The gene allows cells in the hypothalamus
(the part of the brain that regulates sleep behavior) to
receive messages from other cells. When this gene is
abnormal, cells cannot communicate properly, and
abnormal sleeping patterns develop.
The disorder sometimes runs in families, but most
people with narcolepsy have no relatives with the
disorder. Researchers believe that the inheritance of
narcolepsy is similar to that of heart disease. In heart
disease, several genes play a role in being susceptible to
the disorder, but it usually does not develop without
an environmental trigger of some sort.
While the symptoms of narcolepsy usually appear
during the teens or 20s, the disease may not be diagnosed for many years. Most often, the first symptom is
an overwhelming feeling of fatigue. After several
months or years, cataplexy and other symptoms
appear.
Cataplexy is the most dramatic symptom of narcolepsy. It affects 75% of people with the disorder.
During attacks, the knees buckle and the neck muscles
go slack. In extreme cases, the person may become
paralyzed and fall to the floor. This loss of muscle
tone is temporary, lasting from a few seconds to half
an hour, but frightening. The attacks can occur at any
time but are often triggered by strong emotions, such
as anger, joy, or surprise.
Other symptoms of narcolepsy include:


sleep attacks: short, uncontrollable sleep episodes
throughout the day



sleep paralysis: a frightening inability to move
shortly after awakening or dozing off



auditory or visual hallucinations: intense, sometimes
terrifying experiences at the beginning or end of a
sleep period
2573

Narcolepsy

Risks

Narcolepsy



disturbed nighttime sleep: tossing and turning, nightmares, and frequent awakenings during the night

Diagnosis
If a person experiences both excessive daytime sleepiness and cataplexy, a diagnosis may be made on the
patient history alone. Laboratory tests, however, can
confirm a diagnosis. These may include an overnight
polysomnogram—a test in which sleep is monitored
with electrocardiography, video, and respiratory parameters. A Multiple Sleep Latency Test, which measures
sleep latency (onset) and how quickly REM sleep
occurs, may be used. People who have narcolepsy
usually fall asleep in less than five minutes.
If a diagnosis is in question, a genetic blood test
can reveal the existence of certain substances in people
who have a tendency to develop narcolepsy. Positive
test results suggest, but do not prove, the existence of
narcolepsy.
Narcolepsy is a complex disorder, and it is often
misdiagnosed. It takes 14 years, on average, for an
individual to be correctly diagnosed.

Treatment
There is no cure for narcolepsy. It is not progressive, and it is not fatal, but it is chronic. The symptoms
can be managed with medication or lifestyle adjustment. Amphetamine-like stimulant drugs are often
prescribed to control drowsiness and sleep attacks. A
drug called sodium oxybate (Xyrem) was tested for
use in 2004 and was shown to reduce daytime sleepiness as well as cataplexy attacks when used along
with stimulants. Patients who do not like taking
high doses of stimulants may choose to take smaller
doses and ‘‘manage’’ their lifestyles, such as by
napping every few hours to relieve daytime sleepiness.
Antidepressants are often effective in treating symptoms of abnormal REM sleep.
With the recent discovery of the gene that causes
narcolepsy, researchers are hopeful that therapies can
be designed to relieve the symptoms of the disorder.

Prognosis
Narcolepsy is not a degenerative disease, and
patients do not develop other neurologic symptoms.
However, narcolepsy can interfere with a person’s
ability to work, play, drive, and perform other daily
activities. In severe cases, the disorder prevents people
from living a normal life, leading to depression and a
loss of independence.
2574

KEY TERMS
Cataplexy—A symptom of narcolepsy in which
there is a sudden episode of muscle weakness triggered by emotions. The muscle weakness may
cause the person’s knees to buckle, or the head to
drop. In severe cases, the patient may become
paralyzed for a few seconds to minutes.
Hypnagogic hallucinations—Dream-like auditory
or visual hallucinations that occur while falling
asleep.
Hypothalamus—A part of the forebrain that controls heartbeat, body temperature, thirst, hunger,
body temperature and pressure, blood sugar levels,
and other functions.
Sleep paralysis—An abnormal episode of sleep in
which the patient cannot move for a few minutes,
usually occurring on falling asleep or waking up.
Often found in patients with narcolepsy.

Resources
PERIODICALS

Siegel, Jeremy M. ‘‘Narcolepsy.’’ Scientific American
January 2000. <http://www.sciam.com/2000/
0100issue/0100siegel.html>.
‘‘Xyrem Study for EDS in Narcolepsy Shows Positive Data
Across All Measures.’’ Pain & Central Nervous System
Week January 14, 2004: 69.
ORGANIZATIONS

American Sleep Disorders Association. 1610 14th St. NW,
Suite 300, Rochester, MN 55901. (507) 287-6006.
Narcolepsy Network. PO Box 42460, Cincinnati, OH 45242.
(973) 276- 0115.
National Center on Sleep Disorders Research. Two
Rockledge Centre, 6701 Rockledge Dr., Bethesda,
MD 20892. (301) 435-0199.
National Sleep Foundation. 1522 K St., NW, Suite 500,
Washington, DC 20005. (202) 785-2300.
<http://www.sleepfoundation.org>.
Stanford Center for Narcolepsy. 1201 Welch Rd-Rm P-112,
Stanford, CA 94305. (415) 725-6517.
University of Illinois Center for Narcolepsy Research. 845 S.
Damen Ave., Chicago, IL 60612. (312) 996-5176.
OTHER

‘‘Stanford Researchers Nab Narcolepsy Gene For
SleepDisorders.’’ Stanford University Medical Center.
[cited August 5, 1999]. <http://www.stanford.edu/
%7Edement/ngene.html>.

Michelle Lee Brandt
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Narcotics are natural opioid drugs derived from
the Asian poppy Palaver somniferous or semi-synthetic
or synthetic substitutes for these drugs.

Purpose
Narcotics are drugs that dull the sense of pain and
cause drowsiness or sleep. They are the most effective
tool a physician has to relieve severe pain. Narcotics
are also given pre-operatively to relieve anxiety and
induce anesthesia. Other common uses are to suppress
cough and to control very severe diarrhea. In large
doses, they can suppress the ability to breathe and
cause coma and death. Narcotics are also taken illegally for recreational use.

Precautions
Narcotics should only be taken under the direction of a physician. These drugs depress the central
nervous system and should not be taken with other
drugs, such as alcohol, barbiturates, antihistamines,
and benzodiazepines that also depress the central
nervous system.
Opioids are broken down by the liver. Individuals
with liver damage may not detoxify these substances
as rapidly as healthy individuals, leading to potential
accidental overdose. Street narcotics are of uncertain
strength and may be contaminated with toxic chemicals or contain a mixture of drugs that can cause
life-threatening reactions.

Description
Natural narcotics are derived directly from the
sap of the unripe seed pods of the opium poppy.
Morphine and codeine are the most familiar natural
narcotics and are the narcotics most frequently used in
medical settings. Often they are prescribed in combination with other non-narcotic drugs. Heroin is a
semi-synthetic narcotic. It has no medical or legal
uses. Other completely synthetic narcotics are made
in the laboratory. These include drugs with medical
uses such as fentanyl and oxycodone and illegal
‘‘designer drugs’’ synthesized for recreational use.
Some man-made narcotics are hundreds of times
more potent than natural narcotics.
Narcotics depress the central nervous system.
They work by binding chemically with receptors in a
GALE ENCYCLOPEDIA OF MEDICINE

Morphine (Roxanol, Dura morphine, morphine
sulfate, morphine hydrochloride) is the most commonly used medical narcotic for managing moderate
to severe pain. It can be also be used to control extreme
diarrhea caused by cholera or similar diseases.
Morphine sulfate is a white powder that dissolves in
water. It is usually given by injection into a muscle or
intravenously by injection into a vein. When given
intravenously, its effect occurs almost immediately.
Individuals given morphine regularly have a high
potential for developing dependence on the drug.
Morphine can cause withdrawal symptoms if stopped
abruptly. It is not a common street drug.
More codeine is prescribed medically than any
other narcotic. Concentrations of codeine in the sap
of the opium poppy are low, so most codeine is manufactured by chemical alteration of morphine. For pain
control, codeine is combined with other non-narcotic
painkillers such as aspirin (Empirin with Codeine,)
acetaminophen (Tylenol with Codeine) or non-steroid
anti-inflammatory drugs. These combination painkillers are manufactured as tablets (most common) or
liquids and come in a variety of strengths based on the
amount of codeine they contain. Codeine is also found
in some cough syrups (Robitussin A-C, for example)
and is used to control dry cough. Occasionally codeine
is used to control severe diarrhea, although diphenoxylate (Lomotil) is used more often.
In Canada, certain low-dose codeine pain relievers are sold without prescription. In the United
States pain medication with codeine requires a prescription. The likelihood of physical or psychological
dependence on codeine is much lower than with
morphine.
Hydromorphone (Dilaudid) is a narcotic synthetically produced from morphine. It is available in
tablets or as an injectable solution and used for pain
relief. It is one of the most common pain relievers
prescribed for patients who are terminally ill, because
it combines high effectiveness with low side effects.
Mederidine (Demerol) was originally developed
to treat muscle spasms but is as of 2005 used mainly
for pain relief. It is manufactured as tablets of varying
strengths. Another synthetic pain relief narcotic whose
use parallels mederidine is propoxyphene. When combined with aspirin this narcotic is known under the
brand name Darvon.
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Narcotics

Narcotics

way that blocks the transmission of nerve impulses.
These drugs do not cure the source of the pain; they
simply block the individual’s perception of pain.
When used to treat cough or diarrhea, they slow or
block muscle contractions.

Narcotics

Oxycodone (Oxycontin), a synthetic narcotic used
for pain relief, is manufactured both alone and with
aspirin (Percodan) or acetaminophen (Percoset) in
tablets of various strengths. OxyContin is a controlled
release formula of oxycodone that controls pain
continuously for 12 hours at a time. Oxycodone has
a high potential for prescription drug and street
abuse. Hydrocodone with acetaminophen (Vicodin)
is another synthetic narcotic whose use and potential
abuse parallels oxycodone.
Fentanyl (Sublimaze, Actiq, Duragesic) is used as
a surgical anesthetic. It is available as an injectable
solution and as a skin patch.
Methadone is a synthetic narcotic used mainly as
a substitute for heroin in heroin withdrawal treatment, although it does have pain-killing properties.
Methadone, when taken by mouth (liquid, wafers,
tablets) provides little of the euphoria of heroin, but
it blocks heroin cravings and withdrawal symptoms.
The first international attempts to control narcotic drugs were made in 1909 with the formation of the
Opium Commission Forum, which developed the
first international drug control treaty in 1912. In
the early 2000s narcotics are regulated internationally by the International Narcotics Control Board
(INCB), established in 1961. The INCB regulates the
cultivation of raw materials to make narcotics and
natural and man-made drugs. Cocaine and marijuana
also fall under the board’s control, although they are
not technically narcotics. Narcotic drugs are also
regulated by federal and state governments. In law
enforcement, the term narcotics is extended to include
other, mainly illicit drugs such as cocaine that have little
medical use.

Preparation
No special preparation is required before being
treated with narcotics, although, as with all medications, individuals should tell their physician about all
prescription and non-prescription drugs, supplements,
and herbal remedies that they are taking, as certain
medications may enhance the effects of narcotics.

Aftercare
When an individual is prescribed narcotics regularly for an extended period, tolerance may develop.
With tolerance, the individual must take higher
and higher doses to achieve the same level of pain
control. In some cases, when narcotics are stopped
abruptly, withdrawal symptoms may develop. These
include:
2576

KEY TERMS
Tapering—Gradually reducing the amount of a
drug when stopping it abruptly would cause
unpleasant withdrawal symptoms.



anxiety



irritability



rapid breathing



runny nose



sweating



vomiting and diarrhea



confusion



shaking



lack of appetite

In order to prevent withdrawal symptoms, the dose
of narcotics can be gradually diminished, a process
known as tapering, until they can be discontinued
completely without unpleasant effects. Individuals
may also be treated with the drug cloindine (Catapres)
to relieve some withdrawal symptoms.

Risks
All narcotics have the potential to become physically and psychologically addictive. When used regularly, tolerance can develop. Abuse and dependence
on narcotic prescription drugs in an increasing problem among the elderly particularly and among members of the middle class generally.
Overdose and withdrawal symptoms and reactions caused by contamination with other drugs or
toxic chemicals are common reasons for drug-related
visits to the emergency room by individuals using
street narcotics recreationally. Overdose is treated
with the drug naloxone (ReVia). Naloxone blocks
and reverses the effects of narcotics. When given intravenously it is effective within one to two minutes.

Normal results
When used as prescribed, narcotics are a generally
safe and effective way to relieve pain and control
cough and severe diarrhea. Individuals should not be
afraid they will develop an addiction after a short-term
course of narcotics following a dental or medical procedure, provided that they follow their physician’s
instructions for taking the drugs.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATION

National Institute on Drug Abuse/National Institutes of
Health. 6001 Executive Boulevard, Room 5213,
Bethesda, MD 20892-9561. (301) 443-1124.
<http://www.nida.nih.gov>.
United States Drug Enforcement Administration. Dr
Mailstop: AXS, 2401 Jefferson Davis Highway,
Alexandria, VA 22301. (202) 307-1000.
<http://www.dea.gov>.
OTHER

‘‘Narcotics.’’ United States Drug Enforcement
Administration (undated) [cited March 25, 2005]
<http://www.usdoj.gov/dea/concern/narcotics.html>.
National Institute on Drug Abuse. February 4, 2005 [cited
March 25, 2005]. <http://www.nida.nih.giv/Research
Report/Prescription/Prescription.html>
Stephens, Everett. Toxicity, Narcotics January 7, 2005 [cited
March 25, 2005]. <http://www.emedicine.com/emerg/
topic330.htm>.

Tish Davidson, A. M.

Nasal culture see Nasopharyngeal culture

Nasal irrigation
Definition
Nasal irrigation is the practice of flushing the
nasal cavity with a sterile solution. The solution may
contain antibiotics or steroid medications.

Purpose
Nasal irrigation is used to clear infected sinuses
or may be performed after surgery to the nose region.
It may be performed by adding antibiotics to the
solution to treat nasal polyps, nasal septal deviation,
allergic nasal inflammation, chronic sinus infection,
and swollen mucous membranes. One benefit of
nasal irrigation in treating these conditions is that it
usually lowers the amount of medication that the
patient must take by mouth.
Irrigation is also used to treat long-term users of
inhalants, such as illicit drugs (cocaine), or such occupational toxins as paint fumes, sawdust, pesticides,
and coal dust.
Nasal irrigation may also be used in occupational
medicine to monitor workers for exposure to airborne
glass fibers, asbestos, and similar materials.
GALE ENCYCLOPEDIA OF MEDICINE

Nasal irrigation should not be performed on people who have frequent nosebleeds; have recently had
nasal surgery; or whose gag reflex is impaired, as fluid
may enter the windpipe.

Description
Nasal irrigation can be performed by the
patient at home or by a medical professional. A
forced-flow instrument, such as a syringe, is filled
with a warm saline solution. The solution can be
commercially prepared (Ayr, NaSal) or can be prepared by the patient, using one half teaspoon salt
with each eight ounces of warm water. Occasionally,
antibiotics or steroids are added to the solution to
kill bacteria and aid healing of irritated membrane.
The syringe is then directed into the nostril. The
irrigation solution loosens encrusted material in
the nasal passage, and drainage takes place through
the nose. The patient leans over a catch basin
during irrigation, into which the debris flows.
Irrigation continues until all debris is cleared from
the passage. Nasal irrigation can be performed up
to twice daily, unless the irrigation irritates the
mucous membrane.

Preparation
Before nasal irrigation, the patient is instructed
not to open his or her mouth or swallow during the
procedure. Opening the mouth or swallowing may
cause infectious material to move from the nasal passage into the sinuses or the ear.

Risks
Complications of nasal irrigation include irritation of the nasal passages due to extreme temperature
of the irrigation solution. Rarely, irrigation fluid
may enter the windpipe in people with a poor gag
reflex.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Hypersensitivity Reactions.’’ Section 12, Chapter 148
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Aukema, A. A., and W. J. Fokkens. ‘‘Chronic
Rhinosinusitis: Management for Optimal Outcomes.’’
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Nasal irrigation

Precautions

Resources

Nasal packing

Skull

Sphenoidal sinus

Frontal sinus

Ethmoidal sinus
Cannula
Maxillary sinus

Because surgery in the nasal area has a high incidence rate for contamination with pathogenic bacteria, nasal irrigation is
performed to remove loose tissue and prevent infection. The illustration (right) shows a cannula in place while the sinus
passages are being flushed. (Illustration by Electronic Illustrators Group.)

KEY TERMS

American Academy of Otolaryngology, Head and Neck
Surgery, Inc. One Prince St., Alexandria, VA 223143357. (703) 836-44 44. <http://www.entnet.org>.

Irrigation—In medicine, the practice of washing
out or flushing a wound or body opening with a
stream of water or another liquid.
Saline—A solution made from salt and water.

Treatments in Respiratory Medicine 3 (February 2004):
97–105.
Brown, C. L., and S. M. Graham. ‘‘Nasal Irrigations: Good
or Bad?’’ Current Opinion in Otolaryngology and Head
and Neck Surgery 12 (February 2004): 9–13.
Lavigne, F., M. K. Tulic, J. Gagnon, and Q. Hamid.
‘‘Selective Irrigation of the Sinuses in the Management
of Chronic Rhinosinusitis Refractory to Medical
Therapy: A Promising Start.’’ Journal of
Otolaryngology 33 (February 2004): 10–16.
Paananen, H., M. Holopainen, P. Kalliokoski, et al.
‘‘Evaluation of Exposure to Man-Made Vitreous Fibers
by Nasal Lavage.’’ Journal of Occupational and
Environmental Hygiene 1 (February 2004): 82–87.

Mary K. Fyke
Rebecca J. Frey, PhD

Nasal packing
Definition
Nasal packing is the application of gauze or cotton packs to the nasal chambers.

Purpose
The most common purpose of nasal packing is to
control bleeding following surgery to the septum or
nasal reconstruction and to treat chronic nosebleeds.
Packing is also used to provide support to the septum
after surgery.

ORGANIZATIONS

American Academy of Family Physicians (AAFP). 11400
Tomahawk Creek Parkway, Leawood, KS 66211-2672.
(800) 274-2237 or (913) 906-6000. <http://
www.aafp.org>.
2578

Description
Packing is the placement of gauze or cotton into
the nasal area. Packing comes in three forms: gauze,
GALE ENCYCLOPEDIA OF MEDICINE

In patients who are chronic nose pickers, frequent
bleeding is common and ulceration of nasal tissue is
possible. To promote healing and to prevent nose
picking, both sides of the nose are packed with cotton
that contains antibiotics. The nose is taped shut with
surgical tape to prevent the packing from being
removed. The packing is left in the nose for seven to
10 days. If the wound is high up in the nasal cavity,
gauze strips treated with petrolatum and antibiotics
are used. The strips are placed into the nose one layer
at a time, folding one layer on top of the other until the
area is completely packed.
Local packing is a procedure used when only a
small part of the nose must be packed. Typically, this
occurs when one blood vessel is prone to bleeding, and
there is no need to block breathing through the nose.
Local packing is used when the pack can remain in
place by itself. This situation can be found at the
turbinates. Turbinates are folds of tissue on the insides
of the nose. The folds are sufficiently firm to support
packing. A small piece of gauze or cotton is wedged in
between the turbinates where the blood vessel being
treated is located. Local packing is left in place for up
to 48 hours and then removed. The main advantage to
this type of packing is that it enables the patient to
breathe through his or her nose. Local packing is also
more comfortable than complete packing, although
the patient will still experience a sensation that something is in the nasal cavity. The patient must be
instructed not to interfere with or probe the packing
while it is in place.
A postnasal pack is used to treat bleeding in the
postnasal area. This is a difficult area to pack. Packs
used in this area are made from cotton balls or gauze
that have been tied into a tubular shape with heavy
gauge suture or umbilical tape. Long lengths of suture
or tape are left free. The lengths of suture or tape are
used to help position the pack during installation and
to remove it. An alternative is to cut a vaginal tampon
and reposition the strings. Balloons have been tried as
a method to replace postnasal packing, but have not
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Turbinate—Ridge-shaped cartilage or soft bony tissue inside the nose.
Ulcer—A sore on the skin or mucous tissue that
produces pus and in which tissue is destroyed.

proved effective. After being tied, the pack is soaked
with an antibiotic ointment. Generally, packs are
formed larger than needed, so that they completely
block the nasal passage. A catheter is passed through
the nose and pulled out through the mouth. Strings
from one end of the pack are tied to the catheter and
the pack pulled into place by passing through the
mouth and up the back of the nasal cavity. The pack
is removed in a similar manner. Complications may
occur if a pack compresses the Eustachian tube, causing ear problems. The ear should be examined to
ensure that infection is not developing.
Packing of the anterior (front) part of the nose is
also performed following surgery such as septoplasty
and rhinoplasty. In these operations, the surgeon cuts
through the skin flap covering cartilage and bone in
the center, top, and bottom of the nose to correct the
shape of the nose. At the conclusion of the surgery, the
skin flap is sutured back into place. The purposes of
packing are to absorb any drainage from the incision
and mucus produced by nasal tissue, and to support
the skin flap and cartilage. The packing used is either
gauze or preformed adsorbent wedges of cotton. Both
are usually treated with antibiotic to reduce the chance
of infections at the incision site. Generally, there is
little bleeding following septoplasty and rhinoplasty,
and the incisions heal normally. These packs are left in
place for 24 to 48 hours and then removed.

Aftercare
Ice chips or mouthwash can be used to moisten the
mouth while packing is in place, as the mouth may be
dry from breathing through it. Humidifiers may also
help with breathing. After nasal packing, the nose
should not be blown for two to three days.
Since one of the major reasons that packing is
performed is to heal damage to nasal blood vessels
from nose-picking, follow-up examination should be
done to ensure that the patient is no longer practicing
this habit. If the patient has restarted nose-picking,
therapy to alter this behavior should be pursued.
When the packing completely blocks the nasal cavity
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Nasal packing

cotton balls, and preformed cotton wedges. Packing
is usually coated with antibiotics and, sometimes,
petrolatum. The end of the nose may be taped to
keep the packings in place or to prevent the patient
from pulling them out. In cases of surgery, packings
are frequently removed within 24–48 hours following
surgery. In the case of nosebleeds, packing is left in for
extended periods of time to promote healing and to
prevent the patient from removing scar tissue which
might reopen the wound. If both sides of the nose are
packed, the patient must breathe through his or her
mouth while the packs are in place.

Nasal polyps

and prevents breathing through the nose, the patient
should adjust to breathing through the mouth. In
elderly patients, adjustment may be more difficult.
This leads to a drop in the blood oxygen content and
an increase in blood carbon dioxide levels (CO2). This,
in turn, can cause respiratory and cardiac complications, including a racing pulse.

KEY TERMS
Polyp—A tumor commonly found in the nasal cavity or intestine.

Diagnosis

Risks
Nasal packing could cause a lack of oxygen in
those who have difficulty breathing through their
mouths. Rarely, sinus infection or middle ear infection
may occur.
Resources
BOOKS

Bluestone, C. D., S. E. Stool, and M. A. Kenna.
Pediatric Otolaryngology. Philadelphia: W. B. Saunders
Co., 1996.

John T. Lohr, PhD

A physical examination with special instruments
will detect these tumors.

Treatment
Because of the possibility of cancer, all nasal
papillomas must be removed surgically and sent to
the laboratory for analysis. If a cancer is present,
further surgery may be necessary to guarantee that
all of the cancer has been removed. The initial surgery
can be done in an office setting by a specialist in head
and neck surgery, also known as otorhinolaryngology
and popularly abbreviated ENT (ear, nose, and
throat). Cancer surgery is more extensive and often
requires hospitalization.

Prognosis

Nasal papillomas
Definition
Nasal papillomas are warts located inside the nose.

Description
Two types of tumors can grow inside the nose:
polyps and papillomas. By far the most common are
polyps, which have smooth surfaces. On the contrary,
papillomas have irregular surfaces and are, in fact,
warts. Papillomas may be caused by the same viruses
that cause warts elsewhere on the body. They are
inside the nose, more often on the side near the
cheek, and, because of their internal structure, they
are much more likely to bleed than polyps.
There is a special type of nasal papilloma called
an inverting papilloma because of its unique appearance. About 10 or 15% of these are or can become
cancers.

Causes and symptoms
Like polyps, papillomas can plug up the nose and
disable the sense of smell. Unlike polyps, papillomas
often bleed.
2580

For benign (non-cancerous) lesions, removal is
curative, although they tend to recur, just like warts
elsewhere. The cancerous papillomas may occasionally escape complete surgical removal and spread to
adjacent or distant sites. The prognosis is then much
more complex.
Resources
BOOKS

Ballenger, John Jacob. Disorders of the Nose, Throat, Ear,
Head, and Neck. Philadelphia: Lea & Febiger,1996.

J. Ricker Polsdorfer, MD

Nasal polyps
Definition
A polyp is the medical term for any overgrowth of
tissue from the surface of a body organ. Polyps come
in all shapes—round, droplet, and irregular being the
most common. Nasal polyps are teardrop-shaped
while growing and resemble peeled grapes when they
GALE ENCYCLOPEDIA OF MEDICINE

Nasal polyps

have reached their full size. The condition of nasal
polyps is sometimes called nasal polyposis.

Description
Nasal polyps tend to occur in people with respiratory allergies. Hay fever (allergic rhinitis) is an irritation of the membranes of the nose by airborne
particles or chemicals. These membranes secrete
mucus. When irritated, they can also grow polyps.
The nose is not only a passageway for air to reach
the lungs; it also provides the connection between the
sinuses and the outside world. Sinuses are lined with
mucous membranes, just like the nose. Polyps can
easily obstruct the drainage of mucus from the sinuses.
When any fluid in the body is trapped so it cannot flow
freely, it becomes infected. The result, sinusitis, is a
common complication of allergic rhinitis.

A nasal polyp inside patient’s right nostril. (Custom Medical
Stock Photo. Reproduced by permission.)

Nasal polyps may also develop in children with
cystic fibrosis.

Causes and symptoms
Some people who are allergic to aspirin develop
both asthma and nasal polyps.
Nasal polyps often plug the nose, usually one
side at a time. People with allergic rhinitis are so
used to having a stopped-up nose they may not notice
the difference when a polyp develops. Other polyps
may be closer to a sinus opening, so airflow is not
obstructed, but mucus becomes trapped in the sinus.
In this case, there is a feeling of fullness in the
head, no sense of smell, and perhaps a headache.
The trapped mucus will eventually get infected, adding pain, fever, and perhaps bloody discharge from
the nose.

KEY TERMS
Allergen—Any substance that irritates only those
who are sensitive (allergic) to it.
Asthma—Wheezing (labored breathing) due to
allergies or irritation of the lungs.
Decongestant—Medicines that shrink blood
vessels and consequently mucus membranes.
Pseudoephedrine, phenylephrine, and phenylpropanolamine are the most common.
Polyposis—The medical term for the development
of multiple polyps on a body part.
Sinus—Air-filled cavities surrounding the eyes
and nose are lined with mucus-producing membranes. They cleanse the nose, add resonance to
the voice, and partially determine the structure of
the face.

Diagnosis
A physical examination will identify most polyps.
Small polyps located higher up or further back may be
hidden from view, but they will be detected with more
sophisticated medical instruments. The otorhinolaryngologist is equipped to diagnose nasal polyps. In
order to perform the examination, the doctor must
apply medicine to reduce congestion in the swollen
membranes. Cotton balls soaked with one of these
agents and left in the nostrils for a few minutes provide
adequate shrinkage.

Treatment
Most polyps can be removed by the head and neck
surgeon as an office procedure called a nasal
GALE ENCYCLOPEDIA OF MEDICINE

polypectomy. Bleeding, the only complication, is
usually easy to control. Nose and sinus infections can
be treated with antibiotics and decongestants, but if
airflow is restricted, the infection will recur.

Prognosis
Polyps may reappear as long as the allergic
irritation continues. In addition, one study of
patients who had undergone nasal polypectomy
reported that 60% had a recurrence of nasal polyposis, and 47% were advised to have revision surgery.
The risk of recurrence is higher among patients with
asthma.
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Nasal trauma

Prevention
If aspirin is the cause of the polyps, all aspirin
containing medications must be avoided.
Since most nasal polyps are the result of allergic rhinitis, they can be prevented by treating this
condition. New treatments have greatly improved
control of hay fever. There are now several spray
medicines that are quite effective. Spray cortisonelike drugs, usually beclomethasone (Beconase,
Vancenase) or flunisolide (Nasalide), are the most
popular. Over-the-counter nasal decongestants have
an irritating effect similar to the allergy they are
supposed to be treating. Continued use can bring
more trouble than relief and result in an addiction
to nose sprays. The resulting disease, rhinitis medicamentosa, is more difficult to treat than allergic
rhinitis.
Allergists and ENT surgeons both treat allergic
rhinitis with a procedure called desensitization. After
identifying suspect allergens using one of several methods, they will give the patient increasing doses of those
allergens in order to produce blocking antibodies that
will impede the allergic reaction. This approach is
effective in a number of patients, but the treatment
may take a period of months to years.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Nose and Paranasal Sinuses: Polyps.’’ Section 7,
Chapter 86 In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Bikhazi, N. B. ‘‘Contemporary Management of Nasal
Polyps.’’ Otolaryngologic Clinics of North America 37
(April 2004): 327–337.
Drake-Lee, A. B. ‘‘Nasal Polyps.’’ Hospital Medicine 65
(May 2004): 264–267.
Wynn, R., and G. Har-El. ‘‘Recurrence Rates after
Endoscopic Sinus Surgery for Massive Sinus
Polyposis.’’ Laryngoscope 114 (May 2004): 811–813.
ORGANIZATIONS

American Academy of Allergy, Asthma and Immunology
(AAAAI). 611 East Wells Street, Milwaukee, WI 53202.
(800) 822-2762. <http://www.aaaai.org>.
American Academy of Otolaryngology–Head and Neck
Surgery, Inc. One Prince Street, Alexandria, VA 223143357. (703) 836-4444. <http://entnet.org>.

J. Ricker Polsdorfer, MD
Rebecca J. Frey, PhD
2582

Nasal trauma
Definition
Nasal trauma is defined as any injury to the nose
or related structure that may result in bleeding, a
physical deformity, a decreased ability to breathe normally because of obstruction, or an impaired sense of
smell. The injury may be either internal or external.

Description
The human nose is composed of bone, soft tissue,
and cartilage. It serves as a passageway for air to flow
from the outside environment into the lower respiratory tract and lungs. At the same time, the nasal passages warm and humidify the air that enters the body.
Internal injuries to the nose typically occur when a
foreign object (including the fingers) is placed in the
nose or when a person takes in drugs of abuse (inhalants
or cocaine) through the nose. External injuries to the
nose are usually blunt force injuries related to sports
participation, criminal violence, parental abuse, or
automobile or bicycle accidents. This type of injury
may result in a nasal fracture. The nasal bones are the
most frequently fractured facial bones due to their
position on the face, and are the third most common
type of bone fracture in general after fractures of the
wrist and collarbone. A force of only 30g is required to
break the nasal bones, compared to 70g for the bones in
the jaw and 200 g for the bony ridge above the eyes. The
pattern of the fracture depends on the direction of
the blow to the nose, whether coming from the
front, the side, or above the nose. Although not lifethreatening by itself, a fractured nose may lead to difficulties in breathing as well as facial disfigurement.
Fractures resulting from trauma to the nose may
involve the bones of the septum (the partition of bone
and cartilage dividing the two nostrils) as well as the
bones surrounding the eyes. These bones include the
nasal, maxilla, lacrimal, and frontal bones. Direct
trauma to the bridge of the nose may also result in
damage to a part of the base of the skull known as the
cribriform plate. This injury in turn may allow cerebrospinal fluid to leak out of the skull and leave the
body through the nose. Fractures may also damage
the membranes that line the nasal passages, leading to
possible formation of scar tissue, obstruction of the
airway, and damage to the child’s sense of smell.
In addition to fractures, external injuries of the nose
include soft-tissue injuries resulting from bites (human
and animal), insect stings, cuts, or scrapes. Penetrating
injuries to the nasal area caused by air gun or BB pellets
GALE ENCYCLOPEDIA OF MEDICINE

Fractured nose of an elderly patient. (Photograph by Dr.
P Marazzi. Photo Researchers. Reproduced by permission.)

are also reported with increasing frequency in older
children and adolescents. When fired at close range,
these pellets can penetrate the skin and cheekbone and
lodge in the nasal septum or the sinuses near the nose.
Lastly, nose piercing as a fashion trend is a type of
intentional injury to the nose that has several possible
complications, including infections of the cartilage
and soft tissues in the nose; blockage of the airway
due to a loosened stud or other nose ornament; and
gastrointestinal emergencies caused by accidental
swallowing of nose jewelry.

Causes and symptoms

Chemical injuries to the nose are caused by accidental or purposeful breathing or sniffing of irritating
substances. These may include tobacco smoke; household cleaners (ammonia and chlorine bleach) and
furniture polish; ozone and other air pollutants;
cocaine; and glue, paint thinners, solvents, and similar
household products that produce toxic vapors. An
increasingly common form of chemical injury to the
nasal membranes in toddlers is alkali burns caused by
leakage from small batteries placed in the nose. While
chemical damage to the nose is usually accidental in
younger children, it is more often the result of substance abuse in adolescents. Taking cocaine through
the nose (‘‘snorting’’) or inhalant abuse (‘‘sniffing’’ or
‘‘huffing’’) are the most common causes of chemical
damage to the nose in older children or teenagers.
Symptoms
The symptoms of physical trauma to the nose may
include:


Flattening or other deformation of the shape of the
nose



Infections of the cartilage or soft tissue



Epistaxis or bleeding from the nose



Crepitus. Crepitus is the crackling or crunching
sound heard when the ends of a fractured bone are
rubbed together



Pain and tissue swelling



Airway blockage from bleeding, fluid discharge, or
tissue swelling



Rhinitis. Rhinitis is an inflammation of the mucous
membranes lining the nose. In the case of a fracture,
rhinitis may lead to increased tear production in the
eyes and a runny nose



Septal hematoma. A septal hematoma is a mass of
blood from torn tissue that may collect within the
cartilage that divides the two nostrils. It may become
infected and form an abscess that eventually destroys
the cartilage



Bruising or discoloration (ecchymosis) of the tissues
around the eye



Leakage of cerebrospinal fluid through the nostrils

Causes
External trauma to the nose may be accidental
(transportation accidents, animal bites, air gun injuries, and sports injuries) or intentional (fights, criminal
assault, domestic violence, nose piercing). Nasal injuries from athletic activities may result from contact
with equipment (being hit in the face by a baseball,
hockey ball, or other small ball hit at high speed, or by
the bat or stick itself) or the bodies of other players
(football, boxing, martial arts, rugby). Nasal injuries
from piercing include bacterial infections of the skin
and nasal cartilage, allergic reactions to the jewelry,
tissue damage, and periodic bleeding.
In a few cases, external trauma to the nose may
also be iatrogenic, or caused by medical care. Most of
these injuries result from medical examination of the
nose—particularly in emergency circumstances—or as
complications of plastic surgery. In a few cases damage
to the nose is caused by radiation therapy for cancer.
Internal injuries to the nose may be either
mechanical (caused by foreign objects in the nose or
GALE ENCYCLOPEDIA OF MEDICINE

Chemical trauma to the nose may result in:


Runny nose and watering of the eyes



Pain
2583

Nasal trauma

by picking or scratching the tissues lining the nose) or
chemical (caused by environmental irritants or substance abuse).

Nasal trauma



Loss of the sense of smell



Nasal congestion and sneezing



Reddening and swelling of the mucous membranes
lining the nose



Eventual destruction of the cartilage in the nasal
septum and the tissues lining the nose

Some common irritants that may be encountered
in the home and workplace include:


cleaning solutions and powders



ammonia



environmental tobacco smoke



bleach



metalworking fluids



ozone



sulfur dioxide



paint thinners



arsenic



chromic acid



copper dust and mists

Sequelae following exposure to these chemicals
are based not only on the concentration of the irritant
but also on factors specific to the individual. Reactions
vary among persons, even with similar exposures.

Diagnosis
Diagnosis of a fracture is normally based on a history of nasal trauma and clinical presentation. Epistaxis
may or may not be present. An intranasal examination
is performed in order to look for a septal hematoma that
may result in serious consequences such as death of
the septal cartilaginous tissue. The nose is also checked
for tenderness, mobility, stability, and crepitance.
X rays are normally not indicated, however, in
more severe fractures involving multiple bones, a computed tomography (CT) scan may be required. The
physician should look for associated injuries such as
periorbital (surrounding the eye) ecchymosis, watery
eyes, or diplopia (double vision) that may indicate
orbital injuries. In addition, dental fractures and a
cerebrospinal fluid (CSF) leak should be looked for.
CSF leaks indicate a more severe injury possibly involving an ethmoid bone fracture.
The physician may also ask for photographs taken
prior to the injury in order to determine the extent of
deformity. Photographs may also be taken to document the injury in regards to possible legal actions.
2584

In order to diagnose trauma sustained by a chemical injury, a history of exposure to potentially toxic
chemicals should be ascertained. In addition, the
patient should also bring information related to the
types of chemicals that he or she has been exposed to.
If injury occurs in the workplace, Material Safety
Data Sheets should be available in the employer’s
poison control center that list the chemical components of commercial materials. Measurements of air
from the patient’s work area may also be obtained.
Symptomatic improvement on off-days followed by a
subsequent return of symptoms when returning to
work confirms that the illness is work related. The
physician should perform an intranasal examination
to determine the extent of the chemical injury. A chest
x ray as well as a pulmonary function test may be
ordered to determine if there is any subsequent lower
respiratory tract involvement.

Treatment
Timing
Nasal injuries should be treated as promptly as
possible to prevent complications. Batteries placed in
the nose should be removed within 4 hours to prevent
burns and other damage to the tissues from leaking
chemicals. If a septal hematoma has developed, the
doctor must remove it as quickly as possible to prevent
infection or eventual death of the tissues in the nasal
septum. Lastly, if the child has been bitten by an
animal, the injury must be cleansed as soon as possible
to lower the risk of rabies.
Treatment of nasal fractures is best performed
during the first three hours after the injury. If this is
impossible, management of a nasal fracture should be
done within three to seven days. Timing is of utmost
importance when treating nasal fractures because
delays longer than seven to 10 days may allow the
broken bones to set without proper alignment, or
lead to such complications as scar tissue formation
and airway obstruction. Poorly set nasal fractures
usually require surgical correction.
Specific procedures
Foreign objects in the nose can be removed by
nasal suction in most cases. Most nosebleeds are treated by 5–30 minutes of direct pressure on the nostrils,
with the patient’s head placed in an upright position.
The doctor may also pack the nose with gauze coated
with petroleum jelly. If the bleeding does not stop, or if
it appears to originate in the upper nose, the doctor
will consult a head and neck surgeon or an otolaryngologist for specialized evaluation of the bleeding.
GALE ENCYCLOPEDIA OF MEDICINE

contaminated area or decreasing exposure time.
Other measures include using a saline nasal spray or
topical steroids. For acute injuries oxygen or supportive treatment for any subsequent lower respiratory
tract involvement may be administered.

Treatment of nasal fractures depends on the extent
of the injury; the most difficult fractures to treat are
those that involve the nasal septum. The doctor will
usually reduce the fracture, which means that he or she
will restore the damaged bones to their proper position
and alignment. Although local anesthesia is usually
sufficient for treating nasal fractures in adults and
older teenagers, general anesthesia is usually given
when treating these injuries in younger children.

If the injury is occupation-related, changes should
be made in order to eliminate future incidents. These
changes may include having the patient wear
a respiratory protection device while working. In addition, the employer should be made aware of the situation and employ measures to prevent future incidents.

Reductions of nasal fractures may be either open
or closed. A closed reduction involves manipulation of
the bones without cutting into the overlying skin. This
type of reduction will be performed for fractures of the
nasal bones that are limited in size and complexity.
Open reductions are performed for more complex
nasal fractures. In an open reduction, the nasal bones
are moved back to their original location after the
surgeon has made an incision in the overlying skin.
This procedure is done for fractures involving dislocation of the septum as well as the nasal bones. In addition, an open reduction is necessary if the child has a
septal hematoma or an open fracture in which the skin
has been perforated. If a septal hematoma is present,
the doctor will drain it and pack the nose to prevent
subsequent accumulation of blood. The nasal bones
are held in the proper position with external splints as
well as the internal packing, and the splints are kept in
place for 7–10 days. The patient will be given antibiotics to lower the risk of infection and may be referred
to an otolaryngologist or plastic surgeon for further
evaluation. Ice packs or cold compresses can be
applied at home to lower swelling and ease discomfort.
In the case of animal bites, the patient may be given
passive or active immunization against rabies if there is
a chance that the dog or other animal is rabid. This
precaution is particularly important for animal bites on
the nose or other parts of the face, as the incubation
period of the rabies virus is much shorter for bites on
the head and neck than for bites elsewhere on the body.
Complications can arise following treatment and
therefore follow-up is necessary. Problems that may
occur resemble symptoms of nasal fractures. Others
include infection, CSF leakage, scar tissue build-up,
and a saddle nose deformity where the bridge of the
nose is markedly depressed.
Treatment for trauma caused by irritant inhalation involves removing the patient from the
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Most types of nasal trauma have a good prognosis. Nosebleeds or tissue damage caused by scratching or picking at the nose usually clear completely once
these habits are stopped. Infections or allergic reactions caused by foreign objects in the nose or piercing
usually clear up promptly after the object or piece of
jewelry is removed. Nasal fractures that do not involve
the nasal septum or other facial bones and receive
prompt treatment generally heal without deformities
of the nose, cartilage destruction, or other complications. More extensive facial fractures, however, may
require a second operation to correct the positioning
of the bones and restore the appearance of the nose.
The prognosis for soft-tissue injuries to the nose
depends on the cause and extent of the injuries. Such
tearing or crushing injuries as those caused by bites
take longer to heal than simple cuts, and may require
plastic surgery at a later date to restore the appearance
of the nose.
Damage to the tissues lining the nose caused by
exposure to tobacco smoke or other irritants in the
environment is usually reversible once the patient is
removed from contact with the irritating substance.
Erosion or destruction of the nasal cartilage as a result
of inhalant or cocaine abuse, however, usually
requires surgical treatment.

Prevention
Although most cases of nasal trauma happen
inadvertently, some measures can be employed in
order to prevent injury. Patients should be aware
of the symptoms of nasal fracture and should seek
medical attention as soon as possible to prevent more
invasive reductions. Protective equipment should also
be worn when playing sports. Employees should also
be aware of irritating chemicals in their workplace and
appropriate measures should be taken to avoid
exposure.
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Nasal trauma

Air gun or BB pellets that have penetrated the
nose or nearby sinuses are generally removed with
the help of an endoscope, which is a slender tubular
instrument that allows the doctor to examine the
inside of a body cavity.

Nasogastric suction

KEY TERMS
Crepitus—A crackling or crunching sound heard
when the ends of a fractured piece of bone rub
against each other.
Diplopia—The medical term for seeing double.
Ecchymosis (plural, ecchymoses)—The medical
term for a bruise. Ecchymoses may develop around
the eyes following a nasal fracture.
Epistaxis—The medical term for a nosebleed.
Hematoma—A localized collection of blood that
accumulates in an organ, tissue, or body space as
the result of leakage from a broken blood vessel.
Hematomas sometimes develop within the nasal
cartilage when the nose is fractured.
Iatrogenic—Referring to injuries caused by a doctor. Nasal trauma may occasionally result from a
doctor’s examination of the nose or complications
from plastic surgery.
Otolaryngologist—A doctor who specializes in
diagnosing and treating disorders of the ears,
nose, and throat.
Reduce—To restore a part of the body to its normal
position or place, as in treating a fracture or dislocation. The repositioning of the bone or body part is
called a reduction.
Rhinitis—An inflammation of the mucous membranes that line the nasal passages.
Rhinoplasty—Plastic surgery of the nose to repair
or change the shape of the nose.
Septal hematoma—A mass of extravasated blood
that is confined within the nasal septum.
Septum—The partition of bone and cartilage in the
nose that separates the two nostrils.

Anderson, Carrie E., MD, and Glenn A. Loomis, MD.
‘‘Recognition and Prevention of Inhalant Abuse.’’
American Family Physician 68 (September 1, 2003):
869–876.
Brinson, G. M., B. A. Senior, and W. G. Yarbrough.
‘‘Endoscopic Management of Retained Airgun
Projectiles in the Paranasal Sinuses.’’ Otolaryngology
and Head and Neck Surgery 130
(January 2004): 25–30.
Kalavrezos, N. ‘‘Current Trends in the Management of
Frontal Sinus Fractures.’’ Injury 35 (April 2004):
340–346.
Mahajan, M., and N. Shah. ‘‘Accidental Lodgment of an
Air Gun Pellet in the Maxillary Sinus of a 6-Year-Old
Girl: A Case Report.’’ Dental Traumatology 20 (June
2004): 178–180.
Ross, Adam T., MD, and Daniel G. Becker, MD.
‘‘Fractures, Nasal and Septal.’’ eMedicine July 13, 2004.
<http://www.emedicine.com/ent/topic159.htm>.
Rupp, Timothy J., MD, Marian Bednar, MD, and Stephen
Karageanes, DO. ‘‘Facial Fractures.’’ eMedicine
August 29, 2004. <http://www.emedicine.com/sports/
topic33.htm>.
Tu, A. H., J. A. Girotto, N. Singh, et al. ‘‘Facial Fractures
from Dog Bite Injuries.’’ Plastic and Reconstructive
Surgery 109 (April 1, 2002): 1259–1265.
ORGANIZATIONS

American Academy of Family Physicians (AAFP). 11400
Tomahawk Creek Parkway, Leawood, KS 66211-2672.
(800) 274-2237 or (913) 906-6000.<http://
www.aafp.org>.
American Academy of Otolaryngology—Head and Neck
Surgery. One Prince Street, Alexandria, VA 22314-3357.
(703) 836-4444. <http://www.entnet.org>.
American College of Sports Medicine (ACSM). 401 West
Michigan Street, Indianapolis, IN 46202-3233.
(317) 637-9200. Fax: (317) 634-7817.
<http://www.acsm.org>.

Laith Farid Gulli, M.D.
Robert Ramirez, B.S.
Rebecca J. Frey, PhD

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Fractures of the Nose.’’ Section 7, Chapter 86 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Jackler, Robert K., and Michael J. Kaplan. ‘‘Ear, Nose, and
Throat.’’ In Current Medical Diagnosis and Treatment,
edited by Lawrence M. Tierney, Jr., et al. New York:
Lange Medical Books/McGraw-Hill, 2001.
PERIODICALS

Alvi, A., T. Doherty, and G. Lewen. ‘‘Facial Fractures
and Concomitant Injuries in Trauma
Patients.’’ Laryngoscope 113 (January 2003): 102–106.
2586

Nasogastric suction
Definition
Nasogastric suction involves removing solids,
liquids, or gasses from the stomach or small intestine
by inserting a tube through the nose and suctioning the
gastrointestinal material through the tube.
GALE ENCYCLOPEDIA OF MEDICINE

Nasogastric suction may be done in the following
situations:


to decompress the stomach or small intestine when
intestinal obstruction (ileus) is suspected



prior to gastrointestinal operations



to obtain a sample of the gastric contents for analysis



to remove toxic substances



to flush the stomach during gastrointestinal bleeding
or poisonings

Nasogastric intubation, the insertion of a tube
through the nose into the stomach or small intestine,
is also done to temporarily feed certain patients. In
this case, material is not suctioned out.

Precautions
Nasogastric tubes cannot be placed in patients
who have blockages in their esophagus, enlarged esophageal veins or arteries that might bleed, or severe
damage to the jaws and face. The tube cannot be
inserted in a patient who is having convulsions, or
who is losing or has lost consciousness unless a tube
has been inserted into his or her airway (intubation).

Description
The patient sits upright while a lubricated tube is
slipped through the nose and down the throat. The
patient may be asked to sip water at a certain point in
the procedure to facilitate the passage of the tube. If the
tube is to be placed into the small intestine, the doctor
may use an endoscope to help see where the tube is
going. Once the tube is in place, material can be removed
from the stomach or intestines with gentle suction.
There are several different types of nasogastric
tubes, each with a different purpose. Tubes used for
stomach flushing are called orogastric tubes and are the
largest in diameter. Tubes that are threaded through
the lower opening of the stomach (pylorus) and into
the small intestine are stiffer and have a balloon tip.
Other specialized tubes are used for long-term and
short-term feeding.

Preparation
Little preparation is necessary for this procedure
other than educating the patient as to what will happen. The patient should remove dental appliances
before the nasogastric tube is inserted.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Endoscope—A piece of equipment with a camera
and a light source in a thin tube that can be
threaded through the nose into the gastrointestinal
system so that the doctor can make a real-time
visual examination.
Pylorus—The ring of muscle that controls the passage of material from the stomach into the small
intestine.

Aftercare
After the tube is removed, no special care is
needed. The patient’s throat may feel irritated from
the presence of the tube.

Risks
The most serious risk is that the patient will inhale
some of the stomach contents into the lungs (aspiration). This may lead to bronchial infections and
aspiration pneumonia. There is also the chance that
the tube will be misplaced in the windpipe (trachea),
causing violent coughing. Irritation to the throat and
esophagus can cause bleeding.

Normal results
Nasogastric suctioning is normally well tolerated
by patients and is a temporary treatment, performed
in conjunction with other therapies.
Resources
BOOKS

Berkow, Robert, editor. ‘‘Nasogastric or Intestinal
Intubation.’’ In The Merck Manual of Diagnosis
and Therapy. Rahway, NJ: Merck Research
Laboratories, 2004.

Tish Davidson, A.M.

Nasopharyngeal culture
Definition
A nasopharyngeal culture is used to identify pathogenic (disease-causing) organisms present in the nasal
cavity that may cause upper respiratory tract symptoms.
2587

Nasopharyngeal culture

Purpose

Nasopharyngeal culture

Purpose
Some organisms that cause upper respiratory
infections are carried primarily in the nasopharynx,
or back of the nose. The person carrying these pathogenic bacteria may have no symptoms, but can still
infect others with the pathogen and resulting illness.
The most serious of these organisms is Neisseriea
meningitidis, which causes meningitis or blood stream
infection in infants. By culturing a sample from the
nasopharynx, the physician can identify this organism,
and others, in the asymptomatic carrier. The procedure can also be used as a substitute for a throat culture
in infants, the elderly patient, the debilitated patient,
or in cases where a throat culture is difficult to obtain.

Precautions

species of pneumococci and other organisms that
cause pneumonia. The immunoblot method uses a
membrane that changes color in response to a specific
antigen-antibody reaction.
As of the early 2000s, polymerase chain reaction
(PCR) analysis is considered more sensitive than
standard culture in detecting Bordetella pertussis, the
bacterium that causes whooping cough. PCR has the
additional advantage of providing test results more
rapidly than culture.

Preparation
The procedure of inserting the swab should be
described to the patient, as there is a slight discomfort
associated with taking the sample. Other than that, no
special preparation is necessary.

The technician taking the specimen should wear
gloves to prevent spreading infectious organisms. The
patient should not be taking antibiotics, as these drugs
may influence the test results.

Aftercare
None

Risks
Description
The patient should cough before collection of the
specimen. Then, as the patient tilts his or her head
backwards, the caregiver will inspect the back of the
throat using a penlight and tongue depressor. A swab
on a flexible wire is inserted into the nostril, back to
the nasal cavity and upper part of the throat. The swab
is rotated quickly and then removed. Next, the swab is
placed into a sterile tube with culture fluid in it for
transport to the microbiology laboratory. To prevent
contamination, the swab should not touch the
patient’s tongue or side of the nostrils.
When the sample reaches the laboratory, the swab
will be spread onto an agar plate and the agar plate
incubated for 24–48 hours, to allow organisms present
to grow. These organisms will be identified and any
pathogenic organisms may also be tested for susceptibility to specific antibiotics. This allows the treating physician to determine which antibiotics will be effective.
Alternative procedures
In most cases of upper respiratory tract infections,
a throat culture is more appropriate than a nasopharyngeal culture. However, the nasopharyngeal culture
should be used in cases where throat cultures are difficult to obtain or to detect the carrier states of
Harmophilus influenzae and meningococcal disease.
Some researchers regard the immunoblot method
as preferable to a standard culture to detect certain
2588

There is little to no risk involved in a nasopharyngeal culture.

Normal results
Bacteria that normally grow in the nose cavity will
be identified by a nasopharyngeal culture. These
include nonhemolytic streptococci, alpha-hemolytic
streptococci, some Neisseria species, and some types
of staphylococci.

Abnormal results
Pathogenic organisms that might be identified by
this culture include


Group A beta-hemolytic streptococci



Bordetella pertussis, the causative agent of whooping
cough



Corynebacterium diptheriae, the causative agent of
diptheria



Staphylococcus aureus, the causative agent of many
staphylococcal infections.

Additional bacteria are abnormal if they are
found in large amounts. These include


Haemophilus influenzae, a causative agent for certain
types of meningitis and chronic pulmonary disease.



Streptococcus pneumoniae, a causative agent of
pneumonia



Candida albicans, the causative agent of thrush.
GALE ENCYCLOPEDIA OF MEDICINE

Antibiotic—A drug given to stop the growth of
bacteria. Antibiotics are ineffective against viruses.
Nasopharynx—The back wall of the nasal cavity
where it meets the throat.

medicine are diet, nutrition, homeopathy, physical
manipulation, stress management, and exercise.
Naturopaths are general practitioners who treat a
wide variety of illnesses. They believe in treating the
‘‘whole person’’—the spirit as well as the physical
body—and emphasize preventive care. They often
recommend changes in diet and lifestyle to enhance
the health of their patients.

Purpose

Resources
BOOKS

Byrne, J., D. F. Saxton, P. K. Pelikan, and P. M. Nugent.
Laboratory Tests, Implication for Nursing Care. 2nd ed.
Menlo Park, CA: Addison-Wesley Publishing Company.
PERIODICALS

Bronsdon, M. A., K. L. O’Brien, R. R. Facklam, et al.
‘‘Immunoblot Method to Detect Streptococcus
pneumoniae and Identify Multiple Serotypes from
Nasopharyngeal Secretions.’’ Journal of Clinical
Microbiology 42 (April 2004): 1596–1600.
Fry, N. K., O. Tzivra, Y. T. Li, et al. ‘‘Laboratory Diagnosis
of Pertussis Infections: The Role of PCR and
Serology.’’ Journal of Medical Microbiology 53 (June
2004): 519–525.

Naturopathic medicine is useful for treating
chronic as well as acute diseases. It is sometimes used
in conjunction with allopathic care to enhance wellness and relieve chronic symptoms, such as fatigue
and pain. A naturopath treats a wide range of health
problems, ranging from back pain to depression.
A naturopathic physician will spend extra time
interviewing and examining the patient to find the
underlying cause for a medical problem. Emotional
and spiritual symptoms and patterns are included in
the assessment. The naturopath often spends more
time educating patients in preventive health, lifestyle,
and nutrition than most M.D.s.

ORGANIZATIONS

American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://
www.ama-assn.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Cindy L. A. Jones, PhD
Rebecca J. Frey, PhD

Native American health see Minority health

Naturopathic medicine
Definition
Naturopathic medicine is a branch of medicine in
which a variety of natural medicines and treatments
are used to heal illness. It uses a system of medical
diagnosis and therapeutics based on the patterns of
chaos and organization in nature. It is founded on
the premise that people are naturally healthy, and
that healing can occur through removing obstacles
to a cure and by stimulating the body’s natural healing abilities. The foundations of health in natural
GALE ENCYCLOPEDIA OF MEDICINE

Description
Origins
People have always seen a connection to diet and
disease, and many therapies are built around special
diets. Naturopathy began in the eighteenth and nineteenth centuries, as the industrial revolution brought
about unhealthy lifestyles, and the European custom of
‘‘taking the cure’’ at natural spas became popular.
Benedict Lust, who believed deeply in natural medicine,
organized naturopathy as a formal system of healthcare
in the 1890s. By the early 1900s, it was flourishing.
The first naturopaths in the United States emphasized the healing properties of a nutritious diet, as did
a number of their contemporaries. In the early twentieth century, for instance, John Kellogg, a physician
and vegetarian, opened a sanitarium that used healing
methods such as hydrotherapy, often prescribed by
today’s naturopaths. His brother Will produced
health foods, such as corn flakes and shredded
wheat. The Post brothers helped make naturopathic
ideas popular and emphasized the value of whole
grains over highly refined ones. Together with one of
their employees, C.W. Post, they eventually went on to
start the cereal companies that bear their names.
In the early 1900s, most states licensed naturopaths as physicians. There were 20 medical schools of
2589

Naturopathic medicine

KEY TERMS

Naturopathic medicine

naturopathic medicine. From early on, naturopathic
physicians were considered ‘‘eclectic,’’ since they drew
on a variety of natural therapies and traditions for
treating their patients.

In some states, naturopaths prescribe pharmaceuticals. In these cases, naturopaths might prescribe natural medicines, such as natural hormones, glandular
thyroid hormones, herbal extracts, vitamins, etc.

In the 1930s, naturopathy dramatically declined
for several reasons. Allopathic medicine finally
stopped using therapies such as bloodletting and
heavy metal poisoning as curatives. New therapies
were more effective and less toxic. Allopathic
medical schools became increasingly well-funded by
foundations with links to the emerging drug industry.
Also, allopathic physicians became much more organized and wielded political clout. Naturopathy has
experienced a resurgence over the last 20 years, however. The lay public is aware of the connection
between a healthy diet and lifestyle and avoiding
chronic disease. In addition, conventional medicine is
often unable to treat these chronic diseases. Patients
are now health care consumers, and will seek their own
resolution to health problems that cannot be resolved
by conventional physicians. As a result, even medical
groups which once considered naturopathy ineffective
are now beginning to accept it.

As with most doctors, treatment by a naturopath
can range from one office visit to many. Some acute
illnesses can be alleviated with one or two visits. Other
chronic diseases need regular weekly or monthly attention. Clinical care provided by naturopathic physicians are covered by insurance in a number of states
in the United States.

Naturopathic medicine modalities include a variety of healing treatments, such as diet and clinical
nutrition, homeopathy, botanical medicine, soft tissue
and spinal manipulation, ultrasound, and therapeutic
exercise. A naturopath provides complete diagnostic
and treatment services in sciences such as obstetrics,
pediatrics and obstetrics. Some are also licensed
midwives.
Naturopaths consider health to be not just the
absence of disease, but complete physical, mental
and social well being. Naturopathic physicians often
say that diseases must be healed not just by suppressing symptoms, but by rooting out the true cause.
Symptoms are actually viewed as the body’s natural
efforts to heal itself and restore balance.
A typical office visit to a naturopath takes an
hour. During the first visit, the doctor will ask
detailed questions about the patient’s symptoms,
lifestyle, history of illness, and state of his or her
emotions. The naturopath will take a complete medical history, and may order lab tests such as urine and
blood tests. A naturopath may talk with the patient
about the possible causes for an illness—poor diet,
life stresses, occupational dangers, and mental,
emotional, and spiritual problems. Naturopaths
believe that even widely varying symptoms can
sometimes be traced to one underlying cause. Often
environmental or metabolic toxins or serious stress
bring on an illness.
2590

Preparations
There were about 1,500 naturopathic physicians in
the United States practicing as of 2004; nearly 80% of
these practitioners entered the profession following
the revival of interest in naturopathy in the late
1970s. Consumers can find naturopaths by contacting
the American Association of Naturopathic Physicians
(AANP) or logging on to their web site. Naturopaths
recommended by the AANP have met requirements
for state licensure and have taken a national exam that
qualifies them to practice. Qualified naturopaths can
also be found through the local branch of the national
or state association of naturopathic physicians. It is
sometimes useful to request names from another
health care provider who knows naturopathic practitioners in the community.
Some states license naturopathic physicians. As of
late 2003, those states included Hawaii, Alaska,
Washington, Oregon, Utah, Montana, Arizona,
Connecticut, New Hampshire, Vermont, Maine, and
Kansas, in addition to the territories of Puerto Rico
and the Virgin Islands. Training via a correspondence
school does not qualify a naturopath for licensure or
to take the national qualifying examination.

Precautions
A good naturopath is always willing to work with
the patient’s other physicians or health care providers.
To avoid drug interactions and to coordinate care, it is
important for a patient to inform his or her allopathic
doctor about supplements prescribed by a naturopath.
Many naturopaths give childhood vaccinations,
but some do not. If a parent is concerned about this,
it is best to go to an allopathic doctor for vaccinations.
Naturopaths are not licensed to perform major
surgery, or prescribe narcotics and antidepressant
drugs. They must involve an oncologist when treating
a cancer patient.
GALE ENCYCLOPEDIA OF MEDICINE

Although naturopathic remedies are from natural sources and pose much less risk than traditional
drugs do, there are some side effects with the use of
some. One problem they can pose is the interaction
with prescription medicines. It is important for a
patient to inform his or her allopathic physician
about any natural remedies or herbs prescribed by a
naturopath.
It is also important to note that the U.S. Food and
Drug Administration considers medicinal herbs as
dietary supplements, not drugs, and so are not subject
to the same regulations as drugs are. Because they
come from natural sources, the active ingredients
may not always be in the same concentration from
bottle to bottle, since plants naturally vary. To guard
against using too little or too much of a natural
remedy, use herbs and supplements recommended by
a naturopath or those produced by well-respected
companies.

Research and general acceptance
Medical research in naturopathy has increased
dramatically in the United States within the last
10 years. Naturopathic research often employs case
histories, summaries of practitioners’ clinical observations, and medical records. Some U.S. studies
have also met today’s scientific gold standard; they
were double-blind and placebo-controlled. Much
naturopathic research has also been done in
Germany, France, England, India, and China.
Some mainstream medical practitioners remain
distrustful of naturopathy, however. Such problems
as health-food store employees without naturopathic
credentials giving health-related advice to customers,
or occasional rare cases of infections caused by
naturopathic injections, continue to damage the reputation of this form of alternative medicine.
Research in naturopathy tends to focus on single
treatments used by naturopaths, rather than naturopathy as a whole. In 1998, an extensive review of such
single treatment studies found that naturopathic healing methods were effective for 15 different medical
conditions, including osteoarthritis, asthma, and middle ear infections. A study of 8,341 men with damaged
heart muscles in 1996 revealed that supplementation
with niacin, a B vitamin, was associated with an
11% reduced risk of mortality over 15 years. In 1996,
a study showed St. John’s wort was as effective as
prescription antidepressants in relieving depression,
and had fewer side effects.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Clinical nutrition—The use of diet and nutritional
supplements as a way to enhance health prevent
disease.
Cryotherapy—The exposure of body tissue to
extremely cold temperatures, often by applying a
probe containing liquid nitrogen.
Herb—In naturopathy, a plant or plant derivative
or extract prescribed for health or healing.
Homeopathy—The use of diluted remedies that
have energetic rather than chemical properties.
They are prescribed according to the axiom that
‘‘like cures like.’’
Hydrotherapy—The use of water as baths, poultices, and steams to heal.
Physical manipulation—The use of deep massage,
spinal alignment, and joint manipulation to stimulate tissues.
Ultrasound—A therapy employing high frequency
sound waves.

Studies have also demonstrated benefits in the
arena of women’s health issues. In one classic 1993
study, women with cervical dysplasia or abnormal
Pap smears were treated by naturopaths with topical
applications of herbs and dietary supplements. These
medications included Bromelian, an enzyme from the
pineapple; bloodroot; marigold; and zinc chloride;
and suppositories made from herbal and nutritional
ingredients, such as echinacea, vitamin A, and vitamin
E. Thirty eight of the 43 women in the study had
normal Pap smears and normal tissue biopsies after
treatment. The study concluded that these protocols
might benefit the health of patients undergoing more
traditional treatments for cervical dysplasia, such as
cryotherapy.
Other more recent research has documented the
benefits of such nutritional foods as soy in relieving
hot flashes and vaginal dryness. Nutritional supplements prescribed by naturopaths to enhance women’s
health during menopause have also proven effective;
in general, naturopathy appears to be as useful as
conventional medicine for treating menopausal symptoms. Research shows vitamin E supplements are
helpful for 50% of postmenopausal women with thinning vaginal tissue. Studies also reveal that bioflavonoids with vitamin C and gamma-oryzanol, a
2591

Naturopathic medicine

Side effects

Nausea and vomiting

substance taken from rice bran oil, can relieve hot
flashes.
Another area of women’s health concerns that
naturopathy has taken seriously is a growing preference for skin care and beauty products derived from
natural sources rather than from chemical laboratories. Such products are often more beneficial to the
skin and less likely to cause rashes or other allergic
reactions.
Resources
BOOKS

Better Homes and Gardens. Smart Choices in Alternative
Medicine. Meredith Books, 1999.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine.
Simon and Schuster, 2000.
PERIODICALS

Cramer, E. H., P. Jones, N. L. Keenan, and B. L. Thompson.
‘‘Is Naturopathy as Effective as Conventional Therapy
for Treatment of Menopausal Symptoms?’’ Journal of
Alternatie and Complementary Medicine 9 (August
2003): 529–538.
Engelhart, S., F. Saborowski, M. Krakau, et al. ‘‘Severe
Serratia liquefaciens Sepsis Following Vitamin C
Infusion Treatment by a Naturopathic Practitioner.’’
Journal of Clinical Microbiology 41 (August 2003):
3986–3988.
Hudson, Tori. ‘‘Naturopathic Medicine, Integrative
Medicine and Women’s Health.’’ Townsend Letter for
Doctors and Patients November 2001: 136.
Hudson, Tori, N.D. ‘‘Six Paths to Menopausal Wellness.’’
Herbs for Health January–February 2000: 47–50.
Lee, A. C., and K. J. Kemper. ‘‘Homeopathy and
Naturopathy: Practice Characteristics and Pediatric
Care.’’ Archives of Pediatric and Adolescent Medicine
154, no. 1 (January 2000): 75–80.
Mills, E., R. Singh, M. Kawasaki, et al. ‘‘Emerging Issues
Associated with HIV Patients Seeking Advice from
Health Food Stores.’’ Canadian Journal of Public
Health 94 (September–October 2003): 363–366.
ORGANIZATIONS

Nausea and vomiting
Definition
Nausea is the sensation of being about to vomit.
Vomiting, or emesis, is the expelling of undigested
food through the mouth.

Description
Nausea is a reaction to a number of causes that
include overeating, infection, or irritation of the throat
or stomach lining. Persistent or recurrent nausea and
vomiting should be checked by a doctor.
A doctor should be called if nausea and vomiting
occur:


after eating rich or spoiled food or taking a new
medication



repeatedly or for 48 hours or longer



following intense dizziness

It is important to see a doctor if nausea and
vomiting are accompanied by:


yellowing of the skin and whites of the eyes



pain in the chest or lower abdomen



trouble with swallowing or urination



dehydration or extreme thirst



drowsiness or confusion



constant, severe abdominal pain



a fruity breath odor

A doctor should be notified if vomiting is heavy
and/or bloody, if the vomitus looks like feces, or if the
patient has been unable to keep food down for 24
hours.
An ambulance or emergency response number
should be called immediately if:

The American Association of Naturopathic Physicians. 601
Valley Street, Suite 105, Seattle, WA 98109. (206) 2980126. <http://www.naturopathic.org>.
Naturopathic Physicians Licensing Examination Board
(NPLEX). P. O. Box 69657, Portland, OR 97201. (503)
250-9141. <http://www.nabne.org/html/
index2.html>.



Diabetic shock is suspected



Nausea and vomiting continue after other symptoms
of viral infection have subsided



The patient has a severe headache



The patient is sweating and having chest pain and
trouble breathing

Barbara Boughton
Rebecca J. Frey, PhD



The patient is known or suspected to have swallowed
a drug overdose or poisonous substance



The patient has a high body temperature, muscle
cramps, and other signs of heat exhaustion or heat
stroke

Naturopathy see Naturopathic medicine
2592

GALE ENCYCLOPEDIA OF MEDICINE

Nausea, vomiting, and breathing problems occur
after exposure to a known allergen

Causes and symptoms
Persistent, unexplained, or recurring nausea and
vomiting can be symptoms of a variety of serious illnesses. It can be caused by simply overeating or drinking too much alcohol. It can be due to stress, certain
medications, or illness. For example, people who are
given morphine or other opioid medications for pain
relief after surgery sometimes feel nauseated by the
drug. Such poisonous substances as arsenic and
other heavy metals cause nausea and vomiting.
Morning sickness is a consequence of pregnancyrelated hormone changes. Motion sickness can be
induced by traveling in a vehicle, plane, or on a boat.
Many patients experience nausea after eating spoiled
food or foods to which they are allergic. Patients who
suffer migraine headache often experience nausea.
Cancer patients on chemotherapy are nauseated.
Gallstones, gastroenteritis and stomach ulcer may
cause nausea and vomiting. These symptoms should
be evaluated by a physician.
Nausea and vomiting may also be psychological
in origin. Some people vomit under such conditions of
emotional stress as family arguments, academic tests,
airplane travel, losing a job, and similar high-stress
situations. In addition, some eating disorders are characterized by self-induced vomiting.

Diagnosis
Diagnosis is based on the severity, frequency, and
duration of symptoms, and other factors that could
indicate the presence of a serious illness.
Diagnosis is based on the taking of a careful
patient history. In some cases, the doctor may order
laboratory tests or imaging studies to determine the
presence of drugs or poisonous substances in the
patient’s blood or urine, or evidence of head injuries
or abnormalities in the digestive tract. If the nausea
and vomiting appear to be related to anxiety, stress, or
an eating disorder, the doctor may refer the patient to
a psychiatrist for further evaluation.

Vomiting relieves nausea right away but can cause
dehydration. Sipping clear juices, weak tea, and some
sports drinks help replace lost fluid and minerals without irritating the stomach. Food should be reintroduced gradually, beginning with small amounts of
dry, bland food like crackers and toast.
Medications that are given to relieve nausea and
vomiting are called antiemetics. Meclizine (Bonine), a
medication for motion sickness, also diminishes the
feeling of queasiness in the stomach. Dimenhydrinate
(Dramamine), another motion-sickness drug, is not
effective on other types of nausea and may cause
drowsiness.
Newer drugs that have been developed to treat
postoperative or postchemotherapy nausea and
vomiting include ondansetron (Zofran) and granisetron (Kytril). Another treatment that has been found
to lower the risk of nausea after surgery is intravenous
administration of supplemental fluid before the
operation.

Alternative treatment
Advocates of alternative treatments suggest biofeedback, acupressure and the use of herbs to calm the
stomach. Biofeedback uses exercise and deep relaxation to control nausea. Acupressure (applying pressure to specific areas of the body) can be applied by
wearing a special wristband or by applying firm pressure to:


the back of the jawbone



the webbing between the thumb and index finger



the top of the foot



the inside of the wrist



the base of the rib cage

Acupuncture is another alternative treatment
found to be effective in relieving nausea. A few people,
however, experience nausea as a side effect of
acupuncture.
Chamomile (Matricaria recutita) or lemon balm
(Melissa officinalis) tea may relieve symptoms.
Ginger (Zingiber officinale), another natural remedy,
can be drunk as tea or taken as candy or powered
capsules.

Treatment
Getting a breath of fresh air or getting away from
whatever is causing the nausea can solve the problem.
Eating olives or crackers or sucking on a lemon can
calm the stomach by absorbing acid and excess fluid.
Coke syrup is another proven remedy.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Massage, meditation, yoga, and other relaxation
techniques can help prevent stress-induced nausea.
Anti-nausea medication taken before traveling can
prevent motion sickness. Sitting in the front seat,
2593

Nausea and vomiting



Nausea and vomiting
These illustrations depict the mechanism and causes of vomiting in the human body. An impulse from the brain stimulates the
vomiting center (top center) in the brain stem. Nerve impulses sent to the stomach, diaphragm, and abdominal wall (bottom
center) result in stomach’s contents being expelled. Other causes of vomiting include raised pressure in the skull due to injury
or tumor (upper right), and hormonal changes during pregnancy. (Illustration by John Bavosi, Custom Medical Stock Photo.
Reproduced by permission.)

KEY TERMS
Acupuncture—A treatment technique associated
with traditional Chinese medicine, in which thin
needles are inserted into specific points located
along energy channels in the human body known
as meridians.
Antiemetic—A preparation or medication that
relieves nausea and vomiting. Coke syrup, ginger,
and motion sickness medications are examples of
antiemetics.
Dehydration—Loss of fluid and minerals following
vomiting, prolonged diarrhea, or excessive sweating.
Diabetic coma—Reduced level of consciousness
that requires immediate medical attention.
Emesis—The medical term for vomiting.

2594

focusing on the horizon, and traveling after dark can
also minimize symptoms.
Food should be fresh, properly prepared, and
eaten slowly. Overeating, tight-fitting clothes, and
strenuous activity immediately after a meal should be
avoided.
Vomiting related to emotional upsets may be
avoided by forms of psychotherapy that teach patients
to manage stress in healthier ways.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, DC: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Functional Vomiting.’’ Section 3, Chapter 21
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Ali, S. Z., A. Taguchi, B. Holtmann, and A. Kurz. ‘‘Effect of
Supplemental Pre-Operative Fluid on Postoperative
Nausea and Vomiting.’’ Anaesthesia 58 (August 2003):
780–784.
Cepeda, M. S., J. T. Farrar, M. Baumgarten, et al.
‘‘Side Effects of Opioids During Short-Term
Administration: Effect of Age, Gender,
and Race.’’ Clinical Pharmacology and
Therapeutics 74 (August 2003):
102–112.
Chung, A., L. Bui, and E. Mills. ‘‘Adverse Effects of
Acupuncture. Which Are Clinically Significant?’’
Canadian Family Physician 49 (August 2003):
985–989.
O’Brien, C. M., G. Titley, and P. Whitehurst. ‘‘A
Comparison of Cyclizine, Ondansetron and Placebo as
Prophylaxis Against Postoperative Nausea and
Vomiting in Children.’’ Anaesthesia 58 (July 2003):
707–711.
Quinla, J. D., and D. A. Hill. ‘‘Nausea and Vomiting of
Pregnancy.’’ American Family Physician 68 (July 1, 2003):
121–128.
Ratnaike, R. N. ‘‘Acute and Chronic Arsenic Toxicity.’’
Postgraduate Medical Journal 79 (July 2003):
391–396.
Tan, M. ‘‘Granisetron: New Insights Into Its Use for the
Treatment of Chemotherapy-Induced Nausea and
Vomiting.’’ Expert Opinion in Pharmacotherapy 4
(September 2003): 1563–1571.
Tiwari, A., S. Chan, A. Wong, et al. ‘‘Severe Acute
Respiratory Syndrome (SARS) in Hong Kong:
Patients’ Experiences.’’ Nursing Outlook 51
(September-October 2003): 212–219.
Walling, Anne D. ‘‘Ginger Relieves Nausea and Vomiting
During Pregnancy.’’ American Family Physician 64
(November 15, 2001): 1745.
ORGANIZATIONS

American Gastroenterological Association (AGA). 7910
Woodmont Ave., 7th Floor, Bethesda, MD 20814.
(310) 654-2055. <http://www.gastro.org/index.html>.
aga001@aol.com.

Maureen Haggerty
Rebecca J. Frey, PhD

Nberg disease see Osteopetroses
NCV see Electromyography
GALE ENCYCLOPEDIA OF MEDICINE

Near-drowning
Definition
Near-drowning is the term for survival after suffocation caused by submersion in water or another
fluid. Some experts exclude from this definition cases
of temporary survival that end in death within 24
hours, which they prefer to classify as drownings.

Description
An estimated 15,000–70,000 near-drownings
occur in the United States each year (insufficient
reporting prevents a better estimate). The typical victim is young and male. Nearly half of all drownings
and near-drownings involve children less than four
years old. Home swimming pools pose the greatest
risk for children, being the site of 60–90% of drownings in the 0–4 age group. Teenage boys also face
a heightened risk of drowning and near-drowning,
largely because of their tendency to behave recklessly
and use drugs and alcohol (drugs and alcohol are
implicated in 40–50% of teenage drownings). Males,
however, predominate even in the earliest age-groups,
possibly because young boys are often granted more
freedom from supervision than young girls enjoy,
making it more likely that they will stumble into danger and less likely that they will attract an adult’s
attention in time for a quick rescue. Roughly four
out of five drowning victims are males.

Causes and symptoms
The circumstances leading to near-drownings
(and drownings also) cannot be reduced to a single
scenario involving nonswimmers accidentally entering
deep water. On many occasions, near-drownings are
secondary to an event such as a heart attack that
causes unconsciousness or a head or spinal injury
that prevents a diver from resurfacing. Near-drownings, moreover, can occur in shallow as well as deep
water. Small children have drowned or almost
drowned in bathtubs, toilets, industrial-size cleaning
buckets, and washing machines. Bathtubs are especially dangerous for infants six months to one year
old, who can sit up straight in a bathtub but may
lack the ability to pull themselves out of the water if
they slip under the surface.
A reduced concentration of oxygen in the blood
(hypoxemia) is common to all near-drownings.
Human life, of course, depends on a constant supply
of oxygen-laden air reaching the blood by way of the
2595

Near-drowning

In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine,
Part I: Western Herbal Medicine. New York: Simon
and Schuster, 2002.

Near-drowning

lungs. When drowning begins, the larynx (an air passage) closes involuntarily, preventing both air and
water from entering the lungs. In 10–15% of cases,
hypoxemia results because the larynx stays closed.
This is called ‘‘dry drowning.’’ Hypoxemia also occurs
in ‘‘wet drowning,’’ the 85–90% of cases where the
larynx relaxes and water enters the lungs. The physiological mechanisms that produce hypoxemia in wet
drowning are different for freshwater and saltwater,
but only a small amount of either kind of water is
needed to damage the lungs and interfere with the
body’s oxygen intake. All of this happens very quickly:
within three minutes of submersion most people are
unconscious, and within five minutes the brain begins
to suffer from lack of oxygen. Abnormal heart
rhythms (cardiac dysrhythmias) often occur in neardrowning cases, and the heart may stop pumping (cardiac arrest). An increase in blood acidity (acidosis) is
another consequence of near-drowning, and under
some circumstances near-drowning can cause a substantial increase or decrease in the volume of circulating blood. Many victims experience a severe drop in
body temperature (hypothermia).
The signs and symptoms of near-drowning can
differ widely from person to person. Some victims
are alert but agitated, while others are comatose.
Breathing may have stopped, or the victim may be
gasping for breath. Bluish skin (cyanosis), coughing,
and frothy pink sputum (material expelled from the
respiratory tract by coughing) are often observed.
Rapid breathing (tachypnea), a rapid heart rate
(tachycardia), and a low-grade fever are common during the first few hours after rescue. Conscious victims
may appear confused, lethargic, or irritable.

Diagnosis
Diagnosis relies on a physical examination of the
victim and on a wide range of tests and other procedures. Blood is taken to measure oxygen levels and for
many other purposes. Pulse oximetry, another way of
assessing oxygen levels, involves attaching a device
called a pulse oximeter to the patient’s finger. An
electrocardiograph is used to monitor heart activity.
X rays can detect head and neck injuries and excess
tissue fluid (edema) in the lungs.

Treatment
Treatment begins with removing the victim from
the water and performing cardiopulmonary resuscitation (CPR). One purpose of CPR—which, of course,
should be attempted only by people trained in its use—
is to bring oxygen to the lungs, heart, brain, and other
2596

organs by breathing into the victim’s mouth. When the
victim’s heart has stopped, CPR also attempts to get the
heart pumping again by pressing down on the victim’s
chest. After CPR has been performed and emergency
medical help has arrived on the scene, oxygen is administered to the victim. If the victim’s breathing has
stopped or is otherwise impaired, a tube is inserted
into the windpipe (trachea) to maintain the airway
(this is called endotracheal intubation). The victim is
also checked for head, neck, and other injuries, and
fluids are given intravenously. Hypothermia cases
require careful handling to protect the heart.
In the emergency department, victims continue
receiving oxygen until blood tests show a return to
normal. About one-third are intubated and initially
need mechanical support to breathe. Rewarming is
undertaken when hypothermia is present. Victims
may arrive needing treatment for cardiac arrest or cardiac dysrhythmias. Comatose patients present a special
problem: although various treatment approaches have
been tried, none have proved beneficial. Patients can be
discharged from the emergency department after four
to six hours if their blood oxygen level is normal and no
signs or symptoms of near-drowning are present. But
because lung problems can arise 12 or more hours after
submersion, the medical staff must first be satisfied that
the patients are willing and able to seek further medical
help if necessary. Admission to a hospital for at least 24
hours for further observation and treatment is a must
for patients who do not appear to recover fully in the
emergency department.

Prognosis
Neurological damage is the major long-term concern in the treatment of near-drowning victims. Patients
who arrive at an emergency department awake and
alert usually survive with brain function intact, as do
about 90% of those who arrive mentally impaired
(lethargic, confused, and so forth) but not comatose.
Death or permanent neurological damage is very likely
when patients arrive comatose. Early rescue of neardrowning victims (within five minutes of submersion)
and prompt CPR (within less than 10 minutes of submersion) seem to be the best guarantees of a complete
recovery. An analysis of 715 patients admitted to
emergency departments in 1971–81 revealed that 69%
recovered completely, 25% died, and 6% survived but
suffered permanent neurological damage.

Prevention
Prevention depends on educating parents, other
adults, and teenagers about water safety. Parents must
GALE ENCYCLOPEDIA OF MEDICINE

Pool owners—and, indeed, all other adults—
should consider learning CPR. Everyone, of course,
should follow the rules for safe swimming and boating.
Those who have a medical condition that can cause a
seizure or otherwise threaten safety in the water are
advised always to swim with a partner. And of course,
people need to be aware that alcohol and drug use
substantially increase the chances of an accident.
The danger of alcohol and drug use around water
is a point that requires special emphasis where teenagers are concerned. Teenagers can also benefit from
CPR training and safe swimming and boating
classes.
Resources
BOOKS

Modell, Jerome H. ‘‘Drowning and Near-Drowning.’’ In
Harrison’s Principles of Internal Medicine, edited by
Anthony S. Fauci, et al. New York:McGraw-Hill, 1997.

Howard Baker

Nearsightedness see Myopia

Description
Necrotizing enterocolitis develops in approximately 10% of newborns weighing less than 800 g
(under 2 lbs). It is a serious infection that can produce
complications in the intestine itself—such as ulcers,
perforations (holes) in the intestinal wall, and tissue
necrosis—as well as progress to life-threatening septicemia. Necrotizing enterocolitis most commonly
affects the lower portion of the small intestine
(ileum). It is less common in the colon and upper
small bowel.

Causes and symptoms
The cause of necrotizing enterocolitis is not clear.
It is believed that the infection usually develops after
the bowel wall has already been weakened or damaged
by a lack of oxygen, predisposing it to bacterial invasion. Bacteria proliferate in the bowel and cause a deep
infection that can kill bowel tissue and spread to the
bloodstream.
Necrotizing enterocolitis almost always occurs in
the first month of life. Infants who require tube feedings may have an increased risk for the disorder. A
number of other conditions also make newborns susceptible, including respiratory distress syndrome, congenital heart problems, and episodes of apnea
(cessation of breathing). The primary risk factor, however, is prematurity. Not only is the immature digestive
tract less able to protect itself, but premature infants
are subjected to many stresses on the body in their
attempt to survive.
Early symptoms of necrotizing enterocolitis
include an intolerance to formula, distended and tender abdomen, vomiting, and blood (visible or not) in
the stool. One of the earliest signs may also be the need
for mechanical support of the infant’s breathing. If the
infection spreads to the bloodstream, infants may
develop lethargy, fluctuations in body temperature,
and periodically stop breathing.

Diagnosis

Necrotizing enterocolitis
Definition
Necrotizing enterocolitis is a serious bacterial
infection in the intestine, primarily of sick or premature newborn infants. It can cause the death (necrosis)
of intestinal tissue and progress to blood poisoning
(septicemia).
GALE ENCYCLOPEDIA OF MEDICINE

The key to reducing the complications of this disease is early suspicion by the physician. A series of x
rays of the bowel often reveals the progressive condition, and blood tests confirm infection.

Treatment
Over two-thirds of infants can be treated without
surgery. Aggressive medical therapy is begun as soon
as the condition is diagnosed or even suspected. Tube
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Necrotizing enterocolitis

realize that young children who are left in or near
water without adult supervision even for a short time
can easily get into trouble, not just at the beach or next
to a swimming pool, but in bathtubs and around
toilets, buckets, washing machines, and other household articles where water can collect. Research on
swimming pool drownings involving young children
shows that the victims have usually been left unattended less than five minutes before the accident.
Experts consider putting up a fence around a home
swimming pool an essential precaution, and estimate
that 50–90% of child drownings and near-drownings
could be prevented if fences were widely adopted. The
fence should be at least five feet high and unclimbable,
have a self-closing and self-locking gate, and completely surround the pool.

Necrotizing enterocolitis

feedings into the gastrointestinal tract (enteral nutrition) are discontinued, and tube feedings into the veins
(parenteral nutrition) are used instead until the condition has resolved. Intravenous fluids are given for
several weeks while the bowel heals.
Some infants are placed on a ventilator to help
them breathe, and some receive transfusions of platelets, which help the blood clot when there is internal
bleeding. Antibiotics are usually given intravenously
for at least 10 days. These infants require frequent
evaluations by the physician, who may order multiple
abdominal x rays and blood tests to monitor their
condition during the illness.
Sometimes, necrotizing enterocolitis must be treated with surgery. This is often the case when an infant’s
condition does not improve with medical therapy or
there are signs of worsening infection.
The surgical treatment depends on the individual
patient’s condition. Patients with infection that has
caused serious damage to the bowel may have portions
of the bowel removed. It is sometimes necessary to
create a substitute bowel by making an opening (ostomy) into the abdomen through the skin, from which
waste products are discharged temporarily. But many
physicians are avoiding this and operating to remove
diseased bowel and repair the defect at the same time.
Postoperative complications are common, including wound infections and lack of healing, persistent
sepsis and bowel necrosis, and a serious internal bleeding disorder known as disseminated intravascular
coagulation.

Prognosis
Necrotizing enterocolitis is the most common
cause of death in newborns undergoing surgery. The
average mortality is 30–40%, even higher in severe
cases.
Early identification and treatment are critical to
improving the outcome for these infants. Aggressive
nonsurgical support and careful timing of surgical
intervention have improved overall survival; however,
this condition can be fatal in about one-third of cases.
With the resolution of the infection, the bowel may
begin functioning within weeks or months. But infants
need to be carefully monitored by a physician for years
because of possible future complications.
About 10–35% of all survivors will eventually
develop a stricture, or narrowing, of the intestine
that occurs with healing. This can create an intestinal
obstruction that will require surgery. Infants may also
be more susceptible to future bacterial infections in the
2598

KEY TERMS
Enteral nutrition—Liquid nutrition provided
through tubes that enter the gastrointestinal tract,
usually through the mouth or nose.
Necrosis—The death of cells, a portion of tissue, or
a portion of an organ due to permanent damage of
some sort, such as a lack of oxygen supply to the
tissues.
Parenteral nutrition—Liquid nutrition provided
through tubes that are placed in the veins.
Sepsis—The presence of pus-forming or other disease-causing organisms in the blood or tissues.
Septicemia, commonly known as blood poisoning,
is a common type of sepsis.

gastrointestinal tract and to a delay in growth. Infants
with severe cases may also suffer neurological
impairment.
The most serious long-term gastrointestinal complication associated with necrotizing enterocolitis is
short-bowel, or short-gut, syndrome. This refers to a
condition that can develop when a large amount of
bowel must be removed, making the intestines less able
to absorb certain nutrients and enzymes. These infants
gradually evolve from tube feedings to oral feedings,
and medications are used to control the malabsorption, diarrhea, and other consequences of this
condition.

Prevention
In very small or sick premature infants, the risk
for necrotizing enterocolitis may be diminished by
beginning parenteral nutrition and delaying enteral
feedings for several days to weeks.
Some have suggested that breast milk provides
substances that may be protective, but there is no
evidence that this reduces the risk of infection. A
large multicenter trial showed that steroid drugs
given to women in preterm labor may protect their
offspring from necrotizing enterocolitis.
Sometimes necrotizing enterocolitis occurs in
clusters, or outbreaks, in hospital newborn (neonatal)
units. Because there is an infectious element to the
disorder, infants with necrotizing enterocolitis may
be isolated to avoid infecting other infants. Persons
caring for these infants must also employ strict measures to prevent spreading the infection.
GALE ENCYCLOPEDIA OF MEDICINE

Neonatal jaundice

Resources
OTHER

Neonatology on the Web. <http://www.neonatology.org>.

Caroline A. Helwick

Necrotizing fasciitis see Flesh-eating disease
Neisseria gonorrheae infection see
Gonorrhea
Neisseria meningitidis bacteremia see
Meningococcemia
Nelfinavir see Protease inhibitors

Neonatal jaundice
Definition
Neonatal jaundice (or hyperbilirubinemia) is a
higher-than-normal level of bilirubin in the blood.
Bilirubin is a by-product of the breakdown of red
blood cells. This condition can cause a yellow discoloration of the skin and the whites of the eyes called
jaundice.

Description
Bilirubin, a by-product of the breakdown of hemoglobin (the oxygen-carrying substance in red blood
cells), is produced when the body breaks down old red
blood cells. Normally, the liver processes the bilirubin
and excretes it in the stool. Hyperbilirubinemia means
there is a high level of bilirubin in the blood. This
condition is particularly common in newborn infants.
Before birth, an infant gets rid of bilirubin through the
mother’s blood and liver systems. After birth, the
baby’s liver has to take over processing bilirubin on its
own. Almost all newborns have higher than normal
levels of bilirubin. In most cases, the baby’s systems
continue to develop and can soon process bilirubin.
However, some infants may need medical treatment
to prevent serious complications which can occur due
to the accumulation of bilirubin.

Causes and symptoms
In newborn infants, the liver and intestinal systems are immature and cannot excrete bilirubin as fast
as the body produces it. This type of hyperbilirubinemia can cause jaundice to develop within a few days
after birth. About one-half of all newborns develop
GALE ENCYCLOPEDIA OF MEDICINE

A newborn baby undergoes phototherapy with visible blue
light to treat his jaundice. (Photograph by Ron Sutherland,
Photo Researchers, Inc. Reproduced by permission.)

jaundice, while premature infants are much more
likely to develop it. Hyperbilirubinemia is also more
common in some populations, such as Native
American and Asian. All infants with jaundice should
be evaluated by a health care provider to rule out more
serious problems.
Hyperbilirubinemia and jaundice can also be the
result of other diseases or conditions. Hepatitis, cirrhosis of the liver, and mononucleosis are diseases that
can affect the liver. Gallstones, a blocked bile duct, or
the use of drugs or alcohol can also cause jaundice.
Extremely high levels of bilirubin in infants may
cause kernicterus, a form of brain damage. Signs of
severe hyperbilirubinemia include listlessness, highpitched crying, apnea (periods of not breathing), arching
of the back, and seizures. If severe hyperbilirubinemia is
not treated, it can cause mental retardation, hearing loss,
behavior disorders, cerebral palsy, or death.
2599

Nephrectomy

KEY TERMS
Bilirubin—A yellowish-brown substance in the
blood that forms as old red blood cells are broken
down.
Hemoglobin—A protein, an oxygen-carrying pigment of the erythrocyte (red blood cell) formed in
the bone marrow.

are usually no long-term effects on the child from the
hyperbilirubinemia or the phototherapy. It is very rare
that a baby may need a blood transfusion for treatment of this condition.

Prevention

Jaundice—A yellow discoloration of the skin and
whites of the eyes.

There is no way to predict which infants will be
affected by hyperbilirubinemia. Newborns should be
breastfed or given formula frequently, and feedings
should begin as soon as possible after delivery to
increase activity of the baby’s digestive system.

Kernicterus—A serious condition where high bilirubin levels cause brain damage in infants.

Resources
OTHER

Diagnosis
The initial diagnosis of hyperbilirubinemia is based
on the appearance of jaundice at physical examination.
The child is often placed by an open window so he/she
may be checked in natural light. Blood samples may be
taken to determine the bilirubin level in the blood.

Treatment
Most cases of newborn jaundice resolve without
medical treatment within two to three weeks, but
should be checked by the health care provider. It is
important that the infant is feeding regularly and having normal bowel movements. If bilirubin levels are
extremely high, the infant may be treated with phototherapy—exposure of the baby’s skin to fluorescent
light. The bilirubin in the baby’s skin absorbs the
light and is changed to a substance that can be
excreted in the urine. This treatment can be done in
the hospital and is often done at home with special
lights which parents can rent for the treatment.
Treatment may be needed for several days before bilirubin levels in the blood return to normal. The baby’s
eyes are shielded to prevent the optic nerves from
absorbing too much light. Another type of treatment
uses a special fiberoptic blanket. There is no need to
shield the baby’s eyes with this treatment, and it can be
done at home. In rare cases, where bilirubin levels are
extremely high, the baby may need to receive a blood
transfusion.

D’Alessandro, Hellen Anne. Biliary Atresia. The Virtual
Hospital Page. University of Iowa. <http://
www.vh.org/Providers/Textbooks/ElectricGiNucs/
Text/BiliaryAtresia.html>.
‘‘Jaundice/Hyperbilirubinemia.’’ <http://
www2.medsch.wisc.edu/childrenshosp/
Parents_of_Preemies/jaundice.html>
‘‘Jaundice in Newborn (Hyperbilirubinemia).’’ <http://
www.ivillage.com>.
‘‘Neonatal Jaundice.’’ <http://www.gi.vghtc.gov.tw/
Teaching/Biliary/Jaundice/s13.htm>.
‘‘Neonatology on the Web.’’ <http://www.neonatology.org>.

Altha Roberts Edgren

Nephrectomy
Definition
Nephrectomy is the surgical procedure of removing a kidney or section of a kidney.

Purpose
Nephrectomy, or kidney removal, is performed on
patients with cancer of the kidney (renal cell carcinoma); a disease in which cysts (sac-like structures)
displace healthy kidney tissue (polycystic kidney disease); and serious kidney infections. It is also used to
remove a healthy kidney from a donor for the purposes of kidney transplantation.

Prognosis
Most infants with hyperbilirubinemia and associated jaundice recover without medical treatment.
Phototherapy is very effective in reducing bilirubin
levels in the majority of infants who need it. There
2600

Precautions
Because the kidney is responsible for filtering wastes
and fluid from the bloodstream, kidney function is critical
to life. Nephrectomy candidates suffering from serious
GALE ENCYCLOPEDIA OF MEDICINE

Description
Nephrectomy may involve removing a small portion of the kidney or the entire organ and surrounding
tissues. In partial nephrectomy, only the diseased or
infected portion of the kidney is removed. Radical
nephrectomy involves removing the entire kidney, a
section of the tube leading to the bladder (ureter), the
gland that sits atop the kidney (adrenal gland), and
the fatty tissue surrounding the kidney. A simple
nephrectomy performed for transplant purposes
requires removal of the kidney and a section of the
attached ureter. A similar procedure is used to harvest
cadaver kidneys, although both kidneys are typically
removed at once (bilateral nephrectomy) and blood
and cell samples for tissue typing are also taken.
The nephrectomy patient is administered general
anesthesia and the surgeon makes an incision on the
side or front of the abdomen. Muscle, fat, and tissue
are cut away to reveal the kidney. The blood vessels
connecting the kidney to the circulation are cut and
clamped. Depending on the type of nephrectomy procedure being performed, the ureter, adrenal gland,
and/or surrounding tissue may also be cut. The vessels
and the ureter in the patient are then tied off and the
incision is sewn up (sutured). The surgical procedure
can take up to three hours, depending on the type of
nephrectomy being performed.
Laparoscopic nephrectomy is a form of minimallyinvasive surgery that utilizes instruments on long,
narrow rods to view, cut, and remove the kidney. The
surgeon views the kidney and surrounding tissue with a
flexible videoscope. The videoscope and surgical instruments are maneuvered through four small incisions in
the abdomen. Once the kidney is freed, it is secured in a
bag and pulled through a fifth incision, approximately 3
in (7.6 cm) wide, in the front of the abdominal wall
below the navel. Although this surgical technique
takes slightly longer than a traditional nephrectomy,
preliminary studies have shown that it promotes a faster recovery time, shorter hospital stays, and less postoperative pain for kidney donors.

Preparation
Prior to surgery, blood samples will be taken from
the patient to type and crossmatch in case transfusion
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cadaver kidney—A kidney from a brain-dead
organ donor used for purposes of kidney
transplantation.
Polycystic kidney disease—A hereditary kidney
disease that causes fluid- or blood-filled pouches
of tissue called cysts to form on the tubules of the
kidneys. These cysts impair normal kidney
function.
Renal cell carcinoma—Cancer of the kidney.

is required during surgery. A catheter will also be
inserted into the patient’s bladder. The surgical procedure will be described to the patient, along with the
possible risks.

Aftercare
Nephrectomy patients may experience considerable discomfort in the area of the incision. Patients
may also experience numbness, caused by severed
nerves, near or on the incision. Pain relievers are
administered following the surgical procedure and
during the recovery period on an as-needed basis.
Although deep breathing and coughing may be painful due to the proximity of the incision to the diaphragm, breathing exercises are encouraged to
prevent pneumonia. Patients should not drive an automobile for a minimum of two weeks.

Risks
Possible complications of a nephrectomy procedure include infection, bleeding (hemorrhage), and
post-operative pneumonia. There is also the risk of
kidney failure in a patient with impaired function or
disease in the remaining kidney.

Normal results
Normal results of a nephrectomy are dependent
on the purpose of the procedure and the type of
nephrectomy performed. Immediately following the
procedure, it is normal for patients to experience
pain near the incision site, particularly when coughing
or breathing deeply. Renal function of the patient is
monitored carefully after nephrectomy surgery. If the
remaining kidney is healthy, it will increase its functioning over time to compensate for the loss of the
removed kidney.
2601

Nephrectomy

kidney disease, cancer, or infection usually have few treatment choices but to undergo the procedure. However, if
kidney function is lost in the remaining kidney, the patient
will require chronic dialysis treatments or transplantation
of a healthy kidney to sustain life.

Nephritis

Length of hospitalization depends on the type of
nephrectomy procedure. Patients undergoing a
laparoscopic radical nephrectomy may be released
within two to four days after surgery. Traditional
open nephrectomy patients are typically hospitalized
for about a week. Recovery time will also vary, on
average from three to six weeks.

be responsible for up to 5% of end-stage renal disease
in men.

Diagnosis
Diagnosis of nephritis is based on:


the patient’s symptoms and medical history

Resources



physical examination

ORGANIZATIONS



laboratory tests

National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.



kidney function tests



imaging studies such as ultrasound or x rays to determine blockage and inflammation

Paula Anne Ford-Martin

Nephritic syndrome see Glomerulonephritis

Nephritis
Definition
Nephritis is inflammation of the kidney.

Description
The most prevalent form of acute nephritis is glomerulonephritis. This condition affects children and
teenagers far more often than it affects adults. It is
inflammation of the glomeruli, or small round filters
located in the kidney. Pyelonephritis affects adults more
than children, and is recognized as inflammation of the
kidney and upper urinary tract. A third type of nephritis is hereditary nephritis, a rare inherited condition.

Causes and symptoms
Acute glomerulonephritis usually develops a few
weeks after a strep infection of the throat or skin.
Symptoms of glomerulonephritis include fatigue,
high blood pressure, and swelling. Swelling is most
notable in the hands, feet, ankles and face.
Pyelonephritis usually occurs suddenly, and the
acute form of this disease is more common in adult
women. The most common cause of this form of bacterial nephritis is the backward flow of infected urine
from the bladder into the upper urinary tract. Its symptoms include fever and chills, fatigue, burning or frequent urination, cloudy or bloody urine, and aching
pain on one or both sides of the lower back or abdomen.
Hereditary nephritis can be present at birth. The
rare disease presents in many different forms and can
2602

Urinalysis can reveal the presence of:


albumin and other proteins



red and white blood cells



pus, blood, or bacteria in the urine

Treatment
Treatment of glomerulonephritis normally
includes drugs such as cortisone or cytotoxic drugs
(those that are destructive to certain cells or antigens).
Diuretics may be prescribed to increase urination. If
high blood pressure is present, drugs may be prescribed to decrease the hypertension. Iron and vitamin
supplements may be recommended if the patient
becomes anemic.
Acute pyelonephritis may require hospitalization
for severe illness. Antibiotics will be prescribed, with
the length of treatment based on the severity of the
infection. In the case of chronic pyelonephritis, a sixmonth course of antibiotics may be necessary to rid
the infection. Surgery is sometimes necessary.
Treatment of hereditary nephritis depends of the
variety of the disease and severity at the time of
treatment.

Alternative treatment
Alternative treatment of nephritis should be used
as a complement to medical care and under the supervision of a licensed practitioner. Some herbs thought
to relieve symptoms of nephritis include cleavers
(Galium spp.) and wild hydrangea.

Prognosis
Prognosis for most cases of glomerulonephritis is
generally good. Ninety percent of children recover
without complications. With proper medical
GALE ENCYCLOPEDIA OF MEDICINE

Pyelonephritis in the acute form offers a good
prognosis if diagnosed and treated early. Follow-up
urinalysis studies will determine if the patient remains
bacteria-free. If the infection is not cured or continues
to recur, it can lead to serious complications such as
bacteremia (bacterial invasion of the bloodstream),
hypertension, chronic pyelonephritis and even permanent kidney damage.
If hereditary nephritis is not detected or treated, it
can lead to complications such as eye problems, deafness or kidney failure.

Prevention
Streptococcal infections that may lead to glomerulonephritis can be prevented by avoiding exposure to
strep infection and obtaining prompt medical treatment for scarlet fever or other infection.
Pyelonephritis can best be avoided if those with a
history of urinary tract infections take care to drink
plenty of fluids, urinate frequently, and practice good
hygiene following urination.
Hereditary nephritis can not be prevented, but
research to combat the disease continues.
Resources
ORGANIZATIONS

American Kidney Fund AKF). Suite 1010,6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.
OTHER

‘‘Glomerulonephritis.’’ National Institute of Diabetes
and Digestive and Kidney Disease. <http://
www.niddk.nih.gov>.

Maureen Haggerty

Nephroblastoma see Wilms’ tumor
Nephrocarcinoma see Kidney cancer

Nephrotic syndrome
Definition
Nephrotic syndrome is a collection of symptoms
which occur because the tiny blood vessels (the
GALE ENCYCLOPEDIA OF MEDICINE

glomeruli) in the kidney become leaky. This allows
protein (normally never passed out in the urine) to
leave the body in large amounts.

Description
The glomeruli (a single one is called a glomerulus)
are tiny tufts of capillaries (the smallest type of blood
vessels). Glomeruli are located in the kidneys, where
they allow a certain amount of water and waste products to leave the blood, ultimately to be passed out of
the body in the form of urine. Normally, proteins are
unable to pass through the glomerular filter.
Nephrotic syndrome, however, occurs when this filter
becomes defective, allowing large quantities of protein
to leave the blood circulation, and pass out or the body
in the urine.
Patients with nephrotic syndrome are from all age
groups, although in children there is an increased risk
of the disorder between the ages of 18 months and four
years. In children, boys are more frequently affected;
in adults, the ratio of men to women is closer to equal.

Causes and symptoms
Nephrotic syndrome can be caused by a number
of different diseases. The common mechanism which
seems to cause damage involves the immune system.
For some reason, the immune system seems to become
directed against the person’s own kidney. The glomeruli become increasingly leaky as various substances
from the immune system are deposited within the
kidney.
A number of different kidney disorders are associated with nephrotic syndrome, including:


minimal change disease or MCD (responsible for
about 80% of nephrotic syndrome in children, and
about 20% in adults) MCD is a disorder of the
glomeruli



focal glomerulosclerosis



membranous glomerulopathy



membranoproliferative glomerulonephropathy

Other types of diseases can also result in nephrotic
syndrome. These include diabetes, sickle-cell anemia,
amyloidosis, systemic lupus erythematosus, sarcoidosis, leukemia, lymphoma, cancer of the breast, colon,
and stomach, reactions to drugs (including nonsteroidal anti-inflammatory drugs, lithium, and street heroine), allergic reactions (to insect stings, snake venom,
and poison ivy), infections (malaria, various bacteria,
hepatitis B, herpes zoster, and the virus which causes
AIDS), and severe high blood pressure.
2603

Nephrotic syndrome

treatment, symptoms usually subside within a few
weeks, or at the most, a few months.

Nephrotic syndrome

KEY TERMS
Glomeruli—Tiny tufts of capillaries which carry
blood within the kidneys. The blood is filtered by
the glomeruli. The blood then continues through
the circulatory system, but a certain amount of fluid
and specific waste products are filtered out of the
blood, to be removed from the body in the form of
urine.
Immune system—The complex system within the
body which serves to fight off harmful invaders,
such as bacteria, viruses, fungi.
Kidney failure—The inability of the kidney to
excrete toxic substances from the body.

Diagnosis
Diagnosis is based first on the laboratory examination of the urine and the blood. While the urine will
reveal significant quantities of protein, the blood will
reveal abnormally low amounts of circulating proteins.
Blood tests will also reveal a high level of cholesterol. In
order to diagnose one of the kidney disorders which
cause nephrotic syndrome, a small sample of the kidney
(biopsy) will need to be removed for examination. This
biopsy can be done with a long, very thin needle which
is inserted through the skin under the ribs.
A specimen of a nephrotic human kidney. (Custom Medical
Stock Photo. Reproduced by permission.)

The first symptom of nephrotic syndrome is often
foamy urine. As the syndrome progresses, swelling
(edema) is noticed in the eyelids, hands, feet, knees,
scrotum, and abdomen. The patient feels increasingly
weak and fatigued. Appetite is greatly decreased. Over
time, the loss of protein causes the muscles to become
weak and small (called muscle wasting). The patient
may note abdominal pain and difficulty breathing.
Because the kidneys are involved in blood pressure
regulation, abnormally low or abnormally high
blood pressure may develop.
Over time, the protein loss occurring in nephrotic
syndrome will result in a generally malnourished state.
Hair and nails become brittle, and growth is stunted.
Bone becomes weak, and the body begins to lose other
important nutrients (sugar, potassium, calcium).
Infection is a serious and frequent complication, as
are disorders of blood clotting. Acute kidney failure
may develop.
2604

Treatment
Treatment depends on the underlying disorder
which has caused nephrotic syndrome. Medications
which dampen down the immune system are a mainstay of treatment. The first choice is usually a steroid
drug (such as prednisone). Some conditions may
require even more potent medications, such as cyclophosphamide or cyclosporine. Treating the underlying
conditions (lymphoma, cancers, heroine use, infections) which have led to nephrotic syndrome will
often improve the symptoms of nephrotic syndrome
as well. Some patients will require the use of specific
medications to control high blood pressure.
Occasionally, the quantity of fluid a patient is allowed
to drink is restricted. Some patients benefit from the
use of diuretics (which allow the kidney to produce
more urine) to decrease swelling.

Prognosis
Prognosis depends on the underlying disorder.
Minimal change disease has the best prognosis of all
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.

Rosalyn Carson-DeWitt, MD

capsule into the renal tubules, about 99% of it is
taken back up as the action of the tubules allows
beneficial substances to be reabsorbed into the blood
stream. The remaining filtrate is then passed to the
bladder as urine.
When the kidneys are exposed to a toxic agent,
either accidentally or intentionally (as in a suicide
attempt), damage can occur in a number of different
ways, depending upon the agent. One toxin may
directly affect the glomerulus or the renal tubules,
causing the cells of these structures to die. Another
toxin may create other substances or conditions that
result in the same cell death. Nephrotoxic injury can
lead to acute renal failure, in which the kidneys suddenly lose their ability to function, or chronic renal
failure, in which kidney function slowly deteriorates.
If unchecked, renal failure can result in death.

Causes and symptoms

Nephrotoxic injury
Definition

Several different substances can be toxic to the
kidneys. These include:


antibiotics, primarily aminoglycosides, sulphonamides, amphotericin B, polymyxin, neomycin, bacitracin, rifampin, trimethoprim, cephaloridine,
methicillin, aminosalicylic acid, oxy- and
chlorotetracyclines



analgesics, including acetaminophen (Tylenol), all
nonsteroidal anti-inflammatory drugs (e.g. aspirin,
ibuprofen), all prostaglandin synthetase inhibitors



contrast agents used in some diagnostic tests, such as
sodium iodide



heavy metals, such as lead, mercury, arsenic, and
uranium



anti-cancer drugs, such as cyclosporin, cisplatin, and
cyclophosphamide



methemoglobin-producing agents



solvents and fuels, such as carbon tetrachloride,
methanol, amyl alcohol, and ethylene glycol



herbicides and pesticides



overproduction of uric acid

Nephrotoxic injury is damage to one or both of
the kidneys that results from exposure to a toxic material, usually through ingestion.

Description
The kidneys are the primary organs of the urinary
system, which purifies the blood by removing wastes
from it and excreting them from the body in urine.
Every day, the kidneys filter about 45 gal (180 l) of
blood, about four times as much as the amount that
passes through any other organ. Because of this high
volume, the kidneys are more often exposed to toxic
substances in the blood and are very vulnerable to
injury from those sources.
Each kidney contains over one million structures
called nephrons. Each nephron consists of two parts:
the renal corpuscle and the renal tubule. The renal
corpuscle is where the blood is filtered. It is made up
of a network of capillaries (the glomerulus) and the
structure that surrounds these capillaries (Bowman’s
capsule). Blood flows into the glomerulus, where the
liquid part of the blood (plasma) passes through the
walls of the capillaries and into Bowman’s capsule
(blood cells and some proteins are too big to pass
through and therefore remain in the blood vessels).
The plasma, now called filtrate, contains substances
that the body needs, such as water, glucose, and other
nutrients, as well as wastes, excess salts, and excess
water. When the filtrate moves from Bowman’s
GALE ENCYCLOPEDIA OF MEDICINE

Nephrotoxic injury is most commonly caused by
drugs, primarily antibiotics, analgesics, and contrast
agents. In some cases, such as with aminoglycosides
and amphotericin B, the drug itself will damage the
kidneys. In others, such as with methicillin, sulphonamides, and some contrast agents, the drug provokes an
allergic reaction that destroys the kidneys. Some chemicals found in certain drugs and industrial agents
damage the kidneys by converting the hemoglobin of
2605

Nephrotoxic injury

the kidney disorders, with 90% of all patients responding to treatment. Other types of kidney diseases have
less favorable outcomes, with high rates of progression
to kidney failure. When nephrotic syndrome is caused
by another, treatable disorder (infection, allergic or
drug reaction), the prognosis is very good.

Nephrotoxic injury

red blood cells into methemoglobin, thereby interfering with the blood’s transport of oxygen. In hospitals,
the most common form of nephrotoxic injury is antibiotic nephropathy, which usually occurs when antibiotics are given to patients with already weakened
kidneys. Analgesic nephropathy is another common
form of nephrotoxic injury and occurs as a result of
long-term abuse of analgesics, usually NSAIDs (e.g.,
ibuprofen). Analgesic nephropathy is most prevalent
in women over 30. Lead nephropathy, arising from
lead poisoning, and nephropathy, from ingestion of
the solvent carbon tetrachloride, are also more common forms of nephrotoxic injury. Uric acid nephropathy is one form of nephropathy that is not caused by
exposure to an external toxin; instead, it arises from
the body’s overproduction of uric acid, usually in
persons with diseases of the lymph nodes or bone
marrow.

KEY TERMS
Bowman’s capsule—The structure surrounding the
glomerulus.
Chelate—A chemical that binds to heavy metals in
the blood, thereby helping the body to excrete
them in urine.
Contrast agent—Substance ingested so as to highlight anatomical structures in x-ray imaging tests.
Diuretic—A drug that promotes the excretion of
urine.
Glomerulus—A network of capillaries located in
the nephron where wastes are filtered from the
blood.

Risk factors for nephrotoxic injury include:

Methemoglobin—A compound formed from
hemoglobin by oxidation.
Nephron—Basic functional unit of the kidney.



Age. The elderly are more likely to overdose on antibiotics or analgesics.

Nephrotoxin—Substance that is poisonous to the
kidneys.



Underlying kidney disease. Kidneys already weakened by conditions such as diabetes can be particularly susceptible to nephrotoxic injury.



Severe dehydration.

Renal failure—Disorder characterized by the kidney’s inability to filter wastes from the blood. It may
be acute (occuring suddenly and usually reversable) or chronic (developing slowly over time as a
result of permanent damage).



Prolonged exposure to heavy metals or solvents on
the job or in the home.



Presence of diseases that cause the overproduction of
uric acid.

Symptoms of nephrotoxic injury are wide ranging
and, in some cases, depend upon the type of toxin
involved. In general, symptoms are similar to those
of renal failure and include excess urea in the blood
(azotemia), anemia, increased hydrogen ion concentration in the blood (acidosis), excess fluids in the body
(overhydration), and high blood pressure (hypertension). Blood or pus may be present in the urine, as
may uric acid crystals. A decrease in urinary output
may also occur. If the toxin’s effect on the kidneys
remains unchecked, more serious symptoms of kidney
failure may occur, including seizures and coma.

Diagnosis
Damage to the kidneys is assessed through a combination of physical examination, blood tests, urine
tests, and imaging procedures. Diagnosis of nephrotoxic injury as the underlying cause results from a
thorough investigation of the patient’s history.
Information regarding preexisting conditions, current
prescriptions, and environmental exposures to toxins
2606

aid the physician in determining what toxin, if any, has
caused the kidneys to malfunction.

Treatment
Treatment of nephrotoxic injury takes place in the
hospital and focuses on removing the toxin from the
patient’s system, while maintaining kidney function.
Removal methods are targeted to specific toxins and
may include the use of diuretics or chelates to enhance
excretion of the toxin in urine, or, in extreme cases, the
direct removal of toxins from the blood via hemodialysis or passing the blood over an absorbent substance
such as charcoal. Support of kidney function depends
on the extent of damage to the organs and ranges from
monitoring fluid levels to dialysis.

Prognosis
The outcome of nephrotoxic injury is determined
by the cause and severity of the damage. In cases where
damage has not progressed beyond acute renal failure,
kidney function can be fully restored once the toxin is
removed from the system and equilibrium restored.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Exposure to nephrotoxins can be minimized several different ways. When taking antibiotics or analgesics, recommended dosages should be strictly
followed. Also, elderly patients on these medications
(for example, those taking aspirin for heart problems
or NSAIDs for arthritis) should be closely monitored
to prevent accidental overdose. Health care workers
should be aware of any underlying conditions, such as
diabetes or allergies to antibiotics, that may heighten
the effect of a potential nephrotoxin. When using
solvents or handling heavy metals, procedures regarding their safe use should be employed.
Resources
ORGANIZATIONS

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010.<http://www.kidney.org>.

Bridget Travers

Nerve conduction velocity testing see
Electromyography
Neural hearing loss see Hearing loss

Causes and symptoms
Neuralgia is caused by irritation or nerve damage
from systemic disease, inflammation, infection, and
compression or physical irritation of a nerve. The
location of the pain depends on the underlying condition that is irritating the nerve or the location of the
particular nerve that is being irritated.
Neuralgia can result from tooth decay, poor diet,
eye strain, nose infections, or exposure to damp and
cold. Postherpetic neuralgia is an intense debilitating
pain felt at the site of a previous attack of shingles.
Trigeminal neuralgia (also called tic douloureux, the
most common type of neuralgia), causes a brief, searing pain along the trigeminal nerve, which supplies
sensation to the face. The facial pain of migraine
neuralgia lasts between 30 minutes and an hour and
occurs at the same time on successive days. The cause
is not known.
Glossopharyngeal neuralgia is an intense pain felt
at the back of the tongue, in the throat, and in the ear—
all areas served by the glossopharyngeal nerve. The
pain may occur spontaneously, or it can be triggered
by talking, eating, or swallowing (especially cold foods
such as ice cream). Its cause is not known.
Occipital neuralgia is caused by a pinched occipital nerve. There are two occipital nerves, each located
at the back of the neck, each supplying feeling to the
skin over half of the back of the head. These nerves can
be pinched due to factors ranging from arthritis to
injury, but the result is the same: numbness, pain, or
tingling over half the base of the skull.

Diagnosis

Neuralgia
Definition
Neuralgia is defined as an intense burning or stabbing pain caused by irritation of or damage to a nerve.
The pain is usually brief but may be severe. It often
feels as if it is shooting along the course of the affected
nerve.

Description
Different types of neuralgia occur depending on
the reason the nerve has been irritated. Neuralgia can
be triggered by a variety of causes, including tooth
decay, eye strain, or shingles (an infection caused by
the herpes zoster virus). Pain is usually felt in the part
of the body that is supplied by the irritated nerve.
GALE ENCYCLOPEDIA OF MEDICINE

Neuralgia is a symptom of an underlying disorder;
its diagnosis depends on finding the cause of the condition creating the pain.
To diagnose occipital neuralgia, a doctor can
inject a small amount of anesthetic into the region of
the occipital nerve. If the pain temporarily disappears,
and there are no other physical reasons for the pain,
the doctor may recommend surgery to deal with the
pinched nerve.

Treatment
Glossopharyngeal, trigeminal, and postherpetic
neuralgias sometimes respond to anticonvulsant
drugs, such as carbamazepine or phenytoin, or to
painkillers, such as acetaminophen. Trigeminal neuralgia may also be relieved by surgery in which the
nerve is cut or decompressed. In some cases,
2607

Neuralgia

However, if permanent damage has resulted in chronic
renal failure, lifelong dialysis or a kidney transplant
may be required.

Neuralgia

compression neuralgia (including occipital neuralgia)
can be relieved by surgery.
People with shingles should see a doctor within
three days of developing the rash, since aggressive
treatment of the blisters that appear with the rash
can ease the severity of the infection and minimize
the risk of developing postherpetic neuralgia.
However, it is not clear whether the treatment can
prevent postherpetic neuralgia.
If postherpetic neuralgia develops, a variety of
treatments can be tried, since their effectiveness varies
from person-to-person.


antidepressants such as amitriptyline (Elavil)



anticonvulsants
carbamazepine)



capsaicin (Xostrix), the only medication approved by
the FDA for treatment of postherpetic neuralgia



topical painkillers



desensitization



TENS (transcutaneous electrical nerve stimulation)



dorsal root zone (DREZ) surgery (a treatment of last
resort)

(phenytoin,

valproate,

or

Alternative treatment
B-complex vitamins, primarily given by intramuscular injection, can be an effective treatment. A whole
foods diet with adequate protein, carbohydrates, and
fats that also includes yeast, liver, wheat germ, and
foods that are high in B vitamins may be helpful.
Acupuncture is a very effective treatment, especially
for postherpetic neuralgia. Homeopathic treatment
can also be very effective when the correct remedy is
used. Some botanical medicines may also be useful.
For example, black cohosh (Cimicifuga racemosa)
appears to have anti-inflammatory properties based
on recent research.

Prognosis
The effectiveness of the treatment depends on the
cause of the neuralgia, but many cases respond to pain
relief.
Trigeminal neuralgia tends to come and go, but
successive attacks may be disabling. Although neuralgia is not fatal, the patient’s fear of being in pain can
seriously interfere with daily life.
Some people with postherpetic neuralgia respond
completely to treatment. Most people, however, experience some pain after treatment, and a few receive no
2608

KEY TERMS
Desensitization—A technique of pain reduction in
which the painful area is stimulated with whatever
is causing the pain.
Dorsal root entry zone (DREZ)—A type of nerve
surgery for postherpetic neuralgia that is occasionally used when the patient can get no other pain
relief. The surgery destroys the area where
damaged nerves join the central nervous system,
thereby interfering with inappropriate pain messages from nerves to the brain.
Glossopharyngeal neuralgia—Sharp recurrent pain
deep in the throat that extends to the area around
the tonsils and possibly the ear. It is triggered by
swallowing or chewing.
Migraine neuralgia—A variant of migraine pain,
also called cluster headache, in which severe
attacks of pain affect the eye and forehead on one
side of the face.
Occipital neuralgia—Pain on one side of the back
of the head caused by entrapment or pinching of an
occipital nerve.
Postherpetic neuralgia—Persistent pain that occurs
as a complication of a herpes zoster infection.
Although the pain can be treated, the response is
variable.
Shingles—A painful rash with blisters that appears
along the course of a nerve. It is caused by infection
with herpes zoster virus.
TENS—The abbreviation for transcutaneous electrical nerve stimulation, a technique used to control
chronic pain. Electrodes placed over the painful
area deliver a mild electrical impulse to nearby
nerve pathways, thereby easing pain.
Trigeminal neuralgia—Brief episodes of severe
shooting pain on one side of the face caused by
inflammation of the root of the trigeminal nerve.
Also referred to as tic douloureux.

relief at all. Some people live with this type of neuralgia
for the rest of their lives, but for most, the condition
gradually fades away within five years.
Resources
PERIODICALS

Fields, H. ‘‘Treatment of Trigeminal Neuralgia.’’ The
New England Journal of Medicine 334 (April 1996):
1125-1126.
GALE ENCYCLOPEDIA OF MEDICINE

American Chronic Pain Association. P.O. Box 850, Rocklin,
CA 95677-0850. (916) 632-0922. <http://
members.tripod.com/~widdy/ACPA.html>.
National Chronic Pain Outreach Association. P.O. Box 274,
Millboro, VA 24460. (540) 997-5004.
Trigeminal Neuralgia/Tic Douloureux Association. P.O.
Box 340, Barnegat Light, NJ 08006. (609) 361-1014.

Carol A. Turkington

Neuroblastoma
Definition
Neuroblastoma is a type of cancer that usually
originates either in the tissues of the adrenal gland or
in the ganglia of the abdomen or in the ganglia of the
nervous system. (Ganglia are masses of nerve tissue or
groups of nerve cells.) Tumors develop in the nerve
tissue in the neck, chest, abdomen, or pelvis.

Description
Neuroblastoma is one of the few cancer types
known to secrete hormones. It occurs most often in
children, and it is the third most common cancer that
occurs in children. Approximately 7.5% of the childhood cancers diagnosed in 2001 were neuroblastomas,
affecting one in 80,000 to 100,000 children in the
United States. Close to 50% of cases of neuroblastoma occur in children younger than two years old.
The disease is sometimes present at birth, but is usually
not noticed until later. By the time the disease is diagnosed, it has often spread to the lymph nodes, liver,
lungs, bones, or bone marrow. Approximately onethird of neuroblastomas start in the adrenal glands.

Demographics
According to some reports, African-American
children develop the disease at a slightly higher rate
than Caucasian children (8.7 per million compared to
8.0 per million cases diagnosed).

Causes and symptoms
The causes of neuroblastoma are not precisely
known. Current research holds that neuroblastomas
develop when cells produced by the fetus (neuroblast
cells) fail to mature into normal nerve or adrenal
cells and keep growing and proliferating. The first
GALE ENCYCLOPEDIA OF MEDICINE

symptom of a neuroblastoma is usually an unusual
growth or lump, found in most cases in the abdomen
of the child, causing discomfort or a sensation of fullness and pain. Other symptoms such as numbness and
fatigue, arise because of pressure caused by the tumor.
Bone pain also occurs if the cancer has spread to the
bone. If it has spread to the area behind the eye, the
cancer may cause protruding eyes and dark circles
around the eyes; in a few cases, blindness may be the
presenting symptom. Or paralysis may result from
compression of the spinal cord. Fever is also reported
in one case out of four. High blood pressure, persistent
diarrhea, rapid heartbeat, reddening of the skin and
sweating occur occasionally. Some children may also
have uncoordinated or jerky muscle movements, or
uncontrollable eye movements, but these symptoms
are rare. If the disease spreads to the skin, blue or
purple patches are observed.

Diagnosis
A diagnosis of neuroblastoma usually requires
blood and urine tests to investigate the nature and
quantity of chemicals (neurotransmitters) released by
the nerve cells. These are broken down by the body
and released in urine. Additionally, scanning techniques are used to confirm the diagnosis of neuroblastoma. These techniques produce images or pictures of
the inside of the body and they include computed
tomography scan (CT scan) and magnetic resonance
imaging (MRI). To confirm the diagnosis, the physician will surgically remove some of the tissue from the
tumor or bone marrow (biopsy), and examine the cells
under the microscope.

Treatment
The treatment team usually consists of an oncologist specialized in the treatment of neuroblastoma, a
surgeon to perform biopsies and possibly attempt
surgical removal of the tumor, a radiation therapy
team and, if indicated, a bone marrow transplantation
team.
Staging
Once neuroblastoma has been diagnosed, the physician will perform more tests to determine if the cancer has spread to other tissues in the body. This
process, called staging, is important for the physician
to determine how to treat the cancer and check liver
and kidney function. The staging system for neuroblastoma is based on how far the disease has spread
from its original site to other tissues in the body.
2609

Neuroblastoma

ORGANIZATIONS

Neuroblastoma

surgery; high-energy rays (radiation) are used to kill as
many of the remaining cancer cells as possible.
Chemotherapy (called adjuvant chemotherapy) may
also be used after surgery to kill remaining cells. Bone
marrow transplantation is used to replace bone marrow cells killed by radiation or chemotherapy. In some
cases the patient’s own bone marrow is removed prior
to treatment and saved for transplantation later.
Other times the bone marrow comes from a
‘‘matched’’ donor, such as a sibling.

A neuroblastoma appearing at the surface of the liver.
(Custom Medical Stock Photo. Reproduced by permission.)

Localized resectable (able to be cut out) neuroblastoma is confined to the site of origin, with no
evidence that it has spread to other tissues, and the
cancer can be surgically removed. Localized unresectable neuroblastoma is confined to the site of origin,
but the cancer cannot be completely removed surgically. Regional neuroblastoma has extended beyond
its original site, to regional lymph nodes, and/or surrounding organs or tissues, but has not spread to
distant sites in the body. Disseminated neuroblastoma
has spread to distant lymph nodes, bone, liver, skin,
bone marrow, and/or other organs. Stage 4S (or IVS,
or ‘‘special’’) neuroblastoma has spread only to liver,
skin, and/or, to a very limited extent, bone marrow.
Recurrent neuroblastoma means that the cancer has
come back, or continued to spread after it has been
treated. It may come back in the original site or in
another part of the body.
Treatments are available for children with all
stages of neuroblastoma. More than one of these treatments may be used, depending on the stage of the
disease. The four types of treatment used are:


surgery (removing the tumor in an operation)



radiation therapy (using high-energy x-rays to kill
cancer cells)



chemotherapy (using drugs to kill cancer cells)



bone marrow transplantation (replacing the patient’s
bone marrow cells with those from a healthy person)

Surgery is used whenever possible, to remove as
much of the cancer as possible, and can generally cure
the disease if the cancer has not spread to other areas
of the body. Before surgery, chemotherapy may be
used to shrink the tumor so that it can be more easily
removed during surgery; this is called neoadjuvant
chemotherapy. Radiation therapy is often used after
2610

One novel approach to treatment of neuroblastomas is therapy with desferoxamine (DFO), which is
ordinarily used to treat iron poisoning. DFO has been
shown to have antitumor activity in neuroblastomas
and other cancers of the central nervous system. It is
thought that the drug works by lowering the increased
iron levels in the body associated with cancer.
As of 2004, there are significant differences in
treatment protocols for neuroblastoma between the
major North American study group (Children’s
Oncology Group) and its European counterpart, the
Société Internationale d’Oncologie Pédiatrique
(SIOP). These differences include biopsy techniques,
the timing and extent of surgery, chemotherapy
dosages, and the types of salvage therapy employed.

Alternative treatment
No alternative therapy has yet been reported to
substitute for conventional neuroblastoma treatment.
Complementary therapies—such as retinoic acid therapy—have been shown to be beneficial to patients
when administered after a conventional course of chemotherapy or transplantation.

Prognosis
The chances of recovery from neuroblastoma
depend on the stage of the cancer, the age of the
child at diagnosis, the location of the tumor, and the
state and nature of the tumor cells evaluated under
the microscope. Infants have a higher rate of cure than
do children over one year of age, even when the disease
has spread. In general, the prognosis for a young child
with neuroblastoma is good: the predicted five-year
survival rate is approximately 85% for children who
had the onset of the disease in infancy, and 35% for
those whose disease developed later.

Prevention
Neuroblastoma may be a genetic disease passed
down from the parents. In 2004, a group of German
GALE ENCYCLOPEDIA OF MEDICINE

Adjuvant chemotherapy—Treatment of the tumor
with drugs after surgery to kill as many of the
remaining cancer cells as possible.
Adrenal gland—Gland located above each kidney
consisting of an outer wall (cortex) that produces
steroid hormones and an inner section (medulla)
that produces other important hormones, such as
adrenaline and noradrenaline.
Alternative therapy—A therapy is generally called
alternative when it is used instead of conventional
cancer treatments.
Biopsy—A small sample of tissue removed from the
site of the tumor to be examined under a
microscope.
Conventional therapy—Treatments that are widely
accepted and practiced by the mainstream medical
community.
Complementary therapy—A therapy is called
complementary when it is used in addition to conventional cancer treatments.
Disseminated—Spread to other tissues.
Hormone—A substance produced by specialized
cells that affects the way the body carries out the
biochemical and energy-producing processes
required to maintain health (metabolism.
Localized—Confined to a small area.
Neoadjuvant chemotherapy—Treatment of the
tumor with drugs before surgery to reduce the size
of the tumor.
Neuroblast cells—Cells produced by the fetus which
mature into nerve cells and adrenal medulla cells.
Monoclonal antibody—A protein substance which
is produced in the laboratory by a single population
of cells. They are being tested as a possible form of
cancer treatment.
Resectable cancer—A tumor that can be surgically
removed.
Salvage therapy—Treatment measures taken late in
the course of a disease after other therapies have
failed. It is also known as rescue therapy.
Staging system—A system based on how far the
cancer has spread from its original site, developed
to help the physician determine how best to treat
the disease.
Unresectable cancer—A tumor that cannot be
completely removed by surgery.

GALE ENCYCLOPEDIA OF MEDICINE

researchers reported that a series of neuroblastomas
demonstrated a consistent pattern of deletions and
overrepresentations on chromosomes 3, 10, 17q, and
20. There is currently no known method for its
prevention.

Special concerns
After completion of a course of treatment for
neuroblastoma, physicians sometimes recommend
that the child undergo an investigative operation.
This procedure allows the treatment team to evaluate
how effective treatment has been, and may offer an
opportunity to remove more of the tumor if it is still
present.
Resources
BOOKS

Alexander, F. ‘‘Neuroblastoma.’’ Urol. Clin. North. Am. 27,
August 2000, pp. 383-92.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Neuroblastoma.’’ Section 19, Chapter 266 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Alexander, F. ‘‘Neuroblastoma.’’ Urol. Clin. North. Am. 27
(August 2000): 383–392.
Berthold, F., and B. Hero. ‘‘Neuroblastoma: current drug
therapy recommendations as part of the total treatment
approach.’’ Drugs 59 (June 2000): 1261–1277.
Bockmuhl, U., X. You, M. Pacyna-Gengelbach, et al.
‘‘CGH Pattern of Esthesioneuroblastoma and Their
Metastases.’’ Brain Pathology 14 (April 2004): 158–163.
Dayani, P. N., M. C. Bishop, K. Plack, and P. M. Zeltzer.
‘‘Desferoxamine (DFO)—Mediated Iron Chelation:
Rationale for a Novel Approach to Therapy for Brain
Cancer.’’ Journal of Neurooncology 67 (May 2004):
367–377.
Grosfeld, J. L. ‘‘Risk-based management of solid tumors in
children.’’ American Journal of Surgery 180 (November
2000):322–327.
Lau, J. J., J. D. Trobe, R. E. Ruiz, et al. ‘‘Metastatic
Neuroblastoma Presenting with Binocular Blindness
from Intracranial Compression of the Optic Nerves.’’
Journal of Neuroophthalmology 24 (June 2004):
119–124.
Morgenstern, B. Z., A. P. Krivoshik, V. Rodriguez, and
P. M. Anderson. ‘‘Wilms’ Tumor and Neuroblastoma.’’
Acta Paediatrica Supplementum 93 (May 2004): 78–84.
Pinkerton, C., R. Blanc, M. P. Vincent, C. Bergeron,
B. Fervers, and T. Philip. ‘‘Induction chemotherapy
in metastatic neuroblastoma—does dose influence
response? A critical review of published data standards,
options and recommendations (SOR) project of the
National Federation of French Cancer Centres
2611

Neuroblastoma

KEY TERMS

Neuroendocrine tumors

(FNCLCC).’’ European Journal of Cancer 36
(September 2000): 1808–1815.
ORGANIZATIONS

The American Cancer Society. ‘‘After Diagnosis: A Guide
for Patients and Families.’’ ‘‘Caring for the Patient with
Cancer at Home.’’ ‘‘Understanding Chemotherapy: A
Guide for Patients and Families.’’ ‘‘Understanding
Radiation Therapy: A Guide for Patients and
Families.’’
National Cancer Institute. Office of Cancer
Communications, 31 Center Drive, MSC 2580,
Bethesda, MD 20892-2580. 800-422-6237. <http://
cancernet.nci.nih.gov/clinpdq/pif/
Neuroblastoma_Patient.html>.
National Institutes of Health & National Cancer Institute.
Young People With Cancer: A Handbook for Parents.
<http://www.cancernet.nci.nih.gov/young_people/
yngconts.html>.

Lisa Christenson, PhD
Monique Laberge, PhD
Rebecca J. Frey, PhD

Neuroendocrine tumors
Definition
Neuroendocrine tumor refers to the type of cell
that a tumor grows from rather than where that tumor
is located. Neuroendocrine cells produce hormones or
regulatory proteins, and so tumors of these cells
usually have symptoms that are related to the specific
hormones that they produce.

Description
Neuroendocrine cells have roles both in the endocrine system and the nervous system. They produce
and secrete a variety of regulatory hormones, or neuropeptides, which include neurotransmitters and
growth factors. When these cells become cancerous,
they grow and overproduce their specific neuropeptide. Neuroendocrine tumors are generally rare. One
type of neuroendocrine tumor is a carcinoid tumor.
This type of tumor can occur in the intestinal tract,
appendix, rectum, bronchial tubes, or ovary. Most
carcinoid tumors secrete serotonin. When the blood
concentration of this hormone is high enough, it
causes carcinoid syndrome. This syndrome refers to a
variety of symptoms that are caused by the excessive
amount of hormone secreted rather than the tumor
itself.
2612

The total incidence of neuroendocrine tumors is
thought to be between five and nine million people in
the United States. It is possible that these tumors are
underreported because they grow slowly and do not
always produce dramatic symptoms.

Causes and symptoms
Many of the symptoms of carcinoid tumor are due
to the hormones that the tumor secretes. These hormones can affect the whole body and cause what is
referred to as carcinoid syndrome. The most common
symptom of carcinoid syndrome is flushing, a sudden
appearance of redness and warmth in the face and
neck that can last from minutes to hours. Other symptoms of carcinoid syndrome are diarrhea, asthma-like
symptoms and heart problems. Since most carcinoid
tumors are found in the appendix, the symptoms are
often similar to appendicitis, primarily pain in the
abdomen. When these tumors are found in the small
intestine, they can cause abdominal pain that is often
initially diagnosed as bowel obstruction. Many
patients have no symptoms and the carcinoids are
found during routine endoscopy of the intestines.

Diagnosis
The diagnosis of carcinoid syndrome is made by
the measurement of 5–hydroxy indole acetic acid (5–
HIAA) in the urine. 5–HIAA is a breakdown (waste)
product of serotonin. If the syndrome is diagnosed,
the presence of carcinoid tumor is a given. When the
syndrome is not present, diagnosis may be delayed,
due to the vague symptoms present. Diagnosis can
sometimes take up to two years. It is made by performing a number of tests, and the specific test used
depends on the tumor’s suspected location. The tests
that may be performed include gastrointestinal endoscopy, chest x ray, computed tomography scan (CT
scan), magnetic resonance imaging, or ultrasound. A
biopsy of the tumor is performed for diagnosis. A
variety of hormones can be measured in the blood as
well to indicate the presence of a carcinoid.

Treatment
The only effective treatment for carcinoid tumor
as of the early 2000s is surgical removal of the tumor.
Although chemotherapy is sometimes used when
metastasis has occurred, it is rarely effective. The treatment for carcinoid syndrome is typically meant to
decrease the severity of symptoms. Patients should
avoid stress as well as foods that bring on the syndrome. Some medications can be given for
GALE ENCYCLOPEDIA OF MEDICINE

Appendicitis—Inflammation of the appendix.
Growth factor—A local hormone produced by
some cells that initiates growth.
Metastasis—The spread of disease from one part of
the body to another, as when cancer cells appear in
parts of the body remote from the site of the primary
tumor.
Neurotransmitter—A chemical messenger used to
transmit information in the nervous system.

symptomatic relief; for example, tumors of the gastrointestinal tract may be treated with octreotide
(Sandostatin) or lanreotide (Somatuline) to relieve
such symptoms as diarrhea and flushing. These drugs
are known as somatostatin analogs.

Ahlman, H., S. Friman, C. Cahli, et al. ‘‘Liver
Transplantation for Treatment of Metastatic
Neuroendocrine Tumors.’’ Annals of the New York
Academy of Sciences 1014 (April 2004): 265–269.
Oberg, K., L. Kvols, M. Caplin, et al. ‘‘Consensus Report on
the Use of Somatostatin Analogs for the Management
of Neuroendocrine Tumors of the
Gastroenteropancreatic System.’’ Annals of Oncology
15 (June 2004): 966–973.
Singhal, Hemant, MD, and Alan A. Saber, MD. ‘‘Carcinoid
Tumor, Intestinal.’’ eMedicine April 13, 2004. <http://
www.emedicine.com/med/topic271.htm>.
Van Gompel, J. J., R. S. Sippel, T. F. Warner, and H. Chen.
‘‘Gastrointestinal Carcinoid Tumors: Factors That
Predict Outcome.’’ World Journal of Surgery 28 (April
2004): 387–392.
ORGANIZATIONS

Carcinoid Cancer Foundation, Inc. 1751 York Ave., New
York, NY 10128. (212) 722-3132. <http://
www.carcinoid.org>.

Liver transplantation is a treatment option for
patients with neuroendocrine tumors that have metastasized only to the liver. As of 2004, this approach is
reported to offer patients long disease-free periods and
relief of symptoms.

Cindy L. A. Jones, PhD
Rebecca J. Frey, PhD

Prognosis
The prognosis of carcinoid tumors is related to the
specific growth patterns of that tumor, as well as its
location. For example, a group of researchers at the
University of Wisconsin reported in 2004 that patients
with gastrointestinal tumors in the hindgut had longer
periods of disease-free survival than those with foregut
or midgut cancers. For localized disease the five-year
survival rate can be 94%, whereas for patients where
metastasis has occurred, the average five-year survival
rate is 18%. It is not unusual for patients with carcinoid tumors to live ten or fifteen years after the initial
diagnosis.

Prevention
Neuroendocrine tumors such as carcinoid tumors
are rare, and no information consequently is yet available on cause or prevention.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Carcinoid Tumors.’’ Section 2, Chapter 17 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
GALE ENCYCLOPEDIA OF MEDICINE

Neurofibromatosis
Definition
Neurofibromatosis (NF), or von Recklinghausen
disease, is a genetic disease in which patients develop
multiple soft tumors (neurofibromas). These tumors
occur under the skin and throughout the nervous
system.

Description
Neural crest cells are primitive cells which exist
during fetal development. These cells eventually turn
into:


cells which form nerves throughout the brain, spinal
cord, and body



cells which serve as coverings around the nerves that
course through the body



pigment cells, which provide color to structures



the meninges, the thin, membranous coverings of the
brain and spinal cord



cells which ultimately develop into the bony structures of the head and neck
2613

Neurofibromatosis

PERIODICALS

KEY TERMS

Neurofibromatosis

In neurofibromatosis, a genetic defect causes these
neural crest cells to develop abnormally. This results in
numerous tumors and malformations of the nerves,
bones, and skin.
Neurofibromatosis occurs in about one of every
4,000 births. Two types of NF exist, NF-1 (90% of all
cases), and NF-2 (10% of all cases).

Causes and symptoms
Both forms of neurofibromatosis are caused by a
defective gene. NF-1 is due to a defect on chromosome
17; NF-2 results from a defect on chromosome 22.
Both of these disorders are inherited in a dominant
fashion. This means that anybody who receives just
one defective gene will have the disease. However, a
family pattern of NF is only evident for about half of
all cases of NF. The other cases of NF occur due to a
spontaneous mutation (a permanent change in the
structure of a specific gene). Once such a spontaneous
mutation has been established in an individual, however, it is then possible to be passed on to any offspring. The chance of a person with NF passing on the
NF gene to a child is 50%.
NF-1 has a number of possible signs and can be
diagnosed if any two of the following are present:


The presence of café-au-lait (French for coffee-withmilk) spots. These are patches of tan or light brown
skin, usually about 5-15 mm in diameter. Nearly all
patients with NF-1 will display these spots.



Multiple freckles in the armpit or groin area.



Ninty percent of patients with NF-1 have tiny
tumors called Lisch nodules in the iris (colored
area) of the eye.



Neurofibromas. These soft tumors are the hallmark
of NF-1. They occur under the skin, often located
along nerves or within the gastrointestinal tract.
Neurofibromas are small and rubbery, and the skin
overlying them may be somewhat purple in color.



Skeletal deformities, such as a twisted spine (scoliosis), curved spine (humpback), or bowed legs.



Tumors along the optic nerve, which cause vision
disturbance in about 20% of patients.



The presence of NF-1 in a patient’s parent, child, or
sibling.

There are very high rates of speech impairment,
learning disabilities, and attention deficit disorder
in children with NF-1. Other complications include
the development of a seizure disorder, or the abnormal
accumulation of fluid within the brain (hydrocephalus).
2614

This person’s skin has multiple soft tumors, or neurofibromas. Such tumors develop underneath the skin. (Custom
Medical Stock Photo. Reproduced by permission.)

A number of cancers are more common in patients with
NF-1. These include a variety of types of malignant
brain tumors, as well as leukemia, and cancerous
tumors of certain muscles (rhabdomyosarcoma), the
adrenal glands (pheochromocytoma), or the kidneys
(Wilms’ tumor).
Patients with NF-2 do not necessarily have the
same characteristic skin symptoms (café-au-lait
spots, freckling, and neurofibromas of the skin) that
appear in NF-1. The characteristic symptoms of NF-2
are due to tumors along the acoustic nerve. Interfering
with the function of this nerve results in the loss of
hearing; and the tumor may spread to neighboring
nervous system structures, causing weakness of the
muscles of the face, headache, dizziness, poor balance,
and uncoordinated walking. Cloudy areas on the lens
of the eye (called cataracts) frequently develop at an
unusually early age. As in NF-1, the chance of brain
tumors developing is unusually high.

Diagnosis
Diagnosis is based on the symptoms outlined
above. Diagnosis of NF-1 requires that at least two of
the listed signs are present. Diagnosis of NF-2 requires
the presence of either a mass on the acoustic nerve or
another distinctive nervous system tumor. An important
diagnostic clue for either NF-1 or NF-2 is the presence
of the disorder in a patient’s parent, child, or sibling.
GALE ENCYCLOPEDIA OF MEDICINE

Chromosome—A structure within the nucleus of
every cell, which contains genetic information governing the organism’s development.
Mutation—A permanent change to the genetic
code of an organism. Once established, a mutation
can be passed on to offspring.
Neurofibroma—A soft tumor usually located on a
nerve.
Tumor—An abnormally multiplying mass of cells.

Monitoring the progression of neurofibromatosis
involves careful testing of vision and hearing. X-ray
studies of the bones are frequently done to watch for
the development of deformities. CT scans and MRI
scans are performed to track the development/progression of tumors in the brain and along the nerves.
Auditory evoked potentials (the electric response
evoked in the cerebral cortex by stimulation of the
acoustic nerve) may be helpful to determine involvement of the acoustic nerve, and EEG (electroencephalogram, a record of electrical currents in the brain)
may be needed for patients with suspected seizures.

Treatment
There are no available treatments for the disorders which underlie either type of neurofibromatosis.
To some extent, the symptoms of NF-1 and NF-2 can
be treated individually. Skin tumors can be surgically
removed. Some brain tumors, and tumors along the
nerves, can be surgically removed, or treated with
drugs (chemotherapy) or x-ray treatments (radiation
therapy). Twisting or curving of the spine and bowed
legs may require surgical treatment, or the wearing of
a special brace.

Prognosis
Prognosis varies depending on the types of tumors
which an individual develops. As tumors grow, they
begin to destroy surrounding nerves and structures.
Ultimately, this destruction can result in blindness,
deafness, increasingly poor balance, and increasing
difficulty with the coordination necessary for walking.
Deformities of the bones and spine can also interfere
with walking and movement. When cancers develop,
prognosis worsens according to the specific type of
cancer.
GALE ENCYCLOPEDIA OF MEDICINE

There is no known way to prevent the approximately 50% of all NF cases which occur due to a
spontaneous change in the genes (mutation). New
cases of inherited NF can be prevented with careful
genetic counseling. A person with NF can be made to
understand that each of his or her offspring has a 50%
chance of also having NF. When a parent has NF, and
the specific genetic defect causing the parent’s disease
has been identified, tests can be performed on the fetus
(developing baby) during pregnancy. Amniocentesis
or chorionic villus sampling are two techniques
which allow small amounts of the baby’s cells to be
removed for examination. The tissue can then be
examined for the presence of the parent’s genetic
defect. Some families choose to use this information
in order to prepare for the arrival of a child with a
serious medical problem. Other families may choose
not to continue the pregnancy.
Resources
ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914)
428-7100. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Neurofibromatosis Foundation, Inc. 95 Pine St.,
16th Floor, New York, NY 10005. (800) 323-7938.
<http://nf.org>.
Neurofibromatosis, Inc. 8855 Annapolis Rd., #110,
Lanham, MD 20706-2924. (800) 942-6825.

Rosalyn Carson-DeWitt, MD

Neurogenic arthropathy see Charcot’s joints

Neurogenic bladder
Definition
Neurogenic bladder is a dysfunction that results
from interference with the normal nerve pathways
associated with urination.

Description
Normal bladder function is dependent on the
nerves that sense the fullness of the bladder (sensory
nerves) and on those that trigger the muscle movements that either empty it or retain urine (motor
nerves). The reflex to urinate is triggered when the
bladder fills to 300-500 ml. The bladder is then
2615

Neurogenic bladder

Prevention

KEY TERMS

Neurogenic bladder

emptied when the contraction of the bladder wall
muscles forces urine out through the urethra. The
bladder, internal sphincters, and external sphincters
may all be affected by nerve disorders that create
abnormalities in bladder function.
There are two categories of neurogenic bladder
dysfunction: overactive (spastic or hyper-reflexive)
and underactive (flaccid or hypotonic). An overactive
neurogenic bladder is characterized by uncontrolled,
frequent expulsion of urine from the bladder. There is
reduced bladder capacity and incomplete emptying of
urine. An underactive neurogenic bladder has a capacity that is extremely large (up to 2000 ml). Due to a
loss of the sensation of bladder filling, the bladder
does not contract forcefully, and small amounts of
urine dribble from the urethra as the bladder pressure
reaches a breakthrough point.

Causes and symptoms
There are numerous causes for neurogenic bladder
dysfunction and symptoms vary depending on the
cause. An overactive bladder is caused by interruptions
in the nerve pathways to the bladder occurring above
the sacrum (five fused spinal vertebrae located just
above the tailbone or coccyx). This nerve damage results
in a loss of sensation and motor control and is often seen
in stroke, Parkinson’s disease, and most forms of spinalcord injuries. An underactive bladder is the result of
interrupted bladder stimulation at the level of the sacral
nerves. This may result from certain types of surgery on
the spinal cord, sacral spinal tumors, or congenital
defects. It also may be a complication of various diseases, such as syphilis, diabetes mellitus, or polio.

Diagnosis
Neurogenic bladder is diagnosed by carefully
recording fluid intake and urinary output and by measuring the quantity of urine remaining in the bladder
after voiding (residual urine volume). This measurement is done by draining the bladder with a small
rubber tube (catheter) after the person has urinated.
Kidney function also is evaluated by regular laboratory testing of the blood and urine. Cystometry may be
used to estimate the capacity of the bladder and the
pressure changes within it. These measurements can
help determine changes in bladder compliance in order
to assess the effectiveness of treatment. Doctors may
use a cystoscope to look inside the bladder and tubes
that lead to it from the kidneys (ureters). Cystoscopy
may be used to assess the loss of muscle fibers and
elastic tissues and, in some cases, for removing small
pieces of tissue for biopsy.
2616

Treatment
Doctors begin treating neurogenic bladder by
attempting to reduce bladder stretching (distension)
through intermittent or continuous catheterization. In
intermittent catheterization, a small rubber catheter is
inserted at regular intervals (four to six times per day)
to approximate normal bladder function. This avoids
the complications that may occur when a catheter
remains in the bladder’s outside opening (urethra)
continuously (an indwelling catheter). Intermittent
catheterization should be performed using strict sterile
technique (asepsis) by skilled personnel, and hourly
fluid intake and output must be recorded. Patients
who can use their arms may be taught to catheterize
themselves.
Indwelling catheters avoid distension by emptying
the bladder continuously into a bedside drainage collector. Individuals with indwelling catheters are
encouraged to maintain a high fluid intake in order
to prevent bacteria from accumulating and growing in
the urine. Increased fluid intake also decreases the
concentration of calcium in the urine, minimizing
urine crystallization and the subsequent formation of
stones. Moving around as much as possible and a low
calcium diet also help to reduce stone formation.
Drugs may be used to control the symptoms produced by a neurogenic bladder. The unwanted contractions of an overactive bladder with only small
volumes of urine may be suppressed by drugs that
relax the bladder (anticholinergics) such as propantheline (Pro-Banthine) and oxybutynin (Ditropan).
Contraction of an underactive bladder with normal
bladder volumes may be stimulated with parasympathomimetics (drugs that mimic the action resulting
from stimulation of the parasympathetic nerves) such
as bethanechol (Urecholine).
Long-term management for the individual with an
overactive bladder is aimed at establishing an effective
spontaneous reflex voiding. The amount of fluid taken
in is controlled in measured amounts during the waking hours, with sips only toward bedtime to avoid
bladder distension. At regular intervals during the
day (every four to six hours when fluid intake is two
to three liters per 24 hours), the patient attempts to
void using pressure over the bladder (Crede maneuver). The patient may also stimulate reflex voiding by
abdominal tapping or stretching of the anal sphincter.
The Valsalva maneuver, involving efforts similar to
those used when straining to pass stool, produces an
increase in intra-abdominal pressure that is sometimes
adequate to completely empty the bladder. The
amount of urine remaining in the bladder (residual
GALE ENCYCLOPEDIA OF MEDICINE

For an underactive bladder, the patient may be
placed on a similar bladder routine with fluid intake
and output adjusted to prevent bladder distension. If
an adequate voiding reflex cannot be induced, the
patient may be maintained on clean intermittent
catheterization.
Some individuals who are unable to control urine
output (urinary incontinence) due to deficient sphincter
tone may benefit from perineal exercises. Although
this is a somewhat dated technique, male patients
with extensive sphincter damage may be helped by
the use of a Cunningham clamp. The clamp is applied
in a horizontal fashion behind the glans of the penis
and must be removed approximately every four hours
for bladder emptying to prevent bacteria from growing in the urine and causing an infection. Alternation
of the Cunningham clamp with use of a condom collection device will reduce the skin irritation sometimes
caused by the clamp.
Surgery is another treatment option for incontinence. Urinary diversion away from the bladder may
involve creation of a urostomy or a continent diversion. The surgical implantation of an inflatable
sphincter is another option for certain patients. An
indwelling urinary catheter is sometimes used when
all other methods of incontinence management have
failed. The long-term use of an indwelling catheter
almost inevitably leads to some urinary tract infections, and contributes to the formation of urinary
stones (calculi). Doctors may prescribe antibiotics preventively to reduce recurrent urinary tract infection.

Alternative treatment
The cause of the bladder problem must be determined and treated appropriately. If nerve damage is
not permanent, homeopathy and acupuncture may
help restore function.

KEY TERMS
Anticholinergic—An agent that blocks certain
nerve impulses.
Catheterization—Insertion of a slender, flexible
tube into the bladder to drain urine.
Compliance—A term used to describe how well a
patient’s behavior follows medical advice.
Cystometry—A test of bladder function in which
pressure and volume of fluid in the bladder are
measured during filling, storage, and voiding.
Cystoscopy—A direct method of bladder study and
visualization using a cystoscope (self-contained
optical lens system). The cystoscope can be
manipulated to view the entire bladder, with a
guide system to pass it up into the ureters (tubes
leading from the kidneys to the bladder).
Glans penis—The bulbous tip of the penis.
Motor nerves—Nerves that cause movement when
stimulated.
Parasympathomimetic—An agent whose effects
mimic those resulting from stimulation of the parasympathetic nerves.
Perineal—The diamond-shaped region of the body
between the pubic arch and the anus.
Reflex—An involuntary response to a particular
stimulus.
Sensory nerves—Nerves that convey impulses
from sense organs to the higher parts of the nervous
system, including the brain.
Sphincter—A band of muscles that surrounds a
natural opening in the body; these muscles can
open or close the opening by relaxing or
contracting.
Ureter—A tube leading from one of the kidneys to
the bladder.
Urethra—The tube that leads from the bladder to
the outside of the body.
Urostomy—A diversion of the urinary flow away
from the bladder, resulting in output through the
abdominal wall. The most common method
involves use of a portion of intestine to conduct
the urine out through the abdomen and into an
external pouch worn for urine collection.

Prognosis
Individuals with an overactive bladder caused by
spinal cord lesions at or above the seventh thoracic
vertebra, are at risk for sympathetic dysreflexia, a lifethreatening condition which can occur when the
GALE ENCYCLOPEDIA OF MEDICINE

bladder (and/or rectum) becomes overly full. Initial
symptoms include sweating (particularly on the forehead) and headache, with progression to slow heart
2617

Neurogenic bladder

volume) is estimated by a comparison of fluid intake
and output. The patient also may be catheterized
immediately following the voiding attempt to determine residual urine. Catheterization intervals are
lengthened as the residual urine volume decreases
and catheterization may be discontinued when urine
residuals are at an acceptable level to prevent urinary
tract infection.

Neurolinguistic programming

rate (bradycardia) and high blood pressure (hypertension). Patients should notify their physician promptly
if symptoms do not subside after the bladder (or rectum) is emptied, or if the bladder (or rectum) is full and
cannot be emptied.
Resources
ORGANIZATIONS

Bladder Health Council, American Foundation for Urologic
Disease. 300 West Pratt St., Suite 401, Baltimore, MD
21201. (800) 242-2383 or (410) 727- 2908.
National Association for Continence. P.O. Box 8310,
Spartanburg, SC 29305-8310. (800) 252-3337. <http://
www.nafc.org>.
Simon Foundation for Continence. Box 835, Wilmette, IL
60091.

Kathleen D. Wright, RN

Neuroleptics see Antipsychotic drugs

Neurolinguistic programming
Definition
Neurolinguistic programming (NLP) is aimed at
enhancing the healing process by changing the conscious and subconscious beliefs of patients about
themselves, their illnesses, and the world. These limiting beliefs are ‘‘reprogrammed’’ using a variety of
techniques drawn from other disciplines including
hypnotherapy and psychotherapy.

Purpose
Neurolinguistic programming has been used to
change the limiting beliefs of patients about their prospects of recovery from a wide variety of medical conditions including Parkinson’s disease, AIDS,
migraines, arthritis, and cancer. Practitioners claim
to be able to cure most phobias in less than one hour,
and to help in making lifestyle changes regarding
exercise, diet, smoking, etc. NLP has also been used
to treat allergies. In other fields, claimed benefits
include improved relationships, communication,
motivation, and business performance.

psychology and mathematics student Richard
Bandler, both of the University of California at
Santa Cruz.
Studying the well-known psychotherapist
Virginia Satir, the hypnotherapist Milton Erickson,
the anthropologist Gregory Bateson, and others
whom they considered ‘‘charismatic superstars’’ in
their fields, Grinder and Bandler identified psychological, linguistic and behavioral characteristics that
they said contributed to the greatness of these individuals. On the other hand, they found that persons
experiencing emotional difficulties could be similarly
identified by posture, breathing pattern, choice of
words, voice tone, eye movements, body language,
and other characteristics.
Grinder and Bandler then focused on using these
indicators to analyze and alter patterns of thought and
behavior. After publishing their findings in two books
in 1975, Grinder and Bandler parted company with
themselves, with a number of other collaborators, and
with the University of California, continuing their
work on NLP outside the formal world of academia.
As a result, NLP split into a number of competing
schools.
Popularized by television ‘‘infomercial’’ personality Anthony Robbins and others, NLP was quickly
adopted in management and self-improvement circles.
During the 1990s, there was growing interest in NLP’s
healing potential.
In a health-care context, practitioners of neurolinguistic programming first seek to identify the negative attitudes and beliefs with which a client has been
‘‘programmed’’ since birth. This is accomplished by
asking questions and observing physical responses
such as changes in skin color, muscle tension, etc.
Then, a wide variety of techniques is employed to
‘‘reprogram’’ limiting beliefs. For example, clients
with chronic illness such as AIDS or cancer might be
asked to displace the despair and loss of identity
caused by the disease by visualizing themselves in
vigorous health. Treatment by NLP practitioners is
often of shorter duration than that of other alternative
practitioners, but NLP self-help seminars and courses
can be quite expensive.
For those who wish to try self-treatment with
NLP, a wide variety of books, audio tapes, and videos
are available.

Description
Origins
NLP was originally developed during the early
1970s by linguistics professor John Grinder and
2618

Precautions
NLP is particularly popular in the self-improvement and career-development fields, and some
GALE ENCYCLOPEDIA OF MEDICINE

Because NLP is intended to enhance the healing
process, it should not be used independently of other
healing methods. In all cases of serious illness, a physician should be consulted.

Side effects
NLP is believed to be generally free of harmful
side effects.

Research and general acceptance
Although some physicians and mental health
practitioners employ principles of neurolinguistic programming, the field is generally considered outside of
mainstream medical practice and academic thinking.
Resources
ORGANIZATIONS

Association for NLP. PO Box 78, Stourbridge, UK DY8
2YP.
International NLP Trainers Association, Ltd. Coombe
House, Mill Road, Fareham, Hampshire, UK PO16
0TN. (044) 01489 571171.
Society of Neuro-Lingustic Programming. PO Box 424,
Hopatcong, NJ 07843. (201) 770-3600.

occur unexpectedly suggest a blood vessel or seizure
problem. Those that are not so sudden suggest a possible tumor. Symptoms that have a waning course with
recurrences and worsen over time suggest a disease
that destroys nerve cells. Others that are chronic and
progressive indicate a degenerative disorder. In cases
of trauma, symptoms may be evident upon inspection
and causes may be explained by third party witnesses.
Some patients may require extensive neurological
screening examination (NSE) and/or neurological
examination (NE) to determine the cause. The NH
will assist the clinician to diagnose illnesses such as
seizure disorders, narcolepsy, migraine disorders, dizziness, and dementia.

Description
A neurological screening is an essential component of every comprehensive physical examination. In
cases of neurological trauma, disease, or psychological
disorders patients are usually given a very in-depth
neurological examination. The examination is best
performed in a systematic manner, which means that
there is a recommended order for procedures.
Neurological screening examination
The NSE is basic procedure especially in patients
who have a general neurological complaint or symptoms. The NSE consists of six areas of assessment:

David Helwig

Neurologic bladder dysfunction see
Neurogenic bladder

Neurologic exam
Definition
A neurological examination is an essential component of a comprehensive physical examination. It is
a systematic examination that surveys the functioning
of nerves delivering sensory information to the brain
and caring motor commands (Peripheral nervous system) and impulses back to the brain for processing and
coordinating (Central nervous system).

Purpose
A careful neurological evaluation can help to
determine the cause of impairment since a clinician
can begin localizing the problem. Symptoms that
GALE ENCYCLOPEDIA OF MEDICINE



mental status: assessing normal orientation to time,
place, space, and speech



cranial nerves: checking the eyes with a special light
source (ophthalmoscope), and also assessment of
facial muscles strength and functioning



motor: checking for tone, drift, heal, and toe and
walking



sensory: cold and vibration tests



coordination: observing the patient walk and finger
to nose testing



reflexes: using a special instrument the clinician taps
an area above a nerve to emit a reflex (usually movement of muscle groups)
Neurological examination

The NE should be performed on a patient suspected of having neurological trauma, neurological, or
psychological diseases. The NE is performed in a systematic and comprehensive manner. The NE consists
of several comprehensive and in-depth assessments of
mental status, cranial nerves, motor examination,
2619

Neurologic exam

trainers and practitioners have little experience in its
use for healing. Practitioners should be specifically
asked about this.

Neurologic exam

reflexes, sensory examination, and posture and walking (gait) analysis.
MENTAL STATUS EXAMINATION (MSE). There are
two types of MSE, informal and formal. The informal
MSE is usually done when clinicians are obtaining
historical information from a patient. The formal
MSE is performed in a patient suspected of a neurological problem. The patient is commonly asked his/
her name, the location, the day, and date. Retentive
memory capability and immediate recall can be
assessed by determining the number of digits that can
be repeated in sequence. Recent memory is typically
examined by testing recall potential of a series of
objects after defined times, usually within five and 15
minutes. Remote memory can be assessed by asking
the patient to review in a coherent and chronological
fashion, his or her illness or personal life events that
the patient feels comfortable talking about. Patient
recall of common historical or current events can be
utilized to assess general knowledge. Higher functioning (referring to brain processing capabilities) can be
assessed by spontaneous speech, repetition, reading,
naming, writing, and comprehension. The patient may
be asked to perform further tasks such as identification of fingers, whistling, saluting, brushing teeth
motions, combing hair, drawing, and tracing figures.
These procedures will assess the intactness of what is
called dominant (left-sided brain) functioning or
higher cortical function referring to the portion of
the brain that regulates these activities.

The MSE is particularly important in the specialty
of psychotherapy. Psychotherapists recommend an indepth MSE to all patients with possible organic (referring to the body) or psychotic disorders. This examination is also performed in a systematic and orderly
manner. It is divided into several categories:




Appearance: This assessment determines the
patient’s presentation, i.e., how the patient looks
(clothes posture, grooming, and alertness).
Behavior: This assesses the patient’s motor (movements) activity such as walking, gestures, muscular
twitching, and impulse control.



Speech: the patient’s speech can be examined concerning volume, rate of speech and coherence.
Patients who exhibit latent or delayed speech can
indicate depression, while a rapid or pressured
speech may suggest possible mania or anxiety.



Mood and affect: Normal mood is term euthymia.
There is variation in mood presentations and
patients may display a flat, labile, blunted, constructed or inappropriate mood. The patient can

2620

also be euphoric (elevated) or dysphoric (on the
down side).


Thought processes and content: This category is
typically assessed by determining word usage (can
indicate brain disease), thought stream (whether
thoughts are slow, restricted, blocked, or overabundant), continuity of thought (referring to associations among ideas), and content of thought
(delusional thoughts).



Perception: This assessment examines the patient’s
ability to hear, see, touch, taste, and smell. Certain
psychological states may cause hearing and visual
hallucinations. Impairments of smell and touch are
usually caused by medical (organic) causes or as side
effects from certain medications.



Attention and concentration: This clinician assesses
the patient’s ability to focus on a specific task or
activity. Abnormalities in attention and concentration can indicate problems related to anxiety or
hallucinations.



Orientation: The patient is examined for orientation
to time, place, and identification of self (asking the
patient his/her name). Disturbances in orientation
can be due to a medical condition (other than psychological), substance abuse, or as a side effect of
certain medications such as those used to treat
depression, anxiety or psychosis (since these medications usually have a sedative affect).



Memory: Patients are examined for remote, recent,
and immediate memory capabilities. Remote and
recent memory can be assessed by the patient’s ability to recall historical and current events. Immediate
memory can be tested by naming three objects and
asking the patient to repeat the named objects immediately, then after five and 15 minute intervals.



Judgment: This category evaluates the patient’s ability to exercise appropriate judgment. It also determines whether the patient has an understanding of
consequences associated with their actions.



Intelligence and information: The only precise measurement for this category can be obtained by administering specialized intelligence tests, However a
preliminary assessment of intelligence can be made
based on the patient’s fund of information, general
knowledge, awareness of current events, and the
ability for abstract thinking (thinking of unique
concepts).



Insight: Insight in the MSE pertains to the patient’s
awareness of their problem that prompted them to
seek professional examination. Insight concerning
GALE ENCYCLOPEDIA OF MEDICINE

CRANIAL NERVES (CN). Cranial nerves are specialized nerves that originate in the brain and connect to
specialized structures such as the nose, eyes, muscles in
the face, scalp, ear, and tongue.


CNI: This nerve checks for visual capabilities.
Patients are usually given the Snellen Chart (a chart
with rows of large and small letters). Patients read
letters with one eye at a time.



CN III, IV, and VI: These nerves examine the pupillary (the circular center structure of the eye that light
rays enter) reaction. The pupils get smaller, normally
when exposed to the light. The eyelids are also examined for drooping or retraction. The eyeball is also
checked for abnormalities in movement.



CNV: The clinician can assess the muscles on both
sides of the scalp muscles (the temporalis muscle).
Additionally the jaw can be tested for motion resistance, opening, protrusion, and side-to-side mobility. The cornea located is a transparent tissue
covering the eyeball and could be tested for intactness by lightly brushing a wisp of cotton directly on
the outside of the eye.



CNVII: Examination of CNVII assesses asymmetry
of the face at rest and during spontaneous movements. The patient is asked to raise eyebrows, wrinkle forehead, close eyes, frown, smile, puff cheeks,
purse lips, whistle, and contract chin muscles. Taste
for the front and middle portions of the tongue can
also be examined.



CNVIII: Testing for this CN deals with hearing. The
clinician usually uses a special instrument called a
tuning fork and tests for air conduction and structural problems which can occur inside the ear.



CN IX and X: These tests will evaluate certain structures in the mouth. The clinician will usually ask the
patient to say ‘‘aah’’ and can detect abnormal positioning of certain structures such as the palatel-uvula.
The examiner will also assess the sensation capabilities
of the pharynx, by stimulating the area with a wooden
tongue depressor, causing a gag reflex.



CNXI: This nerve is usually examined by asking the
patient to shrug shoulders (testing a muscle called the
trapezius) and rotating the head to each side (testing
a muscle called the sternocleidomastoid). These muscles are responsible for movement of the shoulders
and neck. The test is usually done with resistance,
meaning the examiner holds the area while the
patient is asked to move. This is done to assess
patient’s strength in these areas.

GALE ENCYCLOPEDIA OF MEDICINE



CNXII: This nerve tests the bulk and power of the
tongue. The examiner looks for tongue protrusion
and/or abnormal movements.

MOTOR EXAMINATION. The motor examination
assesses the patient’s muscle strength, tone, and
shape. Muscles could be abnormally larger than
expected (hypertrophy) or small due to tissues destruction (atrophy). It is important to assess if there is
evidence of twitching or abnormal movements.
Involuntary movements due to tics or myoclonus can
be observed. Additionally, movements can be abnormal during maintained posture in neurological disorders such as Parkinson’s disease. Muscle tone is
usually tested by applying resistance to passive motion
of a relaxed limb. Power is assessed for movements at
each joint. Decreases or increases in muscle tone can
help the examiner localize the affected area.
REFLEXES. The patient’s reflexes are tested by using
a special instrument that looks like a little hammer.
The clinician will tap the rubber triangular shaped end
in several different areas in the arms, knee, and
Achilles heal area. The clinician will ask the patient
to relax and gently tap the area. If there is a difference
in response from the left to right knee, then there may
be an underlying problem that merits further evaluation. A difference in reflexes between the arms and legs
usually indicates of a lesion involving the spinal cord.
Depressed reflexes in only one limb, while the other
limb demonstrates a normal response usually indicates
a peripheral nerve lesion.
SENSORY EXAMINATION. Although a very essential
component of the NE, the sensory examination is the
least informative and least exacting since it requires
patient concentration and cooperation. Five primary
sensory categories are assessed: vibration (using a tuning fork), joint position (examiner moves the limb
side-to-side and in a downward position), light
touch, pinprick, and temperature. Patients who have
sensory abnormalities may have a lesion above the
thalamus. Spinal cord lesions or disease can possibly
be detected by pinprick and temperature assessment.
COORDINATION. The patient is asked to repetitively touch his nose using his index finger and then
to touch the clinician’s outstretched finger.
Coordination can also be assessed by asking the
patient to alternate tapping the palm then the back
of one hand on the thigh. For coordination in the
lower extremities on legs, the patient lies on his or
her back and is asked to slide the heel of each foot
from the knee down the shin of the opposite leg and to
raise the leg and touch the examiners index finger with
the great toe.

2621

Neurologic exam

the present illness can range from denial to fleeting
admission of current illness.

Neutropenia

KEY TERMS
Corticospinal tract—A tract of nerve cells that carries motor commands from the brain to the spinal
cord.
Gait—Referring to walking motions.
Reflex—A response, usually a movement, elicited
by tapping on the nerve with a special hammer-like
instrument.
Thalamus—A part of the brain that filters incoming
sensory information.

WALKING (GAIT). Normal walking is a complex
process and requires usage of multiple systems such as
power, coordination and sensation working together in
a coordinated fashion. The examination of gait can
detect a variety of disease states. Decreased arm swinging on one side is indicative of corticospinal tract disease.
A stooped down posture and short-stepped gait may
suggest Parkinson’s syndrome. A high stepped, slapping
gait may be the result of a peripheral nerve disease.

an acute insult such as stroke or trauma, the patient is
usually admitted to the hospital for appropriate treatment. Some neurological diseases are chronic and
require conservative (medical) treatment and frequent
follow-up visits for monitoring and stability or progression of the disease state. The MSE and NE are
good diagnostic tools. Further testing using advanced
technological procedures is usually required for definitive diagnosis and initiation of disease-specific
treatment.
The outcome depends ultimately on the final diagnosis. Neurological diseases typically follow a chronic
course. Situations that present as trauma may require
surgical intervention and intensive care with an outcome usually proportional to extent of injuries.
Psychological disorders may require long term
(chronic) treatment and/or medication(s). Most neurological conditions require follow-up and periodic
monitoring.
Resources
BOOKS

Behrman, Richard E., et al, editors. Nelson Textbook of
Pediatrics. 16th ed. W. B. Saunders Company, 2000.
Goldman, Lee, et al. Cecil’s Textbook of Medicine. 21st ed.
W. B. Saunders Company, 2000.

Preparation
The MSE is the first step in a continuous assessment to determine the diagnosis a psychotherapist
should take a detailed medical history in the process
of ruling out a general medical condition. If a general
medical disease is suspected, referral is indicated to rule
out this category. Once a medical condition has been
fully excluded the therapist can then localize the components of an abnormal MSE to determine the underlying psychological disorder. Once this is determined
treatment may include, but is not limited to therapy
sessions and/or medication. For neurological diseases
the clinician will use information gained from the NE
for ordering further tests. These tests may include a
complete blood analysis, liver function tests, kidney
function tests, hormone tests, and a lumbar puncture
to determine abnormalities in cerebrospinal fluid. In
cases of trauma (car accident, sports injury) the NE is
a quick and essential component of emergency assessment. One a diagnosis is determined emergency measures may include further tests and/or surgery.

Aftercare
Care is usually specific once the final diagnosis has
been determined. In psychological cases the treatment
may include therapy and/or medication. In causes of
2622

Laith Farid Gulli, M.D.
Bilal Nasser, M.Sc.

Neuromuscular junction disease see
Myasthenia gravis
Neuropathic bladder see Neurogenic
bladder

Neutropenia
Definition
Neutropenia is an abnormally low level of neutrophils in the blood. Neutrophils are white blood cells
(WBCs) produced in the bone marrow that ingest
bacteria. Neutropenia is sometimes called agranulocytosis or granulocytopenia because neutrophils make
up about 60% of WBCs and have granules inside their
cell walls. Neutropenia is a serious disorder because it
makes the body vulnerable to bacterial and fungal
infections.
GALE ENCYCLOPEDIA OF MEDICINE

The normal level of neutrophils in human blood
varies slightly by age and race. Infants have lower
counts than older children and adults, and African
Americans have lower counts than Caucasians or
Asians. The average adult level is 1500 cells/mm3 of
blood. Neutrophil counts (in cells/mm3) are interpreted as follows:


greater than 1000. Normal protection against
infection



500–1000. Some increased risk of infection



200–500. Great risk of severe infection



lower than 200. Risk of overwhelming infection;
requires hospital treatment with antibiotics

Causes and symptoms
Causes
Neutropenia may result from three processes:
DECREASED WBC PRODUCTION. Lowered production of white blood cells is the most common cause of
neutropenia. It can result from:



felty’s syndrome or malaria, the neutrophils accumulate in the spleen



bacterial infections, the neutrophils remain in the
infected tissues without returning to the bloodstream
Symptoms

Neutropenia has no specific symptoms except the
severity of the patient’s current infection. In severe
neutropenia, the patient is likely to develop periodontal disease, oral and rectal ulcers, fever, and bacterial pneumonia. Fever recurring every 19–30 days
suggests cyclical neutropenia.

Diagnosis
Diagnosis is made on the basis of a white blood
cell count and differential. The cause of neutropenia is
often difficult to establish and depends on a combination of the patient’s history, genetic evaluation, bone
marrow biopsy, and repeated measurements of the
WBC.

Treatment

medications that affect the bone marrow, including
cancer drugs, chloramphenicol (Chloromycetin),
anticonvulsant medications, and antipsychotic drugs
(Thorazine, Prolixin, and other phenothiazines)

Treatment of neutropenia depends on the underlying cause.



hereditary and congenital disorders that affect the
bone marrow, including familial neutropenia, cyclic
neutropenia, and infantile agranulocytosis



cancer, including certain types of leukemia



radiation therapy

Patients with fever and other signs of infection are
treated for seven to 10 days with antibiotics.
Nutritional deficiencies are corrected by green vegetables to supply folic acid, and by vitamin B
supplements.



exposure to pesticides



vitamin B12 and folate (folic acid) deficiency



DESTRUCTION OF WBCS. WBCs are used up at a

faster rate by:


acute bacterial infections in adults



infections in newborns



certain autoimmune disorders, including systemic
lupus erythematosus (SLE)



penicillin, phenytoin (Dilantin), and sulfonamide
medications (Benemid, Bactrim, Gantanol)

SEQUESTRATION
AND
MARGINATION
OF
WBCS. Sequestration and margination are processes

in which neutrophils are removed from the general
blood circulation and redistributed within the body.
These processes can occur because of:


hemodialysis

GALE ENCYCLOPEDIA OF MEDICINE

Medications

Medications known to cause neutropenia are
stopped. Neutropenia related to pesticide exposure is
treated by removing the patient from the contaminated environment.
Patients receiving chemotherapy for cancer may be
given a blood growth factor called sargramostim
(Leukine, Prokine) to stimulate WBC production.
Surgery
Patients with Felty’s syndrome who have repeated
infections may have their spleens removed.

Prognosis
The prognosis for mild or chronic neutropenia is
excellent. Recovery from acute neutropenia depends
on the severity of the patient’s infection and the
promptness of treatment.
2623

Neutropenia

Description

Night terrors

Nifedipine see Calcium channel blockers

KEY TERMS
Cyclical neutropenia—A rare genetic blood disorder in which the patient’s neutrophil level drops
below 500/mm3 for six to eight days every three
weeks.
Differential—A blood cell count in which the percentages of cell types are calculated as well as the
total number of cells.
Felty’s syndrome—An autoimmune disorder in
which neutropenia is associated with rheumatoid
arthritis and an enlarged spleen.
Granulocyte—Any of several types of white blood
cells that have granules in their cell substance.
Neutrophils are the most common type of
granulocyte.
Neutrophil—A granular white blood cell that
ingests bacteria, dead tissue cells, and foreign
matter.
Sargramostim—A medication made from yeast that
stimulates WBC production. It is sold under the
trade names Leukine and Prokine.
Sequestration and margination—The removal of
neutrophils from circulating blood by cell changes
that trap them in the lungs and spleen.

Night blindness see Vitamin A deficiency

Night terrors
Definition
Night terrors are a sleep disorder characterized by
anxiety episodes with extreme panic, often accompanied by screaming, flailing, fast breathing, and sweating and that usually occur within a few hours after
going to sleep.

Description
Night terrors occur most commonly in children
between the ages of four and 12 but can also occur at
all ages. Affected individuals usually suffer these episodes within a few hours after going to sleep. They
appear to bolt up suddenly, and wake up screaming,
sweating and panicked. The episode may last anywhere from five to 20 minutes. During this time, the
individual is actually asleep, although the eyes may
open. Quite often, nothing can be done to comfort the
affected person. Very often, the person has no memory
of the episode upon waking the next day.
Night terrors are differentiated from nightmares
in that they have been shown to occur during Stage 4
of sleep, or in REM sleep, while nightmares can occur
anytime throughout the sleep cycle.

Resources
BOOKS

Linker, Charles A. ‘‘Blood.’’ In Current Medical
Diagnosisand Treatment, 1998, edited by Stephen
McPhee, et al., 37th ed. Stamford: Appleton &Lange,
1997.

Rebecca J. Frey, PhD

Nevirapine see Non-nucleoside reverse
transcriptase inhibitors
Nevus see Moles

Causes and symptoms
Suffering from night terrors seems to run in
families. Extreme tension or stress can increase the
incidence of the episodes. In adults, the use of alcohol
also contributes to an increased incidence of night
terrors. Episodes sometimes occur after an accident
involving head injury. Other factors thought to contribute to episodic night terrors, but not actually cause
them, include:

Newborn life support see Extracorporeal
membrane oxygenation



medications



excessive tiredness at bedtime

Niacin deficiency see Pellagra



eating a heavy meal prior to bedtime

Nicotine see Smoking; Smoking-cessation
drugs
Nicotinic acid deficiency see Pellagra
Niemann-Pick disease see Lipidoses
2624

drug abuse
Diagnosis
Night terrors are primarily diagnosed by observing the person suffering from an episode. The
GALE ENCYCLOPEDIA OF MEDICINE



panic



sweating



gasping, moaning, crying or screaming during sleep



little or no recollection of the episode upon
awakening

Treatment
In most cases, the individual will still be asleep as
the night terror episode happens and will prove difficult to awaken. The goal should be to help the affected
person go back into a calm state of sleep. The lights
should be turned on, and soothing comments should
be directed at the person, avoiding brusque gestures
such as shaking the person or shouting to startle them
out of the episode. Any form of stress should be
avoided.
Individuals affected by night terrors should be
evaluated by a physician if they are really severe and
occur frequently. A physician can recommend the best
treatment for the particular circumstances of the night
terrors. In some severe cases, the physician may prescribe a benzodiazepine tranquilizer, such as Diazepam,
known to suppress Stage 4 of sleep. The physician may
also refer the affected person for further evaluation by a
sleep disorder specialist. It should be noted that episodic night terrors in children are normal and do not
suggest the presence of psychological problems. In
adults, night terrors are more likely to be related to a
significant stress-related or emotional problem.

KEY TERMS
Benzodiazepines—A class of drugs that suppresses
Stage 4 of sleep.
REM sleep—Rapid Eye Movement phase of sleep, a
mentally active period during which dreaming
occurs.
Sleep disorder—Any disorder that keep a person
from falling asleep or staying asleep.

Resources
PERIODICALS

American Academy of Family Physicians. ‘‘Nightmares and
Night Terrors in Children.’’ October 2000.
Laberge, Luc, et al. ‘‘Development of Parasomnias from
Childhood to Early Adolescence.’’ Pediatrics July 2000:
67-74.
ORGANIZATIONS

American Sleep Disorders Association, 6301 Bandel Road
Suite 101, Rochester, MN 55901. (507) 287-6008.
<http://www.asda.org>.
National Foundation for Sleep and Related Disorders in
Children. 4200 W. Peterson Suite 109, Chicago, IL
60646. (708) 971-1086.

Kim A. Sharp, M.Ln.

Nitrates see Antiangina drugs
Nitrofurantoin see Urinary anti-infectives

Prognosis
In children, night terror episodes in children
usually end by the age of 12.

Nitrogen narcosis
Definition

Prevention
If a child seems to have a regular pattern of night
terror episodes, he should be gently awakened about
15 minutes before the episode usually happens. The
child should be kept awake and out of the bed for a
short period of time and then allowed to return to bed.
Since sleep deprivation is a strong trigger for night
terror episodes, children should not be allowed to
become overtired. Having children take a nap during
the day may be useful.
Adults affected by night terror episodes should
avoid stress, the consumption of alcohol and stimulants before going to sleep.
GALE ENCYCLOPEDIA OF MEDICINE

Nitrogen narcosis is a condition that occurs in
divers breathing compressed air. When divers go
below depths of approximately 100 ft, increase in the
partial pressure of nitrogen produces an altered mental state similar to alcohol intoxication.

Description
Nitrogen narcosis, commonly referred to as ‘‘rapture of the deep,’’ typically becomes noticeable at
100 ft underwater and is incapacitating at 300 ft, causing
stupor, blindness, unconsciousness, and even death.
Nitrogen narcosis is also called ‘‘the martini effect’’
because divers experience an effect comparable to that
2625

Nitrogen narcosis

following symptoms are characteristic of a person
suffering from a night terror:

Nitrogen narcosis

from one martini on an empty stomach for every 50 ft of
depth beyond the initial 100 ft.

Causes and symptoms
Nitrogen narcosis is caused by gases in the body
acting in a manner described by Dalton’s Law of
partial pressures: the total pressure of a gas mixture
is equal to the sum of the partial pressures of gases in
the mixture. As the total gas pressure increases with
increasing dive depth, the partial pressure of nitrogen
increases and more nitrogen becomes dissolved in the
blood. This high nitrogen concentration impairs the
conduction of nerve impulses and mimics the effects of
alcohol or narcotics.
Symptoms of nitrogen narcosis include: wooziness; giddiness; euphoria; disorientation; loss of balance; loss of manual dexterity; slowing of reaction
time; fixation of ideas; and impairment of complex
reasoning. These effects are exacerbated by cold,
stress, and a rapid rate of compression.

Diagnosis
A diagnosis must be made on circumstantial evidence of atypical behavior, taking into consideration
the depth of the dive and the rate of compression.
Nitrogen narcosis may be differentiated from toxicity
of oxygen, carbon monoxide, or carbon dioxide by the
absence of such symptoms as headache, seizure, and
bluish color of the lips and nail beds.

Treatment
The effects of nitrogen narcosis are totally reversed
as the gas pressure decreases. They are typically gone by
the time the diver returns to a water depth of 60 ft.
Nitrogen narcosis has no hangover or lasting effects
requiring further treatment. However, a doctor should
be consulted whenever a diver has lost consciousness.

Prognosis
When a diver returns to a safe depth, the effects of
nitrogen narcosis disappear completely. Some evidence exists that certain divers may become partially
acclimated to the effects of nitrogen narcosis with
frequency—the more often they dive, the less the
increased nitrogen seems to affect them.

Prevention
Helium may be used as a substitute for nitrogen to
dilute oxygen for deep water diving. It is colorless,
2626

KEY TERMS
Compressed air—Air that is held under pressure in
a tank to be breathed by underwater divers. A tank
of compressed air is part of a diver’s scuba (selfcontained underwater breathing apparatus) gear.
Compression—An increase in pressure from the
surrounding water that occurs with increasing diving depth.
Partial pressure—The pressure exerted by one of
the gases in a mixture of gases. The partial pressure
of the gas is proportional to its concentration in the
mixture. The total pressure of the gas mixture is the
sum of the partial pressures of the gases in it
(Dalton’s Law) and as the total pressure increases,
each partial pressure increases proportionally.

odorless, tasteless, and chemically inert. However, it
is more expensive than nitrogen and drains body heat
from a diver. In diving with rapid compression, the
helium-oxygen mixture may produce nausea, dizziness, and trembling, but these adverse reactions are
less severe than nitrogen narcosis.
Nitrogen narcosis can be avoided by limiting the
depth of dives. The risk of nitrogen narcosis may also
be minimized by following safe diving practices,
including proper equipment maintenance, low work
effort, proper buoyancy, maintenance of visual cues,
and focused thinking. In addition, no alcohol should
be consumed within 24 hours of diving.
Resources
ORGANIZATIONS

American College of Hyperbaric Medicine. P.O. Box
25914-130, Houston, Texas 77265. (713) 528-0657.
<http://www.hyperbaricmedicine.org>.
Divers Alert Network. The Peter B. Bennett Center, 6 West
Colony Place, Durham, NC 27705. (800) 446-2671.
<http://www.diversalertnetwork.org>.
Undersea and Hyperbaric Medical Society. 10531
Metropolitan Ave., Kensington, MD 20895. (301)
942-2980. <http://www.uhms.org>.

Bethany Thivierge

Nitroglycerin see Antiangina drugs
Nlein purpura see Allergic purpura
NMR see Magnetic resonance imaging
GALE ENCYCLOPEDIA OF MEDICINE

Nocardiosis
Definition
Nocardiosis is a serious infection caused by a
fungus-like bacterium that begins in the lungs and
can spread to the brain.

Description
Nocardiosis is found throughout the world
among people of all ages, although it is most common
in older people and males. While people with poor
immunity are vulnerable to this infection, it sometimes
strikes individuals with no history of other diseases.
Nocardiosis is rare in AIDS patients. It is not transmitted by person-to-person contact.

Causes and symptoms
Nocardiosis is caused by a bacterium of the
Nocardia species—usually N. asteroides, an organism
that is normally found in the soil. The incubation
period is not known, but is probably several weeks.
The bacteria can enter the human body when a
person inhales contaminated dust. Less often, people
can pick up the bacteria in contaminated puncture
wounds or cuts.

KEY TERMS
Abscess—A localized area of infection in a body
tissue. Abscesses in the brain or skin are possible
complications of nocardiosis.
Meningitis—An infection of the outer covering of
the brain (meninges) that can be caused by either
bacteria or a virus.

skin. They may also have lesions in other organs, such
as the kidneys, liver, or bones.

Diagnosis
Nocardia is not easily identified from cultures of
sputum or discharge. A doctor can diagnose the condition using special staining techniques and taking a
thorough medical history. Lung biopsies or x rays also
may be required. Up to 40% of the time, however, a
diagnosis can’t be made until an autopsy is done.

Treatment
Treatment of nocardiosis includes bed rest and
high doses of medication for a period of 12 to 18
months, including sulfonamide drugs or a combination of trimethoprim-sulfamethoxazole (Bactrim,
Septra). If the patient doesn’t respond to these drugs,
antibiotics such as ampicillin (Amcill, Principen) or
erythromycin (E-Mycin, Eryc) may be tried.
The abscesses may need to be drained and dead
tissue cut away. Other symptoms are treated as
necessary.

Symptoms
The infection causes a cough similar to pneumonia or
tuberculosis, producing thick, sometimes bloody, sputum. Other symptoms include chills, night sweats, chest
pain, weakness, loss of appetite and weight loss.
Nocardiosis does not, however, respond to short-term
antibiotics.
Complications
In about one-third of patients, the infection spreads
from the blood into the brain, causing brain abscesses.
This complication can trigger a range of symptoms
including severe headache, confusion, disorientation,
dizziness, nausea and seizures, and problems in walking.
If a brain abscess ruptures, it can lead to meningitis.
About a third of patients with nocardiosis also
have abscesses in the skin or directly underneath the
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Nocardiosis is a serious disease with a high mortality rate. If it has been diagnosed early and caught before
spreading to the brain, the prognosis is better. Even
with appropriate treatment, however, the death rate is
still 50%. Once the infection reaches the brain, the death
rate is above 80%. This outcome is most commonly
seen in patients with a weakened immune system.
Resources
BOOKS

Orris, June, editor. Handbook of Diseases. Springhouse, PA:
Springhouse Corp., 1996.

Carol A. Turkington

Nodule see Skin lesions
2627

Nocardiosis

Nocardia asteroides infection see
Nocardiosis

Nongonococcal urethritis

Non-Hodgkin’s lymphomas see Malignant
lymphomas

KEY TERMS

Non-melanoma skin cancer see Skin cancer,
non-melanoma

Human immunodeficiency virus (HIV)—The virus
that causes AIDS.

Non-nucleoside reverse
transcriptase inhibitors
Definition
This type of drug interferes with an enzyme that is
key to the replication (reproduction) of the human
immunodeficiency virus (HIV). The drug is designed
to help suppress the growth of HIV, but does not
eliminate it.

Purpose
This medication is used to treat patients with the
HIV virus and AIDS in combination with one or more
other AIDS drugs. Combining NRTIs with older drugs
improves their ability to lower the levels of HIV in the
bloodstream, and strengthens the immune system.
HIV becomes rapidly resistant to this class of drugs
when they are used alone. However, in combination
with older drugs, they can interfere with the virus’s
ability to become resistant because they attack the
virus on several fronts. As the virus tries to evade one
drug, another attacks. This combination can lower the
level of HIV in the blood to undetectable levels.

Precautions
Patients should not discontinue this drug even if
symptoms improve without consultation with a
physician.

Depending on the drug prescribed, doses may
start with a lower amount and be increased after a
short period of time.

Risks
A mild skin rash is common; a severe skin rash can
be a life threatening reaction. Other possible side effects
include fever, blistering skin, mouth sores, aching joints,
eye inflammation, headache, nausea, and tiredness.
Because the drug passes into breast milk, breastfeeding mothers should avoid the drug, or not nurse
until the treatment is completed.
Resources
ORGANIZATIONS

National AIDS Treatment Advocacy Project. 580
Broadway, Ste. 403, New York, NY 10012. (888)
266-2827. <http://www.natap.org>.

Carol A. Turkington

Non-small cell lung cancer see Lung cancer,
non-small cell
Non-A, non-B hepatitis see Hepatitis C
Non-tuberculous see Mycobacterial
infections, atypical
Nonbacterial regional lymphaden see
Cat-scratch disease
Noncholera vibrio infections see Vibriosis

Description
Nucleoside analogues, the first class of HIV drugs
to be developed, worked by incorporating themselves
into the virus’s DNA, making the DNA incomplete
and therefore unable to create a new virus. Nonnucleoside inhibitors work at the same stage as nucleoside analogues, but act in a completely different way,
preventing the conversion of RNA to DNA.
This class of drugs includes nevirapine (Viramune)
and delavirdine (Rescriptor). It may take several weeks
or months before the full benefits are apparent.
2628

Noneros see Gastritis

Nongonococcal urethritis
Definition
Any inflammation of the urethra not due to
gonorrhea, almost always contracted through sexual
intercourse and found far more often in men.
GALE ENCYCLOPEDIA OF MEDICINE

Nongonococcal urethritis

Description
Men between the ages of 15 and 30 who have
multiple sex partners are most at risk for nongonococcal urethritis (NGU), which is believed to be the most
common sexually transmitted disease in the United
States.

Causes and symptoms
NGU is spread almost exclusively via sexual
contact, and appears most often in men because a
woman’s urethra is less easily infected during sex.
The infection is most often due to Chlamydia trachomatis, the organism that causes chlamydia. Those
that aren’t caused by Chlamydia trachomatis are
usually due to another bacterium, Ureaplasma urealyticum. In 10% to 20% of NGU cases, the cause is
unknown.
Symptoms appear within one to five weeks after
infection, and include a slight clear discharge (the
color of the discharge can vary from one patient to
the next), and itching or burning during or after
urination.
However, some men never develop symptoms,
and women almost never show signs of infection.
However, it’s possible that symptoms of burning or
itching in or around the vagina may be due to NGU.
The disease is communicable from the time of first
infection until the patient is cured. Past infection
doesn’t make a person immune.

A microscopic image of non-specific urethritis. This sexually
transmitted disease is usually caused by a bacterium of the
genus Chlamydia. (Custom Medical Stock Photo. Reproduced
by permission.)

KEY TERMS
Chlamydia—One of the most common sexually
transmitted diseases in the United States. It causes
discharge, inflammation and burning during urination. About half of the cases of nongonococcal
urethritis are due to chlamydia.
Gonorrhea—A sexually transmitted disease that
affects the genital mucous membranes of men and
women.
Urethra—The tube that carries urine from the bladder through the outside of the body.

Diagnosis
Nongonococcal urethritis is diagnosed by excluding other causes, since inflammation that is not caused
by gonorrhea is classified as NGU. A microscopic and/
or culture test of the discharge or urine can reveal the
infection.
Since many people are infected with both NGU
and syphilis at the same time, infected patients also
should have a test for syphilis before treatment for
NGU begins, and three months after treatment ends.

Treatment
Antibiotics such as tetracycline or azithromycin
will cure NGU; both sexual partners should be treated
at the same time.
Patients taking tetracycline should avoid milk or
milk products and take the medication at least one
hour before or two hours after meals. On the last day
of treatment, a male should have a urine test to make
GALE ENCYCLOPEDIA OF MEDICINE

sure the infection has cleared. If it hasn’t, he should
take a second course of therapy. Men should use a
condom during treatment and for several months after
treatment is completed.
If urine tests indicate the infection is gone but
symptoms persist, the doctor will check for signs of
prostate inflammation.

Prognosis
NGU is completely curable with proper antibiotic
treatment. Untreated, NGU can lead to sterility in
both men and women, inflammation of the mouth of
the uterus, and infections of the woman’s internal
sexual organs. An infection during pregnancy may
lead to pneumonia or eye infections in the newborn
child. Untreated men may develop swelling of the
testicles and an infected prostate gland.
2629

Nonsteroidal anti-inflammatory drugs

Prevention
People can prevent the spread of NGU by:


using a condom



limiting the number of sex partners



washing the genital area after sex



if infected, avoid sexual contact; take antibiotics,
notify all partners

Resources
ORGANIZATIONS

American Social Health Association. P.O. Box 13827,
Research Triangle Park, NC 27709. (800) 227-8922.
<http://www.ashastd.org>.
OTHER

Sexually Transmitted Diseases Hotline. (800) 227-8922.

Carol A. Turkington

Nonsteroidal antiinflammatory drugs
Definition
Nonsteroidal anti-inflammatory drugs are medicines that relieve pain, swelling, stiffness, and
inflammation.

Purpose
Nonsteroidal anti-inflammatory drugs (NSAIDs)
are prescribed for a variety of painful conditions,
including arthritis, bursitis, tendinitis, gout, menstrual
cramps, sprains, strains, and other injuries. They are
also given to control the pain of cancer and the side
effects of radiation therapy.
A group of researchers associated with the
Women’s Health Initiative reported in 2003 that regular use of aspirin, ibuprofen, and other NSAIDs may
help to lower a woman’s risk of developing breast
cancer. Further clinical trials are needed, however, to
confirm the group’s findings.

Description
Nonsteroidal anti-inflammatory drugs relieve pain,
stiffness, swelling, and inflammation, but they do not cure
the diseases or injuries responsible for these problems.
Two drugs in this category, ibuprofen and naproxen, also
2630

reduce fever. Some nonsteroidal anti-inflammatory drugs
can be bought over the counter; others are available only
with a prescription from a physician or dentist.
Among the drugs in this group are diclofenac
(Voltaren), etodolac (Lodine), flurbiprofen (Ansaid),
ibuprofen (Motrin, Advil, Rufen), ketorolac (Toradol),
nabumetone (Relafen), naproxen (Naprosyn); naproxen
sodium (Aleve, Anaprox, Naprelan); and oxaprozin
(Daypro). They are sold as tablets, capsules, caplets,
liquids, and rectal suppositories and some are available
in chewable, extended-release, or delayed-release forms.
A newer group of NSAIDs known as COX-2
inhibitors are being used successfully to treat patients
with allergic reactions to the older NSAIDs. Their
name comes from the fact that they block an enzyme
known as cyclooxygenase-2, or COX-2, which is
involved in the inflammation pathway. The COX-2
inhibitors are also less likely to affect the patient’s
digestive tract. They include such drugs as celecoxib
(Celebrex), rofecoxib (Vioxx), etoricoxib (Arcoxia),
and valdecoxib (Bextra). With regard to cancer treatment, some studies indicate that the use of COX-2
inhibitors may postpone the need to prescribe narcotic
medications for severe pain.

Recommended dosage
Recommended doses vary, depending on the
patient, the type of nonsteroidal anti-inflammatory
drug prescribed, the condition for which the drug is
prescribed, and the form in which it is used. Always
take nonsteroidal anti-inflammatory drugs exactly as
directed. If using non-prescription (over-the-counter)
types, follow the directions on the package label. For
prescription types, check with the physician who prescribed the medicine or the pharmacist who filled the
prescription. Never take larger or more frequent
doses, and do not take the drug for longer than directed. Patients who take nonsteroidal anti-inflammatory
drugs for severe arthritis must take them regularly
over a long time. Several weeks may be needed to feel
the results, so it is important to keep taking the medicine, even if it does not seem to be working at first.
When taking nonsteroidal anti-inflammatory
drugs in tablet, capsule, or caplet form, always take
them with a full, 8-ounce glass of water or milk.
Taking these drugs with food or an antacid will help
prevent stomach irritation.

Precautions
Nonsteroidal anti-inflammatory drugs can cause
a number of side effects, some of which may be very
GALE ENCYCLOPEDIA OF MEDICINE

Do not take acetaminophen, aspirin, or other salicylates along with other nonsteroidal anti-inflammatory drugs for more than a few days unless directed to
do so by a physician. Do not take ketorolac (Toradol)
while taking other nonsteroidal anti-inflammatory
drugs unless directed to do so by a physician.
Because older people are more sensitive than
younger adults to nonsteroidal anti-inflammatory
drugs, they may be more likely to have side effects.
Some side effects, such as stomach problems, may also
be more serious in older people.
Serious side effects are especially likely with one
nonsteroidal anti-inflammatory drug, phenylbutazone. Patients age 40 and over are especially at risk
of side effects from this drug, and the likelihood of
serious side effects increases with age. Because of these
potential problems, it is especially important to check
with a physician before taking this medicine. Never
take it for anything other than the condition for which
it was prescribed, and never share it—or any other
prescription drug—with another person.
Some nonsteroidal anti-inflammatory drugs can
increase the chance of bleeding after surgery (including dental surgery), so anyone who is taking the drugs
should alert the physician or dentist before surgery.
Avoiding the medicine or switching to another type in
the days prior to surgery may be necessary.
Some people feel drowsy, dizzy, confused, lightheaded, or less alert when using these drugs. Blurred
vision or other vision problems also are possible side
effects. For these reasons, anyone who takes these
drugs should not drive, use machines or do anything
else that might be dangerous until they have found out
how the drugs affect them.
Nonsteroidal anti-inflammatory drugs make
some people more sensitive to sunlight. Even brief
exposure to sunlight can cause severe sunburn, rashes,
redness, itching, blisters, or discoloration. Vision
changes also may occur. To reduce the chance of
these problems, avoid direct sunlight, especially from
mid-morning to mid-afternoon; wear protective clothing, a hat, and sunglasses; and use a sunscreen with a
skin protection factor (SPF) rating of at least 15. Do
not use sunlamps, tanning booths or tanning beds
while taking these drugs.
GALE ENCYCLOPEDIA OF MEDICINE

Special conditions
People with certain medical conditions and people
who are taking some other medicines can have problems if they take nonsteroidal anti-inflammatory
drugs. Before taking these drugs, be sure to let the
physician know about any of these conditions:
ALLERGIES. Let the physician know about any
allergies to foods, dyes, preservatives, or other substances. Anyone who has had reactions to nonsteroidal anti-inflammatory drugs in the past should also
check with a physician before taking them again.
PREGNANCY. Women who are pregnant or who
plan to become pregnant should check with their physicians before taking these medicines. Whether nonsteroidal anti-inflammatory drugs cause birth defects
in people is unknown, but some do cause birth defects
in laboratory animals. If taken late in pregnancy, these
drugs may prolong pregnancy, lengthen labor time,
cause problems during delivery, or affect the heart or
blood flow of the fetus.
BREASTFEEDING. Some nonsteroidal anti-inflammatory drugs pass into breast milk. Women who are
breastfeeding should check with their physicians
before taking these drugs.
OTHER MEDICAL CONDITIONS. A number of medical conditions may influence the effects of nonsteroidal anti-inflammatory drugs. Anyone who has any of
the conditions listed below should tell his or her physician about the condition before taking nonsteroidal
anti-inflammatory drugs.


stomach or intestinal problems, such as colitis or
Crohn’s disease



liver disease



current or past kidney disease; current or past kidney
stones



heart disease



high blood pressure



blood disorders, such as anemia, low platelet count,
low white blood cell count



bleeding problems



diabetes mellitus



hemorrhoids, rectal bleeding, or rectal irritation



asthma



Parkinson’s disease



epilepsy



systemic lupus erythematosus
2631

Nonsteroidal anti-inflammatory drugs

serious (See Side effects). These side effects are more
likely when the drugs are taken in large doses or for a
long time or when two or more nonsteroidal antiinflammatory drugs are taken together. Health care
professionals can help patients weigh the risks of benefits of taking these medicines for long periods.

Nonsteroidal anti-inflammatory drugs



diseases of the blood vessels, such as polymyalgia
rheumatica and temporal arteritis



severe pain, cramps, or burning in the stomach or
abdomen



fluid retention



convulsions



alcohol abuse



fever



mental illness.



severe nausea, heartburn, or indigestion



white spots or sores in the mouth or on the lips



rashes or red spots on the skin



any unusual bleeding, including nosebleeds, spitting
up or vomiting blood or dark material



black, tarry stool



chest pain



unusual bruising



severe headaches

People who have sores or white spots in the mouth
should tell the physician about them before starting to
take nonsteroidal anti-inflammatory drugs. Sores or
white spots that appear while taking the drug can be a
sign of serious side effects.
SPECIAL DIETS. Some nonsteroidal anti-inflamma-

tory drugs contain sugar or sodium, so anyone on a
low-sugar or low-sodium diet should be sure to tell his
or her physician.
SMOKING. People who smoke cigarettes may be

more likely to have unwanted side effects from this
medicine.
USE OF CERTAIN MEDICINES. Taking nonsteroidal
anti-inflammatory drugs with certain other drugs may
affect the way the drugs work or increase the risk of
unwanted side effects. (See Interactions.)

Side effects
The most common side effects are stomach pain
or cramps, nausea, vomiting, indigestion, diarrhea,
heartburn, headache, dizziness or lightheadedness,
and drowsiness. As the patient’s body adjusts to the
medicine, these symptoms usually disappear. If they
do not, check with the physician who prescribed the
medicine.
Serious side effects are rare, but do sometimes
occur. If any of the following side effects occur, stop
taking the medicine and get emergency medical care
immediately:

A number of less common, temporary side effects
are also possible. They usually do not need medical
attention and will disappear once the body adjusts to
the medicine. If they continue or interfere with normal
activity, check with the physician. Among these side
effects are:


gas, bloating, or constipation



bitter taste or other taste changes



sweating



restlessness, irritability, anxiety



trembling or twitching

Some patients who have had problems with side
effects from NSAIDs may benefit from acupuncture as
an adjunctive treatment in pain management. A recent
study done in New York found that older patients
with lower back pain related to cancer reported that
their pain was relieved by acupuncture with fewer side
effects than those caused by NSAIDs.

Interactions



swelling or puffiness of the face



swelling of the hands, feet, or lower legs



rapid weight gain



fainting



breathing problems



fast or irregular heartbeat

Nonsteroidal anti-inflammatory drugs may interact with a variety of other medicines. When this happens, the effects of the drugs may change, and the risk
of side effects may be greater. Anyone who takes these
drugs should let the physician know all other medicines
he or she is taking. Among the drugs that may interact
with nonsteroidal anti-inflammatory drugs are:



tightness in the chest



blood thinning drugs, such as warfarin (Coumadin)



other nonsteroidal anti-inflammatory drugs



heparin



tetracyclines



cyclosprorine

Other side effects do not require emergency medical care, but should have medical attention. If any
of the following side effects occur, stop taking the
medicine and call the physician who prescribed the
medicine as soon as possible:
2632

GALE ENCYCLOPEDIA OF MEDICINE

Anemia—A lack of hemoglobin—the compound in
blood that carries oxygen from the lungs throughout the body and brings waste carbon dioxide from
the cells to the lungs, where it is released.
Bursitis—Inflammation of the tissue around a joint.
Colitis—Inflammation of the colon (large bowel.
COX-2 inhibitors—A class of newer NSAIDs that
are less likely to cause side effects in the digestive
tract. COX-2 inhibitors work by inhibiting the production of cyclooxygenase-2, an enzyme involved
in inflammation.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Salicylates—A group of drugs that includes aspirin
and related compounds. Salicylates are used to
relieve pain, reduce inflammation, and lower fever.
Tendinitis—Inflammation of a tendon, which is a
tough band of tissue that connects muscle to bone.



digitalis drugs



lithium



phenytoin (Dilantin)



zidovudine (AZT, Retrovir).

NSAIDs may also interact with certain herbal
preparations sold as dietary supplements. Among the
herbs known to interact with NSAIDs are bearberry
(Arctostaphylos uva-ursi), feverfew (Tanacetum
parthenium), evening primrose (Oenothera biennis),
and gossypol, a pigment obtained from cottonseed
oil and used as a male contraceptive. In most cases,
the herb increases the tendency of NSAIDs to irritate
the digestive tract. It is just as important for patients to
inform their doctor of herbal remedies that they take
on a regular basis as it is to give the doctor a list of their
other prescription medications.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Drug Therapy in the Elderly.’’ Section 22, Chapter 304
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine,
Part I: Western Herbal Medicine. New York: Simon
and Schuster, 2002.
GALE ENCYCLOPEDIA OF MEDICINE

Wilson, Billie Ann, RN, PhD, Carolyn L. Stang, PharmD,
and Margaret T. Shannon, RN, PhD. Nurses Drug
Guide 2000. Stamford, CT: Appleton and Lange, 1999.
PERIODICALS

Birbara, C. A., A. D. Puopolo, D. R. Munoz, et al.
‘‘Treatment of Chronic Low Back Pain with Etoricoxib,
A New Cyclo-Oxygenase-2 Selective Inhibitor:
Improvement in Pain and Disability—A Randomized,
Placebo-Controlled, 3-Month Trial.’’ Journal of Pain 4
(August 2003): 307–315.
Gordon, D. B. ‘‘Nonopioid and Adjuvant Analgesics in
Chronic Pain Management: Strategies for Effective
Use.’’ Nursing Clinics of North America 38 (September
2003): 447–464.
Graf, C., and K. Puntillo. ‘‘Pain in the Older Adult in the
Intensive Care Unit.’’ Critical Care Clinics 19 (October
2003): 749–770.
Harris, R. E., R. T. Chlebowski, R. D. Jackson, et al.
‘‘Breast cancer and Nonsteroidal Anti-Inflammatory
Drugs: Prospective Results from the Women’s Health
Initiative.’’ Cancer Research 63 (September 15, 2003):
6096–6101.
Hatsiopoulou, O., R. I. Cohen, and E. V. Lang.
‘‘Postprocedure Pain Management of Interventional
Radiology Patients.’’ Journal of Vascular and
Interventional Radiology 14 (November 2003): 1373–
1385.
Meng, C. F., D. Wang, J. Ngeow, et al. ‘‘Acupuncture for
Chronic Low Back Pain in Older Patients: A
Randomized, Controlled Trial.’’ Rheumatology
(Oxford) 42 (December 2003): 1508–1517.
Perrone, M. R., M. C. Artesani, M. Viola, et al.
‘‘Tolerability of Rofecoxib in Patients with Adverse
Reactions to Nonsteroidal Anti-Inflammatory Drugs:
A Study of 216 Patients and Literature Review.’’
International Archives of Allergy and Immunology 132
(September 2003): 82–86.
Raffa, R. B., R. Clark-Vetri, R. J. Tallarida, and A. I.
Wertheimer. ‘‘Combination Strategies for Pain
Management.’’ Expert Opinion in Pharmacotherapy 4
(October 2003): 1697–1708.
Small, R. C., and A. Schuna. ‘‘Optimizing Outcomes in
Rheumatoid Arthritis.’’ Journal of the American
Pharmaceutical Association 43, no. 5, Supplement 1
(September-October 2003): S16–S17.
Stephens, J., B. Laskin, C. Pashos, et al. ‘‘The Burden of
Acute Postoperative Pain and the Potential Role of the
COX-2-Specific Inhibitors.’’ Rheumatology (Oxford)
42, Supplement 3 (November 2003): iii40–iii52.
ORGANIZATIONS

U. S. Food and Drug Administration (FDA). 5600 Fishers
Lane, Rockville, MD 20857. (888) 463-6332. <http://
www.fda.gov>.

Nancy Ross-Flanigan
Rebecca J. Frey, PhD
2633

Nonsteroidal anti-inflammatory drugs

KEY TERMS

Noroviruses

Nontropical sprue see Celiac disease
Nonvenereal syphilis see Bejel
Norfloxac see Fluoroquinolones

Noroviruses
Definition
Noroviruses are a group of related, singlestranded RNA (ribonucleic acid) viruses that cause
acute gastroenteritis in humans.

The U.S. Centers for Disease Control and
Prevention (CDC) estimate that noroviruses are
responsible for some 23 million cases of acute gastroenteritis in the United States every year.
Epidemiologists estimate that about 50,000
Americans are hospitalized annually and about 400
die as a result of norovirus infection. In developing
countries noroviruses are a major cause of human
illness.
Gastroenteritis caused by infection with a norovirus is rarely a serious illness. Typically an infected
person suddenly feels very ill and may vomit many
times in a single day. The symptoms, although quite
unpleasant, usually last only 24–60 hours.
Transmission

Description
Noroviral infection
Noroviruses are a major cause of viral gastroenteritis—an inflammation of the linings of the stomach
and small and large intestines that causes vomiting and
diarrhea. Viruses are responsible for 30–40% of all
cases of infectious diarrhea and viral gastroenteritis
is the second most common illness in the United
States, exceeded only by the common cold.
Anyone can become infected with norovirus.
During norovirus outbreaks there are high rates of
infection among people of all ages. There are a large
number of genetically-distinct strains of norovirus.
Immunity appears to be specific for the norovirus
strain and lasts for only a few months. Therefore
norovirus infection can recur throughout a person s
lifetime. Because of genetic (inherited) differences
among humans, some people appear to be more susceptible to norovirus infection and may suffer more
severe illness. People with type O blood are at the
highest risk for severe infection.
Infected individuals are contagious from the first
onset of symptoms until at least three days after full
recovery. Some people may remain contagious for as
long as two weeks after recovery.
Gastroenteritis
Gastroenteritis often is referred to as the stomach
flu even though the flu is a respiratory illness caused by
an influenza virus. Other common names for viral
gastroenteritis include:


food poisoning



winter-vomiting disease



non-bacterial gastroenteritis



calicivirus infection.

2634

Noroviruses are ubiquitous in the environment.
They are highly contagious and are considered to be
among the most infectious of viruses. The reasons for
this include:


Only a small number of viral particles—fewer than
100—are required for infection.



Although noroviruses cannot reproduce outside of
their human hosts, they can remain viable for weeks
or even months on objects and surfaces.



Human immunity to norovirus is short-lived and
strain-specific.

Noroviruses are transmitted among people by a
fecal-oral route, either by ingestion of food or water
contaminated with feces or by contact with the vomit
or feces of an infected person. Norovirus infection can
occur by:


consuming contaminated food or liquids



hand contact with contaminated objects or surfaces,
followed by hand contact with the mouth



contact with an infected person, including caring for
the sick person or sharing food or utensils



aerosolized vomit that is swallowed or contaminates
surfaces.

Environmental contamination or contact with
infected clothing or linen also may be a source of
transmission. Although there is no evidence that norovirus infection can occur via the respiratory system,
the sudden and violent vomiting of noroviral gastroenteritis can lead to contamination of the surroundings and of public areas. Particles laden with virus can
be suspended in the air and swallowed.
FOODBORNE TRANSMISSION. Noroviruses account
for at least 50% of food-related outbreaks of gastroenteritis. A European study found that between 1995

GALE ENCYCLOPEDIA OF MEDICINE

Foods that frequently are associated with norovirus outbreaks include:


foods that are eaten without further cooking, including sandwiches, salads, and bakery products



liquids such as salad dressing or cake icing in which
the virus becomes evenly distributed



food that is contaminated at its source, including
oysters and clams from contaminated waters and
raspberries irrigated with sewage-contaminated
water



food that becomes contaminated before distribution,
including salads and frozen fruit.



Shellfish, including oysters and clams, concentrate
norovirus from contaminated water in their tissues.
Steaming shellfish may not completely inactivate the
virus.

WATERBORNE TRANSMISSION. There is widespread
norovirus contamination of rivers and seas, often with
more than one strain of the virus. Waterborne outbreaks of norovirus have been associated with:


sewage-contaminated wells



contaminated municipal water systems



stream and lake water



swimming pools and spas



commercial ice.

in nursing homes, 13% in schools, and 10% at resorts
or on cruise ships. Outbreaks also have occurred at
large family gatherings.
Cruise ships have become notorious for norovirus
outbreaks among passengers and staff. Cruise ships
and naval vessels are at increased risk for contamination when docking in regions that lack adequate sanitation and where contaminated food or water may be
brought onboard. Outbreaks on cruise ships are exacerbated by close living quarters and the arrival of
new, susceptible passengers every one to two weeks.
Norovirus outbreaks have been reported to continue
through more than 12 successive cruises on a single
ship.
A study of 12 calicivirus outbreaks on cruise ships
in 2002 found that 11 of the outbreaks were caused by
noroviruses and seven of these were due to a previously unreported strain. In the same year, 10 out of
22 land-based outbreaks were attributed to this new
strain.
Outbreaks of norovirus appear on the increase. In
2005 the CDC reported that norovirus outbreaks were
increasing in hospitals, daycare centers, nursing
homes, and schools across the country. The
International Council of Cruise Lines reported that,
although less than 1% of passengers become infected
with norovirus each year, outbreaks on cruise ships
also were on the increase. In the summer of 2004 an
outbreak at Yellowstone National Park sickened 134
people. More than 1,100 people became ill in early
2004 after a norovirus outbreak at Las Vegas hotels.
The following autumn more than 1,200 people became
sick from a norovirus outbreak at a single Las Vegas
hotel-casino.

Causes & symptoms
Norovirus strains

Outbreaks
Norovirus infection can spread rapidly through
daycare centers, schools, prisons, hospitals, nursing
homes, camps, and other confined spaces. About
40% of group- or institutionally-related outbreaks of
diarrhea are caused by norovirus. Outbreaks usually
peak during the winter months.
Between July of 1997 and June of 2000, 232 norovirus outbreaks were reported to the CDC. It was
determined that 57% of these outbreaks were due to
foodborne transmission, 16% were spread by human
contact, and 3% were due to waterborne transmission.
The mode of transmission could not be determined in
23% of the outbreaks. Restaurants or catered food
accounted for 36% of the outbreaks, 23% occurred
GALE ENCYCLOPEDIA OF MEDICINE

Noroviruses lack outer envelopes and their
genetic material is carried as single-stranded RNA
rather than DNA. Although noroviruses are not
new, the extent of norovirus infection was not recognized until the 1990s. This has led to increased
research on noroviruses and more monitoring of
outbreaks.
Until 2004 noroviruses were commonly referred
to as:


Norwalk virus



Norwalk-like viruses (NLVs)



caliciviruses



small, round-structured viruses (SRSVs).
2635

Noroviruses

and 2000 noroviruses were responsible for more than
85% of all foodborne non-bacterial gastroenteritis
outbreaks. Restaurant or catered foods are common
sources of norovirus transmission, with subsequent
infection of household members. The majority of
norovirus outbreaks occur via contamination by a
food handler immediately before the food is
consumed.

Noroviruses

Noroviruses are named after the original strain—
the Norwalk virus—that caused an outbreak of gastroenteritis in a Norwalk, Ohio, school in 1968. The
virus was identified in 1972. Since then many related
viruses have been identified. In 2004 these viruses were
grouped together in the genus Norovirus within the
Caliciviridae family of viruses. Eight to ten distinct genogroups of norovirus have been found in various parts
of the world. The most common genogroups are GI,
GII, GIII, and GIV. Each of these groups can be
further differentiated into at least 20 genetic clusters.
Evidence suggests that noroviruses in different genetic
clusters can recombine to form new, genetically-distinct noroviruses. GII strains, especially GII4, are the
most prevalent. However the most common method of
identifying noroviruses—the reverse transcriptionpolymerase chain reaction (RT-PCR)—may not
always identify GII genetic clusters correctly.
The increased number of norovirus outbreaks in
European countries in 2002—occurring in the spring
and summer rather than in winter—were found to be
associated with the emergence of a new variant of the
GII4 strain. Increased international outbreaks in 2003
and 2004 also were caused by a GII4-related norovirus
that was found to mutate rapidly. Mutations in the
viral capsid—the virus s outer protective layer—were
used to determine the predominant routes of norovirus transmission.
Symptoms
Symptoms of norovirus infection usually appear
within 24–48 hours after exposure, with a median
incubation period during outbreaks of 33–36 hours.
However symptoms can occur as early as 12 hours or
less after exposure.
Typical symptoms of norovirus infection are:


nausea



vomiting



watery diarrhea without blood



abdominal cramping.

Among children, vomiting is the predominant
symptom, whereas diarrhea is more common in adults.
Vomiting can be frequent and violent and may occur
without warning.
Additional symptoms of norovirus infection may
include:


low-grade fever



chills



headache

2636



muscle aches



fatigue.

Dehydration is the major risk from gastroenteritis
caused by norovirus, particularly among infants,
young children, the elderly, and those with underlying
health conditions.Symptoms of dehydration include:


dry mouth



increased or excessive thirst



low urine output



nausea



dizziness or faintness



sunken eyes



sunken fontanelle—the soft spot on an infant s head



confusion.

As many as 30–50% of norovirus infections do
not produce symptoms. It is not known whether individuals with asymptomatic infections can transmit the
virus.

Diagnosis
Identifying noroviruses
Viral gastroenteritis usually is diagnosed on the
basis of the symptoms. Many types of viruses cause
gastroenteritis. Rotoviruses are a leading cause of
gastroenteritis in children who then transmit the
virus to adults. In addition to noroviruses, viral gastroenteritis in humans can be caused by another genus
of viruses within the Caliciviridae family. Formerly
known as the Sapporo-like virus, or classic or typical
calicivirus, these now are grouped in the genus
Sapovirus. Other genera in the Caliciviridae family
are not pathogenic in humans. Some bacteria and
parasites also cause illnesses that are similar to norovirus infection.
The cloning and sequencing of noroviruses in the
early 1990s made it easier to identify norovirus outbreaks. RT-PCR is the most commonly used method
for identifying norovirus. With this technique the
virus s RNA is used as the template for transcribing
the corresponding DNA using the enzyme reverse
transcriptase. The DNA is amplified into many copies
using the polymerase chain reaction. Many state public health laboratories use this method to detect norovirus in vomit and stools. The best identification
usually comes from stool samples taken within 48–72
hours after the onset of symptoms; however norovirus
can be detected in stool samples taken five days after
GALE ENCYCLOPEDIA OF MEDICINE

Norovirus from fecal samples can be visualized
using electron microscopy. With immune electron
microscopy (IEM), antibodies against norovirus are
collected from blood serum and used to trap and
visualize the virus from fecal samples. However these
methods require high concentrations of norovirus in
the stool, as well as a fourfold increase in norovirusspecific antibodies in blood samples taken during the
acute or recovery phases of gastroenteritis.
Enzyme-linked immunosorbent assays may be
used to detect noroviruses in fecal samples. In these
assays noroviral-specific antibodies bound to the virus
are detected by the reaction of an enzyme that is
attached to the antibody. Nucleic acid probes that
hybridize with noroviral RNA also can be used for
virus detection in feces.
As of 2005 a Japanese chemical company was
producing a reagent kit that can be used to detect
norovirus in two hours rather than the 12–24 hours
needed for conventional detection. Other simpler
methods for rapidly identifying norovirus are under
development.
Investigating outbreaks
Epidemiological studies often involve sequencing
the norovirus RNA. This can help to determine
whether outbreaks in different geographical locations
are connected to each other and can help trace the
source of the norovirus to contaminated food or
water. CaliciNet is a database that stores the RNA
sequences of all norovirus strains that cause gastroenteritis in the United States.
Criteria that are sometimes used to determine
whether an outbreak of gastroenteritis is caused by a
norovirus include:


a mean incubation period of 24–48 hours



a mean duration time for illness of 12–60 hours



vomiting in more than 50% of patients



failure to find a bacterial cause for the illness.

During investigations of norovirus outbreaks,
food handlers may be asked to provide a stool sample
and possibly a blood sample. Food rarely is tested for
norovirus since each type of food requires a specific
assay. However tests are used to detect the virus in
shellfish. When large amounts—1–26 gal. (5–100 L)—
of water are processed through specially designed filters, the norovirus can be concentrated and assayed by
RT-PCR.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Gastroenteritis caused by noroviruses usually
resolves itself without treatment within a very few
days. As of 2005 there are no medications or vaccines
that are effective against the norovirus. Viruses are not
affected by antibiotics and antidiarrheal medications
may prolong the infection.
Norovirus infections should be treated by:


drinking plenty of fluids, such as water and juice, to
prevent dehydration caused by vomiting and
diarrhea



intravenous fluids if severe nausea prevents drinking,
particularly in small children



drinking oral rehydration fluids (ORFs) to prevent
dehydration and to replace electrolytes (salt and
minerals) and glucose



avoiding alcohol and caffeine which can increase
urination.

Commercially
available
ORFs
include
Naturalyte, Pedialyte, Infalyte, and Rehydralyte.
Juice, soda, and water do not replace lost electrolytes; nor do sports drinks replace nutrients and minerals lost through vomiting and diarrhea. Those taking
diuretics should ask their healthcare provider whether
to stop taking the medication during acute diarrhea.
Since the risk of dehydration is higher for infants
and young children, the number of wet diapers per day
should be closely monitored. Severely dehydrated children may receive rapid intravenous rehydration in a
hospital or emergency-room setting.
A health care provider should be consulted if:


symptoms of dehydration appear



diarrhea persists for longer than a few days



there is blood in the stool.

Alternative treatment
An infusion of meadowsweet (Filipendula
ulmaria) may reduce nausea. Once the symptoms are
reduced, slippery elm (Ulmus fulva may calm the digestive system. Castor oil packs placed on the abdomen
can reduce inflammation and discomfort.
Homeopathic remedies for gastroenteritis include
Arsenicum album, ipecac, and Nux vomica. Chinese
patent herbal remedies include Po Chai and Pill
Curing.
During recovery from viral gastroenteritis, live
cultures of Lactobacillus acidophilus, found in
2637

Noroviruses

the onset of symptoms and sometimes even in samples
taken up to two weeks after recovery.

Noroviruses

live-culture yogurt or as powder or capsules, may be
useful for restoring the native flora of the digestive tract.

with a minimum of handling, followed by machine
drying.


Vomit and feces should be discarded or flushed
immediately and the toilet area should be kept clean.



Exposed or contaminated food should be discarded.



Masks may be worn while cleaning areas that have
been badly contaminated with vomit or feces, such as
in hospitals or nursing homes.

Prognosis
Norovirus infection is followed by complete
recovery and there are no known long-term health
effects. Infected persons do not become long-term
carriers of the virus. Dehydration is the most serious
possible consequence of noroviral infection and can be
fatal, particularly among older people with debilitating medical conditions or impaired immune systems.

Prevention
Noroviruses are difficult to destroy. They can
survive freezing as well as temperatures as high as
140 ˚ F (60 ˚ C). Noroviruses can survive chlorine levels
as high as 10 parts per million (ppm), far higher than
the levels present in most public water systems. A 2004
study from the Netherlands found that inactivation of
norovirus with 70% ethanol was inefficient and that
sodium hypochlorite solutions were effective only at
concentrations above 300 ppm.
The best prevention against noroviral infection is
frequent, thorough hand washing with soap and
water. All soaped hand surfaces should be rubbed
vigorously for at least 10 seconds. The hands should
be thoroughly rinsed under a stream of water. In
particular hands always should be washed before
handling food and after using the toilet or changing
diapers.
Other important measures for preventing norovirus infection include:


proper handling of cold foods



careful washing of fruits and vegetables



steaming oysters before eating, although even this
may be insufficient for destroying norovirus



taking particular care when handing the diapers of
children with diarrhea



properly disposing of sewage and diapers



excluding sick infants and children from food preparation areas.
To prevent further transmission of norovirus:





All surfaces exposed to vomit or otherwise contaminated should be immediately cleaned and disinfected
with a solution of 10% bleach, followed by rinsing.
Contaminated clothing and linens should be
removed immediately and washed with hot water
and detergent on the maximum machine cycle and

2638

A 2004 study found that detergent-based cleaning
with a cloth consistently failed to eliminate norovirus
contamination. With fecal contamination, detergentbased cleaning, followed by cleaning with a combination hypochlorite/detergent formula containing 5000
ppm of available chlorine significantly reduced contamination. However norovirus still could be detected
on as much as 28% of the surfaces. When this procedure failed to eliminate contamination, the virus was
transmitted to the cleaner’s hands. Contaminated fingers consistently transferred norovirus to up to seven
different surfaces including doorknobs and telephones. However the contamination was diluted during secondary transmission and treatment with the
combined bleach/detergent eliminated the virus without prior cleaning.
In situations where there is a periodic renewal of
susceptible people, such as on cruise ships and at
camps, the facility may have to be closed until cleaning
is complete. Although many state and local health
departments require that food handlers with gastroenteritis not return to work until 2–3 days following
recovery, this may not be an adequate length of time to
prevent noroviral transmission.
The prevention of norovirus outbreaks include
reducing contamination of water supplies with
human waste and using high-level chlorination—at
least 10 ppm for more than 30 min. Surveillance of
shorelines for potential sources of fecal contamination
and for boats that are dumping human waste may help
prevent shellfish-associated norovirus outbreaks.
In 2004 researchers at Washington University
announced that they had succeeded in growing a
mouse norovirus in the laboratory for the first time,
with the goal of studying the virus and developing a
vaccine against it. New surveillance systems also are
being developed to detect norovirus outbreaks at an
early stage.
Resources
BOOKS

Richman, Douglas D., et al., editors. Clinical Virology. 2nd
ed. Washington, D.C.: ASM Press, 2002.
GALE ENCYCLOPEDIA OF MEDICINE

Antibody—A blood protein produced in response
to foreign material such as a virus; the antibody
attaches to the virus and destroys it.
Calicivirus—A member of the Caliciviridae family
of viruses that includes noroviruses.
Capsid—The outer protein coat of a virus.
Gastroenteritis—An inflammation of the lining of
the stomach and intestines, usually caused by a
viral or bacterial infection.
Genetic cluster—A group of viral strains with very
similar, yet distinct, nucleic acid sequences.
Genogroup—Related viruses within a genus; may
be further subdivided into genetic clusters.
Reverse transcription-polymerase chain reaction;
RT-PCR—A method of polymerase-chain-reaction
amplification of nucleic acid sequences that uses
RNA as the template for transcribing the corresponding DNA using reverse transcriptase.

DC 20013-1133. healthfinder@nhic.org. <http://
www.healthfinder.gov/>.
Office of Health Communication. National Center for
Infectious Diseases. Centers for Disease Control and
Prevention. Mailstop C-14, 1600 Clifton Road,
Atlanta, GA 30333. 800-311-3435. <http://
www.cdc.gov/ncidod/index.htm>.
OTHER

PM Medical Health News. 21st Century Complete Medical
Guide to Gastroenteritis, Norwalk Virus, Norovirus,
Authoritative Government Documents, Clinical
References, and Practical Information for Patients and
Physicians. CD-ROM. Progressive Management, 2004.
Norovirus. Respiratory and Enteric Viruses Branch,
National Center for Infectious Diseases. January 20,
2005 [cited February 21, 2005]. <http://www.cdc.gov/
ncidod/dvrd/revb/gastro.norovirus.htm>.
‘‘Norovirus Cultured for the First Time.’’ Public Library of
Science Biology 2.12 (2004). November 30, 2004 [cited
February 26, 2005]. <http://www.plosbiology.org/
plosonline/?request=get-document&doi=10.1371%2
Fjournal.pbio.0020445>.

Margaret Alic, Ph.D.

Norplant see Depo-Provera/Norplant
PERIODICALS

Blevins, L. Zanardi, et al. ‘‘An Outbreak of Norovirus
Gastroenteritis at a Swimming Club—Vermont, 2004.’’
MMWR. Morbidity and Mortality Weekly Report 53,
no. 34 (September 3, 2004): 793-5.
Centers for Disease Control and Prevention, National
Center for Infectious Diseases. ‘‘Norwalk-Like Viruses:
Public Health Consequences and Outbreak
Management.’’ MMWR. Morbidity and Mortality
Weekly Report 50, no. RR-9 (June 1, 2001).
Kirkwood, Chris. ‘‘Viral Gastroenteritis in Europe: A New
Norovirus Variant?’’ The Lancet 363, no. 9410
(February 28, 2004): 671-2.
Lopman, Ben, et al. ‘‘Increase in Viral Gastrocenteritis
Outbreaks in Europe and Epidemic Spread of New
Norovirus Variant.’’ The Lancet 363, no. 9410
(February 28, 2004): 682-8.
‘‘Norovirus; Cruise Ships Experience Increase in Norovirus
Incidents.’’ Science Letter February 22, 2005: 1140.
‘‘Norovirus; Detergent Followed by Bleach/Detergent
Reduces Norovirus Contamination.’’ Science Letter
December 14, 2004: 843.
‘‘Norovirus Outbreak; Alterations to Norovirus Capsid
Structure Explains 2002–2003 Outbreaks.’’ Science
Letter November 30, 2004: 1008.
ORGANIZATIONS

National Health Information Center. Office of Disease
Prevention and Health Promotion. U.S. Department of
Health & Human Services. P.O. Box 1133, Washington,
GALE ENCYCLOPEDIA OF MEDICINE

Norwalk virus infection see Gastroenteritis
Nose injuries see Nasal trauma
Nose irrigation see Nasal irrigation
Nose job see Rhinoplasty
Nose packing see Nasal packing
Nose papillomas see Nasal papillomas
Nose polyps see Nasal polyps

Nosebleed
Definition
A nosebleed is bleeding from the nose; the medical
term for it is epistaxis.

Description
Unexpected bleeding from anywhere is cause for
alarm. Persistent bleeding should always be investigated because it may be the earliest sign of cancer.
Fortunately, nosebleeds are rarely a sign of cancer. A
much more common cause of nosebleeds is injury
from picking or blowing or fisticuffs. People with
2639

Nosebleed

KEY TERMS

Nosebleed

hay fever have swollen membranes that are fragile and
more likely to bleed.
Most nosebleeds (about 90%) come from the
front of the septum, that plane of cartilage that separates the nostrils. These are called anterior nosebleeds.
The lower front part of the septum has a mass of blood
vessels on either side called Kiesselbach’s plexus that is
easy to injure. Nosebleeds from the more remote
reaches of the nose are called posterior nosebleeds.
They are less common, are less likely to have a benign
cause, and are much harder to manage.
Nosebleeds are most likely to occur in children
between the ages of two and 10 years, in part because
younger children frequently insert small objects in the
nose or pick at the tissues lining the nose. Nosebleeds
in adolescents may indicate cocaineabuse. Nosebleeds
in older adults may result from arteriosclerosis or high
blood pressure.

Causes and symptoms
Nosebleeds may result from a number of different
causes:


local infections (colds, sinus infections)



systemic infections (scarlet fever, typhoid fever,
malaria)



drying of the membranes lining the nose, often during heating season in colder climates



medications, most commonly, overuse of nasal
decongestant sprays



trauma (from foreign objects in the nose; scratching
or picking with the fingers; or blunt trauma to the
face)



tumors in the nasopharynx or paranasal sinuses



cocaine abuse



bleeding disorders (leukemia, liver disease, hemophilia and other hereditary clotting disorders)

Treatment
The first treatment is to pinch the patient’s nostrils
together, have them sit forward, and ask them to stay
that way for 5–10 minutes. This method usually stops
nosebleeds originating in Kiesselbach’s plexus. The
patient should not tilt his or her head backward, as
this position may cause blood to drip backward into
the throat or windpipe. It is best to hold the head
upright.
In the case of small children, the doctor may
examine the inside of the nose to check for foreign
2640

bodies, evidence of scratching or picking, etc. Small
foreign bodies (watch batteries, dried peas or beans,
buttons, etc.) can be removed by suction if necessary.
The doctor may also have to remove clotted blood by
suction.
Bleeding that continues originates from the back
of the nose in most cases and will flow down the
throat. If that happens, emergency intervention is
needed.
As an emergency procedure, the nose will be
packed front and/or back with cotton gauze and a
rubber balloon from a Foley catheter. This treatment
is not comfortable. Having no place to flow, the blood
should clot, giving the ear, nose and throat specialists
(otorhinolaryngologists) a chance to find the source
and permanently repair it. If the packing has to remain
for any length of time, antibiotics and pain medication
will be necessary—antibiotics because the sinuses will
be plugged up and prone to infection. Nose packing
may so interfere with breathing that the patient will
need supplemental oxygen.
Newer options for controlling posterior nosebleeds include the use of Surgicel, Merocel, or other
oxidized cellulose products that expand with moisture.
These may control the bleeding without the need for
bulky nasal packing.
Many bleeds are from small exposed blood vessels
with no other disease. They can be destroyed by cautery, usually done by applying silver nitrate to the
affected area. Larger vessels may not respond to cautery. The surgeon may have to tie them off, which is
known as ligation. Another technique that is sometimes used with larger vessels is embolization, in which
the doctor injects a chemical to block or close the
blood vessel.

Alternative treatment
Estrogen cream, the same preparation used to
revitalize vaginal tissue, can toughen fragile blood
vessels in the anterior septum and forestall the need
for cauterization. Botanical medicines known as styptics, which slow down and can stop bleeding, may be
taken internally or applied topically. Some of the
plants used are achillea (yarrow), trillium, geranium,
and shepherd’s purse (capsella-bursa). Homeopathic
remedies can be one of the quickest and most effective
treatments for epistaxis.

Prevention
Both before and after a nosebleed, the patient
should blow the nose gently and avoid picking or
GALE ENCYCLOPEDIA OF MEDICINE

Cautery—The use of heat, electricity, or chemicals
to destroy tissue.
Embolization—A technique for stopping bleeding
by introducing a substance into larger blood vessels
that blocks or closes them.

American Academy of Otolaryngology—Head and Neck
Surgery. One Prince Street, Alexandria, VA 223143357. (703) 836-4444. <http://www.entnet.org>.

J. Ricker Polsdorfer, MD
Rebecca J. Frey, PhD

Nosocomial infections see Hospitalacquired infections

Epistaxis—The medical term for nosebleed.
Kiesselbach’s plexus—An area on the anterior part
of the nasal septum that has a rich supply of blood
vessels and is a common site of nosebleeds. It is
named for Wilhelm Kiesselbach, a nineteenth-century German otolaryngologist.
Septum—The partition that separates the two nostrils. It consists of membranes, cartilage, and
bone.

Nuclear magnetic resonance see Magnetic
resonance imaging

Styptic—Any remedy with an astringent and hemostatic (stopping bleeding) quality.

Nucleoside analogs see Antiretroviral drugs

scratching the tissues that line it. Children with recurrent nosebleeds during heating season may benefit
from the use of a cool-mist vaporizer to humidify the
bedroom at night, or from the application of a small
quantity of petroleum jelly to the inside of each nostril.
Treatment of hay fever helps reduce the fragility of the
tissues.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Epistaxis.’’ Section 7, Chapter 86 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PERIODICALS

Bhatnagar, R. K., and S. Berry. ‘‘Selective Surgicel Packing
for the Treatment of Posterior Epistaxis.’’ Ear, Nose,
and Throat Journal 83 (September 2004): 633–634.
Gluckman, William, DO, and Robert Baricella, DO.
‘‘Epistaxis.’’ eMedicine October 11, 2004. <http://
emedicine.com/ped/topic1618.htm>.
Gurney, T. A., C. F. Dowd, and A. H. Murr. ‘‘Embolization
for the Treatment of Idiopathic Posterior Epistaxis.’’
American Journal of Rhinology 18 (September-October
2004): 335–339.
ORGANIZATIONS

American Academy of Family Physicians (AAFP). 11400
Tomahawk Creek Parkway, Leawood, KS 66211-2672.
(800) 274-2237 or (913) 906-6000. <http://
www.aafp.org>.
GALE ENCYCLOPEDIA OF MEDICINE

NS see Nephrotic syndrome
NSAIDs see Nonsteroidal anti-inflammatory
drugs
Nther’s disease see Porphyrias

Numbness and tingling
Definition
Numbness and tingling are decreased or abnormal sensations caused by altered sensory nerve
function.

Description
The feeling of having a foot ‘‘fall asleep’’ is a
familiar one. This same combination of numbness
and tingling can occur in any region of the body and
may be caused by a wide variety of disorders.
Sensations such as these, which occur without any
associated stimulus, are called paresthesias. Other
types of paresthesias include feelings of cold, warmth,
burning, itching, and skin crawling.

Causes and symptoms
Causes
Sensation is carried to the brain by neurons (nerve
cells) running from the outer parts of the body to the
spinal cord in bundles called nerves. In the spinal cord,
these neurons make connections with other neurons
that run up to the brain. Paresthesias are caused by
disturbances in the function of neurons in the sensory
pathway. This disturbance can occur in the central
nervous system (the brain and spinal cord), the nerve
roots that are attached to the spinal cord, or the
2641

Numbness and tingling

KEY TERMS

Numbness and tingling

peripheral nervous system (nerves outside the brain
and spinal cord).
Peripheral disturbances are the most common
cause of paresthesias. ‘‘Falling asleep’’ occurs when
the blood supply to a nerve is cut off—a condition
called ischemia. Ischemia usually occurs when an
artery is compressed as it passes through a tightly
flexed joint. Sleeping with the arms above the head
or sitting with the legs tightly crossed frequently cause
numbness and tingling.
Direct compression of the nerve also causes paresthesias. Compression can be short-lived, as when a
heavy backpack compresses the nerves passing across
the shoulders. Compression may also be chronic.
Chronic nerve compression occurs in entrapment syndromes. The most common example is carpal tunnel
syndrome. Carpal tunnel syndrome occurs when the
median nerve is compressed as it passes through a
narrow channel in the wrist. Repetitive motion or
prolonged vibration can cause the lining of the channel to swell and press on the nerve. Chronic nerve root
compression, or radiculopathy, can occur in disk disease or spinal arthritis.
Other causes of paresthesias related to disorders
of the peripheral nerves include:


Metabolic or nutritional disturbances. These disturbances include diabetes, hypothyroidism (a condition
caused by too little activity of the thyroid gland),
alcoholism, malnutrition, and vitamin B12 deficiency.



Trauma. Trauma includes injuries that crush, sever,
or pull on nerves.



Inflammation.



Connective tissue disease. These diseases include
arthritis, systemic lupus erythematosus (a chronic
inflammatory disease that affects many systems of
the body, including the nervous system), polyarteritis
nodosa (a vascular disease that causes widespread
inflammation and ischemia of small and mediumsize arteries), and Sjögren’s syndrome (a disorder
marked by insufficient moisture in the tear ducts,
salivary glands, and other glands).



Toxins. Toxins include heavy metals (metallic elements such as arsenic, lead, and mercury which can,
in large amounts, cause poisoning), certain antibiotics
and chemotherapy agents, solvents, and overdose of
pyridoxine (vitamin B6).



Hereditary disease. These diseases include CharcotMarie-Tooth disease (a hereditary disorder that
causes wasting of the leg muscles, resulting in malformation of the foot), porphyria (a group of inherited disorders in which there is abnormally increased
production of substances called porphyrins), and
Denny-Brown’s syndrome (a hereditary disorder of
the nerve root).

Paresthesias can also be caused by central nervous
system disturbances, including stroke, TIA (transient
ischemic attack), tumor, trauma, multiple sclerosis, or
infection.
Symptoms
Sensory nerves supply or innervate particular
regions of the body. Determining the distribution of
symptoms is an important way to identify the nerves
involved. For instance, the median nerve innervates
the thumb, the first two fingers, half of the ring finger,
and the part of the hand to which they connect. The
ulnar nerve innervates the other half of the ring finger,
the little finger, and the remainder of the hand.
Distribution of symptoms may also aid diagnosis of
the underlying disease. Diabetes usually causes a symmetrical ‘‘glove and stocking’’ distribution in the
hands and feet. Multiple sclerosis may cause symptoms in several, widely separated areas.
Other symptoms may accompany paresthesias,
depending on the type and severity of the nerve disturbance. For instance, weakness may accompany
damage to nerves that carry both sensory and motor
neurons. (Motor neurons are those that carry messages outward from the brain.)

Diagnosis
A careful history of the patient is needed for a
diagnosis of paresthesias. The medical history should
focus on the onset, duration, and location of symptoms. The history may also reveal current related
medical problems and recent or past exposure to
drugs, toxins, infection, or trauma. The family medical
history may suggest a familial disorder. A work history may reveal repetitive motion, chronic vibration,
or industrial chemical exposure.



Malignancy.

The physical and neurological examination tests
for distribution of symptoms and alterations in
reflexes, sensation, or strength. The distribution of
symptoms may be mapped by successive stimulation
over the affected area of the body.



Infections. Infections include Lyme disease, human
immunodeficiency virus (HIV), and leprosy.

Lab tests for paresthesia may include blood tests
and urinalysis to detect metabolic or nutritional

2642

GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Treatment of paresthesias depends on the underlying cause. For limbs that have ‘‘fallen asleep,’’ restoring circulation by stretching, exercising, or massaging
the affected limb can quickly dissipate the numbness
and tingling. If the paresthesia is caused by a chronic
disease such as diabetes or occurs as a complication of
treatments such as chemotherapy, most treatments are
aimed at relieving symptoms. Anti-inflammatory drugs
such as aspirin or ibuprofen are recommended if symptoms are mild. In more difficult cases, antidepressant
drugs such as amitriptyline (Elavil) are sometimes prescribed. These drugs are given at a much lower dosage
for this purpose than for relief of depression. They are
thought to help because they alter the body’s perception
of pain. In severe cases, opium derivatives such as
codeine can be prescribed. Currently trials are being
done to determine whether treatment with human
nerve growth factor will be effective in regenerating
the damaged nerves.

Alternative treatment
Several alternative treatments are available to
help relieve symptoms of paresthesia. Nutritional
therapy includes supplementation with B complex
vitamins, especially vitamin B 12 (intramuscular injection of vitamin B12 is most effective). Vitamin supplements should be used cautiously however. Overdose of
Vitamin B6 is one of the causes of paresthesias. People
experiencing paresthesia should also avoid alcohol.
Acupuncture and massage are said to relieve symptoms. Self-massage with aromatic oils is sometimes
helpful. The application of topical ointments containing capsaicin, the substance that makes hot peppers
hot, provides relief for some. It may also be helpful to
wear loosely fitting shoes and clothing. None of these
alternatives should be used in place of traditional
therapy for the underlying condition.

KEY TERMS
Electromyography—A test that uses electrodes to
record the electrical activity of muscle. The information gathered is used to diagnose neuromuscular
disorders.
Motor nerve—Motor or efferent nerve cells carry
impulses from the brain to muscle or organ tissue.
Nerve conduction velocity test—A test that measures the time it takes a nerve impulse to travel a
specific distance over the nerve after electronic
stimulation.
Nerve growth factor—A protein resembling insulin that affects growth and maintenance of nerve
cells
Peripheral nervous system—The part of the nervous system that is outside the brain and spinal
cord. Sensory, motor, and autonomic nerves are
included.
Sensory nerves—Sensory or afferent nerves carry
impulses of sensation from the periphery or outward parts of the body to the brain. Sensations
include feelings, impressions, and awareness of
the state of the body.

Prevention
Preventing the underlying disorder may reduce
the incidence of paresthesias. For those with frequent
paresthesias caused by ischemia, changes in posture
may help.
Resources
PERIODICALS

McKnight, Jerry T., and Bobbi B. Adcock. ‘‘Paresthesias:
A Practical Diagnostic Approach.’’ American Family
Physician 56 (December 1997): 2253-2260.

Richard Robinson

Nummular dermatitis see Dermatitis

Prognosis
Treating the underlying disorder may reduce the
occurrence of paresthesias. Paresthesias resulting from
damaged nerves may persist throughout or even
beyond the recovery period. The overall prognosis
depends on the cause.
GALE ENCYCLOPEDIA OF MEDICINE

Nutrition
Definition
Good nutrition can help prevent disease and promote health. There are six categories of nutrients that
2643

Nutrition

abnormalities. Other tests are used to look for specific
suspected causes. Nerve conduction velocity tests,
electromyography, and imaging studies of the affected
area may be employed. Nerve biopsy may be indicated
in selected cases.

Nutrition

the body needs to acquire from food: protein, carbohydrates, fat, fibers, vitamins and minerals, and water.
Proteins
Protein supplies amino acids to build and maintain healthy body tissue. There are 20 amino acids
considered essential because the body must have all
of them in the right amounts to function properly.
Twelve of these are manufactured in the body but the
other eight amino acids must be provided by the diet.
Foods from animal sources such as milk or eggs often
contain all these essential amino acids while a variety
of plant products must be taken together to provide all
these necessary protein components.
Fat
Fat supplies energy and transports nutrients.
There are two families of fatty acids considered essential for the body: the omega-3 and omega-6 fatty acids.
Essential fatty acids are required by the body to function normally. They can be obtained from canola oil,
flaxseed oil, cold-water fish, or fish oil, all of which
contain omega-3 fatty acids, and primrose or black
currant seed oil, which contains omega-6 fatty acids.
The American diet often contains an excess of omega6 fatty acids and insufficient amounts of omega-3 fats.
Increased consumption of omega-3 oils is recommended to help reduce risk of cardiovascular diseases
and cancer and alleviate symptoms of rheumatoid
arthritis, premenstrual syndrome, dermatitis, and
inflammatory bowel disease.
Carbohydrates
Carbohydrates are the body’s main source of
energy and should be the major part of total daily
intake. There are two types of carbohydrates: simple
carbohydrates (such as sugar or honey) or complex
carbohydrates (such as grains, beans, peas, or potatoes). Complex carbohydrates are preferred because
these foods are more nutritious yet have fewer calories
per gram compared to fat and cause fewer problems
with overeating than fat or sugar. Complex carbohydrates also are preferred over simple carbohydrates by
diabetics because they allow better blood glucose
control.
Fiber
Fiber is the material that gives plants texture and
support. Although it is primarily made up of carbohydrates, it does not have a lot of calories and is usually
not broken down by the body for energy. Dietary fiber
2644

is found in plant foods such as fruits, vegetables,
legumes, nuts, and whole grains.
There are two types of fiber: soluble and insoluble.
Insoluble fiber, as the name implies, does not dissolve
in water because it contains high amount of cellulose.
Insoluble fiber can be found in the bran of grains, the
pulp of fruit and the skin of vegetables. Soluble fiber is
the type of fiber that dissolves in water. It can be found
in a variety of fruits and vegetables such as apples,
oatmeal and oat bran, rye flour, and dried beans.
Although they share some common characteristics such as being partially digested in the stomach and
intestines and have few calories, each type of fiber has
its own specific health benefits. Insoluble fiber speeds
up the transit of foods through the digestive system
and adds bulk to the stools, therefore, it is the type of
fiber that helps treat constipation or diarrhea and prevents colon cancer. On the other hand, only soluble
fiber can lower blood cholesterol levels. This type of
fiber works by attaching itself to the cholesterol so that
it can be eliminated from the body. This prevents
cholesterol from recirculating and being reabsorbed
into the bloodstream. In 2003, the World Health
Organization released a new report specifically outlining the link of a healthy diet rich in high-fiber plant
foods to preventing cancer.
Vitamins and minerals
Vitamins are organic substances present in food
and required by the body in a small amount for regulation of metabolism and maintenance of normal
growth and functioning. The most commonly known
vitamins are A, B1 (thiamine), B2 (riboflavin), B3
(niacin), B5 (pantothenic acid), B6 (pyridoxine), B7
(biotin), B9 (folic acid), B12 (cobalamin), C (ascorbic
acid), D, E, and K. The B and C vitamins are watersoluble, excess amounts of which are excreted in the
urine. The A, D, E, and K vitamins are fat-soluble and
will be stored in the body fat.
Minerals are vital to our existence because they
are the building blocks that make up muscles, tissues,
and bones. They also are important components of
many life-supporting systems, such as hormones, oxygen transport, and enzyme systems.
There are two kinds of minerals: the major (or
macro) minerals and the trace minerals. Major minerals are the minerals that the body needs in large
amounts. The following minerals are classified as
major: calcium, phosphorus, magnesium, sodium,
potassium, sulfur, and chloride. They are needed to
build muscles, blood, nerve cells, teeth, and bones.
They also are essential electrolytes that the body
GALE ENCYCLOPEDIA OF MEDICINE

Unlike the major minerals, trace minerals are
needed only in tiny amounts. Even though they can
be found in the body in exceedingly small amounts,
they are also very important to the human body. These
minerals participate in most chemical reactions in the
body. They also are needed to manufacture important
hormones. The following are classified as trace minerals: iron, zinc, iodine, copper, manganese, fluoride,
chromium, selenium, molybdenum, and boron.
Many vitamins (such as vitamins A, C, and E) and
minerals (such as zinc, copper, selenium, or manganese) act as antioxidants. They protect the body
against the damaging effects of free radicals. They
scavenge or mop up these highly reactive radicals
and change them into inactive, less harmful compounds. In so doing, these essential nutrients help
prevent cancer and many other degenerative diseases,
such as premature aging, heart disease, autoimmune
diseases, arthritis, cataracts, Alzheimer’s disease, and
diabetes mellitus.

Nutritional therapy may also be involved as a
complement to the allopathic treatments of cancer,
diabetes, and Parkinson’s disease. Other specific dietary measures include the elimination of food additives
for attention deficit hyperactivity disorder (ADHD),
gluten-free diets for schizophrenia, and dairy-free for
chronic respiratory diseases.
A high-fiber diet helps prevent or treat the following health conditions:


High cholesterol levels. Fiber effectively lowers
blood cholesterol levels. It appears that soluble
fiber binds to cholesterol and moves it down the
digestive tract so that it can be excreted from the
body. This prevents the cholesterol from being reabsorbed into the bloodstream.



Constipation. A high-fiber diet is the preferred nondrug treatment for constipation. Fiber in the diet
adds more bulk to the stools, making them softer
and shortening the time foods stay in the digestive
tract.



Hemorrhoids. Fiber in the diet adds more bulk and
softens the stool, thus, reducing painful hemorrhoidal symptoms.



Diabetes. Soluble fiber in the diet slows down the rise
of blood sugar levels following a meal and helps
control diabetes.



Obesity. Dietary fiber makes a person feel full faster.



Cancer. Insoluble fiber in the diet speeds up the
movement of the stools through the gastrointestinal
tract. The faster food travels through the digestive
tract, the less time there is for potential cancer-causing substances to work. Therefore, diets high in insoluble fiber help prevent the accumulation of toxic
substances that cause cancer of the colon. Because
fiber reduces fat absorption in the digestive tract, it
also may prevent breast cancer.

Water
Water helps to regulate body temperature, transports nutrients to cells, and rids the body of waste
materials.

Origins
Unlike plants, human beings cannot manufacture
most of the nutrients that they need to function. They
must eat plants and/or other animals. Although nutritional therapy came to the forefront of the public’s
awareness in the late twentieth century, the notion that
food affects health is not new. John Harvey Kellogg
was an early health-food pioneer and an advocate of a
high-fiber diet. An avowed vegetarian, he believed that
meat products were particularly detrimental to the
colon. In the 1870s, Kellogg founded the Battle
Creek Sanitarium, where he developed a diet based
on nut and vegetable products.

A diet low in fat also promotes good health and
prevents many diseases. Low-fat diets can help treat or
control the following conditions:


Obesity. High fat consumption often leads to excess
caloric and fat intake, which increases body fat.



Coronary artery disease. High consumption of saturated fats is associated with coronary artery disease.



Diabetes. People who are overweight tend to develop
or worsen existing diabetic conditions due to
decreased insulin sensitivity.



Breast cancer. A high dietary consumption of fat is
associated with an increased risk of breast cancer.

Purpose
Good nutrition helps individuals achieve general
health and well-being. In addition, dietary modifications might be prescribed for a variety of complaints
including allergies, anemia, arthritis, colds, depressions, fatigue, gastrointestinal disorders, high or low
blood pressure, insomnia, headaches, obesity, pregnancy, premenstrual syndrome (PMS), respiratory
conditions, and stress.
GALE ENCYCLOPEDIA OF MEDICINE

2645

Nutrition

requires to regulate blood volume and acid-base
balance.

Nutrition

Description
The four basic food groups, as outlined by the
United States Department of Agriculture (USDA)
are:


dairy products (such as milk and cheese)



meat and eggs (such as fish, poultry, pork, beef, and
eggs)



grains (such as bread cereals, rice, and pasta)



fruits and vegetables

The USDA recommendation for adults is that
consumption of meat, eggs, and dairy products should
not exceed 20% of total daily caloric intake. The rest
(80%) should be devoted to vegetables, fruits, and
grains. For children age two or older, 55% of their
caloric intake should be in the form of carbohydrates,
30% from fat, and 15% from proteins. In addition,
saturated fat intake should not exceed 10% of total
caloric intake. This low-fat, high-fiber diet is believed
to promote health and help prevent many diseases,
including heart disease, obesity, and cancer.
Allergenic and highly processed foods should be
avoided. Highly processed foods do not contain significant amounts of essential trace minerals.
Furthermore, they contain lots of fat and sugar as
well as preservatives, artificial sweeteners and other
additives. High consumption of these foods causes
build up of unwanted chemicals in the body and
should be avoided. Food allergies causes a variety of
symptoms including food cravings, weight gain, bloating, and water retention. They also may worsen
chronic inflammatory conditions such as arthritis.



grains: six or more servings



vegetables: five servings



fruits: two to four servings



meat: two to three servings



dairy: two to three servings



fats and oils: use sparingly

Precautions
Individuals should not change their diets without
the advice of nutritional experts or health care professionals. Certain individuals, especially children, pregnant and lactating women, and chronically ill patients,
only should change their diets under professional
supervision.

Side effects
It is best to obtain vitamins and minerals through
food sources. Excessive intake of vitamins and mineral
supplements can cause serious health problems.
Likewise, eating too much of one type of food, as
can happen with fad diets, can be harmful. The key
to nutrition is moderation. If a person feels they are
short on iron, for example, he or she should not go too
far to the extreme in getting more iron through diet
and supplements. A 2003 report said that too much
stored iron in the body has possibly been linked with
heart disease, cancer and diabetes.
The following is a list of possible side effects
resulting from excessive doses of vitamins and
minerals:


vitamin A: birth defects, irreversible bone and liver
damage



vitamin B1: deficiencies in B2 and B6



vitamin B6: damage to the nervous system



vitamin C: affects the absorption of copper; diarrhea



vitamin D: hypercalcemia (abnormally high concentration of calcium in the blood)



phosphorus: affects the absorption of calcium



zinc: affects absorption of copper and iron; suppresses the immune system

Preparations
An enormous body of research exists in the field of
nutrition. Mainstream Western medical practitioners
point to studies that show that a balanced diet, based
on the USDA Food Guide Pyramid, provides all of
the necessary nutrients.
In 2004, the USDA was working on a revision of
the Food Guide Pyramid to reflect changes in
American lifestyle habits. The new eating guide was
due for release in January 2005. The World Health
Organization (WHO) also was weighing in on the
obesity and nutrition issue, even struggling with objections from member nations that supply goods such as
sugar, to endorse a global strategy in spring 2004 on
diet, physical activity and health.
The Food Guide Pyramid recommends the following daily servings in six categories:
2646

Research and general acceptance
Due to a large volume of scientific evidence
demonstrating the benefits of the low-fat, high-fiber
diet in disease prevention and treatment, these recommendations have been accepted and advocated by
both complementary and allopathic practitioners.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

U.S. Preventive Services Task Force Guidelines.
‘‘Counseling to Promote a Healthy Diet.’’ Guide to
Clinical Preventive Services. 2nd ed. <http://cpmcnet.columbia.edu/texts/gcps/gcps0066.html>.
PERIODICALS

Clapp, Stephen. ‘‘World Health Assembly Adopts Global
Anti-obesity Strategy.’’ Food Chemical News May 31,
2004: 26.
Halbert, Steven C. ‘‘Diet and Nutrtion in Primary Care:
From Antioxidants to Zinc.’’ Primary Care: Clinics in
Office Practice December 1997: 825-843.
Mangels, Reed. ‘‘How Can You Avoid Having Too Much
Iron?’’ Vegetarian Journal March-April 2003: 17.
Turner, Lisa. ‘‘Good ‘n Plenty.’’ Vegetarian Times February
1999: 48.
‘‘U.N. Report Supports Key Role for Diet, Activity in Cancer
Prevention.’’ Cancer Weekly March 25, 2003: 154.
Vickers, Andrew, and Catherine Zollman. ‘‘Unconventional
approaches to nutritional medicine.’’ British Medical
Journal November 27, 1999: 1419.
ORGANIZATIONS

American Association of Nutritional Consultants. 810 S.
Buffalo Street, Warsaw, IN 46580. (888) 828-2262.
American Dietetic Association. 216 W. Jackson boulevard,
Suite 800, Chicago, IL 60606-6995. (800) 366-1655.
<http://www.eatright.org>.

Mai Tran
Teresa G. Odle

Nutrition through an
intravenous line
Definition
Sterile solutions containing some or all of the
nutrients necessary to support life, are injected into
the body through a tube attached to a needle, which is
inserted into a vein, either temporarily or for longterm treatment.

Purpose
Patients who cannot consume enough nutrients or
who cannot eat at all due to an illness, surgery, or
accident, can be fed through an intravenous (IV) line
or tube. An IV can be used for as little as a few hours, to
provide fluids to a patient during a short surgical procedure, or to rehydrate a patient after a viral illness.
GALE ENCYCLOPEDIA OF MEDICINE

Patients with more serious and long term illnesses
and conditions may require months or even years of
intravenous therapy to meet their nutritional needs.
These patients may require a central venous access
port. A specialized catheter (Silastic Broviac or
Hickman) is inserted beneath the skin and positioned
below the collarbone. Fluids can then be injected
directly into the bloodstream for long periods of
time. X rays are taken to ensure that the permanent
catheter is properly positioned.

Precautions
Patients receiving IV therapy need to be monitored to ensure that the IV solutions are providing
the correct amounts of fluids, minerals, and other
nutrients needed.

Description
There are two types of IV, or parenteral, nutrition.
Parenteral nutrition is that which is delivered through
a system other than the digestive system. In this case,
the nutrition is delivered through a vein. Partial parenteral nutrition (PPN) is given for short periods of
time, to replace some of the nutrients required daily
and only supplements a normal diet. Total parenteral
nutrition (TPN) is given to someone who cannot eat
anything and must receive all nutrients required daily
through an intravenous line. Both of these types of
nutrition can be performed in a medical facility or at
the patient’s home. Home parenteral nutrition (HPN)
usually requires a central venous catheter, which must
first be inserted in a fully equiped medical facility.
After it is inserted, therapy can continue at home.
Basic IV solutions are sterile water with small
amounts of sodium (salt) or dextrose (sugar) supplied
in bottles or thick plastic bags that can hang on a stand
mounted next to the patient’s bed. Additional minerals, like potassium and calcium, vitamins, or drugs can
be added to the IV solution by injecting them into the
bottle or bag with a needle. These simple sugar and salt
solutions can provide fluids, calories, and electrolytes
necessary for short periods of time. If a patient
requires intravenous feeding for more than a few
days, additional nutrients like proteins and fats will
be included. The amounts of each of the nutrients to be
added will depend on the patient’s age, medical condition, and particular nutritional requirements.

Preparation
A doctor orders the IV solution and any additional nutrients or drugs to be added to it. The doctor
2647

Nutrition through an intravenous line

Resources

Nutritional supplements

KEY TERMS
Home parenteral nutrition (HPN)—Long-term parenteral nutrition, given through a central venous
catheter and administered in the patient’s home.
Intravenous—Into a vein; a needle is inserted into a
vein in the back of the hand, inside the elbow, or
some other location on the body. Fluids, nutrients,
and drugs can be injected.
Parenteral—Not in or through the digestive system.
Parenteral nutrition is given through the veins of the
circulatory system, rather than through the digestive system.
Partial parenteral nutrition (PPN)—A solution,
containing some essentail nutrients, is injected
into a vein to supplement other means of nutrition,
usually a partially normal diet of food.
Total parenteral nutrition (TPN)—A solution containing all the required nutrients including protein,
fat, calories, vitamins, and minerals, is injected
over the course of several hours, into a vein. TPN
provides a complete and balanced source of nutrients for patients who cannot consume a normal
diet.

When using HPN, the catheter should be kept clean
at all times. The dressings around the site should be
changed at least once a week and the catheter site should
be monitored closely for signs of redness, swelling, and
drainage. The patient’s extremities should be watched
for swelling, which is a sign of nutritional imbalance.

Risks
There is a risk of infection at the injection site, and
for patients on long term IV therapy, the risk of an
infection spreading to the entire body is fairly high. It
is possible that the IV solution may not provide all of the
nutrients needed, leading to a deficiency or an imbalance. If the needle becomes dislodged, it is possible that
the solution may flow into tissues around the injection
site rather than into the vein. The patient should be
monitored regularly, particulary if receiving HPN, as
intravenous nutrition can potentially cause infection at
the site of the catheter, high blood sugar, and low blood
potassium, which can all be life-threatening.
Resources
OTHER

‘‘Clinical Management: Parenteral Nutrition’’ In Revised
Intravenous Nursing Standards of Practice. <http://
www.ins1.org>.

Altha Roberts Edgren
also specifies the rate at which the IV will be infused.
The IV solutions are prepared under the supervision
of a doctor, pharmacist, or nurse, using sanitary
techniques that prevent bacterial contamination.
Just like a prescription, the IV is clearly labeled to
show its contents and the amounts of any additives.
The skin around the area where the needle is inserted
is cleaned and sanitized. Once the needle is in place, it
will be taped to the skin to prevent it from
dislodging.
In the case of HPN, the IV solution is delivered to
the patient’s home on a regular basis and should be
kept refrigerated. Each bag will have an expiration
date, by which time the bag should be used. The solution should be allowed to be warmed to room temperature before intravenous nutrition begins.

Aftercare
Patients who have been on IV therapy for more
than a few days may need to have foods reintroduced
gradually to give the digestive tract time to start working again. After the IV needle is removed, the site should
be inspected for any signs of bleeding or infection.
2648

Nutritional supplements
Definition
Nutritional supplements include vitamins, minerals, herbs, meal supplements, sports nutrition products, natural food supplements, and other related
products used to boost the nutritional content of the
diet.

Purpose
Nutritional supplements are used for many purposes. They can be added to the diet to boost overall
health and energy; to provide immune system support
and reduce the risks of illness and age-related conditions; to improve performance in athletic and mental
activities; and to support the healing process during
illness and disease. However, most of these products
are treated as food and not regulated as drugs are.
GALE ENCYCLOPEDIA OF MEDICINE

The Natural Nutritional Foods Association estimated that in 2003 nutritional supplements amounted
to a $19.8 billion market in the United States. By
category, vitamins provided $6.6 billion in sales,
herbs $4.2 billion, meal supplements $2.5 billion,
sports nutrition products $2.0 billion, minerals $1.8
billion, and specialty and other products totaling $2.7
billion. The nutritional supplement industry provides
a huge array of products for consumer needs.
Vitamins
Vitamins are micronutrients, or substances that
the body uses in small amounts, as compared to
macronutrients, which are the proteins, fats, and carbohydrates that make up all food. Vitamins are present in food, but adequate quantities of vitamins may
be reduced when food is overcooked, processed, or
improperly stored. For instance, processing whole
wheat grain into white flour reduces the contents of
vitamins B and E, fiber, and minerals, including zinc
and iron. The body requires vitamins to support its
basic biochemical functions, and deficiencies over time
can lead to illness and disease.
Vitamins are either water-soluble or fat-soluble.
Water-soluble vitamins dissolve in water and pass
through the body quickly, meaning that the body
needs them on a regular basis. Water-soluble vitamins
include the B-complex vitamins and vitamin C. Fatsoluble vitamins are stored in the body’s fatty tissue,
meaning that they remain in the body longer. Fatsoluble vitamins include vitamins A, D, E, and K.
The amount of vitamins needed by the body has
been the subject of much research. The U.S. government has published recommended dietary allowances
(RDAs) for each vitamin for the general population.
These figures can be used as guidelines, but individuals
may have different needs depending on gender, age,
and health conditions.
Vitamins can be natural or synthetic. Natural
vitamins are extracted from food sources, while synthetic vitamins are formulated in laboratory processes.
The only vitamin for which there is a noted difference
between the natural and synthetic forms is vitamin E.
The natural form is labeled d-alpha-tocopherol while
the synthetic form is named dl-alpha-tocopherol, with
the extra ‘‘l’’ signifying laboratory production.
Natural vitamin E has been shown to be slightly
more absorbable by the body than the synthetic version, although for other vitamins no significant differences in absorption have been noted.
GALE ENCYCLOPEDIA OF MEDICINE

Minerals
Minerals are micronutrients and are essential for
the proper functioning of the body. Cells in the body
require minerals as part of their basic make-up and
chemical balance, and minerals are present in all
foods. Minerals can either be bulk minerals, used by
the body in larger quantities, or trace minerals, used
by the body in minute or trace amounts. Bulk minerals
include sodium, potassium, calcium, magnesium, and
phosphorus. Trace minerals include iron, zinc, selenium, iodine, chromium, copper, manganese, and
others. Some studies have shown that the amount of
minerals, particularly trace minerals, may be decreasing in foods due to mineral depletion of the soil caused
by unsustainable farming practices and soil erosion.
Supplemental minerals are available in chelated form,
in which they are bonded to proteins in order to
improve their absorption by the body.
Herbs
Herbal supplements are added to the diet for both
nutritional and medicinal purposes. Herbs have been
used for centuries in many traditional medicine systems, and as sources of phytochemicals, or substances
found in plants that have notable effects in the body.
Chinese medicine and Ayurvedic medicine from India,
two of the world’s oldest healing systems, use hundreds of herbal medications. Naturopathy and
homeopathy, two other systems of natural healing,
also rely on herbal preparations as their main sources
of medication. The medicinal effects of herbs are getting scientific validation; about one-fourth of all pharmaceuticals have been derived directly from plant
sources, including aspirin (found in willow bark),
codeine (from poppy seeds), paclitaxel (Taxol), a
patented drug for ovarian and breast cancer (from
the Pacific Yew tree), and many others.
Herbs can supplement the diet to aid in overall
health or to stimulate healing for specific conditions.
For instance, ginseng is used as a general tonic to
increase overall health and vitality, while echinacea is
a popular herb used to stimulate the body’s resistance
to colds and infections. Herbs come in many forms.
They can be purchased as capsules and tablets, as well
as in tinctures, teas, syrups, and ointments.
Meal supplements
Meal supplements are used to replace or fortify
meals. They may be designed for people with special
needs, or for people with illnesses that may affect
digestion capabilities and nutritional requirements.
Meal supplements may contain specific blends of
2649

Nutritional supplements

Description

Nutritional supplements

macronutrients, or proteins, carbohydrates, fats, and
fiber. Some meal supplements consist of raw, unprocessed foods, or vegetarian or vegan options, or high
protein and low fat composition. Meal supplements
are available to support some popular diet programs.
Meal supplements are often fortified with vitamins,
minerals, herbs, and nutrient-dense foods.
Sports nutrition
Nutritional supplements may be designed to provide specialized support for athletes. Some of these
consist of high-protein products, such as amino acid
supplements, while other products contain nutrients
that support metabolism, energy, and athletic performance and recovery. People engaging in intense
athletic activity may have increased needs for watersoluble vitamins, antioxidants, and certain minerals,
including chromium. Sports drinks contain blends of
electrolytes (salts) that the body loses during exertion
and sweating, as well as vitamins, minerals, and performance-supporting herbs.
Other nutritional supplements
Other nutritional supplements include nutrientdense food products. Examples of these are brewer’s
yeast, spirulina (sea algea), bee pollen and royal jelly,
fish oil and essential fatty acid supplements, colostrum
(a specialty dairy product), psyllium seed husks (a
source of fiber), wheat germ, wheatgrass, and medicinal mushrooms such as the shiitake and reishi
varieties.
Specialty products may offer particular health
benefits or are targeted for specific conditions. These
products may consist of whole foods or may be isolated compounds from natural or synthetic sources.
Examples include antioxidants, probiotics (supplements containing friendly bacteria for the digestive
tract), digestive enzymes, shark cartilage, or other
animal products, or chemical extracts such as the hormone DHEA (dehydroepiandrosterone) and coenzyme Q10, an antioxidant.
General guidelines
Considering average dietary needs and the prevalence of certain health conditions, some basic guidelines may provide the foundation for the effective use
of nutritional supplements. First, a high quality,
broad-spectrum multivitamin and mineral supplement, taken once per day, is recommended to provide
a range of nutrients. This should contain the B-complex vitamins B6, B12, and folic acid, which may help
prevent heart disease, and the minerals zinc and
2650

copper, which aid immunity. In addition to a multivitamin, antioxidants can be added to a supplementation
routine. These include vitamin A (or beta-carotene),
vitamin C, and vitamin E, and the mineral selenium.
Antioxidants may have several positive effects on the
body, such as slowing the aging process, reducing
the risks of cancer and heart disease, and reducing
the risks of illness and infection by supporting the
immune system. Coenzyme Q10 is another antioxidant in wide usage, as studies have shown it may
improve the health of the heart and reduce the effects
of heart disease. Essential fatty acids, particularly
omega-3, are also recommended as they are involved
in many important processes in the body, including
brain function. Calcium supplementation is recommended for the elderly and for women, to strengthen
bones and prevent bone loss. Calcium supplements
that are balanced with magnesium have a less constipating effect and are better absorbed.
After basic nutritional requirements are supported, supplements may be used to target specific
needs and health conditions. For instance, athletes,
men, women, children, the elderly, and vegetarians
have differing needs for nutrients, and an informed
use of supplements would take these differences into
account. People suffering from health conditions and
diseases may use specific supplements to target their
condition and to support the body’s healing capacity
by providing optimal amounts of nutrients.

Recommended dosage
Dosages of nutritional supplements vary widely,
depending on the product and individual needs. For
vitamins and minerals, U.S. RDA’s are essential
guidelines. For other products, manufacturers’ guidelines, consumer information sources such as nutritional books and magazines, and practitioners
including nutritionists and naturopathic physicians
may be consulted.

Precautions
Overall diet is an important first consideration for
those considering nutritional supplementation.
Healthy dietary habits can help optimize nutrition
and the absorption of supplements, and nutritional
supplements cannot substitute for a diet that is not
nutritionally balanced in the first place. Supplements
are best used moderately to supply any extra nutritional requirements. Sound diets contain a variety of
wholesome foods. At least five servings per day of
fruits and vegetables are recommended, as well as the
inclusion of whole grains in the diet. Variety in the diet
GALE ENCYCLOPEDIA OF MEDICINE

Generally, nutrients from food sources are more
efficiently utilized by the body than isolated substances. For instance, fresh fruit and vegetable juice
could be used to provide concentrated amounts of
particular nutrients, such as vitamins A and C, to the
diet. As another example, eating plenty of leafy green
vegetables is a healthy option for those wishing to add
calcium to the diet.
Vitamins and minerals are most easily digested
with food. Fat-soluble vitamins should be taken with
food that contains fat. Vitamins tend to work synergistically, meaning that they work together in order
to be effective. For instance, vitamin E requires some
of the B-complex vitamins and the minerals selenium
and zinc for most effective absorption. Some minerals may not be absorbed or may inhibit each other
when taken in improper ratios. Generally, a high
quality, broad-spectrum vitamin and mineral supplement will be formulated to prevent unfavorable
interactions.
Vitamin A can become toxic when taken in large
amounts (over 100,000 International Units) on a daily
basis over time, as can vitamin D. Substituting betacarotene for vitamin A can alleviate this risk. Very
large doses of minerals taken over long periods may
have toxic effects in the body. Dosages far exceeding
RDA’s of vitamins are not recommended, nor are
large doses of other supplements.
Consumers can make wise choices for nutritional
supplementation by consulting professional nutritionists and naturopathic physicians. Nutritional supplements are best added into the diet slowly, starting with
small dosages and working up to the manufacturers’
recommended amounts over time. Also, some supplements, such as herbal medications that may stimulate
processes in the body, are best taken intermittently,
allowing the body occasional rest periods without the
supplement. To avoid unfavorable interactions, nutritional supplements are best used moderately and individually, rather than taking handfuls of capsules and
tablets for various needs and conditions at the same
time. Finally, consumers should be wary of excessive
or grandiose health claims made by manufacturers of
nutritional supplements and rely on scientific information to validate these claims.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Antioxidants—A class of biochemicals that have
been found to protect cells from free-radical
damage.
Enzymes—Chemical catalysts that help initiate
biochemical processes.
Essential fatty acids—Sources of fat in the diet,
including omega-3 and omega-6 fatty acids.
Naturopathic physicians—Physicians specializing
in the treatment of disease using a variety of natural
methods and plant-based medicines.

Side effects
Some nutritional supplements can cause upset
stomach and allergic reactions, including rashes, flushing, nausea, sweating, and headaches.

Interactions
Herbal preparations and nutritional supplements
may interact unfavorably with pharmaceutical drugs.
For instance, some nutritional supplements recommended for nervous system function may not be
recommended for those taking pharmaceutical antidepressants, such as taking 5-HTP, a nutritional supplement for the brain, or the herb St. John’s Wort,
with prescription antidepressants. Vitamin C should
not be taken with aspirin, as it can irritate the stomach
and limit absorption. Minerals should be taken in
proper proportions to prevent unfavorable interactions; large amounts of zinc may deplete the body of
the mineral copper, while too much calcium adversely
affects the magnesium levels in the body. Balanced
mineral supplements are recommended to alleviate
these interactions.
Resources
BOOKS

Balch, Phyllis A. Prescription for Nutritional Healing. East
Rutherford, NJ: Penguin Group Inc., 2005.
Firshein, Richard. The Nutraceutical Revolution: 20 CuttingEdge Nutrients to Help You Design Your Own Perfect
Whole-Life Program. East Rutherford, NJ: Penguin
Group Inc., 1999.
Hudson, Tori. Women’s Encyclopedia of Natural Medicine.
New York: McGraw-Hill, 1999.
Weil, Andrew. Eating Well for Optimum Health: The
Essential Guide to Bringing Health and Pleasure Back to
Eating. New York: Harper Trade, 2001.
2651

Nutritional supplements

is important to provide a full range of vitamins and
minerals. Overeating inhibits digestion and absorption of nutrients, while regular exercise contributes
to sound nutrition, by improving metabolism and
digestion. Drinking plenty of clean water prevents
dehydration, improves digestion, and helps the body
flush out impurities.

Nystagmus

PERIODICALS

Natural Health http://www.naturalhealthmag.com.
ORGANIZATIONS

Center for Science in the Public Interest. 1875 Connecticut
Avenue NW, Suite 300, Washington, D.C. 20009.
(202)332-9110. <http://www.cspinet.org>. Publishes
Nutrition Action Newsletter.
National Nutritional Foods Association. 1220 19th Street
NW, Washington, D.C. 20036. (202)223-0101. <http://
www.nnfa.org>.
OTHER

USDA Food and Nutrition Information Center. <http://
www.nal.usda.gov/fnic>.

Douglas Dupler

Nystagmus
Definition
Rhythmic, oscillating motions of the eyes are
called nystagmus. The to-and-fro motion is generally
involuntary. Vertical nystagmus occurs much less frequently than horizontal nystagmus and is often, but
not necessarily, a sign of serious brain damage.
Nystagmus can be a normal physiological response
or a result of a pathologic problem.

Description
The eyes play a critical role in maintaining balance. They are directly connected to other organs of
equilibrium, most important of which is the inner ear.
Paired structures called the semicircular canals deep in
the skull behind the ears sense motion and relay that
information to balance control centers in the brain.
The eyes send visual information to the same centers.
A third set of sensors consists of nerve endings all over
the body, particularly in joints, that detect position.
All this information is integrated to allow the body to
navigate in space and gravity.
It is possible to fool this system or to overload it
with information so that it malfunctions. A spinning
ride at the amusement park is a good way to overload
it with information. The system has adapted to the
spinning, expects it to go on forever, and carries that
momentum for some time after it is over. Nystagmus is
the lingering adjustment of the eyes to tracking the
world as it revolves around them.
2652

Nystagmus can be classified depending upon the
type of motion of the eyes. In pendular nystagmus the
speed of motion of the eyes is the same in both directions. In jerk nystagmus there is a slow and fast phase.
The eyes move slowly in one direction and then seem
to jerk back in the other direction.
Nystagmus can be present at birth (congenital) or
acquired later on in life. A certain type of acquired
nystagmus, called spasmus nutans, includes a head tilt
and head bobbing and generally occurs between four
to 12 months of age. It may last a few months to a few
years, but generally goes away by itself.
Railway nystagmus is a physiological type of nystagmus. It happens when someone is on a moving train
(thus the term railway) and is watching a stationary
object which appears to be going by. The eyes slowly
follow the object and then quickly jerk back to start
over. Railway nystagmus (also called optokinetic nystagmus) is a type of jerk nystagmus. This phenomenon
can be used to check vision in infants. Nystagmus can
also be induced by fooling the semicircular canals.
Caloric stimulation refers to a medical method of
testing their connections to the brain, and therefore
to the eyes. Cold or warm water flushed into the ear
canal will generate motion signals from the inner ear.
The eyes will respond to this signal with nystagmus if
the pathways are intact.

Causes and symptoms
There are many causes of nystagmus. Nystagmus
may be present at birth. It may be a result of the lack of
development of normal binocular fixation early on in
life. This can occur if there is a cataract at birth or a
problem is some other part of the visual system. Some
other conditions that nystagmus may be associated
with include:


Albinism. This condition is caused by a decrease in
pigmentation and may affect the eyes.



Disorders of the eyes. This may include optic atrophy, color blindness, very high nearsightedness
(myopia) or severe astigmatism, or opacities in the
structures of the eyes.



Acute labyrinthitis. This is an inflammation in the
inner ear. The patient may have dizziness (vertigo),
nausea and vomiting, and nystagmus.



Brain lesions. Disease in many parts of the brain can
result in nystagmus.



Alcohol and drugs. Alcohol and some medications
(e.g., anti-epilepsy medications) can induce or exaggerate nystagmus.
GALE ENCYCLOPEDIA OF MEDICINE

Multiple sclerosis. A disease of the central nervous
system.

Diagnosis
Nystagmus is a sign, not a disease. If abnormal, it
indicates a problem in one of the systems controlling
it. An ophthalmologist and/or neuro-ophthalmologist
should be consulted.

Treatment
There is one kind of nystagmus that seems to
occur harmlessly by itself. The condition, benign
positional vertigo, produces vertigo and nystagmus
when the head is moved in certain directions. It can
arise spontaneously or after a concussion. Motion
sickness medicines sometimes help. But the reaction
will dissipate if continuously evoked. Each morning a
patient is asked to produce the symptom by moving

GALE ENCYCLOPEDIA OF MEDICINE

his or her head around until it no longer happens.
This prevents it from returning for several hours or
the entire day.
Prisms, contact lenses, eyeglasses, or eye muscle
surgery are some possible treatments. These therapies
may reduce the nystagmus but may not alleviate it.
Again, because nystagmus may be a symptom, it is
important to determine the cause.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.

J. Ricker Polsdorfer, MD

2653

Nystagmus



O
Obesity
Definition
Obesity is an abnormal accumulation of body fat,
usually 20% or more over an individual’s ideal body
weight. Obesity is associated with increased risk of
illness, disability, and death.
The branch of medicine that deals with the study
and treatment of obesity is known as bariatrics.
As obesity has become a major health problem in
the United States, bariatrics has become a separate
medical and surgical specialty.

Description
Obesity traditionally has been defined as a weight
at least 20% above the weight corresponding to the
lowest death rate for individuals of a specific height,
gender, and age (ideal weight). Twenty to forty percent
over ideal weight is considered mildly obese; 40–100%
over ideal weight is considered moderately obese;
and 100% over ideal weight is considered severely, or
morbidly, obese. More recent guidelines for obesity
use a measurement called BMI (body mass index)
which is the individual’s weight multiplied by 703
and then divided by twice the height in inches. BMI
of 25.9–29 is considered overweight; BMI over 30 is
considered obese. Measurements and comparisons of
waist and hip circumference can also provide some
information regarding risk factors associated with
weight. The higher the ratio, the greater the chance
for weight-associated complications. Calipers can be
used to measure skin-fold thickness to determine
whether tissue is muscle (lean) or adipose tissue (fat).
Much concern has been generated about the
increasing incidence of obesity among Americans.
Some studies have noted an increase from 12% to
18% occurring between 1991 and 1998. Other studies
have actually estimated that a full 50% of all
GALE ENCYCLOPEDIA OF MEDICINE

Americans are overweight. The World Health
Organization terms obesity a worldwide epidemic,
and the diseases which can occur due to obesity are
becoming increasingly prevalent.
Excessive weight can result in many serious,
potentially life-threatening health problems, including
hypertension, Type II diabetes mellitus (non-insulin
dependent diabetes), increased risk for coronary
disease, increased unexplained heart attack, hyperlipidemia, infertility, and a higher prevalence of colon,
prostate, endometrial, and, possibly, breast cancer.
Approximately 300,000 deaths a year are attributed
to obesity, prompting leaders in public health, such as
former Surgeon General C. Everett Koop, M.D., to
label obesity ‘‘the second leading cause of preventable
deaths in the United States.’’

Causes and symptoms
The mechanism for excessive weight gain is
clear—more calories are consumed than the body
burns, and the excess calories are stored as fat
(adipose) tissue. However, the exact cause is not as
clear and likely arises from a complex combination of
factors. Genetic factors significantly influence how the
body regulates the appetite and the rate at which it
turns food into energy (metabolic rate). Studies of
adoptees confirm this relationship—the majority of
adoptees followed a pattern of weight gain that more
closely resembled that of their birth parents than their
adoptive parents. A genetic predisposition to weight
gain, however, does not automatically mean that a
person will be obese. Eating habits and patterns of
physical activity also play a significant role in the
amount of weight a person gains. Recent studies
have indicated that the amount of fat in a person’s
diet may have a greater impact on weight than the
number of calories it contains. Carbohydrates like
cereals, breads, fruits, and vegetables and protein
(fish, lean meat, turkey breast, skim milk) are
converted to fuel almost as soon as they are consumed.
2655

Obesity

Height And Weight Goals

Men
Height
5’2’’ 5’3’’ 5’4’’
5’5’’ 5’6’’ 5’7’’
5’8’’ 5’9’’ 5’10’’
5’11’’ 6’0’’ 6’1’’
6’2’’ 6’3’’ 6’4’’

Small Frame
128–134 lbs. 130–136 132–138
134–140 136–142 138–145
140–148 142–151 144–154
146–157 159–160 152–164
155–168 158–172 162–176

Medium Frame
131–141 lbs. 133–143 135–145
137–148 139–151 142–154
145–157 148–160 151–163
154–166 157–170 160–174
164–178 167–182 171–187

Large Frame
138–150 lbs. 140–153 142–153
144–160 146–164 149–168
152–172 155–176 158–180
161–184 164–188 168–192
172–197 176–202 181–207

Small Frame
102–111 lbs. 103–113 104–115
106–118 108–121 111–124
114–127 117–130 120–133
123–136 126–139 129–142
132–145 135–148 138–151

Medium Frame
109–121 lbs. 111–123 113–126
115–129 118–132 121–135
124–141 127–141 130–144
133–147 136–150 139–153
142–156 145–159 148–162

Large Frame
118–131 lbs. 120–134 112–137
125–140 128–143 131–147
137–151 137–155 140–159
143–163 146–167 149–170
152–176 155–176 158–179

Women
Height
4’10’’ 4’11’’ 5’0’’
5’1’’ 5’2’’ 5’3’’
5’4’’ 5’5’’ 5’6’’
5’7’’ 5’8’’ 5’9’’
5’10’’ 5’11’’ 6’0’’

Most fat calories are immediately stored in fat cells,
which add to the body’s weight and girth as they
expand and multiply. A sedentary lifestyle, particularly
prevalent in affluent societies, such as in the United
States, can contribute to weight gain. Psychological
factors, such as depression and low self-esteem may,
in some cases, also play a role in weight gain.
At what stage of life a person becomes obese can
affect his or her ability to lose weight. In childhood,
excess calories are converted into new fat cells
(hyperplastic obesity), while excess calories consumed
in adulthood only serve to expand existing fat cells
(hypertrophic obesity). Since dieting and exercise can
only reduce the size of fat cells, not eliminate them,
persons who were obese as children can have great
difficulty losing weight, since they may have up to
five times as many fat cells as someone who became
overweight as an adult.
Obesity can also be a side effect of certain disorders and conditions, including:


Cushing’s syndrome, a disorder involving the excessive release of the hormone cortisol



hypothyroidism, a condition caused by an underactive thyroid gland



neurologic disturbances, such as damage to the
hypothalamus, a structure located deep within the
brain that helps regulate appetite



consumption of such drugs as steroids, antipsychotic
medications, or antidepressants

The major symptoms of obesity are excessive
weight gain and the presence of large amounts of fatty
tissue. Obesity can also give rise to several secondary
conditions, including:
2656



arthritis and other orthopedic problems, such as
lower back pain



hernias



heartburn



adult-onset asthma



gum disease



high cholesterol levels



gallstones



high blood pressure



menstrual irregularities or cessation of menstruation
(amenorhhea)



decreased fertility, and pregnancy complications



shortness of breath that can be incapacitating



sleep apnea and sleeping disorders



skin disorders arising from the bacterial breakdown
of sweat and cellular material in thick folds of skin or
from increased friction between folds



emotional and social problems

Diagnosis
Diagnosis of obesity is made by observation and
by comparing the patient’s weight to ideal weight
charts. Many doctors and obesity researchers refer
to the body mass index (BMI), which uses a heightweight relationship to calculate an individual’s ideal
weight and personal risk of developing obesity-related
health problems. Physicians may also obtain direct
measurements of an individual’s body fat content by
using calipers to measure skin-fold thickness at the
back of the upper arm and other sites. The most
GALE ENCYCLOPEDIA OF MEDICINE

Doctors may also note how a person carries excess
weight on his or her body. Studies have shown that this
factor may indicate whether or not an individual has
a predisposition to develop certain diseases or conditions that may accompany obesity. ‘‘Apple-shaped’’
individuals who store most of their weight around
the waist and abdomen are at greater risk for cancer,
heart disease, stroke, and diabetes than ‘‘pear-shaped’’
people whose extra pounds settle primarily in their
hips and thighs.

Treatment
Treatment of obesity depends primarily on how
overweight a person is and his or her overall health.
However, to be successful, any treatment must affect
life-long behavioral changes rather than short-term
weight loss. ‘‘Yo-yo’’ dieting, in which weight is repeatedly lost and regained, has been shown to increase a
person’s likelihood of developing fatal health problems
than if the weight had been lost gradually or not lost at
all. Behavior-focused treatment should concentrate on:






What and how much a person eats. This aspect may
involve keeping a food diary and developing a better
understanding of the nutritional value and fat content of foods. It may also involve changing groceryshopping habits (e.g., buying only what is on a
prepared list and only going on a certain day), timing
of meals (to prevent feelings of hunger, a person may
plan frequent, small meals), and actually slowing
down the rate at which a person eats.
How a person responds to food. This may involve
understanding what psychological issues underlie a
person’s eating habits. For example, one person may
binge eat when under stress, while another may
always use food as a reward. In recognizing these
psychological triggers, an individual can develop
alternate coping mechanisms that do not focus on
food.
How they spend their time. Making activity and
exercise an integrated part of everyday life is a key
to achieving and maintaining weight loss. Starting
slowly and building endurance keeps individuals
from becoming discouraged. Varying routines and
trying new activities also keeps interest high.

GALE ENCYCLOPEDIA OF MEDICINE

For most individuals who are mildly obese, these
behavior modifications entail life-style changes they
can make independently while being supervised by
a family physician. Other mildly obese persons may
seek the help of a commercial weight-loss program
(e.g., Weight Watchers). The effectiveness of these
programs is difficult to assess, since programs vary
widely, drop-out rates are high, and few employ members of the medical community. However, programs
that emphasize realistic goals, gradual progress,
sensible eating, and exercise can be very helpful and
are recommended by many doctors. Programs that
promise instant weight loss or feature severely
restricted diets are not effective and, in some cases,
can be dangerous.
For individuals who are moderately obese, medically supervised behavior modification and weight
loss are required. While doctors will put most moderately obese patients on a balanced, low-calorie diet
(1200–1500 calories a day), they may recommend
that certain individuals follow a very-low-calorie
liquid protein diet (400–700 calories) for as long as
three months. This therapy, however, should not be
confused with commercial liquid protein diets or commercial weight-loss shakes and drinks. Doctors tailor
these diets to specific patients, monitor patients carefully, and use them for only a short period of time. In
addition to reducing the amount and type of calories
consumed by the patient, doctors will recommend
professional therapists or psychiatrists who can help
the individual effectively change his or her behavior in
regard to eating.
For individuals who are severely obese, dietary
changes and behavior modification may be accompanied by surgery to reduce or bypass portions of the
stomach or small intestine. Although obesity surgery is
less risky as of 2003 because of recent innovations in
equipment and surgical technique, it is still performed
only on patients for whom other strategies have failed
and whose obesity seriously threatens their health.
Other surgical procedures are not recommended,
including liposuction, a purely cosmetic procedure in
which a suction device is used to remove fat from
beneath the skin, and jaw wiring, which can damage
gums and teeth and cause painful muscle spasms.
Appetite-suppressant drugs are sometimes prescribed to aid in weight loss. These drugs work by
increasing levels of serotonin or catecholamine, which
are brain chemicals that control feelings of fullness.
Appetite suppressants, though, are not considered
truly effective, since most of the weight lost while
taking them is usually regained after stopping them.
Also, suppressants containing amphetamines can be
2657

Obesity

accurate means of measuring body fat content
involves immersing a person in water and measuring
relative displacement; however, this method is very
impractical and is usually only used in scientific
studies requiring very specific assessments. Women
whose body fat exceeds 30% and men whose body
fat exceeds 25% are generally considered obese.

Obesity

200

2.05
6'8"
2.00

440
420

180

45

400
380

6'7"
160

360
340

6'6"

320
1.95

1.90

6'5"

140

6'4"

130

6'3"

120

6'2"

110

6'1"

100

40

310
300
290

280
270

260

35

250

240
230

1.85

220
210

6'00"
90
1.80

5'11"
5'10"

85
80
75

1.75

1.70

5'9"

1.65

65

5'7"

60

5'5"
5'4"

1.60

5'3"

190

180
170
160

70

5'8"

5'6"

30
29
28
27
26
25
24
23

200

55

150
140

22

135

21

130
125

20

120
115

50

19

110

18

105

45

100

17

95

40

90

5'2"
1.55

5'1"
5'0"

HEIGHT

WEIGHT

(cm)

(kg)

(in)

(lbs)

BMI
(kg/m2)

Body/mass index can be calculated by locating your height and weight on the chart and drawing a diagonal line between the two.
Where the line crosses over the third bar is the approximate BMI. (Illustration by Argosy Inc.)

2658

GALE ENCYCLOPEDIA OF MEDICINE

Other weight-loss medications available with a
doctor’s prescription include:

currently being developed or tested include ones that
can prevent fat absorption or digestion; reduce the
desire for food and prompt the body to burn calories
more quickly; and regulate the activity of substances
that control eating habits and stimulate overeating.

Alternative treatment
The Chinese herb ephedra (Ephedra sinica),
combined with caffeine, exercise, and a low-fat diet in
physician-supervised weight-loss programs, can cause
at least a temporary increase in weight loss. However,
the large doses of ephedra required to achieve the
desired result can also cause:


anxiety



heart arrhythmias



heart attack



diethylpropion (Tenuate, Tenuate dospan)



high blood pressure



mazindol (Mazanor, Sanorex)



insomnia



phendimetrazine (Bontril, Plegine, Prelu-2, X-Trozine)



irritability



phentermine (Adipex-P, Fastin, Ionamin, Oby-trim)



nervousness

Phenylpropanolamine (Acutrim, Dextarim) is the
only nonprescription weight-loss drug approved by
the FDA These over-the-counter diet aids can boost
weight loss by 5%. Combined with diet and exercise
and used only with a doctor’s approval, prescription
anti-obesity medications enable some patients to lose
10% more weight than they otherwise would. Most
patients regain lost weight after discontinuing use of
either prescription medications or nonprescription
weight-loss products.



seizures



strokes



death

Prescription medications or over-the-counter
weight-loss products can cause:


constipation



dry mouth



headache



irritability



nausea



nervousness



sweating

None of them should be used by patients taking
monoamine oxidase inhibitors (MAO inhibitors).
Doctors sometimes prescribe fluoxetine (Prozac),
an antidepressant that can increase weight loss by
about 10%. Weight loss may be temporary and side
effects of this medication include diarrhea, fatigue,
insomnia, nausea, and thirst. Weight-loss drugs
GALE ENCYCLOPEDIA OF MEDICINE

Ephedra should not be used by anyone with a
history of diabetes, heart disease, or thyroid problems.
In fact, an article that appeared in the Journal of the
American Medical Association in early 2003 advised
against the use of ephedra.
Diuretic herbs, which increase urine production,
can cause short-term weight loss but cannot help
patients achieve lasting weight control. The body
responds to heightened urine output by increasing
thirst to replace lost fluids, and patients who use
diuretics for an extended period of time eventually
start retaining water again anyway. In moderate
doses, psyllium, a mucilaginous herb available in
bulk-forming laxatives like Metamucil, absorbs fluid
and makes patients feel as if they have eaten enough.
Red peppers and mustard help patients lose weight
more quickly by accelerating the metabolic rate.
They also make people more thirsty, so they crave
water instead of food. Walnuts contain serotonin,
the brain chemical that tells the body it has eaten
enough. Dandelion (Taraxacum officinale) can raise
metabolism and counter a desire for sugary foods.
Acupressure and acupuncture can also suppress
food cravings. Visualization and meditation can create
and reinforce a positive self-image that enhances the
2659

Obesity

potentially abused by patients. While most of the
immediate side-effects of these drugs are harmless, the
long-term effects of these drugs, in many cases, are
unknown. Two drugs, dexfenfluramine hydrochloride
(Redux) and fenfluramine (Pondimin) as well as a combination fenfluramine-phentermine (Fen/Phen) drug,
were taken off the market when they were shown to
cause potentially fatal heart defects. In November 1997,
the United States Food and Drug Administration
(FDA) approved a new weight-loss drug, sibutramine
(Meridia). Available only with a doctor’s prescription,
Meridia can significantly elevate blood pressure and
cause dry mouth, headache, constipation, and insomnia.
This medication should not be used by patients with a
history of congestive heart failure, heart disease, stroke,
or uncontrolled high blood pressure.

Obesity

patient’s determination to lose weight. By improving
physical strength, mental concentration, and emotional
serenity, yoga can provide the same benefits. Also,
patients who play soft, slow music during meals often
find that they eat less food but enjoy it more.
Getting the correct ratios of protein, carbohydrates, and good-quality fats can help in weight
loss via enhancement of the metabolism. Support
groups that are informed about healthy, nutritious,
and balanced diets can offer an individual the support
he or she needs to maintain this type of eating regimen.

Prognosis
As many as 85% of dieters who do not exercise
on a regular basis regain their lost weight within two
years. In five years, the figure rises to 90%. Repeatedly
losing and regaining weight (yo yo dieting) encourages
the body to store fat and may increase a patient’s risk
of developing heart disease. The primary factor in
achieving and maintaining weight loss is a life-long
commitment to regular exercise and sensible eating
habits.

Prevention
Obesity experts suggest that a key to preventing
excess weight gain is monitoring fat consumption
rather than counting calories, and the National
Cholesterol Education Program maintains that only
30% of calories should be derived from fat. Only onethird of those calories should be contained in saturated fats (the kind of fat found in high concentrations
in meat, poultry, and dairy products). Because most
people eat more than they think they do, keeping a
detailed food diary is a useful way to assess eating
habits. Eating three balanced, moderate-portion
meals a day—with the main meal at mid-day—is a
more effective way to prevent obesity than fasting or
crash diets. Exercise increases the metabolic rate by
creating muscle, which burns more calories than fat.
When regular exercise is combined with regular,
healthful meals, calories continue to burn at an accelerated rate for several hours. Finally, encouraging
healthful habits in children is a key to preventing
childhood obesity and the health problems that follow
in adulthood.

New directions in obesity treatment
The rapid rise in the incidence of obesity in the
United States since 1990 has prompted researchers to
look for new treatments. One approach involves the
application of antidiabetes drugs to the treatment of
2660

KEY TERMS
Adipose tissue—Fat tissue.
Appetite suppressant—Drug that decreases feelings of hunger. Most work by increasing levels of
serotonin or catecholamine, chemicals in the brain
that control appetite.
Bariatrics—The branch of medicine that deals with
the prevention and treatment of obesity and related
disorders.
Ghrelin—A recently discovered peptide hormone
secreted by cells in the lining of the stomach.
Ghrelin is important in appetite regulation and
maintaining the body’s energy balance.
Hyperlipidemia—Abnormally high levels of lipids
in blood plasma.
Hyperplastic obesity—Excessive weight gain in
childhood, characterized by the creation of new
fat cells.
Hypertension—High blood pressure.
Hypertrophic obesity—Excessive weight gain in
adulthood, characterized by expansion of already
existing fat cells.
Ideal weight—Weight corresponding to the lowest
death rate for individuals of a specific height, gender,
and age.
Leptin—A protein hormone that affects feeding
behavior and hunger in humans. At present it is
thought that obesity in humans may result in part
from insensitivity to leptin.

obesity. Metformin (Glucophage), a drug that was
approved by the Food and Dug Administration
(FDA) in 1994 for the treatment of type 2 diabetes,
shows promise in treating obesity associated with
insulin resistance.
Another field of obesity research is the study of
hormones, particularly leptin, which is produced by
fat cells in the body, and ghrelin, which is secreted by
cells in the lining of the stomach. Both hormones are
known to affect appetite and the body’s energy
balance. Leptin is also related to reproductive function, while ghrelin stimulates the pituitary gland to
release growth hormone. Further studies of these
two hormones may lead to the development of new
medications to control appetite and food intake.
A third approach to obesity treatment involves
research into the social factors that encourage or
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Nutritional Disorders: Obesity.’’ Section 1, Chapter 5.
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Flancbaum, Louis, MD, with Erica Manfred and Deborah
Biskin. The Doctor’s Guide to Weight Loss Surgery.
West Hurley, NY: Fredonia Communications, 2001.
Pi-Sunyer, F. Xavier. ‘‘Obesity.’’ In Cecil Textbook of
Medicine, edited by Russel L. Cecil, et al. Philadelphia,
PA: W. B. Saunders Company, 2000.
PERIODICALS

Aronne, L. J., and K. R. Segal. ‘‘Weight Gain in the
Treatment of Mood Disorders.’’ Journal of Clinical
Psychiatry 64, Supplement 8 (2003): 22–29.
Bell, S. J., and G. K. Goodrick. ‘‘A Functional Food
Product for the Management of Weight.’’ Critical
Reviews in Food Science and Nutrition 42 (March 2002):
163–178.
Brudnak, M. A. ‘‘Weight-Loss Drugs and Supplements:
Are There Safer Alternatives?’’ Medical Hypotheses 58
(January 2002): 28–33.
Colquitt, J., A. Clegg, M. Sidhu, and P. Royle. ‘‘Surgery for
Morbid Obesity.’’ Cochrane Database Systems Review
2003: CD003641.
Espelund, U., T. K. Hansen, H. Orskov, and J. Frystyk.
‘‘Assessment of Ghrelin.’’ APMIS Supplementum 109
(2003): 140–145.
Hundal, R. S., and S. E. Inzucchi. ‘‘Metformin: New
Understandings, New Uses.’’ Drugs 63 (2003):
1879–1894.
Pirozzo, S., C. Summerbell, C. Cameron, and P. Glasziou.
‘‘Advice on Low-Fat Diets for Obesity (Cochrane
Review).’’ Cochrane Database Systems Review 2002:
CD003640.
Schurgin, S., and R. D. Siegel. ‘‘Pharmacotherapy of
Obesity: An Update.’’ Nutrition in Clinical Care 6
(January-April 2003): 27–37.
Shekelle, P. G., M. L. Hardy, S. C. Morton, et al. ‘‘Efficacy
and Safety of Ephedra and Ephedrine for Weight Loss
and Athletic Performance: A Meta-Analysis.’’ Journal
of the American Medical Association 289 (March 26,
2003): 1537–1545.
Tataranni, P. A. ‘‘Treatment of Obesity: Should We Target
the Individual or Society?’’ Current Pharmaceutical
Design 9 (2003): 1151–1163.
Veniant, M. M., and C. P. LeBel. ‘‘Leptin: From Animals to
Humans.’’ Current Pharmaceutical Design 9 (2003):
811–818.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Dietetic Association. (800) 877-1600.
<www.eatright.org.>.
American Obesity Association (AOA). 1250 24th Street
NW, Suite 300, Washington, DC 20037. (202) 776-7711
or (800) 98-OBESE. <www.obesity.org>.
American Society for Bariatric Surgery. 7328 West
University Avenue, Suite F, Gainesville, FL 32607.
(352) 331-4900. <www.asbs.org>.
American Society of Bariatric Physicians. 5453 East Evans
Place, Denver, CO 80222-5234. (303) 770-2526.
<www.asbp.org>.
HCF Nutrition Research Foundation, Inc. P.O. Box 22124,
Lexington, KY 40522. (606) 276-3119.
National Institute of Diabetes and Digestive and Kidney
Diseases. 31 Center Drive, USC2560, Building 31,
Room 9A-04, Bethesda, MD 20892-2560. (301) 496-3583.
<www.niddk.nih/gov>.
National Obesity Research Foundation. Temple University,
Weiss Hall 867, Philadelphia, PA 19122.
Weight-Control Information Network. 1 Win Way,
Bethesda, MD 20896-3665. (301) 951-1120.
<www.navigator.tufts.edu/special/win.html>.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

Obesity surgery
Definition
Obesity surgery is an operation that reduces or
bypasses the stomach or small intestine so that
severely overweight people can achieve significant
and permanent weight loss.

Purpose
Obesity surgery, also called bariatric surgery, is
performed only on severely overweight people who
are more than twice their ideal weight. This level of
obesity often is referred to as morbid obesity since
it can result in many serious, and potentially deadly,
health problems, including hypertension, Type II
diabetes mellitus (non-insulin dependent diabetes),
increased risk for coronary disease, increased unexplained heart attack, hyperlipidemia, and a higher
prevalence of colon, prostate, endometrial, and, possibly, breast cancer. In 2003, researchers concluded
that obesity surgery could cure Type II diabetes in
many people who were not yet morbidly obese.
Therefore, this surgery is performed on people whose
risk of complications of surgery is outweighed by the
2661

Obesity surgery

reinforce weight gain in humans. Researchers are
looking at such issues as the advertising and marketing
of food products; media stereotypes of obesity; the
development of eating disorders in adolescents and
adults; and similar questions.

Obesity surgery

need to lose weight to prevent health complications,
and for whom supervised weight loss and exercise
programs have repeatedly failed. Obesity surgery,
however, does not make people thin. Most people
lose about 60% of their excess weight through this
treatment. Changes in diet and exercise still are
required to maintain a normal weight.



Vertical banding gastroplasty. In this procedure, an
artificial pouch is created using staples in a different
section of the stomach. Plastic mesh is sutured into
part of the pouch to prevent it from dilating. In both
surgeries the food enters the small intestine farther
along that it would enter if exiting the stomach
normally. This reduces the time available for absorption of nutrients. The procedure is normally done
laparoscopically, meaning that the surgeon makes
one or more small incisions in the abdomen and
inserts the necessary tools and instruments through
the tiny holes. He or she can view the patient’s organs
via an inserted camera that displays pictures on a
monitor. This method makes for a faster and easier
recovery than a large incision.



Jejunoileal bypass. Now a rarely performed procedure, jejunoileal bypass involves shortening the small
intestine. Because of the high occurance of serious
complications involving chronic diarrhea and liver
disease, it has largely been abandoned for the other,
safer procedures

The theory behind obesity surgery is that if the
volume the stomach holds is reduced and the entrance
into the intestine is made smaller to slow stomach
emptying, or part of the small intestine is bypassed
or shortened, people will not be able to consume and/
or absorb as many calories. With obesity surgery the
volume of food the stomach can hold is reduced from
about four cups to about 1/2 cup.
Insurers may consider obesity surgery elective
surgery and not cover it under their policies.
Documentation of the necessity for surgery and
approval from the insurer should be sought before
this operation is performed.

Precautions
Obesity surgery should not be performed on
people who are less than twice their ideal weight. It
also is not appropriate for people who have substance
addictions or who have psychological disorders. Other
considerations in choosing candidates for obesity
surgery include the general health of the person and
his or her willingness to comply with follow-up
treatment.

Preparation
After patients are carefully selected as appropriate
for obesity surgery, they receive standard preoperative
blood and urine tests and meet with an anesthesiologist
to discuss how their health may affect the administration
of anesthesia. Pre-surgery counseling is done to help
patients anticipate what to expect after the operation.

Aftercare
Description
Obesity surgery is usually performed in a hospital
by a surgeon who has experience with obesity surgery
or at a center that specializes in the procedure. General
anesthesia is used, and the operation takes 2–3 hours.
The hospital stay lasts about a week.
Three procedures are currently used for obesity
surgery:


Gastric bypass surgery. Probably the most common
type of obesity surgery, gastric bypass surgery has
been performed in the United States for about 25
years. In this procedure, the volume of the stomach
is reduced by four rows of stainless steel staples that
separate the main body of the stomach from a small,
newly created pouch. The pouch is attached at one
end to the esophagus. At the other end is a very small
opening into the small intestine. Food flows through
this pouch, bypassing the main portion of the stomach
and emptying slowly into the small intestine where it is
absorbed.

2662

Immediately after the operation, most patients
are restricted to a liquid diet for 2–3 weeks; however,
some may remain on it for up to 12 weeks. Patients
then move on to a diet of pureed food for about a
month, and, after about two months, most can tolerate solid food. High fat food is restricted because it
is hard to digest and causes diarrhea. Patients are
expected to work on changing their eating and exercise
habits to assist in weight loss. Most people eat 3–4 small
meals a day once they return to solid food. Eating too
quickly or too much after obesity surgery can cause
nausea and vomiting as well as intestinal ‘‘dumping,’’
a condition in which undigested food is shunted too
quickly into the small intestine, causing pain, diarrhea,
weakness, and dizziness.

Risks
As in any abdominal surgery, there is always a risk
of excessive bleeding, infection, and allergic reaction
to anesthesia. Specific risks associated with obesity
GALE ENCYCLOPEDIA OF MEDICINE

Obesity surgery

Gastric bypass

Vertical banded gastroplasty

The purpose of obesity surgery is to reduce the size of the stomach and slow the stomach emptying process by narrowing the
entrance into the intestine. With this surgery, the volume of food the stomach can hold is reduced from approximately 4 cups to
approximately one-half cup. There are two types of procedures used for obesity surgery: gastric bypass surgery and vertical
banded gastroplasty, as shown in the illustration above. (Illustration by Electronic Illustrators Group.)

surgery include leaking or stretching of the pouch and
loosening of the gastric staples. Although the average
death rate associated with this procedure is less than
one percent, the rate varies from center to center, ranging from 0–4%. Long-term failure rates can reach
50%, sometimes making additional surgery necessary.
Other complications of obesity surgery include an intolerance to foods high in fats, lactose intolerance, bouts of
vomiting, diarrhea, and intestinal discomfort
Studies on the risks of these surgeries continue.
A 2003 report showed that gastric bypass surgery risk
increases with age, weight and male gender. Patients
age 55 and older experienced more complications
than did younger patients and male patients had more
life-threatening complications than female patients,
particularly those who were more severely obese.

Normal results
Many people lose about 60% of the weight they
need to reach their ideal weight through obesity surgery. However, surgery is not a magic weight-loss
GALE ENCYCLOPEDIA OF MEDICINE

operation, and success also depends on the patient’s
willingness to exercise and eat low-calorie foods.
A 2003 report showed that super obese patients had
a lower success rate with laparoscopic vertical banding
gastroplasty than those considered morbidly obese.
However, the overall success rate was nearly 77% of
patients carrying less than 50% excess weight four
years after the procedure.
Resources
PERIODICALS

‘‘Gastric Bypass Surgery Risk Increases with Age, Weight,
and Male Gender.’’ Medical Devices and Surgical
Technology Week January 19, 2003: 29.
‘‘Laparoscopic Vertical Banding Gastroplasty Safe and
Effective for Morbid Obesity.’’ Medical Devices and
Surgical Technology Week January 19, 2003: 2.
Sadovsky, Richard. ‘‘Obesity Surgery May Cure Diabetes in
Nonobese Patients.’’ American Family Physician 56
(February 15, 2003): 866.

Tish Davidson, A.M.
Teresa G. Odle
2663

Obsessive-compulsive disorder

Obsessive-compulsive
disorder
Definition
Obsessive-compulsive disorder (OCD) is a type
of anxiety disorder. Anxiety disorder is the experience
of prolonged, excessive worry about circumstances
in one’s life. OCD is characterized by distressing repetitive thoughts, impulses or images that are intense,
frightening, absurd, or unusual. These thoughts are
followed by ritualized actions that are usually bizarre
and irrational. These ritual actions, known as compulsions, help reduce anxiety caused by the individual’s
obsessive thoughts. Often described as the ‘‘disease of
doubt,’’ the sufferer usually knows the obsessive
thoughts and compulsions are irrational but, on
another level, fears they may be true.

Description
Almost one out of every 40 people will suffer from
obsessive-compulsive disorder at some time in their
lives. The condition is two to three times more common
than either schizophrenia or manic depression, and
strikes men and women of every ethnic group, age
and social level. Because the symptoms are so distressing, sufferers often hide their fears and rituals but
cannot avoid acting on them. OCD sufferers are often
unable to decide if their fears are realistic and need to be
acted upon.
Most people with obsessive-compulsive disorder
have both obsessions and compulsions, but occasionally a person will have just one or the other. The degree
to which this condition can interfere with daily living
also varies. Some people are barely bothered, while
others find the obsessions and compulsions to be profoundly traumatic and spend much time each day in
compulsive actions.
Obsessions are intrusive, irrational thoughts that
keep popping up in a person’s mind, such as ‘‘my
hands are dirty, I must wash them again.’’ Typical
obsessions include fears of dirt, germs, contamination,
and violent or aggressive impulses. Other obsessions
include feeling responsible for others’ safety, or an
irrational fear of hitting a pedestrian with a car.
Additional obsessions can involve excessive religious
feelings or intrusive sexual thoughts. The patient may
need to confess frequently to a religious counselor or
may fear acting out the strong sexual thoughts in a
hostile way. People with obsessive-compulsive disorder may have an intense preoccupation with order
and symmetry, or be unable to throw anything out.
2664

Compulsions usually involve repetitive rituals
such as excessive washing (especially handwashing or
bathing), cleaning, checking and touching, counting,
arranging or hoarding. As the person performs these
acts, he may feel temporarily better, but there is no
long-lasting sense of satisfaction or completion after
the act is performed. Often, a person with obsessivecompulsive disorder believes that if the ritual is not
performed, something dreadful will happen. While
these compulsions may temporarily ease stress, shortterm comfort is purchased at a heavy price—time spent
repeating compulsive actions and a long-term interference with life.
The difference between OCD and other compulsive behavior is that while people who have problems
with gambling, overeating or with substance abuse
may appear to be compulsive, these activities also
provide pleasure to some degree. The compulsions of
OCD, on the other hand, are never pleasurable.
OCD may be related to some other conditions,
such as the continual urge to pull out body hair
(trichotillomania) fear of having a serious disease
(hypochondriasis) or preoccupation with imagined
defects in personal appearance disorder (body dysmorphia). Some people with OCD also have Tourette
syndrome, a condition featuring tics and unwanted
vocalizations (such as swearing). OCD is often linked
with depression and other anxiety disorders.

Causes and symptoms
While no one knows for sure, research suggests
that the tendency to develop obsessive-compulsive
disorder is inherited. There are several theories behind
the cause of OCD. Some experts believe that OCD is
related to a chemical imbalance within the brain that
causes a communication problem between the front
part of the brain (frontal lobe) and deeper parts of the
brain responsible for the repetitive behavior. Research
has shown that the orbital cortex located on the underside of the brain’s frontal lobe is overactive in OCD
patients. This may be one reason for the feeling of
alarm that pushes the patient into compulsive, repetitive actions. It is possible that people with OCD
experience overactivity deep within the brain that
causes the cells to get ‘‘stuck,’’ much like a jammed
transmission in a car damages the gears. This could
lead to the development of rigid thinking and repetitive movements common to the disorder. The fact that
drugs which boost the levels of serotonin, a brain
messenger substance linked to emotion and many
different anxiety disorders, in the brain can reduce
OCD symptoms may indicate that to some degree
OCD is related to levels of serotonin in the brain.
GALE ENCYCLOPEDIA OF MEDICINE

If one person in a family has obsessive-compulsive
disorder, there is a 25% chance that another immediate family member has the condition. It also appears
that stress and psychological factors may worsen
symptoms, which usually begin during adolescence
or early adulthood.

Cognitive-behavioral therapy (CBT) teaches
patients how to confront their fears and obsessive
thoughts by making the effort to endure or wait out
the activities that usually cause anxiety without compulsively performing the calming rituals. Eventually
their anxiety decreases. People who are able to alter
their thought patterns in this way can lessen their
preoccupation with the compulsive rituals. At the
same time, the patient is encouraged to refocus attention elsewhere, such as on a hobby.
In a few severe cases where patients have not
responded to medication or behavioral therapy,
brain surgery may be tried as a way of relieving the
unwanted symptoms. Surgery can help up to a third of
patients with the most severe form of OCD. The most
common operation involves removing a section of the
brain called the cingulate cortex. The serious side
effects of this surgery for some patients include
seizures, personality changes and less ability to plan.

Alternative treatment
Diagnosis
People with obsessive-compulsive disorder feel
ashamed of their problem and often try to hide their
symptoms. They avoid seeking treatment. Because
they can be very good at keeping their problem from
friends and family, many sufferers do not get the help
they need until the behaviors are deeply ingrained
habits and hard to change. As a result, the condition
is often misdiagnosed or underdiagnosed. All too often,
it can take more than a decade between the onset of
symptoms and proper diagnosis and treatment.
While scientists seem to agree that OCD is related
to a disruption in serotonin levels, there is no blood
test for the condition. Instead, doctors diagnose OCD
after evaluating a person’s symptoms and history.

Because OCD sometimes responds to SSRI antidepressants, a botanical medicine called St. John’s wort
(Hypericum perforatum) might have some beneficial
effect as well, according to herbalists. Known popularly
as ‘‘Nature’s Prozac,’’ St. John’s wort is prescribed by
herbalists for the treatment of anxiety and depression.
They believe that this herb affects brain levels of serotonin in the same way that SSRI antidepressants do.
Herbalists recommend a dose of 300 mg., three times
per day. In about one out of 400 people, St. John’s wort
(like Prozac) may initially increase the level of anxiety.
Homeopathic constitutional therapy can help rebalance
the patient’s mental, emotional, and physical well-being,
allowing the behaviors of OCD to abate over time.

Prognosis
Treatment
Obsessive-compulsive disorder can be effectively
treated by a combination of cognitive-behavioral therapy and medication that regulates the brain’s serotonin
levels. Drugs that are approved to treat obsessivecompulsive disorder include fluoxetine (Prozac),
fluvoxamine (Luvox), paroxetine (Paxil), and sertraline
(Zoloft), all selective serotonin reuptake inhibitors
(SSRIs) that affect the level of serotonin in the brain.
Older drugs include the antidepressant clomipramine
(Anafranil), a widely-studied drug in the treatment of
OCD, but one that carries a greater risk of side effects.
Drugs should be taken for at least 12 weeks before
deciding whether or not they are effective.
GALE ENCYCLOPEDIA OF MEDICINE

Obsessive-compulsive disorder is a chronic disease
that, if untreated, can last for decades, fluctuating from
mild to severe and worsening with age. When treated by
a combination of drugs and behavioral therapy, some
patients go into complete remission. Unfortunately, not
all patients have such a good response. About 20% of
people cannot find relief with either drugs or behavioral
therapy. Hospitalization may be required in some cases.
Despite the crippling nature of the symptoms,
many successful doctors, lawyers, business people,
performers and entertainers function well in society
despite their condition. Nevertheless, the emotional
and financial cost of obsessive-compulsive disorder
can be quite high.
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Obsessive-compulsive disorder

Recently, scientists have identified an intriguing
link between childhood episodes of strep throat and
the development of OCD. It appears that in some
vulnerable children, strep antibodies attack a certain
part of the brain. Antibodies are cells that the body
produces to fight specific diseases. That attack results
in the development of excessive washing or germ
phobias. A phobia is a strong but irrational fear. In
this instance the phobia is fear of disease germs present
on commonly handled objects. These symptoms would
normally disappear over time, but some children who
have repeated infections may develop full-blown OCD.
Treatment with antibiotics has resulted in lessening of
the OCD symptoms in some of these children.

Obstetrical emergencies

KEY TERMS
Anxiety disorder—This is the experience of prolonged, excessive worry about circumstances in
one’s life. It disrupts daily life.
Cognitive-behavior therapy—A form of psychotherapy that seeks to modify behavior by manipulating the environment to change the patient’s
response.
Compulsion—A rigid behavior that is repeated over
and over each day.
Obsession—A recurring, distressing idea, thought
or impulse that feels ‘‘foreign’’ or alien to the
individual.
Selective serotonin reuptake inhibitors (SSRIs)—
A class of antidepressants that work by blocking the
reabsorption of serotonin in brain cells, raising the
level of the chemical in the brain. SSRIs include
Prozac, Zoloft, Luvex, and Paxil.
Serotonin—One of three major neurotransmitters
found in the brain that is related to emotion, and
is linked to the development of depression and
obsessive-compulsive disorder.

Resources
ORGANIZATIONS

Anxiety Disorders Association of America. 11900 Park
Lawn Drive, Ste. 100, Rockville, MD 20852.
(800) 545-7367. <http://www.adaa.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington,
VA 22201-3042. (800) 950-6264. <http://
www.nami.org>.
National Anxiety Foundation. 3135 Custer Dr., Lexington,
KY 40517. (606) 272-7166. <http://www.lexingtonon-line.com/naf.html>.
Obsessive-Compulsive Anonymous. P.O. Box 215,
New Hyde Park, NY 11040. (516) 741-4901.
<west24th@aol.com> <http://members.aol.com/
west24th/index.html>.
Obsessive-Compulsive Foundation. P.O. Box 70, Milford, CT
06460. (203) 874-3843. <JPHS28A@Prodigy.com>
<http://pages.prodigy.com/alwillen/ocf.html>.

Carol A. Turkington

Obsessive compulsive personality disorder
see Personality disorders
Obstetric sonogram see Pelvic ultrasound
2666

Obstetrical emergencies
Definition
Obstetrical emergencies are life-threatening
medical conditions that occur in pregnancy or during
or after labor and delivery.

Description
There are a number of illnesses and disorders
of pregnancy that can threaten the well-being of
both mother and child. Obstetrical emergencies may
also occur during active labor, and after delivery
(postpartum).
Obstetrical emergencies of pregnancy
ECTOPIC PREGNANCY. An ectopic, or tubal, pregnancy occurs when the fertilized egg implants itself
in the fallopian tube rather than the uterine wall.
If the pregnancy is not terminated at an early stage,
the fallopian tube will rupture, causing internal
hemorrhaging and potentially resulting in permanent
infertility.
PLACENTAL ABRUPTION. Also called abruptio
placenta, placental abruption occurs when the
placenta separates from the uterus prematurely,
causing bleeding and contractions. If over 50% of
the placenta separates, both the fetus and mother
are at risk.
PLACENTA PREVIA. When the placenta attaches to
the mouth of the uterus and partially or completely
blocks the cervix, the position is termed placenta previa
(or low-lying placenta). Placenta previa can result
in premature bleeding and possible postpartum
hemorrhage.
PREECLAMPSIA/ECLAMPSIA. Preeclampsia (toxemia),
or pregnancy-induced high blood pressure, causes
severe edema (swelling due to water retention) and
can impair kidney and liver function. The condition
occurs in approximately 5% of all United States
pregnancies. If it progresses to eclampsia, toxemia is
potentially fatal for mother and child.
PREMATURE
RUPTURE
OF
MEMBRANES
(PROM). Premature rupture of membranes is the

breaking of the bag of waters (amniotic fluid)
before contractions or labor begins. The situation
is only considered an emergency if the break occurs
before thirty-seven weeks and results in significant
leakage of amniotic fluid and/or infection of the
amniotic sac.
GALE ENCYCLOPEDIA OF MEDICINE

AMNIOTIC FLUID EMBOLISM. A rare but frequently
fatal complication of labor, this condition occurs
when amniotic fluid embolizes from the amniotic sac
and through the veins of the uterus and into the circulatory system of the mother. The fetal cells present in
the fluid then block or clog the pulmonary artery,
resulting in heart attack. This complication can also
happen during pregnancy, but usually occurs in the
presence of strong contractions.
INVERSION OR RUPTURE OF UTERUS. During labor,
a weak spot in the uterus (such as a scar or a uterine
wall that is thinned by a multiple pregnancy) may
tear, resulting in a uterine rupture. In certain circumstances, a portion of the placenta may stay attached to
the wall and will pull the uterus out with it during
delivery. This is called uterine inversion.
PLACENTA ACCRETA. Placenta accreta occurs when
the placenta is implanted too deeply into the uterine
wall, and will not detach during the late stages of
childbirth, resulting in uncontrolled bleeding.
PROLAPSED UMBILICAL CORD. A prolapse of the
umbilical cord occurs when the cord is pushed down
into the cervix or vagina. If the cord becomes compressed, the oxygen supply to the fetus could be diminished, resulting in brain damage or possible death.
SHOULDER DYSTOCIA. Shoulder dystocia occurs

when the baby’s shoulder(s) becomes wedged in the
birth canal after the head has been delivered.



Leaking amniotic fluid. Amniotic fluid is strawcolored and may easily be confused with urine leakage,
but can be differentiated by its slightly sweet odor.



Severe abdominal pain. Stomach or lower back pain
can indicate preeclampsia or an undiagnosed ectopic
pregnancy. Postpartum stomach pain can be a sign
of infection or hemorrhage.



Contractions. Regular contractions before 37 weeks
of gestation can signal the onset of preterm labor due
to obstetrical complications.



Abrupt and rapid increase in blood pressure.
Hypertension is one of the first signs of toxemia.



Edema. Sudden and significant swelling of hands and
feet caused by fluid retention from toxemia.



Unpleasant smelling vaginal discharge. A thick,
malodorous discharge from the vagina can indicate
a postpartum infection.



Fever. Fever may indicate an active infection.



Loss of consciousness. Shock due to blood loss
(hemorrhage) or amniotic embolism can precipitate
a loss of consciousness in the mother.



Blurred vision and headaches. Vision problems and
headache are possible symptoms of preeclampsia.

Diagnosis
Obstetrical emergencies postpartum
POSTPARTUM HEMORRHAGE OR INFECTION. Severe
bleeding or uterine infection occurring after delivery is
a serious, potentially fatal situation.

Causes and symptoms
Obstetrical emergencies can be caused by a number of factors, including stress, trauma, genetics, and
other variables. In some cases, past medical history,
including previous pregnancies and deliveries, may
help an obstetrician anticipate the possibility of
complications.
Signs and symptoms of an obstetrical emergency
include, but are not limited to:


Diminished fetal activity. In the late third trimester,
fewer than ten movements in a two hour period may
indicate that the fetus is in distress.



Abnormal bleeding. During pregnancy, brown or
white to pink vaginal discharge is normal, bright

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis of an obstetrical emergency typically
takes place in a hospital or other urgent care facility.
A specialist will take the patient’s medical history and
perform a pelvic and general physical examination.
The mother’s vital signs are taken, and if preeclampsia
is suspected, blood pressure may be monitored over
a period of time. The fetal heartbeat is assessed with
a doppler stethoscope, and diagnostic blood and
urine tests of the mother may also be performed,
including laboratory analysis for protein and/or
bacterial infection. An abdominal ultrasound may
aid in the diagnosis of any condition that involves
a malpositioned placenta, such as placenta previa or
placenta abruption.
In cases where an obstetrical complication is suspected, a fetal heart monitor is positioned externally
on the mother’s abdomen. If the fetal heart rate is
erratic or weak, or if it does not respond to movement, the fetus may be in distress. A biophysical
profile (BPP) may also be performed to evaluate the
health of the fetus. The BPP uses data from an
2667

Obstetrical emergencies

red blood or blood containing large clots is not.
After delivery, continual blood loss of over 500 ml
indicates hemorrhage.

Obstetrical emergencies during labor and delivery

Obstetrical emergencies

ultrasound examination to analyze the fetus size,
movement, heart rate, and surrounding amniotic
fluid.
If the mother’s membranes have ruptured and her
cervix is partially dilated, an internal fetal scalp electrode can be inserted through the vagina to assess
heart rate. A fetal oximetry monitor that measures
the oxygen saturation levels of the fetus may also be
attached to the scalp.

Treatment
Obstetrical emergencies of pregnancy
ECTOPIC PREGNANCY. Treatment of an ectopic
pregnancy is laparoscopic surgical removal of the fertilized ovum. If the fallopian tube has burst or been
damaged, further surgery will be necessary.
PLACENTAL ABRUPTION. In mild cases of placental
abruption, bed rest may prevent further separation of
the placenta and stem bleeding. If a significant abruption (over 50%) occurs, the fetus may have to be
delivered immediately and a blood transfusion may
be required.
PLACENTA PREVIA. Hospitalization or highly restricted at-home bed rest is usually recommended if
placenta previa is diagnosed after the twentieth week
of pregnancy. If the fetus is at least 36 weeks old and
the lungs are mature, a cesarean section is performed
to deliver the baby.
PREECLAMPSIA/ECLAMPSIA. Treatment of preeclampsia depends upon the age of the fetus and
the acuteness of the condition. A woman near full
term who has only mild toxemia may have labor
induced to deliver the child as soon as possible.
Severe preeclampsia in a woman near term also
calls for immediate delivery of the child, as this is
the only known cure for the condition. However, if
the fetus is under 28 weeks, the mother may be
hospitalized and steroids may be administered to
try to hasten lung development in the fetus. If the
life of the mother or fetus appears to be in danger,
the baby is delivered immediately, usually by cesarean section.
PREMATURE RUPTURE OF MEMBRANES (PROM). If
PROM occurs before 37 weeks and/or results in
significant leakage of amniotic fluid, a course of intravenous antibiotics is started. A culture of the cervix
may be taken to analyze for the presence of bacterial
infection. If the fetus is close to term, labor is typically
induced if contractions do not start within 24 hours of
rupture.

2668

Obstetrical emergencies during labor and delivery
AMNIOTIC FLUID EMBOLISM. The stress of contrac-

tions can cause this complication, which has a high
mortality rate. Administering steroids to the mother
and delivering the fetus as soon as possible is the
standard treatment.
INVERSION OR RUPTURE OF UTERUS. An inverted
uterus is either manually or surgical replaced to the
proper position. A ruptured uterus is repaired if
possible, although if the damage is extreme, a hysterectomy (removal of the uterus) may be performed.
A blood transfusion may be required in either case if
hemorrhaging occurs.
PLACENTA ACCRETA. Women who experience placenta accreta will typically need to have their placenta
surgically removed after delivery. Hysterectomy is
necessary in some cases.
PROLAPSED UMBILICAL CORD. Saline may be
infused into the vagina to relieve the compression. If
the cord has prolapsed out the vaginal opening, it
may be replaced, but immediate delivery by cesarean
section is usually indicated.

Obstetrical emergencies postpartum
POSTPARTUM HEMORRHAGE OR INFECTION. The
source of the hemorrhage is determined, and blood
transfusion and IV fluids are given as necessary.
Oxytocic drugs may be administered to encourage
contraction of the uterus. Retained placenta is a
frequent cause of persistent bleeding, and surgical
removal of the remaining fragments (curettage) may
be required. Surgical repair of lacerations to the birth
canal or uterus may be required. Drugs that encourage
coagulation (clotting) of the blood may be administered to stem the bleeding. Infrequently, hysterectomy
is required.

In cases of infection, a course of intravenous
antibiotics is prescribed. Most postpartum infections
occur in the endometrium, or lining of the uterus,
and may be also caused by a piece of retained
placenta. If this is the case, it will also require surgical
removal.
SHOULDER DYSTOCIA. The mother is usually positioned with her knees to her chest, known as the
McRoberts maneuver, in an effort to free the child’s
shoulder. An episiotomy is also performed to widen the
vaginal opening. If the shoulder cannot be dislodged
from the pelvis, the baby’s clavicle (collarbone) may
have to be broken to complete the delivery before a
lack of oxygen causes brain damage to the infant.

GALE ENCYCLOPEDIA OF MEDICINE

Amniotic fluid—The liquid in the placental sac
that cushions the fetus and regulates temperature
in the placental environment. Amniotic fluid also
contains fetal cells.
Cesarean section—The surgical delivery of a fetus
through an incision in the uterus.

National Institute of Child Health and Human
Development (NICHD) Clearinghouse. Bldg 31, Room
2A32, MSC 2425, 31 Center Drive, Bethesda, MD
20892-2425. (800) 370-2943. <http://www.nichd.nih.
gov/publications/health.htm>.

Paula Anne Ford-Martin

Embolism—Blood vessel obstruction by a blood
clot or other substance (i.e., air, cell matter).
Episiotomy—Incision of the perineum, the area
between the vulva and the anus, to assist delivery
and avoid severe tearing of the perineum.
Laparoscopic—A minimally-invasive surgical or
diagnostic procedure that uses a flexible endoscope
(laparoscope) to view and operate on structures in
the abdomen.
Postpartum—After childbirth.

Occupational asthma
Definition
Occupational asthma is a form of lung disease in
which the breathing passages shrink, swell, or become
inflamed or congested as a result of exposure to irritants in the workplace.

Description
Prognosis
If a fetus is close to full-term (37 weeks) and the
complication is detected early enough, the prognosis is
usually good for mother and child. With advances in
neonatal care, approximately 85% of infants weighing
less than 3 lbs 5 oz survive, and these infants are being
delivered at 28 weeks and younger. However, preterm
infants have a greater chance of serious medical
problems, and developmental disabilities occur in
25–50%. They also have a higher incidence of learning
disorders, and are four to six times more likely to
be diagnosed with attention-deficit hyperactivity
disorder (ADHD).

Prevention
Proper prenatal care is the best prevention for
obstetrical emergencies. When complications of pregnancy do arise, pregnant women who see their OB/
GYN on a regular basis are more likely to get an early
diagnosis, and with it, the best chance for fast and
effective treatment. In addition, eating right and
taking prenatal vitamins and supplements as recommended by a physician will also contribute to the
health of both mother and child.
Resources
PERIODICALS

Chamberlain, Geoffrey, and Phillip Steer. ‘‘Obstetric
Emergencies.’’ British Medical Journal. 318, no.7194
(May 1999): 1342.
GALE ENCYCLOPEDIA OF MEDICINE

As many as 15% of all cases of asthma may be
related to on-the-job exposure to:


animal hair



dander



dust composed of bacteria, protein, or organic
matter like cereal, grains, cotton, and flax



fumes created by metal soldering



insulation and packaging materials



mites and other insects



paints

Hundreds of different types of jobs involve exposure to substances that could trigger occupational
asthma, but only a small fraction of people who do
such work develop this disorder. Occupational asthma
is most apt to affect workers who have personal or
family histories of allergies or asthma, or who are
often required to handle or breathe dust or fumes
created by especially irritating material.

Causes and symptoms
Although occupational asthma is not new, today,
more than 240 causes of occupational asthma have
been identified. It was probably first recorded in
1713 when one of the fathers of occupational health,
Bernadina Ramazzini said bakers and textile workers
had problems with coughing shortness of breath, hoarseness and asthma. Even short-term exposure to low
levels of one or more irritating substances can cause
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Occupational asthma

ORGANIZATIONS

KEY TERMS

Occupational asthma

A L I C E H A M I L T O N (1869–1970)
an undergraduate degree and taking surprisingly few science
courses. Realizing that she wanted to pursue research rather
than medical practice, Hamilton went on to do further
studies both in the United States and abroad: from 1895–
1896 at Leipzig and Munich; 1896–1897 at Johns Hopkins;
and 1902 in Paris at the Pasteur Institute. In 1897 she
accepted a post as professor of pathology at the Women’s
Medical College at Northwestern University in Chicago.
In Chicago Hamilton became a resident of Hull
House, the pioneering settlement designed to give care
and advice to the poor of Chicago. Here, under the influence of Jane Addams, the founder of Hull House, Hamilton
saw the effects of poverty up close, leading her to a lifelong
career focused on industrial medicine.

(AP/Wide World Photos. Reproduced by permission.)

Alice Hamilton was born on February 27, 1869, in
New York City, the second of five children born to
Montgomery Hamilton, a wholesale grocer, and Gertrude
(Pond) Hamilton. She earned a medical degree from the
University of Michigan in 1893, without having completed

Occupations Associated With Asthma

Animal Handling
Bakeries
Health Care
Jewelry Making
Laboratory Work
Manufacturing Detergents
Nickel Plating
Soldering
Snow Crab and Egg Processing
Tanneries

Alice Hamilton was a pioneer in correcting the medical problems caused by industrialization, awakening the
country in the early twentieth century to the dangers of
industrial poisons and hazardous working conditions.
Through her untiring efforts, toxic substances in the lead,
mining, painting, pottery, and rayon industries were
exposed and legislation passed to protect workers. She
was also a champion of worker’s compensation laws, and
was instrumental in bringing about this type of legislation
in the state of Illinois. A medical doctor and researcher, she
was the first woman of faculty status at Harvard University,
and was a consultant on governmental commissions, both
domestic and foreign.

wheezing. Symptoms may appear less than 24 hours
after the person is first exposed to the irritant or
develop two or three years later.
At first, symptoms appear while the person is at
work or several hours after the end of the workday.
Symptoms disappear or diminish when the person
spends time away from the workplace and return or
intensify when exposure is renewed.
As the condition becomes more advanced, symptoms sometimes occur even when the person is not in
the workplace. Symptoms may also develop in
response to minor sources of lung irritation.

Diagnosis
a very sensitive person to develop symptoms of occupational asthma. A person who has occupational
asthma has one or more symptoms, including coughing, shortness of breath, tightness in the chest, and
2670

An allergist, occupational medicine specialist, or a
doctor who treats lung disease performs a thorough
physical examination and takes a medical history that
explores:
GALE ENCYCLOPEDIA OF MEDICINE

the kind of work the patient has done



the types of exposures the patient may have
experienced



what symptoms the patient has had



when, how often, and how severely symptoms have
occurred

Performed before and after work, pulmonary
function tests can show how job-related exposures
affect the airway. Laboratory analysis of blood and
sputum may confirm a diagnosis of workplace
asthma. To pinpoint the cause more precisely, the
doctor may ask the patient to inhale specific substances and monitor the body’s response to them.
This is called a challenge test.

Treatment
The most effective treatment for occupational
asthma is to reduce or eliminate exposure to symptomproducing substances.
Medication may be prescribed for workers who
can not prevent occasional exposure. Leukotriene
modifiers (montelukast and zafirlukast) are new
drugs that help manage asthma. They work by counteracting leukotrienes, which are substances released
by white blood cells in the lung that cause the air
passages to constrict and promote mucus secretion.
Leukotriene modifiers also fight off some forms of
rhinitis, an added bonus for people with asthma.
Medication, physical therapy, and breathing aids
may be needed to relieve symptoms of advanced occupational asthma involving airway damage.
A patient who has occupational asthma should
learn what causes symptoms and how to control
them, and what to do when an asthma attack occurs.
Because asthma symptoms and the substances
that provoke them can change, a patient who has
occupational asthma should be closely monitored by
a family physician, allergist, or doctor who specializes
in occupational medicine or lung disease.

In time, occupational asthma can cause asthmalike symptoms to occur when the patient is exposed to
tobacco smoke, household dust, and other ordinary
irritants.
Smoking aggravates symptoms of occupational
asthma. Patients who eliminate workplace exposure
and stop smoking are more apt to recover fully than
those who change jobs but continue to smoke.

Prevention
Industries and environments where employees
have a heightened exposure to substances known
to cause occupational asthma can take measures to
diminish or eliminate the amount of pollution in
the atmosphere or decrease the number of exposed
workers.
Regular medical screening of workers in these
environments may enable doctors to diagnose occupational asthma before permanent lung damage takes
place.
Resources
PERIODICALS

‘‘Allergic to Work? Occupational Asthma Accounts for Up
to 18 Million Lost Working Days a Year and Affects
Thousand of Workers.’’ The Safety & Health
Practitioner September 2004: 38–41.
Solomon, Gina, Elizabeth H. Humphreys, and Mark
D. Miller. ‘‘Asthma and the Environment: Connecting
the Dots: What Role Do Environmental Exposures
Play in the Rising Prevalence and Severity of
Asthma?’’ Contemporary Peditatrics August 2004:
73–81.
‘‘What’s New in: Asthma and Allergic Rhinitis.’’ Pulse
September 20, 2004: 50.
ORGANIZATIONS

American College of Allergy, Asthma and Immunology. 85
West Algonquin Road, Suite 550, Arlington Heights,
IL 60005. (847) 427-1200.

Maureen Haggerty
Teresa G. Odle

Prognosis
Occupational can be reversible. However, continued exposure to the symptom-producing substance
can cause permanent lung damage. Follow-up studies
of people with occupational asthma show that some
cannot be protected from the exposure or are forced
to change jobs, lose their jobs, or have worse prospects for future jobs based on their allergies and
asthma.
GALE ENCYCLOPEDIA OF MEDICINE

Occupational therapy see Rehabilitation
Ocular myopathy see Ophthalmoplegia
Ocular rosacea see Rosacea
Ofloxacin see Fluoroquinolones
Ohio Valley disease see Histoplasmosis
2671

Occupational asthma



Oligomenorrhea

Oligomenorrhea
Definition
Medical dictionaries define oligomenorrhea as
infrequent or very light menstruation. But physicians
typically apply a narrower definition, restricting the
diagnosis of oligomenorrhea to women whose periods
were regularly established before they developed
problems with infrequent flow. With oligomenorrhea,
menstrual periods occur at intervals of greater than
35 days, with only four to nine periods in a year.

Description
True oligomenorrhea can not occur until menstrual periods have been established. In the United
States, 97.5% of women have begun normal menstrual
cycles by age 16. The complete absence of menstruation, whether menstrual periods never start or whether
they stop after having been established, is called
amenorrhea. Oligomenorrhea can become amenorrhea
if menstruation stops for six months or more.

Professional ballet dancers, gymnasts, and ice
skaters are especially at risk for oligomenorrhea
because they combine strenuous physical activity
with a diet intended to keep their weight down.
Menstrual irregularities are now known to be one of
the three disorders comprising the so-called ‘‘female
athlete triad,’’ the other disorders being disordered
eating and osteoporosis. The triad was first formally
named at the annual meeting of the American College
of Sports Medicine in 1993, but doctors were aware of
the combination of bone mineral loss, stress fractures,
eating disorders, and participation in women’s sports
for several decades before the triad was named.
Women’s coaches have become increasingly aware of
the problem since the early 1990s, and are encouraging
female athletes to seek medical advice.

Causes and symptoms
Symptoms of oligomenorrhea include:


menstrual periods at intervals of more than 35 days



irregular menstrual periods with unpredictable flow

It is quite common for women at the beginning
and end of their reproductive lives to miss or have
irregular periods. This is normal and is usually the
result of imperfect coordination between the
hypothalamus, the pituitary gland, and the ovaries.
For no apparent reason, a few women menstruate
(with ovulation occurring) on a regular schedule as
infrequently as once every two months. For them that
schedule is normal and not a cause for concern.



some women with oligomenorrhea may have difficulty conceiving.

Women with polycystic ovary syndrome (PCOS) are
also likely to suffer from oligomenorrhea. PCOS is a
condition in which the ovaries become filled with small
cysts. Women with PCOS show menstrual irregularities
that range from oligomenorrhea and amenorrhea on the
one hand to very heavy, irregular periods on the other.
The condition affects about 6% of premenopausal
women and is related to excess androgen production.

The pituitary gland is then stimulated to produce
hormones that affect growth and reproduction. At the
beginning and end of a woman’s reproductive life,
some of these hormone messages may not be synchronized, causing menstrual irregularities.

Other physical and emotional factors also cause a
woman to miss periods. These include:


emotional stress



chronic illness



poor nutrition



eating disorders such as anorexia nervosa



excessive exercise



estrogen-secreting tumors



illicit use of anabolic steriod drugs to enhance
athletic performance

2672

Oligomenorrhea that occurs in adolescents is often
caused by immaturity or lack of synchronization
between the hypothalamus, pituitary gland, and ovaries.
The hypothalamus is part of the brain that controls
body temperature, cellular metabolism, and basic
functions such as eating, sleeping, and reproduction.
It secretes hormones that regulate the pituitary gland.

In PCOS, oligomenorrhea is probably caused
by inappropriate levels of both female and male hormones. Male hormones are produced in small quantities by all women, but in women with PCOS, levels of
male hormone (androgens) are slightly higher than in
other women. More recently, however, some researchers are hypothesizing that the ovaries of women with
PCOS are abnormal in other respects. In 2003, a group
of researchers in London reported that there are
fundamental differences between the development of
egg follicles in normal ovaries and follicle development in the ovaries of women with PCOS.
In athletes, models, actresses, dancers, and
women with anorexia nervosa, oligomenorrhea occurs
because the ratio of body fat to weight drops too low.
GALE ENCYCLOPEDIA OF MEDICINE

History and physical examination
Diagnosis of oligomenorrhea begins with the
patient informing the doctor about infrequent periods.
The doctor will ask for a detailed description of the
problem and take a history of how long it has existed
and any patterns the patient has observed. A woman
can assist the doctor in diagnosing the cause of oligomenorrhea by keeping a record of the time, frequency,
length, and quantity of bleeding. She should also tell
the doctor about any recent illnesses, including longstanding conditions like diabetes mellitus. The doctor
may also inquire about the patient’s diet, exercise
patterns, sexual activity, contraceptive use, current
medications, or past surgical procedures.
The doctor will then perform a physical examination to evaluate the patient’s weight in proportion to
her height, to check for signs of normal sexual development, to make sure the heart rhythm and other vital
signs are normal, and to palpate (feel) the thyroid
gland for evidence of swelling.
In the case of female athletes, the doctor may need
to establish a relationship of trust with the patient
before asking about such matters as diet, practice
and workout schedules, and the use of such drugs as
steroids or ephedrine. The presence of stress fractures
in young women should be investigated. In some cases,
the doctor may give the patients the Eating Disorder
Inventory (EDI) or a similar screening questionnaire
to help determine whether the patient is at risk for
developing anorexia or bulimia.
Laboratory tests
After taking the woman’s history, the gynecologist
or family practitioner does a pelvic examination and
Pap test. To rule out specific causes of oligomenorrhea,
the doctor may also do a pregnancy test and blood tests
to check the level of thyroid hormone. Based on the
initial test results, the doctor may want to do tests to
determine the level of other hormones that play a role in
reproduction.
As of 2003, more sensitive monoclonal assays
have been developed for measuring hormone levels in
the blood serum of women with PCOS, thus allowing
earlier and more accurate diagnosis.
Imaging studies
In some cases the doctor may order an ultrasound
study of the pelvic region to check for anatomical
abnormalities, or x rays or a bone scan to check for
bone fractures. In a few cases the doctor may order an
GALE ENCYCLOPEDIA OF MEDICINE

MRI to rule out tumors affecting the hypothalamus or
pituitary gland.

Treatment
Treatment of oligomenorrhea depends on the
cause. In adolescents and women near menopause,
oligomenorrhea usually needs no treatment. For
some athletes, changes in training routines and eating
habits may be enough to return the woman to a
regular menstrual cycle.
Most patients suffering from oligomenorrhea are
treated with birth control pills. Other women, including those with PCOS, are treated with hormones.
Prescribed hormones depend on which particular
hormones are deficient or out of balance. When oligomenorrhea is associated with an eating disorder or
the female athlete triad, the underlying condition
must be treated. Consultation with a psychiatrist and
nutritionist is usually necessary to manage an eating
disorder. Female athletes may require physical therapy or rehabilitation as well.

Alternative treatment
As with conventional medicial treatments, alternative treatments are based on the cause of the condition.
If a hormonal imbalance is revealed by laboratory
testing, hormone replacements that are more ‘‘natural’’
for the body (including tri-estrogen and natural progesterone) are recommended. Glandular therapy can assist
in bringing about a balance in the glands involved in
the reproductive cycle, including the hypothalmus,
pituitary, thyroid, ovarian, and adrenal glands. Since
homeopathy and acupuncture work on deep, energetic
levels to rebalance the body, these two modalities may
be helpful in treating oligomenorrhea. Western and
Chinese herbal medicines also can be very effective.
Herbs used to treat oligomenorrhea include dong quai
(Angelica sinensis), black cohosh (Cimicifuga racemosa),
and chaste tree (Vitex agnus-castus). Herbal preparations used to bring on the menstrual period are known
as emmenagogues. For some women, meditation, guided
imagery, and visualization can play a key role in the
treatment of oligomenorrhea by relieving emotional
stress.
Diet and adequate nutrition, including adequate
protein, essential fatty acids, whole grains, and fresh
fruits and vegetables, are important for every woman,
especially if deficiencies are present or if she regularly
exercises very strenuously. Female athletes at the high
school or college level should consult a nutritionist to
make sure that they are eating a well-balanced diet
2673

Oligomenorrhea

Diagnosis

Oligomenorrhea

KEY TERMS
Anorexia nervosa—A disorder of the mind and
body in which people starve themselves in a desire
to be thin, despite being of normal or below normal
body weight for their size and age.
Cyst—An abnormal sac containing fluid or semisolid material.
Emmenagogue—A medication or herbal preparation given to bring on a woman’s menstrual period.
Female athlete triad—A combination of disorders
frequently found in female athletes that includes
disordered eating, osteoporosis, and oligo- or amenorrhea. The triad was first officially named in 1993.
Osteoporosis—The excessive loss of calcium from
the bones, causing the bones to become fragile and
break easily. Women who are not menstruating are
especially vulnerable to this condition because
estrogen, a hormone that protects bones against
calcium loss, decreases drastically after menopause.

that is adequate to maintain a healthy weight for their
height. Girls participating in dance or in sports that
emphasize weight control or a slender body type (gymnastics, track and field, swimming, and cheerleading)
are at higher risk of developing eating disorders than
those that are involved in such sports as softball,
weight lifting, or basketball. In some cases the athlete
may be given calcium or vitamin D supplements to
lower the risk of osteoporosis.
Many women, including those with PCOS, are
successfully treated with hormones for oligomenorrhea.
They have more frequent periods and begin ovulating
during their menstrual cycle, restoring their fertility.
For women who do not respond to hormones or
who continue to have an underlying condition that
causes oligomenorrhea, the outlook is less positive.
Women who have oligomenorrhea may have difficulty
conceiving children and may receive fertility drugs.
The absence of adequate estrogen increases risk for
bone loss (osteoporosis) and cardiovascular disease.
Women who do not have regular periods also are more
likely to develop uterine cancer. Oligomenorrhea can
become amenorrhea at any time, increasing the chance
of having these complications.

from maintaining a regular menstrual cycle. Adequate
nutrition and a less vigorous training schedules
will normally prevent oligomenorrhea. When oligomenorrhea is caused by hormonal factors, it is not
preventable, but it is often treatable.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, D.C.: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Menstrual Abnormalities and Abnormal Uterine
Bleeding.’’ Section 18, Chapter 235 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Menstrual Symptoms, Menopause, and PMS.’’ New
York: Simon & Schuster, 2002.
PERIODICALS

Barrow, Boone, MD. ‘‘Female Athlete Triad.’’ eMedicine
June 17, 2004. <http://www.emedicine.com/sports/
topic163.htm>.
Chandran, Latha, MBBS, MPH. ‘‘Menstruation Disorders.’’
eMedicine August 9, 2004. <http://www.emedicine.com/
ped/topic2781.htm>.
Hopkinson, R. A., and J. Lock. ‘‘Athletics, Perfectionism,
and Disordered Eating.’’ Eating and Weight Disorders
9 (June 2004): 99–106.
Klentrou, P., and M. Plyley. ‘‘Onset of Puberty, Menstrual
Frequency, and Body Fat in Elite Rhythmic Gymnasts
Compared with Normal Controls.’’ British Journal of
Sports Medicine 37 (December 2003): 490–494.
Milsom, S. R., M. C. Sowter, M. A. Carter, et al. ‘‘LH Levels
in Women with Polycystic Ovarian Syndrome: Have
Modern Assays Made Them Irrelevant?’’ BJOG 110
(August 2003): 760–764.
Nelson, Lawrence M., MD, Vladimir Bakalov, MD, and
Carmen Pastor, MD. ‘‘Amenorrhea.’’ eMedicine
August 9, 2004. <http://www.emedicine.com/med/
topic117.htm>.
Suliman, A. M., T. P. Smith, J. Gibney, and T. J. McKenna.
‘‘Frequent Misdiagnosis and Mismanagement of
Hyperprolactinemic Patients Before the Introduction of
Macroprolactin Screening: Application of a New Strict
Laboratory Definition of Macroprolactinemia.’’
Clinical Chemistry 49 (September 2003): 1504–1509.
Webber, L. J., S. Stubbs, J. Stark, et al. ‘‘Formation and
Early Development of Follicles in the Polycystic
Ovary.’’ Lancet 362 (September 27, 2003): 1017–1021.
ORGANIZATIONS

Prevention
Oligomenorrhea is preventable only in women
whose low body fat to weight ratio is keeping them
2674

American Academy of Child and Adolescent Psychiatry.
3615 Wisconsin Avenue, NW, Washington, DC 200163007. (202) 966-7300. Fax: (202) 966-2891. <http://www.
aacap.org>.
GALE ENCYCLOPEDIA OF MEDICINE

OTHER

Clinical Research Bulletin. vol. 1, no. 14. <http://www.
herbsinfo.com>.

Tish Davidson, A.M.
Rebecca J. Frey, Ph.D.

Omega-3 Fatty Acids
Definition
Essential to human health, omega-3 fatty acids are
a form of polyunsaturated fats that are not made by
the body and must be obtained from a person’s food.

Purpose
Eating foods rich in omega-3 fatty acids is part of
a healthy diet and helps people maintain their health.

Description
In recent years, a great deal of attention has been
placed on the value of eating a low fat diet. In some
cases, people have taken this advice to the extreme by
adopting a diet that is far too low in fat or, worse yet,
a diet that has no fat at all. But the truth is that not all
fat is bad. Although it is true that trans and saturated
fats, which are found in high amounts in red meat,
butter, whole milk, and some prepackaged foods,
have been shown to raise a person’s total cholesterol,
polyunsaturated fats can actually play a part in keeping cholesterol low. Two especially good fats are the
omega-3 fatty acids and the omega-6 fatty acids, which
are polyunsaturated.
Two types of omega-3 fatty acids are eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA),
which are found mainly in oily cold-water fish, such as
tuna, salmon, trout, herring, sardines, bass, swordfish,
and mackerel. With the exception of seaweed, most
plants do not contain EPA or DHA. However, alphalinolenic acid (ALA), which is another kind of omega3 fatty acid, is found in dark green leafy vegetables,
flaxseed oil, fish oil, and canola oil, as well as nuts and
GALE ENCYCLOPEDIA OF MEDICINE

beans, such as walnuts and soybeans. Enzymes in a
person’s body can convert ALA to EPA and DHA,
which are the two kinds of omega-3 fatty acids easily
utilized by the body.
Many experts agree that it is important to maintain
a healthy balance between omega-3 fatty acids and
omega-6 fatty acids. As Dr. Penny Kris-Etherton
and her colleagues reported in their article published
in the American Journal of Nutrition an over consumption of omega-6 fatty acids has resulted in an unhealthy
dietary shift in the American diet. The authors point
out that what used to be a 1:1 ratio between omega-3
and omega-6 fatty acids is now estimated to be a 10:1
ratio. This poses a problem, researchers say, because
consuming some of the beneficial effects gained from
omega-3 fatty acids are negated by an over consumption of omega-6 fatty acids. For example, omega-3 fatty
acids have anti-inflammatory properties, whereas
omega-6 fatty acids tend to promote inflammation.
Cereals, whole grain bread, margarine, and vegetable
oils, such as corn, peanut, and sunflower oil, are examples of omega-6 fatty acids. In addition, people consume a lot of omega-6 fatty acid simply by eating the
meat of animals that were fed grain rich in omega-6.
Some experts suggest that eating one to four times
more omega-6 fatty acids than omega-3 fatty acids is
a reasonable ratio. In other words, as dietitians often
say, the key to a healthy diet is moderation and balance.
The health benefits of omega-3 fatty acids
There is strong evidence that omega-3 fatty acids
protect a person against atherosclerosis and therefore
against heart disease and stroke, as well as abnormal
heart rhythms that cause sudden cardiac death,
and possibly autoimmune disorders, such as lupus and
rheumatoid arthritis. In fact, Drs. Dean Ornish and
Mehmet Oz, renowned heart physicians, said in a
2002 article published in O Magazine that the benefits
derived from consuming the proper daily dose of
omega-3 fatty acids may help to reduce sudden cardiac
death by as much as 50%. In fact, in an article
published by American Family Physician, Dr. Maggie
Covington, a clinical assistant professor at the
University of Maryland, also emphasized the value
of omega-3 fatty acids with regard to cardiovascular
health and referred to one of the largest clinical trials
to date, the GISSI-Prevenzione Trial, to illustrate
her point. In the study, 11,324 patients with coronary
heart disease were divided into four groups: one
group received 300 mg of vitamin E, one group received
850 mg of omega-3 fatty acids, one group received the
vitamin E and fatty acids, and one group served as
the control group. After a little more than three years,
2675

Omega-3 Fatty Acids

American College of Sports Medicine (ACSM). 401 West
Michigan Street, Indianapolis, IN 46202-3233. (317)
637-9200. Fax: (317) 634-7817. <http://
www.acsm.org>.
Polycystic Ovarian Syndrome Association. P.O. Box 80517,
Portland, OR 7280. (877) 775-7267. <http://www.
pcosupport.org>.

Omega-3 Fatty Acids

‘‘the group given omega-3 fatty acids only had a 45%
reduction in sudden death and a 20% reduction in
all-cause mortality,’’ as stated by Dr. Covington.
According to the American Heart Association
(AHA), the ways in which omega-3 fatty acids may
reduce cardiovascular disease are still being studied.
However, the AHA indicates that research as shown
that omega-3 fatty acids:


decrease the risk of arrthythmias, which can lead to
sudden cardiac death



decrease triglyceride levels



decrease the growth rate of atherosclerotic plaque



lower blood pressure slightly

In fact, numerous studies show that a diet rich in
omega-3 fatty acids not only lowers bad cholesterol,
known as LDL, but also lowers triglycerides, the fatty
material that circulates in the blood. Interestingly,
researchers have found that the cholesterol levels of
Inuit Eskimos tend to be quite good, despite the fact
that they have a high fat diet. The reason for this,
research has found, is that their diet is high in fatty
fish, which is loaded with omega-3 fatty acids. The
same has often been said about the typical
Mediterranean-style diet.
Said to reduce joint inflammation, omega-3 fatty
acid supplements have been the focus of many studies
attempting to validate its effectiveness in treating
rheumatoid arthritis. According to a large body of
research in the area, omega-3 fatty acid supplements
are clearly effective in reducing the symptoms associated with rheumatoid arthritis, such as joint tenderness and stiffness. In some cases, a reduction in the
amount of medication needed by rheumatoid arthritis
patients has been noted.
More research needs to be done to substantiate
the effectiveness of omega-3 fatty acids in treating
eating disorders, attention deficit disorder, and
depression. Some studies have indicated, for example,
that children with behavioral problems and attention
deficit disorder have lower than normal amounts of
omega-3 fatty acids in their bodies. However, until
there is more data in these very important areas of
research, a conservative approach should be taken,
especially when making changes to a child’s diet.
Parents should to talk to their child’s pediatrician to
ascertain if adding more omega-3 fatty acids to their
child’s diet is appropriate. In addition, parents should
take special care to avoid feeding their children fish
high in mercury. A food list containing items rich in
omega-3 fatty acids can be obtained from a licensed
dietitian.
2676

Mercury levels and concerns about safety
A great deal of media attention has been focused
on the high mercury levels found in some types of
fish. People concerned about fish consumption and
mercury levels can review public releases on the subject issued by the U. S. Food and Drug Administration
and the Environmental Protection Agency. Special
precautions exist for children and pregnant or breastfeeding women. They are advised to avoid shark,
mackerel, swordfish, and tilefish. However, both the
U.S. Food and Drug Administration and the Environmental Protection Agency emphasis the importance of dietary fish. Fish, they caution, should not be
eliminated from the diet. In fact, Robert Oh, M.D.,
stated in his 2005 article, which was published in The
Journal of the American Board of Family Practice
‘‘with the potential health benefits of fish, women of
childbearing age should be encouraged to eat 1 to 2
low-mercury fish meals per week.’’
Contaminants and concerns about safety
Other concerns regarding fish safety have also
been reported. In 2004, Hites and colleagues assessed
organic contaminants in salmon in an article published in Science. Their conclusion that farmed salmon
had higher concentrations of polychlorinated biphenyls than wild salmon prompted public concerns and a
response from the American Cancer Society. Farmed
fish in Europe was found to have higher levels of
mercury than farmed salmon in North and South
America; however, the American Cancer Society
reminded the public that the ‘‘levels of toxins Hites
and his colleagues found in the farmed salmon were
still below what the U.S. Food and Drug
Administration, which regulates food, considers
hazardous.’’ The American Cancer Society still continues to promote a healthy, varied diet, which
includes fish as a food source.

Recommended dosage
The AHA recommends that people eat two servings of fish, such as tuna or salmon, at least twice a
week. A person with coronary heart disease, according
to the AHA, should consume 1 gram of omega-3 fatty
acids daily through food intake, most preferably
through the consumption of fatty fish. The AHA
also states that ‘‘people with elevated triglycerides
may need 2 to 4 grams of EPA and DHA per day
provided as a supplement,’’ which is available in liquid
or capsule form. Ground or cracked flaxseed can
easily be incorporated into a person’s diet by sprinkling it over salads, soup, and cereal.
GALE ENCYCLOPEDIA OF MEDICINE



3 ounces of pickled herring = 1.2 grams of omega-3
fatty acids



3 ounces of salmon = 1.3 grams of omega-3 fatty acids



3 ounces of halibut = 1.0 grams of omega-3 fatty acids



3 ounces of mackerel = 1.6 grams of omega-3 fatty
acids



1 1/2 teaspoons of flaxseeds = 3 grams of omega-3
fatty acids

Precautions
In early 2004, the U.S. Food and Drug
Administration along with the the Environmental
Protection Agency issued a statement that women
who are or may be pregnant, as well as breastfeeding
mothers and children, should avoid eating some types
of fish thought to contain high levels of mercury. Fish
that typically contain high levels of mercury are shark,
swordfish, and mackerel, whereas shrimp, canned
light tuna, salmon, and catfish are generally thought
to have low levels of mercury. Because many people
engage in fishing as a hobby, women should be sure
before they eat any fish caught by friends and family
that the local stream or lake is considered low in
mercury.
Conflicting information exists whether it is safe for
patients with macular degeneration to take omega-3
fatty acids in supplement form. Until more data
becomes available, it is better for people with macular
degeneration to receive their omega-3 fatty acids from
the food they eat.

Side effects
Fish oil supplements can cause diarrhea and gas.
Also, the fish oil capsules tend to have a fishy
aftertaste.

Interactions
Although there are no significant drug interactions associated with eating foods containing omega3 fatty acids, patients who are being treated with
blood-thinning medications should not take omega3 fatty acid supplements without seeking the advice
of their physicians. Excessive bleeding could result.
For the same reason, some patients who plan to take
more than 3 grams of omega-3 fatty acids in supplement form should first seek the approval of their
physicians.
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

Albert, C. M., Hennekens, C. H., O’Donnell, C. J., et al.
‘‘Fish consumption and risk of sudden cardiac death.’’
Journal of the American Medical Association 279 (1998):
23–28.
Covington, M. B. ‘‘Omega-3 fatty acids.’’ American Family
Physician 70 (2004): 133–140.
Harris, W. S. ‘‘N-3 fatty acids and serum lipoproteins:
human studies.’’ American Journal of Clinical Nutrition
65 (1997): 1645–1654.
Hites, R. A., Foran, J. A., Carpenter, D. O., et al. ‘‘Global
assessment of organic contaminants in farmed salmon.’’
Science 303 (1997): 226–229.
Kris-Etherton, P. M., Harris, W. S., Appel, L. J., and
American Heart Association Nutrition Committee.
‘‘Fish consumption, fish oil, omega-3 fatty acids, and
cardiovascular disease.’’ Circulation 106 (2003):
2747–2757.
Kris-Etherton, P. M., Taylor, D. S., Yu-Poth, S., et al.
‘‘Polyunsaturated fatty acids in the food chain in the
United States. ’’ American Journal of Clinical Nutrition
71 (2000): 1795–1885.
Oh, R. ‘‘Practical applications of fish oil (omega-3 fatty
acids) in primary.’’ The Journal of the American Board
of Family Practice 18 (2005): 28–36.
Ornish, Dean, and Oz, Mehmet. ‘‘Caution: Strong at
Heart.’’ O: The Oprah Magazine November
2002:163–168.
ORGANIZATION

American Cancer Society. ‘‘Is Salmon Safe?’’ American
Cancer Society 28 Jan 2004 American Cancer Society.
24 Feb 2005 <http://www.cancer.org/>.
American Heart Association. ‘‘American Heart Association
Recommendation: Fish and Omega-3 Fatty Acids.’’
American Heart Association 2005 American Heart
Association. 22 Feb 2005 <http://www.americanheart.
org/>.
Health and Age. ‘‘Omega-3 Fatty Acids.’’ Health and Age
2005 [cited 22 Feb 2005]. <http://www.healthandage.
com/html/res/com/ConsSupplements/
Omega3FattyAcidscs.html>.
Kris-Etherton, P. M., Harris, W. S., Appel, L. J., and
American Heart Association Nutrition Committee.
‘‘American Heart Association Statement: New
Guidelines Focus on Fish, Fish Oil, Omega-3 Fatty
Acids.’’ American Heart Association 18 November 2002
American Heart Association. 22 Feb 2005 <http://
www.americanheart.org/>.
U.S. Food and Drug Administration. ‘‘What You Need to
Know About Mercury in Fish and Shellfish.’’ U.S. Food
and Drug Administration. March 2004 U.S. Food and
Drug Administration. 22 Feb 2005 <http://www.cfsan.
fda.gov/~dms/admehg3.html>.

Lee Ann Paradise
2677

Omega-3 Fatty Acids

Sources differ, but here are some general
examples:

Onychomycosis

Omeprazole see Antiulcer drugs
Omphalocele see Abdominal wall defects
Onchocerciasis see Filariasis

Onychomycosis
Definition
Onychomycosis is a fungal infection of the fingernails or toenails. The actual infection is of the bed of
the nail and of the plate under the surface of the nail.

Description
Onychomycosis is the most common of all diseases of the nails in adults. In North America, the
incidence falls roughly between 2–13%. The incidence
of onychomycosis is also greater in older adults, and
up to 90% of the elderly may be affected. Men are
more commonly infected than women.
Individuals who are especially susceptible include
those with chronic diseases such as diabetes and circulatory problems and those with diseases that suppress
the immune system. Other risk factors include a family
history, previous trauma to the nails, warm climate,
and occlusive or tight footwear.

Causes and symptoms
Onychomycosis is caused by three types of fungi,
called dermatophytes, yeasts, and nondermatophyte
molds. Fungi are simple parasitic plant organisms that
do not need sunlight to grow. Toenails are especially
susceptible because fungi prefer dark damp places.
Swimming pools, locker rooms, and showers typically
harbor fungi. Chronic diseases such as diabetes, problems with the circulatory system, or immune deficiency
disease are risk factors. A history of athlete’s foot and
excess perspiration are also risk factors.
Onychomycosis can be present for years without
causing pain or disturbing symptoms. Typically, the
nail becomes thicker and changes to a yellowishbrown. Foul smelling debris may collect under the
nail. The infection can spread to the surrounding
nails and even the skin.

Diagnosis
To make a diagnosis of onychomycosis, the clinician must collect a specimen of the nail in which
2678

infection is suspected. A clipping is taken from the
nail plate, and a sample of the debris from underneath
the nail bed is also taken, usually with a sharp curette.
Debris from the nail surface may also be taken. These
will be sent for microscopic analysis to a laboratory,
as well as cultured to determine what types of fungus
are growing there.

Treatment
Onychomycosis is very difficult and sometimes
impossible to treat, and therapy is often long-term.
Therapy consists of topical treatments that are applied
directly to the nails, as well as two systemic drugs,
griseofulvin and ketoconazole. Topical therapy is
reserved for only the mildest cases. The use of griseofulvin and ketoconazole is problematic, and there are
typically high relapse rates of 50–85%. In addition,
treatment must be continued for a long duration
(10–18 months for toenails), with monthly laboratory
monitoring for several side effects, including liver toxicity. Individuals taking these medications must also
abstain from alcohol consumption.
In the past few years, newer oral antifungal agents
have been developed, and include itraconazole
(Sporanox), terbinafine (Lamisil), and fluconazole
(Diflucan). These agents, when taken orally for as
little as 12 weeks, bring about better cure rates and
fewer side effects than either griseofulvin or ketoconazole. The most common side effect is stomach upset.
Patients taking oral antifungal therapy must have
a complete blood count and liver enzyme workup
every four to six weeks. Terbinafine in particular has
markedly less toxicity to the liver, one of the more
severe side effects of the older agents, griseofulvin
and ketoconazole.
Treatment should be continued until microscopic
exam or culture shows no more fungal infection. Nails
may, however, continue to look damaged even after a
clinical cure is achieved. Nails may take up to a full
year to return to normal. If the nail growth slows or
stops, additional doses of antifungal therapy should
be taken.
Nail debridement is another treatment option, but
it is considered by many to be primitive compared with
topical or systemic treatment. Clinicians perform nail
debridement in their offices. The nail is cut and then
thinned using surgical tools or chemicals, and then the
loose debris under the nail is removed. The procedure
is painless, and often improves the appearance of
the nails immediately. In addition, it helps whatever
medication being used to penetrate the newly thinned
nail. Patients with very thickened nails will sometimes
GALE ENCYCLOPEDIA OF MEDICINE

Curette—Spoon-shaped instrument for removing
debris, growths, or infected nail matter.
Dermatophytes, yeasts, and nondermatophyte
molds—Three types of fungi responsible for fungal
infections of the nails.

undergo chemical removal of a nail. A combination of
oral, topical, and surgical removal can increase the
chances of curing the infection.

Alternative treatment
For controlling onychomycosis, as opposed to
curing it, some experts advocate using Lotrimin
cream, available over the counter. The cream should
be thoroughly rubbed into the nail daily in order to
control the infection.
In general, nutrition may also play a role in
promoting good nail health and thus preventing nail
disease. Adequate protein and minerals, in the form of
nuts, seeds, whole grains, legumes, fresh vegetables,
and fish, should be consumed. Sugars, alcohol, and
caffeine should be avoided. Certain supplements may
also be beneficial, including vitamin A (10,000 IU per
day), zinc (15–30 mg per day), iron (ferrous glycinate
100 mg per day, vitamin B12 (1,000 mcg per day), and
essential fatty acids in the form of flax, borage, or
evening primrose oil (1,000–1,5000 mg twice daily).
Herbal remedies may also relieve some of the
symptoms of onychomycosis. A combination of coneflower, oregano, spilanthes, usnea, Oregon grape root,
and myrrh can be used as a tincture (20 drops four
times daily).
Undiluted grapefruit seed extract and tea tree oil
are also said to be beneficial when applied topically to
the infected nails.

range from 25–40%, and those with fluconazole,
which was recently approved in the United States,
have not been documented by long-term trials

Prevention
Keeping the feet clean and dry, and washing with
soap and water and drying thoroughly are important
preventive steps to take to prevent onychomycosis.
Other preventive measures include keeping the nails
cut short and wearing shower shoes whenever walking
or showering in public places. Daily changes of shoes,
socks, or hosiery are also helpful. Excessively tight hose
or shoes promote moisture, which in turn, provides a
wonderful environment for onychomycotic infections.
To prevent this, individuals should wear only socks
made of synthetic fibers, which can absorb moisture
more quickly than those made of cotton or wools.
Manicure and pedicure tools should be disinfected
after each use. Finally, nail polish should not be applied
to nails that are infected, as this causes the water or
moisture that collects under the surface of the nail to
not evaporate and be trapped.
Resources
PERIODICALS

Harrell T. K., et al. ‘‘Onychomycosis: Improved Cure Rates
withItraconazole and Terbinafine.’’ Journal of the
American Board of Family Practitioners July-August
2001: 268- 73.
Scher Robert K. ‘‘Novel Treatment Strategies for Superficial
Mycoses.’’ Journal of the American Academy of
Dermatology 1999.
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, PO Box 4014, Schaumburg, IL 60168-4014. (847)
330-0230. Fax: (847) 330-0050. <http://www.aad.org>.
OTHER

<http://www.emedicine.com/derm/topic200.htm>.
<http://www.nailfungus.org/about.html>.

Liz Meszaros

Prognosis
Onychomycosis is typically quite difficult to cure
completely. Even if a clinical cure is achieved after long
therapy with either topical or oral drugs, normal
regrowth takes four to six months in the fingernails,
and eight to 12 months in the toenails, which grow more
slowly. Relapse is common, and often, the nail or nail
bed is permanently damaged. For toenails infected with
onychomycosis, terbinafine seems to offer the highest
cure rate (35–50%). Itraconazole cure rates typically
GALE ENCYCLOPEDIA OF MEDICINE

Oophorectomy
Definition
Oophorectomy is the surgical removal of one or
both ovaries. It is also called ovariectomy or ovarian
ablation. If one ovary is removed, a woman may continue to menstruate and have children. If both ovaries
2679

Oophorectomy

KEY TERMS

Oophorectomy

are removed, menstruation stops and a woman loses the
ability to have children.

Purpose
Oophorectomy is performed to:


remove cancerous ovaries



remove the source of estrogen that stimulates some
cancers



remove large ovarian cysts in women with polycystic
ovarian syndrome (PCOS)



excise an abscess



treat endometriosis



lower the risk of an ectopic pregnancy



lower the risk of cancer in a woman with a family
history of ovarian or breast cancer

In an oophorectomy, one or a portion of one ovary
may be removed or both ovaries may be removed.
When oophorectomy is done to treat ovarian cancer
or other spreading cancers, both ovaries are always
removed. This is called a bilateral oophorectomy.
Oophorectomies are sometimes performed on premenopausal women who have estrogen-sensitive breast
cancer in an effort to remove the main source of estrogen from their bodies. This procedure has become less
common than it was in the 1990s. Today, chemotherapy
drugs are available that alter the production of estrogen
and tamoxifen blocks any of the effects any remaining
estrogen may have on cancer cells.
In younger women with low-grade or earlystage ovarian tumors who have not yet completed
their families, the surgeon may perform a unilateral
oophorectomy. This approach is called fertility-saving
or fertility-sparing surgery. Women who are appropriate candidates for this type of oophorectomy do not
have higher rates of cancer recurrence than women
who have both ovaries removed.
Until the 1980s, women over age 40 having
hysterectomies (surgical removal of the uterus) routinely had healthy ovaries and fallopian tubes removed
at the same time. This operation is called a bilateral
salpingo-oophorectomy. Many physicians reasoned that
a woman over 40 was approaching menopause and
soon her ovaries would stop secreting estrogen and
releasing eggs. Removing the ovaries would eliminate
the risk of ovarian cancer and only accelerate menopause by a few years.
In the 1990s, the thinking about routine oophorectomy began to change. The risk of ovarian cancer in
women who have no family history of the disease
2680

is less than 1%. Meanwhile, removing the ovaries
increases the risk of cardiovascular disease and accelerates osteoporosis unless a woman takes prescribed
hormone replacements. In addition, other studies
indicate that a bilateral oophorectomy increases a
woman’s risk of developing thyroid cancer. Women
with mild endometriosis can often be successfully
treated with birth control pills or other hormone
medications without having to undergo surgery.
Under certain circumstances, oophorectomy may
still be the treatment of choice to prevent breast and
ovarian cancer in certain high-risk women. A study
done at the University of Pennsylvania and released
in 2000 showed that healthy women who carried
the BRCA1 or BRCA2 genetic mutations that predisposed them to breast cancer had their risk of breast
cancer drop from 80% to 19% when their ovaries were
removed before age 40. Women between the ages of 40
and 50 showed less risk reduction, and there was no
significant reduction of breast cancer risk in women
over age 50.
Overall, ovarian cancer still ranks low on a
woman’s list of health concerns: It accounts for only
4% of all cancers in women. But the lifetime risk
for developing ovarian cancer in women who have
mutations in BRCA1 is significantly increased over
the general population and may cause an ovarian
cancer risk of 30% by age 60. For women at increased
risk, oophorectomy may be considered after the age of
35 if childbearing is complete.
The value of ovary removal in preventing both
breast and ovarian cancer has been documented.
However, there are disagreements within the medical
community about when and at what age this treatment
should be offered. Preventative oophorectomy, called
preventative bilateral oophorectomy (PBO), is not
always covered by insurance. One study conducted in
2000 at the University of California at San Francisco
found that only 20% of insurers paid for PBO.
Another 25% had a policy against paying for the
operation, and the remaining 55% said that they
would decide about payment on an individual basis.

Precautions
There are situations in which oophorectomy is a
medically wise choice for women who have a family
history of breast or ovarian cancer. However, women
with healthy ovaries who are undergoing hysterectomy
for reasons other than cancer should discuss with their
doctors the benefits and disadvantages of having their
ovaries removed at the time of the hysterectomy. It is
important for women to ask questions about the longGALE ENCYCLOPEDIA OF MEDICINE

Description
Oophorectomy is done under general anesthesia.
It is performed through the same type of incision,
either vertical or horizontal, as an abdominal hysterectomy. Horizontal incisions leave a less noticeable
scar, but vertical incisions give the surgeon a better
view of the abdominal cavity.
After the incision is made, the abdominal muscles
are pulled apart, not cut, so that the surgeon can see
the ovaries. Then the ovaries, and often the fallopian
tubes, are removed.
Oophorectomy can sometimes be done with a
laparoscopic procedure. With this surgery, a tube containing a tiny lens and light source is inserted through
a small incision in the navel. A camera can be attached
that allows the surgeon to see the abdominal cavity
on a video monitor. When the ovaries are detached,
they are removed though a small incision at the top of
the vagina. The ovaries can also be cut into smaller
sections and removed.
The advantages of abdominal incision are that the
ovaries can be removed even if a woman has many
adhesions from previous surgery. The surgeon gets a
good view of the abdominal cavity and can check the
surrounding tissue for disease. A vertical abdominal
incision is mandatory if cancer is suspected. The disadvantages are that bleeding is more likely to be a
complication of this type of operation. The operation
is more painful than a laparoscopic operation and the
recovery period is longer. A woman can expect to be
in the hospital two to five days and will need three to
six weeks to return to normal activities.

Preparation
Before surgery, the doctor will order blood and
urine tests, and any additional tests such as ultrasound
or x rays to help the surgeon visualize the woman’s
condition. The woman may also meet with the anesthesiologist to evaluate any special conditions that might
affect the administration of anesthesia. A colon preparation may be done, if extensive surgery is anticipated.
On the evening before the operation, the woman
should eat a light dinner, then take nothing by mouth,
including water or other liquids, after midnight.
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
After surgery a woman will feel some discomfort.
The degree of discomfort varies and is generally greatest with abdominal incisions, because the abdominal
muscles must be stretched out of the way so that the
surgeon can reach the ovaries.
When both ovaries are removed, women who do
not have cancer are started on hormone replacement
therapy to ease the symptoms of menopause that occur
because estrogen produced by the ovaries is no longer
present. If even part of one ovary remains, it will
produce enough estrogen that a woman will continue
to menstruate, unless her uterus was removed in a
hysterectomy. Antibiotics are given to reduce the risk
of post-surgery infection.
Return to normal activities takes anywhere from
two to six weeks, depending on the type of surgery.
When women have cancer, chemotherapy or radiation
are often given in addition to surgery. Some women
have emotional trauma following an oophorectomy,
and can benefit from counseling and support groups.

Risks
Oophorectomy is a relatively safe operation,
although, like all major surgery, it does carry some
risks. These include unanticipated reaction to anesthesia, internal bleeding, blood clots, accidental damage
to other organs, and post-surgery infection.
Complications after an oophorectomy include
changes in sex drive, hot flashes, and other symptoms
of menopause if both ovaries are removed. Women
who have both ovaries removed and who do not take
estrogen replacement therapy run an increased risk for
cardiovascular disease and osteoporosis. Women with
a history of psychological and emotional problems
before an oophorectomy are more likely to experience
psychological difficulties after the operation.

Normal results
If the surgery is successful, the ovaries will be
removed without complication, and the underlying
problem resolved. In the case of cancer, all the cancer
will be removed.

Abnormal results
Complications may arise if the surgeon finds that
cancer has spread to other places in the abdomen.
If the cancer cannot be removed by surgery, it must
be treated with chemotherapy and radiation.
2681

Oophorectomy

term risks of a bilateral oophorectomy; one study
published in 2003 reported that many women awaiting
surgery felt that they did not have adequate information about their treatment options and were unaware
of the possible long-term consequences to health.

Ophthalmoplegia

KEY TERMS
Cyst—An abnormal sac containing fluid or semisolid material.
Ectopic pregnancy—A pregnancy that develops
when a fertilized egg implants outside the uterus,
usually in the Fallopian tubes, but sometimes in the
ovary itself.
Endometriosis—A benign condition that occurs
when cells from the lining of the uterus begin growing outside the uterus.
Fallopian tubes—Slender tubes that carry ova from
the ovaries to the uterus.
Hysterectomy—Surgical removal of the uterus.
Osteoporosis—The excessive loss of calcium from
the bones, causing the bones to become fragile and
break easily.
Polycystic ovarian syndrome (PCOS)—A condition in which the eggs are not released from the
ovaries and instead form multiple cysts.

Ovarian remnant syndrome is a complication
that results in about 18% of women who have had
an oophorectomy for severe endometriosis. The syndrome is characterized by chronic pelvic pain and/or
a pelvic mass; it is treated by further surgery to
remove the remaining ovarian tissue.
Resources

Bhavnani, V., and A. Clarke. ‘‘Women Awaiting
Hysterectomy: A Qualitative Study of Issues Involved
in Decisions About Oophorectomy.’’ BJOG 110
(February 2003): 168–174.
Bleiker, E. M., D. E. Hahn, and N. K. Aaronson.
‘‘Psychosocial Issues in Cancer Genetics—Current
Status and Future Directions.’’ Acta Oncologica 42
(2003): 276–286.
de Carvalho, M., J. Jenkins, M. Nehrebecky, and L. Lahl.
‘‘The Role of Estrogens in BRCA1/2 Mutation
Carriers: Reflections on the Past, Issues for the
Future.’’ Cancer Nursing 26 (December 2003): 421–430.
Itoh, H., A. Ishihara, H. Koita, et al. ‘‘Ovarian Pregnancy:
Report of Four Cases and Review of the Literature.’’
Pathology International 53 (November 2003): 806–809.
Lane, G. ‘‘Prophylactic Oophorectomy: Why and When?’’
Journal of the British Menopause Society 9 (December
2003): 156–160.
Sainsbury, R. ‘‘Ovarian Ablation as a Treatment for Breast
Cancer.’’ Surgical Oncology 12 (December 2003):
241–250.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800)ACS-2345. <http://www.cancer.org>.
American College of Obstetricians and Gynecologists
(ACOG). 409 12th Street, SW, P. O. Box 96920,
Washington, DC 20090-6920. <http://www.acog.org>.
National Cancer Institute (NCI). Public Inquiries Office,
Suite 3036A, 6116 Executive Blvd., MSC 8322,
Bethesda, MD 20892-8322. (800) 4-CANCER.
<http://www.nci.nih.gov>.
OTHER

Ovarian Cancer Home Page, National Cancer Institute.
<http://www.nci.nih.gov/cancer_information/
cancer_type/ovarian/>.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Endometriosis.’’ Section 18, Chapter 239. In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Ovarian Cancer.’’ Section 18, Chapter 241. In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Cancer.’’ New York: Simon & Schuster, 2002.
PERIODICALS

Abu-Rafeh, B., G. A. Vilos, and M. Misra. ‘‘Frequency and
Laparoscopic Management of Ovarian Remnant
Syndrome.’’ Journal of the American Association of
Gynecologic Laparoscopists 10 (February 2003): 33–37.
Ayhan, A., H. Celik, C. Tskiran, et al. ‘‘Oncologic and
Reproductive Outcome After Fertility-Saving Surgery
in Ovarian Cancer’’ European Journal of Gynaecological
Oncology 24 (March 2003): 223–232.
2682

Tish Davidson, A.M.
Rebecca J. Frey, Ph.D.

Open fracture reduction see Fracture repair
Ophthalmic antibiotics see Antibiotics,
ophthalmic

Ophthalmoplegia
Definition
Ophthalmoplegia is a paralysis or weakness of one
or more of the muscles that control eye movement.
The condition can be caused by any of several neurologic disorders. It may be myopathic, meaning that
the muscles controlling eye movement are directly
involved, or neurogenic, meaning that the nerve
GALE ENCYCLOPEDIA OF MEDICINE

Description
Because the eyes do not move together in
ophthalmoplegia, patients may complain of double
vision. Double vision is especially troublesome if the
ophthalmoplegia comes on suddenly or affects each
eye differently. Because ophthalmoplegia is caused
by another, underlying disease, it is often associated
with other neurologic symptoms, including limb
weakness, lack of coordination, and numbness.

Causes and symptoms
Ocular myopathy is also known as mitochondrial
encephalomyelopathy with ophthalmoplegia or progressive external ophthalmoplegia. Because it is so
often associated with diseases affecting many levels
of the neurologic system, it is often referred to as
‘‘ophthalmoplegia plus.’’ The main feature is progressive limitation of eye movements, usually with drooping of the eyelids (ptosis). Ptosis may occur years
before other symptoms of ophthalmoplegia. Because
both eyes are equally involved and because ability
to move the eyes lessens gradually over the course
of years, double vision is rare. On examination, the
eyelids may appear thin. This disease usually begins in
childhood or adolescence but may start later.
When ophthalmoplegia is caused by muscle degeneration (myopathic), muscle biopsy, in which a small
piece of muscle is surgically removed and examined
microscopically, will find characteristic abnormal
muscle fibers called ragged red fibers. In this form of
ophthalmoplegia, the patient may experience weakness
of the face, the muscles involved in swallowing, the
neck, or the limbs.
Progressive external ophthalmoplegia is sometimes associated with specific neurologic syndromes.
These syndromes include familial forms of spastic
paraplegia, spinocerebellar disorders, or sensorimotor
peripheral neuropathy. Kearns-Sayre syndrome causes
ophthalmoplegia along with loss of pigment in the
retina, the light-sensitive membrane lining the eye. In
addition, the disease may cause heart block that must
be corrected with a pacemaker, increased protein in
the cerebrospinal fluid, and a progressively disabling
lack of muscular coordination (cerebellar syndrome).
Symptoms of the disease appear before age 15.
GALE ENCYCLOPEDIA OF MEDICINE

Some of the progressive external ophthalmoplegia
syndromes are unusual in that inheritance is controlled by DNA in the mitochondria. The mitochondria are rod-shaped structures within a cell that
convert food to usable energy. Most inherited diseases
are passed on by DNA in the cell nucleus, the core that
contains the hereditary material. Mitochondrial
inheritance tends to be passed on by the mother.
Other forms of progressive external ophthalmoplegia
are not inherited but occur sporadically with no clear
family history. It is not known why some forms are
neurogenic and others are myopathic. In the forms
inherited through mitochondrial DNA, it is not
known which gene product is affected.
Internuclear ophthalmoplegia in multiple sclerosis is caused by damage to a bundle of fibers in the
brainstem called the medial longitudinal fasciculus.
In this syndrome, the eye on the same side as the
damaged medial longitudinal fasciculus is unable to
look outward (that is, the left eye cannot look left).
The other eye exhibits jerking movements (nystagmus)
when the patient tries to look left. Internuclear
ophthalmoplegia may be seen rarely without multiple
sclerosis in patients with certain types of cancer or with
Chiari type II malformation.
Eye movement disorders and ophthalmoplegia
can also be seen with progressive supranuclear palsy,
thyroid disease, diabetes mellitus, brainstem tumors,
migraine, basilar artery stroke, pituitary stroke,
myasthenia gravis, muscular dystrophy, and the Fisher
variant of Guillain-Barré syndrome. A tumor or aneurysm in the cavernous sinus, located behind the eyes, can
cause painful ophthalmoplegia. Painful ophthalmoplegia can also be caused by an inflammatory process in
the same area, called Tolosa-Hunt syndrome.

Diagnosis
The patient’s medical and family history and the
examination findings will usually help differentiate
the various syndromes associated with ophthalmoplegia. In addition, each syndrome is associated with
characteristic features, such as nystagmus or ptosis.
All patients with progressive external ophthalmoplegia should have a muscle biopsy to look for ragged
red fibers or changes suggesting muscular dystrophy.
A sample should be sent for analysis of mitochondrial
DNA. Electromyogram (EMG), measurement of
electrical activity in the muscle, helps diagnose
myopathy.
Computed tomography scan (CT scan) or magnetic
resonance imaging (MRI) scans of the brain may be
needed to rule out brain tumor, stroke, aneurysm, or
2683

Ophthalmoplegia

pathways controlling eye muscles are affected.
Diseases associated with ophthalmoplegia are ocular
myopathy, which affects muscles, and internuclear
ophthalmoplegia, a disorder caused by multiple sclerosis, a disease which affects nerves.

Oppositional defiant disorder

Prognosis

KEY TERMS
Cerebellar—Involving the cerebellum, which controls walking, balance, and coordination.
Cerebrospinal fluid—Fluid bathing the brain and
spinal cord.
Heart block—A problem with electrical conduction in the heart muscle that may lead to irregular
heart beat and require a pacemaker for treatment.
Mitochondria—Spherical or rod shaped parts of
the cell. Mitochondria contain genetic material
(DNA and RNA) and are responsible for converting
food to energy.

The prognosis of progressive external ophthalmoplegia depends on the associated neurological problems;
in particular, whether there is severe limb weakness
or cerebellar symptoms that may be mild or disabling.
As with most chronic neurologic diseases, mortality
increases with disability. Progressive external ophthalmoplegia itself is not a life-threatening condition.
Kearns-Sayre syndrome is disabling, probably shortens
the life span, and few if any patients have children.
Overall life expectancy for multiple sclerosis patients
is seven years less than normal; death rates are higher
for women than for men.

Prevention
There is no way to prevent ophthalmoplegia.
multiple sclerosis. When multiple sclerosis is suspected,
evoked potential testing of nerve response may
also be helpful. Analysis of cerebrospinal fluid may
show changes characteristic of multiple sclerosis or
Kearns-Sayre syndrome. Other tests that may be
helpful in Kearns-Sayre include electrocardiogram
(measuring electrical activity of the heart muscles),
retinal examination, and a hearing test (audiogram).
For possible myasthenia gravis, the Tensilon (edrophonium) test should be done. Tests should also be
done to measure activity of the cell-surface receptors
for acetylcholine, a chemical that helps pass electrical
impulses along nerve cells in the muscles. Thyroid
disease and diabetes mellitus should be excluded by
appropriate blood work.

Resources
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave.,
St. Paul, MN 55116. (612) 695-1940. <http://
www.aan. com>.

Laurie Barclay, MD

Ophthalmoscopic examination see Eye
examination
Opiate withdrawal see Withdrawal
syndromes
Opioid analgesics see Analgesics, opioid

Treatment
There are no specific cures for ocular myopathy
or progressive external ophthalmoplegia. Vitamin E
therapy has been used to treat Kearns-Sayre syndrome. Coenzyme Q (ubiquinone), a naturally occurring substance similar to vitamin K, is widely used to
treat other forms of progressive external ophthalmoplegia, but the degree of success varies. Specific treatments are available for multiple sclerosis, myasthenia
gravis, diabetes mellitus, and thyroid disease.
Symptoms of ophthalmoplegia can be relieved by
mechanical treatment. Surgical procedures can lift
drooping eyelids or a patch over one eye can be used
to relieve double vision. Because there is no blink
response, a surgically lifted eyelid exposes the cornea
of the eye so that it may become dry or be scratched.
These complications must be avoided by using artificial tears and wearing eyepatches at night. In KearnsSayre syndrome, a pacemaker may be needed.
2684

Oppositional defiant disorder
Definition
Oppositional defiant disorder (ODD) is defined
by the Diagnostic and Statistical Manual of Mental
Disorders, fourth edition (DSM-IV), as a recurring
pattern of negative, hostile, disobedient, and defiant
behavior in a child or adolescent, lasting for at least
six months without serious violation of the basic
rights of others. The incidence of ODD in the
American population varies somewhat according to
the sample studied; DSM-IV gives the rate as between
2–16% while the American Academy of Child and
Adolescent Psychiatry (AACAP) gives a figure of
5%–15%, and a researcher at a children’s hospital
gives a rate of 6–10%.
GALE ENCYCLOPEDIA OF MEDICINE

In order to meet DSM-IV criteria for ODD, the
behavior disturbances must cause clinically significant
problems in social, school, or work functioning. The
course of oppositional defiant disorder varies among
patients. In males, the disorder is more common
among those who had problem temperaments or
high motor activity in the preschool years. During
the school years, patients may have low self-esteem,
changing moods, and a low frustration tolerance.
Patients may swear and use alcohol, tobacco, or illicit
drugs at an early age. There are frequent conflicts with
parents, teachers, and peers.
Children with this disorder show their negative
and defiant behaviors by being persistently stubborn
and resisting directions. They may be unwilling to
compromise, give in, or negotiate with adults.
Patients may deliberately or persistently test limits,
ignore orders, argue, and fail to accept blame for
misdeeds. Hostility is directed at adults or peers and
is shown by verbal aggression or deliberately annoying
others.

Causes and symptoms
Oppositional defiant disorder is more common in
boys than girls before puberty; the disorder typically
begins by age eight. After puberty the male:female ratio
is about 1:1. Although the specific causes of the disorder are unknown, parents who are overly concerned
with power and control may cause an eruption to occur.
Symptoms often appear at home, but over time may
appear in other settings as well. Usually the disorder
occurs gradually over months or years. Several theories
about the causes of oppositional defiant disorder are
being investigated. Oppositional defiant disorder may
be related to:


the child’s temperament and the family’s response to
that temperament



an inherited predisposition to the disorder in some
families



marital discord or violence between husband and
wife



frequent or multiple geographical moves



a neurological cause, like a head injury



a chemical imbalance in the brain (especially with
the brain chemical serotonin)

Oppositional defiant disorder appears to be more
common in families where at least one parent has
a history of a mood disorder, conduct disorder,
attention deficit/hyperactivity disorder, antisocial
GALE ENCYCLOPEDIA OF MEDICINE

personality disorder, or a substance-related disorder.
Additionally, some studies suggest that mothers
with a depressive disorder are more likely to have
children with oppositional behavior. However, it is
unclear to what extent the mother’s depression
results from or causes oppositional behavior in
children.
Symptoms include a pattern of negative, hostile,
and defiant behavior lasting at least six months. During
this time four or more specific behaviors must be
present. These behaviors include the child who:


often loses his/her temper



often argues with adults



often actively defies or refuses to comply with adults’
requests or rules



often deliberately annoys people



often blames others for his/her mistakes or
misbehavior



is often touchy or easily annoyed by others



is often angry and resentful



is often spiteful or vindictive



misbehaves



swears or uses obscene language



has a low opinion of him/herself

The diagnosis of oppositional defiant disorder
is not made if the symptoms occur exclusively in
psychotic or mood disorders. Criteria are not met for
conduct disorder, and, if the child is 18 years old or
older, criteria are not met for antisocial personality
disorder. In other words, a child with oppositional
defiant disorder does not show serious aggressive
behaviors or exhibit the physical cruelty that is
common in other disorders.
Additional problems may be present, including:


learning problems



a depressed mood



hyperactivity (although attention deficit/hyperactivity
disorder must be ruled out)



substance abuse or dependence



dramatic and erratic behavior

The patient with oppositional defiant disorder is
moody, easily frustrated, and may abuse drugs.

Diagnosis
While psychological testing may be needed, the
doctor must examine and talk with the child, talk
2685

Oppositional defiant disorder

Description

Oppositional defiant disorder

with the parents, and review the medical history.
Diagnosis is complicated because oppositional defiant
disorder rarely travels alone. Children with attention/
deficit hyperactive disorder will also have oppositional defiant disorder 50% of the time. Children
with depression/anxiety will have oppositional defiant disorder 10–29% of the time. Because all of the
features of this disorder are usually present in conduct
disorder, oppositional defiant disorder is not diagnosed
if the criteria are met for conduct disorder.
A diagnosis of oppositional defiant disorder
should be considered only if the behaviors occur
more frequently and have more serious consequences
than is typically observed in other children of a similar
developmental stage. Further, the behavior must
lead to significant impairment in social, school, or
work functioning.
As of 2004 a new evaluation scale known as the
Oppositional Defiant Behavior Inventory (ODBI) has
been developed as an aid to diagnosis. The ODBI
appears to meet accepted standards of reliability and
validity.

Treatment
Treatment of oppositional defiant disorder
usually consists of group, individual and/or family
therapy, and education. Of these, individual therapy
is the most common. Therapy can provide a consistent
daily schedule, support, consistent rules, discipline,
and limits. It can also help train patients to get along
with others and modify behaviors. Therapy can occur
in residential, day treatment, or medical settings.
Additionally, having a healthy role model as an
example is important for the patient.
Parent management training focuses on teaching
the parents specific and more effective techniques for
handling the child’s opposition and defiance.
Research has shown that parent management training
is more effective than family therapy. One variation of
parent management training known as Parent-Child
Interaction Therapy (PCIT) appears to be helpful over
the long term; a group of Australian researchers
reported in 2004 that families who were given a course
of PCIT maintained their gains two years after the
program ended.
As of the early 2000s, elementary school teachers
are being trained to deal more effectively with classroom disruptions caused by children with ODD. The
long-term effectiveness of these interventions, however, will require further study.
Whether involved in therapy or working on this
disorder at home, the patient must work with his or
2686

KEY TERMS
Attention deficit/hyperactivity disorder—A persistent pattern of inattention, hyperactivity and/or
impulsiveness; the pattern is more frequent and
severe than is typically observed in people at a
similar level of development.
Conduct disorder—A repetitive and persistent
pattern of behavior in which the basic rights of
others are violated or major age-appropriate rules
of society are broken.

her parents’ guidance to make the fullest possible
recovery. According to the New York Hospital/
Cornell Medical Center, the patients must:


use self timeouts



identify what increases anxiety



talk about feelings instead of acting on them



find and use ways to calm themselves



frequently remind themselves of their goals



get involved in tasks and physical activities that
provide a healthy outlet for energy



learn how to talk with others



develop a predictable, consistent, daily schedule of
activity



develop ways to obtain pleasure and feel good



learn how to get along with other people



find ways to limit stimulation



learn to admit mistakes in a matter-of-fact way

Stimulant medication is used only when oppositional defiant disorder coexists with attention deficit/
hyperactivity disorder. Currently, no research is
currently available on the use of other psychiatric
medications in the treatment of oppositional defiant
disorder.

Prognosis
The outcome varies. In some children the disorder
evolves into a conduct disorder or a mood disorder.
Later in life, oppositional defiant disorder can develop
into passive aggressive personality disorder or antisocial personality disorder. Some children respond well
to treatment and some do not. Generally, with treatment, reasonable adjustment in social settings and in
the workplace can be made in adulthood.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, D.C.: American Psychiatric Association,
2000.
PERIODICALS

Harada, Y., K. Saitoh, J. Iida, et al. ‘‘The Reliability and
Validity of the Oppositional Defiant Behavior
Inventory.’’ European Child and Adolescent Psychiatry
13 (June 2004): 185–190.
Nixon, R. D., L. Sweeney, D. B. Erickson, and S. W. Touyz.
‘‘Parent-Child Interaction Therapy: One- and TwoYear Follow-Up of Standard and Abbreviated
Treatments for Oppositional Preschoolers.’’ Journal
of Abnormal Child Psychology 32 (June 2004): 263–271.
Tynan, W. Douglas, PhD. ‘‘Oppositional Defiant
Disorder.’’ eMedicine November 2, 2003. <http://
www.emedicine.com/ped/topic2791.htm>.
van Leer, P. A., B. O. Muthen, R. M. van der Sar, and
A. A. Crijnen. ‘‘Preventing Disruptive Behavior in
Elementary Schoolchildren: Impact of a Universal
Classroom-Based Intervention.’’ Journal of Consulting
and Clinical Psychology 72 (June 2004): 467–478.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry
(AACAP). 3615 Wisconsin Avenue, NW, Washington,
DC 20016-3007. (202) 966-7300. Fax: (202) 966-2891.
<http://www.aacap.org>.
American Psychiatric Association. 1400 K Street, NW,
Washington, DC 20005. <http://www.psych.org>.
Families Anonymous. Westchester County, Westchester,
NY. (212) 354-8525.
OTHER

American Academy of Child and Adolescent Psychiatry
(AACAP). Children with Oppositional Defiant Disorder.
AACAP Facts for Families #72. Washington, DC:
AACAP, 2000.

optic neuritis, Leber’s hereditary optic atrophy, toxic
or nutritional optic neuropathy, glaucoma, vascular
disorders, trauma, and other systemic disorders.

Description
The process of vision involves light entering the eye
and triggering chemical changes in the retina, a pigmented layer lining the back of the eye. Nerve impulses
created by this process travel to the brain via the optic
nerve. Using a hand-held instrument called an ophthalmoscope, the doctor can see the optic nerve head (optic
disc) which is the part of the optic nerve that enters
at the back of the eyeball. In optic atrophy, the disc is
pale and has fewer blood vessels than normal.

Causes and symptoms
Symptoms of optic atrophy are a change in the
optic disc and a decrease in visual function. This
change in visual function can be a decrease in sharpness and clarity of vision (visual acuity) or decreases
in side (peripheral) vision. Color vision and contrast
sensitivity can also be affected.
There are many possible causes of optic atrophy.
The causes can range from trauma to systemic disorders. Some possible causes of optic atrophy include:


Optic neuritis. Optic neuritis is an inflammation of the
optic nerve. It may be associated with eye pain worsened by eye movement. It is more common in young
to middle-aged women. Some patients with optic
neuritis may develop multiple sclerosis later on in life.



Leber’s hereditary optic neuropathy. This is a disease
of young men (late teens, early 20s), characterized by
an onset over a few weeks of painless, severe, central
visual loss in one eye, followed weeks or months later
by the same process in the other eye. At first the optic
disc may be slightly swollen, but eventually there is
optic atrophy. The visual loss is generally permanent.
This condition is hereditary. If a patient knows that
Leber’s runs in the family, genetic counseling should
be considered.



Toxic optic neuropathy. Nutritional deficiencies and
poisons can be associated with gradual vision loss
and optic atrophy, or with sudden vision loss and
optic disc swelling. Toxic and nutritional optic neuropathies are uncommon in the United States, but took
on epidemic proportions in Cuba in 1992–1993. The
most common toxic optic neuropathy is known as
tobacco-alcohol amblyopia, thought to be caused by
exposure to cyanide from tobacco smoking, and by
low levels of vitamin B12 because of poor nutrition and
poor absorption associated with drinking alcohol.

David James Doermann
Rebecca Frey, PhD

Optic atrophy
Definition
Optic atrophy can be defined as damage to the
optic nerve resulting in a degeneration or destruction
of the optic nerve. Optic atrophy may also be referred
to as optic nerve head pallor because of the pale
appearance of the optic nerve head as seen at the back
of the eye. Possible causes of optic atrophy include:
GALE ENCYCLOPEDIA OF MEDICINE

2687

Optic atrophy

Resources

Optic atrophy

Other possible toxins included ethambutol, methyl
alcohol (moonshine), ethylene glycol (antifreeze), cyanide, lead, and carbon monoxide. Certain medications
have also been implicated. Nutritional optic neuropathy may be caused by deficiencies of protein, or of the
B vitamins and folate, associated with starvation,
malabsorption, or alcoholism.




Glaucoma. Glaucoma may be caused by an increase
of pressure inside the eye. This increased pressure
may eventually affect the optic nerve if left untreated.
Compressive optic neuropathy. This is the result
of a tumor or other lesion putting pressure on the
optic nerve. Another possible cause is enlargement
of muscles involved in eye movement seen in
hyperthyroidism (Graves’ disease).



Retinitis pigmentosa. This is a hereditary ocular
disorder.



Syphilis. Left untreated, this disease may result in
optic atrophy.

Diagnosis
Diagnosis involves recognizing the characteristic
changes in the optic disc with an ophthalmoscope, and
measuring visual acuity, usually with an eye chart.
Visual field testing can test peripheral vision. Color
vision and contrast sensitivity can also be tested.
Family history is important in the diagnosis of inherited conditions. Exposure to poisons, drugs, and even
medications should be determined. Suspected poisoning can be confirmed through blood and urine analysis, as can vitamin deficiency.
Brain magnetic resonance imaging (MRI) may show
a tumor or other structure putting pressure on the optic
nerve, or may show plaques characteristic of multiple
sclerosis, which is frequently associated with optic
neuritis. However, similar MRI lesions may appear in
Leber’s hereditary optic neuropathy. Mitochondrial
DNA testing can be done on a blood sample, and can
identify the mutation responsible for Leber’s.
Visual evoked potentials (VEP), which measure
speed of conduction over the nerve pathways involved
in sight, may detect abnormalities in the clinically
unaffected eye in early cases of Leber’s. Fluorescein
angiography gives more detail about blood vessels in
the retina.

Treatment
Treatment of optic neuritis with steroids is controversial. As of mid-1998, there is no known treatment for Leber’s hereditary optic neuropathy.
2688

KEY TERMS
Atrophy—A destruction or dying of cells, tissues, or
organs.
Cerebellar—Involving the part of the brain (cerebellum), which controls walking, balance, and
coordination.
Mitochondia—A structure in the cell responsible for
producing energy. A defect in the DNA in the mitochondria is involved in Leber’s optic neuropathy.
Neuritis—An inflammation of the nerves.
Neuropathy—A disturbance of the nerves, not
caused by an inflammation. For example, the
cause may be toxins, or unknown.

Treatment of other causes of optic atrophy varies
depending upon the underlying disease.

Prognosis
Many patients with optic neuritis eventually
develop multiple sclerosis. Most patients have a
gradual recovery of vision after a single episode of
optic neuritis, even without treatment. Prognosis
for visual improvement in Leber’s hereditary optic
neuropathy is poor, with the specific rate highly
dependent on which mitochondrial DNA mutation is
present. If the cause of toxic or nutritional deficiency
optic neuropathy can be found and treated early,
such as stopping smoking and taking vitamins in
tobacco-alcohol amblyopia, vision generally returns
to near normal over several months’ time. However,
visual loss is often permanent in cases of long-standing
toxic or nutritional deficiency optic neuropathy.

Prevention
People noticing a decrease in vision (central and/
or side vision) should ask their eye care practitioner
for a check up. Patients should also go for regular
vision exams. Patients should ask their doctor how
often that should be, as certain conditons may warrant
more frequent exams. Early detection of inflammations or other problems lessens the chance of developing optic atrophy.
As of mid 1998, there are no preventive measures
that can definitely abort Leber’s hereditary optic neuropathy in those genetically at risk, or in those at risk
based on earlier involvement of one eye. However,
some doctors recommend that their patients take
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave.,
St. Paul, MN 55116. (612) 695-1940. <http://www.aan
.com>.
Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://www
.preventblindness.org>.

Laurie Barclay, MD



blind spots, particularly with central vision



pain with eye movement



headache



sudden color blindness



impaired night vision



impaired contrast sensitivity

Optic neuritis

vitamin C, vitamin E, coenzyme Q10, or other antioxidants, and that they avoid the use of tobacco or
alcohol. Patients should ask their doctors about the
use of vitamins. Avoiding toxin exposure and nutritional deficiency should prevent toxic or nutritional
deficiency optic neuropathy.

Optic neuritis is most commonly associated with
multiple sclerosis (MS). Other causes include viral
or fungal infections, encephalomyelitis, autoimmune
diseases, or pressure on the nerve from tumors or
vascular diseases (i.e., temporal arteritis). Some toxins,
such as methanol and lead, can also damage the optic
nerve, as can long-term abuse of alcohol and tobacco.
Patients with non-MS related optic neuritis are usually
immunocompromised in some way.

Diagnosis

Optic neuritis
Definition
Optic neuritis is a vision disorder characterized by
inflammation of the optic nerve.

Description
Optic neuritis occurs when the optic nerve, the
pathway that transmits visual information to the
brain, becomes inflamed and the myelin sheath that
surrounds the nerve is destroyed (a process known
as demyelination). It typically occurs in one eye at a
time (70%), and the resulting vision loss is rapid and
progressive, but only temporary. Thirty percent of
patients experience occurrence in both eyes. Optic
neuritis tends to afflict young adults with an average
age in their 30s. Seventy-five percent of patients with
optic neuritis are women.
Nerve damage that occurs in the section of the optic
nerve located behind the eyeball, is called retrobulbar
neuritis, and is most often associated with multiple
sclerosis. Optic nerve inflammation and edema (swelling) caused by intracranial pressure at the place where
the nerve enters the eyeball is termed papillitis.

Causes and symptoms
Symptoms of optic neuritis include one or more of
the following:


blurred or dimmed vision

GALE ENCYCLOPEDIA OF MEDICINE

An ophthalmologist, a physician trained in diseases of the eye, will typically make a diagnosis of
optic neuritis. A complete visual exam, including a
visual acuity test, color vision test, and examination
of the retina and optic disc with an ophthalmoscope,
will be performed. Clinical signs such as impaired
pupil response may be apparent during an eye
exam, but in some cases the eye may appear normal.
A medical history will also be performed to determine
if exposure to toxins such as lead may have caused the
optic neuritis.
Further diagnostic testing such as magnetic resonance imaging (MRI) may be necessary to confirm a
diagnosis of optic neuritis. An MRI can also reveal
signs of multiple sclerosis.

Treatment
Treatment of optic neuritis depends on the
underlying cause of the condition. Vision loss resulting from a viral condition usually resolves itself once
the virus is treated, and optic neuritis resulting from
toxin damage may improve once the source of the
toxin is removed.
A course of intravenous corticosteroids (steroids)
followed by oral steroids has been found to be helpful
in restoring vision quickly to patients with MS-related
episodes of optic neuritis, but its efficacy in preventing
relapse is debatable. The Optic Neuritis Treatment
Trial (ONTT) has shown that IV steroids may be
effective in reducing the onset of MS for up to two
years, but further studies are necessary. Oral prednisone has been found to increase the likelihood of
2689

Oral contraceptives

ORGANIZATIONS

KEY TERMS
Atrophy—Cell wasting or death.
Multiple sclerosis—An autoimmune disease of the
central nervous system characterized by damage to
the myelin sheath that covers nerves.
Temporal arteritis—Also known as giant cell arteritis. Inflammation of the large arteries located in
the temples which is marked by the presence of
giant cells and symptoms of headache and facial
pain.
Visual acuity test—An eye examination that
determines sharpness of vision, typically performed by identifying objects and/or letters on an
eye chart.

recurrent episodes of optic neuritis, and is not recommended for treating the disorder.

Prognosis
The vision loss associated with optic neuritis is
usually temporary. Spontaneous remission occurs in
two to eight weeks. Sixty-five to eighty percent of
patients can expect 20/30 or better vision after recovery.
Long-term prognosis depends on the underlying cause
of the condition. If a viral infection has triggered the
episode, it frequently resolves itself with no after effects.
If optic neuritis is associated with multiple sclerosis,
future episodes are not uncommon. Thirty-three percent of optic neuritis cases recur within five years. Each
recurrence results in less recovery and worsening vision.
There is a strong association between optic neuritis and
MS. In those without multiple sclerosis, half who
experience an episode of vision loss related to optic
neuritis will develop the disease within 15 years.

Prevention
Regular annual eye exams are critical to maintaining healthy vision. Early treatment of vision problems
can prevent permanent optic nerve damage (atrophy).
Resources
BOOKS

Leitman, Mark. Manual for Eye Examination and Diagnosis.
5th ed. Boston: Blackwell Science, 2001.
PERIODICALS

Cohen, Joyce Render, et al. ‘‘Living with Low Vision.’’Inside
MS 1 (2001): 46.
2690

Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://www
.prevent-blindness.org>.

Paula Anne Ford-Martin

Oral cancer see Head and neck cancer
Oral cholecystography see Gallbladder x rays

Oral contraceptives
Definition
Oral contraceptives are medicines taken by mouth
to help prevent pregnancy. They are also known as the
Pill, OCs, or birth control pills.

Purpose
Oral contraceptives, also known as birth control
pills, contain artificially made forms of two hormones
produced naturally in the body. These hormones,
estrogen and progestin, regulate a woman’s menstrual
cycle. When taken in the proper amounts, following a
specific schedule, oral contraceptives are very effective
in preventing pregnancy. Studies show that less than
one of every one hundred women who use oral contraceptives correctly becomes pregnant during the first
year of use.
These pills have several effects that help prevent
pregnancy. For pregnancy to occur, an egg must
become mature inside a woman’s ovary, be released,
and travel to the fallopian tube. A male sperm must also
reach the fallopian tube, where it fertilizes the egg. Then
the fertilized egg must travel to the woman’s uterus
(womb), where it lodges in the uterus lining and develops into a fetus. The main way that oral contraceptives
prevent pregnancy is by keeping an egg from ripening
fully. Eggs that do not ripen fully cannot be fertilized.
In addition, birth control pills thicken mucus in the
woman’s body through which the sperm has to swim.
This makes it more difficult for the sperm to reach the
egg. Oral contraceptives also change the uterine lining
so that a fertilized egg cannot lodge there to develop.
Birth control pills may cause good or bad side
effects. For example, a woman’s menstrual periods
are regular and usually lighter when she is taking
oral contraceptives, and the pills may reduce the risk
of ovarian cysts, breast lumps, pelvic inflammatory
disease, and other medical problems. However, taking
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
No form of birth control (except not having sex) is
100% effective. However, oral contraceptives can be
highly effective when used properly. Discuss the
options with a health care professional.
Oral contraceptives do not protect against AIDS
or other sexually transmitted diseases. For protection
against such diseases, use a latex condom.
Oral contraceptives are not effective immediately
after a woman begins taking them. Physicians recommend using other forms of birth control for the first
1–3 weeks. Follow the instructions of the physician
who prescribed the medicine.
Smoking cigarettes while taking oral contraceptives greatly increases the risk of serious side effects.
Women who take oral contraceptives should not smoke
cigarettes.
Seeing a physician regularly while taking this
medicine is very important. The physician will note
unwanted side effects. Follow his or her advice on how
often you should be seen.
Anyone taking oral contraceptives should be sure
to tell the health care professional in charge before
having any surgical or dental procedures, laboratory
tests, or emergency treatment.
This medicine may increase sensitivity to sunlight.
Women using oral contraceptives should avoid too
much sun exposure and should not use tanning beds,
tanning booths, or sunlamps until they know how
the medicine affects them. Some women taking oral
contraceptives may get brown splotches on exposed
areas of their skin. These usually go away over time
after the women stop taking birth control pills.
Oral contraceptives may cause the gums to
become tender and swollen or to bleed. Careful brushing and flossing, gum massage, and regular cleaning
may help prevent this problem. Check with a physician
or dentist if gum problems develop.
GALE ENCYCLOPEDIA OF MEDICINE

Women who have certain medical conditions
or who are taking certain other medicines may have
problems if they take oral contraceptives. Before
taking these drugs, be sure to let the physician know
about any of these conditions:
ALLERGIES. Anyone who has had unusual reactions to estrogens or progestins in the past should let
her physician know before taking oral contraceptives.
The physician should also be told about any allergies
to foods, dyes, preservatives, or other substances.
PREGNANCY. Women who become pregnant or
think they may have become pregnant while taking
birth control pills should stop taking them immediately and check with their physicians. Women who
want to start taking oral contraceptives again after
pregnancy should not refill their old prescriptions
without checking with their physicians. The physician
may need to change the prescription.
BREASTFEEDING. Women who are breastfeeding
should check with their physicians before using oral
contraceptives. The hormones in the pills may reduce
the amount of breast milk and may cause other problems in breastfeeding. They may also cause jaundice
and enlarged breasts in nursing babies whose mothers
take the medicine.
OTHER MEDICAL CONDITIONS. Oral contraceptives
may improve or worsen some medical conditions.
The possibility that they may make a condition
worse does not necessarily mean they cannot be
used. In some cases, women may need only to be
tested or followed more closely for medical problems
while using oral contraceptives. Before using oral
contraceptives, women with any of these medical
problems should make sure their physicians are
aware of their conditions:


Female conditions such as menstrual problems,
endometriosis, or fibroid tumors of the uterus. Birth
control pills usually make these problems better, but
may sometimes make them worse or more difficult to
diagnose.



Heart or circulation problems; recent or past blood
clots or stroke. Women who already have these
problems may be at greater risk of developing
blood clots or circulation problems if they use oral
contraceptives. However, healthy women who do not
smoke may lower their risk of circulation problems
and heart disease by taking the pills.



Breast cysts, lumps, or other noncancerous breast
problems. Oral contraceptives generally protect
against these conditions, but physicians may recommend more frequent breast exams for women taking
the pills.
2691

Oral contraceptives

birth control pills increases the risk of heart attack,
stroke, and blood clots in certain women. Serious side
effects such as these are more likely in women over
35 years of age who smoke cigarettes and in those with
specific health problems such as high blood pressure,
diabetes, or a history of breast or uterine cancer.
A woman who wants to use oral contraceptives should
ask her physician for the latest information on the
risks and benefits of all types of birth control and
should consider her age, health, and medical history
when deciding what to use.

Oral contraceptives



Breast cancer or other cancer (now or in the past, or
family history). Oral contraceptives may make some
existing cancers worse. Women with a family history
of breast cancer may need more frequent screening
for the disease if they decide to take birth control
pills.



Migraine headaches. This condition may improve or
may get worse with the use of birth control pills.



Diabetes. Blood sugar levels may increase slightly
when oral contraceptives are used. Usually this
increase is not enough to affect the amount of diabetes
medicine needed. However, blood sugar will need to
be monitored closely while taking oral contraceptives.



Depression. This condition may worsen in women
who already have it or may (rarely) occur again in
women who were depressed in the past.



Gallbladder disease, gallstones, high blood cholesterol, or chorea gravidarum (a nervous disorder).
Oral contraceptives may make these conditions worse.



Epilepsy, high blood pressure, heart or circulation
problems. By increasing fluid build-up, oral contraceptives may make these conditions worse.

Description
Oral contraceptives (birth control pills) come in a
wide range of estrogen-progestin combinations. The
pills in use today contain much lower doses of estrogen
than those available in the past, and this change has
reduced the likelihood of serious side effects. Some
pills contain only progestin. These are prescribed
mainly for women who need to avoid estrogens and
may not be as effective in preventing pregnancy as the
estrogen-progestin combinations.
These medicines come in tablet form, in containers designed to help women keep track of which tablet
to take each day. The tablets are different colors,
indicating amounts of hormones they contain. Some
may contain no hormones at all. These are included
simply to help women stay in the habit of taking a pill
every day, as the hormone combination needs to be
taken only on certain days of the menstrual cycle.
Keeping the tablets in their original container and
taking them exactly on schedule is very important.
They will not be as effective if they are taken in the
wrong order or if doses are missed.
Oral contraceptives are available only with a
physician’s prescription. Some commonly used brands
are Demulen, Desogen, Loestrin, Lo/Ovral, Nordette,
Ortho-Novum, Ortho-Tri-Cyclen, Estrostep, Orthocept, Alesse, Levlite and Ovcon.
2692

The dose schedule depends on the type of oral
contraceptive. The two basic schedules are a 21-day
schedule and a 28-day schedule. On the 21-day
schedule, take one tablet a day for 21 days, then skip
7 days and repeat the cycle. On the 28-day schedule,
take one tablet a day for 28 days; then repeat the cycle.
Be sure to carefully follow the instructions provided
with the medicine. For additional information or
explanations, check with the physician who prescribed
the medicine or the pharmacist who filled the
prescription.
Taking doses more than 24 hours apart may
increase the chance of side effects or pregnancy. Try
to take the medicine at the same time every day. Take
care not to run out of pills. If possible, keep an extra
month’s supply on hand and replace it every month
with the most recently filled prescription.
Try not to miss a dose, as this increases the risk of
pregnancy. If a dose is missed, follow the package
directions or check with the physician who prescribed
the medicine for instructions. It may be necessary to
use another form of birth control for some time after
missing a dose.
Taking this medicine with food or at bedtime will
help prevent nausea, a side effect that sometimes
occurs during the first few weeks. This side effect
usually goes away as the body adjusts to the medicine.
Taking oral contraceptives may have several benefits outside of their ability to prevent pregnancy.
Research indicates that with 10 to 12 years of oral
contraceptive use, a woman’s risk of ovarian cancer
is reduced by up to 80 %. There may also be an
approximate 50% decrease in the rate of endometrial
cancers in women. One other well-known, noncontraceptive benefit of oral contraceptives is an improvement in acne. The combination oral contraceptive
ethinyl estradiol/norgestimate has been approved by
the Food and Drug Administration for the treatment
of acne. Another positive effect of oral contraceptive
use is improvement in abnormal uterine bleeding.
Older women may also benefit from using oral contraceptives, because the pills can increase bone mass as
women enter their menopausal years, when osteoporosis is a growing concern.
Oral contraceptives may also be used on an emergency basis as a means of preventing pregnancy in
women who have had unprotected intercourse. Two
products specifically designed for this purpose are
Preven and Plan B. In 2001, the American College
of Obstetricians and Gynecologists (ACOG) recommended that emergency oral contraceptives be available as an over-the-counter medicine. The Food and
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Taking oral contraceptives with certain other
drugs may affect the way the drugs work or may
increase the chance of side effects.
Side Effects
Serious side effects are rare in healthy women who
do not smoke cigarettes. In women with certain health
problems, however, oral contraceptives may cause
problems such as liver cancer, noncancerous liver
tumors, blood clots, or stroke. Health care professionals can help women weigh the benefits of being
protected against unwanted pregnancy against the
risks of possible health problems.
The most common minor side effects are nausea;
vomiting; abdominal cramping or bloating; breast
pain, tenderness or swelling; swollen ankles or feet;
tiredness; and acne. These problems usually go away
as the body adjusts to the drug and do not need
medical attention unless they continue or they interfere with normal activities.

months after stopping this medicine should check
with their physicians.
Other rare side effects may occur. Anyone who
has unusual symptoms while taking oral contraceptives should get in touch with her physician.
Interactions
Oral contraceptives may interact with a number of
other medicines. When this happens, the effects of one
or both of the drugs may change or the risk of side
effects may be greater. Anyone who takes oral contraceptives should let the physician know all other medicines she is taking and should ask whether the possible
interactions can interfere with drug therapy.
These drugs may make oral contraceptives less
effective in preventing pregnancy. Anyone who takes
these drugs should use an additional birth control
method for the entire cycle in which the medicine
is used:


ampicillin



penicillin V



rifampin (Rifadin)



tetracyclines

Other side effects should be brought to the attention of the physician who prescribed the medicine.
Check with the physician as soon as possible if any
of the following side effects occur:



griseofulvin (Gris-PEG, Fulvicin)



corticosteroids



barbiturates

menstrual changes, such as lighter periods or missed
periods, longer periods, or bleeding or spotting
between periods



carbamazepine (Tegretol)



phenytoin (Dilantin)



primidone (Mysoline)



ritonavir (Norvir)





headaches



vaginal infection, itching, or irritation



increased blood pressure

Women who have any of the following symptoms
should get emergency help right away. These symptoms may be signs of blood clots:

In addition, taking these medicines with oral contraceptives may increase the risk of side effects or
interfere with the medicine’s effects:


theophylline–effects of this medicine may increase,
along with the chance of unwanted side effects



sudden changes in vision, speech, breathing, or
coordination



cyclosporine–effects of this medicine may increase,
along with the chance of unwanted side effects



severe or sudden headache





coughing up blood



sudden, severe, or continuing pain in the abdomen or
stomach

troleandomycin (TAO)–chance of liver problems
may increase. Effectiveness of oral contraceptive
may also decrease, raising the risk of pregnancy



pain in the chest, groin, or leg (especially in the calf)



weakness, numbness, or pain in an arm or leg

Oral contraceptives may continue to affect the
menstrual cycle for some time after a woman stops
taking them. Women who miss periods for several
GALE ENCYCLOPEDIA OF MEDICINE

The list above does not include every drug that
may interact with oral contraceptives. Be sure to check
with a physician or pharmacist before combining oral
contraceptives with any other prescription or nonprescription (over-the-counter) medicine.
As with any medication, the benefits and risks
should be discussed with a physician.
2693

Oral contraceptives

Drug Administration, however, has not yet approved
any measures that would allow this to happen.

Oral hygiene

OTHER

KEY TERMS
Cyst—An abnormal sac or enclosed cavity in the
body, filled with liquid or partially solid material.
Endometriosis—A condition in which tissue like
that normally found in the lining of the uterus is
present outside the uterus. The condition often
causes pain and bleeding.
Fallopian tube—One of a pair of slender tubes that
extend from each ovary to the uterus. Eggs pass
through the fallopian tubes to reach the uterus.
Fetus—A developing baby inside the womb.
Fibroid tumor—A noncancerous tumor formed of
fibrous tissue.
Hormone—A substance that is produced in one
part of the body, then travels through the bloodstream to another part of the body where it has its
effect.
Jaundice—Yellowing of the eyes and skin due to
the build up of a bile pigment (bilirubin) in the
blood.
Migraine—A throbbing headache that usually
affects only one side of the head. Nausea, vomiting,
increased sensitivity to light, and other symptoms
often accompany migraine.
Mucus—Thick fluid produced by the moist membranes that line many body cavities and structures.
Ovary—A reproductive organ in females that produces eggs and hormones.
Pelvic inflammatory disease—Inflammation of the
female reproductive tract, caused by any of several
microorganisms. Symptoms include severe abdominal pain, high fever, and vaginal discharge. Severe
cases can result in sterility. Also called PID.
Uterus—A hollow organ in a female in which a
fetus develops until birth.

Medline Plus Health Information, U.S. National Library of
Medicine. <http://www.nlm.nih.gov/medlineplus>.

Deanna M. Swartout-Corbeil, R.N.

Oral herpes see Cold sore

Oral hygiene
Definition
Oral hygiene is the practice of keeping the mouth
clean and healthy by brushing and flossing to prevent
tooth decay and gum disease.

Purpose
The purpose of oral hygiene is to prevent the
build-up of plaque, the sticky film of bacteria and
food that forms on the teeth. Plaque adheres to the
crevices and fissures of the teeth and generates acids
that, when not removed on a regular basis, slowly eat
away, or decay, the protective enamel surface of the
teeth, causing holes (cavities) to form. Plaque also
irritates gums and can lead to gum disease (periodontal
disease) and tooth loss. Toothbrushing and flossing
remove plaque from teeth, and antiseptic mouthwashes kill some of the bacteria that help form plaque.
Fluoride—in toothpaste, drinking water, or dental
treatments—also helps to protect teeth by binding
with enamel to make it stronger. In addition to such
daily oral care, regular visits to the dentist promote
oral health. Preventative services that he or she can
perform include fluoride treatments, sealant application, and scaling (scraping off the hardened plaque,
called tartar). The dentist can also perform such diagnostic services as x-ray imaging and oral cancer screening as well as such treatment services as fillings,
crowns, and bridges.

Resources
BOOKS

Beers, Mark H., and Robert Berkow, editors. The Merck
Manual of Diagnosis and Therapy. 17th ed. Whitehouse
Station, NJ: Merck and Company, Inc., 1999.
PERIODICALS

‘‘Current Perspectives on OC Formulations.’’Family
Practice News January 15, 2001: 2.
‘‘Physician Group Supports Safety, Availability of Over-theCounter Emergency Option.’’ Medical Letter on the
CDC and FDA March 18, 2001.

2694

Precautions
Maintaining oral hygiene should be a lifelong
habit. An infant’s gums and, later, teeth should be
kept clean by wiping them with a moist cloth or a
soft toothbrush. However, only a very small amount
(the size of a pea) of toothpaste containing fluoride
should be used since too much fluoride may be toxic to
infants.
An adult who has partial or full dentures should
also maintain good oral hygiene. Bridges and dentures
GALE ENCYCLOPEDIA OF MEDICINE

Brushing and flossing should be performed thoroughly but not too vigorously. Rough mechanical
action may irritate or damage sensitive oral tissues.
Sore or bleeding gums may be experienced for the first
few days after flossing is begun. However, bleeding
continuing beyond one week should be brought to the
attention of a dentist. As a general rule, any sore or
abnormal condition that does not disappear after 10
days should be examined by a dentist.

Description

rubbing motion. At the gumline, the floss is curved
first around one tooth and then the other with gentle
sliding into the space between the tooth and gum. After
each tooth contact is cleaned, a fresh section of floss is
unwrapped from one hand as the used section of floss is
wrapped around the third finger of the opposite hand.
Flossing proceeds between all teeth and behind the last
teeth. Flossing should also be performed around the
abutment (support) teeth of a bridge and under any
artificial teeth using a device called a floss threader.
Dental floss comes in many varieties (waxed,
unwaxed, flavored, tape) and may be chosen on personal preference. For people who have difficulty handling floss, floss holders and other types of interdental
(between the teeth) cleaning aids, such as brushes and
picks, are available.

Brushing
Brushing should be performed with a toothbrush
and a fluoride toothpaste at least twice a day and
preferably after every meal and snack. Effective brushing must clean each outer tooth surface, inner tooth
surface, and the flat chewing surfaces of the back teeth.
To clean the outer and inner surfaces, the toothbrush
should be held at a 45-degree angle against the gums
and moved back and forth in short strokes (no more
than one toothwidth distance). To clean the inside
surfaces of the front teeth, the toothbrush should be
held vertically and the bristles at the tip (called the toe
of the brush) moved gently up and down against each
tooth. To clean the chewing surfaces of the large back
teeth, the brush should be held flat and moved back
and forth. Finally, the tongue should also be brushed
using a back-to-front sweeping motion to remove food
particles and bacteria that may sour the breath.
Toothbrushes wear out and should be replaced
every three months. Consumers should look for toothbrushes with soft, nylon, rounded bristles in a size and
shape that allows them to reach all tooth surfaces easily.
Holding a toothbrush may be difficult for people
with limited use of their hands. The toothbrush handle
may be modified by inserting it into a rubber ball for
easier gripping.
Flossing
Flossing once a day helps prevent gum disease by
removing food particles and plaque at and below the
gumline as well as between teeth. To begin, most of an
18-in (45-cm) strand of floss is wrapped around the
third finger of one hand. A 1-in (2.5-cm) section is then
grasped firmly between the thumb and forefinger of
each hand. The floss is eased between two teeth and
worked gently up and down several times with a
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Negative consequences arise from improper or
infrequent brushing and flossing. The five major oral
health problems are plaque, tartar, gingivitis, periodontitis, and tooth decay.
Plaque is a soft, sticky, colorless bacterial film that
grows on the hard, rough surfaces of teeth. These
bacteria use the sugar and starch from food particles
in the mouth to produce acid. Left to accumulate, this
acid destroys the outer enamel of the tooth, irritates
the gums to the point of bleeding, and produces foul
breath. Plaque starts forming again on teeth four to 12
hours after brushing, so brushing a minimum of twice
a day is necessary for adequate oral hygiene.
When plaque is not regularly removed by brushing and flossing, it hardens into a yellow or brown
mineral deposit called tartar or calculus. This formation is crusty and provides additional rough surfaces
for the growth of plaque. When tartar forms below the
gumline, it can lead to periodontal (gum) disease.
Gingivitis is an early form of periodontal disease,
characterized by inflammation of the gums with painless bleeding during brushing and flossing. This common condition is reversible with proper dental care but
if left untreated, it will progress into a more serious
periodontal disease, periodontitis.
Periodontitis is a gum disease that destroys the
structures supporting the teeth, including bone.
Without support, the teeth will loosen and may fall
out or have to be removed. To diagnose periodontitis,
a dentist looks for gums that are red, swollen, bleeding, and shrinking away from the teeth, leaving widening spaces between teeth and exposed root surfaces
vulnerable to decay.
2695

Oral hygiene

must be kept clean to prevent gum disease. Dentures
should be relined and adjusted by a dentist as necessary to maintain proper fit so the gums do not become
red, swollen, and tender.

Orbital and periorbital cellulitis

Orbital and periorbital
cellulitis

KEY TERMS
Calculus—A hardened yellow or brown mineral
deposit from unremoved plaque; also called tartar.
Cavity—A hole or weak spot in the tooth surface
caused by decay.
Gingivitis—Inflammation of the gums, seen as
painless bleeding during brushing and flossing.
Interdental—Between the teeth.

Definition
Periorbital cellulitis is an inflammation and infection of the eyelid and the skin surrounding the eye.
Orbital cellulitis affects the eye socket (orbit) as well as
the skin closest to it.

Description

Periodontal—Pertaining to the gums.
Periodontitis—A gum disease that destroys the
structures supporting the teeth, including bone.
Plaque—A thin, sticky, colorless film of bacteria
that forms on teeth.
Tartar—A hardened yellow or brown mineral deposit from unremoved plaque; also called calculus.

Tooth decay, also called dental caries or cavities,
is a common dental problem that results when the acid
produced by plaque bacteria destroys the outer surface of a tooth. A dentist will remove the decay and fill
the cavity with an appropriate dental material to
restore and protect the tooth; left untreated, the
decay will expand, destroying the entire tooth and
causing significant pain.

Normal results
With proper brushing and flossing, oral hygiene
may be maintained and oral health problems may be
avoided. Older adults may no longer assume that they
will lose all of their teeth in their lifetime. Regular oral
care preserves speech and eating functions, thus
prolonging the quality of life.

Inside the eyelid is a septum. The septum divides
the eyelid into outer and inner areas. This orbital
septum helps prevent the spread of infection to the
eye socket. Periorbital and orbital cellulitis are more
common in children than in adults. Periorbital cellulitis, which accounts for 85–90% of all ocular cellulitis,
usually occurs in children under the age of five.
Responsible for the remaining 10–15% of these infections, orbital cellulitis is most common in children
over the age of five.
These conditions usually begin with swelling or
inflammation of one eye. Infection spreads rapidly
and can cause serious problems that affect the eye or
the whole body.

Causes and symptoms
Orbital and periorbital cellulitis are usually
caused by infection of the sinuses near the nose.
Insect bites or injuries that break the skin cause
about one-third of these cellulitis infections. Orbital
and periorbital cellulitis may also occur in people with
a history of dental infections.
The blood of about 33 of every 100 patients with
orbital or periorbital cellulitis contains bacteria
known to cause:

Resources



acute ear infections

ORGANIZATIONS



inflammation of the epiglottis (the cartilage flap that
covers the opening of the windpipe during
swallowing)



meningitis (inflammation of the membranes that
enclose and protect the brain)



pneumonia



sinus infection.

American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.
American Dental Hygienists’ Association. 444 North
Michigan Ave., Chicago, IL 60611. (800) 847-6718.
OTHER

Healthtouch Online Page. <http://www.healthtouch.com>.

Bethany Thivierge

Oral hypoglycemics see Antidiabetic drugs
2696

People with periorbital cellulitis will have swollen,
painful lids and redness, but probably no fever. About
one child in five has a runny nose, and 20% have
conjunctivitis. Conjunctivitis, also called pinkeye, is
an inflammation of the mucous membrane that lines
GALE ENCYCLOPEDIA OF MEDICINE

As well as a swollen lid, other symptoms of orbital
cellulitis include:


bulging or displacement of the eyeball (proptosis)



Chemosis (swelling of the mucous membrane of the
eyeball and eyelid as a result of infection, injury, or
systemic disorders like anemia or kidney disease)

Prognosis
If diagnosed promptly and treated with antibiotics, most orbital and periorbital cellulitis can be
cured. These conditions are serious and need prompt
treatment.
Infections that spread beyond the eye socket can
cause:


abscesses in the brain or in the protective membranes
that enclose it



diminished ability to see clearly



bacterial meningitis



eye pain



blood clots



fever



vision loss



paralysis of nerves that control eye movements
(ophthalmoplegia)

Resources
ORGANIZATIONS

Diagnosis
An eye doctor may use special instruments to
open a swollen lid in order to:


examine the position of the eyeball



evaluate eye movement



test the patient’s vision.

If the source of infection is not apparent, the
position of the eyeball may suggest its location.
Computed tomography scans (CT scans) can indicate
which sinuses and bones are involved or whether
abscesses have developed.

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100.
<http://www.aoanet.org>.

Maureen Haggerty

Orchiectomy see Testicular surgery
Orchiopexy see Testicular surgery

Treatment
A child who has orbital or periorbital cellulitis
should be hospitalized without delay. Antibiotics are
used to stop the spread of infection and prevent
damage to the optic nerve, which transmits visual
images to the brain.
Symptoms of optic-nerve damage or infection
that has spread to sinus cavities close to the brain
include:


very limited ability to move the eye



impaired response of the pupil to light and other
stimulus



loss of visual acuity



papilledema (swelling of the optic disk—where the
optic nerve enters the eye)

One or both eyes may be affected, and eye sockets
or sinus cavities may have to be drained. These surgical procedures should be performed by an ophthalmologist or otolaryngologist.
GALE ENCYCLOPEDIA OF MEDICINE

Orchitis
Definition
Orchitis is an inflammation of the testis, accompanied by swelling, pain, fever, and a sensation of
heaviness in the affected area.

Description
Viral mumps is the most common cause of orchitis. Bacterial infections associated with the disorder
are tuberculosis, syphilis, gonorrhea, and chlamydia.
A mechanical injury to the groin area may also cause
orchitis. Fifteen to twenty-five percent of males past
the age of puberty with mumps develop orchitis.
Epididymo-orchitis (inflammation of both testes and
part of the spermatic duct) is the most common
bacterial type of Orchitis. This form of the condition
occurs most often in sexually active males fifteen years
and older, and in men over 45 with enlarged prostates.
2697

Orchitis

the eyelid and covers the front white part of the eye. It
can be caused by allergy, irritation, or bacterial or
viral infection.

Orthopedic surgery

Causes and symptoms
The people most susceptible to orchitis are those
with inadequate mumps inoculation and, in the case
of sexually transmitted orchitis, those who practice
unsafe sex or have a history of sexually transmitted
disease. Inadequate protection of the groin area
during contact sports or other potentially harmful
physical activities may result in injury leading to orchitis. Symptoms of orchitis include swelling of one or
both testicles, tenderness in the groin area, fever, headache, and nausea. Symptoms may also include bloody
discharge from the penis, and pain during urination,
intercourse, or ejaculation.

Diagnosis
In most cases, Orchitis can be diagnosed by an
urologist, general practitioner, or emergency room
physician. Diagnosis is usually based on the results
of a physical examination and patient history. Other
testing may include a urinalysis and urine culture,
screening for chlamydia and gonorrhea, ultrasound
imaging, or blood tests.

Treatment
Elevation and support of the scrotum, and the
application of cold packs to the groin area give some
relief from the pain of orchitis. Medication for pain
such as codeine and meperidine may be given. Only
the symptoms of viral mumps orchitis are treated.
Antibiotics are used to alleviate orchitis that is bacterial in origin. Sexually transmitted orchitis (especially
when resultant from chlamydia or gonorrhea) is often
treated with the antibiotic Ceftriaxone in conjunction
with azithromycin or doxycycline.

Alternative treatment
For relief from swelling, the drinking of dandelion
tea is recommended in traditional Chinese medicine
(TCM). Another traditional Chinese treatment for
swelling is the application of a poultice of ground dandelion and aloe to the affected area. Homeopathic
remedies to reduce swelling include apis mel, belladonna, and pulsatilla. Consult a homeopathic physician before taking or administering these remedies to
ensure safe and correct dosage.

KEY TERMS
Atrophy—A wasting away or withering.
Epididymo-orchitis—Inflammation of both the
testes and a part of the spermatic duct system.
Unilateral—Affecting only one side.

Prevention
Keeping mumps inoculations current and diligently practicing safe sex are the best ways to prevent
orchitis from occurring. For males involved in contact
sports or other potentially harmful physical activities,
the wearing of a protective cup over the genitals will
help guard against mechanical injuries that could lead
to orchitis.
Resources
PERIODICALS

Rodriguez, Rod. ‘‘Acute Scrotum Due to EpididymoOrchitis in Male Children.’’ Impotence & Male Health
Weekly Plus February 1999.
OTHER

Mycyck, Mark, MD. ‘‘Orchitis from Emergency Medicine/
Genitourinary.’’ Emedicine, Instant Access to the Minds
of Medicine. February 2001. <http://www.emedicine.
com/emerg/topic344.htm>.

Mary Jane Tenerelli, MS

Organophosphates see Insecticide poisoning
Oriental sore see Leishmaniasis
Ornithosis see Parrot fever
Oroya fever see Bartonellosis

Orthopedic surgery
Definition

Prognosis
Orchitis is usually unilateral and lasts between one
and two weeks. Atrophy of the scrotum occurs in 60%
of orchitis cases. However, hormonal function is not
affected and resulting sterility is rare from mumps.
2698

Orthopedic (sometimes spelled orthopaedic) surgery is surgery performed by a medical specialist, such
as an orthopedist or orthopedic surgeon, trained to
deal with problems that develop in the bones, joints,
and ligaments of the human body.
GALE ENCYCLOPEDIA OF MEDICINE

Orthopedic surgery corrects problems that arise in
the skeleton and its attachments, the ligaments and
tendons. It may also deal with some problems of the
nervous system, such as those that arise from injury of
the spine. These problems can occur at birth, through
injury, or as the result of aging. They may be acute, as
in injury, or chronic, as in many aging-related
problems.
Orthopedics comes from two Greek words, ortho,
meaning straight and pais, meaning child. Originally
orthopedic surgeons dealt with bone deformities in
children, using braces to straighten the child’s bones.
With the development of anesthesia and an understanding of the importance of aseptic technique in
surgery, orthopedic surgeons extended their role to
include surgery involving the bones and related nerves
and connective tissue.
The terms orthopedic surgeon and orthopedist are
used interchangeably today to indicate a medical doctor with special certification in orthopedics.
Many orthopedic surgeons maintain a general
practice, while some specialize in one particular aspect
of orthopedics, such as hand surgery, joint replacements, or disorders of the spine. Orthopedics treats
both acute and chronic disorders. Some orthopedists
specialize in trauma medicine and can be found in
emergency rooms and trauma centers treating injuries.
Others find their work overlapping with plastic surgeons, geriatric specialists, pediatricians, or podiatrists
(foot care specialists). A rapidly growing area of orthopedics is sports medicine, and many sports medicine
doctors are board certified orthopedists.

Precautions
Choosing an orthopedist is an important step in
obtaining appropriate treatment. Patients looking for
a qualified orthopedist should inquire if they are
‘‘board certified’’ by their accrediting organization.

In general orthopedists are attached to a hospital,
medical center, trauma center, or free-standing surgical center where they work closely with a surgical team
including an anesthesiologist and surgical nurse.
Orthopedic surgery can be performed under general,
regional, or local anesthesia.
Much of the work of the surgeon involves adding
foreign material to the body in the form of screws,
wires, pins, tongs, and prosthetics to hold damaged
bones in their proper alignment or to replace damaged
bone or connective tissue. Great improvements have
been made in the development of artificial limbs and
joints, and in the materials available to repair damage
to bones and connective tissue. As developments occur
in the fields of metallurgy and plastics, changes will take
place in orthopedic surgery that will allow the surgeon
to more nearly duplicate the natural functions of the
bones, joints, and ligaments, and to more accurately
restore damaged parts to their original range of motion.

Preparation
Patients are usually referred to an orthopedic surgeon by a general physical or family doctor. Prior to
any surgery, the patient undergoes extensive testing to
determine the proper corrective procedure. Tests may
include x rays, computed tomography scans (CT scans),
magnetic resonance imaging (MRI), myelograms, diagnostic arthroplasty, and blood tests. The orthopedist
will determine the history of the disorder and any
treatments that were tried previously. A period of
rest to the injured part may be recommended before
surgery is prescribed.
Patients undergo standard blood and urine tests
before surgery and, for major surgery, may be given an
electrocardiogram or other diagnostic tests prior to
the operation. Patients may choose to give some of
their own blood to be held in reserve for their use in
major surgery, such as knee replacement, where heavy
bleeding is common.

Aftercare
Description
The range of treatments done by orthopedists is
enormous. It can cover anything from traction to
amputation, hand reconstruction to spinal fusion or
joint replacements. They also treat broken bones,
strains and sprains, and dislocations. Some specific
procedures done by orthopedic surgeons are listed as
separate entries in this book, including arthroplasty,
arthroscopic surgery, bone grafting, fasciotomy, fracture
repair, kneecap removal, and traction.
GALE ENCYCLOPEDIA OF MEDICINE

Rehabilitation from orthopedic injuries can be a
long, arduous task. The doctor will work closely with
physical therapists to assure that the patient is receiving treatment that will enhance the range of motion
and return function to the affected part.

Risks
As with any surgery, there is always the risk of
excessive bleeding, infection, and allergic reaction to
2699

Orthopedic surgery

Purpose

Orthostatic hypotension

Description

KEY TERMS
Arthroplasty—The surgical reconstruction or
replacement of a joint.
Prosthesis—A synthetic replacement for a missing
part of the body, such as a knee or a hip.
Range of motion—The normal extent of movement
(flexion and extension) of a joint.

anesthesia. Risks specifically associated with orthopedic surgery include inflammation at the site where
foreign material (pins, prosthesis) is introduced into
the body, infection as the result of surgery, and
damage to nerves or to the spinal cord.

Normal results
Thousands of people have successful orthopedic
surgery each year to recover from injuries or restore
lost function. The degree of success in individual
recoveries depends on the age and general health of
the patient, the medical problem being treated, and the
patient’s willingness to comply with rehabilitative
therapy after the surgery.
Resources
ORGANIZATIONS

American Academy of Orthopaedic Surgeons. 6300 North
River Road, Rosemont, IL 60018-4262. (800) 823-8125.
<http://www.AAOS.org>.
American Osteopathic Board of Orthopedic Surgery.
<http://www.netincom.com/aobos/about.html>.
OTHER

Orthogate. <http://owl.orthogate.org/>.

When a person stands upright, a certain amount
of blood normally pools in the veins of the ankles and
legs. This pooling means that there is slightly less
blood for the heart to pump and causes a drop in
blood pressure. Usually, the body responds to this
drop so quickly, a person is unaware of the change.
The brain tells the blood vessels to constrict so they
have less capacity to carry blood, and at the same time
tells the heart to beat faster and harder. These
responses last for a very brief time. If the body’s
response to a change in vertical position is slow or
absent, the result is orthostatic hypotension. It is not
a true disease, but the inability to regulate blood pressure quickly.

Causes and symptoms
Orthostatic hypotension has many possible
causes. The most common cause is medications used
to treat other conditions. Diuretics reduce the amount
of fluid in the body which reduces the volume of
blood. Medicines used to expand the blood vessels
increase the vessel’s ability to carry blood and so
lower blood pressure.
If there is a severe loss of body fluid from vomiting, diarrhea, untreated diabetes, or even excessive
sweating, blood volume will be reduced enough to
lower blood pressure. Severe bleeding can also result
in orthostatic hypotension.
Any disease or spinal cord injury that damages the
nerves which control blood vessel diameter can cause
orthostatic hypotension.
Symptoms of orthostatic hypotension include
faintness, dizziness, confusion, or blurry vision, when
standing up quickly. An excessive loss of blood pressure can cause a person to pass out.

Tish Davidson, A.M.

Diagnosis

Orthopedic x rays see Bone x rays

Orthostatic hypotension
Definition
Orthostatic hypotension is an abnormal decrease
in blood pressure when a person stands up. This may
lead to fainting.
2700

When a person experiences any of the symptoms
above, a physician can confirm orthostatic hypotension if the person’s blood pressure falls significantly on
standing up and returns to normal when lying down.
The physician will then look for the cause of the
condition.

Treatment
When the cause of orthostatic hypotension is
related to medication, it is often possible to treat
it by reducing dosage or changing the prescription.
GALE ENCYCLOPEDIA OF MEDICINE

Medications designed to keep blood pressure
from falling can be used when they will not interfere
with other medical problems.
When orthostatic hypotension cannot be treated,
the symptoms can be significantly reduced by remembering to stand up slowly or by wearing elastic
stockings.

Prognosis
The prognosis for people who have orthostatic
hypotension depends on the underlying cause of the
problem.

Prevention
There is no way to prevent orthostatic hypotension, since it is usually the result of another medical
condition.

name osteoarthritis comes from three Greek words
meaning bone, joint, and inflammation.

Description
OA is one of the most common causes of disability
due to limitations of joint movement, particularly in
people over 50. It is estimated that 2% of the United
States population under the age of 45 suffers from
osteoarthritis; this figure rises to 30% of persons
between 45 and 64, and 63–85% in those over 65.
About 90% of the American population will have
some features of OA in their weight-bearing joints by
age 40. Men tend to develop OA at earlier ages than
women.
OA occurs most commonly after 40 years of age
and typically develops gradually over a period of
years. Patients with OA may have joint pain on only
one side of the body and it primarily affects the knees,
hands, hips, feet, and spine.

Causes and symptoms

Resources
ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Dorothy Elinor Stonely

Orthotopic transplantation see Liver
transplantation
Osgood-Schlatter disease see
Osteochondroses
Osteitis deformans see Paget’s disease of
bone

Osteoarthritis
Definition
Osteoarthritis (OA), which is also known as
osteoarthrosis or degenerative joint disease (DJD), is
a progressive disorder of the joints caused by gradual
loss of cartilage and resulting in the development of
bony spurs and cysts at the margins of the joints. The
GALE ENCYCLOPEDIA OF MEDICINE

Osteoarthritis results from deterioration or loss of
the cartilage that acts as a protective cushion between
bones, particularly in weight-bearing joints such as the
knees and hips. As the cartilage is worn away, the bone
forms spurs, areas of abnormal hardening, and fluidfilled pockets in the marrow known as subchondral
cysts. As the disorder progresses, pain results from
deformation of the bones and fluid accumulation in
the joints. The pain is relieved by rest and made worse
by moving the joint or placing weight on it. In early
OA, the pain is minor and may take the form of mild
stiffness in the morning. In the later stages of OA,
inflammation develops; the patient may experience
pain even when the joint is not being used; and he or
she may suffer permanent loss of the normal range of
motion in that joint.
Until the late 1980s, OA was regarded as an inevitable part of aging, caused by simple ‘‘wear and tear’’
on the joints. This view has been replaced by recent
research into cartilage formation. OA is now considered to be the end result of several different factors
contributing to cartilage damage, and is classified as
either primary or secondary.
Primary osteoarthritis
Primary OA results from abnormal stresses on
weight-bearing joints or normal stresses operating on
weakened joints. Primary OA most frequently affects
the finger joints, the hips and knees, the cervical and
lumbar spine, and the big toe. The enlargements of the
2701

Osteoarthritis

If it is caused by low blood volume, an increase in fluid
intake and retention will solve the problem.

Osteoarthritis

finger joints that occur in OA are referred to as
Heberden’s and Bouchard’s nodes. Some gene mutations appear to be associated with OA. Obesity also
increases the pressure on the weight-bearing joints of
the body. Finally, as the body ages, there is a reduction
in the ability of cartilage to repair itself. In addition to
these factors, some researchers have theorized that
primary OA may be triggered by enzyme disturbances,
bone disease, or liver dysfunction.
Secondary osteoarthritis
Secondary OA results from chronic or sudden
injury to a joint. It can occur in any joint. Secondary
OA is associated with the following factors:


trauma, including sports injuries



repetitive stress injuries associated with certain occupations (like the performing arts, construction or assembly line work, computer keyboard operation, etc.)



repeated episodes of gout or septic arthritis



poor posture or bone alignment caused by developmental abnormalities



metabolic disorders

Diagnosis
History and physical examination
The two most important diagnostic clues in the
patient’s history are the pattern of joint involvement
and the presence or absence of fever, rash, or other
symptoms outside the joints. As part of the physical
examination, the doctor will touch and move the patient’s
joint to evaluate swelling, limitations on the range
of motion, pain on movement, and crepitus (a cracking
or grinding sound heard during joint movement).
Diagnostic imaging
There is no laboratory test that is specific for
osteoarthritis. Treatment is usually based on the
results of diagnostic imaging. In patients with OA,
x-rays may indicate narrowed joint spaces, abnormal
density of the bone, and the presence of subchondral
cysts or bone spurs. The patient’s symptoms, however,
do not always correlate with x-ray findings. Magnetic
resonance imaging (MRI) and computed tomography
scans (CT scans) can be used to determine more
precisely the location and extent of cartilage damage.

of the joints involved, the rate of progression, the
severity of symptoms, the degree of disability, and
responses to specific forms of treatment. Most treatment programs include several forms of therapy.
Patient education and psychotherapy
Patient education is an important part of OA
treatment because of the highly individual nature of
the disorder and its potential impacts on the patient’s
life. Patients who are depressed because of changes in
employment or recreation usually benefit from counseling. The patient’s family should be involved in discussions of coping, household reorganization, and
other aspects of the patient’s disease and treatment
regimen.
Medications
Patients with mild OA may be treated only with
pain relievers such as acetaminophen (Tylenol). Most
patients with OA, however, are given nonsteroidal
anti-inflammatory drugs, or NSAIDs. These include
compounds such as ibuprofen (Motrin, Advil), ketoprofen (Orudis), and flurbiprofen (Ansaid). The
NSAIDs have the advantage of relieving inflammation as well as pain. They also have potentially dangerous side effects, including stomach ulcers,
sensitivity to sun exposure, kidney disturbances, and
nervousness or depression.
Some OA patients are treated with corticosteroids
injected directly into the joints to reduce inflammation
and slow the development of Heberden’s nodes.
Injections should not be regarded as a first-choice
treatment and should be given only two or three
times a year.
Most recently, a new class of NSAIDs, known as
the cyclo-oxygenase-2 (COX-2) inhibitors have been
studied and approved for the treatment of OA. These
COX-2 inhibitors work to block the enzyme COX-2,
which stimulates inflammatory responses in the body.
They work to decrease both the inflammation and joint
pain of OA, but without the high risk of gastrointestinal
ulcers and bleeding seen with the traditional NSAIDs.
This is due to the fact that they do not block COX-1,
which is another enzyme that has protective effects on
the stomach lining. The COX-2 inhibitors included
celecoxib (Celebrex) and rofecoxib (Vioxx). Celecoxib
is taken once or twice daily, and rofecoxib once daily.
Physical therapy

Treatment
Treatment of OA patients is tailored to the needs
of each individual. Patients vary widely in the location
2702

Patients with OA are encouraged to exercise as a
way of keeping joint cartilage lubricated. Exercises
that increase balance, flexibility, and range of motion
GALE ENCYCLOPEDIA OF MEDICINE

Osteoarthritis

Periosteum
Cartilage
coating the
bone ends

Articulating
bone
Synovial (joint)
cavity (contains
synovial fluid)

Degeneration
of cartilage

Articular
capsule
Periosteum
Synovial
membrane
Articulating
bone
(A)

(B)
Normal joint

Early stage of
osteoarthritis

Bone
outgrowth

Thickened
bone

Fused joint

Cartilage
particles
Loss of
cartilage
(C)

(D)

Late stage of disease

The progression of osteoarthritis. (Illustration by Hans & Cassady.)

are recommended for OA patients. These may include
walking, swimming and other water exercises, yoga
and other stretching exercises, or isometric exercises.
Physical therapy may also include massage, moist
hot packs, or soaking in a hot tub.

collars, crutches, canes, hip braces, knee supports, bed
boards, or elevated chair and toilet seats. They are also
advised to avoid unnecessary knee bending, stair
climbing, or lifting of heavy objects.
New treatments

Surgery
Surgical treatment of osteoarthritis may include
the replacement of a damaged joint with an artificial
part or appliance; surgical fusion of spinal bones; scraping or removal of damaged bone from the joint; or the
removal of a piece of bone in order to realign the bone.
Protective measures
Depending on the location of the affected joint,
patients with OA may be advised to use neck braces or
GALE ENCYCLOPEDIA OF MEDICINE

Since 1997, several new methods of treatment for
OA have been investigated. Although they are still
being developed and tested, they appear to hold promise. They include:


Disease-modifying drugs. These compounds may be
useful in assisting the body to form new cartilage or
improve its repair of existing cartilage.



Hyaluronic acid. Injections of this substance may
help to lubricate and protect cartilage, thereby promoting flexibility and reduced pain. These agents
2703

Osteoarthritis

include hyaluronan (Hyalgan) and hylan G-F20
(Synvisc).


KEY TERMS

Cartilage transplantation. This technique is presently
used in Sweden.

Bouchard’s nodes—Swelling of the middle joint of
the finger.
Cartilage—Elastic connective tissue that covers
and protects the ends of bones.

Alternative treatment
Diet

Heberden’s nodes—Swelling or deformation of the
finger joints closest to the fingertips.
Primary osteoarthritis—OA that results from hereditary factors or stresses on weight-bearing joints.

Food intolerance can be a contributing factor in
OA, although this is more significant in rheumatoid
arthritis. Dietary suggestions that may be helpful
for people with OA include emphasizing high-fiber,
complex-carbohydrate foods, while minimizing fats.
Plants in the Solanaceae family, such as tomatoes,
eggplant, and potatoes, should be avoided, as should
refined and processed foods. Foods that are high
in bioflavonoids (berries as well as red, orange, and
purple fruits and vegetables) should be eaten often.

Secondary osteoarthritis—OA that develops following joint surgery, trauma,or repetitive joint injury.
Subchondral cysts—Fluid-filled sacs that form
inside the marrow at the ends of bones as part of
the development of OA.

Nutritional supplements
In the past several years, a combination of glucosamine and chondroitin sulfate has been proposed as a
dietary supplement that helps the body maintain and
repair cartilage. Studies conducted in Europe have
shown the effectiveness of this treatment in many
cases. These substances are nontoxic and do not require
prescriptions. Other supplements that may be helpful in
the treatment of OA include the antioxidant vitamins
and minerals (vitamins A, C, E, selenium, and zinc) and
the B vitamins, especially vitamins B6 and B5.
Naturopathy
Naturopathic treatment for OA includes hydrotherapy, diathermy (deep-heat therapy), nutritional
supplements, and botanical preparations, including
yucca, devil’s claw (Harpagophytum procumbens),
and hawthorn (Crataegus laevigata) berries.
Traditional Chinese medicine (TCM)
Practitioners of Chinese medicine treat arthritis
with suction cups, massage, moxibustion (warming an
area of skin by burning a herbal wick a slight distance
above the skin), the application of herbal poultices, and
internal doses of Chinese herbal formulas.
Other alternatives
Recently, several alternative treatments for OA
have received considerable attention and study. These
include:


transcutaneous electrical nerve stimulation (TENS)



magnet therapy

2704



therapeutic touch



acupuncture



yoga

Prognosis
OA is a progressive disorder without a permanent
cure. In some patients, the rate of progression can be
slowed by weight loss, appropriate exercise, surgical
treatment, and the use of alternative therapies.
Resources
PERIODICALS

Berger, R. G. ‘‘Intelligent Use of NSAIDs: Where Do We
Stand.’’Expert Opinions in Pharmacotherapy 1, no. 2
(January 2001): 19-30.
Brandt, K. D. ‘‘The Role of Analgesics in the Management
of Osteoarthritis.’’ American Journal of Therapeutics
March 2000: 75-90.
Little, C. V., and T. Parsons. ‘‘Herbal Therapy for Treating
Osteoarthritis.’’ Cochrane Database System Review
2001: 1.
Pavelka, K. ‘‘Treatment of Pain in Osteoarthritis.’’European
Journal of Pain 2000: 23-30.
Schnitzer, T. J. ‘‘Osteoarthritis Management: The Role of
Cyclooxygenase-2-selective Inhibitors.’’ Clinical
Therapeutics March 2001: 313-26.
Towheed, T. E., et al. ‘‘Glucosamine Therapy for Treating
Osteoarthritis.’’ Cochrane Database System Review
2001: 1.

Liz Meszaros

Osteoarthrosis see Osteoarthritis
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Osteochondroses is a group of diseases of children
and adolescents in which localized tissue death (necrosis)
occurs, usually followed by full regeneration of healthy
bone tissue. The singular term is osteochondrosis.

Scheuermann’s disease can lead to serious kyphosis (hunchback condition) due to erosion of the
vertebral bodies. Usually, however, the kyphosis is
mild, causing no further symptoms and requiring no
special treatment.

Diagnosis
Description
During the years of rapid bone growth, blood
supply to the growing ends of bones (epiphyses) may
become insufficient resulting in necrotic bone, usually
near joints. The term avascular necrosis is used to
describe osteochondrosis. Since bone is normally
undergoing a continuous rebuilding process, the necrotic areas are most often self-repaired over a period of
weeks or months.
Osteochondrosis can affect different areas of the
body and is often categorized by one of three locations: articular, non-articular, and physeal.
Physeal osteochondrosis is known as Scheuermann’s
disease. It occurs in the spine at the intervertebral joints
(physes), especially in the chest (thoracic) region.
Articular disease occurs at the joints (articulations).
One of the more common forms is Legg-Calvé-Perthes
disease, occurring at the hip. Other forms include
Köhler’s disease (foot), Freiberg’s disease (second toe),
and Panner’s disease (elbow). Freiberg’s disease is the
one type of osteochondrosis that is more common in
females than in males. All others affect the sexes equally.
Non-articular osteochondrosis occurs at any other
skeletal location. For instance, Osgood-Schlatter disease of the tibia (the large inner bone of the leg between
the knee and ankle) is relatively common.
Osteochondritis dissecans is a form of osteochondrosis in which loose bone fragments may form in a
joint.

Diagnosis can be confirmed by x-ray findings.

Treatment
Conservative treatment is usually attempted first.
In many cases, simply resting the affected body part
for a period of days or weeks will bring relief. A cast
may be applied if needed to prevent movement of a joint.
Surgical intervention may be needed in some
cases of osteochondritis dissecans to remove abnormal
bone fragments in a joint.

Prognosis
Accurate prediction of the outcome for individual
patients is difficult with osteochondrosis. Some patients
will heal spontaneously. Others will heal with little
treatment other than keeping weight or stress off the
affected limb. The earlier the age of onset, the better
the prospects for full recovery. Surgical intervention
is often successful in osteochondritis dissecans.

Prevention
No preventive measures are known.
Resources
BOOKS

Eilert, Robert E., and Gaia Geogopoulos. ‘‘Orthopedics.’’
In Current Pediatric Diagnosis and Treatment, edited by
W. W. Hay, Jr., et al. Stamford: Appleton & Lange, 1997.

Victor Leipzig, PhD

Causes and symptoms
Many theories have been advanced to account
for osteochondrosis, but none has proven fully satisfactory. Stress and ischemia (reduced blood supply)
are two of the most commonly mentioned factors.
Athletic young children are often affected when they
overstress their developing limbs with a particular
repetitive motion. Many cases are idiopathic, meaning
that no specific cause is known.
The most common symptom for most types of
osteochondrosis is simply pain at the affected joint,
GALE ENCYCLOPEDIA OF MEDICINE

Osteogenesis imperfecta
Definition
Osteogenesis imperfecta (OI) is a group of genetic
diseases of collagen in which the bones are formed
improperly, making them fragile and prone to breaking.
2705

Osteogenesis imperfecta

Osteochondroses

especially when pressure is applied. Locking of a joint
or limited range of motion at a joint can also occur.

Osteogenesis imperfecta

Description
Collagen is a fibrous protein material. It serves as
the structural foundation of skin, bone, cartilage, and
ligaments. In osteogenesis imperfecta, the collagen
produced is abnormal and disorganized. This results
in a number of abnormalities throughout the body, the
most notable being fragile, easily broken bones.
There are four forms of OI, Types I through IV.
Of these, Type II is the most severe, and is usually fatal
within a short time after birth. Types I, III, and IV
have some overlapping and some distinctive symptoms, particularly weak bones.
Evidence suggests that OI results from abnormalities in the collagen gene COL1A1 or COL1A2, and
possibly abnormalities in other genes. In OI Type I,
II, and III, the gene map locus is 17q21.31-q22,
7q22.1, and in OI Type IV, the gene map locus is
17q21.31-q22.
In OI, the genetic abnormality causes one of two
things to occur. It may direct cells to make an altered
collagen protein and the presence of this altered collagen causes OI Type II, III, or IV. Alternately, the
dominant altered gene may fail to direct cells to make
any collagen protein. Although some collagen is produced by instructions from the normal gene, an overall
decrease in the total amount of collagen produced
results in OI Type I.
A child with only one parent who is a carrier of a
single altered copy of the gene has no chance of actually having the disease, but a 50% chance of being a
carrier.
If both parents have OI caused by an autosomal
dominant gene change, there is a 75% chance that the
child will inherit one or both OI genes. In other words,
there is a 25% chance the child will inherit only the
mother’s OI gene (and the father’s unaffected gene), a
25% chance the child will inherit only the father’s OI
gene (and the mother’s unaffected gene), and a 25%
chance the child will inherit both parents’ OI genes.
Because this situation has been uncommon, the outcome of a child inheriting two OI genes is hard to
predict. It is likely that the child would have a severe,
possibly lethal, form of the disorder.
About 25% of children with OI are born into a
family with no history of the disorder. This occurs
when the gene spontaneously mutates in either the
sperm or the egg before the child’s conception. No
triggers for this type of mutation are known. This is
called a new dominant mutation. The child has a 50%
chance of passing the disorder on to his or her children. In most cases, when a family with no history of
2706

OI has a child with OI, they are not at greater risk than
the general population for having a second child with
OI, and unaffected siblings of a person with OI are at
no greater risk of having children with OI than the
general population.
In studies of families into which infants with OI
Type II were born, most of the babies had a new
dominant mutation in a collagen gene. In some of
these families, however, more than one infant was
born with OI. Previously, researchers had seen this
recurrence as evidence of recessive inheritance of this
form of OI. More recently, however, researchers have
concluded that the rare recurrence of OI to a couple
with a child with autosomal dominant OI is more
likely due to gonadal mosaicism. Instead of mutation
occurring in an individual sperm or egg, it occurs in a
percentage of the cells that give rise to a parent’s
multiple sperm or eggs. This mutation, present in a
percentage of his or her reproductive cells, can result in
more than one affected child without affecting the
parent with the disorder. An estimated 2%–4% of
families into which an infant with OI Type II is born
are at risk of having another affected child because of
gonadal mosaicism.

Demographics
OI affects equal numbers of males and females. It
occurs in about one of every 20,000 births.

Causes and symptoms
OI is usually inherited as an autosomal dominant
condition. In autosomal dominant inheritance, a single abnormal gene on one of the autosomal chromosomes (one of the first 22 ‘‘non-sex’’ chromosomes)
from either parent can cause the disease. One of the
parents will have the disease (since it is dominant) and
is the carrier. Only one parent needs to be a carrier in
order for the child to inherit the disease. A child who
has one parent with the disease has a 50% chance of
also having the disease.
Type I
This is the most common and mildest type.
Among the common features of Type I are the
following:


bones are predisposed to fracture, with most fractures occurring before puberty; people with OI type I
typically have about 20–40 fractures before puberty.



stature is normal or near-normal



joints are loose and muscle tone is low
GALE ENCYCLOPEDIA OF MEDICINE

usually sclera (whites of the eyes) have blue, purple,
or gray tint



face shape is triangular



tendency toward scoliosis (a curvature of the spine)



bone deformity is absent or minimal



dentinogenesis imperfecta may occur, causing brittle
teeth



hearing loss is a possible symptom, often beginning
in early 20s or 30s



structure of collagen is normal, but the amount is less
than normal
Type II

Sometimes called the lethal form, Type II is the
most severe form of OI. Among the common features
of Type II are the following:


frequently, OI Type II is lethal at or shortly after
birth, often as a result of respiratory problems



fractures are numerous and bone deformity is severe



stature is small with underdeveloped lungs



collagen is formed improperly
Type III

Among the common features of Type III are the
following:


bones fracture easily (fractures are often present at
birth, and x rays may reveal healed fractures that
occurred before birth; people with OI Type III may
have more than 100 fractures before puberty)



stature is significantly shorter than normal



sclera (whites of the eyes) have blue, purple, or gray
tint



joints are loose and muscle development is poor in
arms and legs



rib cage is barrel-shaped



face shape is triangular



scoliosis (a curvature of the spine) is present



respiratory problems are possible



bones are deformed and deformity is often severe



dentinogenesis imperfecta may occur, causing brittle
teeth



hearing loss is possible



collagen is formed improperly

GALE ENCYCLOPEDIA OF MEDICINE

Type IV
OI Type IV falls between Type I and Type III in
severity. Among the common features of Type IV are
the following:


bones fracture easily, with most fractures occurring
before puberty



stature is shorter than average



sclera (whites of the eyes) are normal in color,
appearing white or near-white



bone deformity is mild to moderate



scoliosis (curvature of the spine) is likely



rib cage is barrel-shaped



face is triangular in shape



dentinogenesis imperfecta may occur, causing brittle
teeth



hearing loss is possible



collagen is formed improperly

Diagnosis
It is often possible to diagnose OI solely on clinical
features and x-ray findings. Collagen or DNA tests
may help confirm a diagnosis of OI. These tests generally require several weeks before results are known.
Approximately 10–15% of individuals with mild OI
who have collagen testing, and approximately 5% of
those who have genetic testing, test negative for OI
despite having the disorder.
Diagnosis is usually suspected when a baby has
bone fractures after having suffered no apparent
injury. Another indication is small, irregular, isolated
bones in the sutures between the bones of the skull
(wormian bones). Sometimes the bluish sclera serves
as a diagnostic clue. Unfortunately, because of the
unusual nature of the fractures occurring in a baby
who cannot yet move, some parents have been accused
of child abuse before the actual diagnosis of osteogenesis imperfecta was reached.
Prenatal diagnosis
Testing is available to assist in prenatal diagnosis.
Women with OI who become pregnant, or women
who conceive a child with a man who has OI, may
wish to explore prenatal diagnosis. Because of the
relatively small risk (2–4%) of recurrence of OI Type
II in a family, families may opt for ultrasound studies
to determine if a developing fetus has the disorder.
Ultrasound is the least invasive procedure for
prenatal diagnosis, and carries the least risk. Using
2707

Osteogenesis imperfecta



Osteogenesis imperfecta

ultrasound, a doctor can examine the fetus’s skeleton
for bowing of the leg or arm bones, fractures, shortening, or other bone abnormalities that may indicate
OI. Different forms of OI may be detected by ultrasound in the second trimester. The reality is that when
it occurs as a new dominant mutation, it is found
inadvertantly on ultrasound, and it may be difficult
to know the diagnosis until after delivery since other
genetic conditions can cause bowing and/or fractures
prenatally.
Chorionic villus sampling is a procedure to obtain
chorionic villi tissue for testing. Examination of fetal
collagen proteins in the tissue can reveal information
about the quantitative or qualitative collagen defects
that leads to OI. When a parent has OI, it is necessary
for the affected parent to have the results of his or her
own collagen test available. Chorionic villus sampling
can be performed at 10–12 weeks of pregnancy.
Amniocentesis is a procedure that involves inserting a thin needle into the uterus, into the amniotic sac,
and withdrawing a small amount of amniotic fluid.
DNA can be extracted from the fetal cells contained
in the amniotic fluid and tested for the specific mutation
known to cause OI in that family. This technique is
useful only when the mutation causing OI in a particular family has been identified through previous genetic
testing of affected family members, including previous
pregnancies involving a baby with OI. Amniocentesis
is performed at 16–18 weeks of pregnancy.

Treatment
There are no treatments available to cure OI, nor
to prevent most of its complications. Most treatments
are aimed at treating the fractures and bone deformities caused by OI. Splints, casts, braces, and rods are
all used. Rodding refers to a surgical procedure in
which a metal rod is implanted within a bone (usually
the long bones of the thigh and leg). This is done when
bowing or repeated fractures of these bones has interfered with a child’s ability to begin to walk.
Other treatments include hearing aids and early
capping of teeth. Patients may require the use of
a walker or wheelchair. Pain may be treated with a
variety of medications. Exercise is encouraged as a
means to promote muscle and bone strength.
Swimming is a form of exercise that puts a minimal
amount of strain on muscles, joints, and bones.
Walking is encouraged for those who are able.
Smoking, excessive alcohol and caffeine consumption, and steroid medications may deplete bone and
exacerbate bone fragility.
2708

KEY TERMS
Collagen—The main supportive protein of cartilage, connective tissue, tendon, skin, and bone.
Ligament—A type of connective tissue that connects bones or cartilage and provides support and
strength to joints.
Mutation—A permanent change in the genetic
material that may alter a trait or characteristic of
an individual, or manifest as disease, and can be
transmitted to offspring.
Sclera—The tough white membrane that forms the
outer layer of the eyeball.
Scoliosis—An abnormal, side-to-side curvature of
the spine.

Alternative treatment such as acupuncture, naturopathic therapies, hypnosis, relaxation training,
visual imagery, and biofeedback have all been used to
try to decrease the constant pain of fractures.

Prognosis
Lifespan for people with OI Type I, III, and IV is
not generally shortened. The prognosis for people with
these types of OI is quite variable, depending on the
severity of the disorder and the number and severity of
the fractures and bony deformities.
Fifty percent of all babies with OI Type II are
stillborn. The rest of these babies usually die within a
very short time after birth. In recent years, some people with Type II have lived into young adulthood.
Resources
PERIODICALS

Kocher, M. S., and J. R. Kasser. ‘‘Orthopaedic aspects of
child abuse.’’ Journal of the American Academy of
Orthopedic Surgery 8 (January-February 2000): 10+.
Niyibizi, C., et al. ‘‘Potential of gene therapy for treating
osteogenesis imperfecta.’’ Clinical Orthopedics 379
(October 2000): S126+.
Smith, R. ‘‘Severe osteogenesis imperfecta: new therapeutic
options?’’ British Medical Journal 322 (January 13,
2001): 63+.
Wacaster, Priscilla. ‘‘Osteogenesis Imperfecta.’’Exceptional
Parent 30 (April 2000): 94+.
ORGANIZATIONS

Children’s Brittle Bone Foundation. 7701 95th St., Pleasant
Prairie, WI 53158. (847) 433-498. <http://
www.cbbf.org>.
GALE ENCYCLOPEDIA OF MEDICINE

particularly the thigh bone (femur), one of the
bones of the lower leg (tibia), or the bone of the
upper arm (humerus). This is because in children
these bones have particularly extensive blood circulation, making them more susceptible to invasion by
bacteria. Different patterns of blood circulation in
adults make the long bones less well-served by the
circulatory system. These bones are therefore unlikely to develop osteomyelitis in adult patients.
Instead, the bones of the spine (vertebrae) receive a
lot of blood flow. Therefore, osteomyelitis in adults
is most likely to affect a vertebra. Drug addicts may
have osteomyelitis in the pubic bone or clavicle.

‘‘Osteogenesis Imperfecta.’’ National Institutes of Health
Osteoporosis and Related Bone Diseases–National
Resource Center. <http://www.osteo.org/oi.html>.

Jennifer F. Wilson, MS

Osteogenic sarcoma see Sarcomas
Osteomalacia see Vitamin D deficiency

Osteomyelitis
Definition
Osteomyelitis refers to a bone infection, almost
always caused by a bacteria. Over time, the result can
be destruction of the bone itself.

Description
Bone infections may occur at any age. Certain
conditions increase the risk of developing such an
infection, including sickle cell anemia, injury, the presence of a foreign body (such as a bullet or a screw
placed to hold together a broken bone), intravenous
drug use (such as heroin), diabetes, kidney dialysis,
surgical procedures to bony areas, untreated infections of tissue near a bone (for example, extreme
cases of untreated sinus infections have led to osteomyelitis of the bones of the skull).

Causes and symptoms
Staphylococcus aureus, a bacterium, is the most
common organism involved in osteomyelitis. Other
types of organisms include the mycobacterium which
causes tuberculosis, a type of Salmonella bacteria in
patients with sickle cell anemia, Pseudomonas aeurginosa in drug addicts, and organisms which usually
reside in the gastrointestinal tract in the elderly.
Extremely rarely, the viruses which cause chickenpox
and smallpox have been found to cause a viral
osteomyelitis.
There are two main ways that infecting bacteria
find their way to bone, resulting in the development of
osteomyelitis. These include:


Spread via the bloodstream; 95% of these types of
infections are due to Staphylococcus aureus. In this
situation, the bacteria travels through the bloodstream to reach the bone. In children, the most likely
site of infection is within one of the long bones,

GALE ENCYCLOPEDIA OF MEDICINE



Spread from adjacent infected soft tissue; about 50%
of all such cases are infected by Staphylococcus aureus. This often occurs in cases where recent surgery or
injury has result in a soft tissue infection. The bacteria
can then spread to nearby bone, resulting in osteomyelitis. Patients with diabetes are particularly susceptible to this source of osteomyelitis. The diabetes
interferes with both nerve sensation and good blood
flow to the feet. Diabetic patients are therefore prone
to developing poorly healing wounds to their feet,
which can then spread to bone, causing osteomyelitis.

Acute osteomyelitis refers to an infection which
develops and peaks over a relatively short period of
time. In children, acute osteomyelitis usually presents
itself as pain in the affected bone, tenderness to pressure over the infected area, fever and chills. Patients
who develop osteomyelitis, due to spread from a
nearby area of soft tissue infection, may only note
poor healing of the original wound or infection.
Adult patients with osteomyelitis of the spine
usually have a longer period of dull, aching pain in
the back, and no fever. Some patients note pain in the
chest, abdomen, arm, or leg. This occurs when the
inflammation in the spine causes pressure on a nerve
root serving one of these other areas. The lower back is
the most common location for osteomyelitis. When
caused by tuberculosis, osteomyelitis usually affects
the thoracic spine (that section of the spine running
approximately from the base of the neck down to
where the ribs stop).
When osteomyelitis is not properly treated, a
chronic (long-term) type of infection may occur. In
this case, the infection may wax and wane indefinitely,
despite treatment during its active phases. An abnormal opening in the skin overlaying the area of bone
infection (called a sinus tract) may occasionally drain
pus. This type of smoldering infection may also result
in areas of dead bone, called sequestra. These areas
occur when the infection interferes with blood flow to
2709

Osteomyelitis

OTHER

Osteopathy

a particular part of the bone. Such sequestra lack cells
called osteocytes, which in normal bone are continuously involved in the process of producing bony
material.

Diagnosis
Diagnosis of osteomyelitis involves several procedures. Blood is usually drawn and tested to demonstrate an increased number of the infection-fighting
white blood cells (particularly elevated in children
with acute osteomyelitis). Blood is also cultured in a
laboratory, a process which allows any bacteria present to multiply. A specimen from the culture is then
specially treated, and examined under a microscope to
try to identify the causative bacteria.
Injection of certain radioactive elements into the
bloodstream, followed by a series of x-ray pictures,
called a scan (radionuclide scanning), will reveal areas
of bone inflammation. Another type of scan used to
diagnose osteomyelitis is called magnetic resonance
imaging, or MRI
When pockets of pus are available, or overlaying
soft tissue infection exists, these can serve as sources
for samples which can be cultured to allow identification of bacteria present. A long, sharp needle can be
used to obtain a specimen of bone (biopsy), which can
then be tested to attempt to identify any bacteria
present.

Treatment
Antibiotics are medications used to kill bacteria.
These medications are usually given through a needle
in a vein (intravenously) for at least part of the time. In
children, these antibiotics can be given by mouth after
initial treatment by vein. In adults, four to six weeks
of intravenous antibiotic treatment is usually recommended, along with bed-rest for part or all of that
time. Occasionally, a patient will have such extensive
ostemyelitis that surgery will be required to drain any
pockets of pus, and to clean the infected area.

KEY TERMS
Abscess—A pus-filled pocket of infection.
Femur—The thighbone.
Humerus—The bone of the upper arm.
Thoracic—Pertaining to the area bounded by the
rib cage.
Tibia—One of the two bones of the lower leg.

myrrh (Commiphora molmol ) are all suggested for
infections. Juice therapists recommend drinking combinations of carrot, celery, beet, and cantaloupe juices.
A variety of homeopathic remedies may be helpful,
especially those used to counter inflammation.

Prognosis
Prognosis varies depending on how quickly an
infection is identified, and what other underlying conditions exist to complicate the infection. With quick,
appropriate treatment, only about 5% of all cases of
acute osteomyelitis will eventually become chronic
osteomyelitis. Patients with chronic osteomyelitis may
require antibiotics periodically for the rest of their lives.

Prevention
About the only way to have any impact on the
development of osteomyelitis involves excellent care of
any wounds or injuries.
Resources
PERIODICALS

Calhoun, Jason H., et al. ‘‘Osteomyelitis: Diagnosis,
Staging, Management.’’ Patient Care 32 (January 30,
1998): 93+.

Rosalyn Carson-DeWitt, MD

Osteopathic medicine see Osteopathy
Alternative treatment
General recommendations for the treatment of
infections include increasing vitamin supplements,
such as vitamins A and C. Liquid garlic extract is
sometimes suggested. Guided imagery can help induce
relaxation and improve pain, both of which are considered to improve healing. Herbs such as echinacea
(Echinacea spp.), goldenseal (Hydrastis canadensis),
Siberian ginseng (Eleutherococcus senticosus), and
2710

Osteopathy
Definition
Osteopathy is a system and philosophy of health
care that separated from traditional (allopathic) medical practice about a century ago. It places emphasis on
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
Osteopathy shares many of the same goals as
traditional medicine, but places greater emphasis on
the relationship between the organs and the musculoskeletal system as well as on treating the whole individual rather than just the disease.

Precautions
Pain is the chief reason patients seek musculoskeletal treatment. Pain is a symptom, not a disease
by itself. Of critical importance is first to determine
the cause of the pain. Cancers, brain or spinal cord
disease, and many other causes may be lying beneath
this symptom. Once it is clear that the pain is originating in the musculoskeletal system, treatment that
includes manipulation is appropriate.

Description
History
Osteopathy was founded in the 1890s by
Dr. Andrew Taylor, who believed that the musculoskeletal system was central to health. The primacy of
the musculoskeletal system is also fundamental to
chiropractic, a related health discipline. The original
theory behind both approaches presumed that energy
flowing through the nervous system is influenced by
the supporting structure that encase and protect it—
the skull and vertebral column. A defect in the musculoskeletal system was believed to alter the flow of this
energy and cause disease. Correcting the defect cured
the disease. Defects were thought to be misalignments—parts out of place by tiny distances. Treating
misalignments became a matter of restoring the parts
to their natural arrangement by adjusting them.
As medical science advanced, defining causes of
disease and discovering cures, schools of osteopathy
adopted modern science, incorporated it into their
curriculum, and redefined their original theory of
disease in light of these discoveries. Near the middle
of the 20th century the equivalance of medical education between osteopathy and allopathic medicine
was recognized, and the D.O. degree (Doctor of
Osteopathy) was granted official parity with the
GALE ENCYCLOPEDIA OF MEDICINE

M.D. (Doctor of Medicine) degree. Physicians could
adopt either set of initials.
However, osteopaths have continued their
emphasis on the musculoskeletal system and their traditional focus on ‘‘whole person’’ medicine. As of
1998, osteopaths constitute 5.5% of American physicians, approximately 45,000. They provide 100 million
patient visits a year. From its origins in the United
States, osteopathy has spread to countries all over the
world.
Practice
Osteopaths, chiropractors, and physical therapists are the experts in manipulations (adjustments).
The place of manipulation in medical care is far from
settled, but millions of patients find relief from it.
Particularly backs, but also necks, command most of
the attention of the musculoskeletal community. This
community includes orthopedic surgeons, osteopaths,
general and family physicians, orthopedic physicians,
chiropractors, physical therapists, massage therapists,
specialists in orthotics and prosthetics, and even some
dentists and podiatrists. Many types of headaches also
originate in the musculoskeletal system. Studies comparing different methods of treating musculoskeletal
back, head, and neck pain have not reached a consensus, in spite of the huge numbers of people that suffer
from it.
The theory behind manipulation focuses on
joints, mostly those of the vertebrae and ribs. Some
believe there is a very slight offset of the joint members—a subluxation. Others believe there is a vacuum
lock of the joint surfaces, similar to two suction cups
stuck together. Such a condition would squeeze joint
lubricant out and produce abrasion of the joint surfaces with movement. Another theory focuses on
weakness of the ligaments that support the joint,
allowing it freedom to get into trouble. Everyone
agrees that the result produces pain, that pain produces muscle spasms and cramps, which further aggravates the pain.
Some, but not all, practitioners in this field believe
that the skull bones can also be manipulated. The skull
is, in fact, several bones that are all moveable in
infants. Whether they can be moved in adults is controversial. Other practitioners manipulate peripheral
joints to relieve arthritis and similar afflictions.
Manipulation returns the joint to its normal configuration. There are several approaches. Techniques
vary among practitioners more than between disciplines. Muscle relaxation of some degree is often
required for the manipulation to be successful. This
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Osteopathy

the musculoskeletal system, hence the name—osteo
refers to bone and path refers to disease. Osteopaths
also believe strongly in the healing power of the body
and do their best to facilitate that strength. During this
century, the disciplines of osteopathy and allopathic
medicine have been converging.

Osteopetroses

KEY TERMS
Orthotics—Mechanical devices that assist function.
Prosthetics—Mechanical devices that replace
missing body parts.

to rehabilitate muscles, correct posture, and extinguish habits that arose to compensate for the pain.
Medications that relieve muscle spasm and pain are
usually part of the treatment. Psychological problems
may need attention and medication.

Risks
Manipulation has rarely caused problems. Once
in a while too forceful a thrust has damaged structures
in the neck and caused serious problems. The most
common adverse event, though, is misdiagnosis.
Cancers have been missed; surgical back disease has
been ignored until spinal nerves have been permanently damaged.
Osteopathic physician demonstrating the articulation of a
foot. (Photo Researchers, Inc. Reproduced by permission.)

can be done with heat or medication. Muscles can also
be induced to relax by gentle but persistent stretching.
The manipulation is most often done by a short, fast
motion called a thrust, precisely in the right direction.
A satisfying ‘‘pop’’ is evidence of success. Others prefer steady force until relaxation permits movement.
Return of the joint to its normal status may be
only the first step in treating these disorders. There is a
reason for the initial event. It may be a fall, a stumble,
or a mild impact, in which case the manipulation is a
cure. On the other hand, there may be a postural
misalignment (such as a short leg), a limp, or a
stretched ligament that permits the joint to slip back
into dysfunction. Tension, as well as pain, for emotional reasons causes muscles to tighten. If the pain
has been present for any length of time, there will also
be muscle deterioration. The osteopathic approach to
the whole person takes all these factors into account in
returning the patient to a state of health.
Other repairs may be needed. A short leg is
thought by some to be a subluxation in the pelvis
that may be manipulated back into position. Other
short legs may require a lift in one shoe. Long-standing
pain requires additional methods of physical therapy
2712

Normal results
Many patients find that one or a series of manipulations cures long-standing pain. Other patients
need repeated treatments. Some do not respond at
all. It is always a good idea to reassess any treatment
that is not producing the expected results.
Resources
ORGANIZATIONS

American Association of Colleges of Osteopathic Medicine.
5550 Friendship Blvd., Suite 310, Chevy Chase, MD
20815-7231. (301) 968-4100. <http://
www.aacom.org>.
American Osteopathic Association. <osteomed@wwa.com>
<http://www.am-osteo-assn.org>.

J. Ricker Polsdorfer, MD

Osteopetroses
Definition
Osteopetrosis (plural osteopetroses) is a rare hereditary disorder that makes bones increase in both
density and fragility. A potentially fatal condition
GALE ENCYCLOPEDIA OF MEDICINE

Description
Osteopetrosis occurs when bones are spongy or
porous, or new bone is repeatedly added to calcified
cartilage (hardened connective tissue).
Bone density begins to increase at birth or earlier,
but symptoms may not become evident until adulthood. In mild cases, bone density increases at gradual,
irregular intervals until full adult height is attained.
Some bones are not affected.
More severe osteopetrosis progresses at a rapid
pace and destroys bone structure. This condition
involves bones throughout the body, but the lower
jaw is never affected.

anemia. Infection results when excess bone impairs
the immune system, and hemorrhage can occur when
platelet production is disrupted. When the skeleton
grows so thick that nerves are unable to pass between
bones, the patient may have a stroke or become blind
or deaf.
Other symptoms associated with osteopetrosis
include:


bones that break easily and do not heal properly



bruising



convulsions



enlargement of the liver, lymph glands, or spleen



failure to thrive (delayed growth, weight gain, and
development)



hydrocephalus (fluid on the brain)



macrocephaly (abnormal enlargement of the head)



paralysis or loss of control of muscles in the face
or eyes

Types of osteopetroses
In early-onset osteopetrosis ends of the long bones
of the arms and legs appear clubbed (widened and
thickened) at birth, and bone density continues to
increase sporadically or without pause. Early-onset
osteopetroses can be a fatal condition, resulting in
death before the age of two.
Malignant infantile osteopetrosis is most often
discovered by the time a baby is a few months old.
One-third of all malignant infantile osteopetroses
cases result in death before the age of 10.
Intermediate osteopetrosis generally appears in
children under 10. This condition, usually less severe
than early-onset or malignant infantile osteopetrosis,
is not life-threatening.

Diagnosis
Osteopetrosis is usually diagnosed when x rays
reveal abnormalities or increases in bone density.
Bone biopsy can confirm the presence of osteopetrosis,
but additional tests may be needed to distinguish one
type of the disorder from another.

Treatment

Symptoms of adult or delayed-onset osteopetrosis
may not become evident until the child becomes a
teenager or adult.

High doses of vitamin D can stimulate cells
responsible for disintegration of old bone and significantly alleviate symptoms of severe disease.
Experimental interferon gamma 1-b therapy has been
shown to reduce the risk of infection experienced by
patients who are severely ill.

Relatively common in many parts of the world,
Albers-Schönberg disease is a mild form of this condition. People who have this disease are born with
normal bone structure. Bone density increases as
they age but does not affect appearance, health, intelligence, or life span.

When bone overgrowth deforms the shape of the
skull, surgery may be required to relieve pressure
on the brain. Orthodontic treatment is sometimes
necessary to correct malocclusion (a condition that
shifts the position of the teeth and makes closing the
mouth impossible).

Causes and symptoms
Osteopetrosis is the result of a genetic defect that
causes the body to add new bone more rapidly than
existing bone disintegrates.
When fibrous or bony tissue invades bone marrow
and displaces red blood cells, the patient may develop
GALE ENCYCLOPEDIA OF MEDICINE

Professional counseling can help patients cope
with the emotional aspects of deformed features.
Bone marrow transplants (BMT) have cured
some cases of early-onset and malignant infantile
osteopetrosis. Because 30–60% of children who
undergo BMT do not survive, this procedure is rarely
performed.
2713

Osteopetroses

that can deform bone structure and distort the appearance, osteopetrosis is also called chalk bones, ivory
bones, or marble bones.

Osteoporosis

strength, is decreased. As a result, bones become
fragile and break easily. Even a sneeze or a sudden
movement may be enough to break a bone in someone
with severe osteoporosis.

Description
Osteoporosis is a serious public health problem.
Some 44 million people in the United States are at risk
for this potentially debilitating disease, which is
responsible for 1.5 million fractures (broken bones)
annually. These fractures, which are often the first
sign of the disease, can affect any bone, but the most
common locations are the hip, spine, and wrist. Breaks
in the hip and spine are of special concern because they
almost always require hospitalization and major surgery, and may lead to other serious consequences,
including permanent disability and even death.

This infant has osteopetrosis, a condition which thickens and
hardens the bone. (Custom Medical Stock Photo. Reproduced
by permission.)

Prognosis
The severity of anemia seems to determine the
course of an individual’s osteopetrosis. When pronounced symptoms are present at the time of birth,
the child’s condition deteriorates rapidly. Death usually
occurs within two years. When mild or moderate disease develops in older children or adults and symptoms
can be controlled, the patient is likely to survive.
Resources
ORGANIZATIONS

Osteoporosis and Related Bone Diseases-National Resource
Center. 1150 17th S. NW, Ste. 500, Washington, DC
20036. (800) 624-2663.

Maureen Haggerty

Osteoporosis
Definition
The word osteoporosis literally means ‘‘porous
bones.’’ It occurs when bones lose an excessive amount
of their protein and mineral content, particularly calcium. Over time, bone mass, and therefore bone
2714

To understand osteoporosis, it is helpful to understand the basics of bone formation. Bone is living
tissue that is constantly being renewed in a two-stage
process (resorption and formation) that occurs
throughout life. In the resorption stage, old bone is
broken down and removed by cells called osteoclasts.
In the formation stage, cells called osteoblasts build
new bone to replace the old. During childhood and
early adulthood, more bone is produced than
removed, reaching its maximum mass and strength
by the mid-30s. After that, bone is lost at a faster
pace than it is formed, so the amount of bone in the
skeleton begins to slowly decline. Most cases of osteoporosis occur as an acceleration of this normal aging
process, which is referred to as primary osteoporosis.
The condition also can be caused by other disease
processes or prolonged use of certain medications
that result in bone loss. If so, this is called secondary
osteoporosis.
Osteoporosis occurs most often in older people and
in women after menopause. It affects nearly half of men
and women over the age of 75. Women are about five
times more likely than men to develop the disease. They
have smaller, thinner bones than men to begin with,
and they lose bone mass more rapidly after menopause
(usually around age 50), when they stop producing a
bone-protecting hormone called estrogen. In the five to
seven years following menopause, women can lose
about 20% of their bone mass. By age 65 or 70, though,
men and women lose bone mass at the same rate. As an
increasing number of men reach an older age, there is
more awareness that osteoporosis is an important
health issue for them as well. In fact, a 2003 report
noted that one in every eight men over age 50 will suffer
a hip fracture as a result of osteoporosis.
GALE ENCYCLOPEDIA OF MEDICINE

A number of factors increase the risk of developing osteoporosis. They include:


Age. Osteoporosis is more likely as people grow
older and their bones lose tissue.



Gender. Women are smaller and start out with
less bone. They also lose bone tissue more rapidly
as they age. While women commonly lose 30–50% of
their bone mass over their lifetimes, men lose only
20–33%.



Race. Caucasian and Asian women are most at risk
for the disease, but African American and Hispanic
women can get it too.



Figure type. Women with small bones and those who
are thin are more liable to have osteoporosis.



Early menopause. Women who stop menstruating
early because of heredity, surgery or lots of physical
exercise may lose large amounts of bone tissue
early in life. Conditions such as anorexia and bulimia also may lead to early menopause and
osteoporosis.



Lifestyle. People who smoke or drink too much, or
do not get enough exercise have an increased chance
of osteoporosis.



Diet. Those who do not get enough calcium or protein may be more likely to have osteoporosis. That is
why people who constantly diet are more prone to
the disease.



Genetics. Research in Europe reported in 2003 that
variations of a gene on chromosome 20 might make
some postmenopausal women more likely to have
osteoporosis. Studies were continuing on how to
identify the gene and use information from the
research to prevent osteoporosis in carriers.

Osteoporosis is often called the ‘‘silent’’ disease,
because bone loss occurs without symptoms. People
often do not know they have the disease until a bone
breaks, frequently in a minor fall that would not
normally cause a fracture. A common occurrence is
compression fractures of the spine. These can happen
even after a seemingly normal activity, such as bending or twisting to pick up a light object. The fractures
can cause severe back pain, but sometimes go unnoticed—either way, the vertebrae collapse down on
themselves, and the person actually loses height.
The hunchback appearance of many elderly women,
sometimes called ‘‘dowager’s’’ hump or ‘‘widow’s’’
hump, is due to this effect of osteoporosis on the
vertebrae.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Certain types of doctors may have more training
and experience than others in diagnosing and treating
people with osteoporosis. These include a geriatrician,
who specializes in treating the aged; an endocrinologist, who specializes in treating diseases of the body’s
endocrine system (glands and hormones); and an
orthopedic surgeon, who treats fractures such as
those caused by osteoporosis.
Before making a diagnosis of osteoporosis, the
doctor usually takes a complete medical history, conducts a physical exam, and orders x rays, as well as
blood and urine tests, to rule out other diseases that
cause loss of bone mass. The doctor also may recommend a bone density test. This is the only way to know
for certain if osteoporosis is present. It also can show
how far the disease has progressed.
Several diagnostic tools are available to measure
bone density. The ordinary x ray is one, though it is the
least accurate for early detection of osteoporosis,
because it does not reveal bone loss until the disease is
advanced and most of the damage has already been
done. Two other tools that are more likely to catch
osteoporosis at an early stage are computed tomography
scans (CT scans) and machines called densitometers,
which are designed specifically to measure bone density.
The CT scan, which takes a large number of x rays
of the same spot from different angles, is an accurate
test, but uses higher levels of radiation than other
methods. The most accurate and advanced of the
densitometers uses a technique called DEXA (dual
energy x-ray absorptiometry). With the DEXA scan,
a double x-ray beam takes pictures of the spine, hip, or
entire body. It takes about 20 minutes to do, is painless, and exposes the patient to only a small amount of
radiation—about one-fiftieth that of a chest x ray.
Doctors do not routinely recommend the test,
partly because access to densitometers is still not
widely available. People should talk to their doctors
about their risk factors for osteoporosis and if, and
when, they should get the test. Ideally, women should
have bone density measured at menopause, and periodically afterward, depending on the condition of
their bones. Men should be tested around age 65.
Men and women with additional risk factors, such as
those who take certain medications, may need to be
tested earlier.

Treatment
There are a number of good treatments for
primary osteoporosis, most of them medications.
2715

Osteoporosis

Causes and symptoms

Osteoporosis

Two medications, alendronate and calcitonin (in nose
spray form), have been approved by the Food and
Drug Administration (FDA). They provide people
who have osteoporosis with a variety of choices for
treatment. For people with secondary osteoporosis,
treatment may focus on curing the underlying disease.
Drugs
For many women who have gone through menopause, the treatment of choice for osteoporosis has
been hormone replacement therapy (HRT), also called
estrogen replacement therapy. Many women choose
HRT when they undergo menopause to alleviate
symptoms such as hot flashes, but hormones increase
a woman’s supply of estrogen, which helps build new
bone, while preventing further bone loss. A 2002
report from a large clinical trial called the Women’s
Health Initiative helped verify HRT’s positive effects
in preventing osteoporosis in postmenopausal women.
However, the WHI also revealed several risks with
taking combined HRT (estrogen and progesterone).
In fact, the trial was stopped early because the incidence of invasive breast cancer in women on HRT
passed a threshold that was considered too risky for
the benefits they were receiving. The study also found
that the women on combined hormone therapy were
at increased risk for coronary heart disease and stroke.
Whether or not a woman takes hormones and for how
long is a decision she should make carefully with her
doctor. Women should talk to their doctors about
personal risks for osteoporosis, as well as their risks
for heart disease and breast cancer.
Since estrogen may no longer be recommended
for prevention of osteoporosis, selective use of alendronate and calcitonin are possible alternatives.
Alendronate and calcitonin both stop bone loss, help
build bone, and decrease fracture risk by as much as
50%. Alendronate (sold under the name Fosamax) is
the first nonhormonal medication for osteoporosis
ever approved by the FDA. It attaches itself to bone
that has been targeted by bone-eating osteoclasts,
protecting the bone from these cells. Osteoclasts help
the body break down old bone tissue.
Calcitonin is a hormone that has been used as an
injection for many years. A new version is on the
market as a nasal spray. It too slows down bone-eating
osteoclasts.
Side effects of these drugs are minimal, but calcitonin builds bone by only 1.5% a year, which may not
be enough for some women to recover the bone they
lose. Fosamax has proven safe in large, multi-year
studies, but not much is known about the effects of
2716

A scanning electron microscopy (SEM) image of cancellous
(spongy) bone from an osteoporosis patient. Osteoporosis is
characterized by increased brittleness of the bones and a
greater risk of fractures. This is reflected here in the thin
appearance of the bony network of the cancellous bone that
forms the core of the body’s long bones. (Photograph by
Professor P. Motta, Photo Researchers, Inc. Reproduced by
permission.)

its long-term use. Several medications under study
include other bisphosphonates that slow bone breakdown (like alendronate), sodium fluoride, vitamin D
metabolites, and selective estrogen receptor modulators. Some of these treatments are already being used
in other countries, but have not yet been approved by
the FDA for use in the United States.
In early 2003, a report announced that the FDA
had recently approved the first drug that could form
bone in osteoporosis patients. The drug is a form of
the human parathyroid hormone called teriparatide. It
shows promise for those patients at highest risk for
fracture from the disease. There are some patients who
cannot use the drug, so all considering the new
GALE ENCYCLOPEDIA OF MEDICINE

Surgery
Unfortunately, much of the treatment for osteoporosis is for fractures that result from advanced
stages of the disease. For complicated fractures, such
as broken hips, hospitalization and a surgical procedure are required. In hip replacement surgery, the
broken hip is removed and replaced with a new hip
made of plastic, or metal and plastic. Though the
surgery itself is usually successful, complications of
the hip fracture can be serious. Those individuals
have a 5–20% greater risk of dying within the first
year following the injury than do others in their age
group. A large percentage of those who survive are
unable to return to their previous level of activity, and
many move self-care to a supervised living situation or
nursing home. That is why getting early treatment and
taking steps to reduce bone loss are vital.

Alternative treatment
Alternative treatments for osteoporosis focus on
maintaining or building strong bones. A healthy diet
low in fats and animal products and containing whole
grains, fresh fruits and vegetables, and calcium-rich
foods (such as dairy products, dark-green leafy vegetables, sardines, salmon, and almonds), along with
nutritional supplements (such as calcium, magnesium,
and vitamin D), and weight-bearing exercises are
important components of both conventional prevention and treatment strategies and alternative
approaches to the disease. In addition, alternative
practitioners recommend a variety of botanical medicines or herbal supplements. Herbal supplements
designed to help slow bone loss emphasize the use
of calcium-containing plants, such as horsetail
(Equisetum arvense), oat straw (Avena sativa), alfalfa
(Medicago sativa), licorice (Glycyrrhiza galbra), marsh
mallow (Althaea officinalis), and yellow dock (Rumex
crispus). Homeopathic remedies focus on treatments
believed to help the body absorb calcium. These remedies are likely to include such substances as Calcarea
carbonica (calcium carbonate) or silica. In traditional
Chinese medicine, practitioners recommend herbs
thought to slow or prevent bone loss, including dong
quai (Angelica sinensis) and Asian ginseng (Panax
ginseng). Natural hormone therapy, using plant estrogens (from soybeans) or progesterone (from wild
yams), may be recommended for women who cannot
or choose not to take synthetic hormones.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
There is no cure for osteoporosis, but it can be
controlled. Most people who have osteoporosis fare
well once they receive treatment. The medicines available now build bone, protect against bone loss, and
halt the progress of this disease.

Prevention
Building strong bones, especially before the age of
35, and maintaining a healthy lifestyle are the best
ways to prevent osteoporosis. To build as much bone
mass as early as possible in life, and to help slow the
rate of bone loss later in life, doctors advise:
Getting calcium from foods
Experts recommend 1,500 milligrams (mg) of
calcium per day for adolescents, pregnant or breastfeeding women, older adults (over 65), and postmenopausal women not using hormone replacement
therapy. All others should get 1,000 mg per day. Foods
are the best source for this important mineral. Milk,
cheese, and yogurt have the highest amounts. Other
foods that are high in calcium are green leafy vegetables, tofu, shellfish, Brazil nuts, sardines, and
almonds.
Taking calcium supplements
Many people, especially those who do not like or
can not eat dairy foods, do not get enough calcium in
their diets and may need calcium supplements.
Supplements vary in the amount of calcium they contain.
Those with calcium carbonate have the most amount of
useful calcium. Supplements should be taken with meals
and accompanied by six to eight glasses of water a day.
Getting vitamin D
Vitamin D helps the body absorb calcium. People
can get vitamin D from sunshine with a quick (15–20
minute) walk each day or from foods such as liver,
fish oil, and vitamin-D fortified milk. During the winter months it may be necessary to take supplements.
Four hundred mg daily is usually the recommended
amount.
Avoiding smoking and alcohol
Smoking reduces bone mass, as does heavy drinking. Avoiding smoking and limiting alcoholic drinks
to no more than two per day reduces risks. An alcoholic drink is one-and-a-half ounces of hard liquor,
12 ounces of beer, or five ounces of wine.
2717

Osteoporosis

treatment must check with their physician and may
need to undergo bone densitometry scans or other
testing.

Ostomy

Resources

KEY TERMS
Alendronate—A nonhormonal drug used to treat
osteoporosis in postmenopausal women.
Anticonvulsants—Drugs used to control seizures,
such as in epilepsy.
Biphosphonates—Compounds (like alendronate)
that slow bone loss and increase bone density.
Calcitonin—A hormonal drug used to treat postmenopausal osteoporosis
Estrogen—A female hormone that also keeps bones
strong. After menopause, a woman may take hormonal drugs with estrogen to prevent bone loss.
Glucocorticoids—Any of a group of hormones (like
cortisone) that influence many body functions and
are widely used in medicine, such as for treatment
of rheumatoid arthritis inflammation.
Hormone replacement therapy (HRT)—Also
called estrogen replacement therapy, this controversial treatment is used to relieve the discomforts
of menopause. Estrogen and another female
hormone, progesterone, are usually taken together
to replace the estrogen no longer made by the
body.
Menopause—The ending of a woman’s menstrual
cycle, when production of bone-protecting estrogen decreases.
Osteoblasts—Cells in the body that build new
bone tissue.
Osteoclasts—Cells that break down and remove
old bone tissue.
Selective estrogen receptor modulator—A hormonal preparation that offers the beneficial effects of
hormone replacement therapy without the
increased risk of breast and uterine cancer associated with HRT.

Exercise
Exercising regularly builds and strengthens
bones. Weight-bearing exercises—where bones and
muscles work against gravity—are best. These
include aerobics, dancing, jogging, stair climbing,
tennis, walking, and lifting weights. People who
have osteoporosis may want to attempt gentle exercise, such as walking, rather than jogging or fastpaced aerobics, which increase the chance of falling.
Exercising three to four times per week for 20–30
minutes each time helps.
2718

PERIODICALS

Doering, Paul L. ‘‘Treatment of Menopause Post-WHI:
What Now?’’ Drug Topics April 21, 2003: 85.
Elliott, William T. ‘‘HRT, Estrogen, and
Postmenopausal Women: Year-old WHI Study
Continues to Raise Questions.’’ Critical Care Alert
July 2003: 1.
LoBuono, Charlotte. ‘‘New Osteoporosis Drug is First to
Form Bone.’’ Drug Topics January 6, 2003: 24.
‘‘More Men at Osteoporosis Risk than Commonly
Believed.’’ Tufts University Health and Nutrition Letter
August 2003: 8.
Nelson, Heidi D. ‘‘Postmenopausal Osteoporosis and
Estrogen.’’ American Family Physician August 15,
2003: 606.
‘‘Osteoporosis Gene Identified.’’ Diagnostics and Imaging
Week March 13, 2003 4.
‘‘Three Out of Four Women Currently Taking Prescriptions
for Osteoporosis Are Not Receiving Full Treatment,
According to Recent Data from a National Physician
Audit.’’ Drug Cost Management Report January
2003: 11.

Barbara Boughton
Teresa G. Odle

Osteosarcoma see Sarcomas

Ostomy
Definition
A surgical procedure creating an opening in the
body for the discharge of body wastes.

Purpose
Certain diseases of the bowel or urinary tract
involve removing all or part of the intestine or bladder.
This creates a need for an alternate way for feces
or urine to leave the body. An opening is surgically
created in the abdomen for body wastes to pass
through. The surgical procedure is called an ostomy.
The opening that is created at the end of the bowel or
ureter is called a stoma, which is pulled through the
abdominal wall.

Description
Different types of ostomy are performed depending on how much and what part of the intestines or
bladder is removed.
GALE ENCYCLOPEDIA OF MEDICINE



colostomy



ileostomy



urostomy
Colostomy

A colostomy is a when a small portion of the colon
(large intestine) is brought to the surface of the
abdominal wall to allow stool to be eliminated. A
colostomy may be temporary or permanent. A permanent colostomy usually involves the loss of the rectum.
A colostomy might be performed due to cancer,
diverticulitis, imperforate anus, Hirschsprung’s disease, or trauma to the affected area.
Ileostomy
An ileostomy is an opening created in the small
intestine to bypass the colon for stool elimination. The
end of the ileum, which is the lowest part of the small
intestine, is brought through the abdominal wall to
form a stoma.
Ileoanal reservoir surgery is an alternative to a
permanent ileostomy. It requires two surgical procedures. The first removes the colon and rectum and a
temporary ileostomy is created. The second procedure
creates an internal pouch from a portion of the small
intestine to hold stool. This is then attached to the
anus. Since the muscle of the rectum is left in place,
there is control over bowel movements.
An ileostomy might be performed due to ulcerative colitis, Crohn’s disease, or familial polyposis.
Urostomy
A urostomy is a surgical procedure that diverts
urine away from a diseased or defective bladder.
Among several methods to create the urostomy, the
most common method is called an ileal or cecal conduit. Either a section at the end of the small intestine
(ileum) or at the beginning of the large intestine
(cecum) is relocated surgically to form a stoma for
urine to pass out of the body. Other common names
for this procedure are ileal loop or colon conduit.
A urostomy may be performed due to bladder
cancer, spinal cord injuries, malfunction of the bladder, and birth defects such as spina bifida.
Since colostomy, ileostomy, and usotomy bypass
the sphincter muscle there is no voluntary control over
bowel movements and an external pouch must be
worn to catch the discharge.
GALE ENCYCLOPEDIA OF MEDICINE

Preparation

Ostomy

The three most common types of ostomies are:

Aftercare
The skin around the stoma, called the peristomal
skin, must be protected from direct contact with
discharge. The discharge can be irritating to the
stoma since it is very high in digestive enzymes. The
peristomal skin should be cleansed with plain soap and
rinsed with water at each change of the pouch.
The stoma can change in size due to weight gain/
loss or several other situations. To ensure proper fit of
discharge pouch the stoma should be measured each
time supplies are purchased.

Risks
People with ostomies can be prone to certain types
of skin infections. Skin irritations or rashes around the
stoma may be caused by leakage from around the
pouch due to an improperly fitted pouch. Correctly
fitting the pouch and carefully cleaning the skin
around the stoma after each change are the best ways
of preventing skin irritation.
Urinary tract infections are common among
people who have urostomies. Preventative measures
include drinking plenty of fluids, emptying the pouch
regularly and using a pouch with an anti-reflux valve
to prohibit the discharge from moving back into the
stoma.

Normal results
Most ostomy pouches are inconspicuous and can
be worn under almost any kind of clothing. There are
typically no restrictions of activity, sport, or travel
with an ostomy. Certain contact sports would warrant
special protection for the stoma.
After recovery from surgery, most people with
ostomies can resume a balanced diet.
Ostomy surgery does not generally interfere with
a person’s sexual or reproductive capacities.

Abnormal results
After an ileostomy, water and electrolyte loss may
occur. It may be necessary to drink a significant
amount of fluid or fruit juice each day to prevent
dehydration.
After any type of ostomy surgery digestion and
absorbtion of medications may also be affected.
High-fiber foods can cause blockages in the ileum,
especially after surgery. Chewing food well helps
2719

Otitis externa

KEY TERMS
Crohn’s disease—A chronic inflammatory disease,
primarily involving the small and large intestine,
but which can affect other parts of the digestive
system as well.
Diverticulitis—Inflammation of the diverticula
(small outpouchings) along the wall of the colon,
the large intestine.
Familial polyposis—An inherited condition in
which several hundred polyps develop in the
colon and rectum.
Hirschsprung disease—Hirschsprung disease is a
congenital abnormality (birth defect) of the bowel
in which there is absence of the ganglia (nerves)
in the wall of the bowel. Nerves are missing starting at the anus and extending a variable distance
up the bowel. This results in megacolon (massive
enlargement of the bowel) above the point where
the nerves are missing. (The nerves are needed to
assist in the natural movement of the muscles in
the lining of the bowels that move bowel contents
through.)
Ileum—The lowest part of the small intestine,
located beyond the duodenum and jejunum, just
before the large intestine (the colon).
Imperforate anus—A congenital malformation (a
birth defect) in which the rectum is a blind alley
(a cul-de-sac) and there is no anus.
Spina bifida—A birth defect (a congenital malformation) in which there is a bony defect in the
vertebral column so that part of the spinal cord,
which is normally protected within the vertebral
column, is exposed. People with spina bifida can
suffer from bladder and bowel incontinence, cognitive (learning) problems and limited mobility.

National Digestive Diseases Clearinghouse. 2 Information
Way, Bethesda, MD 20892-3570. <http://www.niddk.
nih.gov/>.
United Ostomy Association. 19772 MacArthur Boulevard,
Suite 200 Irvine, CA 92612-2405. (800) 826-0826 or
(949) 660-8624.

Gary Gilles

Otitis externa
Definition
Otitis externa refers to an infection of the ear
canal, the tube leading from the outside opening of
the ear in towards the ear drum.

Description
The external ear canal is a tube approximately 1 in
(2.5 cm) in length. It runs from the outside opening of
the ear to the start of the middle ear, designated by the
ear drum or tympanic membrane. The canal is partly
cartilage and partly bone. In early childhood, the first
two-thirds of the canal is made of cartilage, and the
last one-third is made of bone. By late childhood, and
lasting throughout all of adulthood, this proportion is
reversed, so that the first one-third is cartilage, and the
last two-thirds is bone. The lining of the ear canal
is skin, which is attached directly to the covering of
the bone. Glands within the skin of the canal produce
a waxy substance called cerumen (popularly called
earwax). Cerumen is designed to protect the ear
canal, repel water, and keep the ear canal too acidic
to allow bacteria to grow.

Causes and symptoms
break fiber into smaller pieces and makes it less likely
to accumulate at a narrow point in the bowel.
Drinking plenty of fluids can also help.
Resources
ORGANIZATIONS

Crohn’s & Colitis Foundation of America, Inc. 386 Park
Avenue South 17th Floor, New York, NY 10016-8804.
(800) 932-2423 or (212) 685-3440.
International Foundation for Functional Gastrointestinal
Disorders. P.O. Box 17864, Milwaukee, WI 53217.
(414) 964-1799.
2720

Bacteria, fungi, and viruses have all been implicated in causing ear infections called otitis externa.
The most common cause of otitis externa is bacterial
infection. The usual offenders include Pseudomonas
aeruginosa, Enterobacter aerogenes, Proteus mirabilis,
Klebsiella pneumoniae, Staphylococcus epidermidis,
and bacteria of the family called Streptococci.
Occasionally, fungi may cause otitis externa. These
include Candida and Aspergillus. Two types of viruses,
called herpesvirus hominis and varicella-zoster virus,
have also been identified as causing otitis externa.
Otitis externa occurs most often in the summer
months, when people are frequenting swimming pools
GALE ENCYCLOPEDIA OF MEDICINE

Otitis externa

and lakes. Continually exposing the ear canal to
moisture may cause significant loss of cerumen. The
delicate skin of the ear canal, unprotected by cerumen,
retains moisture and becomes irritated. Without cerumen, the ear canal stops being appropriately acidic,
which allows bacteria the opportunity to multiply.
Thus, the warm, moist, dark environment of the ear
canal becomes a breeding ground for bacteria.
Other conditions predisposing to otitis externa
include the use of cotton swabs to clean the ear canals.
This pushes cerumen and normal skin debris back into
the ear canal, instead of allowing the ear canal’s normal cleaning mechanism to work, which would ordinarily move accumulations of cerumen and debris out
of the ear. Also, putting other items into the ear can
scratch the canal, making it more susceptible to
infection.
The first symptom of otitis externa is often itching
of the ear canal. Eventually, the ear begins to feel
extremely painful. Any touch, movement, or pressure
on the outside structure of the ear (auricle) may cause
quite severe pain. This is because of the way in which
the skin lining the ear canal is directly attached to the
covering of the underlying bone. If the canal is sufficiently swollen, hearing may become muffled. The
canal may appear swollen and red, and there may be
evidence of greenish-yellow pus.
In severe cases, otitis externa may have an accompanying fever. Often, this indicates that the outside ear
structure (auricle) has become infected as well. It will
become red and swollen, and there may be enlarged
and tender lymph nodes in front of, or behind, the
auricle.
A serious and life-threatening otitis externa is
called malignant otitis externa. This is an infection
which most commonly affects patients who have diabetes, especially the elderly. It can also occur in other
patients who have weakened immune systems. In
malignant otitis externa, a patient has usually had
minor symptoms of otitis externa for some months,
with pain and drainage. The causative bacteria is
usually Pseudomonas aeruginosa. In malignant otitis
externa, this bacteria spreads from the external canal
into all of the nearby tissues, including the bones of the
skull. Swelling and destruction of these tissues may
lead to damage of certain nerves, resulting in spasms
of the jaw muscles or paralysis of the facial muscles.
Other, more severe, complications of this very destructive infection include meningitis (swelling and infection of the coverings of the spinal cord and brain),
brain infection, or brain abscess (the development of
a pocket of infection with pus).
GALE ENCYCLOPEDIA OF MEDICINE

A close-up image of the ear of an elderly man suffering
from non-infectious otitis externa. The skin in the ear canal
and outer ear is scaly. (Photograph by Dr. P. Marazzi, Custom
Medical Stock Photo. Reproduced by permission.)

Diagnosis
Diagnosis of uncomplicated otitis externa is
usually quite simple. The symptoms alone, of ear
pain worsened by any touch to the auricle, are characteristic of otitis externa. Attempts to examine the ear
canal will usually reveal redness and swelling. It may
be impossible (due to pain and swelling) to see much
of the ear canal, but this inability itself is diagnostic.
If there is any confusion about the types of
organisms causing otitis externa, the canal can be
gently swabbed to obtain a specimen. The organisms
present in the specimen can then be cultured (allowed
to multiply) in a laboratory, and then viewed under a
microscope to allow identification of the causative
organisms.
If the rare disease malignant otitis externa is
suspected, computed tomography scan (CT scan) or
2721

Otitis media

magnetic resonance imaging (MRI) scans will be performed to determine how widely the infection has
spread within bone and tissue. A swab of the external
canal will not necessarily reveal the actual causative
organism, so some other tissue sample (biopsy) will
need to be obtained. The CT or MRI will help the
practitioner decide where the most severe focus of
infection is located, in order to guide the choice of a
biopsy site.

Treatment
Antibiotics which can be applied directly to the
skin of the ear canal (topical antibiotics) are usually
excellent for treatment of otitis externa. These are
often combined in a preparation which includes a
steroid medication. The steroid helps cut down on
the inflammation and swelling within the ear canal.
Some practitioners prefer to insert a cotton wick into
the ear canal, leaving it there for about 48 hours. The
medications are applied directly to the wick, enough
times per day to allow the wick to remain continuously
saturated. After the wick is removed, the medications
are then put directly into the ear canal three to four
times each day.
In malignant otitis externa, antibiotics will almost
always need to be given through a needle in the vein
(intravenously or IV). If the CT or MRI scan reveals
that the infection has spread extensively, these IV
antibiotics will need to be continued for six to eight
weeks. If the infection is in an earlier stage, two weeks
of IV antibiotics can be followed by six weeks of antibiotics by mouth.

Prognosis
The prognosis is excellent for otitis externa. It is
usually easily treated, although it may tend to recur in
certain susceptible individuals. Left untreated, malignant otitis externa may spread sufficiently to cause
death.

Prevention
Keeping the ear dry is an important aspect of
prevention of otitis externa. Several drops of a mixture
of alcohol and acetic acid can be put into the ear canal
after swimming to insure that it dries adequately.
The most serious complications of malignant
otitis externa can be avoided by careful attention to
early symptoms of ear pain and drainage from the
ear canal. Patients with conditions that put them at
higher risk for this infection (diabetes, conditions
2722

KEY TERMS
Auricle—The external structure of the ear.
Biopsy—The removal and examination, usually
under a microscope, of tissue from the living
body. Used for diagnosis.
Cerumen—Earwax.

which weakened the immune system) should always
report new symptoms immediately.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.

Rosalyn Carson-DeWitt, MD

Otitis media
Definition
Otitis media is an infection of the middle ear
space, behind the eardrum (tympanic membrane). It
is characterized by pain, dizziness, and partial loss of
hearing.

Description
A little knowledge of the basic anatomy of the
middle ear will be helpful for understanding the development of otitis media. The external ear canal is that
tube which leads from the outside opening of the ear to
the structure called the tympanic membrane. Behind
the tympanic membrane is the space called the middle
ear. Within the middle ear are three tiny bones, called
ossicles. Sound (in the form of vibration) causes movement in the eardrum, and then the ossicles. The ossicles transmit the sound to a structure within the inner
ear, which sends it to the brain for processing.
The nasopharynx is that passageway behind the
nose which takes inhaled air into the breathing tubes
leading to the lungs. The eustachian tube is a canal
which runs between the middle ear and the nasopharynx. One of the functions of the eustachian tube is to
keep the air pressure in the middle ear equal to that
GALE ENCYCLOPEDIA OF MEDICINE

By age three, almost 85% of all children will have
had otitis media at least once. Babies and children
between the ages of six months and six years are
most likely to develop otitis media. Children at higher
risk factors for otitis media include boys, children
from poor families, Native Americans, Native
Alaskans, children born with cleft palate or other
defects of the structures of the head and face, and
children with Down syndrome. Exposure to cigarette
smoke significantly increases the risk of otitis media
as well as other problems affecting the respiratory
system. Also, children who enter daycare at an early
age have more upper respiratory infections (URIs or
colds), and thus more cases of otitis media. The most
usual times of year for otitis media to strike are in
winter and early spring (the same times URIs are
most common).
Otitis media is an important problem, because it
often results in fluid accumulation within the middle
ear (effusion). The effusion can last for weeks to
months. Effusion within the middle ear can cause
significant hearing impairment. When such hearing
impairment occurs in a young child, it may interfere
with the development of normal speech.
In adults, acute otitis media can lead to such
complications as paralysis of the facial nerves.
Recovery from these complications may take from
two weeks to as long as three months.

organisms) is better able to reach the middle ear.
Children also have a lot of lymph tissue (commonly
called the adenoids) in the area of the eustachian tube.
These adenoids may enlarge with repeated respiratory
tract infections (colds), ultimately blocking the eustachian tubes. When the eustachian tube is blocked, the
middle ear is more likely to fill with fluid. This fluid,
then, increases the risk of infection, and the risk of
hearing loss and delayed speech development.
Most cases of acute otitis media occur during the
course of a URI. Symptoms include fever, ear pain,
and problems with hearing. Babies may have difficulty
feeding. When significant fluid is present within the
middle ear, pain may increase depending on position.
Lying down may cause an increase in painful pressure
within the middle ear, so that babies may fuss if not
held upright. If the fluid build-up behind the eardrum
is sufficient, the eardrum may develop a hole (perforate), causing bloody fluid or greenish-yellow pus to
drip from the ear. Although pain may be significant
leading up to such a perforation, the pain is usually
relieved by the reduction of pressure brought on by a
perforation.
Recent advances in gene mapping have led to the
discovery of genetic factors that increase a child’s
susceptibility to otitis media. Researchers are hoping
to develop molecular diagnostic assays that will help
to identify children at risk for severe ear infections.

Diagnosis

The first precondition for the development of
acute otitis media is exposure to an organism capable
of causing the infection. Otitis media can be caused
by either viruses or bacteria. Virus infections account
for about 15% of cases. The three most common
bacterial pathogens are Streptococcus pneumoniae,
Haemophilus influenzae, or Moraxella catarrhalis.
As of 2003, about 75% of ear infections caused by
S. pneumoniae are reported to be penicillin-resistant.

Diagnosis is usually made simply by looking at the
eardrum through a special lighted instrument called an
otoscope. The eardrum will appear red and swollen,
and may appear either abnormally drawn inward, or
bulging outward. Under normal conditions, the ossicles create a particular pattern on the eardrum,
referred to as ‘‘landmarks.’’ These landmarks may be
obscured. Normally, the light from the otoscope
reflects off of the eardrum in a characteristic fashion.
This is called the ‘‘cone of light.’’ In an infection, this
cone of light may be shifted or absent.

Otitis media may also be caused by other disease
organisms, including Bordetella pertussis, the causative agent of whooping cough, and Pneumocystis
carinii, which often causes opportunistic infections in
patients with AIDS.

A special attachment to the otoscope allows a puff
of air to be blown lightly into the ear. Normally, this
should cause movement of the eardrum. In an infection, or when there is fluid behind the eardrum, this
movement may be decreased or absent.

There are other factors which make the development of an ear infection more likely. Because the
eustachian tube has a more horizontal orientation
and is considerably shorter in early childhood, material
from the nasopharynx (including infection-causing

If fluid or pus is draining from the ear, it can be
collected. This sample can then be processed in a
laboratory to allow any organisms present to multiply
sufficiently (cultured) to permit the organisms to be
viewed under a microscope and identified.

Causes and symptoms

GALE ENCYCLOPEDIA OF MEDICINE

2723

Otitis media

outside. This allows the eardrum and ossicles to
vibrate appropriately, so that hearing is normal.

Otitis media

Middle ear
Semicircular canals

Cochlea

Stapes
Fluid
Incus
Eardrum

Malleus

Eustachian tube

Otitis media is an ear infection in which fluid accumulates within the middle ear. A common condition occurring in childhood, it
is estimated that 85% of all American children will develop otitis media at least once. (Illustration by Electronic Illustrators Group.)

Treatment
Medications
Antibiotics are the treatment of choice for acute
otitis media (AOM). Different antibiotics are used
depending on the type of bacteria most likely to be
causing the infection. This decision involves knowledge of the types of antibiotics that have worked on
other ear infections occurring within a particular community at a particular time. Options include sulfabased antibiotics, as well as a variety of penicillins,
cephalosporins, and others. The patient’s sensitivity
to certain medications, as well as previously demonstrated resistant strains, also contributes to the choice
of antibiotic. As of 2003, an 0.3% topical solution of
ofloxacin has been recommended as a more effective
medication than other oral or topical antibiotics.
Some controversy exists regarding whether overuse of antibiotics is actually contributing to the development of bacteria, which may evolve and become
2724

able to avoid being killed by antibiotics. Research is
being done to try to help determine whether there
may be some ear infections that will clear up without
antibiotic treatment. In the meantime, the classic
treatment of an ear infection continues to involve a
seven to 10-day course of antibiotic medication.
Some medical practitioners prescribe the use of
special nosedrops, decongestants, or antihistamines to
improve the functioning of the eustachian tube.
Whether or not antibiotics are used, such pain
relievers as Tylenol or Motrin can be very helpful in
reducing the pain and inflammation associated with
otitis media.
Surgery
In a few rare cases, a surgical perforation to drain
the middle ear of pus may be performed. This procedure is called a myringotomy. The hole created by the
myringotomy generally heals itself in about a week.
GALE ENCYCLOPEDIA OF MEDICINE

Although some doctors have recommended
removing the adenoids to prevent recurrent otitis
media in young children, recent studies indicate that
surgical removal of the adenoids does not appear to
offer any advantages over a myringotomy as a preventive measure.

Alternative treatment
Some practitioners believe that food allergies may
increase the risk of ear infections, and they suggest
eliminating suspected food allergens from the diet.
The top food allergens are wheat, dairy products,
corn, peanuts, citrus fruits, and eggs. Elimination
of sugar and sugar products can allow the immune
system to work more effectively. A number of herbal
treatments have been recommended, including ear
drops made with goldenseal (Hydrastis canadensis),
mullein (Verbascum thapsus), St. John’s wort
(Hypericum perforatum), and echinacea (Echinacea
spp.). Among the herbs often recommended for oral
treatment of otitis media are echinacea and cleavers
(Galium aparine), or black cohosh (Cimicifuga racemosa) and ginkgo (Ginkgo biloba). Homeopathic
remedies that may be prescribed include aconite
(Acontium napellus), Ferrum phosphoricum, belladonna, chamomile, Lycopodium, pulsatilla (Pulsatilla
nigricans), or silica. Craniosacral therapy uses gentle
manipulation of the bones of the skull to relieve pressure and improve eustachian tube function.

Prognosis
With treatment, the prognosis for acute otitis
media is very good. However, long-lasting accumulations of fluid within the middle ear are a risk
both for difficulties with hearing and speech, and
for the repeated development of ear infections.
Furthermore, without treatment, otitis media can
lead to an infection within the nearby mastoid bone,
called mastoiditis.

Prevention
Although otitis media seems somewhat inevitable in childhood, some measures can be taken to
decrease the chance of repeated infections and fluid
accumulation. Breastfeeding provides some protection against URIs, which in turn protects against
the development of otitis media. If a child is bottleGALE ENCYCLOPEDIA OF MEDICINE

fed, parents should be advised to feed him or her
upright, rather than allowing the baby to lie down
with the bottle. General good hygiene practices (especially handwashing) help to decrease the number of
upper respiratory infections in a household or daycare center.
The use of pacifiers should be avoided or limited.
They may act as fomites, particularly in a daycare
setting. In children who are more susceptible to otitis
media, pacifier use can increase by as much as 50% the
number of ear infections experienced.
Two vaccines can prevent otitis media associated
with certain strains of bacteria. One is designed to
prevent meningitis and other diseases, including otitis
media, that result from infection with Haemophilus
influenzae type B. Another is a vaccine against
Streptococcus pneumoniae, a very common cause of
otitis media. Children who are at high risk or have
had severe or chronic infections may be good candidates for these vaccines; in fact, a recent consensus
report among pediatricians recommended routine
administration of the pneumococcal conjugate vaccine to children younger than two years, as well as
those at high risk for AOM. Parents should consult a
health care provider concerning the advisability of this
treatment.
Another vaccine that appears to lower the risk
of AOM in children is the intranasal vaccine that
was recently introduced for preventing influenza.
Although the flu vaccine was not developed to prevent
AOM directly, one team of researchers found that
children who were given the vaccine before the start
of flu season were 43% less likely to develop AOM
than children who were not vaccinated.
As of early 2003, there is no vaccine effective
against M. catarrhalis. Researchers are working on
developing such a vaccine, as well as a tribacterial
vaccine that would be effective against all three pathogens that commonly cause otitis media.
A nutrition-based approach to preventive treatment is undergoing clinical trials as of late 2002. This
treatment involves giving children a dietary supplement of lemon-flavored cod liver oil plus a multivitamin formula containing selenium. The pilot study
found that children receiving the supplement had
fewer cases of otitis media, and that those who did
develop it recovered with a shorter course of antibiotic
treatment than children who were not receiving the
supplement.
After a child has completed treatment for otitis
media, a return visit to the practitioner should
be scheduled. This visit should occur after the
2725

Otitis media

In 2002 a new minimally invasive procedure was introduced that uses a laser to perform the myringotomy.
It can be performed in the doctor’s office and heals
more rapidly than the standard myringotomy.

Otitis media

Resources

Cripps, A. W., and J. Kyd. ‘‘Bacterial Otitis Media: Current
Vaccine Development Strategies.’’ Immunology and Cell
Biology 81 (February 2003): 46–51.
Decherd, M. E., R. W. Deskin, J. L. Rowen, and M. B.
Brindley. ‘‘Bordetella pertussis Causing Otitis Media:
A Case Report.’’ Laryngoscope 113 (February 2003):
226–227.
Goodwin, J. H., and J. C. Post. ‘‘The Genetics of Otitis
Media.’’ Current Allergy and Asthma Reports 2 (July
2002): 304-308.
Hoberman, A., C. D. Marchant, S. L. Kaplan, and S.
Feldman. ‘‘Treatment of Acute Otitis Media Consensus
Recommendations.’’ Clinical Pediatrics 41 (JulyAugust 2002): 373-390.
Linday, L. A., J. N. Dolitsky, R. D. Shindledecker, and
C. E. Pippinger. ‘‘Lemon-Flavored Cod Liver Oil
and a Multivitamin-Mineral Supplement for the
Secondary Prevention of Otitis Media in Young
Children: Pilot Research.’’ Annals of Otology,
Rhinology, and Laryngology 111 (July 2002):
642-652.
Marchisio, P., R. Cavagna, B. Maspes, et al. ‘‘Efficacy of
Intranasal Virosomal Influenza Vaccine in the
Prevention of Recurrent Acute Otitis Media in
Children.’’ Clinical Infectious Diseases 35 (July 15,
2002): 168-174.
Mattila, P. S., V. P. Joki-Erkkila, T. Kilpi, et al. ‘‘Prevention
of Otitis Media by Adenoidectomy in Children
Younger Than 2 Years.’’ Archives of Otolaryngology—
Head and Neck Surgery 129 (February 2003):
163–168.
Menger, D. J., and R. G. van den Berg. ‘‘Pneumocystis
carinii Infection of the Middle Ear and External
Auditory Canal. Report of a Case and Review of
the Literature.’’ ORL 65 (January-February 2003):
49–51.
Redaelli de Zinis, L. O., P. Gamba, and C. Balzanelli.
‘‘Acute Otitis Media and Facial Nerve Paralysis in
Adults.’’ Otology and Neurotology 24 (January 2003):
113–117.
Weiner, R., and P. J. Collison. ‘‘Middle Ear Pathogens in
Otitis-Prone Children.’’ South Dakota Journal of
Medicine 56 (March 2003): 103–107.

BOOKS

ORGANIZATIONS

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I: Chiropractic and Osteopathy. New York: Simon
& Schuster, 2002.

American Academy of Otolaryngology, Head and Neck
Surgery, Inc. One Prince Street, Alexandria, VA
22314-3357. (703) 836-4444.
American Academy of Pediatrics (AAP). 141 Northwest
Point Boulevard, Elk Grove Village, IL 60007. (847)
434-4000. <www.aap.org>.
American Osteopathic Association (AOA). 142 East
Ontario Street, Chicago, IL 60611. (800) 621- 1773.
<www.aoa-net.org>.

KEY TERMS
Adenoid—A collection of lymph tissue located in
the nasopharynx.
Effusion—A collection of fluid which has leaked
out into some body cavity or tissue.
Eustachian tube—A small tube which runs between
the middle ear space and the nasopharynx.
Fomite—An inanimate object that can transmit
infectious organisms.
Myringotomy—A surgical procedure performed
to drain an infected middle ear. A newer type of
myringotomy uses a laser instead of a scalpel.
Nasopharynx—The part of the airway into which
the nose leads.
Ossicles—Tiny bones located within the middle
ear which are responsible for conveying the vibrations of sound through to the inner ear.
Perforation—A hole.
Topical—Referring to a medication applied to the
skin or outward surface of the body. Ear drops are
one type of topical medication.

antibiotic has been completed, and allows the practitioner to evaluate the patient for the persistent
presence of fluid within the middle ear. In children
who have a problem with recurrent otitis media, a
small daily dose of an antibiotic may prevent repeated
full attacks of otitis media. In children who have
persistent fluid, a procedure to place tiny tubes within
the eardrum may help equalize pressure between the
middle ear and the outside, thus preventing further
fluid accumulation.

PERIODICALS

Abes, G., N. Espallardo, M. Tong, et al. ‘‘A Systematic
Review of the Effectiveness of Ofloxacin Otic Solution
for the Treatment of Suppurative Otitis Media.’’ ORL
65 (March-April 2003): 106–116.
Bucknam, J. A., and P. C. Weber. ‘‘Laser Assisted
Myringotomy for Otitis Media with Effusion in
Children.’’ ORL-Head and Neck Nursing 20 (Summer
2002): 11-13.
2726

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Otosclerosis is an excessive growth in the bones of
the middle ear which interferes with the transmission
of sound.

Description
The middle ear consists of the eardrum and a
chamber which contains three bones called the hammer, the anvil, and the stirrup (or stapes). Sound
waves passing through the ear cause the ear drum to
vibrate. This vibration is transmitted to the inner ear
by the three bones. In the inner ear, the vibrations are
changed into impulses which are carried by the nerves,
to the brain. If excessive bone growth interferes with
the stapes ability to vibrate and transmit sound waves,
hearing loss will result.
Otosclerosis is classified as a conductive disorder
because it involves the bones of the ear, which conduct
the sound to the nerve. If a person has hearing loss
classified as neural, the nerve conducting the impulses
to the brain is involved.
Otosclerosis is a common hereditary condition.
About 10% of the caucasion population has some
form of otosclerosis, however, it is rare among other
ethnic backgrounds. Women are more likely than men
to suffer from otosclerosis. It is the most common
cause of conductive hearing loss between the ages of
15–50, but if the bony growth affects only the hammer
or anvil, there are no symptoms and the condition goes
undetected. Disease affecting the stapes is also associated with progressive hearing loss.

Tinnitus—Tinnitus is noise originating in the ear,
not in the environment. The noise can range from
faint ringing to roaring.

Treatment
People with otosclerosis often benefit from a
properly fitted hearing aid.
The surgical replacement of the stapes has become
a common procedure to improve conductive hearing
problems. During this operation, called a stapedectomy,
the stapes is removed and replaced with an artificial
device. The operation is performed under local
anesthesia and is usually an outpatient procedure.
Surgery is done on only one ear at a time, with a one
year wait between procedures. The degree of hearing
improvement reaches its maximum about four months
after the surgery. Over 80% of these procedures successfully improve or restore hearing.

Prognosis
People with otosclerosis almost never become
totally deaf, and will usually be able to hear with a
hearing aid or with surgery plus a hearing aid. In older
people, the tendency for additional hearing loss is
diminished due to the hardening of the bones.

Prevention
Otosclerosis cannot be prevented.
Resources

Causes and symptoms
Otosclerosis is hereditary. Acquired illness and
accidents have no relationship to its development.
The primary symptom of otosclerosis is loss of
hearing. In addition, many people experience tinnitus
(noice originating inside the ear). The amount of
tinnitus is not necessarily related to the kind or severity of hearing loss.

Diagnosis
Hearing loss due to otosclerosis is usually first
noticed in the late teens or early twenties. Hearing
loss usually occurs in the low frequencies first,
followed by high frequencies, then middle frequencies.
Extensive hearing tests will confirm the diagnosis.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Tinnitus Association. P.O. Box 5, Portland, OR
97207. (503) 248-9985. <tinnitus@ata.org>.
National Association of the Deaf. 814 Thayer Ave., Silver
Spring, MD, 20910. (301) 587-1788. <http://
nad.policy.net>.
NIDCD Hereditary Hearing Impairment Resource
Registry. c/o Boys Town National Research Hospital.
555 N. 30th St., Omaha NE 68131. (800) 320-1171.
Self Help for Hard of Hearing People, Inc. 7800 Wisconsin
Ave., Bethesda, MD 20814. (301) 657-2248.
<http://www.shhh.org>.

Dorothy Elinor Stonely

Otoscopic examination see Ear exam with an
otoscope
2727

Otosclerosis

KEY TERMS

Otosclerosis

Ototoxicity

Ototoxicity



netilmycin (Netromycin)



vancomycin (Vancocin)

Definition
Ototoxicity is damage to the hearing or balance
functions of the ear by drugs or chemicals.

Description
Ototoxicity is drug or chemical damage to the
inner ear. This section of the ear contains both the
hearing mechanism and the vestibulocochlear nerve,
the nerve that sends hearing and balance information
to the brain. Because of this, ototoxic drugs may cause
lack of hearing, and loss of sense of balance.
The extent of ototoxicity varies with the drug, the
dose, and other conditions. In some cases, there is full
recovery after the drug has been discontinued. In other
cases, the extent of damage is limited, and may even
be too small to be noticed. This may occur in highfrequency hearing loss, where the damage to the ear
makes it difficult to hear high pitched musical notes,
but does not affect the ability to hear the spoken word,
or carry on a conversation. In extreme cases, there
may be permanent and complete deafness.
Although ototoxicity is undesirable, the ear
damage can actually be used to help people with
Ménière’s disease. This is a disease of no known
cause that is marked by sudden episodes of dizziness
and vertigo. Other symptoms include a feeling of
‘‘fullness’’ in the ears, roaring in the ears, and ringing
in the ears. While most people with this condition can
be controlled with medication, about 10% require
surgery. However, use of some ototoxic drugs can
actually improve this condition, while causing less
damage to the hearing mechanism than traditional
treatments.

Causes and symptoms
Many drugs can cause ototoxicity.
Antibiotics


amikacin (Amikin)



streptomycin



neomycin



gentamicin (Garamycin)



erythromycin (E-Mycin, Eryc)



kanamycin (Kantrex)



tobramycin (Nebcin)

2728

Anti-cancer drugs


cisplatin (Platinol AQ)



bleomycin (Blenoxane)



vincristine (Oncovin)
Diuretics



acetazolamide (Diamox)



furosemide (Lasix)



bumetanide (Bumex)



ethacrynic acid (Edecrine)

A number of other drugs and chemicals may also
cause ototoxicity. Aspirin overdose causes ringing
in the ears. The antimalarial drugs quinine and chloroquine may also cause ear damage. Among the environmental chemicals that can cause ear damage are
tin, lead, mercury, carbon monoxide, and carbon
disulfide. This list is not complete, and many other
drugs and chemicals, such as industrial solvents, may
cause ear problems.

Diagnosis
Ototoxicity often goes undiagnosed. This occurs
when the hearing loss is slight, or when it is restricted
to the higher frequencies. Patients may notice a change
in their hearing, but it may not be significant enough
to report.
In other cases, the loss of hearing may be very
significant, or the ototoxicity may take the form of
ringing in the ears, or other sensations.
When physicians are administering medications
that are known to cause hearing loss, it is often recommended that the patient receive regular hearing tests.
By monitoring hearing on a regular basis, it may be
possible to discontinue the medication, or reduce the
dose so that no further damage is done.
Ototoxicity that causes loss of balance may be
even more difficult to diagnose. These changes may
take place gradually, over time, and may be confused
with the effects of the condition the drugs are meant
to treat. If ototoxicity is suspected, balance tests
are available, including a platform balance test, and
a rotary chair. These, and other tests, determine how
a patient responds to motion and changes in body
position.
GALE ENCYCLOPEDIA OF MEDICINE

There are no current treatments to reverse the
effects of ototoxicity.
People who suffer permanent hearing loss may
elect to use hearing aids, or, when appropriate, receive
a cochlear implant. For those who have balance problems, physical therapy may often be helpful. Physical
therapists can help people with balance problems learn
to rely more on vision and the sensations from muscles
to achieve balance.

Prognosis
The prognosis depends on the drugs that caused
the ototoxicity, and their dose.
The aminoglycoside antibiotics, gentamicin, kanamycin, netilmycin and tobramycin all cause hearing loss
to varying degrees. These drugs may be used to treat lifethreatening infections that are resistant to other classes
of drugs, and so there may be no choice but to use them.
Careful dosing can minimize, but not eliminate the risk.
It is estimated that the chances of recovery are 10-15%.
The hearing loss usually begins at the higher frequencies, and is usually not recognized immediately.
Erythromycin may cause hearing loss that affects
all frequencies. This hearing loss usually reverses itself
over time.
Aspirin and the non-steroidal anti-inflammatory
drugs (NSAIDS) may cause ringing in the ears (tinnitus). This stops when the drug is discontinued.
The diuretics may cause a hearing loss with a rapid
onset. This will usually, but not always, reverse itself
when the drugs are stopped.
In some cases, the prognosis is not really clear.
Vancomycin appears to cause hearing loss, but this
may only occur when vancomycin is used at the same
time as other ototoxic drugs, such as gentamicin or
erythromycin.

Prevention
Since most ototoxicity occurs when the harmful
drugs are used in high doses, careful dose calculations
are the best method of prevention. Sometimes it is
possible to replace the ototoxic drugs with drugs that
have less severe adverse effects.
Resources
BOOKS

Ototoxicity: Basic Science and Clinical Application.
New York: New York Academy of Sciences, June 1999.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Antibiotic—Drugs that kill or inhibit the growth of
bacteria.
Cochlea—A division of the inner ear.
Diuretic—A drug that increases water loss through
increased urination.
Ménière’s disease—A disorder of the membranous
labyrinth of the inner ear that is marked by recurrent attacks of dizziness, tinnitus, and deafness—
also called Ménière’s syndrome. It is named after
Prosper Ménière (1799–1862), a French physician
who was among the first people to study diseases of
the ear, nose, and throat.
Tinnitus—Ringing sounds in the ears.

ORGANIZATIONS

Deafness Research Foundation. 1225 I St. NW, No. 500,
Washington, DC 20005.
Ear Research Foundation. 1901 Floyd St., Sarasota, FL
34239-2909.
National Institute on Deafness and Other Communication
Disorders. NIH Bldg. 10, Rm. 5C-306 9000, Rockville
Park, Bethesda, MD 20892.

Samuel D. Uretsky, PharmD

Ova & parasites collection see Stool O &
P test

Ovarian cancer
Definition
Ovarian cancer is cancer of the ovaries, the eggreleasing and hormone-producing organs of the
female reproductive tract. Cancerous, or malignant,
cells divide and multiply in an abnormal fashion.

Description
The ovaries are small, almond-shaped organs,
located in the pelvic region, one on either side of the
uterus. When a woman is in her childbearing years, the
ovaries alternate to produce and release an egg each
month during the menstrual cycle. The released egg is
picked up by the adjacent fallopian tube, and continues down toward the uterus. The ovaries also
2729

Ovarian cancer

Treatment

Ovarian cancer

produce and secrete the female hormones estrogen and
progesterone, which regulate the menstrual cycle and
pregnancy, as well as support the development of the
secondary female sexual characteristics (breasts, body
shape, and body hair). During pregnancy and when
women take certain medications, such as oral contraceptives, the ovaries are given a rest from their usual
monthly duties.
Types of ovarian cancers
Ninety percent of all ovarian cancers develop in
the cells lining the surface, or epithelium, of the ovaries
and so are called epithelial cell tumors. About 15% of
epithelial cancers are considered low malignant potential or LMP tumors. These tumors occur more often in
younger women, and are more likely to be caught
early, so prognosis is good.
Germ cell tumors develop in the egg-producing
cells of the ovary, and comprise about 5% of ovarian
tumors. These tumors are usually found in teenage
girls or young women. The prognosis is good if
found early, but as with other ovarian cancers, early
detection is difficult.
Primary peritoneal carcinoma (PPC) is a cancer of
the peritoneum, the lining of the abdominal cavity
where the internal organs are located. Although it is
a distinct disease, it is linked with ovarian cancer. This
is because the ovarian and peritoneal cells have the
same embryonic origin. This means that the very early
cells of the embryo that will ultimately develop into the
ovaries and the peritoneum share a common origin.
The term ‘‘primary’’ means that the cancer started first
in the peritoneum, as opposed to the cancer starting in
the ovary and then moving, or metastasizing, into the
peritoneum.
Ovarian cancer can develop at any age, but is most
likely to occur in women who are 50 years or older.
More than half the cases are among women who are
aged 65 years and older. Industrialized countries
have the highest incidence of ovarian cancer. Native
American and Caucasian women, especially
Caucasians of Ashkenazi Jewish descent, are at somewhat higher risk; Hispanic, African-American, and
Asian women are at a slightly lower risk. The risk of
developing the disease increases with age. Ovarian
cancer is the fifth most common cancer among
women in the United States, and the second most
common gynecologic cancer. It accounts for 4% of
all cancers in women. However, because of poor early
detection, the death rate for ovarian cancer is higher
than for that of any other cancer among women.
About 1 in 70 women in the United States will
2730

eventually develop ovarian cancer, and 1 in 100 will
die from it. The American Cancer Society estimates
that 26,000 new cases of ovarian cancer will be diagnosed in the United States in 2004, and that 16,000
women will die from the disease.
Only 50% of the women who are diagnosed with
ovarian cancer will survive five years after initial diagnosis. This is due to the cancer being at an advanced
stage at the time of diagnosis. With early detection,
however, survival at five years post diagnosis may
be 95%.

Causes and symptoms
Causes
The actual cause of ovarian cancer remains
unknown, but several factors are known to increase
one’s chances of developing the disease. These are
called risk factors. Women at a higher risk than average of developing ovarian cancer include women who:


have never been pregnant or had children,



are Caucasian, especially of Northern European or
Ashkenazi Jewish descent,



are over 50 (half of all diagnosed cases are in women
over 65),



have a family history of breast, ovarian, endometrial
(uterine), prostate, or colon cancer,



have had breast cancer,



have a first-degree relative (mother, daughter, sister)
who has had ovarian cancer. (The risk is greater if two
or more first-degree relatives had the disease. Having
a grandmother, aunt or cousin with ovarian cancer
also puts a woman at higher-than-average risk.)



have the genetic mutation BRCA1 or BRCA2. (Not
all women with these genetic breast cancer mutations
will develop ovarian cancer. By age 70, a woman who
has the BRCA1 mutation carries about a 40–60% risk
of developing ovarian cancer. Women with the genetic
mutation BRCA2 have a 15% increased risk of developing ovarian cancer. However, heredity only plays
a role in about 5–10% of cases of ovarian cancer.)

Women who have a strong familial history may
benefit from genetic counseling to better understand
their risk factors.
In addition to the above risk factors, the following
factors appear to play a role in affecting a women’s
chances of developing ovarian cancer.
Reproduction and hormones. Early menstruation
(before age 12) and late menopause seem to put women
at a higher risk for ovarian cancer. This appears to be
GALE ENCYCLOPEDIA OF MEDICINE

Infertility drug-stimulated ovulation. Research
studies have reported mixed findings on this issue. It
appears that women who take medications to stimulate ovulation, yet do not become pregnant, are at
higher risk of developing ovarian cancer. Women
who do become pregnant after taking fertility drugs
do not appear to be at higher risk. One study reported
that the use of the fertility drug clomiphene citrate for
more than a year increased the risk of developing LMP
tumors. LMP tumors respond better to treatment than
other ovarian tumors.
Talc. The use of talcum powder in the genital area
has been implicated in ovarian cancer in many studies.
It may be because talc contains particles of asbestos,
a known carcinogen. Female workers exposed to
asbestos had a higher-than-normal risk of developing
ovarian cancer. Genital deodorant sprays may also
present an increased risk. Not all studies have brought
consistent results.
Fat. A high-fat diet has been reported in some
studies to increase the risk of developing ovarian
cancer. In one study the risk level increased with every
10 grams of saturated fat added to the diet. This may
be because of its effect on estrogen production.

as being ovarian in nature only after a significant
length of time had passed.
The following symptoms are warning signs of
ovarian cancer, but could also be due to other causes.
Symptoms that persist for two to three weeks, or
symptoms that are unusual for the particular woman
should be evaluated by a doctor right away.


digestive symptoms, such as gas, indigestion, constipation, or a feeling of fullness after a light meal



bloating, distention or cramping



abdominal or low-back discomfort



pelvic pressure or frequent urination



unexplained changes in bowel habits



nausea or vomiting



pain or swelling in the abdomen



loss of appetite



fatigue



unexplained weight gain or loss



pain during intercourse



vaginal bleeding in post-menopausal women

Diagnosis
In the best-case scenario a woman is diagnosed
with ovarian cancer while it is still contained in just
one ovary. Early detection can bring five-year survival
to near 95%. Unfortunately, about 75% of women
(3 out of 4) have advanced ovarian cancer at the time
of diagnosis. (Advanced cancer is at stage III or stage
IV when it has already spread to other organs.) Fiveyear survival for women with stage IV ovarian cancer
may be less than 5%.
Diagnostic tests and techniques

Symptoms
Most of the literature on ovarian cancer states
that there are usually no early warning symptoms for
the disease. Ovarian cancer is often referred to as a
silent killer, because women either are unaware of
having it, or have symptoms that are not accurately
diagnosed until the disease is in an advanced state.
However, a November 2000 study reported in the
medical journal Cancer analyzed more than 1,700
questionnaires completed by women with stage III
and stage IV ovarian cancer. The researchers found
that 95% of the women reported having had early
symptoms that they brought to their doctors. Most
symptoms were somewhat vague and either abdominal or gastrointestinal in nature, and consequently
were either not properly diagnosed or were recognized
GALE ENCYCLOPEDIA OF MEDICINE

If ovarian cancer is suspected, several of the following tests and examinations will be necessary to
make a diagnosis:


a complete medical history to assess all the risk
factors



a thorough bi-manual pelvic examination



CA-125 assay



one or more various imaging procedures



a lower GI series, or barium enema



diagnostic laparoscopy

BI-MANUAL PELVIC EXAMINATION. The exam
should include feeling the following organs for any
abnormalities in shape or size: the ovaries, fallopian

2731

Ovarian cancer

because the longer, or more often, a woman ovulates,
the higher her risk for ovarian cancer. As mentioned
above, women who were never pregnant have a higher
risk of developing the disease than women with one or
more pregnancies. It is not yet clear from research
studies whether a pregnancy that ends in miscarriage
or stillbirth lowers the risk factor to the same degree
as the number of term pregnancies. The use of postmenopausal estrogen supplementation for 10 years or
more may double a woman’s risk of ovarian cancer.
Short-term use does not seem to alter one’s risk factor.

Ovarian cancer

tubes, uterus, vagina, bladder, and rectum. Because
the ovaries are located deep within the pelvic area, it is
unlikely that a manual exam will pick up an abnormality while the cancer is still localized. However, a
full examination provides the practitioner with a more
complete picture. An enlarged ovary does not confirm
cancer, as the ovary may be large because of a cyst or
endometriosis. While women should have an annual
Pap test, this test screens for cervical cancer.
Cancerous ovarian cells, however, might be detected
on the slide. Effectiveness of using Pap smears for
ovarian cancer detection is about 10-30%.
CA-125 ASSAY. This is a blood test to determine the
level of CA-125, a tumor marker. A tumor marker is a
measurable protein-based substance given off by the
tumor. A series of CA-125 tests may be done to see if
the amount of the marker in the blood is staying
stable, increasing or decreasing. A rising CA-125
level usually indicates cancer, while a stable or declining value is more characteristic of a cyst. The CA-125
level should never be used alone to diagnose ovarian
cancer. It is elevated in about 80% of women with
ovarian cancer, but in 20% of cases is not. In addition,
it could be elevated because of a non-ovarian cancer,
or it can be elevated with non-malignant gynecologic
conditions, such as endometriosis or ectopic pregnancy. During menstruation the CA-125 level may be
elevated, so the test is best done when the woman is not
in her menses.
IMAGING. There are several different imaging
techniques used in ovarian cancer evaluation. A
fluid-filled structure such as a cyst creates a different
image than does a solid structure, such as a tumor.
An ultrasound uses high-frequency sound waves that
create a visual pattern of echoes of the structures at
which they are aimed. It is painless, and is the same
technique used to check the developing fetus in the
womb. Ultrasound may be done externally through
the abdomen and lower pelvic area, or with a transvaginal probe.

Other painless imaging techniques are computed
tomography (CT) and magnetic resonance imaging
(MRI). Color Doppler analysis provides additional
contrast and accuracy in distinguishing masses.
It remains unclear whether Doppler is effective in
reducing the high number of false-positives with transvaginal ultrasonography. These imaging techniques
allow better visualization of the internal organs and
can detect abnormalities without having to perform
surgery.
LOWER GI SERIES. A lower GI series, or barium
enema, uses a series of x rays to highlight the colon

2732

and rectum. To provide contrast, the patient drinks a
chalky liquid containing barium. This test might be
done to see if the cancer had spread to these areas.
DIAGNOSTIC LAPAROSCOPY. This technique uses a
thin hollow lighted instrument inserted through a
small incision in the skin near the belly button to
visualize the organs inside of the abdominal cavity.
If the ovary is believed to be malignant, the entire
ovary is removed (oophorectomy) and its tissue sent
for evaluation to the pathologist, even though only a
small piece of the tissue is needed for evaluation.
If cancer is present, great care must be taken not to
cause the rupture of the malignant tumor, as this
would cause spreading of the cancer to adjacent
organs. If the cancer is completely contained in the
ovary, its removal functions also as the treatment.
If the cancer has spread or is suspected to have spread,
then a saline solution may be instilled into the cavity
and then drawn out again. This technique is called
peritoneal lavage. The aspirated fluid will be evaluated
for the presence of cancer cells. If peritoneal fluid is
present, called ascites, a sample of this will also be
drawn and examined for malignant cells. If cancer
cells are present in the peritoneum, then treatment
will be directed at the abdominal cavity as well.
RESEARCH AND NEW DIAGNOSTIC TESTS. Many
cancer researchers recognize the urgency of developing a new diagnostic test for ovarian cancer that is
both sensitive and reliable. Some experts in the field
look to proteomics, which is the large-scale identification and analysis of all the proteins in an organism
or organ, to lead eventually to the development of a
useful new test for ovarian cancer.

A group of researchers in Canada reported in
2003 that human kallikrein gene 14 (KLK14) might
serve as a new biomarker for ovarian cancer.
Kallikreins are a group of compounds that help to
split up complex protein molecules into smaller units;
prostate-specific antigen, or PSA, is a kallikrein. Early
results of tests for KLK14 indicate that about 65% of
women known to have ovarian cancer have elevated
levels of this kallikrein.

Treatment
Clinical staging
Staging is the term used to determine if the cancer
is localized or has spread, and if so, how far and to
where. Staging helps define the cancer, and will determine the course of suggested treatment. Staging
involves examining any tissue samples that have been
taken from the ovary, nearby lymph nodes, as well as
GALE ENCYCLOPEDIA OF MEDICINE

Ovarian cancer

A stage I tumor of the ovary. (Illustration by Argosy Inc.)

from any nearby organs or structures where metastasis
was suspected. This may include the diaphragm, lungs,
stomach, intestines and omentum (the tissue covering
internal organs), and any fluid as described above.
The National Cancer Institute Stages for ovarian
cancer are:


Stage I: Cancer is confined to one or both ovaries.



Stage II: Cancer is found in one or both ovaries and/
or has spread to the uterus, fallopian tubes, and/or
other body parts within the pelvic cavity.



Stage III: Cancer is found in one or both ovaries and
has spread to lymph nodes or other body parts within
the abdominal cavity, such as the surfaces of the liver
or intestines.



Stage IV: Cancer is found in one or both ovaries and
has spread to other organs such as the liver or lung.

The individual stages are also further broken
down in detail, such as Ia, Ib, etc. Accurate staging is
important for several reasons. Treatment plans are
based on staging, in part because of trying to duplicate
the best results achieved in prior research trials. When
staging is inconsistent, it becomes more difficult to
know how different research studies compare, so the
results themselves cannot be relied upon.
Treatment offered will primarily depend on the
stage of the cancer and the woman’s age. It is always
appropriate to consider getting a second opinion,
especially when treatment involves surgery, chemotherapy, and possible radiation. Before the patient
GALE ENCYCLOPEDIA OF MEDICINE

makes her decision as to which course of treatment to
take, she should feel that she has the information
necessary with which to make an informed decision.
The diagnostic tools mentioned above are used to
determine the course of treatment. However, the treatment plan may need to be revised if the surgeon sees
that the tumor has spread beyond the scope of what
was seen during diagnostic tests.
Surgery
Surgery is done to remove as much of the tumor as
possible (called tissue debulking), utilizing chemotherapy and/or radiation to target cancer cells that have
remained in the body, without jeopardizing the
woman’s health. This can be hard to balance once
the cancer has spread. Removal of the ovary is called
oophorectomy, and removal of both ovaries is called
bilateral oophorectomy. Unless it is very clear that the
cancer has not spread, the fallopian tubes are usually
removed as well (salpingo-oophorectomy). Removal of
the uterus is called hysterectomy.
If the woman is very young, all attempts will be
made to spare the uterus. It is crucial that a woman
discuss with her surgeon her childbearing plans prior
to surgery. Unfortunately, ovarian cancer spreads
easily and often swiftly throughout the reproductive
tract. It may be necessary to remove all reproductive
organs as well as part of the lining of the peritoneum to
provide the woman with the best possible chance of
long-term survival. Fertility-sparing surgery can be
successful if the ovarian cancer is caught very early.
2733

Ovarian cancer

Side effects of the surgery will depend on the
extent of the surgery, but may include pain and temporary difficulty with bladder and bowel function, as
well as reaction to the loss of hormones produced by
the organs removed. A hormone replacement patch
may be applied to the woman’s skin in the recovery
room to help with the transition. An emotional side
effect may be the feeling of loss stemming from the
removal of reproductive organs.
Chemotherapy
Chemotherapy is used to target cells that have
traveled to other organs, and throughout the body
via the lymphatic system or the blood stream.
Chemotherapy drugs are designed to kill cancer cells,
but may also be harmful to healthy cells as well.
Chemotherapy may be administered through a vein
in the arm (intravenous, IV), may be taken in tablet
form, and/or may be given through a thin tube called a
catheter directly into the abdominal cavity (intraperitoneal). IV and oral chemotherapy drugs travel
throughout the body; intraperitoneal chemotherapy
is localized in the abdominal cavity.
Side effects of chemotherapy can vary greatly
depending on the drugs used. Currently, chemotherapy drugs are often used in combinations to treat
advanced ovarian cancer, and usually the combination
includes a platinum-based drug (such as cisplatin) with
a taxol agent, such as paclitaxel. Some of the combinations used or being studied include: carboplatin/
paclitaxel, cisplatin/paclitaxel, cisplatin/topotecan,
and cisplatin/carboplatin. As new drugs are evaluated
and developed, the goal is always for maximum effectiveness with minimum side effects. Side effects include
nausea and vomiting, diarrhea, decreased appetite
and resulting weight loss, fatigue, headaches, loss of
hair, and numbness and tingling in the hands or feet.
Managing these side effects is an important part of
cancer treatment.
After the full course of chemotherapy has been
given, the surgeon may perform a ‘‘second look’’ surgery to examine the abdominal cavity again to evaluate the success of treatment.
Radiation
Radiation uses high-energy, highly focused x rays
to target very specific areas of cancer. This is done
using a machine that generates an external beam.
Very careful measurements are taken so that the
targeted area can be as focused and small as possible.
Another form of radiation uses a radioactive liquid
that is administered into the abdominal cavity in the
2734

same fashion as intraperitoneal chemotherapy.
Radiation is usually given on a daily Monday though
Friday schedule and for several weeks continuously.
Radiation is not painful, but side effects can include
skin damage at the area exposed to the external beam,
and extreme fatigue. The fatigue may hit suddenly in
the third week or so of treatment, and may take a while
to recover even after treatments have terminated.
Other side effects may include nausea, vomiting, diarrhea, loss of appetite, weight loss and urinary difficulties. For patients with incurable ovarian cancer,
radiation may be used to shrink tumor masses to
provide pain relief and improve quality of life.
Once the full course of treatment has been undertaken, it is important to have regular follow-up care to
monitor for any long-term side effects as well as for
future relapse or metastases.

Alternative treatment
The term alternative therapy refers to therapy
utilized instead of conventional treatment. By definition, these treatments have not been scientifically proven or investigated as thoroughly and by the same
standards as conventional treatments. The terms complementary or integrative therapies denote practices
used in conjunction with conventional treatment.
Regardless of the therapies chosen, it is key for
patients to inform their doctors of any alternative or
complementary therapies being used or considered.
(Some alternative and complementary therapies
adversely affect the effectiveness of conventional treatments.) Some common complementary and alternative medicine techniques and therapies include:


prayer and faith healing



meditation



mind/body techniques such as support groups, visualization, guided imagery and hypnosis



energy work such as therapeutic touch and Reiki



Acupuncture and Chinese herbal medicine



body work such as yoga, massage and t’ai chi



vitamins and herbal supplements



diets such as vegetarianism and macrobiotic

Mind/body techniques along with meditation,
prayer, yoga, T’ai Chi and acupuncture have been
shown to reduce stress levels, and the relaxation provided may help boost the body’s immune system. The
effectiveness of other complementary and alternative
treatments is being studied by the National Institutes
of Health’s National Center for Complementary and
GALE ENCYCLOPEDIA OF MEDICINE

Some programs for treatment of ovarian cancer
integrate alternative or complementary treatments
with conventional surgery or chemotherapy. As of
early 2003, the University of Kansas Medical Center
is conducting a study of the effectiveness of adding
four well-known antioxidants (vitamins A, C, E, and
beta-carotene) to standard chemotherapy regimens
for ovarian cancer.
Prognosis
Prognosis for ovarian cancer depends greatly
on the stage at which it is first diagnosed. While
stage I cancer may have a 95% success rate, stages
III and IV may have a survival rate of 17-30% at five
years post-diagnosis. Early detection remains an elusive, yet hopeful, goal of research. Also, clinical trials
are addressing new drug and treatment combinations
to prolong survival in women with more advanced
disease. Learning one’s family history may assist in
early detection, and genetic studies may clarify who is
at greater risk for the disease.
Research studies are usually designed to compare
a new treatment method against the standard method,
or the effectiveness of a drug against a placebo (an
inert substance that would be expected to have no
effect on the outcome). Since the research is experimental in nature, there are no guarantees about the
outcome. New drugs being used may have harmful,
unknown side effects. Some people participate to help
further knowledge about their disease. For others, the
study may provide a possible treatment that is not yet
available otherwise. If one participates in a study and
is in the group receiving the standard care or the
placebo, and the treatment group gets clear benefit, it
may be possible to receive the experimental treatment
once one’s original participation role is over.
Participants will have to meet certain criteria before
being admitted into the study. It is important to fully
understand one’s role in the study, and weigh the
potential risks versus benefits when deciding whether
or not to participate.

Prevention
Since the cause of ovarian cancer is not known, it
is not possible to fully prevent the disease. However,
there are ways to reduce one’s risks of developing the
disease.

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Biomarker—A biochemical substance that can be
detected in blood samples and indicates the presence of a cancerous tumor.
Gynecologic oncologist—A physician specializing
in the treatment of cancers of the female reproductive tract.
Kallikrein—Any of a group of compounds in the
body known as serine endopeptidases that help to
break down proteins into smaller units. Prostatespecific antigen belongs to this group of chemicals.
A recently discovered kallikrein may be useful as a
biomarker for ovarian cancer.
Lymphatic system—A connected network of
nodes, or glands, that carry lymph throughout the
body. Lymph is a fluid that contains the infectionfighting white blood cells that form part of the
body’s immune system. Because the network goes
throughout the body, cancer cells that enter the
lymphatic system can travel to and be deposited
at any point into the tissues and organs and form
new tumors there.
Paclitaxel—A drug derived from the common yew
tree (Taxus baccata) that is the mainstay of chemotherapy for ovarian cancer.
Pathologist—The pathologist is a doctor specializing in determining the presence and type of disease
by looking at cells and tissue samples.

Decrease ovulation. Pregnancy gives a break from
ovulation, and multiple pregnancies appear to further
reduce the risk of ovarian cancer. The research is not
clear as to whether the pregnancy must result in a term
delivery to have full benefit. Women who breastfeed
their children also have a lower risk of developing the
disease. Since oral contraceptives suppress ovulation,
women who take birth control pills (BCPs), even for as
little as 3 to 6 months have a lower incidence of the
disease. It appears that the longer a woman takes
BCPs, the lower her risk for ovarian cancer. Also,
this benefit may last for up to 15 years after a woman
has stopped taking them. However, since BCPs alter a
woman’s hormonal status, her risk for other hormonally related cancers may change. For this reason it is
very important to discuss all the risks and benefits with
one’s health care provider.
Genetic testing. Tests are available which can help
to determine whether a woman who has a family
2735

Ovarian cancer

Alternative Medicine (NCCAM). For a current list
of the research studies occurring, results of recent
studies, or publications available, patients can visit
the NCCAM web site or call at (888) 644-6226.

Ovarian cancer

history of breast, endometrial, or ovarian cancer has
inherited the mutated BRCA gene that predisposes her
to these cancers. If the woman tests positive for the
mutation, then she may be able to choose to have her
ovaries removed. Even without testing for the mutated
gene, some women with strong family histories of
ovarian cancer may consider having their ovaries
removed as a preventative measure (prophylactic
oophorectomy). This procedure diminishes but does
not completely remove the risk of cancer, as some
women may still develop primary peritoneal carcinoma after oophorectomy.
Surgery. Procedures such as tubal ligation (in
which the fallopian tubes are blocked or cut off) and
hysterectomy (in which the uterus is removed) appear
to reduce the risk of ovarian cancer. However, any
removal of the reproductive tract organs has surgical
as well as hormonal side effects.
Screening. There are no definitive tests or screening procedures to detect ovarian cancer in its early
stages, although a blood test for early detection of
asymptomatic ovarian cancer is under development
as of early 2003. Women at high risk should consult
with their physicians about regular screenings, which
may include transvaginal ultrasound and the blood test
for the CA-125 protein.
The American Cancer Society recommends
annual pelvic examinations for all women after age
40, in order to increase the chances of early detection
of ovarian cancer.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Ovarian Cancer.’’ Section 18, Chapter 241. In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Cancer.’’ New York: Simon & Schuster, 2002.
Runowicz, Carolyn D., Jeanne A. Petrek, and Ted S.
Gansler. American Cancer Society: Women and Cancer.
New York: Villard Books/Random House, 1999.
Teeley, Peter, and Philip Bashe. The Complete Cancer
Survival Guide. New York: Doubleday, 2000.
PERIODICALS

Almadrones, L. A. ‘‘Treatment Advances in Ovarian
Cancer.’’ Cancer Nursing 26, Supplement 6 (December
2003): 16S–20S.
Ayhan, A., H. Celik, C. Taskiran, et al. ‘‘Oncologic and
Reproductive Outcome after Fertility-Saving Surgery
in Ovarian Cancer.’’ European Journal of
Gynaecological Oncology (March 2003): 223–232.
2736

Balat, O., and M. G. Ugur. ‘‘Prolonged Stabilization of
Platinum/Paclitaxel-Refractory Ovarian Cancer with
Topotecan: A Case Report and Review of the
Literature.’’ Clinical and Experimental Obstetrics and
Gynecology 30 (February 2003): 151–152.
Borgono, C. A., L. Grass, A. Soosaipillai, et al. ‘‘Human
Kallikrein 14: A New Potential Biomarker for Ovarian
and Breast Cancer.’’ Cancer Research 63 (December 15,
2003): 9032–9041.
Drisko, J. A., J. Chapman, and V. J. Hunter. ‘‘The Use of
Antioxidant Therapies During Chemotherapy.’’
Gynecologic Oncology 88 (March 2003): 434–439.
Kohn, E. C., G. B. Mills, and L. Liotta. ‘‘Promising
Directions for the Diagnosis and Management of
Gynecological Cancers.’’ International Journal of
Gynaecology and Obstetrics 83, Supplement 1 (October
2003): 203–209.
McCorkle, R., J. Pasacreta, and S. T. Tang. ‘‘The Silent
Killer: Psychological Issues in Ovarian Cancer.’’
Holistic Nursing Practice 17 (November-December
2003): 300–308.
O’Rourke, J., and S. M. Mahon. ‘‘A Comprehensive Look
at the Early Detection of Ovarian Cancer.’’ Clinical
Journal of Oncology Nursing 7 (January-February
2003): 41–47.
Ray-Coquard, I., T. Bachelot, J. P. Guastalla, et al.
‘‘Epirubicin and Paclitaxel (EPI-TAX Regimen) for
Advanced Ovarian Cancer After Failure of PlatinumContaining Regimens.’’ Gynecologic Oncology 88
(March 2003): 351–357.
See, H. T., J. J. Kavanagh, W. Hu, and R. C. Bast. ‘‘Targeted
Therapy for Epithelial Ovarian Cancer: Current Status
and Future Prospects.’’ International Journal of
Gynecological Cancer 13 (November-December 2003):
701–734.
ORGANIZATIONS

American Cancer Society. (800) ACS-2345. <http://
www.cancer.org>.
Cancer Research Institute. 681 Fifth Avenue, New York,
NY 10022. (800) 992-2623. <http://
www.cancerresearch.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(301) 435-3848. <http://www.nci.nih.gov>.
National Center for Complementary and Alternative
Medicine. NCCAM Clearinghouse, P.O. Box 8218,
Silver Spring, MD 20907-8218. (888) 644-6226.
<http://nccam.nih.gov>.
Oncolink at the University of Pennsylvania. <http://
www.oncolink.upenn.edu>.
Women’s Cancer Network. c/o Gynecologic Cancer
Foundation, 401 N. Michigan Avenue, Chicago, IL
60611. (312) 644-6610. <http://www.wcn.org>.
OTHER

Ovarian Cancer Home Page, National Cancer Institute.
<http://www.nci.nih.gov/cancer_information/
cancer_type/ovarian/>.
GALE ENCYCLOPEDIA OF MEDICINE

Esther Csapo Rastegari, R.N., B.S.N., Ed.M.
Rebecca J. Frey, PhD

Ovarian cysts
Definition
Ovarian cysts are sacs containing fluid or semisolid material that develop in or on the surface of an
ovary.

Description
Ovarian cysts are common and the vast majority
are harmless. Because they cause symptoms that may
be the same as ovarian tumors that may be cancerous,
ovarian cysts should always be checked out. The most
common types of ovarian cysts are follicular and
corpus luteum, which are related to the menstrual
cycle. Follicular cysts occur when the cyst-like follicle
on the ovary in which the egg develops does not burst
and release the egg. They are usually small and harmless, disappearing within two to three menstrual cycles.
Corpus luteum cysts occur when the corpus luteum—a
small, yellow body that secretes hormones—does not
dissolve after the egg is released. They usually disappear in a few weeks but can grow to more than
4 in (10 cm) in diameter and may twist the ovary.
Ovarian cysts can develop at any time in a
female’s life from infancy to puberty to menopause,
including during pregnancy. Follicular cysts occur
frequently during the years when a woman is menstruating, and are nonexistent in postmenopausal women
or any woman who is not ovulating. Corpus luteum
cysts occur occasionally during the menstrual years
and during early pregnancy. (Dermoid cysts, which
may contain hair, teeth, or skin derived from the
outer layer of cells of an embryo, are also occasionally
found in the ovary.)

Causes and symptoms
Causes
Follicular cysts are caused by the formation of too
much fluid around a developing egg. Corpus luteum
cysts are caused by excessive accumulation of blood
GALE ENCYCLOPEDIA OF MEDICINE

during the menstrual cycle, hormone therapy, or other
types of ovarian tumors.
There is also a condition known as polycystic
ovary syndrome (PCOS) in which the eggs and follicles are not released from the ovaries and instead
form multiple cysts. Obesity is linked to this condition, as 50% of women with PCOS are also obese.
Hormonal imbalances play a major role in this condition, including high levels of the hormone androgen
and low levels of progesterone, the female hormone
necessary for egg release. High levels of insulin, the
hormone that regulates blood sugar, are often found
in women with PCOS. PCOS is also characterized by
irregular menstrual periods, infertility, and hirsutism
(excessive hair growth on the body and face).
Although PCOS was formerly thought to be an
adult-onset condition, more recent research indicates
that it begins in childhood, possibly even during fetal
development.
PCOS is also known to run in families, which
suggests that genetic factors contribute to its development. As of 2002, the specific gene or genes responsible
for PCOS have not yet been identified; however, several groups of researchers in different countries have
been investigating genetic variations associated with
increased risk of type 2 diabetes in order to determine
whether the same genetic variations may be involved
in PCOS.
In adolescent girls, ovarian cysts may be associated with a genetic disorder known as McCuneAlbright syndrome, which is characterized by abnormal bone growth, discoloration of the skin, and early
onset of puberty. The ovarian cysts are responsible for
the early sexual maturation.
As of early 2003, McCune-Albright syndrome is
known to be associated with mutations in the GNAS1
gene. The mutation is sporadic, which means that it
occurs during the child’s development in the womb
and that the syndrome is not inherited.
Symptoms
Many ovarian cysts have no symptoms. When the
growth is large or there are multiple cysts, the patient
may experience any of the following symptoms:


Fullness or heaviness in the abdomen.



Pressure on the rectum or bladder.



Pelvic pain that is a constant dull ache and may
spread to the lower back and thighs, occurs shortly
before the beginning or end of menstruation, or
occurs during intercourse.
2737

Ovarian cysts

‘‘Ovarian Cancer.’’ OncoLink: University of Pennsylvania
Cancer Center. July 5, 2001. [cited July 6, 2001].
<http://cancer.med.upenn.edu/specialty/gyn_onc/
ovarian/>.

Ovarian cysts

Long-term management of PCOS has been complicated in the past by lack of a clear understanding of
the causes of the disorder. Most commonly, hormonal
therapy has been recommended, including estrogen
and progesterone and such other hormone-regulating
drugs as ganirelix (Antagon). Birth control pills have
also been prescribed by doctors to regulate the menstrual cycle and to shrink functional cysts.

An ovarian cyst is being surgically removed from a 25-yearold female patient. (Photograph by Art Siegel, Custom Medical
Stock Photo. Reproduced by permission.)

Diagnosis
Non-symptomatic ovarian cysts are often felt by a
doctor examining the ovaries during a routine pelvic
exam. Symptomatic ovarian cysts are diagnosed through
a pelvic exam and ultrasound. Ultrasonography is a
painless test that uses a hand-held wand to send and
receive sound waves to create images of the ovaries on
a computer screen. The images are photographed for
later analysis. It takes about 15 minutes and is usually
done in a hospital or a physician’s office.
Ovarian cysts can be diagnosed in female fetuses
by transabdominal ultrasound during the mother’s
pregnancy.

Treatment
Watchful waiting
Many follicular and corpus luteum cysts require
no treatment and disappear on their own. Often the
physician will wait and re-examine the patient in four
to six weeks before taking any action. Follicular cysts
do not require treatment, but birth control pills may
be taken if the cysts interfere with the patient’s daily
activities.
Most uncomplicated ovarian cysts in female
infants resolve on their own shortly after delivery.
Complicated cysts are treated by laparoscopy or laparotomy after the baby is born.
Medications
McCune-Albright syndrome is treated with testolactone (Teslac), an anti-estrogen drug that corrects
the hormonal imbalance caused by the ovarian cysts.
2738

More recent studies have shown that increasing
sensitivity to insulin in women with PCOS leads to
improvement in both the hormonal and metabolic
symptoms of the disorder. As of 2002, this sensitivity
is increased by either weight loss and exercise programs or by medications. Metformin (Glucophage),
a drug originally developed to treat type 2 diabetes,
has been shown to be effective in reducing the symptoms of hyperandrogenism as well as insulin resistance
in women with PCOS.
Another strategy that is being tried with PCOS
is administration of flutamide (Eulexin), a drug normally used to treat prostate cancer in men. Preliminary
results indicate that the antiandrogenic effects of flutamide benefit patients with PCOS by increasing
blood flow to the uterus and ovaries.
Surgery
Surgery is usually indicated for patients who have
not reached puberty and have an ovarian mass and
in postmenopausal patients. Surgery is also indicated
if the growth is larger than 4 in (10 cm), complex,
growing, persistent, solid and irregularly shaped, on
both ovaries, or causes pain or other symptoms.
Ovarian cysts are curable with surgery but often
recur without it.
Surgical options include removal of the cyst or
removal of one or both ovaries. More than 90% of
benign ovarian cysts can be removed using laparoscopy, a minimally invasive outpatient procedure. In
laparoscopic cystectomy, the patient receives a general
or local anesthetic, then a small incision is made in
the abdomen. The laparoscope is inserted into the
incision and the cyst or the entire ovary is removed.
Laparoscopic cystectomy enables the patient to return
to normal activities within two weeks. Surgical cystectomy to remove cysts and/or ovaries is performed
under general anesthesia in a hospital and requires a
stay of five to seven days. After an incision is made in
the abdomen, the muscles are separated and the membrane surrounding the abdominal cavity (peritoneum)
is opened. Blood vessels to the ovaries are clamped
and tied. The cyst is located and removed. The peritoneum is closed, and the abdominal muscles and skin
GALE ENCYCLOPEDIA OF MEDICINE

Ovarian cysts

Single
ovarian
cyst

Multiple
ovarian
cysts

(Illustration by Argosy Inc.)

are closed with sutures or clips. Recovery takes four
weeks.
A surgical procedure known as ovarian wedge
resection appears to improve fertility in women with
PCOS who have not responded to drug treatments. In
an ovarian wedge resection, the surgeon removes a
portion of the polycystic ovary in order to induce
ovulation.

Alternative treatment
Alternative treatments for ovarian problems—
herbal therapies, nutrition and diet, and homeopathy—should be used to supplement, not replace,
conventional treatment. General herbal tonics for
female reproductive organs that can be taken in tea
or tincture (an alcohol-based herbal extract) form
include blue cohosh (Caulophylum thalictroides)
and false unicorn root (Chamaelirium luteum).
Recommendations to help prevent and treat ovarian
cysts include a vegan diet (no dairy or animal products) that includes beets, carrots, dark-green leafy
vegetables, and lemons; anitoxidant supplements
including zinc and vitamins A, E, and C; as well as
black currant oil, borage oil, and evening primrose oil
(Oenothera biennis) supplements. Homeopathic treatments—tablets, powders, and liquids prepared from
plant, mineral, and animal extracts—may also be
GALE ENCYCLOPEDIA OF MEDICINE

effective in treating ovarian cysts. Castor oil packs
can help reduce inflammation. Hydrotherapy applied
to the abdomen can help prevent rupture of the cyst
and assist its reabsorption.

Prognosis
The prognosis for non-cancerous ovarian cysts
is excellent.

Prevention
Ovarian cysts cannot be prevented.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Pelvic Pain.’’ Section 18, Chapter 237. In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Physical Conditions in Adolescence.’’ Section 19,
Chapter 275. In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Pregnancy Complicated by Disease: Disorders
Requiring Surgery.’’ Section 18, Chapter 251. In The
2739

Ovarian torsion

KEY TERMS
Corpus luteum—A small, yellow structure that
forms in the ovary after an egg has been released.
Cystectomy—Surgical removal of a cyst.
Dermoid—A skin-like benign growth that may
appear on the ovary and resemble a cyst.
Endocrine—Internal secretions, usually in the systemic circulation.
Follicular—Relating to one of the round cells in the
ovary that contain an ovum.
Hirsutism—A condition marked by excessive hair
growth on the face and body.
Functional cyst—A benign cyst that forms on the
ovary and resolves on its own without treatment.
McCune-Albright syndrome (MCAS)—A genetic
syndrome characterized in girls by the development
of ovarian cysts and puberty before the age of 8,
together with abnormalities of bone structure and
skin pigmentation.
Ovulation—The phase of the female monthly cycle
when a developed egg is released from the ovary
into the fallopian tube for possible fertilization.
Polycystic ovarian syndrome (PCOS)—A condition
in which the eggs are not released from the ovaries
and instead form multiple cysts.

Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Ajossa, S., S. Guerriero, A. M. Paoletti, et al. ‘‘The
Antiandrogenic Effect of Flutamide Improves Uterine
Perfusion in Women with Polycystic Ovary Syndrome.’’
Fertility and Sterility 77 (June 2002): 1136–1140.
de Sanctis, C., R. Lala, P. Matarazzo, et al. ‘‘Pubertal
Development in Patients with McCune-Albright
Syndrome or Pseudohypoparathyroidism.’’ Journal of
Pediatric Endocrinology and Metabolism 16,
Supplement 2 (March 2003): 293–296.
Ehrmann, D. A., P. E. Schwarz, M. Hara, et al.
‘‘Relationship of Calpain-10 Genotype to Phenotypic
Features of Polycystic Ovary Syndrome.’’ Journal of
Clinical Endocrinology and Metabolism 87 (April 2002):
1669–1673.
Elkind-Hirsch, K. E., B. W. Webster, C. P. Brown, and
M. W. Vernon. ‘‘Concurrent Ganirelix and Follitropin
Beta Therapy is an Effective and Safe Regimen for
Ovulation Induction in Women with Polycystic Ovary
Syndrome.’’ Fertility and Sterility 79 (March 2003):
603–607.
2740

Franks, S. ‘‘Adult Polycystic Ovary Syndrome Begins in
Childhood.’’ Best Practice and Research: Clinical
Endocrinology and Metabolism 16 (June 2002): 263–272.
Kazerooni, T., and M. Dehghan-Kooshkghazi. ‘‘Effects of
Metformin Therapy on Hyperandrogenism in Women
with Polycystic Ovarian Syndrome.’’ Gynecological
Endocrinology 17 (February 2003): 51–56.
Legro, R. S. ‘‘Polycystic Ovary Syndrome. Long-Term
Sequelae and Management.’’ Minerva ginecologica 54
(April 2002): 97–114.
Marx, T. L., and A. E. Mehta. ‘‘Polycystic Ovary Syndrome:
Pathogenesis and Treatment Over the Short and Long
Term.’’ Cleveland Clinic Journal of Medicine 70
(January 2003): 31–33, 36–41, 45.
Mittermayer, C., W. Blaicher, D. Grassauer, et al. ‘‘Fetal
Ovarian Cysts: Development and Neonatal Outcome.’’
Ultraschall in der Medizin 24 (February 2003): 21–26.
Ovalle, F., and R. Azziz. ‘‘Insulin Resistance, Polycystic
Ovary Syndrome, and Type 2 Diabetes Mellitus.’’
Fertility and Sterility 77 (June 2002): 1095–1105.
Vankova, M., J. Vrbikova, M. Hill, et al. ‘‘Association of
Insulin Gene VNTR Polymorphism with Polycystic
Ovary Syndrome.’’ Annual of the New York Academy
of Sciences 967 (June 2002): 558–565.
Yildirim, M., V. Noyan, M. Bulent Tiras, et al. ‘‘Ovarian
Wedge Resection by Minilaparatomy in Infertile
Patients with Polycystic Ovarian Syndrome: A New
Technique.’’ European Journal of Obstetrics,
Gynecology, and Reproductive Biology 107 (March 26,
2003): 85–87.
ORGANIZATIONS

American College of Obstetricians and Gynecologists
(ACOG). 409 12th Street, SW, P. O. Box 96920,
Washington, DC 20090-6920. <http://
www.acog.org>.
The Health Resource. 209 Katherine Drive. Conway, AR
72032. (501) 329-5272.
Polycystic Ovarian Syndrome Association. P. O. Box 80517,
Portland, OR 97280. (877) 775-PCOS.
<www.pcosupport.org>.

Lori De Milto
Rebecca J. Frey, PhD

Ovarian torsion
Definition
Ovarian torsion is the twisting of the ovary due to
the influence of another condition or disease. This
results in extreme lower abdominal pain.
GALE ENCYCLOPEDIA OF MEDICINE

Ovarian torsion occurs infrequently only in females.
In can occur in women of all ages, but most women that
experience this are younger. Approximately 70-75% of
cases occur in women under 30 years old. About 20% of
all reported cases are in pregnant women. It is the fifth
most common gynecological emergency which can
include surgical intervention.
Ovarian torsion usually arises in only one ovary at
a time. They can occur in either normal or enlarged
ovaries and fallopian tubes, and occasionally they
develop in both.

KEY TERMS
Congenital—condition present at birth
Laparoscopy—endoscope used to observe structures in the abdomen
Mesosalpinx—a ligament connected to the fallopian tube
Ovary—female reproductive gland that contains
the ova (eggs)
Tachycardia—rapidly beating heart
Torsion—the action of twisting

Causes and symptoms
There are a variety of conditions that can cause
torsion of the ovary ranging from changes in normal
ovaries to congenital and developmental abnormalities or even a disease that affects the tube or ovary.
Normal ovaries that experience spasms or changes in
the blood vessels in the mesosalpinx can become
twisted. For example, if the veins in the mesosalpinx
become congested, the ovaries will undergo torsion.
Developmental abnormalities of the fallopian
tube such as extremely longer-than-normal tubes or a
missing mesosalpinx will cause ovarian torsion.
Diseases such as ovarian cysts or fibromas, tumor of
the ovary or tubes, and trauma to either the ovaries or
the tubes will also cause ovarian torsion.
The characteristic symptom of ovarian torsion is
the sudden onset of extreme lower abdominal pain that
radiates to the back, side and thigh. Nausea, vomiting,
diarrhea, and constipation can accompany the pain.
The patient may also experience tenderness in the
lower abdominal area, a mild fever and tachycardia.

Diagnosis
The diagnosis of ovarian torsions usually occurs
in an emergency room due to the suddenness of
extreme pain. Emergency room physicians may consult with another physician specializing in obstetrics
and gynecology. Since 20% of ovarian torsions occur
in pregnant women, physicians will order a pregnancy
test. Visualization with an ultrasound and CT scan
(computed tomography) will help pinpoint the ovarian structures and allow physicians to diagnose.
Diagnosis is often confirmed through laparoscopy.

Treatment
Ovarian torsions need to be repaired. This is done
through surgery, and for less severe cases laparoscopic
GALE ENCYCLOPEDIA OF MEDICINE

surgery is used. Medications such as NSAIDs are
given to control pain.

Prognosis
If ovarian torsions are diagnosed and treated
early, then the prognosis is favorable. However, if
diagnosis is delayed, the torsions can worsen and cut
off arterial blood flow into and venous blood flow out
of the ovary. This results in necrosis (death) of the
ovarian tissue. Delayed diagnosis can also result in
problems when trying to conceive due to infertility.

Prevention
Currently, there are no known methods for
prevention of ovarian torsion.
Sally C. McFarlane-Parrott

Ovary and fallopian tube removal see
Salpingo-oophorectomy
Ovary removal see Oophorectomy

Overactive bladder
Definition
Overactive bladder is the leakage of large amounts
of urine at unexpected times, including during sleep.

Description
People who lose urine for no apparent reason
while suddenly feeling the need or urge to urinate
2741

Overactive bladder

Description

Overactive bladder

may have overactive bladder. The condition effects
17 million Americans. The most common cause of
overactive bladder is inappropriate bladder contractions. Medical professionals describe such a bladder
as ‘‘unstable,’’ ‘‘spastic,’’ or ‘‘overactive.’’ A doctor
might call the condition ‘‘reflex incontinence’’ if it
results from overactive nerves controlling the bladder.
Having an overactive bladder can mean that the bladder empties during sleep, after drinking a small
amount of water, or when touching water or hearing
it running (as when someone else is taking a shower
or washing dishes). Involuntary actions of bladder
muscles can occur because of damage to the nerves
of the bladder, to the nervous system (spinal cord and
brain), or to muscles themselves. Multiple sclerosis,
Parkinson’s disease, Alzheimer’s disease, stroke, brain
tumors, and injury—including injury that occurs during surgery—all can harm bladder nerves or muscles.

Causes and symptoms
People with overactive bladder lose urine as soon
as they feel a strong need to go to the bathroom.
People with overactive bladder may leak urine:


When they can not get to the bathroom quickly enough



When they drink even a small amount of liquid, or
when they hear or touch running water

People with overactive bladder may also go to the
bathroom very often; for example, every two hours
during the day and night. They may even wet the bed.

Diagnosis
To diagnose the problem, a doctor will first ask
about symptoms and medical history. Other obvious
factors that can help define the problem include straining and discomfort, use of drugs, recent surgery, and
illness. If the patient’s medical history does not define
the problem, it will at least suggest which tests are
needed. The doctor will physically examine the patient
for signs of medical conditions causing the overactive
bladder, such as tumors that block the urinary tract,
stool impaction, and poor reflexes or sensations, which
may be evidence of a nerve-related cause. Overactive
bladder is often treated by general or family practicioners but the patient may be referred to a urologist,
who specializes in the urinary tract, or a urogynecologist, who focuses on urological problems in women.



Cystoscopy to look for abnormalities in the bladder
and lower urinary tract. It works by inserting a small
tube into the bladder that has a telescope for the
doctor to look through



Post-void residual (PVR) measurement to see how
much urine is left in the bladder after urinating by
placing a small soft tube into the bladder or by using
ultrasound (sound waves)



Urinalysis to examine urine for signs of infection,
blood, or other abnormalities



Urodynamic testing to examine bladder and urethral
sphincter function (may involve inserting a small
tube into the bladder; x rays also can be used to see
the bladder)

Treatment
Medications can reduce many types of leakage.
Some drugs inhibit contractions of an overactive bladder. Others, such as solifenacin succinate (Vesicare),
relax muscles, leading to more complete bladder emptying during urination. Some drugs tighten muscles at
the bladder neck and urethra, preventing leakage.
Among the drugs used are oxybutynin (Ditropan
XL), 5-30 mg daily; solifenacin (Vesicare), 5-10 mg
a day; darifenacin (Enablex), 3.75-15 mg daily; and
tolterodine (Detrol), 2-4 mg daily. A one-month supply of these drugs costs $90-125. Some medications,
especially hormones such as estrogen, are believed
to cause muscles involved in urination to function
normally. Some of these medications can produce
harmful side effects if used for long periods. In particular, estrogen therapy has been associated with an
increased risk for cancers of the breast and the lining
of the uterus. Patients should talk to their doctor
about the risks and benefits of long-term use of
medications.

Alternative treatment

Common tests used to diagnose overactive bladder include:

Adjusting dietary habits and avoiding acidic
and spicy foods, alcohol, caffeine, and other bladder
irritants can help to prevent urinary leaking. Eat
recommended amounts of whole grains, fruits, and
vegetables to avoid constipation. Bladder training,
used to treat urge incontinence, can also be a useful
treatment tool. The technique involves placing a
patient on a toileting schedule. The time interval
between urination is then gradually increased until
an acceptable time period between bathroom breaks
is consistently achieved.

Blood tests to examine blood for levels of various
chemicals

Biofeedback techniques can teach overactive bladder patients to control the urge to urinate.



2742

GALE ENCYCLOPEDIA OF MEDICINE

Alzheimer’s disease—A degenerative disorder that
affects the brain and causes dementia, especially
late in life.
Biofeedback—The use of monitoring devices that
display information about the operation of a bodily
function, for example, heart rate or blood pressure,
that is not normally consciously controlled.
Cystoscopy—The use of a narrow tubular instrument that is passed through the urethra to examine
the interior of the urethra and the urinary bladder.
Estrogen—Any of several steroid hormones, produced mainly in the ovaries, that stimulate estrus
and the development of female secondary sexual
characteristics.
Multiple sclerosis—A serious progressive disease
of the central nervous system.
Parkinson’s disease—An incurable nervous disorder
marked by the symptoms of trembling hands, lifeless
face, monotone voice, and a slow, shuffling walk.
Sphincter—A circular band of muscle that surrounds an opening or passage in the body and
narrows or closes the opening by contracting.
Urethal—Referring to the tube in humans that carries urine from the bladder out of the body.
Urogynecologist—A physician that deals with
women’s health, especially with the health of
women’s reproductive organs and urinary tract.
Urologist—A physician who deals with the study
and treatment of disorders of the urinary tract in
women and the urogenital system in men.

Biofeedback uses sensors to monitor temperature and
muscle contractions in the vagina to help overactive
bladder patients learn to increase their control over the
pelvic muscles.
An infusion, or tea, of horsetail (Equisetum
arvense), agrimony (Agrimonia eupatoria), and sweet
sumach (Rhus aromatica) may be prescribed by an
herbalist or naturopath to an overactive bladder.
These herbs are natural astringents, and encourage toning of the digestive and urinary tracts. Other herbs, such
as urtica, or stinging nettle (Urtica urens), plantain
(Plantago major), or maize (Zea mays) may be helpful.
Homeopathic remedies may include pulsatilla and causticum. Chinese herbalists might recommend golden
lock tea, a mixture of several herbs that helps the
body retain fluids.
GALE ENCYCLOPEDIA OF MEDICINE

With proper treatment, the prognosis for controlling the disorder is very good. There is no cure for
overactive bladder.

Prevention
There are no known preventative measures for
overactive bladder.
Resources
BOOKS

Ellsworth, Pamela. 100 Q & A About Overactive Bladder and
Urinary Incontinence. Boston: Jones and Bartlett
Publishers, 2005.
Newman, Diane K., and Alan J. Wein. Overcoming
Overactive Bladder: Your Complete Self-Care Guide.
Oakland, CA: New Harbinger Publications, 2004.
PERIODICALS

Perry, Patrick. ‘‘On Tour With Debbie Reynolds: The Feisty
and Fit Actress Speaks Out About an All-TooCommon Problem—Overactive Bladder.’’Saturday
Evening Post (January-February 2003): 26-27.
Radley, Stephen, and Maggi Saunders. ‘‘Sex and the
Overactive Bladder: Stephen Radley and Maggi
Saunders Discuss the Treatment of Patients With an
Overactive Bladder in Primary Care.’’Primary Health
Care (October 2004): 13-14.
Weiss, Barry D. ‘‘Selecting Medications for the Treatment of
Urinary Incontinence.’’American Family Physician
(January 15, 2005): 315.
Zepf, Bill. ‘‘Diagnosis and Management of Overactive
Bladder.’’American Family Physician (October 1, 2004):
1386.
ORGANIZATIONS

National Bladder Foundation. P.O. Box 1095, Ridgefield,
CT 06877. (877) 252-3337. debsla@aol.com. http://
www.bladder.org.

Ken R. Wells

Overhydration
Definition
Overhydration, also called water excess or water
intoxication, is a condition in which the body contains
too much water.
2743

Overhydration

Prognosis

KEY TERMS

Overhydration

Description
Overhydration occurs when the body takes in
more water than it excretes and its normal sodium
level is diluted. This can result in digestive problems,
behavioral changes, brain damage, seizures, or coma.
An adult whose heart, kidneys, and pituitary gland are
functioning properly would have to drink more than
two gallons of water a day to develop water intoxication. This condition is most common in patients whose
kidney function is impaired and may occur when
doctors, nurses, or other healthcare professionals
administer greater amounts of water-producing fluids
and medications than the patient’s body can excrete.
Overhydration is the most common electrolyte imbalance in hospitals, occurring in about 2% of all
patients.
Infants seem to be at greater risk for developing
overhydration. The Centers for Disease Control and
Prevention has declared that babies are especially susceptible to oral overhydration during the first month
of life, when the kidneys’ filtering mechanism is too
immature to excrete fluid as rapidly as older infants
do. Breast milk or formula provide all the fluids a
healthy baby needs. Water should be given slowly,
sparingly, and only during extremely hot weather.
Overhydration, which has been cited as a hazard of
infant swimming lessons, occurs whenever a baby
drinks too much water, excretes too little fluid, or
consumes and retains too much water.

Causes and symptoms
Drinking too much water rarely causes overhydration when the body’s systems are working normally. People with heart, kidney, or liver disease are
more likely to develop overhydration because their
kidneys are unable to excrete water normally. It may
be necessary for people with these disorders to restrict
the amount of water they drink and/or adjust the
amount of salt in their diets.
Since the brain is the organ most susceptible to
overhydration, a change in behavior is usually the first
symptom of water intoxication. The patient may
become confused, drowsy, or inattentive. Shouting
and delirium are common. Other symptoms of overhydration may include blurred vision, muscle cramps
and twitching, paralysis on one side of the body, poor
coordination, nausea and vomiting, rapid breathing,
sudden weight gain, and weakness. The patient’s complexion is normal or flushed. Blood pressure is sometimes higher than normal, but elevations may not
be noticed even when the degree of water intoxication
is serious.
2744

Overhydration can cause acidosis (a condition in
which blood and body tissues have an abnormally
high acid content), anemia, cyanosis (a condition that
occurs when oxygen levels in the blood drop sharply),
hemorrhage, and shock. The brain is the organ most
vulnerable to the effects of overhydration. If excess
fluid levels accumulate gradually, the brain may be
able to adapt to them and the patient will have only
a few symptoms. If the condition develops rapidly,
confusion, seizures, and coma are likely to occur.
Risk factors
Chronic illness, malnutrition, a tendency to retain
water, and kidney diseases and disorders increase the
likelihood of becoming overhydrated. Infants and the
elderly seem to be at increased risk for overhydration,
as are people with certain mental disorders or
alcoholism.

Diagnosis
Before treatment can begin, a doctor must determine whether a patient’s symptoms are due to overhydration, in which excess water is found within and
outside cells, or excess blood volume, in which high
sodium levels prevent the body from storing excess
water inside the cells. Overhydration is characterized
by excess water both within and around the body’s
cells, while excess blood volume occurs when the body
has too much sodium and can not move water to reservoirs within the cells. In cases of overhydration, symptoms of fluid accumulation do not usually occur. On
the other hand, in cases of excess blood volume, fluid
tends to accumulate around cells in the lower legs,
abdomen, and chest. Overhydration can occur alone
or in conjunction with excess blood volume, and differentiating between these two conditions may be
difficult.

Treatment
Mild overhydration can generally be corrected by
following a doctor’s instructions to limit fluid intake.
In more serious cases, diuretics may be prescribed to
increase urination, although these drugs tend to be
most effective in the treatment of excess blood volume.
Identifying and treating any underlying condition
(such as impaired heart or kidney function) is a priority, and fluid restrictions are a critical component of
every treatment plan.
In patients with severe neurologic symptoms, fluid
imbalances must be corrected without delay. A powerful diuretic and fluids to restore normal sodium
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Mild water intoxication is usually corrected by
drinking less than a quart of water a day for several
days. Untreated water intoxication can be fatal, but
this outcome is quite rare.
Resources

body. Ozone inactivates many disease bacteria and
viruses.

Purpose
Oxygen and ozone therapies are thought to benefit patients in the following ways:


stimulating white blood cell production



killing viruses (ozone and hydrogen peroxide)



improving the delivery of oxygen from the blood
stream to the tissues of the body



speeding up the breakdown of petrochemicals



increasing the production of interferon and tumor
necrosis factor, thus helping the body to fight infections and cancers



increasing the efficiency of antioxidant enzymes



increasing the flexibility and efficiency of the membranes of red blood cells



speeding up the citric acid cycle, which in turn stimulates the body’s basic metabolism

BOOKS

McPhee, Stephen, et al., editors. Current Medical
Diagnosisand Treatment, 1998. 37th ed. Stamford:
Appleton & Lange, 1997.

Maureen Haggerty

Oxycodo see Analgesics, opioid
Oxygen inhalation therapy see Oxygen/
ozone therapy

Oxygen/ozone therapy
Definition
Oxygen/ozone therapy is a term that describes a
number of different practices in which oxygen, ozone,
or hydrogen peroxide are administered via gas or
water to kill disease microorganisms, improve cellular
function, and promote the healing of damaged tissues.
The rationale behind bio-oxidative therapies, as they
are sometimes known, is the notion that as long as
the body’s needs for antioxidants are met, the use of
certain oxidative substances will stimulate the movement of oxygen atoms from the bloodstream to the
cells. With higher levels of oxygen in the tissues,
bacteria and viruses are killed along with defective
tissue cells. The healthy cells survive and multiply
more rapidly. The result is a stronger immune system.
Ozone itself is a form of oxygen, O3, produced
when ultraviolet light or an electric spark passes
through air or oxygen. It is a toxic gas that creates
free radicals, the opposite of what antioxidant vitamins do. Oxidation, however, is good when it occurs in
harmful foreign organisms that have invaded the
GALE ENCYCLOPEDIA OF MEDICINE

Description
Origins
The various forms of oxygen and ozone therapy
have been in use since the late nineteenth century. The
earliest recorded use of oxygen to treat a patient was
by Dr. J. A. Fontaine in 1879. In the 1950s, hyperbaric
oxygen treatment was used by cancer researchers. The
term ‘‘hyperbaric’’ means that the oxygen is given
under pressure higher than normal air pressure.
Recently, oxygen therapy has also been touted as a
quick purification treatment for mass-market consumers. Oxygen bars can be found in airports and large
cities, and provide pure oxygen in 20-minute sessions
for approximately $16. While proponents claim that
breathing oxygen will purify the body, most medical
doctors do not agree. What is more, oxygen can be
harmful to people with severe lung diseases, and these
people should never self-treat with oxygen.
Ozone has been used since 1856 to disinfect operating rooms in European hospitals, and since 1860 to
purify the water supplies of several large German
cities. Ozone was not, however, used to treat patients
until 1915, when a German doctor named Albert
Wolff began to use it to treat skin diseases. During
World War I, the German Army used ozone to treat
wounds and anaerobic infections. In the 1950s, several
German physicians used ozone to treat cancer alongside mainstream therapeutic methods. It is estimated
2745

Oxygen/ozone therapy

concentrations are administered rapidly at first. When
the patient has absorbed 50% of the therapeutic
substances, blood levels are measured. Therapy is continued at a more moderate pace in order to prevent
brain damage as a result of sudden changes in blood
chemistry.

Oxygen/ozone therapy

that as of the late 1990s, about 8,000 practitioners in
Germany were using ozone in their practices. This
figure includes medical doctors as well as naturopaths
and homeopaths.
Hydrogen peroxide is familiar to most people as an
over-the-counter preparation that is easily available at
supermarkets as well as pharmacies, and is used as an
antiseptic for cleansing minor cuts and scrapes. It was
first used as an intravenous infusion in 1920 by a
British physician in India, T. H. Oliver, to treat a
group of 25 Indian patients who were critically ill
with pneumonia. Oliver’s patients had a mortality rate
of 48%, compared to the standard mortality rate of
80% for the disease. In the 1920s, an American physician named William Koch experimented with hydrogen peroxide as a treatment for cancer. He left the
United States after a legal battle with the FDA. In the
early 1960s, researchers at Baylor University studied
the effects of hydrogen peroxide in removing plaque
from the arteries as well as its usefulness in treating
cancer, but their findings were largely ignored.
Oxygen, ozone, and hydrogen peroxide are used
therapeutically in a variety of different ways.
Hyperbaric oxygen therapy (HBO)
Hyperbaric oxygen therapy (HBO) involves putting the patient in a pressurized chamber in which he
or she breathes pure oxygen for a period of 90 minutes
to two hours. HBO may also be administered by using
a tight-fitting mask, similar to the masks used for
anesthesia. A nasal catheter may be used for small
children.
Ozone therapy
Ozone therapy may be administered in a variety
of ways.


Intramuscular injection: A mixture of oxygen and
ozone is injected into the muscles of the buttocks.



Rectal insufflation: A mixture of oxygen and ozone is
introduced into the rectum and absorbed through the
intestines.



Autohemotherapy: Between 10–15 mL of the
patient’s blood is removed, treated with a mixture
of oxygen and ozone and reinjected into the patient.



Intra-articular injection: Ozone-treated water is
injected into the patient’s joints to treat arthritis,
rheumatism and other joint diseases.



Ozonated water: Ozone is bubbled through water
that is used to cleanse wounds, burns, and skin infections, or to treat the mouth after dental surgery.

2746



Ozonated oil: Ozone is bubbled through olive or
safflower oil, forming a cream that is used to treat
fungal infections, insect bites, acne, and skin
problems.



Ozone bagging: Ozone and oxygen are pumped into
an airtight bag that surrounds the area to be treated,
allowing the body tissues to absorb the mixture.
Hydrogen peroxide

Hydrogen peroxide may be administered intravenously in a 0.03% solution. It is infused slowly into
the patient’s vein over a period of one to three hours.
Treatments are given about once a week for chronic
illness but may be given daily for such acute illnesses
as pneumonia or influenza. A course of intravenous
hydrogen peroxide therapy may range from one to
20 treatments, depending on the patient’s condition
and the type of illness being treated. Injections of
0.03% hydrogen peroxide have also been used to
treat rheumatoid and osteoarthritis. The solution is
injected directly into the inflamed joint.
Hydrogen peroxide is also used externally to treat
stiff joints, psoriasis, and fungal infections. The patient
soaks for a minimum of 20 minutes in a tub of warm
water to which 1 pint of 35% food-grade hydrogen
peroxide (a preparation used by the food industry as a
disinfectant) has been added.

Preparations
Oxygen is usually delivered to the patient as a gas;
ozone as a gas mixed with oxygen or bubbled through
oil or water; and hydrogen peroxide as an 0.03%
solution for intravenous injection or a 35% solution
for external hydrotherapy.

Precautions
Patients interested in oxygen/ozone therapies
must consult with a physician before receiving treatment. Hyperbaric oxygen treatment should not be
given to patients with untreated pneumothorax, a
condition in which air or gas is present in the cavity
surrounding the lungs. Patients with a history of pneumothorax, chest surgery, emphysema, middle ear surgery, uncontrolled high fevers, upper respitory
infections, seizures, or disorders of the red blood cells
are not suitable candidates for oxygen/ozone therapy.
In addition, patients should be aware that oxygen is
highly flammable. If treatments are administered
incorrectly or by an unskilled person, there is a risk
of fire.
GALE ENCYCLOPEDIA OF MEDICINE

Autohemotherapy—A form of ozone therapy in
which a small quantity of the patient’s blood is
withdrawn, treated with a mixture of ozone and
oxygen, and reinfused into the patient.
Hydrogen peroxide—A colorless, unstable compound of hydrogen and oxygen (H2O2). An aqueous solution of hydrogen peroxide is used as an
antiseptic and bleaching agent.
Hyperbaric oxygen therapy (HBO)—A form of
oxygen therapy in which the patient breathes
oxygen in a pressurized chamber.
Ozone—A form of oxygen with three atoms in its
molecule (O3), produced by an electric spark or
ultraviolet light passing through air or oxygen.
Ozone is used therapeutically as a disinfectant
and oxidative agent.

Recent European research in ozone therapy
includes studies in the oxygenation of resting muscles,
the treatment of vascular disorders, and the relief of
pain from herniated lumbar disks. No corresponding
studies are being done in the United States as of late
2003.
Resources
PERIODICALS

Andreula, C. F., L. Simonetti, F. De Santis, et al.
‘‘Minimally Invasive Oxygen-Ozone Therapy for
Lumbar Disk Herniation.’’ American Journal of
Neuroradiology 24 (May 2003): 996–1000.
Clavo, B., J. L. Perez, L. Lopez, et al. ‘‘Effect of Ozone
Therapy on Muscle Oxygenation.’’ Journal of
Alternative and Complementary Medicine 9 (April
2003): 251–256.
Tylicki, L., T. Nieweglowski, B. Biedunkiewicz, et al. ‘‘The
Influence of Ozonated Autohemotherapy on Oxidative
Stress in Hemodialyzed Patients with Atherosclerotic
Ischemia of Lower Limbs.’’ International Journal of
Artificial Organs 26 (April 2003): 297–303.
ORGANIZATIONS

Side effects
Typical side effects of oxygen or ozone therapy
can include elevated blood pressure and ear pressure
similar to that experienced while flying. Side effects
may also include headache, numbness in the fingers,
temporary changes in the lens of the eye, and
seizures.

Research and general acceptance
Oxygen/ozone therapies are far more widely
accepted in Europe than in the United States. The
most intensive research in these therapies is presently
being conducted in the former Soviet Union and in
Cuba. In the United States, the work of the Baylor
researchers was not followed up. In 2000, the Office
of Alternative Medicine of the National Institutes
of Health (presently the National Center for
Complementary and Alternative Medicine, or
NCCAM) indicated interest in conducting clinical
trials of oxygen/ozone therapies; as of 2003, however,
these studies have not been carried out.

GALE ENCYCLOPEDIA OF MEDICINE

International Bio-Oxidative Medicine Foundation
(IBOMF). P.O. Box 891954. Oklahoma City, OK
73109. (405) 634-7855. Fax (405) 634-7320.
International Ozone Association, Ind. Pan American
Group. 31 Strawberry Hill Ave. Stamford, CT 06902.
(203) 348-3542. Fax (203) 967-4845.
NIH National Center for Complementary and Alternative
Medicine (NCCAM). NCCAM Clearinghouse. P. O.
Box 8218. Silver Spring, MD 20907-8218. TTY/TDY:
(888) 644-6226. <http://nccam.nih.gov>.
OTHER

Oxygen Healing Therapies. <http://www.oxygen
healingtherapies.com>.

Amy Cooper
Rebecca J. Frey, PhD

Oxymetazoline see Decongestants
Oxytocin see Drugs used in labor
Ozone therapy see Oxygen/ozone therapy

2747

Oxygen/ozone therapy

KEY TERMS

P
PAC see Atrial ectopic beats
Pacemaker implantation see Pacemakers

Pacemakers
Definition
A pacemaker is a surgically-implanted electronic
device that regulates a slow or erratic heartbeat.

Purpose
Pacemakers are implanted to regulate irregular
contractions of the heart (arrhythmia). They are most
frequently prescribed to speed the heartbeat of patients
who have a heart rate well under 60 beats per minute
(severe symptomatic bradycardia). They are also used
in some cases to slow a fast heart rate (tachycardia).

Precautions
The symptoms of fatigue and lightheadedness that
are characteristic of bradycardia can also be caused by
a number of other medical conditions, including anemia. Certain prescription medications can also slow
the heart rate. A doctor should take a complete medical history and perform a full physical work-up to rule
out all non-cardiac causes of bradycardia.
Patients with cardiac pacemakers should not
undergo a magnetic resonance imaging (MRI) procedure. Devices that emit electromagnetic waves (including magnets) may alter pacemaker programming or
functioning. A 1997 study found that cellular phones
often interfere with pacemaker programming and
cause irregular heart rhythm. However, advances in
pacemaker design and materials have greatly reduced
the risk of pacemaker interference from electromagnetic fields.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Approximately 500,000 Americans have an
implantable permanent pacemaker device. A pacemaker implantation is performed under local anesthesia
in a hospital by a surgeon assisted by a cardiologist. An
insulated wire called a lead is inserted into an incision
above the collarbone and guided through a large vein
into the chambers of the heart. Depending on the configuration of the pacemaker and the clinical needs of the
patient, as many as three leads may be used in a pacing
system. Current pacemakers have a double, or bipolar,
electrode attached to the end of each lead. The electrodes deliver an electrical charge to the heart to regulate
heartbeat. They are positioned on the areas of the heart
that require stimulation. The leads are then attached to
the pacemaker device, which is implanted under the
skin of the patient’s chest.
Patients undergoing surgical pacemaker implantation usually stay in the hospital overnight. Once the
procedure is complete, the patient’s vital signs are
monitored and a chest x ray is taken to ensure that
the pacemaker and leads are properly positioned.
Modern pacemakers have sophisticated programming capabilities and are extremely compact. The
smallest weigh less than 13 grams (under half an
ounce) and are the size of two stacked silver dollars.
The actual pacing device contains a pulse generator,
circuitry programmed to monitor heart rate and deliver stimulation, and a lithiumiodide battery. Battery
life typically ranges from seven to 15 years, depending
on the number of leads the pacemaker is configured
with and how much energy the pacemaker uses. When
a new battery is required, the unit can be exchanged in
a simple outpatient procedure.
A temporary pacing system is sometimes recommended for patients who are experiencing irregular
heartbeats as a result of a recent heart attack or other
acute medical condition. The implantation procedure
for the pacemaker leads is similar to that for a
2749

Pacemakers

KEY TERMS
Electrocardiogram (ECG)—A recording of the
electrical activity of the heart. An ECG uses externally attached electrodes to detect the electrical
signals of the heart.
Electrophysiological study—A test that monitors
the electrical activity of the heart in order to diagnose arrhythmia. An electrophysiological study
measures electrical signals through a cardiac catheter that is inserted into an artery in the leg and guided
up into the atrium and ventricle of the heart.
Embolism—A blood clot, air bubble, or clot of
foreign material that blocks the flow of blood in an
artery. When an embolism blocks the blood supply
to a tissue or organ, the tissue the artery feeds dies
(infarction). Without immediate and appropriate
treatment, an embolism can be fatal.
Pacemakers like these are usually implanted under the skin
below the collarbone. The pacemaker is connected to the
heart by a wire inserted into a major vein in the neck and
guided down into the heart. (Photograph by Eamonn McNulty,
Photo Researchers, Inc. Reproduced by permission.)

permanent pacing system, but the actual pacemaker
unit housing the pulse generator remains outside the
patient’s body. Temporary pacing systems may be
replaced with a permanent device at a later date.

Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.

batteries must be checked regularly. Some pacing
systems allow patients to monitor battery life through
a special telephone monitoring service that can read
pacemaker signals.

Preparation
Patients being considered for pacemaker implantation will undergo a full battery of cardiac tests,
including an electrocardiogram (ECG) or an electrophysiological study or both to fully evaluate the
bradycardia or tachycardia.
Patients are advised to abstain from eating 6-8
hours before the surgical procedure. The patient is
usually given a sedative to help him or her relax for
the procedure. An intravenous (IV) line will also be
inserted into a vein in the patient’s arm before the
procedure begins in case medication or blood products
are required during the insertion.

Aftercare
Pacemaker patients should schedule a follow-up
visit with their cardiologist approximately six weeks
after the surgery. During this visit, the doctor will
make any necessary adjustments to the settings of the
pacemaker. Pacemakers are programmed externally
with a handheld electromagnetic device. Pacemaker
2750

Risks
Because pacemaker implantation is an invasive
surgical procedure, internal bleeding, infection,
hemorrhage, and embolism are all possible complications. Infection is more common in patients with
temporary pacing systems. Antibiotic therapy given
as a precautionary measure can reduce the risk of
pacemaker infection. If infection does occur, the entire
pacing system may have to be removed.
The placing of the leads and electrodes during the
implantation procedure also presents certain risks for
the patient. The lead or electrode could perforate the
heart or cause scarring or other damage. The electrodes can also cause involuntary stimulation of nearby
skeletal muscles.
A complication known as pacemaker syndrome
develops in approximately 7% of pacemaker patients
with single-chamber pacing systems. The syndrome is
characterized by the low blood pressure and dizziness
that are symptomatic of bradycardia. It can usually be
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Pacemakers that are properly implanted and programmed can correct a patient’s arrhythmia and
resolve related symptoms.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Paula Anne Ford-Martin

Packed cell volume see Hematocrit
Packed red blood cell volume see
Hematocrit

Paget’s disease of bone
Definition
Paget’s disease of bone (osteitis deformans) is the
abnormal formation of bone tissue that results in
weakened and deformed bones.

Description
Named for Sir James Paget (1814–1899), this
disease affects 1–3% of people over 50 years of age,
but affects over 10% of people over 80 years of age.
Paget’s disease can affect one or more bones in the
body. Most often, the pelvis, bones in the skull, the
long bones (the large bones that make up the arms and
legs), and the collarbones are affected by Paget’s disease. In addition, the joints between bones (the knees
or elbows, for example) can develop arthritis because
of this condition.
Paget’s disease is characterized by changes in the
normal mechanism of bone formation. Bone is a living
material made by the body through the continual
processes of formation and breakdown (resorption).
The combination of these two actions is called remodeling and is used by the body to build bone tissue that
is strong and healthy. Strong bones are formed when
bone tissue is made up of plate-shaped crystals of
minerals called hydroxyapatite. Normal wear and
tear on the skeletal system is repaired throughout life
GALE ENCYCLOPEDIA OF MEDICINE

by the ongoing process of remodeling. In fact, the
entire human skeleton is remodeled every five years.
Healthy bone tissue has an ordered structure that
gives the bone its strength. Bones affected by Paget’s
disease, however, have a structure that is disorganized.
This disorganized structure weakens the diseased bone
and makes people suffering from this disease more
likely to have fractures. These fractures are slow to heal.
Paget’s disease of bone is most commonly found
in Europe, England, Australia, New Zealand, and
North America. In these areas, up to 3% of all people
over 55 years of age are affected with the disease. It is
interesting to note that Paget’s disease is rare in Asia,
possibly showing that this disease may affect some
ethnic groups and geographic areas more than others.

Causes and symptoms
The cause of Paget’s disease is not known. Various
viruses have been suggested to be involved in this
disease, but the relationship between viral infections
and Paget’s disease remains uncertain. There also may
to be a genetic component to this disease since it may
appear in more than one person within the same family.
Paget’s disease usually begins without any symptoms. And, in its early stages, the symptoms that do
occur are often confused with symptoms of arthritis.
However, as the disease progresses, bone and joint
pain develop. A unique feature of Paget’s disease is
the enlargement of areas of affected bone. This type of
enlargement is clearly identifiable on an x ray.
If the bones of the skull are affected by Paget’s
disease, enlargement of the skull can occur and may
result in a loss of hearing. When the long bones in the
legs are affected, they can become bent under the
body’s weight because of their weakness. Little or no
injury to a bone can cause fractures in the weakened
bones. Fractures that occur when no traumatic injury
is present are known as spontaneous fractures.
Although rare, bone cancer occurs in less than 1% of
patients with Paget’s disease. Such cancer is often accompanied by an abrupt increase in the intensity of pain at
the diseased site. Unfortunately, this type of cancer has
a poor prognosis; the average survival time from the
onset of symptoms is generally one to three years.

Diagnosis
Paget’s disease is often found when an individual
is having x rays taken for medical reasons unrelated to
this bone disease. A diagnosis of Paget’s disease can
also be made when higher than normal levels of a
2751

Paget’s disease of bone

corrected by the implantation of a dual-chamber
pacing system.

Paget’s disease of bone

to treat Paget’s disease. This chemical rapidly decreases
the amount of bone breakdown or loss (resorption).
After approximately two to three weeks of treatment
with extra calcitonin, bone pain lessens and new bone
tissue forms. Calcitonin is commonly given as daily
injections for one month, followed by three injections
each week for several additional months. The total dose
of calcitonin given to an individual depends upon the
amount of disease present and how well the individual’s
condition responds to the treatment.
Although calcitonin is effective in slowing the progression of Paget’s disease, the favorable effects of the
drug do not continue for very long once administration
of the drug is stopped. In addition, some temporary side
effects can occur with this drug. Nausea and flushing are
the most common side effects and have been found in
20-30% of individuals taking calcitonin. Vomiting,
diarrhea, and abdominal pain can also occur, but these
effects are also temporary. A form of calcitonin taken
nasally causes fewer side effects, but requires higher
doses because less of the drug reaches the diseased bone.

This woman’s legs are bowed due to Paget’s disease. (Custom
Medical Stock Photo. Reproduced by permission.)

chemical called alkaline phosphatase are found in the
blood. Alkaline phosphatase is a substance involved in
the bone formation process, so if its levels are abnormally high this indicates that the balance between
bone formation and resorption is upset.

Treatment
Treatment, given only when symptoms are present, consists of the following types:
Drugs
Paget’s disease is most often treated with drug
therapy, with bone pain lessening within weeks of
starting the treatment. While non-steroidal antiinflammatory drugs can reduce bone pain, two additional categories of drugs are used to treat this disease.
HORMONE TREATMENT. Calcitonin, a hormone
which is made naturally by the thyroid gland, is used

2752

BISPHOSPHONATES. The bisphosphonate group of
drugs are drugs that bind directly to bone minerals
because of their specific chemical structure. Once
bound to the bone, these drugs inhibit bone loss by
reducing the action of bone cells that normally
degrade bone during the remodeling process. Unlike
treatment with calcitonin, the positive effects of
increased bone formation and reduced pain can
continue for many months or even years after bisphosphonate treatment is stopped. Bisphosphonates are
considered the treatment of choice for Paget’s disease
and are usually given for 3-6 months at a time.

Bisphosphonate drugs suitable for the treatment of
Paget’s disease are alendronate, clodronate, etidronate,
pamidronate, risedronate, and tiludronate. The main
side effects of these drugs include a flu-like reaction
(pamidronate), gastrointestinal disturbances (alendronate, clodronate), and abnormal bone formation
(etidronate, when taken in high doses). Risedronate is
the newest of these drugs. It is about 1,000 times more
potent than etidronate and 3 to 5 times more potent
than alendronate. Because of the greater potency of this
drug, lower doses and a shorter duration of treatment
are required. This leads to fewer side effects with similar, or better, clinical results in the patient.
Surgery
Treatment of Paget’s disease usually begins with
drug therapy. However, various surgical treatments
can also be used to treat skeletal conditions that
occur in patients with Paget’s disease.
GALE ENCYCLOPEDIA OF MEDICINE

Bisphosphonate—A class of drugs used to treat
Paget’s disease. These drugs bind to the minerals
in bone tissue and lessen the amount of bone loss
associated with Paget’s disease.
Calcitonin—A naturally occurring hormone made
by the thyroid gland that can be used as a drug to
treat Paget’s disease.
Remodeling—The ongoing process of bone formation and breakdown that results in healthy bone
development.

In patients with severe arthritis of the hip or
knee, a joint replacement operation can be beneficial.
However, in addition to the malformation of bone
tissue caused by this condition, there are greater
numbers of blood vessels that form in the diseased
bone relative to a healthy bone. This makes surgery
on bones affected with Paget’s disease more difficult.

Paget’s disease of the breast may also be called
mammary Paget’s disease (MPD). There is a much
rarer form of this disease called extramammary
Paget’s disease (EMPD). MPD affects the breast nipple and is also called Paget’s disease of the nipple.
EMPD can affect the skin of the external genital tissues in both women and men, as well as the skin of the
eyelids and external ear canal. MPD is believed to
develop from a tumor growth within the milk ducts
of the breast. EMPD may represent a spreading
(metastasis) of MPD to other parts of the body.

Causes and symptoms
The cause of Paget’s disease of the breast is
unknown, but it is usually associated with an underlying cancer of the breast.
The symptoms of Paget’s disease of the breast
include:


red scaly patches of skin on the nipple and sometimes
also on the dark area of skin around the nipple (areola)



crusting, bleeding, or ulceration of the skin of the
affected area



a discharge of fluid from the nipple



a turning inward (inversion) of the nipple

Prognosis
There is no cure for Paget’s disease. However, the
development of potent bisphosphonate drugs like risedronate has resulted in the ability to slow the progress
of the disease.
Paul A. Johnson, Ed.M.

In approximately 30-40 % of cases of Paget’s disease of the breast, there is also a detectable lump in the
breast.

Diagnosis

Paget’s disease of the breast
Definition
Paget’s disease of the breast is a rare form of
breast cancer which makes up approximately 1-4 %
of all breast tumors. While sharing its name with
Paget’s disease of bone, these are two medically unrelated conditions. They are simply named after the
same doctor who first described them.

Description
Paget’s disease of the breast is generally associated
with an underlying breast cancer. It is generally seen
in people between the ages of 40 and 80 years. Cases
in men have been identified, but they are extremely
rare.
GALE ENCYCLOPEDIA OF MEDICINE

Paget’s disease of the breast is often confused with
other skin conditions, such as eczema, dermatitis, or
psoriasis. These misdiagnoses often lead to delays in
appropriate treatment. Misdiagnosis is more common
when both breast are affected and no lump in the
breast is detected. When only one breast is affected,
or when the presence of a lump in the breast is also
detected, a correct initial diagnosis is more likely
to occur.
Once Paget’s disease of the breast is suspected,
it can be definitively confirmed by biopsy of the
affected tissue. In this procedure, a small piece of
the affected skin and the underlying tissue is removed
and sent to a laboratory for examination under a
microscope. The shape and other characteristics
of the cells in the biopsied sample will allow the
laboratory personnel to determine if the sample is
affected with Paget’s disease of the breast, or some
other condition.
2753

Paget’s disease of the breast

KEY TERMS

Pain

Prevention

KEY TERMS
Metastasis—The spread of a cancer from one part
of the body (where the cancer originated) to
another part of the body.
Ulceration—The formation of an ulcer, a patch of
tissue that is discontinuous with the surrounding
tissue because the tissue within the ulcer has
decayed or died and been swept away.

Because the cause of Paget’s disease of the breast
is not known, prevention of this disease is not possible.
In instances where this conditions arises from other
underlying cancers of the breast, it may be possible to
prevent Paget’s disease of the breast from occurring if
the underlying cause is diagnosed and successfully
treated prior to the development of Paget’s disease of
the breast.
Resources
BOOKS

Topical steroid creams are usually used to treat
eczema, dermatitis, and psoriasis. These creams will
have no effect on the skin conditions caused by Paget’s
disease of the breast.

Treatment
Surgery is the main treatment for Paget’s disease
of the breast. Removal of the breast (mastectomy)
may be recommended if the cancer is seen in a wide
area away from the nipple or appears to be deep into
the breast tissue. Breast conservation surgery, aimed
at keeping as much of the breast as possible, may be
recommended in cases where the disease is diagnosed
early enough and the cancer has not spread far from
the surface of the nipple.
Some people will require further treatment after
surgery. This treatment may include radiation therapy,
chemotherapy, or a combination of both. Radiation
therapy involves using high-energy x rays to destroy
any cancer cells that may remain after surgical removal
of the primary tumor. Radiation therapy is most common after breast conservation surgery. Chemotherapy
involves the use of medicinal drugs to destroy the
growth of any cancer cells that may remain after
removal of the primary cancer. Chemotherapy treatments are most common after mastectomy.

Love, Susan M., and Karen Lindsey. Dr. Susan Love’s
Breast Book. 3rd ed. Reading, MA: Perseus Book
Group, 2000.
PERIODICALS

Sheen-Chen, S.M., et al. ‘‘Paget Disease of the Breast - an
EasilyOverlooked Disease?’’ Journal of Surgical
Oncology 76 (April 2001): 261-5.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800)ACS-2345. <http://
www.cancer.org>.
National Alliance of Breast Cancer Organizations. 9 East
37th Street, 10th Floor, New York, NY 10016. (888) 8062226. Fax: 212-689-1213. <http://www.nabco.org/>.
National Breast Cancer Coalition. 1707 L Street Northwest,
Suite 1060, Washington, DC 20036. (800) 622-2838.
Fax: 202-265-6854. <http://www.natlbcc.org/>.
OTHER

Paget’s Disease of the Breast: The CancerBACUP Factsheet.
May 12, 2001. <http://www.cancerbacup.org.uk/
info/paget.htm>.
Ruth, Laura. Paget’s Disease: A Rare Form of Breast
Cancer. May 12, 2001. <http://users.cnmnetwork.com/
~lrs1/paget.htm>.

Paul A. Johnson, Ed.M.

Alternative treatment
Alternative treatments for Paget’s disease of the
breast include: the use of cartilage from cows or
sharks; a diet known as Gerson therapy; administration
of the chemicals hydrazine sulfate or laetrile; and, the
injection of solutions derived from the mistletoe plant.

Prognosis
The prognosis for Paget’s disease of the breast
depends on the underlying cancer that is causing this
condition and whether or not this cancer has spread
(metastasized) to other parts of the body.
2754

Pain
Definition
Pain is an unpleasant feeling that is conveyed to
the brain by sensory neurons. The discomfort signals
actual or potential injury to the body. However, pain
is more than a sensation, or the physical awareness
of pain; it also includes perception, the subjective
interpretation of the discomfort. Perception gives
information on the pain’s location, intensity, and
GALE ENCYCLOPEDIA OF MEDICINE

Description
Pain arises from any number of situations. Injury
is a major cause, but pain may also arise from an
illness. It may accompany a psychological condition,
such as depression, or may even occur in the absence
of a recognizable trigger.
Acute pain
Acute pain often results from tissue damage, such
as a skin burn or broken bone. Acute pain can also be
associated with headaches or muscle cramps. This type
of pain usually goes away as the injury heals or the
cause of the pain (stimulus) is removed.
To understand acute pain, it is necessary to understand the nerves that support it. Nerve cells, or neurons, perform many functions in the body. Although
their general purpose, providing an interface between
the brain and the body, remains constant, their
capabilities vary widely. Certain types of neurons are
capable of transmitting a pain signal to the brain.
As a group, these pain-sensing neurons are called
nociceptors, and virtually every surface and organ of
the body is wired with them. The central part of these
cells is located in the spine, and they send threadlike
projections to every part of the body. Nociceptors are
classified according to the stimulus that prompts them
to transmit a pain signal. Thermoreceptive nociceptors are stimulated by temperatures that are potentially tissue damaging. Mechanoreceptive nociceptors
respond to a pressure stimulus that may cause injury.
Polymodal nociceptors are the most sensitive and
can respond to temperature and pressure. Polymodal
nociceptors also respond to chemicals released by the
cells in the area from which the pain originates.
Nerve cell endings, or receptors, are at the front
end of pain sensation. A stimulus at this part of the
nociceptor unleashes a cascade of neurotransmitters
(chemicals that transmit information within the nervous system) in the spine. Each neurotransmitter has
a purpose. For example, substance P relays the pain
message to nerves leading to the spinal cord and brain.
These neurotransmitters may also stimulate nerves
leading back to the site of the injury. This response
prompts cells in the injured area to release chemicals
that not only trigger an immune response, but also
influence the intensity and duration of the pain.
GALE ENCYCLOPEDIA OF MEDICINE

Chronic and abnormal pain
Chronic pain refers to pain that persists after an
injury heals, cancer pain, pain related to a persistent
or degenerative disease, and long-term pain from an
unidentifiable cause. It is estimated that one in three
people in the United States will experience chronic
pain at some point in their lives. Of these people,
approximately 50 million are either partially or completely disabled.
Chronic pain may be caused by the body’s
response to acute pain. In the presence of continued
stimulation of nociceptors, changes occur within the
nervous system. Changes at the molecular level are
dramatic and may include alterations in genetic transcription of neurotransmitters and receptors. These
changes may also occur in the absence of an identifiable cause; one of the frustrating aspects of chronic
pain is that the stimulus may be unknown. For example, the stimulus cannot be identified in as many as
85% of individuals suffering lower back pain.
Scientists have long recognized a relationship
between depression and chronic pain. In 2004, a survey of California adults diagnosed with major depressive disorder revealed that more than one-half of them
also suffered from chronic pain.
Other types of abnormal pain include allodynia,
hyperalgesia, and phantom limb pain. These types of
pain often arise from some damage to the nervous
system (neuropathic). Allodynia refers to a feeling
of pain in response to a normally harmless stimulus.
For example, some individuals who have suffered
nerve damage as a result of viral infection experience
unbearable pain from just the light weight of their
clothing. Hyperalgesia is somewhat related to allodynia in that the response to a painful stimulus is
extreme. In this case, a mild pain stimulus, such as a
pin prick, causes a maximum pain response. Phantom
limb pain occurs after a limb is amputated; although
an individual may be missing the limb, the nervous
system continues to perceive pain originating from
the area.

Causes and symptoms
Pain is the most common symptom of injury and
disease, and descriptions can range in intensity from a
mere ache to unbearable agony. Nociceptors have
the ability to convey information to the brain that
indicates the location, nature, and intensity of the
pain. For example, stepping on a nail sends an information-packed message to the brain: the foot has
experienced a puncture wound that hurts a lot.
2755

Pain

something about its nature. The various conscious and
unconscious responses to both sensation and perception, including the emotional response, add further
definition to the overall concept of pain.

Pain

Pain perception also varies depending on the location of the pain. The kinds of stimuli that cause a pain
response on the skin include pricking, cutting, crushing, burning, and freezing. These same stimuli would
not generate much of a response in the intestine.
Intestinal pain arises from stimuli such as swelling,
inflammation, and distension.

Diagnosis
Pain is considered in view of other symptoms and
individual experiences. An observable injury, such as a
broken bone, may be a clear indicator of the type of
pain a person is suffering. Determining the specific
cause of internal pain is more difficult. Other symptoms, such as fever or nausea, help narrow down the
possibilities. In some cases, such as lower back pain, a
specific cause may not be identifiable. Diagnosis of the
disease causing a specific pain is further complicated
by the fact that pain can be referred to (felt at) a skin
site that does not seem to be connected to the site of
the pain’s origin. For example, pain arising from fluid
accumulating at the base of the lung may be referred to
the shoulder.
Since pain is a subjective experience, it may be very
difficult to communicate its exact quality and intensity
to other people. There are no diagnostic tests that can
determine the quality or intensity of an individual’s
pain. Therefore, a medical examination will include a
lot of questions about where the pain is located, its
intensity, and its nature. Questions are also directed at
what kinds of things increase or relieve the pain, how
long it has lasted, and whether there are any variations
in it. An individual may be asked to use a pain scale to
describe the pain. One such scale assigns a number to
the pain intensity; for example, 0 may indicate no pain,
and 10 may indicate the worst pain the person has
ever experienced. Scales are modified for infants and
children to accommodate their level of comprehension.

Treatment
There are many drugs aimed at preventing or treating pain. Nonopioid analgesics, narcotic analgesics,
anticonvulsant drugs, and tricyclic antidepressants
work by blocking the production, release, or uptake
of neurotransmitters. Drugs from different classes
may be combined to handle certain types of pain.
Nonopioid analgesics include common over-thecounter medications such as aspirin, acetaminophen
(Tylenol), and ibuprofen (Advil). These are most
often used for minor pain, but there are some prescription-strength medications in this class.
2756

Narcotic analgesics are only available with a doctor’s prescription and are used for more severe pain,
such as cancer pain. These drugs include codeine, morphine, and methadone. Addiction to these painkillers is
not as common as once thought. Many people who
genuinely need these drugs for pain control typically
do not become addicted. However, narcotic use should
be limited to patients thought to have a short life span
(such as people with terminal cancer) or patients whose
pain is only expected to last for a short time (such as
people recovering from surgery). In August 2004, the
Drug Enforcement Administration (DEA) issued
new guidelines to help physicians prescribe narcotics
appropriately without fear of being arrested for
prescribing the drugs beyond the scope of their medical
practice. DEA is trying to work with physicians to
ensure that those who need to drugs receive them but
to ensure opioids are not abused.
Anticonvulsants, as well as antidepressant drugs,
were initially developed to treat seizures and depression, respectively. However, it was discovered that
these drugs also have pain-killing applications.
Furthermore, since in cases of chronic or extreme
pain, it is not unusual for an individual to suffer
some degree of depression; antidepressants may serve
a dual role. Commonly prescribed anticonvulsants for
pain include phenytoin, carbamazepine, and clonazepam. Tricyclic antidepressants include doxepin, amitriptyline, and imipramine.
Intractable (unrelenting) pain may be treated by
injections directly into or near the nerve that is transmitting the pain signal. These root blocks may also be
useful in determining the site of pain generation. As the
underlying mechanisms of abnormal pain are uncovered, other pain medications are being developed.
Drugs are not always effective in controlling pain.
Surgical methods are used as a last resort if drugs and
local anesthetics fail. The least destructive surgical
procedure involves implanting a device that emits
electrical signals. These signals disrupt the nerve and
prevent it from transmitting the pain message.
However, this method may not completely control
pain and is not used frequently. Other surgical techniques involve destroying or severing the nerve, but
the use of this technique is limited by side effects,
including unpleasant numbness.

Alternative treatment
Both physical and psychological aspects of pain
can be dealt with through alternative treatment. Some
of the most popular treatment options include
acupressure and acupuncture, massage, chiropractic,
GALE ENCYCLOPEDIA OF MEDICINE

Acute pain—Pain in response to injury or another
stimulus that resolves when the injury heals or the
stimulus is removed.
Chronic pain—Pain that lasts beyond the term of an
injury or painful stimulus. Can also refer to cancer
pain, pain from a chronic or degenerative disease,
and pain from an unidentified cause.
Neuron—A nerve cell.
Neurotransmitters—Chemicals within the nervous
system that transmit information from or between
nerve cells.
Nociceptor—A neuron that is capable of sensing
pain.
Referred pain—Pain felt at a site different from the
location of the injured or diseased part of the body.
Referred pain is due to the fact that nerve signals
from several areas of the body may ‘‘feed’’ the same
nerve pathway leading to the spinal cord and brain.
Stimulus—A factor capable of eliciting a response
in a nerve.

through a thin tube called a laparascope, minimize
post-operative pain. Anesthesia techniques for surgeries also continuously improve. Some disease and
injuries are often unavoidable. However, pain from
some surgeries and other medical procedures and continuing pain are preventable through drug treatments
and alternative therapies.
Resources
PERIODICALS

‘‘Advances in Pain Management, New Focus Greatly Easing
Postoperative Care.’’ Medical Devices & Surgical
Technology Week September 26, 2004: 260.
Finn, Robert. ‘‘More than Half of Patients With Major
Depression Have Chronic Pain.’’ Family Practice News
October 15, 2004: 38.
‘‘New Guidelines Set for Better Pain Treatment.’’ Medical
Letter on the CDC & FDA September 5, 2004: 95.
ORGANIZATIONS

American Chronic Pain Association. P.O. Box 850,
Rocklin, CA 95677-0850. (916) 632-0922. <http://
members.tripod.com/~widdy/ACPA.html>.
American Pain Society. 4700 W. Lake Ave., Glenview, IL
60025. (847) 375-4715. <http://www.ampainsoc.org>.

Julia Barrett
Teresa G. Odle
and relaxation techniques such as yoga, hypnosis, and
meditation. Herbal therapies are gaining increased
recognition as viable options; for example, capsaicin,
the component that makes cayenne peppers spicy, is
used in ointments to relieve the joint pain associated
with arthritis. Contrast hydrotherapy can also be very
beneficial for pain relief.
Lifestyles can be changed to incorporate a healthier
diet and regular exercise. Regular exercise, aside from
relieving stress, has been shown to increase endorphins,
painkillers naturally produced in the body.

Prognosis
Successful pain treatment is highly dependent on
successful resolution of the pain’s cause. Acute pain
will stop when an injury heals or when an underlying
problem is treated successfully. Chronic pain and
abnormal pain are more difficult to treat, and it may
take longer to find a successful resolution. Some pain is
intractable and will require extreme measures for relief.

Prevention
Pain is generally preventable only to the degree
that the cause of the pain is preventable. For example,
improved surgical procedures, such as those done
GALE ENCYCLOPEDIA OF MEDICINE

Pain management
Definition
Pain management encompasses pharmacological,
nonpharmacological, and other approaches to prevent, reduce, or stop pain sensations.

Purpose
Pain serves as an alert to potential or actual
damage to the body. The definition for damage is
quite broad; pain can arise from injury as well as
disease. After the message is received and interpreted,
further pain can be counter-productive. Pain can have
a negative impact on a person’s quality of life and
impede recovery from illness or injury. Unrelieved
pain can become a syndrome in its own right and
cause a downward spiral in a person’s health and
outlook. Managing pain properly facilitates recovery,
prevents additional health complications, and improves
an individual’s quality of life.
2757

Pain management

KEY TERMS

Pain management

Description
What is pain?
Before considering pain management, a review of
pain definitions and mechanisms may be useful. Pain
is the means by which the peripheral nervous system
(PNS) warns the central nervous system (CNS) of
injury or potential injury to the body. The CNS
comprises the brain and spinal cord, and the PNS is
composed of the nerves that stem from and lead into
the CNS. The PNS includes all nerves throughout the
body except the brain and spinal cord.
A pain message is transmitted to the CNS by special PNS nerve cells called nociceptors. Nociceptors are
distributed throughout the body and respond to different stimuli depending on their location. For example,
nociceptors that extend from the skin are stimulated by
sensations such as pressure, temperature, and chemical
changes.
When a nociceptor is stimulated, neurotransmitters are released within the cell. Neurotransmitters
are chemicals found within the nervous system that
facilitate nerve cell communication. The nociceptor
transmits its signal to nerve cells within the spinal
cord, which conveys the pain message to the thalamus,
a specific region in the brain.
Once the brain has received and processed the
pain message and coordinated an appropriate
response, pain has served its purpose. The body uses
natural pain killers, called endorphins, that are meant
to derail further pain messages from the same source.
However, these natural pain killers may not adequately dampen a continuing pain message. Also,
depending on how the brain has processed the pain
information, certain hormones, such as prostaglandins, may be released. These hormones enhance the
pain message and play a role in immune system
responses to injury, such as inflammation. Certain
neurotransmitters, especially substance P and calcitonin gene-related peptide, actively enhance the pain
message at the injury site and within the spinal cord.
Pain is generally divided into two categories: acute
and chronic. Nociceptive pain, or the pain that is
transmitted by nociceptors, is typically called acute
pain. This kind of pain is associated with injury, headaches, disease, and many other conditions. It usually
resolves once the condition that caused it is resolved.
Following some disorders, pain does not resolve.
Even after healing or a cure has been achieved, the
brain continues to perceive pain. In this situation, the
pain may be considered chronic. The time limit used to
define chronic pain typically ranges from three to six
2758

months, although some healthcare professionals prefer a more flexible definition, and consider chronic
pain as pain that endures beyond a normal healing
time. The pain associated with cancer, persistent and
degenerative conditions, and neuropathy, or nerve
damage, is included in the chronic category. Also,
unremitting pain that lacks an identifiable physical
cause, such as the majority of cases of low back pain,
may be considered chronic. The underlying biochemistry of chronic pain appears to be different from
regular nociceptive pain.
Some researchers have said that uninterrupted
and unrelenting pain can induce changes in the spinal
cord. In the past, intractable pain has been treated by
severing a nerve’s connection to the CNS. However,
the lack of any sensory information being relayed by
that nerve can cause pain transmission in the spinal
cord to go into overdrive, as evidenced by the phantom limb pain experienced by amputees. Evidence is
accumulating that unrelenting pain or the complete
lack of nerve signals increases the number of pain
receptors in the spinal cord. Nerve cells in the spinal
cord may also begin secreting pain-amplifying neurotransmitters independent of actual pain signals from
the body. Immune chemicals, primarily cytokines,
may play a prominent role in such changes.
Scientists have long recognized a relationship
between depression and chronic pain. In 2004, a
survey of California adults diagnosed with major
depressive disorder revealed that more than one-half
of them also suffered from chronic pain.
Managing pain
Considering the different causes and types of pain,
as well as its nature and intensity, management can
require an interdisciplinary approach. The elements of
this approach include treating the underlying cause of
pain, pharmacological and nonpharmacological
therapies, and some invasive (surgical) procedures.
Treating the cause of pain underpins the idea of
managing it. Injuries are repaired, diseases are diagnosed, and certain encounters with pain can be anticipated and treated prophylactically (by prevention).
However, there are no guarantees of immediate relief
from pain. Recovery can be impeded by pain and
quality of life can be damaged. Therefore, pharmacological and other therapies have developed over time
to address these aspects of disease and injury.
PHARMACOLOGICAL
OPTIONS. Pain-relieving
drugs, otherwise called analgesics, include nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, narcotics, antidepressants, anticonvulsants, and

GALE ENCYCLOPEDIA OF MEDICINE

NSAIDs include aspirin, ibuprofen (Motrin,
Advil, Nuprin), naproxen sodium (Aleve), and ketoprofen (Orudis KT). These drugs are used to treat pain
from inflammation and work by blocking production
of pain-enhancing neurotransmitters, such as prostaglandins. Acetaminophen is also effective against
pain, but its ability to reduce inflammation is limited.
NSAIDs and acetaminophen are effective for most
forms of acute (sharp, but of a short course) pain, but
moderate and severe pain may require stronger medication. Narcotics handle intense pain effectively, and are
used for cancer pain and acute pain that does not
respond to NSAIDs and acetaminophen. Narcotics
are classified as either opiates or opioids, and are available only with a doctor’s prescription. Opiates include
morphine and codeine, which are derived from opium,
a substance naturally found in some poppy species.
Opioids are synthetic drugs based on the structure of
opium. This drug class includes drugs such as oxycodon, methadone, and meperidine (Demerol). In August
2004, the Drug Enforcement Administration (DEA)
issued new guidelines to help physicians prescribe
narcotics appropriately without fear of being arrested
for prescribing the drugs beyond the scope of their
medical practice. DEA is trying to work with physicians
to ensure that those who need to drugs receive them but
to ensure opioids are not abused.
Narcotics may be ineffective against some forms
of chronic pain, especially since changes in the spinal
cord may alter the usual pain signaling pathways. In
such situations, pain can be managed with the help of
with antidepressants and anticonvulsants, which are
also only available with a doctor’s prescription.
Although antidepressant drugs were developed to
treat depression, it has been discovered that they are
also effective in combating some chronic headaches,
cancer pain, and pain associated with nerve damage.
Antidepressants that have been shown to have analgesic (pain reducing) properties include amitriptyline
(Elavil), trazodone (Desyrel), and imipramine
(Tofranil). Anticonvulsant drugs share a similar background with antidepressants. Developed to treat epilepsy, certain anticonvulsants were found to relieve
pain as well. Drugs such as phenytoin (Dilantin) and
carbamazepine (Tegretol) are prescribed to treat the
pain associated with nerve damage.
GALE ENCYCLOPEDIA OF MEDICINE

Other prescription drugs are used to treat specific
types of pain or specific pain syndromes. For example,
corticosteroids are effective against pain caused
by inflammation and swelling, and sumatriptan
(Imitrex) was developed to treat migraine headaches.
Drug administration depends on the drug type
and the required dose. Some drugs are not absorbed
very well from the stomach and must be injected or
administered intravenously. Injections and intravenous administration may also be used when high
doses are needed or if an individual is nauseous.
Following surgery and other medical procedures,
patients may have the option of controlling the pain
medication themselves. By pressing a button, they can
release a set dose of medication into an intravenous
solution. This procedure has also been employed in
other situations requiring pain management. Another
mode of administration involves implanted catheters
that deliver pain medication directly to the spinal cord.
Delivering drugs in this way can reduce side effects
and increase the effectiveness of the drug.
NONPHARMACOLOGICAL OPTIONS. Pain treatment options that do not use drugs are often used as
adjuncts to, rather than replacements for, drug
therapy. One of the benefits of non-drug therapies is
that an individual can take a more active stance
against pain. Relaxation techniques, such as yoga
and meditation, are used to decrease muscle tension
and reduce stress. Tension and stress can also be
reduced through biofeedback, in which an individual
consciously attempts to modify skin temperature,
muscle tension, blood pressure, and heart rate.

Participating in normal activities and exercising
can also help control pain levels. Through physical
therapy, an individual learns beneficial exercises for
reducing stress, strengthening muscles, and staying fit.
Regular exercise has been linked to production of
endorphins, the body’s natural pain killers.
Acupuncture involves the insertion of small needles into the skin at key points. Acupressure uses these
same key points, but involves applying pressure rather
than inserting needles. Both of these methods may
work by prompting the body to release endorphins.
Applying heat or being massaged are very relaxing and
help reduce stress. Transcutaneous electrical nerve
stimulation (TENS) applies a small electric current to
certain parts of nerves, potentially interrupting pain
signals and inducing release of endorphins. To be
effective, use of TENS should be medically supervised.
INVASIVE PROCEDURES. There are three types of
invasive procedures that may be used to manage or
treat pain: anatomic, augmentative, and ablative.

2759

Pain management

others. NSAIDs and acetaminophen are available as
over-the-counter and prescription medications, and
are frequently the initial pharmacological treatment
for pain. These drugs can also be used as adjuncts
to the other drug therapies, which might require a
doctor’s prescription.

Pain management

These procedures involve surgery, and certain guidelines
should be followed before carrying out a procedure with
permanent effects. First, the cause of the pain must be
clearly identified. Next, surgery should be done only
if noninvasive procedures are ineffective. Third, any
psychological issues should be addressed. Finally,
there should be a reasonable expectation of success.
Anatomic procedures involve correcting the
injury or removing the cause of pain. Relatively
common anatomic procedures are decompression
surgeries, such as repairing a herniated disk in the
lower back or relieving the nerve compression related
to carpal tunnel syndrome. Another anatomic procedure is neurolysis, also called a nerve block, which
involves destroying a portion of a peripheral nerve.
Augmentative procedures include electrical stimulation or direct application of drugs to the nerves
that are transmitting the pain signals. Electrical
stimulation works on the same principle as TENS.
In this procedure, instead of applying the current
across the skin, electrodes are implanted to stimulate
peripheral nerves or nerves in the spinal cord.
Augmentative procedures also include implanted
drug-delivery systems. In these systems, catheters
are implanted in the spine to allow direct delivery of
drugs to the CNS.
Ablative procedures are characterized by severing
a nerve and disconnecting it from the CNS. However,
this method may not address potential alterations
within the spinal cord. These changes perpetuate
pain messages and do not cease even when the connection between the sensory nerve and the CNS is severed.
With growing understanding of neuropathic pain
and development of less invasive procedures, ablative
procedures are used less frequently. However, they do
have applications in select cases of peripheral neuropathy, cancer pain, and other disorders.

Preparation
Prior to beginning management, pain is thoroughly evaluated. Pain scales or questionnaires are
used to attach an objective measure to a subjective
experience. Objective measurements allow health
care workers a better understanding of the pain
being experienced by the patient. Evaluation also
includes physical examinations and diagnostic tests
to determine underlying causes. Some evaluations
require assessments from several viewpoints, including
neurology, psychiatry and psychology, and physical
therapy. If pain is due to a medical procedure, management consists of anticipating the type and intensity
of associated pain and managing it preemptively.
2760

KEY TERMS
Acute—Referring to pain in response to injury or
other stimulus that resolves when the injury heals
or the stimulus is removed.
Chronic—Referring to pain that endures beyond
the term of an injury or painful stimulus. Can also
refer to cancer pain, pain from a chronic or degenerative disease, and pain from an unidentified
cause.
CNS or central nervous system—The part of the
nervous system that includes the brain and the
spinal cord.
Iatrogenic—Resulting from the activity of the
physician.
Neuropathy—Nerve damage.
Neurotransmitter—Chemicals within the nervous
system that transmit information from or between
nerve cells.
Nociceptor—A nerve cell that is capable of sensing
pain and transmitting a pain signal.
Nonpharmacological—Referring to therapy that
does not involve drugs.
Pharmacological—Referring to therapy that relies
on drugs.
PNS or peripheral nervous system—Nerves that
are outside of the brain and spinal cord.
Stimulus—A factor capable of eliciting a response
in a nerve.

Risks
Owing to toxicity over the long term, some drugs
can only be used for acute pain or as adjuncts in
chronic pain management. NSAIDs have the wellknown side effect of causing gastrointestinal bleeding,
and long-term use of acetaminophen has been linked
to kidney and liver damage. Other drugs, especially
narcotics, have serious side effects, such as constipation, drowsiness, and nausea. Serious side effects can
also accompany pharmacological therapies; mood
swings, confusion, bone thinning, cataract formation,
increased blood pressure, and other problems may
discourage or prevent use of some analgesics.
Nonpharmacological therapies carry little or no
risk. However, it is advised that individuals recovering
from serious illness or injury consult with their health
care providers or physical therapists before making
use of adjunct therapies. Invasive procedures carry
GALE ENCYCLOPEDIA OF MEDICINE

A traditional concern about narcotics use has
been the risk of promoting addiction. As narcotic use
continues over time, the body becomes accustomed to
the drug and adjusts normal functions to accommodate to its presence. Therefore, to elicit the same level
of action, it is necessary to increase dosage over time.
As dosage increases, an individual may become physically dependent on narcotic drugs.
However, physical dependence is different from
psychological addiction. Physical dependence is characterized by discomfort if drug administration suddenly
stops, while psychological addiction is characterized by
an overpowering craving for the drug for reasons other
than pain relief. Psychological addiction is a very real
and necessary concern in some instances, but it should
not interfere with a genuine need for narcotic pain
relief. However, caution must be taken with people
with a history of addictive behavior.

Normal results
Effective application of pain management techniques reduces or eliminates acute or chronic pain. This
treatment can improve an individual’s quality of life
and aid in recovery from injury and disease.
Resources
PERIODICALS

Finn, Robert. ‘‘More than Half of Patients With Major
Depression Have Chronic Pain.’’ Family Practice News
October 15, 2004: 38.
‘‘New Guidelines Set for Better Pain Treatment.’’ Medical
Letter on the CDC & FDA September 5, 2004: 95.
ORGANIZATIONS

American Chronic Pain Association. P.O. Box 850, Rocklin,
CA 95677-0850. (916) 632-0922. <http://members.tripod.com/~widdy/ACPA.html>.
American Pain Society. 4700 West Lake Ave., Glenview, IL
60025. (847) 375-4715. <http://www.ampainsoc.org>.
National Chronic Pain Outreach Association, Inc. P.O. Box
274, Millboro, VA 24460- 9606. (540) 997-5004.

Julia Barrett
Teresa G. Odle

Pain relievers see Analgesics
Painful menstruation see Dysmenorrhea
Palliative cancer therapy see Cancer therapy,
palliative
GALE ENCYCLOPEDIA OF MEDICINE

Palpitations

risks similar to other surgical procedures, such as
infection, reaction to anesthesia, iatrogenic (injury as
a result of treatment) injury, and failure.

Palpitations
Definition
A sensation in which a person is aware of an
irregular, hard, or rapid heartbeat.

Description
Palpitations mean that the heart is not behaving
normally. It can appear to skip beats, beat rapidly,
beat irregularly, or thump in the chest. Although
palpitations are very common and often harmless,
they can be frightening to the person, who is usually
unaware of his or her heartbeat.
Palpitations can also be a sign of serious heart
trouble. Palpitations that are caused by certain types
of abnormal heart rhythms (arrhythmias) can be serious, and even fatal if left untreated. Recognizable
arrhythmias are present in a small number of patients
who have palpitations. Immediate medical attention
should be sought for palpitations that feel like a very
fast series of heartbeats, last more than two or three
minutes, and are unrelated to strenuous physical activity, obvious fright, or anger. Medical attention should
also be sought if palpitations are accompanied by
chest pain, dizziness, shortness of breath, or an overall
feeling of weakness.
Most people have experienced a skipped or missed
heartbeat, which is really an early beat and not a
skipped beat at all. After a premature heartbeat, the
heart rests for an instant then beats with extra force,
making the person feel as if the heart has skipped a beat.
This type of palpitation is nothing to worry about
unless it occurs frequently. Severe palpitations feel like
a thudding or fluttering sensation in the chest. After
chest pain, palpitations are the most common reason
that people are referred for cardiology evaluation.

Causes and symptoms
Palpitations can be caused by anxiety, arrhythmias, caffeine, certain medications, cocaine and other
amphetamines, emotional stress, overeating, panic,
somatization, and vigorous exercise. There may be
no other symptoms. But, anxiety, dizziness, shortness
of breath, and chest pain may be signs of more severe
arrhythmias.

Diagnosis
Palpitations are diagnosed through a medical history, a physical examination, an electrocardiogram
2761

Palpitations

(ECG), and screening for psychiatric disorders. It is
often difficult to distinguish palpitations from panic
disorder, a common problem in which the person
experiences frequent and unexplained ‘‘fight-orflight’’ responses, which is the body’s natural physical
reaction to extreme danger or physical exertion, but
without the obvious external stimulus.
To accurately diagnose palpitations, one of the
irregular heartbeats must be ‘‘captured’’ on an EKG,
which shows the heart’s activity. Electrodes covered
with a type of gel that conducts electrical impulses
are placed on the patient’s chest, arms, and legs.
These electrodes send impulses of the heart’s activity
to a recorder, which traces them on paper. This
electrocardiography test takes about 10 minutes and
is performed in a physician’s office or hospital.
Because the palpitations are unlikely to occur during
a standard EKG, Holter monitoring is often performed. In this procedure, the patient wears a small,
portable tape recorder that is attached to a belt or
shoulder strap and connected to electrode disks on
his or her chest. The Holter monitor records the
heart’s rhythm during normal activities. Some medical centers are now using event recorders that the
patient can carry for weeks or months. When the
palpitations occur, the patient presses a button on
the device, which captures the information about the
palpitations for physician evaluation. Later the
recording can be transmitted over the telephone line
for analysis.

KEY TERMS
Arrhythmia—Any variation from the normal heartbeat. Some arrhythmias are harmless, while others,
such as ventricular tachycardia, ventricular fibrillation, and ventricular standstill, can be fatal.
Somatization—Anxiety converted into physical
symptoms. Somatization is a sign of panic disorder.

(Crataegus laevigata) and motherwort (Leonurus
cardiaca) can help with palpitations. Homeopathic
remedies such as Lachesis, Digitalis, and Aconite
(Aconitum nnapellus) may be used to control palpitations but should be taken only when prescribed by
a homeopathic physician. Mind/body medicine
such as meditation and yoga can help the person
relax, eliminating or reducing palpitations caused
by anxiety or stress. Reducing or eliminating
tea, cola, coffee, and chocolate, and consuming
adequate amounts of the minerals calcium, magnesium, and potassium can help reduce or eliminate
palpitations.

Prognosis
Most palpitations are harmless, but some can be a
sign of heart trouble, which could be fatal if left
untreated.

Treatment
Most palpitations require no treatment. Persistent
palpitations can be treated with small doses of a beta
blocker. Beta blockers are drugs that tend to lower
blood pressure. They slow the heart rate and decrease
the force with which the heart pumps. If the cause of
the palpitations is determined to be an arrhythmia,
medical or surgical treatment may be prescribed,
although surgery is rarely needed.

Alternative treatment
Alternative treatments for palpitations should
be used only as a complement to traditional medicine.
Alternative treatments include: aromatherapy,
Chinese herbs, herbal therapies, homeopathic medicine, exercise, mind/body medicine, and diet and
nutrition. In aromatherapy, adding citrus oils to
bath water may help with minor palpitations. Some
Chinese herbs can also help, but others can worsen
arrhythmias, so a qualified herbalist should be
consulted. Herbal therapies such as hawthorn
2762

Prevention
Palpitations not caused by arrhythmias can be
prevented by reducing or eliminating anxiety and
emotional stress, and reducing or eliminating consumption of tea, cola, coffee, and chocolate. Exercise
can also help, but a treadmill stress test performed by a
physician should be considered first to make sure the
exercise is safe.
Resources
PERIODICALS

Mayou, Richard. ‘‘Chest Pain, Palpitations, and
Panic.’’ Journal of Psychosomatic Research 44
(1998): 53-70.

Lori De Milto

Panax quinquefolius see Ginseng
Pancreas removal see Pancreatectomy
GALE ENCYCLOPEDIA OF MEDICINE

Pancreas transplantation

Pancreas transplantation

National Transplant Waiting List By Organ Type (June 2000)

Definition
Pancreas transplantation is a surgical procedure
in which a diseased pancreas is replaced with a healthy
pancreas that has been obtained immediately after
death from an immunologically compatible donor.

Purpose
The pancreas secretes insulin to regulate glucose
(sugar) metabolism. Failure to regulate glucose levels
leads to diabetes. Over one million patients in the
United States have insulin dependent (type I) diabetes
mellitus. Successful pancreas transplantation
allows the body to make and secrete its own insulin,
and establishes insulin independence for these
patients.
Pancreas transplantation is major surgery that
requires suppression of the immune system to prevent
the body from rejecting the transplanted pancreas.
Immunosuppressive drugs have serious side effects.
Because of these side effects, in 1996, 85% of pancreas transplants were performed simultaneously
with kidney transplants, 10% after a kidney transplant, and only 5% were performed as a pancreas
transplant alone.
The rationale for this is that patients will already
be receiving immunosuppressive treatments for the
kidney transplant, so they might as well receive the
benefit of a pancreas transplant as well. Patients considering pancreas transplantation alone must decide
with their doctors whether life-long treatment with
immunosuppressive drugs is preferable to life-long
insulin dependence.

Organ Needed

Number Waiting

Kidney
Liver
Heart
Lung
Kidney-Pancreas
Pancreas
Heart-Lung
Intestine

48,349
15,987
4,139
3,695
2,437
942
212
137

injections are usually not considered for pancreas
transplants.

Description
Once a donor pancreas is located, the patient is
prepared for surgery. Since only about 1,000 pancreas
transplants are performed each year in the United
States, the operation usually occurs at a hospital
where surgeons have special expertise in the procedure.
The surgeon makes an incision under the ribs and
locates the pancreas and duodenum. The pancreas and
duodenum (part of the small intestine) are removed.
The new pancreas and duodenum are then connected
to the patient’s blood vessels.
Replacing the duodenum allows the pancreas to
drain into the gastrointestinal system. The transplant
can also be done creating a bladder drainage. Bladder
drainage makes it easier to monitor organ rejection.
Once the new pancreas is in place, the abdomen and
skin are closed. This surgery is often done at the same
time as kidney transplant surgery.

The best candidates for pancreas transplantation
are:

Preparation



between the ages of 20–40



those who have extreme difficulty regulating their
glucose levels



those who have few secondary complications of
diabetes



those who are in good cardiovascular health.

Precautions
Many people with diabetes are not good candidates for a pancreas transplant. Others do not have
tissue compatibility with the donor organ. People who
are successfully controlling their diabetes with insulin
GALE ENCYCLOPEDIA OF MEDICINE

After the patient and doctor have decided on a
pancreas transplant, a complete immunological study
is done to match the patient to a donor. All body
functions are evaluated. The timing of surgery
depends on the availability of a donated organ.

Aftercare
Patients receiving a pancreas transplantation are
monitored closely for organ rejection, and all vital
body functions are monitored also. The average
hospital stay is three weeks. It takes about six months
to recover from surgery. Patients will take immunosuppressive drugs for the rest of their lives.
2763

Pancreas transplantation
A surgeon harvests the islets of Langerhans from a donor pancreas. (Photograph by Daniel Portnoy. AP/Wide World Photo.
Reproduced by permission.)

KEY TERMS
Duodenum—The section of the small intestine
immediately after the stomach.

Risks
Diabetes and poor kidney function greatly increase
the risk of complications from anesthesia during
surgery. Organ rejection, excessive bleeding, and infection are other major risks associated with this surgery.

Normal results
During a nine year period from 1987 to 1996, the
patient survival rate for all types of pancreas
2764

transplants (with or without associated kidney transplant) was 92% after one year and 86% after three
years. In a successful transplant, the pancreas begins
producing insulin, bringing the regulation of glucose
back under normal body control. Natural availability
of insulin prevents the development of additional
damage to the kidneys and blindness associated
with diabetes. Many patients report an improved
quality of life.
Resources
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383.
<http://www.diabetes.org>.

Tish Davidson, A.M.
GALE ENCYCLOPEDIA OF MEDICINE

Pancreatectomy
Definition
Pancreatectomy is the surgical removal of the
pancreas. Pancreatectomy may be total, in which
case the whole organ is removed, or partial, referring
to the removal of part of the pancreas.

Purpose
Pancreatectomy is the most effective treatment
for cancer of the pancreas, an abdominal organ that
secretes digestive enzymes, insulin, and other hormones.
The thickest part of the pancreas near the duodenum
(small intestine) is called the head, the middle part is
called the body, and the thinnest part adjacent to the
spleen is called the tail.
While surgical removal of tumors in the pancreas
is preferred, it is only possible in the 10-15% of
patients who are diagnosed early enough for a potential cure. Patients who are considered suitable for
surgery usually have small tumors in the head of the
pancreas (close to the duodenum, or first part of the
small intestine), have jaundice as their initial symptom,
and have no evidence of metastatic disease (spread of
cancer to other sites).
Pancreatectomy is sometimes necessary when
the pancreas has been severely injured by trauma,
especially injury to the body and tail of the pancreas.
While such surgery removes normal pancreatic
tissue as well, the long-term consequences of this
surgery are minimal, with virtually no effects on the
production of insulin, digestive enzymes, and other
hormones.
Chronic pancreatitis is another condition for
which pancreatectomy is occasionally performed.
Chronic pancreatitis—or continuing inflammation of
the pancreas that results in permanent damage to this
organ—can develop from long-standing, recurring
episodes of acute (periodic) pancreatitis. This painful
condition usually results from alcohol abuse or
the presence of gallstones. In most patients with
alcohol-induced disease, the pancreas is widely
involved, therefore, surgical correction is almost
impossible.

Precautions
Pancreatectomy is only performed when surgery
provides a clear benefit. Patients who have tumors
that are obviously not operable should be carefully
excluded from consideration.
GALE ENCYCLOPEDIA OF MEDICINE

Pancreatectomy sometimes entails removal of
the entire pancreas, called a total pancreatectomy,
but more often involves removal of part of the
pancreas, which is called a subtotal pancreatectomy,
or distal pancreatectomy, when the body and tail of
the pancreas are removed. When the duodenum is
removed along with all or part of the pancreas, the
procedure is called a pancreaticoduodenectomy,
which surgeons sometimes refer to as ‘‘Whipple’s
procedure.’’ Pancreaticoduodenectomy is being
used increasingly for treatment of a variety of malignant and benign diseases of the pancreas.
Regional lymph nodes are usually removed during pancreaticoduodenectomy. In distal pancreatectomy, the spleen may also be removed.

Preparation
Patients with symptoms of a pancreatic disorder
usually undergo a number of tests before surgery is
even considered. These can include ultrasonography,
x-ray examinations, computed tomography scans (CT
scan), and endoscopic retrograde cholangiopancreatography (ERCP), an x-ray imaging technique. Tests
may also include angiography, an x-ray technique
for visualizing the arteries feeding the pancreas, and
needle aspiration cytology, in which cells are drawn
from areas suspected to contain cancer. Such tests aid
in the diagnosis of the pancreatic disorder and in the
planning of the operation.
Since many patients with pancreatic cancer are
undernourished, appropriate nutritional support,
sometimes by tube feedings, may be required prior to
surgery.
Some patients with pancreatic cancer deemed suitable for pancreatectomy will undergo chemotherapy
and/or radiation therapy. This treatment is aimed at
shrinking the tumor, which will improve the chances
for successful surgical removal. Sometimes, patients
who are not initially considered surgical candidates
may respond so well to chemoradiation that surgical
treatment becomes possible. Radiation therapy may
also be applied during the surgery (intraoperatively)
to improve the patient’s chances of survival, but this
treatment is not yet in routine use. Some studies have
shown that intraoperative radiation therapy extends
survival by several months.
Patients undergoing distal pancreatectomy that
involves removal of the spleen may receive preoperative medication to decrease the risk of infection.
2765

Pancreatectomy

Description

Pancreatectomy

Aftercare
Pancreatectomy is major surgery. Therefore,
extended hospitalization is usually required. Some
studies report an average hospital stay of about two
weeks.
Some cancer patients may also receive combined
chemotherapy and radiation therapy after surgery.
This additional treatment has been clearly shown to
enhance survival from pancreatic cancer.
Removal of all or part of the pancreas can lead to
a condition called pancreatic insufficiency, in which
food cannot be normally processed by the body, and
insulin secretion may be inadequate. These conditions
can be treated with pancreatic enzyme replacement
therapy, to supply digestive enzymes, and insulin
injections, to supply insulin.

Risks
The mortality rate for pancreatectomy has
improved in recent years to 5–10%, depending on
the extent of the surgery and the experience of the
surgeon. A study of 650 patients at Johns Hopkins
Medical Institution, Baltimore, found that only nine
patients, or 1.4%, died from complications related to
surgery.
There is still, however, a fairly high risk of complications following any form of pancreatectomy. The
Johns Hopkins study documented complications in
41% of cases. The most devastating complication is
postoperative bleeding, which increases the mortality
risk to 20-50%. In cases of postoperative bleeding, the
patient may be returned to surgery to find the source
of hemorrhage, or may undergo other procedures to
stop the bleeding.
One of the most common complications from a
pancreaticoduodenectomy is delayed gastric emptying, a condition in which food and liquids are slow to
leave the stomach. This complication occurred in 19%
of patients in the Johns Hopkins study. To manage
this problem, many surgeons insert feeding tubes at
the original operation site, through which nutrients
can be fed directly into the patient’s intestines. This
procedure, called enteral nutrition, maintains the
patient’s nutrition if the stomach is slow to recover
normal function. Certain medications, called promotility agents, can help move the nutritional contents
through the gastrointestinal tract.
The other most common complication is pancreatic anastomotic leak. This is a leak in the connection
that the surgeon makes between the remainder of the
pancreas and the other structures in the abdomen.
2766

KEY TERMS
Chemotherapy—A treatment of the cancer with
synthetic drugs that destroy the tumor either by
inhibiting the growth of the cancerous cells or by
killing the cancer cells.
Computed tomography (CT) scan—A medical procedure where a series of x rays are taken and put
together by a computer in order to form detailed
pictures of areas inside the body.
Magnetic resonance imaging (MRI)—A medical
procedure used for diagnostic purposes where pictures of areas inside the body can be created using a
magnet linked to a computer.
Pancreas—A large gland located on the back wall
of the abdomen, extending from the duodenum
(first part of the small intestine) to the spleen. The
pancreas produces enzymes essential for digestion,
and the hormones insulin and glucagon, which
play a role in diabetes.
Pancreaticoduodenectomy—Removal of all or
part of the pancreas along with the duodenum.
Also known as ‘‘Whipple’s procedure’’ or
‘‘Whipple’s operation.’’
Pancreatitis—Inflammation of the pancreas, either
acute (sudden and episodic) or chronic, usually
caused by excessive alcohol intake or gallbladder
disease.
Radiation therapy—A treatment using high energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Ultrasonogram—A procedure where highfrequency sound waves that cannot be heard by
human ears are bounced off internal organs and
tissues. These sound waves produce a pattern of
echoes which are then used by the computer to
create sonograms or pictures of areas inside the body.

Most surgeons handle the potential for this problem
by assuring that there will be adequate drainage from
the surgical site.

Normal results
Unfortunately, pancreatic cancer is the most
lethal form of gastrointestinal malignancy. However,
for a highly selective group of patients, pancreatectomy offers a chance for cure, especially when
performed by experienced surgeons. The overall fiveyear survival rate for patients who undergo
GALE ENCYCLOPEDIA OF MEDICINE

After total pancreatectomy, the body loses the
ability to secrete insulin, enzymes, and other substances, therefore, certain medications will be required
to compensate for this. In some cases of pancreatic
disease, the pancreas ceases to function normally, then
total pancreatectomy may be preferable to other less
radical forms of the operation.
When pancreatectomy is performed for chronic
pancreatitis, the majority of patients obtain some
relief from pain. Some studies report that one half to
three quarters of patients become free of pain.
Resources
BOOKS

Bastidas, J. Augusto, and John E. Niederhuber. ‘‘The
Pancreas.’’ In Fundamentals of Surgery, edited by John
E. Niederhuber. Stamford: Appleton & Lange, 1998.

Caroline A. Helwick

Pancreatic cancer, endocrine
Definition
Endocrine pancreatic cancer is a disease in which
cancerous cells originate within the tissues of the
pancreas that produce hormones.

Description
The pancreas is a 6-8 in (15-20 cm) long, slippershaped gland located in the abdomen. It lies behind
the stomach, within a loop formed by the small intestine. Other nearby organs include the gallbladder,
spleen, and liver. The pancreas has a wide end
(head), a narrow end (tail), and a middle section
(body). A healthy pancreas is important for normal
food digestion and plays a critical role in the body’s
metabolic processes. The pancreas has two main functions, each performed by distinct types of tissue. The
exocrine tissue secretes fluids into the other organs of
the digestive system, while the endocrine tissue
GALE ENCYCLOPEDIA OF MEDICINE

secretes substances that are circulated in the bloodstream. The exocrine pancreas makes up the vast
majority of the gland; it produces pancreatic juices
containing enzymes that help break down proteins
and fatty food. The endocrine tissue of the pancreas
makes up only 2% of the gland’s total mass. It consists
of small patches of cells that produce hormones (like
insulin) that control how the body stores and uses
nutrients. These patches are called islets (islands) of
Langerhans or islet cells and are interspersed evenly
throughout the pancreas. Each islet contains approximately 1,000 endocrine cells and a dense network of
capillaries (tiny blood vessels), which allows immediate entry of hormones into the circulatory system.
Pancreatic tumors are classified as either exocrine
or endocrine tumors depending on which type of tissue
they arise from within the gland. Endocrine tumors
of the pancreas are very rare, accounting for only 5%
of all pancreatic cancers. The majority of endocrine
pancreatic tumors are functional adenocarcinomas
that overproduce a specific hormone. There are
several types of islet cells and each produces its own
hormone or peptide (small protein molecule).
Functional endocrine tumors are named after the
hormone they secrete. Insulinoma is the most common
tumor of the endocrine pancreas. Patients with this
disease usually develop hypoglycemia due to increased
insulin production that leads to abnormally low blood
sugar levels. Gastrinoma, a disease in which gastrin
(hormone that stimulates stomach acid production)
is overproduced, causes multiple ulcers in the upper
gastrointestinal (GI) tract. Gastrinoma was first
described in patients with a rare form of severe peptic
ulcer disease known as Zollinger-Ellison syndrome
(ZES). The less common glucagonoma causes mild
diabetes due to excess glucagon (hormone that stimulates glucose production) secretion. Other rare islet
cell tumors include vipoma (vasoactive intestinal
peptide) and somatostatinoma. Nonfunctional pancreatic endocrine tumors are not associated with an
excess production of any hormone and can be difficult
to distinguish from exocrine pancreatic cancer.
Cancers of the endocrine pancreas are relatively
slow-growing compared to the more common ductal
adenocarcinomas of the exocrine pancreas.
Between one and four cases of insulinoma occur
per million people per year, and 90% of these tumors
are benign. They occur mostly between the ages of 50
and 60 and affect men and women equally. Less than
three cases of gastrinoma per million people are diagnosed each year, but it is the most common functional
islet cell tumor in patients with multiple endocrine
tumors, a condition known as multiple endocrine
2767

Pancreatic cancer, endocrine

pancreatectomy for pancreatic cancer is about 10%;
patients who undergo pancreaticoduodenectomy have
a 4–5% survival at five years. The risk for tumor
recurrence is thought to be unaffected by whether the
patient undergoes a total pancreatectomy or a pancreaticoduodenectomy, but is increased when the
tumor is larger than 3 cm and the cancer has spread
to the lymph nodes or surrounding tissue.

Pancreatic cancer, endocrine

neoplasia (MEN) syndrome. Vipoma and glucagonoma are even rarer and they occur more frequently
in women. Somatostatinoma is exceedingly uncommon, and less than 100 cases have been reported
worldwide. Nonfunctional islet cell cancers account
for approximately one-third of all cancers of the
endocrine pancreas, and the majority of these are
malignant.

Causes and symptoms
There are no known causes of islet cell cancer, but
a small percentage of cases occur due to hereditary
syndromes such as MEN. This is a condition that
frequently causes more than one tumor in several
endocrine glands, such as the parathyroid and pituitary, in addition to the islet cells of the pancreas.
Twenty-five percent of gastrinomas and less than
10% of insulinomas occur in MEN patients. Von
Hippel-Lindau (VHL) syndrome is another genetic
disorder that causes multiple tumors, and 10–15% of
VHL patients will develop islet cell cancer.
Symptoms vary among the different islet cell
cancer types. Insulinoma causes repeated episodes of
hypoglycemia, sweating, and tremors, while patients
with gastrinoma have inflammation of the esophagus,
epigastric pain, multiple ulcers, and possibly diarrhea.
Symptoms of glucagonoma include a distinctive
skin rash, inflammation of the stomach, glucose intolerance, weight loss, weakness, and anemia (less common). Patients with vipoma have episodes of profuse,
watery diarrhea, even after fasting. Somatostatinoma
causes mild diabetes, diarrhea/steatorrhea (fatty
stools), weight loss, and gallbladder disease. Nonfunctional endocrine tumors frequently produce the
same symptoms as cancer of the exocrine pancreas
such as abdominal pain, jaundice, and weight loss.

Diagnosis
A thorough physical exam is usually performed
when a patient presents with the above symptoms,
however, functional endocrine tumors of the pancreas
tend to be small and are not detected by palpating the
abdomen. Once other illnesses such as infection are
ruled out, the doctor will order a series of blood and
urine tests. The functional endocrine tumors can be
identified through increased levels of hormone in the
bloodstream.
Functional endocrine tumors can occur in multiple sites in the pancreas and are often small (less than
1 cm), making them difficult to diagnose. Nonfunctional tumors tend to be larger, which makes
2768

them difficult to distinguish from tumors of the
exocrine pancreas. Methods such as computed tomography (CT) scan and magnetic resonance imaging
(MRI) are used to take pictures of the internal organs
and allow the doctor to determine whether a tumor is
present. Somatostatin receptor scintigraphy (trade
name OctreoScan) is an imaging system used to localize endocrine tumors, especially gastrinomas and
somatostatinomas. Endoscopic ultrasound (EUS) is
a more sensitive technique that may be used if a CT
scan fails to detect a tumor. Endocrine tumors usually
have many blood vessels, so angiography may be
useful in the doctor’s assessment and staging of the
tumor. Surgical exploration is sometimes necessary
in order to locate very small tumors that occur in
multiple sites. These techniques also help the doctor
evaluate how far the tumor has spread. A biopsy can
be taken to confirm diagnosis, but more often, doctors
look at the size and local invasion of the tumor in
order to plan a treatment strategy.

Treatment
Staging
The staging system for islet cell cancer is still
evolving, but the tumors typically fall into three categories: cancers that arise in one location within the
pancreas, cancers that arise in several locations within
the pancreas, and cancers that have spread to nearby
lymph nodes or to other organs in the body.
Surgery is the only curative method for islet cell
cancers, and studies have shown that an aggressive
surgical approach can improve survival and alleviate
symptoms of the disease. As with most forms of cancer, the earlier it is diagnosed, the greater the chance
for survival. With the exception of insulinoma, the
majority of islet cell tumors are malignant at the time
of diagnosis, and more than half are metastatic.
However, surgery and chemotherapy have been
shown to improve the outcome of patients even if
they have metastatic disease. Surgery may include
partial or total removal of the pancreas, and in
patients with gastrinoma, the stomach may be
removed as well. Streptozotocin, doxorubicin, and
5-fluorouracil (5-FU) are chemotherapeutic agents
commonly used in the treatment of islet cell cancer.
Patients may experience nausea and vomiting as well
as kidney toxicity from streptozotocin, and bone
marrow suppression from doxorubicin. Hormone
therapy is used to relieve the symptoms of functional
tumors by inhibiting excess hormone production.
Other techniques may be used to block blood flow to
the liver in an attempt to kill the cancer cells that have
GALE ENCYCLOPEDIA OF MEDICINE

Adenocarcinoma—A malignant tumor that arises
within the tissues of a gland and retains its glandular structure.
Angiography—Diagnostic technique used to study
blood vessels in a tumor.
Biopsy—Removal and microscopic examination of
cells to determine whether they are cancerous.
Chemotherapy—Drug treatment administered to
kill cancerous cells.
Endocrine—Refers to glands that secrete hormones
circulated in the bloodstream.
Endoscopic ultrasonography (EUS)—Diagnostic
imaging technique where an ultrasound probe is
inserted down a patient’s throat to determine if a
tumor is present.
Gastrinoma—Tumor that arises from the gastrinproducing cells in the pancreas.
Insulinoma—Tumor that arises from the insulinproducing cells in the pancreas.
Islets of Langerhans—Clusters of cells in the pancreas that make up the endocrine tissue.

PERIODICALS

Anderson, M.A., et. al. ‘‘Endoscopic Ultrasound is
HighlyAccurate and Directs Management of Patients
With Neuroendocrine Tumors of the Pancreas.’’
American Journal of Gastroenterology 95, no. 9
(September 2000): 2271–7.
Hellman, Per, et. al. ‘‘Surgical Strategy for Large or
Malignant Endocrine Pancreatic Tumors.’’ World
Journal of Surgery 24 (2000): 1353–60.
ORGANIZATIONS

National Cancer Institute. 9000 Rockville Pike, Bldg. 31,
Rm.10A16, Bethesda, MD, 20892. (800) 422-6237.
<http://www.nci.nih.gov>.
National Familial Pancreas Tumor Registry. The Johns
Hopkins Hospital. 600 North Wolfe St., Baltimore,
MD 21287-6417. (410) 377-7450.
National Organization for Rare Disorders. 100 Route 37,
PO Box 8923, New Fairfield, CT 06812. (203) 746-6518.
<http://www.nord-rdb.com/~orphan>.
OTHER

‘‘Islet Cell Carcinoma.’’ CancerNetPDQ May 2001. [cited
July 19, 2001]. <http://www.cancernet.nci.nih.gov>.
Pancreatic Cancer Home Page. Johns Hopkins Medical
Institutions. July 19, 2001. <http://
www.path.jhu.edu/pancreas>.

Elizabeth Pulcini, M.Sc.
spread there. Abdominal pain, nausea, vomiting and
fever may result from this type of treatment. Radiation
has little if any role in the treatment of islet cell cancer.

Prognosis
Islet cell cancers overall have a more favorable
prognosis than cancers of the exocrine pancreas, and
the median survival from diagnosis is three and a half
years. This is mainly due to their slow-growing nature.
Insulinomas have a five-year survival rate of 80%
and gastrinomas have 65%. When malignant, islet
cell cancers do not generally respond well to chemotherapy, and the treatment is mainly palliative. Most
patients with metastasis do not survive five years. Islet
cell cancer tends to spread to the surrounding lymph
nodes, stomach, small intestine, and liver.

Prevention
There are no known risk factors associated with
sporadic islet cell cancer. Therefore, it is not clear how
to prevent its occurrence. Individuals with MEN syndrome or VHL, however, have a genetic predisposition
to developing islet cell cancer and should be screened
regularly in an effort to catch the disease early.
GALE ENCYCLOPEDIA OF MEDICINE

Pancreatic cancer, exocrine
Definition
Exocrine pancreatic cancer is a disease in which
cancerous cells originate within the tissues of the
pancreas that produce digestive juices.

Description
The pancreas is a 6-8 in (15-20 cm) long, slippershaped gland located in the abdomen. It lies behind
the stomach, within a loop formed by the small intestine. Other nearby organs include the gallbladder,
spleen, and liver. The pancreas has a wide end
(head), a narrow end (tail), and a middle section
(body). A healthy pancreas is important for normal
food digestion and also plays a critical role in the
body’s metabolic processes. The pancreas has two
main functions, and each are performed by distinct
types of tissue. The exocrine tissue makes up the vast
majority of the gland and secretes fluids into the other
2769

Pancreatic cancer, exocrine

Resources

KEY TERMS

Pancreatic cancer, exocrine

organs of the digestive system. The endocrine tissue
secretes hormones (like insulin) that are circulated in
the bloodstream, and these substances control how the
body stores and uses nutrients. The exocrine tissue of
the pancreas, comprised mostly of acinar cells and
ductal cells, produces pancreatic (digestive) juices.
These juices contain several enzymes that help break
down proteins and fatty foods. The exocrine pancreas
forms an intricate system of channels or ducts, which
are tubular structures that carry pancreatic juices to
the small intestine where they are used for digestion.
Pancreatic tumors are classified as either exocrine
or endocrine tumors depending on which type of tissue
they arise from within the gland. Ninety-five percent
of pancreatic cancers occur in the tissues of the
exocrine pancreas. Ductal adenocarcinomas arise in
the cells that line the ducts of the exocrine pancreas
and account for 80% to 90% of all tumors of the
pancreas. Unless specified, nearly all reports on
pancreatic cancer refer to ductal adenocarcinomas.
Less common types of pancreatic exocrine tumors
include acinar cell carcinoma, cystic tumors that are
typically benign but may become cancerous, and
papillary tumors that grow within the pancreatic
ducts. Pancreatoblastoma is a very rare disease that
primarily affects young children. Two-thirds of pancreatic tumors occur in the head of the pancreas, and
tumor growth in this area can lead to the obstruction
of the nearby common bile duct that empties bile fluid
into the small intestine. When bile cannot be passed
into the intestine, patients may develop yellowing of
the skin and eyes (jaundice) due to the buildup of
bilirubin (a component of bile) in the bloodstream.
Tumor blockage of bile or pancreatic ducts may also
cause digestive problems since these fluids contain
critical enzymes in the digestive process. Depending
on their size, pancreatic tumors may cause abdominal
pain by pressing on the surrounding nerves. Because
of its location deep within the abdomen, pancreatic
cancer often remains undetected until it has spread to
other organs such as the liver or lung. Pancreatic
cancer tends to rapidly spread to other organs, even
when the primary (original) tumor is relatively small.
Though pancreatic cancer accounts for only 3%
of all cancers, it is the fifth most frequent cause of
cancer deaths. In 2001, an estimated 29,200 new
cases of pancreatic cancer will be diagnosed in the
United States. Pancreatic cancer is primarily a disease
associated with advanced age, with 80% of cases
occurring between the ages of 60 and 80. Men are
almost twice as likely to develop this disease than
women. Countries with the highest frequencies of pancreatic cancer include the United States, New Zealand,
2770

Western European nations, and Scandinavia. The
lowest occurrences of the disease are reported in
India, Kuwait and Singapore. African Americans
have the highest incidence of pancreatic cancer of
any ethnic group worldwide. Whether this difference
is due to diet or environmental factors remains
unclear.

Causes and symptoms
Although the exact cause for pancreatic cancer is
not known, several risk factors have been shown to
increase susceptibility to this particular cancer, the
greatest of which is cigarette smoking. Approximately
one-third of pancreatic cancer cases occur among
smokers. People who have diabetes develop pancreatic
cancer twice as often as non-diabetics. Numerous
studies suggest that a family history of pancreatic
cancer is another strong risk factor for developing the
disease, particularly if two or more relatives in the
immediate family have the disease. Other risk factors
include chronic (long-term) inflammation of the pancreas (pancreatitis), diets high in fat, and occupational
exposure to certain chemicals such as petroleum.
Pancreatic cancer often does not produce symptoms until it reaches an advanced stage. Patients may
then present with the following signs and symptoms:



upper abdominal and/or back pain



jaundice



weight loss



loss of appetite



diarrhea



weakness



nausea

These symptoms may also be caused by other illnesses; therefore, it is important to consult a doctor for
an accurate diagnosis.

Diagnosis
Pancreatic cancer is difficult to diagnose, especially in the absence of symptoms, and there is no
current screening method for early detection. The
most sophisticated techniques available often do not
detect very small tumors that are localized (have not
begun to spread). At advanced stages where patients
show symptoms, a number of tests may be performed
to confirm diagnosis and to assess the stage of the
disease. Approximately half of all pancreatic cancers
GALE ENCYCLOPEDIA OF MEDICINE

The first step in diagnosing pancreatic cancer is a
thorough medical history and complete physical
examination. The abdomen will be palpated to check
for fluid accumulation, lumps, or masses. If there are
signs of jaundice, blood tests will be performed to rule
out the possibility of liver diseases such as hepatitis.
Urine and stool tests may be performed as well.
Non-invasive imaging tools such as computed
tomography (CT) scans and magnetic resonance imaging (MRI) can be used to produce detailed pictures of
the internal organs. CT is the tool most often used to
diagnose pancreatic cancer, as it allows the doctor to
determine if the tumor can be removed by surgery or
not. It is also useful in staging a tumor by showing the
extent to which the tumor has spread. During a CT
scan, patients receive an intravenous injection of a
contrast dye so the organs can be visualized more
clearly. MRI may be performed instead of CT if a
patient has an allergy to the CT contrast dye. In
some cases where the tumor is impinging on blood
vessels or nearby ducts, MRI may be used to generate
an image of the pancreatic ducts.
If the doctor suspects pancreatic cancer and no
visible masses are seen with a CT scan, a patient may
undergo a combination of invasive tests to confirm
the presence of a pancreatic tumor. Endoscopic
ultrasound (EUS) involves the use of an ultrasound
probe at the end of a long, flexible tube that is passed
down the patient’s throat and into the stomach.
This instrument can detect a tumor mass through
high frequency sound waves and echoes. EUS can
be accompanied by fine needle aspiration (FNA),
where a long needle, guided by the ultrasound, is
inserted into the tumor mass in order to take a biopsy
sample. Endoscopic retrograde cholangiopancreatography (ERCP) is a technique often used in patients
with severe jaundice because it enables the doctor
to relieve blockage of the pancreatic ducts. The
doctor, guided by endoscopy and x rays, inserts a
small metal or plastic stent into the duct to keep it
open. During ERCP, a biopsy can be done by collecting cells from the pancreas with a small brush.
The cells are then examined under the microscope by
a pathologist, who determines the presence of any
cancerous cells.
In some cases, a biopsy may be performed during
a type of surgery called laparoscopy, which is done
under general anesthesia. Doctors insert a small camera and instruments into the abdomen after a minor
incision is made. Tissue samples are removed for
GALE ENCYCLOPEDIA OF MEDICINE

examination under the microscope. This procedure
allows a doctor to determine the extent to which the
disease has spread and decide if the tumor can be
removed by further surgery.
An angiography is a type of test that studies the
blood vessels in and around the pancreas. This test
may be done before surgery so that the doctor can
determine the extent to which the tumor invades and
interacts with the blood vessels within the pancreas.
The test requires local anesthesia and a catheter is
inserted into the patient’s upper thigh. A dye is then
injected into blood vessels that lead into the pancreas,
and x rays are taken.
As of April 2001, doctors at major cancer research
institutions such as Memorial Sloan-Kettering Cancer
Center in New York are investigating CT angiography, an imaging technique that is less invasive than
angiography alone. CT angiography is similar to a
standard CT scan, but allows doctors to take a series
of pictures of the blood vessels that support tumor
growth. A dye is injected as in a CT scan (but at
rapid intervals) and no catheter or sedation is required.
A computer generates 3D images from the pictures
that are taken, and the information is gathered by
the surgical team who will develop an appropriate
strategy if the patient’s disease can be operated on.

Treatment
Staging
After cancer of the pancreas has been diagnosed,
doctors typically use a TNM staging system to classify
the tumor based on its size and the degree to which it
has spread to other areas in the body. T indicates the
size and local advancement of the primary tumor.
Since cancers often invade the lymphatic system
before spreading to other organs, regional lymph
node involvement (N) is an important factor in staging. M indicates whether the tumor has metastasized
(spread) to distant organs. In stage I, the tumor is
localized to the pancreas and has not spread to surrounding lymph nodes or other organs. Stage II pancreatic cancer has spread to nearby organs such as the
small intestine or bile duct, but not the surrounding
lymph nodes. Stage III indicates lymph node involvement, whether the cancer has spread to nearby organs
or not. Stage IVA pancreatic cancer has spread to
organs near the pancreas such as the stomach, spleen,
or colon. Stage IVB is a cancer that has spread to
distant sites (liver, lung). If pancreatic cancer has
been treated with success and then appears again in
the pancreas or in other organs, it is referred to as
recurrent disease.
2771

Pancreatic cancer, exocrine

are metastatic (have spread to other sites) at the time
of diagnosis.

Pancreatic cancer, exocrine

Treatment of pancreatic cancer will depend on
several factors, including the stage of the disease and
the patient’s age and overall health status. A combination of therapies is often employed in the treatment
of this disease to improve the patient’s chances for
survival. Surgery is used whenever possible and is the
only means by which cancer of the pancreas can be
cured. However, less than 15% of pancreatic tumors
can be removed by surgery. By the time the disease is
diagnosed (usually at stage III), therapies such as
radiation and chemotherapy or both are used in addition to surgery to relieve a patient’s symptoms and
enhance quality of life. For patients with metastatic
disease, chemotherapy and radiation are used mainly
as palliative (pain alleviating) treatments.

Chemotherapy
Chemotherapeutic agents are powerful drugs that
are used to kill cancer cells. They are classified according to the mechanism by which they induce cancer cell
death. Multiple agents are often used to increase the
chances of tumor cell death. Gemcitabine is the standard drug used to treat pancreatic cancers and can
be used alone or in combination with other drugs,
such as 5-flourouracil (5-FU). Other drugs are being
tested in combination with gemcitabine in several
ongoing clinical trials, specifically irinotecan (CPT-11)
and oxaliplatin. Chemotherapy may be administered
orally or intravenously in a series of doses over several
weeks. During treatment, patients may experience
fatigue, nausea, vomiting, hair loss, and mouth sores,
depending on which drugs are used.

Surgery
Three types of surgery are used in the treatment of
pancreatic cancer, depending on what section of the
pancreas the tumor is located in. A Whipple procedure
removes the head of the pancreas, part of the small
intestine and some of the surrounding tissues. This
procedure is most common since the majority of
pancreatic cancers occur in the head of the organ. A
total pancreatectomy removes the entire pancreas and
the organs around it. Distal pancreatectomy removes
only the body and tail of the pancreas. Chemotherapy
and radiation may precede surgery (neoadjuvant therapy) or follow surgery (adjuvant therapy). Surgery is
also used to relieve symptoms of pancreatic cancer by
draining fluids or bypassing obstructions. Side effects
from surgery can include pain, weakness, fatigue, and
digestive problems. Some patients may develop
diabetes or malabsorption as a result of partial or
total removal of the pancreas.
Radiation therapy
Radiation therapy is sometimes used to shrink a
tumor before surgery or to remove remaining cancer
cells after surgery. Radiation may also be used to
relieve pain or digestive problems caused by the
tumor if it cannot be removed by surgery. External
radiation therapy refers to radiation applied externally
to the abdomen using a beam of high-energy x rays.
High-dose intraoperative radiation therapy is sometimes used during surgery on tumors that have spread
to nearby organs. Internal radiation therapy refers to
the use of small radioactive seeds implanted in the
tumor tissue. The seeds emit radiation over a period
of time to kill tumor cells. Radiation treatment may
cause side effects such as fatigue, tender or itchy skin,
nausea, vomiting, and digestive problems.
2772

Biological treatments
Numerous vaccine treatments are being developed in an effort to stimulate the body’s immune
system into attacking cancer cells. This is also referred
to as immunotherapy. Another type of biological
treatment involves using a targeted monoclonal antibody to inhibit the growth of cancer cells. The antibody is thought to bind to and neutralize a protein
that contributes to the growth of the cancer cells.
Investigational treatments such as these may be
considered by patients with metastatic disease who
would like to participate in a clinical trial. Biological
treatments typically cause flu-like symptoms (chills,
fever, loss of appetite) during the treatment period.

Alternative treatment
Acupuncture or hypnotherapy may be used in addition to standard therapies to help relieve the pain
associated with pancreatic cancer. Because of the
poor prognosis associated with pancreatic cancer,
some patients may try special diets with vitamin
supplements, certain exercise programs, or unconventional treatments not yet approved by the FDA.
Patients should always inform their doctors of any
alternative treatments they are using as they could
interfere with standard therapies. As of the year
2000, the National Cancer Institute (NCI) is funding
phase III clinical trials of a controversial treatment
for pancreatic cancer that involves the use of supplemental pancreatic enzymes (to digest cancerous
cells) and coffee enemas (to stimulate the liver to
detoxify the cancer). These theories remain unproven
and the study is widely criticized in the medical community. It remains to been seen whether this method
of treatment has any advantage over the standard
GALE ENCYCLOPEDIA OF MEDICINE

Acinar cell carcinoma—A malignant tumor arising
from the acinar cells of the pancreas.
Angiography—Diagnostic technique used to study
blood vessels in a tumor.
Biopsy—Removal and microscopic examination of
cells to determine whether they are cancerous.
Cancer vaccines—A treatment that uses the
patient’s immune system to attack cancer cells.
Chemotherapy—Drug treatment administered to
kill cancerous cells.
Ductal adenocarcinoma—A malignant tumor
arising from the duct cells within a gland.
Endoscopic retrograde cholangiopancreatography
(ERCP)—Diagnostic technique used to obtain a
biopsy. Also a surgical method of relieving biliary
obstruction caused by a tumor.
Endoscopic ultrasonography (EUS)—Diagnostic
imaging technique in which an ultrasound probe
is inserted down a patient’s throat to determine if a
tumor is present.
Exocrine—Refers to glands which secrete their
products through a duct.

patient survival after five years is only 10% to 15%.
These statistics demonstrate the aggressive nature of
most pancreatic cancers and their tendency to recur.
Pancreatic cancers tend to be resistant to radiation
and chemotherapy and these modes of treatment are
mainly used to relieve pain and tumor burden.

Prevention
Although the exact cause of pancreatic cancer is
not known, there are certain risk factors that may
increase a person’s chances of developing the disease.
Quitting smoking will certainly reduce the risk for
pancreatic cancer and many other cancers. The
American Cancer Society recommends a diet rich in
fruits, vegetables, and dietary fiber in order to reduce
the risk of pancreatic cancer. According to the NCI,
workers who are exposed to petroleum and other chemicals may be at greater risk for developing the disease
and should follow their employer’s safety precautions.
People with a family history of pancreatic cancer are at
greater risk than the general population, as a small
percentage of pancreatic cancers are considered
hereditary.
Resources
BOOKS

Laparoscopic surgery—Minimally invasive surgery
in which a camera and surgical instruments are
inserted through a small incision.

Teeley, Peter, and Philip Bashe. The Complete Cancer
Survival Guide. New York: Doubleday, 2000.

Pancreatectomy—Partial or total surgical removal
of the pancreas.
Radiation therapy—Use of radioisotopes to kill
tumor cells. Applied externally through a beam of
x rays, intraoperatively (during surgery), or deposited internally by implanting radioactive seeds in
tumor tissue.

Bornman, P. C., and I. J. Beckingham. ‘‘ABC of Diseases of
Liver, Pancreas, and Biliary System. Pancreatic
Tumours.’’ British Medical Journal 322, no. 7288
(24 March 2001): 721–3.
Haut, E., A. Abbas, and A. Schuricht. ‘‘Pancreatic Cancer:
The Role of the Primary Care Physican.’’ Consultant 39,
no. 12 (December 1999): 3329.
Parks, R. W., and O. J. Garden. ‘‘Ensuring Early Diagnosis
in Pancreatic Cancer.’’ Practitioner 244, no. 1609 (April
2000): 336–8, 340–1, 343.

Whipple procedure—Surgical removal of the head
of the pancreas, part of the small intestine, and
some surrounding tissue.

chemotherapeutic regimen in prolonging patient
survival or improving quality of life.

Prognosis
Unfortunately, cancer of the pancreas is often
fatal, and median survival from diagnosis is less than
six months, while the five-year survival rate is 4%.
This is mainly due to the lack of screening methods
available for early detection of the disease. Yet, even
when localized tumors can be removed by surgery,
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

ORGANIZATIONS

CancerNet. National Cancer Institute, 9000 Rockville Pike,
Bldg. 31, Rm.10A16, Bethesda, Maryland, 20892. (800)
422-6237. <http://wwwicic.nci.nih.gov>.
Hirshberg Foundation for Pancreatic Cancer Research. 375
Homewood Rd., Los Angeles, CA 90049. (310) 4726310. <http://www.pancreatic.org>.
National Pancreas Foundation. PO Box 935, Wexford, PA
15090-0935. <http://www.pancreasfoundation.org>.
Pancreatic Cancer Action Network. PO Box 1010, Torrance,
CA 90505. (877) 272-6226. <http://www.pancan.org>.
OTHER

Johns Hopkins Medical Institutions. July 20, 2001
<http://www.path.jhu.edu/pancreas>.
2773

Pancreatic cancer, exocrine

KEY TERMS

Pancreatitis

Memorial Sloan-Kettering Cancer Center. Patient
Information on Pancreatic Cancer. July 20, 2001.
<http://www.mskcc.org/patients_n_public/
about_cancer_and_treatment/
cancer_information_by_type/
pancreatic_cancer/index.html>.
University of Texas MD Anderson Cancer Center.
Pancreatic Tumor Study Group. July 20, 2001.
<http://www.mdanderson.org/DEPARTMENTS/
pancreatic/>.
‘‘What You Need To Know About Cancer of the Pancreas.’’
National Cancer Institute. December 12, 2000. [cited
July 20, 2001]. <http://cancernet.nci.nih.gov/
wyntk_pubs/pancreas.htm>.

Lata Cherath, PhD
Elizabeth Pulcini, MSc

begin the process of breaking down a variety of
food components, including, proteins, fats, and
starches.
Acute pancreatitis occurs when the pancreas
suddenly becomes inflamed but improves. Patients
recover fully from the disease, and in almost 90% of
cases the symptoms disappear within about a week
after treatment. The pancreas returns to its normal
architecture and functioning after healing from the
illness. After an attack of acute pancreatitis, tissue and
cells of the pancreas return to normal. With chronic
pancreatitis, damage to the pancreas occurs slowly over
time. Symptoms may be persistent or sporadic, but
the condition does not disappear and the pancreas is
permanently impaired. Pancreatic tissue is damaged,
and the tissue and cells function poorly.

Causes and symptoms

Pancreatitis
Definition
Pancreatitis is an inflammation of the pancreas, an
organ that is important in digestion. Pancreatitis can be
acute (beginning suddenly, usually with the patient
recovering fully) or chronic (progressing slowly with
continued, permanent injury to the pancreas).

There are a number of causes of acute pancreatitis. The most common, however, are gallbladder
disease and alcoholism. These two diseases are responsible for more than 80% of all hospitalizations for
acute pancreatitis. Other factors in the development
of pancreatitis include:


certain drugs



infections



structural problems of the pancreatic duct and bile
ducts (channels leading from the gallbladder to the
duodenum)



injury to the abdomen resulting in injury to the pancreas (including injuries occurring during surgery)



abnormally high levels of circulating fats in the
bloodstream



malfunction of the parathyroid gland, with high
blood levels of calcium



complications from kidney transplants



a hereditary tendency toward pancreatitis.

Description
The pancreas is located in the midline of the back
of the abdomen, closely associated with the liver,
stomach, and duodenum (the first part of the small
intestine). The pancreas is considered a gland. A
gland is an organ whose primary function is to
produce chemicals that pass either into the main
blood circulation (called an endocrine function), or
pass into another organ (called an exocrine function). The pancreas is unusual because it has both
endocrine and exocrine functions. Its endocrine
function produces three hormones. Two of these
hormones, insulin and glucagon, are central to the
processing of sugars in the diet (carbohydrate metabolism or breakdown). The third hormone produced
by the endocrine cells of the pancreas affects gastrointestinal functioning. This hormone is called
vasoactive intestinal polypeptide (VIP). The pancreas’s exocrine function produces a variety of digestive enzymes (trypsin, chymotrypsin, lipase, and
amylase, among others). These enzymes are passed
into the duodenum through a channel called the
pancreatic duct. In the duodenum, the enzymes
2774

Pancreatitis caused by drugs accounts for about
5% of all cases. Some drugs that are definitely related
to pancreatitis include:


Azathioprine, 6-mercaptopurine (Imuran)



Dideoxyinosine (Videx)



Estrogens (birth control pills)



Furosemide (Lasix)



Pentamidine (NebuPent)



Sulfonamides (Urobak, Azulfidine)



Tetracycline
GALE ENCYCLOPEDIA OF MEDICINE

Thiazide diuretics (Diuril, Enduron)



Valproic acid (Depakote).

Some drugs that are probably related to pancreatitis include:


Acetaminophen (Tylenol)



Angiotensin-converting enzyme (ACE) inhibitors
(Capoten, Vasotec)



Erythromycin



Methyldopa (Aldomet)



Metronidazole (Flagyl, Protostat)



Nitrofurantoin (Furadantin, Furan)



Nonsteroidal anti-inflammatory drugs (NSAIDs)
(Aleve, Naprosyn, Motrin)



Salicylates (aspirin).

All of these causes of pancreatitis seem to have
a similar mechanism in common. Under normal circumstances, many of the extremely potent enzymes
produced by the pancreas are not active until they
are passed into the duodenum, where contact with
certain other chemicals allow them to function. In
pancreatitis, something allows these enzymes to
become prematurely activated, so that they actually
begin their digestive functions within the pancreas.
The pancreas, in essence, begins digesting itself. A
cycle of inflammation begins, including swelling and
loss of function. Digestion of the blood vessels in the
pancreas results in bleeding. Other active pancreatic
chemicals cause blood vessels to become leaky, and
fluid begins leaking out of the normal circulation into
the abdominal cavity. The activated enzymes also gain
access to the bloodstream through leaky, eroded blood
vessels, and begin circulating throughout the body.
Pain is a major symptom in pancreatitis. The pain
is usually quite intense and steady, located in the upper
right hand corner of the abdomen, and often described
as ‘‘boring.’’ This pain is also often felt all the way
through to the patient’s back. The patient’s breathing
may become quite shallow because deeper breathing
tends to cause more pain. Relief of pain by sitting up
and bending forward is characteristic of pancreatic
pain. Nausea and vomiting, and abdominal swelling
are all common as well. A patient will often have a
slight fever, with an increased heart rate and low blood
pressure.
Classic signs of shock may appear in more severely
ill patients. Shock is a very serious syndrome that occurs
when the volume (quantity) of fluid in the blood is very
low. In shock, a patient’s arms and legs become extremely cold, the blood pressure drops dangerously low,
GALE ENCYCLOPEDIA OF MEDICINE

the heart rate is quite fast, and the patient may begin to
experience changes in mental status.
In very severe cases of pancreatitis (called necrotizing pancreatitis), the pancreatic tissue begins to die,
and bleeding increases. Due to the bleeding into the
abdomen, two distinctive signs may be noted in
patients with necrotizing pancreatitis. Turner’s sign
is a reddish-purple or greenish-brown color to the
flank area (the area between the ribs and the hip
bone). Cullen’s sign is a bluish color around the navel.
Some of the complications of pancreatitis are due
to shock. When shock occurs, all of the body’s major
organs are deprived of blood (and, therefore, oxygen),
resulting in damage. Kidney, respiratory, and heart
failure are serious risks of shock. The pancreatic
enzymes that have begun circulating throughout the
body (as well as various poisons created by the abnormal digestion of the pancreas by those enzymes) have
severe effects on the major body systems. Any number
of complications can occur, including damage to the
heart, lungs, kidneys, lining of the gastrointestinal tract,
liver, eyes, bones, and skin. As the pancreatic enzymes
work on blood vessels surrounding the pancreas, and
even blood vessels located at a distance, the risk of blood
clots increases. These blood clots complicate the situation by blocking blood flow in the vessels. When blood
flow is blocked, the supply of oxygen is decreased to
various organs and the organ can be damaged.
The pancreas may develop additional problems,
even after the pancreatitis decreases. When the entire
organ becomes swollen and suffers extensive cell death
(pancreatic necrosis), the pancreas becomes extremely
susceptible to serious infection. A local collection of
pus (called a pancreatic abscess) may develop several
weeks after the illness subsides, and may result in
increased fever and a return of pain. Another late
complication of pancreatitis, occurring several weeks
after the illness begins, is called a pancreatic pseudocyst. This occurs when dead pancreatic tissue, blood,
white blood cells, enzymes, and fluid leaked from the
circulatory system accumulate. In an attempt to
enclose and organize this abnormal accumulation,
a kind of wall forms from the dead tissue and the
growing scar tissue in the area. Pseudocysts cause
additional abdominal pain by putting pressure on
and displacing pancreatic tissue (resulting in more
pancreatic damage). Pseudocysts also press on other
nearby structures in the gastrointestinal tract, causing
more disruption of function. Pseudocysts are lifethreatening when they become infected (abscess) and
when they rupture. Simple rupture of a pseudocyst
causes death 14% of the time. Rupture complicated
by bleeding causes death 60% of the time.
2775

Pancreatitis



Pancreatitis

As the pancreatic tissue is increasingly destroyed
in chronic pancreatitis, many digestive functions
become disturbed. The quantity of hormones and
enzymes normally produced by the pancreas begins
to seriously decrease. Decreases in the production of
enzymes result in the inability to appropriately digest
food. Fat digestion, in particular, is impaired. A
patient’s stools become greasy as fats are passed out
of the body. The inability to digest and use proteins
results in smaller muscles (wasting) and weakness. The
inability to digest and use the nutrients in food leads
to malnutrition, and a generally weakened condition.
As the disease progresses, permanent injury to the
pancreas can lead to diabetes.

Diagnosis
Diagnosis of pancreatitis can be made very early
in the disease by noting high levels of pancreatic
enzymes circulating in the blood (amylase and lipase).
Later in the disease, and in chronic pancreatitis, these
enzyme levels will no longer be elevated. Because of
this fact, and because increased amylase and lipase
can also occur in other diseases, the discovery of
such elevations are helpful but not mandatory in the
diagnosis of pancreatitis. Other abnormalities in the
blood may also point to pancreatitis, including
increased white blood cells (occurring with inflammation and/or infection), changes due to dehydration
from fluid loss, and abnormalities in the blood
concentration of calcium, magnesium, sodium, potassium, bicarbonate, and sugars.
X rays or ultrasound examination of the abdomen
may reveal gallstones, perhaps responsible for blocking the pancreatic duct. The gastrointestinal tract will
show signs of inactivity (ileus) due to the presence of
pancreatitis. Chest x rays may reveal abnormalities
due to air trapping from shallow breathing, or due to
lung complications from the circulating pancreatic
enzyme irritants. Computed tomography scans (CT
scans) of the abdomen may reveal the inflammation
and fluid accumulation of pancreatitis, and may also
be useful when complications like an abscess or a
pseudocyst are suspected.
In the case of chronic pancreatitis, a number of
blood tests will reveal the loss of pancreatic function
that occurs over time. Blood sugar (glucose) levels will
rise, eventually reaching the levels present in diabetes.
The levels of various pancreatic enzymes will fall, as
the organ is increasingly destroyed and replaced
by non-functioning scar tissue. Calcification of the
pancreas can also be seen on x rays. Endoscopic retrograde cholangiopancreatography (ERCP) may be
2776

used to diagnose chronic pancreatitis in severe cases.
In this procedure, the doctor uses a medical instrument fitted with a fiber-optic camera to inspect the
pancreas. A magnified image of the area is shown on
a television screen viewed by the doctor. Many endoscopes also allow the doctor to retrieve a small sample
(biopsy) of pancreatic tissue to examine under a
microscope. A contrast product may also be used for
radiographic examination of the area.

Treatment
Treatment of pancreatitis involves quickly and
sufficiently replacing lost fluids by giving the patient
new fluids through a needle inserted in a vein (intravenous or IV fluids). These IV solutions need to
contain appropriate amounts of salts, sugars, and
sometimes even proteins, in order to correct the
patient’s disturbances in blood chemistry. Pain is treated with a variety of medications. In order to decrease
pancreatic function (and decrease the discharge of
more potentially harmful enzymes into the bloodstream), the patient is not allowed to eat. A thin,
flexible tube (nasogastric tube) may be inserted
through the patient’s nose and down into his or her
stomach. The nasogastric tube can empty the stomach
of fluid and air, which may accumulate due to the
inactivity of the gastrointestinal tract. Oxygen may
need to be administered by nasal prongs or by a mask.
The patient will need careful monitoring in order
to identify complications that may develop. Infections
(often occurring in cases of necrotizing pancreatitis,
abscesses, and pseudocysts) will require antibiotics
through the IV. Severe necrotizing pancreatitis may
require surgery to remove part of the dying pancreas.
A pancreatic abscess can be drained by a needle
inserted through the abdomen and into the collection
of pus (percutaneous needle aspiration). If this is
not sufficient, an abscess may also require surgical
removal. Pancreatic pseudocysts may shrink on their
own (in 25–40% of cases) or may continue to expand,
requiring needle aspiration or surgery. When diagnostic exams reveal the presence of gallstones, surgery
may be necessary for their removal. When a patient
is extremely ill from pancreatitis, however, such
surgery may need to be delayed until any infection is
treated, and the patient’s condition stabilizes.
Because chronic pancreatitis often includes
repeated flares of acute pancreatitis, the same kinds
of basic treatment are necessary. Patients cannot take
solids or fluids by mouth. They receive IV replacement
fluids, receive pain medication, and are monitored for
complications. Treatment of chronic pancreatitis
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Abscess—A pocket of infection; pus.
Acute—Of short and sharp course. Illnesses that
are acute appear quickly and can be serious or
life-threatening. The illness ends and the patient
usually recovers fully.
Chronic—Of long duration and slow progression.
Illnesses that are chronic develop slowly over time,
and do not end. Symptoms may be continual or
intermittent, but the patient usually has the condition for life.
Diabetes—A disease characterized by an inability
to process sugars in the diet, due to a decrease in or
total absence of insulin production. May require
injections of insulin before meals to aid in the
metabolism of sugars.

Prognosis
A number of systems have been developed to help
determine the prognosis of an individual with pancreatitis. A very basic evaluation of a patient will allow
some prediction to be made based on the presence of
dying pancreatic tissue (necrosis) and bleeding. When
necrosis and bleeding are present, as many as 50% of
patients may die.

Duodenum—The first section of the small intestine
that receives partly digested material from the
stomach.
Endocrine—A system of organs that produces chemicals that go into the bloodstream to reach other
organs whose functioning they affect.

More elaborate systems have been created to help
determine the prognosis of patients with pancreatitis.
The most commonly used system identifies 11 different
signs (Ranson’s signs) that can be used to determine
the severity of the disease. The first five categories are
evaluated when the patient is admitted to the hospital:


age over 55 years



blood sugar level over 200 mg/Dl



serum lactic dehydrogenase over 350 IU/L (increased
with increased breakdown of blood, as would occur
with internal bleeding, and with heart or liver damage)



AST over 250 mu (a measure of liver function, as well
as a gauge of damage to the heart, muscle, brain, and
kidney)



white blood count over 16,000 u L

Pancreatitis

caused by alcohol consumption requires that the
patient stop drinking alcohol entirely. As chronic
pancreatitis continues and insulin levels drop, a
patient may require insulin injections in order to be
able to process sugars in his or her diet. Pancreatic
enzymes can be replaced with oral medicines, and
patients sometimes have to take as many as eight
pills with each meal. As the pancreas is progressively
destroyed, some patients stop feeling the abdominal
pain that was initially so severe. Others continue to
have constant abdominal pain, and may even require a
surgical procedure for relief. Drugs can be used to
reduce the pain, but when narcotics are used for pain
relief there is danger of the patient becoming addicted.

Enzyme—A chemical that speeds up or makes a
particular chemical reaction more efficient. In the
digestive system, enzymes are involved in breaking
down large food molecules into smaller molecules
that can be processed and utilized by the body.
Exocrine—A system of organs that produces chemicals that go through a duct (or tube) to reach
other organs whose functioning they affect.
Gland—Collections of tissue that produce chemicals needed for chemical reactions elsewhere in
the body.
Hormone—A chemical produced in one part of the
body that travels to another part of the body in
order to exert an effect.

The next six of Ranson’s signs are reviewed 48
hours after admission to the hospital. These are:


greater than 10% decrease in hematocrit (a measure
of red blood cell volume)



increase in BUN greater than 5 mg/dL (blood urea
nitrogen, an indicator of kidney function)



blood calcium less than 8 mg/dL



PaO2 less than 60 mm Hg (a measure of oxygen in
the blood)



base deficit greater than 4 mEg/L (a measure of
change in the normal acidity of the blood)

GALE ENCYCLOPEDIA OF MEDICINE



fluid sequestration greater than 6 L (an estimation of
the quantity of fluid that has leaked out of the blood
circulation and into other body spaces)

Once a doctor determines how many of Ranson’s
signs are present and gives the patient a score, the
doctor can better predict the risk of death. The more
signs present, the greater the chance of fatal complications. A patient with less than three positive Ranson’s
signs has a 95% survival rate. A patient with three to
four positive Ranson’s signs has a 80-85% survival rate.
2777

Panic disorder

The results of a CT scan can also be used to
predict the severity of pancreatitis. Slight swelling
of the pancreas indicates mild illness. Significant
swelling, especially with evidence of destruction of
the pancreas and/or fluid build-up in the abdominal
cavity, indicates more severe illness. With severe
illness, there is a worse prognosis.

Prevention
Alcoholism is essentially the only preventable
cause of pancreatitis. Patients with chronic pancreatitis
must stop drinking alcohol entirely. The drugs that
cause or may cause pancreatitis should also be avoided.
Resources

only seconds or minutes, the experience can be profoundly disturbing. A person who has had one panic
attack typically worries that another one may occur at
any time.
As the fear of future panic attacks deepens, the
person begins to avoid situations in which panic
occurred in the past. In severe cases of panic disorder,
the victim refuses to leave the house for fear of having
a panic attack. This fear of being in exposed places is
often called agoraphobia.
People with untreated panic disorder may have
problems getting to work or staying on the job. As
the person’s world narrows, untreated panic disorder
can lead to depression, substance abuse, and in rare
instances, suicide.

ORGANIZATIONS

National Digestive Diseases Information Clearinghouse. 2
Information Way, Bethesda, MD 20892-3570. (800)
891-5389. <http://www.niddk.nih.gov/health/
digest/nddic.htm>.

Rosalyn Carson-DeWitt, MD

Panic attack see Panic disorder

Panic disorder
Definition
A panic attack is a sudden, intense experience of
fear coupled with an overwhelming feeling of danger,
accompanied by physical symptoms of anxiety, such
as a pounding heart, sweating, and rapid breathing. A
person with panic disorder may have repeated panic
attacks (at least several a month) and feel severe anxiety about having another attack.

Description
Each year, panic disorder affects one out of 63
Americans. While many people experience moments
of anxiety, panic attacks are sudden and unprovoked,
having little to do with real danger.
Panic disorder is a chronic, debilitating condition
that can have a devastating impact on a person’s
family, work, and social life. Typically, the first attack
strikes without warning. A person might be walking
down the street, driving a car, or riding an escalator
when suddenly panic strikes. Pounding heart, sweating palms, and an overwhelming feeling of impending
doom are common features. While the attack may last
2778

Causes and symptoms
Scientists are not sure what causes panic disorder,
but they suspect the tendency to develop the condition
can be inherited. Some experts think that people with
panic disorder may have a hypersensitive nervous
system that unnecessarily responds to nonexistent
threats. Research suggests that people with panic
disorder may not be able to make proper use of their
body’s normal stress-reducing chemicals.
People with panic disorder usually have their first
panic attack in their 20s. Four or more of the following
symptoms during panic attacks would indicate panic
disorder if no medical, drug-related, neurologic, or
other psychiatric disorder is found:


pounding, skipping or palpitating heartbeat



shortness of breath or the sensation of smothering



dizziness or lightheadedness



nausea or stomach problems



chest pains or pressure



choking sensation or a ‘‘lump in the throat’’



chills or hot flashes



sweating



fear of dying



feelings of unreality or being detached



tingling or numbness



shaking and trembling



fear of losing control or going crazy

A panic attack is often accompanied by the urge
to escape, together with a feeling of certainty that
death is imminent. Others are convinced they are
about to have a heart attack, suffocate, lose control,
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Because its physical symptoms are easily confused
with other conditions, panic disorder often goes
undiagnosed. A thorough physical examination is
needed to rule out a medical condition. Because the
physical symptoms are so pronounced and frightening,
panic attacks can be mistaken for a heart problem.
Some people experiencing a panic attack go to an
emergency room and endure batteries of tests until a
diagnosis is made.
Once a medical condition is ruled out, a mental
health professional is the best person to diagnose
panic attack and panic disorder, taking into account
not just the actual episodes, but how the patient feels
about the attacks, and how they affect everyday life.
Most health insurance policies include some
limited amount of mental health coverage, although
few completely cover outpatient mental health care.

Treatment
Most patients with panic disorder respond best to
a combination of cognitive-behavioral therapy and
medication. Cognitive-behavioral therapy usually
runs from 12–15 sessions. It teaches patients:


how to identify and alter thought patterns so as not
to misconstrue bodily sensations, events, or situations
as catastrophic



how to prepare for the situations and physical symptoms that trigger a panic attack



how to identify and change unrealistic self-talk (such
as ‘‘I’m going to die!’’) that can worsen a panic
attack



how to calm down and learn breathing exercises to
counteract the physical symptoms of panic



how to gradually confront the frightening situation
step by step until it becomes less terrifying



how to ‘‘desensitize’’ themselves to their own physical sensations, such as rapid heart rate

At the same time, many people find that medications can help reduce or prevent panic attacks by
changing the way certain chemicals interact in the
brain. People with panic disorder usually notice
whether or not the drug is effective within two months,
GALE ENCYCLOPEDIA OF MEDICINE

but most people take medication for at least six
months to a year.
Several kinds of drugs can reduce or prevent panic
attacks, including:


selective serotonin reuptake inhibitor (SSRI) antidepressants like paroxetine (Paxil) or fluoxetine
(Prozac), are approved specifically for the treatment
of panic



tricyclic antidepressants such as clomipramine
(Anafranil)



benzodiazepines such as alprazolam (Xanax) and
clonazepam (Klonopin)

Finally, patients can make certain lifestyle
changes to help keep panic at bay, such as eliminating
caffeine and alcohol, cocaine, amphetamines, and
marijuana.

Alternative treatment
One approach used in several medical centers
focuses on teaching patients how to accept their fear
instead of dreading it. In this method, the therapist
repeatedly stimulates a person’s body sensations
(such as a pounding heartbeat) that can trigger fear.
Eventually, the patient gets used to these sensations
and learns not to be afraid of them. Patients who
respond report almost complete absence of panic
attacks.
A variety of other atlernative therapies may
be helpful in treating panic attacks. Neurolinguistic
programming and hypnotherapy can be beneificial,
since these techniques can help bring an awareness
of the root cause of the attacks to the conscious mind.
Herbal remedies, including lemon balm (Melissa officinalis), oat straw (Avena sativa), passionflower
(Passiflora incarnata), and skullcap (Scutellaria lateriflora), may help significantly by strengthening the
nervous system. Homeopathic medicine, nutritional
supplementation (especially with B vitamins, magnesium, and antioxidant vitamins), creative visualization, guided imagery, and relaxation techniques
may help some people experiencing panic attacks.
Hydrotherapies, especially hot epsom salt baths or
baths with essential oil of lavender (Lavandula officinalis), can help patients relax.

Prognosis
While there may be occasional periods of
improvement, the episodes of panic rarely disappear
on their own. Fortunately, panic disorder responds
very well to treatment; panic attacks decrease in up
2779

Panic disorder

or ‘‘go crazy.’’ Once people experience a panic attack,
they tend to worry so much about having another
attack that they avoid the place or situation associated
with the original episode.

Pap test

KEY TERMS
Agoraphobia—Fear of open spaces.
Benzodiazepines—A class of drugs that have a
hypnotic and sedative action, used mainly as tranquilizers to control symptoms of anxiety or panic.
Cognitive-behavioral therapy—A type of psychotherapy used to treat anxiety disorders (including
panic disorder) that emphasizes behavioral change
together with alteration of negative thought patterns.
Selective serotonin reuptake inhibitors (SSRIs)—A
class of antidepressants used to treat panic that
affects mood by boosting the levels of the brain
chemical serotonin.
Tricyclic antidepressants—A class of antidepressants named for their three-ring structure that
increase the levels of serotonin and other brain
chemicals. They are used to treat depression and
anxiety disorders, but have more side effects than
the newer class of antidepressants called SSRIs.

National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.
National Anxiety Foundation. 3135 Custer Dr., Lexington,
KY 40517. (606) 272-7166. <http://www.lexington-online.com/naf.html>.
National Institute of Mental Health, Panic Campaign. Rm
15C-05, 5600 Fishers Lane, Rockville, MD 20857. (800)
647-2642. <http://www.nimh.nih.gov>.
National Mental Health Association. 1021 Prince St.,
Alexandria, VA 22314. (703) 684-7722.
<http://www.nmha.org>.
OTHER

The Anxiety and Panic Internet Resource.
<http://www.algy.com/anxiety>.
Anxiety Network Page. <http://
www.anxietynetwork.com>.
National Institute of Mental Health Page.
<http://www.nimh.nih.gov>.
‘‘Panic Disorder.’’ Internet Mental Health Page.
<http://www.mentalhealth.com>.

Carol A. Turkington

to 90% of people after 6-8 weeks of a combination of
cognitive-behavioral therapy and medication.
Unfortunately, many people with panic disorder
never get the help they need. If untreated, panic disorder can last for years and may become so severe that
a normal life is impossible. Many people who struggle
with untreated panic disorder and try to hide their
symptoms end up losing their friends, family, and jobs.

Prevention
There is no way to prevent the initial onset of
panic attacks. Antidepressant drugs or benzodiazepines can prevent future panic attacks, especially
when combined with cognitive-behavioral therapy.
There is some suggestion that avoiding stimulants
(including caffeine, alcohol, or over-the-counter cold
medicines) may help prevent attacks as well.
Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington, DC 20005. (888) 357-7924.
<http://www.psych.org>.
Anxiety Disorders Association of America. 11900 Park
Lawn Drive, Ste. 100, Rockville, MD 20852. (800)
545-7367. <http://www.adaa.org>.
Freedom From Fear. 308 Seaview Ave., Staten Island, NY
10305. (718) 351-1717.
2780

Pap test
Definition
The Pap test is a procedure in which a physician
scrapes cells from the cervix or vagina to check for
cervical cancer, vaginal cancer, or abnormal changes
that could lead to cancer. It often is called a ‘‘Pap
smear.’’

Purpose
The Pap test is used to detect abnormal growth of
cervical cells at an early stage so that treatment can be
started when the condition is easiest to treat. This
microscopic analysis of cells can detect cervical cancer,
precancerous changes, inflammation (vaginitis), infections, and some sexually transmitted diseases (STDs).
The Pap test can occasionally detect endometrial
(uterine) cancer or ovarian cancer, although it was
not designed for this purpose.
Women should begin to have Pap tests at the age
of 21 or within three years of becoming sexually active,
whichever comes first. Young people are more likely
to have multiple sex partners, which increases their
risk of certain diseases that can cause cancer, such as
human papillomavirus (HPV).
GALE ENCYCLOPEDIA OF MEDICINE

Women with certain risk factors may have yearly
tests. Those at highest risk for cervical cancer are
women who started having sex before age 18, those
with many sex partners (especially if they did not use
condoms, which protect against STDs), those who
have had STDs such as genital herpes or genital
warts, and those who smoke. Women older than 40
may have the test yearly, if experiencing bleeding after
menopause. Women who have had a positive test result
in the past may need screening every six months.
Women who have had cervical cancer or precancer
should have regular Pap smears.
Other women also benefit from the Pap test.
Women over age 65 account for 25% of all cases of
cervical cancer and 41% of deaths from this disease.
Women over age 65 who have never had a Pap smear
benefit the most from the test. Some women have
the cervix left in place after hysterectomy and will
continue to receive regular Pap tests. Finally, a pregnant woman should have a Pap test as part of her first
prenatal examination.
The Pap smear is a screening test. It identifies
women who are at increased risk of cervical dysplasia
(abnormal cells) or cervical cancer. Only an examination of the cervix with a special lighted instrument
(colposcopy) and samples of cervical tissue (biopsies)
can actually diagnose these problems.

Precautions
The Pap test is usually not done during the menstrual period because of the presence of blood cells.
The best time is in the middle of the menstrual cycle.

Description
The Pap test is an extremely cost-effective and
beneficial exam. Cervical cancer used to be a leading
GALE ENCYCLOPEDIA OF MEDICINE

cause of cancer deaths in American women, but widespread use of this diagnostic procedure reduced the
death rate from this disease by 74% between 1955 and
1992. A 2003 study reported that the test reduces rates
of invasive cervical cancer by as much as 94%. In 2003,
the FDA approved a new screening test that combines
DNA testing for the HPV type that causes the most
cases of cervical cancer with the standard Pap test,
increasing its screening value.
The Pap test, sometimes called a cervical smear, is
the microscopic examination of cells scraped from
both the outer cervix and the cervical canal. (The
cervix is the opening between the vagina and the
uterus, or womb.) It is called the ‘‘Pap’’ test after its
developer, Dr. George N. Papanicolaou. This simple
procedure is performed during a gynecologic examination and is usually covered by insurance. For those
with coverage, Medicare will pay for one screening
Pap smear every three years.
During the pelvic examination, an instrument
called a speculum is inserted into the vagina to open
it. The doctor then uses a tiny brush, or a cottontipped swab and a small spatula to wipe loose cells
off the cervix and to scrape them from the inside of the
cervix. The cells are transferred or ‘‘smeared’’ onto
glass slides, the slides are treated to stabilize the cells,
and the slides are sent to a laboratory for microscopic
examination. The entire procedure is usually painless
and takes five to 10 minutes at most.
The newer method called liquid-based cytology,
or the liquid-based Pap test, involves spreading the
cells more evenly on a slide after removing them
from the sample. The liquid-based method prevents
cells from drying out and becoming distorted. Studies
show that liquid-based testing slightly improves cancer detection and greatly improves detection of precancers, but it costs more than the traditional Pap test.
Trade names in 2003 for liquid-based Pap smears were
ThinPrep and AutoCyte.

Preparation
The Pap test may show abnormal results when a
woman is healthy or normal results in women with
cervical abnormalities as much as 25% of the time. It
may even miss up to 5% of cervical cancers. Some
simple preparations may help to ensure that the results
are reliable. Among the measures that may help
increase test reliability are:


avoiding sexual intercourse for two days before the test



not using douches for two or three days before the
test
2781

Pap test

The American Cancer Society (ACS) updated its
guidelines concerning Pap test frequency in late 2002.
In brief, women should continue screening every year
with regular Pap tests until age 30, every two years if
using the liquid-based Pap test. Once a woman age 30
and older has had three normal results in a row, she
may get screened every two to three years. A doctor
may suggest more frequent screening if a woman has
certain risk factors for cervical cancer. Women who
have had total hysterectomies including the removal of
the cervix do not need Pap tests unless the hysterectomy resulted from cervical cancer. Those over age 70
who have had three normal results generally do not
need to continue having Pap tests under the new
guidelines.

Pap test

Vagina

Spatula

Uterus

Speculum
Cervix

The Pap test is a procedure used to detect abnormal growth of cervical cells which may be a precursor to cancer of the cervix. It is
administered by a physician who inserts a speculum into the vagina to open and separate the vaginal walls. A spatula is then
inserted to scrape cells from the cervix. These cells are transferred onto glass slides for laboratory analysis. The Pap test may
also identify vaginitis, some sexually transmitted diseases, and cancers of the uterus and ovaries. (Illustration by Electronic
Illustrators Group.)



avoiding tampons, vaginal creams, or birth control
foams or jellies for two to three days before the test



scheduling the Pap smear when not menstruating.

However, most women are not routinely advised
to make any special preparations for a Pap test.
If possible, women may want to ensure that their
test is performed by an experienced gynecologist, physician, or provider and sent to a reputable laboratory.
The physician should be confident in the accuracy of
the chosen lab.
Before the exam, the physician will take a complete sexual history to determine a woman’s risk status
for cervical cancer. Questions may include date and
results of the last Pap test, any history of abnormal
Pap tests, date of last menstrual period and any irregularity, use of hormones and birth control, family
history of gynecologic disorders, and any vaginal
symptoms. These topics are relevant to the interpretation of the Pap test, especially if any abnormalities are
detected. Immediately before the Pap test, the woman
should empty her bladder to avoid discomfort during
the procedure.

Aftercare
Harmless cervical bleeding is possible immediately after the test; a woman may need to use a sanitary
napkin. She should also be sure to comply with her
doctor’s orders for follow-up visits.
2782

Risks
No appreciable health risks are associated with
the Pap test. However, abnormal results (whether
valid or due to technical error) can cause significant
anxiety. Women may wish to have their sample doublechecked, either by the same laboratory or by the new
technique of computer-assisted rescreening. The Food
and Drug Administration (FDA) has approved the
use of AutoPap and PAPNET to doublecheck samples
that have been examined by technologists. AutoPap
may also be used to perform initial screening of slides,
which are then checked by a technologist. Any abnormal Pap test should be followed by colposcopy, not by
double checking the Pap test.

Normal results
Normal (negative) results from the laboratory
exam mean that no atypical, dysplastic, or cancer
cells were detected, and the cervix is normal.

Abnormal results
Terminology
Abnormal cells found on the Pap test may be
described using two different grading systems.
Although this can be confusing, the systems are quite
similar. The Bethesda system is based on the term
‘‘squamous intraepithelial lesion’’ (SIL). Precancerous
cells are classified as atypical squamous cells of
GALE ENCYCLOPEDIA OF MEDICINE

The next most common finding (in about 25 of
every 1,000 tests) is low-grade SIL, which includes
mild dysplasia or CIN I and changes caused by HPV.
Unlike cancer cells, these cells do not invade normal
tissues. Women are most susceptible to cervical
dysplasia between the ages of 25 and 35. Typically,
dysplasia causes no symptoms, although women may
experience abnormal vaginal bleeding. Because
dysplasia is precancerous, it should be treated if it is
moderate or severe.

These malignant cells were taken from a woman’s cervix
during a Pap test. (Photograph by Parviz M. Pour, Photo
Researchers, Inc. Reproduced by permission.)

undetermined significance, low-grade SIL, or highgrade SIL. Low-grade SIL includes mild dysplasia
(abnormal cell growth) and abnormalities caused by
HPV; high-grade SIL includes moderate or severe
dysplasia and carcinoma in situ (cancer that has not
spread beyond the cervix).
Another term that may be used is ‘‘cervical
intraepithelial neoplasia’’ (CIN). In this classification system, mild dysplasia is called CIN I, moderate
is CIN II, and severe dysplasia or carcinoma in situ is
CIN III.
Regardless of terminology, it is important to
remember that an abnormal (positive) result does not
necessarily indicate cancer. Results may be falsely
abnormal after infection or irritation of the cervix.
Up to 40% of mild dysplasia reverts to normal tissue
without treatment, and only 1% of mild abnormalities
ever develop into cancer.
Changes of unknown cause
ASCUS or LSIL cells are found in 5%–10% of all
Pap tests. The most common abnormality is atypical
squamous cells of undetermined significance, which
are found in 4% of all Pap tests. Sometimes these
results are described further as either reactive or precancerous. Reactive changes suggest that the cervical
cells are responding to inflammation, such as from
a yeast infection. These women may be treated for
infection and then undergo repeat Pap testing in
three to six months. If those results are negative, no
further treatment is necessary. This category may also
include atypical ‘‘glandular’’ cells, which could imply a
more severe type of cancer and requires repeat testing
and further evaluation.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment of dysplasia depends on the degree of
abnormality. In women with no other risk factors for
cervical cancer, mild precancerous changes may be
simply observed over time with repeat testing, perhaps
every four to six months. This strategy works only if
women are diligent about keeping later appointments.
Premalignant cells may remain that way without causing cancer for five to ten years, and may never become
malignant.
In women with positive results or risk factors, the
gynecologist must perform colposcopy and biopsy. A
colposcope is an instrument that looks like binoculars,
with a light and a magnifier, used to view the cervix.
Biopsy, or removal of a small piece of abnormal cervical or vaginal tissue for analysis, is usually done at the
same time.
High-grade SIL (found in three of every 50 Pap
tests) includes moderate to severe dysplasia or carcinoma in situ (CIN II or III). After confirmation by
colposcopy and biopsy, it must be removed or
destroyed to prevent further growth. Several outpatient techniques are available: conization (removal of a
cone-shaped piece of tissue), laser surgery, cryotherapy
(freezing), or the ‘‘loop electrosurgical excision procedure.’’ Cure rates are nearly 100% after prompt and
appropriate treatment of carcinoma in situ. Of course,
frequent checkups are then necessary.
Cancer
HPV, the most common STD in the United
States, may be responsible for many cervical cancers.
Cancer may be manifested by unusual vaginal bleeding or discharge, bowel and bladder problems,
and pain. Women are at greatest risk of developing
cervical cancer between the ages of 30 and 40 and
between the ages of 50 and 60. Most new cancers are
diagnosed in women between 50 and 55. Although
the likelihood of developing this disease begins to
level off for Caucasian women at the age of 45, it
increases steadily for African Americans for another
2783

Pap test

Dysplasia

Papilledema

Resources

KEY TERMS
Carcinoma in situ—Malignant cells that are present
only in the outer layer of the cervix.
Cervical intraepithelial neoplasia (CIN)—A term
used to categorize degrees of dysplasia arising in
the epithelium, or outer layer, of the cervix.
Dysplasia—Abnormal changes in cells.
Human papillomavirus (HPV)—The most common
STD in the United States. Various types of HPV are
known to cause cancer.
Neoplasia—Abnormal growth of cells, which may
lead to a neoplasm, or tumor.
Squamous intraepithelial lesion (SIL)—A term used
to categorize the severity of abnormal changes
arising in the squamous, or outermost, layer of the
cervix.

PERIODICALS

‘‘American Cancer Society Issues New Early Detection
Guidelines.’’ Women’s Health Weekly December 19,
2002: 12.
Law, Malcolm. ‘‘How Frequently Should Cervical
Screening Be Conducted.’’ Important Journal of
Medical Screening (Winter 2003): 159–161.
OTHER

‘‘Pap smear: Simple, life-saving test.’’ April 29, 1999.
April 26, 2001. [cited June 28, 2001]. <http://
www.mayohealth.org/home?id=HQ01177>.
‘‘Pap Smears: The simple test that can save your life.’’
January 29, 2001. April 26, 2001. [cited June 28, 2001].
<http://www.mayohealth.org/home?id=HQ01178>.

Laura J. Ninger
Teresa G. Odle

Papanicolaou test see PAP test
40 years. Biopsy is indicated when any abnormal
growth is found on the cervix, even if the Pap test is
negative.
Doctors have traditionally used radiation therapy
and surgery to treat cervical cancer that has spread
within the cervix or throughout the pelvis. In severe
cases, postoperative radiation is administered to kill
any remaining cancer cells, and chemotherapy may be
used if cancer has spread to other organs. Recent
studies have shown that giving chemotherapy and
radiation at the same time improves a patient’s
chance of survival. The National Cancer Institute
has urged physicians to strongly consider using both
chemotherapy and radiation to treat patients with
invasive cervical cancer. The survival rate at five
years after treatment of early invasive cancer is
91%; rates are below 70% for more severe invasive
cancer. That is why prevention, risk reduction, and
frequent Pap tests are the best defense for a woman’s
gynecologic health.
The Pap test is a procedure used to detect abnormal growth of cervical cells which may be a precursor
to cancer of the cervix. It is administered by a physician who inserts a speculum into the vagina to open
and separate the vaginal walls. A spatula is then
inserted to scrape cells from the cervix. These cells
are transferred onto glass slides for laboratory analysis. The Pap test may also identify vaginitis, some
sexually transmitted diseases, and cancers of the
uterus and ovaries.
2784

Papilledema
Definition
Papilledema is a swelling of the optic nerve, at the
point where this nerve joins the eye, that is caused by
an increase in fluid pressure within the skull (intracranial pressure). Swelling of the optic nerve due to other
causes such as infection or inflammatory disease is not
called papilledema.

Description
The optic nerve is the nerve that transmits signals
from the eye to the brain. Papilledema is a swelling of
this nerve where it meets the eye (the optic disc) caused
by an increase in intracranial pressure. Almost all
cases of papilledema are bilateral (affect both eyes).
Papilledema can be observed in people of any age, but
is relatively uncommon in infants because the bones of
the skull are not fully fused together at this age.

Causes and symptoms
Papilledema is caused by an increase in the pressure
of the fluid (cerebrospinal fluid) that is present between
the brain and the skull, inside the head. This increase in
intracranial pressure may be caused by any of a variety
of conditions within the skull, brain, or spinal cord. The
most common causes of papilledema are:
GALE ENCYCLOPEDIA OF MEDICINE

tumor of the brain, spinal cord, skull, spinal column,
or optic nerve



abscess (the accumulation of pus within a confined
space)



craniosynostosis (an abnormal closure of the bones
of the skull)



hemorrhage (bleeding)



hydrocephalus (an accumulation of cerebrospinal
fluid within the skull)



intracranial infection (any infection within the skull
such as meningitis and encephalitis)



head injury
The symptoms of papilledema include:



headaches, which are usually worse upon awakening
and exacerbated by coughing, holding the breath, or
other maneuvers that tend to increase intracranial
pressure.



nausea and vomiting.



changes in vision, such as temporary and transient
blurring, graying, flickering, or double vision

Diagnosis
A diagnosis of papilledema is achieved by visual
examination of the eye with an ophthalmoscope. This
instrument shines light through the pupil of the eye
and illuminates the retina while the clinician looks
through it. Eye drops to dilate the pupils are used to
insure a thorough examination.

Treatment
Treatment of papilledema is generally aimed at
the treatment of the underlying disorder that is causing papilledema.

KEY TERMS
Craniosynostosis—A premature closure of one or
more of the joints (fissures) between the bones of
the skull, which causes an abnormally shaped skull.
Hydrocephalus—The accumulation of cerebrospinal fluid within the skull.
Ophthalmoscope—A medical instrument which
shines a light through the pupil of the patient’s eye
and illuminates the retina (back) of the eye, allowing a visual examination of the interior of the eye.

Prognosis
With prompt medical care to treat the underlying
cause of papilledema, a person affected with papilledema will not have permanent damage to his or her
eye-sight. However, prolonged papilledema can result
in permanent damage to the optic nerve which could
lead to blindness.

Prevention
Preventing papilledema is only possible if the
underlying condition causing the papilledema can be
found. Treatment of this underlying condition may
prevent recurrences of papilledema.
Resources
BOOKS

Rhee, Douglas J., and Mark F. Pyfer. The Wills Eye Manual.
3rd ed. Philadelphia, PA: Lippincott Williams and
Wilkins, 1999.
PERIODICALS

Agarwal, A. K., et al. ‘‘Papilledema.’’ Journal of the
Indian Academy of Clinical Medicine 1 (OctoberDecember 2000): 270-277.

Diuretic drugs combined with a weight reduction
program may be useful in cases of papilledema that
are caused by an abnormally high production of
cerebrospinal fluid.

ORGANIZATIONS

Corticosteroids have been shown to be effective in
relieving the symptoms in some patients with papilledema caused by inflammatory disorders.

OTHER

National Eye Institute. 2020 Vision Place, Bethesda, MD
20892-3655. (301) 496-5248. <http://
www.nei.nih.gov/>.
Giovannini, Joseph, and Georgia Chrousos. ‘‘Papilledema.’’
eMedicine. May 12, 2001. <http://www.emedicine.
com/OPH/topic187.htm>.

Alternative treatment
Alternative treatments for conditions that cause
the occurrence of papilledema include acupuncture,
aromatherapy, hydrotherapy, massage, and herbal
remedies.
GALE ENCYCLOPEDIA OF MEDICINE

Paul A. Johnson, Ed.M.

Papillomavirus infection see Genital warts
Papule see Skin lesions
2785

Papilledema



Paracentesis

Cancer

Paracentesis
Definition
Paracentesis is a procedure during which fluid
from the abdomen is removed through a needle.

Any cancer that begins in or spreads to the abdomen can leak fluid. One particular tumor of the ovary
that leaks fluid, the resulting presentation of the disease, is Meigs’ syndrome.
Kidney disease

Purpose
There are two reasons to take fluid out of the
abdomen. One is to analyze it. The other is to relieve
pressure.
Liquid that accumulates in the abdomen is called
ascites. Ascites seeps out of organs for several reasons
related either to disease in the organ or fluid pressures
that are changing.
Liver disease
All the blood flowing through the intestines passes
through the liver on its way back to the heart. When
progressive disease such as alcohol damage or hepatitis destroys enough liver tissue, the scarring that
results shrinks the liver and constricts the blood flow.
Such scarring of the liver is called cirrhosis. Pressure
builds up in the intestinal circulation, slowing flow
and pushing fluid into the tissues. Slowly the fluid
accumulates in areas with the lowest pressure and
greatest capacity. The free space around abdominal
organs receives most of it. This space is called the
peritoneal space because it is enclosed by a thin membrane called the peritoneum. The peritoneum wraps
around nearly every organ in the abdomen, providing
many folds and spaces for the fluid to gather.
Infections
Peritonitis is an infection of the peritoneum.
Infection changes the dynamics of body fluids, causing
them to seep into tissues and spaces. Peritonitis can
develop in several ways. Many abdominal organs
contain germs that do not belong elsewhere in the
body. If they spill their contents into the peritoneum,
infection is the result. The gall bladder, the stomach,
any part of the intestine, and most especially the
appendix–all cause peritonitis when they leak or rupture. Tuberculosis can infect many organs in the body;
it is not confined to the lungs. Tuberculous peritonitis
causes ascites.
Other inflammations
Peritoneal fluid is not just produced by infections.
The pancreas can cause a massive sterile peritonitis
when it leaks its digestive enzymes into the abdomen.
2786

Since the kidneys are intimately involved with the
body’s fluid balance, diseases of the kidney often cause
excessive fluid to accumulate. Nephrosis and nephrotic syndrome are the general terms for diseases that
cause the kidneys to retain water and provoke its
movement into body tissues and spaces.
Heart failure
The ultimate source of fluid pressure in the body is
the heart, which generates blood pressure. All other
pressures in the body are related to blood pressure. As
the heart starts to fail, blood backs up, waiting to be
pumped. This increases back pressure upstream, particularly below the heart where gravity is also pulling
blood away from the heart. The extra fluid from heart
failure is first noticed in the feet and ankles, where
gravitational effects are most potent. In the abdomen,
the liver swells first, then it and other abdominal
organs start to leak.
Pleural fluid
The other major body cavity is the chest. The
tissue in the chest corresponding to the peritoneum is
called the pleura, and the space contained within the
pleura, between the ribs and the lungs, is called the
pleural space. Fluid is often found in both cavities, and
fluid from one cavity can find its way into the other.
Fluid that accumulates in the abdomen creates
abnormal pressures on organs in the abdomen.
Digestion is hindered; blood flow is slowed. Pressure
upward on the chest compromises breathing. The kidneys function poorly in the presence of such external
pressures and may even fail with tense, massive ascites.

Description
During paracentesis, special needles puncture the
abdominal wall, being careful not to hit internal
organs. If fluid is needed only for analysis, just a bit
is removed. If pressure relief is an additional goal,
many quarts may be removed. Rapid removal of
large amounts of fluid can cause blood pressure to
drop suddenly. For this reason, the physician will
often leave a tube in place so that fluid can be removed
slowly, giving the circulation time to adapt.
GALE ENCYCLOPEDIA OF MEDICINE

Ectopic pregnancy—A pregnancy occurring outside the womb that often ruptures and requires
surgical removal.

Paralysis

KEY TERMS

Paralysis
Definition
Paralysis is defined as complete loss of strength in
an affected limb or muscle group.

Description
A related procedure called culpocentesis removes
ascitic fluid from the very bottom of the abdominal
cavity through the back of the vagina. This is used
mostly to diagnose female genital disorders like
ectopic pregnancy that bleed or exude fluid into the
peritoneal space.
Fluid is sent to the laboratory for testing, where
cancer and blood cells can be detected, infections
identified, and chemical analysis can direct further
investigations.

Aftercare
An adhesive bandage and perhaps a single stitch
close the hole. Nothing more is required.

Risks
Risks are negligible. It is remotely possible that an
organ could be punctured and bleed or that an infection could be introduced.

Normal results
A diagnosis of the cause and/or relief from accumulated fluid pressure are the expected results.

Abnormal results
Fluid will continue to accumulate until the cause
is corrected. Repeat procedures may be needed.

The chain of nerve cells that runs from the brain
through the spinal cord out to the muscle is called the
motor pathway. Normal muscle function requires
intact connections all along this motor pathway.
Damage at any point reduces the brain’s ability to
control the muscle’s movements. This reduced efficiency causes weakness, also called paresis. Complete
loss of communication prevents any willed movement
at all. This lack of control is called paralysis. Certain
inherited abnormalities in muscle cause periodic
paralysis, in which the weakness comes and goes.
The line between weakness and paralysis is not
absolute. A condition causing weakness may progress
to paralysis. On the other hand, strength may be
restored to a paralyzed limb. Nerve regeneration or
regrowth is one way in which strength can return to a
paralyzed muscle. Paralysis almost always causes a
change in muscle tone. Paralyzed muscle may be flaccid, flabby, and without appreciable tone, or it may be
spastic, tight, and with abnormally high tone that
increases when the muscle is moved.
Paralysis may affect an individual muscle, but it
usually affects an entire body region. The distribution
of weakness is an important clue to the location of the
nerve damage that is causing the paralysis. Words
describing the distribution of paralysis use the suffix
‘‘-plegia,’’ from the Greek word for ‘‘stroke.’’ The
types of paralysis are classified by region:


monoplegia, affecting only one limb



diplegia, affecting the same body region on both
sides of the body (both arms, for example, or both
sides of the face)



hemiplegia, affecting one side of the body



paraplegia, affecting both legs and the trunk



quadriplegia, affecting all four limbs and the trunk

Resources
BOOKS

Glickman, Robert M. ‘‘Abdominal Swelling and Ascites.’’
In Harrison’s Principles of Internal Medicine, edited by
Anthony S. Fauci, et al. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Paracoccidioidomycosis see South
American blastomycosis

Causes and symptoms
Causes

Paragonamiasis see Fluke infections

The nerve damage that causes paralysis may be in
the brain or spinal cord (the central nervous system) or
it may be in the nerves outside the spinal cord (the

GALE ENCYCLOPEDIA OF MEDICINE

2787

Paralysis

peripheral nervous system). The most common causes
of damage to the brain are:


stroke



tumor



trauma (caused by a fall or a blow)



Multiple sclerosis (a disease that destroys the protective sheath covering nerve cells)



cerebral palsy (a condition caused by a defect or
injury to the brain that occurs at or shortly after
birth)



metabolic disorder (a disorder that interferes with
the body’s ability to maintain itself)

Damage to the spinal cord is most often caused by
trauma, such as a fall or a car crash. Other conditions
that may damage nerves within or immediately adjacent to the spine include:


tumor



herniated disk (also called a ruptured or slipped disk)



spondylosis (a disease that causes stiffness in the
joints of the spine)



rheumatoid arthritis of the spine



neurodegenerative disease (a disease that damages
nerve cells)



multiple sclerosis
Damage to peripheral nerves may be caused by:



trauma



compression or entrapment (such as carpal tunnel
syndrome)



Guillain-Barré syndrome (a disease of the nerves that
sometimes follows fever caused by a viral infection or
immunization)



chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (a condition that causes pain
and swelling in the protective sheath covering nerve
cells)



radiation



inherited demyelinating disease (a condition that
destroys the protective sheath around the nerve cell)



toxins or poisons
Symptoms

The distribution of paralysis offers important
clues to the site of nerve damage. Hemiplegia is almost
always caused by brain damage on the side opposite
the paralysis, often from a stroke. Paraplegia occurs
after injury to the lower spinal cord, and quadriplegia
2788

occurs after damage to the upper spinal cord at the
level of the shoulders or higher (the nerves controlling
the arms leave the spine at that level). Diplegia usually
indicates brain damage, most often from cerebral
palsy. Monoplegia may be caused by isolated damage
to either the central or the peripheral nervous system.
Weakness or paralysis that occurs only in the arms and
legs may indicate demyelinating disease. Fluctuating
symptoms in different parts of the body may be caused
by multiple sclerosis.
Sudden paralysis is most often caused by injury or
stroke. Spreading paralysis may indicate degenerative
disease, inflammatory disease such as Guillain-Barré
syndrome or CIDP, metabolic disorders, or inherited
demyelinating disease.
Other symptoms often accompany paralysis from
any cause. These symptoms may include numbness
and tingling, pain, changes in vision, difficulties with
speech, or problems with balance. Spinal cord injury
often causes loss of function in the bladder, bowel, and
sexual organs. High spinal cord injuries may cause
difficulties in breathing.

Diagnosis
Careful attention should be paid to any events in
the patient’s history that might reveal the cause of the
paralysis. The examiner should look for incidents such
as falls or other traumas, exposure to toxins, recent
infections or surgery, unexplained headache, preexisting metabolic disease, and family history of weakness
or other neurologic conditions. A neurologic examination tests strength, reflexes, and sensation in the
affected area and normal areas.
Imaging studies, including computed tomography
scans (CT scans), magnetic resonance imaging (MRI)
scans, or myelography may reveal the site of the injury.
Electromyography and nerve conduction velocity tests
are performed to test the function of the muscles and
peripheral nerves.

Treatment
The only treatment for paralysis is to treat its
underlying cause. The loss of function caused by longterm paralysis can be treated through a comprehensive
rehabilitation program. Rehabilitation includes:


Physical therapy. The physical therapist focuses on
mobility. Physical therapy helps develop strategies to
compensate for paralysis by using those muscles that
still have normal function, helps maintain and build
any strength and control that remain in the affected
muscles, and helps maintain range of motion in the
GALE ENCYCLOPEDIA OF MEDICINE

Computed tomography (CT)—An imaging technique in which cross-sectional x rays of the body are
compiled to create a three-dimensional image of
the body’s internal structures.
Electromyography—A test that uses electrodes to
record the electrical activity of muscle. The information gathered is used to diagnose neuromuscular
disorders.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Myelin—The insulation covering nerve cells.
Demyelinating disease causes a breakdown of
myelin.
Myelography—An x-ray process that uses a dye or
contrast medium injected into the space around the
spine.
Nerve conduction velocity test—A test that measures the time it takes a nerve impulse to travel a
specific distance over the nerve after electronic
stimulation.

Prevention of paralysis depends on prevention of
the underlying causes. Risk of stroke can be reduced
by controlling high blood pressure and cholesterol
levels. Seatbelts, air bags, and helmets reduce the risk
of injury from motor vehicle accidents and falls. Good
prenatal care can help prevent premature birth, which
is a common cause of cerebral palsy.
Resources
BOOKS

Bradley, Walter G., et al., editors. Neurology in
Clinical Practice. 2nd ed. Boston: ButterworthHeinemann, 1996.

Richard Robinson

Paralysis agitans see Parkinson’s disease
Paralytic shellfish poisoning see Fish and
shellfish poisoning

Paranoia
Definition

affected limbs to prevent muscles from shortening
(contracture) and becoming deformed. If nerve
regrowth is expected, physical therapy is used to
retrain affected limbs during recovery. A physical
therapist also suggests adaptive equipment such as
braces, canes, or wheelchairs.




Occupational therapy. The occupational therapist
focuses on daily activities such as eating and bathing.
Occupational therapy develops special tools and
techniques that permit self-care and suggests ways
to modify the home and workplace so that a patient
with an impairment may live a normal life.
Other specialties. The nature of the impairment may
mean that the patient needs the services of a respiratory therapist, vocational rehabilitation counselor,
social worker, speech-language pathologist, nutritionist, special education teacher, recreation therapist, or clinical psychologist.

Prognosis
The likelihood of recovery from paralysis depends
on what is causing it and how much damage has been
done to the nervous system.
GALE ENCYCLOPEDIA OF MEDICINE

Paranoia is an unfounded or exaggerated distrust
of others, sometimes reaching delusional proportions.
Paranoid individuals constantly suspect the motives
of those around them, and believe that certain individuals, or people in general, are ‘‘out to get them.’’

Description
Paranoid perceptions and behavior may appear as
features of a number of mental illnesses, including
depression and dementia, but are most prominent in
three types of psychological disorders: paranoid schizophrenia, delusional disorder (persecutory type), and
paranoid personality disorder (PPD).
Individuals with paranoid schizophrenia and
persecutory delusional disorder experience what is
known as persecutory delusions: an irrational, yet
unshakable, belief that someone is plotting against
them. Persecutory delusions in paranoid schizophrenia are bizarre, sometimes grandiose, and often
accompanied by auditory hallucinations. Delusions
experienced by individuals with delusional disorder
are more plausible than those experienced by paranoid
schizophrenics; not bizarre, though still unjustified.
Individuals with delusional disorder may seem offbeat
2789

Paranoia

Prevention

KEY TERMS

Paranoia

or quirky rather than mentally ill, and, as such, may
never seek treatment.
Persons with paranoid personality disorder tend
to be self-centered, self-important, defensive, and
emotionally distant. Their paranoia manifests itself
in constant suspicions rather than full-blown delusions. The disorder often impedes social and personal
relationships and career advancement. Some individuals with PPD are described as ‘‘litigious,’’ as they
are constantly initiating frivolous law suits. PPD is
more common in men than in women, and typically
begins in early adulthood.

Causes and symptoms
The exact cause of paranoia is unknown. Potential
causal factors may be genetics, neurological abnormalities, changes in brain chemistry, and stress. Paranoia is
also a possible side effect of drug use and abuse (for
example, alcohol, marijuana, amphetamines, cocaine,
PCP). Acute, or short term, paranoia may occur in
some individuals overwhelmed by stress.
The Diagnostic and Statistical Manual of Mental
Disorders, fourth edition (DSM-IV), the diagnostic
standard for mental health professionals in the
United States, lists the following symptoms for paranoid personality disorder:


suspicious; unfounded suspicions; believes others are
plotting against him/her



preoccupied with unsupported doubts about friends
or associates



reluctant to confide in others due to a fear that
information may be used against him/her



reads negative meanings into innocuous remarks



bears grudges



perceives attacks on his/her reputation that are not
clear to others, and is quick to counterattack



maintains unfounded suspicions regarding the fidelity of a spouse or significant other

Diagnosis
Patients with paranoid symptoms should undergo
a thorough physical examination and patient history
to rule out possible organic causes (such as dementia)
or environmental causes (such as extreme stress). If a
psychological cause is suspected, a psychologist will
conduct an interview with the patient and may administer one of several clinical inventories, or tests, to
evaluate mental status.
2790

KEY TERMS
Persecutory delusion—A fixed, false, and inflexible
belief that others are engaging in a plot or plan to
harm an individual.

Treatment
Paranoia that is symptomatic of paranoid schizophrenia, delusional disorder, or paranoid personality disorder should be treated by a psychologist
and/or psychiatrist. Antipsychotic medication such
as thioridazine (Mellaril), haloperidol (Haldol),
chlorpromazine (Thorazine), clozapine (Clozaril),
or risperidone (Risperdal) may be prescribed, and
cognitive therapy or psychotherapy may be employed
to help the patient cope with their paranoia and/or
persecutory delusions. Antipsychotic medication,
however, is of uncertain benefit to individuals with
paranoid personality disorder and may pose longterm risks.
If an underlying condition, such as depression or
drug abuse, is found to be triggering the paranoia, an
appropriate course of medication and/or psychosocial
therapy is employed to treat the primary disorder.

Prognosis
Because of the inherent mistrust felt by paranoid
individuals, they often must be coerced into entering
treatment. As unwilling participants, their recovery
may be hampered by efforts to sabotage treatment
(for example, not taking medication or not being
forthcoming with a therapist), a lack of insight into
their condition, or the belief that the therapist is plotting against them. Albeit with restricted lifestyles,
some patients with PPD or persecutory delusional
disorder continue to function in society without
treatment.
Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington, DC 20005. (888) 357-7924.
<http://www.psych.org>.
American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Paula Anne Ford-Martin

Parapharyngeal abscess see Abscess

of the constant stimulation of the parathyroid, CRF
patients have high PTH and normal or slightly low
calcium levels.
Tertiary hyperparathyroidism occurs when CRF
causes a severe imbalance in the calcium-phosphate
ratio, leading to very high PTH production that results
in hypercalcemia. Patients with this condition have
high PTH and high calcium levels.

Paraphilias see Sexual perversions
Paraplegia see Paralysis
Parasomnia see Sleep disorders
Parathyroid gland removal see
Parathyroidectomy

Parathyroid hormone test
Definition
The parathyroid hormone (PTH) test is a blood
test performed to determine the serum levels of a
hormone secreted by the parathyroid gland in
response to low blood calcium levels. PTH works
together with vitamin D to maintain healthy bones.
The parathyroid glands are small paired glands
located near the thyroid gland at the base of the neck.

Purpose
The PTH level is measured to evaluate the level of
blood calcium. It is routinely monitored in patients
with a kidney disorder called chronic renal failure
(CRF). Because PTH is one of the major factors
affecting calcium metabolism, the PTH test helps to
distinguish nonparathyroid from parathyroid causes
of too much calcium in the blood (hypercalcemia).
Differential diagnosis of hyperparathyroidism
PTH is also useful in the differential diagnosis of
overactive parathyroid glands (hyperparathyroidism).
Primary hyperparathyroidism is most often caused by a
benign tumor in one or more of the parathyroid
glands. It is rarely caused by parathyroid cancer.
Patients with this condition have high PTH and
calcium levels.
Secondary hyperparathyroidism is often seen in
patients with chronic renal failure (CRF). The kidneys
fail to excrete sufficient phosphate, and the parathyroid gland secretes PTH in an effort to lower calcium
levels to balance the calcium-phosphate ratio. Because
GALE ENCYCLOPEDIA OF MEDICINE

Specific PTH assays
PTH is broken down in the body into three different molecular forms: the intact PTH molecule and
several smaller fragments which include an amino
acid or N-terminal, a midregion or midmolecule, and
a carboxyl or C-terminal. Two tests are currently used
to measure intact PTH and its terminal fragments.
While both tests are used to diagnose hyper-or hypoparathyroidism, each test also has specific applications
as well. The C-terminal PTH assay is used to diagnose
the ongoing disturbances in PTH metabolism that
occur with secondary and tertiary hyperparathyroidism. The assay for intact PTH and the N-terminal
fragment, which are both measured at the same time,
is more accurate in detecting sudden changes in the
PTH level. For this reason, the N-terminal PTH assay
is used to monitor a patient’s response to therapy.

Precautions
Drug interactions
Some prescription drugs affect the results of PTH
tests. Drugs that increase PTH levels include phosphates, anticonvulsants, steroids, isoniazid, lithium,
and rifampin. Drugs that decrease PTH include cimetidine and propranolol.
Timing
PTH levels are subject to daily variation, ranging
from a peak around 2:00 A.M. to a low point around
2:00 P.M. Specimens are usually drawn at 8:00 A.M. The
laboratory should be notified if the patient works a
night shift so that this difference in biological rhythm
can be taken into account.
Other serum level tests
Due to the relationship between PTH and calcium, calcium levels should be tested at the same
time as PTH. Most laboratories have established reference values to indicate what PTH level is normal for a
particular calcium level. In addition, the effects of
PTH on kidney function and bone strength indicate
2791

Parathyroid hormone test

National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Parathyroid scan

KEY TERMS
Assay—An analysis of the chemical composition or
strength of a substance.
Hypercalcemia—Abnormally high levels of blood
calcium.
Hyperparathyroidism—Overactivity of the parathyroid glands. Symptoms include generalized
aches and pains, depression, and abdominal pain.
Hypoparathyroidism—Insufficient production of
parathyroid hormone, which results in low levels
of blood calcium.

that serum calcium, phosphorus, and creatinine levels
should be measured together with PTH. The creatinine
test measures kidney function and aids in the diagnosis
of parathyroid dysfunction.

Description
The PTH test is performed on a sample of the
patient’s blood, withdrawn from a vein into a vacuum
tube. The procedure, which is called a venipuncture,
takes about five minutes.

Preparation
The patient should have nothing to eat or drink
from midnight of the day of the test.

Risks
Risks for this test are minimal, but may include
slight bleeding from the puncture site, a small bruise or
swelling in the area, or fainting or feeling lightheaded.

Normal results
Reference ranges for PTH tests vary somewhat
depending on the laboratory, and must be interpreted
in association with calcium results. The following
ranges are typical:


Intact PTH: 10–65 pg/mL



PTH N-terminal (includes intact PTH): 8–24 pg/mL



PTH C-terminal (includes C-terminal, intact PTH,
and midmolecule): 50–330 pg/mL.

Abnormal results
When measured with serum calcium levels, abnormally high PTH values may indicate primary,
2792

secondary, or tertiary hyperparathyroidism, chronic
renal failure, malabsorption syndrome, and vitamin D
deficiency. Abnormally low PTH levels may indicate
hypoparathyroidism, hypercalcemia, and certain
malignancies.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Parathyroid scan
Definition
A parathyroid scan is sometimes called a parathyroid localization scan or parathyroid scintigraphy.
This scan uses radioactive pharmaceuticals that are
readily taken up by cells in the parathyroid glands to
obtain an image of the glands and any abnormally
active areas within them.

Purpose
The parathyroid glands, embedded in the thyroid
gland in the neck, but separate from the thyroid in
function, control calcium metabolism in the body.
The parathyroid glands produce parathyroid hormone
(PTH). PTH regulates the level of calcium in the blood.
Calcium is critical to cellular metabolism, as well as
being the main component of bones. If too much PTH
is secreted, the bones release calcium into the bloodstream. Over time, the bones become brittle and more
likely to break. A person with levels of calcium in the
blood that are too high feels tired, run down, irritable,
and has difficulty sleeping. Additional signs of too
much calcium in the blood are nausea and vomiting,
frequent urination, kidney stones and bone pain. A
parathyroid scan is administered when the parathyroid
appears to be overactive and a tumor is suspected.

Precautions
Parathyroid scans are not recommended for pregnant women because of the potential harm to the developing fetus. People who have had another recent
nuclear medicine procedure or an intravenous contrast
test may need to wait until the earlier radioactive
GALE ENCYCLOPEDIA OF MEDICINE

Parathyroid scan
The parathyroid glands, embedded in the thyroid gland in the neck but separate from the thyroid gland in function, control
calcium metabolism in the body by producing parathyroid hormone, or PTH. (Custom Medical Stock Photo. Reproduced by
permission.)

markers have been eliminated from their system in order
to obtain accurate results from the parathyroid scan.

Description
A parathyroid scan is a non-invasive procedure
that uses two radiopharmaceuticals (drugs with a
radioactive marker) to obtain an image of highly
active areas of the parathyroid glands. The test can
be done in two ways.
Immediate scan
If the test is to be performed immediately, the
patient lies down on an imaging table with his head
and neck extended and immobilized. The patient is
injected with the first radiopharmaceutical. After waiting 20 minutes, the patient is positioned under the
camera for imaging. Each image takes five minutes. It
is essential that the patient remain still during imaging.
After the first image, the patient is injected with a
second radiopharmaceutical, and imaging continues
for another 25 minutes. Total time for the test is
about one hour: injection 10 minutes, waiting period
20 minutes, and imaging 30 minutes.
Another way to do this test is as follows. After the
first images are acquired, the patient returns two hours
later for additional images. Time for this procedure totals
about three hours: injection 10 minutes, waiting period
two hours and 20 minutes, and imaging 30 minutes.
Delayed scan
In a delayed parathyroid scan, the patient is
asked to swallow capsules containing the first
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cyst—An abnormal sac containing fluid or semisolid material.
Goiter—Chronic enlargement of the thyroid gland.
Neoplasm—An uncontrolled growth of new tissue.

radiopharmaceutical. The patient returns after a
four hour waiting period, and the initial image is
made. Then the patient is injected with the second
radiopharmaceutical. Imaging continues for another
25 minutes. The total time is about four hours and
40 minutes: waiting period four hours, injection 10
minutes, and imaging 30 minutes.

Preparation
No special preparations are necessary for this test.
It is not necessary to fast or maintain a special diet.
The patient should wear comfortable clothing and no
metal jewelry around the neck.

Aftercare
The patient should not feel any adverse effects of
the test and can resume normal activities immediately.

Risks
The only risk associated with this test is to the
fetus of a pregnant woman.
2793

Parathyroidectomy

Normal results
Normal results will show no unusual activity in
the parathyroid glands.

Abnormal results
A concentration of radioactive materials in the
parathyroid gland beyond background levels suggests
excessive activity and the presence of a tumor. False
positive results sometimes result from the presence of
multinodular goiter, neoplasm, or cysts. False positive
tests are tests that interpret the results as abnormal
when this is not true.
Resources
OTHER

‘‘Parathyroid Scan.’’ HealthGate Page. June 13, 1998.
<http://www.healthgate.com>.

Tish Davidson, A.M.

hospital. The operation begins when the anesthesiologist anesthetizes or puts the patient to sleep. The surgeon makes an incision in the front of the neck where a
tight-fitting necklace would rest. All of the parathyroid glands are identified. The surgeon then identifies
the gland or glands with the disease and confirms the
diagnosis by sending a piece of the gland(s) to the
pathology department for immediate microscopic
examination. The glands are then removed and the
incision is closed and a dressing is placed over the
incision.
Patients generally stay overnight in the hospital
after completion of the operation and may remain for
one or two additional days. These procedures are
reimbursed by insurance companies. Surgeon’s fees
typically range from $1,000–$2,000. Anesthesiologists
charge for their services based on the medical status
of the patient and the length of the operative procedure. Hospitals charge for use of the operating
suite, equipment, lab and diagnostic tests, and
medications.

Preparation

Parathyroidectomy
Definition
Parathyroidectomy is the removal of one or
more of the parathyroid glands. The parathyroid
glands are usually four in number, although the
exact number may vary from three to seven. They
are located in the neck in front of the Adam’s apple
and are closely linked to the thyroid gland. The
parathyroid glands regulate the balance of calcium
in the body.

Purpose
Parathyroidectomy is usually done to treat hyperparathyroidism (abnormal over-functioning of the
parathyroid glands).

Precautions
Parathyroidectomy should only be done when
other non-operative methods have failed to control
the patient’s hyperparathyroidism.

Description
Parathyroidectomy is an operation done most
commonly by a general surgeon, or occasionally by
an otolaryngologist, in the operating room of a
2794

Prior to the operation, the diagnosis of hyperparathyroidism should be confirmed using lab tests.
Occasionally, physicians order computed tomography
scans (CT scans), ultrasound exams, and/or magnetic
resonance imaging (MRI) tests to determine the total
number of parathyroid glands and their location prior
to the procedure.

Aftercare
The incision should be watched for signs of infection. In general, no specific wound care is required.
The level of calcium in the body should be monitored during the first 48 hours after the operation by
obtaining frequent blood samples for laboratory
analysis.

Risks
The major risk of parathyroidectomy is injury to
the recurrent laryngeal nerve (a nerve that lies very
near the parathyroid glands and serves the larynx or
voice box). If this nerve is injured, the voice may
become hoarse or weak.
Occasionally, too much parathyroid tissue is
removed, and the patient may develop hypoparathyroidism (under-functioning of the parathyroid glands).
If this occurs, the patient will require daily calcium
supplements.
GALE ENCYCLOPEDIA OF MEDICINE

Anesthesiologist—A physician who specializes in
anesthetizing patients for operations.
Ectopic parathyroid tissue—A condition where the
thyroid tissue is located in an abnormal place.

Thyroid gland

Hyperparathyroidism—Abnormal over-functioning
of the parathyroid glands.
Hypoparathyroidism—Abnormal under-functioning
of the parathyroid glands.

Superior
thyroid glands

Otolaryngologist—A surgeon who treats people
with abnormalities in the head and neck regions
of the body.

Resources

Inferior
thyroid glands

OTHER

‘‘Parathyroidectomy.’’ ThriveOnline.
<http://thriveonline.oxygen.com>.

Trachea
Mary Jeanne Krob, MD, FACS
Parathyroidectomy refers to the surgical removal of one or
more of the parathyroid glands due to hyperparathyroidism
(an abnormal over-functioning of the parathyroid glands). It is
usually done after other non-operative methods have failed to
control or correct this condition. (Illustration by Electronic
Illustrators Group.)

Paratyphoid fever
Sometimes not all of the parathyroid glands are
found in the initial operation. A fifth or sixth gland
may be located in an aberrant location such as the
chest (ectopic parathroid). If this occurs, the patient’s
hyperparathyroidism may not be corrected, and a
second procedure may be required to find the other
gland(s).
Hematoma formation (collection of blood under
the incision) is a possible complication of any operative procedure. However, in procedures that involve
the neck it is of particular concern, because a rapidly
enlarging hematoma can obstruct the airway.
Infection of the surgical incision may occur, as
with any operative procedure, but this is not common.

Normal results
Most patients require only two or three days of
hospitalization to recover from the operation. They
usually can resume most of their normal activities
within one to two weeks.
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Paratyphoid fever, which is sometimes called
Salmonella paratyphi infection, is a serious contagious
disease caused by a gram-negative bacterium. It is also
grouped together with typhoid fever under the name
enteric fever.

Description
Enteric fever is increasingly rare in the United
States. Of the 500 cases reported in an average year,
about 60% are infections acquired during travel in
Mexico, India, or South America.
Paratyphoid fever has three stages: an early stage
marked by high fever; a toxic stage with abdominal
pain and intestinal symptoms, and a long period of
recovery from fever (defervescence). In adults, these
three phases may cover a period of four to six weeks; in
children, they are shorter and may cover 10 days to
two weeks. During the toxic stage there is a 1–10%
chance of intestinal perforation or hemorrhage.
2795

Paratyphoid fever

KEY TERMS

Thyroid cartilage

Paratyphoid fever

Causes and symptoms
Paratyphoid fever is caused by any of three strains
of Salmonella paratyphi: S. paratyphi A; S. schottmuelleri (also called S. paratyphi C); or S. hirschfeldii (also
called S. paratyphi B). It can be transmitted from
animals or animal products to humans or from person
to person. The incubation period is one to two weeks
but is often shorter in children. Symptom onset may be
gradual in adults but is often sudden in children.
Paratyphoid fever is marked by high fever, headache, loss of appetite, vomiting, and constipation or
diarrhea. The patient typically develops an enlarged
spleen. About 30% of patients have rose spots on the
front of the chest during the first week of illness. The
rose spots develop into small hemorrhages that may be
hard to see in African or Native Americans.
Patients with intestinal complications have symptoms resembling those of appendicitis: intense cramping pain with soreness in the right lower quadrant of
the abdomen.

Diagnosis
The diagnosis is usually made on the basis of a
history of recent travel and culturing the paratyphoid
organism. Because the disease is unusual in the
United States, the doctor may not consider paratyphoid in the diagnosis unless the patient has the
classic symptoms of an enlarged spleen and rose
spots. The doctor will need to rule out other diseases
with high fevers, including typhus, brucellosis, tularemia (rabbit fever), psittacosis (parrot fever), mononucleosis, and Kawasaki syndrome. S. paratyphi is
easily cultured from samples of blood, stool, urine, or
bone marrow.

KEY TERMS
Defervescence—Return to normal body temperature after high fever.
Enteric fever—A term that is sometimes used for
either typhoid or paratyphoid fever.
Rose spots—Small slightly raised reddish pimples
that are a distinguishing feature of typhoid or paratyphoid infection.

Supportive care
Patients with paratyphoid fever need careful monitoring for signs of complications as well as bed rest
and nutritional support. Patients with severe infections may require fluid replacement or blood
transfusions.

Prognosis
Most patients with paratyphoid fever recover
completely, although intestinal complications can
result in death. With early treatment, the mortality
rate is less than 1%.

Prevention
Immunization
Vaccination against paratyphoid fever is not
necessary within the United States but is recommended for travel to countries with high rates of
enteric fever.

Treatment
Medications
Paratyphoid fever is treated with antibiotics over
a two- to three-week period with trimethoprimsulfamethoxazole (Bactrim, Septra); amoxicillin
(Amoxil, Novamoxin); and ampicillin (Amcill). Thirdgeneration cephalosporins (ceftriaxone [Rocephin],
cefotaxime [Claforan], or cefixime [Suprax]) or chloramphenicol (Chloromycetin) may be given if the
specific strain is resistant to other antibiotics.
Surgery
Patients with intestinal perforation or hemorrhage may need surgery if the infection cannot be
controlled by antibiotics.
2796

Hygienic measures
Travelers in countries with high rates of paratyphoid fever should be careful to wash hands before
eating and to avoid meat, egg, or poultry dishes unless
they have been thoroughly cooked.
Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

Rebecca J. Frey, PhD

Paresthesias see Numbness and tingling
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Parkinson disease (PD) is a progressive movement
disorder marked by tremors, rigidity, slow movements
(bradykinesia), and posture instability. It occurs when
cells in one of the movement-control centers of the
brain begin to die for unknown reasons. PD was first
noted by British physician James Parkinson in the
early 1800s.

Description
Usually beginning in a person’s late fifties or early
sixties, Parkinson disease causes a progressive decline
in movement control, affecting the ability to control
initiation, speed, and smoothness of motion.
Symptoms of PD are seen in up to 15% of those ages
65–74, and almost 30% of those ages 75–84.
Most cases of PD are sporadic. This means that
there is a spontaneous and permanent change in
nucleotide sequences (the building blocks of genes).
Sporadic mutations also involve unknown environmental factors in combination with genetic defects.
The abnormal gene (mutated gene) will form an
altered end-product or protein. This will cause
abnormalities in specific areas in the body where the
protein is used. Some evidence suggests that the disease is transmitted by autosomal dominant inheritance. This implies that an affected parent has a 50%
chance of transmitting the disease to any child. This
type of inheritance is not commonly observed. The
most recent evidence is linking PD with a gene that
codes for a protein called alpha-synuclein. Further
research is attempting to fully understand the relationship with this protein and nerve cell degeneration.

The substantia nigra, or ‘‘black substance,’’ is one
of the principal movement control centers in the brain.
By releasing the neurotransmitter known as dopamine, it helps to refine movement patterns throughout
the body. The dopamine released by nerve cells of
substantia nigra stimulates another brain region, the
corpus striatum. Without enough dopamine, the corpus striatum cannot control its targets, and so on
down the line. Ultimately, the movement patterns of
walking, writing, reaching for objects, and other basic
programs cannot operate properly, and the symptoms
of parkinsonism are the result.
There are some known toxins that can cause parkinsonism, most notoriously a chemical called MPTP,
found as an impurity in some illegal drugs.
Parkinsonian symptoms appear within hours of ingestion, and are permanent. MPTP may exert its effects
through generation of toxic molecular fragments
called free radicals, and reducing free radicals has
been a target of several experimental treatments for
PD using antioxidants.
It is possible that early exposure to some as-yetunidentified environmental toxin or virus leads to
undetected nigral cell death, and PD then manifests
as normal age-related decline brings the number of
functioning nigral cells below the threshold needed
for normal movement. It is also possible that, for
genetic reasons, some people are simply born with
fewer cells in their substantia nigra than others, and
they develop PD as a consequence of normal decline.

PD affects approximately 500,000 people in the
United States, both men and women, with as many as
50,000 new cases each year.

Symptoms
The identifying symptoms of PD include:

Causes and symptoms
The immediate cause of PD is degeneration of
brain cells in the area known as the substantia nigra,
one of the movement control centers of the brain.
Damage to this area leads to the cluster of symptoms
known as ‘‘parkinsonism.’’ In PD, degenerating brain
cells contain Lewy bodies, which help identify the
disease. The cell death leading to parkinsonism may
be caused by a number of conditions, including infection, trauma, and poisoning. Some drugs given for
psychosis, such as haloperidol (Haldol) or
GALE ENCYCLOPEDIA OF MEDICINE



Tremors, usually beginning in the hands, often
occuring on one side before the other. The classic
tremor of PD is called a ‘‘pill-rolling tremor,’’
because the movement resembles rolling a pill
between the thumb and forefinger. This tremor
occurs at a frequency of about three per second.



Slow movements (bradykinesia) occur, which may
involve slowing down or stopping in the middle of
familiar tasks such as walking, eating, or shaving.
This may include freezing in place during movements
(akinesia).
2797

Parkinson disease

Parkinson disease

chlorpromazine (thorazine), may cause parkinsonism.
When no cause for nigral cell degeneration can be
found, the disorder is called idiopathic parkinsonism,
or Parkinson disease. Parkinsonism may be seen in
other degenerative conditions, known as the ‘‘parkinsonism plus’’ syndromes, such as progressive supranuclear palsy.

Parkinson disease



Muscle rigidity or stiffness, occuring with jerky
movements replacing smooth motion.

compensation and techniques to stimulate movement
during slowdowns or freezes.



Postural instability or balance difficulty occurs. This
may lead to a rapid, shuffling gait (festination) to
prevent falling.



In most cases, there is a ‘‘masked face,’’ with little
facial expression and decreased eye-blinking.

Good nutrition is important to maintenance of
general health. A person with PD may lose some interest in food, especially if depressed, and may have
nausea from the disease or from medications, especially those known as dopamine agonists. Slow movements may make it difficult to eat quickly, and delayed
gastric emptying may lead to a feeling of fullness without having eaten much. Increasing fiber in the diet can
improve constipation, soft foods can reduce the
amount of needed chewing, and a prokinetic drug
such as cisapride (Propulsid) can increase the movement of food through the digestive system.

In addition, a wide range of other symptoms may
often be seen, some beginning earlier than others:


depression



speech changes, including rapid speech without
inflection changes



problems with sleep, including restlessness and
nightmares



emotional changes, including fear, irritability, and
insecurity



incontinence



constipation



handwriting changes, with letters becoming smaller
across the page (micrographia)



progressive problems with intellectual function
(dementia)

Diagnosis
The diagnosis of Parkinson disease involves a
careful medical history and a neurological exam to
look for characteristic symptoms. There are no definitive tests for PD, although a variety of lab tests may be
done to rule out other causes of symptoms, especially
if only some of the identifying symptoms are present.
Tests for other causes of parkinsonism may include
brain scans, blood tests, lumbar puncture, and x rays.

Treatment
There is no cure for Parkinson disease. Most
drugs treat the symptoms of the disease only, although
one drug, selegiline (Eldepryl), may slow degeneration
of the substantia nigra.
Exercise, nutrition, and physical therapy
Regular, moderate exercise has been shown to
improve motor function without an increase in medication for a person with PD. Exercise helps maintain
range of motion in stiff muscles, improve circulation,
and stimulate appetite. An exercise program designed
by a physical therapist has the best chance of meeting
the specific needs of the person with PD. A physical
therapist may also suggest strategies for balance
2798

People with PD may need to limit the amount of
protein in their diets. The main drug used to treat PD,
L-dopa, is an amino acid, and is absorbed by the
digestive system by the same transporters that pick
up other amino acids broken down from proteins in
the diet. Limiting protein, under the direction of the
physician or a nutritionist, can improve the absorption
of L-dopa.
No evidence indicates that vitamin or mineral
supplements can have any effect on the disease other
than in the improvement of the patient’s general
health. No antioxidants used to date have shown promise as a treatment except for selegiline, an MAO-B
inhibitor which is discussed in the Drugs section. A
large, carefully controlled study of vitamin E demonstrated that it could not halt disease progression.
Drugs
The pharmacological treatment of Parkinson
disease is complex. While there are a large number
of drugs that can be effective, their effectiveness varies
with the patient, disease progression, and the length
of time the drug has been used. Dose-related side
effects may preclude using the most effective dose, or
require the introduction of a new drug to counteract
them. There are five classes of drugs currently used to
treat PD.
DRUGS THAT REPLACE DOPAMINE. One drug that
helps replace dopamine, levodopa (L-dopa), is the
single most effective treatment for the symptoms of
PD. L-dopa is a derivative of dopamine, and is converted into dopamine by the brain. It may be started
when symptoms begin, or when they become serious
enough to interfere with work or daily living.

L-dopa therapy usually remains effective for five
years or longer. Following this, many patients develop
motor fluctuations, including peak-dose ‘‘dyskinesias’’ (abnormal movements such as tics, twisting, or
GALE ENCYCLOPEDIA OF MEDICINE

too severe in older patients or in patients with
dementia. In addition, anticholinergics rarely work
for very long. They are often prescribed for younger
patients
who
have
predominant
shaking.
Trihexyphenidyl (Artane) is the drug most commonly
prescribed.

ENZYME INHIBITORS. Dopamine is broken down
by several enzyme systems in the brain and elsewhere
in the body, and blocking these enzymes is a key
strategy to prolonging the effect of dopamine. The
two most commonly prescribed forms of L-dopa contain a drug to inhibit the amino acid decarboxylase (an
AADC inhibitor), one type of enzyme that breaks
down dopamine. These combination drugs are
Sinemet (L-dopa plus carbidopa) and Madopar (Ldopa plus benzaseride). Controlled-release formulations also aid in prolonging the effective interval of
an L-dopa dose.

used as an early therapy before L-dopa is begun, and
as an add-on later in the disease. Its anti-parkinsonian
effects are mild, and are not seen in many patients.
Clozapine (Clozaril) is effective especially against
psychiatric symptoms of late PD, including psychosis
and hallucinations.

The enzyme monoamine oxidase B (MAO-B)
inhibitor selegiline may be given as add-on therapy
for L-dopa. Research indicates selegiline may have a
neuroprotective effect, sparing nigral cells from
damage by free radicals. Because of this, and the fact
that it has few side effects, it is also frequently prescribed early in the disease before L-dopa is begun.
Entacapone and tolcapone, two inhibitors of another
enzyme system called catechol-o-methyl transferase
(COMT), may soon reach the market as early studies
suggest that they effectively treat PD symptoms with
fewer motor fluctuations and decreased daily L-dopa
requirements.
DOPAMINE AGONISTS. Dopamine works by stimulating receptors on the surface of corpus striatum
cells. Drugs that also stimulate these cells are called
dopamine agonists, or DAs. DAs may be used before
L-dopa therapy, or added on to avoid requirements
for higher L-dopa doses late in the disease. DAs available in the United States as of early 1998, include
bromocriptine
(Permax,
Parlodel),
pergolide
(Permax), and pramipexole (Mirapex). Two more,
cabergoline (Dostinex) and ropinirole (Requip), are
expected to be approved soon. Other dopamine agonists in use elsewhere include lisuride (Dopergine) and
apomorphine. Side effects of all the DAs are similar to
those of dopamine, plus confusion and hallucinations
at higher doses.
ANTICHOLINERGIC DRUGS. Anticholinergics maintain dopamine balance as levels decrease. However,
the side effects of anticholinergics (dry mouth, constipation, confusion, and blurred vision) are usually

GALE ENCYCLOPEDIA OF MEDICINE

DRUGS
WHOSE
MODE
OF
ACTION
IS
UNCERTAIN. Amantadine (Symmetrel) is sometimes

Surgery
Two surgical procedures are used for treatment
of PD that cannot be controlled adequately with drug
therapy. In PD, a brain structure called the globus
pallidus (GPi) receives excess stimulation from the
corpus striatum. In a pallidotomy, the GPi is
destroyed by heat, delivered by long thin needles
inserted under anesthesia. Electrical stimulation of
the GPi is another way to reduce its action. In this
procedure, fine electrodes are inserted to deliver the
stimulation, which may be adjusted or turned off as
the response dictates. Other regions of the brain may
also be stimulated by electrodes inserted elsewhere.
In most patients, these procedures lead to significant
improvement for some motor symptoms, including
peak-dose dyskinesias. This allows the patient to
receive more L-dopa, since these dyskinesias are
usually what causes an upper limit on the L-dopa
dose.
A third procedure, transplant of fetal nigral cells,
is still highly experimental. Its benefits to date have
been modest, although improvements in technique
and patient selection are likely to change that.

Alternative treatment
Currently, the best treatments for PD involve the
use of conventional drugs such as levodopa.
Alternative therapies, including acupuncture, massage,
and yoga, can help relieve some symptoms of the disease and loosen tight muscles. Alternative practitioners have also applied herbal and dietary
therapies, including amino acid supplementation,
antioxidant (vitamins A, C, E, selenium, and zinc)
therapy, B vitamin supplementation, and calcium
and magnesium supplementation, to the treatment of
PD. Anyone using these therapies in conjunction with
conventional drugs should check with their doctor to
2799

Parkinson disease

restlessness), rapid loss of response after dosing
(known as the ‘‘on-off’’ phenomenon), and unpredictable drug response. Higher doses are usually tried, but
may lead to an increase in dyskinesias. In addition,
side effects of L-dopa include nausea and vomiting, and
low blood pressure upon standing (orthostatic hypotension), which can cause dizziness. These effects
usually lessen after several weeks of therapy.

Parotidectomy

Resources

KEY TERMS
AADC inhibitors—Drugs that block the amino acid
decarboxylase; one type of enzyme that breaks
down dopamine. Also called DC inhibitors, they
include carbidopa and benserazide.
Akinesia—A loss of the ability to move; freezing in
place.
Bradykinesia—Extremely slow movement.
COMT inhibitors—Drugs that block catechol-omethyl transferase, an enzyme that breaks down
dopamine. COMT inhibitors include entacapone
and tolcapone.
Dopamine—A neurochemical made in the brain
that is involved in many brain activities, including
movement and emotion.
Dyskinesia—Impaired ability to make voluntary
movements.
MAO-B inhibitors—Inhibitors of the enzyme
monoamine oxidase B. MAO-B helps break
down dopamine; inhibiting it prolongs the action
of dopamine in the brain. Selegiline is an MAO-B
inhibitor.
Orthostatic hypotension—A sudden decrease in
blood pressure upon sitting up or standing. May
be a side effect of several types of drugs.
Substantia nigra—One of the movement control
centers of the brain.

avoid the possibility of adverse interactions. For
example, vitamin B6 (either as a supplement or from
foods such as whole grains, bananas, beef, fish, liver,
and potatoes) can interfere with the action of L-dopa
when the drug is taken without carbidopa.

ORGANIZATIONS

National Parkinson Foundation. 1501 NW Ninth Ave., Bob
Hope Road, Miami, FL 33136.
<http://www.parkinson.org>.
Parkinson Disease Foundation. 710 West 168th St., New
York, NY 10032. (800) 457-6676.
<http://www.apdaparkinson.com>.
Worldwide Education and Awareness for Movement
Disorders. One Gustave Levy Place, New York, NY
10029. (800) 437-MOV2. <http://www.wemove.org>.
OTHER

AWAKENINGS. <http://www.parkinsonsdisease.com>.

Laith Farid Gulli, M.D.

Parkinsonism see Parkinson disease
Parotid gland removal see Parotidectomy
Parotid gland scan see Salivary gland scan

Parotidectomy
Definition
Parotidectomy is the removal of the parotid
gland, a salivary gland near the ear.

Purpose
The main purpose of parotidectomy is to remove
cancerous tumors in the parotid gland. A number of
tumors can develop in the parotid gland. Many of
these are tumors that have spread from other areas
of the body, entering the parotid gland by way of the
lymphatic system. Among the tumors seen in the parotid gland are lymphoma, melanoma, and squamous
cell carcinoma.

Prognosis
Despite medical treatment, the symptoms of
Parkinson disease worsen over time, and become less
responsive to drug therapy. Late-stage psychiatric
symptoms are often the most troubling, including difficulty sleeping, nightmares, intellectual impairment
(dementia), hallucinations, and loss of contact with
reality (psychosis).

Prevention
There is no known way to prevent Parkinson
disease.
2800

Description
The parotid gland is the largest of the salivary
glands. There are two parotid glands, one on each
side of the face. They lie just in front of the ears and
a duct runs from each to the inside of the cheek. Each
parotid gland has several lobes. Surgery is recommend
as part of the treatment for all cancers in the parotid
gland. Superficial or localized parotidectomy is
recommended by some authorities, unless a lipoma
or Warthin’s tumor is present. One of the advantages
to this approach is that nerves to facial muscles are left
intact. Many facial nerves run through the same area
GALE ENCYCLOPEDIA OF MEDICINE

Parotidectomy

KEY TERMS
Fistula—An abnormal opening or duct through tissue that results from injury, disease, or other
trauma.
Salivary gland—Three pairs of glands that secrete
into the mouth and aid digestion.

as the parotid gland and can be damaged during more
complete parotidectomies. Most authorities recommend total parotidectomy, especially if cancer is
found in both the superficial and deep lobes of the
parotid gland. If the tumor has spread to involve the
facial nerve, the operation is expanded to include parts
of bone behind the ear (mastoid) to remove as much
tumor as possible. Some authorities recommend postsurgery radiation as follow-up treatment for cancer.

A micrograph of a normal human parotid gland. One of the
salivary glands, the parotid consists of acini arranged in
lobes. This image shows a junction between several lobes;
the clear spaces represent the interlobular connective tissue.
The masses of secretory cells produce a watery secretion
which is passed to the intralobular. (Photograph by Astrid and
Hanns-Frieder Michler, Custom Medical Stock Photo.
Reproduced by permission.)

Aftercare
After surgery, the patient will remain in the
hospital for one to three days. The site of incision
will be watched closely for signs of infection and
heavy bleeding (hemorrhage). The incision site
should be kept clean and dry until it is completely
healed. The patient should not wash their hair until
the stitches have been removed. If the patient has
difficulty smiling, winking, or drinking fluids, the
physician should be contacted immediately. These
are signs of facial nerve damage.

Risks
There are a number of complications that follow
parotidectomy. Facial nerve paralysis after minor surgery should be minimal. During surgery, it is possible
to repair cut nerves. After major surgery, a graft is
attempted to restore nerve function to facial muscles.
Salivary fistulas can occur when saliva collects in
the incision site or drains through the incision.
Reoccurrence of cancer is the single most important
consideration for patients who have undergone parotidectomy. Long term survival rates are largely dependent on the tumor types and the stage of tumor
development at the time of the operation.
Other risks include blood clots (hematoma) and
infection. The most common long-term complication
of parotidectomy is redness and sweating in the cheek,
known as Frey’s syndrome. Rarely, paralysis may
extend throughout all the branches of the facial
nervous system.
GALE ENCYCLOPEDIA OF MEDICINE

Parotidectomy is a surgical procedure performed to remove
cancerous tumors in the parotid gland, a salivary gland near
the ear. Among the tumors seen in the parotid gland are
lymphoma, melanoma, and squamous cell carcinoma. The
illustration above shows the facial incision sites for this
procedure. (Illustration by Electronic Illustrators Group.)

Resources
BOOKS

Bentz, M. L. Pediatric Plastic Surgery. Stamford: Appleton
& Lange, 1998.

Mary K. Fyke
2801

Paroxysmal atrial tachycardia

Parotitis, epidemic see Mumps
Paroxetine see Selective serotonin reuptake
inhibitors

KEY TERMS
Premature atrial beat—A beat that occurs before it
would normally be expected.
Supraventricular—A term for an event that occurs
in the upper chambers (atria) of the heart.

Paroxysmal atrial tachycardia
Definition
A period of very rapid and regular heart beats that
begins and ends abruptly. The heart rate is usually
between 160 and 200 beats per minute. This condition
is also known as paroxysmal supraventricular
tachycardia.

Description
The term paroxysmal means that the event begins
suddenly, without warning and ends abruptly. Atrial
tachycardia means that the upper chambers of the
heart are beating abnormally fast. Paroxysmal atrial
tachycardia can occur without any heart disease being
present. It is usually more annoying than dangerous.

Causes and symptoms
Paroxysmal atrial tachycardia may be caused by
several different things. The fast rate may be triggered
by a premature atrial beat that sends an impulse along
an abnormal electrical path to the ventricles. Other
causes stem from anxiety, stimulants, overactive thyroid, and in some women, the onset of menstruation.
Though seldom life-threatening, paroxysmal
atrial tachycardia produces annoying symptoms
which can include lightheadedness, chest pain, palpitations, anxiety, sweating, and shortness of breath.

Diagnosis
Diagnosis is not always easy, because the event is
usually over by the time the patient sees a doctor. A
careful description of the episode will aid the doctor in
his diagnosis. If the rapid heart rate is still occurring, an
electrocardiograph (ECG) will show the condition. If
the event is over, physicians often recommend a period
of ambulatory electrocardiographic monitoring (called
Holter monitoring) to confirm the diagnosis.

Treatment
The doctor may suggest that during an episode of
paroxysmal atrial tachycardia the following practice
2802

may help. Briefly hold the nose and mouth closed and
breathe out, or by bearing down, as though straining
at a bowel movement. The doctor may try to stop the
episode by gently massaging an area in the neck called
the carotid sinus.
If these conservative measures do not work, an
injection of the drug verapamil or adenosine should
stop the episode quickly.
In rare cases, the drugs do not work and electrical
shock (cardioversion) may be necessary, particularly
if serious symptoms are also present with the
tachycardia.

Prognosis
Paroxysmal atrial tachycardia is not a disease, and
is seldom life-threatening. The episodes are usually
more unpleasant than they are dangerous, and the
prognosis is generally good.

Prevention
Frequent episodes are usually cause for medication. In rare cases, the doctor may recommend a procedure called catheter ablation, which will remove (or
ablate) the precise area of the heart responsible for
triggering the fast heart rate.
In a catheter ablation procedure, the doctor will
place a special catheter against the area of the heart
responsible for the problem. Radio-frequency energy
is then passed to the tip of the catheter, so that it heats
up and destroys the target area. Catheter ablation is
considered a non-surgical technique.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave., Dallas,
TX 75231. (214) 373-6300.
<http://www.americanheart.org>.

Dorothy Elinor Stonely

Paroxysmal supraventricular tachycardia see
Paroxysmal atrial tachycardia
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Parrot fever is a rare infectious disease that causes
pneumonia in humans. It is transmitted from pet birds
or poultry. The illness is caused by a chlamydia, which
is a type of intracellular parasite closely related to
bacteria. Parrot fever is also called chlamydiosis, psittacosis, or ornithosis.

Avian chlamydiosis—An illness in pet birds and
poultry caused by Chlamydia psittaci. It is also
known as parrot fever in birds.
Chlamydia psittaci—An organism related to bacteria that infects some types of birds and can be
transmitted to humans to cause parrot fever.
Chlamydiosis, psittacosis, or ornithosis—Other
names for parrot fever in humans.

Description
Parrot fever, which is referred to as avian psittacosis when it infects birds, is caused by Chlamydia
psittaci. Pet birds in the parrot family, including
parrots, parakeets, macaws, and cockatiels, are the
most common carriers of the infection. Other birds
that may also spread C. psittaci include pigeons,
doves, mynah birds, and turkeys. Birds that are carrying the organism may appear healthy, but can shed it
in their feces. The symptoms of avian psittacosis
include inactivity, loss of appetite and ruffled feathers,
diarrhea, runny eyes and nasal discharge, and green or
yellow-green urine. Sick birds can be treated with
antibiotics by a veterinarian.
C. psittaci is usually spread from birds to humans
through exposure to infected bird feces during cage
cleaning or by handling infected birds. In humans,
parrot fever can range in severity from minor flu-like
symptoms to severe and life-threatening pneumonia.

Causes and symptoms
Parrot fever is usually transmitted by inhaling
dust from dried bird droppings or by handling infected
birds. Humans can also spread the disease by personto-person contact, but that is very rare. The symptoms
usually develop within five to 14 days of exposure and
include fever, headache, chills, loss of appetite, cough,
and tiredness. In the most severe cases of parrot fever,
the patient develops pneumonia. People who work in
pet shops or who keep pet birds are the most likely to
become infected.

Diagnosis
Only 100–200 cases of parrot fever are reported
each year in the United States. It is possible, however,
that the illness is more common since it is easily confused with other types of influenza or pneumonia.
Doctors are most likely to consider a diagnosis of
parrot fever if the patient has a recent history of exposure to birds. The diagnosis can be confirmed by blood
GALE ENCYCLOPEDIA OF MEDICINE

tests for antibodies, usually complement fixation or
immunofluorescence tests. The organism is difficult to
culture. A chest x ray may also be used to diagnose the
pneumonia caused by C. psittaci.

Treatment
Psittacosis is treated with an antibiotic, usually
tetracycline (Achromycin, Sumycin); doxycycline
(Doxy, Vibramycin); or erythromycin (Eryc, Ilotycin).
Oral medication is typically prescribed for at least
10–14 days. Severely ill patients may be given intravenous antibiotics for the first few days of therapy.

Prognosis
The prognosis for recovery is excellent; with antibiotic treatment, more than 99% of patients with parrot fever will recover. Severe infections, however, may
be fatal to the elderly, untreated persons, and persons
with weak immune systems.

Prevention
As of 1998, there is no vaccine that is effective
against parrot fever. Birds that are imported into the
country as pets should be quarantined to ensure that
they are not infected before they can be sold. Health
authorities recommend that breeders and importers
feed imported birds a special blend of feed mixed
with antibiotics for 45 days to ensure that any C.
psittaci organisms are destroyed. In addition, bird
cages and food and water bowls should be cleaned
daily.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
2803

Parrot fever

KEY TERMS

Parrot fever

Partial thromboplastin time

OTHER

‘‘Psittacosis (Parrot Fever; Ornithosis).’’ ThriveOnline.
<http://thriveonline.oxygen.com>.

Altha Roberts Edgren

Partial birth abortion see Abortion, partial
birth

Partial thromboplastin time
Definition
The partial thromboplastin time (PTT) test is a
blood test that is done to investigate bleeding disorders and to monitor patients taking an anticlotting
drug (heparin).

Purpose
Diagnosis
Blood clotting (coagulation) depends on the
action of substances in the blood called clotting factors. Measuring the partial thromboplastin time helps
to assess which specific clotting factors may be missing
or defective.
Monitoring
Certain surgical procedures and diseases cause
blood clots to form within blood vessels. Heparin is
used to treat these clots. The PTT test can be used to
monitor the effect of heparin on a patient’s coagulation system.

Precautions
Certain medications besides heparin can affect the
results of the PPT test. These include antihistamines,
vitamin C (ascorbic acid), aspirin, and chlorpromazine
(Thorazine).

and common pathways. It is usually done in combination with other tests, such as the prothrombin test,
which evaluate the factors of the extrinsic pathway.
The combination of tests narrows the list of possible
missing or defective factors.
Heparin prevents clotting by blocking certain factors in the intrinsic pathway. The PTT test allows a
doctor to check that there is enough heparin in the
blood to prevent clotting, but not so much as to cause
bleeding. The test is done before the first dose of
heparin or whenever the dosage level is changed; and
again when the heparin has reached a constant level in
the blood. The PTT test is repeated at scheduled
intervals.
The PTT test uses blood to which a chemical has
been added to prevent clotting before the test begins.
About 5 mL of blood are drawn from a vein in the
patient’s inner elbow region. Collection of the sample
takes only a few minutes. The blood is spun in a
centrifuge, which separates the pale yellow liquid
part of blood (plasma) from the cells. Calcium and
activating substances are added to the plasma to start
the intrinsic pathway of the coagulation cascade. The
partial thromboplastin time is the time it takes for a
clot to form, measured in seconds.
The test can be done without activators, but they
are usually added to shorten the clotting time, making
the test more useful for monitoring heparin levels.
When activators are used, the test is called activated
partial thromboplastin time or APTT.
Test results can be obtained in less than one hour.
The test is usually covered by insurance.

Preparation
The doctor should check to see if the patient is
taking any of the medications that may influence the
test results. If the patient is on heparin therapy, the
blood sample is drawn one hour before the next dose
of heparin.

Aftercare
Description
When a body tissue is injured and begins to bleed,
it starts a sequence of clotting factor activities called
the coagulation cascade, which leads to the formation
of a blood clot. The cascade has three pathways:
extrinsic, intrinsic, and common. Many of the thirteen
known clotting factors in human blood are shared by
both pathways; several are found in only one. The
PTT test evaluates the factors found in the intrinsic
2804

Aftercare includes routine care of the puncture
site. In addition, patients on heparin therapy must be
watched for signs of spontaneous bleeding. The
patient should not be left alone until the doctor or
nurse is sure that bleeding has stopped. Patients
should also be advised to watch for bleeding gums,
bruising easily, and other signs of clotting problems; to
avoid activities that might cause minor cuts or bruises;
and to avoid using aspirin.
GALE ENCYCLOPEDIA OF MEDICINE

Activated partial thromboplastin time—Partial
thromboplastin time test that uses activators to
shorten the clotting time, making it more useful for
heparin monitoring.
Clotting factors—Substances in the blood that act
in sequence to stop bleeding by forming a clot.
Coagulation—The process of blood clotting.
Coagulation cascade—The sequence of biochemical activities, involving clotting factors, that stop
bleeding by forming a clot.
Common pathway—The pathway that results from
the merging of the extrinsic and intrinsic pathways.
The common pathway includes the final steps
before a clot is formed.
Extrinsic pathway—One of three pathways in the
coagulation cascade.
Heparin—A medication that prevents blood clots.
Intrinsic pathway—One of three pathways in the
coagulation cascade.
Partial thromboplastin time—A test that checks the
clotting factors of the intrinsic pathway.
Plasma—The fluid part of blood, as distinguished
from blood cells.

Risks
The patient may develop a bruise or swelling
around the puncture site, which can be treated with
moist warm compresses. People with coagulation problems may bleed for a longer period than normal.

Normal results
Normal results vary based on the method and activators used. Normal APTT results are usually between
25–40 seconds; PTT results are between 60–70 seconds.
APTT results for a patient on heparin should be 1.5–2.5
times normal values. An APTT longer than 100 seconds
indicates spontaneous bleeding.

Low levels in a patient on heparin indicate too
little heparin is in the blood to prevent clots. High
levels indicate too much heparin is present, placing
the person at risk of excessive bleeding.
Resources
PERIODICALS

Berry, Brian R., and Stephen Nantel. ‘‘Heparin Therapy:
Current Regimens and Principles of Monitoring.’’
Postgraduate Medicine 99 (June 1996): 64-76.

Nancy J. Nordenson

Paruresis
Definition
The inability to urinate in the presence of others.

Description
Paruresis, also known as shy or bashful bladder, is
the inability or difficulty to urinate in the presence of
other people, when under time pressure, or on vehicles
such as trains or airplanes. Urination is normal when
those constraints or factors are absent, typically when in
the bathroom at home. Research suggests up to 17 million Americans, 3.25 million Canadians, and 51 million
Europeans suffer from the social anxiety disorder.
Paruresis ranges in intensity from mild, in which the
person can urinate in public facilities under certain circumstances, to severe, in which the person can only
urinate when alone at home. The condition almost exclusively affects males although it can occur in females.
Paruresis can be socially disabling and can often
completely take over a person’s life. Examples include
avoiding travel, social functions, and sports arenas. Just
as serious are the psychological consequences, such as
depression, and anxiety. Job choices and career decisions
are often adversely affected. People with the condition
often avoid jobs where there is mandatory drug testing
done by the supervised collection of a urine sample.

Causes and symptoms
Abnormal results
Increased levels in a person with a bleeding disorder indicate a clotting factor may be missing or
defective. Further tests are done to identify the factor
involved. Liver disease decreases production of factors, increasing the PTT.
GALE ENCYCLOPEDIA OF MEDICINE

Paruretics (people who suffer from paruresis) commonly refer to three triggers that influence them when
in public restrooms. For the typical paruretic, these
triggers must be removed, or the person must try
another toilet, for urination to occur on a particular
occasion. First, the condition occurs much more
2805

Paruresis

KEY TERMS

Paruresis

frequently when strangers are present in the restroom as
opposed to friends or relatives. Second, proximity plays
a role in the problem. Proximity for the paruretic is
both physical, involving the relative closeness of others
in or near the restroom, and psychological, involving
the need for privacy. The most frequent complaint
about physical stimuli in public facilities is the absence
of suitable partitions and doors on urinals or stalls.
Third, temporary psychological states, especially anxiety, anger, and fear can interfere with urination.

Diagnosis
The condition is diagnosed on the basis of the
sufferer’s account of their symptoms. In severe cases,
sufferers can waste considerable time waiting for
everyone else to leave the toilet before they can urinate, and might totally avoid urinating in public toilets. The condition is usually self-diagnosed when any
or all of the three main triggers of paruresis are present
and the condition is chronic.

Treatment
The most well documented current treatment is
based upon cognitive-behavioral therapy, of which the
aim is to reorganize the ‘‘abnormal’’ emotional schemes
arising from the anxiety generating elements that
trigger this problem. This can be done individually in
a self-help situation, in a support group, or through
psychotherapy with a psychologist or psychiatrist.
Therapy includes three separate but linked
components:


Cognitive—An attempt to modify the abnormal
thoughts and ideas around the object of anxiety,
such as the thought, ‘‘When I use a toilet, everybody
looks at me and wonders what I’m doing.’’



Behavioral—Step by step desensitization by very
gradual exposure to the feared situation, the aim
being to achieve a series of small successes, and thus
reassure the subconscious mind that it is ‘‘safe’’ to
urinate in a situation that previously led to panic and
failure. This can be thought of as relearning urination in a social situation.



Relaxation—Learning techniques that facilitate
relaxation, both mental and physical, such as sphincter relaxation exercises.

Drug treatments, usually with medications used to
treat benign prostate hyperplasia (BPH), an enlargement of the prostate gland, such as terazosin (Hytrin),
tamsulosin (Flomax), and alfuzosin (Uroxatral) are the
subject of much debate and usually produce poor
results.
2806

KEY TERMS
Benign prostate hyperplasia (BPH)—Enlargement
of the prostate gland.
Psychotherapy—The treatment of mental disorders
by psychological methods, usually by a psychiatrist
or psychologist.
Sphincter—A circular band of muscle that surrounds an opening or passage in the body and
narrows or closes the opening by contracting.
Urethra—The tube in humans that carries urine
from the bladder out of the body.

Alternative treatment
One possible alternative medicine treatment is saw
palmetto, used to treat urinary problems in men with
BPH, an enlargement of the prostate gland. BPH
results in a swelling of the prostate gland that
obstructs the urethra. This causes painful urination,
reduced urine flow, difficulty starting or stopping the
flow, dribbling after urination, and more frequent
nighttime urination. A typical dose is 320 mg per day
of standardized extract. It may take up to four weeks
of use before beneficial effects are seen.

Prognosis
Most people who suffer from the condition never
seek help or treatment. Many never even discuss the
problem with anyone. But anecdotal evidence suggests
that those who do seek help have a good success rate at
overcoming their fear or anxiety over time, sometimes
a year or longer.

Prevention
There is no known way to prevent a person from
developing paruresis. Anecdotal evidence suggests it
often does not occur until around the age of puberty.
One suggestion for prevention is to condition
children from an early age to urinate in public
restrooms.
Resources
PERIODICALS

Landers, Peter. ‘‘Looking for Relief: Shy Bladder Syndrome
is Widespread; But in Many Cases it Can Be
Treated Successfully.’’ The Wall Street Journal
(April 22, 2003): R5.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

International Paruresis Association. P.O. Box 65111,
Baltimore, MD 21209. (800) 247-3864.
info@paruresis.org. http://www.paruresis.org.
OTHER

June 11, 2001. WebMDThe Secret Social Phobia. http://
my.webmd.com/content/Article/14/1674_51491.htm.
(Accessed March 31, 2005).

Ken R. Wells

Parvovirus B19 infection see Fifth disease
Pasteurellosis see Animal bite infections

Patau syndrome
Definition
Patau syndrome, also called trisomy 13, is a congenital (present at birth) disorder associated with the
presence of an extra copy of chromosome 13. The extra
chromosome 13 causes numerous physical and mental
abnormalities, especially heart defects. Patau syndrome
is named for Dr. Klaus Patau, who reported the syndrome and its association with trisomy in 1960. It is
sometimes called Bartholin-Patau syndrome, named in
part for Thomas Bartholin, a French physician who
described an infant with the syndrome in 1656.

Description
Children normally inherit 23 chromosomes from
each parent, for a total of 46 chromosomes. A typical
human being has 46 chromosomes: 22 pairs of non-sex
linked chromosomes and one pair of sex-linked chromosomes, that determine that child’s sex. Sometimes a
child may end up with more than 46 chromosomes
because of problems with the father’s sperm or the
mother’s egg; or, because of mutations that occurred
after the sperm and the egg fused to form the embryo
(conception).
Normally, there are two copies of each of the
23 chromosomes: one from each parent. A condition
called trisomy occurs when three, instead of two,
copies of a chromosome are present in a developing
human embryo. An extra copy of a particular chromosome can come either from the egg or sperm, or
because of mutations that occur after conception.
GALE ENCYCLOPEDIA OF MEDICINE

The best-known trisomy-related disorder is Down
syndrome (trisomy 21), in which the developing
embryo has an extra copy of chromosome 21. Patau
syndrome is trisomy 13, in which the developing
embryo has three copies of chromosome 13.
An extra copy of chromosome 13 is not the only
cause of Patau syndrome. Other changes in chromosome 13, such as mispositioning (translocation), can
also result in the characteristics classified as Patau
syndrome. In these cases, an error occurs that causes
a portion of chromosome 13 to be exchanged for a
portion of another chromosome. There is no production of extra chromosomes, but a portion of each
affected chromosome is ‘‘misplaced’’ (translocated)
to another chromosome.
Patau syndrome causes serious physical and mental abnormalities including: heart defects; incomplete
brain development; such unusual facial features as
a sloping forehead, a smaller than average head
(microcephaly), small or missing eyes, low-set ears,
and cleft palate or hare lip; extra fingers and toes
(polydactyly); abnormal genitalia; spinal defects;
seizures; gastrointestinal hernias, particularly at the
navel (omphalocele); and mental retardation. Due to
the severity of these conditions, fewer than 20% of
those affected with Patau syndrome survive beyond
infancy. Most infants with the syndrome die within the
first three months of life; the average life expectancy of
the survivors is about 10 years.
Genetic profile
When an extra copy (trisomy) of a chromosome is
made, it may either be a total trisomy (in which an
extra copy of the entire chromosome is made), or
partial trisomy (in which only one part of the chromosome is made an extra time).
In most cases of trisomy, errors in chromosome
duplication occur at conception because of problems
with the egg or the sperm that are coming together to
produce an offspring. In these cases, every cell in the
body of the offspring has an extra copy of the affected
chromosome. However, errors in chromosome duplication may also occur during the rapid cell division
that takes place immediately after conception. In these
cases, only some cells of the body have the extra chromosome error. The condition in which only some of
the cells in the body have the extra chromosome is
called mosaicism.
Seventy-five to 80 percent of the cases of Patau
syndrome are caused by a trisomy of chromosome 13.
Some of these cases are the result of a total trisomy,
while others are the result of a partial trisomy. Partial
2807

Patau syndrome

Siwolop, Sana. ‘‘For Some, Drug Tests Are Almost
Impossible.’’ The New York Times (April 14, 2002): NJ1.

Patau syndrome

trisomy generally causes less severe physical symptoms than full trisomy. Ten percent of these cases are
of the mosaic type, in which only some of the body’s
cells have the extra chromosome. The physical symptoms of the mosaic form of Patau syndrome depends
on the number and type of cells that carry the trisomy.
Most cases of trisomy are not passed on from one
generation to the next. Usually they result from a
malfunction in the cell division (mitosis) that occurs
after conception. At least 75% of the cases of Patau
syndrome are caused by errors in chromosome replication that occur after conception. The remaining
25% are caused by the inheritance of translocations
of chromosome 13 with other chromosomes within the
parental chromosomes. In these cases, a portion of
another chromosome switches places with a portion
of chromosome 13. This leads to errors in the genes on
both chromosome 13 and the chromosome from
which the translocated portion originated.
Patau syndrome occurs in approximately one in
8,000–12,000 live births in the United States. In many
cases, spontaneous abortion (miscarriage) occurs and
the fetus does not survive to term. In other cases, the
affected individual is stillborn. As appears to be the
case in all trisonomies, the risks of Patau syndrome
seem to increase with the mother’s age, particularly if
she is over 30 when pregnant. Male and female children are equally affected, and the syndrome occurs in
all races and ethnic groups. Females with Patau syndrome, however, have a better chance of surviving
past infancy than males.

Causes and symptoms
The severity and symptoms of Patau syndrome
vary with the type of chromosomal anomaly, from
extremely serious conditions to nearly normal appearance and functioning.

defects described above. The eyes may be unusually
small (microphthalmia) or one eye may be absent
(anophthalmia). The eyes are sometimes set close
together (hypotelorism) or even fused into a single
structure. Incomplete development of any structures
in the eye (coloboma) or failure of the retina to
develop properly (retinal dysplasia) will also produce
vision problems. Patau syndrome affected individuals
may be born either partially or totally deaf and many
are subject to recurring ear infections.
The facial features of many Patau syndromeaffected individuals appear flattened. The ears are
generally malformed and lowset. Frequently, a child
with trisomy 13 has a cleft lip, a cleft palate, or both.
Other physical characteristics include loose folds of
skin at the back of the neck, extra fingers or toes
(polydactyly), permanently flexed (closed) fingers
(camptodactyly), noticeably prominent heels,
‘‘rocker-bottom foot,’’ and missing ribs. Genital malformations are common in individuals affected with
Patau syndrome and include undescended testicles
(cryptorchidism), an abnormally developed scrotum,
and ambiguous genitalia in males, or an abnormally
formed uterus (bicornuate uterus) in females.
In nearly all cases, Patau syndrome affected
infants have respiratory difficulties and heart defects,
including atrial and ventricular septal defects (holes
between chambers of the heart); malformed ducts that
cause abnormal direction of blood flow (patent ductus
arteriosus); holes in the valves of the lungs and the
heart (pulmonary and aortic valves); and misplacement of the heart in the right, rather than the left,
side of the chest (dextrocardia). The kidneys and
gastrointestinal system may also be affected with
cysts similar to those seen in polycystic kidney disease.
These defects are frequently severe and lifethreatening.

Full trisomy 13, which is present in the majority of
the cases, results in the most severe and numerous
internal and external abnormalities. Commonly, the
forebrain fails to divide into lobes or hemispheres
(holoprosencephaly) and the entire head is unusually
small (microcephaly). The spinal cord may protrude
through a defect in the vertebrae of the spinal column
(myelomeningocele). Children who survive infancy
have profound mental retardation and may experience
seizures. In a few rare cases Patau syndrome may
coexist with Klinefelter’s syndrome or other chromosomal abnormalities.

Partial trisomy of the distal segment of chromosome 13 results in generally less severe, but still serious, symptoms and a distinctive facial appearance
including a short upturned nose, a longer than usual
area between the nose and upper lip (philtrum), bushy
eyebrows, and tumors made up of blood capillaries on
the forehead (frontal capillary hemangiomata). Partial
trisomy of the proximal segment of chromosome 13 is
much less likely to be fatal and has been associated
with a variety of facial features including a large nose,
a short upper lip, and a receding jaw. Both forms of
partial trisomy also result in severe mental
retardation.

Incomplete development of the optic (sight) and
olfactory (smell) nerves often accompany the brain

Beyond one month of age, other symptoms that
are seen in individuals with Patau syndrome are:

2808

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Patau syndrome is detectable during pregnancy
through the use of ultrasound imaging, amniocentesis,
and chorionic villus sampling (CVS). At birth, the newborn’s numerous malformations indicate a possible
chromosomal abnormality. Trisomy 13 is confirmed
by examining the infant’s chromosomal pattern through
karyotyping or another procedure. Karyotyping
involves the separation and isolation of the chromosomes present in cells taken from an individual. These
cells are generally extracted from cells found in a blood
sample. The 22 non-sex linked chromosomes are identified by size, from largest to smallest, as chromosomes
1 through 22. The sex-determining chromosomes are
also identified. The diagnosis of Patau syndrome is
confirmed by the presence of three, rather than the
normal two, copies of the thirteenth largest
chromosome.
A newer method of diagnosing trisomies that has
the advantages of speed and lower cost is the quantitative fluorescent PCR (QF-PCR) assay. QF-PCR
testing allows a doctor to determine the presence of a
chromosomal abnormality within 24 hours with a very
high degree of accuracy.

Treatment
Some infants born with Patau syndrome have
severe and incurable birth defects. However, children
with better prognoses require medical treatment to
correct structural abnormalities and associated complications. For feeding problems, special formulas,
positions, and techniques may be used. Tube feeding
or the placement of a gastric tube (gastrostomy) may
be required. Structural abnormalities such as cleft lip
and cleft palate can be corrected through surgery.
Special diets, hearing aids, and vision aids can be
used to mitigate the symptoms of Patau syndrome.
Physical therapy, speech therapy, and other types of
developmental therapy will help the child reach his or
her potential.
Since the translocation form of Patau syndrome
is genetically transmitted, genetic counseling for the
parents should be part of the management of the
disease.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Amniocentesis—A procedure performed at 16–18
weeks of pregnancy in which a needle is inserted
through a woman’s abdomen into her uterus to
draw out a small sample of the amniotic fluid from
around the baby. Either the fluid itself or cells from
the fluid can be used for a variety of tests to obtain
information about genetic disorders and other medical conditions in the fetus.
Chorionic villus sampling (CVS)—A procedure
used for prenatal diagnosis at 10–12 weeks gestation. Under ultrasound guidance a needle is inserted
either through the mother’s vagina or abdominal
wall and a sample of cells is collected from around
the fetus. These cells are then tested for chromosome
abnormalities or other genetic diseases.
Chromosome—A microscopic thread-like structure
found within each cell of the body consisting of a
complex of proteins and DNA. Humans have 46
chromosomes arranged into 23 pairs. Changes in
either the total number of chromosomes or their
shape and size (structure) may lead to physical or
mental abnormalities.
Karyotyping—A laboratory procedure in which
chromosomes are separated from cells, stained,
and arranged so that their structure can be studied
under the microscope.
Mosaicism—A genetic condition resulting from a
mutation, crossing over, or nondisjunction of chromosomes during cell division, causing a variation
in the number of chromosomes in the cells.
Translocation—The transfer of one part of a chromosome to another chromosome during cell division. A balanced translocation occurs when pieces
from two different chromosomes exchange places
without loss or gain of any chromosome material.
An unbalanced translocation involves the unequal
loss or gain of genetic information between two
chromosomes.
Trisomy—The condition of having three identical
chromosomes instead of the normal two in a cell.
Ultrasound—An imaging technique that uses
sound waves to help visualize internal structures
in the body.

Prognosis
Approximately 45% of trisomy 13 babies die
within their first month of life; up to 70% in the first
2809

Patau syndrome

feeding difficulties and constipation, reflux disease,
slow growth rates, curvature of the spine (scoliosis),
irritability, sensitivity to sunlight, low muscle tone,
high blood pressure, sinus infections, urinary tract
infections, and ear and eye infections.

Patent ductus arteriosus

six months; and over 70% by one year of age. Survival
to adulthood is very rare. Only one adult is known to
have survived to age 33.
Most survivors have profound mental and physical disabilities; however, the capacity for learning in
children with Patau syndrome varies from case to
case. Older children may be able to walk with or
without a walker. They may also be able to understand words and phrases, follow simple commands,
use a few words or signs, and recognize and interact
with others.

OTHER

Pediatric Database (PEDBASE) Homepage. February 9,
2001. <http://www.icondata.com/health/pedbase/
files/TRISOMY1.HTM>.
‘‘Trisomy 13.’’ WebMD February 9, 2001. <http://
my.webmd.com/content/asset/
adam_disease_trisomy_13>.

Paul A. Johnson, Ed.M.
Rebecca J. Frey, Ph.D.

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Congenital Anomalies.’’ Section 19, Chapter 261. In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Best, Robert G., PhD., and James Stallworth, MD. ‘‘Patau
Syndrome.’’ eMedicine November 21, 2002. <http://
www.emedicine.com/ped/topic1745.htm>.
Cirigliano, V., G. Voglino, M. P. Canadas, et al. ‘‘Rapid
Prenatal Diagnosis of Common Chromosome
Aneuploidies by QF-PCR. Assessment on 18,000
Consecutive Clinical Samples.’’ Molecular Human
Reproduction 10 (November 2004): 839–846.
Mann, K., C. Donaghue, S. P. Fox, et al. ‘‘Strategies for the
Rapid Prenatal Diagnosis of Chromosome
Aneuploidy.’’ European Journal of Human Genetics 12
(November 2004): 907–915.
Oyler, M., B. W. Long, and L. A. Cox. ‘‘Sonographic
Markers Used to Detect Frequent Trisomies.’’
Radiologic Technology 76 (September-October
2004): 13–18.
Rossino, R., and A. L. Nucaro. ‘‘Prenatal Diagnosis of a
Double Trisomy 48, XXY, +13: Klinefelter and Patau
Syndromes.’’ American Journal of Medical Genetics,
Part A 132A (December 15, 2004): 342.
ORGANIZATIONS

National Organization for Rare Disorders (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT
06813-1968. (203) 744-0100. Fax: (203) 798-2291.
<http://www.rarediseases.org>.
Rainbows Down Under—A Trisomy 18 and Trisomy 13
Resource. SOFT Australia, 198 Oak Rd., Kirrawee,
NSW 2232. Australia 02-9521-6039.
<http://members.optushome.com.au/karens>.
Support Organization for Trisomy 18, 13, and Related
Disorders (SOFT). 2982 South Union St., Rochester,
NY 14624. (800) 716-SOFT.
<http://www.trisomy.org>.
2810

Patent ductus arteriosus
Definition
Patent ductus arteriosus (PDA) is a heart defect
that occurs when the ductus arteriosus (the temporary
fetal blood vessel that connects the aorta and the
pulmonary artery) does not close at birth.

Description
The ductus arteriosus is a temporary fetal blood
vessel that connects the aorta and the pulmonary
artery before birth. The ductus arteriosus should be
present and open before birth while the fetus is developing in the uterus. Since oxygen and nutrients are
received from the placenta and the umbilical cord
instead of the lungs, the ductus arteriosus acts as a
‘‘short cut’’ that allows blood to bypass the deflated
lungs and go straight out to the body. After birth,
when the lungs are needed to add oxygen to the
blood, the ductus arteriosus normally closes. The closure of the ductus arteriosus ensures that blood goes to
the lungs to pick up oxygen before going out to the
body. Closure of the ductus arteriosus usually occurs
at birth as levels of certain chemicals, called prostagladins, change and the lungs fill with air. If the ductus
arteriosus closes correctly, the blood pumped from the
heart goes to the lungs, back into the heart, and then
out to the body through the aorta. The blood returning from the lungs and moving out of the aorta carries
oxygen to the cells of the body.
In some infants, the ductus arteriosus remains
open (or patent) and the resulting heart defect is
known as patent ductus arteriosus. In most cases, a
small PDA does not result in physical symptoms. If the
PDA is larger, health complications may occur.
In an average individual’s body, the power of blood
being pumped by the heart and other forces leads to a
certain level of pressure between the heart and lungs.
GALE ENCYCLOPEDIA OF MEDICINE

As noted, the size of the PDA determines how
much harder the heart has to work and how much
bigger the heart becomes. If the PDA is large, the
bottom left side of the heart is forced to pump twice
as much blood because it must supply enough blood to
recycle back to the lungs and move out to the body. As
the heart responds to the increased demands for more
oxygenated blood by pumping harder, the pulmonary
artery has to change in size and shape in order to adapt
to the increased amount and force of the blood. In
some cases, the increase in size and shape changes the
pressure in the pulmonary artery and lungs. If the
pressure in the lungs is higher than that of the heart
and body, blood returning to the heart will take the
short cut back into the aorta from the pulmonary
artery through the PDA instead of going to the
lungs. This backward flowing of blood does not
carry much oxygen. If blood without much oxygen is
being delivered to the body, the legs and toes will turn
blue or cyanotic. This is called a shunt reversal.
When a PDA results in a large amount of blood
being cycled in the wrong order, either through a leftto-right shunt or shunt reversal, the overworked,
enlarged heart may stop working (congestive heart
failure) and the lungs can become filled with too
much fluid (pulmonary edema). At this time, there is
also an increased risk for a bacterial infection that can
inflame the lining of the heart (endocarditis). These
three complications are very serious.
PDA is a very common heart defect. Though an
exact incidence of PDA is difficult to determine, one
review in 1990 found that approximately 8% of live
births were found to be affected by PDA. PDA can
occur in full-term infants, but it seen most frequently
in preterm infants, infants born at a high altitude, and
babies whose mothers were affected by the German
measles (rubella) during pregnancy. PDA is two to
three times more common in females than males.
PDA occurs in individuals of every ethnic origin and
does not occur more frequently in any one country or
ethnic population.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
PDA can be a result of an environmental exposure
before birth, inheriting a specific changed or mutated
gene or genes, a symptom of a genetic syndrome, or be
caused by a combination of genetic and environmental
factors (multifactorial).
Environmental exposures that can increase the
chance for a baby to be affected by PDA include
fetal exposure to rubella before birth, preterm delivery, and birth at a high altitude location.
PDA can be an inherited condition running in
families as isolated PDA or part of a genetic syndrome. In either case, there are specific gene changes
or mutations which lead to a defect in the elastic tissue
forming the walls of the ductus arteriosus. The genes
causing isolated PDA have not been identified, but it is
known that PDA can be inherited through a family in
an autosomal dominant pattern or an autosomal
recessive pattern.
Every person has approximately 30,000 genes,
which tell our bodies how to grow and develop correctly. Each gene is present in pairs since one is inherited from our mother, and one is inherited from our
father. In an autosomal dominant condition, only one
specific changed or mutated copy of the gene for PDA
is necessary for a person to have PDA. If a parent has
an autosomal dominant form of PDA, there is a 50%
chance for each child to have the same or similar
condition.
PDA can also be inherited in an autosomal recessive manner. A recessive condition occurs when a child
receives two changed or mutated copies of the gene for
a particular condition, such as PDA (one copy from
each parent). Individuals with a single changed or
mutated copy of a gene for a recessive condition, are
known as ‘‘carriers,’’ and have no health problems
related to the condition. In fact, each of us carries
between five and 10 genes for harmful, recessive
conditions. However, when two people who each
carry a changed or mutated copy of the same gene
for a recessive condition meet, there is a chance, with
each pregnancy, for the child to inherit the two changed or mutated copies from each parent. In this case,
the child would have PDA. For two known carriers,
there is a 25% risk with each child to have a child with
PDA, a 50% chance to have a child who is a carrier,
and a 25% chance to have a child who is neither
affected nor a carrier.
Most cases of PDA occur as the result of multifactorial inheritance which is caused by the combination of genetic factors and environmental factors. The
2811

Patent ductus arteriosus

The pressure between the heart and lungs of an individual affected by PDA causes some of the oxygenated
blood that should go out to the body (through the aorta)
to return back through the PDA into the pulmonary
artery. The pulmonary artery takes the blood immediately back to the lungs. The recycling of the already
oxygenated blood forces the heart to work harder as
it tries to supply enough oxygenated blood to the body.
In this case, usually the left side of the heart grows larger
as it works harder and must contain all of the extra
blood moving back into the heart. This is know as a
left-to-right or aortic-pulmonary shunt.

Patent ductus arteriosus

Normal circulation

Patent ductus arteriosus

Patent ductus arteriosus (PDA) is the failure of the ductus arteriosus to close after birth, allowing blood to inappropriately flow
from the aorta into the pulmonary artery. (Illustration by Electronic Illustrators Group.)

combined factors lead to isolated defects in the elastic
tissue forming the walls of the ductus arteriosus.
Family studies can provide different recurrence
risks depending on the family member affected by
multifactorial PDA. If an individual is affected by
isolated, multifactorial PDA, they have a 2–4%
chance of having a child affected by PDA. If a couple
has one child with isolated, multifactorial PDA, there
is a 3% chance that another of their children could be
affected by PDA. If a couple has two children affected
by isolated, multifactorial PDA, there is a 10–25%
chance that they could have another child affected
by PDA.
Unless a specific pattern of inheritance, preterm
delivery, or known exposure is found through the
examination of a detailed pregnancy and family history, the multifactorial family studies are used to estimated the possible risk of recurrence of PDA in a
family.
The main sign of PDA is a constant heart murmur
that sounds like the hum of a refrigerator or other
machinery. This murmur is usually heard by the doctor using a stethoscope. Otherwise, there are no
2812

specific symptoms of PDA, unless the ductus arteriosus size is large. Children and adults with a large
ductus arteriosus can show difficulty in breathing during moderate physical exercise, an enlarged heart, and
failure to gain weight. In some cases, heart failure and
pulmonary congestion can indicate a PDA.

Diagnosis
Diagnosis is most often made by detecting the
characteristic ‘‘machinery’’ heart murmur heard by a
doctor through a stethoscope. Tests such as a chest x
ray, echocardiograph, and ECG are used to support
the initial diagnosis. Other indications of PDA include
failure to gain weight, frequent chest infections, heavy
breathing during mild physical exertion, congestive
heart failure, and pulmonary edema. Prenatal ultrasounds are unable to detect PDA because the heart
defect does not occur until the time of birth.

Treatment
The treatment and management of PDA depends
upon the size of the PDA and symptoms being
GALE ENCYCLOPEDIA OF MEDICINE

Aorta—The main artery located above the heart
which pumps oxygenated blood out into the body.
Many congenital heart defects affect the aorta.
Catheterization—The process of inserting a hollow
tube into a body cavity or blood vessel.
Ductus arteriosus—The temporary channel or
blood vessel between the aorta and pulmonary
artery in the fetus.
Echocardiograph—A record of the internal structures of the heart obtained from beams of ultrasonic
waves directed through the wall of the chest.
Electrocardiogram (ECG, EKG)—A test used to
measure electrical impulses coming from the heart
in order to gain information about its structure or
function.

and frequently occurs without complications. Proper
treatment allows children and adults to lead normal
lives.
Resources
BOOKS

Jaworski, Anna Marie, editor. The Heart of a Mother.
Temple, Texas: Baby Hearts Press, 1999.
ORGANIZATIONS

CHASER (Congenital Heart Anomalies Support,
Education, and Resources). 2112 North Wilkins Rd.,
Swanton, OH 43558. (419) 825-5575. <http://
www.csun.edu/~hfmth006/chaser>.
Kids with Heart. 1578 Careful Dr., Green Bay, WI 54304.
(800) 538-5390. <http://www.execpc.com/~kdswhrt>.
OTHER

Endocarditis—A dangerous infection of the heart
valves caused by certain bacteria.
Oxygenated blood—Blood carrying oxygen
through the body.

Berger, Sheri. The Congenital Heart Defects Resource Page.
January 6, 2000. <http://www.csun.edu/
~hfmth006/chaser/>.
‘‘Congenital Cardiovascular Disease.’’American Heart
Association 2000. <http://www.americanheart.org/
Heart_and_Stroke_A_Z_Guide/conghd.html>.
‘‘Heart Disorders.’’ Family Village. March 24, 2000.
<http://www.familyvillage.wisc.edu/index.html>.

Pulmonary artery—An artery that carries blood
from the heart to the lungs.

Dawn A. Jacob

Pulmonary edema—A problem caused when fluid
backs up into the veins of the lungs. Increased
pressure in these veins forces fluid out of the vein
and into the air spaces (alveoli). This interferes with
the exchange of oxygen and carbon dioxide in the
alveoli.

experienced by the affected individual. In some cases,
a PDA can correct itself in the first months of life. In
preterm infants experiencing symptoms, the first step
in correcting a PDA is treatment through medications
such as indomethacin. In preterm infants whose PDA
is not closed through medication, full term infants
affected by PDA, and adults, surgery is an option
for closing the ductus arteriosus. In 2000 and 2001,
medicine has developed and reviewed alternatives to
surgical closure such as interventional cardiac catheterization and video-assisted thorascopic surgical
repair. A cardiologist can help individuals determine
the best method for treatment based on their physical
symptoms and medical history.

Prognosis
Adults and children can survive with a small opening remaining in the ductus arteriosus. Treatment,
including surgery, of a larger PDA is usually successful
GALE ENCYCLOPEDIA OF MEDICINE

PCV see Hematocrit
Pediculosis see Lice infestation
Pedophilia see Sexual perversions

Pellagra
Definition
Pellagra is a disorder brought on by a deficiency
of the nutrient called niacin or nicotinic acid, one of
the B-complex vitamins.

Description
Nicotinic acid plays a crucial role in the cellular
process called respiration. Respiration is the process
by which nutrients (specifically sugar, or glucose) and
oxygen are taken in, chemical reactions take place,
energy is produced and stored, and carbon dioxide
and wastes are given off. This process is absolutely
central to basic cell functioning, and thus the functioning of the body as a whole.
Niacin is a B vitamin found in such foods as yeast,
liver, meat, fish, whole-grain cereals and breads, and
2813

Pellagra

KEY TERMS

Pellagra

legumes. Niacin can also be produced within the body
from the essential amino acid called tryptophan.
Dietary requirements for niacin depend on the age,
gender, size, and activity level of the individual.
Niacin requirements range from 5 mg in infants up
to 20 mg in certain adults.

Causes and symptoms
Pellagra can be either primary or secondary.
Primary pellagra results when the diet is extremely
deficient in niacin-rich foods. A classic example occurs
in geographic locations where Indian corn (maize) is
the dietary staple. Maize does contain niacin, but in a
form which cannot be absorbed from the intestine
(except when it has been treated with alkali, as happens in the preparation of tortillas). People who rely
on maize as their major food source often develop
pellagra. Pellagra can also occur when a hospitalized
patient, unable to eat for a very prolonged period of
time, is given fluids devoid of vitamins through a
needle in the vein (intravenous or IV fluids).
Secondary pellagra occurs when adequate quantities of niacin are present in the diet, but other
diseases or conditions interfere with its absorption
and/or processing. This is seen in various diseases
that cause prolonged diarrhea, with cirrhosis of the
liver and alcoholism, with long-term use of the antituberculosis drug called isoniazid, in patients with
malignant carcinoid tumor, and in patients suffering
from Hartnup disease (an inherited disorder which
results in disordered absorption of amino acids from
the intestine and kidney).
Pellagra causes a variety of symptoms affecting
the skin; mucous membranes (moist linings of the
mouth, organs, etc.); central nervous system (including the brain and nerves); and the gastrointestinal
system. The classic collection of symptoms includes
redness and swelling of the mouth and tongue, diarrhea, skin rash, and abnormal mental functioning,
including memory loss. While early patients may
simply have a light skin rash, over time the skin
becomes increasingly thickened, pigmented, and may
slough off in places. Areas of the skin may become
prone to bacterial infection. The mouth and tongue,
and sometimes the vagina, become increasingly thick,
swollen, and red. Abdominal pain and bloating occur,
with nausea and vomiting, and bloody diarrhea to
follow. Initial mental changes appear as inability to
sleep (insomnia), fatigue, and a sense of disconnectedness (apathy). These mental changes progress to memory loss, confusion, depression, and hallucinations (in
which the individual sees sights or hears sounds that
2814

KEY TERMS
Niacinamide—A form of niacin, which is usually
used as a dietary supplement for people with insufficient niacin.
Respiration—Respiration is the process by which
nutrients (specifically sugar, or glucose) and oxygen
are taken in to a cell; chemical reactions take
place; energy is produce and stored; and carbon
dioxide and wastes are given off.

do not really exist). The most severe states include
stiffness of the arms and legs, with resistance to
attempts to move the limbs; variations in level of
consciousness; and the development of involuntary
sucking and grasping motions. This collection of
symptoms is called ‘‘encephalopathic syndrome.’’

Diagnosis
Diagnosis is purely based on the patient’s collection of symptoms, together with information regarding the patient’s diet. When this information points to
niacin deficiency, replacement is started, and the diagnosis is then partly made by evaluating the patient’s
response to increased amounts of niacin. There are no
chemical tests available to definitively diagnose
pellagra.

Treatment
Treatment of pellagra usually involves supplementing the individual’s diet with a form of niacin
called niacinamide (niacin itself in pure supplementation form causes a number of unpleasant side effects,
including sensations of itching, burning, and flushing).
The niacinamide can be given by mouth (orally) or by
injection (when diarrhea would interfere with its
absorption). The usual oral dosage is 300–500 mg
each day; the usual dosage of an injection is 100–250
mg, administered two to three times each day. When
pellagra has progressed to the point of the encephalopathic syndrome, a patient will require 1,000 mg
of niacinamide orally, and 100–250 mg of niacinamide
by injection. Once the symptoms of pellagra have
subsided, a maintenance dose of niacin can be calculated, along with attempting (where possible) to
make appropriate changes in the diet. Because many
B-complex vitamin deficiencies occur simultaneously,
patients will usually require the administration of
other B-complex vitamins as well.
GALE ENCYCLOPEDIA OF MEDICINE

Untreated pellagra will continue progressing over
the course of several years, and is ultimately fatal.
Often, death is due to complications from infections,
massive malnutrition brought on by continuous diarrhea, blood loss due to bleeding from the gastrointestinal tract, or severe encephalopathic syndrome.

should continue once yearly for three years and at
the physicians discretion following this time. Various
groups differ in opinions on when to discontinue
screening for cervical cancer, however, the United
States Preventative Services Task Force recommends
screening continue until age 65 if the patient has not
had previous abnormal results. Women who have
undergone a total hysterectomy for reasons other
than cervical cancer do not need to be screened.

Prevention
Prevention of pellagra is completely possible; what
is required is either a diet adequate in niacin-rich foods,
or appropriate supplementation. However, in many
geographic locations in the world such foods are
unavailable to the general population, and pellagra
becomes an unavoidable complication of poverty.
Resources
ORGANIZATIONS

American Dietetic Association, 216 W. Jackson Blvd.,
Chicago, IL 60606-6995. (800) 745-0775.
<http://www.eatright.org/cdr.html>.

Rosalyn Carson-DeWitt, MD

Pelvic endoscopy see Laparoscopy

Pelvic exam
Definition
A pelvic examination is a routine procedure used
to assess the well being of the female patients’ lower
genito-urinary tract. This is done as part of a usual
health screening and prevention tool, and is an element of the total health care for the female patient.

Purpose
Pelvic exams are useful as a screening tool for
sexually transmitted diseases such as gonorrhea,
chlamydia, genital warts, herpes, and syphilis. In addition, exams detect some forms of cancer that may
affect the genitalia. By analyzing the cervical region
with a Papanicolaou or Pap smear, clinicians are able
to look for signs of cervical cancer. The American
Cancer Society and the American College of
Obstetricians and Gynecologists recommend pelvic
exams with Pap tests for women starting at age 18. It
is also recommended that exams start earlier if the
teenager requests oral contraception. Pap smears
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Pelvic examinations are safe procedures, thus no
precautions are necessary.

Description
The first part of the examination involves visual
inspection and palpation of the external genitalia. The
examiner will note the characteristics of the labia
majora, labia minora, clitoris, urethral orifice, and
the Skene’s and Bartholin’s glands. In addition, the
perineum and anus will be checked. The clinician will
be examining these areas for any indication of swelling, inflammation, abnormal discharge, polyps,
abnormal odor, or other lesions.
The next part involves examining the internal
genitalia. The examiner will first insert a gloved finger
into the vagina in order to palpate the cervix. Next an
instrument called a speculum is inserted. This device is
made of plastic or metal and used to open the vaginal
cavity in order for the examiner to be able to view
the vaginal walls and cervix. Any lesions, bleeding,
or abnormal discharge can be visualized with the
speculum in place. If indicated, a Pap smear will then
be performed. With the speculum still in place, the
examiner gently scrapes the patient’s cervix with a
wooden or plastic spatula as well as a cylindricaltype brush. The spatula collects cells from the outer
surface of the cervix, while the brush is used to collect
cells from the inner-cervix. The collected cells are then
spread on a glass slide, sprayed with a fixative, and
sent to a laboratory for analysis. The examiner may
then insert a cotton or Dacron swab into the cervix.
This will be held in place for 10–30 seconds and when
withdrawn spread on a plastic plate or into a tube
containing a reagent for the specimen. This procedure
may be repeated again with the anus. Such swab
tests are used to check for gonorrhea and chlamydia,
or bacterial vaginitis, which is a bacterial infection
resulting in inflammation of the vagina.
Following the Pap smear is the bimanual examination during which the examiner will place an index
2815

Pelvic exam

Prognosis

Pelvic exam

Bladder
Uterus
Cervix

Speculum
Rectum

During a pelvic exam, cells from the cervix are scraped on a spatula and are tested for abnormalities. (Illustration by Argosy Inc.)

and middle finger into the vagina to first examine the
vaginal walls for any irregularities or tenderness. The
cervix will then be palpated in order to note its shape,
consistency, mobility, and any tenderness. The examiner will then place his or her other hand on the abdomen and gently push down while pushing the cervix
up. This is done to assess the size and shape of the
uterus, and also to note any tenderness or abnormal
lesions. During this time, the ovaries are also checked
for any masses, or tenderness.
The last part of the pelvic exam is the rectovaginal
examination. This allows the clinician to better examine the pelvic organs and structures. The examiner will
place their index finger into the vagina and a lubricated, gloved middle finger against the anus. During
this part, the patient may feel an urgency to have a
bowel movement. However, this is a natural feeling
and a bowel movement will not occur. The patient will
then be asked to strain down in order for the anal
sphincter to relax. As relaxation occurs the examiner
will insert the middle finger into the rectum, enabling
the position and shape of the uterus to be better
assessed. In addition, any masses or tenderness can
be evaluated at this point. The anal canal and rectum
can also be examined for any polyps, or other lesions
at this time. After the rectovaginal exam, the patient
will be allowed clean off any excess lubricant and get
dressed. The examiner will then discuss the procedure
and any findings with the patient.

Preparation
Pelvic exams require the patient to void prior to
starting, as a full bladder can add to discomfort and
2816

make palpation difficult for the examiner. Even
though some tests cannot be done on a menstruating
patient, an examination can still be performed. Any
tampons should be removed prior to the exam.
Douching is not recommended before an exam due
to the hazard of washing away cells that are needed
for examination. If a Pap smear is to be done, the
patients should also refrain from sexual intercourse
or using vaginal suppositories for 24 to 48 hours
prior to the exam. The patient will be asked to undress
and put on a gown. The examiner will instruct the
patient to lie on the examination table on her back
and may assist her in putting her feet in stirrups. The
buttocks are then slid to the edge of the table in order
for a full view of the area to be examined.

Aftercare
Even with the invasiveness of this procedure, the
patient should be able to immediately resume normal
daily activities.

Risks
Other than minor discomfort, there are no risks
associated with a routine pelvic examination.

Normal results
No significant findings by the examiner indicate a
normal pelvic examination. The external and internal
genitalia will be free of any lesions or abnormal discharge. The Pap smear will not reveal cervical dysplasia or abnormal tissue development, and there will not
GALE ENCYCLOPEDIA OF MEDICINE

Bacterial vaginitis—This is the term for inflammation of the vagina due to a bacterial infection.
Bartholin’s glands—These glands are embedded in
the vestibule of the vagina and function to maintain
moisture.
Cervical dysplasia—Dysplasia is the abnormal
growth of the epithelial cells. This is what a Pap
smear will detect in the cervix.
Colposcopy—This procedure is done when a Pap
smear reveals abnormal results. With an endoscope
placed through the vagina and into the cervix, a
physician can determine exactly where lesions of
the cervix are.
Hematoma—Hematomas are masses of blood (or
clotted blood) that accumulate in tissues and may
result from trauma.
Myoma—These are benign (non-malignant) tumors
of the uterus.
Papanicolaou or Pap smear—This is a screening
test for cancer of the cervix. Cells are scraped
from the cervix, smeared on a glass plate, and sent
to a laboratory to examine for any abnormal cells or
dysplasia. This test may also detect other cells seen
in certain vaginal infections.
Skene’s glands—These are the glands of the female
urethra.
Speculum—A speculum is an instrument that is
used during the internal genitalia examination. It
can be made of plastic or metal and is used to open
up the vaginal cavity in order for the examiner to
view the walls of the vagina and the cervix.
Urethral meatus—This is the external opening of
the urethra.

also cause inflammation to the urethral meatus or
the external opening of the urethra. These, in addition
to bacterial infections, can also cause inflammation of
the Skene’s glands, Bartholin’s glands, and vulva.
Infections may result in an irritating discharge.
Discharge may also be noted in yeast infections.
Other abnormal findings of the external genitalia
include carcinomas, vulvar tumors, or hematomas.
Hematomas are masses of accumulated blood that
appears as a bluish swelling of the labium that may
occur following trauma to this area. Examination of
the internal genitalia may reveal similar findings in
regards to sexually transmitted diseases and carcinomas. Cervical abnormalities can also be found and
may include lacerations, infections, ulcers, cysts, and
polyps. All of these will require further evaluation in
order to determine the underlying cause.
Since Pap smears screen for cervical cancer,
abnormal results require special attention. Due to the
incidence of false-positives or false-negatives, the test
may be repeated or the physician may choose to have
the patient undergo a colposcopy. This procedure uses
an endoscope and will examine the vagina and cervix
in more depth. This will identify 100% of lesions present. A biopsy may then be taken of the lesion in order
to determine the exact type of abnormality. Several
new techniques are now available that improve the
accuracy of the Pap smear including automated analysis machines. Bimanual and rectovaginal exams may
reveal abnormalities of the uterus or other pelvic structures. One commonly encountered finding is a
myoma, which is a benign uterine tumor. In addition,
the uterus may be positioned abnormally by being
angled too far forward or backward. Ovarian cysts
and tumors, as well as some disorders of the fallopian
tubes, can be findings of these two exams.
Resources
BOOKS

be any abnormal masses or tenderness upon
palpation.

Abnormal results
The examiner may discover abnormal lesions
during the course of the exam that may require additional tests. Ulcerations, bumps, sores, blisters, or
vesicles on the external genitalia may be signs of a
sexually transmitted disease. Some of the sexually
transmitted diseases that may cause lesions to the
external genitalia include venereal warts, syphilis,
and genital herpes. Gonorrhea or chlamydia may
GALE ENCYCLOPEDIA OF MEDICINE

DeGowin, Richard L., and Donald D. Brown. DeGowin’s
Diagnostic Examination. 7th ed. New York:
McGraw-Hill, 2000.
Johnson, Bruce E., et al. Women’s Health Care Handbook.
2nd ed. Philadelphia: Hanley and Belfus, Inc., 2000.
Seidel, Henry M., et al. Mosby’s Guide to Physical
Examination. 4th ed. St. Louis: Mosby Inc., 1999.
PERIODICALS

Russo, Joseph F. ‘‘Controversies in the Management of
Abnormal Pap Smears.’’ Current Opinion in Obstetrics
and Gynecology 12 (Oct. 2000): 339.
Sawya, George F., et al. ‘‘Current Approaches to CervicalCancer Screening.’’ New England Journal of Medicine
344 (May 2001): 1603.
2817

Pelvic exam

KEY TERMS

Pelvic fracture

Stewart, Felicia H., et al. ‘‘Clinical Breast and Pelvic
Examination Requirements for Hormonal
Contraception: Current Practice vs. Evidence.’’
Journal of the American Medical Association 285
(May 2001): 2232.
OTHER

‘‘Screening for Cervical Cancer.’’ 2001. <http://
my.webmd.com/content/article/1680.50756>.

Laith Farid Gulli, M.D.
Robert Ramirez, B.S.

Pelvic fracture
Definition
A pelvic fracture is a break in one or more bones
of the pelvis.

Description
The pelvis is a butterfly-shaped group of bones
located at the base of the spine. The pelvis consists of
the pubis, ilium, and ischium bones (among others)
held together by tough ligaments. With a cavity in its
center, the pelvis forms one major ring and two smaller
rings of bone that support and protect internal organs
such as the bladder, intestines, and rectum. In women,
the pelvis also surrounds the uterus and vagina. The
pelvis is wider and has a larger cavity in females than in
males because it must accommodate childbirth.
Fractures of the pelvis are uncommon, accounting
for only 0.3–6% of all fractures. Pelvic rings often
break in more than one place. Pelvic fractures range
widely in severity. Disruption of the major ring is
usually a severe injury while disruption of a minor
ring is often not serious. A mild fracture (for example,
one that occurs due to the impact of jogging) may heal
in several weeks without surgery. However, a serious
pelvic fracture can be a life-threatening event requiring
emergency medical care and lengthy rehabilitation.
The latter type of injury may involve damage to
nearby internal organs.
Pelvic fractures are classified as stable or unstable,
and as open or closed. A stable fracture is one in which
the pelvis remains stable and involves one break-point
in the pelvic ring with minimal hemorrhage. An
unstable fracture is one in which the pelvis is unstable
with two or more break-points in the pelvic ring with
moderate to severe hemorrhage. All types of pelvic
2818

fractures are further divided into ‘‘open’’ or ‘‘closed,’’
depending on whether open skin wounds are present or
not in the lower abdomen.

Causes and symptoms
Most pelvic fractures occur during high-speed
accidents (such as car or motorcycle crashes) or falls
from great heights. The greater the force, the greater
the opportunity for a severe fracture. Pelvic fractures
can also occur spontaneously or after minor falls in
people with bone-weakening diseases such as osteoporosis. Less commonly, pelvic fractures may occur
during athletic activities such as football, hockey, skiing, and long-distance running.
The primary symptom of a pelvic fracture is pain
in the groin, hip, or lower back, which may worsen
when walking or moving the legs. Other symptoms
may include abdominal pain; numbness/tingling in
the groin or legs; bleeding from the vagina, urethra
(urine tube), or rectum; difficulty urinating; and difficulty walking or standing. A stress fracture that occurs
while jogging may cause pain in the thigh or buttock.

Diagnosis
A pelvic fracture is typically diagnosed by an
emergency physician looking for bone tenderness, limitations of movement, difficulty walking, and any loss
of nerve function in the lower part of the body. In
addition, the physician looks for signs of injury to
nearby organs of the intestinal or genitourinary systems. This search may include checking the rectum,
vagina, and urethra for signs of bleeding. The physician will order a plain x ray of the pelvis; this will
usually detect the presence of a fracture. Blood and
urine tests may also be done. A computed tomography
(CT) scan will be performed in complicated cases.
Depending on the severity of the fracture, other imaging procedures may be required as well, such as contrasting studies involving the injection of a radioactive
dye; the pictures can be used to evaluate organs and
structures in the pelvic area, such as the urethra, bladder, and blood vessels.

Treatment
In the case of a potentially serious pelvic fracture
(such as that occurring after an accident or high fall),
emergency assistance should be summoned. The person with the injury should be covered with a blanket or
jacket (to maintain body heat), and should not be
moved by non-trained personnel, especially if there is
severe pain or signs of possible nerve injury.
GALE ENCYCLOPEDIA OF MEDICINE

Fracture—A break in a bone.
Computed tomography (CT) scan—An imaging
procedure that produces a series of thin x-ray slices
of internal body organs or structures.
Orthopedist—A doctor who specializes in disorders of the musculoskeletal system.
Osteoporosis—A decrease in the amount of bone
mass, leading to fractures.
Shock—A condition of profound physiological disturbance characterized by failure of the circulatory
system to maintain adequate blood supply to vital
organs.
Stress fracture—A crack in a bone (usually the
result of overuse).

People with bone-weakening conditions such as
osteoporosis or cancer, or tendencies to fall are more
vulnerable to bone fractures. They should follow their
treatment regimens and make use of canes and other
walking aids as well as safety devices in the home
(bars, non skidding mats) and avoid climbing up,
even on a small stool.
Resources
PERIODICALS

Korovessis, P., et al. ‘‘Medium- and long-term results of
open reduction and internal fixation for unstable
pelvic ring fractures.’’Orthopedics November 2000:
1165-71.
Malavaud, B., et al. ‘‘Evaluation of male sexual function
after pelvic trauma by the International Index of
Erectile Function.’’ Urology June 2000: 842-6.
ORGANIZATIONS

Treatment depends on the severity of the injury.
In the case of a minor fracture, treatment may consist
of bed rest and over-the-counter (OTC) or prescription pain killers. Physical therapy, the use of
crutches, and surgery may also be recommended.
Healing can take anywhere from a few weeks to
several months.
Severe injuries to the pelvis (such as those involving more than one break) can be life threatening,
resulting in shock, extensive internal bleeding, and
damage to internal organs. In these situations, the
immediate goal is to control the bleeding and stabilize
the injured person’s condition. Resuscitation procedures may be required as well as large amounts of
intravenous fluids and blood transfusions if internal
bleeding is present. These injuries often require extensive surgery as well as lengthy rehabilitation.

Alternative treatment
To speed up the healing process, some practitioners of alternative medicine recommend magnetic
field therapy, hydrogen peroxide therapy, calcium,
vitamin D, vitamin B complex, and zinc.

Prognosis
The prognosis for minor pelvic fractures is excellent, with most people gaining full mobility in a matter
of weeks or months. Severe pelvic fractures can be
fatal due to internal bleeding or damage to nearby
organs, or result in chronic pain and physical
disabilities.
GALE ENCYCLOPEDIA OF MEDICINE

American Academy of Orthopaedic Surgeons. 6300 North
River Road, Rosemont, IL 60018-4262. (800)
346-AAOS. <http://www.aaos.org>.

Greg Annussek

Pelvic gynecologic sonogram see Pelvic
ultrasound

Pelvic inflammatory disease
Definition
Pelvic inflammatory disease (PID) is a term used
to describe any infection in the lower female reproductive tract that spreads to the upper female reproductive tract. The lower female genital tract consists of the
vagina and the cervix. The upper female genital tract
consists of the body of the uterus, the fallopian or
uterine tubes, and the ovaries.

Description
PID is the most common and the most serious
consequence of infection with sexually transmitted diseases (STD) in women. Over one million cases of PID
are diagnosed annually in the United States, and it is
the most common cause for hospitalization of reproductive-age women. Sexually active women aged
15–25 are at highest risk for developing PID. The
disease can also occur, although less frequently, in
women having monogamous sexual relationships.
2819

Pelvic inflammatory disease

Prevention

KEY TERMS

Pelvic inflammatory disease

The most serious consequences of PID are increased
risk of infertility and ectopic pregnancy.
To understand PID, it is helpful to understand the
basics of inflammation. Inflammation is the body’s
response to disease-causing (pathogenic) microorganisms. The affected body part may swell due to
accumulation of fluid in the tissue or may become
reddened due to an excessive accumulation of blood.
A discharge (pus) may be produced that consists of
white blood cells and dead tissue. Following inflammation, scar tissue may form by the proliferation of
scar-forming cells and is called fibrosis. Adhesions of
fibrous tissue form and cause organs or parts of organs
to stick together.
PID may be used synonymously with the following terms:


salpingitis (Inflammation of the fallopian tubes)



endometritis (Inflammation of the inside lining of
the body of the uterus)



tubo-ovarian abscesses (Abscesses in the tubes and
ovaries)



pelvic peritonitis (Inflammation inside of the abdominal cavity surrounding the female reproductive
organs)

Causes and symptoms
A number of factors affect the risk of developing
PID. They include:


Age. The incidence of PID is very high in younger
women and decreases as a woman ages.



Race. The incidence of PID is 8–10 times higher in
nonwhites than in whites.



Socioeconomic status. The higher incidence of PID
in women of lower socioeconomic status is due in
part to a woman’s lack of education and awareness
of health and disease and her accessibility to medical
care.



Contraception. Induced abortion, use of an IUD,
non-use of barrier contraceptives such as condoms,
and frequent douching are all associated with a
higher risk of developing PID.



Lifestyle. High risk behaviors, such as drug and
alcohol abuse, early age of first intercourse, number
of sexual partners, and smoking all are associated
with a higher risk of developing PID.



Types of sexual practices. Intercourse during menses
and frequent intercourse may offer more opportunities for the admission of pathogenic organisms to
the inside of the uterus.

2820



Disease. Sixty to 75% of cases of PID are associated
with STDs. A prior episode of PID increases the
chances of developing subsequent infections.

The two major causes of STDs are the organisms
Neisseria gonorrhoeae and Chlamydia trachomatis.
The main symptom of N. gonorrheae infection (gonorrhea) is a vaginal discharge of mucus and pus.
Sometimes bacteria from the colon normally in the
vaginal cavity may travel upward to infect the upper
female genital organs, facilitated by the infection with
gonorrhea. Infections with C. trachomatis and other
nongonoccal organisms are more likely to have mild
or no symptoms.
Normally, the cervix produces mucus which acts
as a barrier to prevent disease-causing microorganisms, called pathogens, from entering the uterus and
moving upward to the tubes and ovaries. This barrier
may be breached in two ways. A sexually transmitted
pathogen, usually a single organism, invades the lining
cells, alters them, and gains entry. Another way for
organisms to gain entry happens when trauma or
alteration to the cervix occurs. Childbirth, spontaneous or induced abortion, or use of an intrauterine
contraceptive device (IUD) are all conditions that may
alter or weaken the normal lining cells, making them
susceptible to infection, usually by several organisms.
During menstruation, the cervix widens and may
allow pathogens entry into the uterine cavity.
Recent evidence suggests that bacterial vaginosis
(BV), a bacterial infection of the vagina, may be associated with PID. BV results from the alteration of the
balance of normal organisms in the vagina, by douching, for example. While the balance is altered, conditions are formed that favor the overgrowth of
anaerobic bacteria, which thrive in the absence of
free oxygen. A copious discharge is usually present.
Should some trauma occur in the presence of anaerobic bacteria, such as menses, abortion, intercourse, or
childbirth, these organisms may gain entrance to the
upper genital organs.
The most common symptom of PID is pelvic pain.
However, many women with PID have symptoms so
mild that they may be unaware that an infection exists.
In acute salpingitis, a common form of PID, swelling of the fallopian tubes may cause tenderness on
physical examination. Fever may be present. Abscesses
may develop in the tubes, ovaries, or in the surrounding pelvic cavity. Infectious discharge may leak into
the peritoneal cavity and cause peritonitis, or
abscesses may rupture causing a life-threatening surgical emergency.
GALE ENCYCLOPEDIA OF MEDICINE

Laparoscopic view of pelvic inflammatory disease. (Custom
Medical Stock Photo. Reproduced by permission.)

Chronic salpingitis may follow an acute attack.
Subsequent to inflammation, scarring and resulting
adhesions may result in chronic pain and irregular
menses. Due to blockage of the tubes by scar tissue,
women with chronic salpingitis are at high risk of
having an ectopic pregnancy. The fertilized ovum is
unable to travel down the fallopian tube to the uterus
and implants itself in the tube, on the ovary, or in the
peritoneal cavity. This condition can also be a lifethreatening surgical emergency.
IUD
IUD usage has been strongly associated with the
development of PID. Bacteria may be introduced to
the uterine cavity while the IUD is being inserted or
may travel up the tail of the IUD from the cervix into
the uterus. Uterine tissue in association with the IUD
shows areas of inflammation that may increase its
susceptibility to pathogens.
Susceptibility to STDs
Susceptibility to STDs involves many factors,
some of which are not known. The ability of the
organism to produce disease and the circumstances
that place the organism in the right place at a time
when a trauma or alteration to the lining cells has
occurred are factors. The individual’s own immune
response also helps to determine whether infection
occurs.

Diagnosis
If PID is suspected, the physician will take a complete medical history and perform an internal pelvic
examination. Other diseases that may cause pelvic
pain, such as appendicitis and endometriosis, must be
GALE ENCYCLOPEDIA OF MEDICINE

Specific diagnosis of PID is difficult to make
because the upper pelvic organs are hard to reach for
samplings. The physician may take samples directly
from the cervix to identify the organisms that may be
responsible for infection. Two blood tests may help
to establish the existence of an inflammatory process.
A positive C-reactive protein (CRP) and an elevated
erythrocyte sedimentation rate (ESR) indicate the
presence of inflammation. The physician may take
fluid from the cavity surrounding the ovaries called
the cul de sac; this fluid may be examined directly for
bacteria or may be used for culture. Diagnosis of PID
may also be done using a laparoscope, but laparoscopy
is expensive, and it is an invasive procedure that
carries some risk for the patient.

Treatment
The goals of treatment are to reduce or eliminate
the clinical symptoms and abnormal physical findings,
to get rid of the microorganisms, and to prevent long
term consequences such as infertility and the possibility of ectopic pregnancy. If acute salpingitis is suspected, treatment with antibiotics should begin
immediately. Early intervention is crucial to keep the
fallopian tubes undamaged. The patient is usually
treated with at least two broad spectrum antibiotics
that can kill both N. gonorrhoeae and C. trachomatis
plus other types of bacteria that may have the potential to cause infection. Hospitalization may be
required to ensure compliance. Treatment for chronic
PID may involve hysterectomy, which may be helpful
in some cases.
If a woman is diagnosed with PID, she should see
that her sexual partner is also treated to prevent the
possibility of reinfection.

Alternative treatment
Alternative therapy should be complementary to
antibiotic therapy. For pain relief, an experienced
practitioner may apply castor oil packs, or use acupressure or acupuncture. Some herbs, such as
Echinacea (Echinacea spp.) and calendula (Calendula
officinalis) are believed to have antimicrobial activity
and may be taken to augment the action of prescribed
antibiotics. General tonic herbs, as well as good
nutrition and rest, are important in recovery and
strengthening after an episode of PID. Blue cohosh
2821

Pelvic inflammatory disease

ruled out. If pelvic examination reveals tenderness or
pain in that region, or tenderness on movement of the
cervix, these are good physical signs that PID is
present.

Pelvic relaxation

Prevention

KEY TERMS
Adhesion—The joining or sticking together of parts
of an organ that are not normally joined together.
C-reactive protein (CRP)—A protein present in
blood serum in various abnormal states, like
inflammation.
Ectopic—Located away from normal position;
ectopic pregnancy results in the attachment and
growth of the fertilized egg outside of the uterus, a
life-threatening condition.
Endometriosis—The presence and growth of functioning endometrial tissue in places other than the
uterus; often results in severe pain and infertility.
Erythrocyte sedimentation rate (ESR)—The rate at
which red blood cells settle out in a tube of
unclotted blood, expressed in millimeters per
hour; elevated sedimentation rates indicate the
presence of inflammation.
Fibrosis—The formation of fibrous, or scar, tissue
which may follow inflammation and destruction of
normal tissue.
Hysterectomy—Surgical removal of the uterus.
Laparoscope—A thin flexible tube with a light on
the endthat is used to examine the inside of the
abdomen; the tube is inserted into the abdomen
by way of a small incision just below the navel.

The prevention of PID is a direct result of the
prevention and prompt recognition and treatment of
STDs or of any suspected infection involving the
female genital tract. The main symptom of infection
is an abnormal discharge. To distinguish an abnormal discharge from the mild fluctuations of normal
discharge associated with the menstrual cycle takes
vigilance and self-awareness. Sexually active women
must be able to detect symptoms of lower genital
tract disease. Ideally these women will be able to
have a frank dialogue regarding their sexual history,
risks for PID, and treatment options with their
physicians. Also, these women should have open
discussions with their sexual partners regarding
disclosure of significant symptoms of possible
infection.
Lifestyle changes should be geared to preventing
the transfer of organisms when the body’s delicate
lining cells are unprotected or compromised. Barrier
contraceptives, such as condoms, diaphragms, and
cervical caps should be used. Women in monogamous
relationships should use barrier contraceptives during
menses and take their physician’s advice regarding
intercourse following abortion, childbirth, or biopsy
procedures.
Resources
BOOKS

Landers, D. V., and R. L. Sweet, editors. Pelvic
Inflammatory Disease. New York: Springer, 1997.

(Caulophyllum thalictroides) and false unicorn root
(Chamaelirium luteum) are recommended as tonics
for the general well-being of the female genital tract.

Karen J. Wells

Prognosis
PID can be cured if the initial infection is treated
immediately. If infection is not recognized, as frequently happens, the process of tissue destruction
and scarring that results from inflammation of the
tubes results in irreversible changes in the tube structure that cannot be restored to normal. Subsequent
bouts of PID increase a woman’s risks manyfold.
Thirty to forty percent of cases of female infertility
are due to acute salpingitis.
With modern antibiotic therapy, death from PID
is almost nonexistent. In rare instances, death may
occur from the rupture of tubo-ovarian abscesses
and the resulting infection in the abdominal cavity.
One recent study has linked infertility, a consequence
of PID, with a higher risk of ovarian cancer.
2822

Pelvic relaxation
Definition
Pelvic relaxation is a weakening of the supportive
muscles and ligaments of the pelvic floor. This condition, which affects women and is usually caused by
childbirth, aging, and problems with support, causes
the pelvic floor to sag and press into the wall of the
vagina.

Description
The pelvic floor normally holds the uterus and
the bladder in position above the vagina. When
the pelvic floor becomes stretched and damaged,
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Childbirth increases the risk of pelvic relaxation.
Other causes include constipation, a chronic cough,
obesity, and heavy lifting. Some women develop the
condition after menopause, when the body loses
the estrogen that helps maintain muscle tone. Mild
pelvic relaxation may cause no symptoms. More
severe pelvic relaxation can cause the following
symptoms:


an aching sensation in the vagina, lower abdomen,
groin or lower back



heaviness or pressure in the vaginal area, as if something is about to ‘‘fall out’’ of the vagina



bladder control problems that worsen with heavy
lifting, coughing, or sneezing



frequent urinary tract infections



difficulty having a bowel movement

Diagnosis
A thorough pelvic exam can help diagnose pelvic
relaxation, as can tests of bladder function.

KEY TERMS
Cystocele—Bulging of the bladder into the vagina.
Cystourethrocele—Bulging of the bladder neck
into the vagina.
Enterocele—Bulging of the intestine into the upper
part of the vagina.
Kegel exercises—Pelvic muscle exercises that
strengthen bladder and bowel control.
Pessary—A device inserted into the vagina to support sagging organs.
Rectocele—Bulging of the rectum into the vaginal
wall.
Uterine prolapse—Bulging of the uterus into the
vagina.
Vaginal prolapse—Bulging of the top of the vagina
into the lower vagina or outside the opening of the
vagina.

Prognosis
Mild cases of pelvic relaxation can sometimes be
reversed through Kegel exercises, while severe cases
usually do not respond to exercise or estrogen therapy,
but usually require pessary support or surgery.

Prevention
To limit stress on the pelvic support system,
women are advised to maintain a normal body weight,
limit heavy lifting, and avoid unnecessary straining to
have bowel movements.

Treatment
Exercises called Kegel exercises can strengthen
pelvic floor muscles and lessen the symptoms of pelvic
relaxation. These exercises involve squeezing the muscles that stop the flow of urine. The pelvic floor can
also be strengthened by estrogen supplements.
Physicians sometimes prescribe the insertion of a supportive ring-shaped device called a pessary into the
vagina, to prevent the uterus and bladder from pressing into the vagina. Sometimes surgery is recommended to repair a sagging bladder or uterus, and
sometimes surgical removal of the uterus (hysterectomy) is recommended. Patients are often advised to
adhere to a high-fiber diet to reduce the strain of bowel
movements, maintain a moderate weight, and avoid
activities that strain the pelvic floor. They are sometimes prescribed medications to help control urination
and prevent leakage.
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th St., S.W., P.O. Box 96920, Washington, DC
20090-6920. <http://www.acog.org>.
American Foundation for Urologic Disease. 1128 North
Charles Street, Baltimore, MD 21201. (800) 242-2383.
<http://www.afud.org>.
National Association For Continence. P.O. Box 8310,
Spartanburg, SC 29305-8310. (800) BLADDER.
<http://www.nafc.org>.
National Kidney and Urologic Diseases Information
Clearinghouse. 3 Information Way, Bethesda, MD,
20892. NIH Publication No. 97-4195. (800) 891-5390.
<http://www.niddk.nih.gov/health/
kidney/nkudic.htm>.

Ann Quigley
2823

Pelvic relaxation

these organs can sag into the vagina, sometimes
bulging out through the vaginal opening. A sagging
uterus is referred to as a uterine prolapse, pelvic
floor hernia, or pudendal hernia. A sagging bladder
is referred to as a bladder prolapse, or cystocele.
Other organs, such as the rectum and intestine, can
also sag into the vagina as a result of a weakened
pelvic floor.

Pelvic ultrasound

Pelvic ultrasound
Definition
Pelvic ultrasound is a procedure where harmless,
high-frequency sound waves are projected into the
abdomen. These waves reflect off of the internal structures and create shadowy black and white pictures on
a display screen.

Purpose
Ultrasound is performed routinely during pregnancy. Early in the pregnancy (at about seven weeks),
it might be used to determine the size of the uterus
or the fetus, to detect multiple or ectopic pregnancy,
to confirm that the fetus is alive (or viable), or to
confirm the due date. Toward the middle of the
pregnancy (at about 16–20 weeks), ultrasound may
be used to confirm fetal growth, to reveal defects in
the anatomy of the fetus, and to check the placenta.
Toward the end of pregnancy, it may be used to
evaluate fetal size, position, growth, or to check the
placenta. Doctors may use ultrasound during diagnostic procedures like amniocentesis and chorionic
villus sampling. Both of these tests use long needles
inserted through the mother’s abdomen into the
uterus or placenta to gather cells. Ultrasound can
also be used in men or women to examine other
internal organs, such as the liver, gallbladder, kidney,
and heart. The procedure can be useful in detecting
cysts, tumors, and cancer of the uterus, ovaries, and
breasts.

the abdomen. The waves are reflected back to the
transducer and the wave patterns are shown as an
image on a display screen. An ultrasound scan reveals
the shapes, densities, and even movements of
organs and tissues. Although the pictures transmitted
by an ultrasound scan appear gray and grainy, a
trained technician can identify the fetus within
the uterus, monitor its heartbeat, and sometimes
determine its sex. Using computerized tools, the
technician can measure various structures shown
on the screen. For example, the length of the upper thigh bone (femur) or the distance between
the two sides of the skull can indicate the age of the
fetus.
Ultrasound technology has been used safely in
medical settings for over 30 years, and several significant improvements have been made to the procedure. A specially designed transducer probe can be
placed in the vagina to provide better ultrasound
images. This transvaginal or endovaginal scan is particularly useful in early pregnancy or in cases where
ectopic pregnancy is suspected. Doppler ultrasound
uses enhanced sound waves to monitor subtle events,
like the flow of fetal blood through the heart and
arteries. Color imaging is a recent addition to ultrasound technology. With this process, color can be
assigned to the various shades of gray for better
visualization of subtle tissue details. A new technology under development is three-dimensional ultrasound, which has the potential for detecting even
very subtle fetal defects.

Preparation
Precautions
There are no special precautions recommended
before an ultrasound examination. Unlike x rays,
ultrasound does not produce any harmful radiation
and does not pose a risk to the mother or the fetus.
While many woman have an ultrasound as part of
their prenatal care, there may be no medical need to
perform the procedure.

Before undergoing a pelvic ultrasound, a woman
may be asked to drink several glasses of water and to
avoid urinating for about one hour before the examination. When the bladder is full, the uterus and fetus
are easier to see. A lubricating gel or mineral oil may
be applied to the area to make moving the transducer
easier.

Aftercare
Description
Ultrasound examinations can be done in a doctor’s office, clinic, or hospital setting. Typically, the
pregnant woman will lie on an examination table
with her abdomen exposed. Gel or oil is applied to
the area. The doctor or technician will move a handheld scanner (called a transducer) over the abdomen.
The transducer emits high-frequency sound waves
(usually in the range of 3.5–7.0 megahertz) into
2824

The lubricating jelly or oil applied to the abdomen
is wiped off at the end of the procedure. After an
ultrasound examination, a patient can immediately
resume normal activities.

Risks
There are no known risks, to either the mother or
the fetus, associated with the use of ultrasound.
GALE ENCYCLOPEDIA OF MEDICINE

Pelvic ultrasound

An ultrasound image of Anabelle Ashlyn Longe at 20 weeks. (Courtesy of Jacqueline Longe.)

Normal results

KEY TERMS
Amniocentesis—A procedure where a needle is
inserted through the pregnant mother’s abdomen
and into the uterus to draw off some of the amniotic
fluid surrounding the fetus.
Chorionic villus sampling—A procedure where a
needle is inserted into the placenta to draw off some
of the placenta’s inner wall cells surrounding the fetus.
Ectopic pregnancy—A pregnancy where the fertilized egg becomes implanted somewhere other
than in the uterus. A tubal pregnancy is when the
fertilized egg implants in the fallopian tube.
Fetus—A term for an unborn baby, usually from the
end of week eight to the moment of birth.
Placenta—The organ that allows interchange
between the fetus and the mother. Blood from the
fetus and the mother do not directly mix, but the
thin placental membrane allows the fetus to absorb
nutrients and oxygen from the mother. Waste products from the fetus can exit through the placenta.
Ultrasonography—Another term for ultrasound.

GALE ENCYCLOPEDIA OF MEDICINE

The reliability of ultrasound readings depends
on the skill of the technician or doctor performing
the scan. Patients should be aware that fetal abnormalities cannot be detected with 100% accuracy
using ultrasound. A normal ultrasound result does
not necessarily guarantee that the fetus will be
normal.

Abnormal results
Ultrasound examinations in obstetrics may
detect abnormalities or defects in the fetus. This
information may reveal that the fetus cannot survive
on its own after birth or that it will require extensive
treatment or care. Some surgical procedures can be
performed to correct defects while the fetus is still in
the uterus. Parents faced with information regarding
possible birth defects may require counseling to
consider their choice to either continue or end the
pregnancy.
The diagnostic use of ultrasound may reveal the
presence of cysts, tumors, or cancer in internal
organs.
2825

Penicillins

Resources
ORGANIZATIONS

American Institute of Ultrasound in Medicine. 14750
Sweitzer Lane, Suite 100, Laurel, MD 20707-5906.
(800) 638-5352. <http://www.aium.org>.

Altha Roberts Edgren

Penicillin V see Penicillins

Penicillins
Definition
Penicillins are medicines that kill bacteria or prevent their growth.

Purpose
Penicillins are antibiotics (medicines used to treat
infections caused by microorganisms). There are several types of penicillins, each used to treat different
kinds of infections, such as skin infections, dental
infections, ear infections, respiratory tract infections,
urinary tract infections, gonorrhea, and other infections caused by bacteria. These drugs will not work
for colds, flu, and other infections caused by viruses.

Description
Examples of penicillins are penicillin V (BeepenVK, Pen-Vee K, V-cillin K, Veetids) and amoxicillin
(Amoxil, Polymox, Trimox, Wymox). Penicillins are
sometimes combined with other ingredients called
beta-lactamase inhibitors, which protect the penicillin
from bacterial enzymes that may destroy it before it
can do its work. The drug Augmentin, for example,
contains a combination of amoxicillin and a betalactamase inhibitor, clavulanic acid.
Penicillins are available only with a physician’s
prescription. They are sold in capsule, tablet (regular
and chewable), liquid, and injectable forms.

Recommended dosage
The recommended dosage depends on the type of
penicillin, the strength of the medicine, and the medical problem for which it is being taken. Check with the
physician who prescribed the drug or the pharmacist
who filled the prescription for the correct dosage.
2826

Always take penicillins exactly as directed. Never
take larger, smaller, more frequent, or less frequent
doses. To make sure the infection clears up completely, take the medicine for as long as it has been prescribed. Do not stop taking the drug just because
symptoms begin to improve. This is important with
all types of infections, but it is especially important
with ‘‘strep’’ infections, which can lead to serious heart
problems if they are not cleared up completely.
Take this medicine only for the infection for which
it was prescribed. Different kinds of penicillins cannot
be substituted for one another. Do not save some of
the medicine to use on future infections. It may not be
the right treatment for other kinds of infections, even
if the symptoms are the same.
Penicillins work best when they are at constant
levels in the blood. To help keep levels constant, take
the medicine in doses spaced evenly through the day
and night. Do not miss any doses.
Some penicillins, notably penicillin V, should be
taken on an empty stomach, but others may be taken
with food. Check package directions or ask the physician or pharmacist for instructions on how to take the
medicine.

Precautions
Symptoms should begin to improve within a few
days of beginning to take this medicine. If they do not,
or if they get worse, check with the physician who
prescribed the medicine.
Penicillins may cause diarrhea. Certain diarrhea
medicines may make the problem worse. Check with a
physician before using any diarrhea medicine to treat
diarrhea caused by taking penicillin. If diarrhea is
severe, check with a physician as soon as possible.
This could be a sign of a serious side effect.
Penicillins may change the results of some medical
tests. Before having medical tests, patients who are
taking penicillin should be sure to let the physician in
charge know that they are taking this medicine.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if they
take penicillins. Before taking these drugs, be sure to let
the physician know about any of these conditions:
ALLERGIES. People who have hay fever, asthma,
eczema, or other general allergies (or who have had
such allergies in the past) may be more likely to have
severe reactions to penicillins. They should be sure
their health care provider knows about their allergies.

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Enzyme—A type of protein that brings about or
speeds up chemical reactions.
Microorganism—An organism that is too small to
be seen with the naked eye.

LOW-SODIUM DIET. Some penicillin medicines
contain large enough amounts of sodium to cause
problems for people on low-sodium diets. Anyone on
such a diet should make sure that the physician treating the infection knows about the special diet.
DIABETES. Penicillins may cause false positive
results on urine sugar tests for diabetes. People with
diabetes should check with their physicians to see if
they need to change their diet or the doses of their
diabetes medicine.
PHENYLKETONURIA. Some

formulations
of
Augmentin contain phenylalanine. People with phenylketonuria (PKU) should consult a physician before
taking this medicine.
OTHER MEDICAL CONDITIONS. Before using penicillins, people with any of these medical problems
should make sure their physicians are aware of their
conditions:


bleeding problems



congestive heart failure



cystic fibrosis



kidney disease



mononucleosis (‘‘mono’’)



stomach or intestinal problems, especially ulcerative
colitis

USE OF CERTAIN MEDICINES. Taking penicillins
with certain other drugs may affect the way the drugs
work or may increase the chance of side effects.

Mononucleosis—An infectious disease with symptoms that include severe fatigue, fever, sore throat,
and swollen lymph nodes in the neck and armpits.
Also called ‘‘mono.’’



joint pain



skin rash, hives, itching, or red, scaly skin



swelling or puffiness in the face

Other rare side effects may occur. Anyone who
has unusual symptoms after taking penicillin should
get in touch with his or her physician.

Interactions
Birth control pills may not work properly when
taken at the same time as penicillin. To prevent pregnancy, use additional methods of birth control while
taking penicillin, such as latex condoms or
spermicide.
Penicillins may interact with many other medicines. When this happens, the effects of one or both
of the drugs may change or the risk of side effects
may be greater. Anyone who takes penicillin should
let the physician know all other medicines he or she
is taking. Among the drugs that may interact with
penicillins are:


Acetaminophen (Tylenol) and other medicines that
relieve pain and inflammation



medicine for overactive thyroid



male hormones (androgens)



female hormones (estrogens)



other antibiotics



blood thinners



Disulfiram (Antabuse), used to treat alcohol abuse



antiseizure medicines such as Depakote and
Depakene



blood pressure drugs such as Capoten, Monopril,
and Lotensin

Side effects
The most common side effects are mild diarrhea,
headache, vaginal itching and discharge, sore mouth
or tongue, or white patches in the mouth or on the
tongue. These problems usually go away as the body
adjusts to the drug and do not require medical treatment unless they continue or they are bothersome.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
get emergency medical help immediately:


breathing problems, such as shortness of breath or
fast or irregular breathing



fever



sudden lightheadedness or faintness

GALE ENCYCLOPEDIA OF MEDICINE

The list above does not include every drug that
may interact with penicillins. Be sure to check with a
2827

Penicillins

Anyone who has had unusual reactions to penicillins or cephalosporins in the past should let his or her
physician know before taking the drugs again. The
physician should also be told about any allergies to
foods, dyes, preservatives, or other substances.

Penile cancer

physician or pharmacist before combining penicillins
with any other prescription or nonprescription (overthe-counter) medicine.
Nancy Ross-Flanigan

Penile cancer
Definition
Penile cancer is the growth of malignant cells on
the external skin and in the tissues of the penis.

Description
Penile cancer is a disease in which cancerous
cells appear on the penis. If left untreated, this
cancer can grow and spread from the penis to the
lymph nodes in the groin and eventually to other
parts of the body.

Demographics
Penile cancer is a rare form of cancer that develops
in about one out of 100,000 men per year in the United
States. Penile cancer is more common in other parts
of the world, particularly Africa and Asia. In Uganda,
penile cancer is the most common form of cancer
for men.

Causes and symptoms
The cause of penile cancer is unknown. The most
common symptoms of penile cancer are:


a tender spot, an open sore, or a wart-like lump on
the penis



unusual liquid discharges from the penis



pain or bleeding in the genital area

Diagnosis
In order to diagnose penile cancer, the doctor
examines the patient’s penis for lumps or other
abnormalities. A tissue sample, or biopsy, may be
ordered to distinguish cancerous cells from syphilis
and penile warts. If the results confirm a diagnosis of
cancer, additional tests are done to determine whether
the disease has spread to other parts of the body.
2828

Treatment
In Stage I penile cancer, malignant cells are found
only on the surface of the head (glans) and on the
foreskin of the penis. If the cancer is limited to the
foreskin, treatment may involve wide local excision
and circumcision. Wide local excision is a form of
surgery that removes only cancer cells and a small
amount of normal tissue adjacent to them.
Circumcision is removal of the foreskin.
If the Stage I cancer is only on the glans, treatment
may involve the use of a fluorouracil cream (Adrucil,
Efudex), and/or microsurgery. Microsurgery removes
cancerous tissue and the smallest possible amount of
normal tissue. During microsurgery, the doctor uses a
special instrument that provides a comprehensive view
of the area where cancer cells are located and makes it
possible to determine that all malignant cells have
been removed.
In Stage II, the penile cancer has spread to the
surface of the glans, tissues beneath the surface, and
the shaft of the penis. The treatment recommended
may be amputation of all or part of the penis (total or
partial penectomy). If the disease is diagnosed
early enough, surgeons are often able to preserve
enough of the organ for urination and sexual activity.
Treatment may also include microsurgery and
external radiation therapy, in which a machine
provides radiation to the affected area. Laser surgery is an experimental treatment for Stage II
cancers. Laser surgery uses an intense precisely
focused beam of light to dissolve or burn away cancer
cells.
In Stage III, malignant cells have spread to
lymph nodes in the groin, where they cause swelling.
The recommended treatment may include amputation of the penis and removal of the lymph nodes on
both sides. Radiation therapy may also be suggested.
More advanced disease requires systemic treatments
using drugs (chemotherapy). In chemotherapy,
medicines are administered intravenously or taken
by mouth. These drugs enter the bloodstream
and kill cancer cells that have spread to any part of
the body.
In Stage IV, the disease has spread throughout the
penis and lymph nodes in the groin, or has traveled to
other parts of the body. Treatments are similar to that
for Stage III cancer.
Recurrent penile cancer is disease that recurs
in the penis or develops in another part of the
body after treatment has eradicated the original
cancer cells.
GALE ENCYCLOPEDIA OF MEDICINE

Circumcision—Surgical removal of the foreskin
of the penis. It is usually performed shortly after
birth.
Fluorouracil—A cell-killing (cytotoxic) medication
that can be applied in cream form to treat cancer of
the penis.

Cure rates are high for cancers diagnosed in
Stage I or II, but much lower for Stages III and IV,
by which time cancer cells have spread to the lymph
nodes.

Alternative treatment
In addition to the treatments previously
described, biological therapy is another treatment
that is currently being studied. Biological therapy is a
type of treatment that is sometimes called biological
response modifier (BRM) therapy. It uses natural or
artificial substances to boost, focus, or reinforce the
body’s disease-fighting resources.

Prevention
Conditions which increase a person’s chance of
getting penile cancer include:


infection with genital warts (human papillomavirus,
or HPV)



a skin disease called psoriasis



a condition called phimosis, in which the foreskin
becomes difficult to retract



other conditions that result in repeated irritation of
the penis.



a history of smoking.

There appears to be a connection between development of the disease and lack of personal hygiene.
Failure to regularly and thoroughly cleanse the part of
the penis covered by the foreskin increases the risk of
developing the disease. Penile cancer is also more
common in uncircumcised men.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800) ACS-2345.
<http://www.cancer.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Cancer Group Institute. 17620 9th Ave. NE,
North Miami Beach, FL 33162.
(305) 493-1980. <http://
www.cancergroup.com>.
OTHER

CancerNet: Penile Cancer. March 25, 2001. [cited June 28,
2001]. <http://www.cancernet.nci.nih.gov/
cancer_types/penile_cancer.shtml>.

Maureen Haggerty
Paul A. Johnson, Ed.M.

Penile implant surgery see Penile prostheses

Penile prostheses
Definition
Penile prostheses are semirigid or inflatable
devices that are implanted into penises to alleviate
impotence.

Purpose
The penis is composed of one channel for urine
and semen and three compartments with tough,
fibrous walls containing ‘‘erectile tissue.’’ With appropriate stimulation, the blood vessels that lead out
of these compartments constrict, trapping blood.
Blood pressure fills and hardens the compartments
producing an erection of sufficient firmness to perform sexual intercourse. Additional stimulation leads
to ejaculation, where semen is pumped out of the
urethra. When this system fails, impotence (failure to
create and maintain an erection) occurs.
Impotence can be caused by a number of conditions, including diabetes, spinal cord injury, prolonged
drug abuse, and removal of a prostate gland. If the
medical condition is irreversible, a penile prosthesis
may be considered. Patients whose impotence is
caused by psychological problems are not recommended for implant surgery.

Description
Penile implant surgery is conducted on patients
who have exhausted all other areas of treatment. The
semirigid device consists of two rods that are easier
and less expensive to implant than the inflatable cylinders. Once implanted, the semirigid device needs no
follow-up adjustments, however it produces a penis
which constantly remains semi-erect. The inflatable
2829

Penile prostheses

KEY TERMS

Penile prostheses

Fluid-filled reservoir

Inflatable cylinders

Penis

Pump

The inflatable implant is a common penile prosthesis. This device connects through a tube to a flexible fluid reservoir and a
pump. The pump is shaped like a testicle and inserted in the scrotum. When the pump is squeezed, the fluid is forced into the
inflatable cylinders implanted inside the penis, producing an erection. (Illustration by Electronic Illustrators Group.)

cylinders produce a more natural effect. The patient is
able to simulate an erection by using a pump located in
the scrotum.
With the patient asleep under general anesthesia,
the device is inserted into the erectile tissue of the penis
through an incision in the fibrous wall. In order to
implant the pump for the inflatable implant, incisions
are made in the abdomen and the perineum (area
between the anus and the genitals). A fluid reservoir
is inserted into the groin and the pump is placed in
the scrotum. The cylinders, reservoir, and pump are
connected by tubes and tested before the incisions are
closed.
2830

Preparation
Surgery always requires an adequately informed
patient, both as to risks and benefits. In this case, the
sexual partner should also be involved in the discussion. Prior to surgery, antibacterial cleansing occurs
and the surrounding areas are shaved.

Aftercare
To minimize swelling, ice packs are applied to the
penis for the first 24 hours following surgery. The
incision sites are cleansed daily to prevent infection.
Pain relievers may be taken.
GALE ENCYCLOPEDIA OF MEDICINE

General anesthesia—Deep sleep induced by a
combination of medicines that allows surgery to
be performed.
Genital—Sexual organ.
Perineum—Area between the anus and genitals.
Scrotum—The external pouch containing the male
reproductive glands (testes) and part of the spermatic cord.

Risks
With any implant, there is a slightly greater risk of
infection. The implant may irritate the penis and cause
continuous pain. The inflatable prosthesis may need
follow-up surgery to repair leaks in the reservoir or to
reconnect the tubing.
Resources

system. If the dye does not distribute evenly, this is
indicative of a blockage, which may be caused by a
gallstone or a tumor in the liver, bile ducts, or
pancreas.

Precautions
Patients should report allergic reactions to:


anesthetics



dyes used in medical tests



iodine



shellfish

PTHC should not be performed on anyone who
has cholangitis (inflammation of the bile duct), massive ascites, a severe allergy to iodine, or a serious
uncorrectable or uncontrollable bleeding disorder.
Patients who have diabetes should inform their
doctor.

Description

BOOKS

Jordan, Gerald H., et al. ‘‘Surgery of the Penis and
Urethra.’’ In Campbell’s Urology, edited by Patrick C.
Walsh, et al. Philadelphia: W. B. Saunders Co., 1998.

J. Ricker Polsdorfer, MD

Pentoxifylline see Blood-viscosity reducing
drugs
Peptic ulcer disease see Heliobacteriosis
Percutaneous renal biopsy see Kidney biopsy

Percutaneous transhepatic
cholangiography
Definition
Percutaneous transhepatic cholangiography
(PTHC) is an x-ray test used to identify obstructions
either in the liver or bile ducts that slow or stop the
flow of bile from the liver to the digestive system.

Purpose
Because the liver and bile ducts are not normally
seen on x rays, the doctor injects the liver with a special
dye that will show up on the resulting picture. This dye
distributes evenly to fill the whole liver drainage
GALE ENCYCLOPEDIA OF MEDICINE

PTHC is performed in a hospital, doctor’s office,
or outpatient surgical or x-ray facility. The patient lies
on a movable x-ray table and is given a local anesthetic. The patient will be told to hold his or her
breath, and a doctor, nurse, or laboratory technician
will inject a special dye into the liver as the patient
exhales.
The patient may feel a twinge when the needle
penetrates the liver, a pressure or fullness, or brief
discomfort in the upper right side of the back. Hands
and feet may become numb during the 30–60 minute
procedure.
The x-ray table will be rotated several times during the test, and the patient helped to assume a variety
of positions. A special x-ray machine called a fluoroscope will track the dye’s movement through the bile
ducts and show whether the fluid is moving freely or if
its passage is obstructed.
PTHC costs about $1,600. The test may have to be
repeated if the patient moves while x rays are being
taken.

Preparation
An intravenous antibiotic may be given every 4–6
hours during the 24 hours before the test. The patient
will be told to fast overnight. Having an empty stomach is a safety measure in case of complications, such
as bleeding, that might require emergency repair surgery. Medications such as aspirin, or non-steroidal
2831

Percutaneous transhepatic cholangiography

KEY TERMS

Perforated eardrum

KEY TERMS
Ascites—Abnormal accumulation of fluid in the
abdomen.
Bile ducts—Tubes that carry bile, a thick yellowishgreen fluid that is made by the liver, stored in the
gallbladder, and helps the body digest fats.

occasionally leaks from the liver into the abdomen,
and there is a slight risk of bleeding or infection.

Normal results
Normal x rays show dye evenly distributed
throughout the bile ducts. Obesity, gas, and failure to
fast can affect test results.

Cholangitis—Inflammation of the bile duct.
Fluoroscope—An x-ray machine that projects
images of organs.
Granulomatous disease—Characterized by growth
of tiny blood vessels and connective tissue.
Jaundice—Disease that causes bile to accumulate
in the blood, causing the skin and whites of the eyes
to turn yellow. Obstructive jaundice is caused by
blockage of bile ducts, while non-obstructive jaundice is caused by disease or infection of the liver.

anti-inflammatory drugs that thin the blood, should be
stopped three–seven days prior to taking the PRHC
test. Patients may also be given a sedative a few minutes before the test begins.

Aftercare
A nurse will monitor the patient’s vital signs and
watch for:


itching



flushing



nausea and vomiting



sweating



excessive flow of saliva



possible serious allergic reactions to contrast dye

The patient should stay in bed for at least six
hours after the test, lying on the right side to prevent
bleeding from the injection site. The patient may
resume normal eating habits and gradually resume
normal activities. The doctor should be informed
right away if pain develops in the right abdomen or
shoulder or in case of fever, dizziness, or a change in
stool color to black or red.

Abnormal results
Enlargement of bile ducts may indicate:


obstructive or non-obstructive jaundice



cholelithiasis (gallstones)



hepatitis (inflammation of the liver)



cirrhosis (chronic liver disease)



granulomatous disease



pancreatic cancer



bile duct or gallbladder cancers

Resources
BOOKS

Komaroff, A. L. The Harvard Medical School Family Health
Guide. New York: Simon & Schuster, 1999.
PERIODICALS

Cieszanowski, A., et al. ‘‘Imaging Techniques in Patients
with Biliary Obstruction.’’ Medical Science Monitor 6
(November-December 2000): 1197-202.
OTHER

Percutaneous Transhepatic Cholangiography. <http://
207.25.144.143/health/Library/medtests/>.
Percutaneous Transhepatic Cholangiography (PTHC).
<http://www.uhs.org/frames/health/test/
test3554.htm>.
Test Universe Site: Percutaneous Transhepatic
Cholangiography. <http://www.testuniverse.com/
mdx/MDX-3055.html>.

Maureen Haggerty

Perforated eardrum
Definition

Risks
Septicemia (blood poisoning) and bile peritonitis
(a potentially fatal infection or inflammation of the
membrane covering the walls of the abdomen) are rare
but serious complications of this procedure. Dye
2832

A perforated eardrum exists when there is a hole
or rupture in the eardrum, the thin membrane that
separates the outer ear canal from the middle ear. A
perforated eardrum may cause temporary hearing loss
and occasional discharge.
GALE ENCYCLOPEDIA OF MEDICINE

The eardrum (tympanic membrane) is a thin wall
that separates the outer ear from the middle ear,
vibrating when sound waves strike the membrane.
The middle ear is connected to the nose by the
Eustachian tube.
In addition to conducting sound, the eardrum also
protects the middle ear from bacteria. When it is perforated, bacteria can more easily get into this part of
the ear, causing ear infections.
In general, the larger the hole in the eardrum, the
greater the temporary loss of hearing. The location of
the perforation also affects the degree of hearing loss.
Severe hearing loss may follow a skull fracture that
disrupts the bones in the middle ear. Eardrum perforation caused by a loud noise may result in ringing in the
ear (tinnitus), in addition to a temporary hearing loss.
Over time, this hearing loss improves and the ringing
usually fades in a few days.

Causes and symptoms
The eardrum can become damaged by a direct
injury. It is possible to perforate the eardrum:


with a cotton-tipped swab or another foreign object



by hitting the ear with an open hand



after a skull fracture



after a loud explosion or other loud noise

In addition, an ear infection can rupture the eardrum as pressure within the middle ear rises when fluid
builds up. If the eardrum is punctured by pressure
from an ear infection, there may be infected or bloody
drainage from the ear.
Rarely, a small hole may remain in the eardrum
after a pressure-equalizing tube falls out or is removed
by a doctor.
Symptoms include an earache or pain in the ear,
which may be severe, or a sudden decrease in ear pain,
followed by ear drainage of clear, bloody, or pus-filled
fluid, hearing loss, or ear noise/buzzing.

Diagnosis
A doctor can diagnose a perforated eardrum by
direct inspection with an otoscope. Hearing tests may
reveal a hearing loss.

Treatment
A perforated eardrum usually heals by itself
within two months. Antibiotics may be given to
GALE ENCYCLOPEDIA OF MEDICINE

Perforated eardrum

Description

Anvil (incus)
Stirrup (stapes)

Hammer (malleus)
Rupture

Eardrum

A perforated eardrum is caused by a hole or rupture in the
eardrum, the thin membrane that separates the outer ear
canal from the middle ear. It may result in temporary hearing
loss and occasional discharge. (Illustration by Electronic
Illustrators Group.)

KEY TERMS
Eustachian tube—The air duct that connects the
area behind the nose to the middle ear.
Otoscope—An instrument used to examine the ear,
to inspect the outer ear canal and the eardrum, and
to detect diseases in the middle ear.

prevent infection or to treat an existing ear infection.
Painkillers can relieve any ear pain.
Sometimes, a paper patch is placed over the
eardrum until the membrane heals. Three or four
patches may be needed before the perforation
closes completely. If the eardrum does not heal on
its own, surgical repair (tympanoplasty) may be
necessary.
The ear should be kept clean and dry while the
eardrum heals; patients should insert cotton balls into
the ear when showering or shampooing to block any
water from getting into the ear. Pain in the ear may be
eased by applying warm compresses.
2833

Perforated septum

Prognosis

KEY TERMS

While a perforated eardrum may be uncomfortable, it usually heals on its own. Any hearing loss that
accompanies the perforation is usually temporary.

Systemic lupus erythematosus—A collagen-vascular
disease in the autoimmune category that causes
damage to many different parts of the body.

Prevention
A perforated eardrum can be prevented by avoiding insertion of any object into the ear to clean it. If a
foreign object becomes lodged in the ear, only a doctor
should try to remove it.

close. It is used in nose surgery because it shrinks
mucus membranes, permitting better visualization
and access into the nose. Used continuously, tissues
are deprived of blood and die. The nasal septum is
the most vulnerable to this effect of sniffing cocaine.

Promptly treating all ear infections is another way
to guard against a ruptured eardrum.
Resources



Getting the septum cauterized. Nosebleeds usually
come from the front part of the nasal septum, which
is rich in blood vessels. Uncontrolled repeated bleeding from these vessels may require cautery–burning
the vessels with electricity or chemicals to close them
off. Injudicious cautery of both sides of the septum
has in the past led to death of tissue and consequent
perforation.



More and more people are having cosmetic surgery
done on their nose. The procedure, called rhinoplasty,
occasionally damages the septum’s blood supply.



Contracting certain diseases. Several diseases—
typhoid, syphilis, systemic lupus erythematosus, and
tuberculosis—can infect this tissue and destroy it.



Being exposed to harmful vapors. Toxic air pollutantlike acid fumes, phosphorus, and copper vapor—
and sometimes even cortisone sprays—can destroy
nasal tissue.

ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
Better Hearing Institute. 515 King Street, Suite 420,
Alexandria, VA 22314. (703) 684-3391.

Carol A. Turkington

Perforated septum
Definition
A perforated septum is a hole in the nasal septum,
the vertical plane of tissue that separates the nostrils.

Description
The nasal septum is a thin structure in the middle
of the nose. In front, it is cartilage, further back it is
bone. On either side, it is covered with mucus membranes. The cartilage depends upon the blood vessels
in the mucus membranes on either side for its nutrition.
If that blood supply is shut off, the cartilage dies,
producing a hole or perforation.

Causes and symptoms
There are several causes of a perforated septum.




Wearing ornaments in the nose. To hang an ornament from the middle of the nose requires that the
tissue directly in front of the septal cartilage be
pierced or perforated.
Sniffing cocaine. Cocaine is a potent vasoconstrictor,
which means that it causes small blood vessels to

2834

Perforation is not serious. It causes irritation,
mostly complaints of dryness and crusting.
Sometimes air blowing past it whistles. Picking at the
crusts can cause bleeding.

Treatment
Surgical repair is not difficult. The surgeon may
devise a plastic button that fits exactly into the defect
and stays in place like a collar button.

Alternative treatment
Saline nasal sprays may be sufficient to control
symptoms and prevent the need for surgery.

Prevention
Nosebleeds from the septum can usually be controlled with pinching. Vaginal estrogen cream has also
been used successfully to toughen the blood vessels.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Ballenger, John Jacob. Disorders of the Nose, Throat, Ear,
Head, and Neck. Philadelphia: Lea & Febiger, 1991.

J. Ricker Polsdorfer, MD

Whenever possible, an echocardiogram (ultrasound test) should be performed to confirm the presence of the pericardial effusion and to guide the
pericardiocentesis needle during the procedure.
Because of the risk of accidental puncture to major
arteries or organs in pericardiocentesis, surgical drainage may be a preferred treatment option for pericardial effusion in non-emergency situations.

Description

Pericardiocentesis
Definition
Pericardiocentesis is the removal by needle of
pericardial fluid from the sac surrounding the heart
for diagnostic or therapeutic purposes.

Purpose
The pericardium, the sac (or membrane) that surrounds the heart muscle, normally contains a small
amount of fluid that cushions and lubricates the
heart as the heart expands and contracts. When too
much fluid gathers in the pericardial cavity, the space
between the pericardium and the outer layers of the
heart, a condition known as pericardial effusion
occurs. Abnormal amounts of fluid may result from:


pericarditis (caused by infection, inflammation)



trauma (producing blood in the pericardial sac)



surgery or other invasive procedures performed on
the heart



cancer (producing malignant effusions)



myocardial infarction, congestive heart failure



renal failure

Possible causes of pericarditis include chest
trauma, systemic infection (bacterial, viral, or fungal),
myocardial infarction (heart attack), or tuberculosis.
When pericarditis is suspected, pericardiocentesis may
be advisable in order to obtain a fluid sample for
laboratory analysis to identify the underlying cause
of the condition.
Pericardiocentesis is also used in emergency situations to remove excessive accumulations of blood or
fluid from the pericardial sac, such as with cardiac
tamponade. When fluid builds up too rapidly or excessively in the pericardial cavity, the resulting compression on the heart impairs the pumping action of the
vascular system. Cardiac tamponade is a life-threatening
condition that requires immediate treatment.
GALE ENCYCLOPEDIA OF MEDICINE

The patient’s vital signs are monitored throughout
the procedure, and an ECG tracing is continuously run.
If time allows, sedation is administered, the puncture
site is cleaned with an antiseptic iodine solution, and a
local anesthetic is injected into the skin to numb the
area. The patient is instructed to remain still. The physician performing pericardiocentesis will insert a syringe
with an attached cardiac needle slowly into the chest
wall until the needle tip reaches the pericardial sac. The
patient may experience a sensation of pressure as
the needle enters the membrane. When the needle is in
the correct position, the physician will aspirate, or withdraw, fluid from the pericardial sac.
When the procedure is performed for diagnostic
purposes, the fluid will be collected into specimen
tubes for laboratory analysis. If the pericardiocentesis
is performed to treat a cardiac tamponade or other
significant fluid build-up, a pericardial catheter may be
attached to the needle to allow for continuous drainage.
After the cardiac needle is removed, pressure is
applied to the puncture site for approximately five
minutes, and the site is then bandaged.

Preparation
Prior to pericardiocentesis, the test procedure is
explained to the patient, along with the risks and
possible complications involved, and the patient is
asked to sign an informed consent form. If the patient
is incapacitated, the same steps are followed with a
family member.
No special diet or fasting is required for the test.
After the patient changes into a hospital gown, an
intravenous line is inserted into a vein in the arm. The
IV will be used to administer sedation, and any required
medications or blood products. Leads for an electrocardiogram (ECG) tracing are attached to the patient’s
right and left arms and legs, and the fifth lead is
attached to the cardiac needle used for the procedure.
The patient is instructed to lie flat on the table, with the
upper body elevated to a 60 degree angle.
2835

Pericardiocentesis

Precautions

Resources

Pericarditis

KEY TERMS
Cardiac tamponade—Compression and restriction
of the heart that occurs when the pericardium fills
with blood or fluid. This increase in pressure outside the heart interferes with heart function and can
result in shock and/or death.
Catheter—A long, thin, flexible tube used to drain
or administer fluids.
Echocardiogram—An imaging test using high-frequency sound waves to obtain pictures of the heart
and surrounding tissues.
Electrocardiogram—A cardiac test that measures
the electrical activity of the heart.
Myocardium—The middle layer of the heart wall.
Pericardium—A double membranous sac that
envelops and protects the heart.

infectious organism such as staphylococcus aureus is a
sign of bacterial pericarditis. Excessive protein is present in cases of systemic lupus erythematosus or myocardial infarction (heart attack). An elevated white
blood count may point to a fungal infection. If the
patient has a hemorrhage, a cardiac rupture, or cancer, there may be blood in the pericardial fluid.
Resources
BOOKS

Weinstock, Doris et al. eds. ‘‘Body system Tests:
Cardiovascular System.’’ In Illustrated Guide to
Diagnostic Tests, 2nd edition. Springhouse, PA:
Springhouse Corporation, 1998.
ORGANIZATION

The American Heart Association. National Center. 7272
Greenville Avenue, Dallas, Texas 75231. (800) AHAUSA 1. <http://www.americanheart.org>.

Paula Anne Ford-Martin

Aftercare
The site of the puncture and any drainage catheter
should be checked regularly for signs of infection such
as redness and swelling. Blood pressure and pulse are
also monitored following the procedure. Patients who
experience continued bleeding or abnormal swelling of
the puncture site, sudden dizziness, difficulty breathing,
or chest pains in the days following a pericardiocentesis
procedure should seek immediate medical attention.

Risks
Pericardiocentesis is an invasive procedure,
and infection of the puncture site or pericardium is
always a risk. Possible complications include perforation of a major artery, lung, or liver. The myocardium,
the outer muscle layer of the heart, could also be
damaged if the cardiac needle is inserted too deeply.

Normal results
Normal pericardial fluid is clear to straw-colored
in appearance with no bacteria, blood, cancer cells or
pathogens. There is typically a minimal amount of the
fluid (10–50 ml) in the pericardial cavity.

Abnormal results
A large volume of pericardial fluid (over 50 ml)
indicates the presence of pericardial effusion.
Laboratory analysis of the fluid can aid in the diagnosis of the cause of pericarditis. The presence of an
2836

Pericarditis
Definition
Pericarditis is an inflammation of the two layers of
the thin, sac-like membrane that surrounds the heart.
This membrane is called the pericardium, so the term
pericarditis means inflammation of the pericardium.

Description
Pericarditis is fairly common. It affects approximately one in 1,000 people. The most common form is
caused by infection with a virus. People in their 20s
and 30s who have had a recent upper respiratory
infection are most likely to be affected, along with
men aged 20–50. One out of every four people who
have had pericarditis will get it again, but after two
years these relapses are less likely.

Causes and symptoms
The viruses that cause pericarditis include those
that cause influenza, polio, and rubella (German
measles). In children, the most common viruses that
cause pericarditis are the adenovirus and the cocksackievirus (which is most likely to affect children
during warmer weather).
Although pericarditis is usually caused by a virus, it
also can be caused by an injury to the heart or it can
GALE ENCYCLOPEDIA OF MEDICINE



There are several forms of pericarditis, depending
on the cause.
Acute pericarditis
This is caused by infection with a virus, bacteria,
or fungus—usually in the lungs and upper respiratory
tract. This form of the disease causes a sharp, severe
pain that starts in the region of the breastbone. If the
pericarditis is caused by a bacteria, it is called bacterial
or purulent pericarditis.
Cardiac tamponade
Sometimes fluid collects between the heart and the
pericardium. This is called pericardial effusion, and
may lead to a condition called cardiac tamponade.
When the fluid accumulates, it can squeeze the heart
and prevent it from filling with blood. This keeps the
rest of the body from getting the necessary supply of
oxygen and can cause dangerously low blood pressure.
A cardiac tamponade can happen when the chest is
injured during surgery, radiation therapy, or an accident. Cardiac tamponade is a serious medical emergency and must be treated immediately.
Constrictive pericarditis
When the pericardium is scarred or thickened, the
heart has difficulty contracting. This is because the
pericardium has shrunken or tightened around
the heart, constricting the muscle’s heart movement.
This usually occurs as a result of tuberculosis, which
now is rarely found in the United States, except in
immigrant, AIDS, and prison populations.
Symptoms of pericarditis
Symptoms likely to be associated with pericarditis
include:


rapid breathing



breathlessness



dry cough



fever and chills



weakness



broken blood vessels (hemorrhages) in the mucus
membrane of the eyes, the back, the chest, fingers,
and toes



feelings of anxiety

GALE ENCYCLOPEDIA OF MEDICINE

A sharp or dull pain that starts in the front of the
chest under the breastbone and radiates to the left
side of the neck, upper abdomen, and left shoulder
the pain is less intense when the patient sits up or
leans forward and worsens when lying down; it may
worsen with a deep breath, like pleurisy, which may
accompany pericarditis

In cardiac tamponade, neck veins may be swollen
and blood pressure may be very low.

Diagnosis
The heart of a person with pericarditis is likely to
produce a grating sound (friction rub) when heard
through a stethoscope. This sound occurs because
the roughened pericardium surfaces are rubbing
against each other.
The following tests will also help diagnose pericarditis and what is causing it:


electrocardiograph (ECG) and echocardiogram to
distinguish between pericarditis and a heart attack.



x ray to show the traditional ‘‘water bottle’’ shadow
around the heart that is often seen in pericarditis
where there is a sufficient fluid build up.



computed tomography scan (CT scan) of the chest.



heart catheterization to view the heart’s chambers
and valves.



pericardiocentesis to test for viruses, bacteria, fungus,
cancer, and tuberculosis.



blood tests such as LDH and CPK to measure cardiac enzymes and distinguish between a heart attack
and pericarditis, as well as a complete blood count
(CBC) to look for infection.

Treatment
Since most pericarditis is caused by a virus and will
heal naturally, there is no specific, curative treatment.
Ordinary antibiotics do not work against viruses.
Pericarditis that comes from a virus usually clears up
in two weeks to three months. Medications may be used
to reduce inflammation, however. They include nonsteroidal anti-inflammatory drugs (NSAIDs), such as
ibuprofen and aspirin. Corticosteroids are helpful if
the pericarditis was caused by a heart attack or systemic
lupus erythematosus. Analgesics (painkillers such as
aspirin or acetaminophen) also may be given.
If the pericarditis recurs, removal of all or part of
the pericardium (pericardiectomy) may be necessary.
In the case of constrictive pericarditis, the pericardiectomy may be necessary to remove the stiffened
2837

Pericarditis

follow a heart attack. It may also be caused by certain
inflammatory diseases such as rheumatoid arthritis or
systemic lupus erythematosus. Bacteria, fungi, parasites,
tuberculosis, cancer or kidney failure may also affect the
pericardium. Sometimes the cause is unknown.

Pericarditis

Pericardium

Fluid in
pericardial sac

Cardiac tamponade occurs when fluid collects in the pericardial sac between the heart and the surrounding pericardium.
A medical emergency, cardiac tamponade deprives the body of oxygen and requires immediate treatment. (Illustration by
Electronic Illustrators Group.)

KEY TERMS
Computed tomography (CT) scan—A CT scan uses
x rays to scan the body from many angles. A computer compiles the x rays into a picture of the area
being studied. The images are viewed on a monitor
and printed-out.
Echocardiogram—An echocardiogram bounces
sound waves off the heart to create a picture of its
chambers and valves.
Electrocardiogram (ECG)—An ECG is a test to
measure electrical activity in the heart.
Heart catheterization—A heart catheterization is
used to view the heart’s chamber and valves. A tube
(catheter) is inserted into an artery, usually in the
groin. A dye is then put into the artery through the
tube. The dye makes its way to the heart to create an
image of the heart on x-ray film. The image is
photographed and stored for further examination.
Pericardiocentesis—Pericardiocentesis is a procedure used to test for viruses, bacteria, and fungus. The
physician puts a small tube through the skin, directly
into the pericardial sac, and withdraws fluid. The fluid
then is tested for viruses, bacteria, and fungus.
Pericardium—The pericardium is the thin, sac-like
membrane that surrounds the heart. It has two layers:
the serous pericardium and the fibrous pericardium.
2838

parts of the pericardium that are preventing the heart
from beating correctly.
If a cardiac tamponade is present, it may be necessary to drain excess fluid from the pericardium.
Pericardiocentesis, the same procedure used for testing, will be used to withdraw the fluid.
For most people, home care with rest and medications to relieve pain are sufficient. A warm heating pad
or compress also may help relieve pain. Sitting in an
upright position and bending forward helps relieve
discomfort. A person with pericarditis may also be
kept in bed, with the head of the bed elevated to reduce
the heart’s need to work hard as it pumps blood. Along
with painkillers and antibiotics, diuretic drugs (‘‘water
pills’’) to reduce fluids may also be used judiciously.

Prognosis
Prognosis is good. Most people recover within
three weeks to several months and do not need any
additional treatment.

Prevention
There is no way to prevent pericarditis, but a
healthy lifestyle with proper nutrition and exercise will
help keep the body’s immune system strong and more
likely to fight off invading microorganisms.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300 or (800) 242-8721. inquire@
heart.org. <http://www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Christine Kuehn Kelly

Perinatal infection
Definition
An infection caused by a bacteria or virus that can
be passed from a mother to her baby during pregnancy
or delivery is called a perinatal infection.

Description
Perinatal infections include bacterial or viral illnesses that can be passed from a mother to her baby
either while the baby is still in the uterus, during the
delivery process, or shortly after birth. Maternal infection can, in some cases, cause complications at birth.
The mother may or may not experience active symptoms of the infection during the pregnancy. The most
serious and most common perinatal infections, and
the impact of these diseases on the mother and infant,
are discussed below in alphabetical order. It is important to note that men can become infected and can
transmit many of these infections to other women. The
sexual partners of women who have these infections
also should seek medical treatment.

Causes and symptoms
Chlamydia
Chlamydia trachomatis is the most common bacterial sexually transmitted disease in the United States,
causing more than 4 million infections each year. The
majority of women with chlamydial infection experience no obvious symptoms. The infection affects the
reproductive tract and causes pelvic inflammatory disease, infertility, and ectopic pregnancy (the fertilized
egg implants somewhere other than in the uterus).
This infection can cause premature rupture of the
membranes and early labor. It can be passed to the
infant during delivery and can cause ophthalmia neonatorum (an eye infection) within the first month of
GALE ENCYCLOPEDIA OF MEDICINE

life and pneumonia within one to three months of age.
Symptoms of chlamydial pneumonia are a repetitive
cough and rapid breathing. Wheezing is rare and the
infant does not develop a fever.
Cytomegalovirus
Cytomegalovirus (CMV) is a common virus in the
herpes virus family. It is found in saliva, urine, and
other body fluids and can be spread through sexual
contact or other more casual forms of physical contact
like kissing. In adults, CMV may cause mild symptoms of swollen lymph glands, fever, and fatigue.
Many people who carry the virus experience no symptoms at all. Infants can become infected with CMV
while still in the uterus if the mother becomes infected
or develops a recurrence of the infection during pregnancy. Most infants exposed to CMV before birth
develop normally and do not show any symptoms.
As many as 6,000 infants who were exposed to CMV
before birth are born with serious complications each
year. CMV interferes with normal fetal development
and can cause mental retardation, blindness, deafness,
or epilepsy in these infants.
Genital herpes
Genital herpes, which is usually caused by herpes
simplex virus type 2 (HSV-2), is a sexually transmitted
disease that causes painful sores on the genitals.
Women who have their first outbreak of genital herpes
during pregnancy are at high risk of miscarriage or
delivering a low birth weight baby. The infection can
be passed to the infant at the time of delivery if the
mother has an active sore. The most serious risk to the
infant is the possibility of developing HSV-2 encephalitis, an inflammation of the brain, with symptoms of
irritability and poor feeding.
Hepatitis B
Hepatitis B is a contagious virus that causes liver
damage and is a leading cause of chronic liver disease
and cirrhosis. Approximately 20,000 infants are born
each year to mothers who test positive for the hepatitis
B virus. These infants are at high risk for developing
hepatitis B infection through exposure to their
mothers blood during delivery.
Human immunodeficiency virus (HIV)
Human immunodeficiency virus (HIV) is a serious,
contagious virus that causes acquired immunodeficiency syndrome (AIDS). About one-fourth of pregnant women with HIV pass the infection on to their
2839

Perinatal infection

Resources

Perinatal infection

newborn infants. An infant with HIV usually develops
AIDS and dies before the age of two.
Human papillomavirus
Human papillomavirus (HPV) is a sexually transmitted disease that causes genital warts and can
increase the risk of developing some cancers. HPV
appears to be transferred from the mother to the infant
during the birth process.
Rubella (German measles)
Rubella is a virus that causes German measles,
an illness that includes rash, fever, and symptoms
of an upper respiratory tract infection. Most people are exposed to rubella during childhood and
develop antibodies to the virus so they will never
get it again. Rubella infection during early pregnancy can pass through the placenta to the developing infant and cause serious birth defects
including heart abnormalities, mental retardation,
blindness, and deafness.
Streptococcus
Group B streptococcus (GBS) infection is the
most common bacterial cause of infection and
death in newborn infants. Although rates have
declined in the United States since the introduction
of antibiotics to at-risk women during labor in the
1980s, about 1,600 cases and 80 newborn deaths
still occur each year. In women, GBS can cause
vaginitis and urinary tract infections. Both infections can cause premature birth and the bacteria
can be transferred to the infant in the uterus or
during delivery. GBS causes pneumonia, meningitis, and other serious infections in infants.
Syphilis
Syphilis is a sexually transmitted bacterial infection that can be transferred from a mother to an infant
through the placenta before birth. Up to 50% of
infants born to mothers with syphilis will be premature, stillborn, or will die shortly after birth. Infected
infants may have severe birth defects. Those infants
who survive infancy may develop symptoms of syphilis up to two years later.

the third trimester of the pregnancy. Chlamydial cell
cultures take three to seven days to grow but many
laboratories are not equipped to run the tests necessary to confirm the diagnosis.
Cytomegalovirus
Past or recent infection with CMV can be identified by antibody tests and CMV can be grown from
body fluids.
Genital herpes
The appearance of a genital sore is enough to
suspect an outbreak of genital herpes. The sore can
be cultured and tested to confirm that HSV-2 is
present.
Hepatitis B
A blood test can be used to screen pregnant
women for the hepatitis B surface antigen (HBsAg)
in prenatal health programs.
Human immunodeficiency virus (HIV)
HIV can be detected using a blood test and is part
of most prenatal screening programs.
Human papillomavirus
HPV causes the growth of warts in the genital
area. The wart tissue can be removed with a scalpel
and tested to determine what type of HPV virus caused
the infection.
Rubella (German measles)
Pregnant women are usually tested for antibodies to rubella, which would indicate that they
have been previously exposed to the virus and
therefore would not develop infection during pregnancy if exposed.
Streptococcus
GBS can be detected by a vaginal or rectal swab
culture, and sometimes from a urine culture. Blood
tests can be used to confirm GBS infection in infants
who exhibit symptoms.

Diagnosis
Chlamydia
Chlamydial bacteria can be diagnosed by taking a
cotton swab sample of the cervix and vagina during
2840

Syphilis
Pregnant women are usually tested for syphilis as
part of the prenatal screening.
GALE ENCYCLOPEDIA OF MEDICINE

Chlamydia
Pregnant women can be treated during the third
trimester with oral erythromycin, for seven–14 days
depending on the dose used. Newborn infants can be
treated with erythromycin liquid for 10–14 days at a
dosage determined by their body weight.

electrocauterization (burning), or surgical excision
(cutting) of the warts. Some medications (imiquimod
5% cream, podophyllin, trichloroacetic acid or topical
5-fluorouracil) can be applied to help dissolve genital
warts. Cesarean delivery rather than vaginal delivery
seems to reduce the risk of transmission of HPV from
mothers to infants.
Rubella (German measles)

Cytomegalovirus
No drugs or vaccines are currently available for
prevention or treatment of CMV.
Genital herpes
The antiviral drugs acyclovir or famciclovir can be
administered to the mother during pregnancy. Little is
known about the risks of these drugs to the fetus,
however, the risk of birth defects does not seem to be
any higher than for women who do not take these
medications. Infants with suspected HSV-2 can be
treated with acyclovir. Delivery of the infant by cesarean section is recommended if the mother has an active
case of genital herpes.
Hepatitis B
Infants born to mothers who test positive to the
HBsAg test should be treated with hepatitis B immune
globulin at birth to give them immediate protection
against developing hepatitis B. These infants, as well
as all infants, should also receive a series of three
hepatitis B vaccine injections as part of their routine
immunizations.
Human immunodeficiency virus (HIV)
Recent studies have shown that prenatal care
and HIV testing before delivery are major opportunities to prevent perinatal HIV infection. Pregnant
women with HIV should be treated as early in the
pregnancy as possible with zidovudine (AZT).
Other newer drugs designed to treat HIV/AIDS
also may be used during pregnancy with the knowledge that these drugs may have unknown effects on
the infant. The risks and benefits of such treatments
need to be discussed. Infants born with HIV should
receive aggressive drug treatment to prevent development of AIDS.
Human papillomavirus
Genital warts are very difficult to treat and frequently recur even after treatment. They can be
removed by cryotherapy (freezing), laser or
GALE ENCYCLOPEDIA OF MEDICINE

No treatment is available. Some health care providers may recommend giving the mother an injection
of immune globulin (to boost the immune system to
fight off the virus) if she is exposed to rubella early in
the pregnancy. However, no evidence to support the
use of these injections exists. Exposure to rubella early
in pregnancy poses a high risk that the infant will have
serious birth defects. Termination of the pregnancy
may be considered. Women who have not been previously exposed to rubella will usually be vaccinated
immediately after the first pregnancy to protect
infants of future pregnancies.
Streptococcus
Pregnant women diagnosed with GBS late in the
pregnancy should be treated with antibiotics injected
intravenously to prevent premature labor. In 2003, the
Centers for Disease Control and Prevention (CDC)
issued revised guidelines for preventing perinatal
GBS disease. They began recommending that women
not only be tested as soon as they learn of their pregnancy, but again at 35 to 37 weeks gestation. The
CDC also recommended updated prophylaxis regimens for women with penicillin allergies, as well as
new guidelines for patients with threatened preterm
deliveries and other new recommendations. If transmission of GBS to the newborn infant already is suspected or if the baby develops symptoms of infection,
infants often are treated with antibiotics.
Syphilis
Antibiotic therapy, usually penicillin, given early
in the pregnancy can be used to treat the infection and
may prevent transmission to the infant.

Prognosis
Chlamydia
Without treatment, the most serious consequences of chlamydial infection are related to complications of premature delivery. Treatment of the
mother with antibiotics during the third trimester
can prevent premature delivery and the transfer of
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Perinatal infection

Treatment

Perinatal infection

Human papillomavirus

KEY TERMS
Cesarean section—A surgical procedure in which
an incision is made in a woman’s abdomen to
deliver the infant from the uterus.
Ectopic pregnancy—A condition that ends in miscarriage, in which the fertilized ovum attaches
somewhere other than in the uterus (for example
in the fallopian tube or abdomen).
Encephalitis—Inflammation or swelling of the
brain.
Perinatal—The period of time around the time of
pregnancy and delivery.
Pneumonia—An infection and inflammation of the
lungs that usually causes shortness of breath,
cough, fever, and chest pain.

Once infected with HPV, there is a lifelong risk of
developing warts and an increased risk of some
cancers.
Rubella (German measles)
Infants exposed to rubella virus in the uterus are
at high risk for severe birth defects including heart
defects, blindness, and deafness.
Streptococcus
Infection of the urinary tract or genital tract of
pregnant women can cause premature birth. Infants
infected with GBS can develop serious, life-threatening infections.
Syphilis

the infection to the baby. Infants treated with antibiotics for eye infection or pneumonia generally
recover.
Cytomegalovirus
The chance for recovery after exposure to CMV is
very good for both the mother and the infant.
Exposure to CMV can be serious and even life threatening for mothers and infants whose immune systems
are compromised, for example those receiving chemotherapy or who have HIV/AIDS. Those infants
who develop birth defects after CMV exposure may
have serious, lifelong complications.
Genital herpes
Once a woman or infant is infected, outbreaks of
genital herpes sores can recur at any point during their
lifetimes.

Premature birth, birth defects, or the development
of serious syphilis symptoms is likely to occur in
untreated pregnant women.

Prevention
Use of a barrier method of contraceptive (condom)
can prevent transmission of some of the infections.
Intravenous drug use and sexual intercourse with
infected partners increases the risks of exposure to
most of these infections. Pregnant women can be
tested for many of the bacterial or viral infections
described; however, effective treatment may not be
available to protect the infant. New studies show
that a woman’s nutritional status may contribute to
her ability to fight off infections, particularly in cases
of malnutrition. Proper prenatal care may improve
outcomes and prevent some infections.
Resources
PERIODICALS

Hepatitis B
Infants treated at birth with immune globulin
and the series of vaccinations will be protected from
development of hepatitis B infection. Infants infected
with hepatitis B develop a chronic, mild form of
hepatitis and are at increased risk for developing
liver disease.
Human immunodeficiency virus (HIV)
Treatment with AZT during pregnancy significantly reduces the chance that the infant will be
infected with HIV from the mother.
2842

Goldenberg, Robert L. ‘‘The Plausibility of Micronutrient
Deficiency in Relationship to Perinatal Infection.’’ The
Journal of Nutrition May 2003: 1645S.
Morantz, Carrie A. ‘‘CDC Updates Guidelines for
Prevention of Perinatal Group B Streptococcal
Disease.’’ American Family Physician March 1,
2003: 1121.
Peters, Vicki, et al. ‘‘Missed Opportunities for Perinatal HIV
Prevention Among HIV-exposed Infants Born 1996–
2000, Pediatric Spectrum of HIV Disease Cohort.’’
Pediatrics May 2003: S1186.

Altha Roberts Edgren
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Periodic paralysis
Definition
Periodic paralysis (PP) is the name for several
rare, inherited muscle disorders marked by temporary
weakness, especially following rest, sleep, or exercise.

Description
Periodic paralysis disorders are genetic disorders
that affect muscle strength. There are two major
forms, hypokalemic and hyperkalemic, each caused
by defects in different genes.
In hypokalemic PP, the level of potassium in the
blood falls in the early stages of a paralytic attack, while
in hyperkalemic PP, it rises slightly or is normal. (The
root of both words, ‘‘kali,’’ refers to potassium.)
Hyperkalemic PP is also called potassium-sensitive PP.

Causes and symptoms
Causes
Both forms of PP are caused by inheritance of
defective genes. Both genes are dominant, meaning
that only one copy of the defective gene is needed for
a person to develop the disease. A parent with the gene
has a 50% chance of passing it along to each offspring,
and the likelihood of passing it on is unaffected by the
results of previous pregnancies.
The gene for hypokalemic PP is present equally in
both sexes, but leads to noticeable symptoms more
often in men than in women. The normal gene is
responsible for a muscle protein controlling the flow
of calcium during muscle contraction.
The gene for hyperkalemic PP affects virtually all
who inherit it, with no difference in male-vs.-female
expression. The normal gene is responsible for a muscle protein controlling the flow of sodium during muscle contraction.
Symptoms
The attacks of weakness in hypokalemic PP
usually begin in late childhood or early adolescence
and often become less frequent during middle age. The
majority of patients develop symptoms before age 16.
Since they begin in the school years, the symptoms of
hypokalemic PP are often first seen during physical
education classes or after-school sports, and may be
mistaken for laziness, or lack of interest on the part of
the child.
GALE ENCYCLOPEDIA OF MEDICINE



strenuous exercise followed by a short period of rest



large meals, especially ones rich in carbohydrates or
salt



emotional stress



alcohol use



infection



pregnancy

The weakness from a particular attack may last
from several hours to as long as several days, and may
be localized to a particular limb, or might involve the
entire body.
The attacks of weakness of hyperkalemic PP
usually begin in infancy or early childhood, and may
become less severe later in life. As in the hypokalemic
form, attacks are brought on by stress, pregnancy, and
exercise followed by rest. In contrast, though, hyperkalemic attacks are not associated with a heavy meal
but rather with missing a meal, with high potassium
intake, or use of glucocorticoid drugs such as prednisone. (Glucocorticoids are a group of steroids that
regulate metabolism and affect muscle tone.)
Weakness usually lasts less than three hours, and
often persists for only several minutes. The attacks are
usually less severe, but more frequent, than those of
the hypokalemic form. Weakness usually progresses
from the lower limbs to the upper, and may involve the
facial muscles as well.

Diagnosis
Diagnosis of either form of PP begins with a careful medical history and a complete physical and neurological exam. A family medical history may reveal
other affected relatives. Blood and urine tests done at
the onset of an attack show whether there are elevated
or depressed levels of potassium. Electrical tests of
muscle and a muscle biopsy show characteristic
changes.
Challenge tests, to aid in diagnosis, differ for the
two forms. In hypokalemic PP, an attack of weakness
can be brought on by administration of glucose and
insulin, with exercise if necessary. An attack of hyperkalemic PP can be induced with administration of
potassium after exercise during fasting. These tests
are potentially hazardous and require careful
monitoring.
Genetic tests are available at some research centers and are usually recommended for patients with a
known family history. However, the number of
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Periodic paralysis

Attacks are most commonly brought on by:

Periodontal disease

Resources

KEY TERMS
Gene—A biologic unit of heredity transmitted from
parents to offspring.

different possible mutations leading to each form is
too great to allow a single comprehensive test for
either form, thus limiting the usefulness of genetic
testing.

ORGANIZATIONS

Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson, AZ 85718. (800) 572-1717. <http://
www.mdausa.org>.
Periodic Paralysis Association. 5225 Canyon Crest Drive
#71-351, Riverside, CA 92507. (909) 781-4401. <http://
www.periodicparalysis.org>.

Richard Robinson

Treatment
Severe respiratory weakness from hypokalemic
PP may require intensive care to ensure adequate ventilation. Potassium chloride may be given by mouth or
intravenously to normalize blood levels.
Attacks requiring treatment are much less common in hyperkalemic PP. Glucose and insulin may be
prescribed. Eating carbohydrates may also relieve
attacks.

Periodontal disease
Definition
Periodontal diseases are a group of diseases that
affect the tissues that support and anchor the teeth.
Left untreated, periodontal disease results in the
destruction of the gums, alveolar bone (the part of
the jaws where the teeth arise), and the outer layer of
the tooth root.

Prognosis
Most patients learn to prevent their attacks well
enough that no significant deterioration in the quality
of life occurs. Strenuous exercise must be avoided,
however. Attacks often lessen in severity and frequency during middle age. Frequent or severe attacks
increase the likelihood of permanent residual weakness, a risk in both forms of periodic paralysis.

Prevention
There is no way to prevent the occurrence of either
disease in a person with the gene for the disease. The
likelihood of an attack of either form of PP may be
lessened by avoiding the triggers (the events or combinations of circumstances which cause an attack)
for each.
Hypokalemic PP attacks may be prevented with
use of acetazolamide (or another carbonic anhydrase
inhibitor drug) or a diuretic to help retain potassium in
the bloodstream. These attacks may also be prevented
by avoiding such triggers as salty food, large meals, a
high-carbohydrate diet, and strenuous exercise.
Attacks of hyperkalemic PP may be prevented
with frequent small meals high in carbohydrates, and
the avoidance of foods high in potassium such as
orange juice or bananas. Acetazolamide or thiazide
(a diuretic) may be prescribed.
2844

Description
Periodontal disease is usually seen as a chronic
inflammatory disease. An acute infection of the periodontal tissue may occur, but is not usually reported
to the dentist. The tissues that are involved in periodontal diseases are the gums, which include the gingiva,
periodontal ligament, cementum, and alveolar bone.
The gingiva is a pink-colored mucus membrane that
covers parts of the teeth and the alveolar bone. The
periodontal ligament is the main part of the gums. The
cementum is a calcified structure that covers the lower
parts of the teeth. The alveolar bone is a set of ridges
from the jaw bones (maxillary and mandible) in which
the teeth are embedded. The main area involved in
periodontal disease is the gingival sulcus, a pocket
between the teeth and the gums. Several distinct
forms of periodontal disease are known. These are
gingivitis, acute necrotizing ulcerative gingivitis,
adult periodontitis, and localized juvenile periodontitis. Although periodontal disease is thought to be
widespread, serious cases of periodontitis are not common. Gingivitis is also one of the early signs of leukemia in some children.
Gingivitis
Gingivitis is an inflammation of the outermost
soft tissue of the gums. The gingivae become red and
GALE ENCYCLOPEDIA OF MEDICINE

Periodontal disease

inflamed, loose their normal shape, and bleed easily.
Gingivitis may remain a chronic disease for years without affecting other periodontal tissues. Chronic gingivitis may lead to a deepening of the gingival sulcus.
Acute necrotizing ulcerative gingivitis is mainly seen in
young adults. This form of gingivitis is characterized
by painful, bleeding gums, and death (necrosis) and
erosion of gingival tissue between the teeth. It is
thought that stress, malnutrition, fatigue, and poor
oral hygiene are among the causes for acute necrotizing ulcerative gingivitis.
Adult periodontitis
Adult periodontitis is the most serious form of the
periodontal diseases. It involves the gingiva, periodontal
ligament, and alveolar bone. A deep periodontal pocket
forms between the teeth, the cementum, and the gums.
Plaque, calculus, and debris from food and other sources
collect in the pocket. Without treatment, the periodontal
ligament can be destroyed and resorption of the alveolar
bone occurs. This allows the teeth to move more freely
and eventually results in the loss of teeth. Most cases of
adult periodontitis are chronic, but some cases occur in
episodes or periods of tissue destruction.
Localized juvenile periodontitis
Localized juvenile periodontitis is a less common
form of periodontal disease and is seen mainly in
young people. Primarily, localized juvenile periodontitis affects the molars and incisors. Among the distinctions that separate this form of periodontitis are
the low incidence of bacteria in the periodontal
pocket, minimal plaque formation, and mild
inflammation.
Herpetic gingivostomatitis
Herpes infection of the gums and other parts of the
mouth is called herpetic gingivostomatitis and is frequently grouped with periodontal diseases. The
infected areas of the gums turn red in color and have
whitish herpetic lesions. There are two principal differences between this form of periodontal diseases and
most other forms. Herpetic gingivostomatitis is caused
by a virus, Herpes simplex, not by bacteria, and the
viral infection tends to heal by itself in approximately
two weeks. Also, herpetic gingivostomatitis is infectious
to other people who come in contact with the herpes
lesions or saliva that contains virus from the lesion.
Pericoronitis
Pericoronitis is a condition found in children who
are in the process of producing molar teeth. The
GALE ENCYCLOPEDIA OF MEDICINE

An extreme case of juvenile periodontitis. (Custom Medical
Stock Photo. Reproduced by permission.)

disease is seen more frequently in the lower molar
teeth. As the molar emerges, a flap of gum still covers
the tooth. The flap of gum traps bacteria and food,
leading to a mild irritation. If the upper molar fully
emerges before the lower one, it may bite down on the
flap during chewing. This can increase the irritation of
the flap and lead to an infection. In bad cases, the
infection can spread to the neck and cheeks.
Desquamative gingivitis
Desquamative gingivitis occurs mainly in postmenopausal women. The cause of the disease is not
understood. The outer layers of the gums slough off,
leaving raw tissue and exposed nerves.
Trench mouth
Trench mouth is an acute, necrotizing (causing
tissue death), ulcerating (causing open sores) form of
gingivitis. It causes pain in the affected gums. Fever
and fatigue are usually present also. Trench mouth,
also known as Vincent’s disease, is a complication of
mild cases of gingivitis. Frequently, poor oral hygiene
is the main cause. Stress, an unbalanced diet, or lack of
sleep are frequent cofactors in the development of
trench mouth. This form of periodontal disease is
more common in people who smoke. The term ‘‘trench
mouth’’ was created in World War I, when the disease
was common in soldiers who lived in the trenches.
Symptoms of trench mouth appear suddenly. The
initial symptoms include painful gums and foul
breath. Gum tissue between teeth becomes infected
and dies, and starts to disappear. Often, what appears
to be remaining gum is dead tissue. Usually, the gums
bleed easily, especially when chewing. The pain can
increase to the point where eating and swallowing
become difficult. Inflammation or infection from
2845

Periodontal disease
Gingivitis, an inflammation of the gums, is a common periodontal disease. (Photograph by Edward H. Gill, Custom Medical
Stock Photo. Reproduced by permission.)

trench mouth can spread to nearby tissues of the face
and neck.
Periodontitis
Periodontitis is a condition in which gingivitis has
extended down around the tooth and into the supporting bone structure. Periodontitis is also called pyorrhea. Plaque and tarter buildup sometimes lead to the
formation of large pockets between the gums and
teeth. When this happens, anaerobic bacteria grow in
the pockets. The pockets eventually extend down
around the roots of the teeth where the bacteria
cause damage to the bone structure supporting the
teeth. The teeth become loose and tooth loss can
result. Some medical conditions are associated with
an increased likelihood of developing periodontitis.
These diseases include diabetes, Down syndrome,
Cohn’s disease, AIDS, and any disease that reduces
the number of white blood cells in the body for
extended periods of time.

Causes and symptoms
Several factors play a role in the development of
periodontal disease. The most important are age and
oral hygiene. The number and type of bacteria present
on the gingival tissues also play a role in the development of periodontal diseases. The presence of certain
species of bacteria in large enough numbers in the
gingival pocket and related areas correlates with the
development of periodontal disease. Also, removal of
the bacteria correlates with reduction or elimination of
disease. In most cases of periodontal disease, the bacteria remain in the periodontal pocket and do not
invade surrounding tissue.
2846

The mechanisms by which bacteria in the periodontal pocket cause tissue destruction in the surrounding region are not fully understood. Several bacterial
products that diffuse through tissue are thought to
play a role in disease formation. Bacterial endotoxin
is a toxin produced by some bacteria that can kill cells.
Studies show that the amount of endotoxin present
correlates with the severity of periodontal disease.
Other bacterial products include proteolytic enzymes,
molecules that digest protein found in cells, thereby
causing cell destruction. The immune response has
also been implicated in tissue destruction. As part of
the normal immune response, white blood cells enter
regions of inflammation to destroy bacteria. In the
process of destroying bacteria, periodontal tissue is
also destroyed.
Gingivitis usually results from inadequate oral
hygiene. Proper brushing of the teeth and flossing
decreases plaque buildup. The bacteria responsible
for causing gingivitis reside in the plaque. Plaque is a
sticky film that is largely made from bacteria. Tartar is
plaque that has hardened. Plaque can turn into tartar
in as little as three days if not brushed off. Tartar is
difficult to remove by brushing. Gingivitis can be
aggravated by hormones, and sometimes becomes
temporarily worse during pregnancy, puberty, and
when the patient is taking birth control pills.
Interestingly, some drugs used to treat other conditions can cause an overgrowth of the gingival tissue
that can result in gingivitis because plaque builds up
more easily. Drugs associated with this condition are
phenytoin, used to treat seizures; cyclosporin, given to
organ transplant patients to reduce the likelihood of
organ rejection; and calcium blockers, used to treat
several different heart conditions. Scurvy, a vitamin C
deficiency, and pellagra, a niacin deficiency, can also
lead to bleeding gums and gingivitis.
The initial symptoms of periodontitis are bleeding
and inflamed gums, and bad breath. Periodontitis follows cases of gingivitis, which may not be severe
enough to cause a patient to seek dental help.
Although the symptoms of periodontitis are also
seen in other forms of periodontal diseases, the key
characteristic in periodontitis is a large pocket that
forms between the teeth and gums. Another characteristic of periodontitis is that pain usually does not
develop until late in the disease, when a tooth loosens
or an abscess forms.

Diagnosis
Diagnosis is made by observation of infected
gums. Usually, a dentist is the person to diagnose
GALE ENCYCLOPEDIA OF MEDICINE

Gingivitis

Inflamed gum
Firm gums

Periodontal disease

Healthy Gums

Periodontitis

Plaque and tartar

Infected pocket

Pocket

Loss of ligament
and bone

Periodontal
ligament

Healthy gums support the teeth. When gingivitis goes untreated, the gums become weak and pockets form around the teeth.
Plaque and tartar build up in the pockets, the gum recedes, and periodontitis occurs. (Illustration by Argosy Inc.)

KEY TERMS
Anaerobic bacteria—Microorganisms that grow in
the absence of oxygen.
Inflammation—A painful redness and swelling of
an area of tissue in response to infection or injury.

and characterize the various types of periodontal disease. In cases such as acute herpetic gingivostomatitis,
there are characteristic herpetic lesions. Many of the
periodontal diseases are distinguished based on the
severity of the infection and the number and type of
tissues involved.
Diagnosis of periodontitis includes measuring the
size of the pockets formed between the gums and teeth.
Normal gingival pockets are shallow. If periodontal
disease is severe, jaw bone loss will be detected in x-ray
images of the teeth. If too much bone is lost, the teeth
become loose and can change position. This will also
be seen in x-ray images.

Treatment
Tartar can only be removed by professional dental
treatment. Following treatment, periodontal tissues
usually heal quickly. Gingivitis caused by vitamin
deficiencies is treated by administering the needed
vitamin. There are no useful drugs to treat herpetic
GALE ENCYCLOPEDIA OF MEDICINE

gingivostomatitis. Because of the pain associated with
the herpes lesions, patients may not brush their teeth
while the lesions are present. Herpes lesions heal by
themselves without treatment. After the herpetic
lesions have disappeared, the gums usually return to
normal if good oral hygiene is resumed. Pericoronitis
is treated by removing debris under the flap of gum
covering the molar. This operation is usually performed by a dentist. Surgery is used to remove molars
that are not likely to form properly.
Treatment for trench mouth starts with a complete
cleaning of the teeth, removal of all plaque, tartar, and
dead tissue on the gums. For the first few days after
cleaning, the patient uses hydrogen peroxide mouth
washes instead of brushing. After cleaning, the gum
tissue will be very raw and rinsing minimizes damage
to the gums that might be caused by the toothbrush.
For the first few days, the patient should visit the dentist
daily for checkups and then every second or third day
for the next two weeks. Occasionally, antibiotic treatment is used to supplement dental cleaning of the teeth
and gums. Surgery may be needed if the damage to the
gums is extensive and they do not heal properly.
Treatment of periodontitis requires professional
dental care. The pockets around the teeth must be
cleaned, and all tartar and plaque removed. In periodontitis, tartar and plaque can extend far down the
tooth root. Normal dental hygiene, brushing and
flossing, cannot reach deep enough to be effective in
treating periodontitis. In cases where pockets are very
deep (more than 0.25 in [0.64 cm] deep), surgery is
2847

Peripheral neuropathy

required to clean the pocket. This is performed in a
dental office. Sections of gum that are not likely to
reattach to the teeth may be removed to promote
healing by healthy sections of gum. Abscesses are
treated with a combination of antibiotics and surgery.
The antibiotics may be delivered directly to the
infected gum and bone tissues to ensure that high
concentrations of the antibiotic reach the infected
area. Abscess infections, especially of bone, are difficult to treat and require long term antibiotic treatments to prevent a reoccurrence of infection.

Prognosis
Periodontal diseases can be easily treated. The
gums usually heal and resume their normal shape
and function. In cases where they do not, prostheses
or surgery can restore most of the support for proper
functioning of the teeth.

Prevention
Most forms of periodontal disease can be prevented with good dental hygiene. Daily use of a toothbrush and flossing is sufficient to prevent most cases of
periodontal disease. Tartar control toothpastes help
prevent tartar formation, but do not remove tartar
once it has formed.
Resources
BOOKS

Gorbach, S. L., J. G. Bartlett, and N. R. Blacklow. Infectious
Diseases. 2nd ed. Philadelphia: W. B. Saunders Co.,1998.

John T. Lohr, PhD

Periodontitis see Periodontal disease
Periorbital cellulitis see Orbital and periorbital cellulitis
Peripheral arterial disease see Peripheral
vascular disease
Peripheral neuritis see Peripheral
neuropathy

Peripheral neuropathy
Definition
The term peripheral neuropathy encompasses a
wide range of disorders in which the nerves outside
2848

of the brain and spinal cord—peripheral nerves—have
been damaged. Peripheral neuropathy may also be
referred to as peripheral neuritis, or if many nerves
are involved, the terms polyneuropathy or polyneuritis may be used.

Description
Peripheral neuropathy is a widespread disorder,
and there are many underlying causes. Some of these
causes are common, such as diabetes, and others are
extremely rare, such as acrylamide poisoning and certain
inherited disorders. The most common worldwide cause
of peripheral neuropathy is leprosy. Leprosy is caused
by the bacterium Mycobacterium leprae, which attacks
the peripheral nerves of affected people. According to
statistics gathered by the World Health Organization, an
estimated 1.15 million people have leprosy worldwide.
Leprosy is extremely rare in the United States,
where diabetes is the most commonly known cause
of peripheral neuropathy. It has been estimated that
more than 17 million people in the United States and
Europe have diabetes-related polyneuropathy. Many
neuropathies are idiopathic, meaning that no known
cause can be found. The most common of the inherited
peripheral neuropathies in the United States is
Charcot-Marie-Tooth disease, which affects approximately 125,000 persons.
Another of the better known peripheral neuropathies is Guillain-Barré syndrome, which arises from
complications associated with viral illnesses, such as cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus (HIV), or bacterial infection, including
Campylobacter jejuni and Lyme disease. The worldwide
incidence rate is approximately 1.7 cases per 100,000
people annually. Other well-known causes of peripheral
neuropathies include chronic alcoholism, infection of
the varicella-zoster virus, botulism, and poliomyelitis.
Peripheral neuropathy may develop as a primary symptom, or it may be due to another disease. For example,
peripheral neuropathy is only one symptom of diseases
such as amyloid neuropathy, certain cancers, or inherited
neurologic disorders. Such diseases may affect the peripheral nervous system (PNS) and the central nervous
system (CNS), as well as other body tissues.
To understand peripheral neuropathy and its
underlying causes, it may be helpful to review the
structures and arrangement of the PNS.
Nerve cells and nerves
Nerve cells are the basic building block of the
nervous system. In the PNS, nerve cells can be
GALE ENCYCLOPEDIA OF MEDICINE

Certain nerve cell axons, such as the ones in the
PNS, are covered with a substance called myelin. The
myelin sheath may be compared to the plastic coating
on electrical wires–it is there both to protect the cells
and to prevent interference with the signals being
transmitted. Protection is also given by Schwann
cells, special cells within the nervous system that
wrap around both myelinated and unmyelinated
axons. The effect is similar to beads threaded on a
necklace.
Nerve cell axons leading to the same areas of the
body may be bundled together into nerves.
Continuing the comparison to electrical wires, nerves
may be compared to an electrical cord–the individual
components are coated in their own sheaths and then
encased together inside a larger protective covering.
Peripheral nervous system
The nervous system is classified into two parts: the
CNS and the PNS. The CNS is made up of the brain
and the spinal cord, and the PNS is composed of the
nerves that lead to or branch off from the CNS.
The peripheral nerves handle a diverse array of
functions in the body. This diversity is reflected in the
major divisions of the PNS–the afferent and the efferent divisions. The afferent division is in charge of
sending sensory information from the body to the
CNS. When afferent nerve cell endings, called receptors, are stimulated, they release neurotransmitters.
These neurotransmitters relay a signal to the brain,
which interprets it and reacts by releasing other
neurotransmitters.
Some of the neurotransmitters released by the
brain are directed at the efferent division of the PNS.
The efferent nerves control voluntary movements, such
as moving the arms and legs, and involuntary movements, such as making the heart pump blood. The
nerves controlling voluntary movements are called
motor nerves, and the nerves controlling involuntary
actions are referred to as autonomic nerves. The afferent and efferent divisions continually interact with each
other. For example, if a person were to touch a hot
stove, the receptors in the skin would transmit a message of heat and pain through the sensory nerves to the
GALE ENCYCLOPEDIA OF MEDICINE

brain. The message would be processed in the brain and
a reaction, such as pulling back the hand, would be
transmitted via a motor nerve.
Neuropathy
NERVE DAMAGE. When an individual has a peripheral neuropathy, nerves of the PNS have been
damaged. Nerve damage can arise from a number of
causes, such as disease, physical injury, poisoning, or
malnutrition. These agents may affect either afferent
or efferent nerves. Depending on the cause of damage,
the nerve cell axon, its protective myelin sheath, or
both may be injured or destroyed.
CLASSIFICATION. There are hundreds of peripheral neuropathies. Reflecting the scope of PNS activity, symptoms may involve sensory, motor, or
autonomic functions. To aid in diagnosis and treatment, the symptoms are classified into principal neuropathic syndromes based on the type of affected
nerves and how long symptoms have been developing.
Acute development refers to symptoms that have
appeared within days, and subacute refers to those
that have evolved over a number of weeks. Early
chronic symptoms are those that take months to a
few years to develop, and late chronic symptoms
have been present for several years.

The classification system is composed of six principal neuropathic syndromes, which are subdivided
into more specific categories. By narrowing down the
possible diagnoses in this way, specific medical tests
can be used more efficiently and effectively. The six
syndromes and a few associated causes are listed
below:


Acute motor paralysis, accompanied by variable problems with sensory and autonomic functions.
Neuropathies associated with this syndrome are
mainly accompanied by motor nerve problems, but
the sensory and autonomic nerves may also be
involved. Associated disorders include GuillainBarré syndrome, diphtheritic polyneuropathy, and
porphyritic neuropathy.



Subacute sensorimotor paralysis. The term sensorimotor refers to neuropathies that are mainly characterized by sensory symptoms, but also have a minor
component of motor nerve problems. Poisoning with
heavy metals (e.g., lead, mercury, and arsenic), chemicals, or drugs are linked to this syndrome.
Diabetes, Lyme disease, and malnutrition are also
possible causes.



Chronic sensorimotor paralysis. Physical symptoms may resemble those in the above syndrome,
but the time scale of symptom development is
2849

Peripheral neuropathy

threadlike–their width is microscopic, but their length
can be measured in feet. The long, spidery extensions
of nerve cells are called axons. When a nerve cell is
stimulated, by touch or pain, for example, the message
is carried along the axon, and neurotransmitters are
released within the cell. Neurotransmitters are chemicals within the nervous system that direct nerve cell
communication.

Peripheral neuropathy

extended. This syndrome encompasses neuropathies arising from cancers, diabetes, leprosy,
inherited neurologic and metabolic disorders,
and hypothyroidism.


Neuropathy associated with mitochondrial diseases. Mitochondria are organelles–structures
within cells–responsible for handling a cell’s energy
requirements. If the mitochondria are damaged or
destroyed, the cell’s energy requirements are not
met and it can die.



Recurrent or relapsing polyneuropathy. This syndrome covers neuropathies that affect several nerves
and may come and go, such as Guillain-Barré syndrome, porphyria, and chronic inflammatory
demyelinating polyneuropathy.



Mononeuropathy or plexopathy. Nerve damage
associated with this syndrome is limited to a single
nerve or a few closely associated nerves.
Neuropathies related to physical injury to the
nerve, such as carpal tunnel syndrome and sciatica,
are included in this syndrome.

Causes and symptoms
Typical symptoms of neuropathy are related to
the type of affected nerve. If a sensory nerve is
damaged, common symptoms include numbness, tingling in the area, a prickling sensation, or pain. Pain
associated with neuropathy can be quite intense and
may be described as cutting, stabbing, crushing, or
burning. In some cases, a nonpainful stimulus may
be perceived as excruciating or pain may be felt even
in the absence of a stimulus. Damage to a motor nerve
is usually indicated by weakness in the affected area. If
the problem with the motor nerve has continued over a
length of time, muscle shrinkage (atrophy) or lack
of muscle tone may be noticeable. Autonomic
nerve damage is most noticeable when an individual
stands upright and experiences problems such as lightheadedness or changes in blood pressure. Other indicators of autonomic nerve damage are lack of sweat,
tears, and saliva; constipation; urinary retention; and
impotence. In some cases, heart beat irregularities and
respiratory problems can develop.
Symptoms may appear over days, weeks,
months, or years. Their duration and the ultimate
outcome of the neuropathy are linked to the cause
of the nerve damage. Potential causes include diseases, physical injuries, poisoning, and malnutrition
or alcohol abuse. In some cases, neuropathy is not the
primary disorder, but a symptom of an underlying
disease.
2850

Disease
Diseases that cause peripheral neuropathies may
either be acquired or inherited; in some cases, it is
difficult to make that distinction. The diabetes-peripheral neuropathy link has been well established. A typical pattern of diabetes-associated neuropathic
symptoms includes sensory effects that first begin in
the feet. The associated pain or pins-and-needles,
burning, crawling, or prickling sensations form a typical ‘‘stocking’’ distribution in the feet and lower legs.
Other diabetic neuropathies affect the autonomic
nerves and have potentially fatal cardiovascular
complications.
Several other metabolic diseases have a strong
association with peripheral neuropathy. Uremia, or
chronic kidney failure, carries a 10–90% risk of eventually developing neuropathy, and there may be an
association between liver failure and peripheral neuropathy. Accumulation of lipids inside blood vessels
(atherosclerosis) can choke-off blood supply to certain
peripheral nerves. Without oxygen and nutrients, the
nerves slowly die. Mild polyneuropathy may develop
in persons with low thyroid hormone levels.
Individuals with abnormally enlarged skeletal extremities (acromegaly), caused by an overabundance
of growth hormone, may also develop mild
polyneuropathy.
Neuropathy can also result from severe vasculitides, a group of disorders in which blood vessels are
inflamed. When the blood vessels are inflamed or
damaged, blood supply to the nerve can be affected,
injuring the nerve.
Both viral and bacterial infections have been
implicated in peripheral neuropathy. Leprosy is
caused by the bacteria M. leprae, which directly attack
sensory nerves. Other bacterial illness may set the
stage for an immune-mediated attack on the nerves.
For example, one theory about Guillain-Barré syndrome involves complications following infection
with Campylobacter jejuni, a bacterium commonly
associated with food poisoning. This bacterium carries
a protein that closely resembles components of myelin.
The immune system launches an attack against the
bacteria; but, according to the theory, the immune
system confuses the myelin with the bacteria in some
cases and attacks the myelin sheath as well. The underlying cause of neuropathy associated with Lyme disease is unknown; the bacteria may either promote an
immune-mediated attack on the nerve or inflict
damage directly.
Infection with certain viruses is associated with
extremely painful sensory neuropathies. A primary
GALE ENCYCLOPEDIA OF MEDICINE

Several types of peripheral neuropathies are associated with inherited disorders. These inherited disorders may primarily involve the nervous system, or the
effects on the nervous system may be secondary to an
inherited metabolic disorder. Inherited neuropathies
can fall into several of the principal syndromes,
because symptoms may be sensory, motor, or autonomic. The inheritance patterns also vary, depending
on the specific disorder. The development of inherited
disorders is typically drawn out over several years and
may herald a degenerative condition–that is, a condition that becomes progressively worse over time. Even
among specific disorders, there may be a degree of
variability in inheritance patterns and symptoms.
For example, Charcot-Marie-Tooth disease is usually
inherited as an autosomal dominant disorder, but it
can be autosomal recessive or, in rare cases, linked to
the X chromosome. Its estimated frequency is
approximately one in 2,500 people. Age of onset and
sensory nerve involvement can vary between cases.
The main symptom is a degeneration of the motor
nerves in legs and arms, and resultant muscle atrophy.
Other inherited neuropathies have a distinctly metabolic component. For example, in familial amyloid
polyneuropathies, protein components that make up
the myelin are constructed and deposited incorrectly.
Physical injury
Accidental falls and mishaps during sports and
recreational activities are common causes of physical
injuries that can result in peripheral neuropathy. The
common types of injuries in these situations occur
from placing too much pressure on the nerve, exceeding the nerve’s capacity to stretch, blocking adequate
blood supply of oxygen and nutrients to the nerve, and
tearing the nerve. Pain may not always be immediately
noticeable, and obvious signs of damage may take a
while to develop.
These injuries usually affect one nerve or a group
of closely associated nerves. For example, a common
injury encountered in contact sports such as football is
GALE ENCYCLOPEDIA OF MEDICINE

the ‘‘burner,’’ or ‘‘stinger,’’ syndrome. Typically, a
stinger is caused by overstretching the main nerves
that span from the neck into the arm. Immediate
symptoms are numbness, tingling, and pain that travels down the arm, lasting only a minute or two. A
single incident of a stinger is not dangerous, but recurrences can eventually cause permanent motor and
sensory loss.
Poisoning
The poisons, or toxins, that cause peripheral neuropathy include drugs, industrial chemicals, and environmental toxins. Neuropathy that is caused by drugs
usually involves sensory nerves on both sides of the
body, particularly in the hands and feet, and pain is a
common symptom. Neuropathy is an unusual side
effect of medications; therefore, most people can use
these drugs safely. A few of the drugs that have been
linked with peripheral neuropathy include metronidazole, an antibiotic; phenytoin, an anticonvulsant; and
simvastatin, a cholesterol-lowering medication.
Certain industrial chemicals have been shown to
be poisonous to nerves (neurotoxic) following workrelated exposures. Chemicals such as acrylamide, allyl
chloride, and carbon disulfide have all been strongly
linked to development of peripheral neuropathy.
Organic compounds, such as N-hexane and toluene,
are also encountered in work-related settings, as well
as in glue-sniffing and solvent abuse. Either route of
exposure can produce severe sensorimotor neuropathy that develops rapidly.
Heavy metals are the third group of toxins that
cause peripheral neuropathy. Lead, arsenic, thallium,
and mercury usually are not toxic in their elemental
form, but rather as components in organic or inorganic compounds. The types of metal-induced neuropathies vary widely. Arsenic poisoning may mimic
Guillain-Barré syndrome; lead affects motor nerves
more than sensory nerves; thallium produces painful
sensorimotor neuropathy; and the effects of mercury
are seen in both the CNS and PNS.
Malnutrition and alcohol abuse
Burning, stabbing pains and numbness in the feet,
and sometimes in the hands, are distinguishing features of alcoholic neuropathy. The level of alcohol
consumption associated with this variety of peripheral
neuropathy has been estimated as approximately 3 L
of beer or 300 mL of liquor daily for three years.
However, it is unclear whether alcohol alone is responsible for the neuropathic symptoms, because chronic
alcoholism is strongly associated with malnutrition.
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Peripheral neuropathy

example of such a neuropathy is caused by shingles.
After a case of chickenpox, the causative virus, varicella-zoster virus, becomes inactive in sensory nerves.
Years later, the virus may be reactivated. Once reactivated, it attacks and destroys axons. Infection with
HIV is also associated with peripheral neuropathy,
but the type of neuropathy that develops can vary.
Some HIV-linked neuropathies are noted for myelin
destruction rather than axonal degradation. Also,
HIV infection is frequently accompanied by other
infections, both bacterial and viral, that are associated
with neuropathy.

Peripheral neuropathy

Malnutrition refers to an extreme lack of nutrients
in the diet. It is unknown precisely which nutrient
deficiencies cause peripheral neuropathies in alcoholics and famine and starvation patients, but it is
suspected that the B vitamins have a significant role.
For example, thiamine (vitamin B1) deficiency is the
cause of beriberi, a neuropathic disease characterized
by heart failure and painful polyneuropathy of sensory
nerves. Vitamin E deficiency seems to have a role in
both CNS and PNS neuropathy.

Diagnosis
Clinical symptoms can indicate peripheral neuropathy, but an exact diagnosis requires a combination
of medical history, medical tests, and possibly a process of exclusion. Certain symptoms can suggest a
diagnosis, but more information is commonly needed.
For example, painful, burning feet may be a symptom
of alcohol abuse, diabetes, HIV infection, or an underlying malignant tumor, among other causes. Without
further details, effective treatment would be difficult.
During a physical examination, an individual is
asked to describe the symptoms very carefully.
Detailed information about the location, nature, and
duration of symptoms can help exclude some causes or
even pinpoint the actual problem. The person’s medical history may also provide clues as to the cause,
because certain diseases and medications are linked
to specific peripheral neuropathies. A medical history
should also include information about diseases that
run in the family, because some peripheral neuropathies are genetically linked. Information about hobbies, recreational activities, alcohol consumption, and
work place activities can uncover possible injuries or
exposures to poisonous substances.
The physical examination also includes blood
tests, such as those that check levels of glucose and
creatinine to detect diabetes and kidney problems,
respectively. A blood count is also done to determine
levels of different blood cell types. Iron, vitamin B12,
and other factors may be measured as well, to rule out
malnutrition. More specific tests, such as an assay for
heavy metals or poisonous substances, or tests to
detect vasculitis, are not typically done unless there is
reason to suspect a particular cause.
An individual with neuropathy may be sent to a
doctor that specializes in nervous system disorders
(neurologist). By considering the results of the physical examination and observations of the referring doctor, the neurologist may be able to narrow down the
possible diagnoses. Additional tests, such as nerve
conduction studies and electromyography, which tests
2852

muscle reactions, can confirm that nerve damage has
occurred and may also be able to indicate the nature of
the damage. For example, some neuropathies are
characterized by destruction of the myelin. This type
of damage is shown by slowed nerve conduction. If the
axon itself has suffered damage, the nerve conduction
may be slowed, but it will also be diminished in
strength. Electromyography adds further information
by measuring nerve conduction and muscle response,
which determines whether the symptoms are due to a
neuropathy or to a muscle disorder.
In approximately 10% of peripheral neuropathy
cases, a nerve biopsy may be helpful. In this test, a
small part of the nerve is surgically removed and
examined under a microscope. This procedure is
usually the most helpful in confirming a suspected
diagnosis, rather than as a diagnostic procedure by
itself.

Treatment
Treat the cause
Attacking the underlying cause of the neuropathy
can prevent further nerve damage and may allow for a
better recovery. For example, in cases of bacterial infection such as leprosy or Lyme disease, antibiotics may be
given to destroy the infectious bacteria. Viral infections
are more difficult to treat, because antibiotics are not
effective against them. Neuropathies associated with
drugs, chemicals, and toxins are treated in part by
stopping exposure to the damaging agent. Chemicals
such as ethylenediaminetetraacetic acid (EDTA) are
used to help the body concentrate and excrete some
toxins. Diabetic neuropathies may be treated by gaining
better control of blood sugar levels, but chronic kidney
failure may require dialysis or even kidney transplant to
prevent or reduce nerve damage. In some cases, such as
compression injury or tumors, surgery may be considered to relieve pressure on a nerve.
In a crisis situation, as in the onset of GuillainBarré syndrome, plasma exchange, intravenous
immunoglobulin, and steroids may be given.
Intubation, in which a tube is inserted into the trachea
to maintain an open airway, and ventilation may be
required to support the respiratory system. Treatment
may focus more on symptom management than on
combating the underlying cause, at least until a definitive diagnosis has been made.
Supportive care and long-term therapy
Some peripheral neuropathies cannot be resolved
or require time for resolution. In these cases,
GALE ENCYCLOPEDIA OF MEDICINE

Afferent—Refers to peripheral nerves that transmit
signals to the spinal cord and the brain. These nerves
carry out sensory function.
Autonomic—Refers to peripheral nerves that carry
signals from the brain and that control involuntary
actions in the body, such as the beating of the heart.
Autosomal dominant or autosomal recessive—
Refers to the inheritance pattern of a gene on a
chromosome other than X or Y. Genes are inherited
in pairs–one gene from each parent. However, the
inheritance may not be equal, and one gene may
overshadow the other in determining the final form
of the encoded characteristic. The gene that overshadows the other is called the dominant gene; the
overshadowed gene is the recessive one.
Axon—A long, threadlike projection that is part of a
nerve cell.

if there is a disorder with the nerve or if the muscle is
not capable of responding.
Inheritance pattern—Refers to dominant or recessive inheritance.
Motor—Refers to peripheral nerves that control
voluntary movements, such as moving the arms
and legs.
Myelin—The protective coating on axons.
Nerve biopsy—A medical test in which a small portion of a damaged nerve is surgically removed and
examined under a microscope.
Nerve conduction—The speed and strength of a
signal being transmitted by nerve cells. Testing
these factors can reveal the nature of nerve injury,
such as damage to nerve cells or to the protective
myelin sheath.

Central nervous system (CNS)—The part of the nervous system that includes the brain and the spinal cord.
Efferent—Refers to peripheral nerves that carry signals away from the brain and spinal cord. These
nerves carry out motor and autonomic functions.
Electromyography—A medical test that assesses
nerve signals and muscle reactions. It can determine

Neurotransmitter—Chemicals within the nervous
system that transmit information from or between
nerve cells.

long-term monitoring and supportive care is necessary. Medical tests may be repeated to chart the progress of the neuropathy. If autonomic nerve
involvement is a concern, regular monitoring of the
cardiovascular system may be carried out.

regenerates. Nerve cells cannot be replaced if they
are killed, but they are capable of recovering from
damage. The extent of recovery is tied to the extent
of the damage and a person’s age and general health
status. Recovery can take weeks to years, because
neurons grow very slowly. Full recovery may not be
possible and it may also not be possible to determine
the prognosis at the outset.

Because pain is associated with many of the neuropathies, a pain management plan may need to be
mapped out, especially if the pain becomes chronic. As
in any chronic disease, narcotics are best avoided. Agents
that may be helpful in neuropathic pain include amitriptyline, carbamazepine, and capsaicin cream. Physical
therapy and physician-directed exercises can help maintain or improve function. In cases in which motor nerves
are affected, braces and other supportive equipment can
aid an individual’s ability to move about.

Prognosis
The outcome for peripheral neuropathy depends
heavily on the cause. Peripheral neuropathy ranges
from a reversible problem to a potentially fatal complication. In the best cases, a damaged nerve
GALE ENCYCLOPEDIA OF MEDICINE

Peripheral nervous system (PNS)—Nerves that are
outside of the brain and spinal cord.
Sensory—Refers to peripheral nerves that transmit
information from the senses to the brain.

If the neuropathy is a degenerative condition,
such as Charcot-Marie-Tooth disease, an individual’s
condition will become worse. There may be periods of
time when the disease seems to reach a plateau, but
cures have not yet been discovered for many of these
degenerative diseases. Therefore, continued symptoms, potentially worsening to disabilities are to be
expected.
A few peripheral neuropathies are eventually
fatal. Fatalities have been associated with some cases
of diphtheria, botulism, and others. Some diseases
associated with neuropathy may also be fatal, but the
ultimate cause of death is not necessarily related to the
neuropathy, such as with cancer.
2853

Peripheral neuropathy

KEY TERMS

Peripheral vascular disease

Prevention
Peripheral neuropathies are preventable only to
the extent that the underlying causes are preventable.
Steps that a person can take to prevent potential problems include vaccines against diseases that cause neuropathy, such as polio and diphtheria. Treatment for
physical injuries in a timely manner can help prevent
permanent or worsening damage to nerves.
Precautions when using certain chemicals and drugs
are well advised in order to prevent exposure to neurotoxic agents. Control of chronic diseases such as
diabetes may also reduce the chances of developing
peripheral neuropathy.
Although not a preventive measure, genetic
screening can serve as an early warning for potential
problems. Genetic screening is available for some
inherited conditions, but not all. In some cases, presence of a particular gene may not mean that a person
will necessarily develop the disease, because there may
be environmental and other components involved.
Resources
ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.
Myelin Project Headquarters. Suite 225, 2001 Pennsylvania
Ave., N.W., Washington, D.C. 20006-1850. (202)
452-8994. <http://www.myelin.org>.
Neuropathy Association. 60 E. 42nd St., Suite 942, New
York, NY 10165. (800) 247-6968. <http://
www.neuropathy.org/association.html>.

Julia Barrett

Peripheral vascular disease
Definition
Peripheral vascular disease is a narrowing of
blood vessels that restricts blood flow. It mostly occurs
in the legs, but is sometimes seen in the arms.

Description
Peripheral vascular disease includes a group of
diseases in which blood vessels become restricted or
blocked. Typically, the patient has peripheral vascular
disease from atherosclerosis. Atherosclerosis is a disease in which fatty plaques form in the inside walls of
blood vessels. Other processes, such as blood clots,
2854

further restrict blood flow in the blood vessels. Both
veins and arteries may be affected, but the disease is
usually arterial. All the symptoms and consequences
of peripheral vascular disease are related to restricted
blood flow. Peripheral vascular disease is a progressive
disease that can lead to gangrene of the affected area.
Peripheral vascular disease may also occur suddenly if
an embolism occurs or when a blot clot rapidly develops in a blood vessel already restricted by an atherosclerotic plaque, and the blood flow is quickly cut off.

Causes and symptoms
There are many causes of peripheral vascular disease. One major risk factor is smoking cigarettes.
Other diseases predispose patients to develop peripheral vascular disease. These include diabetes, Buerger’s
disease, hypertension, and Raynaud’s disease. The
main symptom is pain in the affected area. Early symptoms include an achy, tired sensation in the affected
muscles. Since this disease is seen mainly in the legs,
these sensations usually occur when walking. The
symptoms may disappear when resting. As the disease
becomes worse, symptoms occur even during light
exertion and, eventually, occur all the time, even at
rest. In the severe stages of the disease the leg and foot
may be cold to the touch and will feel numb. The skin
may become dry and scaly. If the leg is even slightly
injured, ulcers may form because, without a good
blood supply, proper healing can not take place. At
the most severe stage of the disease, when the blood
flow is greatly restricted, gangrene can develop in
those areas lacking blood supply. In some cases, peripheral vascular disease occurs suddenly. This happens when an embolism rapidly blocks blood flow to
a blood vessel. The patient will experience a sharp
pain. followed by a loss of sensation in the affected
area. The limb will become cold and numb, and loose
color or turn bluish.

Diagnosis
Peripheral vascular disease can be diagnosed by
comparing blood pressures taken above and below the
point of pain. The area below the pain (downstream
from the obstruction) will have a much lower or undetectable blood pressure reading. Doppler ultrasonography and angiography can also be used to diagnose
and define this disease.

Treatment
If the person is a smoker, they should stop smoking immediately. Exercise is essential to treating this
GALE ENCYCLOPEDIA OF MEDICINE

Embolism—The blockage of a blood vessel by air,
blood clot, or other foreign body.
Plaque—A deposit, usually of fatty material, on the
inside wall of a blood vessel.

disease. The patient should walk until pain appears,
rest until the pain disappears, and then resume walking. The amount of walking a patient can do should
increase gradually as the symptoms improve. Ideally,
the patient should walk 30–60 minutes per day.
Infections in the affected area should be treated
promptly. Surgery may be required to attempt to
treat clogged blood vessels. Limbs with gangrene
must be amputated to prevent the death of the patient.

Peritonitis may be primary (meaning that it occurs
spontaneously, and not as the result of some other
medical problem) or secondary (meaning that it results
from some other condition). It is most often due to
infection by bacteria, but may also be due to some kind
of a chemical irritant (such as spillage of acid from the
stomach, bile from the gall bladder and biliary tract, or
enzymes from the pancreas during the illness called
pancreatitis). Peritonitis has even been seen in patients
who develop a reaction to the cornstarch used to powder gloves worn during surgery. Peritonitis with no
evidence of bacteria, chemical irritant, or foreign
body has occurred in such diseases as systemic lupus
erythematosus, porphyria, and familial Mediterranean
fever. When the peritoneum is contaminated by blood,
the blood can both irritate the peritoneum and serve as
a source of bacteria to cause an infection. Blood may
leak into the abdomen due to a burst tubal pregnancy,
an injury, or bleeding after surgery.

Prognosis
The prognosis depends on the underlying disease
and the stage at which peripheral vascular disease is
discovered. Removal of risk factors, such as smoking,
should be done immediately. In many cases, peripheral vascular disease can be treated successfully but
coexisting cardiovascular problems may ultimately
prove to be fatal.
Resources
BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, editors. The
Heart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD

Peritoneal dialysis see Dialysis, kidney
Peritoneal endoscopy see Laparoscopy
Peritoneal fluid analysis see Paracentesis

Peritonitis
Definition
Peritonitis is an inflammation of the membrane
which lines the inside of the abdomen and all of the
internal organs. This membrane is called the
peritoneum.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Primary peritonitis usually occurs in people who
have an accumulation of fluid in their abdomens
(ascites). Ascites is a common complication of severe
cirrhosis of the liver (a disease in which the liver grows
increasingly scarred and dysfunctional). The fluid that
accumulates creates a good environment for the
growth of bacteria.
Secondary peritonitis most commonly occurs
when some other medical condition causes bacteria
to spill into the abdominal cavity. Bacteria are normal
residents of a healthy intestine, but they should have
no way to escape and enter the abdomen, where they
could cause an infection. Bacteria can infect the peritoneum due to conditions in which a hole (perforation) develops in the stomach (due to an ulcer eating its
way through the stomach wall) or intestine (due to a
large number of causes, including a ruptured appendix
or a ruptured diverticulum). Bacteria can infect the
peritoneum due to a severe case of pelvic inflammatory disease (a massive infection of the female organs,
including the uterus and fallopian tubes). Bacteria can
also escape into the abdominal cavity due to an injury
that causes the intestine to burst, or an injury to an
internal organ which bleeds into the abdominal cavity.
Symptoms of peritonitis include fever and abdominal pain. An acutely ill patient usually tries to lie very
still, because any amount of movement causes excruciating pain. Often, the patient lies with the knees bent,
to decrease strain on the tender peritoneum. There is
often nausea and vomiting. The usual sounds made by
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Peritonitis

Description

KEY TERMS

Pernicious anemia

KEY TERMS
Ascites—An accumulation of fluid within the
abdominal cavity.
Cirrhosis—A progressive liver disease in which the
liver grows increasingly more scarred. The presence of scar tissue then interferes with liver
function.
Diverticulum—An outpouching of the intestine.
Laparotomy—An open operation on the abdomen.
Pancreatitis—An inflammation of the pancreas.
Perforation—A hole.
Peritoneum—The membrane that lines the inside
of the abdominal cavity, and all of the internal
organs.

the active intestine and heard during examination with
a stethoscope will be absent, because the intestine
usually stops functioning. The abdomen may be rigid
and boardlike. Accumulations of fluid will be notable
in primary peritonitis due to ascites. Other signs and
symptoms of the underlying cause of secondary peritonitis may be present.

performed. Any perforated or damaged organ is
usually repaired at this time. If a clear diagnosis of
pelvic inflammatory disease or pancreatitis can be
made, however, surgery is not usually performed.
Peritonitis from any cause is treated with antibiotics
given through a needle in the vein, along with fluids to
prevent dehydration.

Prognosis
Prognosis for untreated peritonitis is poor,
usually resulting in death. With treatment, the prognosis is variable, dependent on the underlying cause.

Prevention
There is no way to prevent peritonitis, since the
diseases it accompanies are usually not under the
voluntary control of an individual. However, prompt
treatment can prevent complications.
Resources
BOOKS

Isselbacher, Kurt J., and Alan Epstein. ‘‘Diverticular,
Vascular,and Other Disorders of the Intestine and
Peritoneum.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al. New York:
McGraw-Hill,1997.

Rosalyn Carson-DeWitt, MD

Diagnosis
A diagnosis of peritonitis is usually based on
symptoms. Discovering the underlying reason for the
peritonitis, however, may require some work. A blood
sample will be drawn in order to determine the white
blood cell count. Because white blood cells are produced by the body in an effort to combat foreign
invaders, the white blood cell count will be elevated
in the case of an infection. A long, thin needle can be
used to take a sample of fluid from the abdomen in an
effort to diagnose primary peritonitis. The types of
immune cells present are usually characteristic in this
form of peritonitis. X-ray films may be taken if there is
some suspicion that a perforation exists. In the case of
a perforation, air will have escaped into the abdomen
and will be visible on the picture. When a cause for
peritonitis cannot be found, an open exploratory
operation on the abdomen (laparotomy) is considered
to be a crucial diagnostic procedure, and at the same
time provides the opportunity to begin treatment.

Treatment
Treatment depends on the source of the peritonitis, but an emergency laparotomy is usually
2856

Permanent pacemakers see Pacemakers

Pernicious anemia
Definition
Pernicious anemia is a disease in which the red
blood cells are abnormally formed, due to an inability
to absorb vitamin B12. True pernicious anemia refers
specifically to a disorder of atrophied parietal cells
leading to absent intrinsic factor, resulting in an inability to absorb B12.

Description
Vitamin B12, or cobalamin, plays an important
role in the development of red blood cells. It is found
in significant quantities in liver, meats, milk and milk
products, and legumes. During the course of the digestion of foods containing B12, the B12 becomes attached
GALE ENCYCLOPEDIA OF MEDICINE

Pernicious anemia

to a substance called intrinsic factor. Intrinsic factor is
produced by parietal cells that line the stomach. The
B12-intrinsic factor complex then enters the intestine,
where the vitamin is absorbed into the bloodstream. In
fact, B12 can only be absorbed when it is attached to
intrinsic factor.
In pernicious anemia, the parietal cells stop producing intrinsic factor. The intestine is then completely unable to absorb B12. So, the vitamin passes out of
the body as waste. Although the body has significant
amounts of stored B12, this will eventually be used up.
At this point, the symptoms of pernicious anemia will
develop.
Pernicious anemia is most common among people
from northern Europe and among African Americans.
It is far less frequently seen among people from southern Europe and Asia. Pernicious anemia occurs in
equal numbers in both men and women. Most patients
with pernicious anemia are older, usually over 60.
Occasionally, a child will have an inherited condition
that results in defective intrinsic factor. Pernicious
anemia seems to run in families, so that anyone with
a relative diagnosed with the disease has a greater
likelihood of developing it as well.

Causes and symptoms
Intrinsic factor is produced by specialized cells
within the stomach called parietal cells. When these
parietal cells shrink in size (atrophy), they produce less
and less intrinsic factor. Eventually, the parietal cells
stop functioning altogether. Other important products
of parietal cells are also lessened, including stomach
acid, and an enzyme involved in the digestion of
proteins.
People with pernicious anemia seem to have a
greater chance of having certain other conditions.
These conditions include autoimmune disorders, particularly those affecting the thyroid, parathyroid, and
adrenals. It is thought that the immune system,
already out of control in these diseases, incorrectly
becomes directed against the parietal cells.
Ultimately, the parietal cells seem to be destroyed by
the actions of the immune system.
As noted, true pernicious anemia refers specifically to a disorder of atrophied parietal cells leading
to absent intrinsic factor, resulting in an inability to
absorb B12. However, there are other related conditions that result in decreased absorption of B12. These
conditions cause the same types of symptoms as true
pernicious anemia. Other conditions that interfere
with either the production of intrinsic factor, or the
GALE ENCYCLOPEDIA OF MEDICINE

A smear of red blood cells indicating folic acid (vitamin B12)
deficiency. (Custom Medical Stock Photo. Reproduced by
permission.)

body’s use of B12, include conditions that require surgical removal of the stomach, or poisonings with corrosive substances which destroy the lining of the
stomach. Certain structural defects of the intestinal
system can result in an overgrowth of normal bacteria.
These bacteria then absorb B12 themselves, for use in
their own growth. Intestinal worms (especially one
called fish tapeworm) may also use B12, resulting in
anemia. Various conditions that affect the first part of
the intestine (the ileum), from which B12 is absorbed,
can also cause anemia due to B12 deficiency. These
ilium-related disorders include tropical sprue,
Whipple’s disease, Crohn’s disease, tuberculosis, and
the Zollinger-Ellison syndrome.
Symptoms of pernicious anemia and decreased
B12 affect three systems of the body: the system that
is involved in the formation of blood cells (hematopoietic system); the gastrointestinal system; and the
nervous system.
The hematopoietic system is harmed because B12
is required for the proper formation of red blood
cells. Without B12, red blood cell production is
greatly reduced. Those red blood cells that are produced are abnormally large and abnormal in shape.
Because red blood cells are responsible for carrying
oxygen around the body, decreased numbers (termed
anemia) result in a number of symptoms, including
fatigue, dizziness, ringing in the ears, pale or yellowish skin, fast heart rate, enlarged heart with an abnormal heart sound (murmur) evident on examination,
and chest pain.
Symptoms that affect the gastrointestinal system
include a sore and brightly red tongue, loss of appetite,
weight loss, diarrhea, and abdominal cramping.
2857

Pernicious anemia

KEY TERMS
Anemia—A condition in which those elements of
the blood responsible for oxygen delivery throughout the body (red blood cells, hemoglobin) are
decreased in quantity or defective in some way.
Atrophy—Refers to the shrinking in size of an organ
or cell.
Autoimmune disorder—A disorder in which the
immune system, (responsible for fighting off such
foreign invaders as bacteria and viruses), begins to
attack and damage a part of the body as if it were
foreign.
Hematopoietic system—The system in the body
which is responsible for the production of blood cells.
Intrinsic factor—A substance produced by the parietal cells of the stomach. In order to be absorbed
by the intestine, vitamin B12 must form a complex
with intrinsic factor.
Parietal cells—Specific cells which line the inside
of the stomach. These cells are responsible for producing intrinsic factor and hydrochloric acid.
Reticulocyte—An early, immature form of a red
blood cell. Over time, the reticulocyte develops to
become a mature, oxygen-carrying red blood cell.

The nervous system is severely affected when pernicious anemia goes untreated. Symptoms include
numbness, tingling, or burning in the arms, legs,
hands, and feet; muscle weakness; difficulty and loss
of balance while walking; changes in reflexes; irritability, confusion, and depression.

Diagnosis
Diagnosis of pernicious anemia is suggested when
a blood test reveals abnormally large red blood cells.
Many of these will also be abnormally shaped. The
earliest, least mature forms of red blood cells (reticulocytes) will also be low in number. White blood cells
and platelets may also be decreased in number.
Measurements of the quantity of B12 circulating in
the bloodstream will be low.
Once these determinations are made, it will be
important to diagnose the cause of the anemia. True
pernicious anemia means that the parietal cells of the
stomach are atrophied, resulting in decreased production of intrinsic factor. This diagnosis is made by the
Schilling test. In this test, a patient is given radioactive
B12 under two different sets of conditions: once alone,
2858

and once attached to intrinsic factor. Normally, large
amounts of B12 are absorbed through the intestine, then
circulate through the blood, and enter the kidneys,
where a certain amount of B12 is then passed out in the
urine. When a patient has pernicious anemia, the dose of
B12 given by itself will not be absorbed by the intestine, so
it will not pass into the urine. Therefore, levels of B12 in
the urine will be low. When the B12 is given along with
intrinsic factor, the intestine is able to absorb the vitamin. Urine levels of B12 will therefore be higher.

Treatment
Treatment of pernicious anemia requires the
administration of lifelong injections of B12. Vitamin
B12 given by injection enters the bloodstream directly,
and does not require intrinsic factor. At first, injections may need to be given several times a week, in
order to build up adequate stores of the vitamin. After
this, the injections can be given on a monthly basis.
Other substances required for blood cell production
may also need to be given, iron and vitamin C.

Prognosis
Prognosis is generally good for patients with pernicious anemia. Many of the symptoms improve
within just a few days of beginning treatment,
although some of the nervous system symptoms may
take up to 18 months to improve. Occasionally, when
diagnosis and treatment have been delayed for a long
time, some of the nervous system symptoms may be
permanent.
Because an increased risk of stomach cancer has
been noted in patients with pernicious anemia, careful
monitoring is necessary, even when all the symptoms
of the original disorder have improved.
Resources
BOOKS

Babior, Bernard M., and H. Franklin Bunn. ‘‘Megaloblastic
Anemias.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.
PERIODICALS

Toh, Ban-Hock, et al. ‘‘Pernicious Anemia.’’ The New
England Journal of Medicine 337, no. 20 (November 13,
1997): 52+.

Rosalyn Carson-DeWitt, MD

Peroneal muscular atrophy see CharcotMarie-Tooth disease
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Peroxisomal disorders are a group of congenital
(existing from birth) diseases characterized by the
absence of normal peroxisomes in the cells of the
body. Peroxisomes are special parts (organelles) within
a cell that contain enzymes responsible for critical
cellular processes, including oxidation of fatty acids,
biosynthesis of membrane phospholipids (plasmalogens), cholesterol, and bile acids, conversion of amino
acids into glucose, reduction of hydrogen peroxide by
catalase, and prevention of excess synthesis of oxalate
(which can form crystals with calcium, resulting in
kidney stones). Peroxisomal disorders are subdivided
into two major categories. The first are disorders
resulting from a failure to form intact, normal peroxisomes, resulting in multiple metabolic abnormalities,
which are referred to as peroxisome biogenesis disorders (PBD) or as generalized peroxisomal disorders.
The second category includes those disorders resulting
from the deficiency of a single peroxisomal enzyme.
There are about 25 peroxisomal disorders known,
although the number of diseases that are considered
to be separate, distinct peroxisomal disorders varies
among researchers and health care practitioners.

There are many other metabolic deficiencies that
can occur in those who have peroxisomal disorders,
which result in other types of detrimental effects, and
together result in the abnormalities associated with the
peroxisomal disorders. Unfortunately, it is not known
how these abnormalities, and combinations of
abnormalities, cause the disabilities seen in those
afflicted with the disease.
Peroxisomal disorders form a heterogeneous disease group, with different degrees of severity. Included
in the group referred to as PBD are:


Zellweger syndrome (ZS), which is usually fatal
within the first year of life,



neonatal adrenoleukodystrophy (NALD), which is
usually fatal within the first 10 years,



infantile Refsum disease (IRD), which is not as
devastating as ZS and NALD, as the children with
this disorder with time and patience can develop
some degree of motor, cognitive, and communication skills, although death generally occurs during
the second decade of life.



rhizomelic chondrodysplasia punctata (RCDP),
which in its most severe form is fatal within the first
year or two of life. However, survival into the teens
has been known to occur. It is characterized by shortening of the proximal limbs (i.e., the legs from knee
to foot, and the arms from elbow to hand).



Zellweger-like syndrome, which is fatal in infancy,
and is known to be a defect of three particular
enzymes.

Description
A cell can contain several hundred peroxisomes,
which are round or oval bodies with diameters of
about 0.5 micron, that contain proteins that function
as enzymes in metabolic processes. By definition, a
peroxisome must contain catalase, which is an enzyme
that breaks down hydrogen peroxide.
Approximately 50 different biochemical reactions
occur entirely or partially within a peroxisome. Some
of the processes are anabolic, or constructive, resulting
in the synthesis of essential biochemical compounds,
including bile acids, cholesterol, plasmalogens, and
docosahexanoic acid (DHA), which is a long chain
fatty acid that is a component of complex lipids,
including the membranes of the central nervous system. Other reactions are catabolic, or destructive, and
lead to the destruction of some fatty acids, including
very long chain fatty acids (VLCFAs, fatty acids with
more than 22 carbon atoms in their chains), phytanic
acid, pipecolic acid, and the prostoglandins. The peroxisome is involved in breaking down VLCFAs to
lengths that the body can use or get rid of.
When VLCFAs accumulate due to abnormal
functioning of the peroxisomes, they are disruptive
GALE ENCYCLOPEDIA OF MEDICINE

The differences among these disorders are continuous, with overlap between abnormalities. The range
of disease abnormalities may be a result of a corresponding range of peroxisome failure; that is, in severe
cases of ZS, the failure is nearly complete, while in
IRD, there is some degree of peroxisome activity.
In peroxisomal single-enzyme disorders, the peroxisome is intact and functioning, but there is a defect
in only one enzymatic process, with only one corresponding biochemical abnormality. However, these
disorders can be as severe as those in which peroxisomal activity is nearly or completely absent.
2859

Peroxisomal disorders

Peroxisomal disorders

to the structure and stability of certain cells, especially
those associated with the central nervous system and
the myelin sheath, which is the fatty covering of nerve
fibers. The peroxisomal disorders that include effects
on the growth of the myelin sheath are considered to
be part of a group of genetic disorders referred to as
leukodystrophies. While metachromatic leukodystrophy (MLD) usually has its onset in infants or juveniles,
there have been reports of its onset in young adults.

Peroxisomal disorders

X-linked adrenoleukodystrophy (X-ALD) is the
most common of the peroxisomal disorders, affecting
about one in 20,000 males. It is estimated that there are
about 1,400 people in the United States with the disorder. In X–ALD there is a deficiency in the enzyme
that breaks down VLCFAs, which then accumulate in
the myelin and adrenal glands. Onset of X-ALDrelated neurological symptoms occurs at about five–
12 years of age, with death occurring within one to 10
years after onset of symptoms. In addition to physical
abnormalities seen in other types of peroxisomal disorders, common symptoms of X-ALD also include
behavioral changes such as abnormal withdrawal or
aggression, poor memory, dementia, and poor academic performance. Other symptoms are muscle
weakness and difficulties with hearing, speech, and
vision. As the disease progresses, muscle tone deteriorates, swallowing becomes difficult and the patient
becomes comatose. Unless treated with a diet that
includes Lorenzo’s oil, the disease will result in paralysis, hearing loss, blindness, vegetative state, and death.
There are also milder forms of X-ALD: an adult onset
ALD that typically begins between the ages of 21 and
35, and a form that is occasionally seen in women who
are carriers of the disorder. In addition to X-ALD,
there are at least 10 other single-enzyme peroxisomal
disorders, each with its own specific abnormalities.

Causes and symptoms
Most peroxisomal disorders are inherited autosomal recessive diseases, with X-ALD as an exception.
They occur in all countries, among all races and ethnic
groups. They are extremely rare, with frequencies
reported at one in 30,000 to one in 150,000, although
these numbers are only estimates.
In general, developmental delay, mental retardation, and vision and hearing impairment are common
in those who have these disorders. Acquisition of
speech appears to be especially difficult, and because
of the reduced communication abilities, autism is common in those who live longer. Peroxisomal disorder
patients have decreased muscle tone (hypotonia),
which in the most severe cases is generalized, while in
less severe cases, is usually restricted to the neck and
trunk muscles. Sometimes this lack of control is only
noticeable by a curved back in the sitting position.
Head control and independent sitting is delayed, with
most patients unable to walk independently.
Failure to thrive is a common characteristic of
patients with peroxisomal disorder, along with an
enlarged liver, abnormalities in liver enzyme function,
and loss of fats in stools (steatorrhea).
2860

Peroxisomal disorders are also associated with
facial abnormalities, including high forehead, frontal
bossing (swelling), small face, low set ears, and slanted
eyes. These characteristics may not be prominent in
some children, and are especially difficult to identify in
an infant.

Diagnosis
Since hearing and vision deficiencies may be difficult to identify in infants, peroxisomal disorders are
usually detected by observations of failure to thrive,
hypotonia, mental retardation, widely open fontanel,
abnormalities in liver enzymes, and an enlarged liver.
If peroxisomal disorders are suspected, blood plasma
assays for VLCFAs, phytanic acid, and pipecolic acid
are conducted. Additional tests include plasmalogen
biosynthesis potential.

Treatment
For many of the peroxisomal disorders, there is no
standard course of treatment, with supportive treatment strategies focusing on alleviation of complications and symptoms. In general, most treatments that
are attempted are dietary, whereby attempts are made
to artificially correct biochemical abnormalities associated with the disorders. Therapies include supplementation of the diet with antioxidant vitamins, or
limitation of intake of fatty acids, especially VLCFAs.
Another area of dietary therapy that is being
investigated is the supplementation of the diet with
pure DHA, given as early in life as possible, in conjunction with a normal well-balanced diet. Some
results have indicated that if given soon enough during
development, DHA therapy may prevent some of the
devastating consequences of peroxisomal disorders,
including brain damage and the loss of vision.
Other treatment strategies include addition of
important missing chemicals. For example, in disorders where there is faulty adrenal function, replacement adrenal hormone therapy is used.
Any dietary changes should be monitored biochemically to determine if the supplements are having
their desired effects and are not causing additional
adverse effects.
Bone marrow transplants may be used to treat
X-ALD, and can be effective if done early in the course
of the childhood form of the disease.
Physical and psychological therapies are important for all types of peroxisomal disorders.
GALE ENCYCLOPEDIA OF MEDICINE

Autosomal recessive inheritance—Two copies of
an altered gene located on one of the autosomes
must be present for an individual to be affected with
the trait or condition determined by that gene:


an affected individual (homozygote) has two parents who are unaffected but each parent carries
the altered gene (heterozygote).



the risk of two heterozygotes, or carriers, having
an affected child is 25%, one in four, for each child
that they have; similarly, there is a three in four
chance that each child will not be affected.



males and females are at equal risk for being
affected.



two affected individuals usually produce children,
all of whom are affected as well.

Autosome—A chromosome not involved in sex
determination.
Fontanel—One of the membranous intervals
between the uncompleted angles of the parietal
and neighboring bones of a fetal or young skull;
so called because it exhibits a rhythmical pulsation.
Metabolic—Relating to the chemical changes in
living cells.
Organelle—Specialized structure within a cell,
which is separated from the rest of the cell by a
membrane composed of lipids and proteins, where
chemical and metabolic functions take place.

Alternative treatment
Patients with peroxisomal disorders, and particularly X-ALD, have been treated with a mixture
of glycerol trioleate-glycerol trieucate (4:1 by
volume), prepared from olive and rapeseed oils,
and referred to as Lorenzo’s oil (developed by
parents of a son, Lorenzo, who had X-ALD,
whose story was documented in the 1992 movie,
Lorenzo’s Oil), to decrease the levels of VLCFA.
Other diets that have been tried include dietary
supplementation with plasmalogen precursors to
increase plasmalogen levels and with cholic acid
to normalize bile acids. However, there has been
only limited success demonstrated with the use of
these treatments. More research is needed to determine the long-term safety and effectiveness of these
treatment strategies.
GALE ENCYCLOPEDIA OF MEDICINE

Peroxisomal disorders range from life-threatening
to cases in which people may function with some
degree of mental and motor retardation. As of 2001,
there was not yet a cure. Enzyme replacement therapies, including enzyme infusion, transplantation, and
gene therapy, may hold promise for future advances in
the treatment of these disorders. Research is being
conducted to increase scientific understanding of
these disorders and to find ways to prevent, treat,
and cure them.

Prevention
Unfortunately not enough is yet known about
these diseases to develop comprehensive strategies
for prevention. Genetic counseling is recommended
for known or suspected carriers. As genes are identified that result in the disorders, genetic testing is being
developed to identify carriers, who then can manage
their reproduction to avoid the possibility of children
being born with these deficiencies. As the genetic bases
for the disorders are defined, prenatal diagnosis and
identification of carriers will be facilitated. For example, for X-ALD, diagnosis can be made from cultured
skin fibroblasts or amniotic fluid cells. This allows
prenatal diagnosis and carrier identification in 90%
of those affected. More recently it has been shown that
biochemical diagnosis can be performed through
chorionic villi biopsy, a procedure performed very
early in the first trimester of pregnancy.
Animal models of ZS and X-ADL have been
developed and are providing researchers with methods
to define pathogenic mechanisms and to evaluate new
therapies.
Resources
PERIODICALS

Gallo, S., et al. ‘‘Late Onset MLD With Normal Nerve
Conduction Associated With Two Novel Missense
Mutations in the ASA Gene.’’ Journal of Neurology,
Neurosurgery, and Psychiatry April 2004: 655–658.
Martinez, Manuela. ‘‘The Fundamental and Practice of
Docosahexanoic Acid Therapy in Peroxisomal
Disorders.’’ Current Opinion in Clinical Nutrition and
Metabolic Care 3 (2000): 101–108.
Martinez, M., E. Vazquez, M. T. Garcia Silva, J. Manzanares,
J. M. Bertran, F. Castello, and I. Mougan. ‘‘Therapeutic
Effects of Docosahexanoic Acid in Patients with
Generalized Peroxisomal Disorders.’’ American Journal
of Clinical Nutrition 71 (2000): 376s–385s.
Moser, Hugo W. ‘‘Molecular Genetics of Peroxisomal
Disorders.’’ Frontiers in Bioscience 5 (March 1, 2001):
298–306.
2861

Peroxisomal disorders

Prognosis

KEY TERMS

Personality disorders

Raymond, G. V. ‘‘Peroxisomal Disorders.’’ Current Opinion
in Pediatrics 11 (December 1999): 572–576.
ORGANIZATIONS

National Institute of Neurological Disorders and Stroke,
NIH Neurological Institute. P.O. Box 5801 Bethesda,
MD 20824. (800) 352-9424. <http://www.ninds.nih.gov/index.htm>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812- 8923.
OTHER

The Peroxisome Website. <http://www.peroxisome.org>.

Judith Sims
Teresa G. Odle

Persantine-thallium heart scan see Thallium
heart scan

Personality disorders
Definition
Personality disorders are a group of mental disturbances defined by the fourth edition, text revision (2000)
of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV) as ‘‘enduring pattern[s] of inner
experience and behavior’’ that are sufficiently rigid and
deep-seated to bring a person into repeated conflicts
with his or her social and occupational environment.
DSM-IV specifies that these dysfunctional patterns
must be regarded as nonconforming or deviant by the
person’s culture, and cause significant emotional pain
and/or difficulties in relationships and occupational performance. In addition, the patient usually sees the
disorder as being consistent with his or her self-image
(ego-syntonic) and may blame others for his or her
social, educational, or work-related problems.

Description
To meet the diagnosis of personality disorder,
which is sometimes called character disorder, the
patient’s problematic behaviors must appear in two
or more of the following areas:


perception and interpretation of the self and other
people



intensity and duration of feelings and their appropriateness to situations



relationships with others



ability to control impulses

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Personality disorders have their onset in late adolescence or early adulthood. Doctors rarely give a
diagnosis of personality disorder to children on the
grounds that children’s personalities are still in the
process of formation and may change considerably
by the time they are in their late teens. In retrospect,
however, many individuals with personality disorders
could be judged to have shown evidence of the problems in childhood.
It is difficult to give close estimates of the percentage of the population that has personality disorders.
Patients with certain personality disorders, including
antisocial and borderline disorders, are more likely to
get into trouble with the law or otherwise attract
attention than are patients whose disorders chiefly
affect their capacity for intimacy. On the other hand,
some patients, such as those with narcissistic or obsessive-compulsive personality disorders, may be outwardly successful because their symptoms are useful
within their particular occupations. It has, however,
been estimated that about 15% of the general population of the United States has a personality disorder,
with higher rates in poor or troubled neighborhoods.
The rate of personality disorders among patients in
psychiatric treatment is between 30% and 50%. It is
possible for patients to have a so-called dual diagnosis;
for example, they may have more than one personality
disorder, or a personality disorder together with a
substance-abuse problem.
By contrast, DSM-IV classifies personality disorders into three clusters based on symptom similarities:


Cluster A (paranoid, schizoid, schizotypal): Patients
appear odd or eccentric to others.



Cluster B (antisocial, borderline, histrionic, narcissistic): Patients appear overly emotional, unstable, or
self-dramatizing to others.



Cluster C (avoidant, dependent, obsessive-compulsive): Patients appear tense and anxiety-ridden to
others.

The DSM-IV clustering system does not mean
that all patients can be fitted neatly into one of the
three clusters. It is possible for patients to have symptoms of more than one personality disorder or to have
symptoms from different clusters.
Some psychiatrists maintain that the DSM-IV
classification is inadequate and should be expanded
to include three additional categories: passive-aggressive personality disorder, characterized by a need to
control or punish others through frustrating them or
sabotaging plans; cyclothymic personality disorder,
characterized by intense mood swings alternating
GALE ENCYCLOPEDIA OF MEDICINE

Since the criteria for personality disorders include
friction or conflict between the patient and his or her
social environment, these syndromes are open to redefinition as societies change. Successive editions of
DSM have tried to be sensitive to cultural differences,
including changes over time, when defining personality disorders. One category that had been proposed for
DSM-III-R, self-defeating personality disorder, was
excluded from DSM-IV on the grounds that its definition reflected prejudice against women. DSM-IV
recommends that doctors take a patient’s background,
especially recent immigration, into account before
deciding that he or she has a personality disorder.
One criticism that has been made of the general category of personality disorder is that it is based on
Western notions of individual uniqueness. Its applicability to people from cultures with different definitions of human personhood is thus open to question.
Furthermore, even within a culture, it can be difficult
to define the limits of ‘‘normalcy.’’
The personality disorders defined by DSM-IV are
as follows:
Paranoid
Patients with paranoid personality disorder are
characterized by suspiciousness and a belief that others
are out to harm or cheat them. They have problems
with intimacy and may join cults or groups with paranoid belief systems. Some are litigious, bringing lawsuits against those they believe have wronged them.
Although not ordinarily delusional, these patients
may develop psychotic symptoms under severe stress.
It is estimated that 0.5–2.5% of the general population
meet the criteria for paranoid personality disorder.
Schizoid
Schizoid patients are perceived by others as
‘‘loners’’ without close family relationships or social
contacts. Indeed, they are aloof and really do prefer to
be alone. They may appear cold to others because they
rarely display strong emotions. They may, however, be
successful in occupations that do not require personal
interaction. About 2% of the general population has
this disorder. It is slightly more common in men than
in women.
Schizotypal
Patients diagnosed as schizotypal are often
considered odd or eccentric because they pay little
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attention to their clothing and sometimes have
peculiar speech mannerisms. They are socially isolated and uncomfortable in parties or other social
gatherings. In addition, people with schizotypal
personality disorder often have oddities of thought,
including ‘‘magical’’ beliefs or peculiar ideas (for
example, a belief in telepathy or UFOs) that are
outside of their cultural norms. It is thought that
3% of the general population has schizotypal personality disorder. It is slightly more common in
males. Schizotypal disorder should not be confused
with schizophrenia, although there is some evidence
that the disorders are genetically related.
Antisocial
Patients with antisocial personality disorder are
sometimes referred to as sociopaths or psychopaths.
They are characterized by lying, manipulativeness,
and a selfish disregard for the rights of others; some
may act impulsively. People with antisocial personality disorder are frequently chemically dependent and
sexually promiscuous. It is estimated that 3% of males
in the general population and 1% of females have
antisocial personality disorder.
Borderline
Patients with borderline personality disorder
(BPD) are highly unstable, with wide mood swings, a
history of intense but stormy relationships, impulsive
behavior, and confusion about career goals, personal
values, or sexual orientation. These often highly conflictual ideas may correspond to an even deeper confusion about their sense of self (identity). People with
BPD frequently cut or burn themselves, or threaten or
attempt suicide. Many of these patients have histories
of severe childhood abuse or neglect. About 2% of the
general population have BPD; 75% of these patients
are female.
Histrionic
Patients diagnosed with this disorder impress
others as overly emotional, overly dramatic, and hungry for attention. They may be flirtatious or seductive
as a way of drawing attention to themselves, yet they
are emotionally shallow. Histrionic patients often live
in a romantic fantasy world and are easily bored with
routine. About 2–3% of the population is thought to
have this disorder. Although historically the disorder
has been more associated with womenin clinical settings, there may be bias toward diagnosing women
with the histrionic personality disorder.
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Personality disorders

between high spirits and moroseness or gloom; and
depressive personality disorder, characterized by a
negative and pessimistic approach to life.

Personality disorders

Narcissistic
Narcissistic patients are characterized by selfimportance, a craving for admiration, and exploitative
attitudes toward others. They have unrealistically
inflated views of their talents and accomplishments,
and may become extremely angry if they are criticized
or outshone by others. Narcissists may be professionally
successful but rarely have long-lasting intimate relationships. Fewer than 1% of the population has this disorder; about 75% of those diagnosed with it are male.
Avoidant
Patients with avoidant personality disorder are fearful of rejection and shy away from situations or occupations that might expose their supposed inadequacy. They
may reject opportunities to develop close relationships
because of their fears of criticism or humiliation. Patients
with this personality disorder are often diagnosed with
dependent personality disorder as well. Many also fit the
criteria for social phobia. Between 0.5–1.0% of the
population have avoidant personality disorder.
Dependent
Dependent patients are afraid of being on their
own and typically develop submissive or compliant
behaviors in order to avoid displeasing people. They
are afraid to question authority and often ask others
for guidance or direction. Dependent personality disorder is diagnosed more often in women, but it has
been suggested that this finding reflects social pressures on women to conform to gender stereotyping or
bias on the part of clinicians.
Obsessive-compulsive
Patients diagnosed with this disorder are preoccupied with keeping order, attaining perfection, and
maintaining mental and interpersonal control. They
may spend a great deal of time adhering to plans,
schedules, or rules from which they will not deviate,
even at the expense of openness, flexibility, and efficiency. These patients are often unable to relax and
may become ‘‘workaholics.’’ They may have problems
in employment as well as in intimate relationships
because they are very stiff and formal, and insist on
doing everything their way. About 1% of the population has obsessive-compulsive personality disorder;
the male/female ratio is about 2:1.

Causes and symptoms
Personality disorders are thought to result from a
bad interface, so to speak, between a child’s
2864

temperament and character on one hand and his or
her family environment on the other. Temperament
can be defined as a person’s innate or biologically
shaped basic disposition. Human infants vary in
their sensitivity to light or noise, their level of physical
activity, their adaptability to schedules, and similar
traits. Even such traits as shyness or novelty-seeking
may be at least in part determined by the biology of the
brain and the genes one inherits.
Character is defined as the set of attitudes and
behavior patterns that the individual acquires or learns
over time. It includes such personal qualities as work
and study habits, moral convictions, neatness or cleanliness, and consideration of others. Since children must
learn to adapt to their specific families, they may
develop personality disorders in the course of struggling
to survive psychologically in disturbed or stressful
families. For example, nervous or high-strung parents
might be unhappy with a baby who is very active and
try to restrain him or her at every opportunity. The
child might then develop an avoidant personality disorder as the outcome of coping with constant frustration and parental disapproval. As another example,
child abuse is believed to play a role in shaping borderline personality disorder. One reason that some therapists use the term developmental damage instead of
personality disorder is that it takes the presumed source
of the person’s problems into account.
Some patients with personality disorders come
from families that appear to be stable and healthy. It
has been suggested that these patients are biologically
hypersensitive to normal family stress levels. Levels of
the brain chemical (neurotransmitter) dopamine may
influence a person’s level of novelty-seeking, and serotonin levels may influence aggression.
Other factors that have been cited as affecting children’s personality development are the mass media and
social or group hysteria, particularly after the events of
September 11, 2001. Cases of so-called mass sociogenic
illness have been identified, in which a group of children
began to vomit or have other physical symptoms
brought on in response to an imaginary threat. In two
such cases, the children were reacting to the suggestion
that toxic fumes were spreading through their school.
Some authors believe that overly frequent or age-inappropriate discussions of terrorist attacks or bioterrorism
may make children more susceptible to sociogenic illness
as well as other distortions of personality.

Diagnosis
Diagnosis of personality disorders is complicated
by the fact that affected persons rarely seek help until
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There are no tests that can provide a definitive
diagnosis of personality disorder. Most doctors will
evaluate a patient on the basis of several sources of
information collected over a period of time in order to
determine how long the patient has been having difficulties, how many areas of life are affected, and how
severe the dysfunction is. These sources of information
may include:
Interviews
The doctor may schedule two or three interviews
with the patient, spaced over several weeks or months,
in order to rule out an adjustment disorder caused by
job loss, bereavement, or a similar problem. An office
interview allows the doctor to form an impression of
the patient’s overall personality as well as obtain information about his or her occupation and family.
During the interview, the doctor will note the patient’s
appearance, tone of voice, body language, eye contact,
and other important non-verbal signals, as well as the
content of the conversation. In some cases, the doctor
may contact other people (family members, employers, close friends) who know the patient well in order
to assess the accuracy of the patient’s perception of his
or her difficulties. It is quite common for people with
personality disorders to have distorted views of their
situations or to be unaware of the impact of their
behavior on others.

specialized training. Doctors usually refer patients to
a clinical psychologist for this type of test.
PERSONALITY INVENTORIES. Personality inventories are tests with true/false or yes/no answers that
can be used to compare the patient’s scores with those
of people with known personality distortions. The
single most commonly used test of this type is the
Minnesota Multiphasic Personality Inventory, or
MMPI. Another test that is often used is the Millon
Clinical Multiaxial Inventory, or MCMI.
PROJECTIVE TESTS. Projective tests are unstructured. Unstructured means that instead of giving oneword answers to questions, the patient is asked to talk at
some length about a picture that the psychologist has
shown him or her, or to supply an ending for the beginning of a story. Projective tests allow the clinician to
assess the patient’s patterns of thinking, fantasies, worries or anxieties, moral concerns, values, and habits.
Common projective tests include the Rorschach, in
which the patient responds to a set of ten inkblots;
and the Thematic Apperception Test (TAT), in which
the patient is shown drawings of people in different
situations and then tells a story about the picture.

Treatment
At one time psychiatrists thought that personality
disorders did not respond very well to treatment. This
opinion was derived from the notion that human personality is fixed for life once it has been molded in
childhood, and from the belief among people with
personality disorders that their own views and behaviors are correct, and that others are the ones at fault.
More recently, however, doctors have recognized that
humans can continue to grow and change throughout
life. Most patients with personality disorders are now
considered to be treatable, although the degree of
improvement may vary. The type of treatment recommended depends on the personality characteristics
associated with the specific disorder.
Hospitalization
Inpatient treatment is rarely required for patients
with personality disorders, with two major exceptions:
borderline patients who are threatening suicide or
suffering from drug or alcohol withdrawal; and
patients with paranoid personality disorder who are
having psychotic symptoms.

Psychologic testing
Doctors use psychologic testing to help in the
diagnosis of a personality disorder. Most of these
tests require interpretation by a professional with
GALE ENCYCLOPEDIA OF MEDICINE

Psychotherapy
Psychoanalytic psychotherapy is suggested for
patients who can benefit from insight-oriented
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Personality disorders

they are in serious trouble or until their families (or the
law) pressure them to get treatment. The reason for
this slowness is that the problematic traits are so deeply entrenched that they seem normal (ego-syntonic)
to the patient. Diagnosis of a personality disorder
depends in part on the patient’s age. Although personality disorders originate during the childhood years,
they are considered adult disorders. Some patients, in
fact, are not diagnosed until late in life because their
symptoms had been modified by the demands of their
job or by marriage. After retirement or the spouse’s
death, however, these patients’ personality disorders
become fully apparent. In general, however, if the
onset of the patient’s problem is in mid- or late-life,
the doctor will rule out substance abuse or personality
change caused by medical or neurological problems
before considering the diagnosis of a personality disorder. It is unusual for people to develop personality
disorders ‘‘out of the blue’’ in mid-life.

Personality disorders

treatment. These patients typically include those with
dependent, obsessive-compulsive, and avoidant personality disorders. Doctors usually recommend individual psychotherapy for narcissistic and borderline
patients, but often refer these patients to therapists
with specialized training in these disorders.
Psychotherapeutic treatment for personality disorders
may take as long as three to five years.
Insight-oriented approaches are not recommended for patients with paranoid or antisocial personality disorders. These patients are likely to resent
the therapist and see him or her as trying to control or
dominate them.
Supportive therapy is regarded as the most helpful
form of psychotherapy for patients with schizoid personality disorder.
Cognitive-behavioral therapy
Cognitive-behavioral approaches are often
recommended for patients with avoidant or dependent
personality disorders. Patients in these groups typically have mistaken beliefs about their competence or
likableness. These assumptions can be successfully
challenged by cognitive-behavioral methods. More
recently, Aaron Beck and his coworkers have successfully extended their approach to cognitive therapy to
all ten personality disorders as defined by DSM-IV.
Group therapy
Group therapy is frequently useful for patients with
schizoid or avoidant personality disorders because it
helps them to break out of their social isolation. It has
also been recommended for patients with histrionic and
antisocial personality disorders. These patients tend to
act out, and pressure from peers in group treatment can
motivate them to change. Because patients with antisocial personality disorder can destabilize groups that
include people with other disorders, it is usually best if
these people meet exclusively with others who have
APD (in homogeneous groups).
Family therapy
Family therapy may be suggested for patients
whose personality disorders cause serious problems
for members of their families. It is also sometimes
recommended for borderline patients from overinvolved or possessive families.
Medications
Medications may be prescribed for patients with
specific personality disorders. The type of medication
2866

depends on the disorder. In general, however, patients
with personality disorders are helped only moderately
by medications.
ANTIPSYCHOTIC DRUGS. Antipsychotic drugs, such
as haloperidol (Haldol), may be given to patients with
paranoid personality disorder if they are having brief
psychotic episodes. Patients with borderline or schizotypal personality disorder are sometimes given antipsychotic drugs in low doses; however, the efficacy of
these drugs in treating personality disorder is less clear
than in schizophrenia.
MOOD STABILIZERS. Carbamazepine (Tegretol) is
a drug that is commonly used to treat seizures, but is
also helpful for borderline patients with rage outbursts
and similar behavioral problems. Lithium and valproate may also be used as mood stabilizers, especially
among people with borderline personality disorder.
ANTIDEPRESSANTS AND ANTI-ANXIETY MEDICATIONS. Medications in these categories are sometimes

prescribed for patients with schizoid personality disorder to help them manage anxiety symptoms while
they are in psychotherapy. Antidepressants are also
commonly used to treat people with borderline personality disorder.
Treatment with medications is not recommended
for patients with avoidant, histrionic, dependent, or
narcissistic personality disorders. The use of potentially
addictive medications should be avoided in people with
borderline or antisocial personality disorders. However,
some avoidant patients who also have social phobia may
benefit from monoamine oxidase inhibitors (MAO inhibitors), a particular class of antidepressant.

Prognosis
The prognosis for recovery depends in part on the
specific disorder. Although some patients improve as
they grow older and have positive experiences in life,
personality disorders are generally life-long disturbances with periods of worsening (exacerbations)
and periods of improvement (remissions). Others, particularly schizoid patients, have better prognoses if
they are given appropriate treatment. Beck and his
coworkers estimate that effective cognitive therapy
with patients with personality disorders takes two to
three years on average. Patients with paranoid personality disorder are at some risk for developing delusional disorders or schizophrenia.
The personality disorders with the poorest prognoses are the antisocial and the borderline. Borderline
patients are at high risk for developing substance
abuse disorders or bulimia. About 80% of
GALE ENCYCLOPEDIA OF MEDICINE

Character—An individual’s set of emotional, cognitive, and behavioral patterns learned and accumulated over time.
Character disorder—Another name for personality
disorder.
Cognitive therapy—A form of psychotherapy that
focuses on changing people’s patterns of emotional
reaction by correcting distorted patterns of thinking
and perception.
Developmental damage—A term that some therapists prefer to personality disorder, on the grounds
that it is more respectful of the patient’s capacity for
growth and change.
Ego-syntonic—Consistent with one’s sense of self,
as opposed to ego-alien or dystonic (foreign to
one’s sense of self). Ego-syntonic traits typify
patients with personality disorders.
Neuroleptic—Another name for older antipsychotic medications, such as haloperidol. The term does
not apply to such newer atypical agents as clozapine (Clozaril).
Personality—The organized pattern of behaviors
and attitudes that makes a human being distinctive.
Personality is formed by the ongoing interaction of
temperament, character, and environment.
Projective tests—Psychological tests that probe
into personality by obtaining open-ended
responses to such materials as pictures or stories.
Projective tests are often used to evaluate patients
with personality disorders.
Rorschach test—A well-known projective test that
requires the patient to describe what he or she sees
in each of 10 inkblots. It is named for the Swiss
psychiatrist who invented it.
Temperament—A person’s natural or genetically
determined disposition.

hospitalized borderline patients attempt suicide at
some point during treatment, and about 5% succeed
in committing suicide. Borderline patients are also the
most likely to sue their mental health professional for
malpractice.

Prevention
The most effective preventive strategy for personality disorders is early identification and treatment of
GALE ENCYCLOPEDIA OF MEDICINE

children at risk. High-risk groups include abused children, children from troubled families, children with
close relatives diagnosed with personality disorders,
children of substance abusers, and children who
grow up in cults or extremist political groups.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, D.C.: American Psychiatric Association,
2000.
Beck, Aaron T., Arthur Freeman, Denise D. Davis, et al.
Cognitive Therapy of Personality Disorders. 2nd ed.
New York: The Guilford Press, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Personality Disorders.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Battle, C. L., M. T. Shea, D. M. Johnson, et al. ‘‘Childhood
Maltreatment Associated with Adult Personality
Disorders: Findings from the Collaborative
Longitudinal Personality Disorders Study.’’ Journal of
Personality Disorders 18 (April 2004): 193–211.
Bienenfeld, David, MD. ‘‘Personality Disorders.’’ eMedicine
August 18, 2004. <http://www.emedicine.com/med/
topic3472.htm>.
Doyle, C. R., J. Akhtar, R. Mrvos, and E. P. Krenzelok.
‘‘Mass Sociogenic Illness—Real and Imaginary.’’
Veterinary and Human Toxicology 46 (April 2004):
93–95.
Gutheil, T. G. ‘‘Suicide, Suicide Litigation, and Borderline
Personality Disorder.’’ Journal of Personality Disorders
18 (June 2004): 248–256.
Jordan, A. ‘‘The Role of Media in Children’s Development:
An Ecological Perspective.’’ Journal of Developmental
and Behavioral Pediatrics 25 (June 2004): 196–206.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry
(AACAP). 3615 Wisconsin Avenue, NW, Washington,
DC 20016-3007. (202) 966-7300. Fax: (202) 966-2891.
<http://www.aacap.org>.
American Psychiatric Association (APA). 1400 K Street,
NW, Washington, DC 20005. <http://
www.psych.org>.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513. <http://
www.nimh.nih.gov>.

Rebecca J. Frey, PhD

Perthes disease see Osteochondroses
Pertussis see Whooping cough
2867

Personality disorders

KEY TERMS

Pervasive developmental disorders

Pervasive developmental
disorders
Definition
Pervasive developmental disorders include five
different conditions: Asperger’s syndrome, autistic
disorder, childhood disintegrative disorder (CDD),
pervasive developmental disorder not otherwise specified (PDDNOS), and Rett’s syndrome. They are
grouped together because of the similarities between
them. The three most common shared problems
involve communication skills, motor skills, and social
skills. Since there are no clear diagnostic boundaries
separating these conditions it is sometimes difficult to
distinguish one from the other for diagnostic
purposes.
Asperger’s syndrome, autistic disorder, and childhood disintegrative disorder are four to five times
more common in boys, and Rett’s syndrome has
been diagnosed primarily in girls. All of these disorders are rare.

Description
Asperger’s syndrome
Children afflicted with Asperger’s syndrome exhibit difficulties in social relationships and communication. They are reluctant to make eye contact, do not
respond to social or emotional contacts, do not initiate
play activities with peers, and do not give or receive
attention or affection. To receive this diagnosis the
individual must demonstrate normal development of
language, thinking and coping skills. Due to an
impaired coordination of muscle movements, they
appear to be clumsy. They usually become deeply
involved in very few interests, which tend to occupy
most of their time and attention.
Autistic disorder
Autistic disorder is frequently evident within the
first year of life, and must be diagnosed before age
three. It is associated with moderate mental retardation in three out of four cases. These children do not
want to be held, rocked, cuddled or played with. They
are unresponsive to affection, show no interest in peers
or adults and have few interests. Other traits include
avoidance of eye contact, an expressionless face and
the use of gestures to express needs. Their actions are
repetitive, routine and restricted. Rocking, hand and
arm flapping, unusual hand and finger movements,
and attachment to objects rather than pets and people
2868

are common. Speech, play, and other behaviors are
repetitive and without imagination. They tend to be
overactive, aggressive, and self-injurious. They are
often highly sensitive to touch, noise, and smells and
do not like changes in routine. Autism and several
disorders classified with it have increased significantly
in recent years so that they now are diagnosed more
often in children than spina bifida, cancer, or Down
syndrome. This may be due partly to improved recognition and diagnosis.
Childhood disintegrative disorder
Childhood disintegrative disorder is also called
Heller’s disease and most often develops between two
and ten years of age. Children with CDD develop
normally until two to three years of age and then
begin to disintegrate rapidly. Signs and symptoms
include deterioration of the ability to use and understand language to the point where they are unable to
carry on a conversation. This is accompanied by loss
of control of the bladder and bowels. Any interest or
ability to play and engage in social activities is lost.
The behaviors are nearly identical with those that are
characteristic of autistic disorder. However, childhood
disintegrative disorder becomes evident later in life
and results in developmental regression, or loss of
previously attained skills, whereas autistic disorder
can be detected as early as the first month of life and
results in a failure to progress.
Pervasive developmental disorder not otherwise
specified
The term pervasive developmental disorder not
otherwise specified (PDDNOS) is also referred to as
atypical personality development, atypical PDD, or
atypical autism. Individuals with this disorder share
some of the same signs and symptoms of autism or
other conditions under the category of pervasive
developmental disorders, but do not meet all of the
criteria for diagnosis for any of the four syndromes
included in this group of diseases. Because the children
diagnosed with PDDNOS do not all exhibit the same
combination of characteristics, it is difficult to do
research on this disorder, but the limited evidence
available suggests that patients are seen by medical
professionals later in life than is the case for autistic
children, and they are less likely to have intellectual
deficits.
Rett’s syndrome
Rett’s syndrome was first described in 1966 and is
found almost exclusively in girls. It is a disease in
GALE ENCYCLOPEDIA OF MEDICINE

The course of the illness has been divided into four
stages. In stage one the child develops normally for six
to 18 months. In stage two, development slows down
and stops. Stage three is characterized by a loss of the
speech and motor skills already acquired. Typically
this happens between nine months and three years of
age. Stage four begins with a return to learning that
will continue across the lifespan, but at a very slow
rate. Problems with coordination and walking are
likely to continue and even worsen. Other conditions
that can occur with Rett’s syndrome are convulsions,
constipation, breathing problems, impaired circulation
in the feet and legs, and difficulty chewing or
swallowing.

Autism:


all listed for PDDNOS



severe impairment in communication



abnormal social interaction and use of language for
social communication or imaginative play before age
of three



not better accounted for by another psychiatric order
Asperger’s disorder:



all listed for PDDNOS



clinically significant impairment in social, occupational, or other areas of functioning



no general delay in language



no delay in cognitive development, self-help skills, or
adaptive behavior



not better accounted for by another pervasive developmental disorder or schizophrenia
Rett’s syndrome:



a period of normal development between 6–18
months



normal head circumference at birth, followed by a
slowing of head growth



retardation



repetitive hand movements

Causes and symptoms
The causes of these disorders are unknown
although brain structure abnormalities, genetic mutation, and alterations in brain function are believed to
play a role. Still, no single brain abnormality or location has been connected to a cause. In 2004, scientists
reported finding the gene mutation (on gene MECP2)
that is present in 80% of people affected with Rett’s
syndrome. In 2004, comprehensive review of research
on twins revealed that interactions between multiple
genes may play a role in the cause of autism. A number
of neurological conditions, such as convulsions, are
commonly found to accompany these disorders.

Diagnosis
The diagnosis of pervasive developmental disorder is made by medical specialists based on a thorough
examination of the patient, including observing behavior and gathering information from parents and caregivers. Because many symptoms are common to more
than one condition, distinctions between conditions
must be carefully made. The following summary
describes the distinction between three common
disorders.
PDDNOS:


impairment of two-way social interaction



Repetitive and predictable behavior patterns and
activities

GALE ENCYCLOPEDIA OF MEDICINE

CDD:


normal development for at least two years



loss of skills in at least two of the following areas:
language, social skills, bowel or bladder control,
play, movement skills



abnormal functioning in at least two of the following
areas: social interaction, communication, behavior
patterns



not better accounted for by another PDD or mental
illness

Treatment
Treatment for children with pervasive developmental disorders is limited. Those who can be enrolled
in educational programs will need a highly structured
learning environment, a teacher-student ratio of not
more than 1:2, and a high level of parental involvement that provides consistent care at home.
Psychotherapy and social skills training can prove
helpful to some. There is no specific medication available for treating the core symptoms of any of these
disorders, though research is promising. Some psychiatric medications may be helpful in controlling
2869

Pervasive developmental disorders

which cells in the brain experience difficulty in communicating with each other. At the same time the
growth of the head falls behind the growth of the
body so that these children are usually mentally
retarded. These conditions are accompanied by deficits in movement (motor) skills and a loss of interest in
social activities.

Pet therapy

KEY TERMS
Hydrotherapy—This term literally means ‘‘water
treatment’’ and involves the use of water in physical therapy as well as treatment of physical and
emotional illness.
Mutation—A mutation is a change in a gene. Since
genes determine how a body is structured and
functions, any change in a gene will produce
some change in these areas.
Neurological conditions—A condition that has its
origin in some part of the patient’s nervous system.

particular behavior difficulties, such as agitation,
mood instability, and self-injury. Music, massage,
and hydrotherapy may exert a calming effect on behavior. Treatment may also include physical and occupational therapy.

Prognosis
In general, the prognosis in all of these conditions
is tied to the severity of the illness.
The prognosis for Asperger’s syndrome is more
hopeful than that for other diseases in this cluster.
These children are likely to grow up to be functional
independent adults, but will always have problems
with social relationships. They are also at greater risk
for developing serious mental illness than the general
population.
The prognosis for autistic disorder is not as good,
although great strides have been made in recent years
in its treatment. The higher the patient’s IQ (intelligence quotient) and ability to communicate, the better
the prognosis. However, many patients will always
need some level of custodial care. In the past, most of
these individuals were confined to institutions, but
many are now able to live in group homes or supervised apartments. The prognosis for childhood disintegrative disorder is even less favorable. These
children will require intensive and long-term care.
Children diagnosed with PDDNOS have a better
prognosis because their initial symptoms are usually
milder, IQ scores are higher, and language development is stronger.

Prevention
The causes of pervasive developmental disorders
are not understood, although research efforts are
2870

getting closer to understanding the problem. Until
the causes are discovered, it will remain impossible to
prevent these conditions.
Resources
PERIODICALS

‘‘MECP2 Open Reading Framd Defines Protein Linked to
Rett Syndrome.’’ Biotech Week June 9, 2004: 300.
Muhle, Rebecca, Stephanie V. Trentacoste, and Isabelle
Rapin. ‘‘The Genetics of Autism.’’ Pediatrics May 2004:
1389–1391.
ORGANIZATIONS

Autism Society of America. 7910 Woodmont Avenue, Suite
300, Bethesda, Maryland 20814-3067. (800) 328-8476.
<http://www.autism-society.org>.
International Rett Syndrome Association. 9121 Piscataway
Road, Suite 2B, Clinton, MD 20735. (800) 818-7388.
<http://www.rettsyndrome.org>.
Learning Disabilities Association of America. 4156 Library
Road, Pittsburg, PA 15234. (412) 341-1515. <http://
www.ldanatl.org>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.
OTHER

Boyle, Thomas D. ‘‘Diagnosing Autism and Other Pervasive
Personality Disorders.’’ INJersye.com Page. <http://
www.injersey.com>.
‘‘Childhood Disintegrative Disorder.’’ HealthAnswers.com.
<http://www.healthanswers.com/database/ami/converted/001535.html>.
‘‘Information on Childhood Disintegrative Disorder.’’ YaleNew Haven Medical Center Page. <http://
info.med.yale.edu>.
The International Rett Syndrome Association. 9121
Piscataway Road, Suite 2B, Clinton, MD 20735. (800)
818-7388 <http://www.rettsyndrome.org>.
Koenig, Kathy. ‘‘Frequently Asked Questions.’’ Yale-New
Haven Medical Center Page. <http://
info.med.yale.edu>.

Donald G. Barstow, RN
Teresa G. Odle

PET scan see Positron emission tomography
(PET)

Pet therapy
Definition
Animal-assisted therapy (AAT), also known as
pet therapy, utilizes trained animals and handlers to
GALE ENCYCLOPEDIA OF MEDICINE

Pet therapy
This autistic child is encouraged to interact with the guinea pig in an effort to improve his social interaction. (Helen B. Senisi.
Photo Researchers, Inc. Reproduced by permission.)

achieve specific physical, social, cognitive, and emotional goals with patients.

Purpose
Studies have shown that physical contact with a
pet can lower high blood pressure, and improve survival rates for heart attack victims. There is also evidence that petting an animal can cause endorphins to
be released. Endorphins are chemicals in the body that
suppress the pain response. These are benefits that can
be enjoyed from pet ownership, as well as from visiting
therapeutic animals.
Many skills can be learned or improved with the
assistance of a therapy animal. Patient rehabilitation
can be encouraged by such activities as walking or
running with a dog, or throwing objects for the animal
to retrieve. Fine motor skills may be developed by
petting, grooming, or feeding the animal. Patient communication is encouraged by the response of the animal to either verbal or physical commands. Activities
such as writing or talking about the therapy animals
or past pets also develop cognitive skills and
GALE ENCYCLOPEDIA OF MEDICINE

communication. Creative inclusion of an animal in
the life or therapy of a patient can make a major
difference in the patient’s comfort, progress, and
recovery.

Description
Origins
The enjoyment of animals as companions dates
back many centuries, perhaps even to prehistoric
times. The first known therapeutic use of animals
started in Gheel, Belgium in the ninth century. In
this town, learning to care for farm animals has long
been an important part of an assisted living program
designed for people with disabilities.
Some of the earliest uses of animal-assisted healing in the United States were for psychiatric patients.
The presence of the therapy animals produced a beneficial effect on both children and adults with mental
health issues. It is only in the last few decades that
AAT has been more formally applied in a variety of
therapeutic settings, including schools and prisons, as
2871

Peyronie’s disease

KEY TERMS
Endorphins—A group of chemicals resembling opiates that are released in the body in response to
trauma or stress. Endorphins react with opiate
receptors in the brain to reduce pain sensations.

well as hospitals, hospices, nursing homes, and outpatient care programs.
The way in which AAT is undertaken depends on
the needs and abilities of the individual patient. Dogs
are the most common visiting therapy animals, but
cats, horses, birds, rabbits, and other domestic pets
can be used as long as they are appropriately screened
and trained.
For patients who are confined, small animals can
be brought to the bed if the patient is willing and is
not allergic to the animal. A therapeutic plan may
include a simple interaction aimed at improving communication and small motor skills, or a demonstration with educational content to engage the patient
cognitively.
If the patient is able to walk or move around,
more options are available. Patients can walk small
animals outside, or learn how to care for farm animals.
Both of these activities develop confidence and motor
abilities. Horseback riding has recently gained great
therapeutic popularity. It offers an opportunity to
work on balance, trunk control, and other skills.
Many patients who walk with difficulty, or not at all,
get great emotional benefit from interacting with and
controlling a large animal.
One advantage of having volunteers provide this
service is that cost and insurance are not at issue.

Precautions
AAT does not involve just any pet interacting with
a patient. Standards for the training of the volunteers
and their animals are crucial in order to promote a
safe, positive experience for the patient. Trained
volunteers will understand how to work with other
medical professionals to set goals for the patient and
keep records of progress. Animals that have been
appropriately trained are well socialized to people,
other animals, and medical equipment. They are not
distracted by the food and odors that may be present
in the therapy environment and will not chew inappropriate objects or mark territory.
2872

Animals participating in AAT should be covered
by some form of liability insurance.

Research and general acceptance
While the research evidence supporting the efficacy of AAT is slim, the anecdotal support is vast.
Although it may not be given much credence by medical personnel as a therapy with the potential to assist
the progress of the patients, some institutions do at
least allow it as something that will uplift the patients
or distract them from their discomforts.
Resources
ORGANIZATIONS

Delta Society. <http://www.deltasociety.org>.

Judith Turner

Peyronie’s disease
Definition
Peyronie’s disease is a condition characterized by
a bent penis.

Description
The cause of Peyronie’s disease is unknown and
the disease is often difficult to treat. For some reason,
a thick scar develops in the penis and bends it. Almost
a third of patients with Peyronie’s disease also have
similar contracting scars on their hands, a disease
called Dupuytren’s contractures. Some cases are associated with diabetes, and others appear after prostate
surgery. Because prostate surgery always requires a
catheter in the bladder, there is some suspicion that
catheters can cause the scarring. However, many cases
of Peyronie’s disease arise without any use of a catheter. There is also a congenital form of penile deviation,
again with no known cause. Most of the scars are
located in the mid-line, therefore most of the angulations are either up or down.

Causes and symptoms
Peyronie’s disease occurs in about 1% of men,
most of them between 45–60 years old. Although
there is no good research data to back it up, the suspicion exists that Peyronie’s disease is the result of
injury. If not a catheter, then sudden, forceful bending
GALE ENCYCLOPEDIA OF MEDICINE

Catheter—A flexible tube placed into a body vessel
or cavity.
Congenital—Present at birth.
Plastic surgery—The restoring and reshaping of the
skin and its appendages to improve their function
and appearance.
Prostate—A gland that surrounds the outlet to the
male bladder.
Prosthesis—Artificial substitute for a body part.

during sexual intercourse could easily tear the supporting tissues and lead to scarring.
The symptom is bending of an erect penis, sometimes with pain. It often interferes with sexual intercourse. Erectile failure associated with the angulation
often precedes it.

Treatment
Attempts have been made to reduce the angulation with injections of cortisone-like drugs
directly into the scar, but they are rarely successful.
Surgery seems to be the better answer. After the
scar is removed, plastic repair of the penis is
attempted, often with a graft of tissue from somewhere else on the body. The Nesbit procedure is
one of the more successful methods of doing this.
The other surgical approach is to implant a penile
prosthesis that overcomes the angulation mechanically. Results with these procedures are reported to
be 60–80% satisfactory, including the return of
orgasm.

Prognosis
Sometimes the condition disappears spontaneously. A careful look for other causes of impotence
should be done before surgery.
Resources
BOOKS

Jordan, Gerald H., et al. ‘‘Surgery of the Penis and
Urethra.’’ InCampbell’s Urology, edited by Patrick C.
Walsh, et al. Philadelphia: W. B. Saunders Co., 1998.

J. Ricker Polsdorfer, MD
GALE ENCYCLOPEDIA OF MEDICINE

Pharmacogenetics
Definition
Pharmacogenetics is the study of how the actions
of and reactions to drugs vary with the patient’s
genes.

Description
Genes are the portions of chromosomes that
determine many of the traits in every living thing. In
humans, genes influence race, hair and eye color, gender, height, weight, aspects of behavior, and even the
likelihood of developing certain diseases. Although
some traits are a combination of genetics and environment, researchers are still discovering new ways in
which people are affected by their genes.
Pharmacogenetics is the study of how people
respond to drug therapy. Although this science is still
new, there have been many useful discoveries. It has
long been known that genes influence the risk of developing certain diseases, or that genes could determine
traits such as hair and eye color. Genes can also alter
the risk of developing different diseases. It has long
been known that people of African descent were more
likely to have sickle cell anemia than people of other
races. People of Armenian, Arab, and Turkish heritage are more prone to familiar Mediterranean fever
than people of other nationalities. More recently, discoveries have shown that genes can determine other
aspects of each individual, down to the level of the
enzymes produced in the liver. Since these enzymes
determine how quickly a drug is removed from the
body, they can make major differences in the way
people respond to drugs. Some of the most basic
work concerns the way race and gender influence
drug reactions—and race and gender are genetically
determined.
Women often respond differently than men to
drugs at the same dose levels. For example, women
are more likely to have a good response to the antidepressant drugs that act as serotonin specific reuptake inhibitors (SSRIs, the group that includes
Prozac and Paxil) than they are to the older group
of tricyclic antidepressants (the group that includes
Elavil and Tofranil). Women have a greater response
to some narcotic pain reliving drugs than do men, but
get less relief from some non-narcotic pain medications. Women may show a greater response to some
steroid hormones than men do, but have a lower level
of response to some anti-anxiety medications
than men.
2873

Pharmacogenetics

KEY TERMS

Pharmacogenetics

Race may also affect the way people respond to
some medications. In this case, race implies specific
genetic factors that are generally, but not always,
found among members of specific ethnic groups. For
example, the angiotensin II inhibitor enalopril
(Vasotec), which is used to lower blood pressure,
works better in Caucasians than in Blacks.
Carvedilol (Coreg), a beta-adrenergic blocking agent
that is also used to lower blood pressure, is more
effective than other drugs in the same class when
used to treat Black patients. Black patients with
heart failure appear to respond better to a combination of hydralazine and isosorbide than do Caucasian
patients using the same medication.
More specific research has identified individual
genes than may influence drugs response, without
relying on group information such as gender and
race. Specific genes have been identified that may
determine how patients will respond to specific
drugs. For example, some genes may determine
whether people will get pain relief from codeine, or
how well they will respond to drugs used to treat
cancer.

Causes and symptoms
Genes alter responses to drugs because the genes
influence many parts of the body iteself. One of the
simplest examples is the gene that influences body
weight. Since many drugs are soluble in body fat,
people with large amounts of fat will have these drug
deposited into their fat stores. This means that there
are lower levels of the drug that can reach the actual
organs on which they work.
In the case of gender responses to antidepressants,
women show greater response to serotonin specific
antidepressants because women naturally have lower
levels of serotonin than men do. This makes women
more likely to develop a type of depression marked by
low serotonin levels, but it also means that women will
respond better to replacement of serotonin.
Because people of the same race carry similar
genes, studies based on race were the earliest types of
pharmacogenetic studies. One study evaluated the
levels of alcohol dehydrogenase in people of different
nationalities. This is an enzyme involved in the metabolism of alcohol. When people with high levels of this
enzyme, or people in whom the enzyme acts more
rapidly than in other people, drink alcohol, they are
subject to facial flushing and slowing of the heartbeat.
The activity of this enzyme is determined by genetics,
and different levels can be seen in different races
because these people belong to the same gene pools.
2874

Among Asiatic people, 85% have high levels of this
enzyme, compared to 20% of Swiss people, and only
5–10% of British people.
Another trait that is influenced by genes is a liver
enzyme, CYP2D6. This enzyme metabolizes some
drugs, convert them to a form that can be removed
from the body. Genes determine the level of this
enzyme in the liver. People with low levels of
CYP2D6 will metabolize drugs slowly. Slow metabolism means the drugs will act for a longer period of
time. Slow metabolizers reaspond to smaller doses of
medications that are eliminated by this enzyme, while
fast metabolizers, people who have a lot of the
enzyme, will need larger drug doses to get the same
effects. At the same time, low levels of CYP2D6 means
that people taking the drugs that are metabolized by
this enzyme will have higher drug levels, and are more
likely to have unwanted side effects.
Another enzyme that can be important in drug
dosing is called 2C9, and this enzyme is responsible
for metabolizing the anticoagulant drug warfarin
(Coumadin). Most people take warfarin in a dose of
about 5 milligrams a day, but people who have low
levels of 2C9 normally require a dose of only 1–5
milligrams a week.
Yet another mechanism of drug activity is the
presence or absence of a specific drug receptor site.
Drugs act by binding to specific chemicals, receptor
sites, within body cells. Genes may help determine
how many of these cells there are. The action of the
widely used antipsychotic drug haloperidol (Haldol)
depends on its ability to bind to the dopamine (D2)
receptor site. The number of these sites are determined
by genetics. In one study, 63% of patients whose genes
caused a large number of these receptor sites had a
response to treatment with haloperidol, while only
about 29% of patients with a smaller number of dopamine (D2) receptor sites did well on the drug.
Other genetic studies indicate that genes may
affect how people respond to foods as well as to
drugs. An Australian study of osteoporosis (softening
of the bones that often occurs in elderly people),
reported that separate genes may affect response to
vitamin D, calcium, and estrogens.
Implications
Although the study is still new, pharmacogenetics
promises to offer great benefits in drug effectiveness
and safety.
At the present time, most drug treatment is done
by trial and error. Physicians prescribe medication,
and the patient tries the drug. The drug may work,
GALE ENCYCLOPEDIA OF MEDICINE

Enzyme—Proteins produced by living cells that
help produce specific biochemical reactions in
the body.
Metabolism—The process by which foods and
drugs are broken down for use and removal from
the body.
Sickle cell anemia—A severe, inheritable disease,
most common among people of African descent,
marked by deformation and destruction of red
blood cells, and by adherence of blood cells to
the walls of blood vessels.

University of California, Los Angeles Harbor-UCLA
Medical Center Research and Education Institute 1124
W Carson St., B-4 South Torrance, CA 90502.

Samuel D. Uretsky, PharmD

Pharyngeal pouch see Esophageal pouches
Pharyngitis see Sore throat
Phenelzine see Monoamine oxidase
inhibitors
Phenobarbital see Barbiturates
Phenol see Antiseptics
Phenolphthalein see Laxatives

or it may not. It may cause adverse effects, or it may be
safe. If the drug does not work, the dose is increased. If
it causes harmful or unpleasant effects, a new drug is
tried until, finally, the right drug is found. In some
cases this procedure may take weeks or even months.
In other cases, drugs are carefully tested, and
appear to be safe and effective. Only after they are
approved for general use are reports of serious adverse
effects that did not appear in the initial studies documented. This can occur if there is a rare gene that
affects the way in which the drug acts, or the way in
which the drug is metabolized.
With increasing understanding of how genes
determine the way people respond to drugs, it will be
possible to select drugs and doses based on a greater
understanding of each individual patient. This promises more effective drug therapy, with greater safety
and fewer treatment failures.
Physicians may be able to compare the person’s
genetic make-up with the properties of specific drugs,
and make informed decisions about which drug in a
group will work most effectively or most safely.
Resources
BOOKS

From Genome to Therapy: Integrating New Technologies with
Drug Development. New York: John Wiley, 2000.
PERIODICALS

‘‘A DNA tragedy.’’ Fortune October 30, 2000.
‘‘Screening for genes.’’ Newsweek February 8, 1999.
ORGANIZATIONS

National Institute of General Medical Sciences. Division of
Pharmacology, Physiology, and Biological Chemistry.
45 Center Dr., MSC 6200 Bethesda, MD 20892-6200.
GALE ENCYCLOPEDIA OF MEDICINE

Phenylalaninemia see Phenylketonuria

Phenylketonuria
Definition
Phenylketonuria (PKU) can be defined as a rare
metabolic disorder caused by a deficiency in the production of the hepatic (liver) enzyme phenylalanine
hydroxylase (PAH). PKU is the most serious form of
a class of diseases referred to as ‘‘hyperphenylalaninemia,’’ all of which involve above normal (elevated)
levels of phenylalanine in the blood. The primary
symptom of untreated PKU, mental retardation, is
the result of consuming foods that contain the amino
acid phenylalanine, which is toxic to brain tissue.
PKU is an inherited, autosomal recessive disorder. It is the most common genetic disease involving
‘‘amino acid metabolism.’’ PKU is incurable, but
early, effective treatment can prevent the development
of serious mental incapacity.

Description
PKU is a disease caused by the liver’s inability to
produce a particular type of PAH enzyme. This
enzyme converts (metabolizes) the amino acid called
phenylalanine into another amino acid, tyrosine. This
is the only role of PAH in the body. A lack of PAH
results in the buildup of abnormally high phenylalanine concentrations (or levels) in the blood and brain.
Above normal levels of phenylalanine are toxic to the
cells that make up the nervous system and causes
irreversible abnormalities in brain structure and function in PKU patients. Phenylalanine is a type of
2875

Phenylketonuria

KEY TERMS

Phenylketonuria

teratogen. Teratogens are any substance or organism
that can cause birth defects in a developing fetus.
The liver is the body’s chief protein processing
center. Proteins are one of the major food nutrients.
They are generally very large molecules composed of
strings of smaller building blocks or molecules called
amino acids. About twenty amino acids exist in nature. The body breaks down proteins from food into
individual amino acids and then reassembles them into
‘‘human’’ proteins. Proteins are needed for growth
and repair of cells and tissues, and are the key components of enzymes, antibodies, and other essential
substances.
PKU affects on the human nervous system
The extensive network of nerves in the brain and
the rest of the nervous system are made up of nerve
cells. Nerve cells have specialized extensions called
dendrites and axons. Stimulating a nerve cell triggers
nerve impulses, or signals, that speed down the axon.
These nerve impulses then stimulate the end of an
axon to release chemicals called ‘‘neurotransmitters’’
that spread out and communicate with the dendrites of
neighboring nerve cells.
Many nerve cells have long, wire-like axons that
are covered by an insulating layer called the myelin
sheath. This covering helps speed nerve impulses along
the axon. In untreated PKU patients, abnormally high
phenylalanine levels in the blood and brain can produce nerve cells with ‘‘deformed’’ axons and dendrites,
and cause imperfections in the myelin sheath referred
to as hypomyelination and demylenation. This loss of
myelin can ‘‘short circuit’’ nerve impulses (messages)
and interrupt cell communication. A number of brain
scan studies also indicate a degeneration of the ‘‘white
matter’’ in the brains of older patients who have not
maintained adequate dietary control.
PKU can also affect the production of one of the
major neurotransmitters in the brain, called dopamine. The brain makes dopamine from the amino
acid tyrosine. PKU patients who do not consume
enough tyrosine in their diet cannot produce sufficient
amounts of dopamine. Low dopamine levels in the
brain disrupt normal communication between nerve
cells, which results in impaired cognitive (mental)
function.
Some preliminary research suggests that nerve
cells of PKU patients also have difficulty absorbing
tyrosine. This abnormality may explain why many
PKU patients who receive sufficient dietary tyrosine
still experience some form of learning disability.
2876

Behavior and academic performance
IQ (intelligence quotient) tests provide a measure
of cognitive function. The IQ of PKU patients is generally lower than the IQ of their healthy peers.
Students with PKU often find academic tasks difficult
and must struggle harder to succeed than their nonPKU peers. They may require special tutoring and
need to repeat some of their courses. Even patients
undergoing treatment programs may experience problems with typical academic tasks as math, reading,
and spelling. Visual perception, visual-motor skills,
and critical thinking skills can also be affected. Ten
years of age seems to be an important milestone for
PKU patients. After age 10, variations in a patient’s
diet seems to have less influence on their IQ
development.
People with PKU tend to avoid contact with
others, appear anxious and show signs of depression.
However, some patients may be much more expressive
and tend to have hyperactive, talkative, and impulsive
personalities. It is also interesting to note that people
with PKU are less likely to display such ‘‘antisocial’’
habits as lying, teasing, and active disobedience. It
should be emphasized that current research findings
are still quite preliminary and more extensive research
is needed to clearly show how abnormal phenylalanine
levels in the blood and brain might affect behavior and
academic performance.
One in fifty individuals in the United States have
inherited a gene for PKU. About five million
Americans are PKU carriers. About one in 15,000
babies test positive for PKU in the United States.
Studies indicate that the incidence of this disease in
Caucasian and Native American populations is higher
than in African-American, Hispanic, and Asian
populations.

Causes and symptoms
PKU symptoms are caused by alterations or
‘‘mutations’’ in the genetic code for the PAH enzyme.
Mutations in the PAH gene prevent the liver from
producing adequate levels of the PAH enzyme needed
to break down phenylalanine. The PAH gene and its
PKU mutations are found on chromosome 12 in the
human genome. In more detail, PKU mutations can
involve many different types of changes, such as deletions and insertions, in the DNA of the gene that codes
for the PAH enzyme.
PKU is described as an inherited, autosomal
recessive disorder. The term autosomal means that
the gene for PKU is not located on either the X or Y
GALE ENCYCLOPEDIA OF MEDICINE

A person with one normal and one PKU gene is
called a carrier. A carrier does not display any symptoms of the disease because their liver produces normal quantities of the PAH enzyme. However, PKU
carriers can pass the PKU genetic mutation onto their
children. Two carrier parents have a 25% chance of
producing a baby with PKU symptoms, and a 50%
chance having a baby that is a carrier for the disease.
Although PKU conforms to these basic genetic patterns of inheritance, the actual expression, or phenotype, of the disease is not strictly an ‘‘either/or’’
situation. This is because there are at least 400 different types of PKU mutations. Although some PKU
mutations cause rather mild forms of the disease,
others can initiate much more severe symptoms in
untreated individuals. The more severe the PKU
mutation, the greater the effect on cognitive development and performance (mental ability).
Untreated PKU patients develop a broad range of
symptoms related to severely impaired cognitive function, sometimes referred to as mental retardation.
Other symptoms can include extreme patterns of behavior, delayed speech development, seizures, a characteristic body odor, and light body pigmentation. The
light pigmentation is due to a lack of melanin, which
normally colors the hair, skin and eyes. Melanin is
made from the amino acid tyrosine, which is lacking
in untreated cases of PKU. Physiologically, PKU
patients show high levels of phenylalanine and low
levels of tyrosine in the blood. Babies do not show
any visible symptoms of the disease for the first few
months of life. However, typical PKU symptoms
usually do show up by a baby’s first birthday.

Diagnosis
The primary diagnostic test for PKU is the measurement of phenylalanine levels in a drop of blood taken
from the heel of a newborn baby’s foot. This screening
procedure is referred to as the Guthrie test (Guthrie
bacterial inhibition assay). In this test, PKU is confirmed
by the appearance of bacteria growing around high concentrations of phenylalanine in the blood spot. PKU
testing was introduced in the early 1960s and is the largest
genetic screening program in the United States. It is
required by law in all 50 states. Early diagnosis is critical.
It ensures early the treatment PKU babies need to
develop normally and avoid the ravages of PKU.
GALE ENCYCLOPEDIA OF MEDICINE

The American Academy of Pediatrics recommends that this test should be performed on infants
between 24 hours and seven days after birth. The
preferred time for testing is after the baby’s first feeding. If the initial PKU test produces a positive result,
then follow-up tests are performed to confirm the
diagnosis and to determine if the elevated phenylalanine levels may be caused by some medical condition
other than PKU. Treatment for PKU is recommended
for babies that show a blood phenylalanine level of 7–
10 mg/dL or higher for more than a few consecutive
days. Another, more accurate test procedure for PKU
measures the ratio (comparison) of the amount of
phenylalanine to the amount of tyrosine in the blood.
Newer diagnostic procedures (called mutation
analysis and genotype determination) can actually
identify the specific types of PAH gene mutations
inherited by PKU infants. Large-scale studies have
helped to clarify how various mutations affect the
ability of patients to process phenylalanine. This information can help doctors develop more effective customized treatment plans for each of their PKU patients.

Treatment
The severity of the PKU symptoms experienced
by people with this disease is determined by both lifestyle as well as genetic factors. In the early 1950s,
researchers first demonstrated that phenylalaninerestricted diets could eliminate most of the typical
PKU symptoms—except for mental retardation.
Today, dietary therapy (also called nutrition therapy)
is the most common form of treatment for PKU
patients. PKU patients who receive early and consistent dietary therapy can develop fairly normal mental
capacity to within about five IQ points of their healthy
peers. By comparison, untreated PKU patients generally have IQ scores below 50.
Infants with PKU should be put on a specialized
diet as soon as they are diagnosed to avoid progressive
brain damage and other problems caused by an accumulation of phenylalanine in the body. A PKU diet
helps patients maintain very low blood levels of phenylalanine by restricting the intake of natural foods
that contain this amino acid. Even breast milk is a
problem for PKU babies. Special PKU dietary mixtures or formulas are usually obtained from medical
clinics or pharmacies.
Phenylalanine is actually an essential amino acid.
This means that it has to be obtained from food
because the body cannot produce this substance on
its own. Typical diets prescribed for PKU patients
provide very small amounts of phenylalanine and
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Phenylketonuria

sex chromosome. The normal PAH gene is dominant
to recessive PKU mutations. A recessive genetic trait,
such as PKU, is one that is expressed—or shows up—
only when two copies are inherited (one from each
parent).

Phenylketonuria

higher quantities of other amino acids, including tyrosine. The amount of allowable phenylalanine can be
increased slightly as a child becomes older.

by the patient. This medication would be taken orally
and could prevent the absorption of digested phenylalanine into the patient’s bloodstream.

In addition, PKU diets include all the nutrients
normally required for good health and normal
growth, such as carbohydrates, fats, vitamins, and
minerals. High protein foods like meat, fish, chicken,
eggs, nuts, beans, milk, and other dairy products are
banned from PKU diets. Small amounts of moderate
protein foods (such as grains and potatoes) and low
protein foods (some fruits and vegetables, low protein
breads and pastas) are allowed. Sugar-free foods, such
as diet soda, which contain the artificial sweetener
aspartame, are also prohibited foods for PKU
patients. That is because aspartame contains the
amino acid phenylalanine.

In general, medical researchers express concern
about the great variation in treatment programs currently available to PKU patients around the world.
They have highlighted the urgent need for new, consistent international standards for proper management of PKU patients, which should emphasize
comprehensive psychological as well as physiological
monitoring and assessment.

Ideally, school-age children with PKU should be
taught to assume responsibility for managing their
diet, recording food intake, and for performing simple
blood tests to monitor their phenylalanine levels.
Blood tests should be done in the early morning
when phenylalanine levels are highest. Infants and
young children require more frequent blood tests
than older children and adults. The amount of natural
foods allowed in a diet could be adjusted to ensure that
the level of phenylalanine in the blood is kept within a
safe range—two to 6 mg/dL before 12 years of age and
2–15 mg/dL for PKU patients over 12 years old.
A specialized PKU diet can cause abnormal fluctuations in tyrosine levels throughout the day. Thus,
some health professionals recommend adding time
released tyrosine that can provide a more constant
supply of this amino acid to the body. It should be
noted that some PKU patients show signs of learning
disabilities even with a special diet containing extra
tyrosine. Research studies suggests that these PKU
patients may not be able to process tyrosine normally.
For PKU caregivers, providing a diet that is
appealing as well as healthy and nutritious is a constant challenge. Many PKU patients, especially teenagers, find it difficult to stick to the relatively bland
PKU diet for extended periods of time. Some older
patients decide to go off their diet plan simply because
they feel healthy. However, many patients who abandon careful nutritional management develop cognitive
problems, such as difficulties remembering, maintaining focus, and paying attention. Many PKU health
professionals contend that all PKU patients should
adhere to a strictly controlled diet for life.
One promising line of PKU research involves the
synthesis (manufacturing) of a new type of enzyme
that can break down phenylalanine in food consumed
2878

PKU and Pregnancy
Women with PKU must be especially careful with
their diets if they want to have children. They should
ensure that phenylalanine blood levels are under control before conception and throughout her pregnancy.
Mothers with elevated (higher than normal) phenylalanine levels are high risk for having babies with
significant birth defects, such as microencephaly
(smaller than normal head size), and congenital heart
disease (abnormal heart structure and function),
stunted growth, mental retardation, and psychomotor
(coordination) difficulties. This condition is referred
to as maternal PKU and can even affect babies who
do not have the PKU disease.

Prognosis
Early newborn screening, careful monitoring, and
a life-long strict dietary management can help PKU
patients to live normal, healthy, and long lives.
Resources
BOOKS

Brust, John C. M. The Practice Of Neural Science: From
Synapses To Symptoms. New York: McGraw-Hill,
2000.
Gilroy, John. Basic Neurology. 3rd ed. New York: McGrawHill, 2000.
Ratey, John J. A User’s Guide To The Brain: Perception,
Attention, And The Four Theaters Of The Brain. 1st ed.
New York: Pantheon Books, 2001.
Weiner, William J., and Christopher G. Goetz, editors.
Neurology For The Non-Neurologist. 4th ed.
Philadelphia: Lippincott, Williams & Wilkins, 1999.
PERIODICALS

Burgard, P. ‘‘Development of intelligence in early treated
phenylketonuria.’’ European Journal of Pediatrics 159,
Supplement 2 (October 2000): S74–9.
Chang, Pi-Nian, Robert M. Gray, and Lisa Lehn O’Brien.
‘‘Review: Patterns of academic achievement among
patients treated early with phenylketonuria.’’ European
Journal of Pediatrics 159, no.14 (2000): S96–9.
GALE ENCYCLOPEDIA OF MEDICINE

Amino acid—Organic compounds that form the
building blocks of protein. There are 20 types of
amino acids (eight are ‘‘essential amino acids’’
which the body cannot make and must therefore
be obtained from food).
Axon—Skinny, wire-like extension of nerve cells.
Enzyme—A protein that catalyzes a biochemical
reaction or change without changing its own structure or function.
Gene—A building block of inheritance, which
contains the instructions for the production of a
particular protein, and is made up of a molecular
sequence found on a section of DNA. Each gene is
found on a precise location on a chromosome.
Genetic disease—A disease that is (partly or completely) the result of the abnormal function or
expression of a gene; a disease caused by the
inheritance and expression of a genetic mutation.
IQ—Abbreviation for Intelligence Quotient.
Compares an individual’s mental age to his/her true
or chronological age and multiplies that ratio by 100.
Metabolism—The total combination of all of the
chemical processes that occur within cells and tissues of a living body.
Mutation—A permanent change in the genetic
material that may alter a trait or characteristic of
an individual, or manifest as disease, and can be
transmitted to offspring.
Myelin—A fatty sheath surrounding nerves in the
peripheral nervous system, which help them conduct impulses more quickly.
Nervous system—The complete network of nerves,
sense organs, and brain in the body.
Phenylalanine—An essential amino acid that must
be obtained from food since the human body cannot manufacture it.
Protein—Important building blocks of the body,
composed of amino acids, involved in the formation of body structures and controlling the basic
functions of the human body.
Recessive—Genetic trait expressed only when present on both members of a pair of chromosomes,
one inherited from each parent.

Eastman, J.W., J.E. Sherwin, R. Wong, C.L. Liao, R.J.
Currier, F. Lorey, and G. Cunningham. ‘‘Use of the
phenylalanine:tyrosine ratio to test newborns for
GALE ENCYCLOPEDIA OF MEDICINE

phenylketonuria in a large public health screening programme.’’ Journal of Medical Screening 7, no. 3 (2000):
131–5.
MacDonald, A. ‘‘Diet and compliance in phenylketonuria.’’
European Journal of Pediatrics 159, Supplement 2
(October 2000): S136–41.
Smith, Isabel, and Julie Knowles. ‘‘Behaviour in early treated phenylketonuria: a systematic review.’’ European
Journal of Pediatrics 159, no. 14 (2000): S89–93.
Stemerdink, B.A., A.F. Kalverboer, J.J. van der Meere,
M.W. van der Molen, J. Huisman, L.W. de Jong, F.M.
Slijper, P.H. Verkerk, and F.J. van Spronsen.
‘‘Behaviour and school achievement in patients with
early and continuously treated phenylketonuria.’’
Journal of Inherited Metabolic Disorders 23, no. 6
(2000): 548–62.
van Spronsen, F.J.F., M.M. van Rijn, J. Bekhof, R. Koch,
and P.G. Smit. ‘‘Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets.’’ American
Journal of Clinical Nutrition 73, no. 2 (2001): 153–7.
Wappner, Rebecca, Sechin Cho, Richard A. Kronmal,
Virginia Schuett, and Margretta Reed Seashore.
‘‘Management of Phenylketonuria for Optimal
Outcome: A Review of Guidelines for Phenylketonuria
Management and a Report of Surveys of Parents,
Patients, and Clinic Directors.’’ Pediatrics 104, no. 6
(December 1999): e68.
ORGANIZATIONS

American Academy of Allergy, Asthma & Immunology. 611
E. Wells St, Milwaukee, WI 53202. (414) 272-6071. Fax:
(414) 272-6070. <http://www.aaaai.org/default.stm>.
Centers for Disease Control. GDP Office, 4770 Buford
Highway NE, Atlanta, GA 30341-3724. (770) 488-3235.
<http://www.cdc.gov/genetics>.
Children’s PKU Network. 1520 State St., Suite 111, San
Diego, CA 92101-2930. (619) 233-3202. Fax: (619) 233
0838. pkunetwork@aol.com.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (888) 6634637. resourcecenter@modimes.org. <http://
www.modimes.org>.
National PKU News. Virginia Schuett, editor/dietician.
6869 Woodlawn Avenue NE #116, Seattle, WA 981155469. (206) 525-8140. Fax: (206) 525-5023. <http://
www.pkunews.org>.
University of Washington PKU Clinic. CHDD, Box 357920,
University of Washington, Seattle, WA. (206) 685-3015.
Within Washington State: (877) 685-3015. Clinic
Coordinator: vam@u.washington.edu. <http://depts.washington.edu/pku/contact.html.>.
OTHER

Allergy and Asthma Network. Mothers of Asthmatics, Inc.
2751 Prosperity Ave., Suite 150, Fairfax, VA 22031.
(800) 878-4403. Fax: (703)573-7794.
Consensus Development Conference on Phenylketonuria
(PKU): Screening and Management, October 16–18,
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Phenylketonuria

KEY TERMS

Pheochromocytoma

2000. <http://odp.od.nih.gov/consensus/news/upcoming/pku/pku_info.htm#overview>.
Genetics and Public Health in the 21st Century. Using
Genetic Information to Improve Health and Prevent
Disease. <http://www.cdc.gov/genetics/_archive/publications/Table>.

Marshall G. Letcher, MA

Phenylpropanolamine see Decongestants
Phenytoin see Anticonvulsant drugs

Pheochromocytoma
Definition
Pheochromocytoma is a tumor of special cells
(called chromaffin cells), most often found in the middle of the adrenal gland.

Description
Because pheochromocytomas arise from chromaffin cells, they are occasionally called chromaffin
tumors. Most (90%) are benign tumors so they do not
spread to other parts of the body. However, these
tumors can cause many problems and if they are not
treated and can result in death.
Pheochromocytomas can be found anywhere
chromaffin cells are found. They may be found in the
heart and in the area around the bladder, but most
(90%) are found in the adrenal glands. Every individual has two adrenal glands that are located above the
kidneys in the back of the abdomen. Each adrenal
gland is made up of two parts: the outer part (called
the adrenal cortex) and the inner part (called the adrenal medulla). Pheochromocytomas are found in the
adrenal medulla. The adrenal medulla normally
secretes two substances, or hormones, called norepinephrine and epinephrine. These two substances,
when considered together, are known as adrenaline.
Adrenaline is released from the adrenal gland, enters
the bloodstream and helps to regulate many things in
the body including blood pressure and heart rate.
Pheochromocytomas cause the adrenal medulla to
secrete too much adrenaline, which in turn causes
high blood pressure. The high blood pressure usually
causes the other symptoms of the disease.
Pheochromocytomas are rare tumors. They have
been reported in babies as young as five days old as
well as adults 92 years old. Although they can be found
2880

at any time during life, they usually occur in adults
between 30 and 40 years of age. Pheochromocytomas
are somewhat more common in women than in men.

Causes and symptoms
The cause of most pheochromocytomas is not
known. A small minority (about 10-20%) of pheochromocytomas arise because a person has an inherited
susceptibility to them. Inherited pheochromocytomas
are associated with four separate syndromes: Multiple
Endocrine Neoplasia, type 2A (MEN2A), Multiple
Endocrine Neoplasia, type 2B (MEN2B), von HippelLindau disease (VHL) and Neurofibromatosis type 1
(NF1).
Individuals with pheochromocytomas as part of
any of these four syndromes usually have other medical conditions as well. People with MEN2A often
have cancer (usually thyroid cancer) and other hormonal problems. Individuals with MEN2B can also have
cancer and hormonal problems, but also have other
abnormal physical features. Both MEN2A and
MEN2B are due to genetic alterations or mutations
in a gene called RET, found at chromosome 10q11.2.
Individuals with VHL often have other benign tumors
of the central nervous system and pancreas, and can
sometimes have renal cell cancer. This syndrome is
caused by a mutation in the VHL gene, found at
chromosome 3p25-26. Individuals with NF1 often
have neurofibromas (benign tumors of the peripheral
nervous system). NF1 is caused by mutations in the
NF1 gene, found at chromosome 17q11.
All of these disorders are inherited in an autosomal dominant inheritance pattern. With autosomal
dominant inheritance, men and women are equally
likely to inherit the syndrome. In addition, children
of individuals with the disease are at 50% risk of
inheriting it. Genetic testing is available for these four
syndromes (MEN2A, MEN2B, VHL and NF1) but,
due to the complexity, genetic counseling should be
considered before testing.
Most people (90%) with pheochromocytoma
have hypertension, or high blood pressure. The other
symptoms of the disease are extremely variable. These
symptoms usually occur in episodes (or attacks) called
paroxysms and include:


headaches



excess sweating



racing heart



rapid breathing



anxiety/nervousness
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nervous shaking



pain in the lower chest or upper abdomen



nausea



heat intolerance

The episodes can occur as often as 25 times a day
or, as infrequently as once every few months. They can
last a few minutes, several hours, or days. Usually, the
attacks occur several times a week and last for about
15 minutes. After the episode is over, the person feels
exhausted and fatigued.
Between the attacks, people with pheochromocytoma can experience the following:


increased sweating



cold hands and feet



weight loss



constipation

Diagnosis
If a pheochromocytoma is suspected, urine and/or
a blood test are usually recommended. A test called
‘‘24-hour urinary catacholamines and metanephrines’’
will be done. This test is designed to look for adrenaline and the break-down products of adrenaline. Since
the body gets rid of these hormones in the urine, those
testing will need to collect their urine for 24 hours. The
laboratory will determine whether or not the levels of
hormones are too high. This test is very good at making the diagnosis of pheochromocytoma. Another test
called ‘‘serum catacholamines’’ measures the level of
adrenaline compounds in the blood. It is not as sensitive as the 24-hour urine test, but can still provide
some key information if it shows that the level of
adrenaline compounds is too high.
One of the difficulties with these tests is that a
person needs to have an attack of symptoms either
during the 24-hour urine collection time period or
shortly before the blood is drawn for a serum test to
ensure the test’s accuracy. If a person did not have
an episode during that time, the test can be a ‘‘false
negative’’. If a doctor suspects the patient has had a
‘‘false negative’’ test, additional tests called ‘‘pharmacologic tests’’ can be ordered. During these tests, a
specific drug is given to the patient (usually through
an IV) and the levels of hormones are monitored from
the patient’s blood. These types of tests are only done
rarely.
Once a person has been diagnosed with a pheochromocytoma, he or she will undergo tests to identify
exactly where in the body the tumor is located. The
GALE ENCYCLOPEDIA OF MEDICINE

imaging techniques used are usually computed tomography scan (CT scan) and magnetic resonsance imaging (MRI). A CT scan creates pictures of the interior
of the body from computer-analyzed differences in
x rays passing through the body. CT scans are performed at a hospital or clinic and take only a few
minutes. An MRI is a computerized scanning method
that creates pictures of the interior of the body using
radio waves and a magnet. An MRI is usually performed at a hospital and takes about 30 minutes.

Treatment
Once a pheochromocytoma is found, more tests
will be done to see if the tumor is benign (not cancer)
or malignant (cancer). If the tumor is malignant, tests
will be done to see how far the cancer has spread.
There is no accepted staging system for pheochromocytoma; but an observation of the tumor could provide one of these four indications:


Localized benign pheochromocytoma means that
the tumor is found only in one area, is not cancer,
and cannot spread to other tissues of the body.



Regional pheochromocytoma means that the tumor
is malignant and has spread to the lymph nodes
around the original cancer. Lymph nodes are small
structures found all over the body that make and
store infection-fighting cells.



Metastatic pheochromocytoma means that the
tumor is malignant and has spread to other, more
distant parts of the body.



Recurrent pheochromocytoma means that a malignant tumor that was removed has come back.

Treatment in all cases begins with surgical
removal of the tumor. Before surgery, medications
such as alpha-adrenergic blockers are given to block
the effect of the hormones and normalize blood pressure. These medications are usually started seven to 10
days prior to surgery. The surgery of choice is laparoscopic laparotomy, which is a minimally invasive outpatient procedure performed under general or local
anesthesia. A small incision is made in the abdomen,
the laparoscope is inserted, and the tumor is removed.
The patient can usually return to normal activities
within two weeks. If a laparoscopic laparotomy cannot be done, a traditional laparotomy will be performed. This is a more invasive surgery done under
spinal or general anesthesia and requires five to seven
days in the hospital. Usually patients are able to return
to normal activities after four weeks. After surgery,
blood and urine tests will be done to make sure hormone levels return to normal. If the hormone levels are
2881

Pheochromocytoma



Phimosis

KEY TERMS
Adrenal medulla—The central core of the adrenal
gland.
Laparoscope—An instrument used to examine
body cavities during certain types of surgery; for
example, surgeries to remove fibroid tumors, or gall
bladders, are often removed through the navel
rather than cutting into the body.
Paroxysm—A sudden attack of symptoms.

David Gardner. NewYork: Lange Medical Books/
McGraw-Hill, 2001, pp. 399–421.
Keiser, Harry R. ‘‘Pheochromocytoma and Related
Tumors.’’. In Endocrinology, edited by Leslie J.
DeGroot and J. LarryJameson, 4th ed. New York:
W.B. Saunders Company, 2001,pp. 1862–1883.
PERIODICALS

Barzon, Luisa, and Marco Boscaro. ‘‘Diagnosis and
Management of Adrenal Incidentalomas.’’ The Journal
of Urology 163 (February 2000): 398–407.
Young, William F. ‘‘Management Approaches to
AdrenalIncidentaloma’’ Endocrinology and Metabolism
Clinics of North America 29 (March 2000): 159–185.
OTHER

still above normal, it may mean that some tumor tissue
was not removed. If not all tumor can be removed
(as in malignant pheochromocytoma, for example)
drugs will be given to control high blood pressure.
If a pheochromocytoma is malignant, radiation
therapy and/or chemotherapy may be used. Radiation
therapy uses high-energy x rays to kill cancer cells and
shrink tumors. Because there is no evidence that radiation therapy is effective in the treatment of malignant
pheochromocytoma, it is not often used for treatment.
However, it is useful in the treatment of painful bone
metastases if the tumor has spread to the bones.
Chemotherapy uses drugs to kill cancer cells. Like
radiation therapy, it has not been shown to be effective
in the treatment of malignant pheochromocytoma.
Chemotherapy, therefore, is only used in rare
instances.
Untreated pheochromocytoma can be fatal due to
complications of the high blood pressure. In the vast
majority of cases, when the tumor is surgically
removed, pheochromocytoma is cured. In the minority of cases (10%) where pheochromocytoma is malignant, prognosis depends on how far the cancer has
spread, and the patient’s age and general health. The
overall median five-year survival from the initial time
of surgery and diagnosis is approximately 43%.

Prevention
Unfortunately, little is known about environmental and other causes of pheochromocytoma. Some of
the tumors are due to inherited predisposition.
Because of these factors, pheochromocytoma can not
be prevented.
Resources
BOOKS

Goldfien, Alan. ‘‘Adrenal Medulla.’’ In Basic and Clinical
Endocrinology, edited by Francis Greenspan and
2882

‘‘Pheochromocytoma’’ National CancerInstitute CancerWeb
June 29, 2001. <http://www.graylab.ac.uk/cancernet/
202494.html>.

Lori De Milto
Kristen Mahoney Shannon, M.S. CGC

Phimosis
Definition
A tightening of the foreskin of the penis that may
close the opening of the penis.

Description
The foreskin of a newborn boy is always closely
contracted around the penis head (glans). Only a small
passage allows the urine to pass through. In the first
months the foreskin is stuck to the glans and cannot be
pulled back and one should not attempt to do so.
During the first couple of years, the foreskin will
become gradually looser and in many boys it can in
time be pulled back without trouble. Half of all
three-year-olds can pull back their foreskin. It is
not advisable to try pulling the foreskin back using
force, since this may cause small cuts in the foreskin
with scars which could finally cause a regular foreskin
contraction.
Foreskin contraction, called phimosis, can last
throughout life and not cause any trouble at all. It is
a voluntary decision whether to have a circumcision
operation or not. If any problems do arise, they
happen after puberty. The contraction may occur for
the first time as an adult and usually requires circumcision, the surgical removal of the foreskin.
GALE ENCYCLOPEDIA OF MEDICINE

Phimosis is caused by the inability of the foreskin
to retract from around the opening of the penis. In
adults, phimosis can lead to chronic inflammation and
cancer.

Diagnosis
A physician usually diagnoses phimosis when
there are persistent problems urinating, when there
are recurrent infections under the foreskin, or when
the opening to the penis is completely blocked by the
foreskin. Phimosis is a tight ring of foreskin often made
of scar tissue preventing retraction of the foreskin.
It may be primary, or secondary to recurrent infection.
It may produce urinary obstruction with ballooning of
the foreskin. Phimosis is different than having a nonretractable foreskin, which is normal in many boys.

KEY TERMS
Balanitis xerotica obliterans (BXO)—A chronic,
progressive, hardening skin inflammation of the
penis.
Buck’s fascia—The deep connective tissue of
the penis.
Circumcision—The removal of all or part of the
foreskin from the penis.
Corticosteroids—A synthetic drug similar or identical to a natural corticosteroid, used to reduce
inflammation.
Glans—The head of the penis.
Paraphimosis—The entrapment of a retracted foreskin behind the coronal sulcus, a groove that separates the shaft and head of the penis.

Treatment
If the foreskin cannot be pulled back into place
treatment should be sought. If the blood flow to the
penis is restricted then emergency treatment is
required and if the foreskin cannot be pulled back a
surgical cut to the trapped foreskin may be required.
Failure to seek treatment can result in permanent
damage to the penis. Once phimosis is diagnosed, the
available treatments include topical corticosteroids,
manual stretching, foreskin surgical repair or plastic
surgery, and circumcision. Conservative treatments
should be tried in the first instance and surgery used
as the treatment of last resort.
A number of studies show that phimosis can be
safely and effectively treated by the application of
topical steroids in 80–90% of cases. Betamethasone
cream 0.05% should be applied to the exterior and
interior of the tip of the foreskin two or three times a
day. The treatment should be discontinued as ineffective after three months if the foreskin has not become
retractile during this time.
A number of corrections are available for the adult
or adolescent non-retractable foreskin. These include
surgery to repair the foreskin, in which an incision is
made through the constrictive band of the foreskin. The
underlying tissue is spread with forceps to expose the
Buck’s fascia (the deep, connective tissue of the penis)
and the incision is closed with absorbable sutures. This
procedure has less risk of disease and infection than
circumcision, and allows the foreskin to be retained.
Circumcision is very traumatic to a child. It is
essentially irreversible and should be the treatment of
GALE ENCYCLOPEDIA OF MEDICINE

last resort. Phimosis due to balanitis xerotica obliterans (BXO), a chronic, progressive, hardening skin
inflammation of the penis, has been considered the
one common absolute indication for circumcision.

Alternative treatment
There are no alternative medicine treatments for
phimosis.

Prognosis
In most men, phimosis is not a serious problem
and will not require treatment. However, it is not
expected to improve on its own. With treatment, phimosis in most males can be managed or corrected.

Prevention
Proper hygiene is the most important preventative
measure. The American Academy of Pediatrics recommends that the immature foreskin of boys not be forced
back for cleaning. The only person who should clean
and retract the foreskin is the boy himself. Bubble bath
products and other chemical irritants can cause the
foreskin to tighten and it is recommended they should
be avoided by males with foreskins.
Resources
BOOKS

Icon Health Publications.Phimosis: A Medical Dictionary,
Bibliography, and Annotated Research Guide to Internet
References San Diego: Icon Health Publications, 2004.
2883

Phimosis

Causes & symptoms

Phlebotomy

Precautions

PERIODICALS

‘‘GP Registrar: Pictorial-Case Study (Diagnosis of
Phimosis).’’ GP (February 11, 2005): 66.
Berk, David R. ‘‘Paraphimosis in a Middle-Aged Adult
After Intercourse.’’American Family Physician
(February 15, 2004): 807.
Choe, Dr. Jong M. ‘‘Paraphimosis: Current Treatment
Options.’’American Family Physician(December 15,
2000): 2623–2627.
ORGANIZATIONS

American Foundation for Urologic Disease. 1000 Corporate
Blvd., Suite 410, Linthicum, MD 21090. (410) 689-3990
or (800) 828-7866. http://www.afud.org.
OTHER

December 19, 2004. Circumcision Information and Resource
Pages.Conservative Treatment of Phimosis: Alternatives
to Radical Circumcision <http://www.cirp.org/library/
treatment/phimosis/> (Accessed March 31, 2005).

Ken R. Wells

Phlebitis see Thrombophlebitis

Phlebotomy
Definition
Phlebotomy is the act of drawing or removing
blood from the circulatory system through a cut
(incision) or puncture in order to obtain a sample for
analysis and diagnosis. Phlebotomy is also done as
part of the patient’s treatment for certain blood
disorders.

Purpose
Treatment
Phlebotomy that is part of treatment (therapeutic
phlebotomy) is performed to treat polycythemia vera,
a condition that causes an elevated red blood cell
volume (hematocrit). Phlebotomy is also prescribed
for patients with disorders that increase the amount
of iron in their blood to dangerous levels, such as
hemochromatosis, hepatitis B, and hepatitis C.
Patients with pulmonary edema may undergo phlebotomy procedures to decrease their total blood volume.

Patients who are anemic or have a history of
cardiovascular disease may not be good candidates
for phlebotomy.

Description
Phlebotomy, which is also known as venesection,
is performed by a nurse or a technician known as a
phlebotomist. Blood is usually taken from a vein on
the back of the hand or inside of the elbow. Some
blood tests, however, may require blood from an
artery. The skin over the area is wiped with an antiseptic, and an elastic band is tied around the arm. The
band acts as a tourniquet, slowing the blood flow in
the arm and making the veins more visible. The
patient is asked to make a fist, and the technician
feels the veins in order to select an appropriate one.
When a vein is selected, the technician inserts a needle
into the vein and releases the elastic band. The appropriate amount of blood is drawn and the needle is
withdrawn from the vein. The patient’s pulse and
blood pressure may be monitored during the
procedure.
For some tests requiring very small amounts of
blood for analysis, the technician uses a finger stick.
A lance, or small needle, makes a small cut in the
surface of the fingertip, and a small amount of blood
is collected in a narrow glass tube. The fingertip may
be squeezed to get additional blood to surface.
The amount of blood drawn depends on the
purpose of the phlebotomy. Blood donors usually
contribute a unit of blood (500 mL) in a session. The
volume of blood needed for laboratory analysis varies
widely with the type of test being conducted.
Therapeutic phlebotomy removes a larger amount of
blood than donation and blood analysis require.
Phlebotomy for treatment of hemochromatosis typically involves removing a unit of blood–or 250 mg of
iron–once a week. Phlebotomy sessions are required
until iron levels return to a consistently normal level,
which may take several months to several years.
Phlebotomy for polycythemia vera removes enough
blood to keep the patient’s hematocrit below 45%.
The frequency and duration of sessions depends on
the patient’s individual needs.

Preparation
Diagnosis
Phlebotomy is also used to remove blood from the
body during blood donation and for analysis of the
substances contained within it.
2884

Patients having their blood drawn for analysis
may be asked to discontinue medications or to avoid
food (to fast) for a period of time before the blood
test. Patients donating blood will be asked for a brief
GALE ENCYCLOPEDIA OF MEDICINE

Finger stick—A technique for collecting a very
small amount of blood from the fingertip area.
Hemochromatosis—A genetic disorder known as
iron overload disease. Untreated hemochromatosis
may cause osteoporosis, arthritis, cirrhosis, heart
disease, or diabetes.

PERIODICALS

Wolfe, Yun Lee. ‘‘Case of the Ceaseless Fatigue.’’Prevention
Magazine July 1997: 88-94.

Paula Anne Ford-Martin

Thrombocytosis—A vascular condition characterized by high blood platelet counts.
Tourniquet—Any device that is used to compress a
blood vessel to stop bleeding or as part of collecting
a blood sample. Phlebotomists usually use an elastic band as a tourniquet.
Venesection—Another name for phlebotomy.

Phobias
Definition
A phobia is an intense but unrealistic fear that can
interfere with the ability to socialize, work, or go
about everyday life, brought on by an object, event
or situation.

medical history, have their blood pressure taken, and
have their hematocrit checked with a finger stick test
prior to donation.

Aftercare
After blood is drawn and the needle is removed,
pressure is placed on the puncture site with a cotton
ball to stop bleeding, and a bandage is applied. It is not
uncommon for a patient to feel dizzy or nauseated
during or after phlebotomy. The patient may be
encouraged to rest for a short period once the procedure is completed. Patients are also instructed to drink
plenty of fluids and eat regularly over the next 24
hours to replace lost blood volume. Patients who
experience swelling of the puncture site or continued
bleeding after phlebotomy should get medical help at
once.

Risks
Most patients will have a small bruise or mild
soreness at the puncture site for several days.
Therapeutic phlebotomy may cause thrombocytosis
and chronic iron deficiency (anemia) in some patients.
As with any invasive procedure, infection is also a risk.
This risk can be minimized by the use of prepackaged
sterilized equipment and careful attention to proper
technique.

Normal results
Normal results include obtaining the needed
amount of blood with the minimum of discomfort to
the patient.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Just about everyone is afraid of something—an
upcoming job interview or being alone outside after
dark. But about 18% of all Americans are tormented
by irrational fears that interfere with their daily lives.
They are not ‘‘crazy’’—they know full well their fears
are unreasonable–but they can not control the fear.
These people have phobias.
Phobias belong to a large group of mental
problems known as anxiety disorders that include
obsessive-compulsive disorder (OCD), panic disorder,
and post-traumatic stress disorder. Phobias themselves can be divided into three specific types:


specific phobias (formerly called ‘‘simple phobias’’)



social phobia



agoraphobia
Specific phobias

As its name suggests, a specific phobia is the fear
of a particular situation or object, including anything
from airplane travel to dentists. Found in one out of
every 10 Americans, specific phobias seem to run in
families and are roughly twice as likely to appear in
women. If the person rarely encounters the feared
object, the phobia does not cause much harm.
However, if the feared object or situation is common,
it can seriously disrupt everyday life. Common examples of specific phobias, which can begin at any age,
include fear of snakes, flying, dogs, escalators, elevators, high places, or open spaces.
2885

Phobias

Resources

KEY TERMS

Phobias

Social phobia
People with social phobia have deep fears of being
watched or judged by others and being embarrassed in
public. This may extend to a general fear of social
situations—or be more specific or circumscribed,
such as a fear of giving speeches or of performing
(stage fright). More rarely, people with social phobia
may have trouble using a public restroom, eating in a
restaurant, or signing their name in front of others.
Social phobia is not the same as shyness. Shy
people may feel uncomfortable with others, but they
don’t experience severe anxiety, they don’t worry
excessively about social situations beforehand, and
they don’t avoid events that make them feel selfconscious. On the other hand, people with social
phobia may not be shy–they may feel perfectly comfortable with people except in specific situations.
Social phobias may be only mildly irritating, or they
may significantly interfere with daily life. It is not
unusual for people with social phobia to turn down
job offers or avoid relationships because of their fears.
Agoraphobia
Agoraphobia is the intense fear of feeling trapped
and having a panic attack in a public place. It usually
begins between ages 15 and 35, and affects three times
as many women as men—about 3% of the population.
An episode of spontaneous panic is usually the
initial trigger for the development of agoraphobia.
After an initial panic attack, the person becomes
afraid of experiencing a second one. Patients literally
‘‘fear the fear,’’ and worry incessantly about when and
where the next attack may occur. As they begin to
avoid the places or situations in which the panic attack
occurred, their fear generalizes. Eventually the person
completely avoids public places. In severe cases,
people with agoraphobia can no longer leave their
homes for fear of experiencing a panic attack.

Causes and symptoms
Experts don’t really know why phobias develop,
although research suggests the tendency to develop
phobias may be a complex interaction between heredity
and environment. Some hypersensitive people have
unique chemical reactions in the brain that cause them
to respond much more strongly to stress. These people
also may be especially sensitive to caffeine, which triggers certain brain chemical responses.
Advances in neuroimaging have also led researchers to identify certain parts of the brain and specific
neural pathways that are associated with phobias. One
2886

part of the brain that is currently being studied is the
amygdala, an almond-shaped body of nerve cells
involved in normal fear conditioning. Another area
of the brain that appears to be linked to phobias is
the posterior cerebellum.
While experts believe the tendency to develop phobias runs in families and may be hereditary, a specific
stressful event usually triggers the development of a
specific phobia or agoraphobia. For example, someone
predisposed to develop phobias who experiences severe
turbulence during a flight might go on to develop a
phobia about flying. What scientists don’t understand
is why some people who experience a frightening or
stressful event develop a phobia and others do not.
Social phobia typically appears in childhood or
adolescence, sometimes following an upsetting or
humiliating experience. Certain vulnerable children
who have had unpleasant social experiences (such as
being rejected) or who have poor social skills may
develop social phobias. The condition also may be
related to low self-esteem, unassertive personality,
and feelings of inferiority.
A person with agoraphobia may have a panic
attack at any time, for no apparent reason. While the
attack may last only a minute or so, the person remembers the feelings of panic so strongly that the possibility
of another attack becomes terrifying. For this reason,
people with agoraphobia avoid places where they might
not be able to escape if a panic attack occurs. As the fear
of an attack escalates, the person’s world narrows.
While the specific trigger may differ, the symptoms
of different phobias are remarkably similar: e.g., feelings
of terror and impending doom, rapid heartbeat and
breathing, sweaty palms, and other features of a panic
attack. Patients may experience severe anxiety symptoms in anticipating a phobic trigger. For example,
someone who is afraid to fly may begin having episodes
of pounding heart and sweating palms at the mere
thought of getting on a plane in two weeks.

Diagnosis
A mental health professional can diagnose phobias after a detailed interview and discussion of both
mental and physical symptoms. Social phobia is often
associated with other anxiety disorders, depression, or
substance abuse.

Treatment
People who have a specific phobia that is easy to
avoid (such as snakes) and that doesn’t interfere with
their lives may not need to get help. When phobias do
GALE ENCYCLOPEDIA OF MEDICINE

Medication can block the feelings of panic, and
when combined with cognitive-behavioral therapy, can
be quite effective in reducing specific phobias and
agoraphobia.
Cognitive-behavioral therapy adds a cognitive
approach to more traditional behavioral therapy.
It teaches patients how to change their thoughts,
behavior, and attitudes, while providing techniques
to lessen anxiety, such as deep breathing, muscle
relaxation, and refocusing.
One cognitive-behavioral therapy is desensitization
(also known as exposure therapy), in which people are
gradually exposed to the frightening object or event
until they become used to it and their physical symptoms decrease. For example, someone who is afraid of
snakes might first be shown a photo of a snake. Once
the person can look at a photo without anxiety, he
might then be shown a video of a snake. Each step is
repeated until the symptoms of fear (such as pounding
heart and sweating palms) disappear. Eventually, the
person might reach the point where he can actually
touch a live snake. Three fourths of patients are significantly improved with this type of treatment.
Another more dramatic cognitive-behavioral
approach is called flooding. It exposes the person
immediately to the feared object or situation. The
person remains in the situation until the anxiety lessens.
Several drugs are used to treat specific phobias by
controlling symptoms and helping to prevent panic
attacks. These include anti-anxiety drugs (benzodiazepines) such as alprazolam (Xanax) or diazepam
(Valium). Blood pressure medications called beta
blockers, such as propranolol (Inderal) and atenolol
(Tenormin), appear to work well in the treatment of
circumscribed social phobia, when anxiety gets in the
way of performance, such as public speaking. These
drugs reduce overstimulation, thereby controlling the
physical symptoms of anxiety.
In addition, some antidepressants may be effective
when used together with cognitive-behavioral therapy.
These include the monoamine oxidase inhibitors
(MAO inhibitors) phenelzine (Nardil) and tranylcypromine (Parnate), as well as selective serotonin reuptake
inhibitors (SSRIs) like fluoxetine (Prozac), paroxetine
(Paxil), sertraline (Zoloft) and fluvoxamine (Luvox).
GALE ENCYCLOPEDIA OF MEDICINE

A medication that shows promise as a treatment
for social phobia is valproic acid (Depakene or
Depakote), which is usually prescribed to treat seizures
or to prevent migraine headaches. Researchers conducting a twelve-week trial with 17 patients found
that about half the patients experienced a significant
improvement in their social anxiety symptoms while
taking the medication. Further studies are underway.
In all types of phobias, symptoms may be eased by
lifestyle changes, such as:


eliminating caffeine



cutting down on alcohol



eating a good diet



getting plenty of exercise



reducing stress

Treating agoraphobia is more difficult than other
phobias because there are often so many fears
involved, such as open spaces, traffic, elevators, and
escalators. Treatment includes cognitive-behavioral
therapy with antidepressants or anti-anxiety drugs.
Paxil and Zoloft are used to treat panic disorders
with or without agoraphobia.

Prognosis
Phobias are among the most treatable mental
health problems; depending on the severity of the
condition and the type of phobia, most properly treated patients can go on to lead normal lives. Research
suggests that once a person overcomes the phobia, the
problem may not return for many years—if at all.
Untreated phobias are another matter. Only
about 20% of specific phobias will go away without
treatment, and agoraphobia will get worse with time if
untreated. Social phobias tend to be chronic, and will
not likely go away without treatment. Moreover,
untreated phobias can lead to other problems, including depression, alcoholism, and feelings of shame and
low self-esteem.
A group of researchers in Boston reported in 2003
that phobic anxiety appears to be a risk factor for
Parkinson’s disease (PD) in males, although it is not
yet known whether phobias cause PD or simply share
an underlying biological cause.
While most specific phobias appear in childhood
and subsequently fade away, those that remain in
adulthood often need to be treated. Unfortunately,
most people never get the help they need; only about
25% of people with phobias ever seek help to deal with
their condition.
2887

Phobias

interfere with a person’s daily life, a combination of
psychotherapy and medication can be quite effective.
While most health insurance covers some form of
mental health care, most do not cover outpatient
care completely, and most have a yearly or lifetime
maximum.

Phosphorus imbalance

KEY TERMS
Agoraphobia—An intense fear of being trapped in
a crowded, open, or public space where it may be
hard to escape, combined with the dread of having
a panic attack.
Benzodiazepine—A class of drugs that have a
hypnotic and sedative action, used mainly as
tranquilizers to control symptoms of anxiety.
Beta blockers—A group of drugs that are usually
prescribed to treat heart conditions, but that also
are used to reduce the physical symptoms of anxiety
and phobias, such as sweating and palpitations.
Monoamine oxidase inhibitors (MAO inhibitors)—
A class of antidepressants used to treat social
phobia.
Neuroimaging—The use of x ray studies and
magnetic resonance imaging (MRIs) to detect
abnormalities or trace pathways of nerve activity
in the central nervous system.
Selective serotonin reuptake inhibitors (SSRIs)—A
class of antidepressants that work by blocking the
reabsorption of serotonin in the brain, raising the
levels of serotonin. SSRIs include Prozac, Zoloft,
and Paxil.
Serotonin—One of three major types of neurotransmitters found in the brain that is linked to
emotions.
Social phobia—Fear of being judged or ridiculed
by others; fear of being embarrassed in public.

Prevention
There is no known way to prevent the development of phobias. Medication and cognitive-behavioral
therapy may help prevent the recurrence of symptoms
once they have been diagnosed.
Resources

International Clinical Psychopharmacology 18 (May
2003): 169–172.
Ploghaus, A., L. Becerra, C. Borras, and D. Borsook.
‘‘Neural Circuitry Underlying Pain Modulation:
Expectation, Hypnosis, Placebo.’’ Trends in Cognitive
Science 7 (May 2003): 197–200.
Rauch, S. L., L. M. Shin, and C. I. Wright. ‘‘Neuroimaging
Studies of Amygdala Function in Anxiety Disorders.’’
Annals of the New York Academy of Sciences 985
(April 2003): 389–410.
Weisskopf, M. G., H. Chen, M. A. Schwarzschild, et al.
‘‘Prospective Study of Phobic Anxiety and Risk of
Parkinson’s Disease.’’ Movement Disorders 18 (June
2003): 646–651.
ORGANIZATIONS

Agoraphobics Building Independent Lives. 1418 Lorraine
Ave., Richmond, VA 23227.
Agoraphobics In Motion. 605 W. 11 Mile Rd., Royal Oak,
MI 48067.
American Psychiatric Association (APA). 1400 K Street,
NW, Washington, DC 20005. (888) 357-7924. <http://
www.psych.org>.
Anxiety Disorders Association of America. 11900 Parklawn
Dr., Ste. 100, Rockville, MD 20852. (301) 231-9350.
National Anxiety Foundation. 3135 Custer Dr., Lexington,
KY 40517. (606) 272-7166. <http://www.lexington-online.com/naf.html>.
National Institute of Mental Health (NIMH) Office
of Communications. 6001 Executive Boulevard,
Room 8184, MSC 9663, Bethesda, MD 20892-9663.
(866) 615-NIMH or (301) 443-4513. <http://
www.nimh.nih.gov>.
OTHER

Anxiety Network Homepage. <http://www.anxietynetwork.
com>.
National Institute of Mental Health (NIMH). Anxiety
Disorders. NIH Publication No. 02-3879. Bethesda,
MD: NIMH, 2002.

Carol A. Turkington
Rebecca J. Frey, PhD

Phospholipidosis see Pulmonary alveolar
proteinosis

BOOKS

American Psychiatric Association.Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised. Washington,
DC: American Psychiatric Association, 2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Phobic Disorders.’’ In The Merck Manual of Diagnosis
and Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Kinrys, G., M. H. Pollack, N. M. Simon, et al. ‘‘Valproic
Acid for the Treatment of Social Anxiety Disorder.’’
2888

Phosphorus imbalance
Definition
Phosphorus imbalance refers to conditions in
which the element phosphorus is present in the body
at too high a level (hyperphosphatemia) or too low a
level (hypophosphatemia).
GALE ENCYCLOPEDIA OF MEDICINE

Almost all of the phosphorus in the body occurs
as phosphate (phosphorus combined with four oxygen
atoms), and most of the body’s phosphate (85%) is
located in the skeletal system, where it combines with
calcium to give bones their hardness. The remaining
amount (15%) exists in the cells of the body, where it
plays an important role in the formation of key nucleic
acids, such as DNA, and in the process by which the
body turns food into energy (metabolism). The body
regulates phosphate levels in the blood through the
controlled release of parathyroid hormone (PTH)
from the parathyroid gland and calcitonin from the
thyroid gland. PTH keeps phosphate levels from
becoming too high by stimulating the excretion of
phosphate in urine and causing the release of calcium
from bones (phosphate blood levels are inversely
proportional to calcium blood levels). Calcitonin
keeps phosphate blood levels in check by moving
phosphates out of the blood and into the bone matrix
to form a mineral salt with calcium.
Most phosphorus imbalances develop gradually
and are the result of other conditions or disorders,
such as malnutrition, poor kidney function, or a
malfunctioning gland.

Causes and symptoms
Hypophosphatemia
Hypophosphatemia (low blood phosphate) has
various causes. Hyperparathyroidism, a condition in
which the parathyroid gland produces too much PTH,
is one primary cause. Poor kidney function, in which
the renal tubules do not adequately reabsorb phosphorus, can result in hypophosphatemia, as can overuse of diuretics, such as theophylline, and antacids
containing aluminum hydroxide. Problems involving
the intestinal absorption of phosphate, such as chronic
diarrhea or a deficiency of vitamin D (needed by the
intestines to properly absorb phosphates) can cause the
condition. Malnutrition due to chronic alcoholism can
result in an inadequate intake of phosphorus. Recovery
from conditions such as diabetic ketoacidosis or severe
burns can provoke hypophosphatemia, since the body
must use larger-than-normal amounts of phosphate.
Respiratory alkylosis, brought on by hyperventilation,
can also result in temporary hypophosphatemia.
Symptoms generally occur only when phosphate
levels have decreased profoundly. They include muscle
weakness, tingling sensations, tremors, and bone
weakness. Hypophosphatemia may also result in confusion and memory loss, seizures, and coma.
GALE ENCYCLOPEDIA OF MEDICINE

Hyperphosphatemia
Hyperphosphatemia (high blood phosphate)
also has various causes. It is most often caused by a
decline in the normal excretion of phosphate in urine
as a result of kidney failure or impaired function.
Hypoparathyroidism, a condition in which the parathyroid gland does not produce enough PTH, or pseudoparathyroidism, a condition in which the kidneys
lose their ability to respond to PTH, can also contribute
to decreased phosphate excretion. Hyperphosphatemia
can also result from the overuse of laxatives or enemas
that contain phosphate. Hypocalcemia (abnormally
low blood calcium) can cause phosphate blood levels
to increase abnormally. A side-effect of hyperphosphatemia is the formation of calcium-phosphate crystals in
the blood and soft tissue.
Hyperphosphatemia is generally asymptomatic;
however, it can occur in conjunction with hypocalcemia, the symptoms of which are numbness and tingling
in the extemities, muscle cramps and spasms, depression, memory loss, and convulsions. When calciumphosphate crystals build up in the blood vessels, they
can cause arteriosclerosis, which can lead to heart
attacks or strokes. When the crystals build up in the
skin, they can cause severe itching.

Diagnosis
Disorders of phosphate metabolism are assessed
by measuring serum or plasma levels of phosphate and
calcium. Hypophosphatemia is diagnosed if the blood
phosphate level is less than 2.5 milligrams per deciliter
of blood. Hyperphosphatemia is diagnosed if the
blood phosphate level is above 4.5 milligrams per
deciliter of blood. Appropriate tests are also used to
determine if the underlying cause of the imbalance,
including assessments of kidney function, dietary
intake, and appropriate hormone levels.

Treatment
Treatment of phosphorus imbalances focuses on
correcting the underlying cause of the imbalance and
restoring equilibrium. Treating the underlying condition may involve surgical removal of the parathyroid
gland in the case of hypophosphatemia caused by
hyperparathyroidism; initiating hormone therapy in
cases of hyperphosphatemia caused by hypoparathyroidism; ceasing intake of drugs or medications that
contribute to phosphorus imbalance; or instigating
measures to restore proper kidney function.
Restoring phosphorus equilibrium in cases of mild
hypophosphatemia may include drinking a prescribed
2889

Phosphorus imbalance

Description

Photorefractive keratectomy and laser-assisted in-situ keratomileusis

solution that is rich in phosphorus; however, since this
solution can cause diarrhea, many doctors recommend
that patients drink 1 qt (0.9 L) of skim milk per day
instead, since milk and other diary products are significant sources of phosphate. Other phosphate-rich foods
include green, leafy vegetables; peas and beans; nuts;
chocolate; beef liver; turkey; and some cola drinks.
Severe hypophosphatemia may be treated with the
administration of an intravenous solution containing
phosphate.
Restoring phosphorus equilibrium in cases of
mild hyperphosphatemia involves restricting intake
of phosphorus-rich foods and taking a calcium-based
antacid that binds to the phosphate and blocks its
absorption in the intestines. In cases of severe hyperphosphatemia, an intravenous infusion of calcium
gluconate may be administered. Dialysis may also be
required in severe cases to help remove excess phosphate from the blood.

Prognosis
The prognosis for treating hyperphosphatemia
and hypophosphatemia are excellent, though in cases
where these problems are due to genetic disease, lifelong hormone treatment may be necessary.

Prevention
Phosphorus imbalances caused by hormonal
disorders or other genetically determined conditions
cannot be prevented. Hypophosphatemia resulting
from poor dietary intake can be prevented by eating
foods rich in phosphates, and hypophosphatemia
caused by overuse of diuretics or antacids can be prevented by strictly following instructions concerning
proper dosages, as can hyperphosphatemia due to
excessive use of enemas or laxative. Finally, patients on
dialysis or who are being fed intravenously should be
monitored closely to prevent phosphorus imbalances.
Resources
PERIODICALS

Barcia, J. P., C. F. Strife, and C. B. Langman. ‘‘Infantile
Hypophosphatemia: Treatment Options to Control
Hypercalcemia, Hypercalciuria, and ChronicBone
Demineralization.’’ Journal of Pediatrics 130 (1997):
825-828.

Tom Brody, PhD

Photoallergy see Photosensitivity
Photokeratitis see Keratitis
2890

Photorefractive keratectomy
and laser-assisted in-situ
keratomileusis
Definition
Photorefractive keratectomy (PRK) and laserassisted in-situ keratomileusis (LASIK) are two similar surgical techniques that use an excimer laser to
correct nearsightedness (myopia) by reshaping the
cornea. The cornea is the clear outer structure of the
eye that lies in front of the colored part of the eye (iris).
PRK and LASIK are two forms of vision-correcting
(refractive) surgery. The two techniques differ in how
the surface layer of the cornea is treated. As of mid
1998, two eximer lasers (Summit and Visx) had been
approved for laser vision correction (refractive surgery
using a laser) in the PRK procedure. Since then, Visx,
Summit, and other lasers have received approval by
the Food and Drug Administration (FDA) for use in
LASIK procedures.

Purpose
The purpose of both LASIK and PRK is to
correct nearsightedness in persons who don’t want
to, or can’t, wear eye glasses or contact lenses. Most
patients are able to see well enough to pass a driver’s
license exam without glasses or contact lenses after the
operation. After approximately age 40, the lens in the
eye stiffens making it harder to focus up close. Because
laser vision correction only affects the cornea, the procedures do not eliminate the need for reading glasses.
Patients should be wary of any ads that ‘‘guarantee’’
20/20 vision. Patients should also make sure that the
laser being used is approved by the FDA.

Precautions
Patients should be over 18 years of age, have
healthy corneas, and have vision that has been stable
for the past year. People who may not be good candidates for these procedures are pregnant women or
women who are breastfeeding (vision may not be
stable); people with scarred corneas or macular disease;
people with autoimmune diseases (i.e., systemic lupus
erythematosus or rheumatoid arthritis); or people with
diabetes. Patients with glaucoma should not have
LASIK because the intraocular pressure (IOP) of the
eye is raised during the procedure. A patient with persistent lid infections (i.e., blepharitis) may not be a good
candidate because of an increased risk of infection.
An ophthalmologist who specializes in laser vision
correction can determine who would be likely to
GALE ENCYCLOPEDIA OF MEDICINE

If a patient is thinking of having cataract surgery,
they should discuss it with the doctor. During cataract
surgery an intracocular lens (IOL) will be inserted and
that alone may correct distance vision.

Description
PRK and LASIK are both performed with an
excimer laser, which uses a cold beam of ultraviolet
light to sculpt or reshape the cornea so that light will
focus properly on the retina. The cornea is the major
focusing structure of the eye. The retina sends the
image focused on it to the brain. In myopia, the cornea
is either too steep or the eye is too long for a clear
image to be focused on the retina. PRK and LASIK
flatten out the cornea so that the image will focus more
precisely on the retina.
In PRK, the surface of the cornea is removed by
the laser. In LASIK, the outer layer of the cornea is
sliced, lifted, moved aside while the cornea is reshaped
with the laser, then replaced to speed healing. Both
procedures cause the cornea to become flatter, which
corrects the nearsighted vision.
At least one laser has been approved to treat mild
astigmatism as of 2000. Correcting farsightedness
(hyperopia) may be possible in the future.
These laser vision-correcting procedures are
rapidly replacing radial keratotomy (RK), an earlier
form of refractive surgery that involved cutting the
cornea with a scalpel in a pattern of radiating spokes.
RK has declined in popularity since the approval of the
excimer laser in 1995, falling from a high of 250,000
procedures performed per year in 1994 to 50,000 in
1997.
For both LASIK and PRK, the patient’s eye is
numbed with anesthetic drops. No injections are
necessary. The patient is awake and relaxed during
the procedure.
LASIK is sometimes referred to as a ‘‘flap and
zap’’ procedure because a thin flap of tissue is
temporarily removed from the surface of the cornea
and the underlying cornea is then ‘‘zapped’’ with a
laser. Prior to the surgery, the surface of the cornea
is marked with a dye marker so that the flap of cornea
can be precisely aligned when it is replaced. The doctor
places a suction ring on the eye to hold it steady.
During this part of the operation, which lasts only a
few seconds, the patient is not able to see. A surgical
instrument called a microkeratome is passed over the
GALE ENCYCLOPEDIA OF MEDICINE

cornea to create a very thin flap of tissue. The IOP is
increased at this time which is why it is contraindicated
in patients with glaucoma. This thin tissue layer is
folded back. The cornea is reshaped with the laser
beam and the cell layer is replaced. Because the cell
layer is not permanently removed, patients have a
faster recovery time and experience far less discomfort
than with PRK. An antibiotic drop is put in and the
eye is patched until the following day’s checkup.
In PRK, a small area of the surface layer of the
cornea is vaporized. It takes about three days for the
surface cells to grow back and vision will be blurred.
Some patients describe it as ‘‘looking through Vaseline.’’
PRK is generally recommended for patient’s with mild
to moderate myopia (usually under -5.00 diopters).
With both PRK and LASIK, there is a loud
tapping sound from the laser and a burning smell as
the cornea is reshaped. The surgery itself is painless
and takes only a minute or two. Patients are usually
able to return home immediately after surgery. Most
patients wait (up to six months) before they have the
second one done. This allows the first eye to heal and
to see if there were complications from the surgery.
The cost of these procedures can vary with geographic area and the doctor. In general, the procedure
costs $1,350–$2,500 per eye for PRK and about $500
more per eye for LASIK. PRK and LASIK are generally not covered by insurance. However, insurance
may cover these procedures for people in certain occupations, such as police officers and firefighters.

Preparation
If a patient wears contact lenses, they should not
be worn for a few weeks prior to surgery. It also is
important to discontinue contact lens wear prior to the
visual exams to make sure vision is stable. The doctor
should be advised of contact lens wear.
Upon arrival at the doctor’s office on the day
of surgery, patients are given some eye drops and a
sedative, such as Valium, to relax them. Their vision is
tested. They rest while waiting for the sedative to take
effect. Immediately before the surgery, patients are
given local anesthetic eye drops.

Aftercare
After surgery, antibiotic drops are placed in the
eye and the eye may be patched. The patient returns
for a follow-up visit the next day. The patient is usually
given a prescription for eyedrops (usually antibiotic
and anti-inflammatory). Patients who have had PRK
usually feel mild discomfort for one to three days after
2891

Photorefractive keratectomy and laser-assisted in-situ keratomileusis

benefit from the operation and suggest which of the
two operations might be more appropriate for any
given patient.

Photorefractive keratectomy and laser-assisted in-situ keratomileusis

the procedure. They may need a bandage contact lens.
Patients who have had LASIK generally have less, or
even no discomfort after the surgery. After LASIK,
antibiotic and anti-inflammatory drops are generally
necessary for one week. After PRK, steroidal eye
drops may be necessary for months. Because steroids
may increase the possibility of glaucoma or cataracts,
it is a big drawback to the procedure. The patient
should speak with the doctor to see how long followup medications will be necessary.

Blepharitits— An inflammation of the eyelid.
Cataract—A condition in which the lens of the eye
turns cloudy and interferes with vision.

Most patients return to work within one to three
days after the procedure, although visual recovery
from PRK may take as long as four weeks. An eye
shield may be used for about one week at night and
patients may be sensitive to bright light for a few days.
Patients may be asked by their doctor to keep water
out of their eye for a week and to avoid mascara or
eyeliner during this period.

Excimer laser—An instrument that is used to vaporize tissue with a cold, coherent beam of light with a
single wavelength in the ultraviolet range.

Risks

KEY TERMS

Cornea—The clear, curved tissue layer in front of
the eye. It lies in front of the colored part of the eye
(iris) and the black hole in the center of the iris
(pupil).
Diopter (D)—A unit of measure of the power or
strength of a lens.

Intraocular lens (IOL) implant—A small, plastic
device (IOL) that is usually implanted in the lens
capsule of the eye to correct vision after the lens of
the eye is removed. This is the implant is used in
cataract surgery.

There is a risk of under- or over-correction with
either of these procedures. If vision is under-corrected,
a second procedure can be performed to achieve
results that may be closer to 20/20 vision. About
5–10% of PRK patients return for an adjustment, as
do 10–25% of LASIK patients. People with higher
degrees of myopia have vision that is harder to correct
and usually have LASIK surgery rather than PRK.
This may account for the higher incidence of adjustments for LASIK patients. Patients with very high
myopia (over -15.00 diopters) may experience
improvement after LASIK, but they are not likely to
achieve 20/40 vision without glasses. However, their
glasses will not need to be as thick or heavy after the
surgery. However, most patients, especially those with
less extreme myopia, do not need glasses after the
surgery.

Macular degeneration—A condition usually associated with age in which the area of the retina
called the macula is impaired due to hardening of
the arteries (arteriosclerosis). This condition interferes with vision.
Microkeratome—A precision surgical instrument
that can slice an extremely thin layer of tissue
from the surface of the cornea.
Myopia—A vision problem in which distant objects
appear blurry. Myopia results when the cornea
is too steep or the eye is too long and the light
doesn’t focus properly on the retina. People who
are myopic or nearsighted can usually see near
objects clearly, but not far objects.
Refractive surgery—A surgical procedure that
corrects visual defects.

Haze is another possible side effect. Although
hazy vision is unlikely, it is more likely to occur after
PRK than after LASIK. This haze usually clears up.
Corneal scarring, halos, or glare at night, or an irritating bump on the cornea are other possible side effects.
As with any eye surgery, infection is possible, but rare.
Loss of vision is possible with these procedures, but
this complication is extremely rare.

Retina—The sensory tissue in the back of the eye
that is responsible for collecting visual images and
sending them to the brain.

Most complications from LASIK are related to
the creation and realignment of the flap. The microkeratome must be in good-working order and sharp.
LASIK requires a great deal of skill on the part of the
surgeon and the complication rate is related to the
experience level of the surgeon. In one study, the rate
of LASIK complications declined from 3% for
2892

surgeons during their first three months using this
technique, to 1% after a year’s experience in the technique, to 0% after 18 months experience.

Normal results
Most patients experience improvement in their
vision immediately after the operation and about
half of LASIK patients are able to see 20/30 within
one day of the surgery. Vision tends to become sharper
GALE ENCYCLOPEDIA OF MEDICINE

LASIK is more complicated than PRK because of
the addition of the microkeratome procedure.
However, LASIK generally has faster recovery time,
less pain, and less chance of halos and scarring than
PRK. LASIK can treat higher degrees of myopia
(-5.00–25.00 diopters). LASIK also requires less use
of steroids. Patients need to speak with qualified,
experienced eye surgeons to help in choosing the
procedure that is right for them.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Society of Cataract and Refractive Surgery. 4000
Legato Road, Suite 850, Fairfax, VA 22033-4055. (703)
591-2220. <http://www.ascrs.org>.

Photosensitivity

over the next few days and then stabilizes; however, it
is possible to have shifts in myopia for the next few
months. Vision clears and stabilizes faster after
LASIK than after PRK. Final vision is achieved
within three to six months with LASIK and six to
eight months with PRK. The vast majority of patients
(95% for people with low to moderate myopia and
75% for people with high levels of myopia) are able
to see 20/40 after either of these procedures and are
able to pass a driver’s license test without glasses or
contact lenses.

A skin rash on the front of a woman’s neck caused by a photosensitive reaction to sunlight. (Photograph by Dr. P. Marazzi,
Photo Researchers, Inc. Reproduced by permission.)

Causes and symptoms
There are over three dozen diseases, two dozen
drugs, a variety of herbal preparations, and several
perfume and cosmetic components that can cause
photosensitivity. There are also several different
types of reaction to sunlight—phototoxicity, photoallergy, and polymorphous light eruption. In addition,
prolonged exposure to sunlight, even in normal skin,
leads to skin aging and cancer. These effects are
accelerated in patients who have photosensitivity.


Phototoxicity is a severely exaggerated reaction to sunlight caused by a new chemical in the skin. The primary
symptom is sunburn, which is rapid and can be severe
enough to blister (a second degree burn). The chemicals
associated with phototoxicity are usually drugs. The
list includes several common antibiotics—quinolones,
sulfonamides, and tetracyclines; diuretics (water pills);
major tranquilizers; oral diabetes medication; and
cancer medicines. There are also some dermatologic
drugs, both topical and oral, that can sensitize skin.



Photoallergy produces an intense itching rash on
exposure to sunlight. Patients develop chronic skin
changes (lichen simplex) as a result of scratching.
Some of the agents that cause phototoxicity can also
cause photoallergy. Some cosmetic and perfume
ingredients, including a compound that was formerly
used in sunscreens—para-amino benzoic acid
(PABA)—can do this. Most sunscreen preparations
in the early 2000s, however, no longer include PABA.



Polymorphous light eruption (PLE) resembles photoallergy in its production of intensely itching rashes in
sunlight. However, this condition lessens with continued light exposure, and so is seen mostly in the spring.
Also, there does not seem to be an identifiable
chemical involved. PLE is most likely to develop in

Louann W. Murray, PhD

Photosensitivity
Definition
Photosensitivity refers to any increase in the reactivity of the skin to sunlight.

Description
The skin is a carefully designed interface between
our bodies and the outside world. It is infection-proof
when intact, nearly waterproof, and filled with protective mechanisms. Sunlight threatens the health of
the skin. Normal skin is highly variable in its ability
to resist sun damage. Natural skin pigmentation is
its main protection. The term photosensitivity refers
to any increase beyond what is considered normal
variation.
GALE ENCYCLOPEDIA OF MEDICINE

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Photosensitivity

fair-skinned individuals. It is estimated to affect
about 10% of the United States population compared
to 21% of the Swedish population. The female: male
ratio is 2.5: 1, but it is thought that the imbalance may
be due to the fact that women are more likely than
men to seek treatment for PLE.


There is a form of inherited PLE that affects Native
Americans. The inheritance pattern is autosomal
dominant.
Diseases of several kinds increase skin sensitivity:



A hereditary disease called xeroderma pigmentosum
includes a defect in repair mechanisms that greatly
accelerates skin damage from sunlight.



A family of metabolic diseases called porphyrias produce chemicals (porphyrins) that absorb sunlight in
the skin and thereby cause damage.



Albinos lack skin pigment through a genetic defect
and are thus very sensitive to light.

KEY TERMS



Malnutrition, specifically a deficiency of niacin
known as pellagra, sensitizes the skin.



Several diseases like acne, systemic lupus erythematosus, rosacea, and herpes simplex (fever blisters)
decrease the resistance of the skin to sun damage.
Rosacea is sometimes described as a photoaggravated skin disorder because its symptoms increase
in severity when patients are exposed to sunlight.

Albino—A person or animal lacking normal coloring in the eyes, hair, and skin due to a hereditary
inability to produce the skin pigment melanin. The
condition itself is called albinism.



Photosensitivity is increasingly recognized as a common development in HIV-positive patients. Risk factors for photosensitivity in this group include
African American ethnicity and treatment with
highly active antiretroviral therapy (HAART).

Diagnosis
The pattern of appearance on the skin, a history of
drug or chemical exposure, and the timing of the
symptoms often suggests a diagnosis. A skin biopsy
may be needed for further clarification.

Treatment
Removal of the offending drug or chemical is primary. Direct sunlight exposure should be limited. Some
people must avoid sunlight altogether, while others can
tolerate some direct sunlight with the aid of sunscreens.

Prevention
A sunscreen with an SPF of 15 or greater protects
most skin from damage. Such protective garments as
hats and long-sleeved shirts are highly recommended
in addition.
2894

This person had a photoxic reaction after taking an antibiotic
drug. (Photo Researchers, Inc. Reproduced by permission.)

Biopsy—Surgical removal of tissue for examination.
Rosacea—A chronic skin disease characterized by
persistent redness of the skin and periodic outbreaks of pustules, usually affecting the middle
third of the face.

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Pigmentation Disorders.’’ Section 10, Chapter 123 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Reactions to Sunlight.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Bilu, D., A. J. Mamelak, R. H. Nguyen, et al. ‘‘Clinical and
Epidemiologic Characterization of Photosensitivity in
HIV-Positive Individuals.’’ Photodermatology,
Photoimmunology and Photomedicine 20 (August 2004):
175–183.
Ciocon, J. O., D. G. Ciocon, and D. J. Galindo. ‘‘Dietary
Supplements in Primary Care. Botanicals Can Affect
Surgical Outcomes and Follow-Up.’’ Geriatrics 59
(September 2004): 20–24.
GALE ENCYCLOPEDIA OF MEDICINE

emitted by the light boxes used in phototherapy,
patients taking photosensitizing medications (medications making the skin more sensitive to light) and
those who have sun-sensitive skin should consult
with their physician before beginning treatment.
Patients with medical conditions that make them
sensitive to ultraviolet rays should also be seen by a
physician before starting phototherapy. Patients who
have a history of mood swings or mania should be
monitored closely, since phototherapy may cause
excessive mood elevation in some individuals.

Description

ORGANIZATIONS

American Academy of Dermatology (AAD). P. O. Box
4014, Schaumburg, IL 60168-4014. (847) 330-0230.
<http://www.aad.org>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <http://www.fda.gov>.

J. Ricker Polsdorfer, MD
Rebecca J. Frey, PhD

Phototherapy
Definition
Phototherapy, or light therapy, is the administration of doses of bright light in order to normalize the
body’s internal clock and/or relieve depression.

Purpose
Phototherapy is prescribed primarily to treat
seasonal affective disorder (SAD), a mood disorder
characterized by depression in the winter months,
and is occasionally employed to treat insomnia and
jet lag. The exact mechanisms by which the treatment
works are not known, but the bright light employed in
phototherapy may act to readjust the body’s circadian
(daily) rhythms, or internal clock. Other popular
theories are that light triggers the production of serotonin, a neurotransmitter believed to be related to
depressive disorders, or that it influences the body’s
production of melatonin, a hormone derived from
serotonin that may be related to circadian rhythms.

Precautions
Patients with eye problems should see an
ophthalmologist regularly, both before and during
phototherapy. Because some ultraviolet rays are
GALE ENCYCLOPEDIA OF MEDICINE

Phototherapy is generally administered at home.
The most commonly used phototherapy equipment is
a portable lighting device known as a light box. The
box may be mounted upright to a wall, or slanted
downwards towards a table. The patient sits in front
of the box for a prescribed period of time (anywhere
from 15 minutes to several hours). Some patients with
SAD undergo phototherapy sessions two or three
times a day, others only once. The time of day and
number of times treatment is administered depend
on the physical needs and lifestyle of the individual
patient. If phototherapy has been prescribed for the
treatment of SAD, it typically begins in the fall months
as the days begin to shorten, and continues throughout the winter and possibly the early spring.
The light from a slanted light box is designed to
focus on the table it sits upon, so patients may look
down to read or do other sedentary activities during
therapy. Patients using an upright light box must face
the light source (although they need not look directly
into the light). The light sources in these light boxes
typically range from 2,500–10,000 lux. (In contrast,
average indoor lighting is 300–500 lux; a sunny
summer day is about 100,000 lux).
Phototherapy prescribed for the treatment of SAD
may be covered by insurance. Individuals requiring
phototherapy should check with their insurance company to see if the cost of renting or purchasing a light
box is covered.

Aftercare
Patients beginning light therapy for SAD may
need to adjust the length, frequency, and timing of
their phototherapy sessions to achieve the maximum
benefit. These patients should keep their doctor
informed of their progress and the status of their
depressive symptoms. Occasionally, antidepressants
and/or psychotherapy may be recommended as an
adjunct to phototherapy.
2895

Phototherapy

Levy, Stanley B., MD. ‘‘Sunscreens and Photoprotection.’’
eMedicine November 25, 2002. <http://www.emedicine.
com/derm/topic510.htm>.
Murphy, G. ‘‘Ultraviolet Light and Rosacea.’’ Cutis 74,
Supplement 3 (September 2004): 13–16, 32–34.
Palmer, R. A., C. B. van de Pas, E. Campalani, et al.
‘‘A Simple Method to Assess Severity of Polymorphic
Light Eruption.’’ British Journal of Dermatology 151
(September 2004): 645–652.
Shirin, Sophie, MD, Raul DelRosario, MD, and Ada
Winkielman, MD. ‘‘Polymorphous Light Eruption.’’
eMedicine October 16, 2003. <http://www.emedicine.
com/derm/topic342.htm>.

Physical allergy

KEY TERMS
Circadian rhythm—The rhythmic repetition of
certain phenomena in living organisms at about
the same time each day.
Lux—A standard unit of measure for illumination.
Neurotransmitter—A chemical in the brain that
transmits messages between neurons, or nerve cells.
Photosensitivity—An abnormally heightened
reaction to light.
Seasonal affective disorder (SAD)—A mood disorder characterized by depression during the winter
months. An estimated 11 million Americans experience SAD.

Risks
An abnormally elevated or expansive mood
(hypomania) may occur, but it is usually temporary.
Some patients undergoing phototherapy treatment
report side effects of eyestrain, headaches, insomnia,
fatigue, sunburn, and dry eyes or nose. Most of these
effects can be managed by adjusting the timing and
duration of the phototherapy sessions. A strong sun
block and eye and nose drops can alleviate the other
problems. Long-term studies have shown no negative
effects to the eye function of individuals undergoing
phototherapy treatments.

Physical allergy
Definition
Physical allergies are allergic reactions to cold,
sunlight, heat, or minor injury.

Description
The immune system is designed to protect the body
from harmful invaders such as germs. Occasionally, it
goes awry and attacks harmless or mildly noxious
agents, doing more harm than good. This event is
termed allergy if the target is from the outside—like
pollen or bee venom—and autoimmunity if it is caused
by one of the body’s own components.
The immune system usually responds only to certain kinds of chemicals, namely proteins. However,
non-proteins can trigger the same sort of response,
probably by altering a protein to make it look like a
target. Physical allergy refers to reactions in which a
protein is not the initial inciting agent.
Sometimes it takes a combination of elements to
produce an allergic reaction. A classic example is
drugs that are capable of sensitizing the skin to sunlight. The result is phototoxicity, which appears as an
increased sensitivity to sunlight or as localized skin
rashes on sun-exposed areas.

Causes and symptoms


Minor injury, such as scratching, causes itchy welts to
develop in about 5% of people. The presence of itchy
welts (urticaria) is a condition called dermographism.



Cold can change certain proteins in the blood so that
they induce an immune reaction. This may indicate
that there are abnormal proteins in the blood from a
disease of the bone marrow. The reaction may also
involve the lungs and circulation, producing wheezing
and fainting.



Heat allergies can be caused by exercise or even
strong emotions in sensitive people.



Sunlight, even without drugs, causes immediate
urticaria in some people. This may be a symptom of
porphyria—a genetic metabolic defect.



Elements like nickel and chromium, although not
proteins, commonly cause skin rashes, and iodine
allergy causes skin rashes and sores in the mouth in
allergic individuals.



Pressure or vibration can also cause urticaria.



Water contact can cause aquagenic urticaria, presumably due to chlorine or some other trace chemical

Normal results
Patients with SAD typically report an alleviation
of depressive symptoms within two to 14 days after
beginning phototherapy.
Resources
ORGANIZATIONS

National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.
Society for Light Treatment and Biological Rhythms. P.O.
Box 591687, 174 Cook St., San Francisco, CA 941591687. <http://www.websciences.org/sltbr>.

Paula Anne Ford-Martin

Phototoxic reaction see Photosensitivity
Phycomycosis see Mucormycosis
2896

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Antihistamine—Drugs that block histamine, a
major cause of itching.
Hemolysis—Destruction of red blood cells.
Inflammation—Heat, redness, swelling, and pain
caused by an immune response.

in the water, although distilled water has been known
to cause this reaction.
When the inflammatory reaction involves deeper
layers of the skin, urticaria becomes angioedema. The
skin, especially the lips and eyelids, swells. The tongue,
throat, and parts of the digestive tract may also be
involved. Angioedema may be due to physical agents.
Often the cause remains unknown.

Diagnosis
Visual examination of the symptoms usually diagnoses the reaction. Further skin tests and review of the
patient’s photosensitivity may reveal a cause.

Treatment
Removing the offending agent is the first step to
treatment. If sun is involved, shade and sunscreens are
necessary. The reaction can usually be controlled with
epinephrine, antihistamines, or cortisone-like drugs.
Urticaria may be treated with antihistamines such
as diphenhydramine (Benadryl) or desloratadine
(Clarinex). Clarinex is non-sedating, meaning it will
not make patients drowsy. Itching can be controlled
with cold packs or commercial topical agents that
contain menthol, camphor, eucalyptus oil, aloe, antihistamines, or cortisone preparations.

Prognosis
If the causative agent has been diagnosed, avoidance
of or protection against the allergen cures the allergy.
Usually, allergies can be managed through treatment.
Resources
PERIODICALS

Kirn, F. Timothy. ‘‘Desloratadine Improves Urticaria in
Clinical Setting.’’ Skin & Allergy News September
2004: 41.

J. Ricker Polsdorfer, MD
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Physical examination
Definition
A physical examination is an evaluation of the
body and its functions using inspection, palpation
(feeling with the hands), percussion (tapping with the
fingers), and auscultation (listening). A complete
health assessment also includes gathering information
about a person’s medical history and lifestyle, doing
laboratory tests, and screening for disease.

Purpose
The annual physical examination has been
replaced by the periodic health examination. How
often this is done depends on the patient’s age, sex,
and risk factors for disease. The United States
Preventative Services Task Force (USPSTF) has
developed guidelines for preventative health examinations that health care professionals widely follow.
Organizations that promote detection and prevention
of specific diseases, like the American Cancer Society,
generally recommend more intensive or frequent
examinations.
A comprehensive physical examination provides
an opportunity for the healthcare professional to
obtain baseline information about the patient for
future use, and to establish a relationship before problems happen. It provides an opportunity to answer
questions and teach good health practices. Detecting a
problem in its early stages can have good long-term
results.

Precautions
The patient should be comfortable and treated
with respect throughout the examination. As the
examination procedes, the examiner should explain
what he or she is doing and share any relevant
findings.

Description
A complete physical examination usually starts at
the head and proceeds all the way to the toes.
However, the exact procedure will vary according to
the needs of the patient and the preferences of the
examiner. An average examination takes about 30
minutes. The cost of the examination will depend on
the charge for the professional’s time and any tests
that are done. Most health plans cover routine physical examinations including some tests.
2897

Physical examination

KEY TERMS

Physical examination

The patient should lie flat for:

The examination
First, the examiner will observe the patient’s
appearance, general health, and behavior, along with
measuring height and weight. The vital signs—including pulse, breathing rate, body temperature, and blood
pressure—are recorded.



Abdomen. Light and deep palpation is used on the
abdomen to feel the outlines of internal organs
including the liver, spleen, kidneys, and aorta, a
large blood vessel.



Rectum and anus. With the patient lying on the left
side, the outside areas are observed. An internal
digital examination (using a finger), is usually done
if the patient is over 40 years old. In men, the prostate
gland is also palpated.



Reproductive organs. The external sex organs are
inspected and the area is examined for hernias. In
men, the scrotum is palpated. In women, a pelvic
examination is done using a speculum and a
Papamnicolaou test (Pap test) may be taken.



Legs. With the patient lying flat, the legs are
inspected for swelling, and pulses in the knee, thigh,
and foot area are found. The groin area is palpated
for the presence of lymph nodes. The joints and
muscles are observed.



Musculoskeletel system. With the patient standing,
the straightness of the spine and the alignment of the
legs and feet is noted.



Blood vessels. The presence of any abnormally
enlarged veins (varicose), usually in the legs, is noted.

With the patient sitting up, the following systems
are reviewed:


Skin. The exposed areas of the skin are observed; the
size and shape of any lesions are noted.



Head. The hair, scalp, skull, and face are examined.



Eyes. The external structures are observed. The internal structures can be observed using an ophthalmoscope (a lighted instrument) in a darkened room.



Ears. The external structures are inspected. A lighted
instrument called an otoscope may be used to inspect
internal structures.



Nose and sinuses. The external nose is examined. The
nasal mucosa and internal structures can be observed
with the use of a penlight and a nasal speculum.



Mouth and pharynx. The lips, gums, teeth, roof of
the mouth, tongue, and pharynx are inspected.



Neck. The lymph nodes on both sides of the neck and
the thyroid gland are palpated (examined by feeling
with the fingers).





Back. The spine and muscles of the back are palpated
and checked for tenderness. The upper back, where
the lungs are located, is palpated on the right and left
sides and a stethoscope is used to listen for breath
sounds.
Breasts and armpits. A woman’s breasts are
inspected with the arms relaxed and then raised. In
both men and women, the lymph nodes in the armpits are felt with the examiner’s hands.While the
patient is still sitting, movement of the joints in the
hands, arms, shoulders, neck, and jaw can be
checked.

Then while the patient is lying down on the examining table, the examination includes:


Breasts. The breasts are palpated and inspected for
lumps.



Front of chest and lungs. The area is inspected with
the fingers, using palpation and percussion. A stethoscope is used to listen to the internal breath sounds.
The head should be slightly raised for:



Heart. A stethoscope is used to listen to the heart’s
rate and rhythm. The blood vessels in the neck are
observed and palpated.

2898

In addition to evaluating the patient’s alertness
and mental ability during the initial conversation,
additional inspection of the nervous system may be
indicated:


Neurologic screen. The patient’s ability to take a few
steps, hop, and do deep knee bends is observed. The
strength of the hand grip is felt. With the patient
sitting down, the reflexes in the knees and feet can
be tested with a small hammer. The sense of touch in
the hands and feet can be evaluated by testing reaction to pain and vibration.



Sometimes additional time is spent examining the 12
nerves in the head (cranial) that are connected
directly to the brain. They control the sense of
smell, strength of muscles in the head, reflexes in
the eye, facial movements, gag reflex, and muscles
in the jaw. General muscle tone and coordination,
and the reaction of the abdominal area to stimulants
like pain, temperature, and touch would also be
evaluated.

Preparation
Before visiting the health care professional, the
patient should write down important facts and dates
about his or her own medical history, as well as those
GALE ENCYCLOPEDIA OF MEDICINE

Auscultation—The process of listening to sounds
that are produced in the body. Direct auscultation
uses the ear alone, such as when listening to the
grating of a moving joint. Indirect auscultation
involves the use of a stethoscope to amplify the
sounds from within the body, like a heartbeat.
Hernia—The bulging of an organ, or part of an
organ, through the tissues normally containing it;
also called a rupture.
Inspection—The visual examination of the body
using the eyes and a lighted instrument if needed.
The sense of smell may also be used.
Ophthalmoscope—Lighted device for studying the
interior of the eyeball.
Otoscope—An instrument with a light for examining the internal ear.
Palpation—The examination of the body using the
sense of touch. There are two types: light and deep.
Percussion—An assessment method in which the
surface of the body is struck with the fingertips to
obtain sounds that can be heard or vibrations that
can be felt. It can determine the position, size, and
consistency of an internal organ. It is done over the
chest to determine the presence of normal air content in the lungs, and over the abdomen to evaluate
air in the loops of the intestine.
Reflex—An automatic response to a stimulus.
Speculum—An instrument for enlarging the opening of any canal or cavity in order to facilitate
inspection of its interior.
Stethoscope—A Y-shaped instrument that amplifies body sounds such as heartbeat, breathing, and
air in the intestine. Used in auscultation.
Varicose veins—The permanent enlargement and
twisting of veins, usually in the legs. They are most
often seen in people with occupations requiring
long periods of standing, and in pregnant women.

of family members. He or she should have a list of all
medications with their doses or bring the actual bottles
of medicine along. If there are specific concerns about
anything, writing them down is a good idea.
Before the physical examination begins, the bladder should be emptied and a urine specimen can be
collected in a small container. For some blood tests,
the patient may be told ahead of time not to eat or
drink after midnight.
GALE ENCYCLOPEDIA OF MEDICINE

The patient usually removes all clothing and puts
on a loose-fitting hospital gown. An additional sheet is
provided to keep the patient covered and comfortable
during the examination.

Aftercare
Once the physical examination has been completed, the patient and the examiner should review
what laboratory tests have been ordered and how the
results will be shared with the patient. The medical
professional should discuss any recommendations for
treatment and follow-up visits. Special instructions
should be put in writing. This is also an opportunity
for the patient to ask any remaining questions about
his or her own health concerns.

Normal results
Normal results of a physical examination correspond to the healthy appearance and normal functioning of the body. For example, appropriate reflexes will
be present, no suspicious lumps or lesions will be
found, and vital signs will be normal.

Abnormal results
Abnormal results of a physical examination
include any findings that indicated the presence of a
disorder, disease, or underlying condition. For example, the presence of lumps or lesions, fever, muscle
weakness or lack of tone, poor reflex response, heart
arhythmia, or swelling of lymph nodes will point to a
possible health problem.
Resources
BOOKS

Bates, Barbara. A Guide to Physical Examination and
History Taking. Philadelphia: Lippincott Co., 1995.

Karen Ericson, RN

Physical therapy see Rehabilitation

Pica
Definition
Pica is the persistent craving and compulsive eating
of nonfood substances. The Diagnostic and Statistical
Manual of Mental Disorders, fourth edition, classifies
it as a feeding and eating disorder of childhood.
2899

Pica

KEY TERMS

Pica

Description
The puzzling phenomenon of pica has been
recognized and described since ancient times. Pica
has been observed in ethnic groups worldwide, in
both primitive and modernized cultures, in both sexes,
and in all age groups. The word pica comes from the
Latin name for magpie, a bird known for its unusual
and indiscriminate eating habits. In addition to
humans, pica has been observed in other animals,
including the chimpanzee.
Pica in humans has many different subgroups,
defined by the substance that is ingested. Some of the
most commonly described types of pica are eating
earth, soil or clay (geophagia), ice (pagophagia) and
starch (amylophagia). However, pica involving dozens
of other substances, including cigarette butts and
ashes, hair, paint chips, and paper have also been
reported. In one unusual case, the patient ingested
transdermal patches of fentanyl, an opioid medication
given for severe pain. Eating the skin patch increased
the patient’s dose of the drug by a factor of 10.
Although pica can occur in individuals of any
background, a higher incidence of pica is associated
with:


pregnancy



developmental delay and mental retardation



psychiatric disease and autism



early childhood



poor nutrition or low blood levels of iron and other
minerals



certain cultural or religious traditions

Causes and symptoms
Evidence suggests that there may be several causes
of pica. One widely held theory points to iron deficiency as a major cause of pica. Several reports have
described pica in individuals with documented iron
deficiency, although there has been uncertainty as to
whether the iron deficiency was a cause of pica or a
result of it. Because some substances, such as clay, are
believed to block the absorption of iron into the
bloodstream, it was thought that low blood levels of
iron could be the direct result of pica. However, some
studies have shown that pica cravings in individuals
with iron deficiency stop once iron supplements are
given to correct the deficiency. Another study looked
specifically at the rate of iron absorption during pica
conditions and normal dietary behavior, and showed
that the iron absorption was not decreased by pica. In
addition, low blood levels of iron commonly occur in
2900

pregnant women and those with poor nutrition, two
populations at higher risk for pica. Such findings offer
strong support of iron deficiency as a cause, rather
than result, of pica.
Other reports suggest that pica may have a psychological basis and may even fall into the spectrum
of obsessive-compulsive disorder. Pica has a higher
incidence in populations with an underlying diagnosis
involving mental functioning. These diagnoses include
psychiatric conditions like schizophrenia, developmental disorders including autism, and conditions
with mental retardation. These conditions are not
characterized by iron deficiency, which supports a
psychological component in the cause of pica.
Cultural and religious traditions may also play a
role in pica behavior. In some cultures, nonfood substances are believed to have positive health or spiritual
effects. Among some African Americans in the south,
ingesting a particular kind of white clay is believed to
promote health and reduce morning sickness during
pregnancy. Other cultures practice pica out of belief
that eating a particular substance may promote fertility or bring good luck.
The hallmark feature of pica, consistently consuming nonfood substances, often does not present publicly. People may be embarrassed to admit to these
unusual eating habits, and may hide it from their family
and physician. In other cases, an individual may not
report the pica to a physician simply because of a lack
of knowledge of pica’s potential medical significance.
Because the eating behaviors of pica are not usually
detected or reported, it is the complications of the
behavior that bring it to attention. Complications
vary, depending on the type of pica. Geophagia has
potential side effects that most commonly affect the
intestine and bowel. Complications can include constipation, cramping, pain, obstruction caused by formation of an indigestible mass, perforation from sharp
objects like rocks or gravel, and contamination and
infection from soil-dwelling parasites.
Amylophagia usually involves the consumption
of cornstarch and, less frequently, laundry starch.
The high caloric content of starch can cause excessive
weight gain, while at the same time leading to malnutrition, as starch contributes ‘‘empty’’ calories lacking
vitamins and minerals. Amylophagia during pregnancy can mimic gestational diabetes in its presentation and even in its potential harmful effects on
the fetus.
Pica involving the ingestion of substances such
as lead-based paint or paper containing mercury
can cause symptoms of toxic poisoning. Compulsive
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
In order for the diagnosis of pica to be made, there
must be a history of persistent consumption of a
nonfood substance continuing for a minimum period
of one month. Infants and toddlers are typically
excluded from this diagnosis since mouthing objects
is a normal developmental behavior at that age.
Individuals with mental retardation who function at
or below an approximate cognitive level of 18 months
may also be exempt form this diagnosis.
Pica is most often diagnosed when a report of such
behaviors can be provided by the patient or documented by another individual. In other cases, pica is diagnosed after studies have been performed to assess the
presenting symptoms. For example, imaging studies
ordered to assess severe gastrointestinal complaints
may reveal intestinal blockage with an opaque substance; such a finding is suggestive of pica. Biopsy of
intestinal contents can also reveal findings, such as
parasitic infection, consistent with pica. Pica may
also be suspected if abnormal levels of certain minerals
or chemicals are detected in the blood.
Pica in pregnant women is sometimes diagnosed
after childbirth because of a health problem in the
newborn caused by the substance(s) ingested by the
mother. In one instance reported in Chicago, a newborn girl was treated for lead poisoning caused by
her mother’s eating fragments of lead-glazed pottery
during pregnancy.

Treatment
Treatment of pica will often depend on the cause
and type of pica. Conventional medical treatment may
be appropriate in certain situations. For example,
supplementation with iron-containing vitamins has
been shown to cause the unusual cravings to subside
in some iron-deficient patients.
Medical complications and health threats, including high lead levels, bowel perforation or intestinal
obstruction, will require additional medical management, beyond addressing the underlying issue of pica.

Alternative treatment
Because most cases of pica do not have an obvious
medical cause, treatment with counseling, education,
and nutritional management is often more successful
GALE ENCYCLOPEDIA OF MEDICINE

Pica

consumption of even a seemingly harmless substance
like ice (pagophagia) can have negative side effects,
including decreased absorption of nutrients by the gut.

KEY TERMS
Amylophagia—The compulsive eating of purified
starch, typically cornstarch or laundry starch.
Geophagia—The compulsive eating of earthy substances, including sand, soil, and clay.
Pagophagia—The compulsive eating of ice.

and more appropriate than treatment with medication. Some therapists specializing in eating disorders
may have expertise in treating pica.

Prognosis
The prognosis for individuals with pica varies
greatly, according to the type and amount of substance ingested, the extent of presenting side effects,
and the success of treatment. Many of the side effects
and complications of pica can be reversed once the
behavior is stopped, while other complications,
including infection and bowel perforation, pose significant health threats and if not successfully treated may
result in death.
When seen in children, pica behavior tends to
lessen with age. However, individuals with a history
of pica are more likely to experience it again.
Counseling and nutritional education can reduce the
risk of recurrence.

Prevention
There are no known methods of preventing pica.
However, once pica is known or suspected, measures
can be taken to reduce further ingestion of nonfood
substances. Removing the particular substance from
readily accessible areas can be helpful. Close observation of the individual with pica may limit inappropriate eating behaviors.
Resources
BOOKS

American Psychiatric Association.Diagnostic and Statistical
Manual of Mental Disorders. 4th ed, revised.
Washington, DC: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Anemias.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Malnutrition.’’ Section 1, Chapter 2 In The Merck
2901

Pickwickian syndrome

Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2002.
PERIODICALS

Jackson, W. Clay. ‘‘Amylophagia Presenting as Gestational
Diabetes.’’ Archives of Family Medicine 9 (July 2000):
649–652.
Kirschner, Jeffrey. ‘‘Management of Pica: A Medical
Enigma.’’ American Family Physician 63, no. 6 (March
15, 2001): 1169. <http://www.aafp.org/afp/20010315/
tips/9.html>.
Liappas, I. A., N. P. Dimopoulos, E. Mellos, et al. ‘‘Oral
Transmucosal Abuse of Transdermal Fentanyl.’’
Journal of Psychopharmacology 18 (June 2004):
277–280.
Moya, J., C. F. Bearer, and R. A. Etzel. ‘‘Children’s
Behavior and Physiology and How It Affects Exposure
to Environmental Contaminants.’’ Pediatrics 113 (April
2004): 996–1006.
Mycyk, M. B., and J. B. Leikin. ‘‘Combined Exchange
Transfusion and Chelation Therapy for Neonatal Lead
Poisoning.’’ Annals of Pharmacotherapy 38 (May 2004):
821–824.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry.
3615 Wisconsin Avenue, NW, Washington, DC
20016-3007. (202) 966-7300. Fax: (202) 966-2891.
<http://www.aacap.org>.
OTHER

‘‘Pica: Dirt Eating or ‘Geophagy’.’’ Support, Concern and
Resources For Eating Disorders, 2000. <http://
www.eating-disorder.org/pica.html>.
‘‘Pica.’’ KidsHealth. The Nemours Foundation, 2001.
<http://kidshealth.org/parent/emotions/
behavior/pica.html>.

Stefanie B. N. Dugan, M.S.
Rebecca J. Frey, PhD

KEY TERMS
Latency—The period of inactivity between the
time a stimulus is provided and the time a response
occurs.
Obesity—Exceeding one’s normal weight by 20%.
A person suffering from extreme obesity would
exceed their normal weight by a much higher
percentage.
Pulmonary system—Lungs and respiratory system
of the body.

The major health problem that occurs in patients
with this disease is sleep apnea. This is caused in part
by the excess amounts of fatty tissue surrounding the
chest muscles. This excess fat places a strain on the
heart, lungs, and diaphragm of the patient, making it
difficult to breathe.

Causes and symptoms
The major cause of Pickwickian syndrome is
extreme obesity. This obesity places an excessive
load on the pulmonary system. The role of genetics
is also being studied. Symptoms of Pickwickian
syndrome include excessive daytime sleepiness,
shortness of breath due to elevated blood carbon
dioxide pressure, disturbed sleep at night, and
flushed face. The skin can also have a bluish tint,
and the patient may have high blood pressure, an
enlarged liver, and an abnormally high red blood
cell count.

Diagnosis

Pickwickian syndrome
Definition
A group of symptoms that generally accompany
massive obesity.

Some tests that can be used to diagnose this condition include echocardiography to determine heart
enlargement or pulmonary hypertension. Giving the
patient multiple sleep latency tests can help give an
objective measurement of daytime sleepiness.
Magnetic resonance imaging (MRI), computed tomography (CT) scans, or fiberoptic evaluation of the
upper airway may also be used.

Description
Pickwickian syndrome is a complex of symptoms
that primarily affect patients with extreme obesity.
The syndrome is named after a character in a Charles
Dickens novel, The Pickwick Papers, who seemed to
show some of the traits of this disease.
2902

Treatment
The primary treatment for Pickwickian syndrome
is focused on weight loss and increased physical activity. Also, medroxyprogesterone may help improve the
condition.
GALE ENCYCLOPEDIA OF MEDICINE

Pickwickian sydnrome is entirely reversible if it is
diagnosed and treated properly. If the problem goes
undiagnosed, the outcome can be fatal.

Prevention
Prevention of Pickwickian syndrome can be
achieved by maintaining a healthy body weight and
getting the proper amount of exercise. For prevention
of the sleep apnea that generally accompanies
Pickwickian syndrome, there are several possible
treatments. If the sleep apnea is only present when
the patient is flat on their back, a tennis ball can be
sewn into the sleep clothes to remind the patient not to
sleep on their back. For more severe cases of sleep
apnea, a tonsillectomy or the use of dental appliances
may be recommended.
Resources
BOOKS

Dambro, Mark R. The 5-Minute Clinical Consult.
Baltimore: Williams & Wilkins, 2001.
Tierney, Lawrence, et. al. Current Medical Diagnosis and
Treatment. Los Altos: Lange Medical Publications,
2001.
PERIODICALS

‘‘‘Apples’ and ‘Pears’: Defining the Shape of the Problem.’’
FP Report 6 (November2000).
Kushner, Robert F., and Roland L. Weinsier. ‘‘Evlauation
of theObese Patient.’’ Medical Clinics of North America
84 (March2000).

Kim A. Sharp, M.Ln.

PID see Pelvic inflammatory disease

Piercing and tattoos
Definition
Body piercing and tattoos are a popular form of
body art that have been practiced throughout history
by various cultures.

Description
Various cultures have embraced adorning their
bodies with piercings and tattoos throughout history.
In 1992, the 4,000-year-old body of a tattooed man
was discovered in a glacier on the Austrian border,
GALE ENCYCLOPEDIA OF MEDICINE

and historical research has shown that Egyptians identified tattooing with fertility and nobility in the period
from 4000–2000 BC Similar to tattooing, body piercing also has a rich history, which includes being used
as a symbol of royalty and courage. In some hunting
and gathering societies, body piercing and tattoos
have long been used in initiation rites and as socialization/enculturation symbols.
In today’s industrialized cultures, tattoos and
piercing are a popular art form shared by people of
all ages. They also are indicative of a psychology of
self-mutilation, defiance, independence, and belonging, as for example in prison or gang cultures.
Popular piercing sites include the ear, nasal septum, eyebrow, tongue, cheek, navel, labia, and penis.
Tattoos permanently mark various areas on the body.
Piercing is performed quickly and without
anesthesia by either a spring-loaded ear-piercing gun
or piercing needles, with the needle diameter varying
from six to 18 gauge. The skin is cleaned, then the
needle and jewelry are inserted through the tissue in
one swift motion. Piercing is typically completed in
tattoo or beauty parlors.
Originating from the Tahitian word tattau, meaning ‘‘to mark,’’ tattoos are relatively permanent marks
or designs on the skin. An electric needle injects
colored pigment into small deep holes made in the
skin to form the tattoo. Prison tattoo techniques are
usually very crude, in marked contrast to the highly
skilled art practiced in Japan and also performed in
America and Europe. In recent years, the ancient art
of Mehndi, or temporary tattooing of the skin with a
paste made of henna has become popular America and
around the world. Henna is a stain normally made for
hair, and therefore exempt from U.S. Food and Drug
Administration (FDA) regulation. Although seemingly safe because it does not pierce the skin, henna
tattoos using black henna, a paste that contains parahenylenediamine, can actually be dangerous when
absorbed into the skin of some people.

Causes and symptoms
While piercing and tattooing are popular, both
present definite health risks. Tattoos can lead to the
transmission of infectious diseases, such as hepatitis B
and C, and theoretically HIV, when proper sterilization and safety procedures are not followed. Black
henna tattoos can cause significant allergies and
rashes, leading to renal (kidney) failure and even
death in those who are sensitive to their ingredients.
These types of tattoos have appeared particularly
2903

Piercing and tattoos

Prognosis

Piercing and tattoos

dangerous to young children. Body piercing also presents the risk of chronic infection, scarring, hepatitis B
and C, tetanus, and skin allergies to the jewelry that is
used. A recent Mayo Clinic study reported that 17%
of college students with piercings suffered a medical
complication such as infection or tearing. Use of piercing guns and preferences for upper ear piercing have
led to increased infections in recent years. The force of
the gun’s delivery further complicates matters around
the delicate cartilage of the upper ear and some people
require surgical intervention.
Body piercing and tattooing are unregulated in
most United States, but illegal in some. The
American Dental Association (ADA) opposes oral
(tongue, lip or cheek) piercing, and the American
Academy of Dermatology is against all forms of
body piercing except ear lobe piercing.

Diagnosis
Some of the signs of an infection from either piercing or tattoos are obvious, such as inflammation of
the pierced or tattooed area, while the symptoms of
hepatitis C, the most common blood-borne infection
in the United States, may not be so obvious. Allergic
responses to tattoos may occur due to the pigment
compounds used, such as oxides of iron, mercury,
chromium, cadmium, and cobalt and synthetic
organic dyes. Symptoms of an allergic reaction include
swelling, redness and severe itching. Symptoms of
henna tattoo reactions are an eczema-like rash around
the tattoo site. The patch should be tested for reaction
severity before it proceeds to anaphylactic shock, or
severe allergic reaction.
Most infections from piercing are due to the use of
non-sterile techniques. The skin pathogens streptococcus and staphylococcus are most frequently involved
in skin infections from piercing. The fleshy tissue
around the pierced area may weaken and tear, leading
for example, to a badly disfigured earlobe. Other common complications include contact dermatitis and
scars. Piercing can result in endocarditis, urethral rupture, and a serious infection of the penis foreskin
leading to severe disability or even death.

Treatment
Treatment of a local infection from piercing
includes warm compresses and antibacterial ointment
for local infections, to a five-day course of oral antibiotic therapy. If hepatitis B or C is confirmed, a series
of diet and lifestyle changes, such as the elimination of
alcohol, is recommended to control the disease.
2904

Tattoo artist Michael Wilson displaying his own tattoos and
piercings. (Photograph by Susan Mc Cartney, Photo Researchers.
Reproduced by permission.

There are four methods to remove tattoos, including: surgical removal that involves cutting the tattoo
away; sanding the skin with a wire brush to remove the
epidermis and dermis layers in a process called dermabrasion; using a salt solution to soak the tattooed
skin (salabrasion); and scarification, removing the
tattoo with an acid solution to form a scar in its
place. Topical steroids can often treat reactions to
henna tattoos, but improvement may take several
weeks.

Prognosis
Depending on the type of infection resulting from
either piercing or tattoos, the treatment and prognosis
vary. Minor infections respond well to antibiotic therapy, while blood borne diseases such as hepatitis B and
C cause life-altering results. Disfigurement may or
may not be fully correctable by later plastic surgery.
GALE ENCYCLOPEDIA OF MEDICINE

Endocarditis—Infection of a valve inside the heart.
Hepatitis—Inflammation of the liver.
Socialization—Process by which new members of
a social group are integrated in the group.

‘‘Perichondritis: A Complication of Piercing Auricular
Cartridge.’’ Postgraduate Medical Journal January
2003: 29–31.
Sullivan, Michele G. ‘‘Henna Tattoos Tied to Bad Allergic
Reactions.’’ Family Practice News May 15, 2003: 16.
Weir, Erica. ‘‘Navel Gazing: A Clinical Glimpse at Body
Piercing.’’ Canadian Medical Association Journal
(March 2001): 864.

Beth A. Kapes
Teresa G. Odle

Patients particularly sensitive or allergic to the ingredients in black henna may suffer serious consequences,
even death, if their reaction progresses. Others may be
left with scarring or altered pigmentation along the
tattoo design.

Prevention
The best way to prevent infection from piercing or
tattoos is not to get one in the first place. Procedures
should be performed in a sterile environment by an
experienced professional. The person performing the
procedure should remove a new needle from the plastic in front of you and should put on a new pair of
sterile gloves. Anyone considering a henna tattoo
should require proof from the artists that he or she is
using pure, safe brown henna, not the unsafe black
henna.

Pilates
Definition
Pilates or Physical Mind method, is a series of nonimpact exercises designed by Joseph Pilates to develop
strength, flexibility, balance, and inner awareness.

Purpose

PERIODICALS

Pilates is a form of strength and flexibility training
that can be done by someone at any level of fitness.
The exercises can also be adapted for people who have
limited movement or who use wheel chairs. It is an
engaging exercise program that people want to do.
Pilates promotes a feeling of physical and mental
well-being and also develops inner physical awareness.
Since this method strengthens and lengthens the muscles without creating bulk, it is particularly beneficial
for dancers and actors. Pilates is also helpful in preventing and rehabilitating from injuries, improving
posture, and increasing flexibility, circulation, and
balance. Pregnant women who do these exercises can
develop body alignment, improve concentration, and
develop body shape and tone after pregnancy.
According to Joseph Pilates, ‘‘You will feel better in
10 sessions, look better in 20 sessions and have a
completely new body in 30 sessions.’’

Abbasi, Kamran. ‘‘Body Piercing.’’ BritishMedical Journal
April 14, 2001: 936.
Brown, Kelli McCormack, Paula Perlmutter, and Robert
J.McDermott. ‘‘Youth and Tattoos: What School
Health Personnel Should Know.’’ Journal of School
Health November 2000: 355.
Califano, Julie. ‘‘Piercing Peril: Adorning Your Body can
Backfire Big Time.’’ Cosmopolitan (April 2003: 112.
Edy, Carolyn. ‘‘Body Piercing Woes: One More Reason to
Think Twice Before Getting Your Navel Pierced.’’
Yoga Journal June 30, 2000: 36.
‘‘Hazards with Henna Tattoos.’’ Pulse June 23, 2003: 60.

Although Pilates is often associated with dancers,
athletes, and younger people in general who are interested in improving their physical strength and flexibility, a simplified version of some Pilates exercises is also
being used as of 2003 to lower the risk of hospitalrelated deconditioning in older adults. A Canadian
study of hospitalized patients over the age of 70
found that those who were given a set of Pilates exercises that could be performed in bed recovered more
rapidly than a control group given a set of passive
range-of-motion exercises.

Piercing should be completed with smoothly
polished jewelry made of 14 or 18 carat gold, titanium,
surgical steel or niobium. An allergic reaction can
result with the use of jewelry made of brass plate or
containing a nickel alloy. Healing time from a piercing
range from six months to two years. A piercing should
be completed in a sterile environment that uses every
precaution to reduce the risk of infection. Excessive
force, such as exerting a strong pull, should never be
applied to jewelry inserted into pierced body parts to
avoid tearing and injuring the tissues.
Resources

GALE ENCYCLOPEDIA OF MEDICINE

2905

Pilates

KEY TERMS

Pilates

Description

KEY TERMS

Origins
Joseph Pilates (pronounced pie-LAH-tes), the
founder of the Pilates method (also simply referred
to as ‘‘the method’’) was born in Germany in 1880.
As a frail child with rickets, asthma, and rheumatic
fever, he was determined to become stronger. He dedicated himself to building both his body and his mind
through practices which included yoga, zen, and
ancient Roman and Greek exercises. His conditioning
regime worked and he became an accomplished gymnast, skier, boxer, and diver.
While interned in England during World War I
for being a German citizen, Pilates became a nurse.
During this time, he designed a unique system of
hooking springs and straps to a hospital bed in order
to help his disabled and immobilized patients regain
strength and movement. It was through these experiments that he recognized the importance of training
the core abdominal and back muscles to stabilize the
torso and allow the entire body to move freely. This
experimentation provided the foundation for his style
of conditioning and the specialized exercise equipment
associated with the Pilates method.
Pilates emigrated to the United States in 1926 after
the German government invited him to use his conditioning methods to train the army. That same year he
opened the first Pilates studio in New York City. Over
the years, dancers, actors, and athletes flocked to his
studio to heal, condition, and align their bodies.
Joseph Pilates died at age 87 in a fire at his studio.
Although his strength enabled him to escape the flames
by hanging from the rafters for over an hour, he died
from smoke inhalation. He believed that ideal fitness is
‘‘the attainment and maintenance of a uniformly developed body with a sound mind fully capable of naturally,
easily, and satisfactorily preforming our many and varied daily tasks with spontaneous zest and pleasure.’’
During the initial meeting, an instructor will analyze the client’s posture and movement and design a
specific training program. Once the program has been
created, the sessions usually follow a basic pattern. A
session generally begins with mat work and passive and
active stretching. In passive stretching, the instructor
moves and presses the client’s body to stretch and
elongate the muscles. During the active stretching period, the client preforms the stretches while the instructor watches their form and breathing. These exercises
warm up the muscles in preparation for the machine
work. The machines help the client to maintain the
correct positioning required for each exercise.
2906

Yoga—A system of physical, mental, and breathing
exercises developed in India.
Zen—A form of meditation that emphasizes direct
experience.

There are over 500 exercises that were developed
by Joseph Pilates. ‘‘Classical’’ exercises, according to
the Pilates Studio in New York involve several principles. These include concentration, centering, flowing
movement, and breath. Some instructors teach only
the classical exercises originally taught by Joseph
Pilates. Others design new exercises that are variations
upon these classical forms in order to make the exercises more accessible for a specific person.
There are two primary exercise machines used for
Pilates, the Universal Reformer and the Cadillac, and
several smaller pieces of equipment. The Reformer
resembles a single bed frame and is equipped with a
carriage that slides back and forth and adjustable
springs that are used to regulate tension and resistance. Cables, bars, straps, and pulleys allow the exercises to be done from a variety of positions. Instructors
usually work with their clients on the machines for
20–45 minutes. During this time, they are observing
and giving feedback about alignment, breathing, and
precision of movement. The exercises are done slowly
and carefully so that the movements are smooth and
flowing. This requires focused concentration and
muscle control. The session ends with light stretching
and a cool-down period.
Once the basics are learned from an instructor,
from either one-on-one lessons or in a class, it is possible to train at home using videos. Exercise equipment
for use at home is also available and many exercises
can be preformed on a mat.
A private session costs between $45–75 dollars,
depending on the part of the country one is in. This
method is not specifically covered by insurance
although it may be covered when the instructor is a
licensed physical therapist.

Precautions
The Pilates method is not a substitute for good
physical therapy, although it has been increasingly
used and recommended by physical therapists since
the mid-1980s. People with chronic injuries are
advised to see a physician.
GALE ENCYCLOPEDIA OF MEDICINE

As of early 2004, several physical therapists and
gerontologists have done research studies on the
Pilates method, although much more work needs to
be done in this area. One recent finding is that the
method should not be used by patients with lower
back pain, as it appears to be ineffective in treating
this condition.
The appeal of the Pilates method to a wide population, coupled with a new interest in it on the part of
rehabilitation therapists, suggests that further studies
may soon be underway. Dancers and actors originally
embraced the Pilates method as a form of strength
training that did not create muscle bulk. Professional
and amateur athletes also use these exercises to prevent reinjury. Sedentary people find Pilates to be a
gentle, non-impact approach to conditioning. Pilates
equipment and classes can be found in hospitals,
health clubs, spas, and gyms.
Resources
BOOKS

Pilates, Joseph H., et al. The Complete Writings of Joseph
Pilates: Return to Life Through Controlology and Your
Health. New York: Bantam Doubleday, 2000.
Siler, Brooke. The Pilates Body: The Ultimate At-Home
Guide to Strengthening, Lengthening and Toning Your
Body-Without Machines. New York: Bantam
Doubleday, 2000.
PERIODICALS

(212) 875-0189. Fax: (212) 769-2368. <http:\\www.
pilates-studio.com>.

Linda Chrisman
Rebecca J. Frey, PhD

Piles see Hemorrhoids

Pinguecula and pterygium
Definition
Pinguecula and pterygium are both non-malignant, slow-growing proliferations of conjunctival connective tissue in the eye. Pterygia, but not pingueculae,
extend over the cornea.

Description
The outer layer of the eyeball consists of the tough
white sclera and the transparent cornea. The cornea
lies in front of the colored part of the eye (iris).
Overlying the sclera is a transparent mucous membrane called the conjunctiva. The conjunctiva lines
the inside of the lids (palpebral conjunctiva) and covers the sclera (bulbar conjunctiva).
Pingueculae and pterygia are common in adults,
and their incidence increases with age. Pterygia are less
common than pingueculae.

Anderson, Brent D. ‘‘Pushing for Pilates.’’ Rehab
Management 14 (June-July 2001): 23–25.
Blum, C. L. ‘‘Chiropractic and Pilates Therapy for the
Treatment of Adult Scoliosis.’’ Journal of
Manipulative and Physiological Therapeutics 25 (May
2002): E3.
Coleman-Brown, L., and V. Haley-Kanigel. ‘‘Movement
with Meaning.’’ Rehab Management 16 (July 2003):
28–32.
Maher, C. G. ‘‘Effective Physical Treatment for Chronic
Low Back Pain.’’ Orthopedic Clinics of North America
35 (January 2004): 57–64.
Mallery, L. H., E. A. MacDonald, C. L. Hubley-Kozey,
et al. ‘‘The Feasibility of Performing Resistance
Exercise with Acutely Ill Hospitalized Older Adults.’’
BMC Geriatrics 3 (October 7, 2003): 3.

Pingueculae are seen as small, raised, thickenings
of the conjunctiva. They may be yellow, gray, white, or
colorless. They are almost always to one side of the
iris–not above or below–and usually on the side closest
to the nose. A pinguecula may develop into a
pterygium.

ORGANIZATIONS

The cause or causes of these disorders are
unknown, but they are more frequent in people who
live in sunny and windy climates and people whose
jobs expose them to ultraviolet (UV) light (for example, farmers and arc welders). Pingueculae and pterygia also occur in older people. It is thought these
growths are the result of UV or infrared light and

Physical Mind Institute. 1807 Second Street, Suite 15/16,
Santa Fe, New Mexico 87505. (505) 988-1990 or
(800) 505-1990. Fax: (505) 988-2837.
themethod@trail.com.
Pilates Studio. 2121 Broadway, Suite 201, New York, New
York, 10023-1786. (800)474-5283 or (888) 474-5283 or
GALE ENCYCLOPEDIA OF MEDICINE

Pterygia are conjunctival thickenings that may
have blood vessels associated with them. They often
have a triangular-shaped appearance. The pterygia
may also grow over the cornea and may therefore
affect vision.

Causes and symptoms
Causes

2907

Pinguecula and pterygium

Research and general acceptance

Pinguecula and pterygium

KEY TERMS
Astigmatism—Asymetric vision problems due to
irregularities in the cornea.
Beta radiation—Streams of electrons emitted by
beta emitters like carbon-14 and radium.
Conjuctiva—The mucous membrane that covers
the white part of the eyes and lines the eyelids.
Cornea—The clear outer covering of the front of the
eye. It is in front of the colored part of the eye (iris)
and the iris’s central black hole (pupil).
Pterygium, an overgrowth of the cornea, is usually on the
inner side of the eye by thickened and degenerative conjunctiva. (Photo Researchers, Inc. Reproduced by permission.)

irritation. It is also believed that prolonged exposure
to these risk factors (that is, UV light) increases the
chances of occurrence.
Symptoms
Although some people with pinguecula constantly
feel like they have a foreign body in their eye, most are
asymptomatic. Because the lids can no longer spread
the tears over a smooth area, dry areas may result.
Some people with a pterygium are also asymptomatic;
some feel like they have a foreign body in their eye.
Because a pterygium can stretch and distort the cornea, some people acquire astigmatism from a
pterygium.

Diagnosis
An eye doctor (ophthalmologist or optometrist)
can usually diagnose pingueculae and pterygia by
external observation, generally using an instrument
called a slit lamp. A slit lamp is a microscope with a
light source and magnifies the structures of the eye for
the examiner. However, because pingueculae and pterygia can sometimes look similar to more serious eye
growths, it is important for people to have them
checked by an eye care professional.

Treatment
Usually, no treatment is needed. Artificial tears
can be used to relieve the sensation of a foreign body in
the eye and to protect against dryness. Surgery to
remove the pinguecula or pterygium is advisable
when the effect on the cornea causes visual defects or
when the thickening is causing excessive and recurrent
discomfort or inflammation. Sometimes surgical
2908

removal is also performed for cosmetic reasons.
However, healing from this type of surgery, although
usually painless, takes many weeks, and there is a high
rate of recurrence (as high as 50–60% in some
regions). Accordingly, surgery is avoided unless problems due to the pinguecula or pterygium are
significant.
Several methods have been used to attempt to
reduce the recurrence of the pinguecula or pterygium after surgery. One method that should be
abandoned is beta radiation. Although it is effective at slowing the regrowth of pingueculae and
pterygia, it can cause cataracts. A preferable
method is the topical application of the anticancer
drug, mitomycin-C.

Prognosis
Most pingueculae and pterygia grow slowly and
almost never cause significant damage, so the prognosis is excellent. Again, a diagnosis must be made to
rule out other more serious disorders.

Prevention
There is nothing that has been clearly shown to
prevent these disorders, or to prevent a pinguecula
from progressing to a pterygium. However, the presence of pingueculae and pterygia have been linked to
exposure to UV radiation. For that reason, UV exposure should be reduced. The American Optometric
Association (AOA) suggests that sunglasses should
block 99–100% of UV-A and UV-B rays. Patients
should speak to their eye care professionals about
protective coatings on sunglasses or regular spectacles.
Protecting the eyes from sunlight, dust, and other
environmental irritants is a good idea.
GALE ENCYCLOPEDIA OF MEDICINE

Pinta

Resources

KEY TERMS

ORGANIZATIONS

New York University (NYU), Department of Ophthalmology.
550 First Ave., New York, NY 10016. (212) 263-6433.
<http://ophth-www.med.nyu.edu/Ophth>.

Lesion—An abnormal change in skin due to
disease.

Lorraine Lica, PhD

Pinkeye see Conjunctivitis

Pinta
Definition
A bacterial infection of the skin which causes red
to bluish-black colored spots.

Description
Pinta is a skin infection caused by the bacterium
Treponema carateum, a relative of the bacterium
which causes syphilis. The word ‘‘pinta’’ comes from
the Spanish and means ‘‘painted.’’ Pinta is also known
as ‘‘azula’’ (blue), and ‘‘mal de pinto’’ (pinto sickness).
It is one of several infections caused by different
Treponema bacteria, which are called ‘‘endemic’’ or
‘‘non-venereal’’ treponematoses.
Pinta is primarily found in rural, poverty-stricken
areas of northern South America, Mexico, and the
Caribbean. The disease is usually acquired during
childhood and is spread from one person to another
by direct skin-to-skin contact. The bacteria enter the
skin through a small cut, scratch, or other skin
damage. Once inside the skin, the warmth and moisture allow the bacteria to multiply. The bacterial infection causes red, scaly lesions on the skin.

Causes and symptoms
Pinta is caused by an infection with the bacterium
Treponema carateum. Persons at risk for pinta are
those who live in rural, poverty-stricken, overcrowded
regions of South America, Mexico, and the
Caribbean. Symptoms of pinta occur within two to
four weeks after exposure to the bacteria. The first sign
of infection is a red, scaly, slowly enlarging bump on
the skin. This is called the ‘‘primary lesion.’’ The primary lesion usually appears at the site where the bacteria entered the skin. This is often on the arms, legs, or
face. The smaller lesions which form around the primary lesion are called ‘‘satellite lesions.’’ Lymph nodes
GALE ENCYCLOPEDIA OF MEDICINE

located near the infected area will become enlarged,
but are painless.
The second stage of pinta occurs between one and
12 months after the primary lesion stage. Many flat,
red, scaly, itchy lesions called ‘‘pintids’’ occur either
near the primary lesion, or scattered around the body.
Pintid lesions progress through a range of color
changes, from red to bluish-black. The skin of older
lesions will become depigmented (loss of normal color).

Diagnosis
Pinta can be diagnosed by dermatologists (doctors who specialize in skin diseases) and infectious
disease specialists. The appearance of the lesions
helps in the diagnosis. A blood sample will be taken
from the patient’s arm to test for antibodies to
Treponema carateum. A scraping of a lesion will be
examined under the microscope to look for Treponema
bacteria. The results of these tests should be available
within one to two days.

Treatment
Pinta is treated with benzathine penicillin G
(Bicillin), given as a single injection.

Prognosis
Treatment will result in a complete cure but will
not undo any skin damage caused by the late stages of
disease. Spread of pinta to the eyes can cause eyelid
deformities.

Prevention
Good personal hygiene and general health may
help prevent infections. In general, avoid physical contact with persons who have skin lesions.
Resources
OTHER

Mayo Clinic Online. March 5, 1998. <http://
www.mayohealth.org>.

Belinda Rowland, PhD
2909

Pituitary dwarfism

Pinworm infection see Enterobiasis
Pituitary adenoma see Pituitary tumors

Pituitary dwarfism
Definition
Dwarfism is a condition in which the growth of
the individual is very slow or delayed. There are many
forms of dwarfism. The word pituitary is in reference
to the pituitary gland in the body. This gland regulates
certain chemicals (hormones) in the body. Therefore,
pituitary dwarfism is decreased bodily growth due to
hormonal problems. The end result is a proportionate
little person, because the height as well as the growth
of all other structures of the individual are decreased.

Description
Pituitary dwarfism is caused by problems arising
in the pituitary gland. The pituitary gland is also called
the hypophysis. The pituitary gland is divided into two
halves: the anterior (front) and posterior (back)
halves. The anterior half produces six hormones:
growth hormone, adrenocorticotropin (corticotropin), thyroid stimulating homone (thyrotropin), prolactin, follicle stimulating hormone, and lutenizing
hormone. The posterior pituitary gland only produces
two hormones. It produces antidiuretic hormone
(vasopressin) and oxytocin.
Most forms of dwarfism are a result of decreased
production of hormones from the anterior half of the
pituitary gland. The most common form is due to
decreases of growth hormone which will be discussed
here. These decreases during childhood cause the individual’s arms, legs, and other structures to develop
normal proportions for their bodies, but at a
decreased rate.
When all of the hormones of the anterior pituitary
gland are not produced, this is called panhypopituitarism. Another type of dwarfism occurs when only the
growth hormone is decreased. Dwarfism can also
result from a lack of somatomedin C (also called insulin like growth factor, IGF-1) production.
Somatomedin C is a hormone produced in the liver
that increases bone growth when growth hormone is
present. The African pygmy and the Levi-Lorain
dwarfs lack the ability to produce somatomedin C in
response to growth hormone. All causes of dwarfism
lead to a proportionate little person.
2910

Growth is the body’s response to different hormones. The forebrain contains a small organ called the
hypothalamus, which is responsible for releasing hormones in response to the body’s needs for purposes of
regulation. Growth hormone is produced in the anterior pituitary gland when growth hormone-releasing
hormone (GHRH), is released by the hypothalamus.
Growth hormone is then released and stimulates the
liver to produce IGF-1. In return, IGF-1 stimulates
the long bones to grow in length. Thus, growth can be
slowed down or stopped if there is a problem making
any of these hormones or if there is a problem with the
cells receiving these hormones.
Some estimates show that there are between
10,000 and 15,000 children in the United States who
have growth problems due to a deficiency of growth
hormone.

Causes and symptoms
Pituitary dwarfism has been shown to run in
families. New investigations are underway to determine the specific cause and location of the gene
responsible for dwarfism. The human cell contains 46
chromosomes arranged in 23 pairs. Most of the genes
in the two chromosomes of each pair are identical or
almost identical with each other. However, with
dwarfism, there appears to be disruption on different
areas of chromosome 3 and 7. Some studies have
isolated defects for the production of pituitary hormones to the short arm (the ‘‘p’’ end) of chromosome
3 at a specific location of 3p11. Other studies have
found changes on the short arm of chromosome 7.
A child with a growth hormone deficiency is often
small with an immature face and chubby body build.
The child’s growth will slow down and not follow the
normal growth curve patterns. In cases of tumor, most
commonly craniopharyngioma (a tumor near the
pituitary gland), children and adolescents may present
with neurological symptoms such as headaches, vomiting, and problems with vision. The patient may also
have symptoms of double vision. Symptoms such as
truly bizarre and excessive drinking behaviors (polydipsia) and sleep disturbances may be common.

Diagnosis
The primary symptom of pituitary dwarfism is
lack of height. Therefore, a change in the individual’s
growth habits will help lead to a diagnosis. Another
diagnostic technique uses an x ray of the child’s hand
to determine the child’s bone age by comparing this to
the child’s actual chronological age. The bone age in
GALE ENCYCLOPEDIA OF MEDICINE

Pituitary dwarfism

Cerebrum

Pineal gland

Cerebellum

Pituitary gland

Cerebral peduncle
Spinal cord

Pituitary dwarfism is a condition of growth retardation characterized by patients who are very short but have normal body
proportions. It is caused by a dysfunction of the pituitary gland, the pea-sized mass of tissue located at the base of the brain.
(Illustration by Electronic Illustrators Group.)

affected children is usually two years or more behind
the chronological age. This means that if a child is ten
years old, his or her bones will look like they are those
of an eight-year-old child. The levels of growth hormone and somatomedin C must also be measured with
blood tests.
Hypopituitarism may be gained or acquired following birth for several reasons. It could be due to
trauma to the pituitary gland such as a fall or following surgery to the brain for removal of a tumor. It may
also be due to the child’s environment (deprivational
dwarfism).
On examination by the doctor there may be optic
nerve atrophy, if the dwarfism is due to a type of
tumor. X rays of the area where the pituitary gland is
located (sella turcica) or more advanced imaging such
as magnetic resonance imaging (MRI) or computed
tomography CT may show changes of the pituitary
gland itself. Computed tomography, is an advanced
form of x ray that will help determine the integrity of
the bone and how much calcification the tumor is
producing. Magnetic resonance imaging, will also
GALE ENCYCLOPEDIA OF MEDICINE

help in the diagnosis. MRI is a type of imaging device
that can visualize soft tissues such as muscle and fat.
If the dwarfism is due to environmental and emotional problems, the individual may be hospitalization
to monitor hormone levels. Following a few days of
hospitalized, hormone levels may become normal due
to avoidance of the original environment.

Treatment
The main course of therapy is growth hormone
replacement therapy when there is lack of growth hormone in the body. A pediatric endocrinologist, a doctor specializing in the hormones of children, usually
administers this type of therapy before a child’s
growth plates have fused or joined together. Once the
growth plates have fused, GH replacement therapy is
rarely effective.
Growth hormone used to be collected from
recently deceased humans. However, frequent disease
complications resulting from human growth hormone
collected from deceased bodies, lead to the banning of
2911

Pituitary dwarfism

KEY TERMS
Adrenocorticotropin (corticotrophin)—A hormone that acts on cells of the adrenal cortex, causing them to produce male sex hormones and
hormones that control water and mineral balance
in the body.
Antidiuretic hormone (vasopressin)—A hormone
that acts on the kidneys to regulate water balance.
Craniopharyngioma—A tumor near the pituitary
gland in the craniopharyngeal canal that often
results in intracranial pressure.
Deprivational dwarfism—A condition where emotional disturbances are associated with growth failure and abnormalities of pituitary function.
Follicle-stimulating hormone (FSH)—A hormone
that in females stimulates estrogen and in males
stimulates sperm production.
Growth hormone—A hormone that eventually
stimulates growth. Also called somatotropin.
Hormone—A chemical messenger produced by
the body that is involved in regulating specific bodily functions such as growth, development, and
reproduction.
Luteinizing hormone—A hormone secreted by the
pituitary gland that regulates the menstrual cycle
and triggers ovulation in females. In males it stimulates the testes to produce testosterone.
Oxytocin—A hormone that stimulates the uterus to
contract during child birth and the breasts to
release milk.
Panhypopituitarism—Generalized decrease of all
of the anterior pituitary hormones.
Prolactin—A hormone that helps the breast prepare for milk production during pregnancy.
Puberty—Point in development when the gonads
begin to function and secondary sexual characteristics begin to appear.
Thyroid stimulating hormone (thyrotropin)—A
hormone that stimulates the thyroid gland to produce hormones that regulate metabolism.

this method. In the mid-1980s, techniques were discovered that could produce growth hormones in the
lab. Now, the only growth hormone used for treatment is that made in a laboratory.
A careful balancing of all of the hormones produced by the pituitary gland is necessary for patients
2912

with panhypopituitarism. This form of dwarfism is
very difficult to manage.

Prognosis
The prognosis for each type of dwarfism varies.
A panhypopituitarism dwarf does not pass through
the initial onset of adult sexual development (puberty)
and never produces enough gonadotropic hormones
to develop adult sexual function. These individuals
also have several other medical conditions. Dwarfism
due to only growth hormone deficiency has a different
prognosis. These individuals do pass through puberty
and mature sexually, however, they remain proportionately small in stature.
If the individual is lacking only growth hormone
then growth hormone replacement therapy can be
administered. The success of treatment with growth
hormone varies however. An increase in height of 4–6
in (10–15 cm) can occur in the first year of treatment.
Following this first year, the response to the hormone
is not as successful. Therefore the amount of growth
hormone administered must be tripled to maintain this
rate. Long-term use is considered successful if the
individual grows at least 0.75 in (2 cm) per year more
than they would without the hormone. However, if the
growth hormone treatment is not administered before
the long bones—such as the legs and arms—fuse, then
the individual will never grow. This fusion is completed by adult age.
Improvement for individuals with dwarfism due
to other causes such as a tumor, varies greatly. If the
dwarfism is due to deprevational causes, then removing a child from that environment should help to
alleviate the problem.
Resources
BOOKS

Beers, Mark H., Robert Berkow, and Mark Burs. ‘‘Pituitary
Dwarfism.’’ In MerckManual. Rahway, NJ: Merck &
Co., Inc., 2004.
ORGANIZATIONS

Human Growth Foundation. 997 Glen Cove Ave., Glen
Head, NY 11545. (800) 451-6434. Fax: (516) 671-4055.
<http://www.hgfound.org>.
Little People of America, Inc. National Headquarters, PO
Box 745, Lubbock, TX 79408. (806) 737-8186 or (888)
LPA-2001. lpadatabase@juno.com. <http://
www.lpaonline.org>.
OTHER

‘‘Clinical Growth Charts by the National Center for Health
Statistics.’’ Center for Disease Control. <http://
GALE ENCYCLOPEDIA OF MEDICINE

Jason S. Schliesser, DC

Pituitary gland removal see
Hypophysectomy

Pituitary tumors
Definition
Pituitary tumors are abnormal growths on the
pituitary gland. Some tumors secrete hormones normally made by the pituitary gland.

Description
Located in the center of the brain, the pituitary
gland manufactures and secretes hormones that
regulate growth, sexual development and functioning, and the fluid balance of the body. About 10%
of all cancers in the skull are pituitary tumors.
Pituitary adenomas (adenomas are tumors that
grow from gland tissues) and pituitary tumors in
children and adolescencents (craniopharyngiomas)
are the most common types of pituitary tumors.
They are usually benign and grow slowly. Even
malignant pituitary tumors rarely spread to other
parts of the body.
Pituitary adenomas do not secrete hormones but
are likely to be larger and more invasive than tumors
that do. Craniopharyngiomas are benign tumors that
are extremely difficult to remove. Radiation does not
stop them from spreading throughout the pituitary
gland. Craniopharyngiomas account for less than
5% of all brain tumors. Pituitary tumors usually
develop between the ages of 30 and 40, but half of all
craniopharyngiomas occur in children, with symptoms most often appearing between the ages of five
and ten.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The cause of pituitary tumors is not known, but
may be genetic. Symptoms related to tumor location,
size, and pressure on neighboring structures include:


persistent headache on one or both sides, or in the
center of the forehead



blurred or double vision; loss of peripheral vision



drooping eyelid caused by pressure on nerves leading
to the eye



seizures

Symptoms
include:

related

to

hormonal

imbalance



excessive sweating



loss of appetite



loss of interest in sex



inability to tolerate cold temperatures



nausea



high levels of sodium in the blood



menstrual problems



excessive thirst



frequent urination



dry skin



constipation



premature or delayed puberty



delayed growth in children



galactorrea (milk secretion in the absence of pregnancy or breast feeding)



low blood pressure



low blood sugar

Diagnosis
As many as 40% of all pituitary tumors do not
release excessive quantities of hormones into the
blood. Known as clinically nonfunctioning, these
tumors are difficult to distinguish from tumors that
produce similar symptoms. They may grow to be quite
large before they are diagnosed.
Endocrinologists and neuroendocrinologists base
the diagnosis of pituitary tumors on:


the patient’s own observations and medical history



physical examination



laboratory studies of the patient’s blood and cerebrospinal fluid
2913

Pituitary tumors

www.cdc.gov/nchs/about/major/nhanes/growthcharts/
clinical_charts.htm>.
‘‘Entry 312000: Panhypopituitarism; PHP.’’ OMIM—
Online Mendelian Inhericance in Man.. National
Institutes of Health. <http://www.ncbi.nlm.nih.gov/
htbin-post/Omim/dispmim?312000>.
Hill, Mark. ‘‘Development of the Endocrine System—
Pituitary.’’ The University of New South Wales, Sydney,
Australia—Department of Embryology. <http://anatomy.med.unsw.edu.au/CBL/Embryo/OMIMfind/
endocrine/pitlist.htm>.

Pityriasis rosea

KEY TERMS
Agonist—A drug that increases the effectiveness of
another drug.
Analogue—A drug that is similar to the drug from
which it is derived.

Colorized MRI showing large pituitary tumor at center in pink.
(Mehau Kulyk, Photo Researchers. Reproduced by permission.)



x rays of the skull and other studies that provide
images of the inside of the brain (CT, MRI)



vision tests



urinalysis

Treatment
Some pituitary tumors stabilize without treatment, but a neurosurgeon will operate at once to
remove the tumor (adenectomy) or pituitary gland
(hypophysectomy) of a patient whose vision is deteriorating rapidly. Patients who have pituitary apoplexy may experience very severe headaches, have
symptoms of stiff neck, and sensitivity to light. This
condition is considered an emergency. Magnetic
resonance imaging (MRI) is the best imaging technique for patients with these symptoms. If the tumor is
small, surgery may be done through the nose. If the
tumor is large, it may require opening the skull for
tumor removal. Selected patients do well with proton
beam radiosurgery (the use of high energy particles in
the form of a high energy beam to destroy an overactive gland).
Treatment is determined by the type of tumor and
by whether it has invaded tissues adjacent to the pituitary gland. Hormone-secreting tumors can be successfully treated with surgery, radiation, bromocriptine
(Parlodel), Sandostatin (Octreotide), or other somatostatin analogues (drugs similar to somatostatin).
Surgery is usually used to remove all or part of a
tumor within the gland or the area surrounding it,
and may be combined with radiation therapy to treat
tumors that extend beyond the pituitary gland.
Removal of the pituitary gland requires life-long hormone replacement therapy.
2914

Radiation therapy can provide long-term control
of the disease if it recurs after surgery, and radioactive
pellets can be implanted in the brain to treat craniopharyngiomas. CV205-502, a new dopamine agonist
(a drug that increases the effect of another, in this
instance dopamine) can control symptoms of patients
who do not respond to bromocriptine.

Prognosis
Pituitary tumors are usually curable. Following
surgery, adults may gradually resume their normal
activities, and children may return to school when
the effects of the operation have diminished, and appetite and sense of well-being have returned. Patients
should wear medical identification tags identifying
their condition and the hormonal replacement medicines they take.
Resources
ORGANIZATIONS

American Brain Tumor Association. 2770 River Road, Des
Plaines, IL 60018. (800) 886-2289. <http://
www.abta.org>.
Brain Tumor Information Services. Box 405, Room J341,
University of Chicago Hospitals, 5841 S. Maryland
Ave., Chicago, IL 60637. (312) 684-1400.

Maureen Haggerty

Pityriasis rosea
Definition
Pityriasis rosea is a mild, noncontagious skin disorder common among children and young adults, and
characterized by a single round spot on the body,
followed later by a rash of colored spots on the body
and upper arms.
GALE ENCYCLOPEDIA OF MEDICINE

Antihistamines—A group of drugs that block the
effects of histamine, a chemical released during an
allergic reaction.
Steroids—A group of drugs that includes the corticosteroids, similar to hormones produced by the
adrenal glands, and used to relieve inflammation
and itching.

Sometimes, before the symptoms appear, people
experience preliminary sensations including fever,
malaise, sore throat, or headache. Symptoms begin
with a single, large round spot called a ‘‘herald patch’’
on the body, followed days or weeks later by slightly
raised, scaly-edged round or oval pink-copper colored
spots on the trunk and upper arms. The spots, which
have a wrinkled center and a sharp border, sometimes
resemble a Christmas tree. They may be mild to severely
itchy, and they can spread to other parts of the body.

Diagnosis
A physician can diagnose the condition with
blood tests, skin scrapings, or a biopsy of the lesion.

Treatment
The torso of a man covered with pityriasis rosea. The cause of
this disorder is thought to be due to a viral infection. It often
appears on the torso and upper parts of the limbs of young
people and may be contagious. (Photograph by Dr. P. Marazzi,
Photo Researchers, Inc. Reproduced by permission.)

Description
Pityriasis rosea is most common in young adults,
and appears up to 50% more often in women. Its cause
is unknown; however, some scientists believe that the
rash is an immune response to some type of infection
in the body.

Causes and symptoms
Doctors do not think that pityriasis rosea is contagious, but the cause is unknown. Some experts suspect the rash, which is most common in spring and fall,
may be triggered by a virus, but no infectious agent has
ever been found.
It is not sexually transmitted, and does
not appear to be contagious from one person to the
next.
GALE ENCYCLOPEDIA OF MEDICINE

The rash usually clears up on its own, although a
physician should rule out other conditions that may
cause a similar rash (such as syphilis).
Treatment includes external and internal medications for itching and inflammation. Mild inflammation and itching can be relieved with antihistamine
drugs or calamine lotion, zinc oxide, or other mild
lubricants or anti-itching creams. Gentle, soothing
strokes should be used to apply the ointments, since
vigorous rubbing may cause the lesions to spread.
More severe itching and inflammation is treated with
topical steroids. Moderate exposure to sun or ultraviolet light may help heal the lesions, but patients
should avoid being sunburned.
Soap makes the rash more uncomfortable;
patients should bathe or shower with plain lukewarm
water, and apply a thin coating of bath oil to freshlydried skin afterwards.

Prognosis
These spots, which may be itchy, last for 3–12
weeks. Symptoms rarely recur.
2915

Pityriasis rosea

KEY TERMS

Placenta previa

Causes and symptoms

Resources
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.

Carol A. Turkington

PKU see Phenylketonuria

Placenta previa
Definition
Placenta previa is a condition that occurs during
pregnancy when the placenta is abnormally placed,
and partially or totally covers the cervix.

Description
The uterus is the muscular organ that contains the
developing baby during pregnancy. The lowest segment of the uterus is a narrowed portion called the
cervix. This cervix has an opening (the os) that leads
into the vagina, or birth canal. The placenta is the
organ that attaches to the wall of the uterus during
pregnancy. The placenta allows nutrients and oxygen
from the mother’s blood circulation to pass into the
developing baby (the fetus) via the umbilical cord.
During labor, the muscles of the uterus contract
repeatedly. This allows the cervix to begin to grow
thinner (called effacement) and more open (dilatation). Eventually, the cervix will become completely
effaced and dilated, and the baby can leave the uterus
and enter the birth canal. Under normal circumstances, the baby will emerge through the mother’s
vagina during birth.
In placenta previa, the placenta develops in an
abnormal location. Normally, the placenta should
develop relatively high up in the uterus, on the front
or back wall. In about one in 200 births, the placenta
will be located low in the uterus, partially or totally
covering the os. This causes particular problems in late
pregnancy, when the lower part of the uterus begins to
take on a new formation in preparation for delivery.
As the cervix begins to efface and dilate, the attachments of the placenta to the uterus are damaged,
resulting in bleeding.
2916

While the actual cause of placenta previa is
unknown, certain factors increase the risk of a
woman developing the condition. These factors
include:


having abnormalities of the uterus



being older in age



having had other babies



having a prior delivery by cesarean section



smoking cigarettes

When a pregnancy involves more than one baby
(twins, triplets, etc.), the placenta will be considerably
larger than for a single pregnancy. This also increases
the chance of placenta previa.
Placenta previa may cause a number of problems.
It is thought to be responsible for about 5% of all
miscarriages. It frequently causes very light bleeding
(spotting) early in pregnancy. Sometime after 28
weeks of pregnancy (most pregnancies last about 40
weeks), placenta previa can cause episodes of significant bleeding. Usually, the bleeding occurs suddenly
and is bright red. The woman rarely experiences any
accompanying pain, although about 10% of the time
the placenta may begin separating from the uterine
wall (called abruptio placentae), resulting in pain.
The bleeding usually stops on its own. About 25% of
such patients will go into labor within the next several
days. Sometimes, placenta previa does not cause
bleeding until labor has already begun.
Placenta previa puts both the mother and the fetus
at high risk. The mother is at risk of severe and
uncontrollable bleeding (hemorrhage), with dangerous
blood loss. If the mother’s bleeding is quite severe, this
puts the fetus at risk of becoming oxygen deprived. The
fetus’ only source of oxygen is the mother’s blood. The
mother’s blood loss, coupled with certain changes that
take place in response to that blood loss, decreases the
amount of blood going to the placenta, and ultimately
to the fetus. Furthermore, placenta previa increases the
risk of preterm labor, and the possibility that the baby
will be delivered prematurely.

Diagnosis
Diagnosis of placenta previa is suspected whenever bright red, painless vaginal bleeding occurs during the course of a pregnancy. The diagnosis can be
confirmed by performing an ultrasound examination.
This will allow the location of the placenta to be
evaluated.
GALE ENCYCLOPEDIA OF MEDICINE

Cesarean section—Delivery of a baby through an
incision in the mother’s abdomen instead of
through the vagina.
Labor—The process during which the uterus contracts, and the cervix opens to allow the passage of a
baby into the vagina.
Placenta—The organ that provides oxygen and
nutrition from the mother to the baby during pregnancy. The placenta is attached to the wall of the
uterus and leads to the baby via the umbilical cord.
Umbilical cord—The blood vessels that allow the
developing baby to receive nutrition and oxygen
from its mother; the blood vessels also eliminate
the baby’s waste products. One end of the umbilical cord is attached to the placenta and the other
end is attached to the baby’s belly button
(umbilicus).
Vagina—The birth canal; the passage from the cervix of the uterus to the opening leading outside of a
woman’s body.

almost always the preferred method of delivery in
order to avoid further bleeding from the low-lying
placenta.

Prognosis
In cases of placenta previa, the prognosis for the
mother is very good. However, there is a 15–20%
chance the infant will not survive. This is 10 times
the death rate associated with normal pregnancies.
About 60% of these deaths occur because the baby
delivered was too premature to survive.

Prevention
There are no known ways to insure the appropriate placement of the placenta in the uterus. However,
careful treatment of the problem can result in the best
chance for a good outcome for both mother and baby.
Resources
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th Street, S.W., P.O. Box 96920, Wasington, DC
20090-6920. .

Rosalyn Carson-DeWitt, MD
While many conditions during pregnancy require
a pelvic examination, in which the health care provider’s fingers are inserted into the patient’s vagina, such
an examination should never be performed if there is
any suspicion of placenta previa. Such an examination
can disturb the already susceptible placenta, resulting
in hemorrhage.
Sometimes placenta previa is found early in a
pregnancy, during an ultrasound examination
performed for another reason. In these cases, it is
wise to have a repeat ultrasound performed later in
pregnancy (during the last third of the pregnancy,
called the third trimester). A large percentage of
these women will have a low-lying placenta, but not
a true placenta previa where some or all of the os is
covered.

Treatment
Treatment depends on how far along in the pregnancy the bleeding occurs. When the pregnancy is less
than 36 weeks along, the fetus is not sufficiently developed to allow delivery without a high risk of complications. Therefore, a woman with placenta previa is
treated with bed rest, blood transfusions as necessary,
and medications to prevent labor. After 36 weeks, the
baby can be delivered via cesarean section. This is
GALE ENCYCLOPEDIA OF MEDICINE

Placental abruption
Definition
Placental abruption occurs when the placenta
separates from the wall of the uterus prior to the
birth of the baby. This can result in severe, uncontrollable bleeding (hemorrhage).

Description
The uterus is the muscular organ that contains the
developing baby during pregnancy. The lowest segment of the uterus is a narrowed portion called the
cervix. This cervix has an opening (the os) that leads
into the vagina, or birth canal. The placenta is the
organ that attaches to the wall of the uterus during
pregnancy. The placenta allows nutrients and oxygen
from the mother’s blood circulation to pass into the
developing baby (the fetus) via the umbilical cord.
During labor, the muscles of the uterus contract
repeatedly. This allows the cervix to begin to grow
thinner (called effacement) and more open
2917

Placental abruption

KEY TERMS

Placental abruption

(dilatation). Eventually, the cervix will become completely effaced and dilated, and the baby can leave the
uterus and enter the birth canal. Under normal circumstances, the baby will go through the mother’s
vagina during birth.
During a normal labor and delivery, the baby is
born first. Several minutes to 30 minutes later, the
placenta separates from the wall of the uterus and is
delivered. This sequence is necessary because the baby
relies on the placenta to provide oxygen until he or she
begins to breathe independently.
Placental abruption occurs when the placenta
separates from the uterus before the birth of the
baby. Placental abruption occurs in about one out of
every 200 deliveries. African-American and LatinAmerican women have a greater risk of this complication than do Caucasian women. It was once believed
that the risk of placental abruption increased in
women who gave birth to many children, but this
association is still being researched.

Causes and symptoms
The cause of placental abruption is unknown.
However, a number of risk factors have been identified. These factors include:


older age of the mother



history of placental abruption during a previous
pregnancy



high blood pressure



certain disease states (diabetes, collagen vascular
diseases)



the presence of a type of uterine tumor called a
leiomyoma



twins, triplets, or other multiple pregnancies



cigarette smoking



heavy alcohol use



cocaine use



malformations of the uterus



malformations of the placenta



injury to the abdomen (as might occur in a car
accident)

Symptoms of placental abruption include bleeding from the vagina, severe pain in the abdomen or
back, and tenderness of the uterus. Depending on the
severity of the bleeding, the mother may experience a
drop in blood pressure, followed by symptoms of
organ failure as her organs are deprived of oxygen.
Sometimes, there is no visible vaginal bleeding.
2918

Instead, the bleeding is said to be ‘‘concealed.’’ In
this case, the bleeding is trapped behind the placenta,
or there may be bleeding into the muscle of the uterus.
Many patients will have abnormal contractions of the
uterus, particularly extremely hard, prolonged contractions. Placental abruption can be total (in which
case the fetus will almost always die in the uterus), or
partial.
Placental abruption can also cause a very serious
complication called consumptive coagulopathy. A series of reactions begin that involve the elements of the
blood responsible for clotting. These clotting elements
are bound together and used up by these reactions.
This increases the risk of uncontrollable bleeding and
may contribute to severe bleeding from the uterus, as
well as causing bleeding from other locations (nose,
urinary tract, etc.).
Placental abruption is risky for both the mother
and the fetus. It is dangerous for the mother because of
blood loss, loss of clotting ability, and oxygen deprivation to her organs (especially the kidneys and heart).
This condition is dangerous for the fetus because of
oxygen deprivation, too, since the mother’s blood is
the fetus’ only source of oxygen. Because the abrupting placenta is attached to the umbilical cord, and the
umbilical cord is an extension of the fetus’ circulatory
system, the fetus is also at risk of hemorrhaging. The
fetus may die from these stresses, or may be born with
damage due to oxygen deprivation. If the abruption
occurs well before the baby was due to be delivered,
early delivery may cause the baby to suffer complications of premature birth.

Diagnosis
Diagnosis of placental abruption relies heavily on
the patient’s report of her symptoms and a physical
examination performed by a health care provider.
Ultrasound can sometimes be used to diagnose an
abruption, but there is a high rate of missed or incorrect diagnoses associated with this tool when used for
this purpose. Blood will be taken from the mother and
tested to evaluate the possibility of life-threatening
problems with the mother’s clotting system.

Treatment
The first line of treatment for placental abruption
involves replacing the mother’s lost blood with blood
transfusions and fluids given through a needle in a
vein. Oxygen will be administered, usually by a mask
or through tubes leading to the nose. When the placental separation is severe, treatment may require
GALE ENCYCLOPEDIA OF MEDICINE

Cesarean section—Delivery of a baby through an
incision in the mother’s abdomen, instead of
through the vagina.
Labor—The process during which the uterus contracts, and the cervix opens to allow the passage of a
baby into the vagina.
Placenta—The organ that provides oxygen and
nutrition from the mother to the baby during pregnancy. The placenta is attached to the wall of the
uterus and leads to the baby via the umbilical cord.
Umbilical cord—The blood vessels that allow the
developing baby to receive nutrition and oxygen
from its mother; the blood vessels also eliminate
the baby’s waste products. One end of the umbilical cord is attached to the placenta and the other
end is attached to the baby’s belly button
(umbilicus).
Uterus—The muscular organ that contains the
developing baby during pregnancy.
Vagina—The birth canal; the passage from the cervix of the uterus to the opening leading outside of a
woman’s body.

prompt delivery of the baby. However, delivery may
be delayed when the placental separation is not as
severe, and when the fetus is too immature to insure
a healthy baby if delivered. The baby is delivered
vaginally when possible. However, a cesarean section
may be performed to deliver the baby more quickly if
the abruption is quite severe or if the baby is in
distress.

Prognosis
The prognosis for cases of placental abruption
varies, depending on the severity of the abruption.
The risk of death for the mother ranges up to 5%,
usually due to severe blood loss, heart failure, and
kidney failure. In cases of severe abruption, 50–80%
of all fetuses die. Among those who survive, nearly
half will have lifelong problems due to oxygen deprivation in the uterus and premature birth.

Prevention
Some of the causes of placental abruption are
preventable. These include cigarette smoking, alcohol
abuse, and cocaine use. Other causes of abruption may
GALE ENCYCLOPEDIA OF MEDICINE

not be avoidable, like diabetes or high blood pressure.
These diseases should be carefully treated. Patients
with conditions known to increase the risk of placental
abruption should be carefully monitored for signs and
symptoms of this complication.
Resources
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th Street, S.W., P.O. Box 96920, Washington, DC
20090-6920.

Rosalyn Carson-DeWitt, MD

Plague
Definition
Plague is a serious, potentially life-threatening
infectious disease that is usually transmitted to
humans by the bites of rodent fleas. It was one of the
scourges of early human history. There are three
major forms of the disease: bubonic, septicemic, and
pneumonic.

Description
Plague has been responsible for three great world
pandemics, which caused millions of deaths and significantly altered the course of history. A pandemic is
a disease occurring in epidemic form throughout the
entire population of a country, a people, or the world.
Although the cause of the plague was not identified
until the third pandemic in 1894, scientists are virtually
certain that the first two pandemics were plague
because a number of the survivors wrote about their
experiences and described the symptoms.
The first great pandemic appeared in AD 542 and
lasted for 60 years. It killed millions of citizens, particularly people living along the Mediterranean Sea.
This sea was the busiest, coastal trade route at that
time and connected what is now southern Europe,
northern Africa, and parts of coastal Asia. This pandemic is sometimes referred to as the Plague of
Justinian, named for the great emperor of Byzantium
who was ruling at the beginning of the outbreak.
According to the historian Procopius, this outbreak
of plague killed 10,000 people per day at its height just
within the city of Constantinople.
2919

Plague

KEY TERMS

Plague

The second pandemic occurred during the fourteenth century, and was called the Black Death because
its main symptom was the appearance of black patches
(caused by bleeding) on the skin. It was also a subject
found in many European paintings, drawings, plays,
and writings of that time. The connections between
large active trading ports, rats coming off the ships,
and the severe outbreaks of the plague were understood
by people at the time. This was the most severe of the
three, beginning in the mid-1300s with an origin in central Asia and lasting for 400 years. Between a fourth and
a third of the entire European population died within a
few years after plague was first introduced. Some smaller
villages and towns were completely wiped out.
The final pandemic began in northern China,
reaching Canton and Hong Kong by 1894. From
there, it spread to all continents, killing millions.
The great pandemics of the past occurred when
wild rodents spread the disease to rats in cities, and
then to humans when the rats died. Another route for
infection came from rats coming off ships that had
traveled from heavily infected areas. Generally, these
were busy coastal or inland trade routes. Plague was
introduced into the United States during this pandemic and it spread from the West towards the
Midwest and became endemic in the Southwest of
the United States.
About 10–15 Americans living in the southwestern
United States contract plague each year during the
spring and summer. The last rat-borne epidemic in the
United States occurred in Los Angeles in 1924–25.
Since then, all plague cases in this country have been
sporadic, acquired from wild rodents or their fleas.
Plague can also be acquired from ground squirrels
and prairie dogs in parts of Arizona, New Mexico,
California, Colorado, and Nevada. Around the world,
there are between 1,000 and 2,000 cases of plague each
year. Recent outbreaks in humans occurred in Africa,
South America, and Southeast Asia.
Some people and/or animals with bubonic plague
go on to develop pneumonia (pneumonic plague). This
can spread to others via infected droplets during
coughing or sneezing.
Plague is one of three diseases still subject to
international health regulations. These rules require
that all confirmed cases be reported to the World
Health Organization (WHO) within 24 hours of diagnosis. According to the regulations, passengers on an
international voyage who have been to an area where
there is an epidemic of pneumonic plague must be
placed in isolation for six days before being allowed
to leave.
2920

While plague is found in several countries, there is
little risk to United States travelers within endemic
areas (limited locales where a disease is known to be
present) if they restrict their travel to urban areas with
modern hotel accommodations.
Over the past few years, this infection primarily of
antiquity has become a modern issue. This change has
occurred because of the concerns about the use of
plague as a weapon of biological warfare or terrorism
(bioterrorism). Along with anthrax and smallpox, plague is considered to be a significant risk. In this scenario, the primary manifestation is likely to be
pneumonic plague transmitted by clandestine aerosols. It has been reported that during World War II
the Japanese dropped ‘‘bombs’’ containing plagueinfected fleas in China as a form of biowarfare.

Causes and symptoms
Fleas carry the bacterium Yersinia pestis, formerly
known as Pasteurella pestis. The plague bacillus can be
stained with Giemsa stain and typically looks like a
safety pin under the microscope. When a flea bites an
infected rodent, it swallows the plague bacteria. The
bacteria are passed on when the fleas, in turn, bite a
human. Interestingly, the plague bacterium grows in
the gullet of the flea, obstructing it and not allowing
the flea to eat. Transmission occurs during abortive
feeding with regurgitation of bacteria into the feeding
site. Humans also may become infected if they have a
break or cut in the skin and come in direct contact with
body fluids or tissues of infected animals.
More than 100 species of fleas have been reported
to be naturally infected with plague; in the western
United States, the most common source of plague is
the golden-manteled ground squirrel flea. Chipmunks
and prairie dogs have also been identified as hosts of
infected fleas.
Since 1924, there have been no documented cases
in the United States of human-to-human spread of
plague from droplets. All but one of the few pneumonic cases have been associated with handling infected
cats. While dogs and cats can become infected, dogs
rarely show signs of illness and are not believed to
spread disease to humans. However, plague has been
spread from infected coyotes (wild dogs) to humans.
In parts of central Asia, gerbils have been identified as
the source of cases of bubonic plague in humans.
Bubonic plague
Two to five days after infection, patients experience a sudden fever, chills, seizures, and severe
GALE ENCYCLOPEDIA OF MEDICINE

Plague

Rats

Squirrels

Yersinia pestis

Flea
Figure A

Gophers
Figure B

Figure C

Plague is a serious infectious disease transmitted by the bites of rat fleas. There are three major forms of plague: bubonic,
pneumonic, and septicemic. As illustrated above, fleas carry the bacterium Yersinia pestis. When a flea bites an infected rodent,
it becomes a vector and then passes the plague bacteria when it bites a human. (Illustration by Electronic Illustrators Group.)

headaches, followed by the appearance of swellings or
‘‘buboes’’ in armpits, groin, and neck. The most commonly affected sites are the lymph glands near the site
of the first infection. As the bacteria multiply in the
glands, the lymph node becomes swollen. As the nodes
collect fluid, they become extremely tender.
Occasionally, the bacteria will cause an ulcer at the
point of the first infection.

in the phlegm. If untreated, half the patients will die; if
blood poisoning occurs as an early complication,
patients may die even before the buboes appear.
Life-threatening complications of plague include
shock, high fever, problems with blood clotting, and
convulsions.

Diagnosis
Septicemic plague
Bacteria that invade the bloodstream directly
(without involving the lymph nodes) cause septicemic
plague. (Bubonic plague also can progress to septicemic plague if not treated appropriately.) Septicemic
plague that does not involve the lymph glands is particularly dangerous because it can be hard to diagnose
the disease. The bacteria usually spread to other sites,
including the liver, kidneys, spleen, lungs, and sometimes the eyes, or the lining of the brain. Symptoms
include fever, chills, prostration, abdominal pain,
shock, and bleeding into the skin and organs.
Pneumonic plague
Pneumonic plague may occur as a direct infection
(primary) or as a result of untreated bubonic or septicemic plague (secondary). Primary pneumonic plague
is caused by inhaling infective drops from another
person or animal with pneumonic plague.
Symptoms, which appear within one to three days
after infection, include a severe, overwhelming pneumonia, with shortness of breath, high fever, and blood
GALE ENCYCLOPEDIA OF MEDICINE

Plague should be suspected if there are painful
buboes, fever, exhaustion, and a history of possible
exposure to rodents, rabbits, or fleas in the West or
Southwest. The patient should be isolated. Chest x
rays are taken, as well as blood cultures, antigen testing, and examination of lymph node specimens. Blood
cultures should be taken 30 minutes apart, before
treatment.
A group of German researchers reported in 2004
on a standardized enzyme-linked immunosorbent
assay (ELISA) kit for the rapid diagnosis of plague.
The test kit was developed by the German military and
has a high degree of accuracy as well as speed in
identifying the plague bacillus. The kit could be useful
in the event of a bioterrorist attack as well as in countries without advanced microbiology laboratories.

Treatment
As soon as plague is suspected, the patient should
be isolated, and local and state departments notified.
Drug treatment reduces the risk of death to less
2921

dust and kept indoors. Handling sick or dead animals
(especially rodents and cats) should be avoided.

Bioterrorism—The use of disease agents to terrorize or intimidate a civilian population.
Buboes—Smooth, oval, reddened, and very painful
swellings in the armpits, groin, or neck that occur as
a result of infection with the plague.

Plague vaccines have been used with varying effectiveness since the late nineteenth century. Experts
believe that vaccination lowers the chance of infection
and the severity of the disease. However, the effectiveness of the vaccine against pneumonic plague is not
clearly known.

Plague

KEY TERMS

Endemic—A disease that occurs naturally in a geographic area or population group.
Epidemic—A disease that occurs throughout part of
the population of a country.
Pandemic—A disease that occurs throughout a
regional group, the population of a country, or the
world.
Septicemia—The medical term for blood poisoning, in which bacteria have invaded the bloodstream and circulates throughout the body.

than 5%. The preferred treatment is streptomycin
administered as soon as possible. Alternatives include
gentamicin, chloramphenicol, tetracycline, or trimethoprim/sulfamethoxazole.

Prognosis
Plague can be treated successfully if it is caught
early; the mortality rate for treated disease is 1–15%
but 40–60% in untreated cases. Untreated pneumonic
plague is almost always fatal, however, and the
chances of survival are very low unless specific antibiotic treatment is started within 15–18 hours after
symptoms appear. The presence of plague bacteria in
a blood smear is a grave sign and indicates septicemic
plague. Septicemic plague has a mortality rate of 40%
in treated cases and 100% in untreated cases.

Prevention
Anyone who has come in contact with a plague
pneumonia victim should be given antibiotics, since
untreated pneumonic plague patients can pass on their
illness to close contacts throughout the course of the
illness. All plague patients should be isolated for 48
hours after antibiotic treatment begins. Pneumonic
plague patients should be completely isolated until
sputum cultures show no sign of infection.
Residents of areas where plague is found should
keep rodents out of their homes. Anyone working in a
rodent-infested area should wear insect repellent on
skin and clothing. Pets can be treated with insecticidal
2922

Vaccinations against plague are not required to
enter any country. Because immunization requires
multiple doses over a 6–10 month period, plague
vaccine is not recommended for quick protection
during outbreaks. Moreover, its unpleasant side
effects make it a poor choice unless there is a substantial long-term risk of infection. The safety of the
vaccine for those under age 18 has not been established. Pregnant women should not be vaccinated
unless the need for protection is greater than the
risk to the unborn child. Even those who receive the
vaccine may not be completely protected. The inadequacy of the vaccines available as of the early 2000s
explains why it is important to protect against
rodents, fleas, and people with plague. A team of
researchers in the United Kingdom reported in the
summer of 2004 that an injected subunit vaccine is
likely to offer the best protection against both bubonic and pneumonic forms of plague.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Plague (Bubonic Plague; Pestis; Black Death).’’ In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Davis, S., M. Begon, L. DeBruyn, et al. ‘‘Predictive
Thresholds for Plague in Kazakhstan.’’ Science 304
(April 30, 2004): 736–738.
Gani, R., and S. Leach. ‘‘Epidemiologic Determinants for
Modeling Pneumonic Plague Outbreaks.’’ Emerging
Infectious Diseases 10 (April 2004): 608–614.
Splettstoesser, W. D., L. Rahalison, R. Grunow, et al.
‘‘Evaluation of a Standardized F1 Capsular Antigen
Capture ELISA Test Kit for the Rapid Diagnosis of
Plague.’’ FEMS Immunology and Medical Microbiology
41 (June 1, 2004): 149–155.
Titball, R. W., and E. D. Williamson. ‘‘Yersinia pestis
(Plague) Vaccines.’’ Expert Opinion on Biological
Therapy 4 (June 2004): 965–973.
Velendzas, Demetres, MD, and Susan Dufel, MD.
‘‘Plague.’’ eMedicine December 2, 2004. <http://
www.emedicine.com/EMERG/topic428.htm>.
GALE ENCYCLOPEDIA OF MEDICINE

Centers for Disease Control. 1600 Clifton Rd., NE, Atlanta,
GA 30333. (800) 311-3435, (404) 639-3311. <http://
www.cdc.gov>.
National Institute of Allergies and Infectious Diseases,
Division of Microbiology and Infectious Diseases.
Bldg. 31, Rm. 7A-50, 31 Center Drive MSC 2520,
Bethesda, MD 20892.
World Health Organization. Division of Emerging and
Other Communicable Diseases Surveillance and
Control. 1211 Geneva 27, Switzerland.
OTHER

Bacterial Diseases (Healthtouch). <http://www.healthtouch.com/level1/leaflets/105825/105826.htm>.
Bug Bytes. <http://www.isumc.edu/bugbytes/>.
Centers for Disease Control. <http://www.cdc.gov/travel/
travel.html>.
Infectious Diseases Weblink. <http://pages.prodigy.net/
pdeziel/>.
International Society of Travel Medicine. <http://
www.istm.org>.
World Health Organization. <http://www.who.ch/>.

Arnold Cua, MD
Rebecca J. Frey, PhD

Plaque see Skin lesions
Plasma cell myeloma see Multiple myeloma

Plasma renin activity
Definition
Renin is an enzyme released by the kidney to help
control the body’s sodium-potassium balance, fluid
volume, and blood pressure.

Purpose
Plasma renin activity (PRA), also called plasma
renin assay, may be used to screen for high blood
pressure (hypertension) of kidney origin, and may
help plan treatment of essential hypertension, a
genetic disease often aggravated by excess sodium
intake. PRA is also used to further evaluate a diagnosis of excess aldosterone, a hormone secreted by the
adrenal cortex, in a condition called Conn’s syndrome.

Precautions
Patients taking diuretics, antihypertensives, vasodilators, oral contraceptives, and licorice should discontinue use of these substances for two to four
GALE ENCYCLOPEDIA OF MEDICINE

weeks before the test. It should be noted that renin
is increased in pregnancy and in diets with reduced
salt intake. Also, since renin is affected by body position, as well as by diurnal (daily) variation, blood
samples should be drawn in the morning, and the
position of the patient (sitting or lying down) should
be noted.

Description
When the kidneys release the enzyme renin in
response to certain conditions (high blood potassium,
low blood sodium, decreased blood volume), it is the
first step in what is called the renin-angiotensin-aldosterone cycle. This cycle includes the conversion of
angiotensinogen to angiotensin I, which in turn is
converted to angiotensin II, in the lung. Angiotensin
II is a powerful blood vessel constrictor, and its action
stimulates the release of aldosterone from an area of
the adrenal glands called the adrenal cortex. Together,
angiotensin and aldosterone increase the blood
volume, the blood pressure, and the blood sodium to
re-establish the body’s sodium-potassium and fluid
volume balance. Primary aldosteronism, the symptoms of which include hypertension and low blood
potassium (hypokalemia), is considered ‘‘low-renin
aldosteronism.’’
Renin itself is not actually measured in the PRA
test, because renin can be measured only with great
difficulty even in research laboratories. In the most
commonly used renin assay, the test actually determines, by a procedure called radioimmunoassay, the
rate of angiotensin I generation per unit time, while
the PRC (plasma renin concentration) measures the
maximum renin effect.
Both the PRA and the PRC are extremely difficult
to perform. Not only is renin itself unstable, but the
patient’s body position and the time of day affect the
results. Also, the sample must be collected properly:
drawn into a chilled syringe and collection tube,
placed on ice, and sent to the performing laboratory
immediately. Even if all these procedures are followed,
results can vary significantly.
A determination of the PRA and a measurement
of the plasma aldosterone level are used in the
differential diagnosis of primary and secondary
hyperaldosteronism. Patients with primary hyperaldosteronism (caused by an adrenal tumor that overproduces aldosterone) will have an increased
aldosterone level with decreased renin activity.
Conversely, patients with secondary hyperaldosteronism (caused by certain types of kidney disease) will
have increased levels of renin.
2923

Plasma renin activity

ORGANIZATIONS

Plasma renin activity

KEY TERMS
Aldosteronism—A disorder caused by excessive
production of the hormone aldosterone, which is
produced by a part of the adrenal glands called the
adrenal cortex. Causes include a tumor of the adrenal gland (Conn’s syndrome), or a disorder reducing the blood flow through the kidney. This leads
to overproduction of renin and angiotensin, and in
turn causes excessive aldosterone production.
Symptoms include hypertension, impaired kidney
function, thirst and muscle weakness.
Conn’s syndrome—A disorder caused by excessive
aldosterone secretion by a benign tumor of one of
the adrenal glands. This results in malfunction of
the body’s salt and water balance and subsequently
causes hypertension. Symptoms include thirst,
muscle weakness, and excessive urination.

Renin stimulation test
The renin stimulation test is performed to help
diagnose and distinguish the two forms of hyperaldosteronism. With the patient having been on a low-salt
diet and lying down for the test, a blood sample for
PRA is obtained. The PRA is repeated with the patient
still on the low salt diet but now standing upright. In
cases of primary hyperaldosteronism, the blood
volume is greatly expanded, and a change in position
or reduced salt intake does not result in decreased
kidney blood flow or decreased blood sodium. As a
result, renin levels do not increase. However, in secondary hyperaldosteronism, blood sodium levels
decrease with a lowered salt intake, and when the
patient is standing upright, the kidney blood flow
decreases as well. Consequently, renin levels do
increase.
Captopril test
The captopril test is a screening test for hypertension of kidney origin (renovascular hypertension). For
this test, a baseline PRA test is done first, then the
patient receives an oral dose of captopril, which is an
angiotensin-converting enzyme (ACE) inhibitor.
Blood pressure measurements are taken at this time
and again at 60 minutes when another PRA test is
done. Patients with kidney-based hypertension
demonstrate greater falls in blood pressure and
increases in PRA after captopril administration
2924

than do those with essential hypertension.
Consequently, the captopril test is an excellent
screening procedure to determine the need for a
more invasive radiographic evaluation such as renal
arteriography.

Preparation
This test requires a blood sample. For the PRA,
the patient should maintain a normal diet with a
restricted amount of sodium (approximately 3 g per
day) for three days before the test. It is recommended
that the patient be fasting (nothing to eat or drink)
from midnight the day of the test.

Risks
Risks for this test are minimal, but may
include slight bleeding from the puncture site,
fainting or feeling lightheaded after venipuncture,
or hematoma (blood accumulating under the puncture site).

Normal results
Reference values for the PRA test are laboratory-specific and depend upon the kind of diet
(sodium restricted or normal), the age of the patient,
and the patient’s posture at the time of the test.
Values are also affected if renin has been stimulated
or if the patient has received an ACE inhibitor, like
captopril.

Abnormal results
Increased PRA levels are seen in essential hypertension (uncommon), malignant hypertension, and
kidney-based (renovascular) hypertension. Reninproducing renal tumors, while rare, can also cause
elevated levels, as can cirrhosis, low blood volume
due to hemorrhage, and diminished adrenal function
(Addison’s disease). Decreased renin levels may indicate increased blood volume due to a high-sodium
diet, salt-retaining steroids, primary aldosteronism,
licorice ingestion syndrome, or essential hypertension
with low renin levels.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnosticand
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores
GALE ENCYCLOPEDIA OF MEDICINE

Three procedures are available:

Definition
Plasmapheresis is a blood purification procedure
used to treat several autoimmune diseases. It is also
known as therapeutic plasma exchange.

Purpose
In an autoimmune disease, the immune system
attacks the body’s own tissues. In many autoimmune
diseases, the chief weapons of attack are antibodies,
proteins that circulate in the bloodstream until they
meet and bind with the target tissue. Once bound, they
impair the functions of the target, and signal other
immune components to respond as well.
Plasmapheresis is used to remove antibodies from
the bloodstream, thereby preventing them from
attacking their targets. It does not directly affect the
immune system’s ability to make more antibodies, and
therefore may only offer temporary benefit. This procedure is most useful in acute, self-limited disorders
such as Guillain-Barré syndrome, or when chronic
disorders, such as myasthenia gravis, become more
severe in symptoms. In these instances, a rapid
improvement could save the patient’s life. Neurologic
diseases comprise 90% of the diseases that could profit
from plasmapheresis.

Precautions
Patients with clotting disorders may not be suitable candidates for plasmapheresis.



‘‘Discontinuous flow centrifugation.’’ Only one
venous catheter line is required. Approximately 300
ml of blood is removed at a time and centrifuged to
separate plasma from blood cells.



‘‘Continuous flow centrifugation.’’ Two venous lines
are used. This method requires slightly less blood
volume to be out of the body at any one time.



‘‘Plasma filtration.’’ Two venous lines are used. The
pasma is filtered using standard hemodialysis equipment. It requires less than 100 ml of blood to be
outside the body at one time.

A single plasmapheresis session may be effective,
although it is more common to have several sessions
per week over the course of two weeks or more.

Preparation
Good nutrition and plenty of rest make the
procedure less stressful. The treating physician
determines which of the patient’s medications
should be discontinued before the plasmapheresis
session.

Aftercare
The patient may experience dizziness, nausea,
numbness, tingling, or lightheadedness during or
after the procedure. These effects usually pass quickly,
allowing the patient to return to normal activities the
same day.

Description
The basic procedure consists of removal of blood,
separation of blood cells from plasma, and return of
these blood cells to the body’s circulation, diluted with
fresh plasma or a substitute. Because of concerns over
viral infection and allergic reaction, fresh plasma is not
routinely used. Instead, the most common substitute is
saline solution with sterilized human albumin protein.
During the course of a single session, two to three liters
of plasma is removed and replaced.
Plasmapheresis requires insertion of a venous
catheter, either in a limb or central vein. Central
veins allow higher flow rates and are more convenient
for repeat procedures, but are more often the site of
complications, especially bacterial infection.
When blood is outside the body, it must be treated
to prevent it from clotting. While most of the
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Reinfusion (replacement) with human plasma
may cause anaphylaxis, a life threatening allergic reaction. All procedures may cause a mild allergic reaction, leading to fever, chills, and rash. Bacterial
infection is a risk, especially when a central venous
catheter is used. Reaction to the citrate anticoagulant
used may cause cramps and numbness, though these
usually resolve on their own. Patients with impaired
kidney function may require drug treatment for the
effects of citrate metabolism.
Plasma contains clotting agents, chemicals that
allow the blood to coagulate into a solid clot. Plasma
exchange removes these. Bleeding complications are
rare following plasmapheresis, but may require replacement of clotting factors.
2925

Plasmapheresis

Plasmapheresis

anticlotting agent is removed from the blood during
treatment, some is returned to the patient.

Plastic, cosmetic, and reconstructive surgery

Resources

KEY TERMS
Anaphylaxis—Also called anaphylactic shock, it is
a severe allergic reaction to a foreign substance that
the patient has had contact with. Penicillin is an
example of a substance that causes severe allergic
reactions for some people.
Antibody—Chemicals produced by the body to
defend it against bacteria, viruses, or other cells
foreign to the body (antigens). Each specific antibody reacts against a specific foreign body.
Antibodies are also termed immunoglobulins.
Autoimmune—Autoimmune refers to the body’s
development of intolerance of the antigens on its
own cells.
Hemodialysis—A method to take out unwanted
parts of the blood. The patient’s blood is run
through a catheter and tubing into a machine called
a dialyzer, which filters out the unwanted blood
component.
Plasma—Plasma makes up 50% of human blood. It
is a watery fluid that carries red cells, white cells,
and platelets throughout the body.

Normal results
Plasmapheresis is an effective temporary treatment for:


Guillain-Barré syndrome (an acute neurological disorder following a viral infection that produces progressive muscle weakness and paralysis)



Myasthenia gravis (an autoimmune disease that
causes muscle weakness)



chronic inflammatory demyelinating polyneuropathy (a chronic neurological disorder caused by
destruction of the myelin sheath of peripheral nerves,
which produces symptoms similar to Guillain-Barré
syndrome)



thrombotic thrombocytopenic purpura (a rare blood
disorder)



Paraproteinemic peripheral neuropathies (a neurological disorder affecting the peripheral nerves)



blood that is too thick (hyperviscosity)

Other conditions may respond to plasmapheresis
as well. Beneficial effects are usually seen within several days. Effects commonly last up to several months,
although longer-lasting changes are possible, presumably by inducing shifts in immune response.
2926

BOOKS

Samuels, Martin, and Steven Feske, editors. Office Practice
of Neurology. New York: Churchill Livingstone, 1996.

Richard Robinson

Plasmodium infection see Malaria

Plastic, cosmetic, and reconstructive surgery
Definition
Plastic, cosmetic, and reconstructive surgery
refers to a variety of operations performed in order
to repair or restore body parts to look normal, or to
change a body part to look better. These types of
surgery are highly specialized. They are characterized
by careful preparation of the patient’s skin and tissues,
by precise cutting and suturing techniques, and by care
taken to minimize scarring. Recent advances in the
development of miniaturized instruments, new materials for artificial limbs and body parts, and improved
surgical techniques have expanded the range of plastic
surgery operations that can be performed.

Purpose
Although these three types of surgery share some
common techniques and approaches, they have somewhat different emphases. Plastic surgery is usually
performed to treat birth defects and to remove skin
blemishes such as warts, acne scars, or birthmarks.
Cosmetic surgery procedures are performed to make
the patient look younger or enhance his or her appearance in other ways. Reconstructive surgery is used to
reattach body parts severed in combat or accidents, to
perform skin grafts after severe burns, or to reconstruct parts of the patient’s body that were missing at
birth or removed by surgery. Reconstructive surgery is
the oldest form of plastic surgery, having developed
out of the need to treat wounded soldiers in wartime.

Precautions
Medical
Some patients should not have plastic surgery
because of certain medical risks. These groups include:
GALE ENCYCLOPEDIA OF MEDICINE

Plastic, cosmetic, and reconstructive surgery

A patient undergoing abdominoplasty. (Photo Researchers, Inc. Reproduced by permission)



patients recovering from a heart attack, severe infection (for example, pneumonia), or other serious
illness



patients with infectious hepatitis or HIV infection



cancer patients
(metastasize)



patients who are extremely overweight. Patients who
are more than 30% overweight should not have
liposuction



whose

cancer

might

spread

patients with blood clotting disorders
Psychological

Plastic, cosmetic, and reconstructive surgeries
have an important psychological dimension because
of the high value placed on outward appearance in
Western society. Many people who are born with
visible deformities or disfigured by accidents later in
life develop emotional problems related to social rejection. Other people work in fields such as acting, modeling, media journalism, and even politics, where their
employment depends on how they look. Some people
have unrealistic expectations of cosmetic surgery and
GALE ENCYCLOPEDIA OF MEDICINE

think that it will solve all their life problems. It is
important for anyone considering nonemergency plastic or cosmetic surgery to be realistic about its results.
One type of psychiatric disorder, called body dysmorphic disorder, is characterized by an excessive preoccupation with imaginary or minor flaws in
appearance. Patients with this disorder frequently
seek unnecessary plastic surgery.

Description
Plastic surgery
Plastic surgery includes a number of different
procedures that usually involve skin. Operations to
remove excess fat from the abdomen (‘‘tummy
tucks’’), dermabrasion to remove acne scars or tattoos,
and reshaping the cartilage in children’s ears (otoplasty) are common applications of plastic surgery.
Cosmetic surgery
Most cosmetic surgery is done on the face. It is
intended either to correct disfigurement or to enhance
the patient’s features. The most common cosmetic
2927

Plastic, cosmetic, and reconstructive surgery

Preparation
The Top 10 Elective Cosmetic Surgeries In The U.S. (1999)

Procedure
Liposuction
Breast
augmentation
Eyelid surgery
Face lift
Tummy tuck
Collagen injections
Chemical peel
Laser skin
resurfacing
Rhinoplasty
Forehead lift

Female
Patients

Male
Patients

Total

201,083
167,318

29,782
0

230,865
167,318

120,160
66,096
52,888
48,989
47,359
46,162

21,859
6,697
2,089
4,208
4,215
4,343

142,033
72,793
54,977
53,197
51,589
50,505

34,761
36,995

11,831
3,962

46,596
40,969

procedure for children is correction of a cleft lip or
palate. In adults, the most common procedures are
remodeling of the nose (rhinoplasty), removal of
baggy skin around the eyelids (blepharoplasty), facelifts (rhytidectomy), or changing the size of the breasts
(mammoplasty). Although many people still think of
cosmetic surgery as only for women, growing numbers
of men are choosing to have facelifts and eyelid surgery, as well as hair transplants and ‘‘tummy tucks.’’
Reconstructive surgery

Preparation for nonemergency plastic or reconstructive surgery includes patient education, as well
as medical considerations. Some operations, such as
nose reshaping or the removal of warts, small birthmarks, and tattoos can be done as outpatient procedures under local anesthesia. Most plastic and
reconstructive surgery, however, involves a stay in
the hospital and general anesthesia. Patients are typically asked to stop taking certain prescription medications that affect bleeding for about two weeks before
the procedure and to stop smoking for at least a week
before the operation.
Preparation for reconstructive surgery following
cancer treatment may require much more extensive
counseling and discussion of possible alternatives to
the surgery.
Medical preparation
Preparation for plastic surgery includes the surgeon’s detailed assessment of the parts of the patient’s
body that will be involved. Skin grafts require evaluating suitable areas of the patient’s skin for the right
color and texture to match the skin at the graft site.
Facelifts and cosmetic surgery in the eye area require
very close attention to the texture of the skin and the
placement of surgical cuts (incisions).

Reconstructive surgery is often performed on cancer patients as well as on burn and accident victims. It
may involve the rebuilding of severely fractured bones,
as well as skin grafting. Reconstructive surgery
includes such procedures as the reattachment of an
amputated finger or toe, or implanting a prosthesis.
Prostheses are artificial structures and materials that
are used to replace missing limbs or teeth, or arthritic
hip and knee joints.

Patients scheduled for plastic surgery under general anesthesia will be given a physical examination,
blood and urine tests, and other tests to make sure that
they do not have any previously undetected health
problems or blood clotting disorders. The doctor will
check the list of prescription medications that the
patient may be taking to make sure that none of
them will interfere with normal blood clotting or interact with the anesthetic.

In cancer patients, reconstructive surgery is done
to restore the function as well as the appearance of the
face and other parts of the body. The most commonly
performed reconstructive surgeries of cancer patients
are breast reconstruction, laceration repair, scar revision, and tumor removal.

Patients are asked to avoid using aspirin or medications containing aspirin for a week to two weeks
before surgery, because these drugs lengthen the time
of blood clotting. Smokers are asked to stop smoking
two weeks before surgery because smoking interferes
with the healing process. For some types of plastic
surgery, the patient may be asked to donate several
units of his or her own blood before the procedure, in
case a transfusion is needed during the operation. The
patient will be asked to sign a consent form before the
operation.

The most challenging area of reconstructive surgery involves the structures of the face, neck, and jaw
because trauma or cancer treatments often affect the
patient’s ability to see, eat, taste, swallow, speak, and
hear as well as his or her external appearance. The
surgeon must try to retain as much sensation as possible when performing skin or bone grafts in the head
and neck as well as recreate a reasonably normal
appearance.
2928

Patient education
The doctor will meet with the patient before the
operation is scheduled, in order to explain the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Blepharoplasty—Surgical reshaping of the eyelid.
Dermabrasion—A technique for removing the
upper layers of skin with planing wheels powered
by compressed air.

Aftercare
Medical

Facelift—Plastic surgery performed to remove sagging skin and wrinkles from the patient’s face.
Liposuction—A surgical technique for removing fat
from under the skin by vacuum suctioning.

Medical aftercare following plastic surgery under
general anesthesia includes bringing the patient to a
recovery room, monitoring his or her vital signs, and
giving medications to relieve pain as necessary.
Patients who have had fat removed from the abdomen
may be kept in bed for as long as two weeks. Patients
who have had mammoplasties, breast reconstruction,
and some types of facial surgery typically remain in the
hospital for a week after the operation. Patients who
have had liposuction or eyelid surgery are usually sent
home in a day or two.
Patients who have had outpatient procedures are
usually given antibiotics to prevent infection and are
sent home as soon as their vital signs are normal.
Psychological
Some patients may need follow-up psychotherapy
or counseling after plastic or reconstructive surgery.
These patients typically include children whose
schooling and social relationships have been affected
by birth defects, as well as patients of any age whose
deformities or disfigurements were caused by trauma
from accidents, war injuries, or violent crime.

Risks
The risks associated with plastic, cosmetic, and
reconstructive surgery include the postoperative complications that can occur with any surgical operation
under anesthesia. These complications include wound
infection, internal bleeding, pneumonia, and reactions
to the anesthesia.

Mammoplasty—Surgery performed to change the
size of breasts.
Rhinoplasty—Surgery performed to change the
shape of the nose.



loss of normal feeling or function in the area of the
operation (for example, it is not unusual for women
who have had mammoplasties to lose sensation in
their nipples)



complications resulting from unforeseen technological problems (the best-known example of this problem was the discovery in the mid-1990s that breast
implants made with silicone gel could leak into the
patient’s body).

Normal results
Normal results include the patient’s recovery from
the surgery with satisfactory results and without
complications.
Resources
PERIODICALS



formation of undesirable scar tissue



persistent pain, redness, or swelling in the area of the
surgery



infection inside the body related to inserting a prosthesis. These infections can result from contamination at the time of surgery or from bacteria migrating
into the area around the prosthesis at a later time



anemia or fat embolisms from liposuction



rejection of skin grafts or tissue transplants

Cordeiro, P. G., A. L. Pusic, J. J. Disa, et al. ‘‘Irradiation
after Immediate Tissue Expander/Implant Breast
Reconstruction: Outcomes, Complications, Aesthetic
Results, and Satisfaction among 156 Patients.’’ Plastic
and Reconstructive Surgery 113 (March 2004): 877–881.
Dupin, C., S. Metzinger, and R. Rizzuto. ‘‘Lip
Reconstruction after Ablation for Skin Malignancies.’’
Clinics in Plastic Surgery 31 (January 2004): 69–85.
Guerra, A. B., S. E. Metzinger, R. S. Bidros, et al. ‘‘Bilateral
Breast Reconstruction with the Deep Inferior
Epigastric Perforator (DIEP) Flap: An Experience with
280 Flaps.’’ Annals of Plastic Surgery 52 (March 2004):
246–252.
Hofstra, E. I., S. O. Hofer, J. M. Nauta et al. ‘‘Oral
Functional Outcome after Intraoral Reconstruction
with Nasolabial Flaps.’’ British Journal of Plastic
Surgery 57 (March 2004): 150–155.

GALE ENCYCLOPEDIA OF MEDICINE

2929

In addition to these general risks, plastic, cosmetic, and reconstructive surgery carry specific risks:

Plastic, cosmetic, and reconstructive surgery

procedure and to be sure that the patient is realistic
about the expected results. This consideration is particularly important if the patient is having cosmetic
surgery.

Platelet aggregation test

Losken, A., G. W. Carlson, M. B. Schoemann, et al.
‘‘Factors That Influence the Completion of Breast
Reconstruction.’’ Annals of Plastic Surgery 52 (March
2004): 258–261.
Patrick, C. W. ‘‘Breast Tissue Engineering.’’ Annual Review
of Biomedical Engineering 6 (2004): 109–130.
ORGANIZATIONS

American Academy of Facial Plastic and Reconstructive
Surgery (AAFPRS). 310 South Henry Street,
Alexandria, VA 22314. (703) 299-9291. <http://
www.facemd.org>.
American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://www.amaassn.org>.
American Society of Plastic Surgeons (ASPS). 444 East
Algonquin Road, Arlington Heights, IL 60005. (847)
228-9900. <www.plasticsurgery.org>.

Rebecca J. Frey, PhD

Platelet aggregation test
Definition
Platelets are disk-shaped blood cells that are also
called thrombocytes. They play a major role in the
blood-clotting process. The platelet aggregation test
is a measure of platelet function.

Purpose
The platelet aggregation test aids in the evaluation
of bleeding disorders by measuring the rate and degree
to which platelets form a clump (aggregate) after the
addition of a chemical that stimulates clumping
(aggregation).

involves small cells in the bloodstream called platelets,
which are produced in the bone marrow. Platelets
gather at the site of an injury and clump together to
form a plug, or aggregate, that helps to limit the loss of
blood and promote healing.
Inherited bleeding disorders (e.g., hemophilia or
von Willebrand’s disease) and acquired bleeding problems that occur because of another disorder or a
medication can affect the number of platelets and
their level of function. When these problems are present, the result is a drop in platelet aggregation and a
lengthened bleeding time.
The platelet aggregation test uses a machine called
an aggregometer to measure the cloudiness (turbidity)
of blood plasma. Several different substances called
agonists are used in the test. These agonists include
adenosine diphosphate, epinephrine, thrombin, collagen, and ristocetin. The addition of an agonist to a
plasma sample causes the platelets to clump together,
making the fluid more transparent. The aggregometer
then measures the increased light transmission
through the specimen.

Preparation
The test requires a blood sample. The patient
should either avoid food and drink altogether for
eight hours before the test, or eat only nonfat foods.
High levels of fatty substances in the blood can affect
test results.
Because the use of aspirin and/or aspirin compounds can directly affect test results, the patient
should avoid these medications for two weeks before
the test. If the patient must take aspirin and the test
cannot be postponed, the laboratory should be notified
and asked to verify the presence of aspirin in the blood
plasma. If the results are abnormal, aspirin use must be
discontinued and the test repeated in two weeks.

Precautions
There are many medications that can affect the
results of the platelet aggregation test. The patient
should discontinue as many as possible beforehand.
Some of the drugs that can decrease platelet aggregation include aspirin, some antibiotics, beta blockers,
dextran (Macrodex), alcohol, heparin (Lipo-Hepin),
nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, and warfarin (Coumadin).

Description
There are many factors involved in blood clotting
(coagulation). One of the first steps in the process
2930

Aftercare
Because the platelet aggregation test is ordered
when some type of bleeding problem is suspected, the
patient should be cautioned to watch the puncture site
for signs of additional bleeding.

Risks
Risks for this test are minimal in normal individuals. Patients with bleeding disorders, however, may
have prolonged bleeding from the puncture wound or
the formation of a bruise (hematoma) under the skin
where the blood was withdrawn.
GALE ENCYCLOPEDIA OF MEDICINE

Platelet count

Aggregation—The blood cell clumping process
that is measured in the platelet aggregation test.
Agonist—A chemical that is added to the blood
sample in the platelet aggregation test to stimulate
the clumping process.
Hemophilia—An inherited bleeding disorder
caused by a deficiency of factor VIII, one of a series
of blood proteins essential for blood clotting.
Platelets—Small, round, disk-shaped blood cells
that are involved in clot formation. The platelet
aggregation test measures the clumping ability of
platelets.
Turbidity—The cloudiness or lack of transparency
of a solution.
von Willebrand’s disease—An inherited lifelong
bleeding disorder caused by an abnormal gene,
similar to hemophilia. The gene defect results in a
decreased blood concentration of a substance
called von Willebrand’s factor (vWF).

Definition
A platelet count is a diagnostic test that determines the number of platelets in the patient’s blood.
Platelets, which are also called thrombocytes, are
small disk-shaped blood cells produced in the bone
marrow and involved in the process of blood clotting.
There are normally between 150,000-450,000 platelets
in each microliter of blood. Low platelet counts or
abnormally shaped platelets are associated with bleeding disorders. High platelet counts sometimes indicate
disorders of the bone marrow.

Purpose
The primary functions of a platelet count are to
assist in the diagnosis of bleeding disorders and to
monitor patients who are being treated for any disease
involving bone marrow failure. Patients who have
leukemia, polycythemia vera, or aplastic anemia are
given periodic platelet count tests to monitor their
health.

Description
Normal results

Blood collection and storage

The normal time for platelet aggregation varies
somewhat depending on the laboratory, the temperature, the shape of the vial in which the test is performed, and the patient’s response to different
agonists. For example, the difference between the
response to ristocetin and other products should be
noted because ristocetin triggers aggregation through
a different mechanism than other agonists.

Abnormal results
Prolonged platelet aggregation time can be found
in such congenital disorders as hemophilia and von
Willebrand’s disease, as well as in some connective
tissue disorders. Prolonged aggregation times can
also occur in leukemia or myeloma; after recent
heart/lung bypass or kidney dialysis; and after taking
certain drugs.

Platelet counts use a freshly-collected blood specimen to which a chemical called EDTA has been added
to prevent clotting before the test begins. About 5 mL
of blood are drawn from a vein in the patient’s inner
elbow region. Blood drawn from a vein helps to produce a more accurate count than blood drawn from a
fingertip. Collection of the sample takes only a few
minutes.
After collection, the mean platelet volume of
EDTA-blood will increase over time. This increase is
caused by a change in the shape of the platelets after
removal from the body. The changing volume is relatively stable for a period of one to three hours after
collection. This period is the best time to count the
sample when using electronic instruments, because the
platelets will be within a standard size range.
Counting methods

Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnosticand
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores
GALE ENCYCLOPEDIA OF MEDICINE

Platelets can be observed in a direct blood smear
for approximate quantity and shape. A direct smear is
made by placing a drop of blood onto a microscope
slide and spreading it into a thin layer. After staining
to make the various blood cells easier to see and distinguish, a laboratory technician views the smear
2931

Platelet count

KEY TERMS

Platelet count

through a light microscope. Accurate assessment of
the number of platelets requires other methods of
counting. There are three methods used to count platelets; hemacytometer, voltage-pulse counting, and
electro-optical counting.
HEMACYTOMETER COUNTING. The microscopic
method uses a phase contrast microscope to view
blood on a hemacytometer slide. A sample of the
diluted blood mixture is placed in a hemacytometer,
which is an instrument with a grid etched into its surface
to guide the counting. For a proper count, the platelets
should be evenly distributed in the hemacytometer.
Counts made from samples with platelet clumping are
considered unreliable. Clumping can be caused by several factors, such as clotting before addition of the
anticoagulant and allowing the blood to remain in
contact with a capillary blood vessel during collection.
Errors in platelet counting are more common when
blood is collected from capillaries than from veins.
ELECTRONIC COUNTING. Electronic counting of
platelets is the most common method. There are two
types of electronic counting, voltage-pulse and electrooptical counting systems. In both systems, the collected blood is diluted and counted by passing the
blood through an electronic counter. The instruments
are set to count only particles within the proper size
range for platelets. The upper and lower levels of the
size range are called size exclusion limits. Any cells or
material larger or smaller than the size exclusion limits
will not be counted. Any object in the proper size
range is counted, however, even if it isn’t a platelet.
For these instruments to work properly, the sample
must not contain other material that might mistakenly
be counted as platelets. Electronic counting instruments sometimes produce artificially low platelet
counts. If a platelet and another blood cell pass
through the counter at the same time, the instrument
will not count the larger cell because of the size exclusion limits, which will cause the instrument to accidentally miss the platelet. Clumps of platelets will not be
counted because clumps exceed the upper size exclusion limit for platelets. In addition, if the patient has a
high white blood cell count, electronic counting may
yield an unusually low platelet count because white
blood cells may filter out some of the platelets before
the sample is counted. On the other hand, if the red
blood cells in the sample have burst, their fragments
will be falsely counted as platelets.

Aftercare
Because platelet counts are sometimes ordered to
diagnose or monitor bleeding disorders, patients with
2932

KEY TERMS
Capillaries—The smallest of the blood vessels that
bring oxygenated blood to tissues.
EDTA—A colorless compound used to keep blood
samples from clotting before tests are run. Its chemical name is ethylene-diamine-tetra-acetic acid.
Hemocytometer—An instrument used to count
platelets or other blood cells.
Phase contrast microscope—A light microscope in
which light is focused on the sample at an angle to
produce a clearer image.
Thrombocyte—Another name for platelet.
Thrombocytopenia—An abnormally low platelet
count.
Thrombocytosis—An abnormally high platelet
count. It occurs in polycythemia vera and other
disorders in which the bone marrow produces too
many platelets.

these disorders should be cautioned to watch the puncture site for signs of additional bleeding.

Risks
Risks for a platelet count test are minimal in
normal individuals. Patients with bleeding disorders,
however, may have prolonged bleeding from the puncture wound or the formation of a bruise (hematoma)
under the skin where the blood was withdrawn.

Normal results
The normal range for a platelet count is 150,000450,000 platelets per microliter of blood.

Abnormal results
An abnormally low platelet level (thrombocytopenia) is a condition that may result from increased
destruction of platelets, decreased production, or
increased usage of platelets. In idiopathic thrombocytopenic purpura (ITP), platelets are destroyed at
abnormally high rates. Hypersplenism is characterized
by the collection (sequestration) of platelets in the
spleen. Disseminated intravascular coagulation
(DIC) is a condition in which blood clots occur within
blood vessels in a number of tissues. All of these diseases produce reduced platelet counts.
GALE ENCYCLOPEDIA OF MEDICINE

Resources

include errors in the production of the platelets themselves or errors in the formation, storage, or release of
their chemical signals. These defects can prevent platelets from responding to injuries or from prompting the
action of other factors involved in clot formation.

Causes and symptoms

BOOKS

Berktow, Robert, et al., editors. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

John T. Lohr, PhD

Platelet function disorders can be inherited, but
they may also occur as a symptom of acquired diseases
or as a side effect of certain drugs, including aspirin.
Common symptoms of platelet function disorders
include bleeding from the nose, mouth, vagina, or
anus; pinpoint bruises and purplish patches on the
skin; and abnormally heavy menstrual bleeding.

Diagnosis

Platelet function disorders
Definition
Platelets are elements within the bloodstream that
recognize and cling to damaged areas inside blood
vessels. When they do this, the platelets trigger a series
of chemical changes that result in the formation of a
blood clot. There are certain hereditary disorders that
affect platelet function and impair their ability to start
the process of blood clot formation. One result is the
possibility of excessive bleeding from minor injuries or
menstrual flow.

Description
Platelets are formed in the bone marrow–a spongy
tissue located inside the long bones of the body–as
fragments of a large precursor cell (a megakaryocyte).
These fragments circulate in the bloodstream and
form the first line of defense against blood escaping
from injured blood vessels.
Damaged blood vessels release a chemical signal
that increases the stickiness of platelets in the area of
the injury. The sticky platelets adhere to the damaged
area and gradually form a platelet plug. At the same
time, the platelets release a series of chemical signals
that prompt other factors in the blood to reinforce the
platelet plug. Between the platelet and its reinforcements, a sturdy clot is created that acts as a patch while
the damaged area heals.
There are several hereditary disorders characterized by some impairment of the platelet’s action.
Examples include von Willebrand’s disease,
Glanzmann’s thrombasthenia, and Wiskott-Aldrich
syndrome. Vulnerable aspects of platelet function
GALE ENCYCLOPEDIA OF MEDICINE

In diagnosing platelet function disorders, specific
tests are needed to determine whether the problem is
caused by low numbers of platelets or impaired platelet function. A blood platelet count and bleeding time
are common screening tests. If these tests confirm that
the symptoms are due to impaired platelet function,
further tests are done–such as platelet aggregation or
an analysis of the platelet proteins–that pinpoint the
exact nature of the defect.

Treatment
Treatment is intended to prevent bleeding and stop
it quickly when it occurs. For example, patients are
advised to be careful when they brush their teeth to
reduce damage to the gums. They are also warned
against taking medications that interfere with platelet
function. Some patients may require iron and folate
supplements to counteract potential anemia. Platelet
transfusions may be necessary to prevent life-threatening hemorrhaging in some cases. Bone marrow transplantation can cure certain disorders but also carries
some serious risks. Hormone therapy is useful in treating heavy menstrual bleeding. Von Willebrand’s disease
can be treated with desmopressin (DDAVP, Stimate).

Prognosis
The outcome depends on the specific disorder and
the severity of its symptoms. Platelet function disorders range from life-threatening conditions to easily
treated or little-noticed problems.

Prevention
Inherited platelet function disorders cannot be
prevented except by genetic counseling; however,
2933

Platelet function disorders

Abnormally high platelet levels (thrombocytosis)
may indicate either a benign reaction to an infection,
surgery, or certain medications; or a disease like polycythemia vera, in which the bone marrow produces
too many platelets too quickly.

Pleural biopsy

ordered when a chest x ray indicates a pleural-based
tumor, reaction, or thickening of the lining.

KEY TERMS
Anemia—A condition in which inadequate quantities of hemoglobin and red blood cells are
produced.
Bone marrow—A spongy tissue located within the
body’s flat bones–including the hip and breast
bones and the skull. Marrow contains stem cells,
the precursors to platelets and red and white blood
cells.
Hemoglobin—The substance inside red blood cells
that enables them to carry oxygen.
Megakaryocyte—A large bone marrow cell with a
lobed nucleus that is the precursor cell of blood
platelets.
Platelets—Fragments of a large precursor cell (a
megakaryocyte) found in the bone marrow. These
fragments adhere to areas of blood vessel damage
and release chemical signals that direct the formation of a blood clot.

some acquired function disorders may be guarded
against by avoiding substances that trigger the
disorder.
Resources
PERIODICALS

Liesner, R. J., and S. J. Machin. ‘‘Platelet Disorders.’’British
Medical Journal 314, no. 7083 (1997): 809.

Julia Barrett

Precautions
Because pleural biopsy is an invasive procedure, it
is not recommended for patients with severe bleeding
disorders.

Description
Pleural biopsy is usually ordered when pleural
fluid obtained by another procedure called thoracentesis (aspiration of pleural fluid) suggests infection,
signs of cancer, or tuberculosis. Pleural biopsies are
85–90% accurate in diagnosing these diseases.
The procedure most often performed for pleural
biopsy is called a percutaneous (passage through the
skin by needle puncture) needle biopsy. The procedure
takes 30–45 minutes, although the biopsy needle itself
remains in the pleura for less than one minute. This
type of biopsy is usually performed by a physician at
bedside, if the patient is hospitalized, or in the doctor’s
office under local anesthetic.
The actual procedure begins with the patient in a
sitting position, shoulders and arms elevated and supported. The skin overlying the biopsy site is anesthetized and a small incision is made to allow insertion of
the biopsy needle. This needle is inserted with a cannula (a plastic or metal tube) until fluid is removed.
Then the inner needle is removed and a trocar (an
instrument for withdrawing fluid from a cavity) is
inserted to obtain the actual biopsy specimen. As
many as three separate specimens are taken from different sites during the procedure. These specimens are
then placed into a fixative solution and sent to the
laboratory for tissue (histologic) examination.

Preparation

Pleural biopsy
Definition
The pleura is the membrane that lines the lungs
and chest cavity. A pleural biopsy is the removal of
pleural tissue for examination.

Purpose
Pleural biopsy is done to differentiate between
benign and malignant disease, to diagnose viral, fungal, or parasitic diseases, and to identify a condition
called collagen vascular disease of the pleura. It is also
2934

Preparations for this procedure vary, depending
on the type of procedure requested. Pleural biopsy can
be performed in several ways: percutaneous needle
biopsy (described above), by thoracoscopy (insertion
of a visual device called a laparoscope into the pleural
space for inspection), or by open pleural biopsy, which
requires general anesthesia.

Aftercare
Potential complications of this procedure include
bleeding or injury to the lung, or a condition called
pneumothorax, in which air enters the pleural cavity
(the space between the two layers of pleura lining the
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Risks for this procedure include respiratory distress on the side of the biopsy, as well as bleeding,
possible shoulder pain, pneumothorax (immediate)
or pneumonia (delayed).

Normal results
Normal findings indicate no evidence of any
pathologic or disease conditions.

Abnormal results
Abnormal findings include tumors called neoplasms (any new or abnormal growth) that can be
either benign or malignant. Pleural tumors are divided
into two classifications: primary (mesothelioma), or
metastatic (arising from cancer sites elsewhere in the
body). These tumors are often associated with an
accumulation of fluid between the pleural layers called
a pleural effusion, which itself may be caused by pneumonia, heart failure, cancer, or blood clot in the lungs
(pulmonary embolism).
Other causes of abnormal findings include viral,
fungal, or parasitic infections, and tuberculosis.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Description
There are two thin membranes in the chest, one
(the visceral pleura) lining the lungs, and the other (the
parietal pleura) covering the inside of the chest wall.
Normally, small blood vessels in the pleural linings
produce a small amount of fluid that lubricates the
opposed pleural membranes so that they can glide
smoothly against one another during breathing movements. Any extra fluid is taken up by blood and lymph
vessels, maintaining a balance. When either too much
fluid forms or something prevents its removal, the
result is an excess of pleural fluid–an effusion. The
most common causes are disease of the heart or
lungs, and inflammation or infection of the pleura.
Pleural effusion itself is not a disease as much as a
result of many different diseases. For this reason, there
is no ‘‘typical’’ patient in terms of age, sex, or other
characteristics. Instead, anyone who develops one of
the many conditions that can produce an effusion may
be affected.
There are two types of pleural effusion: the transudate and the exudate. This is a very important point
because the two types of fluid are very different, and
which type is present points to what sort of disease is
likely to have produced the effusion. It also can suggest the best approach to treatment.
Transudates
A transudate is a clear fluid, similar to blood
serum, that forms not because the pleural surfaces
themselves are diseased, but because the forces that
normally produce and remove pleural fluid at the same
rate are out of balance. When the heart fails, pressure
in the small blood vessels that remove pleural fluid is
increased and fluid ‘‘backs up’’ in the pleural space,
forming an effusion. Or, if too little protein is present
in the blood, the vessels are less able to hold the fluid
part of blood within them and it leaks out into the
pleural space. This can result from disease of the liver
or kidneys, or from malnutrition.
Exudates

Pleural effusion
Definition
Pleural effusion occurs when too much fluid collects in the pleural space (the space between the two
layers of the pleura). It is commonly known as ‘‘water
on the lungs.’’ It is characterized by shortness of
breath, chest pain, gastric discomfort (dyspepsia), and
cough.
GALE ENCYCLOPEDIA OF MEDICINE

An exudate–which often is a cloudy fluid, containing cells and much protein–results from disease of the
pleura itself. The causes are many and varied. Among
the most common are infections such as bacterial
pneumonia and tuberculosis; blood clots in the lungs;
and connective tissue diseases, such as rheumatoid
arthritis. Cancer and disease in organs such as the
pancreas also may give rise to an exudative pleural
effusion.
2935

Pleural effusion

lungs and the chest wall). Because of these possibilities, the patient is to report any shortness of breath,
and to note any signs of bleeding, decreased blood
pressure, or increased pulse rate.

Pleural effusion

Special types of pleural effusion
Some of the pleural disorders that produce an
exudate also cause bleeding into the pleural space. If
the effusion contains half or more of the number of red
blood cells present in the blood itself, it is called
hemothorax. When a pleural effusion has a milky
appearance and contains a large amount of fat, it is
called chylothorax. Lymph fluid that drains from tissues throughout the body into small lymph vessels
finally collects in a large duct (the thoracic duct) running through the chest to empty into a major vein.
When this fluid, or chyle, leaks out of the duct into the
pleural space, chylothorax is the result. Cancer in the
chest is a common cause.

Causes and symptoms
Causes of transudative pleural effusion
Among the most important specific causes of a
transudative pleural effusion are:


Congestive heart failure. This causes pleural effusions in about 40% of patients and is often present
on both sides of the chest. Heart failure is the most
common cause of bilateral (two-sided) effusion.
When only one side is affected it usually is the right
(because patients usually lie on their right side).



Pericarditis. This is an inflammation of the pericardium, the membrane covering the heart.



Too much fluid in the body tissues, which spills over
into the pleural space. This is seen in some forms of
kidney disease; when patients have bowel disease and
absorb too little of what they eat; and when an
excessive amount of fluid is given intravenously.



Liver disease. About 5% of patients with a chronic
scarring disease of the liver called cirrhosis develop
pleural effusion.



Patients with any of a wide range of infections by a
virus, fungus, or parasite that involve the lungs may
have pleural effusion.



Up to half of all patients who develop blood clots in
their lungs (pulmonary embolism) will have pleural
effusion, and this sometimes is the only sign of
embolism.



Connective tissue diseases, including rheumatoid
arthritis, lupus, and Sjögren’s syndrome may be complicated by pleural effusion.



Patients with disease of the liver or pancreas may
have an exudative effusion, and the same is true for
any patient who undergoes extensive abdominal surgery. About 30% of patients who undergo heart
surgery will develop an effusion.



Injury to the chest may produce pleural effusion in
the form of either hemothorax or chylothorax.
Symptoms

The key symptom of a pleural effusion is shortness
of breath. Fluid filling the pleural space makes it hard
for the lungs to fully expand, causing the patient to
take many breaths so as to get enough oxygen. When
the parietal pleura is irritated, the patient may have
mild pain that quickly passes or, sometimes, a sharp,
stabbing pleuritic type of pain. Some patients will have
a dry cough. Occasionally a patient will have no symptoms at all. This is more likely when the effusion
results from recent abdominal surgery, cancer, or
tuberculosis. Tapping on the chest will show that the
usual crisp sounds have become dull, and on listening
with a stethoscope the normal breath sounds are
muted. If the pleura is inflamed, there may be a scratchy sound called a ‘‘pleural friction rub.’’

Diagnosis



Pleural tumors account for up to 40% of one-sided
pleural effusions. They may arise in the pleura itself
(mesothelioma), or from other sites, notably the lung.



Tuberculosis in the lungs may produce a long-lasting
exudative pleural effusion.

When pleural effusion is suspected, the best way
to confirm it is to take chest x rays, both straight-on
and from the side. The fluid itself can be seen at the
bottom of the lung or lungs, hiding the normal lung
structure. If heart failure is present, the x-ray shadow
of the heart will be enlarged. An ultrasound scan may
disclose a small effusion that caused no abnormal
findings during chest examination. A computed tomography scan is very helpful if the lungs themselves are
diseased.



Pneumonia affects about three million persons each
year, and four of every ten patients will develop
pleural effusion. If effective treatment is not provided, an extensive effusion can form that is very
difficult to treat.

In order to learn what has caused the effusion, a
needle or catheter is often used to obtain a fluid sample, which is examined for cells and its chemical makeup. This procedure, called a thoracentesis, is the way
to determine whether an effusion is a transudate or

Causes of exudative pleural effusions
A wide range of conditions may be the cause of an
exudative pleural effusion:

2936

GALE ENCYCLOPEDIA OF MEDICINE

Treatment
The best way to clear up a pleural effusion is to
direct treatment at what is causing it, rather than
treating the effusion itself. If heart failure is reversed
or a lung infection is cured by antibiotics, the effusion
will usually resolve. However, if the cause is not
known, even after extensive tests, or no effective treatment is at hand, the fluid can be drained away by
placing a large-bore needle or catheter into the pleural
space, just as in diagnostic thoracentesis. If necessary,
this can be repeated as often as is needed to control the
amount of fluid in the pleural space. If large effusions
continue to recur, a drug or material that irritates the
pleural membranes can be injected to deliberately
inflame them and cause them to adhere close
together–a process called sclerosis. This will prevent
further effusion by eliminating the pleural space. In
the most severe cases, open surgery with removal of a
rib may be necessary to drain all the fluid and close the
pleural space.

Prognosis
When the cause of pleural effusion can be determined and effectively treated, the effusion itself will
reliably clear up and should not recur. In many other
cases, sclerosis will prevent sizable effusions from
recurring. Whenever a large effusion causes a patient
to be short of breath, thoracentesis will make breathing easier, and it may be repeated if necessary. To a
great extent, the outlook for patients with pleural
effusion depends on the primary cause of effusion
and whether it can be eliminated. Some forms of
pleural effusion, such as that seen after abdominal
surgery, are only temporary and will clear without
specific treatment. If heart failure can be controlled,
the patient will remain free of pleural effusion. If, on
the other hand, effusion is caused by cancer that cannot be controlled, other effects of the disease probably
will become more important.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Culture—A test that exposes a sample of body fluid
or tissue to special material to see whether bacteria
or another type of microorganism is present.
Dyspepsia—A vague feeling of being too full and
having heartburn, bloating, and nausea. Usually
felt after eating.
Exudate—The type of pleural effusion that results
from inflammation or other disease of the pleura
itself. It features cloudy fluid containing cells and
proteins.
Pleura or pleurae—A delicate membrane that
encloses the lungs. The pleura is divided into two
areas separated by fluid–the visceral pleura, which
covers the lungs, and the parietal pleura, which
lines the chest wall and covers the diaphragm.
Pleural cavity—The area of the thorax that contains
the lungs.
Pleural space—The potential area between the
visceral and parietal layers of the pleurae.
Pneumonia—An acute inflammation of the lungs,
usually caused by bacterial infection.
Sclerosis—The process by which an irritating material is placed in the pleural space in order to inflame
the pleural membranes and cause them to stick
together, eliminating the pleural space and recurrent effusions.
Thoracentesis—Placing a needle, tube, or catheter
in the pleural space to remove the fluid of pleural
effusion. Used for both diagnosis and treatment.
Transudate—The type of pleural effusion seen with
heart failure or other disorders of the circulation. It
features clear fluid containing few cells and little
protein.

Prevention
Because pleural effusion is a secondary effect of
many different conditions, the key to preventing it is to
promptly diagnose the primary disease and provide
effective treatment. Timely treatment of infections
such as tuberculosis and pneumonia will prevent
many effusions. When effusion occurs as a drug sideeffect, withdrawing the drug or using a different one
may solve the problem. On rare occasions, an effusion
occurs because fluid meant for a vein is mistakenly
injected into the pleural space. This can be prevented
by making sure that proper technique is used.
2937

Pleural effusion

exudate, giving a clue as to the underlying cause. In
some cases–for instance when cancer or bacterial
infection is present–the specific cause can be determined and the correct treatment planned. Culturing
a fluid sample can identify the bacteria that cause
tuberculosis or other forms of pleural infection. The
next diagnostic step is to take a tissue sample, or
pleural biopsy, and examine it under a microscope. If
the effusion is caused by lung disease, placing a viewing tube (bronchoscope) through the large air passages
will allow the examiner to see the abnormal appearance of the lungs.

Pleurisy

Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

David A. Cramer, MD

Pleural fluid analysis see Thoracentesis

also causes a chest noise that ranges from a faint
squeak to a loud creak. This characteristic sound is
called a ‘‘friction rub.’’
Pleurisy cases are classified either as having
pleural effusion or as being ‘‘dry.’’ Pleural effusion is
more common and refers to an accumulation of fluid
within the pleural space; dry pleurisy is inflammation
without fluid build-up. Less pain occurs with pleural
effusion because the fluid forces the membrane surfaces apart. However, pleural effusion causes additional complications because it places pressure on the
lungs. This leads to respiratory distress and possible
lung collapse.

Causes and symptoms

Pleurisy
Definition
Pleurisy is an inflammation of the membrane that
surrounds and protects the lungs (the pleura).
Inflammation occurs when an infection or damaging
agent irritates the pleural surface. As a consequence,
sharp chest pains are the primary symptom of
pleurisy.

Description
Pleurisy, also called pleuritis, is a condition that
generally stems from an existing respiratory infection,
disease, or injury. In people who have otherwise good
health, respiratory infections or pneumonia are the
main causes of pleurisy. This condition used to be
more common, but with the advent of antibiotics and
modern disease therapies, pleurisy has become less
prevalent.
The pleura is a double-layered structure made up
of an inner membrane, which surrounds the lungs, and
an outer membrane, which lines the chest cavity. The
pleural membranes are very thin, close together, and
have a fluid coating in the narrow space between them.
This liquid acts as a lubricant, so that when the lungs
inflate and deflate during breathing, the pleural surfaces can easily glide over one another.
Pleurisy occurs when the pleural surfaces rub
against one another, due to irritation and inflammation. Infection within the pleural space is the most
common irritant, although the abnormal presence of
air, blood, or cells can also initiate pleurisy.These disturbances all act to displace the normal pleural fluid,
which forces the membranes to rub, rather than glide,
against one another. This rubbing irritates nerve endings in the outer membrane and causes pain. Pleurisy
2938

A variety of conditions can give rise to pleurisy.
The following list represents the most common
sources of pleural inflammation.


infections, including pneumonia, tuberculosis, and
other bacterial or viral respiratory infections



immune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and sarcoidosis



diseases, including cancer, pancreatitis, liver cirrhosis, and heart or kidney failure



injury, from a rib fracture, collapsed lung, esophagus
rupture, blood clot, or material such as asbestos



drug reactions, from certain drugs used to treat
tuberculosis (isoniazid), cancer (methotrexate, procarbazine), or the immune disorders mentioned
above (hydralazine, procainamide, phenytoin,
quinidine)
Symptomatic pain

The hallmark symptom of pleurisy is sudden,
intense chest pain that is usually located over the
area of inflammation. Although the pain can be constant, it is usually most severe when the lungs move
during breathing, coughing, sneezing, or even talking.
The pain is usually described as shooting or stabbing,
but in minor cases it resembles a mild cramp. When
pleurisy occurs in certain locations, such as near the
diaphragm, the pain may be felt in other areas such as
the neck, shoulder, or abdomen (referred pain).
Another indication of pleurisy is that holding one’s
breath or exerting pressure against the chest causes
pain relief.
Breathing difficulties
Pleurisy is also characterized by certain respiratory symptoms. In response to the pain, pleurisy
GALE ENCYCLOPEDIA OF MEDICINE

Additional symptoms of pleurisy are specific to
the illness that triggers the condition. Thus, if infection
is the cause, then chills, fever, and fatigue will be likely
pleurisy symptoms.

Diagnosis
The distinctive pain of pleurisy is normally the
first clue physicians use for diagnosis. Doctors usually
feel the chest to find the most painful area, which is the
likely site of inflammation. A stethoscope is also used
to listen for abnormal chest sounds as the patient
breathes. If the doctor hears the characteristic friction
rub, the diagnosis of pleurisy can be confirmed.
Sometimes, a friction rub is masked by the presence
of pleural effusion and further examination is needed
for an accurate diagnosis.
Identifying the actual illness that causes pleurisy is
more difficult. To make this diagnosis, doctors must
evaluate the patient’s history, additional symptoms,
and laboratory test results. A chest x ray may also be
taken to look for signs of accumulated fluid and other
abnormalities. Possible causes, such as pneumonia,
fractured ribs, esophagus rupture, and lung tumors
may be detected on an x ray. Computed tomography
scan (CT scan) and ultrasound scans are more powerful diagnostic tools used to visualize the chest cavity.
Images from these techniques more clearly pinpoint
the location of excess fluid or other suspected
problems.
The most helpful information in diagnosing the
cause of pleurisy is a fluid analysis. Once the doctor
knows the precise location of fluid accumulation, a
sample is removed using a procedure called thoracentesis. In this technique, a fine needle is inserted into the
chest to reach the pleural space and extract fluid. The
fluid’s appearance and composition is thoroughly
examined to help doctors understand how the fluid
was produced. Several laboratory tests are performed
to analyze the chemical components of the fluid. These
tests also determine whether infection-causing bacteria or viruses are present. In addition, cells within
the fluid are identified and counted. Cancerous cells
can also be detected to learn whether the pleurisy is
caused by a malignancy.
In certain instances, such as dry pleurisy, or when
a fluid analysis is not informative, a biopsy of the
GALE ENCYCLOPEDIA OF MEDICINE

pleura may be needed for microscopic analysis. A
sample of pleural tissue can be obtained several
ways: with a biopsy needle, by making a small incision
in the chest wall, or by using a thoracoscope (a videoassisted instrument for viewing the pleural space and
collecting samples).

Treatment
Pain management
The pain of pleurisy is usually treated with analgesic and anti-inflammatory drugs, such as acetaminophen, ibuprofen, and indomethacin. People with
pleurisy may also receive relief from lying on the painful side. Sometimes, a painful cough will be controlled
with codeine-based cough syrups. However, as the
pain eases, a person with pleurisy should try to breathe
deeply and cough to clear any congestion, otherwise
pneumonia may occur. Rest is also important to aid in
the recovery process.
Treating the source
The treatment used to cure pleurisy is ultimately
defined by the underlying cause. Thus, pleurisy from a
bacterial infection can be successfully treated with
antibiotics, while no treatment is given for viral infections that must run their course. Specific therapies
designed for more chronic illnesses can often cause
pleurisy to subside. For example, tuberculosis pleurisy
is treated with standard anti-tuberculosis drugs. With
some illnesses, excess fluid continues to accumulate
and causes severe respiratory distress. In these individuals, the fluid may be removed by thoracentesis, or
the doctor may insert a chest tube to drain large
amounts. If left untreated, a more serious infection
may develop within the fluid, called empyema.

Alternative treatment
Alternative treatments can be used in conjunction
with conventional treatment to help heal pleurisy.
Acupuncture and botanical medicines are alternative
approaches for alleviating pleural pain and breathing
problems. An herbal remedy commonly recommended is pleurisy root (Asclepias tuberosa), so
named because of its use by early American settlers
who learned of this medicinal plant from Native
Americans. Pleurisy root helps to ease pain, inflammation, and breathing difficulties brought on by
pleurisy. This herb is often used in conjunction with
mullein (Verbascum thapsus) or elecampane (Inula
helenium), which serve as expectorants to clear excess
mucus from the lungs. In addition, there are many
2939

Pleurisy

patients commonly have a rapid, shallow breathing
pattern. Pleural effusion can also cause shortness of
breath, as excess fluid makes expanding the lungs difficult. If severe breathing difficulties persist, patients
may experience a blue colored complexion (cyanosis).

Pneumococcal pneumonia

KEY TERMS
Effusion—The accumulation of fluid within a cavity, such as the pleural space.
Empyema—An infection that causes pus to accumulate in the pleural space. The pus may cause a
tear in the pleural membrane, which allows the
infection to spread to other areas in the body.
Intravenous antibiotics are often given to control
the infection.
Inflammation—An accumulation of fluid and cells
within tissue that is often caused by infection and
the immune response that occurs as a result.
Pneumonia—A condition caused by bacterial or
viral infection that is characterized by inflammation of the lungs and fluid within the air passages.
Pneumonia is often an underlying cause of
pleurisy.
Referred pain—The presence of pain in an area
other than where it originates. In some pleurisy
cases, referred pain occurs in the neck, shoulder,
or abdomen.

patients. Generally speaking, the prognosis for
pleurisy is linked to the seriousness of its cause.
Therefore, the outcome of pleurisy caused by a disease
such as cancer will vary depending on the type and
location of the tumor.

Prevention
Preventing pleurisy is often a matter of providing
early medical attention to conditions that can cause
pleural inflammation. Along this line, appropriate
antibiotic treatment of bacterial respiratory infections
may successfully prevent some cases of pleurisy.
Maintaining a healthy lifestyle and avoiding exposure
to harmful substances (for example, asbestos) are
more general preventative measures.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Julie A. Gelderloos
other respiratory herbs that are used as expectorants
or for other actions on the respiratory system. Herbs
thought to combat infection, such as echinacea
(Echinacea spp.) are also included in herbal pleurisy
remedies. Anitviral herbs, such as Lomatium dissectum
and Ligusticum porteri, can be used if the pleurisy is of
viral origin. Traditional Chinese medicine uses the herb
ephedra (Ephedra sinica), which acts to open air passages and alleviate respiratory difficulties in pleurisy
patients. Dietary recommendations include eating
fresh fruits and vegetables, adequate protein, and
good quality fats (omega–3 fatty acids are anti-inflammatory and are found in fish and flax oil). Taking
certain nutritional supplements, especially large
doeses of vitamin C, may also provide health benefits
to people with pleurisy. Contrast hydrotherapy applied
to the chest and back, along with compresses (cloths
soaked in an herbal solution) or poultices (crushed
herbs applied directly to the skin) of respiratory
herbs, can assist in the healing process. Homeopathic
treatment, guided by a trained practitioner, can be
effective in resolving pleurisy.

Prognosis
Prompt diagnosis, followed by appropriate treatment, ensures a good recovery for most pleurisy
2940

Pleuritis see Pleurisy
Plumbism see Lead poisoning
PMS see Premenstrual syndrome

Pneumococcal pneumonia
Definition
Pneumococcal pneumonia is a common but serious infection and inflammation of the lungs. It is
caused by the bacterium Streptococcus pneumoniae.

Description
The
gram-positive,
spherical
bacteria,
Streptococcus pneumoniae, is the cause of many
human diseases, including pneumonia. Although the
bacteria can normally be found in the nose and throat
of healthy individuals, it can grow and cause infection
when the immune system is weakened. Infection
usually begins with the upper respiratory tract and
then travels into the lungs. Pneumonia occurs when
the bacteria find their way deep into the lungs, to the
GALE ENCYCLOPEDIA OF MEDICINE

Those people most at risk of developing pneumococcal pneumonia have a weakened immune system.
This includes the elderly, infants, cancer patients,
AIDS patients, post-operative patients, alcoholics,
and those with diabetes. Pneumococcal pneumonia is
a disease that has a high rate of hospital transmission,
putting hospital patients at greater risk. Prior lung
infections also makes someone more likely to develop
pneumococcal pneumonia. The disease can be most
severe in patients who have had their spleen removed.
It is the spleen that is responsible for removing the
bacteria from the blood. Cases of pneumonia, which is
spread by close contact, seem to occur most often
between November through April. If not treated, the
disease can spread, causing continually decreasing
lung function, heart problems, and arthritis.

Causes and symptoms
Symptoms of bacterial pneumonia include a
cough, sputum (mucus) production that may be puslike or bloody, shaking and chills, fever, and chest
pain. Symptoms often have an abrupt beginning and
occur after an upper respiratory infection such as a
cold. Symptoms may differ somewhat in the elderly,
with minimal cough, no sputum and no fever, but
rather tiredness and confusion leading to hypothermia
and shock.

Diagnosis
The presence of symptoms and a physical exam
that reveals abnormal lung sounds usually suggest the
presence of pneumonia. Diagnosis is typically made
from an x ray of the lungs, which indicates the accumulation of fluid. Additional tests that may be done
include a complete blood count, a sputum sample for
microscopic examination and culture for Streptococcus
pneumoniae, and possibly blood cultures.

Treatment
Depending on the severity of the disease, antibiotics are given either at home or in the hospital.
Historically, the treatment for pneumococcal
GALE ENCYCLOPEDIA OF MEDICINE

pneumonia has been penicillin. An increasing number
of cases of pneumococcal pneumonia have become
partially or completely resistant to penicillin, making
it less effective in treating this disease. Other effective
antibiotics include amoxicillin and erythromycin. If
these antibiotics are not effective, vancomycin or
cephalosporin may alternatively be used.
Symptoms associated with pneumococcal pneumonia can also be treated. For instance, fever can be
treated with aspirin or acetaminophen. Supplemental
oxygen and intravenous fluids may help. Patients are
advised to get plenty of rest and take increased
amounts of fluids. Coughing should be promoted
because it helps to clear the lungs of fluid.

Alternative treatment
Being a serious, sometimes fatal disease, pneumococcal pneumonia is best treated as soon as possible
with antibiotics. However, there are alternative treatments that both support this conventional treatment
and prevent recurrences. Maintaining a healthy
immune system is important. One way to do this is
by taking the herb, echinacea (Echinacea spp.).
Getting plenty of rest and reducing stress can help
the body heal. Some practitioners feel that mucusproducing foods (including dairy products, eggs, gluten-rich grains such as wheat, oats, rye, as well as
sugar) can contribute to the lung congestion that
accompanies pneumonia. Decreasing these foods and
increasing the amount of fresh fruits and vegetables
may help to decrease lung congestion. Adequate protein in the diet is also essential for the body to produce
antibodies. Contrast and constitutional hydrotherapy
can be very helpful in treating cases of pneumonia.
Other alternative therapies, including acupuncture,
Chinese herbal medicine, and homeopathy, can be
very useful during the recovery phase, helping the
body to rebuild after the illness and contributing to
the prevention of recurrences.

Prognosis
Simple, uncomplicated cases of pneumococcal
pneumonia will begin to respond to antibiotics in
48 to72 hours. Full recovery from pneumonia, however, is greatly dependent on the age and overall health
of the individual. Normally, healthy and younger
patients can recover in only a few days, while the
elderly or otherwise weakened individuals may not
recover for several weeks. Complications may develop
which give a poorer prognosis. Even when promptly
and properly diagnosed, such weakened patients may
die of their pneumonia.
2941

Pneumococcal pneumonia

area called the alveoli, or air sacs. This is the functional part of the lungs where oxygen is absorbed into
the blood. Once in the alveoli, Streptococcus pneumoniae begin to grow and multiply. White blood cells and
immune proteins from the blood also accumulate at
the site of infection in the alveoli. As the alveoli fill
with these substances and fluid, they can no longer
function in the exchange of oxygen. This fluid filling of
the lungs is how pneumonia is defined.

Pneumocystis pneumonia

KEY TERMS
Acetaminophen—A drug used for pain relief as
well as to decrease fever. A common trade name
for the drug is Tylenol.
Aspirin—A commonly used drug for pain relief and
to decrease fever.
Bronchi—Two main branches of the trachea that
go into the lungs. This then further divides into the
bronchioles and alveoli.

weighed with the increased likelihood of developing
penicillin-resistant infections.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Cindy L. A. Jones, PhD

Sputum—A substance that comes up from the
throat when coughing or clearing the throat. It is
important since it contains materials from the
lungs.

Pneumocystis pneumonia
Prevention
Vaccination
Recently, a vaccination has become available for
the prevention of pneumococcal pneumonia. This vaccination is generally recommended for people with a
high likelihood of developing pneumococcal infection
or for those in whom a serious complication of infection is likely to develop. This would include persons
over the age of 65, as well as those with:


chronic pulmonary disease



advanced cardiovascular disease



diabetes mellitus



alcoholism



cirrhosis



chronic kidney disease



spleen dysfunction, or removal of spleen



immunosuppression (cancer, organ transplant or
AIDS)



sickle cell anemia

Unfortunately, those people for whom the vaccination is most recommended are also those who are
least likely to respond favorably to a vaccination.
Therefore, the overall effectiveness of this vaccine
remains questionable.
Antibiotics
The use of oral penicillin to prevent infection may
be recommended for some patients at high risk, such
as children with sickle cell disease and those with a
spleen removed. This treatment, however, must be
2942

Definition
Pneumocystis pneumonia is a lung infection that
occurs primarily in people with weakened immune
systems–especially people who are HIV-positive. The
disease agent is an organism whose biological classification is still uncertain. Pneumocystis carinii was
originally thought to be a one-celled organism (a protozoan), but more recent research suggests that it is a
fungus. Although its life cycle is known to have three
stages, its method of reproduction is not yet completely understood. The complete name of the disease is
Pneumocystis carinii pneumonia, often shortened to
PCP. PCP is also sometimes called pneumocystosis.

Description
Pneumonia as a general term refers to a severe
lung inflammation. In pneumocystis pneumonia, this
inflammation is caused by the growth of Pneumocystis
carinii, a fungus-like organism that is widespread in
the environment. PCP is ordinarily a rare disease,
affecting only people with weakened immune systems.
Many of these people are patients receiving drugs for
organ transplants or cancer treatment. With the rising
incidence of AIDS, however, PCP has become primarily associated with AIDS patients. In fact, as many as
75% of AIDS patients have developed PCP. It has also
been the leading cause of death in AIDS patients.
Transmission
The organism that causes PCP is widely distributed in nature and is transmitted through the air. When
the organism is inhaled, it enters the upper respiratory
tract and infects the tiny air sacs at the ends of the
GALE ENCYCLOPEDIA OF MEDICINE

Person-to-person infection does not appear to be
very common; however, clusters of PCP outbreaks in
hospitals and groups of immunocompromised people
indicate that patients with active PCP should not be
exposed to others with weakened immune systems. It
is thought that many people actually acquire mild
Pneumocystis carinii infections from time to time, but
are protected by their immune systems from developing a full-blown case of the disease.

Causes and symptoms
Causes
P. carinii is an opportunistic organism. This
means that it causes disease only under certain conditions, as when a person is immunocompromised.
Under these circumstances, P. carinii can multiply
and cause pneumonia. The mechanisms of the organism’s growth within the alveoli are not fully understood. As the pneumocystis organism continues to
replicate, it gradually fills the alveoli. As the pneumonia becomes more severe, fluid accumulates and tissue
scarring occurs. These changes result in decreased
respiratory function and lower levels of oxygen in the
blood.
High-risk groups
Some patients are at greater risk of developing
PCP. These high-risk groups include:


premature infants



patients with immunodeficiency diseases, including
severe combined immunodeficiency disease (SCID)
and acquired immunodeficiency syndrome (AIDS),



patients receiving immunosuppressive drugs, especially cortisone-like drugs (corticosteroids)



Patients with protein malnutrition.

AIDS is currently the most common risk factor
for PCP in the United States. PCP is, however, also
found in countries with widespread hunger and poor
hygiene.
Symptoms
The incubation period of PCP is not definitely
known, but is thought to be between four and eight
GALE ENCYCLOPEDIA OF MEDICINE

weeks. The major symptoms include shortness of
breath, fever, and a nonproductive cough. Less common symptoms include production of sputum, blood
in the sputum, difficulty breathing, and chest pain.
Most patients will have symptoms for one to two
weeks before seeing a physician. Occasionally, the
disease will spread outside of the lung to other organs,
including the lymph nodes, spleen, liver, or bone
marrow.

Diagnosis
The diagnosis of PCP begins with a thorough
physical examination and blood tests. Although imaging studies are helpful in identifying abnormal areas
in the lungs, the diagnosis of PCP must be confirmed
by microscopic identification of the organism in the
lung. Samples may be taken from the patient’s sputum, or may be obtained via bronchoscopy or lung
biopsy. Because of the severity of the disease, many
physicians will proceed to treat patients with symptoms of pneumocystis pneumonia if they belong to a
high-risk group, without the formality of an actual
diagnosis. The severity of PCP can be measured by
x-ray studies and by determining the amount of
oxygen and carbon dioxide present in the patient’s
blood.

Treatment
Treatment for PCP involves the use of antibiotics. These include trimethoprim-sulfamethoxazole
(TMP-SMX, Bactrim, Septra) and pentamidine isoethionate (Nebupent, Pentam 300). Both of these
anti-microbial drugs are equally effective. AIDS
patients are typically treated for 21 days, whereas
non-AIDS patients are treated for 14 days. TMPSMX may be highly toxic in AIDS patients, causing
severe side effects that include fever, rash, decreased
numbers of white blood cells and platelets, and hepatitis. Pentamidine also causes side effects in immunocompromised patients. These side effects include
decreased blood pressure, irregular heart beats, the
accumulation of nitrogenous waste products in the
blood (azotemia), and electrolyte imbalances.
Pentamidine can be given in aerosol form to minimize
side effects. Alternative drugs can be used for patients
experiencing these side effects.
P. carinii appears to be developing resistance to
TMP-SMX. In addition, some patients are allergic
to the standard antibiotics given for PCP. As a
result, other antibiotics for the treatment of PCP
are continually under investigation. Some drugs
proven to be effective against P. carinii include
2943

Pneumocystis pneumonia

smaller air tubes (bronchioles) in the lungs. These tiny
air sacs are called alveoli. Under a microscope, alveoli
look like groups of hollow spheres resembling grape
clusters. The exchange of oxygen with the blood takes
place in the alveoli. It appears that P. carinii lives in the
fluid in the lining of the alveoli.

Pneumonia

KEY TERMS
Alveoli—Small, hollow air sacs found in the lungs
at the end of the smaller airways (bronchioles). Air
exchange occurs in the alveoli.
Azotemia—The presence of excess nitrogenous
wastes in the blood.
Biopsy—A procedure in which a piece of tissue is
obtained for microscopic study.
Bronchoscopy—A procedure that uses a fiber-optic
scope to view the airways in the lung.
Fungus—A member of a group of simple organisms
related to yeasts and molds.
Pentamidine isoethionate—An antibiotic used to
treat and prevent PCP.
Pneumocystosis—Another name for active PCP
infection.
Protozoan—A microorganism belonging to the
Protista, which includes the simplest one-celled
organisms.
Sputum—A substance obtained from the lungs and
bronchial tubes by clearing the throat or coughing.
Sputum can be tested for evidence of PCP infection.

are effective in preventing PCP. The drug is, however,
highly toxic. Researchers are currently evaluating the
effectiveness and toxicity of aerosol pentamidine and
dapsone in preventing PCP.
Lifestyle modifications
Patients who have previously had PCP often
experience a recurrence. Healthy lifestyle choices,
including exercising, eating well, and giving up smoking may keep the disease at bay.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Cindy L. A. Jones, PhD

Pneumonectomy see Lung surgery

Trimethoprim-sulfamethoxazole (TMP-SMX)—An
antibiotic used to treat and prevent PCP.

dapsone (DDS) with trimethoprim (Trimpex), clindamycin (Cleocin) with primaquine, as well as atovaquone (Mepron). Paradoxically, corticosteroids
have been found to improve the ability of TMPSMX or pentamidine to treat PCP. As a treatment
of last resort, trimetrexate with leucovorin
(Wellcovorin) can also be used.

Prognosis
If left untreated, PCP will cause breathing difficulties that will eventually cause death. The prognosis
for this disease depends on the amount of damage to
the patient’s lungs prior to treatment. Prognosis is
usually better at a facility that specializes in caring
for AIDS patients. Antibiotic treatment of PCP is
about 80% effective.

Prevention
Medications
For patients at serious risk for PCP infection, low
doses of TMP-SMX, given daily or three times a week,
2944

Pneumonia
Definition
Pneumonia is an infection of the lung that can be
caused by nearly any class of organism known to cause
human infections. These include bacteria, amoebae,
viruses, fungi, and parasites. In the United States,
pneumonia is the sixth most common disease leading
to death; 2 million Americans develop pneumonia
each year, and 40,000–70,000 die from it. Pneumonia
is also the most common fatal infection acquired by
already hospitalized patients. In developing countries,
pneumonia ties with diarrhea as the most common
cause of death. Even in nonfatal cases, pneumonia is
a significant economic burden on the health care system. One study estimates that people in the American
workforce who develop pneumonia cost employers
five times as much in health care as the average
worker.
According to the Centers for Disease Control and
Prevention (CDC), however, the number of deaths
from pneumonia in the United States has declined
slightly since 2001.
GALE ENCYCLOPEDIA OF MEDICINE

Anatomy of the lung
To better understand pneumonia, it is important
to understand the basic anatomic features of the
respiratory system. The human respiratory system
begins at the nose and mouth, where air is breathed
in (inspired) and out (expired). The air tube extending
from the nose is called the nasopharynx. The tube
carrying air breathed in through the mouth is called
the oropharynx. The nasopharynx and the oropharynx merge into the larynx. The oropharynx also carries swallowed substances, including food, water, and
salivary secretion, which must pass into the esophagus and then the stomach. The larynx is protected by
a trap door called the epiglottis. The epiglottis prevents substances that have been swallowed, as well as
substances that have been regurgitated (thrown up),
from heading down into the larynx and toward the
lungs.
A useful method of picturing the respiratory system is to imagine an upside-down tree. The larynx
flows into the trachea, which is the tree trunk, and
thus the broadest part of the respiratory tree. The
trachea divides into two tree limbs, the right and left
bronchi. Each one of these branches off into multiple
smaller bronchi, which course through the tissue of the
lung. Each bronchus divides into tubes of smaller and
smaller diameter, finally ending in the terminal
bronchioles. The air sacs of the lung, in which oxygen-carbon dioxide exchange actually takes place, are
clustered at the ends of the bronchioles like the leaves
of a tree. They are called alveoli.
The tissue of the lung which serves only a supportive role for the bronchi, bronchioles, and alveoli is
called the lung stroma.

Respiratory system defenses
The healthy human lung is sterile. There are no
normally resident bacteria or viruses (unlike the upper
respiratory system and parts of the gastrointestinal
system, where bacteria dwell even in a healthy state).
There are multiple safeguards along the path of the
respiratory system. These are designed to keep invading organisms from leading to infection.
The first line of defense includes the hair in the
nostrils, which serves as a filter for large particles. The
epiglottis is a trap door of sorts, designed to prevent
food and other swallowed substances from entering
the larynx and then trachea. Sneezing and coughing,
both provoked by the presence of irritants within the
respiratory system, help to clear such irritants from the
respiratory tract.
Mucus, produced through the respiratory system,
also serves to trap dust and infectious organisms. Tiny
hair like projections (cilia) from cells lining the respiratory tract beat constantly. They move debris trapped
by mucus upwards and out of the respiratory tract.
This mechanism of protection is referred to as the
mucociliary escalator.
Cells lining the respiratory tract produce several
types of immune substances which protect against
various organisms. Other cells (called macrophages)
along the respiratory tract actually ingest and kill
invading organisms.
The organisms that cause pneumonia, then, are
usually carefully kept from entering the lungs by virtue
of these host defenses. However, when an individual
encounters a large number of organisms at once, the
usual defenses may be overwhelmed, and infection
may occur. This can happen either by inhaling contaminated air droplets, or by aspiration of organisms
inhabiting the upper airways.

Function of the respiratory system
The main function of the respiratory system is
to provide oxygen, the most important energy
source for the body’s cells. Inspired air (the air
you breath in) contains the oxygen, and travels
down the respiratory tree to the alveoli. The oxygen moves out of the alveoli and is sent into circulation throughout the body as part of the red blood
cells. The oxygen in the inspired air is exchanged
within the alveoli for the waste product of human
metabolism, carbon dioxide. The air you breathe
out contains the gas called carbon dioxide. This gas
leaves the alveoli during expiration. To restate this
exchange of gases simply, you breathe in oxygen,
you breathe out carbon dioxide
GALE ENCYCLOPEDIA OF MEDICINE

Conditions predisposing to pneumonia
In addition to exposure to sufficient quantities of
causative organisms, certain conditions may make an
individual more likely to become ill with pneumonia.
Certainly, the lack of normal anatomical structure
could result in an increased risk of pneumonia. For
example, there are certain inherited defects of cilia
which result in less effective protection. Cigarette
smoke, inhaled directly by a smoker or second-hand
by a innocent bystander, interferes significantly with
ciliary function, as well as inhibiting macrophage
function.
Stroke, seizures, alcohol, and various drugs interfere with the function of the epiglottis. This leads to a
2945

Pneumonia

Description

Pneumonia

previously rare parasitic types which would be unable
to cause illness in an individual possessing a normal
immune system.
The elderly have a less effective mucociliary escalator, as well as changes in their immune system. This
causes this age group to be more at risk for the development of pneumonia.
Various chronic conditions predispose a person to
infection with pneumonia. These include asthma, cystic fibrosis, and neuromuscular diseases which may
interfere with the seal of the epiglottis. Esophageal
disorders may result in stomach contents passing
upwards into the esophagus. This increases the risk
of aspiration into the lungs of those stomach contents
with their resident bacteria. Diabetes, sickle cell anemia, lymphoma, leukemia, and emphysema also predispose a person to pneumonia.
Genetic factors also appear to be involved in susceptibility to pneumonia. Certain changes in DNA
appear to affect some patients’ risk of developing
such complications of pneumonia as septic shock.
Pneumonia is also one of the most frequent infectious complications of all types of surgery. Many
drugs used during and after surgery may increase the
risk of aspiration, impair the cough reflex, and cause a
patient to underfill their lungs with air. Pain after
surgery also discourages a patient from breathing deeply enough, and from coughing effectively.
A chest x ray showing lobar pneumonia in the lower lobe of a
patient’s right lung. The alveoli (air sacs) of the lung become
blocked with pus, which forces air out and causes the lung to
become solidified. (Photo Researchers, Inc. Reproduced by
permission.)

Radiation treatment for breast cancer increases
the risk of pneumonia in some patients by weakening
lung tissue.

Causes and symptoms
leaky seal on the trap door, with possible contamination by swallowed substances and/or regurgitated stomach contents. Alcohol and drugs also interfere with
the normal cough reflex. This further decreases the
chance of clearing unwanted debris from the respiratory tract.
Viruses may interfere with ciliary function, allowing themselves or other microorganism invaders (such
as bacteria) access to the lower respiratory tract. One
of the most important viruses is HIV (Human
Immunodeficiency virus), the causative virus in AIDS
(acquired immunodeficiency syndrome). In recent
years this virus has resulted in a huge increase in the
incidence of pneumonia. Because AIDS results in a
general decreased effectiveness of many aspects of the
host’s immune system, a patient with AIDS is susceptible to all kinds of pneumonia. This includes some
2946

The list of organisms which can cause pneumonia
is very large, and includes nearly every class of infecting organism: viruses, bacteria, bacteria-like organisms, fungi, and parasites (including certain worms).
Different organisms are more frequently encountered
by different age groups. Further, other characteristics
of an individual may place him or her at greater risk
for infection by particular types of organisms:


Viruses cause the majority of pneumonias in young
children (especially respiratory syncytial virus, parainfluenza and influenza viruses, and adenovirus).



Adults are more frequently infected with bacteria
(such as Streptococcus pneumoniae, Haemophilus
influenzae, and Staphylococcus aureus).



Pneumonia in older children and young adults is
often caused by the bacteria-like Mycoplasma
GALE ENCYCLOPEDIA OF MEDICINE

air spaces within the lung, instead become solid, due to
quantities of fluid and debris.



Pneumocystis carinii is an extremely important cause
of pneumonia in patients with immune problems
(such as patients being treated for cancer with chemotherapy, or patients with AIDS. Classically considered a parasite, it appears to be more related to
fungi.

Viral pneumonias and mycoplasma pneumonias
do not result in consolidation. These types of pneumonia primarily infect the walls of the alveoli and the
stroma of the lung.



People who have reason to come into contact with
bird droppings, such as poultry workers, are at risk
for pneumonia caused by the organism Chlamydia
psittaci.



A very large, serious outbreak of pneumonia
occurred in 1976, when many people attending an
American Legion convention were infected by a previously unknown organism. Subsequently named
Legionella pneumophila, it causes what is now called
‘‘Legionnaire’s disease.’’ The organism was traced to
air conditioning units in the convention’s hotel.

Pneumonia is suspected in any patient who has
fever, cough, chest pain, shortness of breath, and
increased respirations (number of breaths per minute).
Fever with a shaking chill is even more suspicious.
Many patients cough up clumps of sputum, commonly
known as spit. These secretions are produced in the
alveoli during an infection or other inflammatory condition. They may appear streaked with pus or blood.
Severe pneumonia results in the signs of oxygen deprivation. This includes blue appearance of the nail beds
or lips (cyanosis).
The invading organism causes symptoms, in part,
by provoking an overly-strong immune response in
the lungs. In other words, the immune system, which
should help fight off infections, kicks into such high
gear, that it damages the lung tissue and makes it more
susceptible to infection. The small blood vessels in the
lungs (capillaries) become leaky, and protein-rich fluid
seeps into the alveoli. This results in less functional
area for oxygen-carbon dioxide exchange. The patient
becomes relatively oxygen deprived, while retaining
potentially damaging carbon dioxide. The patient
breathes faster and faster, in an effort to bring in
more oxygen and blow off more carbon dioxide.
Mucus production is increased, and the leaky
capillaries may tinge the mucus with blood. Mucus
plugs actually further decrease the efficiency of gas
exchange in the lung. The alveoli fill further with
fluid and debris from the large number of white
blood cells being produced to fight the infection.
Consolidation, a feature of bacterial pneumonias,
occurrs when the alveoli, which are normally hollow
GALE ENCYCLOPEDIA OF MEDICINE

Severe acute respiratory syndrome (SARS)
Severe acute respiratory syndrome, or SARS, is a
contagious and potentially fatal disease that first
appeared in the form of a multi-country outbreak in
early February 2003. Later that month, the CDC
began to work with the World Health Organization
(WHO) to investigate the cause(s) of SARS and to
develop guidelines for infection control. SARS has
been described as an ‘‘atypical pneumonia of
unknown etiology;’’ by the end of March 2003, the
disease agent was identified as a previously unknown
coronavirus.
The early symptoms of SARS include a high fever
with chills, headache, muscle cramps, and weakness.
This early phase is followed by respiratory symptoms,
usually a dry cough and painful or difficult breathing.
Some patients require mechanical ventilation. The
mortality rate of SARS is thought to be about 3%.
As of the end of March 2003, the CDC did not
have clearly defined recommendations for treating
SARS. Treatments that have been used include antibiotics known to be effective against bacterial pneumonia; ribavirin and other antiviral drugs; and
steroids.

Diagnosis
For the most part, diagnosis is based on the
patient’s report of symptoms, combined with examination of the chest. Listening with a stethoscope will
reveal abnormal sounds, and tapping on the patient’s
back (which should yield a resonant sound due to air
filling the alveoli) may instead yield a dull thump if the
alveoli are filled with fluid and debris.
Laboratory diagnosis can be made of some bacterial pneumonias by staining sputum with special
chemicals and looking at it under a microscope.
Identification of the specific type of bacteria may
require culturing the sputum (using the sputum sample
to grow greater numbers of the bacteria in a lab dish.).
X-ray examination of the chest may reveal certain
abnormal changes associated with pneumonia.
Localized shadows obscuring areas of the lung may
indicate a bacterial pneumonia, while streaky or
2947

Pneumonia

pneumoniae (the cause of what is often referred to as
‘‘walking’’ pneumonia).

Pneumonia

patchy appearing changes in the x-ray picture may
indicate viral or mycoplasma pneumonia. These
changes on x ray, however, are known to lag in time
behind the patient’s actual symptoms.

Treatment
Prior to the discovery of penicillin antibiotics,
bacterial pneumonia was almost always fatal. Today,
antibiotics, especially given early in the course of the
disease, are very effective against bacterial causes of
pneumonia. Erythromycin and tetracycline improve
recovery time for symptoms of mycoplasma pneumonia. They, do not, however, eradicate the organisms.
Amantadine and acyclovir may be helpful against certain viral pneumonias.
A newer antibiotic named linezolid (Zyvox) is
being used to treat penicillin-resistant organisms that
cause pneumonia. Linezolid is the first of a new line of
antibiotics known as oxazolidinones. Another new
drug known as ertapenem (Invanz) is reported to be
effective in treating bacterial pneumonia.

Prognosis
Prognosis varies according to the type of organism causing the infection. Recovery following pneumonia with Mycoplasma pneumoniae is nearly 100%.
Staphylococcus pneumoniae has a death rate of
30–40%. Similarly, infections with a number of gram
negative bacteria (such as those in the gastrointestinal
tract which can cause infection following aspiration)
have a death rate of 25–50%. Streptococcus pneumoniae, the most common organism causing pneumonia,
produces a death rate of about 5%. More complications occur in the very young or very old individuals
who have multiple areas of the lung infected simultaneously. Individuals with other chronic illnesses
(including cirrhosis of the liver, congestive heart
failure, individuals without a functioning spleen, and
individuals who have other diseases that result in a
weakened immune system, experience complications.
Patients with immune disorders, various types of cancer, transplant patients, and AIDS patients also
experience complications.

KEY TERMS
Alveoli—The little air sacs clustered at the ends of
the bronchioles, in which oxygen-carbon dioxide
exchange takes place.
Aspiration—A situation in which solids or liquids
which should be swallowed into the stomach are
instead breathed into the respiratory system.
Cilia—Hair-like projections from certain types of
cells.
Consolidation—A condition in which lung tissue
becomes firm and solid rather than elastic and airfilled because it has accumulated fluids and tissue
debris.
Coronavirus—One of a family of RNA-containing
viruses known to cause severe respiratory illnesses.
In March 2003, a previously unknown coronavirus
was identified as the causative agent of severe
acute respiratory syndrome, or SARS.
Cyanosis—A bluish tinge to the skin that can occur
when the blood oxygen level drops too low.
Sputum—Material produced within the alveoli in
response to an infectious or inflammatory process.
Stroma—A term used to describe the supportive
tissue surrounding a particular structure. An example is that tissue which surrounds and supports the
actually functional lung tissue.

fibrosis, other lung or heart diseases, sickle cell disease,
diabetes, kidney disease, and forms of cancer).
A specific vaccine against Streptococcus pneumoniae is very protective, and should also be administered to patients with chronic illnesses.
Patients who have decreased immune resistance
are at higher risk for infection with Pneumocystis carinii. They are frequently put on a regular drug regimen
of trimethoprim sulfa and/or inhaled pentamidine to
avoid pneumocystis pneumonia.
Resources
BOOKS

Prevention
Because many bacterial pneumonias occur in
patients who are first infected with the influenza
virus (the flu), yearly vaccination against influenza
can decrease the risk of pneumonia for certain
patients. This is particularly true of the elderly and
people with chronic diseases (such as asthma, cystic
2948

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Pneumonia.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Arias, E., and B. L. Smith. ‘‘Deaths: Preliminary Data for
2001.’’ National Vital Statistics Reports 51 (March 14,
2003): 1–44.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

pressure in the pleura then becomes greater than
the pressure in the lungs, causing the lung to collapse
partially or completely. Pneumothorax can be either
spontaneous or due to trauma.
If a pneumothorax occurs suddenly or for no
known reason, it is called a spontaneous pneumothorax. This condition most often strikes tall,
thin men between the ages of 20 to 40. In addition,
people with lung disorders, such as emphysema, cystic fibrosis, and tuberculosis, are at higher risk for
spontaneous pneumothorax. Traumatic pneumothorax is the result of accident or injury due to
medical procedures performed to the chest cavity,
such as thoracentesis or mechanical ventilation.
Tension pneumothorax is a serious and potentially
life-threatening condition that may be caused by
traumatic injury, chronic lung disease, or as a complication of a medical procedure. In this type of
pneumothorax, air enters the chest cavity, but cannot
escape. This greatly increased pressure in the pleural
space causes the lung to collapse completely, compresses the heart, and pushes the heart and associated
blood vessels toward the unaffected side.

Causes and symptoms
The symptoms of pneumothrax depend on how
much air enters the chest, how much the lung collapses, and the extent of lung disease. Symptoms
include the following, according to the cause of the
pneumothorax:


Spontaneous pneumothorax. Simple spontaneous
pneumothorax is caused by a rupture of a small air
sac or fluid-filled sac in the lung. It may be related to
activity in otherwise healthy people or may occur
during scuba diving or flying at high altitudes.
Complicated spontaneous pneumothorax, also generally caused by rupture of a small sac in the lung,
occurs in people with lung diseases. The symptoms of
complicated spontaneous pneumothorax tend to be
worse than those of simple pneumothorax, due to the
underlying lung disease. Spontaneous pneumothorax is characterized by dull, sharp, or stabbing
chest pain that begins suddenly and becomes worse
with deep breathing or coughing. Other symptoms
are shortness of breath, rapid breathing, abnormal
breathing movement (that is, little chest wall movement when breathing), and cough.



Tension pneumothorax. Following trauma, air may
enter the chest cavity. A penetrating chest wound
allows outside air to enter the chest, causing the
lung to collapse. Certain medical procedures performed in the chest cavity, such as thoracentesis,

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

Pneumonitis see Pneumonia

Pneumothorax
Definition
Pneumothorax is a collection of air or gas in the
chest or pleural space that causes part or all of a lung
to collapse.

Description
Normally, the pressure in the lungs is greater than
the pressure in the pleural space surrounding the
lungs. However, if air enters the pleural space, the
GALE ENCYCLOPEDIA OF MEDICINE

2949

Pneumothorax

Birnbaum, Howard G., Melissa Morley, Paul E. Greenberg,
et al. ‘‘Economic Burden of Pneumonia in an Employed
Population.’’ Archives of Internal Medicine 161
(December 10, 2001): 2725-2732.
Curran, M., D. Simpson, and C. Perry. ‘‘Ertapenem: A
Review of Its Use in the Management of Bacterial
Infections.’’ Drugs 63 (2003): 1855–1878.
Lyseng-Williamson, K. A., and K. L. Goa. ‘‘Linezolid: In
Infants and Children with Severe Gram-Positive
Infections.’’ Paediatric Drugs 5 (2003): 419–429.
‘‘New Research Shows That Pneumonia, Septic Shock Run
in Families.’’ Genomics & Genetics Weekly November
16, 2001: 13.
‘‘Outbreak of Severe Acute Respiratory Syndrome—
Worldwide, 2003.’’ Morbidity and Mortality Weekly
Report 52 (March 21, 2003): 226–228.
‘‘Update: Outbreak of Severe Acute Respiratory
Syndrome—Worldwide, 2003.’’ Morbidity and
Mortality Weekly Report 52 (March 28, 2003):
241–246, 248.
Worcester, Sharon. ‘‘Ventilator-Linked Pneumonia.’’
Internal Medicine News 34 (October 15, 2001): 32.
Wunderink, R. G., S. K. Cammarata, T. H. Oliphant, et al.
‘‘Continuation of a Randomized, Double-Blind,
Multicenter Study of Linezolid Versus Vancomycin in
the Treatment of Patients with Nosocomial
Pneumonia.’’ Clinical Therapeutics 25 (March 2003):
980–992.

Pneumothorax

KEY TERMS
Electrocardiagram—A test that provides a typical
record of normal heart action.
Mediastinum—The space between the right and
left lung.
Pleural—Pleural refers to the pleura or membrane
that enfolds the lungs.
Thoracentesis—Also called a pleural fluid tap, this
procedure involves aspiration of fluid from the
pleural space using a long, thin needle inserted
between the ribs.

Treatment

An x ray of a patient undergoing pneumothorax treatment.
ECG electrodes attached to chest monitor heartbeat while
endotracheal tube is inserted in windpipe. (Photo
Researchers. Reproduced by permission.)

also may cause a lung to collapse. Tension pneumothorax may be the immediate result of an injury;
the delayed complication of a hidden injury, such as
a fractured rib, that punctures the lung; or the result
of lung damage from asthma, chronic bronchitis, or
emphysema. Symptoms of tension pneumothorax
tend to be severe with sudden onset. There is marked
anxiety, distended neck veins, weak pulse, decreased
breath sounds on the affected side, and a shift of the
mediastinum to the opposite side.

Diagnosis
To diagnose pneumothorax, it is necessary for the
health care provider to listen to the chest (auscultation) during a physical examination. By using a stethoscope, the physician may note that one part of the
chest does not transmit the normal sounds of breathing. A chest x ray will show the air pocket and the
collapsed lung. An electrocardiogram (ECG) will be
performed to record the electrical impulses that
control the heart’s activity. Blood samples may be
taken to check for the level of arterial blood gases.
2950

A small pneumothorax may resolve on its own,
but most require medical treatment. The object of
treatment is to remove air from the chest and allow
the lung to re-expand. This is done by inserting a
needle and syringe (if the pneumothorax is small) or
chest tube through the chest wall. This allows the air to
escape without allowing any air back in. The lung will
then re-expand itself within a few days. Surgery may
be needed for repeat occurrences.

Prognosis
Most people recover fully from spontaneous pneumothorax. Up to half of patients with spontaneous
pneumothorax experience recurrence. Recovery from a
collapsed lung generally takes one to two weeks. Tension
pneumothorax can cause death rapidly due to inadequate heart output or insufficient blood oxygen (hypoxemia), and must be treated as a medical emergency.

Prevention
Preventive measures for a non-injury related
pneumothorax include stopping smoking and seeking
medical attention for respiratory problems. If the
pneumothorax occurs in both lungs or more than
once in the same lung, surgery may be needed to prevent it from occurring again.
Resources
ORGANIZATIONS

American Association for Respiratory Care. 11030 Ables
Lane, Dallas, Texas 75229. (972) 243-2272. <http://
www.aarc.org>.
American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Spontaneous Pneumothorax.’’ HealthAnswers.com.
<http://www.healthanswers.com>.

Lorraine Steefel, RN

Podiatry see Foot care

animals are rarely affected, they can carry the resin on
their fur and transfer it to humans. According to the
experts at the University of Maryland Medical Center,
the ‘‘chemical [resin] can remain active for more than a
year.’’
The symptoms for poison ivy and poison oak are
the same. Usually the first symptoms to appear are
itchiness and swelling in the areas of contact. The itchy
rash that follows is made up of small pimple-like
bumps (sometimes referred to as papules), as well as
blisters that later break open, ooze, and crust over.

Poison ivy and poison oak
Definition
Poison ivy and poison oak are plants that cause an
allergic skin reaction in most people who are exposed
to them.

Description
Poison ivy, which is generally thought of as a
climbing vine, can also grow as a shrub or bush. It
has leaves that are elliptical in shape and grow in
groups of three on a stem. Poison ivy is common in
the United States, except in the southwest, Alaska,
and Hawaii. Poison oak, which grows as a shrub, has
leaves that are shaped like oak leaves and also grow in
groups of three to a stem. Poison oak is common in the
United States, especially on the west coast from
Mexico to Canada.
Not everyone is sensitive to poison ivy and poison oak; however, nine out of ten people who come in
contact with either of the plants will have an allergic
reaction to some degree. All parts of the plants are
poisonous and the amount of time it takes for an
allergic reaction to develop varies from person to
person. The extent and severity of the reaction
depends on the length of exposure, type of contact,
and how sensitive the person is to the plants. If a
person is going to have an allergic reaction, it will
usually occur within one or two days of exposure.
However, some people have a reaction within an
hour, whereas others don’t experience a reaction
until five days after the exposure.

Causes and symptoms
The substance that causes the allergic reaction is
the same for both plants. It is an oily resin called
urushiol. It only takes a small amount of the resin to
cause a reaction. The resin can be transferred to the
skin by directly touching the plant or indirectly by
coming in contact with something that has touched
the plant, such as tools, animals, or clothing. Although
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
A diagnosis is made based on the symptoms and a
physical examination of the patient.
In some cases, people have jobs that make it difficult for them to avoid poison ivy and poison oak, such
as people who work in wooded areas or on construction sites, for example. Employees without health
insurance may be covered by workers compensation.

Treatment
Anyone who comes in contact with either plant
should wash the exposed area with soap and water
immediately. Taking a bath immediately after contact is not recommended, because that could
spread the resin to other areas of the body. All
clothing, including shoes and shoelaces, should be
removed carefully and either washed separately or
discarded.
For minor cases, hydrocortisone cream and
Calamine lotion can provide relief until the symptoms
disappear. Over-the-counter Benadryl capsules help
with the itching. Some people find oatmeal or baking
soda baths to be soothing as well. Oral steroids, such
as prednisone, are available for more serious cases,
especially those affecting the face, eyes, mouth, or
genitals. If signs of infection develop, such as pus
and a fever, patients should contact their doctors.
Patients should consult their physicians before
they use any ointments that contain benzocaine or
zirconium, because they can cause an allergic reaction
that worsens the condition. Antihistamine ointments
are not recommended for the same reason. The experts
at the Alabama Cooperative Extension System caution that ‘‘some people have severe allergic reactions
to these plants and can have swelling in the throat,
breathing problems, weakness, dizziness, and bluish
lips.’’ Emergency medical care should be sought if
any serious reactions occur.
2951

Poison ivy and poison oak

OTHER

Poisoning

Prognosis
In most cases, the condition goes away in two
weeks.

Prevention
The best prevention is know what the plants look
like and to avoid them. A common saying should be
kept in mind: Leaves of three, let them be.
People who plan to be in an area where poison ivy
and poison oak might be found should wear protective
clothing, such as long-sleeved shirts and long pants.
Eradication of the plants should be handled with
care. As stated by the experts at the Alabama
Cooperative Extension System, ‘‘burning can be dangerous and is not recommended for disposal or as a
control measure, because the toxic oil from the plant
can be carried in the smoke.’’ Instead they recommend
spraying the plants with glyphosate, which is commonly known as the brands Roundup or Kleenup.
Resources
OTHER

Common Pesky Plants: Poison Ivy & Poison Oak Alabama
Cooperative Extension. [cited march 19, 2005].
<http://www.aces.edu/Tallapoosa/weed-control/poison-ivy.htm>.
Poison Ivy University of Maryland Medical Center. [cited
march 19, 2005]. <http://www.umm.edu/>.

Lee Ann Paradise

Poisoning
Definition
Poisoning occurs when any substance interferes
with normal body functions after it is swallowed,
inhaled, injected, or absorbed. The branch of medicine
that deals with the detection and treatment of poisons
is known as toxicology.

Description
Poisonings are a common occurrence. About 10
million cases of poisoning occur in the United States
each year. In 80% of the cases, the victim is a child
under the age of five. About 50 children die each year
from poisonings. Curiosity, inability to read warning
2952

labels, a desire to imitate adults, and inadequate supervision lead to childhood poisonings.
The elderly are the second most likely group to be
poisoned. Mental confusion, poor eyesight, and the
use of multiple drugs are the leading reasons why this
group has a high rate of accidental poisoning. A substantial number of poisonings also occur as suicide
attempts or drug overdoses.
Poisons are common in the home and workplace,
yet there are basically two major types. One group
consists of products that were never meant to be
ingested or inhaled, such as shampoo, paint thinner,
pesticides, houseplant leaves, and carbon monoxide.
The other group contains products that can be
ingested in small quantities, but which are harmful if
taken in large amounts, such as pharmaceuticals, medicinal herbs, or alcohol. Other types of poisons include
the bacterial toxins that cause food poisoning, such as
Escherichia coli; heavy metals, such as the lead found
in the paint on older houses; and the venom found in
the bites and stings of some animals and insects. The
staff at a poison control center and emergency room
doctors have the most experience diagnosing and
treating poisoning cases.

Causes and symptoms
The effects of poisons are as varied as the poisons
themselves; however, the exact mechanisms of only a
few are understood. Some poisons interfere with the
metabolism. Others destroy the liver or kidneys, such
as heavy metals and some pain relief medications,
including acetaminophen (Tylenol) and nonsteroidal
anti-inflammatory drugs (Advil, Ibuprofen). A poison
may severely depress the central nervous system, leading to coma and eventual respiratory and circulatory
failure. Potential poisons in this category include anesthetics (e.g. ether and chloroform), opiates (e.g., morphine and codeine), and barbiturates. Some poisons
directly affect the respiratory and circulatory system.
Carbon monoxide causes death by binding with hemoglobin that would normally transport oxygen
throughout the body. Certain corrosive vapors trigger
the body to flood the lungs with fluids, effectively
drowning the person. Cyanide interferes with respiration at the cellular level. Another group of poisons
interferes with the electrochemical impulses that travel
between neurons in the nervous system. Yet another
group, including cocaine, ergot, strychnine, and some
snake venoms, causes potentially fatal seizures.
Severity of symptoms can range from headache
and nausea to convulsions and death. The type of
poison, the amount and time of exposure, and the
GALE ENCYCLOPEDIA OF MEDICINE

Poisoning

Common Household, Industrial, And Agricultural Products Containing Toxic Sustances

Alcohol (rubbing)
Arsenic
Glues/adhesives
Batteries, automotive
Mercury
Cleaning products
Mothballs
Daffodil bulbs
Paints, oil-based or alkyds
Drain openers
English nightshade
Strychnine

FuelAntifreeze
Gasoline
Automotive fluids
Kerosene
Building products
Metalworking materials
Cyanide
Paint strppers/thinners
Disinfectants/air fresheners
Pesticides
Stains/finishes
Foxglove

age, size, and health of the victim are all factors which
determine the severity of symptoms and the chances
for recovery.
Plant poisoning
There are more than 700 species of poisonous
plants in the United States. Plants are second only to
medicines in causing serious poisoning in children
under age five. There is no way to tell by looking at a
plant if it is poisonous. Some plants, such as the yew
shrub, are almost entirely toxic: needles, bark, seeds,
and berries. In other plants, only certain parts are
poisonous. The bulb of the hyacinth and daffodil
are toxic, but the flowers are not; while the flowers of
the jasmine plant are the poisonous part. Moreover,
some plants are confusing because portions of them
are eaten as food while other parts are poisonous. For
example, the fleshy stem (tuber) of the potato plant is
nutritious; however, its roots, sprouts, and vines are
poisonous. The leaves of tomatoes are poisonous,
while the fruit is not. Rhubarb stalks are good to eat,
but the leaves are poisonous. Apricots, cherries,
peaches, and apples all produce healthful fruit, but
their seeds contain a form of cyanide that can kill a
child if chewed in sufficient quantities. One hundred
milligrams (mg) of moist, crushed apricot seeds can
produce 217 mg of cyanide.
Common houseplants that contain some poisonous parts include:



Bird of paradise flower



Buttercup



Castor bean



Chinaberry tree



Daffodil



English ivy



Eucalyptus



Foxglove



Holly



Horse chestnut



Iris



Jack-in-the-pulpit



Jimsonweed (also called thornapple)



Larkspur



Lily-of-the-valley



Morning glory



Nightshade (several varieties)



Oleander



Potato



Rhododendron



Rhubarb



Sweet pea



Aloe



Tomato



Amaryllis



Wisteria



Cyclamen



Yew



Dumb cane (also called Dieffenbachia)



Philodendron

Common outdoor plants that contain some poisonous part include:
GALE ENCYCLOPEDIA OF MEDICINE

Floor/furniture polish
Art and craft supplies
Hemlock
Batteries, household
Metal primers
Cosmetics/personal care items
Oven cleaners
Dieffenbachia
Paints, water-based or latex
Flea collars/insect repellent
Ethanol
Wood preservatives

Symptoms of plant poisoning range from irritation of the skin or mucous membranes of the mouth
and throat to nausea, vomiting, convulsions, irregular
heartbeat, and even death. It is often difficult to tell if a
person has eaten a poisonous plant because there are
2953

Poisoning

no tell-tale empty containers and no unusual lesions or
odors around the mouth.
Many cases of plant poisoning involve plants that
contain hallucinogens, such as peyote cactus buttons,
certain types of mushrooms, and marijuana. A recent
case of plant poisoning in France concerned Datura,
or moonflower, a plant that has become popular with
young people trying to imitate Native American puberty rites.
Other cases of plant poisoning result from the use
of herbal dietary supplements that have been contaminated by toxic substances. The Food and Drug
Administration (FDA) has the authority to monitor
herbal products on the market and issue warnings
about accidental poisoning or other adverse affects
associated with these products. For example, in 2002
a manufacturer of nettle capsules found to contain
lead recalled the product following a warning from
the FDA. Other dietary supplements have been
found to contain small quantities of prescription medications or even toxic plants.
Household chemicals
Many products used daily in the home are poisonous if swallowed. These products often contain
strong acids or strong bases (alkalis). Toxic household
cleaning products include:

nearby, nausea or vomiting, and burns on the lips
and skin around the mouth if the substance was a
strong acid or alkali. The chemicals in some of these
products may leave a distinctive odor on the breath.
Pharmaceuticals
Both over-the-counter and prescription medicines
can help the body heal if taken as directed. However,
when taken in large quantities, or with other drugs
where there may be an adverse interaction, they can
act as poisons. Drug overdoses, both accidental and
intentional, are the leading cause of poisoning in
adults. Medicinal herbs should be treated like pharmaceuticals and taken only in designated quantities
under the supervision of a knowledgeable person.
Herbs that have healing qualities when taken in small
doses can be toxic in larger doses, or may interact with
prescription medications in unpredictable ways.
Drug overdoses cause a range of symptoms,
including excitability, sleepiness, confusion, unconsciousness, rapid heartbeat, convulsions, nausea, and
changes in blood pressure. The best initial evidence of
a drug overdose is the presence of an empty container
near the victim.
Other causes of poisonings



ammonia



bleach



dishwashing liquids

People can be poisoned by fumes they inhale.
Carbon monoxide is the most common form of
inhaled poison. Other toxic substances that can be
inhaled include:



drain openers



farm and garden insecticides and herbicides



floor waxes and furniture polishes



gasoline fumes



laundry detergents, spot cleaners, and fabric
softeners



insect repellent

mildew removers



paint thinner fumes




oven cleaners



toilet bowl cleaners

Personal care products found in the home can also
be poisonous. These include:


deodorant



hairspray



hair straighteners



nail polish and polish remover



perfume



shampoo

Signs that a person has swallowed one of these
substances include evidence of an empty container
2954

Diagnosis
Initially, poisoning is suspected if the victim shows
changes in behavior and signs or symptoms previously
described. Hallucinations or other psychiatric symptoms may indicate poisoning by a hallucinogenic
plant. Evidence of an empty container or information
from the victim are helpful in determining exactly
what substance has caused the poisoning. Some acids
and alkalis leave burns on the mouth. Petroleum products, such as lighter fluid or kerosene, leave a distinctive odor on the breath. The vomit may be tested to
determine the exact composition of the poison. Once
hospitalized, the patient may be given blood and urine
tests to determine his or her metabolic condition.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Treatment for poisoning depends on the poison
swallowed or inhaled. Contacting the poison control
center or hospital emergency room is the first step in
getting proper treatment. The poison control center’s
telephone number is often listed with emergency numbers on the inside cover of the telephone book, or it
can be reached by dialing the operator. The poison
control center will ask for specific information about
the victim and the poison, then give appropriate first
aid instructions. If the patient is to be taken to a
hospital, a sample of vomit and the poison container
should be taken along, if they are available.

Antidote—A medication or remedy for counteracting the effects of a poison.
Emetic—A medication or substance given to
induce vomiting.
Gastric lavage—A technique for washing poison
out of the stomach by instilling water or saline
solution through a tube, removing the stomach
contents by suction, and repeating the process
until the washings are free of poison. It is also called
stomach pumping.
Toxicology—The branch of medicine that deals
with the effects, detection, and treatment of
poisons.

Most cases of plant poisoning are treated by inducing vomiting, if the patient is fully conscious.
Vomiting can be induced by taking syrup of ipecac,
an over-the-counter emetic available at any pharmacy.
For acid, alkali, or petroleum product poisonings,
the patient should not vomit. Acids and alkalis can
burn the esophagus if they are vomited, and petroleum
products can be inhaled into the lungs during vomiting, resulting in pneumonia.
Once under medical care, doctors have the option
of treating the patient with a specific remedy to counteract the poison (antidote) or with activated charcoal
to absorb the substance inside the patient’s digestive
system. In some instances, pumping the stomach may
be required. This technique, which is known as gastric
lavage, involves introducing 20–30 mL of tap water or
9% saline solution into the patient’s digestive tract
and removing the stomach contents with a siphon or
syringe. The process is repeated until the washings are
free of poison. Medical personnel will also provide
supportive care as needed, such as intravenous fluids
or mechanical ventilation.
If the doctor suspects that the poisoning was not
accidental, he or she is required to notify law enforcement authorities. Most cases of malicious poisoning
concern family members or acquaintances of the victim, but the number of intentional random poisonings
of the general public has increased in recent years. A
case reported in 2003 involved the use of nicotine to
poison 1700 pounds of ground beef in a Michigan
supermarket. Over a hundred persons fell ill after eating the poisoned beef.

Prognosis
The outcome of poisoning varies from complete
recovery to death, and depends on the type and
amount of the poison, the health of the victim, and
the speed with which medical care is obtained.
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Most accidental poisonings are preventable. The
number of deaths of children from poisoning has
declined from about 450 per year in the 1960s to
about 50 each year in the 1990s. This decline has
occurred mainly because of better packaging of toxic
materials and better public education.
Actions to prevent poisonings include:


removing plants that are poisonous



keeping medicines and household chemicals locked
and in a place inaccessible to children



keeping medications in child-resistant containers



never referring to medicine as ‘‘candy’’



keeping cleaners and other poisons in their original
containers



disposing of outdated prescription medicines



not purchasing over-the-counter medications with
damaged protective seals or packaging



avoiding the use of herbal preparations not made by
a reputable manufacturer

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Poisoning.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Arouko, H., M. D. Matray, C. Braganca, et al. ‘‘Voluntary
Poisoning by Ingestion of Datura stramonium. Another
Cause of Hospitalization in Youth Seeking Strong
2955

Poisoning

Treatment

Polarity therapy

Sensations.’’ [in French] Annales de me´decine interne
154, Spec no. 1 (June 2003): S46–S50.
Centers for Disease Control and Prevention. ‘‘Nicotine
Poisoning After Ingestion of Contaminated Ground
Beef—Michigan, 2003. ’’ Morbidity and Mortality
Weekly Report 52 (May 9, 2003): 413–416.
Hirshon, Jon Mark, MD, MPH. ‘‘Plant Poisoning, Herbs.’’
eMedicine January 18, 2002. <http://www.emedicine.com/EMERG/topic449.htm>.
Salomone, Joseph A., III, MD. ‘‘Toxicity, Hallucinogen.’’
eMedicine November 27, 2001. <http:///www.emedicine.com/emerg/topic223.htm>.
ORGANIZATIONS

American Association of Poison Control Centers (AAPCC).
3201 New Mexico Avenue, Suite 330, Washington, DC
20016. (202) 362-7217. POISONING
EMERGENCIES: (800) 222-1222. <http://
www.aapcc.org>.
National Toxicology Program (NTP) of the National
Institute of Environmental Health Sciences (NIEHS).
P. O. Box 12233, Research Triangle Park, NC 27709.
(919) 541-3419. <http://www.ntpserver.niehs.nih.gov>.
U. S. Food and Drug Administration (FDA). 5600 Fishers
Lane, Rockville, MD 20857. (888) 463-6332. <http://
www.fda.gov>.
OTHER

Arizona Poison and Drug Information Center Page. <http://
www.pharmacy.arizona.edu/centers/poisoncenter>.
‘‘Homeowner Chemical Safety.’’ Centers for DiseaseControl.
<http://www.cdc.gov/niosh/nasd/docs2/pdfs/
as23900.pdf>.
‘‘Poisonous Plant Databases.’’ University of Maryland.
<http://www.inform.umd.edu>.

Tish Davidson, A.M.
Rebecca J. Frey, PhD

Polarity therapy
Definition
Polarity therapy is a holistic, energy-based system
that includes bodywork, diet, exercise, and lifestyle
counseling for the purpose of restoring and maintaining proper energy flows throughout the body. The
underlying concept of polarity therapy is that all
energy within the human body is based in electromagnetic force and that disease results from improperly
dissipated energy.
2956

Purpose
Polarity therapy unblocks and recharges the flow
of life energy and realigns unbalanced energy as a
means of eliminating disease. Patients learn to release
tension by addressing the source of the stress and by
maintaining a healthy demeanor accordingly.
This treatment may be effective to promote health
and healing to anyone willing to embrace the appropriate lifestyle. Polarity therapy is reportedly effective
for anyone who has been exposed to toxic poisons.
Likewise, HIV-positive individuals may find comfort
in polarity therapy. Additionally this is an appropriate
therapy for relieving general stress, back pain, stomach
cramps, and other recurring maladies and conditions.

Description
Origins
Austrian-American chiropractor, osteopath, and
naturopath Randolph Stone (1888–1981) developed
polarity therapy as an integration of Eastern and
Western principles and techniques of healing. Stone
discovered the ancient principles of the Ayurvedic
philosophy in the course of his travels during a sojourn
in India. On a life-long quest to learn the fundamentals
of human vitality, he also studied reflexology and
traditional Chinese medicine.
Stone became committed to the principles of
Ayurvedic medicine, which he interpreted in conjunction with his scientific and medical knowledge to define
polarity therapy. According to the philosophy of
Ayurved, which is based in a set of principles called
the tridosha—the energy of the human body is centered
in five organs or regions (the brain; the cardiopulmonary [heart and lungs] region, the diaphragm, the smaller
intestine, and the larger intestine). One of five airs or
energy forms controls each respective region: prana in
the brain, vyana in the heart and lungs, udana in the
diaphragm, samana in the smaller intestine, and apana
in the larger intestine. The five airs control all directional motion in the body, with each air in command of
a different type of movement. Stone established further
that the prana, centered in the brain, ultimately controlled the combined forces of the body. Any impediment or restriction to the flow of prana in turn affects
the health of the entire body. The prana force is nurtured through the flow of food and air into the body as
well as through our interactions with other living beings
and through the intake of the five sensory organs.
Stone devoted much of his life to defining an
elaborately detailed cause and effect relationship
between the human anatomy and illness, based on
GALE ENCYCLOPEDIA OF MEDICINE

After determining the exact source of a patient’s
energy imbalance, the therapist begins the first of a series
of bodywork sessions designed to rechannel and release
the patient’s misdirected prana. This therapy, akin to
massage, is based in energetic pressure and involves circulating motions. In performing the regimen, the therapist pays strict attention to the pressure exerted at each
location—even to which finger is used to apply pressure
at any given point of the patient’s anatomy. This technique, which comprises the central regimen or focal point
of polarity therapy is very gentle and is unique to polarity
therapy. It typically involves subtle rocking movements
and cranial holds to stimulate body energy. Although
firm, deep pushing touches are employed in conjunction
with the massage technique, the polarity therapist never
exerts a particularly forceful contact.
To support the bodywork, the therapist often prescribes a diet for the patient, to encourage cleansing
and eliminate waste. The precepts of polarity therapy
take into consideration specific interactions between
different foods and the human energy fields.
Likewise, a series of exercises is frequently prescribed. These exercises, called polarity yoga include
squats, stretches, rhythmic movements, deep breathing, and expression of sounds. They can be both energizing and relaxing. Counseling may be included
whenever appropriate as a part of a patient’s highly
individual therapy regimen to promote balance.

Preparations
Therapists take a comprehensive case history
from every patient prior to beginning treatment. This
preliminary verbal examination often monopolizes the
first therapy session. Depending upon circumstances,
a therapist might have a need to assess the patient’s
physical structural balance through observation and
physical examination.

KEY TERMS
Apana—Life sustaining energy centered in the larger
intestine; the fifth of the five airs of Ayurvedic philosophy; the life force governing expulsion activity.
Ayurveda—(Sanskrit, Ayur, life, and veda, knowledge) Translated as ‘‘knowledge of life’’ or
‘‘science of longevity.’’ It became established as
the traditional Hindu system of medicine.
Caduceus—The ancient and universal symbol of
medicine consisting of the winged staff of
Mercury and two intertwining serpents.
Primary energy pattern—A spiral motion that radiates from the umbilicus; the energy pattern associated with a child in the womb.
Prana—Life sustaining energy centered in the
human brain; the first of the five airs of Ayurvedic
philosophy; the life force governing inspiration and
the conscious intellect.
QV—Quantum vacuum, a theory coined by physicists, which defines the interactions of energy that
combine to form reality.
Reflexology—Belief that reflex areas in the feet
correspond to every part of the body, including
organs and glands, and that stimulating the correct
reflex area can affect the body part.
Samana—Life sustaining energy of the smaller intestine; the fourth of the five airs of Ayurvedic philosophy; the life force governing side-to-side motion.
Tridosha—The combination of three basic principles of energy, or biological humor, that comprise
life, according to Ayurvedic philosophy.
Udana—Life sustaining energy of the diaphragm,
the third of the five airs of Ayurvedic philosophy,
the life force governing upward motion.
Vyana—Life sustaining energy of the heart and
lungs; the second of the five airs of Ayurvedic philosophy; the life force governing circular motion.

Side effects
Highly emotional releases of energy (laughter,
tears, or a combination of both) are associated with
this therapy.

Precautions
Polarity therapy is safe for virtually anyone, even
the elderly and the most frail patients, because of the
intrinsic gentleness of the massage therapy.
GALE ENCYCLOPEDIA OF MEDICINE

Research and general acceptance
This is a complementary therapy of holistic, spiritually based treatment, which may be used in
2957

Polarity therapy

the energy flow of the prana. He further attributed
electromagnetic energy as the basis of the energy
forces. He used the medical symbol of the Caduceus
to define the patterns of the flow and described the
energy movement in detail in charts of the human
body. Polarity therapy is based in charted energy
flows. The primary energy pattern is defined in a spiral
motion that radiates from the umbilicus and defines
the original energy flow of the fetus in the womb.

Polio

conjunction with a medical approach. Polarity therapy is practiced worldwide, but the majority of practitioners are based in the United States. Modern
physicists employ concepts similar to Stone’s basic
theories of polarity in defining the quantum vacuum
(QV) as a foundation of all reality. Still, by 2000, this
holistic regimen had not achieved the widespread
acceptance anticipated by Stone before his death
in 1981.
When St. Paul Fire and Marine insurers offered a
liability insurance package to therapy providers, the
company recognized polarity therapy as an alternative
medical treatment along with acupuncture, biofeedback, homeopathy, reflexology, and others.
Resources
PERIODICALS

Modern Medicine August 1, 1999: 15.
ORGANIZATIONS

American Polarity Therapy Association. P.O. Box 19858,
Boulder Colorado 80308. (303) 545-2080. Fax: (303)
545-2161.
Trans-Hyperboreau Institute of Science. P.O. Box 2344
Sausalito, California 94966. (415) 331-0230. (800) 4858095. Fax: (415) 331-0231.
OTHER

Young, Phil. ‘‘Prana.’’ June 16, 2000. <http://www.eclipse.co.uk/masterworks/Polarity/PolarityArticles.htm>.

Gloria Cooksey

Polio
Definition
Poliomyelitis, also called polio or infantile paralysis, is a highly infectious viral disease that may attack
the central nervous system and is characterized by
symptoms that range from a mild nonparalytic infection to total paralysis in a matter of hours.

Description
There are three known types of polioviruses (called
1,2, and 3), each causing a different strain of the disease
and all are members of the viral family of enteroviruses
(viruses that infect the gastrointestinal tract). Type 1 is
the cause of epidemics and many cases of paralysis, which
is the most severe manifestation of the infection. The
virus is usually a harmless parasite of human beings.
2958

Some statistics quote one in 200 infections as leading to
paralysis while others state that one in 1,000 cases reach
the central nervous system (CNS). When it does reach the
CNS, inflammation and destruction of the spinal cord
motor cells (anterior horn cells) occurs, which prevents
them from sending out impulses to muscles. This causes
the muscles to become limp or soft and they cannot
contract. This is referred to as flaccid paralysis and is
the type found in polio. The extent of the paralysis
depends on where the virus strikes and the number of
cells that it destroys. Usually, some of the limb muscles
are paralyzed; the abdominal muscles or muscles of the
back may be paralyzed, affecting posture. The neck muscles may become too weak for the head to be lifted.
Paralysis of the face muscles may cause the mouth to
twist or the eyelids to droop. Life may be threatened if
paralysis of the throat or of the breathing muscles occurs.
Man is the only natural host for polioviruses and
it most commonly infects younger children, although
older children and adults can be infected. Crowded
living conditions and poor hygiene encourage the
spread of poliovirus. Risk factors for this paralytic
illness include older age, pregnancy, abnormalities of
the immune system, recent tonsillectomy, and a recent
episode of excessively strenuous exercise concurrent
with the onset of the CNS phase.

Causes and symptoms
Poliovirus can be spread by direct exposure to an
infected individual, and more rarely, by eating foods
contaminated with waste products from the intestines
(feces) and/or droplets of moisture (saliva) from an
infected person. Thus, the major route of transmission
is fecal-oral, which occurs primarily with poor sanitary conditions. The virus is believed to enter the body
through the mouth with primary multiplication occurring in the lymphoid tissues in the throat, where it can
persist for about one week. During this time, it is
absorbed into the blood and lymphatics from the gastrointestinal tract where it can reside and multiply,
sometimes for as long as 17 weeks. Once absorbed, it
is widely distributed throughout the body until it ultimately reaches the CNS (the brain and spinal cord).
The infection is passed on to others when poor handwashing allows the virus to remain on the hands after
eating or using the bathroom. Transmission remains
possible while the virus is being excreted and it can be
transmitted for as long as the virus remains in the
throat or feces. The incubation period ranges from
three to 21 days, but cases are most infectious from
seven to 10 days before and after the onset of
symptoms.
GALE ENCYCLOPEDIA OF MEDICINE

Polio

D R . J O N A S E . S A L K (1914–1995)
influenza vaccines, a project that continued until 1949.
That year, as a research professor, Salk began a three-year
project sponsored by the National Foundation for Infantile
Paralysis, also known as the March of Dimes. Caused by
the poliomyelitis virus, polio was also known as infantile
paralysis. Periodic outbreaks of the disease, which attacks
the nervous system, caused death or a lifetime of paralysis,
especially in children. It was a difficult disease to study
because sufficient viruses could not be obtained. Unlike
bacteria, which can be grown in cultures, viruses need
living tissue on which to grow. Once a method for preparing viruses was discovered and improved, sufficient
viruses became available for research.

(Library of Congress.)

Jonas Salk was born in New York, New York, on
October 28, 1914. He received his medical degree from
New York University in 1939. In 1942, Salk began working
for a former teacher, Thomas Francis, Jr., to produce

There are two basic patterns to the virus: the
minor illness (abortive type) and the major illness
(which may be paralytic or nonparalytic). The minor
illness accounts for 80–90% of clinical infections and
is found mostly in young children. It is mild and does
not involve the CNS. Symptoms include a slight fever,
fatigue, headache, sore throat, and vomiting, which
generally develop three to five days after exposure.
Recovery from the minor illness occurs within 24–72
hours. Symptoms of the major illness usually appear
without a previous minor illness and generally affect
older children and adults.
About 10% of people infected with poliovirus
develop severe headache and pain and stiffness of the
neck and back. This is due to an inflammation of the
meninges (tissues which cover the spinal cord and brain).
This syndrome is called ‘‘aseptic meningitis.’’ The term
‘‘aseptic’’ is used to differentiate this type of meningitis
from those caused by bacteria. The patient usually
recovers completely from this illness within several days.
About 1% of people infected with poliovirus
develop the most severe form. Some of these patients
GALE ENCYCLOPEDIA OF MEDICINE

Salk first set out to confirm that there were three virus
types responsible for polio and then began to experiment
with ways to kill the virus and yet retain its ability to
produce an immune response. By 1952, he had produced
a dead virus vaccine that worked against the three virus
types. He began testing. First the vaccine was tested on
monkeys, then on children who had recovered from the
disease, and finally on Salk’s own family and children,
none of whom had ever had the disease. Following largescale trials in 1954, the vaccine was finally released for
public use in 1955. The Salk vaccine was not the first
vaccine against polio, but it was the first to be found safe
and effective. By 1961, there was a 96 percent reduction in
polio cases in the United States.

may have two to three symptom-free days between the
minor illness and the major illness but the symptoms
often appear without any previous minor illness.
Symptoms again include headache and back and
neck pain. The major symptoms, however, are due to
invasion of the motor nerves, which are responsible for
movement of the muscles. This viral invasion causes
inflammation, and then destruction of these nerves.
The muscles, therefore, no longer receive any messages
from the brain or spinal cord. The muscles become
weak, floppy, and then totally paralyzed. All muscle
tone is lost in the affected limb and the muscle becomes
soft (flaccid). Within a few days, the muscle will begin
to decrease in size (atrophy). The affected muscles may
be on both sides of the body (symmetric paralysis), but
are often on unbalanced parts of the body (asymmetric
paralysis). Sensation or the ability to feel is not
affected in these paralyzed limbs.
When poliovirus invades the brainstem (the stalk
of brain which connects the two cerebral hemispheres
with the spinal cord, called bulbar polio), a person
may begin to have trouble breathing and swallowing.
2959

Polio

clinically from aseptic meningitis due to other agents.
Virus isolated from a throat swab and/or feces or
blood tests demonstrating the rise in a specific antibody is required to confirm the diagnosis.

Treatment
There is no specific treatment for polio except
symptomatic. Therapy is designed to make the patient
more comfortable (pain medications and hot packs to
soothe the muscles), and intervention if the muscles
responsible for breathing fail (for instance, a ventilator
to take over the work of breathing). During active
infection, rest on a firm bed is indicated. Physical
therapy is the most important part of management of
paralytic polio during recovery.

Prognosis

In its most severe form, polio causes paralysis of the muscles
of the legs, arms, and respiratory system. All muscle tone is
lost in the affected limb, and the muscle becomes flaccid and
begins to atrophy, as shown in the illustration above.
(Illustration by Electronic Illustrators Group.)

If the brainstem is severely affected, the brain’s control
of such vital functions as heart rate and blood pressure
may be disturbed. This can lead to death.
The maximum state of paralysis is usually reached
within just a few days. The remaining, unaffected
nerves then begin the process of attempting to grow
branches which can compensate for the destroyed
nerves. Fortunately, the nerve cells are not always
completely destroyed. By the end of a month, the
nerve impulses start to return to the apparently paralyzed muscle and by the end of six months, recovery is
almost complete. If the nerve cells are completely
destroyed, however, paralysis is permanent.

Diagnosis
Fever and asymmetric flaccid paralysis without
sensory loss in a child or young adult almost always
indicate poliomyelitis. Using a long, thin needle
inserted into the lower back to withdraw spinal fluid
(lumbar puncture) will reveal increased white blood
cells and no bacteria (aseptic meningitis).
Nonparalytic poliomyelitis cannot be distinguished
2960

When poliovirus causes only the minor illness or
simple aseptic meningitis, the patient can be expected
to recover completely. When the patientis diagnosed
with the major illness, about 50% will recover completely. About 25% of such patients will have slight
disability, and about 25% will have permanent and
serious disability. Approximately 1% of all patients
with major illness die. The greatest return of muscle
function occurs in the first six months, but improvements may continue for two years.
A recently described phenomenon called postpolio syndrome may begin many years after the initial
illness. This syndrome is characterized by a very slow,
gradual decrease in muscle strength.

Prevention
There are two types of polio immunizations available in the United States. Both of these vaccines take
advantage of the fact that infection with polio leads to
an immune reaction, which will give the person permanent, lifelong immunity from re-infection with the
form of poliovirus for which the person was
vaccinated.
The Sabin vaccine (also called the oral polio vaccine or OPV) is given to infants by mouth at the same
intervals as the DPT (three doses). It contains the live,
but weakened, poliovirus, which make the recipient
immune to future infections with poliovirus. Because
OPV uses live virus, it has the potential to cause infection in individuals with weak immune defenses (both
in the person who receives the vaccine and in close
contacts). This is a rare complication, however, occurring in only one in 6.8 million doses administered and
GALE ENCYCLOPEDIA OF MEDICINE

Aseptic—Sterile; containing no microorganisms,
especially no bacteria.
Asymmetric—Not occurring evenly on both sides
of the body.
Atrophy—Shrinking; growing smaller in size.
Brainstem—The stalk of the brain which connects
the two cerebral hemispheres with the spinal cord.
DPT—Diphtheria, Pertussis and Tetanus injections.
Epidemic—Refers to a situation in which a particular disease rapidly spreads among many people in
the same geographical region over a small time
period.
Flaccid—Weak, soft, floppy.
Gastrointestinal—Pertaining to the stomach and
intestines.
Lymph/lymphatic—One of the three body fluids
that is transparent and a slightly yellow liquid that
is collected from the capillary walls into the tissues
and circulates back to the blood supply.
Paralysis—The inability to voluntarily move.
Symmetric—Occurring on both sides of the body,
in a mirror-image fashion.

one in every 6.4 million doses from having close contact with someone who received the vaccine.
The Salk vaccine (also called the killed polio
vaccine or inactivated polio vaccine) consists of a
series of three shots that are given just under the
skin. This immunization contains no live virus, just
the components of the virus that provoke the recipient’s immune system to react as if the recipient were
actually infected with the poliovirus. The recipient
thus becomes immune to infection with the poliovirus
in the future.
In the 13 years following the launching of the
Global Polio Eradication Initiative, the number of
cases has fallen 99% from an estimated 350,000 cases
to less than 3,500 cases worldwide in 2000. At the end
of 2000, the number of polio-infected countries was
approximately 20, down from 125. The goal of the
World Health Organization (WHO) is to have polio
eliminated from the planet by the year 2005. The virus
has still been identified in Africa and parts of Asia, so
travelers to those areas may want to check with their
physicians concerning booster vaccinations.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Braunwald MD, E., A. Fauci MD, D. Kasper MD, S.
Hauser MD,D. Longo MD, and J. Jameson MD.
Harrison’s Principles of Internal Medicine. NewYork:
McGraw-Hill, 2001.
Cecil, R., and L. Goldman. Cecil Textbook ofMedicine.
Philadelphia: W.B. Saunders, 1999.
PERIODICALS

Centers for Disease Control and Prevention. ‘‘Poliomyelitis
prevention in the United States: Updated recommendations of the AdvisoryCommittee on Immunization
Practices (ACIP).’’ MMWR 2000. <http://
www.cdc.gov/>.
OTHER

World Health Organization. ‘‘Global Polio
EradicationProgress 2000.’’ <http://www.polioeradication.org/>.

Linda K. Bennington, CNS

Poliomyelitis see Polio
Polyangiitis overlap syndrome see Vasculitis
Polyarteritis nodosa see Vasculitis

Polycystic kidney disease
Definition
Polycystic kidney disease (PKD) is one of the most
common of all life-threatening human genetic disorders. It is an incurable genetic disorder characterized
by the formation of fluid-filled cysts in the kidneys of
affected individuals. These cysts multiply over time. It
was originally believed that the cysts eventually caused
kidney failure by crowding out the healthy kidney
tissue. It is now thought that the kidney damage seen
in PKD is actually the result of the body’s immune
system. The immune system, in its attempts to rid the
kidney of the cysts, instead progressively destroys the
formerly healthy kidney tissue.

Description
A healthy kidney is about the same size as a
human fist. PKD cysts, which can be as small as the
head of a pin or as large as a grapefruit, can expand the
kidneys until each one is bigger than a football and
weighs as much as 38lb (17 kg).
2961

Polycystic kidney disease

Resources

KEY TERMS

Polycystic kidney disease

There are two types of PKD: infantile PKD,
which generally shows symptoms prior to birth; and
adult onset PKD. Individuals affected with infantile
PKD are often stillborn. Among the liveborn individuals affected with infantile PKD, very few of these
children survive to the age of two. The adult onset
form of PKD is much more common. The time and
degree of symptom onset in the adult form of PKD can
vary widely, even within a single family with two or
more affected individuals. Symptoms of this form of
PKD usually start to appear between the ages of 20
and 50. Organ deterioration progresses more slowly in
adult onset PKD than it does in the infantile form; but,
if left untreated, adult onset PKD also eventually leads
to kidney failure.
One of the most common of all life-threatening
genetic diseases, PKD affects more than 60,000
Americans. Over 12.5 million people worldwide are
affected with PKD. Approximately one in every 400
to 1,000 people is affected with ADPKD. Another one
in 10,000 affected with ARPKD. PKD is observed in
equal numbers in both males and females. PKD is also
observed with equal frequency among ethnic groups.

Causes and symptoms
Polycystic kidney disease is expressed as both a
recessive and a dominant trait. A recessive genetic trait
will not cause disease in a child unless it it inheritied
from both parents. A dominant genetic trait can be
inherited from just one parent. Those people affected
with autosomal dominant PKD (ADPKD) have the
much more common adult onset form. Those with
autosomal recessive PKD (ARPKD) have the infantile form.
There are mutations on at least three genes that
cause adult onset PKD. Approximately 85% of these
cases are known to arise from mutations in the PKD1
gene that has been mapped to a region on the short
arm of chromosome 16 (16p13.3-p13.12). Another 10–
15% of cases of adult onset PKD are thought to be
caused by mutations in the PKD2 gene that has been
mapped to a region on the long arm of chromosome 4
(4q21-q23). As of early 2001, it is thought that the
remainder of the cases of PKD are caused by mutations in the PKD3 gene, which has not yet been
mapped. This unidentified ‘‘PKD3 gene’’ may, in
fact, be more than one gene.
Adult onset PKD is transmitted from parents to
their offspring as a non-sex linked (autosomal) dominant trait. This means that if either parent carries this
genetic mutation, there is a 50% chance that their
child will inherit this disease. In the case of two
2962

affected parents, there is a 75% probability that their
children will be affected with adult onset PKD.
Infantile PKD is caused by a non-sex linked (autosomal) recessive genetic mutation that has been
mapped to a region on the short arm of chromosome
6 (6p21). Both parents must be carriers of this mutation for their children to be affected with infantile
PKD. In the case of two carrier parents, the probability is 25% that their child will be affected by infantile
PKD.
A baby born with infantile PKD has floppy, lowset ears, a pointed nose, a small chin, and folds of skin
surrounding the eyes (epicanthal folds). Large, rigid
masses can be felt on the back of both thighs (flanks),
and the baby usually has trouble breathing.
In the early stages of adult onset PKD, many
people show no symptoms. Generally, the first symptoms to develop are: high blood pressure (hypertension); general fatigue; pain in the lower back or the
backs of the thighs; headaches; and/or urinary tract
infections accompanied by frequent urination.
As PKD becomes more advanced, the kidneys’
inability to function properly becomes more pronounced. The cysts on the kidney may begin to rupture
and the kidneys tend to be much larger than normal.
Individuals affected with PKD have a much higher
rate of kidney stones than the rest of the population
at this, and later stages, of the disease. Approximately
60% of those individuals affected with PKD develop
cysts in the liver, while 10% develop cysts in the
pancreas.
Because the kidneys are primarily responsible for
cleaning the blood, individuals affected with PKD
often have problems involving the circulatory system.
These include: an underproduction of red blood cells
which results in an insufficient supply of oxygen to the
tissues and organs (anemia); an enlarged heart (cardiac hypertrophy) probably caused by long term
hypertension; and, a leakage of the valve between the
left chambers (auricle and ventricle) of the heart
(mitral valve prolapse). Less common (affecting
approximately 5% of PKD patients) are brain aneurysms. An aneurysm is an abnormal and localized bulging of the wall of a blood vessel. If an aneurysm
within the brain leaks or bursts, it may cause a stroke
or even death.
Other health problems associated with adult onset
PKD include: chronic leg or back pain; frequent infections; and herniations of the groin and abdomen,
including herniation of the colon (diverticular disease). A herniation, or hernia, is caused when a tissue,
designed to hold the shape of an underlying tissue,
GALE ENCYCLOPEDIA OF MEDICINE

Treatment

A pair of human kidneys. Tthe left a polycystic kidney, the
right a normal kidney. (Photograph by A. Glauberman, Photo
Researchers, Inc. Reproduced by permission.)

becomes weakened at a particular spot. The underlying tissue pushes against this weakened area until the
area is no longer able to hold back the underlying
tissue and the area forms an abnormal bulge through
which the underlying tissue projects. Diverticular disease is caused by a weakening of the muscles that hold
the shape of the organs of the digestive tract. These
muscles weaken allowing these organs, particularly
one section of the colon, to form sac-like projections
that can trap feces and become infected, or rupture.
In the final stages of PKD, the major symptom is
kidney (renal) failure. Renal failure is indicated by an
increase of nitrogen (in the form of urea) in the blood
(uremia, or uremic poisoning). Uremia is a rapidly fatal
condition without treatment.

Diagnosis
Many patients who have PKD do not have any
symptoms. Their condition may not be discovered
unless tests that detect it are performed for other
reasons.
When symptoms of PKD are present, the diagnostic procedure begins with a family medical history
and physical examination of the patient. If several
family members have PKD, there is a strong likelihood that the patient has it too. If the disease is
advanced, the doctor will be able to feel the patient’s
enlarged kidneys. Heart murmur, high blood pressure,
and other signs of cardiac impairment can also be
detected.
Urinalysis and a blood test called creatine clearance can indicate how effectively the kidneys are functioning. Scanning procedures using intravenous dye
reveal kidney enlargement or deformity and scarring
GALE ENCYCLOPEDIA OF MEDICINE

There is no way to prevent cysts from forming or
becoming enlarged, or to prevent PKD from progressing to kidney failure. Treatment goals include preserving healthy kidney tissue; controlling symptoms and,
preventing infection and other complications.
If adult PKD is diagnosed before symptoms
become evident, urinalysis and other diagnostic tests
are performed at six-week intervals to monitor the
patient’s health status. If results indicate the presence
of infection or another PKD-related health problem,
aggressive antibiotic therapy is initiated to prevent
inflammation that can accelerate disease progression;
iron supplements or infusion of red blood cells are
used to treat anemia; and surgery may be needed to
drain cysts that bleed, cause pain, have become
infected, or interfere with normal kidney function.
Lowering high blood pressure can slow loss of
kidney function. Blood-pressure control, which is the
cornerstone of PKD treatment, is difficult to achieve.
Therapy may include antihypertensive medications,
diuretic medications, and/or a low-salt diet. As kidney
function declines, some patients need dialysis and/or a
kidney transplant.
There is no known way to prevent PKD, but
certain lifestyle modifications can help control symptoms. People who have PKD should not drink heavily
or smoke. They should not use aspirin, non-steroidal
anti-inflammatory drugs (NSAIDs), or other prescription or over-the-counter medications that can impair
kidney function. Individuals affected with PKD
should eat a balanced diet, exercise regularly, and
maintain a weight appropriate for their height, age,
and body type. Regular medical monitoring is also
recommended.

Prognosis
There is no known cure for PKD. Those affected
with infantile PKD generally die before the age of two.
In adults, untreated disease can be rapidly fatal or
continue to progress slowly, even after symptoms of
kidney failure appear. About half of all adults with
PKD also develop kidney failure. Unless the patient
undergoes dialysis or has a kidney transplant, this
2963

Polycystic kidney disease

caused by cysts. Ultrasound and computed tomography scans (CT scans) can reveal kidney enlargement
and the cysts that caused it. CT scans can highlight
cyst-damaged areas of the kidneys. A sampling of the
kidney cells (biopsy) may be performed to verify the
diagnosis.

Polycystic ovary syndrome

Resources

KEY TERMS
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Cancer—A disease caused by uncontrolled growth
of the body’s cells.
Computed tomography (CT) scan—An imaging
procedure that produces a three-dimensional picture of organs or structures inside the body, such as
the brain.
Cyst—An abnormal sac or closed cavity filled with
liquid or semisolid matter.
Diuretics—Medications that increase the excretion
of urine.
Kidney—Either of two organs in the lumbar region
that filter the blood, excreting the end products of
the body’s metabolism in the form of urine and
regulating the concentrations of hydrogen, sodium,
potassium, phosphate and other ions in the body.
Magnetic resonance imaging (MRI)—A technique
that employs magnetic fields and radio waves to
create detailed images of internal body structures
and organs, including the brain.
Ultrasonogram—A procedure where high-frequency
sound waves that cannot be heard by human ears
are bounced off internal organs and tissues. These
sound waves produce a pattern of echoes, which are
then used by the computer to create sonograms or
pictures of areas inside the body.
Uremic poisoning—Accumulation of waste products in the body.

PERIODICALS

Koptides, M., and C. Deltas. ‘‘Autosomal dominant polycystic kidney disease: Molecular genetics and molecular
pathogenesis.’’ Human Genetics August 2000: 115–26.
Pei, Y., A. Paterson, K. Wang, N. He, et al. ‘‘Bilineal disease
and trans-heterozygotes in autosmal dominant polycystic kidney disease.’’ American Journal of Human
Genetics February 2001: 355–63.
ORGANIZATIONS

Polycystic Kidney Disease Foundation. 4901 Main Street,
Kansas City, MO 64112-2634. (800) PKD-CURE.
<http://www.pkdcure.org/home.htm>.
OTHER

Brochert, Adam, MD. ‘‘Polycystic Kidney Disease.’’
September 4, 2000. HealthAnswers. <http://
www.healthanswers.com/library/library_fset.asp>.
Cooper, Joel R. ‘‘Treating Polycystic Kidney Disease. What
Does the Future Hold?’’ Coolware, Inc. <http://
www.coolware.com/health/medical_reporter/
kidney1.html>.
Online Mendelian Inheritance in Man (OMIM). February
15, 2001. <http://www.ncbi.nlm.nih.gov/htbin-post/
Omim/dispmim?600595>.
Polycystic Kidney Disease Access Center. <http://
www.nhpress.com/pkd/>.

Paul A. Johnson, Ed.M.

Polycystic ovary syndrome
Definition

condition usually leads to death within four years of
diagnosis.
Although medical treatment can temporarily alleviate symptoms of PKD, the expanding cysts continue
to increase pressure on the kidneys. Kidney failure and
uremic poisoning (accumulation of waste products the
body is unable to eliminate) generally cause death
about 10 years after symptoms first appear.
Medications used to fight cancer and reduce elevated cholesterol levels have slowed the advance of
PKD in laboratory animals. They may soon be used
to treat adults and children who have the disease.
Researchers are also evaluating the potential benefits
of anti-inflammatory drugs, which may prevent the
scarring that destroys kidney function.
2964

Polycystic ovary syndrome (PCOS) is a condition
characterized by the accumulation of numerous cysts
(fluid-filled sacs) on the ovaries associated with high
male hormone levels, chronic anovulation (absent
ovulation), and other metabolic disturbances. Classic
symptoms include excess facial and body hair, acne,
obesity, irregular menstrual cycles, and infertility.

Description
PCOS, also called Stein-Leventhal syndrome, is a
group of symptoms caused by underlying hormonal
and metabolic disturbances that affect about 6% of
premenopausal women. PCOS symptoms appear as
early as adolescence in the form of amenorrhea (missed
periods), obesity, and hirsutism, the abnormal growth
of body hair.
GALE ENCYCLOPEDIA OF MEDICINE

One of the most important characteristics of
PCOS is hyperandrogenism, the excessive production
of male hormones (androgens), particularly testosterone, by the ovaries. This accounts for the male hairgrowth patterns and acne in women with PCOS.
Hyperandrogenism has been linked with insulin resistance (the inability of the body to respond to insulin)
and hyperinsulinemia (high blood insulin levels), both
of which are common in PCOS.

Causes and symptoms
While the exact cause of PCOS is unknown, it runs
in families, so the tendency to develop the syndrome
may be inherited. The interaction of hyperinsulinemia
and hyperandrogenism is believed to play a role in
chronic anovulation in susceptible women.
The numbers and types of PCOS symptoms that
appear vary among women. These include:


Hirsutism. Related to hyperandrogenism, this occurs
in 70% of women.



Obesity. Approximately 40–70% of persons with
PCOS are overweight.



Anovulation
and
menstrual
disturbances.
Anovulation appears as amenorrhea in 50% of
women, and as heavy uterine bleeding in 30% of
women. However, 20% of women with PCOS have
normal menstruation.



Male-pattern hair loss. Some women with PCOS
develop bald spots.



Infertility. Achieving pregnancy is difficult for many
women with PCOS.



Polycystic ovaries. Most, but not all, women with
PCOS have multiple cysts on their ovaries.



Skin discoloration. Some women with PCOS have
dark patches on their skin.



Abnormal blood chemistry. Women with PCOS have
high levels of low-density lipoprotein (LDL or ‘‘bad’’)
cholesterol and triglycerides, and low levels of highdensity lipoprotein (HDL or ‘‘good’’) cholesterol.



Hyperinsulinemia. Some women with PCOS have
high blood insulin levels, particularly if they are
overweight.

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
PCOS is diagnosed when a woman visits her doctor for treatment of symptoms such as hirsutism, obesity, menstrual irregularities, or infertility. Women
with PCOS are treated by a gynecologist, a doctor
who treats diseases of the female reproductive organs,
or a reproductive endocrinologist, a specialist who
treats diseases of the body’s endocrine (hormones
and glands) system and infertility.
PCOS can be difficult to diagnose because its
symptoms are similar to those of many other diseases
or conditions, and because all of its symptoms may not
occur. A doctor takes a complete medical history,
including questions about menstruation and reproduction, and weight gain. Physical examination
includes a pelvic examination to determine the size of
the ovaries, and visual inspection of the skin for hirsutism, acne, or other changes. Blood tests are performed to measure levels of luteinizing hormone,
follicle stimulating hormone, estrogens, androgens,
glucose, and insulin. A glucose-tolerance test may be
administered. An ultrasound examination of the ovaries is performed to evaluate their size and shape. Most
insurance plans cover the costs of diagnosing and
treating PCOS and its related problems.

Treatment
PCOS treatment is aimed at correcting anovulation, restoring normal menstrual periods, improving
fertility, eliminating hirsutism and acne, and preventing future complications related to high insulin and
blood lipid (fat) levels. Treatment consists of weight
loss, drugs or surgery, and hair removal, depending
upon which symptoms are most bothersome, and
whether a woman desires pregnancy.
Weight loss
In overweight women, weight loss (as little as 5%)
through diet and exercise may correct hyperandrogenism, and restore normal ovulation and fertility. This is
often tried first.
Drugs
HORMONAL DRUGS. Women who do not want to
become pregnant and require contraception (spontaneous ovulation occurs occasionally among women
with PCOS) are treated with low-dose oral contraceptive pills (OCPs). OCPs bring on regular menstrual
periods and correct heavy uterine bleeding, as well as
hirsutism, although improvement may not be seen for
up to a year.

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Polycystic ovary syndrome

A disturbance in normal hormonal signals prevents ovulation in women with PCOS. Throughout
the cycle, estrogen levels remain steady, luteinizing
hormone (LH) levels are high, and follide stimulating
hormone (FSH) and progesterone levels are low. Since
eggs are rarely or never released from their follicles,
multiple ovarian cysts develop over time.

Polycystic ovary syndrome

If an infertile woman desires to become pregnant,
the first drug usually given to help induce ovulation is
clomiphene citrate (Clomid), which results in pregnancy in about 70% of women but can cause multiple
births. In the 20–25% of women who do not respond
to clomiphene, other drugs that stimulate follicle
development and induce ovulation, such as human
menstrual gonadotropin (Pergonal) and human chorionic gonadotropin (HCG), are given. However, these
drugs have a lower pregnancy rate (less than 30%), a
higher rate of multiple pregnancy (from 5–30%,
depending on the dose of the drug), and a higher risk
of medical problems. Women with PCOS have a high
rate of miscarriage (30%), and may be treated with the
gonadotropin-releasing hormone agonist leuprolide
(Lupron) to reduce this risk.
Since women with PCOS do not have regular
endometrial shedding due to high estrogen levels,
they are at increased risk for overgrowth of this tissue
and endometrial cancer. The drug medroxyprogesterone acetate, when taken for the first 10 days of each
month, causes regular shedding of the endometrium,
and reduces the risk of cancer. However, in most cases,
oral contraceptive pills are used instead to bring about
regular menstruation.
OTHER DRUGS. Another drug that helps to trigger
ovulation is the steroid hormone dexamethasone. This
drug acts by reducing the production of androgens by
the adrenal glands.

The antiandrogen spironolactone (Aldactazide),
which is usually given with an oral contraceptive,
improves hirsutism and male-pattern baldness by
reducing androgen production, but has no effect on
fertility. The drug causes abnormal uterine bleeding
and is linked with birth defects if taken during pregnancy. Another antiandrogen used to treat hirsutism,
flutamide (Eulexin), can cause liver abnormalities,
fatigue, mood swings, and loss of sexual desire. A
drug used to reduce insulin levels, metformin
(Glucophage), has shown promising results in
women with PCOS hirsutism, but its effects on infertility and other PCOS symptoms are unknown. Drug
treatment of hirsutism is long-term, and improvement
may not be seen for up to a year or longer.
Acne is treated with antibiotics, antiandrogens,
and other drugs such as retinoic acids (vitamin A
compounds).
Surgical treatment
Surgical treatment of PCOS may be performed if
drug treatment fails, but it is not common. A wedge
resection, the surgical removal of part of the ovary and
2966

cysts through a laparoscope (an instrument inserted
into the pelvis through a small incision), or an abdominal incision, reduces androgen production and
restores ovulation. Although laparoscopic surgery is
less likely to cause scar tissue formation than abdominal surgery, both are associated with the potential
for scarring that may require additional surgery.
Laparoscopic ovarian drilling is another type of
laparoscopic surgery used to treat PCOS. The ovarian
cysts are penetrated with a laser beam and some of the
fluid is drained off. Between 50–65% of women may
become pregnant after either type of surgery.
Some cases of severe hirsutism are treated by
removal of the uterus (hysterectomy) and the ovaries
(oopherectomy), followed by estrogen replacement
therapy.
Other treatment
Hirsutism may be treated by hair removal techniques such as shaving, depilatories (chemicals that
break down the structure of the hair), tweezing, waxing, electrolysis (destruction of the hair root by an
electrical current), or the destruction of hair follicles
by laser therapy. However, the treatments may have to
be repeated.

Alternative treatment
PCOS can be addressed using many types of alternative treatment. The rebalancing of hormones is a
primary focus of all these therapies. Acupuncture
works on the body’s energy flow according to the
meridian system. Chinese herbs, such as gui zhi fu
ling wan, can be effective. In naturopathic medicine,
treatment focuses on helping the liver function more
optimally in the horomonal balancing process.
Dietary changes, including reducing animal products
and fats, while increasing foods that nourish the liver
such as carrots, dark green vegetables, lemons, and
beets, can be beneficial. Essential fatty acids, including
flax oil, evening primrose oil (Oenothera biennis), and
black currant oil, act as anti-inflammatories and hormonal regulators. Western herbal medicine uses phytoestrogen and phytoprogesteronic herbs, such as blue
cohosh (Caulophyllum thalictroides) and false unicorn
root (Chamaelirium luteum), as well as liver herbs, like
dandelion (Taraxacum mongolicum), to work toward
hormonal balance. Supplementation with antioxidants, including zinc, and vitamins A, E, and C, is
also recommended. Constitutional homeopathy can
bring about a deep level of healing with the correct
remedies.
GALE ENCYCLOPEDIA OF MEDICINE

Androgens—Male sex hormones produced by
the adrenal glands and testes, the male sex
glands.
Anovulation—The absence of ovulation.
Antiandrogens—Drugs that inhibit androgen
production.
Estrogens—Hormones produced by the ovaries,
the female sex glands.
Follicle stimulating hormone—A hormone that stimulates the growth and maturation of mature eggs
in the ovary.
Gynecologist—A physician with specialized training in diseases and conditions of the female reproductive system.
Hirsutism—An abnormal growth of hair on the face
and other parts of the body caused by an excess of
androgens.
Hyperandrogenism—The excessive secretion of
androgens.
Hyperinsulinemia—High blood insulin levels.
Insulin resistance—An inability to respond to insulin, a hormone produced by the pancreas that helps
the body to use glucose.
Laparoscope—An instrument inserted into the
pelvis through a small incision.
Luteinizing hormone—A hormone that stimulates
the secretion of sex hormones by the ovary.
Ovarian follicles—Structures found within the
ovary that produce eggs.

Prognosis
With proper diagnosis and treatment, most
PCOS symptoms can be adequately controlled or
eliminated. Infertility can be corrected and pregnancy achieved in most women although, in some,
hormonal disturbances and anovulation may recur.
Women should be monitored for endometrial cancer.
Because of the high rate of hyperinsulinemia seen in
PCOS, women with the disorder should have their
glucose levels checked regularly to watch for the
development of diabetes. Blood pressure and cholesterol screening are also needed because these women
also tend to have high levels of LDL cholesterol and
triglycerides, which put them at risk for developing
heart disease.
GALE ENCYCLOPEDIA OF MEDICINE

There is no known way to prevent PCOS, but if
diagnosed and treated early, risks for complications
such as and heart disease and diabetes may be minimized. Weight control through diet and exercise stabilizes hormones and lowers insulin levels.
Resources
BOOKS

DeGroot, Leslie J., and J. Larry Jameson. Endocribnology.
4th ed. Philadelphia: W B Saunders, 2001.
Genazzani, A. R., and F. Petraglia. Advances in
Gynecological Endocrinology. London: Parthenon
Press, 2001.
Nader, Shala. Case Studies in Reproductive Endocrinology.
London: Edward Arnold, 2000.
Speroff, Leon. Handbook for Clinical Gynecologic
Endocrinology and Infertility Philadelphia: Lippincott
Williams & Wilkins, 2001.
Spratt, Daniel, and Nanette Santoro. Endocrinology and
Management of Reproduction and Fertility: Practical
Diagnosis and Treatment. Totowa, NJ: Humana Press,
2001.
PERIODICALS

Bracero, N., H. A. Zacur. ‘‘Polycystic ovary syndrome and
hyperprolactinemia.’’ Obstetrics and Gynecology Clinics
of North America 28, no. 1 (2001): 77-84.
Calvo, R.M., et al. ‘‘Role of the follistatin gene in women
with polycystic ovary syndrome.’’ Fertility and Sterility
75, no. 5 (2001): 1020-102.
Dejager, S., et al. ‘‘Smaller LDL particle size in women with
polycystic ovary syndrome compared to controls.’’
Clinical Endocrinology (Oxford) 54, no. 4 (2001): 455–
462.
Heinonen, S., et al. ‘‘Apolipoprotein E alleles in women with
polycystic ovary syndrome.’’ Fertility and Sterility 75,
no. 5 (2001): 878-880.
Hoeger, K. ‘‘Obesity and weight loss in polycystic ovary
syndrome.’’ Obstetrics and Gynecology Clinics of North
America 28, no. 1 (2001): 85-97.
Iuorno, M. J., and J. E. Nestler. ‘‘Insulin-lowering drugs in
polycystic ovary syndrome.’’ Obstetrics and Gynecology
Clinics of North America 28, no. 1 (2001): 153-164.
Kalro, B. N., T. L. Loucks, and S. L. Berga.
‘‘Neuromodulation in polycystic ovary syndrome.’’
Obstetrics and Gynecology Clinics of North America 28,
no. 1 (2001): 35-62.
Legro, R. S. ‘‘Diabetes prevalence and risk factors in polycystic ovary syndrome.’’ Obstetrics and Gynecology
Clinics of North America 28, no. 1 (2001): 99-109.
Lewis, V. ‘‘Polycystic ovary syndrome. A diagnostic challenge.’’ Obstetrics and Gynecology Clinics of North
America 28, no. 1: 1-20.
Moran, C., and R. Azziz. ‘‘The role of the adrenal cortex in
polycystic ovary syndrome.’’ Obstetrics and Gynecology
Clinics of North America 28, no. 1 (2001): 63-75.
2967

Polycystic ovary syndrome

Prevention

KEY TERMS

Polycythemia vera

Padmanabhan, V., et al. ‘‘Dynamics of bioactive folliclestimulating hormone secretion in women with polycystic ovary syndrome: effects of estradiol and progesterone.’’ Fertility and Sterility 75, no. 5 (2001): 881-888.
Phipps, W. R. ‘‘Polycystic ovary syndrome and ovulation
induction.’’ Obstetrics and Gynecology Clinics of North
America 28, no. 1 (2001): 165-182.
Talbott, E. O., et al. ‘‘Cardiovascular risk in women with
polycystic ovary syndrome.’’ Obstetrics and Gynecology
Clinics of North America 28, no. 1 (2001): 111-133.
Zacur, H. A. ‘‘Polycystic ovary syndrome, hyperandrogenism, and insulin resistance.’’ Obstetrics and Gynecology
Clinics of North America 28, no. 1 (2001): 21-33.
Zborowski, J. V., et al. ‘‘Polycystic ovary syndrome, androgen excess, and the impact on bone.’’ Obstetrics and
Gynecology Clinics of North America 28, no. 1 (2001):
135–151.
ORGANIZATIONS

American Academy of Family Physicians. 11400 Tomahawk
Creek Parkway, Leawood, KS 66211-2672. (913) 9066000. <http://www.aafp.org/>. fp@aafp.org.
American Medical Association. 515 N. State Street,
Chicago, IL 60610. (312) 464-5000. <http://www.amaassn.org/>.
Polycystic Ovarian Syndrome Association. PO Box 80517,
Portlabd, OR 97280. (877) 775-7267. <http://
www.pcosupport.org/>. info@pcossupport.org.

(RBCs), white blood cells (WBCs), and platelets. PV is
called a myeloproliferative disorder, which means that
the bone marrow is producing too many cells too
quickly. Most of the symptoms of PV are related to
the increased volume of the patient’s blood and its
greater thickness (high viscosity). PV sometimes
evolves into a different myeloproliferative disorder
or into acute leukemia.

Description
Polycythemia vera is a relatively common progressive disorder that develops over a course of
10–20 years. In the United States, PV affects about
one person in every 200,000. PV has several other
names, including splenomegalic polycythemia,
Vaquez-Osler syndrome, erythremia, and primary
polycythemia. Primary polycythemia means that the
disorder is not caused or triggered by other illnesses.
PV most commonly affects middle-aged adults. It is
rarely seen in children or young adults and does not
appear to run in families. The male/female ratio is 2:1.
Risk factors for polycythemia vera include:


Caucasian race



male sex



age between 40 and 60

OTHER

American Academy of Family Physicians. <http://
www.aafp.org/afp/20000901/1079.html>.
Jewish Hospital of Cincinnati. <http://uc.edu/~gartsips/
polycyst.htm>.
Merck Manual. <http://www.merck.com/pubs/mmanual/
section18/chapter235/235d.htm>.
Vanderbilt University School of Medicine. <http://
www.mc.vanderbilt.edu/peds/pidl/adolesc/
polcysov.htm>.
Women’s Health-UK. <http://www.womens-health.co.uk/
pcos.htm>.

L. Fleming Fallon, Jr., MD, DrPH

Polycythemia see Secondary polycythemia
Polycythemia rubra vera see Polycythemia
vera

Polycythemia vera
Definition
Polycythemia vera (PV) is a chronic blood disorder marked by an abnormal increase in three types of
blood cells produced by bone marrow: red blood cells
2968

Causes and symptoms
The cause of PV remains uncertain. In general, the
increased mass of red blood cells in the patient’s blood
causes both hemorrhage and abnormal formation of
blood clots in the circulatory system (thrombosis). The
reasons for these changes in clotting patterns are not
yet fully understood.
Early symptoms
The symptoms of early PV may be minimal–it is
not unusual for the disorder to be discovered during a
routine blood test. More often, however, patients have
symptoms that include headaches, ringing in the ears,
tiring easily, memory problems, difficulty breathing,
giddiness or lightheadedness, hypertension, visual problems, or tingling or burning sensations in their hands
or feet. Another common symptom is itching (pruritus). Pruritus related to PV is often worse after the
patient takes a warm bath or shower.
Some patients’ early symptoms include unusually
heavy bleeding from minor cuts, nosebleeds, stomach
ulcers, or bone pain. In a few cases, the first symptom
is the development of blood clots in an unusual part of
the circulatory system (e.g., the liver).
GALE ENCYCLOPEDIA OF MEDICINE

As the disease progresses, patients with PV may
have episodes of hemorrhage or thrombosis.
Thrombosis is the most frequent cause of death from
PV. Other complications include a high level of uric
acid in the blood and an increased risk of peptic ulcer
disease. About 10% of PV patients eventually develop
gout; another 10% develop peptic ulcers.
Spent phase
The spent phase is a development in late PV that
affects about 30% of patients. The bone marrow eventually fails and the patient becomes severely anemic,
requiring repeated blood transfusions. The spleen and
liver become greatly enlarged–in the later stages of PV,
the patient’s spleen may fill the entire left side of the
abdomen.

Diagnosis
Physical examination
PV is often a diagnosis of exclusion, which means
that the doctor will first rule out other possible causes
of the patient’s symptoms. The doctor can detect some
signs of the disorder during a physical examination.
Patients with PV will have an enlarged spleen (splenomegaly) in 75% of cases. About 50% will have a
slightly enlarged liver. The doctor can feel these
changes when he or she presses on (palpates) the
patient’s abdomen while the patient is lying flat. An
eye examination will usually reveal swollen veins at the
back of the eye. Patients with PV often have unusually
red complexions; mottled red patches on their legs,
feet, or hands; or swelling at the ends of the fingers.
Diagnostic criteria for PV
Accurate diagnosis of PV is critical because its
treatment may require the use of drugs with the
potential to cause leukemia. The results of the
patient’s blood tests are evaluated according to criteria worked out around 1970 by the Polycythemia
Vera Study Group. The patient is considered to
have PV if all three major criteria are met; or if
the first two major criteria and any two minor
criteria are met.
Major criteria:


red blood cell mass greater than 36 mL/kg in males,
greater than 32 mL/kg in females



arterial oxygen level greater than 92%



splenomegaly

GALE ENCYCLOPEDIA OF MEDICINE






platelet count greater than 400,000/mm3
WBC greater than 12,000/mm3 without fever or
infection
leukocyte alkaline phosphatase (LAP) score greater
than 100 with increased blood serum levels of vitamin B12
Laboratory testing

BLOOD TESTS. The diagnosis of PV depends on a
set of findings from blood tests. The most important
single measurement is the patient’s red blood cell mass
as a proportion of the total blood volume. This measurement is made by tagging RBCs with radioactive
chromium (51Cr) in order to determine the patient’s
RBC volume. While a few patients with PV may have a
red cell mass level within the normal range if they have
had recent heavy bleeding, a high score may eliminate
the need for some other tests. A score higher than 36
mL/kg for males and 32 mL/kg for females on the 51Cr
test suggests PV. Measurements of the oxygen level in
the patient’s arterial blood, of the concentration of
vitamin B12 in the blood serum, and of leukocyte alkaline phosphatase (LAP) staining can be used to distinguish PV from certain types of leukemia or from other
types of polycythemia. LAP staining measures the
intensity of enzyme activity in a type of white blood
cell called a neutrophil. In PV, the LAP score is higher
than normal whereas in leukemia it is below normal.
BONE MARROW TESTS. Bone marrow testing can
be used as part of the diagnostic process. A sample
of marrow can be cultured to see if red blood cell
colonies develop without the addition of a hormone
that stimulates RBC production. The growth of a cell
colony without added hormone indicates PV. Bone
marrow testing is also important in monitoring the
progress of the disease, particularly during the spent
phase.
GENETIC TESTING. Genetic testing can be used to
rule out the possibility of chronic myeloid leukemia.
Patients with this disease have a characteristic chromosomal abnormality called the Philadelphia chromosome. The Philadelphia chromosome does not
occur in patients with PV.

Imaging studies
Imaging studies are not necessary to make the
diagnosis of PV. In some cases, however, imaging
studies can detect enlargement of the spleen that the
doctor may not be able to feel during the physical
examination.
2969

Polycythemia vera

Minor criteria:

Later symptoms and complications

Polycythemia vera

Treatment
Treatment of PV is tailored to the individual
patient according to his or her age, the severity of the
symptoms and complications, and the stage of the
disease.
Phlebotomy
Phlebotomy is the withdrawal of blood from a
vein. It is the first line of treatment for patients with
PV. Phlebotomy is used to bring down the ratio of red
blood cells to fluid volume (the hematocrit) in the
patient’s blood to a level below 45%. In most cases
the doctor will withdraw about 500 mL of blood
(about 15 fluid ounces) once or twice a week until the
hematocrit is low enough. Phlebotomy is considered
the best course of treatment for patients younger than
60 and for women of childbearing age. Its drawback is
that patients remain at some risk for either thrombosis
or hemorrhage.
Myelosuppression
Myelosuppressive therapies are used to slow
down the body’s production of blood cells. They are
given to patients who are older than 60 and at high risk
for thrombosis. These therapies, however, increase the
patient’s risk of developing leukemia. The substances
most frequently used as of 1998 include hydroxyurea
(Hydrea), interferon alfa (Intron), or radioactive
phosphorus (32P). 32P is used only in elderly patients
with life expectancies of less than five years because it
causes leukemia in about 10% of patients. Interferon
alfa is expensive and causes side effects resembling the
symptoms of influenza but is an option for some
younger PV patients.

KEY TERMS
Anagrelide—An orphan drug that is approved for
treating PV patients on an investigational basis.
Anagrelide works by controlling the level of platelets in the blood.
Leukocyte alkaline phosphatase (LAP) test—A
blood test that measures the level of enzyme activity in a type of white blood cell called neutrophils.
Myeloproliferative disorder—A disorder in which
the bone marrow produces too many cells too
rapidly.
Myelosuppressive therapy—Any form of treatment
that is aimed at slowing down the rate of blood cell
production.
Orphan drug—A drug that is known to be useful in
treatment but lacks sufficient funding for further
research and development.
Philadelphia chromosome—An abnormal chromosome that is found in patients with a chronic form of
leukemia but not in PV patients.
Phlebotomy—Drawing blood from a patient’s vein
as part of diagnosis or therapy. Phlebotomy is
sometimes called venesection. It is an important
part of the treatment of PV.
Pruritus—An itching sensation or feeling. In PV the
itching is not confined to a specific part of the body
and is usually worse after a warm bath or shower.
Spent phase—A late development in PV leading to
failure of the bone marrow and severe anemia.
Splenomegaly—Abnormal enlargement of the
spleen. Splenomegaly is a major diagnostic criterion of PV.

Investigational treatment
The Food and Drug Administration (FDA) has
approved the use of anagrelide, an orphan drug, for
investigational use in the treatment of PV. Anagrelide
has moderate side effects and controls the platelet level
in over 90% of patients.
Treatment of complications
The itching caused by PV is often difficult to control. Patients with pruritus are given diphenhydramine
(Benadryl) or another antihistamine. Patients with
high levels of uric acid are usually given allopurinol
(Lopurin, Zyloprim) by mouth. Supportive care
includes advice about diet–splenomegaly often makes
patients feel full after eating only a little food. This
2970

problem can be minimized by advising patients to eat
small meals followed by rest periods.
Because of the clotting problems related to PV,
patients should not undergo surgery until their blood
counts are close to normal levels. Female patients of
childbearing age should be warned about the dangers
of pregnancy related to their clotting abnormalities.

Prognosis
The prognosis for untreated polycythemia vera is
poor; 50% of patients die within 18 months after
diagnosis. Death usually results from heart failure,
leukemia, or hemorrhage. Patients being treated for
GALE ENCYCLOPEDIA OF MEDICINE

Polydactyly and syndactyly

PV can expect to live between 11 and 15 years on
average after diagnosis.
Resources
ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Rebecca J. Frey, PhD

Polydactyly and syndactyly
Definition
Polydactyly and syndactyly are congenital irregularities of the hands and feet. Polydactyly is the occurrence
of extra fingers or toes, and syndactyly is the webbing
or fusing together of two or more fingers or toes.

Description
Polydactyly can vary from an unnoticeable rudimentary finger or toe to fully developed extra digits.
Syndactyly also exhibits a large degree of variation. Digits can be partially fused or fused along their
entire length. The fusion can be simple with the digits
connected only by skin, or it can be complicated with
shared bones, nerves, vessels, or nails.
Polydactyly and syndactyly can occur simultaneously when extra digits are fused. This condition is
known as polysyndactyly.

Causes and symptoms
Polydactyly and syndactyly are due to errors in
the process of fetal development. For example, syndactyly results from the failure of the programmed cell
death that normally occurs between digits. Most often
these errors are due to genetic defects.
Polydactyly and syndactyly can both occur by
themselves as isolated conditions or in conjunction
with other symptoms as one aspect of a multi-symptom disease. There are several forms of isolated syndactyly and several forms of isolated polydactyly; each
of these, where the genetics is understood, is caused by
an autosomal dominant gene. This means that since
GALE ENCYCLOPEDIA OF MEDICINE

Polydactyly is the occurrence of extra or partial fingers or
toes. (Custom Medical Stock Photo. Reproduced by permission.)

the gene is autosomal (not sex-linked), males and
females are equally likely to inherit the trait. This
also means that since the gene is dominant, children
who have only one parent with the trait have a 50%
chance of inheriting it. However, people in the same
family carrying the same gene can have different
degrees of polydactyly or syndactyly.
Polydactyly and syndactyly are also possible outcomes of a large number of rare inherited and developmental disorders. One or both of them can be present in
over 100 different disorders where they are minor features compared to other characteristics of these diseases.
For example, polydactyly is a characteristic of
Meckel syndrome and Laurence-Moon-Biedl syndrome.
Polydactyly may also be present in Patau’s syndrome,
asphyxiating thoracic dystrophy, hereditary spherocytic
hemolytic anemia, Moebius syndrome, VACTERL
association, and Klippel-Trenaunay syndrome.
Syndactyly is a characteristic of Apert syndrome,
Poland syndrome, Jarcho-Levin syndrome, oralfacial-digital syndrome, Pfeiffer syndrome, and
Edwards syndrome. Syndactyly may also occur with
Gordon syndrome, Fraser syndrome, Greig cephalopolysyndactyly, phenylketonuria, Saethre-Chotzen
syndrome, Russell-Silver syndrome, and triploidy.
In some isolated cases of polydactyly or syndactyly, it is not possible to determine the cause. Some of
these cases might nevertheless be due to genetic defects;
sometimes there is too little information to demonstrate
2971

Polyglandular deficiency syndromes

KEY TERMS
Autosomal chromosome—One of the non-X or
non-Y chromosomes.
Congenital—A condition present at birth.
Digit—A finger or a toe.
Dominant trait—A genetic trait that will always
express itself when present as one of a pair of
genes (as opposed to a recessive trait where two
copies of the gene are necessary to give the individual the trait).
Syndactyly is the webbing or fusing together of two or more
fingers or toes. (Photograph by Keith, Custom Medical Stock
Photo. Reproduced by permission.)

a genetic cause. Some cases might be due to external
factors like exposure to toxins or womb anomalies.

Diagnosis
Polydactyly and syndactyly can be diagnosed by
external observation, x ray, and fetal sonogram.

Treatment
Polydactyly can be corrected by surgical removal
of the extra digit or partial digit. Syndactyly can also
be corrected surgically, usually with the addition of a
skin graft from the groin.

Prognosis
The prognosis for isolated polydactyly and syndactyly is excellent. When polydactyly or syndactyly
are part of a larger condition, the prognosis depends
on the condition. Many of these conditions are quite
serious, and early death may be the probable outcome.

Prevention
There is no known prevention for these conditions.
Resources
ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914)
428-7100. resourcecenter@modimes.org.
<http://www.modimes.org>.
National Institute of Child Health and Human
Development. Bldg 31, Room 2A32, MSC 2425, 31
Center Drive, Bethesda, MD 20892-2425. (800) 5052742. <http://www.nichd.nih.gov/sids/sids.htm>.
2972

Gene—A portion of a DNA molecule that either
codes for a protein or RNA molecule or has a
regulatory function.
Triploidy—The condition where an individual has
three entire sets of chromosomes instead of the
usual two.
Trisomy—An abnormal condition where three
copies of one chromosome are present in the cells
of an individual’s body instead of two, the normal
number.

OTHER

OMIM Home Page, Online Mendelian Inheritance in Man.
<http://www.ncbi.nlm.nih.gov/Omim>.

Lorraine Lica, PhD

Polyendocrine deficiency syndromes see
Polyglandular deficiency syndromes

Polyglandular deficiency
syndromes
Definition
Polyglandular deficiency syndromes are disorders
characterized by the failure of more than one endocrine gland to make hormones in sufficient quantities
for the body to function normally.

Description
the endocrine system is a diverse group of glands
located all over the body that work together to regulate the body’s metabolic activities. It includes:
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS



the thyroid gland is located in the neck and sets the
metabolic speed of many processes,



the parathyroid glands, attached to the back of the
thyroid, regulate calcium balance,

Antibody—A weapon in the body’s immune
defense arsenal that attacks a specific antigen.
Congenital—Present at birth.



the adrenal glands are located on top of the kidneys
and make four separate kinds of hormones,



the gonads (sex organs) produce sex hormones,



the pancreas is responsible for the production of
digestive juices, insulin, and glucagon.

There are over a dozen different syndromes that
involve failure of more than one endocrine gland.

Causes and symptoms
The cause of polyglandular deficiency syndromes
is usually an autoimmune response—a condition in
which the body generates antibodies to its own tissues.
The immune system may attack one or more glands;
however, because of their inter dependence, the
destruction of one gland can often lead to the impairment of another. Other causes may include infectious
disease; insufficient blood flow to the glands due to an
obstruction such as a blood clot; or the presence of a
tumor.
Doctors usually group polyglandular deficiency
syndromes into three types:






Type I occurs during childhood and is characterized
by failure of the adrenals, parathyroids, thyroid, and
gonads combined with hepatitis, hair loss, skin pigment changes, and inability of the bowel to absorb
adequate nutrition. These children also get a persistent skin fungus infection called candidiasis.
Type II occurs during adulthood and is characterized
by failure of the adrenals, thyroid (Schmidt’s syndrome), and gonads combined with similar nutritional failures and hair and skin changes. These
patients also have myasthenia gravis. This type of
polyglandular deficiency syndrome often produces
insulin-dependent diabetes mellitus (IDDM).
Type III disease may produce diabetes or adrenal
failure combined with thyroid problems. It may
also include baldness (alopecia), anemia, and vitiligo
(condition characterized by white patches on normally pigmented skin).

Not all symptoms of any syndrome appear at once
or in the same patient.
GALE ENCYCLOPEDIA OF MEDICINE

Myasthenia gravis—A disease that causes muscle
weakness.
Rubella—German measles.
Syndrome—A collection of abnormalities that
occur often enough to suggest they have a common
cause.

Diagnosis
Because these diseases evolve over time, the final
diagnosis may not appear for years. A family history is
very helpful in knowing what to expect. Any single
endocrine abnormality should heighten suspicion that
there are others, since they so often occur together,
both as underproduction and overproduction of hormones. Most hormone levels can be monitored
through blood tests. Many of the antibodies that characterize these conditions can also be found by blood
testing.

Treatment
Fortunately there are replacements available for
all the missing hormones. Careful balancing of them
all can provide a reasonably comfortable quality of life
for these patients.
Resources
BOOKS

Sherman, Steven I., and Robert F. Gagel. ‘‘Disorders
Affecting Multiple Endocrine Systems.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony S.
Fauci, et al. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Polyhydramnios and
oligohydramnios
Definition
Polyhydramnios is a high level and oligohydramnios is low level of amniotic fluid.
2973

Polyhydramnios and oligohydramnios

the pituitary gland, located deep in the brain, is
considered the ‘‘master gland’’ that regulates many
of the others



Polyhydramnios and oligohydramnios

Description
Amniotic fluid is the liquid that surrounds the
developing fetus during pregnancy. It is contained
within the amniotic membrane that forms the amniotic sac (bag of waters). During the first three months
after conception (first trimester), amniotic fluid is
mainly derived from the blood plasma that diffuses
through the thin tissues of the fetus into the surrounding space. After the fetal kidneys form and become
functional at about 10–11 weeks, fetal urine becomes
the main source of amniotic fluid and remains so for
the rest of the pregnancy. In addition, the lungs also
produce liquid that becomes part of the amniotic fluid.
Other contributions come from fetal oral and nasal
secretions and from the fetal surface of the placenta.
Amniotic fluid removal is largely due to fetal swallowing and absorption into the fetal blood. Uptake also
occurs across the placental surface. The volume of
amniotic fluid normally increases throughout pregnancy, reaching a peak at about 32–33 weeks and
remaining fairly constant or decreasing slightly thereafter. There is a wide range of normal fluid volumes
with an average of 700–800 ml at 32–33 weeks.
Through the processes of swallowing and urination,
a fetus can recycle the entire volume in less than 24
hours. Because the normal values for amniotic fluid
volume increase during pregnancy, the actual volume
that constitutes polyhydramnios is dependent on the
gestational age of the fetus. During the last two
months of pregnancy, polyhydramnios usually refers
to amniotic fluid volumes greater than 1,700–1,900 ml.
Severe cases are associated with much greater fluid
volume excesses. The range of fluid values diagnostic
of oligohydramnios is not as wide as that for polyhydramnios. Less than 300 ml, or lower than the 5%
percentile for gestational age, is usually considered
the upper threshold.

Causes and symptoms
Polyhydramnios, also referred to as hydramnios, can have any one of a number of causes related
either to an underlying maternal or fetal condition.
Maternal diabetes, which is associated with a macrosomic (enlarged) fetus, is a common cause. The
medication lithium, used to treat depression, can
also increase amniotic fluid levels. Twin gestations
are prone to polyhydramnios. Infections passed
from mother to fetus such as rubella, cytomegalovirus, and toxoplasmosis, can also result in damage
to the fetus and elevated amniotic fluid levels.
Fetal abnormalities, including many that are lifethreatening or lead to a significant impairment in
the quality of life, are found in up to a quarter of
2974

all patients. For this reason, the initial finding of
excess amniotic fluid should be followed by thorough diagnostic studies to determine the cause and
the prognosis.
Because fetal swallowing is a major factor in
amniotic fluid removal, fetal abnormalities that
prevent fluid uptake should be investigated. These
include gastrointestinal obstructions such as esophageal atresia and duodenal atresia, as well as neurological conditions that affect swallowing including
anencephaly. Certain cardiac abnormalities, kidney
disorders, and genetic conditions such as myotonic
dystrophy and alpha-thalassemia can also cause polyhydramnios. Fetal chromosome abnormalities are
frequently associated with elevated amniotic fluid
levels. The more severe the polyhydramnios the
more likely it is that fetal abnormalities will be present. In addition, there are other, infrequent causes,
and in a number of cases, no cause can be found.
Polyhydramnios can lead to maternal abdominal
discomfort and respiratory difficulties as well as
preterm labor. When polyhydramnios is associated
with fetal abnormalities, perinatal mortality is significantly increased.
Oligohydramnios is most commonly associated
with abnormalities of the fetal kidneys. Since fetal
urine is the main source of amniotic fluid in the latter
two-thirds of pregnancy, any condition that interferes
with fetal urine production can lead to oligohydramnios. Renal agenesis, cystic kidneys, and bladder
outlet obstructions are common. Meckel-Gruber syndrome, a lethal autosomal recessive genetic disorder
featuring brain and kidney abnormalities and extra
digits is one specific cause. Placental insufficiency
and fetal growh retardation can also result in oligohydramnios. Premature rupture of membranes, especially
between 16 and 24 weeks is another cause and, because
amniotic fluid is important in lung growth, it can lead
to underdevelopment of the lungs (pulmonary hypoplasia). In general, regardless of the cause, oligohydramnios that arises early in a pregnancy, can cause
hypoplastic lungs. It can also result in space limitations within the amniotic sac that cause fetal compression and orthopedic abnormalities such as clubbed
feet in the newborn. In general, oligohydramnios
that begins near the time of delivery is associated
with a better outcome than cases than have an onset
earlier in pregnancy.

Diagnosis
In current obstetrical practice, polyhydramnios
and oligohydramnios are usually detected during a
GALE ENCYCLOPEDIA OF MEDICINE

It is extremely important that the cause of an
abnormal AFI be sought. Because of the high risk of
fetal abnormalities, detailed ultrasound exams (targeted exams) should then be performed. The mother
should be counseled about the possible complications
and offered additional testing as necessary. For example, an amniocentesis for prenatal chromosome analysis may be important because of the high risk of fetal
chromosome abnormalities. This test is usually indicated if fetal abnormalities are suspected on the basis
of the ultrasound exam. An amniocentesis can also be
used to check for fetal infections and some rare single
gene defects.

Treatment
Effective treatments for polyhydramnios and oligohydramnios are limited. To relieve maternal discomfort, an excess fluid level can be reduced by
inserting a needle into the amniotic sac and using a
syringe to withdraw excess fluid. This can be done
repeatedly, if necessary. In oligohydramnios, the
opposite approach of adding fluid either by increasing oral intake in the mother or by directly infusing
saline into the amniotic sac has been tried in select
cases. If the cause of oligohydramnios is a fetal
bladder obstruction, it may be possible to place a
small tube in the bladder to shunt the fluid into the
amniotic sac.

Alternative treatment
In select cases where polyhydramnios is thought
to be due to an increased output of fetal urine, the drug
indomethicin has been used with some success, but
there is concern about side effects, particularly on the
fetus. Another similar drug, sulindac, is currently
being investigated. If oligohydramnios is due to premature rupture of the membranes, a protocol to manage complications should be instituted.

KEY TERMS
Alpha-thalassemia—An inherited disorder that
interferes with the normal production of hemoglobin.
Anencephaly—Congenital absence of the brain.
Occurs during the first month of embryonic
development.
Autosomal recessive—A pattern of inheritance in
which both copies of an autosomal gene must be
abnormal for a genetic condition or disease to occur.
An autosomal gene is one that is located on one of
the autosomes or non-sex chromosomes. When
both parents have one abnormal copy of the same
gene, they have a 25% chance with each pregnancy
that their offspring will have the disorder.
Congenital—Present at birth.
Duodenal atresia—Closure or blockage of the duodenum, the upper section of the small intestine.
Esophageal atresia—Blockage or closure of the
esophagus, the tube leading from the mouth to the
stomach.
Gestational age—The estimated age of a fetus
expressed in weeks, calculated from the first day
of the last normal menstrual period.
Myotonic dystrophy—A genetic defect resulting in
abnormal muscle function.
Placenta—The flat, spongy structure that forms
within the uterus during pregnancy and provides
nourishment to the developing fetus.
Renal agenesis—Failure of the fetal kidneys to
form. Oligohydramnios usually associated with
absence of both kidneys.

fetal abnormality, the nature of that abnormality will
determine the prognosis. This is one reason why it is
important to perform the necessary follow-up studies.
A woman who has been diagnosed with polyhydramnios or oligohydramnios needs to be made fully aware
of the types of testing available and carefully counseled about the diagnosis and its impact on the chance
for a successful pregnancy outcome and a healthy
infant.

Prevention
Prognosis
The prognosis for both polyhydramnios and oligohydramnios depends on the cause. If excess or
reduced amniotic fluid is the result of an underlying
GALE ENCYCLOPEDIA OF MEDICINE

In order to prevent polyhydramnios or oligohydramnios, it would be necessary to prevent the
underlying cause. Good control of maternal diabetes
and the prevention of infections transmittable from
2975

Polyhydramnios and oligohydramnios

routine prenatal ultrasound. If the ultrasonographer
suspects that excess or reduced fluid is present, it is
customary to take measurements of pockets of fluid
visualized around the fetus, calculate the amniotic
fluid index (AFI), and compare it to AFI values
found in standard tables. Subsequent ultrasound measurements can then be used to track the increase or
decrease in fluid.

Polymyalgia rheumatica

mother to fetus are two approaches for a subset of
cases, but, in general, prevention is not possible.
Resources
BOOKS

Cunningham, F. Gary. Williams Obstetrics. New York;
McGraw-Hill, 2001
Rodeck, Charles H., and Martin J. Whittle. Fetal Medicine,
Basic Science and Clinical Practice. New York,
Churchill Livingstone, 1999.
PERIODICALS

Kilpactrick, Sarah J. ‘‘Therapeutic Interventions for
Oligohydramnios: Amnioinfusion and Maternal
Hydration’’ Clinical Obstetric and GYN 40, no. 2 (June
1996): 266-279.

Sallie Boineau Freeman, PhD

Polymyalgia rheumatica
Definition
Polymyalgia rheumatica is a syndrome that causes
pain and stiffness in the hips and shoulders of people
over the age of 50.

Description
Although the major characteristics of this condition are just pain and stiffness, there are reasons to
believe it is more than just old-fashioned rheumatism.
Patients are commonly so afflicted that their muscles
atrophy from disuse. A similar complaint of such
weakness is also seen in serious muscle diseases.
Moreover, some patients develop arthritis or a disease
called giant cell arteritis or temporal arteritis.

Causes and symptoms
This condition may arise as often as once in every
2,000 people. Rarely does it affect people under 50
years old. The average age is 70; women are afflicted
twice as often as men. Along with the pain and stiffness of larger muscles, headache may add to the discomfort. The scalp is often tender. Pain is usually
worse at night. There may be fever and weight loss
before the full disease appears. Patients complain that
stiffness is worse in the morning and returns if they
have been inactive for any period of time, a condition
called gelling. Sometimes the stiffness is severe enough
that it causes frozen shoulder.
2976

KEY TERMS
Anemia—A condition in which the blood lacks
enough red blood cells (hemoglobin).
Atrophy—Wasting away of a body part.
Frozen shoulder—A shoulder that becomes
scarred and cannot move.
Giant cell arteritis—Also called temporal arteritis.
A condition which causes the inflammation of temporal arteries. It can cause blindness when the
inflammation effects the ophthalmic artery.
NSAIDs—Non-steroidal anti-inflammatory drugs
like aspirin, ibuprofen, and naproxen.
Syndrome—A collection of abnormalities that
occur often enough to suggest they have a common
cause.

Diagnosis
Symptoms are usually present for over a month by
the time patients seek medical attention. A mild anemia is often is often present. One blood test, called an
erythrocyte sedimentation rate, is very high, much
more so than in most other diseases. The most important issue in evaluating polymyalgia rheumatica is to
check for giant cell arteritis. Giant cell arteritis can
lead to blindness if lift untreated.

Treatment
Polymyalgia rheumatica responds dramatically to
cortisone-like drugs in modest doses. In fact, one part
of confirming the diagnosis is to observe the response
to this treatment. It may also respond to nonsteroidal
anti-inflammatory drugs (NSAIDs). Temporal arteritis
is also treated with cortisone, but in higher doses.

Prognosis
The disease often remits after a while, with no
further treatment required.
Resources
BOOKS

Griggs, Robert C. ‘‘Episodic Muscle Spasms, Cramps,
andWeakness.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Polymyositis is an inflammatory muscle disease
causing weakness and pain. Dermatomyositis is identical to polymyositis with the addition of a characteristic skin rash.

Description
Polymyositis (PM) is an inflammatory disorder in
which muscle tissue becomes inflamed and deteriorates, causing weakness and pain. It is one of several
types of inflammatory muscle disease, or myopathy.
Others include dermatomyositis (DM) and inclusion
body myositis. All three types are progressive conditions, usually beginning in adulthood. A fourth type,
juvenile dermatomyositis, occurs in children.
Although PM and DM can occur at any age, 60% of
cases appear between the ages of 30 and 60. Females
are affected twice as often as males.

Causes and symptoms

Dermatomyositis is marked by a skin rash. The
rash is dusky, reddish, or lilac in color, and is most
often seen on the eyelids, cheeks, bridge of the nose,
and knuckles, as well as on the back, upper chest,
knees, and elbows. The rash often appears before the
muscle weakness.

Diagnosis
PM and DM are often difficult diseases to diagnose, because they are rare, because symptoms come
on slowly, and because they can be mistaken for other
diseases that cause muscle weakness, especially limb
girdle muscular dystrophy.
Accurate diagnosis involves:


A neurological exam.



Blood tests to determine the level of the muscle
enzyme creatine kinase, whose presence in the circulation indicates muscle damage.



Electromyography, an electrical test of muscle
function.



Muscle biopsy, in which a small sample of affected
muscle is surgically removed for microscopic analysis. A biopsy revealing muscle cells surrounded by
immune system cells is a strong indicator of myositis.

Causes
The cause of PM and DM is not known, but it is
suspected that a variety of factors may play a role in
the development of these diseases. PM and DM may
be autoimmune diseases, caused by the immune system’s attack on the body’s own tissue. The reason for
this attack is unknown, although some researchers
believe that a combination of immune system susceptibility and an environmental trigger may explain at
least some cases. Known environmental agents associated with PM and DM include infectious agents such
as Toxoplasma, Borrella (Lyme disease bacterium),
and coxsackievirus. Most cases, however, have no
obvious triggers (direct causative agents). There may
also be a genetic component in the development of PM
and DM.
Symptoms
The early symptoms of PM and DM are slowly
progressing muscle weakness, usually symmetrical
between the two sides of the body. PM and DM affect
primarily the muscles of the trunk and those closest to
the trunk, while the hands, feet, and face usually are
not involved. Weakness may cause difficulty walking,
standing, and lifting objects. Rarely, the muscles of
breathing may be affected. Weakness of themuscles
used for swallowing can cause difficulty with swallowing (dysphagia). Joint pain and/or swelling also may
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
PM and DM respond to high doses of immunosuppressant drugs in most cases. The most common
medication used is the corticosteroid prednisone.
Prednisone therapy usually leads to improvement
within two or three months, at which point the dose
can be tapered to a lower level to avoid the significant
side effects associated with high doses of prednisone.
Unresponsive patients are often given a replacement
or supplementary immunosuppressant, such as
azathioprine,
cyclosporine,
or
methotrexate.
Intravenous immunoglobulin treatments may help
some people who are unresponsive to other
immunosuppressants.
Pain can usually be controlled with an over-thecounter analgesic, such as aspirin, ibuprofen, or
naproxen. A speech-language therapist can help suggest exercises and tips to improve difficulty in
2977

Polymyositis

Polymyositis

be present. Later in the course of these diseases, muscle
wasting or shortening (contracture) may develop in
the arms or legs. Heart abnormalities, including electrocardiogram (ECG) changes and arrhythmias,
develop at some time during the coursed of these diseases in about 30% of patients.

Polysomnography

Prevention

KEY TERMS
Autoimmune disease—A diseases in which the
body’s immune system, responsible for fighting off
foreign invaders such as bacteria and viruses,
begins to attack and damage a part of the body as
if it were foreign.
Immunosuppressant—A drug that reduces the
body’s natural immunity by suppressing the natural
functioning of the immune system.

swallowing. Avoiding weight gain helps prevent overtaxing weakened muscles.

Alternative treatment
As with all autoimmune conditions, food allergies/intolerances and environmental triggers may be
contributing factors. For food allergies and intolerances, an elimination challenge diet can be used
under the supervision of a trained practitioner, naturopath, or nutritionist, to identify trigger foods. These
foods can then be eliminated from the person’s diet.
For environmental triggers, it is helpful to identify the
source so that it can be avoided or eliminated. A
thorough detoxification program can help alleviate
symptoms and change the course of the disease.
Dietary changes from processed foods to whole
foods that do not include allergen triggers can have
significant results. Nutrient supplements, especially
the antioxidants zinc, selenium, and vitamins A, C,
and E, can be beneficial. Constitutional homeopathic
treatment can work at a deep level to rebalance the
whole person. Acupuncture and Chinese herbs can be
effective in symptom alleviation and deep healing.
Visualization, guided imagery, and hypnosis for pain
management are also useful.

There is no known way to prevent myositis, except
to avoid exposure to those environmental agents that
may be associated with some cases.
Resources
ORGANIZATIONS

Dermatomyositis and Polymyositis Support Group. 146
Newtown Road, Southampton, SO2 9HR, U.K.
Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson, AZ 85718. (800) 572-1717. <http://
www.mdausa.org>.
Myositis Association of America. 600-D University
Boulevard, Harrisonburg, VA 22801. (540) 433-7686.
<http://www.myositis.org>.
National Institutes of Health. National Institute of Arthritis
and Musculoskeletal and Skin Diseases. 900 Rockville
Pike, Bethesda, MD 20892. (301) 496-8188. <http://
www.hih.gov.niams>.

Richard Robinson

Polyneuritis see Peripheral neuropathy

Polysomnography
Definition
The word polysomnography, derived from the
Greek roots ‘‘poly,’’ meaning many, ‘‘somno,’’ meaning sleep, and ‘‘graphy’’ meaning to write, refers to
multiple tests performed on patients while they sleep.
Polysomnography is an overnight test to evaluate
sleep disorders. Polysomnography generally includes
monitoring of the patient’s airflow through the nose
and mouth, blood pressure, electrocardiographic
activity, blood oxygen level, brain wave pattern, eye
movement, and the movement of respiratory muscle
and limbs.

Prognosis
The progression of PM and DM varies considerably from person to person. Immunosuppressants can
improve strength, although not all patients respond,
and relapses may occur. PM and DM can lead to
increasing weakness and disability, although the life
span usually is not significantly affected. About half of
the patients recover and can discontinue treatment
within five years of the onset of their symptoms.
About 20% still have active disease requiring ongoing
treatment after five years, and about 30% have inactive disease but some remaining muscle weakness.
2978

Purpose
Polysomnography is used to help diagnose and
evaluate a number of sleep disorders. For instance, it
can help diagnose sleep apnea, a common disorder in
middle-aged and elderly obese men, in which the muscles of the soft palate in the back of the throat relax
and close off the airway during sleep. This may cause
the person to snore loudly and gasp for air at night,
and to be excessively sleepy and doze off during the
day. Another syndrome often evaluated by polysomnography is narcolepsy. In narcolepsy, people have
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Polysomnography is extremely safe and no special
precautions need to be taken.

Description
Polysomnography requires an overnight stay in a
sleep laboratory. During this stay, while the patient
sleeps, he or she is monitored in a number of ways that
can provide very useful information.
One form of monitoring is electroencephalography
(EEG), in which electrodes are attached to the
patient’s scalp in order to record his or her brain
wave activity. The electroencephalograph records
brain wave activity from different parts of the brain
and charts them on a graph. The EEG not only helps
doctors establish what stage of sleep the patient is in,
but may also detect seizures.
Another form of monitoring is continuous electro-oculography (EOG), which records eye movement
and is used to determine when the patient is going
through a stage of sleep called rapid-eye-movement
(REM) sleep. Both EEG and EOG can be helpful in
determining sleep latency (the time that transpires
between lights out and the onset of sleep), total sleep
time, the time spent in each sleep stage, and the number of arousals from sleep.
The air flow through the patient’s nose and mouth
are measured by heat-sensitive devices called thermistors. This can help detect episodes of apnea (stopped
breathing), or hypnopea (inadequate breathing).
Another test called pulse oximetry measures the
amount of oxygen in the blood, and can be used to
assess the degree of oxygen starvation during episodes
of hypnopea or apnea.
The electrical activity of the patient’s heart is also
measured on an electrocardiogram, or ECG.
Electrodes are affixed to the patient’s chest and they
pick up electrical activity from various areas of the
heart. They help detect cardiac arrythmias (abnormal
GALE ENCYCLOPEDIA OF MEDICINE

heart rhythms), which may occur during periods of
sleep apnea. Blood pressure is also measured: sometimes episodes of sleep apnea can dangerously elevate
blood pressure.
In some cases, sleep laboratories monitor the
movement of limbs during sleep. This can be helpful
in detecting such sleep disorders as periodic limb
movements.

Preparation
The patient may be asked to discontinue taking
any medications used to help him/her sleep. Before the
patient goes to sleep, the technician hooks him or her
up to all of the monitors being used.

Aftercare
Once the test is over, the monitors are detached
from the patient. No special measures need to be taken
after polysomnography.

Normal results
A normal result in polysomnography shows normal results for all parameters (EEG, ECG, blood
pressure, eye movement, air flow, pulse oximetry,
etc.) monitored throughout all stages of sleep.

Abnormal results
Polysomnography may yield a number of abnormal results, indicating a number of potential disorders. For instance, abnormal transitions in and out
of various stages of sleep, as documented by the EEG
and the EOG, may be a sign of narcolepsy. Reduced
air flow through the nose and mouth, along with a fall
in oxygenation of the blood, may indicate apnea or
hypopnea. If apnea is accompanied by abnormalities
in ECG or elevations in blood pressure, this can indicate that sleep apnea may be particularly harmful.
Frequent movement of limbs may indicate a sleep
disorder called periodic limb movement.
Resources
ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222.
<http://www.nhlbi.nih.gov>.

Robert Scott Dinsmoor

Pompe’s disease see Glycogen storage
diseases
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Polysomnography

sudden attacks of sleep and/or cataplexy (temporary
loss of muscle tone caused by moments of emotion,
such as fear, anger, or surprise, which causes people to
slump or fall over), sleep paralysis or hallucinations at
the onset of sleep. Polysomnography is often used to
evaluate parasomnias (abnormal behaviors or movements during sleep), such as sleep walking, talking in
one’s sleep, nightmares, and bedwetting. It can also be
used to detect or evaluate seizures that occur in the
middle of the night, when the patient and his or her
family are unlikely to be aware of them.

Porphyrias

Porphyrias
Definition
The porphyrias are disorders in which the body
produces too much porphyrin and insufficient heme
(an iron-containing nonprotein portion of the hemoglobin molecule). Porphyrin is a foundation structure
for heme and certain enzymes. Excess porphyrins
are excreted as waste in the urine and stool.
Overproduction and overexcretion of porphyrins
causes low, unhealthy levels of heme and certain important enzymes, creating various physical symptoms.

Description
Biosynthesis of heme is a multistep process that
begins with simple molecules and ends with a large,
complex heme molecule. Each step of the chemical
pathway is directed by its own task-specific protein,
called an enzyme. As a heme precursor molecule
moves through each step, an enzyme modifies the
precursor in some way. If a precursor molecule is not
modified, it cannot proceed to the next step, causing a
buildup of that specific precursor.
This situation is the main characteristic of the
porphyrias. Owing to a defect in one of the enzymes
of the heme biosynthesis pathway, protoporphyrins or
porphyrins (heme precursors) are prevented from
proceeding further along the pathway. These precursors accumulate at the stage of the enzyme defect
causing an array of physical symptoms in an affected
person. Specific symptoms depend on the point at
which heme biosynthesis is blocked and which precursors accumulate. In general, the porphyrias primarily
affect the skin and the nervous system. Symptoms can
be debilitating or life threatening in some cases.
Porphyria is most commonly an inherited condition.
It can also, however, be acquired after exposure to
poisonous substances.
Heme
Heme is produced in several tissues in the body,
but its primary biosynthesis sites are the liver and the
bone marrow. Heme synthesis for immature red blood
cells, namely the erythroblasts and the reticulocytes,
occurs in the bone marrow.
Although production is concentrated in the liver
and bone marrow, heme is utilized in various capacities in virtually every tissue in the body. In most cells,
heme is a key building block in the construction of
factors that oversee metabolism and transport of
2980

oxygen and energy. In the liver, heme is a component
of several vital enzymes, particularly cytochrome
P450. Cytochrome P450 is involved in the metabolism
of chemicals, vitamins, fatty acids, and hormones; it is
very important in transforming toxic substances into
easily excretable materials. In immature red blood
cells, heme is the featured component of hemoglobin.
Hemoglobin is the red pigment that gives red blood
cells their characteristic color and their essential ability to transport oxygen.
Heme biosynthesis
The heme molecule is composed of porphyrin and
an iron atom. Much of the heme biosynthesis pathway
is dedicated to constructing the porphyrin molecule.
Porphyrin is a large molecule shaped like a four-leaf
clover. An iron atom is placed at its center point in the
last step of heme biosynthesis.
The production of heme may be compared to a
factory assembly line. At the start of the line, raw materials are fed into the process. At specific points along the
line, an addition or adjustment is made to further development. Once additions and adjustments are complete,
the final product rolls off the end of the line.
The heme ‘‘assembly line’’ is an eight-step process,
requiring eight different and properly functioning
enzymes:
1. delta-aminolevulinic acid synthase
2. delta-aminolevulinic acid dehydratase
3. porphobilogen deaminase
4. uroporphyrinogen III cosynthase
5. uroporphyrinogen decarboxylase
6. coproporphyrinogen oxidase
7. protoporphyrinogen oxidase
8. ferrochelatase
The control of heme biosynthesis is complex.
Various chemical signals can trigger increased or
decreased production. These signals can affect the
enzymes themselves or the production of these
enzymes, starting at the genetic level. For example,
one point at which heme biosynthesis may be controlled is at the first step. When heme levels are low,
greater quantities of delta-aminolevulinic acid (ALA)
synthase are produced. As a result, larger quantities of
heme precursors are fed into the biosynthesis pathway
to step up heme production.
Porphyrias
Under normal circumstances, when heme concentrations are at an appropriate level, precursor
GALE ENCYCLOPEDIA OF MEDICINE

The net effect of this continued production is an
abnormal accumulation of precursor molecules and
development of some type of porphyria. Each type of
porphyria corresponds with a specific enzyme defect
and an accumulation of the associated precursor.
Although there are eight steps in heme biosynthesis,
there are only seven types of porphyrias; a defect in
ALA synthase activity does not have a corresponding
porphyria.

occur. Simply inheriting this gene, however, does not
necessarily mean that a person will develop the disease. Approximately five to 10 per 100,000 people in
the United States carry a gene for AIP, but only 10%
of these people ever develop symptoms of the disease.


Hereditary coproporphyria (step 6). Hereditary
coproporphyria (HCP) is inherited in an autosomal
dominant manner. As with all porphyrias, it is an
uncommon ailment. By 1977, only 111 cases of HCP
were recorded; in Denmark, the estimated incidence
is two in one million people.



Variegate porphyria (step 7). Variegate porphyria
(VP) is also known as porphyria variegata, protocoproporphyria, South African genetic porphyria, and
Royal malady (supposedly King George III of
England and Mary, Queen of Scots, suffered from
VP). VP is inherited in an autosomal dominant manner and is especially prominent in South Africans of
Dutch descent. Among that population, the incidence is approximately three in 1,000 persons. It is
estimated that there are 10,000 cases of VP in South
Africa. Interestingly, it appears that the affected
South Africans are descendants of two Dutch settlers
who came to South Africa in 1680. Among other
populations, the incidence of VP is estimated to be
one to two cases per 100,000 persons.

Enzymes involved in heme biosynthesis display
subtle, tissue-specific variations; therefore, heme
biosynthesis may be impeded in the liver, but normal
in the immature red blood cells, or vice versa.
Incidence of porphyria varies widely between types
and occasionally by geographic location. Although
certain porphyrias are more common than others,
their greater frequency is only relative to other
types. All porphyrias are considered to be rare
disorders.
In the past, the porphyrias were divided into two
general categories based on the location of the porphyrin production. Porphyrias affecting heme biosynthesis in the liver were referred to as hepatic
porphyrias. Porphyrias that affect heme biosynthesis
in immature red blood cells were referred to as erythropoietic porphyrias (erythropoiesis is the process
through which red blood cells are produced). As of
2001, porphyrias were usually grouped into acute and
non-acute types. Acute porphyrias produce severe
attacks of pain and neurological effects. Non-acute
porphyrias present as chronic diseases.
The acute porphyrias, and the heme biosynthesis
steps at which enzyme defects occur, are:


ALA dehydratase deficiency porphyria (step 2). This
porphyria type is very rare. The inheritance pattern
appears to be autosomal recessive. In autosomal
recessively inherited disorders, a person must inherit
two defective genes, one from each parent. A parent
with only one gene for an autosomal recessive disorder does not display symptoms of the disease.



Acute intermittent porphyria (step 3). Acute intermittent porphyria (AIP) is also known as Swedish
porphyria, pyrroloporphyria, and intermittent acute
porphyria. AIP is inherited as an autosomal dominant trait, which means that only one copy of the
defective gene needs to be present for the disorder to

GALE ENCYCLOPEDIA OF MEDICINE

The non-acute porphyrias, and the steps of heme
biosynthesis at which they occur, are:


Congenital erythropoietic porphyria (step 4).
Congenital erythropoietic porphyria (CEP) is also
called Gunther’s disease, erythropoietic porphyria,
congenital porphyria, congenital hematoporphyria,
and erythropoietic uroporphyria. CEP is inherited in
an autosomal recessive manner. It is a rare disease,
estimated to affect fewer than one in one million
people. Onset of dramatic symptoms usually occurs
in infancy, but may hold off until adulthood.



Porphyria cutanea tarda (step 5). Porphyria cutanea
tarda (PCT) is also called symptomatic porphyria,
porphyria cutanea symptomatica, and idiosyncratic
porphyria. PCT may be acquired, typically as a result
of disease (especially hepatitis C), drug or alcohol
use, or exposure to certain poisons. PCT may also
be inherited as an autosomal dominant disorder,
however most people remain latent—that is, symptoms never develop. PCT is the most common of the
porphyrias, but the incidence of PCT is not well
defined.



Hepatoerythopoietic porphyria (step 5). Hepatoerythopoietic porphyria (HEP) affects heme biosynthesis in both the liver and the bone marrow.
HEP results from a defect in uroporphyrinogen
2981

Porphyrias

production decreases. However, a glitch in the biosynthesis pathway—represented by a defective
enzyme—means that heme biosynthesis does not
reach completion. Because heme levels remain low,
the synthesis pathway continues to churn out precursor molecules in an attempt to correct the heme deficit.

Porphyrias

decarboxylase activity (step 5), and is caused by
defects in the same gene as PCT. Disease symptoms,
however, strongly resemble congenital erythropoietic porphyria. HEP seems to be inherited in an autosomal recessive manner.


Erythropoietic protoporphyria (step 8). Also known
as protoporphyria and erythrohepatic protoporphyria, erythropoietic protoporphyria (EPP) is
more common than CEP; more than 300 cases have
been reported. In these cases, onset of symptoms
typically occurred in childhood.

Causes and symptoms
General characteristics
The underlying cause of all porphyrias is a defective enzyme important to the heme biosynthesis pathway. Porphyrias are inheritable conditions. In
virtually all cases of porphyria an inherited factor
causes the enzyme’s defect. An environmental trigger—such as diet, drugs, or sun exposure—may be
necessary before any symptoms develop. In many
cases, symptoms do not develop. These asymptomatic
individuals may be completely unaware that they have
a gene for porphyria.
All of the hepatic porphyrias—except porphyria
cutanea tarda—follow a pattern of acute attacks separated by periods during which no symptoms are present. For this reason, this group is often referred to as
the acute porphyrias. The erythropoietic porphyrias
and porphyria cutanea tarda do not follow this pattern
and are considered to be chronic conditions.
The specific symptoms of each porphyria vary
based on which enzyme is affected and whether that
enzyme occurs in the liver or in the bone marrow. The
severity of symptoms can vary widely, even within the
same type of porphyria. If the porphyria becomes
symptomatic, the common factor between all types is
an abnormal accumulation of protoporphyrins or
porphyrin.
ALA dehydratase porphyria (ADP)
ADP is characterized by a deficiency of ALA
dehydratase. ADP is caused by mutations in the
delta-aminolevulinate dehydratase gene (ALAD) at
9q34. Of the few cases on record, the prominent symptoms are vomiting, pain in the abdomen, arms, and
legs, and neuropathy. (Neuropathy refers to nerve
damage that can cause pain, numbness, or paralysis.)
The nerve damage associated with ADP could cause
breathing impairment or lead to weakness or paralysis
of the arms and legs.
2982

Acute intermittent porphyria (AIP)
AIP is caused by a deficiency of porphobilogen
deaminase, which occurs due to mutations in the
hydroxymethylbilane synthase gene (HMBS) located
at 11q23.3. Symptoms of AIP usually do not occur
unless a person with the deficiency encounters a
trigger substance. Trigger substances can include
hormones (for example oral contraceptives, menstruation, pregnancy), drugs, and dietary factors.
Most people with this deficiency never develop
symptoms.
Attacks occur after puberty and commonly feature severe abdominal pain, nausea, vomiting, and
constipation. Muscle weakness and pain in the back,
arms, and legs are also typical symptoms. During an
attack, the urine is a deep reddish color. The central
nervous system may also be involved. Possible psychological symptoms include hallucinations, confusion,
seizures, and mood changes.
Congenital erythropoietic porphyria (CEP)
CEP is caused by a deficiency of uroporphyrinogen III cosynthase due to mutations in the uroporphyrinogen III cosynthase gene (UROS) located at
10q25.2-q26.3. Symptoms are often apparent in
infancy and include reddish urine and possibly an
enlarged spleen. The skin is unusually sensitive to
light and blisters easily if exposed to sunlight.
(Sunlight induces protoporphyrin changes in the
plasma and skin. These altered protoporphyrin molecules can cause skin damage.) Increased hair growth is
common. Damage from recurrent blistering and associated skin infections can be severe. In some cases
facial features and fingers may be lost to recurrent
damage and infection. Deposits of protoporphyrins
can sometimes lead to red staining of the teeth and
bones.
Porphyria cutanea tarda (PCT)
PCT is caused by deficient uroporphyrinogen
decarboxylase. PCT is caused by mutations in the
uroporphyrinogen decarboxylase gene (UROD)
located at 1p34. PCT may occur as an acquired or
an inherited condition. The acquired form usually
does not appear until adulthood. The inherited form
may appear in childhood, but often demonstrates no
symptoms. Early symptoms include blistering on the
hands, face, and arms following minor injuries or
exposure to sunlight. Lightening or darkening of the
skin may occur along with increased hair growth or
loss of hair. Liver function is abnormal but the signs
are mild.
GALE ENCYCLOPEDIA OF MEDICINE

HEP is linked to a deficiency of uroporphyrinogen
decarboxylase in both the liver and the bone marrow.
HEP is an autosomal recessive disease caused by mutations in the gene responsible for PCT, the uroporphyrinogen decarboxylase gene (UROD), located at 1p34.
The gene is shared, but the mutations, inheritance, and
specific symptoms of these two diseases are different.
The symptoms of HEP resemble those of CEP.
Hereditary coproporphyria (HCP)
HCP is similar to AIP, but the symptoms are
typically milder. HCP is caused by a deficiency of
coproporphyrinogen oxidase due to mutations in a
gene by the same name at 3q12. The greatest difference
between HCP and AIP is that people with HCP may
have some skin sensitivity to sunlight. However, extensive damage to the skin is rarely seen.
Variegate porphyria (VP)
VP is caused by a deficiency of protoporphyrinogen
oxidase. There is scientific evidence that VP is caused by
mutation in the gene for protoporphyrinogen oxidase
located at 1q22. Like AIP, symptoms of VP occur only
during attacks. Major symptoms of this type of porphyria include neurological problems and sensitivity to
light. Areas of the skin that are exposed to sunlight are
susceptible to burning, blistering, and scarring.
Erythropoietic protoporphyria (EPP)
Owing to deficient ferrochelatase, the last step in
the heme biosynthesis pathway—the insertion of an
iron atom into a porphyrin molecule—cannot be completed. This enzyme deficiency is caused by mutations
in the ferrochelatase gene (FECH) located at 18q21.3.
The major symptoms of this disorder are related to
sensitivity to light—including both artificial and
natural light sources. Following exposure to light, a
person with EPP experiences burning, itching, swelling, and reddening of the skin. Blistering and scarring
may occur but are neither common nor severe. EPP is
associated with increased risks for gallstones and liver
complications. Symptoms can appear in childhood
and tend to be more severe during the summer when
exposure to sunlight is more likely.

Diagnosis
Depending on the array of symptoms an individual may exhibit, the possibility of porphyria may not
immediately come to a physician’s mind. In the
absence of a family history of porphyria, non-specific
GALE ENCYCLOPEDIA OF MEDICINE

symptoms, such as abdominal pain and vomiting, may
be attributed to other disorders. Neurological symptoms, including confusion and hallucinations, can lead
to an initial suspicion of psychiatric disease. Diagnosis
is more easily accomplished in cases in which nonspecific symptoms appear in combination with symptoms more specific to porphyria, like neuropathy,
sensitivity to sunlight, or certain other manifestations.
Certain symptoms, such as urine the color of port
wine, are hallmark signs very specific to porphyria.
DNA analysis is not yet of routine diagnostic value.
A common initial test measures protoporphyrins
in the urine. However, if skin sensitivity to light is a
symptom, a blood plasma test is indicated. If these
tests reveal abnormal levels of protoporphyrins,
further tests are done to measure heme precursor levels
in red blood cells and the stool. The presence and
estimated quantity of porphyrin and protoporphyrins
in biological samples are easily detected using spectrofluorometric testing. Spectrofluorometric testing uses
a spectrofluorometer that directs light of a specific
strength at a fluid sample. The porphyrins and protoporphyrins in the sample absorb the light energy and
fluoresce, or glow. The spectrofluorometer detects and
measures fluorescence, which indicates the amount of
porphyrins and protoporphyrins in the sample.
Whether heme precursors occur in the blood, urine,
or stool gives some indication of the type of porphyria,
but more detailed biochemical testing is required to
determine their exact identity. Making this determination yields a strong indicator of which enzyme in the
heme biosynthesis pathway is defective; which, in turn,
allows a diagnosis of the particular type of porphyria.
Biochemical tests rely on the color, chemical properties, and other unique features of each heme precursor. For example, a screening test for acute intermittent
porphyria (AIP) is the Watson-Schwartz test. In this
test, a special dye is added to a urine sample. If one of
two heme precursors—porphobilinogen or urobilinogen—is present, the sample turns pink or red. Further
testing is necessary to determine whether the precursor
present is porphobilinogen or urobilinogen—only
porphobilinogen is indicative of AIP.
Other biochemical tests rely on the fact that heme
precursors become less soluble in water (able to be
dissolved in water) as they progress further through
the heme biosynthesis pathway. For example, to determine whether the Watson-Schwartz urine test is positive for porphobilinogen or urobilinogen, chloroform is
added to the test tube. Chloroform is a water-insoluble
substance. Even after vigorous mixing, the water and
chloroform separate into two distinct layers.
2983

Porphyrias

Hepatoerythopoietic porphyria (HEP)

Porphyrias

Urobilinogen is slightly insoluble in water, while porphobilinogen tends to be water soluble. The porphobilinogen mixes more readily in water than chloroform,
so if the water layer is pink (from the dye added to the
urine sample), that indicates the presence of porphobilinogen, and a diagnosis of AIP is probable.
As a final test, measuring specific enzymes and
their activities may be done for some types of porphyrias; however, such tests are not done as a screening
method. Certain enzymes, such as porphobilinogen
deaminase (the defective enzyme in AIP), can be easily
extracted from red blood cells; other enzymes, however, are less readily collected or tested. Basically, an
enzyme test involves adding a certain amount of the
enzyme to a test tube that contains the precursor it is
supposed to modify. Both the production of modified
precursor and the rate at which it appears can be
measured using laboratory equipment. If a modified
precursor is produced, the test indicates that the
enzyme is doing its job. The rate at which the modified
precursor is produced can be compared to a standard
to measure the efficiency of the enzyme.

Treatment
Treatment for porphyria revolves around avoiding acute attacks, limiting potential effects, and treating symptoms. Treatment options vary depending on
the specific type of porphyria diagnosed. Gene therapy
has been successful for both CEP and EPP. In the
future, scientists expect development of gene therapy
for the remaining porphyrias. Given the rarity of ALA
dehydratase porphyria, definitive treatment guidelines
for this rare type have not been developed.
Acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria
Treatment for acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria
follows the same basic regime. A person who has
been diagnosed with one of these porphyrias can
prevent most attacks by avoiding precipitating factors, such as certain drugs that have been identified
as triggers for acute porphyria attacks. Individuals
must maintain adequate nutrition, particularly with
respect to carbohydrates. In some cases, an attack
can be stopped by increasing carbohydrate consumption or by receiving carbohydrates intravenously. In
2004, a report from Turkey revealed successful treatment of an acute intermittent porphyria attack with a
drug called fluoxetine.
When attacks occur prompt medical attention is
necessary. Pain is usually severe, and narcotic
2984

analgesics are the best option for relief.
Phenothiazines can be used to counter nausea, vomiting, and anxiety, and chloral hydrate or diazepam is
useful for sedation or to induce sleep. Hematin, a drug
administered intravenously, may be used to halt an
attack. Hematin seems to work by signaling the pathway of heme biosynthesis to slow production of precursors. Women, who tend to develop symptoms more
frequently than men owing to hormonal fluctuations,
may find ovulation-inhibiting hormone therapy to be
helpful.
Gene therapy is a possible future treatment for
these porphyrias. An experimental animal model of
AIP has been developed and research is in progress.
Congenital erythropoietic porphyria
The key points of congenital erythropoietic porphyria treatment are avoiding exposure to sunlight
and prevention of skin trauma or skin infection.
Liberal use of sunscreens and consumption of betacarotene supplements can provide some protection
from sun-induced damage. Medical treatments such
as removing the spleen or administering transfusions
of red blood cells can create short-term benefits, but
these treatments do not offer a cure. Remission can
sometimes be achieved after treatment with oral doses
of activated charcoal. Severely affected patients may
be offered bone marrow transplantation which
appears to confer long-term benefit.
Porphyria cutanea tarda
As with other porphyrias, the first line of defense
is avoidance of factors, especially alcohol, that could
bring about symptoms. Regular blood withdrawal is a
proven therapy for pushing symptoms into remission.
If an individual is anemic or cannot have blood drawn
for other reasons, chloroquine therapy may be used.
Erythropoietic protoporphyria
Avoiding sunlight, using sunscreens, and taking
beta-carotene supplements are typical treatment
options for erythropoietic protoporphyria. The drug
cholestyramine may reduce the skin’s sensitivity to
sunlight as well as the accumulated heme precursors
in the liver. Liver transplantation has been used in cases
of liver failure. In 2004, a report in a medical journal
told of one case of successful treatment of a 19-yearold patient with acute intermittent porphyria with
liver transplantation. While she had only been studied
for 1.5 years, the authors said her quality of life was
good and they hoped that the procedure would offer
cure for select patients with severe forms of the disease.
GALE ENCYCLOPEDIA OF MEDICINE

Acute porphyria attacks can be life-threatening
events, so attempts at self-treatment can be dangerous.
Alternative treatments can be useful adjuncts to conventional therapy. For example, some people may find
relief for the pain associated with acute intermittent
porphyria, hereditary coproporphyria, or variegate
porphyria through acupuncture or hypnosis.
Relaxation techniques, such as yoga or meditation,
may also prove helpful in pain management.

Prognosis
Even when porphyria is inherited, symptom development depends on a variety of factors. In the majority
of cases, a person remains asymptomatic throughout
life. About one percent of acute attacks can be fatal.
Other symptoms may be associated with temporarily
debilitating or permanently disfiguring consequences.
Measures to avoid these consequences are not always
successful, regardless of how diligently they are pursued. Although pregnancy has been known to trigger
porphyria attacks, dangers associated with pregnancy
as not as great as was once thought.

Prevention
For the most part, the porphyrias are attributable
to inherited genes; such inheritance cannot be prevented. However, symptoms can be limited or prevented
by avoiding factors that trigger symptom development.
People with a family history of an acute porphyria
should be screened for the disease. Even if symptoms
are absent, it is useful to know about the presence of
the gene to assess the risks of developing the associated
porphyria. This knowledge also reveals whether a person’s offspring may be at risk. Prenatal testing for
certain porphyrias is possible. Prenatal diagnosis of
congenital erythropoietic porphyria has been successfully accomplished. Any prenatal tests, however,
would not indicate whether a child would develop
porphyria symptoms; only that the potential is there.

KEY TERMS
Autosomal dominant—A pattern of genetic inheritance in which only one abnormal gene is needed
to display the trait or disease.
Autosomal recessive—A pattern of genetic inheritance in which two abnormal genes are needed to
display the trait or disease.
Biosynthesis—The manufacture of materials in a
biological system.
Bone marrow—A spongy tissue located in the hollow centers of certain bones, such as the skull and
hip bones. Bone marrow is the site of blood cell
generation.
Enzyme—A protein that catalyzes a biochemical
reaction or change without changing its own structure or function.
Erythropoiesis—The process through which new red
blood cells are created; it begins in the bone marrow.
Erythropoietic—Referring to the creation of new
red blood cells.
Gene—A building block of inheritance, which
contains the instructions for the production of a
particular protein, and is made up of a molecular
sequence found at a section of DNA. Each gene is
found on a precise location on a chromosome.
Hematin—A drug administered intravenously to
halt an acute porphyria attack. It causes heme biosynthesis to decrease, preventing the further accumulation of heme precursors.
Heme—The iron-containing molecule in hemoglobin that serves as the site for oxygen binding.
Hemoglobin—Protein-iron compound in the blood
that carries oxygen to the cells and carries carbon
dioxide away from the cells.
Hepatic—Referring to the liver.
Neuropathy—A condition caused by nerve damage.
Major symptoms include weakness, numbness,
paralysis, or pain in the affected area.

BOOKS

Porphyrin—A large molecule shaped like a fourleaf clover. Combined with an iron atom, it forms a
heme molecule.

Deats-O’Reilly, Diana. Porphyria: The UnknownDisease.
Grand Forks, N.D.: Porphyrin Publications Press/
Educational Services,1999.

Protoporphyrin—A precursor molecule to the porphyrin molecule.

Resources

PERIODICALS

‘‘Fluoxetine Treats Acute Intermittent Porphyria Safely and
Effectively.’’ Drug Week January 16, 2004: 292.
Gordon, Neal. ‘‘The Acute Porphyrias.’’ Brain &
Development 21 (September 1999): 373–77.
GALE ENCYCLOPEDIA OF MEDICINE

Thadani, Helen, et al. ‘‘Diagnosis and Management of
Porphyria.’’British Medical Journal 320 (June 2000):
1647–51.

2985

Porphyrias

Alternative treatment

Portal vein bypass

Zahir, Soonawalla F., et al. ‘‘Liver Transplantation as a
Cure for Acute Intermittent Porphyria.’’ The Lancet
February 28, 2004: 705.
ORGANIZATIONS

American Porphyria Foundation. PO Box 22712, Houston,
TX 77227. (713) 266-9617. <http://
www.enterprise.net/apf/>.
OTHER

Gene Clinics. <http://www.geneclinics.org>.
National Institute of Diabetes & Digestive &
KidneyDiseases. <http://www.niddk.nih.gov>.
Online Mendelian Inheritance in Man (OMIM).
<http://www3.ncbi.nlm.nih.gov/Omim>.

Julia Barrett
Judy C. Hawkins, MS
Teresa G. Odle

Port-wine stain see Birthmarks
Portacaval shunting see Portal vein bypass
Portal-systemic encephalopathy see Liver
encephalopathy

KEY TERMS
Cirrhosis—A chronic degenerative liver disease
common among alcoholics.
Inferior vena cava—A large vein that returns blood
from the legs, pelvis, and abdomen to the heart.
Portal vein—Formed by a fusion of small veins that
end in a network of capillaries, the portal vein
delivers blood to the liver.

Precautions
Most patients who need portal vein bypass surgery not only have liver disease and poor liver function, but also suffer from an enlarged spleen, jaundice,
and damage to the vascular system brought on by
years of alcoholism. They are likely to experience serious complications during surgery. Some patients are
aggressively uncooperative with medical personnel.
Under these conditions, half the patients may not
survive the operation.

Description

Portal vein bypass
Definition
Portal vein bypass surgery diverts blood from the
portal vein into another vein. It is performed when
pressure in the portal vein is so high that it causes
internal bleeding from blood vessels in the esophagus.

Purpose
The portal vein carries blood from the stomach and
abdominal organs to the liver. It is a major vein that
splits into many branches. High pressure in the portal
vein causes swelling and bleeding from blood vessels in
the esophagus. This situation occurs when the liver is
damaged from cirrhosis of the liver, a condition usually
caused by prolonged, excessive alcohol consumption.
Massive internal bleeding caused by high pressure
in the portal vein occurs in about 40% of patients with
cirrhosis. It is initially fatal in at least half of these
patients. Patients who survive are likely to experience
bleeding recurrence. Portal vein bypass, also called
portacaval shunting, is performed on these surviving
patients to control bleeding.
2986

A choice of portal vein bypasses is available.
Portal vein bypass is usually performed as an emergency operation in a hospital under general anesthesia.
The surgeon makes an abdominal incision and finds
the portal vein. In portacaval shunting, blood from the
portal vein is diverted into the inferior vena cava. This
is the most common bypass. In splenorenal shunting,
the splenic vein (a part of the portal vein), is connected
to the renal vein. A mesocaval shunt connects the
superior mesenteric vein (another part of the portal
vein) to the inferior vena cava.
Portal pressure can also be reduced in a procedure
called transvenous intrahepatic portosystemic shunt
(TIPS). A catheter is threaded into the portal vein,
and an expandable balloon or wire mesh is inserted
to divert blood from the portal vein to the hepatic
vein. The rate of serious complications in TIPS is
only 1–2%. The operation cannot be performed at
all hospitals, but is becoming the preferred treatment
for reducing portal pressure.

Preparation
Standard preoperative blood and urine tests are
performed, and liver function is evaluated. The heart
and arterial blood pressure are monitored both during
and after the operation.
GALE ENCYCLOPEDIA OF MEDICINE

Positron emission tomography (PET)

Aftercare
The patient will be connected to a heart monitor
and fed through a nasogastric tube. Vital functions are
monitored through blood and urine tests. Patients
receive pain medication and antibiotics. Once released
from the hospital, patients are expected to abstain
from alcohol and follow a diet and medication schedule designed to reduce the risks of re-bleeding.

Risks
Portal vein bypass surgery is high risk because it is
performed on patients who are generally in poor
health. Only half the patients survive, although the
chances of survival are greater with TIPS surgery.
Those patients who survive the operation still face
the risk of heart failure, brain disease due to a decrease
in the liver’s conversion of waste products (liver
encephalopathy), hemorrhage, lung complications,
infection, coma, and death.

Normal results
The survival rate is directly related to the amount of
liver damage patients have. The less damage, the more
likely the patient is to recover. Cooperation with restrictions on alcohol and diet affect long-term survival.
Resources
BOOKS

McPhee, Stephen, et al., editors. Current Medical Diagnosis
and Treatment, 1998. 37th ed. Stamford: Appleton &
Lange, 1997.

Tish Davidson, A.M.

Positron emission tomography
(PET)
Definition
Positron emission tomography (PET) is a scanning technique used in conjunction with small
amounts of radiolabeled compounds to visualize
brain anatomy and function.

Purpose
PET was the first scanning method to provide
information on brain function as well as anatomy.
This information includes data on blood flow, oxygen
GALE ENCYCLOPEDIA OF MEDICINE

A PET scan showing brain activity while patient recognizes
faces—left sides at left/right sides at right. Activity is prevalent in temporal lobe (bottom scans). (Photo Researchers.
Reproduced by permission.)

consumption, glucose metabolism, and concentrations of various molecules in brain tissue.
PET has been used to study brain activity in
various neurological diseases and disorders, including
stroke; epilepsy; Alzheimer’s disease, Parkinson’s
disease, and Huntington’s disease; and in some psychiatric disorders, such as schizophrenia, depression, obsessive-compulsive disorder, attention-deficit/hyperactivity
disorder, and Tourette syndrome. PET studies have
helped to identify the brain mechanisms that operate
in drug addiction, and to shed light on the mechanisms
by which individual drugs work. PET is also proving to
be more accurate than other methods in the diagnosis
of many types of cancer. In the treatment of cancer,
PET can be used to determine more quickly than conventional tests whether a given therapy is working. PET
scans also give accurate and detailed information on
heart disease, particularly in women, in whom breast
tissue can interfere with other types of tests.

Description
A very small amount of a radiolabeled compound is inhaled by or injected into the patient.
The injected or inhaled compound accumulates in
the tissue to be studied. As the radioactive atoms in
the compound decay, they release smaller particles
called positrons, which are positively charged. When
2987

Post-concussion syndrome

KEY TERMS
Electron—One of the small particles that make up
an atom. An electron has the same mass and
amount of charge as a positron, but the electron
has a negative charge.
Gamma ray—A high-energy photon, emitted by
radioactive substances.
Half-life—The time required for half of the atoms in
a radioactive substance to disintegrate.
Photon—A light particle.
Positron—One of the small particles that make up
an atom. A positron has the same mass and amount
of charge as an electron, but the positron has a
positive charge.

a positron collides with an electron (negatively
charged), they are both annihilated, and two
photons (light particles) are emitted. The photons
move in opposite directions and are picked up by
the detector ring of the PET scanner. A computer
uses this information to generate three-dimensional,
cross-sectional images that represent the biological
activity where the radiolabeled compound has
accumulated.
A related technique is called single photon emission
computed tomography (CT) scan (SPECT). SPECT is
similar to PET, but the compounds used contain
heavier, longer-lived radioactive atoms that emit
high-energy photons, called gamma rays, instead of
positrons. SPECT is used for many of the same applications as PET, and is less expensive than PET, but the
resulting picture is usually less sharp than a PET image
and reveals less information about the brain.

Risks
Some of radioactive compounds used for PET or
SPECT scanning can persist for a long time in the
body. Even though only a small amount is injected
each time, the long half-lives of these compounds
can limit the number of times a patient can be
scanned.
Resources
PERIODICALS

‘‘Studies Argue for Wider Use of PET for Cancer Patients.’’
Cancer Weekly Plus December 15, 1997: 9.

Lisa Christenson, PhD
2988

Post-concussion syndrome
Definition
Post-concussion syndrome (PCS) is a common
but controversial disorder that presents with variety
of symptoms including—but not limited to—headache, dizziness, fatigue, and personality changes.

Description
PCS occurs in approximately 23–93% of persons with mild to severe head injuries. It is estimated that a neurologist (a physician who
specializes in nerve and brain disorders) sees five
patients with PCS per month. There is no accurate
correlation between the severity of injury and the
development of PCS symptoms, since signs of the
disorder can occur in someone who was just dazed
by an injury. Some studies suggest that PCS symptoms occur at a higher rate in patients who were
unconscious after trauma.

Causes and symptoms
PCS is most commonly caused by minor head
injury called a concussion. The majority of patients
with minor head injury characteristically develop
PCS with distinct symptoms. Patients may report
problems with concentration, recent memory, and
abstract thinking. Additionally, patients may
develop dizziness, irritability, fatigue, and personality changes. Elderly patients are particularly affected
by disequilibrium and chronic dizziness even after
minor trauma.

Diagnosis
There are no specific or reliable tests to diagnose
PCS. A neuropsychologist can perform an in-depth
neuropsychologic assessment that can determine presence or absence and extent of impairment. These tests
may be performed for medical purposes.

Treatment
Treatment for PCS can be extensive. Medications
for headache and pain may be indicated (analgesics
and muscle relaxants). Antidepressants may be given
to improve insomnia, irritability, or anxiety. Pain control could be achieved with acupuncture, nerve blocks,
or transcutaneous electrical nerve stimulation (TENS,
electrical stimulation of muscle groups). It is important for clinicians to educate caretakers and to provide
GALE ENCYCLOPEDIA OF MEDICINE

Disequilibrium—Difficulty with equilibrium that
can mean a deficiency in balance and/or orientation.
Neuropsychologist—A clinical psychologist who
specializes in assessing psychological status
caused by a brain disorder.

referrals for family therapy and cognitive rehabilitation for the affected person.

Prognosis
The overall outcome is difficult to assess. Limited
interpretation in literature is primarily due to the subjective nature of symptoms. Patient recovery is directed
and evaluated by cognitive function changes, subjective
symptoms, and return to work. Most cases of PCS can
be a financial strain and threaten family stability. There
may be compensation and litigation claims, which is
often stressful and aggravates symptoms.
Resources
BOOKS

Coper, Paul R., and John G. Golfinos, et al, editors.
HeadInjury. 4th ed. New York: McGraw-Hill, 2000.
Goetz, Christopher G., et al., editors. Textbook of Clinical
Neurology. 1st ed. Philadelphia: W. B. Saunders
Company, 1999.
Goldman, Lee, et al. Cecil’s Textbook of Medicine. 21st ed.
Philadelphia: W. B. Saunders Company, 2000.

Laith Farid Gulli, M.D.

Post-herpetic neuralgia see Neuralgia

Post-traumatic stress disorder
Definition
Post-traumatic stress disorder (PTSD) is a debilitating psychological condition triggered by a major
traumatic event, such as rape, war, a terrorist act,
death of a loved one, a natural disaster, or a catastrophic accident. It is marked by upsetting memories
or thoughts of the ordeal, ‘‘blunting’’ of emotions,
increased arousal, and sometimes severe personality
changes.
GALE ENCYCLOPEDIA OF MEDICINE

Officially termed post-traumatic stress disorder
since 1980, PTSD was once known as shell shock or
battle fatigue because of its more common manifestation in war veterans. However in the past 20 years,
PTSD has been diagnosed in rape victims and victims
of violent crime; survivors of natural disasters; the
families of loved ones lost in the downing of Flight
103 over Lockerbie, Scotland; and survivors of the
1993 World Trade Center bombing, the 1995
Oklahoma City bombing, the random school and
workplace shootings, and the release of poisonous
gas in a Japanese subway; and, most recently, in the
September 11, 2001, World Trade Center and
Pentagon terrorist attacks. PTSD can affect adults of
all ages. Statistics gathered from past events indicate
that the risk of PTSD increases in order of the following factors.


female gender



middle-aged (40 to 60 years old)



little or no experience coping with traumatic events



ethnic minority



lower socioeconomic status (SES)



children in the home



women with spouses exhibiting PTSD symptoms



pre-existing psychiatric conditions



primary exposure to the event including injury, lifethreatening situation, and loss



living in traumatized community

For example, over a third of the Oklahoma City
bombing survivors developed PTSD and over half
showed signs of anxiety, depression, and alcohol
abuse. Over one year later, Oklahomans in general
had a increased use of alcohol and tobacco products,
as well as PTSD symptoms.
Children are also susceptible to PTSD and their
risk is increased exponentially as their exposure to the
event increases. Children experiencing abuse, the
death of a parent, or those located in a community
suffering a traumatic event can develop PTSD. Two
years after the Oklahoma City bombing, 16% of children in a 100 mile radius of Oklahoma City with no
direct exposure to the bombing had increased symptoms of PTSD. Weak parental response to the event,
having a parent suffering from PTSD symptoms, and
increased exposure to the event via the media all
increase the possibility of the child developing PTSD
symptoms.
2989

Post-traumatic stress disorder

Description

KEY TERMS

Post-traumatic stress disorder

Causes and symptoms
Specific causes for the onset of PTSD following a
trauma aren’t clearly defined, although experts suspect it may be influenced both by the severity of the
event, by the person’s personality and genetic makeup, and by whether or not the trauma was expected.
First response emergency personnel and individuals
directly involved in the event or those children and
families who have lost loved ones are more likely to
experience PTSD. Natural disasters account for about
a 5% rate of PTSD, while there is a 50% rate of PTSD
among rape and Holocaust survivors.
Media coverage plays a new role in both adult and
pediatric onset of PTSD symptoms. The heightened
level of news footage of actual traumatic events, such
as the Oklahoma City bombing and the terrorist
attack on the World Trade Center and the Pentagon,
increases the exposure to the violence, injury, and
death associated with the event and may reinforce
PTSD symptoms in individuals, especially young children who cannot distinguish between the actual event
and the repeated viewing of the event in the media.
PTSD symptoms are distinct and prolonged stress
reactions that naturally occur during a highly stressful
event. Common symptoms are:

for minutes or hours at a time, believing that the
traumatizing event is actually happening all over
again.
For a diagnosis of PTSD, symptoms must include
at least one of the following so-called ‘‘intrusive’’
symptoms:


flashbacks



sleep disorders: nightmares or night terrors



intense distress when exposed to events that are associated with the trauma

In addition, the person must have at least three of
the following ‘‘avoidance’’ symptoms that affect interactions with others:


trying to avoid thinking or feeling about the trauma



inability to remember the event



inability to experience emotion, as well as a loss of
interest in former pleasures (psychic numbing or
blunting)



a sense of a shortened future

Finally, there must be evidence of increased arousal, including at least two of the following:



hyperalertness



problems falling asleep



fear and anxiety





nightmares and flashbacks

startle reactions: hyperalertness and strong reactions
to unexpected noises



sight, sound, and smell recollection



memory problems



avoidance of recall situations



concentration problems



anger and irritability



moodiness



guilt



violence



depression



increased substance abuse



negative world view



decreased sexual activity

Symptoms usually begin within three months of
the trauma, although sometimes PTSD doesn’t
develop until years after the initial trauma occurred.
Once the symptoms begin, they may fade away again
within six months. Others suffer with the symptoms
for far longer and in some cases, the problem may
become chronic.
Among the most troubling symptoms of PTSD
are flashbacks, which can be triggered by sounds,
smells, feelings, or images. During a flashback, the
person relives the traumatic event and may completely
lose touch with reality, suffering through the trauma
2990

In addition to the above symptoms, children with
PTSD may experience learning disabilities and memory or attention problems. They may become more
dependent, anxious, or even self-abusing.
Recovery may be slowed by injuries, damage to
property, loss of employment, or other major problems in the community due to disaster.

Diagnosis
Not every person who experiences a traumatic
event will experience PTSD. A mental health professional will diagnose the condition if the symptoms of
stress last for more than a month after a traumatic
event. While a formal diagnosis of PTSD is made only
in the wake of a severe trauma, it is possible to have a
mild PTSD-like reaction following less severe stress.
GALE ENCYCLOPEDIA OF MEDICINE

Several factors have shown to be important in the
treatment of post-traumatic stress. These include
proximity of the treatment to the site of the event,
immediate intervention of therapy as soon as possible,
and the expectation that the individual will eventually
return to more normal functions. The most helpful
treatment of prolonged PTSD appears to be a combination of medication along with supportive and
cognitive-behavioral therapies.
Emergency care
Immediate intervention is important for individuals directly affected by the traumatic event.
Emergency care workers focus on achieving the following during the hours and days following the trauma.


protect survivors from further danger



treat immediate injuries



provide food, shelter, fluids, and clothing



provide safe zone



locate separated loved ones



reconnect loved ones



provide normal social contact



help reestablish routines



help resolve transportation, housing, or other issues
caused by disaster



provide grief counseling, stress reduction, and other
consultation to enable survivors and families to
return to normal life

As well as providing care to others, emergency personnel often need the same support as the survivors.
Operational debriefing is used to organize the emergency
response and to disseminate information and sense of
purpose to the first responders. Critical Incident Stress
Debriefing (CISD) is a formal group invention designed
to include various crisis intervention, such as information disbursement, one-on-one counseling, consultation,
family crisis intervention, and referrals. CISD is not
useful for survivors and is an interim support for first
responders until they are able to receive therapy.
Medications
Medications used to reduce the symptoms of PTSD
include anxiety-reducing medications and antidepressants, especially the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) and sertraline
HCl (Zoloft). In 2001, the U.S. Food and Drug
Administration (FDA) approved Zoloft as a long-term
GALE ENCYCLOPEDIA OF MEDICINE

treatment for PTSD. In a controlled study, Zoloft was
effective in safely improving symptoms of PTSD over a
period of 28 weeks and reducing the risk of relapse.
Sleep problems can be lessened with brief treatment with an anti-anxiety drug, such as a benzodiazepine like alprazolam (Xanax), but long-term usage can
lead to disturbing side effects, such as increased anger,
drug tolerance, dependency, and abuse.
Therapy
Several types of therapy may be useful and they
are often combined in a multi-faceted approach to
understand and treat this condition.


Cognitive-behavioral therapy focuses on changing
specific actions and thoughts through repetitive
review of traumatic events, identification of negative
behaviors and thoughts, and stress management.



Group therapy has been useful in decreasing psychological distress, depression, and anxiety in some
PTSD sufferers such as sexually abused women and
war veterans.



Psychological debriefing has been widely used to
treat victims of natural disasters and other traumatic
events such as bombings and workplace shootings,
however, recent research shows that psychological
debriefing may increase the stress response. Since
this type of debriefing focuses on the emotional
response of the survivor, it is not recommended for
individuals experiencing an extreme level of grief.

Alternative treatment
Several means of alternative treatment may be
helpful in combination with conventional therapy for
reduction of the symptoms of post-traumatic stress
disorder. These include relaxation training, breathing
techniques, spiritual treatment, and drama therapy
where the event is re-enacted.

Prognosis
The severity of the illness depends in part on
whether the trauma was unexpected, the severity of
the trauma, how chronic the trauma was (such as for
victims of sexual abuse), and the person’s readiness to
embrace the recovery process. With appropriate medication, emotional support, counseling, and follow-up
care, most people show significant improvement.
However, prolonged exposure to severe trauma, such
as experienced by victims of prolonged physical or
sexual abuse and survivors of the Holocaust, may
cause permanent psychological scars.
2991

Post-traumatic stress disorder

Treatment

Postmenopausal bleeding

KEY TERMS
Benzodiazepine—A class of drugs that have a hypnotic and sedative action, used mainly as tranquilizers to control symptoms of anxiety.
Cognitive-behavioral therapy—A type of psychotherapy used to treat anxiety disorders (including
PTSD) that emphasizes behavioral change, together
with alteration of negative thought patterns.
Selective serotonin reuptake inhibitor (SSRI)—A
class of antidepressants that work by blocking the
reabsorption of serotonin in the brain, raising the
levels of serotonin. SSRIs include Prozac, Zoloft,
and Paxil.

Prevention
More studies are needed to determine if PTSD can
actually be prevented. Some measures that have been
explored include controlling exposure to traumatic
events through safety and security measures, psychological preparation for individuals who will be
exposed to traumatic events (i.e. policemen, paramedics, soldiers), and stress inoculation training (rehearsal of the event with small doses of the stressful
situation).
Resources
PERIODICALS

DiGiovanni, C. ‘‘Domestic Terrorism with Chemical or
Biological Agents: Psychiatric Aspects.’’ American
Journal of Psychiatry 156 (1999): 1500-1505.
North, C., S. Nixon, S. Hariat, S. Mallonee, et al.
‘‘Psychiatric Disorders Among Survivors of the
Oklahoma City Bombing.’’ Journal of the American
Medical Association 282 (1999): 755-762.
Pfefferbaum, B., R. Gurwitch, N. McDonald, et al.
‘‘Posttraumatic Stress Among Children After the Death
of a Friend or Acquaintance in a Terrorist Bombing.’’
Psychiatric Services 51 (2000): 386-388.
‘‘Sertraline HCl Approved for Long-Term Use.’’ Women’s
Health Weekly September 20, 2001.
Sloan, M. ‘‘Response to Media Coverage of Terrorism’’
Journal of Conflict Resolution 44 (2000): 508-522.
Smith, D, E. Christiansen, R. Vincent, and N. Hann.
‘‘Population Effects of the Bombing of Oklahoma
City.’’ Journal of Oklahoma State Medical Association
92 (1999): 193-198.
ORGANIZATIONS

American Psychiatric Association. 1400 K St., NW,
Washington, DC 20005.

2992

Anxiety Disorders Association of America. 11900 Parklawn
Dr., Ste. 100, Rockville, MD 20852. (301) 231-9350.
Freedom From Fear. 308 Seaview Ave., Staten Island, NY
10305. (718) 351-1717.
National Anxiety Foundation. 3135 Custer Dr., Lexington,
KY 40517. (606) 272-7166.
National Center for Post-Traumatic Stress Disorder.
<http://www.dartmouth.edu/dms/ptsd>.
National Institute of Mental Health. Rm 15C-05, 5600
Fishers Lane, Rockville, MD 20857.
Society for Traumatic Stress Studies, 60 Revere Dr., Ste.
500, Northbrook, IL 60062. (708) 480-9080.

Jacqueline L. Longe
Jill Granger, MS

Postmenopausal bleeding
Definition
Postmenopausal bleeding is bleeding from the
reproductive system that occurs six months or more
after menstrual periods have stopped due to menopause.

Description
Menopause, the end of ovulation and menstrual
periods, naturally occurs for most women age 40–55
years. The process of ending ovulation and menstruation is gradual, spanning one to two years.
Postmenopausal bleeding is bleeding that occurs
after menopause has been established for at least six
months. It is different from infrequent, irregular periods (oligomenorrhea) that occur around the time of
menopause.
Many women experience some postmenopausal
bleeding. However, postmenopausal bleeding is not
normal. Because it can be a symptom of a serious
medical condition, any episodes of postmenopausal
bleeding should be brought to the attention of a
woman’s doctor.
Women taking estrogen (called hormone replacement therapy or HRT) are more likely to experience
postmenopausal bleeding. So are obese women,
because fat cells transform male hormones (androgens) secreted by the adrenal gland into estrogen.

Causes and symptoms
Postmenopausal bleeding can originate in different parts of the reproductive system. Bleeding from
GALE ENCYCLOPEDIA OF MEDICINE

Lesions and cracks on the vulva may also bleed.
Sometimes bleeding occurs after intercourse. Bleeding
can occur with or without an associated infection.
Bleeding from the upper reproductive system can
be caused by:


hormone replacements



endometrial cancer



endometrial polyps



cervical cancer



cervical lesions



uterine tumors



ovarian cancer



estrogen-secreting tumors in other parts of the body

The most common cause of postmenopausal
bleeding is HRT. The estrogen in the replacement
therapy eases the symptoms of menopause (like hot
flashes), and decreases the risk of osteoporosis.
Sometimes this supplemental estrogen stimulates the
uterine lining to grow. When the lining is shed, postmenopausal bleeding occurs. Most women on HRT
usually take the hormone progesterone with the estrogen, and may have monthly withdrawal bleeding. This
is a normal side effect.
About 5–10% of postmenopausal bleeding is due
to endometrial cancer or its precursors. Uterine hyperplasia, the abnormal growth of uterine cells, can be a
precursor to cancer.

Invasive diagnostic procedures
Endometrial biopsy allows the doctor to sample
small areas of the uterine lining, while cervical biopsy
allows the cervix to be sampled. Tissues are then
examined for any abnormalities. This is a simple office
procedure.
Dilatation and curettage (D & C) is often necessary
for definitive diagnosis. This is done under either general or local anesthesia. After examining the tissues
collected by an endometrial biopsy or D & C, the
doctor may order additional tests to determine if an
estrogen-secreting tumor is present on the ovaries or in
another part of the body.
Non-invasive diagnostic procedures
With concerns about the rising cost of health care,
vaginal probe ultrasound is increasingly being used
more than endometrial biopsy to evaluate women
with postmenopausal bleeding. Vaginal ultrasound
measures the thickness of the endometrium. When
the endometrial stripe is less than 0.2 in (5 mm)
thick, the chance of cancer is less than 1%. The disadvantage of vaginal ultrasound is that it often does
not show polyps and fibroids in the uterus.
A refinement of vaginal probe ultrasound is saline
infusion sonography (SIS). A salt water (saline) solution is injected into the uterus with a small tube (catheter) before the vaginal probe is inserted. The presence
of liquid in the uterus helps make any structural
abnormalities more distinct. These two non-invasive
procedures cause less discomfort than endometrial
biopsies and D & Cs, but D & C still remains the
definitive test for diagnosing uterine cancer.

Treatment
Diagnosis
Diagnosis of postmenopausal bleeding begins
with the patient. The doctor will ask for a detailed
history of how long postmenopausal bleeding has
occurred. A woman can assist the doctor by keeping
a record of the time, frequency, length, and quantity of
bleeding. She should also tell the doctor about any
medications she is taking, especially any estrogens or
steroids.
After taking the woman’s history, the doctor does
a pelvic examination and Pap test. The doctor will
examine the vulva and vagina for signs of atrophy,
and will feel for any sign of uterine polyps. Depending
on the results of this examination, the doctor may
want to do more extensive testing.
GALE ENCYCLOPEDIA OF MEDICINE

It is common for women just beginning HRT to
experience some bleeding. Most women who are on
HRT also take progesterone with the estrogen and
may have monthly withdrawal bleeding. Again, this
is a normal side effect that usually does not require
treatment.
Postmenopausal bleeding due to bleeding of the
vagina or vulva can be treated with local application of
estrogen or HRT.
When diagnosis indicates cancer, some form of
surgery is required. The uterus, cervix, ovaries, and
fallopian tubes may all be removed depending on the
type and location of the cancer. If the problem is
estrogen- or androgen-producing tumors elsewhere
in the body, these must also be surgically removed.
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Postmenopausal bleeding

the vagina may occur because when estrogen secretion
stops, the vagina dries out and can diminish (atrophy).
This is the most common cause of bleeding from the
lower reproductive tract.

Postpartum depression

Resources

KEY TERMS
Dilation and curettage (D & C)—A procedure performed under anesthesia during which the cervix is
opened more (or dilated) and tissue lining the uterus
is scraped out with a metal, spoon-shaped instrument
or a suction tube. The procedure can be used to
diagnose a problem or to remove growths (polyps).
Endometrial biopsy—The removal of uterine tissue
samples either by suction or scraping; the cervix is
not dilated. The procedure has a lower rate of
diagnostic accuracy than D & C, but can be done
as an office procedure under local anesthesia.
Endometrium—The tissue lining the inside of the
uterus.
Fibroid tumors—Non-cancerous (benign) growths
in the uterus. These growths occur in 30–40% of
women over age 40, and do not need to be
removed unless they are causing symptoms that
interfere with a woman’s normal activities.
Osteoporosis—The excessive loss of calcium from
the bones, causing the bones to become fragile and
break easily. Postmenopausal women are especially vulnerable to this condition because estrogen, a hormone that protects bones against calcium
loss, decreases drastically after menopause.

Postmenopausal bleeding that is not due to cancer and
cannot be controlled by any other treatment usually
requires a hysterectomy.

Prognosis
Response to treatment for postmenopausal bleeding is highly individual and is not easy to predict. The
outcome depends largely on the reason for the bleeding. Many women are successfully treated with hormones. As a last resort, hysterectomy removes the
source of the problem by removing the uterus.
However, this operation is not without risk and the
possibility of complications. The prognosis for women
who have various kinds of reproductive cancer varies
with the type of cancer and the stage at which the
cancer is diagnosed.

Prevention
Postmenopausal bleeding is not a preventable disorder. However, maintaining a healthy weight will
decrease the chances of it occurring.
2994

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345.
<http://www.cancer.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Tish Davidson, A.M.

Postpartum blues see Postpartum depression

Postpartum depression
Definition
Postpartum depression is a mood disorder that
begins after childbirth and usually lasts beyond six
weeks.

Description
The onset of postpartum depression tends to be
gradual and may persist for many months, or develop
into a second bout following a subsequent pregnancy.
Postpartum depression affects approximately 15% of
all childbearing women. Mild to moderate cases are
sometimes unrecognized by women themselves. Many
women feel ashamed if they are not coping and so may
conceal their difficulties. This is a serious problem that
disrupts women’s lives and can have effects on the
baby, other children, her partner, and other relationships. Levels of depression for fathers also increase
significantly.
Postpartum depression is often divided into two
types: early onset and late onset. An early onset most
often seems like the ‘‘blues,’’ a mild brief experience
during the first days or weeks after birth. During the
first week after the birth up to 80% of mothers will
experience the ‘‘baby blues.’’ This is usually a time of
extra sensitivity and symptoms include tearfulness,
irritability, anxiety, and mood changes, which tend
to peak between three to five days after childbirth.
The symptoms normally disappear within two weeks
without requiring specific treatment apart from understanding, support, skill, and practice. In short, some
depression, tiredness, and anxiety may fall within the
‘‘normal’’ range of reactions to giving birth.
Late onset appears several weeks after the birth.
This involves a slowly growing feeling of sadness,
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
As of 2006, experts cannot say what causes postpartum depression. Most likely, it is caused by many
factors that vary from individual to individual.
Mothers commonly experience some degree of depression during the first weeks after birth. Pregnancy and
birth are accompanied by sudden hormonal changes
that affect emotions. Additionally, the 24-hour
responsibility for a newborn infant represents a
major psychological and lifestyle adjustment for
most mothers, even after the first child. These physical
and emotional stresses are usually accompanied by
inadequate rest until the baby’s routine stabilizes, so
fatigue and depression are not unusual.
Experiences vary considerably but usually include
several symptoms.
Feelings:


persistent low mood



inadequacy, failure, hopelessness, helplessness



exhaustion, emptiness, sadness, tearfulness



guilt, shame, worthlessness



confusion, anxiety, and panic



fear for the baby and of the baby



fear of being alone or going out
Behaviors:



lack of interest or pleasure in usual activities



insomnia or excessive sleep, nightmares



not eating or overeating



decreased energy and motivation



withdrawal from social contact



poor self-care



inability to cope with routine tasks
Thoughts:



inability to think clearly and make decisions



lack of concentration and poor memory



running away from everything



fear of being rejected by partner



worry about harm or death to partner or baby



ideas about suicide

GALE ENCYCLOPEDIA OF MEDICINE

Some symptoms may not indicate a severe problem. However, persistent low mood or loss of interest
or pleasure in activities, along with four other symptoms occurring together for a period of at least two
weeks, indicate clinical depression, and require adequate treatment.
There are several important risk factors for postpartum depression, including:


stress



lack of sleep



poor nutrition



lack of support from one’s partner, family or friends



family history of depression



labor/delivery complications for mother or baby



premature or postmature delivery



problems with the baby’s health



separation of mother and baby



A difficult baby (temperament, feeding, sleeping,
settling problems)



preexisting neurosis or psychosis

Diagnosis
There is no diagnostic test for postpartum depression. However, it is important to understand that it is,
nonetheless, a real illness, and like a physical ailment,
it has specific symptoms.

Treatment
Several treatment options exist, including medication, psychotherapy, counseling, and group treatment
and support strategies, depending on the woman’s
needs. One effective treatment combines antidepressant medication and psychotherapy. These types of
medication are often effective when used for 3 to 4
weeks. Any medication use must be carefully considered if the woman are breast-feeding, but with
some medications, continuing breast-feeding is safe.
Nevertheless, medication alone is never sufficient and
should always be accompanied by counseling or other
support services.

Alternative treatment
Postpartum depression can be effectively alleviated through counseling and support groups, so
that the mother doesn’t feel she is alone in her feelings.
Constitutional homeopathy can be the most effective
treatment of the alternative therapies because it acts
2995

Postpartum depression

depression, lack of energy, chronic tiredness, inability
to sleep, change in appetite, significant weight loss or
gain, and difficulty caring for the baby.

Postpolio syndrome

on the emotional level where postpartum depression is
felt. Acupuncture, Chinese herbs, and Western herbs
can all help the mother suffering from postpartum
depression come back to a state of balance. Seeking
help from a practitioner allows the new mother to feel
supported and cared for and allows for more effective
treatment.
A new mother also should remember that this
time of stress does not last forever. In addition, there
are useful things she can do for herself, including:


valuing her role as a mother and trusting her own
judgment



making each day as simple as possible



avoiding extra pressures or unnecessary tasks



trying to involve her partner more in the care of the
baby from the beginning



discussing with her partner how both can share the
household chores and responsibilities



scheduling frequent outings, such as walks and short
visits with friends



having the baby sleep in a separate room so she
sleeps more restfully



sharing her feelings with her partner or a friend who
is a good listener



talking with other mothers to help keep problems in
perspective



trying to sleep or rest when the baby is sleeping



taking care of her health and well-being.



not losing her sense of humor

Prognosis
With support from friends and family, mild postpartum depression usually disappears quickly. If
depression becomes severe, a mother cannot care for
herself and the baby, and in rare cases, hospitalization
may be necessary. Yet, medication, counseling, and
support from others usually cures even severe depression in 3–6 months.

Prevention
Exercise can help enhance a new mother’s emotional well-being. New mothers should also try to
cultivate good sleeping habits and learn to rest when
they feel physically or emotionally tired. It’s important
for a woman to learn to recognize her own warning
signs of fatigue, respond to them by taking a break.
2996

Resources
ORGANIZATIONS

Depression After Delivery (D.A.D.). P.O. Box 1282,
Morrisville, PA 19067. (800) 944-4773.
Postpartum Support International. 927 North Kellog Ave.,
Santa Barbara, CA 93111. (805) 967-7636.

David James Doermann

Postpartum psychosis see Postpartum
depression

Postpolio syndrome
Definition
Postpolio syndrome (PPS) is a condition that
strikes survivors of the disease polio. PPS occurs
about 20–30 years after the original bout with polio,
and causes slow but progressive weakening of muscles.

Description
Polio is a disease caused by the poliovirus. It most
commonly infects younger children, although it can
also infect older children and adults. About 90% of
people infected by poliovirus develop only a mild case
or no illness at all. However, infected people can continue to spread the virus to others. In its most severe
form polio causes paralysis of the muscles of the legs,
arms, and respiratory system.
About 1% of all people infected with poliovirus
develop the actual disease known as polio. In these
cases, the virus (which enters the person’s body
through the mouth) multiplies rapidly within the intestine. The viruses then invade the nearby lymphatic
system. Eventually, poliovirus enters the bloodstream,
which allows it to gain access to the central nervous
system or CNS (the brain and spinal cord). The virus
may actually infect a nerve elsewhere in the body, and
then spread along that nerve to enter the brain.
The major illness associated with poliovirus often
follows a mild illness, which has symptoms of fever,
nausea, and vomiting. However, after a symptom-free
interval of several days, the patient who is on the way
to a major illness develops new symptoms such as
headache and back and neck pain. These symptoms
are due to invasion of the nervous system. The motor
nerves (those nerves responsible for movement of the
muscles) become inflamed, injured, and destroyed.
The muscles, therefore, no longer receive any messages
GALE ENCYCLOPEDIA OF MEDICINE

The maximum state of paralysis is usually reached
within just a few days. The remaining, unaffected
nerves then begin the process of attempting to grow
branches to compensate (make up for) the destroyed
nerves. This process continues for about six months.
Whatever function has not been regained in this
amount of time will usually be permanently lost.

Causes and symptoms
PPS occurs in about 25% of patients, several decades after their original infection with polio. However,
long-term follow-up indicates that two thirds of polio
survivors may experience new weakness. Several theories exist as to the cause of this syndrome.
One such theory has looked at the way function is
regained by polio survivors. Three mechanisms seem
to be at work:


injured nerves recuperate and begin functioning
again



muscles that still have working nerve connections
grow in size and strength, in order to take over for
other paralyzed muscles



working nerves begin to send small branches out to
muscles whose original nerves were destroyed by
polio

As a person ages, injured nerves that were able to
regain function may fail again, as may muscles that
have been over-worked for years in order to compensate for other paralyzed muscles. Even the uninjured
nerves that provided new nerve twigs to the muscles
may begin to falter after years of relative over-activity.
This theory, then, suggests that the body’s ability to
compensate for destroyed nerves may eventually begin
to fail. The compensating nerves and muscles grow
older, and because they’ve been working so much
harder over the years, they wear out relatively sooner
than would be expected of normal nerves and muscles.
Some researchers look at this situation as a form of
premature aging, brought on by overuse.
Other researchers note that normal aging includes
the loss of a fair number of motor nerves. When a
patient has already lost motor nerves through polio,
normal loss of motor nerves through aging may cause
GALE ENCYCLOPEDIA OF MEDICINE

the number of remaining working nerves to drop low
enough to cause symptoms of weakness.
Other theories of PPS include the possibility that
particles of the original polioviruses remain in the
body. These particles may exert a negative effect,
decades later, or they may cause the body’s immune
system to produce substances originally intended to
fight the invading virus, but which may accidentally
set off a variety of reactions within the body that
actually serve to interfere with the normal functioning
of the nerves and muscles.
Still other researchers are looking at the possibility that polio patients have important spinal cord
changes which, over time, affect the nerves responsible
for movement.
The symptoms of PPS include generalized fatigue,
low energy, progressively increasing muscle weakness,
shrinking muscle size (atrophy), involuntary twitching
of the muscle fibers (fasciculations), painful muscles
and joints, difficulties with breathing and swallowing,
and sleep problems.
Survivors of polio may also develop arthritis of the
spine, shoulders, or arms, related to the long-term use
of crutches or overcompensation for weak leg muscles.

Diagnosis
Diagnosis is primarily through history. When a
patient who has recovered from polio some decades
previously begins to experience muscle weakness, PPS
must be strongly suspected.

Treatment
Just as there are no treatments available to reverse
the original damage of polio, there are also no treatments available to reverse the damaging effects of post
polio syndrome. Attempts can be made to relieve some
of the symptoms, however.
Pain and inflammation of the muscles and joints
can be treated with anti-inflammatory medications,
application of hot packs, stretching exercises, and
physical therapy. Exercises to maintain/increase flexibility are particularly important. However, an exercise regimen must be carefully designed, so as not to
strain already fatigued muscles and nerves.
Some patients will require new types of braces to
provide support for weakening muscles. Others will
need to use wheelchairs or motorized scooters to maintain mobility.
Sleep problems and respiratory difficulties may be
related to each other. If breathing is labored during
2997

Postpolio syndrome

from the brain or spinal cord. The muscles become
weak, floppy, and then totally paralyzed (unable to
move). All muscle tone is lost in the affected limb, and
the muscle begins to decrease in size (atrophy). The
affected muscles are often only on one side (asymmetric paralysis) of the body. Sensation (the person’s
ability to feel) is not affected in these paralyzed limbs.

Prader-Willi syndrome

Postural drainage see Chest physical therapy

KEY TERMS
Asymmetric—Not occurring equally on both sides
of the body.
Atrophy—Shrinking, growing smaller in size.
Flaccid—Weak, soft, floppy.
Paralysis—The inability to voluntarily move.

Postural hypotension see Orthostatic
hypotension
Postviral thrombocytopenia see Idiopathic
thrombocytopenic purpura
Potassium hydroxide test see KOH test
Potassium imbalance see Hyperkalemia;
Hypokalemia

sleep, the blood’s oxygen content may drop low
enough to interfere with the quality of sleep. This
may require oxygen supplementation, or even the use
of a machine to aid in breathing.

Prognosis

Prader-Willi syndrome

Prognosis for patients with post polio syndrome is
relatively good. It is a very slow, gradually progressing
syndrome. Only about 20% of all patients with PPS
will need to rely on new aids for mobility or breathing.
It appears that the PPS symptoms reach their most
severe about 30–34 years after original diagnosis of
polio.

Prevention
There is no way to prevent PPS. However, paying
attention to what types of exertion worsen symptoms
may slow the progression of the syndrome.

Definition
Prader-Willi syndrome (PWS) is a genetic condition caused by the absence of chromosomal material
from chromosome 15. The genetic basis of PWS is
complex. Characteristics of the syndrome include
developmental delay, poor muscle tone, short stature,
small hands and feet, incomplete sexual development,
and unique facial features. Insatiable appetite is a
classic feature of PWS. This uncontrollable appetite
can lead to health problems and behavior
disturbances.

Description

Resources
ORGANIZATIONS

International Polio Network. 4207 Lindell Blvd., Suite 110,
St. Louis, MO 63108-2915. (314) 534-0475.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914) 4287100. resourcecenter@modimes.org. <http://
www.modimes.org>.
Polio Survivors Association. 12720 Lareina Ave., Downey,
CA 90242. (310) 862-4508.

Rosalyn Carson-DeWitt, MD

Postpoliomyelitis muscular atrophy see
Postpolio syndrome
Postpoliomyelitis syndrome see Postpolio
syndrome
Poststreptococcal glomerulonephritis see
Acute poststreptococcal
glomerulonephritis
2998

PPD skin test see Tuberculin skin test

The first patients with features of PWS were
described by Dr. Prader, Dr. Willi, and Dr. Lambert
in 1956. Since that time, the complex genetic basis of
PWS has begun to be understood. Initially, scientists
found that individuals with PWS have a portion of
genetic material deleted (erased) from chromosome
15. In order to have PWS, the genetic material must
be deleted from the chromosome 15 received from
one’s father. If the deletion is on the chromosome 15
inherited from one’s mother a different syndrome
develops. This was an important discovery. It demonstrated for the first time that the genes inherited from
one’s mother can be expressed differently than the
genes inherited from one’s father.
Over time, scientists realized that some individuals with PWS do not have genetic material deleted
from chromosome 15. Further studies found that
these patients inherit both copies of chromosome 15
from their mother. This is not typical. Normally, an
individual receives one chromosome 15 from their
father and one chromosome 15 from their mother.
GALE ENCYCLOPEDIA OF MEDICINE

characteristics. Each pair is assigned a number or a
letter. When viewed under a microscope, chromosomes within the same pair appear identical because
they contain the same genes.

Scientists are still discovering other causes of
PWS. A small number of patients with PWS have a
change (mutation) in the genetic material on the chromosome 15 inherited from their father. This mutation
prevents certain genes on chromosome 15 from working properly. PWS develops when these genes do not
work normally.

Most chromosomes have a constriction near the
center called the centromere. The centromere separates the chromosome into long and short arms. The
short arm of a chromosome is called the ‘‘p arm.’’ the
long arm and is called the ‘‘q arm,’’

Newborns with PWS generally have poor muscle
tone, (hypotonia) and do not feed well. This can lead
to poor weight gain and failure to thrive. Genitalia
can be smaller than normal. Hands and feet are also
typically smaller than normal. Some patients with
PWS have unique facial characteristics. These unique
facial features are typically subtle and detectable only
by physicians.
As children with PWS age, development is typically slower than normal. Developmental milestones,
such as crawling, walking and talking occur later than
usual. Developmental delay continues into adulthood
for approximately 50% of individuals with PWS. At
about one to two years of age, children with PWS
develop an uncontrollable, insatiable appetite. Left
to their own devices, individuals with PWS will eat
until they suffer from life-threatening obesity. The
desire to eat can lead to significant behavior problems.
The symptoms and features of PWS require life
long support and care. If food intake is strictly monitored and various therapies provided, individuals
with PWS have a normal life expectancy.
PWS affects approximately 1 in 10,000 to 25,000
live births. It is the most common genetic cause of lifethreatening obesity. It affects both males and females.
PWS can be seen in all races and ethnic groups.

Causes and symptoms
In order to comprehend the various causes of
PWS, the nature of chromosomes and genes must be
well understood. Human beings have 46 chromosomes
in the cells of their body. Chromosomes contain genes,
which regulate the function and development of the
body. An individual’s chromosomes are inherited
from his/her parents. Each parent normally gives a
child 23 chromosomes. A child receives 23 chromosomes from the egg and 23 chromosomes from the
sperm.
The 46 chromosomes in the human body are
divided into pairs based on their physical
GALE ENCYCLOPEDIA OF MEDICINE

Chromosomes in the same pair contain the same
genes. However, some genes work differently depending on if they were inherited from the egg or the sperm.
Sometimes, genes are silenced when inherited from the
mother. Other times, genes are silenced when inherited
from the father. When genes in a certain region on a
chromosome are silenced, they are said to be
‘‘imprinted.’’ Imprinting is a normal process that
does not typically cause disease. If normal imprinting
is disrupted a genetic disease can develop.
Individuals have two complete copies of chromosome 15. One chromosome 15 is inherited from the
mother, or ‘‘maternal’’ in origin. The other chromosome 15 is inherited from the father, or is ‘‘paternal’’ in
origin.
Chromosome 15 contains many different genes.
There are several genes found on the q arm of chromosome 15 that are imprinted. A gene called ‘‘SNPRN’’
is an example of one of these genes. It is normally
imprinted, or silenced, if inherited from the mother.
The imprinting of this group of maternal genes does
not typically cause disease. The genes in this region
should not be imprinted if paternal in origin. Normal
development depends on these paternal genes being
present and active. If these genes are deleted, not
inherited, or incorrectly imprinted PWS develops.
Seventy percent of the cases of PWS are caused
when a piece of material is deleted, or erased, from the
paternal chromosome 15. This deletion occurs in a
specific region on the q arm of chromosome 15. The
piece of chromosomal material that is deleted contains
genes that must be present for normal development.
These paternal genes must be working normally,
because the same genes on the chromosome 15 inherited from the mother are imprinted. When these paternal genes are missing, the brain and other parts of the
body do not develop as expected. This is what causes
the symptoms associated with PWS.
In 99% of the cases of PWS the deletion is sporadic. This means that it happens randomly and there is
not an apparent cause. It does not run in the family. If
a child has PWS due to a sporadic deletion in the
paternal chromosome 15, the chance the parents
2999

Prader-Willi syndrome

When a person receives both chromosomes from the
same parent it is called ‘‘uniparental disomy’’. ‘‘When
a person receives both chromosomes from his or her
mother it is called ‘‘maternal uniparental disomy.’’

Prader-Willi syndrome

could have another child with PWS is less than 1%. In
fewer than 1% of the cases of PWS there is a chromosomal rearrangement in the family which causes the
deletion. This chromosomal rearrangement is called a
‘‘translocation.’’ If a parent has a translocation the
risk of having a child with PWS is higher than 1%.
PWS can also develop if a child receives both chromosome 15s from his/her mother. This is seen in
approximately 25% of the cases of PWS. ‘‘Maternal
uniparental disomy’’. Maternal uniparental disomy for
chromosome 15 leads to PWS because the genes on
chromosome 15 that should have been inherited from
the father are missing, and the genes on both the chromosome 15s inherited from the mother are imprinted.
PWS caused by maternal uniparental is sporadic.
This means that it occurs randomly and there is not an
apparent cause. If a child has PWS due to maternal
uniparental disomy the chance the parents could have
another child with PWS is less than 1%.
Approximately 3–4% of patients with PWS have
a change (mutation) in a gene located on the q arm of
chromosome 15. This mutation leads to incorrect
imprinting. This mutation causes genes inherited
from the father to be imprinted or silenced, which
should not normally be imprinted. If a child has
PWS due to a mutation that changes imprinting, the
chance the parents could have another child with PWS
is approximately 5%.
Infants with PWS have weak muscle tone (hypotonia). This hypotonia causes problems with sucking
and eating. Infants with PWS may have problems
gaining weight. Some infants with PWS are diagnosed
with ‘‘failure to thrive’’ due to slow growth and development. During infancy, babies with PWS may also
sleep more than normal and have problems controlling their temperature.
Some of the unique physical features associated
with PWS can be seen during infancy. Genitalia that is
smaller than normal is common. This may be more
evident in males with PWS. Hands and feet may also
be smaller than average. The unique facial features
seen in some patients with PWS may be difficult to
detect in infancy. These facial features are very mild
and do not cause physical problems.
As early as six months, but more commonly at one
to two years a compulsive desire to eat develops. This
uncontrollable appetite is a classic feature of PWS.
Individuals with PWS lack the ability to feel full or
satiated. This uncontrollable desire to eat is thought
to be related to a difference in the brain, which controls
hunger. Over-eating (hyperpahgia), a lack of a desire to
exercise, and a slow metabolism places individuals with
3000

PWS at high risk for severe obesity. Some individuals
with PWS may also have a reduced ability to vomit.
Behavior problems are a common feature of PWS.
Some behavior problems develop from the desire to
eat. Other reported problems include obsessive/compulsive behaviors, depression, and temper tantrums.
Individuals with PWS may also pick their own skin
(skin picking). This unusual behavior may be due to a
reduced pain threshold.
Developmental delay, learning disabilities, and
mental retardation are associated with PWS.
Approximately 50% of individuals with PWS have
developmental delay. The remaining 50% are
described as having mild mental retardation. The mental retardation can occasionally be more severe.
Infants and children with PWS are often delayed in
development.
Puberty may occur early or late, but it is usually
incomplete. In addition to the effects on sexual development and fertility, individuals do not undergo the
normal adolescent growth spurt and may be short as
adults. Muscles often remain underdeveloped and
body fat is increased.

Diagnosis
During infancy the diagnosis of PWS may be
suspected if poor muscle tone, feeding problems,
small genitalia, or the unique facial features are present. If an infant has these features, testing for PWS
should be performed. This testing should also be
offered to children and adults who display features
commonly seen in PWS (developmental delay,
uncontrollable appetite, small genitalia, etc.). There
are several different genetic tests that can detect
PWS. All of these tests can be performed from a
blood sample.
Methylation testing detects 99% of the cases of
PWS. Methylation testing can detect the absence of
the paternal genes that should be normally active on
chromosome 15. Although methylation testing can
accurately diagnose PWS, it can not determine if the
PWS is caused by a deletion, maternal uniparental
disomy, or a mutation that disrupts imprinting. This
information is important for genetic counseling.
Therefore, additional testing should be performed.
Chromosome analysis can determine if the PWS is
the result of a deletion in the q arm of chromosome 15.
Chromosome analysis, also called ‘‘karyotyping,’’
involves staining the chromosomes and examining
them under a microscope. In some cases the deletion
of material from chromosome 15 can be easily seen. In
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

More specialized DNA testing is required to
detect maternal uniparental disomy or a mutation
that disrupts imprinting. This DNA testing identifies
unique DNA patterns in the mother and father. The
unique DNA patterns are then compared with the
DNA from the child with PWS.

Amniocentesis—A procedure in which a needle is
inserted through a pregnant woman’s abdomen
and into her uterus. Amniotic fluid is then removed
from around the fetus and may be used for genetic
testing.

PWS can be detected before birth if the mother
undergoes amniocentesis testing or chorionic villus
sampling (CVS). This testing is only recommended if
the mother or father is known to have a chromosome
rearrangement, or if they already have a child with
PWS syndrome.

Deletion—Removal of a piece of genetic material.
DNA—Deoxyribonucleic acid. Genes are made of
sections of DNA.

Treatment
There is currently not a cure for PWS. Treatment
during infancy includes therapies to improve muscle
tone. Some infants with PWS also require special nipples and feeding techniques to improve weight gain.
Treatment and management during childhood,
adolescence, and adulthood is typically focused on
weight control. Strict control of food intake is vital to
prevent severe obesity. In many cases food must be
made inaccessible. This may involve unconventional
measures such as locking the refrigerator or kitchen
cabinets. A lifelong restricted-calorie diet and regular
exercise program are also suggested. Unfortunately,
diet medications have not been shown to significantly
prevent obesity in PWS. However, growth hormone
therapy has been shown to improve the poor muscle
tone and reduced height typically associated with PWS.
Special education may be helpful in treating developmental delays and behavior problems. Individuals
with PWS typically excel in highly structured
environments.

Centromere—Major constriction in a chromosome.

FISH—(flourescence in-situ hybridization) Technique used to detect small deletions or rearrangements in chromosomes.
Gene—Segment of DNA that controls the development and function of the body. Genes are contained within chromosomes.
Hyperphagia—Over-eating.
Hypotonia—Low muscle tone.
Imprinting—Process that silences a gene or group
of genes. The genes are silenced depending on if
they are inherited through the egg or the sperm.
Maternal—From one’s mother.
Maternal uniparental disomy—Chromosome
abnormality in which both chromosomes in a pair
are inherited from one’s mother.
Methylation testing—DNA testing that detects if a
gene is active or imprinted.
Mutation—A change in a gene.
Paternal—From one’s father.
Translocation—Chromosome abnormality in which
chromosomes are rearranged and placed together.
Uniparental disomy—Chromosome abnormality
in which both chromosomes in a pair are inherited
from the same parent.

Prognosis
Life expectancy is normal and the prognosis good,
if weight gain is well controlled.
Resources
BOOKS

Couch, Cheryl. My Rag Doll. Couch Publishing, October
2000.
PERIODICALS

Butler, Merlin G. and Travis Thompson. ‘‘PraderWilliSyndrome: Clinical and Genetic Findings.’’ The
Endocrinologist 10 (2000): 3S–16S.
GALE ENCYCLOPEDIA OF MEDICINE

State, Matthew W., and Elisabeth Dykens. ‘‘Genetics of
Childhood Disorders: XV. Prader-Willi Syndrome:
Genes, Brain and Behavior.’’ J. Am. Acad. Child.
Adolesc. Psychiatry 39, no. 6 (June 2000): 797–800.
ORGANIZATIONS

Alliance of Genetic Support Groups. 4301 Connecticut Ave.
NW, Suite 404, Washington DC 20008. (202) 966-5557.
Fax: (202) 966-8553. <http://
www.geneticalliance.org>.
International Prader-Willi Syndrome Organization.
<http://www.ipwsp.org>.
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Prader-Willi syndrome

other cases, further testing must be performed. FISH
(fluorescence in-situ hybridization) is a special technique that detects small deletions that cause PWS.

Precocious puberty

National Organization for Rare Disorders, Inc. P.O. Box
8923, New Fairfield, CT 06812. (800) 999-6673.
<http://www.rarediseases.org>.
Prader-Willi Foundation. 223 Main Street, Port
Washington, NY 11050. (800)253- 7993.
<http://www.prader-willi.org>.
Prader-Willi Syndrome Association (USA). 5700 Midnight
Pass Rd., Sarasota, FL 34242. (800)926-4797.
<http://www.pwsusa.org>.

Causes and symptoms

OTHER

Gene Clinics. <http://www.geneclinics.org/profiles/
pws/details.html>.
OMIM. <http://www.ncbi.nlm.nih.gov/htbin-port/
Omim/dispmim?176270>.

Holly Ann Ishmael, M.S.

Praziquantel see Antihelminthic drugs

Precocious puberty
Definition
Sexual development before the age of eight in
girls, and age 10 in boys.

Description
Not every child reaches puberty at the same time,
but in most cases it’s safe to predict that sexual development will begin at about age 11 in girls and 12 or 13 in
boys. However, occasionally a child begins to develop
sexually much earlier. Between four to eight times more
common in girls than boys, precocious puberty occurs
in one out of every 5,000 to 10,000 U.S. children.
Precocious puberty often begins before age 8 in
girls, triggering the development of breasts and hair
under the arms and in the genital region. The onset of
ovulation and menstruation also may occur. In boys,
the condition triggers the development of a large penis
and testicles, with spontaneous erections and the production of sperm. Hair grows on the face, under arms
and in the pubic area, and acne may become a problem.
While the early onset of puberty may seem fairly
benign, in fact it can cause problems when hormones
trigger changes in the growth pattern, essentially halting growth before the child has reached normal adult
height. Girls may never grow above 5 ft (152 cm) and
boys often stop growing by about 5 ft 2 in (157 cm).
The abnormal growth patterns are not the only
problem, however. Children with this condition look
3002

noticeably different than their peers, and may feel
rejected by their friends and socially isolated. Adults
may expect these children to act more maturely simply
because they look so much older. As a result, many of
these children–especially boys–are much more aggressive than others their own age, leading to behavior
problems both at home and at school.

Puberty begins when the brain secretes a hormone
that triggers the pituitary gland to release gonadotropins, which in turn stimulate the ovaries or testes to
produce sex hormones. These sex hormones (especially estrogen in girls and testosterone in boys) are
what causes the onset of sexual maturity.
The hormonal changes of precious puberty are
normal–it’s just that the whole process begins a few
years too soon. Especially in girls, there is not usually
any underlying problem that causes the process to
begin too soon. However, some boys do inherit the
condition; the responsible gene may be passed directly
from father to son, or inherited indirectly from the
maternal grandfather through the mother, who does
not begin early puberty herself. This genetic condition
in girls can be traced in only about 1% of cases.
In about 15% of cases, there is an underlying
cause for the precocious puberty, and it is important
to search for these causes. The condition may result
from a benign tumor in the part of the brain that
releases hormones. Less commonly, it may be caused
by other types of brain tumors, central nervous system
disorders, or adrenal gland problems.

Diagnosis
Physical exams can reveal the development of
sexual characteristics in a young child. Bone x rays
can reveal bone age, and pelvic ultrasound may show
an enlarged uterus and rule out ovarian or adrenal
tumors. Blood tests can highlight higher-than-normal
levels of hormones. MRI or CAT scans should be
considered to rule out intracranial tumors.

Treatment
Treatment aims to halt or reverse sexual development so as to stop the accompanying rapid growth
that will limit a child’s height. There are two possible
approaches: either treat the underlying condition
(such as an ovarian or intracranial tumor) or change
the hormonal balance to stop sexual development. It
may not be possible to treat the underlying condition;
GALE ENCYCLOPEDIA OF MEDICINE

There are several drugs that have been developed
to do this:


histrelin (Supprelin)



nafarelin (Synarel)



synthetic gonadotropin-releasing hormone agonist



deslorelin



ethylamide



triptorelin



leuprolide

Prognosis

numbers represent two measurements, the systolic
pressure and the diastolic pressure. The systolic pressure (the first number in the example; 110/70 mm Hg)
measures the peak pressure of the blood against the
artery walls. This higher pressure occurs as blood is
being pumped out of the heart and into the circulatory system. The pumping chambers of the heart
(ventricles) squeeze to force the blood out of the
heart. The diastolic pressure (the second number in
the example 110/70 mm Hg) measures the pressure,
during the filling of the ventricles. At this point, the
atria contract to fill the ventricles. Because the ventricles are relatively relaaxed, and are not pumping
blood into the arteries, pressure in the arteries is
lower as well.

Drug treatments can slow growth to 2–3 in (5–7.5
cm) a year, allowing these children to reach normal
adult height, although the long-term effects aren’t
known.

High blood pressure in pregnancy (hypertension)
is a very serious complication. It puts both the mother
and the fetus (developing baby) at risk for a number of
problems. Hypertension can exist in several different
forms:

Resources



The preeclampsia-eclampsia continuum (also called
pregnancy-induced hypertension or PIH). In this
type of hypertension, high blood pressure is first
noted sometime after week 20 of pregnancy and is
accompanied by protein in the urine and swelling.



Chronic hypertension. This type of hypertension
usually exists before pregnancy or may develop
before week 20 of pregnancy.



Chronic hypertension with superimposed preeclampsia. This syndrome occurs when a woman
with pre-existing chronic hypertension begins to
have protein in the urine after week 20 of pregnancy.



Late hypertension. This is a form of high blood
pressure occurring after week 20 of pregnancy and
is unaccompanied by protein in the urine and does
not progress the way preeclampsia-eclampsia does.

ORGANIZATIONS

National Institute of Child Health and Human
Development. Bldg 31, Room 2A32, MSC 2425, 31
Center Drive, Bethesda, MD 20892-2425. (800) 5052742. <http://www.nichd.nih.gov/sids/sids.htm>.

Carol A. Turkington

Prednis see Corticosteroids

Preeclampsia and eclampsia
Definition
Preeclampsia and eclampsia are complications of
pregnancy. In preeclampsia, the woman has dangerously high blood pressure, swelling, and protein in the
urine. If allowed to progress, this syndrome will lead to
eclampsia.

Description
Blood pressure is a measurement of the pressure
of blood on the walls of blood vessels called arteries.
The arteries deliver blood from the heart to all of the
tissues in the body. Blood pressure is reported as two
numbers. For example, a normal blood pressure is
reported as 110/70 mm Hg (read as 110 over 70 millimeters of mercury; or just 110 over 70). These two
GALE ENCYCLOPEDIA OF MEDICINE

Preeclampsia is most common among women
who have never given birth to a baby (called nulliparas). About 7% of all nulliparas develop preeclampsia. The disease is most common in mothers
under the age of 20, or over the age of 35. AfricanAmerican women have higher rates of preeclampsia
than do Caucasian women. Other risk factors include
poverty, multiple pregnancies (twins, triplets, etc.),
pre-existing chronic hypertension or kidney disease,
diabetes, excess amniotic fluid, and a condition of the
fetus called nonimmune hydrops. The tendency to
develop preeclampsia appears to run in families.
The daughters and sisters of women who have had
preeclampsia are more likely to develop the
condition.
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Preeclampsia and eclampsia

for this reason, treatment is usually aimed at adjusting
hormone levels.

Preeclampsia and eclampsia

Causes and symptoms
Experts are still trying to understand the exact
causes of preeclampsia and eclampsia. It is generally
accepted that preeclampsia and eclampsia are problematic because these conditions cause blood vessels to
leak. The effects are seen throughout the body.


General body tissues. When blood vessels leak, they
allow fluid to flow out into the tissues of the body.
The result is swelling in the hands, feet, legs, arms,
and face. While many pregnant women experience
swelling in their feet, and sometimes in their hands,
swelling of the upper limbs and face is a sign of a
more serious problem. As fluid is retained in these
tissues, the woman may experience significant weight
gain (two or more pounds per week).



Brain. Leaky vessels can cause damage within the
brain, resulting in seizures or coma.



Eyes. The woman may experience problems seeing,
and may have blurry vision or may see spots. The
retina may become detached.



Lungs. Fluid may leak into the tissues of the lungs,
resulting in shortness of breath.



Liver. Leaky vessels within the liver may cause it to
swell. The liver may be involved in a serious complication of preeclampsia, called the HELLP syndrome.
In this syndrome, red blood cells are abnormally
destroyed, chemicals called liver enzymes are abnormally high, and cells involved in the clotting of blood
(platelets) are low.



Kidneys. The small capillaries within the kidneys
can leak. Normally, the filtration system within
the kidney is too fine to allow protein (which is
relatively large) to leave the bloodstream and enter
the urine. In preeclampsia, however, the leaky capillaries allow protein to be dumped into the urine.
The development of protein in the urine is very
serious, and often results in a low birth weight
baby. These babies have a higher risk of complications, including death.



Blood pressure. In preeclampsia, the volume of circulating blood is lower than normal because fluid is
leaking into other parts of the body. The heart tries
to make up for this by pumping a larger quantity of
blood with each contraction. Blood vessels usually
expand in diameter (dilate) in this situation to
decrease the work load on the heart. In preeclampsia,
however, the blood vessels are abnormally constricted, causing the heart to work even harder to
pump against the small diameters of the vessels.
This causes an increase in blood pressure.

3004

The most serious consequences of preeclampsia
and eclampsia include brain damage in the mother
due to brain swelling and oxygen deprivation during
seizures. Mothers can also experience blindness, kidney failure, liver rupture, and placental abruption.
Babies born to preeclamptic mothers are often smaller
than normal, which makes them more susceptible to
complications during labor, delivery, and in early
infancy. Babies of preeclamptic mothers are also at
risk of being born prematurely, and can suffer the
complications associated with prematurity.

Diagnosis
Diagnosing preeclampsia may be accomplished
by noting painless swelling of the arms, legs, and/or
face, in addition to abnormal weight gain. The
patient’s blood pressure is taken during every doctor’s
visit during pregnancy. An increase of 30 mm Hg in
the systolic pressure, or 15 mm Hg in the diastolic
pressure, or a blood pressure reading greater than
140/90 mm Hg is considered indicative of preeclampsia. A simple laboratory test in the doctor’s office can
indicate the presence of protein in a urine sample (a
dipstick test). A more exact measurement of the
amount of protein in the urine can be obtained by
collecting urine for 24 hours, and then testing it in a
laboratory to determine the actual quantity of protein
present. A 24-hour urine specimen containing more
than 500 mg of protein is considered indicative of
preeclampsia.

Treatment
With mild preeclampsia, treatment may be limited
to bed rest, with careful daily monitoring of weight,
blood pressure, and urine protein via dipstick. This
careful monitoring will be required throughout pregnancy, labor, delivery, and even for 2–4 days after the
baby has been born. About 25% of all cases of eclampsia develop in the first few days after the baby’s birth.
If the diastolic pressure does not rise over 100 mm Hg
prior to delivery, and no other symptoms develop, the
woman can continue pregnancy until the fetus is
mature enough to be delivered safely. Ultrasound
tests can be performed to monitor the health and
development of the fetus.
If the diastolic blood pressure continues to rise
over 100 mm Hg, or if other symptoms like headache,
vision problems, abdominal pain, or blood abnormalities develop, then the patient may require medications to prevent seizures. Magnesium sulfate is
commonly given through a needle in a vein (intravenous, or IV). Medications that lower blood pressure
GALE ENCYCLOPEDIA OF MEDICINE

Capillary—The tiniest blood vessels with the smallest diameter. These vessels receive blood from the
arterioles and deliver blood to the venules.
Diastolic—The phase of blood circulation in which
the heart’s pumping chambers (ventricles) are
being filled with blood. During this phase, the ventricles are at their most relaxed, and the pressure
against the walls of the arteries is at its lowest.
Placenta—The organ that provides oxygen and
nutrition from the mother to the fetus during
pregnancy. The placenta is attached to the wall of
the uterus and leads to the fetus via the umbilical
cord.
Placental abruption—An abnormal separation of
the placenta from the uterus before the birth of the
baby, with subsequent heavy uterine bleeding.
Normally, the baby is born first and then the placenta is delivered within a half hour.
Systolic—The phase of blood circulation in which
the heart’s pumping chambers (ventricles) are
actively pumping blood. The ventricles are squeezing (contracting) forcefully, and the pressure
against the walls of the arteries is at its highest.
Urine dipstick test—A test using a small, chemically treated strip that is dipped into a urine sample;
when testing for protein, an area on the strip
changes color depending on the amount of protein
(if any) in the urine.
Uterus—The muscular organ that contains the
developing baby during pregnancy.
Ventricles—The two chambers of the heart that are
involved in pumping blood. The right ventricle
pumps blood into the lungs to receive oxygen.
The left ventricle pumps blood into the circulation
of the body to deliver oxygen to all of the body’s
organs and tissues.

(antihypertensive drugs) are reserved for patients with
very high diastolic pressures (over 110 mm Hg),
because lowering the blood pressure will decrease the
amount of blood reaching the fetus. This places the
fetus at risk for oxygen deprivation. If preeclampsia
appears to be progressing toward true eclampsia, then
medications may be given in order to start labor.
Babies can usually be delivered vaginally. After the
baby is delivered, the woman’s blood pressure and
other vital signs will usually begin to return to normal
quickly.
GALE ENCYCLOPEDIA OF MEDICINE

The prognosis in preeeclampsia and eclampsia
depends on how carefully a patient is monitored.
Very careful, consistent monitoring allows quick decisions to be made, and improves the woman’s prognosis. Still, the most common causes of death in
pregnant women are related to high blood pressure.
About 33% of all patients with preeclampsia will
have the condition again with later pregnancies.
Eclampsia occurs in about 1 out of every 200 women
with preeclampsia. If not treated, eclampsia is almost
always fatal.

Prevention
More information on how preeclampsia and
eclampsia develop is needed before recommendations
can be made on how to prevent these conditions.
Research is being done with patients in high risk
groups to see if calcium supplementation, aspirin, or
fish oil supplementation may help prevent preeclampsia. Most importantly, it is clear that careful monitoring during pregnancy is necessary to diagnose
preeclampsia early. Although even carefully monitored patients may develop preeclampsia and eclampsia, close monitoring by practitioners will help
decrease the complications of these conditions.
Resources
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th Street, S.W., P.O. Box 96920.

Rosalyn Carson-DeWitt, MD

Pregnancy-induced high blood pressure see
Preeclampsia and eclampsia

Pregnancy
Definition
The period from conception to birth. After the egg
is fertilized by a sperm and then implanted in the lining
of the uterus, it develops into the placenta and
embryo, and later into a fetus. Pregnancy usually
lasts 40 weeks, beginning from the first day of the
woman’s last menstrual period, and is divided into
three trimesters, each lasting three months.
3005

Pregnancy

Prognosis

KEY TERMS

Pregnancy

Description
Pregnancy is a state in which a woman carries a
fertilized egg inside her body. Due to technological
advances, pregnancy is increasingly occurring among
older women in the United States.
First month
At the end of the first month, the embryo is about
a third of an inch long, and its head and trunk–plus the
beginnings of arms and legs–have started to develop.
The embryo receives nutrients and eliminates waste
through the umbilical cord and placenta. By the end
of the first month, the liver and digestive system begin
to develop, and the heart starts to beat.
Second month
In this month, the heart starts to pump and the
nervous system (including the brain and spinal cord)
begins to develop. The 1 in (2.5 cm) long fetus has
a complete cartilage skeleton, which is replaced by
bone cells by month’s end. Arms, legs and all of the
major organs begin to appear. Facial features begin to
form.

Sixth month
Even though its lungs are not fully developed, a
fetus born during this month can survive with intensive care. Weighing 1–1.5 lbs (454–681 g), the fetus is
red, wrinkly, and covered with fine hair all over its
body. The fetus will grow very fast during this month
as its organs continue to develop.
Seventh month
There is a better chance that a fetus born during
this month will survive. The fetus continues to grow
rapidly, and may weigh as much as 3 lb (1.3 kg) by
now. Now the fetus can suck its thumb and look
around its watery womb with open eyes.
Eighth month
Growth continues but slows down as the baby
begins to take up most of the room inside the uterus.
Now weighing 4–5 lbs (1.8–2.3 kg) and measuring
16–18 in (40–45 cm) long, the fetus may at this time
prepare for delivery next month by moving into the
head-down position.
Ninth month

Third month
By now, the fetus has grown to 4 in (10 cm) and
weighs a little more than an ounce (28 g). Now the
major blood vessels and the roof of the mouth are
almost completed, as the face starts to take on a
more recognizably human appearance. Fingers and
toes appear. All the major organs are now beginning
to form; the kidneys are now functional and the four
chambers of the heart are complete.
Fourth month
The fetus begins to kick and swallow, although
most women still can’t feel the baby move at this point.
Now 4 oz (112 g), the fetus can hear and urinate, and
has established sleep-wake cycles. All organs are now
fully formed, although they will continue to grow for
the next five months. The fetus has skin, eyebrows,
and hair.
Fifth month
Now weighing up to a 1 lb (454 g) and measuring
8–12 in (20–30 cm), the fetus experiences rapid growth
as its internal organs continue to grow. At this point,
the mother may feel her baby move, and she can hear
the heartbeat with a stethoscope.
3006

Adding 0.5 lb (227 g) a week as the due date
approaches, the fetus drops lower into the mother’s
abdomen and prepares for the onset of labor, which
may begin any time between the 37th and 42nd week
of gestation. Most healthy babies will weigh 6–9 lb
(2.7–4 kg) at birth, and will be about 20 in. long.

Causes and symptoms
The first sign of pregnancy is usually a missed
menstrual period, although some women bleed in the
beginning. A woman’s breasts swell and may become
tender as the mammary glands prepare for eventual
breastfeeding. Nipples begin to enlarge and the veins
over the surface of the breasts become more
noticeable.
Nausea and vomiting are very common symptoms
and are usually worse in the morning and during the
first trimester of pregnancy. They are usually caused
by hormonal changes, in particular, increased levels
of progesterone. Women may feel worse when their
stomach is empty, so it is a good idea to eat several
small meals throughout the day, and to keep things
like crackers on hand to eat even before getting out of
bed in the morning.
Many women also feel extremely tired during the
early weeks. Frequent urination is common, and there
GALE ENCYCLOPEDIA OF MEDICINE

Pregnancy

9th month

Lumbar vertebrae

Uterus

6th month

3rd month

Rectum
Bladder
Vagina

Pregnancy usually lasts 40 weeks in humans, beginning from the first day of the woman’s last menstrual period, and is divided
into three trimesters. The illustration above depicts the position of the developing fetus during each trimester. (Illustration by
Electronic Illustrators Group.)

may be a creamy white discharge from the vagina.
Some women crave certain foods, and an extreme
sensitivity to smell may worsen the nausea. Weight
begins to increase.

an active baby may cause sharp pains, and lower backaches are common. More rest is needed as the woman
copes with the added stress of extra weight. Braxton
Hicks contractions may get stronger.

In the second trimester (13–28 weeks) a woman
begins to look noticeably pregnant and the enlarged
uterus is easy to feel. The nipples get bigger and darker, skin may darken, and some women may feel
flushed and warm. Appetite may increase. By the
22nd week, most women have felt the baby move.
During the second trimester, nausea and vomiting
often fade away, and the pregnant woman often feels
much better and more energetic. Heart rate increases
as does the volume of blood in the body.

At about the 36th week in a first pregnancy (later
in repeat pregnancies), the baby’s head drops down
low into the pelvis. This may relieve pressure on the
upper abdomen and the lungs, allowing a woman to
breathe more easily. However, the new position places
more pressure on the bladder.

By the third trimester (29–40 weeks), many
women begin to experience a range of common symptoms. Stretch marks may develop on abdomen,
breasts, and thighs, and a dark line may appear from
the navel to pubic hair. A thin fluid may be expressed
from the nipples. Many women feel hot, sweat easily
and often find it hard to get comfortable. Kicks from
GALE ENCYCLOPEDIA OF MEDICINE

A healthy gain for most women is between 25 and
35 pounds. Women who are overweight should gain
less; and women who are underweight should gain
more. On average, pregnant women need an additional 300 calories a day. Generally, women will gain
three to five pounds in the first three months, adding
one to two pounds a week until the baby is born. An
average, healthy full-term baby at birth weighs 7.5 lb
(3.4 kg), and the placenta and fluid together weigh
another 3.5 lb. The remaining weight that a woman
gains during pregnancy is mostly due to water
3007

Pregnancy

retention and fat stores. Her breasts, for instance, gain
about 2 lb. in weight, and she gains another 4 lb due to
the increased blood volume of pregnancy.
In addition to the typical, common symptoms of
pregnancy, some women experience other problems
that may be annoying, but which usually disappear
after delivery. Constipation may develop as a result of
food passing more slowly through the intestine.
Hemorrhoids and heartburn are fairly common during
late pregnancy. Gums may become more sensitive and
bleed more easily; eyes may dry out, making contact
lenses feel painful. Pica (a craving to eat substances
other than food) may occur. Swollen ankles and varicose veins may be a problem in the second half of
pregnancy, and chloasma may appear on the face.
Chloasma, also known as the ‘‘mask of pregnancy’’ or melasma, is caused by hormonal changes
that result in blotches of pale brown skin appearing on
the forehead, cheeks, and nose. These blotches may
merge into one dark mask. It usually fades gradually
after pregnancy, but it may become permanent or
recur with subsequent pregnancies. Some women
also find that the line running from the top to the
bottom of their abdomen darkens. This is called the
linea nigra.
While the above symptoms are all considered to
be normal, there are some symptoms that could be a
sign of a more dangerous underlying problem. A pregnant woman with any of the following signs should
contact her doctor immediately:

Home pregnancy tests are more than 97% accurate if the result is positive, and about 80% accurate if
the result is negative. If the result is negative and there
is no menstrual period within another week, the pregnancy test should be repeated. While home pregnancy
tests are very accurate, they are less accurate than a
pregnancy test conducted at a lab. For this reason,
women may want to consider having a second pregnancy test conducted at their doctor’s office to be sure
of the accuracy of the result.
Blood tests to determine pregnancy are usually
used only when a very early diagnosis of pregnancy is
needed. This more expensive test, which also looks for
hCG, can produce a result within nine to 12 days after
conception.
Once pregnancy has been confirmed, there are a
range of screening tests that can be done to screen for
birth defects, which affect about 3% of unborn children. Two tests are recommended for all pregnant
women: alpha-fetoprotein (AFP) and the triple
marker test.
Other tests are recommended for women at higher
risk for having a child with a birth defect. This would
include women over age 35, who had another child or
a close relative with a birth defect, or who have been
exposed to certain drugs or high levels of radiation.
Women with any of these risk factors may want to
consider amniocentesis, chorionic villus sampling
(CVS) or ultrasound.
Other prenatal tests



abdominal pain



rupture of the amniotic sac or leaking of fluid from
the vagina

There are a range of other prenatal tests that are
routinely performed, including:



bleeding from the vagina



PAP test



no fetal movement for 24 hours (after the fifth
month)



gestational diabetes screening test at 24–28 weeks



tests for sexually transmitted diseases



continuous headaches



urinalysis



marked, sudden swelling of eyelids, hands, or face
during the last three months



blood tests for anemia or blood type

dim or blurry vision during last three months





screening for immunity to various diseases, such as
German measles



persistent vomiting

Treatment
Diagnosis
Many women first discover they are pregnant
after a positive home pregnancy test. Pregnancy
urine tests check for the presence of human chorionic
gonadotropin (hCG), which is produced by a placenta. The newest home tests can detect pregnancy
on the day of the missed menstrual period.
3008

Prenatal care is vitally important for the health of
the unborn baby. A pregnant woman should be sure to
eat a balanced, nutritious diet of frequent, small meals.
Women should begin taking 400 mcg of folic acid
several months before becoming pregnant, as folic
acid has been shown to reduce the risk of spinal cord
defects, such as spina bifida.
GALE ENCYCLOPEDIA OF MEDICINE

Alpha-fetoprotein—A substance produced by a
fetus’ liver that can be found in the amniotic fluid
and in the mother’s blood. Abnormally high levels
of this substance suggests there may be defects in
the fetal neural tube, a structure that will include
the brain and spinal cord when completely developed. Abnormally low levels suggest the possibility
of Down’ syndrome.
Braxton Hicks’ contractions—Short, fairly painless
uterine contractions during pregnancy that may be
mistaken for labor pains. They allow the uterus to
grow and help circulate blood through the uterine
blood vessels.
Chloasma—A skin discoloration common during
pregnancy, also known as the ‘‘mask of pregnancy’’
or melasma, in which blotches of pale brown skin
appear on the face. It is usually caused by hormonal
changes. The blotches may appear in the forehead,
cheeks, and nose, and may merge into one dark
mask. It usually fades gradually after pregnancy,
but it may become permanent or recur with subsequent pregnancies. Some women may also find that
the line running from the top to the bottom of their
abdomen darkens. This is called the linea nigra.
Embryo—An unborn child during the first eight
weeks of development following conception (fertilization with sperm). For the rest of pregnancy, the
embryo is known as a fetus.
Fetus—An unborn child from the end of the eights
week after fertilization until birth.
Human chorionic gonadotropin (hCG)—A hormone produced by the placenta during pregnancy.
Placenta—The organ that develops in the uterus
during pregnancy that links the blood supplies of
the mother and baby.
Rhythm method—The oldest method of contraception with a very high failure rate, in which partners
periodically refrain from having sex during ovulation. Ovulation is predicted on the basis of a
woman’s previous menstrual cycle.
Spina bifida—A congenital defect in which part of
the vertebrae fail to develop completely, leaving a
portion of the spinal cord exposed.

No medication (not even a nonprescription drug)
should be taken except under medical supervision,
since it could pass from the mother through the placenta to the developing baby. Some drugs, called
GALE ENCYCLOPEDIA OF MEDICINE

teratogens, have been proven harmful to a fetus, but
no drug should be considered completely safe (especially during early pregnancy). Drugs taken during the
first three months of a pregnancy may interfere with
the normal formation of the baby’s organs, leading to
birth defects. Drugs taken later on in pregnancy may
slow the baby’s growth rate, or they may damage
specific fetal tissue (such as the developing teeth), or
cause preterm birth.
To have the best chance of having a healthy baby,
a pregnant woman should avoid:


smoking



alcohol



street drugs



large amounts of caffeine



artificial sweeteners
Nutrition

Women should begin following a healthy diet
even before they become pregnant. This means cutting back on high-calorie, high-fat, high-sugar
snacks, and increasing the amount of fruits, vegetables and whole grains in her diet. Once she becomes
pregnant, she should make sure to get at least six to
11 servings of breads and other whole grains, three to
five servings of vegetables, two to four servings of
fruits, four to six servings of milk and milk products,
three to four servings of meat and protein foods, and
six to eight glasses of water. She should limit caffeine
to no more than one soft drink or cup of coffee
per day.

Prognosis
Pregnancy is a natural condition that usually
causes little discomfort provided the woman takes
care of herself and gets adequate prenatal care.
Childbirth education classes for the woman and her
partner help prepare the couple for labor and delivery.

Prevention
There are many ways to avoid pregnancy. A
woman has a choice of many methods of contraception
which will prevent pregnancy, including (in order of
least to most effective):


spermicide alone



natural (rhythm) method



diaphragm or cap alone



condom alone
3009

Pregnancy

KEY TERMS

Premature ejaculation

Causes and symptoms



diaphragm with spermicide



condom with spermicide



intrauterine device (IUD)



contraceptive pill



sterilization (either a man or woman)



avoiding intercourse

Resources
ORGANIZATIONS

Healthy Mothers, Healthy Babies National Coalition. 409
12th St., Washington, DC 20024. (202) 638-5577.
National Institute of Child Health and Human
Development. 9000 Rockville Pike, Bldg. 31, Rm.
2A32, Bethesda, MD 20892. (301) 496-5133.
Positive Pregnancy and Parenting Fitness. 51 Saltrock Rd.,
Baltic, CT 06330. (203) 822-8573.
OTHER

Doulas of North America <http://www.dona.com>.
Planned Parenthood. <http://
www.plannedparenthood.org>.
Pregnancy Information. <http://www.childbirth.org>.

Debra Gordon

Pregnancy test see Human chorionic
gonadotropin pregnancy test
Preleukemia see Myelodysplastic syndrome
Premature atrial contractions see Atrial
ectopic beats
Premature birth see Prematurity

Premature ejaculation
Definition
Premature ejaculation occurs when male sexual
climax (orgasm) occurs before a man wishes it or too
quickly during intercourse to satisfy his partner.

Description
Premature ejaculation is the most commonly
reported sexual complaint of men and couples. The
highest number of complaints is among teenage,
young adult, and sexually inexperienced males.
Increased risk is associated with sexual inexperience
and lack of knowledge of normal male sexual
responses.
3010

There are several reasons why a man may ejaculate prematurely. For some men, the cause is due to an
innate reflex or psychological predisposition of the
nervous system. Sometimes it can be caused by certain
drugs, such as non-prescription cold medications.
Psychological factors, such as stress, fear, or guilt
can also play a role. Examples of psychological factors
include guilt that the sexual activity is wrong or sinful,
fear of getting caught, or stress from problems at work
or home.
In general, symptoms are when a male reaches
climax in less than two minutes or when it occurs
before the male or couple want it to occur.

Diagnosis
There are no tests used to diagnose premature
ejaculation. It is usually determined by the male
involved based on his belief that he reached orgasm
too quickly. General guidelines for premature ejaculation is if it occurs in two minutes or less, or prior to
about 15 thrusts during sexual intercourse.

Treatment
In 1966, William H. Masters and Virginia E.
Johnson published Human Sexual Response, in which
they broke the first ground in approaching this topic
from a new perspective. Their method was devised by
Dr. James Seman and has been modified subsequently
by Dr. Helen Singer Kaplan and others.
A competent and orthodox sex therapist will
spend much more time focusing on the personal than
the sexual relationship between the two people who
come for treatment. Without emotional intimacy, sexual relations are superficial and sexual problems such
as premature ejaculation are not always overcome.
With that foremost in mind, a careful plan is outlined that requires dedication, patience, and commitment by both partners. It necessarily begins by
prohibiting intercourse for an extended period of
time—at least a week, often a month. This is very
important to the man because ‘‘performance anxiety’’
is the greatest enemy of performance. If he knows he
cannot have intercourse he is able to relax and focus
on the exercises. The first stage is called ‘‘sensate
focus’’ and involves his concentration on the process
of sexual arousal and climax. He should learn to
recognize each step in the process, most particularly
the moment just before the ‘‘point of no return.’’
Ideally, this stage of treatment requires the man’s
GALE ENCYCLOPEDIA OF MEDICINE

At this point the techniques diverge. The original
‘‘squeeze technique’’ requires that the partner become
expert at squeezing the head of the penis at intervals to
prevent orgasm. The modified procedure, described by
Dr. Ruth Westheimer, calls upon the man to instruct
the partner when to stop stimulating him to give him a
chance to draw back. A series of stages follows, each
offering greater stimulation as the couple gains greater
control over his arousal. This whole process has been
called ‘‘outercourse.’’ After a period of weeks, they
will have together retrained his response and gained
satisfactory control over it. In addition, they will each
have learned much about the other’s unique sexuality
and ways to increase each other’s pleasure.
With either technique, the emphasis is on the
mutual goal of satisfactory sexual relations for both
partners.
However, the 1990s ushered in a new era in the
treatment of premature ejaculation when physicians
discovered that certain antidepression drugs had a side
effect of delaying ejaculation. Clinical studies have
shown that a class of antidepressants called selective
seratonin reuptake inhibitors (SSRIs) can be very
effective in prolonging the time to ejaculation. The
individual drugs and the average amount of time
they delay ejaculation are fluoxetine (Prozac), one to
two minutes with doses of 20–40 milligrams per day
(mg/day) and eight minutes with 60 mg/day; paroxetine (Paxil), three to 10 minutes with doses of 20–40
mg/day; and sertraline (Zoloft), two to five minutes
with doses of 50–200 mg/day.

Alternative treatment
There are several alternative products, usually
found in health food and nutrition stores, designed to
be sprayed or rubbed on the penis to delay ejaculation.
Although the products promise results, there are no
valid clinical studies to support the claims. A device
called a testicular restraint, sold through erotic mailorder magazines, sometimes helps men delay ejaculation. The Velcro-like device restrains the testicles from
their natural tendency to move during sex. Testicular
movement can cause premature ejaculation.

Prognosis
The ‘‘squeeze technique’’ has elicited a 95% success
rate, whereby the patient is able to control ejaculation.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment with SSRIs is effective in 85–90% of cases.
However, the effectiveness begins to decrease after five
weeks of daily administration. Although more studies
are needed, this suggests the SSRIs are more effective
when used on an as-needed basis.

Prevention
The best prevention is obtaining adequate information on normal sexual responses of males before
having sex. It is also helpful to have sex in a comfortable, relaxed, private setting, free of guilt, stress, and
fear.
Resources
PERIODICALS

‘‘Lengthen Your Fuse.’’ Men’s Health November1999: 56.
Rowland, David L., and Arthur L. Burnett.
‘‘Pharmacotherapy inthe Treatment of Male Sexual
Dysfunction.’’ The Journal of Sex Research
August2000: 226+.
ORGANIZATIONS

American Association for Marriage and Family Therapy.
1133 15th St. NW, Suite 300, Washington, DC 200052710. (202) 452-0109. <http://www.aamft.org.>.
American Association of Sex Educators, Counselors, and
Therapists. P.O. Box 5488, Richmond, VA 23220.
<http://www.aasect.org.>.
Sexuality Information and Education Council of the U.S.
130 W. 42nd St., Ste. 350, New York, NY 10036. (212)
819-9770. <http://www.siecus.org.>.

Ken R. Wells

Premature labor
Definition
Premature labor is the term to describe contractions of the uterus that begin at weeks 20–36 of a
pregnancy.

Description
The usual length of a human pregnancy is 38–42
weeks after the first day of the last menstrual period.
Labor is a natural series of events that indicate that
the birth process is starting. Premature labor is
defined as contractions that occur after 20 weeks
and before 37 weeks during the term of pregnancy.
The baby is more likely to survive and be healthy if
it remains in the uterus for the full term of the
3011

Premature labor

partner to be devoted to his sensations. In order to
regain equality, he should in turn spend separate time
stimulating and pleasing his mate, without
intercourse.

Premature labor

pregnancy. It is estimated that around 10% of
births in the United States occur during the premature period. Premature birth is the greatest cause
of newborn illness and death. In the United
States, prematurity has a greater impact on AfricanAmericans.

Causes and symptoms
The causes of premature labor cannot always be
determined. Some research suggests that infection of
the urinary or reproductive tract may stimulate premature labor and premature births. Multiple pregnancies (twins, triplets, etc.) are more likely to result
in to premature labor. Smoking, alcohol use, drug
abuse, and poor nutrition can increase the risk of
premature labor and birth. Adolescent mothers are
also at higher risk for premature delivery. Women
whose mothers took diethylstilbestrol (DES) when
they carried them are more likely to deliver prematurely, as are women who have had previous surgery
on the cervix.
The symptoms of premature labor can include
contractions of the uterus or tightening of the abdomen, which occurs every ten minutes or more frequently. These contractions usually increase in
frequency, duration, and intensity, and may or may
not be painful. Other symptoms associated with premature labor can include menstrual-like cramps,
abdominal cramping with or without diarrhea,
pressure or pain in the pelvic region, low backache,
or a change in the color or amount of vaginal
discharge. As labor progresses, the cervix or opening
of the uterus will open (dilate) and the tissue around
it will become thinner (efface). Premature rupture
of membranes (when the water breaks) may also
occur.
An occasional contraction can occur anytime during the pregnancy and does not necessarily indicate
that labor is starting. Premature contractions are
sometimes confused with Braxton Hicks contractions,
which can occur throughout the pregnancy. Braxton
Hicks contractions do not cause the cervix to open or
efface, and are considered ‘‘false labor.’’

Diagnosis
The health care provider will conduct a physical
examination and ask about the timing and intensity of
the contractions. A vaginal examination is the only
way to determine if the cervix has started to dilate or
efface. Urine and blood samples may be collected to
screen for infection. A vaginal culture (a cotton-tipped
3012

KEY TERMS
Braxton Hicks contractions—Tightening of the
uterus or abdomen that can occur throughout pregnancy. These contractions do not cause changes to
the cervix and are sometimes called false labor or
practice contractions.
Cervix —The opening at the bottom of the uterus,
which dilates or opens in order for the fetus to pass
into the vagina or birth canal during the delivery
process.
Contraction—A tightening of the uterus during
pregnancy. Contractions may or may not be painful
and may or may not indicate labor.

swab is used to collect some fluid and cells from the
vagina) may be done to look for a vaginal infection. A
fetal heart monitor may be placed on the mother’s
abdomen to record the heartbeat of the fetus and to
time the contractions. A fetal ultrasound may be
performed to determine the age and weight of the
fetus, the condition of the placenta, and to see if
there is more than one fetus present. Amniocentesis
will sometimes be performed. This is a procedure
where a needle-like tube is inserted through the
mother’s abdomen to draw out some of the fluid surrounding the fetus. Analysis of the amniotic fluid can
determine if the baby’s lungs are mature. A baby with
mature lungs is much more likely to survive outside the
uterus.

Treatment
The goal of treatment is to stop the premature
labor and prevent the fetus from being delivered
before it is full term. A first recommendation may be
for the woman with premature contractions to lie
down with feet elevated and to drink juice or other
fluids. If contractions continue or increase, medical
attention should be sought. In addition to bed rest,
medical care may include intravenous fluids.
Sometimes, this extra fluid is enough to stop contractions. In some cases, oral or injectable drugs like
terbutaline sulfate, ritodrine, magnesium sulfate, or
nifedipine must be given to stop the contractions.
These are generally very effective; however, as with
any drug therapy, there are risks of side effects. Some
women may need to continue on medication for the
duration of the pregnancy. Antibiotics may be prescribed if a vaginal or urinary tract infection is
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
If premature labor is managed successfully, the
pregnancy may continue normally for the delivery
of a healthy infant. Once symptoms of preterm
labor occur during the pregnancy, the mother and
fetus need to be monitored regularly since it is likely
that premature labor will occur again. If the preterm labor cannot be stopped or controlled, the
infant will be delivered prematurely. These infants
that are born prematurely have an increased risk of
health problems including birth defects, lung problems, mental retardation, blindness, deafness, and
developmental disabilities. If the infant is born too
early, its body systems may not be mature enough
for it to survive. Evaluating the infant’s lung maturity is one of the keys to determining its chance of
survival. Fetuses delivered further into pregnancy
and those with more mature lungs are more likely
to survive.

Prevention
Smoking, poor nutrition, and drug or alcohol
abuse can increase the risk of premature labor and
early delivery. Smoking and drug or alcohol use
should be stopped. A healthy diet and prenatal
vitamin supplements (prescribed by the health care
provider) are important for the growth of the fetus
and the health of the mother. Pregnant women are
advised to see a health care provider early in the
pregnancy and receive regular prenatal examinations
throughout the pregnancy. The health care provider
should be informed of any medications that the
mother is receiving and any health conditions that
exist before and during the pregnancy.
Resources
ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914) 4287100. resourcecenter@modimes.org. <http://
www.modimes.org>.
OTHER

‘‘Am I in Labor?’’ The Virtual Hospital Page. University of
Iowa. <http://www.vh.org>.

Altha Roberts Edgren
GALE ENCYCLOPEDIA OF MEDICINE

Premature menopause
Definition
The average age at which American women go
through menopause is 51 years. If menopause (hormonal changes at the end of the female reproductive
years) occurs before age 40, it is said to be premature
menopause. Possible causes include autoimmune problems and common cancer treatments.

Description
About half of all women will go through menopause before age 51 and the rest will go through it
after. Most women will finish menopause between
the ages of 42 and 58. A small number of women will
find that their periods stop prematurely, before age 40.

Causes and symptoms
There are many possible causes of premature
menopause. Women who have premature menopause
often have autoimmune disorders like thyroid disease
or diabetes mellitus. In these diseases, the body produces antibodies to one or more of its own organs.
These antibodies interfere with the normal function of
the organ. Just as antibodies might attack the thyroid
or the pancreas (causing thyroid disease or diabetes),
antibodies may attack the ovaries and stop the production of female hormones.
Cancer treatments like chemotherapy or radiation
can cause premature menopause. The risk depends on
the type and length of treatment and the age of the
woman when she first begins radiation or
chemotherapy.
If the ovaries are surgically removed (during a
hysterectomy, for example) menopause will occur
within a few days, no matter how old the woman is.
The symptoms of premature menopause are
similar to those of menopause at any time. Menstrual
periods stop and women may notice hot flashes,
vaginal dryness, mood swings, and sleep problems.
Sometimes the first symptom of premature menopause is infertility. A woman may find that she cannot
become pregnant because she is not ovulating (producing eggs) anymore.
When menopause occurs after the ovaries are surgically removed, the symptoms begin within several
days after surgery and tend to be more severe. This
happens because the drop in the level of estrogen is
dramatic, unlike the gradual drop that usually occurs.
3013

Premature menopause

detected. If the membranes have already ruptured, it
may be difficult or impossible to stop premature labor.
If infection of the membranes that cover the fetus
(chorioamnionitis) develops, the baby must be
delivered.

Premature rupture of membranes

KEY TERMS
Autoimmune diseases—Diseases in which the body
creates antibodies that attack one of its own organs.
Follicle stimulating hormone (FSH)—A female hormone that regulates ovulation and menstruation.
Hormone
replacement
therapy
(HRT)—
Replacement of estrogen and progesterone lost by
women who have gone through menopause.
Hormone replacement therapy has been shown to
lower the risk of osteoporosis and heart disease in
elderly women.
Luteinizing hormone (LH)—A female hormone
that regulates ovulation and menstruation.
Menopause—The end of a woman’s reproductive
years. The hormonal changes that accompany
menopause include the hot flashes, vaginal dryness, mood swings, sleep problems, and the end
of menstrual periods. Commonly known as ‘‘the
change’’ or ‘‘the change of life.’’

Diagnosis
Premature menopause can be confirmed by blood
tests to measure the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels
of these hormones will be higher if menopause has
occurred.
Because premature menopause is often associated
with other hormonal problems, women who have premature menopause should be screened for diabetes,
thyroid disease, and similar diseases.

Treatment
There is no treatment to reverse premature menopause. Hormone replacement therapy (HRT) can prevent the common symptoms of menopause and lower
the long-term risk of osteoporosis. Women who have
premature menopause should take HRT. Estrogen
relieves the unpleasant symptoms of menopause,
including the hot flashes and the vaginal dryness.
Estrogen is especially important for women who go
through premature menopause. The long-term health
risks of menopause (osteoporosis and increased risk of
heart disease) are even more likely to occur after premature menopause. However, women who have certain medical conditions (like liver disease, uterine
cancer, or breast cancer) may not be candidates for
estrogen.
3014

If a woman still has her uterus after premature
menopause, she will also need to take progesterone
along with the estrogen. If her uterus has been
removed, estrogen alone will be enough.
Women who wish to become pregnant after premature menopause now have the option of fertility
treatments using donor eggs. This is similar to in vitro
fertilization, but the eggs come from a donor instead of
the woman who is trying to become pregnant.

Prevention
Premature menopause cannot be prevented.
Resources
BOOKS

Hall, Janet E. ‘‘Amenorrhea.’’ In Primary Care of Women,
edited by Karen J. Carlson and Stephanie A. Eisenstat.
St. Louis: Mosby-Year Book, Inc., 1995.

Amy B. Tuteur, MD

Premature rupture of
membranes
Definition
Premature rupture of membranes (PROM) is an
event that occurs during pregnancy when the sac containing the developing baby (fetus) and the amniotic
fluid bursts or develops a hole prior to the start of labor.

Description
During pregnancy, the unborn baby (fetus) is surrounded and cushioned by a liquid called amniotic
fluid. This fluid, along with the fetus and the placenta,
is enclosed within a sac called the amniotic membrane.
The amniotic fluid is important for several reasons. It
cushions and protects the fetus, allowing the fetus to
move freely. The amniotic fluid also allows the umbilical cord to float, preventing it from being compressed
and cutting off the fetus’s supply of oxygen and nutrients. The amniotic membrane contains the amniotic
fluid and protects the fetal environment from the outside world. This barrier protects the fetus from organisms (like bacteria or viruses) that could travel up the
vagina and potentially cause infection.
Although the fetus is almost always mature at
between 36–40 weeks and can be born without complication, a normal pregnancy lasts an average of 40
GALE ENCYCLOPEDIA OF MEDICINE

Sometimes the membranes burst before the start
of labor, and this is called premature rupture of membranes (PROM). There are two types of PROM. One
occurs at a point in pregnancy before normal labor
and delivery should take place. This is called preterm
PROM. The other type of PROM occurs at 36–40
weeks of pregnancy.
PROM occurs in about 10% of all pregnancies.
Only about 20% of these cases are preterm PROM.
Preterm PROM is responsible for about 34% of all
premature births.

Causes and symptoms

Labor almost always follows PROM, although
the delay between PROM and the onset of labor varies. When PROM occurs at term, labor almost always
begins within 24 hours. Earlier in pregnancy, labor can
be delayed up to a week or more after PROM. The
chance of infection increases as the time between
PROM and labor increases. While this may cause
doctors to encourage labor in the patient who has
reached term, the risk of complications in a premature
infant may cause doctors to try delaying labor and
delivery in the case of preterm PROM.
The types of infections that can complicate
PROM include amnionitis and endometritis.
Amnionitis is an infection of the amniotic membrane.
Endometritis is an infection of the innermost lining of
the uterus. Amnionitis occurs in 0.5–1% of all pregnancies. In the case of PROM at term, amnionitis
complicates about 3–15% of pregnancies. About 15–
23% of all cases of preterm PROM will be complicated
by amnionitis. The presence of amnionitis puts the
fetus at great risk of developing an overwhelming
infection (sepsis) circulating throughout its bloodstream. Preterm babies are the most susceptible to
this life-threatening infection. One type of bacteria
responsible for overwhelming infections in newborn
babies is called group B streptococci.

Diagnosis

The causes of PROM have not been clearly identified. Some risk factors include smoking, multiple
pregnancies (twins, triplets, etc.), and excess amniotic
fluid (polyhydramnios). Certain procedures carry an
increased risk of PROM, including amniocentesis (a
diagnostic test involving extraction and examination
of amniotic fluid) and cervical cerclage (a procedure
in which the uterus is sewn shut to avoid premature
labor). A condition called placental abruption is also
associated with PROM, although it is not known
which condition occurs first. In some cases of preterm
PROM, it is believed that bacterial infection of the
amniotic membrane causes it to weaken and then
break. However, most cases of PROM and infection
occur in the opposite order, with PROM occurring
first followed by an infection.

Depending on the amount of amniotic fluid leaking from the vagina, diagnosing PROM may be easy.
Some doctors note that amniotic fluid has a very
characteristic musty smell. A pelvic exam using a sterile medical instrument (speculum) may reveal a trickle
of amniotic fluid leaving the cervix, or a pool of
amniotic fluid collected behind the cervix. One of
two easy tests can be performed to confirm that the
liquid is amniotic fluid. A drop of the fluid can be
placed on nitrazine paper. Nitrazine paper is made so
that it turns from yellowish green to dark blue when it
comes in contact with amniotic fluid. Another test
involves smearing a little of the fluid on a slide, allowing it to dry, and then viewing it under a microscope.
When viewed under the microscope, dried amniotic
fluid will be easy to identify because it will look ‘‘feathery’’ like a fern.

The main symptom of PROM is fluid leaking
from the vagina. It may be a sudden, large gush of
fluid, or it may be a slow, constant trickle of fluid.
The complications that may follow PROM include
premature labor and delivery of the fetus, infections
of the mother and/or the fetus, and compression of the
umbilical cord (leading to oxygen deprivation in the
fetus).

Once PROM has been diagnosed, efforts are
made to accurately determine the age of the fetus and
the maturity of its lungs. Premature babies are at great
risk if they have immature lungs. These evaluations
can be made using amniocentesis and ultrasound
measurements of the fetus’ size. Amniocentesis also
allows the practitioner to check for infection. Other
indications of infection include a fever in the mother,

GALE ENCYCLOPEDIA OF MEDICINE

3015

Premature rupture of membranes

weeks. At the end of 40 weeks, the pregnancy is
referred to as being ‘‘term.’’ At term, labor usually
begins. During labor, the muscles of the uterus contract repeatedly. This allows the cervix to begin to
grow thinner (called effacement) and more open
(dilatation). Eventually, the cervix will become completely effaced and dilated. In the most common
sequence of events (about 90% of all deliveries), the
amniotic membrane breaks (ruptures) around this
time. The baby then leaves the uterus and enters the
birth canal. Ultimately, the baby will be delivered out
of the mother’s vagina. In the 30 minutes after the
birth of the baby, the placenta should separate from
the wall of the uterus and be delivered out of the
vagina.

Prematurity

increased heart rate of the mother and/or the fetus,
high white blood cell count in the mother, foul smelling or pus-filled discharge from the vagina, and a
tender uterus.

Treatment
Treatment of PROM depends on the stage of the
patient’s pregnancy. In PROM occurring at term, the
mother and baby will be watched closely for the first
24 hours to see if labor will begin naturally. If no labor
begins after 24 hours, most doctors will use medications to start labor. This is called inducing labor.
Labor is induced to avoid a prolonged gap between
PROM and delivery because of the increased risk of
infection.
Preterm PROM presents more difficult treatment
decisions. The younger the fetus, the more likely it may
die or suffer serious permanent damage if delivered
prematurely. Yet the risk of infection to the mother
and/or the fetus increases as the length of time from
PROM to delivery increases. Depending on the age of
the fetus and signs of infection, the doctor must decide
either to try to prevent labor and delivery until the
fetus is more mature, or to induce labor and prepare to
treat the complications of prematurity. However, the
baby will need to be delivered to avoid serious risks to
both it and the mother if infection is present, regardless of the risks of prematurity.
A variety of medications may be used in PROM:




Medication to induce labor (oxytocin) may be used,
either in the case of PROM occurring at term or in
the case of preterm PROM and infection.
Tocolytics may be given to halt or prevent the start of
labor. These may be used in the case of preterm
PROM, when there are no signs of infection.
Delaying the start of labor may give the fetus time
to develop more mature lungs.



Steroids may be used to help the fetus’ lungs mature
early. Steroids may be given in preterm PROM if the
fetus must be delivered early because of infection or
labor that cannot be stopped.



Antibiotics can be given to fight infections. Research
is being done to determine whether antibiotics
should be given prior to any symptoms of infection
to avoid the development of infection.

Prognosis
The prognosis in PROM varies. It depends in
large part on the maturity of the fetus and the development of infection.
3016

KEY TERMS
Amniocentesis—A medical procedure during
which a long, thin needle is inserted through the
abdominal and uterine walls, and into the amniotic
sac. A sample of amniotic fluid is withdrawn
through the needle for examination.
Amniotic fluid—The fluid within the amniotic sac;
the fluid surrounds, cushions, and protects the
fetus.
Amniotic membrane—The thin tissue that creates
the walls of the amniotic sac.
Cervical cerclage—A procedure in which the cervix is sewn closed; used in cases when the cervix
starts to dilate too early in a pregnancy to allow the
birth of a healthy baby.
Placenta—The organ that provides oxygen and
nutrition from the mother to the fetus during pregnancy. The placenta is attached to the wall of the
uterus, and leads to the fetus via the umbilical cord.

Prevention
The only controllable factor associated with
PROM is smoking. Cigarette smoking should always
be discontinued during a pregnancy.
Resources
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th Street, S.W., P.O. Box 96920

Rosalyn Carson-DeWitt, MD

Premature ventricular contractions see
Ventricular ectopic beats

Prematurity
Definition
The length of a normal pregnancy or gestation is
considered to be 40 weeks (280 days) from the date
of conception. Infants born before 37 weeks gestation
are considered premature and may be at risk for
complications.
GALE ENCYCLOPEDIA OF MEDICINE

More than one out of every ten infants born in the
United States is born prematurely. Advances in medical technology have made it possible for infants born
as young as 23 weeks gestational age (17 weeks premature) to survive. These premature infants, however,
are at higher risk for death or serious complications,
which include heart defects, respiratory problems,
blindness, and brain damage.

Causes and symptoms
The birth of a premature baby can be brought on
by several different factors, including premature
labor; placental abruption, in which the placenta
detaches from the uterus; placenta previa, in which
the placenta grows too low in the uterus; premature
rupture of membranes, in which the amniotic sac is
torn, causing the amniotic fluid to leak out; incompetent cervix, in which the opening to the uterus opens
too soon; and maternal toxemia, or blood poisoning.
While one of these conditions are often the immediate
reason for a premature birth, its underlying cause is
usually unknown. Prematurity is much more common
in multiple pregnancy and for mothers who have a
history of miscarriages or who have given birth to a
premature infant in the past. One of the few, and most
important, identifiable causes of prematurity is drug
abuse, particularly cocaine, by the mother.
Infants born prematurely may experience major
complications due to their low birth weight and the
immaturity of their body systems. Some of the common problems among premature infants are jaundice
(yellow discoloration of the skin and whites of the
eyes), apnea (a long pause in breathing), and inability
to breast or bottle feed. Body temperature, blood
pressure, and heart rate may be difficult to regulate
in premature infants. The lungs, digestive system, and
nervous system (including the brain) are underdeveloped in premature babies, and are particularly
vulnerable to complications. Some of the more common risks and complications of prematurity are
described below.
Respiratory distress syndrome (RDS) is the most
common problem seen in premature infants. Babies
born too soon have immature lungs that have not
developed surfactant, a protective film that helps air
sacs in the lungs to stay open. With RDS, breathing is
rapid and the center of the chest and rib cage pull
inward with each breath. Extra oxygen can be supplied
to the infant through tubes that fit into the nostrils of
the nose, or by placing the baby under an oxygen
hood. In more serious cases, the baby may have to
GALE ENCYCLOPEDIA OF MEDICINE

have a breathing tube inserted and receive air from a
respirator or ventilator. A surfactant drug can be
given in some cases to coat the lung tissue. Extra
oxygen may be need for a few days or weeks, depending on how small and premature the baby was at birth.
Bronchopulmonary dysplasia is the development of
scar tissue in the lungs, and can occur in severe cases
of RDS.
Necrotizing enterocolitis (NEC) is a further complication of prematurity. In this condition, part of the
baby’s intestines are destroyed as a result of bacterial
infection. In cases where only the innermost lining of
the bowel dies, the infant’s body can regenerate it over
time; however, if the full thickness of a portion dies, it
must be removed surgically and an opening (ostemy)
must be made for the passage of wastes until the infant
is healthy enough for the remaining ends to be sewn
together. Because NEC is potentially fatal, doctors are
quick to respond to its symptoms, which include
lethargy, vomiting, a swollen and/or red abdomen,
fever, and blood in the stool. Measures include taking
the infant off mouth feedings and feeding him or her
intravenously; administering antibiotics; and removing air and fluids from the digestive tract via a nasal
tube. Approximately 70% of NEC cases can be
successfully treated without surgery.
Intraventricular hemorrhage (IVH) is another serious complication of prematurity. It is a condition in
which immature and fragile blood vessels within the
brain burst and bleed into the hollow chambers (ventricles) normally reserved for cerebrospinal fluid and
into the tissue surrounding them. Physicians grade the
severity of IVH according to a scale of I–IV, with I
being bleeding confined to a small area around the
burst vessels and IV being an extensive collection of
blood not only in the ventricles, but in the brain tissue
itself. Grades I and II are not uncommon, and the
baby’s body usually reabsorbs the blood with no ill
effects. However, more severe IVH can result in hydrocephalus, a potentially fatal condition in which too
much fluid collects in the ventricles, exerting increased
pressure on the brain and causing the baby’s head to
expand abnormally. To drain fluid and relieve pressure on the brain, doctors will either perform lumbar
punctures, a procedure in which a needle is inserted
into the spinal canal to drain fluids; install a reservoir,
a tube that drains fluid from a ventricle and into an
artificial chamber under or on top of the scalp; or
install a ventricular shunt, a tube that drains fluid
from the ventricles and into the abdomen, where it is
reabsorbed by the body. Infants who are at high risk
for IVH usually have an ultrasound taken of their
brain in the first week after birth, followed by others
3017

Prematurity

Description

Prematurity

if bleeding is detected. IVH cannot be prevented; however, close monitoring can ensure that procedures to
reduce fluid in the brain are implemented quickly to
minimize possible damage.
Apnea of prematurity is a condition in which the
infant stops breathing for periods lasting up to 20
seconds. It is often associated with a slowing of the
heart rate. The baby may become pale, or the skin
color may change to a blue or purplish hue. Apnea
occurs most commonly when the infant is asleep.
Infants with serious apnea may need medications to
stimulate breathing or oxygen through a tube inserted
in the nose. Some infants may be placed on a ventilator
or respirator with a breathing tube inserted into the
airway. As the baby gets older, and the lungs and brain
tissues mature, the breathing usually becomes more
regular. A group of researchers in Cleveland reported
in 2003, however, that children who were born prematurely are 3–5 times more likely to develop sleepdisordered breathing by age 10 than children who
were full-term babies.
As the fetus develops, it receives the oxygen it
needs from the mother’s blood system. Most of the
blood in the infant’s system bypasses the lungs. Once
the baby is born, its own blood must start pumping
through the lungs to get oxygen. Normally, this bypass
duct closes within the first few hours or days after
birth. If it does not close, the baby may have trouble
getting enough oxygen on its own. Patent ductus arteriosus is a condition in which the duct that channels
blood between two main arteries does not close after
the baby is born. In some cases, a drug, indomethacin,
can be given to close the duct. Surgery may be required
if the duct does not close on its own as the baby
develops.
Retinopathy of prematurity is a condition in
which the blood vessels in the baby’s eyes do not
develop normally, and can, in some cases, result in
blindness. Premature infants are also more susceptible
to infections. They are born with fewer antibodies,
which are necessary to fight off infections.

Diagnosis
Many of the problems associated with prematurity depend on how early the baby is born and how
much it weighs at birth. The most accurate way of
determining the gestational age of an infant in utero
is calculating from a known date of conception or
using ultrasound imaging to observe development.
When a baby is born, doctors can use the Dubowitz
exam to estimate gestational age. This standardized
test scores responses to 33 specific neurological stimuli
3018

to estimate the infant’s neural development. Once the
baby’s gestational age and weight are determined,
further tests and electronic fetal monitoring may need
to be used to diagnose problems or to track the baby’s
condition. A blood pressure monitor may be wrapped
around the arm or leg. Several types of monitors can
be taped to the skin. A heart monitor or cardiorespiratory monitor may be attached to the baby’s chest,
abdomen, arms, or legs with adhesive patches to monitor breathing and heart rate. A thermometer probe
may be taped on the skin to monitor body temperature. Blood samples may be taken from a vein or
artery. X rays or ultrasound imaging may be used to
examine the heart, lungs, and other internal organs.

Treatment
Treatment depends on the types of complications
that are present. It is not unusual for a premature
infant to be placed in a heat-controlled unit (an incubator) to maintain its body temperature. Infants that
are having trouble breathing on their own may need
oxygen either pumped into the incubator, administered through small tubes placed in their nostrils, or
through a respirator or ventilator, which pumps air
into a breathing tube inserted into the airway. The
infant may require fluids and nutrients to be administered through an intravenous line in which a small
needle is inserted into a vein in the hand, foot, arm,
leg, or scalp. If the baby needs drugs or medications,
they may also be administered through the intravenous line. Another type of line may be inserted into the
baby’s umbilical cord. This can be used to draw blood
samples or to administer medications or nutrients. If
heart rate is irregular, the baby may have heart monitor leads taped to the chest. Many premature infants
require time and support with breathing and feeding
until they mature enough to breathe and eat unassisted. Depending on the complications, the baby
may require drugs or surgery.
A form of treatment that is being recommended by
many mainstream practitioners as of 2003 is massage
therapy. Research has shown that the risks of massaging preterm infants are minimal, and that the infants
benefit from improved developmental scores, more
rapid weight gain, and earlier discharge from the hospital. An additional benefit of massage therapy is closer
bonding between the parents and their newborn child.

Prognosis
Advances in medical care have made it possible
for many premature infants to survive and develop
normally. However, whether or not a premature infant
GALE ENCYCLOPEDIA OF MEDICINE



21 weeks or less: 0% survival rate



22 weeks: 0–10% survival rate



23 weeks: 10–35% survival rate



24 weeks: 40–70% survival rate



25 weeks: 50–80% survival rate



26 weeks: 80–90% survival rate



27 weeks: greater than 90% survival rate

Physicians cannot predict long-term complications
of prematurity; some consequences may not become
evident until the child is school-aged. Minor disabilities
like learning problems, poor coordination, or short
attention span may be the result of premature birth,
but can be overcome with early intervention. The risks
of serious long-term complications depend on many
factors, including how premature the infant was at
birth, weight at birth, and the presence or absence of
breathing problems. Gender is a definite factor: a
Swedish study published in 2003 found that boys are
at greater risk of death or serious long-term consequences of prematurity than girls; for example, 60%
of boys born at 24 weeeks’ gestation die, compared to
38% mortality for girls. The development of infection
or the presence of a birth defect can also affect longterm prognosis. Infections in premature and very low
birth weight infants are a risk factor for later disorders
of the nervous system; a study done at Johns Hopkins
reported that 77 out of a group of 213 premature
infants developed neurologic disorders. Severe disabilities like brain damage, blindness, and chronic lung
problems are possible and may require ongoing care.

Prevention
Some of the risks and complications of premature
delivery can be reduced if the mother receives good
prenatal care, follows a healthy diet, avoids alcohol or
drug consumption, and refrains from cigarette smoking. In some cases of premature labor, the mother may
be placed on bed rest or given drugs that can stop
labor contractions for days or weeks, giving the developing infant more time to develop before delivery. The
physician may prescribe a steroid medication to be
given to the mother before the delivery to help speed
up the baby’s lung development. The availability of
neonatal intensive care unit, a special hospital unit
equipped and trained to deal with premature infants,
can also increase the chances of survival.
A new medication may help to prevent spontaneous
premature births. Researchers at Wake Forest
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Apnea—A long pause in breathing.
Dubowitz exam—A standardized test that scores
responses to 33 specific neurological stimuli to
estimate an infant’s neural development and,
hence, gestational age.
Intraventricular hemorrhage (IVH)—A condition
in which blood vessels within the brain burst and
bleed into the hollow chambers (ventricles) normally reserved for cerebrospinal fluid and into the
tissue surrounding them.
Jaundice—Yellow discoloration of skin and whites
of the eyes that results from excess bilirubin in the
body’s system.
Necrotizing enterocolitis (NEC)—A condition in
which part of the intestines are destroyed as a result
of bacterial infection.
Respiratory distress syndrome (RDS)—Condition
in which a premature infant with immature lungs
does not develop surfactant, a protective film that
helps air sacs in the lungs to stay open. RDS is the
most common problem seen in premature infants.
Retinopathy of prematurity—A condition in which
the blood vessels in a premature infant’s eyes do
not develop normally, and can, in some cases,
result in blindness.
Surfactant—A protective film that helps air sacs in
the lungs to stay open. Premature infants may not
have developed this protective layer before birth
and are more susceptible to respiratory problems
without it. Some surfactant drugs are available.
These can be given through a respirator and will
coat the lungs when the baby breathes the drug in.

University reported in June 2003 that a drug known
as 17 alpha-hydroxyprogesterone caproate not only
reduced the number of premature births in a group of
women who received weekly injections of the drug compared to a placebo group, but also lowered the rates of
necrotizing enterocolitis, intraventricular hemorrhage,
and need for supplemental oxygen in their infants.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Premature Infant.’’ In The Merck Manual of Diagnosis
and Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
3019

Prematurity

will survive is still intimately tied to his or her gestational age:

Premenstrual dysphoric disorder

PERIODICALS

Beachy, J. M. ‘‘Premature Infant Massage in the NICU.’’
Neonatal Network 22 (May-June 2003): 39–45.
Holcroft, C. J., K. J. Blakemore, M. Allen, and E. M.
Graham. ‘‘Association of Prematurity and Neonatal
Infection with Neurologic Morbidity in Very Low Birth
Weight Infants.’’ Obstetrics and Gynecology 101 (June
2003): 1249–1253.
Ingemarsson, I. ‘‘Gender Aspects of Preterm Birth.’’ British
Journal of Obstetrics and Gynecology 110, Supplement
20 (April 2003): 34–38.
Meis, P. J., M. Klebanoff, E. Thom, et al. ‘‘Prevention of
Recurrent Preterm Delivery by 17 AlphaHydroxyprogesterone Caproate.’’ New England Journal
of Medicine 348 (June 12, 2003): 2379–2385.
Rosen, C. L., E. K. Larkin, H. L. Kirchner, et al.
‘‘Prevalence and Risk Factors for Sleep-Disordered
Breathing in 8- to 11-Year-Old Children: Association
with Race and Prematurity.’’ Journal of Pediatrics 142
(April 2003): 383–389.
Ward, R. M., and J. C. Beachy. ‘‘Neonatal Complications
Following Preterm Birth.’’ British Journal of Obstetrics
and Gynecology 110, Supplement 20 (April 2003): 8–16.
ORGANIZATIONS

American Academy of Pediatrics (AAP). 141 Northwest
Point Boulevard, Elk Grove Village, IL 60007. (847)
434-4000. <http://www.aap.org>.
National Institute of Child Health and Human
Development (NICHD) Information Resource Center
(IRC). P. O. Box 3006, Rockville, MD 20847. (800) 3702943. <http://www.nichd.nih.gov>.
OTHER

Brazy, J. E. For Parents of Preemies. <http://
www2.medsch.wisc.edu/childrenshosp/
parents_of_preemies/index.html>.
Levison, Donna. ‘‘When Is It Too Early? A Guide to Help
Prevent Premature Birth.’’ Health Net. <http://
www.health-net.com/preme.htm>.
‘‘Survival of Extremely Premature Babies.’’ Dr. Plain Talk
Health Care Information. <http://
www.drplaintalk.org>.

Altha Roberts Edgren
Rebecca J. Frey, PhD

Premenstrual dysphoric
disorder
Definition
Premenstrual dysphoric disorder (PMDD) is a collection of physical and emotional symptoms that occurs
5 to 11 days before a woman’s period begins, and goes
3020

away once menstruation starts. The most severe form
of premenstrual syndrome (PMS) is PMDD.

Description
PMS is estimated to affect 70–90% of childbearing
age. The more severe form of the disorder, PMDD,
affects 3–5% of women of childbearing age. Up to
40% of women have PMDD symptoms that are so
severe they interfere with their daily activities. It is
more common in women in their late 20s and early 40s,
who have at least one child and a history of depression,
anxiety/tension, affective lability, or irritability/anger.

Causes and symptoms
Although the actual cause of PMDD is not
known, it is believed to be related to hormonal
changes that occur before menstruation. There are
more than 150 signs and symptoms attributed to
PMDD, and every woman experiences different ones
at different times. There seem to be socioeconomic and
genetic factors that precipitate PMDD. Twin studies
have demonstrated a positive correlation with heritability and PMDD symptoms. Anti-anxiety medications have been shown to help improve symptoms
associated with PMDD. The most common symptoms
include headache, swelling of ankles, feet, and hands,
backache, abdominal cramps, heaviness or pain,
bloating and/or gas, muscle spasms, breast tenderness,
weight gain, recurrent cold sores, acne, nausea, constipation or diarrhea, food cravings, anxiety or panic,
confusion, difficulty concentrating and forgetfulness,
poor judgment, and depression.

Diagnosis
PMDD is diagnosed when symptoms occur during the second half of the menstrual cycle (14 days or
more after the first day of a woman’s period), are
absent for about seven days after the period ends,
increase in severity as the cycle progresses, go away
when the menstrual flow begins or shortly thereafter,
and occur for at least three consecutive menstrual
cycles. There are no tests to diagnose it. The diagnosis
of PMDD emphasizes and requires psychologically
important mood symptoms.

Treatment
Recently, the Food and Drug Administration
approved the first prescription drug for the treatment
of PMDD, Serafem (fluoxetine). Additionally, nonsteroidal anti-inflammatory drugs, such as ibuprofen
GALE ENCYCLOPEDIA OF MEDICINE

National Association for Premenstrual Syndrome. 7 Swift’s
Court, High Street, Seal, Kent TN15 0EG UK +44 (0)
1732 760011<www.PMDD.org.uk>.

Antidepressant—A medication used to relieve the
symptoms of clinical depression.
Beta blockers—Class of drug, including Corgard
(nadolol), and Lanoxin (digoxin), that primarily
work by blunting the action of adrenaline, the
body’s natural fight-or-flight chemical.
Nonsteroidal anti-inflammatory drugs—This class
of drugs includes aspirin and ibuprofen, and primarily works by interfering with the formation of
prostaglandins, enzymes implicated in pain and
inflammation.

and aspirin, may help with bloating and pain; betablockers may help with migraines; anti-anxiety medications, such as buspirone or alpraxolam, may help
with anxiety; and certain other antidepressants in
addition to Serafem may help with depression.

Premenstrual syndrome
Definition
Premenstrual syndrome (PMS) refers to symptoms that occur between ovulation and the onset of
menstruation. The symptoms include both physical
symptoms, such as breast tenderness, back pain,
abdominal cramps, headache, and changes in appetite,
as well as psychological symptoms of anxiety, depression, and unrest. Severe forms of this syndrome are
referred to as premenstrual dysphoric disorder
(PMDD). These symptoms may be related to hormones and emotional disorders.

Alternative treatment
Non-pharmaceutical treatments include a variety
of lifestyle changes, such as following a healthy diet,
exercise, stress relief therapies, and even such alternative therapies as aromatherapy. Certain vitamins and
supplements may also help, such as vitamin B6, calcium, magnesium, and vitamin E. Certain herbs may
also help with symptom relief, including vitex, black
cohosh, valerian, kava kava, and St. John’s wort.

Prognosis
The prognosis varies for each woman, and is largely dependent on how much work she is willing to do
in terms of lifestyle changes. Additionally, planning
for PMDD symptoms, joining a support group, and
communicating with her spouse and family can help
minimize the negative effects of PMDD and its impact
on a woman’s home and work environments.

Prevention
Some women may find their PMDD disappears
periodically. Diet and nutritional supplements can have
the greatest impact in preventing PMDD.
Resources
ORGANIZATIONS

Advancement of Women’s Health Research. 1828 L Street,
N.W., Suite 625 Washington, DC 20036. 202-223-8224.
<http://www.womens-health.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Approximately 75% of all menstruating women
experience some symptoms that occur before or during menstruation. PMS encompasses symptoms severe
enough to interfere with daily life. About 3–seven% of
women experience the more severe PMDD. These
symptoms can last 4–10 days and can have a substantial impact on a woman’s life.
The reason some women get severe PMS while
others have none is not understood. PMS symptoms
usually begin at about age 20–30 years. The disease
may run in families and is also more prone to occur in
women with a history of psychological problems.
Overall however, it is difficult to predict who is most
at risk for PMS.

Causes and symptoms
Because PMS is restricted to the second half of a
woman’s menstrual cycle, after ovulation, it is thought
that hormones play a role. During a woman’s monthly
menstrual cycle, which lasts 24–35 days, hormone
levels change. The hormone estrogen gradually rises
during the first half of a woman’s cycle, the preovulatory phase, and falls dramatically at ovulation. After
ovulation, the postovulatory phase, progesterone
levels gradually increase until menstruation occurs.
Both estrogen and progesterone are secreted by the
ovaries, which are responsible for producing the eggs.
3021

Premenstrual syndrome

KEY TERMS

Premenstrual syndrome

The main role of these hormones is to cause thickening
of the lining of the uterus (endometrium). However,
estrogen and progesterone also affect other parts of
the body, including the brain. In the brain and nervous
system, estrogen can affect the levels of neurotransmitters, such as serotonin. Serotonin has long been
known to have an effect on emotions, as well as eating
behavior. It is thought that when estrogen levels go
down during the postovulatory phase of the menstrual
cycle, decreases in serotonin levels follow. Whether
these changes in estrogen, progesterone, and serotonin
are responsible for the emotional aspects of PMS is
not known with certainty. However, most researchers
agree that the chemical transmission of signals in the
brain and nervous system is in some way related to
PMS. This is supported by the fact that the times
following childbirth and menopause are also associated
with both depression and low estrogen levels.
Symptoms for PMS are varied and many, including both physical and emotional aspects that range
from mild to severe. The physical symptoms include:
bloating, headaches, food cravings, abdominal
cramps, headaches, tension, and breast tenderness.
Emotional aspects include mood swings, irritability,
and depression.

(only in extreme cases) surgery to remove the ovaries.
Hormone treatment usually involves oral contraceptives. This treatment, as well as removal of the ovaries,
is used to prevent ovulation and the changes in hormones that accompany ovulation. Recent studies,
however, indicate that hormone treatment has little
effect over placebo.
Antidepressants
The most progress in the treatment of PMS and
PMDD has been through the use of antidepressant
drugs. The most effective of these include sertraline
(Zoloft), fluoxetine (Prozac), and paroxetine (Paxil).
They are termed selective serotonin reuptake inhibitors
(SSRIs) and act by indirectly increasing the brain
serotonin levels, thus stabilizing emotions. Some doctors prescribe antidepressant treatment for PMS
throughout the cycle, while others direct patients to
take the drug only during the latter half of the cycle.
Antidepressants should be avoided by women wanting
to become pregnant. A recent clinical study found that
women who took sertraline had a significant improvement in productivity, social activities, and relationships compared with a placebo group. Side effects of
sertraline were found to include nausea, diarrhea, and
decreased libido.

Diagnosis
The best way to diagnose PMS is to review a
detailed diary of a woman’s symptoms for several
months. PMS is diagnosed by the presence of physical,
psychological, and behavioral symptoms that are cyclic and occur in association with the premenstrual
period of time. PMDD, which is far less common,
was officially recognized as a disease in 1987. Its diagnosis depends on the presence of at least five symptoms related to mood that disappear within a few days
of menstruation. These symptoms must interfere with
normal functions and activities of the individual. The
diagnosis of PMDD has caused controversy in fear
that it may be used against women, labeling them as
being impaired by their menstrual cycles.

Treatment
There are many treatments for PMS and PMDD
depending on the symptoms and their severity. For
mild cases, treatment includes vitamins, diuretics, and
pain relievers. Vitamins E and B6 may decrease breast
tenderness and help with fatigue and mood swings in
some women. Diuretics that remove excess fluid from
the body seem to work for some women. For more
severe cases and for PMDD, treatments available
include antidepressant drugs, hormone treatment, or
3022

Alternative treatment
There are alternative treatments that can both
affect serotonin and hormone responses, as well as
affect some of the physical symptoms of PMS.
Vitamins and minerals
Some women find relief with the use of vitamin
and mineral supplements. Magnesium can reduce the
fluid retention that causes bloating, while calcium may
decrease both irritability and bloating. Magnesium
and calcium also help relax smooth muscles and this
may reduce cramping. Vitamin E may reduce breast
tenderness, nervous tension, fatigue, and insomnia.
Vitamin B6 may decrease fluid retention, fatigue, irritability, and mood swings. Vitamin B5 supports the
adrenal glands and may help reduce fatigue.
Phytoestrogens and Natural Progesterone
The Mexican wild yam (Dioscorea villosa) contains a substance that may be converted to progesterone in the body. Because this substance is readily
absorbed through the skin, it can be found as an
ingredient in many skin creams. (Some products also
have natural progesterone added to them.) Some
GALE ENCYCLOPEDIA OF MEDICINE

progesterone in the body, also may relieve the anxiety
and depression associated with PMS.

Antidepressant—A drug used to control depression.
Estrogen—A female hormone important in the
menstrual cycle.
Neurotransmitter—A chemical messenger used to
transmit an impulse from one nerve to the next.
Phytoestrogens—Compounds found in plants that
can mimic the effects of estrogen in the body.
Progesterone—A female hormone important in the
menstrual cycle.
Serotonin—A neurotransmitter important in regulating mood.

herbalists believe that these products can have a progesterone-like effect on the body and decrease some of
the symptoms of PMS.
The most important way to alter hormone levels
may be by eating more phytoestrogens. These plantderived compounds have an effect similar to estrogen
in the body. One of the richest sources of phytoestrogens is soy products, such as tofu. Additionally, many
supplements can be found that contain black cohosh
(Cimicifugaracemosa) or dong quai (Angelica sinensis),
which are herbs high in phytoestrogens. Red clover
(Trifolium pratense), alfalfa (Medicago sativa), licorice
(Glycyrrhiza glabra), hops (Humulus lupulus), and
legumes are also high in phytoestrogens. Increasing
the consumption of phytoestrogens is also associated
with decreased risks of osteoporosis, cancer, and heart
disease.
Antidepressant Alternatives
Many antidepressants act by increasing serotonin
levels. An alternative means of achieving this is to eat
more carbohydrates. For instance, two cups of cereal
or a cup of pasta have enough carbohydrates to effectively increase serotonin levels. An herb known as
St. John’s wort (Hypericum perforatum) has stood up
to scientific trials as an effective antidepressant. As
with the standard antidepressants, however, it must
be taken continuously and does not show an effect until
used for 46 weeks. There are also herbs, such as skullcap (Scutellaria lateriflora) and kava (Piper methysticum), that can relieve the anxiety and irritability that
often accompany depression. An advantage of these
herbs is that they can be taken when symptoms occur
rather than continually. Chaste tree (Vitex agnuscastus) in addition to helping rebalance estrogen and
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The prognosis for women with both PMS and
PMDD is good. Most women who are treated for
these disorders do well.

Prevention
Maintaining a good diet, one low in sugars and
fats and high in phytoestrogens and complex carbohydrates, may prevent some of the symptoms of PMS.
Women should try to exercise three times a week, keep
in generally good health, and maintain a positive self
image. Because PMS is often associated with stress,
avoidance of stress or developing better means to deal
with stress can be important.
Resources
PERIODICALS

Yonkers, Kimberly A., et al. ‘‘Symptomatic Improvement of
Premenstrual Dysphoric Disorder with Sertraline
Treatment: A Randomized Controlled Trial.’’ Journal
of the American Medical Association 278 (September 24,
1997): 983-989.

Cindy L. A. Jones, PhD

Prenatal surgery
Definition
Prenatal surgery is a surgical procedure performed on a fetus prior to birth.

Purpose
In most cases prenatal surgery is performed only
when the fetus is not expected to survive delivery or
live long after birth without prenatal intervention. The
most common prenatal surgeries are for conditions
in which the newborn will not be able to breathe on
its own.
Most prenatal surgeries are performed for:


urinary tract obstructions in males, usually caused by
a narrowing of the urinary tract, in which urine backs
up and injures the kidneys. About 10% of fetal urinary tract obstructions require prenatal surgery to
3023

Prenatal surgery

KEY TERMS

Prenatal surgery

prevent multiple abnormalities and depleted amniotic fluid.










congenital diaphragmatic hernia (CDH), a condition
in which the diaphragm—the muscle that separates
the chest and the abdomen—does form completely.
Without surgery about 50% of fetuses with CDH do
not survive after birth because of underdeveloped
lungs.
congenital cystic adenomatoid malformation
(CCAM), a condition in which one or more lobes
of the lungs become fluid-filled sacs called cysts.
Large CCAMs may prevent lung development,
cause heart failure, or prevent the fetus from ingesting amniotic fluid.
sacrococcygeal teratoma (SCT), tumors at the base
of the tailbone. The most common tumor in newborns, occurring in one out of every 35,000–40,000
births, some prenatal SCTs are very large, hard, and
full of blood vessels, and can stress the heart.
twin-twin transfusion syndrome (TTTS), a condition
in which, because of abnormal blood-vessel connections in the placenta, one twin pumps the circulating
blood for both twins. Affecting up to 15% of twins
sharing a placenta (monochorionic), TTTS can lead
to a variety of problems including heart failure.
twin:twin reverse arterial perfusion (TRAP)
sequence, a condition in which one twin lacks a
heart. Occurring in about 1% of monochorionic
twins, the healthy twin pumps all of the blood and,
if untreated, 50–75% of these normal twins die.

Other conditions that may be treated by prenatal
surgery include:


various congenital defects that block air passages
and will prevent the newborn from breathing on its
own



various lung malformations



omphalocele, a birth defect in which portions of the
stomach, liver, and intestines protrude through an
opening in the abdominal wall





fetal gastroschisis—a birth defect in which the stomach and intestines protrude through improperly
formed abdominal wall muscles and float in the
amniotic fluid



bowel obstructions, usually caused by a narrowing in
the small intestine



hypoplastic left heart syndrome, in which the blood
flow through the left side of the heart is obstructed



X-linked
syndrome

3024

severe

combined

immunodeficiency

spina bifida (myelomeningocele)—the second most
common birth defect in the United States, affecting
one out of every 2,000 newborns. It is a lesion or
hole where the nerves of the spinal cord are not
completely enclosed and is not considered to be lifethreatening.

Precautions
Prenatal surgery involves:


serious risks for the mother and fetus



travel to a hospital that performs the procedure



possibly having to stay near the hospital until
delivery



extended postoperative bed rest, sometimes until
delivery



a significant financial commitment.

Description
Prenatal surgery may be referred to as fetal surgery,
antenatal surgery, or maternal-fetal surgery. There are
only about 600 candidates for prenatal surgery in the
United States each year. Of these, only about 10%
actually undergo the procedure. Most prenatal surgeries are performed between 18 and 26 weeks of gestation. Some surgeries may not be covered by insurance.
Prenatal surgery usually requires a general anesthetic, although sometimes an epidural anesthetic to
numb the abdominal region may be used. The fetus
receives the anesthetic via the mother’s blood. An
anesthesiologist and a perinatologist monitor the
heart rates of the mother and fetus during the
procedure.
Prenatal surgeries include:


inserting a device into the fetal bladder to drain urine
into the amniotic sac for treating urinary tract
obstruction



draining or removing CCAMs



destroying blood vessels leading to a large SCT



amnioreduction for TTTS, in which a syringe
through the mother’s abdomen is used to remove
fluid from the overfilled amniotic sac and replace it
in the depleted sac of the twin pumping the blood.
The procedure that may be repeated during the
course of the pregnancy.



destroying abnormal blood vessel connections in the
placenta of TTTS twins



severing the connections between TRAP sequence
twins
GALE ENCYCLOPEDIA OF MEDICINE

experimental hematopoietic-stem-cell transplants
for X-linked severe combined immunodeficiency
syndrome



closing the lesion in spina bifida
Open surgeries

In open prenatal surgeries incisions are made
through the mother’s abdominal wall and the fetus is
partially removed from the uterus or the entire uterus
is removed through the mother’s abdomen. Using
ultrasound as a guide, the surgeon feels for the affected
fetal part. The surgeon may knead and push on the
uterus to move or flip the fetus away from the placenta, the disk-shaped organ within the uterus that
supplies the fetal blood. A narrow tube is placed
through a tiny hole in the uterine wall to drain and
collect the amniotic fluid. Opening the uterus is the
riskiest part of prenatal surgery. The first incision is
made at a point away from the placenta to prevent
damaging it. Following the procedure the fetus is
replaced in the uterus and the incision is stitched.
Prior to the final stitch the amniotic fluid is re-injected
into the uterus. The uterus is repositioned in the
mother’s body cavity and her abdominal wall is closed.
The first successful open fetal surgery was performed in 1981 for a urinary tract obstruction. The
first successful open fetal surgery for CDH was performed in 1989.
Prenatal open surgery for CCAM requires opening the fetus’s chest. If a large cyst does not have a
hard component, procedures called thoracoamniotic
shunting or catheter decompression may be used to
drain it. Otherwise the surgeon must remove part or
all of the cyst. The first successful resection (removal)
of a CCAM from a fetal lung was performed in 1990.
The first resectioning of a fetal SCT was performed
in 1992.
In prenatal surgery for spina bifida, An incision
the size of a small fist is made in the uterus. The
surgeon loosens and lifts the tissues of the spinalcanal lesion and stitches them closed. Between 1997
and 2004, more than 200 open surgeries were performed for spina bifida. As of 2005 the surgery was
available only as part of a prospective randomized
clinical trial.
Less invasive procedures
For urinary tract obstructions a needle may be
used to insert a catheter through the mother’s abdomen and uterus and into the fetal bladder where it
drains the urine into the amniotic fluid. The catheter
GALE ENCYCLOPEDIA OF MEDICINE

may have a wire mesh that expands in the bladder to
prevent it from plugging up or dislodging.
The first successful fetoscopic temporary tracheal
occlusion for CDH was performed in 1996. Small
openings are made in the uterus and a tiny fiberoptic fetoscope is inserted to guide the operation. A
needle-like instrument is used to place a balloon in the
fetus’s trachea to prevent lung fluid from escaping
through the mouth, enabling the lungs to expand,
grow, and push the abdominal organs out of the
chest. The balloon is removed at birth.
Hypoplastic left heart syndrome is treated by passing a needle, guided by ultrasound, through the
mother’s abdominal wall, into the uterus, and the
fetal heart. A catheter is passed through the needle
across the fetus’s aortic valve. A balloon is inflated,
opening the valve and allowing blood to flow through
the left side of the heart.
RADIOFREQUENCY ABLATION. Radiofrequency ablation (RFA) sometimes is used for SCT. Guided by
ultrasound a needle is inserted through the mother’s
abdomen and uterus and into the tumor. Radiofrequency waves sent through the needle destroy the
blood supply to the tumor with heat. This slows the
tumor’s growth and may enable the fetus to survive
until delivery. The first RFA of a SCT was performed
in 1998.

TRAP sequence also may be treated by RFA. A
3-mm needle targets the exact point where the blood
enters the twin without a heart. Using an echocardiographic device, RFA is applied until the blood vessels
and surrounding tissue are destroyed and the blood
flow is halted. This procedure has eliminated the need
for open surgery to treat TRAP sequence.
LASER TREATMENT. If TTTS does not respond to
amnioreduction, laser treatment to halt the abnormal
blood circulation may be attempted. A thin fetoscope is
inserted through the mother’s abdominal and uterine
walls and into the amniotic cavity of the recipient twin
to examine the surface placental blood vessels. The
abnormal blood vessel connections are located and
eliminated with a laser beam. The first successful fetoscopic laser treatment for TTTS was performed in 1999.
EXIT. Ex utero intrapartum treatment (EXIT) is a
surgery performed for a congenital defect that blocks a
fetal airway. The fetus is removed from the womb by
cesarean section but the umbilical cord is left intact so
that the mother’s placenta continues to sustain the
fetus. After the air passage is cleared, the umbilical
cord is cut and the newborn can breathe on its own.
The EXIT procedure is used for various types of airway obstruction including CCAM.

3025

Prenatal surgery



Prenatal surgery

Preparation
The decision to perform prenatal surgery is made
on the basis of detailed ultrasound imaging of the
fetus—including echocardiograms that use ultrasound
to obtain images of the heart—as well as other diagnostic tools. Consultations include a perinatologist, a
neonatologist, a pediatric surgeon, a clinical nurse
specialist, and a social worker. Since additional congenital defects preclude prenatal surgery, amniocentesis or chorionic villi sampling (CVS) are used to check
for chromosomal abnormalities in the fetus.
Prior to surgery the mother must:


arrange for postoperative bed rest to prevent preterm
labor



prepare for the possibility of remaining near the
hospital until delivery



receive betamethasone, a steroid, in two intramuscular injections 12–24 hours apart to accelerate fetal
lung maturation



wear a fetal/uterine monitor

The mother usually receives medications called
tocolytics to prevent contractions and labor during
and after surgery:

contractions. She sees a perinatologist once a week
and has at least one ultrasound per week.

Risks
Most prenatal surgeries are high risk and may be
considered experimental. The greatest risk is that the
placenta will be nicked during surgery, causing blood
hemorrhaging, uterine contractions, and birth of a
premature infant who may not survive. Preterm
labor is the most common complication of prenatal
surgery. Fetoscopic surgeries are less dangerous and
traumatic than open fetal surgery and reduce the risk
of premature labor. Subsequent children of a mother
who has undergone prenatal surgery usually are delivered by cesarean section because of uterine scarring.
Maternal risks
Risks to the mother include:


extensive blood loss



complications from general anesthesia



side effects—potentially fatal—from medications to
control premature labor



rupture of the uterine incision



terbutalin



infection of the wound or uterus



indocin suppositories before surgery and up to
48 hours after surgery



psychological stress



inability to have additional children



death.



magnesium sulfate for one to two days after surgery
with careful monitoring



nifedipine every four to six hours as the indocin is
decreased, continuing until 37 weeks of gestation or
delivery

Aftercare
In addition to usual post-surgical care, the
mother:


usually remains in the hospital for four to seven days



lies on her side to help prevent contractions and
ensure the best possible fetal circulation



has a transparent dressing over the abdominal incision for fetal monitoring



has continuous electronic fetal/uterine monitoring to
check the fetal heart, the uterine response to tocolytics, and to watch for signs of preterm labor.

After discharge from the hospital the mother is on
modified bed rest, lying on her side, until 37 weeks of
gestation. This increases blood flow to the fetus and
reduces pressure on the cervix to help prevent uterine
3026

Fetal risks
All fetuses that undergo surgery are born prematurely. Those born even six weeks early are at risk for
walking and talking delays and learning disabilities.
Infants born at 30 weeks of gestation or less are at risk
for blindness, cerebral palsy, and brain hemorrhages.
About 25% of women undergoing prenatal surgery lose some amniotic fluid, often because of leakage
at the uterine incision. Amniotic fluid is essential for
lung development and protects the fetus from injury
and infection. If all of the amniotic fluid is lost, the
fetal lungs may not develop properly. Without the
fluid cushion in which the fetus floats, the umbilical
cord may be compressed, causing death.
Other risks to the fetus include:


birth during surgery



separation of the tissues surrounding the amniotic
fluid sac and the uterus, causing early delivery or
interference with blood flow to some fetal body
part such as an arm or leg
GALE ENCYCLOPEDIA OF MEDICINE

Amniocentesis—Withdrawal of amniotic fluid
through the mother’s abdominal wall, using a needle
and syringe, to test for fetal disorders.
Amniotic fluid—The watery fluid within the amniotic sac that surrounds the fetus.
Cesarean section—C-section; incision through the
abdominal and uterine walls to deliver a baby.
Chorion—The outermost membrane of the sac
enclosing the fetus.
Chorionic villus sampling (CVS)—The removal of
fetal cells from the chorion for the diagnosis of
genetic disorders.
Congenital cystic adenomatoid malformation
(CCAM)—A condition in which one or more lobes
of the fetal lungs develop into fluid-filled sacs called
cysts.
Congenital diaphragmatic hernia (CDH)—A condition in which the fetal diaphragm—the muscle dividing the chest and abdominal cavity—does not close
completely.
Echocardiography—Ultrasonic examination of the
heart.

Monochorionic twins—Twins that share a single
placenta.
Omphalocele—A congenital hernia in which a small
portion of the fetal abdominal contents, covered by a
membrane sac, protrudes into the base of the umbilical cord.
Placenta—The organ within the uterus that provides
nourishment to the fetus.
Radiofrequency ablation (RFA)—A procedure in
which radiofrequency waves are used to destroy
blood vessels and tissues.
Sacrococcygeal teratoma (SCT)—A tumor occurring
at the base of the fetus’s tailbone.
Spina bifida—Myelomeningocele; a congenital
defect in which the fetal backbone and spinal canal
do not close completely, allowing the spinal cord
and its surrounding membranes to protrude.
Tocolytic—A medication that inhibits uterine
contractions.
Twin:twin reverse arterial perfusion (TRAP)
sequence—A condition in which one fetus lacks a
heart and the other fetus pumps the blood for both.

Ex utero intrapartum treatment (EXIT)—A cesarean
section in which the infant is removed from the
uterus but the umbilical cord is not cut until after
surgery for a congenital defect that blocks an air
passage.

Twin-twin transfusion syndrome (TTTS)—A condition in monochorionic twins in which there is a connection between the two circulatory systems so that
the donor twin pumps the blood to the recipient twin
without a return of blood to the donor.

Fetoscope—A fiber-optic instrument for viewing the
fetus inside the uterus.

Ultrasound—A procedure that uses high-frequency
sound waves to image a fetus.



intrauterine infection requiring immediate birth of
the fetus



Thoracoamniotic shunting for CCAM usually
results in infant survival.



further damage to the spinal cord and nerves during
surgery to treat spina bifida



The infant survival rate following prenatal removal
of solid CCAMs is about 50%.



brain damage





physical deformities



death.

RFA to slow the growth of a tumor usually enables
the fetus to survive delivery, after which the tumor
can be removed.



The infant survival rate following prenatal treatment
for TTTS is about 70%. Since TTTS is a progressive
disorder, early intervention may prevent later
complications.

Normal results
Although fetal surgeries heal without scarring, it
is difficult to predict their outcome because relatively
few have been performed:


Fetal surgery for CDH lessens the severity of the
condition so that the fetus usually survives delivery
and lives long enough to undergo corrective surgery.

GALE ENCYCLOPEDIA OF MEDICINE

Spina bifida arises during the first month of fetal
development. Fluid leaking from the spinal cord and
exposure of the cord to amniotic fluid causes damage
throughout gestation. Lesions higher up in the spinal
cord can cause severe deformities, paralysis, and
3027

Prenatal surgery

KEY TERMS

Prepregnancy counseling

mental retardation. Prenatal surgery may reduce the
abnormalities, although it does not cure the condition.
Babies who survive prenatal surgery appear to be 33–
50% less likely to have hydrocephalus, a condition that
requires surgically implanted tubes or shunts to
remove fluid from the ventricles (cavities) of the
brain. The surgery also appears to reverse hindbrain
herniation, in which the back of the brain slips down
into the spinal canal, causing breathing and swallowing problems and death in 15% of affected children.
Children who had prenatal surgery to treat spina
bifida appear to have better brain function than
those who did not. However prenatal surgery does
not prevent two of the most serious conditions associated with spina bifida: leg movement and bladder
and bowel control. As of 2005 the long-term prognosis
for these children was not known.
Resources
BOOKS

Bianchi, Diana W., et al. Fetology: Diagnosis and
Management of the Fetal Patient. New York: McGrawHill, 2000.
Casper, Monica J. The Making of an Unborn Patient: A
Social Anatomy of Fetal Surgery. New Brunswick, NJ:
Rutgers University Press, 1998.
PERIODICALS

Hedrick, Holly L., et al. ‘‘History of Fetal Diagnosis and
Therapy: Children’s Hospital of Philadelphia
Experience.’’ Fetal Diagnosis and Therapy 18, no. 2
(March/April 2003): 65–82.
Jones, Maggie. ‘‘A Miracle, and Yet.’’ New York Times
Magazine July 15, 2001: 38–43.
Kalb, Claudia. ‘‘Treating the Tiniest Patients.’’ Newsweek
June 9, 2003.
Paek, Bettina W., et al. ‘‘Advances in Fetal Surgery.’’ Female
Patient 25, no. 6 (June 2000): 15–18.
ORGANIZATIONS

Fetal Treatment Center, University of California at San
Francisco Children’s Hospital. 505 Parnassus Ave., San
Francisco, CA 94143. 800-RX-FETUS. <http://
www.ucsfhealth.org/childrens/medical_services/
surgical/fetal>.
Management of Myelomeningocele Study (MOMS).
Catherine Shaer, M.D., The George Washington
University Biostatistics Center, 6110 Executive Blvd.,
Suite 750, Rockville, MD 20852. 866-ASK-MOMS.
<http://www.spinabifidamoms.com>.
OTHER

Bunch, Kathy. Giving Baby a Chance, Before Birth.
WebMDHealth. 2001 [cited March 11, 2005].
<http://my.webmd.com/content/article/14/
3606_466.htm?lastselectedguid={5FE84E90BC77-4056-A91C-9531713CA348}>.
3028

Fetal Treatment. UCSF Children’s Hospital. April 2002
[cited March 11, 2005]. <http://www.ucsfhealth.org/
childrens/medical_services/surgical/fetal>.
Fetal Treatment: Patient Education. UCSF Children’s
Hospital. March 2003 [cited March 11, 2005]. <http://
www.ucsfhealth.org/childrens/medical_services/
surgical/fetal/moreinfo/patient_education.html>.
Mayo Clinic Staff. Spina Bifida: Treatment. Mayo
Foundation for Medical Education and Research.
December 8, 2003 [cited March 11, 2005].
<http://www.mayoclinic.com/
invoke.cfm?objectid=CB5F085A-6152-42FC8CFC55380EF705A2&dsection=8>.

Margaret Alic, Ph.D.

Prepregnancy counseling
Definition
Prepregnancy pregnancy counseling is advice
supplied by an obstetrician, nurse, certified nursemidwife, or childbirth educator about those steps a
mother-to-be and father-to-be can take in preparation
for pregnancy. Basically, it is a checklist for people to
see if they are living lives that are most accommodating to having a healthy pregnancy. Prepregnancy
counseling gives time for one to make changes before
pregnancy.

Purpose
The purpose and goal of prepregnancy counseling
is to help patients have full-term, healthy pregnancies
and babies. The counseling and education are important because lifestyle habits such as smoking or alcohol
usage can be hazardous to a developing fetus.

Precautions
Women who have diabetes should take special
precautions before pregnancy. This counseling,
usually provided by a team of professionals including
a registered dietitian, diabetes educators, an obstetrician, and others, helps to prevent early pregnancy loss
and congenital malformations in infants of diabetic
mothers.
Women who have a history of genetic disease can
opt to have genetic testing. Prepregnancy counseling
can include referrals to those specialists.
Women who are over 40 have higher cesarean
section rates. They are also more likely than younger
GALE ENCYCLOPEDIA OF MEDICINE

Women who are considering pregnancy should
avoid exposure to hazards such as chemicals, illicit
drugs, alcohol, and smoking. They should reduce
their caffeine intake and be careful not to let their
body temperatures rise to dangerous levels.

Description
Prepregnancy counseling involves communicating important aspects about nutrition, medication
use, and lifestyle months in advance of getting pregnant. Issues include diet, nutrition, exercise, smoking,
alcohol, drugs, emotional health, and referral to
genetic counseling if a patient knows of a history of
inherited disease.

Preparation
The mother-to-be should stop using birth control
pills to allow for at least two regular menstrual cycles
to occur before conception. This requires that she stop
taking birth control pills several months before getting
pregnant.
Other steps to prepare for pregnancy include:
Being at optimal weight. Women should not go on
prepregnancy weight loss diets unless they are under
the care of a physician because abrupt weight loss can
affect the mother’s menstrual cycle and reduce
fertility.
Eating a balanced diet. This is achieved by taking a
prenatal vitamin provided by a health care provider
and focusing on nutrients that are important for a
developing fetus. These include folate, or folic acid,
which is important for the development of the baby’s
brain and spinal cord. Folate can be found in fortified
cereals, citrus fruits, and green leafy vegetables.
Calcium is important for baby and mother. It helps
the baby’s bones to develop normally and keeps the
mother from suffering a calcium deficiency during
pregnancy. Iron keeps the mother from developing
anemia during pregnancy. Good sources of iron are
green leafy vegetables, red meat, beans, and fortified
cereal. Fiber helps mothers avoid constipation, a common occurrence during pregnancy. Good sources of
fiber include beans, fruits, and vegetables.
Exercising on a regular basis. One should exercise
for general overall health.
Undergoing routine physical and dental exams.
These include having a physical and breast
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Preeclampsia—Also called toxemia, preeclampsia
is a condition during pregnancy that results in high
blood pressure, swelling that doesn’t go away and
large amounts of protein in the urine. Without
treatment, it can progress to a dangerous condition
called eclampsia, in which a woman goes into
convulsions.

examination and Pap test. Other tests might be recommended according to a woman’s health and genetic
history. They should also report any prescription
drugs, over-the-counter medications, or natural vitamins and herbs they are taking. This is the time for a
woman to make sure she is up to date on her immunizations. A dental exam, with x rays, can eliminate the
need to have x rays while pregnant.
Getting psychological support. Mental support is
also important in the prepregnancy stage. This can
help a woman to relax and better prepare mentally
and physically for what lies ahead.

Risks
About 10–15% of couples in the United States
experience infertility. When couples should seek medical evaluation and an infertility work-up depends on
their ages. Generally, it takes longer for older couples
to conceive. Prepregnancy counseling might include a
referral to such a specialist. While infertility is often
treatable, treatment can be expensive, emotionally
difficult, and time-consuming. About 10 percent of
the time, doctors cannot detect a reason for the
infertility.
There always is the risk that a pregnancy goes
awry or a baby is born with a medical condition,
regardless of whether or not a person has had prepregnancy counseling.

Normal results
The counseling can provide guidelines for people
so that they can maximize their chances to have emotionally and physically healthy pregnancies and
healthy babies.

Abnormal results
Many abnormal results, such as genetic conditions, miscarriage, preeclampsia (also known as
3029

Prepregnancy counseling

women to have conditions such as high blood pressure, and are more likely to have babies with genetic
problems, such as Down syndrome.

Presbyopia

toxemia), and preterm births, cannot be avoided even
with prepregnancy counseling. Still, some abnormal
results, such as miscarriages and preterm births, may
occur when mothers and fathers lead unhealthy lifestyles despite their counseling.
Resources
ORGANIZATIONS

‘‘About infertility and pregnancy.’’ Ciberdiet.com. <http://
www.cyberdiet.com/modules/ip/reproductive_years/
preparation/nutritional_health.html>.
‘‘General pre pregnancy guidelines.’’
<http://parentsplace.com>.
‘‘Preconception care of women with diabetes.’’ American
Diabetes Association. <http://journal.diabetes.org/
FullText/Supplements/DiabetesCare/
Supplement100/S65.htm>.
‘‘Take a health inventory before pregnancy.’’ UC Davis
Health System. UC Davis Medical Center. 2315
Stockton Blvd. Sacramento, CA 95817. (916) 734-2011.
<http:www.ucdmc.ucdavis.edu>.
Trish Booth, M.A., LCCE, FACCE, Childbirth Educator,
Educational Process Consultant. 7507 Northfield Lane.
Manlius, N.Y. 13104. (315) 682-2922.

Lisette Hilton

Presbyopia
Definition
The term presbyopia means ‘‘old eye’’ and is a
vision condition involving the loss of the eye’s ability
to focus on close objects.

Description
Presbyopia is a condition that occurs as a part of
normal aging and is not considered to be an eye disease. The process occurs gradually over a number of
years. Symptoms are usually noticeable by age 40–45
and continue to develop until the process stabilizes
some 10–20 years later. Presbyopia occurs without
regard to other eye conditions.

Causes and symptoms
In the eye, the crystalline lens is located just behind
the iris and the pupil. Tiny ciliary muscles pull and push
the lens, adjusting its curvature, and thereby adjusting
the eye’s focal power to bring objects into focus. As
individuals age, the lens becomes less flexible and elastic,
and the muscles become less powerful. Because these
3030

changes result in inadequate adjustment of the lens of
the eye for various distances, objects that are close will
appear blurry. The major cause of presbyopia is loss of
elasticity of the lens of the eye. Loss of ciliary muscle
power, however, is also believed to contribute to the
problem.
Symptoms of presbyopia result in the inability to
focus on objects close at hand. As the lens hardens, it is
unable to focus the rays of light that come from nearby
objects. Individuals typically have difficulty reading
small print, such as that in telephone directories and
newspaper advertisements, and may need to hold
reading materials at arm’s length. Symptoms include
headache and eyestrain when doing close work, blurry
vision, and eye fatigue. Symptoms may be worse early
in the morning or when individuals are fatigued. Dim
lighting may also aggravate the problem.

Diagnosis
Presbyopia is officially diagnosed during an eye
examination conducted by eye specialists, such as
optometrists or ophthalmologists. After completing
optometric college, doctors of optometry screen
patients for eye problems and prescribe glasses and
contact lenses. In contrast, ophthalmologists are medical doctors who specialize in eye diseases. They perform eye surgery, treat eye diseases, and also prescribe
glasses and contact lenses.
A comprehensive eye examination requires at least
30 minutes. Part of the examination will assess vision
while reading by using various strength lenses. If the
pupils are dilated with drugs to permit a thorough
examination of the retina, an additional hour is
required. The cost of eye examinations can range
from $40 to $250 depending on the complexity and
site of the examination and the qualifications and
reputation of the examiner. Some insurers cover the
cost of routine eye examinations, while others do not.
A thorough eye examination is recommended at regular intervals during the adult and aging years to
monitor and diagnose eye conditions. However, individuals frequently self-diagnose presbyopia by trying
on inexpensive mass-produced reading glasses until
they find a pair that permits reading without strain.

Treatment
Presbyopia cannot be cured, but individuals can
compensate for it by wearing reading, bifocal, or trifocal eyeglasses. A convex lens is used to make up for the
lost automatic focusing power of the eye. Half-glasses
can be worn, which leave the top open and uncorrected
for distance vision. Bifocals achieve the same goal by
GALE ENCYCLOPEDIA OF MEDICINE

In addition to glasses, contact lenses have also
been found to be useful in the treatment of presbyopia.
The two common types of contact lenses prescribed
for this condition are bifocal and monovision contact
lenses. Bifocal contact lenses are similar to bifocal
glasses. The top portion of the lens serves as the distance lens while the lower serves as the near vision lens.
To prevent rotation while in the eye, bifocal contacts
use a specially manufactured type of lens. Good candidates for bifocal lenses are those patients who have a
good tear film (moist eyes), good binocular vision
(ability to focus both eyes together) and visual acuity
in each eye, and no disease or abnormalities in the
eyelids. The bifocal contact lens wearer must be motivated to invest the time it requires to maintain contact
lenses and be involved in occupations that do not
impose high visual demands. Further, bifocal contact
lenses may limit binocular vision. Bifocal contact
lenses are relatively expensive, in part due to the time
it takes the patient to be accurately fitted.
An alternative to wearing eyeglasses or bifocal
contact lenses is monovision contact lenses.
Monovision fitting provides one contact lens that corrects for near vision and a second contact lens for the
alternate eye that corrects for distance vision. If distance vision is normal, the individual wears only a
single contact lens for near vision. Monovision works
by having one eye focus for distant objects while the
other eye becomes the reading eye. The brain learns to
adapt to this and will automatically use the correct eye
depending on the location of material in view.
Advantages of monovision are patient acceptability,
convenience, and lower cost.
Several problems exist with the use of contact
lenses in the treatment of presbyopia. Some individuals
experience headache and fatigue during the adjustment
period or find the slight decrease in visual acuity unacceptable. Monovision contact lenses usually result in a
small reduction in high-contrast visual acuity when
compared with bifocal contact lenses.

Prognosis
The changes in vision due to aging usually start in a
person’s early 40s and continue for several decades. At
some point, there is no further development of presbyopia, as the ability to accommodate is virtually gone.

Prevention
There is no known way to prevent presbyopia.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Accommodation—The ability of the eye to change
its focus from near to distant objects.
Binocular vision—Using both eyes at the same
time to see an image.
Ciliary muscles—The small muscles that permit the
lens to change its shape in order to focus on near or
distant objects.
Lens (or crystalline lens)—The eye structure
behind the iris and pupil that helps focus light on
the retina.
Visual acuity—Sharpness or clearness of vision.

Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100.
<http://www.aoanet.org>.
Lighthouse National Center for Vision and Aging. 111 E.
59th St., New York, NY 10022. (800) 334-5497.
<http://www.lighthouse.org>.
National Eye Institute. 2020 Vision Place, Bethesda, MD
20892-3655. (301) 496-5248.
<http://www.nei.nih.gov>.

Elaine Souder, PhD

Presenile dementia see Alzheimer’s disease
Pressure sores see Bedsores
Preterm labor see Premature labor

Priapism
Definition
Priapism is a rare condition that causes a persistent, and often painful, penile erection.

Description
Priapism is drug induced, injury related, or caused
by disease, not sexual desire. As in a normal erection,
the penis fills with blood and becomes erect. However,
unlike a normal erection that dissipates after sexual
3031

Priapism

allowing correction of other refractive errors (improper
focusing of images on the retina of the eye).

Prickly heat

KEY TERMS
Antineoplastic—A drug used to inhibit the growth
and spread of cancerous cells.
Doppler ultrasound—An imaging technique using
ultrasound that can detect moving liquids.
Infarction—Death of tissue due to inadequate
blood supply.
Nuclear scanning—Use of injected radioactive
elements to analyze blood flow.
Sickle cell anemia—A hereditary abnormality of
blood cells in which some are deformed and may
plug up small blood vessels.

activity ends, the persistent erection caused by priapism is maintained because the blood in the penile shaft
does not drain. The shaft remains hard, while the tip of
the penis is soft. If it is not relieved promptly, priapism
can lead to permanent scarring of the penis and inability to have a normal erection.

Causes and symptoms
Priapism is caused by leukemia, sickle cell disease,
or spinal cord injury. It has also been associated as a
rare side effect to trazodone (Desyrel), a drug prescribed to treat depression. An overdose of selfinjected chemicals to counteract impotence has also
been responsible for priapism. The chemicals are
directly injected into the penis, and at least a quarter
of all men who have used this method of treatment for
over three months develop priapism.

method. That failing, there are more extensive surgical
procedures available. One of them shuts off much of
the blood supply to the penis so that it can relax. If the
problem is due to a sickle cell crisis, treatment of the
crisis with oxygen or transfusion may suffice.

Prognosis
If priapism is relieved within the first 12–24 hours,
there is usually no residual damage. After that, permanent impotence may result, since the high pressure in
the penis compromises blood flow and leads to tissue
death (infarction).

Prevention
An antineoplastic drug (hydroxyurea) may prevent future episodes of priapism for patients with
sickle cell disease.
Resources
BOOKS

Wertheimer, Neil. Total Health for Men. Emmaus, PA:
Rodale Press, 1995.
PERIODICALS

Werthman, P., and J. Rajfer. ‘‘MUSE Therapy: Preliminary
Clinical Observations.’’ Urology 50 (November 1997):
809-811.

J. Ricker Polsdorfer, MD

Prickly heat
Definition

Diagnosis
A physical examination is needed to diagnose
priapism. Further testing, including nuclear scanning
or Doppler ultrasound, will diagnose the underlying
cause of the condition.

Also known as sweat retention syndrome or miliaria rubra, prickly heat is a common disorder of the
sweat glands.

Description
Treatment
There are three methods of treatment. The most
effective is the injection of medicines into the penis
that allow the blood to escape. Cold packs may also
be applied to alleviate the condition, but this method
becomes ineffective after about eight hours. For the
most serious cases and those that do not respond to the
first two treatments, a needle can be used to remove
the blood. The tissues may need to be flushed with
saline or diluted medications by the same needle
3032

The skin contains two types of glands: one produces oil and the other produces sweat. Sweat glands
are coil-shaped and extend deep into the skin. They are
capable of plugging up at several different depths,
producing four distinct skin rashes.


Miliaria crystallina is the most superficial of the
occlusions. At this level, only the thin upper layer
of skin is affected. Little blisters of sweat that cannot
escape to the surface form. A bad sunburn as it just
starts to blister can look exactly like this.
GALE ENCYCLOPEDIA OF MEDICINE





Deeper plugging causes miliaria rubra as the sweat
seeps into the living layers of skin, where it irritates
and itches.
Miliaria pustulosais (a complication of miliaria
rubra) occurs when the sweat is infected with pyogenic bacteria and turns to pus.
Deeper still is miliaria profunda. The skin is dry, and
goose bumps may or may not appear.

There are two requirements for each of these
phases of sweat retention: hot enough weather to
induce sweating, and failure of the sweat to reach the
surface.

Causes and symptoms
Best evidence as of 2001, suggests that bacteria
form the plugs in the sweat glands. These bacteria are
probably normal inhabitants of the skin, and why
they suddenly interfere with sweat flow is still not
known.
Infants are more likely to get miliaria rubra than
adults. All the sweat retention rashes are also more
likely to occur in hot, humid weather.
Besides itching, these conditions prevent sweat
from cooling the body, which it is supposed to do
by evaporating from the skin surface. Sweating is the
most important cooling mechanism available in hot
environments. If it does not work effectively, the
body can rapidly become too hot, with severe and
even lethal consequences. Before entering this
phase of heat stroke, there will be a period of heat
exhaustion symptoms–dizziness, thirst, weakness–
when the body is still effectively maintaining its
temperature. Then the temperature rises, often
rapidly, to 104–58F (408C) and beyond. This is an
emergency of the first order, necessitating immediate
and rapid cooling. The best method is immersion in
ice water.

Diagnosis
Rash and dry skin in hot weather are usually
sufficient to diagnose these conditions.

Treatment
The rash itself may be treated with topical antipruritics (itch relievers). Preparations containing aloe,
menthol, camphor, eucalyptus oil, and similar ingredients are available commercially. Even more effective, particularly for widespread itching in hot
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Ambient—Surrounding.
Pyogenic—Capable
of
generating
pus.
Streptococcus, Staphococcus and bowel bacteria
are the primary pyogenic organisms.
Syndrome—A collection of abnormalities that
occur together often enough to suggest they have
a common cause.

weather, are cool baths with corn starch and/or oatmeal (about 0.5 lb [224 g] of each per bathtub-full).
Dermatologists can peel off the upper layers of
skin using a special ultraviolet light. This will remove
the plugs and restore sweating, but is not necessary in
most cases.
Much more important, however, is to realize that
the body cannot cool itself adequately without sweating. Careful monitoring for symptoms of heat disease
is important. If they appear, some decrease in the
ambient temperature must be achieved by moving to
the shade, taking a cool bath or shower, or turning up
the air conditioner.

Prognosis
The rash disappears in a day with cooler temperatures, but the skin may not recover its ability
to sweat for two weeks–the time needed to replace
the top layers of skin with new growth from
below.

Prevention
Experimental application of topical antiseptics
like hexachlorophene almost completely prevented
these rashes.
Resources
BOOKS

Berger, Timothy G. ‘‘Skin and Appendages.’’ In
CurrentMedical Diagnosis and Treatment, 1996, edited
by Stephen McPhee, et al., 35 the ed.
Stamford:Appleton & Lange, 1995.

J. Ricker Polsdorfer, MD

Primaquine see Antimalarial drugs
3033

Prickly heat



Primary biliary cirrhosis

Primary biliary cirrhosis
Definition
Primary biliary cirrhosis is the gradual destruction
of the biliary system for unknown reasons.

Description
Although the cause of this serious condition is not
known, it has many features to suggest that it is an
autoimmune disease. Autoimmunity describes the
process whereby the body’s defense mechanisms are
turned against itself. The immune system is supposed
to recognize and attack only dangerous foreign invaders like germs, but many times it attacks, for no
apparent reason, the cells of the body itself.
Autoimmune reactions occur in many different tissues
of the body, creating a great variety of diseases.
Primary biliary cirrhosis progressively destroys
the system that drains bile from the liver into the
intestines. Bile is a collection of waste products
excreted by the liver. As the disease progresses it also
scars the liver, leading to cirrhosis. In some patients,
the disease destroys the liver in as little as five years. In
others, it may lie dormant for a decade or more.

A close-up image indicating biliary cirrhosis of the liver.
(Custom Medical Stock Photo. Reproduced by permission.)

KEY TERMS
Biopsy—Surgical
removal
of
tissue
for
examination.
Cirrhosis—Scarring, usually referring to the liver.
Immunosuppression—Techniques to prevent
transplant graft rejection by the body’s immune
system.

Causes and symptoms
Ninety percent of patients with this disease are
women between the ages of 35 and 60. The first sign of
it may be an abnormal blood test on routine examination. Itching is a common early symptom, caused by a
buildup of bile in the skin. Fatigue is also common in the
early stages of the disease. Later symptoms include jaundice from the accumulation of bile and specific nutritional deficiencies–bruising from vitamin K deficiency,
bone pain from vitamin D deficiency, night blindness
from vitamin A deficiency, and skin rashes, possibly
from vitamin E or essential fatty acid deficiency. All
these vitamin problems are related to the absence of bile
to assist in the absorption of nutrients from the intestines.

has had consistently positive results. Ursodeoxycholic
acid, a chemical that dissolves gall stones, provides
substantial symptomatic relief. It is still unclear if it
slows liver damage.
Primary biliary cirrhosis is a major reason for liver
transplantation. Patients do so well that this is becoming the treatment of choice. As experience, technique,
and immunosuppression progressively improve,
patients with this disease will come to transplant surgery earlier and earlier in their disease course.

Prognosis
Diagnosis
Blood tests strongly suggest the correct diagnosis,
but a liver biopsy is needed for confirmation. It is also
usually necessary to x ray the biliary system to look for
other causes of obstruction.

Treatment
Of the many medicines tried to relieve the symptoms and slow the progress of this disease, only one
3034

So far, this disease has not returned in a transplanted liver.
Resources
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.

J. Ricker Polsdorfer, MD
GALE ENCYCLOPEDIA OF MEDICINE

Primary polycythemia see Polycythemia
vera
Primary pulmonary hypertension see
Pulmonary hypertension
PRK see Photorefractive keratectomy and
laser-assisted inPro time see Prothrombin time
Probenecid see Gout drugs
Procainamide see Antiarrhythmic drugs
Prochlorperazine see Antinausea drugs

Proctitis
Definition
Proctitis is an inflammation of the rectum.

Diagnosis
Proctitis is diagnosed by a patient history and
physical examination. It is confirmed by a proctoscopy (examination of the rectum with an endoscope
inserted through the anus). Proctoscopy usually shows
a red, sore, inflamed lining of the rectum. Biopsies,
smears, and lab cultures of rectal material are used to
determine the exact cause of the inflammation so that
the underlying cause can be treated appropriately.
Since the two problems often occur together, in
the presence of proctitis, the large bowel should be
examined for ulcerative colitis.

Treatment
Once the underlying cause of the inflammation is
diagnosed, appropriate treatment begins. Antibiotics
are given for bacterial infections. There is no cure for
genital herpes, but the antiviral drug, acyclovir, is often
prescribed to reduce symptoms. Corticosteroid suppositories or ointments such as hydrocortisone are used to
lessen discomfort, and the patient is encouraged to take
warm baths to ease painful symptoms. Ulcerative proctitis often responds well to corticosteroid enemas or
foam, or to sulfasalazine and related drugs.

Description
Proctitis affects mainly adolescents and adults. It
is most common in men around age 30. Proctitis is
caused by several different sexually transmitted diseases. Male homosexuals and people who practice
anal intercourse are more likely to suffer from proctitis. Patients who have AIDS or who are immunocompromised are also more at risk.

Causes and symptoms
Proctitis is caused most often by sexually transmitted diseases, including gonorrhea, syphilis, herpes
simplex (genital herpes), candidiasis, and chlamydia. It
can also be caused by inflammatory bowel diseases,
such as Crohn’s disease, or ulcerative colitis (a chronic
recurrent ulceration in the colon)–with which it is a
very common component. Occasionally it is caused by
an amoeba that causes dysentery.
Discharge of blood and mucus and intense pain in
the area of the rectum and anus are all signs of proctitis. Patients feel the urge to have frequent bowel movements even when there is nothing present to eliminate.
They may also have constipation, diarrhea, fever, and
open sores around the anus. Other symptoms include
cramping, lower back pain, difficulty urinating, and
impotence.
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
Depending on the cause of proctitis, alternative
medicine has several types of treatments available. If
proctitis is related to gonorrhea, syphilis, or chlamydia, appropriate antibiotic treatment is recommended. Supplementation with Lactobacillus
acidophilus is also recommended during and following antibiotic therapy to help rebuild normal gut
flora that is destroyed by antibiotics. If proctitis is
herpes-related, antiviral herbs taken internally, as
well as applied topically, can be be helpful. Sitz
baths and compresses of herbal infusions (herbs
steeped in hot water) and decoctions (herbal extracts
prepared by boiling the herb in water) can be very
effective. Among the herbs recommended
are calendula (Calendula officinalis), comfrey
(Symphytum officinale), and plantain (Plantago
major). Proctitis related to candidiasis requires dietary alterations, especially elimination of sugar from
the diet. Any immunocompromised person needs
close medical attention. If proctitis is related to
inflammatory bowel diseases, the resolution of the
underlying condition should contribute to resolution
of the proctitis. Acupuncture and homeopathic treatment can be very useful in resolving inflammatory
bowel diseases.
3035

Proctitis

Primary degenerative dementia see
Alzheimer’s disease

Progressive multifocal leukoencephalopathy

KEY TERMS
Candidiasis—A common fungal infection caused by
yeast that thrives in moist, warm areas of the body.
Chlamydia—A gonorrhea-like bacterial infection.
Proctoscopy—A procedurein which a thin tube
containing a camera and a light is inserted into
the rectum so that the doctor can visually inspect it.
Rectum—The final section of the large intestine.
Ulcerative colitis—Chronic ulceration of the colon
and rectum.

Prognosis
Proctitis caused by bacteria is curable with antibiotics. Genital herpes is not curable. Although symptoms can be suppressed, proctitis may reoccur.
Patients with AIDS are especially susceptible to candidiasis infections, which may be hard to control.
Recovering from proctitis caused by inflammatory
bowel diseases is variable and depends on successful
management of those diseases. Severe proctitis can
result in permanent narrowing of the anus.

Prevention
Proctitis is best prevented by using condoms and
practicing safer sex to prevent acquiring sexually
transmitted diseases. Avoiding anal intercourse also
helps prevent damage to the rectum.
Resources
OTHER

ThriveOnline. ‘‘Proctitis.’’ <http://
thriveonline.oxygen.com>.

Tish Davidson, A.M.

Proctosigmoidoscopy see Sigmoidoscopy

caused by opportunistic infection of brain cells (oligodendrocytes and astrocytes) by the JC virus (JCV).

Description
PML is an opportunistic infection associated with
AIDS and certain cancers. It occurs in people with
inadequate immune response and carries a poor prognosis. The incidence of PML, once quite rare, is rising
as the numbers of people living with persistently compromised immune systems rises. An estimated 2–7%
of people with HIV disease will develop PML. The
infection also occurs among people undergoing longterm chemotherapy for cancer. PML is not considered
a contagious disease. According to the Centers for
Disease Control definition of AIDS, PML in the presence of HIV infection is sufficient to form a diagnosis
of AIDS.

Causes and symptoms
Although at least 80% of the adults in the United
States have been exposed to JC virus (as evidenced by
the presence of antibodies to this virus), very few will
develop PML. Little is certain about what causes JCV
to produce active disease, but the virus persists in the
kidneys of otherwise healthy people without making
them ill. Recent evidence suggests that after prolonged
compromise of the immune system, the virus changes
into a form that can reach brain tissue and cause
disease. In PML, the JCV infects and kills the cells
(oligodendrocytes) that produce myelin, which is
needed to form the sheath that surrounds and protects
nerves.
About 45% of people with PML experience vision
problems, most often a blindness affecting half of the
visual field of each eye. Mental impairment affects
about 38% of people with PML. Eventually, about
75% experience extreme weakness. Other symptoms
include lack of coordination, paralysis on one side of
the body (hemiparesis), and problems in speaking or
using language.

Progesterone assay see Sex hormones tests
Diagnosis

Progressive multifocal
leukoencephalopathy
Definition
Progressive multifocal leukoencephalopathy
(PML) is a rapidly progressive neuromuscular disease
3036

Diagnosis is difficult, but usually relies on a neurologist and radiologist assessing the white matter of
the brain on a computed tomography scan or a magnetic resonance imaging (MRI). Tests of the cerebrospinal fluid can help distinguish between PML
and other diseases, such as multiple sclerosis and
acute hemorrhagic leukoencephalopathy. The rapid
clinical progression in immunocompromised patients
is another distinguishing factor.
GALE ENCYCLOPEDIA OF MEDICINE

Multifocal—Having many focal points. In progressive multifocal leukoencephalopathy, it means that
damage caused by the disease occurs at multiple
sites.
Opportunistic infection—A illness caused by
infecting organisms that would not be able to produce disease in a person with a healthy immune
system, but are able to take advantage of an
impaired immune response.

Treatment

disease that gradually destroys nerve cells in the parts
of the brain that control eye movements, breathing,
and muscle coordination. The loss of nerve cells causes
palsy, or paralysis, that slowly gets worse as the disease progresses. The palsy affects ability to move the
eyes, relax the muscles, and control balance.

Description
Progressive supranuclear palsy is a disease of middle age. Symptoms usually begin in the 60s, rarely
before age 45 or after age 75. Men develop PSP more
often than women do. It affects three to four people
per million each year.

Causes and symptoms

Currently, there is no known cure for PML,
although it sometimes responds to treatment in
patients with AIDS who are taking anti-HIV drugs
(such as AZT, alpha-interferon, and peptide T).
Although several agents have shown some potential
in the last few years, such as the highly toxic cancer
drug cytarabine, none are safe enough or sufficiently
effective to be approved for PML.

Prognosis
PML is usually a very aggressive disease. The time
between the onset of symptoms and death can be as
little as one to six months. However, some patients
infected with HIV have improved without receiving
treatment specifically for PML.
Resources
PERIODICALS

Royal III, Walter. ‘‘Update on Progressive
MultifocalLeukoencephalopathy.’’ The Hopkins HIV
Report 9 (March 1997).

Jill S. Lasker

Progressive supranuclear ophthalmoplegia
see Progressive supranuclear palsy

Progressive supranuclear palsy
Definition
Progressive supranuclear palsy (PSP; also known
as Steele-Richardson-Olszewski syndrome) is a rare
GALE ENCYCLOPEDIA OF MEDICINE

PSP affects the brainstem, the basal ganglia, and
the cerebellum. The brainstem is located at the top of
the spinal cord. It controls the most basic functions
needed for survival–the involuntary (unwilled) movements such as breathing, blood pressure, and heart
rate. The brainstem has three parts: the medulla
oblongata, the pons, and the midbrain. The parts
affected by PSP are the pons, which controls facial
nerves and the muscles that turn the eye outward,
and the midbrain, the visual center. The basal ganglia
are islands of nerve cells located deep within the brain.
They are involved in the initiation of voluntary
(willed) movement and control of emotion. Damage
to the basal ganglia causes muscle stiffness (spasticity)
and tremors. The cerebellum is located at the base of
the skull. It controls balance and muscle coordination.
Vision is controlled by groups of cells called nuclei
in the brainstem. In PSP, the nuclei continue to function, but the mechanisms that control the nuclei are
destroyed. The term supranuclear means that the
damage is done above (supra) the nuclei. Patients
with PSP have difficulty with voluntary (willed) eye
movement. At first, the difficulty only occurs in trying
to look down. As the disease progresses, ability to
move the eyes right and left is also affected.
However, reflex or unwilled eye movements remain
normal. Thus, when the patient’s head is tilted
upwards, the eyes move to look down. These reflex
movements remain normal until late in the course of
the disease. The upper eyelids may be pulled back, the
eyebrows raised, and the brow wrinkled, causing a
typical wide-eyed stare. Rate of blinking may decrease
from the normal 20–30 per minute to three to five per
minute. It becomes difficult to walk downstairs, to
maintain eye contact during conversation, or to
move the eyes up and down to read.
3037

Progressive supranuclear palsy

KEY TERMS

Progressive supranuclear palsy

The earliest symptoms of PSP may be frequent
falls or stiff, slow movements of the arms and legs.
These symptoms may appear as much as five years
before the characteristic vision problems. Walking
becomes increasingly awkward, and some patients
tend to lean and fall backward. Facial muscles may
be weak, causing slurred speech and difficulty swallowing. Sleep may be disturbed and thought processes
slowed. Although memory remains intact, the slowed
speech and thought patterns and the rigid facial
expression may be mistaken for senile dementia or
Alzheimer’s disease. Emotional responses may become
exaggerated and inappropriate, and the patient may
experience anxiety, depression, and agitation.
The cause of PSP is not known. Most people who
develop PSP come from families with no history of the
disease, so it does not seem to be inherited, except in
certain rare instances. People who have PSP seem to
lack the neurotransmitters dopamine and homovanillic acid in the basal ganglia. Neurotransmitters are
chemicals that help carry electrical impulses along
the nervous system. Transmitting structures in brain
cells called neurofibrils become disorganized (neurofibrillary tangles). Neurofibrillary tangles are also
found in Alzheimer’s disease, but the pattern is somewhat different.

Diagnosis
PSP is sometimes mistaken for Parkinson’s disease, which is also associated with stiffness, frequent
falls, slurred speech, difficulty swallowing, and
decreased spontaneous movement. The facial expression in Parkinson’s, however, is blank or mask-like,
whereas in PSP it is a grimace and wide-eyed stare.
PSP does not cause the uncontrolled shaking (tremor)
in muscles at rest that is associated with Parkinson’s
disease. Posture is stooped in Parkinson’s disease, but
erect in PSP. Speech is of low volume in both diseases,
but is more slurred and irregular in rhythm in PSP.
Multiple strokes or abnormal accumulations of
fluid within the skull (hydrocephalus) can also cause
balance problems similar to PSP. Magnetic resonance
imaging (MRI) scans of the brain may be needed to
rule out these conditions. In advanced cases, MRI
shows characteristic abnormalities in the brainstem
described as ‘‘mouse ears.’’

KEY TERMS
Basal ganglia—Brain structure at the base of the
cerebral hemispheres, involved in controlling
movement.
Brainstem—Brain structure closest to the spinal
cord, involved in controlling vital functions, movement, sensation, and nerves supplying the head and
neck.
Cerebellum—The part of the brain involved in
coordination of movement, walking, and balance.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Parkinson’s disease—A slowly progressive disease
that destroys nerve cells. Parkinson’s is characterized by shaking in resting muscles, a stooping posture, slurred speech, muscular stiffness, and
weakness.

Parkinson’s disease, such as levodopa (Sinemet),
sometimes decrease stiffness and ease spontaneous
movement. Anticholinergic medications, such as trihexyphenidyl (Artane), which restore function to neurotransmitters, or tricyclic drugs, such as amitriptyline
(Elavil) may improve speech, walking, and inappropriate emotional responses.
Speech therapy may help manage the swallowing
and speech difficulty in PSP. As the disease progresses,
the difficulty in swallowing may cause the patient to
choke and get small amounts of food in the lungs. This
condition can cause aspiration pneumonia. The patient
may also lose too much weight. In these cases, a feeding tube may be needed. The home environment
should be modified to decrease potential injury from
falls. Walkers can be weighted in front, to prevent
backward falls and handrails can be installed in the
bathroom. Because the patient cannot look down, low
objects like throw rugs and coffee tables should be
removed. Dry eyes from infrequent blinking can be
treated with drops or ointments.

Prognosis
Treatment
PSP cannot be cured. Drugs are sometimes given
to relieve symptoms, but drug treatment is usually
disappointing. Dopaminergic medications used in
3038

The patient’s condition gradually deteriorates.
After about seven years, balance problems and stiffness make it nearly impossible for the patient to walk.
Persons with PSP become more and more immobile
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
PSP cannot be prevented.
Resources
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave., St.
Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.
Society for Progressive Supranuclear Palsy, Inc. Suite #5065
Johns Hopkins Outpatient Center, 601 N. Caroline St.,
Baltimore, MD 21287. (800) 457-4777. <http://
www.psp.org>.

Laurie Barclay, MD

Progressive systemic sclerosis see
Scleroderma

Prolactin test
Definition
Prolactin is a hormone secreted by the anterior
portion of the pituitary gland (sometimes called the
‘‘master gland’’). Its role in the male has not been
demonstrated, but in females, prolactin promotes lactation, or milk production, after childbirth.

Purpose
The prolactin test is used to diagnose pituitary
dysfunction that might be caused by a tumor called
an adenoma. In some circumstances, the test is also
used to evaluate absence of menstrual periods (amenorrhea), or spontaneous production of milk (galactorrhea) by a woman who is not pregnant or lactating.

Precautions
Stress from trauma, illness, surgery, or even nervousness about a blood test can elevate prolactin
levels. Drugs that may increase prolactin include
phenothiazines, oral contraceptives, opiates, histamine antagonists, monoamine oxidase inhibitors
GALE ENCYCLOPEDIA OF MEDICINE

(MAO inhibitors), estrogen, and antihistamines.
Drugs that can decrease values include levodopa
and dopamine.

Description
Prolactin is also known as the lactogenic hormone
or lactogen. It is essential for the development of the
mammary glands for lactation during pregnancy, and
for stimulating and maintaining lactation after childbirth. Like the human growth hormone, prolactin acts
directly on tissues, and its levels rise in response to
sleep and to physical or emotional stress. During sleep,
prolactin levels can increase to the circulating levels
found in pregnant women (as high as ten to twenty
times the normal level).
Prolactin secretion is controlled by prolactinreleasing and prolactin-inhibiting chemicals (factors)
secreted by an area of the brain called the hypothalamus. Another hormone, thyroid-releasing hormone,
or TRH, can also stimulate prolactin.
Tumors of the pituitary, called adenomas, are the
most common cause of excessive levels of prolactin.
Depending on the type of cell involved, these tumors
are also called prolactin-secreting pituitary acidophilic
or chromophobic adenomas. Moderately high prolactin levels are found to a lesser extent in women with
secondary amenorrhea, galactorrhea, low thyroid,
anorexia, and a disorder known as polycystic ovary
syndrome, a disease whose cause is not well-known.
Because high prolactin levels are more likely due
to pituitary adenoma than other causes, the prolactin
level is used to diagnose and monitor this type of
tumor. Several stimulation and suppression tests,
with TRH or levodopa, respectively, have been
designed to differentiate pituitary adenoma from
other causes of prolactin overproduction.

Preparation
This test requires a blood sample that should be
drawn in the morning at least two hours after the
patient wakes (samples drawn earlier may show
sleep-induced peak levels). The patient need not
restrict food or fluids nor limit physical activity, but
should relax for approximately 30 minutes before
the test.

Risks
Risks posed by this test are minimal, but may
include slight bleeding from the blood-drawing
site, fainting or lightheadedness after venipuncture,
3039

Prolactin test

and unable to care for themselves. Death is not caused
by the PSP itself. It is usually caused by pneumonia
related to choking on secretions or by starvation
related to swallowing difficulty. It usually occurs
within 10 years, but if good general health and nutrition are maintained, the patient may survive longer.

Prolonged QT syndrome

Prolactinoma see Galactorrhea

KEY TERMS

Prolapsed disk see Herniated disk

Adenoma—A benign tumor
Amenorrhea—The absence or abnormal stoppage
of menstrual periods.
Factor—Any of several substances necessary to
produce a result or activity in the body. The term
is used when the chemical nature of the substance
is unknown. In endocrinology, when the chemical
nature is known, factors are renamed hormones.
Galactorrhea—Excessive or spontaneous flow of
milk.
Pituitary gland—A gland located at the base of the
brain, and controlled by the hypothalamus. It controls most endocrine functions and is responsible
for things such as kidney function, lactation, and
growth and development.

or hematoma (blood
puncture site).

accumulating under the

Normal results
Reference ranges vary from laboratory to laboratory but are generally within the following values:


adult male: 0–20 ng/ml



adult female: 0–20 ng/ml



pregnant female: 20–400 ng/ml

Abnormal results
Increased prolactin levels are found in galactorrhea, amenorrhea, prolactin-secreting pituitary
tumor, infiltrative diseases of the hypothalamus, and
metastatic cancer of the pituitary gland. Higher levels
than normal are seen in stress which may be produced
by anorexia nervosa, surgery, strenuous exercise,
trauma, and in renal (kidney) failure.
Decreased prolactin levels are seen in Sheehan’s
syndrome, a condition of severe hemorrhage after
obstetric delivery that causes decreased blood supply
to the pituitary.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores
3040

Prolonged QT syndrome
Definition
Prolonged QT syndrome, also known as long QT
syndrome (LQTS), refers to a group of disorders that
increase the risk for sudden death due to an abnormal
heartbeat.

Description
Abnormal heartbeats (cardiac arrhythmias) are a
primary cause of sudden death, especially in the young
population. In the United States, an estimated 1 in
300,000 individuals per year die suddenly due to irregular heart rhythms. One of the better understood
causes of these arrhythmias is LQTS.
The QT of LQTS refers to an interval between two
points (Q and T) on the common electrocardiogram
(ECG, EKG) used to record the electrical activity of
the heart. This electrical activity, in turn, is the result
of small molecules (ions such as sodium and potassium) passing in and out of channels in the membranes
surrounding heart cells. A prolonged QT interval indicates an abnormality in electrical activity that leads to
irregularities in heart muscle contraction. One of these
irregularities is a specific pattern of very rapid contractions (tachycardia) of the lower chambers of the
heart called torsade de pointes, a type of ventricular
tachycardia. The rapid contractions, which are not
effective in pumping blood to the body, result in a
decreased flow of oxygen-rich blood to the brain.
This can result in a sudden loss of consciousness (syncope) and death.

Causes and symptoms
Both inherited and acquired forms of LQTS have
been identified. Most acquired forms are thought to be
due to certain drugs including adrenaline (epinephrine), several antihistamines and antibiotics, specific
heart medications, diuretics, and others. It has been
proposed, but not yet documented, that individuals
who experience LQTS after using one of these medications, may actually have a genetic defect that increases
their tendency to cardiac arrhythmias. Severe weight
loss such as is associated with anorexia nervosa can
GALE ENCYCLOPEDIA OF MEDICINE

Three inherited forms of LQTS have been
described to date. Jervell and Lange-Neilsen syndrome, named for the physicians who described the
condition in 1957, is associated with congenital deafness and is inherited as an autosomal recessive trait.
Romano-Ward syndrome, the most common inherited form of LQTS, was first described in the 1960’s.
It is inherited in an autosomal dominant pattern and is
not associated with other physical impairments such
as deafness. In 1995, a third type of LQTS was
reported in to occur in association with bilateral syndactyly. Little is known about the inheritance of this
form, except that reported cases have been sporadic
with no associated family history of LQTS.
As of early 2001, six different genes had been
associated with the inherited forms of LQTS, and
mutations in at least four of these genes had been
reported in a number of affected individuals and
families. The genes involved in LQTS play important
roles in the formation of ion channels in the cell membrane, and, thus, mutations in these genes disrupt
normal cardiac rhythms.
LQTS usually presents with symptoms that constitute a life-threatening emergency. Sudden loss of
consciousness or cardiac arrest can be brought on by
emotional or physical stress in young, otherwise
healthy individuals, both female and male. Fright,
anger, surprise, sudden awakening as a result of loud
sounds (alarm clock, telephone), as well as physical
activities, especially swimming, have all been reported
to precipitate an episode of cardiac arrhythmia in
susceptible individuals. Sudden death often occurs.
Although the information is preliminary, recent
research has also suggested that a small number of
SIDS (sudden infant death syndrome) cases may be
due to mutations in one or more of the genes associated with LQTS.

Diagnosis
Problems exist in diagnosing LQTS. Although the
method of diagnosis is the electrocardiogram, most
young, healthy people do not routinely undergo this
test, and, thus, their first, and possibly fatal, episode of
LQTS comes without warning. In some cases, a nonfatal episode is mistakenly treated as a seizure, and,
therefore, a follow-up assessment does not include an
electrocardiogram. In addition, some cases of LQTS
cannot be diagnosed by a routine electrocardiogram.
That is, the QT interval is not found to be prolonged in
routine testing. If LQTS is suspected either because of
GALE ENCYCLOPEDIA OF MEDICINE

a previous episode of syncope or because of a family
member with LQTS, an exercise electrocardiogram
should be performed. In all instances where an individual is diagnosed with LQTS, family members should
be thoroughly evaluated, and a detailed family history
should be taken noting any individuals with episodes
of sudden loss of consciousness and any cases of unexplained sudden death. Because many of the genes
involved in LQTS have been identified, genetic testing
can offer a more reliable means of diagnosis of other
family members at risk. The first step in determining if
this type of testing is appropriate in any particular
situation is to consult a genetic counselor or medical
geneticist.

Treatment
A conventional treatment is the oral administration of beta-blockers, medications that decrease the
input from the sympathetic nervous system to the
heart. Although beta-blockers do not correct the
abnormalities in the ion channels of the heart cells,
they do appear to decrease the occurrence of cardiac
arrhythmias. However, these medications are not
helpful in all cases, and are actually contraindicated
in some individuals. Potassium supplementation is
also being explored as a treatment in certain cases.
As the genetics of LQTS becomes better understood,
it should be possible to tailor treatments that will be
effective for each of the various gene mutations.

Alternative treatment
In some patients, severing of the sympathetic
nerve to the heart has decreased the occurrence of
arrhythmias. Pacemakers and defibrillators appear to
hold promise as new forms of treatment. As devices of
this type are developed that are smaller in size, they
may come into more widespread use, either alone or in
conjunction with specific medications.

Prognosis
LQTS is a life-long condition. Individuals who are
not diagnosed and treated are at an increased risk of
syncope and sudden death. Adequate treatment can
decrease this risk. There is no cure. Individuals with
one of the inherited forms of LQTS are at risk of
passing the mutation and the disease to their offspring.

Prevention
The risk of cardiac arrhythmias due to acquired
forms of LQTS can be decreased by avoiding the
3041

Prolonged QT syndrome

also disrupt ion balances in the heart and result in
prolongation of the QT interval.

Prophylaxis

PERIODICALS

KEY TERMS
Anorexia nervosa—A loss of appetite for food not
explainable by local disease. It is thought to have a
psychological basis.
Autosomal dominant—A pattern of inheritance in
which only one of the two copies of an autosomal
gene must be abnormal for a genetic condition or
disease to occur. An autosomal gene is a gene that
is located on one of the autosomes or non-sex
chromosomes. A person with an autosomal dominant disorder has a 50% chance of passing it to
each of their offspring.
Autosomal recessive—A pattern of inheritance in
which both copies of an autosomal gene must be
abnormal for a genetic condition or disease to
occur. An autosomal gene is a gene that is located
on one of the autosomes or non-sex chromosomes.
When both parents have one abnormal copy of the
same gene, they have a 25% chance with each
pregnancy that their offspring will have the
disorder.

Towbin, Jeffrey A., and Vatta, Matteo. ‘‘Molecular Biology
and the Prolonged QT Syndromes’’ American Journal of
Medicine 110 (April 2001): 385– 398.
Vizgirda, Vida M. ‘‘The Genetic Basis for Cardiac
Dysrhythmias and the Long QT Syndrome’’
J. Cardiovasc Nursing 13, no.4 (1999): 34–45.
ORGANIZATIONS

Sudden Arrhythimia Death Syndromes Foundation. 540
Arapeen Drive, Suite 207, Salt Lake City Utah, 84108,
(800) STOP SAD, <http://www.sads.org> or
<http://www.ihc.com/research/longqt.html>.
OTHER

American Heart Association. <http://
www.Americanheart.org/
Heart_and_Stroke_A_Z_Guide/longqt.html>.
NORD (National Organization for Rare Disorders, Inc.).
<http://www.rarediseases.org>.

Sallie Boineau Freeman, PhD

PROM see Premature rupture of membranes
Promethaz see Antihistamines

Diuretic—An agent that increases the production
of urine.
Electrocardiogram—A record of the electrical
activity of the heart showing certain waves called
P, Q, R, S, and T waves. The Q, R, S, T waves are
associated with contraction of the ventricles, the
lower two chambers of the heart.
Sympathetic nervous system—A division of the
autonomic nervous sytem, the portion of the nervous system that controls involuntary bodily functions such as heart rate.
Syndactyly—A fusion of two or more toes or
fingers.

medications and situations that trigger episodes. At
present there is no genetic therapy to correct the gene
mutations present in the inherited forms of LQTS, but
individuals who are known to have an inherited form
may also be able to lessen the risk of a life-threatening
episode by avoiding such environmental triggers and
by taking the appropriate medications.
Resources
BOOKS

Keating, Mark T., and Sanguinetti, Michael C. ‘‘Familial
Cardiac Arrhythmias.’’ In The Metabolic & Molecular
Bases of Inherited Disease, edited by C.R. Scriver, et al.
New York: McGraw-Hill Press, April 2001.
3042

Prophylaxis
Definition
A prophylaxis is a measure taken to maintain
health and prevent the spread of disease. Antibiotic
prophylaxis is the focus of this article and refers to the
use of antibiotics to prevent infections.

Purpose
Antibiotics are well known for their ability to
treat infections. But some antibiotics also are prescribed to prevent infections. This usually is done
only in certain situations or for people with particular
medical problems. For example, people with abnormal heart valves have a high risk of developing heart
valve infections after even minor surgery. This happens because bacteria from other parts of the body
get into the bloodstream during surgery and travel to
the heart valves. To prevent these infections, people
with heart valve problems often take antibiotics
before having any kind of surgery, including dental
surgery.
Antibiotics also may be prescribed to prevent
infections in people with weakened immune systems,
such as people with AIDS or people who are having
GALE ENCYCLOPEDIA OF MEDICINE

In all of these situations, a physician should be the
one to decide whether antibiotics are necessary. Unless
a physician says to do so, it is not a good idea to take
antibiotics to prevent ordinary infections.
Because the overuse of antibiotics can lead to
resistance, drugs taken to prevent infection should be
used only for a short time.

KEY TERMS
AIDS—Acquired immunodeficiency syndrome. A
disease caused by infection with the human immunodeficiency virus (HIV). In people with this disease, the immune system breaks down, opening
the door to other infections and some types of
cancer.
Antibiotic—A medicine used to treat infections.
Chemotherapy—Treatment of an illness with chemical agents. The term is usually used to describe
the treatment of cancer with drugs.
Immune system—The body’s natural defenses
against disease and infection.

Description
Among the drugs used for antibiotic prophylaxis
are amoxicillin (a type of penicillin) and fluoroquinolones such as ciprofloxacin (Cipro) and trovafloxacin
(Trovan). These drugs are available only with a physician’s prescription and come in tablet, capsule,
liquid, and injectable forms.

Recommended dosage
The recommended dosage depends on the type of
antibiotic prescribed and the reason it is being used.
For the correct dosage, check with the physician or
dentist who prescribed the medicine or the pharmacist
who filled the prescription. Be sure to take the medicine exactly as prescribed. Do not take more or less
than directed, and take the medicine only for as long as
the physician or dentist says to take it.

after taking antibiotics should get in touch with his
or her physician.

Interactions
Whether used to treat or to prevent infection,
antibiotics may interact with other medicines. When
this happens, the effects of one or both of the drugs
may change or the risk of side effects may be greater.
Anyone who takes antibiotics for any reason should
inform the physician about all the other medicines he
or she is taking and should ask whether any possible
interactions may interfere with drugs’ effects. For
details of drug interactions, see entries on specific
types of antibiotics.
Nancy Ross-Flanigan

Precautions
If the medicine causes nausea, vomiting, or diarrhea, check with the physician or dentist who prescribed it as soon as possible. Patients who are taking
antibiotics before surgery should not wait until the day
of the surgery to report problems with the medicine.
The physician or dentist needs to know right away if
problems occur.
For other specific precautions, see the entry on the
type of drug prescribed such as penicillins or
fluoroquinolones.

Side effects
Antibiotics may cause a number of side effects.
For details, see entries on specific types of antibiotics.
Anyone who has unusual or disturbing symptoms
GALE ENCYCLOPEDIA OF MEDICINE

Proportionate dwarfism see Pituitary
dwarfism
Proptosis see Exophthalmos
Prostaglandins see Drugs used in labor

Prostate biopsy
Definition
Prostate biopsy is a surgical procedure that
involves removing a small piece of prostate tissue for
microscopic examination.
3043

Prostate biopsy

chemotherapy treatments for cancer. But even healthy
people with strong immune systems may occasionally
be given preventive antibiotics–if they are having certain kinds of surgery that carry a high risk of infection,
or if they are traveling to parts of the world where they
are likely to get an infection that causes diarrhea, for
example.

Prostate biopsy

Purpose
This test is usually done to determine whether the
patient has prostate cancer. Occasionally, it may also
be used to diagnose a condition called benign prostatic
hyperplasia that causes enlargement of the prostate. In
the United States, prostate cancer is the most common
cancer among men over 50, and is the second leading
cause of cancer deaths. According to statistics released
in 2003, African American men in the United States
are at much greater risk of developing prostate cancer
after age 50 than Caucasian or Asian American men.
Prostate biopsy is recommended when a digital
rectal examination (a routine screening test for prostate diseases) reveals a lump or some other abnormality in the prostate. In addition, if blood tests reveal
that the levels of certain markers, such as PSA, are
above normal, the doctor may order a biopsy.

Description
The prostate gland is one of the three male sex
glands and lies just below the urinary bladder, in the
area behind the penis and in front of the rectum. It
secretes semen, the liquid portion of the ejaculate. The
urethra carries the urine from the urinary bladder and
the semen from the sex glands to the outside of the
body.
Prostate biopsies can be performed in three different ways. They can be performed by inserting a needle
through the perineum (the area between the base of the
penis and the rectum), by inserting a needle through
the wall of the rectum, or by cytoscopy. Before the
procedure is performed, the patient may be given a
sedative to help him relax. Patients undergoing cytoscopy may be given either general anesthesia or local
anesthesia. The doctor will ask the patient to have an
enema before carrying out the biopsy. The patient is
also given antibiotics to prevent any possible infection.
Needle biopsy via the perineum
The patient lies either on one side or on his back
with his knees up. The skin of the perineum is thoroughly cleansed with an iodine solution. A local anesthetic is injected at the site where the biopsy is
performed. Once the area is numb, the doctor makes
a small (1 in) incision in the perineum. The doctor
places one finger in the rectum to guide the placement
of the needle. The needle is then inserted into the
prostate, a small amount of tissue is collected, and
the needle is withdrawn. The needle is then re-inserted
into another part of the prostate. Tissue may be taken
from several areas. Pressure is then applied at the
3044

biopsy site to stop the bleeding. The procedure generally takes 15–30 minutes and is usually done in a
physician’s office or in a hospital operating room.
Although it sounds painful, it typically causes only
slight discomfort.
Needle biopsy via the rectum
This procedure is also done in the physician’s
office or in the hospital operating room, and is usually
done without any anesthetic, although some doctors
prefer to inject a local anesthetic, usually lidocaine.
The patient is asked to lie on his side or on his back
with his legs in stirrups. The doctor attaches a curved
needle guide to his finger and then inserts the finger
into the rectum. After firmly placing the needle guide
in the rectum, the biopsy needle is pushed along the
guide, through the wall of the rectum and into the
prostate. The needle is rotated gently, prostate tissue
samples are collected and the needle withdrawn. When
an ultrasound probe is used to guide the needle, the
procedure is called a transrectal ultrasound-guided
biopsy, or TRUS.
Cytoscopy
For this procedure, the patient is given either a
general or a local anesthetic. An instrument called a
cytoscope (a thin-lighted tube with telescopic lenses) is
passed through the urethra. By looking through the
cytoscope, the doctor can see if there is any blockage in
the urethra and remove it. Tissue samples from the
urinary bladder or the prostate can be collected for
microscopic examination.
This test is generally performed in an operating
room or in a physician’s office. An hour before the
procedure, the patient is given a sedative to help him
relax. An intravenous (IV) line will be placed in a vein
in the arm to give medications and fluids if necessary.
The patient is asked to lie on a special table with his
knees apart and stirrups are used to support his feet
and thighs. The genital area is cleansed with an antiseptic solution. If general anesthesia is being used, the
patient is given the medication through the IV tube or
inhaled gases or both. If a local anesthetic is being
used, the anesthetic solution is gently instilled into
the urethra.
After the area is numb, a cytoscope is inserted into
the urethra and slowly pushed into the prostate. Tiny
forceps or scissors are inserted through the cytoscope
to collect small pieces of tissue that are used for
biopsy. The cytoscope is then withdrawn. The entire
procedure may take 30–45 minutes. Sometimes a
catheter (tube) is left in the urinary bladder to help
GALE ENCYCLOPEDIA OF MEDICINE

Alternate procedures
Many different tests can be performed to diagnose
prostate diseases and cancer. A routine screening test
called digital rectal examination (DRE) can identify
any lumps or abnormality with the prostate. Blood
tests that measure the levels of certain protein markers, such as PSA, can indicate the presence of prostate cancer cells. X rays and other imaging techniques
(such as computed tomography scans, magnetic resonance imaging, and ultrasonograms), where detailed
pictures of areas inside the body are put together by a
computer, can also be used to determine the extent and
spread of the disease. However, a prostate biopsy and
examination of the cells under a microscope remains
the most definitive test for diagnosing and grading
prostate cancer.

Preparation
Before scheduling the biopsy, the doctor should
be made aware of all the medications that the patient is
taking, if the patient is allergic to any medication, and
if he has any bleeding problems. The patient may be
given an antibiotic shortly before the test to reduce the
risk of any infection afterwards. If the biopsy is done
through the perineum, there are no special preparations. If it is being done through the rectum, the
patient is asked to take an enema and is instructed
on how to do it.
If a cytoscopy is being performed, the patient is
asked to sign a consent form. The patient is also asked
to take antibiotics before and for several days after the
test to prevent infection due to insertion of the instruments. If a general anesthetic is going to be used, food
and liquids will be restricted for at least eight hours
before the test.

Aftercare

general anesthesia is used, the patient is taken to the
recovery room and kept there until he wakes up and is
able to walk. He is allowed food and liquids after he
wakes up. After general anesthesia, the patient may
experience some tiredness and aching of the muscles
throughout the body. If local anesthesia was administered, there is a brief burning sensation and a
strong urge to urinate when the cytoscope is
removed.
After the procedure, it is common to experience
frequent urination with a burning sensation for a few
days. Drinking a lot of fluids will help reduce the burning sensation and the chances of an infection. There
may also be some blood in the urine. However, if blood
clots are seen, or if the patient is unable to pass urine
eight hours after the cytoscopy, the doctor should be
notified. In addition, if the patient develops a high
fever, and complains of chills or abdominal pain after
the procedure, he should see the doctor right away.
Although serious infections are rare, a few patients
develop such severe illnesses as meningitis following a
prostate biopsy.

Risks
Prostate biopsy performed with a needle is a lowrisk procedure. The possible complications include
some bleeding into the urethra, bleeding from the
rectum, an infection, a temporarily lowered sperm
count, or an inability to urinate. These complications
are treatable and the doctor should be notified of
them.
Cytoscopy is generally a very safe procedure. The
most common complication is an inability to urinate
due to a swelling of the urethra. A catheter (tube) may
have to be inserted to help drain out the urine. If there
is an infection after the procedure, antibiotics are
given to treat it. In very rare instances, the urethra or
the urinary bladder may be perforated because of the
insertion of the instrument. If this complication
occurs, surgery may be needed to repair the damage.

Following a needle biopsy, the patient may experience some pain and discomfort. He should avoid strenuous activities for the rest of the day. He may also
notice some blood in his urine for two to three days
after the test and some amount of rectal bleeding. If
there is persistent bleeding, pain, or fever, and if the
patient is unable to urinate for 24 hours, the doctor
should be notified immediately.

If the prostate tissue samples show no sign of
inflammation, and if no cancerous cells are detected,
the results are normal.

When a cytoscopy is performed under a local
anesthetic, the patient is asked to lie down for 30
minutes after the test and is then allowed to go. If

Analysis of the prostate tissue under the microscope reveals any abnormalities. In addition, the presence of cancerous cells can be detected. If a tumor is

GALE ENCYCLOPEDIA OF MEDICINE

Normal results

Abnormal results

3045

Prostate biopsy

the urine drain out, until the swelling in the urethra has
subsided.

Prostate biopsy

KEY TERMS
Benign prostatic hyperplasia (BPH)—A noncancerous condition of the prostate that causes overgrowth of the prostate tissue, thus enlarging the
prostate and obstructing urination.
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Computed tomography (CT) scan—A medical procedure in which a series of x rays are taken and put
together by a computer in order to form detailed
pictures of areas inside the body.
Digital rectal examination—A routine screening
test that is used to detect any lumps in the prostate
gland or any hardening or other abnormality of the
prostate tissue. The doctor inserts a gloved and
lubricated finger (digit) into the patient’s rectum,
which lies just behind the prostate. Typically, since
a majority of tumors develop in the posterior region
of the prostate, they can be detected through the
rectum.
Magnetic resonance imaging (MRI)—A medical
procedure used for diagnostic purposes where pictures of areas inside the body are created using a
magnet linked to a computer.
Pathologist—A doctor who specializes in the diagnosis of disease by studying cells and tissues under
a microscope.
Ultrasonogram—A procedure in which highfrequency sound waves that cannot be heard by
human ears are bounced off internal organs and
tissues. These sound waves produce a pattern of
echoes that are then used by the computer to
create sonograms or pictures of areas inside the
body.
Urethra—The tube that carries the urine from the
urinary bladder and (in males) the semen from the
sex glands to the outside of the body.

present, the pathologist ‘‘grades’’ the tumor, in order
to estimate how aggressive the tumor is. The most
commonly used grading system is called the
‘‘Gleason system.’’
Normal prostate tissue has certain characteristic
features that the cancerous tissue lacks. In the Gleason
system, prostate cancers are graded by how closely
they resemble normal prostate tissue. The system
assigns a grade ranging from 1 to 5. The grades
3046

assigned to two areas of cancer are added up for a
combined score that is between 2 and 10. A score
between 2 and 4 is called low and implies that the
cancer is a slow-growing one. A Gleason score of 8
to 10 is high and indicates that the cancer is aggressive.
The higher the Gleason score, the more likely it is that
the cancer is fast-growing and may have already
grown out of the prostate and spread to other areas
(metastasized).
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Prostate Cancer.’’ In The Merck Manual of Diagnosis
and Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Adamakis, I., D. Mitropoulos, K. Haritopoulos, et al.
‘‘Pain During Transrectal Ultrasonography Guided
Prostate Biopsy: A Randomized Prospective Trial
Comparing Periprostatic Infiltration with Lidocaine
with the Intrarectal Instillation of Lidocaine-Prilocain
Cream.’’ World Journal of Urology 20 (December
2003): E-pub.
Hsieh, K., and P. C. Albertsen. ‘‘Populations at High Risk
for Prostate Cancer.’’ Urological Clinics of North
America 30 (November 2003): 669–676.
Jones, J. S., and C. D. Zippe. ‘‘Rectal Sensation Test Helps
Avoid Pain of Apical Prostate Biopsy.’’ Journal of
Urology 170 (December 2003): 2316–2318.
Meisel, F., C. Jacobi, R. Kollmar, et al. ‘‘Acute
Meningitis after Transrectal Prostate Biopsy.’’ [in
German] Der Urologe: Ausg. A 42 (December 2003):
1611–1615.
Seitz, C., S. Palermo, and B. Djavan. ‘‘Prostate Biopsy.’’
Minerva Urologica Nefrologica 55 (December 2003):
205–218.
Shetty, Sugandh, MD. ‘‘Transrectal Ultrasound of the
Prostate (TRUS).’’ eMedicine March 1, 2004. <http://
www.emedicine.com/med/topic3477.htm>.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
American Urologic Association. 1120 N. Charles St.,
Baltimore, MD 21201. (410) 223-4310.
National Prostate Cancer Coalition. 1300 19th Street NW,
Suite 400, Washington, DC 20036. (202) 842-3600
ext. 214.
Prostate Cancer InfoLink. <http://www.comed.com/
Prostate/index.html>.

Lata Cherath, PhD
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Prostate cancer is a disease in which cells in the
prostate gland become abnormal and start to grow
uncontrollably, forming tumors.

Description
Prostate cancer is a malignancy of one of the
major male sex glands. Along with the testicles and
the seminal vesicles, the prostate secretes the fluid that
makes up semen. The prostate is about the size of a
walnut and lies just behind the urinary bladder. A
tumor in the prostate interferes with proper control
of the bladder and normal sexual functioning. Often
the first symptom of prostate cancer is difficulty in
urinating. However, because a very common, noncancerous condition of the prostate, benign prostatic
hyperplasia (BPH), also causes the same problem,
difficulty in urination is not necessarily due to cancer.
Cancerous cells within the prostate itself are generally not deadly on their own. However, as the tumor
grows, some of the cells break off and spread to other
parts of the body through the lymph or the blood, a
process known as metastasis. The most common sites
for prostate cancer to metastasize are the seminal
vesicles, the lymph nodes, the lungs, and various
bones around the hips and the pelvic region. The
effects of these new tumors are what can cause death.
As of the early 2000s, prostate cancer is the most
commonly diagnosed malignancy among adult males
in Western countries. Although prostate cancer is
often very slow growing, it can be aggressive, especially in younger men. Given its slow growing nature,
many men with the disease die of other causes rather
than from the cancer itself.
Prostate cancer affects African-American men
twice as often as white men; the mortality rate
among African-Americans is also two times higher.
African-Americans have the highest rate of prostate
cancer of any world population group.

Causes and symptoms
The precise cause of prostate cancer is not known
as of the early 2000s. However, there are several
known risk factors for disease including age over 55,
African-American heritage, a family history of the
disease, occupational exposure to cadmium or rubber,
and a high fat diet. Men with high plasma testosterone
GALE ENCYCLOPEDIA OF MEDICINE

Frequently, prostate cancer has no symptoms and
the disease is diagnosed when the patient goes for a
routine screening examination. However, when the
tumor is big or the cancer has spread to the nearby
tissues, the following symptoms may be seen:


weak or interrupted flow of the urine



frequent urination (especially at night)



difficulty starting urination



inability to urinate



pain or burning sensation when urinating



blood in the urine



persistent pain in lower back, hips, or thighs (bone
pain)



painful ejaculation

Diagnosis
Prostate cancer is curable when detected early.
Yet the early stages of prostate cancer are often
asymptomatic, so the disease often goes undetected
until the patient has a routine physical examination.
Diagnosis of prostate cancer can be made using some
or all of the following tests.
Digital rectal examination (DRE)
In order to perform this test, the doctor puts a
gloved, lubricated finger (digit) into the rectum to feel
for any lumps in the prostate. The rectum lies just
behind the prostate gland, and a majority of prostate
tumors begin in the posterior region of the prostate. If
the doctor does detect an abnormality, he or she may
order more tests in order to confirm these findings.
Blood tests
Blood tests are used to measure the amounts of
certain protein markers, such as prostate-specific antigen
(PSA), found circulating in the blood. The cells lining the
prostate generally make this protein and a small amount
can be detected normally in the bloodstream. In contrast,
prostate cancers produce a lot of this protein, significantly raising the circulating levels. A finding of a PSA
level higher than normal for the patient’s age group therefore suggests that cancer is present.
Transrectal ultrasound
A small probe is placed in the rectum and sound
waves are released from the probe. These sound waves
3047

Prostate cancer

Prostate cancer

levels may also have an increased risk for developing
prostate cancer.

Prostate cancer

bounce off the prostate tissue and an image is created.
Since normal prostate tissue and prostate tumors
reflect the sound waves differently, the test is an efficient and accurate way to detect tumors. Though the
insertion of the probe into the rectum may be slightly
uncomfortable, the procedure is generally painless and
takes only 20 minutes.
Prostate biopsy
If cancer is suspected from the results of any of the
above tests, the doctor will remove a small piece of
prostate tissue with a hollow needle. This sample is
then checked under the microscope for the presence of
cancerous cells. Prostate biopsy is the most definitive
diagnostic tool for prostate cancer.
Prostate cancer can also be diagnosed based on
the examination of the tissue removed during a transurethral resection of the prostate (TURP). This procedure is performed to help alleviate the symptoms of
BPH, a benign enlargement of the prostate. Like a
biopsy, this is a definitive diagnostic method for prostate cancer.
X rays and imaging techniques
A chest x ray may be ordered to determine
whether the cancer has spread to the lungs. Imaging
techniques (such as computed tomography scans (CT)
and magnetic resonance imaging (MRI)), where a computer is used to generate a detailed picture of the
prostate and areas nearby, may be done to get a clearer
view of the internal organs. A bone scan may be used
to check whether the cancer has spread to the bone.

Treatment
Once cancer is detected during the microscopic
examination of the prostate tissue during a biopsy or
TURP, doctors will determine two different numerical
scores that will help define the patient’s treatment and
prognosis.
Tumor grading
Initially, the pathologist will grade the tumor
based on his or her examination of the biopsy tissue.
The pathologist scores the appearance of the biopsy
sample using the Gleason system. This system uses a
scale of one to five based on the sample’s similarity or
dissimilarity to normal prostate tissue. If the tissue is
very similar to normal tissue, it is still well differentiated and given a low grading number, such as one or
two. As the tissue becomes more and more abnormal
(less and less differentiated), the grading number
3048

increases, up to five. Less differentiated tissue is considered more aggressive and more likely to be the
source of metastases.
The Gleason grading system is best predictive of
the prognosis of a patient if the pathologist gives two
scores to a particular sample—a primary and a secondary pattern. The two numbers are then added
together and that is the Gleason score reported to the
patient. Thus, the lowest Gleason score available is
two (a primary and secondary pattern score of one
each). A typical Gleason score is five (which can be a
primary score of two and a secondary score of three or
visa-versa). The highest score available is 10, with a
pure pattern of very undifferentiated tissue, that is, of
grade five. The higher the score, the more abnormal
behavior of the tissue, the greater the chance for
metastases, and the more serious the prognosis after
surgical treatment. A study found that the ten-year
cancer survival rate without evidence of disease for
grade two, three, and four cancers is 94% of patients.
The rate is 91% for grade five cancers, 78% for grade
six, 46% for grade seven, and 23% for grade eight,
nine, and ten cancers.
Cancer staging
The second numeric score determined by the doctor will be the stage of the cancer, which takes into
account the grade of the tumor determined by the
pathologist. Based on the recommendations of the
American Joint Committee on Cancer (AJCC), two
kinds of data are used for staging prostate cancer.
Clinical data are based on the external symptoms of
the cancer, while histopathological data is based on
surgical removal of the prostate and examination of its
tissues. Clinical data are most useful to make treatment decisions, while pathological data is the best
predictor of prognosis. For this reason, the staging
of prostate cancer takes into account both clinical
and histopathologic information. Specifically, doctors
look at tumor size (T), lymph node involvement (N),
the presence of visceral (internal organ) involvement
(metastasis = M), and the grade of the tumor (G).
The classification of tumor as T1 means the cancer
that is confined to the prostate gland and the tumor
that is too small to be felt during a DRE. T1 tumors
are often found after examination of tissue removed
during a TURP. The T1 definition is subdivided into
those cancers that show less than 5% cancerous cells in
the tissue sample (T1a) or more than 5% cancerous
cells in the tissue sample (T1b). T1c means that the
biopsy was performed based on an elevated PSA
result. The second tumor classification is T2, where
the tumor is large enough to be felt during the DRE.
GALE ENCYCLOPEDIA OF MEDICINE

With a T3 tumor the cancer has spread to the
connective tissue near the prostate (T3a) or to the
seminal vesicles as well (T3b). T4 indicates that cancer
has spread within the pelvis to tissue next to the prostate such as the bladder’s sphincter, the rectum, or the
wall of the pelvis. Prostate cancer tends to spread next
into the regional lymph nodes of the pelvis, indicated
as N1. Prostate cancer is said to be at the M1 stage
when it has metastasized outside the pelvis in distant
lymph nodes (M1a), bone (M1b) or organs such as the
liver or the brain (M1c). Pain, weight loss, and fatigue
often accompany the M1 stage.
The grade of the tumor (G) can assessed during a
biopsy, TURP surgery, or after removal of the prostate. There are three grades recognized: G1, G2, and
G3, indicating the tumor is well, moderately, or poorly
differentiated, respectively. The G, LN, M descriptions are combined with the T definition to determine
the stage of the prostate cancer.
Stage I prostate cancer comprises patients that are
T1a, N0, M0, G1. Stage II includes a variety of condition combinations including T1a, N0, M0, G2, 3 or
4; T1b, N0, M0, Any G; T1c, N0, M0, Any G; T1, N0,
M0, Any G or T2, N0, M0, Any G. The prognosis for
cancers at these two stages is very good. For men
treated with stage I or stage II disease, over 95% are
alive after five years.
Stage III prostate cancer occurs when conditions
are T3, N0, M0, any G. Stage IV is T4, N0, M0, any G;
any T, N1, M0, any G; or any T, any N, M1, Any G.
Although the cancers of Stage III are more advanced,
the five year prognosis is still good, with 70% of men
diagnosed at these stage still living. The spread of the
cancer into the pelvis (T4), lymph (N1), or distant
locations (M1) are very significant events, as the five
year survival rate drops to 30% for Stage IV.
Treatment options
The doctor and the patient will decide on the
treatment mode after considering many factors. For
example, the patient’s age, the stage of the disease, his
general health, and the presence of any co-existing
illnesses have to be considered. In addition, the
patient’s personal preferences and the risks and benefits of each treatment protocol are also taken into
account before any decision is made.
SURGERY. For stage I and stage II prostate cancer,
surgery is the most common method of treatment
because it theoretically offers the chance of completely

GALE ENCYCLOPEDIA OF MEDICINE

removing the cancer from the body. Radical prostatectomy involves complete removal of the prostate.
The surgery can be done using a perineal approach,
where the incision is made between the scrotum and
the anus, or using a retropubic approach, where the
incision is made in the lower abdomen. Perineal
approach is also known as nerve-sparing prostatectomy, as it is thought to reduce the effect on the nerves
and thus reduce the side effects of impotence and
incontinence. However, the retropubic approach
allows for the simultaneous removal of the pelvic
lymph nodes, which can give important pathological
information about the tumor spread.
The drawback to surgical treatment for early
prostate cancer is the significant risk of side effects
that impact the quality of life of the patient. Even
using nerve-sparing techniques, studies run by the
National Cancer Institute (NCI) found that 60–80%
of men treated with radical prostatectomy reported
themselves as impotent (unable to achieve an erection
sufficient for sexual intercourse) two years after surgery. This side effect can be sometimes countered by
prescribing sildenafil citrate (Viagra). Furthermore,
8% to 10% of patients were incontinent in that time
span. Despite the side effects, the majority of men were
reported as satisfied with their treatment choice.
Additionally, there is some evidence that the skill
and the experience of the surgeon are central factors
in the ultimate side effects seen.
A second method of surgical treatment of prostate
cancer is cryosurgery. Guided by ultrasound, surgeons
insert up to eight cryoprobes through the skin and into
close proximity with the tumor. Liquid nitrogen (temperature of -320.8 o F, or -196o C) is circulated
through the probe, freezing the tumor tissue. In prostate surgery, a warming tube is also used to keep the
urethra from freezing. Patients currently spend a day
or two in the hospital following the surgery, but it
could be an outpatient procedure in the near future.
Recovery time is about one week. Side effects have
been reduced in recent years, although impotence still
affects almost all who have had cryosurgery for prostate cancer. Cryosurgery is considered a good alternative for those too old or sick to have traditional
surgery or radiation treatments or when these more
traditional treatments are unsuccessful. There is a limited amount of information about the long-term efficacy of this treatment for prostate cancer.
Radiation therapy
Radiation therapy involves the use of high-energy
x rays to kill cancer cells or to shrink tumors. It can be
used instead of surgery for stage I and II cancer. The
3049

Prostate cancer

T2a indicates that only the left or the right side of the
gland is involved, while T2b means both sides of the
prostate gland has tumor.

Prostate cancer

radiation can either be administered from a machine
outside the body (external beam radiation), or small
radioactive pellets can be implanted in the prostate
gland in the area surrounding the tumor, called brachytherapy or interstitial implantation. Pellets containing radioactive iodine (I-125), palladium (Pd
103), or iridium (Ir 192) can be implanted on an outpatient basis, where they remain permanently. The
radioactive effect of the seeds last only about a year.
The side effects of radiation can include inflammation of the bladder, rectum, and small intestine as
well as disorders of blood clotting (coagulopathies).
Impotence and incontinence are often delayed side
effects of the treatment. A study indicated that bowel
control problems were more likely after radiation therapy when compared to surgery, but impotent and
incontinence were more likely after surgical treatment.
Long-term results with radiation therapy are dependent on stage. A review of almost 1000 patients treated
with megavoltage irradiation showed 10 year survival
rates to be significantly different by T-stage: T1 (79%),
T2 (66%), T3 (55%), and T4 (22%). There does not
appear to be a large difference in survival between
external beam or interstitial treatments.
HORMONE THERAPY. Hormone therapy is commonly used when the cancer is in an advanced stage
and has spread to other parts of the body, such as stage
III or stage IV. Prostate cells need the male hormone
testosterone to grow. Decreasing the levels of this
hormone or inhibiting its activity will cause the cancer
to shrink. Hormone levels can be decreased in several
ways. Orchiectomy is a surgical procedure that
involves complete removal of the testicles, leading to
a decrease in the levels of testosterone. Another
method tricks the body by administering the female
hormone estrogen. When estrogen is given, the body
senses the presence of a sex hormone and stops making
the male hormone testosterone. However, there are
some unpleasant side effects to hormone therapy.
Men may have ‘‘hot flashes,’’ enlargement and tenderness of the breasts, or impotence and loss of sexual
desire, as well as blood clots, heart attacks, and strokes,
depending on the dose of estrogen. Another side effect
is osteoporosis, or loss of bone mass leading to brittle
and easily fractured bones.
WATCHFUL WAITING. Watchful waiting means no
immediate treatment is recommended, but doctors
keep the patient under careful observation. This is
often done using periodic PSA tests. This option
is generally used in older patients when the tumor is
not very aggressive and the patients have other, more
life-threatening, illnesses. Prostate cancer in older men
tends to be slow-growing. Therefore, the risk of the

3050

patient dying from prostate cancer, rather than from
other causes, is relatively small.
Treatments for prostate cancer that are under
investigation in the early 2000s include evaluation of
combination therapies, such as postoperative radiation delivery, use of cytotoxic agents, and hormonal
treatment using luteinizing hormone-releasing hormone (LHRH) agonists and/or antiandrogens to
shut down the growth of the hormone-dependent
tumors. Other drugs that are being tested as of 2003
are chemoprotective agents like amifostine (Ethyol),
which are given to prostate cancer patients to counteract the harmful side effects of radiation treatment.

Alternative treatment
Alternative treatments that have been found helpful in coping with the emotional stress associated with
prostate cancer include meditation, guided imagery,
and relaxation techniques. Acupuncture is effective in
relieving pain in some patients.
A variety of herbal products have been used to
treat prostate cancer, including various compounds
used in traditional Chinese medicine as well as single
agents like Reishi mushrooms (Ganoderma lucidum).
One herbal compound that was under investigation by
the National Center for Complementary and
Alternative Medicine (NCCAM) as a possible treatment for prostate cancer was PC-SPES, a mixture of
eight herbs adapted from traditional Chinese medicine. In the summer of 2002, however, NCCAM put
its studies of PC-SPES on hold when the Food and
Drug Administration (FDA) determined that samples
of the product were contaminated with undeclared
prescription drug ingredients. PC-SPES was withdrawn from the American market in late 2002.

Prevention
Because the cause of the cancer is not known,
there is no definite way to prevent prostate cancer.
Given its common occurrence and the low cost of
screening, the American Cancer Society (ACS) and
the National Comprehensive Cancer Network
(NCCN) recommends that all men over age 40 have
an annual rectal examination and that men have an
annual PSA test beginning at age 50. AfricanAmerican men and men with a family history of prostate cancer, who have a higher than average risk,
should begin annual PSA testing even earlier, starting
at age 45.
However, mandatory screening for prostate cancer is controversial. Because the cancer is so slow
GALE ENCYCLOPEDIA OF MEDICINE

Antiandrogen—A substance that blocks the action
of androgens, the hormones responsible for male
characteristics. Used to treat prostate cancers that
require male hormones for growth.
Benign prostatic hyperplasia (BPH)—A noncancerous swelling of the prostate.
Brachytherapy—A method of treating cancers,
such as prostate cancer, involving the implantation
near the tumor of radioactive seeds.
Gleason grading system—A method of predicting
the tendency of a tumor in the prostate to metastasize based on how similar the tumor is to normal
prostate tissue.
Granulocyte/macrophage colony stimulating factor (GM-CSF)—A substance produced by cells of
the immune system that stimulates the attack upon
foreign cells. Used to treat prostate cancers as a
genetically engineered component of a vaccine
that stimulates the body to attack prostate tissue.
Histopathology—The study of diseased tissues at a
minute (microscopic) level.
Luteinizing hormone releasing hormone (LHRH)
agonist—A substance that blocks the action of
LHRH, a hormone that stimulates the production
of testosterone (a male hormone) in men. Used to
treat prostate cancers that require testosterone for
growth.
Orchiectomy—Surgical removal of the testes that
eliminates the production of testosterone to treat
prostate cancer.
Radical prostatectomy—Surgical removal of the
entire prostate, a common method of treating prostate cancer.
Prostate-specific antigen—A protein made by the
cells of the prostate that is increased by both BPH
and prostate cancer.
Transurethral resection of the prostate (TURP)—
Surgical removal of a portion of the prostate
through the urethra, a method of treating the symptoms of an enlarged prostate, whether from BPH or
cancer.

growing, and the side effects of the treatment can have
significant impact on patient quality of life, some
medical organizations question the wisdom of yearly
exams. Some organizations have even noted that the
effect of screening is discovering the cancer at an early
GALE ENCYCLOPEDIA OF MEDICINE

stage when it may never grow to have any outward
effect on the patient during their lifetime.
Nevertheless, the NCI reports that the current aggressive screening methods have achieved a reduction in
the death rate of prostate cancer of about 2.3% for
African-Americans and about 4.6% for Caucasians
since the mid-1990s, with a 20% increase in overall
survival rate during that period.
A low-fat diet may slow the progression of prostate cancer. To reduce the risk or progression of prostate cancer, the American Cancer Society recommends
a diet rich in fruits, vegetables and dietary fiber, and
low in red meat and saturated fats.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Prostate Cancer.’’ In The Merck Manual of Diagnosis
and Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Carroll, Peter R., et al. ‘‘Cancer of the Prostate.’’ In Cancer
Principles and Practice of Oncology, edited by Vincent
T. DeVita, et al. Philadelphia: Lippincott Williams &
Wilkins, 2001.
Wainrib, Barbara R., and Sandra Haber. Men, Women, and
Prostate Cancer. Oakland, CA: New Harbinger
Productions, Inc., 2000.
PERIODICALS

Alimi, D., C. Rubino, E. Pichard-Leandri, et al. ‘‘Analgesic
Effect of Auricular Acupuncture for Cancer Pain: A
Randomized, Blinded, Controlled Trial.’’ Journal of
Clinical Oncology 21 (November 15, 2003): 4120–4126.
Chang, S. S. ‘‘Exploring the Effects of Luteinizing HormoneReleasing Hormone Agonist Therapy on Bone Health:
Implications in the Management of Prostate Cancer.’’
Urology 62 (December 22, 2003): 29–35.
de la Fouchardiere, C., A. Flechon, and J. P. Droz.
‘‘Coagulopathy in Prostate Cancer.’’ Netherlands
Journal of Medicine 61 (November 2003): 347–354.
Dziuk, T., and N. Senzer. ‘‘Feasibility of Amifostine
Administration in Conjunction with High-Dose Rate
Brachytherapy.’’ Seminars in Oncology 30 (December
2003): 49–57.
Hsieh, K., and P. C. Albertsen. ‘‘Populations at High Risk
for Prostate Cancer.’’ Urological Clinics of North
America 30 (November 2003): 669–676.
Linares, L. A., and D. Echols. ‘‘Amifostine and External
Beam Radiation Therapy and/or High-Dose Rate
Brachytherapy in the Treatment of Localized Prostate
Carcinoma: Preliminary Results of a Phase II Trial.’’
Seminars in Oncology 30 (December 2003): 58–62.
Sliva, D. ‘‘Ganoderma lucidum (Reishi) in Cancer
Treatment.’’ Integrative Cancer Therapies 2 (December
2003): 358–364.
Spetz, A. C., E. L. Zetterlund, E. Varenhorst, and M.
Hammar. ‘‘Incidence and Management of Hot Flashes
3051

Prostate cancer

KEY TERMS

Prostate-specific antigen test

in Prostate Cancer.’’ Journal of Supportive Oncology 1
(November-December 2003): 263–273.
Wilson, S. S., and E. D. Crawford. ‘‘Prostate Cancer
Update.’’ Minerva Urologica e Nefrologica 55
(December 2003): 199–204.
ORGANIZATIONS

Association for the Cure of Cancer of the Prostate
(CaPCure). 1250 Fourth St., Suite 360, Santa Monica,
CA 90401. (800) 757-CURE.
<http://www.capcure.org>.
National Cancer Institute. Building 31, Room 10A31 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 4-CANCER. <http://cancernet.nci.nih.gov>.
National Center for Complementary and Alternative
Medicine (NCCAM) Clearinghouse. P. O. Box 7923,
Gaithersburg, MD 20898. (888) 644-6226.
<http://nccam.nih.gov>.
OTHER

FDA MedWatch Safety Alert for PC-SPES, SPES, updated
September 20, 2002. <http://www.fda.gov/medwatch/
SAFETY/2002/safety02.htm#spes>.
National Center for Complementary and Alternative
Medicine (NCCAM). Recall of PC-SPES and SPES
Dietary Supplements. NCCAM Publication No. D149,
September 2002. <http://nccam.nih.gov/health/alerts/
spes/index.htm>.

Lata Cherath, PhD
Michelle Johnson, M.S., J.D.
Rebecca J. Frey, PhD

Prostate gland removal see Prostatectomy
Prostate sonogram see Prostate ultrasound

Prostate-specific antigen test
Definition
Prostate-specific antigen, or PSA, is a protein
produced by the prostate gland that may be found in
elevated levels in the blood when a person develops
certain diseases of the prostate, notably prostate cancer. PSA is specific, because it is present only in prostate tissue. It is not specific for prostate cancer,
however, as it may also be elevated in men with benign
enlargement of this organ. The PSA test has been
called the ‘‘male PAP test.’’

Purpose
The blood test for PSA is used to screen older men
to detect prostate cancer at an early stage, and also to
3052

monitor its response to treatment. After lung cancer,
prostate cancer is the most common form of cancer in
men in the United States. Any routine physical exam
of a man aged 50 and older should include a digital
rectal examination (DRE), in which the doctor’s finger
probes the surface of the prostate gland to detect any
suspicious area of hardness or a tumor mass. If the
examination suggests that a tumor may in fact be
present or if the examiner is uncertain the logical
next step is a PSA test. If the PSA test is positive, a
sample of prostate tissue (biopsy) may be taken to
confirm that cancer is present. If negative, the test
may be repeated immediately to confirm the diagnosis,
or repeated the next year. Many physicians today
routinely do both a DRE and a PSA test each year
on their older male patients, so that, if cancer does
develop, it will be found at an early stage will be easier
to treat. The combination of a DRE and a PSA test
can detect approximately 80% of all prostate cancers.
At present, the PSA test is widely accepted as a
way of telling whether a patient with definite cancer is
responding to treatment. Because only the prostate
produces PSA, its presence in the blood following
complete removal of the prostate (radical prostatectomy) indicates that some cancer has been left behind.

Precautions
There is no physical reason not to do a PSA test.
Although, the level of PSA usually is elevated in men
with prostate cancer, it also may be abnormally high
(though usually not as high) in men with non-cancerous enlargement of the prostate (benign prostatic
hyperplasia or BPH). If thousands of men have the
PSA test routinely each year, many of them will have
unnecessary tests (such as biopsy or an ultrasound
study) to confirm cancer. If a ‘‘false-positive’’ result
is obtained, where the PSA level seems high but really
is not, some men may even be treated for prostate
cancer when no cancer is present. Both the American
Cancer Society and the American Urological
Association urge annual PSA testing to detect early
cancers, but the National Cancer Institute does not.

Description
The PSA test is a radioimmunoassay. Any antigen
causes the body to produce antibodies in an attempt to
neutralize or eliminate the antigen, often a substance
that harms body tissues. In the laboratory, a sample
of the patient’s blood is exposed to the antibody against
PSA, so that the amount of antigen (PSA) can be measured. The results generally are available the next day.
GALE ENCYCLOPEDIA OF MEDICINE

Antibody—A substance formed in the body in reaction to some foreign material invading the body, or
sometimes to diseased body tissue such as prostate
cancer. An antibody also may be prepared in the
laboratory and used to measure the amount of antigen in the blood.
Antigen—Either a foreign substance such as a virus
or bacterium, or a protein produced by diseased or
injured body tissue.
Biopsy—A procedure using a hollow needle to
obtain a small sample of tissue, such as from the
prostate. Often done to determine whether cancer
is present.
BPH—Benign prostatic hyperplasia, a noncancerous disorder that causes the prostate to enlarge.

Preparation
No special measures are needed when doing a
PSA test other than taking the usual precautions to
prevent infection at the needle puncture site.

Normal results
Each laboratory has its own normal range for
PSA. In fact, they may redefine the normal range
whenever starting to use a new batch of test chemicals.

Abnormal results
Some experts believe that more than 90% of men
with prostate cancer will have an elevated PSA level.
Others claim that as many as one-third of cancers
will be missed. The amount of PSA in the blood
drops when cancer is successfully treated, but rises
again if the tumor recurs, especially if it spreads to
other parts of the body. A new variation of the PSA
test shows how much of the material is bound to
other protein in the blood and how much is ‘‘free.’’
This procedure may be more accurate and could well
indicate whether either prostate cancer or BPH is
present.
Resources
ORGANIZATIONS

Prostate Health Council, American Foundation for
Urologic Disease. 1128 N. Charles St., Baltimore, MD
21201.
GALE ENCYCLOPEDIA OF MEDICINE

Prostate Health Council Important Information
AboutProstate-Specific Antigen (PSA). American
Foundation for Urologic Disease, 1128 N.Charles St.,
Baltimore, MD 21201.

David A. Cramer, MD

Prostate ultrasound
Definition
A prostate ultrasound is a diagnostic test used to
detect potential problems with a man’s prostate. An
ultrasound test uses very high frequency sound waves
that are passed through the body. The pattern of
reflected sound waves, or ‘‘echoes,’’ shows the outline
of the prostate. This test can show whether the prostate is enlarged, and whether an abnormal growth that
might be cancer is present.

Purpose
The prostate is a chestnut-shaped organ surrounding the beginning of the urethra in men. It produces a milky fluid that is part of the seminal fluid
discharged during ejaculation. The prostate can
become enlarged, particularly in men over age 50.
Also, cancer of the prostate can develop, which tends
to affect older men.
During a physical examination, a doctor may
perform a digital rectal examination. In this examination, the doctor uses a gloved and lubricated finger
inserted in the rectum to feel for any abnormalities. If
this examination shows that the prostate is enlarged
or a hard lump is present, an ultrasound may be
done. Another reason a doctor might perform an
ultrasound is if a blood test shows abnormal levels
of a substance called prostate-specific antigen (PSA).
Abnormal levels of PSA may indicate the presence of
cancer.
If there is a suspicious lump, the doctor will want
to take a sample of some of the tissue (prostate
biopsy) to test it to see whether it is in fact cancer.
Doing an ultrasound first will show the doctor what
part of the prostate should be taken as a sample.
Ultrasound can also show whether cancerous tissue
is still only within the prostate or whether it has
begun to spread to other locations. If prostate cancer
is present and the doctor decides to treat it with a
3053

Prostate ultrasound

OTHER

KEY TERMS

Prostate ultrasound

surgical freezing procedure, ultrasound is used as an
aid in the procedure.
An ultrasound can reveal other types of prostate
disease as well. For example, it can show if there is
inflammation of the prostate (prostatitis). Sometimes
it is used to learn why a man is unable to father
children (infertility).

Precautions
A prostate ultrasound study is generally not performed on men who have recently had surgery on their
lower bowel. This is because the test requires placing
an ultrasound probe about the size of a finger into the
rectum.

Description
Prostate ultrasound is generally done using a
technique called the transrectal method. This procedure can be done in an outpatient clinic. The cylinder-shaped ultrasound probe is gently placed in the
rectum as the patient lies on his left side with the
knees bent. The probe is rocked back and forth to
obtain images of the entire prostate. The procedure
takes about 15–25 minutes to perform. After the test,
the patient’s doctor can be notified right away, and
usually he or she will have a written report within 36
hours.

Preparation
To prepare for a prostate ultrasound, an enema is
taken two to four hours before the exam. The patient
should not urinate for one hour before the test. If
biopsies may be done, the doctor will prescribe an
antibiotic that usually is taken in four doses starting
the night before the biopsy, the morning of the test,
that evening, and the following morning.

Aftercare
There is some discomfort, but less than most
patients expect. In fact, worrying ahead of time is
usually the hardest part. Generally, the patient is
allowed to leave after a radiologist or urologist has
reviewed the results. There may be some mucus or a
small amount of bleeding from the rectum after the
ultrasound. Some patients notice a small amount of
blood in the urine for up to two days after the test.
Blood may also be present in the semen. As long as the
amount of blood is small, there is no cause for
concern.
3054

KEY TERMS
Benign prostatic hypertrophy (BPH)—Benign prostatic hypertrophy is an enlargement of the prostate
that is not cancerous. However, it may cause problems with urinating or other symptoms.
Prostate-specific antigen (PSA)—A substance that
often is produced by cancers of the prostate. It can
be detected in a blood test.
Urethra—The tube through which urine passes
from the bladder and is excreted to outside the
body.

Risks
There are no serious risks from a prostate ultrasound study. Infection is rare and probably is a result
of biopsy rather than the sonogram itself. If the ultrasound probe is moved too vigorously, some bleeding
may continue for a few days.

Normal results
Modern ultrasound techniques can display both
the smooth-surfaced outer shell of the prostate and the
core tissues surrounding the urethra. The entire
volume of the prostate should be less than 20 milliliters, and its outline should appear as a smooth echoreflecting (echogenic) rim. Some irregularities within
the substance of the gland and calcium deposits are
normal findings.

Abnormal results
An enlarged prostate with dimmed echoes may
indicate either prostatitis or benign enlargement of
the gland, called benign prostatic hypertrophy
(BPH). A distinct lump of tissue more likely means
cancer. Cancer also often appears as an irregular area
within the gland that distorts the normal pattern of
echoes. In either case, a biopsy should clarify the
diagnosis.
Resources
ORGANIZATIONS

Prostate Health Council, American Foundation for
Urologic Disease. 1128 N. Charles St., Baltimore, MD
21201. 800-242-AFUD.

David A. Cramer, MD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Prostatectomy refers to the surgical removal of
part of the prostate gland (transurethral resection, a
procedure performed to relieve urinary symptoms
caused by benign enlargement), or all of the prostate
(radical prostatectomy, the curative surgery most
often used to treat prostate cancer).

Purpose
Benign disease
When men reach their mid-40s, the prostate gland
begins to enlarge. This condition, benign prostatic
hyperplasia (BPH) is present in more than half of
men in their 60s and as many as 90% of those over
90. Because the prostate surrounds the urethra, the
tube leading urine from the bladder out of the body,
the enlarging prostate narrows this passage and makes
urination difficult. The bladder does not empty completely each time a man urinates, and, as a result, he
must urinate with greater frequency, night and day. In
time, the bladder can overfill, and urine escapes from
the urethra, resulting in incontinence. An operation
called transurethral resection of the prostate (TURP)
relieves symptoms of BPH by removing the prostate
tissue that is blocking the urethra. No incision is
needed. Instead a tube (retroscope) is passed through
the penis to the level of the prostate, and tissue is either
removed or destroyed, so that urine can freely pass
from the body.
Malignant disease
Prostate cancer is the single most common form of
non-skin cancer in the United States and the most
common cancer in men over 50. Half of men over 70
and almost all men over the age of 90 have prostate
cancer, and the American Cancer Society estimates
that 198,000 new cases will be diagnosed in 2001.
This condition does not always require surgery. In
fact, many elderly men adopt a policy of ‘‘watchful
waiting,’’ especially if their cancer is growing slowly.
Younger men often elect to have their prostate gland
totally removed along with the cancer it contains—an
operation called radical prostatectomy. The two main
types of this surgery, radical retropubic prostatectomy
and radical perineal prostatectomy, are performed
only on patients whose cancer is limited to the prostate. If cancer has broken out of the capsule surrounding the prostate gland and spread in the area or to
distant sites, removing the prostate will not prevent
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Potential complications of TURP include bleeding, infection, and reactions to general or local
anesthesia. About one man in five will need to have
the operation again within 10 years.
Open (incisional) prostatectomy for cancer should
not be done if the cancer has spread beyond the prostate, as serious side effects may occur without the
benefit of removing all the cancer. If the bladder is
retaining urine, it is necessary to insert a catheter
before starting surgery. Patients should be in the best
possible general condition before radical prostatectomy. Before surgery, the bladder is inspected using an
instrument called a cystoscope to help determine the
best surgical technique to use, and to rule out other
local problems.

Description
TURP
This procedure does not require an abdominal
incision. With the patient under either general or
spinal anesthesia, a cutting instrument or heated wire
loop is inserted to remove as much prostate tissue as
possible and seal blood vessels. The excised tissue is
washed into the bladder, then flushed out at the end of
the operation. A catheter is left in the bladder for one
to five days to drain urine and blood. Advanced laser
technology enables surgeons to safely and effectively
burn off excess prostate tissue blocking the bladder
opening with fewer of the early and late complications
associated with other forms of prostate surgery. This
procedure can be performed on an outpatient basis,
but urinary symptoms do not improve until swelling
subsides several weeks after surgery.
Radical prostatectomy
RADICAL RETROPUBIC PROSTATECTOMY. This is a
useful approach if the prostate is very large, or cancer
is suspected. With the patient under general or spinal
anesthesia or an epidural, a horizontal incision is made
in the center of the lower abdomen. Some surgeons
begin the operation by removing pelvic lymph nodes
to determine whether cancer has invaded them, but
recent findings suggest there is no need to sample them
in patients whose likelihood of lymph node metastases
is less than 18%. A doctor who removes the lymph
nodes for examination will not continue the operation
if they contain cancer cells, because the surgery will

3055

Prostatectomy

Prostatectomy

the remaining cancer from growing and spreading
throughout the body.

Prostatectomy

not cure the patient. Other surgeons remove the prostate gland before examining the lymph nodes. A tube
(catheter) inserted into the penis to drain fluid from
the body is left in place for 14–21 days.
Originally, this operation also removed a thin rim
of bladder tissue in the area of the urethral sphincter—
a muscular structure that keeps urine from escaping
from the bladder. In addition, the nerves supplying the
penis often were damaged, and many men found
themselves impotent (unable to achieve erections)
after prostatectomy. A newer surgical method called
potency-sparing radical prostatectomy preserves sexual potency in 75% of patients and fewer than 5%
become incontinent following this procedure.
RADICAL PERINEAL PROSTATECTOMY. This procedure is just as curative as radical retropubic prostatectomy but is performed less often because it does not
allow the surgeon to spare the nerves associated with
erection or, because the incision is made above the
rectum and below the scrotum, to remove lymph
nodes. Radical perineal prostatectomy is sometimes
used when the cancer is limited to the prostate and
there is no need to spare nerves or when the patient’s
health might be compromised by the longer procedure. The perineal operation is less invasive than retropubic prostatectomy. Some parts of the prostate can
be seen better, and blood loss is limited. The absence of
an abdominal incision allows patients to recover more
rapidly. Many urologic surgeons have not been
trained to perform this procedure. Radical prostatectomy procedures last one to four hours, with radical
perineal prostatectomy taking less time than radical
retropubic prostatectomy. The patient remains in the
hospital three to five days following surgery and can
return to work in three to five weeks. Ongoing
research indicates that laparoscopic radical prostatectomy may be as effective as open surgery in treatment of early-stage disease.

disease. Recent studies have shown that total cryosurgery, which destroys the prostate, is at least as effective
as radical prostatectomy without the trauma of major
surgery.

Preparation
As with any type of major surgery done under
general anesthesia, the patient should be in optimal
condition. Most patients having prostatectomy are in
the age range when cardiovascular problems are frequent, making it especially important to be sure that
the heart is beating strongly, and that the patient is not
retaining too much fluid. Because long-standing prostate disease may cause kidney problems from urine
‘‘backing up,’’ it also is necessary to be sure that the
kidneys are working properly. If not, a period of
catheter drainage may be necessary before doing the
surgery.

Aftercare
Following TURP, a catheter is placed in the
bladder to drain urine and remains in place for two
to three days. A solution is used to irrigate the bladder and urethra until the urine is clear of blood,
usually within 48 hours after surgery. Whether antibiotics should be routinely given remains an open
question. Catheter drainage also is used after open
prostatectomy. The bladder is irrigated only if blood
clots block the flow of urine through the catheter.
Patients are given intravenous fluids for the first 24
hours, to ensure good urine flow. Patients resting in
bed for long periods are prone to blood clots in their
legs (which can pass to the lungs and cause serious
breathing problems). This can be prevented by elastic
stockings and by periodically exercising the patient’s
legs. The patient remains in the hospital one to two
days following surgery and can return to work in one
to two weeks.

Cryosurgery
Also called cryotherapy or cryoablation, this minimally invasive procedure uses very low temperatures
to freeze and destroy cancer cells in and around the
prostate gland. A catheter circulates warm fluid
through the urethra to protect it from the cold.
When used in connection with ultrasound imaging,
cryosurgery permits very precise tissue destruction.
Traditionally used only in patients whose cancer had
not responded to radiation, but now approved by
Medicare as a primary treatment for prostate cancer,
cryosurgery can safely be performed on older men, on
patients who are not in good enough general health to
undergo radical prostatectomy, or to treat recurrent
3056

Risks
The complications and side effects that may occur
during and after prostatectomy include:


Excessive bleeding, which in rare cases may require
blood transfusion.



Incontinence when, during retropubic prostatectomy, the muscular valve (sphincter) that keeps
urine in the bladder is damaged. Less common
today, when care is taken not to injure the sphincter.



Impotence, occurring when nerves to the penis are
injured during the retropubic operation. Today’s
GALE ENCYCLOPEDIA OF MEDICINE

BPH—Benign prostatic hypertrophy, a very common noncancerous cause of prostatic enlargement
in older men.
Catheter—A tube that is placed through the urethra
into the bladder in order to provide free drainage of
urine and blood following either TURP or open
prostatectomy.
Cryosurgery—In prostatectomy, the use of a very
low-temperature probe to freeze and thereby
destroy prostatic tissue.
Impotence—The inability to achieve and sustain
penile erections.
Incontinence—The inability to retain urine in the
bladder until a person is ready to urinate
voluntarily.
Prostate gland—The gland surrounding the male
urethra just below the base of the bladder. It
secretes a fluid that constitutes a major portion of
the semen.
Urethra—The tube running from the bladder to the
tip of the penis that provides a passage for eliminating urine from the body.

‘‘nerve-sparing’’ technique has drastically cut down
on this problem.


Some patients who receive a large volume of irrigating fluid after TURP develop high blood pressure,
vomiting, trouble with their vision, and mental confusion. This condition is caused by a low salt level in
the blood, and is reversed by giving salt solution.



A permanent narrowing of the urethra called a stricture occasionally develops when the urethra is
damaged during TURP.



There is about a 34% chance that the cancer will
recur within 10 years of the procedure. In addition,
about 25% of patients experience what is known as
biochemical recurrence, which means that the level of
prostate-specific antigen (PSA) in the patient’s blood
serum begins to rise rapidly. Recurrence of the tumor
or biochemical recurrence can be treated with radiation therapy or androgen deprivation therapy.

Normal results
In patients with BPH who have the TURP operation, urination should become much easier and less
frequent, and dribbling or incontinence should cease.
GALE ENCYCLOPEDIA OF MEDICINE

In patients having radical prostatectomy for cancer, a
successful operation will remove the tumor and prevent its spread to other areas of the body (metastasis).
If examination of lymph nodes shows that cancer
already had spread beyond the prostate at the time
of surgery, other measures are available to control the
tumor.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Prostate Cancer.’’ Section 17, Chapter 233 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2002.
Marks, Sheldon. Prostate Cancer: A Family Guide to
Diagnosis, Treatment and Survival. Cambridge, MA:
Fisher Books, 2000.
Wainrib, Barbara, et al. Men, Women, and Prostate Cancer:
A Medical and Psychological Guide for Women and the
Men they Love. Oakland, CA: New Harbinger
Publications, 2000.
PERIODICALS

Augustin, H., and P. G. Hammerer. ‘‘Disease Recurrence
After Radical Prostatectomy. Contemporary
Diagnostic and Therapeutical Strategies.’’ Minerva
Urologica e Nefrologica 55 (December 2003): 251–261.
Gomella, L. G., I. Zeltser, and R. K. Valicenti. ‘‘Use of
Neoadjuvant and Adjuvant Therapy to Prevent or
Delay Recurrence of Prostate Cancer in Patients
Undergoing Surgical Treatment for Prostate Cancer.’’
Urology 62, Supplement 1 (December 29, 2003): 46–54.
Nelson, J. B., and H. Lepor. ‘‘Prostate Cancer: Radical
Prostatectomy.’’ Urologic Clinics of North America 30
(November 2003): 703–723.
Zimmerman, R. A., and D. G. Culkin. ‘‘Clinical Strategies in
the Management of Biochemical Recurrence after
Radical Prostatectomy.’’ Clinical Prostate Cancer 2
(December 2003): 160–166.
ORGANIZATIONS

Cancer Research Institute. 681 Fifth Ave., New York, NY
10022. (800) 99CANCER. <http://
www.cancerresearch.org>.
National Prostate Cancer Coalition. 1156 15th St., NW,
Washington, DC 20005. (202) 463-9455.
<http://www.4npcc.org>.
Prostate Health Council. American Foundation for
Urologic Disease. 1128 N. Charles St., Baltimore, MD
21201-5559. (800) 828-7866. <http://www.afud.org>.

David A. Cramer, MD
Rebecca J. Frey, PhD

Prostatic acid phosphatase test see Acid
phosphatase test
3057

Prostatectomy

KEY TERMS

Prostatitis

that carries urine from the bladder to the outside of
the body (urethra). Patients feel the need to urinate
more often than usual, often urgently. Urination is
sometimes painful. It is hard to start the flow of urine
and difficult to totally empty the bladder. Patients
wake up at night to urinate. The stream may be weak
or split. Dribbling after attempts to urinate may
leave embarrassing wet spots on clothing. In severe
prostatitis blood or sand-like particles (small calcium
collections) may be passed in the urine.

Prostatitis
Definition
Prostatitis is an inflammation of the prostate
gland, a common condition in adult males. Often
caused by infection, prostatitis may develop rapidly
(acute) or slowly (chronic).

Description
Prostatitis may be the symptom-producing disease of the genitourinary tract for which men most
often seek medical help. About 40% of visits to a
specialist in genitourinary problems (urologist) are
for prostatitis. Forms of prostate inflammation
include acute and chronic bacterial prostatitis and
inflammation not caused by bacterial infection. A
painful condition called prostatodynia, which may be
caused by abnormal nerves or muscles in the region, is
also thought to be a form of prostatitis. The chronic
bacterial form is sometimes experienced by men whose
sex partners have a bacterial infection of the vagina,
making this a sexually transmitted disease. Other cases
occur when small stones form within the prostate and
become infected. Sometimes infection is caused by
poor hygiene, surgical procedures, or even swimming
in polluted water.
The sexually transmitted disease gonorrhea may
sometimes cause prostatitis, and tuberculosis may
spread to the prostate. Parasites and fungi may infect
the prostate gland. Some men whose prostatitis is not
caused by any microorganism have microscopic collections of cells called granulomas in their prostate
tissue. Whether viruses also may cause prostatitis is
debatable.

Causes and symptoms
However the inflammation may begin, it causes
blockages in the tiny glands within the prostate so that
secretions build up, and the prostate swells. In acute
cases, this swelling can occur very suddenly and cause
considerable pain. When prostatitis develops gradually, trouble with the flow of urine may be the first
symptom. Small stones may form, because the body
attempts to neutralize bacteria by coating them with
calcium. These stones may become infected themselves
and make the condition worse.
Symptoms and signs that are typically experienced by men with prostatitis include:


Difficulties in urinating. Most urinary problems are
caused when the swollen prostate blocks the tube

3058



Pain. Besides pain when urinating, caused by prostate
swelling, stimulation of nerves in the prostate gland
may cause pain in the penis, one or both testicles, the
lower stomach, the low back, and the area between the
scrotum and the anus (perineum). Some patients
experience pain during or after ejaculation, whenever
they sit down or walk, or during bowel movements.



Sex and fertility. The pain of prostatitis can make it
impossible to enjoy sex. Men with prostatitis may be
troubled by early release of sperm (premature ejaculation). Occasionally there is blood in the semen. Some
of the drugs prescribed to ease the flow of the urine
can dampen the desire to have sex. Because the normal prostate secretions make up part of the semen,
prostatitis may lower fertility by severely lowering the
number of sperm and making them less mobile.



Psychological problems. A man with prostatitis who
feels that nothing can be done and he ‘‘just has to live
with it’’ may experience serious depression. Low sexual desire certainly contributes to depression.

A person with acute prostatitis may suddenly
develop fever and chills, along with rapidly developing
urinary symptoms and pain in the perineum or low
back. This state is a medical emergency that demands
immediate medical help.

Diagnosis
Most often the symptoms and physical findings are
enough to form a diagnosis of prostatitis. When the
examiner inserts a finger in the rectum, the swollen
prostate can be felt; it may be extremely tender when
probed. Squeezing the gland slightly will produce a few
drops of fluid that may be cultured to learn whether
bacteria are present. The fluid typically contains a large
number of white blood cells, especially the cells used to
fight off infection (macrophages). Note: too much pressure on the prostate can force bacteria into the blood
and cause a serious general infection. Many patients
with chronic bacterial prostatitis also have recurring
urinary tract infections (diagnosed by examining and
culturing urine samples). These infections can be an
GALE ENCYCLOPEDIA OF MEDICINE

dehydration and increase the risk of bladder infection. Instead, it is best to drink plenty of water.


Diet. Most doctors recommend cutting out–or cutting down on–caffeine (as in coffee or tea), alcohol,
and spicy or acid foods. Constipation should be
avoided because large, hard bowel movements may
press on the swollen prostate and cause great pain.
Bran cereals and whole-grain breads are helpful.



Exercise. It is especially important for patients with
chronic prostatitis to keep up their activity level.
Simply walking often will help (unless walking happens to make the pain worse).



Frequent ejaculation. Ejaculating two or three times
a week often is recommended, especially when taking
antibiotics.

Treatment
Acute prostatitis is first treated with antibiotics.
Even though it may be difficult for drugs to actually
get into the inflamed prostate, most patients do quickly
get better. If intravenous antibiotics are needed or the
bladder is retaining urine, a hospital stay may be necessary. Broad-spectrum antibiotics that work against
most bacteria are used first. At the same time tests are
done with samples of prostatic fluid to determine which
bacterium is causing the infection, so that drugs can be
prescribed to fight the specific germ. In chronic cases,
the best results are obtained with a combination of the
antibiotics trimethoprim and sulfamethoxazole. Oral
antibiotics should be given for one to three months;
longer, if necessary. If a fungus or some other organism
is causing infection, special drugs are available. If
chronic prostatitis continues despite all medical efforts
and is seriously affecting the patient’s life, the prostate
may be removed surgically.
Nonbacterial prostatitis requires other measures
to relieve urinary symptoms. These measures include
drugs that fight inflammation (steroids or nonsteroids) and a type of drug called an alpha-blocker that
reduces muscle tension. Reduced muscle tension eases
urine flow, allowing the bladder to empty. A narrowed
urethra may be widened by placing a collapsed balloon at the site of obstruction and expanding it. This
procedure is called balloon dilation. The effects of such
dilation are usually temporary. Some physicians
believe that stress is an important factor in prostatitis,
and therefore prescribe diazepam (Valium) or another
tranquilizer. The type of prostatitis known as prostatodynia is usually treated with a combination of muscle relaxing drugs, heat, special exercises, and
sometimes a tranquilizer.
There are a number of ‘‘tips’’ for relieving symptoms of prostatitis. They are especially helpful early on,
before antibiotics have a chance to cure infection, or for
patients with chronic or non-bacterial prostatitis:


Hot sitz baths. Exposing the perineum to very hot
water for 20 minutes or longer often relieves pain.



Ice. When heat does not help, ice packs, or simply
placing a small ice cube in the rectum, may relieve
pain for hours.



Water. A patient who has to urinate very often may
want to cut back on his fluid intake but this will cause

GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
A treatment popularized in the Philippines is
called ‘‘prostate drainage.’’ At regular intervals, a finger is inserted into the rectum, to exert pressure on the
prostate at the same time that an antibiotic treatment
is given. Acupuncture and Chinese herbal medicine
also can be effective in treating prostatitis.
Nutritional supplements that support the prostate,
including zinc, omega-3 fatty acids, several amino
acids, and anti-inflammatory nutrients and herbs,
can help reduce pain and promote healing. Western
herbal medicine recommends saw palmetto ( Serenoa
repens) to support the prostate gland. Hot and cold
contrast sitz baths can help reduce inflammation.

Prognosis
Most patients with acute bacterial prostatitis are
cured if they receive proper antibiotic treatment.
Every effort should be made to get a cure at the
acute stage because chronic prostatitis can be much
more difficult to eliminate. If the acute illness is not
controlled, complications such as a localized infection
(prostatic abscess), kidney infection, or infection of the
blood (septicemia) may develop. When chronic prostatitis cannot be cured, it still is possible to keep urinary symptoms under control and keep the patient
active by using low doses of antibiotics and other
measures. If a man with any form of prostatitis develops serious psychological problems, he should be
referred to a psychiatric specialist.

Prevention
Potential sources of infection should be avoided.
Good perineal hygiene should be maintained and sex
3059

Prostatitis

important clue to the diagnosis. If doubt remains, the
urologist may insert a special instrument called a cystoscope through the penis to directly view the prostate
from inside and see whether it looks inflamed.

Protease inhibitors

Purpose

KEY TERMS
Culture—A test in which a sample of body fluid,
such as prostatic fluid, is placed on materials specially formulated to grow microorganisms. A culture is used to learn what type of bacterium is
causing infection.
Cystoscope—A viewing instrument that is passed
up the urethra into the region of the prostate to get a
good look at the organ ‘‘from the inside.’’
Ejaculation—The process by which semen (made up
in part of prostatic fluid) is ejected by the erect penis.
Granuloma—A cluster of cells that form in tissue
which has been inflamed for some time.
Perineum—An area close to the prostate, between
the scrotum and anus.

should be avoided when one’s partner has an active
bacterial vaginal infection. If the kidneys, bladder, or
other genitourinary organs are infected, prompt treatment may prevent the development of prostatitis. By
far the best way of preventing chronic prostatitis is to
treat an initial acute episode promptly and effectively.
Resources
ORGANIZATIONS

Prostate Health Council, American Foundation for
Urologic Disease. 1128 N. Charles St., Baltimore, MD
21201. (800) 242-AFUD.
Prostatitis Foundation, Information Distribution Center.
2029 Ireland Grove Park, Bloomington, IL 61704. (309)
664-6222. <http://www.prostate.org>.

David A. Cramer, MD

Prosthetic joint infection see Infectious
arthritis

Protease inhibitors
Definition
A protease inhibitor is a type of drug that cripples
the enzyme protease. An enzyme is a substance that
triggers chemical reactions in the body. The human
immunodeficiency virus (HIV) uses protease in the
final stages of its reproduction (replication) process.
3060

The drug is used to treat selected patients with
HIV infection. Blocking protease interferes with HIV
reproduction, causing it to make copies of itself that
cannot infect new cells. The drug may improve symptoms and suppress the infection but does not cure it.

Precautions
Patients should not discontinue this drug even if
symptoms improve without consulting a doctor.
These drugs do not necessarily reduce the risk of
transmitting HIV to others through sexual contact, so
patients should avoid sexual activities or use condoms.

Description
Protease inhibitors are considered one of the most
potent medications for HIV developed so far.
This class of drugs includes indinavir (Crixivan),
ritonavir (Norvir), nelfinavir (Viracept), amprenavir
(Agenerase), lopinavir plus ritonavir (Kaletra), saquinavir (Fortovase), and a new drug called atazanavir
(Reyataz). Reyataz received approval from the U.S.
Food and Drug Administration (FDA) in mid-2003
and was the first protease inhibitor approved for oncedaily dosing. Several weeks or months of drug therapy
may be required before the full benefits are apparent.
The drug should be taken at the same time each day.
Some types should be taken with a meal to help the body
absorb them. Each of the types of protease inhibitor may
have to be taken in a different way. In most cases,
protease inhibitors are part of a combination therapy,
used in conjunction with other classes of HIV drugs.

Risks
Common side effects include diarrhea, stomach
discomfort, nausea, and mouth sores. Less often,
patients may experience rash, muscle pain, headache,
or weakness. Rarely, there may be confusion, severe
skin reaction, or seizures. Some of these drugs can
have interactions with other medication, and indinavir
can be associated with kidney stones. Diabetes or high
blood pressure may become worse when these drugs
are taken. Reyatraz has been shown to have fewer side
effects than some protease inhibitors, though it can
interact with other medications, including certain
heart medications and antidepressants.
Experts do not know whether the drugs pass into
breast milk, so breastfeeding mothers should avoid
them or should stop nursing until the treatment is
completed.
GALE ENCYCLOPEDIA OF MEDICINE

Human immunodeficiency virus (HIV)—The virus
that causes AIDS.

Drugs that may cause increased protein levels
include the anabolic steroids, androgens (male hormones), growth hormone, insulin, and progesterone.
Drugs that may decrease protein levels include estrogen, drugs poisonous to the liver, and oral
contraceptives.

Resources

Description

PERIODICALS

‘‘HIV Drugs Approved as of August 2003.’’ AIDS
Treatment News July 25, 2003: 4.
LoBuono, Charlotte. ‘‘FDA Gives Bod to First Once-daily
Protease Inhibitor.’’ Drug Topics July 21, 2003: 16.
Wilson, Billie Ann. ‘‘Understanding Strategies for
Treating HIV.’’Medical Surgical Nursing 6 (April 1,
1997): 109–111.
ORGANIZATIONS

National AIDS Treatment Advocacy Project. 580
Broadway, Ste. 403, New York, NY 10012. (888)
266-2827. <http://www.natap.org>.

Carol A. Turkington
Teresa G. Odle

Protein-calorie malnutrition see Proteinenergy malnutrition

Protein components test
Definition
Protein components tests measure the amounts
and types of protein in the blood. Proteins are constituents of muscle, enzymes, hormones, transport proteins, hemoglobin, and other functional and structural
elements of the body. Albumin and globulin make up
most of the protein within the body and are measured
in the total protein of the blood and other body fluids.
Thus, the serum (blood) protein components test measures the total protein, as well as its albumin and
globulin components in the blood.

Purpose
The protein components test is used to diagnose
diseases that either affect proteins as a whole, or
that involve a single type of protein. The test is also
used to monitor the course of disease in certain cancers,
intestinal and kidney protein-wasting states, immune
disorders, liver dysfunction, and impaired nutrition.
GALE ENCYCLOPEDIA OF MEDICINE

Proteins are large molecules (complex organic
compounds) that consist of amino acids, sugars, and
lipids. There are two main types of proteins: those that
are made of fiber and form the structural basis of body
tissues, such as hair, skin, muscle, tendons, and cartilage; and globular proteins (generally water soluble),
which interact with many hormones, various other
proteins in the blood, including hemoglobin and antibodies, and all the enzymes (substances that promote
biochemical reactions in the body).
Proteins are needed in the diet to supply the body
with amino acids. Ingested proteins are broken down in
the digestive system to amino acids, which are then
absorbed and rebuilt into new body proteins. One of
the most important functions of proteins in the body is
to contribute to the osmotic pressure (the movement of
water between the bloodstream and tissues). An example of this is seen in diseases that result in damage to the
filtering units of the kidneys (nephrotic syndrome). A
severe loss of protein from the bloodstream into the
urine (proteinuria) results, lowering the protein content
of the blood and resulting in fluid retention, or edema.
Albumin and globulin are two key components of
protein. Albumin is made in the liver and constitutes
approximately 60% of the total protein. The main
function of albumin is to maintain osmotic pressure
and to help transport certain blood constituents
around the body via the bloodstream. Because albumin is made in the liver, it is one element that is used to
monitor liver function.
Globulin is the basis for antibodies, glycoproteins
(protein-carbohydrate compounds), lipoproteins (proteins involved in fat transport), and clotting factors.
Globulins are divided into three main groups, the
alpha-, beta-, and gammaglobulins. Alphaglobulins
include enzymes produced by the lungs and liver, and
haptoglobin, which binds hemoglobin together. The
betaglobulins consist mostly of low-density lipoproteins
(LDLs), substances involved in fat transport. All of the
gammaglobulins are antibodies, proteins produced by
the immune system in response to infection, during
allergic reaction, and after organ transplants.
3061

Protein components test

Precautions

KEY TERMS

Protein electrophoresis

Both serum albumin and globulin are measures of
nutrition. Malnourished patients, especially after surgery, demonstrate greatly decreased protein levels,
while burn patients and those who have protein-losing
syndromes show low levels despite normal synthesis.
Pregnancy in the third trimester is also associated with
reduced protein levels.
The relationship of albumin to globulin is determined by ratio, so when certain diseases cause the
albumin levels to drop, the globulin level will be
increased by the body in an effort to maintain a normal total protein level. For example, when the liver is
unable to synthesize sufficient albumin in chronic liver
disease, the albumin level will be low, but the globulin
levels will be normal or higher than normal. In such
cases, the protein components test is an especially
valuable diagnostic aid because it determines the
ratio of albumin to globulin, as well as the total protein level. It should be noted, however, that when
globulin is provided as a calculation (total protein –
albumin = globulin), the result is much less definitive
than other methods of determining globulin.
Consequently, when the albumin/globulin ratio
(A/G ratio) is less than 1.0, more precise tests should
be ordered. These tests include protein electrophoresis, a method of separating the different blood proteins into groups. If the protein electrophoresis
indicates a rise, or ‘‘spike’’ at the globulin level, an
even more specific test for globulins, called immunoelectrophoresis, should be ordered to separate out the
various globulins according to type. Some diseases
characterized by dysproteinemia (derangement of the
protein content of the blood), have typical electrophoretic globulin peaks.

Preparation
Unless this is requested by the physician, there is
no need that the patient restrict food or fluids before
the test.

Risks

KEY TERMS
Nephrotic syndromes—A collection of symptoms
that result from damage to the filtering units of the
kidney (glomeruli) causing severe loss of protein
from the blood into the urine.

Abnormal results
Increased total protein levels are seen in dehydration, in some cases of chronic liver disease (like autoimmune hepatitis and cirrhosis), and in certain tropical
diseases (for example, leprosy). Very low total protein
levels (less than 4.0 g/dl) and low albumin cause the
edema (water retention) usually seen in nephrotic syndromes. Decreased protein levels may be seen in pregnancy, chronic alcoholism, prolonged immobilization,
heart failure, starvation, and malabsorption or
malnutrition.
Increased albumin levels are found in dehydration.
Decreased albumin levels are indicative of liver disease,
protein-losing syndromes, malnutrition, inflammatory
disease, and familial idiopathic (of unknown cause) dysproteinemia, a genetic disease in which the albumin is
significantly reduced and globulins increased.
Increased globulin levels are found in multiple
myeloma and Waldenström’s macroglobulinemia,
two cancers characterized by overproduction of gammaglobulin from proliferating plasma cells. Increased
globulin levels are also found in chronic inflammatory
diseases such as rheumatoid arthritis, acute and
chronic infection, and cirrhosis. Decreased globulin
levels are seen in genetic immune disorders and secondary immune deficiency.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Risks posed by this test are minimal, but may
include slight bleeding from the blood-drawing site,
fainting or lightheadedness after venipuncture, or hematoma (blood accumulating under the puncture site).

Normal results
Reference values vary from laboratory to laboratory, but can generally be found within the following
ranges: Total protein: 6.4–8.3 g/dL; albumin: 3.5–5.0
g/dL; globulin: 2.3–3.4 g/dL.
3062

Protein electrophoresis
Definition
Electrophoresis is a technique used to separate different elements (fractions) of a blood sample into
GALE ENCYCLOPEDIA OF MEDICINE

by attracting water to areas with higher concentrations of salts or proteins.
GLOBULINS. Globulins are another type of protein, larger in size than albumin. They are divided
into three main groups: alpha, beta, and gamma.


Alphaglobulins. These proteins include alpha1 and
alpha2 globulins. Alpha1 globulin is predominantly
alpha1 antitrypsin, an enzyme produced by the lungs
and liver. Alpha2 globulin, which includes serum
haptoglobin, is a protein that binds hemoglobin to
prevent its excretion by the kidneys. Various other
alphaglobulins are produced as a result of inflammation, tissue damage, autoimmune disorders, or certain cancers.



Betaglobulins. These include low-density substances
involved in fat transport (lipoproteins), iron transport (transferrin), and blood clotting (plasminogen
and complement).



Gammaglobulins. All of the gammaglobulins are
antibodies–proteins produced by the immune system
in response to infection, allergic reactions, and organ
transplants. If serum protein electrophoresis has
demonstrated a significant rise at the gammaglobulin
level, immunoelectrophoresis is done to identify the
specific globulin that is involved.

Purpose
Protein electrophoresis is used to evaluate, diagnose, and monitor a variety of diseases and conditions.
It can be used for these purposes because the levels of
different blood proteins rise or fall in response to such
disorders as cancer, intestinal or kidney protein-wasting syndromes, disorders of the immune system, liver
dysfunction, impaired nutrition, and chronic fluidretaining conditions.

Precautions
Certain other diagnostic tests or prescription
medications can affect the results of SPEP tests. The
administration of a contrast dye used in some other
tests may falsely elevate protein levels. Drugs that can
alter results include aspirin, bicarbonates, chlorpromazine (Thorazine), corticosteroids, isoniazid (INH),
and neomycin (Mycifradin).

Description
Proteins are major components of muscle,
enzymes, hormones, hemoglobin, and other body tissues. Proteins are composed of elements that can be
separated from one another by several different techniques: chemical methods, ultracentrifuge, or electrophoresis. There are two major types of electrophoresis:
protein electrophoresis and immunoelectrophoresis.
Immunoelectrophoresis is used to assess the blood
levels of specific types of proteins called immunoglobulins. An immunoelectrophoresis test is usually
ordered if a SPEP test has a ‘‘spike,’’ or rise, at the
immunoglobulin level. Protein electrophoresis is used
to determine the total amount of protein in the blood,
and to establish the levels of other types of proteins
called albumin, alpha1 globulin, alpha2 globulin, and
beta-globulin.
Blood proteins
ALBUMIN. Albumin is a protein that is made in the

liver. It helps to retain elements like calcium, some
hormones, and certain drugs in the circulation by
binding to them to prevent their being filtered out by
the kidneys. Albumin also acts to regulate the movement of water between the tissues and the bloodstream
GALE ENCYCLOPEDIA OF MEDICINE

Electrophoretic measurement of proteins
All proteins have an electrical charge. The SPEP
test is designed to make use of this characteristic.
There is some difference in method, but basically the
sample is placed in or on a special medium (e.g., a gel),
and an electric current is applied to the gel. The protein particles move through the gel according to the
strength of their electrical charges, forming bands or
zones. An instrument called a densitometer measures
these bands, which can be identified and associated
with specific diseases. For example, a decrease in albumin with a rise in the alpha2 globulin usually indicates
an acute reaction of the type that occurs in infections,
burns, stress, or heart attack. On the other hand, a
slight decrease in albumin, with a slight increase in
gammaglobulin, and a normal alpha2 globulin is
more indicative of a chronic inflammatory condition,
as might be seen in cirrhosis of the liver.
Protein electrophoresis is performed on urine
samples to classify kidney disorders that cause protein
loss. Here also certain band patterns are specific for
disease. For example, the identification of a specific
protein called the Bence Jones protein (by performing
the Bence Jones protein test) during the procedure
suggests multiple myeloma.
3063

Protein electrophoresis

individual components. Serum protein electrophoresis
(SPEP) is a screening test that measures the major
blood proteins by separating them into five distinct fractions: albumin, alpha1, alpha2, beta, and gamma proteins. Protein electrophoresis can also be performed on
urine.

Protein-energy malnutrition

Preparation
The serum protein electrophoresis test requires a
blood sample. It is not necessary for the patient to
restrict food or fluids before the test. The urine protein
electrophoresis test requires either an early morning
urine sample or a 24-hour urine sample according to
the physician’s request. The doctor should check to see
if the patient is taking any medications that may affect
test results.

Risks
Risks posed by the blood test are minimal but may
include slight bleeding from the puncture site, fainting
or lightheadedness after the blood is drawn, or the
development of a small bruise at the puncture site.

KEY TERMS
Albumin—A blood protein that is made in the liver
and helps to regulate water movement in the body.
Electrophoresis—A technique for separating various blood fractions by running an electric current
through a gel containing a blood sample.
Globulins—A group of proteins in blood plasma
whose levels can be measured by electrophoresis
in order to diagnose or monitor a variety of serious
illnesses.
Haptoglobin—A protein in blood plasma that binds
hemoglobin.
Immunoglobulins—Any of several types of globulin proteins that function as antibodies.

Normal results
The following values are representative, although
there is some variation among laboratories and specific methods. These values are based on the agarose
system.


total protein: 5.9–8.0 g/dL



albumin: 4.0–5.5 g/dL



alpha1 globulin: 0.15–0.25 g/dL



alpha2 globulin: 0.43–0.75 g/dL



beta-globulin: 0.5–1.0 g/dL



gammaglobulin: 0.6–1.3 g/dL

arthritis, systemic lupus erythematosus); cirrhosis;
acute and chronic infection; and a cancerous disease
characterized by uncontrolled multiplication of plasma
cells in the bone marrow (multiple myeloma).
Gammaglobulins are decreased in a variety of genetic
immune disorders, and in secondary immune deficiency
related to steroid use, leukemia, or severe infection.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnosticand
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Abnormal results
Albumin levels are increased in dehydration. They
are decreased in malnutrition, pregnancy, liver disease,
inflammatory diseases, and such protein-losing syndromes as malabsorption syndrome and certain kidney
disorders.
Alpha1 globulins are increased in inflammatory
diseases. They are decreased or absent in juvenile pulmonary emphysema, which is a genetic disease.
Alpha2 globulins are increased in a kidney disorder called nephrotic syndrome. They are decreased in
patients with an overactive thyroid gland (hyperthyroidism) or severe liver dysfunction.
Betaglobulin levels are increased in conditions
of high cholesterol levels (hypercholesterolemia) and
iron deficiency anemia. They are decreased in
malnutrition.
Gammaglobulin levels are increased in chronic
inflammatory disease (for example, rheumatoid
3064

Protein-energy malnutrition
Definition
Protein-energy malnutrition (PEM) is a potentially fatal body-depletion disorder. It is the leading
cause of death in children in developing countries.

Description
PEM is also referred to as protein-calorie malnutrition. It develops in children and adults whose consumption of protein and energy (measured by calories)
is insufficient to satisfy the body’s nutritional needs.
While pure protein deficiency can occur when a person’s diet provides enough energy but lacks the protein
GALE ENCYCLOPEDIA OF MEDICINE

Although PEM is not prevalent among the general population of the United States, it is often seen in
elderly people who live in nursing homes and in children whose parents are poor. PEM occurs in one of
every two surgical patients and in 48% of all other
hospital patients.
Types of PEM
Primary PEM results from a diet that lacks sufficient sources of protein and/or energy. Secondary PEM
is more common in the United States, where it usually
occurs as a complication of AIDS, cancer, chronic kidney failure, inflammatory bowel disease, and other
illnesses that impair the body’s ability to absorb or use
nutrients or to compensate for nutrient losses. PEM can
develop gradually in a patient who has a chronic illness
or experiences chronic semi-starvation. It may appear
suddenly in a patient who has an acute illness.
Kwashiorkor
Kwashiorkor, also called wet protein-energy malnutrition, is a form of PEM characterized primarily by
protein deficiency. This condition usually appears at
the age of about 12 months when breastfeeding is
discontinued, but it can develop at any time during a
child’s formative years. It causes fluid retention
(edema); dry, peeling skin; and hair discoloration.
Marasmus
Primarily caused by energy deficiency, marasmus is
characterized by stunted growth and wasting of muscle
and tissue. Marasmus usually develops between the
ages of six months and one year in children who have
been weaned from breast milk or who suffer from
weakening conditions like chronic diarrhea.

Causes and symptoms
Secondary PEM symptoms range from mild to
severe, and can alter the form or function of almost
every organ in the body. The type and intensity of
symptoms depend on the patient’s prior nutritional
status and on the nature of the underlying disease
and the speed at which it is progressing.
Mild, moderate, and severe classifications have
not been precisely defined, but patients who lose 10–
20% of their body weight without trying are usually
said to have moderate PEM. This condition is also
GALE ENCYCLOPEDIA OF MEDICINE

characterized by a weakened grip and inability to perform high-energy tasks.
Losing 20% of body weight or more is generally
classified as severe PEM. People with this condition
can’t eat normal-sized meals. They have slow heart
rates and low blood pressure and body temperatures.
Other symptoms of severe secondary PEM include
baggy, wrinkled skin; constipation; dry, thin, brittle
hair; lethargy; pressure sores and other skin lesions.
Kwashiorkor
People who have kwashiorkor often have extremely thin arms and legs, but liver enlargement and
ascites (abnormal accumulation of fluid) can distend
the abdomen and disguise weight loss. Hair may turn
red or yellow. Anemia, diarrhea, and fluid and electrolyte disorders are common. The body’s immune system
is often weakened, behavioral development is slow,
and mental retardation may occur. Children may
grow to normal height but are abnormally thin.
Kwashiorkor-like secondary PEM usually develops in patients who have been severely burned, suffered trauma, or had sepsis (tissue-destroying
infection) or another life-threatening illness. The condition’s onset is so sudden that body fat and muscle
mass of normal-weight people may not change. Some
obese patients even gain weight.
Marasmus
Profound weakness accompanies severe marasmus. Since the body breaks down its own tissue to use
as calories, people with this condition lose all their body
fat and muscle strength, and acquire a skeletal appearance most noticeable in the hands and in the temporal
muscle in front of and above each ear. Children with
marasmus are small for their age. Since their immune
systems are weakened, they suffer from frequent infections. Other symptoms include loss of appetite, diarrhea, skin that is dry and baggy, sparse hair that is dull
brown or reddish yellow, mental retardation, behavioral retardation, low body temperature (hypothermia), and slow pulse and breathing rates.
The absence of edema distinguishes marasmuslike secondary PEM, a gradual wasting process that
begins with weight loss and progresses to mild, moderate, or severe malnutrition (cachexia). It is usually
associated with cancer, chronic obstructive pulmonary disease (COPD), or another chronic disease that is
inactive or progressing very slowly.
Some individuals have both kwashiorkor and
marasmus at the same time. This most often occurs
3065

Protein-energy malnutrition

minimum, in most cases the deficiency will be dual.
PEM may also occur in persons who are unable to
absorb vital nutrients or convert them to energy essential for healthy tissue formation and organ function.

Protein-energy malnutrition

when a person who has a chronic, inactive condition
develops symptoms of an acute illness.
Hospitalized patients
Difficulty chewing, swallowing, and digesting
food, pain, nausea, and lack of appetite are among
the most common reasons that many hospital patients
don’t consume enough nutrients. Nutrient loss can be
accelerated by bleeding, diarrhea, abnormally high
sugar levels (glycosuria), kidney disease, malabsorption disorders, and other factors. Fever, infection, surgery, and benign or malignant tumors increase the
amount of nutrients hospitalized patients need. So
do trauma, burns, and some medications.

Diagnosis
A thorough physical examination and a health
history that probes eating habits and weight changes,
focuses on body-fat composition and muscle strength,
and assesses gastrointestinal symptoms, underlying
illness, and nutritional status is often as accurate as
blood tests and urinalyses used to detect and document abnormalities.
Some doctors further quantify a patient’s nutritional status by:


comparing height and weight to standardized norms



calculating body mass index (BMI)



measuring skinfold thickness or the circumference of
the upper arm

Treatment
Treatment is designed to provide adequate nutrition, restore normal body composition, and cure the
condition that caused the deficiency. Tube feeding or
intravenous feeding is used to supply nutrients to
patients who can’t or won’t eat protein-rich foods.
In patients with severe PEM, the first stage of
treatment consists of correcting fluid and electrolyte
imbalances, treating infection with antibiotics that
don’t affect protein synthesis, and addressing related
medical problems. The second phase involves replenishing essential nutrients slowly to prevent taxing the
patient’s weakened system with more food than it can
handle. Physical therapy may be beneficial to patients
whose muscles have deteriorated significantly.

Prognosis
Most people can lose up to 10% of their body
weight without side effects, but losing more than
3066

40% is almost always fatal. Death usually results
from heart failure, an electrolyte imbalance, or low
body temperature. Patients with certain symptoms,
including semiconsciousness, persistent diarrhea,
jaundice, and low blood sodium levels, have a poorer
prognosis than other patients. Recovery from marasmus usually takes longer than recovery from kwashiorkor. The long-term effects of childhood
malnutrition are uncertain. Some children recover
completely, while others may have a variety of lifelong
impairments, including an inability to properly absorb
nutrients in the intestines and mental retardation. The
outcome appears to be related to the length and severity of the malnutrition, as well as to the age of the child
when the malnutrition occurred.

Prevention
Breastfeeding a baby for at least six months is
considered the best way to prevent early-childhood
malnutrition. Preventing malnutrition in developing
countries is a complicated and challenging problem.
Providing food directly during famine can help in the
short-term, but more long-term solutions are needed,
including agricultural development, public health programs (especially programs that monitor growth and
development, as well as programs that provide nutritional information and supplements), and improved
food distribution systems. Programs that distribute
infant formula and discourage breastfeeding should
be discontinued, except in areas where many mothers
are infected with HIV.
Every patient being admitted to a hospital should
be screened for the presence of illnesses and conditions
that could lead to PEM. The nutritional status of
patients at higher-than-average risk should be more
thoroughly assessed and periodically reevaluated
during extended hospital stays or nursing home
residence.
Resources
ORGANIZATIONS

American College of Nutrition. 722 Robert E. Lee Drive,
Wilmington, NC 20412-0927. (919) 152-1222.
American Institute of Nutrition. 9650 Rockville Pike,
Bethesda, MD 20814-3990. (301) 530-7050.
Food and Nutrition Information Center. 10301 Baltimore
Boulevard, Room 304, Beltsville, MD 20705-2351.
<http://www.nalusda.gov/fnic>.

Maureen Haggerty

Protein-modified diet see Diets
GALE ENCYCLOPEDIA OF MEDICINE

Definition
The prothrombin time test belongs to a group
of blood tests that assess the clotting ability of
blood. The test is also known as the pro time or
PT test.

Purpose
The PT test is used to monitor patients taking
certain medications as well as to help diagnose clotting
disorders.

Preparation
The doctor should check to see if the patient is
taking any medications that may affect test results.
This precaution is particularly important if the patient
is taking warfarin, because there are a number of
medications that can interact with warfarin to increase
or decrease the PT time.

Aftercare
Diagnosis
Patients who have problems with delayed blood
clotting are given a number of tests to determine the
cause of the problem. The prothrombin test specifically evaluates the presence of factors VIIa, V, and X,
prothrombin, and fibrinogen. Prothrombin is a
protein in the liquid part of blood (plasma) that is
converted to thrombin as part of the clotting process.
Fibrinogen is a type of blood protein called a globulin;
it is converted to fibrin during the clotting process. A
drop in the concentration of any of these factors will
cause the blood to take longer to clot. The PT test is
used in combination with the partial thromboplastin
time (PTT) test to screen for hemophilia and other
hereditary clotting disorders.
Monitoring
The PT test is also used to monitor the condition of patients who are taking warfarin
(Coumadin). Warfarin is a drug that is given to
prevent clots in the deep veins of the legs and to
treat pulmonary embolism. It interferes with blood
clotting by lowering the liver’s production of certain clotting factors.

Description
A sample of the patient’s blood is obtained by
venipuncture. The blood is collected in a tube that
contains sodium citrate to prevent the clotting process from starting before the test. The blood cells
are separated from the liquid part of blood
(plasma). The PT test is performed by adding the
patient’s plasma to a protein in the blood (thromboplastin) that converts prothrombin to thrombin.
The mixture is then kept in a warm water bath at
378C for one to two minutes. Calcium chloride is
added to the mixture in order to counteract the
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare consists of routine care of the area
around the puncture mark. Pressure is applied for a
few seconds and the wound is covered with a
bandage.

Risks
The primary risk is mild dizziness and the possibility of a bruise or swelling in the area where the blood
was drawn. The patient can apply moist warm
compresses.

Normal results
The normal prothrombin time is 11–15 seconds,
although there is some variation depending on the
source of the thromboplastin used in the test. (For
this reason, laboratories report a normal control
value along with patient results.) A prothrombin
time within this range indicates that the patient has
normal amounts of clotting factors VII and X.

Abnormal results
A prolonged PT time is considered abnormal.
The prothrombin time will be prolonged if the concentration of any of the tested factors is 10% or more
below normal plasma values. A prolonged prothrombin time indicates a deficiency in any of factors VII,
X, V, prothrombin, or fibrinogen. It may mean that
the patient has a vitamin K deficiency, a liver disease,
or disseminated intravascular coagulation (DIC).
The prothrombin time of patients receiving warfarin
therapy will also be prolonged—usually in the range
of one and one half to two times the normal PT time.
A PT time that exceeds approximately two and a half
times the control value (usually 30 seconds or longer)
is grounds for concern, as abnormal bleeding may
occur.
3067

Prothrombin time

Prothrombin time

sodium citrate and allow clotting to proceed. The
test is timed from the addition of the calcium
chloride until the plasma clots. This time is called
the prothrombin time.

Proton pump inhibitors

Injury to lining of
vessels exposes collagen
fibers; platelets adhere.

Platelet plug forms.

Fibrin clot with
trapped cells.

Platelets

Collagen
fibers
Platelet releases chemicals
that make nearby platelets "sticky."
Clotting factors from:

Damaged cells

Calcium and
other factors
in blood plasma

Prothrombin

Thrombin

Platelets

Fibrinogen

Fibrin

The blood clotting process. (Illustration by Hans & Cassady.)

KEY TERMS
Disseminated intravascular coagulation (DIC)—A
condition in which spontaneous bleeding and clot
formation occur throughout the circulatory system.
DIC can be caused by transfusion reactions and a
number of serious illnesses.
Fibrin—The protein formed as the end product of
the blood clotting process when fibrinogen interacts
with thrombin.
Fibrinogen—A type of blood protein called a globulin that interacts with thrombin to form fibrin.
Plasma—The liquid part of blood, as distinct from
blood cells.
Prothrombin—A protein in blood plasma that is
converted to thrombin during the clotting process.
Thrombin—An enzyme in blood plasma that helps
to convert fibrinogen to fibrin during the last stage of
the clotting process.
Thromboplastin—A protein in blood that converts
prothrombin to thrombin.
Warfarin—A drug given to control the formation of
blood clots. The PT test can be used to monitor
patients being treated with warfarin.
3068

Resources
BOOKS

Berktow, Robert, et al., editors. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

John T. Lohr, PhD

Proton pump inhibitors
Definition
The proton pump inhibitors are a group of drugs
that reduce the secretion of gastric (stomach) acid.
They act by binding with the enzyme H+, K(+)ATPase, hydrogen/potassium adenosine triphosphatase, which is sometimes referred to as the proton
pump. This enzyme causes parietal cells of the stomach lining to produce acid.
Although they perform much the same functions
as the histamine H-2 receptor blockers, the proton
pump inhibitors reduce stomach acid more and over
a longer period.
GALE ENCYCLOPEDIA OF MEDICINE

Proton pump inhibitors are used to treat ulcers;
gastroesophageal reflux disease (GERD), a condition
in which backward flow of acid from the stomach
causes heartburn and injury of the food pipe (esophagus); and conditions in which the stomach produces
too much acid, such as Zollinger-Ellison syndrome.
Omeprazole is used in combination with other medications to treat recurrent ulcers caused by helicobacter
pylori infections.
Two of the proton pump inhibitors, lansoprazole
and omeprazole, have been used to improve pancreatic enzyme absorption in cystic fibrosis patients with
intestinal malabsorption.
Proton pump inhibitors may be used to protect
against the ulcerogenic effects of non-steroidal antiinflammatory drugs and to help heal ulcers caused by
these drugs.

Description
There are five drugs in this class: esomeprazole
(Nexium), lansoprazole (Prevacid), omeprazole
(Prilosec), pantoprazole (Protonix), and rabeprazole
(Aciphex). They act in a similar manner, and their
cautions and adverse effects are similar.
The products are generally formulated as entericcoated granules. Absorption does not start until the
granules have left the stomach and reached the intestine, so the onset of action is delayed about an hour,
subject to gastric emptying time. Since they act slowly,
proton pump inhibitors are not a suitable alternative
to antacids which have a rapid effect.
Although these drugs are eliminated from the
body relatively quickly, usually within 90 minutes
of absorption, they all work for over 24 hours after
a dose. This is because the factor that determines
duration of action is how long it takes the body to
replace the H+, K(+)-ATPase. There is some
build up over time. For example, a single dose of
lansoprazole reduces stomach acid by 71%, but
after a week of regular dosing, the acid reduction
rises to 80%.
For treatment of recurrent ulcers, the proton
pump inhibitors are part of combination therapy
that uses an antibiotic (occasionally two antibiotics)
and proton pump inhibitor. There are a number of
regimens, and while they may vary in the selection of
specific drugs, or even types of drugs used, usually
they include a proton pump inhibitor. The cure rates
are all within similar ranges for these regimens.
GALE ENCYCLOPEDIA OF MEDICINE

Recommended dosage
Dose varies with the indication. The following are
commonly prescribed doses:


Esomeprazole: 20 to 40 mg once a day.



Lansoprazole: 15 to 30 mg once a day.



Omeprazole: 20 to 40 mg once a day.



Pantoprazole: 40 mg once or twice a day.



Rabeprazole: 20 mg once a day. In hypersecretory
conditions, doses as high as 60 mg twice daily have
been reported.

In the above examples, the lower dose is usually
adequate for GERD, while the higher dose may be
required for ulcer therapy or hypersecretory
conditions.

Precautions
Proton pump inhibitors should not be given to
any patient who has shown a reaction to any of the
components of the drug or a related drug. Proton
pump inhibitors should also not be given to patients
with severe liver disease.
Omeprazole is pregnancy category C, while
esomeprazole, lansoprazole, rabeprazole, and pantoprazole are category B. As of 2005, there are no adequate and well-controlled studies concerning the
effects of these drugs on pregnant women. These
drugs should be used during pregnancy only if the
potential benefit justifies the risk to the fetus.
Because the proton pump inhibitors are excreted into
breast milk, they should not be used by women who
are breastfeeding their babies.
The proton pump inhibitors may mask the symptoms of stomach cancer.

Side effects
The proton pump inhibitors are relatively safe
drugs. The most commonly observed adverse effects
are constipation, diarrhea, dizziness, headache, skin
itch, and skin rash. Less often, the following adverse
effects have been reported: abdominal pain with
cramps, appetite changes, and nausea.
The following adverse effects are extremely rare
but have been reported with this class of drugs:


acute pancreatitis



anxiety



cough



depression
3069

Proton pump inhibitors

Purpose

Proton pump inhibitors

KEY TERMS
Antacid—A substance that counteracts or neutralizes acidity, usually of the stomach. Antacids have
a rapid onset of action compared to histamine H-2
receptor blockers and proton pump inhibitors, but
they have a short duration of action and require
frequent dosing.
Cystic fibrosis—A hereditary disease that appears
in early childhood, involves functional disorder of
digestive glands, and is marked especially by faulty
digestion due to a deficiency of pancreatic
enzymes, by difficulty in breathing due to mucus
accumulation in airways, and by excessive loss of
salt in the sweat.
Enteric coat—A coating put on some tablets or
capsules to prevent their disintegration in the stomach. The contents of coated tablets or capsules
will be released only when the dose reaches the
intestine. This may be done to protect the drug from
stomach acid, to protect the stomach from drug
irritation, or to delay the onset of action of the drug.
GERD—A chronic condition in which the lower
esophageal sphincter allows gastric acids to reflux
into the esophagus, causing heartburn, acid indigestion, and possible injury to the esophageal
lining.
Malabsorption—Defective or inadequate absorption of nutrients from the intestinal tract.
Parietal cells—Cells of the gastric glands that secret
hydrochloric acid.
Recurrent ulcer—Stomach ulcers that return after
apparently complete healing. These ulcers appear
to be caused by helicobacter pylori infections and
can generally be successfully treated with a combination of antibiotics and gastric acid reducing compounds, particularly the proton pump inhibitors.



upper respiratory hypersensitivity reaction



upper respiratory infection



vomiting

Interactions
Proton pump inhibitors should not be used in
conjunctions with the anti-retroviral (anti-AIDS)
drug atazanavir (Rayataz). The conjunction may
reduce the effectiveness of the atazanavir. Proton
pump inhibitors should not be used in combination
with the anti-fungal drugs itraconazole or ketoconazole. This combination may reduce the effectiveness of
the anti-fungal drugs.
Resources
BOOKS

Green, Steven M. Tarascon Pocket Pharmacopoeia. Deluxe
labcoat pocket edition. Lompoc, CA: Tarascon
Publishing, 2005.
Physicians’ Desk Reference 2005. Montvale, NJ: Thomson
Healthcare, 2004.
Yamada, Tadataka, et al., eds. Textbook of
Gastroenterology. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins, 2003.
PERIODICALS

Peura, D. A. ‘‘Prevention of nonsteroidal anti-inflammatory
drug-associated gastrointestinal symptoms and ulcer
complications.’’ American Journal of Medicine 117,
Suppl. 5A (September 6, 2004): 63S–71S.
Vanderhoff, Bruce T., and Rundsarah M. Tahboub.
‘‘Proton Pump Inhibitors: An Update.’’ American
Family Physician 66 (2002): 273–80.
Van Pinxteren, B., et al. ‘‘Short-term treatment of gastroesophageal reflux disease.’’ Journal of General Internal
Medicine 18, no. 9 (September 2003): 755–63.
Zed, P. J., et al. ‘‘Meta-analysis of proton pump inhibitors in
treatment of bleeding peptic ulcers.’’ Annals of
Pharmacotherapy 35, no. 12 (December 2001): 1528–34.
ORGANIZATION

International Foundation for Functional Gastrointestinal
Disorders. PO Box 170864, Milwaukee, WI 53217-8076.
(414)964-1799. <www.iffgd.org>.



drug toxin-related hepatitis



erythema multiforme



flu-like symptoms



myalgia



Stevens-Johnson syndrome



thrombocytopenia

PSA test see Prostate-specific antigen test



toxic epidermal necrolysis

PSDD see Premenstrual disphoric disorder



ulcerative colitis

Pseudoephedrin see Decongestants

3070

Samuel D. Uretsky, Pharm.D.

Pruritis see Itching

GALE ENCYCLOPEDIA OF MEDICINE

Definition
Pseudogout is a form of arthritis that causes pain,
redness, and inflammation in one or more joints.

Description
Pseudogout is also known by another name: calcium pyrophosphate dihydrate deposition disease
(CPPD), the basis of which is derived from the calcium
deposits that collect in the joint. The deposits or crystals, as they are sometimes called, cause pain and
inflammation in the joint. According to the Arthritis
Foundation, this can eventually weaken the cartilage,
which serves as padding between the bones, ‘‘allowing
bone to rub against bone.’’ Pseudogout typically
affects the large joints, such as the knees, wrists, and
ankles. In general, it occurs with equal frequency in
men and women.
Most often seen in older adults, pseudogout
can also affect younger patients, especially those
with diseases that put them at a greater risk of developing it, such as hemochromatosis, hypercalcemia,
hypothyroidism, ochronosis, or Wilson’s disease. Some
people, according to an article for the American
College of Rheumatology, experience attacks of
pseudogout ‘‘following joint surgery or other surgery. Because many older people have calcium crystal
deposits in their joints, any kind of insult to the joint
can trigger the release of the calcium crystals, which
then induce a painful inflammatory response.’’
Pseudogout affects about 3% of elderly people. Not
all will experience severe attacks. By their nineties,
50% of people will have joint deposits. Although
researchers have noticed that some people with
pseudogout also have a family history of the disease,
it is not clear what role genetics might play in its
development.

Causes and symptoms
As the Arthritis Foundation points out, it is
unclear what causes the crystals to form, but some
speculation exists that ‘‘an abnormality in the cartilage cells or connective tissue could be responsible’’ for their development. Acute pain and fluid
accumulation that leads to joint swelling are typical
symptoms of pseudogout. When the crystals move
into a joint, the Arthritis Foundation categorizes
the pain as ‘‘sudden and severe.’’ Many patients
report that joint motion is limited. Statistically
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Pseudogout and gout have similar symptoms,
which can be confusing. However, uric acid is associated with gout, whereas calcium pyrophosphate
crystals are associated with pseudogout. After a
patient’s detailed medical history is obtained, a diagnosis can be made based on the symptoms and medical
tests.
Using a needle, the physician can take a sample of
the synovial fluid from the swollen or painful joint to
ascertain the presence of calcium pyrophosphate crystals. The fluid will also contain white blood cells,
which can be counted to assist in the diagnosis.
Synovial fluid is the lubricating fluid that’s secreted
by the membranes that line the joints.
X rays may also be taken to confirm the presence of crystals. The x-rays may also show joint
damage or that crystals have led to a condition
called chondrocalcinosis, which is calcification of
the cartilage. Other possible causes such as gout,
rheumatoid arthritis, or infection must be ruled out
too. Blood tests can also help to confirm the diagnosis. Indeed, as the experts at MedlinePlus indicated, ‘‘careful workup, with analysis of crystals
found in the joints, should ultimately lead to the
correct diagnosis.’’

Treatment
There are a variety of treatment options. It if the
patients have an adequate support system, such as
family and friends willing to help, it makes it easier
for patients to recover faster. Patients are often
advised to avoid putting pressure on the affected
joint. In some cases, it is appropriate for the patient
to engage in special isometric exercises designed to
help their specific condition heal faster. Once the
inflammation and pain subsides, exercises are sometimes suggested to regain range of motion.
Medications can be prescribed to ease the pain, which
typically fall into the nonsteroidal anti-inflammatory
3071

Pseudogout

Pseudogout

speaking, in 50% of the cases, the patient will run
a fever. Half of all the acute pseudogout attacks will
involve a knee. The experts at MedlinePlus identify
‘‘chronic (long term) arthritis’’ as a symptom that
can be present at the time of an acute pseudogout
attack. The word ‘‘acute’’ implies short term; therefore, acute attacks of pseudogout will come and
go, but chronic arthritis may remain. In addition,
progressive degenerative arthritis is sometimes seen
in numerous joints.

Pseudogout

KEY TERMS
hemochromatosis—This disease refers to when a
person’s body absorbs too much iron.
hypercalcemia—This disease refers to when a person’s bones absorb too much calcium.
hypothyroidism—This disease refers to when a person’s thyroid gland is underactive.
ochronosis—People with this rare hereditary condition tend to develop arthritis in adulthood.
Wilson’s disease—Wilson’s disease causes the
body to retain copper, which ultimately can lead
to liver damage.

category. For example, ibuprofen (Motrin) and
naproxen (Aleve) are nonsteroidal anti-inflammatory
drugs (NSAIDs) that are used quite often, because
they are generally well tolerated and highly effective.
However, in the article Dr. Schumacher wrote for the
American College of Rheumatology he cautions
patients by stating that, ‘‘people with poor kidney
function, a history of stomach ulcers, and those who
are on blood thinners often cannot take NSAIDs.’’
Indomethacin (Indocin) is also a first-line drug that is
commonly used to treat pseudogout that falls into this
category.
When no infection is present, steroids, such as
prednisone, may be prescribed. Much of the literature discussing treatment options also suggests a
medication called colchicine, which is only available
as a generic. It is generally prescribed in low doses
and should not be used by anyone with significant
bone marrow dysfunction or renal insufficiency.
Patients should talk with their physicians regarding
any other reasons why colchicine may not be suitable
for them.
In order to relieve some of the pressure, the excess
fluid around the joint can be removed (or aspirated, as
it is sometimes called) with a needle.
Treatment options to reduce inflammation are
valuable, ‘‘because they may slow the progression of
joint degeneration that often accompanies pseudogout,’’ according to Dr. Schumacher in his American
College of Rheumatology article. If joint degeneration does occur, surgery is available to replace or
repair damaged joints; however, it is better for
patients to engage in preventative measures that

3072

will help them avoid the need for surgery. As the
old saying goes, ‘‘an ounce of prevention is worth a
pound of cure.’’

Prognosis
With regard to an acute attack of pseudogout, the
prognosis is usually very good. The symptoms usually
go away within two weeks. However, over time, joint
degeneration can occur.

Prevention
There are not specific techniques applicable to
every patient to prevent the formulation of the crystals; however, some patients with certain diseases are
at greater risk of developing them. Diagnoses and
treatment of underlying disorders is one of the most
important aspects of managing crystal-induced arthopathies. Once a causative crystal is identified and a
diagnosis has been established, long-term management and prevention can be devised.
Resources
PERIODICALS

Schumacher, H. R. ‘‘Crystal-induced arthritis: an overview.’’ American Journal of Medicine 100 (1996):
46S–52S.
OTHER

Arthritis Foundation ‘‘Calcuim pyrophosphate dehydrate
crystal deposition disease (CPPD) pseudogout.’’
Arthritis Foundation 2004. The Arthritis Foundation.
29 Mar. 2005 <http://www.arthritis.org/
DiseaseCenter/cppd.asp>.
Medline Plus ‘‘Pseudogout.’’ U.S. National Library of
Medicine July 2004. U.S. National Library of Medicine
and the National Institutes of Health. 29 Mar. 2005
<http://www.nlm.nih.gov/medlineplus/ency/
article000421.htm>.
Schumacher, H. R. ‘‘Pseudogout.’’ American College
of Rheumatology April 2004. American College
of Rheumatology. 29 Mar. 2005 <http://www.
rheumatology.org/public/factsheets/
pseudogout_new.asp>.

Lee Ann Paradise

Pseudohermaphroditism see Intersex states
Pseudomembraneous enterocolitis see
Antibiotic-associated colitis
Pseudomonas aeruginosa infection see
Pseudomonas infections

GALE ENCYCLOPEDIA OF MEDICINE

Heart and blood. P. aeruginosa is the fourth most
common cause of bacterial infections of the blood
(bacteremia). Bacteremia is common in patients with
blood cancer and patients who have pseudomonas
infections elsewhere in the body. P. aeruginosa
infects the heart valves of intravenous drug abusers
and persons with artificial heart valves.



Bones and joints. Pseudomonas infections in these
parts of the body can result from injury, the spread of
infection from other body tissues, or bacteremia.
Persons at risk for pseudomonas infections of the
bones and joints include diabetics, intravenous drug
abusers, and bone surgery patients.



Central nervous system. P. aeruginosa can cause
inflammation of the tissues covering the brain and
spinal cord (meningitis) and brain abscesses. These
infections may result from brain injury or surgery,
the spread of infection from other parts of the body,
or bacteremia.



Eye and ear. P. aeruginosa can cause infections in the
external ear canal–so-called ‘‘swimmer’s ear’’– that
usually disappear without treatment. The bacterium
can cause a more serious ear infection in elderly
patients, possibly leading to hearing problems, facial
paralysis, or even death. Pseudomonas infections of
the eye usually follow an injury. They can cause
ulcers of the cornea that may cause rapid tissue
destruction and eventual blindness. The risk factors
for pseudomonas eye infections include: wearing soft
extended-wear contact lenses; using topical corticosteroid eye medications; being in a coma; having
extensive burns; undergoing treatment in an ICU;
and having a tracheostomy or endotracheal tube.



Urinary tract. Urinary tract infections can be caused
by catheterization, medical instruments, and surgery.



Lung. Risk factors for P. aeruginosa pneumonia
include: cystic fibrosis; chronic lung disease; immunocompromised condition; being on antibiotic therapy or a respirator; and congestive heart failure.
Patients with cystic fibrosis often develop pseudomonas infections as children and suffer recurrent attacks
of pneumonia.



Skin and soft tissue. Even healthy persons can
develop a pseudomonas skin rash following exposure
to the bacterium in contaminated hot tubs, water
parks, whirlpools, or spas. This skin disorder is
called pseudomonas or ‘‘hot tub’’ folliculitis, and is
often confused with chickenpox. Severe skin infection may occur in patients with P. aeruginosa bacteremia. The bacterium is the second most common
cause of burn wound infections in hospitalized
patients.

Pseudomonas infections
Definition
A pseudomonas infection is caused by a bacterium, Pseudomonas aeruginosa, and may affect any part
of the body. In most cases, however, pseudomonas
infections strike only persons who are very ill, usually
hospitalized.

Description
P. aeruginosa is a rod-shaped organism that can
be found in soil, water, plants, and animals. Because it
rarely causes disease in healthy persons, but infects
those who are already sick or who have weakened
immune systems, it is called an opportunistic pathogen. Opportunistic pathogens are organisms that do
not ordinarily cause disease, but multiply freely in
persons whose immune systems are weakened by illness or medication. Such persons are said to be immunocompromised. Patients with AIDS have an
increased risk of developing serious pseudomonas
infections. Hospitalized patients are another highrisk group, because P. aeruginosa is often found in
hospitals. Infections that can be acquired in the hospital are sometimes called nosocomial diseases.
Of the two million nosocomial infections each
year, 10% are caused by P. aeruginosa. The bacterium is the second most common cause of nosocomial
pneumonia and the most common cause of intensive
care unit (ICU) pneumonia. Pseudomonas infections
can be spread within hospitals by health care workers, medical equipment, sinks, disinfectant solutions,
and food. These infections are a very serious problem
in hospitals for two reasons. First, patients who are
critically ill can die from a pseudomonas infection.
Second, many Pseudomonas bacteria are resistant to
certain antibiotics, which makes them difficult to
treat.
P. aeruginosa is able to infect many different parts
of the body. Several factors make it a strong opponent.
These factors include:


the ability to stick to cells



minimal food requirements



resistance to many antibiotics



production of proteins that damage tissue



a protective outer coat

Infections that can occur in specific body sites
include:
GALE ENCYCLOPEDIA OF MEDICINE

3073

Pseudomonas infections



Pseudomonas infections

Causes and symptoms
P. aeruginosa can be sudden and severe, or slow in
onset and cause little pain. Risk factors for acquiring a
pseudomonas infection include: having a serious illness; being hospitalized; undergoing an invasive procedure such as surgery; having a weakened immune
system; and being treated with antibiotics that kill
many different kinds of bacteria (broad-spectrum
antibiotics).
Each of the infections listed above has its own set
of symptoms. Pseudomonas bacteremia resembles
other bacteremias, producing fever, tiredness, muscle
pains, joint pains, and chills. Bone infections are
marked by swelling, redness, and pain at the infected
site and possibly fever. Pseudomonas meningitis causes
fever, headache, irritability, and clouded consciousness. Ear infection is associated with pain, ear drainage, facial paralysis, and reduced hearing.
Pseudomonas infections of the eye cause ulcers that
may spread to cover the entire eye, pain, reduced
vision, swelling of the eyelids, and pus accumulation
within the eye.
P. aeruginosa pneumonia is marked by chills,
fever, productive cough, difficult breathing, and bluetinted skin. Patients with cystic fibrosis with pseudomonas lung infections experience coughing, decreased
appetite, weight loss, tiredness, wheezing, rapid
breathing, fever, blue-tinted skin, and abdominal
enlargement. Skin infections can cause a range of
symptoms from a mild rash to large bleeding ulcers.
Symptoms of pseudomonas folliculitis include a red
itchy rash, headache, dizziness, earache, sore eyes,
nose, and throat, breast tenderness, and stomach
pain. Pseudomonas wound infections may secrete a
blue-green colored fluid and have a fruity smell.
Burn wound infections usually occur one to two
weeks after the burn and cause discoloration of the
burn scab, destruction of the tissue below the scab,
early scab loss, bleeding, swelling, and a blue-green
drainage.

Diagnosis
Diagnosis and treatment of pseudomonas infections can be performed by specialists in infectious
disease. Because P. aeruginosa is commonly found in
hospitals, many patients carry the bacterium without
having a full-blown infection. Consequently, the mere
presence of P. aeruginosa in patients does not constitute a diagnostic finding. Cultures, however, can be
easily done for test purposes. The organism grows
readily in laboratory media; results are usually available in two to three days. Depending on the location of
3074

the infection, body fluids that can be tested for
P. aeruginosa include blood, urine, cerebrospinal
fluid, sputum, pus, and drainage from an infected ear
or eye. X rays and other imaging techniques can be
used to assess infections in deep organ tissues.

Treatment
Medications
Because P. aeruginosa is commonly resistant to
antibiotics, infections are usually treated with two
antibiotics at once. Pseudomonas infections may be
treated with combinations of ceftazidime (Ceftaz,
Fortraz, Tazicef), ciprofloxacin (Cipro), imipenem
(Primaxin), gentamicin (Garamycin), tobramycin
(Nebcin), ticarcillin-clavulanate (Timentin), or piperacillin-tazobactam (Zosyn). Most antibiotics are
administered intravenously or orally for two to six
weeks. Treatment of an eye infection requires local
application of antibiotic drops.
Surgery
Surgical treatment of pseudomonas infections is
sometimes necessary to remove infected and damaged
tissue. Surgery may be required for brain abscesses,
eye infections, bone and joint infections, ear infections, heart infections, and wound infections.
Infected wounds and burns may cause permanent
damage requiring arm or leg amputation.

Prognosis
Most pseudomonas infections can be successfully
treated with antibiotics and surgery. In immunocompromised persons, however, P. aeruginosa infections
have a high mortality rate, particularly following bacteremia or infections of the lower lung. Mortality rates
range from 15 to 20% of patients with severe ear
infections to 89% of patients with infections of the
left side of the heart.

Prevention
Most hospitals have programs for the prevention
of nosocomial infections. Patients with cystic fibrosis
may be given periodic doses of antibiotics to prevent
episodes of pseudomonas pneumonia.
Minor skin infections can be prevented by avoiding hot tubs with cloudy water; avoiding public swimming pools at the end of the day; removing wet
swimsuits as soon as possible; bathing after sharing a
hot tub or using a public pool; cleaning hot tub filters
GALE ENCYCLOPEDIA OF MEDICINE

Bacteremia—Bacterial infection of the blood.
‘‘Hot tub’’ folliculitis—A skin infection caused by
P. aeruginosa that often follows bathing in a hot tub
or public swimming pool.
Immunocompromised—Having a weak immune
system due to disease or the use of certain
medications.
Nosocomial infection—An infection that is
acquired in the hospital.
Opportunistic—Causing disease only under certain conditions, as when a person is already sick
or has a weak immune system.
Pathogen—Any microorganism that produces
disease.

every six weeks; and using appropriate amounts of
chlorine in the water.
Resources
OTHER

Centers for Disease Control. <http://www.cdc.gov/
nccdphp/ddt/ddthome.htm>.

Belinda Rowland, PhD

Pseudomonas pseudomallei infection see
Melioidosis
Pseudost see Strabismus
Pseudotuberculosis see Sarcoidosis

Pseudoxanthoma elasticum
Definition
Pseudoxanthoma elascticum (PXE) is an inherited
connective tissue disorder in which the elastic fibers
present in the skin, eyes, and cardiovascular system
gradually become calcified and inelastic.

Description
PXE was first reported in 1881 by Rigal, but the
defect in elastic fibers was described in 1986 by Darier,
who gave the condition its name. PXE is also known as
GALE ENCYCLOPEDIA OF MEDICINE

Grönblad-Strandberg-Touraine syndrome and systemic elastorrhexis.
The course of PXE varies greatly between individuals. Typically it is first noticed during adolescence as
yellow-orange bumps on the side of the neck. Similar
bumps may appear at other places where the skin
bends a lot, like the backs of the knees and the insides
of the elbows. The skin in these areas tends to get
thick, leathery, inelastic, and acquire extra folds.
These skin problems have no serious consequences,
and for some people, the disease progresses no further.
Bruch’s membrane, a layer of elastic fibers in front
of the retina, becomes calcified in some people with
PXE. Calcification causes cracks in Bruch’s membrane, which can be seen through an ophthalmoscope
as red, brown, or gray streaks called angioid streaks.
The cracks can eventually (e.g., in 10–20 years) cause
bleeding, and the usual resultant scarring leads to
central vision deterioration. However, peripheral
vision is unaffected.
Arterial walls and heart valves contain elastic
fibers that can become calcified. This leads to a greater
susceptibility to the conditions that are associated with
hardening of the arteries in the normal aging population—high blood pressure, heart attack, stroke, and
arterial obstruction—and, similarly, mitral valve prolapse. Heart disease and hypertension associated with
PXE have been reported in children as young as four
to 13 years of age. Although often appearing at a
younger age, the overall incidence of these conditions
is only slightly higher for people with PXE than it is in
the general population.
Arterial inelasticity can lead to bleeding from the
gastrointestinal tract and, rarely, acute vomiting of
blood.
PXE is rare and occurs in about 1 in every 160,000
people in the general population. It is likely, though,
that PXE is underdiagnosed, because of the presence
of mild symptoms in some affected persons and the
lack of awareness of the condition among primary
care physicians.

Causes and symptoms
PXE is caused by changes in the genetic material,
called mutations, that are inherited in either a dominant or recessive mode. A person with the recessive
form of the disease (which is most common) must
possess two copies of the PXE gene to be affected,
and, therefore, must have received one from each
parent. In the dominant form, one copy of the defective gene is sufficient to cause the disease. In some
3075

Pseudoxanthoma elasticum

KEY TERMS

Pseudoxanthoma elasticum

cases, a person with the dominant form inherits the
abnormal gene from a parent with PXE. More commonly, the mutation arises as a spontaneous change in
the genetic material of the affected person. These cases
are called ‘‘sporadic’’ and do not affect parents or
siblings, although each child of a person with sporadic
PXE has a 50% risk to inherit the condition.
Both males and females develop PXE, although
the skin findings seem to be somewhat more common
in females.
The actual genetic causes of this condition were
not discovered until 2000. The recessive, dominant,
and sporadic forms of PXE all appear to be caused
by different mutations or deletions in a single gene
called ABCC6 (also known as MRP6), located on
chromosome 16. Although the responsible gene has
been identified, how it causes PXE is still unknown.
Genetic researchers have since identified mutations in a number of persons with PXE, most of
whom have been found to have the recessive type.
Affected individuals in these families had mutations
in both copies of the gene and parents, who are obligate carriers, had a mutation in only one copy.
Contrary to the usual lack of symptoms in carriers of
recessive genes, some carriers of recessive PXE have
been found to have cardiovascular symptoms typical
of PXE.
Although the recessive type is the most common,
there are also familial and sporadic cases that have
been found to be caused by dominant mutations in the
ABCC6 gene.
A wide range in the type and severity of symptoms
exists between people with PXE. The age of onset also
varies, although most people notice initial symptoms
during adolescence or early adulthood. Often, the first
symptoms to appear are thickened skin with yellow
bumps in localized areas such as the folds of the groin,
arms, knees, and armpits. These changes can also
occur in the mucous membranes, most often in the
inner portion of the lower lip. The appearance of the
skin in PXE has been likened to a plucked chicken or
Moroccan leather.
Angioid streaks in front of the retina are present
in most people with PXE and an ophthalmologic
examination can be used as an initial screen for the
condition. Persons with PXE often complain of sensitivity to light. Because of the progressive breakdown
of Bruch’s membrane, affected persons are at
increased risk for bleeding and scarring of the retina,
which can lead to decreased central vision but does not
usually cause complete blindness.
3076

Calcium deposits in the artery walls contribute to
early-onset atherosclerosis, and another condition
called claudication, inadequate blood flow that results
in pain in the legs after exertion. Abnormal bleeding,
caused by calcification of the inner layer of the
arteries, can occur in the brain, retina, uterus, bladder,
and joints but is most common in the gastrointestinal
tract.

Diagnosis
The presence of calcium in elastic fibers, as
revealed by microscopic examination of biopsied
skin, unequivocally establishes the diagnosis of PXE.

Treatment
PXE cannot be cured, but plastic surgery can treat
PXE skin lesions, and laser surgery is used to prevent
or slow the progression of vision loss. Excessive blood
loss due to bleeding into the gastrointestinal tract or
other organ systems may be treated by transfusion.
Mitral valve prolapse (protrusion of one or both
cusps of the mitral heart valve back into the atrium
during heart beating) can be corrected by surgery, if
necessary.
Measures should be taken to prevent or lessen
cardiovascular complications. People with PXE
should control their cholesterol and blood pressure,
and maintain normal weight. They should exercise for
cardiovascular health and to prevent or reduce claudication later in life. They should also avoid the use of
tobacco, thiazide antihypertensive drugs, blood thinners like coumadin, and nonsteroidal anti-inflammatory drugs like aspirin and ibuprofen. In addition,
they should avoid strain, heavy lifting, and contact
sports, since these activities could trigger retinal and
gastrointestinal bleeding.
People with PXE should have regular eye examinations by an ophthalmologist and report any eye
problems immediately. Regular check-ups with a physician are also recommended, including periodic blood
pressure readings.
Some people have advocated a calcium-restricted
diet, but it is not yet known whether this aids the
problems brought about by PXE. It is known, however, that calcium-restriction can lead to bone
disorders.

Prognosis
The prognosis is for a normal life span with an
increased chance of cardiovascular and circulatory
GALE ENCYCLOPEDIA OF MEDICINE

Angioid streaks—Gray, orange, or red wavy
branching lines in Bruch’s membrane.
Bruch’s membrane—A membrane in the eye
between the choroid membrane and the retina.
Carrier—A person who possesses a gene for an abnormal trait without showing signs of the disorder. The
person may pass the abnormal gene on to offspring.
Claudication—Pain in the lower legs after exercise
caused by insufficient blood supply.
Connective tissue—A group of tissues responsible
for support throughout the body; includes cartilage,
bone, fat, tissue underlying skin, and tissues that
support organs, blood vessels, and nerves throughout the body.
Deletion—The absence of genetic material that is
normally found in a chromosome. Often, the
genetic material is missing due to an error in replication of an egg or sperm cell.
Dominant trait—A genetic trait in which one copy
of the gene is sufficient to yield an outward display
of the trait; dominant genes mask the presence of
recessive genes; dominant traits can be inherited
from a single parent.
Elastic fiber—Fibrous, stretchable connective tissue made primarily from proteins, elastin, collagen,
and fibrillin.
Gene—A building block of inheritance, which
contains the instructions for the production of a
particular protein, and is made up of a molecular
sequence found on a section of DNA. Each gene is
found on a precise location on a chromosome.

role of the ABCC6 protein in elastic fibers may lead to
drugs that will ameliorate or arrest the problems
caused by PXE.
Genetic tests are now available that can provide
knowledge needed to both diagnose PXE in symptomatic persons and predict it prior to the onset of
symptoms in persons at risk. Prenatal diagnosis of
PXE, by testing fetal cells for mutations in the
ABCC6 gene, can be done in early pregnancy by procedures such as amniocentesis or chorionic villus sampling. For most people, PXE is compatible with a
reasonably normal life, and prenatal diagnosis is not
likely to be highly desired.
Genetic testing to predict whether an at-risk child
will develop PXE may be helpful for medical management. A child who is found to carry a mutation can be
monitored more closely for eye problems and bleeding, and can begin the appropriate lifestyle changes to
prevent cardiovascular problems.
Resources
PERIODICALS

Ringpfeil, F., et al. ‘‘Pseudoxanthoma Elasticum: Mutations
in the MRP6 Gene Encoding a Transmembrane AFPbinding Cassette (ABC) Transporter.’’Proceedings of the
National Academy of Sciences 97 (May 2000): 6001–6.
Sherer, D.W., et al. ‘‘Pseudoxanthoma Elasticum: An
Update.’’Dermatology 199 (1999): 3–7.
ORGANIZATIONS

National Association for Pseudoxanthoma Elasticum. 3500
East 12th Avenue, Denver, CO 80206. (303) 355-3866.
Fax: (303) 355-3859. Pxenape@estreet.com. <http://
www.napxe.org>.
PXE International, Inc. 23 Mountain Street, Sharon, MA
02067. (781) 784-3817. Fax: (781) 784-6672.
PXEInter@aol.com. <http://www.pxe.org/>.

Mitral valve—The heart valve that prevents blood
from flowing backwards from the left ventricle into
the left atrium. Also known as bicuspid valve.
Mutation—A permanent change in the genetic
material that may alter a trait or characteristic of
an individual, or manifest as disease, and can be
transmitted to offspring.

Barbara J. Pettersen

Psittacosis see Parrot fever
Psoas abscess see Abscess

Recessive trait—An inherited trait or characteristic
that is outwardly obvious only when two copies of
the gene for that trait are present.

Psoriasis
Definition
problems, hypertension, gastrointestinal bleeding, and
impaired vision. However, now that the gene for PXE
has been identified, the groundwork for research to
provide effective treatment has been laid. Studying the
GALE ENCYCLOPEDIA OF MEDICINE

Named for the Greek word psora meaning ‘‘itch,’’
psoriasis is a chronic, non-contagious disease characterized by inflamed lesions covered with silvery-white
scabs of dead skin.
3077

Psoriasis

KEY TERMS

Psoriasis

Description
Psoriasis, which affects at least four million
Americans, is slightly more common in women than
in men. Although the disease can develop at any time,
10–15% of all cases are diagnosed in children under
10, and the average age at the onset of symptoms is 28.
Psoriasis is most common in fair-skinned people and
extremely rare in dark-skinned individuals.
Normal skin cells mature and replace dead skin
every 28–30 days. Psoriasis causes skin cells to mature
in less than a week. Because the body can’t shed old
skin as rapidly as new cells are rising to the surface,
raised patches of dead skin develop on the arms, back,
chest, elbows, legs, nails, folds between the buttocks,
and scalp.
Psoriasis is considered mild if it affects less than
5% of the surface of the body; moderate, if 5–30% of
the skin is involved, and severe, if the disease affects
more than 30% of the body surface.
Types of psoriasis
Dermatologists distinguish different forms of
psoriasis according to what part of the body is
affected, how severe symptoms are, how long they
last, and the pattern formed by the scales.
PLAQUE PSORIASIS. Plaque psoriasis (psoriasis
vulgaris), the most common form of the disease, is
characterized by small, red bumps that enlarge,
become inflamed, and form scales. The top scales
flake off easily and often, but those beneath the surface of the skin clump together. Removing these scales
exposes tender skin, which bleeds and causes the plaques (inflamed patches) to grow.

Plaque psoriasis can develop on any part of the
body, but most often occurs on the elbows, knees,
scalp, and trunk.
SCALP PSORIASIS. At least 50 of every 100 people
who have any form of psoriasis have scalp psoriasis.
This form of the disease is characterized by scalecapped plaques on the surface of the skull.
NAIL PSORIASIS. The first sign of nail psoriasis is
usually pitting of the fingernails or toenails. Size,
shape, and depth of the marks vary, and affected
nails may thicken, yellow, or crumble. The skin
around an affected nail is sometimes inflamed, and
the nail may peel away from the nail bed.
GUTTATE PSORIASIS. Named for the Latin word

gutta, which means ‘‘a drop,’’ guttate psoriasis is characterized by small, red, drop-like dots that enlarge
rapidly and may be somewhat scaly. Often found on
3078

the arms, legs, and trunk and sometimes in the scalp,
guttate psoriasis can clear up without treatment or
disappear and resurface in the form of plaque
psoriasis.
PUSTULAR PSORIASIS. Pustular psoriasis usually
occurs in adults. It is characterized by blister-like
lesions filled with non-infectious pus and surrounded
by reddened skin. Pustular psoriasis, which can be
limited to one part of the body (localized) or can be
widespread, may be the first symptom of psoriasis or
develop in a patient with chronic plaque psoriasis.

Generalized pustular psoriasis is also known as
Von Zumbusch pustular psoriasis. Widespread,
acutely painful patches of inflamed skin develop suddenly. Pustules appear within a few hours, then dry
and peel within two days.
Generalized pustular psoriasis can make lifethreatening demands on the heart and kidneys.
Palomar-plantar pustulosis (PPP) generally
appears between the ages of 20 and 60. PPP causes
large pustules to form at the base of the thumb or on
the sides of the heel. In time, the pustules turn brown
and peel. The disease usually becomes much less active
for a while after peeling.
Acrodermatitis continua of Hallopeau is a form of
PPP characterized by painful, often disabling, lesions
on the fingertips or the tips of the toes. The nails may
become deformed, and the disease can damage bone in
the affected area.
INVERSE PSORIASIS. Inverse psoriasis occurs in the
armpits and groin, under the breasts, and in other
areas where skin flexes or folds. This disease is characterized by smooth, inflamed lesions and can be
debilitating.
ERYTHRODERMIC PSORIASIS. Characterized by
severe scaling, itching, and pain that affects most of
the body, erythrodermic psoriasis disrupts the body’s
chemical balance and can cause severe illness. This
particularly inflammatory form of psoriasis can be
the first sign of the disease, but often develops in
patients with a history of plaque psoriasis.
PSORIATIC ARTHRITIS. About 10% of partients
with psoriasis develop a complication called psoriatic
arthritis. This type of arthritis can be slow to develop
and mild, or it can develop rapidly. Symptoms of
psoriatic arthritis include:


joint discomfort, swelling, stiffness, or throbbing



swelling in the toes and ankles



pain in the digits, lower back, wrists, knees, and ankles



eye inflammation or pink eye (conjunctivitis)
GALE ENCYCLOPEDIA OF MEDICINE

Psoriasis

Causes and symptoms
The cause of psoriasis is unknown, but research
suggests that an immune-system malfunction triggers
the disease. Factors that increase the risk of developing psoriasis include:


family history



stress



exposure to cold temperatures



injury, illness, or infection



steroids and other medications



race

Trauma and certain bacteria may trigger psoriatic
arthritis in patients with psoriasis.

Diagnosis
A complete medical history and examination of
the skin, nails, and scalp are the basis for a diagnosis of
psoriasis. In some cases, a microscopic examination
of skin cells is also performed.
Blood tests can distinguish psoriatic arthritis from
other types of arthritis. Rheumatoid arthritis, in particular, is diagnosed by the presence of a particular
antibody present in the blood. That antibody is not
present in the blood of patients with psoriatic arthritis.

Treatment
Age, general health, lifestyle, and the severity and
location of symptoms influence the type of treatment
used to reduce inflammation and decrease the rate at
which new skin cells are produced. Because the course
of this disease varies with each individual, doctors
must experiment with or combine different treatments
to find the most effective therapy for a particular
patient.
Mild-moderate psoriasis
Steroid creams and ointments are commonly used
to treat mild or moderate psoriasis, and steroids are
sometimes injected into the skin of patients with a
limited number of lesions. In mid-1997, the United
States Food and Drug Administration (FDA)
approved the use of tazarotene (Tazorac) to treat
mild-to-moderate plaque psoriasis. This water-based
gel has chemical properties similar to vitamin A.
Brief daily doses of natural sunlight can significantly relieve symptoms. Sunburn has the opposite
effect.
GALE ENCYCLOPEDIA OF MEDICINE

Psoriasis, a chronic skin disorder, may appear on any area of
the body, including the elbow, as shown above. (Photo
Researchers, Inc. Reproduced by permission.)

Moisturizers and bath oils can loosen scales,
soften skin, and may eliminate the itch. So can adding
a cup of oatmeal to a tub of bath water. Salicylic acid
(an ingredient in aspirin) can be used to remove dead
skin or increase the effectiveness of other therapies.
Moderate psoriasis
Administered under medical supervision, ultraviolet light B (UVB) is used to control psoriasis that
covers many areas of the body or that has not
responded to topical preparations. Doctors combine
UVB treatments with topical medications to treat
some patients and sometimes prescribe home phototherapy, in which the patient administers his or her
own UVB treatments.
Photochemotherapy (PUVA) is a medically
supervised procedure that combines medication with
exposure to ultraviolet light (UVA) to treat localized
or widespread psoriasis. An individual with widespread psoriasis that has not responded to treatment
may enroll in one of the day treatment programs conducted at special facilities throughout the United
States. Psoriasis patients who participate in these
intensive sessions are exposed to UVB and given
other treatments for six to eight hours a day for two
to four weeks.
Severe psoriasis
Methotrexate (MTX) can be given as a pill or as
an injection to alleviate symptoms of severe psoriasis
or psoriatic arthritis. Patients who take MTX must be
carefully monitored to prevent liver damage.
Psoriatic arthritis can also be treated with non
steroidal anti-inflammatory drugs (NSAID), like
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Psoriasis

acetaminophen (Tylenol) or aspirin. Hot compresses
and warm water soaks may also provide some relief
for painful joints.
Other medications used to treat severe psoriasis
include etrentinate (Tegison) and isotretinoin
(Accutane), whose chemical properties are similar to
those of vitamin A. Most effective in treating pustular
or erythrodermic psoriasis, Tegison also relieves some
symptoms of plaque psoriasis. Tegison can enhance
the effectiveness of UVB or PUVA treatments and
reduce the amount of exposure necessary.
Accutane is a less effective psoriasis treatment
than Tegison, but can cause many of the same side
effects, including nosebleeds, inflammation of the eyes
and lips, bone spurs, hair loss, and birth defects.
Tegison is stored in the body for an unknown length
of time, and should not be taken by a woman who is
pregnant or planning to become pregnant. A woman
should use reliable birth control while taking
Accutane and for at least one month before and after
her course of treatment.
Cyclosporin emulsion (Neoral) is used to treat stubborn cases of severe psoriasis. Cyclosporin is also used to
prevent rejection of transplanted organs, and Neoral,
approved by the FDA in 1997, should be particularly
beneficial to psoriasis patients who are young children or
African-Americans, or those who have diabetes.
Other conventional treatments for psoriasis
include:


Capsaicin (Capsicum frutecens), an ointment that can
stop production of the chemical that causes the skin
to become inflamed and halts the runaway production of new skin cells. Capsaicin is available without
a prescription, but should be used under a doctor’s
supervision to prevent burns and skin damage.



Hydrocortisone creams, topical ointments containing a form of vitamin D called calcitriol, and coal-tar
shampoos and ointments can relieve symptoms.
Hydrocortisone creams have been associated with
such side effects as folliculitis (inflammation of the
hair follicles), while coal-tar preparations have been
associated with a heightened risk of skin cancer.

Alternative treatment
Non-traditional psoriasis treatments include:


Soaking in warm water and German chamomile
(Matricaria recutita) or bathing in warm salt water.



Drinking as many as three cups a day of hot tea made
with one or a combination of the following herbs:
burdock (Arctium lappa) root, dandelion

3080

KEY TERMS
Arthritis—An inflammation of joints.

(Taraxacum mongolicum) root, Oregon grape
(Mahonia aquifolium), sarsaparilla (Smilax officinalis), and balsam pear (Momardica charantia).


Taking two 500-mg capsules of evening primrose oil
(Oenothera biennis) a day. Pregnant women should
not use evening primrose oil, and patients with liver
disease or high cholesterol should use it only under a
doctor’s supervision.



Eating a diet that includes plenty of fish, turkey,
celery (for cleansing the kidneys), parsley, lettuce,
lemons (for cleansing the liver), limes, fiber, and
fruit and vegetable juices.



Eating a diet that eliminates animal products high in
saturated fats, since they promote inflammation.



Drinking plenty of water (at least eight glasses) each
day.



Taking nutritional supplements including folic acid,
lecithin, vitamin A (specific for the skin), vitamin E,
selenium, and zinc.



Regularly imagining clear, healthy skin.

Other helpful alternative approaches include identifying and eliminating food allergens from the diet,
enhancing the fuction of the liver, augmenting the
hydrochloric acid in the stomach, and completing a
detoxification program. Constitutional homeopathic
treatment, if properly prescribed, can also help resolve
psoriasis.

Prognosis
Most cases of psoriasis can be controlled, and
most people who have psoriasis can live normal lives.
Some people who have psoriasis are so self conscious and embarrassed about their appearance that
they become depressed and withdrawn. The Social
Security Administration grants disability benefits to
about 400 psoriasis patients each year, and a comparable number die from complications of the disease.

Prevention
A doctor should be notified if:


psoriasis symptoms appear or reappear after
treatment
GALE ENCYCLOPEDIA OF MEDICINE

pustules erupt on the skin and the patient experiences
fatigue, muscle aches, and fever



unfamiliar, unexplained symptoms appear.

people and 1 in 2 people with psoriasis may also have
some arthritis symptoms.

Causes and symptoms

Resources
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
American Skin Association, Inc. 150 E. 58th St., 3rd floor,
New York, NY 10155-0002. (212) 688-6547.
National Psoriasis Foundation. 6600 S.W. 92nd Ave., Suite
300, Portland, OR 97223. (800) 723-9166. <http://
www.psoriasis.org>.

Maureen Haggerty

Psoriatic arthritis

The cause of psoriatic arthritis is unknown. As in
psoriasis, genetic factors appear to be involved. People
with psoriatic arthritis are more likely than others to
have close relatives with the disease, but they are just
as likely to have relatives with psoriasis but no joint
disease. Researchers believe genes increasing the susceptibility to developing psoriasis may be located on
chromosome 6p and chromosome 17, but the specific
genetic abnormality has not been identified. Like psoriasis and other forms of arthritis, psoriatic arthritis
also appears to be an autoimmune disorder, triggered
by an attack of the body’s own immune system on
itself.
Symptoms of psoriatic arthritis include dry, scaly,
silver patches of skin combined with joint pain and
destructive changes in the feet, hands, knees, and
spine. Tendon pain and nail deformities are other hallmarks of psoriatic arthritis.

Definition
Psoriatic arthritis is a form of arthritic joint disease associated with the chronic skin scaling and fingernail changes seen in psoriasis.

Description
Physicians recognize a number of different forms
of psoriatic arthritis. In some patients, the arthritic
symptoms will affect the small joints at the ends of the
fingers and toes. In others, symptoms will affect
joints on one side of the body but not on the other.
In addition, there are patients whose larger joints on
both sides of the body simultaneously become
affected, as in rheumatoid arthritis. Some people
with psoriatic arthritis experience arthritis symptoms
in the back and spine; in rare cases, called psoriatic
arthritis mutilans, the disease destroys the joints and
bones, leaving patients with gnarled and club-like
hands and feet. In many patients, symptoms of psoriasis precede the arthritis symptoms; a clue to possible joint disease is pitting and other changes in the
fingernails.
Most people develop psoriatic arthritis at ages 35–
45, but it has been observed earlier in adults and
children. Both the skin and joint symptoms will come
and go; there is no clear relationship between the
severity of the psoriasis symptoms and arthritis pain
at any given time. It is unclear how common psoriatic
arthritis is. Recent surveys suggest that between 1 in 5
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Skin and nail changes characteristic of psoriasis
with accompanying arthritic symptoms are the hallmarks of psoriatic arthritis. A blood test for rheumatoid factor, antibodies that suggest the presence of
rheumatoid arthritis, is negative in nearly all patients
with psoriatic arthritis. X rays may show characteristic
damage to the larger joints on either side of the body
as well as fusion of the joints at the ends of the fingers
and toes.

Treatment
Treatment for psoriatic arthritis is meant to
control the skin lesions of psoriasis and the joint
inflammation of arthritis. Nonsteroidal anti-inflammatory drugs, gold salts, and sulfasalazine are standard arthritis treatments, but have no effect on
psoriasis. Antimalaria drugs and systemic corticosteroids should be avoided because they can cause
dermatitis or exacerbate psoriasis when they are
discontinued.
Several treatments are useful for both the skin
lesions and the joint inflammation of psoriatic arthritis. Etretinate, a vitamin A derivative; methotrexate, a
potent suppressor of the immune system; and ultraviolet light therapy have all been successfully used to
treat psoriatic arthritis.
3081

Psoriatic arthritis



Psychiatric confinement

Resources

KEY TERMS
Psoriasis—A common recurring skin disease that is
marked by dry, scaly, and silvery patches of skin
that appear in a variety of sizes and locations on the
body.
Psoriatic arthritis mutilans—A severe form of
psoriatic arthritis that destroys the joints of the
fingers and toes and causes the bones to fuse,
leaving patients with gnarled and club-like hands
and feet.
Rheumatoid arthritis—A systemic disease that primarily affects the joints, causing inflammation,
changes in structure, and loss of function.
Rheumatoid factor—A series of antibodies that signal the presence of rheumatoid arthritis. May also
be present in Sjögren’s syndrome and systemic
lupus erythematosus, among others.

Alternative treatment
Food allergies/intolerances are believed to play a
role in most autoimmune disorders, including psoriatic
arthritis. Identification and elimination of food allergens from the diet can be helpful. Constitutional
homeopathy can work deeply and effectively with
this condition, if the proper prescription is given.
Acupuncture, Chinese herbal medicine, and western
herbal medicine can all be useful in managing the
symptoms of psoriatic arthritis. Nutritional supplements can contribute added support to the healing
process. Alternative treatments recommended for
psoriasis and rheumatoid arthritis may also be helpful
in treating psoriatic arthritis.

Prognosis
The prognosis for most patients with psoriatic
arthritis is good. For many the joint and other
arthritis symptoms are much milder than those
experienced in rheumatoid arthritis. One in five
people with psoriatic arthritis, however, face potentially crippling joint disease. In some cases, the
course of the arthritis can be far more mutilating
than in rheumatoid arthritis.

Prevention
There are no preventive measures for psoriatic
arthritis.
3082

ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
The American College of Rheumatology. 1800 Century
Place, Suite 250, Atlanta, GA 30345. (404) 633-3777.
<http://www.rheumatology.org>.

Richard H. Camer

PSP see Progressive supranuclear palsy

Psychiatric confinement
Definition
Psychiatric confinement is the use of restraints
to detain a person in need of care and further
evaluation.

Purpose
The purpose of restraint and confinement are crucial since they have a medico legal implication. The
primary purpose for such intervention is typically an
urgent or emergent condition that could cause danger
to the affected person or others, or cause severe disability to the extent whereby the affected person is
unable to care for his/herself.

Precautions
Clinicians utilizing this form of patient and public
safety should perform a comprehensive mental status
examination and document the findings. This
approach can potentially provide clear records establishing the specific presenting problems and symptoms
that can lead to ambiguities and potential legal action.

Description
Confinement with restraints can be categorized as
urgent or emergent. Emergent causes can include
patients exhibiting abnormal vital signs (breathing,
pulse rate, temperature, blood pressure), threatening or
violent behavior, and those who present with signs and
symptoms of alcohol or illicit drug intoxication. Urgent
use of confinement is indicated in patients showing suicidal thoughts, extreme anxiety, homicidal tendencies,
violence, or a danger to self or the public at large.
GALE ENCYCLOPEDIA OF MEDICINE

Those categorized as emergent should be prepared for further testing that can include blood chemistry and psychological assessment and evaluation.
Initially the patient is restrained with four point
leather restraints (both arms and both legs) and placed
in a quiet room with a sitter. For those with urgent
needs, restraint is initiated and initial management is
directed to assess for an underlying medical cause and
address psychological needs.

Aftercare
Further assessment, testing, and evaluation is
necessary for a definitive diagnosis and devising an
appropriate treatment plan.

Risks
A deficiency in record-keeping can lead to legal
problems. The criteria and specifications for confinement should be clearly indicated. Meticulous clinical
examination and documentation is essential for a definitive diagnosis. Persons who are confined due to substance abuse problems may have legal issues. As of 2001
there is proposed legislation concerning the misuse of
restraints for psychiatric inpatients, which in the past
has been responsible for numerous wrongful deaths.
There are currently no federal laws that regulate the
use of inpatient restraints nor any requirements for
reporting injuries or death.
Resources
PERIODICALS

Reeves,R., et al. ‘‘Medicolegal Errors in the ED Related to the
Involuntary Confinement of Psychiatric Patients.’’
American Journal of EmergencyMedicine November 1998.

Laith Farid Gulli, M.D.
Catherine Seeley
Keith Tatarelli, J.D.

Psychoanalysis
Definition
Psychoanalysis is a form of psychotherapy used by
qualified psychotherapists to treat patients who have a
range of mild to moderate chronic life problems. It is
related to a specific body of theories about the
GALE ENCYCLOPEDIA OF MEDICINE

relationships between conscious and unconscious mental processes, and should not be used as a synonym for
psychotherapy in general. Psychoanalysis is done oneon-one with the patient and the analyst; it is not appropriate for group work.

Purpose
Psychoanalysis is the most intensive form of an
approach to treatment called psychodynamic therapy. Psychodynamic refers to a view of human personality that results from interactions between
conscious and unconscious factors. The purpose of
all forms of psychodynamic treatment is to bring
unconscious mental material and processes into full
consciousness so that the patient can gain more control over his or her life.
Classical psychoanalysis has become the least
commonly practiced form of psychodynamic therapy
because of its demands on the patient’s time, as well
as on his or her emotional and financial resources. It
is, however, the oldest form of psychodynamic treatment. The theories that underlie psychoanalysis were
worked out by Sigmund Freud (1856–1939), a
Viennese physician, during the early years of the
twentieth century. Freud’s discoveries were made in
the context of his research into hypnosis. The goal of
psychoanalysis is the uncovering and resolution of
the patient’s internal conflicts. The treatment focuses
on the formation of an intense relationship between
the therapist and patient, which is analyzed and discussed in order to deepen the patient’s insight into
his or her problems.
Psychoanalytic psychotherapy is a modified form
of psychoanalysis that is much more widely practiced.
It is based on the same theoretical principles as psychoanalysis, but is less intense and less concerned with
major changes in the patient’s character structure. The
focus in treatment is usually the patient’s current life
situation and the way problems relate to early conflicts
and feelings, rather than an exploration of the unconscious aspects of the relationship that has been formed
with the therapist.
Not all patients benefit from psychoanalytic treatment. Potential patients should meet the following
prerequisites:


The capacity to relate well enough to form an effective working relationship with the analyst. This relationship is called a therapeutic alliance.



At least average intelligence and a basic understanding of psychological theory.
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Psychoanalysis

Preparation

Psychoanalysis

C A R L G U S T A V J U N G (1875–1961)
Jung exhibited an interest in many diverse areas of study
but finally decided to pursue medicine at the University of
Basel and the University of Zurich, earning his degree in
1902. He also studied psychology in Paris. In 1903, Jung
married Emma Rauschenbach, his companion and collaborator. The couple had five children.
Jung’s professional career began in 1900 at the
University of Zurich where he worked as an assistant to
Eugene Blueler in the psychiatric clinic. During his internship, he and some co-workers used an experiment that
revealed groups of ideas in the unconscious psyche
which he named complexes. Jung sent his publication
Studies in Word Association (1904) to Sigmund Freud
after finding his own beliefs confirmed by Freud’s work.
Jung and Freud became friends and collaborators until
1913 when Jung’s ideas began to conflict with Freud’s.
During the time following this split, Jung published Two
Essays on Analytical Psychology (1916, 1917) and
Psychological Types (1921). Jung’s later work developed
from the concepts in his Two Essays publication and he
became known as a founder of modern depth psychology.
(Library of Congress.)

Carl Gustav Jung was born in Kesswil, Switzerland,
on July 26, 1875, to a Protestant clergyman who moved
his family to Basel when Jung was four. While growing up,



The ability to tolerate frustration, sadness, and other
painful emotions.



The capacity to distinguish between reality and
fantasy.

People considered best suited to psychoanalytic
treatment include those with depression, character
disorders, neurotic conflicts, and chronic relationship
problems. When the patient’s conflicts are long-standing and deeply entrenched in his or her personality,
psychoanalysis may be preferable to psychoanalytic
psychotherapy, because of its greater depth.

Precautions
Psychoanalysis is not usually considered suitable
for patients suffering from severe depression or such
psychotic disorders as schizophrenia, although some
analysts have successfully treated patients with psychoses. It is also not appropriate for people with
addictions or substance dependency, disorders of
aggression or impulse control, or acute crises; some
of these people may benefit from psychoanalysis after
the crisis has been resolved.
3084

In 1944, Jung gave up his psychological practice and
his explorations after he suffered a severe heart attack. Jung
received honorary doctorates from numerous universities
and in 1948 he founded the C. G. Jung Institute in Zurich.
Jung died on June 6, 1961.

Description
In both psychoanalysis and psychoanalytic psychotherapy, the therapist does not tell the patient how
to solve problems or offer moral judgments. The focus
of treatment is exploration of the patient’s mind and
habitual thought patterns. Such therapy is termed
‘‘non-directed.’’ It is also ‘‘insight-oriented,’’ meaning
that the goal of treatment is increased understanding
of the sources of one’s inner conflicts and emotional
problems. The basic techniques of psychoanalytical
treatment include:
Therapist neutrality
Neutrality means that the analyst does not take
sides in the patient’s conflicts, express feelings about
the patient, or talk about his or her own life. Therapist
neutrality is intended to help the patient stay focused
on issues rather than be concerned with the therapist’s
reactions. In psychoanalysis, the patient lies on a
couch facing away from the therapist. In psychodynamic psychotherapy, however, the patient and therapist usually sit in comfortable chairs facing each other.
GALE ENCYCLOPEDIA OF MEDICINE

Free association means that the patient talks
about whatever comes into mind without censoring
or editing the flow of ideas or memories. Free
association allows the patient to return to earlier
or more childlike emotional states (‘‘regress’’).
Regression is sometimes necessary in the formation
of the therapeutic alliance. It also helps the analyst
to understand the recurrent patterns of conflict in
the patient’s life.
Therapeutic alliance and transference
Transference is the name that psychoanalysts
use for the patient’s repetition of childlike ways of
relating that were learned in early life. If the therapeutic alliance has been well established, the
patient will begin to transfer thoughts and feelings
connected with siblings, parents, or other influential figures to the therapist. Discussing the transference helps the patient gain insight into the ways
in which he or she misreads or misperceives other
people in present life.
Interpretation
In psychoanalytic treatment, the analyst is silent
as much as possible, in order to encourage the
patient’s free association. However, the analyst
offers judiciously timed interpretations, in the form
of verbal comments about the material that emerges
in the sessions. The therapist uses interpretations in
order to uncover the patient’s resistance to treatment, to discuss the patient’s transference feelings,
or to confront the patient with inconsistencies.
Interpretations may be either focused on present
issues (‘‘dynamic’’) or intended to draw connections
between the patient’s past and the present
(‘‘genetic’’). The patient is also often encouraged to
describe dreams and fantasies as sources of material
for interpretation.
Working through
‘‘Working through’’ occupies most of the work
in psychoanalytic treatment after the transference
has been formed and the patient has begun to
acquire insights into his or her problems.
Working through is a process in which the new
awareness is repeatedly tested and ‘‘tried on for
size’’ in other areas of the patient’s life. It allows
the patient to understand the influence of the past
on his or her present situation, to accept it emotionally as well as intellectually, and to use the new
understanding to make changes in present life.
GALE ENCYCLOPEDIA OF MEDICINE

Working through thus helps the patient to gain
some measure of control over inner conflicts and
to resolve them or minimize their power.
Although psychoanalytic treatment is primarily
verbal, medications are sometimes used to stabilize
patients with severe anxiety, depression, or other
mood disorders during the analysis.
The cost of either psychoanalysis or psychoanalytic psychotherapy is prohibitive for most patients
without insurance coverage. A full course of psychoanalysis usually requires three to five weekly sessions
with a psychoanalyst over a period of three to five
years. A course of psychoanalytic psychotherapy
involves one to three meetings per week with the
therapist for two to five years. Each session or meeting
typically costs between $80 and $200, depending on
the locale and the experience of the therapist. The
increasing reluctance of most HMOs and other managed care organizations to pay for long-term psychotherapy is one reason that these forms of
treatment are losing ground to short-term methods
of treatment and the use of medications to control
the patient’s emotional symptoms. It is also not clear
as of 2003 that long-term psychoanalytically oriented
approaches are more beneficial than briefer therapy
methods for many patients. On the other hand,
patients who can benefit from a psychoanalytic
approach but cannot afford private fees may wish to
contact the American Psychoanalytic Association,
which maintains a list of analysts in training who
offer treatment for reduced fees.

Preparation
Some patients may need evaluation for possible
medical problems before entering psychoanalysis
because numerous diseases—including virus infections and certain vitamin deficiencies—have emotional side effects or symptoms. The therapist will
also want to know whether the patient is taking any
prescription medications that may affect the patient’s
feelings or ability to concentrate. In addition, it is
important to make sure that the patient is not abusing
drugs or alcohol.

Risks
The primary risk to the patient is related to the
emotional pain resulting from new insights and
changes in long-standing behavior patterns. In some
patients, psychoanalysis produces so much anxiety
that they cannot continue with this treatment method.
In other cases, the therapist’s lack of skill or
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Psychoanalysis

Free association

Psychological tests

KEY TERMS
Free association—A technique used in psychoanalysis in which the patient allows thoughts and feelings to emerge without trying to organize or censor
them.
Interpretation—A verbal comment made by the
analyst in response to the patient’s free association.
It is intended to help the patient gain new insights.
Neurosis—A mental and emotional disorder that
affects only part of the personality and is accompanied by a significantly less distorted perception
of reality than in psychosis.
Psychodynamic—An approach to psychotherapy
based on the interplay of conscious and unconscious
factors
in
the
patient’s
mind.
Psychoanalysis is one type of psychodynamic
therapy.
Regression—The process in which the patient
reverts to earlier or less mature feelings and
behaviors.
Therapeutic alliance—The working relationship
between a therapist and a patient that is necessary
to the success of therapy.
Transference—The process that develops during
psychoanalytic work during which the patient
redirects feelings about early life figures toward
the analyst.
Working through—The repeated testing of insights,
which takes up most of the work in psychoanalysis
after the therapeutic alliance has been formed.

Attempts to compare the effectiveness of psychoanalytical treatment to other modes of therapy are
difficult to evaluate. Some aspects of Freudian theory
have been questioned since the 1970s on the grounds
of their limited applicability to women and to people
from non-Western cultures. In particular, some psychiatrists with cross-cultural experience maintain that
psychoanalysis presupposes a highly individualistic
Western concept of human personhood that is alien
to traditional Asian and African societies. There is,
however, general agreement that psychoanalytic
approaches work well for certain types of patients,
specifically those with neurotic conflicts.
Resources
PERIODICALS

Blass, R. B. ‘‘On Ethical Issues at the Foundation of the
Debate Over the Goals of Psychoanalysis.’’
International Journal of Psychoanalysis 84 (August
2003): 929–943.
Gabbard, G. O., and D. Westen. ‘‘Rethinking Therapeutic
Action.’’ International Journal of Psychoanalysis 84
(August 2003): 823–841.
Lombardi, R. ‘‘Mental Models and Language Registers in
the Psychoanalysis of Psychosis: An Overview of a
Thirteen-Year Analysis.’’ International Journal of
Psychoanalysis 84 (August 2003): 843–863.
Roland, A. ‘‘Psychoanalysis Across Civilizations: A
Personal Journey.’’ Journal of the American Academy of
Psychoanalysis and Dynamic Psychiatry 31 (Summer
2003): 275–295.
ORGANIZATIONS

American Psychoanalytic Association. 309 East 49th Street,
New York, NY 10017. (212) 752-0450. <http://
www.apsa-co.org>.

Rebecca J. Frey, PhD
differences in cultural background may prevent the
formation of a solid therapeutic alliance.

Normal results
Psychoanalysis and psychoanalytic psychotherapy both have the goal of basic changes in the patient’s
personality structure and level of functioning,
although psychoanalysis typically aims at more extensive and more profound change. In general, this
approach to treatment is considered successful if the
patient has shown:


reduction in intensity or number of symptoms



some resolution of basic emotional conflicts



increased independence and self-esteem



improved functioning and adaptation to life

3086

Psychological tests
Definition
Psychological tests are written, visual, or verbal
evaluations administered to assess the cognitive and
emotional functioning of children and adults.

Purpose
Psychological tests are used to assess a variety of
mental abilities and attributes, including achievement
and ability, personality, and neurological functioning.
GALE ENCYCLOPEDIA OF MEDICINE

For children, academic achievement, ability, and
intelligence tests may be used as a tool in school placement, in determining the presence of a learning disability or a developmental delay, in identifying
giftedness, or in tracking intellectual development.
Intelligence testing may be used with adults to determine vocational ability (e.g., in career counseling) or
to assess adult intellectual ability in the classroom.
Personality tests
Personality tests are administered for a wide variety of reasons, from diagnosing psychopathology
(e.g., personality disorder, depressive disorder) to
screening job candidates. They may be used in an
educational or vocational setting to determine personality strengths and weaknesses, or in the legal system
to evaluate parolees.
Neuropsychological tests
Patients who have experienced a traumatic brain
injury, brain damage, or organic neurological problems (for example, dementia) are administered neuropsychological tests to assess their level of
functioning and identify areas of mental impairment.
They may also be used to evaluate the progress of a
patient who has undergone treatment or rehabilitation
for a neurological injury or illness. In addition, certain
neuropsychological measures may be used to screen
children for developmental delays and/or learning
disabilities.

Precautions
Psychological testing requires a clinically trained
examiner. All psychological tests should be administered, scored, and interpreted by a trained professional, preferably a psychologist or psychiatrist with
expertise in the appropriate area.
Psychological tests are only one element of a psychological assessment. They should never be used
alone as the sole basis for a diagnosis. A detailed
history of the test subject and a review of psychological, medical, educational, or other relevant records are
required to lay the groundwork for interpreting the
results of any psychological measurement.
Cultural and language differences in the test subject may affect test performance and may result in
inaccurate test results. The test administrator should
be informed before psychological testing begins if the
test taker is not fluent in English and/or belongs to a
GALE ENCYCLOPEDIA OF MEDICINE

minority culture. In addition, the subject’s motivation
and motives may also affect test results.

Description
Psychological tests are formalized measures of
mental functioning. Most are objective and quantifiable; however, certain projective tests may involve
some level of subjective interpretation. Also known
as inventories, measurements, questionnaires, and
scales, psychological tests are administered in a variety
of settings, including preschools, primary and secondary schools, colleges and universities, hospitals, outpatient healthcare settings, social agencies, prisons,
and employment or human resource offices. They
come in a variety of formats, including written, verbal,
and computer administered.
Achievement and ability tests
Achievement and ability tests are designed to
measure the level of an individual’s intellectual functioning and cognitive ability. Most achievement and
ability tests are standardized, meaning that norms
were established during the design phase of the test
by administering the test to a large representative
sample of the test population. Achievement and ability
tests follow a uniform testing protocol, or procedure
(i.e., test instructions, test conditions, and scoring
procedures) and their scores can be interpreted in
relation to established norms. Common achievement
and ability tests include the Wechsler intelligence test
(WISC-III and WAIS) and the Stanford-Binet intelligence scales.
Personality tests
Personality tests and inventories evaluate the
thoughts, emotions, attitudes, and behavioral traits
that comprise personality. The results of these tests
determine an individual’s personality strengths and
weaknesses, and may identify certain disturbances
in personality, or psychopathology. Tests such as the
Minnesota multiphasic personality inventory MMPI-2)
and the Millon clinical multiaxial Inventory III
(MMPI-III), are used to screen individuals for specific psychopathologies or emotional problems.
Another type of personality test is the projective
personality assessment. A projective test asks a subject
to interpret some ambiguous stimuli, such as a series of
inkblots. The subject’s responses provide insight into
his or her thought processes and personality traits. For
example, the Rorschach inkblot test and the Holtzman
ink blot test (HIT) use a series of inkblots that the test
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Psychological tests

Achievement and ability tests

Psychosis

Normal results

KEY TERMS
Norms—A fixed or ideal standard; normative or
mean score for a particular age group.
Psychopathology—A mental disorder or illness,
such as schizophrenia, personality disorder, or
major depressive disorder.
Quantifiable—Can be expressed as a number. The
results of quantifiable psychological tests can be
translated into numerical values, or scores.
Representative sample—A random sample of people that adequately represent the test taking population in age, gender, race, and socioeconomic
standing.
Standardization—The process of determining
established norms and procedures for a test to
act as a standard reference point for future test
results.

subject is asked to identify. Another projective assessment, the Thematic apperception test (TAT), asks
the subject to tell a story about a series of pictures.
Some consider projective tests to be less reliable than
objective personality tests. If the examiner is not welltrained in psychometric evaluation, subjective interpretations may affect the evaluation of these tests.
Neuropsychological tests
Many insurance plans cover all or a portion of
diagnostic neuropsychological or psychological testing. As of 1997, Medicare reimbursed for psychological and neuropsychological testing. Billing time
typically includes test administration, scoring and
interpretation, and reporting.

Preparation
Prior to the administration of any psychological
test, the administrator should provide the test subject
with information on the nature of the test and its
intended use, complete standardized instructions for
taking the test (including any time limits and penalties
for incorrect responses), and information on the confidentiality of the results. After these disclosures are
made, informed consent should be obtained from the
test subject before testing begins (except in cases of
legally mandated testing, where consent is not
required of the subject).
3088

All psychological and neuropsychological assessments should be administered, scored, and interpreted
by a trained professional. When interpreting test
results for test subjects, the test administrator will
review with subjects: what the test evaluates, its precision in evaluation, any margins of error involved in
scoring, and what the individual scores mean in the
context of overall test norms and the background of
the test subject.
Resources
ORGANIZATIONS

American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.

Paula Anne Ford-Martin

Psychosis
Definition
Psychosis is a symptom or feature of mental illness
typically characterized by radical changes in personality, impaired functioning, and a distorted or nonexistent sense of objective reality.

Description
Patients suffering from psychosis have impaired
reality testing; that is, they are unable to distinguish
personal subjective experience from the reality of the
external world. They experience hallucinations and/or
delusions that they believe are real, and may behave
and communicate in an inappropriate and incoherent
fashion. Psychosis may appear as a symptom of a
number of mental disorders, including mood and personality disorders. It is also the defining feature of
schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, and the psychotic
disorders (i.e., brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general
medical condition, and substance-induced psychotic
disorder).

Causes and symptoms
Psychosis may be caused by the interaction of
biological and psychosocial factors depending on the
GALE ENCYCLOPEDIA OF MEDICINE

Biological factors that are regarded as contributing to the development of psychosis include genetic
abnormalities and substance use. With regard to chromosomal abnormalities, studies indicate that 30% of
patients diagnosed with a psychotic disorder have a
microdeletion at chromosome 22q11. Another group
of researchers has identified the gene G72/G30 at
chromosome 13q33.2 as a susceptibility gene for childhood-onset schizophrenia and psychosis not otherwise
specified.
With regard to substance abuse, several different
research groups reported in 2004 that cannabis
(marijuana) use is a risk factor for the onset of
psychosis.
Migration is a social factor that influences people’s
susceptibility
to
psychotic
disorders.
Psychiatrists in Europe have noted the increasing
rate of schizophrenia and other psychotic disorders
among immigrants to almost all Western European
countries. Black immigrants from Africa or the
Caribbean appear to be especially vulnerable. The
stresses involved in migration include family breakup,
the need to adjust to living in large urban areas, and
social inequalities in the new country.
Schizophrenia, schizophreniform disorder, and
schizoaffective disorder
Psychosis in schizophrenia and perhaps schizophreniform disorder appears to be related to abnormalities in the structure and chemistry of the brain, and
appears to have strong genetic links; but its course and
severity can be altered by social factors such as stress
or a lack of support within the family. The cause of
schizoaffective disorder is less clear cut, but biological
factors are also suspected.
Delusional disorder
The exact cause of delusional disorder has not
been conclusively determined, but potential causes
include heredity, neurological abnormalities, and
changes in brain chemistry. Some studies have indicated that delusions are generated by abnormalities in
the limbic system, the portion of the brain on the inner
edge of the cerebral cortex that is believed to regulate
emotions. Delusional disorder is also more likely to
develop in persons who are isolated from others in
their society by language difficulties and/or cultural
differences.
GALE ENCYCLOPEDIA OF MEDICINE

Brief psychotic disorder
Trauma and stress can cause a short-term psychosis (less than a month’s duration) known as brief psychotic disorder. Major life-changing events such as the
death of a family member or a natural disaster have
been known to stimulate brief psychotic disorder in
patients with no prior history of mental illness.
Psychotic disorder due to a general medical
condition
Psychosis may also be triggered by an organic
cause, termed a psychotic disorder due to a general
medical condition. Organic sources of psychosis
include neurological conditions (for example, epilepsy
and cerebrovascular disease), metabolic conditions
(for example, porphyria), endocrine conditions (for
example, hyper- or hypothyroidism), renal failure, electrolyte imbalance, or autoimmune disorders.
Substance-induced psychotic disorder
Psychosis is also a known side effect of the use,
abuse, and withdrawal from certain drugs. So-called
recreational drugs, such as hallucinogenics, PCP,
amphetamines, cocaine, marijuana, and alcohol, may
cause a psychotic reaction during use or withdrawal.
Certain prescription medications such as steroids,
anticonvulsants, chemotherapeutic agents, and antiparkinsonian medications may also induce psychotic
symptoms. Toxic substances such as carbon monoxide
have also been reported to cause substance-induced
psychotic disorder.
Shared psychotic disorder
Shared psychotic disorder, also known as folie à
deux or psychosis by association, is a relatively rare
delusional disorder involving two (or more) people
with close emotional ties. In the West, shared psychosis most commonly develops between two sisters or
between husband and wife, while in Japan the most
common form involves a parent and a son or daughter. Shared psychosis occasionally involves an entire
nuclear family.
Psychosis is characterized by the following
symptoms:


Delusions. Those delusions that occur in schizophrenia and its related forms are typically bizarre (i.e.,
they could not occur in real life). Delusions occurring
in delusional disorder are more plausible, but still
patently untrue. In some cases, delusions may be
accompanied by feelings of paranoia.
3089

Psychosis

disorder in which it presents; psychosis can also be
caused by purely social factors, with no biological
component.

Psychosis



Hallucinations. Psychotic patients see, hear, smell,
taste, or feel things that aren’t there. Schizophrenic
hallucinations are typically auditory or, less commonly, visual; but psychotic hallucinations can
involve any of the five senses.



Disorganized speech. Psychotic patients, especially
those with schizophrenia, often ramble on in incoherent, nonsensical speech patterns.



Disorganized or catatonic behavior. The catatonic
patient reacts inappropriately to his/her environment by either remaining rigid and immobile or by
engaging in excessive motor activity. Disorganized
behavior is behavior or activity that is inappropriate
for the situation, or unpredictable.

Diagnosis
Patients with psychotic symptoms should
undergo a thorough physical examination and history
to rule out such possible organic causes as seizures,
delirium, or alcohol withdrawal, and such other psychiatric conditions as dissociation or panic attacks. If
a psychiatric cause such as schizophrenia is suspected,
a mental health professional will typically conduct an
interview with the patient and administer one of several clinical inventories, or tests, to evaluate mental
status. This assessment takes place in either an outpatient or hospital setting.
Psychotic symptoms and behaviors are considered
psychiatric emergencies, and persons showing signs of
psychosis are frequently taken by family, friends, or
the police to a hospital emergency room. A person
diagnosed as psychotic can be legally hospitalized
against his or her will, particularly if he or she is
violent, threatening to commit suicide, or threatening
to harm another person. A psychotic person may also
be hospitalized if he or she has become malnourished
or ill as a result of failure to feed, dress appropriately
for the climate, or otherwise take care of him- or
herself.

well as using
psychotherapy.

antipsychotic

medications

and

Antipsychotic medication such as thioridazine
(Mellaril), haloperidol (Haldol), chlorpromazine
(Thorazine), clozapine (Clozaril), sertindole (Serlect),
olanzapine (Zyprexa), or risperidone (Risperdal) is
usually prescribed to bring psychotic symptoms
under control and into remission. Possible side effects
of antipsychotics include dry mouth, drowsiness, muscle stiffness, and tardive dyskinesia (involuntary movements of the body). Agranulocytosis, a potentially
serious but reversible health condition in which the
white blood cells that fight infection in the body are
destroyed, is a possible side effect of clozapine.
Patients treated with this drug should undergo weekly
blood tests to monitor white blood cell counts for the
first six months, then every two weeks.
After an acute psychotic episode has subsided,
antipsychotic drug maintenance treatment is typically
employed and psychosocial therapy and living and
vocational skills training may be attempted.

Prognosis
Prognosis for brief psychotic disorder is quite
good; for schizophrenia, less so. Generally, the longer
and more severe a psychotic episode, the poorer the
prognosis is for the patient. Early diagnosis and treatment are critical to improving outcomes for the patient
across all psychotic disorders.
Approximately 10% of America’s permanently
disabled population is comprised of schizophrenic individuals. The mortality rate of schizophrenic individuals
is also high—approximately 10% of schizophrenics
commit suicide, and 20% attempt it. However, early
diagnosis and long-term follow up care can improve
the outlook for these patients considerably. Roughly
60% of patients with schizophrenia will show substantial improvement with appropriate treatment.
Resources

Treatment
Psychosis that is symptomatic of schizophrenia or
another psychiatric disorder should be treated by a
psychologist and/or psychiatrist. An appropriate
course of medication and/or psychosocial therapy is
employed to treat the underlying primary disorder.
If the patient is considered to be at risk for harming
himself or others, inpatient treatment is usually
recommended.
Treatment of shared psychotic disorder involves
separating the affected persons from one another as
3090

BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders.4th ed., revised.
Washington, D.C.: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychiatric Emergencies.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Schizophrenia and Related Disorders.’’ In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
GALE ENCYCLOPEDIA OF MEDICINE

Brief psychotic disorder—An acute, short-term episode of psychosis lasting no longer than one month.
This disorder may occur in response to a stressful
event.
Delirium—An acute but temporary disturbance of
consciousness marked by confusion, difficulty paying attention, delusions, hallucinations, or restlessness. Delirium may be caused by drug intoxication,
high fever related to infection, head trauma, brain
tumors, kidney or liver failure, or various metabolic
disturbances.
Delusional disorder—Individuals with delusional
disorder suffer from long-term, complex delusions
that fall into one of six categories: persecutory,
grandiose, jealousy, erotomanic, somatic, or mixed.
Delusions—An unshakable belief in something
untrue which cannot be explained by religious or
cultural factors. These irrational beliefs defy normal
reasoning and remain firm even when overwhelming proof is presented to refute them.
Hallucinations—False or distorted sensory experiences that appear to be real perceptions to the person
experiencing them.
Paranoia—An unfounded or exaggerated distrust of
others, sometimes reaching delusional proportions.

PERIODICALS

Addington, A. M., M. Gornick, A. L. Sporn, et al.
‘‘Polymorphisms in the 13q33.2 Gene G72/G30 Are
Associated with Childhood-Onset Schizophrenia and
Psychosis Not Otherwise Specified.’’ Biological
Psychiatry 55 (May 15, 2004): 976–980.
Hutchinson, G., and C. Haasen. ‘‘Migration and
Schizophrenia: The Challenges for European
Psychiatry and Implications for the Future.’’ Social
Psychiatry and Psychiatric Epidemiology 39 (May
2004): 350–357.
Sharon, Idan, MD, and Roni Sharon. ‘‘Shared Psychotic
Disorder.’’ eMedicine June 4, 2004. <http://
www.emedicine.com/med/topic3352.htm>.
Sim, M. G., E. Khong, and G. Hulse. ‘‘Cannabis and
Psychosis.’’ Australian Family Physician 33 (April
2004): 229–232.
Tolmac, J., and M. Hodes. ‘‘Ethnic Variation among
Adolescent Psychiatric In-Patients with Psychotic
Disorders.’’ British Journal of Psychiatry 184 (May
2004): 428–431.
GALE ENCYCLOPEDIA OF MEDICINE

Porphyria—A disease of the metabolism characterized by skin lesions, urine problems, neurologic disorders, and/or abdominal pain.
Schizoaffective disorder—Schizophrenic symptoms
occurring concurrently with a major depressive and/
or manic episode.
Schizophrenia—A debilitating mental illness characterized by delusions, hallucinations, disorganized
speech and behavior, and inappropriate or flattened
affect (a lack of emotions) that seriously hampers the
afflicted individual’s social and occupational functioning. Approximately 2 million Americans suffer
from schizophrenia.
Schizophreniform disorder—A short-term variation
of schizophrenia that has a total duration of one to
six months.
Shared psychotic disorder—Also known as folie à
deux, shared psychotic disorder is an uncommon
disorder in which the same delusion is shared by
two or more individuals.
Tardive dyskinesia— Involuntary movements of the
face and/or body which are a side effect of the longterm use of some older antipsychotic (neuroleptic)
drugs. Tardive dyskinesia affects 15-20% of patients
on long-term neuroleptic treatment.

Verdoux, H., and M. Tournier. ‘‘Cannabis Use and Risk of
Psychosis: An Etiological Link?’’ Epidemiologia e psichiatria sociale 13 (April-June 2004): 113–119.
Williams, N. M., and M. J. Owen. ‘‘Genetic Abnormalities
of Chromosome 22 and the Development of
Psychosis.’’ Current Psychiatry Reports 6 (June 2004):
176–182.
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<http://www.apa.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513. <http://
www.nimh.nih.gov>.
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Psychosis

KEY TERMS

Psychosocial disorders

OTHER



Somatoform disorders. Somatoform disorders
involve clinically significant physical symptoms that
cannot be explained by a medical condition (e.g.,
somatization disorder, conversion disorder, pain disorder, hypochondriasis, and body dysmorphic
disorder).



Factitious disorders. Disorders in which an individual creates and complains of symptoms of a nonexistent illness in order to assume the role of a patient
(or sick role).



Sexual and gender identity disorders. Disorders of
sexual desire, arousal, and performance. It should be
noted that the categorization of gender identity disorder as a mental illness has been a point of some
contention among mental health professionals.



Eating disorders. Anorexia and bulimia nervosa.



Adjustment disorders. Adjustment disorders involve
an excessive emotional or behavioral reaction to a
stressful event.



Personality disorders. Maladjustments of personality, including paranoid, schizoid, schizotypal, antisocial, borderline, histrionic, narcissistic, avoidant,
dependent, and obsessive-compulsive personality
disorder (not to be confused with the anxiety disorder OCD).



Disorders usually first diagnosed in infancy childhood, or adolescence. Some learning and developmental disorders (i.e., ADHD) may be partially
psychosocial in nature.

The Schizophrenia Page. <http://
www.schizophrenia.com>.

Paula Anne Ford-Martin
Rebecca Frey, PhD

Psychosocial disorders
Definition
A psychosocial disorder is a mental illness caused
or influenced by life experiences, as well as maladjusted cognitive and behavioral processes.

Description
The term psychosocial refers to the psychological
and social factors that influence mental health. Social
influences such as peer pressure, parental support,
cultural and religious background, socioeconomic status, and interpersonal relationships all help to shape
personality and influence psychological makeup.
Individuals with psychosocial disorders frequently
have difficulty functioning in social situations and
may have problems effectively communicating with
others.
In the American Psychiatric Association it distinguishes 16 different subtypes (or categories) of mental
illness. Although psychosocial variables arguably
have some degree of influence on all subtypes of mental illness, the major categories of mental disorders
thought to involve significant psychosocial factors
include:


Substance-related disorders. Disorders related to
alcohol and drug use, abuse, dependence, and
withdrawal.



Schizophrenia and other psychotic disorders. These
include the schizoid disorders (schizophrenia, schizophreniform, and schizoaffective disorder), delusional
disorder, and psychotic disorders.



Mood disorders. Affective disorders such as depression (major, dysthymic) and bipolar disorders.



Anxiety disorders. Disorders in which a certain situation or place triggers excessive fear and/or anxiety
symptoms (i.e., dizziness, racing heart), such as panic
disorder, agoraphobia, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, and
generalized anxiety disorders.

3092

Causes and symptoms
It is important to note that the causes of mental
illness are diverse and not completely understood. The
majority of psychological disorders are thought to be
caused by a complex combination of biological,
genetic (hereditary), familial, and social factors or
biopsychosocial influences. In addition, the role that
each of these play can differ from person to person, so
that a disorder such as depression that is caused by
genetic factors in one person may be caused by a
traumatic life event in another.
The symptoms of psychosocial disorders vary
depending on the diagnosis in question. In addition
to disorder-specific symptoms, individuals with psychosocial dysfunction usually have difficulty functioning normally in social situations and may have trouble
forming and maintaining close interpersonal
relationships.

GALE ENCYCLOPEDIA OF MEDICINE

Patients with symptoms of psychosocial disorders or other mental illness should undergo a thorough physical examination and patient history to rule
out an organic cause for the illness (such as a neurological disorder). If no organic cause is suspected, a
psychologist or other mental healthcare professional
will meet with the patient to conduct an interview and
take a detailed social and medical history. If the
patient is a minor, interviews with a parent or guardian may also be part of the diagnostic process. The
physician may also administer one or more psychological tests (also called clinical inventories, scales, or
assessments).

Treatment
Counseling is typically a front-line treatment for
psychosocial disorders. A number of counseling or
talk therapy approaches exist, including psychotherapy, cognitive therapy, behavioral therapy, and group
therapy. Therapy or counseling may be administered
by social workers, nurses, licensed counselors and
therapists, psychologists, or psychiatrists.
Psychoactive medication may also be prescribed
for symptom relief in patients with mental disorders
considered psychosocial in nature. For disorders such
as major depression or bipolar disorder, which may
have psychosocial aspects but also have known
organic causes, drug therapy is a primary treatment
approach. In cases such as personality disorder that
are thought to not have biological roots, psychoactive
medications are usually considered a secondary, or
companion treatment to psychotherapy.
Many individuals are successful in treating psychosocial disorders through regular attendance in selfhelp groups or 12-step programs such as Alcoholics
Anonymous. This approach, which allows individuals
to seek advice and counsel from others in similar
circumstances, can be extremely effective.
In some cases, treating mental illness requires
hospitalization of the patient. This hospitalization,
also known as inpatient treatment, is usually
employed in situations where a controlled therapeutic
environment is critical for the patient’s recovery (e.g.,
rehabilitation treatment for alcoholism or other drug
addictions), or when there is a risk that the patient may
harm himself (suicide) or others. It may also be necessary when the patient’s physical health has deteriorated to a point where life-sustaining treatment is
necessary, such as with severe malnutrition associated
with anorexia nervosa.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Affective disorder—An emotional disorder involving abnormal highs and/or lows in mood.
Bipolar disorder—An affective mental illness that
causes radical emotional changes and mood
swings, from manic highs to depressive lows. The
majority of bipolar individuals experience alternating episodes of mania and depression.
Bulimia—An eating disorder characterized by
binge eating and inappropriate compensatory
behavior such as vomiting, misusing laxatives, or
excessive exercise.
Cognitive processes—Thought processes (i.e., reasoning, perception, judgment, memory).
Learning disorders—Academic difficulties experienced by children and adults of average to aboveaverage intelligence that involve reading, writing,
and/or mathematics, and which significantly interfere with academic achievement or daily living.
Schizophrenia—A debilitating mental illness characterized by delusions, hallucinations, disorganized speech and behavior, and flattened affect
(i.e., a lack of emotions) that seriously hampers
normal functioning.

Alternative treatment
Therapeutic approaches such as art therapy that
encourage self-discovery and empowerment may be
useful in treating psychosocial disorders. Art therapy,
the use of the creative process to express and understand emotion, encompasses a broad range of humanistic disciplines, including visual arts, dance, drama,
music, film, writing, literature, and other artistic genres. This use of the creative process is believed to
provide the patient/artist with a means to gain insight
to emotions and thoughts they might otherwise have
difficulty expressing. After the artwork is created, the
patient/artist continues the therapeutic journey by
interpreting its meaning under the guidance of a
trained therapist.

Prognosis
According to the National Institute of Mental
Health, more than 90% of Americans who commit
suicide have a diagnosable mental disorder, so swift
and appropriate treatment is important. Because of
the diversity of types of mental disorders influenced
3093

Psychosocial disorders

Diagnosis

Psychosurgery

by psychosocial factors, and the complexity of diagnosis and treatment, the prognosis for psychosocial
disorders is highly variable. In some cases, they can
be effectively managed with therapy and/or medication. In others, mental illness can cause long-term
disability.

Prevention
Patient education (i.e., therapy or self-help
groups) can encourage patients to take an active part
in their treatment program and to recognize symptoms
of a relapse of their condition. In addition, educating
friends and family members on the nature of the psychosocial disorder can assist them in knowing how
and when to provide support to the patient.
Resources

brain and its purpose is to alleviate mental illness and
chronic pain symptoms. The bilateral cingulotomy, a
modern psychosurgical technique which has replaced
the lobotomy, is performed to alleviate mental disorders such as major depression, bipolar disorder, or
obsessive-compulsive disorder (OCD), which have not
responded to psychotherapy, behavioral therapy, electroshock, or pharmacologic treatment. Bilateral cingulotomies are also performed to treat chronic pain in
cancer patients.

Precautions
Psychosurgery should be considered only after all
other non-surgical psychiatric therapies have been
fully explored. Much is still unknown about the biology of the brain and how psychosurgery affects brain
function.

PERIODICALS

Epperly, Ted D., and Kevin E. Moore. ‘‘Health Issues in
Men: Part II. Common Psychosocial Disorders.’’
American Family Physician 62 (July 2000): 117-24.
ORGANIZATIONS

National Institute of Mental Health. 6001 Executive
Boulevard, Rm. 8184, MSC 9663, Bethesda, MD
20892-9663. (301) 443-4513.
OTHER

Satcher, David. Mental Health: A Report of the Surgeon
General. Washington, DC: Government Printing
Office, 1999.

Paula Anne Ford-Martin

Psychosurgery
Definition
Psychosurgery involves severing or otherwise disabling areas of the brain to treat a personality disorder, behavior disorder, or other mental illness.
Modern psychosurgical techniques target the pathways between the limbic system (the portion of the
brain on the inner edge of the cerebral cortex) that is
believed to regulate emotions, and the frontal cortex,
where thought processes are seated.

Description
Psychosurgery, and lobotomy in particular,
reached the height of use just after World War II.
Between 1946 and 1949, the use of the lobotomy grew
from 500 to 5,000 annual procedures in the United
States. At that time, the procedure was viewed as a
possible solution to the overcrowded and understaffed
conditions in state-run mental hospitals and asylums.
Known as prefrontal or transorbital lobotomy,
depending on the surgical technique used and area of
the brain targeted, these early operations were performed with surgical knives, electrodes, suction, or ice
picks, to cut or sweep out portions of the frontal lobe.
Today’s psychosurgical techniques are much
more refined. Instead of going in ‘‘blind’’ to remove
large sections on the frontal lobe, as in these early
operations, neurosurgeons use a computer-based process called stereotactic magnetic resonance imaging to
guide a small electrode to the limbic system (brain
structures involved in autonomic or automatic body
functions and some emotion and behavior). There an
electrical current burns in a small lesion [usually 0.5
in (1.3 cm) in size]. In a bilateral cingulotomy, the
cingulate gyrus, a small section of brain that connects
the limbic region of the brain with the frontal lobes,
is targeted. Another surgical technique uses a noninvasive tool known as a gamma knife to focus
beams of radiation at the brain. A lesion forms at the
spot where the beams converge in the brain.

Purpose
Lobotomy is a psychosurgical procedure involving selective destruction of connective nerve fibers
or tissue. It is performed on the frontal lobe of the
3094

Preparation
Candidates for cingulotomies or other forms of
psychosurgery undergo a rigorous screening process
GALE ENCYCLOPEDIA OF MEDICINE

Gamma knife—A surgical tool that focuses beams
of radiation at the head, which converge in the brain
to form a lesion.
Lesion—Any discontinuity of tissue. Often a cut or
wound.
Limbic system—A portion of the brain on the inner
edge of the cerebral cortex that is thought to regulate emotions.
Psychosurgery—Brain surgery performed to alleviate chronic psychological conditions such as obsessive-compulsive disorder (OCD), depression, and
bipolar disorder.
Stereotactic technique—A technique used by neurosurgeons to pinpoint locations within the brain. It
employs computer imaging to create an external
frame of reference.

to ensure that all possible non-surgical psychiatric
treatment options have been explored. Psychosurgery
is only performed with the patient’s informed consent.

Aftercare
Ongoing behavioral and medication therapy is
often required in OCD patients who undergo cingulotomy. All psychosurgery patients should remain
under a psychiatrist’s care for follow-up evaluations
and treatment.

Risks
As with any type of brain surgery, psychosurgery
carries the risk of permanent brain damage, though
the advent of non-invasive neurosurgical techniques,
such as the gamma knife, has reduced the risk of brain
damage significantly.

Normal results
In a 1996 study at Massachusetts General
Hospital, over one-third of patients undergoing cingulotomy demonstrated significant improvements after
the surgery. And, in contrast to the bizarre behavior
and personality changes reported with lobotomy
patients in the 1940s and 1950s, modern psychosurgery patients have demonstrated little post-surgical
losses of memory or other high level thought
processes.
GALE ENCYCLOPEDIA OF MEDICINE

Ptosis

Resources

KEY TERMS

ORGANIZATIONS

Massachusetts General Hospital. Functional and
Stereotactic Neurosurgery Cingulotomy Unit. Fruit St.,
Boston, MA 02114. (617) 726-2000. <http://neurosurgery.mgh.harvard.edu/cingulot.htm>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA
22201-3042. (800) 950-6264. <http://www.nami.org>.
National OCD Headquarters. P.O. Box 70, Milford, CT
06460. (203) 878-5669.

Paula Anne Ford-Martin

Psyllium preparations see Laxatives
PT see Prothrombin time
Pterygium see Pinguecula and pterygium
Ptomaine poisoning see Food poisoning

Ptosis
Definition
Ptosis is the term used for a drooping upper eyelid.
Ptosis, also called blepharoptosis, can affect one or
both eyes.

Description
The eyelids serve to protect and lubricate the outer
eye. The upper eyelid is lifted by a muscle called the
levator muscle. Inside the back part of the lid is a tarsal
plate which adds rigidity to the lid. The levator muscle
is attached to the tarsal plate by a flat tendon called the
levator aponeurosis. When the muscle cannot lift the
eyelid or lifts it only partially, the person is said to have
a ptosis.
There are two types of ptosis, acquired and
congenital. Acquired ptosis is more common.
Congenital ptosis is present at birth. Both congenital and acquired ptosis can be, but are not necessarily, hereditary.

Causes and symptoms
Ptosis may occur because the levator muscle’s
attachment to the lid is weakening with age.
Acquired ptosis can also be caused by a number of
different things, such as disease that impairs the
nerves, diabetes, injury, tumors, inflammation, or
3095

Ptosis

KEY TERMS
Congenital—A condition existing at birth.
Hereditary—A condition passed from parent to
child. In other words, a genetic condition.

any surgery, there are risks, and they should be discussed with the surgeon.

A close-up view of a drooping upper eyelid (ptosis) on an
elderly woman’s face. Ptosis is normally due to a weakness of
the levator muscle of the upper eyelid or to interference with
the nerve supply to the muscle. (Photograph by Dr. P. Marazzi,
Photo Researchers, Inc. Reproduced by permission.)

aneurysms. Congenital ptosis may be caused by a
problem with nerve innervation or a weak muscle.
Drooping eyelids may also be the result of diseases
such as myotonic dystrophy or myasthenia gravis.
The primary symptom of ptosis is a drooping eyelid. Adults will notice a loss of visual field because the
upper portion of the eye is covered. Children who are
born with a ptosis usually tilt their head back in an
effort to see under the obstruction. Some people raise
their eyebrows in order to lift the lid slightly and therefore may appear to be frowning.

Diagnosis
Diagnosis of ptosis is usually made by observing
the drooping eyelid. Finding the cause of the condition
will require testing for any of the illnesses or injuries
known to have this effect. Some possible tests include
x rays and blood tests.

Treatment
Ptosis is usually treated surgically. Surgery can
generally be done on an outpatient basis under local
anesthetic. For minor drooping, a small amount of the
eyelid tissue can be removed. For more pronounced
ptosis the approach is to surgically shorten the levator
muscle or connect the lid to the muscles of the eyebrow. Or, the aponeurosis can be reattached to the
tarsal plate if it has separated. Correcting the ptosis is
usually done only after determining the cause of the
condition. For example, myasthenia gravis must be
ruled out before performing any surgery. As with
3096

Children with ptosis need not have surgery immediately, however their vision must be checked periodically to prevent lazy eye (amblyopia).
‘‘Ptosis crutches’’ are also available. These can be
attached to the frame of eyeglasses to hold up the
eyelid. These devices are uncomfortable and usually
not well tolerated.

Prognosis
After diagnosing the cause of a drooping eyelid,
then correcting the condition, most people have no
further problems related to the ptosis. The correction, however, may still not make the eyes symmetrical. Patients should have reasonable expectations and
discuss the outcome with their doctor prior to
surgery.

Prevention
Ptosis cannot be prevented.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://www.amaassn.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
U.S. Department of Health and Human Services. 200
Independence Ave., SW, Washington, DC 20201, (202)
619-0257

Dorothy Elinor Stonely

PTSD see Post-traumatic stress disorder
PTT see Partial thromboplastin time
GALE ENCYCLOPEDIA OF MEDICINE

Excess hormone stimulation is the cause for precocious puberty. It can come from the brain in the form
of gonadotrophins or from the gonads and adrenals.
Overproduction may be caused by functioning
tumors or simple overactivity. Brain overproduction
can also be the result of brain infections or injury.



Likewise, delayed puberty is due to insufficient hormone. If the pituitary output is inadequate, so will be
the output from the gonads and adrenals. On the
other hand, a normal pituitary will overproduce if it
senses there are not enough hormones in the
circulation.



There are several congenital disorders (polyglandular deficiency syndromes) that include failure of hormone output. These children do not experience
normal puberty, but it may be induced by giving
them the proper hormones at the proper time.



Finally, there are in females abnormalities in hormone production that produce male characteristics–so called virilizing syndromes. Should one of
these appear during adolescence, it will disturb the
normal progress of puberty. Notice that virilizing
requires abnormal hormones in the female, while
feminizing results from absent hormones in the
male. Each embryo starts out life as female. Male
hormones transform it if they are present.

Puberty
Definition
Puberty is the period of human development during which physical growth and sexual maturation
occurs.

Description
Beginning as early as age eight in girls–and two
years later, on average, in boys–the hypothalamus
(part of the brain) signals hormonal change that stimulates the pituitary. In turn, the pituitary releases its
own hormones called gonadotrophins that stimulate
the gonads and adrenals. From these glands come a
flood of sex hormones–androgens and testosterone in
the male, estrogens and progestins in the female–that
regulate the growth and function of the sex organs. It
is interesting to note that the gonadotrophins are the
same for males and females, but the sex hormones they
induce are different.
In the United States, the first sign of puberty
occurs on average at age 11 in girls, with menstruation
and fertility following about two years later. Boys lag
behind by about two years. Puberty may not begin
until age 16 in boys and continue in a desultory fashion
on past age 20. In contrast to puberty, adolescence is
more of a social/cultural term referring to the interval
between childhood and adulthood.

Diagnosis
Puberty has been divided into five Sexual Maturity
Rating (SMR) stages by two doctors, W. Marshall and
J. M. Tanner. These ratings are often referred to as
Tanner Stages 1–5. Staging is based on pubic hair
growth, on male genital development, and female
breast development. Staging helps determine whether
development is normal for a given age. Both sexes also
grow axillary (arm pit) hair and pimples. Males develop
muscle mass, a deeper voice, and facial hair. Females
redistribute body fat. Along with the maturing of the
sex organs, there is a pronounced growth spurt averaging 3–4 in (8–10 cm) and culminating in full adult
stature. Puberty can be precocious (early) or delayed. It
all depends upon the sex hormones.
Puberty falling outside the age limits considered
normal for any given population should prompt a
search for the cause. As health and nutrition have
improved over the past few generations, there has
been a gradual decrease in the average age for the
normal onset of puberty.
GALE ENCYCLOPEDIA OF MEDICINE

Delayed or precocious puberty requires measurement of the several hormones involved to determine
which are lacking or which are in excess. There are
blood tests for each one. If a tumor is suspected,
imaging of the suspect organ needs to be done with x
rays, computed tomography scans (CT scans), or magnetic resonance imaging (MRI).

Treatment
Puberty is a period of great stress, both physically
and emotionally. The psychological changes and challenges of puberty are made infinitely greater if its
timing is off.
In precocious puberty, the offending gland or
tumor may require surgical attention, although there
are several drugs now that counteract hormone
effects. If delayed, puberty can be stimulated with the
correct hormones. Treatment should not be delayed
because necessary bone growth is also affected.

Prognosis
Properly administered hormones can restore the
normal growth pattern.
3097

Puberty



Puerperal infection

Description

KEY TERMS
Adrenals—Glands on top of the kidneys that produce four different types of hormones.
Computed tomography scan (CT)—A method of
creating images of internal organs using x rays.
Embryo—The life in the womb during the first two
months.
Hormone—A chemical produced in one place that
has an effect somewhere else in the body.
Hypothalamus—Part of the brain located deep in
the center of the skull and just above the pituitary.
Gonads—Glands that make sex hormones and
reproductive cells–testes in the male, ovaries in
the female.
Magnetic resonance imaging (MRI)—A method of
creating images of internal organs. Magnetic resonance imaging (MRI) uses magnet fields and radiofrequency signals.
Pituitary—The ‘‘master gland’’ of the body, controlling many of the others by releasing stimulating
hormones.
Syndrome—A collection of abnormalities that
occur often enough to suggest they have a common
cause.

Resources
BOOKS

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Pubic lice see Lice infestation

Puerperal infection
Definition
The term puerperal infection refers to a bacterial
infection following childbirth. The infection may also
be referred to as puerperal or postpartum fever. The
genital tract, particularly the uterus, is the most commonly infected site. In some cases infection can spread
to other points in the body. Widespread infection, or
sepsis, is a rare, but potentially fatal complication.
3098

Puerperal infection affects an estimated 1–8% of
new mothers in the United States. Given modern medical treatment and antibiotics, it very rarely advances
to the point of threatening a woman’s life. An estimated 2–4% of new mothers who deliver vaginally
suffer some form of puerperal infection, but for cesarean sections, the figure is five-10 times that high.
Deaths related to puerperal infection are very rare
in the industrialized world. It is estimated three in
100,000 births result in maternal death due to infection. However, the death rate in developing nations
may be 100 times higher.
Postpartum fever may arise from several causes,
not necessarily infection. If the fever is related to infection, it often results from endometritis, an inflammation of the uterus. Urinary tract, breast, and wound
infections are also possible, as well as septic thrombophlebitis, a blood clot-associated inflammation of
veins. A woman’s susceptibility to developing an infection is related to such factors as cesarean section,
extended labor, obesity, anemia, and poor prenatal
nutrition.

Causes and symptoms
The primary symptom of puerperal infection is a
fever at any point between birth and 10 days postpartum. A temperature of 100.48F (388C) on any two days
during this period, or a fever of 101.68F (38.6 8C) in
the first 24 hours postpartum, is cause for suspicion.
An assortment of bacterial species may cause puerperal infection. Many of these bacteria are normally
found in the mother’s genital tract, but other bacteria
may be introduced from the woman’s intestine and
skin or from a healthcare provider.
The associated symptoms depend on the site and
nature of the infection. The most typical site of infection is the genital tract. Endometritis, which affects the
uterus, is the most prominent of these infections.
Endometritis is much more common if a small part
of the placenta has been retained in the uterus.
Typically, several species of bacteria are involved and
may act synergistically–that is, the bacteria’s negative
effects are multiplied rather than simply added
together. Synergistic action by the bacteria can result
in a stubborn infection such as an abscess. The major
symptoms of a genital tract infection include fever,
malaise, abdominal pain, uterine tenderness, and
abnormal vaginal discharge. If these symptoms do
not respond to antibiotic therapy, an abscess or
blood clot may be suspected.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Fever is not an automatic indicator of puerperal
infection. A new mother may have a fever owing to
prior illness or an illness unconnected to childbirth.
However, any fever within 10 days postpartum is aggressively investigated. Physical symptoms such as pain,
malaise, loss of appetite, and others point to infection.
Many doctors initiate antibiotic therapy early in
the fever period to stop an infection before it advances.
A pelvic examination is done and samples are taken
from the genital tract to identify the bacteria involved
in the infection. The pelvic examination can reveal the
extent of infection and possibly the cause. Blood samples may also be taken for blood counts and to test for
the presence of infectious bacteria. A urinalysis may
also be ordered, especially if the symptoms are indicative of a urinary tract infection.
If the fever and other symptoms resist antibiotic
therapy, an ultrasound examination or computed
tomography scan (CT scan) is done to locate potential
abscesses or blood clots in the pelvic region. Magnetic
resonance imaging (MRI) may be useful as well, in
addition to a heparin challenge test if blood clots are
suspected. If a lung infection is suspected, a chest x ray
may also be ordered.

Treatment
Antibiotic therapy is the backbone of puerperal
infection treatment. Initial antibiotic therapy may
consist of clindamycin and gentamicin, which fight a
broad array of bacteria types. If the fever and other
symptoms do not respond to these antibiotics, a third,
such as ampicillin, is added. Other antibiotics may be
used depending on the identity of the infective bacteria
and the possibility of an allergic reaction to certain
antibiotics.
Antibiotics taken together are effective against a
wide range of bacteria, but may not be capable of
clearing up the infection alone, especially if an abscess
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Abscess—A pus-filled area with definite borders.
Blood clot—A dense mat formed by certain components of the blood stream to prevent blood loss.
Cesarean section—Incision through the abdomen
and uterus to facilitate delivery.
Computed tomography scan (CT scan)—Crosssectional x rays of the body are compiled to create
a three-dimensional image of the body’s internal
structures.
Episiotomy—Incision of the vulva (external female
genitalia) during vaginal delivery to prevent tissue
tearing.
Heparin—A blood component that controls the
amount of clotting. It can be used as a drug to
reduce blood clot formation.
Heparin challenge test—A medical test to evaluate
how readily the blood clots.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Postpartum—Referring to the time period following childbirth.
Prophylactic—Measures taken to prevent disease.
Sepsis—The presence of viable bacteria in the
blood or body tissues.
Septic—Referring to the presence of infection.
Thrombophlebitis—An inflammation of veins
accompanied by the formation of blood clots.
Ultrasound examination—A medical test in which
high frequency sound waves are directed at a particular internal area of the body. As the sound waves
are reflected by internal structures, a computer uses
the data to construct an image of the structures.
Warfarin—A drug that reduces the ability of the
blood to clot.

or blood clot is present. Heparin is combined with the
antibiotic therapy in order to break apart blood clots.
Heparin is used for five-seven days, and may be followed by warfarin for the following month. If the
infection is complicated, it may be necessary to surgically drain the infected site. Infected episiotomies can
be opened and allowed to drain, but abscesses and
blood clots may require surgery.
3099

Puerperal infection

Other causes of postpartum fever include urinary
tract infections, wound infections, septic thrombophlebitis, and mastitis. Mastitis, or breast infection, is indicated by fever, malaise, achy muscles, and reddened
skin on the affected breast. It is usually caused by a
clogged milk duct that becomes infected. Infections of
the urinary tract are indicated by fever, frequent and
painful urination, and back pain. An episiotomy and a
cesarean section carry the risk of a wound infection.
Such infections are suggested by a fever and pus-like
discharge, inflammation, and swelling at wound sites.

Pulmonary alveolar proteinosis

Prognosis
Antibiotic therapy and other treatment measures
are virtually always successful in curing puerperal
infections.

Prevention
Careful attention to antiseptic procedures during
childbirth is the basic underpinning of preventing
infection. With some procedures, such as cesarean
section, a doctor may administer prophylactic antibiotics as a preemptive strike against infectious
bacteria.
Resources
PERIODICALS

Hamadeh, Ghassan, Cindy Dedmon, and Paul D. Mozley.
‘‘Postpartum Fever.’’ American Family Physician 52,
no. 2 (August 1995): 531.

KEY TERMS
Alveoli—The small cavities, or air sacs, in the
lungs.
Bronchoscopy—A bronchoscopy is the examination of the bronchi, the primary divisions of the
trachea that penetrate the lung, through a tube
called a bronchoscope.
Clubbing—Clubbing is the rounding of the ends
and swelling of fingers found in people with lung
disease.
Remission—Lessening of severity, or abatement of
symptoms.
Transtracheal biopsy—A transtracheal biopsy is
the removal of a small piece of tissue from across
the trachea or windpipe for examination under a
microscope.

Julia Barrett
immune deficiency, or from exposure to silica, aluminum oxide, and a variety of dusts and fumes.

Pulmonary alveolar
proteinosis

Symptoms include mild shortness of breath associated with a nonproductive or minimally productive
cough, weight loss, and fatigue. Acute symptoms such
as fever or progressive shortness of breath suggest a
complicating infection.

Definition
Pulmonary alveolar proteinosis (PAP) is a rare
disease of the lungs.

Description

Diagnosis
Physical examination may reveal clubbing of the
fingers or a bluish coloration of the skin as a result of
decreased oxygen.

In this disease, also called alveolar proteinosis or
phospholipidosis, gas exchange in the lungs is progressively impaired by the accumulation of phospholipids,
compounds widely found in other living cells of the
body. The alveoli are filled with this substance that
renders them less effective in protecting the lung. This
may explain why infections are often associated with
the disease.

A chest x ray may show alveolar disease. An arterial blood gas reveals low oxygen levels in the blood.
Bronchoscopy with transtracheal biopsy shows alveolar proteinosis. Specific diagnosis requires a lung
biopsy.

Pulmonary alveolar proteinosis most commonly
affects people ages 20–50, although it has been
reported in children and the elderly. The incidence is
5 out of every 1 million people. The disease is more
common among males.

Treatment consists of periodic whole-lung lavage,
a washing out of the phospholipids from the lung with
a special tube placed in the trachea. This is performed
under general anesthesia.

Treatment

Prognosis
Causes and symptoms
The cause of this disease is unknown. In some
people, however, it appears to result from infection,
3100

In some, spontaneous remission occurs, while in
others progressive respiratory failure develops.
Disability from respiratory insufficiency is common,
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
There is no known prevention for this very rare
disorder.
Resources
ORGANIZATIONS

American Association for Respiratory Care. 11030 Ables
Lane, Dallas, Texas 75229. (972) 243-2272. <http://
www.aarc.org>.
American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.

performed at the bedside of a patient in the intensive
care unit. A catheter is threaded through a vein in the
arm, thigh, chest, or neck until it passes through the
right side of the heart. This procedure takes about 30
minutes. Local anesthesia is given to reduce
discomfort.
Once the catheter is in place, the doctor briefly
inflates a tiny balloon at its end. This temporarily
blocks the blood flow and allows the doctor to make
a pressure measurement in the pulmonary artery system. Pressure measurements are usually recorded for
the next 48–72 hours in different parts of the heart.
During this time, the patient must stay in bed so the
catheter stays in place. Once the pressure measurements are no longer needed, the catheter is removed.

Lorraine Steefel, RN

Pulmonary artery
catheterization

Preparation
Before and during the test, the patient will be
connected to an electrocardiograph, which makes a
recording of the electrical stimuli that cause the heart
to contract. The insertion site is sterilized and prepared. The catheter is often sutured to the skin to
prevent dislodgment.

Definition
Pulmonary artery catheterization is a diagnostic
procedure in which a small catheter is inserted through
a neck, arm, chest, or thigh vein and maneuvered into
the right side of the heart, in order to measure pressures at different spots in the heart.

Purpose
Pulmonary artery catheterization is performed to:

Aftercare
The patient is observed for any sign of infection or
complications from the procedure.

Risks
Pulmonary artery catheterization is not without
risks. Possible complications from the procedure
include:



evaluate heart failure



infection at the site where the catheter was inserted



monitor therapy after a heart attack



pulmonary artery perforation



check the fluid balance of a patient with serious
burns, kidney disease, or after heart surgery



blood clots in the lungs

check the effect of medications on the heart



irregular heartbeat



Normal results

Precautions
Pulmonary artery catheterization is a potentially
complicated and invasive procedure. The doctor must
decide if the value of the information obtained will
outweigh the risk of catheterization.

Normal pressures reflect a normally functioning
heart with no fluid accumulation. These normal pressure readings are:


right atrium: 1–6 mm of mercury (mm Hg)



right ventricle during contraction (systolic): 20–30
mm Hg



right ventricle at the end of relaxation (end diastolic):
less than 5 mm Hg

Description
Pulmonary artery catheterization, sometimes
called Swan-Ganz catheterization, is usually
GALE ENCYCLOPEDIA OF MEDICINE

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Pulmonary artery catheterization

but death rarely occurs. Repeated lavage may be
necessary. Lung transplant is a last resort option.

Pulmonary edema

KEY TERMS
Cardiac shunt—A defect in the wall of the heart
that allows blood from different chambers to mix.



left ventricle failure



mitral valve abnormalities



cardiac insufficiency



compression of the heart after hemorrhage

Resources


pulmonary artery during contraction (systolic):
20–30 mm Hg



pulmonary artery during relaxation (diastolic):
about 10 mm Hg



mean pulmonary artery: less than 20 mm Hg



pulmonary artery wedge pressure: 6–12 mm Hg



left atrium: about 10 mm Hg

‘‘Pulmonary Artery Catheterization.’’ In The Patient’s Guide
to Medical Tests, ed. Barry L. Zaret, et al., Boston:
Houghton Mifflin, 1997.

Tish Davidson, A.M.

Abnormal results
Abnormally high right atrium pressure can
indicate:

Pulmonary edema
Definition
Pulmonary edema is a condition in which fluid
accumulates in the lungs, usually because the heart’s
left ventricle does not pump adequately.



pulmonary disease



right side heart failure



fluid accumulation



compression of the heart after hemorrhage (cardiac
tamponade)



right heart valve abnormalities



pulmonary hypertension (high blood pressure)

Abnormally high right ventricle pressure may
indicate:


pulmonary hypertension (high blood pressure)



pulmonary valve abnormalities



right ventricle failure



defects in the wall between the right and left ventricle



congestive heart failure



serious heart inflammation

Abnormally high pulmonary artery pressure may
indicate:


diversion of blood from a left-to-right cardiac shunt



pulmonary artery hypertension



chronic obstructive
emphysema



blood clots in the lungs



fluid accumulation in the lungs



left ventricle failure

pulmonary

disease

or

Abnormally high pulmonary artery wedge pressure may indicate:
3102

BOOKS

Description
The build-up of fluid in the spaces outside the
blood vessels of the lungs is called pulmonary edema.
Pulmonary edema is a common complication of heart
disorders, and most cases of the condition are associated with heart failure. Pulmonary edema can be a
chronic condition, or it can develop suddenly and
quickly become life threatening. The life-threatening
type of pulmonary edema occurs when a large amount
of fluid suddenly shifts from the pulmonary blood
vessels into the lung, due to lung problems, heart
attack, trauma, or toxic chemicals. It can also be the
first sign of coronary heart disease.
In heart-related pulmonary edema, the heart’s
main chamber, the left ventricle, is weakened and
does not function properly. The ventricle does not
completely eject its contents, causing blood to back
up and cardiac output to drop. The body responds by
increasing blood pressure and fluid volume to compensate for the reduced cardiac output. This, in turn,
increases the force against which the ventricle must
expel blood. Blood backs up, forming a pool in the
pulmonary blood vessels. Fluid leaks into the spaces
between the tissues of the lungs and begins to accumulate. This process makes it more difficult for the lungs
to expand. It also impedes the exchange of air and
gases between the lungs and blood moving through
lung blood vessels.
GALE ENCYCLOPEDIA OF MEDICINE

Most cases of pulmonary edema are caused by
failure of the heart’s main chamber, the left ventricle.
It can be brought on by an acute heart attack, severe
ischemia, volume overload of the heart’s left ventricle,
and mitral stenosis. Non-heart-related pulmonary
edema is caused by lung problems like pneumonia, an
excess of intravenous fluids, some types of kidney disease, bad burns, liver disease, nutritional problems,
and Hodgkin’s disease. Non-heart-related pulmonary
edema can also be caused by other conditions where
the lungs do not drain properly, and conditions where
the respiratory veins are blocked.
Early symptoms of pulmonary edema include:


shortness of breath upon exertion



sudden respiratory distress after sleep



difficulty breathing, except when sitting upright



coughing

In cases of severe pulmonary edema, these symptoms will worsen to:


labored and rapid breathing



frothy, bloody fluid containing pus coughed from the
lungs (sputum)



a fast pulse and possibly serious disturbances in the
heart’s rhythm (atrial fibrillation, for example)



cold, clammy, sweaty, and bluish skin



a drop in blood pressure resulting in a thready pulse

Diagnosis
A doctor can usually diagnose pulmonary edema
based on the patient’s symptoms and a physical exam.
Patients with pulmonary edema will have a rapid
pulse, rapid breathing, abnormal breath and heart
sounds, and enlarged neck veins. A chest x ray is
often used to confirm the diagnosis. Arterial blood
gas testing may be done. Sometimes pulmonary artery
catheterization is performed to confirm that the
patient has pulmonary edema and not a disease with
similar symptoms (called adult respiratory distress syndrome or ‘‘noncardiogenic pulmonary edema’’).

Treatment
Pulmonary edema requires immediate emergency
treatment. Treatment includes: placing the patient in a
sitting position, oxygen, assisted or mechanical ventilation (in some cases), and drug therapy. The goal of
treatment is to reduce the amount of fluid in the lungs,
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Edema—Swelling caused by accumulation of fluid
in body tissues.
Ischemia—A condition in which the heart muscle
receives an insufficient supply of blood and slowly
starves.
Left ventricle—The large chamber on the lower left
side of the heart. The left ventricle sends blood to
the aorta and the rest of the body.
Mitral stenosis—Narrowing or constricting of the
mitral valve, which separates the left atrium from
the left ventricle.
Pulmonary—Referring to the lungs and respiratory
system.

improve gas exchange and heart function, and, where
possible, to correct the underlying disease.
To help the patient breathe better, he/she is placed in
a sitting position. High concentrations of oxygen are
administered. In cases where respiratory distress is
severe, a mechanical ventilator and a tube down the
throat (tracheal intubation) will be used to improve the
delivery of oxygen. Non-invasive pressure support ventilation is a new treatment for pulmonary edema in which
the patient breathes against a continuous flow of positive
airway pressure, delivered through a face or nasal mask.
Non-invasive pressure support ventilation decreases the
effort required to breath, enhances oxygen and carbon
dioxide exchange, and increases cardiac output.
Drug therapy could include morphine, nitroglycerin, diuretics, angiotensin-converting enzyme (ACE)
inhibitors, and vasodilators. Vasopressors are used for
cardiogenic shock. Morphine is very effective in reducing the patient’s anxiety, easing breathing, and
improving blood flow. Nitroglycerin reduces pulmonary blood flow and decreases the volume of fluid
entering the overloaded blood vessels. Diuretics, like
furosemide (Lasix), promote the elimination of fluids
through urination, helping to reduce pressure and
fluids in the blood vessels. ACE inhibitors reduce the
pressure against which the left ventricle must expel
blood. In patients who have severe hypertension, a
vasodilator such as nitroprusside sodium (Nipride)
may be used. For cardiogenic shock, an adrenergic
agent (like dopamine hydrochloride [Intropin], dobutamine hydrochloride [Dobutrex], or epinephrine) or a
bipyridine (like amrinone lactate [Inocor] or milrinone
lactate [Primacor]) are given.
3103

Pulmonary edema

Causes and symptoms

Pulmonary embolism

Prognosis
Most patients with pulmonary edema who seek
immediate treatment can be treated quickly and
effectively.

Prevention
Cardiogenic pulmonary edema can sometimes be
prevented by treating the underlying heart disease.
These treatments, can including maintaining a healthy
diet, taking appropriate medications correctly, and
avoiding excess alcohol and salt.
Resources
PERIODICALS

Sacchetti, Alfred D., and Russel H. Harris. ‘‘Acute
Cardiogenic Pulmonary Edema: What’s the Latest in
Emergency Treatment?’’ Postgraduate Medicine 103,
no. 2 (February 1998): 145-166.

Lori De Milto

Pulmonary embolism

also be comprised of fat, air, or tumor tissue. When
emboli block the main pulmonary artery, pulmonary
embolism can quickly become fatal.

Causes and symptoms
Pulmonary embolism is caused by emboli that
travel through the blood stream to the lungs and
block a pulmonary artery. When this occurs, circulation and oxygenation of blood is compromised. The
emboli are usually formed from blood clots but are
occasionally comprised of air, fat, or tumor tissue.
Risk factors include: prolonged bed rest, surgery,
childbirth, heart attack, stroke, congestive heart failure, cancer, obesity, a broken hip or leg, oral contraceptives, sickle cell anemia, congenital coagulation
disorders, chest trauma, certain congenital heart
defects, and old age.
Common symptoms of pulmonary embolism
include:


labored breathing, sometimes accompanied by chest
pain.



a rapid pulse.



a cough that produces bloody sputum.



a low fever.



fluid build-up in the lungs.

Definition
Pulmonary embolism is an obstruction of a blood
vessel in the lungs, usually due to a blood clot, which
blocks a coronary artery.

Description
Pulmonary embolism is a fairly common condition that can be fatal. According to the American
Heart Association, an estimated 600,000 Americans
develop pulmonary embolism annually; 60,000 die
from it. As many as 25,000 Americans are hospitalized
each year for pulmonary embolism, which is a relatively common complication in hospitalized patients.
Even without warning symptoms, pulmonary embolism can cause sudden death. Treatment is not always
successful.
Pulmonary embolism is difficult to diagnose. Less
than 10% of patients who die from pulmonary embolism were diagnosed with the condition. It occurs when
emboli block a pulmonary artery, usually due to a
blood clot that breaks off from a large vein and travels
to the lungs. More than 90% of cases of pulmonary
embolism are complications of deep vein thrombosis,
blood clots from the leg or pelvic veins. Emboli can
3104

Less common symptoms include:


coughing up a lot of blood



pain caused by movement



leg swelling



bluish skin



fainting



swollen neck veins
In some cases there are no symptoms.

Diagnosis
Pulmonary embolism can be diagnosed through
the patient’s history, a physical exam, and diagnostic
tests including chest x ray, lung scan, pulmonary
angiography, electrocardiography, arterial blood gas
measurements, and leg vein ultrasonography or
venography.
A chest x ray can be normal or show fluid or other
signs and rule out other diseases. The lung scan shows
poor flow of blood in areas beyond blocked arteries.
The patient inhales a small amount of radiopharmaceutical and pictures of airflow into the lungs are taken
with a gamma camera. Then a different
GALE ENCYCLOPEDIA OF MEDICINE

Deep vein thrombosis—A blood clot in the calf’s
deep vein. This frequently leads to pulmonary
embolism if untreated.
Emboli—Clots or other substances that travel
through the blood stream and get stuck in an artery,
blocking circulation.
Thrombosis—The development of a blood clot
inside a blood vessel.

An angiography of a pulmonary embolism. (Custom Medical
Stock Photo. Reproduced by permission.)

radiopharmaceutical is injected into an arm vein and
lung blood flow is scanned. A normal result essentially
rules out pulmonary embolism. A lung scan can be
performed in a hospital or an outpatient facility and
takes about 45 minutes.
Pulmonary angiography is the most reliable test
for diagnosing pulmonary embolism but it is not used
often, because it carries some risk and is expensive,
invasive, and not readily available in many hospitals.
Pulmonary angiography is a radiographic test which
involves injection of a pharmaceutical ‘‘contrast
agent’’ to show up the pulmonary arteries. A cinematic
camera records the blood flow through the lungs of the
patient, who lies on a table. Pulmonary angiography is
usually performed in a hospital’s radiology department and takes 30 minutes to one hour.
An electrocardiograph shows the heart’s electrical
activity and helps distinguish pulmonary embolism
from a heart attack. Electrodes covered with conducting jelly are placed on the patient’s chest, arms, and
legs. Impulses of the heart’s activity are traced on
paper. The test takes about 10 minutes and can be
performed in a physician’s office or hospital lab.
Arterial blood gas measurements can be helpful,
but they are rarely diagnostic for pulmonary embolism. Blood is taken from an artery instead of a vein,
usually in the wrist and it is analyzed for oxygen,
carbon dioxide and acid levels.
Venography is used to look for the most likely
source of pulmonary embolism, deep vein thrombosis.
It is very accurate, but it is not used often, because it is
painful, expensive, exposes the patient to a fairly high
dose of radiation, and can cause complications.
Venography identifies the location, extent, and degree
of attachment of the blood clots and enables the
GALE ENCYCLOPEDIA OF MEDICINE

condition of the deep leg veins to be assessed. A contrast solution is injected into a foot vein through a
catheter. The physician observes the movement of the
solution through the vein with a fluoroscope while a
series of x rays are taken. Venography takes between
30–45 minutes and can be done in a physician’s office, a
laboratory, or a hospital. Radionuclide venography, in
which a radioactive isotope is injected, is occasionally
used, especially if a patient has had reactions to contrast
solutions. Most commonly performed are ultrasound
and Doppler studies of leg veins.

Treatment
Patients with pulmonary embolism are hospitalized and generally treated with clot-dissolving and
clot-preventing drugs. Oxygen therapy is often needed
to maintain normal oxygen concentrations. For people who can’t take anticoagulants and in some other
cases, surgery may be needed to insert a device that
filters blood returning to the heart and lungs. The goal
of treatment is to maintain the patient’s cardiovascular and respiratory functions while the blockage
resolves, which takes 10–14 days, and to prevent the
formation of other emboli.
Thrombolytic therapy to dissolve blood clots is the
aggressive treatment for very severe pulmonary embolism. Streptokinase, urokinase, and recombinant tissue plasminogen activator (TPA) are thrombolytic
agents. Heparin is the injectable anticoagulant (clotpreventing) drug of choice for preventing formation of
blood clots. Warfarin, an oral anticoagulant, is usually
continued when the patient leaves the hospital and
doesn’t need heparin any longer.

Prognosis
About 10% of patients with pulmonary embolism
die suddenly within the first hour of onset of the
3105

Pulmonary embolism

KEY TERMS

Pulmonary fibrosis

condition. The outcome for all other patients is generally good; only 3% of patients who are properly
diagnosed and treated die. In cases of undiagnosed
pulmonary embolism, about 30% of patients die.

Prevention
Pulmonary embolism risk can be reduced in certain patients through judicious use of antithrombotic
drugs such as heparin, venous interruption, gradient
elastic stockings and/or intermittent pneumatic compression of the legs.
Resources

Causes and symptoms
The causes and risk factors vary with the underlying disease. They may include genetics, environmental factors, and infections.
The first symptom of pulmonary fibrosis is
usually shortness of breath—at first, during exercise,
but later also while resting. Patients may also have a
dry cough, a rapid heartbeat, or enlargement of the
fingertips and ends of the toes. Some people feel tired
or have a fever, weight loss, muscle or joint pains. In
late stages of the disease, the lack of oxygen in the
blood can give the skin and mucus membranes a blue
tinge known as cyanosis.

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300 or (800) 242-8721.
inquire@heart.org<http://www.americanheart.org>.

Lori De Milto

Pulmonary fibrosis
Definition
Pulmonary fibrosis is scarring in the lungs.

Description
Pulmonary fibrosis develops when the alveoli, tiny
air sacs that transfer oxygen to the blood, become
damaged and inflamed. The body tries to heal the
damage with scars, but these scars collapse the alveoli
and make the lungs less elastic. If the cycle of inflammation and scarring continues, the lungs become
increasingly unable to deliver oxygen to the blood.
Changes in the lungs can also increase the blood pressure in the pulmonary artery. This condition, called
pulmonary hypertension, makes the heart work harder
and it may fail.

Diagnosis
Pulmonary fibrosis is often referred to a lung
specialist. Several tests are usually needed to diagnose
this disease and determine its cause. They include a
physical examination, detailed history of the symptoms, chest x rays, lung function tests, and blood
tests, including a measurement of the amount of oxygen in the blood. Computed tomography (CT scan)
may give a more detailed picture of the lungs.
Bronchoscopy may be done to examine the air passages
and analyze the cells found deep in the lungs.
Lung biopsies are necessary to diagnose some
diseases. Lung biopsies can be done through a needle
inserted into the chest through the skin, during
bronchoscopy, or as a surgical procedure under general anesthesia.

Treatment
The treatment of pulmonary fibrosis depends on
the underlying cause. Many diseases are treated by
suppressing inflammation with corticosteroids.
Stronger immune suppressants such as cyclophosphamide (Cytoxan) or azathioprine (Imuran) may also be
tried. Some patients need supplemental oxygen. A
lung transplant may be an option for incurable diseases. Approximately 60–80% of patients live for at
least two years after the transplant.

Pulmonary fibrosis can result from many different
lung diseases including sarcoidosis, drug reactions,
autoimmune diseases, environmental allergies such
as Farmer’s lung, and exposure to toxic dusts and
gases.

There is no good treatment for idiopathic pulmonary fibrosis. Only 10–20% of patients with this
disease respond to corticosteroids.

Pulmonary fibrosis that develops without a
known cause is called idiopathic pulmonary fibrosis.
This disease is equally common in men and women. It
is usually diagnosed between the ages of 40 and 60.

Anxiety and fear can make breathing difficulties
worse. Some patients find that activities such as yoga,
prayer or meditation, music therapy, or biofeedback
help to relax them.

3106

Alternative treatment

GALE ENCYCLOPEDIA OF MEDICINE

Alveoli—Tiny air sacs in the lungs where oxygen and carbon dioxide are exchanged with the
blood.
Autoimmune disease—A disease that develops
when the immune system attacks normal cells or
organs.
Bronchoscopy Scan—The examination of the air
passages through a flexible or rigid tube inserted
into the nostril (or mouth). Sometimes cells are
collected by washing the lungs with a small amount
of fluid.
Computed tomography(CT)—A special x-ray technique that produces a cross sectional image of the
organs inside the body.
Corticosteroids—A class of drugs, related to hormones naturally found in the body, that suppress
the immune system. One example is prednisone,
sold under many brand names including
Deltasone.
End-stage lung disease—The final stages of lung
disease, when the lung can no longer keep the
blood supplied with oxygen. End-stage lungs in
pulmonary fibrosis have large air spaces separated
by bands of inflammation and scarring.
Farmer’s lung—An allergic reaction to moldy hay,
most often seen in farmers, that results in lung
disease.
Immune suppressant drug—Any drug that dampens
immune
responses
and
decreases
inflammation.
Inflammation—The body’s reaction to an irritant,
characterized by the accumulation of immune
cells, redness, and swelling.
Lung function tests—Tests of how much air the
lungs can move in and out, and how quickly and
efficiently this can be done. Lung function tests are
usually done by breathing into a device that measures air flow.
Mucous membranes—The moist coverings that
line the mouth, nose, intestines, and other internal
organs.
Pulmonary artery—The blood vessel that delivers
blood from the heart to the lungs.
Sarcoidosis—A disease of unknown origin that
results in clumps of immune cells and inflammation in organs throughout the body.

GALE ENCYCLOPEDIA OF MEDICINE

The prognosis depends on the specific disease.
Some cases may stop progressing or improve, particularly if the cause can be identified and treated. Others
may develop quickly or slowly into end-stage lung
disease. The course of idiopathic pulmonary fibrosis
is very difficult to predict; however, average survival is
approximately five to seven years.

Prevention
There is no known prevention for idiopathic pulmonary fibrosis.
Some ways to prevent other causes of pulmonary
fibrosis are:


avoid exposure to particle dust such as asbestos, coal
dust, and silica



avoid exposure to chemical fumes



do not smoke

Resources
BOOKS

Kobzik, Lester. ‘‘Diffuse Interstitial (Infiltrative,Restrictive)
Diseases.’’ In Robbins Pathologic Basis of Disease, edited by Ramzi S. Cotran, Vinay Kumar, and Tucker
Collins, 6th ed. Philadelphia: W.B. Saunders, 2000, pp.
727-740.
Toews, Galen B. ‘‘Interstitial Lung Disease.’’ InCecil
Textbook of Medicine, edited by Lee Goldman and J.
Claude Bennett, 21st ed. Philadelphia: W.B. Saunders,
2000,pp. 409-419.
PERIODICALS

Mason, Robert J., Marvin I. Schwarz, Gary W.
Hunninghake, and Robert A. Musson. ‘‘Pharmacologic
Therapy for Idiopathic Pulmonary Fibrosis: Past,
Present, and Future.’’ American Journal of Respiratory
and Critical CareMedicine 160 (1999): 1771-1777.
Michaelson, Jeffrey E., Samuel M. Aguayo, and Jesse
Roman. ‘‘Idiopathic Pulmonary Fibrosis: A Practical
Approach for Diagnosis and Management.’’ Chest 118,
no. 3 (September2000): 788-94.
ORGANIZATIONS

The American Lung Association. 1740 Broadway, New
York. NY 10019. (212) 315-8700. <http://
www.lungusa.org>.
Pulmonary Fibrosis Association. P.O. Box 75004, Seattle,
WA 98125-0004. (206) 417-0949. <http://
pulmonaryfibrosisassn.com>.
Pulmonary Fibrosis Foundation. 1075 Santa Fe Drive,
Denver, Colorado 80204. (720) 932-7850. <http://
pulmonaryfibrosis.org>.

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Pulmonary fibrosis

Prognosis

KEY TERMS

Pulmonary function test

OTHER

‘‘Bronchoscopy with Transtracheal Biopsy ’’Health
Encyclopedia. 2001. [cited May 2, 2001]. <http://
www.merck-medco.com/medco/index.jsp>.
Chronic Lung Disease Information Resource. The Cheshire
Medical Center. May 5, 2001. <http://www.cheshiremed.com/programs/pulrehab/rehinfof.html>.
‘‘Lung Needle Biopsy.’’ Health Encyclopedia. 2001. [cited
May 2, 2001]. <http://www.merck-medco.com/medco/
index.jsp>.
‘‘Open Lung Biopsy ’’ Health Encyclopedia. 2001. [cited May
2, 2001]. <http://www.merck-medco.com/medco/
index.jsp>.

fastest flow that is achieved, and the volume of air
exhaled in the first second of the test.
A peak flow meter can determine how much a
patient’s airways have narrowed. A test of blood
gases is a measurement of the concentration of oxygen
and carbon dioxide in the blood, which shows how
efficient the gas exchange is in the lungs.
Another lung function test reveals how efficient
the lungs are in absorbing gas from the blood. This is
measured by testing the volume of carbon monoxide a
person breathes out after a known volume of the gas
has been inhaled.

Anna Rovid Spickler, D.V.M., Ph.D.

Precautions

Pulmonary fibrosis see Idiopathic infiltrative
lung diseases

Pulmonary function test
Definition
Pulmonary function tests are a group of procedures that measure the function of the lungs, revealing
problems in the way a patient breathes. The tests can
determine the cause of shortness of breath and may
help confirm lung diseases, such as asthma, bronchitis
or emphysema. The tests also are performed before any
major lung surgery to make sure the person won’t be
disabled by having a reduced lung capacity.

Purpose
Pulmonary function tests can help a doctor diagnose a range of respiratory diseases which might not
otherwise be obvious to the doctor or the patient. The
tests are important since many kinds of lung problems
can be successfully treated if detected early.
The tests are also used to measure how a lung
disease is progressing, and how serious the lung disease has become. Pulmonary function tests also can be
used to assess how a patient is responding to different
treatments.
One of the most common of the pulmonary function tests is spirometry (from the Greco-Latin term
meaning ‘‘to measure breathing’’). This test, which can
be given in a hospital or doctor’s office, measures how
much and how fast the air is moving in and out of the
lungs. Specific measurements taken during the test
include the volume of air from start to finish, the
3108

Pulmonary function tests shouldn’t be given to
patients who have had a recent heart attack, or who
have certain other types of heart disease. It is crucial
that the patient cooperate with the health care team if
accurate results are to be obtained.

Description
The patient places a clip over the nose and
breathes through the mouth into a tube connected to
a machine known as a spirometer. First the patient
breathes in deeply, and then exhales as quickly and
forcefully as possible into the tube. The exhale must
last at least six seconds for the machine to work properly. Usually the patient repeats this test three times,
and the best of the three results is considered to be the
measure of the lung function. The results will help a
doctor figure out which type of treatment to pursue.

Preparation
The patient should not eat a heavy meal before the
test, nor smoke for four to six hours beforehand. The
patient’s doctor will issue specific instructions about
whether or not to use specific medications, including
bronchodilators or inhalers, before the test.
Sometimes, medication may be administered as part
of the test.

Risks
The risk is minimal for most people, although the
test carries a slight risk of a collapsed lung in some
patients with lung disease.

Normal results
Normal results are based on a person’s age, height,
and gender. Normal results are expressed as a percentage
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Ruppel, Gregg L. Manual of Pulmonary Function Testing. St.
Louis: Mosby, 1997.

Carol A. Turkington

Pulmonary heart disease see Cor pulmonale

Pulmonary hypertension
Definition
Pulmonary hypertension is a rare lung disorder
characterized by increased pressure in the pulmonary
artery. The pulmonary artery carries oxygen-poor
blood from the lower chamber on the right side of
the heart (right ventricle) to the lungs where it picks
up oxygen.

Description
Pulmonary hypertension is present when the
blood pressure in the circulation of the lungs is measured at greater than 25 mm of mercury (Hg) at rest or
30 mm Hg during exercise. Pulmonary hypertension
can be either primary or secondary:


Primary pulmonary hypertension. The cause of pulmonary hypertension is unknown. It is rare, affecting
one people per-million. The illness most often occurs
in young adults, especially women.



Secondary pulmonary hypertension. Secondary pulmonary hypertension is increased pressure of the
blood vessels of the lungs as a result of other medical
conditions.

This young girl is undergoing a pulmonary function test in
order to measure the functionality of her lungs. (Custom
Medical Stock Photo. Reproduced by permission.)

KEY TERMS
Emphysema—A disease in which the small air sacs
in the lungs become damaged, causing shortness of
breath. In severe cases it can lead to respiratory or
heart failure.

of the predicted lung capacity. The prediction takes into
account the patient’s age, height, and sex.

Regardless of whether pulmonary hypertension is
primary or secondary, the disorder results in thickening of the pulmonary arteries and narrowing of these
blood vessels. In response, the right side of the heart
works harder to move the blood through these arteries
and it becomes enlarged. Eventually overworking the
right side of the heart may lead to right-sided heart
failure, resulting in death.

Causes and symptoms
Abnormal results
Abnormal results mean that the person’s lung
capacity is less than 80% of the predicted value. Such
findings usually mean that there is some degree of
chest or lung disease.
GALE ENCYCLOPEDIA OF MEDICINE

While the cause of primary pulmonary hypertension is uncertain, researchers think that in most people
who develop the disease, the blood vessels are sensitive
to certain factors that cause them to narrow. Diet
suppressants, cocaine, and pregnancy are some of the
3109

Pulmonary hypertension

Resources

Pulmonary hypertension

KEY TERMS
Hypertension—The medical term for abnormally
high blood pressure.
Perfusion lung scan—A scan that shows the pattern
of blood flow in the lungs.
Pulmonary—Having to do with the lungs.
Pulmonary function test—A test that measures
how much air the lungs hold and the air flow in
and out of the lungs.
Right-heart cardiac catherization—A medical procedure during which a physician threads a catheter
into the right side of the heart to measure the blood
pressure in the right side of the heart and the pulmonary artery. The right heart’s pumping ability
can also be evaluated.

factors that are thought to trigger constriction or narrowing of the pulmonary artery. In about 6–10% of
cases, primary pulmonary hypertension is inherited.
Secondary pulmonary hypertension can be associated with breathing disorders such as emphysema
and bronchitis, or diseases such as scleroderma, systemic lupus erythematosus (SLE) or congenital heart
disease involving heart valves, and pulmonary
thromboembolism.
Symptoms of pulmonary hypertension include
shortness of breath with minimal exertion, general
fatigue, dizziness, and fainting. Swelling of the ankles,
bluish lips and skin, and chest pain are among other
symptoms of the disease.

Diagnosis
Pulmonary hypertension is rarely detected during
routine physical examinations and, therefore, often
progresses to later stages before being diagnosed.
In addition to listening to heart sounds with a stethoscope, physicians also use electrocardiogram, pulmonary function tests, perfusion lung scan, and/or
right-heart cardiac catheterization to diagnose pulmonary hypertension.

Treatment
The aim of treatment for pulmonary hypertension
is to treat the underlying cause, if it is known. For
example, thromboendarterectomy is a surgical procedure performed to remove a blood clot on the lung
3110

that is causing the pulmonary hypertension. Lung
transplants are another surgical treatment.
Some patients are helped by taking medicines that
make the work of the heart easier. Anticoagulants,
drugs that thin the blood, decrease the tendency of
the blood to clot and allow blood to flow more freely.
Diuretics decrease the amount of fluid in the body and
reduce the amount of work the heart has to do.
Calcium channel blockers relax the smooth muscle in
the walls of the heart and blood vessels and improve
the ability of the heart to pump blood.
One effective medical treatment that dilates blood
vessels and seems to help prevent blood clots from
forming is epoprostenol (prostacyclin). Prostacyclin is
given intravenously to improve survival, exercise duration, and well-being. It is sometimes used as a bridge to
help people who are waiting for a lung transplant. In
other cases it is used for long-term treatment.
Some people require supplemental oxygen
through nasal prongs or a mask if breathing becomes
difficult.

Prognosis
Pulmonary hypertension is chronic and incurable
with an unpredictable survival rate. Length of survival
has been improving, with some patients able to live
15–20 years or longer with the disorder.

Prevention
Since the cause of primary pulmonary hypertension is still unknown, there is no way to prevent or cure
this disease. A change in lifestyle may assist patients
with daily activities. For example, relaxation exercises
help to reduce stress. Good health habits such as a
healthy diet, not smoking, and getting plenty of rest
should be maintained.
Resources
ORGANIZATIONS

American Association for Respiratory Care. 11030 Ables
Lane, Dallas, TX 75229. (972) 243-2272. <http://
www.aarc.org>.
Pulmonary Hypertension Association. P.O. Box 24733,
Speedway, IN 46224-0733. (800) 748-7274. <http://
www.phassociation.org>.
OTHER

‘‘Primary Pulmonary Hypertensiton.’’ National Heart,
Lung, and Blood Institute. <http://www.nhlbi.nih.gov/
nhlbi/lung/other/gp/pph.txt>.

Lorraine Steefel, RN
GALE ENCYCLOPEDIA OF MEDICINE

Pulmonary regurgitation see Pulmonary
valve insufficiency
Pulmonary stenosis see Pulmonary valve
stenosis

Pulmonary valve insufficiency
Definition
Pulmonary valve insufficiency is a disorder involving a defect of the valve located in the pulmonary
artery.

Description
This disorder is also known as pulmonary valve
regurgitation or pulmonary incompetence. The pulmonary valve is the structure in the pulmonary artery
consisting of three flaps, which open and close during
each heartbeat. The flaps keep blood from flowing
back into the heart from the pulmonary artery–the
artery that supplies blood to the lungs. With pulmonary valve insufficiency, the flaps may allow the blood
to flow backward, resulting in a distinct murmur. The
disorder may be congenital, but also often occurs in
patients with severe pulmonary hypertension.

Causes and symptoms
There are generally few to no symptoms with
pulmonary valve insufficiency. It may be initially
noticed as a murmur in a routine exam of the heart
and chest with a stethoscope. The most common
causes of the disorder are severe pulmonary hypertension, or the presence of high pressure in the arteries
and veins of the lungs. Pulmonary hypertension is
usually caused by chronic lung disease, lung blood
clots, and sometimes other diseases, such as endocarditis, an inflammation of the lining of the heart and
valves. Previous surgery for congenital heart disease
may also cause pulmonary valve insufficiency.

Diagnosis
The pitch and location of the murmur will help
a physician determine if the cause is pulmonary
valve insufficiency. An electrocardiogram (EKG)
can detect flow changes. Echocardiography with
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Congenital—Used to describe a condition or defect
present at birth.
Endocarditis—Inflammation of the lining of the
heart and valves.
Prophylaxis—Preventive. Antibiotic prophylaxis is
the use of antibiotics to prevent a possible
infection.
Pulmonary—Refers to the lungs and the breathing
system and function.
Pulmonary hypertension—High blood pressure in
the veins and arteries of the lungs.

color Doppler can usually detect regurgitation of
blood in the area. This exam is done with ultrasound imaging. A chest x ray may show prominence
of the pulmonary artery. In some cases, angiocardiography, or x ray of the arteries and vessels with
injection of a dye, may be ordered.

Treatment
On its own, pulmonary valve insufficiency is seldom severe enough to require treatment. Antibiotics
are usually recommended before dental work to
reduce the possibility of bacterial endocarditis.
Management of the primary condition, such as medications to manage pulmonary hypertension, may help
control pulmonary valve insufficiency.

Alternative treatment
Since there are few or no symptoms and the disorder is a structural defect, alternative treatment may
have only limited usefulness. Proper diet, exercise, and
stress reduction may help control hypertension.
Coenzyme Q10 and hawthorn (Crataegus laevigata)
are two important nutrients to nourish the heart.
Antioxidant supplements (including vitamins A, C,
and E, selenium, and zinc) can help keep the tissues
of the whole body, including the heart, in optimal
condition.

Prognosis
Patients with this disorder may never experience
limitations from pulmonary valve insufficiency. The
disorder may only show up if complicated by pulmonary hypertension. There is an increased incidence of
3111

Pulmonary valve insufficiency

Pulmonary incompetence see Pulmonary
valve insufficiency

Pulmonary valve stenosis

bacterial endocarditis in patients with pulmonary
valve insufficiency. Endocarditis can progress rapidly
and be fatal.

Prevention
Pulmonary valve insufficiency resulting from
chronic lung diseases can be prevented by behaviors
and interventions to prevent those primary diseases.
Bacterial endocarditis resulting from pulmonary valve
insufficiency can usually be prevented with the use of
antibiotic prophylaxis in preparation for dental procedures or other procedures which may introduce bacteria into the bloodstream.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300 or (800) 242-8721. inquire@heart.org <http://www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Teresa Odle

Causes and symptoms
Pulmonary valve stenosis is caused by a congenital malformation in which the pulmonary valve does
not open properly. In most cases, scientists don’t know
why it occurs. In cases of mild or moderate stenosis,
there are often no symptoms. With more severe
obstruction, symptoms include a bluish skin tint and
signs of heart failure.

Diagnosis
Diagnosis of pulmonary valve stenosis begins with
the patient’s medical history and a physical exam. Tests
to confirm the diagnosis include chest x ray, echocardiogram, electrocardiogram, and catherization. An
electrocardiograph shows the heart’s activity.
Electrodes covered with conducting jelly are placed on
the patient. The electrodes send impulses that are traced
on a recorder. Echocardiography uses sound waves to
create an image of the heart’s chambers and valves. The
technician applies gel to a wand (transducer) and
presses it against the patient’s chest. The returning
sound waves are converted into an image displayed on
a monitor. Catherization is an invasive procedure used
to diagnose, and in some cases treat, heart problems. A
thin tube, called a catheter, is inserted into a blood
vessel and threaded up into the heart, enabling physicians to see and sometimes correct the problems.

Treatment

Pulmonary valve stenosis
Definition
Pulmonary valve stenosis is a congenital heart
defect in which blood flow from the heart to the pulmonary artery is blocked.

Description
Pulmonary valve stenosis is an obstruction in the
pulmonary valve, located between the right ventricle
and the pulmonary artery. Normally, the pulmonary
valve opens to let blood flow from the right ventricle to
the lungs. When the pulmonary valve is malformed, it
forces the right ventricle to pump harder to overcome
the obstruction. In its most severe form, pulmonary
valve stenosis can be life-threatening.
Patients with pulmonary valve stenosis are at
increased risk for getting valve infections and must
take antiobiotics to help prevent this before certain
dental and surgical procedures. Pulmonary valve stenosis is also called pulmonary stenosis.
3112

Patients with mild to moderate pulmonary valve
stenosis, and few or no symptoms, do not require
treatment. In more severe cases, the blocked valve
will be opened surgically, either through balloon valvuloplasty or surgical valvulotomy. For initial treatment,
balloon valvuloplasty is the procedure of choice. This
is a catherization procedure in which a special catheter
containing a deflated balloon is inserted in a blood
vessel and threaded up into the heart. The catheter is
positioned in the narrowed heart valve and the balloon
is inflated to stretch the valve open.
In some cases, surgical valvulotomy may be necessary. This is open heart surgery performed with a
heart-lung machine. The valve is opened with an incision and in some cases, hypertrophied muscle in the
right ventricle is removed. Rarely does the pulmonary
valve need to be replaced.

Alternative treatment
Pulmonary valve stenosis can be life threatening
and always requires a physician’s care. In mild to
GALE ENCYCLOPEDIA OF MEDICINE

Congenital—Present at birth.

Pustule see Skin lesions

Pulmonary—Relating to the opening leading from
the right large chamber of the heart into the lung
artery.

Pyelography see Intravenous urography

Stenosis—A narrowing or constriction, in this case
of various heart valves. Stenosis reduces or cuts off
the flow of blood.
Valve—Tissue between the heart’s upper and lower
chambers that controls blood flow.

moderate cases of pulmonary valve stenosis, general
lifestyle changes, including dietary modifications,
exercise, and stress reduction, can contribute to maintaining optimal wellness.

Prognosis
Patients with the most severe form of pulmonary
valve stenosis may die in infancy. The prognosis for
children with more severe stenosis who undergo balloon valvuloplasty or surgical valvulotomy is favorable. Patients with mild to moderate pulmonary
stenosis can lead a normal life, but they require regular
medical care.

Pyelonephritis

Purpura hemorrhagica see Idiopathic
thrombocytopenic purpura

KEY TERMS

Pyelonephritis
Definition
Pyelonephritis is an inflammation of the kidney
and upper urinary tract that usually results from noncontagious bacterial infection of the bladder (cystitis).

Description
Acute pyelonephritis is most common in adult
females but can affect people of either sex and any
age. Its onset is usually sudden, with symptoms that
often are mistaken as the results of straining the lower
back. Pyelonephritis often is complicated by systemic
infection. Left untreated or unresolved, it can progress
to a chronic condition that lasts for months or years,
leading to scarring and possible loss of kidney
function.

Causes and symptoms
Prevention
Pulmonary valve stenosis cannot be prevented.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
Children’s Health Information Network. 1561 Clark Drive,
Yardley, PA 19067. (215) 493-3068. <http://
www.tchin.org>.
Congenital Heart Anomalies Support, Education &
Resources, Inc. 2112 North Wilkins Road, Swanton,
OH 43558. (419) 825-5575. <http://www.csun.edu/
~hfmth006/chaser>.
Texas Heart Institute. Heart Information Service. P.O. Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto

Punctures see Wounds
Purple coneflower see Echinacea
GALE ENCYCLOPEDIA OF MEDICINE

The most common cause of pyelonephritis is the
backward flow (reflux) of infected urine from the
bladder to the upper urinary tract. Bacterial infections
also may be carried to one or both kidneys through the
bloodstream or lymph glands from infection that
began in the bladder. Kidney infection sometimes
results from urine that becomes stagnant due to
obstruction of free urinary flow. A blockage or
abnormality of the urinary system, such as those
caused by stones, tumors, congenital deformities, or
loss of bladder function from nerve disease, increases a
person’s risk of pyelonephritis. Other risk factors
include diabetes mellitus, pregnancy, chronic bladder
infections, a history of analgesic abuse, paralysis from
spinal cord injury, or tumors. Catheters, tubes, or surgical procedures may also trigger a kidney infection.
The bacteria most likely to cause pyelonephritis
are those that normally occur in the feces. Escherichia
coli causes about 85% of acute bladder and kidney
infections in patients with no obstruction or history of
surgical procedures. Klebsiella, Enterobacter, Proteus,
or Pseudomonas are other common causes of infection. Once these organisms enter the urinary tract,
3113

Pyelonephritis

they cling to the tissues that line the tract and multiply
in them.
Symptoms of acute pyelonephritis typically
include fever and chills, burning or frequent urination,
aching pain on one or both sides of the lower back or
abdomen, cloudy or bloody urine, and fatigue. The
patient also may have nausea, vomiting, and diarrhea.
The flank pain may be extreme. The symptoms of
chronic pyelonephritis include weakness, loss of appetite, hypertension, anemia, and protein and blood in
the urine.

KEY TERMS
Bacteremia—The presence of bacteria in the
bloodstream.
Cystitis—Inflammation of the bladder, usually
caused by bacterial infection.
Reflux—The backward flow of a fluid in the body.
Pyelonephritis is often associated with the reflux of
urine from the bladder to the upper urinary tract.

Diagnosis
The diagnosis of pyelonephritis is based on the
patient’s history, a physical examination, and the
results of laboratory and imaging tests. During the
physical examination, the doctor will touch (palpate)
the patient’s abdomen carefully in order to rule out
appendicitis or other causes of severe abdominal pain.
Laboratory tests
In addition to collecting urine samples for urinalysis and urine culture and sensitivity tests, the doctor
will take a sample of the patient’s blood for a blood
cell count. If the patient has pyelonephritis, the urine
tests will show the presence of white blood cells, and
bacteria in the urine. Bacterial counts of 100,000
organisms or higher per milliliter of urine point to a
urinary tract infection. The presence of antibodycoated bacteria (ACB) in the urine sample distinguishes kidney infection from bladder infection,
because bacteria in the kidney trigger an antibody
response that coats the bacteria. The blood cell count
usually indicates a sharp increase in the number of
white blood cells.
Imaging studies
The doctor may order ultrasound imaging of the
kidney area if he or she suspects that there is an
obstruction blocking the flow of urine. X rays may
demonstrate scarring of the kidneys and ureters resulting from long-standing infection.

Treatment
Treatment of acute pyelonephritis may require
hospitalization if the patient is severely ill or has complications. Therapy most often involves a two- to
three-week course of antibiotics, with the first few
days of treatment given intravenously. The choice of
antibiotic is based on laboratory sensitivity studies.
The antibiotics used most often include ciprofloxacin
3114

(Cipro), ampicillin (Omnipen), or trimethoprim-sulfamethoxazole (Bactrim, Septra). Several advances in
antibiotic therapy have been made in recent years. In
2003, the U.S. Food and Drug Administration (FDA)
approved Cipro extended release tablets (Cipro XR)
that could be taken once daily for acute uncomplicated pyelonephritis. A study in Europe also showed
that a shorter course than that normally used in the
United States could eradicate the bacteria that cause
the disease. The primary objective of antimicrobial
therapy is the permanent eradication of bacteria
from the urinary tract. The early symptoms of pyelonephritis usually disappear within 48 to 72 hours of the
start of antibacterial treatment. Repeat urine cultures
are done in order to evaluate the effectiveness of the
medication.
Chronic pyelonephritis may require high doses of
antibiotics for as long as six months to clear the infection. Other medications may be given to control fever,
nausea, and pain. Patients are encouraged to drink
extra fluid to prevent dehydration and increase urine
output. Surgery sometimes is necessary if the patient
has complications caused by kidney stones or other
obstructions, or to eradicate infection. Urine cultures
are repeated as part of the follow-up of patients with
chronic pyelonephritis. These repeat tests are necessary to evaluate the possibility that the patient’s urinary tract is infected with a second organism as well as
to assess the patient’s response to the antibiotic. Some
persons are highly susceptible to reinfection, and a
second antibiotic may be necessary to treat the
organism.

Prognosis
The prognosis for most patients with acute pyelonephritis is quite good if the infection is caught early
and treated promptly. The patient is considered cured
if the urine remains sterile for a year. Untreated or
recurrent kidney infection can lead to bacterial
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Persons with a history of urinary tract infections should urinate frequently, and drink plenty of
fluids at the first sign of infection. Women should
void after intercourse which may help flush bacteria from the bladder. Girls should be taught to
wipe their genital area from front to back after
urinating to avoid getting fecal matter into the
opening of the urinary tract.
Resources
PERIODICALS

Jancin, Bruce. ‘‘Short-course Cipro for Pyelonephritis:
Unapproved Regimen Shows Promise.’’ OB GYN News
November 1, 2003: 5.
Mangan, Doreen. ‘‘The FDA has Approved Ciprofloxacin
Extended Release Tavlets (Cipro XR), a Once-daily
Formulation, for the Treatment of Complicated
Urinary Tract Infections (cUTIs) and Acute
Pyelonephritis (AUP), or Kidney Infection.’’ RN
November 2003: 97.
Raz, Paul, et al. ‘‘Long-term Follow-up of Women
Hospitalized for Acute Pyelonephritis.’’ Clinical
Infectious Diseases (October 15, 2003):1014–1017.
ORGANIZATIONS

American Foundation for Urologic Disease. 1128 N.
Charles St., Baltimore, MD 21201. (401) 468-1800.
<http://www.afud.org>.

Kathleen D. Wright, RN
Teresa G. Odle

Pyloric stenosis
Definition
Pyloric stenosis refers to a narrowing of the
passage between the stomach and the small intestine. The condition, which affects infants during
the first several weeks of life, can be corrected
effectively with surgery.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Frequent vomiting may be an indication of pyloric
stenosis. The pylorus is the passage between the stomach and the small intestine. During the digestive
process food passes through the pylorus, which is
located near the bottom of the stomach, on its way
to the intestines. In pyloric stenosis, the muscular wall
of the passage becomes abnormally thickened. This
causes the pylorus to become too narrow, which prevents food from emptying out of the stomach in a
normal fashion. The partially digested contents of
the stomach are forced upwards into the mouth. As a
result, a baby with pyloric stenosis often vomits after
feedings.
The condition affects one in 4,000 infants. Most
are diagnosed between three and five weeks old,
though some babies may show symptoms during the
first or second week of life. Infants with a family
history of pyloric stenosis are more at risk for the
condition, which tends to occur less often in females,
blacks, and Asians. Pyloric stenosis is also referred to
as hypertrophic pyloric stenosis.

Causes and symptoms
The cause of pyloric stenosis is not known. The
main symptom is vomiting after feedings. These episodes of vomiting usually get worse over time, happening more often and becoming more forceful (forceful
vomiting is often called ‘‘projectile’’ vomiting). Other
symptoms include increased appetite, weight loss,
infrequent bowel movements, belching, and diarrhea.
Due to dehydration, the infant may also have fewer wet
diapers.

Diagnosis
The clinician will examine the baby and talk with
the parents about their infant’s symptoms. If a child
has the condition, the doctor should be able to feel a
hard mass (about 2 cm wide and olive shaped) in the
area above the bellybutton. If the doctor cannot
detect the mass, ultrasonography will be done to
confirm the diagnosis. A blood test may also be performed to see if the infant is dehydrated, in which
case intravenous fluids can be used to correct the
problem.

Treatment
Pyloric stenosis can be cured with a surgical
procedure called a pyloromyotomy. In this operation, the surgeon makes an incision in the baby’s
3115

Pyloric stenosis

invasion of the bloodstream (bacteremia), hypertension, chronic pyelonephritis with scarring of the kidneys, and permanent kidney damage. In 2003, a report
on long-term follow-up of adults with acute pyelonephritis looked at kidney scarring and resulting complications. Kidney damage that causes complications
is rare after 10 to 20 years, even though many women
showed renal scarring.

Pyloroplasty

ORGANIZATIONS

KEY TERMS
Laparoscope—A thin, camera-fitted tube that can
be inserted into the abdomen in order to view
internal organs.
Stenosis—The narrowing of a passage (such as the
pylorus).

American Academy of Family Physicians. 11400 Tomahawk
Creek Parkway, Leawood, KS 66211-2672. (913) 9066000. <http://www.aafp.org/>. fp@aafp.org.
American Academy of Pediatrics. 141 Northwest Point
Boulevard, Elk Grove Village, IL 60007-1098. (847)
434-4000. <http://www.aap.org>.

Greg Annussek

Ultrasonography—A non-invasive imaging procedure that uses high-frequency sound waves.

abdomen. Then a small cut is made in the thickened
muscle of the pylorus and it is spread apart. In this
manner, the passage can be widened without removing any tissue. (The procedure may be performed
with the aid of a laparoscope.) After surgery, the
pylorus will heal itself. The thickening gradually
goes away and the passage resumes a normal
shape. The whole procedure (including anesthesia)
takes about an hour.
Most babies go home one or two days after surgery. Any mild discomfort can be controlled with
Tylenol. The infant may still vomit occasionally after
surgery, but this is not usually a cause for alarm.
However, if vomiting occurs three or more times a
day, or for several consecutive days, the baby’s pediatrician should be notified.

Alternative treatment
None known.

Prognosis
Surgery is often a complete cure. Most infants do
not experience complications or long-term effects.

Prevention
It is not known how to prevent pyloric stenosis.
Resources
BOOKS

Behrman, Richard E., et al., Nelson Textbook of Pediatrics.
Philadelphia: WB Saunders, 2000.
PERIODICALS

Yoshizawa J, et al. Ultrasonographic Features of
Normalizationof the Pylorus after Pyloromyotomy for
Hypertrophic Pyloric Stenosis. ‘‘Journal of
PediatricSurgery’’ 36 (April 2001): 582-6.
3116

Pyloroplasty
Definition
Pyloroplasty is an elective surgical procedure in
which the lower portion of the stomach, the pylorus, is
cut and resutured, to relax the muscle and widen the
opening into the intestine. Pyloroplasty is a treatment
for high-risk patients for gastric or peptic ulcer disease. A peptic ulcer is a well-defined sore on the stomach where the lining of the stomach or duodenum
has been eaten away by stomach acid and digestive
juices.

Purpose
The end of the pylorus is surrounded by a strong
band of muscle (pyloric sphincter), through which
stomach contents are emptied into the duodenum
(the first part of the small intestine). Pyloroplasty
widens this opening into the duodenum.
A pyloroplasty is performed to treat complications of gastric ulcer disease, or when conservative
treatment is unsatisfactory. The longitudinal cut
made in the pylorus is closed transversely, permitting
the muscle to relax. By establishing an enlarged outlet
from the stomach into the intestine, the stomach empties more quickly. A pyloroplasty is often done is
conjunction with a vagotomy, a procedure in which
the nerves that stimulate stomach acid production and
gastric motility (movement) are cut. As these nerves
are cut, gastric emptying may be delayed, and the
pyloroplasty compensates for that effect.

Preparation
As with any surgical procedure, the patient will be
required to sign a consent form after the procedure is
explained thoroughly. Blood and urine studies, along
with various x rays may be ordered as the doctor
deems necessary. Food and fluids will be prohibited
GALE ENCYCLOPEDIA OF MEDICINE

Gastric (or peptic) ulcer—An ulcer (sore) of the
stomach, duodenum or other part of the gastrointestinal system. Though the causes are not fully
understood, they include excessive secretion of
gastric acid, stress, heredity, and the use of certain
drugs, especially acetylsalicylic acid and nonsteroidal antiinflammatory drugs.
Pylorus—The valve which releases food from the
stomach into the intestines.
Vagotomy—Cutting of the vagus nerve. If the vagus
nerves are cut as they enter the stomach (truncal
vagotomy), gastric secretions are decreased, as is
intestinal motility (movement) and stomach emptying. In a selective vagotomy, only those branches of
the vagus nerve are cut that stimulate the secretory
cells.

after midnight before the procedure. Cleansing enemas
may be ordered to empty the intestine. If nausea or
vomiting are present, a suction tube to empty the stomach may be used.



incisional hernia



recurrence of gastric ulcer



chronic diarrhea



malnutrition

Normal results
Complete healing is expected without complications. Four to six weeks should be allowed for recovery from the surgery.

Abnormal results
The doctor should be made aware of any of the
following problems after surgery:


increased pain, swelling, redness, drainage, or bleeding in the surgical area



headache, muscle aches, dizziness, or fever



increased abdominal pain or swelling, constipation,
nausea or vomiting, rectal bleeding, or black, tarry
stools

Resources
OTHER

‘‘Peptic ulcer surgery. ’’ThriveOnline. April 20, 1988.
<http://thriveonline.oxygen.com>.

Aftercare
Post-operative care for the patient who has had a
pyloroplasty, as for those who have had any major
surgery, involves monitoring of blood pressure, pulse,
respiration, and temperature. Breathing tends to be
shallow because of the effect of anesthesia and the
patient’s reluctance to breathe deeply and experience
pain that is caused by the abdominal incision. The
patient is shown how to support the operative site
while breathing deeply and coughing, and given pain
medication as necessary. Fluid intake and output is
measured, and the operative site is observed for color
and wound drainage. Fluids are given intravenously for
24–48 hours, until the patient’s diet is gradually
advanced as bowel activity resumes. The patient is generally allowed to walk approximately eight hours after
surgery and the average hospital stay, dependent upon
overall recovery status, ranges from six to eight days.

Risks
Potential complications of this abdominal surgery
include:


excessive bleeding



surgical wound infection

GALE ENCYCLOPEDIA OF MEDICINE

Kathleen D. Wright, RN

Pylorus repair see Pyloroplasty
Pyorrhea see Periodontal disease
Pyrazinamide see Antituberculosis drugs
Pyridoxine deficiency see Vitamin B6
deficiency
Pyrimethamine see Antimalarial drugs

Pyruvate kinase deficiency
Definition
Pyruvate kinase deficiency (PKD) is part of a
group of disorders called hereditary nonspherocytic
hemolytic anemias. Hereditary nonspherocytic anemias are rare genetic conditions that affect the red
blood cells. PKD is caused by a deficiency in the
enzyme, pyruvate kinase. Although PKD is the second
most common of the hereditary nonspherocytic
3117

Pyruvate kinase deficiency

KEY TERMS

Pyruvate kinase deficiency

anemias, it is still rare, with the incidence estimated to
be 51 cases per million in the Caucasian population.

Description
In PKD, there is an functional abnormality with
the enzyme, pyruvate kinase. Usually, pyruvate kinase
acts as a catalyst in the glycolysis pathway, and is
considered an essential component in this pathway.
Glycolysis is the method by which cells produce their
own energy. A problem with any of the key components in glycolysis can alter the amount of energy
produced. In the red blood cells, glycolysis is the only
method available to produce energy. Without the
proper amount of energy, the red blood cells do not
function normally. Since pyruvate kinase is one of the
key components in glycolysis, when there is a problem
with this enzyme in the red blood cells, there is a
problem with the production of energy, causing the
red blood cells not to function properly.
There are four different forms of the pyruvate
kinase enzyme in the human body. These forms, called
isozymes, all perform the same function but each isozyme of pyruvate kinase is structurally different and
works in different tissues and organs. The four isozymes of pyruvate kinase are labeled M1, M2, L, and
R. The isozyme M1 is found in the skeletal muscle and
brain, isozyme M2 can be found in most fetal and
adult tissues, isozyme L works in the liver, and isozyme R works in the red blood cells. In PKD, only the
pyruvate kinase isozyme found in red blood cells,
called PKR, is abnormal. Therefore, PKD only affects
the red blood cells and does not directly affect the
energy production in the other organs and tissues of
the body.
In general, PKD not does appear to affect one
gender more than another or be more common in
certain regions. However, there are studies of an
Amish group in Pennsylvania where a severe form of
PKD is more common. As previously mentioned, the
three mutations found in the PKLR gene have been
linked to individuals of specific decents. Caucasians of
northern and central European decent are more likely
to have the 1529A mutations, individuals of southern
European descent usually have the 1456T mutation,
and individuals of Asian descent are more likely to
have the 1468T mutation.

Causes and symptoms
There are two PK genes and each gene produces
two of the four isozymes of pyruvate kinase. The M1
and M2 isozymes are produced by the pyruvate kinase
3118

gene called PKM2 and pyruvate kinase isozymes, L
and R, are products of the pyruvate kinase gene,
PKLR. The PKLR gene is located on chromosome
1, on the q arm (the top half of the chromosome), in
region 21 (written as 1q21). As of 2001, there have
been over 125 different mutations described in the
PKLR gene that have been detected in individuals
with PKD.
PKD is mainly inherited in an autosomal recessive
manner. There have been a few families where it
appeared that PKD was inherited in either an autosomal dominant manner or where the carriers of PKD
exhibited mild problems with their red blood cells. As
with all autosomal recessive conditions, affected individuals have a mutation in both pair of genes. Most
individuals with PKD are compound heterozygotes,
meaning that each PKLR gene in a pair contains a
different mutation. There are individuals who have the
same mutation on each PKLR gene, but these individuals tend to be children of parents who are related to
each other.
There are three mutations in the PKLR gene
called, 1529A, 1456T, and 1468T, that are seen more
frequently in individuals with PKD than the other
mutations. The mutation 1529A is most frequently
seen in Caucasians of northern and central European
descent and is the most common mutation seen in
PKD. The mutation 1456T is more common in individuals of southern European descent and the mutation
1468T is more common in individuals of Asian
descent.
In general, the more severe the PKD, the earlier in
life symptoms tend to be detected. Individuals with the
more severe form of PKD often show symptoms soon
after birth, but most individuals with PKD begin to
exhibit symptoms during infancy or childhood. In
individuals with the more mild form of PKD, the
condition is sometimes not diagnosed until late adulthood, after an acute illness, or during a pregnancy
evaluation.
For most of the mutations seen in the PKLR gene,
no correlation between the specific mutation and the
severity of the disorder has been observed. However,
for two of the mutations, there has been speculation
on their effect on the severity of PKD. When the
mutation 1456T has been seen in the homozygous
state (when both PKLR genes contain the same mutation), those rare individuals experienced very mild
symptoms of PKD. Also, there have been individuals
who were homozygous for the 1529A mutation. These
individuals had a very severe form of PKD. Therefore,
it is thought that the 1456T mutation is associated
GALE ENCYCLOPEDIA OF MEDICINE

the same family, individuals can have different symptoms and severity of PKD.

Anemia—When the amount of red blood cells is
less than normal.
Catalyst—A substance that causes the next step in a
pathway or reaction to occur, but is not physically
changed by the process.

In individuals with PKD, the red blood cells are
taken out of their circulation earlier than normal
(shorten life-span). Because of this, individuals with
PKD will have hemolytic anemia. Additionally, the
anemia or other symptoms of PKD may worsen during a sudden illness or pregnancy.

Compound heterozygotes—Individuals who have
one gene in a pair with one mutation and the other
gene in the pair has a different mutation.
Enzyme—A protein produced by cells that acts as a
catalyst to allow a change or function to occur.
Glycolysis—The pathway in which a cell breaks
down glucose into energy.
Hemolytic anemia—Anemia that results from red
blood cells being destroyed sooner than normal.
Heterozygote/Heterozygotes—Are
individuals
who have one gene in a pair that has a mutation
while the other gene in the pair is unaffected.
Homozygote/Homozygotes—Are individuals who
have both genes in a pair with the same mutation.
Homozygous—When both genes in a pair have the
same mutation.
Isozyme/Isoenzyme—Are a group of enzymes that
perform the same function, but are different from
one another in their structure or how they move.
Mutation—A change in the gene that causes it to
alter its function
Nonspherocytic—Literally means not sphereshaped. Often in inherited hemolytic anemias, the
red blood cells are sphere-shaped. In Nonspherocytic Hemolytic Anemias, the red blood cells are
not sphere-shaped.

with a milder form of the disease and the 1529A mutation is associated with a more severe form of the disease. It is not known how these mutations affect the
severity of PKD when paired with different mutations.
Symptoms of PKD are similar to those symptoms
seen in individuals who have long-term hemolytic anemia. The more common symptoms include variable
degrees of jaundice (a yellowish pigment of the skin),
slightly to moderately enlarged spleen (splenomegaly),
and increased incidence of gallstones. Other physical
effects of PKD can include smaller head size and the
forehead appearing prominent and rounded (called
frontal bossing). If a child with PKD has their spleen
removed, their growth tends to improve. Even within
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
A diagnosis of PKD can be made by measuring
the amount of pyruvate kinase in red blood cells.
Individuals with PKD tend to have 5–25% of the
normal amount of pyruvate kinase. Carriers of PKD
also can have less pyruvate kinase in their red blood
cells, approximately 40–60% of the normal value.
However, there is an overlap between the normal
range of pyruvate kinase and the ranges seen with
carriers of PKD. Therefore, measuring the amount
of pyruvate kinase in the red blood cells is not a
good method of detecting carriers of PKD. If the
mutations causing PKD in a family are known, it
may be possible to perform mutation analysis to determine carrier status of an individual and to help diagnose individuals with PKD.

Treatment
In the severest cases, individuals with PKD will
require multiple blood transfusions. In some of those
cases, the spleen may be removed (splenectomy). Red
blood cells are normally removed from circulation by
the spleen. By removing an individual’s spleen (usually
a child), the red blood cells are allowed to stay in
circulation longer than normal; thereby, reducing the
severity of the anemia. After a splenectomy, or once an
individual with PKD is older, the number of transfusions tends to decrease.

Prognosis
The prognosis of PKD is extremely variable.
Early intervention and treatment of symptoms frequently improves the individual’s health. Without
treatment, individuals may experience severe complications that may become lethal. Individuals with a
mild form of PKD may appear to have no symptoms
at all.
Resources
PERIODICALS

Beutler, Ernest, and Terri Gelbart. ‘‘Estimating the
Prevalence of Pyruvate Kinase Deficiency from the
3119

Pyruvate kinase deficiency

KEY TERMS

Pyruvate kinase deficiency

Gene Frequency in the General White Population.’’
Blood 95 (June 2000): 3585-3588.
Kugler, W., et. al. ‘‘Eight Novel Mutations and
Consequences of mRNA and Protein Level in Pyruvate
Kinase Deficient Patients with Nonspherocytic
Hemolytic Anemia.’’ Human Mutation 15 (2000):
261-272.

OTHER

‘‘Entry 266200: Pyruvate Kinase Deficiency of
Erythrocyte.’’ OMIM—Online Mendelian Inheritance
in Man. <http://www.ncbi.nih.gov/htbin-post/Omim/
dispmim?266200>.

Sharon A. Aufox, MS, CGC

ORGANIZATIONS

NIH/National Heart, Lung, and Blood Institute. 31 Center
Drive.

3120

Pyschogenic disorder see Somatoform
disorders

GALE ENCYCLOPEDIA OF MEDICINE

Q
Q fever
Definition
Q fever is an illness caused by a type of bacteria,
Coxiella burnetii, resulting in a fever and rash.

Description
C. burnetii lives in many different kinds of animals,
including cattle, sheep, goats, ticks, cats, rabbits, birds,
and dogs. In sheep and cattle, for example, the bacteria
tends to accumulate in large numbers in the female’s
uterus (the organ where lambs and calves develop)
and udder. Other animals have similar patterns of bacterial accumulation within the females. As a result,
C. burnetii can cause infection through contaminated
milk, or when humans come into contact with the fluids
or tissues produced when a cow or sheep gives birth.
Also, the bacteria can survive in dry dust for months;
therefore, if the female’s fluids contaminate the ground,
humans may become infected when they come in contact with the contaminated dust.
Persons most at risk for Q fever include anybody
who works with cattle or sheep, or products produced
from them. These include farm workers, slaughterhouse workers, workers in meat-packing plants, veterinarians, and wool workers. Since September 2001,
however, Q fever has become an additional concern
because of its potential as an agent of bioterrorism.
Q fever has been found all over the world, except
in some areas of Scandinavia, Antarctica, and New
Zealand.

Causes and symptoms
C. burnetii causes infection when a human
breathes in tiny droplets, or drinks milk, containing
the bacteria. After three to 30 days, symptoms of the
illness appear.
GALE ENCYCLOPEDIA OF MEDICINE

The usual symptoms of Q fever include fever,
chills, heavy sweating, headache, nausea and vomiting,
diarrhea, fatigue, and cough. Also, a number of other
problems may present themselves, including inflammation of the liver (hepatitis); inflammation of the sac
containing the heart (pericarditis); inflammation of the
heart muscle itself (myocarditis); inflammation of the
coverings of the brain and spinal cord, or of the brain
itself (meningoencephalitis); and pneumonia.
Chronic Q fever occurs most frequently in
patients with other medical problems, including diseased heart valves, weakened immune systems, or kidney disease. Such patients usually have about a year’s
worth of vague symptoms, including a low fever,
enlargement of the spleen and/or liver, and fatigue.
Testing almost always reveals that these patients have
inflammation of the lining of the heart (endocarditis).

Diagnosis
Q fever is diagnosed by demonstrating that the
patient’s immune system is making increasing numbers of antibodies (special immune cells) against markers (antigens) that are found on C. burnetii.

Treatment
Doxycycline and quinolone antibiotics are effective for treatment of Q fever. Treatment usually lasts
for two weeks. Rifampin and doxycycline together are
given for chronic Q fever. Chronic Q fever requires
treatment for at least three years.
Minocycline has been found to be useful in treating post-Q fever fatigue. The dosage is 100 mg per day
for three months.

Prognosis
Death is rare from Q fever. Most people recover
completely, although some patients with endocarditis
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Qigong

KEY TERMS
Antibodies—Specialized cells of the immune system that can recognize organisms that invade the
body (such as bacteria, viruses, and fungi). The
antibodies are then able to set off a complex chain
of events designed to kill these foreign invaders.
Antigens—Markers on the outside of bacteria or
viruses which can be recognized by antibodies.
Bioterrorism—The use of disease microorganisms
to intimidate or terrorize a civilian population.
Immune system—The system of specialized
organs, lymph nodes, and blood cells throughout
the body which work together to prevent foreign
invaders (bacteria, viruses, fungi, etc.) from taking
hold and growing.

Minocycline Treatment in Japanese Patients with
Coxiella burnetii Infection Considered to Have Post-Q
Fever Fatigue Syndrome.’’ Internal Medicine 43
(January 2004): 1–2.
Gami, A. S., V. S. Antonios, R. L. Thompson, et al. ‘‘Q
Fever Endocarditis in the United States.’’ Mayo Clinic
Proceedings 79 (February 2004): 253–257.
Madariaga, M. G., J. Pulvirenti, M. Sekosan, et al. ‘‘Q Fever
Endocarditis in HIV-Infected Patient.’’ Emerging
Infectious Diseases 10 (March 2004): 501–504.
Wortmann, G. ‘‘Pulmonary Manifestations of Other
Agents: Brucella, Q Fever, Tularemia and Smallpox.’’
Respiratory Care Clinics of North America 10
(March 2004): 99–109.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Inflammation—The body’s response to tissue
damage. Includes increased heat, swelling, redness,
and pain in the affected part.

will require surgery to replace their damaged heart
valves.

Prevention
Q fever can be prevented by the appropriate handling of potentially infective substances. For example,
milk should always be pasteurized, and people who
work with animals giving birth should carefully dispose of the tissues and fluids associated with birth.
Industries which process animal materials (meat,
wool) should take care to prevent the contamination
of dust within the plant.
Vaccines are available for workers at risk for Q
fever.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Biological Warfare and Terrorism.’’ In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors. ‘‘Q
Fever.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Arashima, Y., K. Kato, T. Komiya, et al. ‘‘Improvement of
Chronic Nonspecific Symptoms by Long-Term
3122

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

Qigong
Definition
Qigong (pronounced ‘‘chee-gung,’’ also spelled
chi kung) is translated from the Chinese to mean
‘‘energy cultivation’’ or ‘‘working with the life
energy.’’ Qigong is an ancient Chinese system of
postures, exercises, breathing techniques, and meditations. Its techniques are designed to improve and
enhance the body’s qi. According to traditional
Chinese philosophy, qi is the fundamental life energy
responsible for health and vitality.

Purpose
Qigong may be used as a daily routine to increase
overall health and well-being, as well as for disease
prevention and longevity. It can be used to increase
energy and reduce stress. In China, qigong is used in
conjunction with other medical therapies for many
chronic conditions, including asthma, allergies,
AIDS, cancer, headaches, hypertension, depression,
mental illness, strokes, heart disease, and obesity.
Qigong is presently being used in Hong Kong to
relieve depression and improve the overall psychological and social well-being of elderly people with
chronic physical illnesses.
GALE ENCYCLOPEDIA OF MEDICINE

Origins
Qigong originated before recorded history.
Scholars estimate qigong to be as old as 5,000–7,000
years old. Tracing the exact historical development of
qigong is difficult, because it was passed down in
secrecy among monks and teachers for many generations. Qigong survived through many years before
paper was invented, and it also survived the Cultural
Revolutions in China of the 1960s and 1970s, which
banned many traditional practices.
Qigong has influenced and been influenced by
many of the major strands of Chinese philosophy.
The Taoist philosophy states that the universe operates within laws of balance and harmony, and that
people must live within the rhythms of nature—ideas
that pervade qigong. When Buddhism was brought
from India to China around the seventh century A.D.,
yoga techniques and concepts of mental and spiritual
awareness were introduced to qigong masters. The
Confucian school was concerned with how people
should live their daily lives, a concern of qigong as
well. The martial arts were highly influenced by
qigong, and many of them, such as t’ai chi and kung
fu, developed directly from it. Traditional Chinese
medicine also shares many of the central concepts of
qigong, such as the patterns of energy flow in the
body. Acupuncture and acupressure use the same
points on the body that qigong seeks to stimulate. In
China, qigong masters have been renowned physicians
and healers. Qigong is often prescribed by Chinese
physicians as part of the treatment.
Due to the political isolation of China, many
Chinese concepts have been shrouded from the
Western world. Acupuncture was ‘‘discovered’’ by
American doctors only in the 1970s, although it had
been in use for thousands of years. With an increased
exchange of information, more Americans have gained
access to the once-secret teachings of qigong. In 1988,
the First World Conference for Academic Exchange
of Medical Qigong was held in Beijing, China, where
many studies were presented to attendees from around
the world. In 1990, Berkeley, California, hosted the
First International Congress of Qigong. In the past
decade, more Americans have begun to discover the
beneficial effects of qigong, which motivate an
estimated 60 million Chinese to practice it every day.
Basic concepts
In Chinese thought, qi, or chi, is the fundamental
life energy of the universe. It is invisible but present in
GALE ENCYCLOPEDIA OF MEDICINE

air, water, food and sunlight. In the body, qi is the
unseen vital force that sustains life. We are all born
with inherited amounts of qi, and we also get acquired
qi from the food we eat and the air we breathe. In
qigong, the breath is believed to account for the largest
quantity of acquired qi, because the body uses air
more than any other substance. The balance of our
physical, mental, and emotional levels also affect qi
levels in the body.
Qi travels through the body along channels called
meridians. There are 12 main meridians, corresponding to the 12 principal organs as defined by the
traditional Chinese system: the lung, large intestines,
stomach, spleen, heart, small intestine, urinary bladder, kidney, liver, gallbladder, pericardium, and the
‘‘triple warmer,’’ which represents the entire torso
region. Each organ has qi associated with it, and
each organ interacts with particular emotions on the
mental level. Qigong techniques are designed to
improve the balance and flow of energy throughout
the meridians, and to increase the overall quantity
and volume of qi. In qigong philosophy, mind and
body are not separated as they often are in Western
medicine. In qigong, the mind is present in all parts of
the body, and the mind can be used to move qi
throughout the body.
Yin and yang are also important concepts in
qigong. The universe and the body can be described
by these two separate but complementary principles,
which are always interacting, opposing, and influencing each other. One goal of qigong is to balance
yin and yang within the body. Strong movements or
techniques are balanced by soft ones, leftward movements by rightward, internal techniques by external
ones, and so on.
Practicing qigong
There are thousands of qigong exercises. The specific ones used may vary depending on the teacher,
school, and objective of the practitioner. Qigong is
used for physical fitness, as a martial art, and most
frequently for health and healing. Internal qigong is
performed by those wishing to increase their own
energy and health. Some qigong masters are renowned
for being able to perform external qigong, by which
the energy from one person is passed on to another for
healing. This transfer may sound suspect to Western
logic, but in the world of qigong there are some amazing accounts of healing and extraordinary capabilities
demonstrated by qigong masters. Qigong masters generally have deep knowledge of the concepts of Chinese
medicine and healing. In China, there are hospitals
that use medical qigong to heal patients, along with
3123

Qigong

Description

Qigong

herbs, acupuncture, and other techniques. In these
hospitals, qigong healers use external qigong and
also design specific internal qigong exercises for
patients’ problems.
There are basic components of internal qigong
sessions. All sessions require warm-up and concluding
exercises. Qigong consists of postures, movements,
breathing techniques, and mental exercises. Postures
may involve standing, sitting, or lying down.
Movements include stretches, slow motions, quick
thrusts, jumping, and bending. Postures and movements are designed to strengthen, stretch, and tone
the body to improve the flow of energy. One sequence
of postures and movements is known as the ‘‘Eight
Figures for Every Day.’’ This sequence is designed to
quickly and effectively work the entire body, and is
commonly performed daily by millions in China.
Breathing techniques include deep abdominal
breathing, chest breathing, relaxed breathing, and
holding breaths. One breathing technique is called the
‘‘Six Healing Sounds.’’ This technique uses particular
breathing sounds for each of six major organs. These
sounds are believed to stimulate and heal the organs.
Meditations and mind exercises are used to
enhance the mind and move qi throughout the body.
These exercises are often visualizations that focus on
different body parts, words, ideas, objects, or energy
flowing along the meridians. One mental exercise is
called the ‘‘Inner Smile,’’ during which the practitioner
visualizes joyful, healing energy being sent sequentially
to each organ in the body. Another mental exercise is
called the ‘‘Microscopic Orbit Meditation,’’ in which
the practitioner intently meditates on increasing and
connecting the flow of qi throughout major channels.
Discipline is an important dimension of qigong.
Exercises are meant to be performed every morning
and evening. Sessions can take from 15 minutes to
hours. Beginners are recommended to practice between
15–30 minutes twice a day. Beginners may take classes
once or twice per week, with practice outside of class.
Classes generally cost between $10–$20 per session.

Preparations
Qigong should be practiced in a clean, pleasant
environment, preferably outdoors in fresh air. Loose
and comfortable clothing is recommended. Jewelry
should be removed. Practitioners can prepare for
success at qigong by practicing at regular hours each
day to promote discipline. Qigong teachers also
recommend that students prepare by adopting lifestyles that promote balance, moderation, proper rest,
3124

and healthy diets, all of which are facets of qigong
practice.

Precautions
Beginners should learn from an experienced teacher, as performing qigong exercises in the wrong
manner may cause harm. Practitioners should not perform qigong on either full or completely empty stomachs. Qigong should not be performed during
extreme weather, which may have negative effects on
the body’s energy systems. Menstruating and pregnant
women should perform only certain exercises.

Side effects
Side effects may occur during or after qigong exercises for beginners, or for those performing exercises
incorrectly. Side effects may include dizziness, dry
mouth, fatigue, headaches, insomnia, rapid heartbeat,
shortness of breath, heaviness or numbness in areas of
the body, emotional instability, anxiety, or decreased
concentration. Side effects generally clear up with rest
and instruction from a knowledgeable teacher.

Research and general acceptance
Western medicine generally does not endorse any
of the traditional Chinese healing systems that utilize
the concept of energy flow in the body, largely
because this energy has yet to be isolated and measured scientifically. New research is being conducted
using sophisticated equipment that may verify the
existence of energy channels as defined by the
Chinese system. Despite the lack of scientific validation, the results of energy techniques including
qigong and acupuncture have gained widespread
interest and respect. One California group of qigong
practitioners now conducts twice-yearly retreats to
improve their skills and energy level. Furthermore,
qigong masters have demonstrated to Western observers astounding control over many physical functions, and some have even shown the ability to
increase electrical voltage measured on their skin’s
surface. Most of the research and documentation of
qigong’s effectiveness for medical conditions has
been conducted in China, and is slowly becoming
more available to English readers. Papers from the
World Conferences for Academic Exchange of
Medical Qigong are available in English, and address
many medical studies and uses of qigong. A video is
now available that presents the basic concepts of
medical qigong as well as specific exercise prescriptions for the treatment of breast cancer. The exercise
GALE ENCYCLOPEDIA OF MEDICINE

Martial arts—Group of diverse activities originating from the ancient fighting techniques of the
Orient.
Meridians—Channels or conduits through which
Qi travels in the body.
Qi—Basic life energy, according to traditional
Chinese medicine.
Yin/Yang—Universal characteristics used to
describe aspects of the natural world.

prescriptions consist of movements, postures, visualizations, and positive affirmations.
In terms of mainstream research in the United
States, the first ongoing long-term study of qigong
began in 1999 at the Center for Alternative and
Complementary Medicine Research in Heart Disease
at the University of Michigan; it focuses on the speed of
healing of graft wounds in patients undergoing
coronary bypass surgery. The National Center for
Complementary and Alternative Medicine (NCCAM)
has been funding studies of qigong since 2000. The first
such study was conducted by a researcher in Arizona
with patients using heart devices (pacemakers, etc.).
The breathing techniques of qigong are being
studied intensively by Western physicians as of 2003 as
a form of therapy for anxiety-related problems and for
disorders involving the vocal cords. Qigong is also being
used in the rehabilitation of patients with severe asthma
or chronic obstructive pulmonary disease (COPD).

Training and certification
In China, qigong has been subject to much government regulation, from banning to increased
requirements for teachers. In the United States at
this time, qigong has not been regulated. Different
schools may provide teacher training, but there are
no generally accepted training standards. Qigong
teachings may vary, depending on the founder of the
school, who is often an acknowledged Chinese master.
The organizations listed below can provide further
information to consumers.
Resources
BOOKS

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I: Sound Mind, Sound Body: Qi Gong. New York:
Simon & Schuster, 2002.
GALE ENCYCLOPEDIA OF MEDICINE

Baker, S. E., C. M. Sapienza, and S. Collins. ‘‘Inspiratory
Pressure Threshold Training in a Case of Congenital
Bilateral Abductor Vocal Fold Paralysis.’’ International
Journal of Pediatric Otorhinolaryngology 67 (April
2003): 413–416.
Biggs, Q. M., K. S. Kelly, and J. D. Toney. ‘‘The Effects of
Deep Diaphragmatic Breathing and Focused Attention
on Dental Anxiety in a Private Practice Setting.’’ Dental
Hygiene 77 (Spring 2003): 105–113.
Emerich, K. A. ‘‘Nontraditional Tools Helpful in the
Treatment of Certain Types of Voice Disturbances.’’
Current Opinion in Otolaryngology and Head and Neck
Surgery 11 (June 2003): 149–153.
Golden, Jane. ‘‘Qigong and Tai Chi as Energy Medicine.’’
Share Guide (November-December 2001): 37.
Johnson, Jerry Alan. ‘‘Medical Qigong for Breast Disease.’’
Share Guide (November-December 2001): 109.
Ram, F. S., E. A. Holloway, and P. W. Jones. ‘‘Breathing
Retraining for Asthma.’’ Respiratory Medicine 97 (May
2003): 501–507.
Tsang, H. W., C. K. Mok, Y. T. Au Yeung, and
S. Y. Chan. ‘‘The Effect of Qigong on General
and Psychosocial Health of Elderly with Chronic
Physical Illnesses: A Randomized Clinical Trial.’’
International Journal of Geriatric Psychiatry 18
(May 2003): 441–449.
ORGANIZATIONS

Chinese National Chi Kung Institute. PO Box 31578. San
Francisco, CA 94131. (800) 824-2433.
International Chi Kung/Qi Gong Directory. 2730 29th
Street. Boulder, CO 80301. (303) 442-3131.
National Center for Complementary and Alternative
Medicine (NCCAM) Clearinghouse. P.O. Box 7923,
Gaithersburg, MD 20898-7923. (888) 644-6226.
<http://nccam.nih.gov>.
Qigong Human Life Research Foundation. PO Box 5327.
Cleveland, OH 44101. (216) 475-4712.
OTHER

Qigong Magazine. PO Box 31578. San Francisco, CA 94131.
(800) 824-2433.
Qi: The Journal of Traditional Eastern Health and
Fitness. PO Box 221343. Chantilly, VA 22022. (202)
378 3859.

Douglas Dupler, MA
Rebecca J. Frey, PhD

Quadriplegia see Paralysis
Quarantine see Isolation
Quinidine see Antiarrhythmic drugs
Quinine see Antimalarial drugs
3125

Qigong

PERIODICALS

KEY TERMS

R
Rabbit fever see Tularemia

Rabies
Definition
Rabies is an acute viral disease of the central
nervous system that affects humans and other mammals
but is most common in carnivores (flesh-eaters). It is
sometimes referred to as a zoonosis, or disease of animals
that can be communicated to humans. Rabies is almost
exclusively transmitted through saliva from the bite of
an infected animal. Another name for the disease is
hydrophobia, which literally means ‘‘fear of water,’’ a
symptom shared by half of all people infected with
rabies. Other symptoms include fever, depression,
confusion, painful muscle spasms, sensitivity to touch,
loud noise, and light, extreme thirst, painful swallowing,
excessive salivation, and loss of muscle tone. If rabies is
not prevented by immunization, it is almost always fatal.

Description
Cases of rabies in humans are very infrequent in
the United States and Canada, averaging one or two a
year (down from over 100 cases annually in 1900), but
the worldwide incidence is estimated to be between
30,000 and 50,000 cases each year. These figures
are based on data collected by the World Health
Organization (WHO) in 1997 and updated in 2002.
Rabies is most common in developing countries in
Africa, Latin America, and Asia, particularly India.
Dog bites are the major origin of infection for humans
in developing countries, but other important host animals may include the wolf, mongoose, raccoon, jackal,
and bat. A group of researchers in India found that
monkeys as well as dogs were frequent vectors of
rabies. The team also reported that the male:female
ratio of rabies patients in India is 4:1.
GALE ENCYCLOPEDIA OF MEDICINE

Most deaths from rabies in the United States and
Canada result from bat bites; the most recent fatality
was a 66-year-old man in California who died in
September 2003. The death of a nine-year-old girl in
Quebec in the fall of 2000 was the first case of human
rabies in Canada since 1985. Public health officials
eventually determined that the girl had been bitten
while she was sleeping by a silver-haired bat that had
gotten into the family’s home.
On October 18, 2004, a Wisconsin teenager was
diagnosed with full-blown rabies after suffering
from a minor bat bite on September 12, 2004.
Miraculously, she was cured of rabies after doctors
induced coma and administered four antiviral drugs
to her. Since the therapy was only given and successful for one case, its curative properties needs to be
corroborated by other cases before it will be considered a viable treatment option. The case and the
physicians’ findings will be published in a medical
journal.
People whose work frequently brings them in
contact with animals are considered to be at higher
risk than the general population. This would include
those in the fields of veterinary medicine, animal
control, wildlife work, and laboratory work involving live rabies virus. People in these occupations and
residents of or travelers to areas where rabies is a
widespread problem should consider being
immunized.
In late 2002, rabies re-emerged as an important
public health issue. Dr. Charles E. Rupprecht, director
of the World Health Organization (WHO) Collaborating Center for Rabies Reference and Research, has
listed several factors responsible for the increase in the
number of rabies cases worldwide:


Rapid evolution of the rabies virus. Bats in the
United States have developed a particularly infectious form of the virus.



Increased diversity of animal hosts for the disease.
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Rabies



Changes in the environment that are bringing people
and domestic pets into closer contact with infected
wildlife.



Increased movement of people and animals across
international borders. In one recent case, a man who
had contracted rabies in the Philippines was not
diagnosed until he began to feel ill in the United
Kingdom.



Lack of advocacy about rabies.

Causes and symptoms
Rabies is caused by a rod- or bullet-shaped virus
that belongs to the family Rhabdoviridae. The rabies
virus is a member of a genus of viruses called lyssaviruses, which include several related viruses that
infect insects as well as mammals. The rabies virus is
usually transmitted via an animal bite, however, cases
have also been reported in which the virus penetrated
the body through infected saliva, moist tissues such as
the eyes or lips, a scratch on the skin, or the transplantation of infected tissues. Inhalation of the virus in
the air, as might occur in a highly populated bat cave,
is also thought to occur.
From the bite or other area of penetration, the
virus multiplies as it spreads along nerves that travel
away from the spinal cord and brain (efferent nerves)
and into the salivary glands. The rabies virus may
lie dormant in the body for several weeks or months,
but rarely much longer, before symptoms appear.
Initially, the area around the bite may burn and be
painful. Early symptoms may also include a sore
throat, low-grade fever, headache, loss of appetite,
nausea and vomiting, and diarrhea. Painful spasms
develop in the muscles that control breathing and
swallowing. The individual may begin to drool thick
saliva and may have dilated or irregular pupils,
increased tears and perspiration, and low blood
pressure.
Later, as the disease progresses, the patient
becomes agitated and combative and may exhibit
increased mental confusion. The affected person
usually becomes sensitive to touch, loud noises, and
bright lights. The victim also becomes extremely
thirsty, but is unable to drink because swallowing is
painful. Some patients begin to dread water because
of the painful spasms that occur. Other severe symptoms during the later stage of the disease include
excessive salivation, dehydration, and loss of muscle
tone. Death usually occurs three to 20 days after
symptoms have developed. Unfortunately, recovery
is very rare.
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Diagnosis
After the onset of symptoms, blood tests and
cerebrospinal fluid (CSF) analysis tests will be conducted. CSF will be collected during a procedure
called a lumbar puncture in which a needle is used to
withdraw a sample of CSF from the area around the
spinal cord. The CSF tests do not confirm diagnosis
but are useful in ruling out other potential causes for
the patient’s altered mental state.
The two most common diagnostic tests are the
fluorescent antibody test and isolation of the rabies
virus from an individual’s saliva or throat culture. The
fluorescent antibody test involves taking a small
sample of skin (biopsy) from the back of the neck of
the patient. If specific proteins, called antibodies, that
are produced only in response to the rabies virus
are present, they will bind with the fluorescent dye
and become visible. Another diagnostic procedure
involves taking a corneal impression in which a swab
or slide is pressed lightly against the cornea of the eye
to determine whether viral material is present.

Treatment
Until the most recent successful cure of a late-term
rabies case can be validated with further success and
validation from the medical community, the historic
treatment options for rabies prevention immediately
following a bite remains the most viable treatment.
Because of the extremely serious nature of a rabies
infection, the need for rabies immunizations will be
carefully considered for anyone who has been bitten
by an animal, based on a personal history and results
of diagnostic tests.
If necessary, treatment includes the following:


The wound is washed thoroughly with medicinal
soap and water. Deep puncture wounds should be
flushed with a catheter and soapy water. Unless
absolutely necessary, a wound should not be sutured.



Tetanus toxoid and antibiotics will usually be
administered.



Rabies vaccination may or not be given, based on the
available information. If the individual was bitten by
a domestic animal and the animal was captured, the
animal will be placed under observation in quarantine for ten days. If the animal does not develop
rabies within four to seven days, then no immunizations are required. If the animal is suspected of being
rabid, it is killed, and the brain is examined for
evidence of rabies infection. In cases involving bites
from domestic animals where the animal is not available for examination, the decision for vaccination is
GALE ENCYCLOPEDIA OF MEDICINE



If necessary, the patient is vaccinated immediately,
generally through the administration of human rabies
immune globulin (HRIG) for passive immunization,
followed by human diploid cell vaccine (HDCV) or
rabies vaccine adsorbed (RVA) for active immunization. Passive immunization is designed to provide the
individual with antibodies from an already immunized individual, while active immunization involves
stimulating the individual’s own immune system to
produce antibodies against the rabies virus. Both
rabies vaccines are equally effective and carry a
lower risk of side effects than some earlier treatments.
Unfortunately, however, in underdeveloped countries, these newer vaccines are usually not available.
Antibodies are administered to the patient in a process
called passive immunization. To do this, the HRIG
vaccine is administered once, at the beginning of treatment. Half of the dose is given around the bite area,
and the rest is given in the muscle. Inactivated viral
material (antigenic) is then given to stimulate the
patient’s own immune system to produce antibodies
against rabies. For active immunization, either the
HDCV or RVA vaccine is given in a series of five
injections. Immunizations are typically given on days
one, three, seven, 14, and 28.

In those rare instances in which rabies has progressed beyond the point where immunization would
be effective, the groundbreaking treatment involving a
drug-induced coma and the administration of four
different antiviral drugs will most likely be a radical
treatment option. The traditional approach prior to
October 2004 was to provide as much relief from pain
and suffering as possible through medical intervention
while waiting to see if survival was possible. The
patient would be given medication to prevent seizures,
relieve some of the anxiety, and relieve painful muscle
spasms. Pain relievers would also be given. In the later
stages, aggressive supportive care would be provided
to maintain breathing and heart function. Survival via
the traditional treatment is rare but can occur.

Prognosis
If preventative treatment is sought promptly,
rabies need not be fatal. Immunization is almost
always effective if started within two days of the bite.
Chance of effectiveness declines, however, the longer
vaccination is put off. It is, however, important to start
GALE ENCYCLOPEDIA OF MEDICINE

Rabies

made based on the prevalence of rabies within the
region where the bite occurred. If the bite was from
a wild animal and the animal was captured, it is
generally killed because the incubation period of
rabies is unknown in most wild animals.

KEY TERMS
Active immunization—Treatment that provides
immunity by challenging an individual’s own
immune system to produce antibody against a
particular organism, in this case the rabies virus.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Biopsy—The removal of a small sample of tissue for
diagnostic purposes.
Efferent nerves—Nerves that convey impulses
away from the central nervous system to the
periphery.
Fluorescent antibody test (FA test)—A test in
which a fluorescent dye is linked to an antibody
for diagnostic purposes.
Lumbar puncture—A procedure that involves
withdrawing a small sample of cerebrospinal fluid
from the back around the spinal cord.
Lyssavirus—A genus of viruses that includes the
rabies virus and related viruses that infect insects
as well as mammals.
Passive immunization—Treatment that provides
immunity through the transfer of antibodies obtained
from an immune individual.
Rhabdovirus—A type of virus named for its rod- or
bullet-like shape. The rabies virus belongs to a
family of viruses called Rhabdoviridae.
Vector—An animal or insect that carries a diseaseproducing organism.
Zoonosis—Any disease of animals that can be
transmitted to humans. Rabies is an example of a
zoonosis.

immunizations, even if it has been weeks or months
following a suspected rabid animal bite, because the
vaccine can be effective even in these cases. If immunizations do not prove effective or are not received,
rabies is nearly always fatal with a few days of the
onset of symptoms.
As of October 2004, the medical community
awaits the publication of findings by the doctors that
administered a life-saving treatment that cured a
Wisconsin teenager of full-blown rabies. Further test
cases will prove whether or not this treatment option
will be a historic development in the search for a cure
for rabies.
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Rabies

Prevention
One promising preventive strategy that has been
used since the early 2000s is the distribution of wildlife
baits containing an oral vaccine against rabies. This
strategy has been used in Germany to vaccinate wild
foxes, which are frequent carriers of the disease in
Europe. In the United States, veterinary researchers
at Kansas State University have developed an oral
vaccine for fruit bats; early trials of the vaccine have
given promising results.
The following precautions should be observed in
environments where humans and animals may likely
come into contact.


Domesticated animals, including household pets,
should be vaccinated against rabies. If a pet is bitten
by an animal suspected to have rabies, its owner should
contact a veterinarian immediately and notify the
local animal control authorities. Domestic pets with
current vaccinations should be revaccinated immediately; unvaccinated dogs, cats, or ferrets are usually
euthanized (put to sleep). Further information about
domestic pets and rabies is available on the American
Veterinary Medical Association (AVMA) web site.



Wild animals should not be touched or petted, no
matter how friendly they may appear. It is also
important not to touch an animal that appears ill or
passive, or whose behavior seems odd, such as failing
to show the normal fear of humans. These are all
possible signs of rabies. Many animals, such as
raccoons and skunks, are nocturnal and their activity
during the day should be regarded as suspicious.



People should not interfere in fights between
animals.



Because rabies is transmitted through saliva, a
person should wear rubber gloves when handling
a pet that has had an encounter with a wild animal.



Garbage or pet food should not be left outside the
house or camp site because it may attract wild or
stray animals.



Windows and doors should be screened. Some victims
of rabies have been attacked by infected animals,
particularly bats, that entered through unprotected
openings.



State or county health departments should be
consulted for information about the prevalence of
rabies in an area. Some areas, such as New York
City, have been rabies-free, only to have the disease
reintroduced at a later time.



Preventative vaccination against rabies should be
considered if one’s occupation involves frequent

3130

contact with wild animals or non-immunized domestic animals.


Bites from mice, rats, or squirrels rarely require
rabies prevention because these rodents are typically
killed by any encounter with a larger, rabid animal,
and would, therefore, not be carriers.



Travelers should ask about the prevalence of the
disease in countries they plan to visit.

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Central Nervous System Viral Diseases: Rabies
(Hydrophobia).’’ Section 13, Chapter 162 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PERIODICALS

Chhabra, M., R. L. Ichhpujani, K. N. Tewari, and S. Lal.
‘‘Human Rabies in Delhi.’’ Indian Journal of Pediatrics
71 (March 2004): 217–220.
Deshaies, D., P. A. Pilon, L. Valiquette, and J. Carsley.
‘‘A Public Health Intervention at the Time of a Case of
Rabies in Quebec.’’ [in French] Canadian Journal of
Public Health 95 (March-April 2004): 138–141.
Fooks, A. R., N. Johnson, S. M. Brookes, et al. ‘‘Risk
Factors Associated with Travel to Rabies Endemic
Countries.’’ Journal of Applied Microbiology 94,
Supplement (2003): 31S–36S.
‘‘Human Death Associated with Bat Rabies—California,
2003.’’ Morbidity and Mortality Weekly Report 53
(January 23, 2004): 33–35.
Messenger, S. L., J. S. Smith, L. A. Orciari, et al. ‘‘Emerging
Pattern of Rabies Deaths and Increased Viral
Infectivity.’’ Emerging Infectious Diseases 9 (February
2003): 151–154.
Peters, C., R. Isaza, D. J. Heard, et al. ‘‘Vaccination of
Egyptian Fruit Bats (Rousettus aegyptiacus) with
Monovalent Inactivated Rabies Vaccine.’’ Journal of
Zoo and Wildlife Medicine 35 (March 2004): 55–59.
Rosenthal, Elisabeth. ‘‘Girl is first to survive rabies without
a shot.’’ The New York Times November 25, 2004: A28.
Smith, J., L. McElhinney, G. Parsons, et al. ‘‘Case Report:
Rapid Ante-Mortem Diagnosis of a Human Case of
Rabies Imported Into the UK from the Philippines.’’
Journal of Medical Virology 69 (January 2003): 150–155.
Stringer, C. ‘‘Post-Exposure Rabies Vaccination.’’ Nursing
Standard 17 (February 5-11, 2003): 41–42.
Thulke, H. H., T. Selhorst, T. Muller, et al. ‘‘Assessing
Anti-Rabies Baiting—What Happens on the Ground?’’
BMC Infectious Diseases 4 (March 9, 2004): 9.
Weiss, R. A. ‘‘Cross-Species Infections.’’ Current Topics in
Microbiology and Immunology 278 (2003): 47–71.
ORGANIZATIONS

American Veterinary Medical Association (AVMA). 1931
North Meacham Road, Suite 100, Schaumburg, IL
60173-4360. <http://www.avma.org>.
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OTHER

CDC. ‘‘Epidemiology of Rabies.’’ <http://www.cdc.gov/
ncidod/dvrd/rabies/Epidemiology/
Epidemiology.htm>.
National Association of State Public Health Veterinarians,
Inc. ‘‘Compendium of Animal Rabies Prevention and
Control, 2003.’’ Morbidity and Mortality Weekly
Report Recommendations and Reports 52
(March 21, 2003) (RR-5): 1–6.

Janet Byron Anderson
Rebecca J. Frey, PhD

Radial keratotomy
Definition
Radial keratotomy (RK) is a type of eye surgery
used to correct myopia (nearsightedness). It works by
changing the shape of the cornea–the transparent part
of the eye that covers the iris and the pupil.

Purpose
About 25–30% of all people in the world are
nearsighted and need eyeglasses or contact lenses for
distance vision to be clear. For a number of reasons,
some people don’t like wearing corrective lenses. Some
feel unattractive in eyeglasses. Others worry about not
being able to see without their glasses in an emergency,
such as a house fire or a burglary. Both glasses and
contact lenses can be scratched, broken, or lost. In
addition, contact lenses require special care and can
irritate the eyes.
Radial keratotomy was introduced in North
America in 1978. Since then doctors have improved
the technique, and its results have become more predictable. Radial keratotomy is one of several surgical
techniques to correct nearsightedness, reducing or
eliminating the need for corrective lenses. It is most
successful in patients with a low to moderate amount
of nearsightedness–people whose eyes require up to -5.00
diopters of correction. A diopter (D) is a unit of
measure of focusing power. Minus lenses correct
nearsightedness.
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Precautions
Not every nearsighted person is a good candidate
for radial keratotomy. This type of surgery cannot
help people whose nearsightedness is caused by keratoconus, a rare condition in which the cornea is cone
shaped. The procedure usually is not done on patients
under 18, because their eyes are still growing and
changing shape. It is important that visual status is
stable. Women who are pregnant, have just given
birth, or are breast-feeding should not have the
surgery because hormonal changes may cause temporary changes in the cornea. In addition, anyone with
glaucoma or with any disease that interferes with healing (e.g., rheumatoid arthritis, lupus erythematosus, or
uncontrolled diabetes) should not have RK.
Radial keratotomy weakens the cornea, making it
vulnerable to injuries even long after the surgery.
Getting hit in the head after having RK can cause
the cornea to tear and can lead to blindness. For this
reason, the procedure is not recommended for people
who engage in sports that could result in a blow to the
head (i.e., karate or racquetball).
It is important to keep in mind that RK is a
permanent procedure and that success cannot be guaranteed. An experienced eye surgeon can estimate how
likely it is that the surgery will help a particular
patient, but that is just an estimate. There is no way
to know for sure whether the surgery will improve
eyesight enough to eliminate the need for corrective
lenses. Vision usually improves after RK, but it is not
always perfect. Anyone who decides to have RK
should be prepared to accept less-than-perfect vision
after surgery, which may necessitate the continued use
of glasses or contact lenses. This surgery does not
eliminate the need for reading glasses. Actually, someone who didn’t need reading glasses before surgery
because their myopia allowed near vision to be clear
may find themselves needing reading glasses. Patients
must ask about this prior to surgery.
Anyone considering RK should also be aware that
certain professions, including branches of the military,
are not open to people who have had the procedure.
A reputable ophthalmologist will discuss the risks
of the procedure and should tell anyone considering it
that perfect vision can’t be guaranteed. Patients
should be wary of any doctor who tries too hard to
‘‘sell’’ them on RK.

Description
In a person with clear vision, light passes through
the cornea and the lens of the eye and focuses on a
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Radial keratotomy

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
Institut Pasteur. 25-28, rue du Dr. Roux, 75015 Paris,
France. +33 (0) 1 45 68 80 00. <http://
www.pasteur.fr/haut_ext.html>.

Radial keratotomy
Radial keratotomy scars on the cornea of an eye. (Photograph by Bob Masini, Phototake NYC. Reproduced by permission.)

membrane lining the back of the eye called the retina.
In a person with myopia, the eyeball is usually too
long, so light focuses in front of the retina. Radial
keratotomy reduces myopia by flattening the cornea.
This reduces the focusing power of the cornea allowing light to focus further back onto the retina (or at
least closer to it), forming a clearer image.
A surgeon performing RK uses a very small diamond-blade knife to makes four to eight radial incisions around the edge of the cornea. These slits are
made in a pattern that resembles the spokes of wheel.
As the cornea heals, its center flattens out.
Radial keratotomy is usually performed in an
ophthalmologist’s office. Before the surgery begins,
the patient may be given medicine to help him or her
relax. A local anesthetic–usually in the form of eye
drops–is used to numb the eye, but the patient remains
conscious during the procedure. The surgeon looks
through a surgical microscope while making the slits.
The treatment usually takes no more than 30 minutes.
Some ophthalmologists will perform RK on both
eyes at once but others prefer to do one eye at a time. It
once was thought that surgeons could use the results of
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the first eye to predict how the well the procedure
would work on the second eye. However, a study
published in 1997 found that this was not the case.
The authors of the study cautioned that there might be
other reasons not to operate on both eyes at once, such
as increased risk of infection and other complications.
The cost for RK depends on the surgeon, but
usually ranges from $1,000–$1,500 per eye. Medical
insurance usually does not cover RK, because it is
considered an elective procedure–one that people
choose to have done.

Preparation
Before beginning the procedure, the surgeon
marks an area in the center of the cornea called the
optical zone. This is the part of the cornea that one sees
through (it is the area over the pupil). No cuts are made
in this region. The surgeon also measures the cornea’s
thickness, to decide how deep the slits should be.

Aftercare
After the surgery is over, the anesthetic wears off.
Some patients feel slight pain and are given eye drops
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cornea—The transparent part of the eye that covers
the iris and the pupil.
Diopter (D)—Unit describing the amount of focusing power of a lens.

As with any type of surgery, it is important to
guard against infection. Patients are given eye drops
to protect against infection and may be told to use
them for several weeks after the surgery. Because RK
weakens the cornea it is important to protect the head
and eyes.

Iris—The colored part of the eye.
Laser-assisted in situ keratomileusis (LASIK)—A
type of refractive eye surgery using a laser and
another instrument to change the shape of the
cornea.

The cornea heals slowly, and full recovery can
take several months (another reason not to have the
surgery done on both eyes at the same time). While the
cornea is healing, patients may experience these
problems:


Variations in vision. Eyesight may be better in the
morning than in the evening or vice versa.



Temporary pain.



Increased glare.



Starburst or halo effects. Rays or rings of light
around lights at night.



Hyperopic shift. As the cornea flattens, vision may
become more farsighted (hyperopic). For this reason,
the surgeon may initially undercorrect the patient.
This gradual shift may occur over several years.

If RK does not completely correct a person’s
nearsightedness, glasses or contact lenses may be
needed. In general, people who were able to wear
contact lenses before the procedure can still wear
them afterward. Even patients whose nearsightedness
was corrected may still need glasses for reading. This is
especially true for middle-aged and older patients. The
lens of the eye stiffens with age, making reading glasses
necessary (presbyopia). Radial keratotomy does not
correct this problem.
The surgeon who performs the RK procedure will
tell the patient how often to return for follow-up visits.
Often, two to four visits are needed, including one the
day after surgery. It is also important to know what
side effects should be reported immediately to the
surgeon (e.g., pain or nausea).

Risks
Complications from RK are rare, but they can
occur. These include:


cataract a clouding of the lens of the eye, resulting in
partial or total loss of vision



serious infection



lasting pain

GALE ENCYCLOPEDIA OF MEDICINE

Local anesthetic—Used to numb an area where
surgery or another procedure is to be done, without
causing the patient to lose consciousness.
Myopia—Nearsightedness. People with myopia
cannot see distant objects clearly.
Ophthalmologist—A physician who specializes in
treating eyes.
Photorefractive keratectomy (PRK)—A type of
refractive eye surgery using a laser to change the
shape of the cornea.
Pupil—The part of the eye that looks like a black
circle in the center of the iris. It is actually an opening through which light passes.
Retina—A membrane lining the back of the eye
onto which light is focused to form images.



rips along an incision, especially after being hit in the
head or eye



loss of vision



chance of overcorrection (hyperopic shift)

The chances of complications are reduced when
the surgery is done by an ophthalmologist with a lot of
experience in RK. Younger patients also tend to heal
faster.

Normal results
The desired result of radial keratotomy is a reduction in myopia. A major study by the National Eye
Institute, reported in 1994, tracked the success of RK
in 374 patients who had had the procedure done 10
years earlier. The study found that:


85% had at least 20/40 vision (the acuity considered
good enough to drive without glasses)



70% did not need glasses or contact lenses for distance vision
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Radial keratotomy

and medications to relieve their discomfort. For several days after the surgery, the eye that was treated may
feel scratchy and look red. This is normal. The eye may
also water, burn slightly, and be sensitive to light.

Radiation injuries



53% had 20/20 vision without glasses



30% still needed glasses or contact lenses to see
clearly



1–3% had worse vision than before they had RK



40% had a hyperopic shift.

As with all surgeries, RK has risks. These risks
include having worse vision than before the surgery;
halos; glare; and although rare, blindness. Some
aftereffects, such as halos or glare may last for
years. Other refractive surgeries, such as photorefractive keratectomy (PRK) and laser-assisted in situ
keratomileusis (LASIK) use lasers to change the
shape of the cornea and they may produce fewer
side effects. It is important to speak with an experienced eye surgeon who has done many refractive
surgeries to fully understand the options and risks
involved before making a decision.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100.
<http://www.aoanet.org>.
American Society of Cataract & Refractive Surgery. 4000
Legato Road, Suite 850, Fairfax, VA 22033. (703)
591-2220. <http://www.ascrs.org>.

Nancy Ross-Flanigan

Radiation injuries
Definition
Radiation injuries are caused by ionizing radiation
emitted by sources such as the sun, x-ray and other
diagnostic machines, tanning beds, and radioactive
elements released in nuclear power plant accidents
and detonation of nuclear weapons during war and as
terrorist acts.

Description
Ionizing radiation is made up of unstable atoms
that contain an excess amount of energy. In an attempt
to stabilize, the atoms emit the excess energy into the
atmosphere, creating radiation. Radiation can either
be electromagnetic or particulate.
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The energy of electromagnetic radiation is a direct
function of its frequency. The high–energy, high–frequency waves that can penetrate solids to various
depths cause damage by separating molecules into
electrically charged pieces, a process known as ionization. X rays are a type of electromagnetic radiation.
Atomic particles come from radioactive isotopes as
they decay to stable elements. Electrons are called
beta particles when they radiate. Alpha particles are
the nuclei of helium atoms—two protons and two
neutrons—without the surrounding electrons. Alpha
particles are too large to penetrate a piece of paper
unless they are greatly accelerated in electric and magnetic fields. Both beta and alpha particles are types of
particulate radiation. When over-exposure to ionizing
radiation occurs, there is chromosomal damage in
deoxyribonucleic acid (DNA). DNA is very good at
repairing itself; both strands of the double helix must
be broken to produce genetic damage.
Because radiation is energy, it can be measured.
There are a number of units used to quantify radiation
energy. Some refer to effects on air, others to effects on
living tissue. The roentgen, named after Wilhelm
Conrad Roentgen, who discovered x rays in 1895,
measures ionizing energy in air. A rad expresses the
energy transferred to tissue. The rem measures tissue
response. A roentgen generates about a rad of effect
and produces about a rem of response. The gray and
the sievert are international units equivalent to 100
rads and rems, respectively. A curie, named after
French physicists who experimented with radiation,
is a measure of actual radioactivity given off by a
radioactive element, not a measure of its effect. The
average annual human exposure to natural background radiation is roughly 3 milliSieverts (mSv).
Any amount of ionizing radiation will produce
some damage, however, there is radiation everywhere,
from the sun (cosmic rays) and from traces of radioactive elements in the air (radon) and the ground
(uranium, radium, carbon-14, potassium-40 and
many others). Earth’s atmosphere protects us from
most of the sun’s radiation. Living at 5,000 feet
altitude in Denver, Colorado, doubles exposure to
radiation, and flight in a commercial airliner increases
it 150-fold by lifting us above 80% of that atmosphere.
Because no amount of radiation is perfectly safe and
because radiation is ever present, arbitrary limits have
been established to provide some measure of safety for
those exposed to unusual amounts. Less than 1% of
them reach the current annual permissible maximum
of 20 mSv.
A 2001 ruling by the Federal Court of Australia
indicated that two soldiers died from cancer caused by
GALE ENCYCLOPEDIA OF MEDICINE

Ultraviolet (UV) radiation exposure from the sun
and tanning beds
UV radiation from the sun and tanning beds and
lamps can cause skin damage, premature aging, and
skin cancers. Malignant melanoma is the most dangerous of skin cancers and there is a definite link between
type UVA exposure used in tanning beds and its
occurrence. UVB type UV radiation is associated
with sunburn, and while not as penetrating as UVA,
it still damages the skin with over exposure. Skin
damage accumulates over time, and effects do not
often manifest until individuals reach middle age.
Light-skinned people who most often burn rather
than tan are at a greater risk of skin damage than
darker-skinned individuals that almost never burn.
The U.S. Food and Drug Administration (FDA) and
the Centers for Disease Control (CDC) discourage the
use of tanning beds and sun lamps and encourage the
use of sunscreen with at least an SPF of 15 or greater.
Over exposure during medical procedures
Ionizing radiation has many uses in medicine,
both in diagnosis and in treatment. X rays, CT
scanners, and fluoroscopes use it to form images of
the body’s insides. Nuclear medicine uses radioactive
isotopes to diagnose and to treat medical conditions.
In the body, radioactive elements localize to specific
tissues and give off tiny amounts of radiation.
Detecting that radiation provides information on
both anatomy and function. During the past 10
years, skin injuries caused by too much exposure
during a medical procedure have been documented.
In 1995, the FDA issued a recommendation to physicians and medical institutions to record and monitor
the dosage of radiation used during medical procedures on patients in order to minimize the amount of
skin injuries. The FDA suggested doses of radiation
not exceed 1 Grey (Gy). (A Grey is roughly equivalent
to a sievert.) As of 2001, the FDA was preparing
further guidelines for fluoroscopy, the procedure
most often associated with medical-related radiation
skin injuries such as rashes and more serious burns
and tissue death. Injuries occurred most often during
angioplasty procedures using fluoroscopy.
GALE ENCYCLOPEDIA OF MEDICINE

CT scans of children have also been problematic.
Oftentimes the dosage of radiation used for an adult
isn’t decreased for a child, leading to radiation over
exposure. Children are more sensitive to radiation and
a February 2001 study indicates 1,500 out of 1.6 million
children under 15 years of age receiving CT scans
annually will develop cancer. Studies show that
decreasing the radiation by half for CT scans of
children will effectively decrease the possibility of over
exposure while still providing an effective diagnostic
image. The benefits to receiving the medical treatment
utilizing radiation is still greater than the risks involved,
however, more stringent control over the amount of
radiation used during the procedures will go far to
minimize the risk of radiation injury to the patient.
Radiation exposure from nuclear accidents,
weaponry, and terrorist acts
Between 1945 and 1987, there were 285 nuclear
reactor accidents, injuring over 1,550 people and killing
64. The most striking example was the meltdown of the
graphite core nuclear reactor at Chernobyl in 1986,
which spread a cloud of radioactive particles across
the entire continent of Europe. Information about
radiation effects is still being gathered from that disaster, however 31 people were killed in the immediate
accident and 1,800 children have thus far been
diagnosed with thyroid cancer. In a study published in
May 2001 by the British Royal Society, children born
to individuals involved in the cleanup of Chernobyl
and born after the accident are 600% more likely to
have genetic mutations than children born before the
accident. These findings indicate that exposure to low
doses of radiation can cause inheritable effects.
Since the terrorist attack on the World Trade
Center and the Pentagon on September 11, 2001, the
possibility of terrorist-caused nuclear accidents has
been a growing concern. All 103 active nuclear power
plants in the United States are on full alert, but they
are still vulnerable to sabotage such as bombing or
attack from the air. A no-fly zone of 12 miles below
18,000 feet has been established around nuclear power
plants by the Federal Aviation Administration (FAA).
There is also growing concern over the security of
spent nuclear fuel—more than 40,000 tons of spent
fuel is housed in buildings at closed plants around
the country. Unlike the active nuclear reactors that
are enclosed in concrete-reinforced buildings, the
spent fuel is stored in non-reinforced buildings.
Housed in cooling pools, the spent fuel could emit
dangerous levels of radioactive material if exploded
or used in makeshift weaponry. Radioactive medical
and industrial waste could also be used to make ‘‘dirty
3135

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minimal exposure to radiation while occupying
Hiroshima in 1945. The soldiers were exposed to less
than 5 mSv of radiation. The international recommendation for workers is safety level of up to 20 mSv. The
ruling and its support by many international agencies
suggests that even extremely low doses of radiation
can be potentially harmful.

Radiation injuries

People are affected internally, externally, or with
both internal and external exposure.


Incorporation: dependent on contamination, the
bodies of individuals affected incorporate the radiation chemicals within cells, organs, and tissues and
the radiation is dispersed throughout the body.

Immediately after sudden irradiation, the fate
of those affected depends mostly on the total dose
absorbed. This information comes mostly from survivors of the atomic bomb blasts over Japan in 1945.

This person’s nose is inflamed and scaly due to radiation
exposure. (Custom Medical Stock Photo. Reproduced by
permission.)

bombs.’’ Since 1993, the Nuclear Regulatory
Commission (NRC) has reported 376 cases of stolen
radioactive materials.

Causes and symptoms
Radiation can damage every tissue in the body.
The particular manifestation will depend upon the
amount of radiation, the time over which it is
absorbed, and the susceptibility of the tissue. The
fastest growing tissues are the most vulnerable,
because radiation as much as triples its effects during
the growth phase. Bone marrow cells that make blood
are the fastest growing cells in the body. A fetus in the
womb is equally sensitive. The germinal cells in the
testes and ovaries are only slightly less sensitive. Both
can be rendered useless with very small doses of radiation. More resistant are the lining cells of the body—
skin and intestines. Most resistant are the brain cells,
because they grow the slowest.
The length of exposure makes a big difference in
what happens. Over time the accumulating damage, if
not enough to kill cells outright, distorts their growth
and causes scarring and/or cancers. In addition to
leukemias, cancers of the thyroid, brain, bone, breast,
skin, stomach, and lung all arise after radiation.
Damage depends, too, on the ability of the tissue to
repair itself. Some tissues and some types of damage
produce much greater consequences than others.
There are three types of radiation injuries.


External irradiation: as with x-ray exposure, all or
part of the body is exposed to radiation that either is
absorbed or passes through the body.



Contamination: as with a nuclear accident, the environment and its inhabitants are exposed to radiation.

3136



Massive doses incinerate immediately and are not
distinguishable from the heat of the source.



A sudden whole body dose over 50 Sv produces such
profound neurological, heart, and circulatory
damage that patients die within the first two days.



Doses in the 10–20 Sv range affect the intestines,
stripping their lining and leading to death within
three months from vomiting, diarrhea, starvation,
and infection.



Victims receiving 6–10 Sv all at once usually escape
an intestinal death, facing instead bone marrow failure and death within two months from loss of blood
coagulation factors and the protection against infection provided by white blood cells.



Between 2–6 Sv gives a fighting chance for survival if
victims are supported with blood transfusions and
antibiotics.



One or two Sv produces a brief, non-lethal sickness
with vomiting, loss of appetite, and generalized
discomfort.

Treatment
It is clearly important to have some idea of the
dose received as early as possible, so that attention can
be directed to those victims in the 2–10 Sv range that
might survive with treatment. Blood transfusions, protection from infection in damaged organs, and possibly the use of newer stimulants to blood formation can
save many victims in this category.
Local radiation exposures usually damage the
skin and require careful wound care, removal of dead
tissue, and skin grafting if the area is large. Again
infection control is imperative.
One of the best known, and perhaps even mainstream, treatments of radiation injury is the use of
Aloe vera preparations on damaged areas of skin. It
has demonstrated remarkable healing properties even
for chronic ulcerations resulting from radiation
exposure.
GALE ENCYCLOPEDIA OF MEDICINE

DNA—Deoxyribonucleic acid. The chemical of
chromosomes and hence the vehicle of heredity.
Isotope—An unstable form of an element that gives
off radiation to become stable. Elements are characterized by the number of electrons around each
atom. One electron’s negative charge balances the
positive charge of each proton in the nucleus. To
keep all those positive charges in the nucleus from
repelling each other (like the same poles of magnets), neutrons are added. Only certain numbers of
neutrons work. Other numbers cannot hold the
nucleus together, so it splits apart, giving off ionizing radiation. Sometimes one of the split products is
not stable either, so another split takes place. The
process is called radioactivity.

Alternative treatment
There is considerable interest these days in benevolent chemicals called ‘‘free radical scavengers.’’
How well they work is yet to be determined, but
population studies strongly suggest that certain
diets are better than others, and that those diets are
full of free radical scavengers, otherwise known as
antioxidants. The recommended ingredients are
beta-carotene, vitamins E and C, and selenium, all
available as commercial preparations. Beta-carotene
is yellow-orange and is present in yellow and orange
fruits and vegetables. Vitamin C can be found
naturally in citrus fruits. Traditional Chinese medicine
(TCM) and acupuncture, botanical medicine, and
homeopathy all have contributions to make to recovery from the damage of radiation injuries. The level
of recovery will depend on the exposure. Consulting
practitioners trained in these modalities will result in
the greatest benefit.

Radiation therapy
Definition
Radiation therapy, sometimes called radiotherapy,
x-ray therapy radiation treatment, cobalt therapy,
electron beam therapy, or irradiation uses high energy,
penetrating waves or particles such as x rays, gamma
rays, proton rays, or neutron rays to destroy cancer cells
or keep them from reproducing.

Purpose
The purpose of radiation therapy is to kill or
damage cancer cells. Radiation therapy is a common form of cancer therapy. It is used in more than
half of all cancer cases. Radiation therapy can be
used:


alone to kill cancer



before surgery to shrink a tumor and make it easier
to remove



during surgery to kill cancer cells that may remain in
surrounding tissue after the surgery (called intraoperative radiation)



after surgery to kill cancer cells remaining in the body



to shrink an inoperable tumor in order to and reduce
pain and improve quality of life.



in combination with chemotherapy

For some kinds of cancers such as early-stage
Hodgkin’s disease, non-Hodgkin’s lymphoma, and
certain types of prostate, or brain cancer, radiation
therapy alone may cure the disease. In other cases,
radiation therapy used in conjunction with surgery,
chemotherapy, or both, increases survival rates over
any of these therapies used alone.

Precautions

Resources
PERIODICALS

Grunwald, Michael, and Peter Behr. ‘‘Are Nuclear Plants
Secure? Industry Called Unprepared for Sept. 11-Style
Attack.’’ The Washington Post November 3, 2001, p.
A01.
Vergano, Dan. ‘‘ ‘Dirty’ Bombs Latest Fear.’’ USA Today
November 3, 2001.

Jacqueline L. Longe

Radiation sickness see Radiation injuries
GALE ENCYCLOPEDIA OF MEDICINE

Radiation therapy does not make the person
having the treatments radioactive. In almost all
cases, the benefits of this therapy outweigh the
risks. However radiation therapy can have has serious consequences, so anyone contemplating it
should be sure understand why the treatment team
believes it is the best possible treatment option for
their cancer. Radiation therapy is often not appropriate for pregnant women, because the radiation can
damage the cells of the developing baby. Women who
think they might be pregnant should discuss this with
their doctor.
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Radiation therapy

KEY TERMS

Radiation therapy

Description
Radiation therapy is a local treatment. It is painless. The radiation acts only on the part of the body that
is exposed to the radiation. This is very different from
chemotherapy in which drugs circulate throughout
the whole body. There are two main types of radiation
therapy. In external radiation therapy a beam of radiation is directed from outside the body at the cancer. In
internal radiation therapy, called brachytherapy or
implant therapy, where a source of radioactivity is
surgically placed inside the body near the cancer.
How radiation therapy works
The protein that carries the code controlling most
activities in the cell is called deoxyribonucleic acid or
DNA. When a cell divides, its DNA must also double
and divide. High-energy radiation kills cells by damaging their DNA, thus blocking their ability to grow
and increase in number.
One of the characteristics of cancer cells is that
they grow and divide faster than normal cells. This
makes them particularly vulnerable to radiation.
Radiation also damages normal cells, but because
normal cells are growing more slowly, they are better
able to repair radiation damage than are cancer cells.
In order to give normal cells time to heal and reduce
side effects, radiation treatments are often given in
small doses over a six or seven week period.
External radiation therapy
External radiation therapy is the most common
kind of radiation therapy. It is usually done during
outpatient visits to a hospital clinic and is usually
covered by insurance.
Once a doctor, called a radiation oncologist,
determines the proper dose of radiation for a particular cancer, the dose is divided into smaller doses called
fractions. One fraction is usually given each day, five
days a week for six to seven weeks. However, each
radiation plan is individualized depending on the
type and location of the cancer and what other treatments are also being used. The actual administration
of the therapy usually takes about half an hour daily,
although radiation is administered for only from one
to five minutes at each session. It is important to
attend every scheduled treatment to get the most benefit from radiation therapy.
Recently, trials have begun to determine if there are
ways to deliver radiation fractions so that they kill more
cancer cells or have fewer side effects. Some trials use
smaller doses given more often. Up-to-date information
3138

on voluntary participation in clinical trials and where
they are being held is available by entering the search
term ‘‘radiation therapy’’ at the following web sites:


National Cancer Institute. <http://cancertrials.nci
.nih.gov> or (800) 4-CANCER.



National Institutes of Health Clinical Trials.
<http://clinicaltrials.gov>



Center Watch: A Clinical Trials Listing. <http://
www.centerwatch.com>.

The type of machines used to administer external
radiation therapy and the material that provides the
radiation vary depending on the type and location of
the cancer. Generally, the patient puts on a hospital
gown and lies down or sits in a special chair. Parts of
the body not receiving radiation are covered with
special shields that block the rays. A technician then
directs a beam of radiation to a pre-determined spot
on the body where the cancer is located. The patient
must stay still during the administration of the radiation so that no other parts of the body are affected. As
an extra precaution in some treatments, special molds
are made to make sure the body is in the same position
for each treatment. However, the treatment itself is
painless, like having a bone x-rayed.
Internal radiation therapy
Internal radiation therapy is called brachytherapy, implant therapy, interstitial radiation, or intracavitary radiation. With internal radiation therapy, a bit
of radioactive material is sealed in an implant (sometimes called a seed or capsule). The implant is then
placed very close to the cancer. The advantage of
internal radiation therapy is that it concentrates the
radiation near the cancer and lessens the chance of
damage to normal cells. Many different types of radioactive materials can be used in the implant, including
cesium, iridium, iodine, phosphorus, and palladium.
How the implant is put near the cancer depends on
the size and location of the cancer. Internal radiation
therapy is used for some cancers of the head, neck,
thyroid, breast, female reproductive system, and prostate. Most people will have the radioactive capsule
implanted by a surgeon while under either general or
local anesthesia at a hospital or surgical clinic.
Patients receiving internal radiation therapy do
become temporarily radioactive. They must remain
in the hospital during the time that the implant stays
in place. The length of time is determined by the type
of cancer and the dose of radioactivity to be delivered.
During the time the implant is in place, the patient will
have to stay in bed and remain reasonably still.
GALE ENCYCLOPEDIA OF MEDICINE

The implant usually can be removed in a simple
procedure without an anesthetic. As soon as the
implant is out of the body, the patient is no longer
radioactive, and restrictions on being with other people are lifted. Generally people can return to a level of
activity that feels comfortable to them as soon as the
implant is removed. Occasionally the site of the
implant is sore for some time afterwards. This discomfort may limit specific activities.
In some cases, an implant is left permanently
inside the body. People who have permanent implants
need to stay in the hospital and away from other
people for the first few days. Gradually the radioactivity of the implant decreases, and it is safe to be
around other people.
Radioimmunotherapy
Radioimmunotherapy is a promising way to treat
cancer that has spread (metastasized) to multiple locations throughout the body. Antibodies are immune
system proteins that specifically recognize and bind
to only one type of cell. They can be designed to bind
only with a certain type of cancer cell. To carry out
radioimmunotherapy, antibodies with the ability to
bind specifically to a patient’s cancer cells are attached
to radioactive material and injected into the patient’s
bloodstream. When these man-made antibodies find a
cancer cell, they bind to it. Then the radiation kills the
cancer cell. This process is still experimental, but
because it can be used to selectively attack only cancer
cells, it holds promise for eliminating cancers that have
spread beyond the primary tumor.
Radiation used to treat cancer
PHOTON RADIATION. Early radiation therapy
used x rays like those used to take pictures of bones,or
gamma rays. X rays and gamma rays are high energy
rays composed of massless particles of energy (like
light) called photons. The distinction between the
two is that gamma rays originate from the decay of
radioacive substances (like radium and cobalt-60),
while x rays are generated by devices that excite
electrons (such as cathode ray tubes and linear accelerators). These high energy rays act on cells by disrupting the electrons of atoms within the molecules
inside cells, disrupting cell functions, and most importantly stop their ability to divide and make new cells.

GALE ENCYCLOPEDIA OF MEDICINE

PARTICLE RADIATION. Particle radiation is radiation delivered by particles that have mass. Proton
therapy has been used since the early 1990s. Proton
rays consist of protons, a type of positively charged
atomic particle, rather than photons, which have
neither mass nor charge. Like x rays and gamma
rays, proton rays disrupt cellular activity. The advantage of using proton rays is that they can be shaped to
conform to the irregular shape of the tumor more
precisely than x rays and gamma rays. They allow
delivery of higher radiation doses to tumors without
increasing damage to the surrounding tissue.

Neutron therapy is another type of particle radiation. Neutron rays are very high-energy rays. They are
composed of neutrons, which are particles with mass
but no charge. The type of damage they cause to cells
is much less likely to be repaired than that caused by x
rays, gamma rays, or proton rays.
Neutron therapy can treat larger tumors than
conventional radiation therapy. Conventional radiation therapy depends on the presence of oxygen to
work. The center of large tumors lack sufficient oxygen to be susceptible to damage from conventional
radiation. Neutron radiation works in the absence of
oxygen, making it especially effective for the treatment
of inoperable salivary gland tumors, bone cancers,
and some kinds of advanced cancers of the pancreas,
bladder, lung, prostate, and uterus.
Recent advances in radiation therapy
A newer mode of treating brain cancers with radiation therapy is known as stereotactic radiosurgery. As
of the early 2000s, this approach is limited to treating
cancers of the head and neck because only these parts of
the body can be held completely still throughout the
procedure. Stereotactic radiosurgery allows the doctor
to deliver a single high-level dose of precisely directed
radiation to the tumor without damaging nearby
healthy brain tissue. The treatment is planned with the
help of three-dimensional computer-aided analysis of
CT and MRI scans. The patient’s head and neck are
held steady in a skeletal fixation device during the
actual treatment. Stereotactic radiosurgery can be
used in addition to standard surgery to treat a recurrent
brain tumor, or in place of surgery if the tumor cannot
be reached by standard surgical techniques.
Two major forms of stereotactic radiosurgery are
in use as of 2003. The gamma knife is a stationary
machine that is most useful for small tumors, blood
vessels, or similar targets. Because it does not move, it
can deliver a small, highly localized and precise beam of
radiation. Gamma knife treatment is done all at once in
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Radiation therapy

While the implant is in place, the patient’s contact
with other people will be limited. Healthcare workers
will make their visits as brief as possible to avoid
exposure to radiation, and visitors, especially children
and pregnant women, will be limited.

Radiation therapy

a single hospital stay. The second type of radiosurgery
uses a movable linear accelerator-based machine that is
preferred for larger tumors. This treatment is delivered
in several small doses given over several weeks.
Radiosurgery that is performed with divided doses is
known as fractionated radiosurgery. The total dose of
radiation is higher with a linear accelerator-based
machine than with gamma knife treatment.
Another advance in intraoperative radiotherapy
(IORT) is the introduction of mobile devices that
allow the surgeon to use radiotherapy in early-stage
disease and to operate in locations where it would be
difficult to transport the patient during surgery for
radiation treatment. Mobile IORT units have been
used successfully as of 2003 in treating early-stage
breast cancer and rectal cancer.
Radiation sensitizers are another recent innovation
in radiation therapy. Sensitizers are medications that
are given to make cancer cells easier to kill by radiation
than normal calls. Gemcitabine (Gemzar) is one of the
drugs most commonly used for this purpose.

Preparation
Before radiation therapy, the size and location of
the patient’s tumor are determined very precisely using
magnetic resonance imaging (MRI) and/or computed
tomography scans (CT scans). The correct radiation
dose, the number of sessions, the interval between
sessions, and the method of application are calculated
by a radiation oncologist based on the tumor type, its
size, and the sensitivity of the nearby tissues.
The patient’s skin is be marked with a semipermanent ink to help the radiation technologist achieve
correct positioning for each treatment. Molds may be
built to hold tissues in exactly the right place each time.

Aftercare
Many patients experience skin burn, fatigue,
nausea, and vomiting after radiation therapy regardless
of the where radiation is applied. After treatment, the
skin around the site of the treatment may also become
sore. Affected skin should be kept clean and can be
treated like sunburn, with skin lotion or vitamin A and
D ointment. Patients should avoid perfume and scented
skin products and protect affected areas from the sun.
Nausea and vomiting are most likely to occur when
the radiation dose is high or if the abdomen or another
part of the digestive tract is irradiated. Sometimes nausea
and vomiting occur after radiation to other regions, but
in these cases the symptoms usually disappear within a
3140

KEY TERMS
Anemia—Insufficient red blood cells in the body.
Antibody—Protein molecule that recognizes and
binds specifically to a foreign substance in the
body in order to eliminate it.
Chemotherapy—Injecting drugs into the body
where they circulate and kill cancer cells.
Computed tomography (CT or CAT) scan—Using x
rays taken from many angles and computer modeling, CT scans help locate and size tumors and
provide information on whether they can be surgically removed.
Fractionation—A procedure for dividing a dose of
radiation into smaller treatment doses.
Gamma rays—Short wavelength, high energy electromagnetic radiation emitted by radioactive
substances.
Hodgkin’s disease—Cancer of the lymphatic system, characterized by lymph node enlargement
and the presence of a large polyploid cells called
Reed-Sternberg cells.
Magnetic resonance imaging (MRI)—MRI uses
magnets and radio waves to create detailed crosssectional pictures of the interior of the body.
Stereotactic—Characterized by precise positioning in space. When applied to radiosurgery, stereotactic refers to a system of three-dimensional
coordinates for locating the target site.

few hours after treatment. Nausea and vomiting can be
treated with antacids, Compazine, Tigan, or Zofran.
Fatigue frequently starts after the second week of
therapy and may continue until about two weeks after
the therapy is finished. Patients may need to limit their
activities, take naps, and get extra sleep at night.
Patients should see their oncologist (cancer doctor) at least once within the first few weeks after their
final radiation treatment. They should also see an
oncologist every six to twelve months for the rest of
their lives so they can be checked to see if the tumor
has reappeared or spread.

Risks
Radiation therapy can cause anemia, nausea,
vomiting, diarrhea, hair loss, skin burn, sterility, and
rarely death. However, the benefits of radiation
therapy almost always exceed the risks. Patients
GALE ENCYCLOPEDIA OF MEDICINE

Radical neck dissection
Definition

Normal results
The outcome of radiation treatment varies
depending on the type, location, and stage of the
cancer. For some cancers such as Hodgkin’s disease,
about 75% of the patients are cured. Prostate cancer
also responds well to radiation therapy. Radiation to
painful bony metastases is usually a dramatically
effective form of pain control. Other cancers may be
less sensitive to the benefits of radiation.
Resources
PERIODICALS

Goer, D. A., C. W. Musslewhite, and D. M. Jablons.
‘‘Potential of Mobile Intraoperative Radiotherapy
Technology.’’ Surgical Oncology Clinics of North
America 12 (October 2003): 943–954.
Lawrence, T. S. ‘‘Radiation Sensitizers and Targeted
Therapies.’’ Oncology (Huntington) 17 (December
2003): 23–28.
Merrick, H. W. IIIrd, L. L. Gunderson, and F. A. Calvo.
‘‘Future Directions in Intraoperative Radiation
Therapy.’’ Surgical Oncology Clinics of North America
12 (October 2003): 1099–1105.
Nag, S., and K. S. Hu. ‘‘Intraoperative High-Dose-Rate
Brachytherapy.’’ Surgical Oncology Clinics of North
America 12 (October 2003): 1079–1097.
Witt, M. E., M. Haas, M. A. Marrinan, and C. N. Brown.
‘‘Understanding Stereotactic Radiosurgery for
Intracranial Tumors, Seed Implants for Prostate Cancer,
and Intravascular Brachytherapy for Cardiac Restenosis’’
Cancer Nursing 26 (December 2003): 494–502.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta GA
30329-4251. (800) ACS-2345. <http://
www.cancer.org>.
International Radiosurgery Support Association (IRSA).
3005 Hoffman Street, Harrisburg, PA 17110. (717)
260-9808. <http://www.irsa.org>.
National Association for Proton Therapy. 7910 Woodmont
Ave., Suite 1303, Bethesda, MD 20814. (301) 913-9360.
<http://www.proton-therapy.org/Default.htm>.
OTHER

Radiation Therapy and You. A Guide to Self-Help During
Treatment. National Cancer Institute CancerNet
Information Service. <http://cancernet.nci.nih.gov>.

Lorraine Lica, PhD
Rebecca J. Frey, PhD

Radiation treatments see Radiation therapy
GALE ENCYCLOPEDIA OF MEDICINE

Radical neck dissection is an operation used to
remove cancerous tissue in the head and neck.

Purpose
The purpose of radical neck dissection is to
remove lymph nodes and other structures in the head
and neck that are likely or proven to be malignant.
Variations on neck dissections exist depending on
the extent of the cancer. A radical neck dissection
removes the most tissue. It is done when the cancer
has spread widely in the neck. A modified neck dissection removes less tissue, and a selective neck dissection even less.

Precautions
This operation should not be done if cancer has
metastasized (spread) beyond the head and neck, or if
the cancer has invaded the bones of the cervical vertebrae (the first seven vertebrae of the spinal column)
or the skull. In these cases, the surgery will not effectively contain the cancer.

Description
Cancers of the head and neck (sometimes inaccurately called throat cancer) often spread to nearby
tissues and into the lymph nodes. Removing these
structures is one way of controlling the cancer.
Of the 600 hundred lymph nodes in the body,
about 200 are in the neck. Only a small number
of these are removed during a neck dissection. In
addition, other structures such as muscles, veins,
and nerves may be removed during a radical neck
dissection. These include the sternocleidomastoid
muscle (one of the muscles that functions to flex the
head), internal jugular (neck) vein, submandibular
gland (one of the salivary glands), and the spinal
accessory nerve (a nerve that helps control speech,
swallowing and certain movements of the head and
neck). The goal is always to remove all the cancer but
to save as many components surrounding the nodes
as possible.
Radical neck dissections are done in a hospital
under general anesthesia by a head and neck surgeon.
An incision is made in the neck, and the skin is pulled
back to reveal the muscles and lymph nodes. The
surgeon is guided in what to remove by tests done
3141

Radical neck dissection

should discuss the risks with their doctor and get a
second opinion about their treatment plan.

Radical neck dissection

prior to surgery and by examination of the size and
texture of the lymph nodes.

Preparation
Radical neck dissection is a major operation.
Extensive tests are done before the operation to try
to determine where and how far the cancer has
spread. These may include lymph node biopsies, CT
(computed tomography) scans, MRI scans, and barium swallows. In addition, standard pre-operative
blood and liver function tests are performed, and the
patient will meet with an anesthesiologist before the
operation. The patient should tell the anesthesiologist about all drug allergies and all medication
(prescription, non-prescription, or herbal) that he or
she is taking.

Aftercare

A digitized illustration of the human head and chest showing
nasal passages, sinuses, trachea, vascular nerves, as well as
ribs and parts of the lungs. (Custom Medical Stock Photo.
Reproduced by permission.)

A person who has had a radical neck dissection
will stay in the hospital several days after the operation, and sometimes longer if surgery to remove the
primary tumor was done at the same time. Drains
are inserted under the skin to remove the fluid that
accumulates in the neck area. Once the drains are
removed and the incision appears to be healing well,
patients are usually discharged from the hospital, but
will require follow-up doctor visits. Depending on
how many structures are removed, a person who has
had a radical neck dissection may require physical
therapy to regain use of the arm and shoulder.

Risks
The greatest risk in a radical neck dissection is
damage to the nerves, muscles, and veins in the
neck. Nerve damage can result in numbness (either
temporary or permanent) to different regions on the
neck and loss of function (temporary or permanent)
to parts of the neck, throat, and shoulder. The
more extensive the neck dissection, the more function
the patient is likely to lose. As a result, it is common
following radical neck dissection for a person to
have stooped shoulders, limited ability to lift the
arm, and limited head and neck rotation and flexion
due to the removal of nerves and muscles. Other
risks are the same as for all major surgery: potential
bleeding, infection, and allergic reaction to anesthesia.

Normal results
A specimen taken from radical neck surgery. (Custom Medical
Stock Photo. Reproduced by permission.)

3142

Normal lymph nodes are small and show no cancerous cells under the microscope.
GALE ENCYCLOPEDIA OF MEDICINE

Barium swallow—Barium is used to coat the throat
in order to take x-ray pictures of the tissues lining
the throat.
Computed tomography (CT or CAT) scan—Using x
rays taken from many angles and computer modeling, CT scans help size and locate tumors and
provide information on whether they can be surgically removed.
Lymphatic system—Primary defense against infection in the body. The tissues, organs, and channels
(similar to veins) that produce, store, and transport
lymph and white blood cells to fight infection.
Lymph nodes—Small, bean-shaped collections of
tissue found in lymph vessels. They produce cells
and proteins that fight infection and filter lymph.
Nodes are sometimes called lymph glands.
Malignant—Cancerous. Cells tend to reproduce
without normal controls on growth and form
tumors or invade other tissues.
Metastasize—Spread of cells from the original site
of the cancer to other parts of the body where
secondary tumors are formed.
Magnetic resonance imaging (MRI)—MRI uses
magnets and radio waves to create detailed crosssectional pictures of the interior of the body.

Abnormal results
Abnormal lymph nodes may be enlarged and show
malignant cells when examined under the microscope.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800) ACS-2345). <http://
www.cancer.org>.
Cancer Information Service. National Cancer Institute,
Building 31, Room 10A19, 9000 Rockville Pike,
Bethesda, MD 20892. (800) 4-CANCER. <http://
www.nci.nih.gov/cancerinfo/index.html>.
OTHER

The Voice Center at Eastern Virginia Medical School.
February 17, 2001. [cited June 7, 2001]. <http://
www.voice-center.com>.

John T. Lohr, PhD
Tish Davidson, A.M.
GALE ENCYCLOPEDIA OF MEDICINE

Radioactive implants
Definition
Radioactive implants are devices that are placed
directly within cancerous tissue or tumors, in order to
deliver radiation therapy intended to kill cancerous
cells. The practice of internal radiation therapy also
is referred to as brachytherapy.

Purpose
With the use of radioactive implants, the tumor is
subjected to radioactive activity over a longer period
of time, as compared to external beam therapy.

Precautions
The patient is required to remain in his or her bed
or room during the treatment. During the period of
greatest radioactivity (24–72 hours), health care providers will limit the amount of time spent with the
patient to that required for essential care. Some radiation exposure to family members has been noted with
certain radiation implants. However, a study in 2003
found that exposure to family members of prostate
cancer patients, an increasingly more commonly treated group of patients to receive implants, is low.

Description
Interstitial radiation therapy places the sources of
radiation directly into the tumor and surrounding
tissue. Most commonly used in tumors of the head,
neck, prostate, and breast, it also may be used in
combination with external radiation therapy. The
implant may be permanent or removable. A permanent implant of radioactive seeds, such as gold or
iodine, is placed directly into the organ. Over several
weeks or months, the seeds slowly deliver radiation to
the tumor. More commonly used is the removable
implant that requires an operation under general
anesthesia to place narrow, hollow stainless steel needles through the tumor. Teflon tubes are inserted
through the needles, and the needles are then removed.
After the patient returns to his or her room, radioactive seeds are inserted into the tubes in a procedure
called afterloading. Once the desired dosage is
reached, the tubes and seeds are removed.
The planning and procedures used for treatment
with radioactive implants is becoming increasingly
accurate and sophisticated as technology develops.
Special imaging tools and computer software help
physicians and radiation therapists visualize implant
3143

Radioactive implants

KEY TERMS

Rape and sexual assault

KEY TERMS
Ageusia—The loss of taste perception.
Alopecia—The loss of hair, or baldness.
Dysgeusia—Unpleasant alteration of taste sensation, often with a metallic taste.
Hypogeusia—Diminshed taste perception.

placements. Further, improved radiologic imaging
techniques help physicians track the progress of this
and other cancer therapies.
Intracavity radiation often is used for gynecologic
cancers. Under general or spinal anesthesia, hollow
applicators are placed directly inside the affected
organ. Correct positioning is confirmed by x rays,
and once the patient has returned to his or her room,
a small plastic tube containing the radioactive isotope
is inserted into the hollow applicator. The treatment is
delivered over 48–72 hours, after which time the applicator and radioactive sources are removed. Very high
doses of radiation can be delivered to the tumor, while
the rapid removal of the radioactive dose limits
damage to the surrounding structures.

Abnormal results
Normal cells are subjected to the effects of radiation; any tissue near the radiation site may be damaged
or destroyed. Some side effects are acute and temporary, while others develop over time and may be
permanent. Skin reactions, such as redness, itching,
flaking, or stripping of the top layer, usually are temporary; long-term effects can include scarring, and
changes in texture. Radiation recall is a delayed skin
side effect in which the area that had been exposed to
radiation becomes irritated or blistered after the
patient receives certain chemotherapy.
Following treatment for tumors of the head and
neck region, the lining of the mouth and throat can
become inflamed or irritated, resulting in a condition
known as mucositis or stomatitis. Injury to the salivary
glands can decrease saliva production, resulting in a
condition known as xerostomia, or dry mouth. There
also may be alteration in the patient’s taste buds,
resulting in decrease or loss of taste sensation (hypogeusia or ageusia), or the presence of unpleasant taste,
sometimes described as metallic (dysgeusia). Patients
may experience nausea and vomiting as a result of the
effect of radiation on the brain. Hair loss (alopecia)
may result from radiation’s effect on hair follicles.
3144

Radiation’s effect on the rapidly growing cells of
the gastrointestinal tract may result in diarrhea or
abdominal cramping. Pelvic radiation can affect the
bowel, bladder, or sexual function. Radiation also can
affect production of blood cell components in the bone
marrow.
Resources
PERIODICALS

‘‘Brachytherapy Software Receives FDA
Approval.’’Urology Times August 2003: 48.
‘‘Radiation Exposure Among Family Members of Prostate
Brachytherapy Patients Appears to be Low.’’Urology
Times September 2003: 12.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345.
<http://www.cancer.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Kathleen D. Wright, RN
Teresa G. Odle

Radioactive iodine uptake test see Thyroid
nuclear medicine scan
Radioallergosorbent test (RAST) see Allergy
tests
Radiotherapy see Radiation therapy
Raloxifene see Bone disorder drugs
Range-of-motion exercises see Exercise

Rape and sexual assault
Definition
The various definitions of rape range from the
broad (coercing a person to engage in any sexual act)
to the specific (forcing a woman to submit to sexual
intercourse). The United States Code includes the
crime of rape under the more comprehensive term
‘‘sexual abuse.’’ Two types of sexual assault are
defined in the code: sexual abuse and aggravated sexual abuse. Sexual abuse includes acts in which an
individual is forced to engage in sexual activity by
use of threats or other fear tactics, or instances in
which an individual is physically unable to decline.
Aggravated sexual abuse occurs when an individual
is forced to submit to sexual acts by use of physical
GALE ENCYCLOPEDIA OF MEDICINE

What To Do If You Are Raped

Don’t bathe
Don’t blame yourself
Retain all evidence
Get examined
Consider the ‘‘morning-after’’ pill

Description
Many misconceptions exist about rape and sexual
assault. It is often assumed that rape victims are all
women who have been attacked by a total stranger
and forced into having sexual intercourse. In reality,
sexual assault can take many forms—it may be violent
or nonviolent; the victim may be male or female, child
or adult; the offender may be a stranger, relative,
friend, authority figure, or spouse.
The number of sexual assaults reported depends
on how those abuses are defined. The United States
Code uses two terms to distinguish between different
sexual activities:


Sexual act: contact between penis and vagina or
penis and anus that involves penetration; contact
between the mouth and genitals or anus; penetration
of the vagina or anus with an object; or direct touching (not through clothing) of the genitals of an
individual under the age of 16.



Sexual contact: intentional touching of the genitals,
breasts, buttocks, anus, inner thigh, or groin with no
sexual penetration.

fears retaliation from the offender. He or she may be
afraid of family, friends, the community, or the media
learning about the offense. There may be a concern
about being judged or blamed by others. The victim
may think that no one will believe the assault
occurred.
THE VICTIMS. The 2000 ‘‘Victim, Incident, and
Offender Characteristics,’’ published by the National
Center for Juvenile Justice (NCJJ), analyzed sexual
assault data collected by law enforcement agencies
over a five-year span. The following characteristics
were found to be significant among victims of sexual
assault:


Age: Over two-thirds of reported victims of sexual
assault were juveniles under the age of 18. Twelve to
18 year olds represented the largest group of victims at
33%; 20% were between the ages of six and 11;
children less than five years old and adults between
18 and 24 years of age each constituted 14% of victims; 12% were between the ages of 25 and 34; and 7%
were over the age of 34. Persons over the age of 54
represented 1% of all victims. One out of every seven
victims surveyed in the study were under the age of six.



Gender: Females were more than six times more likely
to be a victim of sexual assault then males; more than
86% of victims were females. The great majority (99%)
of the victims of forcible rapes were women, while men
constituted the majority (54%) of the victims of forcible sodomy (oral or anal intercourse). Females are
most likely to be the victim of sexual assault at age 14,
while males are at most risk at age four.



Location: The residence of the victim was the most
commonly noted location of sexual assault (70%).
Other common locations included schools, hotels/
motels, fields, woods, parking lots, roadways, and
commercial/office buildings.



Weapons: A personal weapon (hands, feet, or fists)
was used in 77% of cases. No weapon was noted in
14% of assaults; other weapons (knifes, clubs, etc.)
were used in 6% of cases. Firearms were involved in
only 2% of assaults.

National statistics
According to the Federal Bureau of
Investigation’s Uniform Crime Reports, there were
95,136 forcible rapes reported to United States law
enforcement agencies in 2002. Sixty-five out of every
100,000 women were reported to be victims of rape
that year, up 4.7% from 2001 but down 3.9% from
1998. The actual number of rapes and sexual assaults,
however, is in reality much larger; estimates of unreported rape range between 2 and 10 times the number
reported to law enforcement. The National Violence
Against Women Survey, jointly sponsored by the
Centers for Disease Control and Prevention (CDC)
and the National Institute of Justice (NIJ) and conducted in the mid-1900s, found that one in six women
(18%) and one in 33 men (3%) has experienced an
attempted or completed rape. The survey estimated
that approximately 17,722,672 women and 2,782,440
men in the United States have been raped or have had
rape attempted as a child or adult, and that 302,091
women and 92,748 men were raped in the 12 months
prior to the study.
There are numerous reasons why the majority of
sexual assaults are never reported. Often the victim
GALE ENCYCLOPEDIA OF MEDICINE

Rape and sexual assault

force; threats of death, injury, or kidnapping; or substances that render that individual unconscious or
impaired.

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Rape and sexual assault

THE OFFENDERS. Similar statistics were gathered
by the NCJJ regarding the perpetrators of rape and
sexual assault. These characteristics included:








Common Misconceptions Of Males Perpetrating Date Rape

Age: Over 23% of offenders were under the age of 18;
juveniles were more likely to be perpetrators of forcible sodomy and fondling. The remaining 77% of
offenders were adults and were responsible for 67%
of juvenile victims. For younger juvenile victims
(under the age of 12), juvenile offenders were responsible for approximately 40% of assaults.
Gender: The great majority of all reported offenders
were male (96%). The number of female offenders
rose for victims under the age of six (12%), in contrast
to 6% for victims aged six through 12, 3% for victims
aged 12 through 17, and 1% for adult victims.
Relationship with offender: Approximately 59% of
offenders were acquaintances of their victims, compared to family members (27%) or strangers (14%).
Family members were more likely to be perpetrators
against juveniles (34%) than against adults (12%). In
contrast, strangers accounted for 27% of adult victims and 7% of juveniles.
Past offenses: In 19% of juvenile cases, the victim
was not the only individual to be assaulted by the
offender, compared to only 4% of adult cases.

Since I took her out and paid for the date, she should have sex with me.
When she says no, she really means yes.
If she’s aroused, she wants to have sex.
She wouldn’t go parking with me if she didn’t want to have sex.
If she didn’t wan to have sex, why did she let me go as far as she did?
If she gets me erect, then it’s her responsibility to do something about it.
She’s slept with other people, so she should sleep with me.
We’ve had sex before, and she didn’t say no then.

to 32,100 pregnancies a year among women 18 years of
age or older. Approximately 50% of pregnant rape
victims had an abortion, 6% put the child up for
adoption, and 33% kept the child (the remaining pregnancies resulted in miscarriage).
MENTAL HEALTH PROBLEMS. Also known as rape
trauma syndrome, post-traumatic stress disorder
(PTSD) is a mental health disorder that describes a
range of symptoms often experienced by someone
who has undergone a severely traumatic event.
Approximately 31% of rape victims develop PTSD
as a result of their assault; victims are more than six
times more likely to develop PTSD than women who
have not been victimized.

Consequences
Victims of sexual assault may sustain a range of
injuries; male victims are more likely than females to
suffer severe physical trauma. The National Women’s
Study, funded by the National Institute of Drug Abuse,
found that more than 70% of rape victims report no
physical injuries as a result of their assault; only 4%
sustain serious injuries that require hospitalization. At
least 49% of victims, however, state that they feared
severe injuries or death during their assault. Fatalities
occur in approximately 0.1% of rape cases.
Sexually transmitted diseases (STDs) are a source
of concern for many victims of sexual assault. The
most commonly transmitted diseases are gonorrhea
(caused by Neisseria gonorrhoeae), chlamydia (caused
by Chlamydia trachomatis), trichomoniasis) (caused by
Trichomonas vaginalis), and genital warts (caused
by human papillomavirus). Syphilis (caused by
Treponema pallidum) and human immunodeficiency
virus (HIV) are also noted among some sexual assault
victims. The transmission rate of STDs is estimated to
be between 3.6% and 30% of rapes.
According to the National Women’s Study,
approximately 5% of adult female rape victims
become pregnant as a result of their assault, leading
3146

The symptoms of PTSD include:


recurrent memories or flashbacks of the incident



nightmares



insomnia



mood swings



difficulty concentrating



panic attacks



emotional numbness



depression



anxiety

Persons who have been sexually assaulted have
also been noted to have increased risk for developing
other mental health problems. Over those who have
not been victimized, rape victims are:


three times more likely to have a major depressive
episode



four times more likely to have contemplated suicide



thirteen times more likely to develop alcohol dependency problems



twenty-six times more likely to develop drug abuse
problems
GALE ENCYCLOPEDIA OF MEDICINE

Once a victim of sexual assault reports the crime
to local authorities, calls a rape crisis hotline, or
arrives at the emergency room to be treated for injuries, a multidisciplinary team is often formed to
address his or her physical, psychological, and judicial
needs. This team usually includes law enforcement
officers, physicians, nurses, mental health professionals, victim advocates, and/or prosecutors.
The victim of sexual assault may continue to feel
fear and anxiety for some time after the incident, and
in some instances this may significantly impact his or
her personal or professional life. Follow-up counseling should therefore be provided for the victim, particularly if symptoms of PTSD become evident.

Forensic medical examination
Because rape is a crime, there are certain requirements for medical evaluation of the patient and for
record keeping. The forensic medical examination is
an invaluable tool for collecting evidence against a
perpetrator that may be admissible in court. Since
the great majority of victims know their assailant, the
purpose of the medical examination is often not to
establish identity but to establish nonconsensual sexual contact. The Sexual Assault Nurse Examiner program is an effective model that is used in many United
States hospitals and clinics to collect and document
evidence, evaluate and treat for STDs and pregnancy,
and refer victims to follow-up medical care and counseling. The ‘‘Sexual Assault Nurse Examiner
Development and Operation Guide,’’ prepared by
the Sexual Assault Resource Service, describes the
ideal protocol for collecting evidence from a sexual
assault victim. This includes:


performing the medical examination within 72 hours
of the assault



taking a history of the assault



documenting the general health of the victim, including menstrual cycle, potential allergies, and pregnancy status



assessment for trauma and taking photographic evidence of injuries



taking fingernail clippings or scrapings



taking samples for sperm or seminal fluid



combing head/pubic hair for foreign hairs, fibers,
and other substances



collection of bloody, torn, or stained clothing



taking samples for blood typing and DNA screening

GALE ENCYCLOPEDIA OF MEDICINE

Prevention
STD Prevention
While the concern of sexual assault victims of
contracting an STD is often high, the actual risk of
transmission is relatively low; the CDC estimates that
the risk of contracting gonorrhea from an offender is
between 6% and 12%, chlamydia between 4% and
17%, syphilis between 0.5% and 3%, and HIV less
than 1%. Nonetheless, post-exposure prophylaxis
(preventative treatment) against certain STDs is
often provided for the victim. Treatment with zidovudine, for example, is recommended for individuals
who are at a high risk of exposure to HIV. The CDC
recommends the following prophylactic regimen be
provided for victims of sexual assaults in which vaginal, oral, or anal penetration took place:


a single dose of ceftriaxone, an antibiotic effective
against Neisseria gonorrhoeae



a single dose of metronidazole, an antibiotic effective
against Trichomonas vaginalis



a single dose of azithromycin or doxycycline, antibiotics effective against Chlamydia trachomatis



inoculation with the post-exposure hepatitis B
vaccine

In some instances, cultures may be taken during
the medical examination and at time points afterward
to test for gonorrhea or chlamydia. It is important that
the victim receive information regarding the symptoms of STDs and be counseled to return for further
examination if any of these symptoms occur.
Pregnancy prevention
Female victims at risk for becoming pregnant
after an assault should be counseled on the availability
of emergency contraception. According to the Food
and Drug Administration (FDA), emergency contraception is not effective if there is no pregnancy but
works to prevent pregnancy from occurring by delaying or preventing ovulation, by affecting the transport
of sperm, and/or by thinning the inner layer of the
uterus (endometrium) so that implantation is prevented. It is therefore not a form of abortion.
A number of options are available for women if
they choose to use emergency contraceptives to prevent pregnancy following a sexual assault. The Yupze
regimen uses two oral contraceptive pills that contain
both of the hormones estrogen and progestin. The risk
of pregnancy is reduced by 75% after use of the Yupze
regimen, reducing the average number of pregnancies
after unprotected sex from eight in 100 to two in 100.
3147

Rape and sexual assault

Treatment

Rape and sexual assault

PERIODICALS

KEY TERMS
Aggravated sexual abuse—When an individual is
forced to submit to sexual acts by use of physical
force; threats of death, injury, or kidnapping; or
substances that render that individual unconscious
or impaired.
Forcible sodomy—Forced oral or anal intercourse.
Forensic—Pertaining to or used during legal
proceedings.
Post-traumatic stress disorder (PTSD)—Also
known as rape trauma syndrome; a mental health
disorder that describes a range of symptoms often
experienced by someone who has undergone a
severely traumatic event.
Sexual abuse—When an individual is forced to
engage in sexual activity by use of threats or other
fear tactics, or instances in which an individual is
physically unable to refuse.
Sexual assault nurse examiner (SANE)—A registered nurse who is trained to collect and document
evidence from a sexual assault victim, evaluate and
treat for STDs and pregnancy, and refer victims to
follow-up medical care and counseling.
Yupze regimen—A form of emergency contraception in which two oral contraceptive pills that contain both of the hormones estrogen and progestin
are taken to prevent pregnancy.

Progestin-only oral contraceptives are also available
and reduce the risk of pregnancy by 89% to 95%.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders, 4th ed., revised. Washington,
DC: American Psychiatric Association, 2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Medical Examination of the Rape Victim.’’ Section 18,
Chapter 244 In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychosexual Disorders.’’ Section 15, Chapter 192 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Federal Bureau of Investigation. Uniform Crime Reports:
Crime in the United States—2002. Washington, DC:
Government Printing Office, 2003.
3148

Brewin, C. R., and E. A. Holmes. ‘‘Psychological Theories of
Posttraumatic Stress Disorder.’’ Clinical Psychology
Review 23 (May 2003): 339–376.
Bushman, B. J., A. M. Bonacci, M. van Dijk, and R. F.
Baumeister. ‘‘Narcissism, Sexual Refusal, and
Aggression: Testing a Narcissistic Reactance Model of
Sexual Coercion.’’ Journal of Personal and Social
Psychology 84 (May 2003): 1027–1040.
Frazier, P. A. ‘‘Perceived Control and Distress Following
Sexual Assault: A Longitudinal Test of a New Model.’’
Journal of Personal and Social Psychology 84 (June
2003): 1257–1269.
Koss, M. P., K. J. Bachar, and C. Q. Hopkins. ‘‘Restorative
Justice for Sexual Violence: Repairing Victims,
Building Community, and Holding Offenders
Accountable.’’ Annals of the New York Academy of
Science 989 (June 2003): 384–396.
Reynolds, Matthew W., Jeffery Peipert, and Beverly Collins.
‘‘Epidemiologic Issues of Sexually Transmitted
Diseases in Sexual Assault Victims.’’ Obstetrical and
Gynecological Survey 55 (January 2000): 51–57.
ORGANIZATIONS

American Psychiatric Association (APA). 1400 K Street,
NW, Washington, DC 20005. (888) 357-7924. <http://
www.psych.org>.
Federal Bureau of Investigation. J. Edgar Hoover Building,
935 Pennsylvania Avenue, NW, Washington, DC
20535-0001. (202) 324-3000. <http://www.fbi.gov>.
Rape, Abuse, and Incest National Network. 635-B
Pennsylvania Ave. SE, Washington, DC 20003. (800)
656-HOPE.
United States Department of Justice, Office for Victims of
Crime. 810 7th Street NW, Washington, DC 20531.
OTHER

Kilpatrick, Dean G., Anna Whalley, and Christine
Edmunds. ‘‘Sexual Assault.’’ In 2000 National Victim
Assistance Academy Textbook, edited by Anne
Seymour, Morna Murray, Jane Sigmon, Christine
Edmunds, Mario Gaboury, and Grace Coleman.
October 2000.
Ledray, Linda E. ‘‘Sexual Assault Nurse Examiner
Development and Operation Guide.’’ Sexual Assault
Resource Service. August 1999.
‘‘National Crime Victim’s Rights Week: Resource Guide.’’
U.S. Department of Justice, Office for Victims of Crime.
April 2001.
‘‘Rape Fact Sheet: Prevalence and Incidence.’’ Centers for
Disease Control and Prevention. February 10, 2000.
Snyder, Howard N. ‘‘Sexual Assault of Young Children as
Reported to Law Enforcement: Victim, Incident, and
Offender Characteristics.’’ National Center for Juvenile
Justice. July 2000.

Stéphanie Dionne
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

nutritional disorders. For example, scurvy, a disease
caused by a lack of Vitamin C, has a rash as one of its
symptoms.



cancer. A few types of cancer, such as chronic lymphocytic leukemia, can be the underlying cause of a
rash.

Rashes
Definition
The popular term for a group of spots or red,
inflamed skin that is usually a symptom of an underlying condition or disorder. Often temporary, a rash is
only rarely a sign of a serious problem.

Description
A rash may occur on only one area of the skin, or
it could cover almost all of the body. Also, a rash may
or may not be itchy. Depending on how it looks, a rash
may be described as:


blistering (raised oval or round collections of fluid
within or beneath the outer layer of skin)



macular (flat spots)



nodular (small, firm, knotty rounded mass)



papular (small solid slightly raised areas)



pustular (pus-containing skin blister).

Causes and symptoms
There are many theories as to the development of
skin rashes, but experts are not completely clear what
causes some of them. Generally a skin rash is an
intermittent symptom, fading and reappearing.
Rashes may accompany a range of disorders and conditions, such as:






Infectious illness. A rash is symptom of many different kinds of childhood infectious illnesses, including
chickenpox and scarlet fever. It may be triggered by
other infections, such as Rocky Mountain spotted
fever or ringworm.
Allergic reactions. One of the most common symptoms of an allergic reaction is an itchy rash. Contact
dermatitis is a rash that appears after the skin is
exposed to an allergen, such as metal, rubber, some
cosmetics or lotions, or some types of plants (e.g.
poison ivy). Drug reactions are another common
allergic cause of rash; in this case, a rash is only one
of a variety of possible symptoms, including fever,
seizures, nausea and vomiting, diarrhea, heartbeat
irregularities, and breathing problems. This rash
usually appears soon after the first dose of the course
of medicine is taken.
Autoimmune disorders. Conditions in which the
immune system turns on the body itself, such as
systemic lupus erythematosus or purpura, often have
a characteristic rash.

GALE ENCYCLOPEDIA OF MEDICINE

Rashes in infancy
Rashes are extremely common in infancy, and are
usually not serious at all and can be treated at home.
Diaper rash is caused by prolonged skin contact
with bacteria and the baby’s waste products in a damp
diaper. This rash has red, spotty sores and there may
be an ammonia smell. In most cases the rash will
respond within three days to drying efforts. A diaper
rash that does not improve in this time may be a yeast
infection requiring prescription medication. A doctor
should be consulted if the rash is solid, bright red,
causes fever, or the skin develops blisters, boils, or pus.
Infants also can get a rash on cheeks and chin
caused by contact with food and stomach contents.
This rash will come and go, but usually responds to a
good cleaning after meals. About a third of all infants
develop ‘‘acne’’ usually after the third week of life in
response to their mothers’ hormones before birth. This
rash will disappear between weeks and a few months.
Heat rash is a mass of tiny pink bumps on the back of
the neck and upper back caused by blocked sweat
glands. The rash usually appears during hot, humid
weather, although a baby with a fever can also develop
the rash.
A baby should see a doctor immediately if the
rash:


appears suddenly and looks purple or blood-colored



looks like a burn



appears while the infant seems to be sick

Diagnosis
A physician can make a diagnosis based on the
medical history and the appearance of the rash, where
it appears, and any other accompanying symptoms.

Treatment
Treatment of rashes focuses on resolving the underlying disorder and providing relief of the itching that
often accompanies them. Soothing lotions or oral antihistamines can provide some relief, and topical antibiotics may be administered if the patient, particularly a
child, has caused a secondary infection by scratching.
3149

Rashes



Rat-bite fever

Prognosis
Most rashes that have an acute cause, such as an
infection or an allergic reaction, will disappear as soon
as the infection or irritant is removed from the body’s
system. Rashes that are caused by chronic conditions,
such as autoimmune disorders, may remain indefinitely or fade and return periodically.

Prevention
Some rashes can be prevented, depending on the
triggering factor. A person known to be allergic to
certain drugs or substances should avoid those things
in order to prevent a rash. Diaper rash can be prevented
by using cloth diapers and keeping the diaper area very
clean, breast feeding, and changing diapers often.
Resources
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.

Carol A. Turkington

An unidentified rash on young boy’s back. (Custom Medical
Stock Photo. Reproduced by permission.)

KEY TERMS
Purpura—A group of disorders characterized by
purple or red brown areas of discoloration visible
through the skin.
Scurvy—A nutritional disorder that causes skin
bruising and hemorrhages.

The rash triggered by allergies should disappear as soon
as the allergen is removed; drug rashes will fade when
the patient stops taking the drug causing the allergy. For
the treatment of diaper rash, the infant’s skin should be
exposed to the air as much as possible; ointments are not
needed unless the skin is dry and cracked. Experts also
recommend switching to cloth diapers and cleaning
affected skin with plain water.
3150

Rat-bite fever
Definition
Rat-bite fever refers to an infection which develops after having been bitten or scratched by an
infected animal.

Description
Rat-bite fever occurs most often among laboratory workers who handle lab rats in their jobs, and
among people who live in poor conditions, with rodent
infestation. Children are particularly likely to be bitten
by rodents infesting their home, and are therefore
most likely to contract rat-bite fever. Other animals
that can carry the types of bacteria responsible for this
illness include mice, squirrels, weasels, dogs, and cats.
One of the causative bacteria can cause the same illness if it is ingested, for example in unpasteurized milk.

Causes and symptoms
There are two variations of rat-bite fever, caused
by two different organisms. In the United States, the
GALE ENCYCLOPEDIA OF MEDICINE

Streptobacillary rat-bite fever occurs up to 22
days after the initial bite or scratch. The patient
becomes ill with fever, chills, nausea and vomiting,
headache, and pain in the back and joints. A rash
made up of tiny pink bumps develops, covering the
palms of the hands and the soles of the feet. Without
treatment, the patient is at risk of developing serious
infections of the lining of the heart (endocarditis), the
sac containing the heart (pericarditis), the coverings of
the brain and spinal cord (meningitis), or lungs (pneumonia). Any tissue or organ throughout the body may
develop a pocket of infection and pus, called an
abscess.
Spirillary rat-bite fever occurs some time after the
initial injury has already healed, up to about 28 days
after the bite or scratch. Although the wound had
appeared completely healed, it suddenly grows red
and swollen again. The patient develops a fever.
Lymph nodes in the area become swollen and tender,
and the patient suffers from fever, chills, and headache. The skin in the area of the original wound
sloughs off. Although rash is less common than with
streptobacillary rat-bite fever, there may be a lightly
rosy, itchy rash all over the body. Joint and muscle
pain rarely occur. If left untreated, the fever usually
subsides, only to return again in repeated two- to fourday cycles. This can go on for up to a year, although,
even without treatment, the illness usually resolves
within four to eight weeks.

Diagnosis
In streptobacillary rat-bite fever, found in the
United States, diagnosis can be made by taking a
sample of blood or fluid from a painful joint. In a
laboratory, the sample can be cultured, to allow the
growth of organisms. Examination under a microscope will then allow identification of the bacteria
Streptobacillus moniliformis.
In spirillary rat-bite fever, diagnosis can be made
by examining blood or a sample of tissue from the
wound for evidence of Spirillum minus.

Treatment
Shots of procaine penicillin G or penicillin V by
mouth are effective against both streptobacillary and
spirillary rat-bite fever. When a patient is allergic to
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Abscess—A pocket of infection; a collection of pus.
Endocarditis—An inflammation of the lining of the
heart.
Meningitis—An inflammation of the tissues covering the brain and spinal cord.
Pasteurization—A process during which milk is
heated up and maintained at a particular temperature long enough to kill bacteria.
Pericarditis—An inflammation of the sac containing the heart.

the penicillins, erythromycin may be given by mouth
for streptobacillary infection, or tetracycline by mouth
for spirillary infection.

Prognosis
With treatment, prognosis is excellent for both
types of rat-bite fever. Without treatment, the spirillary form usually resolves on its own, although it may
take up to a year to do so.
The streptobacillary form, found in the United
States, however, can progress to cause extremely serious, potentially fatal complications. In fact, before
antibiotics were available to treat the infection, streptobacillary rat-bite fever frequently resulted in death.

Prevention
Prevention involves avoiding contact with those
animals capable of passing on the causative organisms. This can be an unfortunately difficult task for
people whose economic situations do not allow them
to move out of rat-infested buildings. Because streptobacillary rat-bite fever can occur after drinking contaminated milk or water, only pasteurized milk, and
water from safe sources, should be ingested.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Rational-emotive therapy see Cognitivebehavioral therapy
3151

Rat-bite fever

bacteria Streptobacillus moniliformis is the most common cause (causing streptobacillary rat-bite fever). In
other countries, especially Africa, Spirillum minus
causes a different form of the infection (called spirillary rat-bite fever).

Raynaud’s disease

Raynaud’s disease
Definition
Raynaud’s disease refers to a disorder in which the
fingers or toes (digits) suddenly experience decreased
blood circulation. It is characterized by repeated episodes of color changes of the skin of digits on cold
exposure or emotional stress.

Description
Raynaud’s disease can be classified as one of two
types: primary (or idiopathic) and secondary (also
called Raynaud’s phenomenon). Primary Raynaud’s
disease has no predisposing factor, is more mild, and
causes fewer complications. About half of all cases of
Raynaud’s disease are of this type. Women are five
times more likely than men to develop primary
Raynaud’s disease. The average age of diagnosis is
between 20 and 40 years. Approximately three out of
ten people with primary Raynaud’s disease eventually
progress to secondary Raynaud’s disease after diagnosis. About 15% of individuals improve.
Secondary Raynaud’s disease is the same as primary Raynaud’s disease, but occurs in individuals
with a predisposing factor, usually a form of collagen
vascular disease. What is typically identified as primary Raynaud’s is later identified as secondary once
a predisposing disease is diagnosed. This occurs in
approximately 30% of patients. As a result, the secondary type is often more complicated and severe, and
is more likely to worsen.
Several related conditions that predispose persons
to secondary Raynaud’s disease include scleroderma,
systemic lupus erythematosus, rheumatoid arthritis and
polymyositis. Pulmonary hypertension and some nervous system disorders such as herniated discs and
tumors within the spinal column, strokes, and polio
can progress to Raynaud’s disease. Finally, injuries
due to mechanical trauma caused by vibration (such
as that associated with chain saws and jackhammers),
repetitive motion (carpal tunnel syndrome), electrical
shock, and exposure to extreme cold can led to the
development of Raynaud’s disease. Some drugs used
to control high blood pressure or migraine headaches
have been known to cause Raynaud’s disease.
The prevalence of Reynaud’s Phenomena in the
general population varies 4–15%. Females are seven
times more likely to develop Raynaud’s diseases than
are men. The problem has not been correlated with
coffee consumption, dietary habits, occupational
3152

history (excepting exposure to vibration) and exposure to most drugs. An association between
Raynaud’s disease and migraine headaches and has
been reported. Secondary Raynaud’s disease is common among individuals systemic lupus erythematosus
in tropical countries.

Causes and symptoms
There is significant familial aggregation of primary Raynaud’s disease. However, no causative gene
has been identified.
Risk factors for Raynaud’s disease differ between
males and females. Age and smoking seem to be associated with Raynaud’s disease only in men, while the
associations of marital status and alcohol use with
Raynaud’s disease are usually only observed in
women. These findings suggest that different mechanisms influence the expression of Raynaud’s disease in
men and women.
Both primary and secondary Raynaud’s disease
signs and symptoms are thought to be due to arterioles
over-reacting to stimuli. Cold normally causes the tiny
muscles in the walls of arteries to contract, thus reducing the amount of blood that can flow through them.
In people with Raynaud’s disease, the extent of constriction is extreme, thus severely restricting blood
flow. Attacks or their effects may be brought on or
worsened by anxiety or emotional distress.
There are three distinct phases to an episode of
Raynaud’s disease. When first exposed to cold, small
arteries respond with intense contractions (vasoconstriction). The affected fingers or toes (in rare
instances, the tip of the nose or tongue) become pale
and white because they are deprived of blood and,
thus, oxygen. In response, capillaries and veins expand
(dilate). Because these vessels are carrying deoxygenated blood, the affected area then becomes blue in
color. The area often feels cold and tingly or numb.
After the area begins to warm up, the arteries dilate.
Blood flow is significantly increased. This changes the
color of the area to a bright red. During this phase,
persons often describe the affected area as feeling
warm and throbbing painfully.
Raynaud’s disease may initially affect only the
tips of fingers or toes. As the disease progresses, it
may eventually involve all of one or two digits.
Ultimately, all the fingers or toes may be affected.
About one person in ten, will experience a complication called sclerodactyly. In sclerodactyly, the skin
over the involved digits becomes tight, white, thick,
smooth and shiny. In approximately 1% of cases of
GALE ENCYCLOPEDIA OF MEDICINE

Treatment

A close-up view of a patient’s fingers afflicted with Raynaud’s
disease. While this disorder may initially only affect the tips
of the fingers and toes, eventually blood circulation of the
entire finger or toe is affected. (Custom Medical Stock Photo.
Reproduced by permission.)

Raynaud’s disease, deep sores (ulcers) may develop in
the skin. In rare cases of frequent, repetitive bouts of
severe ischemia (decreased supply of oxygenated blood
to tissues or organs), tissue loss, or gangrene may
result and amputation may be required.

Diagnosis
Primary Raynaud’s disease is diagnosed following
the Allen Brown criteria. There are four components.
The certainty of the diagnosis and severity of the disease increase as more criteria are met. The first is that
at least two of the three color changes must occur
during attacks provoked by cold and or stress. The
second is that episodes must periodically occur for at
least two years. The third is that attacks must occur in
both the hands and the feet in the absence of vascular
occlusive disease. The last is that there is no other
identifiable cause for the Raynaud’s episodes.
A cold stimulation test may also be performed to
help to confirm a diagnosis of Raynaud’s disease. The
temperature of affected fingers or toes is taken. The
hand or foot is then placed completely into a container
of ice water for 20 seconds. After removal from the
water, the temperature of the affected digits is immediately recorded. The temperature is retaken every five
minutes until it returns to the pre-immersion level.
Most individuals recover normal temperature within
15 minutes. People with Raynaud’s disease may
require 20 minutes or more to reach their pre-immersion temperature.
Laboratory testing is performed frequently.
However, these results are often inconclusive for several reasons. Provocative testing such as the ice
GALE ENCYCLOPEDIA OF MEDICINE

There is no known way to prevent the development of Raynaud’s disease. Further, there is no known
cure for this condition. Therefore, avoidance of the
trigger is the best supportive management available.
Most cases of primary Raynaud’s disease can be controlled with proper medical care and avoidance.
Many people are able to find relief by simply
adjusting their lifestyles. Affected individuals need to
stay warm, and keep their hands and feet well covered
in cold weather. Layered clothing, scarves, heavy
coats, heavy socks, and mittens under gloves are suggested because gloves alone allow heat to escape. It is
also recommended that patients cover or close the
space between their sleeves and mittens. Indoors,
they should wear socks and comfortable shoes.
Smokers should quit as nicotine will worsen the problem. Avoid the use of vibrating tools as well.
People with severe cases of Raynaud’s disease
may need to be treated with medications to help keep
the arterioles relaxed and dilated. Medications such as
calcium-channel blockers, reserpine or nitroglycerin
may be prescribed to relax artery walls and improve
blood flow.

Alternative Treatment
Because episodes of Raynaud’s disease have also
been associated with stress and emotional upset, the
condition may be improved by learning to manage
stress. Regular exercise is known to decrease stress
and lower anxiety. Hypnosis, relaxation techniques,
and visualization are also useful methods to help control emotions.
Biofeedback training is a technique during which a
patient is given continuous information on the temperature of his or her digits, and then taught to voluntarily control this temperature. Some alternative
practitioners believe that certain dietary supplements
and herbs may be helpful in decreasing the vessel
spasm of Raynaud’s disease. Suggested supplements
include vitamin E (found in fruits, vegetables, seeds,
3153

Raynaud’s disease

emergence just described, is difficult to interpret
because there is considerable overlap between normal
and abnormal results. The antinuclear antibody test of
blood is usually negative in Raynaud’s disease.
Capillary beds under finger nails usually appear normal. Erythrocyte sedimentation rates are often abnormal in people with connective tissue diseases.
Unfortunately, this finding is not consistent in people
with Raynaud’s disease.

Raynaud’s disease

Resources

KEY TERMS
Arteriole—The smallest type of artery.
Artery—A blood vessel that carries blood away
from the heart to peripheral tissues.
Gangrene—Death of a tissue, usually caused by
insufficient blood supply and followed by bacterial
infection of the tissue.
Idiopathic—Of unknown origin.
Polymyositis—An inflammation of many muscles.
Pulmonary hypertension—A severe form of high
blood pressure caused by diseased arteries in the
lung.
Rheumatoid arthritis—Chronic, autoimmune disease marked by inflammation of the membranes
surrounding joints.
Scleroderma—A relatively rare autoimmune disease affecting blood vessels and connective tissue
that makes skin appear thickened.
Systemic lupus erythematosus—A chronic inflammatory disease that affects many tissues and parts of
the body including the skin.

and nuts), magnesium (found in seeds, nuts, fish,
beans, and dark green vegetables), and fish oils. The
circulatory herbs cayenne, ginger and prickly ash may
help enhance circulation to affected areas.

Prognosis
The prognosis for most people with Raynaud’s
disease is very good. In general, primary Raynaud’s
disease has the best prognosis, with a relatively small
chance (1%) of serious complications. Approximately
half of all affected individuals do well by taking simple
precautions, and never require medication. The prognosis for people with secondary Raynaud’s disease (or
phenomenon) is less predictable. This prognosis
depends greatly on the severity of other associated
conditions such as scleroderma, lupus, or Sjögren
syndrome.

Prevention
There is no way to prevent the development of
Raynaud’s disease. Once an individual realizes that
he or she suffers from this disorder, however, steps
can be taken to reduce the frequency and severity of
episodes.
3154

BOOKS

Rosenwasser, Lanny J. ‘‘The Vasaculitic Syndromes.’’ In
Cecil Textbook of Medicine. Lee Goldman, et al.,
editors. Philadelphia: Saunders, 2000, pp. 1524-1527.
PERIODICALS

Fraenkel, L., et al. ‘‘Different Factors Influencing the
Expression of Raynaud’s Phenomenon in Men and
Women.’’ Arthritis and Rheumatology 42, no. 2
(February 1999): 306-310.
Voulgari, P. V., et al. ‘‘Prevalence of Raynaud’s
Phenomenon in a Healthy Greek Population.’’ Annals
of Rheumatic Disease 59, no. 3 (March 2000): 206-210.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave., Dallas,
TX 75231-4596. (214) 373-6300 or (800) 242-8721.
inquire@heart.org. <http://
www.americanheart.org>.
Irish Raynaud’s and Scleroderma Society. PO Box 2958
Foxrock, Dublin 18, Ireland (01) 235 0900.
irss@indigo.ie.
National Heart, Lung, and Blood Institute. PO Box 30105,
Bethesda, MD 20824-0105. (301) 592-8573. nhlbiinfo@rover.nhlbi.nih.gov. <http://
www.nhlbi.nih.gov>.
National Organization for Rare Disorders (NORD). PO
Box 8923, New Fairfield, CT 06812-8923. (203) 7466518 or (800) 999-6673. Fax: (203) 746-6481. <http://
www.rarediseases.org>.
Raynaud’s & Scleroderma Association (UK). 112 Crewe
Road, Alsager, Cheshire, ST7 2JA. UK (44) (0) 1270
872776. webmaster@raynauds.demon.co.uk. <http://
www.raynauds.demon.co.uk>.
OTHER

Arthritis Foundation. <http//www.arthritis-foundation
.com/>.
British Sjögren’s Syndrome Association. <http://ourworld
.copmpuserve.com/homepages/BSSAssociation>.
Raynaud’s & Scleroderma Association. <http://
www.Raunaud’s.demon.co,uk/>.
Rodriguez, J., and S. Wasson. ‘‘Raynaud’s Disease.’’ Wayne
State University School of Medicine. <http://
www.med.wayne.edu/raynauds/>.

L. Fleming Fallon, Jr., MD, PhD, DrPH

RDS see Respiratory distress syndrome
Reactive airway disease see Asthma
Reactive polycythemia see Secondary
polycythemia
Reading disorder see Learning disorders
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Recompression treatment is the use of elevated
pressure to treat conditions within the body after it
has been subjected to a rapid decrease in pressure. It
also includes hyperbaric oxygen therapy.

Purpose
Recompression treatment is used to overcome the
adverse effects of gas embolism and decompression
sickness (sometimes called the bends) in underwater
divers who breathe compressed air. It is also approved
for treatment of severe smoke inhalation, carbon monoxide poisoning, gas gangrene, radiation tissue
damage, thermal burns, extreme blood loss, crush injuries, and wounds that won’t heal.

Precautions
Hyperbaric oxygen therapy delivers greater
amounts of oxygen more quickly to the body than
breathing room air (which is only 21% oxygen) at
regular pressure. Unmonitored, increased oxygen can
produce toxic effects. Treatments must follow safe
time-dose limits and may only be administered by a
doctor.

Preparation
Oxygen is often administered to a patient as first
aid while he or she is being transported to a hyperbaric
chamber. The treatment begins with chamber compression; as the pressure of the chamber atmosphere
increases, the temperature also rises and the patient’s
ears may fill as they would during an airplane landing.
Swallowing and yawning are ways to relieve the inner
ear pressure. Once the desired pressure is achieved, the
patient is given pure oxygen to breathe. Because treatment is lengthy, patients are encouraged to sleep or
listen to music. In larger chambers, patients may also
read or watch videos.

Aftercare
Depending on the reason for treatment and the
treatment outcome, the patient may be taken to a
hospital for further care, or examined and released.

Description
Recompression treatment is performed in a hyperbaric chamber, a sealed compartment in which the
patient breathes normal air or ‘‘enhanced’’ air with
up to 100% oxygen while exposed to controlled pressures up to three times normal atmospheric pressure.
The patient may receive the oxygen through a face
mask, a hood or tent around the head, or an endotracheal tube down the windpipe if the patient is already
on a ventilator. When used to treat decompression
sickness or gas embolism, the increased pressure
reduces the size of gas bubbles in the patient’s body.
The increased oxygen concentration speeds the diffusion of the nitrogen within the bubbles out of the
patient’s body. As gas bubbles deflate, the trauma of
gas embolism and decompression sickness begins to
resolve. Treatment for diving emergencies typically
involves one session, lasting four to six hours, at
three atmospheres of pressure.
When used to treat other conditions, the increased
pressure allows oxygen and other gases to dissolve
more rapidly into the blood and thus be carried to
GALE ENCYCLOPEDIA OF MEDICINE

Risks
There is minimal risk when recompression treatment is administered by a competent physician.
However, some common side effects are sinus pain,
temporary changes in vision, and fatigue.

Normal results
With prompt and appropriate recompression
treatment, most patients show marked improvement
in their blood oxygen levels and tissue circulation, as
well as other signs of healing. Divers treated for gas
embolism or decompression sickness may recover with
no lasting effects.

Abnormal results
When recompression treatment is not begun
promptly or not conducted at adequate time-dose
levels, patients with decompression sickness may
develop bone necrosis. This significant destruction of
3155

Recompression treatment

Recompression treatment

oxygen-starved tissues to enhance healing. Elevated
oxygen levels can also purge toxins such as carbon
monoxide from the body. In addition, when body
tissues are super-saturated with oxygen, the destruction of some bacteria is enhanced and the spread of
certain toxins is halted. This makes hyperbaric oxygen
therapy useful in treating gas gangrene and infections
that cause tissue necrosis (death). Hyperbaric oxygen
therapy also promotes the growth of new blood
vessels.

Rectal cancer

KEY TERMS
Atmosphere—A measurement of pressure. One
atmosphere equals the pressure of air at sea level
(14.7 pounds per square inch [psi]).
Compressed air—Air that is held under pressure in
a tank to be breathed underwater by divers. A tank
of compressed air is part of a diver’s scuba (selfcontained underwater breathing apparatus) gear.
Decompression—A decrease in pressure from the
surrounding water that occurs with decreasing diving depth.
Decompression sickness—A condition found in
divers in which gas bubbles of nitrogen form in
tissues and blood vessels as a result of decreasing
surrounding pressure, such as in ascent from a dive.
It may be a painful condition, especially as nitrogen
bubbles invade the joints; persons stricken may
walk stooped over in pain, in a bent stance that
led to it being called ‘‘the bends.’’
Gas embolism—The presence of gas bubbles in the
bloodstream that obstruct circulation. Also called
air embolism.
Hyperbaric chamber—A sealed compartment in
which patients are exposed to controlled pressures
up to three times normal atmospheric pressure.
Hyperbaric treatment may be used to regulate
blood gases, reduce gas bubbles, and provide
higher levels of oxygen more quickly.
Recompression—Restoring the elevated pressure
of the diving environment to treat decompression
sickness and gas embolism by decreasing bubble
size.

bone, most commonly found in the hip and shoulder,
produces chronic pain and severe disability. Another
result of delayed or inadequate treatment may be permanent neurological damage. When decompression
sickness involves the spinal cord, partial paralysis
may occur.
Resources
ORGANIZATIONS

American College of Hyperbaric Medicine. P.O. Box 25914130, Houston, Texas 77265. (713) 528-0657. <http://
www.hyperbaricmedicine.org>.
Divers Alert Network. The Peter B. Bennett Center, 6 West
Colony Place, Durham, NC 27705. (800) 446-2671.
<http://www.diversalertnetwork.org>.
3156

Undersea and Hyperbaric Medical Society. 10531
Metropolitan Ave., Kensington, MD 20895. (301) 9422980. <http://www.uhms.org>.

Bethany Thivierge

Reconstructive surgery see Plastic, cosmetic,
and reconstructive surgery

Rectal cancer
Definition
The rectum is the portion of the large bowel that
lies in the pelvis, terminating at the anus. Cancer of the
rectum is the disease characterized by the development
of malignant cells in the lining or epithelium of the
rectum. Malignant cells have changed such that they
lose normal control mechanisms governing growth.
These cells may invade surrounding local tissue or
they may spread throughout the body and invade
other organ systems.

Description
The rectum is the continuation of the colon (part
of the large bowel) after it leaves the abdomen and
descends into the pelvis. It is divided into equal thirds:
the upper, mid, and lower rectum.
The pelvis and other organs in the pelvis form
boundaries to the rectum. Behind, or posterior to the
rectum is the sacrum (the lowest portion of the spine,
closest to the pelvis). Laterally, on the sides, the rectum is bounded by soft tissue and bone. In front, the
rectum is bounded by different organs in the male and
female. In the male, the bladder and prostate are present. In the female, the vagina, uterus, and ovaries are
present.
The upper rectum receives its blood supply from
branches of the inferior mesenteric artery from the
abdomen. The lower rectum has blood vessels entering
from the sides of the pelvis. Lymph, a protein-rich
fluid that bathes the cells of the body, is transported
in small channels known as lymphatics. These channels run with the blood supply of the rectum. Lymph
nodes are small filters through which the lymph flows
on its way back to the blood stream. Cancer spreads
elsewhere in the body by invading the lymph and
vascular systems.
When a cell or cells lining the rectum become
malignant, they first grow locally and may invade
GALE ENCYCLOPEDIA OF MEDICINE

By the time the primary tumor is originally
detected, it is usually larger than 1 cm (about 0.39 in)
in size and has over one million cells. This amount of
growth is estimated to take about three to seven years.
Each time the cells double in number, the size of the
tumor quadruples. Thus like most cancers, the part that
is identified clinically is later in the progression than
would be desired. Screening becomes a very important
endeavor to aid in earlier detection of this disease.
Passage of red blood with the stool, (noticeable
bleeding with defecation), is much more common in
rectal cancer than that originating in the colon because
the tumor is much closer to the anus. Other symptoms
(constipation and/ or diarrhea) are caused by obstruction and, less often, by local invasion of the tumor into
pelvic organs or the sacrum. When the tumor has
spread to distant sites, these metastases may cause
dysfunction of the organ they have spread to.
Distant metastasis usually occurs in the liver, less
often to the lung(s), and rarely to the brain.
There are about 36,500 cases of rectal cancer diagnosed per year in the United States. Together, colon
and rectal cancers account for 10% of cancers in men
and 11% of cancers in women. It is the second most
common site-specific cancer affecting both men and
women. Nearly 57,000 people died from colon and
rectal cancer in the United States in 2003. In recent
years the incidence of this disease is decreasing very
slightly, as has the mortality rate. It is difficult to tell if
the decrease in mortality reflects earlier diagnosis, less
death related to the actual treatment of the disease, or
a combination of both factors.
Cancer of the rectum is felt to arise sporadically in
about 80% of those who develop the disease. About
GALE ENCYCLOPEDIA OF MEDICINE

20% of cases probably arise from genetic predisposition; some people have a family history of rectal cancer occurring in a first-degree relative. Development of
rectal cancer at an early age suggests a genetically
transmitted form of the disease as opposed to the
sporadic form.

Causes and symptoms
Causes of rectal cancer are probably environmental in sporadic cases (80%), and genetic in the heredity-predisposed (20%) cases. Since malignant cells
have a changed genetic makeup, this means that in
80% of cases, the environment spontaneously induces
change. Those born with a genetic predisposition are
either destined to get the cancer, or it will take less
environmental exposure to induce the cancer.
Exposure to agents in the environment that may
induce mutation is the process of carcinogenesis and
is caused by agents known as carcinogens. Specific
carcinogens have been difficult to identify; dietary
factors, however, seem to be involved.
Rectal cancer is more common in industrialized
nations. Dietary factors may be the reason. Diets high
in fat, red meat, total calories, and alcohol seem to add
to increased risk. Diets high in fiber are associated
with a decreased risk. High-fiber diets may be related
to less exposure of the rectal epithelium to carcinogens
from the environment as the transit time through the
bowel is faster with a high-fiber diet than with a lowfiber diet.
Age plays a definite role in rectal cancer risk.
Rectal cancer is rare before age 40. This incidence
increases substantially after age 50 and doubles with
each succeeding decade.
There also is a slight increase of risk for rectal
cancer in the individual who smokes.
Patients who suffer from an inflammatory disease
of the colon known as ulcerative colitis are also at
increased risk.
On chromosome 5 is the APC gene associated
with familial adenomatous polyposis (FAP) syndrome. There are multiple mutations that occur at
this site, yet they all cause a defect in tumor suppression that results in early and frequent development of
colon cancer. This is transmitted to 50% of offspring
and each of those affected will develop colon or rectal
cancer, usually at an early age. Another syndrome,
hereditary non-polyposis colon cancer (HNPCC), is
related to mutations in any of four genes responsible
for DNA mismatch repair. In patients with colon or
rectal cancer, the p53 gene is mutated 70% of the time.
3157

Rectal cancer

partially or totally through the wall of the rectum. The
tumor here may invade surrounding tissue or the
organs that bound it, a process known as local invasion. In this process, the tumor penetrates and may
invade the lymphatics or the capillaries locally and
gain access to the circulation in this way. As the malignant cells work their way to other areas of the body,
they again become locally invasive in the new area to
which they have spread. These tumor deposits, originating in the primary tumor in the rectum, are then
known as metastasis. If metastases are found in the
regional lymph nodes, they are known as regional
metastases. If they are distant from the primary
tumor, they are known as distant metastases. The
patient with distant metastases may have widespread
disease, also referred to as systemic disease. Thus the
cancer originating in the rectum begins locally and,
given time, may become systemic.

Rectal cancer

When the p53 gene is mutated and ineffective, cells
with damaged DNA escape repair or destruction,
allowing the damaged cell to multiply. Continued
replication of the damaged DNA may lead to tumor
development. Though these syndromes (FAP and
HNPCC) have a very high incidence of colon or rectal
cancer, family history without the syndromes is also a
substantial risk factor. When considering first-degree
relatives, history of one with colon or rectal cancer
raises the baseline risk from 2% to 6%; the presence of
a second raises the risk to 17%.
The development of polyps of the colon or rectum
commonly precedes the development of rectal cancer.
Polyps are growths of the rectal lining. They can be
unrelated to cancer, pre-cancerous, or malignant.
Polyps, when identified, are removed for diagnosis. If
the polyp, or polyps, are benign, the patient should
undergo careful surveillance for the development of
more polyps or the development of colon or rectal
cancer.
Symptoms of rectal cancer most often result from
the local presence of the tumor and its capacity to
invade surrounding pelvic structure:


bright red blood present with stool



abdominal distention (stretching from internal pressure), bloating, inability to have a bowel movement



narrowing of the stool, so-called ribbon stools



pelvic pain



unexplained weight loss



persistent chronic fatigue



rarely, urinary infection or passage of air in urine in
males (late symptom)



rarely, passage of feces through vagina in females(late symptom)

If the tumor is large and obstructing the rectum,
the patient will not be evacuating stool normally and
will get bloated and have abdominal discomfort. The
tumor itself may bleed and, since it is near the anus,
the patient may see bright red blood on the surface of
the stool. Blood alone (without stool) may also be
passed. Thus, hemorrhoids are often incorrectly
blamed for bleeding, delaying the diagnosis. If anemia develops, which is rare, the patient will experience chronic fatigue. If the tumor invades the bladder
in the male or the vagina in the female, stool will get
where it does not belong and cause infection or discharge. (This condition is also rare.) Patients with
widespread disease lose weight secondary to the
chronic illness.
3158

Diagnosis
Screening evaluation of the colon and rectum are
accomplished together. Screening involves physical
exam, simple laboratory tests, and the visualization
of the lining of the rectum and colon. X rays (indirect
visualization) and endoscopy (direct visualization) are
used to visualize the organs’ lining.
The physical examination involves the performance of a digital rectal exam (DRE). At the time of
this exam, the physician checks the stool on the examining glove with a chemical to see if any occult (invisible), blood is present. At home, after having a bowel
movement, the patient is asked to swipe a sample of
stool obtained with a small stick on a card. After three
such specimens are on the card, the card is then easily
chemically tested for occult blood. These exams are
accomplished as an easy part of a routine yearly physical exam.
Proteins are sometimes produced by cancers and
these may be elevated in the patients blood. When this
occurs the protein produced is known as a tumor
marker. There is a tumor marker for cancer of the
colon and rectum; it is known as carcinoembryonic
antigen, (CEA). Unfortunately, this may be made by
other adenocarcinomas as well, or it may not be produced by a particular colon or rectal cancer.
Therefore, screening by chemical analysis for CEA
has not been helpful. CEA has been helpful in patients
treated for colon or rectal cancer if their tumor makes
the protein. It is used in a follow-up role, not a screening role.
Direct visualization of the lining of the rectum is
accomplished using a scope or endoscope. The physician introduces the instrument into the rectum and is
able to see the epithelium of the rectum directly. A
simple rigid tubular scope may be used to see the rectal
epithelium; however, screening of the colon is done at
the same time. The lower colon may be visualized
using a fiberoptic flexible scope in a procedure
known as flexible sigmoidoscopy. When the entire
colon is visualized, the procedure is known as total
colonoscopy. Each type of endoscopy requires preprocedure preparation (evacuation) of the rectum
and colon.
The American Cancer Society has recommended
the following screening protocol for colon and rectal
cancers those over age 50:


yearly fecal occult blood test



flexible sigmoidoscopy at age 50



flexible sigmoidoscopy repeated every 5 years
GALE ENCYCLOPEDIA OF MEDICINE

double contrast barium enema every five years



colonoscopy every 10 years

If there are predisposing factors such as positive
family history, history of polyps, or a familial syndrome, screening evaluations should start sooner.
Evaluation of patients with symptoms
When patients visit their physician because they
are experiencing symptoms that could possibly be
related to colon or rectal cancer, the entire colon and
rectum must be visualized. Even if a rectal lesion is
identified, the entire colon must be screened to rule out
a syndromous polyp or cancer of the colon. The combination of a flexible sigmoidoscopy and double contrast barium enema may be performed, but the much
preferred evaluation of the entire colon and rectum is
that of complete colonoscopy. Colonoscopy allows
direct visualization, photography, as well as the
opportunity to obtain a biopsy, (a sample of tissue),
of any abnormality visualized. If, for technical reasons
the entire colon is not visualized endoscopically, a
double contrast barium enema should complement
the colonoscopy. A patient who is identified to have
a problem in one area of the colon or rectum is at
greater risk to have a similar problem in area of the
colon or rectum. Therefore the entire colon and rectum need to be visualized during the evaluation.
The diagnosis of rectal cancer is actually made
by the performance of a biopsy of any abnormal
lesion in the rectum. Many rectal cancers are within
reach of the examiner’s finger. Identifying how close
to the anus the cancer has developed is very important in planning the treatment. Another characteristic ascertained by exam is whether the tumor is
mobile or fixed to surrounding structure. Again,
this will have implications related to primary treatment. As a general rule, it is easier to identify and
adequately obtain tissue for evaluation in the rectum
as opposed to the colon. This is because the lesion is
closer to the anus.
If the patient has advanced disease, areas where
the tumor has spread, such as the liver, may require
biopsy. Such biopsies are usually obtained using a
special needle under local anesthesia.
Once a diagnosis of rectal cancer has been established by biopsy, in addition to the physical exam, an
endorectal ultrasound will be performed to assess the
extent of the disease. For rectal cancer, endorectal
ultrasound is the most preferred method for staging
both depth of tumor penetration and local lymph node
status. Endorectal ultrasound:
GALE ENCYCLOPEDIA OF MEDICINE



differentiates areas of invasion within large rectal
adenomas that seem benign



determines the depth of tumor penetration into the
rectal wall



determines the extent of regional lymph node
invasion



can be combined with other tests (chest x rays and
computed tomography scans, or CT scans) to determine the extent of cancer spread to distant organs,
such as the lungs or liver

The resulting rectal cancer staging allows physicians to determine the need for—and order of—radiation, surgery, and chemotherapy. In 2003, it was
reported that magnetic resonance imaging (MRI) also
may be useful in staging rectal cancer. MRI may help
physicians determine if a tumor can be resected and
risk of cancer recurrence.

Treatment
Once the diagnosis has been confirmed by biopsy
and the endorectal ultrasound has been performed, the
clinical stage of the cancer is assigned. The treating
physicians use staging to plan the specific treatment
protocol for the patient. In addition, the stage of the
cancer at the time of presentation gives a statistical
likelihood of the treatment outcome (prognosis).
Clinical staging
Rectal cancer first invades locally and then progresses to spread to regional lymph nodes or to other
organs. Stage is derived using the characteristics of the
primary tumor, its depth of penetration through
the rectum, local invasion into pelvic structure, and
the presence or absence of regional or distant metastases. A CT scan of the pelvis is helpful in staging
because tumor invasion into the sacrum or pelvic sidewalls may mean surgical therapy is not initially possible. On this basis, clinical staging is used to begin
treatment. The pathologic stage is defined when the
results of analyzing the surgical specimen are available. (typically stage I and II).
Rectal cancer is assigned stages I through IV,
based on the following general criteria:


Stage I: the tumor is confined to the epithelium or
has not penetrated through the first layer of muscle
in the rectal wall.



Stage II: the tumor has penetrated through to the
outer wall of the rectum or has gone through it,
possibly invading other local tissue or organs.
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Rectal cancer



Rectal cancer



Stage III: Any depth or size of tumor associated with
regional lymph node involvement.



Stage IV: any of previous criteria associated with
distant metastasis.
Surgery

The first, or primary, treatment modality utilized
in the treatment of rectal cancer is surgery. Stage I, II,
and even suspected stage III disease are treated by
surgical removal of the involved section of the rectum
along with the complete vascular and lymphatic supply. Most Stage II and Stage III rectal cancers (based
on endorectal ultrasound, CT scan, and chest x ray)
are treated with radiation and possibly chemotherapy
prior to surgery.
When determining primary treatment for rectal
cancer, the surgeon’s ability to reconnect the ends of
the rectum. The pelvis is a confining space that makes
the performance of the hook-up more difficult to do
safely when the tumor is in the lower rectum. The
upper rectum does not usually present a substantial
problem to the surgeon restoring bowel continuity
after the cancer has been removed. Mid-rectal tumors,
(especially in males where the pelvis is usually smaller
than a woman’s), may present technical difficulties in
hooking the proximal bowel to the remaining rectum.
Technical advances in stapling instrumentation have
largely overcome these difficulties. If the anastomosis
(hook-up) leaks postoperatively, infection can occur.
In the past, this was a major cause of complications in
resection of rectal cancers. Today, utilizing the stapling instrumentation, a hook-up at the time of original surgery is much safer. If the surgeon feels that the
hook-up is compromised or may leak, a colostomy
may be performed. A colostomy is performed by
bringing the colon through the abdominal wall and
sewing it to the skin. In these cases the stool is diverted
away from the hook-up, allowing it to heal and preventing the infectious complications associated with
leak. Later, when the hook-up has completely healed,
the colostomy can be taken down and bowel continuity restored.
Stapling devices have allowed the surgeon to get
closer to the anus and still allow the technical performance of a hook-up, but there are limits. It is generally
felt that there should be at least three centimeters of
normal rectum below the tumor or the risk of recurrence locally will be excessive. In addition, if there is no
residual native rectum, the patient will not have normal sensation or control and will have problems with
uncontrollable soilage, (incontinence). For these reasons, patients presenting with low rectal tumors may
3160

undergo total removal of the rectum and anus. This
procedure is known as an abdominal-perineal resection. A permanent colostomy is performed in the
lower left abdomen.
Radiation
As mentioned, for many late stage II or stage III
tumors, radiation therapy can shrink the tumor prior
to surgery. The other roles for radiation therapy are
as an aid to surgical therapy in locally advanced
disease that has been removed, and in the treatment
of certain distant metastases. Especially when utilized in combination with chemotherapy, radiation
used postoperatively has been shown to reduce the
risk of local recurrence in the pelvis by 46% and
death rates by 29%. Such combined therapy is
recommended in patients with locally advanced primary tumors that have been removed surgically.
Radiation has been helpful in treating effects of distant metastases, particularly in the brain. In very few
cases, radiation alone may be the curative treatment
for rectal cancer.
Chemotherapy
Adjuvant chemotherapy, (treating the patient
who has no evidence of residual disease but who is at
high risk for recurrence), is considered in patients
whose tumors deeply penetrate or locally invade (late
stage II and stage III). If the tumor was not locally
advanced, this form of chemotherapeutic adjuvant
therapy may be recommended without radiation.
This therapy is identical to that of colon cancer and
leads to similar results. Standard therapy is treatment
with 5-fluorouracil, (5-FU) combined with leucovorin
for a period of six to 12 months. 5-FU is an antimetabolite and leucovorin improves the response rate.
Another agent, levamisole, (which seems to stimulate
the immune system), may be substituted for leucovorin. These protocols reduce rate of recurrence by
about 15% and reduce mortality by about 10%. The
regimens have some toxicity but usually are tolerated
fairly well.
Similar chemotherapy is administered for stage
IV disease or if a cancer progresses and metastasis
develops. Results show response rates of about 20%.
A response is a temporary regression of the cancer in
response to the chemotherapy. Unfortunately, these
patients eventually succumb to the disease. Clinical
trials have now shown that the results can be
improved with the addition of another agent to this
regimen. Irinotecan does not seem to increase toxicity but has improved response rates to 39%, added
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
Most alternative therapies have not been studied
in clinical trials. Large doses of vitamins, fiber, and
green tea are among therapies tried. A 2003 report on a
large Harvard University study showed that people
who took multivitamins for at least 15 years had a
34% reduction in risk of rectal cancer. Before initiating any alternative therapies, the patient should consult his or her physician to be sure that these therapies
do not complicate or interfere with the recommended
therapy.

Prognosis
Prognosis is the long-term outlook or survival
after therapy. Overall, about 50% of patients treated
for colon and rectal cancer survive the disease. As
expected, the survival rates are dependent upon the
stage of the cancer at the time of diagnosis, making
early detection crucial.
About 15% of patients present with stage I disease, or are diagnosed with Stage I disease when they
initially visit a doctor, and 85-90% survive. Stage II
represents 20-30% of cases and 65-75% survive; 3040% comprise the stage III presentation, of which
55% survive. The remaining 20-25% present with
stage IV disease and are rarely cured.

Prevention
There is not an absolute method for preventing
colon or rectal cancer. An individual can lessen risk
or identify the precursors of colon and rectal cancer.
The patient with a familial history can enter screening and surveillance programs earlier than the general population. High-fiber diets and vitamins,
avoiding obesity, and staying active lessen the risk.
In fact, a 2003 report said that vigorous exercise (to
the point of sweating or feeling out of breath) lowered risk of rectal cancer by nearly 40% compared to
those who exercised less. Avoiding cigarettes and
alcohol may be helpful. By controlling these environmental factors, an individual can lessen risk and to
this degree prevent the disease.
By undergoing appropriate screening when
uncontrollable genetic risk factors have been identified, an individual may be rewarded by the identification of benign polyps that can be treated as opposed
GALE ENCYCLOPEDIA OF MEDICINE

Rectal cancer

two to three months to disease free survival, and
prolonged overall survival by a little more than two
months.

KEY TERMS
Adenocarcinoma—Type of cancer beginning in
glandular epithelium.
Adjuvant therapy—Treatment involving radiation,
chemotherapy (drug treatment), or hormone therapy, or a combination of all three given after the
primary treatment for the possibility of residual
microscopic disease.
Anastomosis—Surgical re-connection of the ends
of the bowel after removal of a portion of the
bowel.
Anemia—The condition caused by too few circulating red blood cells, often manifest in part by
fatigue.
Carcinogens—Substances in the environment that
cause cancer, presumably by inducing mutations,
with prolonged exposure.
Defecation—The act of having a bowel movement.
Epithelium—Cells composing the lining of an
organ.
Lymphatics—Channels that are conduits for
lymph.
Lymph nodes—Cellular filters through which lymphatics flow.
Malignant—Cells that have been altered such that
they have lost normal control mechanisms and are
capable of local invasion and spread to other areas
of the body.
Metastasis—Site of invasive tumor growth that
originated from a malignancy elsewhere in the
body.
Mutation—A change in the genetic makeup of a
cell that may occur spontaneously or be environmentally induced.
Occult blood—Presence of blood that cannot be
appreciated visually.
Polyps—Localized growths of the epithelium that
can be benign, pre-cancerous, or harbor
malignancy.
Resect—To remove surgically.
Sacrum—Posterior bony wall of the pelvis.
Systemic—Referring to throughout the body.

to having these
malignancy.

growths

degenerate

into

a

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Rectal examination

Purpose

Resources
BOOKS

Abelhoff, Martin, MD, James O. Armitage MD, Allen S.
Lichter MD, and John E. Niederhuber MD. Clinical
Oncology Library. Philadelphia: Churchill Livingstone,
1999.
Jorde, Lynn B., PhD, John C. Carey MD, Michael J.
Bamshad MD, and Raymond L. White, PhD. Medical
Genetics. 2nd ed. St. Louis: Mosby, 1999.
PERIODICALS

‘‘Colon Cancer; Facts to Know.’’ NWHRC Health Center
December 15, 2003.
‘‘Endoscopy and MRI Are Important in Staging Rectal
Cancer.’’ Clinical Oncology Week October 6, 2003: 56.
Greenlee, Robert T., PhD, MPH, Mary Beth Hill-Harmon,
MSPH, Taylor Murray, and Michael Thun, MD, MS.
‘‘Cancer Statistics 2001.’’ CA: A Cancer Journal for
Clinicians, 51, no. 1 (January-February 2001).
Saltz, Leonard, et al. ‘‘Irinotecan plus Fluorouracil and
Leucovorin for Metastatic Colorectal Cancer.’’ The
New England Journal of Medicine 343, no. 13
(September 28, 2000).
Splete, Heidi. ‘‘Multivitamins May Lower Risk of Rectal
Cancer: Drops 34% at 15 Years.’’ Family Practice News
December 1, 2003: 33.
‘‘Vigourous Physical Activity May Reduce the Risk of Rectal
Cancer.’’ Environmental Nutrition October 2003: 8.
ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800)ACS-2345. Lt;http://
www.cancer.org>.
Cancer Information Service of the NCI. 9000 Rockville Pike,
Building 31, Suite 10A18, Bethesda, MD 20892. (800) 4CANCER. <http://wwwicic.nci.nih.gov>.
OTHER

Colon Cancer Alliance. <http://www.ccalliance.org>.
National Cancer Institute Clinical Trials. <http://
www.cancertrials.nci.nih.gov>.

Richard A. McCartney, MD
Teresa G. Odle

DRE is used as a screening tool to locate rectal
cancer and prostate cancer. It is also used as a diagnostic test to find non-cancerous abnormalities within
the rectum like hemorrhoids, anal fissures, or congenital deformities that can cause chronic constipation.

Precautions
There are no precautions when performing DRE,
aside from routine sanitary procedures.

Description
DRE is performed in most instances as an annual
routine procedure in colorectal cancer screening.
Digital palpitation of the rectum can often find abnormal growths which may require further testing or
commonplace hemorrhoids. It is a critical initial clinical test and is important in the assessment of the size
and location of tumors.
This procedure is often not performed routinely
on patients over 70, even though this population is at
high risk for colorectal cancer. It also is not done as
often in elderly women as in elderly men.
DRE has also been used as a screening tool for
prostate cancer. It seems to be very effective for larger
masses found in the prostate and correlated well with
higher prostate-specific antigens.
Of less predictive value was DRE in routine rectovaginal examinations of women under the age of 50.
These instances of DRE did not locate colorectal cancer or any other abnormality.
More gastroenterologists are recommending that
pediatricians and family physicians perform DRE on
pediatric patients exhibiting chronic constipation
before those patients are referred to intestinal specialists. The pediatrician or family physician could identify fecal compaction and treat it themselves, and then
only refer patients who have a specific abnormality to
gastroenterologists.

Preparation

Rectal examination
Definition
Rectal examination or digital rectal examination
(DRE) is performed by means of inserting a gloved,
lubricated finger into the rectum and palpating (feeling) for lumps.
3162

The physician must conduct DRE using a gloved
hand. Some sort of lubricant should be used so that
penetration of the rectum is easier and does not create
the damage that the procedure is seeking.

Aftercare
There is no aftercare after a DRE is performed.
GALE ENCYCLOPEDIA OF MEDICINE

DRE—Digital rectal examination.
Gastroenterologist—A physician who specializes
in diseases of the digestive system.
Rectum—The last eight to ten inches of the colon,
of which the anus is a part and the opening through
which wastes are removed from the body.

Risks
There are no risks to DRE and it is virtually
painless.

Normal results

The rectum is the last segment of the large intestine, ending in the anus, the opening to the exterior of
the body. Rectal polyps are quite common. They occur
in 7–50% of all people, and in two thirds of people
over age 60.
Rectal polyps can be either benign or malignant,
large or small. There are several different types of
polyps. The type is determined by taking a sample
of the polyp and examining it microscopically. Most
polyps are benign. They are of concern, however,
because 90% of colon and rectal cancers arise from
polyps that are initially benign. For this reason, rectal polyps are usually removed when they are
discovered.

Causes and symptoms

The physician finds a normal rectal canal with no
abnormalities.

Abnormal results
Growths, tears, anal fissures, or congenital structural defects can be found inside the rectum with
DRE.
Resources
PERIODICALS

Kirchner, Jeffrey T.‘‘Digital Rectal Examination in
Children with Constipation.’’ American Family
Physician 60, no. 5 (October 1, 1999): 1530.
Schroder, Fritz H. ‘‘Evaluation of the Digital Rectal
Examination as a Screening Test for Prostate Cancer.’’
JAMA, The Journal of the American Medical
Association 281, no. 7 (February 7, 1999) 594.
OTHER

Practice Parameters for the Treatment of Rectal Carcinoma
American Society of Colon and Rectal Surgeons May 7,
2001. <http://www.asco.org/prof/me/html/abstracts/
gasc/m_969.htm>.

Janie F. Franz

Rectal polyps
Definition
Rectal polyps are tissue growths that arise from
the wall of the rectum and protrude into it. They may
be either benign or malignant (cancerous).
GALE ENCYCLOPEDIA OF MEDICINE

The cause of most rectal polyps is unknown,
however a diet high in animal fat and red meat, and
low in fiber, is thought to encourage polyp formation. Some types of polyps are hereditary. In an
inherited disease called familial polyposis, hundreds
of small, malignant and pre-malignant polyps are
produced before the age of 40. Also, inflammatory
bowel disease may cause growth of polyps and
pseudo-polyps. Juvenile polyps (polyps in children)
are usually benign and often outgrow their blood
supply and disappear at puberty.
Most rectal polyps produce no symptoms and are
discovered on routine digital or endoscopic examination of the rectum. Rectal bleeding is the most common complaint when symptoms do occur. Abdominal
cramps, pain, or obstruction of the intestine occur with
some large polyps. Certain types of polyps cause
mucous-filled or watery diarrhea.

Diagnosis
Rectal polyps are commonly found by sigmoidoscopy (visual inspection with an instrument consisting
of a tube and a light) or colonoscopy. If polyps are
found in the rectum, a complete examination of the
large intestine is done, as multiple polyps are common.
Polyps do not show up on regular x rays, but they do
appear on barium enema x rays.

Treatment
Normally polyps are removed when they are
found. Polypectomy is the name for the surgery that
removes these growths. Polypectomy is performed at a
hospital, outpatient surgical facility or in a doctor’s
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Rectal polyps

Description

KEY TERMS

Rectal prolapse

Prevention

KEY TERMS
Colon—The part of the large intestine that extends
from the cecum to the rectum. The sigmoid colon is
the area of the intestine just above the rectum;
linking the descending colon with the rectum. It is
shaped like the letter S.
Rectum—The final part of the large intestine, ending in the anus.
Sigmoidoscopy—A procedure where a thin tube
containing a camera and a light is inserted into
the lower section of the large intestine so that the
doctor can visually inspect the lower (sigmoid)
colon and rectum. Colonoscopy examines the
entire large intestine using the same techniques.

office, depending on the number and type of polyps to
be removed, and the age and health of the patient. The
procedure can be done by a surgeon, gastroenterologist, or family practitioner.
Before the operation, a colonoscopy (examination
of the intestine with an endoscope) is performed, and
standard pre-operative blood and urine studies are
done. The patient is also given medicated enemas to
cleanse the bowel.
The patient is given a sedative and a narcotic
pain killer. A colonoscope is inserted into the rectum.
The polyps are located and removed with a wire
snare, ultrasound, or laser beam. After they are
removed, the polyps are examined to determine if
they are malignant or benign. When polyps are
malignant, it may be necessary to remove a portion
of the rectum or colon to completely remove cancerous tissue.

Alternative treatment
In addition to a diet low in animal fat and high in
fiber, nutritionists recommend anitoxidant supplements (including vitamins A, C, and E, selenium, and
zinc) to reduce rectal polyps.

Prognosis
For most people, the removal of polyps is an
uncomplicated procedure. Benign polyps that are
left in place can give rise to rectal cancer. People who
have had rectal polyps once are more likely to have
them again and should have regular screening
examinations.
3164

Eating a diet low in red meat and animal fat, and
high in fiber, is thought to help prevent rectal polyps.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Tish Davidson, A.M.

Rectal prolapse
Definition
Rectal prolapse is protrusion of rectal tissue
through the anus to the exterior of the body. The
rectum is the final section of the large intestine.

Description
Rectal prolapse can be either partial or complete.
In partial prolapse, only the mucosa layer (mucous
membrane) of the rectum extends outside the body.
The projection is generally 0.75–1.5 in (2–4 cm) long.
In complete prolapse, called procidentia, the full thickness of the rectum protrudes for up to 4.5 in (12 cm).
Rectal prolapse is most common in people over
age 60, and occurs much more frequently in women
than in men. It is also more common in psychiatric
patients. Prolapse can occur in normal infants, where
it is usually transient. In children it is often an early
sign of cystic fibrosis or is due to neurological or
anatomical abnormalities.
Although rectal prolapse in adults may initially
reduce spontaneously after bowel movements, it eventually becomes permanent. Adults who have had prior
rectal or vaginal surgery, who have chronic constipation, regularly depend on laxatives, have multiple
sclerosis or other neurologic diseases, stroke, or
paralysis are more likely to experience rectal prolapse.

Causes and symptoms
Rectal prolapse in adults is caused by a weakening
of the sphincter muscle or ligaments that hold the
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms of rectal prolapse include discharge of
mucus or blood, pain during bowel movements, and
inability to control bowel movements (fecal incontinence). Patients may also feel the mass of tissue protruding from the anus. With large prolapses, the
patient may lose the normal urge to have a bowel
movement.

KEY TERMS
Rectum—The part of the large intestine that ends at
the anal canal.

recover completely without complications. Recovery
in adults depends on age, general health, and the
extent of the prolapse.

Prevention

Diagnosis
Prolapse is initially diagnosed by taking a patient
history and giving a rectal examination while the
patient is in a squatting position. It is confirmed by
sigmoidoscopy (inspection of the colon with a viewing
instrument called a endoscope) Barium enema x rays
and other tests are done to rule out neurologic (nerve)
disorders or disease as the primary cause of prolapse.

Reducing constipation by eating a diet high in
fiber, drinking plenty of fluids, and avoiding straining
during bowel movements help prevent the onset of
prolapse. Exercises that strengthen the anal sphincter
may also be helpful.
Resources
OTHER

Treatment
In infants, conservative treatment, consisting of
strapping the buttocks together between bowel movements and eliminating any causes of bowel straining,
usually produces a spontaneous resolution of prolapse. For partial prolapse in adults, excess tissue is
surgically tied off with special bands causing the tissue
to wither in a few days.
Complete prolapse requires surgery. Different
surgical techniques are used, but all involve anchoring
the rectum to other parts of the body, and using plastic
mesh to reinforce and support the rectum. In patients
too old, or ill, to tolerate surgery, a wire or plastic loop
can be inserted to hold the sphincter closed and prevent prolapse. Treatment should be undertaken as
soon as prolapse is diagnosed, since the longer the
condition exists, the more difficult it is to reverse.

Alternative treatment
Alternative therapies can act as support for conventional threatment, especially if surgery is required.
Acupuncture, homeopathy, and botanical medicine
can all be used to assist in resolution of the prolapse
or in recovery from surgery.

Prognosis
Successful resolution of rectal prolapse involves
prompt treatment and the elimination of any underlying causes of prolapse. Infants and children usually
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Rectal Prolapse.’’ ThriveOnline. <http://
thriveonline.oxygen.com>.

Tish Davidson, A.M.

Recurrent fever see Relapsing fever

Recurrent miscarriage
Definition
Recurrent miscarriage is defined as three or more
miscarriages of a fetus before 20 weeks of gestation
(i.e., before the fetus can live outside the womb).

Description
Also referred to as spontaneous abortion, miscarriage occurs in 15–20% of all conceptions. The majority of miscarriages occur during the first trimester. The
number of previous miscarriages does not affect subsequent full-term pregnancies.

Causes and symptoms
Recurrent miscarriage can be caused by several
factors, including fetal, placental, or maternal
abnormalities.


In over half of all miscarriages, the fetus is abnormal.
The abnormality can either be genetic or
3165

Recurrent miscarriage

rectum in place. Weakening can occur because of
aging, disease, or in rare cases, surgical trauma.
Prolapse is brought on by straining to have bowel
movements, chronic laxative use, or severe diarrhea.

Red blood cell indices

developmental. The fetus is very sensitive to ionizing
radiation. Tobacco and even moderate alcohol consumption are known to cause fetal damage that may
lead to miscarriage. There is some evidence that over
four cups of coffee a day, because of the caffeine,
adversely affect pregnancy, as well.






Placental abnormalities, including abnormal implantation in the placental wall and premature separation
of the placenta, can cause miscarriage.
Maternal abnormalities include insufficient hormones (usually progesterone) to support the pregnancy, an incompetent cervix (mouth of the womb
does not stay closed), or a deformed uterus (womb).
A deformed uterus can be caused by diethylstilbestrol (DES) given to the mother’s mother during her
pregnancy. Some immunologic abnormalities may
cause the mother to reject the fetus as if it were an
infection or a transplant. Maternal blood clotting
abnormalities may cut-off blood supply to the
fetus, causing miscarriage.
Maternal diabetes mellitus causes miscarriage if the
diabetes is poorly controlled. Maternal infections
may occasionally lead to miscarriage. There is some
evidence that conceptions that take place between
old eggs (several days after ovulation) or old sperm
(that start out several days before ovulation) may be
more likely to miscarry.

Symptoms of miscarriage include pink or brown
colored discharge for several weeks, which develops
into painful cramping and increased vaginal bleeding;
dilation of the cervix; and expulsion of the fetus.

KEY TERMS
Fetus—A developing embryo in the womb after the
first eight weeks of gestation.
Ionizing radiation—Radiation produced by x rays
and radioactivity.
Ovulation—Release of an egg for fertilization from
the ovary that happens about fourteen days before
each menstrual period.

miscarriage. Clotting abnormalities can be treated
with anticoagulant drugs, such as heparin and aspirin,
to keep blood flowing to the fetus.

Prognosis
If there is no underlying disease or abnormality
present, the rate of successful pregnancy after several
miscarriages approaches normal. Seventy to eightyfive percent of women with three or more miscarriages
will go on to complete a healthy pregnancy.
Resources
BOOKS

Cunningham, F. Gary, et al., editor. Williams Obstetrics.
Stamford: Appleton & Lange, 1997.

J. Ricker Polsdorfer, MD

Diagnosis
A pelvic examination can detect a deformed
uterus, and frequent examinations during pregnancy
can detect an incompetent cervix. Blood tests can
detect the presence of immunologic or blood-clotting
problems in the mother. Genetic testing can also determine if chromosomal abnormalities may be causing
the miscarriages.

Treatment
If a uterus is deformed, it may be surgically
repaired. If a cervix is incompetent, it can be surgically
fortified, until the fetus matures, by a procedure
known as circlage (tying the cervix closed).
Supplemental progesterone may also help sustain a
pregnancy. Experimental treatment of maternal
immunologic abnormalities with white cell immunization (injecting the mother with white cells from the
father) has been successful in some cases of recurrent
3166

Red blood cell indices
Definition
Red blood cell indices are measurements that
describe the size and oxygen-carrying protein (hemoglobin) content of red blood cells. The indices are used
to help in the differential diagnosis of anemia. They
are also called red cell absolute values or erythrocyte
indices.

Purpose
Anemia includes a variety of conditions with the
same outcome: a person’s blood cannot carry as much
oxygen as it should. A healthy person has an adequate
number of correctly sized red blood cells that contain
enough hemoglobin to carry sufficient oxygen to all
GALE ENCYCLOPEDIA OF MEDICINE

Anemia is caused by many different diseases or
disorders. The first step in finding the cause is to
determine what type of anemia the person has. Red
blood cell indices help to classify the anemias.

Precautions
Certain prescription medications may affect the
test results. These drugs include zidovudine
(Retrovir), phenytoin (Dilantin), and azathioprine
(Imuran).

Description
Overview
Anemia has several general causes: blood loss; a
drop in production of red blood cells; or a rise in the
number of red blood cells destroyed. Blood loss can
result from severe hemorrhage or a chronic slow bleed,
such as the result of an accident or an ulcer. Lack of
iron, vitamin B12, or folic acid in the diet, as well as
certain chronic diseases, lower the number of red
blood cells produced by the bone marrow. Inherited
disorders affecting hemoglobin, severe reactions to
blood transfusions, prescription medications, or poisons can cause red blood cells to burst (hemolyze) well
before the end of their usual 120-day lifespan.
Anemia of any type affects the results of one or
more of the common blood tests. These tests are the
hematocrit, hemoglobin, and red blood cell count. The
hematocrit is a measure of red blood cell mass, or how
much space in the blood is occupied by red blood cells.
The hemoglobin test is a measure of how much hemoglobin protein is in the blood. The red blood cell count
(RBC) measures the number of red blood cells present
in the blood. Red blood cell indices are additional
measurements of red blood cells based on the relationship of these three test results.
The relationships between the hematocrit, the
hemoglobin level, and the RBC are converted to red
blood cell indices through mathematical formulas.
These formulas were worked out and first applied to
the classification of anemias by Maxwell Wintrobe
in 1934.
The indices include these measurements: mean
corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean corpuscular hemoglobin
GALE ENCYCLOPEDIA OF MEDICINE

concentration (MCHC); and red cell distribution
width (RDW). They are usually calculated by an automated instrument as part of a complete blood count
(CBC). Indices are covered by insurance when medically necessary. Results are available the same day that
the blood is drawn or the following day.
Mean corpuscular volume (MCV)
MCV is the index most often used. It measures the
average volume of a red blood cell by dividing the
hematocrit by the RBC. The MCV categorizes red
blood cells by size. Cells of normal size are called
normocytic, smaller cells are microcytic, and larger
cells are macrocytic. These size categories are used to
classify anemias. Normocytic anemias have normalsized cells and a normal MCV; microcytic anemias
have small cells and a decreased MCV; and macrocytic
anemias have large cells and an increased MCV.
Under a microscope, stained red blood cells with a
high MCV appear larger than cells with a normal or
low MCV.
Mean corpuscular hemoglobin concentration
(MCHC)
The MCHC measures the average concentration
of hemoglobin in a red blood cell. This index is calculated by dividing the hemoglobin by the hematocrit.
The MCHC categorizes red blood cells according to
their concentration of hemoglobin. Cells with a normal concentration of hemoglobin are called normochromic; cells with a lower than normal concentration
are called hypochromic. Because there is a physical
limit to the amount of hemoglobin that can fit in a
cell, there is no hyperchromic category.
Just as MCV relates to the size of the cells, MCHC
relates to the color of the cells. Hemoglobin contains
iron, which gives blood its characteristic red color.
When examined under a microscope, normal red
blood cells that contain a normal amount of hemoglobin stain pinkish red with a paler area in the center.
These normochromic cells have a normal MCHC.
Cells with too little hemoglobin are lighter in color
with a larger pale area in the center. These hypochromic cells have a low MCHC. Anemias are categorized
as hypochromic or normochromic according to the
MCHC index.
Mean corpuscular hemoglobin (MCH)
The average weight of hemoglobin in a red blood
cell is measured by the MCH. The formula for this
index is the sum of the hemoglobin multiplied by 10
3167

Red blood cell indices

the body’s tissues. An anemic person has red blood
cells that are either too small or too few in number. As
a result, the heart and lungs must work harder to make
up for the lack of oxygen delivered to the tissues by the
blood.

Red blood cell indices

and divided by the RBC. MCH values usually rise or
fall as the MCV is increased or decreased.
Red cell distribution width (RDW)
The RDW measures the variation in size of the red
blood cells. Usually red blood cells are a standard size.
Certain disorders, however, cause a significant variation in cell size.
Obtaining the blood sample
The RBC indices test requires 0.17–24 oz (5–7 ml)
of blood. A healthcare worker ties a tourniquet on the
person’s upper arm, locates a vein in the inner elbow
region, and inserts a needle into that vein. Vacuum
action draws the blood through the needle into an
attached tube. Collection of the sample takes only a
few minutes.

Preparation
The doctor should check to see if the patient is
taking any medications that may affect test results.
The patient does not need to fast before the test.

Aftercare
Aftercare consists of routine care of the area
around the puncture mark. Pressure is applied for a
few seconds and the wound is covered with a bandage.

Risks
The primary risk is mild dizziness and the possibility of a bruise or swelling in the area where the blood
was drawn. The patient can apply moist warm
compresses.

Normal results
Normal results for red blood cell indices are as
follows:


MCV 82–98 fl (femtoliters)



MCHC 31–37 g/dl



MCH 26–34 pg (picograms)



RDW 11.5–14.5%.

Abnormal results
The category into which a person’s anemia is
placed based on the indices provides a significant
clue as to the cause of the anemia, but further testing
is needed to confirm a specific diagnosis.
3168

KEY TERMS
Anemia—A variety of conditions in which a person’s blood can’t carry as much oxygen as it should
due to a decreased number or size of red blood
cells.
Hypochromic—A descriptive term applied to a red
blood cell with a decreased concentration of
hemoglobin.
Macrocytic—A descriptive term applied to a larger
than normal red blood cell.
Mean corpuscular hemoglobin (MCH)—A measurement of the average weight of hemoglobin in
a red blood cell.
Mean corpuscular hemoglobin concentration
(MCHC)—The measurement of the average concentration of hemoglobin in a red blood cell.
Mean corpuscular volume (MCV)—A measure of
the average volume of a red blood cell.
Microcytic—A descriptive term applied to a smaller than normal red blood cell.
Normochromic—A descriptive term applied to a
red blood cell with a normal concentration of
hemoglobin.
Normocytic—A descriptive term applied to a red
blood cell of normal size.
Red blood cell indices—Measurements that
describe the size and hemoglobin content of red
blood cells.
Red cell distribution width (RDW)—A measure of
the variation in size of red blood cells.

The most common causes of macrocytic anemia
(high MCV) are vitamin B12 and folic acid deficiencies.
Lack of iron in the diet, thalassemia (a type of hereditary anemia), and chronic illness are the most common
causes of microcytic anemia (low MCV). Normocytic
anemia (normal MCV) can be caused by kidney and
liver disease, bone marrow disorders, or excessive
bleeding or hemolysis of the red blood cells.
Lack of iron in the diet and thalassemia are the
most common causes of hypochromic anemia (low
MCHC). Normocytic anemias are usually also normochromic and share the same causes (normal
MCHC).
The RDW is increased in anemias caused by deficiencies of iron, vitamin B12, or folic acid. Abnormal
hemoglobins, such as in sickle cell anemia, can change
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Atrophy—Abnormal changes in a cell that lead to
loss of cell structure and function.
Osteoporosis—Reduction in the quantity of bone.

Resources
BOOKS

Pagana, Kathleen Deska, and Timothy James Pagana, editors. Mosby’s Manual of Diagnostic and Laboratory
Tests. St. Louis: Mosby, Inc., 1998.

affected, but the number of new cases is higher in
women, adolescents, and young adults. RDS has been
associated with other terms such as Sudeck’s atrophy,
post-traumatic osteoporosis, causalgia, shoulder-hand
syndrome, and reflex neuromuscular dystrophy.

Nancy J. Nordenson

Causes and symptoms

Red blood cell test see Hemoglobin test

Reflex sympathetic dystrophy
Definition
Reflex sympathetic dystrophy is the feeling of pain
associated with evidence of minor nerve injury.

Description
Historically, reflex sympathetic dystrophy (RSD)
was noticed during the civil war in patients who suffered pain following gunshot wounds that affected the
median nerve (a major nerve in the arm). In 1867 the
condition was called causalgia form the Greek term
meaning ‘‘burning pain.’’ Causalgia refers to pain
associated with major nerve injury. The exact causes
of RSD are still unclear. Patients usually develop a
triad of phases. In the first phase, pain and sympathetic activity is increased. Patients will typically present with swelling (edema), stiffness, pain, increased
vascularity (increasing warmth), hyperhydrosis, and
x-ray changes demonstrating loss of minerals in bone
(demineralization). The second phase develops three
to nine months later, It is characterized by increased
stiffness and changes in the extremity that include a
decrease in warmth and atrophy of the skin and muscles. The late phase commencing several months to
years later presents with a pale, cold, painful, and
atrophic extremity. Patients at this stage will also
have osteoporosis.
It has been thought that each phase relates to a
specific nerve defect that involves nerve tracts from the
periphery spinal cord to the brain. Both sexes are
GALE ENCYCLOPEDIA OF MEDICINE

The exact causes of RSD at present is not clearly
understood. There are several theories such as sympathetic overflow (over activity), abnormal circuitry in
nerve impulses through the sympathetic system, and as
a post-operative complication for both elective and
traumatic surgical procedures. Patients typically
develop pain, swelling, temperature, color changes,
and skin and muscle wasting.

Diagnosis
The diagnosis is simple and confirmed by a local
anesthetic block along sympathetic nerve paths in the
hand or foot, depending on whether an arm or leg is
affected. A test called the erythrocyte sedimentation rate
(ESR) can be performed to rule out diseases with similar presentation and arising from other causes.

Treatment
The preferred method to treat RSD includes sympathetic block and physical therapy. Pain is improved
as motion of the affected limb improves. Patients may
also require tranquilizers and mild analgesics. Patients
who received repeated blocks should consider surgical
symathectomy (removal of the nerves causing pain).

Prognosis
The prognosis for treatment during phase one is
favorable. As the disease progresses undetected into
phase two or three the prognosis for recovery is poor.

Prevention
There is no known prevention since the cause is
not clearly understood.
3169

Reflex sympathetic dystrophy

the shape of red blood cells as well as cause them to
hemolyze. The abnormal shape and the cell fragments
resulting from hemolysis increase the RDW.
Conditions that cause more immature cells to be
released into the bloodstream, such as severe blood
loss, will increase the RDW. The larger size of immature cells creates a distinct size variation.

Reflex tests

Resources



biceps

BOOKS



triceps

Goetz, Christopher G., et al, editors. Textbook of Clinical
Neurology. 1st ed. W. B. Saunders Company, 1999.
Ruddy, Shaun, et al, editors. Kelly’s Textbook of
Rheumatology. 6th ed. W. B. Saunders Company, 2001.

Another type of reflex test is called the Babinski
test, which involves gently stroking the sole of the foot
to assess proper development of the spine and cerebral
cortex.

OTHER

Reflex Sympathetic Dystrophy Syndrome Association of
America. <http://www.rsds.org/fact.html>.

Laith Farid Gulli, M.D.
Robert Ramirez, B.S.

Precautions
Reflex tests are entirely safe, and no special precautions are needed.

Description

Reflex tests
Definition
Reflex tests are simple physical tests of nervous
system function.

Purpose
A reflex is a simple nerve circuit. A stimulus, such
as a light tap with a rubber hammer, causes sensory
neurons (nerve cells) to send signals to the spinal
cord. Here, the signals are conveyed both to the
brain and to nerves that control muscles affected by
the stimulus. Without any brain intervention, these
muscles may respond to an appropriate stimulus by
contracting.
Reflex tests measure the presence and strength of
a number of reflexes. In so doing, they help to assess
the integrity of the nerve circuits involved. Reflex tests
are performed as part of a neurological exam, either a
‘‘mini-exam’’ done to quickly confirm integrity of the
spinal cord, or a more complete exam performed to
diagnose the presence and location of spinal cord
injury or neuromuscular disease.
Deep tendon reflexes are responses to muscle
stretch. The familiar ‘‘knee-jerk’’ reflex is an example;
this reflex tests the integrity of the spinal cord in the
lower back region. The usual set of deep tendon
reflexes tested, involving increasingly higher regions
of the spinal cord, are:


ankle



knee



abdomen



forearm

3170

The examiner positions the patient in a comfortable
position, usually seated on the examination table with
legs hanging free. The examiner uses a rubber mallet to
strike different points on the patient’s body, and observes
the response. The examiner may position, or hold, one of
the limbs during testing, and may require exposure of the
ankles, knees, abdomen, and arms. Reflexes can be difficult to elicit if the patient is paying too much attention to
the stimulus. To compensate for this, the patient may be
asked to perform some muscle contraction, such as
clenching teeth or grasping and pulling the two hands
apart. When performing the Babinski reflex test, the
doctor will gently stroke the outer soles of the patient’s
feet with the mallet while checking to see whether or not
the big toe extends out as a result.

Normal results
The strength of the response depends partly on the
strength of the stimulus. For this reason, the examiner
will attempt to elicit the response with the smallest
stimulus possible. Learning the range of normal
responses requires some clinical training. Responses
should be the same for both sides of the body. A
normal response to the Babinski reflex test depends
upon the age of the person being examined. In children
under the age of one and a half years, the big toe will
extend out with or without the other toes. This is due
to the fact that the fibers in the spinal cord and cerebral cortex have not been completely covered in myelin, the protein and lipid sheath that aids in processing
neural signals. In adults and children over the age of
one and a half years, the myelin sheath should be
completely formed, and, as a result, all the toes will
curl under (planter flexion reflex).

Abnormal results
Weak or absent response may indicate damage to
the nerves outside the spinal cord (peripheral
GALE ENCYCLOPEDIA OF MEDICINE

Resources
OTHER

Rathe, Richard. ‘‘The Neurological Exam.’’ A Healthy Me
Page. July 2, 1997. <http://www.ahealthyme.com>.

Richard Robinson

Reflexology
Definition
Reflexology is a therapeutic method of relieving
pain by stimulating predefined pressure points on the
feet and hands. This controlled pressure alleviates the
source of the discomfort. In the absence of any particular malady or abnormality, reflexology may be as
effective for promoting good health and for preventing illness as it may be for relieving symptoms of stress,
injury, and illness.
Reflexologists work from maps of predefined
pressure points that are located on the hands and
feet. These pressure points are reputed to connect
directly through the nervous system and affect the
bodily organs and glands. The reflexologist manipulates the pressure points according to specific techniques of reflexology therapy. By means of this touching
therapy, any part of the body that is the source of pain,
illness, or potential debility can be strengthened
through the application of pressure at the respective
foot or hand location.

Purpose
Reflexology promotes healing by stimulating the
nerves in the body and encouraging the flow of blood.
In the process, reflexology not only quells the sensation of pain, but relieves the source of the pain as well.
Anecdotally, reflexologists claim success in the
treatment of a variety of conditions and injuries. One
GALE ENCYCLOPEDIA OF MEDICINE

E U N I C E I N G H A M (1889–1974)
Eunice D. Ingham was born on February 24, 1889. A
physical therapist by occupation, she was a colleague of
Dr. Shelby Riley, who along with Dr. W. H. Fitzgerald
actively developed zone therapy, a similar but distinct
therapy from reflexology. Unlike reflexology, zone therapy does not connect the zones with the body as a whole.
In the 1930s, Ingham discovered an unmistakable pattern
of reflexes on the human foot; she subsequently devoted
the rest of her life to publicizing the message of reflexology until shortly before her death on December 10, 1974.
Ingham traveled and lectured widely about reflexology, initially to audiences of extremely desperate or aging
patients who had lost hope in finding relief. Because of
their sometimes astonishing improvement, reflexology
became better known and respected among the medical
community and gained credibility for its therapeutic
value. Ingham described her theories of reflexology in
her 1938 book, entitled Stories the Feet Can Tell, which
included a map of the reflex points on the feet and the
organs that they parallel. The book was translated into
seven languages, although it was erroneously published
as Zone Therapy in some countries, an error which led to
misunderstanding about the true nature of reflexology and
inaccurately linked it to zone therapy.

condition is fibromyalgia. People with this disease are
encouraged to undergo reflexology therapy to alleviate any of a number of chronic bowel syndromes
associated with the condition. Frequent brief sessions
of reflexology therapy are also recommended as an
alternative to drug therapy for controlling the muscle
pain associated with fibromyalgia and for relieving
difficult breathing caused by tightness in the muscles
of the patient’s neck and throat.
Reflexology applied properly can alleviate allergy
symptoms, as well as stress, back pain, and chronic
fatigue. The techniques of reflexology can be performed conveniently on the hand in situations where
a session on the feet is not practical, although the
effectiveness of limited hand therapy is less pronounced than with the foot pressure therapy.

Description
Origins
Reflexology is a healing art of ancient origin.
Although its origins are not well documented, there
are reliefs on the walls of a Sixth Dynasty Egyptian
tomb (c. 2450 B.C.) that depict two seated men
3171

Reflexology

neuropathy), damage to the motor neurons just before
or just after they leave the spinal cord (motor neuron
disease), or muscle disease. Excessive response may
indicate spinal cord damage above the level controlling the hyperactive response. Different responses on
the two sides of the body may indicate early onset of
progressive disease, or localized nerve damage, as
from trauma. An adult or older child who responds
to the Babinski with an extended big toe may have a
lesion in the spinal cord or cerebral cortex.

Reflexology

receiving massage on their hands and feet. From Egypt,
the practice may have entered the Western world during
the conquests of the Roman Empire. The concepts of
reflexology have also been traced to pre-dynastic China
(possibly as early as 3000 B.C.) and to ancient Indian
medicine. The Inca civilization may have subscribed to
the theories of reflexology and passed on the practice of
this treatment to the Native Americans in the territories
that eventually entered the United States.
In recent times, Sir Henry Head first investigated
the concepts underlying reflexology in England in the
1890s. Therapists in Germany and Russia were
researching similar notions at approximately the
same time, although with a different focus. Less than
two decades later, a physician named William H.
Fitzgerald presented a similar concept that he called
zone analgesia or zone therapy. Fitzgerald’s zone
analgesia was a method of relieving pain through the
application of pressure to specific locations throughout the entire body. Fitzgerald divided the body into
10 vertical zones, five on each side, that extended from
the head to the fingertips and toes, and from front
toback. Every aspect of the human body appears in
one of these 10 zones, and each zone has a reflex area
on the hands and feet. Fitzgerald and his colleague,
Dr. Edwin Bowers, demonstrated that by applying
pressure on one area of the body, they could anesthetize or reduce pain in a corresponding part. In 1917,
Fitzgerald and Bowers published Relieving Pain at
Home, an explanation of zone therapy.
Later, in the 1930s, a physical therapist, Eunice D.
Ingham, explored the direction of the therapy and
made the startling discovery that pressure points on
the human foot were situated in a mirror image of the
corresponding organs of the body with which the
respective pressure points were associated. Ingham
documented her findings, which formed the basis of
reflexology, in Stories the Feet Can Tell, published in
1938. Although Ingham’s work in reflexology was
inaccurately described as zone therapy by some,
there are differences between the two therapies of
pressure analgesia. Among the more marked differences, reflexology defines a precise correlation
between pressure points and afflicted areas of the
body. Furthermore, Ingham divided each foot and
hand into 12 respective pressure zones, in contrast to
the 10 vertical divisions that encompass the entire
body in Fitzgerald’s zone therapy.
In 1968 two siblings, Dwight Byers and Eusebia
Messenger, established the National Institute of
Reflexology. By the early 1970s the institute had
grown and was renamed the International Institute
of Reflexology.
3172

In a typical reflexology treatment, the therapist
and patient have a preliminary discussion prior to
therapy, to enable the therapist to focus more accurately on the patient’s specific complaints and to determine the appropriate pressure points for treatment.
A reflexology session involves pressure treatment
that is most commonly administered in foot therapy
sessions of approximately 40–45 minutes in duration.
The foot therapy may be followed by a brief 15-minute
hand therapy session. No artificial devices or special
equipment are associated with this therapy. The human
hand is the primary tool used in reflexology. The therapist applies controlled pressure with the thumb and
forefinger, generally working toward the heel of the
foot or the outer palm of the hand. Most reflexologists
apply pressure with their thumbs bent; however, some
also use simple implements, such as the eraser end of a
pencil. Reflexology therapy is not massage, and it is not
a substitute for medical treatment.
Reflexology is a complex system that identifies and
addresses the mass of 7,000 nerve endings that are
contained in the foot. Additional reflexology addresses
the nerves that are located in the hand. This is a completely natural therapy that affords relief without the
use of drugs. The Reflexology Association of America
(RAA) formally discourages the use of oils or other
preparations in performing this hands-on therapy.

Preparations
In order to realize maximum benefit from a reflexology session, the therapist as well as the patient
should be situated so as to afford optimal comfort
for both. Patients in general receive treatment in a
reclining position, with the therapist positioned as
necessary—to work on the bare feet, or alternately
on the bare hands.
A reflexology patient removes both shoes and
socks in order to receive treatment. No other preparation is involved. No prescription drugs, creams, oils,
or lotions are used on the skin.

Precautions
Reflexology is extremely safe. It may even be selfadministered in a limited form whenever desired. The
qualified reflexologist offers a clear and open disclaimer that reflexology does not constitute medical treatment in any form, nor is reflexology given as a
substitute for medical advice or treatment. The ultimate purpose of the therapy is to promote wellness;
fundamentally it is a form of preventive therapy.
GALE ENCYCLOPEDIA OF MEDICINE

Reflexology

Brain
Ear
Glands

Sinuses

Eye

Nose
Throat

Shoulder
Lungs
Diaphragm

Lungs

Thalmus

Shoulder

Heart
Spleen

Liver
Gallbladder

Adrenal glands
Stomach

Spine
Kidneys

Colon

Bladder

Pancreas

Small
intestine

Colon

Appendix
Pelvis/buttock

Pelvis
Sciatic nerve

Reflexology employs the principle that the reflex points on the feet, when hand pressure is applied, will reflexively stimulate
energy to a related muscle or organ in the body and promote healing. (Illustration by Electronic Illustrators Group.)

People with serious and long-term medical problems are urged to seek the advice of a physician.
Diabetes patients in particular are urged to approach
this therapy cautiously. Likewise pregnant women are
cautioned emphatically to avoid reflexology during
the early phases of pregnancy altogether, as accidentally induced labor and subsequent premature delivery
can result from reflexology treatment.
A consultation with a reflexologist is recommended in order to determine the safety and appropriateness of reflexology therapy for a specific health
problem or condition.

Side effects
Because reflexology is intended to normalize the
body functions, the therapy does not cause a condition
to worsen. Most patients find that pain diminishes
GALE ENCYCLOPEDIA OF MEDICINE

over the course of the therapy. It has been noted,
however, that some patients experience greater discomfort in the second session than in the first session,
because a significant easing of pain and tension is
generally associated with the initial therapy session.
As a result, when pressure is reapplied to the tender
points of the foot during the second session, the sensitivity has been heightened. This increase in sensitivity
may cause minor additional discomfort for the
patient.

Research and general acceptance
Although only one controlled trial of reflexology
therapy, done in 1993, has been documented in medical journals, this therapy is practiced worldwide at
different levels of medical care. In Russia, for example,
only licensed physicians may legally perform
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Reflexology

reflexology treatment. In contrast, the practice is a
commonplace homestyle remedy in the Netherlands.
The Internet ‘‘Home of Reflexology’’ lists at least 66
professional organizations worldwide, including New
Zealand and Malaysia. Associations include the
following:


Academy of Reflexology Austria



Association of Finnish Reflexologists



Chinese Society of Reflexologists



Hellenic Association of Reflexologists



Indian Society for Promotion of Reflexology



International Council of Reflexologists (HQ: San
Diego, USA)



Israeli Reflexology Association



New Zealand Reflexology Association



Polish Instytut of Reflexology (Polish Language)



Reflexology Association of America



Reflexology Association of Australia



Rwo-Shr Health Institute International (Malaysia)



The South African Reflexology Society
Regulatory status

Ongoing legislative debate ensued during the
1990s regarding the legal status of the reflexology
trade. The reflexology community, along with legislators and other bodywork practitioners, engaged in
reassessment of the reflexology business and its relationship to massage therapy and massage parlors.
Organizations and individuals brought judicial
appeals of certain court cases that threatened the legitimate licensing of reflexologists as practitioners of
alternative medicine. Such professional reflexology
interests as the RAA documented in detail the disparities between reflexology and massage, citing the purpose of reflexology, which is to stimulate internal body
functions (glands and organs) as opposed to the topical muscular and joint relief associated with massage.
In a status update in 1998 the Association reported
that 19 states had laws requiring the licensing of massage/reflexology therapists. Licensing laws established
educational requirements and required candidates to
pass written, oral, and/or practical examinations.
Also at issue was a trend among municipalities to
license massage parlors (and reflexologists) under the
business codes affecting the adult entertainment business. B. and K. Kunz reported that judicial decisions
in two states—Tennessee and New Mexico—had
excluded the practice of reflexology practice from the
laws pertaining to massage parlors. Those courts held
3174

KEY TERMS
Pressure points—Specific locations on the feet and
hands that correspond to nerve endings that connect to the organs and glands of the human body
via the spinal cord.
Zone therapy—Also called zone analgesia, a
method of relieving pain by applying pressure to
specific points on the body. It was developed in the
early twentieth century by Dr. William Fitzgerald.

that reflexology is a business separate and distinct
from massage parlors, and deserving of its own respective licensing standards. In Sacramento, California,
reflexologists petitioned successfully to become
licensed as practitioners of somatic therapy rather
than as providers of adult entertainment. Likewise,
in the Canadian province of Ontario, a nonprofit
organization to register reflexology practitioners was
established in order to define a distinct classification
for therapists separate from erotic body rubbers,
which was the original classification given to reflexologists. Other states where court proceedings or legislative attempts to legitimize reflexology have stalled
include Pennsylvania, Florida, New Jersey, and New
York

Training and certification
Training programs
Reflexology is taught by means of a series of
seminars, classes, and training films. Certification is
earned after a six month program that includes 200
hours of training. The certification training breaks
down as follows: 28 hours of preliminary seminar
training; 14 hours of advanced seminar training; 58
hours of self-directed study; and 100 hours of practical
experience, including administering reflexology to a
minimum of 15 people.
Specific aspects of the training include instruction
in the assessment of the pressure points on the feet and
hands through a study of human anatomy. Students
also learn to give reflexology sessions to patients along
with specific techniques for working with the hands.
Certification and advanced certification
As part if its function, the independently organized American Reflexology Certification Board
(ARCB) certifies the competency of reflexology
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Minimum qualifications to take the certification
examination include attendance at an advanced seminar within two years prior to taking the examination.
In addition, the applicant must have attended preliminary seminars for two full days—in addition to the
required day of advanced seminar training—and the
applicant is required to have a minimum of six months
of practical experience in administering the therapy.
Applicants are examined by means of both written
tests and practical demonstrations.
Continuing education certification is available.
Advanced training focuses on mastering the ability
to perform hand reflexology. The therapist also
receives instruction in new and advanced techniques
of basic reflexology. Some reflexology training classes
may be applied toward degree programs in other disciplines, depending on the specific course of study and
the certification of the respective training institutions
involved.
The RAA provides published standards of practice for reflexologists.
Resources
ORGANIZATIONS

International Institute of Reflexology. P.O. Box 12642. St.
Petersburg, FL 33733-2642. (727) 343-4811. Fax: (727)
381-2807. E-mail: fteflex@concentric.net.
Reflexology Association of America. 4012 Rainbow St.
KPMB#585. Las Vegas, NV 89103-2059.

Gloria Cooksey

Refsum’s syndrome see Lipidoses
Regional anesthetic see Anesthesia, local
Regional enteritis see Crohn’s disease

Purpose
The purpose of rehabilitation is to restore some or
all of the patient’s physical, sensory, and mental capabilities that were lost due to injury, illness, or disease.
Rehabilitation includes assisting the patient to compensate for deficits that cannot be reversed medically.
It is prescribed after many types of injury, illness, or
disease, including amputations, arthritis, cancer, cardiac disease, neurological problems, orthopedic injuries, spinal cord injuries, stroke, and traumatic brain
injuries.The Institute of Medicine has estimated that
as many as 14% of all Americans may be disabled at
any given time.

Precautions
Rehabilitation should be carried out only by qualified therapists. Exercises and other physical interventions must take into account the patient’s deficit. An
example of a deficit is the loss of a limb.

Description
A proper and adequate rehabilitation program
can reverse many disabling conditions or can help
patients cope with deficits that cannot be reversed by
medical care. Rehabilitation addresses the patient’s
physical, psychological, and environmental needs. It
is achieved by restoring the patient’s physical functions and/or modifying the patient’s physical and
social environment. The main types of rehabilitation
are physical, occupational, and speech therapy.
Each rehabilitation program is tailored to the
individual patient’s needs and can include one or
more types of therapy. The patient’s physician usually
coordinates the efforts of the rehabilitation team,
which can include physical, occupational, speech, or
other therapists; nurses; engineers; physiatrists (physical medicine); psychologists; orthotists (makes devices
such as braces to straighten out curved or poorly
shaped bones); prosthetists (a therapist who makes
artificial limbs or protheses); and vocational counselors. Family members are often actively involved in the
patient’s rehabilitation program.
Physical therapy

Rehabilitation
Definition
Rehabilitation is a treatment or treatments
designed to facilitate the process of recovery from
injury, illness, or disease to as normal a condition as
possible.
GALE ENCYCLOPEDIA OF MEDICINE

Physical therapy helps the patient restore the use
of muscles, bones, and the nervous system through the
use of heat, cold, massage, whirlpool baths, ultrasound, exercise, and other techniques. It seeks to
relieve pain, improve strength and mobility, and train
the patient to perform important everyday tasks.
Physical therapy may be prescribed to rehabilitate a
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Rehabilitation

practitioners on an individual basis. The ARCB does
not evaluate schools and teachers. Prerequisites for
individual certification include completion of educational requirements and passing a standard qualifying
examiniation. Successful candidates receive the title of
Board Certified Reflexologist.

Rehabilitation
A patient (holding paddles) is undergoing a hydrotherapy treatment. (Photograph by Will & Deni McIntyre, Photo Researchers, Inc.
Reproduced by permission.)

patient after amputations, arthritis, burns, cancer, cardiac disease, cervical and lumbar dysfunction, neurological problems, orthopedic injuries, pulmonary
disease, spinal cord injuries, stroke, traumatic brain
injuries, and other injuries/illnesses. The duration of
the physical therapy program varies depending on the
injury/illness being treated and the patient’s response
to therapy.

and help strengthen movements. Massage aids circulation, helps the patient relax, relieves pain and muscle
spasms, and reduces swelling. Very low strength electrical currents applied through the skin stimulate muscles and make them contract, helping paralyzed or
weakened muscles respond again.

Exercise is the most widely used and best known
type of physical therapy. Depending on the patient’s
condition, exercises may be performed by the patient
alone or with the therapist’s help, or with the therapist
moving the patient’s limbs. Exercise equipment for
physical therapy could include an exercise table or
mat, a stationary bicycle, walking aids, a wheelchair,
practice stairs, parallel bars, and pulleys and weights.

Occupational therapy helps the patient regain the
ability to do normal everyday tasks. This may be
achieved by restoring old skills or teaching the patient
new skills to adjust to disabilities through adaptive
equipment, orthotics, and modification of the
patient’s home environment. Occupational therapy
may be prescribed to rehabilitate a patient after amputation, arthritis, cancer, cardiac disease, head injuries,
neurological injuries, orthopedic injuries, pulmonary
disease, spinal cord disease, stroke, and other injuries/
illnesses. The duration of the occupational therapy
program varies depending on the injury/illness being
treated and the patient’s response to therapy.

Heat treatment, applied with hot-water compresses, infrared lamps, short-wave radiation, high
frequency electrical current, ultrasound, paraffin
wax, or warm baths, is used to stimulate the patient’s
circulation, relax muscles, and relieve pain. Cold treatment is applied with ice packs or cold-water soaking.
Soaking in a whirlpool can ease muscle spasm pain
3176

Occupational therapy

Occupational therapy includes learning how to
use devices to assist in walking (artificial limbs,
GALE ENCYCLOPEDIA OF MEDICINE

Orthotist—A health care professional who is
skilled in making and fitting orthopedic appliances.
Physiatrist—A physician who specializes in physical medicine.
Prosthetist—A health care professional who is
skilled in making and fitting artificial parts (prosthetics) for the human body.

dietary advice to help the patient recover from or
avoid specific problems or diseases.
Rehabiltation centers
Rehabilitation services are provided in a variety of
settings including clinical and office practices, hospitals, skilled-care nursing homes, sports medicine
clinics, and some health maintenance organizations.
Some therapists make home visits. Advice on choosing
the appropriate type of therapy and therapist is provided by the patient’s medical team.
Resources

canes, crutches, walkers), getting around without
walking (wheelchairs or motorized scooters), or moving from one spot to another (boards, lifts, and bars).
The therapist will visit the patient’s home and analyze
what the patient can and cannot do. Suggestions on
modifications to the home, such as rearranging furniture or adding a wheelchair ramp, will be made.
Health aids to bathing and grooming could also be
recommended.
Speech therapy
Speech therapy helps the patient correct speech
disorders or restore speech. Speech therapy may be
prescribed to rehabilitate a patient after a brain injury,
cancer, neuromuscular diseases, stroke, and other
injuries/illnesses. The duration of the speech therapy
program varies depending on the injury/illness being
treated and the patient’s response to therapy.
Performed by a speech pathologist, speech therapy involves regular meetings with the therapist in an
individual or group setting and home exercises. To
strengthen muscles, the patient might be asked to say
words, smile, close his mouth, or stick out his tongue.
Picture cards may be used to help the patient remember everyday objects and increase his vocabulary. The
patient might use picture boards of everyday activities
or objects to communicate with others. Workbooks
might be used to help the patient recall the names of
objects and practice reading, writing, and listening.
Computer programs are available to help sharpen
speech, reading, recall, and listening skills.
Other types of therapists
Inhalation therapists, audiologists, and registered
dietitians are other types of therapists. Inhalation
therapists help the patient learn to use respirators
and other breathing aids to restore or support breathing. Audiologists help diagnose the patient’s hearing
loss and recommend solutions. Dietitians provide
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

National Rehabilitation Association. 633 S. Washington St.,
Alexandria, VA 22314. (703) 836-0850.
National Rehabilitation Information Center. 8455
Colesville Road, Suite 935, Silver Spring, MD 20910.
(800) 34-NARIC.
Rehabilitation International. 25 East 21st St., New York,
NY 10010. (212) 420-1500.

Lori De Milto

Rehydration see Intravenous rehydration

Reiki
Definition
Reiki is a form of therapy that uses simple handson, no-touch, and visualization techniques, with the
goal of improving the flow of life energy in a person.
Reiki (pronounced ray-key) means ‘‘universal life
energy’’ in Japanese, and Reiki practitioners are
trained to detect and alleviate problems of energy
flow on the physical, emotional, and spiritual level.
Reiki touch therapy is used in much the same way to
achieve similar effects that traditional massage therapy
is used—to relieve stress and pain, and to improve the
symptoms of various health conditions.

Purpose
Reiki claims to provide many of the same benefits
as traditional massage therapy, such as reducing
stress, stimulating the immune system, increasing
energy, and relieving the pain and symptoms of health
conditions. Practitioners have reported success in
helping patients with acute and chronic illnesses,
from asthma and arthritis to trauma and recovery
from surgery. Reiki is a gentle and safe technique,
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Reiki

KEY TERMS

Reiki

M I K A O U S U I (1865–1926)
Mikao Usui, born in the Gifu Prefecture (Japan), was
an ethereal child who sought to unravel the mysteries of
the universe. As an adult he developed an interest in the
metaphysical healing talent of Buddha. Usui became
determined to regenerate the healing secrets of Buddha
in order to improve the lot of humanity. He traveled to
many temples and spoke with holy people, but all said
that the secret of Buddha’s powers were lost to the world
due to lack of use.
Eventually the abbot of a Zen monastery encouraged
Usui to study the ancient writings containing the secrets
on healing. Usui learned two new languages, Chinese
and Sanskrit, in order to understand the writings better,
and from his reading he obtained the formula for healing.
The Sutras in particular provided the enlightenment that
he sought.
Usui next set out to obtain the power to heal. It is
widely believed that he developed that ability after
spending 21 days in retreat and in fasting on the holy
Mountain of Kori-yama, where he had a vision of light
and received the knowledge of the symbols of reiki and
their use in healing. He officially formulated Usui Reiki
therapy in 1922 and touted as many as one million
followers during his lifetime.
Prior to the transition (death) of Usui, he imparted
the secrets of healing to 16 teachers in order that the
secrets would not be lost again.

and has been used successfully in some hospitals. It
has been found to be very calming and reassuring for
those suffering from severe or fatal conditions. Reiki
can been used by doctors, nurses, psychologists and
other health professionals to bring touch and deeper
caring into their healing practices.

Description
Origins
Reiki was developed in the mid-1800s by Dr.
Mikao Usui, a Japanese scholar of religion.
According to the story that has been passed down
among reiki teachers, Usui was a Christian who was
intrigued by the idea that Christ could heal sick people
by touching them with his hands. Searching for clues
that would explain the secrets of healing with hands,
Usui made a long pilgrimage around the world, visiting many ancient religious sects and studying ancient
books. Some reiki teachers claim that Usui found clues
3178

leading back nearly 10,000 years to healing arts that
originated in ancient Tibet. During his intense studies,
Usui claimed he had a spiritual experience, which
enabled him to heal with his own hands by becoming
aware of and tapping into the universal life force.
After that, he dedicated his life to helping the sick
and poor. His reputation grew as he healed sick people
for many years in Kyoto, Japan. Before his death,
Usui passed on his healing insights using universal
life energy to Dr. Chujiru Hayashi, a close acquaintance. Hayashi, in turn, passed on the healing techniques in 1938 to Hawayo Takata, a Japanese woman
from Hawaii, whom he had cured of life-threatening
illness using reiki methods. Takata became a firm
believer and proponent of reiki, and during the 1970s
formed an initiation program for training reiki masters to preserve Usui’s teachings. Before she died, she
prepared her granddaughter, Phyllis Lei Furumoto, to
continue the lineage. Takata had personally trained 21
practitioners before she died at the age of 80 in 1980.
Along with other reiki masters authorized by Takata,
Furumoto formed the reiki Alliance. A faction led by
Barbara Ray, formed the American Reiki
Association, which was known as Radiance
Technique Association International. Today, there
are over 1,000 reiki masters practicing around the
world, whose methods can all be traced back directly
to Dr. Usui.
The basic philosophy of reiki
The basic concept underlying reiki is that the body
has an energy field that is central to its health and
proper functioning, and this energy travels in certain
pathways that can become blocked or weakened. This
idea of energy flow in the body is also a central concept
in Ayurvedic medicine and traditional Chinese medicine, including acupuncture.
Reiki practitioners believe that everyone has the
potential to access the universal life energy, but that
over time most people’s systems become blocked and
the energy becomes weakened in them. A reiki practitioner is trained to be able to detect these blockages,
and practitioners will use their hands, thoughts, and
own energy fields to improve the energy flow in a
patient. Reiki is one of the more esoteric alternative
medical practices, because no one is sure exactly how it
works on the physiological level. Practitioners claim
that it works on very subtle energy levels, or possibly
works on the chakra system. The chakras are the
system of seven energy centers along the middle of
the body believed to be connected with the nervous
and endocrine systems, as defined by yoga and
Ayurvedic medicine. Reiki masters claim that healing
GALE ENCYCLOPEDIA OF MEDICINE

According to the original principles of Usui,
patients must also have a proper attitude for reiki to
work most effectively. Patients must take responsibility for their own health, and must want to be healed.
Furthermore, when energy is received from a reiki
healer, patients must be willing to give back energy
to others, and to compensate the healer in some way,
as well. Finally, Usui claimed that a healing attitude
was free from worry and fear, was filled with gratitude
for life and for others, and placed emphasis on each
person finding honest and meaningful work in their
lives—all this, in order to complete the picture of overall health.
A reiki session
Reiki sessions can take various forms, but most
commonly resemble typical bodywork appointments,
where the receiver lies clothed on his or her back on a
flat surface or massage table. A session generally lasts
from an hour to an hour and a half. Reiki is a simple
procedure, consisting of calm and concentrated touching, with the practitioner focusing on healing and giving energy to specific areas on the receiver’s body.
Practitioners place their hands over positions on the
body where the organs and endocrine glands reside,
and the areas that correspond to the chakra centers.
Practitioners also use mental visualization to send
healing energy to areas of the receiver’s body that
need it. In special cases or with injuries, a no-touch
technique is used, where the practitioner’s hands are
sometimes held just above the body without touching
it. Advanced practitioners rely on intuition and experience to determine which areas of a body need the most
energy healing.
The practitioner’s hands are held flat against the
receiver’s body, with the fingertips touching. There
can be over 20 positions on both sides of the body
where the hands are placed. The positions begin at the
crown of the head and move towards the feet. The
receiver usually turns over once during the session.
The practitioner’s hands are held in each position for
a usually five minutes, to allow the transfer of energy
and the healing process to take place. In each position,
the hands are kept stationary, unlike typical massage
where the hands move, and both the giver and receiver
attempt to maintain an attitude of awareness, openness, and caring.
GALE ENCYCLOPEDIA OF MEDICINE

Reiki practitioners recommend that those receiving reiki for the first time go through a series of three
to four initial treatments over the course of about a
week, to allow for cleansing and the initial readjustment of energy. Reiki sessions can cost from $30–100
per session. Insurance coverage is rare, and consumers
should consult their individual policies as to whether
or not such therapies are included.
Self-treatment with reiki
Although reiki practitioners believe that formal
training is necessary to learn the proper methods of
energy channeling and healing, individuals can still use
some of the basic positions of reiki to relieve stress and
to stimulate healing on themselves or another. The
positions can be performed anywhere and for however
long they are needed. Positions generally move from
the top of the body down, but positions can be used
wherever there is pain or stress. Mental attitude is
important during reiki; the mind should be cleared of
all stressful thoughts and concentrated on compassion, love, and peace as forms of energy that are
surrounding, entering, and healing the body.
The following positions are illustrated in Reiki:
Energy Medicine:


Position one: Hands are placed on the top of the
head, with the wrists near the ears and the fingertips
touching on the crown of the head. Eyes should be
closed. Hold for five minutes or more, until the mind
feels clear and calm.



Position two: Cup the hands slightly and place the
palms over the closed eyes, with the fingers resting on
the forehead.



Position three: Place the hands on the sides of the
head, with the thumbs behind the ear and the palms
over the lower jaws, with the fingers covering the
temples.



Position four: Place one hand on the back of the
neck, at the base of the skull, and put the other
hand on the head just above it, parallel to it.



Position five: Wrap the hands around the front of the
throat, and rest them there gently with the heels of
the hands touching in front.



Position six: Place each hand on top of a shoulder,
close to the side of neck, on top of the trapezius
muscle.



Position seven: Form a T-shape with the hands over
the chest, with the left hand covering the heart and
the right hand above it, covering the upper part of the
chest.
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Reiki

energy can even be sent to a person from far away,
noting that reiki works on the same principles that
enables praying to work for some patients, although
a practitioner needs advanced training to be able to
send energy from afar.

Reiki

KEY TERMS
Attunement—Life energy teaching given by Reiki
master to a student.
Chakra—One of seven major energy centers in the
body, as defined by Hindu and yoga philosophy.
Relaxation response—The human body’s response
to relaxation techniques, during which metabolism
and stress levels decrease and immune response
increases.



Position eight: The hands are placed flat against the
front of the body with fingertips touching. Hold for
five minutes or so, and repeat four or five times,
moving down a hand-width each time until the pelvic
region is reached, which is covered with a v-shape of
the hands. Then, for the final position, repeat this
technique on the back, beginning as close to the
shoulders as the hands can reach, and ending by
forming a T-shape with the hands at the base of the
spine.

Side effects
Reiki generally has no side effects, as it is a very
low impact and gentle procedure. Some receivers
report tingling or sensations of heat or cold during
treatment. Others have reported sadness or anxiety
during treatment, which practitioners claim are buried
or repressed emotions being released by the new
energy flow.

Research and general acceptance
Reiki has been used in major clinics and hospitals
as part of alternative healing practice, and doctors,
dentists, nurses and other health professionals have
been trained to use its gentle touch techniques as part
of their practice. To date, the little scientific research
that has been conducted with reiki implies that its
techniques bring about the relaxation response, in
which stress levels decrease, and immune response
increases. Reiki practitioners claim that the most
important measurement of their technique is whether
the individual feels better after treatment. They also
claim that science cannot measure the subtle energy
changes that they are attempting to bring about.
As of the early 2000s, there are differences of
opinion within the mainstream medical community
regarding the acceptability of reiki. On the one hand,
3180

medical professionals in Canada have proposed strategies to limit the popularity of reiki as well as several
other alternative therapies by resisting the integration
of these therapies with mainstream treatments and by
opposing government research in complementary and
alternative medicine. On the other hand, the U. S.
National Center for Complementary and Alternative
Medicine (NCCAM) is conducting a series of clinical
trials to evaluate the efficacy of reiki. As of the summer of 2004, there are four NCCAM trials for reiki,
measuring its effectiveness in treating such disorders
as fibromyalgia, neuropathy, prostate cancer, and
advanced AIDS.

Training and certification
Reiki practitioners undergo a series of attunements, which are sessions with reiki masters that
teach the basic methods of energy healing. Several
organizations provide resources for reiki training.
Reiki practitioners believe these attunements are
necessary for correct technique. The masters teach
each person how to activate the universal life energy
in themselves before they can pass it on to others.
These initiations often are held during weekend workshops. Trainees can achieve up to four levels of attunements, until they reach the level of master
themselves. The certification process is not a formal
one; masters approve students when they feel satisfied
with their progress.
Resources
PERIODICALS

Hallett, A. ‘‘Narratives of Therapeutic Touch.’’ Nursing
Standard 19 (September 15, 2004): 33–37.
Kelner, M., B. Wellman, H. Boon, and S. Welch.
‘‘Responses of Established Healthcare to the
Professionalization of Complementary and Alternative
Medicine in Ontario.’’ Social Science and Medicine 59
(September 2004): 915–930.
ORGANIZATIONS

International Association of Reiki Professionals. P.O. Box
481, Winchester, MA 01890. <http://www.iarp.org>.
International Center for Reiki Training. 21421 Hilltop
Street, Unit #28, Southfield, MI 48034. (800) 332-8112
or (248) 948-8112. Fax: (248) 948-9534. <http://
www.reiki.org>.
National Center for Complementary and Alternative
Medicine (NCCAM) Clearinghouse. P. O. Box 7923.
Gaitherburg, MD 20898. (888) 644-6226. Fax: (866)
464-3616.<http://nccam.nih.gov>.
OTHER

American Reiki Masters Association (ARMA). PO Box 130,
Lake City, FL 32056-0130. (904) 755-9638.
GALE ENCYCLOPEDIA OF MEDICINE

Reiter’s syndrome

Global Reiki Healing Network. <http://www.reiki.org>.
NCCAM Reiki Clinical Trials. <http://nccam.nih.gov/
clinicaltrials/reiki.htm>.
Reiki Alliance. P.O. Box 41, Cataldo, ID 83810-1041, phone
(208) 682-3535.

Douglas Dupler, MA
Rebecca J. Frey, PhD

Reiter’s syndrome
Definition
Reiter’s syndrome (RS), which is also known as
arthritis urethritica, venereal arthritis, reactive arthritis, and polyarteritis enterica, is a form of arthritis that
affects the eyes, urethra, and skin, as well as the joints.
It was first described by Hans Reiter, a German physician, during World War I.

Keratoderma, a skin condition characterized by horny
patches, is one symptom of Reiter’s syndrome. (Photograph
by Milton Reisch, M.D., Corbis Images. Reproduced by
permission.)



inflammation of the urethra, with painful urination
and a discharge from the penis



mouth ulcers



inflammation of the eye



keratoderma blennorrhagica, these are patches of
scaly skin on the palms, soles, trunk, or scalp of RS
patients

Description
Reiter’s syndrome is marked by a cluster of symptoms in different organ systems of the body that may
or may not appear simultaneously. The disease may be
acute or chronic, with spontaneous remissions or
recurrences.
RS primarily affects sexually active males between
ages 20–40, particularly males who are HIV positive.
Most women and children who develop RS acquire the
disease in its intestinal form.

Causes and symptoms
The cause of Reiter’s syndrome was unknown as
of early 1998, but scientists think the disease results
from a combination of genetic vulnerability and various disease agents. Over 80% of Caucasian patients
and 50–60% of African Americans test positive for
HLA-B27, which suggests that the disease has a
genetic component. In sexually active males, most
cases of RS follow infection with Chlamydia trachomatis or Ureaplasma urealyticum. Other patients
develop the symptoms following gastrointestinal
infection with Shigella, Salmonella, Yersinia, or
Campylobacter bacteria.
The initial symptoms of RS are inflammation
either of the urethra or the intestines, followed by
acute arthritis four to 28 days later. The arthritis
usually affects the fingers, toes, and weight-bearing
joints in the legs. Other symptoms include:
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Patient history
Diagnosis of Reiter’s syndrome can be complicated by the fact that different symptoms often occur
several weeks apart. The patient does not usually
draw a connection between the arthritis and previous
sexual activity. The doctor is likely to consider
Reiter’s syndrome when the patient’s arthritis occurs
together with or shortly following inflammation of
the eye and the genitourinary tract lasting a month or
longer.
Laboratory tests
There is no specific test for diagnosing RS, but
the physician may have the urethral discharge cultured to rule out gonorrhea. Blood tests of RS
patients are typically positive for the HLA-B27
genetic marker, with an elevated white blood cell
(WBC) count and an increased sedimentation rate
of red blood cells. The patient may also be mildly
anemic.
3181

Relapsing fever

KEY TERMS
Acute—Having a sudden onset and lasting a short
time.
Chronic—Of long duration.
Keratoderma blennorrhagica—The medical name
for the patches of scaly skin that occur on the arms,
legs, and trunk of RS patients.
Reactive arthritis—Another name for Reiter’s
syndrome.

Hellman, David B. ‘‘Arthritis & Musculoskeletal
Disorders.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Relapsing fever
Definition

Diagnostic imaging
X rays do not usually reveal any abnormalities
unless the patient has had recurrent episodes of the
disease. Joints that have been repeatedly inflamed may
show eroded areas, signs of osteoporosis, or bony spurs
when x rayed.

Treatment
There is no specific treatment for RS. Joint
inflammation is usually treated with nonsteroidal
anti-inflammatory drugs (NSAIDs.) Skin eruptions
and eye inflammation can be treated with corticosteroids. Gold treatments may be given for eroded bone.
Patients with chronic arthritis are also given physical therapy and advised to exercise regularly.

Prognosis
The prognosis varies. Most patients recover in
three to four months, but about 50% have recurrences
for several years. Some patients develop complications
that include inflammation of the heart muscle, stiffening inflammation of the vertebrae, glaucoma, eventual
blindness, deformities of the feet, or accumulation of
fluid in the lungs.

Prevention
In males, Reiter’s syndrome can be prevented by
sexual abstinence or the use of condoms.
Resources

Relapsing fever refers to two similar illnesses, both
of which cause high fevers. The fevers resolve, only to
recur again within about a week.

Description
Relapsing fever is caused by spiral-shaped bacteria of the genus Borrelia. This bacterium lives in
rodents and in insects, specifically ticks and body
lice. The form of relapsing fever acquired from ticks
is slightly different from that acquired from body lice.
In tick-borne relapsing fever (TBRF), rodents
(rats, mice, chipmunks, and squirrels) which carry
Borrelia are fed upon by ticks. The ticks then acquire
the bacteria, and are able to pass it on to humans.
TBRF is most common in sub-Saharan Africa, parts
of the Mediterranean, areas in the Middle East, India,
China, and the south of Russia. Also, Borrelia causing
TBRF exist in the western regions of the United
States, particularly in mountainous areas. The disease
is said to be endemic to these areas, meaning that the
causative agents occur naturally and consistently
within these locations.
In louse-borne relapsing fever (LBRF), lice
acquire Borrelia from humans who are already
infected. These lice can then go on to infect other
humans. LBRF is said to be epidemic, as opposed to
endemic, meaning that it can occur suddenly in large
numbers in specific communities of people. LBRF
occurs in places where poverty and overcrowding predispose to human infestation with lice. LBRF has
flared during wars, when conditions are crowded and
good hygiene is next to impossible. At this time, LBRF
is found in areas of east and central Africa, China, and
in the Andes Mountains of Peru.

BOOKS

Berktow, Robert, editor. ‘‘Musculoskeletal and Connective
Tissue Disorders: Reiter’s Syndrome (RS).’’ In The
Merck Manual of Diagnosis and Therapy. 16th ed.
Rahway, NJ: Merck Research Laboratories, 1992.
3182

Causes and symptoms
In TBRF, humans contract Borrelia when they are
fed upon by ticks. Ticks often feed on humans at night,
GALE ENCYCLOPEDIA OF MEDICINE

In LBRF, a louse must be crushed or smashed in
order for Borrelia to be released. The bacteria then
enter the human body through areas where the person
may have scratched him or herself.
Both types of relapsing fever occur some days
after having acquired the bacteria. About a week
after becoming infected, symptoms begin. The patient
spikes a very high fever, with chills, sweating, terrible
headache, nausea, vomiting, severe pain in the muscles
and joints, and extreme weakness. The patient may
become dizzy and confused. The eyes may be bloodshot and very sensitive to light. A cough may develop.
The heart rate is greatly increased, and the liver and
spleen may be swollen. Because the substances responsible for blood clotting may be disturbed during the
illness, tiny purple marks may appear on the skin,
which are evidence of minor bleeding occurring
under the skin. The patient may suffer from a nosebleed, or may cough up bloody sputum. All of these
symptoms last for about three days in TBRF, and
about five days in LBRF.
With or without treatment, a crisis may occur as
the bacteria are cleared from the blood. This crisis,
called a Jarisch-Herxheimer reaction, results in a new
spike in fever, chills, and an initial rise in blood pressure. The blood pressure then falls drastically, which
may deprive tissues and organs of appropriate blood
flow (shock). This reaction usually lasts for about a day.
Recurrent episodes of fever with less severe symptoms occur after about a week. In untreated infections,
fevers recur about three times in TBRF, and only once
or twice in LBRF.

Diagnosis
Diagnosis of relapsing fever is relatively easy,
because the causative bacteria can be found by examining a sample of blood under the microscope. The
characteristically spiral-shaped bacteria are easily
identifiable. The blood is best drawn during the period
of high fever, because the bacteria are present in the
blood in great numbers at that time.

Treatment
Either tetracycline or erythromycin is effective
against both forms of relapsing fever. The medications
are given for about a week for cases of TBRF; LBRF
requires only a single dose. Children and pregnant
women should receive either erythromycin or penicillin.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Endemic—Refers to a particular organism which
consistently exists in a particular location under
normal conditions.
Epidemic—Refers to a condition suddenly
acquired by a large number of people within a
specific community, and which spreads rapidly
throughout that community.
Shock—A state in which the blood pressure is so
low that organs and tissues are not receiving an
appropriate flow of blood.

Because of the risk of the Jarish-Herxheimer reaction,
patients must be very carefully monitored during the
initial administration of antibiotic medications.
Solutions containing salts must be given through a
needle in the vein (intravenously) to keep the blood
pressure from dropping too drastically. Patients with
extreme reactions may need medications to improve
blood circulation until the reaction resolves.

Prognosis
In epidemics of LBRF, death rates among
untreated victims have run as high as 30%. With
treatment, and careful monitoring for the development of the Jarish-Herxheimer reaction, prognosis is
good for both LBRF and TBRF.

Prevention
Prevention of TBRF requires rodent control,
especially in and near homes. Careful use of insecticides on skin and clothing is important for people who
may be enjoying outdoor recreation in areas known to
harbor the disease-carrying ticks.
Prevention of LBRF is possible, but probably
more difficult. Good hygiene and decent living conditions would prevent the spread of LBRF, but these
may be difficult for those people most at risk for the
disease.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD
3183

Relapsing fever

so many people who have been bitten are unaware that
they have been. The bacteria is passed on to humans
through the infected body fluids of the tick.

Relapsing polychondritis

KEY TERMS

Relapsing polychondritis
Definition
Relapsing polychondritis is a disease characterized by autoimmune-like episodic or progressive
inflammation of cartilage and other connective tissue,
such as the nose, ears, throat, joints, kidneys, and
heart.

Description
Cartilage is a tough, flexible tissue that turns into
bone in many places in the body. Bones all start out as
cartilage in the fetus. Consequently, children have
more cartilage than adults. Cartilage persists in adults
in the linings of joints, the ears, the nose, the airway
and the ribs near the breast bone. All these sites are
attacked by relapsing polychondritis, which usually
occurs equally in middle-aged males and females. It
is frequently diagnosed along with rheumatoid arthritis, systemic lupus erythematosus, and other connective
tissue diseases.

Causes and symptoms
The most common first symptom of relapsing
polychondritis is pain and swelling of the external
ear. Usually, both ears turn red or purple and are
tender to the touch. The swelling can extend into
the ear canal and beyond, causing ear infections,
hearing loss, balance disturbances with vertigo
and vomiting, and eventually a droopy ear. The nose
is often afflicted as well and can deteriorate into a
flattened nose bridge called saddle nose.
Inflammation of the eye occurs less frequently, but
can lead to blindness.
As relapsing polychondritis advances, it causes
more dangerous symptoms such as deterioration of
the cartilage that holds the windpipe open.
Progressive disease can destroy the integrity of the
airway and compromise breathing. Destruction of
the rib cartilage can collapse the chest, again hindering breathing. Joints everywhere are involved in episodes of arthritis, with pain and swelling. Other
tissues besides cartilage are also involved, leading
to a variety of problems with the skin and other
tissues. Occasionally, the aorta or heart valves are
damaged.
The disease may occur in episodes with complete
remission between, or it may smolder along for years,
causing progressive destruction.
3184

Aorta—The biggest artery in the body, receiving
blood directly from the heart.
Connective tissue—Several types of tissue that
hold the body’s parts together–tendons, ligaments,
fascia, and cartilage.
Inflammation—The body’s immune reaction to
presumed foreign substances like germs.
Inflammation is characterized by increased blood
supply and activation of defense mechanisms. It
produces redness, swelling, heat, and pain.

Diagnosis
A characteristic array of symptoms and physical
findings will yield a diagnosis of relapsing polychondritis. Laboratory tests are sometime helpful.
Biopsies of the affected cartilage may confirm the
diagnosis. Further diagnostic tests are done to confirm other associated conditions such as rheumatoid
arthritis. It is important to evaluate the airway,
although only 10% of patients will die from airway
complications.

Treatment
Mild inflammations can be treated with aspirin
or nonsteroidal anti-inflammatory drugs (NSAIDs)
such as ibuprofen. Corticosteroids (most often prednisone) are usually prescribed for more advanced
conditions and do improve the disease. They may
have to be continued over long periods of time, in
which case their usage must be closely watched to
avoid complications. Immune suppression with
cyclophosphamide, azathioprine, cyclosporine, or
dapsone is reserved for more aggressive cases. A
collapsed chest or airway may require surgical support, and a heart valve or aorta may need repair or
replacing.

Prognosis
There is no known cure for relapsing polychondritis. It can only be combated with each onset of
inflammation and deterioration of cartilaginous tissue. As the disease progresses over a period of
years, the mortality rate increases. At five years
duration, relapsing polychondritis has a 30% mortality rate.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

BOOKS

Gilliland, Bruce C. ‘‘Relapsing Polychondritis and Other
Arthritides.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Renal artery occlusion
Definition
Renal artery occlusion is a blockage of the major
arteries that supply blood to the kidneys caused by
thrombosis or embolism.

Angioplasty—A non-surgical procedure that uses a
balloon-tipped catheter to open a blocked artery.
Artherosclerotic plaque—A deposit of fatty and
calcium substances that accumulate in the lining
of the artery wall, restricting blood flow.
Atrophy—Cell or tissue wasting or death.
Chronic kidney failure—End-stage renal disease
(ESRD); chronic kidney failure is diagnosed as
ESRD when kidney function falls to 5–10% of
capacity.
Embolism—Blood vessel obstruction by a blood
clot or other substance (i.e., air).
Thrombus—Formation of a blood clot within the
vascular system. A thrombus becomes an embolism if it breaks away and blocks a blood vessel.

Description
Renal artery occlusion occurs when the flow of
blood from the arteries leading to the kidneys becomes
blocked by a blood clot or cholesterol emboli. The lack
of oxygenation can lead to necrosis (tissue death) and
ultimately, chronic kidney failure.

Causes and symptoms
Renal arterial occlusion occurs when a thrombus
or embolism (blood clot or cholesterol plaque) breaks
free and blocks the arteries leading to one or both
kidneys.
Symptoms of an acute renal arterial occlusion
may include:


hypertension



fever



sudden pain in the lower back or flank



nausea and vomiting



protein and/or blood in the urine

An individual with renal arterial occlusion may
have no overt symptoms, particularly if only one kidney is affected or if the blockage is only partial. Health
problems from secondary complications such as
chronic kidney failure may be the first indication that
something is wrong.

Diagnosis
The high blood pressure that is sometimes associated with a renal artery blockage may be the first sign
GALE ENCYCLOPEDIA OF MEDICINE

that it is present, particularly if the hypertension is not
responding to standard treatment. Urine and blood tests
may or may not be useful in diagnosing this condition.
Blood tests may show an elevated plasma creatinine
level. If kidney tissue infarction (cell death caused by a
lack of blood supply) has occurred, lactic dehydrogenase
(LDH) may also be present in the urine and blood.
An arteriogram, an x-ray study of the arteries that
uses a radiopaque substance, or dye, to make the
arteries visible under x ray, may also be performed.
This test is used with caution in patients with impaired
kidney function, as the contrast medium can cause
further kidney damage. In patients with whom this is
not an issue, a spiral computed tomography (CT) scan
with contrast medium may also be used.

Treatment
Occlusions may be treated with anticoagulant
(blood thinning) or thrombolytic (clot destroying)
drugs. If the blockage is significant, surgical intervention
or angioplasty may be required. Between 1996 and 2000,
the number of these procedures performed on Medicare
patients more than doubled, said a 2004 report.

Alternative treatment
Renal arterial occlusion is a serious and potentially life-threatening condition, and should always be
treated by a healthcare professional familiar with the
disorder.
3185

Renal artery occlusion

Resources

Renal artery stenosis

Prognosis

Description

The outcome of renal arterial occlusion depends
on the speed with which it is treated. Once the blood
supply is minimized or cut off to the kidney, tissue
death soon results, ultimately leading to chronic kidney failure (end-stage renal disease).

Prevention
Atherosclerosis may encourage the formation of
cholesterol emboli, a potential cause of renal artery
occlusion. Strategies for avoiding vascular disease
include eating right, maintaining a desirable weight,
quitting smoking, managing stress, and exercising regularly. People prone to emboli from blood clots can take
blood thinning drugs to prevent potential emboli from
loding in the renal artery.
Resources
PERIODICALS

Bloch, M. J., and T. Pickering. ‘‘Renal Vascular Disease:
Medical Management, Angioplasty, and Stenting.’’
Seminars in Nephrology 20, no. 5 (September 2000):
474-88.
‘‘Explosive Growth Seen in Renal Artery Interventional
Procedures.’’ Heart Disease Weekly September 26,
2004: 20.
Truelove, Christiane. ‘‘First for Pulmonary Embolism.’’
Med Ad News August 2004: 82.
ORGANIZATIONS

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://www.arbon.com/kidney/>.
National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK). Natcher Building, 6AS-13K, 45
Center Drive, Bethesda, MD 20892-6600. <http://
www.niddk.nih.gov>.
National Kidney Foundation. 30 East 33rd Street, New
York, NY 10016. (800)622-9020. <http://
www.kidney.org>.

Paula Anne Ford-Martin
Teresa G. Odle

Renal artery stenosis
Definition
Renal artery stenosis is a blockage or narrowing
of the major arteries that supply blood to the kidneys.
3186

Renal artery stenosis occurs when the flow of
blood from the arteries leading to the kidneys is constricted by tissue or artherosclerotic plaque. This narrowing of the arteries diminishes the blood supply to
the kidneys, which can cause them to atrophy and may
ultimately lead to kidney failure. It may also cause
renovascular hypertension, or high blood pressure
related to renal artery blockage.

Causes and symptoms
The two main causes of renal artery stenosis are
atherosclerosis
and
fibromuscular
disease.
Fibromuscular diseases such as fibromuscular dysplasia cause growth of fibrous tissues on the arterial wall.
Stenosis may also occur when scar tissue forms in the
renal artery after trauma to the kidney.
Renal arterial stenosis has no overt symptoms.
Eventually, untreated renal arterial stenosis causes
secondary complications such as chronic kidney failure, which may be characterized by frequent urination,
anemia, edema, headaches, hypertension, lower back
pain, and other signs and symptoms.

Diagnosis
The high blood pressure that is sometimes associated with renal artery stenosis may be the first sign
that it is present, particularly if the hypertension is not
responding to standard treatment. Presence of a bruit,
a swooshing sound from the artery that indicates an
obstruction, may be heard through a stethoscope.
An arteriogram, an x-ray study of the arteries that
uses a radiopaque substance, or dye, to make the
arteries visible under x ray, may also be performed.
This test is used with caution in patients with impaired
kidney function, as the contrast medium may cause
further kidney damage.

Treatment
Treatment for renal artery stenosis is either surgical, pharmaceutical, or with angioplasty or stenting.
Angioplasty involves guiding a balloon catheter down
into the renal artery and inflating the balloon to clear
the blockage. A stent may be inserted into the artery to
widen the opening. Some patients may be candidates
for surgical revascularization, which involves restoring blood flow with an arterial bypass. Drugs known
as angiotension-converting enzyme (ACE) inhibitors
may be prescribed for some patients. The chosen treatment approach depends on the cause of the stenosis
GALE ENCYCLOPEDIA OF MEDICINE

Artherosclerotic plaque—A deposit of fatty and
calcium substances that accumulate in the lining
of the artery wall, restricting blood flow.
Atrophy—Cell or tissue wasting or death.
Chronic kidney failure—End-stage renal disease
(ESRD); chronic kidney failure is diagnosed as
ESRD when kidney function falls to 5–10% of
capacity.
Edema—Swelling which occurs when body tissues
retain fluid.
Stent—An expandable ‘‘scaffold-like’’ device,
usually constructed of a stainless steel material,
that is inserted into an artery to expand the inside
passage and improve blood flow.

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800)638-8299.
<http://www.arbon.com/kidney/>.
National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK). Natcher Building, 6AS-13K, 45
Center Drive, Bethesda, MD 20892-6600. <http://
www.niddk.nih.gov>.
National Kidney Foundation. 30 East 33rd Street, New
York, NY 10016. (800)622-9020. <http://
www.kidney.org>.

Paula Anne Ford-Martin

Renal calculi see Kidney stones
Renal failure see Acute kidney failure;
Chronic kidney failure
Renal nuclear medicine scan see Kidney
nuclear medicine scan

and factors such as the patient’s kidney function and
blood pressure control.

Alternative treatment
Renal artery stenosis is a serious and potentially
life-threatening condition, and should always be treated by a healthcare professional familiar with the
disorder.

Prognosis
Untreated renal artery stenosis can cause hypertension (high blood pressure) and may ultimately lead
to chronic kidney failure (end-stage renal disease).

Prevention
Maintaining a heart healthy lifestyle can help to
prevent cases of renal arterial stenosis attributable to
artherosclerosis. Strategies for avoiding vascular disease include eating right, maintaining a desirable
weight, quitting smoking, managing stress, and exercising regularly.
Resources
PERIODICALS

Bloch, M. J., and T. Pickering. ‘‘Renal Vascular Disease:
Medical Management, Angioplasty, and Stenting.’’
Seminars in Nephrology 20, no. 5 (September 2000): 474-88.
Fenves, A. Z., and C. V. Ram. ‘‘Fibromuscular Dysplasia of
the Renal Arteries.’’ Current Hypertension Reports 1,
no. 6 (December 1999): 546-9.
GALE ENCYCLOPEDIA OF MEDICINE

Renal tubular acidosis
Definition
Renal tubular acidosis (RTA) is a condition characterized by too much acid in the body due to a defect
in kidney function.

Description
Chemical balance is critical to the body’s functioning. Therefore, the body controls its chemicals
very strictly. The acid-base balance must be between
a pH of 7.35 and 7.45 or trouble will start. Every other
chemical in the body is affected by the acid-base balance. The most important chemicals in this system are
sodium, chloride, potassium, calcium, ammonium,
carbon dioxide, oxygen, and phosphates.
The lungs rapidly adjust acid-base balance by the
speed of breathing, because carbon dioxide dissolved in
water is an acid–carbonic acid. Faster breathing eliminates more carbon dioxide, decreases the carbonic acid
in the blood and increases the pH. Holding your breath
does the opposite. Blood acidity from carbon dioxide
controls the rate of breathing, not oxygen.
The kidneys also regulate acid-base balance somewhat more slowly than the lungs. They handle all the
chemicals, often trading one for another that is more
or less acidic. The trading takes place between the
blood and the urine, so that extra chemicals end up
passing out of the body. If the kidneys do not
3187

Renal tubular acidosis

ORGANIZATIONS

KEY TERMS

Renal vein thrombosis

effectively eliminate acid, it builds up in the blood,
leading to a condition called metabolic acidosis.
These conditions are called renal tubular acidosis.

Causes and symptoms
There are three types of renal tubular acidosis.
They include:


Distal renal tubular acidosis (type 1) may be a hereditary condition or may be triggered by an autoimmune
disease,
lithium
therapy,
kidney
transplantation, or chronic obstruction.



Proximal renal tubular acidosis (type 2) is caused by
hereditary diseases, such as Fanconi’s syndrome, fructose intolerance, and Lowe’s syndrome. It can also
develop with vitamin D deficiency, kidney transplantation, heavy metal poisoning, and treatment with
certain drugs.



Type 4 renal tubular acidosis is not hereditary, but is
associated with diabetes mellitus, sickle cell anemia, an
autoimmune disease, or an obstructed urinary tract.

Symptoms vary with the underlying mechanism of
the defect and the readjustment of chemicals required
to compensate for the defect.






Distal RTA results in high blood acidity and low
blood potassium levels. Symptoms include mild
dehydration; muscle weakness or paralysis (due to
potassium deficiency); kidney stones (due to excess
calcium in the urine); and bone fragility and pain.
Proximal RTA also results in high blood acidity and
low blood potassium levels. Symptoms include mild
dehydration.
Type 4 RTA is characterized by high blood acidity
and high blood potassium levels; it rarely causes
symptoms unless potassium levels rise so high as to
cause heart arrhythmias or muscle paralysis.

KEY TERMS
Autoimmune disease—Type of diseases characterized by antibodies that attack the body’s own
tissues.
Fanconi’s syndrome—A disorder of the kidneys
characterized by glucose in the urine.
Lowe’s syndrome—A rare inherited disorder that is
distinguished by congenital cataracts, glaucoma,
and severe mental retardation.
Rickets—A deficiency disease that affects the bone
development of growing bodies, usually causing
soft bones.

potassium is reduced. This is done by changing the
diet and by using diuretic medicines that promote
potassium excretion in the urine.

Prognosis
Careful balancing of body chemicals will usually
produce good results. If there is an underlying disease
responsible for the kidney malfunction, it may be the
determining factor in the prognosis.

Prevention
Relatives of patients with the possibly hereditary
forms of renal tubular acidosis should be tested.
Resources
BOOKS

Chesney, Russell W. ‘‘Specific Renal Tubular Disorders.’’ In
Cecil Textbook of Medicine, edited by J. Claude Bennett
and Fred Plum. Philadelphia: W. B. Saunders Co., 1996.

J. Ricker Polsdorfer, MD

Diagnosis
RTA is suspected when a person has certain symptoms indicative of the disease or when routine tests
show high blood acid levels and low blood potassium
levels. From there, more testing of blood and urine
chemicals will help determine the type of RTA present.

Treatment
The foundation of treatment for RTA types 1 and
2 is replacement of alkali (base) by drinking a bicarbonate solution daily. Potassium may also have to be
replaced, and other chemicals added to maintain balance. In type 4 RTA acidity will normalize if
3188

Renal ultrasound see Abdominal ultrasound

Renal vein thrombosis
Definition
Renal vein thrombosis develops when a blood clot
forms in the renal vein, which carries blood from the
kidneys back to the heart. The disorder is not
common.
GALE ENCYCLOPEDIA OF MEDICINE

Renal vein thrombosis occurs in both infants and
adults. Onset of the disorder can be rapid (acute) or
gradual. The number of people who suffer from renal
vein thrombosis is difficult to determine, as many
people do not show symptoms, and the disorder is
diagnosed only by specific tests. Ninety percent of
childhood cases occur in children under one year old,
and 75% occur in infants under one month of age. In
adult women, oral contraceptive use increases the risk
of renal vein thrombosis.

Prognosis
Most cases of renal vein thrombosis resolve without any permanent damage. Death from renal vein
thrombosis is rare, and is often caused by the blood
clot detaching and lodging in the heart or lungs.

Prevention
There is no specific prevention for renal vein
thrombosis. Preventing dehydration reduces the risk
that it will occur.
Resources

Causes and symptoms
In children, renal vein thrombosis almost always
occurs rapidly after an episode of severe dehydration.
Severe dehydration decreases blood volume and
causes the blood to clot more readily.
In adults, renal vein thrombosis can be caused by
injury to the abdomen or back, as a result of malignant
kidney tumors growing into the renal vein, or as a
result of kidney diseases that cause degenerative
changes in the cells of the renal tubules (nephrotic
syndrome).
Acute onset of renal vein thrombosis at any age
causes pain in the lower back and side, fever, bloody
urine, decreased urine output, and sometimes kidney
failure. In adults, when the onset of the disorder is
gradual, there is a slow decrease in kidney function,
and protein appears in the urine. Many adults with
renal vein thrombosis show few symptoms.

Diagnosis
Renal venography, where a contrast material (dye)
is injected into the renal vein before x rays are taken,
is one of the best ways to detect renal vein thrombosis.
Other useful tests to detect a clot include computed
tomography scans (CT scans), magnetic resonance
imaging (MRI), and ultrasound.

Treatment
One of the major goals of treatment is to prevent
the blood clot in the renal vein from detaching and
moving into the lungs, where it can cause serious
complications as a pulmonary embolism. The enzyme
streptokinase may be given to help dissolve the renal
clot. Anticoagulant medications are usually prescribed
to prevent clots from recurring. Rarely, when there is a
complete blockage of the renal vein in infants, the
kidney must be surgically removed.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010.<http://www.kidney.org>.
OTHER

‘‘Renal Vein Thrombosis.’’ HealthAnswers.com. <http://
www.healthanswers.com/database/ami/converted/
ooo513.html>.

Tish Davidson, A.M.

Rendu-Osler-Weber disease see Hereditary
hemorrhagic telangiectasia
Renin assay see Plasma renin activity

Renovascular hypertension
Definition
Renovascular hypertension is a secondary form of
high blood pressure caused by a narrowing of the renal
artery.

Description
Primary hypertension, or high blood pressure,
affects millions of Americans. It accounts for over
90% of all cases of hypertension and develops without
apparent causes. It is helpful for the clinician to know
if a secondary disease is present and may be contributing to the high pressure. If clinical tests indicate this is
so, the term used for the rise in blood pressure is
secondary hypertension.
Renal hypertension is the most common form of
secondary hypertension and affects no more than one
percent of all adults with primary hypertension. There
are two forms of renovascular hypertension.
3189

Renovascular hypertension

Description

Renovascular hypertension

In atherosclerotic renovascular hypertension disease, plaque is deposited in the renal artery. The deposits
narrow the artery, disrupting blood flow.
Atherosclerotic renovascular hypertension is most
often seen in men over age 45 and accounts for twothirds of the cases of renovascular hypertension. In most
patients, it affects the renal arteries to both kidneys.
Renovascular hypertension caused by fibromuscular dysplasia occurs mainly in women under age 45.
It is also the cause of hypertension in 10% of children
with the disorder. In fibromuscular dysplasia, cells
from the artery wall overgrow and cause a narrowing
of the artery channel.
The risk of having hypertension is related to age,
lifestyle, environment, and genetics. Smoking, stress,
obesity, a diet high in salt, exposure to heavy metals,
and an inherited predisposition toward hypertension
all increase the chances that a person will develop both
primary and renovascular hypertension.

Causes and symptoms
Narrowing of the renal artery reduces the flow of
blood to the kidney. In response, the kidney produces
the protein renin. Renin is released into the blood
stream. Through a series of steps, renin is converted
into an enzyme that causes sodium (salt) retention and
constriction of the arterioles. In addition to atherosclerotic and fibromuscular dysplasia, narrowing of
the renal artery can be caused by compression from
an injury or tumor, or by blood clots.
Renovascular hypertension is suspected when
hypertension develops suddenly in patients under 30
or over 55 years of age or abruptly worsens in any
patient. Symptoms are often absent or subtle.

Diagnosis
No single test for renovascular hypertension is
definitive. About half of patients with renovascular
hypertension have a specific cardiovascular sound that
is heard when a doctor listens to the upper abdomen
with a stethoscope. Other diagnostic tests give occasional false positive and false negative results. Most
tests are expensive, and some involve serious risks.
Imaging studies are used to diagnose renovascular
hypertension. In intravenous urography, a dye is injected
into the kidney, pictures are made, and the kidneys compared. In renal arteriography, contrast material is
inserted into the renal artery and cinematic x rays (showing motion within the kidney) are taken. Studies of kidney
function are performed. Tests are done to measure renin
3190

production. The results of these tests taken together are
used to diagnose renovascular hypertension.

Treatment
Renovascular hypertension may not respond well
to anti-hypertensive drugs. Percutaneous transluminal
angioplasty (PTA), where a balloon catheter is used to
dilate the renal artery and remove the blockage, is
effective in improving the condition of about 90% of
patients with fibromuscular dysplasia. One year later,
60% remain cured. It is less successful in patients with
atherosclerosis, where renovascular hypertension
recurs in half the patients. Where kidney damage
occurs, surgery to repair or bypass the renal artery
blockage is often effective. In some cases, the damaged
kidney must be removed.

Alternative treatment
Alternative treatment stresses eliminating the root
causes of hypertension. With renovascular hypertension, as with primary hypertension, the root causes
generally cannot be totally reversed by any method.
Lifestyle changes are recommended. These include
stopping smoking, eating a diet low in animal fats
and salt, avoiding exposure to heavy metals, stress
control through meditation, and anger management.
Herbal medicine practitioners recommend garlic
(Allium sativum ) to help lower blood pressure.
Constitutional homeopathy and acupuncture also can
be helpful in lowering blood pressure.

Prognosis
PTA is effective in many younger patients with
fibromuscular dysplasia. Older patients are less
responsive to this treatment. Surgery is also more
risky and less successful in older patients.

Prevention
Renovascular hypertension is possibly preventable through lifestyles that prevent atherosclerosis and
primary hypertension. It is unknown how to prevent
fibromuscular hyperplasia
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Tish Davidson, A.M.
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Respiratory acidosis is a condition in which a
build-up of carbon dioxide in the blood produces a
shift in the body’s pH balance and causes the body’s
system to become more acidic. This condition is
brought about by a problem either involving the
lungs and respiratory system or signals from the
brain that control breathing.

pH—A measurement of acid or alkali (base) of a
solution based on the amount of hydrogen ions
available. Based on a scale of 14, a pH of 7.0 is
neutral. A pH below 7.0 is an acid; the lower the
number, the stronger the acid. A pH above 7.0 is a
base; the higher the number, the stronger the base.
Blood pH is slightly alkali with a normal range of
7.36–7.44.

Description
Respiratory acidosis is an acid imbalance in the
body caused by a problem related to breathing. In
the lungs, oxygen from inhaled air is exchanged for
carbon dioxide from the blood. This process takes
place between the alveoli (tiny air pockets in the
lungs) and the blood vessels that connect to them.
When this exchange of oxygen for carbon dioxide is
impaired, the excess carbon dioxide forms an acid in
the blood. The condition can be acute with a sudden
onset, or it can develop gradually as lung function
deteriorates.

Causes and symptoms
Respiratory acidosis can be caused by diseases or
conditions that affect the lungs themselves, such as
emphysema, chronic bronchitis, asthma, or severe pneumonia. Blockage of the airway due to swelling, a foreign object, or vomit can induce respiratory acidosis.
Drugs like anesthetics, sedatives, and narcotics can
interfere with breathing by depressing the respiratory
center in the brain. Head injuries or brain tumors can
also interfere with signals sent by the brain to the
lungs. Such neuromuscular diseases as Guillain-Barré
syndrome or myasthenia gravis can impair the muscles
around the lungs making it more difficult to breathe.
Conditions that cause chronic metabolic alkalosis can
also trigger respiratory acidosis.
The most notable symptom will be slowed or
difficult breathing. Headache, drowsiness, restlessness, tremor, and confusion may also occur. A rapid
heart rate, changes in blood pressure, and swelling of
blood vessels in the eyes may be noted upon examination. This condition can trigger the body to
respond with symptoms of metabolic alkalosis,
which may include cyanosis, a bluish or purplish discoloration of the skin due to inadequate oxygen
intake. Severe cases of respiratory acidosis can lead
to coma and death.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Respiratory acidosis may be suspected based on
symptoms. A blood sample to test for pH and arterial
blood gases can be used to confirm the diagnosis. In
this type of acidosis, the pH will be below 7.35. The
pressure of carbon dioxide in the blood will be high,
usually over 45 mmHg.

Treatment
Treatment focuses on correcting the underlying
condition that caused the acidosis. In patients with
chronic lung diseases, this may include use of a
bronchodilator or steroid drugs. Supplemental oxygen supplied through a mask or small tubes inserted
into the nostrils may be used in some conditions,
however, an oversupply of oxygen in patients with
lung disease can make the acidosis worse. Antibiotics
may be used to treat infections. If the acidosis is
related to an overdose of narcotics, or a drug overdose is suspected, the patient may be given a dose of
naloxone, a drug that will block the respiratorydepressing effects of narcotics. Use of mechanical
ventilation like a respirator may be necessary. If
the respiratory acidosis has triggered the body to
compensate by developing metabolic alkalosis,
symptoms of that condition may need to be treated
as well.

Prognosis
If the underlying condition that caused the
respiratory acidosis is treated and corrected, there
may be no long term effects. Respiratory acidosis
may occur chronically along with the development of
lung disease or respiratory failure. In these severe conditions, the patient may require the assistance of a
respirator or ventilator. In extreme cases, the patient
may experience coma and death.
3191

Respiratory acidosis

KEY TERMS

Respiratory acidosis

Respiratory alkalosis

Prevention
Patients with chronic lung diseases and those who
receive sedatives and narcotics need to be monitored
closely for development of respiratory acidosis.
Resources
BOOKS

‘‘Fluid, Electrolyte, and Acid-Base Disorders.’’ In Family
Medicine Principles and Practices. 5th ed. New York:
Springer-Verlag, 1998.

Altha Roberts Edgren

KEY TERMS
Hyperventilation—Rapid, deep breathing, possibly exceeding 40 breaths/minute. The most common cause is anxiety, although fever, aspirin
overdose, serious infections, stroke, or other diseases of the brain or nervous system.
pH—A measurement of acid or alkali (base) of a
solution based on the amount of hydrogen ions
available. Based on a scale of 14, a pH of 7.0 is
neutral. A pH below 7.0 is an acid; the lower the
number, the stronger the acid. A pH above 7.0 is a
base; the higher the number, the stronger the base.
Blood pH is slightly alkali with a normal range of
7.36-7.44.

Respiratory alkalosis
Definition
Respiratory alkalosis is a condition where the
amount of carbon dioxide found in the blood drops
to a level below normal range. This condition produces a shift in the body’s pH balance and causes the
body’s system to become more alkaline (basic). This
condition is brought on by rapid, deep breathing
called hyperventilation.

Description
Respiratory alkalosis is an alkali imbalance in the
body caused by a lower-than-normal level of carbon
dioxide in the blood. In the lungs, oxygen from inhaled
air is exchanged for carbon dioxide from the blood.
This process takes place between the alveoli (tiny air
pockets in the lungs) and the blood vessels that connect to them. When a person hyperventilates, this
exchange of oxygen for carbon dioxide is speeded up,
and the person exhales too much carbon dioxide. This
lowered level of carbon dioxide causes the pH of the
blood to increase, leading to alkalosis.

Causes and symptoms
The primary cause of respiratory alkalosis is
hyperventilation. This rapid, deep breathing can be
caused by conditions related to the lungs like pneumonia, lung disease, or asthma. More commonly, hyperventilation is associated with anxiety, fever, drug
overdose, carbon monoxide poisoning, or serious infections. Tumors or swelling in the brain or nervous
system can also cause this type of respiration. Other
stresses to the body, including pregnancy, liver failure,
3192

high elevations, or metabolic acidosis can also trigger
hyperventilation leading to respiratory alkalosis.
Hyperventilation, the primary cause of respiratory alkalosis, is also the primary symptom. This
symptom is accompanied by dizziness, light headedness, agitation, and tingling or numbing around the
mouth and in the fingers and hands. Muscle twitching,
spasms, and weakness may be noted. Seizures, irregular heart beats, and tetany (muscle spasms so severe
that the muscle locks in a rigid position) can result
from severe respiratory alkalosis.

Diagnosis
Respiratory alkalosis may be suspected based on
symptoms. A blood sample to test for pH and arterial
blood gases can be used to confirm the diagnosis. In
this type of alkalosis, the pH will be elevated above
7.44. The pressure of carbon dioxide in the blood will
be low, usually under 35 mmHg.

Treatment
Treatment focuses on correcting the underlying
condition that caused the alkalosis. Hyperventilation
due to anxiety may be relieved by having the patient
breath into a paper bag. By rebreathing the air that
was exhaled, the patient will inhale a higher amount of
carbon dioxide than he or she would normally.
Antibiotics may be used to treat pneumonia or other
infections. Other medications may be required to treat
fever, seizures, or irregular heart beats. If the alkalosis
is related to a drug overdose, the patient may require
treatment for poisoning. Use of mechanical ventilation
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
If the underlying condition that caused the
respiratory alkalosis is treated and corrected, there
may be no long-term effects. In severe cases of respiratory alkalosis, the patient may experience seizures or
heart beat irregularities that may be serious and life
threatening.

and, by the time the fetal lungs mature at 37 weeks, a
normal amount is present.
If an infant is born prematurely, enough surfactant might not have formed in the alveoli causing the
lungs to collapse and making it very difficult for the
baby to get enough air (and the oxygen it contains).
Sometimes a layer of fibrous tissue called a hyaline
membrane forms in the air sacs, making it even harder
for oxygen to get through to the blood vessels. RDS in
newborn infants used to be called hyaline membrane
disease.

Causes and symptoms
Resources
BOOKS

‘‘Fluid, Electrolyte, and Acid-Base Disorders.’’ In Family
Medicine Principles and Practices. 5th ed. New York:
Springer-Verlag, 1998.

Altha Roberts Edgren

Respiratory distress syndrome
Definition
Respiratory distress syndrome (RDS) of the newborn, also known as infant RDS, is an acute lung
disease present at birth, which usually affects premature babies. Layers of tissue called hyaline membranes
keep the oxygen that is breathed in from passing into
the blood. The lungs are said to be ‘‘airless.’’ Without
treatment, the infant will die within a few days after
birth, but if oxygen can be provided, and the infant
receives modern treatment in a neonatal intensive care
unit, complete recovery with no after-effects can be
expected.

Description
If a newborn infant is to breathe properly, the
small air sacs (alveoli) at the ends of the breathing
tubes must remain open so that oxygen in the air can
get into the tiny blood vessels that surround the
alveoli. Normally, in the last months of pregnancy,
cells in the alveoli produce a substance called surfactant, which keep the surface tension inside the alveoli
low so that the sacs can expand at the moment of birth,
and the infant can breathe normally. Surfactant is
produced starting at about 34 weeks of pregnancy
GALE ENCYCLOPEDIA OF MEDICINE

RDS nearly always occurs in premature infants,
and the more premature the birth, the greater is the
chance that RDS will develop. RDS also is seen in
some infants whose mothers are diabetic.
Paradoxically, RDS is less likely in the presence of
certain states or conditions which themselves are
harmful: abnormally slow growth of the fetus; high
blood pressure, a condition called preeclampsia in the
mother; and early rupture of the birth membranes.
Labored breathing (the ‘‘respiratory distress’’ of
RDS) may begin as soon as the infant is born, or
within a few hours. Breathing becomes very rapid,
the nostrils flare, and the infant grunts with each
breath. The ribs, which are very flexible in young
infants, move inwards each time a breath is taken.
Before long the muscles that move the ribs and diaphragm, so that air is drawn into the lungs, become
fatigued. When the oxygen level in the blood drops
severely the infant’s skin turns bluish in color. Tiny,
very premature infants may not even have signs of
trouble breathing. Their lungs may be so stiff that
they cannot even start breathing when born.
There are two major complications of RDS. One
is called pneumothorax, which means ‘‘air in the
chest.’’ When the infant itself or a breathing machine
applies pressure on the lungs in an attempt to expand
them, a lung may rupture, causing air to leak into the
chest cavity. This air causes the lung to collapse
further, making breathing even harder and interfering
with blood flow in the lung arteries. The blood pressure can drop suddenly, cutting the blood supply to
the brain. The other complication is called intraventricular hemorrhage; this is bleeding into the cavities
(ventricles) of the brain, which may be fatal.

Diagnosis
When a premature infant has obvious trouble
breathing when born or within a few hours of birth,
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Respiratory distress syndrome

like a respirator may be necessary. If the respiratory
alkalosis has triggered the body to compensate by
developing metabolic acidosis, symptoms of that condition may need to be treated, as well.

Respiratory distress syndrome

RDS is an obvious possibility. If premature birth is
expected, or there is some condition that calls for
delivery as soon as possible, the amount of surfactant
in the amniotic fluid will indicate how well the lungs
have matured. If little surfactant is found in an amniotic fluid sample taken by placing a needle in the uterus
(amniocentesis), there is a definite risk of RDS. Often
this test is done at regular intervals so that the infant
can be delivered as soon as the lungs are mature. If the
membranes have ruptured, surfactant can easily be
measured in a sample of vaginal fluid.
The other major diagnostic test is a chest x ray.
Collapsed lung tissue has a typical appearance, and the
more lung tissue is collapsed, the more severe the RDS.
An x ray also can demonstrate pneumothorax (air or
gas in the area around the lung), if this complication has
occurred. The level of oxygen in the blood can be
measured by taking a blood sample from an artery,
or, more easily, using a device called an oximeter,
which is clipped to an earlobe. Pneumothorax may
have occurred if the infant suddenly becomes worse
while on ventilation; x rays can help make the diagnosis.

Treatment
If only a mild degree of RDS is present at birth,
placing the infant in an oxygen hood may be enough. It
is important to guard against too much oxygen, as this
may damage the retina and cause loss of vision. Using
an oximeter to keep track of the blood oxygen level,
repeated artery punctures or heel sticks can be avoided.
In more severe cases a drug very like natural surfactant
(Exosurf Neonatal or Survanta), can be dripped into
the lungs through a fine tube (endotracheal tube) placed
in the infant’s windpipe (trachea). Typically the infant
will be able to breathe more easily within a few days at
the most, and complications such as lung rupture are
less likely to occur. The drug is continued until the
infant starts producing its own surfactant. There is a
risk of bleeding into the lungs from surfactant treatment; about 10% of the smallest infants are affected.
Infants with severe RDS may require treatment
with a ventilator, a machine that takes over the work
of the lungs and delivers air under pressure. In tiny
infants who do not breathe when born, ventilation
through a tracheal tube is an emergency procedure.
Assisted ventilation must be closely supervised, as too
much pressure can cause further lung damage. A gentler
way of assisting breathing, continuous positive airway
pressure or CPAP, delivers an oxygen mixture through
nasal prongs or a tube placed through the nose rather
than an endotracheal tube. CPAP may be tried before
resorting to a ventilator, or after an infant placed on a
3194

ventilator begins to improve. Drugs that stimulate
breathing may speed the recovery process.
Pneumothorax is an emergency that must be treated right away. Air may be removed from the chest
using a needle and syringe. A tube then is inserted into
the lung cavity, and suction applied.

Prognosis
If an infant born with RDS is not promptly treated, lack of an adequate oxygen supply will damage
the body’s organs and eventually cause them to stop
functioning altogether. Death is the result. The central
nervous system in particular–made up of the brain and
spinal cord–is very dependent on a steady oxygen
supply and is one of the first organ systems to feel
the effects of RDS. On the other hand, if the infant’s
breathing is supported until the lungs mature and
make their own surfactant, complete recovery within
three to five days is the rule.
If an air leak causes pneumothorax, immediate
removal of air from the chest will allow the lungs to reexpand. Bleeding into the brain is a very serious condition that worsens the outlook for an infant with RDS.

Prevention
The best way of preventing RDS is to delay delivery until the fetal lungs have matured and are producing enough surfactant–generally at about 37 weeks of
pregnancy. If delivery cannot be delayed, the mother
may be given a steroid hormone, similar to a natural
substance produced in the body, which crosses the
barrier of the placenta and helps the fetal lungs to
produce surfactant. The steroid should be given at
least 24 hours before the expected time of delivery. If
the infant does develop RDS, the risk of bleeding into
the brain will be much less if the mother has been given
a dose of steroid.
If a very premature infant is born without symptoms
of RDS, it may be wise to deliver surfactant to its lungs.
This may prevent RDS, or make it less severe if it does
develop. An alternative is to wait until the first symptoms of RDS appear and then immediately give surfactant. Pneumothorax may be prevented by frequently
checking the blood oxygen content, and limiting oxygen
treatment under pressure to the minimum needed.
Resources
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Alveoli—The small air sacs located at the ends of
the breathing tubes of the lung, where oxygen normally passes from inhaled air to blood vessels.
Amniotic fluid—The fluid bathing the fetus, which
may be sampled using a needle to determine
whether the fetus is making enough surfactant.
Endotracheal tube—A metal or plastic tube
inserted in the windpipe which may be attached
to a ventilator. It also may be used to deliver medications such as surfactant.
Hyaline membranes—A fibrous layer that settles in
the alveoli in RDS, and prevents oxygen from
escaping from inhaled air to the bloodstream.
Pneumothorax—Air in the chest, often a result of
the lung rupturing when oxygen is delivered under
too high a pressure.
Preeclampsia—A disease of pregnancy in which
the mother’s blood pressure is elevated; associated
with both maternal and fetal complications, and
sometimes with fetal death.
Steroid—A natural body substance that often is
given to women before delivering a very premature
infant to stimulate the fetal lungs to produce surfactant, hopefully preventing RDS (or making it less
severe).
Surfactant—A material normally produced in the
fetal lungs in the last months of pregnancy, which
helps the air sacs to open up at the time of birth so
that the newborn infant can breathe freely.
Ventilator—A machine that can breathe for an
infant having RDS until its lungs are producing
enough surfactant and are able to function normally.

National Respiratory Distress Syndrome Foundation. P.O.
Box 723, Montgomeryville, PA 18936.

David A. Cramer, MD

Respiratory failure
Definition
Respiratory failure is nearly any condition that
affects breathing function or the lungs themselves
GALE ENCYCLOPEDIA OF MEDICINE

and can result in failure of the lungs to function properly. The main tasks of the lungs and chest are to get
oxygen from the air that is inhaled into the bloodstream, and, at the same to time, to eliminate carbon
dioxide (C02) from the blood through air that is
breathed out. In respiratory failure, the level of oxygen
in the blood becomes dangerously low, and/or the
level of C02 becomes dangerously high. There are
two ways in which this can happen. Either the process
by which oxygen and C02 are exchanged between the
blood and the air spaces of the lungs (a process called
‘‘gas exchange’’) breaks down, or the movement of air
in and out of the lungs (ventilation) does not take place
properly.

Description
Respiratory failure often is divided into two main
types. One of them, called hypoxemic respiratory failure, occurs when something interferes with normal gas
exchange. Too little oxygen gets into the blood
(hypoxemia), and all organs and tissues in the body
suffer as a result. One common type of hypoxemic
failure, occurring in both adults and prematurely
born infants, is respiratory distress syndrome, a condition in which fluid or tissue changes prevent oxygen
from passing out of the air sacs of the lungs into the
circulating blood. Hypoxemia also may result from
spending time at high altitudes (where there is less
oxygen in the air); various forms of lung disease that
separate oxygen from blood in the lungs; severe anemia (‘‘low blood’’); and blood vessel disorders that
shunt blood away from the lungs, thus precluding
the lungs from picking up oxygen.
The other main type of respiratory failure is ventilatory failure, occurring when, for any reason,
breathing is not strong enough to rid the body of
C02. Then CO2 builds up in the blood (hypercapnia).
Ventilatory failure can result when the respiratory
center in the brainstem fails to drive breathing; when
muscle disease keeps the chest wall from expanding
when breathing in; or when a patient has chronic
obstructive lung disease that makes it very difficult to
exhale air with its C02. Many of the specific diseases
and conditions that cause respiratory failure cause
both too little oxygen in the blood (hypoxemia) and
abnormal ventilation.

Causes and symptoms
Several different abnormalities of breathing function can cause respiratory failure. The major categories, with specific examples of each, are:
3195

Respiratory failure

KEY TERMS

Respiratory failure



Obstruction of the airways. Examples are chronic
bronchitis with heavy secretions; emphysema; cystic
fibrosis; asthma (a condition in which it is very hard
to get air in and out through narrowed breathing
tubes).



Weak breathing. This can be caused by drugs or
alcohol, which depress the respiratory center;
extreme obesity; or sleep apnea, where patients stop
breathing for long periods while sleeping.



Muscle weakness. This can be caused by a muscle
disease called myasthenia; muscular dystrophy; polio;
a stroke that paralyzes the respiratory muscles; injury
of the spinal cord; or Lou Gehrig’s disease.



Lung diseases, including severe pneumonia.
Pulmonary edema, or fluid in the lungs, can be the
source of respiratory failure. Also, it can often be a
result of heart disease; respiratory distress syndrome;
pulmonary fibrosis and other scarring diseases of the
lung; radiation exposure; burn injury when smoke is
inhaled; and widespread lung cancer.



An abnormal chest wall (a condition that can be
caused by scoliosis or severe injury of the chest wall).

A majority of patients with respiratory failure are
short of breath. Both low oxygen and high carbon
dioxide can impair mental functions. Patients may
become confused and disoriented and find it impossible to carry out their normal activities or do their
work. Marked C02 excess can cause headaches and,
in time, a semi-conscious state, or even coma. Low
blood oxygen causes the skin to take on a bluish
tinge. It also can cause an abnormal heart rhythm
(arrhythmia). Physical examination may show a
patient who is breathing rapidly, is restless, and has a
rapid pulse. Lung disease may cause abnormal sounds
heard when listening to the chest with a stethoscope:
wheezing in asthma, ‘‘crackles’’ in obstructive lung
disease. A patient with ventilatory failure is prone to
gasp for breath, and may use the neck muscles to help
expand the chest.

causes the resistance in these vessels to increase, which
can be measured using a special catheter. A high blood
level of C02 may cause increased pressure in the fluid
surrounding the brain and spinal cord; this, too, can
be measured.

Treatment
Nearly all patients are given oxygen as the first
treatment. Then the underlying cause of respiratory
failure must be treated. For example, antibiotics are
used to fight a lung infection, or, for an asthmatic
patient, a drug to open up the airways is commonly
prescribed.
A patient whose breathing remains very poor will
require a ventilator to aid breathing. A plastic tube is
placed through the nose or mouth into the windpipe
and is attached to a machine that forces air into the
lungs. This can be a lifesaving treatment and should
be continued until the patient’s own lungs can take
over the work of breathing. It is very important to use
no more pressure than is necessary to provide sufficient oxygen; otherwise ventilation may cause further
lung damage. Drugs are given to keep the patient
calm, and the amount of fluid in the body is carefully
adjusted so that the heart and lungs can function as
normally as possible. Steroids, which combat inflammation, may sometimes be helpful but they can cause
complications, including weakening the breathing
muscles.
The respiratory therapist has a number of methods available to help patients overcome respiratory
failure. They include:


Suctioning the lungs through a small plastic tube
passed through the nose, in order to remove secretions from the airways that the patient cannot cough
up.



Postural drainage, in which the patient is propped up
at an angle or tilted to help secretions drain out of the
lungs. The therapist may clap the patient on the chest
or back to loosen the secretions, or a vibrator may be
used for the same purpose.



Breathing exercises often are prescribed after the
patient recovers. They make the patient feel better
and help to strengthen the muscles that aid breathing. One useful method is for the patient to suck on a
tube attached to a clear plastic hosing containing a
ball so as to keep the ball lifted. Regular deep breathing exercises are simpler and often just as helpful.
Another technique is to have the patient breathe out
against pursed lips to increase pressure in the airways
and keep them from collapsing.

Diagnosis
The symptoms and signs of respiratory failure are
not specific. Rather, they depend on what is causing
the failure and on the patient’s condition before it
developed. Good general health and some degree of
‘‘reserve’’ lung function will help see a patient through
an episode of respiratory failure. The key diagnostic
determination is to measure the amount of oxygen,
carbon dioxide, and acid in the blood at regular intervals. A sudden low oxygen level in the lung tissue may
cause the arteries of the lungs to narrow. This, in turn,
3196

GALE ENCYCLOPEDIA OF MEDICINE

Chronic obstructive lung disease—A common
form of lung disease in which breathing, and therefore gas exchange, is labored and increasingly
difficult.
Gas exchange—The process by which oxygen is
extracted from inhaled air into the bloodstream,
and, at the same time, carbon dioxide is eliminated
from the blood and exhaled.
Hypoxemia—An abnormally low amount of oxygen in the blood, the major consequence of respiratory failure, when the lungs no longer are able to
perform their chief function of gas exchange.
Pulmonary fibrosis—An end result of many forms
of lung disease (especially chronic inflammatory
conditions). Normal lung tissue is converted to
scarred, ‘‘fibrotic’’ tissue that cannot carry out gas
exchange.

prevention is to treat any lung disease promptly and
effectively. It is also important to make sure that any
patient who has had lung disease is promptly treated
for any respiratory infection (even of the upper
respiratory tract). Patients with lung problems should
also avoid exposure to pollutants, as much as is possible. Once respiratory failure is present, it is best for a
patient to receive treatment in an intensive care unit,
where specialized personnel and all the needed equipment are available. Close supervision of treatment,
especially mechanical ventilation, will help minimize
complications that would compound the problem.
Resources
ORGANIZATIONS

National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Respiratory Distress Syndrome Foundation. P.O.
Box 723, Montgomeryville, PA 18936.

David A. Cramer, MD

Prognosis
The outlook for patients with respiratory failure
depends chiefly on its cause. If the underlying disease
can be effectively treated, with the patient’s breathing
supported in the meantime, the outlook is usually
good.
Care is needed not to expose the patient to polluting substances in the atmosphere while recovering
from respiratory failure; this could tip the balance
against recovery. When respiratory failure develops
slowly, pressure may build up in the lung’s blood
vessels, a condition called pulmonary hypertension.
This condition may damage the vessels, worsen
hypoxemia, and cause the heart to fail. If it is not
possible to provide enough oxygen to the body, complications involving either the brain or the heart may
prove fatal.
If the kidneys fail or the diseased lungs become
infected, the prognosis is worse. In some cases, the primary disease causing the lungs to fail is irreversible. The
patient, family, and physician together then must decide
whether to prolong life by ventilator support.
Occasionally, lung transplantation is a possibility, but it
is a highly complex procedure and is not widely available

Prevention
Because respiratory failure is not a disease itself,
but the end result of many lung disorders, the best
GALE ENCYCLOPEDIA OF MEDICINE

Respiratory syncytial virus
infection
Definition
Respiratory syncytial virus (RSV) is a virus that
can cause severe lower respiratory infections in children under the age of two, and milder upper respiratory
infections in older children and adults. RSV infection
is also called bronchiolitis, because it is marked in
young children by inflammation of the bronchioles.
Bronchioles are the narrow airways that lead from the
bronchi to the tiny air sacs (alveoli) in the lungs. The
result is wheezing, difficulty breathing, and sometimes
fatal respiratory failure.

Description
RSV infection is caused by a group of viruses
found worldwide. There are two different subtypes of
the virus with numerous different strains. Taken
together, these viruses account for a significant number of deaths in infants.
RSV infection is primarily a disease of winter or
early spring, with waves of illness sweeping through a
community. The rate of RSV infection is estimated to
be 11.4 cases in every 100 children during their first
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Respiratory syncytial virus infection

KEY TERMS

Respiratory syncytial virus infection

year of life. In the United States, RSV infection occurs
most frequently in infants between the ages of two
months and six months.



shortness of breath



labored breathing out (exhalations)

RSV infection shows distinctly different symptoms, depending on the age of the infected person. In
children under two, the virus causes a serious lower
respiratory infection in the lungs. In older children and
healthy adults, it causes a mild upper respiratory infection often mistaken for the common cold.



bluish tinge to the skin (cyanosis)



croupy, seal-like, barking cough



high fever

Although anyone can get this disease, infants suffer the most serious symptoms and complications.
Breast feeding seems to provide partial protection
from the virus. Conditions in infants that increase
their risk of infection include:

Breathing problems occur in RSV infections
because the bronchioles swell, making it difficult for
air to get in and out of the lungs. If the child is having
trouble breathing, immediate medical care is needed.
Breathing problems are most common in infants
under one year of age; they can develop rapidly.



premature birth

Diagnosis



lower socio-economic environment

Physical examination and imaging studies



congenital heart disease



chronic lung diseases, such as cystic fibrosis



immune system deficiencies, including HIV infection



immunosuppressive therapy given to organ transplant patients

Many older children and adults get RSV infection, but the symptoms are so similar to the common
cold that the true cause is undiagnosed. People of any
age with weakened immune systems, either from such
diseases as AIDS or leukemia, or as the result of
chemotherapy or corticosteroid medications, are
more at risk for serious RSV infections. So are people
with chronic lung disease.

Causes and symptoms
Respiratory syncytial virus is spread through
close contact with an infected person. It has been
shown that if a person with RSV infection sneezes,
the virus can be carried to others within a radius of 6
f (1.8 m). This group of viruses is hardy. They can live
on the hands for up to half an hour and on toys or
other inanimate objects for several hours.
Scientists have yet to understand why RSV viruses
attack the lower respiratory system in infants and the
upper respiratory system in adults. In infants, RSV
begins with such cold symptoms as a low fever, runny
nose, and sore throat. Soon, other symptoms appear
that suggest an infection which involves the lower airways. Some of these symptoms resemble those of
asthma. RSV infection is suggested by:


wheezing and high-pitched, whistling breathing



rapid breathing (more than 40 breaths per minute)

3198

RSV infection is usually diagnosed during a physical examination by the pediatrician or primary care
doctor. The doctor listens with a stethoscope for
wheezing and other abnormal lung sounds in the
patient’s chest. The doctor will also take into consideration whether there is a known outbreak of RSV
infection in the area. Chest x rays give some indication
of whether the lungs are hyperinflated from an effort
to move air in and out. X rays may also show the
presence of a secondary bacterial infection, such as
pneumonia.
Laboratory tests
A blood test can also detect RSV infection. This
test measures the level of antibodies the body has
formed against the virus. The blood test is less reliable
in infants than in older children because antibodies in
the infant’s blood may have come from the mother
during pregnancy. If infants are hospitalized, other
tests such as an arterial blood gas analysis are done to
determine if the child is receiving enough oxygen.

Treatment
Home care
Home treatment for RSV infection is primarily
supportive. It involves taking steps to ease the child’s
breathing. Dehydration can be a problem, so children
should be encouraged to drink plenty of fluids.
Antibiotics have no effect on viral illnesses. In time,
the body will make antibodies to fight the infection
and return itself to health.
Home care for keeping a child with RSV comfortable and breathing more easily includes:
GALE ENCYCLOPEDIA OF MEDICINE



Use a cool mist room humidifier to ease congestion
and sore throat.
Raise the baby’s head by putting books under the
head end of the crib.



Give acetaminophen (Tylenol, Pandol, Tempra) for
fever. Aspirin should not be given to children because
of its association with Reye’s syndrome, a serious
disease.



For babies too young to blow their noses, suction
away any mucus with an infant nasal aspirator.
Hospital treatment

In the United States, RSV infections are responsible for 90,000 hospitalizations and 4,500 deaths each
year. Children who are hospitalized receive oxygen
and humidity through a mist tent or vaporizer. They
also are given intravenous fluids to prevent dehydration. Mechanical ventilation may be necessary. Blood
gases are monitored to assure that the child is receiving
enough oxygen.
Medications
Bronchiodilators, such as albuterol (Proventil,
Ventilin), may be used to keep the airways open.
Ribavirin (Virazole) is used for desperately ill children
to stop the growth of the virus. Ribavirin is both
expensive and has toxic side effects, so its use is
restricted to the most severe cases.

Alternative treatment
Alternative medicine has little to say specifically
about bronchiolitis, especially in very young children.
Practitioners emphasize that people get viral illnesses
because their immune systems are weak. Prevention
focuses on strengthening the immune system by eating
a healthy diet low in sugars and high in fresh fruits and
vegetables, reducing stress, and getting regular, moderate exercise. Like traditional practitioners, alternative practitioners recommend breastfeeding infants so
that the child may benefit from the positive state of
health of the mother. Inhaling a steaming mixture of
lemon oil, thyme oil, eucalyptus, and tea tree oil (aromatherapy) may make breathing easier.

Prognosis
RSV infection usually runs its course in seven to
14 days. The cough may linger weeks longer. There are
no medications that can speed the body’s production
of antibodies against the virus. Opportunistic bacterial
infections that take advantage of a weakened
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Alveoli—Small air sacs or cavities in the lung that
give the tissue a honeycomb appearance and
expand its surface area for the exchange of oxygen
and carbon dioxide.
Antibody—A protein produced by specialized
white blood cells in response to the presence of a
foreign protein such as a virus. Antibodies help the
body fight infection.
Reye’s syndrome—A rare disorder in children that
follows a viral infection and is associated with a
reaction to aspirin. Its symptoms include vomiting,
damaged liver function, and swelling of the brain.

respiratory system may cause ear, sinus, and throat
infections or pneumonia.
Hospitalization and death are much more likely to
occur in children whose immune systems are weakened or who have underlying diseases of the lungs
and heart. People do not gain permanent immunity to
respiratory syncytial virus and can be infected many
times. Children who suffer repeated infections seem to
be more likely to develop asthma in later life.

Prevention
As of 1998 there are no vaccines against RSV.
Respiratory syncytial virus infection is so common
that prevention is impossible. However, steps can be
taken to reduce a child’s contact with the disease.
People with RSV symptoms should stay at least six
feet away from young children. Frequent handwashing, especially after contact with respiratory secretions, and the correct disposal of used tissues help
keep the disease from spreading. Parents should try
to keep their children under 18 month old away from
crowded environments–for example, shopping malls
during holiday seasons–where they are likely to come
in contact with older people who have only mild symptoms of the disease. Child care centers should regularly
disinfect surfaces that children touch.
Resources
PERIODICALS

Hemming, Val, et al. ‘‘Bracing for the Cold and Flu Season.’’
Patient Care 31 (September 1997): 47-54.

Tish Davidson, A.M.
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Respiratory syncytial virus infection



Restless legs syndrome



Central nervous system (CNS) abnormalities.
Several types of drugs have been found to reduce
the symptoms of RLS. Based on an understanding
of how these drugs work, theories have been developed to explain the cause of the disorder. Levodopa
and other drugs that correct problems with signal
transmission within the central nervous system
(CNS) can reduce the symptoms of RLS. It is therefore suspected that the source of RLS is a problem
related to signal transmission systems in the CNS.



Iron deficiency. The body stores iron in the form of
ferritin. There is a relationship between low levels of
iron (as ferritin) stored in the body and the occurrence of RLS. Studies have shown that older people
with RLS often have low levels of ferritin.
Supplements of iron sulfate have been shown to significantly reduce RLS symptoms for these patients.

Restless legs syndrome
Definition
Restless legs syndrome (RLS) is characterized by
unpleasant sensations in the limbs, usually the legs,
that occur at rest or before sleep and are relieved by
activity such as walking. These sensations are felt deep
within the legs and are described as creeping, crawling,
aching, or fidgety.

Description
Restless legs syndrome, also known as Ekbom
syndrome, Wittmaack-Ekbom syndrome, anxietas
tibiarum, or anxietas tibialis, affects up to 10–15%
of the population. Some studies show that RLS is
more common among elderly people. Almost half of
patients over age 60 who complain of insomnia are
diagnosed with RLS. In some cases, the patient has
another medical condition with which RLS is associated. In idiopathic RLS, no cause can be found. In
familial cases, RLS may be inherited from a close
relative, most likely a parent.

Causes and symptoms
Most people experience mild symptoms. They may
lie down to rest at the end of the day and, just before
sleep, will experience discomfort in their legs that
prompts them to stand up, massage the leg, or walk
briefly. Eighty-five percent of RLS patients either have
difficulty falling asleep or wake several times during the
night, and almost half experience daytime fatigue or
sleepiness. It is common for the symptoms to be intermittent. They may disappear for several months and
then return for no apparent reason. Two-thirds of
patients report that their symptoms become worse
with time. Some older patients claim to have had symptoms since they were in their early 20s, but were not
diagnosed until their 50s. Suspected under-diagnosis of
RLS may be attributed to the difficulty experienced by
patients in describing their symptoms.
More than 80% of patients with RLS experience
periodic limb movements in sleep (PLMS). These random movements of arms or legs may result in further
sleep disturbance and daytime fatigue. Most patients
have restless feelings in both legs, but only one leg may
be affected. Arms may be affected in nearly half of
patients.
There is no known cause for the disorder, but
recent research has focused on several key areas.
These include:
3200

Diagnosis
A careful history enables the physician to distinguish RLS from similar types of disorders that cause
night time discomfort in the limbs, such as muscle
cramps, burning feet syndrome, and damage to nerves
that detect sensations or cause movement
(polyneuropathy).
The most important tool the doctor has in diagnosis is the history obtained from the patient. There
are several common medical conditions that are
known to either cause or to be closely associated
with RLS. The doctor may link the patient’s symptoms to one of these conditions, which include anemia,
diabetes, disease of the spinal nerve roots (lumbosacral radiculopathy), Parkinson’s disease, late-stage
pregnancy, kidney failure (uremia), and complications
of stomach surgery. In order to identify or eliminate
such a primary cause, blood tests may be performed to
determine the presence of serum iron, ferritin, folate,
vitamin B 12, creatinine, and thyroid-stimulating hormones. The physician may also ask if symptoms are
present in any close family members, since it is common for RLS to run in families and this type is sometimes more difficult to treat.
In some cases, sleep studies such as polysomnography are undertaken to identify the presence of PLMS
that are reported to affect 70–80% of people who
suffer from RLS. The patient is often unaware of
these movements, since they may not cause him to
wake. However, the presence of PLMS with RLS can
leave the person more tired, because it interferes with
deep sleep. A patient who also displays evidence of
some neurologic disease may undergo electromyography (EMG). During EMG, a very small, thin needle is
GALE ENCYCLOPEDIA OF MEDICINE

Levodopa to cause daytime worsening of symptoms
(occurs in about 25% of patients). However, it is not
recommended as the first choice in drug therapy
since it causes a high rate of minor side effects.
Pergolide is often used only if Levodopa has been
discontinued.

Treatment
The first step in treatment is to treat existing conditions that are known to be associated with RLS and
that will be identified by blood tests. If the patient is
anemic, iron (iron sulfate) or vitamin supplements
(folate or vitamin B12) will be prescribed. If kidney
disease is identified as a cause, treatment of the kidney
problem will take priority.



High potency opioids. If the symptoms of RLS are
difficult to treat with the above medication, higher
dose opioids will be used. These include methadone
(Dolophine), oxycodone, and clonidine (Catapres,
Combipres, Dixarit). A significant disadvantage of
these drugs is risk of addiction.



Anticonvulsants. Some cases of RLS may be
improved by anticonvulsant drugs, such as carbamazepine (Tegretol).



Combination therapy. Some patients respond well to
combinations of drugs such as a benzodiazepine and
Levodopa.

Prescription drugs
In some people whose symptoms cannot be linked
to a treatable associated condition, drug therapy may
be necessary to provide relief and restore a normal
sleep pattern. Prescription drugs that are normally
used for RLS include:






Benzodiazepines and low-potency opioids. These
drugs are prescribed for use only on an ‘‘as needed’’
basis, for patients with mild RLS. Benzodiazepines
appear to reduce nighttime awakenings due to
PLMS. The benzodiazepine most commonly used
to treat RLS is clonazepam (Klonopin, Rivotril).
The main disadvantage of this drug type is that it
causes daytime drowsiness. It also causes unsteadiness that may lead to accidents, especially for an
elderly patient. Opioids are narcotic pain relievers.
Those commonly used for mild RLS are low potency
opioids, such as codeine (Tylenol #3) and propoxyphene (Darvocet). Studies have shown that these can
be successfully used in the treatment of RLS on a
long-term basis without risk of addiction. However,
narcotics can cause constipation and difficulty
urinating.
Levodopa (L-dopa) and carbidopa (Sinemet).
Levodopa is the drug most commonly used to treat
moderate or severe RLS. It acts by supplying a chemical called dopamine to the brain. It is often taken
in conjunction with carbidopa to prevent or decrease
side effects. Although it is effective against RLS,
levodopa may also causes a worsening of symptoms
during the afternoon or early evening in 50–80% of
patients. This phenomenon is known as ‘‘restless legs
augmentation,’’ and if it occurs, the physician will
probably discontinue Levodopa for a brief period
while an alternate drug is used. Levodopa can often
be reintroduced after a short break.
Pergolide (Permax). Pergolide acts on the same part
of the brain as Levodopa. It is less likely than

GALE ENCYCLOPEDIA OF MEDICINE

Many drugs have been investigated for treatment
of RLS, but it seems as though the perfect therapy has
not yet been found. However, careful monitoring of
side effects and good communication between patient
and doctor can result in a flexible program of therapy
that minimizes side effects and maximizes
effectiveness.

Alternative treatment
It is likely that the best alternative therapy will
combine both conventional and alternative
approaches. Levodopa may be combined with a therapy that relieves pain, relaxes muscles, or focuses in
general on the nervous system and the brain. Any such
combined therapy that allows a reduction in dosage of
levodopa is advantageous, since this will reduce the
likelihood of unacceptable levels of drug side effects.
Of course, the physician who prescribes the medication should monitor any combined therapy.
Alternative methods may include:


Acupuncture. Patients who also suffer from rheumatoid arthritis may especially benefit from acupuncture to relieve RLS symptoms. Acupuncture is
believed to be effective in arthritis treatment and
may also stimulate those parts of the brain that are
involved in RLS.



Homeopathy. Homeopaths believe that disorders of
the nervous system are especially important because
the brain controls so many other bodily functions.
The remedy is tailored to the individual patient and is
based on individual symptoms as well as the general
symptoms of RLS.
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Restless legs syndrome

inserted into the muscle and electrical activity of the
muscle is recorded. A doctor or technician usually
performs this test at a hospital outpatient department.

Restrictive cardiomyopathy

KEY TERMS
Anemia—A condition that affects the size and
number of red blood cells. It often results from
lack of iron or certain B vitamins and may be treated with iron or vitamin supplements.
Insomnia—Trouble sleeping. People who suffer
from RLS often lose sleep either because they
spend time walking to relieve discomfort or
because they have PLMS, which causes them to
wake often during the night.
Periodic limb movements in sleep (PLMS)—
Random movements of the arms or legs that occur
at regular intervals of time during sleep.



Reflexology. Reflexologists claim that the brain,
head, and spine all respond to indirect massage of
specific parts of the feet.



Nutritional supplements. Supplementation of the
diet with vitamin E, calcium, magnesium, and folic
acid may be helpful for people with RLS.

Some alternative methods may treat the associated condition that is suspected to cause restless
legs. These include:




Anemia or low ferritin levels. Chinese medicine will
emphasize stimulation of the spleen as a means of
improving blood circulation and vitamin absorption.
Other treatments may include acupuncture and herbal therapies, such as ginseng (Panax ginseng) for
anemia-related fatigue.
Late-stage pregnancy. There are few conventional
therapies available to pregnant women, since most
of the drugs prescribed are not recommended for use
during pregnancy. Pregnant women may benefit
from alternative techniques that focus on body
work, including yoga, reflexology, and acupuncture.

Prognosis
RLS usually does not indicate the onset of other
neurological disease. It may remain static, although
two-thirds of patients get worse with time. The symptoms usually progress gradually. Treatment with
Levodopa is effective in moderate to severe cases that
may include significant PLMS. However, this drug
produces significant side effects, and continued successful treatment may depend on carefully monitored
use of combination drug therapy. The prognosis is
usually best if RLS symptoms are recent and can be
3202

traced to another treatable condition that is associated
with RLS. Some associated conditions are not treatable. In these cases, such as for rheumatoid arthritis,
alternative therapies such as acupuncture may be
helpful.

Prevention
Diet is key in preventing RLS. A preventive diet
will include an adequate intake of iron and the B
vitamins, especially B12 and folic acid. Strict vegetarians should take vitamin supplements to obtain sufficient vitamin B12. Ferrous gluconate may be easier on
the digestive system than ferrous sulfate, if iron supplements are prescribed. Some medications may cause
symptoms of RLS. Patients should check with their
doctor about these possible side effects, especially if
symptoms first occur after starting a new medication.
Caffeine, alcohol, and nicotine use should be minimized or eliminated. Even a hot bath before bed has
been shown to prevent symptoms for some sufferers.
Resources
PERIODICALS

Silber, Michael H. ‘‘Concise Review for Primary-Care
Physicians. Restless Legs Syndrome.’’ Mayo Clinical
Proceedings 72 (March 1997): 261-264.
ORGANIZATIONS

Restless Legs Syndrome Foundation. 1904 Banbury Road,
Raleigh, NC 27608-4428. (919) 781-4428. <http://
www.rls.org>.

Ann M. Haren

Restrictive cardiomyopathy
Definition
Cardiomyopathy is an ongoing disease process
that damages the muscle wall of the lower chambers
of the heart. Restrictive cardiomyopathy is a form of
cardiomyopathy in which the walls of the heart
become rigid.

Description
Restrictive cardiomyopathy is the least common
type of cardiomyopathy in the United States. The
stiffened heart walls cannot stretch properly to allow
enough blood to fill the ventricles between heartbeats.
As the stiffening worsens, heart failure occurs. The
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Restrictive cardiomyopathy can be caused by a
number of diseases. Often, the cause is unknown.
The rigidity of the heart walls may be caused by fibrosis, the replacement of muscle cells with tough, fibrous
tissue. In some disorders, proteins and other substances are deposited in the heart wall. Amyloidosis is
the accumulation of a protein material, called amyloid, in the tissue of the heart wall and other organs. In
hemochromatosis, there is too much iron in the body
and some of the excess iron can build up in the heart.
Sarcoidosis causes the formation of many small
lesions, called granulomas, in the heart wall and
other tissues of the body. These granulomas contain
inflammatory white blood cells and other cells that
decrease the flexibility of the heart.
People with restrictive cardiomyopathy usually
feel tired and weak, and have shortness of breath,
especially during exercise. If blood is backing up in
the circulation they may also experience edema (large
amounts of fluid in tissues) of the legs and feet.

Diagnosis
The diagnosis is usually based on a physical
examination, echocardiography, and other tests as
needed. The physician listens to the heart with a
stethoscope to detect abnormal heart rhythms and
heart sounds.
Echocardiography uses sound waves to make
images of the heart. These images provide information
about the structures of the heart and its heart valves.
Echocardiography can also be used to find out how
much blood the heart is pumping. It determines the
amount of blood in the ventricle, called the ventricular
volume, and the amount of blood the ventricle pumps
each time it beats, called the ejection fraction. A
healthy heart pumps at least one half the amount of
blood in the left ventricle with each heartbeat.
Computed tomography scan (CT scan) and magnetic resonance imaging (MRI) are imaging tests that
can also provide information about the structure of
the heart. However, these tests are rarely needed for
diagnosis.
Cardiac catheterization may be needed to confirm
a diagnosis or cause. In cardiac catheterization, a
small tube called a catheter is inserted into an artery
and passed into the heart. It is used to measure
pressure in the heart and the amount of blood
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Amyloidosis—Build up of amyloid, a protein substance, in tissues of the body, including the heart.
Cardiac catheterization—A diagnostic test for
evaluating heart disease; a catheter is inserted into
an artery and passed into the heart.
Edema—Swelling caused by fluid buildup in
tissues.
Fibrosis—Replacement of normal tissue with
tough, fibrous tissue.
Hemochromatosis—A disease in which there is too
much iron in the body; iron deposits can build up in
the heart muscle and other tissues.
Sarcoidosis—A chronic disease causing the formation of many small lesions called granulomas in the
heart wall and other tissues of the body.

pumped by the heart. A small tissue sample (biopsy)
of the heart muscle can be removed through the
catheter for microscopic examination. Fibrous tissue
or deposits in the heart muscle can be identified in
this biopsy.

Treatment
There is no effective treatment for restrictive cardiomyopathy. Treatment of a causative disease may
reduce or stop the damage to the heart, but existing
damage cannot be reversed. Medications may be used
to lessen the workload on the heart and to control the
heart rhythm. Drugs normally used to treat other
types of cardiomyopathy and heart failure may cause
problems for patients with restrictive cardiomyopathy. For example, medicines that reduce the heart’s
workload may lower blood pressure too much.
A heart transplant may be necessary for patients
who develop severe heart failure.

Prognosis
The prognosis for patients with restrictive cardiomyopathy is poor. If the disease process causing the
problem can be treated, the damage to the heart muscle may be stopped. Also, medicines may relieve symptoms. However, for most patients, restrictive
cardiomyopathy eventually causes heart failure. A
heart transplant may be necessary when heart failure
becomes too severe to treat with medicines.
3203

Restrictive cardiomyopathy

blood backs up into the blood vessels, causing fluid
buildup in tissues (congestion and edema).

Reticulocyte count

Prevention

Description

Obtaining early treatment for diseases that might
cause restrictive cardiomyopathy might prevent or
slow the development of heart wall stiffness. Anyone
experiencing symptoms of shortness of breath, tiredness, and weakness should see a physician.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
Texas Heart Institute. Heart Information Service. P.O. Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Toni Rizzo

Reticulocyte count
Definition
A reticulocyte count is a blood test performed to
assess the body’s production of immature red blood
cells (reticulocytes). A reticulocyte count is usually
performed when patients are evaluated for anemia
and response to its treatment. It is sometimes called a
retic count.

Purpose
Diagnosis
A reticulocyte count provides information about
the rate at which the bone marrow is producing red
cells. A normal count means that the production is
adequate; a decreased count means it is not. This information helps determine whether a lack of red cells in an
anemic person is caused by a bone marrow problem, by
excessive bleeding, or by red cell destruction.
Monitoring
The test is also used to monitor the response of
bone marrow response to treatment for anemia. The
reticulocyte count rises within days if the treatment is
successful. It is also used following bone marrow
transplant to evaluate the new marrow’s cell
production.
3204

Reticulocytes were first described as transitional
forms of red blood cells by Wilhelm H. Erb in 1865. A
red cell begins in the bone marrow as a large bluish cell
filled with ribonucleic acid (RNA). As the cell
matures, it shrinks. Its color gradually changes from
blue to pink as its load of oxygen-carrying protein
(hemoglobin) increases and the RNA decreases. The
center of the cell (nucleus) becomes clumped. It is
expelled three days before the cell leaves the bone
marrow. The cell is now a reticulocyte. On its fourth
and final day of maturation, the reticulocyte enters
the bloodstream. One day later, it is a mature red
blood cell.
The first step in a retic count is drawing the
patient’s blood sample. About 17 oz (5 ml) of blood
is withdrawn from a vein into a vacuum tube. The
procedure, which is called a venipuncture, takes
about five minutes.
After the sample is collected, the blood is mixed
with a dye (methylene blue) in a test tube. The RNA
remaining in the reticulocytes picks up a deep blue
stain. Drops of the mixture are smeared on slides and
examined under a microscope. Reticulocytes appear
as cells containing dark blue granules or a blue network. The laboratory technologist counts 1,000 red
cells, keeping track of the number of reticulocytes. The
number of reticulocytes is reported as a percentage of
the total red cells. When the red cell count is low, the
percentage of reticulocytes is inaccurately high, suggesting that more reticulocytes are present than there
are in reality. The percentage is mathematically corrected for greater accuracy. This figure is called the
corrected reticulocyte count or reticulocyte index.
Reticulocyte counts can also be done on automated instruments, such as flow cytometers, using
fluorescent stains. These instruments are able to detect
small changes in the reticulocyte count because they
count a larger number of cells (10,000–50,000).

Preparation
The doctor should make a note of any prescription medications that the patient is taking. Some drugs
lower the red blood cell count.

Aftercare
Aftercare consists of routine care of the area
around the puncture mark. Pressure is applied for a
few seconds and the wound is covered with a
bandage.
GALE ENCYCLOPEDIA OF MEDICINE

Anemia—A condition marked by a decrease in the
number or size of red blood cells
Methylene blue—A dye that is used to stain the
blood cells for the reticulocyte count.
Reticulocyte—An immature red blood cell.

of vision in one eye. Occlusion of its branches causes
loss of vision in only a portion of the field of vision.

Description
Retinal artery occlusion (RAO) occurs when the
central retinal artery, the main source of blood supply
to the retina, or one of its branches becomes blocked.

Causes and symptoms
The main causes of RAO are the following:

Risks
The primary risk is mild dizziness and the possibility of a bruise or swelling in the area where the blood
was drawn. The patient can apply moist warm
compresses.



embolism (the sudden obstruction of a blood vessel
by a blood clot)



atherosclerotic disease that results in the progressive
narrowing of the arteries over time



endarteritis (the chronic inflammation of the inner
layer of arteries)



angiospasm (a spasmodic contraction of a blood
vessel with increase in blood pressure)

Normal results
Adults have reticulocyte counts of 0.5–2.5%.
Women and children usually have higher reticulocyte
counts than men.

Abnormal results
A low reticulocyte count indicates that the bone
marrow is not producing a normal number of red
blood cells. Low production may be caused by a lack
of vitamin B12, folic acid, or iron in the diet; or by an
illness affecting the bone marrow (for example, cancer). Further tests are needed to diagnose the specific
cause.
The reticulocyte count rises when the bone marrow makes more red cells in response to blood loss or
treatment of anemia.
Resources

The most common symptom of RAO is an acute,
painless loss of vision in one eye. The degree of loss
depends on the location of the occlusion. If the occlusion occurs in the central artery of the retina, damage
usually results in complete loss of vision in the affected
eye. If occlusion occurs in a branch artery, vision loss
will be partial and may even go unnoticed if only a
section of the peripheral vision is affected.
People affected by RAO typically have high blood
pressure, heart disease, or diabetes as an underlying
condition. Other conditions that may increase the risk
of RAO include high cholesterol and glaucoma.
Incidence is slightly more common in men and in
people age 60 or older.

Diagnosis

PERIODICALS

Rowan, R. M., et al. ‘‘The Reticulocyte Count: Progress
Towards the Resurrection of a Useful Clinical Test.’’
Clinical and Laboratory Haematology 18, no. 1 (1996): 3-8.

Nancy J. Nordenson

Retinal artery occlusion
Definition
Retinal artery occlusion refers to the closure of the
central retinal artery and usually results in complete loss
GALE ENCYCLOPEDIA OF MEDICINE

RAO is diagnosed by examination of the retina
with an ophtalmoscope.

Treatment
Central retinal artery occlusion (CRAO) is an emergency. If treatment begins within an hour, the patient
has the highest possibility of regaining vision in the
affected eye, although complete restoration is unlikely.
A common treatment is inhalation of carbon
dioxide so as to dilate the retinal vessels and move
the occlusion from the central retinal artery to a
branch artery. This movement reduces the area of the
retina affected and may restore a certain amount of
vision. Eyeball massage may also be performed, also in
3205

Retinal artery occlusion

KEY TERMS

Retinal detachment

KEY TERMS
Angiospasm—Spasmodic contraction of a blood
vessel with increase in blood pressure.
Arterioles—Small blood vessels that carry arterial
(oxygenated) blood.
Atherosclerotic disease—The progressive narrowing and hardening of the arteries over time.
Central retinal artery—A branch of the ophthalmic
artery that supplies blood to the retina and branches
to form the arterioles of the retina.
Embolism—The sudden obstruction of a blood vessel by a blood clot.
Endarteritis—Chronic inflammation of the inner
layer of arteries.
Hyperbaric oxygenation—Administration of oxygen in a compression chamber at an ambient pressure greater than 1 atmosphere, in order to increase
the amount of oxygen in organs and tissues.
Occlusion—Momentary complete closure of some
area or channel of the body.
Ophthalmic artery —The artery supplying the eye
and adjacent structures with blood.
Ophthalmoscope—An instrument used for viewing
the inside of the eye that consists of a concave
mirror with a hole in the middle through which
the physician examines the eye, and a light source
that is reflected into the eye by the mirror.
Retina—Light sensitive layer of the eye, that consists of four major layers: the outer neural layer,
containing nerve cells and blood vessels, the photoreceptor layer, a single layer that contains the light
sensing rods and cones, the pigmented retinal
epithelium (PRE) and the choroid, consisting of
connective tissue and capillaries.

an effort to remove the occlusion. The physician may
also consider puncturing the eyeball.
Drug therapy includes the use of carbonic anhydrase inhibitors to reduce the internal eye pressure and
enhance movement of the occlusion. Both of the treatments would be used within the first 24 hours of
noticeable vision loss.

Alternative treatment
Hyperbaric oxygen therapy may be beneficial if
started within 90 minutes of the onset of symptoms.
3206

Some studies indicate a 40% improvement of visual
acuity using this method.

Prognosis
The prognosis for central retinal visual acuity is
poor with only about one-third of patients recovering
useful vision. The longest delay in getting treatment
that has been associated with significant visual recovery was approximately 72 hours.
Branch retinal artery occlusions (BRAO) have a
recovery rate of 80% where vision is restored to 20/40
or better.

Prevention
Individuals affected by underlying conditions
such as high blood pressure, heart disease, diabetes,
glaucoma, and elevated cholesterol should treat their
conditions appropriately to minimize the possibility of
a retinal artery occlusion.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. P.O. Box 7424, San
Francisco, CA 94120-7424. (415) 561-8500. Fax: (415)
561-8533. <http://www.eyenet.org/>.
American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) DIABETES.
<http://www.diabetes.org/>.
American Heart Association National Center. 7272
Greenville Avenue, Dallas, Texas 75231. (877) 2424277. <http://www.americanheart.org/>.
CliniWeb International. <http://www.ohsu.edu/cliniweb/
C11/C11.768.html>.

Gary Gilles

Retinal detachment
Definition
Retinal detachment is movement of the transparent
sensory part of the retina away from the outer pigmented layer of the retina. In other words, the moving away
of the retina from the outer wall of the eyeball.

Description
There are three layers of the eyeball. The outer,
tough, white sclera. Lining the sclera is the choroid, a
GALE ENCYCLOPEDIA OF MEDICINE

Retinal detachment

Cornea
Vitreous
humor

Lens
Retina
Sclera

Detached retina

Normal eye

Retinal detachment refers to the movement of the retina away from the inner wall of the eyeball, resulting in a sudden defect in
vision. Persons suffering from diabetes have a high incidence of developing retinal disease. (Illustration by Electronic Illustrators
Group.)

thin membrane that supplies nutrients to part of the
retina. The innermost layer is the retina.
The retina is the light-sensitive membrane that
receives images and transmits them to the brain. It is
made up of several layers. One layer contains the
photoreceptors. The photoreceptors, the rods and
cones, send the visual message to the brain. Between
the photoreceptor layer (also called the sensory layer)
and the choroid is the pigmented epithelium.
The vitreous is a clear gel-like substance that fills
up most of the inner space of the eyeball. It lies behind
the lens and is in contact with the retina.
A retinal detachment occurs between the two outermost layers of the retina–the photoreceptor layer
and the outermost pigmented epithelium. Because
the choroid supplies the photoreceptors with nutrients, a detachment can basically starve the photoreceptors. If a detachment is not repaired within 24–72
hours, permanent damage may occur.



Retinal detachment may be spontaneous. This
occurs more often in the elderly or in very nearsighted (myopic) eyes.



Cataract surgery causes retinal detachment 2% of
the time.



Tumors can cause the retina to detach.

Retinal detachment will cause a sudden defect in
vision. It may look as if a curtain or shadow has just
descended before the eye. If most of the retina is
detached, there may be only a small hole of vision
remaining. If just a part of the retina is involved,
there will be a blind spot that may not even be noticed.
It is often associated with floaters–little dark spots that
float across the eye and can be mistaken for flies in the
room. There may also be flashes of light. Anyone
experiencing a sudden onset of flashes and/or floaters
should contact their eye doctor immediately, as this
may signal a detachment.

Diagnosis
Causes and symptoms
Several conditions may cause retinal detachment:


Scarring or shrinkage of the vitreous can pull the
retina inward.



Small tears in the retina allow liquid to seep behind
the retina and push it forward.



Injury to the eye can simply knock the retina loose.



Bleeding behind the retina, most often due to
diabetic retinopathy or injury, can push it
forward.

GALE ENCYCLOPEDIA OF MEDICINE

If the eye is clear–that is, if there is no clouding of
the liquids inside the eye–the detachment can be seen
by looking into the eye with a hand-held instrument
called an ophthalmoscope. To evaluate the blood vessels in the retina, a fluorescent dye (fluorescein) may be
injected into a vein and photographed with ultraviolet
light as it passes through the retina. Further studies
may include computed tomography scan (CT scan),
magnetic resonance imaging (MRI), or ultrasound
study. Other lenses may be used to examine the back
of the eyes. One example is binocular indirect ophthalmoscopy. The doctor dilates the patient’s eyes with
3207

Retinal hemorrhage

KEY TERMS
Cauterize—To damage with heat or cold so that
tissues shrink. It is an effective way to stop bleeding.
Diabetic retinopathy—Disease that damages the
blood vessels in the back of the eye caused by
diabetes.
Saline—A salt solution equivalent to that in the
body–0.9% salt in water.

eyedrops and then examines the back of the eyes with a
handheld lens.

Treatment
Reattaching the retina to the inner surface of the
eye requires making a scar that will hold it in place and
then bringing the retina close to the scarred area. The
scar can be made from the outside, through the sclera,
using either a laser or a freezing cold probe (cryopexy).
Bringing the retina close to the scar can be done in two
ways. A tiny belt tightened around the eyeball will
bring the sclera in until it reaches the retina. This
procedure is called scleral buckling and may be done
under general anesthesia. Using this procedure permits
the repair of retinal detachments without entering the
eyeball. Sometimes, the eye must be entered to pump
in air or gas, forcing the retina outward against the
sclera and its scar. This is called pneumatic retinopexy
and can generally be done under local anesthesia.
If all else fails, and especially if there is disease in
the vitreous, the vitreous may have to be removed in a
procedure called vitrectomy. This can be done through
tiny holes in the eye, through which equally tiny
instruments are placed to suck out the vitreous and
replace it with saline, a salt solution. The procedure
must maintain pressure inside the eye so that the eye
does not collapse.

Prognosis
Retinal reattachment has an 80–90% success rate.

Prevention
In diseases such as diabetes, with a high incidence
of retinal disease, routine eye examinations can detect
early changes. Early treatment can prevent both progressing to detachment and blindness from other
events like hemorrhage. The most common problem
3208

is weakness of blood vessels that causes them to break
down and bleed. When enough vessels have been
damaged, new vessels grow to replace them. These
new vessels may grow into the vitreous, producing
blind spots and scarring. The scarring can in turn
pull the retina loose. Other diseases can cause the
tiny holes and tears in the retina through which fluid
can leak. Preventive treatment uses a laser to cauterize
the blood vessels, so that they do not bleed and the
holes, so they do not leak.
Good control of diabetes can help prevent diabetic eye disease. Blood pressure control can prevent
hypertension from damaging the retinal blood vessels.
Eye protection can prevent direct injury to the eyes.
Regular eye exams can also detect changes that the
patient may not be aware of. This is important for
patients with high myopia who may be more prone to
detachment.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.

J. Ricker Polsdorfer, MD

Retinal hemorrhage
Definition
Retinal hemorrhage is the abnormal bleeding of
the blood vessels in the retina, the membrane in the
back of the eye.

Description
The retina is the part of the eye that converts light
into nerve signals that are processed by the brain into
visual images. The retina is the inside surface of the
back of the eye, consisting of millions of densely
arranged, light-sensitive cells called rods and cones.
Blood flow to the retina is maintained by the retinal
vein and artery, and a dense network of small blood
vessels (capillaries) supplies the area with circulation.
These blood vessels can become damaged by injury
and disease and may bleed (hemorrhage) and cause
temporary or permanent loss of visual accuracy.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Retinal hemorrhages can be caused by injuries,
usually forceful blows to the head during accidents
and falls, as well as by adverse health conditions. In
infants, retinal hemorrhage is frequently associated
with child abuse and has been termed shaken baby
syndrome. A condition called retinopathy of prematurity occurs in prematurely born infants or infants with
low birth weights. When children are born prematurely, the blood vessels in the eye may not have had
time to fully develop and may become damaged easily,
leaking or hemorrhaging. The condition must be
determined by an opthalmologist, as the symptoms
are not readily observable.
Diabetic retinopathy is a common eye problem
associated with diabetes. Diabetes, by stressing the
circulatory system, can cause damage, including
hemorrhaging, to the small blood vessels of the retina.
Non-proliferative retinopathy occurs when the
damaged or leaking blood vessels do not spread.
Symptoms of this disorder include vision spots, floaters (floating areas of blurred vision), decreased or loss
of vision, or loss of fine vision for detailed activities
such as reading. Proliferative retinopathy occurs when
new blood vessels begin to form in damaged areas of
the retina, and may lead to spots, floaters, decreased
vision, or sudden loss of vision. Sudden vision loss
may occur if one of the newly formed blood vessels
ruptures. Due to increased pressure in the area, the
retina may detach from the back of the eye, a serious
condition and a cause of blindness.
People with high blood pressure (hypertension)
may develop hypertensive retinopathy, in which
blood vessels in the retina become damaged from
increased blood pressure. Symptoms are typically not
pronounced, but blurred or decreased vision may be
caused by the disorder.
Central serous retinopathy is a condition in which
the vessels behind the retina leak and cause fluid to
collect in small blisters behind the retina. Symptoms
include sudden blurry areas in the vision, blind spots,
distorted vision areas, and loss of vision. This condition is most common in males between 20 and 50 years
of age.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Diabetes—Disease in which the body does not
properly produce or use insulin, resulting in fluctuating blood sugar levels.
Hypertension—Condition caused by high blood
pressure.
Opthalmologist—Physician specializing in the
diagnosis and treatment of disorders of the eye.

Diagnosis
Diagnosis of retinopathy is performed by an
opthalmologist, particularly one who specializes in
disorders of the retina (retinal specialist). The opthalmologist may perform an opthalmoscopy, using an
instrument called an opthalmoscope to examine the
inside of the eye. For a detailed view of the blood
vessels of the retina, a fluorescein angiography test
might be performed, in which a florescent dye is
injected into the patient’s bloodstream and photographs record the status of the blood vessels in the
retina. Vision tests, patient history, and blood tests
might also be ordered by the diagnosing physician.

Treatment
Laser surgery by an opthalmologist is a common
treatment for retinal hemorrhages, in which a laser
beam is used to remove or seal off damaged or bleeding blood vessels in the retina. Some vision loss occurs
with this technique. For retinal hemorrhages associated with diabetes and high blood pressure, treating
the overall condition is required.

Alternative treatment
Alternative treatment of retinal hemorrhages
focuses on providing nutrients to strengthen and heal
the injured blood vessels. Nutritional supplements
include antioxidant vitamins A, C, and E; vitamin
B-complex including B6 and B12; the mineral zinc;
and essential fatty acids including omega-3 from fish
oil and flaxseed oil. Herbal supplements include bilberry, grape seed extract, pine bark extract (pycnogenol), and lutein.

Prognosis
For retinal hemorrhages associated with retinopathy of prematurity, nearly 85 percent of cases heal
3209

Retinal hemorrhage

Because the cells of the retina are so dense and sensitive, even small injuries to the blood vessels can translate into vision problems. Diseases that affect the
health of the circulatory system, such as diabetes and
high blood pressure, also affect the blood vessels of the
eye. Damage to the blood vessels in the retina, including hemorrhage, is termed retinopathy.

Retinal vein occlusion

without treatment. Diabetic retinopathy is the leading cause of blindness for those between 20 and 65
years old in the U.S. Diabetic retinopathy typically
takes years to develop in people with diabetes, but
occurs in nearly 80 percent of those with diabetes for
over 20 years and who are treated with insulin.
Regular monitoring and treatments can slow the
degeneration of the eye, while advanced cases of the
disorder lead to blindness. Retinopathies requiring
laser treatment have a partial loss of vision due to
the surgery. For hypertensive retinopathy, most
vision problems go away when high blood pressure
is treated and lowered. The majority of cases of central sirous retinopathy disappear after three to four
months, and full vision generally returns within six
months, although recurrence of the disorder is
common.

Prevention
The first step in sound prevention is for people
with vision problems, including visual spots, flashes
or floaters in the vision, and loss or distortion of
visual accuracy, to see an opthalmologist as soon as
possible. To prevent complications of retinal hemorrhages in infants, the prevention includes regular
prenatal care and monitoring of infants with high
risks of the disorder (born prematurely or with
weight less than four pounds and six ounces). For
diabetic retinopathy, control of blood sugar and
blood pressure fluctuations is necessary, as well as
frequently scheduled eye exams by an opthalmologist. For retinal hemorrhages associated with hypertension, controlling high blood pressure through diet,
exercise, and stress reduction is recommended.
Central sirous retinopathy has been associated with
high stress levels, so preventative care for this disorder includes stress management practices.
Resources
BOOKS

Abel, Robert.The Eye Care Revolution: Prevent and Reverse
Common Vision Problems. Kensington, 1999.
Anshel, Jeffrey.Smart Medicine for Your Eyes. Avery
Publishing, 1999.
Cassel, Gary H.The Eye Book: A Compete Guide to Eye
Disorders and Health. Johns Hopkins University Press,
1998.
Grossman, Marc.Natural Eye Care: An Encyclopedia.
McGraw Hill, 1999.

National Eye Institute. 2020 Vision Place, Bethesda, MD
20892-3655. (301) 496-5248. <http://
www.nei.nih.gov>.

Douglas Dupler

Retinal vein occlusion
Definition
Retinal vein occlusion refers to the closure of the
central retinal vein that drains the retina or to that of
one of its branches.

Description
Retinal vein occlusion (RVO) occurs when the
central retinal vein, the blood vessel that drains the
retina, or one of its branches becomes blocked. RVO
may be categorized by the anatomy of the occluded
vein and the degree of ischemia produced. The two
major RVO types are central retinal vein occlusion
(CRVO) and branch retinal vein occlusion (BRVO).
CRVO has been diagnosed in patients as young as nine
months to patients of 90 years. The age of affected
individuals is usually low to mid 60s. Approximately
90% of patients are over 50 at the time of diagnosis,
with 57% of them being male and 43% being female.
BRVO accounts for some 30% of all vein occlusions.

Causes and symptoms
CRVO is a painless loss of vision that can be
caused by a swollen optic disk, the small area in the
retina where the optic nerve enters the eye, by dilated
retinal veins, and by retinal hemorrhages. CRVO is
also called venous stasis retinopathy, or hemorrhagic
retinopathy.
In BRVO, the superotemporal branch vein is the
most often affected vessel. Retinal hemorrhages follows, often occurring at the crossing of two vessels
near the optic disk. Initially the hemorrhage may be
extensive and underlie the fovea.
The exact cause of RVO is not yet identified, but
the following mechanisms been proposed:


external compression between the central connective
strand and the cribriform plate



venous disease



blood clot formation

ORGANIZATIONS

American Academy of Ophthalmology. P.O. Box 7424, San
Francisco, CA 94120. (415) 561-8500. <http://
www.aao.org>.
3210

GALE ENCYCLOPEDIA OF MEDICINE



hypertension



hyperlipidemia



diabetes mellitus



hyperviscosity



hypercoagulability



glaucoma



trauma

Diagnosis
A complete physical evaluation is recommended
for CRVO and BRVO, including complete blood tests,
and glucose tolerance test (for non-diabetics). In the
case of a head injury when bleeding around the optic
nerve is a possibility, an MRI may be performed.

Treatment
Following a patient with RVO is vital. Patients
should be seen at least monthly for the first three
months to monitor for signs of other complications,
such as the abnormal formation of blood vessels
(neovascularization) in the iris of the eye or
glaucoma.
The treatment for retinal vein occlusion varies for
each case and should be given based on the doctor’s
best recommendation. Although treatments for occlusion itself are limited, surgical treatment of the occlusion provides an option.
Treatments may include anticoagulants with
heparin, bishydroxycoumarin, and streptokinase.
When the blood is highly viscous, dilution of the
blood may be useful. Ideally, an alternate pathway is
needed to allow venous drainage. Recent reports published in 1999 suggest that use of a laser to create a
retinal choroidal hole may be useful to treat CRVO.
Laser therapy depends on the type of occlusion. The
management of laser therapy should be controlled by
an ophthalmologist.

Alternative treatment
There are no documented alternative treatment
methods.

Prognosis
The outlook for people with RVO is fairly good
whether it is treated early or not. With no treatment at
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anticoagultants—Drugs that act by lowering the
capacity of the blood to coagulate, thus facilitating
removal of blood clots.
Central retinal vein—Central blood vessel and its
branches that drains the retina.
Cribriform plate—The horizontal bone plate perforated with several holes for the passage of olfactory nerve filaments from the nasal cavity.
Fovea—A small area of the retina responsible for
acute vision.
Glaucoma—A group of eye diseases characterized
by an increase in eyeball pressure.
Hyperlipidemia—A general term for elevated
concentrations of any or all of the lipids in the
plasma.
Iris—The contractile diaphragm located in the fluid
in front of the lens of the eye and is perforated by
the eye pupil.
Ischemia—A state of low oxygen in a tissue usually
due to organ dysfunction.
Neovascularization—Abnormal or excessive formation of blood vessels as in some retinal
disorders.
Occlusion—Momentary complete closure of some
area or channel of the body.
Optic disk—The small area in the retina where the
optic nerve enters the eye that is not sensitive to
light. Also called the blind spot.
Retina—Light sensitive layer of the eye, that
consists of four major layers: the outer neural
layer, containing nerve cells and blood vessels,
the photoreceptor layer, a single layer that contains the light sensing rods and cones, the pigmented retinal epithelium (PRE) and the
choroid, consisting of connective tissue and
capillaries.

all, approximately 60% of all patients recover 20/40
vision or better within a year.

Prevention
Retinal vein occlusion is difficult to prevent
because the exact cause is still uncertain. Ethnic factors may play a role since in the UK the disease is rare
in Asians and West Indians.
3211

Retinal vein occlusion

Conditions associated with RVO risk include:

Retinitis pigmentosa

Resources
BOOKS

Spaide, Richard F., MD. Diseases of the Retina and Vitreous.
New York: W.B. Saunders Co., 1999.

Michael Sherwin Walston
Ronald Watson, PhD

Retinitis pigmentosa
Definition
Retinitis pigmentosa (RP) refers to a group of
inherited disorders that slowly lead to blindness due
to abnormalities of the photoreceptors (primarily the
rods) in the retina.

Description
The retina lines the interior surface of the back of
the eye. The retina is made up of several layers. One
layer contains two types of photoreceptor cells
referred to as the rods and cones. The cones are
responsible for sharp, central vision and color vision
and are primarily located in a small area of the retina
called the fovea. The area surrounding the fovea contains the rods, which are necessary for peripheral
vision and night vision (scotopic vision). The number
of rods increases in the periphery. The rod and cone
photoreceptors convert light into electrical impulses
and send the message to the brain via the optic nerve.
Another layer of the retina is called the retinal pigmented epithelium (RPE).
In RP, the photoreceptors (primarily the rods)
begin to deteriorate and lose their ability to function.
Because the rods are primarily affected, it becomes
harder to see in dim light, thus causing a loss of night
vision. As the condition worsens, peripheral vision
disappears, which results in tunnel vision. The ability
to see color is eventually lost. In the late stages of the
disease, there is only a small area of central vision
remaining. Ultimately, this too is lost.
There are many forms of retinitis pigmentosa.
Sometimes the disorder is classified by the age of
onset or the inheritance pattern. RP can also accompany other conditions. This entry discusses ‘‘nonsyndromic’’ RP, the type that is not associated with
other organ or tissue dysfunction.
Approximately 100,000 Americans have RP. It is
estimated to affect about one in every 4,000 Americans
3212

and Europeans. For other parts of the world, there are
no published data. Nor is there any known ethnic
difference in the occurrence of RP.

Causes and symptoms
Retinitis pigmentosa is an inherited disease that
has many different modes of inheritance. It is known
to be caused by more than 100 different genetic mutations. RP, with any inheritance pattern, may be either
familial (multiple family members affected) or isolated
(only one affected person). In the non-sex-linked, or
autosomal, form, it can either be a dominant or recessive trait. In the sex-linked form, called x-linked recessive, it is a recessive trait. This x-linked form is more
severe than the autosomal forms. Two rare forms of
RP are the digenic and mitochondrial forms.
Isolated RP cases represent 10–40% of all cases.
Some of these cases may be the result of new gene
mutations (changes in the genes). Other isolated
cases are those in which the person has a relative
with a mutation in the gene, but the relative is not
affected by the condition.
Autosomal dominant RP (AdRP) occurs in about
15–25% of affected individuals. At least 12 different
genes have been identified as causing AdRP. People
with AdRP will usually have an affected parent. The
risk for affected siblings or children is 50%.
Autosomal recessive RP (ArRP) occurs in about
5–20% of affected individuals. More than 16 genes
have been identified that cause this type of RP. In
ArRP, each parent of the affected person is a carrier
of an abnormal gene that causes RP. Neither of these
carrier parents is affected. There is a two-thirds chance
that an unaffected sibling is a carrier of RP. All of the
children of an affected person would be a carrier of the
ArRP gene.
Five to 15% of individuals with RP have x-linked
recessive RP (XLRP). Six different genes have been
identified as the cause of this type of RP. Usually in
this type of inheritance, males are affected carriers,
while females are unaffected carriers or have a milder
form of the disease. The mother may be a carrier of the
mutation on the X-chromosome. It is also possible
that a new mutation can occur for the first time in an
affected person. For families with one affected male,
there is a mathematical formula called the Baysean
analysis that can be applied to the family history. It
takes into account the number of unaffected males to
determine whether a female is likely to be a carrier or
not. If a mother is a carrier, her children have a 50%
chance of inheriting the RP gene. For affected males,
GALE ENCYCLOPEDIA OF MEDICINE

Ophthalmoscope—An instrument, with special
lighting, designed to view structures in the back of
the eye.

the eye, and the output is measured on a special instrument called an oscilloscope. The functional assessments of visual fields, visual acuity, or color vision
may also be performed.
A fundus camera image showing the degeneration of the
retina due to retinitis pigmentosa. The pattern of dark spots
across the retina corresponds to the extent of loss of vision.
(Custom Medical Stock Photo. Reproduced by permission.)

all of their daughters will be carriers but none of their
sons will be affected.
The digenic form of RP occurs when the affected
person has inherited one copy of an altered ROM1
gene from one parent and one copy of an altered
peripherin/RDS gene from the other parent. The parents are asymptomatic. Mitochondrial inheritance
occurs when the gene mutation is in a mitochondrial
gene. People with this type of RP have progressive
hearing loss and mild myopathy. Both of these types
of RP are very rare.
The first symptoms, a loss of night vision followed
by a loss of peripheral vision, usually begin in early
adolescence or young adulthood. Occasionally, the
loss of the ability to see color occurs before the loss
of peripheral vision. Another possible symptom is
seeing twinkling lights or small flashes of lights.

Diagnosis
When a person complains of a loss of night vision,
a doctor will examine the interior of the eye with an
ophthalmoscope to determine if there are changes in
the retina. For people with advanced RP, the condition is characterized by the presence of clumps of black
pigment in the inner retina (intraretinal). However, the
appearance of the retina is not enough for an RP
diagnosis since there are other disorders that may
give the retina a similar appearance. There are also
other reasons someone may have night blindness.
Consequently, certain electrodiagnostic tests must be
performed. An electroretinogram (ERG) determines
the functional status of the photoreceptors by exposing the retina to light. The ERG uses a contact lens in
GALE ENCYCLOPEDIA OF MEDICINE

The diagnosis of RP can be established when the
following criteria are met:


rod dysfunction measured by dark adaptation test or
ERG,



progressive loss in photoreceptor function,



loss of peripheral (side) vision,



both eyes affected (bilaterality).

Molecular genetic testing is available on a research
basis. Prenatal diagnosis for this condition has not yet
been achieved.

Treatment
There are no medications or surgery to treat
RP. However, researchers continue to seek possible
treatments. In 2004, scientists injected stem cells to
the back of mouse eyes and stopped retinal degeneration. Scientists are also exploring the possibility
of retinal transplantation. Some doctors believe
vitamins A and E will slightly slow the progression
of the disease in some people. However, large doses
of certain vitamins may be toxic and affected individuals should speak to their doctors before taking
supplements.
If a person with RP must be exposed to bright
sunlight, some doctors recommend wearing dark sunglasses to reduce the effect on the retina. Affected
people should talk to their eye doctors about the correct lenses to wear outdoors.
Because there is no cure for RP, the affected
person should be monitored for visual function and
counseled about low-vision aids (for example, fieldexpansion devices). Genetic counseling is also appropriate. A three-generation family history with
attention to other relatives with possible RP can help
to clarify the inheritance pattern. For some people
however, the inheritance pattern cannot be discerned.
3213

Retinitis pigmentosa

KEY TERMS

Retinoblastoma

Prognosis

Description

There is no known cure for RP, which will eventually lead to blindness. The more severe forms will
lead to blindness sooner than milder forms.
Resources
PERIODICALS

‘‘Grant Boosts RP Research Into Transplantation.’’
Ophthalmology TImes August 1, 2004: 6.
‘‘Stem Cells Delivered Into Back of Eye Hold Promise for
People With Retinitis Pigmentosa, Other Retinal
Degenerations; Potential Treatment for Untreatable
Blindness Shows Promise in Mice.’’ Ascribe Health
News Service September 15, 2004.
ORGANIZATIONS

American Academy of Ophthalmology. PO Box 7424, San
Francisco, CA 94120-7424. (415) 561-8500. <http://
www.eyenet.org>.
American Association of the Deaf-Blind. 814 Thayer Ave.,
Suite 302, Silver Spring, MD 20910. (301) 588-6545.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
Foundation Fighting Blindness. Executive Plaza 1, Suite
800, 11350 McCormick Rd., Hunt Valley, MD 21031.
(888) 394-3937. <http://www.blindness.org>.
National Retinitis Pigmentosa Foundation. 11350
McCormick Rd., Executive Plaza 1, Suite 800, Hung
Valley, MD 21031-1014. (800) 683-5555. <http://
www.blindness.org>.
Prevent Blindness America. 500 East Remington Rd.,
Schaumburg, IL 60173. (800) 331-2020. <http://
www.prevent-blindness.org>.
OTHER

Genetic Alliance. <http://www.geneticalliance.org>.
National Federation of the Blind. <http://www.nfb.org>.
‘‘OMIM—Online Mendelian Inheritance in Man.’’ National
Center for Biotechnology Information. <http://
www.ncbi.nlm.nih.gov/Omim/searchomim.html>.
Retinitis Pigmentosa International. <http://
www.rpinternational.org>.

Amy Vance, MS, CGC
Dorothy Elinor Stonely
Teresa G. Odle

Retinoblastoma
Definition
Retinoblastoma is a malignant tumor of the retina
that occurs predominantly in young children.
3214

The eye has three layers, the sclera, the choroid,
and the retina. The sclera is the outer protective white
coating of the eye. The choroid is the middle layer and
contains blood vessels that nourish the eye. The front
portion of the choroid is colored and is called the iris.
The opening in the iris is called the pupil. The pupil is
responsible for allowing light into the eye and usually
appears black. When the pupil is exposed to bright
light it contracts (closes), and when it is exposed to low
light conditions it dilates (opens) so that the appropriate amount of light enters the eye. Light that enters
through the pupil hits the lens of the eye. The lens then
focuses the light onto the retina, the innermost of the
three layers. The job of the retina is to transform the
light into information that can be transmitted to
the optic nerve, which will transmit this information
to the brain. It is through this process that people are
able to see the world around them.
Occasionally a tumor, called a retinoblastoma,
will develop in the retina of the eye. Usually this
tumor forms in young children but it can occasionally
occur in adults. Most people with retinoblastoma
develop only one tumor (unifocal) in only one eye
(unilateral). Some, however, develop multiple tumors
(multifocal) in one or both eyes. When retinoblastoma
occurs independently in both eyes, it is then called
bilateral retinoblastoma.
Occasionally, children with retinoblastoma
develop trilateral retinoblastoma. Trilateral retinoblastoma results from the development of an independent brain tumor that often forms in a part of the brain
called the pineal gland. In order for retinoblastoma to
be classified as trilateral retinoblastoma, the tumor
must have developed independently and not as the
result of the spread of the retinal cancer. The prognosis
for trilateral retinoblastoma is quite poor.
The retinal tumor which characterizes retinoblastoma is malignant, meaning that it can metastasize
(spread) to other parts of the eye and eventually
other parts of the body. In most cases, however, retinoblastoma is diagnosed before it spreads past the eye
to other parts of the body (intraocular) and the prognosis is quite good. The prognosis is poorer if the
cancer has spread beyond the eye (extraocular).
Retinoblastoma can be inherited or can arise
spontaneously. Approximately 40% of people with
retinoblastoma have an inherited form of the condition and approximately 60% have a sporadic (not
inherited) form. Individuals with multiple independent tumors, bilateral retinoblastoma, or trilateral
GALE ENCYCLOPEDIA OF MEDICINE

Approximately 1 in 15,000 to 1 in 30,000 infants in
Western countries are born with retinoblastoma, making it the most common childhood eye cancer. It is,
however, a relatively rare childhood cancer and
accounts for approximately 3% of childhood cancers.
The American Academy of Ophthalmology estimates
that 300–350 cases of retinoblastoma occur in the
United States each year.
Retinoblastoma is found mainly in children under
the age of five but can occasionally be seen in older
children and adults. Retinoblastoma is found in individuals of all ethnic backgrounds and is found equally
frequently in males and females. The incidence of
bilaterial retinoblastoma in the United States is
thought to be slightly higher among black children
than among either Caucasian or Asian American
children.

Causes and symptoms
Causes
Retinoblastoma is caused by changes in or
absence of a gene called RB1. RB1 is located on the
long arm of chromosome 13. Cells of the body, with
the exception of the egg and sperm cells, contain 23
pairs of chromosomes. All of the cells of the body
excluding the egg and the sperm cells are called the
somatic cells. The somatic cells contain two of each
chromosome 13 and therefore two copies of the RB1
gene. Each egg and sperm cell contains only one copy
of chromosome and therefore only one copy of the
RB1 gene.
RB1 produces a tumor suppressor protein that
normally helps to regulate the cell cycle of cells such
as those of the retina. A normal cell of the retina goes
through a growth cycle during which it produces new
cells. Genes such as tumor suppressor genes tightly
regulate this growth cycle.
Cells that lose control of their cell cycle and replicate out of control are called cancer cells. These
undergo many cell divisions, often at a quicker rate
than normal cells, and do not have a limited lifespan.
A group of adjacent cancer cells can form a mass
called a tumor. Malignant (cancerous) tumors can
spread to other parts of the body. A malignant
tumor of the retina (retinoblastoma) can result when
just one retinal cell looses control of it cell cycle and
replicates out of control.
Normally the tumor suppressor protein produced
by RB1 prevents a retinal cell from becoming
GALE ENCYCLOPEDIA OF MEDICINE

cancerous. Each RB1 gene produces tumor suppressor
protein. Only one functioning RB1 gene in a retinal
cell is necessary to prevent the cell from becoming
cancerous. If both RB1 genes in a retinal cell become
non-functional, then a retinal cell can become cancerous and retinoblastoma can result. An RB1 gene is
non-functional when it is changed or missing (deleted)
and no longer produces normal tumor suppressor
protein.
Approximately 40% of people with retinoblastoma have inherited a non-functional or deleted RB1
gene from either their mother or father. Therefore,
they have a changed/deleted RB1 gene in every
somatic cell. A person with an inherited missing or
non-functional RB1 gene will develop a retinal
tumor if the remaining RB1 gene becomes changed
or deleted in a retinal cell. The remaining RB1 gene
can become non-functional when exposed to environmental triggers such as chemicals and radiation. In
most cases, however, the triggers are unknown.
Approximately 90% of people who inherit a changed
or missing RB1 gene will develop retinoblastoma.
People with an inherited form of retinoblastoma
are more likely to have a tumor in both eyes (bilateral)
and are more likely to have more than one independent tumor (multifocal) in one or both eyes. The average
age of onset for the inherited form of retinoblastoma is
one year, which is earlier than the sporadic form of
retinoblastoma. Although most people with the inherited form of retinoblastoma develop bilateral tumors,
approximately 15% of people with a tumor in only one
eye (unilateral) are affected with an inherited form of
retinoblastoma.
A person with an inherited missing or nonfunctional RB1 gene has a 50% chance of passing on
this abnormal gene to his or her offspring. The chance
that their children will inherit the changed/deleted
gene and actually develop retinoblastoma is approximately 45%.
Some people with retinoblastoma have inherited a
non-functioning or missing RB1 gene from either their
mother or father even though their parents have never
developed retinoblastoma. It is possible that one parent has a changed or missing RB1 gene in every
somatic cell but has not developed retinoblastoma
because their remaining RB1 gene has remained functional. It is also possible that the parent had developed
a retinal tumor that was destroyed by the body. In
other cases, one parent has two normal RB1 genes in
every somatic cell, but some of their egg or sperm cells
contain a changed or missing RB1 gene. This is called
gonadal mosaicism.
3215

Retinoblastoma

retinoblastoma are more likely to be affected with the
inherited form of retinoblastoma.

Retinoblastoma

Retinoblastoma can also result when both RB1
genes become spontaneously changed or deleted in a
retinal cell but the RB1 genes are normal in all the
other cells of the body. Approximately 60% of people
with retinoblastoma have this type of disease, called
sporadic retinoblastoma. A person with sporadic retinoblastoma does not have a higher chance of having
children with the disease. Their relatives do not have a
higher risk of developing retinoblastoma themselves
or having children who develop retinoblastoma.
Sporadic retinoblastoma is usually unifocal and has
an average age of onset of approximately two years.
Symptoms
The most common symptom of retinoblastoma is
leukocoria. Leukocoria results when the pupil reflects
a white color rather than the normal black or red color
that is seen on a flash photograph. It is often most
obvious in flash photographs; since the pupil is
exposed to a lot of light and the duration of the exposure is so short, the pupil does not have time to constrict. Children with retinoblastoma can also have
problems seeing and this can cause them to appear
cross-eyed (strabismus). People with retinoblastoma
may also experience red, painful, and irritated eyes,
inflamed tissue around the eye, enlarged pupils, and
possibly different-colored eyes.

Diagnosis
Children who have symptoms of retinoblastoma
are usually first evaluated by their pediatrician. The
pediatrician will often perform a red reflex test to
diagnose or confirm leukocoria. Prior to this test the
doctor inserts medicated eye drops into the child’s eyes
so that the pupils will remain dilated and not contract
when exposed to bright light. The doctor then examines the eyes with an ophthalmoscope, which shines a
bright light into the eyes and allows the doctor to
check for leukocoria. Leukocoria can also be diagnosed by taking a flash Polaroid photograph of a
patient who has been in a dark room for three to five
minutes.
If the pediatrician suspects retinoblastoma on the
basis of these evaluations, he or she will most likely
refer the patient to an ophthalmologist (eye doctor)
who has experience with retinoblastoma. The
ophthalmologist will examine the eye using an indirect ophthalmoscope. The opthalmoscope shines a
bright light into the eye, which helps the doctor to
visualize the retina. This evaluation is usually done
under general anesthetic, although some very young
or older patients may not require it. Prior to the
3216

examination, medicated drops are put into the eyes
to dilate the pupils, and anesthetic drops may also be
used. A metal clip is used to keep the eyes open during
the evaluation. During the examination, a cotton
swab or a metal instrument with a flattened tip is
used to press on the outer lens of the eye so that a
better view of the front areas of the retina can be
obtained. Sketches or photographs of the tumor as
seen through the ophthalmoscope are taken during
the procedure.
An ultrasound evaluation is used to confirm the
presence of the tumor and to evaluate its size.
Computed axial tomography (CT scan) is used to
determine whether the tumor has spread outside of
the eye and to the brain. Sometimes magnetic resonance imaging (MRI) is also used to look at the eyes,
eye sockets, and the brain to see if the cancer has
spread.
In most cases the cancer has not spread beyond
the eye, and other evaluations are unnecessary. If the
cancer appears to have spread beyond the eye, then
other assessments such as a blood test, spinal tap
(lumbar puncture), and/or bone marrow biopsy may
be recommended. During a spinal tap, a needle is
inserted between the vertebrae of the spinal column
and a small sample of the fluid surrounding the spinal
cord is obtained. In a bone marrow biopsy, a small
amount of tissue (bone marrow) is taken from inside
the hip or breast bone for examination.
Genetic testing
Establishing whether someone is affected with an
inherited or non-inherited form of retinoblastoma can
help to ascertain whether other family members such
as siblings, cousins, and offspring are at increased risk
for developing retinoblastoma. It can also sometimes
help guide treatment choices, since patients with an
inherited form of retinoblastoma may be at increased
risk for developing recurrent tumors or other types of
cancers, particularly when treated with radiation. It is
helpful for the families of a child diagnosed with retinoblastoma to meet with a genetic specialist such as a
genetic counselor and/or geneticist. These specialists
can help to ascertain the chances that the retinoblastoma is inherited and facilitate genetic testing if
desired.
If a patient with unilateral or bilateral retinoblastoma has a relative or relatives with retinoblastoma, it
can be assumed that they have an inherited form of
retinoblastoma. However, it cannot be assumed that a
patient without a family history of the disease has a
sporadic form.
GALE ENCYCLOPEDIA OF MEDICINE

The only way to establish whether someone has an
inherited form of retinoblastoma is to see if the retinoblastoma gene is changed or deleted in the blood cells
obtained from a blood sample. Approximately 5–8%
of individuals with retinoblastoma possess a chromosomal abnormality involving the RB1 gene that can be
detected by looking at their chromosomes under the
microscope. The chromosomes can be seen by obtaining a blood sample. If this type of chromosomal
abnormality is detected in a child, then analysis of
the parents’ chromosomes should be performed. If
one of the parents possesses a chromosomal abnormality, then they are at higher risk for having other
offspring with retinoblastoma. Chromosome testing
would be recommended for the blood relatives of the
parent with the abnormality.
Usually, however, a chromosomal abnormality is
not detected in a child with retinoblastoma. In this
case, specialized DNA tests that look for small RB1
gene changes need to be performed on the blood cells.
DNA testing can be difficult, time consuming, and
expensive, since there are many possible RB1 gene
changes that can cause the gene to become
nonfunctional.
If a sample of tumor is available, then it is recommended that DNA testing be performed on the tumor
cells prior to DNA testing of the blood cells. This
testing can usually identify the gene changes/deletions
in the RB1 genes that caused the tumor to develop. In
some cases, RB1 gene changes/deletions are not found
in the tumor cells (as of 2001, approximately 20% of
RB1 gene changes or deletions are not detectable). In
these cases, DNA testing of the blood cells will not be
able to ascertain whether someone is affected with an
inherited or non-inherited form of retinoblastoma.
If the changes in both RB1 genes are detected in
the tumor cell, then these same changes can be looked
for in the blood cells. If an RB1 gene is deleted or
changed in all of the blood cells tested, the patient
can be assumed to have been born with a changed/
deleted RB1 gene in all of their cells. This person has a
50% chance of passing the RB1 gene change/deletion
on to his or her children. Most of the time, this change/
deletion has been inherited from a parent.
Occasionally the gene change/deletion occurred spontaneously in the original cell that was formed when the
egg and sperm came together at conception (de novo).
GALE ENCYCLOPEDIA OF MEDICINE

Retinoblastoma

Even when there is no family history, most cases
of bilateral and trilateral retinoblastoma are inherited,
as are most cases of unilateral, multifocal retinoblastoma. However, only 15% of unilateral, unifocal retinoblastoma cases are inherited.

This child’s right eye is completely covered with a tumor
associated with retinoblastoma. (Custom Medical Stock
Photo. Reproduced by permission.)

If an RB1 gene change/deletion is found in all of
the blood cells tested, both parents should undergo
blood testing to check for the same RB1 gene change/
deletion. If the RB1 gene change/deletion is identified
in one of the parents, it can be assumed that the
retinoblastoma was inherited and that siblings have a
50% chance of inheriting the altered gene. More distant blood relatives of the parent with the identified
RB1 gene change/deletion may also be at risk for
developing retinoblastoma. Siblings and other relatives could undergo DNA testing to see if they have
inherited the RB1 gene change/deletion.
If the RB1 gene change/deletion is not identified
in either parent, then the results can be more difficult
to interpret. In this case, there is a 90–94% chance that
the retinoblastoma was not inherited.
In some cases, a person with retinoblastoma will
have an RB1 gene change/deletion detected in some of
their blood cells and not others. It can be assumed that
this person did not inherit the retinoblastoma from
either parent. Siblings and other relatives would therefore not be at increased risk for developing retinoblastoma. Offspring would be at increased risk since some
of the egg or sperm cells could have the changed/
deleted RB1 gene. The risks to offspring would probably be less than 50%.
In families where there are multiple family members affected with retinoblastoma, blood samples from
3217

Retinoblastoma

multiple family members are often analyzed and compared through DNA testing. Ninety-five percent of the
time, this type of analysis is able to detect patterns in
the DNA that are associated with a changed RB1 gene
in that particular family. When a pattern is detected,
at-risk relatives can be tested to establish whether they
have inherited an RB1 gene change/deletion.
PRENATAL TESTING. If chromosome or DNA testing identifies an RB1 gene/deletion in someone’s
blood cells, then prenatal testing can be performed
on this person’s offspring. An amniocentesis or chorionic villus sampling can be used to obtain fetal cells
which can be analyzed for the RB1 gene change/deletion or chromosomal abnormality.

Treatment
A number of different classification (staging) systems are used to establish the severity of retinoblastoma and aid in choosing an appropriate treatment
plan. The most widely used staging system is the
Reese-Ellsworth system. This system is used to classify
intraocular tumors and predict which tumors are
favorable enough that sight can be maintained. The
Reese-Ellsworth classification system is divided into:


Group I (very favorable for maintenance of sight):
small solitary or multiple tumors, less than 6.4 mm in
size (1 inch = 25.4 mm), located at or below the
equator of the eye



Group II (favorable for maintenance of sight): solitary or multiple tumors, 6.4–16 mm in size, located at
or behind the equator of the eye



Group III (possible for maintenance of sight): any
tumor located in front of the equator of the eye, or a
solitary tumor larger than 16 mm in size and located
behind the equator of the eye



Group IV (unfavorable for maintenance of sight):
multiple tumors, some larger than 16 mm in size, or
any tumor extending in front of the outer rim of the
retina (ora serrata)



Group V (very unfavorable for maintenance of
sight): large tumors involving more than half of the
retina, or vitreous seeding, in which small pieces of
tumor are broken off and floating around the inside
of the eye

When choosing a treatment plan, the first important criteria to ascertain is whether the cancer is localized within the eye (intralocular) or has spread to
other parts of the body (extralocular). An intraocular
retinoblastoma may only involve the retina or could
involve other parts of the eye. An extraocular
3218

retinoblastoma could involve only the tissues around
the eye or could result from the spread of cancer to the
brain or other parts of the body.
It is also important to establish whether the cancer
is unilateral (one eye) or bilateral (both eyes), multifocal or unifocal. In order for the tumors to be considered multifocal, they must have arisen
independently and not as the result of the spread of
cancer cells. It is also important to check for trilateral
retinoblastoma.
Treatments
The treatment chosen depends on the size and
number of tumors, whether the cancer is unilateral or
bilateral, and whether the cancer has spread to other
parts of the body. The goal of treatment is to cure the
cancer and prevent as much loss of vision as possible.
Since the late 1990s, doctors treating patients with
retinoblastoma have tended to avoid enucleation and
external beam radiation therapy whenever possible, in
favor of chemotherapy to reduce the tumor in addition
to focal therapies. Improved methods of chemoreduction have led to increasing success in saving patients’
eyes, often with some visual function.
TREATMENT OF INTRAOCULAR TUMORS. Surgical
removal of the affected eye (enucleation) is used
when the tumor(s) are so large and extensive that
preservation of sight is not possible. This surgery is
performed under general anesthetic and usually takes
less than an hour. Most children who have undergone
this surgery can leave the hospital on the same day. A
temporary ball is placed in the eye socket after the
surgery. Approximately three weeks after the operation, a plastic artificial eye (prosthesis) that looks like
the normal eye is inserted into the eye socket.

Radiation therapy is often used for treatment of
large tumors when preservation of sight is possible.
External beam radiation therapy involves focusing a
beam of radiation on the eye. If the tumor has not
spread extensively, the radiation beam can be focused
on the cancerous retinal cells. If the cancer is extensive,
radiation treatment of the entire eye may be necessary.
External beam radiation is performed on an outpatient basis and usually occurs over a period of three to
four weeks. Some children may need sedatives prior to
the treatment. This type of therapy can result in a
temporary loss of a patch of hair on the back of the
head and a small area of ‘‘sun-burned’’ skin. Longterm side effects of radiation treatment can include
cataracts, vision problems, bleeding from the retina,
and decreased growth of the bones on the side of the
head. People with an inherited form of retinoblastoma
GALE ENCYCLOPEDIA OF MEDICINE

cryotherapy, thermotherapy, chemotherapy, and brachytherapy may be considered.

Photocoagulation therapy is often used in conjunction with radiation therapy but may be used
alone to treat small tumors that are located on the
back of the eye. Photocoagulation involves using a
laser to destroy the cancer cells. This type of treatment
is done under local or general anesthesia and is usually
not associated with post-procedural pain.

eyes, radiation therapy of both eyes may be recommended. Smaller, more localized tumors can sometimes be treated by local therapies such as
cryotherapy, photocoagulation therapy, thermotherapy or brachytherapy. Some centers may use chemotherapy in place of radiation therapy when the
tumors are too large to be treated by local therapies
or are found over the optic nerve of the eye. Many
centers are moving away from radiation treatment and
toward chemotherapy because it is less likely to induce
future tumors. Enucleation is performed on the more
severely affected eye if sight cannot be preserved in
both.

Thermotherapy is also often used in conjunction
with radiation therapy or drug therapy (chemotherapy). Thermotherapy involves the use of heat to help
shrink tumor cells. The heat is either used on the whole
eye or localized to the tumor area. It is done under
local or general anesthesia and is usually not painful.
Cryotherapy is a treatment often used in conjunction with radiation therapy but can also be used alone
on small tumors located on the front part of the retina.
Cryotherapy involves the use of intense cold to destroy
cancer cells and can result in harmless, temporary
swelling of the external eye and eyelids that can last
for up to five days. Eye drops or ointment are sometimes provided to reduce the swelling.
Brachytherapy involves the application of radioactive material to the outer surface of the eye at the
base of the tumor. It is generally used for tumors of
medium size. A patient undergoing this type of procedure is usually hospitalized for three to seven days.
During that time, he or she undergoes one surgery to
attach the radioactive material and one surgery to
remove it. Eye drops are often administered for three
to four weeks following the operation to prevent
inflammation and infection. The long-term side effects
of this treatment can include cataracts and damage to
the retina, which can lead to impaired vision.
Intravenous treatment with one or more drugs
(chemotherapy) is often used for treatment of both
large and small tumors. Chemotherapy is sometimes
used to shrink tumors prior to other treatments such
as radiation therapy or brachytherapy. Occasionally,
it is also used alone to treat very small tumors.
TREATMENT OF INTRAOCULAR AND UNILATERAL
RETINOBLASTOMA. Often, by the time that unilateral

retinoblastoma is diagnosed, the tumor is so large that
useful vision cannot be preserved. In these cases
removal of the eye (enucleation) is the treatment of
choice. Other therapies are unnecessary if enucleation
is used to treat intraocular unilateral retinoblastoma.
If the tumor is small enough, other therapies such as
external beam radiation therapy, photocoagulation,
GALE ENCYCLOPEDIA OF MEDICINE

TREATMENT OF INTRAOCULAR AND BILATERAL
RETINOBLASTOMA. If vision can be preserved in both

EXTRAOCULAR RETINOBLASTOMA. There is no proven effective therapy for the treatment of extraocular
retinoblastomas. Commonly, radiation treatment of
the eyes and chemotherapy is provided.

Alternative treatment
There are no alternative or complementary therapies specific to the treatment of retinoblastoma. Since
most people diagnosed with retinoblastoma are small
children, most drug-based alternative therapies
designed to treat general cancer would not be recommended. Many specialists would, however, stress the
importance of establishing a well-balanced diet,
including certain fruits, vegetables, and vitamin supplements, to ensure that the body is strengthened in its
fight against cancer. Some advocate the use of visualization strategies, in which patients would visualize
the immune cells of their body attacking and destroying the cancer cells.

Prognosis
Individuals with intraocular retinoblastoma who
do not have trilateral retinoblastoma usually have a
good survival rate with a 90% chance of disease-free
survival for five years. Those with extraocular retinoblastoma have less than a 10% chance of disease-free
survival for the same amount of time. Trilateral retinoblastoma generally has a very poor prognosis.
Patients with trilateral retinoblastoma who receive
treatment have an average survival rate of approximately eight months, while those who remain
untreated have an average survival rate of approximately one month. Patients with trilateral retinoblastoma who are asymptomatic at the time of diagnosis
3219

Retinoblastoma

have an increased risk of developing other cancers as a
result of this therapy. Some consideration should
therefore be given to alternative treatment therapies
for those with an inherited form of retinoblastoma.

Retinoblastoma

may have a better prognosis then those who experience symptoms.
Patients with an inherited form of unilateral retinoblastoma have a 70% chance of developing retinoblastoma in the other eye. Retinoblastoma reoccurs in
the other eye in approximately 5% of people with a
non-inherited form of retinoblastoma, so it is advisable for even these patients to be closely monitored.
People with an inherited form of retinoblastoma who
have not undergone radiation treatment have approximately a 26% chance of developing cancer in another
part of the body within 50 years of the initial diagnosis.
Those with an inherited form who have undergone
radiation treatment have a 58% chance of developing
a secondary cancer by 50 years after the initial diagnosis. Most of the secondary cancers are skin cancers,
bone tumors (osteosarcomas), and soft-tissue sarcomas. Soft-tissue sarcomas are malignant tumors of the
muscle, nerves, joints, blood vessels, deep skin tissues,
or fat. The prognosis for retinoblastoma patients who
develop secondary cancers, however, is very poor as of
the early 2000s.
Survivors of retinoblastoma are likely to have
visual field defects after their cancer treatment is completed, most commonly scotomas, which are areas of
lost or depressed vision within an area of normal
vision. The size and type of these visual defects are
determined by the size and type of the original tumor
and the form of therapy used to treat it.

Prevention
Although retinoblastoma cannot be prevented,
appropriate screening and surveillance should be
applied to all at-risk individuals to ensure that the
tumor(s) are diagnosed at an early stage. The earlier
the diagnosis, the more likely that an eye can be salvaged and vision maintained.
Screening of people diagnosed with retinoblastoma
Children who have been diagnosed with retinoblastoma should receive periodic dilated retinal examinations until the age of five. Young children will need
to undergo these evaluations under anesthetic. After
five years of age, periodic eye examinations are recommended. It may be advisable for patients with bilateral
retinoblastoma or an inherited form of retinoblastoma
to undergo periodic screening for the brain tumors
found in trilateral retinoblastoma. There are no specific screening protocols designed to detect non-ocular
tumors. All lumps and complaints of bone pain, however, should be thoroughly evaluated.
3220

Screening of relatives
When a child is diagnosed with retinoblastoma,
it is recommended that parents and siblings receive
a dilated retinal examination by an ophthalmologist who is experienced in the diagnosis and treatment of the disease. It is also recommended that
siblings continue to undergo periodic retinal examinations under anesthetic until they are three years
of age. From three to seven years of age, periodic
eye examinations are recommended. The retinal
examinations can be avoided if DNA testing indicates that the patient has a non-inherited form of
retinoblastoma or if the sibling has not inherited
the RB1 gene change/deletion. Any relatives who
are found through DNA testing to have inherited
an RB1 gene change/deletion should undergo the
same surveillance procedures as siblings.
The children of someone diagnosed with retinoblastoma should also undergo periodic retinal
examinations under anesthetic. Retinal surveillance
should be performed unless DNA testing proves
that their child does not possess the RB1 gene
change/deletion. If desired, prenatal detection of
tumors using ultrasound may also be performed.
During the ultrasound procedure, a hand-held
instrument is placed on the maternal abdomen or
inserted vaginally. The ultrasound produces sound
waves that are reflected back from the body structures of the fetus, producing a picture that can be
seen on a video screen. If a tumor is detected
through this evaluation, the affected baby may be
delivered a couple of weeks earlier. This can allow
for earlier intervention and treatment.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Retinoblastoma.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
PERIODICALS

Abramson, D. H., M. R. Melson, and C. Servodidio.
‘‘Visual Fields in Retinoblastoma Survivors.’’
Archives of Ophthalmology 122 (September 2004):
1324–1330.
Aerts, I., H. Pacquement, F. Doz, et al. ‘‘Outcome of
Second Malignancies after Retinoblastoma: A
Retrospective Analysis of 25 Patients Treated at the
Institut Curie.’’ European Journal of Cancer 40 (July
2004): 1522–1529.
Lohmann, D. R., and B. L. Gallie. ‘‘Retinoblastoma:
Revisiting the Model Prototype of Inherited
Cancer.’’ American Journal of Medical Genetics, Part
GALE ENCYCLOPEDIA OF MEDICINE

Amniocentesis—Prenatal testing performed at 16 to
20 weeks of pregnancy that involves inserting a needle
through the abdomen of a pregnant mother and obtaining a small sample of fluid from the amniotic sack,
which contains the fetus. Often is used to obtain a sample of the fetus’ cells for biochemical or DNA testing.
Benign tumor—An abnormal proliferation of cells
that does not spread to other parts of the body.
Bilateral—Affecting both eyes.
Brachytherapy—Cancer treatment that involves the
application of radioactive material to the site of the
tumor.
Cryotherapy—Cancer treatment in which the tumor
is destroyed by exposure to intense cold.
Chromosome—A microscopic structure found
within each cell of the body, made of a complex of
proteins and DNA.
Chorionic villus sampling (CVS)—Prenatal testing
performed at 10 to 12 weeks of pregnancy, which
involves inserting a catheter through the vagina of a
pregnant mother or inserting a needle through the
abdomen of the mother and obtaining a sample of
placenta. Often is used to obtain a sample of the
fetus’ cells for biochemical or DNA testing.
DNA (deoxyribonucleic acid)—The hereditary
material that makes up genes; influences the development and functioning of the body.
DNA testing—Testing for a change or changes in a
gene or genes.
Enucleation—Surgical removal of the eye.
Equator—Imaginary line encircling the eyeball and
dividing the eye into a front and back half.
Extraocular retinoblastoma—Cancer that has spread
from the eye to other parts of the body.
Gene—A building block of inheritance, made up of a
compound called DNA (deoxyribonucleic acid) and
containing the instructions for the production of a
particular protein. Each gene is found in a specific
location on a chromosome.

C: Seminars in Medical Genetics 129 (August 15,
2004): 23–28.
Provenzale, J. M., S. Gururangan, and G. Klintworth.
‘‘Trilateral Retinoblastoma: Clinical and Radiologic
Progression.’’ AJR: American Journal of Roentgenology
183 (August 2004): 505–511.
GALE ENCYCLOPEDIA OF MEDICINE

Intraocular retinoblastoma—Cancer that is limited to
the eye and has not spread to other parts of the body.
Malignant tumor—An abnormal proliferation of cells
that can spread to other sites.
Multifocal—More than one tumor present.
Ophthalmologist—Physician specializing in the diseases of the eye.
Optic nerve—The part of the eye which contains nerve
fibers that transmit signals from the eye to the brain.
Oncologist—A physician specializing in the diagnosis and treatment of cancer
Photocoagulation—Cancer treatment in which the
tumor is destroyed by an intense beam of laser light.
Prenatal testing—Testing for a disease such as a
genetic condition in an unborn baby.
Protein—A substance produced by a gene that is
involved in creating the traits of the human body,
such as hair and eye color, or is involved in controlling the basic functions of the human body, such as
control of the cell cycle.
Retina—The light-sensitive layer of the eye that
receives images and sends them to the brain.
Scotoma—An area of lost or depressed vision within
the visual field surrounded by an area of normal
vision. Survivors of retinoblastoma frequently
develop scotomas.
Somatic cells—All the cells of the body with the
exception of the egg and sperm cells.
Tumor—A growth of tissue resulting from the uncontrolled proliferation of cells.
Tumor-suppressor gene—Gene involved in controlling normal cell growth and preventing cancer.
Unifocal—Only one tumor present in one eye.
Unilateral—Affecting only one eye.
Vitreous—The transparent gel that fills the back part
of the eye.
Vitreous seeding—When small pieces of tumor have
broken off and are floating around the vitreous.

Shields, C. L., A. Mashayeki, J. Cater, et al. ‘‘Chemoreduction
for Retinoblastoma. Analysis of Tumor Control and Risks
for Recurrence in 457 Tumors.’’ American Journal of
Ophthalmology 138 (September 2004): 329–337.
Shields, C. L., and J. A. Shields. ‘‘Diagnosis and
Management of Retinoblastoma.’’ Cancer Control 11
(September-October 2004): 317–327.
3221

Retinoblastoma

KEY TERMS

Retinopathies

ORGANIZATIONS

American Academy of Ophthalmology (AAO). P. O. Box
7424, San Francisco, CA 94120-7424. (415) 561-8500.
Fax: (415) 561-8533. <http://www.aao.org>.
Institute for Families with Blind Children. PO Box 54700,
Mail Stop 111, Los Angeles, CA 90054-0700. (213) 6694649.
National Retinoblastoma Parents Group. PO Box 317,
Watertown, MA 02471. (800) 562-6265. Fax: (617) 9727444. napvi@perkins.pvt.k12.ma.us.
Retinoblastoma International. 4650 Sunset Blvd., Mail Stop
#88, Los Angeles, CA 90027. (323) 669-2299. info@
retinoblastoma.net. <http://www.retinoblastoma.net/
rbi/index_rbi.htm>.
Retinoblastoma Society. Saint Bartholomew’s Hospital,
London, UK EC1A 7BE. Phone: 020 7600 3309 Fax:
020 7600 8579. <http://ds.dial.pipex.com/rbinfo>.
OTHER

Abramson, David, and Camille Servodidio. ‘‘A Parent’s
Guide to Understanding Retinoblastoma.’’ June 20,
2001. <http://www.retinoblastoma.com/guide/
guide.html>.
Kid’s Eye Cancer. June 20, 2001. <http://
www.kidseyecancer.org>.
Lohmann, Dietmar, N. Bornfeld, B. Horsthemke, and
E. Passarge. ‘‘Retinoblastoma.’’ Gene Clinics. July 17,
2000. [cited June 20, 2001]. <http://www.geneclinics.org/profiles/retinoblastoma>.
McCusick, Victor. ‘‘Retinoblastoma; RB1.’’ Online Mendelian
Inheritance in Man. February 14, 2001. [cited June 20,
2001. <http://www.ncbi.nlm.nih.gov/Omim>.
‘‘Retinoblastoma’’ CancerNet. <http://cancernet.nci.nih
.gov/Cancer_Types/Retinoblastoma.shtml>.
Solutions by Sequence. June 20, 2001. <http://
www.solutionsbysequence.com>.

Lisa Andres, MS, CGC
Rebecca J. Frey, PhD

Retinol deficiency see Vitamin A deficiency

Retinopathies
Definition
Retinopathy is a noninflammatory disease of the
retina. There are many causes and types of
retinopathy.

Description
of

The retina is the thin membrane that lines the back
the eye and contains light-sensitive cells

3222

(photoreceptors). Light enters the eye and is focused
onto the retina. The photoreceptors send a message to
the brain via the optic nerve. The brain then ‘‘interprets’’ the electrical message sent to it, resulting in
vision. The macula is a specific area of the retina
responsible for central vision. The fovea is about 1.5
mm in size and located in the macula. The fovea is
responsible for sharp vision. When looking at something, the fovea should be directed at the object.
Retinopathy, or damage to the retina, has various
causes. A hardening or thickening of the retinal arteries
is called arteriosclerotic retinopathy. High blood pressure in the arteries of the body can damage the retinal
arteries and is called hypertensive retinopathy. The
spreading of a syphilis infection to the retinal blood
vessels cases syphilitic retinopathy, and diabetes
damages the retinal vessels resulting in a condition
called diabetic retinopathy. Sickle cell anemia also
affects the blood vessels in the eyes. Exposure to the
sun (or looking at the sun during an eclipse) can cause
damage (solar retinopathy), as well as certain drugs (for
example, chloroquine, thioridazine, and large doses of
tamoxifen). The arteries and veins can become blocked,
thus resulting in a retinal artery or vein occlusion. These
are just some of the causes of the various retinopathies.
Retinopathies are divided into two broad categories, simple or nonproliferative retinopathies and
proliferative retinopathies. The simple retinopathies
include the defects identified by bulging of the vessel
walls, by bleeding into the eye, by small clumps of
dead retinal cells called cotton wool exudates, and by
closed vessels. This form of retinopathy is considered
mild. The proliferative, or severe, forms of retinopathies include the defects identified by newly grown
blood vessels, by scar tissue formed within the eye,
by closed-off blood vessels that are badly damaged,
and by the retina breaking away from the mesh of
blood vessels that nourish it (retinal detachment).
While each disease has its own specific effect on
the retina, a general scenario for many of the retinopathies is as follows (note: not all retinopathies necessarily affect the blood vessels). Blood flow to the retina
is disrupted, either by blockage or breakdown of the
various vessels. This can lead to bleeding (hemorrhage) and fluids, cells, and proteins leaking into the
area (exudates). There can be a lack of oxygen to
surrounding tissues (hypoxia) or decreased blood
flow (ischemia). Chemicals produced by the body
then can cause new blood vessels to grow (neovascularization), however, these new vessels generally leak
and cause more problems. Neovascularization even
can grow on the colored part of the eye (iris). The
retina can swell and vision will be affected.
GALE ENCYCLOPEDIA OF MEDICINE

Retinopathies

Diabetic retinopathy is the leading cause of blindness in people ages 20 to 74. Diabetic retinopathy will
occur in 90% of persons with type 1 diabetes (insulindependent, or insulin requiring) and 65% of persons
with type II diabetes (non-insulin-dependent, or not
requiring insulin) by about 10 years after the beginning of diabetes. In the United States, new cases of
blindness most often are caused by diabetic retinopathy. Among these new cases of blindness, 12% are
people between the ages of 20 to 44 years, and 19%
are people between the ages of 45 to 64 years.

Causes and symptoms
There are many causes of retinopathy. Some of
the more common ones are listed below.
Diabetic retinopathy
Diabetes is a complex disorder characterized by
an inability of the body to properly regulate the levels
of sugar and insulin (a hormone made by the pancreas) in the blood. As diabetes progresses, the blood
vessels that feed the retina become damaged in different ways. The damaged vessels can have bulges in
their walls (aneurysms); they can leak blood into the
surrounding jelly-like material (vitreous) that fills the
inside of the eyeball; they can become completely
closed; or new vessels can begin to grow where there
would not normally be blood vessels. However,
although these new blood vessels are growing in the
eye, they cannot nourish the retina and they bleed
easily, releasing blood into the inner region of the
eyeball, which can cause dark spots and cloudy
vision.
Diabetic retinopathy begins prior to any outward
signs of disease being noticed. Once symptoms are
noticed, they include poorer than normal vision, fluctuating or distorted vision, cloudy vision, dark spots,
episodes of temporary blindness, or permanent
blindness.
Hypertensive retinopathy
High blood pressure can affect the vessels in the
eyes. Some blood vessels can narrow. The blood vessels can thicken and harden (arteriosclerosis). There
will be flame-shaped hemorrhages and macular swelling (edema). This edema may cause distorted or
decreased vision.
Sickle cell retinopathy
Sickle cell anemia occurs mostly in blacks and is a
hereditary disease that affects the red blood cells. The
GALE ENCYCLOPEDIA OF MEDICINE

A slit lamp view of a human eye with diabetic retinopathy.
(Custom Medical Stock Photo. Reproduced by permission.)

sickle-shaped blood cell reduces blood flow. People
will not have visual symptoms early in the disease.
However, patients need to be followed closely in case
neovascularization occurs.
Retinal vein and artery occlusion
Retinal vein occlusion generally occurs in the
elderly. There is usually a history of other systemic
disease, such as diabetes or high blood pressure.
The central retinal vein (CRV), or the retinal
veins branching off of the CRV, can become compressed, thus stopping the drainage of blood from
the retina. This may occur if the central retinal
artery hardens.
Symptoms of retinal vein occlusion include a sudden, painless loss of vision or field of vision in one eye.
There may be a sudden onset of floating spots (floaters) or flashing lights. Vision may be unchanged or
decrease dramatically.
Retinal artery occlusion generally is the result of an
embolism that dislodges from somewhere else in the
body and travels to the eye. Transient loss of vision
may precede an occlusion. Symptoms of a central
retinal artery or branch occlusion include a sudden,
painless loss of vision or decrease in visual field. Ten
percent of the cases of a retinal artery occlusion occur
because of giant cell arteritis (a chronic vascular
disease).
Solar retinopathy
Looking directly at the sun or watching an eclipse
can cause damage. There may be a loss of the central
visual field or decreased vision. The symptoms can
occur hours to days after the incident.
3223

Retinopathies

Fluorescein angiography, where a dye is injected
into the patient and the back of the eyes are viewed
and photographed, helps to locate leaky vessels.
Sometimes patients may become nauseated from
the dye.
A newer diagnostic method called digital retinal
photography can be used to screen those at high risk
for retinopathies, in particular, diabetics. Some
researchers say the technique could lead to more
cost-effective screening for people with diabetic
retinopathy.

A close-up view of a human eye following retinal hemorrhage.
(Custom Medical Stock Photo. Reproduced by permission.)

Drug-related retinopathies
Certain medications can affect different areas of
the retina. Doses of 20–40 mg a day of tamoxifen
usually do not cause a problem, but much higher
doses may cause irreversible damage.
Patients taking chloroquine for lupus, rheumatoid
arthritis, or other disorders may notice a decrease in
vision. If so, discontinuing medication will stop, but
not reverse, any damage. However, patients should
never discontinue medication without the advice of
their physician.
Patients taking thioridazine may notice a decrease
in vision or color vision.
These drug-related retinopathies generally only
affect patients taking large doses. However, patients
need to be aware if any medication they are taking will
affect the eyes. Patients should inform their doctors of
any visual effects.

Diagnosis
The damaged retinal blood vessels and other retinal changes are visible to an eye doctor when an
examination of the retina (fundus exam) is done.
This can be done using a hand-held instrument called
an ophthalmoscope or another instrument called a
binocular indirect ophthalmoscope. This allows the
doctor to see the back of the eye. Certain retinopathies
have classic signs (for example, vascular ‘‘sea fans’’ in
sickle cell, dot and blot hemorrhages in diabetes,
flame-shaped hemorrhages in high blood pressure).
Patients then may be referred for other tests to confirm
the underlying cause of the retinopathy. These tests
include blood tests and measurement of blood
pressure.
3224

Treatment
Retinal specialists are ophthalmologists who specialize in retinal disorders. Retinopathy is a disorder of
the retina that can result from different underlying
systemic causes, so general physicians should be consulted as well. For drug-related retinopathies, the
treatment generally is discontinuation of the drug
(only under the care of a physician).
Surgery with lasers can help to prevent blindness
or lessen any losses in vision. The high-energy light
from a laser is aimed at the weakened blood vessels in
the eye, destroying them. Scars will remain where the
laser treatment was performed. For that reason, laser
treatment cannot be performed everywhere. For
example, laser photocoagulation at the fovea would
destroy the area for sharp vision. Panretinal photocoagulation may be performed. This is a larger area of
treatment in the periphery of the retina; hopefully it
will decrease neovascularization. Prompt treatment of
proliferative retinopathy may reduce the risk of severe
vision loss by 50%.
Patients with retinal artery occlusion should be
referred to a cardiologist. Patients with retinal vein
occlusion need to be referred to a physician, as they
may have an underlying systemic disorder, such as
high blood pressure.

Prognosis
Nonproliferative retinopathy has a better prognosis than proliferative retinopathy. Prognosis
depends on the extent of the retinopathy, the cause,
and promptness of treatment.

Prevention
Complete eye examinations done regularly can
help detect early signs of retinopathy. Patients on
certain medications should have more frequent eye
exams. They also should have a baseline eye exam
GALE ENCYCLOPEDIA OF MEDICINE

Exudate—Cells, protein, fluid, or other material
that passes through blood vessel walls to accumulate in the surrounding tissue.
Neovascularization—New blood vessel formation–usually leaky vessels.
Nonproliferative retinopathy—Retinopathy without the growth of new blood vessels.
Proliferative retinopathy—Retinopathy with the
growth of new blood vessels (neovascularization).

when starting the drug. People with diabetes must take
extra care to have thorough, periodic eye exams, especially if early signs of visual impairment are noticed.
A 2003 report recommended re-screening eye exams
every two years for diabetics whose blood sugar had
remained in control, and more frequent exams if visual
symptoms appear. Anyone experiencing a sudden loss
of vision, decrease in vision or visual field, flashes of
light, or floating spots should contact their eye doctor
right away.

American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
Foundation Fighting Blindness. Executive Plaza I, Suite
800, 11350 McCormick Road, Hunt Valley, MD 210311014. (888) 394-3937. <http://www.blindness.org>.
Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://
www.preventblindness.org>.

Faye A. Fishman
Teresa G. Odle

Retrocaval ureter see Congenital ureter
anomalies

Retrograde cystography
Definition
A retrograde cystogram provides x-ray visualization of the bladder with injection of sterile dye.

Purpose

Proper medical treatment for any of the systemic
diseases known to cause retinal damage will help prevent retinopathy. For diabetics, maintaining proper
blood sugar and blood pressure levels is important as
well; however, some form of retinopathy usually will
occur in diabetics, given enough time. A proper diet,
particularly for those persons with diabetes, and stopping smoking also will help delay retinopathy.

A retrograde cystogram is performed to evaluate
the structure of the bladder and identify bladder disorders, such as tumors, or recurrent urinary tract infections. The presence of urine reflux (backward flow) into
the ureters may also be visualized with this x-ray study.

Frequent, thorough eye exams and control of systemic disorders are the best prevention.

The doctor should be made aware of any previous
history of reactions to shellfish, iodine, or any iodinecontaining foods or dyes. Allergic reactions during
previous dye studies is not necessarily a contraindication, as dye is not infused into the bloodstream for this
study. Other conditions to be considered by the physician prior to proceeding with the test include active
urinary tract infection, pregnancy, recent bladder surgery, or presence of obstruction that interferes with
passage of a urinary catheter.

Resources
PERIODICALS

Selby, Joe, Lynn Ackerson, and Talmadge Cooper. ‘‘Threeyear Incidence of Treatable Diabetic Eye Disease After
Negative Funduscopic Examination.’’ Diabetes June
2003: A60.
Usher, David, et al. ‘‘Automated Detection of Diabetic
Retinopathy in Digital Retinal Images.’’ Diabetes June
2003: A204.
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383. <http://
www.diabetes.org>.

GALE ENCYCLOPEDIA OF MEDICINE

Precautions

Description
After administration of anesthesia, the doctor will
insert a thin, tubelike instrument called a catheter
through the patient’s urethra and into the bladder.
The contrast medium is then injected through the
catheter into the bladder. X-ray pictures are taken at
various stages of filling, from various angles, to visualize the bladder. Additional films are taken after
3225

Retrograde cystography

KEY TERMS

Retrograde ureteropyelography

Normal results

KEY TERMS
Bladder—A balloon-like organ located in the lower
abdomen that stores urine.
Catheter—A thin tube used to inject or withdraw
fluids from the body.
Stones—Also known as calculi, stones result from
an excessive build-up of mineral crystals in the
kidney. Symptoms of stones include intense pain
in the lower back or abdomen, urinary tract infection, fever, burning sensation on urination, and/or
blood in the urine.
Ureter—Tube that carries urine from the kidney to
the bladder.
Urethra—Tube that empties urine from the bladder
to outside the body.

drainage of the dye. The procedure takes approximately one to one and one-half hours and the patient
may be asked to wait while films are developed.

A normal result would reveal no anatomical or
functional abnormalities.

Abnormal results
Abnormal results may indicate:


stones



blood clots



tumors



reflex (urine passing backward from the bladder into
the ureters)

Resources
ORGANIZATIONS

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.

Kathleen D. Wright, RN

Alternately, instead of a contrast dye and x-ray
pictures, the test can be done with a radioactive tracer
and a different camera. This is known as a ‘‘radionuclide’’ retrograde cystogram.

Preparation
The patient will be required to sign a consent form
after the risks and benefits of the procedure have been
explained. Laxatives or enemas may be necessary
before the procedure, as the bowel must be relatively
empty of stool and gas to provide visualization of the
urinary tract. Immediately before the procedure, the
patient should remove all clothing and jewelry, and
put on a surgical gown.

Aftercare
Sometimes, pulse, blood pressure, breathing status, and temperature are checked at regular intervals
after the procedure, until they are stable. The patient
may have some burning on urination for a few hours
after the test, due to the irritation of the urethra from
the catheter. The discomfort can be reduced by liberal
fluid intake, in order to dilute the urine. The appearance and amount of urine output should be noted, and
the doctor should be notified if blood appears in the
urine after three urinations. Also, patients should
report any signs of urinary infection, including chills,
fever, rapid pulse, and rapid breathing rate.
3226

Retrograde
ureteropyelography
Definition
A retrograde ureteropyelogram provides x-ray
visualization of the bladder, ureters, and the kidney
(renal) pelvis by injection of sterile dye into the renal
collecting system.

Purpose
A retrograde ureteropyelogram is performed to
determine the exact location of a ureteral obstruction
when it cannot be visualized on an intravenous pyelogram (a dye is injected and an x ray taken of the
kidneys and the tubes that carry urine to the bladder).
This may occur due to poor renal function and inadequate excretion of the contrast medium (dye).

Precautions
The doctor should be made aware of any previous
history of reactions to shellfish, iodine, or any iodinecontaining foods or dyes. Allergic reactions during
previous dye studies is not necessarily a
GALE ENCYCLOPEDIA OF MEDICINE



strictures



tumors

Resources
ORGANIZATIONS

Description
After administration of anesthesia, the doctor will
insert a thin, tubelike instrument (catheter) through
the patient’s urethra and into the bladder. A catheter is
then placed into the affected ureter to instill the contrast medium. X-ray pictures are taken to visualize the
ureter. If complete obstruction is found, a ureteral
catheter may be left in place and secured to an indwelling urethral catheter to facilitate drainage of urine.
The procedure takes approximately one hour.

Preparation
Laxatives or enemas may be necessary before the
procedure, as the bowel must be relatively empty to
provide visualization of the urinary tract. When general anesthesia is used for insertion of the ureteral
catheter, there should be no eating and drinking after
midnight prior to the procedure.

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.

Kathleen D. Wright, RN

Retrograde urethrography
Definition
Retrograde urethrography involves the use of
x-ray pictures to provide visualization of structural
problems or injuries to the urethra.

Purpose
Aftercare
Even if no catheters are left in place after the
procedure, the patient may have some burning on
urination for a few hours after the procedure due to
the irritation of the urethra. The discomfort can be
reduced by liberal fluid intake, in order to dilute the
urine. The appearance and amount of urine output
should be noted for 24 hours after the procedure. If a
stone was found, all urine should be strained to allow
chemical analysis of any stones passed spontaneously.
This will allow the doctor to provide advise on measures to prevent recurrent stone formation. Antibiotics
are usually given after the procedure to prevent urinary tract infection.

Normal results
A normal result would reveal no anatomical or
functional abnormalities.

Retrograde urethrography is used, in combination with a doctor’s observation and other tests, to
establish a diagnosis for individuals, almost exclusively men, who may have structural problems of the
urethra.

Precautions
The doctor should be made aware of any previous
history of reactions to shellfish, iodine, or any iodinecontaining foods or dyes. An earlier allergic reaction
during a dye study is not necessarily something that
makes the test inadvisable (a contraindication) as no
dye is injected into the bloodstream for this study.
Other conditions that should be considered by the
physician before the test is done include pregnancy,
recent urethral surgery, or severe inflammation of the
urethra, bladder, or prostate.

Description
Abnormal results
Abnormal results may indicate:


congenital abnormalities



fistulas or false passages



renal stones

GALE ENCYCLOPEDIA OF MEDICINE

The urethra is first visually examined by the doctor, and the opening is cleansed with an antiseptic
solution. A flexible rubber or plastic catheter is then
inserted into the urethra, and dye is injected into the
catheter. A clamp is applied to hold the dye in place
while x-ray pictures are taken of the urethral structure.
The clamp and catheter are then removed. The
3227

Retrograde urethrography

contraindication, as dye is not infused into the bloodstream for this study. Other conditions to be considered by the physician prior to proceeding with the test
include pregnancy and active urinary tract infection.

Reye’s syndrome

Resources

KEY TERMS
Bladder—The balloonlike organ in the lower abdomen that holds urine.
Catheter—Tube used to inject into or withdraw
fluids from the bladder.
Renal—Relating to the kidneys, from the Latin word
for kidneys, renes.
Urethra—Tube that carries the urine from the bladder out of the body.
Visualization—The process of making an internal
organ visible. A radiopaque subtance is introduced
into the body, then an x-ray picture of the desired
organ is taken.

procedure takes approximately 15 minutes. However,
the patient may be asked to wait while films are developed, which also permits the patient to be observed for
any immediate side effects from the dye. The test may
be performed in a hospital, doctor’s office, outpatient
center, or freestanding surgical facility. The time
involved for reporting of test results to the doctor
may vary from a few minutes to a few days.

Preparation
The patient will be asked to sign a consent form
after the risks and benefits of the procedure have been
explained. No diet or activity changes are necessary in
preparation for the procedure. The patient will be
asked to remove all clothing and put on a surgical
gown before the test begins.

Normal results
The presence of no anatomical or functional
abnormalities is considered a normal result.

Abnormal results
Abnormal findings may indicate:


congenital abormalities



fistulas or false passages



lacerations



strictures



valves, known as ‘‘posterior urethral valves’’



tumors

3228

ORGANIZATIONS

American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.
National Kidney Foundation. 30 East 33rd St., New York,
NY 10016. (800) 622-9010. <http://www.kidney.org>.

Kathleen D. Wright, RN

Retrograde urography see Retrograde
urethrography
Retropharyngeal abscess see Abscess

Reye’s syndrome
Definition
Reye’s syndrome is a disorder principally affecting the liver and brain, marked by rapid development
of life-threatening neurological symptoms.

Description
Reye’s syndrome is an emergency illness chiefly
affecting children and teenagers. It almost always follows a viral illness such as a cold, the flu, or chicken
pox. Reye’s syndrome may affect all the organs of the
body, but most seriously affects the brain and liver.
Rapid development of severe neurological symptoms,
including lethargy, confusion, seizures, and coma,
make Reye’s syndrome a life-threatening emergency.
Reye’s syndrome is a rare illness, even rarer now
than when first described in the early 1970s. The incidence of the disorder peaked in 1980, with 555 cases
reported. The number of cases declined rapidly thereafter due to decreased use of aspirin compounds for
childhood fever, an important risk factor for Reye’s
syndrome development. Because of its rarity, it is often
misdiagnosed as encephalitis, meningitis, diabetes, or
poisoning, and the true incidence may be higher than
the number of reported cases indicates.

Causes and symptoms
Reye’s syndrome causes fatty accumulation in the
organs of the body, especially the liver. In the brain, it
causes fluid accumulation (edema), which leads to a
rise in intracranial pressure. This pressure squeezes
blood vessels, preventing blood from entering the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

Although the cause remains unknown, Reye’s
syndrome appears to be linked to an abnormality in
the energy-converting structures (mitochondria)
within the body’s cells.

Acetylsalicylic acid—Aspirin; an analgesic, antipyretic, and antirheumatic drug prescribed to
reduce fever and for relief of pain and
inflammation.
Edema—The abnormal accumulation of fluid in
interstitial spaces of tissue.

Reye’s syndrome usually occurs after a viral,
fever-causing illness, most often an upper respiratory tract infection. Its cause is unknown. It is
most often associated with use of aspirin during
the fever, and for this reason aspirin and aspirincontaining products are not recommended for people under the age of 19 during fever. Reye’s
syndrome may occur without aspirin use, and in
adults, although very rarely.
After the beginning of recovery from the viral
illness, the affected person suddenly becomes worse,
with the development of persistent vomiting. This may
be followed rapidly by quietness, lethargy, agitation or
combativeness, seizures, and coma. In infants, diarrhea may be more common than vomiting. Fever is
usually absent at this point.

Diagnosis
Reye’s syndrome may be suspected in a child who
begins vomiting three to six days after a viral illness,
followed by an alteration in consciousness. Diagnosis
involves blood tests to determine the levels of certain
liver enzymes, which are highly elevated in Reye’s
syndrome. Other blood changes may occur as well,
including an increase in the level of ammonia and
amino acids, a drop in blood sugar, and an increase
in clotting time. A liver biopsy may also be done after
clotting abnormalities are corrected with vitamin K or
blood products. A lumbar puncture (spinal tap) may
be needed to rule out other possible causes, including
meningitis or encephalitis.

Treatment
Reye’s syndrome is a life-threatening emergency
that requires intensive management. The likelihood of
recovery is greatest if it is recognized early and treated
promptly. Children with Reye’s syndrome should be
managed in an intensive-care unit.
Treatment in the early stages includes intravenous sugar to return levels to normal and plasma
transfusion to restore normal clotting time.
Intracranial pressure is monitored, and if elevated,
is treated with intravenous mannitol and hyperventilation to constrict the blood vessels in the brain.
GALE ENCYCLOPEDIA OF MEDICINE

Mitochondria—Small rodlike, threadlike, or granular organelle witin the cytoplasm that function in
metabolism and respiration.

If the pressure remains high, barbiturates may be
used.

Prognosis
The mortality rate for Reye’s syndrome is between
30–50%. The likelihood of recovery is increased to
90% by early diagnosis and treatment. Almost all
children who survive Reye’s syndrome recover fully,
although recovery may be slow. In some patients,
permanent neurologic damage may remain, requiring
physical or educational special services and
equipment.

Prevention
Because Reye’s syndrome is so highly correlated
with use of aspirin for fever in young people, avoidance of aspirin use by children is strongly recommended. Aspirin is in many over-the-counter and
prescription drugs, including drugs for headache,
fever, menstrual cramps, muscle pain, nausea, upset
stomach, and arthritis. It may be used in drugs taken
orally or by suppository.
Any of the following ingredients indicates that
aspirin is present:


aspirin



acetylsalicylate



acetylsalicylic acid



salicylic acid



salicylate

Teenagers who take their own medications without parental consultation should be warned not to
take aspirin-containing drugs.
3229

Reye’s syndrome

brain. Untreated, this pressure increase leads to brain
damage and death.

Rheumatic fever

Resources
ORGANIZATIONS

National Reye’s Syndrome Foundation. P.O. Box 829,
Bryan, OH 43506-0829. (800) 233-7393. <http://
www.bright.net/~reyessyn>.

Richard Robinson

Rh disease see Erythroblastosis fetalis
Rh incompatibility see Erythroblastosis
fetalis
Rh typing see Blood typing and
crossmatching

Rheumatic fever
Definition
Rheumatic fever (RF) is an illness which arises as
a complication of untreated or inadequately treated
strep throat infection. Rheumatic fever can seriously
damage the valves of the heart.

Description
Throat infection with a member of the Group A
streptococcus (strep) bacteria is a common problem
among school-aged children. It is easily treated with a
ten-day course of antibiotics by mouth. However,
when such a throat infection occurs without symptoms, or when a course of medication is not taken
for the full ten days, there is a 3% chance of that
person developing rheumatic fever. Other types of
strep infections (such as of the skin) do not put the
patient at risk for RF.
Children between the ages of five and fifteen are
most susceptible to strep throat, and therefore most
susceptible to rheumatic fever. Other risk factors
include poverty, overcrowding (as in military camps),
and lack of access to good medical care. Just as strep
throat occurs most frequently in fall, winter, and early
spring, so does rheumatic fever.

Causes and symptoms
Two different theories exist as to how a bacterial
throat infection can develop into the disease called
rheumatic fever. One theory, less supported by
research evidence, suggests that the bacteria produce
3230

some kind of poisonous chemical (toxin). This toxin is
sent into circulation throughout the bloodstream, thus
affecting other systems of the body.
Research seems to point to a different theory,
however. This theory suggests that the disease is
caused by the body’s immune system acting inappropriately. The body produces immune cells (called antibodies), which are specifically designed to recognize
and destroy invading agents; in this case, streptococcal
bacteria. The antibodies are able to recognize the bacteria because the bacteria contain special markers
called antigens. Due to a resemblance between
Group A streptococcus bacteria’s antigens and antigens present on the body’s own cells, the antibodies
mistakenly attack the body itself.
It is interesting to note that members of certain
families seem to have a greater tendency to develop
rheumatic fever than do others. This could be related
to the above theory, in that these families may have
cell antigens which more closely resemble streptococcal antigens than do members of other families.
In addition to fever, in about 75% of all cases of
RF one of the first symptoms is arthritis. The joints
(especially those of the ankles, knees, elbows, and
wrists) become red, hot, swollen, shiny, and extraordinarily painful. Unlike many other forms of arthritis,
the arthritis may not occur symmetrically (affecting a
particular joint on both the right and left sides, simultaneously). The arthritis of RF rarely strikes the fingers, toes, or spine. The joints become so tender that
even the touch of bedsheets or clothing is terribly
painful.
A peculiar type of involuntary movement,
coupled with emotional instability, occurs in about
10% of all RF patients (the figure used to be about
50%). The patient begins experiencing a change in
coordination, often first noted by changes in handwriting. The arms or legs may flail or jerk uncontrollably. The patient seems to develop a low threshold for
anger and sadness. This feature of RF is called
Sydenham’s chorea or St. Vitus’ Dance.
A number of skin changes are common to RF.
A rash called erythema marginatum develops (especially in those patients who will develop heart problems from their illness), composed of pink
splotches, which may eventually spread into each
other. It does not itch. Bumps the size of peas may
occur under the skin. These are called subcutaneous
nodules; they are hard to the touch, but not painful.
These nodules most commonly occur over the knee
and elbow joint, as well as over the spine.
GALE ENCYCLOPEDIA OF MEDICINE

The major criteria include:


carditis



arthritis



chorea



subcutaneous nodules



erythema marginatum
The minor criteria include:

A magnified image of cardiac muscle damaged by chronic
myocarditis caused by rheumatic fever. (Science Photo Library.
Custom Medical Stock Photo. Reproduced by permission.)

The most serious problem occurring in RF is called
pancarditis (‘‘pan’’ means total; ‘‘carditis’’ refers to
inflammation of the heart). Pancarditis is an inflammation that affects all aspects of the heart, including the
lining of the heart (endocardium), the sac containing
the heart (pericardium), and the heart muscle itself
(myocardium). About 40-80% of all RF patients
develop pancarditis. This RF complication has the
most serious, long-term effects. The valves within the
heart (structures which allow the blood to flow only in
the correct direction, and only at the correct time in the
heart’s pumping cycle) are frequently damaged during
the course of pancarditis. This may result in blood
which either leaks back in the wrong direction, or has
a difficult time passing a stiff, poorly moving valve.
Either way, damage to a valve can result in the heart
having to work very hard in order to move the blood
properly. The heart may not be able to ‘‘work around’’
the damaged valve, which may result in a consistently
inadequate amount of blood entering the circulation.

Diagnosis
Diagnosis of RF is done by carefully examining
the patient. A list of diagnostic criteria has been
GALE ENCYCLOPEDIA OF MEDICINE



fever



joint pain (without actual arthritis)



evidence of electrical changes in the heart (determined by measuring electrical characteristics of the
heart’s functioning during a test called an electrocardiogram, or EKG)



evidence (through a blood test) of the presence in the
blood of certain proteins, which are produced early
in an inflammatory/infectious disease.

Tests are also performed to provide evidence of
recent infection with group A streptococcal bacteria.
A swab of the throat can be taken, and smeared on a
substance in a petri dish, to see if bacteria will multiply
and grow over 24-72 hours. These bacteria can then be
specially processed, and examined under a microscope, to identify streptococcal bacteria. Other tests
can be performed to see if the patient is producing
specific antibodies; that are only made in response to
a recent strep infection.

Treatment
A 10-day course of penicillin by mouth, or a single
injection of penicillin G-is the first line of treatment for
RF. Patients will need to remain on some regular dose
of penicillin to prevent recurrence of RF. This can
mean a small daily dose of penicillin by mouth, or an
injection every three weeks. Some practitioners keep
patients on this regimen for five years, or until they
reach 18 years of age (whichever comes first). Other
practitioners prefer to continue treating those patients
who will be regularly exposed to streptococcal bacteria
(teachers, medical workers), as well as those patients
with known RF heart disease.
Arthritis quickly improves when the patient is given
a preparation containing aspirin, or some other anti3231

Rheumatic fever

created. These ‘‘Jones Criteria’’ are divided into
major and minor criteria. A patient can be diagnosed
with RF if he or she has either two major criteria
(conditions), or one major and two minor criteria. In
either case, it must also be proved that the individual
has had a previous infection with streptococcus.

Rheumatoid arthritis

KEY TERMS
Antibodies—Specialized cells of the immune system which can recognize organisms that invade the
body (such as bacteria, viruses, and fungi). The
antibodies are then able to set off a complex chain
of events designed to kill these foreign invaders.
Antigen—A special, identifying marker on the outside of cells.
Arthritis—Inflammation of the joints.
Autoimmune disorder—A disorder in which the
body’s antibodies mistake the body’s own tissues
for foreign invaders. The immune system therefore
attacks and causes damage to these tissues.
Chorea—Involuntary movements in which the
arms or legs may jerk or flail uncontrollably.
Immune system—The system of specialized
organs, lymph nodes, and blood cells throughout
the body, which work together to prevent foreign
invaders (bacteria, viruses, fungi, etc.) from taking
hold and growing.
Inflammation—The body’s response to tissue
damage. Includes hotness, swelling, redness, and
pain in the affected part.
Pancarditis—Inflammation of the lining of the heart,
the sac around the heart, and the muscle of the heart.

inflammatory agent (ibuprofen). Mild carditis will also
improve with such anti-inflammatory agents, although
more severe cases of carditis will require steroid medications. A number of medications are available to treat the
involuntary movements of chorea, including diazepam
for mild cases, and haloperidol for more severe cases.

Prognosis
The long-term prognosis of an RF patient
depends primarily on whether he or she develops carditis. This is the only manifestation of RF which can
have permanent effects. Those patients with no or
mild carditis have an excellent prognosis. Those with
more severe carditis have a risk of heart failure, as well
as a risk of future heart problems, which may lead to
the need for valve replacement surgery.

Prevention
Prevention of the development of RF involves
proper diagnosis of initial strep throat infections,
3232

and adequate treatment within 10 days with an appropriate antibiotic. Prevention of RF recurrence requires
continued antibiotic treatment, perhaps for life.
Prevention of complications of already-existing RF
heart disease requires that the patient always take a
special course of antibiotics when he or she undergoes
any kind of procedure (even dental cleanings) that
might allow bacteria to gain access to the
bloodstream.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Rheumatoid arthritis
Definition
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and deformity
of the joints. Other problems throughout the body
(systemic problems) may also develop, including
inflammation of blood vessels (vasculitis), the development of bumps (called rheumatoid nodules) in various parts of the body, lung disease, blood disorders,
and weakening of the bones (osteoporosis).

Description
The skeletal system of the body is made up of
different types of strong, fibrous tissue called connective tissue. Bone, cartilage, ligaments, and tendons are
all forms of connective tissue that have different compositions and different characteristics.
The joints are structures that hold two or more
bones together. Some joints (synovial joints) allow for
movement between the bones being joined (articulating bones). The simplest synovial joint involves two
bones, separated by a slight gap called the joint cavity.
The ends of each articular bone are covered by a layer
of cartilage. Both articular bones and the joint cavity
are surrounded by a tough tissue called the articular
capsule. The articular capsule has two components,
the fibrous membrane on the outside and the synovial
membrane (or synovium) on the inside. The fibrous
membrane may include tough bands of tissue called
ligaments, which are responsible for providing
GALE ENCYCLOPEDIA OF MEDICINE

for perhaps an hour. Over time, the joints become
deformed. The joints may be difficult to straighten,
and affected fingers and toes may be permanently bent
(flexed). The hands and feet may curve outward in an
abnormal way.

In rheumatoid arthritis (RA), the synovial membrane becomes severely inflamed. Usually thin and
delicate, the synovium becomes thick and stiff, with
numerous infoldings on its surface. The membrane is
invaded by white blood cells, which produce a variety
of destructive chemicals. The cartilage along the
articular surfaces of the bones may be attacked and
destroyed, and the bone, articular capsule, and ligaments may begin to wear away (erode). These processes severely interfere with movement in the joint.

Many patients also notice increased fatigue, loss
of appetite, weight loss, and sometimes fever.
Rheumatoid nodules are bumps that appear under
the skin around the joints and on the top of the arms
and legs. These nodules can also occur in the tissue
covering the outside of the lungs and lining the chest
cavity (pleura), and in the tissue covering the brain and
spinal cord (meninges). Lung involvement may cause
shortness of breath and is seen more in men. Vasculitis
(inflammation of the blood vessels) may interfere with
blood circulation. This can result in irritated pits
(ulcers) in the skin, tissue death (gangrene), and interference with nerve functioning that causes numbness
and tingling.

RA exists all over the world and affects men and
women of all races. In the United States alone, about
two million people suffer from the disease. Women are
three times more likely than men to have RA. About
80% of people with RA are diagnosed between the
ages of 35-50. RA appears to run in families, although
certain factors in the environment may also influence
the development of the disease.

Causes and symptoms
The underlying event that promotes RA in a person is unknown. Given the known genetic factors
involved in RA, some researchers have suggested
that an outside event occurs that triggers the disease
cycle in a person with a particular genetic makeup.
Many researchers are examining the possibility
that exposure to an organism (like a bacteria or
virus) may be the first event in the development of
RA. The body’s normal response to such an organism
is to produce cells that can attack and kill the organism, protecting the body from the foreign invader. In
an autoimmune disease like RA, this immune cycle
spins out of control. The body produces misdirected
immune cells, which accidentally identify parts of the
person’s body as foreign. These immune cells then
produce a variety of chemicals that injure and destroy
parts of the body.
RA can begin very gradually, or it can strike
quickly. The first symptoms are pain, swelling, and
stiffness in the joints. The most commonly involved
joints include hands, feet, wrists, elbows, and ankles,
although other joints may also be involved. The joints
are affected in a symmetrical fashion. This means that
if the right wrist is involved, the left wrist is also
involved. Patients frequently experience painful joint
stiffness when they first get up in the morning, lasting
GALE ENCYCLOPEDIA OF MEDICINE

Juvenile RA is a chronic inflammatory disease
that affects the joints of children less than 16 years
old. It is estimated to affect as many as 250,000 children in the United States alone. Most children with
juvenile RA have arthritis when the illness starts,
which affects multiple joints in 50% of these children,
and only one joint in 30%. In all, 20% of the children
affected by juvenile RA have the acute systemic form
of the disease, which is characterized by fever, joint
inflammation, rash, liver disease, and gastrointestinal
disease.
Two periods of childhood are associated with an
increased incidence of onset of juvenile RA. The first is
from one to three years of age, and the second, from
eight to 12 years. When more than four joints are
affected, the disease is described as being polyarticular. If less than four joints are affected, the disease is
known as pauciarticular. juvenile RA and this particular manifestation falls into two categories. The first
occurs in girls aged one to four years old, and the onset
of joint involvement is in the knees, ankles, or elbows.
The second form occurs in boys aged eight years and
older, and involves the larger joints, such as those of
the hips and legs.

Diagnosis
There are no tests available that can absolutely
diagnose RA. Instead, a number of tests exist that can
suggest the diagnosis of RA. Blood tests include a
special test of red blood cells (called erythrocyte sedimentation rate), which is positive in nearly 100% of
patients with RA. However, this test is also positive in
a variety of other diseases. Tests for anemia are usually
3233

Rheumatoid arthritis

support to the joints. The synovial membrane has
special cells and many tiny blood vessels (capillaries).
This membrane produces a supply of synovial fluid
that fills the joint cavity, lubricates it, and helps the
articular bones move smoothly about the joint.

Rheumatoid arthritis

positive in patients with RA, but can also be positive in
many other unrelated diseases. Rheumatoid factor is
another diagnostic test that measures the presence and
amounts of rheumatoid factor in the blood.
Rheumatoid factor is an autoantibody found in
about 80% of patients with RA. It is often not very
specific however, because it is found in about 5% of all
healthy people and in 10-20% of healthy people over
the age of 65. In addition, rheumatoid factor is also
positive in a large number of other autoimmune diseases and other infectious diseases, including systemic
lupus erythematosus, bacterial endocarditis, malaria,
and syphilis. In addition, young people who have a
process called juvenile rheumatoid arthritis often have
no rheumatoid factor present in their blood.
Finally, the clinician may examine the synovial
fluid, by inserting a thin needle into a synovial joint.
In RA, this fluid has certain characteristics that indicate active inflammation. The fluid is cloudy, with
increased protein and decreased or normal glucose. It
also contains a higher than normal number of white
blood cells. While these findings suggest inflammatory
arthritis, they are not specific to RA.

Treatment
There is no cure available for RA. However, treatment is available to combat the inflammation in order
to prevent destruction of the joints, and to prevent
other complications of the disease. Efforts are also
made to maintain flexibility and mobility of the joints.
The ‘‘first line’’ agents for the treatment of RA
include nonsteroidal anti- inflammatory agents
(NSAIDs) and aspirin, which are used to decrease
inflammation and to treat pain. The NSAIDs include
naproxen (Naprosyn), ibuprofen (Advil, Medipren,
Motrin), and etodolac (Lodine). While these medications can be helpful, they do not interrupt the progress
of the disease. Low-dose steroid medications can be
helpful at both managing symptoms and slowing the
progress of RA. Disease-modifying antirheumatic
drugs, including gold compounds, D-penicillamine,
certain antimalarial-like drugs, and sulfasalazine
(Azulfadine) are also often the first agents clinicians
use to treat RA, but in patients with the aggressive
destructive type of RA, more slow-acting medications
are needed. Methotrexate, azathioprine, and cyclophosphamide are all drugs that suppress the immune
system and can decrease inflammation. All of the
drugs listed have significant toxic side effects, which
require healthcare professionals to carefully compare
the risks associated with these medications versus the
benefits.
3234

Recently, several categories of drugs have been
explored and developed for the treatment of RA. The
first is a category of agents known as biological
response modifiers. These work to reduce joint inflammation by blocking a substance called tumor necrosis
factor (TNF). TNF is a protein that triggers inflammation during the body’s normal immune responses.
When TNF production is not regulated, the excess
TNF can cause inflammation. Three agents in this
class have become ‘‘second line’’ drugs for the treatment of RA. These are etanercept (Enbrel), leflunamide (Arava), and infliximab (Remicade), and they
are recommended for patients in whom other medications have not been effective. Etanercept is approved
by the FDA but is not recommended for patients with
active infection. It is given twice weekly via subcutaneous injections by either the patient or a health care
professional. Because this agent is so new, long-term
side effects have not been fully studied. Infliximab is
given intravenously once every eight weeks, and is
approved for combined use with methotrexate to combat RA.
The cyclo-oxygenase-2 (COX-2) inhibitors are
another category of drugs used to treat RA. Like the
traditional NSAIDs, the COX-2 inhibitors work to
block COX-2, which is an enzyme that stimulates
inflammatory responses in the body. Unlike the
NSAIDs, the COX-2 inhibitors do not carry a high
risk of gastrointestinal ulcers and bleeding, because
they do not inhibit COX-1, which is the enzyme that
protects the stomach lining. These new agents include
celecoxib (Celebrex) and rofecoxib (Vioxx). Celecoxib
has been approved by the FDA for the treatment of
RA and osteoarthritis, and is taken once or twice daily
by mouth. Rofecoxib is approved for RA and osteoarthritis, and for acute pain caused by primary dysmenorrhea and surgery.
Total bed rest is sometimes prescribed during the
very active, painful phases of RA. Splints may be used
to support and rest painful joints. Later, after inflammation has somewhat subsided, physical therapists
may provide a careful exercise regimen in an attempt
to maintain the maximum degree of flexibility and
mobility. Joint replacement surgery, particularly for
the knee and the hip joints, is sometimes recommended when these joints have been severely
damaged.

Alternative treatment
A variety of alternative therapies has been recommended for patients with RA. Meditation, hypnosis,
guided imagery, and relaxation techniques have been
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Articular bones—Two or more bones connected to
each other via a joint.
Joint—Structures holding two or more bones
together.

A multitude of nutritional supplements can be useful for RA. Fish oils, the enzymes bromelain and
pancreatin, and the antioxidants (vitamins A, C, and
E, selenium, and zinc) are the primary supplements to
consider.

Pauciarticular juvenile RA—Rheumatoid arthritis
found in children that affects less than four joints.
Polyarticular juvenile RA—Rheumatoid arthritis
found in children that affects more than four joints.

Many herbs also are useful in the treatment of
RA. Anti-inflammatory herbs may be very helpful,
including tumeric (Curcuma longa), ginger (Zingiber
officinale), feverfew (Chrysanthemum parthenium),
devil’s claw (Harpagophytum procumbens), Chinese
thoroughwax (Bupleuri falcatum), and licorice
(Glycyrrhiza glabra). Lobelia (Lobelia inflata) and
cramp bark (Vibernum opulus) can be applied topically
to the affected joints.

Synovial joint—A type of joint that allows articular
bones to move.
Synovial membrane—The membrane that lines the
inside of the articular capsule of a joint and produces a lubricating fluid called synovial fluid.

Homeopathic practitioners recommended Rhus
toxicondendron and Bryonia (Bryonia alba) for acute
prescriptions, but constitutional treatment, generally
used for chronic problems like RA, is more often
recommended. Yoga has been used for RA patients
to promote relaxation, relieve stress, and improve flexibility. Nutritionists suggest that a vegetarian diet low
in animal products and sugar may help to decrease
both inflammation and pain from RA. Beneficial
foods for patients with RA include cold water fish
(mackerel, herring, salmon, and sardines) and flavonoid-rich berries (cherries, blueberries, hawthorn berries, blackberries, etc.).



extremely high levels of rheumatoid factor.



consistent, lasting inflammation.



evidence of erosion of bone, joint, or cartilage on x
rays.



poverty.



older age at diagnosis.



rheumatoid nodules.



other coexisting diseases.



certain genetic characteristics, diagnosable through
testing.

RA, considered an autoimmune disorder, is often
connected with food allergies/intolerances. An elimination/challenge diet can help to decrease symptoms
of RA as well as identify the foods that should be
eliminated to prevent flare-ups and recurrences.
Hydrotherapy can help to greatly reduce pain and
inflammation. Moist heat is more effective than dry
heat, and cold packs are useful during acute flare-ups.

Patients with RA have a shorter life span, averaging a decrease of three to seven years of life. Patients
sometimes die when very severe disease, infection, and
gastrointestinal bleeding occur. Complications due to
the side effects of some of the more potent drugs used
to treat RA are also factors in these deaths.

Prognosis
About 15% of all RA patients will have symptoms
for a short period of time and will ultimately get better,
leaving them with no long-term problems. A number
of factors are considered to suggest the likelihood of a
worse prognosis. These include:


race and gender (female and Caucasian).



more than 20 joints involved.



extremely high erythrocyte sedimentation rate.

GALE ENCYCLOPEDIA OF MEDICINE

Prevention
There is no known way to prevent the development of RA. The most that can be hoped for is to
prevent or slow its progress.
Resources
BOOKS

Arthritis Foundation. The Good Living with Rheumatoid
Arthritis. New York: Longstreet Press Inc., 2000.
PERIODICALS

Case, J. P. ‘‘Old and New Drugs Used in Rheumatoid
Arthritis: A Historical Perspective. Part 2: The Newer
3235

Rheumatoid arthritis

used effectively to control pain. Acupressure and acupuncture have also been used for pain. Bodywork can
be soothing, decreasing stress and tension, and is
thought to improve/restore chemical balance within
the body.

Rhinitis

Drugs and Drug Strategies.’’ American Journal of
Therapeutics May-June 2001: 163-79.
Goekoop, Y. P., et al. ‘‘Combination Therapy in
Rheumatoid Arthritis.’’ Current Opinions in
Rheumatology May 2001: 177-83.
Koivuniemi, R., and M. Leirisalo-Repo. ‘‘Juvenile Chronic
Arthritis in Adult Life: A Study of Long-term Outcome
in Patients with Juvenile Chronic Arthritis or Adult
Rhuematoid Arthritis.’’ Clinical Rheumatology 1999:
220-6.

Liz Meszaros

Rheumatoid spondylit see Ankylosing
spondylitis

Rhinitis
Definition
Rhinitis is inflammation of the mucous lining of
the nose.

Description
Rhinitis is a nonspecific term that covers infections, allergies, and other disorders whose common
feature is the location of their symptoms. In rhinitis,
the mucous membranes become infected or irritated,
producing a discharge, congestion, and swelling of the
tissues. The most widespread form of infectious rhinitis is the common cold.
The common cold is the most frequent viral infection in the general population, causing more absenteeism from school or work than any other illness. Colds
are self-limited, lasting about 3-10 days, although they
are sometimes followed by a bacterial infection.
Children are more susceptible than adults; teenage
boys more susceptible than teenage girls; and adult
women more susceptible than adult men. In the
United States, colds are most frequent during the late
fall and winter.

Causes and symptoms
Colds can be caused by as many as 200 different
viruses. The viruses are transmitted by sneezing and
coughing, by contact with soiled tissues or handkerchiefs, or by close contact with an infected person. Colds
are easily spread in schools, offices, or any place where
people live or work in groups. The incubation period
ranges between 24 and 72 hours.
3236

The onset of a cold is usually sudden. The virus
causes the lining of the nose to become inflamed and
produce large quantities of thin, watery mucus.
Children sometimes run a fever with a cold. The
inflammation spreads from the nasal passages to the
throat and upper airway, producing a dry cough, headache, and watery eyes. Some people develop muscle or
joint aches and feel generally tired or weak. After
several days, the nose becomes less inflamed and the
watery discharge is replaced by a thick, sticky mucus.
This change in the appearance of the nasal discharge
helps to distinguish rhinitis caused by a viral infection
from rhinitis caused by an allergy.

Diagnosis
There is no specific test for viral rhinitis. The
diagnosis is based on the symptoms. In children, the
doctor will examine the child’s throat and glands to
rule out measles and other childhood illnesses that
have similar early symptoms. Adults whose symptoms last longer than a week may require further
testing to rule out a secondary bacterial infection,
or an allergy. Bacterial infections can usually be
identified from a laboratory culture of the patient’s
nasal discharge. Allergies can be evaluated by blood
tests, skin testing for specific substances, or nasal
smears.

Treatment
There is no cure for the common cold; treatment is
given for symptom relief. Medications include aspirin
or nonsteroidal anti-inflammatory drugs (NSAIDs) for
headache and muscle pain, and decongestants to
relieve stuffiness or runny nose. Patients should be
warned against overusing decongestants, because
they can cause a rebound effect. Over-the-counter
(OTC) antihistamines are also available; however,
most antihistamines carry warnings of drowsiness
and the inability to do some tasks while medicated.
Claritin is a prescription-strength OTC non-drowsy
antihistamine that helps relieve symptoms of rhinitis.
Antibiotics are not given for colds because they do not
kill viruses.
Supportive care includes bed rest and drinking
plenty of fluid.
Treatments under investigation include the use of
ultraviolet light and injections of interferon.
Many prescription and over-the-counter drugs
are available to help control the symptoms of allergic rhinitis. The most common class is
antihistamines.
GALE ENCYCLOPEDIA OF MEDICINE

Interferon—A protein produced by cells infected
by a virus that stimulates the body’s resistance to
the virus.

Alternative treatment
Homeopaths might prescribe any of 10 different remedies, depending on the appearance of the
nasal discharge, the patient’s emotional state, and
the stage of infection. Naturopaths would recommend vitamin A and zinc supplements, together
with botanical preparations made from goldenseal
(Hydrastis canadensis), licorice (Glycyrrhiza glabra), or astragalus (Astragalus membraneceus)
root.
At one time, the herb (Echinacea spp.) was touted as a remedy to relieve cold and rhinitis symptoms. However, a study published in 2004 reported
that the herb failed to relieve cold symptoms in 400
children taking it and caused skin rashes in some
children.

Prognosis

Rhinoplasty

KEY TERMS

Rhinoplasty
Definition
The term rhinoplasty means ‘‘nose molding’’ or
‘‘nose forming.’’ It refers to a procedure in plastic
surgery in which the structure of the nose is changed.
The change can be made by adding or removing bone
or cartilage, grafting tissue from another part of the
body, or implanting synthetic material to alter the
shape of the nose.
Rhinoplasty is the most frequently performed cosmetic surgical procedure in the United States as of the
early 2000s. According to the American Society of
Plastic Surgeons (ASPS), 356,554 rhinoplasties were
performed in the United States in 2003, compared to
254,140 breast augmentations and 128,667 facelifts.

Purpose
Rhinoplasty is most often performed for cosmetic
reasons. A nose that is too large, crooked, misshapen,
malformed at birth, or deformed by an injury or cancer surgery can be given a more pleasing appearance.
If breathing is impaired due to the form of the nose or
to an injury, it can often be improved with rhinoplasty.

Precautions

Most colds resolve completely in about a week.
Complications are unusual but may include sinusitis
(inflammation of the nasal sinuses), bacterial infections, or infections of the middle ear.

Prevention
There is no vaccine effective against colds, and
infection does not confer immunity. Prevention
depends on:


washing hands often, especially before touching the
face



minimizing contact with people already infected



not sharing hand towels, eating utensils, or water
glasses.

The best candidates for rhinoplasty are those with
relatively minor deformities. Nasal anatomy and proportions are quite varied and the final look of any
rhinoplasty operation is the result of the patient’s
anatomy, as well as of the surgeon’s skill.
The quality of the skin plays a major role in the
outcome of rhinoplasty. Patients with extremely thick
skin may not see a definite change in the underlying
bone structure after surgery. On the other hand, thin
skin provides almost no cushion to hide the most
minor of bone irregularities or imperfections.
A cosmetic change in the shape of the nose will
change a person’s appearance, but it will not change
self-image. A person who expects a different lifestyle
after rhinoplasty is likely to be disappointed.
Rhinoplasty should not be performed until the
pubertal growth spurt is complete, between ages
14-15 for girls and older for boys.

Resources
PERIODICALS

‘‘Study: Echinacea Is Ineffective.’’ Chain Drug Review
February 16, 2004: 25.

Rebecca J. Frey, PhD
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

The cost of rhinoplasty depends on the difficulty
of the work required and on the specialist chosen.
Prices run from about $3,000 to over $6,000. If the
problem was caused by an injury, insurance will
usually cover the cost. A rhinoplasty done only to
3237

Rhinoplasty

change a person’s appearance is not usually covered
by insurance.

Description
The external nose is composed of a series of interrelated parts which include the skin, the bony pyramid, cartilage, and the tip of the nose, which is both
cartilage and skin. The strip of skin separating the
nostrils is called the columella.
Surgical approaches to nasal reconstruction are
varied. Internal rhinoplasty involves making all incisions inside the nasal cavity. The external or ‘‘open’’
technique involves a skin incision across the base of
the nasal columella. An external incision allows the
surgeon to expose the bone and cartilage more fully
and is most often used for complicated procedures.
During surgery, the surgeon will separate the skin
from the bone and cartilage support. The framework
of the nose is then reshaped in the desired form. Shape
can be altered by removing bone, cartilage, or skin.
The remaining skin is then replaced over the new
framework. If the procedure requires adding to the
structure of the nose, the donated bone, cartilage, or
skin can come from the patient or from a synthetic
source.
When the operation is over, the surgeon will apply
a splint to help the bones maintain their new shape.
The nose may also be packed, or stuffed with a dressing, to help stabilize the septum.
When a local anesthetic is used, light sedation is
usually given first, after which the operative area is
numbed. It will remain insensitive to pain for the
length of the surgery. A general anesthetic is used for
lengthy or complex procedures or if the doctor and
patient agree that it is the best option.
Simple rhinoplasty is usually performed in an outpatient surgery center or in the surgeon’s office. Most
procedures take only an hour or two, and patients may
return home right away. Complex procedures may be
done in the hospital and require a short stay.

Preparation
During the initial consultation, the patient and
surgeon will determine what changes can be made in
the shape of the nose. Most doctors take photographs
at the same time. The surgeon will also explain the
techniques and anesthesia options available to the
patient.
For legal reasons, many plastic surgeons now
screen patients for psychological stability as well as
3238

general physical fitness for surgery. When a person
consults a plastic surgeon about a rhinoplasty, the
doctor will spend some time talking with the patient
about his or her motives for facial surgery. The following are considered psychological warning signs:


The patient is considering surgery to please someone
else, most often a spouse or partner.



The patient expects facial surgery to guarantee career
advancement.



The patient has a history of multiple cosmetic procedures and/or complaints about previous surgeons.



The patient thinks that the surgery will solve all his or
her life problems.



The patient has an unrealistic notion of what he or
she will look like after surgery.



The patient seems otherwise emotionally unstable.

The patient and surgeon should also discuss
guidelines for eating, drinking, smoking, taking or
avoiding certain medications, and washing of the face.

Aftercare
Patients usually feel fine immediately after surgery; however, most surgery centers do not allow
patients to drive themselves home after an operation.
The first day after surgery there will be some
swelling of the face. Patients should stay in bed with
their heads elevated for at least a day. The nose may
hurt and a headache is not uncommon. The surgeon
will prescribe medication to relieve these conditions.
Swelling and bruising around the eyes will increase for
a few days, but will begin to diminish after about the
third day. Slight bleeding and stuffiness are normal,
and vary according to the extensiveness of the surgery
performed. Most people are up in two days, and back
to school or work in a week. No strenuous activities
are allowed for two to three weeks.
Patients are given a list of postoperative instructions, which include requirements for hygiene, exercise, eating, and follow-up visits to the doctor. Patients
should not blow their noses for the first week to avoid
disruption of healing. It is extremely important to keep
the surgical dressing dry. Dressings, splints, and
stitches are removed in one to two weeks. Patients
should avoid sunburn.
Patients should remember that it may take as long
as a year for the nose to assume its final shape; the tip
of the nose in particular may be mildly swollen for
several months.
GALE ENCYCLOPEDIA OF MEDICINE

Alloplastic Implant Rejection.’’ Archives of Facial and
Plastic Surgery 6 (May-June 2004): 192–196.
ORGANIZATIONS

Cartilage—Firm supporting tissue that does not
contain blood vessels.
Columella—The strip of skin running from the tip of
the nose to the upper lip, which separates the
nostrils.
Septum—The dividing wall in the nose.

American Academy of Facial Plastic and Reconstructive
Surgery (AAFPRS). 310 South Henry Street,
Alexandria, VA 22314. (703) 299-9291. <http://
www.facemd.org>.
American Society of Plastic Surgeons (ASPS). 444 East
Algonquin Road, Arlington Heights, IL 60005. (847)
228-9900. <http://www.plasticsurgery.org>.
OTHER

Risks
Any type of surgery carries a degree of risk. There
is always the possibility of unexpected events, such as
an infection or a reaction to the anesthesia. Some
patients may have a so-called foreign body reaction
to a nasal implant made from synthetic materials. In
these cases the surgeon can replace the implant with a
piece of cartilage from the patient’s own body.
Some risks of rhinoplasty are social or psychological. The ASPS patient brochure about rhinoplasty
mentions the possibility of criticism or rejection by
friends or family if they feel threatened by the patient’s
new look. This type of reaction sometimes occurs with
rhinoplasty if the friends or relatives consider the
shape of the nose an important family or ethnic trait.
When the nose is reshaped or repaired from
inside, the scars are not visible, but if the surgeon
needs to make the incision on the outside of the nose,
there will be some slight scarring. In addition, tiny
blood vessels may burst, leaving small red spots on
the skin. These spots are barely visible but may be
permanent.
About 10% of patients require a second procedure; however, the corrections required are usually
minor.
Resources
PERIODICALS

Chou, T. D., W. T. Lee, S. L. Chen, et al. ‘‘Split Calvarial
Bone Graft for Chemical Burn-Associated Nasal
Augmentation.’’ Burns 30 (June 2004): 380–385.
Daniel, R. K., and J. W. Calvert. ‘‘Diced Cartilage Grafts in
Rhinoplasty Surgery.’’ Plastic and Reconstructive
Surgery 113 (June 2004): 2156–2171.
Honigman, R. J., K. A. Phillips, and D. J. Castle. ‘‘A Review
of Psychosocial Outcomes for Patients Seeking
Cosmetic Surgery.’’ Plastic and Reconstructive Surgery
113 (April 1, 2004): 1229–1237.
Raghavan, U., N. S. Jones, and T. Romo, 3rd. ‘‘Immediate
Autogenous Cartilage Grafts in Rhinoplasty after
GALE ENCYCLOPEDIA OF MEDICINE

American Society of Plastic Surgeons. Procedures:
Rhinoplasty. <http://www.plasticsurgery.org/public_education/procedures/Rhinoplasty.cfm>.

Dorothy Elinor Stonely
Rebecca J. Frey, PhD

Rhinovirus infection see Common cold
Rhytidoplasty see Face lift

Riboflavin deficiency
Definition
Riboflavin deficiency occurs when the chronic
failure to eat sufficient amounts of foods that contain
riboflavin produces lesions of the skin, lesions of
smooth surfaces in the digestive tract, or nervous
disorders.

Description
Riboflavin, also called vitamin B2, is a water-soluble vitamin. The recommended dietary allowance
(RDA) for riboflavin is 1.7 mg/day for an adult man
and 1.3 mg/day for an adult woman. The best sources
of this vitamin are meat, dairy products, and dark
green vegetables, especially broccoli. Grains and
legumes (beans and peas) also contribute riboflavin
to the diet. Riboflavin is required for the processing
of dietary fats, carbohydrates, and proteins to convert
these nutrients to energy. Riboflavin is also used for
the continual process of renewal and regeneration of
all cells and tissues in the body.
Riboflavin is sensitive to light. For this reason,
commercially available milk is sometimes supplied in
cartons, rather than in clear bottles. Riboflavin is not
rapidly destroyed by cooking. Milk contains about 1.7
mg riboflavin/kg. Cheese contains about 4.3 mg/kg,
while beef has 2.4 mg/kg and broccoli has about 2.0
3239

Riboflavin deficiency

KEY TERMS

Rickets

mg/kg. Apples, a food that is low in all nutrients,
except water, contains only 0.1 mg riboflavin per kg.

Causes and symptoms
A deficiency only in riboflavin has never occurred
in the natural environment. In contrast, diseases where
people are deficient in one vitamin, such as thiamin,
vitamin C, and vitamin D, for example, have been
clearly documented. Poorer populations in the
United States may be deficient in riboflavin, but
when this happens, they are also deficient in a number
of other nutrients as well. When riboflavin deficiency
is actually detected, it is often associated with low
consumption of milk, chronic alcoholism, or chronic
diarrhea.
The symptoms of riboflavin deficiency include:


swelling and fissuring of the lips (cheilosis)



ulceration and cracking of the angles of the mouth
(angular stomatitisis)



oily, scaly skin rashes on the scrotum, vulva, or area
between the nose and lips



inflammation of the tongue



red, itchy eyes that are sensitive to light

The nervous symptoms of riboflavin deficiency
include:


numbness of the hands



decreased sensitivity to touch, temperature, and
vibration

Diagnosis
Riboflavin status is diagnosed using a test conducted on red blood cells that measures the activity of
an enzyme called glutathione reductase. An extract of
the red blood cells is placed in two test tubes. One test
tube contains no added riboflavin, while the second
test tube contains a derivative of riboflavin, called
flavin adenine dinucleotide. The added riboflavin derivative results in little or no stimulation of enzyme
activity in patients with normal riboflavin levels. A
stimulation of 20% or less is considered normal.
A stimulation of over 20% means that the patient is
deficient in riboflavin.

KEY TERMS
Recommended dietary allowance—The recommended daily allowances (RDAs) are quantities of
nutrients of the diet that are required to maintain
human health. RDAs are established by the Food
and Nutrition Board of the National Academy of
Sciences and may be revised every few years. A
separate RDA value exists for each nutrient. The
RDA values refer to the amount of nutrient needed
to maintain health in a population of people. The
actual amounts of each nutrient required to maintain health in any specific individual differs from
person to person.
Water-soluble vitamin—Water-soluble vitamins
can be dissolved in water or juice. Fat-soluble vitamins can be dissolved in oil or in melted fat.

Prognosis
The prognosis for correcting riboflavin deficiency
is excellent.

Prevention
Riboflavin deficiency can be prevented by including milk, cheese, yogurt, meat, and/or certain vegetables in the daily diet. Of the vegetables, broccoli,
asparagus, and spinach are highest in riboflavin.
These vegetables have a riboflavin content that is
similar to that of milk, yogurt, or meat.
Resources
BOOKS

Brody, Tom. Nutritional Biochemistry. San Diego:
Academic Press, 1998.

Tom Brody, PhD

Rickets
Definition

Treatment
Riboflavin deficiency can be treated with supplemental riboflavin (0.5 mg/kg body weight per day)
until the symptoms disappear.
3240

Rickets is a childhood condition caused by serious
vitamin D deficiency. This lacking in vitamin D results
in weak, soft bones, along with slowed growth and
skeletal development. Rickets is, by definition, a
GALE ENCYCLOPEDIA OF MEDICINE

Description
Rickets occurs when the body has a severe lack of
vitamin D during the developmental years. Vitamin D
is essential to the development of strong, healthy
bones. A child with rickets can experience stunted
growth and will most likely be short in stature as an
adult. This is because, without proper vitamin D
levels, decreased mineralization of the bones at the
growth plate level affects the strength, size and shape
of the bones. A related condition called osteomalacia
can occur in adults with the same sort of vitamin D
deficiency, but osteomalacia occurs only in adulthood
after the growth plates of the bones have closed.
Most vitamin D is produced by the body,
although some can be directly supplied by diet. In
order to accomplish production of vitamin D, the
body requires both cholesterol and ultraviolet light.
Most often, the cholesterol comes from digesting animal tissue, oils, fats, and egg yolks. The ultraviolet
light is usually supplied by direct sunlight. Only
when this light is available can the skin alter the cholesterol molecule to make vitamin D. Children who do
not receive enough sunlight are at greater risk of developing rickets, as are children with darker skin, which
can block the ultraviolet rays. Vitamin D is found
naturally in the foods listed above, but more often
children receive vitamin D supplements through
foods which have had the vitamin added, as in milk
or infant formula.
Vitamin D is necessary in the body, because it can
be converted into a hormone which stimulates calcium
intake by the intestines. This conversion begins in the
liver, where vitamin D becomes a hormone called 25OH-D, and is completed when the kidneys convert 25OH-D into a hormone called 1,25-diOH-D. This is the
hormone that causes the intestines to absorb calcium
from the person’s diet. Without proper levels of vitamin D, there is not enough 1,25-diOH-D produced,
which results in lower levels of calcium in the body.
Adequate calcium is needed by the bones for both
development and maintenance.

Causes and symptoms
Rickets is directly caused by insufficient calcium
for bone mineralization during growth and development. This is caused by vitamin D deficiency which
can be a result of too little cholesterol, ultraviolet light,
or vitamin D supplement. During the Industrial
GALE ENCYCLOPEDIA OF MEDICINE

Revolution, rickets was quite common in cities
because pollution in the air blocked much of the sunlight needed for vitamin D production in the body.
There is also a hereditary type of rickets, called Xlinked hypophosphatemia, that causes the kidneys bo
be unable to retain phosphate.
The most commonly recognized symptoms of
rickets occur in the arms and legs, where stress on the
underdeveloped bones can cause bowing. Children
with rickets may feel pain or tenderness in the bones
of their arms, legs, spine, pelvis, and ribs. The skull
may develop an odd or asymmetrical shape. Calcium
levels in the blood will be low and overall growth is
often impaired.

Diagnosis
The initial approach to diagnosing rickets
involves a musculoskeletal examination followed by
an x ray is often. Affected children may have
obviously widened spaces between their joints or bowing of the bones in their arms and legs. Some children
may not experience normal dental development as
well. A doctor may also assess levels of serum calcium,
alkaline phosphatase and other indicator chemicals by
using a blood test. While calcium levels can be normal
or slightly low, alkaline phosphatase levels in a child
with rickets can be high even compared to a normal
adult. While x rays can prove misleading, diagnosis by
chemical analysis is highly accurate.

Treatment
The treatment for rickets primarily involves corrections of the conditions which led to the disorder.
This can be as simple as a change in diet to include
foods high in vitamin D such as milk, fish, or liver.
Treatment might also mean a gradual increase in the
amount sunlight received by the child. In more severe
cases, bracing or surgery may be necessary to aid in the
correction and repair of bones. Treatment is usually
mild and bone deformities usually reduce over time.

Alternative Treatment
There is currently little known about any alternative method for treating rickets. Treatments which
involve raising vitamin D levels and ultraviolet light
exposure are usually simple and effective.

Prognosis
Children with rickets are likely to suffer from
stunted growth, bone abnormalities and bone pain,
3241

Rickets

disorder which begins in childhood. If this problem
occurs only later in life it is known as osteomalacia.

Rickettsialpox

PERIODICALS

KEY TERMS
25-hydroxy-vitamin D—This is the form of vitamin
D that is measured in order to assess vitamin D
deficiency.
Cholesterol—A fat-soluble steroid alcohol (sterol)
found in animal fats and oils, and in egg yolks.
The human body needs cholesterol to produce
vitamin D.
Growth plate—The place in long bones where
growth occurs during childhood.
International unit (IU)—A measurement of biological activity in which one IU is equal to one mg
(milligram).
Mineralization—The process by which the body
uses minerals to build bone structure.
X-linked hypophosphatemia,—A type of rickets
caused by genetic factors which prevent the kidneys from retaining phosphate.

Spence, Jean, T. and Janet R. Serwint.‘‘Secondary
Prevention of Vitamin D-Deficiency Rickets.’’
Pediatrics. 113, no 5: (Jan 2004),129.
Wharton, Brian and Nick Bishop. ‘‘Rickets.’’ The Lancet
362 no9393: (Oct 2003). 1389.
OTHER

Finberg, Laurence. Rickets.E-Medicine December 18, 2003
[cited March 30, 2005]. <http://www.emedicine.com/
ped/topic2014.htm>.

Tish Davidson, A.M.

Rickets see Vitamin D deficiency
Rickettsia rickettsii infection see Rocky
Mountain spotted fever

Rickettsialpox
Definition

however these symptoms often disappear with treatment. In women, deformation of the pelvic bone structure can prevent vaginal childbirth later in life. Most
deformities correct with growth when proper levels of
vitamin D are restored and normal bone calcification
is maintained.

Prevention
Rickets caused by vitamin D deficiency is simple
to prevent. Commercially available infant formula is
usually fortified with more than enough vitamin D for
infants. For parents who breastfeed their children, it is
recommended by the U.S. Department of Health and
Human Services that children also receive 400 international units (10 micrograms) of vitamin D supplement. This is because human breast milk contains little
vitamin D. It is also important that children are
allowed decent amounts of sunlight. As little as twenty
minutes each day can be sufficient. For children living
in cities, where pollution is likely to block ultraviolet
light, and children with dark skin, which can block
ultraviolet light, vitamin D supplement is especially
important.
Resources
BOOKS

Hochber, Ze’ev, ed. Vitamin D and Rickets New York:
Karger 2003.
3242

Rickettsialpox is a relatively mild disease caused
by a member of the bacterial family called Rickettsia.
Rickettsialpox causes rash, fever, chills, heavy sweating, headache, eye pain (especially when exposed to
light), weakness, and achy muscles.

Description
Like other members of the family of Rickettsia,
the bacteria causing rickettsialpox live in mice. Tiny
mites feed on these infected mice, thus acquiring the
organism. When these mites feed on humans, the bacteria can be transmitted.
Rickettsialpox occurs mostly within cities. In the
United States, the disease has cropped up in such
places as New York City, Boston, Philadelphia,
Pittsburgh, and Cleveland. It has also been identified
in Russia, Korea, and Africa.

Causes and symptoms
The specific bacteria responsible for rickettsialpox
is called Rickettsia akari. A person contracts this bacteria through the bite of an infected mite. After a
person has been bitten by an infected mite, there is a
delay of about 10 days to three weeks prior to the onset
of symptoms.
The first symptom is a bump which appears at the
site of the original bite. The bump (papule) develops a
tiny, fluid-filled head (vesicle). The vesicle sloughs
GALE ENCYCLOPEDIA OF MEDICINE

Eschar—A crusty, blackish scab.
Papule—A bump on the skin.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Vesicle—A fluid-filled head on a papule.

away, leaving a crusty black scab in its place (eschar).
In about a week, the patient develops a fever, chills,
heavy sweating, headache, eye pain (especially when
exposed to light), weakness, and achy muscles. The
fever rises and falls over the course of about a weak. A
bumpy rash spreads across the body. Each individual
papule follows the same progression: papule, then
vesicle, then eschar. The rash does not affect the
palms of the hands or the soles of the feet.

Diagnosis
Most practitioners are able to diagnose rickettsialpox simply on the basis of its rising and falling
fever, and its characteristic rash. Occasionally, blood
will be drawn and tests performed to demonstrate the
presence of antibodies (immune cells directed against
specific bacterial agents) which would confirm a diagnosis of rickettsialpox.

Treatment
Because rickettsialpox is such a mild illness, some
practitioners choose to simply treat the symptoms
(giving acetaminophen for fever and achiness, pushing
fluids to avoid dehydration). Others will give their
patients a course of the antibiotic tetracycline, which
will shorten the course of the illness to about one to
two days.

Prognosis
Prognosis for full recovery from rickettsialpox is
excellent. No deaths have ever been reported from
this illness, and even the skin rash heals without
scarring.

Prevention
As with all mite- or tick-borne illnesses, prevention includes avoidance of areas known to harbor the
insects, and/or careful application of insect repellents.
Furthermore, because mice pass the bacteria on to the
mites, it is important to keep mice from nesting in or
around residences.
GALE ENCYCLOPEDIA OF MEDICINE

Rosalyn Carson-DeWitt, MD

Rifampin see Antituberculosis drugs
Ringing ears see Tinnitus

Ringworm
Definition
Ringworm is a common fungal infection of the
skin. The name is a misnomer since the disease is not
caused by a worm.

Description
More common in males than in females, ringworm is characterized by patches of rough, reddened
skin. Raised eruptions usually form the circular pattern that gives the condition its name. Ringworm may
also be referred to as dermatophyte infection.
As lesions grow, the centers start to heal. The
inflamed borders expand and spread the infection.
Types of ringworm
Ringworm is a term that is commonly used to
encompass several types of fungal infection.
Sometimes, however, only body ringworm is classified
as true ringworm.
Body ringworm (tinea corporis) can affect any
part of the body except the scalp, feet, and facial area
where a man’s beard grows. The well-defined, flaky
sores can be dry and scaly or moist and crusty.
Scalp ringworm (tinea capitis) is most common in
children. It causes scaly, swollen blisters or a rash that
looks like black dots. Sometimes inflamed and filled
with pus, scalp ringworm lesions can cause crusting,
flaking, and round bald patches. Most common in
black children, scalp ringworm can cause scarring
and permanent hair loss.
Ringworm of the groin (tinea cruris or jock itch)
produces raised red sores with well-marked edges. It
can spread to the buttocks, inner thighs, and external
genitals.
3243

Ringworm

Resources

KEY TERMS

Ringworm
Ringworm on a man’s chin. These infections are most common on the feet, scalp, or in toenails, but they can infect any part of the
skin. (Custom Medical Stock Photo. Reproduced by permission.)

Ringworm of the nails (tinea unguium) generally
starts at the tip of one or more toenails, which gradually thicken and discolor. The nail may deteriorate or
pull away from the nail bed. Fingernail infection is far
less common.

Causes and symptoms
Ringworm can be transmitted by infected people
or pets or by towels, hairbrushes, or other objects
contaminated by them. Symptoms include inflammation, scaling, and sometimes, itching.
Diabetes mellitus increases susceptibility to ringworm. So do dampness, humidity, and dirty, crowded
living areas. Braiding hair tightly and using hair gel
also raise the risk.

Treatment
Some infections disappear without treatment.
Others respond to such topical antifungal medications
as naftifine (Caldesene Medicated Powder) or tinactin
(Desenex) or to griseofulvin (Fulvicin), which is taken
by mouth. Medications should be continued for two
weeks after lesions disappear.
A person with body ringworm should wear loose
clothing and check daily for raw, open sores. Wet
dressings applied to moist sores two or three times a
day can lessen inflammation and loosen scales. The
doctor may suggest placing special pads between folds
of infected skin, and anything the patient has touched
or worn should be sterilized in boiling water.
Infected nails should be cut short and straight and
carefully cleared of dead cells with an emery board.
Patients with jock itch should:

Diagnosis
Diagnosis is based on microscopic examination of
scrapings taken from lesions. A dermatologist may
also study the scalp of a patient with suspected tinea
capitis under ultraviolet light.
3244



wear cotton underwear and change it more than once
a day



keep the infected area dry



apply antifungal ointment over a thin film of antifungal powder
GALE ENCYCLOPEDIA OF MEDICINE

Rinne test see Hearing tests with a tuning
fork
Ritonavir see Protease inhibitors
River blindness see Filariasis

Alternative treatment
The fungal infection ringworm can be treated with
homeopathic remedies. Among the homeopathic
remedies recommended are:


sepia for brown, scaly patches



tellurium for prominent, well-defined, reddish sores



graphites for thick scales or heavy discharge



sulphur for excessive itching.

Topical applications of antifungal herbs and essential oils also can help resolve ringworm. Tea tree oil
(Melaleuca spp.), thuja (Thuja occidentalis), and lavender
(Lavandula officinalis) are the most common. Two drops
of essential oil in 1/4 oz of carrier oil is the dose recommended for topical application. Essential oils should not
be applied to the skin undiluted. Botanical medicine can
be taken internally to enhance the body’s immune
response. A person must be susceptible to exhibit this
overgrowth of fungus on the skin. Echinacea(Echinacea
spp.) and astragalus (Astragalus membranaceus) are the
two most common immune-enhancing herbs. A wellbalanced diet, including protein, complex carbohydrates,
fresh fruits and vegetables, and good quality fats, is also
important in maintaining optimal immune function.

RMSF see Rocky Mountain spotted fever

Rocky Mountain spotted fever
Definition
Rocky Mountain spotted fever (RMSF) is a tickborne illness caused by a bacteria, resulting in a high
fever and a characteristic rash.

Description
The bacteria causing RMSF is passed to humans
through the bite of an infected tick. The illness begins
within about two weeks of such a bite. RMSF is the
most widespread tick-borne illness in the United
States, occurring in every state except Alaska and
Hawaii. The states in the mid-Atlantic region, the
Carolinas, and the Virginias have a great deal of tick
activity during the spring and summer months, and
the largest number of RMSF cases come from those
states. About 5% of all ticks carry the causative bacteria. Children under the age of 15 years have the
majority of RMSF infections.

Prognosis
Ringworm can usually be cured, but recurrence is
common. Chronic infection develops in one patient in
five.
It can take six to 12 months for new hair to cover
bald patches, and three to 12 months to cure infected
fingernails. Toenail infections do not always respond
to treatment.

Prevention
Likelihood of infection can be lessened by avoiding contact with infected people or pets or contaminated objects and staying away from hot, damp places.
Resources
OTHER

‘‘Ringworm.’’ YourHealth.com Page. April 7, 1998. <http://
www.yourhealth.com>.

Maureen Haggerty
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The bacterial culprit in RMSF is called Rickettsia
rickettsii. It causes no illness in the tick carrying it, and
can be passed on to the tick’s offspring. When a tick
attaches to a human, the bacteria is passed. The tick
must be attached to the human for about six hours for
this passage to occur. Although prompt tick removal
will cut down on the chance of contracting RMSF,
removal requires great care. If the tick’s head and
body are squashed during the course of removal, the
bacteria can be inadvertently rubbed into the tiny bite
wound.
Symptoms of RMSF begin within two weeks of
the bite of the infected tick. Symptoms usually begin
suddenly, with high fever, chills, headache, severe
weakness, and muscle pain. Pain in the large muscle
of the calf is very common, and may be particularly
severe. The patient may be somewhat confused and
delirious. Without treatment, these symptoms may
last two weeks or more.
3245

Rocky Mountain spotted fever

Shampoo containing selenium sulfide can help
prevent spread of scalp ringworm, but prescription
shampoo or oral medication is usually needed to cure
the infection.

Rocky Mountain spotted fever

The rash of RMSF is quite characteristic. It
usually begins on the fourth day of the illness, and
occurs in at least 90% of all patients with RMSF.
It starts around the wrists and ankles, as flat pink
marks (called macules). The rash spreads up the
arms and legs, toward the chest, abdomen, and
back. Unlike rashes which accompany various
viral infections, the rash of RMSF does spread to
the palms of the hands and the soles of the feet.
Over a couple of days, the macules turn a reddishpurple color. They are now called petechiae, which
are tiny areas of bleeding under the skin (pinpoint
hemorrhages). This signifies a new phase of the
illness. Over the next several days, the individual
petechiae may spread into each other, resulting in
larger patches of hemorrhage.
The most severe effects of RMSF occur due to
damage to the blood vessels, which become leaky. This
accounts for the production of petechiae. As blood
and fluid leak out of the injured blood vessels, other
tissues and organs may swell and become damaged,
and:


breathing difficulties may arise as the lungs are
affected.



heart rhythms may become abnormal



kidney failure occurs in very ill patients



liver function drops



the patient may experience nausea, vomiting, abdominal pain, and diarrhea



the brain may swell (encephalitis) in about 25% of
all RMSF patients (brain injury can result in seizures, changes in consciousness, actual coma, loss of
coordination, imbalance on walking, muscle
spasms, loss of bladder control, and various degrees
of paralysis)



the clotting system becomes impaired, and blood
may be evident in the stools or vomit

Diagnosis
Diagnosis of RMSF is almost always made on the
basis of the characteristic symptoms, coupled with
either a known tick bite (noted by about 60–70% of
patients) or exposure to an area known to harbor
ticks. Complex tests exist to nail down a diagnosis of
RMSF, but these are performed in only a few laboratories. Because the results of these tests take so long to
obtain, they are seldom used. This is because delaying
treatment is the main cause of death in patients with
RMSF.
3246

Treatment
It is essential to begin treatment absolutely as
soon as RMSF is seriously suspected. Delaying treatment can result in death.
Antibiotics are used to treat RMSF. The first
choice is a form of tetracycline; the second choice
(used in young children and pregnant women) is chloramphenicol. If the patient is well enough, treatment by
oral intake of medicine is perfectly effective. Sicker
patients will need to be given the medication through
a needle in the vein (intravenously). Penicillin and
sulfa drugs are not suitable for treatment of RMSF,
and their use may increase the death rate by delaying
the use of truly effective medications.
Very ill patients will need to be hospitalized in an
intensive care unit. Depending on the types of complications a particular patient experiences, a variety of
treatments may be necessary, including intravenous
fluids, blood transfusions, anti-seizure medications,
kidney dialysis, and mechanical ventilation (a breathing machine).

Alternative treatment
Although alternative treatments should never be
used in place of conventional treatment with antibiotics, they can be useful adjuncts to antibiotic therapy.
The use of Lactobacillus acidophilus and L. bifidus
supplementaion during and after antibiotic treatment
can help rebalance the intestinal flora. Acupuncture,
homeopathy, and botanical medicine can all be beneficial supportive therapies during recovery from this
disease.

Prognosis
Prior to the regular use of antibiotics to treat
RMSF, the death rate was about 25%. Although the
death rate from RMSF has improved greatly with an
understanding of the importance of early use of antibiotics, there is still a 5% death rate. This rate is
believed to be due to delays in the administration of
appropriate medications.
Certain risk factors suggest a worse outcome in
RMSF. Death rates are higher in males and increase as
people age. It is considered a bad prognostic sign to
develop symptoms of RMSF within only two to five
days of a tick bite.

Prevention
The mainstay of prevention involves avoiding
areas known to harbor ticks. However, because
GALE ENCYCLOPEDIA OF MEDICINE

Encephalitis—Inflammation of the tissues of the
brain.
Macule—A flat, discolored area on the skin.
Petechia—A small, round, reddish purple spot on
the skin, representing a tiny area of bleeding under
the skin.

many people enjoy recreational activities in just such
areas, the following steps can be taken:


Wear light colored clothing (so that attached ticks
are more easily noticed).



Wear long sleeved shirts and long pants; tuck the
pants legs into socks.



Spray clothing with appropriate tick repellents.



Examine. Anybody who has been outside for any
amount of time in an area known to have a population of ticks should examine his or her body carefully
for ticks. Parents should examine their children at the
end of the day.



Remove any ticks using tweezers, so that infection
doesn’t occur due to handling the tick. Grasp the
tick’s head with the tweezers, and pull gently but
firmly so that the head and body are entirely
removed.



Keep areas around homes clear of brush, which may
serve to harbor ticks.

I D A P . R O L F , P H . D . (1896–1979)
Born in New York City and raised in the Bronx, Ida P.
Rolf attended school in the New York area, graduating from
Barnard College in 1916. In 1920, she graduated from the
Columbia University College of Physicians and Surgeons
with a doctorate in biological chemistry. For the next 12
years, she worked in the departments of chemotherapy
and organic chemistry at the Rockefeller Institute. During
an extended leave of absence, she studied atomic physics
and mathematics at the Swiss Technical University in
Zurich and homeopathic medicine in Geneva. During
the 1930s, she studied osteopathy, chiropractic medicine,
tantric yoga, the Alexander Technique of tension reduction
through body movement, and the philosophy of altered
states of consciousness of Alfred H.S. Korzybski.
Her interest in body structure, movement, and
manipulation began after being kicked by a horse shortly
after graduating from Barnard. The accident left her with
acute pneumonia. Dissatisfied with conventional medical treatment, she began her quest for more natural and
effective ways of treating the body.
By 1940, Dr. Rolf had developed a technique of
body movement she called structural integration, also
known today as Rolfing. The therapy reshapes the body’s
muscular structure by applying pressure and energy, freeing the body from physical and emotional traumas. In
1977, she authored Rolfing: The Integration of Human
Structures. She continued to teach and refine her therapy
until her death in 1979. Dr. Rolf’s desire to teach her work
to others led to her establishing the Guild for Structural
Engineering, now known as the Rolf Institute of Structural
Integration, 205 Canyon Blvd., Boulder, CO 80302.

Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Rogaine see Minoxidil

Rolfing
Definition
Rolfing, also called Rolf therapy or structural
integration, is a holistic system of bodywork that
uses deep manipulation of the body’s soft tissue to
GALE ENCYCLOPEDIA OF MEDICINE

realign and balance the body’s myofascial structure.
Rolfing improves posture, relieves chronic pain, and
reduces stress.

Purpose
Rolfing helps to improve posture and bring the
body’s natural structure into proper balance and alignment. This can bring relief from general aches and
pains, improve breathing, increase energy, improve
self-confidence, and relieve physical and mental stress.
Rolfing has also been used to treat such specific physical problems as chronic back, neck, shoulder, and joint
pain, and repetitive stress injuries, including carpal tunnel syndrome. Many amateur and professional athletes,
including Olympic skaters and skiers, use Rolfing to
keep in top condition, to prevent injuries, and to more
quickly recover from injuries.
3247

Rolfing

KEY TERMS

Rolfing

Description
Origins
Ida Pauline Rolf (1896–1979) was a biochemist
from New York who developed structural integration
over the course of many years after an accident as a
young woman. She was kicked by a horse’s hoof on a
trip out West and developed symptoms resembling
those of acute pneumonia. She made her way to a
hospital in Montana, where she was treated by a physician who called in an osteopath to assist in her treatment. After the osteopath treated her, she was able to
breathe normally. After her return to New York, her
mother took her to a blind osteopath for further treatment. He taught her about the body’s structure and
function, after which Rolf became dissatisfied with
conventional medical treatment. Following completion of a doctorate in biochemistry from Columbia
University in 1920, Rolf studied atomic physics,
mathematics, and homeopathic medicine in Europe.
After 1928, when her father died and left her an inheritance that allowed her to pursue her own studies, she
explored various forms of alternative treatment,
including osteopathy, chiropractic medicine, tantric
yoga, the Alexander technique of tension reduction
through body movement, and Alfred Korzybski’s philosophy of altered states of consciousness.
By 1940, Rolf had synthesized what she had
learned from these various disciplines into her own
technique of body movement that she called structural
integration, which later became known as Rolfing.
During the Second World War, Rolf continued to
study with an osteopath in California named Amy
Cochran. In the mid-1960s, Gestalt therapist Fritz
Perls invited Rolf to Esalen, where she began to
develop a following among people involved in the
human potential movement. In 1977, she published
Rolfing: The Integration of Human Structures, the
definitive book on structural integration bodywork.
She continued to refine the therapy until her death in
1979. Rolf’s work is carried on through her Guild for
Structural Integration, now known as the Rolf
Institute of Structural Integration, which she founded
in 1971 in Boulder, Colo.
Rolfing is more than just a massage of the body’s
surface. It is a system that reshapes the body’s myofascial structure by applying pressure and energy,
thereby freeing the body from the effects of physical
and emotional traumas. Although Rolfing is used
extensively to treat sports injuries and back pain, it is
not designed as a therapy for any particular condition.
Rather, it is a systematic approach to overall wellness.
It works by counteracting the effects of gravity, which
3248

over time pulls the body out of alignment. This pull
causes the body’s connective tissue to become harder
and stiffer, and the muscles to atrophy. Signs of this
stiffening and contraction include slouching or an
overly erect posture.
Rolfing identifies the vertical line as the ideal that
the body should approximate. The mission statement
of the Guild for Structural Integration describes
Rolfing as ‘‘a method and a philosophy of personal
growth and integrity.... The vertical line is our fundamental concept. The physical and psychological
embodiment of the vertical line is a way of Being in
the physical world [that] forms a basis for personal
growth and integrity.’’
The basic ten
Basic Rolfing treatment consists of 10 sessions,
each lasting 60–90 minutes and costing about $100
each. The sessions are spaced a week or longer apart.
After a period of integration, specialized or advanced
treatment sessions are available. A ‘‘tuneup’’ session is
recommended every six months. In each session, the
Rolfer uses his or her fingers, hands, knuckles, and
elbows to rework the connective tissue over the entire
body. The tissues are worked until they become pliable, allowing the muscles to lengthen and return to
their normal alignment. The deep tissue manipulation
improves posture and agility, and increases the body’s
range of movement. Rolfers also believe that the
blocked energy accumulated in the tissue from emotional tension is released through Rolfing treatment,
causing the patient to feel more energetic and have a
more positive frame of mind.
Clients are asked to wait for a period of six to 12
months before scheduling advanced work, known as
the PostTen/Advanced Series. This period allows the
body to integrate the work done in the ‘‘Basic Ten.’’
Rolfing movement integration
Rolfing movement integration, or RMI, is
intended to help clients develop better awareness of
their vertical alignment and customary movement patterns. They learn to release tension and discover better
ways to use body movement effectively.
Rolfing rhythms
Rolfing rhythms are a series of exercises intended
to remind participants of the basic principles of
Rolfing: ease, length, balance, and harmony with
gravity. In addition, Rolfing rhythms improve the
client’s flexibility as well as muscle tone and
coordination.
GALE ENCYCLOPEDIA OF MEDICINE

Atrophy—A progressive wasting and loss of function of any part of the body.
Carpal tunnel syndrome—A condition caused by
compression of the median nerve in the carpal
tunnel of the hand, characterized by pain.
Fascia—The sheet of connective tissue that covers
the body under the skin and envelops every muscle, bone, nerve, gland, organ, and blood vessel.
Fascia helps the body to retain its basic shape.
Osteopathy—A system of medical practice that
believes that the human body can make its own
remedies to heal infection. It originally used manipulative techniques but also added surgical, hygienic, and medicinal methods when needed.
Parasympathetic nervous system—A part of the
autonomic nervous system that is concerned with
conserving and restoring energy. It is the part of the
nervous system that predominates in a state of
relaxation.
Structural integration—The term used to describe
the method and philosophy of life associated with
Rolfing. Its fundamental concept is the vertical line.

should consult with a medical practitioner before
undergoing Rolfing.

Side effects
There are no reported serious side effects associated with Rolfing when delivered by a certified practitioner to adults and juveniles.

Research and general acceptance
There is a growing amount of mainstream scientific research documenting the effectiveness of Rolf
therapy. A 1988 study published in the Journal of the
American Physical Therapy Association indicated
that Rolfing stimulates the parasympathetic nervous
system, which can help speed the recovery of
damaged tissue. Other studies done in the 1980s concerned the effectiveness of Rolfing in treating figure
skaters and children with cerebral palsy. In 1992 a
presentation was made to the National Center of
Medical Rehabilitation Research regarding Rolfing
in the treatment of degenerative joint disease. A
1997 article in The Journal of Orthopedic and Sports
Physical Therapy reported that Rolfing can provide
effective and sustained pain relief from lower back
problems.
Resources

Preparations
No pre-procedure preparations are needed to
begin Rolfing treatment. The treatment is usually
done on a massage table with the patient wearing
only undergarments. Prior to the first session, however, the client is asked to complete a health questionnaire, and photographs are taken to assist with
evaluation of his or her progress.

BOOKS

Levine, Andrew S., and Valerie J. Levine. The Bodywork and
Massage Sourcebook. Lincolnwood, IL: Lowell House.
1999.
ORGANIZATIONS

Rolf Institute of Structural Integration. 209 Canyon Blvd.
P.O. Box 1868. Boulder, CO 80306-1868. (303) 4495903. (800) 530-8875. <http://www.rolf.org>.

Ken R. Wells

Precautions
Since Rolfing involves vigorous deep tissue
manipulation, it is often described as uncomfortable
and sometimes painful, especially during the first several sessions. In the past decade, however, Rolfers
have developed newer techniques that cause less discomfort to participants. Since Rolfing is a bodywork
treatment that requires the use of hands, it may be a
problem for people who do not like or are afraid of
being touched. It is not recommended as a treatment
for any disease or a chronic inflammatory condition
such as arthritis, and can worsen such a condition.
Anyone with a serious medical condition, including
heart disease, diabetes, or respiratory problems,
GALE ENCYCLOPEDIA OF MEDICINE

Root canal treatment
Definition
Root canal treatment, also known as endodontic
treatment, is a dental procedure in which the diseased
or damaged pulp (core) of a tooth is removed and the
inside areas (the pulp chamber and root canals) are
filled and sealed.
3249

Root canal treatment

KEY TERMS

Root canal treatment

Infection
Enamel

Drill
Rubber
dam

Pulp cavity

Figure A

Figure B

Antibiotic
paste

Temporary
filling

Figure C

Root canal treatment is a dental procedure in which the diseased pulp of a tooth is removed and the inside areas are filled and
sealed. In figure A, the infection can be seen above the pulp cavity. The dentist drills into the enamel and the pulp cavity is
extracted (figure B). Finally, the dentist fills the pulp cavity with antibiotic paste and a temporary filling (figure C). (Illustration by
Electronic Illustrators Group.)

Purpose
Inflamed or infected pulp (pulpitis) most often
causes a toothache. To relieve the pain and prevent
further complications, the tooth may be extracted
(surgically removed) or saved by root canal treatment.
Root canal treatment has become a common dental
procedure; more than 14 million are performed every
year, with a 95% success rate, according to the
American Association of Endodontists.

Precautions
Once root canal treatment is performed, the
patient must have a crown placed over the tooth to
protect it. The cost of the treatment and the crown
may be expensive. However, replacing an extracted
tooth with a fixed bridge, a removable partial denture,
or an implant to maintain the space and restore the
chewing function is typically even more expensive.

Description
Root canal treatment may be performed by a
general dentist or by an endodontist, a dentist who
specializes in endodontic (literally ‘‘inside of the
tooth’’) procedures. Inside the tooth, the pulp’s soft
tissue contains the blood supply, by which the
3250

tooth gets its nutrients, and the nerve, by which the
tooth senses hot and cold. This tissue is vulnerable to
damage from deep dental decay, accidental injury,
tooth fracture, or trauma from repeated dental procedures (such as multiple fillings over time). If a tooth
becomes diseased or injured, bacteria build up inside
the pulp, spreading infection from the natural
crown of the tooth to the root tips in the jawbone.
Pus accumulates at the ends of the roots, forming a
painful abscess which can damage the bone supporting
the teeth. Such an infection may produce pain that is
severe, constant, or throbbing, as well as prolonged
sensitivity to heat or cold, swelling and tenderness
in the surrounding gums, facial swelling, and discoloration of the tooth. However, in some cases, the
pulp may die so gradually that there is little noticeable
pain.
Root canal treatment is performed under local
anesthesia. A thin sheet of rubber, called a rubber
dam, is placed in the mouth to isolate the tooth. The
dentist removes any tooth decay and makes an opening
through the natural crown of the tooth into the pulp
chamber. Creating this access also relieves the pressure
inside the tooth and can dramatically ease pain.
The dentist determines the length of the root
canals, usually with a series of x rays. Small wire-like
GALE ENCYCLOPEDIA OF MEDICINE

Once the canals are completely clean, they are
filled with gutta percha and a sealer cement to prevent bacteria from entering the tooth in the future. A
metal post may be placed in the pulp chamber for
added structural support and better retention of
the crown restoration. The tooth is protected by a
temporary filling or crown until a permanent restoration may be made. This restoration is usually a gold
or porcelain crown, although it may be a gold inlay,
or an amalgam or composite filling (paste fillings that
harden).

Preparation
There is no typical preparation for root canal
treatment. Once the tooth is opened to drain, the
dentist may prescribe an antibiotic, then the patient
should take the full prescribed course. With the infection under control, local anesthetic is more effective,
so that the root canal procedure may be performed
without discomfort.

Aftercare
The tooth may be sore for several days after filling. Pain relievers, such as ibuprofen (Advil, Motrin)
may be taken to ease the soreness. The tissues around
the tooth may also be irritated. Rinsing the mouth
with hot salt water several times a day will help.
Chewing on that side of the mouth should be avoided
for the first few days following treatment. A follow-up
appointment should be scheduled with the dentist for
six months after treatment to make sure the tooth and
surrounding structures are healthy.

Risks
There is a possibility that the root canal treatment
will not be successful the first time. If infection and
inflammation recur and an x ray indicates retreatment
is feasible, the old filling material is removed and the
canals are thoroughly cleaned out. The dentist will try
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Abscess—A hole in the tooth or gum tissue filled
with pus as the result of infection. Its swelling exerts
pressure on the surrounding tissues, causing pain.
Apicoectomy—Also called root resectioning. The
root tip of a tooth is accessed in the bone and a
small amount is shaved away. The diseased tissue is
removed and a filling is placed to reseal the canal.
Crown—The natural crown of a tooth is that part of
the tooth covered by enamel. Also, a restorative
crown is a protective shell that fits over a tooth.
Endodontic—Pertaining to the inside structures of
the tooth, including the dental pulp and tooth root,
and the periapical tissue surrounding the root.
Endodontist—A dentist who specializes in the
diagnosis and treatment of disorders affecting the
inside structures of the tooth.
Extraction—The surgical removal of a tooth from
its socket in the bone.
Gutta percha—An inert latex-like substance used
for filling root canals.
Pulp—The soft innermost layer of a tooth, containing blood vessels and nerves.
Pulp chamber—The area within the natural crown
of the tooth occupied by dental pulp.
Pulpitis—Inflammation of the pulp of a tooth involving the blood vessels and nerves.
Root canal—The space within a tooth that runs
from the pulp chamber to the tip of the root.
Root canal treatment—The process of removing
diseased or damaged pulp from a tooth, then filling
and sealing the pulp chamber and root canals.

to identify and correct problems with the first root
canal treatment before filling and sealing the tooth a
second time.
In cases where an x ray indicates that retreatment
cannot correct the problem, endodontic surgery may
be performed. In a procedure called an apicoectomy,
or root resectioning, the root end of the tooth is
accessed in the bone, and a small amount is shaved
away. The area is cleaned of diseased tissue and a
filling is placed to reseal the canal.
In some cases, despite root canal treatment and
endodontic surgery, the tooth dies anyway and must
be extracted.
3251

Root canal treatment

files are then used to clean the entire canal space of
diseased pulp tissue and bacteria. The debris is flushed
out with large amounts of water (irrigation). The
canals are also slightly enlarged and shaped to receive
an inert (non-reactive) filling material called gutta
percha. However, the tooth is not filled and permanently sealed until it is completely free of active infection. The dentist may place a temporary seal, or leave
the tooth open to drain, and prescribe an antibiotic to
counter any spread of infection from the tooth. This is
why root canal treatment may require several visits to
the dentist.

Rosacea

Normal results
With successful root canal treatment, the tooth
will no longer cause pain. However, because it does
not contain an internal nerve, it no longer has sensitivity to hot, cold, or sweets. These are signs of dental
decay, so the patient must receive regular dental
check-ups with periodic x rays to avoid further disease
in the tooth. The restored tooth could last a lifetime;
however, with routine wear, the filling or crown may
eventually need to be replaced.
Resources
ORGANIZATIONS

American Association of Endodontists. 211 East Chicago
Ave., Ste. 1100, Chicago, IL 60611-2691. (800) 8723636. <http://www.aae.org>.
American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.
OTHER

‘‘Endodontic (Root Canal) Therapy.’’ Tooth Talk and Your
Health with Dr. Frank Gober. <http://
www.toothtalk.com>.
‘‘Root Canal Treatment.’’ Annapolis Endodontics.
<http://users.erols.com/canals/index.html>.
‘‘Root Canal Treatment.’’ Value Added Benefits.
<http://www.vab.com>.
Thivierge, Bethany. ‘‘What is the Value (and Cost) of a
Root Canal?’’ A Healthy Me Page. <http://
www.ahealthyme.com/topic/rootcanal>.

Bethany Thivierge

Rosacea
Definition
Rosacea is a skin disease typically appearing in
people during their 30s and 40s. It is marked by redness (erythema) of the face, flushing of the skin, and
the presence of hard pimples (papules) or pus-filled
pimples (pustules), and small visible spider-like veins
called telangiectasias. In later stages of the disease, the
face may swell and the nose may take on a bulb-like
appearance called rhinophyma.

Description
Rosacea produces redness and flushing of the
skin, as well as pustules and papules. Areas of the
face, including the nose, cheeks, forehead, and chin,
3252

are the primary sites, but some people experience
symptoms on their necks, backs, scalp, arms, and legs.
The similarity in appearance of rosacea to acne led
people in the past to erroneously call the disease acne
rosacea or adult acne. Like acne, the skin can have
pimples and papules. Unlike acne, however, people
with rosacea do not have blackheads.
In early stages of rosacea, people typically experience repeated episodes of flushing. Later, areas of the
face are persistently red, telangiectasia appear on the
nose and cheeks, as well as inflamed papules and
pustules. Over time, the skin may take on a roughened,
orange peel texture. Very late in the disorder, a small
group of patients with rosacea will develop rhinophyma, which can give the nose a bulb-like look.
Up to one half of patients with rosacea may
experience symptoms related to their eyes. Ocular
rosacea, as it is called, frequently precedes the other
manifestations on the skin. Most of these eye symptoms do not threaten sight, however. Telangiectasia
may appear around the borders of the eyelid, the eyelids may be chronically inflamed, and small lumps
called chalazions may develop. The cornea of the
eye, the transparent covering over the lens, can also
be affected, and in some cases vision will be affected.

Causes and symptoms
There is no known specific cause of rosacea. A
history of redness and flushing precedes the disease in
most patients. The consensus among many experts is
that multiple factors may lead to an overreaction of
the facial blood vessels, which triggers flushing. Over
time, persistent episodes of redness and flushing leave
the face continually inflamed. Pimples and blood-vessel changes follow.
Certain genetic factors may also come into play,
although these have not been fully described. The
disease is more common in women and light-skinned,
fair-haired people. It may be more common in people
of Celtic background, although this is an area of disagreement among experts.
Certain antibiotics are useful in the treatment of
rosacea, leading some researchers to suspect a bacterium or other infectious agent may be the cause. One of
the newest suspects is a bacterium called Helicobacter
pylori, which has been implicated in causing many
cases of stomach ulcers but the evidence here is mixed.
Other investigators have observed that a particular parasite, the mite Demodex folliculorum, can be
found in areas of the skin affected by rosacea. The
mite can also be detected, however, in the skin of
GALE ENCYCLOPEDIA OF MEDICINE

Rosacea

people who do not have the disease. It is likely that the
mite does not cause rosacea, but merely aggravates it.

Diagnosis
Diagnosis of rosacea is made by the presence of
clinical symptoms. There is no specific test for the
disease. Episodes of persistent flushing, redness
(erythema) of the nose, cheeks, chin, and forehead,
accompanied by pustules and papules are hallmarks
of the disease. A dermatologist will attempt to rule out
a number of other diseases that have similar symptoms. Acne vulgaris is perhaps the disorder most
commonly mistaken for rosacea, but redness and
spider-like veins are not observed in patients with
acne. Blackheads and cysts, however, are seen in
acne patients, but not in those with rosacea.
Other diseases that produce some of the same
symptoms as rosacea include perioral dermatitis and
systemic lupus erythematosus.

Treatment
The mainstay of treatment for rosacea is oral antibiotics. These appear to work by reducing inflammation in the small blood vessels and structure of the skin,
not by destroying bacteria that are present. Among the
more widely used oral antibiotics is tetracycline. In
many patients, antibiotics are effective against the
papules and pustules that can appear on the face, but
they appear less effective against the background
redness, and they have no effect on telangiectasia.
Patients frequently take a relatively high dose of antibiotics until their symptoms are controlled, and then
they slowly reduce their daily dose to a level that just
keeps their symptoms in check. Other oral antibiotics
used include erythromycin and minocycline.

Rosacea on a woman’s cheek. (Custom Medical Stock Photo.
Reproduced by permission.)

particularly in women of childbearing age. They must
agree to a reliable form of contraception, because the
drug is known to cause birth defects.
Topical vitamin A derivatives that are used in the
treatment of acne also may have a role in the treatment
of rosacea. Accumulating evidence suggests that topical isotretinoin and topical azelaic acid can reduce the
redness and pimples. Some patients who use these
medications experience skin irritation that tends to
resolve with time.
For later stages of the disorder, a surgical procedure may be needed to improve the appearance of the
skin. To remove the telangiectasias, a dermatologist
may use an electrocautery device to apply a current to
the blood vessel in order to destroy it. Special lasers,
called tunable dye lasers, can also be adjusted to selectively destroy these tiny blood vessels.
A variety of surgical techniques can be used to
improve the shape and appearance of a bulbous nose
in the later stages of the disease. Surgeons may use a
scalpel or laser to remove excess tissue from the nose
and restore a more natural appearance.

Some patients are concerned about long-term use of
oral antibiotics. For them, a topical agent applied
directly to the face may be tried in addition to an oral
antibiotic, or in its place. Topical antibiotics are also
useful for controlling the papules and pustules of rosacea, but do not control the redness, flushing, and telangiectasias. The newest of these topical agents is
metronidazole gel, which can be applied twice daily.
Like the oral antibiotics, topical preparations appear to
work by reducing inflammation, not by killing bacteria.

Alternative treatments have not been extensively
studied in rosacea. Some reports advocate gentle circular massage for several minutes daily to the nose,
cheeks, and forehead. Scientifically controlled studies
are lacking, however.

Vitamin A derivatives, called retinoids, also
appear useful in the treatment of rosacea. An oral
retinoid, called isotretinoin, which is used in severe
cases of acne also reduces the pustules and papules in
severe cases of rosacea that do not respond to antibiotics. Isotretinoin must be taken with care, however,

Many people are able to avoid outbreaks by reducing things that trigger flushing. Alcoholic beverages,
hot beverages, and spicy foods are among the more
common factors in the diet that can provoke flushing.
Reducing or eliminating these items in the diet can help
limit rosacea outbreaks in many people. Exposure to

GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment

3253

Roseola

Use sunscreen

KEY TERMS
Blackhead—A plug of fatty cells capped with a
blackened mass.
Erythema—A diffuse red and inflamed area of the
skin.

Limiting exposure of the face to excesses of heat
and cold can also help. A sunscreen with a skin protection factor (SPF) of 15 or greater used daily can limit
the damage to the skin and small blood vessels caused
by the sun, and reduce outbreaks.

Papule—A small hard elevation of the skin.
Pustule—A small pus-filled elevation of the skin.

Resources

Retinoid—A synthetic vitamin A derivative used in
the treatment of a variety of skin disorders.

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050.
<http://www.aad.org>.
National Rosacea Society. 800 S. Northwest Highway, Suite
200, Barrington, IL 60010. (888) 662-5874.
<http://www.rosacea.org>.

Rhinophyma—Long-term swelling and overgrowth
in skin tissue of the nose that leaves it with a knobby
bulb-like look.
Telangiectasia—Small blood veins visible at the
surface of the skin of the nose and cheeks.

heat, cold, and sunlight are also known triggers of
flushing. The specific things that provoke flushing
vary considerably from person to person, however. It
usually takes some trial and error to figure these out.
A deficiency in hydrochloric acid (HCl) in the
stomach may be a cause of rosacea, and supplementation with HCl capsules may bring relief in some cases.

Prognosis
The prognosis for controlling symptoms of rosacea and improving the appearance of the face is good.
Many people require life-long treatment and achieve
good results. There is no known cure for the disorder.

Prevention
Rosacea cannot be prevented, but once correctly
diagnosed, outbreaks can be treated and repeated episodes can be limited.
Use mild soaps
Avoiding anything that irritates the skin is a good
preventive measure for people with rosacea. Mild
soaps and cleansers are recommended. Astringents
and alcohol should be avoided.
Learn what triggers flushing
Reducing factors in the diet and environment that
cause flushing of the face is another good preventive
strategy. Alcoholic and hot beverages, and spicy foods
are among the more common triggers.
3254

ORGANIZATIONS

Richard H. Camer

Rosary bead esophagus see Diffuse esophageal spasm

Roseola
Definition
Roseola is a common disease of babies or young
children, in which several days of very high fever are
followed by a rash.

Description
Roseola is an extraordinarily common infection,
caused by a virus. About 90% of all children have been
exposed to the virus, with about 33% actually demonstrating the syndrome of fever followed by rash.
The most common age for a child to contract
roseola is between six and twelve months. Roseola
infection strikes boys and girls equally. The infection
may occur at any time of year, although late spring
and early summer seem to be peak times for it.

Causes and symptoms
About 85% of the time, roseola is caused by a
virus called Human Herpesvirus 6, or HHV-6.
Although the virus is related to those herpesviruses
known to cause sores on the lips or genitalia, HHV-6
causes a very different type of infection. HHV-6 is
believed to be passed between people via infected saliva. A few other viruses (called enteroviruses) can
GALE ENCYCLOPEDIA OF MEDICINE

Roseola

KEY TERMS
Jaundice—The development of a yellowish tone to
the skin and the whites of the eyes, caused by poor
liver function.
Mononuclosis—An infection which causes swelling of lymph nodes, spleen, and liver, usually
accompanied by extremely sore throat, fever,
headache, and intense long-lasting fatigue.

Roseola rash on infant’s back and shoulders. (Custom Medical
Stock Photo. Reproduced by permission.)

produce a similar fever-then-rash illness, which is
usually also called roseola.
Researchers believe that it takes about 5-15 days
to develop illness after having been infected by HHV6. Roseola strikes suddenly, when a previously-well
child spikes an impressively high fever. The temperature may reach 1068F. As is always the case with
sudden fever spikes, the extreme change in temperature may cause certain children to have seizures.
About 5-35% of all children with roseola will have
these ‘‘febrile seizures.’’
The most notable thing about this early phase of
roseola is the absence of symptoms, other than the
high fever. Although some children have a slightly
reddened throat, or a slightly runny nose, most children have no symptoms whatsoever, other than the
sudden development of high fever. This fever lasts
for between three and five days.
Somewhere around the fifth day, a rash begins on
the body. The rash is usually composed of flat pink
patches or spots, although there may be some raised
patches as well. The rash usually starts on the chest,
back, and abdomen, and then spreads out to the arms
and neck. It may or may not reach the legs and face.
The rash lasts for about three days, then fades.
Very rarely, roseola will cause more serious disease. Patients so afflicted will experience significant
swelling of the lymph nodes, the liver, and the spleen.
The liver may become sufficiently inflamed to interfere
with its functioning, resulting in a yellowish color to
the whites of the eyes and the skin (jaundice). This
syndrome (called a mononucleosis-like syndrome,
after the disease called mononucleosis that causes
many of the same symptoms) has occurred in both
infants and adults.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
The diagnosis of roseola is often made by carefully
examining the feverish child to make sure that other
illnesses are not causing the temperature spike. Once it
is clear that no pneumonia, ear infection, strep throat,
or other common childhood illness is present, the
practitioner usually feels comfortable waiting to see
if the characteristic rash of roseola begins.

Treatment
There are no treatments available to stop the
course of roseola. Acetaminophen or ibuprofen is
usually given to try to lower the fever. Children who
are susceptible to seizures may be given a sedative
medication when the fever first spikes, in an attempt
to prevent such a seizure.

Prognosis
Children recover quickly and completely from
roseola. The only complications are those associated
with seizures, or the rare mononucleosis-like
syndrome.

Prevention
Other than the usual good hygiene practices
always recommended to decrease the spread of viral
illness, no methods are available to specifically prevent
roseola.
Resources
BOOKS

Kohl, Steve. ‘‘Human Herpesvirus 6.’’ In Nelson Textbook of
Pediatrics, edited by Richard E. Behrman.
Philadelphia: W. B. Saunders Co., 1996.

Rosalyn Carson-DeWitt, MD

Roseola infantum see Roseola
3255

Ross River Virus

Ross River Virus
Definition
Ross River Virus (RRV) is Australia’s most common and widespread mosquito-borne pathogen. Also
known as RRV disease, it can cause debilitating polyarthritis, rash, fever, and constitutional symptoms.

Description
Originally known as epidemic polyarthritis, RRV
is a member of the Togaviridae family of arboviruses.
RRV is transmitted in an animal host-vector-human
cycle, where the vector is the mosquito. Serological
investigations have indicated that native macropods
are the main vertebrate hosts of RRV, although other
animals can become infected as well. The RRV lives
in the blood stream of an infected animal. When a
mosquito feeds on the infected animal, the virus is
transmitted to the insect where it rapidly multiplies.
The virus is then passed onto the next animal or person
the mosquito bites. It has been proposed that humanmosquito-human transmission can occur during RRV
epidemics. One-third of all humans bitten by an
infected mosquito will develop the RRV disease.
The RRV disease occurs throughout continental
Australia. However, the majority of RRV infections
occur in the northern states and along costal areas; in
particular, the state of Queensland. Of the 4,800 cases
reported annually in Australia, approximately 2,700
of these occur in Queensland. In addition to these
cases, many more go unreported. Infection can occur
year round, but outbreaks typically coincide with the
increased mosquito activity of the wet season (between
late November and the end of April). Also, areas with
intensive irrigation and those near salt marches have
higher mosquito populations, and, thus, tend to exhibit a higher number of RRV cases.
In addition to continental Australia, RRV is endemic to the Solomon Islands, East Timor, Papua New
Guinea, and the adjacent islands of Indonesia.
Epidemics have also been reported in the Cook
Islands, Fiji, French Polynesia, New Caledonia, and
Western Samoa.

Causes and symptoms
Many people that are infected with RRV will
never develop symptoms. However, 25% to 45% of
cases will develop symptoms within three days to three
weeks (averaging nine days) of the infection.
Symptoms will vary between patients, but typically
3256

include arthralgia, arthritis, myalgia, skin rash, fever,
fatigue, headache, and swollen lymph nodes. Tingling
and pain in the palms of the hands and soles of the feet
can accompany these symptoms. Other, less frequent,
symptoms can include general malaise, nausea, sore
eyes, and sore throat.
Most patients with RRV disease (83% to 98%)
experience symptoms of polyarthritis involving the
wrists, knees, ankles, and small joints of the extremities. Less frequently affected joints include the elbows,
toes, tarsal joints, vertebral joints, shoulders, and hips.
Symptoms can range from restricted joint movement
to prominent swell and severe pain. Although severe
joint pain can last for only 2 to 6 weeks, over half of
patients will continue to experience joint pain for 6 to
12 months after RRV infection. Symptoms typically
diminish over time, but relapses are common and have
been known to persist for several years. This persistent
polyarthritis can lead to fatigue and myalgia, contributing to RRV diseases high morbidity.

Diagnosis
Diagnosis usually consists of serological tests to
determine the presence and increase of RRV antibodies. Samples should be taken during the acute or
convalescent stages of the illness. Testing will help
clinicians differentiate between RRV disease and
Barmah Forest virus disease, a very similar arbovirus.
Virological tests can help distinguish between RRV
disease and other causes of arthritis.

Treatment
No cure for RRV disease currently exists, so only
its symptoms can be treated. In one of the few studies
on RRV disease treatment, Cordon and Rouse (1995)
found that roughly one-third of patients (36.4%)
reported that nonsteroidal anti-inflammatory drugs
(NSAIDS) provided them with the best symptomatic
relief. In addition to NSAIDS, others patients found
that rest (24.1%), aspirin and paracetamol (16.4%), or
physical therapies (10.3%), such as hydrotherapy,
massage, and physiotherapy, were their only source
of symptom relief. Unfortunately, 20% of patients
found none of these interventions effective. Health
providers typically use one or a combination of these
treatments for their patients. In particular, paracetamol has been found to be effective for treating the pain
and fever associated with RRV disease.
Although some clinicians have found the use of
oral corticosteroid useful and effective, this practice is
considered unwise and unnecessary. The adverse
GALE ENCYCLOPEDIA OF MEDICINE

Arthralgia—Sharp, severe pain, extending along a
nerve or group of nerves, experienced in a joint
and/or joints.
Abrovirus viruses—Also known as arthropodborne viruses, these viruses are maintained in
nature through biological transmission between vertebrate hosts and blood-feeding arthropods. Infection
occurs when an infected arthropod, such as a
mosquito, feeds off a vertebrate, such as a human.
Macropods—Derived from the Greek, macropod
literally means ‘‘large footed.’’ Macropods are marsupials belonging to the family Macropodidae,
which includes kangaroos, wallabies, tree kangaroos, pademelons, and several others.
Myalgia—Muscular pain or tenderness, typically of
a diffuse and/or nonspecific nature.
Polyarthritis—A nonspecific term for arthritis
involving two or more joints, typically associated
with auto-immune forms of arthritis. Symptoms
usually include pain, inflammation, and/or swelling in multiple joints.

effects associated with corticosteroids may outweigh
their benefits, and may even worsen the RRV disease.
More study is required on this and other treatment
interventions of RRV disease.

Prognosis
Patients infected with RRV disease will fully
recover within four to seven months. Although milder
cases can recover within a few weeks, many cases have
persisted for several years. Only the symptoms can be
treated during this time, not the disease. Fortunately,
RRV infection usually provides the patient with lifelong immunity to future infection.

Prevention
Prevention techniques of RRV typically coincide
with measures used to avoid mosquito bites; the primary
source of the virus. These include the use of insect
repellant (with 5% to 20% DEET) on exposed body
parts, wearing loose-fitting clothes over the limbs and
torso while outdoors, using mosquito coils and/or citronella candles outdoors, and limiting outdoor activities
during peak biting periods and/or in areas with high
mosquito density. While camping outdoors, knockdown spray or bed netting with pyrethrum is suggested.
GALE ENCYCLOPEDIA OF MEDICINE

Additional steps for reducing risk of being bitten include
using screens in homes and removing mosquitobreeding areas near the home, such as uncovered water
containers and old tires. Mosquito eradication programs can assist in reducing insect populations. An
RRV vaccine is currently being developed.
Resources
BOOKS

Kay B.H., and J.G. Aaskov. ‘‘Ross River Virus (Epidemic
Polyarthritis)’’. In The Arboviruses: Epidemiology and
Ecology (Vol. IV), edited by T.P. Monath. Boca Raton,
FL: CRC Press, 1989, pp. 93-112.
PERIODICALS

Harley, D., A. Sleigh, S. Ritchie. ‘‘Ross River Virus
Transmission, Infection, and Disease: A Cross-disciplinary Review. ’’ Clinical Microbiology Reviews 14
(October 2001): 909-932.
Harley, D., S. Ritchie, C. Bain, and A. Sleigh. ‘‘Risks for
Ross River Virus Disease in Tropical Australia.’’
International Journal of Epidemiology (January 26
2005): 1-8.
Flexman, J., D. Smith, J. Mackenzie, J. Fraser, S. Bass, L.
Hueston, et al. ‘‘A Comparison of the Diseases Caused
by Ross River Virus and Barmah Forest Virus.’’ Medical
Journal of Australia 169 (August 1998):159-163.
Hills, S. ‘‘Ross River Virus and Barmah Forest Virus
Infection.’’ Australian Family Physician 25 (December
1996):1822-1824.
OTHER

‘‘Ross River Virus Infection- Fact Sheet’’ Australian
Government- Department of Health and Ageing <http://
www.health.gov.au/internet/wcms/Publishing.nsf/
Content/health-arbovirus-pdf-fsrossriver.htm>.

Jason Fryer

Rotator cuff injury
Definition
A rotator cuff injury is a tear or inflammation of
the rotator cuff tendons in the shoulder.

Description
Rotator cuff injury is known by several names,
including pitcher’s shoulder, swimmer’s shoulder, and
tennis shoulder. As these names imply, the injury
occurs most frequently in athletes practicing sports
that require the arm to be moved over the head repeatedly, such as pitching, swimming, tennis, and weight
3257

Rotator cuff injury

KEY TERMS

Rotator cuff injury

lifting. Rotator cuff tendonitis is an inflammation of
the shoulder tendons while a rotator cuff tear is a
ripping of one or more of the tendons.
The tendons of four muscles make up the rotator
cuff. The muscles are the supraspinatus, infraspinatus,
teres minor, and subscapularis. The tendons attach the
muscles to four shoulder bones: the shoulder blade
(scapula), the upper arm bone (humerus), and the
collarbone (clavicle.) The rotator cuff tendons can
also degenerate due to age, usually starting around
age 40. Rotator cuff injury may also be caused by
falling on the outstretched arm or joint of the elbow.
Either of these may produce enough force to drive the
humerus into the shoulder socket.

Causes and symptoms
Some areas of the rotator cuff tendons have poor
blood supply. Thus, the tissue is very slow to heal and
maintain itself during normal use. Tearing and inflammation in athletes is usually due to hard and repetitive
use, especially in baseball pitchers. In non-athletes
over age 40, the injuries usually occur as a result of
lifting heavy objects. The two primary symptoms are
pain and weakness in the shoulder or arm, especially
with arm movement or at night. A partial tear may
cause pain but still allow normal arm movement. A
complete tear usually leaves the injured person unable
to raise the arm away from the side.

Diagnosis
Diagnosis is usually made after a physical examination, often by a sports medicine physician. X rays
are also sometimes used in diagnosis as well as an
arthrogram. However, the arthrogram is an invasive
procedure and may be painful afterwards. For this
reason, magnetic resonance imaging (MRI) is preferred
to determine tendon tears as it also show greater detail
than the arthrogram.

Treatment
The primary treatment is resting the shoulder and,
for minor tears and inflammation, applying ice packs.
Anti-inflammatory medications may also be prescribed. As soon as pain decreases, physical therapy
is usually started to help regain normal motion. If pain
persists after several weeks, the physician may inject
cortisone into the affected area.
Serious tears to the rotator cuff tendons usually
require surgery to repair. An instrument called an
arthroscope is used to view the shoulder joint and
3258

KEY TERMS
Arthrogram—A test done by injecting dye into the
shoulder joint and then taking x-rays. Areas where
the dye leaks out indicate a tear in the tendons.
Arthroscope—An instrument for the visual examination of the interior of a joint.
Arthroscopy—Examination of a joint with an
arthroscope or joint surgery using an arthroscope.
Cortisone—A hormone produced naturally by the
adrenal glands or made synthetically.
Magnetic resonance imaging (MRI) scan—A special radiological test that uses magnetic waves to
create pictures of an area, including bones, muscles, and tendons.
Spur—Any projection from a bone.

confirm the presence of a tear. The arthroscope can
also be used to remove any bone spurs that may be
present in the shoulder area. Current arthroscopic procedures usually involve a 2 in (5.1 cm) incision in the
outer shoulder. Through this incision the torn rotator
edge may be reattached to the humerus with stitches.

Alternative treatment
There are no effective alternative medicine treatments for rotator cuff injuries.

Prognosis
The prognosis for recovery from minor rotator
cuff injuries is excellent. For serious injuries, the prognosis is usually good, some six weeks of physical therapy being required following surgery. Full recovery
may take several more months. In some cases, the
injury is so severe that it requires tendon grafts and
muscle transfers. In rare cases, a severe injury is not
repairable, usually because the tendon has been torn
for too long a time.

Prevention
The best prevention is to avoid repetitive overhead
arm movements and to develop shoulder strength.
Resources
PERIODICALS

Hersch, Jonathan C. ‘‘Arthroscopically Assisted Mini-Open
Rotator Cuff Repairs.’’ The American Journal of Sports
Medicine May 2000: 301.
GALE ENCYCLOPEDIA OF MEDICINE

Group C rotavirus has been associated with rare cases
of diarrheal outbreaks in Japan and England. Groups
D through G have not been detected in humans.

Causes and symptoms

ORGANIZATIONS

American Academy of Orthopaedic Surgeons. 6300 N. River
Road, Rosemont, IL 60018. (847) 823-7186.
<http://www.aaos.org.>.
American Orthopaedic Society for Sports Medicine. 6300 N.
River Road, Ste. 200, Rosemont, IL 60018. (847)
292-4900. <http://www.sportsmed.org.>.
OTHER

WebMD. <http://www.my.webmd.com>.

Ken R. Wells

Rotavirus infections
Definition
Rotavirus is the major cause of diarrhea and
vomiting in young children worldwide. The infection
is highly contagious and may lead to severe dehydration (loss of body fluids) and even death. In the United
States, more than 50,000 children are hospitalized and
up to 125 die each year as a result of rotavirus
infection.

Description
Gastroenteritis, or inflammation of the stomach
and the intestine, is the second most common illness in
the United States, after the common cold. More than
one-third of such cases are caused by viruses. Many
different viruses can cause gastroenteritis, but the
most common ones are the rotavirus and the
Norwalk virus.
The name rotavirus comes from the Latin word
‘‘rota’’ for wheel and is given because the viruses have
a distinct wheel-like shape. Rotavirus infection is also
known as infantile diarrhea, or winter diarrhea,
because it mainly targets infants and young children.
The outbreaks are usually in the cooler months of
winter.
The virus is classified into different groups
(Group A through group G), depending on the type
of protein marker (antigen) that is present on its surface. The diarrheal infection of children is caused by
the Group A rotaviruses. Group B rotaviruses have
caused major epidemics of adult diarrhea in China.
GALE ENCYCLOPEDIA OF MEDICINE

The main symptoms of the rotavirus infection are
fever, stomach cramps, vomiting, and diarrhea (this
could lead to severe dehydration). The symptoms last
anywhere from four to six days. If a child has dry lips
and tongue, dry skin, sunken eyes, and wets fewer than
six diapers a day, it is a sign of dehydration and a
physician needs to be notified. Because of the excellence of healthcare in this country, rotavirus is rarely
fatal to American children. However, it causes deaths
of up to a million children in the third world countries,
every year.
The virus is usually spread by the ‘‘fecal-oral
route.’’ In other words, a child can catch a rotavirus
infection if she puts her finger in her mouth after
touching toys or things that have been contaminated
by the stool of another infected child. This usually
happens when children do not wash their hands after
using the toilet, or before eating food.
The viruses can also spread by way of contaminated food and drinking water. Infected food handlers
who prepare salads, sandwiches, and other foods that
require no cooking can spread the disease. Generally,
symptoms appear within 4–48 hours after exposure to
the contaminated food or water.
Children between the ages of six months and two
years, especially in a daycare setting, are the most
susceptible to this infection. Breastfed babies may be
less likely to become infected, because breast milk
contains antibodies (proteins produced by the white
blood cells of the immune system) that fight the illness.
Nearly every child by the age of four has been infected
by this virus, and has rotavirus antibodies in their
body. The disease also targets the elderly and people
who have weak immune systems.
Children who have been infected once can be
infected again. However, second infections are less
severe than the first infections. By the time a child
has had two infections, the chances of subsequent
severe infection is remote.

Diagnosis
The rotavirus infection is diagnosed by identifying
the virus in the patient’s stool. This is done using
electron microscopy. Immunological tests such as
ELISA (Enzyme-linked immunosorbent assay) are
3259

Rotavirus infections

Huie, Gordon, and Peter D. McCann. ‘‘The Shoulder Exam
and Diagnosing Rotator Cuff Injuries.’’ Physician
Assistant April 1999: 53.
Murrell, George A. C., and Judie R. Walton. ‘‘Diagnosis of
Rotator Cuff Tears.’’ The Lancet March 10, 2001: 769.

Roundworm infections

Vaccines that prevent rotavirus in young children
have been tested in nationwide trials. Researchers
report that the vaccines appear to prevent the infection
in 80% of the tested children. The vaccine is intended
to be given orally (by mouth) at two, four, and six
months of age. The only side effect of the vaccine is a
low-grade fever in a small percentage of the children,
three to four days after the vaccination. Within the
next few years, a rotavirus vaccine may become part
of every child’s immunization schedule.
Resources
BOOKS
Rotaviruses are probably the most common viruses to infect
humans and animals. These viruses are associated with gastroenteritis and diarrhea in humans and other animals.
(Photograph by Dr. Linda Stannard, Photo Researchers, Inc.
Reproduced by permission.)

Fauci, Anthony S., et al., editors. Harrison’s Principles of
Internal Medicine. New York: McGraw-Hill, 1997.

Lata Cherath, PhD

also widely used for diagnosis, and several commercial
kits are available.

Treatment
‘‘Oral rehydration therapy,’’ or drinking enough
fluids to replace those lost through bowel movements
and vomiting, is the primary aim of the treatment.
Electrolyte and fluid replacement solutions are available over the counter in food and drug stores.
Dehydration is one of the greatest dangers for infants
and young children. If the diarrhea becomes severe, it
may be necessary to hospitalize the patient so that
fluids can be administered intravenously.
Anti-diarrheal medication should not be given to
children unless directed to do so by the physician.
Antibiotic therapy is not useful in viral illness.
Specific drugs for the virus are not available.

Roundworm infections
Definition
Roundworm infections are diseases of the digestive tract and other organ systems caused by nematodes. Nematodes are parasitic worms with long,
cylindrical bodies.

Description
Roundworm infections are widespread throughout the world, with some regional differences.
Ascariasis and trichuriasis are more common in
warm, moist climates where people use human or
animal feces for fertilizer. Anisakiasis is most common
in countries where raw or pickled fish or squid is a
popular food item.

Prognosis
Most of the infections resolve spontaneously.
Dehydration due to severe diarrhea is one of the
major complications.

Prevention
The best way to prevent the disease is by proper
food handling and thorough hand washing, after using
the toilet and whenever hands are soiled. In child care
centers and hospital settings, the staff should be educated about personal and environmental hygiene. All
dirty diapers should be regarded as infectious and
disposed of in a sanitary manner.
3260

Causes and symptoms
The causes and symptoms of roundworm infection vary according to the species. Humans acquire
most types of roundworm infection from contaminated food or by touching the mouth with unwashed
hands.
Anisakiasis
Anisakiasis is caused by anisakid roundworms.
Humans are not the primary host for these parasites.
Anisakid roundworms infest whales, seals, and dolphins; crabs then ingest roundworm eggs from the
GALE ENCYCLOPEDIA OF MEDICINE

In humans, anisakiasis can produce a severe syndrome that affects the stomach and intestines, or a
mild chronic disease that may last for weeks or years.
In acute anisakiasis, symptoms begin within one to
seven hours after the patient eats infected seafood.
Patients are often violently sick, with nausea, vomiting,
diarrhea, and severe abdominal pain that may resemble appendicitis. In chronic anisakiasis, the patient has
milder forms of stomach or intestinal irritation that
resemble stomach ulcers or irritable bowel syndrome.
In some cases, the acute form of the disease is followed
by chronic infestation.
Ascariasis
Ascariasis, which is caused by Ascaris lumbricoides, is one of the most widespread parasitic infections in humans, affecting over 1.3 billion people
worldwide. Ascarid roundworms cause a larger burden on the human host than any other parasite; adult
worms can grow as long as 12 or 14 inches, and release
200,000 eggs per day. The eggs infect people who eat
unwashed vegetables from contaminated soil or touch
their mouths with unwashed hands. Once inside the
digestive tract, the eggs release larvae that penetrate
the intestinal wall and migrate to the lungs through
the liver and the bloodstream. After about 10 days
in the lungs, the larvae migrate further into the
patient’s upper lung passages and airway, where they
are swallowed. When they return to the intestine, they
mature into adults and reproduce. The time period
from the beginning of the infection to egg production
is 60–75 days.
The first symptoms of infection may occur when
the larvae reach the lungs. The patient may develop
chest pain, coughing, difficulty breathing, and inflammation of the lungs. In some cases, the patient’s sputum is streaked with blood. This phase of the disease is
sometimes called Loeffler’s syndrome. It is marked by
an accumulation of parasites in the lung tissue and by
eosinophilia (an abnormal increase in the number of a
specific type of white blood cell). The intestinal phase
of ascariasis is marked by stomach pain, cramping,
nausea, and intestinal blockage in severe cases.
GALE ENCYCLOPEDIA OF MEDICINE

Toxocariasis
Toxocariasis is sometimes called visceral larva
migrans (VLM) because the larval form of the organism hatches inside the intestines and migrates throughout the body to other organs (viscera). The disease is
caused by Toxocara canis and T. cati, which live within
the intestines of dogs and cats. Most human patients
are children between the ages of two and four years,
who become infected after playing in sandboxes or soil
contaminated by pet feces, although adults are also
susceptible. The eggs can survive in soil for as long as
seven years.
The organism’s eggs hatch inside the human intestine and release larvae that are carried in the bloodstream to all parts of the body, including the eyes,
liver, lungs, heart, and brain. The patient usually has
a fever, with coughing or wheezing and a swollen liver.
Some patients develop skin rashes and inflammation
of the lungs. The larvae may survive inside the body
for months, producing allergic reactions and small
granulomas, which are tissue swellings or growths
produced in response to inflammation. Infection of
the eye can produce ocular larva migrans (OLM),
which is the first symptom of toxocariasis in some
patients.
Trichuriasis
Trichuriasis, caused by Trichuris trichiura, is
sometimes called whipworm because the organism
has a long, slender, whiplike front end. The adult
worm is slightly less than an inch long. Trichuriasis is
most common in warm, humid climates, including the
southeastern United States. The number of people
with trichuriasis may be as high as 800 million
worldwide.
Whipworm larvae hatch from swallowed eggs in
the small intestine and move on to the upper part of
the large intestine, where they attach themselves to the
lining. The adult worms produce eggs that are passed
in the feces and mature in the soil. Patients with mild
infections may have few or no symptoms. In cases of
heavy infestation, the patient may have abdominal
cramps and other symptoms resembling amebic dysentery. In children, severe trichuriasis may cause anemia and developmental retardation.

Diagnosis
Since the first symptoms of roundworm infection
are common to a number of illnesses, a doctor is most
likely to consider the possibility of a parasitic disease on
the basis of the patient’s history–especially in children.
3261

Roundworm infections

feces of these animals. In the crabs, the eggs hatch into
larvae that can infect fish. The larvae enter the muscles
of marine animals further up the food chain, including
squid, mackerel, herring, cod, salmon, tuna, and halibut. Humans become accidental hosts when they eat
raw or undercooked fish containing anisakid larvae.
The larvae attach themselves to the tissues lining the
stomach and intestine, and eventually die inside the
inflamed tissue.

Roundworm infections

The definite diagnosis is based on the results of stool or
tissue tests. In trichuriasis, adult worms may also be
visible in the lining of the patient’s rectum. In ascariasis,
adult worms may appear in the patient’s feces or vomit;
they can also be detected by x ray and ultrasound. In
toxocariasis, larvae are sometimes found in tissue samples taken from a granuloma. If a patient with toxocariasis develops OLM, it is important to obtain a
granuloma sample in order to distinguish between
OLM and retinoblastoma (a type of eye tumor).
Anisakiasis is one of two roundworm infections
that cannot be diagnosed from stool specimens.
Instead, the diagnosis is made by x rays of the patient’s
stomach and small intestine. The larvae may appear as
small threads when double contrast x rays are used. In
acute cases, the doctor may use an endoscope (an
instrument for examining the interior of a body cavity)
to look for or remove larvae.
Blood tests cannot be used to differentiate among
different types of roundworm infections, but the presence of eosinophilia can help to confirm the
diagnosis.
Patients with trichuriasis or ascariasis should be
examined for signs of infection by other roundworm
species; many patients are infected by several parasites
at the same time.

Treatment
Trichuriasis, ascariasis, and toxocariasis are treated with anthelminthic medications. These are drugs
that destroy roundworms either by paralyzing them or
by blocking them from feeding. Anthelminthic drugs
include pyrantel pamoate, piperazine, albendazole,
and mebendazole. Mebendazole cannot be given to
pregnant women because it may harm the fetus.
Treatment with anthelminthic drugs does not prevent
reinfection.
There is no drug treatment for anisakiasis; however, symptoms usually resolve in one to two weeks
when the larvae die. In some cases, the larvae are
removed with an endoscope or by surgery.
Patients with an intestinal obstruction caused by
ascariasis may be given nasogastric suction, followed
by anthelminthic drugs, in order to avoid surgery. If
suction fails, the worms must be removed surgically to
prevent intestinal rupture or blockage.

Prognosis
The prognosis for recovery from roundworm
infections is good for most patients. The severity of
3262

KEY TERMS
Eosinophilia—An abnormal increase in the number
of a specific type of white blood cell. Eosinophilia
is a characteristic of all types of roundworm
infections.
Granuloma—A tissue swelling produced in
response to inflammation. Granulomas are important in diagnosing toxocariasis.
Loeffler’s syndrome—The respiratory phase of
ascariasis, marked by inflammation of the lungs
and eosinophilia.
Nematode—A parasitic roundworm with a long,
cylindrical body.
Ocular larva migrans (OLM)—A syndrome associated with toxocariasis, in which the eye is
invaded by migrating larvae.
Visceral larva migrans (VLM)—Another name for
toxocariasis. The name is derived from the life
cycle of the organism.
Whipworm—Another name for trichuriasis. The
name comes from the organism’s long whiplike
front end.

infection, however, varies considerably from person to
person. Children are more likely to have heavy infestations and are also more likely to suffer from malabsorption and malnutrition than adults.
Ascariasis is the only roundworm infection with a
significant mortality rate. A. lumbricoides grows large
enough to perforate the bile or pancreatic ducts; in
addition, a mass of worms in the digestive tract can
cause rupture or blockage of the intestines. It is estimated that 20,000 children die every year from intestinal ascariasis.

Prevention
There are no effective vaccines against any of the
soil-transmitted roundworms, nor does infection confer immunity. Prevention of infection or reinfection
requires adequate hygiene and sanitation measures,
including regular and careful handwashing before eating or touching the mouth with the hands.
With respect to specific infections, anisakiasis can
be prevented by avoiding raw or improperly prepared
fish or squid. Trichuriasis, ascariasis, and toxocariasis
can be prevented by keeping children from playing in
soil contaminated by human or animal feces; by
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Goldsmith, Robert S. ‘‘Infectious Diseases: Protozoal &
Helminthic.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Routine urinalysis see Urinalysis
RSV see Respiratory syncytial virus infection
RTA see Renal tubular acidosis
RU-486 see Mifepristone

Although rubella is generally considered a childhood illness, people of any age who have not been
vaccinated or previously caught the disease can
become infected. Having rubella once or being immunized against rubella normally gives lifetime immunity. This is why vaccination is so effective in
reducing the number of rubella cases.
Women of childbearing age who do not have
immunity against rubella should be the most concerned
about getting the disease. Rubella infection during the
first three months of pregnancy can cause a woman to
miscarry or cause her baby to be born with birth
defects. Although it has been practically eradicated in
the United States, rubella is still common in less developed countries because of poor immunization penetration, creating a risk to susceptible travelers. Some
countries have chosen to target rubella vaccination to
females only and outbreaks in foreign-born males have
occurred on cruise ships and at U.S. summer camps.

Causes and symptoms

Rubella
Definition
Rubella is a highly contagious viral disease,
spread through contact with discharges from the
nose and throat of an infected person. Although
rubella causes only mild symptoms of low fever, swollen glands, joint pain, and a fine red rash in most
children and adults, it can have severe complications
for women in their first trimester of pregnancy. These
complications include severe birth defects or death of
the fetus.

Description
Rubella is also called German measles or threeday measles. This disease was once a common childhood illness, but its occurrence has been drastically
reduced since vaccine against rubella became available
in 1969. In the 20 years following the introduction of
the vaccine, reported rubella cases dropped 99.6%.
Only 229 cases of rubella were reported in the United
States in 1996.
Rubella is spread through contact with fluid droplets expelled from the nose or throat of an infected
person. A person infected with the rubella virus is
contagious for about seven days before any symptoms
appear and continues to be able to spread the disease
for about four days after the appearance of symptoms.
Rubella has an incubation period of 12–23 days.
GALE ENCYCLOPEDIA OF MEDICINE

Rubella is caused by the rubella virus (Rubivirus).
Symptoms are generally mild, and complications are
rare in anyone who is not pregnant.
The first visible sign of rubella is a fine red rash
that begins on the face and rapidly moves downward
to cover the whole body within 24 hours. The rash lasts
about three days, which is why rubella is sometimes
called the three-day measles. A low fever and swollen
glands, especially in the head (around the ears) and
neck, often accompany the rash. Joint pain and sometimes joint swelling can occur, more often in women. It
is quite common to get rubella and not show any
symptoms (subclinical infection).
Symptoms disappear within three to four days,
except for joint pain, which may linger for a week or
two. Most people recover fully with no complications.
However, severe complications may arise in the
unborn children of women who get rubella during
the first three months of their pregnancy. These babies
may be miscarried or stillborn. A high percentage are
born with birth defects. Birth defects are reported to
occur in 50% of women who contract the disease
during the first month of pregnancy, 20% of those
who contract it in the second month, and 10% of
those who contract it in the third month.
The most common birth defects resulting from
congenital rubella infection are eye defects such as
cataracts, glaucoma, and blindness; deafness; congenital heart defects; and mental retardation. Taken
together, these conditions are called congenital rubella
3263

Rubella

teaching children to wash their hands before eating;
and by having pets dewormed regularly by a
veterinarian.

Rubella

and IgM) or determine whether a person has immunity
to rubella (IgG only). The lack of antibodies indicates
that a person is susceptible to rubella.
All pregnant women should be tested for rubella
early in pregnancy, whether or not they have a history
of vaccination. If the woman lacks immunity, she is
counseled to avoid anyone with the disease and to be
vaccinated after giving birth.

Treatment
There is no drug treatment for rubella. Bed rest,
fluids, and acetaminophen for pain and temperatures
over 1028F (38.98C) are usually all that is necessary.
Babies born with suspected CRS are isolated and
cared for only by people who are sure they are immune
to rubella. Congenital heart defects are treated with
surgery.

Alternative treatment
Rather than vaccinating a healthy child against
rubella, many alternative practitioners recommend
allowing the child to contract the disease naturally at
the age of five or six years, since the immunity conferred by contracting the disease naturally lasts a lifetime. It is, however, difficult for a child to contract
rubella naturally when everyone around him or her
has been vaccinated.
A red rash is one characteristic of rubella, or German
measles, as seen on this man’s arm. (Custom Medical Stock
Photo. Reproduced by permission.)

syndrome (CRS). The risk of birth defects drops after
the first trimester, and by the 20th week, there are
rarely any complications.

Diagnosis
The rash caused by the rubella virus and the
accompanying symptoms are so similar to other viral
infections that it is impossible for a physician to make a
confirmed diagnosis on visual examination alone. The
only sure way to confirm a case of rubella is by isolating
the virus with a blood test or in a laboratory culture.
A blood test is done to check for rubella antibodies.
When the body is infected with the rubella virus, it
produces both immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to fight the infection.
Once IgG exists, it persists for a lifetime, but the special
IgM antibody usually wanes over six months. A blood
test can be used either to confirm a recent infection (IgG
3264

Ayurvedic practitioners recommend making the
patient comfortable and giving the patient ginger or
clove tea to hasten the progress of the disease.
Traditional Chinese medicine uses a similar approach.
Believing that inducing the skin rash associated with
rubella hastens the progress of the disease, traditional
Chinese practitioners prescribe herbs such as peppermint (Mentha piperita) and chai-hu (Bupleurum chinense). Cicada is often prescribed as well. Western
herbal remedies may be used to alleviate rubella symptoms. Distilled witch hazel (Hamamelis virginiana)
helps calm the itching associated with the skin rash
and an eyewash made from a filtered diffusion of eyebright (Euphrasia officinalis) can relieve eye discomfort.
Antiviral western herbal or Chinese remedies can be
used to assist the immune system in establishing equilibrium during the healing process. Depending on the
patient’s symptoms, among the remedies a homeopath
may prescribe are Belladonna,Pulsatilla, or Phytolacca.

Prognosis
Complications from rubella infection are rare in
children, pregnant women past the 20th week of
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (914) 4287100. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Tish Davidson, A.M.
A digitized image of rubella virus particles. (Custom Medical
Stock Photo. Reproduced by permission.)

KEY TERMS

Rubella test
Definition

Incubation period—The time it takes for a person
to become sick after being exposed to a disease.
Trimester—The first third or 13 weeks of pregnancy.

pregnancy, and other adults. For women in the first
trimester of pregnancy, there is a high likelihood of the
child being born with one or more birth defect.
Unborn children exposed to rubella early in pregnancy
are also more likely to be miscarried, stillborn, or have
a low birthweight. Although the symptoms of rubella
pass quickly for the mother, the consequences to the
unborn child can last a lifetime.

Prevention
Vaccination is the best way to prevent rubella and
is normally required by law for children entering
school. Rubella vaccine is usually given in conjunction
with measles and mumps vaccines in a shot referred to
as MMR (mumps, measles, and rubella). Children
receive one dose of MMR vaccine at 12-15 months
and another dose at four to six years.
Pregnant women should not be vaccinated, and
women who are not pregnant should avoid conceiving
for at least three months following vaccination. To
GALE ENCYCLOPEDIA OF MEDICINE

The rubella test is a routine blood test performed
as part of prenatal care of pregnant women. It is sometimes also used to screen women of childbearing age
before the first pregnancy.

Purpose
The test is given to evaluate whether a woman is
immune to rubella (German measles) as a result of
childhood exposure or immunization, or whether she
may be presently infected with the disease. The question of a current infection is particularly urgent for
pregnant women. Although the disease itself is not
serious in adults, it can cause miscarriage, stillbirth,
or damage to the fetus during the first trimester (three
months) of pregnancy. The rubella test is regarded as a
more reliable indication of the patient’s immune status
than her history, because reinfection with rubella is
possible even after immunization. The results of the
test may influence decisions to terminate a pregnancy.

Description
The rubella test belongs to a category of blood
tests called hemagglutination inhibition (HI) tests.
Hemagglutination refers to the clumping or clustering
of red blood cells caused by a disease antibody, virus,
3265

Rubella test

date, however, accidental rubella vaccinations during
pregnancy have not clearly been associated with the
same risk as the natural infection itself. Women may
be vaccinated while they are breastfeeding. People
whose immune systems are compromised, either by
the use of drugs such as steroids or by disease, should
discuss possible complications with their doctor before
being vaccinated.

Rubella test

or certain other substances. Inhibition refers to interference with the clumping process. The presence of
rubella antibodies inhibits the cell clumping caused
by the rubella virus. Thus, the addition of the virus
to a sample of the patient’s blood allows a doctor to
determine the presence and concentration of rubella
antibodies and the patient’s immunity to the disease.
When a person is infected with the rubella virus, the
body produces both immunoglobulin G (IgG) and
immunoglobulin M (IgM) antibodies to fight the infection. Once IgG exists, it persists for a lifetime, but the
special IgM antibody usually wanes over six months.
The rubella test can either confirm that a recent infection
has occurred (both IgG and IgM are present) or that a
patient has immunity to rubella (IgG only is present).
When the test is performed to confirm the diagnosis of rubella in a woman already pregnant, two
blood samples are drawn. One is drawn during the
acute phase of the illness about three days after the
rash breaks out, and the second is drawn during the
convalescent phase about three weeks later. The specimens are then tested simultaneously by a single
laboratory. Alternatively, a pregnant woman with a
rash suspected to be rubella can be tested for IgM
antibody. If the test shows that IgM antibody is present, then a recent rubella infection has occurred.
Because there have been cases of children born
with rubella syndrome even though the mother’s
blood test indicated that she was sufficiently immune
to rubella, some researchers are presently recommending a second test, known as a synthetic peptide
enzyme-linked immunosorbent assay (ELISA). This
test screens for the presence of rubella virus neutralizing (RVN) antibodies in the mother’s blood.

Normal results
If the patient has been successfully immunized
against rubella or has had the disease, the HI antibody
titer (concentration) will be greater than 1:10–1:20.
The red blood cells will fail to clump when the rubella
virus is added to the blood serum.
In the case of paired testing for pregnant women,
a fourfold rise in antibody titer between the first and
second blood samples indicates the suspicious rash
was caused by rubella. The alternative test for IgM
antibody confirms recent rubella infection if IgM is
found in the patient’s blood.

Abnormal results
If the patient has little or no immunity to rubella,
her HI antibody titer will be 1:8 or less. Women
3266

KEY TERMS
Antibody—A protein molecule produced by the
immune system that is specific to a virus, such as
the rubella virus. The antibody combines with the
virus and disables it.
Hemagglutination—The clumping or clustering of
red blood cells caused by certain viruses, antibodies, or other substances.
Inhibition—Restraint of or interference with a biological process, such as the clumping of blood cells.
Titer—The concentration of a substance in a given
sample of blood or other tissue fluid.

without immunity should receive immunization
against rubella provided that they avoid pregnancy
for a period of three months following immunization.
Women with disease of the immune system or who are
taking corticosteroid medications should receive
immune serum globulin rather than rubella vaccine
to prevent infection.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Childhood Infections: Viral Infections.’’ In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PERIODICALS

Andrews, J. I. ‘‘Diagnosis of Fetal Infections’’ Current
Opinion in Obstetrics and Gynecology 16 (April 2004):
163–166.
Giessauf, A., T. Letschka, G. Walder, et al. ‘‘A Synthetic
Peptide ELISA for the Screening of Rubella Virus
Neutralizing Antibodies in Order to Ascertain
Immunity.’’ Journal of Immunological Methods 287
(April 2004): 1–11.
ORGANIZATIONS

American Academy of Family Physicians (AAFP). 11400
Tomahawk Creek Parkway, Leawood, KS 66211-2672.
(800) 274-2237 or (913) 906-6000.
<http://www.aafp.org>.

Rebecca J. Frey, PhD

Rubeola see Measles
Ruptured disk see Herniated disk
RVT see Renal vein thrombosis
GALE ENCYCLOPEDIA OF MEDICINE

S
Sacroiliac disease
Definition
Sacroiliac disease is high-impact trauma to the
sacroiliac joint that can cause death, or bone, and
nerve damage.

Description
The sacroiliac joint is a strong, weight bearing
synovial joint between the ilium and sacrum bones of
the pelvis. The bones are held in place and allowed
limited movements by a system of sacroiliac ligaments.
Relaxation of this and other joints and ligaments is
important during pregnancy and is accomplished by a
special hormone called relaxin. Usually the sacroiliac
is damaged by high-impact injuries. These injuries
may be life threatening and mortality is approximately
20% if neighboring structures are also damaged.
Injuries to this area often includes neurological deficits. Dislocation and nerve damage are frequently
missed in the diagnosis.

Causes and symptoms
The primary cause of dislocations, fractures, and
accompanying damage is usually a traumatic accident.
Patients receiving such injuries require emergency
medical attention. There may be severe blood loss
due to breakage of large bones and resuscitative measures may be required for stabilization.

Diagnosis
The diagnosis can be difficult since nerve
damage can mimic other conditions with similar
symptoms (i.e., low back pain in persons with sciatica). Additionally imaging studies and physical
examination maneuvers will miss the diagnosis. The
definitive method for diagnosing sacroiliac
GALE ENCYCLOPEDIA OF MEDICINE

pathology would be injection of local anesthetic in
the correct area of the affected sacroiliac joint. This
procedure is usually performed using advance
guidance systems (CT or fluoroscopic assisted guidance). If the pain is relieved by anesthetic injection,
then the diagnosis is confirmed. There are three
typical patterns of pain: pain directly over the joint,
pain in the groin extending down the affected leg
that can mimic the signs associated with a herniated
lumbar disc, and pain widely dispersed in the
affected leg.

Treatment
Treatment initially can include emergency interventions, but usually is conservative. Treatment
includes physical therapy, manipulation, and medications for pain control. In some cases a sacroiliac belt
can help with symptoms. In sacroiliac joint disease
that has already progressed and is chronic and severe,
corrective joint fusion may be indicated.

Prognosis
Outcome is variable and takes into account the
extent of injuries, early diagnosis, and responsiveness
to conservative treatment.

Prevention
There is no known prevention since the disease is
secondary to an accident.
Resources
BOOKS

Goetz, Christopher G., et al, editors. Textbook of
Clinical Neurology. 1st ed. W. B. Saunders Company,
1999.
Ruddy, Shaun, et al, editors. Kelly’s Textbook of
Rheumatology. 6th ed. W. B. Saunders Company, 2001.
3267

St. John’s wort

KEY TERMS
Herniated disk—A protrusion in a disk located in
the spinal column.
Ligament—Fibrous tissue which connect bones.
Synovial joint—A joint that allows for bone
movement.

topped clusters atop the stalks in mid-summer, around
the time of the summer solstice. St. John’s wort, sometimes called devil’s flight or grace of God, was believed
to have magical properties to ward off evil spirits. It’s
generic name hypericum is derived from a Greek word
meaning ‘‘over an apparition.’’ The herb was traditionally gathered on mid-summer’s eve, June 23. This date
was later christianized as the eve of the feast day of
St. John the Baptist. This folk custom gave the plant its
popular name. The Anglo-Saxon word wort means
medicinal herb.

OTHER

American Academy of Orthopaedic Surgeons.
<http://www.aaos.org>.

Laith Farid Gulli, M.D.

SAD see Seasonal affective disorder
St. Anthony’s fire see Erysipelas

St. John’s wort
Definition
Hypericum perforatum is the most medicinally
important species of the Hypericum genus, commonly
known as St. John’s wort. There are as many as 400
species in the genus, which is part of the Guttiferae
family. Native to Europe, St. John’s wort is found
throughout the world. It thrives in sunny fields, open
woods, and gravelly roadsides. Early colonists
brought this valuable medicinal to North America,
and the plant has become naturalized in the eastern
United States and California, as well as in Australia,
New Zealand, eastern Asia, and South America.
The entire plant, particularly the round, black seed,
exudes a slight, turpentine-like odor. The woody,
branched root spreads from the base with runners
that produce numerous stalks. The simple, dark green
leaves are veined and grow in opposite, oblong-obvate
pairs on round, branching stalks that reach 3 ft (91.4
cm) high. Tiny holes, visible when the leaf is held to the
light, are actually transparent oil glands containing the
chemical photo sensitizer known as hypericin. These
characteristic holes inspired the species name, perforatum, Latin for perforated. The bright yellow, starshaped flowers, often clustered in a trio, have five
petals. Each blossom has many showy stamens. Black
dots along the margins of the blossom contain more of
the red-pigmented chemical hypericin. The herb is also
useful as a dye. The flowers bloom in branching, flat3268

Purpose
St. John’s wort has been known for its numerous
medicinal properties as far back as Roman times. It
was a valued remedy on the Roman battlefields where
it was used to promote healing from trauma and
inflammation. The herb is vulnerary and can speed
the healing of wounds, bruises, ulcers, and burns. It is
popularly used as a nervine for its calming effect,
easing tension and anxiety, relieving mild depression,
and soothing emotions during menopause. The bittersweet herb is licensed in Germany for use in cases of
mild depression, anxiety, and sleeplessness. It is useful
in circumstances of nerve injury and trauma, and has
been used to speed healing after brain surgery. Its
antispasmodic properties can ease uterine cramping
and menstrual difficulties. St. John’s wort acts medicinally as an astringent, and may also be used as an
expectorant. The hypericin in St. John’s wort possesses anti-viral properties that may be active in combating certain cancers, including many brain cancers.
An infusion of the plant, taken as a tea, has been
helpful in treating night-time incontinence in children.
The oil, taken internally, has been used to treat colic,
intestinal worms, and abdominal pain. The medicinal
parts of St. John’s wort are the fresh leaves and flowers. This valuable remedy has been extensively tested
in West Germany, and is dispensed throughout
Germany as a popular medicine called, Johnniskraut.
Commercially prepared extracts are commonly standardized to 0.3% hypericin.
Clinical studies
A 1988 study at New York University found the
antiviral properties in hypericin, a chemical component of Hypericum, to be useful in combating the virus
that causes AIDS. Additional studies are under way
through the Federal Drug Administration (FDA) to
determine the effectiveness of the herb as a treatment
for AIDS. Hypericin extract has also been reported to
inhibit a form of leukemia that sometimes occurs after
radiation therapy. Numerous clinical studies have
GALE ENCYCLOPEDIA OF MEDICINE

St. John’s wort

found hypericum preparations to have an antidepressive effect when used in standardized extracts for treatment of mild depression. Clinical trials continue with
this important herbal anti-depressant, particularly in
view of its relative lack of undesirable side effects in
humans.

Preparations
An oil extract can be purchased commercially or
prepared by combining fresh flowers and leaves of
St. John’s wort in a glass jar and sunflower or olive
oil. Seal the container with an airtight lid and leave on
a sunny windowsill for four to six weeks, shaking
daily. The oil will absorb the red pigment. Strain
through muslin or cheesecloth, and store in a dark
container. The medicinal oil will maintain its potency
for two years or more. The oil of St. John’s wort has
been known in folk culture as ‘‘Oil of Jesus.’’ This oil
makes a good rub for painful joints, varicose veins,
muscle strain, arthritis, and rheumatism. Used in a
compress it can help to heal wounds and inflammation, and relieve the pain of deep bruising.
An infusion is made by pouring one pint of boiling
water over 1 oz (28 g) of dried herb, or 2 oz (57 g) of
fresh, minced flower and leaf. Steep in a glass or
enamel pot for five to 10 minutes. Strain and cover.
Drink the tea warm. A general dose is one cupful, up
to three times daily.
Capsule: Dry the leaves and flowers and grind
with mortar and pestle into a fine powder. Place in
gelatin capsules. The potency of the herb varies with
the soil, climate and harvesting conditions of the plant.
A standardized extract of 0.3% hypericin extract,
commercially prepared from a reputable source, is
more likely to yield reliable results. Standard dosage
is up to three 300 mg capsules of 0.3% standardized
extract daily.
A tincture is prepared by combining one part fresh
herb to three parts alcohol (50% alcohol/water solution) in glass container. Set aside in dark place, shaking the mixture daily for two weeks. Strain through
muslin or cheesecloth, and store in dark bottle. The
tincture should maintain potency for two years.
Standard dosage, unless otherwise prescribed, is
0.24–1 tsp added to 8 oz (237 ml) of water, up to
three times daily.
A salve is made by warming 2 oz (59 ml)of prepared oil extract in double boiler. Once warmed, 1 oz
(28 g) of grated beeswax is added and mixed until
melted. Pour into a glass jar and cool. The salve can
be stored for up to one year. The remedy keeps best if
refrigerated after preparation. The salve is useful in
GALE ENCYCLOPEDIA OF MEDICINE

St. John’s wort flowers. (Photo Researchers, Inc. Reproduced
by permission.)

treating burns, wounds, and soothing painful muscles.
It is also a good skin softener. St. John’s wort salve
may be prepared in combination with calendula
extract (Calendula officinalis) for application on
bruises.

Precautions
Consult a physician prior to use. Pregnant or
lactating women should not use the herb. Individuals
taking prescribed psychotropic medications classified
as selective serotonin reuptake inhibitors, or SSRI, such
as Prozac, should not simultaneously use St. John’s
wort. Many herbalists also discourage use of St. John’s
wort by individuals taking any other anti-depressant
medication.
Cattlemen dislike the shrub because there have
been some reports of toxicity to livestock that overgraze in fields abundant with the wild herb. Toxic
3269

Salivary gland scan

KEY TERMS

Salivary gland scan

Antispasmodic—Relieves mild cramping or muscle spasm.
Expectorant—Promotes the discharge of mucus
from respiratory system.
Nervine—Soothes and calms the nervous system.
Vulnerary—Heals wounds, bruises, sprains, and
ulcers.

Definition
A salivary gland scan is a nuclear medicine test
that examines the uptake and secretion in the salivary
glands of a radioactively labeled marker substance.
The pattern of uptake and secretion shows if these
glands are functioning normally.

Purpose
effects in livestock include reports of edema of the ears,
eyelids, and the face due to photosensitization after
ingestion of the herb. Exposure to sunlight activates
the hypercin in the plant. Adverse effects have been
reported in horses, sheep, and swine and include staggering, and blistering and peeling of the skin. Toxicity
is greater in smaller mammals, such as rabbits.

Side effects
When used either internally or externally, the herb
may cause photo-dermatitis in humans with fair or
sensitive skin when exposed to sun light or other ultraviolet light source. There have been some reports of
changes in lactation in some nursing women taking the
hypericum extract. Changes in the nutritional quality
and flavor of the milk, and reduction or cessation of
lactation have also been reported. It can also cause
headaches, stiff neck, nausea and vomiting, and high
blood pressure.

Interactions
St. John’s wort can interact with amphetamines,
asthma inhalants, decongestants, diet pills, narcotics,
and amino acid tryptophan and tyrosine, as well as
certain foods. Reactions range from nausea to
increased high blood pressure. Consult a practitioner
prior to using St. John’s wort.
Resources
ORGANIZATIONS

American Botanical Council. PO Box 201660, Austin, TX
78720-1660.
OTHER

Precautions
Salivary gland scans are a safe and effective way to
diagnose problems associated with dry mouth. The
level of radioactivity in the marker substance is low
and poses no threat to health. The only people who
should not undergo this test are pregnant women.
Other recent nuclear medicine tests may affect the
results of this scan. It may be necessary to wait until
earlier radiopharmaceuticals have been cleared from
the body before undergoing this scan.

Description
A salivary gland scan, also called a parotid gland
scan, is a noninvasive test. The patient is positioned
under a gamma scintillation camera that detects radiation. The patient then is injected with a low-level
radioactive marker, usually technetium-99m or technetium pertechnetate.
Immediately after the injection, imaging begins.
For accurate results, the patient must stay still during
imaging. After several images, the patient is given lemon
drop candies to suck on, which stimulate the salivary
glands. Another set of images is made for comparison
purposes. The entire process takes about ten minutes
for the injection and 30–45 minutes for the scan.

Preparation

Herb Research Foundation. <http://www.herbs.org>.

Clare Hanrahan

St. Vitus’ dance see Sydenham’s chorea
3270

A salivary gland scan is done to help diagnose the
cause of dry mouth. It is a test that is done when
Sjogren’s syndrome, salivary duct obstruction, asymmetric hypertrophy, or growths such as Warthin’s
tumors are suspected.

No special preparations are needed for this test. It
is not necessary to fast or to restrict medications
before testing. Any blood that needs to be drawn for
other tests should be taken before the radiopharmaceutical is injected.
GALE ENCYCLOPEDIA OF MEDICINE

Hypertrophy—Overgrowth of tissue not due to a
tumor.
Parotid gland—The salivary gland that lies below
and in front of each ear.
Radiopharmaceutical—A radioactive pharmaceutical or chemical (usually radioactive iodine or
cobalt) used for diagnostic or therapeutic purposes.
Sjögren’s syndrome—A disease often associated
with rheumatoid arthritis, that causes dry mouth,
lesions on the skin, and enlargement of the parotid
glands. It is often seen in menopausal women.
Technetium—A synthetic element used in nuclear
medicine; it is obtained from the fission of uranium.

Baur, D. A., T. F. Heston, and J. I. Helman. ‘‘Nuclear
Medicine in Oral and Maxillofacial Diagnosis: A
Review for the Practicing Dental Professional.’’
Journal of Contemporary Dental Practice 5
(February 15, 2004): 94–104.
Chae, S. W., J. H. Sohn, H. S. Shin, et al.‘‘Unilateral,
Multicentric Warthin’s Tumor Mimicking a Tumor
Metastatic to a Lymph Node. A Case Report.’’ Acta
Cytologica 48 (March-April 2004): 229 –233.
ORGANIZATIONS

Society of Nuclear Medicine (SNM). 1850 Samuel Morse
Drive, Reston, VA 20190-5316. (703) 708-9000. Fax:
(703) 708-9015. <http://www.snm.org>.
OTHER

‘‘Salivary Gland Scan.’’ HealthGate Page.
<http://www3.healthgate.com>.

Warthin’s tumor—A benign tumor of the parotid
gland.

Tish Davidson, AM
Rebecca J. Frey, PhD

Aftercare
Patients can
immediately.

return

to

normal

activities

Salivary gland tumors
Definition

Risks
A salivary gland scan is a safe test. The only risk is
to the fetus of a pregnant woman. Women who are
pregnant should discuss the risks and benefits of this
procedure with their doctor.

Normal results
Normally functioning salivary glands take up the
radiopharmaceutical then secrete it when stimulated
by the lemon drops.

Abnormal results
Abnormally functioning salivary glands fail to
exhibit a normal uptake and secretion pattern. This
test does not differentiate between benign and malignant lesions.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disorders of the Oral Region: Neoplasms.’’ Section 9,
Chapter 105 In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

GALE ENCYCLOPEDIA OF MEDICINE

A salivary gland tumor is an uncontrolled growth
of cells that originates in one of the many saliva-producing glands in the mouth.

Description
The tongue, cheeks, and palate (the hard and soft
areas at the roof of the mouth) contain many glands
that produce saliva. In saliva there are enzymes, or
catalysts, that begin the breakdown (digestion) of food
while it is still in the mouth. The glands are called
salivary glands because of their function.
There are three big pairs of salivary glands in
addition to many smaller ones. The parotid glands,
submandibular glands and sublingual glands are the
large, paired salivary glands. The parotids are located
inside the cheeks, one below each ear. The submandibular glands are located on the floor of the mouth,
with one on the inner side of each part of the lower
jaw, or mandible. The sublingual glands are also in the
floor of the mouth, but they are under the tongue.
The parotids are the salivary glands most often
affected by tumors. Yet most of the tumors that grow
in the parotid glands are benign, or not cancerous.
Approximately 8 out of 10 salivary tumors diagnosed
are in a parotid gland. One in 10 diagnosed is in a
3271

Salivary gland tumors

PERIODICALS

KEY TERMS

Salivary gland tumors

a cause. Ionizing radiation, particularly gamma radiation, is a factor that contributes to tumor development.
So is radiation therapy. Adults who received radiation
therapy for enlarged adenoids or tonsils when they were
children are at greater risk for salivary gland tumors.
Another reported risk factor is an association
between wood dust inhalation and adenocarcinoma
of the minor salivary glands of the nose and paranasal
sinuses. There is also evidence that people infected
with herpes viruses may be at greater risk for salivary
gland tumors. And individuals infected with human
immunodeficiency virus (HIV) have more salivary
gland disease in general, and may be at greater risk
for salivary gland tumors.
Although there has been speculation that the electromagnetic fields generated by cell phones increase
the risk of salivary gland tumors, a recent study done
in Denmark has concluded that the use of cell phones,
pagers, and similar devices is not a risk factor.
A salivary gland with a tumor. (Illustration by Argosy Inc.)

submandibular gland. The remaining 10% are diagnosed in other salivary glands.
In general, glands more likely to show tumor
growth are also glands least likely to show malignant
tumor growth. Thus, although tumors of the sublingual glands are rare, almost all of them are malignant.
In contrast, about one in four tumors of the parotid
glands is malignant.
Cancers of the salivary glands begin to grow in
epithelial cells, or the flat cells that cover body surfaces. Thus, they are called carcinomas, cancers that
by definition begin in epithelial cells.

Demographics
Cancers in the mouth account for fewer than 2%
of all cases of cancer and about 1.5% of cancer deaths.
About 7% of all cancers diagnosed in the head and
neck region are diagnosed in a salivary gland. Men
and women are at equal risk.
Mortality from salivary gland tumors in the
United States is higher among male African
Americans below the age of 50 than among older
workers of any race or either sex. The reasons for
these findings are not clear as of early 2004.

There seems to be some link between breast cancer
and salivary gland tumors. Women with breast cancer
are more likely to be diagnosed with salivary gland
tumors. Also linked to salivary gland tumors is alcohol
use, exposure to sunlight (ultraviolet radiation) and
hair dye use. There is evidence that people infected
with herpes viruses may be at greater risk for salivary
gland tumors. Individuals infected with human immunodeficiency virus (HIV) have more salivary gland
disease in general, and may be at greater risk for
salivary gland tumors.
Symptoms are often absent until the tumor is large
or has metastasized (spread to other sites). In many
cases, the tumor is first discovered by the patient’s
dentist. During regular dental examinations, the dentist looks for masses on the palate or under the tongue
or in the cheeks, and such checkups are a good way to
detect tumors early. Some symptoms are:


a lump or mass in the mouth



swelling in the face



pain in the jaw or the side of the face



difficulty swallowing



difficulty breathing



difficulty speaking

Diagnosis
Causes and symptoms
When survivors of the 1945 atomic bombings of
Nagasaki and Hiroshima began to develop salivary
gland tumors at a high rate, radiation was suspected as
3272

A tissue sample will be taken for study via a
biopsy. Usually an incision is necessary to take the
tissue sample. Sometimes it is possible to take a tissue
sample with a needle.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
To assess the stage of growth of a salivary gland
tumor, many features are examined, including how big
it is and the type of abnormal cell growth. Analysis of
the types of abnormal cell growth in tissue is so specific
that many salivary gland tumors are given unique
names.
In stage I cancer the tumor is less than one inch in
size and it has not spread. Stage II salivary gland
cancers are larger than one inch and smaller than
two and one-half inches, but they have not spread.
Stage III cancers are smaller than one inch, but they
have spread to a lymph node. Stage IV cancers have
spread to adjacent sites in the head, which may include
the base of the skull and nearby nerves, or they are
larger than two and one-half inches and have invaded
a lymph node.
Surgical removal (excision) of the tumor is the
most common treatment. Chemotherapy and radiation therapy may be part of the treatment, particularly if the cancer has metastasized, or spread to
other sites; chemotherapy of salivary gland cancers,
however, does not appear to extend survival or
improve the patient’s quality of life. Because there
are many nerves and blood vessels near the three
major pairs of salivary glands, particularly the
parotids, the surgery can be quite complicated. A
complex surgery is especially true if the tumor has
spread.
A promising form of treatment for patients at
high risk of tumor recurrence in the salivary glands
near the base of the skull is gamma knife surgery.
Used as a booster treatment following standard neutron radiotherapy, gamma knife surgery appears to
be well tolerated by the patients and to have minimal
side effects.

Alternative treatment
Any technique, such as yoga, meditation or biofeedback, that helps a patient cope with anxiety over
the condition and discomfort from treatment is useful
and should be explored as an option.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Adenoids—Common name for the pharyngeal tonsils, which are lymph masses in the wall of the air
passageway (pharynx) just behind the nose.
Biopsy—Tissue sample is taken from the body for
examination.
Computed tomography (CT)—X rays are aimed at
slices of the body (by rotating equipment) and
results are assembled with a computer to give a
three-dimensional picture of a structure.
Lymph—Tissue that is part of the lymphatic system,
the system that collects and returns fluid to the blood
vessels and produces substances that fight infection.
Magnetic resonance imaging (MRI)—Magnetic
fields and radio frequency waves are used to take
pictures of the inside of the body.
Tonsils—Common name for the palatine tonsils,
which are lymph masses in the back of the mouth,
on either side of the tongue.

Prognosis
Tumors in small salivary glands that are localized
can usually be removed without much difficulty. The
outlook for survival once the tumor is removed is very
good if it has not metastasized.
For parotid cancers, the five-year survival rate is
more than 85% whether or not a lymph node is involved
at diagnosis. Ten-year survival rate is just under 50%.
Most early stage salivary gland tumors are
removed, and they do not return. Those that do
return, or recur, are the most troublesome and reduce
the chance an individual will remain cancer-free.

Prevention
Minimizing intake of beverages containing alcohol may be important. Avoiding unnecessary exposure
of the head to radiation and to sunlight may also be
considered preventative. Anything that reduces the
risk of contracting a sexually transmitted disease,
such as the use of condoms, also may lower the risk
of salivary gland cancer.
A salivary gland with a tumor.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disorders of the Oral Region: Neoplasms.’’ Section 9,
3273

Salivary gland tumors

Magnetic resonance imaging (MRI) and computed tomography (CT) scans are also used to evaluate the tumor. They help determine whether the
cancer has spread to sites adjacent to the salivary
gland where it is found. MRI offers a good way to
examine the tonsils and the back of the tongue, which
are soft tissues. CT is tapped as a way of studying the
jaw, which is bone.

Salmonella food poisoning

Chapter 105 In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

transmit this illness, most people become infected by
ingesting foods contaminated with significant
amounts of Salmonella.

PERIODICALS

Day, T. A., J. Deveikis, M. B. Gillespie, et al. ‘‘Salivary
Gland Neoplasms.’’ Current Treatment Options in
Oncology 5 (February 2004): 11–26.
Douglas, J. G., D. L. Silbergeld, and G. E. Laramore.
‘‘Gamma Knife Stereotactic Radiosurgical Boost for
Patients Treated Primarily with Neutron Radiotherapy
for Salivary Gland Neoplasms.’’ Stereotactic and
Functional Neurosurgery 82 (March 2004): 84–89.
Johansen, C. ‘‘Electromagnetic Fields and Health Effects—
Epidemiologic Studies of Cancer, Diseases of the
Central Nervous System and Arrhythmia-Related
Heart Disease.’’ Scandinavian Journal of Work and
Environmental Health 30, Supplement 1 (2004): 1–30.
Lawler, B., A. Pierce, P. J. Sambrook, et al. ‘‘The Diagnosis
and Surgical Management of Major Salivary Gland
Pathology.’’ Australian Dental Journal 49
(March 2004): 9–15.
Wilson, R. T., L. E. Moore, and M. Dosemeci.
‘‘Occupational Exposures and Salivary Gland Cancer
Mortality among African American and White
Workers in the United States.’’ Journal of Occupational
and Environmental Medicine 46 (March 2004): 287–297.
Zheng, R., L. E. Wang, M. L. Bondy, et al. ‘‘Gamma
Radiation Sensitivity and Risk of Malignant and
Benign Salivary Gland Tumors: A Pilot Case-Control
Analysis.’’ Cancer 100 (February 1, 2004): 561–567.
ORGANIZATIONS

SPOHNC, Support for People with Oral and Head and
Neck Cancer. P.O. Box 53, Locust Valley, NY 115600053. 800-377-0928. <http://www.spohnc.org>.
OTHER

‘‘Oral Cavity and Pharyngeal Cancer.’’ American Cancer
Society. Revised May 22, 2000. <http://
www3.cancer.org/cancerinfo>.

Diane M. Calabrese
Rebecca J. Frey, PhD

Salmonella food poisoning
Definition
Salmonella food poisoning is a bacterial food
poisoning caused by the Salmonella bacterium. It
results in the swelling of the lining of the stomach
and intestines (gastroenteritis). While domestic and
wild animals, including poultry, pigs, cattle, and pets
such as turtles, iguanas, chicks, dogs, and cats can
3274

Description
Salmonella food poisoning occurs worldwide,
however it is most frequently reported in North
America and Europe. Only a small proportion of
infected people are tested and diagnosed, and as
few as 1% of cases are actually reported. While the
infection rate may seem relatively low, even an attack
rate of less than 0.5% in such a large number of
exposures results in many infected individuals. The
poisoning typically occurs in small, localized outbreaks in the general population or in large outbreaks
in hospitals, restaurants, or institutions for children
or the elderly. In the United States, Salmonella is
responsible for about 15% of all cases of food
poisoning.
Improperly handled or undercooked poultry and
eggs are the foods which most frequently cause
Salmonella food poisoning. Chickens are a major
carrier of Salmonella bacteria, which accounts for its
prominence in poultry products. However, identifying
foods which may be contaminated with Salmonella
is particularly difficult because infected chickens
typically show no signs or symptoms. Since infected
chickens have no identifying characteristics, these
chickens go on to lay eggs or to be used as meat.
At one time, it was thought that Salmonella bacteria were only found in eggs which had cracked, thus
allowing the bacteria to enter. Ultimately, it was
learned that, because the egg shell has tiny pores,
even uncracked eggs which sat for a time on a surface
(nest) contaminated with Salmonella could themselves
become contaminated. It is known also that the bacteria can be passed from the infected female chicken
directly into the substance of the egg before the shell
has formed around it.
Anyone may contract Salmonella food poisoning,
but the disease is most serious in infants, the elderly,
and individuals with weakened immune systems. In
these individuals, the infection may spread from the
intestines to the blood stream, and then to other body
sites, causing death unless the person is treated
promptly with antibiotics. In addition, people who
have had part or all of their stomach or their spleens
removed, or who have sickle cell anemia, cirrhosis of
the liver, leukemia, lymphoma, malaria, louse-borne
relapsing fever, or Acquired Immunodeficiency
Syndrome (AIDS) are particularly susceptible to
Salmonella food poisoning.
GALE ENCYCLOPEDIA OF MEDICINE

Salmonella food poisoning

Causes and symptoms
Salmonella food poisoning can occur when someone drinks unpasteurized milk or eats undercooked
chicken or eggs, or salad dressings or desserts which
contain raw eggs. Even if Salmonella-containing foods
such as chicken are thoroughly cooked, any food can
become contaminated during preparation if conditions and equipment for food preparation are
unsanitary.
Other foods can then be accidentally contaminated if they come into contact with infected surfaces.
In addition, children have become ill after playing with
turtles or iguanas, and then eating without washing
their hands. Because the bacteria are shed in the feces
for weeks after infection with Salmonella, poor
hygiene can allow such a carrier to spread the infection
to others.
Symptoms appear about one-two days after infection, and include fever (in 50% of patients), nausea and
vomiting, diarrhea, and abdominal cramps and pain.
The diarrhea is usually very liquid, and rarely contains
mucus or blood. Diarrhea usually lasts for about four
days. The illness usually ends in about five-seven days.
Serious complications are rare, occurring most
often in individuals with other medical illnesses.
Complications occur when the Salmonella bacteria
make their way into the bloodstream (bacteremia).
Once in the bloodstream, the bacteria can enter any
organ system throughout the body, causing disease.
Other infections which can be caused by Salmonella
include:


bone infections (osteomyelitis)



joint infections (arthritis)



infection of the sac containing the heart (pericarditis)



infection of the tissues which cover the brain and
spinal cord (meningitis)



infection of the liver (hepatitis)



lung infections (pneumonia)



infection of aneurysms (aneurysms are abnormal
outpouchings which occur in weak areas of the
walls of blood vessels)



infections in the center of already-existing tumors or
cysts.

Diagnosis
Under appropriate laboratory conditions,
Salmonella can be grown and then viewed under a
microscope for identification. Early in the infection,
the blood is far more likely to positively show a
GALE ENCYCLOPEDIA OF MEDICINE

Salmonella enteritidis. Exposure to this bacterium usually
occurs by contact with contaminated food. (Photograph
by Oliver Meckes, Photo Researchers, Inc. Reproduced by
permission.)

presence of the Salmonella bacterium when a sample
is grown on a nutrient substance (culture) for identification purposes. Eventually, however, positive cultures can be obtained from the stool and in some
cases from a urine culture.

Treatment
Even though Salmonella food poisoning is a bacterial infection, most practitioners do not treat simple
cases with antibiotics. Studies have shown that using
antibiotics does not usually reduce the length of time
that the patient is ill. Paradoxically, it appears that
antibiotics do, however, cause the patient to shed
bacteria in their feces for a longer period of time. In
order to decrease the length of time that a particular
individual is a carrier who can spread the disease,
antibiotics are generally not given.
In situations where an individual has a more
severe type of infection with Salmonella bacteria, a
number of antibiotics may be used. Chloramphenicol
was the first antibiotic successfully used to treat
Salmonella food poisoning. It is still a drug of choice
in developing countries because it is so inexpensive,
although some resistance has developed to it.
Ampicillin and trimethoprim-sulfonamide have been
used successfully in the treatment of infections caused
by chloramphenicol-resistant strains. Newer types of
anibiotics, such as cephalosporin or quinolone, are
also effective. These drugs can be given by mouth or
through a needle in the vein (intravenously) for very ill
patients. With effective antibiotic therapy, patients
feel better in 24–48 hours, the temperature returns to
normal in three-five days, and the patient is generally
recovered by 10–14 days.
3275

Salpingectomy

KEY TERMS
Carrier—Someone who has an organism (bacteria,
virus, fungi) in his or her body, without signs of
illness. The individual may therefore pass the
organism on to others.
Gastroenteritis—Inflammation of the stomach and
intestines. Usually causes nausea, vomiting, diarrhea, abdominal pain and cramps.

uncooked eggs (Caesar salad dressing, meringue toppings, mousses) need to be modified to eliminate the
raw eggs. Not only should chicken be cooked thoroughly, until no pink juices flow, but all surfaces and
utensils used on raw chicken must be carefully cleaned
to prevent Salmonella from contaminating other
foods. Careful handwashing is a must before, during,
and after all food preparation involving eggs and
poultry. Handwashing is also important after handling and playing with pets such as turtles, iguanas,
chicks, dogs and cats.
Resources

Alternative treatment
A number of alternative treatments have been
recommended for food poisoning. One very effective
treatment that is stongly recommended is supplementation with Lactobacillus acidophilus, L. bulgaricus,
and/or Bifidobacterium to restore essential bacteria in
the digestive tract. These preparations are available as
powders, tablets, or capsules from health food stores;
yogurt with live L. acidophilus cultures can also be
eaten. Fasting or a liquid-only diet is often used for
food poisoning. Homeopathic treatment can work
very effectively in the treatment of Salmonella food
poisoning. The appropriate remedy for the individual
and his/her symptoms must be used to get the desired
results. Some examples of remedies commonly used
are Chamomilla, Nux vomica, Ipecac, and Colchicum.
Juice therapy, including carrot, beet, and garlic juices,
is sometimes recommended, although it can cause discomfort for some people. Charcoal tablets can help
absorb toxins and remove them from the digestive
tract through bowel elimination. A variety of herbs
with antibiotic action, including citrus seed extract,
goldenseal (Hydrastis canadensis), and Oregon grape
(Mahonia aquifolium), may also be effective in helping
to resolve cases of food poisoning.

Prognosis
The prognosis for uncomplicated cases of
Salmonella food poisoning is excellent. Most people
recover completely within a week’s time. In cases
where other medical problems complicate the illness,
prognosis depends on the severity of the other medical
conditions, as well as the specific organ system
infected with Salmonella.

Prevention
Prevention of Salmonella food poisoning involves
the proper handling and cooking of foods likely to
carry the bacteria. This means that recipes utilizing
3276

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Salmonella paratyphi infection see
Paratyphoid fever
Salmonella typhi infection see Typhoid fever

Salpingectomy
Definition
Salpingectomy is the removal of one or both of a
woman’s fallopian tubes, the tubes through which an
egg travels from the ovary to the uterus.

Purpose
A salpingectomy may be performed for several
different reasons. Removal of one tube (unilateral
salpingectomy) is usually performed if the tube has
become infected (a condition known as salpingitis).
Salpingectomy is also used to treat an ectopic
pregnancy, a condition in which a fertilized egg has
implanted in the tube instead of inside the uterus. In
most cases, the tube is removed only after drug treatments designed to save the structure have failed.
(Women with one remaining fallopian tube are still
able to get pregnant and carry a pregnancy to term.)
The other alternative to salpingectomy is surgery to
remove the fetus from the fallopian tube, followed by
surgery to repair the tube.
A bilateral salpingectomy (removal of both the
tubes) is usually done if the ovaries and uterus are also
going to be removed. If the fallopian tubes and the
GALE ENCYCLOPEDIA OF MEDICINE

Ectopic pregnancy—The development of a fetus at
a site other than the inside of the uterus; most commonly, the egg implants itself in the fallopian tube.
Laparoscope—A surgical instrument with a light
attached that is inserted through the abdominal
wall to allow the surgeon to see the organs in the
abdomen.

ovaries are both removed at the same time, this is called
a salpingo-oophorectomy. A salpingo-oophorectomy
is necessary when treating ovarian and endometrial
cancer because the fallopian tubes and ovaries are the
most common sites to which cancer may spread.

incision. Even when major surgery is performed, most
women are out of bed and walking around within
three days. Within a month or two, a woman can
slowly return to normal activities such as driving,
exercising, and working.

Risks
All surgery, especially under general anesthesia,
carries certain risks, such as the risk of scarring,
hemorrhaging, infection, and reactions to the anesthesia. Pelvic surgery can also cause internal scarring
which can lead to discomfort years afterward.
Resources
ORGANIZATIONS

National Women’s Health Resource Center. 120 Albany St.,
Suite 820, New Brunswick, NJ 08901. (877) 986-9472.
<http://www.healthywomen.org>.

Description
Regional or general anesthesia may be used. Often
a laparoscope (a hollow tube with a light on one end) is
used in this type of operation, which means that the
incision can be much smaller and the recovery time
much shorter.
In this procedure, the surgeon makes a small incision just beneath the navel. The surgeon inserts a short
hollow tube into the abdomen and, if necessary,
pumps in carbon dioxide gas in order to move intestines out of the way and better view the organs. After a
wider double tube is inserted on one side for the
laparoscope, another small incision is made on the
other side through which other instruments can be
inserted. After the operation is completed, the tubes
and instruments are withdrawn. The tiny incisions are
sutured and there is very little scarring.
In the case of a pelvic infection, the surgeon makes
a horizontal (bikini) incision 4-6 in (10-15 cm) long
in the abdomen right above the pubic hairline.
This allows the doctor to remove the scar tissue.
(Alternatively, a surgeon may use a vertical incision
from the pubic bone toward the navel, although this is
less common.)

Carol A. Turkington

Salpingitis see Pelvic inflammatory disease

Salpingo-oophorectomy
Definition
The surgical removal of a fallopian tube and an
ovary.

Purpose
This surgery is performed to treat ovarian or other
gynecological cancers, or infections as a result of pelvic
inflammatory disease. Occasionally, removal of one or
both ovaries may be done to treat endometriosis. If
only one tube and ovary are removed, the woman
may still be able to conceive and carry a pregnancy to
term.

Description
Preparation
The patient is given an injection an hour before
surgery to encourage drowsiness.

Aftercare
Aftercare varies depending on whether the tube
was removed by laparoscopy or through an abdominal
GALE ENCYCLOPEDIA OF MEDICINE

If the procedure is performed through a laparoscope, the surgeon can avoid a large abdominal incision and can shorten recovery. With this technique,
the surgeon makes a small cut through the abdominal
wall just below the navel. When the laparoscope is
used, the patient can be given either regional or general
anesthesia; if there are no complications, the patient
can leave the hospital in a day or two.
3277

Salpingo-oophorectomy

KEY TERMS

Salpingo-oophorectomy

If a laparoscope is not used, the surgery involves
an incision 4–6 in (10–long into the abdomen either
extending vertically up from the pubic bone toward
the navel, or horizontally (the ‘‘bikini incision’’) across
the pubic hairline. The scar from a bikini incision is
less noticeable, but some surgeons prefer the vertical
incision because it provides greater visibility while
operating.

Preparation
A spinal block or general anesthesia may be given
before surgery.

Aftercare
If performed through an abdominal incision,
salpingo-oophorectomy is major surgery that requires
three to six weeks for full recovery. However, if
performed laparascopically, the recovery time can be
much shorter. There may be some discomfort around
the incision for the first few days after surgery, but
most women are walking around by the third day.
Within a month or so, patients can gradually resume
normal activities such as driving, exercising, and
working.
Immediately following the operation, the patient
should avoid sharply flexing the thighs or the knees.
Persistent back pain or bloody or scanty urine indicates that a ureter may have been injured during
surgery.
If both ovaries are removed in a premenopausal
woman as part of the operation, the sudden loss of
estrogen will trigger an abrupt premature menopause
that may involve severe symptoms of hot flashes,
vaginal dryness, painful intercourse, and loss of
sex drive. (This is also called ‘‘surgical menopause.’’)
In addition to these symptoms, women who lose
both ovaries also lose the protection these hormones
provide against heart disease and osteoporosis
many years earlier than if they had experienced
natural menopause. Women who have had their
ovaries removed are seven times more likely to
develop coronary heart disease and much more
likely to develop bone problems at an early age
than are premenopausal women whose ovaries are
intact.
For these reasons, some form of estrogen replacement therapy (ERT) may be prescribed to relieve the
symptoms of surgical menopause and to help prevent
heart and bone disease.
In addition, to help offset the higher risks of heart
and bone disease after loss of the ovaries, women
3278

KEY TERMS
Androgens—Hormones (specifically testosterone)
responsible for male sex characteristics.
Endometriosis—A painful disease in which cells
from the lining of the uterus (endometrium) aren’t
shed during menstruation, but instead attach themselves to other organs in the pelvic cavity. The
condition is hard to diagnose and often causes
severe pain as well as infertility.
Fallopian tubes—Tubes that extend from either end
of the uterus that convey the egg from the ovary to
the uterus during each monthly cycle.
Ureter—The tube that carries urine from the bladder to the kidneys.

should get plenty of exercise, maintain a low-fat diet,
and ensure intake of calcium is adequate.
Reaction to the removal of fallopian tubes and
ovaries depends on a wide variety of factors, including the woman’s age, the condition that required the
surgery, her reproductive history, how much social
support she has, and any previous history of depression. Women who have had many gynecological
surgeries or chronic pelvic pain seem to have a higher
tendency to develop psychological problems after the
surgery.

Risks
Major surgery always involves some risk, including infection, reactions to the anesthesia, hemorrhage,
and scars at the incision site. Almost all pelvic surgery
causes some internal scars, which, in some cases, can
cause discomfort years after surgery.
Resources
ORGANIZATIONS

Midlife Women’s Network. 5129 Logan Ave. S.,
Minneapolis, MN 55419.(800) 886-4354.

Carol A. Turkington

San Joaquin fever see Coccidioidomycosis
Sanfilippo’s syndrome see
Mucopolysaccharidoses
Saquinavir see Protease inhibitors
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Sarcoidosis is a disease which can affect many
organs within the body. It causes the development of
granulomas. Granulomas are masses resembling little
tumors. They are made up of clumps of cells from the
immune system.

Description

Virtually every system of the body has the potential to suffer the effects of sarcoidosis:


tender reddish bumps (nodules) or patches often
appear on the skin



the eyes may become red and teary, and the vision
blurry



the joints may become swollen and painful (arthritis)



lymph nodes in the neck, armpits, and groin become
enlarged and tender, lymph nodes within the chest,
around the lungs, also become enlarged



fluid may accumulate around the lungs (pleural effusion), making breathing increasingly difficult



nasal stuffiness is common, as well as a hoarse sound
to the voice



cysts in the bone may cause pain in the hands and
feet, or in other bony areas



the bone marrow may decrease the production of all
blood cells; decreased number of red blood cells
causes anemia, fewer white blood cells increases the
chance of infections, fewer platelets can increase the
chance of bleeding



the body’s ability to process calcium often becomes
abnormal, so that excess calcium passes through the
kidneys and into the urine; this may cause kidney
stones to form



the liver may become enlarged



the heart may suffer a variety of complications,
including abnormal or missed beats (arrhythmias),
inflammation of the covering of the heart (pericarditis), and an increasing tendency toward weak, ineffective pumping of the blood (heart failure)



Because sarcoidosis has been noted to occur in
family groups, a genetic cause has also been suggested.
Research shows that identical twins are more likely to
both have sarcoidosis than are nonidentical twins or
other siblings.

the nervous system may display the effects of sarcoidosis by hearing loss, chronic inflammation of the
coverings of the brain and spinal cord (meningitis),
abnormalities of the nerve that is involved in vision
(optic nerve dysfunction), seizures, and the development of psychiatric disorders

Some cases of sarcoidosis occur without the
patient even noting any symptoms. These cases are

Any, all, or even none of the above symptoms may
be present in sarcoidosis.

Sarcoidosis is a very puzzling disorder. In addition to having no clear-cut understanding of the cause
of sarcoidosis, researchers are also puzzled by its
distribution in the world population. In the United
States, for example, 10-17 times as many AfricanAmericans are affected as white Americans. In
Europe, whites are primarily affected.
Prevalence is a way of measuring the number of
people affected per 100,000 people in a given population. The prevalence figures for sarcoidosis are very
unusual. In the United States, prevalence figures range
from five (5/100,000 in the United States) for whites to
40 for blacks. In Europe, prevalence ranges from three
in Poland, to 10 in France, to 64 in Sweden, to 200 for
Irish women living in London. Furthermore, a person
from a group with very low prevalence who leaves his
or her native land for a second location with a higher
prevalence will then have the same risk as anyone
living in that second location.
Sarcoidosis affects both men and women,
although women are more likely to have the disorder.
The average age for diagnosis is around 20-40 years.

Causes and symptoms
The cause of sarcoidosis is not known. Because
the granulomas are primarily made up of cells from
the immune system (macrophages and lymphocytes),
an immune connection is strongly suspected. One of
the theories which has been put forth suggests that
exposure to some toxic or infectious material starts
up an immune response. For some reason, the body is
unable to stop the response, and it spreads from the
original organ to other organs.

GALE ENCYCLOPEDIA OF MEDICINE

3279

Sarcoidosis

Sarcoidosis

often discovered by chance during routine chest
x rays. Most cases of sarcoidosis, however, begin
with very nonspecific symptoms, such as decreased
energy, weakness, and a dry cough. Occasionally, the
cough is accompanied by some mild pain in the breastbone (sternum). Some patients note that they are
having unusual shortness of breath while exercising.
Some patients develop fever, decreased appetite, and
weight loss.

Sarcoidosis

Diagnosis

KEY TERMS

Diagnosis depends on information from a number
of sources, including the patient’s symptoms, the physical examination, x-ray pictures of the chest, and a
number of other laboratory examinations of blood or
other tissue. None of these categories of information
are sufficient to make the diagnosis of sarcoidosis.
There is no one test or sign or symptom which clearly
points to sarcoidosis, excluding all other types of diseases. This is because nearly all of the symptoms and
laboratory results in sarcoidosis also occur in other
diseases. Diagnosis, then, requires careful consideration of many facts.

Granuloma—Masses made up of a variety of
immune cells, as well as fibroblasts (cells which
make up connective tissue).
Immune system—The system of specialized
organs, lymph nodes, and blood cells throughout
the body which work together to prevent foreign
invaders (bacteria, viruses, fungi, etc.) from taking
hold and growing.

The physical examination in sarcoidosis may reveal
the characteristic skin lesions. Wheezes may be heard
throughout the lungs. The liver may be enlarged.
Examination of the eyes using a special light called a
slit-lamp may reveal changes indicative of sarcoidosis.

A gallium 67 scan involves the injection of a radioactive material called gallium 67. In sarcoidosis, areas
of the body which are inflamed will retain the gallium
67. These areas will then show up on the scan.

The chest x ray will show some pattern of abnormalities, which may include enlargement of the lymph
nodes which drain the lung, scarring and abnormalities to the tissue of the lungs, and fluid accumulation
around the lungs.
Lung function tests measure such things as the
amount of air an individual can breathe in and breathe
out, the speed at which the air flows in and out, and the
amount of air left in the lung after blowing out as much
as possible in one second. A variety of lung function
tests may show abnormal results in sarcoidosis.
Other types of tests may be abnormal in sarcoidosis. The abnormal test results may also indicate other
diseases. They include an elevation of a substance
called angiotensin-converting enzyme in the blood,
and an increased amount of calcium present in 24
hours worth of urine.
Bronchoscopy is a very helpful diagnostic test. This
involves passing a tiny tube (bronchoscope) through
the nose or mouth, down the trachea, and into the
airways (bronchial tubes). The bronchial tubes can be
inspected through the bronchoscope. The bronchoscope is also designed in such a way as to allow biopsies
to be obtained. Bronchoalveolar lavage involves washing the surfaces with a sterile saltwater (saline) solution.
The saline is then retrieved and examined in a laboratory. Cells and debris from within the bronchial tubes
and the tiny sacs of the lung (the alveoli) will be
obtained in this way, and can be studied for the presence of an abnormally large number of white blood
cells. A tiny piece of the lung tissue can also be obtained
through the bronchosocope. This can be studied under
a microscope to look for the characteristic granulomas
and inflammation of sarcoidosis.
3280

Treatment
Many cases of sarcoidosis resolve without treatment. If treatment is needed, the most effective one for
sarcoidosis is the administration of steroid medications. These medications work to decrease inflammation throughout the body. The long-term use of
steroid medications has serious potential side-effects.
Patients are only treated with steroids when the problems caused by sarcoidosis are particularly serious.
Many cases of sarcoidosis resolve without treatment.

Prognosis
The prognosis for sarcoidosis is quite good.
About 60-70% of the time, sarcoidosis cures itself
within a year or two. In about 20-30% of patients,
permanent damage occurs to the lungs. About 15-20%
of all patients go on to develop a chronic, relapsing
form of sarcoidosis. Death can be blamed on sarcoidosis in about 10% of all sarcoidosis cases.

Prevention
Until researchers are able to pinpoint the cause of
sarcoidosis, there will be no available recommendations for how to prevent it.
Resources
PERIODICALS

Zitkus, Bruce S. ‘‘Sarcoidosis: Varied Symptoms Often
Impede Diagnosis of this Multisystem Disorder.’’
American Journal of Nursing 97, no. 10 (October
1997): 40+.

Rosalyn Carson-DeWitt, MD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
A sarcoma is a bone tumor that contains cancer
(malignant) cells. A benign bone tumor is an abnormal
growth of noncancerous cells.

Description
A primary bone tumor originates in or near a
bone. Most primary bone tumors are benign, and the
cells that compose them do not spread (metastasize) to
nearby tissue or to other parts of the body.
Malignant primary bone tumors account for
fewer than 1% of all cancers diagnosed in the United
States. They can infiltrate nearby tissues, enter the
bloodstream, and metastasize to bones, tissues, and
organs far from the original malignancy. Malignant
primary bone tumors are characterized as either:


bone cancers which originate in the hard material of
the bone.



soft-tissue sarcomas which begin in blood vessels,
nerves, or tissues containing muscles, fat, or fiber.
Types of bone tumors

Osteogenic sarcoma, or osteosarcoma, is the most
common form of bone cancer, accounts for 6% of all
instances of the disease, and for about 5% of all cancers that occur in children. Nine hundred new cases of
osteosarcoma are diagnosed in the United States every
year. The disease usually affects teenagers, and is
almost twice as common in boys as in girls.
Osteosarcomas, which grow very rapidly, can
develop in any bone but most often occur along the
edge or on the end of one of the fast-growing long
bones that support the arms and legs. About 80% of
all osteosarcomas develop in the parts of the upper
and lower leg nearest the knee (the distal femur or in
the proximal tibia). The next likely location for an
osteosarcoma is the bone of the upper arm closest to
the shoulder (the proximal humerus).

Chondrosarcomas are cancerous bone tumors
that most often appear in middle age. Usually originating in strong connective tissue (cartilage) in ribs or
leg or hip bones, chondrosarcomas grow slowly. They
rarely spread to the lungs. It takes years for a chondrosarcoma to metastasize to other parts of the body,
and some of these tumors never spread.
Parosteal osteogenic sarcomas, fibrosarcomas,
and chordomas are rare. Parosteal osteosarcomas generally involve both the bone and the membrane that
covers it. Fibrosarcomas originate in the ends of the
bones in the arm or leg, and then spread to soft tissue.
Chordomas develop on the skull or spinal cord.
Osteochondromas, which usually develop between
age 10-20, are the most common noncancerous primary
bone tumors. Giant cell tumors generally develop in a
section of the thigh bone near the knee. Giant cell
tumors are originally benign but sometimes become
malignant.

Causes and symptoms
The cause of bone cancer is unknown, but the
tendency to develop it may be inherited. Children
who have bone tumors are often tall for their age,
and the disease seems to be associated with growth
spurts that occur during childhood and adolescence.
Injuries can make the presence of tumors more apparent but do not cause them.
A bone that has been broken or exposed to high
doses of radiation used to treat other cancers is more
likely than other bones to develop osteosarcoma. A
history of noncancerous bone disease also increases
bone-cancer risk.
The amount of radiation in diagnostic x rays
poses little or no danger of bone-cancer development,
but children who have a family history of the most
common childhood cancer of the eye (retinoblastoma),
or who have inherited rare cancer syndromes have a
greater-than-average risk of developing bone cancer.
Exposure to chemicals found in some paints and dyes
can slightly raise the risk.

Ewing’s sarcoma is the second most common
form of childhood bone cancer. Accounting for fewer
than 5% of bone tumors in children, Ewing’s sarcoma
usually begins in the soft tissue (the marrow) inside
bones of the leg, hips, ribs, and arms. It rapidly infiltrates the lungs, and may metastasize to bones in other
parts of the body.

Both benign and malignant bone tumors can distort and weaken bone and cause pain, but benign
tumors are generally painless and asymptomatic.

More than 80% of patients who have Ewing’s
sarcoma are white, and the disease most frequently

It is sometimes possible to feel a lump or mass, but
pain in the affected area is the most common early

GALE ENCYCLOPEDIA OF MEDICINE

3281

Sarcomas

Sarcomas

affects children between ages 5-9, and young adults
between ages 20-30. About 27% of all cases of Ewing’s
sarcoma occur in children under age 10, and 64%
occur in adolescents between ages 10-20.

Sarcomas

symptom of bone cancer. Pain is not constant in the
initial stages of the disease, but it is aggravated by
activity and may be worse at night. If the tumor is
located on a leg bone, the patient may limp. Swelling
and weakness of the limb may not be noticed until
weeks after the pain began.

cells have infiltrated other tissues, and help surgeons
decide which portion of a growth would be best to
biopsy. Because more than four of every five malignant bone tumors metastasize to the lungs, a CAT
scan of the chest is performed to see if these organs
have been affected. Chest and abdominal CAT scans
are used to determine whether Ewing’s sarcoma has
spread to the lungs, liver, or lymph nodes.

Other symptoms of bone cancer include:


a bone that breaks for no apparent reason



difficulty moving the affected part of the body



fatigue



fever



a lump on the trunk, an arm or leg, or another bone



persistent, unexplained back pain



weight loss

Diagnosis



Magnetic resonance imaging (MRI) is a specialized
scan that relies on radio waves and powerful magnets
to reflect energy patterns created by tissue abnormalities and specific diseases. An MRI provides more
detailed information than does a CAT scan about
tumors and marrow cavities of the bone, and can
sometimes detect clusters of cancerous cells that
have separated from the original tumor. This valuable information helps surgeons select the most
appropriate approach for treatment.



Radionuclide bone scans. These scans involve injecting a small amount of radioactive material into a
vein. Primary tumors or cells that have metastasized
absorb the radioactive material and show up as dark
spots on the scan.

Physical examination and routine x rays may yield
enough evidence to diagnose benign bone tumors, but
removal of tumor tissue for microscopic analysis
(biopsy) is the only sure way to rule out malignancy.
A needle biopsy involves using a fine, thin needle
to remove small bits of tumor, or a thick needle to
extract tissue samples from the innermost part (the
core) of the growth. An excisional biopsy is the surgical removal of a small, accessible tumor. An incisional
biopsy is performed on tumors too large or inaccessible to be completely removed. The surgeon performing an incisional biopsy cuts into the patient’s skin and
removes a portion of the exposed tumor. Performed
under local or general anesthetic, biopsy reveals
whether a tumor is benign or malignant and identifies
the type of cancer cells the malignant tumor contains.
Bone cancer is usually diagnosed about three
months after symptoms first appear, and 20% of
malignant tumors have metastasized to the lungs or
other parts of the body by that time.
Imaging techniques
The following procedures are used, in conjunction
with biopsy, to diagnose bone cancer:


Bone x rays. These x rays usually provide a clear
image of osteosarcomas.



Computerized axial tomography (CAT scan) is a
specialized x ray that uses a rotating beam to obtain
detailed information about an abnormality and its
physical relationship to other parts of the body. A
CAT scan can differentiate between osteosarcomas
and other types of bone tumors, illustrate how tumor

3282

Cytogenic and molecular genetic studies, which
assess the structure and composition of chromosomes
and genes, may also be used to diagnose osteosarcoma. These tests can sometimes indicate what form
of treatment is most appropriate.
Laboratory studies
A complete blood count (CBC) reveals abnormalities in the blood, and may indicate whether bone
marrow has been affected. A blood test that measures
levels of the enzyme lactate dehydrogenase (LDH)
can predict the likelihood of a specific patient’s
survival.
Immunohistochemistry involves adding special
antibodies and chemicals, or stains, to tumor samples.
This technique is effective in identifying cells that are
found in Ewing’s sarcoma but are not present in other
malignant tumors.
Reverse
transcription
polymerase
chain
reaction (RTPCR) relies on chemical analysis of the
substance in the body that transmits genetic information (RNA) to:


evaluate the effectiveness of cancer therapies



identify mutations consistent with the presence of
Ewing’s sarcoma



reveal cancer that recurs after treatment has been
completed
GALE ENCYCLOPEDIA OF MEDICINE

A specimen of a femur bone indicating the cancerous growth
around the knee. Osteosarcoma is the most common primary
cancer of the bone. (Photo Researchers, Inc. Reproduced by
permission.)



Chemotherapy. Chemotherapy is usually administered in addition to surgery, to kill cancer cells that
have separated from the original tumor and spread
to other parts of the body. Although chemotherapy
can increase the likelihood of later development of
another form of cancer, the American Cancer
Society maintains that the need for chemotherapeutic bone-cancer treatment is much greater than the
potential risk.



Surgery. Surgery, coordinated with diagnostic
biopsy, enhances the probability that limb-salvage
surgery can be used to remove the cancer while preserving nearby blood vessels and bones. A metal rod
or bone graft is used to replace the area of bone
removed, and subsequent surgery may be needed to
repair or replace rods that have loosened or broken.
Patients who have undergone limb-salvage surgery
need intensive rehabilitation. It may take as long as a
year for a patient to regain full use of a leg following
limb-salvage surgery, and patients who have this
operation may eventually have to undergo
amputation.



Radiation therapy. Radiation therapy is used often to
treat Ewing’s sarcoma.



Rotationoplasty. Rotationoplasty, sometimes performed after a leg amputation, involves attaching
the lower leg and foot to the thigh bone, so that the
ankle replaces the knee. A prosthetic is later added to
make the leg as long as it should be. Prosthetic
devices are not used to lengthen limbs that remain
functional after amputation to remove osteosarcomas located on the upper arm. When an osteosarcoma develops in the jaw bone, the entire lower jaw is
removed. Bones from other parts of the body are
later grafted on remaining bone to create a new jaw.

Staging
Once bone cancer has been diagnosed, the tumor
is staged. This process indicates how far the tumor has
spread from its original location. The stage of a tumor
suggests which form of treatment is most appropriate,
and predicts how the condition will probably respond
to therapy.
An osteosarcoma may be localized or metastatic.
A localized osteosarcoma has not spread beyond the
bone where it arose or beyond nearby muscles, tendons, and other tissues. A metastatic osteosarcoma
has spread to the lungs, to bones not directly connected to the bone in which the tumor originated, or
to other tissues or organs.

Treatment
Since the 1960s, when amputation was the only
treatment for bone cancer, new chemotherapy drugs
and innovative surgical techniques have improved survival with intact limbs. Because osteosarcoma is so
rare, patients should consider undergoing treatment
at a major cancer center staffed by specialists familiar
with the disease.
A treatment plan for bone cancer, developed after
the tumor has been diagnosed and staged, may
include:


Amputation. Amputation may be the only therapeutic option for large tumors involving nerves or blood
vessels that have not responded to chemotherapy.
MRI scans indicate how much of the diseased limb
must be removed, and surgery is planned to create
a cuff, formed of muscles and skin, around the
amputated bone. Following surgery, an artificial

GALE ENCYCLOPEDIA OF MEDICINE

Follow-up treatments
After a patient completes the final course of chemotherapy, CAT scans, bone scans, x rays, and other
diagnostic tests may be repeated to determine if any
traces of tumor remain. If none are found, treatment is
discontinued, but patients are advised to see their
oncologist and orthopedic surgeon every two or
three months for the next year. X rays of the chest
and affected bone are taken every four months. An
annual echocardiogram is recommended to evaluate
any adverse effect chemotherapy may have had on the
heart, and CT scans are performed every six months.
3283

Sarcomas

(prosthetic) leg is fitted over the cuff. A patient who
actively participates in the rehabilitation process may
be walking independently as soon as three months
after the amputation.

Sarcomas

Patients who have received treatment for Ewing’s
sarcoma are examined often - at gradually lengthening
intervals - after completing therapy. Accurate growth
measurements are taken during each visit and blood is
drawn to be tested for side effects of treatment. X rays,
CT scans, bone scans, and other imaging studies are
generally performed every three months during the
first year. If no evidence of tumor growth or recurrence is indicated, these tests are performed less frequently in the following years.
Some benign bone tumors shrink or disappear
without treatment. However, regular examinations
are recommended to determine whether these tumors
have changed in any way.

Alternative treatment
Alternative treatments should never be substituted for conventional bone-cancer treatments or
used without the approval of a physician. However,
some alternative treatments can be used as adjunctive
and supportive therapies during and following conventional treatments.
Dietary adjustments can be very helpful for
patients with cancer. Whole foods, including grains,
beans, fresh fruits and vegetables, and high quality
fats, should be emphasized in the diet, while processed
foods should be avoided. Increased consumption of
fish, especially cold water fish like salmon, mackerel,
halibut, and tuna, provides a good source of omega-3
fatty acids. Nutritional supplements can build strength
and help maintain it during and following chemotherapy, radiation, or surgery. These supplements should
be individually prescribed by an alternative practitioner
who has experience working with cancer patients.
Many cancer patients claim that acupuncture alleviates pain, nausea, and vomiting. It can also be effective
in helping to maintain energy and relative wellness
during surgery, chemotherapy, and radiation. Massage,
reflexology, and relaxation techniques are said to
relieve pain, tension, anxiety, and depression. Exercise
can be an effective means of reducing mental and emotional stress, while increasing physical strength. Guided
imagery, biofeedback, hypnosis, body work, and progressive relaxation can also enhance quality of life.
Claims of effectiveness in fighting cancer have
been made for a variety of herbal medicines. These
botanical remedies work on an individual basis and
should only be used when prescribed by a practitioner
familiar with cancer treatment.
Treating cancer is a complex and individual task.
It should be undertaken by a team of support
3284

practitioners with varying specialities who can work
together for healing the person with cancer.

Prognosis
Benign brain tumors rarely recur, but sarcomas
can reappear after treatment was believed to have
eliminated every cell.
Likelihood of long-term survival depends on:


the type and location of the tumor



how much the tumor has metastasized, and on what
organs, bones, or tissues have been affected

More than 85% of patients survive for more than
five years after complete surgical removal of low-grade
osteosarcomas (tumors that arise in mature tissue and
contain a small number of cancerous cells). About 2530% of patients diagnosed with high-grade osteosarcomas (tumors that develop in immature tissue and
contain a large number of cancer cells) will die of the
disease.
Two-thirds of all children diagnosed with Ewing’s
sarcoma will live for more than five years after the
disease is detected. The outlook is most favorable for
children under age 10, and least favorable in patients
whose cancer is not diagnosed until after it has metastasized: fewer than three of every 10 of these patients
remain alive five years later. More than 80% of
patients whose Ewing’s sarcoma is confined to a
small area and surgically removed live, for at least
five years. Postsurgical radiation and chemotherapy
add years to their lives. More than 70% of patients live
five years or more with a small Ewing’s sarcoma that
cannot be removed, but only three out of five patients
with large, unremovable tumors survive that long.

Prevention
There is no known way to prevent bone cancer.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345.
<http://www.cancer.org>.
CancerCare, Inc. 1180 Avenue of the Americas, New York,
NY 10036. (800) 813-4673.
<http://www.cancercare.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Maureen Haggerty
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Saw palmetto is an extract derived from the deep
purple berries of the saw palmetto fan palm (Serenoa
repens), a plant indigenous to the coastal regions of the
southern United States and southern California.
There is an estimated one million acres of wild saw
palmetto palms in Florida, where the bulk of commercial saw palmetto is grown.

Purpose
Saw palmetto is used by natural health practitioners
to treat a variety of ailments in men and women, such
as testicular inflammation, urinary tract inflammation,
coughs, and respiratory congestion. It is also used to
strengthen the thyroid gland, balance the metabolism,
stimulate appetite, and aid digestion. According to the
American Dietetic Association, saw palmetto is one of
the most commonly used dietary supplements among
Americans between the ages of 50 and 76.
Most of the evidence supporting these uses is
anecdotal and has not been proven by controlled
clinical trials. However, there is much scientific documentation outlining the effectiveness of the herb in
treating irritable bladder and urinary problems in men
with benign prostate hyperplasia (BPH), an enlargement of the prostate gland. BPH results in a swelling of
the prostate gland that obstructs the urethra. This
causes painful urination, reduced urine flow, difficulty
starting or stopping the flow, dribbling after urination, and more frequent nighttime urination. Saw
palmetto does not reduce prostate enlargement.
Instead, it is thought to work in a variety of ways.
First, it inhibits the conversion of testosterone into
dihydrotestosterone (DHT). BPH is thought to be
caused by an increase in testosterone to DHT.
Secondly, saw palmetto is believed to interfere with
the production of estrogen and progesterone, hormones associated with DHT production.
In addition to causing pain and embarrassment,
BPH can lead to serious kidney problems if undiagnosed and left untreated. It is a common problem in
men over the age of 40. Estimates are that 50–60% of
all men will develop BPH in their lifetimes. It is estimated that there are six million men between the ages
of 50–79 who have BPH serious enough to require
some type of therapy. Yet only half of them seek
treatment from physicians. Health practitioners in
both the allopathic and natural medicine communities
recommend annual prostate examinations for men
GALE ENCYCLOPEDIA OF MEDICINE

Recently, a number of clinical trials have confirmed the effectiveness of saw palmetto in treating
BPH. Many of these trials have shown saw palmetto
works better than the most commonly used prescription drug, Proscar. Saw palmetto is effective in nearly
90% of patients after six weeks of use, while Proscar is
effective in less than 50% of patients. In addition,
Proscar may take up to six months to achieve its full
effect. Since Proscar blocks the production of testosterone, it can cause impotence and breast enlargement.
Also, saw palmetto is significantly less expensive than
Proscar. A one-month supply of saw palmetto costs
$12–25, while a one month supply of Proscar costs
$65–75. Other prescription drugs used to treat BPH
are Cardura (doxazosin), Hytrin (terazosin), and
Flomax (tamsulosin hydrochloride). Originally prescribed to treat hypertension, Cardura and Hytrin
can drop blood pressure, causing lightheadedness
and fainting. Presently, saw palmetto is being evaluated by the U.S. Food and Drug Administration
(FDA) for treatment of BPH. If approved, it would
become the first herbal product to be licensed by the
agency as a treatment for a specific condition. Saw
palmetto is also used as a treatment for prostate complaints and irritable bladder.
Since the 1960s, extensive clinical studies of saw
palmetto have been done in Europe. A 1998 review of
24 European trials involved nearly 3,000 men, some
taking saw palmetto, others taking Proscar, and a
third group taking a placebo. The men taking saw
palmetto had a 28% improvement in urinary tract
symptoms, a 24% improvement in peak urine flow,
and 43% improvement in overall urine flow. The
results were nearly comparable to the group taking
Proscar and superior to the men taking a placebo.
On the other hand, saw palmetto does not appear
to be useful in treating prostatitis or chronic pelvic
pain syndrome (CPPS) in men. A group of researchers
at Columbia University reported in early 2004 that
men given saw palmetto for CP/CPPS showed no
appreciable improvement at the end of a year-long
trial.
Uses in women
There is very little documentation or scientific
research into saw palmetto use in women. However,
several studies in the 1990s show that the BPH drug
Proscar can be effective in stopping unwanted facial
and body hair growth, and in treating thinning hair in
3285

Saw palmetto

Saw palmetto

over the age of 50, and an annual blood test that
measures prostate specific antigen, a marker for prostate cancer.

Saw palmetto
Saw palmetto leaves. (Photo Researchers, Inc. Reproduced by permission.)

women. It works by blocking the action of an enzyme
called 5-alpha reductase. Anecdotal reports suggest
that saw palmetto may be as effective as Proscar in
treating unwanted hair growth and thinning hair, and
in preventing some types of acne. It has also been used
to treat urinary tract inflammation and help relieve the
symptoms of menstruation. There are claims it can be
used to enlarge breasts, but these claims have not been
scientifically tested.
History
Saw palmetto berries have been used in American
folk medicine for several hundred years as an aphrodisiac and for treating prostate problems. Native
Americans in the southeast United States have used
saw palmetto since the 1700s to treat male urinary
problems. In the 1800s, medical botanist John Lloyd
noted that animals that ate saw palmetto appeared
healthier and fatter than other livestock. Early
American settlers noticed the same effects and used
the juice from saw palmetto berries to gain weight, to
improve general disposition, as a sedative, and to
promote reproductive health.
3286

In the United States, the medicinal uses of saw
palmetto were first documented in 1879 by Dr. J. B.
Read, a physician in Savannah, Georgia, who published a paper on the medicinal benefits of the herb in
the April 1879 issue of American Journal of Pharmacy.
He found the herb useful in treating a wide range of
conditions. ‘‘By its peculiar soothing power on the
mucous membrane it induces sleep, relieves the most
troublesome coughs, promotes expectoration,
improves digestion, and increases fat, flesh and
strength. Its sedative and diuretic properties are
remarkable,’’ Read wrote. ‘‘Considering the great
and diversified power of the saw palmetto as a therapeutic agent, it seems strange that it should have so
long escaped the notice of the medical profession.’’
A pungent tea made from saw palmetto berries
was commonly used in the early 1900s to treat prostate
enlargement and urinary tract infections. It was also
used in men to increase sperm production and sex
drive, although these uses are discounted today. One
of the first published medical recommendations that
saw palmetto was effective in treating prostate problems appeared in the 1926 edition of United States
Dispensatory. In the late 1920s, the use of medicinal
GALE ENCYCLOPEDIA OF MEDICINE

Preparations
The National Institute on Aging recommends
that people taking saw palmetto should obtain it
only from reputable sources. In addition, people
should use only standardized extracts that contain
85–95% fatty acids and sterols. Dosages vary
depending on the type of saw palmetto used. A typical dose is 320 mg per day of standardized extract
(1–2 g) per day of ground dried whole berries. It may
take up to four weeks of use before beneficial effects
are seen. In late 1999, the web-based independent
consumer organization ConsumerLab.com tested 27
leading brands of saw palmetto for fatty acid and
sterol content. Ten of the brands contained less than
the minimum recommended level of 85% fatty acids
and sterols.

Precautions
There are no special precautions associated with
taking saw palmetto, even in high doses. However,
BPH can become a serious problem if left untreated.
Men who are experiencing symptoms should be
examined by a physician, since the symptoms of
BPH are similar to those of prostate cancer. Men
over the age of 50 should have a yearly prostate
exam. Saw palmetto should only be used under a
doctor’s supervision by people with prostate cancer,
breast cancer, or any sex hormone related diseases.
Although the effects of saw palmetto on a fetus is
unknown, pregnant women are advised not to take
saw palmetto. Saw palmetto can alter hormonal
activity that could have an adverse effect on the
fetus. Women taking birth control pills or estrogen
replacement products should consult a physician
before taking saw palmetto. Persons taking testosterone or other anabolic steroids should not take saw
palmetto without first consulting their doctor.
In rare cases, allergic reactions to saw palmetto
have been reported. Symptoms include difficulty
breathing, constricting of the throat, hives, and swelling of the lips, tongue, or face. Persons experiencing
any of these symptoms should stop taking saw palmetto and seek immediate medical attention.

Side effects
The only reported minor side effects are rare and
include cramps, nausea, diarrhea, and headache.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anabolic steroids—A group of mostly synthetic
hormones sometimes taken by athletes to temporarily increase muscle size.
Aphrodisiac—Any substance that excites sexual
desire.
Estrogen—A hormone that stimulates development
of female secondary sex characteristics.
Placebo—An inert or innocuous substance used in
controlled experiments testing the efficacy of
another substance.
Progesterone—A steroid hormone that is a biological precursor to corticoid (another steroid hormone) and androgen (a male sex hormone).
Testosterone—A male hormone produced in the
testes or made synthetically that is responsible for
male secondary sex characteristics.
Urethra—The canal that carries urine from the
bladder.

Interactions
Saw palmetto may interfere with such hormonerelated drugs as testosterone and estrogen replacements, including Premarin, Cenestin, Vivelle,
Fempatch, and Climara. It may also interact with
such birth control pills as Triphasil, Ovral, Lo-Ovral,
Nordette, Alesse, Demulen, and Ortho-Novum.
Anyone on these types of medications should consult
their doctor before taking saw palmetto. There are no
known restrictions on food, beverages, or physical
activity while taking saw palmetto.
Several herbs and minerals have been used in
conjunction with saw palmetto in treating BPH. A
1996 European study showed positive results in
treating patients with a daily dose of 320 mg of
saw palmetto extract and 240 mg of nettle root
extract. Many alternative health practitioners also
recommend saw palmetto be used in combination
with the herb pygeum africanum, pumpkin seeds,
zinc, flaxseed oil, certain amino acids, antioxidants,
and diets high in protein and soy products. Some
factors that can impair the effectiveness of saw
palmetto include beer, cigarette smoke, and some
chemical pesticides used on fruit and vegetables.
Some physicians recommend using saw palmetto
in addition to a prescription medicine, such as
Proscar, Hytrin, or Cardura.
3287

Saw palmetto

plants, including saw palmetto, began to decline in the
United States, while at the same time, it was on the rise
in Europe.

Scabies

Resources
BOOKS

Foster, Steven W. Guide to Herbal Dosages. Loveland, CO:
Interweave Press, 2000.
PERIODICALS

D’Epiro, Nancy Walsh. ‘‘Saw Palmetto and the Prostate.’’
Patient Care April 15, 1999: 29.
Gong, E. M., and G. S. Gerber. ‘‘Saw Palmetto and Benign
Prostatic Hyperplasia.’’ American Journal of Chinese
Medicine 32 (March 2004): 331–338.
Gunther, S., R. E. Patterson, A. R. Kristal, et al.
‘‘Demographic and Health-Related Correlates of
Herbal and Specialty Supplement Use.’’ Journal of the
American Dietetic Association 104 (January 2004):
27–34.
Kaplan, S. A., M. A. Volpe, and A. E. Te. ‘‘A Prospective, 1Year Trial Using Saw Palmetto Versus Finasteride in
the Treatment of Category III Prostatitis/Chronic
Pelvic Pain Syndrome.’’ Journal of Urology 171
(January 2004): 284–288.
Peng, C. C., P. A. Glassman, L. E. Trilli, et al. ‘‘Incidence
and Severity of Potential Drug-Dietary Supplement
Interactions in Primary Care Patients: An Exploratory
Study of 2 Outpatient Practices.’’ Archives of Internal
Medicine 164 (March 22, 2004): 630–636.
ORGANIZATIONS

National Institute on Aging (NIA) Information Center. P.
O. Box 8057, Gaithersburg, MD 20892-8057. (800) 2222225. <http://www.nih.gov/nia>.

Ken R. Wells
Rebecca J. Frey, PhD

Scabies
Definition
Scabies is a relatively contagious infection caused
by a tiny mite(Sarcoptes scabiei).

Description
Scabies is caused by a tiny insect about 0.3 mm
long called a mite. When a human comes in contact
with the female mite, the mite burrows under the skin,
laying eggs along the line of its burrow. These eggs
hatch, and the resulting offspring rise to the surface of
the skin, mate, and repeat the cycle either within the
skin of the original host, or within the skin of its next
victim.
3288

An enhanced image of a scab mite. (Custom Medical Stock
Photo. Reproduced by permission.)

The intense itching almost always caused by scabies is due to a reaction within the skin to the feces of
the mite. The first time someone is infected with scabies, he or she may not notice any itching for a number
of weeks (four to six weeks). With subsequent infections, the itchiness will begin within hours of picking
up the first mite.

Causes and symptoms
Scabies is most common among people who live in
overcrowded conditions, and whose ability to practice
good hygiene is limited. Scabies can be passed between
people by close skin contact. Although the mites can
only live away from human skin for about three days,
sharing clothing or bedclothes can pass scabies among
family members or close contacts. In May 2002, the
Centers for Disease Control (CDC) included scabies in
its updated guidelines for the treatment of sexually
transmitted diseases.
The itching, or pruritus, from scabies is worse
after a hot shower and at night. Burrows are seen as
winding, slightly raised gray lines along the skin. The
female mite may be seen at one end of the burrow, as a
tiny pearl-like bump underneath the skin. Because of
the intense itching, burrows may be obscured by
scratch marks left by the patient. The most common
locations for burrows include the sides of the fingers,
between the fingers, the top of the wrists, around the
elbows and armpits, around the nipples of the breasts
in women, in the genitalia of men, around the waist
(beltline), and on the lower part of the buttocks.
Babies may have burrows on the soles of their feet,
palms of their hands, and faces.
Scratching seems to serve some purpose in scabies,
as the mites are apparently often inadvertently
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Several types of lotions (usually containing 5%
permethrin) can be applied to the body, and left on
for 12–24 hours. One topical application is usually
sufficient, although the scabicide may be reapplied
after a week if mites remain. Preparations containing lindane are no longer recommended for treating
scabies as of 2003 because of the potential for
damage to the nervous system. Itching can be lessened by the use of calamine lotion or antihistamine medications.

Scab mites have penetrated under the skin of this person’
hand. (Custom Medical Stock Photo. Reproduced by permission.)

removed. Most infestations with scabies are caused by
no more than 15 mites altogether.
Infestation with huge numbers of mites (on the
order of thousands to millions) occurs when an individual does not scratch, or when an individual has a
weakened immune system. These patients include
those who live in institutions; are mentally retarded,
or physically infirm; have other diseases which affect
the amount of sensation they have in their skin
(leprosy or syringomyelia); have leukemia or diabetes;
are taking medications which lower their immune
response (cancerchemotherapy, drugs given after
organ transplantation); or have other diseases which
lower their immune response (such as acquired immunodeficiency syndrome or AIDS). This form of scabies,
with its major infestation, is referred to as crusted
scabies or Norwegian scabies. Infected patients have
thickened, crusty areas all over their bodies, including
over the scalp. Their skin is scaly. Their fingernails
may be thickened and horny.

Diagnosis
Diagnosis can be made simply by observing the
characteristic burrows of the mites causing scabies. A
sterilized needle can be used to explore the pearly
bump at the end of a burrow, remove its contents,
and place it on a slide to be examined. The mite itself
may then be identified under a microscope.
GALE ENCYCLOPEDIA OF MEDICINE

In addition to topical medications, the doctor
may prescribe oral ivermectin. Ivermectin is a drug
that was originally developed for veterinary practice
as a broad-spectrum antiparasite agent. Studies
done in humans, however, have found that ivermectin is as safe and effective as topical medications for
treating scabies. A study published in 2003 reported
that ivermectin is safe for people in high-risk categories, including those with compromised immune
systems.

Prognosis
The prognosis for complete recovery from scabies
infestation is excellent. In patients with weak immune
systems, the biggest danger is that the areas of skin
involved with scabies will become secondarily infected
with bacteria.

Prevention
Good hygiene is essential in the prevention of
scabies. When a member of a household is diagnosed with scabies, all that person’s recently-worn
clothing and bedding should be washed in very hot
water.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Scabies (The Itch).’’ Section 10, Chapter 114 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Burroughs, R. F., and D. M. Elston. ‘‘What’s Eating You?
Canine Scabies.’’ Cutis 72 (August 2003): 107–109.
3289

Scabies

Occasionally, a type of mite carried on dogs
(Sarcoptes scabiei var. canis) may infect humans.
These mites cannot survive for very long on humans,
and so the infection is very light.

Scabies
Scabies is a contagious skin infection common among people who live in overcrowded, less than ideal hygienic environments.
It is caused by the infestation of female scab mites that, upon contact, burrows under the victim’s skin and lays eggs along the
lines of passage. Once the eggs hatch, the new mites rise to the skin’s surface, mate, and repeats the infestation. Scabies can
occur anywhere on the body, including the armpit, groin, buttocks, genital area, and ankles, as shown in the illustration above.
(Illustration by Electronic Illustrators Group.)

KEY TERMS
Mite—An insect parasite belonging to the order
Acarina. The organism that causes scabies is a mite.
Pruritus—An unpleasant itching sensation. Scabies
is characterized by intense pruritus.
Topical—A type of medication applied to the skin
or body surface.

Fawcett, R. S. ‘‘Ivermectin Use in Scabies.’’ American
Family Physician 68 (September 15, 2003): 1089–1092.
Santoro, A. F., M. A. Rezac, and J. B. Lee. ‘‘Current Trend
in Ivermectin Usage for Scabies.’’ Journal of Drugs in
Dermatology 2 (August 2003): 397–401.
ORGANIZATIONS

American Academy of Dermatology (AAD). 930 East
Woodfield Road, Schaumburg, IL 60173. (847) 3300230. <http://www.aad.org>.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD
Burstein, G. R., and K. A. Workowski. ‘‘Sexually
Transmitted Diseases Treatment Guidelines.’’ Current
Opinion in Pediatrics 15 (August 2003): 391–397.
3290

Scarlatina see Scarlet fever
GALE ENCYCLOPEDIA OF MEDICINE

G L A D Y S D I C K (1881–1963)

Definition
Scarlet fever is an infection that is caused by a
bacteria called streptococcus. The disease is characterized by a sore throat, fever, and a sandpaper-like rash
on reddened skin. It is primarily a childhood disease. If
scarlet fever is untreated, serious complications such
as rheumatic fever (a heart disease) or kidney inflammation (glomerulonephritis) can develop.

Description
Scarlet fever, also known as scarlatina, gets its
name from the fact that the patient’s skin, especially on the cheeks, is flushed. A sore throat and
raised rash over much of the body are accompanied
by fever and sluggishness (lethargy). The fever
usually subsides within a few days and recovery is
complete by two weeks. After the fever is gone, the
skin on the face and body flakes; the skin on the
palms of the hands and soles of the feet peels more
dramatically.
This disease primarily affects children ages two to
ten. It is highly contagious and is spread by sneezing,
coughing, or direct contact. The incubation period is
three to five days, with symptoms usually beginning
on the second day of the disease, and lasting from four
to ten days.
Early in the twentieth century, severe scarlet fever
epidemics were common. Today, the disease is rare.
Although this decline is due in part to the availability
of antibiotics, that is not the entire reason since the
decline began before the widespread use of antibiotics.
One theory is that the strain of bacteria that causes
scarlet fever has become weaker with time.

Causes and symptoms
Scarlet fever is caused by Group A streptococcal
bacteria (S. pyogenes). Group A streptococci can be
highly toxic microbes that can cause strep throat,
wound or skin infections, pneumonia, and serious kidney infections, as well as scarlet fever. The Group A
streptococci are; hemolytic bacteria, which means that
the bacteria have the ability to lyse or break red blood
cells. The strain of streptococcus that causes scarlet
fever is slightly different from the strain that causes
most strep throats. The scarlet fever strain of bacteria
produces a toxin, called an erythrogenic toxin. This
toxin is what causes the skin to flush.
GALE ENCYCLOPEDIA OF MEDICINE

Before 1922, not much was known about the thenendemic disease of scarlet fever, which primarily
affected children in Europe and North America, killing
about 25% of the children who contracted it.
Additionally, scarlet fever had many complications,
some of which were severe and could be crippling.
Gladys Dick, with her husband, George Dick, successfully isolated the bacteria which caused scarlet fever,
developed a test for human vulnerability to the disease,
and devised preventive methods. The couple patented
their findings, specifically the way their scarlet fever
toxin and antitoxin were prepared, although this decision was controversial at the time.
In 1923, the Dicks published papers in which they
proved that scarlet fever was caused by hemolytic streptococcus. Within a few years, the Dicks also published
papers on how to prevent, test, diagnose, and treat scarlet
fever. Their groundbreaking work ensured that the disease was finally understood and brought under control.
Dick and her husband announced the development
of what came to be known as the Dick test in 1924. This
skin test showed whether the patient was susceptible or
immune to scarlet fever. The test involved injecting a
toxin-containing substance in the arm and determining
if the skin around the area became inflamed. If it did, the
patient was vulnerable to scarlet fever. This test was also
useful in predicting if pregnant women would develop
puerperal infection during childbirth.

The main symptoms and signs of scarlet fever are
fever, lethargy, sore throat, and a bumpy rash that
blanches under pressure. The rash appears first on
the upper chest and spreads to the neck, abdomen,
legs, arms, and in folds of skin such as under the arm
or groin. In scarlet fever, the skin around the mouth
tends to be pale, while the cheeks are flushed. The
patient usually has a ‘‘strawberry tongue,’’ in which
inflamed bumps on the tongue rise above a bright red
coating. Finally, dark red lines (called Pastia’s lines)
may appear in the creases of skin folds.

Diagnosis
Cases of scarlet fever are usually diagnosed and
treated by pediatricians or family medicine practitioners. The chief diagnostic signs of scarlet fever are
the characteristic rash, which spares the palms and
soles of the feet, and the presence of a strawberry
tongue in children. Strawberry tongue is rarely seen
in adults.
3291

Scarlet fever

Scarlet fever

Scarlet fever

The doctor will take note of the signs and symptoms to eliminate the possibility of other diseases.
Scarlet fever can be distinguished from measles, a
viral infection that is also associated with a fever and
rash, by the quality of the rash, the presence of a sore
throat in scarlet fever, and the absence of the severe
eye inflammation and severe runny nose that usually
accompany measles.
The doctor will also distinguish between a strep
throat, a viral infection of the throat, and scarlet fever.
With a strep infection, the throat is sore and appears
beefy and red. White spots appear on the tonsils.
Lymph nodes under the jawline may swell and become
tender. However, none of these symptoms are specific
for strep throat and may also occur with a viral infection. Other signs are more characteristic of bacterial
infections. For example, inflammation of the lymph
nodes in the neck is typical in strep infections, but not
viral infections. On the other hand, cough, laryngitis,
and stuffy nose tend to be associated with viral infections rather than strep infections. The main feature
that distinguishes scarlet fever from a mere strep
throat is the presence of the sandpaper-red rash.
Laboratory tests are needed to make a definitive
diagnosis of a strep infection and to distinguish a strep
throat from a viral sore throat. One test that can be
performed is a blood cell count. Bacterial infections
are associated with an elevated white blood cell count.
In viral infections, the white blood cell count is generally below normal.
A throat culture can distinguish between a strep
infection and a viral infection. A throat swab from the
infected person is brushed over a nutrient gel (a sheep
blood agar plate) and incubated overnight to detect
the presence of hemolytic bacteria. In a positive culture, a clear zone will appear in the gel surrounding the
bacterium, indicating that a strep infection is present.

Treatment
Although scarlet fever will often clear up spontaneously within a few days, antibiotic treatment with
either oral or injectable penicillin is usually recommended to reduce the severity of symptoms, prevent
complications, and prevent spread to others.
Antibiotic treatment will shorten the course of the
illness in small children but may not do so in adolescents or adults. Nevertheless, treatment with antibiotics is important to prevent complications.
Since penicillin injections are painful, oral penicillin may be preferable. If the patient is unable to tolerate penicillin, alternative antibiotics such as
3292

KEY TERMS
Clindamycin—An antibiotic that can be used
instead of penicillin.
Erythrogenic toxin—A toxin or agent produced by
the scarlet fever-causing bacteria that causes the
skin to turn red.
Erythromycin—An antibiotic that can be used
instead of penicillin.
Glomerulonephritis—A serious inflammation of the
kidneys that can be caused by streptococcal bacteria;
a potential complication of untreated scarlet fever.
Hemolytic bacteria—Bacteria that are able to burst
red blood cells.
Lethargy—The state of being sluggish.
Pastia’s lines—Red lines in the folds of the skin,
especially in the armpit and groin, that are characteristic of scarlet fever.
Penicillin—An antibiotic that is used to treat bacterial infections.
Procaine penicillin—An injectable form of penicillin that contains an anesthetic to reduce the pain of
the injection.
Rheumatic fever—A heart disease that is a complication of a strep infection.
Sheep blood agar plate—A petri dish filled with a
nutrient gel containing red blood cells that is used
to detect the presence of streptococcal bacteria in a
throat culture. Streptococcal bacteria will lyse or
break the red blood cells, leaving a clear spot
around the bacterial colony.
Strawberry tongue—A sign of scarlet fever in
which the tongue appears to have a red coating
with large raised bumps.

erythromycin or clindamycin may be used. However,
the entire course of antibiotics, usually 10 days, will
need to be followed for the therapy to be effective.
Because symptoms subside quickly, there is a temptation to stop therapy prematurely. It is important to
take all of the pills in order to kill the bacteria. Not
completing the course of therapy increases the risk of
developing rheumatic fever and kidney inflammation.
If the patient is considered too unreliable to take
all of the pills or is unable to take oral medication,
daily injections of procaine penicillin can be given in
the hip or thigh muscle. Procaine is an anesthetic that
makes the injections less painful.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
If treated promptly with antibiotics, full recovery
is expected. Once a patient has had scarlet fever, they
develop immunity and cannot develop it again.

Keloid and hypertophic scars have similar
appearances. However, the keloid scar expands
beyond the original wound.
The location of the wound also has an effect on its
size. If the scar is located on places like the knee or
shoulder, it will eventually widen because these areas
are in motion.
Treatment could minimize a scar but will not erase
the mark.

Prevention
Avoiding exposure to children who have the disease will help prevent the spread of scarlet fever.
Resources
BOOKS

Bennett, J. Claude, and Fred Plum, editors. Cecil Textbook
of Medicine. Philadelphia: W. B. Saunders Co., 1996.

Sally J. Jacobs, EdD

Causes and symptoms
Scarring is the natural process of repairing an
open wound, injury, surgical incision, or other conditions like acne. Initially, a scar is red because blood
vessels are created while the body forms scar tissue.
The damaged area is covered by a protective scab that
eventually falls off. The scar may become brown or
pink. It generally fades over time and becomes less
visible.
The healing process takes from one year to 18
months. Some scars heal naturally. Other scars require
additional treatment.

Scars
Definition
Scars are marks created during the healing of
damage to the skin or tissues.

Description
A scar is a manifestation of the skin’s healing
process. After skin or tissue is wounded, the body
releases collagen to mend the damage. Collagen, a
protein, reattaches the damaged skin. As the wound
heals, a temporary crust forms and covers it. The crust
is a scab that protects the damaged area.
Causes of scars include cuts, sores, surgery, and
burns. Severe acne and chicken pox may also scar skin.
The degree that skin scars depends on more than the
size and depth of the wound. Age also affects the
process. The healing process is stronger in younger
skin. That results in scars that are thicker than those
of older people. Other factors affecting the type of scar
are ethnicity, heredity, and the location of the injury.
Children are active and susceptible to cuts and
injuries. They and people with fair complexions tend
to get hypertophic scars. While Asians and blacks are
likely to have keloid scars, people from other ethnic
groups also experience this form of scarring.
GALE ENCYCLOPEDIA OF MEDICINE

Hypertophic scars and keloids
Hypertophic scars and keloids are caused by an
over-active healing process. This produces an excessive amount of collagen at the wound site. Both types
of scars are red, thick, and raised above the wound.
Hypertophic scars do not extend beyond the
wound site. The scar may itch and usually heals without professional treatment in about a year.
Keloids are large scars that could form after surgery, an injury, burn, or body piercing. This scarring
often occurs on the ear lobe or chest. Sometimes
keloids develop spontaneously.
The keloid is raised, rigid, and grows beyond the
wound. The keloid can continue to grow. Scars are
generally harmless, but may itch or feel tender. In
addition, a person may feel self-conscious about the
scar’s appearance.
Contracture scars
Contracture scars are caused by the loss of a
large section of skin due to burns or other injury.
The scar contracts or tightens around the wound.
This contraction could impact a person’s mobility.
If the scar deepens, it could affect muscles and
nerves.
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Scars

Bed rest is not necessary, nor is isolation of the
patient. Aspirin or Tylenol (acetaminophen) may be
given for fever or relief of pain.

Scars

Acne scars
Acne scars may appear after the severe stage of
acne, a skin condition usually caused by hormonal
changes. The inflammatory condition is seen in adolescence, but acne can occur later in life.
Severe acne is triggered by clogged pores that
cause bacteria to multiply. It occurs more frequently
in adolescent boys than girls. If the acne is not treated,
there could be scarring. The types of scars include pitlike pockmarks.

Diagnosis
Since visible scars could make people self-conscious, they will probably seek treatment rather than
a diagnosis. Medical professionals who treat scars
include dermatologists and plastic surgeons.
Dermatologists are physicians who care for the skin.
Their expertise includes three or more years of medical
and surgical training.
Scar treatment is usually not covered by insurance. Cosmetic procedures, those done to improve a
person’s appearance, are considered elective surgery
and are paid for by the patient. However, if scars cause
a physical impairment, coverage may be issued.
Examples of impairments include burn scars and
keloids that restrict motion. For coverage to be
approved, it is helpful for the primary care doctor to
document the patient’s case in writing.

Treatment
A scar is permanent and cannot be completely
removed. However, treatment can alter a scar’s
appearance. These procedures range from the application of over-the-counter ointment to surgery. Scar
treatment should start after an injury because wound
care affects scarring. The wound should be cleaned
and covered. Picking at the scab breaks the collagen
and allows germs to enter the wound. Time also helps
with healing. Scars become smaller, and the color
fades.
However, additional treatment is required for
some scars. While some procedures are more effective
for keloids and hypertrophic scars, the procedure for
acne scars is based on the type of scarring. Treatment
for burn scars may include skin grafts surgery.
Surgery
The surgical procedure for scars is referred to as
scar revision because the procedure modifies the scar’s
appearance. The cost of scar revision averaged $1,129
3294

in 2003, according to a membership survey of the
American Academy of Facial Plastic and
Reconstructive Surgery (AAFPRS).
This procedure works well on scars that are wide
or long. Other treatments may be recommended for
keloids because a surgical incision could cause a new
scar and create another keloid. To reduce the risk of
another scar, surgery may be followed by the injection
of cortisone steroids.
Steroid Injections
Steroid injection is a singular form of treatment
for scars, particularly keloid and hypertophic scars.
Corticosteroids are an anti-inflammatory drug that
helps to lessen the scar’s red color and thickness. The
treatment flattens the scar and helps with itching.
Injection costs vary and could cost $150 per scar,
according to a member of the American Academy of
Dermatologists (AAD).
Cyrosurgery
Cryosurgery involves the freezing of freezes tissue
with a probe containing nitrous oxide. It is used to
modify scars, especially keloid and hypertrophic scars.
Treatment vary could cost $175 per lesion, according
to the AAD member.
Dermabrasion
Dermabrasion is the removal of a layer of the
skin’s surface. Scars including those caused by acne
are smoothed or sanded by an instrument. The procedure costs approximately $150 per treatment.
Silicone gel sheets
Silicone gel sheets can be purchased over-thecounter. The sheets are worn over the scar area to
seal moisture. The treatment helps with itching and
to reduce scar thickness and color. Cost of sheets for
small wounds ranges from $30 to $50.

Alternative treatment
Alternate methods of treating scars range from
applying Vitamin E to massaging the skin. People
should consult with a doctor or other health care
professional before starting treatment involving contact with the scarred area.
These procedures include applying obtained
Vitamin E, aloe vera, or cocoa butter to the scar.
Vitamin E is sold as an oil or obtained by opening a
vitamin capsule. Aloe is an African plant and is sold I
GALE ENCYCLOPEDIA OF MEDICINE

Those items are thought to help with healing so
that a scar is less visible. However, time also helps to
lessen the scar’s appearance. Those substances should
be applied only after a scar is well-healed.
Massaging mild scars is done to relax rigid scar
tissue. The scar is massaged for about two minutes.
Afterwards, Vitamin E oil is applied to the skin. The
process should be discontinued if the area becomes
sore or red.

Prognosis
The prognosis for scar treatment depends on factors including the type and severity of the scar. Keloids
may return, and all scars are permanent. If treatment
does not completely minimize a scar to the patient’s
satisfaction, the person can apply make-up to the
scarred area.

OTHER

Treatment of Scars WebMD Medical Reference in collaboration with the Cleveland Clinic, Department of
Plastic Surgery. September 2003 [cited March 28, 2005].
<http://my.webmd.com/content/article/76/
90236.htm>.
What is a Scar?Academy of Dermatology pamphlet, 2004
[cited March 28, 2005]. <http://www.aad.org/public/
Publications/pamphlets/WhatisaScar.htm>.
AAFPRS 2003 Statistics on Trends in Facial Plastic Surgery
American Academy of Facial Plastic and
Reconstructive Surgery. 2004 [cited March 28, 2005}.
<http://www.aafprs.org/media/stats_polls/
AAFPRS%20MEDIA%202004%20-%20Final.pd>.

Liz Swain

Schatzki’s ring see Lower esophageal ring

Prevention
The primary way to prevent scarring is to avoid
injuries. People should wear protective gear when participating in sports. Furthermore, acne should be treated before the condition reaches the severe stage.
If injured, a person should immediately treat the
wound because this reduces the risk of scarring. The
wound should be cleaned and covered. If stitches
aren’t needed, a butterfly bandage is effective at keeping the wound closed. Moreover, a balanced diet also
helps with the healing process.
Picking at the scab should be avoided because this
interferes with the healing process and raises the risk
of scarring.
Resources
BOOKS

Turkington, Carol. Skin Deep: An A-Z of Skin Disorders,
Treatments, and Health. Facts on File, Inc., 1998.
PERIODICALS
ORGANIZATIONS

American Academy of Dermatology. 1350 I Street NW,
Suite 870, Washington, DC 20005-4355. 202-842-3555.
<http://www.aad.org>.
American Academy of Facial Plastic and Reconstructive
Surgery. 310 South Henry Street, Alexandria, VA
22314. 703) 299-9291. <http://www.aafprs.org>.
American Society of Plastic Surgeons, Plastic Surgery
Educational Foundation. 444 East Algonquin Road,
Arlington Heights, IL 60005. 847-228-9900. <http://
www.plasticsurgery.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Schistosomiasis
Definition
Schistosomiasis, also known as bilharziasis or
snail fever, is a primarily tropical parasitic disease
caused by the larvae of one or more of five types of
flatworms or blood flukes known as schistosomes. The
name bilharziasis comes from Theodor Bilharz, a
German pathologist, who identified the worms in 1851.

Description
Infections associated with worms present some of
the most universal health problems in the world. In
fact, only malaria accounts for more diseases than
schistosomiasis. The World Health Organization
(WHO) estimates that 200 million people are infected
and 120 million display symptoms. Another 600 million people are at risk of infection. Schistosomes are
prevalent in rural and outlying city areas of 74 countries in Africa, Asia, and Latin America. In Central
China and Egypt, the disease poses a major health risk.
There are five species of schistosomes that are
prevalent in different areas of the world and produce
somewhat different symptoms:


Schistosoma mansoni is widespread in Africa, the
Eastern-Mediterranean, the Caribbean, and South
America and can only infect humans and rodents.



S. mekongi is prevalent only in the Mekong river
basin in Asia.
3295

Schistosomiasis

capsule form and as a skin care product. Cocoa butter
is a fat made from cacao seeds.

Schistosomiasis



S. japonicum is limited to China and the Philippines
and can infect other mammals, in addition to humans,
such as pigs, dogs, and water buffalos. As a result, it
can be harder to control disease caused by this species.



S. intercalatum is found in central Africa.



S. haematobium occurs predominantly in Africa and
the Eastern Mediterranean.

Intestinal schistosomiasis, caused by Schistosoma
japonicum, S. mekongi, S. mansoni, and S. intercalatum, can lead to serious complications of the liver
and spleen. Urinary schistosomiasis is caused by
S. haematobium.
It is difficult to know how many individuals die of
schistomiasis each year because death certificates and
patient records seldom identify schistosomiasis as the
primary cause of death. Mortality estimates vary
related to the type of schistosome infection but is
generally low, for example, 2.4 of 100,000 die each
year from infection with S. mansoni.

Causes and symptoms
All five species are contracted in the same way,
through direct contact with fresh water infested with
the free-living form of the parasite known as cercariae.
The building of dams, irrigation systems, and reservoirs, and the movements of refugee groups introduce
and spread schistosomiasis.
Eggs are excreted in human urine and feces and, in
areas with poor sanitation, contaminate freshwater
sources. The eggs break open to release a form of the
parasite called miracidium. Freshwater snails become
infested with the miracidium, which multiply inside the
snail and mature into multiple cercariae that the snail
ejects into the water. The cercariae, which survive outside a host for 48 hours, quickly penetrate unbroken
skin, the lining of the mouth, or the gastrointestinal
tract. Once inside the human body, the worms penetrate the wall of the nearest vein and travel to the liver
where they grow and sexually mature. Mature male and
female worms pair and migrate either to the intestines
or the bladder where egg production occurs. One
female worm may lay an average of 200 to 2,000 eggs
per day for up to twenty years. Most eggs leave the
blood stream and body through the intestines. Some of
the eggs are not excreted, however, and can lodge in the
tissues. It is the presence of these eggs, rather than the
worms themselves, that causes the disease.
Early symptoms of infection
Many individuals do not experience symptoms. If
present, it usually takes four to six weeks for symptoms
3296

to appear. The first symptom of the disease may be a
general ill feeling. Within twelve hours of infection, an
individual may complain of a tingling sensation or light
rash, commonly referred to as ‘‘swimmer’s itch,’’ due to
irritation at the point of entrance. The rash that may
develop can mimic scabies and other types of rashes.
Other symptoms can occur two to ten weeks later and
can include fever, aching, cough, diarrhea, or gland
enlargement. These symptoms can also be related to
avian schistosomiasis, which does not cause any further
symptoms in humans.
Katayama fever
Another primary condition, called Katayama
fever, may also develop from infection with these
worms, and it can be very difficult to recognize.
Symptoms include fever, lethargy, the eruption of
pale temporary bumps associated with severe itching
(urticarial) rash, liver and spleen enlargement, and
bronchospasm.
Intestinal schistosomiasis
In intestinal schistosomiasis, eggs become lodged
in the intestinal wall and cause an immune system
reaction called a granulomatous reaction. This
immune response can lead to obstruction of the
colon and blood loss. The infected individual may
have what appears to be a potbelly. Eggs can also
become lodged in the liver, leading to high blood
pressure through the liver, enlarged spleen, the buildup of fluid in the abdomen (ascites), and potentially
life-threatening dilations or swollen areas in the esophagus or gastrointestinal tract that can tear and bleed
profusely (esophageal varices). Rarely, the central nervous system may be affected. Individuals with chronic
active schistosomiasis may not complain of typical
symptoms.
Urinary tract schistosomiasis
Urinary tract schistosomiasis is characterized by
blood in the urine, pain or difficulty urinating, and
frequent urination and are associated with S. haematobium. The loss of blood can lead to iron deficiency
anemia. A large percentage of persons, especially children, who are moderately to heavily infected experience urinary tract damage that can lead to blocking of
the urinary tract and bladder cancer.

Diagnosis
Proper diagnosis and treatment may require a
tropical disease specialist because the disease can be
GALE ENCYCLOPEDIA OF MEDICINE

Ascites—The condition that occurs when the liver
and kidneys are not functioning properly and a
clear, straw-colored fluid is excreted by the membrane that lines the abdominal cavity (peritoneum).
Cercariae—The free-living form of the schistosome
worm that has a tail, swims, and has suckers on its
head for penetration into a host.
Miracidium—The form of the schistosome worm
that infects freshwater snails.

schistosome that induces an immune response.
Persons infected with schistosomiasis may not test
positive for six months, and as a result, tests may
need to be repeated to obtain an accurate diagnosis.
Blood can be detected visually in the urine or with
chemical strips that react to small amounts of blood.
Sophisticated imaging techniques, such as ultrasound, computed tomography scan (CT scan), and
magnetic resonance imaging (MRI), can detect damage
to the blood vessels in the liver and visualize polyps
and ulcers of the urinary tract, for example, that occur
in the more advanced stages. S. haematobium is difficult to diagnose with ultrasound in pregnant women.
A scanning electron microscopy (SEM) of the head region of
the male and female adult flukes of Schistosoma sp. These
worms cause schistosomiasis (bilharziasis) in humans.
Flukes live in human blood vessels and their eggs contaminate freshwater. (Photo Researchers, Inc. Reproduced by
permission.)

confused with malaria or typhoid in the early stages.
The healthcare provider should do a thorough history
of travel in endemic areas. The rash, if present, can
mimic scabies or other rashes, and the gastrointestinal
symptoms may be confused with those caused by bacterial illnesses or other intestinal parasites. These other
conditions will need to be excluded before an accurate
diagnosis can be made. As a result, clinical evidence of
exposure to infected water along with physical findings, a negative test for malaria, and an increased
number of one type of immune cell, called an eosinophil, are necessary to diagnose acute schistosomiasis.
Eggs may be detected in the feces or urine.
Repeated stool tests may be required to concentrate
and identify the eggs. Blood tests may be used to detect
a particular antigen or particle associated with the
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
The use of medications against schistosomiasis,
such as praziquantel (Biltricide), oxamniquine, and
metrifonate, have been shown to be safe and effective.
Praziquantel is effective against all forms of schistososmiasis and has few side effects. This drug is given in
either two or three doses over the course of a single
day. Oxamniquine is typically used in Africa and
South America to treat intestinal schistosomiasis.
Metrifonate has been found to be safe and effective
in the treatment of urinary schistosomiasis. Patients
are typically checked for the presence of living eggs at
three and six months after treatment. If the number of
eggs excreted has not significantly decreased, the
patient may require another course of medication.

Prognosis
If treated early, prognosis is very good and complete recovery is expected. The illness is treatable, but
people can die from the effects of untreated schistomiasis. The severity of the disease depends on the
number of worms, or worm load, in addition to how
3297

Schistosomiasis

KEY TERMS

Schizoaffective disorder

long the person has been infected. With treatment, the
number of worms can be substantially reduced, and
the secondary conditions can be treated. The goal of
the World Health Organization is to reduce the severity of the disease rather than to completely stop transmission of the disease. There is, however, little natural
immunity to reinfection. Treated individuals do not
usually require retreatment for two to five years in
areas of low transmission. The World Health
Organization has made research to develop a vaccine
against the disease one of its priorities.

Prevention
Prevention of the disease involves several targets
and requires long term community commitment.
Infected patients require diagnosis, treatment, and
education about how to avoid reinfecting themselves
and others. Adequate healthcare facilities need to be
available, water systems must be treated to kill the
worms and control snail populations, and sanitation
must be improved to prevent the spread of the
disease.
To avoid schistosomiasis in endemic areas:


contact the CDC for current health information on
travel destinations.



upon arrival, ask an informed local authority about
the infestation of schistosomiasis before being
exposed to freshwater in countries that are likely to
have the disease.



do not swim, stand, wade, or take baths in untreated
water.



treat all water used for drinking or bathing. Water
can be treated by letting it stand for three days,
heating it for five minutes to around 1228F (around
508C), or filtering or treating water chemically, with
chlorine or iodine, as with drinking water.



Should accidental exposure occur, infection can be
prevented by hastily drying off or applying rubbing
alcohol to the exposed area.

Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Ruth E. Mawyer, RN

Schizencephaly see Congenital brain defects
3298

Schizoaffective disorder
Definition
Schizoaffective disorder is a mental illness that
shares the psychotic symptoms of schizophrenia and
the mood disturbances of depression or bipolar
disorder.

Description
The term schizoaffective disorder was first used in
the 1930s to describe patients with acute psychotic
symptoms such as hallucinations and delusions along
with disturbed mood. These patients tended to function well before becoming psychotic; their psychotic
symptoms lasted relatively briefly; and they tended to
do well afterward. Over the years, however, the term
schizoaffective disorder has been applied to a variety
of patient groups. The current definition contained in
the American Psychiatric Association’s Diagnostic and
Statistical Manual of Mental Disorders IV (DSM-IV)
recognizes patients with schizoaffective disorder as
those whose mood symptoms are sufficiently severe
to warrant a diagnosis of depression or other fullblown mood disorder and whose mood symptoms
overlap at some period with psychotic symptoms
that satisfy the diagnosis of schizophrenia (e.g. hallucinations, delusions, or thought process disorder).

Causes and symptoms
The cause of schizoaffective disorder remains
unknown and subject to continuing speculation.
Some investigators believe schizoaffective disorder is
associated with schizophrenia and may be caused by a
similar biological predisposition. Others disagree,
stressing the disorder’s similarities to mood disorders
such as depression and bipolar disorder (manic
depression). They believe its more favorable course
and less intense psychotic episodes are evidence that
schizoaffective disorder and mood disorders share a
similar cause.
Many researchers, however, believe schizoaffective
disorder may owe its existence to both disorders. These
researchers believe that some people have a biologic
predisposition to symptoms of schizophrenia that varies along a continuum of severity. On one end of the
continuum are people who are predisposed to psychotic symptoms but never display them. On the other end
of the continuum are people who are destined to
develop outright schizophrenia. In the middle are
those who may at some time show symptoms of
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms of schizoaffective disorder vary considerably from patient to patient. Delusions, hallucinations, and evidence of disturbances in thinking–as
observed in full-blown schizophrenia–may be seen.
Similarly, mood fluctuations such as those observed in
major depression or bipolar disorder may also be seen.
These symptoms tend to appear in distinct episodes that
impair the individual’s ability to function well in daily
life. But between episodes, some patients with schizoaffective disorder remain chronically impaired while
some may do quite well in day-to-day living.

Diagnosis
There are no accepted tissue or brain imaging tests
or techniques to diagnose schizophrenia, mood disorders, or schizoaffective disorder. Instead, physicians
look for the hallmark signs and symptoms of schizoaffective disorder described above, and they attempt to
rule out other illnesses or conditions that may produce
similar symptoms. These include:


Mania. True manic patients can experience episodes
of hallucinations and delusions similar to those seen
in schizoaffective disorder; but these do not persist
for long periods after the mania recedes, as they do in
schizoaffective disorder.



Psychotic depression. Patients with psychotic depression experience hallucinations and delusions similar
to those seen in schizoaffective disorder; but these
symptoms do not persist after the depressive symptoms recede, as they do in schizoaffective disorder.



Schizophrenia. Depressed mood, mania, or other
symptoms may be present in patients with schizophrenia, but patients with schizoaffective disorder will meet
all the criteria set out for a full-blown mood disorder.



Medical and neurological disorders that mimic psychotic/affective disorders.

GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Antipsychotic medications used to treat schizophrenia and the antidepressant drugs and mood stabilizers used in depression and bipolar disorder are the
primary treatments for schizoaffective disorder.
Unfortunately these treatments have not been
well studied in controlled investigations. Studies suggest that traditional antipsychotics such as haloperidol
are effective in treating psychotic symptoms. Newer
generation antipsychotics, such as clozaril and risperidone, have not been as well studied, but also appear
effective. For patients with symptoms of bipolar disorder, lithium is often the mood stabilizer of choice;
and it is often augmented with an anticonvulsant such
as valproate. For those with depressive symptoms, the
evidence supporting the use of antidepressant medications in addition to antipsychotic medications is more
mixed. Electroconvulsive therapy (electric shock) is frequently tried in patients who otherwise do not respond
to antidepressant or mood stabilizing drugs.
While the mainstay of treatment for schizoaffective disorder is antipsychotic medications and mood
stabilizers, certain forms of psychotherapy for both
patients and family members can be useful. Therapy
designed to provide structure and help augment
patients’ ability to solve problems may aid in improving patients’ ability to function in the day-to-day
world, reducing stress and the risk of recurrence.
Vocational and other rehabilitative training can help
patients to work on skills they need to develop.
Whereas hospitalization may be necessary for acute
psychotic episodes, half-way houses and day hospitals
can provide needed treatment while serving as a bridge
for patients to reenter the community.

Alternative treatment
While alternative therapies should never be considered a replacement for medication, these treatments can
help support people with schizoaffectve disorder and
other mental illnesses. Dietary modifications that eliminate processed foods and emphasize whole foods, along
with nutritional supplementation, may be helpful.
Acupuncture, homeopathy, and botanical medicine can
support many aspects of the person’s life and may help
decrease the side effects of any medications prescribed.

Prognosis
In general, patients with schizoaffective disorder
have a more favorable prognosis than do those with
schizophrenia, but a less favorable course than those
with a pure mood disorder. Medication and other
3299

Schizoaffective disorder

schizophrenia, but require some other major trauma to
set the progression of the disease into motion. It may be
an early brain injury–either through a complicated
delivery, prenatal exposure to the flu virus or illicit
drugs; or it may be emotional, nutritional or other
deprivation in early childhood. In this view, major life
stresses, or a mood disorder like depression or bipolar
disorder, may be sufficient to trigger the psychotic
symptoms. In fact, patients with schizoaffective disorder frequently experience depressed mood or mania
within days of the appearance of psychotic symptoms.
Some clinicians believe that ‘‘schizomanic’’ patients are
fundamentally different from ‘‘schizodepressed’’ types;
the former are similar to bipolar patients, while the
latter are a very heterogeneous group.

Schizophrenia

KEY TERMS
Bipolar disorder—Also referred to as manic
depression, it is a mood disorder marked by alternating episodes of extremely low mood (depression) and exuberant highs (mania).
Mood disorder—A collection of disorders that
includes major depression and bipolar disorder.
They are all characterized by major disruptions in
patients’ moods and emotions.
Schizophrenia—A major mental illness marked by
psychotic symptoms, including hallucinations,
delusions, and severe disruptions in thinking.

interventions can help quell psychotic symptoms and
stabilize mood in many patients, but there is great
variability in outcome from patient to patient.

Prevention
There is no known way to prevent schizoaffective
disorder. Treatment with antipsychotic and mood stabilizing drugs may prevent recurrences. Some
researchers believe prompt treatment can prevent the
development of full-blown schizophrenia, but this
remains the subject of some disagreement.

features of their environment. Most schizophrenics,
if untreated, gradually withdraw from interactions
with other people, and lose their ability to take care
of personal needs and grooming.
The prevalence of schizophrenia is thought to be
about 1% of the population around the world; it is
thus more common than diabetes, Alzheimer’s disease,
or multiple sclerosis. In the United States and Canada,
patients with schizophrenia fill about 25% of all hospital beds. The disorder is considered to be one of the
top ten causes of long-term disability worldwide.

Description

Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
National Alliance for Research on Schizophrenia and
Depression. 60 Cutter Mill Road, Suite 200, Great
Neck, NY 11021. (516) 829-0091. <http://
www.mhsource.com>.

Richard H. Camer

Schizophrenia
Definition
Schizophrenia is a psychotic disorder (or a group
of disorders) marked by severely impaired thinking,
emotions, and behaviors. Schizophrenic patients are
typically unable to filter sensory stimuli and may have
enhanced perceptions of sounds, colors, and other
3300

(Photo Researchers Inc. Reproduced by permission.)

The course of schizophrenia in adults can be
divided into three phases or stages. In the acute
phase, the patient has an overt loss of contact with
reality (psychotic episode) that requires intervention
and treatment. In the second or stabilization phase,
the initial psychotic symptoms have been brought
under control but the patient is at risk for relapse if
treatment is interrupted. In the third or maintenance
phase, the patient is relatively stable and can be kept
indefinitely on antipsychotic medications. Even in the
maintenance phase, however, relapses are not unusual
and patients do not always return to full functioning.
The English term schizophrenia comes from two
Greek words that mean ‘‘split mind.’’ It was observed
around 1908, by a Swiss doctor named Eugen Bleuler,
to describe the splitting apart of mental functions that
he regarded as the central characteristic of
schizophrenia.
Recently, some psychotherapists have begun to
use a classification of schizophrenia based on two
main types. People with Type I, or positive schizophrenia, have a rapid (acute) onset of symptoms and
GALE ENCYCLOPEDIA OF MEDICINE

There are five subtypes of schizophrenia:
Paranoid
The key feature of this subtype of schizophrenia is
the combination of false beliefs (delusions) and hearing voices (auditory hallucinations), with more nearly
normal emotions and cognitive functioning (cognitive
functions include reasoning, judgment, and memory).
The delusions of paranoid schizophrenics usually
involve thoughts of being persecuted or harmed by
others or exaggerated opinions of their own importance, but may also reflect feelings of jealousy or
excessive religiosity. The delusions are typically organized into a coherent framework. Paranoid schizophrenics function at a higher level than other
subtypes, but are at risk for suicidal or violent behavior under the influence of their delusions.
Disorganized
Disorganized schizophrenia (formerly called
hebephrenic schizophrenia) is marked by disorganized
speech, thinking, and behavior on the patient’s part,
coupled with flat or inappropriate emotional
responses to a situation (affect). The patient may act
silly or withdraw socially to an extreme extent. Most
patients in this category have weak personality structures prior to their initial acute psychotic episode.

do not meet the specific criteria for the paranoid,
disorganized, or catatonic subtypes.
Residual
This category is used for patients who have had at
least one acute schizophrenic episode but do not presently have strong positive psychotic symptoms, such
as delusions and hallucinations. They may have negative symptoms, such as withdrawal from others, or
mild forms of positive symptoms, which indicate that
the disorder has not completely resolved.
The risk of schizophrenia among first-degree biological relatives is ten times greater than that observed
in the general population. Furthermore the presence
of the same disorder is higher in monozygotic twins
(identical twins) than in dizygotic twins (nonidentical
twins). The research concerning adoption studies and
identical twins also supports the notion that environmental factors are important, because not all relatives
who have the disorder express it. There are several
chromosomes and loci (specific areas on chromosomes which contain mutated genes), which have
been identified. Research is actively ongoing to elucidate the causes, types and variations of these
mutations.
Most patients are diagnosed in their late teens or
early twenties, but the symptoms of schizophrenia can
emerge at any age in the life cycle. The male/female
ratio in adults is about 1.2:1. Male patients typically
have their first acute episode in their early twenties,
while female patients are usually closer to age 30 when
they are recognized with active symptoms.
Schizophrenia is rarely diagnosed in preadolescent children, although patients as young as five or
six have been reported. Childhood schizophrenia is at
the upper end of the spectrum of severity and shows a
greater gender disparity. It affects one or two children
in every 10,000; the male/female ratio is 2:1.

Catatonic
Catatonic schizophrenia is characterized by disturbances of movement that may include rigidity, stupor, agitation, bizarre posturing, and repetitive
imitations of the movements or speech of other people.
These patients are at risk for malnutrition, exhaustion,
or self-injury. This subtype is presently uncommon in
Europe and the United States. Catatonia as a symptom is most commonly associated with mood disorders.
Undifferentiated
Patients in this category have the characteristic
positive and negative symptoms of schizophrenia but
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Theories of causality
One of the reasons for the ongoing difficulty in
classifying schizophrenic disorders is incomplete
understanding of their causes. It is thought that these
disorders are the end result of a combination of
genetic, neurobiological, and environmental causes.
A leading neurobiological hypothesis looks at the connection between the disease and excessive levels of
dopamine, a chemical that transmits signals in the
brain (neurotransmitter). The genetic factor in schizophrenia has been underscored by recent findings that
3301

Schizophrenia

tend to respond well to drugs. They also tend to suffer
more from the ‘‘positive’’ symptoms, such as delusions
and hallucinations. People with Type II, or negative
schizophrenia, are usually described as poorly
adjusted before their schizophrenia slowly overtakes
them. They have predominantly ‘‘negative’’ symptoms, such as withdrawal from others and a slowing
of mental and physical reactions (psychomotor
retardation).

Schizophrenia

first-degree biological relatives of schizophrenics are
ten times as likely to develop the disorder as are members of the general population.
Prior to recent findings of abnormalities in the
brain structure of schizophrenic patients, several generations of psychotherapists advanced a number of
psychoanalytic and sociological theories about the
origins of schizophrenia. These theories ranged from
hypotheses about the patient’s problems with anxiety
or aggression to theories about stress reactions or
interactions with disturbed parents. Psychosocial factors are now thought to influence the expression or
severity of schizophrenia rather than cause it directly.
As of 2004, migration is a social factor that is
known to influence people’s susceptibility to psychosis. Psychiatrists in Europe have noted the increasing
rate of schizophrenia and other psychotic disorders
among immigrants to almost all Western European
countries. Black immigrants from Africa or the
Caribbean appear to be especially vulnerable. The
stresses involved in migration include family breakup,
the need to adjust to living in large urban areas, and
social inequalities in the new country.
Another hypothesis suggests that schizophrenia
may be caused by a virus that attacks the hippocampus, a part of the brain that processes sense perceptions. Damage to the hippocampus would account for
schizophrenic patients’ vulnerability to sensory overload. As of 2004, researchers are focusing on the possible role of the herpes simplex virus (HSV) in
schizophrenia, as well as human endogenous retroviruses (HERVs). The possibility that HERVs may
be associated with schizophrenia has to do with the
fact that antibodies to these retroviruses are found
more frequently in the blood serum of patients with
schizophrenia than in serum from control subjects.
Symptoms of schizophrenia
Patients with a possible diagnosis of schizophrenia
are evaluated on the basis of a set or constellation of
symptoms; there is no single symptom that is unique to
schizophrenia. In 1959, the German psychiatrist Kurt
Schneider proposed a list of so-called first-rank symptoms, which he regarded as diagnostic of the disorder.
These symptoms include:


delusions



somatic



hallucinations



hearing voices commenting on the patient’s behavior



thought insertion or thought withdrawal

3302

Somatic hallucinations refer to sensations or perceptions concerning body organs that have no known
medical cause or reason, such as the notion that one’s
brain is radioactive. Thought insertion and/or withdrawal refer to delusions that an outside force (for
example, the FBI, the CIA, Martians, etc.) has the
power to put thoughts into one’s mind or remove
them.
POSITIVE SYMPTOMS. The positive symptoms of
schizophrenia are those that represent an excessive or
distorted version of normal functions. Positive symptoms include Schneider’s first-rank symptoms as well
as disorganized thought processes (reflected mainly in
speech) and disorganized or catatonic behavior.
Disorganized thought processes are marked by such
characteristics as looseness of associations, in which
the patient rambles from topic to topic in a disconnected way; tangentially, which means that the patient
gives unrelated answers to questions; and ‘‘word
salad,’’ in which the patient’s speech is so incoherent
that it makes no grammatical or linguistic sense.
Disorganized behavior means that the patient has difficulty with any type of purposeful or goal-oriented
behavior, including personal self-care or preparing
meals. Other forms of disorganized behavior may
include dressing in odd or inappropriate ways, sexual
self-stimulation in public, or agitated shouting or
cursing.
NEGATIVE SYMPTOMS. Schizophrenia includes
three so-called negative symptoms. They are called
negative because they represent the lack or absence
of behaviors. The negative symptoms that are considered diagnostic of schizophrenia are a lack of emotional response (affective flattening), poverty of
speech, and absence of volition or will. In general,
the negative symptoms are more difficult for doctors
to evaluate than the positive symptoms.

Diagnosis
A doctor must make a diagnosis of schizophrenia
on the basis of a standardized list of outwardly observable symptoms, not on the basis of internal psychological processes. There are no specific laboratory tests
that can be used to diagnose schizophrenia.
Researchers have, however, discovered that patients
with schizophrenia have certain abnormalities in the
structure and functioning of the brain compared to
normal test subjects. These discoveries have been
made with the help of imaging techniques such as
computed tomography scans (CT scans).
When a psychiatrist assesses a patient for schizophrenia, he or she will begin by excluding physical
GALE ENCYCLOPEDIA OF MEDICINE

After ruling out organic disorders, the clinician
will consider other psychiatric conditions that may
include psychotic symptoms or symptoms resembling
psychosis. These disorders include mood disorders
with psychotic features; delusional disorder; dissociative disorder not otherwise specified (DDNOS) or
multiple personality disorder; schizotypal, schizoid, or
paranoid personality disorders; and atypical reactive
disorders. In the past, many individuals were incorrectly diagnosed as schizophrenic. Some patients who
were diagnosed prior to the changes in categorization
should have their diagnoses, and treatment, reevaluated. In children, the doctor must distinguish between
psychotic symptoms and a vivid fantasy life, and also
identify learning problems or disorders. After other
conditions have been ruled out, the patient must meet
a set of criteria specified:


the patient must have two (or more) of the following
symptoms during a one-month period: delusions;
hallucinations; disorganized speech; disorganized or
catatonic behavior; negative symptoms



decline in social, interpersonal, or occupational functioning, including self-care



the disturbed behavior must last for at least six
months



mood disorders, substance abuse disorders, medical
conditions, and developmental disorders have been
ruled out

Treatment
The treatment of schizophrenia depends in part
on the patient’s stage or phase. Psychotic symptoms
and behaviors are considered psychiatric emergencies,
and persons showing signs of psychosis are frequently
taken by family, friends, or the police to a hospital
emergency room. A person diagnosed as psychotic can
be legally hospitalized against his or her will, particularly if he or she is violent, threatening to commit
suicide, or threatening to harm another person. A
psychotic person may also be hospitalized if he or
she has become malnourished or ill as a result of failure to feed, dress appropriately for the climate, or
otherwise take care of him- or herself.
GALE ENCYCLOPEDIA OF MEDICINE

A patient having a first psychotic episode should
be given a CT or MRI (magnetic resonance imaging)
scan to rule out structural brain disease.
Antipsychotic medications
The primary form of treatment of schizophrenia is
antipsychotic medication. Antipsychotic drugs help to
control almost all the positive symptoms of the disorder. They have minimal effects on disorganized
behavior and negative symptoms. Between 60–70%
of schizophrenics will respond to antipsychotics. In
the acute phase of the illness, patients are usually
given medications by mouth or by intramuscular injection. After the patient has been stabilized, the antipsychotic drug may be given in a long-acting form called a
depot dose. Depot medications last for two to four
weeks; they have the advantage of protecting the
patient against the consequences of forgetting or skipping daily doses. In addition, some patients who do
not respond to oral neuroleptics have better results
with depot form. Patients whose long-term treatment
includes depot medications are introduced to the
depot form gradually during their stabilization period.
Most people with schizophrenia are kept indefinitely
on antipsychotic medications during the maintenance
phase of their disorder to minimize the possibility of
relapse.
As of the early 2000s, the most frequently used
antipsychotics fall into two classes: the older dopamine receptor antagonists, or DAs, and the newer
serotonin dopamine antagonists, or SDAs.
(Antagonists block the action of some other substance; for example, dopamine antagonists counteract
the action of dopamine.) The exact mechanisms of
action of these medications are not known, but it is
thought that they lower the patient’s sensitivity to
sensory stimuli and so indirectly improve the patient’s
ability to interact with others.
DOPAMINE RECEPTOR ANTAGONIST. The dopamine antagonists include the older antipsychotic
(also called neuroleptic) drugs, such as haloperidol
(Haldol), chlorpromazine (Thorazine), and fluphenazine (Prolixin). These drugs have two major drawbacks: it is often difficult to find the best dosage level
for the individual patient, and a dosage level high
enough to control psychotic symptoms frequently produces extrapyramidal side effects, or EPS. EPSs
include parkinsonism, in which the patient cannot
walk normally and usually develops a tremor; dystonia, or painful muscle spasms of the head, tongue, or
neck; and akathisia, or restlessness. A type of longterm EPS is called tardive dyskinesia, which features
slow,
rhythmic,
automatic
movements.

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Schizophrenia

conditions that can cause abnormal thinking and some
other behaviors associated with schizophrenia. These
conditions include organic brain disorders (including
traumatic injuries of the brain), temporal lobe epilepsy,
Wilson’s disease, prion diseases, Huntington’s chorea,
and encephalitis. The doctor will also need to rule out
heavy metal poisoning and substance abuse disorders,
especially amphetamine use.

Schizophrenia

Schizophrenics with AIDS are especially vulnerable to
developing EPS.
SEROTONIN DOPANINE ANTAGONISTS. The serotonin dopamine antagonists, also called atypical antipsychotics, are newer medications that include
clozapine (Clozaril), risperidone (Risperdal), and
olanzapine (Zyprexa). The SDAs have a better effect
on the negative symptoms of schizophrenia than do
the older drugs and are less likely to produce EPS than
the older compounds. The newer drugs are significantly more expensive in the short term, although the
SDAs may reduce long-term costs by reducing the
need for hospitalization. They are also presently unavailable in injectable forms. The SDAs are commonly
used to treat patients who respond poorly to the DAs.
However, many psychotherapists now regard the use
of these atypical antipsychotics as the treatment of
first choice; in particular, clozapine appears to be
more effective than other antipsychotics in controlling
persistent aggression in some patients.
NEWER DRUGS. Some newer antipsychotic drugs
have been approved by the Food and Drug administration (FDA) in the early 2000s. These drugs are
sometimes called second-generation antipsychotics or
SGAs. Aripiprazole (Abilify), which is classified as a
partial dopaminergic agonist, received FDA approval
in August 2003. Two drugs that are still under investigation, a neurokinin antagonist and a serotonin 2A/
2C antagonist respectively, show promise in the treatment of schizophrenia and schizoaffective disorder.

strategies is particularly helpful. In addition to formal
treatment, many families benefit from support groups
and similar mutual help organizations for relatives of
schizophrenics.

Prognosis
One important prognostic sign is the patient’s age
at onset of psychotic symptoms. Patients with early
onset of schizophrenia are more often male, have a
lower level of functioning prior to onset, a higher rate
of brain abnormalities, more noticeable negative
symptoms, and worse outcomes. Patients with later
onset are more likely to be female, with fewer brain
abnormalities and thought impairment, and more
hopeful prognoses.
The average course and outcome for schizophrenics are less favorable than those for most other mental disorders, although as many as 30% of patients
diagnosed with schizophrenia recover completely and
the majority experience some improvement. Two factors that influence outcomes are stressful life events
and a hostile or emotionally intense family environment. Schizophrenics with a high number of stressful
changes in their lives, or who have frequent contacts
with critical or emotionally over-involved family
members, are more likely to relapse. Overall, the
most important component of long-term care of schizophrenic patients is complying with their regimen of
antipsychotic medications.
Resources

Psychotherapy
Most schizophrenics can benefit from psychotherapy once their acute symptoms have been brought under
control by antipsychotic medication. Psychoanalytic
approaches are not recommended. Behavior therapy,
however, is often helpful in assisting patients to acquire
skills for daily living and social interaction. It can be
combined with occupational therapy to prepare the
patient for eventual employment.
Family therapy
Family therapy is often recommended for the
families of schizophrenic patients, to relieve the feelings of guilt that they often have as well as to help them
understand the patient’s disorder. The family’s attitude and behaviors toward the patient are key factors
in minimizing relapses (for example, by reducing stress
in the patient’s life), and family therapy can often
strengthen the family’s ability to cope with the stresses
caused by the schizophrenic’s illness. Family therapy
focused on communication skills and problem-solving
3304

BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, D.C.: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychiatric Emergencies.’’ Section 15, Chapter 194 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Schizophrenia and Related Disorders.’’ Section 15,
Chapter 193 In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Wilson, Billie Ann, Margaret T. Shannon, and Carolyn L.
Stang. Nurse’s Drug Guide 2003. Upper Saddle River,
NJ: Prentice Hall, 2003.
PERIODICALS

DeLeon, A., N. C. Patel, and M. L. Crismon. ‘‘Aripiprazole:
A Comprehensive Review of Its Pharmacology, Clinical
Efficacy, and Tolerability.’’ Clinical Therapeutics 26
(May 2004): 649–666.
GALE ENCYCLOPEDIA OF MEDICINE

Affective flattening—A loss or lack of emotional
expressiveness. It is sometimes called blunted or
restricted affect.
Akathisia—Agitated or restless movement, usually
affecting the legs and accompanied by a sense of
discomfort. It is a common side effect of neuroleptic
medications.
Catatonic behavior—Behavior characterized by
muscular tightness or rigidity and lack of response
to the environment. In some patients rigidity alternates with excited or hyperactive behavior.

Huntington’s chorea—A hereditary disease that typically appears in midlife, marked by gradual loss of brain
function and voluntary movement. Some of its symptoms resemble those of schizophrenia.
Negative symptoms—Symptoms of schizophrenia
characterized by the absence or elimination of certain behaviors. DSM-IV specifies three negative
symptoms: affective flattening, poverty of speech,
and loss of will or initiative.
Neuroleptic—Another name for the older type of antipsychotic medications given to schizophrenic patients.

Delusion—A fixed, false belief that is resistant to
reason or factual disproof.
Depot dosage—A form of medication that can be
stored in the patient’s body tissues for several days
or weeks, thus minimizing the risk of the patient
forgetting daily doses. Haloperidol and fluphenazine
can be given in depot form.
Dopamine receptor antagonists (DAs)—The older
class of antipsychotic medications, also called neuroleptics. These primarily block the site on nerve cells
that normally receive the brain chemical dopamine.
Dystonia—Painful involuntary muscle cramps or
spasms.

Parkinsonism—A set of symptoms originally associated with Parkinson disease that can occur as side
effects of neuroleptic medications. The symptoms
include trembling of the fingers or hands, a shuffling
gait, and tight or rigid muscles.
Positive symptoms—Symptoms of schizophrenia
that are characterized by the production or presence
of behaviors that are grossly abnormal or excessive,
including hallucinations and thought-process disorder. DSM-IV subdivides positive symptoms into psychotic and disorganized.
Poverty of speech—A negative symptom of schizophrenia, characterized by brief and empty replies to
questions. It should not be confused with shyness or
reluctance to talk.

Extrapyramidal symptoms (EPS)—A group of side
effects associated with antipsychotic medications.
EPS include parkinsonism, akathisia, dystonia, and
tardive dyskinesia.
First-rank symptoms—A set of symptoms designated
by Kurt Schneider in 1959 as the most important diagnostic indicators of schizophrenia. These symptoms
include delusions, hallucinations, thought insertion or
removal, and thought broadcasting. First-rank symptoms
are sometimes referred to as Schneiderian symptoms.
Hallucination—A sensory experience of something
that does not exist outside the mind. A person can
experience a hallucination in any of the five senses.
Auditory hallucinations are a common symptom of
schizophrenia.

Psychotic disorder—A mental disorder characterized by delusions, hallucinations, or other symptoms
of lack of contact with reality. The schizophrenias are
psychotic disorders.
Serotonin dopamine antagonist (SDA)—The newer
second-generation antipsychotic drugs, also called atypical antipsychotics. SDAs include clozapine (Clozaril),
risperidone (Risperdal), and olanzapine (Zyprexa).
Wilson disease—A rare hereditary disease marked by
high levels of copper deposits in the brain and liver. It can
cause psychiatric symptoms resembling schizophrenia.

Frankenburg, Frances R., MD. ‘‘Schizophrenia.’’ eMedicine
June 17, 2004. <http://www.emedicine.com/med/
topic2072.htm>.
Hutchinson, G., and C. Haasen. ‘‘Migration and
Schizophrenia: The Challenges for European Psychiatry
and Implications for the Future.’’ Social Psychiatry and
Psychiatric Epidemiology 39 (May 2004): 350–357.

Meltzer, H. Y., L. Arvanitis, D. Bauer, et al. ‘‘PlaceboControlled Evaluation of Four Novel Compounds for
the Treatment of Schizophrenia and Schizoaffective
Disorder.’’ American Journal of Psychiatry 161 (June
2004): 975–984.
Mueser, K. T., and S. R. McGurk. ‘‘Schizophrenia.’’ Lancet
363 (June 19, 2004): 2063–2072.

GALE ENCYCLOPEDIA OF MEDICINE

Word salad—Speech that is so disorganized that it
makes no linguistic or grammatical sense.

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Schizophrenia

KEY TERMS

Sciatica

Volavka, J., P. Czobor, K. Nolan, et al. ‘‘Overt Aggression
and Psychotic Symptoms in Patients with
Schizophrenia Treated with Clozapine, Olanzapine,
Risperidone, or Haloperidol.’’ Journal of Clinical
Psychopharmacology 24 (April 2004): 225–228.
Yolken, R. ‘‘Viruses and Schizophrenia: A Focus on Herpes
Simplex Virus.’’ Herpes 11, Supplement 2 (June 2004):
83A–88A.

originates in the lower part of the spinal cord, the socalled lumbar region. As it branches off from the
spinal cord, it passes between the bony vertebrae (the
component bones of the spine) and runs through
the pelvic girdle, or hip bones. The nerve passes
through the hip joint and continues down the back
of the leg to the foot.

ORGANIZATIONS

Sciatica is a fairly common disorder and approximately 40% of the population experiences it at some
point in their lives. However, only about 1% have
coexisting sensory or motor deficits. Sciatic pain has
several root causes and treatment may hinge upon the
underlying problem.

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924.
<http://www.psych.org>.
National Alliance for the Mentally Ill (NAMI). Colonial
Place Three, 2107 Wilson Blvd., Suite 300 Arlington,
VA 22201. (703) 524-7600 HelpLine: (800) 950-NAMI.
<http://www.nami.org/>.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513.
<http://www.nimh.nih.gov>.
Schizophrenics Anonymous. 15920 W. Twelve Mile,
Southfield, MI 48076. (248) 477-1983.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <http://www.fda.gov>.
OTHER

‘‘Schizophrenia.’’ Internet Mental Health. <http://
www.mentalhealth.com/dis/p20-ps01.html>.

Laith Farid Gulli, M.D.
Rebecca Frey, PhD

Schwannoma see Brain tumor
Sciatic nerve pain see Sciatica

Sciatica
Definition
Sciatica refers to pain or discomfort associated
with the sciatic nerve. This nerve runs from the lower
part of the spinal cord, down the back of the leg, to the
foot. Injury to or pressure on the sciatic nerve can
cause the characteristic pain of sciatica: a sharp or
burning pain that radiates from the lower back or
hip, possibly following the path of the sciatic nerve
to the foot.

Of the identifiable causes of sciatic pain, lumbosacral radiculopathy and back strain are the most
frequently suspected. The term lumbosacral refers to
the lower part of the spine, and radiculopathy
describes a problem with the spinal nerve roots that
pass between the vertebrae and give rise to the sciatic
nerve. This area between the vertebrae is cushioned
with a disk of shock- absorbing tissue. If this disk
shifts or is damaged through injury or disease, the
spinal nerve root may be compressed by the shifted
tissue or the vertebrae.
This compression of the nerve roots sends a pain
signal to the brain. Although the actual injury is to the
nerve roots, the pain may be perceived as coming from
anywhere along the sciatic nerve.
The sciatic nerve can be compressed in other ways.
Back strain may cause muscle spasms in the lower
back, placing pressure on the sciatic nerve. In rare
cases, infection, cancer, bone inflammation, or other
diseases may be causing the pressure. More likely, but
often overlooked, is the piriformis syndrome. As the
sciatic nerve passes through the hip joint, it shares
the space with several muscles. One of these muscles,
the piriformis muscle, is closely associated with the
sciatic nerve. In some people, the nerve actually runs
through the muscle. If this muscle is injured or has a
spasm, it places pressure on the sciatic nerve, in effect,
compressing it.
In many sciatica cases, the specific cause is never
identified. About half of affected individuals recover
from an episode within a month. Some cases can linger
a few weeks longer and may require aggressive treatment. In some cases, the pain may return or potentially become chronic.

Description
The sciatic nerve is the largest and longest nerve in
the body. About the thickness of a person’s thumb, it
spans from the lower back to the foot. The nerve
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Causes and symptoms
Individuals with sciatica may experience some
lower back pain, but the most common symptom is
GALE ENCYCLOPEDIA OF MEDICINE

Onset of sciatica can be sudden, but it can also
develop gradually. The pain may be intermittent or
continuous, and certain activities, such as bending,
coughing, sneezing, or sitting, may make the pain worse.
Chronic pain may arise from more than just
compression on the nerve. According to some pain
researchers, physical damage to a nerve is only half of
the equation. A developing theory proposes that some
nerve injuries result in a release of neurotransmitters
and immune system chemicals that enhance and sustain
a pain message. Even after the injury has healed, or the
damage has been repaired, the pain continues. Control
of this abnormal type of pain is difficult.

Diagnosis
Before treating sciatic pain, as much information
as possible is collected. The individual is asked to
recount the location and nature of the pain, how
long it has continued, and any accidents or unusual
activities prior to its onset. This information provides
clues that may point to back strain or injury to a
specific location. Back pain from disk disease, piriformis syndrome, and back strain must be differentiated
from more serious conditions such as cancer or infection. Lumbar stenosis, an overgrowth of the covering
layers of the vertebrae that narrows the spinal canal,
must also be considered. The possibility that a difference in leg lengths is causing the pain should be evaluated; the problem can be easily be treated with a foot
orthotic or built-up shoe.
Often, a straight-leg-raising test is done, in which
the person lies face upward and the health-care provider raises the affected leg to various heights. This test
pinpoints the location of the pain and may reveal
whether it is caused by a disk problem. Other tests,
such as having the individual rotate the hip joint,
assess the hip muscles. Any pain caused by these
movements may provide information about involvement of the piriformis muscle, and piriformis weakness is tested with additional leg-strength maneuvers.
Further tests may be done depending on the results
of the physical examination and initial pain treatment.
Such tests might include magnetic resonance imaging
GALE ENCYCLOPEDIA OF MEDICINE

(MRI) and computed tomography scans (CT scans).
Other tests examine the conduction of electricity
through nerve tissues, and include studies of the electrical activity generated as muscles contract (electromyography), nerve conduction velocity, and evoked
potential testing. A more invasive test involves injecting
a contrast substance into the space between the vertebrae and making x-ray images of the spinal cord (myelography), but this procedure is usually done only if
surgery is being considered. All of these tests can reveal
problems with the vertebrae, the disk, or the nerve itself.

Treatment
Initial treatment for sciatica focuses on pain relief.
For acute or very painful flare-ups, bed rest is advised
for up to a week in conjunction with medication for
the pain. Pain medication includes acetaminophen,
nonsteroidal anti-inflammatory drugs (NSAIDs), such
as aspirin, or muscle relaxants. If the pain is unremitting, opioids may be prescribed for short-term use or a
local anesthetic will be injected directly into the lower
back. Massage and heat application may be suggested
as adjuncts.
If the pain is chronic, different pain relief medications are used to avoid long-term dosing of NSAIDs,
muscle relaxants, and opioids. Antidepressant drugs,
which have been shown to be effective in treating pain,
may be prescribed alongside short-term use of muscle
relaxants or NSAIDs. Local anesthetic injections or
epidural steroids are used in selected cases.
As the pain allows, physical therapy is introduced
into the treatment regime. Stretching exercises that
focus on the lower back, buttock, and hamstring muscles are suggested. The exercises also include finding
comfortable, pain-reducing positions. Corsets and
braces may be useful in some cases, but evidence for
their general effectiveness is lacking. However, they
may be helpful to prevent exacerbations related to
certain activities.
With less pain and the success of early therapy, the
individual is encouraged to follow a long-term program
to maintain a healthy back and prevent re-injury. A
physical therapist may suggest exercises and regular
activity, such as water exercise or walking. Patients
are instructed in proper body mechanics to minimize
symptoms during light lifting or other activities.
If the pain is chronic and conservative treatment
fails, surgery to repair a herniated disk or cut out part
or all of the piriformis muscle may be suggested, particularly if there is neurologic evidence of nerve or
nerve-root damage.
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Sciatica

pain that radiates through one buttock and down the
back of that leg. The most identified cause of the pain
is compression or pressure on the sciatic nerve. The
extent of the pain varies between individuals. Some
people describe pain that centers in the area of the hip,
and others perceive discomfort all the way to the foot.
The quality of the pain also varies; it may be described
as tingling, burning, prickly, aching, or stabbing.

Scleroderma

KEY TERMS
Disk—Dense tissue between the vertebrae that acts
as a shock absorber and prevents damage to nerves
and blood vessels along the spine.
Electromyography—A medical test in which a
nerve’s ability to conduct an impulse is measured.
Lumbosacral—Referring to the lower part of the
backbone or spine.
Myelography—A medical test in which a special dye
is injected into a nerve to make it visible on an x ray.
Piriformis—A muscle in the pelvic girdle that is
closely associated with the sciatic nerve.
Radiculopathy—A condition in which the spinal
nerve root of a nerve has been injured or damaged.
Spasm—Involuntary contraction of a muscle.
Vertebrae—The component bones of the spine.

General suggestions for avoiding sciatica, or preventing a repeat episode, include sleeping on a firm
mattress, using chairs with firm back support, and
sitting with both feet flat on the floor. Habitually
crossing the legs while sitting can place excess pressure
on the sciatic nerve. Sitting a lot can also place pressure on the sciatic nerves, so it’s a good idea to take
short breaks and move around during the work day,
long trips, or any other situation that requires sitting
for an extended length of time. If lifting is required, the
back should be kept straight and the legs should provide the lift. Regular exercise, such as swimming and
walking, can strengthen back muscles and improve
posture. Exercise can also help maintain a healthy
weight and lessen the likelihood of back strain.
Resources
PERIODICALS

Douglas, Sara. ‘‘Sciatic Pain and Piriformis Syndrome.’’
The Nurse Practitioner 22 (May 1997): 166.

Julia Barrett

Alternative treatment
Massage is a recommended form of therapy, especially if the sciatic pain arises from muscle spasm.
Symptoms may also be relieved by icing the painful
area as soon as the pain occurs. Ice should be left on
the area for 30-60 minutes several times a day. After 23 days, a hot water bottle or heating pad can replace
the ice. Chiropractic or osteopathy may offer possible
solutions for relieving pressure on the sciatic nerve and
the accompanying pain. Acupuncture and biofeedback
may also be useful as pain control methods. Body
work, such as the Alexander technique, can assist an
individual in improving posture and preventing
further episodes of sciatic pain.

Prognosis
Most cases of sciatica are treatable with pain
medication and physical therapy. After 4-6 weeks of
treatment, an individual should be able to resume
normal activities.

Prevention
Some sources of sciatica are not preventable, such
as disk degeneration, back strain due to pregnancy, or
accidental falls. Other sources of back strain, such as
poor posture, overexertion, being overweight, or
wearing high heels, can be corrected or avoided.
Cigarette smoking may also predispose people to
pain, and should be discontinued.
3308

SCID see Severe combined
immunodeficiency
Scleral buckling see Retinal detachment

Scleroderma
Definition
Scleroderma is a progressive disease that affects the
skin and connective tissue (including cartilage, bone, fat,
and the tissue that supports the nerves and blood vessels
throughout the body). There are two major forms of
the disorder. The type known as localized scleroderma
mainly affects the skin. Systemic scleroderma, which is
also called systemic sclerosis, affects the smaller blood
vessels and internal organs of the body.

Description
Scleroderma is an autoimmune disorder, which
means that the body’s immune system turns against
itself. In scleroderma, there is an overproduction
of abnormal collagen (a type of protein fiber present
in connective tissue). This collagen accumulates
throughout the body, causing hardening (sclerosis),
scarring (fibrosis), and other damage. The damage
may affect the appearance of the skin, or it may involve
only the internal organs. The symptoms and severity of
scleroderma vary from person to person.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The cause of scleroderma is still a puzzle. Although
the accumulation of collagen appears to be a hallmark
of the disease, researchers do not know why it occurs.
Some theories suggest that damage to blood vessels
may cause the tissues of the body to receive an inadequate amount of oxygen—a condition called ischemia.
Some researchers believe that the resulting damage
causes the immune system to overreact, producing an
autoimmune disorder. According to this theory of
scleroderma, the immune system gears up to fight an
invader, but no invader is actually present. Cells in the
immune system called antibodies react to the body’s
own tissues as if they were foreign. The antibodies
turn against the already damaged blood vessels and
the vessels’ supporting tissues. These immune cells are
designed to deliver potent chemicals in order to kill
foreign invaders. Some of these cells dump these
chemicals on the body’s own tissues instead, causing
inflammation, swelling, damage, and scarring.
Most cases of scleroderma have no recognizable
triggering event. Some cases, however, have been traced
to exposure to toxic (poisonous) substances. For example, coal miners and gold miners, who are exposed to
high levels of silica dust, have above-average rates of
scleroderma. Other chemicals associated with the disease include polyvinyl chloride, benzine, toluene, and
epoxy resins. In 1981, 20,000 people in Spain were
stricken with a syndrome similar to scleroderma when
their cooking oil was accidentally contaminated.
Certain medications, especially a drug used in cancer
treatment called bleomycin (Blenoxane), may lead to
scleroderma. Some claims of a scleroderma-like illness
have been made by women with silicone breast implants,
but a link has not been proven in numerous studies.
Symptoms of systemic scleroderma
A condition called Raynaud’s phenomenon is the
first symptom in about 95% of all patients with
GALE ENCYCLOPEDIA OF MEDICINE

systemic scleroderma. In Raynaud’s phenomenon, the
blood vessels of the fingers and/or toes (the digits) react
to cold in an abnormal way. The vessels clamp down,
preventing blood flow to the tip of the digit. Eventually,
the flow is cut off to the entire finger or toe. Over time,
oxygen deprivation may result in open ulcers on
the skin surface. These ulcers can lead to tissue death
(gangrene) and loss of the digit. When Raynaud’s
phenomenon is the first sign of scleroderma, the next
symptoms usually appear within two years.
SKIN AND EXTREMITIES. Involvement of the skin
leads to swelling underneath the skin of the hands,
feet, legs, arms, and face. Swelling is followed by thickening and tightening of the skin, which becomes taut
and shiny. Severe tightening may lead to abnormalities.
For example, tightening of the skin on the hands may
cause the fingers to become permanently curled (flexed).
Structures within the skin are damaged (including those
producing hair, oil, and sweat), and the skin becomes
dry and scaly. Ulcers may form, with the danger of
infection. Calcium deposits often appear under the skin.

In systemic scleroderma, the mouth and nose may
become smaller as the skin on the face tightens. The
small mouth may interfere with eating and dental
hygiene. Blood vessels under the skin may become
enlarged and show through the skin, appearing as
purplish marks or red spots. This chronic dilation of
the small blood vessels is called telangiectasis.
Muscle weakness, joint pain and stiffness, and
carpal tunnel syndrome are common in scleroderma.
Carpal tunnel syndrome involves scarring in the wrist,
which puts pressure on the median nerve running
through that area. Pressure on the nerve causes numbness, tingling, and weakness in some of the fingers.
DIGESTIVE TRACT. The tube leading from the
mouth to the stomach (the esophagus) becomes stiff
and scarred. Patients may have trouble swallowing
food. The acid contents of the stomach may start to
flow backward into the esophagus (esophageal reflux),
causing a very uncomfortable condition known as
heartburn. The esophagus may also become inflamed.

The intestine becomes sluggish in processing food,
causing bloating and pain. Foods are not digested
properly, resulting in diarrhea, weight loss, and anemia. Telangiectasis in the stomach or intestine may
cause rupture and bleeding.
RESPIRATORY AND CIRCULATORY SYSTEMS. The
lungs are affected in about 66% of all people with
systemic scleroderma. Complications include shortness of breath, coughing, difficulty breathing due to
tightening of the tissue around the chest, inflammation
of the air sacs in the lungs (alveolitis), increased risk of

3309

Scleroderma

Scleroderma occurs in all races of people all over
the world, but it affects about four females for every
male. Among children, localized scleroderma is more
common, and systemic sclerosis is comparatively rare.
Most patients with systemic sclerosis are diagnosed
between ages 30 and 50. In the United States, about
300,000 people have scleroderma. Young AfricanAmerican women and Native Americans of the
Choctaw tribe have especially high rates of the disease.
In 2003, researchers reported that they had identified
12 different genetic markers associated with scleroderma in the Choctaw population.

Scleroderma

course of a physical examination. The person’s medical
history may also contain important clues, such as exposure to toxic substances on the job. There are a number
of nonspecific laboratory tests on blood samples that
may indicate the presence of an inflammatory disorder
(but not specifically scleroderma). The antinuclear antibody (ANA) test is positive in more than 95% of people
with scleroderma.

Scleroderma is a serious, progressive disease caused by the
overproduction and accumulation of collagen throughout the
body, resulting in hardening (sclerosis) and scarring (fibrosis) of the skin and connective tissue. (Photo Researchers, Inc.
Reproduced by permission.)

pneumonia, and an increased risk of cancer. For these
reasons, lung disease is the most likely cause of death
associated with scleroderma.
The lining around the heart (pericardium) may
become inflamed. The heart may have greater difficulty
pumping blood effectively (heart failure). Irregular
heart rhythms and enlargement of the heart also occur
in scleroderma.
Kidney disease is another common complication.
Damage to blood vessels in the kidneys often causes a
major rise in the person’s blood pressure. The blood
pressure may be so high that there is swelling of the
brain, causing severe headaches, damage to the retinas
of the eyes, seizures, and failure of the heart to pump
blood into the body’s circulatory system. The kidneys
may also stop filtering blood and go into failure.
Treatments for high blood pressure have greatly
improved these kidney complications. Before these treatments were available, kidney problems were the most
common cause of death for people with scleroderma.
Other problems associated with scleroderma
include painful dryness of the eyes and mouth, enlargement and destruction of the liver, and a low-functioning
thyroid gland.

Diagnosis
Diagnosis of scleroderma is complicated by the
fact that some of its symptoms can accompany other
connective-tissue diseases. The most important symptom is thickened or hardened skin on the fingers, hands,
forearms, or face. This symptom is found in 98% of
people with scleroderma. It can be detected in the
3310

Other tests can be performed to evaluate the
extent of the disease. These include a test of the
electrical system of the heart (an electrocardiogram),
lung-function tests, and x-ray studies of the gastrointestinal tract. Various blood tests can be given to
study kidney function.

Treatment
Mainstream treatments
As of early 2004 there is no cure for scleroderma.
A drug called D-penicillamine has been used to interfere with the abnormal collagen. It is believed to help
decrease the degree of skin thickening and tightening,
and to slow the progress of the disease in other organs.
Taking vitamin D and using ultraviolet light may be
helpful for localized scleroderma. One group of British
researchers reported in 2003 that long-wavelength
ultraviolet A light is particularly effective in treating
localized scleroderma. Corticosteroids have been used
to treat joint pain, muscle cramps, and other symptoms
of inflammation. Other drugs have been studied that
reduce the activity of the immune system (immunosuppressants). Because these medications can have
serious side effects, they are used in only the most
severe cases of scleroderma.
The various complications of scleroderma are
treated individually. Raynaud’s phenomenon requires
that people try to keep their hands and feet warm
constantly. Nifedipine is a medication that is sometimes given to help control Raynaud’s. Thick ointments and creams are used to treat dry skin. Exercise
and massage may help joint involvement; they may
also help people retain more movement despite skin
tightening. An exercise regimen for stretching the
mouth opening has been reported to be a helpful
alternative to surgery in managing this condition.
Skin ulcers need prompt attention and may require
antibiotics. People with esophageal reflux will be
advised to eat small amounts more often, rather than
several large meals a day. They should also avoid spicy
foods and items containing caffeine. Some patients
with esophageal reflux have been successfully treated
with surgery. Acid-reducing medications may be given
GALE ENCYCLOPEDIA OF MEDICINE

Patients with scleroderma may also benefit from
some form of counseling or psychotherapy, as they are
at increased risk of depression. One study found that
46% of the patients in its sample met the criteria for a
depressive disorder.
Alternative treatments
One alternative therapy that some naturopaths
have used in treating patients with scleroderma is
superoxide dismutase (SOD), an antioxidant enzyme
used in its injectable form. More research, however,
needs to be done on the benefits of this treatment.

Prognosis
The prognosis for people with scleroderma varies.
Some have a very limited form of the disease called
morphea, which affects only the skin. These individuals
have a very good prognosis. Other people have a subtype of systemic scleroderma called limited scleroderma. For them, the prognosis is relatively good.
Limited scleroderma is characterized by limited involvement of the patient’s skin and a cluster of five symptoms called the CREST syndrome. CREST stands for:


C=Calcinosis



R=Raynaud’s disease (phenomenon)



E=Esophageal dysmotility (stiffness and malfunctioning of the esophagus)



S=Sclerodactyly (thick, hard, rigid skin over the
fingers)



T=Telangiectasias

In general, people with very widespread skin
involvement have the worst prognosis. This level of
disease is usually accompanied by involvement of
other organs and the most severe complications.
Although women are more commonly stricken
with scleroderma, men more often die of the disease.
The two factors that negatively affect survival are male
sex and older age at diagnosis. The most common
causes of death include heart, kidney, and lung diseases. About 65% of all patients survive 11 years or
more following a diagnosis of scleroderma.
As of early 2004 there are no known ways to
prevent scleroderma. People can try to decrease occupational exposure to high-risk substances.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Autoimmune disorder—A disorder in which the
body’s immune cells mistake the body’s own tissues as foreign invaders; the immune cells then
work to destroy tissues in the body.
Collagen—The main supportive protein of cartilage, connective tissue, tendon, skin, and bone.
Connective tissue—A group of tissues responsible
for support throughout the body; includes cartilage,
bone, fat, tissue underlying skin, and tissues that
support organs, blood vessels, and nerves throughout the body.
Fibrosis—The abnormal development of fibrous
tissue; scarring.
Limited scleroderma—A subtype of systemic scleroderma with limited skin involvement. It is somestimes called the CREST form of scleroderma, after
the initials of its five major symptoms.
Localized scleroderma—Thickening of the skin
from overproduction of collagen.
Morphea—The most common form of localized
scleroderma.
Raynaud phenomenon/Raynaud disease—A condition in which blood flow to the body’s tissues is
reduced by a malfunction of the nerves that regulate the constriction of blood vessels. When attacks
of Raynaud’s occur in the absence of other medical
conditions, it is called Raynaud disease. When
attacks occur as part of a disease (as in scleroderma), it is called Raynaud phenomenon.
Sclerosis—Hardening.
Systemic sclerosis—A rare disorder that causes
thickening and scarring of multiple organ systems.
Telangiectasias—Very small arteriovenous malformations, or connections between the arteries and
veins. The result is small red spots on the skin
known as ‘‘spider veins.’’

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Systemic Sclerosis.’’ The Merck Manual of Diagnosis
and Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine,
Part II: CAM Therapies for Specific Conditions:
Scleroderma. New York: Simon and Schuster, 2002.
3311

Scleroderma

for heartburn. People must be monitored for the development of high blood pressure. If found, they should
be promptly treated with appropriate medications,
usually ACE inhibitors or other vasodilators. When
fluid accumulates due to heart failure, diuretics can
be given to get rid of the excess fluid.

Sclerotherapy for esophageal varices

Purpose

PERIODICALS

Dawe, R. S. ‘‘Ultraviolet A1 Phototherapy.’’ British Journal
of Dermatology 148 (April 2003): 626–637.
Hill, C. L., A. M. Nguyen, D. Roder, and P. RobertsThomson. ‘‘Risk of Cancer in Patients with
Scleroderma: A Population Based Cohort Study.’’
Annals of the Rheumatic Diseases 62 (August 2003):
728–731.
Matsuura, E., A. Ohta, F. Kanegae, et al. ‘‘Frequency and
Analysis of Factors Closely Associated with the
Development of Depressive Symptoms in Patients with
Scleroderma.’’ Journal of Rheumatology 30 (August
2003): 1782–1787.
Mayes, M. D., J. V. Lacey, Jr., J. Beebe-Dimmer, et al.
‘‘Prevalence, Incidence, Survival, and Disease
Characteristics of Systemic Sclerosis in a Large US
Population.’’ Arthritis and Rheumatism 48 (August
2003): 2246–2255.
Pizzo, G., G. A. Scardina, and P. Messina. ‘‘Effects of a
Nonsurgical Exercise Program on the Decreased
Mouth Opening in Patients with Systemic
Scleroderma.’’ Clinical Oral Investigations 7 (September
2003): 175–178.
Zhou, X., F. K. Tan, N. Wang, et al. ‘‘Genome-Wide
Association Study for Regions of Systemic Sclerosis
Susceptibility in a Choctaw Indian Population with
High Disease Prevalence.’’ Arthritis and Rheumatism 48
(September 2003): 2585–2592.
ORGANIZATIONS

American College of Rheumatology. 60 Executive Park
South, Suite 150, Atlanta, GA 30329. (404) 633-3777.
<http://www.rheumatology.org>.
National Organization for Rare Disorders, Inc. (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813.
(800) 999-6673 or (203) 744-0100. <http://
www.rarediseases.org>.
Scleroderma Foundation. 12 Kent Way, Suite 101, Byfield,
MA 01922. (978) 463-5843 or (800) 722-HOPE. Fax:
(978) 463-5809. <http://www.scleroderma.org.>.

Rebecca J. Frey, PhD

Sclerotherapy for esophageal
varices

Definition
Sclerotherapy for esophageal varices (also called
endoscopic sclerotherapy) is a treatment for esophageal bleeding that involves the use of an endoscope
and the injection of a sclerosing solution into veins.
3312

In most hospitals, sclerotherapy for esophageal
varices is the treatment of choice to stop esophageal
bleeding during acute episodes, and to prevent further
incidences of bleeding. Emergency sclerotherapy is
often followed by preventive treatments to eradicate
distended esophageal veins.

Precautions
Sclerotherapy for esophageal varices cannot be
performed on an uncooperative patient, since movement during the procedure could cause the vein to tear
or the esophagus to perforate and bleed. It should not
be performed on a patient with a perforated gastrointestinal tract.

Description
Esophageal varices are enlarged or swollen veins
on the lining of the esophagus which are prone to
bleeding. They are life-threatening, and can be fatal
in up to 50% of patients. They usually appear in
patients with severe liver disease. Sclerotherapy for
esophageal varices involves injecting a strong and irritating solution (a sclerosant) into the veins and/or the
area beside the distended vein. The sclerosant injected
into the vein causes blood clots to form and stops the
bleeding. The sclerosant injected into the area beside
the distended vein stops the bleeding by thickening
and swelling the vein to compress the blood vessel.
Most physicians inject the sclerosant directly into the
vein, although injections into the vein and the surrounding area are both effective. Once bleeding has
been stopped, the treatment can be used to significantly reduce or destroy the varices.
Sclerotherapy for esophageal varices is performed
by a physician in a hospital, with the patient awake but
sedated. Hyoscine butylbromide (Buscopan) may be
administered to freeze the esophagus, making injection of the sclerosant easier. During the procedure, an
endoscope is passed through the patient’s mouth to
the esophagus to view the inside. The branches of the
blood vessels at or just above where the stomach and
esophagus come together, the usual site of variceal
bleeding, are located. After the bleeding vein is identified, a long, flexible sclerotherapy needle is passed
through the endoscope. When the tip of the needle’s
sheath is in place, the needle is advanced, and the
sclerosant is injected into the vein or the surrounding
area. The most commonly used sclerosants are ethanolamine and sodium tetradecyl sulfate. The needle is
withdrawn. The procedure is repeated as many times
as necessary to eradicate all distended veins.
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
Before sclerotherapy for esophageal varices, the
patient’s vital signs and other pertinent data are
recorded, an intravenous line is inserted to administer
fluid or blood, and a sedative is prescribed.

Aftercare
After sclerotherapy for esophageal varices, the
patient will be observed for signs of blood loss, lung
complications, fever, a perforated esophagus, or other
complications. Vital signs are monitored, and the
intravenous line maintained. Pain medication is
usually prescribed. After leaving the hospital, the
patient follows a diet prescribed by the physician,
and, if appropriate, can take mild pain relievers.

KEY TERMS
Endoscope—An instrument used to examine the
inside of a canal or hollow organ. Endoscopic surgery is less invasive than traditional surgery.
Esophagus—The part of the digestive canal located
between the pharynx (part of the digestive tube)
and the stomach.
Sclerosant—An irritating solution that stops bleeding by hardening the blood or vein it is injected
into.
Varices—Swollen or enlarged veins, in this case on
the lining of the esophagus.

hepatic coma. The blood in the bowels acts like a high
protein meal; therefore, protein intoxication may be
induced.
Resources
PERIODICALS

Cello, J. P. ‘‘Endoscopic Management of Esophageal
VaricealHemorrhage: Injection, Banding, Glue,
Octreotide, or a Combination?’’ Seminars in
Gastrointestinal Diseases 8 (October 1997): 179-187.

Lori De Milto

Risks
Sclerotherapy for esophageal varices has a 2040% incidence of complications, and a 1–2% percent
mortality rate. Complications can arise from the sclerosant or the endoscopic procedure. Minor complications, which are uncomfortable but do not require
active treatment or prolonged hospitalization, include
transient chest pain, difficulty swallowing, and fever,
which usually go away after a few days. Some people
have allergic reactions to the solution. Infection occurs
in up to 50% of cases. In 2-10% of patients, the
esophagus tightens, but this can usually be treated
with dilatation. More serious complications may
occur in 10-15% of patients treated with sclerotherapy. These include perforation or bleeding of the esophagus and lung problems, such as aspiration
pneumonia. Long-term sclerotherapy can damage the
esophagus, and increase the patient’s risk of developing cancer.
Patients with advanced liver disease complicated
by bleeding are very poor risks for this procedure. The
surgery, premedications, and anesthesia may be sufficient to tip the patient into protein intoxication and
GALE ENCYCLOPEDIA OF MEDICINE

Scoliosis
Definition
Scoliosis is a side-to-side curvature of the spine.

Description
When viewed from the rear, the spine usually
appears perfectly straight. Scoliosis is a lateral (sideto-side) curve in the spine, usually combined with a
rotation of the vertebrae. (The lateral curvature of
scoliosis should not be confused with the normal set
of front-to-back spinal curves visible from the side.)
While a small degree of lateral curvature does not
cause any medical problems, larger curves can cause
postural imbalance and lead to muscle fatigue and
pain. More severe scoliosis can interfere with breathing and lead to arthritis of the spine (spondylosis).
3313

Scoliosis

Sclerotherapy for esophageal varices controls
acute bleeding in about 90% of patients, but it may
have to be repeated within the first 48 hours to achieve
this success rate. During the initial hospitalization,
sclerotherapy is usually performed two or three
times. Preventive treatments are scheduled every few
weeks or so, depending on the patient’s risk level and
healing rate. Several studies have shown that the risk
of recurrent bleeding is much lower in patients treated
with sclerotherapy: 30-50%, as opposed to 70-80% for
patients not treated with sclerotherapy.

Scoliosis

Approximately 10% of all adolescents have some
degree of scoliosis, though fewer than 1% have curves
which require medical attention beyond monitoring.
Scoliosis is found in both boys and girls, but a girl’s
spinal curve is much more likely to progress than a
boy’s. Girls require scoliosis treatment about five
times as often. The reason for these differences is not
known.

Causes and symptoms
Four out of five cases of scoliosis are idiopathic,
meaning the cause is unknown. While idiopathic scoliosis tends to run in families, no responsible genes had
been identified as of 1997. Children with idiopathic
scoliosis appear to be otherwise entirely healthy, and
have not had any bone or joint disease early in life.
Scoliosis is not caused by poor posture, diet, or carrying a heavy bookbag exclusively on one shoulder.
Idiopathic scoliosis is further classified according
to age of onset:


Infantile. Curvature appears before age three. This
type is quite rare in the United States, but is more
common in Europe.



Juvenile. Curvature appears between ages 3 and 10.
This type may be equivalent to the adolescent type,
except for the age of onset.



Adolescent. Curvature appears between ages of 10
and 13, near the beginning of puberty. This is the
most common type of idiopathic scoliosis.



Adult. Curvature begins after physical maturation is
completed.

Causes are known for three other types of
scoliosis:




Congenital scoliosis is due to congenital abnormal
formation of the bones of the spine, and is often
associated with other organ defects.
Neuromuscular scoliosis is due to loss of control of
the nerves or muscles which support the spine. The
most common causes of this type of scoliosis are
cerebral palsy and muscular dystrophy.

appear more prominent than the other due to rotation.
In girls, one breast may appear higher than the other,
or larger if rotation pushes that side forward.
Curve progression is greatest near the adolescent
growth spurt. Scoliosis that begins early on is more
likely to progress significantly than scoliosis that
begins later in puberty.
More than 30 states have screening programs in
schools for adolescent scoliosis, usually conducted by
trained school nurses or gym teachers.

Diagnosis
Diagnosis for scoliosis is done by an orthopedist.
A complete medical history is taken, including questions about family history of scoliosis. The physical
examination includes determination of pubertal development in adolescents, a neurological exam (which
may reveal a neuromuscular cause), and measurements of trunk asymmetry. Examination of the trunk
is done while the patient is standing, bending over, and
lying down, and involves both visual inspection and
use of a simple mechanical device called a scoliometer.
If a curve is detected, one or more x rays will
usually be taken to define the curve or curves more
precisely. An x ray is used to document spinal maturity, any pelvic tilt or hip asymmetry, and the location,
extent, and degree of curvature. The curve is defined in
terms of where it begins and ends, in which direction it
bends, and by an angle measure known as the Cobb
angle. The Cobb angle is found by projecting lines
parallel to the vertebrae tops at the extremes of the
curve; projecting perpendiculars from these lines; and
measuring the angle of intersection. To properly track
the progress of scoliosis, it is important to project from
the same points of the spine each time.
Occasionally, magnetic resonance imaging (MRI)
is used, primarily to look more closely at the condition
of the spinal cord and nerve roots extending from it if
neurological problems are suspected.

Treatment

Degenerative scoliosis may be caused by degeneration of the discs which separate the vertebrae or
arthritis in the joints that link them.

Treatment decisions for scoliosis are based on the
degree of curvature, the likelihood of significant progression, and the presence of pain, if any.

Scoliosis causes a noticeable asymmetry in the
torso when viewed from the front or back. The first
sign of scoliosis is often seen when a child is wearing a
bathing suit or underwear. A child may appear to be
standing with one shoulder higher than the other, or to
have a tilt in the waistline. One shoulder blade may

Curves less than 20 degrees are not usually treated, except by regular follow-up for children who are
still growing. Watchful waiting is usually all that is
required in adolescents with curves of 20–30 degrees,
or adults with curves up to 40 degrees or slightly more,
as long as there is no pain.



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Surgery for idiopathic scoliosis is usually recommended if:


the curve has progressed despite bracing



the curve is greater than 40–50 degrees before
growth has stopped in an adolescent



the curve is greater than 50 degrees and continues to
increase in an adult



there is significant pain

Orthopedic surgery for neuromuscular scoliosis is
often done earlier. The goals of surgery are to correct
the deformity as much as possible, to prevent further
deformity, and to eliminate pain as much as possible.
Surgery can usually correct 40–50% of the curve, and
sometimes as much as 80%. Surgery cannot always
completely remove pain.

This woman suffers from scoliosis, or curvature of the spine.
(Custom Medical Stock Photo. Reproduced by permission.)

For children or adolescents whose curves progress
to 30 degrees, and who have a year or more of growth
left, bracing may be required. Bracing cannot correct
curvature, but may be effective in halting or slowing
progression. Bracing is rarely used in adults, except
where pain is significant and surgery is not an option,
as in some elderly patients.
Two general styles of braces are used for daytime
wear. The Milwaukee brace consists of metal uprights
attached to pads at the hips, rib cage, and neck. The
underarm brace uses rigid plastic to encircle the lower
rib cage, abdomen, and hips. Both these brace types
hold the spine in a vertical position. Because it can be
worn out of sight beneath clothing, the underarm
brace is better tolerated and often leads to better
compliance. A third style, the Charleston bending
brace, is used at night to bend the spine in the opposite
direction. Braces are often prescribed to be worn for
22–23 hours per day, though some clinicians allow or
encourage removal of the brace for exercise.
GALE ENCYCLOPEDIA OF MEDICINE

The surgical procedure for scoliosis is called spinal
fusion, because the goal is to straighten the spine as
much as possible, and then to fuse the vertebrae together
to prevent further curvature. To achieve fusion, the
involved vertebra are first exposed, and then scraped
to promote regrowth. Bone chips are usually used to
splint together the vertebrae to increase the likelihood of
fusion. To maintain the proper spinal posture before
fusion occurs, metal rods are inserted alongside the
spine, and are attached to the vertebrae by hooks,
screws, or wires. Fusion of the spine makes it rigid and
resistant to further curvature. The metal rods are no
longer needed once fusion is complete, but are rarely
removed unless their presence leads to complications.
Spinal fusion leaves the involved portion of the
spine permanently stiff and inflexible. While this leads
to some loss of normal motion, most functional activities are not strongly affected, unless the very lowest
portion of the spine (the lumbar region) is fused.
Normal mobility, exercise, and even contact sports
are usually all possible after spinal fusion. Full recovery takes approximately six months.

Alternative treatment
Numerous alternative therapies have been touted
to provide relief and help for individuals with scoliosis,
but none have been proven beneficial in clinical
trials. These include massage, physical therapy, and
electrical stimulation. In addition, alternatives such as
3315

Scoliosis

Bracing may be appropriate for scoliosis due to
some types of neuromuscular disease, including spinal
muscular atrophy, before growth is finished. Duchenne
muscular dystrophy is not treated by bracing, since
surgery is likely to be required, and since later surgery
is complicated by loss of respiratory capacity.

Scrotal nuclear medicine scan

Prevention

KEY TERMS
Cobb angle —A measure of the curvature of scoliosis, determined by measurements made on x rays.
Rolfing —A system of soft tissue manipulation and
movement education to realign and reorient the
body.
Scoliometer —A tool for measuring trunk asymmetry; it includes a bubble level and angle measure.
Spondylosis —Arthritis of the spine.

There is no known way to prevent the development of scoliosis. Progression of scoliosis may be prevented through bracing or surgery.
Exercise and physical fitness are of paramount
importance for all individuals affected with scoliosis.
They not only work to maintain flexibility and health,
but decrease the likelihood of osteoporosis, which in
these individuals, can be extremely debilitating.
Resources
BOOKS

physical therapy, rolfing, or chiropractice manipulation may provide improved flexibility, stronger muscles, and pain relief, but cannot prevent or correct the
curvature of the spine or its natural progression.
Although important for general health and
strength, exercise has not been shown to prevent or
slow the development of scoliosis. It may help relieve
pain from scoliosis by helping to maintain range of
motion. Aquatic exercise, in particular, can increase
flexibility and improve posture, balance, coordination,
and range of motion. Because it decreases joint compression, it can lessen the pain caused by scoliosis or surgery.
Good nutrition is also important for general health,
but no specific dietary regimen has been shown to
control scoliosis development. In particular, dietary
calcium levels do not influence scoliosis progression.

Lyons, Brooke, et al. Scoliosis: Ascending the Curve. New
York: M. Evans & Co., 1999.
PERIODICALS

Bridwell, KH, et al., editors. ‘‘Parents’ and Patients’
Preferences and Concerns in Idiopathic Adolescent
Scoliosis: A Cross-Sectional Preoperative Analysis.’’
Spine 25, no. 18 (September 2000): 2392-9.
ORGANIZATIONS

American Physical Therapy Assocation. Scoliosis, P.O. Box
37257, Washington, DC 20013.
Center for Spinal Disorders, PC. 8515 Pearl Street, Suite
350, Thornton, CO 80229. (303) 287-2800; fax: (303)
287-7357. <http://www.cntrforspinaldisorders.com>.
National Scoliosis Foundation. 72 Mount Auburn St.,
Watertown, MA 02172. (617) 926-0397.
The Scoliosis Association. PO Box 811705, Boca Raton, FL
33481-0669. (407) 368-8518.
OTHER

‘‘Chiropractic Treatment of Scoliosis.’’ Scoliosis World.

Chiropractic treatment may relieve pain, but it
cannot halt scoliosis development, and should not be
a substitute for conventional treatment of progressing
scoliosis. Acupuncture and acupressure may also help
reduce pain and discomfort, but they cannot halt scoliosis development either.

Prognosis
The prognosis for a person with scoliosis depends
on many factors, including the age at which scoliosis
begins and the treatment received. More importantly,
mostly unknown individual factors affect the likelihood of progression and the severity of the curve.
Most cases of mild adolescent idiopathic scoliosis
need no treatment and do not progress. Untreated
severe scoliosis often leads to spondylosis, and may
impair breathing. Degenerative arthritis of the spine,
sciatica, and severe physical deformities can also result
if severe scoliosis is left untreated. Finally, scoliosis
can also poorly affect the individual’s self-esteem and
cause serious emotional problems.
3316

Liz Meszaros

Scrotal nuclear medicine scan
Definition
Scrotal nuclear medicine scan is a study of the
blood circulation in the scrotum using radioactive
contrast agent to highlight obstruction.

Purpose
This test is used almost exclusively to differentiate
infection in the testis (testicle) from twisting and
infarction. Infection is called epididymitis because it
mostly involves a collection of tubules on top of the
testicle called the epididymis. Twisting of the testis
shuts off its blood supply and is called testicular
GALE ENCYCLOPEDIA OF MEDICINE

Radioisotope—An unstable form of an element that
gives off radiation to become stable.
Scrotum—The bag of skin below the penis that
contains the testes.

torsion. Both conditions cause a very painful, swollen
testis on one side. Both occur most often in young
men, although infection usually occurs at a slightly
greater age. The infection increases the blood supply,
and the torsion cuts off the blood supply. This is an
ideal situation for a blood flow study.
The distinction is critically important, because testicular torsion must be untwisted immediately or the
testis will die. On the other hand, epididymitis responds
to antibiotics, and surgery might further injure it.

Description
A radioisotope, technetium-99, combined in a
chemical (pertechnate) is injected intravenously while
the patient is under a special machine that detects
radiation. This radiation detector, called a gamma
camera, scans the scrotum at one minute intervals for
about five minutes, then less often for another 10 or 15
minutes. It then creates pictures (either x ray or polaroid) that reveal where the isotope went in the scrotum.
Since both sides are scanned, even greater accuracy is
obtained by comparison.

Preparation
This procedure is usually done as an emergency to
determine the need for immediate surgery.

Risks
The amount of radiation is so slight that even the
sensitive testicular tissue is at minimum risk.

Normal results
Blood flow appears unobstructed.

Abnormal results

Blood flow illuminated in a ‘‘donut’’ shaped pattern
that indicates torsion that has resolved itself within
the last few days.

Resources
BOOKS

Rajfer, Jacob. ‘‘Congenital Anomalies of the Testes and
Scrotum.’’ In Campbell’s Urology, edited by Patrick C.
Walsh, et al. Philadelphia: W. B. SaundersCo., 1998.

J. Ricker Polsdorfer, MD

Scrotal sonogram see Scrotal ultrasound

Scrotal ultrasound
Definition
Scrotal ultrasound is an imaging technique used
for the diagnosis of suspected abnormalities of the
scrotum. It uses harmless, high-frequency sound
waves to form an image. The sound waves are reflected
by scrotal tissue to form a picture of internal structures. It is not invasive and involves no radiation.

Purpose
Ultrasound of the scrotum is the primary imaging
method used to evaluate disorders of the testicles and
surrounding tissues. It is used when a patient has acute
pain in the scrotum. Some of the problems for which
the use of scrotal ultrasound is valuable include an
absent or undescended testicle, an inflammation problem, testicular torsion, a fluid collection, abnormal
blood vessels, or a mass (lump or tumor).
A sudden onset of pain in the scrotum is considered a serious problem, as delay in diagnosis and
treatment can lead to loss of function. Epididymitis is
the most common cause of this type of pain.
Epididymitis is an inflammation of the epididymis, a
tubular structure that transports sperm from the
testes. It is most often caused by bacterial infection,
but may occur after injury, or arise from an unknown
cause. Epididymitis is treatable with antibiotics, which
usually resolves pain quickly. Left untreated, this condition can lead to abscess formation or loss of blood
supply to the testicle.



Increased blood flow indicating infection



No blood flow indicating testicular torsion

Testicular torsion is the twisting of the spermatic
cord that contains the blood vessels which supply the
testicles. It is caused by abnormally loose attachments
of tissues that are formed during fetal development.

GALE ENCYCLOPEDIA OF MEDICINE

3317

Three possible possible images appear. They are:

Scrotal ultrasound



KEY TERMS

Scrub typhus

Torsion can be complete, incomplete, or intermittent.
Spontaneous detorsion, or untwisting, can occur,
making diagnosis difficult. Testicular torsion arises
most commonly during adolescence, and is acutely
painful. Scrotal ultrasound is used to distinguish this
condition from inflammatory problems, such as epididymitis. Testicular torsion is a surgical emergency; it
should be operated on as soon as possible to avoid
permanent damage to the testes.
A scrotal sac with an absent testicle may be the
result of a congenital anomaly (an abnormality present at birth), where a testicle fails to develop. More
often, it is due to an undescended testicle. In the fetus,
the testicles normally develop just outside the abdomen and descend into the scrotum during the seventh
month. Approximately 3% of full-term baby boys
have undescended testicles. It is important to distinguish between an undescended testicle and an absent
testicle, as an undescended testicle has a very high
probability of developing cancer.
Ultrasound can be used to locate and evaluate
masses in the scrotum. Most masses within the testicle
are malignant or cancerous, and most outside the
testicle are benign. Primary cancer of the testicles is
the most common malignancy in men between the ages
of 15-35. Fluid collections and abnormalities of the
blood vessels in the scrotum may appear to the physician as masses and need evaluation by ultrasound. A
hydrocele, the most common cause of painless scrotal
swelling, is a collection of fluid between two layers of
tissue surrounding the testicle. An abnormal enlargement of the veins which drain the testicles is called a
varicocele. It can cause discomfort and swelling, which
can be examined by touch (palpated). Varicocele is a
common cause of male infertility.

KEY TERMS
Hydrocele— A collection of fluid between two
layers of tissue surrounding the testicle; the most
common cause of painless scrotal swelling.
Varicocele— An abnormal enlargement of the
veins which drain the testicles.

appear on a monitor screen. There is no discomfort
from the study itself. However, if the scrotum is very
tender, even the slight pressure involved may be
painful.

Normal results
A normal study would reveal testicles of normal
size and shape, with no masses.

Abnormal results
An abnormal result of an ultrasound of the scrotum may reveal an absent or undescended testicle, an
inflammation problem, testicular torsion, a fluid collection, abnormal blood vessels, or a mass.
Resources
BOOKS

Leonhardt, Wayne C. ‘‘Scrotum.’’ In Abdomen and
Superficial Structures, edited by Diane M. Kawamura,
2nd ed. Philadelphia: Lippincott, 1997.

Ellen S. Weber, MSN

Precautions
Clear scrotal ultrasound images are difficult to
obtain if a patient is unable to remain still.

Description
The patient lies on his back on an examining table.
The technologist will usually take a history of the
problem, then gently palpate the scrotum. A rolled
towel is placed between the patient’s legs to support
the scrotum. The penis is lifted up onto the abdomen
and covered. A gel that enhances sound transmission
is put directly on the scrotum. The technologist then
gently places a transducer (an electronic imaging
device) against the skin. It is moved over the area
creating images from reflected sound waves, which
3318

Scrub typhus
Definition
Scrub typhus is an infectious disease that is transmitted to humans from field mice and rats through the
bite of mites that live on the animals. The main symptoms of the disease are fever, a wound at the site of the
bite, a spotted rash on the trunk, and swelling of the
lymph glands.

Description
Scrub typhus is caused by Rickettsia tsutsugamushi, a tiny parasite about the size of bacteria that
GALE ENCYCLOPEDIA OF MEDICINE

headache, infection of the mucous membrane lining
the eyes (the conjunctiva), and swelling of the lymph
nodes (lymphadenopathy). A wound (lesion) is often
seen at the site of the chigger bite. Bite wounds are
common in whites but rare in Asians.

R. tsutsugamushi lives primarily in mites that
belong to the species Leptotrombidium (Trombicula)
akamushi and Leptotrombidium deliense. In Japan,
some cases of scrub typhus have been reportedly transmitted by mites of the species Leptotrombidium scutellare and Leptotrombidium pallidum. The mites have
four-stage life cycles: egg, larva, nymph, and adult.
The larva is the only stage that can transmit the disease
to humans and other vertebrates.

The initial lesion, which is about 1 cm (0.4 in) in
diameter and flat, eventually becomes elevated and
filled with fluid. After it ruptures, it becomes covered
with a black scab (eschar). The patient’s fever rises
during the first week, generally reaching 40–40.58C
(104–1058F). About the fifth day of fever, a red
spotted rash develops on the trunk, often extending
to the arms and legs. It may either fade away in a few
days or may become spotted and elevated (maculopapular) and brightly colored. Cough is present during
the first week of the fever. An infection of the lung
(pneumonitis) may develop during the second week.

The tiny chiggers (mite larvae) attach themselves
to the skin. During the process of obtaining a meal,
they may either acquire the infection from the host or
transmit the rickettsiae to other mammals or humans.
In regions where scrub typhus is a constant threat, a
natural cycle of R. tsutsugamushi transmission occurs
between mite larvae and small mammals (e.g., field
mice and rats). Humans enter a cycle of rickettsial
infection only accidentally.
Scrub typhus is also known as tsutsugamushi disease. The name tsutsugamushi is derived from two
Japanese words: tsutsuga, meaning something small
and dangerous, and mushi, meaning creature. The
infection is called scrub typhus because it generally
occurs after exposure to areas with secondary (scrub)
vegetation. It has recently been found, however, that
the disease can also be prevalent in such areas as sandy
beaches, mountain deserts, and equatorial rain forests.
Therefore, it has been suggested that the names miteborne typhus, or chigger-borne typhus, are more
appropriate. Since the disease is limited to eastern
and southeastern Asia, India, northern Australia and
the adjacent islands, it is also commonly referred to as
tropical typhus.
The seasonal occurrence of scrub typhus varies
with the climate in different countries. It occurs more
frequently during the rainy season. Certain areas such
as forest clearings, riverbanks, and grassy regions provide optimal conditions for the infected mites to
thrive. These small geographic regions are high-risk
areas for humans and have been called scrub-typhus
islands.

Causes and symptoms
The incubation period of scrub typhus is about 10
to 12 days after the initial bite. The illness begins
rather suddenly with shaking chills, fever, severe
GALE ENCYCLOPEDIA OF MEDICINE

In severe cases, the patient’s pulse rate increases
and blood pressure drops. The patient may become
delirious and lose consciousness. Muscular twitching
may develop. Enlargement of the spleen is observed.
Inflammation of the heart muscle (interstitial myocarditis) is more common in scrub typhus than in other
rickettsial diseases. In untreated patients, high fever
may last for more than two weeks. With specific therapy, however, the fever breaks within 36 hours. The
patient’s recovery is prompt and uneventful.

Diagnosis
Patient history and physical examination
Differentiating scrub typhus from other forms of
typhus as well as from fever, typhoid and meningococcal infections is often difficult during the first several days before the initial rash appears. The
geographical location of scrub typhus, the initial sore
caused by the chigger bite, and the occurrence of specific proteins capable of destroying the organism (antibodies) in the blood, provide helpful clues and are
useful in establishing the diagnosis.
Laboratory tests
Diagnostic procedures involving the actual isolation of rickettsiae from the blood or other body tissues
are usually expensive, time-consuming, and hazardous
to laboratory workers. As a result, several types of
tests known as serological (immunological) tests are
used widely to confirm the clinical diagnosis in the
laboratory.
Specific antibodies develop in the body in
response to an infection. The development of antibodies during the recovery period indicates that an
3319

Scrub typhus

belongs to the family Rickettsiaceae. Under the microscope, rickettsiae are either rod-like (bacilli) or spherical (cocci) in shape. Because they are intracellular
parasites, they can live only within the cells of other
animals.

Scrub typhus

immune response is present. The formation of antibodies is the basic principle of a serological test. Three
different tests are available to diagnose rickettsial
infections. The most widely used is the Weil-Felix
test. This test is based on the fact that some of the
antibodies that are formed in the body during a rickettsial infection can react with certain strains (OX-2
and OX-19) of Proteus bacteria and cause them to
clump (agglutinate). The clumping is easily seen
under the microscope. The Weil-Felix test is easy and
inexpensive to perform, with the result that it is widely
used. The Weil- Felix test, however, is not very specific. In addition, the clumping is not detectable until
the second week of the illness, which limits the test’s
usefulness in early diagnosis.
A second test known as a complement fixation
(CF) test is based on the principle that if antibodies
are formed in the body in response to the illness, then
the antigen and the antibody will form complexes.
These antigen-antibody complexes have the ability to
inactivate, or fix, a protein that is found in blood
serum (serum complement). The serum complement
fixation can be measured using standardized biochemical tests and confirms the presence of antibodies. A
third test known as the fluorescent antibody test uses
fluorescent tags that are attached to antibodies for
easy detection. This test has been developed using
three strains of Rickettsia tsutsugamushi and has proven to be the most specific for diagnosis.

Treatment
Scrub typhus is treated with antibiotics.
Chloramphenicol (Chloromycetin, Fenicol) and tetracycline (Achromycin, Tetracyn) are the drugs of
choice. They bring about prompt disappearance of
the fever and dramatic clinical improvement. If the
antibiotic treatment is discontinued too quickly, especially in patients treated within the first few days of the
fever, relapses may occur. In patients treated in the
second week of illness, the antibiotics may be stopped
one to two days after the fever disappears.
Antibiotics are given intravenously to patients too
sick to take them by mouth. Patients who are severely
ill and whose treatment was delayed may be given
corticosteroids in combination with antibiotics for
three days.

Prognosis
Before the use of antibiotics, the mortality rate for
scrub typhus varied from 1–60%, depending on the
geographic area and the rickettsial strain. Recovery
3320

KEY TERMS
Agglutinin—An antibody that causes particulate
antigens such as bacteria or other cells to clump
together.
Endemic area—A geographical region where a particular disease is prevalent.
Eschar—A hard crust or scab. In scrub typhus, an
eschar forms over the initial sore from the chigger
bite.
Intracellular parasite—An organism which can
only feed and live within the cell of a different
animal.
Maculopapular rash—A rash characterized by
raised, spotted lesions.
Prophylactic dosage—Giving medications to prevent or protect against diseases.
Rickettsia—A rod-shaped infectious microorganism that can reproduce only inside a living cell.
Scrub typhus is a rickettsial disease.
Serological tests—Tests of immune function that
are performed using the clear yellow liquid part of
blood.

also took a long time. With modern treatment methods, however, deaths are rare and the recovery period
is short.

Prevention
General precautions
As of early 2004 there are no effective vaccines for
scrub typhus. In endemic areas, precautions include
wearing protective clothing. Insect repellents containing dibutyl phthalate, benzyl benzoate, diethyl toluamide, and other substances can be applied to the skin
and clothing to prevent chigger bites. Clearing of
vegetation and chemical treatment of the soil may
help to break up the cycle of transmission from
chiggers to humans to other chiggers.
Prophylactic antibiotic dosage
It has been shown that a single oral dose of chloramphenicol or tetracycline given every 5 days for a
total of 35 days, with 5-day nontreatment intervals,
actually produces active immunity to scrub typhus.
This procedure is recommended under special circumstances in certain areas where the disease is endemic.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Scrub Typhus.’’ Section 13, Chapter 159 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PERIODICALS

Cheng, V. C., A. K. Wu, I. F. Hung, et al. ‘‘Clinical
Deterioration in Community Acquired Infections
Associated with Lymphocyte Upsurge in
Immunocompetent Hosts.’’ Scandinavian Journal of
Infectious Diseases 36, no. 10 (2004): 743–751.
Ralph, A., M. Raines, P. Whelan, and B. J. Currie. ‘‘Scrub
Typhus in the Northern Territory: Exceeding the
Boundaries of Litchfield National Park.’’
Communicable Diseases Intelligence 28 (February
2004): 267–269.
Takahashi, M., H. Misumi, H. Urakami, et al. ‘‘Mite
Vectors (Acari: Trombiculidae) of Scrub Typhus in a
New Endemic Area in Northern Kyoto, Japan.’’
Journal of Medical Entomology 41 (January 2004):
107–114.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Lata Cherath, PhD
Rebecca J. Frey, PhD

Scurvy
Definition
Scurvy is a condition caused by a lack of vitamin
C (ascorbic acid) in the diet. Signs of scurvy include
tiredness, muscle weakness, joint and muscle aches,
a rash on the legs, and bleeding gums. In the past,
scurvy was common among sailors and other people
deprived of fresh fruits and vegetables for long periods
of time.

Description
Scurvy is very rare in countries where fresh fruits
and vegetables are readily available and where processed foods have vitamin C added. Vitamin C is an
important antioxidant vitamin involved in the development of connective tissues, lipid and vitamin metabolism, biosynthesis of neurotransmitters, immune
function, and wound healing. It is found in fruits,
GALE ENCYCLOPEDIA OF MEDICINE

especially citrus fruits like oranges, lemons, and grapefruit, and in green leafy vegetables like broccoli
and spinach. In adults, it may take several months of
vitamin C deficiency before symptoms of scurvy
develop.
Currently, the recommended dietary allowance
(RDA) for vitamin C is 50–60 mg/day for adults; 35
mg/day for infants; 40–45 mg/day for children 1–14;
70 mg/day during pregnancy; and 90–95 mg/day during lactation. The body’s need for vitamin C increases
when a person is under stress, smoking, or taking
certain medications.

Causes and symptoms
A lack of vitamin C in the diet is the primary cause
of scurvy. This can occur in people on very restricted
diets, who are under extreme physiological stress (for
example, during an infection or after an injury), and in
chronic alcoholics. Infants can develop scurvy if they
are weaned from breast milk and switched to cow’s
milk without an additional supplement of vitamin C.
Babies of mothers who took extremely high doses of
vitamin C during pregnancy can develop infantile
scurvy. In children, the deficiency can cause painful
swelling of the legs along with fever, diarrhea, and
vomiting. In adults, early signs of scurvy include feeling weak, tired, and achy. The appearance of tiny red
blood-blisters to larger purplish blotches on the skin of
the legs is a common symptom. Wound healing may
be delayed and scars that had healed may start to
break down. The gums swell and bleed easily, eventually leading to loosened teeth. Muscle and joint pain
may also occur.

Diagnosis
Scurvy is often diagnosed based on the symptoms
present. A dietary history showing little or no fresh
fruits or vegetables are eaten may help to diagnose
vitamin C deficiency. A blood test can also be used
to check the level of ascorbic acid in the body.

Treatment
Adult treatment is usually 300–1,000 mg of ascorbic acid per day. Infants should be treated with 50 mg
of ascorbic acid up to four times per day.

Prognosis
Treatment with vitamin C is usually successful, if
the deficiency is recognized early enough. Left
untreated, the condition can cause death.
3321

Scurvy

Resources

Seasonal affective disorder

Seasonal affective disorder
Definition
Seasonal affective disorder (SAD) is a form of
depression most often associated with the lack of daylight in extreme northern and southern latitudes from
the late fall to the early spring.

Description
Although researchers are not certain what causes
seasonal affective disorder, they suspect that it has
something to do with the hormone melatonin.
Melatonin is thought to play an active role in regulating the ‘‘internal body clock,’’ which dictates when
humans feel like going to bed at night and getting up
in the morning. Although seasonal affective disorder is
most common when light is low, it may occur in the
spring, and it is then often called reverse SAD.
An x-ray image of an infant suffering from scurvy. (Photograph
by Lester V. Bergman, Corbis Images. Reproduced by permission.)

KEY TERMS
Ascorbic acid—Another term for vitamin C, a nutrient found in fresh fruits and vegetables. Good sources
of vitamin C in the diet are citrus fruits like oranges,
lemons, limes, and grapefruits, berries, tomatoes,
green peppers, cabbage, broccoli, and spinach.
Recommended dietary allowance (RDA)—The
daily amount of a vitamin the average person
needs to maintain good health.

Prevention
Eating foods rich in vitamin C every day prevents
scurvy. A supplement containing the RDA of vitamin
C will also prevent a deficiency. Infants who are being
weaned from breast milk to cow’s milk need a supplement containing vitamin C.
Resources
BOOKS

Stein, Jay H., editor. ‘‘Ascorbic Acid (Vitamin C) Deficiency.’’
In Internal Medicine. St. Louis: Mosby, 1998.

Altha Roberts Edgren

Seafood poisoning see Fish and shellfish
poisoning
3322

Causes and symptoms
The body produces more melatonin at night than
during the day, and scientists believe it helps people feel
sleepy at nighttime. There is also more melatonin in the
body during winter, when the days are shorter. Some
researchers believe that excessive melatonin release during winter in people with SAD may account for their
feelings of drowsiness or depression. One variation on
this idea is that, during winter, people’s internal clocks
may become out of sync with the light-dark cycle, leading to a long-term disruption in melatonin release.
Seasonal affective disorder, while not an official
category of mental illness listed by the American
Psychiatric Association, is estimated to affect 10 million
Americans, most of whom are women. Another 25
million Americans may have a mild form of SAD,
sometimes called the ‘‘winter blues’’ or ‘‘winter
blahs.’’ The risk of SAD increases the further from
the equator a person lives.
The symptoms of SAD are similar to those of
other forms of depression. People with SAD may feel
sad, irritable, or tired, and may find themselves sleeping too much. They may also lose interest in normal or
pleasurable activities (including sex), become withdrawn, crave carbohydrates, and gain weight.

Diagnosis
Doctors usually diagnose seasonal affective disorder based on the patient’s description of symptoms,
including the time of year they occur.
GALE ENCYCLOPEDIA OF MEDICINE

The first-line treatment for seasonal affective
disorder is light therapy, exposing the patient to bright
artificial light to compensate for the gloominess of
winter. Light therapy uses a device called a light box,
which contains a set of fluorescent or incandescent
lights in front of a reflector. Typically, the patient
sits for 30 minutes next to a 10,000-lux box (which is
about 50 times as bright as ordinary indoor light).
Light therapy appears to be safe for most people.
However, it may be harmful for those with eye
diseases. The most common side effects are vision
problems such as eye strain, headaches, irritability,
and insomnia. In addition, hypomania (elevated or
expansive mood, characterized by hyperactivity and
inflated self esteem) may occasionally occur.
Recently, researchers have begun testing whether
people who do not completely respond to light therapy
can benefit from tiny doses of the hormone melatonin
to reset the body’s internal clock. Early results look
promising, but the potential benefits must be confirmed in larger studies before this type of treatment
becomes widely accepted.
Like other types of mood disorders, seasonal affective disorder may also respond to medication and
psychotherapy. The four different classes of drugs
used for mood disorders are:


heterocyclic antidepressants (HCAs), such as amitriptyline (Elavil)



selective serotonin reuptake inhibitors (SSRIs),
such as fluoxetine (Prozac), paroxetine (Paxil), and
sertraline (Zoloft)



monoamine oxidase inhibitors (MAO inhibitors),
such as phenelzine sulfate (Nardil) and tranylcypromine sulfate (Parnate)



Lithium salts, such as lithium carbonate (Eskalith),
often used in people with bipolar mood disorders, are
often useful with SAD patients; many SAD patients
also suffer from bipolar disorder (excessive mood
swings; formerly known as manic depression)

A number of psychotherapy approaches are useful as well. Interpersonal psychotherapy helps patients
recognize how their mood disorder and their interpersonal relationships interact. Cognitive-behavioral
therapy explores how the patient’s view of the world
may be affecting mood and outlook.

Prognosis
Most patients with seasonal affective disorder
respond to light therapy and/or antidepressant drugs.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cognitive behavioral therapy—Psychotherapy
aimed at helping people change their attitudes,
perceptions, and patterns of thinking.
Melatonin—A naturally occurring hormone
involved in regulating the body’s ‘‘internal clock.’’
Serotonin—A chemical messenger in the brain
thought to play a role in regulating mood.

Resources
ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW,
Washington DC 20005. (888) 357-7924. <http://
www.psych.org>.
National Depressive and Manic Depressive Association
(NDMDA). 730 N. Franklin St., Ste. 501, Chicago, IL
60610. (800) 826-3632. <http://www.ndmda.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,
MD 20857. (888) 826-9438. <http://
www.nimh.nih.gov>.

Robert Scott Dinsmoor

Seasonal depression see Seasonal affective
disorder
Seatworm infection see Enterobiasis

Seborrheic dermatitis
Definition
Seborrheic dermatitis is a common inflammatory
disease of the skin characterized by scaly lesions
usually on the scalp, hairline, and face.

Description
Seborrheic dermatitis appears as red, inflamed
skin covered by greasy or dry scales that may be
white, yellowish, or gray. It can effect the scalp, eyebrows, forehead, face, folds around the nose and ears,
the chest, armpits (axilla), and groin. Dandruff and
cradle cap are mild forms of seborrheic dermatitis, and
appear as fine white scales without inflammation.
3323

Seborrheic dermatitis

Treatment

Seborrheic dermatitis

KEY TERMS
Acne—A chronic inflammation of the sebaceous
glands that manifests as blackheads, whiteheads,
and/or pustules on the face or trunk.
Psoriasis— A skin disorder of chronic, itchy scaling
most commonly at sites of repeated minor trauma
(e.g. elbows, knees, and skin folds). It affects up to
2% of the population in Western countries—males
and females equally.
Rosacea—A chronic inflammation of the face, with
associated scattered round nodules and increased
reactivity of the facial capillaries to heat. It is most
common in females, aged 30–50 years.

intensity over time. When scaling is present, it may be
accompanied by itching that can lead to secondary
infection.

Diagnosis
This young boy is afflicted with seborrheic dermatitis.
(Custom Medical Stock Photo. Reproduced by permission.)

Causes and symptoms
The cause of seborrheic dermatitis is unclear,
though it is has been linked to genetic or environmental factors. Pityrosporum ovale, a species of yeast normally found in hair follicles, has been proposed as one
possible causative factor. A high fat diet and alcohol
ingestion are thought to play some role. Other possible
risk factors include:


stress and fatigue



weather extremes (e. g. hot, humid weather or cold,
dry weather)



oily skin



infrequent shampoos



obesity



Parkinson’s disease



AIDS



use of drying lotions that contain alcohol



other skin disorders (for example acne, rosacea, or
psoriasis)

Mild forms of the disorder may be asymptomatic.
Symptoms also disappear and reappear, and vary in
3324

The diagnosis of seborrheic dermatitis is based on
assessment of symptoms, accompanied by consideration of medical history.

Treatment
Treatment consists of vigorous shampoos with
preparations that assist with softening and removing
the scaly accumulations. For mild cases, a nonprescription shampoo with selenium sulfide or zinc
pyrithione may be used. For more severe problems,
the doctor may prescribe shampoos containing coal
tar or scalp creams containing cortisone. The antiseborrheic shampoo should be left on the scalp for approximately five minutes before rinsing out. Hydrocortisone
cream may also be ordered for application to the
affected areas on the face and body. Application of
the hydrocortisone should be discontinued when the
condition clears and restarted with recurrence.

Prognosis
This chronic condition may be characterized by
long periods of inactivity. Symptoms in the acute
phase can be controlled with appropriate treatment.

Prevention
The condition cannot be prevented. The severity
and frequency of flare-ups may be minimized with
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Smoking, which impairs red blood cells’ ability to
deliver oxygen to body tissues, can cause secondary
polycythemia. So can the following conditions:

Resources



carbon monoxide poisoning

BOOKS



chronic heart or lung disease



hormonal (endocrine) disorders



exposure to high altitudes



kidney cysts



tumors of the brain, liver, or uterus.

Monahan, Frances, and Marianne Neighbors. Medical
Surgical Nursing: Foundations for Clinical Practice.
Philadelphia: W. B. Saunders,1998.

Kathleen D. Wright, RN

Causes of spurious polycythemia include:

Secobarbital see Barbiturates
Secondary erythrocytosis see Secondary
polycythemia

Secondary polycythemia
Definition
Secondary polycythemia is an acquired form of a
rare disorder characterized by an abnormal increase in
the number of mature red cells in the blood.
Secondary polycythemia is also called secondary
erythrocytosis.

Description
Polycythemia means too many red blood cells.
The resulting excess of red cells thickens the blood
and impedes its passage through small blood vessels.
Secondary polycythemia usually affects people
between the ages of 40 and 60.
Types of secondary polycythemia
Known as spurious polycythemia, stress polycythemia, or Gaisbock’s syndrome, relative polycythemia is characterized by normal numbers of red blood
cells but decreased levels of plasma (the fluid part of
the blood). Overweight, middle-aged white men who
smoke, have high blood pressure, and are on diuretic
medicines to remove excess water from their bodies
may develop Gaisbock’s syndrome.
In smoker’s polycythemia, the number of red
blood cells is elevated. Plasma levels are abnormally
low.
GALE ENCYCLOPEDIA OF MEDICINE



burns



diarrhea



hemoconcentration (higher-than-normal concentration of cells and solids in the blood, usually due to
becoming dehydrated or taking diuretics)



stress

Weakness, headaches, and fatigue are usually the
first symptoms of secondary polycythemia. Patients
may feel lightheaded or experience shortness of breath.
Visual disturbances associated with this disorder
include distorted vision, blind spots, and flashes of
light. The gums and small cuts are likely to bleed,
and the hands and feet may burn. Extensive itching
often occurs after taking a bath or shower.
Pain in the chest or leg muscles is common. The
face often becomes ruddy, then turns blue after exercise or other exertion. Confusion and ringing in the
ears (tinnitus) may also occur.

Diagnosis
A very important part of diagnosing secondary
polycythemia is differentiating it from primary polycythemia (also called polycythemia rubra vera or
Vaquez’ disease). Unlike secondary polycythemia, primary polycythemia cannot be traced to an underlying
condition such as smoking, high altitude, or chronic
lung disease.
Doctors diagnose polycythemia by measuring
oxygen levels in blood drawn from an artery. A patient
whose oxygen level is abnormally low probably has
secondary polycythemia. Erythropoietin may also be
measured. Levels of this hormone, which stimulates
the bone marrow to produce red blood cells, may be
normal or elevated in a patient with secondary polycythemia. Red blood cell mass is also frequently measured in diagnosing the disorder.
3325

Secondary polycythemia

frequent shampoos, thorough drying of skin folds
after bathing, and wearing of loose, ventilating clothing. Foods that appear to worsen the condition should
be avoided.

Sedation

Imaging studies are sometimes performed to
determine whether the spleen and liver are enlarged
and to detect erythropoietin-producing kidney lesions.
Other diagnostic procedures include chest x rays and
an electrocardiogram (EKG).

Treatment
Secondary polycythemia is treated primarily by
treating the underlying condition causing the disorder.
For example, patients with Gaisbock’s syndrome are
often taken off diuretics and encouraged to lose
weight. Lung disorders, such as chronic obstructive
pulmonary disease (COPD), may cause secondary
polycythemia; treating the lung disorder generally
improves the polycythemia.
Some medications may also be taken to treat
symptoms caused by polycythemia. For example, antihistamines can alleviate itching, and aspirin can soothe
burning sensations and bone pain.
Until the underlying condition is controlled, doctors use bloodletting (phlebotomy) to reduce the number of red blood cells in the patient’s body. In most
instances, a pint of blood is drained from the patient as
needed and tolerated, until the hematocrit (the proportion of red cells in the blood) reaches an acceptable
level. Chemotherapy is not used to treat secondary
polycythemia; however, it may be used to treat the
primary form.

Prognosis
Curing or removing the underlying cause of this
disorder generally eliminates the symptoms.
Resources
OTHER

‘‘Secondary Erythrocytosis.’’ The Merck Page. June 3, 1998.
<http://www.merck.com>.

Maureen Haggerty

SED rate see Erythrocyte sedimentation rate

Sedation
Definition
Sedation is the act of calming by administration of
a sedative. A sedative is a medication that commonly
induces the nervous system to calm.
3326

Purpose
The process of sedation has two primary intentions. First, sedation is recommended to allow patients
the ability to tolerate unpleasant diagnostic or surgical
procedures and to relieve anxiety and discomfort.
Second, sedation for uncooperative patients may
expedite and simplify special procedures that require
little or no movement. Additionally, sedation is often
desirable to diminish fear associated with operative
procedures. Sedation is typically used for common
diagnostic tests that require prolonged immobilization
such as magnetic resonance imaging (MRI) and computed axial tomography (CAT) scanning. Some cases
that require sedation may also necessitate the use of
analgesics to decrease pain associated with a procedure
or test.

Precautions
Benzodiazepines (common sedative medication)
have a cumulative effect. This means that if the patient
has not had time to metabolize the previous dose and
ingests more, then the sedative effect may increase.
Because of these additive effects, these medications
taken with other sedatives or alcohol (also a sedative
hypnotic drug) may increase chances for accidental
death. In general, most of the medications that induce
sedation may alter breathing and cardiac stability. In
patients with preexisting lung and/or heart disease,
these medications should be monitored closely or not
prescribed.

Description
The future of anesthetic care involves the simultaneous administration of several drugs including IV
medications and inhaled anesthetics. An extensive
survey of death in 100,000 cases published in 1988
revealed that death within seven days was 2.9 times
greater when one or two anesthetic drugs were used
than when using three or more medications. As of
2000 this study is accepted as standard practice and
multiple IV anesthetics is the preferable recommendation for optimal patient care.
The procedure for sedation is usually explained
to the patient by an attending clinician. An IV access
line is set in place for fluid replacement and injection
of medications. A history is usually taken to assess
risk and choice of medication. The patient typically
signs consent forms and the possible side effects
are explained. The day before the test, the patient
may be required to maintain specified dietary
restriction.
GALE ENCYCLOPEDIA OF MEDICINE

Preparation
Usually procedures for conscious sedation do not
require preoperative or pre-testing orders. Clinical
situations for unconscious sedation typically involve
eating and drinking protocols starting the day before
the procedure.
The age and physical status of the patient is useful
in determining sensitivity. A detailed past history,
especially prior experiences with sedatives and other
anesthetics is an important part of preparatory assessment. It is important to determine if there were any
untoward side effects associated with a previous medication. Patient positioning is important to prevent
blood pressure changes or nerve damage associated
with abnormal position.
Patients are also monitored for pulse rate, respiration, blood pressure, and temperature. Additionally,
the heart is monitored using electrocardiography
(ECG). Ventilation is assessed using a pulse oximeter.
This machine is clipped with a special probe on one
finger and can measure the levels of oxygen and carbon dioxide, which are reliable indicators of respiratory status.

Aftercare
The major goal for recovery room monitoring is
assessment of residual drug effects. Recovery room
monitoring primarily focuses on heart stability,
respiratory adequacy and return to previous brain
functioning.
GALE ENCYCLOPEDIA OF MEDICINE

Sedation

For outpatient surgery there are two types of
sedation, conscious and unconscious sedation.
Patients receiving conscious sedation are capable of
rational responses, and they are able to maintain their
airway for ventilation. The hallmark of conscious
sedation is that it does not alter respiratory, cardiac,
or reflex functions (nerve reflexes from the brain) to
the level that requires external support for these vital
functions. Patients receiving conscious sedation are
cooperative, have stable vital signs (pulse, respiratory
rate, and temperature), shorter recovery room convalescence, and lower risk of developing drug-induced
complications. Unconscious sedation is a controlled
state of anesthesia, characterized by partial or complete loss of protective nerve reflexes, including the
ability to independently breathe and respond to
commands. The patient is unable to cooperate, has
labile (fluctuating) vital signs, prolonged recovery
room convalescence, and higher risk of anesthetic
complications.

KEY TERMS
Baseline— A return to an original state.
Diazepam— One of the most commonly used
sedative-hypnotic medications.

Risks
The original forms of diazepam (Valium, a very
common sedative) caused irritation of veins and phlebitis. Newer forms of diazepam (Dizac) are chemically
improved to lower the possibility of vein irritation.
Age and physical health are important risk factors.
Preexisting medical conditions such as high blood
pressure and heart and lung disease may increase the
chance of developing undesirable side effects.

Normal results
Normal or uncomplicated results for sedation
include alleviation of anxiety and discomfort.
Coupled with analgesic, patients are usually painfree. The normal progression post procedure or post
operatively would be to return to baseline brain functioning, unassisted breathing, and normal heart rate
and rhythm.

Abnormal results
Patients may have excessive nausea and vomiting
associated with narcotic analgesia (if this is indicated).
Excessive drowsiness can occur secondary to benzodiazepine-induced sedation. The patient can also
develop hypoventilation (a decrease in ventilation), airway obstruction, high or low blood pressure, abnormal
heart rhythms, nausea, vomiting, and shivering.
Resources
BOOKS

Fleisher, Gary R., et al. Textbook of Pediatric Emergency
Medicine. 4th ed. Lippincott Wlliams &Wilkins, 2000.
Miller, Ronald D., et al, editors. Anesthesia. 5th ed.
Churchill Livingstone, Inc., 2000.

Laith Farid Gulli, M.D.
Bilal Nasser, M.Sc.

Sedative-hypnotic drugs see Anti-insomnia
drugs
Sedimentation rate see Erythrocyte sedimentation rate
3327

Seizure disorder

Seizure disorder
Definition
A seizure is a sudden disruption of the brain’s
normal electrical activity accompanied by altered consciousness and/or other neurological and behavioral
manifestations. Epilepsy is a condition characterized
by recurrent seizures that may include repetitive muscle jerking called convulsions.

Description
There are more than 20 different seizure disorders.
One in ten Americans will have a seizure at some time,
and at least 200,000 have at least one seizure a month.
Epilepsy affects 1–2% of the population of the
United States. Although epilepsy is as common in
adults over 60 as in children under 10, 25% of all
cases develop before the age of five. One in every two
cases develops before the age of 25. About 125,000
new cases of epilepsy are diagnosed each year, and a
significant number of children and adults that have
not been diagnosed or treated have epilepsy.
Most seizures are benign, but a seizure that lasts a
long time can lead to status epilepticus, a life-threatening
condition characterized by continuous seizures, sustained loss of consciousness, and respiratory distress.
Non-convulsive epilepsy can impair physical coordination, vision, and other senses. Undiagnosed seizures
can lead to conditions that are more serious and more
difficult to manage.
Types of seizures
Generalized epileptic seizures occur when electrical abnormalities exist throughout the brain. A partial
seizure does not involve the entire brain. A partial
seizure begins in an area called an epileptic focus, but
may spread to other parts of the brain and cause a
generalized seizure. Some people who have epilepsy
have more than one type of seizure.
Motor attacks cause parts of the body to jerk
repeatedly. A motor attack usually lasts less than an
hour and may last only a few minutes. Sensory seizures
begin with numbness or tingling in one area. The sensation may move along one side of the body or the back
before subsiding.
Visual seizures, which affect the area of the brain
that controls sight, cause people to see things that are
not there. Auditory seizures affect the part of the brain
that controls hearing and cause the patient to imagine
voices, music, and other sounds. Other types of
3328

seizures can cause confusion, upset stomach, or emotional distress.
GENERALIZED SEIZURES. A generalized tonic-clonic (grand-mal) seizure begins with a loud cry before
the person having the seizure loses consciousness and
falls to the ground. The muscles become rigid for
about 30 seconds during the tonic phase of the seizure
and alternately contract and relax during the clonic
phase, which lasts 30–60 seconds. The skin sometimes
acquires a bluish tint and the person may bite his
tongue, lose bowel or bladder control, or have trouble
breathing.

A grand mal seizure lasts between two and five
minutes, and the person may be confused or have
trouble talking when he regains consciousness (postictal state). He may complain of head or muscle aches,
or weakness in his arms or legs before falling into a
deep sleep.
PRIMARY GENERALIZED SEIZURES. A primary generalized seizure occurs when electrical discharges
begin in both halves (hemispheres) of the brain at the
same time. Primary generalized seizures are more
likely to be major motor attacks than to be absence
seizures.
ABSENCE SEIZURES. Absence (petit mal) seizures
generally begin at about the age of four and stop by
the time the child becomes an adolescent.

Absence seizures usually begin with a brief loss of
consciousness and last between one and 10 seconds. A
person having a petit mal seizure becomes very quiet
and may blink, stare blankly, roll his eyes, or move his
lips. A petit mal seizure lasts 15-20 seconds. When it
ends, the person who had the seizure resumes whatever
he was doing before the seizure began. He will not
remember the seizure and may not realize that anything unusual has happened. Untreated, petit mal seizures can recur as many as 100 times a day and may
progress to grand mal seizures.
MYOCLONIC SEIZURES. Myoclonic seizures are
characterized by brief, involuntary spasms of the tongue or muscles of the face, arms, or legs. Myoclonic
seizures are most apt to occur when waking after a
night’s sleep.

A jacksonian seizure is a partial seizure characterized by tingling, stiffening, or jerking of an arm or leg.
Loss of consciousness is rare. The seizure may progress in characteristic fashion along the limb.
Limp posture and a brief period of unconsciousness are features of akinetic seizures, which occur in
young children. Akinetic seizures, which cause the
child to fall, also are called drop attacks.
GALE ENCYCLOPEDIA OF MEDICINE

Seizure disorder

PARTIAL SEIZURES. Simple partial seizures do not
spread from the focal area where they arise. Symptoms
are determined by the part of the brain affected. The
patient usually remains conscious during the seizure
and can later describe it in detail. In 2003, it was
reported that people who experience partial seizures
are twice as likely to have sleep disturbances as people
their same age and gender.
COMPLEX PARTIAL SEIZURES. A distinctive smell,
taste, or other unusual sensation (aura) may signal
the start of a complex partial seizure.

Complex partial seizures start as simple partial
seizures, but move beyond the focal area and cause
loss of consciousness. Complex partial seizures can
become major motor seizures. Although a person having a complex partial seizure may not seem to be
unconscious, he does not know what is happening
and may behave inappropriately. He will not remember the seizure, but may seem confused or intoxicated
for a few minutes after it ends.

Causes and symptoms
The origin of 50-70% of all cases of epilepsy is
unknown. Epilepsy sometimes is the result of trauma
at birth. Such causes include insufficient oxygen to the
brain; head injury; heavy bleeding or incompatibility
between a woman’s blood and the blood of her newborn baby; and infection immediately before, after, or
at the time of birth.
Other causes of epilepsy include:


head trauma resulting from a car accident, gunshot
wound, or other injury.



alcoholism



brain abscess or inflammation of membranes covering the brain or spinal cord



phenylketonuria (PKU, a disease that is present at
birth, often is characterized by seizures, and can
result in mental retardation) and other inherited
disorders



infectious diseases like measles, mumps, and
diphtheria



degenerative disease



lead poisoning, mercury poisoning, carbon monoxide
poisoning, or ingestion of some other poisonous
substance



genetic factors

Status epilepticus, a condition in which a person
suffers from continuous seizures and may have trouble
breathing, can be caused by:
GALE ENCYCLOPEDIA OF MEDICINE

This patient’s brain is exposed during surgery in order for
surgeons to remove the mass responsible for his epilepsy.
(Custom Medical Stock Photo. Reproduced by permission.)



suddenly discontinuing anti-seizure medication



hypoxic or metabolic encephalopathy (brain disease
resulting from lack of oxygen or malfunctioning of
other physical or chemical processes)



acute head injury



blood infection caused by inflammation of the brain
or the membranes that cover it

Diagnosis
Personal and family medical history, description
of seizure activity, and physical and neurological
examinations help primary care physicians, neurologists, and epileptologists diagnose this disorder.
Doctors rule out conditions that cause symptoms
that resemble epilepsy, including small strokes (transient ischemic attacks, or TIAs), fainting, (syncope),
pseudoseizures, and sleep attacks (narcolepsy.)
Neuropsychological testing uncovers learning or
memory problems. Neuroimaging provides views of
brain areas involved in seizure activity.
The electroencephalogram (EEG) is the main test
used to diagnose epilepsy. EEGs use electrodes placed
on or within the skull to record the brain’s electrical
activity and pinpoint the exact location of abnormal
discharges.
3329

Seizure disorder

The patient may be asked to remain motionless
during a short-term EEG or to go about his normal
activities during extended monitoring. Some patients
are deprived of sleep or exposed to seizure triggers,
such as rapid, deep breathing (hyperventilation) or
flashing lights (photic stimulation). In some cases,
people may be hospitalized for EEG monitorings
that can last as long as two weeks. Video EEGs also
document what the patient was doing when the seizure
occurred and how the seizure changed his behavior.
Other techniques used to diagnose epilepsy
include:


Magnetic resonance imaging (MRI), which provides
clear, detailed images of the brain. Functional MRI
(fMRI), performed while the patient does various
tasks, can measure shifts in electrical intensity and
blood flow and indicate which brain region each
activity affects.



Positron emission tomography (PET) and single
photon emission tomography (SPECT) monitor
blood flow and chemical activity in the brain area
being tested. PET and SPECT are very effective in
locating the brain region where metabolic changes
take place between seizures.

Treatment
The goal of epilepsy treatment is to eliminate
seizures or make the symptoms less frequent and less
severe. Long-term anticonvulsant drug therapy is the
most common form of epilepsy treatment.
Medication
A combination of drugs may be needed to control
some symptoms, but most patients who have epilepsy
take one of the following medications:


Dilantin (phenytoin)



Tegretol (carbamazepine)



Barbita (phenobarbital)



Mysoline (primidone)



Depakene (valproic acid, sodium valproate)



Klonopin (clonazepam)



Zarontin (ethosuximide).

Dilantin, Tegretol, Barbita, and Mysoline are
used to manage or control generalized tonic-clonic
and complex partial seizures. Depakene, Klonopin,
and Zarontin are prescribed for patients who have
absence seizures.
3330

Neurontin (gabapentin), Lamictal (lamotrigine),
and topiramate (Topamax) are among the medications more recently approved in the United States to
treat adults who have partial seizures or partial and
grand mal seizures. Another new medication called
Levetiracetam (Keppra) has been approved and
shows particularly good results in reducing partial
seizures among elderly patients with few side effects.
This is important, because elderly patients often have
other conditions and must take other medications that
might interact with seizure medications. In 2003,
Keppra’s manufacturer was working on a new antiepilectic drug from the same chemical family as
Keppra that should be more potent and effective.
Available medications frequently change, and it the
physician will determine the best treatment for an
individual patient. A 2003 report found that monotherapy, or using just one medication rather than a
combination, works better for most patients. The less
complicated the treatment, the more likely the patient
will comply and better manager the seizure disorder.
Even a patient whose seizures are well controlled
should have regular blood tests to measure levels of
anti-seizure medication in his system and to check to
see if the medication is causing any changes in his
blood or liver. A doctor should be notified if any
signs of drug toxicity appear, including uncontrolled
eye movements; sluggishness, dizziness, or hyperactivity; inability to see clearly or speak distinctly; nausea
or vomiting; or sleep problems.
Status epilepticus requires emergency treatment,
usually with Valium (Ativan), Dilantin, or Barbita. An
intravenous dextrose (sugar) solution is given to
patients whose condition is due to low blood sugar,
and a vitamin B1 preparation is administered intravenously when status epilepticus results from chronic
alcohol withdrawal. Because dextrose and thiamine
are essentially harmless and because delay in treatment can be disastrous, these medications are given
routinely, as it is usually difficult to obtain an adequate history from a patient suffering from status
epilepticus.
Intractable seizures are seizures that cannot be
controlled with medication or without sedation or
other unacceptable side effects. Surgery may be used
to eliminate or control intractable seizures.
Surgery
Surgery can be used to treat patients whose
intractable seizures stem from small focal lesions that
can be removed without endangering the patient,
changing the patient’s personality, dulling the
GALE ENCYCLOPEDIA OF MEDICINE



the best available anti-seizure medications have failed
to control the patient’s symptoms satisfactorily



the origin of the patient’s seizures has been precisely
located



there is good reason to believe that surgery will significantly improve the patient’s health and quality of life.

Every patient considering epilepsy surgery is carefully evaluated by one or more neurologists, neurosurgeons, neuropsychologists, and/or social workers. A
psychiatrist, chaplain, or other spiritual advisor may
help the patient and his family cope with the stress that
occurs during and after the selection process.
TYPES OF SURGERY. Surgical techniques used to
treat intractable epilepsy include:

This abstract artwork is based on a patient’s description of
what an epileptic seizure feels like. Epileptic seizures are
caused by chaotic electrical activity in the brain. They can
be triggered by a variety of factors, such as illness or stress,
although the underlying causes is not completely understood. (Illustration by John Bavosi, Photo Researchers, Inc.
Reproduced by permission.)



Lesionectomy. Removing the lesion (diseased brain
tissue) and some surrounding brain tissue is very
effective in controlling seizures. Lesionectomy is generally more successful than surgery performed on
patients whose seizures are not caused by clearly
defined lesions, but removing only part of the lesion
lessens the effectiveness of the procedure.



Temporal resections. Removing part of the temporal
lobe and the part of the brain associated with feelings, memory, and emotions (the hippocampus) provides good or excellent seizure control in 75-80% of
properly selected patients with appropriate types of
temporal lobe epilepsy. Some patients experience
post-operative speech and memory problems.



Extra-temporal resection. This procedure involves
removing some or all of the frontal lobe, the part of
the brain directly behind the forehead. The frontal
lobe helps regulate movement, planning, judgment,
and personality, and special care must be taken to
prevent post-operative problems with movement and
speech. Extra-temporal resection is most successful
in patients whose seizures are not widespread.



Hemispherectomy. This method of removing brain
tissue is restricted to patients with severe epilepsy and
abnormal discharges that often extend from one side
of the brain to the other. Hemispherectomies most
often are performed on infants or young children
who have had an extensive brain disease or disorder
since birth or from a very young age.



Corpus callosotomy. This procedure, an alternative
to hemispherectomy in patients with congenital
hemiplegia, removes some or all of the white matter
that separates the two halves of the brain. Corpus
callosotomy is performed almost exclusively on children who are frequently injured during falls caused

patient’s senses, or reducing the patient’s ability to
function.
Each year, as many as 5,000 new patients may
become suitable candidates for surgery, which most
often is performed at a comprehensive epilepsy center.
Potential surgical candidates include patients with:


partial seizures and secondarily generalized seizures
(attacks that begin in one area and spread to both
sides of the brain)



seizures and childhood paralysis on one side of the
body (hemiplegia)



complex partial seizures originating in the temporal
lobe (the part of the brain associated with speech,
hearing, and smell) or other focal seizures.
(However, the risk of surgery involving the speech
centers is that the patient will lose speech function.)



Generalized myoclonic seizures or generalized seizures featuring temporary paralysis (akinetic) or
loss of muscle tone (atonal)

A physical examination is conducted to verify that
a patient’s seizures are caused by epilepsy, and surgery
is not used to treat patients with severe psychiatric
disturbances or medical problems that raise risk factors to unacceptable levels.
GALE ENCYCLOPEDIA OF MEDICINE

3331

Seizure disorder

Surgery is never indicated unless:

Seizure disorder

by seizures. If removing two-thirds of the corpus
callosum doesn’t produce lasting improvement in
the patient’s condition, the remaining one-third will
be removed during another operation.


Multiple subpial transection. This procedure is used
to control the spread of seizures that originate in or
affect the ‘‘eloquent’’ cortex, the area of the brain
responsible for complex thought and reasoning.
Other forms of treatment

KETOGENIC DIET. A special high-fat, low-protein,
low-carbohydrate diet sometimes is used to treat
patients whose severe seizures have not responded to
other treatment. Calculated according to age, height,
and weight, the ketogenic diet induces mild starvation
and dehydration. This forces the body to create an
excessive supply of ketones, natural chemicals with
seizure-suppressing properties.

The goal of this controversial approach is to
maintain or improve seizure control while reducing
medication. The ketogenic diet works best with children between the ages of one and 10. It is introduced
over a period of several days, and most children are
hospitalized during the early stages of treatment.
If a child following this diet remains seizure-free
for at least six months, increased amounts of carbohydrates and protein gradually are added. If the child
shows no improvement after three months, the diet is
gradually discontinued. A 2003 study of the diet and
its effect on growth noted that If used, clinicians
should recommend adequate intake of energy and
protein and a higher proportion of unsaturated to
saturated dietary fats. The report also recommended
use of vitamin and mineral supplements with the diet.
Introduced in the 1920s, the ketogenic diet has
had limited, short-term success in controlling seizure
activity. Its use exposes patients to such potentially
harmful side effects as:


staphylococcal infections



atunted or delayed growth



low blood sugar (hypoglycemia)



excess fat in the blood (hyperlipidemia)



disease resulting from calcium deposits in the urinary
tract (urolithiasis)



disease of the optic nerve (optic neuropathy)

VAGUS NERVE STIMULATION. The United States
Food and Drug Administration (FDA) has approved
the use of vagus nerve stimulation (VNS) in patients
over the age of 16 who have intractable partial seizures.

3332

This non-surgical procedure uses a pacemaker-like
device implanted under the skin in the upper left chest,
to provide intermittent stimulation to the vagus nerve.
Stretching from the side of the neck into the brain, the
vagus nerve affects swallowing, speech, breathing, and
many other functions, and VNS may prevent or shorten
some seizures. A 2003 report said that this treatment
has reduced partial seizures by 50% or more in about
one-third of patient with no adverse effects.
First aid for seizures
A person having a seizure should not be
restrained, but sharp or dangerous objects should be
moved out of reach. Anyone having a complex partial
seizure can be warned away from danger by someone
calling his/her name in a clear, calm voice.
A person having a grand mal seizure should be
helped to lie down. Tight clothing should be loosened.
A soft, flat object like a towel or the palm of a hand
should be placed under the person’s head. Forcing a
hard object into the mouth of someone having a grand
mal seizure could cause injuries or breathing problems. If the person’s mouth is open, placing a folded
cloth or other soft object between his teeth will protect
his tongue. Turning his head to the side will help him
breathe. After a grand mal seizure has ended, the
person who had the seizure should be told what has
happened and reminded of where he is.

Alternative treatment
Stress increases seizure activity in 30% of people
who have epilepsy. Relaxation techniques can provide
some sense of control over the disorder, but they
should never be used instead of anti-seizure medication or used without the approval of the patient’s
doctor. Yoga, meditation, and favorite pastimes help
some people relax and manage stress more successfully. Biofeedback can teach adults and older adolescents how to recognize an aura and what to do to stop
its spread. Children under 14 are not usually able to
understand and apply principles of biofeedback.
Acupuncture treatments (acupuncture needles inserted
for a few minutes or left in place for as long as 30
minutes) make some people feel pleasantly relaxed.
Acupressure can have the same effect on children or
on adults who dislike needles.
Aromatherapy involves mixing aromatic plant oils
into water or other oils and massaging them into the
skin or using a special burner to waft their fragrance
throughout the room. Aromatherapy oils affect the
body and the brain, and undiluted oils should never
be applied directly to the skin. Ylang ylang, chamomile,
GALE ENCYCLOPEDIA OF MEDICINE

Acupressure—Needleless acupuncture.
Acupuncture—An ancient Chinese method of
relieving pain or treating illness by piercing specific
areas of the body with fine needles.
Biofeedback—A learning technique that helps
individuals influence automatic body functions.
Epileptologist—A physician who specializes in the
treatment of epilepsy.

or lavender can create a soothing mood. People who
have epilepsy should not use rosemary, hyssop, sage or
sweet fennel, which seem to make the brain more alert.
Dietary changes that emphasize whole foods and
eliminate processed foods may be helpful.
Homeopathic therapy also can work for people with
seizures, especially constitutional homeopathic treatment that acts at the deepest levels to address the needs
of the individual person.

Prognosis
People who have epilepsy have a higher-thanaverage rate of suicide; sudden, unexplained death;
and drowning and other accidental fatalities.
Benign focal epilepsy of childhood and some
absence seizures may disappear in time, but remission
is unlikely if seizures occur several times a day, several
times in a 48-hour period, or more frequently than in
the past.
Seizures that occur repeatedly over time and
always involve the same symptoms are called stereotypic seizures. The probability that stereotypic seizures will abate is poor.
About 85% of all seizure disorders can be partially or completely controlled if the patient takes antiseizure medication according to directions; avoids seizure-inducing sights, sounds, and other triggers; gets
enough sleep; and eats regular, balanced meals.
Anyone who has epilepsy should wear a bracelet
or necklace identifying his seizure disorder and listing
the medication he takes.

Prevention
Eating properly, getting enough sleep, and controlling stress and fevers can help prevent seizures. A
person who has epilepsy should be careful not to
GALE ENCYCLOPEDIA OF MEDICINE

hyperventilate. A person who experiences an aura
should find a safe place to lie down and stay there
until the seizure passes. Anticonvulsant medications
should not be stopped suddenly and, if other medications are prescribed or discontinued, the doctor treating the seizures should be notified. In some conditions,
such as severe head injury, brain surgery, or subarachnoid hemorrhage, anticonvulsant medications may be
given to the patient to prevent seizures.
Resources
PERIODICALS

Dilorio, Colleen, et al. ‘‘The Epilelpsy Medication and
Treatment Complexity Index: Reliability and Validity
Testing.’’ Journal of Neuroscience Nursing June 2003:
155–158.
‘‘Epilepsy Surgery and Vagus Nerve Stimulation Are
Effective When Drugs Fail.’’ Medical Devices &
Surgical Technology Week May 4, 2003: 33.
Finn, Robert. ‘‘Partial Seizures Double Risk of Sleep
Disturbances (Consider in Diagnosis, Management).’’
Clinical Psychiatry News June 2003: 36–-41.
Liu, Yeou-Mei Christiana, et al. ‘‘A Prospetive Study:
Growth and Nutritional Status of Children Treated
With the Ketogenic Diet.’’ Journal of the American
Dietetic Association June 2003: 707.
‘‘New Drug Candidate Shows Promise.’’ Clinical Trials
Week April 7, 2003: 26.
ORGANIZATIONS

American Epilepsy Society. 342 North Main Street, West
Hartford, CT 06117-2507. (860) 586-7505. <http://
www.aesnet.org>.
Epilepsy Concern International Service Group. 1282
Wynnewood Drive, West Palm Beach, FL 33417. (407)
683-0044.
Epilepsy Foundation of America. 4351 Garden City Drive,
Landover, MD 20785. (800) 332-1000. <http://
www.efa.org>.
Epilepsy Information Service. (800) 642-0500.

Maureen Haggerty
Teresa G. Odle

Selective abortion see Abortion, selective
Selective mutism see Mutism

Selective serotonin reuptake
inhibitors
Definition
Selective serotonin reuptake inhibitors are medicines that relieve symptoms of depression.
3333

Selective serotonin reuptake inhibitors

KEY TERMS

Selective serotonin reuptake inhibitors

Purpose
Selective serotonin reuptake inhibitors are used
to treat serious, continuing depression that interferes
with a person’s ability to function. Like other antidepressant drugs, they help reduce the extreme
sadness, hopelessness, and lack of interest in life
that are typical in people with depression. Selective
serotonin reuptake inhibitors also are used to treat
panic disorder, obsessive compulsive disorder (OCD),
and have shown promise for treating a variety of
other conditions, such as premenstrual syndrome, eating disorders, obesity, self-mutilation, and migraine
headache.
As of late 2003, SSRIs have been found to have
other off-label applications, including treatment of
premature ejaculation and diabetic neuropathy.

Description
Selective serotonin reuptake inhibitors, also
known as SSRIs or serotonin boosters, are thought
to work by correcting chemical imbalances in the
brain. Normally, chemicals called neurotransmitters
carry signals from one nerve cell to another. These
chemicals are constantly being released and taken
back up at the ends of nerve cells. Selective serotonin
reuptake inhibitors act on one particular neurotransmitter, serotonin, reducing its re-entry into nerve cells
and thus allowing serotonin to build up. Although
scientists are not exactly sure how it works, serotonin
is involved in the control of moods, as well as other
functions such as sleep, body temperature, and appetite for sweets and other carbohydrates. Somehow,
drugs that prevent the uptake of serotonin improve
the moods of people with serious depression, OCD,
and some types of anxiety disorders.
Selective serotonin reuptake inhibitors are available only with a doctor’s prescription and are sold in
tablet, capsule, and liquid forms. Commonly used
selective serotonin reuptake inhibitors are fluoxetine
(Prozac), paroxetine (Paxil), sertraline (Zoloft), and
fluvoxamine (Luvox).

Recommended dosage
The recommended dosage depends on the type of
SSRI and the type and severity of depression for
which it is being taken. Dosages may be different
for different people. It is important for people taking
SSRIs to take the drug exactly as prescribed. Taking
larger or more frequent doses or taking the drug for
longer than directed, for example, can cause
unwanted effects.
3334

SSRIs are about as effective as other antidepressants. About 60–80% of people taking the drugs as
directed will find that their conditions improve.
However, it may take four weeks or more for the
effects of this medicine to be felt. Therefore, when
people begin SSRI therapy, it is important to continue
taking the medication, even if an improvement in
mood doesn’t begin immediately.
People who take SSRIs should ask their doctors
about how to stop taking the medication. Usually,
doctors advise patients to taper down gradually to
reduce the chance of withdrawal symptoms or SSRI
discontinuation syndrome.
SSRIs may be taken with food to prevent stomach
upset.

Precautions
There have been reports that some patients taking
SSRIs have an increase in thoughts about suicide. It is
not clear whether the medicine causes this effect
because suicidal thoughts are very often a part of
depression itself. While some patients may experience
worsening of such thoughts early in the treatment of
their depression, there is no credible evidence that
SSRIs alone cause people to become suicidal or violent.
Serious and possibly life-threatening reactions may
occur when SSRIs are used in combination with monoamine oxidase inhibitors (MAO inhibitors), such as
Nardil and Parnate, which also are used to treat depression. These reactions also are possible when a person
stops taking an SSRI and immediately begins taking an
MAOI. SSRIs and MAO inhibitors should never be
taken at the same time. When switching from an SSRI
to an MAOI or vice versa, it may be necessary to allow
two to five weeks or more between stopping one and
starting the other. The physician prescribing the medications should tell the patient exactly how much time to
allow before beginning the other medication.
People with a history of manic disorders should
use any antidepressant, including an SSRI, with
caution.
It is important to see a doctor regularly while
taking SSRIs. The doctor will check to make sure the
medicine is working as it should and will watch for
unwanted side effects. The doctor may also need to
adjust the dosage during this period.
Some people feel drowsy, dizzy, or lightheaded
when using SSRIs. The drugs may also cause blurred
vision in some people. Since SSRIs can sometimes
cause drowsiness, driving or operating heavy
GALE ENCYCLOPEDIA OF MEDICINE

These medicines make some people feel lightheaded, dizzy, or faint when they get up after sitting
or lying down, a condition known as orthostatic hypotension. People may try to lessen the problem by getting
up gradually and holding onto something for support if
possible. If the problem is severe or doesn’t improve,
the patient should discuss it with his or her doctor.
Because SSRIs work on the central nervous system, they may add to the effects of alcohol and other
drugs that slow down the central nervous system, such
as antihistamines, cold medicine, allergy medicine,
sleep aids, medicine for seizures, tranquilizers, some
pain relievers, and muscle relaxants. They may also
add to the effects of anesthetics, including those used
for dental procedures. Anyone taking SSRIs should
check with his or her doctor before taking any of the
drugs mentioned above.
SSRIs may occasionally cause dry mouth, although
this side effect is much more common with an older
class of antidepressants known as tricyclics. To temporarily relieve the discomfort, doctors sometimes suggest chewing sugarless gum, sucking on sugarless candy
or ice chips, or using saliva substitutes, which come in
liquid and tablet forms and are available without a
prescription. If the problem continues for more than
two weeks, check with a doctor or dentist. Mouth dryness that continues over a long time may contribute to
tooth decay and other dental problems.
Changes in sexual functioning are among the
more common side effects with SSRIs. Depending on
the particular SSRI prescribed, 8–15% of patients
may report these side effects. The most common problem for men is delayed ejaculation. Women may be
unable to have orgasms. A doctor should be contacted
if any changes in sexual functioning occur.
Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if they
take SSRIs. Before taking these drugs, a patient should
let the doctor know about any of these conditions:
ALLERGIES. Anyone who has had unusual reactions to SSRIs in the past should let his or her doctor
know before taking the drugs again. The doctor
should also be told about any allergies to foods,
dyes, preservatives, or other substances.
PREGNANCY. In studies of laboratory animals,
some SSRIs have caused miscarriage and other

GALE ENCYCLOPEDIA OF MEDICINE

problems in pregnant females and their offspring.
However, at least two studies in humans (by
Pastuszak in 1993 and Kuhlin in 1998) have shown
SSRIs to be safe during pregnancy, and newer studies
done in 2003 have reported that SSRIs do not appear
to increase the risks of birth defects in the offspring.
Still, women who are pregnant or who may become
pregnant should check with their doctors before using
SSRIs.
BREASTFEEDING. SSRIs pass into breast milk and
some may occasionally cause unwanted side effects in
nursing babies whose mothers take the drugs. These
effects include vomiting, watery stools, crying, and
sleep problems. Women who are breastfeeding should
talk to their doctors about the use of SSRIs. They may
need to switch to a different medicine while breastfeeding. If SSRIs must be taken, it may be necessary to
stop breastfeeding while being treated with these
drugs. However, several studies in people (for example, Yoshida in 1998) have indicated that SSRIs in
breast milk have no effect on infant development.
DIABETES. SSRIs may affect blood sugar levels.
People with diabetes who notice changes in their
blood or urine tests while taking this medicine should
check with their doctors.
OTHER MEDICAL CONDITIONS. Before using
SSRIs, people with any of these medical problems
should make sure their doctors are aware of their
conditions: diabetes, kidney disease, liver disease, seizure disorders, current or past drug abuse or dependence, or diseases or conditions that affect the
metabolism or blood circulation.

Side effects
The most common side effects are anxiety and
nervousness (reported by 5–13% of people taking various SSRIs), tremor (5–14%), trouble sleeping (2–
8%), tiredness or weakness (4–15%), nausea (11–
26%), diarrhea (11–26%), constipation (1–8%), loss
of appetite (3–18%), weight loss (1–13%), dry mouth
(10–22%), headache (1–5%), sweating (5–9%), trouble urinating (1–2%), and decreased sexual ability (8–
15%). Many of these problems diminish or disappear
as the body adjusts to the drug and do not require
medical treatment unless they interfere with normal
activities. Persistent problems, such as sexual dysfunction, should be discussed with the doctor.
More serious side effects are possible, but extremely rare. People taking SSRIs who notice unusual
joint or muscle pain; breathing problems; chills or
fever; excessive excitement, fast talking, or actions
3335

Selective serotonin reuptake inhibitors

machinery should be undertaken cautiously, particularly when the person first begins taking the
medication.

Selective serotonin reuptake inhibitors

that are out of control; or mood swings should contact
their doctors. People who develop skin rashes or hives
after taking an SSRI should stop taking the medication and contact their doctors as soon as possible.
Other rare side effects may occur. Anyone who has
unusual symptoms after taking an SSRI should get in
touch with his or her doctor.
Side effects may continue for some time after
treatment with this medicine ends. How long the
effects continue depends on how long the drug was
taken and how much of it was used. In most cases,
doctors recommend that patients taper off SSRIs
rather than abruptly stopping them, because of the
risk of developing a condition known as SSRI discontinuation syndrome. This syndrome can mimic serious
illness. People who experience agitation, confusion, or
restlessness; dizziness or lightheadedness; vision problems; tremor; sleep problems; unusual tiredness or
weakness; nausea and vomiting or diarrhea; headache;
excessive sweating; runny nose; or muscle pain for
more than a few days after stopping or tapering an
SSRI should consult their doctors.

Interactions
SSRIs may interact with other medicines. When
this happens, the effects of one or both of the drugs
may change or the risk of side effects may be greater.
Anyone who takes SSRIs should let the doctor know
about all other medicines he or she is taking. Among
the drugs that may interact with SSRIs are:


such central nervous system (CNS) depressants as
medicine for allergies, colds, hay fever, and asthma;
sedatives; tranquilizers; prescription pain medicine;
muscle relaxants; medicine for seizures; sleep aids;
barbiturates; and anesthetics.



blood thinners (anticoagullants)



such monoamine oxidase inhibitors (MAOIs) as
Nardil or Parnate, used to treat conditions including
depression and Parkinson’s disease



the antiseizure drug phenytoin (Dilantin)



the food supplement (and sleep aid) tryptophan,
which has been withdrawn from the United States
market, but may be found in some herbal
preparations



digitalis and other heart medicines



St. John’s wort (Hypericum perforatum). St. John’s
wort is a herb used in Europe and the United States
to relieve mild-to-moderate symptoms of depression.
Research indicates that it acts as an SSRI and not as
an MAO inhibitor, as previously believed. People

3336

KEY TERMS
Anesthetic—Medicine that causes a loss of feeling,
especially of pain. Some anesthetics also cause a
loss of consciousness.
Anxiety—Worry or tension in response to real or
imagined stress, danger, or dreaded situations. Physical reactions, such as fast pulse, sweating, trembling,
fatigue, and weakness may accompany anxiety.
Central nervous system—The brain and spinal
cord.
Depression—A mental condition in which people
feel extremely sad and lose interest in life. People
with depression may also have sleep problems and
loss of appetite and may have trouble concentrating and carrying out everyday activities.
Metabolism—All the physical and chemical changes
that occur in cells to allow growth and maintain
body functions. These include processes that break
down substances to yield energy and processes
that build up other substances necessary for life.
Obsessive-compulsive disorder—An anxiety disorder in which people cannot prevent themselves
from dwelling on unwanted thoughts, acting on
urges, or performing repetitious rituals, such as
washing their hands or checking to make sure
they turned off the lights.
Off-label application—The use of a prescription
medication to treat conditions outside the indications approved by the Food and Drug
Administration (FDA).
Premenstrual syndrome—(PMS) A set of symptoms
that occur in some women 2–14 days before they
begin menstruating each month. Symptoms
include headache, fatigue, irritability, depression,
abdominal bloating, and breast tenderness.

who are using St. John’s wort to relieve depression
should not take a prescription SSRI at the same time.
The list above does not include every drug that may
interact with SSRIs. Patients should be sure to check
with a doctor or pharmacist before combining SSRIs
with any other prescription or nonprescription (overthe-counter) medicine, including herbal preparations.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Depression (Unipolar Disorder).’’ Section 15, Chapter
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Aronson, Sarah A., MD. ‘‘Depression.’’ eMedicine
December 31, 2003. <http://www.emedicine.com/
med/topic532.htm>.
Ditto, K. E. ‘‘SSRI Discontinuation Syndrome. Awareness
as an Approach to Prevention.’’ Postgraduate Medicine
114 (August 2003): 79–84.
Nonacs, R., and L. S. Cohen. ‘‘Assessment and Treatment of
Depression During Pregnancy: An Update.’’
Psychiatric Clinics of North America 26 (September
2003): 547–562.
Roose, S. P. ‘‘Treatment of Depression in Patients with
Heart Disease.’’ Biological Psychiatry 54 (August 1,
2003): 262–268.
Stone, K. J., A. J. Viera, and C. L. Parman. ‘‘Off-Label
Applications for SSRIs.’’ American Family Physician 68
(August 1, 2003): 425–427.
ORGANIZATIONS

American Psychiatric Association (APA). 1400 K Street,
NW, Washington, DC 20005. (888) 357-7924.
<http://www.psych.org>.
National Center for Complementary and Alternative
Medicine (NCCAM) Clearinghouse. P.O. Box 7923,
Gaithersburg, MD 20898-7923. (888) 644-6226.
<http://nccam.nih.gov>.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513.
<www.nimh.nih.gov.>.
U. S. Food and Drug Administration (FDA). 5600 Fishers
Lane, Rockville, MD 20857. (888) 463-6332.
<http://www.fda.gov>.

Nancy Ross-Flanigan
Rebecca J. Frey, PhD

biting, hitting, or bruising oneself; picking or pulling
at skin or hair; burning oneself with lighted cigarettes,
or amputating parts of the body.

Description
Self-mutilation has become a major public health
concern as its incidence appears to have risen since the
early 1990s. One source estimates that 0.75% of the
general American population practices self-mutilation. The incidence of self-mutilation is highest
among teenage females, patients diagnosed with borderline personality disorder, and patients diagnosed
with one of the dissociative disorders. Over half of selfmutilators were sexually abused as children, and many
also suffer from eating disorders.
Self-mutilation should not be confused with current fads for tattoos and body piercing. In some cases,
however, it may be difficult to distinguish between an
interest in these fads and the first indications of a
disorder.
The relationship of self-mutilation to suicide is
still debated even though statistics show that nearly
50% of individuals who injure themselves also
attempt suicide at some point in their lives. Many
researchers think that suicide attempts reflect feelings of rejection or hopelessness, while self-mutilation results from feelings of shame or a need to
relieve tension.

Causes and symptoms
Several different theories have been proposed to
explain self-mutilation:


self-mutilation is an outlet for strong negative emotions, especially anger or shame, that the person is
afraid to express in words or discuss with others.



self-mutilation represents anger at someone else
directed against the self.



self-mutilation relieves unbearable tension or anxiety
Many self-mutilators do report feeling relief after an
episode of self-cutting or other injury.



self-mutilation is a technique for triggering the
body’s biochemical responses to pain. Stress and
trauma release endorphins, which are the body’s
natural pain-killing substances



self-mutilation is a way of stopping a dissociative
episode. Dissociation is a process in which the mind
splits off, or dissociates, certain memories and
thoughts that are too painful to keep in conscious
awareness. Some people report that they feel

Self-mutilation
Definition
Self-mutilation is a general term for a variety of
forms of intentional self-harm without the wish to die.
Cutting one’s skin with razors or knives is the most
common pattern of self-mutilation. Others include
GALE ENCYCLOPEDIA OF MEDICINE

3337

Self-mutilation

189 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2002.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine,
Part I: Western Herbal Medicine. New York: Simon
and Schuster, 2002.
Pies, Ronald W. Handbook of Essential
Psychopharmacology. Washington, DC: American
Psychiatric Press, Inc.

Self-mutilation

‘‘numb’’ or ‘‘dead’’ when they dissociate, and selfinjury allows them to feel ‘‘alive.’’


self-mutilation is a symbolic acting-out of the larger culture’s mistreatment of women. This theory is
sometimes offered to explain why the great majority (about 75%) of self-mutilators are girls and
women

The symptoms of self-mutilation typically include
wearing long-sleeved or baggy clothing, even in hot
weather; and an unusual need for privacy. Self-mutilators are often hesitant to change their clothes or
undress around others. In most cases the person has
also shown signs of depression.

Diagnosis
Self-mutilation is usually diagnosed by a psychiatrist or psychotherapist. A family practitioner or nurse
who notices scars, bruises, or other physical evidence
of self-injury may refer the person to a specialist for
evaluation.

Treatment
Persons who mutilate themselves should seek
treatment from a therapist with some specialized training and experience with this behavior. Most self-mutilators are treated as outpatients, although there are
some inpatient programs, such as S.A.F.E., for adolescent females. A number of different treatment
approaches are used with self-mutilators, including
psychodynamic psychotherapy, group therapy, journaling, and behavioral therapy.
Although there are no medications specifically for
self-mutilation, antidepressants are often given, particularly if the patient meets the diagnostic criteria for a
depressive disorder.

Alternative treatment
Mindfulness training, which is a form of meditation, has been used to teach self-mutilators to observe
and identify their feelings in order to have some control over them.

Prognosis
The prognosis depends on the presence and severity of other emotional disorders, and a history of sexual abuse and/or suicide attempts. In general,
teenagers without a history of abuse or other disorders
have a good prognosis. Patients diagnosed with borderline personality disorder and/or a history of
3338

KEY TERMS
Borderline personality disorder (BPD)—A pattern
of behavior characterized by impulsive acts,
intense but chaotic relationships with others, identity problems, and emotional instability.
Dissociation—The splitting off of certain mental
processes from conscious awareness.
Dissociative disorders—A group of mental disorders in which dissociation is a prominent symptom.
Patients with dissociative disorders have a high rate
of self-mutilation.
Endorphins—Pain-killing substances produced in
the human body and released by stress or trauma.
Some researchers think that people who mutilate
themselves are trying to trigger the release of
endorphins.

attempted suicide are considered to have the worst
prognosis.

Prevention
Some society-wide factors that influence selfmutilation, such as the high rate of sexual abuse of
children and media stereotypes of women, are difficult to change. In general, however, young people
who have learned to express themselves in words
or through art and other creative activities are less
likely to deal with painful feelings by injuring their
bodies.
Resources
BOOKS

Eisendrath, Stuart J., M.D., and Jonathan E. Lichtmacher,
M.D. ‘‘Psychiatric Disorders.’’ In Current Medical
Diagnosis & Treatment 2001, edited by L. M. Tierney,
Jr., MD, et al., 40th ed. N. New York: Lange Medical
Books/McGraw-Hill, 2001.
ORGANIZATIONS

American Psychiatric Association. 1400 K Street, NW.
Washington, DC 20005. (202) 682-6220. <http://
www.psych.org>.
Focus Adolescent Services. (877) 362-8727. <http//
www.focusas.com>.
National Institute of Mental Health. 5600 Fishers Lane,
Rockville, MD 20857. (301) 443-4513. Fax: (301) 4434513. <http://www.nimh.nih.gov>.

Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Semen analysis evaluates a man’s sperm and
semen. It is done to discover cause for infertility and
to confirm success of vasectomy.

Purpose
Semen analysis is an initial step in investigating
why a couple has been unable to conceive a child.
Abnormalities of sperm and semen can cause male
infertility. Semen is the thick yellow-white male ejaculate containing sperm. Sperm are the male sex cells
that fertilize the female egg (ovum). They contain the
genetic information that the male will pass on to a
child.
Vasectomy is an operation done to sterilize a man
by stopping the release of sperm into semen. Success of
vasectomy is confirmed by the absence of sperm in
semen.

Description
The semen analysis test is usually done manually,
though computerized test systems are available. Many
laboratories base their procedures on standards published by the World Health Organization (WHO).
The volume of semen in the entire ejaculate is
measured. The appearance, color, thickness, and pH
is noted. A pH test looks at the range from a very acid
solution to a very alkaline solution. Semen, like many
other body fluids, has a standard pH range that would
be considered optimal for fertilization of the egg to
take place. The thick semen is then allowed to liquify;
this usually takes 20-60 minutes.
Drops of semen are placed on a microscope slide
and examined under the microscope. Motility, or
movement, of 100 sperm are observed and graded in
categories, such as rapid progressive or immotile.

Results of semen analysis for infertility must be
confirmed by a second analysis seven days to three
months after the first. Sperm counts may vary from
day to day.
Semen analysis to confirm success of vasectomy is
concerned only with discovering if sperm are still present. Semen is collected six weeks after surgery. If
sperm are seen, another specimen is collected 2 to 4
weeks later. The test is repeated until two consecutive
specimens are free of sperm.

Preparation
A man should collect an entire ejaculate, by masturbation, into a container provided by his physician.
To examine the best quality sperm, the specimen must
be collected after two to three days of sexual abstinence, but not more than five to seven days. The specimen must not come into contact with any spermicidal
agents used by a female partner for birth control purposes. The man should not have alcohol before the
test.
A semen specimen to investigate infertility must
be brought to the testing laboratory within one hour of
obtaining it. Timing is not as critical for the postvasectomy test but the semen must be kept at body
temperature. The most satisfactory sample is one
obtained in the lab rather than at home.

Normal results
WHO standards have established these normal
values:


volume less than or equal to 2.0 mL



sperm count greater than or equal to 20 million per
mL

The structure of sperm (sperm morphology) is
assessed by carefully examining sperm for abnormalities in the size and shape in the head, tail, and neck
regions. WHO standards define normal as a specimen
with less than 30% abnormal forms. An alternative
classification system (Kruger’s) measures the dimensions of sperm parts. Normal specimens are allowed
14% or less abnormalities.



motility (movement of the sperm) value is greater
than or equal to 50% with forward progression, or
greater than or equal to 25% with rapid progression
within 60 minutes of ejaculation



morphology greater than or equal to 30% with normal forms



white blood cell count less than 1 million per mL.

Sperm are counted by placing semen in a special
counting chamber. The sperm within the chamber are
counted under a microscope. White blood cells are

If infertility continues, despite normal semen analysis and female studies, further tests are done to evaluate sperm function.

GALE ENCYCLOPEDIA OF MEDICINE

3339

Semen analysis

Semen analysis

recorded; these may indicate a reproductive tract
infection. Laboratories may test for other biochemicals such as fructose, zinc, and citric acid. These are
believed to contribute to sperm health and fertility.

Seniors’ health

KEY TERMS
Infertility —The inability of a man and woman to
conceive a child after 12 months of unprotected
sexual intercourse.
Morphology—The size and shape of sperm.
Motility—The movement of sperm within the
semen.

Abnormal results
Abnormalities of semen volume and liquidity, and
sperm number and morphology decrease fertility.
These abnormalities may be inherited or caused by a
hormone imbalance, medications, or a recent infection. Further tests may be done to determine the
cause of abnormalities.
Resources
PERIODICALS

Kamada, M., et al. ‘‘Semen Analysis and Antisperm
Antibody.’’ Archives of Andrology March-April 1998):
117-128.

Nancy J. Nordenson

Senile tremor see Tremors

Seniors’ health
Definition
Seniors’ health refers to the physical and mental
conditions of senior citizens, those who are in their 60s
and older. The proportion of people age 65 years and
older in the United States is on the rise and will continue to increase through 2030.

Purpose
For a senior, the aging process and a person’s
lifestyle will affect health. People who maintain a
healthy weight, exercise regularly, eat nutritionally,
and don’t smoke reduce the risk for many health conditions. This wellness allows people to live longer and
to remain independent for more years. Smoking, obesity (excess weight), and lack of exercise shorten life
and increase the risk for many health conditions.
According to a 2003 report, about 80% of people in
3340

the United States age 65 and older have at least one
chronic (long-lasting) condition and 50% have two.
Diet and exercise
Proper diet and regular exercise form the foundation of senior health. A nutritional diet and physical
activity can help prevent diseases such as cancer,
stroke, heart disease, and diabetes. A healthy diet
also can help manage diabetes, high blood pressure,
and heart disease.
As people age, there is more of a need to exercise
on a regular basis. According to the American Heart
Association, the inactive person loses from 3–5% of
muscle fiber each decade after age 30. That loss would
total 30% of lost muscle fiber at age 60. Exercise helps
to boost muscle strength. It can help improve balance
and coordination, and therefore help to prevent falls.
Organizations including the heart association
advise that regular physical activity helps prevent
bone loss (osteoporosis) and the risk of conditions
such as heart disease, Type II diabetes, colon cancer,
stress, and depression. In addition, exercise can help
extend the lives of people with conditions such as
diabetes, high blood pressure, and high cholesterol.
Good health later in life helps to prevent serious illness
or death from common infections as well. If a senior
catches the flu, for instance, it can have more detrimental effects than in a healthier, younger person.
When the SARS outbreak occurred in 2002 and
2003, clinicians expressed concern about the elderly
Americans and again expressed the importance of diet
and exercise. As people age, their immune system
response weakens. Seniors need to be proactive in
keeping their systems strong.
Osteoporosis
Osteoporosis is a condition in which bones
become less dense (solid). Bones become brittle, thinner, and break easily. Although osteoporosis is associated with aging, it is only the risk of osteoporosis
that increases as a person ages. It is linked to approximately 70% of bone fractures in people age 46 and
older. According to the National Institutes of Health
(NIH), one out of two women over age 50 will experience an osteoporosis-related fracture. So will one out
of eight men over 50.
Osteoporosis is associated primarily with the
changes that occur to women during menopause.
During menopause, there is a decrease in the level of
estrogen, the hormone that helps maintain bone mass.
Other causes of osteoporosis include lack of exercise
and a diet deficient in vitamin D.
GALE ENCYCLOPEDIA OF MEDICINE

Osteoarthritis
Osteoarthritis is a joint disease in which cartilage
wears out and bones rub against each other. This
condition can occur gradually over time as activities
performed throughout the years cause wear on joints.
In addition, bones thin as a person ages.
Excess weight and injuries can aggravate this condition. About 16 million Americans experience some
form of osteoarthritis. It generally affects the neck,
fingers, lower back, knees, and toes. Symptoms
include pain, stiffness, swelling, and creaking. The
pain may disrupt sleep, and joint stiffness may make
it difficult for a person to dress.
Falls
More than two million Americans each year fall
and experience serious injuries, according to the
American Academy of Otolaryngology-Head and
Neck Surgery. For seniors, fall-related injuries can
reduce mobility and hinder independence.
As people age, their reflexes slow down so it may
be more difficult to prevent a fall. Deteriorating vision
and hearing can affect balance, which can cause an
accidental fall. Furthermore, conditions such as
arthritis, dizziness, and sleeping disorders can increase
the likelihood of a fall. In addition, a person may fall
at the start of a condition such as a stroke or heart
attack.
Falls can result in broken bones or fractures
because bones are weakened by osteoporosis. In addition, healing takes longer. Head injuries could affect
sight and hearing. Injuries sustained during falls could
reduce an active person’s mobility and independence.
Vision
Eyesight changes as people age. Generally, people
are in their 40s when they experience presbyopia, a
form of farsightedness. This is a progressive condition
involving a decrease in the eye’s ability to focus on
close objects (near vision). By age 65, little near focusing ability remains.
GALE ENCYCLOPEDIA OF MEDICINE

Glaucoma is a condition caused by pressure from
the build-up of a large amount of fluid in the eye. This
progressive condition is often seen in people in their
50s. It starts with the gradual loss of peripheral vision.
If not treated, it can lead to some vision loss.
People in their 60s may experience the first signs of
age-related macular degeneration (AMD). It is a progressive condition affecting the retina. The macula in
the retina distinguishes detail. Degeneration in the
macula could cause scarring and a gradual reduction
in vision. The person experiences a circle of blindness,
an area of sightlessness that grows as the condition
progress.
More than half of people age 65 or older will be
diagnosed with cataracts. Cataract refers to the loss of
the transparency in the lens of the eye. As the loss
progresses, the person is able to see less detail. This
condition generally affects both eyes.
Hearing
Presbycusis, age-related hearing loss, is a progressive condition. It usually starts with a difficulty in
hearing high-frequency sound such as people talking.
A senior has less trouble with low-frequency tones.
Background noise will make it even more difficult to
hear. Presbycusis affects approximately 25% of people
between the ages of 65 and 75 and half of those over
75. Many people diagnosed with this condition say
they have lost hearing in both ears. They also report
feelings of dizziness and that they experience a ringing
in their ears.
Sleep disorders
Sleep patterns change when a person ages. Many
people in their 60s and 70s experience less time in the
stages of deep sleep known as delta sleep. Despite this
change, many healthy older people don’t experience
sleep disorders. Overall health plays a role in whether a
senior experiences trouble sleeping.
Obesity is linked to snoring and sleep apnea.
Snoring can turn into apnea. A person with apnea
stops breathing for up to one minute until the brain
restarts the breathing process. This action could be
repeated several hundred times each night.
Furthermore, a senior’s sleep can be disrupted by
conditions such as arthritis, osteoporosis, and
Alzheimer’s disease. Insomnia, or the inability to stay
asleep, is a symptom of conditions including depression, anxiety, chronic pain, and restless leg syndrome
(RLS).
3341

Seniors’ health

Osteoporosis is largely preventable, however,
research released in 2003said that evidence is increasing to suggest that the condition starts as far back as in
the womb. If this is true, it still is preventable, but by
the behavior of the mother carrying a child. More
research needs to be done, but it is clear that childhood
growth rates are linked to hip fractures that occur
decades later.

Seniors’ health

RLS involves movement of legs when a person is
at rest. The person moves legs in response to a tingling
sensation in the upper leg, calf, or foot. In other cases,
legs move involuntarily. Sensations that trigger movement can re-occur within seconds.
A person with RLS is likely to have PLMD (periodic limb movement disorder). A sleeping person
with this condition will kick legs or move arms repeatedly. These involuntary movements can last from 20
seconds to an hour. Approximately 45% of the elderly
have a mild form of PLMD, according to the National
Sleep Foundation.
The cause of these disorders is not known. They
are thought to be caused by a chemical reaction in the
brain. In addition, the conditions may be hereditary.
Mental health
While age has little effect on the mind, social and
emotional factors affect an older person’s health.
After a lifetime of work or raising a family, retirement
brings several challenges. A person who has been
identified for years by a profession may experience a
sense of lost identity.
A senior may find that the thinking process has
changed. Learning something new may take longer.
However, older people have excellent recall of new
information.
Memory loss may be a concern, particularly since
this is a symptom of Alzheimer’s disease.

Leading causes of death in persons 65 and older

Cause of death

Number
of deaths

Death rate
(per
100,000
population)

Percentage
of all deaths
in those >65
years old

All causes
Heart disease
Malignant neoplasms,
including neoplasms
of lymphatic and
hematopoietic tissues
Cerebrovascular
diseases
Chronic obstructive
pulmonary disease
and associated
conditions
Pneumonia and
influenza
Diabetes mellitus
Accidents and
adverse effects
Motor vehicle accidents
All other accidents
and adverse effects
Nephritis, nephrotic
syndrome, and
nephrosis
Atherosclerosis
Septicemia
All other causes,
residual

1,542,493
594,858
345,387

4,963.2
1,914.0
1,111.3

100.0
38.6
22.4

125,409

403.5

8.1

72,755

234.1

4.7

70,485

226.8

4.6

35,523
26,213
7,210
19,003

114.3
84.3
23.2
61.1

2.3
1.7
0.5
1.2

17,306

55.7

1.1

17,158
15,351
222,048

55.2
49.4
2,045.9

1.1
1.0
14.4

Dementia
Alzheimer’s disease is a form of dementia, a condition in which mental abilities decline. Symptoms of
dementia include memory loss that goes beyond forgetting a word or where an item was placed. The person
with dementia may never recognize family members or
remember how to perform functions such as preparing a
meal. Sometimes they experience a change in personality, with some uncharacteristic aggression or paranoia.
Alzheimer’s disease is the most prevalent form of
dementia. Although the cause of this condition is not
known, the risk of Alzheimer’s increases as a person
ages. In 2000, the condition affected one in 15 people
over the age of 65. The ratio rises to one in three people
age 85 and older.
Alzheimer’s is a progressive condition. In most
cases, after five to eight years, a patient with this
condition is unable to perform basic functions. There
is no known cure for Alzheimer s. However, as of
2003, the U.S. Food and Drug Administration had
approved four medications that could help delay the
degenerative process.
3342

Precautions
A health condition may result in a doctor recommending against some forms of exercise. However,
even if a person can’t jog, other forms of exercise
include those designed for people in wheelchairs and
those who are bedridden.
Treatments for menopause and osteoporosis
include Raloxifene, a medication that may cause
blood clots.

Description
The cost of treatment varies. Cost of medical
treatment will be determined by the type of procedure
and whether a person has medical insurance. Health
plan and Medicare coverage and copayments impact
an individual’s cost for various preventions and
treatments.
GALE ENCYCLOPEDIA OF MEDICINE

Nutrition plays an important role in senior health.
Not only does a well-balanced diet keep a person from
becoming obese, that same diet is a safeguard against
health conditions that seniors face. Proper diet can
help prevent a condition like diabetes or keep it from
worsening.
The senior diet should consist of foods that are
low in fat, particularly saturated fat and cholesterol. A
person should choose foods that provide nutrients
such as iron and calcium. Other healthy menu choices
include:


fish, skinless poultry, and lean meat.



proteins such as dry beans (red beans, navy beans,
and soybeans), lentils, chickpeas, and peanuts.



low-fat dairy products



vegetables, especially those that are dark green and
leafy



citrus fruits or juices, melons, and berries



whole grains like wheat, rice, oats, corn, and barley



whole grain breads and cereals
Exercise

Physical activity should be rhythmic, repetitive,
and should challenge the circulatory system. It also
should be enjoyable so that a senior gets in the habit of
exercising regularly for 30 minutes each day. It may be
necessary to check with a doctor to determine the type
of exercise that can be done.
Walking is recommended for weight loss, stress
release, and many other conditions. Brisk walking is
said to produce the same benefits as jogging. Other
forms of exercise can include gardening, bicycling,
hiking, swimming, dancing, skating or ice-skating. If
weather prohibits outdoor activities, a person can
work out indoors with an exercise video.
Exercise also offers a chance to socialize. In some
cities, groups of seniors meet for regular walks at
shopping malls. Senior centers offer exercise classes
ranging from line dancing to belly dancing.
Costs for exercise range from the price of walking
shoes to the fees for joining a gym.

People should not smoke since smoking makes the
body produce less estrogen. Care should be taken to
avoid falling.
Diet should include from 1,000–1,300 mg. of calcium each day. Sources of calcium include:


leafy, dark-green vegetables such as spinach, kale,
mustard greens, and turnip greens



low-fat dairy products such as milk, yogurt, and
cheeses such as cheddar, Swiss, mozzarella, and parmesan; also helpful are foods made with milk such as
pudding and soup



canned fish such as salmon, sardine, and anchovies



tortillas made from lime-processed corn



tofu processed with calcium-sulfate



calcium and vitamin D tablets

MEDICAL TREATMENT. An x ray will indicate bone
loss when much of the density has decreased. A more
effective way of detecting osteoporosis is the DEXAscan (dual-energy x-ray absorbtiometry). This wholebody scan will indicate whether a person is at risk for
fractures. It could be useful for people at risk for
osteoporosis as well as women near the age of menopause or older. People should ask their doctors about
whether this test is needed.

During menopause, a woman loses estrogen. A
pill or skin patch containing estrogen and progesterone eases symptoms of menopause has been used to
treat osteoporosis. This treatment is known as hormone replacement therapy (HRT). In 2002, the
Women’s Health Initiative found that HRT produced
harmful effects in postmenopausal women, including
increased incidence of breast cancer, heart disease and
dementia. The effects were bad enough to stop the
study. In 2003, researchers were looking for alternatives to HRT for women who had been using the
hormones for osteoporosis. Until an alternative is
identified, women and physicians have been advised
to closely weigh the risks and benefits of hormone
therapy. Several drugs are available to help reduce
the risk of fractures in seniors with osteoporosis. In
2003, the FDA approved a new treatment option
called Teriparatide. Some alternative treatments
show promise in studies, including SAMe, (S-adenosylmethionine). However, long-term safety and effectiveness of SAMe have yet to be established.

Osteoporosis
Prevention is the best method of treating osteoporosis. Methods of preventing osteoporosis include
regular weight-bearing exercise such as walking, jogging, weight lifting, yoga, and stair climbing.
GALE ENCYCLOPEDIA OF MEDICINE

Osteoarthritis
Treatments for osteoarthritis range from preventative measures such as walking to joint replacement
surgery. Treatment costs vary from no cost for
3343

Seniors’ health

Nutrition

Seniors’ health

soaking a joint in cold water, the price of over-thecounter remedies to fees for surgery.
Preventive and maintenance remedies include
low-impact exercise such as swimming and walking,
along with maintaining proper posture. Nutritional
aids include foods rich in vitamin C such as citrus
fruits and broccoli. Also recommended is daily consumption of 400 international units of Vitamin E.
Cutting back on fats, sugar, salt, cholesterol, and
alcohol helps relieve the symptoms of osteoarthritis.
HOME REMEDIES AND PHYSICAL THERAPY. The
Arthritis Foundation recommends several remedies
for easing pain. To treat inflammation, a person
should use a cold treatment. Methods include soaking
the affected area in cold water or applying an ice pack.
To soothe aches and stimulate circulation, a person
applies heat to the affected area for 20 minutes. This
should be done three times a day.

Over-the-counter (OTC) remedies such as aspirin
and ibuprofen and salves containing capsaicin can be
helpful. Furthermore, a doctor may recommend antiinflammatory medications.
SURGICAL TREATMENT. If osteoarthritis is suspected, a doctor’s diagnosis will include an assessment
of whether joint pain is part of a patient’s medical
history. The doctor may take an x ray to determine
the presence of cartilage loss and how much degeneration occurred.

Acupuncture may be helpful in treating mild
osteoarthritis. Generally, a person should have one
to two treatments a week for several weeks. Afterward, one treatment is recommended. An assessment
of results should be made after 10 treatments.
In cases of severe osteoarthritis, joint replacement
surgery or joint immobilization may be required. Joints
are replaced with metal, plastic, or ceramic material.
Fall prevention
Fall prevention starts with regular exercise such as
walking. This improves balance and muscles. The
walk route should be on level ground. Other methods
for preventing falls include:


when rising from a chair or bed, a senior should
move slowly to avoid dizziness



people who smoke should quit



shoes with low heels and rubber soles are
recommended



medications should be monitored because of side
effects that increase the probability of a fall



vision and hearing should be checked periodically

3344



fall-proofing the home, including the installation of
lighting, especially on stairways, clearing clutter and
electrical cords that can cause falls, and installing
handrails and strips in bathtubs and rails on stairs.

MEDICAL TREATMENT FOR FALLS. After a fall, a
senior may need first aid treatment for cuts or fractures. The doctor may evaluate whether medications
cause balance problems. If indicated, the doctor may
examine the patient’s central nervous system function,
balance, and muscle/joint function. A hearing or
vision test may be ordered.

Corrective measures could include adjusting prescriptions, vision surgery or having the patient use a
cane or walker.
Vision
A person diagnosed with presbyopia may need
bifocals or reading glasses to read print that appears
too small. These lenses may need to be changed as
vision changes over the years. Eventually, a person
relies on glasses to focus on items that are near.
Other seniors who never needed corrective lenses
may need to wear eyeglasses. Publishers aware of this
condition produce books with large print.
A senior should schedule periodic vision exams
because early treatment helps prevent or lessen a risk
of cataracts or glaucoma. Diet also plays a role in
vision care. Dark green vegetables like broccoli are
said to help prevent cataracts from progressing.
Physical exercise is thought to reduce the pressure
associated with glaucoma.
Glaucoma can be treated with eyedrops. Surgery
can remove cataracts. The affected lens is removed
and replaced with a permanent synthetic lens called
an intraocular lens. There was no successful treatment
for age-related macular degeneration as of 2001.
Hearing
An audiologist can administer tests to determine
the amount of hearing loss. Although there is no cure
for presbycusis, hearing aids can help a senior affected
by age-related hearing loss. If this treatment is not
effective, the person might need to learn to read lips.
Sleep disorders
Losing weight can help with conditions such as
snoring and sleep apnea. A doctor may advise the
senior to quit smoking, reduce alcohol consumption,
or to sleep on his or her side. In some cases, a doctor
may refer the senior to a sleep disorder clinic. The
senior may be prescribed a continuous positive airway
GALE ENCYCLOPEDIA OF MEDICINE

PLMD and restless leg syndrome may be treated
with the prescription drug Dopar. These disorders
could be signs of kidney or circulation conditions.
Treatment of those conditions should end these sleeping disorders.
Insomnia treatments include exercising and treating depression, stress, and other causes of
sleeplessness.
Mental health
After retirement, a senior must find activities and
interests to provide a sense of fulfillment. Otherwise,
feelings of loneliness and isolation can lead to depression and susceptibility to poor health.
Activities that stimulate a person physically and
intellectually contribute to good health. A senior can
start an exercise program, take up hobbies, take classes,
or volunteer. Senior centers offer numerous activities.
Lunch programs provide nutritional meals and companionship. This is important because a senior living
alone may not feel motivated to prepare healthy meals.
Dementia
Diagnosis of Alzheimer’s disease starts with a
thorough medical examination. The doctor should
administer memory tests. Blood tests may be required,
as well as a CT scan or MRI scan of the brain. If
Alzheimer’s is diagnosed, the doctor may prescribe
medication to slow down progression of this form of
dementia.
As of 2003, the FDA had approved four prescription medications for treatment of Alzheimer’s.
Tacrine, donepezil, riviastigmine, and galantamine
are cholinesterase inhibitors that enhance memory.
Modest improvement was reported in clinical trials
on donepezil, riviastigmine, and galantamine.
Tacrine’s possible side effects include liver damage,
so it is seldom prescribed.

Preparation
Before beginning a weight loss or exercise program, seniors should check with their doctors. The
doctor will determine whether a patient is at a healthy
weight, or needs to gain or lose weight. The medical
professional should be informed about a health condition or a family history of a condition like heart
disease. The doctor may order a physical exam or
recommend a specific exercise program.
GALE ENCYCLOPEDIA OF MEDICINE

Exercise preparation
A senior should select a form of exercise enjoyable
enough to become a regular routine. Suitable clothing
or equipment such as walking shoes or a bicycle helmet
should be purchased. If a person is active for more
than a half-hour, the American Heart Association
recommends drinking water every 15 minutes.
In addition to packing a water bottle, a person
should pick an exercise buddy. Exercising with a friend
or a group makes the activity more enjoyable. In
addition, a person is more apt to stick with a routine
if a buddy is involved.
Before exercising, a warmup with slow stretching
exercises is recommended. This could take longer for
a senior because muscular elasticity slows down as
a person ages. The exercise session should end with a
cool-down that includes slow stretches.

Aftercare
Some recovery time may be needed after surgery.
However, a healthy person will heal more quickly. A
senior needs to maintain a schedule of regular exercise
in order to remain mobile. Otherwise, a minor illness
could make them dependent on others for daily care,
according to the American Heart Association.
If mobility becomes limited due to a condition
such as osteoarthritis, equipment like a walker and
devices that make it easier to open bottles and grip
cutlery can be helpful.

Risks
Exercising too long or too strenuously can be
physically harmful. The over-exertion could cause
the person to lose interest in exercise and put off
establishing a regular routine. Experts recommend
starting out slowly and building up to more intense
or longer sessions. This is particularly important for a
sedentary person.
Osteoporosis
The long-term effects of hormone replacement
therapy have ruled this treatment out for some women.

Normal results
Seniors who stay active and eat nutritionally will
be at less risk for conditions such as diabetes. A senior
also should seek mental stimulation and social interaction. These provide enjoyment, boost self-esteem,
and help reduce feelings of isolation and depression.
3345

Seniors’ health

pressure device. Known as a CPAP, the device is
placed over the nose. It sends air into the nose.

Sensory integration disorder

Although eyesight and hearing will weaken, glasses
and hearing aids help seniors keep the senses of sight
and hearing.
When surgery is required for osteoarthritis, hip
replacement surgery is extremely successful. In about
98% of surgeries, flexibility returns and pain is eased.
Knee replacement surgery also is effective.
If a person maintains a healthy lifestyle, the ability
to avoid falls and recover from them is increased.
After a fall, seniors needs to build up physical
strength and the confidence needed so they don’t fear
falling again. Care should be taken so that seniors
don’t feel isolated by their injuries. Isolation could
lead to decreased mobility and loss of independence.
There is no cure for Alzheimer’s disease. However,
several medications have proved moderately effective in
stopping memory loss. Since Alzheimer’s is progressive,
a person diagnosed with this condition should make
arrangements for the future. Finances should be taken
care of and plans should be made for future care.
Family should be brought into the discussion.
After diagnosis, a person should stay active for as
long as possible. Not only does this help with enjoying
this stage of life, activities can help to fight depression.
Alzheimer and other support groups can be helpful. In
addition, modifications to environment can be
effective.

Vernarec, Emil. ‘‘An Emerging Alternative to NSAIDs for
Osteoarthritis?’’ RN May 2003: 24-31.
ORGANIZATIONS

Alzheimer’s Association. 919 N. Michigan Ave., Suite 1100,
Chicago, IL 60611-1676. (800) 272-3900.
<http://www.alz.org>.
American Academy of Otolaryngology-Head and Neck
Surgery. One Prince St., Alexandria, VA 22314-3357.
(703) 836-4444. <http://www.ent.org>.
American Dietetic Association. 216 W. Jackson Blvd.,
Chicago, IL 60606-6995. (312) 8990040.<http://www.eatright.org>.
American Heart Association. 7272 Greenville Ave., Dallas,
TX75231. (800) AHA-USA1.
<http://www.americanheart.org>.
National Institute on Aging. P.O. Box 8057, Gaithersburg,
MD20898-8057. (800) 222-2225.
<http://www.nih.gov>.
National Osteoporosis Foundation. 1232 22nd St.,
NW,Washington, DC 20037. (800) 624-BONE.
<http://www.osteo.org>.
National Sleep Foundation. 1522 K St., NW, Suite
500Washington, DC 20005. Fax: (202) 3473472.<http://www.sleepfoundation.org>.

Liz Swain
Teresa G. Odle

Sensory hearing loss see Hearing loss

Resources
BOOKS

Gillick, Muriel R. Lifelines: Living Longer, Growing Frail,
Taking Heart. New York: W.W. Norton and Co., 2001.
Honn Qualls, Sara, and Norman Abeles, editors. Psychology
and the Aging Revolution: How We Adapt to Longer
Life. Washington, DC: American Psychological
Association, 2000.
Powell, Douglas H. The Nine Myths of Aging: Maximizing
the Quality of Later Life. Thorndike, ME: Thorndike
Press,1998.
Wei, Jeanne Y., and Sue Levkoff. Aging Well: The Complete
Guide to Physical and Emotional Health. New York:
Wiley, 2000.
PERIODICALS

‘‘Aging Americans Face Growing Health Threats.’’ Health
& Medicine Week June 23, 2003: 3.
Evans, Jeff. ‘‘Aging U.S. Population Will Force Changes in
Health Care Services.’’ Family Practice News April 1,
2003: 54-61.
‘‘Increasing Evidence That Osteoporosis Begins in the
Womb.’’ Womenós Health Weekly June 19, 2003: 30.
‘‘Update on the Treatment of Osteoporosis Released.’’ Drug
Week June 27, 2003: 344.
3346

Sensory integration disorder
Definition
Sensory integration disorder or dysfunction (SID)
is a neurological disorder that results from the brain’s
inability to integrate certain information received
from the body’s five basic sensory systems. These
sensory systems are responsible for detecting sights,
sounds, smell, tastes, temperatures, pain, and the position and movements of the body. The brain then forms
a combined picture of this information in order for the
body to make sense of its surroundings and react to
them appropriately. The ongoing relationship
between behavior and brain functioning is called sensory integration (SI), a theory that was first pioneered
by A. Jean Ayres, Ph.D., OTR in the 1960s.

Description
Sensory experiences include touch, movement,
body awareness, sight, sound, smell, taste, and the
pull of gravity. Distinguishing between these is the
GALE ENCYCLOPEDIA OF MEDICINE

The normal process of SI begins before birth and
continues throughout life, with the majority of SI
development occurring before the early teenage
years. The ability for SI to become more refined
and effective coincides with the aging process as it
determines how well motor and speech skills, and
emotional stability develop. The beginnings of the SI
theory by Ayres instigated ongoing research that looks
at the crucial foundation it provides for complex
learning and behavior throughout life.

Causes and symptoms
The presence of a sensory integration disorder is
typically detected in young children. While most
children develop SI during the course of ordinary
childhood activities, which helps establish such things
as the ability for motor planning and adapting to
incoming sensations, others’ SI ability does not
develop as efficiently. When their process is disordered, a variety of problems in learning, development,
or behavior become obvious.
Those who have sensory integration dysfunction
may be unable to respond to certain sensory information by planning and organizing what needs to be done
in an appropriate and automatic manner. This may
cause a primitive survival technique called ‘‘fright,
flight, and fight,’’ or withdrawal response, which
originates from the ‘‘primitive’’ brain. This response
often appears extreme and inappropriate for the
particular situation.
The neurological disorganization resulting in SID
occurs in three different ways: the brain does not
receive messages due to a disconnection in the neuron
cells; sensory messages are received inconsistently; or
sensory messages are received consistently, but do not
connect properly with other sensory messages. When
the brain poorly processes sensory messages, inefficient motor, language, or emotional output is the
result.
According to Sensory Integration International
(SII), a non-profit corporation concerned with the
impact of sensory integrative problems on people’s
lives, the following are some signs of sensory integration disorder (SID):
GALE ENCYCLOPEDIA OF MEDICINE



oversensitivity to touch, movement, sights, or sounds



underreactivity to touch, movement, sights, or
sounds



tendency to be easily distracted



social and/or emotional problems



activity level that is unusually high or unusually low



physical clumsiness or apparent carelessness



impulsive, lacking in self-control



difficulty in making transitions from one situation to
another



inability to unwind or calm self



poor self concept



delays in speech, language, or motor skills



delays in academic achievement

While research indicates that sensory integrative
problems are found in up to 70% of children who are
considered learning disabled by schools, the problems
of sensory integration are not confined to children
with learning disabilities. SID transfers through all
age groups, as well as intellectual levels and socioeconomic groups. Factors that contribute to SID include:
premature birth; autism and other developmental
disorders; learning disabilities; delinquency and
substance abuse due to learning disabilities; stressrelated disorders; and brain injury. Two of the biggest
contributing conditions are autism and attentiondeficit hyperactivity disorder (ADHD).

Diagnosis
In order to determine the presence of SID, an
evaluation may be conducted by a qualified occupational or physical therapist. An evaluation normally
consists of both standardized testing and structured
observations of responses to sensory stimulation,
posture, balance, coordination, and eye movements.
These test results and assessment data, along with
information from other professionals and parents,
are carefully analyzed by the therapist who then
makes
recommendations
about
appropriate
treatment.

Treatment
Occupational therapists play a key role in the
conventional treatment of SID. By providing sensory
integration therapy, occupational therapists are able
to supply the vital sensory input and experiences that
children with SID need to grow and learn. Also
referred to as a ‘‘sensory diet,’’ this type of therapy
3347

Sensory integration disorder

process of sensory integration (SI). While the process
of SI occurs automatically and without effort for
most, for some the process is inefficient. Extensive
effort and attention are required in these individuals
for SI to occur, without a guarantee of it being accomplished. When this happens, goals are not easily completed, resulting in sensory integration disorder (SID).

Sensory integration disorder

involves a planned and scheduled activity program
implemented by an occupational therapist, with each
‘‘diet’’ being designed and developed to meet the needs
of the child’s nervous system. A sensory diet stimulates
the ‘‘near’’ senses (tactile, vestibular, and proprioceptive) with a combination of alerting, organizing, and
calming techniques.
Motor skills training methods that normally consist of adaptive physical education, movement education, and gymnastics are often used by occupational
and physical therapists. While these are important
skills to work on, the sensory integrative approach is
vital to treating SID.
The sensory integrative approach is guided by one
important aspect—the child’s motivation in selection
of the activities. By allowing them to be actively
involved, and explore activities that provide sensory
experiences most beneficial to them, children become
more mature and efficient at organizing sensory
information.

KEY TERMS
Axon—A process of a neuron that conducts
impulses away from the cell body. Axons are
usually long and straight.
Cortical—Regarding the cortex, or the outer layer of
the brain, as distinguished from the inner portion.
Neurotransmission—When a neurotransmitter, or
chemical agent released by a particular brain cell,
travels across the synapse to act on the target cell to
either inhibit or excite it.
Proprioceptive—Pertaining to proprioception, or
the awareness of posture, movement, and changes
in equilibrium and the knowledge of position, weight,
and resistance of objects as they relate to the body.
Tactile—The perception of touch.
Vestibular—Pertaining to the vestibule; regarding
the vestibular nerve of the ear which is linked to the
ability to hear sounds.

Alternative treatment
Sensory integration disorder (SID) is treatable
with occupational therapy, but some alternative methods are emerging to complement the conventional
methods used for SID.
Therapeutic body brushing is often used on children (not infants) who overreact to tactile stimulation.
A specific non-scratching surgical brush is used to
make firm, brisk movements over most of the body,
especially the arms, legs, hands, back and soles of the
feet. A technique of deep joint compression follows the
brushing. Usually begun by an occupational therapist,
the technique is taught to parents who need to complete the process for three to five minutes, six to eight
times a day. The time needed for brushing is reduced
as the child begins to respond more normally to touch.
In order for this therapy to be effective, the correct
brush and technique must be used.
A report in 1998 indicated the use of cerebral
electrical stimulation (CES) as being helpful to children with conditions such as moderate to severe
autistic spectrum disorders, learning disabilities,
and sensory integration dysfunction. CES is a modification of Transcutaneous Electrical Nerve
Stimulation (TENS) technology that has been used
to treat adults with various pain problems, including
arthritis and carpal tunnel syndrome. TENS therapy
uses a low voltage signal applied to the body through
the skin with the goal of replacing painful impressions with a massage-like sensation. A much lower
3348

signal is used for CES than that used for traditional
TENS, and the electrodes are placed on the scalp or
ears. Occupational therapists who have studied the
use of CES suggest that CES for children with SID
can result in improved brain activity. The device is
worn by children at home for 10 minutes at a time,
twice per day.
Music therapy helps promote active listening.
Hypnosis and biofeedback are sometimes used, along
with psychotherapy, to help those with SID, particularly older patients.

Prognosis
By providing treatment at an early age, sensory
integration disorder may be managed successfully.
The ultimate goal is for the individual to be better
able to interact with his or her environment in a
more successful and adaptive way.
Resources
ORGANIZATIONS

Sensory Integration International/The Ayres Clinic. 1514
Cabrillo Avenue, Torrance, CA 90501-2817.
OTHER

Sensory Integration Dysfunction. <http://home.ptd.net/
blnelson/SIDEWEBPAGE2.htm>.
Sensory Integration International. <http://
www.sensoryint.com>.
GALE ENCYCLOPEDIA OF MEDICINE

Sepsis

Sensory Integration Network. <http://
www.sinetwork.org>.
Southpaw Enterprises, Inc. <http://
www.southpawenterprises.com>.

KEY TERMS
Bacteremia—The medical term for sepsis.
Beth A. Kapes

Sepsis
Definition
Sepsis refers to a bacterial infection in the bloodstream or body tissues. This is a very broad term
covering the presence of many types of microscopic
disease-causing organisms.

Description
Sepsis is also called bacteremia. Closely related
terms include septicemia and septic syndrome. In the
general population, the incidence of sepsis is two people in 10,000. The number of deaths from sepsis each
year has almost doubled in the United States since
1980 because more patients are developing the condition. There are three major factors responsible for
this increase: a rise in the number of organ transplants
and other surgical procedures that require suppressing
the patient’s immune system; the greater number of
elderly people in the population; and the overuse of
antibiotics to treat infectious illnesses, resulting in the
development of drug-resistant bacteria.

Causes and symptoms
Sepsis can originate anywhere bacteria can gain
entry to the body; common sites include the genitourinary tract, the liver and its bile ducts, the gastrointestinal tract, and the lungs. Broken or ulcerated skin can
also provide access to bacteria commonly present in
the environment. Invasive medical procedures, including dental work, can introduce bacteria or permit them
to accumulate in the body. Entry points and equipment left in place for any length of time present a
particular risk. Heart valve replacement, catheters, ostomy sites, intravenous (IV) or arterial lines, surgical
wounds, or surgical drains are examples. IV drug users
are at high risk as well.
People with inefficient immune systems, HIV
infection, spinal cord injuries, or blood disorders are
at particular risk for sepsis and have a higher death
rate (up to 60%); in people who have no underlying
GALE ENCYCLOPEDIA OF MEDICINE

Prophylactic—Referring to medications or other
treatments given to prevent disease.

chronic disease, the death rate is far lower (about 5%).
The growing problem of antibiotic resistance has
increased the incidence of sepsis, partly because ordinary preventive measures (such as prophylactic antibiotics) are less effective.
Cancer patients are at an increased risk of developing sepsis because chemotherapy and other forms of
treatment for cancer weaken their immune systems.
The most common symptom of sepsis is fever,
often accompanied by chills or shaking, or other flulike symptoms. A history of any recent invasive procedure or dental work should raise the suspicion of
sepsis and medical help should be sought.

Diagnosis
The presence of sepsis is indicated by blood tests
showing particularly high or low white blood cell counts.
The causative agent is determined by blood culture.
In some cases the doctor may order imaging studies
to rule out pneumonia, or to determine whether the
sepsis has developed from a ruptured appendix or
other leakage from the digestive tract into the abdomen.

Treatment
Identifying the specific causative agent ultimately
determines how sepsis is treated. However, time is of
the essence, so a broad-spectrum antibiotic or multiple
antibiotics will be administered until blood cultures
reveal the culprit and treatment can be made specific
to the organism. Intravenous antibiotic therapy is
usually necessary and is administered in the hospital.
The patient’s chances of survival are increased by
rapid admission to an intensive care unit followed by
aggressive treatment with antibiotics.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Bacteremia and Septic Shock.’’ Section 13, Chapter
156 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
3349

Septic shock

Description

PERIODICALS

Cunha, Burke A., MD. ‘‘Sepsis, Bacterial.’’ eMedicine
September 29, 2004. <http://www.emedicine.com/
med/topic3163.htm>.
Koranyi, K. I., and M. A. Ranalli. ‘‘Mycobacterium aurum
Bacteremia in an Immunocompromised Child.’’
Pediatric Infectious Diseases Journal 22 (December
2003): 1108–1109.
Larche, J., E. Azoulay, F. Fieux, et al. ‘‘Improved Survival
of Critically Ill Cancer Patients with Septic Shock.’’
Intensive Care Medicine 29 (October 2003): 1688–1695.
Paphitou, N. I., and K. V. Rolston. ‘‘Catheter-Related
Bacteremia Caused by Agrobacterium radiobacter in a
Cancer Patient: Case Report and Literature Review.’’
Infection 31 (December 2003): 421–424.
Petrosillo, N., L. Pagani, G. Ippolito, et al. ‘‘Nosocomial
Infections in HIV-Positive Patients: An Overview.’’
Infection 31, Supplement 2 (December 2003): 28–34.
Wall, B. M., T. Mangold, K. M. Huch, et al. ‘‘Bacteremia in
the Chronic Spinal Cord Injury Population: Risk
Factors for Mortality.’’ Journal of Spinal Cord Medicine
26 (Fall 2003): 248–253.
ORGANIZATIONS

American College of Epidemiology. 1500 Sunday Drive,
Suite 102, Raleigh, NC 27607. (919) 861-5573.
<http://www.acepidemiology.org>.
American Public Health Association (APHA). 800 I Street
NW, Washington, DC 20001-3710. (202) 777-APHA.
<http://www.apha.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.
OTHER

‘‘Supportive Care for Patients—Fever, Chills, and Sweats.’’
National Cancer Institute CancerNet 16 April 16, 2001.
<http://cancernet.nci.nih.gov/coping.html>.

Jill S. Lasker
Rebecca J. Frey, PhD

Sepsis syndrome see Septic shock
Septal deviation see Deviated septum
Septic arthritis see Infectious arthritis

Septic shock
Definition
Septic shock is a potentially lethal drop in blood
pressure due to the presence of bacteria in the blood.
3350

Septic shock is a possible consequence of bacteremia, or bacteria in the bloodstream. Bacterial toxins,
and the immune system response to them, cause a
dramatic drop in blood pressure, preventing the delivery of blood to the organs. Septic shock can lead to
multiple organ failure including respiratory failure,
and may cause rapid death. Toxic shock syndrome is
one type of septic shock.

Causes and symptoms
During an infection, certain types of bacteria can
produce and release complex molecules, called endotoxins, that may provoke a dramatic response by the
body’s immune system. Released in the bloodstream,
endotoxins are particularly dangerous, because they
become widely dispersed and affect the blood vessels
themselves. Arteries and the smaller arterioles open
wider, increasing the total volume of the circulatory
system. At the same time, the walls of the blood vessels
become leaky, allowing fluid to seep out into the tissues, lowering the amount of fluid left in circulation.
This combination of increased system volume and
decreased fluid causes a dramatic decrease in blood
pressure and reduces the blood flow to the organs.
Other changes brought on by immune response may
cause coagulation of the blood in the extremities,
which can further decrease circulation through the
organs.
Septic shock is seen most often in patients with
suppressed immune systems, and is usually due to
bacteria acquired during treatment at the hospital.
The immune system is suppressed by drugs used
to treat cancer, autoimmune disorders, organ transplants, and diseases of immune deficiency such as
AIDS. Malnutrition, chronic drug abuse, and longterm illness increase the likelihood of succumbing
to bacterial infection. Bacteremia is more likely
with preexisting infections such as urinary or gastrointestinal tract infections, or skin ulcers.
Bacteria may be introduced to the blood stream by
surgical procedures, catheters, or intravenous
equipment.
Toxic shock syndrome most often occurs in menstruating women using highly absorbent tampons.
Left in place longer than other types, these tampons
provide the breeding ground for Staphylococcus
bacteria, which may then enter the bloodstream
through small tears in the vaginal lining. The incidence of toxic shock syndrome has declined markedly since this type of tampon was withdrawn from
the market.
GALE ENCYCLOPEDIA OF MEDICINE

Septic shock is usually preceded by bacteremia,
which is marked by fever, malaise, chills, and nausea.
The first sign of shock is often confusion and
decreased consciousness. In this beginning stage, the
extremities are usually warm. Later, they become cool,
pale, and bluish. Fever may give way to lower than
normal temperatures later on in sepsis.
Other symptoms include:


rapid heartbeat



shallow, rapid breathing



decreased urination.



reddish patches in the skin

Septic shock may progress to cause ‘‘adult respiratory distress syndrome,’’ in which fluid collects in the
lungs, and breathing becomes very shallow and
labored. This condition may lead to ventilatory collapse, in which the patient can no longer breathe adequately without assistance.

Diagnosis
Diagnosis of septic shock is made by measuring
blood pressure, heart rate, and respiration rate, as well
as by a consideration of possible sources of infection.
Blood pressure may be monitored with a catheter
device inserted into the pulmonary artery supplying
the lungs (Swan-Ganz catheter). Blood cultures are
done to determine the type of bacteria responsible.
The levels of oxygen, carbon dioxide, and acidity in
the blood are also monitored to assess changes in
respiratory function.

KEY TERMS
Bacteremia—Invasion of the bloodstream by
bacteria.

Prognosis
Septic shock is most likely to develop in the hospital, since it follows infections which are likely to be
the objects of treatment. Because of this, careful monitoring and early, aggressive therapy can minimize the
likelihood of progression. Nonetheless, death occurs
in at least 25% of all cases.
The likelihood of recovery from septic shock
depends on may factors, including the degree of
immunosuppression of the patient, underlying disease, promptness of treatment, and type of bacteria
responsible. Mortality is highest in the very young
and the elderly, those with persistent or recurrent
infection, and those with compromised immune
systems.

Prevention
The risk of developing septic shock can be minimized through treatment of underlying bacterial infections, and prompt attention to signs of bacteremia. In
the hospital, scrupulous aseptic technique on the part
of medical professionals lowers the risk of introducing
bacteria into the bloodstream.
Resources
OTHER

Treatment
Septic shock is treated initially with a combination of antibiotics and fluid replacement. The antibiotic is chosen based on the bacteria present, although
two or more types of antibiotics may be used initially
until the organism is identified. Intravenous fluids,
either blood or protein solutions, replace the fluid
lost by leakage. Coagulation and hemorrhage may be
treated with transfusions of plasma or platelets.
Dopamine may be given to increase blood pressure
further if necessary.
Respiratory distress is treated with mechanical
ventilation and supplemental oxygen, either using a
nosepiece or a tube into the trachea through the throat.
Identification and treatment of the primary infection site is important to prevent ongoing proliferation
of bacteria.
GALE ENCYCLOPEDIA OF MEDICINE

The Merck Page. April 13, 1998. <http://
www.merck.com>.

Richard Robinson

Septoplasty
Definition
Septoplasty is a surgical procedure to correct the
shape of the septum of the nose. The nasal septum is
the separation between the two nostrils. In adults, the
septum is composed partly of cartilage and partly of
bone.
3351

Septoplasty

Symptoms

Septoplasty

Purpose
Septoplasty is performed to correct a crooked
(deviated) or dislocated septum, often as part of plastic
surgery of the nose (rhinoplasty). The nasal septum has
three functions: to support the nose, regulate air flow,
and support the mucous membranes (mucosa) of the
nose. Septoplasty is done to correct the shape of the
nose caused by a deformed septum or correct deregulated air flow caused by a deviated septum. Septoplasty
is often needed when the patient is having an operation
to reduce the size of the nose (reductive rhinoplasty),
because this operation usually reduces the amount of
breathing space in the nose.
Septoplasty may also be done as a follow-up
procedure following facial trauma, as the nose is
frequently broken or dislocated by blows to the face
resulting from automobile accidents, criminal
assaults, or sports injuries.

Precautions
Septoplasty is ordinarily not performed within six
months of a traumatic injury to the nose.

Description
Septoplasties are performed in the hospital with a
combination of local and intravenous anesthesia. In
some cases, hypnosis has been successfully used as
anesthesia. After the patient is anesthetized, the surgeon makes a cut (incision) in the mucous tissue that
covers the part of the septum that is made of cartilage.
The tissue is lifted, exposing the cartilage and bony
part of the septum. Usually, one side of the mucous
tissue is left intact to provide support during healing.
Cartilage is cut away as needed.
As the surgeon cuts away the cartilage, deformities tend to straighten themselves out, reducing the
amount of cartilage that must be cut. Once the cartilage is cut, bony deformities can be corrected. For
most patients, this is the extent of the surgery required
to improve breathing through the nose and correct
deformities. Some patients have bony obstructions at
the base of the nasal chamber and require further
surgery. These obstructions include bony spurs and
ridges that contribute to drying, ulceration, or bleeding of the mucous tissue that covers the inside of the
nasal passages. In these cases, the extent of the surgery
depends on the nature of the deformities that need
correcting.
During surgery, the patient’s own cartilage that
has been removed can be reused to provide support for
3352

KEY TERMS
Cartilage—A tough, elastic connective tissue found
in the joints, outer ear, nose, larynx, and other parts
of the body.
Rhinoplasty—Plastic surgery of the nose.
Septum (plural, septa)—The dividing partition in
the nose that separates the two nostrils. It is composed of bone and cartilage.
Splint—A thin piece of rigid material that is sometimes used during nasal surgery to hold certain
structures in place until healing is underway.

the nose if needed. External septum supports are not
usually needed. Splints may be needed occasionally to
support cartilage when extensive cutting has been
done. External splints can be used to support the
cartilage for the first few days of healing. Tefla gauze
is inserted in the nostril to support the flaps and
cartilage and to absorb any bleeding or mucus.
A newer option for closing perforations in the
septum is a button made of Silastic, a compound of
silicone and rubber.

Preparation
Before performing a septoplasty, the surgeon will
evaluate the difference in airflow between the two
nostrils. In children, this assessment can be done very
simply by asking the child to breathe out slowly on a
small mirror held in front of the nose.
As with any other operation under general
anesthesia, patients are evaluated for any physical
conditions that might complicate surgery and for any
medications that might affect blood clotting time.

Aftercare
Patients with septoplasties are usually sent home
from the hospital later the same day or the morning
after the surgery. All dressings inside the nose are
removed before the patient leaves. Aftercare includes
a list of detailed instructions for the patient that focus
on preventing trauma to the nose.

Risks
The risks from a septoplasty are similar to those
from other operations on the face: postoperative
pain with some bleeding, swelling, bruising, or
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Normal results include improved breathing and
airflow through the nostrils, and an acceptable outward shape of the nose.
Resources

Serum sickness
Definition
Serum sickness is a type of delayed allergic
response, appearing four to 10 days after exposure to
some antibiotics or antiserum, the portion of serum
that contains antibodies, such as gamma globulin,
which may be given to provide immunization against
some diseases.

Description

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Septal Deviation and Perforation.’’ Section 7, Chapter
86 In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Piatti, G., A. Scotti, and U. Ambrosetti. ‘‘Nasal Ciliary Beat
after Insertion of Septo-Valvular Splints.’’
Otolaryngology and Head and Neck Surgery 130 (May
2004): 558–562.
Wain, H. J. ‘‘Reflections on Hypnotizability and Its Impact
on Successful Surgical Hypnosis: A Sole Anesthetic for
Septoplasty.’’ American Journal of Clinical Hypnosis 46
(April 2004): 313–321.

Serum sickness is very similar to an allergic reaction. The patient’s immune system recognizes the
proteins in the drug or antiserum as foreign proteins,
and produces its own antibodies to protect against the
foreign proteins. The newly formed antibodies bind
with the foreign protein to form immune complexes.
These immune complexes may enter the walls of blood
vessels where they set off an inflammatory reaction.
While other types of allergic reactions may produce a rapid response, the serum sickness reaction is
delayed because it takes time for the body to produce
antibodies to the new protein.

Causes and symptoms

ORGANIZATIONS

American Academy of Facial Plastic and Reconstructive
Surgery (AAFPRS). 310 South Henry Street,
Alexandria, VA 22314. (703) 299-9291. <http://
www.facemd.org>.
American Society of Plastic Surgeons (ASPS). 444 East
Algonquin Road, Arlington Heights, IL 60005. (847)
228-9900. <http://www.plasticsurgery.org>.

John T. Lohr, PhD
Rebecca J. Frey, PhD

Septum perforation see Perforated septum
Serenoa repens see Saw palmetto
Serotonin boosters see Selective serotonin
reuptake inhibitors
Serum albumin test see Protein components
test
Serum globulin test see Protein components
test
Serum hepatitis see Hepatitis B
Serum protein electrophoresis see Protein
electrophoresis
GALE ENCYCLOPEDIA OF MEDICINE

The usual symptoms are severe skin reactions,
often on the palms of the hands and soles of the feet.
Fever, sometimes as high as 104o F, is always present
and usually appears before the skin rash.
Joint pain may be reported in up to 50% of cases.
This is usually seen in the larger joints, but occasionally the finger and toe joints may also be involved.
Swelling of lymph nodes, particularly around the
site of the injection, is seen in 10–20% of cases. There
may also be swelling of the head and neck.
Urine analysis may show traces of blood and
protein in the urine.
Other symptoms may involve the heart and central nervous system. These may include changes in
vision, and difficulty in movement. Breathing difficulty may occur.
Traditionally, antitoxins were the most common
cause of serum sickness, but those reports date from a
time when most antitoxins were made from horse
serum. As many as 16% of the people who received
antirabies serum derived from horses developed serum
sickness. The risk of a reaction to antitoxins has
dropped dramatically since manufacturers have
3353

Serum sickness

discoloration. A few patients may have allergic reactions to the anesthetics. The operation in itself, however, is relatively low-risk in that it does not involve
major blood vessels or vital organs. Infection is unlikely if proper surgical technique is observed.

Serum sickness

started using human serum instead of horse serum to
make their products.
Although antitoxins are the most common cause
of serum sickness, a number of drugs have been
reported to cause a serum sickness reaction. The
following list is not complete, but indicates some of
the drugs that have been associated with this type of
reaction:


allopurinol (Zyloprim)



barbiturates



captopril (Capoten)



cephalosporin antibiotics



griseofulvin (Fulvicin, Grifulvin)



penicillins



pehnytoin (Dilantin)



procainamide (Procan SR, Procanbid, Pronestyl-SR)



quinidine (Quinaglute, Quinidex, Quinora)



streptokinase (Streptase, Kabikinase)



sulfonamide antibacterial drugs

Of cases of serum sickness reported to the United
States Food and Drug Administration, the drugs most
commonly associated with the reaction have been the
cephalosporin antibiotics, including cefaclor (Ceclor)
and cefalexin (Keflex) and the sulfonamide combination trimethoprim-sulfamethoxazole (Bactrim,
Septra.) This does not mean that these are high-risk
drugs, since these drugs are very widely used, so that
there are many people exposed to them.
In addition to these substances, allergenic extracts
used for testing and immunization, hormones, and
vaccines have been known to cause serum sickness.

Diagnosis
Diagnosis is made by observing the symptoms and
reviewing the patient’s medical and medication history. Although the symptoms of serum sickness may
be similar to other conditions, patients who present
with symptoms of serum sickness and who have a
recent history of exposure to a drug or other product
which may cause this type of reaction should be
suspected of having serum sickness.

Treatment
The first step in treatment of serum sickness is
always to discontinue the drug or other substance
which is suspected of causing the reaction. After that,
all treatment is symptomatic. Antihistamines, pain
3354

KEY TERMS
Allergy—Altered body reaction, usually hypersensitivity, as a response to exposure to a specific
substance.
Antibody—Any of a large number of proteins that
are produced after stimulation by an antigen and
act specifically against the antigen in an immune
response.
Antihistamine—A drug that inhibits the actions of
histamine. Histamine causes dilatation of capillaries, contraction of smooth muscle, and stimulation of gastric acid secretion.
Antitoxin—An antibody that is capable of neutralizing the specific toxin (a specific cause of disease)
that stimulated its production in the body and is
produced in animals for medical purposes by injection of a toxin or toxoid with the resulting serum
being used to counteract the toxin in other
individuals.
Serum—The clear yellowish fluid that remains
from blood plasma after fibrinogen, prothrombin,
and other clotting factors have been removed by
clot formation—called also blood serum.
Sulfonamide—A sulfa drug, one of a large group of
drugs used to treat bacterial infections.

relievers, and corticosteroids may be given to relieve
the symptoms. The choice of treatment depends on the
severity of the reaction.

Prognosis
Most serum sickness reactions are mild, and disappear on their own after one or two weeks as long as
the cause is removed. Sometimes, symptoms of pain
and discomfort may continue for several weeks, even
after all the observable reactions such as skin rash and
protein in the urine have disappeared. In very rare
cases, however, there can be severe reactions and permanent damage. In very rare but extreme cases, serum
sickness can lead to shock, permanent kidney damage,
and even death.

Prevention
The most effective method of prevention is simple
avoidance of antitoxins that may cause serum sickness. If patients have had a reaction in the past, particularly if the reaction was to a commonly used drug,
GALE ENCYCLOPEDIA OF MEDICINE

severe enough to cause death. SARS is caused by a
virus that is transmitted usually from person to person—predominantly by the aerosolized droplets of
virus infected material.

PERIODICALS

The first known case of SARS was traced to a
November 2002 case in Guangdong province, China.
By mid-February 2003, Chinese health officials
tracked more than 300 cases, including five deaths in
Guangdong province from what was at the time
described as an acute respiratory syndrome. Many
flu-causing viruses have previously originated from
Guangdong province because of cultural and exotic
cuisine practices that bring animals, animal parts, and
humans into close proximity. In such an environment,
pathogens can more easily genetically mutate and
make the leap from animal hosts to humans. The
first cases of SARS showed high rates among
Guangdong food handlers and chefs.

‘‘Children at Rrisk from Medication Mistakes.’’ Houston
Chronicle May 18, 2001.
‘‘Drug allergies.’’ Pediatrics for Parents 18 (2000):1.
Fielding, Jonathan. ‘‘Our Health; Drug Reactions Differ
From Side Effects.’’ The Los Angeles Times
February 7, 2000.
‘‘VA Hospitals Test Smart Cards for Patient Information.’’
Computerworld May 14, 2001.

Chinese health officials initially remained silent
about the outbreak, and no special precautions were
taken to limit travel or prevent the spread of the disease. The world health community, therefore, had no
chance to institute testing, isolation, and quarantine
measures that might have prevented the subsequent
global spread of the disease.

ORGANIZATIONS

On February 21, Liu Jianlun, a 64-year-old
Chinese physician from Zhongshan hospital (later
determined to have been ‘‘super-spreader,’’ a person
capable of infecting unusually high numbers of
contacts) traveled to Hong Kong to attend a family
wedding despite the fact that he had a fever.
Epidemiologists subsequently determined that,
Jianlun passed on the SARS virus to other guests at
the Metropole Hotel where he stayed—including an
American businessman en route to Hanoi, three
women from Singapore, two Canadians, and a Hong
Kong resident. Jianlun’s travel to Hong Kong and the
subsequent travel of those he infected allowed SARS
to spread from China to the infected travelers’
destinations.

When it is necessary to administer an antitoxin,
skin tests may be used to identify people who are at
risk of a reaction. If the situation does not allow
enough time for skin testing, the antitoxin should be
given along with an intravenous antihistamine. Other
drugs, such as epinephrine, which may be needed for
an emergency, should be available.
Resources
BOOKS

1999 Year Book: Allergy and Clinical Immunology. Saint
Louis: Mosby, Inc., 1999.

Action Against Allergy (AAA). PO Box 278, Twickenham
Middlesex, Greater London TW1 4QQ, England.
American Allergy Association (AAA). 3104 E Camelback,
Ste. 459 Phoenix, AZ 85016.

Samuel D. Uretsky, PharmD

Serum therapy see Gammaglobulin

Severe acute respiratory
syndrome (SARS)
Definition
Severe acute respiratory syndrome (SARS) is the
first emergent and highly transmissible viral disease to
appear during the twenty-first century.

Description
Patients with SARS develop flu-like fever, headache, malaise, dry cough and other breathing difficulties. Many patients develop pneumonia, and in 5–10%
of cases, the pneumonia and other complications are
GALE ENCYCLOPEDIA OF MEDICINE

Johnny Chen, the American businessman, grew ill
in Hanoi, Vietnam, and was admitted to a local hospital. Chen infected 20 health care workers at the hospital including noted Italian epidemiologist Carlo
Urbani who worked at the Hanoi World Health
Organization (WHO) office. Urbani provided medical
care for Chen and first formally identified SARS as a
unique disease on February 28, 2003. By early March,
22 hospital workers in Hanoi were ill with SARS.
Unaware of the problems in China, Urbani’s
report drew increased attention among epidemiologists when coupled with news reports in mid-March
3355

Severe acute respiratory syndrome (SARS)

they should be made aware of it, and be advised to
alert physicians and hospitals in the future. Patients
who have had particularly severe reactions may be
advised to wear identification bracelets, or use other
means to alert health care providers.

Severe acute respiratory syndrome (SARS)

that Hong Kong health officials had also discovered
an outbreak of an acute respiratory syndrome among
health care workers. Unsuspecting hospital workers
admitted the Hong Kong man infected by Jianlun to a
general ward at the Prince of Wales Hospital because
it was assumed he had a typical severe pneumonia—a
fairly routine admission. The first notice that clinicians were dealing with an unusual illness came—not
from health notices from China of increasing illnesses
and deaths due to SARS—but from the observation
that hospital staff, along with those subsequently
determined to have been in close proximity to the
infected persons, began to show signs of illness.
Eventually, 138 people, including 34 nurses, 20 doctors, 16 medical students, and 15 other health care
workers, contracted pneumonia.
One of the most intriguing aspects of the early
Hong Kong cases was a cluster of more than 250
SARS cases that occurred in a cluster of high-rise
apartment buildings—many housing health care
workers—that provided evidence of a high rate of
secondary transmission. Epidemiologists conducted
extensive investigations to rule out the hypothesis
that the illnesses were related to some form of local
contamination (e.g., sewage, bacteria on the ventilation system, etc.). Rumors began that the illness was
due to cockroaches or rodents, but no scientific evidence supported the hypothesis that the disease pathogen was carried by insects or animals.
Hong Kong authorities then decided that those
suffering the flu-like symptoms would be given the
option of self-isolation, with family members allowed
to remain confined at home or in special camps.
Compliance checks were conducted by police.
One of the Canadians infected in Hong Kong,
Kwan Sui-Chu, return to Toronto, Ontario, and died
in a Toronto hospital on March 5. As in Hong Kong,
because there were no alert from China about the
SARS outbreak, Canadian officials did not initially
suspect that Sui-Chu had been infected with a highly
contagious virus, until Sui-Chu’s son and five health
care workers showed similar symptoms. By mid-April,
Canada reported more than 130 SARS cases and 15
fatalities.
Increasingly faced with reports that provided evidence of global dissemination, on March 15, 2003, the
World Health Organization (WHO) took the unusual
step of issuing a travel warning that described
SARS is a ‘‘worldwide health threat.’’ WHO officials
announced that SARS cases, and potential cases, had
been tracked from China to Singapore, Thailand,
Vietnam, Indonesia, Philippines, and Canada.
3356

Although the exact cause of the ‘‘acute respiratory
syndrome’’ had not, at that time, been determined,
WHO officials issuance of the precautionary warning
to travelers bound for Southeast Asia about the potential SARS risk served as notice to public health
officials about the potential dangers of SARS.
Within days of the first WHO warning, SARS
cases were reported in United Kingdom, Spain,
Slovenia, Germany, and in the United States.
WHO officials were initially encouraged that isolation procedures and alerts were working to stem the
spread of SARS, as some countries reporting small
numbers of cases experienced no further dissemination to hospital staff or others in contact with SARS
victims. However, in some countries, including
Canada, where SARS cases occurred before WHO
alerts, SARS continued to spread beyond the bounds
of isolated patients.
WHO officials responded by recommending
increased screening and quarantine measures that
included mandatory screening of persons returning
from visits to the most severely affected areas in
China, Southeast Asia, and Hong Kong.
In early April 2003, WHO took the controversial
additional step of recommending against non-essential
travel to Hong Kong and the Guangdong province of
China. The recommendation, sought by infectious
disease specialists, was not controversial within the
medical community, but caused immediate concern
regarding the potentially widespread economic impacts.
Mounting reports of SARS showed a increasing
global dissemination of the virus. By April 9, the first
confirmed reports of SARS cases in Africa reached
WHO headquarters, and eight days later, a confirmed
case was discovered in India.

Causes and symptoms
In mid-April 2003, Canadian scientists at the
British Columbia Cancer Agency in Vancouver
announced that they that sequenced the genome of
the coronavirus most likely to be the cause of SARS.
Within days, scientists at the Centers for Disease
Control (CDC) in Atlanta, Georgia, offered a genomic
map that confirmed more than 99% of the Canadian
findings.
Both genetic maps were generated from studies of
viruses isolated from SARS cases. The particular coronavirus mapped had a genomic sequence of 29,727
nucleotides—average for the family of coronavirus
that typically contain between 29,000-31,000
nucleotides.
GALE ENCYCLOPEDIA OF MEDICINE

Identification of a specific pathogen can be a complex process, and positive identification requires thousands of tests. All testing is conducted with regard to
testing Koch’s postulates—the four conditions that
must be met for an organism to be determined to the
cause of a disease. First, the organism must be present
in every case of the disease. Second, the organism must
be able to be isolated from the host and grown in
laboratory conditions. Third, the disease must be
reproduced when the isolated organism is introduced
into another, healthy host. The fourth postulate
stipulates that the same organism must be able to be
recovered and purified from the host that was experimentally infected.
Early data indicates that SARS has an incubation
period range of two to 10 days, with an average incubation of about four days. Much of the inoculation
period allows the virus to be both transported and
spread by an asymptomatic carrier. With air travel,
asymptotic carriers can travel to anywhere in the
world. The initial symptoms are non-specific and common to the flu. Infected cases then typically spike a
high fever 100.48F (388C) as they develop a cough,
shortness of breath, and difficulty breathing. SARS
often fulminates (reaches it maximum progression) in
a severe pneumonia that can cause respiratory failure
and death in about 10% of its victims.

Diagnosis
Currently, initial tests include blood cultures,
Gram stain, chest radiograph, and tests for other
viral respiratory pathogens such as influenza A and
B. Other serologic techniques are used, and if SARS is
suspected, samples are forwarded to state/local public
health departments and/or the CDC for coronavirus
antibody testing.

Treatment
As of May 1, 2003, no therapy was demonstrated
to have clinical effectiveness against the virus that
GALE ENCYCLOPEDIA OF MEDICINE

causes SARS, and physicians could offer only supportive therapy (e.g. administration of fluids, oxygen,
ventilation, etc.).

Prognosis
By late April/early May 2003, WHO officials had
confirmed reports of more than 3,000 cases of SARS
from 18 different countries with 111 deaths attributed
to the disease (about a 5–10% death rate). United
States health officials reported 193 cases with no
deaths. Significantly, all but 20 of the U.S. cases were
linked to travel to infected areas, and the other 20
cases were accounted for by secondary transmission
from infected patients to family members and health
care workers.
Information on countries reporting SARS and the
cumulative total of cases and deaths is updated each
day on the WHO SARS web site at <http;//
www.who.int/csr/sarscountry/en/>.

Prevention
Until a vaccine is developed, isolation and quarantine remain potent tools in the modern public health
arsenal. Both procedures seek to control exposure to
infected individuals or materials. Isolation procedures
are used with patients with a confirmed illness.
Quarantine rules and procedures apply to individuals
who are not currently ill, but are known to have been
exposed to the illness (e.g., been in the company of a
infected person or come in contact with infected
materials).
Isolation and quarantine both act to restrict
movement and to slow or stop the spread of disease
within a community. Depending on the illness,
patients placed in isolation may be cared for in hospitals, specialized health care facilities, or in less severe
cases, at home. Isolation is a standard procedure for
TB patients. In most cases, isolation is voluntary;
however, isolation can be compelled by federal, state,
and some local law.
States governments within the United States have
a general authority to set and enforce quarantine conditions. At the federal level, the Centers for Disease
Control and Prevention’s (CDC) Division of Global
Migration and Quarantine is empowered to detain,
examine, or conditionally release (release with restrictions on movement or with a required treatment protocol) individuals suspected of carrying certain listed
communicable diseases.
As of April 27, 2003, the CDC in Atlanta recommended SARS patients be voluntarily isolated, but
3357

Severe acute respiratory syndrome (SARS)

Proof that the coronavirus mapped was the specific virus responsible for SARS would eventually come
from animal testing. Rhesus monkeys were exposed to
the virus via injection and inhalation and then monitored to determine whether SARS like symptoms
developed, and then if sick animals exhibited a histological pathology (i.e., an examination of the tissue and
cellular level pathology) similar to findings in human
patients. Other tests, including polymerase chain reaction (PCR) testing helped positively match the specific
coronavirus present in the lung tissue, blood, and feces
of infected animals to the exposure virus.

Severe combined immunodeficiency

had not recommended enforced isolation or quarantine. Regardless, CDC and other public heath officials, including the Surgeon General, sought and
secured increased powers to deal with SARS. On
April 4, 2003, U.S. President George W. Bush signed
Presidential Executive Order 13295 that added SARS
to a list of quarantinable communicable diseases.
The order provided health officials with the broader
powers to seek ‘‘...apprehension, detention, or conditional release of individuals to prevent the introduction, transmission, or spread of suspected
communicable diseases...’’
Travel advisories issued by WHO should be
reviewed and people who must travel to areas with
SARS outbreaks should follow such preventative
measures as frequent hand washing and avoidance of
large crowds. Likewise, family members caring for
suspected and/or confirmed SARS patients should
wash hands frequently, avoid direct contact with the
patient’s bodily fluids, and monitor their own possible
development of symptoms closely.
Brenda Wilmoth Lerner
K. Lee Lerner

Severe combined
immunodeficiency
Definition
Severe combined immunodeficiency (SCID) is the
most serious human immunodeficiency disorder(s). It
is a group of congenital disorders in which both the
humoral part of the patient’s immune system and the
cells involved in immune responses fail to work properly. Children with SCID are vulnerable to recurrent
severe infections, retarded growth, and early death.

Description
SCID is thought to affect between one in every
100,000 persons, and one in every 500,000 infants.
Several different immune system disorders are currently grouped under SCID:


Swiss-type agammaglobulinemia. This was the first
type of SCID discovered, in Switzerland in the
1950s.



Adenosine deaminase deficiency (ADA). About
50% of SCID cases are of this type. ADA deficiency

3358

leads to low levels of B and T cells in the child’s
immune system.


Autosomal recessive. About 40% of SCID cases are
inherited from the parents in an autosomal recessive
pattern.



Bare lymphocyte syndrome. In this form of SCID,
the white blood cells (lymphocytes) in the baby’s
blood are missing certain proteins. Without these
proteins, the lymphocytes cannot activate the
T cells in the immune system.



SCID with leukopenia. Children with this form of
SCID are lacking a type of white blood cell called a
granulocyte.

In order to understand why SCID is considered
the most severe immunodeficiency disorder, it is helpful to have an outline of the parts of the human
immune system. It has three parts: cellular, humoral,
and nonspecific. The cellular and humoral parts of
the system are both needed to fight infections–
they recognize disease agents and attack them. The
cellular system is composed of many classes of
T-lymphocytes (white blood cells that detect foreign
invaders called antigens). The humoral system is
made up of B cells, which are the only cells in the
body that make antibodies. In SCID, neither the
cellular nor the humoral part of the immune system
is working properly.

Causes and symptoms
SCID is an inherited disorder. There are two ways
in which a developing fetus’ immune system can fail to
develop normally. In the first type of genetic problem,
both B and T cells are defective. In the second type,
only the T cells are abnormal, but their defect affects
the functioning of the B cells.
For the first few months of life, a child with SCID
is protected by antibodies in the mother’s blood. As
early as three months of age, however, the SCID child
begins to suffer from mouth infections (thrush),
chronic diarrhea, otitis media and pulmonary infections, including pneumocystis pneumonia. The child
loses weight, becomes very weak, and eventually dies
from an opportunistic infection.

Diagnosis
SCID is diagnosed by the typing of T and B cells in
the child’s blood. B cells can be detected by immunofluorescence tests for surface markers (unique proteins)on the cells. T cells can be identified in tissue sections
(samples) using enzyme-labeled antibodies.
GALE ENCYCLOPEDIA OF MEDICINE

Adenosine deaminase (ADA)—An enzyme that is
lacking in a specific type of SCID. Children with an
ADA deficiency have low levels of both B and T
cells.
Antigens—A substance that usually causes the formation of an antibody. A foreign invaders in the
body.
Autosomal recessive inheritance—A pattern of
inheritance of a recessive gene where, among
other things, both parents may not show symptoms.
B cell—A type of lymphocyte or white blood cell
that is derived from precursor cells in the bone
marrow.
Congenital—Present at the time of birth. Most
forms of SCID are hereditary as well as congenital.
Gene therapy—An experimental treatment for
SCID that consists of implanting a gene for ADA
into an activated virus and merging it with some of
the patient’s own T cells. The corrected T cells are
infused back into the patient every few months.
Humoral—Pertaining to or derived from a body
fluid. The humoral part of the immune system
includes antibodies and immunoglobulins in
blood serum.
Lymphocyte—A type of white blood cell that is
important in the formation of antibodies.
Orphan drug—A drug that is known to be useful in
treatment but lacks sufficient funding for further
research and development.
PEG-ADA—An orphan drug that is useful in treating SCID related to ADA deficiency.
T cells—Lymphocytes that originate in the thymus
gland. T cells regulate the immune system’s
response to infections. The thymus gland is small
or underdeveloped in children with SCID.
Thrush—A disease of the mouth caused by a yeast,
Candida albicans.

In 1990, the Food and Drug Administration
(FDA) approved PEG-ADA, an orphan drug (not
available in US but available elsewhere), for the treatment of SCID. PEG-ADA, which is also called
pegademase bovine, works by replacing the ADA
deficiency in children with this form of SCID.
Children who receive weekly injections of PEG-ADA
appear to have normal immune functions restored.
Another treatment that is still in the experimental
stage is gene therapy. In gene therapy, the children
receive periodic infusions of their own T cells corrected with a gene for ADA that has been implanted
in an activated virus.

Prognosis
Currently, there is no cure for SCID. Most
untreated patients die before age two.

Prevention
Genetic counseling is recommended for parents of
a child with SCID.
Resources
ORGANIZATIONS

Immune Deficiency Foundation. 25 W. Chesapeake Ave.,
Suite 206, Towson, MD 21204. (800) 296-4433.
<http://www.primaryimmune.org>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Rebecca J. Frey, PhD

Sex hormones tests
Definition
Sex hormones tests measure levels of the sex hormones, including estrogen, progesterone, and
testosterone.

Treatment
Patients with SCID can be treated with antibiotics and immune serum to protect them from infections, but these treatments cannot cure the disorder.
Bone marrow transplants are currently regarded
as one of the few effective standard treatments for
SCID.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
The sex hormone tests are ordered to determine if
secretion of these hormones is normal. Estrogen fraction test is done to evaluate sexual maturity, menstrual
problems, and fertility problems in females. This test
may also be used to test for tumors that excrete
3359

Sex hormones tests

Investigational treatments

KEY TERMS

Sex hormones tests

estrogen. In pregnant women it aids in determining
fetal-placental health. Estrogen fraction is also used to
evaluate males who have enlargement of one or both
breasts (gynecomastia), or who have feminization syndromes, where they display female sex characteristics.

pregnancy suggest fetoplacental deterioration and
require prompt reassessment of the pregnancy, including the possibility of early delivery.

Progesterone assay test is ordered to evaluate
women who are having difficulty becoming pregnant
or maintaining a pregnancy, and to monitor high-risk
pregnancies.

Progesterone is essential for the healthy functioning of the female reproductive system. Produced in the
ovaries during the second half of the menstrual cycle,
and by the placenta during pregnancy, small amounts
of progesterone are also produced in the adrenal
glands and testes.

Testosterone levels are ordered to evaluate:


ambiguous sex characteristics



precocious puberty



virilizing syndromes in the female



infertility in the male



rare tumors of the ovary and testicle

Description
The sex hormones control the development of
primary and secondary sexual characteristics. They
regulate the sex-related functions of the body, such
as the menstrual cycle or the production of eggs or
sperm. There are three main types of sex hormones:


the female sex hormones (called the estrogen
hormones)



the progesterone hormones (which help the body
prepare for and maintain pregnancy)



the male sex hormones, or the androgen hormones

Female sex hormones are responsible for normal
menstruation and the development of secondary
female characteristics. Testosterone is a hormone
that induces puberty in the male and maintains male
secondary sex characteristics. In females, the adrenal
glands and the ovaries secrete small amounts of
testosterone.
Estrogen
Estrogen is tested to evaluate menstrual status,
sexual maturity, and gynecomastia (or feminization
syndromes). It is a tumor marker for patients with
certain ovarian tumors. E1, a type of estrogen, is the
most active estrogen in the nonpregnant female.
E3 (estriol) is the major estrogen in the pregnant
female. It is produced in the placenta. Excretion of
estriol increases around the eighth week of gestation
and continues to rise until shortly before delivery.
Serial urine and blood studies of this hormone are
used to assess placental function and fetal normality
in high-risk pregnancies. Falling values during
3360

Progesterone

After ovulation, an increase of progesterone
causes the uterine lining to thicken in preparation for
the implantation of a fertilized egg. If this event does
not take place, progesterone and estrogen levels fall,
resulting in shedding of the uterine lining.
Progesterone is essential during pregnancy, not
only ensuring normal functioning of the placenta,
but passing into the developing baby’s circulation,
where it is converted in the adrenal glands to corticosteroid hormones.
Testosterone
Testosterone is the most important of the male sex
hormones. It is responsible for stimulating bone and
muscle growth, and sexual development. It is produced by the testes and in very small amounts by the
ovaries. Most testosterone tests measure total
testosterone.
Testosterone stimulates sperm production (spermatogenesis), and influences the development of male
secondary sex characteristics. Overproduction of testosterone caused by testicular, adrenal, or pituitary
tumors in the young male may result in precocious
puberty.
Overproduction of testosterone in females, caused
by ovarian and adrenal tumors, can result in masculinization, the symptoms of which include cessation of
the menstrual cycle (amenorrhea) and excessive
growth of body hair (hirsutism).
When reduced levels of testosterone in the male
indicate underactivity of the testes (hypogonadism),
testosterone stimulation tests may be ordered.

Preparation
The progesterone and testosterone tests require a
blood sample; it is not necessary for the patient to
restrict food or fluids before the test. Testosterone
specimens should be drawn in the morning, as testosterone levels are highest in the early morning hours.
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Risks for these blood tests are minimal, but may
include slight bleeding from the puncture site, fainting
or feeling lightheaded after having blood drawn, or
blood accumulating under the puncture site
(hematoma).

Normal results
Estrogen levels vary in women, ranging from 24–
149 picograms per ml of blood. In men, the normal
range is between 12–34 picograms per ml of blood.
Progesterone levels vary from less than 150 nanograms per deciliter (ng/dL) of blood to 2,000 nanograms in menstruating women. During pregnancy,
progesterone levels range from 1,500–20,000 ng/dL
of blood.
Testosterone values vary from laboratory to
laboratory, but can generally be found within the
following levels:


Men. 300–1,200 ng/dL



Women. 30–95 ng/dL



Prepubertal children. Less than 100 ng/dL (boys),
less than 40 ng/dL (girls).

Abnormal results
Increased levels of estrogen are seen in feminization syndromes:


when a male begins to develop female secondary sex
characteristics



during precocious puberty



when children develop secondary sexual characteristics at an abnormally early age



because of ovarian, testicular, or adrenal tumor



During normal pregnancy, cirrhosis, and increased
thyroid levels (hyperthyroidism)

Decreased levels of estrogen are found in the following conditions:


a failing pregnancy



during menopause



anorexia nervosa

GALE ENCYCLOPEDIA OF MEDICINE



primary and secondary hypogonadism



turner’s syndrome, seen in females with one missing
X chromosome
Increased levels of progesterone are seen:



during ovulation and pregnancy



with certain types of ovarian cysts



with a tumor of
choriocarcinoma

the

ovary

known

as

a

Decreased levels of progesterone are seen:


in toxemia of pregnancy



with a threatened abortion



during placental failure



after fetal death



with amenorrhea



due to ovarian dysfunction
Increased levels (male) of testosterone are found

in:


sexual precocity



the viral infection of encephalitis



tumors involving the adrenal glands



testicular tumors



excessive thyroid production (hyperthyroidism)



testosterone resistance syndromes.
Decreased levels (male) of testosterone are seen in:



Klinefelter syndrome



a chromosomal deficiency



primary and secondary hypogonadism



down syndrome



surgical removal of the testicles



cirrhosis.

Increased levels (females) of testosterone are
found in ovarian and adrenal tumors and in the presence of excessive hair growth of unknown cause
(hirsutism).
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Sex reassignment surgery see Gender reassignment surgery
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Sex hormones tests

The estrogen fraction test can be performed on blood
and/or urine. It is not necessary for the patient to
restrict food or fluids for either test. If a 24-hour
urine test has been requested, the patient should call
the laboratory for instructions.

Sexual dysfunction



Sex therapy
Definition
Sex therapy is the treatment of sexual dysfunction.

Aftercare

Purpose
Sex therapy utilizes various techniques in order to
relieve sexual dysfunction commonly caused by premature ejaculation or sexual anxiety and to improve
the sexual health of the patient.

Precautions
Sexual dysfunction conjures up feelings of guilt,
anger, insecurity, frustration, and rejection. Therapy
is slow and requires open communication and understanding between sexual partners. Therapy may inadvertently address interpersonal communication
problems.

Description

Squeeze technique, which is used to treat premature
ejaculation. When the man feels the urge to ejaculate,
his partner squeezes his penis just below the head.
This stops ejaculation and gives the man more control over his response.

Habits change slowly. All the techniques must be
practiced faithfully for long periods of time to relearn
behaviors. Communication is imperative.
Resources
BOOKS

Masters, William H., Virginia E. Johnson, and Robert C.
Kolodny. Heterosexuality. New York: Harper Collins
Publishers, Inc., 1994.

J. Ricker Polsdorfer, MD

Sexual abuse see Rape and sexual assault
Sexual arousal disorders see Sexual
dysfunction

Sex therapy is conducted by a trained therapist,
doctor, or psychologist. The initial sessions should
cover a complete history not only of the sexual problem but of the entire relationship and each individual’s background and personality. The sexual
relationship should be discussed in the context of the
entire relationship. In fact, sexual counseling may deemphasize sex until other aspects of the relationship
are better understood and communicated.

Sexual desire disorders see Sexual
dysfunction

There are several techniques that combat sexual
dysfunction and are used in sex therapy. They include:

Sexual dysfunction is broadly defined as the
inability to fully enjoy sexual intercourse.
Specifically, sexual dysfunctions are disorders that
interfere with a full sexual response cycle. These disorders make it difficult for a person to enjoy or to have
sexual intercourse. While sexual dysfunction rarely
threatens physical health, it can take a heavy psychological toll, bringing on depression, anxiety, and debilitating feelings of inadequacy.





Semans’ technique:which is used to help combat premature ejaculation with a ‘‘start-stop’’ approach to
penis stimulation. By stimulating the man up to the
point of ejaculation and then stopping, the man will
become more aware of his response. More awareness
leads to greater control, and open stimulation of
both partners leads to greater communication and
less anxiety. The start-stop technique is conducted
four times until the man is allowed to ejaculate.
Sensate focus therapy, the practice of nongenital and
genital touching between partners in order to
decrease sexual anxiety and build communication.
First, partners explore each other’s bodies without
touching the genitals or breasts. Once the couple is
comfortable with nongenital touching, they can
expand to genital stimulation. Intercourse is prohibited in order to allow the partners to expand their
intimacy and communication.

3362

Sexual dysfunction
Definition

Description
Sexual dysfunction takes different forms in men
and women. A dysfunction can be life-long and always
present, acquired, situational, or generalized, occurring despite the situation. A man may have a sexual
problem if he:


ejaculates before he or his partner desires



does not ejaculate,
ejaculation

or

experiences

delayed

GALE ENCYCLOPEDIA OF MEDICINE

is unable to have an erection sufficient for pleasurable intercourse



feels pain during intercourse



lacks or loses sexual desire
A woman may have a sexual problem if she:



lacks or loses sexual desire



has difficulty achieving orgasm



feels anxiety during intercourse



feels pain during intercourse



feels vaginal or other muscles contract involuntarily
before or during sex



has inadequate lubrication

The most common sexual dysfunctions in men
include:


Erectile dysfunction: an impairment of the erectile
reflex. The man is unable to have or maintain an
erection that is firm enough for coitus or intercourse.



Premature ejaculation: rapid ejaculation with minimal sexual stimulation before, on, or shortly after
penetration and before the person wishes it.



Ejaculatory incompetence: the inability to ejaculate
within the vagina despite a firm erection and relatively high levels of sexual arousal.



Retarded ejaculation: a condition in which the bladder neck does not close off properly during orgasm
so that the semen spurts backward into the bladder.

Until recently, it was presumed that women were
less sexual than men. In the past two decades, traditional views of female sexuality were all but demolished, and women’s sexual needs became accepted as
legitimate in their own right.
Female sexual dysfunctions include:




Sexual arousal disorder: the inhibition of the general
arousal aspect of sexual response. A woman with this
disorder does not lubricate, her vagina does not
swell, and the muscle that surrounds the outer third
of the vagina does not tighten—a series of changes
that normally prepare the body for orgasm (‘‘the
orgasmic platform’’). Also, in this disorder, the
woman typically does not feel erotic sensations.
Orgasmic disorder: the impairment of the orgasmic
component of the female sexual response. The
woman may be sexually aroused but never reach
orgasm. Orgasmic capacity is less than would be
reasonable for her age, sexual experience, and the
adequacy of sexual stimulation she receives.

GALE ENCYCLOPEDIA OF MEDICINE



Vaginismus: a condition in which the muscles around
the outer third of the vagina have involuntary spasms
in response to attempts at vaginal penetration.



Painful intercourse: a condition that can occur at any
age. Pain can appear at the start of intercourse, midway through coital activities, at the time of orgasm,
or after intercourse is completed. The pain can be felt
as burning, sharp searing, or cramping; it can be
external, within the vagina, or deep in the pelvic
region or abdomen.

Causes and symptoms
Many factors, of both physical and psychological
natures, can affect sexual response and performance.
Injuries, ailments, and drugs are among the physical
influences; in addition, there is increasing evidence
that chemicals and other environmental pollutants
depress sexual function. As for psychological factors,
sexual dysfunction may have roots in traumatic events
such as rape or incest, guilt feelings, a poor self-image,
depression, chronic fatigue, certain religious beliefs, or
marital problems. Dysfunction is often associated
with anxiety. If a man operates under the misconception that all sexual activity must lead to intercourse
and to orgasm by his partner, and if the expectation is
not met, he may consider the act a failure.
Men
With premature ejaculation, physical causes are
rare, although the problem is sometimes linked to a
neurological disorder, prostate infection, or urethritis.
Possible psychological causes include anxiety (mainly
performance anxiety), guilt feelings about sex, and
ambivalence toward women. However, research has
failed to show a direct link between premature ejaculation and anxiety. Rather, premature ejaculation
seems more related to sexual inexperience in learning
to modulate arousal.
When men experience painful intercourse, the
cause is usually physical; an infection of the prostate,
urethra, or testes, or an allergic reaction to spermicide
or condoms. Painful erections may be caused by
Peyronie’s disease, fibrous plaques on the upper side
of the penis that often produce a bend during erection.
Cancer of the penis or testes and arthritis of the lower
back can also cause pain.
Retrograde ejaculation occurs in men who have
had prostate or urethral surgery, take medication that
keeps the bladder open, or suffer from diabetes, a
disease that can injure the nerves that normally close
the bladder during ejaculation.
3363

Sexual dysfunction



Sexual dysfunction

Erectile dysfunction is more likely than other dysfunctions to have a physical cause. Drugs, diabetes
(the most common physical cause), Parkinson’s disease, multiple sclerosis, and spinal cord lesions can all
be causes of erectile dysfunction. When physical
causes are ruled out, anxiety is the most likely psychological cause of erectile dysfunction.
Women
Dysfunctions of arousal and orgasm in women also
may be physical or psychological in origin. Among the
most common causes are day-to-day discord with one’s
partner and inadequate stimulation by the partner.
Finally, sexual desire can wane as one ages, although
this varies greatly from person to person.
Pain during intercourse can occur for any number
of reasons, and location is sometimes a clue to the
cause. Pain in the vaginal area may be due to infection,
such as urethritis; also, vaginal tissues may become
thinner and more sensitive during breast-feeding and
after menopause. Deeper pain may have a pelvic
source, such as endometriosis, pelvic adhesions, or uterine abnormalities. Pain can also have a psychological
cause, such as fear of injury, guilt feelings about sex,
fear of pregnancy or injury to the fetus during pregnancy, or recollection of a previous painful experience.
Vaginismus may be provoked by these psychological causes as well, or it may begin as a response to
pain, and continue after the pain is gone. Both partners should understand that the vaginal contraction is
an involuntary response, outside the woman’s control.
Similarly, insufficient lubrication is involuntary,
and may be part of a complex cycle. Low sexual
response may lead to inadequate lubrication, which
may lead to discomfort, and so on.

Diagnosis
In deciding when a sexual dysfunction is present,
it is necessary to remember that while some people
may be interested in sex at almost any time, others
have low or seemingly nonexistent levels of sexual
interest. Only when it is a source of personal or relationship distress, instead of voluntary choice, is it
classified as a sexual dysfunction.
The first step in diagnosing a sexual dysfunction is
usually discussing the problem with a doctor, who will
need to ask further questions in an attempt to differentiate among the types of sexual dysfunction. The
physician may also perform a physical exam of the
genitals, and may order further medical tests, including measurement of hormone levels in the blood. Men
3364

may be referred to a specialist in diseases of the urinary
and genital organs (urologist), and primary care physicians may refer women to a gynecologist.

Treatment
Treatments break down into two main kinds:
behavioral psychotherapy and physical. Sex therapy,
which is ideally provided by a member of the
American Association of Sexual Educators,
Counselors, and Therapists (AASECT), universally
emphasizes correcting sexual misinformation, the
importance of improved partner communication and
honesty, anxiety reduction, sensual experience and
pleasure, and interpersonal tolerance and acceptance.
Sex therapists believe that many sexual disorders are
rooted in learned patterns and values. These are
termed psychogenic. An underlying assumption of
sex therapy is that relatively short-term outpatient
therapy can alleviate learned patterns, restrict symptoms, and allow a greater satisfaction with sexual
experiences.
In some cases, a specific technique may be used
during intercourse to correct a dysfunction. One of the
most common is the ‘‘squeeze technique’’ to prevent
premature ejaculation. When a man feels that an
orgasm is imminent, he withdraws from his partner.
Then, the man or his partner gently squeezes the head
of the penis to halt the orgasm. After 20–30 seconds,
the couple may resume intercourse. The couple may
do this several times before the man proceeds to
ejaculation.
In cases where significant sexual dysfunction is
linked to a broader emotional problem, such as
depression or substance abuse, intensive psychotherapy and/or pharmaceutical intervention may be
appropriate.
In many cases, doctors may prescribe medications
to treat an underlying physical cause or sexual dysfunction. Possible medical treatments include:


clomipramine
ejaculation

and

fluoxetine



papaverine and prostaglandin for erectile difficulties



hormone replacement
dysfunctions



Viagra, a pill approved in 1998 as a treatment for
impotence

therapy

for

premature

for

female

Alternative treatment
A variety of alternative therapies can be useful in
the treatment of sexual dysfunction. Counseling or
GALE ENCYCLOPEDIA OF MEDICINE

Ejaculatory incompetence—The inability to ejaculate within the vagina.
Erectile dysfunction—Difficulty achieving or
maintaining an erect penis.

with premature ejaculation can be successfully treated
in two to three months. Furthermore, the gains made
in sex therapy tend to be long-lasting rather than
short-lived.
Resources
ORGANIZATIONS

Orgasmic disorder—The impairment of the ability
to reach sexual climax.
Painful intercourse (dyspareunia)—Generally
thought of as a female dysfunction but also affects
males. Pain can occur anywhere.

American Academy of Clinical Sexologists. 1929 18th St.
NW, Suite 1166, Washington, DC 20009. (202)
462-2122.
American Association for Marriage and Family Therapy.
1133 15th St., NW Suite 300, Washington, DC 200052710. (202) 452-0109. <http://www.aamft.org>.

Premature ejaculation—Rapid ejaculation before
the person wishes it, usually in less than one to two
minutes after beginning intercourse.

David James Doermann

Retrograde ejaculation—A condition in which the
semen spurts backward into the bladder.
Sexual arousal disorder—The inhibition of the general arousal aspect of sexual response.
Vaginismus—Muscles around the outer third of the
vagina have involuntary spasms in response to
attempts at vaginal penetration, not allowing for
penetration.

psychotherapy is highly recommended to address any
emotional or mental components of the disorder.
Botanical medicine, either western, Chinese, or ayurvedic, as well as nutritional supplementation, can help
resolve biochemical causes of sexual dysfunction.
Acupuncture and homeopathic treatment can be helpful by focusing on the energetic aspects of the disorder.
Some problems with sexual function are normal.
For example, women starting a new or first relationship may feel sore or bruised after intercourse and find
that an over-the-counter lubricant makes sex more
pleasurable. Simple techniques, such as soaking in a
warm bath, may relax a person before intercourse and
improve the experience. Yoga and meditation provide
needed mental and physical relaxation for several conditions, such as vaginismus. Relaxation therapy eases
and relieves anxiety about dysfunction. Massage is
extremely effective at reducing stress, especially if performed by the partner.

Prognosis
There is no single cure for sexual dysfunctions, but
almost all can be controlled. Most people who have a
sexual dysfunction fare well once they get into a treatment program. For example, a high percentage of men
GALE ENCYCLOPEDIA OF MEDICINE

Sexual perversions
Definition
Sexual perversions are conditions in which sexual
excitement or orgasm is associated with acts or imagery that are considered unusual within the culture. To
avoid problems associated with the stigmatization of
labels, the neutral term paraphilia, derived from
Greek roots meaning ‘‘alongside of’’ and ‘‘love,’’ is
used to describe what used to be called sexual perversions. A paraphilia is a condition in which a person’s
sexual arousal and gratification depend on a fantasy
theme of an unusual situation or object that becomes
the principal focus of sexual behavior.

Description
Paraphilias can revolve around a particular sexual
object or a particular act. They are defined by DSMIV as ‘‘sexual impulse disorders characterized by
intensely arousing, recurrent sexual fantasies, urges
and behaviors considered deviant with respect to cultural norms and that produce clinically significant
distress or impairment in social, occupational or
other important areas of psychosocial functioning.’’
The nature of a paraphilia is generally specific and
unchanging, and most of the paraphilias are far more
common in men than in women.
Paraphilias differ from what some people might
consider ‘‘normal’’ sexual activity in that these behaviors cause significant distress or impairment in areas
of life functioning. They do not refer to the normal
use of sexual fantasy, activity, or objects to heighten
sexual excitement where there is no distress or
3365

Sexual perversions

KEY TERMS

Sexual perversions

impairment. The most common signs of sexual activity
that can be classified as paraphilia include: the inability to resist an impulse for the sexual act, the
requirement of participation by non-consenting or
under-aged individuals, legal consequences, resulting
sexual dysfunction, and interference with normal
social relationships.
Paraphilias include fantasies, behaviors, and/or
urges which:


involve nonhuman sexual objects, such as shoes or
undergarments



require the suffering or humiliation of oneself or
partner



involve children or other non-consenting partners
The most common paraphilias are:



exhibitionism, or exposure of the genitals



fetishism, or the use of nonliving objects



frotteurism, or touching and rubbing against a nonconsenting person



pedophilia, or the focus on prepubescent children



sexual masochism, or the receiving of humiliation or
suffering



sexual sadism, or the inflicting of humiliation or
suffering



transvestic fetishism, or cross-dressing



voyeurism, or watching others engage in undressing
or sexual activity

A paraphiliac often has more than one paraphilia.
Paraphilias often result in a variety of associated problems, such as guilt, depression, shame, isolation, and
impairment in the capacity for normal social and sexual relationships. A paraphilia can, and often does,
become highly idiosyncratic and ritualized.

Causes and symptoms
There is very little certainty about what causes a
paraphilia. Psychoanalysts generally theorize that
these conditions represent a regression to or a fixation
at an earlier level of psychosexual development resulting in a repetitive pattern of sexual behavior that is not
mature in its application and expression. In other
words, an individual repeats or reverts to a sexual
habit arising early in life. Another psychoanalytic theory holds that these conditions are all expressions of
hostility in which sexual fantasies or unusual sexual
acts become a means of obtaining revenge for a childhood trauma. The persistent, repetitive nature of the
paraphilia is caused by an inability to erase the
3366

underlying trauma completely. Indeed, a history of
childhood sexual abuse is sometimes seen in individuals with paraphilias.
However, behaviorists suggest, instead, that the
paraphilia begins via a process of conditioning.
Nonsexual objects can become sexually arousing if
they are frequently and repeatedly associated with a
pleasurable sexual activity. The development of a
paraphilia is not usually a matter of conditioning
alone; there must usually be some predisposing factor,
such as difficulty forming person-to-person sexual
relationships or poor self-esteem.
The following are situations or causes that might
lead someone in a paraphiliac direction:


parents who humiliate and punish a small boy for
strutting around with an erect penis



a young boy who is sexually abused



an individual who is dressed in a woman’s clothes as
a form of parental punishment



fear of sexual performance or intimacy



inadequate counseling



excessive alcohol intake



physiological problems



sociocultural factors



psychosexual trauma

Diagnosis
Whatever the cause, paraphiliacs apparently
rarely seek treatment unless they are induced into it
by an arrest or discovery by a family member. This
makes diagnosis before a confrontation very difficult.
Paraphiliacs may select an occupation, or develop
a hobby or volunteer work, that puts them in contact
with the desired erotic stimuli, for example, selling
women’s shoes or lingerie in fetishism, or working
with children in pedophilia. Other coexistent problems
may be alcohol or drug abuse, intimacy problems, and
personality disturbances, especially emotional immaturity. Additionally, there may be sexual dysfunctions.
Erectile dysfunction and an inability to ejaculate may
be common in attempts at sexual activity without the
paraphiliac theme.
Paraphilias may be mild, moderate, or severe. An
individual with mild paraphilia is markedly distressed
by the recurrent paraphiliac urges but has never acted
on them. The moderate has occasionally acted on the
paraphilic urge. A severe paraphiliac has repeatedly
acted on the urge.
GALE ENCYCLOPEDIA OF MEDICINE

The literature describing treatment is fragmentary
and incomplete. Traditional psychoanalysis has not
been particularly effective with paraphilia and generally requires several years of treatment. Therapy with
hypnosis has also had poor results. Current interests
focus primarily on several behavioral techniques that
include the following:




Aversion imagery involves the pairing of a sexually
arousing paraphilic stimulus with an unpleasant
image, such as being arrested or having one’s name
appear in the newspaper.
Desensitization procedures neutralize the anxietyprovoking aspects of nonparaphilic sexual situations and behavior by a process of gradual exposure.
For example, a man afraid of having sexual contact
with women his own age might be led through a
series of relaxation procedures aimed at reducing
his anxiety.



Social skills training is used with either of the other
approaches and is aimed at improving a person’s
ability to form interpersonal relationships.



Orgasmic reconditioning may instruct a person to
masturbate using his paraphilia fantasy and to
switch to a more appropriate fantasy just at the
moment of orgasm.

In addition to these therapies, drugs are sometimes prescribed to treat paraphilic behaviors. Drugs
that drastically lower testosterone temporarily (antiandrogens) have been used for the control of repetitive
deviant sexual behaviors and have been prescribed for
paraphilia-related disorders as well. Cyproterone acetate inhibits testosterone directly at androgen receptor
sites. In its oral form, the usual prescribed dosage
range is 50–200 mg per day.
Serotonergics (drugs that boost levels of the brain
chemical serotonin) are prescribed for anxious and
depressive symptoms. Of the serotonergic agents
reported, fluoxetine has received the most attention,
although lithium, clomipramine, buspirone, and sertraline are reported as effective in case reports and
open clinical trials with outpatients. Other alternative
augmentation strategies that may be effective include
adding a low dose of a secondary amine tricyclic antidepressant to the primary serotonergics, but these
reports are only anecdotal.

Prognosis
Despite more than a decade of experience with
psychotherapeutic treatment programs, most workers
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Exhibitionism—Obtaining sexual arousal by
exposing genitals to an unsuspecting stranger.
Fetishism—Obtaining sexual arousal using or
thinking about an inanimate object or part of the
body.
Frotteurism—Obtaining sexual arousal and gratification by rubbing one’s genitals against others in
public places.
Masochism—Sexual arousal by having pain and/or
humiliation inflicted upon oneself.
Pedophilia—Sex or sexual activity with children
who have not reached puberty.
Sadism—Sexual arousal through inflicting pain on
another person.
Transvestitism—Sexual arousal from dressing in
the clothes of the opposite sex.
Voyeurism—Sexual arousal by observing nude
individuals without their knowledge.

in the field are not convinced that they have a high
degree of success. Furthermore, because some cases
involve severe abuse, many in the general public would
prefer to ‘‘lock up’’ the sex offender than to have him
out in the community in a treatment program or on
parole after the treatment program has been
completed.
Paraphilia and paraphilia-related disorders are
more prevalent than most clinicians suspect. Since
these disorders are cloaked in shame and guilt, the
presence of these conditions may not be adequately
revealed until a therapeutic alliance is firmly established. Once a diagnosis is established, appropriate
education about possible behavioral therapies and
appropriate use of psychopharmacological agents
can improve the prognosis for these conditions.
Resources
ORGANIZATIONS

American Academy of Clinical Sexologists. 1929 18th St.,
N.W., Suite 1166, Washington, DC 20009. (202) 4622122.
American Association for Marriage and Family Therapy.
1133 15th St., NW Suite 300, Washington, DC 200052710. (202) 452-0109. <http://www.aamft.org>.

David James Doermann
3367

Sexual perversions

Treatment

Sexually transmitted diseases

women will develop pelvic inflammatory disease
(PID) as a result of chlamydia infection, a leading
cause of infertility.

Sexually transmitted diseases
Definition


Human papillomavirus (HPV). HPV causes genital
warts and is the single most important risk factor for
cervical cancer in women. Over 100 types of HPV
exist, but only about 30 of them can cause genital
warts and are spread through sexual contact. In some
instances, warts are passed from mother to child
during childbirth, leading to a potentially life-threatening condition for newborns in which warts
develop in the throat (laryngeal papillomatosis).



Genital herpes. Herpes is an incurable viral infection
thought to be one of the most common STDs in this
country. It is caused by one of two types of herpes
simplex viruses: HSV-1 (commonly causing oral
herpes) or HSV-2 (usually causing genital herpes).
The CDC estimates that 45 million Americans (one
out of every five individuals 12 years of age or older)
are infected with HSV-2; this number has increased
30% since the 1970s. HSV-2 infection is more common in women (one out of every four women) than
men (one out of every five men) and in African
Americans (45.9%) than Caucasians (17.6%).



Gonorrhea. The bacterium Neisseria gonorrhoeae is
the causative agent of gonorrhea and can be spread
by vaginal, oral, or anal contact. The CDC reports
that approximately 650,000 individuals are infected
with gonorrhea each year in the United States, with
132.2 infections per 100,000 individuals occurring in
1999. Approximately 75% of American gonorrhea
infections occur in persons aged 15 to 29 years old. In
1999, 75% of reported gonorrhea cases occurred
among African Americans.



Syphilis. Syphilis is a potentially life-threatening
infection that increases the likelihood of acquiring
or transmitting HIV. In 1998, the CDC reported
approximately 38,000 cases of syphilis in the United
States; this included 800 cases of congenital syphilis.
Congenital syphilis causes irreversible health problems or death in as many as 40% of all live babies
born to women with untreated syphilis.



Human immunodeficiencyvirus (HIV) infection.
In 2000, the CDC reported that 120,223 people in
the United States are HIV-positive and 426,350
are living with AIDS. In addition, approximately
1,000-2,000 children are born each year with
HIV infection. It is also estimated that 33 million
adults and 1.3 million children worldwide were
living with HIV/AIDS as of 1999 with 5.4 million
being newly infected that year. There is no cure for
this STD.

Sexually transmitted disease (STD) is a term used
to describe more than 20 different infections that are
transmitted through exchange of semen, blood, and
other body fluids; or by direct contact with the
affected body areas of people with STDs. Sexually
transmitted diseases are also called venereal diseases.

Description
The Centers for Disease Control and Prevention
(CDC) has reported that 85% of the most prevalent
infectious diseases in the United States are sexually
transmitted. The rate of STDs in this country is 50 to
100 times higher than that of any other industrialized
nation. One in four sexually active Americans will be
affected by an STD at some time in his or her life.
About 12 million new STD infections occur in the
United States each year. One in four occurs in someone between the ages of 16 and 19. Almost 65% of all
STD infections affect people under the age of 25.
Types of STDs
STDs can have very painful long-term consequences as well as immediate health problems. They
can cause:


birth defects



blindness



bone deformities



brain damage



cancer



heart disease



infertility and other abnormalities of the reproductive system



mental retardation



death

Some of the most common and potentially serious
STDs in the United States include:


Chlamydia. This STD is caused by the bacterium
Chlamydia trachomatis, a microscopic organism
that lives as a parasite inside human cells. Although
over 526,000 cases of chlamydia were reported in the
United States in 1997, the CDC estimates that nearly
three million cases occur annually because 75% of
women and 50% of men show no symptoms of the
disease after infection. Approximately 40% of

3368

GALE ENCYCLOPEDIA OF MEDICINE

Brand Name (Generic Name)

Possible Common Side Effects
Include:

Achromycin V (tetracyline
hydrochloride)

Blurred vision, headache, dizziness,
rash, hives, appetite loss, nausea and
vomiting
Behaviorial changes, diarrhea, hives,
nausea and vomiting
Nausea and vomiting, diarrhea, irritated skin
Itching (genital and/or rectal), nausea
and vomiting, appetite loss, diarrhea,
swelling
Diarrhea, nausea and vomiting, appetite loss, abdominal pain

Amoxil (amoxicillin)
Ceftin (cerfuroxime axetil)
Doryx (doxycycline hyclate)

E.E.S., E-Mycin, ERYC, EryTab, Erythrocin, Ilosone
(erthromycin)
Flagyl (metronidazole)
Floxin (ofloxacin)
Minocin (minocycline
hydrochloride)
Noroxin (norfloxacin)
Omnipen (ampicillin)
Penetrex (enoxacin)
Zithromax (azithromycin)
Zovirax (acyclovir)

Numbness, tingling sensation in
extremities, seizures
Genital itching, nausea and vomiting,
headache, diarrhea, dizziness
Blurred vision, anemia, hives, rash,
throat irritation
Headache, nausea, dizziness
Itching, rash, hives, peeling skin, nausea and vomiting
Nausea and vomiting
Nausea and vomiting, diarrhea,
abdominal pain
Fluid retention, headache, rash, tingling sensation

Social groups and STDs
STDs affect certain population groups more
severely than others. Women, young people, and
members of minority groups are particularly affected.
Women in any age bracket are more likely than men to
develop medical complications related to STDs. With
respect to racial and ethnic categories, the incidence of
syphilis is 60 times higher among African Americans
than among Caucasians, and four times higher in
Hispanics than in Anglos. According to the CDC, in
1999 African Americans accounted for 77% of the
total number of gonorrhea cases and nearly 46% of
all genital herpes cases.

Causes and symptoms
The symptoms of STDs vary somewhat according
to the disease agent (virus or bacterium), the sex of the
patient, and the body systems affected. The symptoms
of some STDs are easy to identify; others produce
infections that may either go unnoticed for some
time or are easy to confuse with other diseases.
GALE ENCYCLOPEDIA OF MEDICINE

Some symptoms of STDs affect the genitals and
reproductive organs:


A woman who has an STD may bleed when she is not
menstruating or has abnormal vaginal discharge.
Vaginal burning, itching, and odor are common,
and she may experience pain in her pelvic area while
having sex



A discharge from the tip of the penis may be a sign
that a man has an STD. Males may also have painful
or burning sensations when they urinate.



There may be swelling of the lymph nodes near the
groin area.



Both men and women may develop skin rashes,
sores, bumps, or blisters near the mouth or genitals.
Homosexual men frequently develop these symptoms in the area around the anus.

Other symptoms of STDs are systemic, which
means that they affect the body as a whole. These
symptoms may include:


fever, chills, and similar flu-like symptoms



skin rashes over large parts of the body



arthritis-like pains or aching in the joints



throat swelling and redness that lasts for three weeks
or longer

Diagnosis
A sexually active person who has symptoms of an
STD or who has had an STD or symptoms of infection
should be examined without delay by one of the following health care professionals:


a specialist in women’s health (gynecologist)



a specialist in disorders of the urinary tract and the
male sexual organs (urologist)



a family physician



a nurse practitioner



a specialist in skin disorders (dermatologist).
3369

Sexually transmitted diseases

Drugs Used To Treat STDS

Syphilis in particular can be confused with disorders
ranging from infectious mononucleosis to allergic reactions to prescription medications. In addition, the
incubation period of STDs varies. Some produce
symptoms close enough to the time of sexual contact—often less than 48 hours later%mdash;for the
patient to recognize the connection between the behavior and the symptoms. Others have a longer incubation period, so that the patient may not recognize the
early symptoms as those of a sexually transmitted
infection.

Sexually transmitted diseases

being diagnosed and treated by a physician, other
STD symptoms require immediate medical attention.
Antibiotics are prescribed to treat gonorrhea,
chlamydia, syphilis, and other STDs caused by bacteria. Although prompt diagnosis and early treatment
almost always cures these STDs, new infections can
develop if exposure continues or is renewed.Viral
infections can be treated symptomatically with antiviral medications.

Prognosis
Cultures on agar plates. (Photograph by T. McCarthy, Custom
Medical Stock Photo. Reproduced by permission.)

The diagnostic process begins with a thorough
physical examination and a detailed medical history
that documents the patient’s sexual history and
assesses the risk of infection.
The doctor or other healthcare professional will:


Describe the testing process. This includes all blood
tests and other tests that may be relevant to the
specific infection.



Explain the meaning of the test results.



Provide the patient with information regarding highrisk behaviors and any necessary treatments or
procedures.

The doctor may suggest that a patient diagnosed with
one STD be tested for others, as its possible to have more
than one STD at a time. One infection may hide the
symptoms of another or create a climate that fosters its
growth. At present, it is particularly important that persons who are HIV-positive be tested for syphilis as well.
Notification
The law in most parts of the United States
requires public health officials to trace and contact
the partners of persons with STDs. Minors, however,
can get treatment without their parents’ permission.
Public health departments in most states can provide
information about STD clinic locations; Planned
Parenthood facilities provide testing and counseling.
These agencies can also help with or assume the
responsibility of notifying sexual partners who must
be tested and may require treatment.

Treatment
Although self-care can relieve some of the pain of
genital herpes or genital warts that has recurred after
3370

The prognosis for recovery from STDs varies
among the different diseases. The prognosis for recovery from gonorrhea, syphilis, and other STDs caused
by bacteria is generally good, provided that the disease
is diagnosed early and treated promptly. Untreated
syphilis in particular can lead to long-term complications and disability. Viral STDs (genital herpes, genital warts, HIV) cannot be cured but must be treated on
a long-term basis to relieve symptoms and prevent lifethreatening complications.

Prevention
Vaccines
Vaccines for the prevention of hepatitis A and
hepatitis B are currently recommended for gay and
bisexual men, users of illegal drugs, health care workers, and others at risk of contracting these diseases.
Vaccines to prevent other STDs are being tested and
may be available within several years.
Lifestyle choices
The risk of becoming infected with an STD can be
reduced or eliminated by changing certain personal
behaviors. Abstaining from sexual relations or maintaining a mutually monogamous relationship with a
partner are legitimate options. It is also wise to avoid
sexual contact with partners who are known to be
infected with an STD, whose health status is
unknown, who abuse drugs, or who are involved in
prostitution.
Use of condoms and other contraceptives
Men or women who have sex with a partner of
known (or unsure) infection should make sure a new
condom is used every time they have genital, oral, or
anal contact. Used correctly and consistently, male
condoms provide good protection against HIV and
other STDs such as gonorrhea, chlamydia, and syphilis. Female condoms (lubricated sheaths inserted into
GALE ENCYCLOPEDIA OF MEDICINE

Chlamydia—A microorganism that resembles certain types of bacteria and causes several sexually
transmitted diseases in humans.
Condom—A thin sheath worn over the penis during
sexual intercourse to prevent pregnancy or the
transmission of STDs. There are also female
condoms.
Diaphragm—A dome-shaped device used to cover
the back of a woman’s vagina during intercourse in
order to prevent pregnancy.
Pelvic inflammatory disease (PID)—An inflammation of the tubes leading from a woman’s ovaries to
the uterus (the Fallopian tubes), caused by a bacterial infection. PID is a leading cause of fertility problems in women.
Venereal disease—Another term for sexually transmitted disease.

the vagina) have also been shown to be effective in
preventing HIV and other STDs. Condoms provide a
measure of protection against genital herpes, genital
warts, and hepatitis B.
Spermicides and diaphragms can decrease the risk
of transmission of some STDs. They do not protect
women from contracting HIV. Birth-control pills,
patches, or injections do not prevent STDs. Neither
do surgical sterilization or hysterectomy.
Hygienic measures
Urinating and washing the genital area with soap
and water immediately after having sex may eliminate
some germs before they cause infection. Douching,
however, can spread infection deeper into the womb.
It may also increase a woman’s risk of developing
pelvic inflammatory disease (PID).
Resources
ORGANIZATIONS

National STD Hotline. (800)227-8922.
Planned Parenthood Federation of America. (800 )230-7526.
<http://www.planned parenthood.org>.
OTHER

Sexually Transmitted Diseases. March 24, 2001.
<http://www.cdc.gov/nchstp/dstd/dstdp.html>.

Maureen Haggerty
GALE ENCYCLOPEDIA OF MEDICINE

Sexually transmitted diseases
cultures
Definition
Sexually transmitted diseases are infections spread
from person to person through sexual contact. A culture is a test in which a laboratory attempts to grow
and identify the microorganism causing an infection.

Purpose
Sexually transmitted diseases (STDs) produce
symptoms such as genital discharge, pain during urination, bleeding, pelvic pain, skin ulcers, or urethritis.
Often, however, they produce no immediate symptoms. Therefore, the decision to test for these diseases
must be based not only the presence of symptoms, but
on whether or not a person is at risk of having one or
more of the diseases. Activities, such as drug use and
sex with more than one partner, put a person at high
risk for these diseases.
STD cultures are necessary to diagnose certain
types of STDs. Only after the infection is diagnosed
can it be treated and further spread of the infection
prevented. Left untreated, consequences of these diseases range from discomfort to infertility to death. In
addition, these diseases, if present in a pregnant
woman, can be passed from mother to fetus.

Description
Gonorrhea, syphilis, chlamydia, chancroid, herpes,
human papillomavirus, human immunodeficiency
virus (HIV), and mycoplasma are common sexually
transmitted diseases. Not all are diagnosed with a
culture. For those that are, a sample of material is
taken from the infection site, placed in a sterile
container, and sent to the laboratory.
Bacterial cultures
In the laboratory, a portion of material from the
infection site is spread over the surface of several
different types of culture plates and placed in an incubator at body temperature for one to two days.
Bacteria present in the sample will multiply and
appear on the plates as visible colonies. They are identified by the appearance of their colonies and by the
results of biochemical tests and a gram stain. The
Gram stain is done by smearing part of a colony
onto a microscope slide. After it dries, the slide is
stained with purple and red stains, then examined
under a microscope. The color of stain picked up by
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Sexually transmitted diseases cultures

KEY TERMS

Sexually transmitted diseases cultures

the bacteria (purple or red), the shape (such as round
or rectangle), and the size provide valuable clues as to
the identity and which antibiotics might work best.
Bacteria that stain purple are called Gram-positive;
those that stain red are called gram-negative.
The result of the gram stain is available the same
day or in less than an hour if requested by the physician. An early report, known as a preliminary report,
is usually available after one day. This report will tell if
any microorganisms have been found yet, and if so,
their Gram stain appearance—for example, a Gramnegative rod or a gram-positive cocci. The final report,
usually available in one to seven days, includes complete identification and an estimate of the quantity of
the microorganisms isolated.
A sensitivity test, also called antibiotic susceptibility test, commonly done on bacteria isolated from
an infection site, is not always done on bacteria isolated from a sexually transmitted disease. These bacteria often are treated using antibiotics that are part of
a standard treatment protocol.
GONORRHEA. Neisseria gonorrhoeae, also called
gonococcus or GC, causes gonorrhea. It infects the
surfaces of the genitourinary tract, primarily the urethra in males and the cervix in females. On a gram
stain done on material taken from an infection site, the
bacteria appear as small gram-negative diplococci
(pairs of round bacteria) inside white blood cells.
Neisseria gonorrhoeae grows on a special culture
plate called Thayer-Martin (TM) media in an environment with low levels of oxygen and high levels of
carbon dioxide.

The best specimen from which to culture Neisseria
gonorrhoeae is a swab of the urethra in a male or the
cervix in a female. Other possible specimens include
vagina, body fluid discharge, swab of genital lesion, or
the first urine of the day. Final results usually are
available after two days. Rapid nonculture tests are
available to test for GC and provide results on the
same or following day.
CHANCROID. Chancroid is caused by Haemophilus
ducreyi. It is characterized by genital ulcers with nearby
swollen lymph nodes. The specimen is collected by
swabbing one of these pus-filled ulcers. The gram
stain may not be helpful as this bacteria looks just like
other Haemophilus bacteria. This bacteria only grows
on special culture plates, so the physician must request
a specific culture for a person who has symptoms
of chancroid. Even using special culture plates,
Haemophilus ducreyi is isolated from less than 80% of
the ulcers it infects. If a culture is negative, the physician
must diagnose chancroid based on the person’s

3372

symptoms and by ruling out other possible causes of
these symptoms, such as syphilis.
MYCOPLASMA. Three types of mycoplasma organisms cause sexually transmitted urethritis in males and
pelvic inflammatory disease and cervicitis in females:
Mycoplasma hominis, Mycoplasma gentialium, and
Ureaplasma urealyticum. These organisms require special culture plates and may take up to six days to grow.
Samples are collected from the cervix in a female, the
urethra or semen in a male, or urine.
SYPHILIS. Syphilis is caused by Treponema pallidum, one in a group of bacteria called spirochetes. It
causes ulcers or chancres at the site of infection. The
organism does not grow in culture. Using special techniques and stains, it is identified by looking at a sample
of the ulcer or chancre under the microscope. Various
blood tests also may be done to detect the treponema
organism.
CHLAMYDIA. Chlamydia is caused by the gramnegative baterium Chlamydia trachomatis. It is one of
the most common STDs in the United States and
generally appears in sexually active adolescents and
young adults. While chlamydia often does not have
any initial symptoms, it can, if left untreated, lead to
pelvic inflammatory disease and sterility. Samples are
collected from one or more of these infection sites:
cervix in a female, urethra in a male, or the rectum.
A portion of specimen is combined with a specific type
of cell and allowed to incubate. Special stains are
performed on the cultured cells, looking for evidence
of the chlamydia organism within the cells. A swab can
also be taken from the woman’s vulva. Men and
women can now be screened for Chlamydia with a
urine sample. Urine-based screening has increased
screening significantly, especially among men.

Viral cultures
To culture or grow a virus in the laboratory, a
portion of specimen is mixed with commercially prepared animal cells in a test tube. Characteristic
changes to the cells caused by the growing virus help
identify the virus. The time to complete a viral culture
varies with the type of virus. It may take several days
or up to several weeks.
HERPES VIRUS. Herpes simplex virus type 2 is the
cause of genital herpes. Diagnosis is usually made
based on the person’s symptoms. If a diagnosis needs
confirmation, a viral culture is performed using material taken from an ulcer. A Tzanck smear is a microscope test that can rapidly detect signs of herpes
infection in cells taken from an ulcer. The culture

GALE ENCYCLOPEDIA OF MEDICINE

HUMAN PAPILLOMAVIRUS. Human papillomavirus causes genital warts. This virus will not grow in
culture; the diagnosis is based on the appearance of the
warts and the person’s symptoms. In late 2003, the
U.S. Food and Drug Administration (FDA) approved
a human papillomavirus (HPV) DNA test with a Pap
smear for screening women age 30 and older. The
combined test would help physicians determine
which women were at extremely low risk for cervical
cancer and which should be more closely monitored.
HIV. Human immunodeficiency virus (HIV) is
usually diagnosed with a blood test. Cultures for
HIV are possible, but rarely needed for diagnosis.
However, newer rapid tests were developed in 2003
and approved by the FDA in 2004. These tests are
cheaper and can deliver results in as little as three
minutes. The FDA also approved an HIV test in
2004 that can detect HIV in saliva.

Preparation
Generally, the type of specimen depends on the
type of infection. Cultures always should be collected
before the person begins taking antibiotics. After collection of these specimens, each is placed into a sterile tube
containing a liquid in which the organism can survive
while in route to the laboratory. The new rapid HIV
tests rely on blood samples collected from a finger stick
or vein or on saliva collected from the mouth. Initial
results are not sent to a lab but are processed onsite.
Urethral specimen
Men should not urinate one hour before collection of a urethral specimen. The physician inserts a
sterile, cotton-tipped swab into the urethra.

KEY TERMS
Culture—A laboratory test done to grow and identify microorganisms causing infection.
Gram stain—Microsopic examination of a portion
of a bacterial colony or sample from an infection
site after it has been stained by special stains.
Certain bacteria pick up the purple stain; these
bacteria are called gram positive. Other bacteria
pick up the red stain; these bacteria are called gram
negative. The color of the bacteria, in addition to
their size and shape, provide clues as to the identity
of the bacteria.
Sensitivity test—A test that determines which antibiotics will kill the bacteria isolated from a
culture.
Vulva—The external part of the woman’s genital
organs, including the vaginal vestibule.

The physician inserts a sterile, cotton-tipped swab into
the vagina.
Anal specimen
The physician inserts a sterile, cotton-tipped swab
about 1 inch into the anus and rotates the swab for 30
seconds. Stool must not contaminate the swab.
Oropharynx (throat) specimen
The person’s tongue is held down with a tongue
depressor, as a healthcare worker moves a sterile,
cotton-tipped swab across the back of the throat and
tonsil region.
Urine specimen

Cervical specimen
Women should not douche or take a bath within
24 hours of collection of a cervical or vaginal culture.
The physician inserts a moistened, nonlubricated vaginal speculum. After the cervix is exposed, the physician removes the cervical mucus using a cotton ball.
Next, he or she inserts a sterile cotton-tipped swab into
the endocervical canal and rotates the swab with firm
pressure for about 30 seconds.
Vaginal specimen
Women should not douche or take a bath within
24 hours of collection of a cervical or vaginal culture.
GALE ENCYCLOPEDIA OF MEDICINE

To collect a ‘‘clean-catch’’ urine, the person first
washes the perineum, and the penis or labia and vulva.
He or she begins urinating, letting the first portion
pass into the toilet, then collecting the remainder into
a sterile container.

Normal results
These microorganisms are not found in a normal
culture. Many types of microorganisms, normally
found on a person’s skin and in the genitourinary
tract, may contaminate the culture. If a mixture of
these microorganisms grow in the culture, they are
reported as normal flora.
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Sexually transmitted diseases cultures

takes up to 14 days. In 2004, the FDA approved a
blood test to detect the antibodies to herpes virus.

Shaken baby syndrome

Abnormal results
If a person has a positive culture for one or more
of these microorganisms, treatment is started and his
or her sexual partners should be notified and tested.
Certain laws govern reporting and partner notification
of various STDs. After treatment is completed, the
person’s physician may want a follow-up culture to
confirm the infection is gone.

Shaken baby syndrome
Definition
Shaken baby syndrome (SBS) is a collective term
for the internal head injuries a baby or young child
sustains from being violently shaken.

Description
Resources
PERIODICALS

‘‘Answer Back: Is there a Vulval Swwab Test for
Chlamydia?’’ Pulse September 13, 2004: 100.
‘‘Approval Sought for HIV-1 Test that Detects Antibodies
in Oral Fluid or Plasma.’’ AIDS Weekly October 27,
2003: 23.
Boschert, Sherry. ‘‘Chlaymdia Urine Test: Males Still
Underscreened: Noninvasive Screening Test.’’ Pediatric
News August 2004: 10–12.
‘‘FDA Approves DNAwithPap for Screening Women
(Greater than or Equal to) Age 30).’’ Contemporary
OB/Gyn October 2003: 105.
‘‘FDA Approves OraQuick HIV-1/2 Test to Detect HIV-2 in
Oral Fluid.’’ Biotech Week July 21, 2004: 401.
Kaye, Donald. ‘‘FDA Approves Herpes Antibody
Test.’’ Clinical Infectious Diseases September 15,
2004: 1.
‘‘New HIV Rapid Test Is 100 Percent Accurate.’’ Health &
Medicine Week September 15, 2003: 194.
‘‘New Three-minute Rapid HIV Test Launched in the
United States.’’ Medical Devices & Surgical Technology
Week September 12, 2004: 102.
‘‘One-step HIV Test May Be Cheaper, Faster, Less
Wasteful.’’ Medical Letter on the CDC & FDA October
5, 2003: 5.
St. Lawrence, Janet S., et al. ‘‘STD Screening, Testing, Case
Reporting, and Clinical and Partner Notification
Practices: A National Survey of U.S. Physicians.’’ The
American Journal of Public Health November 2002:
1784.
ORGANIZATIONS

American Social Health Association. PO Box 13827,
Research Triangle Park, NC 27709. (800) 227-8922.
<http://sunsite.unc.edu/ASHA>.
Centers for Disease Control and Prevention. National
Center for HIV, STD, and TB Prevention. 1600 Clifton
Road NE, Atlanta, GA 30333. (404) 639-8000. <http://
www.cdc.gov/nchstp/od/nchstp.html>.

Nancy J. Nordenson
Teresa G. Odle

SGOT see Aspartate aminotransferase test
3374

Shaken baby syndrome was first described in
medical literature in 1972. Physicians earlier labeled
these injuries as accidental, but as more about child
abuse became known, more cases of this syndrome
were properly diagnosed.
Every year, nearly 50,000 children in the United
States are forcefully shaken by their caretakers. More
than 60% of these children are boys. The victims are
on average six to eight months old, but may be as old
as five years or as young as a few days.
Men are more likely than women to shake a
child; typically, these men are in their early 20s and
are the baby’s father or the mother’s boyfriend.
Women who inflict SBS are more likely to be babysitters or child care providers than the baby’s mother.
The shaking may occur as a response of frustration to
the baby’s inconsolable crying or as an action of
routine abuse.

Causes and symptoms
Infants and small children are especially vulnerable to SBS because their neck muscles are still too
weak to adequately support their disproportionately
large heads, and their young brain tissue and blood
vessels are extremely fragile. When an infant is vigorously shaken by the arms, legs, shoulders, or chest, the
whiplash motion repeatedly jars the baby’s brain with
tremendous force, causing internal damage and bleeding. While there may be no obvious external signs of
injury following shaking, the child may suffer internally from brain bleeding and bruising (called subdural
hemorrhage and hematoma); brain swelling and
damage (called cerebral edema); mental retardation;
blindness, hearing loss, paralysis, speech impairment,
and learning disabilities; and death. Nearly 2,000 children die every year as a result of being shaken.
Physicians may have difficulty initially diagnosing
SBS because there are usually few witnesses to give a
reliable account of the events leading to the trauma,
few if any external injuries, and, upon close examination, the physical findings may not agree with the
account given. A shaken baby may present one or
GALE ENCYCLOPEDIA OF MEDICINE

Shaken baby syndrome
Shaken baby syndrome is a collective term for the internal head injuries a baby or young child sustains from being violently
shaken. Because of the fragile state of an infant’s brain tissue and blood vessels, when a baby is vigorously shaken by the chest,
as shown in the illustration above, the whiplash motion repeatedly jars the baby’s brain with extreme force, causing serious
internal damage and bleeding. Nearly 2,000 American children die annually from this condition. (Illustration by Electronic
Illustrators Group.)

more signs, including vomiting; difficulty breathing,
sucking, swallowing, or making sounds; seizures; and
altered consciousness.

Diagnosis
To diagnose SBS, physicians look for at least one
of three classic conditions: bleeding at the back of one
or both eyes (retinal hemorrhage), subdural hematoma, and cerebral edema. The diagnosis is confirmed
by the results of either a computed tomography scan
(CT scan) or magnetic resonance imaging (MRI).

Treatment
Appropriate treatment is determined by the type
and severity of the trauma. Physicians may medically
manage both internal and external injuries. Behavioral
and educational impairments as a result of the injuries
require the attention of additional specialists.
Children with SBS may need physical therapy, speech
therapy, vision therapy, and special education
services.

Alternative treatment
There is no alternative to prompt medical treatment. An unresponsive child should never be put
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cerebral edema—Fluid collecting in the brain,
causing tissue to swell.
Hematoma—A localized accumulation of blood in
tissues as a result of hemorrhaging.
Hemorrhage—A condition of bleeding, usually
severe.
Retinal hemorrhage—Bleeding of the retina, a key
structure in vision located at the back of the eye.
Subdural hematoma—A localized accumulation of
blood, sometimes mixed with spinal fluid, in the
space of the brain beneath the membrane covering
called the dura mater.

to bed, but must be taken to a hospital for immediate
care.

Prognosis
Sadly, children who receive violent shaking have a
poor prognosis for complete recovery. Those who do
not die may experience permanent blindness, mental
retardation, seizure disorders, or loss of motor control.
3375

Shiatsu

Prevention

Purpose

Shaken baby syndrome is preventable with public
education. Adults must be actively taught that shaking
a child is never acceptable and can cause severe injury
or death.
When the frustration from an incessantly crying
baby becomes too much, caregivers should have a
strategy for coping that does not harm the baby. The
first step is to place the baby in a crib or playpen and
leave the room in order to calm down. Counting to 10
and taking deep breaths may help. A friend or relative
may be called to come over and assist. A calm adult
may then resume trying to comfort the baby. A warm
bottle, a dry diaper, soft music, a bath, or a ride in a
swing, stroller, or car may be offered to soothe a crying
child. Crying may also indicate pain or illness, such as
from abdominal cramps or an earache. If the crying
persists, the child should be seen by a physician.
Resources
ORGANIZATIONS

American Humane Association, Children’s Division. 63
Inverness Drive East, Englewood, CO 80112-5117.
(800) 227-4645. <www.americanhumane.org>.
Child Abuse Prevention Center of Utah. 2955 Harrison
Boulevard, #102, Ogden, UT 84403. (888) 273-0071.
National Center on Shaken Baby Syndrome. 2955 Harrison
Blvd., #102, Ogden, UT 84403. (801) 627-3399.
<http://www.dontshake.com>.

Bethany Thivierge

Shiatsu
Definition
Shiatsu is a manipulative therapy developed in
Japan and incorporating techniques of anma
(Japanese traditional massage), acupressure, stretching, and Western massage. Shiatsu involves applying
pressure to special points or areas on the body in order
to maintain physical and mental well being, treat disease, or alleviate discomfort. This therapy is considered holistic because it attempts to treat the whole
person instead of a specific medical complaint. All
types of acupressure generally focus on the same pressure points and so-called energy pathways, but may
differ in terms of massage technique. Shiatsu, which
can be translated as finger pressure, has been described
as needle-free acupuncture.
3376

Shiatsu has a strong reputation for reducing stress
and relieving nausea and vomiting. Shiatsu is also
believed to improve circulation and boost the immune
system. Some people use it to treat diarrhea, indigestion, constipation, and other disorders of the gastrointestinal tract; menstrual and menopausal problems;
chronic pain; migraine; arthritis; toothache; anxiety;
and depression. Shiatsu can be used to relieve muscular pain or tension, especially neck and back pain. It
also appears to have sedative effects and may alleviate
insomnia. In a broader sense, shiatsu is believed to
enhance physical vitality and emotional well being.

Description
Origins
Shiatsu is an offshoot of anma that developed
during the period after the Meiji Restoration in 1868.
Traditional massage (anma) used during the age of
shoguns was being criticized, and practitioners of
koho anma (ancient way) displeased with it introduced
new practices and new names for their therapies.
During the twentieth century, shiatsu distinguished itself from anma through the merging of
Western knowledge of anatomy, koho anma, ampuku
(abdominal massage), acupressure, Do-In (breathing
practices), and Buddhism. Based on the work of
Tamai Tempaku, shiatsu established itself in Japan
and worldwide. The Shiatsu Therapists Association
was founded in 1925 and clinics and schools followed.
Students of Tempaku began teaching their own brand
of shiatsu, creating branch disciplines. By 1955, the
Japanese Ministry of Health and Welfare acknowledged shiatsu as a beneficial treatment, and licensing
was established for practitioners.
Shiatsu and other forms of Japanese acupressure
are based on the concept of ki, the Japanese term for
the all-pervading energy that flows through everything
in the universe. (This notion is borrowed from the
Chinese, who refer to the omnipresent energy as qi or
chi.) Ki tends to flow through the body along special
energy pathways called meridians, each of which is
associated with a vital organ. In Asian systems of
traditional medicine, diseases are often believed to
occur due to disruptions in the flow this energy
through the body. These disruptions may stem from
emotional factors, climate, or a host of other causes
including stress, the presence of impurities in the body,
and physical trauma.
The aim of shiatsu is to restore the proper flow of
bodily energy by massaging the surface of the skin
GALE ENCYCLOPEDIA OF MEDICINE

Western medicine has not proven the existence of
meridians and acupoints. However, in one study, two
French medical doctors conducted an experiment at
Necher Hospital in Paris to test validity of the theory
that energy is being transported along acupuncture
meridians. They injected and traced isotpes with
gamma-camera imaging. The meridians may actually
correspond to nerve transmission lines. In this view,
shiatsu and other forms of healing massage may trigger
the emission of naturally occurring chemicals called
neurotransmitters. Release of these chemical messengers may be responsible for some of the therapeutic
effects associated with shiatsu, such as pain relief.

Preparations
People usually receive shiatsu therapy while lying
on a floor mat or massage table or sitting up. The
massage is performed through the clothing—preferably a thin garment made from natural fibers—and
disrobing is not required. Pressure is often applied
using the thumbs, though various other parts of the
body may be employed, including fingertips, palms,
knuckles, elbows, and knees—some therapists even
use their feet. Shiatsu typically consists of sustained
pressure (lasting up to 10 seconds at a time), squeezing, and stretching exercises. It may also involve gentle
holding as well as rocking motions. A treatment session lasts anywhere from 30 to 90 minutes.
Before shiatsu treatment begins, the therapist
usually performs a general health assessment. This
involves taking a family medical history and discussing the physical and emotional health of the person
seeking therapy. Typically, the practitioner also conducts a diagnostic examination by palpating the abdomen or back for any energy imbalances present in
other parts of the body.

Precautions
While shiatsu is generally considered safe, there are
a few precautions to consider. Because it may increase
blood flow, this type of therapy is not recommended in
people with bleeding problems, heart disease, or cancer.
GALE ENCYCLOPEDIA OF MEDICINE

Shiatsu

along the meridian lines. Pressure may also be applied
to any of the 600 or so acupoints. Acupoints, which are
supposedly located just under the skin along the meridians, are tiny energy structures that affect the flow of
ki through the body. When ki either stagnates and
becomes deflected or accumulates in excess along one
of these channels, stimulation to the acupoints, which
are sensitive to pressure, can unblock and regulate the
ki flow through toning or sedating treatment.

KEY TERMS
Acupressure—An ancient form of Asian healing
massage that involves applying pressure to special
points or areas on the body in order to maintain
good health, cure disease, and restore vitality.
Analgesic—Pain reliever.
Osteoporosis—A disease of the bones due to deficiency of bone matrix, occurring most frequently in
postmenopausal women.
Palpate—Feel.

Massage therapy should always be used with caution
in those with osteoporosis, fresh wounds or scar tissue,
bone fractures, or inflammation.
Applying pressure to areas of the head is not
recommended in people with epilepsy or high blood
pressure, according to some practitioners of shiatsu.
Shiatsu is not considered effective in the treatment
of fever, burns, and infectious diseases.
Shiatsu should not be performed right after a
meal.

Side effects
When performed properly, shiatsu is not associated with any significant side effects. Some people
may experience mild discomfort, which usually disappears during the course of the treatment session.

Research and general acceptance
Like many forms of massage, shiatsu is widely
believed to have a relaxing effect on the body. There is
also a significant amount of research suggesting that
acupressure techniques can relieve nausea and vomiting
associated with a variety of causes, including pregnancy
and anesthetics and other drugs. In one study, acupressure was shown to significantly reduce the effects of
nausea in 12 of 16 women suffering from morning sickness. Five days of this therapy also appeared to reduce
anxiety and improve mood. Another investigation, published in 1999, studied the effects of acupressure on
nausea resulting from the use of anesthetics. Pressure
applied to an acupoint on the inside of the wrist
appeared to alleviate nausea in patients who received
anesthetics during the course of laparoscopic surgery.
Shiatsu may also produce sedative and analgesic
effects. The sedative powers of acupressure were
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Shigellosis

investigated in a study published in the Journals of
Gerontology 1999, which involved over 80 elderly people who suffered from sleeping difficulties. Compared
to the people in the control groups, the 28 participants
who received acupressure were able to sleep better.
They slept for longer periods of time and were less likely
to wake up during the night. The researchers concluded
that acupressure may improve the quality of sleep in
older adults. The use of acupressure in postoperative
pain was investigated in a study published in 1996. In
this study, which involved 40 knee surgery patients, one
group received acupressure (15 acupoints were stimulated) while the control group received sham acupressure. Within an hour of treatment, members of the
acupressure group reported less pain than those in the
control group. The pain-relieving effects associated
with acupressure lasted for 24 hours.
Shiatsu may benefit stroke victims. The results of at
least one study (which did not include a control group)
suggest that shiatsu may be useful during stroke rehabilitation when combined with other treatments.
Resources
BOOKS

Cook, Allan R. Alternative Medicine Source book. Detroit:
Omnigraphics, 1999.
PERIODICALS

Chen, M.L., L.C. Lin, S.C. Wu, et al. ‘‘The effectiveness of
Acupressure in Improving the Quality of Sleep of
Institutionalized Residents.’’ J Gerontol A Biol Sci Med
Sci 1999: M389-94.
Harmon, D., J. Gardiner, R. Harrison, et al. ‘‘Acupressure
and the Prevention of nausea and vomiting after
laparoscopy.’’ Br J Anaesth 1999: 387-390
ORGANIZATIONS

Acupressure Institute. 1533 Shattuck Avenue, Berkeley, CA
94709.
American Massage Therapy Association. 820 Davis Street,
Suite 100, Evanston, IL. <http://
www.amtamassage.org>.
American Oriental Bodywork Therapy Association. 50
Maple Place, Manhassett, NY 11030.
International School of Shiatsu. 10 South Clinton Street,
Doylestown, PA 18901.
National Certification Board for Therapeutic Massage and
Bodywork. 8201 Greensboro Drive, Suite 300,
McLean, VA 22102.
OTHER

International School of Shiatsu. <http://
www.shiatsubo.com>.
MEDLINE. <http://igm.nlm.nih.gov>.

Greg Annussek
3378

Shigellosis
Definition
Shigellosis is an infection of the intestinal tract by a
group of bacteria called Shigella. The bacteria is named
in honor of Shiga, a Japanese researcher, who discovered the organism in 1897. The major symptoms are
diarrhea, abdominal cramps, fever, and severe fluid loss
(dehydration). Four different groups of Shigella can
affect humans; of these, S. dysenteriae generally produces the most severe attacks, and S. sonnei the mildest.

Description
Shigellosis is a well-known cause of traveler’s diarrhea and illness throughout the world. Shigella are
extremely infectious bacteria, and ingestion of just
10 organisms is enough to cause severe diarrhea and
dehydration. Shigella accounts for 10-20% of all cases
of diarrhea worldwide, and in any given year infects
over 140 million persons and kills 600,000, mostly
children and the elderly. The most serious form of
the disease is called dysentery, which is characterized
by severe watery (and often blood- and mucousstreaked) diarrhea, abdominal cramping, rectal pain,
and fever. Shigella is only one of several organisms
that can cause dysentery, but the term bacillary dysentery is usually another name for shigellosis.
Most deaths are in less-developed or developing
countries, but even in the United States, shigellosis can
be a dangerous and potentially deadly disease. Poor
hygiene, overcrowding, and improper storage of food
are leading causes of infection. The following statistics
show the marked difference in the frequency of cases
between developed and less-developed countries; in
the United States, about 30,000 individuals are hit by
the disease each year or about 10 cases/100,000 population. On the other hand, infection in some areas
of South America is 1,000 times more frequent.
Shigellosis is most common in children below age
five, and occurs less often in adults over 20.

Causes and symptoms
Shigella share several of the characteristics of a
group of bacteria that inhabit the intestinal tract.
E coli, another cause of food-borne illness, can be
mistaken for Shigella both by physicians and the
laboratory. Careful testing is needed to assure proper
diagnosis and treatment.
Shigella are very resistant to the acid produced by
the stomach, and this allows them to easily pass
GALE ENCYCLOPEDIA OF MEDICINE

Shigellosis

through the gastrointestinal tract and infect the colon
(large intestine). The result is a colitis that produces
multiple ulcers, which can bleed. Shigella also produce
a number of toxins (Shiga toxin and others) that increase
the amount of fluid secretion by the intestinal tract. This
fluid secretion is a major cause of the diarrhea symptoms.
Shigella infection spreads through food or water
contaminated by human waste. Sources of transmission are:


contaminated milk, ice cream, vegetables and other
foods which often cause epidemics



household contacts (40% of adults and 20% of children will develop infection from such a source)



poor hygiene and overcrowded living conditions



day care centers



sexual practices which lead to oral-anal contact,
directly or indirectly

Symptoms can be limited to only mild diarrhea or
go on to full-blown dysentery. Dehydration results from
the large fluid losses due to diarrhea, vomiting, and
fever. Inability to eat or drink worsens the situation.
In developed countries, most infections are of the
less severe type, and are often due to S. sonnei. The
period between infection and symptoms (incubation
period) varies from one to seven days. Shigellosis can
last from a few days to several weeks, with an average
of seven days.
Complications
Areas outside the intestine can be involved,
including:


nervous system (irritation of the meninges or meningitis, encephalitis, and seizures)



kidneys (producing hemolytic uremic syndrome or
HUS which leads to kidney failure)



joints (leading to an unusual form of arthritis called
Reiter’s syndrome)



skin (rash)

One of the most serious complications of this disease is HUS, which involves the kidney. The main findings are kidney failure and damage to red blood cells.
As many as 15% of patients die from this complication,
and half the survivors develop chronic kidney failure,
requiring dialysis.
Another life-threatening condition is toxic megacolon. Severe inflammation causes the colon to dilate
or stretch, and the thin colon wall may eventually tear.
Certain medications (particularly those that diminish
intestinal contractions) may increase this risk, but this
GALE ENCYCLOPEDIA OF MEDICINE

A transmission electron microscopy (TEM) scan of Shigella, a
genus of aerobic bacteria that causes dysentery in humans
and animals. (Custom Medical Stock Photo. Reproduced by
permission.)

interaction is unclear. Clues to this diagnosis include
sudden decrease in diarrhea, swelling of the abdomen,
and worsening abdominal pain.

Diagnosis
Shigellosis is one of the many causes of acute
diarrhea. Culture (growing the bacteria in the laboratory) of freshly obtained diarrhea fluid is the only way
to be certain of the diagnosis. But even this is not
always positive, especially if the patient is already on
antibiotics. Shigella are identified by a combination of
their appearance under the microscope and various
chemical tests. These studies take several days, so
quicker means to recognize the bacteria and its toxins
are being developed.

Treatment
The first aim of treatment is to keep up nutrition
and avoid dehydration. Ideally, a physician should be
consulted before starting any treatment. Antibiotics
may not be necessary, except for the more severe infections. Many cases resolve before the diagnosis is established by culture. Medications that control diarrhea by
slowing intestinal contractions can cause problems and
should be avoided by patients with bloody diarrhea or
fever, especially if antibiotics have not been started.
3379

Shigellosis

KEY TERMS
Dysentery—A disease marked by frequent watery
bowel movements, often with blood and mucus,
and characterized by pain, urgency to have a
bowel movement, fever, and dehydration.
Traveler’s diarrhea—An illness due to infection from
a bacteria or parasite that occurs in persons traveling
to areas where there is a high frequency of the illness.
The disease is usually spread by contaminated food
or water.
Oral Rehydration Solution(ORS)—A liquid preparation developed by the World Health Organization
that can decrease fluid loss in persons with diarrhea.
Originally developed to be prepared with materials
available in the home, commercial preparations
have recently come into use.
Antibiotic—A medication that is designed to kill or
weaken bacteria.
Anti-motility medications—Medications such as
loperamide (Imodium), dephenoxylate (Lomotil), or
medications containing codeine or narcotics which
decrease the ability of the intestine to contract. These
may worsen the condition of a patient with dysentery
or colitis.
Food-borne illness—A disease that is transmitted by
eating or handling contaminated food.

Rehydration
The World Health Organization (WHO) has developed guidelines for a standard solution taken by
mouth, and prepared from ingredients readily available
at home. This Oral Rehydration Solution (ORS)
includes salt, baking powder, sugar, orange juice, and
water. Commercial preparations, such as Pedialyte, are
also available. In many patients with mild symptoms,
this is the only treatment needed. Severe dehydration
usually requires intravenous fluid replacement.
Antibiotics
In the early and mid-1990s, researchers began to
realize that not all cases of bacterial dysentery needed
antibiotic treatment. Many patients improve without
such therapy, and therefore these drugs are indicated
only for treatment of moderate or severe disease,
as found in the tropics. Choice of antibiotic is based
on the type of bacteria found in the geographical area
and on laboratory results. Recommendations as
3380

Fluoroquinolones—A relatively new group of antibiotics that have had good success in treating infections with many gram-negative bacteria, such as
Shigella. One drawback is that they should not be
used in children under 17 years of age, because of
possible effect on bone or cartilage growth.
Dialysis—A form of treatment for patients with kidneys that do not function properly. The treatment
removes toxic wastes from the body that are normally removed by the kidneys.
Colitis—Inflammation of the colon or large bowel
which has several causes. The lining of the colon
becomes swollen, and ulcers often develop. The
ability of the colon to absorb fluids is also affected,
and diarrhea often results.
Carrier state—The continued presence of an organism (bacteria, virus, or parasite) in the body that does
not cause symptoms, but is able to be transmitted
and infect other persons.
Stool—Passage of fecal material; a bowel
movement.
Meninges—Outer covering of the spinal cord and
brain. Infection is called meningitis, which can
lead to damage to the brain or spinal cord and lead
to death.

of 1997 include ampicillin, sulfa derivatives such
as Trimethoprim-Sulfamethoxazole (TMP-SMX)
sold as Bactrim, or fluoroquinolones (such as
Ciprofloxacin which is not FDA approved for use
in children).

Prognosis
Many patients with mild infections need no specific treatment and recover completely. In those with
severe infections, antibiotics will decrease the length of
symptoms and the number of days bacteria appear in
the feces. In rare cases, an individual may fail to clear
the bacteria from the intestinal tract; the result is a
persistent carrier state. This may be more frequent in
AIDS (Acquired Immune Deficiency Syndrome)
patients. Antibiotics are about 90% effective in eliminating these chronic infections.
In patients who have suffered particularly severe
attacks, some degree of cramping and diarrhea can
last for several weeks. This is usually due to damage
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Shigellosis is an extremely contagious disease;
good hand washing techniques and proper precautions in food handling will help in avoiding spread
of infection. Children in day care centers need to
be reminded about hand washing during an outbreak to minimize spread. Shigellosis in schools or
day care settings almost always disappears when
holiday breaks occur, which sever the chain of
transmission.
Traveler’s diarrhea (TD)
Shigella accounts for about 10% of diarrhea illness in travelers to Mexico, South America, and the
tropics. Most cases of TD are more of a nuisance than
a life-threatening disease. However, bloody diarrhea is
an indication that Shigella may be responsible.
In some cases though, aside from ruining a well
deserved vacation, these infections can interrupt business conference schedules and, in the worst instances,
lead to a life-threatening illness. Therefore, researchers
have tried to find a safe, yet effective, way of preventing TD. Of course the best prevention is to follow
closely the rules outlined by the WHO and other
groups regarding eating fresh fruits, vegetables, and
other foods.
One safe and effective method of preventing TD
is the use of large doses of Pepto Bismol. Tablets are
now available which are easier for travel; usage must
start a few days before departure. Patients should be
aware that Bismuth will turn bowel movements
black.
Antibiotics have also proven to be highly effective
in preventing TD. They can also produce significant
side effects, and therefore a physician should be consulted before use. Like Pepto Bismol, antibiotics need
to be started before beginning travel.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

David Kaminstein, MD
GALE ENCYCLOPEDIA OF MEDICINE

Shin splints

to the intestinal tract, which requires some time to
heal. Since antibiotics can also produce a form of
colitis, this must be considered as a possible cause of
persistent or recurrent symptoms.

Shin splints
Definition
Shin splints refer to the sharp pains that occur
down the front of the lower leg. They are a common
complaint, particularly among runners and other
athletes.

Description
Shin splints may refer to a number of lower leg
complaints and injuries. In most cases, shin splints
refer to the pain that results from overload on the
tissues that connect muscles to the shin bone (tibia).
They also may come from the small bone of the lower
leg and ankle, called the fibula. The medical term for
shin splints is medial tibial stress syndrome.
Next to ankle sprains, shin splints are probably the
most common complaint of injury to the lower body.
Most shin splints occur in the front (anterior) portion
of the tibia; some also occur in the inside of the leg
along the tibia. Runners probably suffer shin splints
more than other people, but they also occur in people
who play basketball and tennis and those who walk
long distances, particularly on treadmills.

Causes and symptoms
The most common cause of shin splints is overdoing activities that constantly pound on the legs and
feet. This may include sports with many stops and
starts, running down hills or other tilted surfaces, or
repeated walking. Simply training too long or too
hard, especially without proper stretching and warmup, can cause shin splints. People with flat feet, high
arches, or feet that turn outward may be more prone to
shin splints. Shoes that are worn or don’t provide
proper foot support also add to the problem.

Diagnosis
The physician will check the leg for tenderness. If
the pain is in a single area of the tibia and hurts to the
touch, the cause may by a stress fracture. The physician may order an x ray to rule out a stress fracture,
but shin splints often can be diagnosed without
x rays.

Treatment
Physicians usually recommend a period of rest
for people with shin splints to let the area heal.
3381

Shingles



Strengthening muscles in the front lower leg (anterior
tibialis) with resistance exercises or by walking on the
heels three times daily for about 30 yards.



Wearing quality shoes with arch supports. Runners
should purchase new shoes about every 400 miles. A
podiatrist can design special arch supports or orthotics for people with flat feet.



Runs should be started at a slow pace and gradually
increased.



Athletes can cross-train in a sport that does not
impact the feet and lower legs as much, such as
swimming or riding a bicycle.

KEY TERMS
Podiatrist—A physician who specializes in the
medical care and treatment of the human foot.
Stress fracture—A hairline fracture (narrow crack
along the surface of a bone) that is caused by
repeated stress to the bone, such as from jogging,
rather than from a single heavy blow.

Usually, about three to four weeks is recommended,
though the time varies depending on the patient and
injury severity. Shin splints may be treated in
phases, beginning with absolute rest and gradual
return to activity. Ice and elevation of the foot
may be used to help relieve pain and swelling in
the first phase. If the person needs to keep in
shape, stretching and water exercises that keep the
foot from bearing weight may be allowed after
initial treatment. As the patient returns to normal
function, orthotic footwear and braces may be
added to prevent re-injury.

Alternative treatment
Various massage techniques may help speed up
recovery. Homeopathic physicians may recommend
Rhus tox. Those using alternative remedies should
ensure they are certified practitioners and should coordinate care with allopathic providers.

Resources
PERIODICALS

Metzi, Jordan D., Joshua A. Metzi. ‘‘ Shin Pain in an
Adolescent Soccer Player: A Case-based Look at ‘Shin
Splints’: Do you Care for Children Who Regularly Run
or Play Sports? Then You Should Have a Basic
Understanding of the Different Entities that Can Cause
Shin Pain. That List Includes Tibial Stress Injuries and
Exertional Compartment Syndrome.’’ Contemporary
Pediatrics (Sept. 2004):36–39.
‘‘Shunning Shin Splints.’’ Muscle & Fitness (Aug. 2003):38.
Smith, Ian. ‘‘World of Hurt.’’ Men’s Health (June 2003):40.
ORGANIZATIONS

American Academy of Podiatric Sports Medicine. P.O. Box
723, Rockville, MD 20853. 888-854-3338. http://
www.aapsm.org.
OTHER

Shin Splints.Foot.com Web site, 2005. http://www.foot.com/info/cond_cond_shin_splints.jsp.

Prognosis
With proper rest, management, and prevention,
people with shin splints can return to normal activity
in a few weeks or more. However, continuing to perform the activity that caused the shin splints can lead
to stress fractures of the tibia.

Prevention
Re-injury is most common in the first month after
return to normal activity, and patients who have had
shin splints should return to previous activities cautiously. The following can help prevent shin splints
from occurring in people who run and perform stop
and start physical activities:


Warming up and stretching calf muscles before running or jogging. A podiatrist specializing in sports
medicine or other sports medicine specialist may
recommend specific stretching exercises.

3382

Teresa G. Odle

Shingles
Definition
Shingles, also called herpes zoster or zona, gets its
name from both the Latin and French words for belt
or girdle and refers to girdle-like skin eruptions that
may occur on the trunk of the body. The virus that
causes chickenpox, the varicella zoster virus (VSV),
can become dormant in nerve cells after an episode
of chickenpox and later reemerge as shingles. Initially,
red patches of rash develop into blisters. Because the
virus travels along the nerve to the skin, it can damage
the nerve and cause it to become inflamed. This condition can be very painful. If the pain persists long after
GALE ENCYCLOPEDIA OF MEDICINE

Description
Any person who has had chickenpox can develop
shingles. Approximately 500,000 cases of shingles
occur every year in the United States, according to
the National Institute of Allergy and Infectious
Diseases (NIAID). Overall, approximately 20% of
those who had chickenpox as children develop shingles at some time in their lives. People of all ages, even
children, can be affected, but the incidence increases
with age. Newborn infants, bone marrow and other
transplant recipients, as well as indivduals with
immune systems weakened by disease or drugs are
also at increased risk. However, most individuals
who develop shingles do not have any underlying
malignancy or other immunosuppressive condition.



itching, tingling, or severe burning pain



red patches that develop into blisters



grouped, dense, deep, small blisters that ooze and
crust



swollen lymph nodes

Diagnosis
Diagnosis is usually not possible until the skin
lesions develop. Once they develop, however, the pattern and location of the blisters and the type of cell
damage displayed are characteristic of the disease,
allowing an accurate diagnosis primarily based upon
the physical examination.
Although tests are rarely necessary, they may
include the following:


viral culture of skin lesion



microscopic examination using a Tzanck preparation. This involves staining a smear obtained from a
blister. Cells infected with the herpes virus will
appear very large and contain many dark cell centers
or nuclei.



complete blood count (CBC) may show an elevated
white blood cell count (WBC), a nonspecific sign of
infection



Rise in antibody to the virus



Polymerase chain reaction (PCR) analysis. PCR testing has been found to be much faster and significantly more accurate than culturing the virus.

Causes and symptoms
Shingles erupts along the course of the affected
nerve, producing lesions anywhere on the body and
may cause severe nerve pain. The most common areas
to be affected are the face and trunk, which correspond to the areas where the chickenpox rash is most
concentrated. The disease is caused by a reactivation
of the chickenpox virus that has lain dormant in certain nerves following an episode of chickenpox.
Exactly how or why this reactivation occurs is not
clear; however, it is believed that the reactivation is
triggered when the immune system becomes weakened, either as a result of stress, fatigue, certain medications, chemotherapy, or diseases, such as cancer or
HIV. Further, it can be an early sign in persons with
HIV that the immune system has deteriorated.
In some cases, the virus appears to be reactivated
by mechanical irritation or minor surgical procedures.
In one instance, the patient had an attack of shingles
following liposuction.
Early signs of shingles are often vague and can
easily be mistaken for other illnesses. The condition
may begin with fever and malaise (a vague feeling of
weakness or discomfort). Within two to four days,
severe pain, itching, and numbness/tingling (paresthesia) or extreme sensitivity to touch (hyperesthesia) can
develop, usually on the trunk and occasionally on the
arms and legs. Pain may be continuous or intermittent,
usually lasting from one to four weeks. It may occur at
the time of the eruption, but can precede the eruption
by days, occasionally making the diagnosis difficult.
Signs and symptoms may include the following:
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Shingles almost always resolves spontaneously
and may not require any treatment except for the relief
of symptoms. In most people, the condition clears on
its own in one or two weeks and seldom recurs.
Cool, wet compresses may help reduce pain. If
there are blisters or crusting, applying compresses
made with diluted vinegar will make the patient more
comfortable. Mix one-quarter cup of white vinegar in
two quarts of lukewarm water. Use the compress twice
each day for 10 minutes. Stop using the compresses
when the blisters have dried up.
Soothing baths and lotions such as colloidal oatmeal baths, starch baths or lotions, and calamine
lotion may help to relieve itching and discomfort.
Keep the skin clean, and do not re-use contaminated
items. While the lesions continue to ooze, the person
should be isolated to prevent infecting other susceptible individuals.
3383

Shingles

the rash disappears, it is known as postherpetic
neuralgia.

Shingles

(postherpetic neuralgia). This pain can be excruciating. Consequently, the doctor may prescribe tranquilizers, sedatives, or antidepressants to be taken at
night. As noted above attempts to treat postherpetic
neuralgia with the antiviral drug famciclovir have
shown some promising results. When all else fails,
severe pain may require a permanent nerve block.
A newer medication to treat postherpectic neuralgia is pregabalin, to be marketed in the United States
under the trade name Lyrica. Pregabalin was
approved by the Food and Drug Administration in
September 2004 for the treatment of diabetic neuropathy as well as postherpetic neuralgia. The drug has
been shown to improve patients’ sleep and overall
quality of life as well as relieve pain. Its most common
side effects are drowsiness, headache, dry mouth, and
dizziness.

Alternative treatment
Shingles, or herpes zoster, on patient’s buttocks and thigh.
(Custom Medical Stock Photo. Reproduced by permission.)

Later, when the crusts and scabs are separating,
the skin may become dry, tight, and cracked. If that
happens, rub on a small amount of plain petroleum
jelly three or four times a day.
The antiviral drugs acyclovir, valacyclovir, and
famciclovir can be used to treat shingles. These drugs
may shorten the course of the illness. Their use results
in more rapid healing of the blisters when drug therapy
is started within 72 hours of the onset of the rash. In
fact, the earlier the drugs are administered, the better,
because early cases can sometimes be stopped. If taken
later, these drugs are less effective but may still lessen
the pain. Antiviral drug treatment does not seem to
reduce the incidence of postherpetic neuralgia, but
recent studies suggest famciclovir may cut the duration of postherpetic neuralgia in half. Side effects of
typical oral doses of these antiviral drugs are minor
with headache and nausea reported by 8–20 % of
patients. Severely immunocompromised individuals,
such as those with AIDS, may require intravenous
administration of antiviral drugs.
Corticosteroids, such as prednisone, may be used
to reduce inflammation but they do interfere with the
functioning of the immune system. Corticosteroids, in
combination with antiviral therapy, also are used to
treat severe infections, such as those affecting the eyes,
and to reduce severe pain.
Once the blisters are healed, some people continue
to experience pain for months or even years
3384

There are nonmedical methods of prevention and
treatment that may speed recovery. For example, getting lots of rest, eating a healthy diet, exercising regularly, and minimizing stress are always helpful in
preventing disease. Supplementation with vitamin
B12 during the first one to two days and continued
supplementation with vitamin B complex, high levels
of vitamin C with bioflavenoids, and calcium, are
recommended to boost the immune system. Herbal
antivirals such as echinacea can be effective in fighting
infection and boosting the immune system.
Although no single alternative approach, technique, or remedy has yet been proven to reduce the pain,
there are a few options which may be helpful. For
example, topical applications of lemon balm (Melissa
officinalis ) or licorice (Glycyrrhiza glabra) and peppermint (Mentha piperita) may reduce pain and blistering.
Homeopathic remedies include Rhus toxicodendron for
blisters, Mezereum and Arsenicum album for pain, and
Ranunculus for itching. Practitioners of Eastern medicine recommend self-hypnosis, acupressure, and acupuncture to alleviate pain.

Prognosis
Shingles usually clears up in two to three weeks
and rarely recurs. Involvement of the nerves that cause
movement may cause a temporary or permanent nerve
paralysis and/or tremors. The elderly or debilitated
patient may have a prolonged and difficult course.
For them, the eruption is typically more extensive
and inflammatory, occasionally resulting in blisters
that bleed, areas where the skin actually dies,
GALE ENCYCLOPEDIA OF MEDICINE

Acyclovir—An antiviral drug that is available
under the trade name Zovirax, in oral, intravenous,
and topical forms. The drug blocks the replication
of the varicella zoster virus.
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Corticosteroid—A steroid that has similar properties to the steroid hormone produced by the adrenal
cortex. It is used to alter immune responses to
shingles.
Famciclovir—An oral antiviral drug that is available under the trade name Famvir. The drug blocks
the replication of the varicella zoster virus.
Immunocompromised—A state in which the
immune system is suppressed or not functioning
properly.
Postherpetic neuralgia (PHN)—The term used to
describe the pain after the rash associated with
herpes zoster is gone.
Tzanck preparation—Procedure in which skin
cells from a blister are stained and examined
under the microscope. Visualization of large skin
cells with many cell centers or nuclei indicates a
positive diagnosis of herpes zoster when combined
with results from a physical examination.
Valacyclovir—An oral antiviral drug that is available under the trade name Valtrex. The drug blocks
the replication of the varicella zoster virus.

secondary bacterial infection, or extensive and permanent scarring.
Similarly, an immunocompromised patient
usually has a more severe course that is frequently
prolonged for weeks to months. They develop shingles
frequently and the infection can spread to the skin,
lungs, liver, gastrointestinal tract, brain, or other vital
organs. Cases of chronic shingles have been reported
in patients infected with AIDS, especially when they
have a decreased number of one particular kind of
immune cell, called CD4 lymphocytes. Depletion of
CD4 lymphocytes is associated with more severe,
chronic, and recurrent varicella-zoster virus infections. These lesions are typical at the onset but may
turn into ulcers that do not heal.
Potentially serious complications can result from
herpes zoster. Many individuals continue to
GALE ENCYCLOPEDIA OF MEDICINE

experience persistent pain long after the blisters heal.
This pain, called postherpetic neuralgia or PHN, can
be severe and debilitating. Postherpetic neuralgia can
persist for months or years after the lesions have disappeared. The incidence of postherpetic neuralgia
increases with age, and episodes in older individuals
tend to be of longer duration. Most patients under 30
years of age experience no persistent pain. By age 40,
the risk of prolonged pain lasting longer than one
month increases to 33%. By age 70, the risk increases
to 74%. The pain can adversely affect quality of life,
but it does usually diminish over time. Another risk
factor for PHN is female sex.
Other complications include a secondary bacterial
infection, and rarely, potentially fatal inflammation of
the brain (encephalitis) and the spread of an infection
throughout the body. These rare, but extremely serious, complications are more likely to occur in those
individuals who have weakened immune systems
(immunocompromised).

Prevention
Strengthening the immune system by making lifestyle changes is thought to help prevent the development of shingles. A lifestyle designed to strengthen the
immune system and maintain good overall health
includes eating a well-balanced diet rich in essential
vitamins and minerals, getting enough sleep, exercising
regularly, and reducing stress.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Herpesvirus Infections.’’ Section 13, Chapter 162 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Andrews, T. R., G. Perdikis, and R. B. Shack. ‘‘Herpes
Zoster as a Rare Complication of Liposuction.’’ Plastic
and Reconstructive Surgery 113 (May 2004): 1838–1840.
Feder, H. M. Jr., and D. M. Hoss. ‘‘Herpes Zoster in
Otherwise Healthy Children.’’ Pediatric Infectious
Disease Journal 451–457.
Jung, B. F., R. W. Johnson, D. R. Griffin, and R. H.
Dworkin. ‘‘Risk Factors for Postherpetic Neuralgia in
Patients with Herpes Zoster.’’ Neurology 62 (May 11,
2004): 1545–1551.
Sabatowski, R., R. Galvez, D. Cherry, et al. ‘‘Pregabalin
Reduces Pain and Improves Sleep and Mood
Disturbances in Patients with Postherpetic Neuralgia:
Results of a Randomised, Placebo-Controlled Clinical
Trial.’’ Pain 109 (May 2004): 26–35.
3385

Shingles

KEY TERMS

Shock

Stranska, R., R. Schuurman, M. de Vos, and A. M. van
Loon. ‘‘Routine Use of a Highly Automated and
Internally Controlled Real-Time PCR Assay for the
Diagnosis of Herpes Simplex and Varicella-Zoster
Virus Infections.’’ Journal of Clinical Virology 30 (May
2004): 39–44.
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
National Institute of Allergy and Infectious Diseases
(NIAID). Office of Communications and Public
Liaison, 6610 Rockledge Drive, MSC 6612, Bethesda,
MD 20892-6612. <http://www.niaid.nih.gov>.

David James Doermann
Rebecca J. Frey, PhD

Shock
Definition
Shock is a medical emergency in which the organs
and tissues of the body are not receiving an adequate
flow of blood. This deprives the organs and tissues of
oxygen (carried in the blood) and allows the buildup of
waste products. Shock can result in serious damage or
even death.

Description
There are three stages of shock: Stage I (also
called compensated, or nonprogressive), Stage II
(also called decompensated or progressive), and
Stage III (also called irreversible).
In Stage I of shock, when low blood flow (perfusion) is first detected, a number of systems are activated
in order to maintain/restore perfusion. The result is that
the heart beats faster, the blood vessels throughout the
body become slightly smaller in diameter, and the kidney works to retain fluid in the circulatory system. All
this serves to maximize blood flow to the most important organs and systems in the body. The patient in this
stage of shock has very few symptoms, and treatment
can completely halt any progression.
In Stage II of shock, these methods of compensation begin to fail. The systems of the body are unable
to improve perfusion any longer, and the patient’s
symptoms reflect that fact. Oxygen deprivation in the
brain causes the patient to become confused and
3386

disoriented, while oxygen deprivation in the heart
may cause chest pain. With quick and appropriate
treatment, this stage of shock can be reversed.
In Stage III of shock, the length of time that poor
perfusion has existed begins to take a permanent toll
on the body’s organs and tissues. The heart’s functioning continues to spiral downward, and the kidneys
usually shut down completely. Cells in organs and
tissues throughout the body are injured and dying.
The endpoint of Stage III shock is the patient’s death.

Causes and symptoms
Shock is caused by three major categories of problems: cardiogenic (meaning problems associated with
the heart’s functioning); hypovolemic (meaning that
the total volume of blood available to circulate is low);
and septic shock (caused by overwhelming infection,
usually by bacteria).
Cardiogenic shock can be caused by any disease,
or event, which prevents the heart muscle from pumping strongly and consistently enough to circulate the
blood normally. Heart attack, conditions which cause
inflammation of the heart muscle (myocarditis), disturbances of the electrical rhythm of the heart, any
kind of mass or fluid accumulation and/or blood clot
which interferes with flow out of the heart can all
significantly affect the heart’s ability to adequately
pump a normal quantity of blood.
Hypovolemic shock occurs when the total volume
of blood in the body falls well below normal. This can
occur when there is excess fluid loss, as in dehydration
due to severe vomiting or diarrhea, diseases which
cause excess urination (diabetes insipidus, diabetes
mellitus, and kidney failure), extensive burns, blockage
in the intestine, inflammation of the pancreas (pancreatitis), or severe bleeding of any kind.
Septic shock can occur when an untreated or
inadequately treated infection (usually bacterial) is
allowed to progress. Bacteria often produce poisonous
chemicals (toxins) which can cause injury throughout
the body. When large quantities of these bacteria, and
their toxins, begin circulating in the bloodstream,
every organ and tissue in the body is at risk of their
damaging effects. The most damaging consequences
of these bacteria and toxins include poor functioning
of the heart muscle; widening of the diameter of the
blood vessels; a drop in blood pressure; activation of
the blood clotting system, causing blood clots, followed by a risk of uncontrollable bleeding; damage
to the lungs, causing acute respiratory distress syndrome; liver failure; kidney failure; and coma.
GALE ENCYCLOPEDIA OF MEDICINE

Cardiogenic—Originating with the heart.
Deprivation—A condition of having too little of
something.
Hypovolemic—Having a low volume.
Perfusion—Blood flow through an organ or tissue.
Sepsis—An overwhelming infection throughout the
body, usually caused by bacteria in the
bloodstream.

Initial symptoms of shock include cold, clammy
hands and feet; pale or blue-tinged skin tone; weak,
fast pulse rate; fast rate of breathing; low blood pressure. A variety of other symptoms may be present, but
they are dependent on the underlying cause of shock.

begun, the underlying condition causing shock, and
the general medical state of the patient.

Prevention
The most preventable type of shock is caused by
dehydration during illnesses with severe vomiting or
diarrhea. Shock can be avoided by recognizing that a
patient who is unable to drink in order to replace lost
fluids needs to be given fluids intravenously (through a
needle in a vein). Other types of shock are only preventable insofar as one can prevent their underlying
conditions, or can monitor and manage those conditions well enough so that they never progress to the
point of shock.
Resources
PERIODICALS

Kerasote, Ted. ‘‘After Shock: Recognizing and Treating
Shock.’’Sports Afield 217 (May 1997): 60+.

Rosalyn Carson-DeWitt, MD

Diagnosis
Diagnosis of shock is based on the patient’s symptoms, as well as criteria including a significant drop in
blood pressure, extremely low urine output, and blood
tests that reveal overly acidic blood with a low circulating
concentration of carbon dioxide. Other tests are performed, as appropriate, to try to determine the underlying
condition responsible for the patient’s state of shock.

Treatment
The most important goals in the treatment of
shock include: quickly diagnosing the patient’s state
of shock; quickly intervening to halt the underlying
condition (stopping bleeding, re-starting the heart,
giving antibiotics to combat an infection, etc.); treating
the effects of shock (low oxygen, increased acid in the
blood, activation of the blood clotting system); and
supporting vital functions (blood pressure, urine flow,
heart function).
Treatment includes keeping the patient warm,
with legs raised and head down to improve blood
flow to the brain, putting a needle in a vein in order
to give fluids or blood transfusions, as necessary; giving the patient extra oxygen to breathe and medications to improve the heart’s functioning; and treating
the underlying condition which led to shock.

Prognosis
The prognosis of an individual patient in shock
depends on the stage of shock when treatment was
GALE ENCYCLOPEDIA OF MEDICINE

Shock l see Adult respiratory distress
syndrome
Shock therapy see Electroconvulsive therapy

Shortness of breath
Definition
Shortness of breath, or dyspnea, is a feeling of
difficult or labored breathing that is out of proportion
to the patient’s level of physical activity. It is a symptom of a variety of different diseases or disorders and
may be either acute or chronic.

Description
The experience of dyspnea depends on its severity
and underlying causes. The feeling itself results from a
combination of impulses relayed to the brain from
nerve endings in the lungs, rib cage, chest muscles, or
diaphragm, combined with the patient’s perception
and interpretation of the sensation. In some cases,
the patient’s sensation of breathlessness is intensified
by anxiety about its cause. Patients describe dyspnea
variously as unpleasant shortness of breath, a feeling
of increased effort or tiredness in moving the chest
muscles, a panicky feeling of being smothered, or a
sense of tightness or cramping in the chest wall.
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Shortness of breath

KEY TERMS

Shortness of breath

Causes and symptoms
ACUTE DYSPNEA. Acute dyspnea with sudden
onset is a frequent cause of emergency room visits.
Most cases of acute dyspnea involve pulmonary
(lung and breathing) disorders, cardiovascular disease, or chest trauma.
PULMONARY DISORDERS. Pulmonary disorders
that can cause dyspnea include airway obstruction by
a foreign object, swelling due to infection, or anaphylactic shock; acute pneumonia; hemorrhage from the
lungs; or severe bronchospasms associated with
asthma.
CARDIOVASCULAR DISEASE. Acute dyspnea can be

caused by disturbances of the heart rhythm, failure of
the left ventricle, mitral valve (a heart valve) dysfunction, or an embolus (a clump of tissue, fat, or gas) that
is blocking the pulmonary circulation. Most pulmonary emboli (blood clots) originate in the deep veins of
the lower legs and eventually migrate to the pulmonary artery.
TRAUMA. Chest injuries, both closed injuries and
penetrating wounds, can cause pneumothorax (the presence of air inside the chest cavity), bruises, or fractured ribs. Pain from these injuries results in dyspnea.
The impact of the driver’s chest against the steering
wheel in auto accidents is a frequent cause of closed
chest injuries.
OTHER CAUSES. Anxiety attacks sometimes cause
acute dyspnea; they may or may not be associated with
chest pain. Anxiety attacks are often accompanied by
hyperventilation, which is a breathing pattern characterized by abnormally rapid and deep breaths.
Hyperventilation raises the oxygen level in the blood,
causing chest pain and dizziness.

muscular dystrophy, myasthenia gravis, and amyotrophic lateral sclerosis.
OTHER CAUSES. Patients who are severely anemic
may develop dyspnea if they exercise vigorously.
Hyperthyroidism or hypothyroidism may cause shortness of breath, and so may gastroesophageal reflux
disease (GERD). Both chronic anxiety disorders z of
physical fitness can also cause episodes of dyspnea.
Deformities of the chest or obesity can cause dyspnea
by limiting the movement of the chest wall and the
ability of the lungs to fill completely.

Diagnosis
Patient history
The patient’s history provides the doctor with such
necessary information as a history of gastroesophageal
reflux disease (GERD), asthma, or other allergic conditions; the presence of chest pain as well as difficulty
breathing; recent accidents or recent surgery; information about smoking habits; the patient’s baseline level of
physical activity and exercise habits; and a psychiatric
history of panic attacks or anxiety disorders.
ASSESSMENT OF BODY POSITION. How a person’s
body position affects his/her dyspnea symptoms sometimes gives hints as to the underlying cause of the
disorder. Dyspnea that is worse when the patient is
sitting up is called platypnea and indicates the possibility of liver disease. Dyspnea that is worse when the
patient is lying down is called orthopnea, and is associated with heart disease or paralysis of the diaphragm. Paroxysmal nocturnal dyspnea (PND)
refers to dyspnea that occurs during sleep and forces
the patient to awake gasping for breath. It is usually
relieved if the patient sits up or stands. PND may point
to dysfunction of the left ventricle of the heart, hypertension, or narrowing of the mitral valve.

Chronic dyspnea
PULMONARY DISORDERS. Chronic dyspnea can be

caused by asthma, chronic obstructive pulmonary disease (COPD), bronchitis, emphysema, inflammation of
the lungs, pulmonary hypertension, tumors, or disorders of the vocal cords.
HEART DISEASE. Disorders of the left side of the
heart or inadequate supply of blood to the heart muscle can cause dyspnea. In some cases a tumor in the
heart or inflammation of the membrane surrounding
the heart may cause dyspnea.
NEUROMUSCULAR
DISORDERS. Neuromuscular
disorders cause dyspnea from progressive deterioration of the patient’s chest muscles. They include

3388

Physical examination
The doctor will examine the patient’s chest in
order to determine the rate and depth of breathing,
the effort required, the condition of the patient’s
breathing muscles, and any evidence of chest deformities or trauma. He or she will listen for wheezing,
stridor, or signs of fluid in the lungs. If the patient
has a fever, the doctor will look for other signs of
pneumonia. The doctor will check the patient’s heart
functions, including blood pressure, pulse rate, and
the presence of heart murmurs or other abnormal
heart sounds. If the doctor suspects a blood clot in
one of the large veins leading to the heart, he or she will
examine the patient’s legs for signs of swelling.
GALE ENCYCLOPEDIA OF MEDICINE

BASIC DIAGNOSTIC TESTS. Patients who are seen in
emergency rooms are given a chest x ray and electrocardiogram (ECG) to assist the doctor in evaluating
abnormalities of the chest wall, also to determine the
position of the diaphragm, possible rib fractures or
pneumothorax, irregular heartbeat, or the adequacy
of the supply of blood to the heart muscle. Also, the
patient may be given a breathing test on an instrument
called a spirometer to screen for airway disorders.

The doctor may order blood tests and arterial
blood gas tests to rule out anemia, hyperventilation–
from an anxiety attack –, or thyroid dysfunction. A
sputum culture can be used to test for pneumonia.
SPECIALIZED TESTS. Specialized tests may be ordered
for patients with normal results from basic diagnostic
tests for dyspnea. High-resolution CT scans can be used
for suspected airway obstruction or mild emphysema.
Tissue biopsy performed with a bronchoscope can be
used for patients with suspected lung disease.

If the doctor suspects a pulmonary embolism, he or
she may order ventilation-perfusion scanning to
inspect lung function, an angiogram of blood vessels,
or ultrasound studies of the leg veins.
Echocardiography can be used to test for pulmonary
hypertension and heart disease.
Pulmonary function studies or electromyography
(EMG) are used to assess neuromuscular diseases.
Exercise testing is used to assess dyspnea related to
COPD, anxiety attacks, poor physical fitness, and the
severity of lung or heart disease. The level of acidity in
the patient’s esophagus may be monitored to rule out
GERD.

Treatment
Treatment of dyspnea depends on its underlying
cause.
Acute dyspnea
Patients with acute dyspnea are given oxygen in
the emergency room, with the following treatments for
specific conditions:


Asthma. Treatment with Alupent, epinephrine, or
aminophylline.



Anaphylactic shock. Treatment with Benadryl, steroids, or aminophylline, with hydrocortisone if
necessary.



Congestive heart failure. Treatment with oxygen,
diuretics, and placing patient in upright position.

GALE ENCYCLOPEDIA OF MEDICINE



Pneumonia. Treatment with antibiotics and removal
of lung secretions.



Anxiety attacks. Immediate treatment includes antidepressant medications. If the patient is hyperventilating, he or she may be asked to breathe into a paper
bag to normalize breathing rhythm and the oxygen
level of the blood.



Pneumothorax. Surgical placement of a chest tube.
Chronic dyspnea

The treatment of chronic dyspnea depends on the
underlying disorder. Asthma can often be managed
with a combination of medications to reduce airway
spasms and removal of allergens from the patient’s
environment. COPD requires both medication, lifestyle changes, and long-term physical rehabilitation.
Anxiety disorders are usually treated with a combination of medication and psychotherapy. GERD can
usually be managed with antacids, other medications,
and dietary changes. There are no permanent cures for
myasthenia gravis or muscular dystrophy.
Tumors and certain types of chest deformities can
be treated surgically.

Alternative treatment
The appropriate alternative therapy for shortness
of breath depends on the underlying cause of the condition. When dyspnea is acute and severe, oxygen
therapy is used either in the doctor’s office or in the
emergency room. For shortness of breath with an
underlying physical cause like asthma, anaphylactic
shock, or pneumonia, the physical condition should
be treated. Botanical and homeopathic remedies can
be used for acute dyspnea, if the proper remedies and
formulas are prescribed. If the dyspnea has a psychological basis (especially if it is caused by anxiety),
acupuncture, botanical medicine, and homeopathy
can help the patient heal at a deep level.

Prognosis
The prognosis for recovery depends on the underlying cause of the dyspnea, its severity, and the type of
treatment required.

Prevention
Dyspnea caused by asthma can be minimized or
prevented by removing dust and other triggers from
the patient’s environment. Long-term prevention of
chronic dyspnea includes such lifestyle choices as regular aerobic exercise and avoidance of smoking.
3389

Shortness of breath

Diagnostic tests

Shy-Drager syndrome

KEY TERMS
Anaphylactic shock—A severe systemic reaction to
an allergen that occurs in hypersensitive individuals. It can cause spasms of the larynx that block
the patient’s airway and cause dyspnea.
Dyspnea—A sensation of difficult or labored
breathing.
Electromyography—A technique for recording
electric currents in an active muscle in order to
measure its level of function.
Orthopnea—Difficulty in breathing that occurs
while the patient is lying down.
Paroxysmal nocturnal dyspnea (PND)—A form of
dyspnea characterized by the patient’s waking
from sleep unable to breathe.
Platypnea—Dyspnea that occurs when the patient
is sitting up.
Pneumothorax—The presence of air or gas inside
the chest cavity.
Spirometer—An instrument that is used to test lung
capacity. It is used to screen patients with dyspnea.
Stridor—A harsh or crowing breath sound caused
by partial blockage of the patient’s upper airway.
Wheezing—A whistling or musical sound caused
by tightening of the air passages inside the patient’s
chest. Wheezing is most commonly associated
with asthma.

Resources
BOOKS

Gillespie, D. J., and E. J. Olson. ‘‘Dyspnea.’’ In Current
Diagnosis. Vol. 9. Edited by Rex B. Conn, et al.
Philadelphia: W. B. Saunders Co., 1997.

Rebecca J. Frey, PhD

Shy-Drager syndrome
Definition
Shy-Drager syndrome (SDS) is a rare condition
that causes progressive damage to the autonomic nervous system. The autonomic nervous system controls
vital involuntary body functions such as heart rate,
breathing, and intestinal, urinary, and sexual
3390

functions. The autonomic nervous system also controls skin and body temperature, and how the body
responds to stress. Shy-Drager syndrome leads to dizziness or fainting when standing up, urinary incontinence, impotence, and muscle tremors.

Description
SDS was named for neurologists Milton Shy,
M.D., from the National Institutes of Health, and
Glenn Drager, M.D., from the Baylor College of
Medicine, who first described the condition in 1960.
It typically affects those between ages 50–70. It affects
more men than women. In severe cases, the person
cannot even stand up. Symptoms can be mild as well.
Sometimes, people with mild cases are misdiagnosed
as having anxiety or hypertension.
Many nonprescription drugs, such as cold medicines and diet capsules, can trigger extremely high
blood pressure spikes in patients with SDS, even in
very low doses. Therefore, these patients are at risk for
strokes and excessive bleeding (hemorrhage) if they
take even the recommended dosage of these drugs.

Causes and symptoms
The cause of SDS is unknown. Symptoms develop
because of degeneration of certain groups of nerve
cells in the spinal cord.
Patients with SDS usually have problems with
the function of the autonomic nervous system.
Progressive degeneration may occur in other areas of
the nervous system as well. The hallmark of the syndrome is dizziness and fainting when arising or after
standing still for a long time (postural hypotension).
This is caused by low blood pressure and inadequate
blood flow to the brain. When this problem becomes
severe (for example, a blood pressure below 70/40
mmHg), it can lead to a momentary loss of consciousness. When the person faints, the blood pressure
returns to normal and the person wakes up.
Many patients also notice impotence, urinary
incontinence, dry mouth and skin, and trouble regulating body temperature because of abnormal sweating.
Since the autonomic nervous system also controls the
narrowing and widening of the iris, some patients with
SDS have vision problems, such as trouble focusing.
In later stages, problems in the autonomic nervous system lead to breathing difficulties such as
sleep apnea, loud breathing, and snoring. In advanced
stages of the disease, patients can die from irregular
heartbeat.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
While no blood test can reveal the disorder, a
careful assessment of symptoms should alert a neurologist to suspect SDS. A combination of parkinsonism
and certain autonomic problems (especially impotence, incontinence, and postural hypotension) are
clear indications of the syndrome.
Tests of the autonomic nervous system may help
diagnose the condition. In normal patients, blood
levels of norepinephrine rise when they stand up.
This doesn’t happen in people with SDS.
Norepinephrine is a hormone that helps maintain
blood pressure by triggering certain blood vessels to
constrict when blood pressure falls below normal.
Another test for the condition is the Valsalva maneuver. In this test, the patient holds his or her breath and
strains down as if having a bowel movement while the
doctor monitors blood pressure and heart rate for 10
seconds. Patients with SDS will not have the normal
increase in blood pressure and heart rate.
A variety of other tests can identify a broad range
of autonomic problems in patients with SDS. Brain
scans, however, don’t usually reveal any problems.

Treatment
Medication can relieve many of the symptoms,
especially the parkinsonism and low blood pressure.
However, typical antiparkinsonism drugs such as carbidopa-levodopa (Sinemet) should be used with caution, since they often worsen the postural low blood
pressure and may cause fainting.
Because postural hypotension is the most troublesome of the symptoms in the early years, treatments
center on relieving this problem. Patients are encouraged to eat a liberal salt diet and drink plenty of fluids.
They are advised to wear waist-high elastic hosiery and
to sleep with the head elevated at least 5 in (13 cm).
Other drug treatment includes fludrocortisone, indomethacin, nonsteroidal anti-inflammatory drugs, beta
blockers, central stimulants, and other medications.
Occasionally, a pacemaker, gastrostomy, or tracheostomy may be needed. A pacemaker is a device
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Autonomic nervous system—The part of the nervous system that controls the involuntary (apparently automatic) activities of organs, blood vessels,
glands, and many other body tissues.
Degenerative—Degenerative disorders involve
progressive impairment of both the structure and
function of part of the body.
Gastrostomy—An artificial opening into the stomach
through the abdomen to enable a patient to be fed
via a feeding tube. The procedure is given to patients
with SDS who are unable to chew or swallow.
Norepinephrine—A hormone that helps maintain
blood pressure by triggering certain blood vessels
to constrict when blood pressure falls below normal.
Sleep apnea—A sleep disorder characterized by
periods of breathing cessation lasting for 10 seconds or more.
Tracheostomy—An opening through the neck into
the trachea through which a tube may be inserted
to maintain an effective airway and help a patient
breathe.

that delivers electrical impulses to the heart to keep it
beating regularly. A gastrostomy creates an opening in
the stomach to connect a feeding tube from outside the
body. In a tracheostomy an opening is made in the
windpipe and a tube is inserted to maintain breathing.

Prognosis
While the course of the disease varies, and some
patients live for up to 20 years after the symptoms first
appear, most patients become severely disabled within
seven or eight years. It is unusual for someone to
survive more than 15 years after diagnosis.
Symptoms (especially tremor) often get worse if
the patient smokes, because of the nicotine.
Many patients develop swallowing problems
which may lead to recurrent episodes of pneumonia,
a frequent cause of death. Others experience CheyneStokes (periodic breathing). One of the most common
causes of death is pulmonary embolus. This is caused
by a blood clot in the main artery in the lung.

Prevention
Since scientists don’t know the cause of Shy-Drager
syndrome, there is no way to prevent the condition.
3391

Shy-Drager syndrome

Other symptoms of SDS do not involve the autonomic nervous system. These include parkinsonism
(muscle tremor, rigidity, and slow movements), double vision, problems controlling emotions, and wasting of muscles in the hands and feet. Eventually,
patients may have problems chewing, swallowing,
speaking, and breathing. There may be a loss of
color pigment in the iris.

Shyness

Resources
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave., St.
Paul, MN 55116. (612) 695-1940.
<http://www.aan.com>.
Association for Neuro-Metabolic Disorders. 5223
Brookfield Lane, Sylvania, OH 43560-1809. (419)
885-1497.
National Institute of Neurological Disorders and Stroke.
P.O. Box 5801, Bethesda, MD 20824. (800) 352-9424.
<http://www.ninds.nih.gov/index.htm>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.
Shy-Drager Syndrome Support Group. 2004 Howard Lane,
Austin, TX 78728. (800) 288-5582.
<http://www.shy-drager.com>.

Carol A. Turkington

Shyness
Definition
Shyness is a personality trait that produces behaviors ranging from feeling uncomfortable at a party to
an extreme fear of being watched by others while
talking on the telephone.

Description
Shyness affects people of all ages. A toddler might
run from strangers and cling to her parents. While
kindergarten is frightening for many children; some
students are anxious about the first day of school until
they graduate from college. Job interviews are stressful
for people uncomfortable talking about themselves.
For some people, feelings of self-worth are related to
their careers. Retirement may bring feelings of lower
self-esteem.
Shyness is linked to brain activity, how a person
was raised and other experiences, and the person’s
reaction to those experiences.
Social phobia
Extreme shyness is sometimes referred to as a
social phobia. Also known as social anxiety disorder,
a social phobia is a psychiatric condition defined as a
‘‘marked and persistent fear’’ of some situations. The
shy person continues to go on job interviews. Social
phobia may cause a person to remain unemployed,
3392

according to the National Mental Health
Association (NMHA). True social phobia affects
about 3% of people.
Introversion
The introvert enjoy being alone and intentionally
avoids situations like a party. The shy person wants to
be around people. However, shyness is stronger than
the desire to be sociable. The shy person is afraid to go
to the party and stays home alone.

Causes and symptoms
Temperament is related to the amygdala, the part
of the brain related to emotions and new situations.
The amygdala evaluates new situations based on
memories of past experiences. If the new situation
appears threatening, the amygdala sends a warning
signal. The amygdala in a shy person is extremely
sensitive and much more active than that of an outgoing person. The increased activity causes the person
to withdraw either physically or emotionally. This
withdrawal is known as inhibition.
The baby runs from strangers; the job applicant
laughs nervously when talking about his accomplishments. Brain activity is one component of shyness.
Environment also plays a role. If the inhibited child
has outgoing, nurturing parents, she will probably
imitate their behavior. If parents and teachers are
mocking and critical, a child may have a lifelong fear
of the first day of school. A person with that background may compare himself with others and feel they
are more capable than he is. The person embarrassed
in a job interview could become anxious in future
interviews.
At the root of shyness is a feeling of selfconsciousness. This may cause the person to blush,
tense up, or start sweating. Those are some reactions
caused when the brain signals its warning. The person
may avoid eye contact, look down, become very quiet,
or fumble over words.
Symptoms vary because there are degrees of shyness. A person might be very quiet when meeting
new people, but then become talkative when she feels
comfortable with them. The jobseeker may not be
afraid of social gatherings.
Social Phobia
Social phobia causes an extreme fear of being
humiliated or embarrassed in front of people, according to the according to the NMHA. It may be connected to low self-esteem or feelings of inferiority. The
GALE ENCYCLOPEDIA OF MEDICINE

However, social phobias have caused people to drop
out of school, avoid making friends, and keep away
from other fear-provoking situations. Phobic fears
range from speaking in pubic and dating to using public
restrooms or writing when other people are present.
According to the NMHA, phobic may feel that
everyone is looking at them, A trivial mistake is
regarded as much more serious, and blushing is painfully embarrassing. Social phobia is frequently accompanied by depression or substance abuse.

Diagnosis
In many cases, adults realize they are shy. In a
sense they have diagnosed themselves, and may take
steps to overcome their shyness. Teen-agers may also
try to remedy their situations.
Adults and youths may buy self-help books or
take classes on subjects like overcoming shyness and
assertiveness training. These classes may be taught by
counselors, psychologists, or people with experience
conquering shyness. Health-care providers often schedule these classes. They are also taught in settings
ranging from adult schools to social service agencies.
Costs will vary at these classes.
Children may not know there are treatment solutions for their shyness. Parents and educators should
be alert for symptoms of shyness in younger children.
Schools and family resource centers can provide referrals if it appears counseling want their child diagnosed.
Medical diagnosis
Based on the child’s circumstances, parents may
take the child to their health care provider. Some
insurance plans require an appointment with a doctor
before a referral to a counselor or a psychologist. The
health professional conducts an assessment and then
recommends treatment.
Children and adults may need medical treatment
for social phobia. The adult’s diagnosis also starts
with a medical exam to determine if there is a physical
cause for symptoms. If that has been ruled out, the
patient undergoes a psychiatric evaluation.
Diagnostic fees and the time allocated for evaluation vary for both shy and phobic people. Diagnosis
could span several hour-long sessions that cover an
initial evaluation, personality tests, and a meeting to
set therapy goals. Each session could cost around $90.
Insurance may cover part of the costs.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Shyness treatment concentrates on changing
behavior so the person feels more at ease in shynessprovoking situations. The person may be guided by a
self-help book or participate in individual or group
therapy.
Books and therapy generally focus on behavioral
therapy and cognitive-behavioral therapy. One method
of behavioral therapy is to expose the person to the
situation that triggers fear. This could start with
rehearsing a job interview with a friend or making
eye contact with a store clerk. Over time, the person
goes on interviews to get experience rather than to be
hired. Another person might move from eye contact to
attending an enjoyable event like a concert to become
more at ease around strangers.
Therapy also focuses on developing skills to cope
in new situation. These include taking deep breaths to
relax and practicing small talk. Cognitive-therapy
helps the person learn how thinking patterns contribute to symptoms, according to NMHA. The person is
taught techniques to change those thoughts or stop
symptoms. This association maintains this therapy is
very effective for people with social phobias.
Treatment costs very from the price of a self-help
book to the fees for therapy. Therapy sessions may be
led by a licensed marriage and family counselor, a
psychologist or psychiatrist. The cost of group therapy
is for is generally an hourly fee, with therapy planned
for a set time. The therapist might charge $80 an hour
for a social phobia group that meets three hours a
week for 16 weeks.
Treatment may include medication. Prescription
drugs like Paxil (paroxetine) are generally only prescribed to people with social anxiety disorders. Paxil is
prescribed for depression and other mood disorders.
The patient takes one tablet daily. Costs will vary, and
a 30-day order could be priced at $74 to $84.
Insurance may cover part of the costs of therapy
and medicine.

Alternative treatment
Alternative treatments for shyness focus on symptoms like tension and stress. Relaxation tapes and
CDs guide the listener through a series of actions to
relieve tension. The activity starts with deep breathing
and then the person progressively focuses on the head
and different parts of the body. The exercise may start
with the head, neck, shoulders, moving down to the
one foot and then the other. Some techniques involve
tightly tensing and then releasing each part. Another
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Shyness

phobic is not fearful in all situations and may feel
comfortable around people in most of the time.

Shyness

method is to concentrate on relaxing each part or
imagine that it becomes warm.
Another self-treatment is aromatherapy. Lavender
is a relaxing scent and is available in liquid form as an
essential oil. Stress can be relieved by adding oil to a
bath. Some people carry the oil with them. If they
become anxious, the people can dab the oil on a cotton
pad. They breathe in the lavender and feel calmer.

Prognosis
Shyness may not be a permanent. Children often
outgrow shyness. Behavioral changes and therapy can
help people feel more at ease. Furthermore, some aspects
of shyness are positive. Shy people are frequently good
listeners and are empathetic, aware of others’ feelings.

Prevention
Shyness is a personality trait related to a person’s
biology and experiences. The part of shyness related to
the brain cannot be changed. However, parents can
provide a nurturing environment that helps prevent
shyness. This will provide the child with a healthy
mental attitude that helps prevent shyness. When
faced with situations that could cause self-defeating
shyness, children will have coping skills.
According to the National Mental Health
Association, the basics of good mental health for children include:


A family that provides unconditional love not related
on accomplishments.



Nurturing self-confidence and high self-esteem by
praising children. Methods include encouraging a
child to learn a new game. The parents should set realistic goals, assure children, and smile frequently. Parents
should avoid sarcastic remarks, set realistic goals
and let children know that all people make mistakes.



Playing with other children helps the young learn how
to develop friendships and problem-solving skills.



Emphasizing that school is fun. Parents can play
school with their child to demonstrate that learning
is enjoyable. Enrolling children in preschool or children’s programs allows them to learn, be creative,
and develop social skills.



When disciplining, parents should criticize the behavior, rather than berating the child.
Shyness prevention and adults

For adults prone to shyness, the issue is related
more to treatment than prevention. Shyness for these
3394

people has probably been an issue, one that surfaces at
various times in their lives. A move, a death in the family,
job loss, and other unsettling changes could cause
emotions that include the fear associated with shyness.
In some circumstances, the person must go
through the grieving process. In other situations, the
person needs to do things that build self-confidence.
Like the child, the adult needs a support system. A
network of friends helps with encouragement and listens to the person’s concerns.
To combat the avoidance symptom caused by shyness, the person should look into enjoyable pursuits.
Recreational activities like walking groups combine
physical exercise with the opportunity to socialize.
Enrolling in a class at an adult school or community
college provides the opportunity to learn and make new
friends. Class topics range from upholstery to mystery
book discussions. Classes like these can boost confidence as a person learns a hands-on skill or discovers
that other mystery readers value her or his opinion.
Resources
PERIODICALS

Carducci, Bernardo. ‘‘Shyness: the New Solution.’’
Psychology Today January/February 2000 [cited April
5, 2005]. <http://cms.psychologytoday.com/articles/
index.php?term=PTO-20000101-000032>.
ORGANIZATIONS

American Psychological Association.750 First Street, NE,
Washington, DC 20002-4242. 800-374-2721.<http://
www.apa.org>.
National Mental Health Association. 2001 N. Beauregard
Street, 12th Floor, Alexandria, VA 22311.
703-684-7722. <http://www.nmha.org>.
Shyness Research Institute. 4201 Grant Line Road,
New Albany, IN 47150. 812-941-2295.
<http://homepages.ius.edu/Special/Shyness>.
OTHER

Jaret, Peter. ‘‘Is Shyness a Mental Disorder?’’ WebMD
Feature. April 10, 2000 [cited April 5, 2005]. <http://
my.webmd.com/content/article/13/1674_50379.htm>.
Painful Shyness in Children and Adults American
Psychological Association pamphlet. [cited April 5, 2005].
<http://www.apa.org/topics/topicshyness.html>.
Shy Child, Shy Adult. WebMD: Science, June 20, 2003:
News release, American Association for the
Advancement of Science. [cited April 5, 2005]. <http://
my.webmd.com/content/article/67/79975.htm>.
Putting Shyness in the Spotlight. Teens Health. April 2004
[cited April 1, 2005]. <http://www.kidshealth.org/teen/
your_mind/emotions/shyness.html>.

Liz Swain
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Sick sinus syndrome is a disorder of the sinus node
of the heart, which regulates heartbeat. With sick sinus
syndrome, the sinus node fails to signal properly,
resulting in changes in the heart rate.

Description
The sinus node in the heart functions as the
heart’s pacemaker, or beat regulator. In sick sinus
syndrome, patients normally will experience bradycardia, or slowed heart rate. Also, it is not uncommon
to see fluctuations between slow and rapid heart
rate (tachycardia). This makes the diagnosis and
treatment of sick sinus syndrome more complicated
than most other cardiac arrhythmias (irregular heart
beats). A sick sinus node may be responsible for
starting beats too slowly, pausing too long between
initiation of heartbeats, or not producing heartbeats
at all.

Causes and symptoms
Sick sinus syndrome may be brought on by the use
of certain drugs, but is most common in elderly
patients. Cardiac amyloidosis, a condition in which
amyloid, a kind of protein, builds up in heart tissue,
may affect the sinus node. Other conditions, such as
sarcoidosis (round bumps in the tissue surrounding the
heart and other organs), Chagas’ disease (resulting
from the bite of a bloodsucking insect) or certain
cardiac myopathies can cause fiber-like tissue to grow
around the normal sinus node, causing the node to
malfunction.
A patient may not show any symptoms of sick
sinus syndrome. In general, however, the common
symptoms are those associated with slow heart rate,
such as light-headedness, or dizziness, fatigue and
fainting. Patients may also experience confusion,
heart palpitations, angina or heart failure.

Arrhythmia—Irregular heart beat.
Atria—Plural for atrium. The atria are the upper
chambers of the heart.
Bradycardia—A heart rate slower than normal.
Electrocardiograph (ECG)—A test of a patient’s
heartbeat that involves placing leads, or detectors,
on the patient’s chest to record electrical impulses
in the heart. This test will produce a strip, or picture
record of the heart’s electrical functioning.
Myopathy—Weakness of muscle.
Pacemaker—A device implanted under the skin,
below the collarbone, to regulate heartbeat. Leads
from the device to the heart stimulate the electrical
functions of the heart. Pacemakers are often used to
control bradycardia and are usually smaller than a
silver dollar.

Treatment
If drugs are causing the problem, their withdrawal may effectively eliminate the disorder.
However, the treatment of sick sinus syndrome is
normally delayed until a patient shows symptoms.
Once treatment is indicated, most patients will
receive a pacemaker. This is a permanent treatment
involving implantation of a small device under the
skin below the collarbone. Small electrodes run from
the device to the heart; they deliver and regulate the
electrical signals that cause the heart to beat.
Patients with sick sinus syndrome should generally
receive dual chamber pacing systems to prevent
atrial fibrillation (involuntary contraction of the
muscles of the atria). Some drugs are used to treat
sick sinus syndrome, but digitalis should be used
with caution. Often the use of drugs to regulate the
heartbeat should be implemented only after the
pacemaker has been placed, since these drugs may
further worsen the slow heart rate.

Diagnosis
A slow pulse, especially one that is irregular, may
be the first indication of sick sinus syndrome.
Electrocardiography (ECGs) is a commonly used
method of detecting sick sinus syndrome. ECG monitoring for 24 hours is most useful, since with this
syndrome, heart rate may alternate between slow and
fast, and the determination of this fact can help differentiate sick sinus syndrome from other arrhythmias.
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
The reduction or elimination of certain foods and
substances, such as alcohol or caffeine, may be advised
to control heart rate. Stress reduction may also assist
with changes in rate. Homeopathic treatment can
work on a deep healing level, while acupuncture and
botanical medicine can offer supportive treatment for
symptoms.
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Sick sinus syndrome

KEY TERMS

Sick sinus syndrome

Sickle cell disease

Prognosis
Patients with sick sinus syndrome face relatively
normal lives if the disorder is controlled by a pacemaker. However, in some patients, the pacemaker
does not adequately control the fluctuations in heart
rate. Left untreated, or in severe cases, the heart could
stop beating.

Prevention
Elimination of a drug therapy which aggravates
sick sinus syndrome is the first line of treatment for
some patients. Other causes of the syndrome are not
preventable. However, proper treatment of those
underlying conditions which affect the tissues of the
heart may intervene to prevent sick sinus syndrome
from becoming a significant problem.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300.
<http://www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222.
<http://www.nhlbi.nih.gov>.

Teresa Odle

Sickle cell disease
Definition
Sickle cell disease describes a group of inherited
blood disorders characterized by chronic anemia,
painful events, and various complications due to associated tissue and organ damage.
Because sickle cell diseases are characterized by
the rapid loss of red blood cells as they enter the
circulation, they are classified as hemolytic disorders,
‘‘hemolytic’’ referring to the destruction of the cell
membrane of red blood cells resulting in the release
of hemoglobin.

Description
The most common and best-known type of sickle
cell disease is sickle cell anemia, which is also called
meniscocytosis, sicklemia, or SS disease. All types of
sickle cell disease are caused by a genetic change in
hemoglobin, the oxygen-carrying protein inside the
3396

red blood cells. The red blood cells of affected individuals contain a predominance of a structural variant
of the usual adult hemoglobin. This variant hemoglobin, called sickle hemoglobin, has a tendency to
polymerize into rod-like structures that alter the
shape of the usually flexible red blood cells. The cells
take on a shape that resembles the curved blade of the
sickle, an agricultural tool. Sickle cells have a shorter
life span than normally shaped red blood cells. This
results in chronic anemia characterized by low levels of
hemoglobin and decreased numbers of red blood cells.
Sickle cells are also less flexible and stickier than
normal red blood cells, and can become trapped in
small blood vessels preventing blood flow. This
compromises the delivery of oxygen, which can result
in pain and damage to associated tissues and organs.
Sickle cell disease presents with marked variability,
even within families.
Carriers of the sickle cell gene are said to have
sickle cell trait. Unlike sickle cell disease, sickle cell
trait does not cause health problems. In fact, sickle cell
trait is protective against malaria, a disease caused by
blood-borne parasites transmitted through mosquito
bites. According to a widely accepted theory, the
genetic mutation associated with the sickle cell trait
occurred thousands of years ago. Coincidentally, this
mutation increased the likelihood that carriers would
survive malaria infection. Survivors then passed the
mutation on to their offspring, and the trait became
established throughout areas where malaria was
common. As populations migrated, so did the sickle
cell trait. Today, approximately one in 12 African
Americans has sickle cell trait.
Worldwide, it has been estimated that one in every
250,000 babies is born annually with sickle cell disease.
Sickle cell disease primarily affects people of African,
Mediterranean, Middle Eastern, and Asian Indian
ancestry. In the United States, sickle cell disease is
most often seen in African Americans, in whom the
disease occurs in one out of every 400 births. The
disease has been described in individuals from several
different ethnic backgrounds and is also seen with
increased frequency in Latino Americans—particularly
those of Caribbean, Central American, and South
American ancestry. Approximately one in every 10001400 Latino births are affected.

Causes and symptoms
Humans normally make several types of the oxygen-carrying protein hemoglobin. An individual’s
stage in development determines whether he or she
makes primarily embryonic, fetal, or adult hemoglobins. All types of hemoglobin are made of three
GALE ENCYCLOPEDIA OF MEDICINE

Most individuals have two normal copies of the
beta globin gene, which make normal beta globin that
is incorporated into adult hemoglobin. Individuals
who have sickle cell trait (called sickle cell carriers)
have one normal beta globin gene and one sickle cell
gene. These individuals make both the usual adult
hemoglobin and sickle hemoglobin in roughly equal
proportions, so they do not experience any health
problems as a result of having the trait. Although
traces of blood in the urine and difficulty in concentrating the urine can occur, neither represents a significant health problem as a result of sickle cell trait.
Of the millions of people with sickle cell trait worldwide, a small handful of individuals have experienced
acute symptoms. In these very rare cases, individuals
were subject to very severe physical strain.
When both members of a couple are carriers of
sickle cell trait, there is a 25% chance in each pregnancy
for the baby to inherit two sickle cell genes and have
sickle cell anemia, or SS disease. Correspondingly,
there is a 50% chance the baby will have sickle cell
trait and a 25% chance that the baby will have the
usual type of hemoglobin. Other types of sickle cell
disease include SC disease, SD disease, and S/beta
thalassemia. These conditions are caused by the coinheritance of the sickle cell gene and another altered
beta globin gene. For example, one parent may have
sickle cell trait and the other parent may have hemoglobin C trait (another hemoglobin trait that does not
cause health problems). For this couple, there would be
a 25% chance of SC disease in each pregnancy.
Normal adult hemoglobin transports oxygen
from the lungs to tissues throughout the body. Sickle
hemoglobin can also transport oxygen. However, once
the oxygen is released, sickle hemoglobin tends to
polymerize (line-up) into rigid rods that alter the
shape of the red blood cell. Sickling of the red blood
cell can be triggered by low oxygen, such as occurs in
organs with slow blood flow. It can also be triggered
by cold temperatures and dehydration.
GALE ENCYCLOPEDIA OF MEDICINE

Sickle cells have a decreased life span in comparison to normal red blood cells. Normal red blood cells
survive for approximately 120 days in the bloodstream;
sickle cells last only 10–12 days. As a result, the bloodstream is chronically short of red blood cells and hemoglobin, and the affected individual develops anemia.
Sickle cells can create other complications. Due to
their shape, they do not fit well through small blood
vessels. As an aggravating factor, the outside surfaces
of sickle cells may have altered chemical properties that
increase the cells’ ‘stickiness’. These sticky sickle cells
are more likely to adhere to the inside surfaces of small
blood vessels, as well as to other blood cells. As a result
of the sickle cells’ shape and stickiness, blockages form
in small blood vessels. Such blockages prevent oxygenated blood from reaching areas where it is needed,
causing pain as well as organ and tissue damage.
The severity of symptoms cannot be predicted
based solely on the genetic inheritance. Some individuals with sickle cell disease develop health- or
life-threatening problems in infancy, but others may
have only mild symptoms throughout their lives.
Individuals may experience varying degrees of health
at different stages in the life cycle. For the most part,
this clinical variability is unpredictable, and the
reasons for the observed variability can not usually
be determined. However, certain types of sickle cell
disease (i.e. SC disease) tend to result in fewer and less
severe symptoms on average than other types of sickle
cell disease (i.e. SS disease). Some additional modifying factors are known. For example, elevated levels of
fetal hemoglobin in a child or adult can decrease the
quantity and severity of some symptoms and complications. Fetal hemoglobin is a normally occurring
hemoglobin that usually decreases from over 90% of
the total hemoglobin to under 1% during the first year
of life. This change is genetically determined, although
some individuals may experience elevated levels of
fetal hemoglobin due to variation in the genes that
control fetal hemoglobin production. Such individuals
often experience a reduction in their symptoms and
complications due to the ability of fetal hemoglobin to
prevent the polymerization of sickle hemoglobin,
which leads to sickling of the red blood cell.
There are several symptoms that warrant immediate medical attention, including the following:


signs of infection (fever greater than >1018F or
38.38C, coughs frequently or breathing trouble, unusual crankiness, feeding difficulties)



signs of severe anemia (pale skin or lips, yellowing of
the skin or eyes, very tired, very weak)



signs indicating possible dehydration (vomiting, diarrhea, fewer wet diapers)
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Sickle cell disease

components: heme, alpha (or alpha-like) globin, and
beta (or beta-like) globin. Sickle hemoglobin is the
result of a genetic change in the beta globin component of normal adult hemoglobin. The beta globin
gene is located on chromosome 11. The sickle cell
form of the beta globin gene results from the substitution of a single DNA nucleotide, or genetic buildingblock. The change from adenine to thymine at codon
(position) 6 of the beta globin gene leads to insertion of
the amino acid valine–instead of glutamic acid–at this
same position in the beta globin protein. As a result of
this change, sickle hemoglobin has unique properties
in comparison to the usual type of adult hemoglobin.

Sickle cell disease



other signs (pain or swelling in the abdomen, swollen
hands or feet, screams when touched)

These can be signs of various complications that
occur in sickle cell disease.
Infections and effects on the spleen
Children with sickle cell disease who are under age
three are particularly prone to life-threatening bacterial infections. Streptococcus pneumoniae is the most
common offending bacteria, and invasive infection
from this organism leads to death in 15% of cases.
The spleen, an organ that helps to fight bacterial infections, is particularly vulnerable to the effects of sickling. Sickle cells can impede blood flow through the
spleen, causing organ damage, which usually results in
loss of spleen function by late childhood. The spleen
can also become enlarged due to blockages and/or
increased activity of the spleen. Rapid enlargement
of the spleen may be a sign of another complication
called splenic sequestration, which occurs mostly
in young children and can be life-threatening.
Widespread sickling in the spleen prevents adequate
blood flow from the organ, removing increasing
volumes of blood from the circulation and leading to
accompanying signs of severe anemia.
Painful events
Painful events, also known as vaso-occlusive events,
are a hallmark symptom of sickle cell disease. The
frequency and duration of the pain can vary tremendously from person to person and over an individual’s
life cycle. Painful events are the most common cause of
hospitalizations in sickle cell disease. However, only a
small portion of individuals with sickle cell disease
experience frequent and severe painful events. Most
painful events can be managed at home. Pain results
when small blood vessel blockages prevent oxygen from
reaching tissues. Pain can affect any area of the body,
although the extremities, chest, abdomen, and bones
are frequently affected sites. There is some evidence that
cold temperatures or infection can trigger a painful
event, but most events occur for unknown reasons.
The hand-foot syndrome, or dactylitis , is a particular
type of painful event. Most common in toddlers, dactylitis results in pain and swelling in the hands and feet,
sometimes accompanied by a fever.
Anemia
Sickle cells have a high turnover rate leading to a
deficit of red blood cells in the bloodstream. Common
symptoms of anemia include fatigue, paleness, and a
shortness of breath. A particularly severe form of
3398

anemia—aplastic anemia—occurs following infection
with parvovirus. Parvovirus causes extensive destruction of the bone marrow, bringing production of new
red blood cells to a halt. Bone marrow production
resumes after seven to 10 days; however, given the
short lives of sickle cells, even a brief shut-down in
red blood cell production can cause a rapid decline in
hemoglobin concentrations.
Delayed growth
The energy demands of the bone marrow for red
blood cell production compete with the demands of a
growing body. Children with sickle cell anemia may
have delayed growth and reach puberty at a later age
than normal. By early adulthood, they catch up on
growth and attain normal height; however, weight
typically remains below average.
Stroke
Children with sickle cell disease have a significantly
elevated risk of having a stroke, which can be one of the
most concerning complications of sickle cell disease.
Approximately 11% of individuals with sickle cell disease will have a recognizable stroke by the age of 20.
Magnetic resonance imaging studies have found that
17% of children with sickle cell anemia have evidence
of a previous stroke or clinically ‘silent’ stroke-like
events called transient ischemic events. Stroke in sickle
cell disease is usually caused by a blockage of a blood
vessel, but about one fourth of the time may be caused
by a hemorrhage (or rupture) of a blood vessel.
Strokes result in compromised delivery of oxygen
to an area of the brain. The consequences of stroke can
range from life-threatening, to severe physical or cognitive impairments, to apparent or subtle learning disabilities, to undetectable effects. Common stroke
symptoms include weakness or numbness that affects
one side of the body, sudden behavioral changes, loss
of vision, confusion, loss of speech or the ability to
understand spoken words, dizziness, headache, seizures, vomiting, or even coma.
Approximately two-thirds of the children who
have a stroke will have at least one more. Transfusions
have been shown to decrease the incidence of a second
stroke. A recent study showed that children at highest
risk to experience a first stroke were 10 times more likely
to stroke if untreated when compared to high-risk
children treated with chronic blood transfusion therapy.
High-risk children were identified using transcranial
doppler ultrasound technology to detect individuals
with increased blood flow speeds due to constricted
intracranial blood vessels.
GALE ENCYCLOPEDIA OF MEDICINE

Jaundice and gallstones

A scanning electron microscopy (SEM) scan of red blood
cells taken from a person with sickle cell anemia. The blood
cells at the bottom are normal; the diseased, sickle-shaped
cells appear at the top. (Photograph by Dr. Gopal Murti, Photo
Researchers, Inc. Reproduced by permission.)

As of 2003, researchers are investigating various
techniques for helping children with memory loss
related to strokes caused by sickle cell disease.
Acute chest syndrome
Acute chest syndrome (ACS) is a leading cause of
death for individuals with sickle cell disease, and recurrent attacks can lead to permanent lung damage.
Therefore rapid diagnosis and treatment is of great
importance. ACS can occur at any age and is similar
but distinct from pneumonia. Affected persons may
experience fever, cough, chest pain, and shortness of
breath. ACS seems to have multiple causes including
infection, sickling in the small blood vessels of the lungs,
fat embolisms to the lungs, or a combination of factors.
Priapism
Males with sickle cell anemia may experience
priapism, a condition characterized by a persistent
and painful erection of the penis. Due to blood vessel
blockage by sickle cells, blood is trapped in the tissue
of the penis. Priapism may be short in duration or it
may be prolonged. Priapism can be triggered by low
oxygen (hypoxemia), alcohol consumption, or sexual
intercourse. Since priapism can be extremely painful
and result in damage to this tissue causing impotence,
rapid treatment is essential.
Kidney disease
The environment in the kidney is particularly
prone to damage from sickle cells. Signs of kidney
damage can include blood in the urine, incontinence,
and enlarged kidneys. Adults with sickle cell disease
GALE ENCYCLOPEDIA OF MEDICINE

Jaundice is indicated by a yellow tone in the skin
and eyes, and alone it is not a health concern. Jaundice
may occur if bilirubin levels increase, which can occur
with high levels of red blood cell destruction. Bilirubin
is the final product of hemoglobin degradation, and is
typically removed from the bloodstream by the liver.
Therefore, jaundice can also be a sign of a poorly
functioning liver, which may also be evidenced by an
enlarged liver. Increased bilirubin also leads to
increased chance for gallstones in children with sickle
cell disease. Treatment, which may include removal of
the gall bladder, may be selected if the gallstones start
causing symptoms.
Retinopathy
The blood vessels that supply oxygen to the
retina—the tissue at the back of the eye—may be
blocked by sickle cells, leading to a condition called
retinopathy. This is one of the only complications that
is actually more common in SC disease as compared to
SS disease. Retinopathy can be identified through
regular ophthalmology evaluations and effectively
treated in order to avoid damage to vision.
Joint problems
Avascular necrosis of the hip and shoulder joints,
in which bone damage occurs due to compromised
blood flow due to sickling, can occur later in childhood. This complication can affect an individual’s
physical abilities and result in substantial pain.

Diagnosis
Inheritance of sickle cell disease or trait cannot be
prevented, but it may be predicted. Screening is recommended for individuals in high-risk populations. In
the United States, African Americans and Latino
Americans have the highest risk of having the disease
or trait. Sickle cell is also common among individuals
of Mediterranean, Middle Eastern, and Eastern
Indian descent.
A complete blood count (CBC) will describe several aspects of an individual’s blood cells. A person
with sickle cell disease will have a lower than normal
hemoglobin level, together with other characteristic
red blood cell abnormalities. A hemoglobin electrophoresis is a test that can help identify the types and
3399

Sickle cell disease

often experience insufficient functioning of the kidneys, which can progress to kidney failure in a small
percentage of adults with sickle cell disease.

Sickle cell disease

quantities of hemoglobin made by an individual. This
test uses an electric field applied across a slab of gellike material. Hemoglobins migrate through this gel at
various rates and to specific locations, depending on
their size, shape, and electrical charge. Although sickle
hemoglobin (Hb S) and regular adult hemoglobin
(called Hb A) differ by only one amino acid, they can
be clearly separated using hemoglobin electrophoresis.
Isoelectric focusing and high-performance liquid
chromatography (HPLC) use similar principles to
separate hemoglobins and can be used instead of or
in various combinations with hemoglobin electrophoresis to determine the types of hemoglobin present.
Another test called the sickledex can help confirm
the presence of sickle hemoglobin, although this test
cannot provide accurate or reliable diagnosis when
used alone. When Hb S is present, but there is an
absence or only a trace of Hb A, sickle cell anemia is
a likely diagnosis. Additional beta globin DNA testing,
which looks directly at the beta globin gene, can be
performed to help confirm the diagnosis and establish
the exact genetic type of sickle cell disease. CBC and
hemoglobin electrophoresis are also typically used to
diagnose sickle cell trait and various other types of
beta globin traits.
Diagnosis of sickle cell disease can occur under
various circumstances. If an individual has symptoms
that are suggestive of this diagnosis, the abovedescribed screening tests can be performed followed
by DNA testing, if indicated. Screening at birth using
HPLC or a related technique offers the opportunity
for early intervention. More than 40 states include
sickle cell screening as part of the usual battery of
blood tests done for newborns. This allows for early
identification and treatment. Hemoglobin trait screening is recommended for any individual of a high-risk
ethnic background who may be considering having
children. When both members of a couple are found
to have sickle cell trait, or other related hemoglobin
traits, they can receive genetic counseling regarding the
risk of sickle cell disease in their future children and
various testing options.
Sickle cell disease can be identified before birth
through the use of prenatal diagnosis. Chorionic villus
sampling (CVS) can be offered as early as 10 weeks of
pregnancy and involves removing a sample of the
placenta made by the baby and testing the cells. CVS
carries a risk of causing a miscarriage that is between
one-half to one percent.
Amniocentesis is generally offered between 15 and
22 weeks of pregnancy, but can sometimes be offered
earlier. Two to three tablespoons of the fluid surrounding the baby is removed. This fluid contains
3400

fetal cells that can be tested. This test carries a risk of
causing a miscarriage, which is not greater than one
percent. Pregnant woman and couples may choose
prenatal testing in order to prepare for the birth of a
baby that may have sickle cell disease. Alternately,
knowing the diagnosis during pregnancy allows for
the option of pregnancy termination.
Preimplantation genetic diagnosis (PGD) is a
relatively new technique that involves in-vitro fertilization followed by genetic testing of one cell from each
developing embryo. Only the embryos unaffected by
sickle cell disease are transferred back into the uterus.
PGD is currently available on a research basis only,
and is relatively expensive.

Treatment
There are several practices intended to prevent
some of the symptoms and complications of sickle
cell disease. These include preventative antibiotics,
good hydration, immunizations, and access to comprehensive care. Maintaining good health through
adequate nutrition, avoiding stresses and infection,
and getting proper rest is also important. Following
these guidelines is intended to improve the health of
individuals with sickle cell disease.
Penicillin
Infants are typically started on a course of penicillin that extends from infancy to age six. Use of
this antibiotic is meant to ward off potentially fatal
infections. Infections at any age are treated aggressively with antibiotics. Vaccines for common infections, such as pneumococcal pneumonia, are also
recommended.
Pain management
Pain is one of the primary symptoms of sickle cell
anemia, and controlling it is an important concern.
The methods necessary for pain control are based on
individual factors. Some people can gain adequate
pain control through over-the-counter oral painkillers
(analgesics). Other individuals, or painful events, may
require stronger methods that can include administration of narcotics. Alternative therapies may be useful
in avoiding or controlling pain, including relaxation,
hydration, avoiding extremes of temperature, and the
application of local warmth.
Blood transfusions
Blood transfusions are not usually given on a
regular basis but are used to treat individuals with
GALE ENCYCLOPEDIA OF MEDICINE

Regular blood transfusions have the potential to
decrease formation of hemoglobin S, and reduce associated symptoms. However, there are limitations and
risks associated with regular blood transfusions,
including the risk of blood-borne infection and sensitization to proteins in the transfused blood that can
make future transfusions very difficult. Most importantly, chronic blood transfusions can lead to iron
overload. The body tends to store excess iron, such
as that received through transfusions, in various
organs. Over time, this iron storage can cause damage
to various tissues and organs, such as the heart and
endocrine organs.
Some of this damage can be prevented by the
administration of a medication called desferoxamine
that helps the body to eliminate excess iron through
the urine. Alternately, some individuals receive a new,
non-standard treatment called erythrocytapheresis.
This involves the automated removal of sickle cells
and is used in conjunction with a reduced number of
regular transfusions. This treatment helps to reduce
iron overload.
Hydroxyurea
Emphasis is being placed on developing drugs that
treat sickle cell anemia directly. The most promising of
these drugs in the late 1990s is hydroxyurea, a drug
that was originally designed for anticancer treatment.
Hydroxyurea has been shown to reduce the frequency
of painful crises and acute chest syndrome in adults,
and to lessen the need for blood transfusions.
Hydroxyurea seems to work by inducing a higher
production of fetal hemoglobin. The major side effects
of the drug include decreased production of platelets,
red blood cells, and certain white blood cells. The
effects of long-term hydroxyurea treatment are
unknown; however, a nine-year follow-up study of
299 adults with frequent painful crises reported in
2003 that taking hydroxyurea was associated with a
40% reduction in mortality.
Bone marrow transplantation
Bone marrow transplantation has been shown to
cure sickle cell anemia in some cases. This treatment is
reserved primarily for severely affected children with a
healthy donor whose marrow proteins match those of
the recipient, namely a brother or sister who has
GALE ENCYCLOPEDIA OF MEDICINE

inherited the same tissue type. Indications for a bone
marrow transplant are stroke, recurrent acute chest
syndrome, and chronic unrelieved pain.
Bone marrow transplantations tend to be the most
successful in children; adults have a higher rate of
transplant rejection and other complications. There is
approximately a 10% fatality rate associated with bone
marrow transplants done for sickle cell disease.
Survivors face potential long-term complications, such
as chronic graft-versus-host disease (an immunemediated attack by the donor marrow against the recipient’s tissues), infertility, and development of some
forms of cancer. A relatively recent advance in transplantation involves the use of donor stem cells obtained
from cord blood, the blood from the placenta that is
otherwise discarded following the birth of a new baby.
Cord blood cells, as opposed to fully mature bone
marrow cells, appear to be less likely to result in graftversus-host disease in the recipient. This increases the
safety and efficacy of the transplant procedure.
Surgery
Certain surgical interventions are utilized in the
treatment of specific sickle cell-related complications.
Removal of a dysfunctioning gallbladder or spleen can
often lead to improvements in health. Investigations
are currently underway to establish the efficacy of hip
coring surgery, in which a portion of affected bone
is removed to treat avascular necrosis of the hip.
The hope is that this may provide an effective treatment to alleviate some pain and restore function in the
affected hip.
Gene research
Replacing the gene that produces the defective
hemoglobin in sickle cell disease patients with one
that makes normal hemoglobin may be a possible
treatment due to recent research. According to a
1998 report in Science, researchers studied the blood
cells from people who carry the sickle cell gene. By
using an enzyme called a ribosome, the study was able
to alter sickle cells into normal cells. The ribosome cut
out the mutated instructions in the cells’ genetic pattern and replaced them with the correct instructions.
Researchers hope that this will allow the cells to make
normal hemoglobin— leading to the ultimate treatment for those with sickle cell disease.
In late 2001, genetic scientists reported that they
had designed a gene that might lead to a future treatment of sickle cell anemia. Although the gene had not
been tested in humans, early results showed that the
injected gene protected cells from sickling. As of 2003,
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Sickle cell disease

frequent and severe painful events, severe anemia, and
other emergencies. In some cases blood transfusions are
given as a preventative measure, for example to treat
spleen enlargement or prevent a second stroke (or a first
stroke in an individual shown to be at high risk).

Sickle cell disease

KEY TERMS
Amino acid—Organic compounds that form the
building blocks of protein. There are 20 types of
amino acids (eight are ‘‘essential amino acids’’
which the body cannot make and must therefore be
obtained from food).
Anemia—A blood condition in which the level of
hemoglobin or the number of red blood cells falls
below normal values. Common symptoms include
paleness, fatigue, and shortness of breath.
Bilirubin—A yellow pigment that is the end result of
hemoglobin breakdown. This pigment is metabolized in the liver and excreted from the body through
the bile. Bloodstream levels are normally low; however, extensive red cell destruction leads to excessive bilirubin formation and jaundice.
Bone marrow—A spongy tissue located in the hollow centers of certain bones, such as the skull and
hip bones. Bone marrow is the site of blood cell
generation.
Bone marrow transplantation—A medical procedure used to treat some diseases that arise from defective blood cell formation in the bone marrow. Healthy
bone marrow is extracted from a donor to replace the
marrow in an ailing individual. Proteins on the surface
of bone marrow cells must be identical or very closely
matched between a donor and the recipient.
Globin—One of the component protein molecules
found in hemoglobin. Normal adult hemoglobin has
a pair each of alpha-globin and beta-globin molecules.
Heme—The iron-containing molecule in hemoglobin that serves as the site for oxygen binding.
Hemoglobin—Protein-iron compound in the blood
that carries oxygen to the cells and carries carbon
dioxide away from the cells.
Hemoglobin A—Normal adult hemoglobin that contains a heme molecule, two alpha-globin molecules,
and two beta-globin molecules.
Hemoglobin electrophoresis—A laboratory test that
separates molecules based on their size, shape, or
electrical charge.
Hemoglobin S—Hemoglobin produced in association with the sickle cell trait; the beta-globin molecules of hemoglobin S are defective.
Hemolytic—Referring to the destruction of the cell
membranes of red blood cells, resulting in the
release of hemoglobin from the damaged cell.

3402

Hydroxyurea—A drug that has been shown to
induce production of fetal hemoglobin. Fetal hemoglobin has a pair of gamma-globin molecules in
place of the typical beta-globins of adult hemoglobin. Higher-than-normal levels of fetal hemoglobin
can prevent sickling from occurring.
Impotence—The inability to have a penile erection,
which can be due to tissue damage resulting from
sickling within the penis (priapism).
Iron overload—A side effect of frequent blood transfusions in which the body accumulates abnormally
high levels of iron. Iron deposits can form in organs,
particularly the heart, and cause life-threatening
damage.
Jaundice—Yellowing of the skin or eyes due to
excess of bilirubin in the blood.
Magnetic resonance imaging (MRI)—A technique
that employs magnetic fields and radio waves to
create detailed images of internal body structures
and organs, including the brain.
Meniscocytosis—Another word for sickle cell disease.
Mutation—A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted
to offspring.
Narcotics—Strong, prescription medication that can
be effective in treating pain, but have the potential to
be habit-forming if their use is not supervised correctly.
Nucleic acid—The cellular molecules DNA and
RNA that act as coded instructions for the production
of proteins and are copied for transmission of inherited traits.
Ophthalmology—The medical specialty of vision
and the eye.
Placenta—The organ responsible for oxygen and
nutrition exchange between a pregnant mother and
her developing baby.
Red blood cell—Hemoglobin-containing blood cells
that transport oxygen from the lungs to tissues. In the
tissues, the red blood cells exchange their oxygen for
carbon dioxide, which is brought back to the lungs to
be exhaled.
Screening—Process through which carriers of a trait
may be identified within a population.
Sickle cell—A red blood cell that has assumed an
elongated shape due to the presence of hemoglobin S.

GALE ENCYCLOPEDIA OF MEDICINE

Psychosocial support
As in any lifelong, chronic disease, comprehensive
care is important. Assistance with the emotional,
social, family-planning, economic, vocational, and
other consequences of sickle cell disease can enable
affected individuals to better access and benefit from
their medical care.

Prognosis
Sickle cell disease is characteristically variable
between and within affected individuals. Predicting
the course of the disorder based solely on genes is
not possible. Several factors aside from genetic inheritance determine the prognosis for affected individuals,
including the frequency, severity, and nature of specific complications in any given individual. The availability and access of comprehensive medical care also
plays an important role in preventing and treating
serious, acute complications, which cause the majority
of sickle cell-related deaths. For those individuals who
do not experience such acute events, life expectancy is
probably substantially greater than the average for all
people with sickle cell disease. The impact of recent
medical advances supports the hypothesis that current
life expectancies may be significantly greater than
those estimated in the early 1990s. At that time, individuals with SS disease lived to the early- to mid-40s,
and those with SC disease lived into the upper 50s on
average. As of 2003, the life expectancy of persons with
SS is over 50. With early detection and comprehensive
medical care, most people with sickle cell disease are in
fairly good health most of the time. Most individuals
can be expected to live well into adulthood, enjoying
an improved quality of life including the ability to
choose a variety of education, career, and family-planning options for themselves.

Hemoglobinopathies.’’ Section 18, Chapter 251 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Davies, S. C., and A. Gilmore. ‘‘The Role of Hydroxyurea in
the Management of Sickle Cell Disease.’’ Blood Reviews
17 (June 2003): 99–109.
Egbert Maikler, Virginia, et al.‘‘Children’s and Adolescents’
Use of Diaries for Sickle Cell Pain.’’ Journal of the
Society of Pediatric Nurses 6, no. 4 (October –
December 2001): 161 – 169.
Harris, Leslie. ‘‘Living Well with Sickle Cell.’’ Essence
September 1999: 58.
Nienhuis,A. W., H. Hanawa, N. Sawai, et al. ‘‘Development
of Gene Therapy for Hemoglobin Disorders.’’ Annals
of the New York Academy of Science 996 (May 2003):
101–111.
Seppa, N. ‘‘Gene Therapy for Sickle-cell Disease?’’ Science
News 160, no. 24 (December 15, 2001): 372.
Steinberg, M. H., F. Barton, O. Castro, et al. ‘‘Effect of
Hydroxyurea on Mortality and Morbidity in Adult
Sickle Cell Anemia: Risks and Benefits up to 9 Years of
Treatment.’’ Journal of the American Medical
Association 289 (April 2, 2003): 1645–1651.
Winrow, N., and E. R. Melhem. ‘‘Sickle Cell Disease and
Stroke in a Pediatric Population. Evidence-Based
Diagnostic Evaluation.’’ Neuroimaging Clinics of North
America 13 (May 2003): 185–196.
Yerys, B. E., D. A. White, C. F. Salorio, et al. ‘‘Memory
Strategy Training in Children with Cerebral Infarcts
Related to Sickle Cell Disease.’’ Journal of Pediatric
Hematology and Oncology 25 (June 2003): 495–498.
ORGANIZATIONS

Mayo Foundation for Medical Education and Research.
<http://www.mayohealth.org>.
Sickle Cell Disease Association of America. 200 Corporate
Point, Suite 495, Culver City, CA 90230-7633. (310)
216-6363. (800) 421-8453.
<http://sicklecelldisease.org/>.
Sickle Cell Disease Program, Division of Blood Diseases and
Resources. National Heart, Lung, and Blood Institute.
II Rockledge Centre, 6701 Rockledge Dr. MSC 7950,
Bethesda, MD 20892-7950. (301) 435-0055.

Jennifer Bojanowski, MS, CGC
Rebecca J. Frey, PhD

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Anemias Caused by Excessive Hemolysis: Sickle Cell
Diseases.’’ Section 11, Chapter 127 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Pregnancy Complicated by Disease:
GALE ENCYCLOPEDIA OF MEDICINE

Sideroblastic anemia
Definition
Sideroblastic anemia is a term used to describe a
group of rare blood disorders characterized by the
3403

Sideroblastic anemia

experiments in gene therapy for sickle cell disease have
been carried out in mice, using lentiviral vectors to
transfer the corrective gene into the mouse’s stem
cells. This technique, however, has not yet been
attempted in human subjects as of late 2003.

Sigmoidoscopy

bone marrow’s inability to manufacture normal red
blood cells.

Description
Named for the Greek words for iron and germ,
sideroblastic anemia is one of the principal types of
iron-utilization anemia. Abnormal, iron-saturated red
cells are present in the blood of people who have this
disease. Although the iron circulates normally from
the plasma to the bone marrow, where new red blood
cells are created, it is not properly incorporated into
new red blood cells.
Sideroblastic anemia can be inherited, but the
disease is usually acquired as a result of illness or
exposure to toxic substances.
Sideroblastic anemia is a disease of adults.

Causes and symptoms
The cause of sideroblastic anemia cannot always
be identified. Drug toxicity, alcohol abuse, and lead
poisoning are common causes of this condition.
Sideroblastic anemia is also associated with:


leukemia



lymphoma (cancer of the lymph glands)



myeloma (cancer of the bone marrow)



rheumatoid arthritis, and other inflammatory
diseases

Symptoms of sideroblastic anemia are the same as
symptoms of the disease that causes the condition, as
well as anemia
Complications

Diagnosis
Blood tests are used to examine the appearance
and other characteristics of red cells and to measure
the amount of iron in the blood. Bone marrow biopsy is
also used.

Treatment
Acquired sideroblastic anemia may be cured when
the condition that causes it is treated or removed.
If the cause of a patient’s anemia cannot be determined, blood transfusions may be necessary.
Medications are prescribed to stimulate excretion or
excess iron that accumulates as a result of these
transfusions.
In rare instances, treatment with oral pyridoxine
(a B-complex vitamin) benefits patients whose sideroblastic anemia was present at birth. This treatment
improves the condition of some patients but does not
cure the anemia.

Prognosis
Sideroblastic anemia of unknown origin may lead
to leukemia. It may take as long as 10 years for this
disease progression to take place.
Resources
ORGANIZATIONS

Leukemia Society of America, Inc. 600 Third Ave., New
York, NY 10016. (800) 955 4572. <http://
www.leukemia.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Possible complications of sideroblastic anemia
include:


congestive heart failure



diabetes mellitus



enlargement of the liver and spleen



formation of liver nodules and scar tissue



irregular heartbeat



recurring inflammation of the sac that surrounds the
heart



secondary hypopituitarism (dwarfism)



skin darkening



underactivity of the thyroid gland

3404

Maureen Haggerty

SIDS see Sudden infant death syndrome

Sigmoidoscopy
Definition
Sigmoidoscopy is a procedure by which a doctor
inserts either a short and rigid or slightly longer and
flexible fiber-optic tube into the rectum to examine the
lower portion of the large intestine (or bowel).
GALE ENCYCLOPEDIA OF MEDICINE

Sigmoidoscopy is used most often in screening for
colorectal cancer or to determine the cause of rectal
bleeding. It is also used for the diagnosis of inflammatory bowel disease and other benign diseases of the
lower intestine.
Cancer of the rectum and colon is the second most
common cancer in the United States, and claims the
lives of approximately 56,000 people annually. As a
result, The American Cancer Society recommends
that people age 50 and over be screened for colorectal
cancer every five years. The screening includes a flexible
sigmoidoscopy. Screening at an earlier age should be
done on patients who have a family history of colon or
rectal cancer, or small growths in the colon (polyps).
Individuals with inflammatory bowel disease
(Crohn’s colitis or ulcerative colitis) are at increased
risk for colorectal cancer and should begin their
screenings at a younger age, and be screened more
frequently. Many doctors screen such patients more
often than every three to five years. Those with ulcerative colitis should be screened beginning 10 years after
the onset of disease; those with Crohn’s colitis beginning 15 years after the onset of disease.
Some doctors prefer to do this screening with a
colonoscope, which allows them to see the entire colon
(certain patients, such as those with Crohn’s colitis or
ulcerative colitis, must be screened with a colonoscope). However, compared with sigmoidoscopy, colonoscopy is a longer process, causes more discomfort,
and is more costly.
Studies have indicated that about one-fourth of all
precancerous or small cancerous growths in the colorectal region can be seen with a rigid sigmoidoscope.
The longer, flexible version, which is the primary type
of sigmoidoscope used in the screening process, can
detect more than one-half of all growths in this region.
This examination is usually performed in combination
with a fecal occult blood test, in an effort to increase
detection of polyps and cancers that lie beyond the
scope’s reach.

Precautions
Sigmoidoscopy can usually be conducted in a
doctor’s office or a health clinic. However, some individuals should have the procedure done in a hospital
day surgery facility. These include patients with rectal
bleeding, and patients whose blood does not clot well
(possibly as a result of blood-thinning medications).
The exam is not always adequate. A 2004 study
reported that among older patients and women,
GALE ENCYCLOPEDIA OF MEDICINE

sigmoidoscopy is not always effective, particularly
because insertion depth is not adequate. For unknown
reasons, this is almost twice as true for women as
for men.

Description
Most sigmoidoscopy is done with a flexible fiberoptic tube. The tube contains a light source and a
camera lens. The doctor moves the sigmoidoscope up
beyond the rectum (the first 1 ft/30 cm of the colon),
examining the interior walls of the rectum. If a 2 ft/60
cm scope is used, the next portion of the colon can also
be examined for any irregularities.
The procedure takes 20 to 30 minutes, during
which time the patient will remain awake. Light sedation may be given to some patients. There is some
discomfort (usually bloating and cramping) because
air is injected into the bowel to widen the passage for
the sigmoidoscope. Pain is rare except in individuals
with active inflammatory bowel disease.
In a colorectal cancer screening, the doctor is
looking for polyps or tumors. Studies have shown
that over time, many polyps develop into cancerous
lesions and tumors. Using instruments threaded
through the fiber-optic tube, cancerous or precancerous polyps can either be removed or biopsied during
the sigmoidoscopy. People who have cancerous polyps
removed can be referred for full colonoscopy, or more
frequent sigmoidoscopy, as necessary.
The doctor may also look for signs of ulcerative
colitis, which include a loss of blood flow to the lining
of the bowel, a thickening of the lining, and sometimes
a discharge of blood and pus mixed with stool. The
doctor can also look for Crohn’s disease, which often
appears as shallow or deep ulcerations, or erosions
and fissures in the lining of the colon. In many cases,
these signs appear in the first few centimeters of the
colon above the rectum, and it is not necessary to do a
full colonoscopic exam.
Private insurance plans often cover the cost of
sigmoidoscopy for screening in healthy individuals
over 50, or for diagnostic purposes. Medicare covers
the cost for diagnostic exams, and may cover the costs
for screening exams.

Preparation
The purpose of preparation for sigmoidoscopy is
to clean the lower bowel of stool so that the doctor can
see the lining. Many patients are required to consume
only clear liquids on the day before the test, and to
take two enemas on the morning of the procedure. The
3405

Sigmoidoscopy

Purpose

Sigmoidoscopy
Sigmoidoscopy is a procedure most often used in screening for colorectal cancer and as a test in diagnosis of possible
inflammatory bowel disease. As illustrated above, the physician can view the rectum and colon through a sigmoidoscope, a 12
inch (30 cm) or 24 inch (60 cm) flexible fiber-optic tube which contains a light source and a lens. (Illustration by Electronic
Illustrators Group.)

bowel is cleaner, however, if patients also take an oral
laxative preparation of 1.5 oz phospho-soda the evening before the sigmoidoscopy.
Certain medications should be avoided for a week
before having a sigmoidoscopy. These include:


aspirin, or products containing aspirin



ibuprofen products (Nuprin, Advil, or Motrin)



iron or vitamins containing iron

Although most prescription medication can be
taken as usual, patients should check with their doctor
in advance.

Risks
There is a slight risk of bleeding from the procedure. This risk is heightened in individuals whose
blood does not clot well, either due to disease or
medication, and in those with active inflammatory
bowel disease. The most serious complication of sigmoidoscopy is bowel perforation (tear). This complication is very rare, however, occurring only about
once in every 7,500 procedures.

Normal results
A normal exam shows a smooth bowel wall with
no evidence of inflammation, polyps or tumors.

Aftercare
Patients may feel mild cramping after the procedure that will improve after passing gas. Patients can
resume their normal activities almost immediately.
3406

Abnormal results
For a cancer screening sigmoidoscopy, an abnormal result involves one or more noncancerous or
GALE ENCYCLOPEDIA OF MEDICINE

Biopsy—A procedure where a piece of tissue is
removed from a patient for diagnostic testing.
Colorectal cancer—Cancer of the large intestine,
or colon, including the rectum (the last 16 in of the
large intestine before the anus).
Inflammatory bowel disease—Ulcerative colitis or
Crohn’s colitis; chronic conditions characterized
by periods of diarrhea, bloating, abdominal
cramps, and pain, sometimes accompanied by
weight loss and malnutrition because of the inability to absorb nutrients.

‘‘Women are Twice as Likely as Men to Have an Inadequate
Signoidoscopy Examination.’’ Doctor February 5,
2004: 13.
OTHER

‘‘Diagnostic Tests.’’ The National Digestive Diseases
Information Clearing house (National Institutes of
Health). July 5, 2001. <http://www.niddk.nih.gov/
health/digest/pubs/diagtest/index.htm>.
‘‘Overview: Colon and Rectum Cancer.’’ The American
Cancer Society. Jan. 20, 2005. http://www.cancer.org/
docroot/CRI/content/CRI_2_2_1X_How_Many_
People_Get_Colorectal_Cancer.asp?sitearea=.

Jon H. Zonderman
Teresa G. Odle

Polyp—A small growth that can be precancerous
when it appears in the colon.

precancerous polyps or tumors. Patients showing
polyps have an increased risk of developing colorectal
cancer in the future.
Small polyps can be completely removed. Larger
polyps or tumors usually require the doctor to remove
a portion of the growth for diagnostic testing.
Depending on the test results, the patient is then
scheduled to have the growth removed surgically,
either as an urgent matter if it is cancerous, or as an
elective surgery within a few months if it is
noncancerous.
In a diagnostic sigmoidoscopy, an abnormal
result shows signs of active inflammatory bowel disease, either a thickening of the intestinal lining consistent with ulcerative colitis, or ulcerations or fissures
consistent with Crohn’s disease.
Sigmoidoscopy is a procedure most often used in
screening for colorectal cancer and as a test in diagnosis of possible inflammatory bowel disease. As illustrated above, the physician can view the rectum and
colon through a sigmoidoscope, a 12 inch (30 cm) or
24 inch (60 cm) flexible fiber-optic tube which contains
a light source and a lens.
Resources
PERIODICALS

Johnson, Brett Andrew. ‘‘Flexible Sigmoidoscopy:
Screening for Colorectal Cancer.’’ American Family
Physician March 15, 1999: 1537–46.
Manoucheri, Manoucher, et al. ‘‘Bowel Preparations for
Flexible Sigmoidoscopy: Which Method Yields the Best
Results?’’ The Journal of Family Practice 48, no. 4
(April, 1999): 272–4.
GALE ENCYCLOPEDIA OF MEDICINE

Sildenafil citrate
Definition
Sildenafil citrate (Viagra) is a medication used to
treat erectile dysfunction (ED), or impotence, in men.

Purpose
Labeled use
Viagra treats erectile dysfunction, the inability to
achieve and/or maintain an erection of the penis that is
adequate for sexual intercourse. Ten to fifteen million
men in the United States suffer from ED, and by age
65, up to 25% of men have experienced impotence
problems. Erectile dysfunction can be caused by a
number of physical and psychological conditions,
including diabetes, depression, prostate cancer, spinal
cord injury, multiple sclerosis, artherosclerosis, and
heart disease. Injuries to the penis that cause nerve,
tissue, or vascular damage can trigger impotence. It is
also a common side effect of some prescription medications, including antihistamines, antidepressants,
antihypertensives, antipsychotics, beta blockers, diuretics, tranquilizers, appetite suppressants, cimetidine
(Tagamet), and finasteride (Propecia).
A study of African American and Hispanic men
published in 2002 reported that Viagra appears to be
equally safe and equally effective across different
racial and ethnic groups in the United States.
Investigational uses
Although not approved for use in women, clinical
studies have shown that sildenafil citrate may be
3407

Sildenafil citrate

KEY TERMS

Sildenafil citrate

effective in relieving female sexual dysfunction for
some women. In one study, both female and male
study participants who suffered from sexual dysfunction related to their use of such psychotropic medications as benzodiazepines reported an increase in
arousal and overall sexual satisfaction when they
began taking Viagra. Several studies have also indicated the drug may be effective in improving libido
and arousal in women taking selective serotonin
uptake inhibitors (SSRIs).
Another possible use of sildenafil in women is the
treatment of infertility. Women who have had
repeated failures with in vitro fertilization (IVF) due
to poor development of the tissue that lines the uterus
may benefit from treatment with vaginal suppositories
containing sildenafil. One study reported that 70%
of patients had a significant thickening of the uterine
lining, with 29% having a successful implantation of a
new embryo, and 45% achieving ongoing pregnancies.
Another investigational study conducted by
researchers at Johns Hopkins University School of
Medicine in Baltimore, and published in the August
2000 issue of the Journal of Clinical Investigation
found that Viagra may have additional clinical promise for people with diabetes beyond treating ED. In
animal studies, Viagra was effective in relaxing the
pyloric muscle of stomach, improving digestion and
relieving the symptoms of gastroparesis. Up to 75% of
people with diabetes suffer from gastroparesis, which
causes bloating, nausea, loss of appetite, and vomiting.
Further human studies are needed to evaluate Viagra’s
effectiveness in treating this common diabetic
complication.
Because of its capacity to enhance nitric oxide
production, sildenafil has been investigated as a possible treatment for other disorders that are caused by
impaired nitric oxide production. One such disorder is
esophageal motility dysfunction (achalasia), in which
the smooth muscles of the esophagus and the cardiac
sphincter remain constricted, causing difficulty in
swallowing, regurgitation of food, and chest pain
when eating. A study published in 2000 in the journal
Gastroenterology found that sildenafil temporarily
improved the condition in some patients by relaxing
the lower esophageal muscles. An Italian study
reported in 2002 that sildenafil shows genuine promise
as a treatment for spastic esophageal disorders.

Precautions
Viagra is not labeled or approved for use by
women or children, or by men without erectile dysfunction. The medication may also be contraindicated
3408

(not recommended for use) in patients with certain
medical conditions.
Because sexual activity can stress the heart, men
who have heart problems should check with their
physician to see if sexual activity is recommended.
Viagra may trigger temporary hypotension (low
blood pressure) and is known to increase cardiovascular nerve activity, so it is prescribed with caution in
men with a history of heart attack, artherosclerosis,
angina, arrhythmia, and chronic low blood pressure
problems. However, a study published in the March
15, 2001, British Medical Journal found no evidence
that the drug causes a higher incidence of heart attack.
A four-year update on the safety of Viagra published
in September 2002 corroborated the findings of the
British report, and stated that the only absolute contraindication for the use of sildenafil is the concurrent
use of nitrates.
Anyone experiencing cardiovascular symptoms
such as dizziness, chest or arm pain, and nausea
when participating in sexual activity after taking
Viagra should stop the encounter. They should also
not take Viagra again until they have discussed the
episode with their healthcare provider.
It is recommended that men with kidney or liver
impairments, and men over age 65, start at the lowest
possible dosage of Viagra (25 mg). Clinical studies
have shown that the drug builds up in the plasma of
these patients to a concentration that is three to eight
times higher than normal. Caution is also recommended in prescribing the drug to individuals with
retinitis pigmentosa, a rare genetic eye disorder.
Viagra should not be taken more than once per day
by anyone.
Viagra has not been studied for use on patients
with stomach ulcers and bleeding disorders, and its
safety in these individuals is unknown. Men who
have either of these conditions should let their physician know before taking Viagra. It should also be used
with caution in men with misshapen or deformed
penises, such as those with Peyronie’s disease, cavernosal fibrosis, or with angulation of the penis.
Men who take medications containing nitrates
(e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate) should never take Viagra, as the interaction between the two drugs may cause a dramatic
drop in blood pressure, and possibly trigger a heart
attack or stroke. This includes illegal recreational
drugs such as amyl nitrates (also known as poppers).
Viagra may also interact with other prescription
and over-the-counter (OTC) medications, either magnifying or diluting the intended therapeutic effects of
GALE ENCYCLOPEDIA OF MEDICINE

Other medications and therapies for erectile dysfunction, including vacuum or pump devices, drug
injections (Caverject), and urethral suppositories
(MUSE), should never be used in conjunction with
Viagra.

Description
Sildenafil citrate was originally developed in 1991
as a treatment for angina, or chest pain. The drug,
marketed under the name Viagra, received FDA market clearance as a treatment for impotence in March
1998, and since that time it has been prescribed for
over 10 million men worldwide. It was the first oral
medication approved for ED treatment. A newer drug,
tadalafil, has been developed to treat men who do not
respond to sildenafil. Tadalafil has gained preliminary
approval in the European Union (EU), and is in the
final stages of regulatory approval in Canada as of
November 2002.

and insurers may limit coverage to a specific number
of pills each month.

Preparation
Viagra requires time to be absorbed by the body
and become effective. The average recommended time
frame for taking the drug is one hour before initiating
sexual activity, although depending on an individual’s
response to the drug, this time can vary from four
hours to 30 minutes.
Men should always consult with their physician
before beginning treatment with sildenafil citrate. The
medication is not for everyone, and a healthcare professional needs to evaluate medical history and perform a thorough medical examination before
prescribing the drug. In addition, erectile dysfunction
may be a symptom of an undiagnosed condition (i.e.,
diabetes) for which treatment is critical, and may
actually reverse the impotence problem.

Risks
The most commonly reported side effects of
Viagra are headache, flushing of the face, upset stomach, and nasal congestion.

Viagra is a vasodilator, a drug that has the effect
of dilating the blood vessels. It works by improving
blood circulation to the penis, and by enhancing the
effects of nitric oxide, the agent that relaxes the smooth
muscle of the penis and regulates blood vessels during
sexual stimulation, allowing the penis to become
engorged and achieve an erection.

Other less common side effects include, but are
not limited to:

The average recommended dose of Viagra is 50
mg. For men that do not respond adequately to this
amount, the dosage may be increased up to 100 mg or
decreased to 25 mg. The medication is taken approximately one hour before sexual activity is planned, and
may remain effective for up to four hours.
Viagra does not increase sexual desire. Sexual
stimulation and arousal are required for the medication to be effective. Despite its widespread use as a
recreational drug, it is not an aphrodisiac and there is
no clinical evidence that it improves sexual performance in men who are not suffering from ED.
Many insurance plans provide coverage or reimbursement for sildenafil citrate provided it is prescribed to treat erectile dysfunction. A 1999 report
issued by a health insurance consulting group indicated that almost half of the men taking Viagra at
least once weekly receive insurance reimbursement
for the drug. The pills cost approximately $10 each,
GALE ENCYCLOPEDIA OF MEDICINE



vision problems, including sensitivity to light,
blurred vision, and a color tinge to vision



urinary tract infection



diarrhea



dizziness



rash

Side effects may be reduced or eliminated through
adjustments to dosage. Men who experience these
symptoms should consult their physician.
Priapism, a painful and prolonged erection that
lasts for two to six hours, is a rare but potentially
serious side effect of Viagra. Because prolonged erection can permanently damage the tissues of the penis,
anyone who experiences an erection lasting over four
hours should call a healthcare professional
immediately.
Men who are taking Viagra and inadvertently or
intentionally take a medication containing nitrates
may suffer from life-threatening hypotension—a
severe drop in blood pressure.
The cardiovascular risks of sildenafil citrate are
still under investigation. The drug is known to cause
3409

Sildenafil citrate

one or both drugs. Some drugs that have a known
interaction with Viagra include the protease inhibitor
ritonavir and the antibiotic erythromycin. For this
reason, it is critical that men who are prescribed
Viagra let their healthcare providers know all the
medications they are taking.

Sildenafil citrate

KEY TERMS
Angina—Angina pectoris, or chest pain, caused by
an insufficient supply of oxygen and decreased
blood flow to the heart muscle. Angina is frequently
the first sign of coronary artery disease.
Angulation of the penis—Abnormal bend or angle to
the structure of the penis.
Antidepressants—Medications prescribed to relieve
major depression. Classes of antidepressants include
selective serotonin reuptake inhibitors (fluoxetine/
Prozac, sertraline/Zoloft), tricyclics (amitriptyline/
Elavil), MAOIs (phenelzine/Nardil), and heterocyclics
(bupropion/Wellbutrin, trazodone/Desyrel).
Antihistamines—A drug used to treat allergic conditions that counteracts histamines — a substance in
the body that causes itching, vascular changes, and
mucus secretion when released by cells.
Antihypertensives—Medications used to treat high
blood pressure.
Antipsychotics—A class of drugs used to control psychotic symptoms in patients with psychotic disorders
such as schizophrenia and delusional disorder.
Antipsychotics include risperidone (Risperdal), haloperidol (Haldol), and chlorpromazine (Thorazine).
Arrhythmia—Irregular heartbeat caused by erratic
electrical signals or nerve impulses to the cardiac
muscles.
Artherosclerosis—The cause of coronary artery disease, in which the walls of the coronary arteries
thicken due to the accumulation of plaque in the
blood vessels.
Beta blockers—Drugs that lower blood pressure and
reduce stress to the heart by blocking the actions of
beta receptors that control the speed and strength of
heart muscle contractions and blood vessel dilation.

dips in blood pressure and to boost cardiovascular
nerve activity. Some cardiovascular-related deaths
have been reported in men who use Viagra, but it is
unclear whether the fatalities were due to the drug
itself or to the underlying heart disease. Further complicating the picture is the fact that the stress of sexual
activity may have triggered the fatal cardiac event
with or without the use of Viagra. The BMJ study,
and a report published in the April 18, 2001 issue
of the Journal of the American Medical Association
(JAMA) suggest that the drug does not increase
the risk of heart attack. However, JAMA also notes
3410

Cavernosal fibrosis—The formation of abnormal
fibrous tissue in the erectile tissue of the penis.
Diuretics—Any substance that increases urine
output.
Erectile dysfunction—Impotence; the inability of a
man to achieve and/or maintain an erection of sufficient quality for sexual intercourse.
Gastroparesis—Nerve damage of the stomach that
delays or stops stomach emptying, resulting in nausea, vomiting, bloating, discomfort, and weight loss.
Peyronie’s disease—A disease which causes a hardening of the corpora cavernosa, the erectile tissue of
the penis. The penis may become misshapen and/or
curved as a result.
Placebo—An inactive substance with no pharmacological action that is administered to some patients in
clinical trials to determine the relative effectiveness
of another drug administered to a second group of
patients.
Priapism—A painful, abnormally prolonged erection (i.e., four or more hours).
Protease inhibitor—A drug that inhibits the action of
enzymes.
Retinitis pigmentosa—An inherited degenerative
eye disease that impairs night vision and drastically
narrows the field of vision.
Selective serotonin uptake inhibitors (SSRIs)—
Drugs that regulate depression by blocking the
reabsorption of serotonin in the brain consequently
raising serotonin levels. SSRIs include fluoxetine
(Prozac), sertraline (Zoloft), and paroxetine (Paxil).
Serotonin—One of three major neurotransmitters
found in the brain that is linked to emotions.

that further studies are necessary to confirm this
finding.
Although it is a prescription drug, as of early 2001
there was still a thriving illicit market for Viagra via
the Internet. Aside from the health risks recreational
use of the drug poses to individuals with heart conditions and other contraindicated disorders, any adverse
effects caused by Viagra cannot be tracked by regulatory authorities if it has been illegally obtained. In
addition, the drug appears to be toxic in large doses.
In November 2002, a group of French toxicologists
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
When used as directed, Viagra allows men with
erectile dysfunction to achieve and maintain a penile
erection when aroused during sexual activity. Doubleblind, randomized clinical trials of sildenafil citrate
have shown that the drug has an 63–82% efficacy
rate in improving erectile activity among men with
ED, depending on the dose administered (between 25
and 100 mg), compared to a 24% improvement in men
receiving a placebo.
Resources
BOOKS

Medical Economics Company. The Physicians
DeskReference (PDR). 55th ed. Montvale, NJ: Medical
Economics Company, 2001.
Stolar, Mark. Viagra & You. New York:Berkley Books,
1999.
PERIODICALS

Bortolotti, M., N. Pandolfo, M. Giovannini, et al. ‘‘ Effect of
Sildenafil on Hypertensive Lower Oesophageal
Sphincter’’ European Journal of Clinical Investigation 32
(September 2002): 682–685.
Boyce, E. G., and E. M. Umland. ‘‘Sildenafil Citrate: A
Therapeutic Update.’’ Clinical Therapeutics 1 (January
2001): 2–23.
Kuan, J., and G. Brock. ‘‘ Selective Phosphodiesterase Type
5 Inhibition using Tadalafil for the Treatment of
Erectile Dysfunction.’’ Expert Opinion on
Investigational Drugs 11 (November 11, 2002): 1605–
1613.
Mitka, Mike. ‘‘Studies of Viagra Offer Some Reassurance to
Men With Concerns About Cardiac Effects.’’ The
Journal of the American Medical Association 285, no.15
(April 18, 2001): 1950.
Padma-nathan, H., I. Eardley, R. A. Kloner, et al. ‘‘ A 4-year
Update on the Safety of Sildenafil Citrate (Viagra).’’
Urology 60, no.2, Supplement 2 (September 2002):
67–90.
Shakir, S. A., et al. ‘‘Cardiovascular Events in Users of
Sildenafil: Results from First Phase of Prescription
Event Monitoring in England.’’ British Medical Journal
322, no.7287 (March 17, 2001): 651–2.
Sher, G., and J. D. Fisch. ‘‘ Effect of Vaginal Sildenafil on
the Outcome of in vitro Fertilization (IVF) After
Multiple IVF Failures Attributed to Poor Endometrial
Development.’’ Fertility and Sterility 78 (November
2002): 1256–1257.
Tracqui, A., A. Miras, A. Tabib, et al. ‘‘ Fatal Overdosage
with Sildenafil Citrate (Viagra): First Report and
Review of the Literature.’’ Human and Experimental
Toxicology 21 (November 2002): 623–629.
GALE ENCYCLOPEDIA OF MEDICINE

‘‘Viagra Increases Nerve Activity Associated with
Cardiovascular Function.’’ Drug Week January 26,
2001: 11.
Young, J. M., C. Bennett, P. Gilhooly, et al. ‘‘ Efficacy and
Safety of Sildenafil Citrate (Viagra) in Black and
Hispanic American Men.’’ Urology 60, no. 2,
Supplement 2 (September 2002): 39–48.
ORGANIZATIONS

American Heart Association. American Heart Association.
7320 Greenville Ave. Dallas, TX 75231. (214) 373-630
or (800) 242-8721. inquire@heart.org.
<http://www.americanheart.org>.
U.S. Food and Drug Administration (FDA), Center for
Drug Evaluation and Research. Viagra Information.
<http://www.fda.gov/cder/consumerinfo/
viagra/default.htm>.
OTHER

Pfizer, Inc. Viagra Information Site.
<http://www.viagra.com/>.

Paula Anne Ford-Martin
Rebecca J. Frey, PhD

Silent thyroiditis see Thyroiditis

Silicosis
Definition
Silicosis is a progressive disease that belongs to a
group of lung disorders called pneumoconioses.
Silicosis is marked by the formation of lumps
(nodules) and fibrous scar tissue in the lungs. It is the
oldest known occupational lung disease, and is caused
by exposure to inhaled particles of silica, mostly from
quartz in rocks, sand, and similar substances.

Description
It is estimated that there are TWO million workers
in the United States employed in occupations at risk
for the development of silicosis. These include miners,
foundry workers, stonecutters, potters and ceramics
workers, sandblasters, tunnel workers, and rock drillers. Silicosis is mostly found in adults over 40. It has
four forms:


Chronic. Chronic silicosis may take 15 or more years
of exposure to develop. There is only mild impairment of lung functioning. Chronic silicosis may progress to more advanced forms.



Complicated. Patients with complicated silicosis
have noticeable shortness of breath, weight loss, and
3411

Silicosis

reported the case of a 56-year-old male who took a
fatal overdose of Viagra.

Silicosis

extensive formation of fibrous tissue (fibrosis) in the
lungs. These patients are at risk for developing tuberculosis (TB).


Accelerated. This form of silicosis appears after 5-10
years of intense exposure. The symptoms are similar
to those of complicated silicosis. Patients in this
group often develop rheumatoid arthritis and other
autoimmune disorders.



Acute. Acute silicosis develops within six months to
two years of intense exposure to silica. The patient
loses a great deal of weight and is constantly short of
breath. These patients are at severe risk of TB.

KEY TERMS
Fibrosis—The development of excess fibrous connective tissue in an organ. Fibrosis of the lungs is a
symptom of silicosis.
Pneumoconiosis (plural, pneumoconioses)—Any
chronic lung disease caused by inhaling particles
of silica or similar substances that lead to loss of
lung function.
Silica—A substance (silicon dioxide) occurring in
quartz sand, flint, and agate. It is used in making
glass, scouring and grinding powders, pottery, etc.

Causes and symptoms
The precise mechanism that triggers the development of silicosis is still unclear. What is known is that
particles of silica dust get trapped in the tiny sacs
(alveoli) in the lungs where air exchange takes place.
White blood cells called macrophages in the alveoli
ingest the silica and die. The resulting inflammation
attracts other macrophages to the region. The nodule
forms when the immune system forms fibrous tissue to
seal off the reactive area. The disease process may stop
at this point, or speed up and destroy large areas of the
lung. The fibrosis may continue even after the worker
is no longer exposed to silica.
Early symptoms of silicosis include shortness of
breath after exercising and a harsh, dry cough.
Patients may have more trouble breathing and cough
up blood as the disease progresses. Congestive heart
failure can give their nails a bluish tint. Patients with
advanced silicosis may have trouble sleeping and
experience chest pain, hoarseness, and loss of appetite.
Silicosis patients are at high risk for TB, and should be
checked for the disease during the doctor’s
examination.

Diagnosis
Diagnosis of silicosis is based on:


A detailed occupational history.



Chest x rays will usually show small round opaque
areas in chronic silicosis; the round areas are larger in
complicated and accelerated silicosis.



bronchoscopy



lung function tests

It should be noted that the severity of the patient’s
symptoms does not always correlate with x-ray findings or lung function test results.
3412

Treatment
Symptom management
There is no cure for silicosis. Therapy is intended
to relieve symptoms, treat complications, and prevent
respiratory infections. It includes careful monitoring
for signs of TB. Respiratory symptoms may be treated
with bronchodilators, increased fluid intake, steam
inhalation, and physical therapy. Patients with severe
breathing difficulties may be given oxygen therapy or
placed on a mechanical ventilator. Acute silicosis may
progress to complete respiratory failure. Heart-lung
transplants are the only hope for some patients.
Patients with silicosis should call their doctor for
any of the following symptoms:


tiredness or mental confusion



continued weight loss



coughing up blood



fever, chest pain, breathlessness, or new unexplained
symptoms
Lifestyle changes

Patients with silicosis should be advised to quit
smoking, prevent infections by avoiding crowds and
persons with colds or similar infections, and receive
vaccinations against influenza and pneumonia. They
should be encouraged to increase their exercise capacity by keeping up regular activity, and to learn to pace
themselves with their daily routine.

Prognosis
Silicosis is currently incurable. The prognosis for
patients with chronic silicosis is generally good. Acute
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
Silicosis is a preventable disease. Preventive occupational safety measures include:


controls to minimize workplace exposure to silica
dust



substitution of substances–especially in sandblasting–
that are less hazardous than silica



clear identification of dangerous areas in the
workplace



Informing workers about the dangers of overexposure to silica dust, training them in safety techniques,
and giving them appropriate protective clothing and
equipment.

Coworkers of anyone diagnosed with silicosis
should be examined for symptoms of the disease. The
state health department and the Occupational Safety
and Health Administration (OSHA) or the Mine
Safety and Health Administration (MSHA) must be
notified whenever a diagnosis of silicosis is confirmed.

Purpose
Sinus endoscopy is used to help diagnose structural defects, infection or damage to the sinuses, or
structures in the nose and throat. It may be used to
view polyps and growths in the sinuses and to investigate causes of recurrent inflammation of the sinuses
(sinusitis). During surgical procedures, an endoscope
may be used to view the area to correct sinus-drainage
problems or to remove polyps from the nose and
throat.

Precautions
Insertion of the endoscope may cause a gag reflex
and some discomfort, however, no special precautions
are required to prepare for nasal endoscopy.

Description
This procedure can be done in a physician’s office.
The endoscope is inserted into a nostril and is threaded
through the sinus passages to the throat. To make
viewing of these areas easier, and to record the areas
being examined, a camera, monitor, or other such
viewing device is connected to the endoscope

Resources

Preparation

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Maureen Haggerty

For the procedure, the patient is usually awake
and seated upright in a chair. A local anesthetic spray
or liquid may be applied to the throat to make insertion of the endoscope less uncomfortable.

Aftercare

Silo-filler’s disease see Lung diseases due to
gas or chemical exposure
Simethicone see Antigas agents
Singer’s nodules see Vocal cord nodules and
polyps

Sinus endoscopy
Definition
An endoscope is a narrow flexible tube which
contains an optical device like a telescope or magnifying lens with a bright light. In sinus endoscopy, the
endoscope is inserted into the nose, and the interior of
the nasal passages, sinuses, and throat is examined.
GALE ENCYCLOPEDIA OF MEDICINE

After the endoscope is removed, the patient can
return to most normal activities. If an anesthetic was
used, the patient may have to wait until the numbness
wears off to be able to eat or drink.

Risks
The insertion and removal of the endoscope may
stimulate a gag reflex, and can cause some discomfort.
The procedure may also irritate the tissues of the nose
and throat, causing a nosebleed or coughing.

Normal results
Under normal conditions, no polyps, or growths
are found in the sinuses. There should also be no
evidence of infection, swelling, injury, or any structural defect that would prevent normal draining of the
sinuses.
3413

Sinus endoscopy

silicosis, however, may progress rapidly to respiratory
failure and death.

Sinusitis

Abnormal results
Polyps, growths, infections, or structural defects
of the nasal passages are considered abnormal.

the normal flow of mucus. Trapped mucus can then fill
the sinuses, causing an uncomfortable sensation of
pressure and providing an excellent environment for
the growth of infection-causing bacteria.

Resources

Causes and symptoms

ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
Ear Foundation. 1817 Patterson St., Nashville, TN 37203.
(800) 545-4327. <http://www.earfoundation.org>.
OTHER

‘‘Endoscopic Plastic Surgery.’’ Southern California Plastic
Surgery Group’ Page. <http://www.facedoctor.com>.

Altha Roberts Edgren

Sinus x ray see Skull x rays

Sinusitis
Definition
Sinusitis refers to an inflammation of the sinuses,
airspaces within the bones of the face. Sinusitis is most
often due to an infection within these spaces.

Description
The sinuses are paired air pockets located within
the bones of the face. They are:


the frontal sinuses; located above the eyes, in the
center region of each eyebrow



the maxillary sinuses; located within the cheekbones,
just to either side of the nose



the ethmoid sinuses; located between the eyes, just
behind the bridge of the nose.



the sphenoid sinuses; Located just behind the
ethmoid sinuses, and behind the eyes.

The sinuses are connected with the nose. They are
lined with the same kind of skin found elsewhere
within the respiratory tract. This skin has tiny little
hairs projecting from it, called cilia. The cilia beat
constantly, to help move the mucus produced in the
sinuses into the respiratory tract. The beating cilia
sweeping the mucus along the respiratory tract helps
to clear the respiratory tract of any debris, or any
organisms which may be present. When the lining of
the sinuses is at all swollen, the swelling interferes with
3414

Sinusitis is almost always due to an infection,
although swelling from allergies can mimic the symptoms of pressure, pain, and congestion; and allergies
can set the stage for a bacterial infection. Bacteria
are the most common cause of sinus infection.
Streptococcus pneumoniae causes about 33% of all
cases, while Haemophilus influenzae causes about
25% of all cases. Sinusitis in children may be caused
by Moraxella catarrhalis (20%). In people with weakened immune systems (including patients with diabetes; acquired immunodeficiency syndrome or AIDS;
and patients who are taking medications which lower
their immune resistance, such as cancer and transplant
patients), sinusitis may be caused by fungi such as
Aspergillus, Candida, or Mucorales.
Acute sinusitis usually follows some type of upper
respiratory tract infection or cold. Instead of ending,
the cold seems to linger on, with constant or even
worsening congestion. Drainage from the nose often
changes from a clear color to a thicker, yellowishgreen. There may be fever. Headache and pain over
the affected sinuses may occur, as well as a feeling of
pressure which may worsen when the patient bends
over. There may be pain in the jaw or teeth. Some
children, in particular, get upset stomachs from the
infected drainage going down the back of their
throats, and being swallowed into their stomachs.
Some patients develop a cough.
Chronic sinusitis occurs when the problem has
existed for at least three months. There is rarely a
fever with chronic sinusitis. Sinus pain and pressure
is frequent, as is nasal congestion. Because of the
nature of the swelling in the sinuses, they may not be
able to drain out the nose. Drainage, therefore, drips
constantly down the back of the throat, resulting in a
continuously sore throat and bad breath.

Diagnosis
Diagnosis is sometimes tricky, because the symptoms so often resemble those of an uncomplicated
cold. However, sinusitis should be strongly suspected
when a cold lingers beyond about a week’s time.
Medical practitioners have differing levels of trust
of certain basic examinations commonly conducted in
the office. For example, tapping over the sinuses may
GALE ENCYCLOPEDIA OF MEDICINE

Sinusitis

Frontal sinus
Sphenoidal sinus

Ethmoidal sinus

Maxillary sinus

Sinusitis is the inflammation of the sinuses caused by a bacterial infection. Sometimes diagnosis may be problematic because
the symptoms often mimic those of the common cold. Sinusitis is usually treated with antibiotics. (Illustration by Electronic
Illustrators Group.)

cause pain in patients with sinusitis, but it may not. A
procedure called ‘‘sinus transillumination’’ may, or
may not, also be helpful. Using a flashlight pressed up
against the skin of the cheek, the practitioner will look
in the patient’s open mouth. When the sinuses are full of
air (under normal conditions), the light will project
through the sinus, and will be visible on the roof of
the mouth as a lit-up, reddened area. When the sinuses
are full of mucus, the light will be stopped. While this
simple test can be helpful, it is certainly not a perfect
way to diagnose or rule out the diagnosis of sinusitis.
X-ray pictures and CT scans of the sinuses are
helpful for both acute and chronic sinusitis. People
with chronic sinusitis should also be checked for allergies; and they may need a procedure with a scope to see
if any kind of anatomic obstruction is causing their
illness. For example, the septum (the cartilage which
separates the two nasal cavities from each other) may
be slightly displaced, called a deviated septum. This can
result in chronic obstruction, setting the person up for
the development of an infection.

for even longer periods of time. Decongestants, or the
short-term use of decongestant nose sprays, can be
useful. Acetaminophen and ibuprofen can decrease the
pain and headache associated with sinusitis. Also, running a humidifier can prevent mucus within the nasal
passages from drying out uncomfortably, and can help
soothe any accompanying sore throat or cough.
Chronic sinusitis is often treated initially with
antibiotics. Steroid nasal sprays may be used to
decrease swelling in the nasal passages. If an anatomic
reason is found for chronic sinusitis, it may need to be
corrected with surgery. If a surgical procedure is necessary, samples are usually taken at the same time to
allow identification of any organisms present which
may be causing infection.
Fungal sinusitis will require surgery to clean out
the sinuses. Then, a relatively long course of a very
strong antifungal medication called amphotericin B is
given through a needle in the vein (intravenously).

Alternative treatment
Treatment
Antibiotic medications are used to treat acute sinusitis. Suitable antibiotics include sulfa drugs, amoxicillin, and a variety of cephalosporins. These medications
are usually given for about two weeks, but may be given
GALE ENCYCLOPEDIA OF MEDICINE

Chronic sinusitis is often associated with food
allergies. An elimination/challenge diet is recommended to identify and eliminate allergenic foods.
Irrigating the sinuses with a salt water solution is
often recommended for sinusitis and allergies, in
3415

Situs inversus

KEY TERMS
Cilia—Tiny, hair-like projections from a cell.
Within the respiratory tract, the cilia act to move
mucus along, in an effort to continually flush out
and clean the respiratory tract.
Sinus—An air-filled cavity.

inflammation within the nasal passageways, thus
allowing the normal flow of mucus.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.

Rosalyn Carson-DeWitt, MD
order to clear the nasal passages of mucus. Another
solution for nasal lavage (washing) utilizes powdered
goldenseal (Hydrastis canadensis). Other herbal treatments, taken internally, include a mixture made of
eyebright (Euphrasia officinalis), goldenseal, yarrow
(Achillea millefolium), horseradish, and ephedra
(Ephedra sinica), or, when infection is present, a mixture made of echinacea (Echinacea spp.), wild indigo,
and poke root (Phytolacca decandra-Americana).
Homeopathic practitioners find a number of
remedies useful for treating sinusitis. Among those
they recommend are: Arsenicum album, Kalium bichromium, Nux vomica, Mercurius iodatus, and Silica.
Acupuncture has been used to treat sinusitis, as
have a variety of dietary supplements, including vitamins A, C, and E, and the mineral zinc. Contrast
hydrotherapy (hot and cold compresses, alternating 3
minutes hot, 30 seconds cold, repeated 3 times always
ending with cold) applied directly over the sinuses can
relieve pressure and enhance healing. A direct inhalation of essential oils (2 drops of oil to 2 cups of water)
using thyme, rosemary, and lavender can help open
the sinuses and kill bacteria that cause infection.

Prognosis
Prognosis for sinus infections is usually excellent,
although some individuals may find that they are particularly prone to contracting such infections after a
cold. Fungal sinusitis, however, has a relatively high
death rate.

Prevention
Prevention involves the usual standards of good
hygiene to cut down on the number of colds an individual catches. Avoiding exposure to cigarette smoke,
identifying and treating allergies, and avoiding deep
dives in swimming pools may help prevent sinus infections. During the winter, it is a good idea to use a
humidifier. Dry nasal passages may crack, allowing
bacteria to enter. When allergies are diagnosed, a
number of nasal sprays are available to try to prevent
3416

Situs inversus
Definition
Situs inversus is a condition in which the organs of
the chest and abdomen are arranged in a perfect mirror image reversal of the normal positioning.

Description
Normal human development results in an asymmetrical arrangement of the organs within the chest
and abdomen. Typically, the heart lies on the left side
of the body (levocardia), the liver and spleen lie on the
right, and the lung on the left has two lobes while the
lung on the right has three lobes. This normal arrangement is known as situs solitus.
However, in about 1 in 8,500 people, the organs of
the chest and abdomen are arranged in the exact
opposite position: the heart is on the right (dextrocardia), as is the two-lobed lung, and the liver, spleen, and
three-lobed lung are on the left. Yet because this
arrangement, called situs inversus, is a perfect mirror
image, the relationship between the organs is not
changed, so functional problems rarely occur.

Causes and symptoms
Early in the normal development of an embryo,
the tube-like structure that becomes the heart forms a
loop toward the left, identifying the left/right axis
along which the other organs should be positioned.
Although the mechanism that causes the heart loop to
go left is not fully understood, at least one gene has
been identified to have a role in this process. However,
it is thought that many factors may be involved in
causing situs inversus. Rarely, situs inversus can run
in families, but most often it is an isolated and accidental event occurring in an individual for the first
time in the family.
GALE ENCYCLOPEDIA OF MEDICINE

It is estimated that about 25% of people with situs
inversus have an underlying condition called primary
ciliary dyskinesia (PCD). PCD, also known as
Kartagener’s syndrome, is characterized as situs inversus, chronic sinus infections, increased mucous secretions from the lungs, and increased susceptibility to
respiratory infections. PCD is caused by a defect in the
cilia that impairs their normal movements.

Diagnosis
Situs inversus should detected by a thorough physical examination. It is often picked up when a physician, using a stethoscope, hears otherwise normal
heart sounds on the right side of the body instead of
the left. To confirm the a suspected diagnosis of situs
inversus, imaging studies such as MRI, CT, or ultrasound may be ordered, and a referral may be made to a
cardiologist or internist for completeness. Imaging
studies will also rule out the possibility of random
arrangement of the organs, or heterotaxy, which has
a much higher risk for serious medical complications.

Treatment
There is no treatment for situs inversus. In the
unlikely case that a heart defect is present, it should
be treated accordingly by a cardiologist.
Individuals who have situs inversus should be sure
to inform all physicians involved in their medical care.
In addition to preventing unnecessary confusion, this
will reduce the risk of missing a crucial diagnosis that
presents with location-specific symptoms (such as
appendicitis).

KEY TERMS
Cilia—Tiny hairlike projections on certain cells
within the body; cilia produce lashing or whipping
movements to direct or cause motion of substances
or fluids within the body.
Gene—A single unit of genetic information, providing the body with instruction for a specific biological task.
MRI—An imaging study that uses magnetic forces
to produce an image of the body’s internal
structures.
CT—A special technique that uses a computer to
create a cross-sectional image of the body from a
series of x rays.
Ultrasound—An imaging study that uses high-frequency sound waves to form a visual image of the
body’s internal structures.

Resources
PERIODICALS

Ainsworth, Claire. ‘‘Left Right and Wrong.’’ New Scientist
66, no. 2243 (June 17, 2000): 40-45.
Janchar, T., Milzman, D., and Clement, M. ‘‘Situs Inversus:
Emergency Evaluations of Atypical Presentations.’’
American Journal of Emergency Medicine 18, no. 3
(May 2000): 349-50.
Travis, John. ‘‘Twirl Those Organs into Place.’’ Science
News 156, no. 8 (21 August 1999): 124-125.
ORGANIZATIONS

American Heart Association. National Center. 7272
Greenville Avenue, Dallas, TX 75231-4596. (214)
373-6300. (800) 242-8721. inquire@heart.org.
NIH/National Heart, Lung and Blood Institute Information
Center. P.O. Box 30105. Bethesda, MD 20824-0105.
(301) 592-8573.

Stefanie B. N. Dugan, M.S.

Alternative treatment
Not applicable.

Prognosis
The prognosis for an individual with situs inversus
is good, and in the absence of a heart defect or other
underlying diagnosis, life expectancy is normal.

Prevention
There is no known method of preventing situs
inversus.
GALE ENCYCLOPEDIA OF MEDICINE

Sitz bath
Definition
A sitz bath (also called a hip bath) is a type of bath
in which only the hips and buttocks are soaked in
water or saline solution. Its name comes from the
German verb ‘‘sitzen,’’ meaning ‘‘to sit.’’
3417

Sitz bath

Most people with situs inversus have no medical
symptoms or complications resulting from the condition. Although only 3-5% of people with situs inversus
have any type of functional heart defect, this is higher
than the rate of heart defects in the general population,
which is less than 1%.

Sitz bath
Equipment used for sitz baths. A sitz bath, in which only the hips and buttocks are soaked in water or saline solution, is used for
patients who have had surgery in the rectal area or to ease discomfort from bladder, prostate, or vaginal infections. (Illustration by
Electronic Illustrators Group.)

Purpose
A sitz bath is used for patients who have had
surgery in the area of the rectum, or to ease the pain
of hemorrhoids, uterine cramps, prostate infections,
painful ovaries, and/or testicles. It is also used to
ease discomfort from infections of the bladder, prostate, or vagina. Inflammatory bowel diseases are also
treated with sitz baths.

Precautions
Some patients may become dizzy when standing
up after sitting in hot water; it is best to have someone
else present when doing a contrast sitz bath.

Description
The sitz bath is a European tradition in which
only the pelvis and abdominal area are placed in
water, with the upper body, arms, legs, and feet out
of the water. The water can be warm or cool and one
or two tubs may be used.
3418

Warm sitz baths are one of the easiest and most
effective ways to ease the pain of hemorrhoids. A
warm bath is also effective in lessening the discomfort
associated with genital herpes, uterine cramps, and
other painful conditions in the pelvic area.
For prostate pain, patients should take two hot
sitz baths a day, for about 15 minutes each.
To ease discomfort from a vaginal yeast infection,
women should take a warm saline sitz bath. To prepare, fill the tub to hip height with warm water and
add 1/2 c of salt (enough to make the water taste salty)
and 1/2 vinegar. Sit in the bath for 20 minutes (or until
the water gets cool). The vinegar will help bring the
vaginal pH back to 4.5 (pH is a measurement of how
acid or alkaline a fluid is).
A brief, cool sitz bath helps ease inflammation,
constipation, and vaginal discharge. It can be used to
tone the muscles in cases of bladder or bowel
incontinence.
Other conditions respond to a ‘‘contrast bath’’ of
both hot and cold. For this a patient should have a tub
GALE ENCYCLOPEDIA OF MEDICINE

pH—A standard laboratory test that measures how
acidic or alkaline a solution is.
Saline solution—Another word for salt water.

of hot water (about 1108F/438C) and one tub of ice
water. The patient should sit in the hot water for three
to four minutes and in the cold for 30–60 seconds. This
is repeated three to five times, always ending with the
cold water.
If two tubs are not handy, the patient may sit in a
hot bath (up to the navel). Then the patient stands up
in the water and pulls a cold towel between the legs and
over the pelvis in front and back. The cold towel is held
in place for up to 60 seconds. Then the patient should
sit back into the hot bath, and repeat the process 3–5
times, ending with the cold towel.

Preparation
The bath should be filled with 3–4 in (8–10cm) of
water. For most conditions, nothing else should be
added (no bubble bath or oil).

Aftercare
The area should be carefully patted dry and, if
necessary, clean dressings should be applied.

Risks
Sitz baths pose almost no risk. On rare occasions,
patients can feel dizzy or experience rapid heart beat
because of blood vessel dilation.

Normal results
Swelling goes down; discomfort is eased; healing is
promoted.
Carol A. Turkington

Sjögren’s syndrome
Definition
Sjögren’s syndrome (SS) is a disorder in which the
mouth and eyes become extremely dry. Sjögren’s
GALE ENCYCLOPEDIA OF MEDICINE

syndrome is often associated with other autoimmune
disorders. It is named for Henrik Sjögren, a Swedish
ophthalmologist.

Description
Like other autoimmune disorders, Sjögren’s syndrome occurs when the body’s immune system mistakenly begins treating parts of the body as foreign
invaders. While the immune cells should attack and
kill invaders like bacteria, viruses, and fungi, these
cells should not attack the body itself. In autoimmune
disorders, however, cells called antibodies see tissues of
the body as foreign, and help to start a chain of events
that results in damage and destruction of those tissues.
There are three types of Sjögren’s syndrome.
Primary Sjögren’s syndrome occurs by itself, with no
other associated disorders. Secondary Sjögren’s syndrome occurs along with other autoimmune disorders,
like systemic lupus erythematosus, rheumatoid arthritis, scleroderma, vasculitis, or polymyositis. When the
disorder is limited to involvement of the eyes, with no
other organ or tissue involvement evident, it is called
sicca complex.
Women are about nine times more likely to suffer
from Sjögren’s syndrome than are men. SS affects all
age groups, although most patients are diagnosed when
they are between 40 and 55 years old. Sjögren’s syndrome is commonly associated with other autoimmune
disorders. In fact, 30% of patients with certain autoimmune disorders will also have Sjögren’s syndrome.
SS is found in all races and ethnic groups. It is
thought to affect between 0.1% and 3% of the population in the United States; this range reflects the lack
of a uniform set of diagnostic criteria. According to
the American College of Rheumatology, between 1
million and 4 million Americans have Sjögren’s
syndrome.

Causes and symptoms
The cause of Sjögren’s syndrome has not been
clearly defined, but several causes are suspected. The
syndrome sometimes runs in families. Other potential
causes include hormonal factors (since there are more
women than men with the disease) and viral factors.
The viral theory suggests that the immune system is
activated in response to a viral invader, but then fails
to turn itself off. Some other immune malfunction
then causes the overly active immune system to begin
attacking the body’s own tissues. In 2004 a group of
Greek researchers presented evidence that a coxsackievirus may be the disease organism that triggers SS.
3419

Sjögren’s syndrome

KEY TERMS

Sjögren’s syndrome

The main problem in Sjögren’s syndrome is dryness. The salivary glands are often attacked and
slowly destroyed, leaving the mouth extremely dry
and sticky. Swallowing and talking become difficult.
Normally, the saliva washes the teeth clean. Saliva
cannot perform this function in Sjögren’s syndrome,
so the teeth develop many cavities and decay quickly.
The parotid glands produce the majority of the
mouth’s saliva. They are located lying over the jaw
bones behind the area of the cheeks and in front of the
ears, and may become significantly enlarged in
Sjögren’s syndrome.
The eyes also become extremely dry as the tear
glands (called glands of lacrimation) are slowly
destroyed. Eye symptoms include itching, burning,
redness, increased sensitivity to light, and thick secretions gathering at the eye corners closest to the nose.
The cornea may have small irritated pits in its surface
(ulcerations).
Destruction of glands in other areas of the body
may cause a variety of symptoms. In the nose, dryness
may result in nosebleeds. In the rest of the respiratory
tract, the rates of ear infection, hoarseness, bronchitis,
and pneumonia may increase. Vaginal dryness can be
quite uncomfortable. Rarely, the pancreas may slow
production of enzymes important for digestion. The
kidney may malfunction. About 33% of all patients
with Sjögren’s syndrome have other symptoms unrelated to gland destruction. These symptoms include
fatigue, decreased energy, fevers, muscle aches and
pains, and joint pain.
Many patients with SS also develop a variety of
skin problems that include dry patches, vasculitis, and
cutaneous B-cell lymphoma. These and other dermatologic disorders are more common in SS than was
previously thought.
Patients who also have other autoimmune diseases will suffer from the symptoms specific to those
conditions.
In addition to physical symptoms, patients with
SS appear to be at increased risk for depression and
other mood disorders.

Diagnosis
Diagnosis of Sjögren’s syndrome is based on the
patient having at least three consecutive months
of bothersome eye and/or mouth dryness. A variety
of tests can then be done to determine the quantity of
tears produced, the quantity of saliva produced, and
the presence or absence of antibodies that could be
involved in the destruction of glands.
3420

KEY TERMS
Autoimmune disorder—A disorder in which the
body’s immune cells mistake the body’s own tissues as foreign invaders; the immune cells then
work to destroy tissues in the body.
Cornea—A transparent structure of the eye over the
iris and pupil; light must pass through the cornea to
make vision possible.
Coxsackievirus—Any of a group of enteroviruses
that produce a disease in humans characterized
by fever and rash. Coxsackieviruses are named for
the town in upstate New York where they were first
identified.
Immune system—The complex network of organs
and blood cells that protect the body from foreign
invaders, like bacteria, viruses, and fungi.

Treatment
There is no cure for Sjögren’s syndrome. Instead,
treatment usually attempts to reduce the discomfort
and complications associated with dryness of the eyes
and mouth (and other areas). Artificial tears are available, and may need to be used up to every 30 minutes.
By using these types of products, the patient is more
comfortable and avoids the complications associated
with eyes that are overly dry. Dry mouth is treated by
sipping fluids slowly but constantly throughout the
day. Sugarless chewing gum can also be helpful. An
artificial saliva is available for use as a mouthwash.
Patients may also be given such drugs as pilocarpine
(Salagen) or cevimeline (Evoxac) to increase saliva
and tear secretions. Careful dental hygiene is important in order to avoid tooth decay, and it is wise for
patients to decrease sugar intake. Vaginal dryness can
be treated with certain gel preparations. Steroid medications may be required when other symptoms of
autoimmune disorders complicate Sjögren’s syndrome. However, these medications should be avoided
when possible because they may make the cornea thin
and even more susceptible to injury.

Prognosis
The prognosis for patients with primary Sjögren’s
syndrome is particularly good; these patients have a
normal life expectancy. Although the condition is
quite annoying, serious complications rarely occur.
The prognosis for patients with secondary Sjögren’s
syndrome varies since it depends on the prognosis for
the accompanying autoimmune disorder.
GALE ENCYCLOPEDIA OF MEDICINE

Since the cause of Sjögren’s syndrome is unknown
as of 2004, there are no known ways to prevent this
syndrome.

Skeletal traction see Traction;
Immobilization

Skin biopsy

Prevention

Skin abrasion see Skin resurfacing
Skin allergy test see Allergy tests

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Diffuse Connective Tissue Disease.’’ Section 5,
Chapter 50 In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Moutsopoulos, Haralampos M. ‘‘Sjögren’s Syndrome.’’ In
Harrison’s Principles of Internal Medicine, edited by
Anthony S. Fauci, et al. New York: McGraw-Hill,
1997.
PERIODICALS

Bell, Mary, et al. ‘‘Sjögren’s Syndrome: A Critical Review of
Clinical Management.’’ The Journal of Rheumatology
26, no. 9 (2001): 2051–2059.
Francis, Mark L., MD. ‘‘Sjogren Syndrome.’’ eMedicine
July 1, 2004. <http://emedicine.com/med/
topic2136.htm>.
Ono, M., E. Takamura, K. Shinozaki, et al. ‘‘Therapeutic
Effect of Cevimeline on Dry Eye in Patients with
Sjögren’s Syndrome: A Randomized, Double-Blind
Clinical Study.’’ American Journal of Ophthalmology
138 (July 2004): 6–17.
Roguedas, A. M., L. Misery, B. Sassolas, et al. ‘‘Cutaneous
Manifestations of Primary Sjögren’s Syndrome Are
Underestimated.’’ Clinical and Experimental
Rheumatology 22 (September-October 2004): 632–636.
Stevenson, H. A., M. E. Jones, J. L. Rostron, et al. ‘‘UK
Patients with Primary Sjögren’s Syndrome Are at
Increased Risk from Clinical Depression.’’
Gerodontology 21 (September 2004): 141–145.
Triantafyllopoulou, A., N. Tapinos, and H. M.
Moutsopoulos. ‘‘Evidence for Coxsackievirus Infection
in Primary Sjögren’s Syndrome.’’ Arthritis and
Rheumatism 50 (September 2004): 2897–2902.
ORGANIZATIONS

American College of Rheumatology. 1800 Century Place,
Suite 250, Atlanta, GA 30345-4300. (404) 633-3777.
Fax: (404) 633-1870. <http://
www.rheumatology.org>.
Sjögren’s Syndrome Foundation, Inc. 8120 Woodmont
Avenue, Bethesda, MD 20814. (800) 475-6473. Fax:
(301) 718-0322. <http://www.sjogrens.org>.

Skin biopsy
Definition
A skin biopsy is a procedure in which a small piece
of living skin is removed from the body for examination, usually under a microscope, to establish a precise
diagnosis. Skin biopsies are usually brief, straightforward procedures performed by a skin specialist
(dermatologist) or family physician.

Purpose
The word biopsy is taken from Greek words that
mean ‘‘to view life.’’ The term describes what a specialist in identifying diseases (pathologist) does with tissue obtained from a skin biopsy. The pathologist
visually examines the tissue under a microscope.
A skin biopsy is used to make a diagnosis of many
skin disorders. Information from the biopsy also helps
the doctor choose the best treatment for the patient.
Doctors perform skin biopsies to:


make a diagnosis



confirm a diagnosis made from the patient’s medical
history and a physical examination



check whether a treatment prescribed for a previously diagnosed condition is working



check the edges of tissue removed with a tumor to
make certain it contains all the diseased tissue

Skin biopsies also can serve a therapeutic purpose.
Many skin abnormalities (lesions) can be removed
completely during the biopsy procedure.

Precautions

American College of Rheumatology Fact Sheet. ‘‘Sjögren’s
Syndrome.’’ <http://www.rheumatology.org/public/
factsheets/sjogrens_new.asp?aud=pat>.

A patient taking aspirin or another blood thinner
(anticoagulant) may be asked to stop taking them a
week or more before the skin biopsy. This adjustment
in medication will prevent excessive bleeding during
the procedure and allow for normal blood clotting.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

Some patients are allergic to lidocaine, the numbing
agent most frequently used during a skin biopsy. The
doctor can usually substitute another anesthetic agent.

OTHER

GALE ENCYCLOPEDIA OF MEDICINE

3421

Skin biopsy

Description
The first part of the skin biopsy test is obtaining a
sample of tissue that best represents the lesion being
evaluated. Many biopsy techniques are available. The
choice of technique and precise location from which to
take the biopsy material are determined by factors
such as the type and shape of the lesion. Biopsies can
be classified as excisional or incisional. In excisional
biopsy, the lesion is completely removed; in incisional
biopsy, a portion of the lesion is removed.
The most common biopsy techniques are:


Shave biopsy. A scalpel or razor blade is used to
shave off a thin layer of the lesion parallel to the skin.



Punch biopsy. A small cylindrical punch is screwed
into the lesion through the full thickness of the skin
and a plug of tissue is removed. A stitch or two may
be needed to close the wound.



Scalpel biopsy. A scalpel is used to make a standard
surgical incision or excision to remove tissue. This
technique is most often used for large or deep lesions.
The wound is closed with stitches.



Scissors biopsy. Scissors are used to snip off surface
(superficial) skin growths and lesions that grow from
a stem or column of tissue. Such growths are sometimes seen on the eyelids or neck.

After the biopsy tissue is removed, bleeding may
be controlled by applying pressure or by burning with
electricity or chemicals. Antibiotics often are applied
to the wound to prevent infection. Stitches may be
placed in the wound, or the wound may be bandaged
and allowed to heal on its own.
The second part of the skin biopsy test is handling
and examining the tissue sample. Drying and structural damage to the tissue sample must be prevented,
so it should be placed immediately in an appropriate
preservative, such as formaldehyde.
The pathologist can use a variety of laboratory
techniques to process the biopsy tissue. Tissue stains
and several different kinds of microscopes are used.
Because there are many skin disorders (broadly called
dermatosis and dermatitis), the pathologist has extensive training in their accurate identification. Cases of
melanoma, the most malignant kind of skin cancer,
have almost tripled in the past 30 years. Because melanoma grows very rapidly in the skin, quick and accurate diagnosis is important.

KEY TERMS
Benign—Noncancerous.
Dermatitis—A skin disorder that causes inflammation, that is, redness, swelling, heat, and pain.
Dermatologist—A doctor who specializes in skin
care and treatment.
Dermatosis—A noninflammatory skin disorder.
Lesion—An area of abnormal or injured skin.
Malignant—Cancerous.
Pathologist—A person who specializes in studying
diseases. In particular, this person examines the
structural and functional changes in the tissues
and organs of the body that are caused by disease
or that cause disease themselves.

cloths (drapes) may be positioned, and a local anesthetic, usually lidocaine, is injected into the skin near
the lesion. Sometimes the anesthetic contains epinephrine, a drug that helps reduce bleeding during
the biopsy. Sterile gloves and surgical instruments
are always used to reduce the risk of infection.

Aftercare
If stitches have been placed, they should be kept
clean and dry until removed. Stitches are usually
removed five to 10 days after the biopsy. Sometimes
the patient is instructed to put protective ointment on
the stitches before showering. Wounds that have not
been stitched should be cleaned with soap and water
daily until they heal. Adhesive strips should be left in
place for two to three weeks. Pain medications usually
are not necessary.

Risks
Infection and bleeding occur rarely after skin
biopsy. If the skin biopsy may leave a scar, the patient
usually is asked to give informed consent before the test.

Normal results
The biopsy reveals normal skin layers.

Abnormal results
Preparation
The area of the biopsy is cleansed thoroughly with
alcohol or a disinfectant containing iodine. Sterile
3422

The biopsy reveals a noncancerous (benign) or
cancerous (malignant) lesion. Benign lesions may
require treatment.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050.
<http://www.aad.org>.

Collette L. Placek

Skin cancer see Melanoma

Skin cancer, non-melanoma
Definition
Non-melanoma skin cancer is a malignant growth
of the external surface or epithelial layer of the skin.

Description
Skin cancer is the growth of abnormal cells capable of invading and destroying other associated skin
cells. Skin cancer is often subdivided into either melanoma or non-melanoma. Melanoma is a dark-pigmented, usually malignant tumor arising from a skin cell
capable of making the pigment melanin (a melanocyte). Non-melanoma skin cancer most often originates from the external skin surface as a squamous
cell carcinoma or a basal cell carcinoma.
The cells of a cancerous growth originate from a
single cell that reproduces uncontrollably, resulting in
the formation of a tumor. Exposure to sunlight is
documented as the main cause of almost 800,000
cases of non-melanoma skin cancer diagnosed each
year in the United States. The incidence increases for
those living where direct sunshine is plentiful, such as
near the equator.
Basal cell carcinoma affects the skin’s basal layer
and has the potential to grow progressively larger in
size, although it rarely spreads to distant areas (metastasizes). Basal cell carcinoma accounts for 80% of skin
cancers (excluding melanoma), whereas squamous cell
cancer makes up about 20%. Squamous cell carcinoma
is a malignant growth of the external surface of the skin.
Squamous cell cancers metastasize at a rate of 2–6%,
with up to 10% of lesions affecting the ear and lip.

Causes and symptoms
Cumulative sun exposure is considered a significant risk factor for non-melanoma skin cancer. There
GALE ENCYCLOPEDIA OF MEDICINE

is evidence suggesting that early, intense exposure
causing blistering sunburn in childhood may also play
an important role in the cause of non-melanoma skin
cancer. Basal cell carcinoma most frequently affects
the skin of the face, with the next most common sites
being the ears, the backs of the hands, the shoulders,
and the arms. It is prevalent in both sexes and most
commonly occurs in people over 40.
About 1–2% of all skin cancers develop within
burn scars; squamous cell carcinomas account for
about 95% of these cancers, with 3% being basal cell
carcinomas and the remainder malignant melanomas.
Basal cell carcinomas usually appear as small skin
lesions that persist for at least three weeks. This form of
non-melanomatous skin cancer looks flat and waxy,
with the edges of the lesion translucent and rounded.
The edges also contain small fresh blood vessels. An
ulcer in the center of the lesion gives it a dimpled
appearance. Basal cell carcinoma lesions vary from
4–6mm in size, but can slowly grow larger if untreated.
Squamous cell carcinoma also involves skin
exposed to the sun, such as the face, ears, hands, or
arms. This form of non-melanoma is also most common among people over 40. Squamous cell carcinoma
presents itself as a small, scaling, raised bump on the
skin with a crusting ulcer in the center, but without
pain and itching.
Basal cell and squamous cell carcinomas can grow
more easily when people have a suppressed immune
system because they are taking immunosuppressive
drugs or are exposed to radiation. Some people must
take immunosuppressive drugs to prevent the rejection of a transplanted organ or because they have a
disease in which the immune system attacks the body’s
own tissues (autoimmune illnesses); others may need
radiation therapy to treat another form of cancer.
Because of this, everyone taking these immunosuppressive drugs or receiving radiation treatments
should undergo complete skin examination at regular
intervals. If proper treatment is delayed and the tumor
continues to grow, the tumor cells can spread (metastasize) to muscle, bone, nerves, and possibly the brain.

Diagnosis
To diagnose skin cancer, doctors must carefully
examine the lesion and ask the patient about how long
it has been there, whether it itches or bleeds, and other
questions about the patient’s medical history. If skin
cancer cannot be ruled out, a sample of the tissue is
removed and examined under a microscope (a biopsy).
A definitive diagnosis of squamous or basal cell cancer
3423

Skin cancer, non-melanoma

Resources

Skin cancer, non-melanoma

can only be made with microscopic examination of the
tumor cells. Once skin cancer has been diagnosed, the
stage of the disease’s development is determined.
The information from the biopsy and staging allows
the physician and patient to plan for treatment and
possible surgical intervention.

Treatment
A variety of treatment options are available for
those diagnosed with non-melanoma skin cancer.
Some carcinomas can be removed by cryosurgery, the
process of freezing with liquid nitrogen. Uncomplicated
and previously untreated basal cell carcinoma of the
trunk and arms is often treated with curettage and
electrodesiccation, which is the scraping of the lesion
and the destruction of any remaining malignant cells
with an electrical current. Removal of a lesion layer-bylayer down to normal margins (Mohs’ surgery) is an
effective treatment for both basal and squamous cell
carcinoma. Radiation therapy is best reserved for older,
debilitated patients or when the tumor is considered
inoperable. Laser therapy is sometimes useful in specific cases; however, this form of treatment is not widely
used to treat skin cancer.
A newer type of radiation treatment for non-melanoma skin cancers consists of low-energy x rays
delivered through the tip of a portable needle-like
probe at a high dosage rate. This method allows the
radiologist to treat the cancer while sparing the surrounding normal skin. The device was effective in
treating 83% of skin lesions in a group of patients
diagnosed with non-melanomatous skin cancers
during a Phase I trial for the Food and Drug
Administration (FDA). There were no cases of
damage to surrounding tissues.
Some topical (applied onto the skin) creams and
ointments may be used to treat certain types of nonmelanoma skin cancers. For example, imiquimod
cream, a topical immune stimulator, has been shown
effective in treating superficial basal cell carcinoma.
The company who marketed the drug was seeking
FDA approval.

Alternative treatment
Alternative medicine aims to prevent rather than
treat skin cancer. Vitamins have been shown to prevent sunburn and, possibly, skin cancer. Some dermatologists have suggested that taking vitamins E and C
may help prevent sunburn. In one particular study,
men and women took these vitamins for eight days
prior to being exposed to ultraviolet light. The
researchers found that those who consumed vitamins
3424

A close up image of a precancerous mole that could develop
into a melanoma. Melanomas arise from pigment-producing
cells, while non-melanoma skin cancer arises from squamous
cells or basal cells. (Custom Medical Stock Photo. Reproduced
by permission.)

required about 20% more ultraviolet light to induce
sunburn than did people who didn’t take vitamins.
This is the first study that indicates the oral use of
vitamins E and C increases resistance to sunburn.
These antioxidants are thought to reduce the risk of
skin cancer, and are expected to provide protection
from the sun even in lower doses. Other anitoxidant
nutrients, including beta carotene, selenium, zinc, and
the bioflavonoid quercetin have been suggested as
possibly preventing skin cancer. However, a 2003
study reported that selenium was not effective in preventing basal cell carcinoma and may even increase
risk of squamous cell carcinoma and total nonmelanoma skin cancer. Antioxidant herbs such as
bilberry (Vaccinium myrtillus), hawthorn (Crataegus
laevigata), tumeric (Curcuma longa), and ginkgo
(Ginkgo biloba) also have been presented as helpful in
preventing skin cancers.
GALE ENCYCLOPEDIA OF MEDICINE

Autoimmune—Pertaining to an immune response
by the body against one of its own tissues or types of
cells.
Curettage—The removal of tissue or growths by
scraping with a curette.
Dermatologist—A physician specializing in the
branch of medicine concerned with skin.
Electrodesiccation—To make dry, dull, or lifeless
with the use of electrical current.
Lesion—A patch of skin that has been infected or
diseased.
Topical—Referring to a medication or other preparation applied to the skin or the outside of the body.

A team of researchers at Duke University reported
in 2003 that topical application of a combination of
15% vitamin C and 1% vitamin E over a four-day
period offered significant protection against sunburn.
The researchers suggest that this combination may
protect skin against aging caused by sunlight as well.
Another antioxidant that appears to counter the
effects of severe sun exposure is superoxide dismutase,
or SOD. SOD must be given in injectable form, however, because it is destroyed in the digestive tract.
As of 2003, researchers were also looking at botanical compounds that could be added to skin care
products applied externally to lower the risk of skin
cancer. Several botanical compounds had been tested
on animals and found to be effective in preventing skin
cancer, but further research needs to be done in human
subjects.

Prognosis
Both squamous and basal cell carcinoma are curable with appropriate treatment, although basal cell
carcinomas have about a 5% rate of recurrence. Early
detection remains critical for a positive prognosis.
Although it is rare for basal cell carcinomas to metastasize, their metastases can rapidly lead to death if they
invade the eyes, ears, mouth, or the membranes covering the brain.

Prevention
Avoiding exposure to the sun reduces the incidence of non-melanoma skin cancer. Sunscreen with
GALE ENCYCLOPEDIA OF MEDICINE

a sun-protective factor of 15 or higher is helpful in
prevention, along with a hat and clothing to shield the
skin from sun damage. People should examine their
skin monthly for unusual lesions, especially if previous
skin cancers have been experienced.
Advances in photographic technique have now
made it easier to track the development of moles with
the help of whole-body photographs. A growing number of hospitals are offering these photographs as part
of outpatient mole-monitoring services.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Dermatologic Disorders: Malignant Tumors.’’
Section 10, Chapter 126 In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Dermatologic Disorders: Reactions to Sunlight.’’
Section 10, Chapter 119 In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I: Food for Thought. New York: Simon &
Schuster, 2002.
PERIODICALS

Bodner, W. R., B. S. Hilaris, M. Alagheband, et al. ‘‘Use of
Low-Energy X-Rays in the Treatment of Superficial
Nonmelanomatous Skin Cancers.’’ Cancer
Investigation 21 (June 2003): 355–362.
Bray, C. ‘‘The Development of an Improved Method of
Photography for Mole-Monitoring at the University
Hospital of North Durham.’’ Journal of Audiovisual
Media in Medicine 26 (June 2003): 60–66.
Brown, C. K., and J. M. Kirkwood. ‘‘Medical Management
of Melanoma.’’ Surgical Clinics of North America 83
(April 2003): 283–322.
Duffield-Lillico, Anna J., et al. ‘‘Selenium Supplementation
and Secondary Prevention of Nonmelanoma Skin
Cancer in A Randomized Trial.’’ Journal of the National
Cancer Institute 95 (October 1, 2003): 1477-1485.
F’guyer, S., F. Afaq, and H. Mukhtar.
‘‘Photochemoprevention of Skin Cancer by Botanical
Agents.’’ Photodermatology, Photoimmunology and
Photomedicine 19 (April 2003): 56–72.
Jellouli-Elloumi, A., L. Kochbati, S. Dhraief, et al. ‘‘Cancers
Arising from Burn Scars: 62 Cases.’’ [in French] Annales
de dermatologie et de venereologie 130 (April 2003):
413–416.
Lin, J. Y., M. A. Selim, C. R. Shea, et al. ‘‘UV
Photoprotection by Combination Topical Antioxidants
Vitamin C and Vitamin E.’’ Journal of the American
Academy of Dermatology 48 (June 2003): 866-874.

3425

Skin cancer, non-melanoma

KEY TERMS

Skin culture

Spates, S. T., J. R. Mellette, Jr., and J. Fitzpatrick.
‘‘Metastatic Basal Cell Carcinoma.’’ Dermatologic
Surgery 29 (June 2003): 650–652.
Zoler, Mitchell L. ‘‘Imiquimod Up for FDA Approval to
Treat BCC, AK; Phase III Trial Results.’’ Internal
Medicine News 36 (October 1, 2003): 52.
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
Centers for Disease Control and Prevention (CDC). Cancer
Prevention and Control Program. 4770 Buford
Highway, NE, MS K64, Atlanta, GA 30341. (888) 8426355. <http://www.cdc.gov/cancer/comments.htm>.
National Cancer Institute (NCI). NCI Public Inquiries
Office, Suite 3036A, 6116 Executive Boulevard,
MSC8332, Bethesda, MD 20892-8322. (800)
4-CANCER or (800) 332-8615 (TTY).
<http://www.nci.nih.gov>.

Jeffrey P. Larson, RPT
Rebecca J. Frey, PhD
Teresa G. Odle

Skin culture
Definition
A skin culture is a test that is done to identify the
microorganism (bacteria, fungus, or virus) causing a
skin infection and to determine the antibiotic or other
treatment that will effectively treat the infection.

Purpose
Microorganisms can infect healthy skin, but more
often they infect skin already damaged by an injury or
abrasion. Skin infections are contagious and, if left
untreated, can lead to serious complications. A culture
enables a physician to diagnose and treat a skin
infection.

Description
Several groups of microorganisms cause skin
infections: bacteria, fungi (molds and yeast), and
viruses. Based on the appearance of the infection, the
physician determines what group of microorganisms is
likely causing the infection, then he or she collects a
3426

specimen for one or more types of cultures. A sample
of material–such as skin cells, pus, or fluid–is taken
from the infection site, placed in a sterile container,
and sent to the laboratory. In the laboratory, each type
of culture is handled differently.
Bacterial infections are the most common.
Bacteria cause lesions, ulcers, cellulitis, and boils.
Pyoderma are pus-containing skin infections, such as
impetigo, caused by Staphylococcus or group A
Streptococcus bacteria. To culture bacteria, a portion
of material from the infection site is spread over the
surface of a culture plate and placed in an incubator at
body temperature for one to two days. Bacteria in the
skin sample multiply and appear on the plates as
visible colonies. They are identified by noting the
appearance of their colonies, and by performing biochemical tests and a Gram’s stain.
The Gram’s stain is done by smearing part of a
colony onto a microscope slide. After it dries, the slide
is colored with purple and red stains, then examined
under a microscope. The color of stain picked up and
retained by the bacteria (purple or red), their shape
(such as round or rectangle), and their size provide
valuable clues as to their identity.
A sensitivity test, also called antibiotic susceptibility test, is also done. The bacteria are tested against
different antibiotics to determine which will effectively
treat the infection by killing the bacteria.
Fungal cultures are done less frequently. A group
of fungi called dermatophytes cause a skin infection
called ringworm. Yeast causes an infection called
thrush. These infections are usually diagnosed using
a method other than culture, such as the KOH test. A
culture is done only when specific identification of the
mold or yeast is necessary. The specimen is spread on a
culture plate designed to grow fungi, then incubated.
Several different biochemical tests and stains are used
to identify molds and yeasts.
Viruses, such as herpes, can also cause skin infections. Specimens for viral cultures are mixed with
commercially-prepared animal cells in a test tube.
Characteristic changes to the cells caused by the growing virus help identify the virus.
Results for bacterial cultures are usually available
in one to three days. Cultures for fungi and viruses
may take longer–up to three weeks. Cultures are covered by insurance.

Preparation
After cleaning the infected area with sterile saline
and alcohol, the physician collects skin cells, pus, or
GALE ENCYCLOPEDIA OF MEDICINE

Pyoderma—A pus-containing skin infection, such
as impetigo, caused by Staphylococcus or group A
Streptococcus bacteria.
Sensitivity test—A test that determines which antibiotics will treat an infection by killing the bacteria.

fluid using a needle or swab. If necessary, the physician
will open a lesion to collect the specimen. To collect a
specimen for a fungal culture, the physician uses a
scalpel to scrape skin cells into a sterile container.

contract, often resulting in serious scarring; if the
wound is large enough, the scar can actually prevent
movement of limbs. Non-healing wounds, such as
diabetic ulcers, venous ulcers, or pressure sores, can
be treated with skin grafts to prevent infection and
further progression of the wounded area.

Precautions
Skin grafting is generally not used for first- or
second-degree burns, which generally heal with little
or no scarring. Also, the tissue for grafting and the
recipient site must be as sterile as possible to prevent
later infection that could result in failure of the graft.

Description

Normal results
Many types of microorganisms are normally found
on a person’s skin. Presence of these microorganisms
is noted on a skin culture report as ‘‘normal flora.’’

Abnormal results
A microorganism is considered to be a cause of the
infection if it is either the only or predominant microorganism that grew, if it grew in large numbers, or if it
is known to produce infection.
Resources
PERIODICALS

Carroll, John A. ‘‘Common Bacterial
Pyodermas.’’Postgraduate Medicine September 1996:
311-322.

Nancy J. Nordenson

Skin grafting
Definition
Skin grafting is a surgical procedure by which skin
or skin substitute is placed over a burn or non-healing
wound to permanently replace damaged or missing
skin or provide a temporary wound covering.

Purpose
Wounds such as third-degree burns must be covered as quickly as possible to prevent infection or loss
of fluid. Wounds that are left to heal on their own can
GALE ENCYCLOPEDIA OF MEDICINE

The skin is the largest organ of the human body. It
consists of two main layers: the epidermis is the outer
layer, sitting on and nourished by the thicker dermis.
These two layers are approximately 0.04–0.08 in (1–2
mm) thick. The epidermis consists of an outer layer of
dead cells, which provides a tough, protective coating,
and several layers of rapidly dividing cells called
keratinocytes. The dermis contains the blood vessels,
nerves, sweat glands, hair follicles, and oil glands. The
dermis consists mainly of connective tissue, primarily
the protein collagen, which gives the skin its flexibility
and provides structural support. Fibroblasts, which
make collagen, are the main cell type in the dermis.
Skin protects the body from fluid loss, aids in
temperature regulation, and helps prevent disease-causing bacteria or viruses from entering the body. Skin that
is damaged extensively by burns or non-healing wounds
can compromise the health and well-being of the
patient. More than 50,000 people are hospitalized for
burn treatment each year in the United States, and
5,500 die. Approximately 4 million people suffer from
non-healing wounds, including 1.5 million with venous
ulcers and 800,000 with diabetic ulcers, which result
in 55,000 amputations per year in the United States.
Skin for grafting can be obtained from another
area of the patient’s body, called an autograft, if there
is enough undamaged skin available, and if the patient
is healthy enough to undergo the additional surgery
required. Alternatively, skin can be obtained from
another person (donor skin from cadavers is frozen,
stored, and available for use), called an allograft, or
from an animal (usually a pig), called a xenograft.
Allografts and xenografts provide only temporary
covering–they are rejected by the patient’s immune
system within seven to 10 days and must be replaced
with an autograft.
3427

Skin grafting

KEY TERMS

Skin grafting
This skin graft is ready for application. (Photograph by Ted Horowitz, The Stock Market. Reproduced by permission.)

A split-thickness skin graft takes mainly the
epidermis and a little of the dermis, and usually heals
within several days. The wound must not be too deep if
a split-thickness graft is going to be successful, since
the blood vessels that will nourish the grafted tissue
must come from the dermis of the wound itself.
A full-thickness graft involves both layers of the
skin. Full-thickness autografts provide better contour, more natural color, and less contraction at the
grafted site. The main disadvantage of full-thickness
skin grafts is that the wound at the donor site is larger
and requires more careful management; often a
split-thickness graft must be used to cover the donor
site.
A composite skin graft is sometime used, consisting of combinations of skin and fat, skin and cartilage,
or dermis and fat. Composite grafts are used where
three-dimensional reconstruction is necessary. For
example, a wedge of ear containing skin and cartilage
can be used to repair the nose.
Several artificial skin products are available for
burns or non-healing wounds. Unlike allographs and
3428

xenographs, these products are not rejected by the
patient’s body and actually encourage the generation
of new tissue. Artificial skin usually consists of a
synthetic epidermis and a collagen-based dermis.
This artificial dermis, the fibers of which are arranged
in a lattice, acts as a template for the formation of
new tissue. Fibroblasts, blood vessels, nerve fibers,
and lymph vessels from surrounding healthy tissue
cross into the collagen lattice, which eventually
degrades as these cells and structures build a new
dermis. The synthetic epidermis, which acts as a temporary barrier during this process, is eventually
replaced with a split-thickness autograft or with an
epidermis cultured in the laboratory from the
patient’s own epithelial cells. The cost for the
synthetic products in about $1,000 for a 40-in
(100-cm) square piece of artificial skin, in addition
to the costs of the surgery. This procedure is covered
by insurance.

Aftercare
Once a skin graft has been put in place, even after
it has healed, it must be maintained carefully. Patients
GALE ENCYCLOPEDIA OF MEDICINE

Skin grafting

Upper eyelid

Postauricular skin

Preauricular skin
Nasolabial groove
Supraclavicular skin

Skin grafting is a surgical procedure by which skin or a skin substitute is placed over a burn or non-healing wound to replace the
damaged skin or provide a temporary wound covering. Skin for grafting can be obtained from another area of the patient’s body,
such as the face and neck, as shown in the illustration above. (Illustration by Electronic Illustrators Group.)

KEY TERMS
Allograft—Tissue that is taken from one person’s
body and grafted to another person.
Autograft—Tissue that is taken from one part of a
person’s body and transplanted to a different part of
the same person.
Collagen—A protein that provides structural support; the main component of connective tissue.
Dermis—The underlayer of skin, containing blood
vessels, nerves, hair follicles, and oil and sweat
glands.
Epidermis—The outer layer of skin, consisting of a
layer of dead cells that perform a protective function and a second layer of dividing cells.
Fibroblasts—A type of cell found in connective
tissue; produces collagen.
Keratinocytes—Cells found in the epidermis. The
keratinocytes at the outer surface of the epidermis
are dead and form a tough protective layer. The
cells underneath divide to replenish the supply.
Xenograft—Tissue that is transplanted from one
species to another (e.g., pigs to humans).

months, the patient should support the graft with an
Ace bandage or Jobst stocking. Grafts in other areas
of the body should be similarly supported after healing
to decrease the amount of contracture.
Grafted skin does not contain sweat or oil glands,
and should be lubricated daily for two to three months
with a bland oil (e.g., mineral oil) to prevent drying
and cracking.

Risks
The risks of skin grafting include those inherent in
any surgical procedure that involves anesthesia. These
include reactions to the medications, problems breathing, bleeding, and infection. In addition, the risks of an
allograft procedure include transmission of infectious
disease.

Normal results
A skin graft should provide significant improvement in the quality of the wound site, and may prevent
the serious complications associated with burns or
non-healing wounds.

Abnormal results
who have grafts on their legs should remain in bed for
seven to 10 days, with their legs elevated. For several
GALE ENCYCLOPEDIA OF MEDICINE

Failure of a graft can result from poor blood flow,
swelling, or infection.
3429

Skin lesion removal

Resources
ORGANIZATIONS

American Burn Association. 625 N. Michigan Ave., Suite
1530, Chicago, IL 60611. (800) 548-2876.
<http://www.ameriburn.org>.
American Diabetes Association. 1701 North Beauregard
Street, Alexandria, VA 22311. (800) 342-2383.
<http://www.diabetes.org>.

Lisa Christenson, PhD

Skin lesion removal
Definition
Skin lesion removal employs a variety of techniques, from relatively simple biopsies to more complex
surgical excisions, to remove lesions that range from
benign growths to malignant melanoma.

Purpose
Sometimes the purpose of skin lesion removal is to
excise an unsightly mole or other cosmetically unattractive skin growth. Other times, physicians will
remove a skin lesion to make certain it is not cancerous, and, if it proves cancerous, to prevent its spread to
other parts of the body.

Precautions
Most skin lesion removal procedures require few
precautions. The area to be treated is cleaned before
the procedure with alcohol or another antibacterial
preparation, but generally it is not necessary to use a
sterile operating room. Most procedures are performed on an outpatient basis, using a local anesthetic. Some of the more complex procedures may
require specialized equipment available only in an outpatient surgery center. Most of the procedures are not
highly invasive and, frequently, can be well-tolerated
by young and old patients, as well as those with other
medical conditions.

Description
A variety of techniques are used to remove skin
lesions. The particular technique selected will depend
on such factors as the seriousness of the lesion, its
location, and the patient’s ability to tolerate the procedure. Some of the simpler techniques, such as a
3430

biopsy or cryosurgery, can be performed by a primary
care physician. Some of the more complex techniques,
such as excision with a scalpel, electrosurgery, or laser
surgery, are typically performed by a dermatologic
surgeon, plastic surgeon, or other surgical specialist.
Often, the technique selected will depend on how
familiar the physician is with the procedure and how
comfortable he or she is with performing it.
Biopsy
In this procedure, the physician commonly injects
a local anesthetic at the site of the skin lesion, then
removes a sample of the lesion, so that a definite
diagnosis can be made. The sample is sent to a pathology laboratory, where it is examined under a microscope. Certain characteristic skin cells, and their
arrangement in the skin, offer clues to the type of
skin lesion, and whether it is cancerous or otherwise
poses danger. Depending on the results of the microscopic examination, additional surgery may be
scheduled.
A variety of methods are used to obtain a skin
biopsy. The physician may use a scalpel to cut a piece
or remove all of the lesion for examination. Lesions
that are confined to the surface may be sampled with a
shave biopsy, where the physician holds a scalpel blade
parallel to the surface of the skin and slides the blade
across the base of the lesion, removing a sample. Some
physicians use a single-edge razor blade for this,
instead of a scalpel. A physician may also perform a
punch biopsy, in which a small circular punch removes
a plug of skin.
Excision
When excising a lesion, the physician attempts to
remove it completely by using a scalpel to cut the
shape of an ellipse around the lesion. Leaving an
elliptical wound, rather than a circular wound,
makes it easier to insert stitches. If a lesion is suspected
to be cancerous, the physician will not cut directly
around the lesion, but will attempt to also remove a
healthy margin of tissue surrounding it. This is to
ensure that no cancerous cells remain, which would
allow the tumor to reappear. To prevent recurrence of
basal and squamous cell skin cancers, experts recommend a margin of 0.08–0.16 in (2–4 mm) for malignant
melanoma, the margin may be 1.2 in (3 cm) or more.
Destruction
Not all lesions need to be excised. A physician
may simply seek to destroy the lesion using a number
of destructive techniques. These techniques do not
GALE ENCYCLOPEDIA OF MEDICINE







Cryosurgery. This technique employs an extremely
cold liquid or instrument to freeze and destroy
abnormal skin cells that require removal. Liquid
nitrogen is the most commonly used cryogen. It is
typically sprayed on the lesion in several freeze-thaw
cycles to ensure adequate destruction of the lesion.
Curettage. In this procedure, an instrument with a
circular cutting loop at the end is drawn across the
lesion, starting at the middle and moving outward.
With successive strokes, the physician scrapes portions of the lesion away. Sometimes a physician will
use the curet to reduce the size of the lesion before
turning to another technique to finish removing it.
Electrosurgery. This utilizes an alternating current
to selectively destroy skin tissue. Depending on the
type of current and device used, physicians may use
electrosurgical equipment to dry up surface lesions
(electrodessication), to burn off the lesion (electrocoagulation), or to cut the lesion (electrosection).
One advantage of electrosurgery is that it minimizes
bleeding.
Mohs’ micrographic surgery

The real extent of some lesions may not be readily
apparent to the eye, making it difficult for the surgeon
to decide where to make incisions. If some cancer cells
are left behind, for example, the cancer may reappear
or spread. In a technique called Mohs’ micrographic
surgery, surgeons begin by removing a lesion and
examining its margins under a microscope for evidence of cancer. If cancerous cells are found, the surgeon then removes another ring of tissue and examines
the margins again. The process is repeated until the
margins appear clear of cancerous cells. The technique
is considered ideal for aggressive tumors in areas such
as the nose or upper lip, where an excision with wide
margins may be difficult to repair, and may leave a
cosmetically poor appearance.

treat vascular lesions, such as hemangiomas, or pigmented lesions, such as café-au-lait spots.

Preparation
No extensive preparation is required for skin
lesion removal. Most procedures can be performed
on an outpatient basis with a local anesthetic. The
lesion and surrounding area is cleaned with an antibacterial compound before the procedure. A sterile
operating room is not required.

Aftercare
The amount of aftercare will vary, depending on
the skin lesion removal technique. For biopsy, curettage, cryosurgery, and electrosurgery procedures, the
patient is told to keep the wound clean and dry.
Healing will take at least several weeks, and may
take longer, depending on the size of the wound and
other factors. Healing times will also vary with excisions and with Mohs’ micrographic surgery, particularly if a skin graft or skin flap is needed to repair the
resulting wound. Laser surgery may produce changes
in skin coloration that often resolve in time. Pain is
usually minimal following most outpatient procedures, so pain medicines are not routinely prescribed.
Some areas of the body, such as the scalp and fingers,
can be more painful than others, however, and a pain
medicine may be required.

Risks
All surgical procedures present risk of infection.
Keeping the wound clean and dry can minimize the
risk. Antibiotics are not routinely given to prevent
infection in skin surgery, but some doctors believe
they have a role. Other potential complications
include:


bleeding below the skin, which may create a hematoma and sometimes requires the wound to be reopened and drained,



temporary or permanent nerve damage resulting
from excision in an area with extensive and shallow
nerve branches,



wounds that may reopen after they have been
stitched closed, increasing the risk of infection and
scarring.

Lasers
Laser surgery is now applied to a variety of skin
lesions, ranging from spider veins to more extensive
blood vessel lesions called hemangiomas. Until
recently, CO2 lasers were among the more common
laser devices used by physicians, primarily to destroy
skin lesions. Other lasers, such as the Nd:YAG and
flashlamp-pumped pulse dye laser have been developed to achieve more selective results when used to
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Depending on the complexity of the skin lesion
removal procedure, patients can frequently resume
3431

Skin lesion removal

leave sufficient material to be examined by a pathologist, however, and are best used in cases where a visual
diagnosis is certain.

Skin lesions

Description

KEY TERMS
Curet—A surgical instrument with a circular cutting loop at one end. The curet is pulled over the
skin lesion in repeated strokes to remove one portion of the lesion at a time.
Mohs’ micrographic surgery—A surgical technique in which successive rings of skin tissue are
removed and examined under a microscope to
ensure that no cancer is left.
Shave biopsy—A method of removing a sample of
skin lesion so it can be examined by a pathologist.
A scalpel or razor blade is held parallel to the skin’s
surface and is used to slice the lesion at its base.

Skin lesions can be grouped into two categories:
primary and secondary. Primary skin lesions are variations in color or texture that may be present at birth,
such as moles or birthmarks, or that may be acquired
during a person’s lifetime, such as those associated
with infectious diseases (e.g. warts, acne, or psoriasis),
allergic reactions (e.g. hives or contact dermatitis), or
environmental agents (e.g. sunburn, pressure, or temperature extremes). Secondary skin lesions are those
changes in the skin that result from primary skin
lesions, either as a natural progression or as a result
of a person manipulating (e.g. scratching or picking
at) a primary lesion.
The major types of primary lesions are:


their normal routine the day of surgery. Healing frequently will take place within weeks. Some excisions
will require later reconstructive procedures to improve
the appearance left by the original procedure.

Abnormal results


In addition to the complications outlined above, it
is always possible that the skin lesion will reappear,
requiring further surgery.
Resources
ORGANIZATIONS



American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050.
<http://www.aad.org>.
American Society for Dermatologic Surgery. 930 N.
Meacham Road, P.O. Box 4014, Schaumburg, IL
60168-4014. (847) 330-9830.
<http://www.asds-net.org>.
American Society of Plastic and Reconstructive Surgeons.
44 E. Algonquin Rd., Arlington Heights, IL 60005.
(847) 228-9900. <http://www.plasticsurgery.org>.



3432

Pustule. A raised lesion filled with pus. A pustule is
usually the result of an infection, such as acne, imptigeo, or boils.
Papule. A solid, raised lesion less than 2/5 in (1 cm)
across. A patch of closely grouped papules more than
2
/5 in (1 cm) across is called a plaque. Papules and
plaques can be rough in texture and red, pink, or
brown in color. Papules are associated with such
conditions as warts, syphilis, psoriasis, seborrheic
and actinic keratoses, lichen planus, and skin cancer.
Nodule. A solid lesion that has distinct edges and
that is usually more deeply rooted than a papule.
Doctors often describe a nodule as ‘‘palpable,’’
meaning that, when examined by touch, it can be
felt as a hard mass distinct from the tissue surrounding it. A nodule more than 2 cm in diameter is called a
tumor. Nodules are associated with, among other
conditions, keratinous cysts, lipomas, fibromas,
and some types of lymphomas.



Wheal. A skin elevation caused by swelling that can
be itchy and usually disappears soon after erupting.
Wheals are generally associated with an allergic reaction, such as to a drug or an insect bite.

Skin lesions
A skin lesion is a superficial growth or patch
of the skin that does not resemble the area surrounding it.

Vesicle. A raised lesion less than 1/5 in (5 mm) across
and filled with a clear fluid. Vesicles that are more
than 1/5 in (5 mm) across are called bullae or blisters.
These lesions may may be the result of sunburns,
insect bites, chemical irritation, or certain viral infections, such as herpes.



Richard H. Camer

Definition

Macule. A small, circular, flat spot less than 2/5 in
(1 cm) in diameter. The color of a macule is not the
same as that of nearby skin. Macules come in a
variety of shapes and are usually brown, white, or
red. Examples of macules include freckles and flat
moles. A macule more than 2/5 in (1 cm) in diameter is
called a patch.

GALE ENCYCLOPEDIA OF MEDICINE

Telangiectasia. Small, dilated blood vessels that
appear close to the surface of the skin. Telangiectasia
is often a symptom of such diseases as rosacea or
scleroderma.
The major types of secondary skin lesions are:



Ulcer. Lesion that involves loss of the upper portion
of the skin (epidermis) and part of the lower portion
(dermis). Ulcers can result from acute conditions
such as bacterial infection or trauma, or from more
chronic conditions, such as scleroderma or disorders
involving peripheral veins and arteries. An ulcer that
appears as a deep crack that extends to the dermis is
called a fissure.



Scale. A dry, horny build-up of dead skin cells that
often flakes off the surface of the skin. Diseases that
promote scale include fungal infections, psoriasis,
and seborrheic dermatitis.



Crust. A dried collection of blood, serum, or pus.
Also called a scab, a crust is often part of the normal
healing process of many infectious lesions.



Erosion. Lesion that involves loss of the epidermis.



Excoriation. A hollow, crusted area caused by
scratching or picking at a primary lesion.



Scar. Discolored, fibrous tissue that permanently
replaces normal skin after destruction of the dermis.
A very thick and raised scar is called a keloid.



Lichenification. Rough, thick epidermis with exaggerated skin lines. This is often a characteristic of
scratch dermatitis and atopic dermatitis.



Atrophy. An area of skin that has become very thin
and wrinkled. Normally seen in older individuals and
people who are using very strong topical corticosteroid medication.

Causes and symptoms
Skin lesions can be caused by a wide variety of
conditions and diseases. A tendency toward developing
moles, freckles, or birthmarks may be inherited.
Infection of the skin itself by bacteria, viruses, fungi, or
parasites is the most common cause of skin lesions.
Acne, athlete’s foot (tinea pedis), warts, and scabies are
examples of skin infections that cause lesions. Allergic
reactions and sensitivity to outside environmental factors can also lead to the formation of skin lesions.
Underlying conditions can also precipitate the appearance of skin lesions. For example, the decreased sensitivity and poor circulation that accompanies diabetes
mellitus can contribute to the formation of extensive
ulcers on extremities such as the feet. Infections of
body’s entire system can cause the sudden onset of skin
GALE ENCYCLOPEDIA OF MEDICINE

lesions. For example, skin lesions are a hallmark symptom of such diseases as chicken pox, herpes, and small
pox. Cancers affecting the skin, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma,
and Kaposi’s sarcoma, are recognized by their lesions.

Diagnosis
Diagnosis of the underlying cause of skin lesions is
usually based on patient history, characteristics of the
lesion, and where and how it appears on the patient’s
body (e.g. pustules confined to the face, neck and
upper back can indicate acne, while scales appearing
on the scalp and face may indicate seborrheic dermatitis). To determine the cause of an infection, doctors
may also take scrapings or swab samples from lesions
for examination under a microscope or for use in
bacterial, fungal, or viral cultures. In cases where a
fungal infection is suspected, a doctor may examine a
patient’s skin under ultraviolet light using a filter
device called a Woods light–under these conditions,
certain species will taken on specific fluorescent colors.
Dermatologists may also use contrast lighting and
subdued lighting to detect variations in the skin.
When involvement of the immune system is suspected,
doctors may order a immunofluorescence test, which
detects antibodies to specific antigens using a fluorescent chemical. In cases of contact dermatitis, a condition in which a allergic reaction to something irritates
the skin, doctors may use patch tests, in which samples
of specific antigens are introduced into the skin via a
scratch or a needle prick, to determine what substances are provoking the reaction.
The vast majority of skin lesions are noncancerous. However, doctors will determine whether or not a
particular lesion or lesions are cancerous based on
observation and the results of an excisional or punch
biopsy, in which a tissue sample is excised for microscopic analysis. Since early detection is a key to successful treatment, individuals should examine their
skin on a monthly basis for changes to existing
moles, the presence of new moles, or a change in a
certain area of skin. When examining moles, factors to
look for include:


Asymmetry. A normal mole is round, whereas a
suspicious mole is uneven.



Border. A normal mole has a clear-cut border with
the surrounding skin, whereas the edges of a suspect
mole may be irregular.



Color. Normal moles are uniformly tan or brown,
but cancerous moles may appear as mixtures of red,
white, blue, brown, purple, or black.
3433

Skin lesions



Skin lesions

Cyst

Fissure

Macule

Nodule

Papule

Polyp

Pustule

Vesicle

Wheal

A skin lesion is an abnormal growth or an area of skin that does not resemble the skin surrounding it. The illustrations above
feature some of the different types of skin lesions. (Illustration by Electronic Illustrators Group.)



Diameter. Normal moles are usually less than 1/5 in
(5 mm) in diameter, a skin lesion greater than this
may be suspected as cancerous.

Treatment
Treatment of skin lesions depends upon the
underlying cause, what type of lesions they are, and
the patient’s overall health. If the cause of the lesions is
an allergic reaction, removing the allergen from the
patient’s environment is the most effective treatment.
Topical preparations can also be used to clean and
protect irritated skin as well as to remove dead skin
cells and scales. These may come in a variety of forms,
including ointments, creams, lotions, and solutions.
Topical antibiotics, fungicides, pediculicides (agents
that kill lice), and scabicides (agents that kill the scabies parasite) can be applied to treat appropriate skin
infections. Oral medications may be taken to address
systemic infections or conditions. Deeply infected
lesions may require minor surgery to lance and drain
pus. Topical agents to sooth irritated skin and reduce
inflammation may also be applied. Corticosteroids are
3434

particularly effective in reducing inflammation and
itching (puritis). Oatmeal baths, baking soda mixtures,
and calamine lotion are also recommended for the
relief of these symptoms. A type of corticosteroid
may be used to reduce the appearance of keloid
scars. Absorbent powders may also be used to reduce
moisture and prevent the spread of infection. In cases
of ulcers that are slow to heal, pressure dressings may
be used. At times, surgical removal of a lesion may be
recommended–this is the usual course of therapy for
skin cancer. Surgical removal usually involves a simple
excision under local anesthetic, but it may also be
accomplished through freezing (cryotherapy) or laser
surgery.

Prognosis
Skin lesions such as moles, freckles, and birthmarks are a normal part of skin and will not disappear
unless deliberately removed by a surgical procedure.
Lesions due to an allergic reaction often subside soon
after the offending agent is removed. Healing of
lesions due to infections or disorders depends upon
GALE ENCYCLOPEDIA OF MEDICINE

Corticosteroid—A type of steroid medication that
helps relieve itching (puritis) and reduce
inflammation.
Fibroma—A usually benign tumor consisting of
fiborous tissue.
Lesion—A possibly abnormal change or difference
in a tissue or structure, such as the skin.
Lipoma—A usually benign tumor of fatty tissue.
Patch test—Test in which different antigens (substances that cause an allergic reaction) are introduced
into a patient’s skin via a needle prick or scratch and
then observed for evidence of an allergic reaction to
one or more of them. Also known as a scratch test.
Woods light—Device that allows only ultraviolet
light to pass through it.

the type of infection or disorder and the overall health
of the individual. Prognosis for skin cancer primarily
depends upon whether or not the lesion is localized
and whether or not it has spread to other areas of the
body, such as the lymph nodes. In cases where the
lesion is localized and has not spread to other parts
of the body, the cure rate is 95-100%.

Prevention
Not all skin lesions are preventable; moles and
freckles, for example, are benign growths that are
common and unavoidable. However others can be
avoided or minimized by taking certain precautions.
Skin lesions caused by an allergic reaction can be
avoided by determining what the offending agent is
and removing it from the home or workplace, or, if
this is impossible, developing strategies for safely
handling it, such as with gloves and protective clothing. Keeping the skin, nails, and scalp clean and moisturized can help reduce or prevent the incidence of
infectious skin diseases, as can not sharing personal
care items such as combs and make-up with others.
Skin lesions associated with sexually transmitted diseases can be prevented by the use of condoms.
Scratching or picking at existing lesions should be
avoided since this usually serves only to spread infection and may result in scarring. Individuals who have
systemic conditions, such as diabetes mellitus or poor
circulation, that could lead to serious skin lesions
should inspect their bodies regularly for changes in
their skin’s condition. Regular visual inspection of
GALE ENCYCLOPEDIA OF MEDICINE

the skin is also a key to preventing or minimizing the
occurrence of skin cancer, as is the regular use of sun
screens with an SPF of 15 or more.
Resources
BOOKS

Rosen, Theodore, Marilyn B. Lanning, and Marcia J. Hill.
The Nurse’s Atlas of Dermatology. Boston: Little Brown
& Co., 1983.

Bridget Travers

Skin pigmentation disorders
Definition
Skin pigmentation disorders are conditions that
cause the skin to appear lighter or darker than normal,
or blotchy and discolored.

Description
People of all races have skin pigmentation disorders. Some disorders, like albinism (which affects one
out of every 17,000 people) are rare. Others, such as
age spots, are very common.
Skin pigmentation disorders occur because the
body produces either too much or too little melanin, a
pigment that creates hair, skin, and eye color. Melanin
protects the body by absorbing ultraviolet light.
In hypopigmentation means the body does not
produces enough melanin. Albinism, for example, is
an inherited condition that causes a lack of pigment.
So people with albinism typically have light skin, white
or pale yellow hair, and light blue or gray eyes.
Another condition called vitilgo, creates smooth,
depigmented white spots on the skin. Vitilgo affects
nearly 2% of the population, but it strikes people
between 10 and 30 years old more often, and is more
evident in people with darker skin.
In hyperpigmentation, the body produces too
much melanin, causing skin to become darker than
usual. Lichen simplex chronicus is a skin disorder
with severe itching that causes thick, dark patches of
skin to develop. Lamellar ichthyosis (fish scale disease)
is an inherited disease that also is characterized by
darkened, scaly, dry patches of skin.
Hyperpigmentation also occurs in melasma, a
dark mask-like discoloration that covers the cheeks
and bridge of the nose. Melasma can occur during
3435

Skin pigmentation disorders

KEY TERMS

Skin pigmentation disorders

the end of pregnancy. People with the autoimmune
disease (when immune cells, which attack invaders,
become abnormally programed to kill self cells inside
the body) systemic lupus also may develop a similar
butterfly-shaped mask on their faces. In addition,
many people have moles, freckles, age spots, and birthmarks, ranging from red or brown to bluish, black,
covering various parts of their bodies.

Causes and symptoms
Scientists are still studying the reasons why skin
pigmentation disorders occur. In some cases there
are tangible causes, such as sun exposure, drug reactions or genetic inheritance. In other cases, it is not as
clear.
Albinism is an inherited recessive trait. Albinism has
many different forms, but most people who have this
condition have pale skin, hair, and eyes. Melanin also
creates eye color, and serves as a filter that prevents too
much light from entering the eye. Since they lack melanin in their eyes, many people with albinism also have
visual impairment. With little skin pigmentation, they
also sunburn easily and are more prone to skin cancer.
The hypopigmentation spots associated with
vitilgo sometimes form where a person has been cut
or injured. Research has shown that the light patches
associated with vitilgo do not contain melanocytes, the
type of skin cells that create melanin. Some scientists
believe vitilgo may be caused by an autoimmune disorder. It also has been linked to other conditions such
as hyperthyroidism (too much thyroid hormone) and
Addison’s Disease, which affects the adrenal gland.
Hyperpigmentation can be caused by many factors, from too much sunbathing to drug reactions or
poor nutrition. Wounds and scars also can develop
darker patches of skin. A psychological syndrome
gives people with lichen simplex chronicus to develop
a compulsive need to scratch, which causes dark,
leathery skin to form. This can lead to permanent
scarring and infection if untreated. Scientists believe
lamellar ichthyosis is caused by genetics.
The mask caused by melasma may be related to
pregnancy hormones, and usually disappears after a
woman gives birth. Birthmarks, moles, and aging spots
usually are harmless. Some moles, however, can
change in size, color, texture, or start bleeding, which
could indicate possible skin cancer.

Diagnosis
Diagnostic tests vary for different types of skin
pigmentation disorders. Physicians usually can
3436

KEY TERMS
Melanin—A pigment that creates hair, skin and eye
color. Melanin also protects the body by absorbing
ultraviolet light.
Melanocytes— The type of skin cells that create
melanin.
Albinism— An inherited condition that causes a
lack of pigment. People with albinism typically
have light skin, white or pale yellow hair and light
blue or gray eyes
Hypopigmentation—A skin condition that occurs
when the body has too little melanin, or pigment.
Hyperpigmentation— A skin condition that occurs
when the body has too much melanin, or pigment.
Lichen simplex chronicus—A skin disorder with
severe itching that causes thick, dark patches of
skin to develop.
Vitilgo—A skin disorder that creates smooth,
depigmented white spots on the skin.
Lamellar ichthyosis— Also called fish scale disease, this inherited condition is characterized by
darkened, scaly, dry patches of skin.
Melasma—A dark mask-like discoloration that covers the cheeks and bridge of the nose. Also called
‘‘the mask of pregnancy.’’

diagnose albinism by looking carefully at a person’s
hair, skin, and eyes. They may order blood tests and
eye exams as well. A visual exam also is enough to
diagnose vitilgo.
For most hyperpigmentation disorders, doctors
can make a diagnosis by looking at a person’s appearance. To detect conditions like lichen simplex chronicus
or lamellar ichthyosis, or skin cancer, they may also do
a biopsy to remove some of the affected skin for
further study under a microscope. Some physicians
also use a wood’s lamp, or black light test, to diagnose
skin conditions. Affected areas would absorb the
ultraviolet light and stand out with flourescent colors
in the darkened room.

Treatment
For albinism, healthcare providers advise
people to cover up, use sunscreen and avoid
excess sunlight to prevent skin cancer. People
with albinism also must wear protective sunglasses
GALE ENCYCLOPEDIA OF MEDICINE

To treat vitilgo, physicians may prescribe a combination of photo-sensitive medications like trimethylpsoralen and ultraviolet light therapy to
darken the spots. If the person has depigmented
patches covering more than 50% of the body, doctors
also may be able to use skin bleaching agents like
monobenzone to give the skin a lighter, more uniform
appearance. Other options include cosmetic concealers and skin grafting.
Skin-lightening creams are available for hyperpigmentation disorders. Doctors also advise staying
out of the sun. Counseling with a dietitian may help
in cases caused by poor nutrition. For lichen simplex
chronicus, doctors could prescribe antihistamines
and topical steroid creams to stop the itching. If a
mole or birthmark appears suspicious, physicians
often will surgically remove it to prevent skin
cancer.

Prognosis
Most skin pigmentation disorders do not affect a
person’s health, only the outward appearance.

Prevention
In most cases, doctors will recommend using
sunscreen and avoiding too much sun exposure.
Resources
PERIODICALS

Wilson, Tracy. ‘‘The Paler Side of Beauty.’’ Heart and Soul
6, no. 1 (February 1999): 30-33.

Skin resurfacing
Definition
Skin resurfacing employs a variety of techniques
to change the surface texture and appearance of the
skin. Common skin resurfacing techniques include
chemical peels, dermabrasion, and laser resurfacing.

Purpose
Skin resurfacing procedures may be performed
for cosmetic reasons, such as diminishing the appearance of wrinkles around the mouth or eyes. They may
also be used as a medical treatment, such as removing
large numbers of certain precancerous lesions called
actinic keratoses. Physicians sometimes combine techniques, using dermabrasion or laser resurfacing on
some areas of the face, while performing a chemical
peel on other areas.

Precautions
As the popularity of skin resurfacing techniques
has increased, many unqualified or inexperienced providers have entered the field. Patients should choose
their provider with the same degree of care they take
for any other medical procedure. Complications of
skin resurfacing techniques can be serious, including
severe infection and scarring.
Patient’s with active herpesvirus infections are not
good candidates for resurfacing procedures. Persons
who tend to scar easily may also experience poor
results. Patients who have recently used the oral acne
medication isotretinoin (Accutane) may be at higher
risk of scarring following skin resurfacing.

ORGANIZATIONS

Description

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. <http://www.aad.org>.
National Organization for Albinism and Hypopigmentation
(NOAH), 1530 Locust St., #29, Philadelphia, PA,
19102-4415. (800) 473-2310.
<http://www.albinism.org>.

Chemical peel

OTHER

MelanomaNet. <http://www.skincarephysicians.com/
melanomanet/index.html>.
National Weather Service. ‘‘Ultraviolet Light Index.’’
<http://www.nws.noaa.gov/pa/secnews/
uv/index.html>.

Melissa Knopper
GALE ENCYCLOPEDIA OF MEDICINE

Chemical peels employ a variety of caustic chemicals to selectively destroy several layers of skin. The
peeling solutions are ‘‘painted on,’’ area-by-area, to
ensure that the entire face is treated. After the skin
heals, discoloration, wrinkles, and other surface irregularities are often eliminated.
Chemical peels are divided into three types: superficial, medium-depth, and deep. The type of peel
depends on the strength of the chemical used, and on
how deeply it penetrates. Superficial peels are used for
fine wrinkles, sun damage, acne, and rosacea. The
medium-depth peel is used for more obvious wrinkles
and sun damage, as well as for precancerous lesions
3437

Skin resurfacing

and, in some cases, prescription corrective lenses.
Surgery may be necessary to correct visual
impairments.

Skin resurfacing

like actinic keratoses. Deep peels are used for the most
severe wrinkling and sun damage.

anesthesia, but local anesthetics combined with intravenous sedatives are frequently sufficient to control
pain.

Dermabrasion
Dermabrasion uses an abrasive tool to selectively
remove layers of skin. Some physicians use a handheld motorized tool with a small wire brush or diamond-impregnated grinding wheel at the end. Other
physicians prefer to abrade the skin by hand with an
abrasive pad or other instrument. Acne scarring is one
of the prime uses for dermabrasion. It also can be used
to treat wrinkling, remove surgical scars, and obliterate tattoos.
Laser resurfacing
Laser resurfacing is the most recently developed
technique for skin resurfacing. Specially designed,
pulsed CO2 lasers can vaporize skin layer-by-layer,
causing minimal damage to other skin tissue. Special
scanning devices move the laser light across the skin in
predetermined patterns, ensuring proper exposure.
Wrinkling around the eyes, mouth, and cheeks are
the primary uses for laser resurfacing. Smile lines or
those associated with other facial muscles tend to
reappear after laser resurfacing. Laser resurfacing
appears to achieve its best results as a spot treatment;
patients expecting complete elimination of their wrinkles will not be satisfied.

Preparation
Chemical peel
Preparation for the chemical peel begins several
weeks before the actual procedure. To promote turnover of skin cells, patients use a mild glycolic acid
lotion or cream in the morning, and the acne cream
tretinoin in the evening. They also use hydroquinone
cream, a bleaching product that helps prevent later
discoloration. To prevent reappearance of a herpes
simplex virus infection, antiviral medicine is started a
few days before the procedure and continues until the
skin has healed.
Patients arrive for the procedure wearing no
makeup. The physician ‘‘degreases’’ the patient’s face
using alcohol or another cleanser. Some degree of pain
accompanies all types of peels. For a superficial peel,
use of a hand held fan to cool the face during the
procedure is often sufficient. For medium-depth
peels, the patient may take a sedative or aspirin.
During the procedure, cold compresses and a handheld fan can also reduce pain. Deep peels can be
extremely painful. Some physicians prefer general
3438

Dermabrasion
Dermabrasion does not require much preparation. It is usually performed under local anesthesia,
although some physicians use intravenous sedation or
general anesthesia. The physician begins by marking
the areas to be treated and then chilling them with ice
packs. In order to stiffen the skin, a spray refrigerant is
applied to the area, which also helps control pain.
Some physicians prefer to inject the area with a solution of saline and local anesthetic, which also leaves
the skin’s surface more solid. Since dermabrasion can
cause quite a bit of bleeding, physicians and their
assistants will wear gloves, gowns, and masks to protect themselves from possible blood-transmitted
infection.
Laser resurfacing
Antiviral medications should be started several
days before the procedure. Laser resurfacing is performed under local anesthesia. An oral sedative may
also be taken. The patient’s eyes must be shielded, and
the area surrounding the face should be shielded with
wet drapes or crumpled foil to catch stray beams of
laser light. The physician will mark the areas to be
treated before beginning the procedure.

Aftercare
Chemical peel
Within a day or so following a superficial peel, the
skin will turn faint pink or brown. Over the next few
days, dead skin will peel away. Patients will be
instructed to wash their skin frequently with a mild
cleanser and cool water, then apply an ointment to the
skin to keep it moist. After a medium-depth peel, the
skin turns deep red or brown, and crusts may form.
Care is similar to that following a superficial peel.
Redness may persist for a week or more. Deep-peeled
skin will turn brown and crusty. There may also be
swelling and some oozing of fluid. Frequent washing
and ointments are favored over dressings. The skin
typically heals in about two weeks, but redness may
persist.
Dermabrasion
Following the procedure, an ointment may be
applied, and the wound will be covered with a dressing
and mask. Patients with a history of herpesvirus
GALE ENCYCLOPEDIA OF MEDICINE

Actinic keratosis—A crusty, scaly skin lesion,
caused by exposure to the sun, which can transform
into skin cancer.
Herpesviruses—A family of viruses responsible for
cold sores, chicken pox, and genital herpes.
Isotretinoin—A powerful vitamin A derivative used
in the treatment of acne. It can promote scarring
after skin resurfacing procedures.

infections will begin taking an antiviral medication to
prevent a recurrence. After 24 hours, the dressing is
removed, and ointment is reapplied to keep the wound
moist. Patients are encouraged to wash their face with
plain water and reapply ointment every few hours.
This relieves itching and pain and helps remove oozing
fluid and other matter. Patients may require a pain
medication. A steroid medication may be taken during
the first few days to reduce swelling. The skin will take
a week or more to heal, but may remain very red.
Laser resurfacing
The skin should be kept moist following laser
resurfacing. This promotes more rapid healing and
reduces the risk of infection. Some physicians favor
application of ointments only to the skin; others prefer
the use of dressings. In either case, care of the skin is
similar to that given following a chemical peel. The
face is washed with plain water to remove ooze, and an
ointment is reapplied. Healing will take approximately
two weeks. Pain medications and a steroid to reduce
swelling may also be taken.

Risks
All resurfacing procedures can lead to infection
and scarring. It is also possible that skin coloration
will be altered, or that redness of the skin will be
prolonged for many months. Some of the peeling
agents used in deep chemical peels can affect the function of the heart.

Normal results
Depending on the resurfacing techniques selected,
it is possible to improve the appearance of skin
damaged by sun, age, or disease in many people.
Skin resurfacing techniques address only the surface
of the skin; procedures such as face-lift surgery or
GALE ENCYCLOPEDIA OF MEDICINE

blepharoplasty may be needed to repair other agerelated skin changes. All resurfacing procedures are
accompanied by some pain, redness, and skin color
changes. These may persist for several months following the procedure, but they usually resolve over time.

Abnormal results
As noted above, resurfacing procedures can reactivate herpesvirus infections or lead to new, sometimes
serious infections. All resurfacing techniques intentionally create skin wounds, creating the possibility
for scarring. Abnormal results such as these can be
minimized with use of antiviral medications prior to
the procedure and good wound care afterward.
Selection of an experienced, reputable provider also
is key.
Resources
ORGANIZATIONS

American Society for Dermatologic Surgery. 930 N.
Meacham Road, P.O. Box 4014, Schaumburg, IL
60168-4014. (847) 330-9830. <http://www.asdsnet.org>.
American Society for Laser Medicine and Surgery. 2404
Stewart Square, Wausau, WI 54401.(715) 845-9283.
<http://www.aslms.org>.
American Society of Plastic and Reconstructive Surgeons.
44 E. Algonquin Rd., Arlington Heights, IL 60005.
(847) 228-9900. <http://www.plasticsurgery.org>.

Richard H. Camer

Skin traction see Traction; Immobilization

Skull x rays
Definition
Skull x rays are performed to examine the nose,
sinuses, and facial bones. These studies may also be
referred to as sinus x rays. X-ray studies produce films,
also known as radiographs, by aiming x rays at soft
bones and tissues of the body. X-ray beams are similar
to light waves, except their shorter wavelength allows
them to penetrate dense substances, producing images
and shadows on film.

Purpose
Doctors may order skull x rays to aid in the diagnosis of a variety of diseases or injuries.
3439

Skull x rays

KEY TERMS

Skull x rays

Sinusitis
Sinus x rays may be ordered to confirm a diagnosis of sinusitis, or sinus infection.
Fractures
A skull x ray may detect bone fractures resulting
from injury or disease. The skull x ray should clearly
show the skull cap, jaw bones, and facial bones.
Tumors
Skull radiographs may indicate tumors in facial
bones, tissues, or the sinuses. Tumors may be benign
(not cancerous) or malignant (cancerous).
Other
Birth defects (referred to as congenital anomalies)
may be detected on a skull x ray by changes in bone
structure. Abnormal tissues or glands resulting from
various conditions or diseases may also be shown on a
skull radiograph.

Precautions
As with any x-ray procedure, women who may be
pregnant are advised against having a skull x ray if it is
not absolutely necessary. However, a lead apron may
be worn across the abdomen during the procedure to
protect the fetus. Children are also more sensitive to
x-ray exposure. Children of both sexes should wear a
protective covering (a lead apron) in the genital/reproductive area. In general, skull x-ray exposure is minimal and x-ray equipment and procedures are
monitored to ensure radiation safety.

Description
Skull or sinus x rays may be performed in a doctor’s office that has x-ray equipment and a technologist available. The exam may also be performed in an
outpatient radiology facility or a hospital radiology
department.
In many instances, particularly for sinus views,
the patient will sit upright in a chair, perhaps with
the head held stable by a foam vise. A film cassette is
located behind the patient. The x-ray tube is in front of
the patient and may be moved to allow for different
positions and views. A patient may also be asked to
move his or her head at various angles and positions.
In some cases, technologists will ask the patient to
lie on a table and will place the head and neck at
various angles. In routine skull x rays, as many as
3440

A skull x ray. (Photo Researchers. Reproduced by permission.)

five different views may be taken to allow a clear
picture of various bones and tissues. The length of
the test will vary depending on the number of views
taken, but in general, it should last about 10 minutes.
The technologist will usually ask a patient to wait
while the films are being developed to ensure that
they are clear before going to the radiologist.

Preparation
There is no preparation for the patient prior to
arriving at the radiology facility. Patients will be asked
to remove jewelry, dentures, or other metal objects
that may produce artifacts on the film. The referring
doctor or x-ray technologist can answer any questions
regarding the procedure. Any woman who is, or may
be, pregnant should tell the technologist.

Aftercare
There is no aftercare required following skull or
sinus x-ray procedures.

Risks
There are no common side effects from skull or
sinus x ray. The patient may feel some discomfort in
GALE ENCYCLOPEDIA OF MEDICINE

Radiograph—The actual picture or film produced
by an x-ray study.
X ray—A form of electromagnetic radiation with
shorter wavelengths than normal light. X rays can
penetrate most structures.

the positioning of the head and neck, but will have no
complications. Any x-ray procedure carries minimal
radiation risk, and children and pregnant women
should be protected from radiation exposure to the
abdominal or genital areas.

Normal results
Normal results should indicate sinuses, bones,
tissues, and other observed areas are of normal size,
shape, and thickness for the patient’s age and medical
history. Results, whether normal or abnormal, will be
provided to the referring doctor in a written report.

Abnormal results
Abnormal results may include:
Sinusitis
Air in sinuses will show up on a radiograph as
black, but fluid will be cloudy or white (opaque). This
helps the radiologist to identify trapped fluids in the
sinuses. In chronic sinusitis, the radiologist may also
note thickening or hardening of the bony wall of an
infected sinus.
Fractures
Radiologists may recognize even tiny facial bone
fractures as a line of defect.
Tumors
Tumors may be visible if the bony sinus wall is
distorted or destroyed. Abnormal findings may result
in follow-up imaging studies.
Other
Skull x rays may also detect disorders that show
up as changes in bone structure, such as Paget’s disease of the bone or acromegaly (a disorder associated
with excess growth hormones from the pituitary
gland). Areas of calcification, or gathering of calcium
GALE ENCYCLOPEDIA OF MEDICINE

deposits, may indicate a condition such as an infection
of bone or bone marrow (osteomyelitis).
Resources
ORGANIZATIONS

National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
National Head Injury Foundation, Inc. (888) 222-5287.
<http://www.nhif.org/home.html>.
Radiological Society of North America. 820 Jorie
Boulevard, Oak Brook, IL 60523-2251. (630) 571-2670.
<http://www.rsna.org>.

Teresa Odle

SLE see Systemic lupus erythematosus

Sleep apnea
Definition
Sleep apnea is a condition in which breathing
stops for more than ten seconds during sleep. Sleep
apnea is a major, though often unrecognized, cause of
daytime sleepiness. It can have serious negative effects
on a person’s quality of life, and is thought to be
considerably underdiagnosed in the United States.

Description
A sleeping person normally breathes continuouusly and uninterruptedly throughout the night.
A person with sleep apnea, however, has frequent
episodes (up to 400–500 per night) in which he or she
stops breathing. This interruption of breathing is
called ‘‘apnea.’’ Breathing usually stops for about 30
seconds; then the person usually startles awake with a
loud snort and begins to breathe again, gradually falling back to slep.
There are two forms of sleep apnea. In obstructive
sleep apnea (OSA), breathing stops because tissue in
the throat closes off the airway. In central sleep apnea,
(CSA), the brain centers responsible for breathing fail
to send messages to the breathing muscles. OSA is
much more common than CSA. It is thought that
about 1–10% of adults are affected by OSA; only
about one tenth of that number have CSA. OSA can
affect people of any age and of either sex, but it is most
common in middle-aged, somewhat overweight men,
especially those who use alcohol.
3441

Sleep apnea

KEY TERMS

Sleep apnea

Causes and symptoms
Obstructive sleep apnea
Obstructive sleep apnea occurs when part of the
airway is closed off (usually at the back of the throat)
while a person is trying to inhale during sleep. People
whose airways are slightly narrower than average are
more likely to be affected by OSA. Obesity, especially
obesity in the neck, can increase the risk of developing
OSA, because the fat tissue tends to narrow the airway.
In some people, the airway is blocked by enlarged
tonsils, an enlarged tongue, jaw deformities, or growths
in the neck that compress the airway. Blocked nasal
passages may also play a part in some people.
When a person begins to inhale, the expansion of
the lungs lowers the air pressure inside the airway. If
the muscles that keep the airway open are not working
hard enough, the airway narrows and may collapse,
shutting off the supply of air to the lungs. OSA occurs
during sleep because the neck muscles that keep the
airway open are not as active then. Congestion in the
nose can make collapse more likely, since the extra
effort needed to inhale will lower the pressure in the
airway even more. Drinking alcohol or taking tranquilizers in the evening worsens this situation, because
these cause the neck muscles to relax. (These drugs
also lower the ‘‘respiratory drive’’ in the nervous system, reducing breathing rate and strength.)
People with OSA almost always snore heavily,
because the same narrowing of the airway that causes
snoring can also cause OSA. Snoring may actually help
cause OSA as well, because the vibration of the throat
tissues can cause them to swell. However, most people
who snore do not go on to develop OSA.
Other risk factors for developing OSA include
male sex; pregnancy; a family history of the disorder;
and smoking. With regard to gender, it has been found
that male sex hormones sometimes cause changes in
the size or structure of the upper airway. The weight
gain that accompanies pregnancy can affect a
woman’s breathing patterns during sleep, particularly
during the third trimester. With regard to family history, OSA is known to run in families even though no
gene or genes associated with the disorder have been
identified as of 2002. Smoking increases the risk of
developing OSA because it causes inflammation, swelling, and narrowing of the upper airway.
Some patients being treated for head and neck
cancer develop OSA as a result of physical changes in
the muscles and other tissues of the neck and throat.
Doctors recommend prompt treatment of the OSA to
improve the patient’s quality of life.
3442

Central sleep apnea
In central sleep apnea, the airway remains open,
but the nerve signals controlling the respiratory muscles are not regulated properly. This can cause wide
fluctuations in the level of carbon dioxide (CO2) in the
blood. Normal activity in the body produces CO2,
which is brought by the blood to the lungs for exhalation. When the blood level of CO2 rises, brain centers
respond by increasing the rate of respiration, clearing
the CO2. As blood levels fall again, respiration slows
down. Normally, this interaction of CO2 and breathing rate maintains the CO2 level within very narrow
limits. CSA can occur when the regulation system
becomes insensitive to CO2 levels, allowing wide fluctuations in both CO2 levels and breathing rates. High
CO2 levels cause very rapid breathing (hyperventilation), which then lowers CO2 so much that breathing
becomes very slow or even stops. CSA occurs during
sleep because when a person is awake, breathing is
usually stimulated by other signals, including conscious awareness of breathing rate.
A combination of the two forms is also possible,
and is called mixed sleep apnea. Mixed sleep apnea
episodes usually begin with a reduced central respiratory drive, followed by obstruction.
OSA and CSA cause similar symptoms. The most
common symptoms are:


daytime sleepiness



morning headaches



a feeling that sleep is not restful



disorientation upon waking



poor judgment



personality changes

Sleepiness is caused not only by the frequent interruption of sleep, but by the inability to enter long
periods of deep sleep, during which the body performs
numerous restorative functions. OSA is one of the
leading causes of daytime sleepiness, and is a major
risk factor for motor vehicle accidents. Headaches and
disorientation are caused by low oxygen levels during
sleep, from the lack of regular breathing.
Other symptoms of sleep apnea may include sexual dysfunction, loss of concentration, memory loss,
intellectual impairment, and behavioral changes
including anxiety and depression.
Sleep apnea is also associated with night sweats
and nocturia, or increased frequency of urination at
night. Bedwetting in children is also linked to sleep
apnea.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Excessive daytime sleepiness is the complaint that
usually brings a person to see the doctor. A careful
medical history will include questions about alcohol or
tranquilizer use, snoring (often reported by the person’s partner), and morning headaches or disorientation. A physical exam will include examination of the
throat to look for narrowing or obstruction. Blood
pressure is also measured. Measuring heart rate or
blood levels of oxygen and CO2 during the daytime
will not usually be done, since these are abnormal only
at night in most patients.
In some cases the person’s dentist may suggest the
diagnosis of OSA on the basis of a dental checkup or
evaluation of the patient for oral surgery.
Confirmation of the diagnosis usually requires
making measurements while the person sleeps. These
tests are called a polysomnography study, and are conducted during an overnight stay in a specialized sleep
laboratory. Important parts of the polysomnography
study include measurements of:


heart rate



airflow at the mouth and nose



respiratory effort



sleep stage (light sleep, deep sleep, dream sleep, etc.)



oxygen level in the blood, using a noninvasive probe
(ear oximetry)

Simplified studies done overnight at home are also
possible, and may be appropriate for people whose
profile strongly suggests the presence of obstructive
sleep apnea; that is, middle-aged, somewhat overweight men, who snore and have high blood pressure.
The home-based study usually includes ear oximetry
and cardiac measurements. If these measurements
GALE ENCYCLOPEDIA OF MEDICINE

support the diagnosis of OSA, initial treatment is
usually suggested without polysomnography. Homebased measurements are not used to rule out OSA,
however, and if the measurements do not support the
OSA diagnosis, polysomnography may be needed to
define the problem further.
Both types of studies are usually covered by insurance with the appropriate referral from a physician.
Without insurance, lab-based polysomnography cost
approximately $1,500 in 1997, while overnight home
monitoring cost between $500 and $1,000.

Treatment
Behavioral changes
Treatment of obstructive sleep apnea begins with
reducing the use of alcohol or tranquilizers in the
evening, if these have been contributing to the problem. Weight loss is also effective, but if the weight
returns, as it often does, so does the apnea. Changing
sleeping position may be effective; snoring and sleep
apnea are both most common when a person sleeps on
his back. Turning to sleep on the side may be enough
to clear up the symptoms. Raising the head of the bed
may also help. Opening of the nasal passages can
provide some relief. There are a variety of nasal
devices such as clips, tapes, or holders which may
help, though discomfort may limit their use. Nasal
decongestants may be useful, but should not be taken
for sleep apnea without the consent of the treating
physician.
Oxygen and drug therapy
Supplemental nighttime oxygen can be useful for
some people with either central and obstructive sleep
apnea. Tricyclic antidepressant drugs such as protriptyline (Vivactil) may help by increasing the muscle
tone of the upper airway muscles, but their side effects
may severely limit their usefulness.
Mechanical ventilation
For moderate to severe sleep apnea, the most
successful treatment is nighttime use of a ventilator,
called a CPAP machine. CPAP (continuous positive
airway pressure) blows air into the airway continuously, preventing its collapse. CPAP requires the use
of a nasal mask. The appropriate pressure setting for
the CPAP machine is determined by polysomnography in the sleep lab. Its effects are dramatic; daytime
sleepiness usually disappears within one to two days
after treatment begins. CPAP is used to treat both
obstructive and central sleep apnea.
3443

Sleep apnea

Sleep apnea can also cause serious changes in the
cardiovascular system. Daytime hypertension (high
blood pressure) is common. An increase in the number
of red blood cells (polycythemia) is possible, as is an
enlarged left ventricle of the heart (cor pulmonale), and
left ventricular failure. In some people, sleep apnea
causes life-threatening changes in the rhythm of the
heart, including heartbeat slowing (bradycardia),
racing (tachycardia), and other types of ‘‘arrhythmias.’’ Sudden death may occur from such arrhythmias. Patients with the Pickwickian syndrome (named
after a Charles Dickens character) are obese and
sleepy, with right heart failure, pulmonary hypertension, and chronic daytime low blood oxygen (hypoxemia) and increased blood CO2 (hypercapnia).

Sleep apnea

CPAP is tolerated well by about two-thirds of
patients who try it. Bilevel positive airway pressure
(BiPAP), is an alternative form of ventilation. With
BiPAP, the ventilator reduces the air pressure when
the person exhales. This is more comfortable for some.
Surgery
Surgery can be used to correct obstructions in the
airways. The most common surgery is called UPPP,
for uvulopalatopharngyoplasty. This surgery removes
tissue from the rear of the mouth and top of the throat.
The tissues removed include parts of the uvula (the
flap of tissue that hangs down at the back of the
mouth), the soft palate, and the pharynx. Tonsils and
adenoids are usually removed in this operation. This
operation significantly improves sleep apnea in
slightly more than half of all cases.

KEY TERMS
Continuous positive airway pressure (CPAP)—A
ventilation system that blows a gentle stream of
air into the nose to keep the airway open.
Genioplasty—An operation performed to reshape
the chin. Genioplasties are often done to treat OSA
because the procedure changes the structure of the
patient’s upper airway.
Mandible—The medical term for the lower jaw.
One type of oral appliance used to treat OSA
pushes the mandible forward in order to ease
breathing during sleep.
Nocturia—Excessive need to urinate at night.
Nocturia is a symptom of OSA and often increases
the patient’s daytime sleepiness.

Reconstructive surgery is possible for those whose
OSA is due to constriction of the airway by lower jaw
deformities. Genioplasty, which is a procedure that
plastic surgeons usually perform to reshape a patient’s
chin to improve his or her appearance, is now being
done to reshape the upper airway in patients with OSA.

Polysomnography—A group of tests administered
to analyze heart, blood, and breathing patterns
during sleep.
Tracheotomy—A surgical procedure in which a
small hole is cut into the trachea, or windpipe,
below the level of the vocal cords.

When other forms of treatment are not successful,
obstructive sleep apnea may be treated by a tracheostomy. In this procedure, an opening is made into the
trachea (windpipe) below the obstruction, and a tube
inserted to maintain an air passage. A tracheostomy
requires a great deal of care to prevent infection of the
tracheostomy site. In addition, since air is no longer
being filtered and moistened by the nasal passages
before entering the lungs, the lower airways can
become dry and susceptible to infection as well.
Tracheostomy is usually reserved for those whose
apnea has led to life-threatening heart arrhythmias,
and who have not been treated successfully with
other treatments.

Uvulopalatopharyngoplasty (UPPP)—An operation to remove excess tissue at the back of the throat
to prevent it from closing off the airway during sleep.

Oral appliances
Another approach to treating OSA involves the
use of oral appliances intended to improve breathing
either by holding the tongue in place or by pushing the
lower jaw forward during sleep to increase the air
volume in the upper airway. The first type of oral
appliance is known as a tongue retaining device or
TRD. The second type is variously called an oral
protrusive device (OPD) or mandibular advancement
splint (MAS), because it holds the mandible, or lower
jaw, forward during sleep. These oral devices appear
to work best for patients with mild-to-moderate OSA,
and in some cases can postpone or prevent the need for
surgery. Their rate of patient compliance is about
3444

50%; most patients who stop using oral appliances
do so because their teeth are in poor condition.
TRDs and OPDs can be fitted by dentists; however,
most dentists work together with the patient’s physician following a polysomnogram rather than prescribing the device by themselves.

Prognosis
The combination of behavioral changes, ventilation assistance, drug therapy, and surgery allow most
people with sleep apnea to be treated successfully,
although it may take some time to determine the
most effective and least intrusive treatment.
Polysomnography testing is usually required after
beginning a treatment to determine how effective it
has been.

Prevention
For people who snore frequently, weight control,
avoidance of evening alcohol or tranquilizers, and
adjustment of sleeping position may help reduce the
risk of developing obstructive sleep apnea.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disorders of the Oral Region.’’ Section 9, Chapter 105
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Sleep Disorders.’’ Section 14, Chapter 173 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Chasens, E. R., and M. G. Umlauf. ‘‘Nocturia: A Problem
That Disrupts Sleep and Predicts Obstructive Sleep
Apnea’’ Geriatric Nursing 24 (March-April 2003):
76–81, 105.
Chung, S. A., S. Jairam, M. R. Hussain, and C. M. Shapiro.
‘‘How, What, and Why of Sleep Apnea. Perspectives for
Primary Care Physicians.’’ Canadian Family Physician
48 (June 2002): 1073–1080.
Edwards, N., P. G. Middleton, D. M. Blyton, and C. E.
Sullivan. ‘‘Sleep Disordered Breathing and Pregnancy.’’
Thorax 57 (June 2002): 555–558.
Hisanaga, A., T. Itoh, Y. Hasegawa, et al. ‘‘A Case of Sleep
Choking Syndrome Improved by the Kampo Extract of
Hange-Koboku-To.’’ Psychiatry and Clinical
Neuroscience 56 (June 2002): 325–327.
Kapur, V., K. P. Strohl, S. Redline, et al. ‘‘Underdiagnosis
of Sleep Apnea Syndrome in U.S. Communities.’’ Sleep
and Breathing 6 (June 2002): 49–54.
Koliha, C. A. ‘‘Obstructive Sleep Apnea in Head and Neck
Cancer Patients Post Treatment ... Something to
Consider?’’ ORL—Head and Neck Nursing 21 (Winter
2003): 10–14.
Neill, A., R. Whyman, S. Bannan, et al. ‘‘Mandibular
Advancement Splint Improves Indices of Obstructive
Sleep Apnoea and Snoring but Side Effects Are
Common.’’ New Zealand Medical Journal 115 (June 21,
2002): 289–292.
Rose, E., R. Staats, J. Schulte-Monting, et al. ‘‘Long-Term
Compliance with an Oral Protrusive Appliance in
Patients with Obstructive Sleep Apnoea.’’ [in German]
Deutsche medizinische Wochenschrift 127 (June 7, 2002):
1245–1249.
Shiomi, T., A. T. Arita, R. Sasanabe, et al. ‘‘Falling Asleep
While Driving and Automobile Accidents Among
Patients with Obstructive Sleep Apnea-Hypopnea
Syndrome.’’ Psychiatry and Clinical Neuroscience 56
(June 2002): 333–334.
Stanton, D. C. ‘‘Genioplasty.’’ Facial Plastic Surgery 19
(February 2003): 75–86.
Umlauf, M. G., and E. R. Chasens. ‘‘Bedwetting—Not
Always What It Seems: A Sign of Sleep-Disordered
Breathing in Children.’’ Journal for Specialists in
Pediatric Nursing 8 (January-March 2003): 22–30.
Veale, D., G. Poussin, F. Benes, et al. ‘‘Identification of
Quality of Life Concerns of Patients with Obstructive
GALE ENCYCLOPEDIA OF MEDICINE

Sleep Apnoea at the Time of Initiation of Continuous
Positive Airway Pressure: A Discourse Analysis.’’
Quality of Life Research 11 (June 2002): 389–399.
Viera, A. J., M. M. Bond, and S. J. Yates. ‘‘Diagnosing
Night Sweats.’’ American Family Physician 67 (March
1, 2003): 1019–1024.
ORGANIZATIONS

American Academy of Otolaryngology, Head and Neck
Surgery, Inc. One Prince Street, Alexandria, VA 223143357. (703) 836-4444. <http://www.entnet.org>.
American Dental Association. 211 East Chicago Avenue,
Chicago, IL 60611. (312) 440-2500. <www.ada.org>.
American Sleep Apnea Association. 1424 K Street NW,
Suite 302, Washington, DC 20005. (202) 293-3650. Fax:
(202) 293-3656. <www.sleepapnea.org>.
Canadian Coordinating Office for Health Technology
Assessment. <www.ccohta.ca/pubs/english/sleep/
treatmnt>.
National Sleep Foundation. 1522 K Street, NW, Suite 500,
Washington, DC 20005.
<www.sleepfoundation.org>.
OTHER

American Sleep Apnea Association (ASAA). Considering
Surgery for Snoring? <http://www.sleepapnea.org/
snoring.html>.
National Heart, Lung, and Blood Institute (NHLBI). Facts
About Sleep Apnea. NIH Publication No. 95-3798.
<http://www.nhlbi.nih.gov/health/public/
sleep/sleepapn.htm>.

Richard Robinson
Rebecca J. Frey, PhD

Sleep disorders
Definition
Sleep disorders are a group of syndromes characterized by disturbance in the patient’s amount of sleep,
quality or timing of sleep, or in behaviors or physiological conditions associated with sleep. There are
about 70 different sleep disorders. To qualify for the
diagnosis of sleep disorder, the condition must be a
persistent problem, cause the patient significant emotional distress, and interfere with his or her social or
occupational functioning.
Although sleep is a basic behavior in animals as
well as humans, researchers still do not completely
understand all of its functions in maintaining health.
In the past 30 years, however, laboratory studies on
human volunteers have yielded new information
about the different types of sleep. Researchers have
3445

Sleep disorders

Resources

Sleep disorders

learned about the cyclical patterns of different types of
sleep and their relationships to breathing, heart rate,
brain waves, and other physical functions. These measurements are obtained by a technique called
polysomnography.

prescription medications, substance abuse, or medical
conditions. The two major categories of primary sleep
disorders are the dyssomnias and the parasomnias.

There are five stages of human sleep. Four stages
have non-rapid eye movement (NREM) sleep, with
unique brain wave patterns and physical changes
occurring. Dreaming occurs in the fifth stage, during
rapid eye movement (REM) sleep.

Dyssomnias are primary sleep disorders in which
the patient suffers from changes in the amount, restfulness, and timing of sleep. The most important dyssomnia is primary insomnia, which is defined as
difficulty in falling asleep or remaining asleep that
lasts for at least one month. It is estimated that 35%
of adults in the United States experience insomnia
during any given year, but the number of these adults
who are experiencing true primary insomnia is
unknown. Primary insomnia can be caused by a traumatic event related to sleep or bedtime, and it is often
associated with increased physical or psychological
arousal at night. People who experience primary
insomnia are often anxious about not being able to
sleep. The person may then associate all sleep-related
things (their bed, bedtime, etc.) with frustration,
making the problem worse. The person then becomes
more stressed about not sleeping. Primary insomnia
usually begins when the person is a young adult or in
middle age.



Stage 1 NREM sleep. This stage occurs while a person is falling asleep. It represents about 5% of a
normal adult’s sleep time.



Stage 2 NREM sleep. In this stage, (the beginning of
‘‘true’’ sleep), the person’s electroencephalogram
(EEG) will show distinctive wave forms called sleep
spindles and K complexes. About 50% of sleep time
is stage 2 REM sleep.



Stages 3 and 4 NREM sleep. Also called delta or slow
wave sleep, these are the deepest levels of human
sleep and represent 10–20% of sleep time. They
usually occur during the first 30–50% of the sleeping
period.



REM sleep. REM sleep accounts for 20-25% of total
sleep time. It usually begins about 90 minutes after
the person falls asleep, an important measure called
REM latency. It alternates with NREM sleep about
every hour and a half throughout the night. REM
periods increase in length over the course of the
night.

Sleep cycles vary with a person’s age. Children
and adolescents have longer periods of stage 3 and
stage 4 NREM sleep than do middle aged or elderly
adults. Because of this difference, the doctor will need
to take a patient’s age into account when evaluating
a sleep disorder. Total REM sleep also declines
with age.
The average length of nighttime sleep varies
among people. Most people sleep between seven and
nine hours a night. This population average appears to
be constant throughout the world. In temperate
climates, however, people often notice that sleep time
varies with the seasons. It is not unusual for people in
North America and Europe to sleep about 40 minutes
longer per night during the winter.

Description
Sleep disorders are classified based on what causes
them. Primary sleep disorders are distinguished from
those that are not caused by other mental disorders,
3446

Dyssomnias

Hypersomnia is a condition marked by excessive
sleepiness during normal waking hours. The patient
has either lengthy episodes of daytime sleep or episodes of daytime sleep on a daily basis even though he
or she is sleeping normally at night. In some cases,
patients with primary hypersomnia have difficulty
waking in the morning and may appear confused or
angry. This condition is sometimes called sleep drunkenness and is more common in males. The number of
people with primary hypersomnia is unknown,
although 5–10% of patients in sleep disorder clinics
have the disorder. Primary hypersomnia usually
affects young adults between the ages of 15 and 30.
Nocturnal myoclonus and restless legs syndrome
(RLS) can cause either insomnia or hypersomnia in
adults. Patients with nocturnal myoclonus wake up
because of cramps or twitches in the calves. These
patients feel sleepy the next day. Nocturnal myoclonus
is sometimes called periodic limb movement disorder
(PLMD). RLS patients have a crawly or aching feeling
in their calves that can be relieved by moving or rubbing the legs. RLS often prevents the patient from
falling asleep until the early hours of the morning,
when the condition is less intense.
Kleine-Levin syndrome is a recurrent form of
hypersomnia that affects a person three or four times
a year. Doctors do not know the cause of this
GALE ENCYCLOPEDIA OF MEDICINE

Narcolepsy is a dyssomnia characterized by recurrent ‘‘sleep attacks’’ that the patient cannot fight. The
sleep attacks are about 10–20 minutes long. The
patient feels refreshed by the sleep, but typically feels
sleepy again several hours later. Narcolepsy has three
major symptoms in addition to sleep attacks: cataplexy, hallucinations, and sleep paralysis. Cataplexy is
the sudden loss of muscle tone and stability (‘‘drop
attacks’’). Hallucinations may occur just before falling
asleep (hypnagogic) or right after waking up (hypnopompic) and are associated with an episode of REM
sleep. Sleep paralysis occurs during the transition from
being asleep to waking up. About 40% of patients with
narcolepsy have or have had another mental disorder.
Although narcolepsy is often regarded as an adult
disorder, it has been reported in children as young as
three years old. Almost 18% of patients with narcolepsy are 10 years old or younger. It is estimated that
0.02–0.16% of the general population suffer from
narcolepsy. Men and women are equally affected.
Breathing-related sleep disorders are syndromes
in which the patient’s sleep is interrupted by problems
with his or her breathing. There are three types of
breathing-related sleep disorders:


Obstructive sleep apnea syndrome. This is the most
common form of breathing-related sleep disorder,
marked by episodes of blockage in the upper airway
during sleep. It is found primarily in obese people.
Patients with this disorder typically alternate between
periods of snoring or gasping (when their airway is
partly open) and periods of silence (when their airway
is blocked). Very loud snoring is a clue to this disorder.



Central sleep apnea syndrome. This disorder is primarily found in elderly patients with heart or neurological conditions that affect their ability to breathe
properly. It is not associated with airway blockage
and may be related to brain disease.



Central alveolar hypoventilation syndrome. This disorder is found most often in extremely obese people.
The patient’s airway is not blocked, but his or her
blood oxygen level is too low.



Mixed-type sleep apnea syndrome. This disorder
combines symptoms of both obstructive and central
sleep apnea.

Circadian rhythm sleep disorders are dyssomnias
resulting from a discrepancy between the person’s
GALE ENCYCLOPEDIA OF MEDICINE

daily sleep/wake patterns and demands of social
activities, shift work, or travel. The term circadian
comes from a Latin word meaning daily. There are
three circadian rhythm sleep disorders. Delayed sleep
phase type is characterized by going to bed and
arising later than most people. Jet lag type is caused
by travel to a new time zone. Shift work type is caused
by the schedule of a person’s job. People who are
ordinarily early risers appear to be more vulnerable
to jet lag and shift work-related circadian rhythm
disorders than people who are ‘‘night owls.’’ There
are some patients who do not fit the pattern of these
three disorders and appear to be the opposite of the
delayed sleep phase type. These patients have an
advanced sleep phase pattern and cannot stay
awake in the evening, but wake up on their own in
the early morning.
PARASOMNIAS. Parasomnias are primary sleep
disorders in which the patient’s behavior is affected
by specific sleep stages or transitions between sleeping
and waking. They are sometimes described as disorders of physiological arousal during sleep.

Nightmare disorder is a parasomnia in which the
patient is repeatedly awakened from sleep by frightening dreams and is fully alert on awakening. The actual
rate of occurrence of nightmare disorder is unknown.
Approximately 10–50% of children between three and
five years old have nightmares. They occur during
REM sleep, usually in the second half of the night.
The child is usually able to remember the content of
the nightmare and may be afraid to go back to sleep.
More females than males have this disorder, but it is
not known whether the sex difference reflects a difference in occurrence or a difference in reporting.
Nightmare disorder is most likely to occur in children
or adults under severe or traumatic stress.
Sleep terror disorder is a parasomnia in which the
patient awakens screaming or crying. The patient also
has physical signs of arousal, like sweating, shaking,
etc. It is sometimes referred to as pavor nocturnus.
Unlike nightmares, sleep terrors typically occur in
stage 3 or stage 4 NREM sleep during the first third
of the night. The patient may be confused or disoriented for several minutes and cannot recall the content of the dream. He or she may fall asleep again and
not remember the episode the next morning. Sleep
terror disorder is most common in children four to
12 years old and is outgrown in adolescence. It affects
about 3% of children. Fewer than 1% of adults have
the disorder. In adults, it usually begins between the
ages of 20 and 30. In children, more males than
females have the disorder. In adults, men and women
are equally affected.
3447

Sleep disorders

syndrome. It is marked by two to three days of sleeping 18–20 hours per day, hypersexual behavior, compulsive eating, and irritability. Men are three times
more likely than women to have the syndrome.
Currently, there is no cure for this disorder.

Sleep disorders

Sleepwalking disorder, which is sometimes called
somnambulism, occurs when the patient is capable of
complex movements during sleep, including walking.
Like sleep terror disorder, sleepwalking occurs during
stage 3 and stage 4 NREM sleep during the first part
of the night. If the patient is awakened during a
sleepwalking episode, he or she may be disoriented
and have no memory of the behavior. In addition to
walking around, patients with sleepwalking disorder
have been reported to eat, use the bathroom, unlock
doors, or talk to others. It is estimated that 10–30% of
children have at least one episode of sleepwalking.
However, only 1–5% meet the criteria for sleepwalking disorder. The disorder is most common in
children eight to 12 years old. It is unusual for sleepwalking to occur for the first time in adults.
Unlike sleepwalking, REM sleep behavior disorder occurs later in the night and the patient can
remember what they were dreaming. The physical
activities of the patient are often violent.
Sleep disorders related to other conditions
In addition to the primary sleep disorders, there
are three categories of sleep disorders that are caused
by or related to substance use or other physical or
mental disorders.
SLEEP
DISORDERS
RELATED
TO
MENTAL
DISORDERS. Many mental disorders, especially

depression or one of the anxiety disorders, can cause
sleep disturbances. Psychiatric disorders are the most
common cause of chronic insomnia.
SLEEP
DISORDERS
DUE
TO
MEDICAL
CONDITIONS. Some patients with chronic neurological

conditions like Parkinson’s disease or Huntington’s
disease may develop sleep disorders. Sleep disorders
have also been associated with viral encephalitis, brain
disease, and hypo- or hyperthyroidism.
SUBSTANCE-INDUCED SLEEP DISORDERS. The use
of drugs, alcohol, and caffeine frequently produces
disturbances in sleep patterns. Alcohol abuse is associated with insomnia. The person may initially feel
sleepy after drinking, but wakes up or sleeps fitfully
during the second half of the night. Alcohol can also
increase the severity of breathing-related sleep disorders. With amphetamines or cocaine, the patient typically suffers from insomnia during drug use and
hypersomnia during drug withdrawal. Opioids usually
make short-term users sleepy. However, long-term
users develop tolerance and may suffer from insomnia.

In addition to alcohol and drugs that are abused, a
variety of prescription medications can affect sleep
patterns. These medications include antihistamines,
3448

corticosteroids, asthma medicines, and drugs that
affect the central nervous system.
Sleep disorders in children and adolescents
Pediatricians estimate that 20–30% of children
have difficulties with sleep that are serious enough to
disturb their families. Although sleepwalking and
night terror disorder occur more frequently in children
than in adults, children can also suffer from narcolepsy and sleep apnea syndrome.

Causes and symptoms
The causes of sleep disorders have already been
discussed with respect to the classification of these
disorders.
The most important symptoms of sleep disorders
are insomnia and sleepiness during waking hours.
Insomnia is by far the more common of the two symptoms. It covers a number of different patterns of sleep
disturbance. These patterns include inability to fall
asleep at bedtime, repeated awakening during the
night, and/or inability to go back to sleep once
awakened.

Diagnosis
Diagnosis of sleep disorders usually requires a
psychological history as well as a medical history.
With the exception of sleep apnea syndromes, physical
examinations are not usually revealing. The patient’s
sex and age are useful starting points in assessing the
problem. The doctor may also talk to other family
members in order to obtain information about the
patient’s symptoms. The family’s observations are
particularly important to evaluate sleepwalking, kicking in bed, snoring loudly, or other behaviors that the
patient cannot remember.
Sleep logs
Many doctors ask patients to keep a sleep diary or
sleep log for a minimum of one to two weeks in order
to evaluate the severity and characteristics of the sleep
disturbance. The patient records medications taken as
well as the length of time spent in bed, the quality of
the sleep, and similar information. Some sleep logs are
designed to indicate circadian sleep patterns as well as
simple duration or restfulness of sleep.
Psychological testing
The doctor may use psychological tests or inventories to evaluate insomnia because it is frequently
GALE ENCYCLOPEDIA OF MEDICINE

Sleep disorders
A patient suffering from acute sleep apnea is hooked up to monitors in preparation for a night’s sleep at a Stanford University
sleep lab. (Photograph by Russell D. Curtis, Photo Researchers, Inc. Reproduced by permission.)

associated with mood or affective disorders. The
Minnesota
Multiphasic
Personality
Inventory
(MMPI), the Millon Clinical Multiaxial Inventory
(MCMI), the Beck Depression Inventory, and the
Zung Depression Scale are the tests most commonly
used in evaluating this symptom.
SELF-REPORT TESTS. The Epworth Sleepiness Scale,

a self-rating form recently developed in Australia,
consists of eight questions used to assess daytime sleepiness. Scores range from 0–24, with scores higher
than 16 indicating severe daytime sleepiness.
Laboratory studies
If the doctor is considering breathing-related
sleep disorders, myoclonus, or narcolepsy as possible
diagnoses, he or she may ask the patient to be tested
in a sleep laboratory or at home with portable
instruments.
POLYSOMNOGRAPHY. Polysomnography can be
used to help diagnose sleep disorders as well as conduct research into sleep. In some cases the patient is

GALE ENCYCLOPEDIA OF MEDICINE

tested in a special sleep laboratory. The advantage of
this testing is the availability and expertise of trained
technologists, but it is expensive. As of 2001, however,
portable equipment is available for home recording of
certain specific physiological functions.
MULTIPLE SLEEP LATENCY TEST (MSLT). The multiple
sleep latency test (MSLT) is frequently used to measure the severity of the patient’s daytime sleepiness.
The test measures sleep latency (the speed with which
the patient falls asleep) during a series of planned naps
during the day. The test also measures the amount of
REM sleep that occurs. Two or more episodes of
REM sleep under these conditions indicates narcolepsy. This test can also be used to help diagnose
primary hypersomnia.
REPEATED TEST OF SUSTAINED WAKEFULNESS
(RTSW). The repeated test of sustained wakefulness

(RTSW) is a test that measures sleep latency by challenging the patient’s ability to stay awake. In the RTSW,
the patient is placed in a quiet room with dim lighting
and is asked to stay awake. As with the MSLT, the
testing pattern is repeated at intervals during the day.
3449

Sleep disorders

Treatment
Treatment for a sleep disorder depends on what
is causing the disorder. For example, if major depression is the cause of insomnia, then treatment of the
depression with antidepressants should resolve the
insomnia.
Medications
Sedative or hypnotic medications are generally
recommended only for insomnia related to a temporary stress (like surgery or grief) because of the potential for addiction or overdose. Trazodone, a sedating
antidepressant, is often used for chronic insomnia that
does not respond to other treatments. Sleep medications may also cause problems for elderly patients
because of possible interactions with their other prescription medications. Among the safer hypnotic
agents are lorazepam, temazepam, and zolpidem.
Chloral hydrate is often preferred for short-term treatment in elderly patients because of its mildness. Shortterm treatment is recommended because this drug may
be habit forming.
Narcolepsy is treated with stimulants such as dextroamphetamine
sulfate
or
methylphenidate.
Nocturnal myoclonus has been successfully treated
with clonazepam.
Children with sleep terror disorder or sleepwalking are usually treated with benzodiazepines because
this type of medication suppresses stage 3 and stage 4
NREM sleep.
Psychotherapy
Psychotherapy is recommended for patients with
sleep disorders associated with other mental disorders.
In many cases the patient’s scores on the Beck or Zung
inventories will suggest the appropriate direction of
treatment.
Sleep education
‘‘Sleep hygiene’’ or sleep education for sleep disorders often includes instructing the patient in methods to enhance sleep. Patients are advised to:


wait until he or she is sleepy before going to bed



avoid using the bedroom for work, reading, or
watching television



get up at the same time every morning no matter how
much or how little he or she slept



avoid smoking and avoid drinking liquids with
caffeine

3450



get some physical exercise early in the day every day



limit fluid intake after dinner; in particular, avoid
alcohol because it frequently causes interrupted sleep



learn to meditate or practice relaxation techniques



avoid tossing and turning in bed; instead, he or she
should get up and listen to relaxing music or read
Lifestyle changes

Patients with sleep apnea or hypopnea are encouraged to stop smoking, avoid alcohol or drugs of abuse,
and lose weight in order to improve the stability of the
upper airway.
In some cases, patients with sleep disorders related
to jet lag or shift work may need to change employment or travel patterns. Patients may need to avoid
rapid changes in shifts at work.
Children with nightmare disorder may benefit
from limits on television or movies. Violent scenes or
frightening science fiction stories appear to influence
the frequency and intensity of children’s nightmares.
Surgery
Although making a surgical opening into the
windpipe (a tracheostomy) for sleep apnea or hypopnea in adults is a treatment of last resort, it is occasionally performed if the patient’s disorder is life
threatening and cannot be treated by other methods.
In children and adolescents, surgical removal of the
tonsils and adenoids is a fairly common and successful
treatment for sleep apnea. Most sleep apnea patients
are treated with continuous positive airway pressure
(CPAP). Sometimes an oral prosthesis is used for mild
sleep apnea.

Alternative treatment
Some alternative approaches may be effective in
treating insomnia caused by anxiety or emotional
stress. Meditation practice, breathing exercises, and
yoga can break the vicious cycle of sleeplessness,
worry about inability to sleep, and further sleeplessness for some people. Yoga can help some people to
relax muscular tension in a direct fashion. The breathing exercises and meditation can keep some patients
from obsessing about sleep.
Homeopathic practitioners recommend that
people with chronic insomnia see a professional
homeopath. They do, however, prescribe specific
remedies for at-home treatment of temporary insomnia: Nux vomica for alcohol or substancerelated insomnia, Ignatia for insomnia caused by
GALE ENCYCLOPEDIA OF MEDICINE

Apnea—The temporary absence of breathing. Sleep
apnea consists of repeated episodes of temporary
suspension of breathing during sleep.
Cataplexy—Sudden loss of muscle tone (often causing a person to fall), usually triggered by intense emotion. It is regarded as a diagnostic sign of narcolepsy.
Circadian rhythm—Any body rhythm that recurs in
24-hour cycles. The sleep-wake cycle is an example
of a circadian rhythm.
Dyssomnia—A primary sleep disorder in which the
patient suffers from changes in the quantity, quality,
or timing of sleep.
Electroencephalogram (EEG)—The record obtained
by a device that measures electrical impulses in the
brain.
Hypersomnia—An abnormal increase of 25% or
more in time spent sleeping. Patients usually have
excessive daytime sleepiness.
Hypnotic—A medication that makes a person sleep.
Hypopnea—Shallow or excessively slow breathing
usually caused by partial closure of the upper airway
during sleep, leading to disruption of sleep.
Insomnia—Difficulty in falling asleep or remaining
asleep.
Jet lag—A temporary disruption of the body’s sleepwake rhythm following high-speed air travel across
several time zones. Jet lag is most severe in people
who have crossed eight or more time zones in 24 hours.
Kleine-Levin syndrome—A disorder that occurs primarily in young males, three or four times a year. The
syndrome is marked by episodes of hypersomnia,
hypersexual behavior, and excessive eating.
Narcolepsy—A life-long sleep disorder marked by
four symptoms: sudden brief sleep attacks, cataplexy, temporary paralysis, and hallucinations. The
hallucinations are associated with falling asleep or
the transition from sleeping to waking.
Nocturnal myoclonus—A disorder in which the
patient is awakened repeatedly during the night by

grief, Arsenicum for insomnia caused by fear or anxiety, and Passiflora for insomnia related to mental
stress.
Melatonin has also been used as an alternative
treatment for sleep disorders. Melatonin is produced
in the body by the pineal gland at the base of the brain.
GALE ENCYCLOPEDIA OF MEDICINE

cramps or twitches in the calf muscles. Nocturnal
myoclonus is sometimes called periodic limb movement disorder (PLMD).
Non-rapid eye movement (NREM) sleep—A type of
sleep that differs from rapid eye movement (REM)
sleep. The four stages of NREM sleep account for
75–80% of total sleeping time.
Parasomnia—A primary sleep disorder in which the
person’s physiology or behaviors are affected by
sleep, the sleep stage, or the transition from sleeping
to waking.
Pavor nocturnus—Another term for sleep terror
disorder.
Polysomnography—Laboratory measurement of a
patient’s basic physiological processes during
sleep. Polysomnography usually measures eye
movement, brain waves, and muscular tension.
Primary sleep disorder—A sleep disorder that cannot be attributed to a medical condition, another
mental disorder, or prescription medications or
other substances.
Rapid eye movement (REM) sleep—A phase of sleep
during which the person’s eyes move rapidly
beneath the lids. It accounts for 20–25% of sleep
time. Dreaming occurs during REM sleep.
REM latency—After a person falls asleep, the
amount of time it takes for the first onset of REM
sleep.
Restless legs syndrome (RLS)—A disorder in which
the patient experiences crawling, aching, or other
disagreeable sensations in the calves that can be
relieved by movement. RLS is a frequent cause of
difficulty falling asleep at night.
Sedative—A medication given to calm agitated
patients; sometimes used as a synonym for hypnotic.
Sleep latency—The amount of time that it takes to
fall asleep. Sleep latency is measured in minutes and
is important in diagnosing depression.
Somnambulism—Another term for sleepwalking.

This substance is thought to be related to the body’s
circadian rhythms.
Practitioners of Chinese medicine usually treat
insomnia as a symptom of excess yang energy. Cinnabar
is recommended for chronic nightmares. Either magnetic magnetite or ‘‘dragon bones’’ is recommended
3451

Sleep disorders

KEY TERMS

Sleeping sickness

for insomnia associated with hysteria or fear. If the
insomnia appears to be associated with excess yang
energy arising from the liver, the practitioner will give
the patient oyster shells. Acupuncture treatments can
help bring about balance and facilitate sleep.
Dietary changes like eliminating stimulant foods
(coffee, cola, chocolate) and late-night meals or snacks
can be effective in treating some sleep disorders.
Nutritional supplementation with magnesium, as well
as botanical medicines that calm the nervous system,
can also be helpful. Among the botanical remedies
that may be effective for sleep disorders are valerian
(Valeriana officinalis), passionflower (Passiflora incarnata ), and skullcap (Scutellaria lateriflora).

Prognosis
The prognosis depends on the specific disorder.
Children usually outgrow sleep disorders. Patients
with Kleine-Levin syndrome usually get better around
age 40. Narcolepsy is a life-long disorder. The prognosis
for sleep disorders related to other conditions depends
on successful treatment of the substance abuse, medical
condition, or other mental disorder. The prognosis for
primary sleep disorders is affected by many things,
including the patient’s age, sex, occupation, personality
characteristics, family circumstances, neighborhood
environment, and similar factors.
Resources
BOOKS

Moe, Paul G., and Alan R. Seay. ‘‘Neurologic & Muscular
Disorders: Sleep Disorders.’’ In Current Pediatric
Diagnosis & Treatment, edited by William W. Hay Jr.,
et al. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Sleep study see Polysomnography
Sleeping drugs see Anti-insomnia drugs

Sleeping sickness
Definition
Sleeping sickness (also called trypanosomiasis) is
an infection caused by Trypanosoma protozoa; it is
passed to humans through the bite of the tsetse fly. If
left untreated, the infection progresses to death within
months or years.
3452

D A V I D B R U C E (1855–1931)
David Bruce was born in Melbourne, Australia, on
May 29,1855, to Scottish immigrants. Bruce’s family
moved back to Scotland when he was five years old.
Bruce attended the University of Edinburgh where he
studied natural history and medicine. Following his graduation, he accepted a position working with a doctor. In
1883, Bruce married Mary Elizabeth Steele who would
help him with his work throughout his life.
In 1884, Bruce began to study the disease ‘‘Malta,
Mediterranean’’ when he and Mary were stationed in
Malta with the Army Medical Service. Using a microscope, Bruce discovered that the disease was caused by
a ‘‘microccus’’ that grew in the individual’s spleen. The
organism responsible for this disease was ultimately
isolated by Bernhard L. F. Bang. In 1905, Bruce led a
scientific team that discovered that the soldiers who
contracted the disease had ingested the milk of infected
goats. The disease disappeared when the soldiers quit
drinking goat’s milk. Many physicians began calling the
disease ‘‘brucellosis’’ in honor of Bruce’s discoveries.
Bruce also conducted research in Africa where he found
that the tsetse fly could infect humans, as well as animals,
with the ‘‘nagana’’ disease. Ultimately, his work would
prove that sleeping sickness was caused by the tsetse fly.
In 1903, Bruce became the director of the Royal
Society’s Sleeping Sickness Commission and, in 1908,
he was knighted. He served as commandant of the Royal
Army Medical College after he and his wife returned to
England. Bruce died on November 20, 1931.

Description
Protozoa are single-celled organisms considered
to be the simplest life form in the animal kingdom.
The protozoa responsible for sleeping sickness are a
variety that bear numerous flagella (hair-like projections from the cell that help the cell to move). These
protozoa exist only on the continent of Africa. The
type of protozoa causing sleeping sickness in humans
is referred to as the Trypanasoma brucei complex,
which can be divided further into Rhodesian
(Central and East African) and Gambian (Central
and West African) subspecies.
The Rhodesian variety live within antelopes in
savanna and woodland areas, and they cause no problems with the antelope’s health. The protozoa are
then acquired by tsetse flies when they bite and suck
the blood of an infected antelope or cow.
Within the tsetse fly, the protozoa cycle through
several different life forms; ultimately they migrate to
GALE ENCYCLOPEDIA OF MEDICINE

Humans most likely to become infected by
Rhodesian trypanosomes are people such as game
wardens and visitors to game parks in East Africa,
who may be bitten by a tsetse fly that has fed on game
(antelope) carrying the protozoa. The Rhodesian variety of sleeping sickness causes a much more severe
illness, with even greater likelihood of eventual death
than the Gambian form.
The Gambian variety of Trypanosoma thrives in
tropical rain forests throughout Central and West
Africa; it does not infect game or cattle, and is primarily a threat to people dwelling in such areas, rarely
infecting visitors.

Causes and symptoms
The first sign of infection with the trypanosome
may be a sore appearing at the site of the tsetse fly bite
about two to tree days after having been bitten.
Redness, pain, and swelling occur, but are often
ignored by the patient.
Stage I illness
Two to three weeks later, Stage I disease develops
as a result of the protozoa being carried through the
blood and lymph circulation of the host. This systemic
(meaning that symptoms affect the whole body) phase
of the illness is characterized by a fever that rises quite
high, then falls to normal, then respikes (rises rapidly).
A rash with intense itching may be present, and headache and mental confusion may occur. The Gambian
form, in particular, includes extreme swelling of lymph
tissue, with enlargement of both the spleen and liver,
and greatly swollen lymph nodes. ‘‘Winterbottom’s
sign’’ is classic of Gambian sleeping sickness, and
consists of a visibly swollen area of lymph nodes
located behind the ear and just above the base of the
neck. During this stage, the heart may be affected by a
severe inflammatory reaction, particularly when the
infection is caused by the Rhodesian variety of
trypanosomiasis.
Many of the symptoms of sleeping sickness are
actually the result of attempts by the patient’s immune
system to get rid of the invading organism. The heightened activity of the cells of the immune system result
in damage to the patient’s own organs, anemia, and
leaky blood vessels. These leaks in the blood vessels
end up helping to further spread the protozoa
throughout the afflicted person’s body.
GALE ENCYCLOPEDIA OF MEDICINE

One reason for the intense reaction of the
immune system to the presence of the trypanosomes
is also the reason why the trypanosomes survive so
well despite the efforts of the immune system to eradicate them. The protozoa causing sleeping sickness
are able to rapidly change specific markers (unique
proteins) on their outer coats. These kinds of markers
usually serve to stimulate the host’s immune system
to produce immune cells that will specifically target
the marker, allowing quick destruction of those cells
bearing the markers. Trypanosomes, however, are
able to express new markers at such a high rate of
change that the host’s immune system is constantly
trying to catch up.
Stage II illness
Stage II sleeping sickness involves the nervous
system. Gambian sleeping sickness, in particular, has
a clearly delineated phase in which the predominant
symptoms involve the brain. The patient’s speech
becomes slurred, mental processes slow, and the
patient sits and stares for long periods of time, or
sleeps. Other symptoms resemble Parkinson’s disease,
including imbalance when walking, slow and shuffling
gait, trembling of the limbs, involuntary movements,
muscle tightness, and increasing mental confusion.
Untreated, these symptoms eventually lead to coma
and then to death.

Diagnosis
Diagnosis of sleeping sickness can be made by
microscopic examination of fluid from the original
sore at the site of the tsetse fly bite. Trypanosomes
will be present in the fluid for a short period of time
following the bite. If the sore has already resolved,
fluid can be obtained from swollen lymph nodes for
examination. Other methods of trypanosome diagnosis involve culturing blood, lymph node fluid, bone
marrow, or spinal fluid. These cultures are then
injected into rats, which develop blood-borne protozoa infection that can be detected in blood smears
within one to two weeks. However, this last method
is effective only for the Rhodesian variety of sleeping
sickness.

Treatment
Without treatment, sleeping sickness will lead to
death. Unfortunately, however, those medications
effective against the Trypanosoma brucei complex
protozoa all have significant potential side effects for
the patient. Suramin, eflornithine, pentamidine, and
3453

Sleeping sickness

the salivary glands of the tsetse fly. Once the protozoa
are harbored in the salivary glands, they are ready to
be deposited into the bloodstream of the fly’s next
source of a blood meal.

Small intestine biopsy

KEY TERMS
Immune system—That network of tissues and cells
throughout the body that is responsible for ridding
the body of any invaders, such as viruses, bacteria,
protozoa, etc.
Protozoa—Single-celled organisms considered to
be the simplest life form in the animal kingdom.

several drugs that contain arsenic (a chemical which in
higher doses is highly poisonous to humans), are all
effective anti-trypanosomal agents. Each of these
drugs, however, requires careful monitoring to ensure
that the drugs themselves do not cause serious complications such as fatal hypersensitivity (allergic) reaction, kidney or liver damage, or inflammation of the
brain.

Small intestine biopsy
Definition
A biopsy is a diagnostic procedure in which tissue
or cells are removed from a part of the body and
specially prepared for examination under a microscope. When the tissue involved is part of the small
intestine, the procedure is called a small-intestine (or
small-bowel) biopsy.

Purpose
The small-bowel biopsy is used to diagnose and
confirm disease of the intestinal mucosa (the lining of
the small intestine). The test is most commonly done to
test for tumors of the small bowel or malabsorption
syndromes.

Precautions
Prevention
Prevention of sleeping sickness requires avoiding
contact with the tsetse fly. Insect repellents and clothing that covers the limbs to the wrists and ankles are
advisable. Public health measures have included drug
treatment of humans who are infected with one of the
Trypanosoma brucei complex. There are currently no
immunizations available to prevent the acquisition of
sleeping sickness.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Sleepwalking see Sleep disorders
Slipped disk see Herniated disk
Slit lamp examination see Eye examination
Small-for-gestational-age infant see
Intrauterine growth retardation
Small bowel follow-through (SBFT) see
Upper GI exam
Small cell lung cancer see Lung cancer, small
cell
3454

Due to the slight risk of bleeding during or after
this procedure, aspirin, aspirin-containing medications, nonsteroidal anti-inflammatory drugs, and anticoagulants and antiplatelet drugs should be withheld
for at least five days before the test.

Description
The small intestine is approximately 21 ft (6.4m).
It has three sections: the duodenum (a short, curved
segment fixed to the back wall of the abdomen), the
jejunum, and the ileum (two larger, coiled, and mobile
segments). Some digestion occurs in the stomach, but
the small intestine is mainly responsible for digestion
and absorption of foods.
Malabsorption syndromes occur when certain
conditions result in impaired absorption of nutrients,
vitamins, or minerals from the diet by the lining of the
small intestine. For example, injury to the intestinal
lining can interfere with absorption, as can infections,
intestinal parasites, some drugs, blockage of the lymphatic vessels, poor blood supply to the intestine, or
diseases like sprue.
Malabsorption is suspected when a patient not
only loses weight, but has diarrhea and nutritional
deficiencies despite eating well (weight loss alone
can have other causes). Laboratory tests like fecal
fat, a measurement of fat in stool samples collected
over 72 hours, are the most reliable tests for diagnosing fat malabsorption, but abnormalities of the small
intestine itself are diagnosed by small-intestine
biopsy.
GALE ENCYCLOPEDIA OF MEDICINE

Several similar types of capsules are used for tissue
collection. In each, a mercury-weighted bag is
attached to one end of the capsule, while a thin polyethylene tube about 5 ft (1.5m) long is attached to the
other end. Once the bag, capsule, and tube are in place
in the small bowel, suction on the tube draws the tissue
into the capsule and closes it, cutting off the piece of
tissue within. This is an invasive procedure, but it
causes little pain and complications are rare.
A newer method of obtaining diagnostic information about the small intestine was approved by the Food
and Drug Administration (FDA) in 2001. Known as the
M2A Imaging System, the device was developed by a
company in Atlanta, Georgia. The M2A system consists of an imaging capsule, a portable belt-pack image
receiver and recorder, and a specially modified computer. The patient swallows the capsule, which is the size of
a large pill. A miniature lens in the capsule transmits
images through an antenna/transmitter to the belt-pack
receiver, which the patient wears under ordinary
clothing as he or she goes about daily activities. The
belt-pack recording device is returned after seven or
eight hours to the doctor, who then examines the images
recorded as a digital video. The capsule itself is simply
allowed to pass through the digestive tract.
Preparation requires only fasting the night before
the M2A examination and taking nothing but clear
liquids for two hours after swallowing the capsule.
After four hours the patient can eat food without interfering with the test. As of the early 2000s, the M2A
system is used to evaluate gastrointestinal bleeding
from unknown causes, inflammatory bowel disease,
some malabsorption syndromes, and to monitor
surgical patients following small-bowel transplantation. The system has shown good results in detecting
Crohn’s disease undiagnosed by conventional methods.
Small-intestine biopsy procedure
After application of a topical anesthetic to the back
of the patient’s throat, the capsule and the tube are
introduced, and the patient is asked to swallow as the
tube is advanced. The patient is then placed on the right
side and the instrument tip is advanced another 20 in
(51cm) or so. The tube’s position is checked by
GALE ENCYCLOPEDIA OF MEDICINE

fluoroscopy or by instilling air through the tube and
listening with a stethoscope for air to enter the stomach.
The tube is advanced 2–4 in (5.1–10 cm)at a time to
pass the capsule through the stomach outlet (pylorus).
When fluoroscopy confirms that the capsule has passed
the pylorus, small samples of small intestine tissue are
obtained by the instrument’s cutting edge, after which
the instrument and tube are withdrawn. The entire
procedure may be completed in minutes.

Preparation
This procedure requires tissue specimens from the
small intestine through means of a tube inserted into
the stomach through the mouth. The patient is to
withhold food and fluids for at least eight hours before
the test.

Aftercare
The patient should not have anything to eat or
drink until the topical anesthetic wears off (usually
about one to two hours). If intravenous sedatives were
administered during the procedure, the patient should
not drive for the remainder of the day. Complications
from this procedure are uncommon, but can occur. The
patient is to note any abdominal pain or bleeding and
report either immediately to the doctor.

Risks
Complications from this procedure are rare, but
can include bleeding (hemorrhage), bacterial infection
with fever and pain, and bowel puncture (perforation).
The patient should immediately report any abdominal
pain or bleeding to the physician in charge. Biopsy is
contraindicated in uncooperative patients, those taking aspirin or anticoagulants, and in those with uncontrolled bleeding disorders.

Normal results
Normal results are no abnormalities seen on gross
examination of the specimen(s) or under the microscope after tissue preparation.

Abnormal results
Small-intestine tissue exhibiting abnormalities
may indicate Whipple’s disease, a malabsorption disease; lymphoma, a group of cancers; and parasitic
infections like giardiasis, strongyloidiasis, and coccidiosis. When biopsy indicates celiac sprue (a malabsorption
disorder),
infectious
gastroenteritis
3455

Small intestine biopsy

Several different methods are used to detect
abnormalities of the small intestine. A tissue specimen
can be obtained by using an endoscope (a flexible viewing tube), or by using a thin tube with a small cutting
instrument at the end. This latter procedure is ordered
when specimens larger than those provided by endoscopic biopsy are needed, because it allows removal of
tissue from areas beyond the reach of an endoscope.

Smallpox

KEY TERMS
Sprue—A disorder of impaired absorption of nutrients from the diet by the small intestine (malabsorption), resulting in malnutrition. Two forms of sprue
exist: tropical sprue, which occurs mainly in tropical
regions; and celiac sprue, which occurs more widely
and is due to sensitivity to the wheat protein gluten.
Whipple’s disease—A disorder of impaired absorption of nutrients by the small intestine. Symptoms
include diarrhea, abdominal pain, progressive
weight loss, joint pain, swollen lymph nodes,
abnormal skin pigmentation, anemia, and fever.
The precise cause is unknown, but it is probably
due to an unidentified bacterial infection.
Wireless capsule endoscopy—A newer method of
examining the small bowel by means of a capsule
swallowed by the patient. The capsule contains a
miniaturized lens and an antenna that transmits
information to a belt-pack recorder worn by the
patient during the day.

(inflammation of the gastrointestinal tract), folate and
B12 deficiency, or malnutrition, confirmation studies
are needed for conclusive diagnosis.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Malabsorption Syndromes.’’ Section 3, Chapter 30 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Small-Bowel Tumors.’’ Section 3, Chapter 34 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Adler, Douglas J., MD, and Christopher J. Gostout, MD.
‘‘Wireless Capsule Endoscopy.’’ Hospital Physician
May 2003: 17–22.
Ge, Z. Z., Y. B. Hu, and S. D. Xiao. ‘‘Capsule Endoscopy in
Diagnosis of Small Bowel Crohn’s Disease.’’ World
Journal of Gastroenterology 10 (May 1, 2004): 1349–1352.
Thompson, B. F., L. C. Fry, C. D. Wells, et al. ‘‘The
Spectrum of GI Strongyloidiasis: An EndoscopicPathologic Study.’’ Gastrointestinal Endoscopy 59 (June
2004): 906–910.

Janis O. Flores
Rebecca J. Frey, PhD
3456

Smallpox
Definition
Smallpox is an infection caused by the variola
virus, a member of the poxvirus family. Throughout
history, smallpox has been a greatly feared disease
because it was responsible for huge epidemics worldwide that resulted in large numbers of deaths. In 1980,
the World Health Organization (WHO) announced
that an extensive program of vaccination against the
disease had resulted in the complete eradication of the
virus, with the exception of samples of stored virus in
two laboratories.

Description
Smallpox is strictly an infection of human beings.
Animals and insects can neither be infected by smallpox, nor carry the virus in any form. Most infections
are caused by contact with a person who has already
developed the characteristic skin lesions (pox) of the
disease, although a person who has a less severe infection (not symptomatic or diagnosable in the usual
way) can unwittingly spread the virus.

Causes and symptoms
Smallpox is a relatively contagious disease, which
accounts for its ability to cause massive epidemics. The
variola virus is acquired from direct contact with individuals infected with the disease, from contaminated
air droplets, and even from objects used by another
smallpox victim (books, blankets, utensils, etc.). The
respiratory tract is the usual entry point for the variola
virus into a human being.
After the virus enters the body, there is a 12–14
day incubation period during which the virus multiplies, although no symptoms are recognizable. After
the incubation period, symptoms appear abruptly and
include fever, chills, and muscle aches. Two to three
days later, a bumpy rash begins appearing first on the
face and forearms. The rash progresses, ultimately
reaching the chest, abdomen, and back. Seven to ten
days after the rash appears, the patient is most infectious. The individual bumps (papules) fill with clear
fluid and eventually become pus-filled over the course
of 10–12 days. These pox eventually scab over, each
leaving a permanently scarred pock or pit when the
scab drops off.
Initially, the smallpox symptoms and rash appear
similar to chickenpox. However, unlike chickenpox,
smallpox lesions develop at the same rate so that
GALE ENCYCLOPEDIA OF MEDICINE

Smallpox

they are all visible in the same stage. Another major
difference is that smallpox occurs primarily on the face
and entremities, whereas chickenpox tends to be concentrate on the face and trunk area.
Complications such as bacterial infection of the
open skin lesions, pneumonia, or bone infections are
the major causes of death from smallpox. A very severe
and quickly fatal form called ‘‘sledgehammer smallpox,’’ occurs in 5-10% of patients and results in massive, uncontrollable bleeding (hemorrhage) from the
skin lesions, as well as from the mouth, nose, and other
areas of the body. This form is very infectious and
usually fatal five to seven days after onset.
Fear of smallpox comes from both the epidemic
nature of the disease, as well as from the fact that no
therapies have ever been discovered to either treat the
symptoms of smallpox, or shorten the course of the
disease.

Diagnosis
In modern times, a diagnosis of smallpox is made
using an electron microscope to identify virus in fluid
from the papules, urine, or in the patient’s blood prior
to the appearance of the papular rash.

Treatment
No treatments have been developed to halt the
progression of the disease. Treatment for smallpox is
only supportive, meaning that it is aimed at keeping a
patient as comfortable as possible. Antibiotics are
sometimes administered to prevent secondary bacterial infections.

Prognosis
Approximately one in three patients die from
smallpox, with the more severe, hemorrhagic form
nearly 100% fatal. Patients who survive smallpox
infection nearly always have multiple areas of scarring
where each pock has been.

Prevention
From about the tenth century in China, India, and
the Americas, it is noted that individuals who had even
a mild case of smallpox could not be infected again.
Fascinating accounts appear in writings from all over
the world of ways in which people tried to prevent
smallpox. Material from people mildly ill with smallpox (fluid or pus from the papules, scabs over the pox)
was scratched into the skin of people who had never
had the illness, in an attempt to produce a mild
GALE ENCYCLOPEDIA OF MEDICINE

Smallpox pustules on the arm of an Asian Indian man.
(Photograph by C. James Webb, Phototake NYC. Reproduced
by permission.)

reaction and its accompanying protective effect.
These efforts often resulted in full-fledged smallpox,
and probably served only to help effectively spread the
infection throughout a community. In fact, such crude
smallpox ‘‘vaccinations’’ were against the law in
Colonial America.
In 1798, Edward Jenner published a paper in
which he discussed his important observation that
milkmaids who contracted a mild infection of the
hands (called cowpox, and caused by a relative of
the variola virus) appeared to be immune to smallpox. Jenner created an immunization against smallpox using the pus found in the lesions of cowpox
infection. Jenner’s paper led to much work in the
area of vaccinations, and ultimately resulted in the
creation of a very effective vaccination against smallpox that utilized the vaccinia virus, another close
relative of variola. Indeed, the term vaccination is
derived from vacce, Latin for cow and related to the
3457

Smallpox

cowpox link. Later, the term was applied to other
vaccinations.
In 1967, WHO began its attempt to eradicate the
smallpox virus worldwide. The methods used in the
program were simple:


Careful surveillance for all smallpox infections
worldwide, to allow for quick diagnosis and immediate quarantine of patients.



Immediate vaccination of all contacts diagnosed
with infection, in order to interrupt the virus’ usual
pattern of infection.

The WHO’s program was extremely successful,
and the virus was declared eradicated worldwide in
May 1980.

Future concerns
Today, two laboratories (the Centers for Disease
Control and Prevention in Atlanta, Georgia, and the
Russian State Centre for Research on Virology and
Biotechnology in Koltsovo, Novosibirsk Region)
officially retain samples of the smallpox virus. These
samples, as well as stockpiles of the smallpox vaccine,
are stored because some level of concern exists that
another poxvirus could undergo genetic changes
(mutate) and cause human infection. There is also
the remote chance that smallpox virus could somehow
escape from the laboratories where it is stored. For
these reasons, surveillance continues of various animal
groups that continue to be infected with viruses related
to the variola virus, and large quantities of vaccine are
stored in different countries around the world, so that
response to any future threat by the smallpox virus
could be prompt.
Of greatest concern is the potential use of smallpox as a biological weapon. Since 1980, when the
WHO announced smallpox had been eradicated,
essentially no one has been vaccinated against the
disease. Those individuals vaccinated prior to 1980
are believed to be susceptible as well because immunity
only lasts 15-20 years. These circumstances coupled
with the nature of smallpox to spread quickly from
person to person could lead to devastating
consequences.
The United States and Russia are the only two
countries to officially house remaining samples of the
virus. However, it is believed that other countries, such
as Iraq, may have obtained samples of the smallpox
virus during the Cold War through their association
with Russia. It is also possible that scientists with
access to the virus may have sold their services and
knowledge to other governments.
3458

KEY TERMS
Epidemic—A situation in which a particular infection is experienced by a very large percentage of the
people in a given community within a given time
frame.
Eradicate—To completely do away with something, eliminate it, end its existence.
Hemorrhage—Bleeding that is massive, uncontrollable, and often life-threatening.
Lesion—The tissue disruption or the loss of function
caused by a particular disease process.
Papules—Firm bumps on the skin.
Pox—A pus-filled bump on the skin.
Vaccine—A preparation using a non-infectious element or relative of a particular virus or bacteria, and
administered with the intention of halting the progress of an infection, or completely preventing it.

On June 22-23, 2001, four U.S. organizations
(CSIS—Center for Strategic and International
Studies, Johns Hopkins Center for Civilian
Biodefense Studies, ANSER—Analytic Services Inc.,
and MIPT—Memorial Institute for the Prevention of
Terrorism) presented a fictitious scenario of the
United States’ response to a deliberate introduction
of smallpox titled Dark Winter. This exercise demonstrated that if such an event were to occur, the United
States would be ill prepared on several fronts. The
primary concern is an inadequate supply of vaccine,
which is essential to preventing disease development in
exposed persons. Between 1997 and 2001, two companies were contracted to produce additional smallpox
vaccines for both military and civilian use. Through
these contracts, an additional 40 million doses would
be made available for civilian use by 2005. In the
meantime, studies are underway to determine if the
existing vaccines can be diluted in order to increase the
number of doses available for immediate use. Results
from a very small group of volunteers tested in 2000
found that at one-tenth strength, the existing smallpox
vaccines are approximately 70% effective. In late
2001, a new study began evaluating the effectiveness
of the vaccine at one-fifth strength.
In the event that smallpox is reintroduced into the
current population, it will be imperative that doctors
immediately recognize the symptoms and isolate the
individual to prevent further spread of the disease.
Prompt vaccination of any persons who had contact
GALE ENCYCLOPEDIA OF MEDICINE

Resources
PERIODICALS

Broad, William J. ‘‘U.S. Acts to Make Vaccines and Drugs
Against Smallpox.’’ The New York Times October 9,
2001: D1-2.
Miller, Judith, and Sheryl Gay Stolberg. ‘‘Sept. 11 Attaks
Led to Push for More Smallpox Vaccine.’’ The New
York Times October 22, 2001: A1.
OTHER

Hamre, John, Randy Larsen, Mark DeMier, General
Dennis Reimer, and Tara O’Toole. ‘‘Dark Winter.’’
ANSER Analytic Services Inc. [cited October 25, 2001].
<http://www.aha.org/Emergency/Readiness/
FieldLessons.asp>.
Henderson, D. A. ‘‘Smallpox: Clinical and Epidemiologic
Features.’’ In: Emerging Infectious Diseases 15, no. 4
(July-August 1999) [Online Journal]. [cited October 25,
2001]. <http://www.cdc.gov/ncidod/EID/vol5no4/
henderson.htm>.
Rotz, Lisa D., Debra A. Dotson, Inger K. Damon, and John
A. Becher. ‘‘Vaccinia (Smallpox) Vaccine
Recommendations of the Advisory Committee on
Immunization Practices (ACIP), 2001.’’ In: Morbidity
and Mortality Weekly Report 50, rr 10 (June 22, 2001):
1-25. [cited October 25, 2001]. <http://www.cdc.gov/
mmwr/preview/mmwrhtml/rr5010a1.htm>.

roof of the nose. This section of the nose called the
olfactory area is located just below the brain’s frontal
lobes.
In the olfactory area are millions of tiny olfactory
cells. Each cell contains about 12 cilia, tiny hairs that
extend into a mucus layer. The mucus moistens the
cilia. Mucus also catches odor molecules, while receptors in the cilia stimulate the molecules and send nerve
impulses to the brain.
Olfactory nerve fibers carry the impulse to two
olfactory bulbs located in the brain. Information is
processed in the bulbs and then sent to the cerebral
cortex. Once the transmission is inside the smell center
of the brain, a person experiences the sense of smell.
A person with a normal sense of smell (normosmia) is able to distinguish 10,000 odors. The sense of
smell stimulates salivary glands. As a result, smelling
disorders often affect the sense of taste. The olfactory
sense allows people to experience pleasurable odors
like the scent of roses. And smell is thought to contribute to sexual attraction.
A smelling disorder that affects the sense of smell
is generally not life-threatening. However, it can be
dangerous. Without a sense of smell, a person might
eat spoiled food. Lack of a sense of smell could pose a
health risk if a person has little appetite and fails to eat
enough. Furthermore, without a sense of smell, a person might not detect a gas leak or the smell of something burning. Loss of smell and the resulting loss of
taste may lead to depression.

Rosalyn Carson-DeWitt, MD
Types of smelling disorders

Smelling disorders
Definition
Smelling disorders are disturbances of the olfactory sense, which is known as the sense of smell. These
nasal dysfunctions range from the total loss of smell
(anosmia) to dysosmia, a distorted sense of smell.

Smelling disorders differ in the way that the sense
of smell is affected and how long a person has the
disorder. For example, anosmia, the loss of the sense
of smell, is often a temporary symptom of a cold or
flu. However, a head injury could cause permanent
anosmia. In addition, a head injury could produce
dysosmia, the distorted sense of smell that could
cause a person to hallucinate a foul odor.
Smelling disorders are categorized as:


Anosmia, the loss of the sense of smell. It is the most
common smelling disorder. This condition can be
temporary or permanent.



Dysosmia is a distorted sense of smell. A person
senses non-existent unpleasant odors. It can be
caused by medical and mental conditions.



Hyperosmia is an increased sensitivity to smell. It can
be a characteristic of someone with a neurotic or
histrionic personality.

Description
An awareness of how the olfactory system works
is helpful for understanding how smelling disorders
affect the sense of smell. People detect odors because
sensory receptors located in the nose carry smell sensations to the brain. The receptors, which are nerve cell
endings, are found in the mucous membrane in the
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3459

Smelling disorders

with the patient is also necessary to prevent additional
cases of smallpox from developing. Controlling and
containing spread of this disease is critical for prevention of a world-wide epidemic that would have a
devastating impact on current populations.

Smelling disorders





Hyposmia is the diminished sense of smell. This is
usually a temporary condition that a person may
experience after a case of acute influenza. Sometimes
this condition is referred to as partial anosmia.
Presbyosmia refers to the lessening or loss of the
olfactory sense that occurs when a person ages.



Head injury. If both olfactory nerves are torn during
a head injury, permanent anosmia results.



Medications such as antihistamines and decongestants, especially prolonged use of decongestants.



Drugs like amphetamines, estrogen, naphazoline,
phenothiazines, and resperine.



The aging process may cause the sense to lessen. In
most cases, there is no other obvious cause for the
disorder.



A tumor behind the nose or in the membranes surrounding the brain.



Lead poisoning.



Exposure to insecticides or other chemicals.



Radiation therapy.



Nervous disorders.



Idiopathic loss, which means there is no diagnosable
cause for the condition.

Smelling disorder demographics
Anosmia occurs in about 10% of head trauma
injuries, and head trauma is a leading cause of anosmia in young adults. In older adults, the disorder is
generally caused by viral infection. Aging may also
bring a loss of the sense of smell. In rare cases, anosmia
is inherited. It is a symptom of male hypogonadism
(Kallmann’s syndrome).
Olfactory hallucinations known as dysosmia are
generally associated with psychological conditions. In
some cases, people may believe they are the source of
foul odors.

Anosmia symptoms

Causes and symptoms
Anosmia is the most common type of smelling
disorder. Loss of the olfactory sense is generally caused
by nasal congestion or obstruction. Temporary partial
anosmia often occurs when a person has a cold, the flu,
or some types of rhinitis, especially hay fever (allergic
rhinitis). During these conditions, nasal mucus membranes become inflamed. Other causes for anosmia are:


Nasal polyps and other disorders that prevent air
from getting to the area in the nose where the smell
receptors are found. Hay fever or an allergy may
cause one or more polyps to show up.



Viral upper respiratory infection.



Atrophic rhinitis. This condition causes mucus membrane to waste away. The person may experience
some level of permanent anosmia. One symptom of
this condition is that a person expels a foul-smelling
discharge.

Most people with anosmia can distinguish salty,
sweet, bitter, and sour tastes since the tongue senses
these tastes. However, people with anosmia cannot
sense other tastes. Since taste is largely based on the
olfactory sense, people complain of losing the sense of
taste (ageusia).
Dysosmia
Infected nasal sinuses and damage to the olfactory
bulbs can cause dysosmia, the distorted sense of smell.
Head trauma can cause this disorder. Poor oral
hygiene can lead to dysosmia. In these cases, a person
may also find that disagreeable odors are accompanied by the sensing of unpleasant tastes. In addition,
brain-stem disease can cause smelling disorders. An
epileptic seizure can include olfactory hallucinations.
Mental conditions such as depression and schizophrenia may be accompanied by dysosmia. In addition, when people who are person severely dependent
on alcohol quit drinking, they may experience
dysosmia.



Hypertrophic rhinitis. Mucous membrane thickens,
covering the olfactory nerve endings. If not treated,
hypertrophic rhinitis can lead to permanent anosmia. This discharge could overpower other odors.



Cigarettes. Smoking aggravates the nose’s membrane
and intensifys nasal polyp symptoms.



A crooked nose or a deviated septum.

If a smelling disorder is a symptom of a mental
condition such as schizophrenia, diagnosis should be
part of treatment for that condition.



When the olfactory bulbs, tracts, or central connections are destroyed. This can occur in situations such
as head trauma, infections or nasal or sinus surgery.

When the condition is caused by a medical condition such as allergies or a viral infection, a person may
notice that the olfactory sense is impaired during that

3460

Diagnosis

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis of smelling disorders begins with a
health assessment to determine the cause of the olfactory impairment. The patient’s primary care doctor
will ask if the patient has a cold, allergies, sinusitis, or
an upper respiratory infection.
Treatment of a head injury or follow-up medical
appointment should address smelling disorders. In all
cases, discussion of the symptoms covers issues such
as when the smelling disorder started, if this has been
an ongoing problem, and whether the disorder is
becoming more intense. The assessment will include
questions about whether the patient can taste food
and if the disorder affects all odors or specific smells.
The patient will also be asked about medications
taken.
Physical examinations
The physical examination will include a thorough
inspection of the nose, nasopharynx, and the examination of the upper respiratory tract. The examination
could include sinus transillumination, placement of a
light on the face to help determine if sinuses are full.
Skull x rays may be required to determine the presence
of tumors in the nose or brain.
The patient may be referred to a neurologist;—an
ear, nose, and throat specialist;—or to a center that
specializes in treatment of smelling disorders.
Other diagnostic tests could be required. These
include:

Medical costs
The costs for diagnosis and treatment vary
because of the different types of smelling disorders,
the range of causes for olfactory dysfunction, and the
different types of treatment.
There are also differences in what health plans
require in terms of patient co-pay. A health plan
could cover treatments ranging from the initial
appointment with a primary care provider to the
surgery to remove brain tumors.
In addition, some health plans cover costs of treatment at specialized facilities like the Center for Smell
and Taste Disorders at the University of Colorado
Health Sciences Center in Denver. A series of tests
including a taste-and-smell test cost $250 in May
of 2001.

Treatment
Treating a condition that causes a smelling disorder can sometimes restore the olfactory sense.
Treatments for smelling disorders are as varied as the
olfactory dysfunctions. Treatment for smelling disorders ranges from lifestyle changes to surgery.
Treatment of mental conditions could affect the smelling disorder. In some cases, the disorder can’t be
treated, and the person must adjust to the loss of the
sense of smell. Anosmia associated with aging is not
treatable.
Basic treatments for anosmia



A CT scan (computed tomography scans) of the head.
Also known as a CAT scan, this process provides a
more detailed image than the x ray.



Olfactory nerve testing.

The sense of smell should return after a condition
like a cold or the flu ends. Decongestants such as
Sudafed help reduce congestion related to colds, allergies, and sinus conditions. Manufacturer’s dosage
recommendations should be followed. If anosmia is
related to excessive use of nasal decongestants, a person should discontinue use of those medications.



Nasal cytology, which involves the study of mucus
under a microscope.

Saline sprays can be used to clean the interior of
the nose.



Testing to determine the scope of smelling disorder.
A basic smell test involves the patient trying to
identify each one of a group of different odors. A
variation of this is a scratch-and-sniff test. The
patient may be asked to differentiate among concentrations of one odor. The alcohol sniff test that
involves use of a material soaked in isopropyl alcohol. Patients close their eyes and the doctor moves
around. Patients tell the doctor when they smell the
alcohol.

If smoking causes anosmia, a person should quit
smoking.



The patient may also take a taste test.

GALE ENCYCLOPEDIA OF MEDICINE

The sense of smell may return after treatment of
allergic or bacterial rhinitis and sinusitis. An over-thecounter antihistamine such as Actifed may provide
relief.
If allergies cause anosmia, adjustments should be
made to avoid allergens. If dust causes allergies, care
should be taken to clean areas such as the bedroom.
Antibiotics may be prescribed for infections.
3461

Smelling disorders

condition. If the smelling disorder continues after the
person is well, an appointment should be made with a
primarily health care provider.

Smelling disorders

Other medications prescribed for smelling disorders include steroids such as Prednisone. It should
only be used for a short time since longterm use
could lessen resistance to infection.
Surgical treatment
Removal of nasal polyps and benign tumors may
cause the sense of smell to return. Polyp removal is an
uncomplicated surgery. Generally, only a local anesthetic is needed.
Septoplasty straightens the nasal passage. It is
generally an outpatient surgery, with local or general
anesthesia required. Rhinoplasty straightens the structure of the nose. This surgery could be combined with
septoplasty.
Endoscopic sinus surgery opens sinus drainage
channels. This outpatient surgery is an option after a
person sees no improvement after trying treatments
such as medications.
Surgical treatment may not be effective in conditions that result in the destruction of the olfactory
nerve or its central passages. However, regeneration
of those tissues may cause the sense to return.
Enhancing taste
Without a sense of smell, most people can still
taste salt and flavors that are sweet, sour, and bitter.
People with anosmia could distinguish other tastes by
adding spices such as pepper to food. These spices
stimulate facial nerves that also sense flavors.

Alternative treatment
Alternative treatments for smelling disorder center around the theory that zinc supplements help
improve the sense of smell. The supplement is said to
be effective when the olfactory sense is impaired by
conditions such as a head injury or an upper respiratory infection. A person should take 50 mg of zinc
picolinate each day after eating. This procedure
might be effective in the case of head injury.
However, it may be several months before results are
seen. Acupuncture may also produce results.
If polyps cause a smelling disorder, a change in
diet could be helpful. A person should avoid dairy
products, take supplements such as garlic, and follow
other recommendations from a health care practitioner. A daily dosage of 5,000–10,000 mg of vitamin
C could cut back on the amount of polyps. Vitamins
should not be taken all at once. A multi-vitamin and
mineral complex could also help.
3462

KEY TERMS
Histrionic—A behavior characterized by an excitable nature and the constant desire for stimulation.
Nasopharynx—The passage that connects the nasal
cavity to the top of the throat.
Neurotic—Behavior characterized by neurosis,
mental functional orders with symptoms such as
anxiety, depression, compulsions, and phobias.
Polyp—A benign growth in areas such as the nasal
passage.
Rhinitis—The inflammation of the mucous membrane in the nose.
Septum—A sheet of cartilage and bone that separates the nostrils.
Sinusitis—Inflammation of the paranasal sinuses
because of allergic reactions or viral, bacterial, or
functional infections.

Prognosis
In cases where smelling disorders are treatable, the
outcome is positive because the olfactory sense is
restored. In those cases where the sense of smell is
lost, the person must make adjustments to adapt to
life without that sense. Those adjustments include
using spices like pepper to stimulate tastebuds.
Since a person with anosmia can no longer smell
food to determine whether it is safe to eat, care should
be taken. The person who lives with other people can
ask them if food smells fresh. People who live alone
should discard food if there is a chance that it has
spoiled. Other home safety measures include installing
smoke alarms and gas detectors. Cooking on an electric stove is preferable to a gas stove.
Furthermore, people with smelling disorders can
find support groups. These are often associated with
smell and taste clinics. In addition, there are on-line
bulletin board where people can share experiences.
One site contains descriptions of how things smell.
Those words provide a connection to a missing sense
in the same way that sign language allows the hearingimpaired to understand the spoken word.

Prevention
Not all causes of smelling disorders can be prevented. However, people with a disorder should not
smoke and should ask those around them not to
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Watson, Lyall. Jacob’s Organ and the Remarkable Sense of
Smell. New York: W. W. Norton &Company, 2000.
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery. One Prince St., Alexandria, VA 23314-3357.
(703) 836-4444. <http://www.ent.org>.
Center for Taste and Smell Disorders. University of
Colorado Health Sciences Center, 4200 E, Ninth Ave.,
Denver, CO 80262. (303) 315-5660.
<http://www.hsc.colorado.edu>.
U.S. Department of Health and Human Services. 200
Independence Avenue, SW, Washington, DC
20201.(877) 696-6775. <http://www.hhs.gov>.

Liz Swain

Smoke inhalation
Definition
Smoke inhalation is breathing in the harmful
gases, vapors, and particulate matter contained in
smoke.

Causes and symptoms
The harmful materials given off by combustion
injure the airways and lungs in three ways: heat
damage, tissue irritation, and oxygen starvation of
tissues (asphyxiation). Signs of heat damage are singed
nasal hairs, burns around and inside the nose and
mouth, and internal swelling of the throat. Tissue
irritation of the throat and lungs may appear as
noisy breathing, coughing, hoarseness, black or gray
spittle, and fluid in the lungs. Asphyxiation is apparent from shortness of breath and blue-gray or cherryred skin color. In some cases, the patient may not be
conscious or breathing.

Diagnosis
In addition to looking for the signs of heat damage,
tissue irritation, and asphyxiation, the physician will
assess the patient’s breathing by the respiratory rate
(number of breaths per minute) and motion of the
chest as the lungs inflate and deflate. The patient’s
circulation is also evaluated by the pulse rate (number
of heartbeats per minute) and blood pressure. Blood
tests will indicate the levels of oxygen and byproducts of
poisonous gases. Chest x rays are too insensitive to
show damage to delicate respiratory tissues, but can
show fluid in the lungs (pulmonary edema).
The physician may perform a bronchoscopy, a
visual examination in which the airways and lungs
are seen through a fiber optic tube inserted down the
patient’s windpipe (trachea). Other pulmonary function tests may be performed to measure how efficiently
the lungs are working.

Treatment
Description
Smoke inhalation typically occurs in victims or
firefighters caught in structural fires. However, cigarette smoking also causes similar damage on a smaller
scale over a longer period of time. People who are
trapped in fires may suffer from smoke inhalation
independent of receiving skin burns; however, the
incidence of smoke inhalation increases with the percentage of total body surface area burned. Smoke
inhalation contributes to the total number of firerelated deaths each year for several reasons: the
damage is serious; its diagnosis is not always easy
and there are no sensitive diagnostic tests; and
patients may not show symptoms until 24–48 hours
after the event. Children under age 11 and adults over
age 70 are most vulnerable to the effects of smoke
inhalation.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment will vary with the severity of the
damage caused by smoke inhalation. The primary
focus of treatment is to maintain an open airway and
provide an adequate level of oxygen. If the airway is
open and stable, the patient may be given high-flow
humidified 100% oxygen by mask. If swelling of the
airway tissues is closing off the airway, the patient may
require the insertion of an endotracheal tube to artificially maintain an open airway.
Oxygen is often the only medication necessary.
However, patients who have a cough with wheezing
(bronchospasm), indicating that the bronchial airways
are narrowed or blocked, may be given a bronchodilator to relax the muscles and increase ventilation.
There are also antidotes for specific poisonous gases
in the blood; dosage is dependent upon the level indicated by blood tests. Antibiotics are not given until
3463

Smoke inhalation

smoke. Those with smelling disorders related to allergies should be taken to avoid allergens. Since head
trauma injuries can lead to smelling disorders, people
should wear protective helmets when bicycling or participating in sports like football.

Smoking-cessation drugs

Prevention

KEY TERMS
Asphyxiation—Oxygen starvation of tissues.
Chemicals such as carbon monoxide prevent the
blood from carrying sufficient oxygen to the brain
and other organs. As a result, the person may lose
consciousness, stop breathing, and die without
artificial respiration (assisted breathing) and other
means of elevating the blood oxygen level.
Hyperbaric oxygen therapy—Pure oxygen is administered to the patient in a special chamber at three
times the normal atmospheric pressure. The patient
gets more oxygen faster to overcome severe
asphyxiation.
Pulmonary—Pertaining to the lungs.
Pulmonary edema—The filling of the lungs with
fluid as the body’s response to injury or infection.

Smoke inhalation is best avoided by preventing
structural fires. This includes inspection of wiring, safe
use and storage of flammable liquids, and maintenance of clean, well-ventilated chimneys, wood stoves,
and space heaters. Properly placed and working
smoke detectors in combination with rapid evacuation
plans will minimize a person’s exposure to smoke in
the event of a fire. When escaping a burning building,
a person should move close to the floor where there is
more cool, clear air to breathe because hot air rises,
carrying gases and particulate matter upward. Finally,
firefighters should wear proper protective gear.
Resources
OTHER

Johnson, Norma Jean. ‘‘Smoke Inhalation.’’ eMedicine
World Medical Library. <http://
www.emedicine.com>.

Bethany Thivierge
sputum and blood cultures confirm the presence of a
bacterial infection.
In institutions where it is available, hyperbaric
oxygen therapy may be used to treat smoke inhalation
resulting in severe carbon monoxide or cyanide poisoning. This treatment requires a special chamber in
which the patient receives pure oxygen at three times
the normal atmospheric pressure, thus receiving more
oxygen faster to overcome loss of consciousness,
altered mental state, cardiovascular dysfunction, pulmonary edema, and severe neurological damage.

Alternative treatment
Botanical medicine can help to maintain open airways and heal damaged mucous membranes. It can
also help support the entire respiratory system.
Acupuncture and homeopathic treatment can provide
support to the whole person who has suffered a traumatic injury such as smoke inhalation.

Prognosis
Although the outcome depends of the severity of
the smoke inhalation and the severity of any accompanying burns or other injuries, with prompt medical
treatment, the prognosis for recovery is good.
However, some patients may experience chronic
pulmonary problems following smoke inhalation,
and those with asthma or other chronic respiratory
conditions prior to smoke inhalation may find their
original conditions have been aggravated by the inhalation injury.
3464

Smoking-cessation drugs
Definition
Smoking cessation drugs are medicines that help
people stop smoking cigarettes or using other forms of
tobacco.

Purpose
People who smoke cigarettes or use other forms of
tobacco often have a difficult time when they try to
stop. The difficulty is partly psychological; they get in
the habit of using tobacco at certain times of day or
while they are doing certain things, such as having a
cup of coffee or reading the newspaper. But the habit
is also hard to break for physical reasons. Tobacco
contains nicotine, a drug that is as addictive as
cocaine or heroin. Of those who have ever tried even
a single cigarette, about a third will become nicotinedependent. A person who is addicted to nicotine has
withdrawal symptoms, such as irritability, anxiety,
difficulty concentrating, and craving for tobacco
when he or she stops using tobacco.
Some people can stop smoking through willpower alone, but most do better if they have support
from friends, family, a physician or pharmacist, or a
formal stop-smoking program. Heavy tobacco users
GALE ENCYCLOPEDIA OF MEDICINE

Smoking-cessation drugs

The nicotine patch brand Nicoderm. (Fieldmark Publications. Reproduced by permission.)

may find that smoking cessation products also help
by easing their withdrawal symptoms. Most smoking
cessation products contain nicotine, but the nicotine
is delivered in small, steady doses spread out over
many hours. In contrast, when a person inhales a
cigarette, nicotine enters the lungs and then travels
to the brain within seconds, delivering the ‘‘rush’’
that smokers come to crave. Another difference is
that smoking cessation products do not contain the
tar, carbon monoxide, and other toxins that make
cigarettes so harmful to people’s health. According
to one Canadian study, tobacco smoke contains over
40 different chemicals known to cause cancer.
The importance of smoking cessation is reflected in
legal penalties against the tobacco industry for its longstanding denial of the harm caused by tobacco
GALE ENCYCLOPEDIA OF MEDICINE

products. Recent legal findings against the tobacco
industry have led to legislation in three states concerning lawsuits against the industry. In Florida, state agencies can sue on behalf of Medicaid recipients for
repayment of benefits. Maryland allows the use of statistical analysis in lawsuits against tobacco companies.
In Vermont, the state can bring direct lawsuits against
tobacco manufacturers to recover Medicaid benefits for
tobacco-related illnesses paid after April 1998.
Nineteen states (Alabama, Alaska, Connecticut,
Florida,
Hawaii,
Louisiana,
Maryland,
Massachusetts, Minnesota, Mississippi, Montana,
New Hampshire, New York, Rhode Island, Texas,
Vermont, Virginia, Washington, and Wisconsin)
have set aside as of 2001 a portion of their money
from tobacco settlements to smoking prevention
programs.
3465

Smoking-cessation drugs

Description
Nicotine replacement products
Smoking cessation drugs that contain nicotine are
also called nicotine substitution products or nicotine
replacement therapy. There are four forms approved
by the Food and Drug Administration (FDA) as of
2001–chewing gum, skin patch, nasal spray, and inhaler. The nasal spray and inhaler are available only with
a prescription, but the gum and some brands of the
patch can be bought over the counter (without a
prescription). People who buy the nonprescription
products should check with a physician before starting
to use them. The patches are sold under the brand
names Nicotrol, Nicoderm CQ, and Habitrol (prescription only). The gum is sold under the brand name
Nicorette. The nasal spray and inhaler are marketed
as Nicotrol NS and Nicotrol respectively. The costs of
these products are about $30 for a box of 48 pieces of
the gum and about $30 per week for the patches.
Other medications
Another type of smoking cessation drug, bupropion
(Zyban), also reduces craving and withdrawal symptoms, although it is not a nicotine replacement product.
Bupropion is an antidepressant medication that is
thought to help people stop smoking by mimicking
some of the effects of tobacco on brain tissue.
Bupropion can be used together with nicotine replacement products; several studies indicate that the combination helps more smokers quit than either method by itself.
Buspirone (BuSpar) is a tranquilizer that appears
to be effective in helping smokers deal with feelings of
anxiety resulting from tobacco withdrawal.
Alternative approaches
Other approaches that have been used to help smokers quit include hypnosis and acupuncture. The evidence
for the usefulness of hypnosis is largely anecdotal; it
appears to be most helpful when used in combination
with nicotine replacement products or bupropion.
Although acupuncture has been used in Western countries since the 1970s to help people quit smoking, it does
not appear to be particularly effective in this regard. A
British study that was published in 1999 found that smokers who received acupuncture did not have a higher quit
rate than those who received only sham acupuncture.

Recommended dosage
The recommended dosage of nicotine replacement
products depends on the method of administration.
3466

Each form of this medicine comes with detailed instructions for its use. Following directions exactly is very
important. For example, nicotine gum should not be
chewed like regular chewing gum. It must be chewed
very slowly until it has a slight taste or causes a slight
tingling sensation in the mouth; then ‘‘parked’’ between
the cheek and gum until the taste and tingling goes
away; then chewed and parked in the same way for
about 30 minutes. Nicotine patches and other products
also must be used correctly to be effective. Some
patches are meant to be worn only during the day and
removed at night; others are worn 24 hours a day.
Smokers who are heavily dependent on nicotine
may want to ask their doctors about using a combination of nicotine replacement products. Studies done
between 1995 and 2000 indicate that combining the
transdermal patch with either the gum or the nasal
spray helps more smokers quit than any of the three
products by themselves. It is thought that the higher
success rate is due to the different rates of speed at
which these products deliver nicotine to the body. The
nasal spray delivers nicotine very rapidly, and can be
used to relieve intense cravings at times of the day
when the smoker is accustomed to having a cigarette,
while the patch delivers a smaller dosage of nicotine to
the body at a steadier rate.

Precautions
Seeing a physician regularly while using smoking
cessation drugs is important. The physician will check
to make sure the medicine is working as it should and
will watch for unwanted side effects.
Seeing a physician regularly while using smoking
cessation drugs is important. The physician will check
to make sure the medicine is working as it should and
will watch for unwanted side effects.


nausea



vomiting



severe pain in the stomach or abdomen



severe diarrhea



severe dizziness



fainting



convulsions (seizures)



low blood pressure



fast, weak, or irregular heartbeat



hearing or vision problems



severe breathing problems



severe watering of the mouth or drooling
GALE ENCYCLOPEDIA OF MEDICINE

Smoking-cessation drugs

Drug reservoir
Foil backing

Adhesive
Membrane
The nicotine patch is a type of transepidermal patch designed to deliver nicotine, the addictive substance contained in
cigarettes, directly through the skin and into the blood stream. The patch contains a drug reservoir sandwiched between a
nonpermeable back layer and a permeable adhesive layer that attaches to the skin. The drug leeches slowly out of the reservoir,
releasing small amounts of the drug at a constant rate for up to 24 hours. (Illustration by Electronic Illustrators Group.)



cold sweat



severe headache



confusion



severe weakness

Keep these drugs, including thrown-away patches
and gum–out of the reach of children and pets. Even a
small amount of nicotine can seriously harm a child or
animal.
Nicotine in any form should not be used during
pregnancy, as it may harm the fetus or cause miscarriage. Women who may become pregnant should use
effective birth control while taking smoking cessation
drugs. Women who become pregnant while taking this
GALE ENCYCLOPEDIA OF MEDICINE

medicine should stop taking it immediately and check
with their physicians.
Nicotine passes into breast milk and may cause
problems for nursing babies. Women who are breastfeeding and want to use smoking cessation drugs may
need to stop breastfeeding during treatment.
Anyone who has had unusual reactions to nicotine in the past should let his or her physician know
before using a smoking cessation drug. The physician
should also be told about any allergies to foods, dyes,
preservatives, or other substances. People who have
had a rash or irritation from adhesive bandages
should check with a physician before using a nicotine
patch.
3467

Smoking-cessation drugs

KEY TERMS
Acupuncture—A Chinese medical practice that
treats illness or addictions by the insertion of very
thin steel needles at specified points along the
body’s energy channels.
Bupropion—An antidepressant medication given
to smokers for nicotine withdrawal symptoms. It is
sold under the trade name Zyban.
Buspirone—An antianxiety medication that is also
given for withdrawal symptoms. It is sold under the
trade name BuSpar.

The wheals on the arm of this patient was caused by an
allergic reaction to nicotine patches used to help subdue
the urge to smoke. (Custom Medical Stock Photo. Reproduced
by permission.)

Nicotine—A colorless, oily chemical found in
tobacco that makes people physically dependent
on smoking. It is poisonous in large doses.
Withdrawal symptoms—A group of physical or
mental symptoms that may occur when a person
suddenly stops using a drug on which he or she has
become dependent.

tranquilizers do, patients should still use alcohol cautiously if they are taking buspirone.
Smoking cessation patches, gum, and other products may make certain medical problems worse.
Before using a smoking cessation drug, people with
any of these medical problems should make sure their
physicians are aware of their conditions:


heart or blood vessel disease



high blood pressure



diabetes



overactive thyroid



skin rash or irritation



stomach ulcer



pheochromocytoma (pcc) (a tumor of the adrenal
medulla)



dental problems or mouth sores



sore throat



jaw pain or temporomandibular joint disorder
(TMJ)

There are also precautions to take with bupropion
and buspirone. Bupropion should not be taken by
patients with a history of seizures, high blood pressure,
anorexia, or bulimia nervosa. People taking buspirone
should be careful about driving or operating heavy
machinery until they can tell whether the drug makes
them drowsy as a side effect. Although buspirone does
not interact with alcohol as intensely as most
3468

Side effects
Each type of smoking cessation product may
cause minor side effects that usually go away as the
body adjusts to the drug. These usually do not need
medical attention unless they continue or they interfere with normal activities. For example, nicotine gum
may cause belching, jaw aches, or sore mouth or
throat. Nicotine patches may cause redness, itching,
or burning where the patch is applied. The nasal spray
may irritate the nose and sinuses, while the inhaler
may cause throat irritation or coughing.
If nicotine gum injures the mouth, teeth, or dental
work, check with a physician as soon as possible.
Other side effects are possible. Anyone who has unusual symptoms while using smoking cessation drugs
should get in touch with his or her physician.
The side effects of bupropion include dry mouth
and difficulty sleeping. The possible side effects of
buspirone include headaches and drowsiness.

Interactions
People taking certain drugs may need to change
their doses when they stop smoking. Anyone who uses
a smoking cessation drug should let the physician
know all other medicines he or she is taking and
GALE ENCYCLOPEDIA OF MEDICINE



insulin



airway opening drugs (bronchodilators) such as aminophylline (Somophyllin), oxtriphylline (Choledyl)
or theophylline (Somophyllin-T)



opioid (narcotic) pain relievers such as propoxyphene (Darvon)



the beta blocker propranolol (Inderal)

Other drugs may also interact with smoking cessation drugs. Be sure to check with a physician or pharmacist before combining smoking cessation drugs
with any other prescription or nonprescription (overthe-counter) medicine.
Bupropion should not be used by patients who are
also taking monoamine oxidase inhibitor (MAOI)
medications. These include such drugs as furazolidone, isocarboxazid, and phenelzine. Bupropion may
also interact with phenytoin, carbamazepine, and
levodopa. Buspirone also interacts with MAOIs, as
well as with trazadone and haloperidol.
Resources
BOOKS

American Cancer Society. Quitting Smoking. New York:
American Cancer Society, 2000. <http://www.cancer.org/tobacco/quitting>.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Smoking Cessation.’’ The Merck Manual of Diagnosis
and Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
United States Public Health Service. You Can Quit Smoking.
Consumer Guide, June 2000. Government Publications
Clearinghouse, P.O. Box 8547, Silver Spring, MD
20907. <http:www.surgeongeneral.gov/tobacco/
consquits.htm>.
PERIODICALS

Okuyemi, K. S., et al. ‘‘Pharmacotherapy of Smoking
Cessation.’’ Archives of Family Medicine 9 (March
2000): 270-281.
ORGANIZATIONS

American Association for Respiratory Care. 11030 Ables
Lane, Dallas, TX 75229. <http://www.aarc.org>.
American Cancer Society (ACS). 1599 Clifton Road, NE,
Atlanta, GA 30329. (404) 320-3333 or (800) ACS-2345.
Fax: (404) 329-7530. <http://www.cancer.org>.
American Lung Association. 1740 Broadway, 14th Floor,
New York, NY 10019. (212) 315-8700 or (800) 586-4872
(LUNG USA).
Office on Smoking and Health. Centers for Disease Control
and Prevention. Mailstop K-50, 4770 Buford Highway
GALE ENCYCLOPEDIA OF MEDICINE

NE, Atlanta, GA 30341-3724. (800) 232-1311. <http://
www.cdc.gov/tobacco/>.
OTHER

de Guia, Nicole. Rethinking Stop-Smoking Medications:
Myths and Facts. Position paper prepared for the
Ontario Medical Association (OMA). OMA Health
Policy Department, Ontario, Canada, June 1999.
Questions and Answers About Finding Smoking Cessation
Services. Fact Sheet, National Cancer Institute.
<http://www.nci.nih.gov>.
Smoking Cessation Guidelines. Agency for Health Care
Policy and Research Publications Clearinghouse. PO
Box 8547, Silver Spring, MD 20907.

Rebecca J. Frey, PhD

Smoking
Definition
Smoking is the inhalation of the smoke of burning
tobacco encased in cigarettes, pipes, and cigars.
Casual smoking is the act of smoking only occasionally, usually in a social situation or to relieve stress.
A smoking habit is a physical addiction to tobacco
products. Many health experts now regard habitual
smoking as a psychological addiction, too, and one
with serious health consequences.

Description
The U.S. Food and Drug Administration has
asserted that cigarettes and smokeless tobacco
should be considered nicotine delivery devices.
Nicotine, the active ingredient in tobacco, is inhaled
into the lungs, where most of it stays. The rest passes
into the bloodstream, reaching the brain in about 10
seconds and dispersing throughout the body in about
20 seconds.
Depending on the circumstances and the amount
consumed, nicotine can act as either a stimulant or
tranquilizer. This can explain why some people report
that smoking gives them energy and stimulates their
mental activity, while others note that smoking
relieves anxiety and relaxes them. The initial ‘‘kick’’
results in part from the drug’s stimulation of the adrenal glands and resulting release of epinephrine into the
blood. Epinephrine causes several physiological
changes—it temporarily narrows the arteries, raises
the blood pressure, raises the levels of fat in the
blood, and increases the heart rate and flow of blood
3469

Smoking

should ask whether the doses need to be changed.
Examples of drugs that may be affected when a person
stops smoking are:

Smoking

from the heart. Some researchers think epinephrine
contributes to smokers’ increased risk of high blood
pressure.
Nicotine, by itself, increases the risk of heart
disease. However, when a person smokes, he or she
is ingesting a lot more than nicotine. Smoke from a
cigarette, pipe, or cigar is made up of many additional toxic chemicals, including tar and carbon
monoxide. Tar is a sticky substance that forms into
deposits in the lungs, causing lung cancer and
respiratory distress. Carbon monoxide limits the
amount of oxygen that the red blood cells can convey
throughout your body. Also, it may damage the inner
walls of the arteries, which allows fat to build up
in them.
Besides tar, nicotine, and carbon monoxide,
tobacco smoke contains 4,000 different chemicals.
More than 200 of these chemicals are known be
toxic. Nonsmokers who are exposed to tobacco
smoke also take in these toxic chemicals. They inhale
the smoke exhaled by the smoker as well as the more
toxic sidestream smoke—the smoke from the end of
the burning cigarette, cigar, or pipe.
Here’s why sidestream smoke is more toxic than
exhaled smoke: When a person smokes, the smoke
he or she inhales and then breathes out leaves harmful deposits inside the body. But because lungs partially cleanse the smoke, exhaled smoke contains
fewer poisonous chemicals. That’s why exposure
to tobacco smoke is dangerous even for a
nonsmoker.

Causes and symptoms
No one starts smoking to become addicted to
nicotine. It isn’t known how much nicotine may be
consumed before the body becomes addicted.
However, once smoking becomes a habit, the smoker
faces a lifetime of health risks associated with one of
the strongest addictions known to man.
About 70% of smokers in the United States would
like to quit; in any given year, however, only about
3.6% of the country’s 47 million smokers quit
successfully.
Although specific genes have not yet been identified as of 2003, researchers think that genetic factors
contribute substantially to developing a smoking
habit. Several twin studies have led to estimates of
46–84% heritability for smoking. It is thought that
some genetic variations affect the speed of nicotine
metabolism in the body and the activity level of nicotinic receptors in the brain.
3470

Symptoms That Occur After Quitting Smoking

Symptom

Cause

Duration

Relief

Craving for
cigarette

nicotine craving

distract yourself
with other activity

Irritability,
impatience

nicotine craving

first week
can linger
for
months
2 to 4
weeks

Insomnia

nicotine craving
temporarily
reduces deep
sleep
lack of nicotine
stimulation
lack of nicotine
stimulation
cigarettes craving confused
hunger pangs

2 to 4
weeks

Body ridding
itself of mucus
in lungs and
airways
Intestinal
movement
decreases with
lack of nicotine

Several
weeks

Fatigue
Lack of
concentration
Hunger

Coughing,
dry throat,
nasal drip
Constipation,
gas

2 to 4
weeks
A few
weeks
Up to
several
weeks

1 to 2
weeks

Exercise, relaxation techniques,
avoid caffeine
Avoid caffeine
after 6 PM
relaxation techniques; exercise
Nap
Reduce workload; avoid stress
Drink water or
low calorie
drinks; eat lowcalorie snacks
Drink plenty of
fluids; use cough
drops
Drink plenty of
fluids; add fiber
to diet; exercise

Smoking risks
Smoking is recognized as the leading preventable
cause of death, causing or contributing to the deaths of
approximately 430,700 Americans each year. Anyone
with a smoking habit has an increased chance of lung,
cervical, and other types of cancer; respiratory diseases such as emphysema, asthma, and chronic bronchitis; and cardiovascular disease, such as heart attack,
high blood pressure, stroke, and atherosclerosis (narrowing and hardening of the arteries). The risk of
stroke is especially high in women who take birth
control pills.
Smoking can damage fertility, making it harder to
conceive, and it can interfere with the growth of the
fetus during pregnancy. It accounts for an estimated
14% of premature births and 10% of infant deaths.
There is some evidence that smoking may cause impotence in some men.
Because smoking affects so many of the body’s
systems, smokers often have vitamin deficiencies and
suffer oxidative damage caused by free radicals. Free
radicals are molecules that steal electrons from other
GALE ENCYCLOPEDIA OF MEDICINE

Smoking is recognized as one of several factors
that might be related to a higher risk of hip fractures in
older adults.
Studies reveal that the more a person smokes, the
more likely he is to sustain illnesses such as cancer,
chronic bronchitis, and emphysema. But even smokers
who indulge in the habit only occasionally are more
prone to these diseases.
Some brands of cigarettes are advertised as ‘‘low
tar,’’ but no cigarette is truly safe. If a smoker switches
to a low-tar cigarette, he is likely to inhale longer and
more deeply to get the chemicals his body craves. A
smoker has to quit the habit entirely in order to
improve his health and decrease the chance of disease.
Though some people believe chewing tobacco is
safer, it also carries health risks. People who chew
tobacco have an increased risk of heart disease and
mouth and throat cancer. Pipe and cigar smokers have
increased health risks as well, even though these smokers generally do not inhale as deeply as cigarette
smokers do. These groups haven’t been studied as
extensively as cigarette smokers, but there is evidence
that they may be at a slightly lower risk of cardiovascular problems but a higher risk of cancer and various
types of circulatory conditions.
Recent research reveals that passive smokers, or
those who unavoidably breathe in second-hand
tobacco smoke, have an increased chance of many
health problems such as lung cancer and asthma, and
in children, sudden infant death syndrome.
Smokers’ symptoms
Smokers are likely to exhibit a variety of symptoms that reveal the damage caused by smoking. A
nagging morning cough may be one sign of a tobacco
habit. Other symptoms include shortness of breath,
wheezing, and frequent occurrences of respiratory illness, such as bronchitis. Smoking also increases fatigue and decreases the smoker’s sense of smell and
taste. Smokers are more likely to develop poor circulation, with cold hands and feet and premature wrinkles.
Sometimes the illnesses that result from smoking
come on silently with little warning. For instance,
coronary artery disease may exhibit few or no symptoms. At other times, there will be warning signs, such
as bloody discharge from a woman’s vagina, a sign of
cancer of the cervix. Another warning sign is a hacking
cough, worse than the usual smoker’s cough, that
brings up phlegm or blood—a sign of lung cancer.
GALE ENCYCLOPEDIA OF MEDICINE

Withdrawal symptoms
A smoker who tries to quit may expect one or
more of these withdrawal symptoms: nausea, constipation or diarrhea, drowsiness, loss of concentration,
insomnia, headache, nausea, and irritability.

Diagnosis
It’s not easy to quit smoking. That’s why it may
be wise for a smoker to turn to his physician for help.
For the greatest success in quitting and to help with
the withdrawal symptoms, the smoker should talk
over a treatment plan with his doctor or alternative
practitioner. He should have a general physical examination to gauge his general health and uncover any
deficiencies. He should also have a thorough evaluation for some of the serious diseases that smoking can
cause.

Treatment
Research shows that most smokers who want to
quit benefit from the support of other people. It helps
to quit with a friend or to join a group such as those
organized by the American Cancer Society. These
groups provide support and teach behavior modification methods that can help the smoker quit. The smoker’s physician can often refer him to such groups.
Other alternatives to help with the withdrawal
symptoms of kicking the habit include nicotine replacement therapy in the form of gum, patches, nasal
sprays, and oral inhalers. These are available by prescription or over the counter. A physician can provide
advice on how to use them. They slowly release a small
amount of nicotine into the bloodstream, satisfying
the smoker’s physical craving. Over time, the amount
of gum the smoker chews is decreased and the amount
of time between applying the patches is increased. This
helps wean the smoker from nicotine slowly, eventually beating his addiction to the drug. But there’s
one important caution: If the smoker lights up while
taking a nicotine replacement, a nicotine overdose
may cause serious health problems.
The prescription drug Zyban (bupropion hydrochloride) has shown some success in helping smokers
quit. This drug contains no nicotine, and was originally developed as an antidepressant. It isn’t known
exactly how bupropion works to suppress the desire
for nicotine. A five-year study of bupropion reported
in 2003 that the drug has a very good record for safety
and effectiveness in treating tobacco dependence. Its
most common side effect is insomnia, which can also
result from nicotine withdrawal.
3471

Smoking

molecules, turning the other molecules into free radicals and destabilizing the molecules in the body’s cells.

Smoking

Researchers are investigating two new types of
drugs as possible treatments for tobacco dependence
as of 2003. The first is an alkaloid known as 18-methoxycoronaridine (18-MC), which selectively blocks
the nicotinic receptors in brain tissue. Another
approach involves developing drugs that inhibit the
activity of cytochrome P450 2A6 (CYP2A6), which
controls the metabolism of nicotine.

Expected results
Research on smoking shows that most smokers
desire to quit. But smoking is so addictive that fewer
than 20% of the people who try ever successfully kick
the habit. Still, many people attempt to quit smoking
over and over again, despite the difficulties—the cravings and withdrawal symptoms, such as irritability
and restlessness.
For those who do quit, the benefits to health are
well worth the effort. The good news is that once a
smoker quits the health effects are immediate and dramatic. After the first day, oxygen and carbon monoxide
levels in the blood return to normal. At two days, nerve
endings begin to grow back and the senses of taste and
smell revive. Within two weeks to three months, circulation and breathing improve. After one year of not
smoking, the risk of heart disease is reduced by 50%.
After 15 years of abstinence, the risks of health problems from smoking virtually vanish. A smoker who
quits for good often feels a lot better too, with less
fatigue and fewer respiratory illnesses.

Alternative treatment
There are a wide range of alternative treatments
that can help a smoker quit the habit, including hypnotherapy, herbs, acupuncture, and meditation. For
example, a controlled trial demonstrated that selfmassage can help smokers crave less intensely, smoke
fewer cigarettes, and in some cases completely give
them up.
Hypnotherapy
Hypnotherapy helps the smoker achieve a trancelike state, during which the deepest levels of the mind
are accessed. A session with a hypnotherapist may
begin with a discussion of whether the smoker really
wants to and truly has the motivation to stop smoking.
The therapist will explain how hypnosis can reduce the
stress-related symptoms that sometimes come with
kicking the habit.
Often the therapist will discuss the dangers of
smoking with the patient and begin to ‘‘reframe’’
3472

the patient’s thinking about smoking. Many smokers
are convinced they can’t quit, and the therapist can
help persuade them that they can change this behavior. These suggestions are then repeated while the
smoker is under hypnosis. The therapist may also
suggest while the smoker is under hypnosis that his
feelings of worry, anxiety, and irritability will
decrease.
In a review of 17 studies of the effectiveness of
hypnotherapy, the percentage of people treated by
hypnosis who still were not smoking after six months
ranged from 4–8%. In programs that included several
hours of treatment, intense interpersonal interaction,
individualized suggestions, and follow-up treatment,
success rates were above 50%.
Aromatherapy
One study demonstrated that inhaling the vapor
from black pepper extract can reduce symptoms associated with smoking withdrawal. Other essential oils
can be used for relieving the anxiety a smoker often
experiences while quitting.
Herbs
A variety of herbs can help smokers reduce their
cravings for nicotine, calm their irritability, and even
reverse the oxidative cellular damage done by smoking. Lobelia, sometimes called Indian tobacco, has
historically been used as a substitute for tobacco. It
contains a substance called lobeline, which decreases
the craving for nicotine by bolstering the nervous
system and calming the smoker. In high doses, lobelia
can cause vomiting, but the average dose—about 10
drops per day—should pose no problems.
Herbs that can help relax a smoker during withdrawal include wild oats and kava kava.
To reduce the oral fixation supplied by a nicotine
habit, a smoker can chew on licorice root—the plant,
not the candy. Licorice is good for the liver, which is a
major player in the body’s detoxification process.
Licorice also acts as a tonic for the adrenal system,
which helps reduce stress. And there’s an added benefit: If a smoker tries to light up after chewing on
licorice root, the cigarette tastes like burned
cardboard.
Other botanicals that can help repair free-radical
damage to the lungs and cardiovascular system are
those high in flavonoids, such as hawthorn, gingko
biloba, and bilberry, as well as antioxidants such as
vitamin A, vitamin C, zinc, and selenium.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS

This ancient Chinese method of healing is used
commonly to help beat addictions, including smoking.
The acupuncturist will use hair-thin needles to stimulate the body’s qi, or healthy energy. Acupuncture is a
sophisticated treatment system based on revitalizing
qi, which supposedly flows through the body in
defined pathways called meridians. During an addiction like smoking, qi isn’t flowing smoothly or gets
stuck, the theory goes.

Antioxidant—Any substance that reduces the
damage caused by oxidation, such as the harm
caused by free radicals.
Chronic bronchitis—A smoking-related respiratory
illness in which the membranes that line the
bronchi, or the lung’s air passages, narrow over
time. Symptoms include a morning cough that
brings up phlegm, breathlessness, and wheezing.
Cytochrome—A substance that contains iron and
acts as a hydrogen carrier for the eventual release of
energy in aerobic respiration.

Points in the ear and feet are stimulated to help the
smoker overcome his addiction. Often the acupuncturist will recommend keeping the needles in for five to
seven days to calm the smoker and keep him balanced.

Emphysema—An incurable, smoking-related disease, in which the air sacs at the end of the lung’s
bronchi become weak and inefficient. People with
emphysema often first notice shortness of breath,
repeated wheezing and coughing that brings up
phlegm.

Vitamins
Smoking seriously depletes vitamin C in the body
and leaves it more susceptible to infections. Vitamin C
can prevent or reduce free-radical damage by acting as
an antioxidant in the lungs. Smokers need additional C,
in higher dosage than nonsmokers. Fish in the diet
supplies Omega-3 fatty acids, which are associated
with a reduced risk of chronic obstructive pulmonary
disease (emphysema or chronic bronchitis) in smokers.
Omega-3 fats also provide cardiovascular benefits as
well as an anti-depressive effect. Vitamin therapy
doesn’t reduce craving but it can help beat some of
the damage created by smoking. Vitamin B12 and folic
acid may help protect against smoking-induced cancer.

Epinephrine—A nervous system hormone stimulated by the nicotine in tobacco. It increases heart
rate and may raise smokers’ blood pressure.
Flavonoid—A food chemical that helps to limit
oxidative damage to the body’s cells, and protects
against heart disease and cancer.
Free radical—An unstable molecule that causes
oxidative damage by stealing electrons from surrounding molecules, thereby disrupting activity in
the body’s cells.
Nicotine—The addictive ingredient of tobacco, it
acts on the nervous system and is both stimulating
and calming.

Prevention
How do you give up your cigarettes for good and
never go back to them again?

Nicotine replacement therapy—A method of
weaning a smoker away from both nicotine and
the oral fixation that accompanies a smoking
habit by giving the smoker smaller and smaller
doses of nicotine in the form of a patch or gum.

Here are a few tips from the experts:


Have a plan and set a definite quit date.



Get rid of all the cigarettes and ashtrays at home or in
your desk at work.



Don’t allow others to smoke in your house.



Tell your friends and neighbors that you’re quitting.
Doing so helps make quitting a matter of pride.



Chew sugarless gum or eat sugar-free hard candy to
redirect the oral fixation that comes with smoking.
This will prevent weight gain, too.



Eat as much as you want, but only low-calorie foods
and drinks. Drink plenty of water. This may help
with the feelings of tension and restlessness that quitting can bring. After eight weeks, you’ll lose your
craving for tobacco, so it’s safe then to return to your
usual eating habits.

GALE ENCYCLOPEDIA OF MEDICINE

Sidestream smoke—The smoke that is emitted
from the burning end of a cigarette or cigar, or
that comes from the end of a pipe. Along with
exhaled smoke, it is a constituent of second-hand
smoke.



Stay away from social situations that prompt you to
smoke. Dine in the nonsmoking section of
restaurants.



Spend the money you save not smoking on an occasional treat for yourself.
3473

Smoking

Acupuncture

Snoring

Resources
PERIODICALS

‘‘AAAAI, EPA Mount Effort to Raise Awareness to
Dangers of Secondhand Smoke.’’ Immunotherapy
Weekly November 30, 2001: 30.
Batra, V., A. A. Patkar, W. H. Berrettini, et al. ‘‘The Genetic
Determinants of Smoking.’’ Chest 123 (May 2003):
1338–1340.
Ferry, L., and J. A. Johnston. ‘‘Efficacy and Safety of
Bupropion SR for Smoking Cessation: Data from
Clinical Trials and Five Years of Postmarketing
Experience.’’ International Journal of Clinical Practice
57 (April 2003): 224–230.
Janson, Christer, Susan Chinn, Deborah Jarvis, et al. ‘‘Effect
of Passive Smoking on Respiratory Symptoms,
Bronchial Responsiveness, Lung Function, and Total
Serum IgE in the European Community Respiratory
Health Survey: A Cross-Sectional Study.’’ Lancet 358
(December 22, 2001): 2103.
Lerman, C., and W. Berrettini. ‘‘Elucidating the Role of
Genetic Factors in Smoking Behavior and Nicotine
Dependence.’’ American Journal of Medical Genetics
118-B (April 1, 2003): 48–54.
Maisonneuve, I. M., and S. D. Glick. ‘‘Anti-Addictive
Actions of an Iboga Alkaloid Congener: A Novel
Mechanism for a Novel Treatment.’’ Pharmacology,
Biochemistry, and Behavior 75 (June 2003): 607–618.
Richmomd, R., and N. Zwar. ‘‘Review of Bupropion for
Smoking Cessation.’’ Drug and Alcohol Review 22 (June
2003): 203–220.
Sellers, E. M., R. F. Tyndale, and L. C. Fernandes.
‘‘Decreasing Smoking Behaviour and Risk through
CYP2A6 Inhibition.’’ Drug Discovery Today 8 (June 1,
2003): 487–493.
‘‘Study Shows Link Between Asthma and Childhood
Exposure to Smoking.’’ Immunotherapy Weekly
October 10, 2001: np.
Yochum, L., L. H. Kushi, and A. R. Folsom. ‘‘Dietary
Flavonoid Intake and Risk of Cardiovascular Disease
in Postmenopausal Women.’’ American Journal of
Epidemiology 149, no. 10 (May 1999): 943–9.
ORGANIZATIONS

American Association of Oriental Medicine. 5530 Wisconsin
Avenue, Suite 1210, Chevy Chase, MD 20815. (301)
941-1064 or (888) 500-7999. <http://www.aaom.org>.
American Cancer Society. Contact the local organization or
call (800) 227-2345. <http://www.cancer.org>.
American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872 or (212) 315-8700. <http://
www.lungusa.org>.
Herb Research Foundation. 1007 Pearl St., Suite 200,
Boulder CO 80302. (303) 449-2265. <http://
www.herbs.org>.
National Heart, Lung, and Blood Institute (NHLBI).
Building 31, Room 5A52, 31 Center Drive, MSC 2486,
Bethesda, MD 20892. (301) 592-8573. <http://
www.nhlbi.nih.gov>.
3474

Smoking, Tobacco, and Health Information Line. Centers
for Disease Control and Prevention. Mailstop K-50,
4770 Buford Highway NE, Atlanta, GA 30341-3724.
(800) 232-1311. <http://www.cdc.gov/tobacco>.
OTHER

Virtual Office of the Surgeon General: Tobacco Cessation
Guideline. <http://www.surgeongeneral.gov/
tobacco>.

Barbara Boughton

Snoring
Definition
Snoring is a sound generated during sleep by
vibration of loose tissue in the upper airway.

Description
Snoring is one symptom of a group of disorders
known as sleep disordered breathing. It occurs when
the soft palate, uvula, tongue, tonsils, and/or muscles in
the back of the throat rub against each other and generate a vibrating sound during sleep. Twenty percent of
all adults are chronic snorers, and 45% of normal
adults snore occasionally. As people grow older, their
chance of snoring increases. Approximately half of all
individuals over 60 snore regularly.
In some cases, snoring is a symptom of a more
serious disorder called obstructed sleep apnea (OSA).
OSA occurs when part of the airway is closed off
(usually at the back of the throat) while a person is
trying to inhale during sleep, and breathing stops for
more than 10 seconds before resuming again. These
breathless episodes can occur as many as several hundred times a night.
People with OSA almost always snore heavily,
because the same narrowing of the airway that causes
snoring can also cause OSA. Snoring may actually
attribute to OSA as well, because the vibration of the
throat tissues which occurs in snoring can cause the
tissue to swell.
Snoring is associated with physical problems as
well as social stress. People who do not suffer from
OSA may be diagnosed with socially unacceptable
snoring (SUS), which refers to snoring that is loud
enough to prevent the sleeper’s bed partner or roommate from sleeping. SUS is a factor in the breakup of
some marriages and other long-term relationships.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
There are several major causes of snoring,
including:


Excessively relaxed throat muscles. Alcohol, drugs,
and sedatives can cause the throat muscles to become
lax, and/or the tongue to pull back into the airway.



Large uvula. The piece of tissue that hangs from the
back of the throat is called the uvula. Individuals
with a large or longer than average uvula can suffer
from snoring when the uvula vibrates in the airway.



Large tonsils and/or adenoids. The tonsils (tissue at
the back of either side of the throat) can also vibrate
if they are larger than normal, as can the adenoids.



Excessive weight. Overweight people are more likely
to snore. This is frequently caused by the extra throat
and neck tissue they are carrying around.



Nasal congestion. Colds and allergies can plug the
nose, creating a vacuum in the throat that results in
snoring as airflow increases.



Cysts and tumors. Cysts and/or tumors of the throat
can trigger snoring.



Structural problems of the nose. A deviated septum or
other nasal problems can also cause snoring.

In some cases the patient may be referred to a
dentist or orthodontist for evaluation of the jaw structure and dentition.
In addition, the patient may be examined by sleep
endoscopy. In this procedure, the patient is given a
medication (midazolam) to induce sleep. His or her
throat and nasal passages are then examined with a
flexible laryngoscope. In many cases, sleep endoscopy
reveals obstructions that are not apparent during a
standard physical examination of the throat. Many
patients are found to have obstructions at more than
one level in their breathing passages.

Treatment
Several surgical procedures are available for treating chronic snoring. These include:


Uvulopalathopharyngoplasty (UPPP), a surgical
procedure which involves removing excess throat
tissues (e.g., tonsils, parts of the soft palate) to
expand the airway.



Laser-assisted uvulopalatoplasty (LAUP) uses a surgical laser to remove part of the uvula and palate.



Palatal stiffening is a minimally-invasive surgical
technique where a laser or a cauterizer is used to
produce scar tissue in the soft palate in order to
stop the vibrations that produce snoring.



Radiofrequency ablation is another technique which
uses scarring to shrink the uvula and/or soft palate.
A needle electrode is used to shrink and scar the
mouth and throat tissues.

Diagnosis
A patient interview, and possibly an interview
with the patient’s spouse or anyone else in the household who has witnessed the snoring, is usually enough
for a diagnosis of snoring. A medical history that
includes questions about alcohol or tranquilizer use;
past ear, nose, and throat problems; and the pattern
and degree of snoring will be completed, and a physical exam will be performed to determine the cause of
the problem. This will typically include examination of
the throat to look for narrowing, obstruction, or malformations. If the snoring is suspected to be a symptom of a more serious disorder such as obstructive
sleep apnea, the patient will require further testing.
This testing is called a polysomnography study, and is
conducted during an overnight stay in a specialized
sleep laboratory. The polysomnography study include
measurements of heart rate, airflow at the mouth and
nose, respiratory effort, sleep stage (light sleep, deep
sleep, dream sleep, etc.), and oxygen level in the blood.
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
There are a number of remedies for snoring, but
few are proven clinically effective. Popular treatments
include:


Mechanical devices. Many splints, braces, and
other devices are available which reposition the
nose, jaw, and/or mouth in order to clear the airways. Other devices are designed to wake an individual when snoring occurs. Patients should consult a
dentist or orthodontist about these devices, as most
require custom fitting. In addition, persons with
certain types of gum disease or dental problems
should not be fitted with oral appliances to stop
snoring.



Nasal strips. Nasal strips that attach like an adhesive
bandage to the bridge of the nose are available at
most drugstores, and can help stop snoring in some
individuals by opening the nasal passages.
3475

Snoring

Moreover, a study published in 2002 indicates that
people who snore are at increased risk of developing
type 2 diabetes. Snoring appears to be a risk factor
that is independent of body weight or a family history
of diabetes.

Snoring











Continuous positive airway pressure (CPAP). Some
chronic snorers find relief by sleeping with a nasal
mask which provides air pressure to the throat.
Decongestants. Snoring caused by nasal congestion
may be successfully treated with decongestants.
Some effective herbal remedies that clear the nasal
passages include golden rod (Solidago virgauria) and
golden seal (Hydrastis canadensis). Steam inhalation
of essential oils of eucalyptus blue gum (Eucalyptus
globulus) or peppermint (Mentha x piperata) can also
relieve congestion.
Weight loss. Snoring thought to be caused by excessive weight may be curtailed by a sensible weight loss
and exercise program.
Sleep position. Snoring usually worsens when an
individual sleeps on his or her back, so sleeping on
one’s side may alleviate the problem. Those who
have difficulty staying in a side sleeping position
may find sleeping with pillows behind them helps
them maintain the position longer. Other devices
include a new vest designed to prevent the sleeper
from lying on his or her back.
Bed adjustments. For some people, raising the head
of the bed solves their snoring problem. A slight
incline can prevent the tongue from retracting into
the back of the throat. Bricks, wooden blocks, or
specially designed wedges can be used to elevate the
head of the bed approximately 4–l6 in (10–41 cm).

Alternative treatments that have been reported to
be effective for patients whose snoring is caused by
colds or allergies include acupuncture, homeopathy,
and aromatherapy treatments. Aromatherapy treatments for snoring typically make use of marjoram
oil, which is thought to be particularly effective in
clearing the nasal passages.

Prevention
Adults with a history of snoring may be able to
prevent snoring episodes with the following measures:


avoid alcohol and sedatives before bedtime



remove allergens from the bedroom



use a decongestant before bed



sleep on the side, not the back

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disorders of the Oral Region.’’ Section 9, Chapter 105
In The Merck Manual of Diagnosis and Therapy.
3476

KEY TERMS
Ablation—The removal of abnormal tissue growths
by surgery.
Cauterize—To seal tissue or blood vessels using a
heat or electrical source.
Continuous positive airway pressure (CPAP)—A
ventilation device that blows a gentle stream of air
into the nose during sleep to keep the airway open.
Deviated septum—A hole or perforation in the
septum, the wall that divides the two nasal cavities.
Endoscope—A slender optical instrument that
allows a doctor to examine the inside of the throat
or other hollow organ. Sleep endoscopy is a technique that allows the doctor to detect previously
unsuspected obstructions in the patient’s nose and
throat.
Obstructive sleep apnea (OSA)—A potentially lifethreatening condition characterized by episodes of
breathing cessation during sleep alternating with
snoring or disordered breathing. The low levels of
oxygen in the blood of patients with OSA may
eventually cause heart problems or stroke.
Polysomnography—A technique for diagnosing
sleep disorders with the use of a machine that
records the pulse, breathing rate and other variables while the patient sleeps.
Soft palate—The structure at the roof of the mouth
that separates the mouth and the pharynx.

Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Sleep Disorders.’’ Section 14, Chapter 173 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I, Chapter 5, ‘‘Acupuncture,’’ and Chapter 8,
‘‘Homeopathy.’’ New York: Simon & Schuster, 2002.
PERIODICALS

Al-Delaimy, W. K., J. E. Manson, W. C. Willett, et al.
‘‘Snoring as a Risk Factor for Type II Diabetes
Mellitus: A Prospective Study.’’ American Journal of
Epidemiology 155 (March 1, 2002): 394-395.
Ayappa, I., and D. M. Rapoport. ‘‘The Upper Airway in
Sleep: Physiology of the Pharynx.’’ Sleep Medicine
Reviews 7 (February 2003): 3–7.
Blumen, M. B., S. Dahan, I. Wagner, et al. ‘‘Radiofrequency
Versus LAUP for the Treatment of Snoring.’’
Otolaryngology and Head and Neck Surgery 126
(January 2002): 67-73.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Academy of Otolaryngology, Head and Neck
Surgery, Inc. One Prince Street, Alexandria, VA 223143357. (703) 836-4444. <http://www.entnet.org>.
American Academy of Sleep Medicine (AASM). One
Westbrook Corporate Center, Suite 920, Westchester,
IL 60154. (708) 492-0930. <http://
www.aasmnet.org>.
American Dental Association. 211 East Chicago Avenue,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.
American Sleep Apnea Association. Wake-Up Call: The
Wellness Letter for Snoring and Apnea. 1424 K Street
NW, Suite 302, Washington, DC 20005. (202) 293-3650.
<http://www.sleepapnea.org>.
National Sleep Foundation. 1522 K Street, NW, Suite 500,
Washington, DC 20005. <http://
www.sleepfoundation.org>.
OTHER

American Sleep Apnea Association (ASAA). Considering
Surgery for Snoring? <http://www.sleepapnea.org/
snoring.html>.
National Heart, Lung, and Blood Institute (NHLBI). Facts
About Sleep Apnea. NIH Publication No. 95-3798.
GALE ENCYCLOPEDIA OF MEDICINE

[cited April 13, 2003]. <http://www.nhlbi.nih.gov/
health/public/sleep/sleepapn.htm>.

Paula Anne Ford-Martin
Rebecca J. Frey, PhD

Sodium imbalance see Hypernatremia;
Hyponatremia
Somatization disorder see Somatoform
disorders

Somatoform disorders
Definition
The somatoform disorders are a group of mental
disturbances placed in a common category on the
basis of their external symptoms. These disorders are
characterized by physical complaints that appear to be
medical in origin but that cannot be explained in terms
of a physical disease, the results of substance abuse,
or by another mental disorder. In order to meet the
criteria for a somatoform disorder, the physical symptoms must be serious enough to interfere with the
patient’s employment or relationships, and must be
symptoms that are not under the patient’s voluntary
control.
It is helpful to understand that the present classification of these disorders reflects recent historical
changes in the practice of medicine and psychiatry.
When psychiatry first became a separate branch of
medicine at the end of the nineteenth century, the
term hysteria was commonly used to describe mental
disorders characterized by altered states of consciousness (for example, sleepwalking or trance states) or
physical symptoms (for example, a ‘‘paralyzed’’ arm
or leg with no neurologic cause) that could not be fully
explained by a medical disease. The term dissociation
was used for the psychological mechanism that allows
the mind to split off uncomfortable feelings, memories, or ideas so that they are lost to conscious recall.
Sigmund Freud and other pioneering psychoanalysts
thought that the hysterical patient’s symptoms
resulted from dissociated thoughts or memories reemerging through bodily functions or trance states.
Prior to the categorization all mental disorders that
were considered to be forms of hysteria were grouped
together on the basis of this theory about their cause.
Since 1980, however, the somatoform disorders and
the so-called dissociative disorders have been placed in
separate categories on the basis of their chief
3477

Somatoform disorders

Ellis, S. G., N. W. Craik, R. F. Deans, and C. D. Hanning.
‘‘Dental Appliances for Snoring and Obstructive Sleep
Apnoea: Construction Aspects for General Dental
Practitioners.’’ Dental Update 30 (January-February
2003): 16–22, 24–26.
Hassid, S., A. H. Afrapoli, C. Decaesteker, and G.
Choufani. ‘‘UPPP for Snoring: Long-Term Results and
Patient Satisfaction.’’ Acta Otorhinolaryngologica
Belgica 56 (2002): 157-162.
Hessel, N. S., and N. de Vries. ‘‘Diagnostic Work-Up of
Socially Unacceptable Snoring. II. Sleep Endoscopy.’’
European Archives of Otorhinolaryngology 259 (March
2002): 158-161.
Maurer, J. T., B. A. Stuck, G. Hein, et al. ‘‘Treatment
of Obstructive Sleep Apnea with a New Vest
Preventing the Supine Position.’’ [in German]
Deutsche medizinische Wochenschrift 128 (January
17, 2003): 71–75.
Nakano, H., T. Ikeda, M. Hayashi, et al. ‘‘Effects of Body
Position on Snoring in Apneic and Nonapneic
Snorers.’’ Sleep 26 (March 15, 2003): 169–172.
Remacle, M., E. Jouzdani, G. Lawson, and J. Jamart.
‘‘Laser-Assisted Surgery Addressing Snoring LongTerm Outcome Comparing CO2 Laser vs. CO2 Laser
Combined with Diode Laser.’’ Acta
Otorhinolaryngologica Belgica 56 (2002): 177-182.
Stevenson, J. E. ‘‘Diagnosis of Sleep Apnea.’’ Wisconsin
Medical Journal 102 (2003): 25–27, 46.
Trotter, M. I., A. R. D’Souza, and D. W. Morgan.
‘‘Medium-Term Outcome of Palatal Surgery for
Snoring Using the Somnus Unit.’’ Journal of
Laryngology and Otology 116 (February 2002): 116-118.

Somatoform disorders

symptoms. In general, the somatoform disorders are
characterized by disturbances in the patient’s physical
sensations or ability to move the limbs or walk, while
the dissociative disorders are marked by disturbances
in the patient’s sense of identity or memory.

Description
As a group, the somatoform disorders are difficult
to recognize and treat because patients often have long
histories of medical or surgical treatment with several
different doctors. In addition, the physical symptoms
are not under the patient’s conscious control, so that
he or she is not intentionally trying to confuse the
doctor or complicate the process of diagnosis.
Somatoform disorders are, however, a significant problem for the health care system because patients with
these disturbances overuse medical services and
resources.
Somatization disorder (Briquet’s syndrome)
Somatization disorder was formerly called
Briquet’s syndrome, after the French physician who
first recognized it. The distinguishing characteristic of
this disorder is a group or pattern of symptoms in
several different organ systems of the patient’s body
that cannot be accounted for by medical illness. The
criteria for this disorder require four symptoms of
pain, two symptoms in the digestive tract, one symptom involving the sexual organs, and one symptom
related to the nervous system. Somatization disorder
usually begins before the age of 30. It is estimated that
0.2% of the United States population will develop this
disorder in the course of their lives. Another
researcher estimates that 1% of all women in the
United States have symptoms of this disorder. The
female-to-male ratio is estimated to range between
5:1 and 20:1.
Somatization disorder is considered to be a
chronic disturbance that tends to persist throughout
the patient’s life. It is also likely to run in families.
Some psychiatrists think that the high female-to-male
ratio in this disorder reflects the cultural pressures
on women in North American society and the social
‘‘permission’’ given to women to be physically weak or
sickly.
Conversion disorder
Conversion disorder is a condition in which the
patient’s senses or ability to walk or move are
impaired without a recognized medical or neurological disease or cause and in which psychological factors
3478

(such as stress or trauma) are judged to be temporarily
related to onset or exacerbation. The disorder gets its
name from the notion that the patient is converting a
psychological conflict or problem into an inability to
move specific parts of the body or to use the senses
normally. An example of a conversion reaction would
be a patient who loses his or her voice in a situation in
which he or she is afraid to speak. The symptom
simultaneously contains the anxiety and serves to get
the patient out of the threatening situation. The resolution of the emotion that underlies the physical symptom is called the patient’s primary gain, and the change
in the patient’s social, occupational, or family situation that results from the symptom is called a secondary gain. Doctors sometimes use these terms when they
discuss the aftereffects of conversion disorder or of
other somatoform disorders on the patient’s emotional adjustment and lifestyle.
The specific physical symptoms of conversion disorder may include a loss of balance or paralysis of an
arm or leg; the inability to swallow or speak; the loss of
touch or pain sensation; going blind or deaf; seeing
double; or having hallucinations, seizures, or
convulsions.
Unlike somatization disorder, conversion disorder may begin at any age, and it does not appear to
run in families. It is estimated that as many as 34% of
the population experiences conversion symptoms over
a lifetime, but that the disorder is more likely to occur
among less educated or sophisticated people.
Conversion disorder is not usually a chronic disturbance; 90% of patients recover within a month, and
most do not have recurrences. The female-to-male
ratio is between 2:1 and 5:1. Male patients are likely
to develop conversion disorders in occupational settings or military service.
Pain disorder
Pain disorder is marked by the presence of severe
pain as the focus of the patient’s concern. This category of somatoform disorder covers a range of
patients with a variety of ailments, including chronic
headaches, back problems, arthritis, muscle aches and
cramps, or pelvic pain. In some cases the patient’s pain
appears to be largely due to psychological factors, but
in other cases the pain is derived from a medical condition as well as the patient’s psychology.
Pain disorder is relatively common in the general
population, partly because of the frequency of workrelated injuries in the United States. This disorder
appears to be more common in older adults, and the sex
ratio is nearly equal, with a female-to-male ratio of 2:1.
GALE ENCYCLOPEDIA OF MEDICINE

Hypochondriasis is a somatoform disorder
marked by excessive fear of or preoccupation with
having a serious illness that persists in spite of medical
testing and reassurance. It was formerly called hypochondriacal neurosis.
Although hypochondriasis is usually considered a
disorder of young adults, it is now increasingly recognized in children and adolescents. It may also develop
in elderly people without previous histories of healthrelated fears. The disorder accounts for about 5% of
psychiatric patients, and is equally common in men
and women. Hypochondriasis may persist over a number of years but usually occurs as a series of episodes
rather than continuous treatment-seeking. The flareups of the disorder are often correlated with stressful
events in the patient’s life.

the increased influence of media preoccupation with
physical perfection.

Causes and symptoms
Because groups the somatoform disorders are
categorized on the basis of symptom patterns, their
causes as presently understood include several different factors.
Family stress
Family stress is believed to be one of the most
common causes of somatoform disorders in children
and adolescents. Conversion disorders in this age
group may also be connected with physical or sexual
abuse within the family of origin.
Parental modeling

Body dysmorphic disorder
Body dysmorphic disorder is a new category of
somatoform disorders. It is defined as a preoccupation
with an imagined or exaggerated defect in appearance.
Most cases involve features on the patient’s face or
head, but other body parts–especially those associated
with sexual attractiveness, such as the breasts or genitals–may also be the focus of concern.
Body dysmorphic disorder is regarded as a
chronic condition that usually begins in the patient’s
late teens and fluctuates over the course of time. It was
initially considered to be a relatively unusual disorder,
but may be more common than was formerly thought.
It appears to affect men and women with equal frequency. Patients with body dysmorphic disorder frequently have histories of seeking or obtaining plastic
surgery or other procedures to repair or treat the
supposed defect. Some may even meet the criteria for
a delusional disorder of the somatic type.

Somatization disorder and hypochondriasis may
result in part from the patient’s unconscious reflection
or imitation of parental behaviors. This ‘‘copycat’’
behavior is particularly likely if the patient’s parent
derived considerable secondary gain from his or her
symptoms.
Cultural influences
Cultural influences appear to affect the gender
ratios and body locations of somatoform disorders,
as well as their frequency in a specific population.
Some cultures (for example, Greek and Puerto
Rican) report higher rates of somatization disorder
among men than is the case for the United States. In
addition, researchers found lower levels of somatization disorder among people with higher levels of education. People in Asia and Africa are more likely to
report certain types of physical sensations (for example, burning hands or feet, or the feeling of ants crawling under the skin) than are Westerners.

Somatoform disorders in children and adolescents
The most common somatoform disorders in children and adolescents are conversion disorders,
although body dysmorphic disorders are being
reported more frequently. Conversion reactions in
this age group usually reflect stress in the family or
problems with school rather than long-term psychiatric disturbances. Some psychiatrists speculate that
adolescents with conversion disorders frequently
have overprotective or overinvolved parents with a
subconscious need to see their child as sick; in many
cases the son or daughter’s symptoms become the
center of family attention. The rise in body dysmorphic disorders in adolescents is thought to reflect
GALE ENCYCLOPEDIA OF MEDICINE

Biological factors
Genetic or biological factors may also play a role.
For example, people who suffer from somatization
disorder may also differ in how they perceive and
process pain.

Diagnosis
Accurate diagnosis of somatoform disorders is
important to prevent unnecessary surgery, laboratory
tests, or other treatments or procedures. Because
somatoform disorders are associated with physical
symptoms, patients are often diagnosed by primary
3479

Somatoform disorders

Hypochondriasis

Somatoform disorders

care physicians as well as by psychiatrists. In many
cases the diagnosis is made in a general medical clinic.
Children and adolescents with somatoform disorders
are most likely to be diagnosed by pediatricians.
Diagnosis of somatoform disorders requires a thorough physical workup to exclude medical and neurological conditions, or to assess their severity in patients
with pain disorder. A detailed examination is especially necessary when conversion disorder is a possible
diagnosis, because some neurological conditions–
including multiple sclerosis and myasthenia gravis–
have on occasion been misdiagnosed as conversion
disorder. Some patients who receive a diagnosis of
somatoform disorder ultimately go on to develop neurologic disorders.
In addition to ruling out medical causes for the
patient’s symptoms, a doctor who is evaluating a
patient for a somatization disorder will consider the
possibility of other psychiatric diagnoses or of overlapping psychiatric disorders. Somatoform disorders
often coexist with personality disorders because of the
chicken-and-egg relationship between physical illness
and certain types of character structure or personality traits. At one time, the influence of Freud’s theory
of hysteria led doctors to assume that the patient’s
hidden emotional needs ‘‘cause’’ the illness. But in
many instances, the patient’s personality may have
changed over time due to the stresses of adjusting to a
chronic disease. This gradual transformation is particularly likely in patients with pain disorder. Patients
with somatization disorder often develop panic
attacks or agoraphobia together with their physical
symptoms. In addition to anxiety or personality
disorders, the doctor will usually consider major
depression as a possible diagnosis when evaluating a
patient with symptoms of a somatoform disorder.
Pain disorders may be associated with depression,
and body dismorphic disorder may be associated
with obsessive-compulsive disease.

Medications
Patients with somatoform disorders are sometimes given antianxiety drugs or antidepressant drugs
if they have been diagnosed with a coexisting mood or
anxiety disorder. In general, however, it is considered
better practice to avoid prescribing medications for
these patients since they are likely to become psychologically dependent on them. However, body dysmorphic disorder as been successfully treated with
selective serotonin reuptake inhibitors (SSRI)
antidepressants.
Psychotherapy
Patients with somatoform disorders are not considered good candidates for psychoanalysis and other
forms of insight-oriented psychotherapy. They can
benefit, however, from supportive approaches to
treatment that are aimed at symptom reduction and
stabilization of the patient’s personality. Some
patients with pain disorder benefit from group therapy
or support groups, particularly if their social network
has been limited by their pain symptoms. Cognitivebehavioral therapy is also used sometimes to treat pain
disorder.
Family therapy is usually recommended for children or adolescents with somatoform disorders, particularly if the parents seem to be using the child as a
focus to divert attention from other difficulties.
Working with families of chronic pain patients also
helps avoid reinforcing dependency within the family
setting.
Hypnosis is a technique that is sometimes used as
part of a general psychotherapeutic approach to conversion disorder because it may allow patients to
recover memories or thoughts connected with the
onset of the physical symptoms.

Alternative treatment
Treatment
Relationship with primary care practitioner
Because patients with somatoform disorders often
have lengthy medical histories, a long-term relationship with a trusted primary care practitioner (PCP) is a
safeguard against unnecessary treatments as well as a
comfort to the patient. Many PCPs prefer to schedule
brief appointments on a regular basis with the patient
and keep referrals to specialists to a minimum. This
practice also allows them to monitor the patient for
any new physical symptoms or diseases. However,
some PCPs work with a psychiatric consultant.
3480

Patients with somatization disorder or pain disorder may be helped by a variety of alternative therapies including acupuncture, hydrotherapy, therapeutic
massage, meditation, botanical medicine, and homeopathic treatment. Relief of symptoms, including pain,
can occur on the physical level, as well as on the
mental, emotional, and spiritual levels.

Prognosis
The prognosis for somatoform disorders depends,
as a rule, on the patient’s age and whether the disorder
is chronic or episodic. In general, somatization
GALE ENCYCLOPEDIA OF MEDICINE

Briquet’s syndrome—Another name for somatization disorder.
Conversion disorder—A somatoform disorder
characterized by the transformation of a psychological feeling or impulse into a physical symptom.
Conversion disorder was previously called hysterical neurosis, conversion type.
Dissociation—A psychological mechanism in
which the mind splits off certain aspects of a traumatic event from conscious awareness.
Dissociation can affect the patient’s memory,
sense of reality, and sense of identity.
Hysteria—The earliest term for a psychoneurotic
disturbance marked by emotional outbursts and/or
disturbances of movement and sense perception.
Some forms of hysteria are now classified as somatoform disorders and others are grouped with the
dissociative disorders.
Hysterical neurosis—An older term for conversion
disorder or dissociative disorder.
Primary gain—The immediate relief from guilt,
anxiety, or other unpleasant feelings that a patient
derives from a symptom.
Repression—A
unconscious
psychological
mechanism in which painful or unacceptable
ideas, memories, or feelings are removed from conscious awareness or recall.
Secondary gain—The social, occupational, or
interpersonal advantages that a patient derives
from symptoms. A patient’s being relieved of his
or her share of household chores by other family
members would be an example of secondary gain.
Somatoform disorder—A category of psychiatric
disorder characterized by physical complaints that
appear to be medical in origin but that cannot be
explained in terms of a physical disease, the results
of substance abuse, or by another mental disorder.

disorder and body dysmorphic disorder rarely resolve
completely. Hypochondriasis and pain disorder may
resolve if there are significant improvements in the
patient’s overall health and life circumstances, and
people with both disorders may go through periods
when symptoms become less severe (remissions) or
become worse (exacerbations). Conversion disorder
tends to be rapidly resolved, but may recur in about
25% of all cases.
GALE ENCYCLOPEDIA OF MEDICINE

Generalizations regarding prevention of somatoform disorders are difficult because these syndromes
affect different age groups, vary in their symptom
patterns and persistence, and result from different
problems of adjustment to the surrounding culture.
In theory, allowing expression of emotional pain in
children, rather than regarding it as ‘‘weak,’’ might
reduce the secondary gain of physical symptoms that
draw the care or attention of parents.
Resources
BOOKS

Eisendrath, Stuart J. ‘‘Psychiatric Disorders.’’ In Current
Medical Diagnosis and Treatment, 1998, edited by
Stephen McPhee, et al., 37th ed. Stamford: Appleton &
Lange, 1997.

Rebecca J. Frey, PhD

Somatotrophic hormone test see Growth
hormone tests

Sore throat
Definition
Sore throat, also called pharyngitis, is a painful
inflammation of the mucous membranes lining the
pharynx. It is a symptom of many conditions, but
most often is associated with colds or influenza. Sore
throat may be caused by either viral or bacterial infections or environmental conditions. Most sore throats
heal without complications, but they should not be
ignored because some develop into serious illnesses.

Description
Almost everyone gets a sore throat at one time or
another, although children in child care or grade
school have them more often than adolescents and
adults. Sore throats are most common during the
winter months when upper respiratory infections
(colds) are more frequent.
Sore throats can be either acute or chronic. Acute
sore throats are the more common. They appear suddenly and last from three to about seven days. A
chronic sore throat lasts much longer and is a symptom of an unresolved underlying condition or disease,
such as a sinus infection.
3481

Sore throat

Prevention

KEY TERMS

Sore throat

Causes and symptoms
Sore throats have many different causes, and may
or may not be accompanied by cold symptoms, fever,
or swollen lymph glands. Proper treatment depends on
understanding the cause of the sore throat.
Viral sore throat
Viruses cause 90–95% of all sore throats. Cold
and flu viruses are the main culprits. These viruses
cause an inflammation in the throat and occasionally
the tonsils (tonsillitis). Cold symptoms almost always
accompany a viral sore throat. These can include a
runny nose, cough, congestion, hoarseness, conjunctivitis, and fever. The level of throat pain varies from
uncomfortable to excruciating, when it is painful for
the patient to eat, breathe, swallow, or speak.
Another group of viruses that cause sore throat
are the adenoviruses. These may also cause infections
of the lungs and ears. In addition to a sore throat,
symptoms that accompany an adenovirus infection
include cough, runny nose, white bumps on the tonsils
and throat, mild diarrhea, vomiting, and a rash. The
sore throat lasts about one week.
A third type of virus that can cause severe sore
throat is the coxsackie virus. It can cause a disease
called herpangina. Although anyone can get herpangina, it is most common in children up to age ten and is
more prevalent in the summer or early autumn.
Herpangina is sometimes called summer sore throat.
Three to six days after being exposed to the virus, an
infected person develops a sudden sore throat that is
accompanied by a substantial fever usually between
102–1048F (38.9–408C). Tiny grayish-white blisters
form on the throat and in the mouth. These fester and
become small ulcers. Throat pain is often severe, interfering with swallowing. Children may become dehydrated if they are reluctant to eat or drink because of
the pain. In addition, people with herpangina may vomit,
have abdominal pain, and generally feel ill and miserable.
One other common cause of a viral sore throat is
mononucleosis. Mononucleosis occurs when the
Epstein-Barr virus infects one specific type of lymphocyte. The infection spreads to the lymphatic system,
respiratory system, liver, spleen, and throat.
Symptoms appear 30–50 days after exposure.
Mononucleosis, sometimes called the kissing disease, is extremely common. It is estimated that by the
age of 35–40, 80–95% of Americans will have had
mononucleosis. Often, symptoms are mild, especially
in young children, and are diagnosed as a cold. Since
symptoms are more severe in adolescents and adults,
3482

more cases are diagnosed as monomucleosis in this age
group. One of the main symptoms of mononucleosis is
a severe sore throat.
Although a runny nose and cough are much more
likely to accompany a sore throat caused by a virus
than one caused by a bacteria, there is no absolute way
to tell what is causing the sore throat without a laboratory test. Viral sore throats are contagious and are
passed directly from person to person by coughing
and sneezing.
Bacterial sore throat
From 5–10% of sore throats are caused by bacteria. The most common bacterial sore throat results
from an infection by group A Streptococcus. This type
of infection is commonly called strep throat. Anyone
can get strep throat, but it is most common in school
age children.
Pharyngeal gonorrhea, a sexually transmitted bacterial disease, causes a severe sore throat. Gonorrhea
in the throat is transmitted by having oral sex with an
infected person.
Noninfectious sore throat
Not all sore throats are caused by infection.
Postnasal drip can irritate the throat and make it
sore. It can be caused by hay fever and other allergies
that irritate the sinuses. Environmental and other conditions, such as heavy smoking or breathing secondhand smoke, heavy alcohol consumption, breathing
polluted air or chemical fumes, or swallowing substances that burn or scratch the throat can also cause
pharyngitis. Dry air, like that in airplanes or from
forced hot air furnaces, can make the throat sore.
People who breathe through their mouths at night
because of nasal congestion often get sore throats
that improve as the day progresses. Sore throat caused
by environmental conditions is not contagious.

Diagnosis
It is easy for people to tell if they have a sore
throat, but difficult to know what has caused it without laboratory tests. Most sore throats are minor and
heal without any complications. A small number of
bacterial sore throats do develop into serious diseases.
Because of this, it is advisable to see a doctor if a sore
throat lasts more than a few days or is accompanied by
fever, nausea, or abdominal pain.
Diagnosis of a sore throat by a doctor begins with
a physical examination of the throat and chest. The
doctor will also look for signs of other illness, such as a
GALE ENCYCLOPEDIA OF MEDICINE

Because mononucleosis is caused by a virus, there
is no specific drug treatment available. Rest, a healthy
diet, plenty of fluids, limiting heavy exercise and competitive sports, and treatment of aches with acetaminophen (Datril, Tylenol, Panadol) or ibuprofen (Advil,
Nuprin, Motrin, Medipren) will help the illness pass.
Nearly 90% of mononucleosis infections are mild. The
infected person does not normally get the disease again.
In the case of chronic sore throat, it is necessary to
treat the underlying disease to heal the sore throat. If a
sore throat caused by environmental factors, the
aggravating stimulus should be eliminated from the
sufferer’s environment.
Home care for sore throat
This young woman is having her sore throat examined by a
medical practitioner using a fiber-optic tongue depressor.
(Custom Medical Stock Photo. Reproduced by permission.)

sinus infection or bronchitis. Since both bacterial and
viral sore throat are contagious and pass easily from
person to person, the doctor will seek information
about whether the patient has been around other people with flu, sore throat, colds, or strep throat. If it
appears that the patient may have strep throat, the
doctor will do laboratory tests.
If mononucleosis is suspected, the doctor may do
a mono spot test to look for antibodies indicating the
presence of the Epstein-Barr virus. The test in inexpensive, takes only a few minutes, and can be done in a
physician’s office. An inexpensive blood test can also
determine the presence of antibodies to the mononucleosis virus.

Regardless of the cause of a sore throat, there are
some home care steps that people can take to ease their
discomfort. These include:


taking acetaminophen or ibuprofen for pain; aspirin
should not be given to children because of its association with increased risk for Reye’s Syndrome, a
serious disease



gargling with warm double strength tea or warm salt
water made by adding 1 tsp of salt to 8 oz (237 ml) of
water



drinking plenty of fluids, but avoiding acid juices like
orange juice, which can irritate the throat (sucking
on popsicles is a good way to get fluids into children)



eating soft, nutritious foods like noodle soup and
avoiding spicy foods



refraining from smoking



resting until the fever is gone, then resuming strenuous activities gradually



a room humidifier may make sore throat sufferers
more comfortable



antiseptic lozenges and sprays may aggravate the
sore throat rather than improve it

Treatment
Effective treatment varies depending on the cause
of the sore throat. As frustrating as it may be to the
patient, viral sore throat is best left to run its course
without drug treatment. Antibiotics have no effect on a
viral sore throat. They do not shorten the length of the
illness, nor do they lessen the symptoms.
Sore throat caused by a streptococci or another
bacteria must be treated with antibiotics. Penicillin is
the preferred medication. Oral penicillin must be
taken for 10 days. Patients need to take the entire
amount of antibiotic prescribed, even after symptoms
of the sore throat improve. Stopping the antibiotic
GALE ENCYCLOPEDIA OF MEDICINE

Alternative treatment
Alternative treatment focuses on easing the symptoms of sore throat using herbs and botanical
medicines.


Aromatherapists recommend inhaling the fragrances
of essential oils of lavender (Lavandula officinalis),
3483

Sore throat

early can lead to a return of the sore throat.
Occasionally a single injection of long-acting penicillin
G is given instead of 10 days of oral treatment. These
medications generally cost under $15.

South American blastomycosis

thyme (Thymus vulgaris), eucalyptus (Eycalyptus globulus), sage (Salvia officinalis), and sandalwood.


Ayurvedic practitioners suggest gargling with a mixture of water, salt, and tumeric (Curcuma longa)
powder or astringents such as alum, sumac, sage,
and bayberry (Myrica spp.).



Herbalists recommend taking osha root (Ligusticum
porteri) internally for infection or drinking ginger
(Zingiber officinale) or slippery elm (Ulmus fulva)
tea for pain.



Homeopaths may treat sore throats with superdilute
solutions Lachesis, Belladonna, Phytolacca), yellow
jasmine (Gelsemium), or mercury.



Nutritional recommendations include zinc lozenges
every two hours along with vitamin C with bioflavonoids, vitamin A, and beta-carotene supplements.

KEY TERMS
Antigen—A foreign protein to which the body
reacts by making antibodies
Conjunctivitis—An inflammation of the membrane
surrounding the eye; also known as pinkeye.
Lymphocyte—A type of white blood cell.
Lymphocytes play an important role in fighting
disease.
Pharynx—The pharynx is the part of the throat that
lies between the mouth and the larynx or voice
box.
Toxin—A poison. In the case of scarlet fever, the
toxin is secreted as a byproduct of the growth of the
streptococcus bacteria and causes a rash.

Prognosis
Sore throat caused by a viral infection generally
clears up on its own within one week with no complications. The exception is mononucleosis. Ninety percent of cases of mononucleosis clear up without
medical intervention or complications, so long as
dehydration does not occur. In young children the
symptoms may last only a week, but in adolescents
the symptoms last longer. Adults over age 30 have the
most severe and long lasting symptoms. Adults may
take up to six months to recover. In all age groups
fatigue and weakness may continue for up to six weeks
after other symptoms disappear.
In rare cases of mononucleosis, breathing may be
obstructed because of swollen tonsils, adenoids, and
lymph glands. If this happens, the patient should
immediately seek emergency medical care.
Patients with bacterial sore throat begin feeling
better about 24 hours after starting antibiotics.
Untreated strep throat has the potential to cause scarlet fever, kidney damage, or rheumatic fever. Scarlet
fever causes a rash, and can cause high fever and
convulsions. Rheumatic fever causes inflammation of
the heart and damage to the heart valves. Taking
antibiotics within the first week of a strep infection
will prevent these complications. People with strep
throat remain contagious until after they have been
taking antibiotics for 24 hours.

Prevention
There is no way to prevent a sore throat; however,
the risk of getting one or passing one on to another
person can be minimized by:
3484



washing hands well and frequently



avoiding close contact with someone who has a sore
throat



not sharing food and eating utensils with anyone



not smoking



staying out of polluted air

Resources
BOOKS

Berktow, Robert, editor. The Merck Manual of Diagnosis
and Therapy. 16th ed. Rahway, NJ: Merck Research
Laboratories, 1992.

Tish Davidson, A.M.

Sotalol see Antiarrhythmic drugs
Sound therapy see Music therapy

South American blastomycosis
Definition
South American blastomycosis is a potentially
fatal, chronic fungus infection that occurs more often
in men. The infection may affect different parts of the
body, including the lungs or the skin, and may cause
ulcers of the mouth, voicebox, and nose.
GALE ENCYCLOPEDIA OF MEDICINE

B. Sulfonamide drugs have been used and can stop the
progress of the infection, but they don’t kill the
fungus.

Amphotericin B—A drug used to treat fungal
infections.
Sulfonamide drugs—A group of antibacterial drugs
used to treat infections of the lungs and skin, among
other things.

Scientists are studying new treatments for the
fungal infection, including ketoconazole, fluconazole,
and itraconazole, which appear to be equally effective
as amphotericin B, according to research.

Prognosis
Description
South American blastomycosis occurs primarily
in Brazil, although cases crop up in Mexico, Central
America, or other parts of South America. It affects
men between ages 20 and 50 about 10 times more often
than women.
The disease is far more serious than its North
American variant (North American blastomycosis),
which is endemic to the eastern United States, southern Canada, and the midwest.
South American blastomycosis is known medically as paracoccidioidal granuloma, or paracoccidioidomycosis. The infection has a very long incubation
period (at least five years).

The disease is chronic and often fatal. Because
blastomycosis may be recurrent, patients should continue follow-up care for several years.

Prevention
There is no way to prevent the disease.
Resources
ORGANIZATIONS

National Institute of Allergy and Infectious Disease.
Building 31, Room 7A-50, 31 Center Drive MSC 2520,
Bethesda, MD 20892-2520. (301) 496-5717. <http://
www.niaid.nih.gov/default.htm>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Causes and symptoms
South American blastomycosis is caused by the
yeast-like fungus Paracoccidioides brasiliensis that is
acquired by breathing in the spores of the fungus,
which is commonly found in old wood and soil. It
may appear very similar to tuberculosis; in fact, both
diseases may infect a patient at the same time.
Symptoms include ulcers in the mouth, larynx and
nose, in addition to large, draining lymph nodes,
cough, chest pain, swollen lymph glands, weight loss,
and lesions on the skin, genitals, and intestines. There
may also be lesions in the liver, spleen, intestines, and
adrenal glands.

Carol A. Turkington

Space medicine see Aviation medicine
Spanish flu see Influenza
Spastic colitis see Irritable bowel syndrome
Spastic colon see Irritable bowel syndrome

Speech disorders
Definition

Diagnosis
A physician can diagnose the condition by microscopic examination of a smear prepared from a lesion or
sputum (spit). Biopsy specimens may also reveal the
infection. While blood tests are helpful, they can’t determine the difference between past and active infection.

Treatment
The primary goal of treatment is to control the
infection. The best treatment has been amphotericin
GALE ENCYCLOPEDIA OF MEDICINE

According to the American Speech-LanguageHearing Association (ASHA), a language disorder is
an impairment in comprehension use of the spoken,
written, or other symbol system.

Description
Speech disorders affect the language and
mechanics, the content of speech, or the function of
language in communication. Because speech disorders
affect a person’s ability to communicate effectively,
3485

Speech disorders

KEY TERMS

Speech disorders

every aspect of the person’s life can be affected, for
example, the person’s ability to make friends, and to
communicate at school or at work.
Amyotrophic lateral sclerosis (ALS)
Amyotrophic lateral sclerosis (ALS), also known
as Lou Gehrig’s disease, is a neurological disease that
attacks the nerve cells in the brain that control voluntary muscles. ALS causes motor neurons to die so that
the brain and spinal cord are unable to send messages
to the muscles telling them to move. Because the muscles are not functioning, they begin to atrophy.
Muscles in the face and jaw can be affected, and
thereby affecting a person’s speech.
Aphasia
Aphasia results from damage to the language centers of the brain, which affects a person’s ability to
communicate through speaking, listening, and
writing.
Persons with aphasia have trouble with expressive
language, what is said, or receptive language, what is
understood. Not only are speech and understanding
speech affected, but also reading and writing is
affected. The severity of aphasia varies from person
to person, but in the most severe cases, a person may
not be able to understand speech at all. Persons with
mild aphasia may only become confused when speech
becomes lengthy and complicated.
Developmental apraxia of speech
Developmental apraxia is a disorder that affects
the nervous system and affects a person’s ability to
sequence and say sounds, syllables, and words. The
brain does not send the correct messages to the mouth
and jaw so that the person can say what he or she
wants to say.
Children who are suffering from this disorder
don’t babble as an infant and first words are delayed.
Older children may have more difficulty with longer
phrases, and may appear to be searching for words to
express a thought. Listeners will likely have a difficult
time understanding the child.
Laryngeal cancer
Laryngeal cancer is characterized by a malignant
growth in the larynx, or the voice box, which sometimes requires removal of the larynx or part of it.
Cancer anywhere in the throat affects speech,
swallowing, and chewing. Depending on the size of
the growth, a person may have trouble moving the
3486

mouth and lips. Therefore, speech sounds and eating
will be affected and a person will have trouble
communicating.
Orofacial myofunctional disorders
Orofacial myofunctional disorder (OMD) causes
the tongue to move forward in an exaggerated manner
while a person is speaking or swallowing. The tongue
also may protrude when resting in the mouth.
Because heredity contributes to the size and shape
of a person’s mouth, there may be genetic reasons for
the disorder. Allergies also affect the mouth and face
muscles, which make it difficult to breathe because of
nasal congestion. Because a person may sleep with the
tongue protruding, lip muscles weaken. Enlarged tonsils also can block airways, creating the same breathing problems. Additionally, thumb-sucking, nailbiting, and teeth-clenching and grinding also can contribute to the disorder.
Stuttering
Stuttering is a disorder of speech fluency that frequently interrupts the flow of speech.
Because children typically stumble and confuse
their words as speech develops, stuttering is not immediately evident. It is usually when children become
older and continue to stumble that stuttering becomes
evident.

Causes and symptoms
Amyotrophic lateral sclerosis (ALS)
Initial symptoms include weakness in any part of
the body, and appendages begin to tire easily.
Occasionally the disease affects only one appendage
rather than both at the same time. Persons with ALS
may have trouble maintaining balance and may stumble or have difficulty with tasks that require manual
dexterity, such as buttoning a shirt or tying a shoe.
Eventually, the diaphragm and chest wall become
so weak that a person cannot breathe on his or her
own and needs the help of a ventilator. Because of the
lack of muscle strength, a person with ALS will experience difficulty speaking loudly and clearly until the
person is unable to speak at all using the vocal cords.
The person will have difficulty pronouncing words
and have difficulty completing lengthy sentences.
Along with the difficulty in speaking also comes
difficulty in chewing and swallowing. Food can be
broken down and pureed to make it easier to chew
and swallow. However, a person eventually will have
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Aphasia
Stroke is the most common cause of aphasia,
although other injuries, such as a brain tumor or gunshot wound, also can cause aphasia.

Diagnosis
Amyotrophic lateral sclerosis (ALS)
About 20,000 people in the United States have
ALS at any given time with 5,000 new cases diagnosed
every year. ALS is in the same family of disorders as
multiple sclerosis, Parkinson’s disease, and muscular
dystrophy. Persons of all races and ethic groups are
afflicted by the disease, although men are more likely
to have it than women.
Aphasia

Developmental apraxia of speech
Developmental apraxia is a disorder that affects
the nervous system and affects a person’s ability to
sequence and say sounds, syllables, and words. The
brain does not send the correct messages to the mouth
and jaw so that the person can say what he or she
wants to say.
Children who are suffering from this disorder
don’t babble as an infant and first words are delayed.
Older children may have more difficulty with longer
phrases, and may appear to be searching for words to
express a thought. Listeners will likely have a difficult
time understanding the child.
There is no known cause for developmental
apraxia of speech. Symptoms include weakness of
the jaw, tongue, and lips, and delayed speech development. Persons with the disorder also may have trouble
identifying an object in the mouth using the sense of
touch, which is known as oral-sensory perception.
Laryngeal cancer
Any kind of smoking of cigarettes, cigars, or
tobacco and alcohol abuse contribute to oral cancer,
including smokeless tobacco. Persons with laryngeal
cancer or another type of oral cancer may have a red
or white patch or lump in the mouth. Symptoms also
include difficulty chewing, swallowing, or chewing.
Stuttering
There is no known cause for stuttering, although
poor muscle coordination and the rate of language
development are believed to contribute to it.
Stuttering is characterized by repetition of
sounds, syllables, portions of a word, words, and complete phrases; stretching the sounds and syllables; hesitation between words; words spoken in spurts; tense
muscles in the jaw and mouth; and a feeling of loss of
control.
GALE ENCYCLOPEDIA OF MEDICINE

About 700,000 persons in the United States have
strokes every year, and one million are estimated to
have aphasia.
Developmental apraxia of speech
A child suspected to have apraxia should first
have his or her hearing tested to determine if the
child has any deafness. Muscle development in the
face and jaw should be evaluated and speech exercises
tested. Articulation of words should be tested as well
as the person’s expressive and receptive language
skills.
Laryngeal cancer
It is likely that a dentist or physician will first
detect signs of possible cancer. Oral cancer makes up
about 2–5% of all cancers, and about 30,000 cases are
diagnosed each year. Twice as many men than women
are diagnosed with cancer typically between the ages
of 50 and 70.
Orofacial myofunctional disorders
The diagnosis of orofacial myofunctional disorder affects speech sounds because of weak tongue tip
muscles, although a person’s speech may not be
affected at all.
Stuttering
Stuttering is a problem that most likely will manifest itself during childhood rather than adulthood.

Treatment
Amyotrophic lateral sclerosis (ALS)
In addition to treatments such as a feeding tube, a
person with ALS would likely enlist the help of a
speech therapist to help him or her determine ways in
which he or she can maintain vocal control. A person
also may enlist the help of an occupational therapist, a
3487

Speech disorders

difficulty chewing and swallowing foods that are broken down or pureed. When ability to eat is affected,
proper nutrition and body weight also are affected, and
medical professionals may decide that it is best to put
in a feeding tube.

Speech disorders

Alternative treatment

medical professional trained to help persons who have
trouble with activities of daily living such as dressing,
bathing, and eating.
Aphasia
A speech-language pathologist can perform drills
and exercises with a person that include practice in
naming objects and following directions to try to
improve skills. The person learns the best way to
express himself of herself. Group therapy also is an
option, which focuses on structured discussions.
Developmental apraxia of speech
Treatment should focus on the coordination of
motor movements necessary during speech production, which includes controlling breathing. A speechlanguage pathologist teaches exercises to a person
with apraxia that will strengthen the jaws, lips, and
tongue to improve coordination during speech. The
therapist uses tactile, auditory, and visual feedback to
direct the brain to move the muscles used during
speech.

Developmental apraxia of speech
Some persons with apraxia may decide to use
alternative communication systems, such as a computer that transcribes and ‘‘speaks’’ what a person is
directing it to say. These augmentative systems should
only be used when a person is so severely impaired that
effective speech or communication isn’t possible.
Laryngeal cancer
In cases of a full laryngectomy, a hole is made in
the neck and, rather than using the mouth and nose to
talk and breath, the person must use the hole.
Once the larynx is removed, the person needs to
develop a new speech system without a voice. A speech
pathologist should follow one of three plans: esophageal speech, artificial larynx, or tracheoesophageal
puncture (TEP).


Esophageal speech. Without a larynx, a person is no
longer able to exhale air from the lungs through the
mouth to speak. Using esophageal speech, the person
inhales and traps the air in the throat, causing the
esophagus to vibrate and create sound.



Artificial larynx. A mechanical instrument can be
used that produces sound for some speech. These
devices can be held against the neck or used by
inserting a tube in the mouth.



Tracheoesophageal puncture. This is a popular
method in restoring speech production. During surgery, a hole is made between the trachea and esophagus and a valve is inserted into the hole. The person
breathes air into the lungs and then covers the hole in
the throat. During exhalation, the esophagus
vibrates and creates speech.

Laryngeal cancer
Depending on when the cancer is first detected,
and depending on the size of the cancer, the entire
larynx may not need to be removed. Radiation, chemotherapy, or partial removal can be done in lieu
of complete removal. In these cases, the voice may
be preserved although the quality likely will be
affected.
Orofacial myofunctional disorders
In cases where speech is affected, a speech pathologist should be consulted to help control breathing
problems and work on speech articulation. The lip,
palate, tongue, and facial muscles should be evaluated
so that errors in speech can be detected. Therapy
includes increasing awareness of the mouth and facial
muscles, as well as the posture of the mouth and
tongue. Muscle exercise can be done to increase
strength and control.
Stuttering
A treatment plan by a speech therapist includes
improving fluency and ease with which a person
speaks. Strategies include reducing the rate of speech
and using slower speech movements; articulating
lightly; and starting air flow for speech before any
other muscle movement.
3488

Stuttering
A person suffering from stuttering may employ
distraction strategies to help him or her stop stuttering. Typically, a person stuttering becomes frustrated
and embarrassed; subsequently, encouraging the person to think of something or do something else may
break the stuttering cycle.

Prognosis
Amyotrophic lateral sclerosis (ALS)
ALS patients often die of respiratory failure within
three to five years of being diagnosed, although some
persons have been known to survive as many as 10
years or longer.
GALE ENCYCLOPEDIA OF MEDICINE

Neurons—Nerve cells in the brain, brain stem, and
spinal cord that connect the nervous system and the
muscles.

American Speech-Language-Hearing Association. 1801
Rockville Pike, Rockville, MD 20852. (800) 638-8255.
<http://www.asha.org>.

Meghan Gourley

Speech disturbance see Aphasia
Aphasia
Persons with aphasia can improve and eventually
function in more typical public settings, and possibly
return to school or work.

Speech therapy see Rehabilitation
Sperm count see Semen analysis

Developmental apraxia of speech
With proper treatment, apraxia can be brought
under control and the person will be able to function
normally as an adult.
Laryngeal cancer
Full removal of the larynx removes the risk of a
cancer relapse, although other parts of the throat and
mouth can be affected.
Orofacial myofunctional disorders
A person can learn to control this disorder with
proper treatment and maintain normal speech and
breathing patterns.
Stuttering
With proper speech therapy, stuttering can be
controlled or eliminated.

Prevention
Laryngeal cancer
Persons should not engage in smoking or drug
abuse to decrease the risk of oral cancer.
Orofacial myofunctional disorders
In cases where the cause is evident, such as allergies or enlarged tonsils, a person should first remedy
that problem; perhaps have the tonsils removed and
treat allergies with medication.
Resources
BOOKS

Paul, Rhea. Language Disorders from Infancy through
Adolescence. 2nd ed. St. Louis: Mosby, Inc., 2001.
GALE ENCYCLOPEDIA OF MEDICINE

Spina bifida
Definition
Spina bifida is a serious birth abnormality in
which the spinal cord is malformed and lacks its
usual protective skeletal and soft tissue coverings.

Description
Spina bifida may appear in the body midline anywhere from the neck to the buttocks. In its most severe
form, termed spinal rachischisis, the entire spinal
canal is open, exposing the spinal cord and nerves.
More commonly, the abnormality appears as a localized mass on the back that is covered by skin or by the
meninges, the three-layered membrane that envelopes
the spina cord. Spina bifida is usually readily apparent
at birth because of the malformation of the back and
paralysis below the level of the abnormality.
Various forms of spina bifida are known as
meningomyelocele, myelomeningocele, spina bifida
aperta, open spina bifida, myelodysplasia, spinal dysraphism, spinal rachischisis, myelocele, and meningocele. The term meningocele is used when the spine
malformation contains only the protective covering
(meninges) of the spinal cord. The other terms indicate
involvement of the spinal cord and nerves in the malformation. A related term, spina bifida occulta, indicates that one or more of the bony bodies in the spine
are incompletely hardened, but that there is no
abnormality of the spinal cord itself.
Spina bifida occurs worldwide, but there has been
a steady downward trend in occurrence rates over the
past 50–70 years, particularly in regions of high prevalence. The highest prevalence rates, about one in 200
pregnancies, have been reported from certain northern
provinces in China. Intermediate prevalence rates,
about one in 1,000 pregnancies, have been found in
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Spina bifida

ORGANIZATIONS

KEY TERMS

Spina bifida

Central and South America. The lowest prevalence
rates, less than one in 2,000 pregnancies, have been
found in the European countries. The highest regional
prevalence in the United States of about one in 500
pregnancies has occurred in the Southeast.

Causes and symptoms
Spina bifida may occur as an isolated abnormality
or in the company of other malformations. As an
isolated abnormality, spina bifida is caused by the
combination of genetic factors and environmental
influences that bring about malformation of the
spine and spinal column. The specific genes and environmental influences that contribute to the many-factored causes of spina bifida are not completely known.
An insufficiency of folic acid is known to be one influential nutritional factor. Changes (mutations) in genes
involving the metabolism of folic acid are believed to
be significant genetic risk factors. The recurrence risk
after the birth of an infant with isolated spina bifida is
3–5%. Recurrence may be for spina bifida or another
type of spinal abnormality.
Spina bifida may arise because of chromosome
abnormalities, single gene mutations, or specific environmental insults such as maternal diabetes mellitus or
prenatal exposure to certain anticonvulsant drugs. The
recurrence risk varies with each of these specific
causes.
In most cases, spina bifida is obvious at birth
because of malformation of the spine. The spine may
be completely open, exposing the spinal cord and
nerves. More commonly, the spine abnormality
appears as a mass on the back covered by membrane
(meninges) or skin. Spina bifida may occur anywhere
from the base of the skull to the buttocks. About 75%
of abnormalities occur in the lower back (lumbar)
region. In rare instances, the spinal cord malformation
may occur internally, sometimes with a connection to
the gastrointestinal tract.
In spina bifida, many complications arise, dependent in part on the level and severity of the spine
malformation. As a rule, the nerves below the level
of the abnormality develop in a faulty manner and fail
to function, resulting in paralysis and loss of sensation
below the level of the spine malformation. Since most
abnormalities occur in the lumbar region, the lower
limbs are paralyzed and lack sensation. Furthermore,
the bowel and bladder have inadequate nerve connections, causing an inability to control bowel and bladder function. Most infants also develop hydrocephaly,
an accumulation of excess fluid in the four cavities of
the brain. At least one of every seven cases develop
3490

findings of Chiari II malformation, a condition in
which the lower part of the brain is crowded and
may be forced into the upper part of the spinal cavity.
There are a number of mild variant forms of spina
bifida, including multiple vertebral abnormalities,
skin dimples, tufts of hair, and localized areas of skin
deficiency over the spine. Two variants, lipomeningocele and lipomyelomeningocele, typically occur in the
lower back area (lumbar or sacral) of the spine. In
these conditions, a tumor of fatty tissue becomes isolated among the nerves below the spinal cord, which
may result in tethering of the spinal cord and complications similar to those with open spina bifida.

Diagnosis
Few disorders are to be confused with open spina
bifida. The diagnosis is usually obvious based on the
external findings at birth. Paralysis below the level of
the abnormality and fluid on the brain (hydrocephaly)
may contribute to the diagnosis. Other spine abnormalities such as congenital scoliosis and kyphosis, or soft
tissue tumors overlying the spine, are not likely to have
these accompanying findings. In cases in which there
are no external findings, the diagnosis is more difficult
and may not become evident until neurological
abnormalities or hydrocephaly develop weeks,
months, or years following birth.
Prenatal diagnosis may be made in most cases
with ultrasound examination after 12–14 weeks of
pregnancy. Many cases are also detected by the testing
of the mother’s blood for the level of alpha-fetoprotein
at about 16 weeks of pregnancy. If the spine malformation is not skin covered, alpha-fetoprotein from the
fetus’ circulation may leak into the surrounding
amniotic fluid, a small portion of which is absorbed
into the mother’s blood.

Treatment
Aggressive surgical and medical management
have improved the survival and function of infants
with spina bifida. Initial surgery may be carried out
during the first days of life, providing protection
against injury and infection. Subsequent surgery is
often necessary to protect against excessive curvature
of the spine, and in the presence of hydrocephaly, to
place a mechanical shunt to decrease the pressure and
amount of cerebrospinal fluid in the cavities of the
brain. Because of weakness or paralysis below the
level of the spine abnormality, most children will
require physical therapy, bracing, and other orthopedic assistance to enable them to walk. A variety of
GALE ENCYCLOPEDIA OF MEDICINE

Spina bifida

An infant with spina bifida. (Photograph by Biophoto Associates, Photo Researchers, Inc. Reproduced by permission.)

approaches including periodic bladder catheterization, surgical diversion of urine, and antibiotics are
used to protect urinary function.
Although most individuals with spina bifida have
normal intellectual function, learning disabilities or
mental retardation occur in a minority. This may
result, in part, from hydrocephaly and/or infections
of the nervous system. Children so affected may benefit from early educational intervention, physical therapy, and occupational therapy. Counseling to improve
self-image and lessen barriers to socialization becomes
important in late childhood and adolescence.
Open fetal surgery has been performed for spina
bifida during the last half of pregnancy. After direct
closure of the spine malformation, the fetus is returned
to the womb. By preventing chronic intrauterine exposure to mechanical and chemical trauma, prenatal surgery improves neurological function and leads to
fewer complications after birth. Fetal surgery is considered experimental, and results have been mixed.
Prevention of isolated spina bifida and other
spinal abnormalities has become possible during
recent decades. The major prevention is through the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Chiari II anomaly—A structural abnormality of the
lower portion of the brain (cerebellum and brain
stem) associated with spina bifida. The lower structures of the brain are crowded and may be forced
into the foramen magnum, the opening through
which the brain and spinal cord are connected.
Fetus—The term used to describe a developing
human infant from approximately the third month
of pregnancy until delivery. The term embryo is
used prior to the third month.
Hydrocephalus—The excess accumulation of cerebrospinal fluid around the brain, often causing
enlargement of the head.

use of a B vitamin, folic acid, for several months prior
to and following conception. The Centers for Disease
Control and Prevention recommend the intake of 400
micrograms of synthetic folic acid every day for all
women of childbearing years.
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Spinal cord injury

Prognosis
More than 80% of infants born with spina bifida
survive with surgical and medical management.
Although complications from paralysis, hydrocephaly, Chiari II malformation, and urinary tract deterioration threaten the well-being of the survivors, the
outlook for normal intellectual function is good.

for an SCI patient capable of independent living.
Lifetime costs may exceed one million dollars. Costs
may be three to four times higher for the SCI patient
who needs long-term institutional care. Overall costs
to the American economy in direct payments and lost
productivity are more than $10 billion per year.

Causes and symptoms
Resources

Causes

ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (888) 6634637. <http://www.modimes.org>.
National Birth Defects Prevention Network. Atlanta, GA
(770) 488-3550. <http://www.nbdpn.org>.
Shriners Hospitals for Children. International Shrine
Headquarters, 2900 Rocky Point Dr., Tampa, FL
33607-1460. (813) 281-0300. <http://
www.shrinershq.org>.
Spina Bifida Association of America. 4590 MacArthur Blvd.
NW, Suite 250, Washington, DC 20007-4226. (800)
621-3141 or (202) 944-3285. Fax: (202) 944-3295.

Roger E. Stevenson

The spinal cord is about as big around as the index
finger. It descends from the brain down the back
through hollow channels of the backbone. The spinal
cord is made of nerve cells (neurons). The nerve cells
carry sensory data from the areas outside the spinal
cord (periphery) to the brain, and they carry motor
commands from brain to periphery. Peripheral neurons are bundled together to make up the 31 pairs of
peripheral nerve roots. The peripheral nerve roots
enter and exit the spinal cord by passing through the
spaces between the stacked vertebrae. Each pair of
nerves is named for the vertebra from which it exits.
These are known as:


C1-8. These nerves enter from the eight cervical or
neck vertebrae.



T1-12. These nerves enter from the thoracic or chest
vertebrae.



L1-5. These nerves enter from the lumbar vertebrae
of the lower back.



S1-5. These nerves enter through the sacral or pelvic
vertebrae.



Coccygeal. These nerves enter through the coccyx or
tailbone.

Spina bifida occulta see Spina bifida

Spinal cord injury
Definition
Spinal cord injury is damage to the spinal cord
that causes loss of sensation and motor control.

Description
Approximately 10,000 new spinal cord injuries
(SCIs) occur each year in the United States. About
250,000 people are currently affected. Spinal cord
injuries can happen to anyone at any time of life.
The typical patient, however, is a man between the
ages of 19 and 26, injured in a motor vehicle accident
(about 50% of all SCIs), a fall (20%), an act of
violence (15%), or a sporting accident (14%).
Alcohol or other drug abuse plays an important role
in a large percentage of all spinal cord injuries. Six
percent of people who receive injuries to the lower
spine die within a year, and 40% of people who
receive the more frequent higher injuries die within
a year.
Short-term costs for hospitalization, equipment,
and home modifications are approximately $140,000
3492

Peripheral nerves carry motor commands to the
muscles and internal organs, and they carry sensations
from these areas and from the body’s surface. (Sensory
data from the head, including sight, sound, smell, and
taste, do not pass through the spinal cord and are not
affected by most SCIs.) Damage to the spinal cord
interrupts these signals. The interruption damages
motor functions that allow the muscles to move, sensory functions such as feeling heat and cold, and autonomic functions such as urination, sexual function,
sweating, and blood pressure.
Spinal cord injuries most often occur where the
spine is most flexible, in the regions of C5-C7 of the
neck, and T10-L2 at the base of the rib cage. Several
physically distinct types of damage are recognized.
Sudden and violent jolts to nearby tissues can jar the
cord. This jarring causes a temporary spinal concussion. Concussion symptoms usually disappear
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms
PARALYSIS AND LOSS OF SENSATION. The extent to
which movement and sensation are damaged depends
on the level of the spinal cord injury. Nerves leaving
the spinal cord at different levels control sensation and
movement in different parts of the body. The distribution is roughly as follows:


C1-C4: head and neck.



C3-C5: diaphragm (chest and breathing).



C5-T1: shoulders, arms and hands.



T2-T12: chest and abdomen (excluding internal
organs).



L1-L4: abdomen (excluding internal organs), buttocks, genitals, and upper legs.



L4-S1: legs.



S2-S4: genitals and muscles of the perineum.

Damage below T1, which lies at the base of the rib
cage, causes paralysis and loss of sensation in the legs
and trunk below the injury. Injury at this level usually
does no damage to the arms and hands. Paralysis of
the legs is called paraplegia. Damage above T1
involves the arms as well as the legs. Paralysis of all
four limbs is called quadriplegia or tetraplegia.
Cervical or neck injuries not only cause quadriplegia
but also may cause difficulty in breathing. Damage in
the lower part of the neck may leave enough diaphragm control to allow unassisted breathing.
Patients with damage at C3 or above, just below the
base of the skull, require mechanical assistance to
breathe.
Symptoms also depend on the extent of spinal
cord injury. A completely severed cord causes paralysis and loss of sensation below the wound. If the cord is
only partially severed, some function will remain
below the injury. Damage limited to the front portion
of the cord causes paralysis and loss of sensations of
pain and temperature. Other sensation may be preserved. Damage to the center of the cord may spare
the legs but paralyze the arms. Damage to the right or
GALE ENCYCLOPEDIA OF MEDICINE

left half causes loss of position sense, paralysis on the
side of the injury, and loss of pain and temperature
sensation on the opposite side.
DEEP VENOUS THROMBOSIS. Blood does not flow
normally to a paralyzed limb that is inactive for long
periods. The blood pools in the deep veins and forms
clots, a condition known as deep vein thrombosis. A
clot or thrombus can break free and lodge in smaller
arteries in the brain, causing a stroke, or in the lungs,
causing pulmonary embolism.
PRESSURE ULCERS. Inability to move also leads to
pressure ulcers or bed sores. Pressure ulcers form
where skin remains in contact with a bed or chair for
a long time. The most common sites of pressure ulcers
are the buttocks, hips, and heels.
SPASTICITY AND CONTRACTURE. A paralyzed limb
is incapable of active movement, but the muscle still has
tone, a constant low level of contraction. Normal muscle tone requires communication between the muscle
and the brain. Spinal cord injury prevents the brain
from telling the muscle to relax. The result is prolonged
muscle contraction or spasticity. Because the muscles
that extend and those that bend a joint are not usually
equal in strength, the involved joint is bent, often
severely. This constant pressure causes deformity. As
the muscle remains in the shortened position over several weeks or months, the tendons remodel and cause
permanent muscle shortening or contracture. When
muscles have permanently shortened, the inner surfaces
of joints, such as armpits or palms, cannot be cleaned
and the skin breaks down in that area.
HETEROTOPIC OSSIFICATION. Heterotopic ossification is an abnormal deposit of bone in muscles and
tendons that may occur after injury. It is most common in the hips and knees. Initially heterotopic ossification causes localized swelling, warmth, redness, and
stiffness of the muscle. It usually begins one to four
months after the injury and is rare after one year.
AUTONOMIC DYSREFLEXIA. Body organs that regulate themselves, such as the heart, gastrointestinal
tract, and glands, are controlled by groups of nerves
called autonomic nerves. Autonomic nerves emerge
from three different places: above the spinal column,
in the lower back from vertebrae T1-L4, and from the
lowest regions of the sacrum at the base of the spine. In
general, these three groups of autonomic nerves operate in balance. Spinal cord injury can disrupt this
balance, a condition called autonomic dysreflexia or
autonomic hyperreflexia. Patients with injuries at T6
or above are at greatest risk.

In autonomic dysreflexia, irritation of the skin,
bowel, or bladder causes a highly exaggerated
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Spinal cord injury

completely within several hours. A spinal contusion or
bruise is bleeding within the spinal column. The pressure from the excess fluid may kill spinal cord neurons.
Spinal compression is caused by some object, such as a
tumor, pressing on the cord. Lacerations or tears
cause direct damage to cord neurons. Lacerations
can be caused by bone fragments or missiles such as
bullets. Spinal transection describes the complete
severing of the cord. Most spinal cord injuries involve
two or more of these types of damage.

Spinal cord injury

Cervical region
(C1-C5)

Thoracic region
(T1-T12)

Lumbar region
(L1-L4)
Sacral region
(S1-S4)

LOSS OF BLADDER AND BOWEL CONTROL. Bladder
and bowel control require both motor nerves and the
autonomic nervous system. Both of these systems may
be damaged by SCI. When the autonomic nervous
system triggers an urge to urinate or defecate, continence is maintained by contracting the anal or urethral
sphincters. A sphincter is a ring of muscle that contracts to close off a passage or opening in the body.
When the neural connections to these muscles are
severed, conscious control is lost. In addition, loss of
feeling may prevent sensations of fullness from reaching the brain. To compensate, the patient may help
empty the bowel or bladder by using physical maneuvers that stimulate autonomic contractions before
they would otherwise begin. However, the patient
may not be able to relax the sphincters. If the sphincters cannot be relaxed, the patient will retain urine or
feces.

Retention of urine may cause muscular changes in
the bladder and urethral sphincter that make the problem worse. Urinary tract infection is common.
Retention of feces can cause impaction. Symptoms of
impaction include loss of appetite and nausea.
Untreated impaction may cause perforation of the
large intestine and rapid overwhelming infection.

The extent of sensory and motor loss resulting from a spinal
cord injury depends on the level of the injury because nerves
at different levels control sensation and movement in different parts of the body. The distribution is as follows: C1-C4:
head and neck; C3-C5: diaphragm; C5-T1: shoulders, arms,
and hands; T2-T12: chest and abdomen (excluding internal
organs); L1-L4: abdomen (excluding internal organs), buttocks, genitals, upper legs; L4-S3: legs; S2-S4: genitals, muscles of the perineum. (Illustration by Electronic Illustrators
Group.)

response from autonomic nerves. This response is
caused by the uncontrolled release of norepinephrine,
a hormone similar to adrenaline. Uncontrolled
release of norepinephrine causes a rapid rise in
blood pressure and a slowing of the heart rate.
These symptoms are accompanied by throbbing
headache, nausea, anxiety, sweating, and goose
bumps below the level of the injury. The elevated
blood pressure can rapidly cause loss of consciousness, seizures, cerebral hemorrhage, and death.
Autonomic dysreflexia is most often caused by an
over-full bladder or bladder infection, impaction or
hard impassable fecal mass in the bowel, or skin
irritation from tight clothing, sunburn, or other irritant. Inability to sense these irritants before the autonomic reaction begins is a major cause of dysreflexia.
3494

SEXUAL DYSFUNCTION. Men who have sustained
SCI may be unable to achieve an erection or ejaculate.
Sperm formation may be abnormal too, reducing fertility. Fertility and the ability to achieve orgasm are
less impaired for women. Women may still be able to
become pregnant and deliver vaginally with proper
medical care.

Diagnosis
The location and extent of spinal cord injury is
determined with computed tomography scans (CT
scans), magnetic resonance imaging (MRI) scans, and
x rays. X rays may be enhanced with an injected contrast dye.

Treatment
A person who may have a spinal cord injury
should not be moved. Treatment of SCI begins with
immobilization. This strategy prevents partial injuries
of the cord from severing it completely. Use of splints
to completely immobilize suspected SCI at the scene of
the injury has helped reduce the severity of spinal cord
injuries in the last two decades. Intravenous methylprednisone, a steroidal anti-inflammatory drug, is
given during the first 24 hours to reduce inflammation
and tissue destruction.
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Paralysis and loss of sensation
Some limited mobility and sensation may be
recovered, but the extent and speed of this recovery
cannot be predicted. Experimental electrical stimulation has been shown to allow some control of muscle
contraction in paraplegia. This experimental technique offers the possibility of unaided walking. Further
development of current control systems will be needed
before useful movement is possible outside the
laboratory.
The physical therapist focuses on mobility, to
maintain range of motion of affected limbs and reduce
contracture and deformity. Physical therapy helps
compensate for lost skills by using those muscles that
are still functional. It also helps to increase any residual strength and control in affected muscles. A physical therapist suggests adaptive equipment such as
braces, canes, or wheelchairs.
An occupational therapist works to restore ability
to perform the activities of daily living, such as eating
and grooming, with tools and new techniques. The
occupational therapist also designs modifications of
the home and workplace to match the individual
impairment.
A pulmonologist or respiratory therapist promotes airway hygiene through instruction in assisted
coughing techniques and postural drainage. The
respiratory professional also prescribes and provides
instruction in the use of ventilators, facial or nasal
masks, and tracheostomy equipment where necessary.

Electrical stimulation is sometimes used to promote
muscle movement to prevent pressure ulcers.
Spasticity and contracture
Range of motion (ROM) exercises help to prevent
contracture. Chemicals can be used to prevent contractures from becoming fixed when ROM exercise is
inadequate. Phenol or alcohol can be injected onto
the nerve or botulinum toxin directly into the muscle.
Botulinum toxin is associated with fewer complications, but it is more expensive than phenol and alcohol. Contractures can be released by cutting the
shortened tendon or transferring it surgically to a
different site on the bone where its pull will not cause
as much deformity. Such tendon transfers may also be
used to increase strength in partially functional
extremities.
Heterotopic ossification
Etidronate disodium (Didronel), a drug that regulates the body’s use of calcium, is used to prevent
heterotopic ossification. Treatment begins three weeks
after the injury and continues for 12 weeks. Surgical
removal of ossified tissue is possible.
Autonomic dysreflexia
Autonomic dysreflexia is prevented by bowel and
bladder care and attention to potential irritants. It is
treated by prompt removal of the irritant. Drugs to
lower blood pressure are used when necessary. People
with SCI should educate friends and family members
about the symptoms and treatment of dysreflexia,
because immediate attention is necessary.
Loss of bladder and bowel control
Normal bowel function is promoted through adequate fluid intake and a diet rich in fiber. Evacuation is
stimulated by deliberately increasing the abdominal
pressure, either voluntarily or by using an abdominal
binder.
Bladder care involves continual or intermittent
catheterization. The full bladder may be detected by
feeling its bulge against the abdominal wall. Urinary
tract infection is a significant complication of catheterization and requires frequent monitoring.

Pressure ulcers
Pressure ulcers are prevented by turning in bed at
least every two hours. The patient should be turned
more frequently when redness begins to develop in
sensitive areas. Special mattresses and chair cushions
can distribute weight more evenly to reduce pressure.
GALE ENCYCLOPEDIA OF MEDICINE

Sexual dysfunction
Counseling can help in adjusting to changes in
sexual function after spinal cord injury. Erection
may be enhanced through the same means used to
treat erectile dysfunction in the general population.
3495

Spinal cord injury

Rehabilitation after spinal cord injury seeks to
prevent complications, promote recovery, and make
the most of remaining function. Rehabilitation is a
complex and long-term process. It requires a team of
professionals, including a neurologist, physiatrist or
rehabilitation specialist, physical therapist, and occupational therapist. Other specialists who may be
needed include a respiratory therapist, vocational
rehabilitation counselor, social worker, speech-language pathologist, nutritionist, special education teacher, recreation therapist, and clinical psychologist.
Support groups provide a critical source of information, advice, and support for SCI patients.

Spinal cord tumors

KEY TERMS
Autonomic nervous system—The part of the nervous system that controls involuntary functions
such as sweating and blood pressure.
Botulinum toxin—Any of a group of potent bacterial toxins or poisons produced by different strains of
the bacterium Clostridium botulinum.
Computed tomography (CT)—An imaging technique in which cross-sectional x rays of the body are
compiled to create a three-dimensional image of
the body’s internal structures.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Motor—Of or pertaining to motion, the body apparatus involved in movement, or the brain functions
that direct purposeful activity.
Motor nerve—Motor or efferent nerve cells carry
impulses from the brain to muscle or organ
tissue.
Peripheral nervous system—The part of the nervous system that is outside the brain and spinal
cord. Sensory, motor, and autonomic nerves are
included.
Postural drainage—The use of positioning to drain
secretions from the bronchial tubes and lungs into
the trachea or windpipe.
Range of motion (ROM)—The range of motion of a
joint from full extension to full flexion (bending)
measured in degrees like a circle.
Sensory nerves—Sensory or afferent nerves carry
impulses of sensation from the periphery or outward parts of the body to the brain. Sensations
include feelings, impressions, and awareness of
the state of the body.
Voluntary—An action or thought undertaken or
controlled by a person’s free will or choice.

Prognosis
The prognosis of SCI depends on the location
and extent of injury. Injuries of the neck above
C4 with significant involvement of the diaphragm
hold the gravest prognosis. Respiratory infection is
one of the leading causes of death in long-term
SCI. Overall, 85% of SCI patients who survive the
3496

first 24 hours are alive 10 years after their injuries.
Recovery of function is impossible to predict. Partial
recovery is more likely after an incomplete wound
than after the spinal cord has been completely
severed.

Prevention
Risk of spinal cord injury can be reduced through
prevention of the accidents that lead to it. Chances of
injury from automobile accidents, the major cause of
SCIs, can be significantly reduced by driving at safe
speeds, avoiding alcohol while driving, and using seat
belts.
Resources
ORGANIZATIONS

National Spinal Cord Injury Association. 8300 Colesville
Road, Silver Spring, Maryland 20910. (301) 588-6959.
<http://www.erols.com/nscia>.

Richard Robinson

Spinal cord tumors
Definition
A spinal cord tumor is a benign or cancerous
growth in the spinal cord, between the membranes
covering the spinal cord, or in the spinal canal. A
tumor in this location can compress the spinal cord
or its nerve roots; therefore, even a noncancerous
growth can be disabling unless properly treated.

Description
The spinal cord contains bundles of nerves that
carry messages betweent the brain and the body.
Because the spinal cord is rigidly encased in bone,
any tumor that grows on or near it can compress the
nerves, and interfere in this communication. About
10,000 Americans develop spinal cord tumors each
year, and about 40% of these are cancerous. Similar
to brain tumors, spinal cord growths are rare.
Newly formed tumors that begin within the spinal
cord are unusual, especially among children and the
elderly. More typically, tumors originate elsewhere in
the body and move through the bloodstream (metastasize) to the spinal cord.
GALE ENCYCLOPEDIA OF MEDICINE

Scientists don’t know what causes these tumors,
although the noncancerous growths may be hereditary
or present since birth.
When the tumor presses on the spinal cord, it
causes symptoms including;


back pain



severe or burning pain in other parts of the body



numbness or cold



progressive loss of muscle strength or sensation in the
legs



loss of bladder or bowel control

A tumor in the top of the spinal column can cause
pain radiating from the arms or neck; a tumor in the
lower spine may cause leg or back pain. If there are
several tumors in different areas of the spinal cord at
the same time, it may cause symptoms in a variety of
spots on the body.

KEY TERMS
Computed tomography scans (CT Scan)—The CT
scan combines an X-ray with a computer to create a
detailed picture of the spinal cord. It may help to
determine the type of tumor, locate swelling or
bleeding, and check results of treatment.
Magnetic resonance imaging (MRI) — MRI is an
imaging technique that uses a magnetic field to
scan the body’s tissues and structures. It gives a
better picture of tumors located near bone than
does a CT scan, without the risk of radiation, and
can provide a three-dimensional image of the
tumor.
Myelogram—A myelogram is an x ray exam of the
spinal cord, nerves and other tissues within the
spinal cord that are highlighted by injected contrast
dye.

Prognosis
Diagnosis
Suspected spinal cord compression, by tumor, is a
medical emergency. Prompt intervention may prevent
paralysis.
If a neurological exam and review of symptoms
suggest a spinal cord tumor, the doctor may order
some of these additional tests:


MRI or CT scan



myelography



blood and spinal fluid studies



x rays of the spine



biopsy



radionuclide bone scan

Treatment
If the tumor is malignant and has metastasized,
treatment depends on the type of the primary cancer. Surgery is usually the first step in treating
benign and malignant tumors outside the spinal
cord. Tumors inside the spinal cord may not be
able to be completely removed with surgery. If
they can not be, radiation and chemotherapy treatments may be effective. Treatment also may include
pain relievers and cortisone drugs to lessen swelling
around the tumor, and ease pressure on the spinal
cord.
GALE ENCYCLOPEDIA OF MEDICINE

Early diagnosis and treatment can produce a
higher success rate. Long-term survival also depends
on the tumor’s type, location, and size. Surgery to
remove the bone around the cord can ease pressure
on the spinal nerves and nerve pathways, which will
usually ease pain and other symptoms; however, it
may make walking more difficult. Physical therapy
and rehabilitation may help.

Prevention
Since spinal cord tumors usually are the result of a
cancer that has first appeared elsewhere in the body,
early detection of cancer in other organs may prevent
spinal cord tumors. Lifestyle changes, as stopping
smoking, to lower the risk of the development of
other types of cancer, may also help.
Resources
ORGANIZATIONS

National Institute of Neurological Disorders and Stroke.
P.O. Box 5801, Bethesda, MD 20824. (800) 352-9424.
<http://www.ninds.nih.gov/index.htm>.

Carol A. Turkington

Spinal fluid analysis see Cerebrospinal fluid
(CSF) analysis
Spinal fusion see Disk removal
3497

Spinal cord tumors

Causes and symptoms

Spinal instrumentation

Spinal instrumentation
Definition
Spinal instrumentation is a method of straightening and stabilizing the spine after spinal fusion, by
surgically attaching hooks, rods, and wire to the
spine in a way that redistributes the stresses on the
bones and keeps them in proper alignment.

Purpose
Spinal instrumentation is used to treat instability
and deformity of the spine. Instability occurs when the
spine no longer maintains its normal shape during
movement. Such instability results in nerve damage,
spinal deformities, and disabling pain. Spinal deformities may be caused by:


birth defects



fractures



marfan syndrome



neurofibromatosis



neuromuscular diseases



severe injuries



tumors

Curvature of the spine (scoliosis) is usually treated with spinal fusion and spinal instrumentation.
Scoliosis is a disorder of unknown origin. It causes
bending and twisting of the spine that eventually
results in distortion of the chest and back. About
85% of cases occur in girls between the ages of 12
and 15, who are experiencing adolescent growth
spurt.
Spinal instrumentation serves three purposes. It
provides a stable, rigid column that encourages bones
to fuse after spinal-fusion surgery. Second, it redirects
the stresses over a wider area. Third, it restores the
spine to its proper alignment.
Different types of spinal instrumentation are used
to treat different spinal problems. Several common
types of spinal instrumentation are explained below.
Although the details of the insertion of rods, wires,
and hooks varies, the purpose of all spinal instrumentation is the same—to correct and stabilize the
backbone.
Harrington rod
The Harrington Rod is one of the oldest and most
proven forms of spinal instrumentation. It is used to
3498

straighten and stabilize the spine when curvature is
greater than 60 degrees. It is an appropriate treatment
for scoliosis.
Advantages of the Harrington rod are its relative
simplicity of installation, the low rate of complications, and a proven record of reducing curvature of
the spine. The main disadvantage is that the patient
must remain in a body cast for about six months, then
wear a brace for another three to six months while the
bone fusion solidifies.
Luque rod
Luque rods are custom contoured metal rods
that are fixed to each segment (vertebra) in the
affected part of the spine. The main advantage is
that the patient may not need to wear a cast or
brace after the procedure. The main disadvantage is
that the risk of injury to the nerves and spinal cord is
higher than with a some other forms of instrumentation. This is because wires must be threaded through
each vertebra near the spinal column, increasing the
risk of such damage. Luque rods are sometimes used
to treat scoliosis.
Drummond instrumentation
Drummond instrumentation, also called HarriDrummond instrumentation, uses a Harrington rod
on the concave side of the spine and a Luque rod on
the convex side. The advantage is that each vertebra
segment is fixed, with the risk of nerve injury
decreased over Luque rod instrumentation. The disadvantage is that, like Harrington rod instrumentation, the patient must wear a cast and a brace after
surgery.
Cotrel-Dubousset instrumentation
Cotrel-Dubousset instrumentation uses hooks
and rods in a cross-linked pattern to realign the
spine and redistribute the biomechanical stress. The
main advantage of Cotrel-Dubousset instrumentation is that, because of the extensive cross-linking,
the patient may have to wear a cast or brace after
surgery. The disadvantage is the complexity of the
operation and the number of hooks and cross-links
that may fail.
Zeilke instrumentation
Zeilke instrumentation is similar to CotrelDubousset instrumentation, but is used to treat double
curvature of the spine. It requires wearing a brace for
many months after surgery.
GALE ENCYCLOPEDIA OF MEDICINE

The Kaneda device is used to treat fractured thoracic
or lumbar vertebrae when it is suspected that bone fragments are present in the spinal canal. Variations on the
basic forms of spinal instrumentation, such as Wisconsin
instrumentation, are being refined as technology
improves. A physician chooses the proper type of instrumentation based on the type of disorder, the age and
health of the patient, and on the physician’s experience.

Precautions
Since the hooks and rods of spinal instrumentation are anchored in the bones of the back, spinal
instrumentation should not be performed on people
with serious osteoporosis. To overcome this limitation,
techniques are being explored that help anchor instrumentation in fragile bones.

KEY TERMS
Lumbar vertebrae—The vertebrae of the lower
back below the level of the ribs.
Marfan syndrome—A rare hereditary defect that
affects the connective tissue.
Neurofibromatosis—A rare hereditary disease that
involves the growth of lesions that may affect the
spinal cord.
Osteoporosis—A bone disorder, usually seen in the
elderly, in which the boned become increasingly
less dense and more brittle.
Spinal fusion—An operation in which the bones of
the lower spine are permanently joined together
using a bone graft obtained usually from the hip.
Thoracic vertebrae—The vertebrae in the chest
region to which the ribs attach.

Description
Spinal instrumentation is performed by a neuro
and/or orthopedic surgical team with special experience in spinal operations. The surgery is done in a
hospital under general anesthesia. It is done at the
same time as spinal fusion.
The surgeon strips the muscles away from the area
to be fused. The surface of the bone is peeled away. A
piece of bone is removed from the hip and placed
along side the area to be fused. The stripping of the
bone helps the bone graft to fuse.
After the fusion site is prepared, the rods, hooks,
and wires are inserted. There is some variation in how
this is done based on the spinal instrumentation chosen. In general, Harrington rods are the simplest
instrumentation to install, and Cotrel-Dubousset
instrumentation is the most complex and risky. Once
the rods are in place, the incision is closed.

Preparation
Spinal fusion with spinal instrumentation is major
surgery. The patient will undergo many tests to determine that nature and exact location of the back problem.
These tests are likely to include x rays, magnetic resonance imaging (MRI), computed tomography scans (CT
scans), and myleograms. In addition, the patient will
undergo a battery of blood and urine tests, and possibly
an electrocardiogram to provide the surgeon and
anesthesiologist with information that will allow the
operation to be performed safely. In Harrington rod
instrumentation, the patient may be placed in traction
or an upper body cast to stretch contracted muscles
before surgery.
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare
After surgery, the patient will be confined to bed.
A catheter is inserted so that the patient can urinate
without getting up. Vital signs are monitored, and the
patient’s position is changed frequently so that bedsores do not develop.
Recovery from spinal instrumentation can be a
long, arduous process. Movement is severely limited
for a period of time. In certain types of instrumentation, the patient is put in a cast to allow the realigned
bones to stay in position until healing takes place. This
can be as long as six to eight months. Many patients
will need to wear a brace after the cast is removed.
During the recovery period, the patient is taught
respiratory exercises to help maintain respiratory
function during the time of limited mobility. Physical
therapists assist the patient in learning self-care and in
performing strengthening and range of motion exercises. Length of hospital stay depends on the age and
health of the patient, as well as the specific problem
that was corrected. The patient can expect to remain
under a physician’s care for many months.

Risks
Spinal instrumentation carries a significant risk of
nerve damage and paralysis. The skill of the surgeon
can affect the outcome of the operation, so patients
should look for a hospital and surgical team that has a
lot of experience doing spinal procedures.
3499

Spinal instrumentation

Other forms of instrumentation

Spinal stenosis

After surgery there is a risk of infection or an
inflammatory reaction due to the presence of the foreign material in the body. Serious infection of the
membranes covering the spinal cord and brain can
occur. In the long-term, the instrumentation may
move or break, causing nerve damage and requiring
a second surgery. Some bone grafts do not heal well,
lengthening the time the patient must spend in a cast or
brace, or necessitating additional surgery. Casting and
wearing a brace may take an emotional toll, especially
on young people. Patients who have had spinal instrumentation must avoid contact sports, and, for the rest
of their lives, eliminate situations that will abnormally
put stress on their spines.

Normal results
Many young people with scoliosis heal with significantly improved alignment of the spine. Results of
spinal instrumentation done for other conditions vary
widely.
Resources
ORGANIZATIONS

National Scoliosis Foundation. 5 Cabot Place, Stoughton,
MA 020724. (800) 673-6922. <http://
www.scoliosis.org>.
OTHER

Orthogate. <http://owl.orthogate.org/>.

Tish Davidson, A.M.

Spinal meningitis see Meningitis

Spinal stenosis
Definition
Spinal stenosis is any narrowing of the spinal
canal that causes compression of the spinal nerve
cord. Spinal stenosis causes pain and may cause loss
of some body functions.

Description
Spinal stenosis is a progressive narrowing of the
opening in the spinal canal. The spine is a long series of
bones called vertebrae. Between each pair of vertebra is
a fibrous intervertebral disk. Collectively, the vertebrae
and disks are called the backbone. Each vertebra has a
hole through it. These holes line up to form the spinal
canal. A large bundle of nerves called the spinal cord
3500

runs through the spinal canal. This bundle of 31 nerves
carries messages between the brain and the various
parts of the body. At each vertebra, some smaller nerves
branch out from these nerve roots to serve the muscles
and tissue in the immediate area. When the spinal canal
narrows, nerve roots in the spinal cord are squeezed.
Pressure on the nerve roots causes chronic pain and loss
of control over some functions because communication
with the brain is interrupted. The lower back and legs
are most affected by spinal stenosis. The nerve roots
that supply the legs are near the bottom of the spinal
cord. The pain gets worse after standing for a long time
and after some forms of exercise. The posture required
by these physical activities increases the stress on the
nerve roots. Spinal stenosis usually affects people over
50 years of age. Women have the condition more frequently than men do.
Cervical spinal stenosis is a narrowing of the vertebrae of the neck (cervical vertebrae). The disease and
its effects are similar to stenosis in the lower spine. A
narrower opening in the cervical vertebrae can also
put pressure on arteries entering the spinal column,
cutting off the blood supply to the remainder of the
spinal cord.

Causes and symptoms
Spinal stenosis causes pain in the buttocks, thigh,
and calf and increasing weakness in the legs. The
patient may also have difficulty controlling bladder
and bowel functions. The pain of spinal stenosis seems
more severe when the patient walks downhill. Spinal
stenosis can be congenital, acquired, or a combination.
Congenital spinal stenosis is a birth defect. Acquired
spinal stenosis develops after birth. It is usually a consequence of tissue destruction (degeneration) caused by
an infectious disease or a disease in which the immune
system attacks the body’s own cells (autoimmune disease). The two most common causes of spinal stenosis
are birth defect and progressive degeneration of the
tissue of the joints (osteoarthritis). Other causes include
improper alignment of the vertebrae as in spondylolisthesis, destruction of bone tissue as in Paget’s disease,
or an overgrowth of bone tissue as in diffuse idiopathic
skeletal hyperostosis. The spinal canal is usually more
than 0.5 in (12 mm) in diameter. A smaller diameter
indicates stenosis. The diameter of the cervical spine
ranges is 0.6–1 in (15–12 mm). Any opening under 0.5
in (13 mm)in diameter is considered evidence of stenosis. Acquired spinal stenosis usually begins with degeneration of the intervertebral disks or the surfaces of the
vertebrae or both. In trying to heal this degeneration,
the body builds up the spinal column. In the process,
the spinal canal can become narrower.
GALE ENCYCLOPEDIA OF MEDICINE

The physician must determine that the symptoms
are caused by spinal stenosis. Conditions that can
cause similar symptoms include a slipped (herniated)
intervertebral disk, spinal tumors, and disorders of the
blood flow (circulatory disorders). Spinal stenosis
causes back and leg pain. The leg pain is usually
worse when the patient is standing or walking. Some
forms of spinal stenosis are less painful when the
patient is riding an exercise bike because the forward
tilt of the body changes the pressure in the spinal
column. Doppler scanning can trace the flow of
blood to determine whether the pain is caused by
circulatory problems. X-ray images, computed tomography scans (CT scans), and magnetic resonance imaging (MRI) scans can reveal any narrowing of the
spinal canal. Electromyography, nerve conduction
velocity, or evoked potential studies can locate problems in the muscles indicating areas of spinal cord
compression.

Treatment
Mild cases of spinal stenosis may be treated with
rest, nonsteroidal anti-inflammatory drugs (such as
aspirin), and muscle relaxants. Spinal stenosis can be
a progressive disease, however, and the source of pressure may have to be surgically removed (surgical
decompression) if the patient is losing control over
bladder and bowel functions. The surgical procedure
removes bone and other tissues that have entered the
spinal canal or put pressure on the spinal cord. Two
vertebrae may be fused, to eliminate improper alignment, such as that caused by spondylolisthesis. For
surgery, patients lie on their sides or in a modified
kneeling position. This position reduces bleeding and
places the spine in proper alignment. Alignment is
especially important if vertebrae are to be fused.
Surgical decompression can eliminate leg pain and
restore control of the legs, bladder, and bowels, but
usually does not eliminate lower back pain. Physical
therapy and massage can help reduce the symptoms of
spinal stenosis. An exercise program should be developed to increase flexibility and mobility. A brace or
corset may be worn to improve posture. Activities that
place stress on the lower back muscles should be
avoided.

Prognosis
Surgical decompression does not stop the degenerative processes that cause spinal stenosis, and the
condition can develop again. Nevertheless, most
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Computed tomography (CT) Scans—An imaging
technique in which cross-sectional x rays of the
body are compiled to create a three-dimensional
image of the body’s internal structures.
Congenital—Present before birth. The term is used to
describe disorders that developed in the fetal stage.
Doppler scanning—A procedure in which ultrasound images are used to watch a moving structure
such as the flow of blood or the beating of the heart.
Electromyography—A test that uses electrodes to
record the electrical activity of muscle. The information gathered is used to find disorders of the
nerves that serve the muscles.
Evoked potential—A test of nerve response that
uses electrodes placed on the scalp to measure
brain reaction to a stimulus such as a touch.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.
Nerve conduction velocity test—A test that measures the time it takes a nerve impulse to travel a
specific distance over the nerve after electronic
stimulation.
Stenosis—The narrowing or constriction of a channel or opening.

patients achieve good results with surgical decompression. The patient will probably continue to have lower
back pain after the surgical procedure.
Resources
BOOKS

Berkow, Robert, editor. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

John T. Lohr, PhD

Spinal tap see Cerebrospinal fluid (CSF)
analysis
Spirometry see Pulmonary function test
Spleen, enlarged see Hypersplenism
Spleen removal see Splenectomy
3501

Spinal stenosis

Diagnosis

Splenectomy

Splenectomy has been regarded as the definitive
treatment for this disease and is effective in about
70% of chronic ITP cases. More recently, however,
the introduction of new drugs in the treatment of ITP
has reopened the question as to whether splenectomy
is always the best treatment option.

Splenectomy
Definition
Splenectomy is the surgical removal of the spleen,
which is an organ that is part of the lymphatic system.
The spleen is a dark-purple, bean-shaped organ located
in the upper left side of the abdomen, just behind the
bottom of the rib cage. In adults, the spleen is about 4.8
X 2.8 X 1.6 in (12 X 7 X 4 cm) in size, and weighs about
4–5 oz (113–14 zg). Its functions include a role in the
immune system; filtering foreign substances from the
blood; removing worn-out blood cells from the blood;
regulating blood flow to the liver; and sometimes storing blood cells. The storage of blood cells is called
sequestration. In healthy adults, about 30% of blood
platelets are sequestered in the spleen.



Trauma. The spleen can be ruptured by blunt as well
as penetrating injuries to the chest or abdomen. Car
accidents are the most common cause of blunt traumatic injury to the spleen.



Abscesses in the spleen. These are relatively uncommon but have a high mortality rate.



Rupture of the splenic artery. Rupture sometimes
occurs as a complication of pregnancy.



Hereditary elliptocytosis. This is a relatively rare
disorder. It is similar to HS in that it is characterized
by red blood cells with defective membranes that are
destroyed by the spleen.

Purpose
Splenectomies are performed for a variety of different reasons and with different degrees of urgency. Most
splenectomies are done after the patient has been diagnosed with hypersplenism. Hypersplenism is not a specific
disease but a group of symptoms, or syndrome, that can
be produced by a number of different disorders. It is
characterized by enlargement of the spleen (splenomegaly), defects in the blood cells, and an abnormally high
turnover of blood cells. It is almost always associated
with splenomegaly caused by specific disorders such as
cirrhosis of the liver or certain cancers. The decision to
perform a splenectomy depends on the severity and prognosis of the disease that is causing the hypersplenism.

Splenectomy sometimes necessary
In other disorders, the spleen may or may not be
removed.


Hodgkin’s disease, a serious form of cancer that
causes lymph nodes to enlarge. Splenectomy is
often performed in order to find out how far the
disease has progressed.



Thrombotic thrombocytopenic purpura (TTP). TTP
is a rare disorder marked by fever, kidney failure, and
an abnormal decrease in the number of platelets.
Splenectomy is one part of treatment for TTP.



Autoimmune hemolytic disorders. These disorders
may appear in patients of any age but are most
common in patients over 50. The red blood cells are
destroyed by antibodies produced by the patient’s
own body (autoantibodies).



Myelofibrosis. Myelofibrosis is a disorder in which
bone marrow is replaced by fibrous tissue. It produces severe and painful splenomegaly. Splenectomy
does not cure myelofibrosis but may be performed to
relieve pain caused by the swollen spleen.



Thalassemia. Thalassemia is a hereditary form of
anemia that is most common in people of
Mediterranean origin. Splenectomy is sometimes
performed if the patient’s spleen has become painfully enlarged.

Splenectomy always necessary
There are two diseases for which splenectomy is
the only treatment—primary cancers of the spleen and
a blood disorder called hereditary spherocytosis (HS).
In HS, the absence of a specific protein in the red
blood cell membrane leads to the formation of relatively fragile cells that are easily damaged when they
pass through the spleen. The cell destruction does not
occur elsewhere in the body and ends when the spleen
is removed. HS can appear at any age, even in newborns, although doctors prefer to put off removing the
spleen until the child is five or six years old.
Splenectomy usually necessary
There are some disorders in which splenectomy is
usually recommended. They include:


Immune (idiopathic) thrombocytopenic purpura
(ITP). ITP is a disease involving platelet destruction.

3502

Precautions
Patients should be carefully assessed regarding the
need for a splenectomy. Because of the spleen’s role in
GALE ENCYCLOPEDIA OF MEDICINE

The most important part of the assessment is the
measurement of splenomegaly. The normal spleen
cannot be felt when the doctor examines the patient’s
abdomen. A spleen that is large enough to be felt
indicates splenomegaly. In some cases the doctor will
hear a dull sound when he or she thumps (percusses)
the patient’s abdomen near the ribs on the left side.
Imaging studies that can be used to demonstrate splenomegaly include ultrasound tests, technetium-99m
sulfur colloid imaging, and CT scans. The rate of
platelet or red blood cell destruction by the spleen
can be measured by tagging blood cells with radioactive chromium or platelets with radioactive indium.

Description
Complete splenectomy
REMOVAL OF ENLARGED SPLEEN. Splenectomy is
performed under general anesthesia. The most common technique is used to remove greatly enlarged
spleens. After the surgeon makes a cut (incision) in
the abdomen, the artery to the spleen is tied to prevent
blood loss and reduce the spleen’s size. It also helps
prevent further sequestration of blood cells. The surgeon detaches the ligaments holding the spleen in place
and removes it. In many cases, tissue samples will be
sent to a laboratory for analysis.
REMOVAL OF RUPTURED SPLEEN. When the spleen
has been ruptured by trauma, the surgeon approaches
the organ from its underside and fastens the splenic
artery.

In some cases, the doctor may prefer conservative
(nonsurgical) management of a ruptured spleen, most
often when the patient’s blood pressure is stable and
there are no signs of other abdominal injuries. In the
case of multiple abdominal trauma, however, the
spleen is usually removed.
Partial splenectomy
In some cases the surgeon removes only part of
the spleen. This procedure is considered by some to be
GALE ENCYCLOPEDIA OF MEDICINE

a useful compromise that reduces pain from an
enlarged spleen while leaving the patient less vulnerable to infection. Long-term follow-up of the results of
partial splenectomies has not yet been done.
Laparoscopic splenectomy
Laparoscopic splenectomy, or removal of the
spleen through several small incisions, has been more
frequently used in recent years. Laparoscopic surgery
involves the use of surgical instruments, with the assistance of a tiny camera and video monitor.
Laparoscopic procedures reduce the length of hospital
stay, the level of post-operative pain, and the risk of
infection. They also leave smaller scars. Laparoscopic
splenectomy is not, however, the best option for many
patients.
Laparoscopic splenectomy is gaining increased
acceptance in the early 2000s as an alternative to
open splenectomy for a wide variety of disorders,
although splenomegaly still presents an obstacle to
laparoscopic splenectomy; massive splenomegaly has
been considered a contraindication. In patients with
enlarged spleens, however, laparoscopic splenectomy
is associated with less morbidity, decreased transfusion
rates, and shorter hospital stays than when the open
approach is used. Patients with enlarged spleens
usually have more severe hematologic diseases related
to greater morbidity; therefore, laparoscopic splenectomy has potential advantages.
The most frequent serious complication following
laparoscopic splenectomy is damage to the pancreas.
Application of a hydrogel sealant to the pancreas
during surgery, however, appears to significantly
reduce the risk of leakage from the pancreas.
Splenic embolization
Splenic embolization is an alternative to splenectomy that is used in some patients who are poor surgical risks. Embolization involves plugging or blocking
the splenic artery to shrink the size of the spleen. The
substances that are injected during this procedure
include polyvinyl alcohol foam, polystyrene, and silicone. Embolization is a technique that needs further
study and refinement.

Preparation
Preoperative preparation for nonemergency splenectomy includes:


Correction of abnormalities of blood clotting and the
number of red blood cells.
3503

Splenectomy

protecting people against infection, it should not be
removed unless necessary. The operation is relatively
safe for young and middle-aged adults. Older adults,
especially those with cardiac or pulmonary disease, are
more vulnerable to post-surgical infections.
Thromboembolism following splenectomy is another
complication for this patient group, which has about
10% mortality following the surgery. Splenectomies
are performed in children only when the benefits outweigh the risks.

Splenectomy

Spleen
Splenic artery

Stomach
Retractor

Splenectomy is the surgical removal of the spleen. This procedure is performed as a last result in most diseases involving the
spleen. In some cases, however, splenectomy does not address the underlying causes of splenomegaly or other conditions
affecting the spleen. (Illustration by Electronic Illustrators Group.)



Treatment of any infections.



Control of immune reactions. Patients are usually
given protective vaccinations about a month before
surgery. The most common vaccines used are
Pneumovax or Pnu-Imune 23 (against pneumococcal
infections) and Menomune-A/C/Y/W-135 (against
meningococcal infections).

Aftercare
Immediately following surgery, patients should
follow the physician’s instructions and take all medications intended to prevent infection. Blood transfusions may be indicated for some patients to replace
defective blood cells. The most important part of
aftercare, however, is long-term caution regarding
vulnerability to infection. Patients should see their
doctor at once if they have a fever or any other sign
of infection, and avoid travel to areas where exposure
to malaria or similar diseases is likely. Children with
splenectomies may be kept on antibiotic therapy until
they are 16 years old. All patients can be given a
3504

booster dose of pneumococcal vaccine five to 10
years after splenectomy.

Risks
The chief risk following splenectomy is overwhelming bacterial infection, or postsplenectomy sepsis. This vulnerability results from the body’s
decreased ability to clear bacteria from the blood,
and lowered levels of a protein in blood plasma that
helps to fight viruses (immunoglobulin M). The risk of
dying from infection after splenectomy is highest in
children, especially in the first two years after surgery.
The risk of postsplenectomy sepsis can be reduced by
vaccinations before the operation. Some doctors also
recommend a two-year course of penicillin following
splenectomy or long-term treatment with ampicillin.
Other risks following splenectomy include inflammation of the pancreas and collapse of the lungs. In
some cases, splenectomy does not address the underlying causes of splenomegaly or other conditions.
Excessive bleeding after the operation is an additional
GALE ENCYCLOPEDIA OF MEDICINE

Embolization—An alternative to splenectomy that
involves injecting silicone or similar substances into
the splenic artery to shrink the size of the spleen.
Hereditary spherocytosis (HS)—A blood disorder
in which the red blood cells are relatively fragile and
are damaged or destroyed when they pass through
the spleen. Splenectomy is the only treatment for HS.
Hypersplenism—A syndrome marked by enlargement of the spleen, defects in one or more types of
blood cells, and a high turnover of blood cells.
Immune or idiopathic thrombocytopenic purpura
(ITP)—A blood disease that results in destruction of
platelets, which are blood cells involved in
clotting.
Laparoscope—An instrument used to view the
abdominal cavity through a small incision and perform surgery on a small area, such as the spleen.
Pneumovax—A vaccine that is given to splenectomy
patients to protect them against bacterial infections.
Other vaccines include Pnu-Imune and Menomune.
Sepsis—A generalized infection of the body, most
often caused by bacteria.
Sequestration—A process in which the spleen
withdraws some normal blood cells from circulation and holds them in case the body needs extra
blood in an emergency. In hypersplenism, the
spleen sequesters too many blood cells.
Splenomegaly—Abnormal enlargement of the
spleen.
Thromboembolism—A clot in the blood that forms
and blocks a blood vessel. It can lead to infarction,
or death of the surrounding tissue due to lack of
blood supply.

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disorders of the Spleen.’’ Section 11, Chapter 141 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Wilkins, Bridget S., and Dennis H. Wright. Illustrated
Pathology of the Spleen. Cambridge, UK:Cambridge
University Press, 2000.
PERIODICALS

Balague, C., E. M. Targarona, G. Cerdan, et al. ‘‘LongTerm Outcome after Laparoscopic Splenectomy
Related to Hematologic Diagnosis.’’ Surgical
Endoscopy 18 (August 2004): 1283–1287.)
Bemelman, W. A., et al. ‘‘Hand-assisted Laparoscopic
Splenectomy.’’ Surgical Endoscopy 14, no. 11
(November 2000): 997–8.
Bjerke, H. Scott, MD, and Janet S. Bjerke, MSN. ‘‘Splenic
Rupture.’’ eMedicine June 19, 2002. <http://www.emedicine.com/med/topic2792.htm>.
Bolton-Maggs, P. H., R. F. Stevens, N. J. Dodd, et al.
‘‘Guidelines for the Diagnosis and Management of
Hereditary Spherocytosis.’’ British Journal of
Haematology 126 (August 2004): 455–474.
Brigden, M.L. ‘‘Detection, Education and Management of
the Asplenic or Hyposplenic Patient.’’ American Family
Physician 63, no. 3: 499–506, 508.
Kahn, M. J., and K. R. McCrae. ‘‘Splenectomy in Immune
Thrombocytopenic Purpura: Recent Controversies and
Long-term Outcomes.’’ Current Hematology Reports 3
(September 2004): 317–323.
Lo, A., A. M. Matheson, and D. Adams. ‘‘Impact of
Concomitant Trauma in the Management of Blunt
Splenic Injuries.’’ New Zealand Medical Journal 117
(September 10, 2004): U1052.
Rosen, M., R. M. Walsh, and J. R. Goldblum. ‘‘Application
of a New Collagen-Based Sealant for the Treatment of
Pancreatic Injury.’’ Surgical Laparoscopy, Endoscopy
and Percutaneous Techniques 14 (August 2004): 181–
185.
ORGANIZATIONS

possible complication, particularly for ITP patients.
Infection immediately following surgery may also
occur.

Normal results
Results depend on the reason for the operation. In
blood disorders, the splenectomy will remove the
cause of the blood cell destruction. Normal results
for patients with an enlarged spleen are relief of pain
and of the complications of splenomegaly. It is not
always possible, however, to predict which patients
will respond well or to what degree.
GALE ENCYCLOPEDIA OF MEDICINE

Leukaemia Research Fund. 43 Great Ormond Street,
London, WC1N 3JJ. (020) 7405-0101. <http://dspace.dial.pipex.com/lrf-//>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.
OTHER

‘‘Laparoscopic Splenectomy.’’ Foxhall Surgical Page.
<http://www.foxhall.com/lap_sple.htm>.
Non-emergency Surgery Hotline. (800) 638-6833.

Teresa Odle
Rebecca J. Frey, PhD
3505

Splenectomy

Resources

KEY TERMS

Splenic trauma

Splenic trauma
Definition
Splenic trauma is physical injury to the spleen, the
lymphatic organ located in the upper left side of the
abdomen just under the rib cage. The spleen weighs
between 75 and 150 grams (between 0.16 and 0.33
pounds) in adults.

Description
The spleen is an organ that produces white blood
cells, filters the blood (10–15% of the total blood
supply every minute), stores red blood cells and platelets, and destroys those that are aging. It is located
near the stomach on the left side of the abdomen. A
direct blow to the abdomen may bruise, tear or shatter
the spleen. Trauma to the spleen can cause varying
degrees of damage, the major problem associated with
internal bleeding. Mild splenic subcapsular hematomas are injuries in which bleeding is limited to small
areas on and immediately around the spleen. Splenic
contusions refer to bruising and bleeding on and
around larger areas of the spleen. Lacerations (tears)
are the most common splenic trauma injuries. Tears
tend to occur on the areas between the three main
blood vessels of the spleen. Because of the abundant
blood supply, splenic trauma may cause serious internal bleeding. Most injuries to the spleen in children
heal spontaneously. Severe trauma can cause the
spleen or its blood vessels to rupture or fragment.
Splenic trauma is more common in children than in
adults. In general, children are prone to abdominal injuries due to accidents and falls and because their abdominal organs are less protected by bone, muscle and fat.
Abdominal injuries including splenic trauma are the
most common cause of preventable deaths in children.

Causes and symptoms
The most common cause of injury to the spleen is
blunt abdominal trauma. Blunt trauma is often caused
by a direct blow to the belly, car and motorcycle
accidents, falls, sports mishaps, and fights. The spleen
is the most commonly injured organ in blunt abdominal trauma; splenic injury occurs in nearly 25% of
injuries of this type. Penetrating injuries such as those
from stabbing, gunshot wounds, and accidental impaling also account for cases of splenic trauma, although
far less frequently than blunt trauma.
In adults, ruptured spleens may have been preceded by conditions causing rapid splenic
3506

enlargement, such as infections, particularly those
caused by the Epstein-Barr virus (EBV); cancer;
immune system disorders; diseases of the spleen; or
circulatory problems. In a very few cases the spleen
may be injured by a spell of violent coughing. This
type of rupture is known as an atraumatic rupture.
A spleen that has become enlarged and fragile
from disease is sometimes ruptured by a doctor or
medical student in the course of palpating (feeling)
the patient’s abdomen, or damaged by a surgeon in
the course of an operation on other abdominal organs.
Damage to the spleen may cause localized or general abdominal pain, tenderness, and swelling.
Fractured ribs may be present. Splenic trauma may
cause mild or severe internal bleeding, leading to shock
and for which symptoms include rapid heartbeat,
shortness of breath, thirst, pale or clammy skin, weak
pulse, low blood pressure, dizziness, fainting, sweating.
Vomiting blood, blood in the stools or urine, deterioration of vital signs, and loss of consciousness are other
symptoms.

Diagnosis
The goal of diagnosis of all abdominal traumas is
to detect and treat life-threatening injuries as quickly
as possible. The physician will determine the extent of
organ damage and whether surgery will be necessary
while providing appropriate emergency care. Initial
diagnosis consists of detailing all circumstances of
the injury from the patient and bystanders as well as
the close physical examination of the patient and measurement of vital signs. Blood tests, urinalysis, stool
samples and x rays of the chest and abdomen are
usually performed. Plain x rays may show abdominal
air pockets that indicate internal ruptures, but are
rarely helpful because they do not show splenic and
intra-abdominal damage.
Several other diagnostic tests may be used for the
noninvasive and accurate assessment of splenic
damage: computed tomography scans (CT), of magnetic resonance imaging (MRI), radionuclide scanning,
and ultrasonography. Ultrasonography—particularly
focused abdominal sonographic technique (FAST)—
has now become a standard bedside technique in many
hospitals to check for bleeding in the abdomen.
Imaging tests allow doctors to determine the necessity
and type of surgery required. The CT scan has been
shown to be the most available and accurate test for
abdominal trauma. MRI tests are accurate but costly
and less available in some hospitals, while radionuclide scanning requires more time and patient stability.
Peritoneal lavage is another diagnostic technique in
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Not long ago nearly all cases of splenic trauma
were treated by laparoscopy, opening the abdomen,
and by splenectomy, the surgical removal of the spleen.
This approach resulted from the difficulty in assessing
the severity of the injury, the potential dangers of
shock and death, and the beliefs that the spleen healed
poorly and that it was not an important organ.
Nowadays, improved techniques of diagnosis and
monitoring (particularly the introduction of CT
scans), as well as understanding that removal of the
spleen creates future risk of a lowered capacity to fight
infection has modified treatment approaches.
Research over the past two decades has shown that
the spleen has high healing potential, and confirmed
that children are more susceptible to infection after
splenectomy (post splenectomy sepsis, PSS). PSS has a
mortality rate of over 50% and standard procedure
now avoids splenectomy as much as possible. Adult
splenic trauma is treated by splenectomy more often
than children’s; for unknown reasons, the adult spleen
more frequently spontaneously ruptures after injury.
Adults are also less susceptible to PSS.
Nonoperative treatment
In nonoperative therapy, splenic trauma patients
are monitored closely, often in intensive care units for
several days. Fluid and blood levels are observed and
maintained by intravenous fluid and possible blood
transfusions. Follow-up scans may be used to observe
the healing process.
Operative treatment
Splenic trauma patients require surgery when
nonoperative treatment fails, when major or prolonged internal bleeding exists and for gunshot and
many stab wounds. Whenever possible, surgeons try
to preserve at least part of the spleen and try to repair
its blood vessels.

Prognosis
The ample blood supply to the spleen can promote
rapid healing. Studies have shown that intra-abdominal bleeding associated with splenic trauma stops
without surgical intervention in up to two out of
three cases in children. When trauma patients stabilize
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Computed tomography (CT) scan—Computeraided x-ray examination that allows cross-sectional
views of organs and tissues.
Laparoscope—An optical or fiberoptic instrument
that is inserted by incision in the abdominal wall
and is used to view the interior of the peritoneal
cavity.
Laparoscopy—Procedure using a laparoscope to
view organs, obtain tissue samples and perform
surgery.
Magnetic resonance imaging (MRI)—Imaging
technique using magnets and radio waves to provide internal pictures of the body.
Radionuclide scanning—Diagnostic test in which a
radioactive dye is injected into the bloodstream
and photographed to display internal vessels,
organs and tissues.
Ultrasonography—Imaging test using sound waves
to view internal organs and tissues.

during nonoperative therapy, chances are high that
surgery will be avoided and that spleen injuries will
heal themselves. Splenic trauma patients undergoing
diagnostic tests such as CT and MRI scans have
improved chances of avoiding splenectomy and retaining whole or partial spleens.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Splenic Rupture.’’ Section 11, Chapter 141 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Bjerke, H. Scott, MD, and Janet S. Bjerke, MSN. ‘‘Splenic
Rupture.’’ eMedicine June 19, 2002. <http://www.emedicine.com/med/topic2792.htm>.
Dixon, E., J. S. Graham, R. Sutherland, and P. C. Mitchell.
‘‘Splenic Injury Following Endoscopic Retrograde
Cholangiopancreatography: A Case Report and
Review of the Literature.’’ Journal of the Society of
Laparoendoscopic Surgeons 8 (July-September 2004):
275–277.
Kara, E., Y. Kaya, R. Zeybek, et al. ‘‘A Case of a
Diaphragmatic Rupture Complicated with Lacerations
of Stomach and Spleen Caused by a Violent Cough
Presenting with Mediastinal Shift.’’ Annals of the
Academy of Medicine, Singapore 33 (September 2004):
649–650.
3507

Splenic trauma

which the abdominal cavity is entered and flushed to
check for bleeding. When patients exhibit shock, infection, or prolonged internal bleeding, exploratory
laparoscopy is used for emergency diagnosis.

Sporotrichosis

Laseter, T., and T. McReynolds. ‘‘Spontaneous Splenic
Rupture.’’ Military Medicine 169 (August 2004):
673–674.
ORGANIZATIONS

American Trauma Society. 8903 Presidential Pkwy Suite
512, Upper Marlboro, MD 20227. (800) 556-7890.
<http://www.amtrauma.org>.
OTHER

American Association for the Surgery of Trauma home
page. <http://www.aast.org>.

Douglas Dupler, MA
Rebecca J. Frey, PhD

Split personality see Multiple personality
disorder
Spontaneous abortion see Miscarriage
Sporothrix schenckii infection see
Sporotrichosis

Sporotrichosis
Definition
Sporotrichosis is a chronic infection caused by the
microscopic fungus Sporothrix schenckii. The disease
causes ulcers on the skin that are painless but do not
heal, as well as nodules or knots in the lymph channels
near the surface of the body. Infrequently, sporotrichosis affects the lungs, joints, or central nervous system and can cause serious illness.

Description
The fungus that causes sporotrichosis is found in
spagnum moss, soil, and rotting vegetation. Anyone
can get sporotrichosis, but it is most common among
nursery workers, farm laborers, and gardeners handling spagnum moss, roses, or barberry bushes. Cases
have also been reported in workers whose jobs took
them under houses into crawl spaces contaminated
with the fungus. Children who played on baled hay
have also gotten the disease. Sporotrichosis is sometimes called spagnum moss disease or alcoholic rose
gardener’s disease.

Causes and symptoms
The fungus causing sporotrichosis enters the
body through scratches or cuts in the skin.
3508

Therefore, people who handle plants with sharp
thorns or needles, like roses, barberry, or pines, are
more likely to get sporotrichosis. Sporotrichosis is
not passed directly from person to person, so it is
not possible to catch sporotrichosis from another
person who has it.
The first signs of sporotrichosis are painless pink,
red, or purple bumps usually on the finger, hand, or
arm where the fungus entered the body. These bumps
may appear anywhere from one to 12 weeks after
infection, but usually appear within three weeks.
Unlike many other fungal infections sporotrichosis
does not cause fever or any feelings of general ill
health.
The reddish bumps eventually expand and fester,
creating skin ulcers that do not heal. In addition, the
infection often moves to nearby lymph nodes.
Although most cases of sporotrichosis are limited to
the skin and lymph channels, occasionally the joints,
lungs, and central nervous system become infected. In
rare cases, death may result.
People who have weakened immune systems,
either from a disease such as acquired immune deficiency syndrome (AIDS) or leukemia, or as the result
of medications they take (corticosteroids, chemotherapy drugs), are more likely to get sporotrichosis and
are more at risk for the disease to spread to the internal
organs. Alcoholics and people with diabetes mellitus or
a pre-existing lung disease are also more likely to
become infected. Although sporotrichosis is painless,
it is important for people with symptoms to see a
doctor and receive treatment.

Diagnosis
The preferred way to diagnose sporotrichosis is
for a doctor to obtain a sample of fluid from a freshly
opened sore and send it to a laboratory to be cultured.
The procedure is fast and painless. It is possible to
confirm the presence of advanced sporotrichosis
through a blood test or a biopsy. Doctors may also
take a blood sample to perform tests that rule out
other fungal infections or diseases such as tuberculosis
or bacterial osteomyelitis.
Dermatologists and doctors who work with
AIDS patients are more likely to have experience in
diagnosing sporotrichosis. In at least one state, New
York, the laboratory test to confirm this disease is
provided free through the state health department. In
other cases, diagnosis should be covered by health
insurance at the same level as other diagnostic
laboratory tests.
GALE ENCYCLOPEDIA OF MEDICINE

Acidophilus—The bacteria Lactobacillus acidophilus , usually found in yogurt.
Bacterial osteomyelitis—An infection of the bone
or bone marrow that is caused by a bacterium.

Sporotrichosis is a chronic infection caused by the microscopic fungus Sporothrix schenckii. It produces ulcers on
the skin that are painless but do not heal, and nodules or
knots in the lymph channels near the surface of the body.
(Illustration by Electronic Illustrators Group.)

Bifidobacteria—A group of bacteria normally present in the intestine. Commercial supplements are
available.
Corticosteroids—A group of hormones produced
naturally by the adrenal gland or manufactured
synthetically. They are often used to treat inflammation. Examples include cortisone and prednisone.
Lymph channels—The vessels that transport lymph
throughout the body. Lymph is a clear fluid that
contains cells important in forming antibodies that
fight infection.

Treatment
When sporotrichosis is limited to the skin and
lymph system, it is usually treated with a saturated
solution of potassium iodine that the patient dilutes
with water or juice and drinks several times a day. The
iodine solution can only be prescribed by a physician.
This treatment must be continued for many weeks. Skin
ulcers should be treated like any open wound and
covered with a clean bandage to prevent a secondary
bacterial infection. The drug itraconazol (Sporanox),
taken orally, is also available to treat sporotrichosis.
In serious cases of sporotrichosis, when the internal
organs are infected, the preferred treatment is the drug
amphotericin B. Amphotericin B is a strong anti-fungal
drug with potentially severe toxic side effects. It is given
intravenously, so hospitalization is required for treatment. The patient may also receive other drugs to minimize the side effects of the amphotericin B.

Alternative treatment
Alternative treatment for fungal infections focuses
on maintaining general good health and eating a diet low
in dairy products, sugars, including honey and fruit
juice, and foods, such as beer, that contain yeast. This
is complemented by a diet high in raw food.
Supplements of and vitamins C, E, and A, B complex,
and pantothenic acid may also be added to the diet, as
may Lactobacillus acidophilus, bifidobacteria, and garlic
capsules.
Fungicidal herbs such as myrrh (Commiphora
molmol), tea tree oil (Melaleuca spp.), citrus seed
GALE ENCYCLOPEDIA OF MEDICINE

extract, pau d’arco tea, and garlic (Allium sativum)
may also be applied directly to the infected skin.

Prognosis
Most cases of sporotrichosis are confined to the
skin and lymph system. With treatment, skin sores
begin healing in one to two months, but complete recovery often takes six months or more. People who have
AIDS are also more likely to have the fungus spread
throughout the body, causing a life-threatening infection. In people whose bones and joints are infected or
who have pulmonary lesions, surgery may be necessary.

Prevention
Since an opening in the skin is necessary for the
sporotrichosis fungus to enter the body, the best way
to prevent the disease is to avoid accidental scrapes
and cuts on the hands and arms by wearing gloves and
long sleeves while gardening. Washing hands and arms
well after working with roses, barberry, spagnum
moss, and other potential sources of the fungus may
also provide some protection.
Resources
PERIODICALS

Dillon, Gary P., et. al. ‘‘Handyperson’s Hazard: Crawl
Space Sporotrichosis.’’ The Journal of the American
Medical Association 274 (December 6, 1995): 1673+.

Tish Davidson, A.M.
3509

Sporotrichosis

KEY TERMS

Sports injuries

Sports injuries
Definition
Sports injuries result from acute trauma or repetitive stress associated with athletic activities. Sports
injuries can affect bones or soft tissue (ligaments,
muscles, tendons).
Professional dancers are increasingly recognized
as performing athletes, and many of the treatments
and preventive measures utilized in sports medicine
are now applied to dance-related injuries.
It is also important to remember that many types of
injuries that affect athletes may also occur in workers in
certain occupations; for example, many people in the
building trades develop tennis elbow or golfer’s elbow.
The principles of sports medicine can be applied in the
treatment of most common musculoskeletal injuries.

Description
Adults are less likely to suffer sports injuries than
children, whose vulnerability is heightened by immature reflexes, an inability to recognize and evaluate
risks, and underdeveloped coordination.
In 2002, about 20.3 million Americans suffered a
sports injury. Of those, 53% were minor enough to be
self-treated or left untreated. However, about 10 million Americans annually receive medical attention for
their sports-related injuries. That equates to almost 26
per 1,000 people. The highest rate is among children
age five to 14 years old (59.3 per 1,000 people). As
many as 20% of children who play sports get hurt, and
about 25% of their injuries are classified as serious.
Boys aged 12 to 17 are the highest risk group. More
than 775,000 boys and girls under age 14 are treated in
hospital emergency rooms for sports-related injuries.
Injury rates are highest for athletes who participate
in contact sports, but the most serious injuries are associated with individual activities. Between one-half and
two-thirds of childhood sports injuries occur during
practice, or in the course of unorganized athletic activity.
Baseball and softball are the leading causes of
sports-related facial trauma in the United States,
with 68% of these injuries caused by contact with the
ball rather than player-player collision or being hit by
a swung bat.
Types of sports injuries
About 95% of sports injuries are minor soft tissue
traumas.
3510

The most common sports injury is a bruise (contusion). It is caused when blood collects at the site of
an injury and discolors the skin.
Sprains account for one-third of all sports injuries.
A sprain is a partial or complete tear of a ligament, a
strong band of tissue that connects bones to one
another and stabilizes joints.
A strain is a partial or complete tear of:


muscle (tissue composed of cells that enable the body
to move)



tendon (strong connective tissue that links muscles to
bones)

Inflammation of a tendon (tendinitis) and inflammation of one of the fluid-filled sacs that allow tendons to move easily over bones (bursitis) usually result
from minor stresses that repeatedly aggravate the
same part of the body. These conditions often occur
at the same time.
SKELETAL INJURIES. Fractures account for 5–6% of
all sports injuries. The bones of the arms and legs are
most apt to be broken. Sports activities rarely involve
fractures of the spine or skull. The bones of the legs
and feet are most susceptible to stress fractures, which
occur when muscle strains or contractions make bones
bend. Stress fractures are especially common in ballet
dancers, long-distance runners, and in people whose
bones are thin.

Shin splints are characterized by soreness and slight
swelling of the front, inside, and back of the lower leg,
and by sharp pain that develops while exercising and
gradually intensifies. Shin splints are caused by overuse
or by stress fractures that result from the repeated foot
pounding associated with activities such as aerobics,
long-distance running, basketball, and volleyball.
A compartment syndrome is a potentially debilitating condition in which the muscles of the lower leg
grow too large to be contained within membranes that
enclose them. This condition is characterized by numbness and tingling. Untreated compartment syndrome
can result in long-term loss of function.
BRAIN INJURIES. Brain injury is the primary cause
of fatal sports-related injuries. Concussion, which is
also called mild traumatic brain injury or MTBI, can
result from even minor blows to the head. A concussion can cause loss of consciousness and may affect:


balance



comprehension



coordination



hearing
GALE ENCYCLOPEDIA OF MEDICINE

Sports injuries
Chauncy Billups, a guard for the Denver Nuggets, grimaces after spraining his ankle during a game. (AP/Wide World Photos.
Reproduced by permission.)



memory



swelling



vision



weakness

Diagnosis

Causes and symptoms
Common causes of sports injuries include:


athletic equipment that malfunctions or is used
incorrectly



falls



forceful high-speed collisions between players



wear and tear on areas of the body that are continually subjected to stress
Symptoms include:



instability or obvious dislocation of a joint



pain

GALE ENCYCLOPEDIA OF MEDICINE

Symptoms that persist, intensify, or reduce the
athlete’s ability to play without pain should be evaluated by an orthopedic surgeon. Prompt diagnosis
often can prevent minor injuries from becoming
major problems, or causing long-term damage.
An orthopedic surgeon should examine anyone:


who is prevented from playing by severe pain associated with acute injury



whose ability to play has declined due to chronic or
long-term consequences of an injury



whose injury has caused visible deformities in an arm
or leg.
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Sports injuries

The physician will perform a physical examination, ask how the injury occurred, and what symptoms the patient has experienced. X rays and other
imaging studies of bones and soft tissues may be
ordered.
Anyone who has suffered a blow to the head
should be examined immediately, and at five-minute
intervals until normal comprehension has returned.
The initial examination measures the athlete’s:


awareness



concentration



short-term memory
Subsequent evaluations of concussion assess:



dizziness



headache



nausea



visual disturbances

Treatment
Treatment for minor soft tissue injuries generally
consists of:

Prevention
Every child who plans to participate in organized
athletic activity should have a pre-season sports physical. This special examination is performed by a
pediatrician or family physician who:


carefully evaluates the site of any previous injury



may recommend special stretching and strengthening exercises to help growing athletes create and preserve proper muscle and joint interaction



pays special attention to the cardiovascular and skeletal systems.

Telling the physician which sport the athlete
plays will help that physician determine which parts
of the body will be subjected to the most stress.
The physician then will be able to suggest to the
athlete steps to take to minimize the chance of getting
hurt.
Other injury-reducing game plans include:


being in shape



knowing and obeying the rules that regulate the
activity



not playing when tired, ill, or in pain



compressing the injured area with an elastic
bandage



not using steroids, which can improve athletic performance but cause life-threatening problems



elevation





ice

taking good care of athletic equipment and using it
properly



wearing appropriate protective equipment



rest.

Anti-inflammatories, taken by mouth or injected
into the swelling, may be used to treat bursitis. Antiinflammatory medications and exercises to correct
muscle imbalances usually are used to treat tendinitis.
If the athlete keeps stressing inflamed tendons, they
may rupture, and casting or surgery is sometimes
necessary to correct this condition.
Orthopedic surgery may be required to repair serious sprains and strains.
Controlling inflammation as well as restoring normal use and mobility are the goals of treatment for
overuse injuries.
Athletes who have been injured are usually
advised to limit their activities until their injuries
are healed. The physician may suggest special exercises or behavior modifications for athletes who
have had several injuries. Athletes who have been
severely injured may be advised to stop playing
altogether.
3512

On a larger scale, sports injuries are becoming
a public health concern in America. Prevention
efforts include wearing protective devices (such as
bicycle helmets and pads when skating or skateboarding), and educating both children and adults
about safety. Other preventive efforts include
changes in the rules of the game or sport to minimize injuries. For example, wearing goggles will be
mandatory in women’s lacrosse as of 2005 in order
to reverse the rising rate of eye and other facial
injuries in that sport. Research also continues on
improving equipment. For example, thick rubber
insoles can help prevent against repetitive injuries
from running, but scientists recently observed that
they can add to injuries in sports such as soccer,
where athletes need to make quick changes of
direction. On the other hand, recent improvements
in the design and construction of football helmets
have been credited with a significant decline in the
frequency and severity of head injuries among
football players.
GALE ENCYCLOPEDIA OF MEDICINE

Sprains and strains

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Common Sports Injuries.’’ Section 5, Chapter 62 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

Definition
Sprain refers to damage or tearing of ligaments or
a joint capsule. Strain refers to damage or tearing of a
muscle.

PERIODICALS

Bak, M. J., and T. D. Doerr. ‘‘Craniomaxillofacial Fractures
during Recreational Baseball and Softball.’’ Journal of
Oral and Maxillofacial Surgery 62 (October 2004):
1209–1212.
Bernhardt, David T., MD. ‘‘Concussion.’’ eMedicine July 6,
2004. <http://www.emedicine.com/sports/
topic27htm>.
Chaudry, Samena. ‘‘Insoles Help Prevent Sports Injuries..’’
Student BMJ May 2003: 137.
Conne, J.M., J.L. Annest, and J. Gilchrist. ‘‘Sports and
Recreation Related Injury Episodes in the U.S.
Population.’’ Injury Prevention June 2003: 117.
Koutedakis, Y., and A. Jamurtas. ‘‘The Dancer as a
Performing Athlete: Physiological Considerations.’’
Sports Medicine 34, no. 10 (2004): 651–661.
Levy, M. L., B. M. Ozgur, C. Berry, et al. ‘‘Analysis and
Evolution of Head Injury in Football.’’ Neurosurgery
55 (September 2004): 649–655.
Matz, S. O., and G. Nibbelink. ‘‘Injuries in Intercollegiate
Women’s Lacrosse.’’ American Journal of Sports
Medicine 32 (April-May 2004): 608–611.
Rupp, Timothy J., MD, Marian Bednar, MD, and Stephen
Karageanes, DO. ‘‘Facial Fractures.’’ eMedicine
August 29, 2004. <http://www.emedicine.com/sports/
topic33.htm>.
ORGANIZATIONS

American Academy of Orthopedic Surgeons. 6300 North
River Road, Rosemont, IL 60018-4262. (800) 346-2267.
<http://www.aaos.org>.
American Academy of Otolaryngology—Head and Neck
Surgery. One Prince Street, Alexandria, VA 223143357. (703) 836-4444. <http://www.entnet.org>.
American College of Sports Medicine (ACSM). 401 West
Michigan Street, Indianapolis, IN 46202-3233. (317)
637-9200. Fax: (317) 634-7817. <http://
www.acsm.org>.
Institute for Preventative Sports Medicine. P.O. Box 7032,
Ann Arbor, MI 48107 (313) 434-3390. <http://
www.ipsm.org>.

Maureen Haggerty
Teresa G. Odle
Rebecca J. Frey, PhD

Sports vision see Vision training
Spouse abuse see Abuse
GALE ENCYCLOPEDIA OF MEDICINE

Description
When excessive force is applied to a joint, the
ligaments that hold the bones together may be torn
or damaged. This results in a sprain, and its seriousness depends on how badly the ligaments are torn.
Any joint can be sprained, but the most frequently
injured joints are the ankle, knee, and finger.
Strains are tears in the muscle. Sometimes called
pulled muscles, they usually occur because of overexertion or improper lifting techniques. Sprains and
strains are common. Anyone can have them.
Children under age eight are less likely to have
sprains than are older people. Childrens’ ligaments are
tighter, and their bones are more apt to break before a
ligament tears. People who are active in sports suffer
more strains and sprains than less active people.
Repeated sprains in the same joint make the joint
less stable and more prone to future sprains.

Causes and symptoms
There are three grades of sprains. Grade I sprains
are mild injuries where there is no tearing of the ligament, and no joint function is lost, although there may
be tenderness and slight swelling.
Grade II sprains are caused by a partial tear in the
ligament. These sprains are characterized by obvious
swelling, extensive bruising, pain, difficulty bearing
weight, and reduced function of the joint.
Grade III, or third degree, sprains are caused by
complete tearing of the ligament where there is severe
pain, loss of joint function, widespread swelling and
bruising, and the inability to bear weight. These symptoms are similar to those of bone fractures.
Strains can range from mild muscle stiffness to
great soreness. Strains result from overuse of muscles,
improper use of the muscles, or as the result of injury
in another part of the body when the body compensates for pain by altering the way it moves.

Diagnosis
Grade I sprains and mild strains are usually selfdiagnosed. Grade II and III sprains are often seen by a
3513

Sprains and strains

Resources

Sputum culture

KEY TERMS
Ligament—Tough, fibrous connective tissue that
holds bones together at joints.

tears. Until recently, tearing the ligaments of the knee
meant the end to an athlete’s career. Improved surgical
and rehabilitative techniques now offer the possibility
of complete recovery. However, once a joint has been
sprained, it will never be as strong as it was before.

Prevention
physician, who x rays the area to differentiate between
a sprain and a fracture.

Treatment
Grade I sprains and mild strains can be treated at
home. Basic first aid for sprains consists of RICE:
Rest, Ice for 48 hours, Compression (wrapping in an
elastic bandage), and Elevation of the sprain above the
level of the heart. Over-the-counter pain medication
such as acetaminophen (Tylenol) or ibuprofen
(Motrin) can be taken for pain.
In addition to RICE, people with grade II and
grade III sprains in the ankle or knee usually need to
use crutches until the sprains have healed enough to
bear weight. Sometimes, physical therapy or home
exercises are needed to restore the strength and flexibility of the joint.
Grade III sprains are usually immobilized in a cast
for several weeks to see if the sprain heals. Pain medication is prescribed. Surgery may be necessary to relieve
pain and restore function. Athletic people under age 40
are the most likely candidates for surgery, especially
with grade III knee sprains. For complete healing, physical therapy usually will follow surgery.

Alternative treatment
Alternative practitioners endorse RICE and conventional treatments. In addition, nutritional therapists
recommend vitamin C and bioflavonoids to supplement a diet high in whole grains, fresh fruits, and
vegetables. Anti-inflammatories, such as bromelain (a
proteolytic enzyme from pineapples) and tumeric
(Curcuma longa), may also be helpful. The homeopathic remedy arnica (Arnica montana) may be used
initially for a few days, followed by ruta (Ruta graveolens) for joint-related injuries or Rhus toxicodendron
for muscle-related injuries. If surgery is needed, alternative practitioners can recommend pre- and postsurgical therapies that will enhance healing.

Prognosis
Moderate sprains heal within two to four weeks,
but it can take months to recover from severe ligament
3514

Sprains and strains can be prevented by warmingup before exercising, using proper lifting techniques,
wearing properly fitting shoes, and taping or bracing
the joint.
Resources
PERIODICALS

Wexler, Randall K. ‘‘The Injured Ankle.’’ American Family
Physician 57 (February 1, 1998): 474.

Tish Davidson, A.M.

Sputum culture
Definition
Sputum is material coughed up from the lungs and
expectorated (spit out) through the mouth. A sputum
culture is done to find and identify the microorganism
causing an infection of the lower respiratory tract such
as pneumonia (an infection of the lung). If a microorganism is found, more testing is done to determine
which antibiotics will be effective in treating the
infection.

Purpose
A person with a fever and a continuing cough that
produces pus-like material and/or blood may have an
infection of the lower respiratory tract. Infections of
the lungs and bronchial tubes are caused by several
types of microorganisms, including bacteria, fungi
(molds and yeast), and viruses. A chest x ray provides
visual evidence of an infection; a culture can grow the
microorganism causing the infection. The microorganism is grown in the laboratory so it can be identified, and tested for its response to medications, such as
antifungals and antibiotics.

Description
Based on the clinical condition of the patient, the
physician determines what group of microorganism is
GALE ENCYCLOPEDIA OF MEDICINE

of the bacteria and a list of the antibiotics to which
they are sensitive.
Fungal culture
To look for mold or yeast, a fungal culture is
done. The sputum sample is spread on special culture
plates that will encourage the growth of mold and
yeast. Different biochemical tests and stains are used
to identify molds and yeast. Cultures for fungi may
take several weeks.

Bacterial culture
A portion of the sputum is smeared on a microscope slide for a Gram stain. Another portion is
spread over the surface of several different types of
culture plates, and placed in an incubator at body
temperature for one to two days.
A Gram stain is done by staining the slide with
purple and red stains, then examining it under a microscope. Gram staining checks that the specimen does
not contain saliva or material from the mouth. If many
epithelial (skin) cells and few white blood cells are
seen, the specimen is not pure sputum and is not
adequate for culture. Depending on laboratory policy,
the specimen may be rejected and a new specimen
requested. If many white blood cells and bacteria of
one type are seen, this is an early confirmation of
infection. The color of stain picked up by the bacteria
(purple or red), their shape (such as round or rectangular), and their size provide valuable clues as to their
identity and helps the physician predict what antibiotics might work best before the entire test is completed.
Bacteria that stain purple are called gram-positive;
those that stain red are called gram-negative.
During incubation, bacteria present in the sputum
sample multiply and will appear on the plates as visible
colonies. The bacteria are identified by the appearance
of their colonies, by the results of biochemical tests,
and through a Gram stain of part of a colony.

Viral culture
Viruses are a common cause of pneumonia. For a
viral culture, sputum is mixed with commercially-prepared animal cells in a test tube. Characteristic
changes to the cells caused by the growing virus help
identify the virus. The time to complete a viral culture
varies with the type of virus. It may take from several
days to several weeks.
Special procedures
Tuberculosis is caused by a slow-growing bacteria
called Mycobacterium tuberculosis. Because it does not
easily grow using routine culture methods, special
procedures are used to grow and identify this bacteria.
When a sputum sample for tuberculosis first comes
into the laboratory, a small portion of the sputum is
smeared on a microscope slide and stained with a
special stain, called an acid-fast stain. The stained
sputum is examined under a microscope for tuberculosis organisms, which pick-up the stain, making them
visible. This smear is a rapid screen for the organism,
and allows the physician to receive a preliminary
report within 24 hours.

A sensitivity test, also called antibiotic susceptibility test, is also done. The bacteria are tested against
different antibiotics to determine which will treat the
infection by killing the bacteria.

To culture for tuberculosis, portions of the sputum are spread on and placed into special culture
plates and tubes of broth that promote the growth of
the organism. Growth in broth is faster than growth
on culture plates. Instruments are available that can
detect growth in broth, speeding the process even
further. Growth and identification may take two to
four weeks.

The initial result of the Gram stain is available the
same day, or in less than an hour if requested by the
physician. An early report, known as a preliminary
report, is usually available after one day. This report
will tell if any bacteria have been found yet, and if so,
their Gram stain appearance–for example, a gramnegative rod, or a gram-positive cocci. The final
report, usually available in one to three days, includes
complete identification and an estimate of the quantity

Other microorganisms that cause various types of
lower respiratory tract infections also require special
culture procedures to grow and identify. Mycoplasma
pneumonia causes a mild to moderate form of pneumonia, commonly called walking pneumonia;
Bordetella pertussis causes whooping cough;
Legionella pneumophila, Legionnaire’s disease;
Chlamydia pneumoniae, an atypical pneumonia; and
Chlamydia psittaci, parrot fever.

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Sputum culture

likely to be causing the infection, and then orders one
or more specific types of cultures: bacterial, viral, or
fungal (for yeast and molds). For all culture types, the
sputum must be collected into a sterile container. The
sputum specimen must be collected carefully, so that
bacteria that normally live in the mouth and saliva
don’t contaminate the sputum and complicate the
process of identifying the cause of the infectious
agent. Once in the laboratory, each culture type is
handled differently.

Sputum culture

Pneumocystis carinii causes pneumonia in people
with weakened immune systems, such as people with
AIDS. This organism does not grow in culture. Special
stains are done on sputum when pneumonia caused by
this organism is suspected. The diagnosis is based on
the results of these stains, the patient’s symptoms, and
medical history.
Sputum culture is also called sputum culture and
sensitivity.
It is possible that sputum cultures will eventually
be replaced in the diagnosis of tuberculosis by newer
molecular techniques. These advanced methods speed
the diagnostic process as well as improve its accuracy.
As of late 2002, four molecular techniques are increasingly used in laboratories around the world to diagnose TB. They include polymerase chain reaction to
detect mycobacterial DNA in patient specimens;
nucleic acid probes to identify mycobacteria in culture; restriction fragment length polymorphism analysis to compare different strains of TB for
epidemiological studies; and genetic-based susceptibility testing to identify drug-resistant strains of
mycobacteria.

Preparation
The specimen for culture should be collected
before antibiotics are begun. Antibiotics in the person’s system may prevent microorganisms present in
the sputum from growing in culture.
The best time to collect a sputum sample is early in
the morning, before having anything to eat or drink.
The patient should first rinse his or her mouth with
water to decrease mouth bacteria and dilute saliva.
Through a deep cough, the patient must cough up
sputum from within the chest. Taking deep breaths
and lowering the head helps bring up the sputum.
Sputum must not be held in the mouth but immediately spat into a sterile container. For tuberculosis, the
physician may want the patient to collect sputum
samples on three consecutive mornings.
If coughing up sputum is difficult, a health care
worker can have the patient breathe in sterile saline
produced by a nebulizer. This nebulized saline coats
the respiratory tract, loosening the sputum, and making it easier to cough up. Sputum may also be collected
by a physician during a bronchoscopy procedure.
Bronchoscopy, however, is not regarded as a costeffective way of obtaining a useful sample.
If tuberculosis is suspected, collection of sputum
should be carried out in an isolation room, with all
attending healthcare workers wearing masks.
3516

KEY TERMS
Acid-fast stain—A special stain done to microscopically identify the bacteria that cause tuberculosis.
Culture—A laboratory test done to grow and identify microorganisms causing infection.
Gram stain—Microscopic examination of a portion
of a bacterial colony or sample from an infection site
after it has been stained by special stains. Certain
bacteria pick up and retain the purple stain; these
bacteria are called gram-positive. Other bacteria
loose the purple stain and retain the red stain; these
bacteria are called gram-negative. The color of the
bacteria, in addition to their size and shape, provide
clues as to the identity of the bacteria.
Normal flora—The mixture of bacteria normally
found at specific body sites.
Pneumonia—An infection of the lungs.
Sputum—Material coughed up from the lower
respiratory tract and expectorated through the mouth.
Sensitivity test—A test that determines which antibiotics will kill the bacteria that has been isolated
from a culture.

In addition to special precautions in collecting
sputum when tuberculosis is suspected, workers in
hospital laboratories must take extra care to inactivate
unstained smear preparations that may contain M.
tuberculosis. As of 2002, the most effective deactivation technique is the use of a solution of 5% phenol in
ethanol.

Normal results
Sputum from a healthy person would have no
growth on culture. A mixture of microorganisms,
however, normally found in a person’s mouth and
saliva often contaminate the culture. If these microorganisms grow in the culture, they may be reported as
normal flora contamination.

Abnormal results
The presence of bacteria and white blood cells on
the Gram stain and the isolation of a microorganism
from culture, other than normal flora contamination,
is evidence of a lower respiratory tract infection.
Microorganisms commonly isolated from sputum
include: Streptococcus pneumoniae, Haemophilus
GALE ENCYCLOPEDIA OF MEDICINE

Resources

Stanford-Binet intelligence
scales
Definition

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Infectious Diseases Caused by Mycobacteria.’’
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Pneumonia.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Chedore, P., C. Th’ng, D. H. Nolan, et al. ‘‘Method for
Inactivating and Fixing Unstained Smear Preparations
of Mycobacterium tuberculosis for Improved
Laboratory Safety.’’ Journal of Clinical Microbiology 40
(November 2002): 4077–4080.
McWilliams, T., A. U. Wells, A. C. Harrison, et al. ‘‘Induced
Sputum and Bronchoscopy in the Diagnosis of
Pulmonary Tuberculosis.’’ Thorax 57 (December 2002):
1010–1014.
Su, W. J. ‘‘Recent Advances in the Molecular Diagnosis of
Tuberculosis.’’ Journal of Microbiology, Immunology,
and Infection 35 (December 2002): 209–214.
Wattal, C. ‘‘Improving Bacteriological Diagnosis of
Tuberculosis.’’ Indian Journal of Pediatrics 69,
Supplement 1 (November 2002): S11–S19.
ORGANIZATIONS

American Lung Association. 432 Park Avenue South, New
York, NY 10016. (800) LUNG-USA.
<www.lungusa.org>.
National Heart, Lung, and Blood Institute (NHLBI). P. O.
Box 30105, Bethesda, MD 20824-0105. (301) 592-8573.
<www.nhlbi.nih.gov>.

Nancy J. Nordenson
Rebecca J. Frey, PhD

Squam see Skin cancer, non-melanoma
Squint see Strabismus

The Stanford-Binet intelligence scale is a standardized test that assesses intelligence and cognitive abilities in children and adults aged two to 23.

Purpose
The Stanford-Binet intelligence scale is used as a
tool in school placement, in determining the presence
of a learning disability or a developmental delay, and
in tracking intellectual development. In addition, it is
sometimes included in neuropsychological testing to
assess the brain function of individuals with neurological impairments.

Precautions
Although the Stanford-Binet was developed for
children as young as two, examiners should be cautious in using the test to screen very young children for
developmental delays or disabilities. The test cannot
be used to diagnose mental retardation in children aged
three and under, and the scoring design may not detect
developmental problems in preschool-age children.
Intelligence testing requires a clinically trained
examiner. The Stanford-Binet intelligence scale should
be administered and interpreted by a trained professional, preferably a psychologist.

Description
The Stanford-Binet intelligence scale is a direct
descendent of the Binet-Simon scale, the first intelligence scale created in 1905 by psychologist Alfred
Binet and Dr. Theophilus Simon. This revised edition,
released in 1986, was designed with a larger, more
diverse, representative sample to minimize the gender
and racial inequities that had been criticized in earlier
versions of the test.

SSSS see Staphylococcal scalded skin
syndrome

The Stanford-Binet scale tests intelligence across
four areas: verbal reasoning, quantitative reasoning,
abstract/visual reasoning, and short-term memory.
The areas are covered by 15 subtests, including vocabulary, comprehension, verbal absurdities, pattern
analysis, matrices, paper folding and cutting, copying,
quantitative, number series, equation building, memory for sentences, memory for digits, memory for
objects, and bead memory.

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3517

SSPE see Subacute sclerosing
panencephalitis
SSRIs see Selective serotonin reuptake
inhibitors

Stanford-Binet intelligence scales

influenzae, Staphylococcus aureus, Legionella pneumophila, Mycoplasma pneumonia, Klebsiella pneumoniae,
Pseudomonas aeruginosa, Bordetella pertussis, and
Escherichia coli.

Stapedectomy

KEY TERMS
Norms—Normative or mean score for a particular
age group.
Representative sample—A random sample of people that adequately represents the test-taking population in age, gender, race, and socioeconomic
standing.
Standard deviation—A measure of the distribution
of scores around the average (mean). In a normal
distribution, two standard deviations above and
below the mean includes about 95% of all samples.
The Stanford-Binet intelligence scale. (Photo Researchers Inc.
Reproduced by permission.)

All test subjects take an initial vocabulary test,
which along with the subject’s age, determines the
number and level of subtests to be administered.
Total testing time is 45–90 minutes, depending on the
subject’s age and the number of subtests given. Raw
scores are based on the number of items answered, and
are converted into a standard age score corresponding
to age group, similar to an IQ measure.
The 1997 Medicare reimbursement rate for psychological and neuropsychological testing, including
intelligence testing, is $58.35 an hour. Billing time
typically includes test administration, scoring and
interpretation, and reporting. Many insurance plans
cover all or a portion of diagnostic psychological
testing.

Standardization—The process of determining
established norms and procedures for a test to act
as a standard reference point for future test results.
The Stanford-Binet test was standardized on a
national representative sample of 5,000 subjects.

scale’s subtests to discover strengths and weaknesses
and offer recommendations based upon these
findings.
Resources
ORGANIZATIONS

American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.

Paula Anne Ford-Martin

Normal results
The Stanford-Binet is a standardized test, meaning that norms were established during the design
phase of the test by administering the test to a large,
representative sample of the test population. The test
has a mean, or average, standard score of 100 and a
standard deviation of 16 (subtests have a mean of 50
and a standard deviation of 8). The standard deviation
indicates how far above or below the norm the subject’s score is. For example, an eight-year-old is
assessed with the Stanford-Binet scale and achieves a
standard age score of 116. The mean score of 100 is the
average level at which all eight-year-olds in the representative sample performed. This child’s score would
be one standard deviation above that norm.
While standard age scores provide a reference
point for evaluation, they represent an average of a
variety of skill areas. A trained psychologist will evaluate and interpret an individual’s performance on the
3518

Stapedectomy
Definition
Stapedectomy is a surgical procedure in which the
innermost bone (stapes) of the three bones (the stapes,
the incus, and the malleus) of the middle ear is
removed, and replaced with a small plastic tube of
stainless-steel wire (a prosthesis) to improve the movement of sound to the inner ear.

Purpose
A stapedectomy is used to treat progressive hearing loss caused by otosclerosis, a condition in which
spongy bone hardens around the base of the stapes.
This condition fixes the stapes to the opening of the
inner ear, so that the stapes no longer vibrates
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Stapedectomy

properly; therefore, the transmission of sound to the
inner ear is disrupted. Untreated otosclerosis eventually results in total deafness, usually in both ears.

Description
With the patient under local or general anesthesia,
the surgeon opens the ear canal and folds the eardrum
forward. Using an operating microscope, the surgeon
is able to see the structures in detail, and evaluates the
bones of hearing (ossicles) to confirm the diagnosis of
otosclerosis.
Next, the surgeon separates the stapes from the
incus; freed from the stapes, the incus and malleus
bones can now move when pressed. A laser (or other
tiny instrument) vaporizes the tendon and arch of
the stapes bone, which is then removed from the middle ear.
The surgeon then opens the window that joins the
middle ear to the inner ear and acts as the platform for
the stapes bone. The surgeon directs the laser’s beam
at the window to make a tiny opening, and gently clips
the prosthesis to the incus bone. A piece of tissue is
taken from a small incision behind the ear lobe and
used to help seal the hole in the window and around
the prosthesis. The eardrum is then gently replaced
and repaired, and held there by absorbable packing
ointment or a gelatin sponge. The procedure usually
takes about an hour and a half.
Good candidates for the surgery are those who
have a fixed stapes from otosclerosis, and a conductive
hearing loss at least 20 dB. Patients with a severe
hearing loss might still benefit from a stapedectomy,
if only to improve their hearing to the point where a
hearing aid can be of help. The procedure can improve
hearing in more than 90% of cases.

Preparation
Prior to admission to the hospital, the patient will
be given a hearing test to measure the degree of deafness, and a full ear, nose, and throat exam.
Most surgeons prefer to use general anesthesia; in
this case, an injection will be given to the patient
before surgery.

Aftercare
The patient is usually discharged the morning
after surgery. Antibiotics are given up to five days
after surgery to prevent infection; packing and sutures
are removed about a week after surgery.
GALE ENCYCLOPEDIA OF MEDICINE

A human stapes bone (located in middle ear) extracted during
a stapedectomy. (Custom Medical Stock Photo. Reproduced by
permission.)

It is important that the patient not put pressure on
the ear for a few days after surgery. Blowing one’s
nose, lifting heavy objects, swimming underwater, descending rapidly in high-rise elevators, or taking an
airplane flight should be avoided.
Right after surgery, the ear is usually quite sensitive, so the patient should avoid loud noises until the
ear retrains itself to hear sounds properly.
It is extremely important that the patient avoid
getting the ear wet until it has completely healed.
Water in the ear could cause an infection; most seriously, water could enter the middle ear and cause an
infection within the inner ear, which could then lead to
a complete hearing loss. When taking a shower, and
washing the hair, the patient should plug the ear with a
cotton ball or lamb’s wool ball, soaked in Vaseline.
The surgeon should give specific instructions about
when and how this can be done.
Usually, the patient may return to work and normal activities about a week after leaving the hospital,
although if the patient’s job involves heavy lifting,
three weeks of home rest is recommend. Three days
after surgery, the patient may fly in pressurized
aircraft.

Risks
The most serious risk is an increased hearing loss,
which occurs in about one percent of patients. Because
of this risk, a stapedectomy is usually performed on
only one ear at a time.
Less common complications include:


temporary change in taste (due to nerve damage) or
lack of taste
3519

Staphylococcal infections

KEY TERMS
Cochlea—The hearing part of the inner ear. This
snail-shaped structure contains fluid and thousands
of microscopic hair cells tuned to various frequencies, in addition to the organ of Corti (the receptor
for hearing).
Conductive hearing loss—A type of medically treatable hearing loss in which the inner ear is usually
normal, but there are specific problems in the middle or outer ears that prevent sound from getting to
the inner ear in a normal way.
Incus—The middle of the three bones of the middle
ear. It is also known as the ‘‘anvil.’’

patients usually expect. About half the patients who
had ringing in the ears (tinnitus) before surgery will
have significant relief within six weeks after the
procedure.
Resources
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria VA 223143357. (703) 836-4444. <http://www.entnet.org>.
Better Hearing Institute. 515 King Street, Suite 420,
Alexandria, VA 22314. (703) 684-3391.

Carol A. Turkington

Malleus—One of the three bones of the middle ear.
It is also known as the ‘‘hammer.’’
Ossicles—The three small bones of the middle ear:
the malleus (hammer), the incus (anvil) and the
stapes (stirrup). These bones help carry sound
from the eardrum to the inner ear.
Vertigo—A feeling of dizziness together with a sensation of movement and a feeling of rotating in space.



perforated eardrum



vertigo that may persist and require surgery



damage to the chain of three small bones attached to
the eardrum



temporary facial nerve paralysis



ringing in the ears

Severe dizziness or vertigo may be a signal that
there has been an incomplete seal between the fluids of
the middle and inner ear. If this is the case, the patient
needs immediate bed rest, an exam by the ear surgeon,
and (rarely) an operation to reopen the eardrum to
check the prosthesis.

Normal results
Most patients are slightly dizzy for the first day or
two after surgery, and may have a slight headache.
Hearing improves once the swelling subsides, the
slight bleeding behind the ear drum dries up, and the
packing is absorbed or removed, usually within two
weeks. Hearing continues to get better over the next
three months.
About 90% of patients will have a completely
successful surgery, with markedly improved hearing.
In 8% of cases, hearing improves, but not quite as
3520

Staphylococcal infections
Definition
Staphylococcal (staph) infections are communicable conditions caused by certain bacteria and generally characterized by the formation of abscesses. They
are the leading cause of primary infections originating
in hospitals (nosocomial infections) in the United
States.

Description
Classified since the early twentienth century as
among the deadliest of all disease-causing organisms,
staph exists on the skin or inside the nostrils of 20–
30% of healthy people. It is sometimes found in breast
tissue, the mouth, and the genital, urinary, and upper
respiratory tracts.
Although staph bacteria are usually harmless,
when injury or a break in the skin enables the organisms to invade the body and overcome the body’s
natural defenses, consequences can range from minor
discomfort to death. Infection is most apt to occur in:


newborns



women who are breastfeeding



individuals whose immune systems have been undermined by radiation treatments, chemotherapy, or
medication



intravenous drug users



those with surgical incisions, skin disorders, and serious illness like cancer, diabetes, and lung disease
GALE ENCYCLOPEDIA OF MEDICINE

Staph infections produce pus-filled pockets
(abscesses) located just beneath the surface of the
skin or deep within the body. Risk of infection is
greatest among the very young and the very old.
A localized staph infection is confined to a ring of
dead and dying white blood cells and bacteria. The
skin above it feels warm to the touch. Most of these
abscesses eventually burst, and pus that leaks onto the
skin can cause new infections.
A small fraction of localized staph infections enter
the bloodstream and spread through the body. In
children, these systemic (affecting the whole body) or
disseminated infections frequently affect the ends of
the long bones of the arms or legs, causing a bone
infection called osteomyelitis. When adults develop
invasive staph infections, bacteria are most apt to
cause abscesses of the brain, heart, kidneys, liver,
lungs, or spleen.
Staphylococcus aureus
Named for the golden color of the bacteria grown
under laboratory conditions, S. aureus is a hardy
organism that can survive in extreme temperatures or
other inhospitable circumstances. About 70–90% of
the population carry this strain of staph in the nostrils
at some time. Although present on the skin of only 5–
20% of healthy people, as many as 40% carry it elsewhere, such as in the throat, vagina, or rectum, for
varying periods of time, from hours to years, without
developing symptoms or becoming ill.
S. aureus flourishes in hospitals, where it infects
healthcare personnel and patients who have had surgery; who have acute dermatitis, insulin-dependent
diabetes, or dialysis-dependent kidney disease; or
who receive frequent allergy-desensitization injections. Staph bacteria can also contaminate bedclothes,
catheters, and other objects.
S. aureus causes a variety of infections. Boils and
inflammation of the skin surrounding a hair shaft
(folliculitis) are the most common. Toxic shock (TSS)
and scalded skin syndrome (SSSS) are among the most
serious.
TOXIC SHOCK. Toxic shock syndrome is a lifethreatening infection characterized by severe headache, sore throat, fever as high as 1058F, and a sunburn-like rash that spreads from the face to the rest of
the body. Symptoms appear suddenly; they also
include dehydration and watery diarrhea.

Inadequate blood flow to peripheral parts of the
body (shock) and loss of consciousness occur within
GALE ENCYCLOPEDIA OF MEDICINE

the first 48 hours. Between the third and seventh day
of illness, skin peels from the palms of the hands, soles
of the feet, and other parts of the body. Kidney, liver,
and muscle damage often occur.
SCALDED SKIN SYNDROME. Rare in adults and
most common in newborns and other children under
the age of five, scalded skin syndrome originates with a
localized skin infection. A mild fever and/or an
increase in the number of infection-fighting white
blood cells may occur.

A bright red rash spreads from the face to other
parts of the body and eventually forms scales. Large,
soft blisters develop at the site of infection and elsewhere. When they burst, they expose inflamed skin
that looks as if it had been burned.
MISCELLANEOUS INFECTIONS. S. aureus can also

cause:


arthritis



bacteria in the bloodstream (bacteremia)



pockets of infection and pus under the skin
(carbuncles)



tissue inflammation that spreads below the skin,
causing pain and swelling (cellulitis)



inflammation of the valves and walls of the heart
(endocarditis)



inflammation of tissue that enclosed and protects the
spinal cord and brain (meningitis)



inflammation of
(osteomyelitis)



pneumonia

bone

and

bone

marrow

Other strains of staph
S. EPIDERMIDIS. Capable of clinging to tubing (as
in that used for intravenous feeding, etc.), prosthetic
devices, and other non-living surfaces, S. epidermidis
is the organism that most often contaminates devices
that provide direct access to the bloodstream.

The primary cause of bacteremia in hospital
patients, this strain of staph is most likely to infect
cancer patients, whose immune systems have been
compromised, and high-risk newborns receiving intravenous supplements.
S. epidermidis also accounts for two of every five
cases of prosthetic valve endocarditis. Prosthetic
valve endocarditis is endocarditis as a complication
of the implantation of an artificial valve in the heart.
Although contamination usually occurs during
surgery, symptoms of infection may not become
evident until a year after the operation. More than
3521

Staphylococcal infections

Types of infections

Staphylococcal infections

Causes and symptoms
Staph bacteria can spread through the air, but
infection is almost always the result of direct contact
with open sores or body fluids contaminated by these
organisms.
Staph bacteria often enter the body through
inflamed hair follicles or oil glands. Or they penetrate
skin damaged by burns, cuts and scrapes, infection,
insect bites, or wounds.

A close-up of a woman’s finger and nail cuticle infected
with Staphyloccus aureus. (Custom Medical Stock Photo.
Reproduced by permission.)

Multiplying beneath the skin, bacteria infect and
destroy tissue in the area where they entered the body.
Staph infection of the blood (staphylococcal bacteremia) develops when bacteria from a local infection
infiltrate the lymph glands and bloodstream. These
infections, which can usually be traced to contaminated catheters or intravenous devices, usually cause
persistent high fever. They may cause shock. They also
can cause death within a short time.
Warning signs
Common symptoms of staph infection include:


pain or swelling around a cut, or an area of skin that
has been scraped



boils or other skin abscesses



blistering, peeling, or scaling of the skin; this is most
common in infants and young children



enlarged lymph nodes in the neck, armpits, or groin
A family physician should be notified whenever:

A micrographic image of Staphylococcus aureus. (Photograph
by Oliver Meckes, Photo Researchers, Inc. Reproduced by
permission.)



Lymph nodes in the neck, armpits, or groin become
swollen or tender.



An area of skin that has been cut or scraped becomes
painful or swollen, feels hot, or produces pus. These
symptoms may mean the infection has spread to the
bloodstream.



A boil or carbuncle appears on any part of the face or
spine. Staph infections affecting these areas can
spread to the brain or spinal cord.



A boil becomes very sore. Usually a sign that infection has spread, this condition may be accompanied
by fever, chills, and red streaks radiating from the
site of the original infection.



Boils that develop repeatedly. This type of recurrent
infection could be a symptom of diabetes.

half of the patients who develop prosthetic valve
endocarditis die.
STAPHYLOCOCCUS SAPROPHYTICUS. Existing
within and around the tube-like structure that carries
urine from the bladder (urethra) of about 5% of
healthy males and females, S. saprophyticus is the
second most common cause of unobstructed urinary
tract infections (UTIs) in sexually active young
women. This strain of staph is responsible for 10–
20% of infections affecting healthy outpatients.

3522

Diagnosis
Blood tests that show unusually high concentrations of white blood cells can suggest staph infection,
but diagnosis is based on laboratory analysis of
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Abscess—A cavity containing pus surrounded by
inflamed tissue.
Endocarditis—Inflammation of the lining of the
heart, and/or the heart valves, caused by infection.
Nosocomial infections—Infections that were not
present before the patient came to a hospital, but
were acquired by a patient while in the hospital.

Treatment
Superficial staph infections can generally be cured
by keeping the area clean, using soaps that leave a
germ-killing film on the skin, and applying warm,
moist compresses to the affected area for 20–30 minutes three or four times a day.
Severe or recurrent infections may require a seven
to 10 day course of treatment with penicillin or other
oral antibiotics. The location of the infection and the
identity of the causal bacteria determines which of
several effective medications should be prescribed.
In case of a more serious infection, antibiotics
may be administered intravenously for as long as six
weeks. Intravenous antibiotics are also used to treat
staph infections around the eyes or on other parts of
the face.

goldenseal may be taken internally when symptoms
of infection first appear. Skin infections can be treated by making a paste of water and powdered goldenseal root and applying it directly to the affected
area. The preparation should be covered with a clean
bandage and left in place overnight.


Echinacea (Echinacea spp.). Taken internally, this
herb is believed to have antibiotic properties and is
also thought to strengthen the immune system.



Thyme (Thymus vulgaris), lavender (Lavandula officinalis), or bergamot (Citrus bergamot) oils. These
oils are believed to have antibacterial properties
and may help to prevent the scarring that may result
from skin infections. A few drops of these oils are
added to water and then a compress soaked in the
water is applied to the affected area.



Tea tree oil (Melaleuca spp.). Another infectionfighting herb, this oil can be applied directly to a
boil or other skin infection.

Surgery may be required to drain or remove
abscesses that form on internal organs, or on shunts
or other devices implanted inside the body.

Alternative treatment
Alternative therapies for staph infection are
meant to strengthen the immune system and prevent
recurrences. Among the therapies believed to be helpful for the person with a staph infection are yoga (to
stimulate the immune system and promote relaxation), acupuncture (to draw heat away from the infection), and herbal remedies. Herbs that may help the
body overcome, or withstand, staph infection include:


Garlic (Allium sativum). This herb is believed to have
anitbacterial properties. Herbalists recommend consuming three garlic cloves or three garlic oil capsules
a day, starting when symptoms of infection first
appear.

Prognosis
Most healthy people who develop staph infections
recover fully within a short time. Others develop
repeated infections. Some become seriously ill, requiring long-term therapy or emergency care. A small
percentage die.

Prevention



Cleavers (Galium aparine). This anti-inflammatory
herb is believed to support the lymphatic system. It
may be taken internally to help heal staph abscesses
and reduce swelling of the lymph nodes. A cleavers
compress can also be applied directly to a skin
infection.

Healthcare providers and patients should always
wash their hands thoroughly with warm water and
soap after treating a staph infection or touching an
open wound or the pus it produces. Pus that oozes
onto the skin from the site of an infection should be
removed immediately. This affected area should then
be cleansed with antiseptic or with antibacterial soap.



Goldenseal (Hydrastis canadensis). Another herb
believed to fight infection and reduce imflammation,

To prevent infection from spreading from one
part of the body to another, it is important to shower

GALE ENCYCLOPEDIA OF MEDICINE

3523

Staphylococcal infections

material removed from pus-filled sores, and on analysis of normally uninfected body fluids, such as, blood
and urine. Also, x rays can enable doctors to locate
internal abscesses and estimate the severity of infection. Needle biopsy (removing tissue with a needle,
then examining it under a microscope) may be used
to assess bone involvement.

Staphylococcal scalded skin syndrome

rather than bathe during the healing process. Because
staph infection is easily transmitted from one member
of a household to others, towels, washcloths, and bed
linens used by someone with a staph infection should
not be used by anyone else. They should be changed
daily until symptoms disappear, and laundered separately in hot water with bleach.
Children should frequently be reminded not to
share:


brushes, combs, or hair accessories



caps



clothing



sleeping bags



sports equipment



other personal items

SSSS primarily strikes children under the age of
five, particularly infants. Clusters of SSSS cases (epidemics) can occur in newborn nurseries, when staff in
those nurseries accidentally pass the causative bacteria
between patients. It can also strike other age groups
who have weakened immune systems. Such immunocompromised patients include those with kidney disease, people undergoing cancerchemotherapy, organ
transplant patients, and individuals with acquired
immunodeficiency syndrome (AIDS).

Causes and symptoms

A diet rich in green, yellow, and orange vegetables
can bolster natural immunity. A doctor or nutritionist
may recommend vitamins or mineral supplements to
compensate for specific dietary deficiencies. Drinking
eight to 10 glasses of water a day can help flush disease-causing organisms from the body.
Because some strains of staph bacteria are known
to contaminate artificial limbs, prosthetic devices
implanted within the body, and tubes used to administer medication or drain fluids from the body, catheters and other devices should be removed on a regular
basis, if possible, and examined for microscopic signs
of staph. Symptoms may not become evident until
many months after contamination has occurred, so
this practice should be followed even with patients
who show no sign of infection.
Resources
BOOKS

Civetta, Joseph M., et al., editors. Critical Care.
Philadelphia: Lippincott-Raven Publishers, 1997.

Maureen Haggerty

Staphylococcal scalded skin
syndrome
Definition
Staphylococcal scalded skin syndrome (SSSS) is a
disease, caused by a type of bacteria, in which large
sheets of skin may peel away.
3524

Description

SSSS is caused by a type of bacteria called
Staphylococcus aureus. This bacteria produces a chemical called an epidermolytic toxin (‘‘epiderm,’’ deriving
from the Greek words epi, meaning on, and derma,
meaning skin, refers to the top layer of skin; ‘‘-lytic,’’
deriving from the Greek word lysis, which literally
denotes the act of undoing, means breaking or destroying; a toxin is a poison). While the bacteria itself is not
spread throughout the body, it affects all of the skin by
sending this toxin through the bloodstream.
SSSS begins with a small area of infection. In newborn babies, this may appear as a crusted area around
the umbilicus, or in the diaper area. In children between
the ages of one and six, a small, red, crusty bump
appears near the nose or ear. The child may have no
energy, and may have a fever. The skin becomes sensitive and uncomfortable even before the rash is fully
visible. The rash starts out as bright red patches around
the original area of crusting. Blisters may appear, and
the skin may look wrinkled. When the blisters pop, they
leave pitted areas. Even gently touching these red
patches of skin may cause them to peel away in jagged
sheets. The skin below is shiny, moist, and bright pink.
Within a day or two, the top layer of skin all over the
body is peeling off in large sheets.
The dangers of this illness include the chance that
a different kind of bacteria will invade through the
open areas in the skin and cause a serious systemic
infection (sepsis). A lot of body fluid is lost as the skin
peels away, and the layer underneath dries.
Dehydration is a danger at this point.

Diagnosis
Although good patient care includes taking specimens of blister fluid and smears from the nose or
throat, no bacteria are usually demonstrated. SSSS is
usually diagnosed on the basis of the typical progression of symptoms in a child of this age, prone to this
GALE ENCYCLOPEDIA OF MEDICINE

Starvation
Definition

Epidermis—The top layer of skin.
Epidermolytic—Damaging to the top layer of skin.
Sepsis—An overwhelming infection affecting all
the systems of the body.

Starvation

KEY TERMS

Starvation is the result of a severe or total lack of
nutrients needed for the maintenance of life.

Description
disorder. A sample of skin (skin biopsy) should be
taken, prepared, and examined under a microscope. If
the patient’s disease is truly SSSS, the biopsy will show
a characteristic appearance. There will be no accumulation of those cells usually present in the case of a bacterial infection. Instead, there will be evidence of
disruption of only the top layer of skin (epidermis).

Treatment
Treatment involves careful attention to avoid the
development of dehydration. A variety of lotions and
creams are available to apply to areas where the epidermis has peeled away. This both soothes the sensitive areas, and protects against drying and further
moisture loss.

Prognosis
Most patients heal from SSSS within about 10–14
days. Healing occurs without scarring in the majority
of patients. Death may occur if severe dehydration or
sepsis complicate the illness. About 3% of children die
of these complications; about 50% of immunocompromised adults die of these complications.

Adequate nutrition has two components, necessary nutrients and energy in the form of calories. It is
possible to ingest enough energy without a wellbalanced selection of individual nutrients and produce
diseases that are noticeably different from those resulting from an overall insufficiency of nutrients and
energy. Although all foods are a source of energy for
the human body, it is possible to consume a seemingly
adequate amount of food without getting the required
minimum of energy (calories). For example, marasmus is the result of a diet that is deficient mainly in
energy. Children who get enough calories, but not
enough protein have kwashiorkor. This is typical in
cultures with a limited variety of foods that eat mostly
a single staple carbohydrate like maize or rice. These
conditions overlap and are associated with multiple
vitamin and mineral deficits, most of which have specific names and set of problems associated with them.


Marasmus produces a very skinny child with stunted
growth.



Children with kwashiorkor have body fat, an enlarged
liver, and edema—swelling from excess water in the
tissues. They also have growth retardation.



Niacin deficiency produces pellagra characterized by
diarrhea, skin rashes, brain dysfunction, tongue,
mouth and vaginal irritation, and trouble swallowing.



Thiamine (Vitamin B1) deficiency causes beriberi,
which can appear as heart failure and edema, a
brain and nerve disease, or both.



Riboflavin deficiency causes a sore mouth and
throat, a skin rash, and anemia.



Lack of vitamin C (ascorbic acid)—scurvy—causes
hair damage, bleeding under the skin, in muscles and
joints, gum disease, poor wound healing, and in
severe cases convulsions, fever, loss of blood pressure, and death.



Vitamin B12 is needed to keep the nervous system
working properly. It and pyridoxine (vitamin B6) are
both necessary for blood formation.



Vitamin A deficiency causes at first loss of night
vision and eventually blindness from destruction of
the cornea, a disease called keratomalacia.

Prevention
As always, good hygiene can prevent the passage
of the causative bacteria between people. In the event
of an outbreak in a newborn nursery, members of the
staff should have nasal smears taken to identify an
adult who may be unknowingly carrying the bacteria
and passing it on to the babies.
Resources
BOOKS

Deresiewicz, Robert L., and Jeffrey Parsonnet. In Harrison’s
Principles of Internal Medicine, edited by Anthony S.
Fauci, et al. New York: McGraw-Hill, 1997.

Rosalyn Carson-DeWitt, MD

Staphylococccal food poisoning see Food
poisoning
GALE ENCYCLOPEDIA OF MEDICINE

3525

Starvation



Vitamin K is necessary for blood clotting.



Vitamin D regulates calcium balance. Without it,
children get rickets and adults get osteomalacia.

Causes and symptoms
Starvation may result from a number of factors.
They include:


anorexia nervosa, which is an eating disorder characterized by extreme calorie restriction



intentional fasting



coma



stroke



inability to obtain food (famine; child abuse; aftermath of war or other disaster; being lost in wilderness
or desert areas)



severe gastrointestinal disease

Since the body will combat malnutrition by breaking down its own fat and eventually its own tissue, a
whole host of symptoms can appear. The body’s structure, as well as its functions, are affected. Starved
adults may lose as much as 50% of their normal
body weight.
Characteristic symptoms of starvation include:


shrinkage of such vital organs as the heart, lungs,
ovaries, or testes, and gradual loss of their functions



chronic diarrhea



anemia



reduction in muscle mass and consequent weakness



lowered body temperature combined with extreme
sensitivity to cold



decreased ability to digest food because of lack of
digestive acid production



irritability and difficulty with mental concentration



immune deficiency



swelling from fluid under the skin



decreased sex drive

Complete starvation in adults leads to death
within eight to 12 weeks. In the final stages of starvation, adult humans experience a variety of neurological and psychiatric symptoms, including hallucinations
and convulsions, as well as severe muscle pain and
disturbances in heart rhythm.
In children, chronic malnutrition is marked by
growth retardation. Anemia is the first sign to appear
in an adult. Swelling of the legs is next, due to a drop in
the protein content of the blood. Loss of resistance to
3526

KEY TERMS
Anemia—Not enough red blood cells in the blood.
Anorexia nervosa—Eating disorder marked by malnutrition and weight loss commonly occurring in
young women.
Cornea—The clear part of the front of the eye that
admits light.
Kwashiorkor—Severe malnutritution in children
caused by mainly by a protein-poor diet, characterized by growth retardation.
Marasmus—Severe malnutritution in children
caused by a diet lacking mainly in calories. Can
also be caused by disease and parasitic infection.

infection follows next, along with poor wound healing.
There is also progressive weakness and difficulty swallowing, which may lead to inhaling food. At the same
time, the signs of specific nutrient deficiencies may
appear.

Treatment
If the degree of malnutrition is severe, the intestines may not tolerate a fully balanced diet. They may,
in fact, not be able to absorb adequate nutrition at all.
Carefully prepared elemental diets or intravenous
feeding must begin the treatment. A formula consisting of 42% dried skim milk, 32% edible oil, and 25%
sucrose plus electrolyte, mineral, and vitamin supplements is recommended for the first phase of refeeding.
The treatment back to health is long and first begins
with liquids. Gradually, solid foods are introduced
and a daily diet providing 5,000 calories or more is
instituted.

Prognosis
People can recover from severe degrees of starvation to a normal stature and function. Children, however, may suffer from permanent mental retardation or
growth defects if their deprivation was long and
extreme.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Starvation.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
GALE ENCYCLOPEDIA OF MEDICINE

Btaiche, I. F., and N. Khalidi. ‘‘Metabolic Complications of
Parenteral Nutrition in Adults, Part 1.’’ American
Journal of Health-System Pharmacy 61 (September 15,
2004): 1938–1949.
Nagao, M., Y. Maeno, H. Koyama, et al. ‘‘Estimation of
Caloric Deficit in a Fatal Case of Starvation Resulting
from Child Neglect.’’ Journal of Forensic Science 49
(September 2004): 1073–1076.

J. Ricker Polsdorfer, MD
Rebecca J. Frey, PhD

Stasis dermatitis see Dermatitis
Static encephalopathy see Cerebral palsy
STDs see Sexually transmitted diseases
Steatosis see Fatty liver
Steele-Richardson-Olszewski syndrome see
Progressive supranuclear palsy
Stein-Leventhal syndrome see Polycystic
ovary syndrome
Steinert’s disease see Myotonic dystrophy
Stem cell therapy see Bone marrow
transplantation

Stem cell transplantation
Definition
Stem cells are basic human cells that reproduce
(replicate) easily, providing a continuous source of
new, sometimes different types of cells. A stem cell
transplant is a procedure that replaces unhealthy
stem cells with healthy ones.

Purpose
Physicians use stem cell transplants to treat many
diseases that damage or destroy bone marrow, found
in the soft fatty tissue inside the bones. Examples of
these diseases are leukemia and multiple myeloma.
Some patients lack bone marrow because of aggressive
cancer treatments or diseases such as aplastic anemia,
which causes abnormal blood cell production.
Recent advances in stem cell research have made it
a treatment possibility for patients with certain types
of lymphomas, genetic disorders, and autoimmune
disorders as well. Researchers are hoping to eventually
GALE ENCYCLOPEDIA OF MEDICINE

harvest stem cells to treat diseases such as Parkinson’s
disease, type 1 diabetes, Alzheimer’s disease, liver
disease, arthritis, and spinal cord injuries.

Precautions
The physician will weigh many factors when
determining if a patient is a candidate for stem cell
transplantation, including overall health and function
of many vital organ systems. Stem cell transplantation
is an aggressive treatment and may not be recommended for some patients, including those with
heart, kidney, or lung disorders. If the patient has an
aggressive cancer that has spread throughout the
body, he or she may not be considered for a stem cell
transplant. It once was thought that stem cell transplants were not safe in patients over age 60, but new
research shows that elderly patients can safely receive
stem cells from donors.
Many ethical and legal factors are impacting the
research and development into stem cell transplantation. Much debate surrounds scientific advances. For
example, human embryos, fetal tissues and umbilical
cords are sources of stem cells that may be transplanted or used for disease research. Some people
have ethical problems with the use of embryos in
fertility clinics for stem cell research or transplantation. Some link stem cell transplantation for disease
with cloning and want to stop funding for stem cell
research over fear of human cloning. A study released
in 2005 stated that 63% of Americans back embryonic
stem cell research and 70% support federal legislation
to promote more research. Meanwhile, scientists continue to develop new and exciting possibilities for
transplanting stem cells into the human body that
may one day lead to new treatments for previously
incurable diseases. Many do so with private funding.

Description
Stem cell transplants sometimes are called bone
marrow transplants. Nearly 100 years ago, physicians
tried to give patients with leukemia and anemia bone
marrow by mouth. These treatments were not successful, but led to experiments showing healthy bone marrow transfused into the blood stream could restore
damaged bone marrow.
Today, two types of stem cell transplants are performed most often. When a patient’s own stem cells
are collected (harvested) before they are destroyed by
high-dose chemotherapy or radiation therapy treatments, then returned to the same patient’s body, it is
called an autologous transplant. Using stem cells from
another person, or a donor, is called allogenic
3527

Stem cell transplantation

PERIODICALS

Stem cell transplantation

transplant. In many cases, donor cells come from a
relative, such as a brother or sister. However, the likelihood that a sibling will match the patient is only
about 25%. Stem cells may need to come from a
person not related to the recipient.
To find out if a patient could receive stem cells
from a donor, physicians developed human leukocyte
antigen (HLA) testing to match tissue types. The next
challenge became finding donors. Throughout the
1980s and 1990s, private individuals, hospitals, foundations, and states worked to set up a nationwide
registry of bone marrow donors. The National
Marrow Donor Program (NMDP) now has the largest
stem cell donor registry in the world. In July 2003,
more than five million volunteer donors and more
than 28,000 units of umbilical cord blood were listed
on the NMDP registry. More than 16,000 bone marrow transplants have been performed since the NMDP
was founded in 1986.
Stem cell transplants normally take place at specialized centers. Donor cells are taken from the donor
in an operating room while the patient is unconscious
and under general anesthesia. Bone marrow normally
is harvested from the top of the hip bone. The marrow
usually is filtered, treated, and either transplanted
immediately or frozen for later use. Stem cells are
transfused through an intravenous (IV) catheter that
physicians insert in the patient’s neck or chest.
Physicians refer to this step as the ‘‘rescue process.’’
The stem cells replace old cells. For example, the
transplanted cells travel to the bone cavities and
begin replacing old bone marrow.

Preparation
Standard preparation involves getting rid of the
remaining disease and damaged cells. The exact process depends on the patient. In many cases, the patient
will receive chemotherapy. Some also receive radiation
therapy. Another goal of preparation is to depress the
immune system. This makes it less likely that the
patient’s body will reject the new stem cells. New
advances have been made that allow some of the
patient’s diseased cells to remain and mix with
the new cells. Immediately before transplantation,
the treating physician and staff will give the patient
special instructions and precautions, depending on his
or her disease and exact procedure.

Aftercare
Stem cells take up to three weeks to begin producing new cells or bone marrow, a process called
3528

KEY TERMS
Catheter—A medical device shaped like a tube that
physicians can insert into vessels, canals, or passageways to more easily inject or withdraw fluids.
Embryo—A developing human from the time of
conception to the end of the eighth week after
conception.
Engraftment—The process of transplanted stem
cells reproducing new cells.

engraftment. Until engraftment is complete, patients
may bleed easily and are at risk for infections. They
may be required to stay in the hospital at least one
week following surgery until blood cell counts reach a
safe level. Once home, patients usually must be closely
monitored, be careful not to risk infection, and may be
anemic and sleep most of the time. They may receive
antibiotics to prevent infection and will receive specific
instructions for care from the transplant center staff.
Most stem cell transplant patients cannot return to
work or normal activities for up to six months following the transplant.

Risks
In addition to the risk of a life-threatening infection following a stem cell transplant, patients receiving
stem cells from donors risk serious complications from
graft-versus-host disease (GVHD). GVHD is caused
when the donor’s cells react against the patient’s
(recipient s) tissue. Sometimes, the patient’s body simply rejects the new cells. Researchers continue to
explore ways to lessen risks of complications following
stem cell transplants. For example, recent studies
recommend a measles vaccination after stem cell transplantation to prevent measles in recipients, who are at
risk because of their low immunity.

Normal results
When bone marrow transplantation is successful, it
prolongs the life of a person who might have otherwise
died from the disease that caused damage to the bone
marrow. People with more siblings have a higher
chance of finding a compatible donor, though successful stem cell transplants also occur with donors who
are not related to the recipients. Patients usually can
return to normal activities within six months to one
year after the transplant.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms

PERIODICALS

Causes

‘‘Allogenic Stem Cell Transplantation Is Safe in
Elderly Patients.’’ Immunotherapy Weekly (Sept. 22,
2004):195.
‘‘More Americans Backing Stem Cell Research, Says
Study.’’ Pharma Marketletter (Feb. 21, 2005).
‘‘Patients Should Receive Measles Vaccine After Stem Cell
Transplantation.’’ Life Science Weekly (Nov. 23,
2004):883.
ORGANIZATIONS

International Myeloma Foundation. 12650 Riverside Drive,
Suite 206. North Hollywood, CA 91607-3421. 800-452CURE. http://www.myeloma.org.
National Marrow Donor Program. Suite 500, 3001
Broadway St. NE, Minneapolis, MN 55413-1753. 800627-7692. http://www.marrow.org.

A number of different disorders can cause stillbirth. They include:


Pre-eclampsia and eclampsia. These are disorders of
late pregnancy characterized by high blood pressure,
fluid retention, and protein in the urine.



Diabetes in the mother.



Hemorrhage.



Abnormalities in the fetus caused by infectious diseases, including syphilis, toxoplasmosis, German
measles (rubella), and influenza.



Severe birth defects, including spina bifida. Birth
defects are responsible for about 20% of stillbirths.



Postmaturity. Postmaturity is a condition in which
the pregnancy has lasted 41 weeks or longer.



Unknown causes. These account for about one-third
of stillbirths.

OTHER

Advances in Stem Cell Transplants: A Primer for Patients.
Web page. National Marrow Donor Program, 2005.
http://www.marrow.org/PATIENT/
advances_stem_cell_transplants_primer_patients.html.

Symptoms
Teresa G. Odle

Sterilization see Tubal ligation; Vasectomy

Stillbirth
Definition
A stillbirth is defined as the death of a fetus at any
time after the twentieth week of pregnancy. Stillbirth is
also referred to as intrauterine fetal death (IUFD).

Description
It is important to distinguish between a stillbirth
and other words that describe the unintentional end
of a pregnancy. A pregnancy that ends before the
twentieth week is called a miscarriage rather than a
stillbirth, even though the death of the fetus is a common cause of miscarriage. After the twentieth week,
the unintended end of a pregnancy is called a stillbirth
if the infant is dead at birth and premature delivery if it
is born alive.
Factors that increase a mother’s risk of stillbirth
include: age over 35, malnutrition, inadequate prenatal
care, smoking, and alcohol or drug abuse.
GALE ENCYCLOPEDIA OF MEDICINE

In most cases the only symptom of stillbirth is that
the mother notices that the baby has stopped moving.
In some cases, the first sign of fetal death is premature
labor. Premature labor is marked by a rush of fluid
from the vagina, caused by the tearing of the membrane around the baby; and by abdominal cramps or
contractions.

Diagnosis
When the mother notices that fetal movement has
stopped, the doctor can use several techniques to evaluate whether the baby has died. The doctor can listen
for the fetal heartbeat with a stethoscope, use Doppler
ultrasound to detect the heartbeat, or give the mother
an electronic fetal nonstress test. In this test, the
mother lies on her back with electronic monitors
attached to her abdomen. The monitors record the
baby’s heart rate, movements, and contractions of
the uterus.

Treatment
Medical
In most cases of intrauterine death, the mother will
go into labor within two weeks of the baby’s death. If
the mother does not go into labor, the doctor will bring
on (induce) labor in order to prevent the risk of hemorrhage. Labor is usually induced by giving the mother a
drug (oxytocin) that cause the uterus to contract.
3529

Stillbirth

Resources

Stockholm syndrome

ORGANIZATIONS

KEY TERMS
Alpha-fetoprotein analysis—A blood test that can
be done after the sixteenth week of pregnancy to
evaluate the possibility of spina bifida and other
birth defects in the fetus.
Electronic fetal nonstress test—A test in which
electronic monitors attached to the mother’s abdomen to detect contractions of the uterus as well as
the baby’s heartbeat and movements.
Miscarriage—The spontaneous end of a pregnancy
before the twentieth week. The death of the fetus is
a common cause of miscarriage.
Oxytocin—A drug that is given to induce labor in
some cases of stillbirth.
Pre-eclampsia and eclampsia—Disorders of late
pregnancy associated with high blood pressure,
fluid retention, and protein in the urine. They can
cause stillbirth.
Premature delivery—The birth of a live baby when
a pregnancy ends spontaneously after the twentieth
week.

Follow-up therapy
Emotional support from family and friends, selfhelp groups, and counseling by a mental health professional can help bereaved parents cope with their loss.

Prognosis
With the exception of women with diabetes,
women who have a stillbirth have as good a chance
of carrying a future pregnancy to term as women who
are pregnant for the first time.

Prevention
The risk of stillbirth can be lowered to some extent
by good prenatal care and the mother’s avoidance of
exposure to infectious diseases, smoking, alcohol
abuse, or drug consumption. Tests before delivery
(antepartum testing), such as ultrasound, the alphafetoprotein blood test, and the electronic fetal nonstress test, can be used to evaluate the health of the fetus
before there is a stillbirth.
Resources
BOOKS

Johnson, Robert V. Mayo Clinic Complete Book of
Pregnancy and Baby’s First Year. New York: William
Morrow and Co., Inc.
3530

Compassionate Friends. P.O. Box 3696, Oak Brook, IL
60522. (877) 969-0010. <http:www/
compassionatefriends.org>.
GriefNet. P.O. Box 3272, Ann Arbor, MI 48106. <http://
rivendell.org>.
Hannah’s Prayer. P.O. Box 5016, Auburn CA 95604. (775)
852-9202. <http://www.hannah.org>.
M.E.N.D. (Mommies Enduring Neonatal Death). P.O. Box
1007, Coppell, TX 75067. (972) 459-2396; (888) 6956363. <http://www.mend.org/home_index.asp>.
Pregnancy and Infant Loss Support (SHARE). St. Joseph
Health Center, 300 First Capitol Dr., St. Charles,
MO 63301. (800) 821-6819. <http://
www.nationalshareoffice.com/index.html>.

Carol A. Turkington

Stings see Bites and stings

Stockholm syndrome
Definition
Stockholm syndrome refers to a group of psychological symptoms that occur in some persons in a
captive or hostage situation. It has received considerable media publicity in recent years because it has
been used to explain the behavior of such wellknown kidnapping victims as Patty Hearst (1974)
and Elizabeth Smart (2002). The term takes its
name from a bank robbery in Stockholm, Sweden,
in August 1973. The robber took four employees of
the bank (three women and one man) into the vault
with him and kept them hostage for 131 hours. After
the employees were finally released, they appeared to
have formed a paradoxical emotional bond with their
captor; they told reporters that they saw the police as
their enemy rather than the bank robber, and that
they had positive feelings toward the criminal. The
syndrome was first named by Nils Bejerot (1921–
1988), a medical professor who specialized in addiction research and served as a psychiatric consultant to
the Swedish police during the standoff at the bank.
Stockholm syndrome is also known as Survival
Identification Syndrome.

Description
Stockholm syndrome is considered a complex
reaction to a frightening situation, and experts do
not agree completely on all of its characteristic features or on the factors that make some people more
GALE ENCYCLOPEDIA OF MEDICINE

Most experts, however, agree that Stockholm
syndrome has three central characteristics:


The hostages have negative feelings about the police
or other authorities.



The hostages have positive feelings toward their
captor(s).



The captors develop positive feelings toward the
hostages.

Causes & symptoms
Stockholm syndrome does not affect all hostages
(or persons in comparable situations); in fact, a
Federal Bureau of Investigation (FBI) study of over
1200 hostage-taking incidents found that 92% of the
hostages did not develop Stockholm syndrome. FBI
researchers then interviewed flight attendants who had
been taken hostage during airplane hijackings, and
concluded that three factors are necessary for the syndrome to develop:


The crisis situation lasts for several days or longer.



The hostage takers remain in contact with the hostages; that is, the hostages are not placed in a separate
room.



The hostage takers show some kindness toward the
hostages or at least refrain from harming them.
Hostages abused by captors typically feel anger toward
them and do not usually develop the syndrome.

In addition, people who often feel helpless in other
stressful life situations or are willing to do anything in
order to survive seem to be more susceptible to developing Stockholm syndrome if they are taken hostage.
People with Stockholm syndrome report the same
symptoms as those diagnosed with posttraumatic
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Coping—In psychology, a term that refers to a person’s patterns of response to stress. Some patterns of
coping may lower a person’s risk of developing
Stockholm syndrome in a hostage situation.
Flashback—The re-emergence of a traumatic memory as a vivid recollection of sounds, images, and
sensations associated with the trauma. The person
having the flashback typically feels as if they are
reliving the event. Flashbacks were first described
by doctors treating combat veterans of World War I
(1914–1918).
Identification with an aggressor—In psychology,
an unconscious process in which a person adopts
the perspective or behavior patterns of a captor or
abuser. Some researchers consider it a partial
explanation of Stockholm syndrome.
Regression—In psychology, a return to earlier,
usually childish or infantile, patterns of thought or
behavior.
Syndrome—A set of symptoms that occur together.

stress disorder (PTSD): insomnia, nightmares, general
irritability, difficulty concentrating, being easily
startled, feelings of unreality or confusion, inability
to enjoy previously pleasurable experiences, increased
distrust of others, and flashbacks.

Diagnosis
Stockholm syndrome is a descriptive term for a
pattern of coping with a traumatic situation rather
than a diagnostic category. Most psychiatrists would
use the diagnostic criteria for acute stress disorder or
posttraumatic stress disorder when evaluating a person with Stockholm syndrome.

Treatment
Treatment of Stockholm syndrome is the same as
for PTSD, most commonly a combination of medications for short-term sleep disturbances and psychotherapy for the longer-term symptoms.

Prognosis
The prognosis for recovery from Stockholm syndrome is generally good, but the length of treatment
needed depends on several variables. These include the
3531

Stockholm syndrome

susceptible than others to developing it. One reason
for the disagreement is that it would be unethical to
test theories about the syndrome by experimenting on
human beings. The data for understanding the syndrome are derived from actual hostage situations since
1973 that differ considerably from one another in
terms of location, number of people involved, and
time frame. Another source of disagreement concerns
the extent to which the syndrome can be used to
explain other historical phenomena or more commonplace types of abusive relationships. Many researchers
believe that Stockholm syndrome helps to explain
certain behaviors of survivors of World War II concentration camps; members of religious cults; battered
wives; incest survivors; and physically or emotionally
abused children as well as persons taken hostage by
criminals or terrorists.

Stomach cancer

nature of the hostage situation; the length of time the
crisis lasted, and the individual patient’s general
coping style and previous experience(s) of trauma.

OTHER

Carver, Joseph M., PhD. Love and Stockholm Syndrome:
The Mystery of Loving an Abuser. <http://www.drjoecarver.com/stockholm.html>.

Prevention
Prevention of Stockholm syndrome at the level of
the larger society includes further development of crisis intervention skills on the part of law enforcement as
well as strategies to prevent kidnapping or hostagetaking incidents in the first place. Prevention at the
individual level is difficult as of the early 2000s because
researchers have not been able to identify all the
factors that may place some persons at greater risk
than others; in addition, they disagree on the specific
psychological mechanisms involved in Stockholm
syndrome. Some regard the syndrome as a form of
regression (return to childish patterns of thought or
action) while others explain it in terms of emotional
paralysis (‘‘frozen fright’’) or identification with the
aggressor.

Rebecca Frey, PhD

Stomach acid determination see Gastric acid
determination

Stomach cancer
Definition
Stomach cancer (also known as gastric cancer) is a
disease in which the cells forming the inner lining of
the stomach become abnormal and start to divide
uncontrollably, forming a mass called a tumor.

Resources
BOOKS

American Psychiatric Association.Diagnostic and Statistical
Manual of Mental Disorders, 4th edition, text revision.
Washington, DC: American Psychiatric Association,
2000.
Graham, Dee L. R., with Edna I. Rawlings and Roberta K.
Rigsby. Loving to Survive, Chapter 1, ‘‘Love Thine
Enemy: Hostages and Classic Stockholm Syndrome.’’
New York and London: New York University Press,
1994.
Herman, Judith, MD. Trauma and Recovery, 2nd ed.,
revised. New York: Basic Books, 1997. Chapter 4,
‘‘Captivity,’’ is particularly helpful in understanding
Stockholm syndrome.

Description
The stomach is a J-shaped organ that lies in the
left and central portion of the abdomen. The stomach
produces many digestive juices and acids that mix with
food and aid in the process of digestion. There are five
regions of the stomach that doctors refer to when
determining the origin of stomach cancer. These are:


the cardia, area surrounding the cardiac sphincter
which controls movement of food from the esophagus into the stomach,



the fundus, upper expanded area adjacent to the
cardiac region,



the antrum, lower region of the stomach where it
begins to narrow,



the prepyloric, region just before or nearest the
pylorus,



and the pylorus, the terminal region where the stomach joins the small intestine

PERIODICALS

Bejerot, Nils. ‘‘The Six-Day War in Stockholm.’’ New
Scientist 61 (1974): 486–487.
Fuselier, G. Dwayne, PhD. ‘‘Placing the Stockholm
Syndrome in Perspective.’’ FBI Law Enforcement
Bulletin (July 1999): 23–26.
Grady, Denise. ‘‘Experts Look to Stockholm Syndrome on
Why Girl Stayed.’’ International Herald Tribune, 17
March 2003. A newspaper article about the Elizabeth
Smart kidnapping case.
ORGANIZATIONS

American Psychiatric Association. 1400 K Street, NW,
Washington, DC 20005. <www.psych.org>.
Federal Bureau of Investigation (FBI). J. Edgar Hoover
Building, 935 Pennsylvania Avenue, NW, Washington,
DC 20535-0001. (202) 324-3000.
<http://www.fbi.gov>.
3532

Cancer can develop in any of the five sections of
the stomach. Symptoms and outcomes of the disease
will vary depending on the location of the cancer.
Based on previous data from the National Cancer
Institute and the United States Census, the American
Cancer Society estimates that 21,700 Americans will
be diagnosed with stomach cancer during 2001 and
approximately 13,000 deaths will result from the disease. In most areas, men are affected by stomach
cancer nearly twice as often as women. Most cases of
stomach cancer are diagnosed between the ages of 50
GALE ENCYCLOPEDIA OF MEDICINE

(lymphomas or mucosa-associated lymphoid tissue
[MALT]) in the stomach.

Stomach cancer is one of the leading causes of
cancer deaths in several areas of the world, most notably Japan and other Asian countries. In Japan it
appears almost ten times as frequently as in the
United States. The number of new stomach cancer
cases is decreasing in some areas, however, especially
in developed countries. In the United States, incidence
rates have dropped from 30 individuals per 100,000 in
the 1930s, to only 8 in 100,000 individuals developing
stomach cancer by the 1980s. The use of refrigerated
foods and increased consumption of fresh fruits and
vegetables, instead of preserved foods with high salt
content, may be a reason for the decline.

Another risk factor is the development of polyps,
benign growths in the lining of the stomach. Although
polyps are not cancerous, some may have the potential
to turn cancerous. People in blood group A are also at
elevated risk for this cancer for unknown reasons.
Other speculative causes of stomach cancer include
previous stomach surgery for ulcers or other conditions, or a form of anemia known as pernicious anemia.

Causes and symptoms
While the exact cause for stomach cancer has not
been identified, several potential factors have lead to
increased numbers of individuals developing the disease and therefore, significant risk has been associated. Diet, work environment, exposure to the
bacterium Helicobacter pylori, and a history of stomach disorders such as ulcers or polyps are some of
these believed causes.
Studies have shown that eating foods with high
quantities of salt and nitrites increases the risk of
stomach cancer. The diet in a specific region can
have a great impact on its residents. Making changes
to the types of foods consumed has been shown to
decrease likelihood of disease, even for individuals
from countries with higher risk. For example,
Japanese people who move to the United States or
Europe and change the types of foods they eat have a
far lower chance of developing the disease than do
Japanese people who remain in Japan and do not
change their dietary habits. Eating recommended
amounts of fruit and vegetables may lower a person’s
chances of developing this cancer.
A high risk for developing stomach cancers has
been linked to certain industries as well. The best
proven association is between stomach cancer and
persons who work in coal mining and those who
work processing timber, nickel, and rubber. An unusually large number of these workers have been diagnosed with this form of cancer.
Several studies have identified a bacterium
(Helicobacter pylori) that causes stomach ulcers
(inflammation in the inner lining of the stomach).
Chronic (long-term) infection of the stomach with
these bacteria may lead to a particular type of cancer
GALE ENCYCLOPEDIA OF MEDICINE

Stomach cancer is a slow-growing cancer. It may
be years before the tumor grows very large and produces distinct symptoms. In the early stages of the
disease, the patient may only have mild discomfort,
indigestion, heartburn, a bloated feeling after eating,
and mild nausea. In the advanced stages, a patient will
have loss of appetite and resultant weight loss, stomach pains, vomiting, difficulty in swallowing, and
blood in the stool. Stomach cancer often spreads
(metastasizes) to adjoining organs such as the esophagus, adjacent lymph nodes, liver, or colon.

Diagnosis
Unfortunately, many patients diagnosed with stomach cancer experience pain for two or three years
before informing a doctor of their symptoms. When
a doctor suspects stomach cancer from the symptoms
described by the patient, a complete medical history
will be taken to check for any risk factors. A thorough
physical examination will be conducted to assess all the
symptoms. Laboratory tests may be ordered to check
for blood in the stool (fecal occult blood test) and
anemia (low red blood cell count), which often accompany gastric cancer.
In some countries, such as Japan, it is appropriate
for patients to be given routine screening examinations
for stomach cancer, as the risk of developing cancer in
that society is very high. Such screening might be
useful for all high-risk populations. Due to the low
prevalence of stomach cancer in the United States,
routine screening is usually not recommended unless
a family history of the disease exists.
Whether as a screening test or because a doctor
suspects a patient may have symptoms of stomach
cancer, endoscopy or barium x rays are used in diagnosing stomach cancer. For a barium x ray of the
upper gastrointestinal tract, the patient is given a
chalky, white solution of barium sulfate to drink.
This solution coats the esophagus, the stomach, and
the small intestine. Air may be pumped into the stomach after the barium solution in order to get a clearer
3533

Stomach cancer

and 70, but in families with a hereditary risk of stomach cancer, younger cases are more frequently seen.

Stomach cancer

picture. Multiple x rays are then taken. The barium
coating helps to identify any abnormalities in the lining of the stomach.
In another more frequently used test, known as
upper gastrointestinal endoscopy, a thin, flexible,
lighted tube (endoscope) is passed down the patient’s
throat and into the stomach. The doctor can view the
lining of the esophagus and the stomach through the
tube. Sometimes, a small ultrasound probe is attached
at the end of the endoscope. This probe sends high
frequency sound waves that bounce off the stomach
wall. A computer creates an image of the stomach wall
by translating the pattern of echoes generated by the
reflected sound waves. This procedure is known as an
endoscopic ultrasound or EUS.
Endoscopy has several advantages, in that the
physician is able to see any abnormalities directly. In
addition, if any suspicious-looking patches are seen,
biopsy forceps can be passed painlessly through the
tube to collect some tissue for microscopic examination. This is known as a biopsy. EUS is beneficial
because it can provide valuable information on depth
of tumor invasion.
After stomach cancer has been diagnosed and
before treatment starts, another type of x-ray scan is
taken. Computed tomography (CT) is an imaging
procedure that produces a three-dimensional picture
of organs or structures inside the body. CT scans are
used to obtain additional information in regard to
how large the tumor is and what parts of the stomach
it borders; whether the cancer has spread to the lymph
nodes; and whether it has spread to distant parts of the
body (metastasized), such as the liver, lung, or bone. A
CT scan of the chest, abdomen, and pelvis is taken. If
the tumor has gone through the wall of the stomach
and extends to the liver, pancreas, or spleen, the CT
will often show this. Although a CT scan is an effective
way of evaluating whether cancer has spread to some
of the lymph nodes, it is less effective than EUS in
evaluating whether the nodes closest to the stomach
are free of cancer. However, CT scans, like barium xrays, have the advantage of being less invasive than
upper endoscopy.
Laparoscopy is another procedure used to stage
some patients with stomach cancer. This involves a
medical device similar to an endoscope. A laparoscopy
is a minimally invasive surgery technique with one or a
few small incisions, which can be performed on an
outpatient basis, followed by rapid recovery. Patients
who may receive radiation therapy or chemotherapy
before surgery may undergo a laparoscopic procedure
to determine the precise stage of cancer. The patient
3534

with bone pain or with certain laboratory results
should be given a bone scan.
Benign gastric neoplasms are tumors of the stomach that cause no major harm. One of the most
common is called a submucosal leiomyoma. If a leiomyoma starts to bleed, surgery should be performed to
remove it. However, many leiomyomas require no
treatment. Diagnosis of stomach cancers should be
conducted carefully so that if the tumor does not
require treatment the patient is not subjected to a
surgical operation.

Treatment
More than 95% of stomach cancers are caused by
adenocarcinomas, malignant cancers that originate
in glandular tissues. The remaining 5% of stomach
cancers include lymphomas and other types of cancers. It is important that gastric lymphomas be accurately diagnosed because these cancers have a much
better prognosis than stomach adenocarcinomas.
Approximately half of the people with gastric lymphomas survive five years after diagnosis. Treatment for
gastric lymphoma involves surgery combined with
chemotherapy and radiation therapy.
Staging of stomach cancer is based on how deep
the growth has penetrated the stomach lining; to
what extent (if any) it has invaded surrounding
lymph nodes; and to what extent (if any) it has
spread to distant parts of the body (metastasized).
The more confined the cancer, the better the chance
for a cure.
One important factor in the staging of adenocarcinoma of the stomach is whether or not the tumor has
invaded the surrounding tissue and, if it has, how deep
it has penetrated. If invasion is limited, prognosis is
favorable. Disease tissue that is more localized
improves the outcome of surgical procedures performed to remove the diseased area of the stomach.
This is called a resection of the stomach.
Several distinct ways of classifying stomach cancer according to cell type have been proposed. The
Lauren classification is encountered most frequently.
According to this classification system, gastric adenocarcinomas are either called intestinal or diffuse.
Intestinal cancers are much like a type of intestinal
cancer called intestinal carcinoma. Intestinal tumors
are more frequently found in males and in older
patients. The prognosis for these tumors is better
than that for diffuse tumors. Diffuse tumors are
more likely to infiltrate, that is, to move into another
organ of the body.
GALE ENCYCLOPEDIA OF MEDICINE

Partial or total gastrectomy is often accompanied
by other surgical procedures. Lymph nodes are frequently removed and nearby organs, or parts of these
organs, may be removed if cancer has spread to them.
Such organs may include the pancreas, colon, or
spleen.
Preliminary studies suggest that patients who
have tumors that cannot be removed by surgery at
the start of therapy may become candidates for surgery later. Combinations of chemotherapy and radiation therapy are sometimes able to reduce disease for
which surgery is not initially appropriate. Preliminary
studies are being performed to determine if some of
these patients can become candidates for surgical procedures after such therapies are applied.
An excised section of a human stomach showing a cancerous tumor (center, triangular shape). (Custom Medical Stock
Photo. Reproduced by permission.)

Because symptoms of stomach cancer are so mild,
treatment often does not commence until the disease is
well advanced. The three standard modes of treatment
for stomach cancer include surgery, radiation therapy,
and chemotherapy. While deciding on the patient’s
treatment plan, the doctor takes into account many
factors. The location of the cancer and its stage are
important considerations. In addition, the patient’s
age, general health status, and personal preferences
are also taken into account.
Surgery
In the early stages of stomach cancer, surgery may
be used to remove the cancer. Surgical removal of
adenocarcinoma is the only treatment capable of eliminating the disease. Laparoscopy is often used before
surgery to investigate whether or not the tumor can be
removed surgically. If the cancer is widespread and
GALE ENCYCLOPEDIA OF MEDICINE

Chemotherapy
Whether or not patients undergoing surgery for
stomach cancer should receive chemotherapy is a controversial issue. Chemotherapy involves administering
anti-cancer drugs either intravenously (through a vein
in the arm) or orally (in the form of pills). This can
either be used as the primary mode of treatment or
after surgery to destroy any cancerous cells that may
have migrated to distant sites. Most cancers of the
gastrointestinal tract do not respond well to chemotherapy, however, adenocarcinoma of the stomach
and advanced stages of cancer are exceptions.
Chemotherapy medicines such as doxorubicin,
mitomycin C, and 5-fluorouracil, used alone, provide
benefit to at least one in five patients. Combinations of
agents may provide even more benefit, although it is
not certain that this includes longer survival. For example, some doctors use what is called the FAM regimen,
which combines 5-fluorouacil, doxorubicin, and mitomycin. Some doctors prefer using 5-fluorouracil alone
to FAM since side effects are more moderate. Another
combination some doctors are using involve high doses
3535

Stomach cancer

cannot be removed with surgery, an attempt will be
made to remove blockage and control symptoms such
as pain or bleeding. Depending on the location of the
cancer, a portion of the stomach may be removed, a
procedure called a partial gastrectomy. In a surgical
procedure known as total gastrectomy, the entire stomach may be removed. However, doctors prefer to
leave at least part of the stomach if possible. Patients
who have been given a partial gastrectomy achieve a
better quality of life than those having a total gastrectomy and typically lead normal lives. Even when the
entire stomach is removed, the patients quickly adjust
to a different eating schedule. This involves eating
small quantities of food more frequently. Highprotein foods are generally recommended.

Stomach cancer

of the medications methotrexate, 5- fluorouracil, and
doxorubicin. Other combinations that have shown benefit include the ELF regimen, a combination of leucovorin, 5- fluorouracil, and etoposide. The EAP regimen,
a combination of etoposide, doxorubicin, and cisplatin
is also used.
Although chemotherapy using a single medicine is
sometimes used, the best response rates are often
achieved with combinations of medicines. Therefore,
in addition to studies exploring the effectiveness of
new medicines there are other studies attempting to
evaluate how to best combine existing forms of chemotherapy to bring the greatest degree of help to
patients.
Radiation therapy
Radiation therapy is often used after surgery to
destroy the cancer cells that may not have been completely removed during surgery. To treat stomach
cancer, external beam radiation therapy is generally
used. In this procedure, high-energy rays from a
machine that is outside of the body are concentrated
on the area of the tumor. In the advanced stages of
gastric cancer, radiation therapy is used to ease symptoms such as pain and bleeding. However, studies of
radiation treatment for stomach cancer have shown
that the way it has been used it has been ineffective for
many patients.
Researchers are actively assessing the role of chemotherapy and radiation therapy used before a surgical procedure is conducted. They are searching for
ways to use both chemotherapy and radiation therapy
so that they increase the length of survival of patients
more effectively than current methods are able to do.

Prognosis
Overall, approximately 20% of patients with stomach cancer live at least five years following diagnosis.
Patients diagnosed with stomach cancer in its early
stages have a far better prognosis than those for
whom it is in the later stages. In the early stages, the
tumor is small, lymph nodes are unaffected, and the
cancer has not migrated to the lungs or the liver.
Unfortunately, only about 20% of patients with stomach cancer are diagnosed before the cancer had
spread to the lymph nodes or formed a distant
metastasis.
It is important to remember that statistics on
prognosis may be misleading. Newer therapies are
being developed rapidly and five-year survival has
not yet been measured with these. Also, the largest
3536

KEY TERMS
Adenocarcinoma—Malignant cancers that originate in the tissues of glands or that form glandular
structures.
Anemia—A condition in which iron levels in the
blood are low.
Barium x ray (upper GI)—An x-ray test of the upper
part of the gastrointestinal (GI) tract (including the
esophagus, stomach, and a small portion of the
small intestine) after the patient is given a white,
chalky barium sulfate solution to drink. This substance coats the upper GI and the x rays reveal any
abnormality in the lining of the stomach and the
upper GI.
Biopsy—Removal of a tissue sample for examination under the microscope to check for cancer
cells.
Chemotherapy—Treatment of cancer with synthetic drugs that destroy the tumor either by inhibiting the growth of the cancerous cells or by killing
the cancer cells.
Endoscopic ultrasound (EUS)—A medical procedure in which sound waves are sent to the stomach wall by an ultrasound probe attached to
the end of an endoscope. The pattern of echoes
generated by the reflected sound waves are translated into an image of the stomach wall by a
computer.
External radiation therapy—Radiation therapy that
focuses high-energy rays from a machine on the
area of the tumor.
Infiltrate—A tumor that moves into another organ
of the body.
Polyp—An abnormal growth that develops on the
inside of a hollow organ such as the colon, stomach, or nose.
Radiation therapy—Treatment using high-energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Total gastrectomy—Surgical removal (excision) of
the entire stomach.
Upper endoscopy—A medical procedure in which
a thin, lighted, flexible tube (endoscope) is
inserted down the patient’s throat. Through this
tube the doctor can view the lining of the esophagus, stomach, and the upper part of the small
intestine.

GALE ENCYCLOPEDIA OF MEDICINE

Stomach flushing
Definition
Stomach flushing is the repeated introduction of
fluids into the stomach through a nasogastric tube, and
their subsequent withdrawal by nasogastric suction.

Prevention
Avoiding many of the risk factors associated with
stomach cancer may prevent its development.
Excessive amounts of salted, smoked, and pickled
foods should be avoided, as should foods high in
nitrates. A diet that includes recommended amounts
of fruits and vegetables is believed to lower the risk
of several cancers, including stomach cancer. The
American Cancer Society recommends eating at least
five servings of fruits and vegetables daily and choosing six servings of food from other plant sources,
such as grains, pasta, beans, cereals, and whole grain
bread.
Abstaining from tobacco and excessive amounts
of alcohol will reduce the risk for many cancers. In
countries where stomach cancer is common, such as
Japan, early detection is important for successful
treatment.

Purpose
Stomach flushing is performed to aid in controlling gastrointestinal bleeding or to cleanse the stomach
of poisons.
Controlling stomach bleeding
Bleeding from the esophagus due to ruptured
veins or bleeding from the stomach due to ulcers is a
medical emergency. In an attempt to stop the bleeding,
the stomach is flushed with large quantities of bodytemperature saline solution or ice water. This procedure is called stomach flushing or gastric lavage.
Stomach flushing to control bleeding is not uniformly accepted, and some experts believe it is of little
benefit and exposes the patient to unnecessary risks. It
is usually done in conjunction with the administration
of drugs to constrict the blood vessels.

Resources
BOOKS

Stomach flushing to remove poisons

Braunwald, Eugene, et al. Harrison’s Principles of Internal
Medicine. 15th ed. New York: McGraw-Hill, 2001.
Herfindal Eric T., and Dick R. Gourley. Textbook of
Therapeutics: Drug and Disease Management. 7th ed.
Philadelphia: Lippincott Williams & Wilkins, 2000.
Humes, H. David, editor. Kelley’s Textbook of Internal
Medicine. Philadelphia: Lippincott Williams & Wilkins,
2000.
Pazdur, Richard, et al. Cancer Management: A
Multidisciplinary Approach: Medical, Surgical, &
Radiation Oncology. 4th ed. Melville, NY: PRR, 2000.
Steen, Grant, and Joseph Mirro. Childhood Cancer: A
Handbook from St. Jude Children’s Research Hospital.
Cambridge, MA: Perseus Publishing, 2000.
ORGANIZATIONS

National Coalition for Cancer Survivorship. 1010 Wayne
Ave., 7th Floor, Silver Spring, MD 20910-5600. (301)
650-9127 or (877) NCCS-YES. <http://
www.cansearch.org>.

Lata Cherath, PhD
Bob Kirsch

Stomach flu see Gastroenteritis
GALE ENCYCLOPEDIA OF MEDICINE

At one time, stomach flushing was common practice to remove certain poisons. Recent thinking by the
American Academy of Clinical Toxicology is that stomach flushing should not be used routinely with poisoned patients. It is useful only if the patient has
swallowed a life-threatening quantity of poison, and
when the flushing can be done within 60 minutes of
having swallowed the poison.

Precautions
In poisoning cases, stomach flushing should not be
used if the poison is a strong corrosive acid (hydrochloric acid, sulfuric acid), alkali (lye, ammonia), or a
volatile hydrocarbon such as gasoline. Stomach flushing should also not be done on patients who are having
convulsions. Patients who are losing or have lost consciousness must have their airways intubated before a
nasogastric tube is inserted.

Description
Stomach flushing is performed in a hospital emergency room or intensive care unit by an emergency
3537

Stomach flushing

group of people diagnosed with stomach cancer are
between 60 and 70 years of age, suggesting that some
of these patients die not from cancer but from other
age-related diseases. As a result, some patients with
stomach cancer may be expected to have longer survival than did patients just ten years ago.

Stomatitis

Resources

KEY TERMS
Electrolytes—Salts and minerals that ionize in
body fluids. Common human electrolytes are
sodium chloride, potassium, calcium, and sodium
bicarbonate. Electrolytes control the fluid balance
of the body and are important in muscle contraction, energy generation, and almost any major
biochemical reaction in the body.
Saline—A salt water solution that mimics the concentration of electrolytes in the blood.

room physician or gastroenterologist. A nasogastric
tube is inserted, and small amounts of saline or ice
water are introduced into the stomach and withdrawn.
The procedure is repeated until the withdrawn fluid is
clear.

Preparation
Little preparation is necessary for this procedure
other than educating the patient as to what will happen. The patient should remove dental appliances
before the nasogastric tube is inserted.

Aftercare
After stomach flushing, the patient’s vital signs
will be monitored. Checks will be made for fluid and
electrolyte imbalances. If necessary, additional treatment to prevent gastrointestinal bleeding or poisoning
will be done.

Risks
In poisoning cases, stomach flushing delays the
administration of activated charcoal, which may be
more beneficial to treating the patient than flushing
the stomach. In addition, stomach flushing may stimulate bleeding from the esophagus or stomach. The
patient may inhale some of the stomach contents,
causing aspiration, pneumonia, or infection in the
lungs. Fluid and electrolyte imbalances are more likely
to occur in older, sicker patients. Mechanical damage
to the throat is more likely in patients who are
uncooperative.

Normal results
Stomach flushing is usually tolerated by patients
and is a temporary treatment, performed in conjunction with other therapies.
3538

PERIODICALS

‘‘Gastric Lavage (The AACT/EAPCCT Position Statements
on Gastrointestinal Decontamination).’’ Journal of
Toxicology: Clinical Toxicology 35, no. 7 (December
1997): 771.

Tish Davidson, A.M.

Stomach removal see Gastrectomy
Stomach resection see Gastrectomy

Stomatitis
Definition
Inflammation of the mucous lining of any of the
structures in the mouth, which may involve the cheeks,
gums, tongue, lips, and roof or floor of the mouth. The
word ‘‘stomatitis’’ literally means inflammation of the
mouth. The inflammation can be caused by conditions
in the mouth itself, such as poor oral hygiene, poorly
fitted dentures, or from mouth burns from hot food or
drinks, or by conditions that affect the entire body,
such as medications, allergic reactions, or infections.

Description
Stomatitis is an inflammation of the lining of any
of the soft-tissue structures of the mouth. Stomatitis is
usually a painful condition, associated with redness,
swelling, and occasional bleeding from the affected
area. Bad breath (halitosis) may also accompany the
condition. Stomatitis affects all age groups, from the
infant to the elderly.

Causes and symptoms
A number of factors can cause stomatitis; it is a
fairly common problem in the general adult population in North America. Poorly fitted oral appliances,
cheek biting, or jagged teeth can persistently irritate
the oral structures. Chronic mouth breathing due to
plugged nasal airways can cause dryness of the mouth
tissues, which in turn leads to irritation. Drinking
beverages that are too hot can burn the mouth, leading
to irritation and pain. Diseases, such as herpetic infections (the common cold sore), gonorrhea, measles, leukemia, AIDS, and lack of vitamin C can present with
oral signs. Other systemic diseases associated with
stomatitis include inflammatory bowel disease (IBD)
GALE ENCYCLOPEDIA OF MEDICINE

Aphthous stomatitis, also known as recurrent
aphthous ulcers (RAU) or canker sores, is a specific
type of stomatitis that presents with shallow, painful
ulcers that are usually located on the lips, cheeks,
gums, or roof or floor of the mouth. These ulcers can
range from pinpoint size to up to 1 in (2.5 cm) or more
in diameter. Though the causes of canker sores are
unknown, nutritional deficiencies, especially of vitamin B12, folate, or iron is suspected. Generalized or
contact stomatitis can result from excessive use of
alcohol, spices, hot food, or tobacco products.
Sensitivity to mouthwashes, toothpastes, and lipstick
can irritate the lining of the mouth. Exposure to heavy
metals, such as mercury, lead, or bismuth can cause
stomatitis. Thrush, a fungal infection, is a type of
stomatitis.

Diagnosis
Diagnosis of stomatitis can be difficult. A
patient’s history may disclose a dietary deficiency, a
systemic disease, or contact with materials causing an
allergic reaction. A physical examination is done to
evaluate the oral lesions and other skin problems.
Blood tests may be done to determine if any infection
is present. Scrapings of the lining of the mouth may be
sent to the laboratory for microscopic evaluation, or
cultures of the mouth may be done to determine if an
infectious agent may be the cause of the problem.

Treatment
The treatment of stomatitis is based on the problem causing it. Local cleansing and good oral hygiene
are fundamental. Sharp-edged foods such as peanuts,
tacos, and potato chips should be avoided. A softbristled toothbrush should be used, and the teeth and
gums should be brushed carefully; the patient should
avoid banging the toothbrush into the gums. Local
factors, such as ill-fitting dental appliances or sharp
teeth, can be corrected by a dentist. An infectious
cause can usually be treated with medication.
Systemic problems, such as AIDS, leukemia, and anemia are treated by the appropriate medical specialist.
Minor mouth burns from hot beverages or hot foods
will usually resolve on their own in a week or so.
Chronic problems with aphthous stomatitis are treated by first correcting any vitamin B12, iron, or folate
deficiencies. If those therapies are unsuccessful,
medication can be prescribed which can be applied to
each aphthous ulcer with a cotton-tipped applicator.
This therapy is successful with a limited number of
GALE ENCYCLOPEDIA OF MEDICINE

Stomatitis

and Behçet’s syndrome, an inflammatory multisystem
disorder of unknown cause.

This patient is afflicted with stomatitis, a common inflammatory disease of the mouth. (Photograph by Edward H. Gill,
Custom Medical Stock Photo. Reproduced by permission.)

patients. More recently, low-power treatment with a
carbon dioxide laser has been found to relieve the
discomfort of recurrent aphthae. Major outbreaks of
aphthous stomatitis can be treated with tetracycline
antibiotics or corticosteroids. Valacyclovir has been
shown to be effective in treating stomatitis caused by
herpesviruses.
Patients may also be given topical anesthetics
(usually a 2% lidocaine gel) to relieve pain and a
protective paste (Orabase) or a coating agent like
Kaopectate to protect eroded areas from further irritation from dentures, braces, or teeth.

Alternative treatment
Alternate treatment of stomatitis mainly involves
prevention of the problem. Patients with such dental
appliances as dentures should visit their dentist on a
regular basis. Patients with systemic diseases or
chronic medical problems need to ask their health
care provider what types of oral problems they can
expect from their particular disease. These patients
must also contact their medical clinic at the first sign
of problems. Common sense needs to be exercised
when consuming hot foods or drinks. Use of tobacco
products should be discouraged. Alcohol should be
used in moderation. Mouthwashes and toothpastes
known to the patient to cause problems should be
avoided.
Botanical medicine can assist in resolving stomatitis. One herb, calendula (Calendula officinalis), in
tincture form (an alcohol-based herbal extract) and
diluted for a mouth rinse, can be quite effective in
treating aphthous stomatitis and other manifestations
of stomatitis.
3539

Stool culture

KEY TERMS
Aphthous stomatitis—A specific type of stomatitis
presenting with shallow, painful ulcers. Also
known as canker sores.
Stomatitis—Inflammation of the lining of the
mouth, gums, or tongue.
Thrush—A form of stomatitis caused by Candida
fungi and characterized by cream-colored or bluish
patches on the tongue, mouth, or pharynx.

More recently, a group of researchers in Brazil
have reported that an extract made from the leaves
of Trichilia glabra, a plant found in South America, is
effective in killing several viruses that cause stomatitis.

Prognosis
The prognosis for the resolution of stomatitis is
based on the cause of the problem. Many local factors
can be modified, treated, or avoided. Infectious causes
of stomatitis can usually be managed with medication,
or, if the problem is being caused by a certain drug, by
changing the offending agent.

Mirowski, Ginat W., DMD, MD, and Christy L. Nebesio.
‘‘Aphthous Stomatitis.’’ eMedicine September 24, 2004.
<http://www.emedicine.com/derm/topic486.htm>.
Sciubba, James J., DMD, PhD. ‘‘Denture Stomatitis.’’
eMedicine June 11, 2002. <http://www.emedicine.com/
derm/topic642.htm>.
Shulman, J. D., M. M. Beach, and F. Rivera-Hidalgo. ‘‘The
Prevalence of Oral Mucosal Lesions in U.S. Adults:
Data from the Third National Health and Nutrition
Examination Survey, 1988–1994.’’ Journal of the
American Dental Association 135 (September 2004):
1279–1286.
Wohlschlaeger, A. ‘‘Prevention and Treatment of Mucositis:
A Guide for Nurses.’’ Journal of Pediatric Oncology
Nursing 21 (September-October 2004): 281–287.
ORGANIZATIONS

American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.
American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://
www.ama-assn.org>.

Joseph Knight, PA
Rebecca J. Frey, PhD

Stone removal see Gallstone removal

Prevention
Stomatitis caused by local irritants can be prevented by good oral hygiene, regular dental checkups,
and good dietary habits. Problems with stomatitis
caused by systemic disease can be minimized by good
oral hygiene and closely following the medical therapy
prescribed by the patient’s health care provider.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disorders of the Oral Region.’’ In The Merck Manual
of Diagnosis and Therapy. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
PERIODICALS

Cella, M., D. A. Riva, F. C. Coulombie, and S. E. Mersich.
‘‘Virucidal Activity Presence in Trichilia glabra
Leaves.’’ Revista Argentina de microbiologia 36
(July-September 2004): 136–138.
Miller, C. S., L. L. Cunningham, J. E. Lindroth, and S. A.
Avdiushko. ‘‘The Efficacy of Valacyclovir in
Preventing Recurrent Herpes Simplex Virus Infections
Associated with Dental Procedures.’’ Journal of the
American Dental Association 135 (September 2004):
1311–1318.

3540

Stool culture
Definition
Stool culture is a test to identify bacteria in
patients with a suspected infection of the digestive
tract. A sample of the patient’s feces is placed in a
special medium where bacteria is then grown. The
bacteria that grow in the culture are identified using
a microscope and biochemical tests.

Purpose
Stool culture is performed to identify bacteria or
other organisms in persons with symptoms of gastrointestinal infection, most commonly diarrhea.
Identification of the organism is necessary to determine the treatment of the patient’s infection or to trace
the cause of an outbreak or epidemic of certain types
of diarrhea.
According to the Centers for Disease Control and
Prevention (CDC), doctors are most likely to order a
stool culture for patients with any of the following
characteristics: AIDS, bloody stools, diarrhea lasting
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Stool culture is performed only if an infection of
the digestive tract is suspected. The test has no harmful
effects.

Description
Stool culture may also be called fecal culture. To
obtain a specimen for culture, the patient is asked to
collect a stool sample into a special sterile container. In
some cases, the container may contain a transport
solution. Specimens may need to be collected on
three consecutive days. It is important to return the
specimen to the doctor’s office or the laboratory in the
time specified by the physician or nurse. Laboratories
do not accept stool specimens contaminated with
water, urine, or other materials.
The culture test involves placing a sample of the
stool on a special substance, called a medium, that
provides nutrients for certain organisms to grow and
reproduce. The medium is usually a thick gel-like substance. The culture is done in a test tube–or on a flat
round culture plate–which is incubated at the proper
temperature for growth of the bacteria. After a colony
of bacteria grows in the medium, the type of bacteria is
identified by observing the colony’s growth, its physical characteristics, and its microscopic features. The
bacteria may be dyed with special stains that make it
easier to identify features specific to particular
bacteria.
The length of time needed to perform a stool
culture depends on the laboratory where it is done
and the culture methods used. Stool culture usually
takes 72 hours or longer to complete. Some organisms
may take several weeks to grow in a culture.
An antibiotic sensitivity test may be done after a
specific bacterium is identified. This test shows which
antibiotics will be most effective for treating the
infection.
Although most intestinal infections are caused by
bacteria, in some cases a fungal or viral culture may be
necessary. The most common bacterial infections of
the digestive tract are caused by Shigella, Salmonella,
Campylobacter, and Yersinia. Patients taking certain
antibiotics may be susceptible to infection with
Clostridium difficile. In some cases, as with
Clostridium difficile, the stool culture is used to detect
the toxin (poison or harmful chemical) produced by
the bacteria.
GALE ENCYCLOPEDIA OF MEDICINE

Patients with AIDS, or other immune system diseases, may also have gastrointestinal infections caused
by such fungi as Candida, or viral organisms including
cytomegalovirus.
Several intestinal parasites may cause gastrointestinal infection and diarrhea. Parasites are not cultured, but are identified microscopically in a test called
‘‘Stool Ova and Parasites.’’
Insurance coverage for stool culture may vary
among different insurance plans. This common test
usually is covered if ordered by a physician approved
by the patient’s insurance plan, and if it is done at an
approved laboratory.

Alternative methods
Newer methods of testing stool samples for specific disease organisms include various forms of polymerase chain reaction (PCR) assays. One type that has
been used to test for several different types of intestinal
viruses at the same time is the RT-PCR, which stands
for reverse transcriptase polymerase chain reaction.
This assay measures changes in an organism’s messenger RNA. RT-PCR assays have several advantages
over standard stool cultures: they require only very
small samples of material; they can be performed
much more rapidly; and they can be used to test environmental water for virus contamination as well as
human stool samples.

Preparation
The physician or other healthcare provider will
ask the patient for a complete medical history and
perform a physical examination to determine possible
causes of the gastrointestinal problem. Information
about the patient’s diet, any medications taken, and
recent travel may provide clues to the identity of possible infectious organisms.
Stool culture normally doesn’t require any special
preparation. Patients do not need to change their diet
before collecting the specimen. Intake of some substances can contaminate the stool specimen and
should not be taken the day before collection. These
substances include castor oil, bismuth, and laxative
preparations containing psyllium hydrophilic
mucilloid.

Normal results
Bacteria that are normally found in the intestines
include Pseudomonas and Escherichia coli. These
enteric bacteria (bacteria of the gastrointestinal
3541

Stool culture

longer than three days, high fever, history of recent
travel abroad, or severe dehydration.

Stool fat test

KEY TERMS
Bismuth—A substance used in medicines to treat
diarrhea, nausea, and indigestion.
Enteric—Pertaining to the intestine.
Enterotoxigenic—Refers to an organism that produces toxins in the gastrointestinal tract that cause
such things as vomiting, diarrhea, and other symptoms of food poisoning.
Feces—Material excreted by the intestines.
Flora—Refers to normal bacteria found in a healthy
person.
Gastrointestinal—Referring to the digestive tract;
the stomach and intestines.
Psyllium hydrophilic mucilloid—A plant material
contained in some laxatives.
Sterile—Free of microorganisms.
Toxin—A poison; usually refers to protein poisons
produced by bacteria, animals, and some plants.

Detection Assay for Use with Conventional, RealTime, and Integrated Cell Culture/RT-PCR.’’ Canadian
Journal of Microbiology 50 (April 2004): 269–278.
Hennessy, T. W., R. Marcus, V. Deneen, et al. ‘‘Survey of
Physician Diagnostic Practices for Patients with Acute
Diarrhea: Clinical and Public Health Implications.’’
Clinical Infectious Diseases 38, Supplement 3 (April 15,
2004): s203–S211.
Heryford, A. G., and S. A. Seys. ‘‘Outbreak of Occupational
Campylobacteriosis Associated with a Pheasant
Farm.’’ Journal of Agricultural Safety and Health 10
(May 2004): 127–132.
Rohayem, J., S. Berger, T. Juretzek, et al. ‘‘A Simple and
Rapid Single-Step Multiplex RT-PCR to Detect
Norovirus, Astrovirus and Adenovirus in Clinical Stool
Samples.’’ Journal of Virological Methods 118 (June 1,
2004): 49–59.
Sloan, L. M., J. R. Uhl, E. A. Vetter, et al. ‘‘Comparison of
the Roche LightCycler vanA/vanB Detection Assay
and Culture for Detection of Vancomycin-Resistant
Enterococci from Perianal Swabs.’’ Journal of Clinical
Microbiology 42 (June 2004): 2636–2643.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Toni Rizzo
Rebecca J. Frey, PhD

system) are considered normal flora and usually do
not cause infection in the digestive tract.

Abnormal results
Bacteria that do not normally inhabit the digestive
tract, and that are known to cause gastrointestinal
infection include Shigella, Salmonella, Campylobacter,
and Yersinia. Clostridium difficile produces a toxin that
can cause severe diarrhea. Other bacteria that produce
toxins are Staphylococcus aureus, Bacillus cereus, and
enterotoxigenic (producing disease in the digestive system) Escherichia coli. Although Escherichia coli is a
normal bacteria found in the intestines, the enterotoxigenic type of this bacteria can be acquired from eating
contaminated meat, juice, or fruits. It produces a toxin
that causes severe inflammation and bleeding of the
colon.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Disturbances in Newborns and Infants.’’ In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Grimm, A. C., J. L. Cashdollar, F. P. Williams, and G. S.
Fout. ‘‘Development of an Astrovirus RT-PCR
3542

Stool fat test
Definition
Stool fats, also known as fecal fats, or fecal lipids,
are fats that are excreted in the feces. When secretions
from the pancreas and liver are adequate, emulsified
dietary fats are almost completely absorbed in the
small intestine. When a malabsorption disorder or
other cause disrupts this process, excretion of fat in
the stool increases.

Purpose
This test evaluates digestion of fats by determining excessive excretion of lipids in patients exhibiting
signs of malabsorption, such as weight loss, abdominal distention, and scaly skin.

Precautions
Drugs that may increase fecal fat levels include
enemas and laxatives, especially mineral oil. Drugs that
GALE ENCYCLOPEDIA OF MEDICINE

Description
Excessive excretion of fecal fat is called steatorrhea, a condition that is suspected when the patient
has large, ‘‘greasy,’’ and foul-smelling stools. Both
digestive and absorptive disorders can cause steatorrhea. Digestive disorders affect the production and
release of the enzyme lipase from the pancreas, or
bile from the liver, which are substances that aid digestion of fats; absorptive disorders disturb the absorptive and enzyme functions of the intestine. Any
condition that causes malabsorption or maldigestion
is also associated with increased fecal fat. As an example, children with cystic fibrosis have mucous plugs
that block the pancreatic ducts. The absence or significant decrease of the pancreatic enzymes, amylase,
lipase, trypsin, and chymotrypsin limits fat protein
and carbohydrate digestion, resulting in steatorrhea
due to fat malabsorption.
Both qualitative and quantitative tests are used to
identify excessive fecal fat. The qualitative test involves
staining a specimen of stool with a special dye, then
examining it microscopically for evidence of malabsorption, such as undigested muscle fiber and various
fats. The quantitative test involves drying and weighing
a 72-hour stool specimen, then using an extraction
technique to separate the fats, which are subsequently
evaporated and weighed. This measurement of the total
output of fecal fat per 24 hours in a three-day specimen
is the most reliable test for steatorrhea.

Preparation
This test requires a 72-hour stool collection. The
patient should abstain from alcohol during this time
and maintain a high-fat diet (100 g/day) for three days
before the test, and during the collection period. The
patient should call the laboratory for instructions on
how to collect the specimen.

determined by measuring the difference between
ingested fat and fecal fat, and expressing that difference
as a percentage. The figure, called the fat retention
coefficient, is 95% or greater in healthy children and
adults. A low value is indicative of steatorrhea.

Abnormal results
Increased fecal fat levels are found in cystic fibrosis, malabsorption secondary to other conditions like
Whipple’s disease or Crohn’s disease, maldigestion
secondary to pancreatic or bile duct obstruction, and
‘‘short-gut’’ syndrome secondary to surgical resection,
bypass, or congenital anomaly.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Stool O & P test
Definition
The stool O & P test is the stool ova and parasites
test. In this test, a stool sample is examined for the
presence of intestinal parasites and their eggs, which
are called ova.

Purpose
The ova and parasites test is performed to look for
and identify intestinal parasites and their eggs in persons with symptoms of gastrointestinal infection.
Patients may have no symptoms, or experience diarrhea, blood in the stools, and other gastrointestinal
distress. Identification of a particular parasite indicates the cause of the patient’s disease and determines
the medication needed to treat it.

Precautions
Normal results
Reference values vary from laboratory to laboratory, but are generally found within the range of 5–7 g/
24 hr.
It should be noted that children, especially infants,
cannot ingest the 100 g/day of fat that is suggested for
the test. Therefore, a fat retention coefficient is
GALE ENCYCLOPEDIA OF MEDICINE

Stool O & P is performed if an infection of the
digestive tract is suspected. The test has no harmful
effects.

Description
Examination of the stool for ova and parasites is
done to diagnose parasitic infection of the intestines.
3543

Stool O & P test

may decrease fecal fat include Metamucil and barium.
Other substances that can affect test results include
alcohol, potassium chloride, calcium carbonate, neomycin, kanamycin, and other broad-spectrum antibiotics.

Stool O & P test

The test may be done in the doctor’s office or a laboratory. The patient collects a stool sample in one or more
sterile containers containing special chemical fixatives.
The feces should be collected directly into the container.
It must not be contaminated with urine, water, or other
materials. Three specimens are often needed–collected
every other day, or every third day. However, as many
as six specimens may be needed to diagnose the amoeba
Entamoeba histolytica. The specimen does not need to
be refrigerated. It should be delivered to the doctor’s
office or laboratory within 12 hours.
In the laboratory, the stool sample is observed for
signs of parasites and their eggs. Some parasites are
large enough to be seen without a microscope. For
others, microscope slides are prepared with fresh
unstained stool, and with stool dyed with special
stains. These preparations are observed with a microscope for the presence of parasites or their eggs.
An unstained stool examination for ova and parasites normally only takes a few minutes. If specimen
staining and other preparation is done, the test may
take longer. When the specimen is sent to a laboratory,
the results may take eight to 24 hours to be reported.
The most common intestinal parasites in North
America that cause infections are:


roundworms: Ascaris lumbricoides



hookworms: Necator americanus



pinworms: Enterobius follicularis



tapeworms: Diphyllobothrium latum, Taenia saginata, and Taenia solium



protozoa: Entamoeba histolytica (an amoeba), and
Giardia lamblia (a flagellate)

Numerous other parasites are found in other parts
of the world. These may be contracted by travelers to
other countries. Patients with acquired immune deficiency syndrome (AIDS) or other immune system disorders are commonly infected with the parasites in the
Microsporidia family, Cryptosporidium, and Isospora
belli.
Insurance coverage for stool ova and parasites
may vary among different insurance plans. This test
usually is covered if ordered by a physician approved
by the patient’s insurance plan, and if it is done at an
approved laboratory.

KEY TERMS
Amoeba—A type of protozoa (one-celled animal)
that can move or change its shape by extending
projections of its cytoplasm.
Bismuth—A substance used in medicines to treat
diarrhea, nausea, and indigestion.
Cryptosporidium—A type of parasitic protozoa.
Feces—Material excreted by the intestines.
Flagellate—A microorganism that uses flagella
(hair-like projections) to move.
Gastrointestinal—Referring to the digestive tract;
the stomach and intestines.
Isospora belli—A type of parasitic protozoa.
Microsporida—A type of parasitic protozoa.
Ova—Eggs.
Parasite—An organism that lives on or inside
another living organism (host), causing damage to
the host.
Pathogenic—Disease-causing.
Protozoa—One-celled
eukaryotic
belonging to the kingdom Protista.

organisms

Sterile—Free of microorganisms.

causes of the gastrointestinal symptoms. Information
about the patient’s diet, any medications taken, and
recent travel may provide clues to the identity of possible infectious parasites.
Collecting a stool sample for ova and parasite
detection normally doesn’t require any special preparation. Patients do not need to change their diet
before collecting the specimen. Patients should avoid
taking any medications or treatments containing
mineral oil, castor oil, or bismuth, magnesium or
other antidiarrheal medicines, or antibiotics for seven
to 10 days before collecting the specimen.

Normal results
Normally, parasites and eggs should not be found
in stools. Some parasites are not pathogenic, which
means they do not cause disease. If these are found, no
treatment is necessary.

Preparation
The physician, or other healthcare provider, will
ask the patient for a complete medical history, and
perform a physical examination to determine possible
3544

Abnormal results
The presence of any pathogenic parasite indicates
an intestinal parasitic infection. Depending on the
GALE ENCYCLOPEDIA OF MEDICINE

Strabismus is equally common in boys and girls. It
sometimes runs in families.

Other types of damage caused by intestinal parasites include anemia due to hemorrhage caused by
hookworms, and anemia caused by depletion of vitamin B12 through the action of tapeworms.

Another common form of strabismus, exotropia,
may only be noticeable when a child looks at far-away
objects, daydreams, or is tired or sick.

When a parasite is identified, the patient can be
treated with the appropriate medications to eliminate
the parasite.
Resources
BOOKS

Zaret, Barry L., et al., editors. The Patient’s Guide to Medical
Tests. Boston: Houghton Mifflin, 1997.

Types of strabismus
Esotropia is the most common type of strabismus
in infants. Accommodative esotropia develops in children under age two who cross their eyes when focusing
on objects nearby. This usually occurs in children who
are moderately to highly farsighted (hyperopic).

Sometimes the eye turn is always in the same eye;
however sometimes the turn alternates from one eye to
the other’.
Most children with strabismus have comitant
strabismus. No matter where they look, the degree of
deviation does not change. In incomitant strabismus,
the amount of misalignment depends upon which
direction the eyes are pointed.
False strabismus (pseudostrabismus)

Toni Rizzo

A child may appear to have a turned eye, however
this appearance may actually be due to:

Stool occult blood test see Fecal occult
blood test
Stool ova and parasites test see Stool O & P
test

Strabismus
Definition
Strabismus is a condition in which the eyes do not
point in the same direction. It can also be referred to as
a tropia or squint.

Description
Strabismus occurs in 2–5% of all children. About
half are born with the condition, which causes one or
both eyes to turn:


inward (esotropia or ‘‘crossed eyes’’)



outward (exotropia or ‘‘wall eyes’’)



upward (hypertropia)



downward (hypotropia)

GALE ENCYCLOPEDIA OF MEDICINE



extra skin that covers the inner corner of the eye



a broad, flat nose



eyes set unusually close together or far apart

This condition, false strabismus, usually disappears as the child’s face grows. An eye doctor needs
to determine whether the eyeturn is true or
pseudostrabismus.
With normal vision, both eyes send the brain the
same message. This binocular fixation (both eyes looking directly at the same object) is necessary to see
three-dimensionally and to aid in depth perception.
When an eye is misaligned, the brain receives two
different images. Young children learn to ignore distorted messages from a misaligned eye, but adults with
strabismus often develop double vision (diplopia).
A baby’s eyes should be straight and parallel by
three or four months of age. A child who develops
strabismus after the age of eight or nine years is said
to have adult-onset strabismus.

Causes and symptoms
Strabismus can be caused by a defect in muscles or
the part of the brain that controls eye movement. It is
especially common in children who have:
3545

Strabismus

parasite identified, other tests may need to be performed to determine if the parasite has invaded other
parts of the body. Some parasites travel from the intestines to other parts of the body and may already have
caused damage to other tissues by the time a diagnosis
is made. For example, the roundworm, Ascaris penetrates the intestinal wall and can cause inflammation in
the abdomen. It can also migrate to the lungs and cause
pneumonia. This kind of injury can occur weeks before
the roundworm eggs show up in the stool.

Strabismus



brain tumors



cerebral palsy



Down syndrome



hydrocephalus



other disorders that affect the brain

Diseases that cause partial or total blindness can
cause strabismus. So can extreme farsightedness, cataracts, eye injury, or having much better vision in one
eye than the other.
In adults, strabismus is usually caused by:


diabetes



head trauma



stroke



brain tumor



other diseases affecting nerves that control eye
muscles

The most obvious symptom of strabismus is an
eye that isn’t always straight. The deviation can vary
from day to day or during the day. People who have
strabismus often squint in bright sunlight or tilt their
heads to focus their eyes.

Diagnosis
Every baby’s eyes should be examined by the age
of six months. A baby whose eyes have not straightened by the age of four months should be examined to
rule out serious disease.
A pediatrician, family doctor, ophthalmologist,
or optometrist licensed to use diagnostic drugs uses
drops that dilate the pupils and temporarily paralyze
eye-focusing muscles to evaluate visual status and
ocular health. Early diagnosis is important. Some eye
turns may be a result of a tumor. Untreated strabismus
can damage vision in the unused eye and possibly
result in lazy eye (amblyopia).

Treatment
Preserving or restoring vision and improving
appearance may involve one or more of the following:

A close-up of ophthalmic surgery being performed to correct
strabismus. (Photograph by Michael English, M.D. Custom
Medical Stock Photo. Reproduced by permission.)



medication injected into an overactive eye muscle to
allow the opposite muscle to straighten the eye



vision training (also called eye exercises)

Prognosis
Early consistent treatment usually improves
vision and appearance. The most satisfactory results
are achieved if the condition is corrected before the age
of seven years old.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Academy of Pediatric Ophthalmology and
Strabismus (AAPOS). <http://med-aapos.bu.edu>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.

Maureen Haggerty



glasses to aid in focusing and straighten the eye(s)



patching to force infants and young children to use
and straighten the weaker eye

Strawberry marks see Birthmarks



eye drops or ointments as a substitute for patching or
glasses, or to make glasses more effective

Strep culture see Throat culture



surgery to tighten, relax, or reposition eye muscles

3546

Strengthening exercises see Exercise
Strep test see Streptococcal antibody tests
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Streptococcal sore throat, or strep throat as it is
more commonly called, is an infection of the mucous
membranes lining the pharynx. Sometimes the tonsils
are also infected (tonsillitis). The disease is caused by
group A Streptococcus bacteria. Untreated strep
throat may develop into rheumatic fever or other serious conditions.

Description
Strep throat accounts for between 5–10% of all sore
throats. Although anyone can get strep throat, it is most
common in school-age children. People who smoke,
who are fatigued, run down, or who live in damp,
crowded conditions are also more likely to become
infected. Children under age two and adults who are
not around children are less likely to get the disease.
Strep throat occurs most frequently from
November to April. The disease passes directly from
person to person by coughing, sneezing, and close contact. Very occasionally the disease is passed through
food, when a food handler infected with strep throat
accidentally contaminates food by coughing or sneezing. Statistically, if someone in the household is
infected, one out of every four other household members may get strep throat within two to seven days.

Causes and symptoms
A person with strep throat suddenly develops a
painful sore throat one to five days after being exposed
to the streptococcus bacteria. The pain is indistinguishable from sore throats caused by other diseases.
The infected person usually feels tired and has a
fever, sometimes accompanied by chills, headache,
muscle aches, swollen lymph glands, and nausea.
Young children may complain of abdominal pain.
The tonsils look swollen and are bright red, with
white or yellow patches of pus on them. Sometimes
the roof of the mouth is red or has small red spots.
Often a person with strep throat has bad breath.
Despite these common symptoms, strep throat
can be deceptive. It is possible to have the disease
and not show any of these symptoms. Many young
children complain only of a headache and stomachache, without the characteristic sore throat.
Occasionally, within a few days of developing the
sore throat, an individual may develop a fine, rough,
sunburn-like rash over the face and upper body, and
GALE ENCYCLOPEDIA OF MEDICINE

Untreated strep throat can cause rheumatic fever.
This is a serious illness, although it occurs rarely. The
most recent outbreak appeared in the United States in
the mid-1980s. Rheumatic fever occurs most often in
children between the ages of five and 15, and may have
a genetic component, since it seems to run in families.
Although the strep throat that causes rheumatic fever
is contagious, rheumatic fever itself is not.
Rheumatic fever begins one to six weeks after an
untreated streptococcal infection. The joints, especially the wrists, elbows, knees, and ankles become
red, sore, and swollen. The infected person develops
a high fever, and possibly a rapid heartbeat when lying
down, paleness, shortness of breath, and fluid retention. A red rash over the trunk may come and go for
weeks or months. An acute attack of rheumatic fever
lasts about three months.
Rheumatic fever can cause permanent damage to
the heart and heart valves. It can be prevented by
promptly treating streptococcal infections with antibiotics. It does not occur if all the streptococcus bacteria
are killed within the first 10–12 days after infection.
In the 1990s, outbreaks of a virulent strain of
group A Streptococcus were reported to cause a
toxic-shock-like illness and a severe invasive infection
called necrotizing fasciitis, which destroys skin and
muscle tissue. Although these diseases are caused by
group A Streptococci, they rarely begin with strep
throat. Usually the streptococcus bacteria enters the
body through a skin wound. These complications are
rare. However, since the death rate in necrotizing fasciitis is 30–50%, it is wise to seek prompt treatment for
any streptococcal infection.

Diagnosis
Diagnosis of a strep throat by a doctor begins with
a physical examination of the throat and chest. The
doctor will also look for signs of other illness, such as
a sinus infection or bronchitis, and seek information
about whether the patient has been around other people
with strep throat. If it appears that the patient may have
strep throat, the doctor will do laboratory tests.
3547

Strep throat

Strep throat

have a fever of 101–1048F (38.3–408C). The tongue
becomes bright red, with a flecked, strawberry-like
appearance. When a rash develops, this form of strep
throat is called scarlet fever. The rash is a reaction to
toxins released by the streptococcus bacteria. Scarlet
fever is no more dangerous than strep throat, and is
treated the same way. The rash disappears in about
five days. One to three weeks later, patches of skin may
peel off, as might occur with a sunburn, especially on
the fingers and toes.

Strep throat

In the event that rheumatic fever is suspected, the
doctor does a blood test. This test, called an antistreptolysin-O test, will tell the doctor whether the person
has recently been infected with strep bacteria. This
helps the doctor distinguish between rheumatic fever
and rheumatoid arthritis.

Treatment
Strep throat is treated with antibiotics. Penicillin
is the preferred medication. Oral penicillin must be
taken for 10-days. Patients need to take the entire
amount of antibiotic prescribed and not discontinue
taking the medication when they feel better. Stopping
the antibiotic early can lead to a return of the strep
infection. Occasionally, a single injection of long-acting penicillin (Bicillin) is given instead of 10 days of
oral treatment.

A thermographic image showing a streptococcal sore throat,
or strep throat. (Photograph by Howard Sochurek, The Stock
Market. Reproduced by permission.)

There are two types of tests to determine if a
person has strep throat. A rapid strep test can only
determine the presence of streptococcal bacteria, but
will not tell if the sore throat is caused by another kind
of bacteria. The results are available in about 20 minutes. The advantage of this test is the speed with which
a diagnosis can be made.
The rapid strep test has a false negative rate of
about 20%. In other words, in about 20% of cases
where no strep is detected by the rapid strep test, the
patient actually does have strep throat. Because of
this, when a rapid strep test is negative, the doctor
often does a throat culture.
For a rapid strep test or a throat culture, a nurse
will use a sterile swab to reach down into the throat
and obtain a sample of material from the sore area.
The procedure takes only a few seconds, but may
cause gagging.
For a throat culture a sample of swabbed material
is cultured, or grown, in the laboratory on a medium
that allows technicians to determine what kind of
bacteria are present. Results take 24–48 hours. The
test is very accurate and will show the presence of
other kinds of bacteria besides Streptococci. It is
important not to take any leftover antibiotics before
visiting the doctor and having a throat culture. Even
small amounts of antibiotics can suppress the bacteria
and mask its presence in the throat culture.
3548

About 10% of the time, penicillin is not effective
against the strep bacteria. When this happens a doctor
may prescribe other antibiotics such as amoxicillin
(Amoxil, Pentamox, Sumox, Trimox), clindamycin
(Cleocin), or a cephalosporin (Keflex, Durocef,
Ceclor). Erythromycin (Eryzole, Pediazole, Ilosone),
another inexpensive antibiotic, is given to people who
are allergic to penicillin. Scarlet fever is treated with
the same antibiotics as strep throat.
Without treatment, the symptoms of strep throat
begin subsiding in four or five days. However, because
of the possibility of getting rheumatic fever, it is
important to treat strep throat promptly with antibiotics. If rheumatic fever does occur, it is also treated
with antibiotics. Anti-inflammatory drugs, such as
steroids, are used to treat joint swelling. Diuretics are
used to reduce water retention. Once the rheumatic
fever becomes inactive, children may continue on low
doses of antibiotics to prevent a reoccurrence.
Necrotizing fasciitis is treated with intravenous
antibiotics.
Home care for strep throat
There are home care steps that people can take to
ease the discomfort of their strep symptoms.


Take acetaminophen or ibuprofen for pain. Aspirin
should not be given to children because of its association with an increase in Reye’s Syndrome, a serious disease.



Gargle with warm double strength tea or warm salt
water, made by adding one teaspoon of salt to eight
ounces of water, to relieve sore throat pain.



Drink plenty of fluids, but avoid acidic juices like
orange juice because they irritate the throat.
GALE ENCYCLOPEDIA OF MEDICINE

Eat soft, nutritious foods like noodle soup. Avoid
spicy foods.



Avoid smoke and smoking.



Rest until the fever is gone, then resume strenuous
activities gradually.



Use a room humidifier, as it may make sore throat
sufferers more comfortable.



Be aware that antiseptic lozenges and sprays may
aggravate the sore throat rather than improve it.

Alternative treatment
Alternative treatment focuses on easing the symptoms of strep throat through herbs and botanical
medicines. Some practitioners suggest using these
treatments in addition to antibiotics, since they primarily address the comfort of the patient and not the
underlying infection. Many practitioners recommend
Lactobacillus acidophilus to offset the suppressive
effects of antibiotics on the beneficial bacteria of the
intestines.
Some suggested treatments include:






Inhaling fragrances of the essential oils of lavender
(Lavandula officinalis), thyme (Thymus vulgaris),
eucalyptus (Eucalyptus globulus), sage (Salvia officinalis), and sandalwood (Aromatherapy).
Gargling with a mixture of water, salt, and tumeric
(Curcuma longa) powder or astringents, such as
alum, sumac, sage, and bayberry (Ayurvedic
medicine).
Taking osha root (Ligusticum porteri) internally for
infection or drinking tea made of sage, echinacea
(Echinacea spp.) and cleavers (Gallium aparine)
Osha root has an unpleasant taste many children
will not accept (Botanical medicine).

Prognosis
Patients with strep throat begin feeling better
about 24 hours after starting antibiotics. Symptoms
rarely last longer than five days.
People remain contagious until after they have
been taking antibiotics for 24 hours. Children should
not return to school or childcare until they are no
longer contagious. Food handlers should not work
for the first 24 hours after antibiotic treatment,
because strep infections are occasionally passed
through contaminated food. People who are not
treated with antibiotics can continue to spread strep
bacteria for several months.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Lactobacillus acidophilus—A bacteria found in
yogurt that changes the balance of the bacteria in
the intestine in a beneficial way.

About 10% of strep throat cases do not respond
to penicillin. People who have even a mild sore throat
after a 10 day treatment with antibiotic should return
to their doctor. An explanation for this may be that the
person is just a carrier of strep, and that something else
is causing the sore throat.
Taking antibiotics within the first week of a strep
infection will prevent rheumatic fever and other complications. If rheumatic fever does occur, the outcomes
vary considerably. Some cases may be cured. In others
there may be permanent damage to the heart and heart
valves. In rare cases, rheumatic fever can be fatal.
Necrotizing fasciitis has a death rate of 30–50%.
Patients who survive often suffer a great deal of tissue
and muscle loss. Fortunately, this complication of a
streptococcus infection is very rare.

Prevention
There is no way to prevent getting a strep throat.
However, the risk of getting one or passing one on to
another person can be minimized by:


sashing hands well and frequently, especially after
nose blowing or sneezing and before food handling



disposing of used tissues properly



avoiding close contact with someone who has a strep
throat



not sharing food and eating utensils with anyone



not smoking

Resources
OTHER

‘‘Group A Streptococcal Infections.’’ National Institute of
Allergy and Infectious Diseases Page. February 22,
1998. <http://www.niaid.nih.govfactsheets/
strep.htm.>.

Tish Davidson, A.M.

Streptobacillary rat-bite fever see Rat-bite
fever
3549

Strep throat



Streptococcal antibody tests

Streptococcal antibody tests
Definition
Streptococcal infections are caused by a microorganism called Streptococcus. Three streptococcal
antibody tests are available: the antistreptolysin O
titer (ASO), the antideoxyribonuclease-B titer (antiDnase-B, or ADB), and the streptozyme test.

Purpose
The antistreptolysin O titer, or ASO, is ordered
primarily to determine whether a previous group A
Streptococcus infection has caused a poststreptococcal
disease, such as scarlet fever, rheumatic fever, or a
kidney disease called glomerulonephritis.
The anti-DNase-B (ADB) test is performed to
determine a previous infection of a specific type of
Streptococcus, group A beta-hemolytic Streptococcus.
Identification of infections of this type are particularly
important in suspected cases of acute rheumatic fever
(ARF) or acute glomerulonephritis.
Streptozyme is a screening test used to detect antibodies to several streptococcal antigens. An antigen is
a substance that can trigger an immune response,
resulting in production of an antibody as part of the
body’s defense against infection and disease.

Precautions
For the ASO test, increased levels of fats, called
beta lipoproteins, in the blood can neutralize streptolysin O and cause a false-positive ASO titer.
Antibiotics, which reduce the number of streptococci
and thereby suppress ASO production, may decrease
ASO levels. Steroids, which suppress the immune system, consequently may also suppress ASO production. Also Group A streptococcal infections of the
skin may not produce an ASO response. Antibiotics
also may decrease anti-DNase-B (ADB) levels.

Description
Streptococcal infections are caused by bacteria
known as Streptococcus. There are several diseasecausing strains of streptococci (groups A, B, C, D,
and G), which are identified by their behavior, chemistry, and appearance. Each group causes specific types
of infections and symptoms. These antibody tests are
useful for group A streptococci. Group A streptococci
are the most virulent species for humans and are the
cause of strep throat, tonsillitis, wound and skin
3550

infections, blood infections (septicemia), scarlet fever,
pneumonia, rheumatic fever, Sydenham’s chorea (formerly called St. Vitus’ dance), and glomerulonephritis.
Although symptoms may suggest a streptococcal
infection, the diagnosis must be confirmed by tests.
The best procedure, and one that is used for an acute
infection, is to take a sample from the infected area for
culture, a means of growing bacteria artificially in the
laboratory. However, cultures are useless about two to
three weeks after initial infection, so the ASO, antiDNase-B, and streptozyme tests are used to determine
if a streptococcal infection is present.
Antistreptolysin O titer (ASO)
The ASO titer is used to demonstrate the body’s
reaction to an infection caused by group A beta-hemolytic streptococci. Group A streptococci produce the
enzyme streptolysin O, which can destroy (lyse) red
blood cells. Because streptolysin O is antigenic (contains a protein foreign to the body), the body reacts by
producing antistreptolysin O (ASO), which is a neutralizing antibody. ASO appears in the blood serum one
week to one month after the onset of a strep infection. A
high titer (high levels of ASO) is not specific for any
type of poststreptococcal disease, but it does indicate if
a streptococcal infection is or has been present.
Serial (several given in a row) ASO testing is often
performed to determine the difference between an
acute or convalescent blood sample. The diagnosis of
a previous strep infection is confirmed when serial
titers of ASO rise over a period of weeks, then fall
slowly. ASO titers peak during the third week after the
onset of acute symptoms of a streptococcal disease; at
six months after onset, approximately 30% of patients
exhibit abnormal titers.
Antideoxyribonuclease-B titer (anti-DNase B,
or ADB)
Anti-DNase-B, or ADB, also detects antigens
produced by group A strep, and is elevated in most
patients with rheumatic fever and poststreptococcal
glomerulonephritis. This test is often done concurrently with the ASO titer, and subsequent testing is
usually performed to detect differences in the acute
and convalescent blood samples. When ASO and
ADB are performed concurrently, 95% of previous
strep infections are detected. If both are repeatedly
negative, the likelihood is that the patient’s symptoms
are not caused by a poststreptococcal disease.
When evaluating patients with acute rheumatic
fever, the American Heart Association recommends
the ASO titer rather than ADB. Even though the ADB
GALE ENCYCLOPEDIA OF MEDICINE

Streptozyme
The streptozyme test is often used as a screening test
for antibodies to the streptococcal antigens NADase,
DNase, streptokinase, streptolysin O, and hyaluronidase. This test is most useful in evaluating suspected
poststreptococcal disease following Streptococcus
pyogenes infection, such as rheumatic fever.
Streptozyme has certain advantages over ASO and
ADB. It can detect several antibodies in a single assay,
it is technically quick and easy, and it is unaffected by
factors that can produce false-positives in the ASO test.
The disadvantages are that, while it detects different
antibodies, it does not determine which one has been
detected, and it is not as sensitive in children as in
adults. In fact, borderline antibody elevations, which
could be significant in children, may not be detected at
all. As with the ASO and ADB, a serially rising titer is
more significant than a single determination.

Preparation
These tests are performed on blood specimens
drawn from the patient’s vein. The patient does not
need to fast before these tests.

Risks
The risks associated with these tests are minimal,
but may include slight bleeding from the blooddrawing site, fainting or feeling lightheaded after the
blood is drawn, or blood accumulating under the
puncture site (hematoma).

Normal results

KEY TERMS
Antibody—A protein manufactured by a type of
white blood cells called lymphocytes, in response
to the presence of an antigen, or foreign protein, in
the body. Because bacteria, viruses, and other
organisms commonly contain many antigens, antibodies are formed against these foreign proteins to
neutralize or destroy the invaders.
Antigen—A substance that can trigger a defensive
response in the body, resulting in production of an
antibody as part of the body’s defense against infection and disease. Many antigens are foreign proteins not found naturally in the body, and include
bacteria, viruses, toxins, and tissues from another
person used in organ transplantation.
Glomerulonephritis—An inflammation of the glomeruli, the filtering units of the kidney. Damage to
these structures hampers removal of waste products, salt, and water from the bloodstream,
which may cause serious complications. This disorder can be mild and cause no symptoms, or so
severe enough to cause kidney failure.
Rheumatic fever—A disease that causes inflammation in various body tissues. Rare in most developed countries, but reported to be on the increase
again in parts of the United States. Joint inflammation occurs, but more serious is the frequency with
which the disease permanently damages the heart.
The nervous system may also be affected, causing
Sydenham’s chorea.
Sydenham’s chorea—A childhood disorder of the
central nervous system. Once called St. Vitus’
dance, the condition is characterized by involuntary, jerky movements that usually follow an attack
of rheumatic fever. Rare in the United States today,
but a common disorder in developing countries.
Usually resolves in two to three months with no
long-term adverse effects.

Antistreptolysin O titer:


adult: 160 Todd units/ml



child: six months to two years: 50 Todd units/ml; two
to four years: 160 Todd units/ml; five to 12 years:
170–330 Todd units/ml



newborn: similar to the mother’s value
Antideoxyribonuclease-B titer:



adult: 85 units



child (preschool): 60 units



child (school age): 170 units

GALE ENCYCLOPEDIA OF MEDICINE

Streptozyme: less than 100 streptozyme units.

Abnormal results
Antistreptolysin O titer: Increased levels are seen
after the second week of an untreated infection in
acute streptococcal infection, and are also increased
with acute rheumatic fever, acute glomerulonephritis
(66% of patients will not have high ASO titers), and
scarlet fever.
3551

Streptococcal antibody tests

is more sensitive than ASO, its results are too variable.
It also should be noted that, while ASO is the recommended test, when ASO and ADB are done together,
the combination is better than either ASO or ADB
alone.

Streptococcal infections

Antideoxyribonuclease-B titer: Increased titers
are seen in cases of acute rheumatic fever and poststreptococcal glomerulonephritis.
Streptozyme: As this is a screening test for antibodies to streptococcal antigens, increased levels
require more definitive tests to confirm diagnosis.
Resources
BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores

Streptococcal gangrene see Gangrene

Streptococcal infections
Definition
Streptococcal (strep) infections are communicable
diseases that develop when bacteria normally found
on the skin or in the intestines, mouth, nose, reproductive tract, or urinary tract invade other parts of the
body and contaminate blood or tissue.
Some strep infections don’t produce symptoms.
Some are fatal.

Description
Most people have some form of strep bacteria in
their body at some time. A person who hosts bacteria
without showing signs of infection is considered a
carrier.
Types of infection
Primary strep infections invade healthy tissue,
and most often affect the throat. Secondary strep
infections invade tissue already weakened by injury
or illness. They frequently affect the bones, ears,
eyes, joints, or intestines.
Both primary and secondary strep infections can
travel from affected tissues to lymph glands, enter the
bloodstream, and spread throughout the body.
Numerous strains of strep bacteria have been
identified. Types A, B, C, D, and G are most likely
to make people sick.
3552

Group A
Group A strep (GAS) is the form of strep bacteria
most apt to be associated with serious illness.
Between 10,000 and 15,000 GAS infections occur
in the United States every year. Most are mild inflammations of the throat or skin, where the bacteria are
normally found; however, GAS infections can be
deadly.
Two of the most severe invasive GAS infections
are necrotizing fasciitis or flesh-eating bacteria
(destruction of muscle tissue and fat) and toxic shock
syndrome (a rapidly progressive disorder that causes
shock and damages internal organs).
GROUP B. Group B strep (GBS) most often affects
pregnant women, infants, the elderly, and chronically
ill adults.

Since first emerging in the 1970s, GBS has been
the primary cause of life-threatening illness and death
in newborns. GBS exists in the reproductive tract of
20-25% of all pregnant women. Although no more
than 2% of these women develop invasive infection,
40-73% transmit bacteria to their babies during
delivery.
About 12,000 of the 3.5 million babies born in the
United States each year develop GBS disease in
infancy. About 75% of them develop early-onset
infection. Sometimes evident within a few hours of
birth and always apparent within the first week of
life, this condition causes inflammation of the membranes covering the brain and spinal cord (meningitis),
pneumonia, blood infection (sepsis) and other
problems.
Late-onset GBS develops between the ages of
seven days and three months. It often causes meningitis. About half of all cases of this rare condition can be
traced to mothers who are GBS carriers. The cause of
the others is unknown.
GBS has also been linked to a history of breast
cancer.
GROUP C. Group C strep (GCS) is a common
source of infection in animals. It rarely causes human
illness.
GROUP D. Group D strep (GDS) is a common
cause of wound infections in hospital patients. GDS
is also associated with:


abnormal growth of tissue in the gastrointestinal
tract



urinary tract infection (UTI)



womb infections in women who have just given birth
GALE ENCYCLOPEDIA OF MEDICINE

Streptococcal infections

GROUP G. Normally present on the skin, in the
mouth and throat, and in the intestines and genital
tract, Group G strep (GGS) is most likely to lead to
infection in alcoholics and in people who have cancer,
diabetes mellitus, rheumatoid arthritis, and other
conditions that suppress immune-system activity.

GGS can cause a variety of infections, including:


bacteria in the bloodstream (bacteremia)



inflammation of the connective tissue structure
surrounding a joint (bursitis)



endocarditis (a condition that affects the lining of the
heart chambers and the heart valves)



meningitis



inflammation of
(osteomyelitis)



inflammation of the lining of the abdomen
(peritonitis)

bone

and

bone

marrow

Causes and symptoms
Streptococcal infection occurs when bacteria contaminate cuts or open sores or otherwise penetrate the
body’s natural defenses.
GAS
GAS is transmitted by direct contact with saliva,
nasal discharge, or open wounds of someone who has
the infection. Chronic illness, kidney disease treated by
dialysis, and steroid use increase vulnerability to
infection.
About one of five people with GAS infection
develops a sore, inflamed throat, and pus on the tonsils. The majority of those infected by GAS either have
no symptoms or develop enlarged lymph nodes, fever,
headache, nausea, vomiting, weakness, and a rapid
heartbeat.
Flesh-eating bacteria is characterized by fever,
extreme pain, and swelling and redness at a site
where skin is broken.
Symptoms of toxic shock include abdominal pain,
confusion, dizziness, and widespread red skin rash.
GBS
A pregnant woman who has GBS infection can
develop infections of the bladder, blood, and urinary
tract, and deliver a baby who is infected or stillborn.
The risk of transmitting GBS infection during birth is
highest in a woman whose labor begins before the
37th week of pregnancy or lasts more than 18 hours or
who:
GALE ENCYCLOPEDIA OF MEDICINE

The scarlet fever rash on this person’s arm was caused by a
streptococcal infection. (Custom Medical Stock Photo.
Reproduced by permission.)



becomes a GBS carrier during the final stages of
pregnancy



has a GBS urinary-tract infection



has already given birth to a baby infected with GBS



develops a fever during labor

More than 13% of babies who develop GBS infection during birth or within the first few months of life
develop neurologic disorders. An equal number of
them die.
Among men, and in women who are not pregnant,
the most common consequences of GBS infection are
pneumonia and infections of blood, skin, and soft
tissue.
Miscellaneous symptoms
Other symptoms associated with strep infection
include:


anemia



elevated white blood cell counts



inflammation of the epiglottis (epiglottitis)



heart murmur



high blood pressure



infection of the heart muscle



kidney inflammation (nephritis)



swelling of the face and ankles

Diagnosis
Strep bacteria can be obtained by swabbing the
back of the throat or the rectum with a piece of sterile
cotton. Microscopic examination of the smear can
identify which type of bacteria has been collected.
3553

Stress

Treatment
Penicillin and other antibiotics are used to treat
strep infections.
It takes less than 24 hours for antibiotics to eliminate an infected person’s ability to transmit GAS.
Guidelines developed by the American Academy
of Obstetrics and Gynecology (AAOG), the American
Academy of Pediatrics (AAP), and the Centers for
Disease Control and Prevention (CDC) recommend
administering intravenous antibiotics to a woman at
high risk of passing GBS infection on to her child, and
offering the medication to any pregnant woman who
wants it.
Initiating antibiotic therapy at least four hours
before birth allows medication to become concentrated enough to protect the baby during passage
through the birth canal.
Babies infected with GBS during or shortly after
birth may die. Those who survive often require lengthy
hospital stays and develop vision or hearing loss and
other permanent disabilities.

Alternative treatment
Conventional medicine is very successful in treating strep infections. However, several alternative
therapies, including homeopathy and botanical
medicine, may help relieve symptoms or support the
person with a strep infection. For example, several
herbs, including garlic (Allium sativum), echinacea
(Echinacea spp.), and goldenseal (Hydrastis canadensis), are believed to strengthen the immune system,
thus helping the body fight a current infection, as
well as helping prevent future infections.

Prognosis
GAS is responsible for more than 2,000 deaths a
year. About 20% of people infected with flesh-eating
bacteria die. So do three of every five who develop
toxic shock syndrome.
Early-onset GBS kills 15% of the infants it affects.
Late-onset disease claims the lives of 10% of babies
who develop it.
GBS infections are fatal in about 20% of the men
and non-pregnant women who develop them.
About 10–15% of non-GAS strep infections
are fatal. Antibiotic therapy, begun when symptoms
first appear, may increase a patient’s chance of
survival.
3554

Prevention
Washing the hands frequently, especially before
eating and after using the bathroom, and keeping
wounds clean can help prevent strep infection.
Exposure to infected people should be avoided, and a
family physician should be notified by anyone who
develops an extremely sore throat or pain, redness,
swelling, or drainage at the site of a wound or break
in the skin.
Until vaccines to prevent strep infection become
available, 12 monthly doses of oral or injected antibiotics may prevent some types of recurrent infection.
Resources
OTHER

‘‘Infectious Diseases.’’ The Merck Page. June 17, 1998.
<http://www.merck.com>.

Maureen Haggerty

Streptococcal sore throat see Strep throat
Streptococcal toxic shock syndrome see
Toxic shock syndrome
Streptomycin see Aminoglycosides
Streptozyme test see Streptococcal antibody
tests

Stress
Definition
Stress is defined as an organism’s total response to
environmental demands or pressures. When stress was
first studied in the 1950s, the term was used to denote
both the causes and the experienced effects of these
pressures. More recently, however, the word stressor
has been used for the stimulus that provokes a stress
response. One recurrent disagreement among researchers concerns the definition of stress in humans. Is it
primarily an external response that can be measured
by changes in glandular secretions, skin reactions, and
other physical functions, or is it an internal interpretation of, or reaction to, a stressor; or is it both?

Description
Stress in humans results from interactions
between persons and their environment that are perceived as straining or exceeding their adaptive
GALE ENCYCLOPEDIA OF MEDICINE

Death of spouse
Divorce
Marital separation
Jail term or death of close family member
Personal injury or illness
Marriage
Loss of job due to termination
Marital reconciliation or retirement
Pregnancy
Change in financial state

capacities and threatening their well- being. The element of perception indicates that human stress
responses reflect differences in personality, as well as
differences in physical strength or general health.
Risk factors for stress-related illnesses are a mix of
personal, interpersonal, and social variables. These
factors include lack or loss of control over one’s physical environment, and lack or loss of social support
networks. People who are dependent on others
(e.g., children or the elderly) or who are socially disadvantaged (because of race, gender, educational
level, or similar factors) are at greater risk of developing stress-related illnesses. Other risk factors include
feelings of helplessness, hopelessness, extreme fear or
anger, and cynicism or distrust of others.

Causes and symptoms
Causes
The causes of stress can include any event or
occurrence that a person considers a threat to his or
her coping strategies or resources. Researchers generally agree that a certain degree of stress is a normal
part of a living organism’s response to the inevitable
changes in its physical or social environment, and that
positive, as well as negative, events can generate stress
as well as negative occurrences. Stress-related disease,
however, results from excessive and prolonged
demands on an organism’s coping resources. It is
now believed that 80–90% of all disease is stressrelated.
Recent research indicates that some vulnerability
to stress is genetic. Scientists at the University of
Wisconsin and King’s College London discovered
that people who inherited a short, or stress-sensitive,
version of the serotonin transporter gene were almost
three times as likely to experience depression following
GALE ENCYCLOPEDIA OF MEDICINE

One cause of stress that has affected large sectors of
the general population around the world since 2001 is
terrorism. The events of September 11, 2001, the sniper
shootings in Virginia and Maryland and the Bali nightclub bombing in 2002, the suicide bombings in the
Middle East in 2003, have all been shown to cause
short-term symptoms of stress in people who read
about them or watch television news reports as well as
those who witnessed the actual events. Stress related to
terrorist attacks also appears to affect people in countries far from the location of the attack as well as those
in the immediate vicinity. It is too soon to tell how stress
related to episodes of terrorism will affect human health
over long periods of time, but researchers are already
beginning to investigate this question. In 2004 the
Centers for Disease Control and Prevention (CDC)
released a report on the aftereffects of the World
Trade Center attacks on rescue and recovery workers
and volunteers. The researchers found that over half the
11,700 people who were interviewed met threshold criteria for a mental health evaluation. A longer-term
evaluation of these workers is underway.
A new condition that has been identified since 9/11
is childhood traumatic grief, or CTG. CTG refers to an
intense stress reaction that may develop in children
following the loss of a parent, sibling, or other loved
one during a traumatic event. As defined by the
National Child Traumatic Stress Network (NCTSN),
‘‘Children with childhood traumatic grief experience the
cause of [the loved one’s] death as horrifying or terrifying, whether the death was sudden and unexpected (for
example, due to homicide, suicide, motor vehicle accident,drug overdose, natural disaster, war, terrorism,
and so on) or due to natural causes (cancer, heart attack,
and so forth). Even if the manner of death does not
appear to others to be sudden, shocking, or frightening,
children who perceive the death in this way may develop
childhood traumatic grief. In this condition, even happy
thoughts and memories of the deceased person remind
children of the traumatic way in which the deceased
died.’’ More information on the identification and treatment of childhood traumatic grief can be obtained from
the NCTSN web site, <http://www.nctsnet.org/nccts/
nav.do?pid=hom_main>.
Symptoms
The symptoms of stress can be either physical or
psychological. Stress-related physical illnesses, such as
irritable bowel syndrome, heart attacks, arthritis, and
chronic
headaches,
result
from
long-term
3555

Stress

Top Ten Stressful Life Events

a stressful event as people with the long version of the
gene. Further research is likely to identify other genes
that affect susceptibility to stress.

Stress

overstimulation of a part of the nervous system that
regulates the heart rate, blood pressure, and digestive
system. Stress-related emotional illness results from
inadequate or inappropriate responses to major
changes in one’s life situation, such as marriage, completing one’s education, becoming a parent, losing a
job, or retirement. Psychiatrists sometimes use the
term adjustment disorder to describe this type of illness. In the workplace, stress-related illness often
takes the form of burnout—a loss of interest in or
ability to perform one’s job due to long-term high
stress levels. For example, palliative care nurses are
at high risk of burnout due to their inability to prevent
their patients from dying or even to relieve their physical suffering in some circumstances.

Diagnosis
When the doctor suspects that a patient’s illness is
connected to stress, he or she will take a careful history
that includes stressors in the patient’s life (family or
employment problems, other illnesses, etc.). Many
physicians will evaluate the patient’s personality as
well, in order to assess his or her coping resources
and emotional response patterns. There are a number
of personality inventories and psychological tests that
doctors can use to help diagnose the amount of stress
that the patient experiences and the coping strategies
that he or she uses to deal with them. A variation on
this theme is to identify what the patient perceives as
threatening as well as stressful. Stress-related illness
can be diagnosed by primary care doctors, as well as
by those who specialize in psychiatry. The doctor will
need to distinguish between adjustment disorders and
anxiety or mood disorders, and between psychiatric
disorders and physical illnesses (e.g., thyroid activity)
that have psychological side effects.

Treatment
Recent advances in the understanding of the many
complex connections between the human mind and
body have produced a variety of mainstream
approaches to stress-related illness. Present treatment
regimens may include one or more of the following:


Medications. These may include drugs to control
blood pressure or other physical symptoms of stress,
as well as drugs that affect the patient’s mood (tranquilizers or antidepressants).



Stress management programs. These may be either
individual or group treatments, and usually involve
analysis of the stressors in the patient’s life. They
often focus on job or workplace-related stress.

3556



Behavioral approaches. These strategies include
relaxation techniques, breathing exercises, and physical exercise programs including walking.



Massage. Therapeutic massage relieves stress by
relaxing the large groups of muscles in the back,
neck, arms, and legs.



Cognitive therapy. These approaches teach patients
to reframe or mentally reinterpret the stressors in
their lives in order to modify the body’s physical
reactions.



Meditation and associated spiritual or religious practices. Recent studies have found positive correlations
between these practices and stress hardiness.

Alternative treatment
Treatment of stress is one area in which the
boundaries between traditional and alternative
therapies have changed in recent years, in part
because some forms of physical exercise (yoga, tai
chi, aikido) that were once associated with the counterculture have become widely accepted as useful
parts of mainstream stress reduction programs.
Other alternative therapies for stress that are occasionally recommended by mainstream medicine
include aromatherapy, dance therapy, biofeedback,
nutrition-based treatments (including dietary guidelines and nutritional supplements), acupuncture,
homeopathy, and herbal medicine.

Prognosis
The prognosis for recovery from a stress-related
illness is related to a wide variety of factors in a person’s life, many of which are genetically determined
(race, sex, illnesses that run in families) or beyond the
individual’s control (economic trends, cultural stereotypes and prejudices). It is possible, however, for
humans to learn new responses to stress and, thus,
change their experiences of it. A person’s ability to
remain healthy in stressful situations is sometimes
referred to as stress hardiness. Stress-hardy people
have a cluster of personality traits that strengthen
their ability to cope. These traits include believing in
the importance of what they are doing; believing that
they have some power to influence their situation; and
viewing life’s changes as positive opportunities rather
than as threats.

Prevention
Complete prevention of stress is neither possible
nor desirable, because stress is an important stimulus
GALE ENCYCLOPEDIA OF MEDICINE

Adjustment disorder—A psychiatric disorder
marked by inappropriate or inadequate responses
to a change in life circumstances. Depression following retirement from work is an example of
adjustment disorder.
Biofeedback—A technique in which patients learn
to modify certain body functions, such as temperature or pulse rate, with the help of a monitoring
machine.
Burnout—An emotional condition, marked by
tiredness, loss of interest, or frustration, that interferes with job performance,. Burnout is usually
regarded as the result of prolonged stress.
Stress hardiness—A personality characteristic that
enables persons to stay healthy in stressful circumstances. It includes belief in one’s ability to influence the situation; being committed to or fully
engaged in one’s activities; and having a positive
view of change.
Stress management—A category of popularized
programs and techniques intended to help people
deal more effectively with stress.
Stressor—A stimulus, or event, that provokes a
stress response in an organism. Stressors can be
categorized as acute or chronic, and as external
or internal to the organism.

of human growth and creativity, as well as an inevitable part of life. In addition, specific strategies for stress
prevention vary widely from person to person,
depending on the nature and number of the stressors
in an individual’s life, and the amount of control he or
she has over these factors. In general, however, a
combination of attitudinal and behavioral changes
works well for most patients. The best form of prevention appears to be parental modeling of healthy attitudes and behaviors within the family.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychiatry in Medicine. ’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I, ‘‘Spirituality and Healing.’’ New York: Simon &
Schuster, 2002.
GALE ENCYCLOPEDIA OF MEDICINE

Blumenthal, J. A., M. Babyak, J. Wei, et al. ‘‘Usefulness of
Psychosocial Treatment of Mental Stress-Induced
Myocardial Ischemia in Men.’’ American Journal of
Cardiology 89 (January 15, 2002): 164-168.
Cardenas, J., K. Williams, J. P. Wilson, et al. ‘‘PSTD, Major
Depressive Symptoms, and Substance Abuse Following
September 11, 2001, in a Midwestern University
Population’’ International Journal of Emergency Mental
Health 5 (Winter 2003): 15–28.
Centers for Disease Control and Prevention. ‘‘Mental
Health Status of World Trade Center Rescue and
Recovery Workers and Volunteers—New York City,
July 2002–August 2004.’’ Morbidity and Mortality
Weekly Report 53 (September 10, 2004): 812–815.
Gallo, L. C., and K. A. Matthews. ‘‘Understanding the
Association Between Socioeconomic Status and
Physical Health: Do Negative Emotions Play a Role?’’
Psychological Bulletin 129 (January 2003): 10–51.
Goodman, R. F., A. V. Morgan, S. Juriga, and E. J. Brown.
‘‘Letting the Story Unfold: A Case Study of ClientCentered Therapy for Childhood Traumatic Grief.’’
Harvard Review of Psychiatry 12 (July-August 2004):
199–212.
Hawkley, L. C., and J. T. Cacioppo. ‘‘Loneliness and
Pathways to Disease.’’ Brain, Behavior, and Immunity
17, Supplement 1 (February 2003): S98–S105.
Latkin, C. A., and A. D. Curry. ‘‘Stressful Neighborhoods
and Depression: A Prospective Study of the Impact of
Neighborhood Disorder.’’ Journal of Health and Social
Behavior 44 (March 2003): 34–44.
Ottenstein, R. J. ‘‘Coping with Threats of Terrorism: A
Protocol for Group Intervention.’’ International
Journal of Emergency Mental Health 5 (Winter 2003):
39–42.
Ritchie, L. J. ‘‘Threat: A Concept Analysis for a New Era.’’
Nursing Forum 39 (July-September 2004): 13–22.
Surwit, R. S., M. A. van Tilburg, N. Zucker, et al. ‘‘Stress
Management Improves Long-Term Glycemic Control
in Type 2 Diabetes.’’ Diabetes Care 25 (January 2002):
30-34.
West, P., and H. Sweeting. ‘‘Fifteen, Female and Stressed:
Changing Patterns of Psychological Distress Over
Time.’’ Journal of Child Psychology and Psychiatry 44
(March 2003): 399–411.
White, K., L. Wilkes, K. Cooper, and M. Barbato. ‘‘The
Impact of Unrelieved Patient Suffering on Palliative
Care Nurses.’’ International Journal of Palliative
Nursing 10 (September 2004): 438–444.
ORGANIZATIONS

The American Institute of Stress. 124 Park Avenue,
Yonkers, NY 10703 (914) 963-1200. Fax: (914) 9656267. <http://www.stress.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
National Child Traumatic Stress Initiative. Center for
Mental Health Services, Substance Abuse and Mental
3557

Stress

PERIODICALS

KEY TERMS

Stress reduction

Health Services Administration, Department of Health
and Human Services, 5600 Fishers Lane, Parklawn
Building, Room 17C-26, Rockville, MD 20857. (301)
443-2940. <http://www.nctsnet.org/nccts/
nav.do?pid=hom_main>.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513. <http://
www.nimh.nih.gov>.
OTHER

National Center for Post-Traumatic Stress Disorder,
Department of Veterans Affairs. Fact Sheet: Survivors
of Human-Caused and Natural Disasters. <http://
www.ncptsd.org/facts/disasters/
fs_survivors_disaster.html>.
National Institute of Mental Health (NIMH) news release,
July 17, 2003. ‘‘Gene More Than Doubles Risk of
Depression Following Life Stresses.’’ <http://
www.nimh.nih.gov/events/prgenestress.cfm>.

Rebecca J. Frey, PhD

Stress reduction
Definition
Stress is the body’s normal response to anything
that disturbs its natural physical, emotional, or mental
balance. Stress reduction refers to various strategies
that counteract this response and produce a sense of
relaxation and tranquility.

Purpose
Although stress is a natural phenomenon of living, stress that is not controlled and that continues for
a long period of time can seriously compromise health.
For this reason, stress must be understood, managed
and appropriately reduced. Several very different strategies and therapies are available that help with relaxation and stress management.

Precautions
Stress reduction can only present a problem if an
individual attributes an actual, serious condition or
disease to being simply a stress-related response and
avoids consulting a physician.
People who have undergone a severe trauma
(criminal assault, combat, natural or transportation
disaster, etc.) may experience symptoms of posttraumatic stress disorder (PTSD) or acute stress
3558

disorder (ASD). These disorders are defined by their
temporal connection to a traumatic event in the
patient’s life, and are characterized by a cluster of
anxiety and dissociative symptoms. They interfere
with the patient’s normal level of functioning, and
require some form of supportive therapy. People who
experience a sense of detachment or unreality, emotional numbing, a general feeling of being dazed,
amnesia for part of the traumatic event, or similar
symptoms should consult a medical doctor in addition
to using other approaches to stress reduction.

Description
Everyone encounters stress every day. Although
most people think of it as something negative that
happens to them, in fact stress itself is really neither
good nor bad but is neutral or nonspecific. Stress may
be internal (from within ourselves) or external (such as
noise from the environment) and does not always
result from something unpleasant. A certain amount
of stress in our lives is actually essential to being
sufficiently stimulated to meet the challenges of everyday life, but when stress is constant and acute, it can
have dangerous consequences. Since stress is both
natural and unavoidable, it is necessary to understand
it and to learn how to deal with it, particularly how to
reduce it.
The specific and immediate cause of stress is called
the stressor. A stressor can be something dramatic or
terrible, such as a violent experience or the death of a
loved one, or it can be a positive and rewarding event,
like marriage or a promotion. The stressor can be
internal, such as feelings of guilt or anger felt in a
relationship, or it can be external, such as a natural
disaster or the ordinary rigors and frustrations of
commuting. It can also have a physical source, like
simple exercise or hard work, or it can be strictly
mental, like worry. Our bodies react the same way
physiologically no matter what the source and reasons
for stress might be.
From a physical standpoint, the body reacts to
stress in a standard and predictable manner. When
stress occurs, the brain immediately receives nerve
impulses. These impulses initiate an automatic
sequence carried out by the body’s sympathetic nervous system: it begins with stimulation of the brain’s
hypothalamus, which sends nerve impulses to both the
adrenal and the pituitary glands. Also called the ‘‘fight
or flight’’ response, this automatic physiological process is known to have evolved in humans and animals
to enable them to cope with sudden life-threatening
emergencies. When faced with a major stressor, the
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important to recognize that although stress itself is
not a disease, it can worsen any number of already
serious physical conditions. Many physicians feel that
chronic stress can so overtax an individual’s physical
resources and ways of coping that cancer, stroke, and
heart disease can occur. While long-term stress can
seriously affect one’s quality of life and lead to
major, sometimes fatal, diseases, prolonged stress
also results in the everyday miseries of headache and
allergy, digestive disorders and fatigue, irritable bladder and impotence, insomnia, anxiety, depression, and
simple aches and pains. Researchers exploring the
connection between stress and susceptibility to colds
exposed stressed individuals (who had experienced a
death in the family, become divorced, or had recently
moved) to cold viruses and then tested for antibodies a
month later. Results indicated that severely stressed
individuals were four times more likely to become
infected.

While these automatic physiological responses
served early man well and were essential to survival
of the species, today’s men and women rarely must
literally fight for their lives or dodge and elude a predator. Yet their bodies’ automatic response to stress
has remained unchanged in a radically changed, modern world. Whether caveman or corporate executive,
when the fight-or-flight response kicks in, a threestage process begins. Stage one is the alarm stage in
which the body releases hormones and prepares for
extreme physical action. Resistance is stage two in
which the body attempts to resist yet adapt to the
stress and to repair any damage done. The final
stage, exhaustion, occurs if the stress remains constant. It is especially dangerous since stage one’s physical response may begin all over again. The
persistence of stress and stage three’s exhaustion is
the point at which disease can occur. The body may
then experience severe debilitating conditions like
migraine, heart irregularities, and mental illness. The
body’s functions may even shut down altogether.

It follows that if stress can cause or contribute to
illness, then reducing stress should have the opposite
effect and perhaps even encourage healing. Probably
the most important step toward reducing the stress in
everyone’s life is to understand the nature of stress and
to learn how to condition ourselves to be able to gain
some control over it. Being able to recognize that we
are stressed is probably the first step toward understanding. Of the many signs and symptoms that alert
us, some are obvious and require only common sense
to recognize. Short-term noticeable effects of stress
include sweaty palms and other types of perspiration,
dilated pupils, and difficulty in swallowing (‘‘a lump in
the throat’’). Tightness in the chest is another stress
signal as are stomach problems and some skin conditions. Stress that is the result of prolonged anxiety (a
sense of apprehension) often results in feelings of panic
or actual trembling, fatigue, insomnia, and shortness
of breath, heart palpitations and dizziness, and sometimes simple irritability. Although none of these symptoms is pleasant, they are relatively minor compared to
the silent but much more serious internal effects that
can lead to immune-related disorders and even cancer
and heart disease.

Although different individuals may have different
levels of tolerance to stress, chronic stress will eventually wear down even the strongest of people.
Prolonged stress can cause biochemical imbalances
that weaken the immune system and invite serious
illness. Overall, stress that persists is known to interfere with digestion and, more seriously, alter brain
chemistry, create hormonal imbalances, increase
heart rate, raise blood pressure, and negatively affect
both metabolic and immune function. It is also

Fortunately, stress and the negative effects it creates can be reduced by a wide variety of therapeutic
approaches. When successfully applied, many of these
therapies or strategies can both reduce stress and
reverse its damage. Before selecting a particular therapy, it is important to be able distinguish bad or
unhealthy stress from the type that is not bad.
Researchers have found that the most important variable among types of stress is an individual’s sense of
control in a given situation. The least harmful stress

GALE ENCYCLOPEDIA OF MEDICINE

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Stress reduction

body’s biochemistry instantly hurtles into a ready
mode that marshals all the possible resources necessary to either escape or do battle. Thus, the adrenal
glands located on top of the kidneys provide an instant
surge of adrenaline, the body’s rocket fuel, quickening
the heart rate and blood flow and providing every cell
with extra oxygen. They also release cortisol or hydrocortisone, causing an increase in both amino acids (the
building blocks of proteins) and blood sugar. These
will be needed if tissue repair must take place. Finally,
the pituitary gland at the base of the brain releases a
variety of hormones, endorphins among them, that act
as natural painkillers and permit the body to do things
it ordinarily cannot do. Thus, at just about the same
time a stressor is recognized by the body, the heart and
breathing rate spikes, the pupils dilate to let in more
light, perspiration increases and digestion slows, and
the body is aroused, energized, and temporarily feels
no pain. This sequence of events allows individuals to
do whatever is required to save themselves, whether it
is to flee from a predator or engage in combat and fend
off an attack.

Stress reduction

scenario is one in which an individual has a sufficient
degree of control or some idea of predictability. Put
simply, predictable pain is less stressful because individuals know when to relax (gaining relief from pain as
well as protecting themselves from its damaging
effects). But when individuals have no warning of
pain, they are in a state of constant stress. An example
from daily life might be the difference between the
stress experienced by top executives who are in control
of their fate and their middle-level managers who are
not. The former can pick and choose when to enter or
engage a stressful situation or problem, but the latter
have no control nor any ability to predict when such a
situation will arise and are constantly on alert or in a
state of anxiety.
For those with little control over situations that
make them anxious, there are basically two ways to
deal with their stress. One is to remove or at least
reduce the stressor, and the other is to increase their
resistance to it. Although there are many strategies to
achieve each of these, all of them can be reduced to
some variation of a single simple concept—relaxation.
While there is no one single technique or therapy for
everyone to use to manage and reduce stress, there is
certainly some combination of lifestyle change, diet,
exercise, and relaxation that will allow all types of
individuals to better manage the stress in their lives.
Although relaxation is at the core of most stress reduction methods, it is not something that everyone can
fully achieve without assistance and guidance.
Interestingly, our modern life experiences often do
not provide us with the coping skills needed to deal
with stressful stimuli, and increasingly, people find
that simple relaxing is something that they must
learn how to do.
Fortunately, there are a number of relaxation
therapies that enable the willing individual to achieve
deep, beneficial relaxation. In fact, there are almost
too many from which to choose. A 1997 book on stress
remedies cowritten by the editors of Prevention magazine and published by Rodale Press is organized alphabetically and lists fifty-nine separate stress-reducing
techniques and subjects, from Acceptance to Yoga.
These and many other methods of reducing stress
can be grouped into the following general categories:
mind-body therapies, body work and movement
therapies, and herbal-based diets and natural regimens. Many of the specific techniques in these categories can be part of a self-help or self-care approach,
although some require the help of an experienced
practitioner.
Therapies that focus on the mind/body connection are based on the fact that thinking and emotions
3560

can have physical effects on the body. These techniques encourage the individual to take control and
learning how to cope with stressors rather than trying
to eliminate them. Such therapies range from individual counseling and meditation or involvement with a
support group to the mystery of guided imagery and
the technology of biofeedback. They all have the common goal of evoking the physiological relaxation
response, in which a person can achieve such beneficial
internal results as lowering blood pressure and
decreasing gastric acid secretion.
Body work and movement therapies include techniques ranging from dance therapy and the gentleness
of massage to reflexology and the rigors of rolfing. Body
work is based partly on the therapeutic power of human
touch and can also include manipulation, realignment,
and posture correction. Movement therapies are a particular form of physical exercise, although they attempt
to do much more than simply get a person into shape.
Most usually emphasize the mind/body connection and
strive to put people in better touch with both their
bodies and their feelings. Body work and movement
therapies can be as vigorous as deep tissue manipulation or as simple and minimal as the Alexander technique’s light posture corrections.
Herbal remedies for stress are usually part of a
larger system of natural, holistic medicine. Whether
Chinese traditional medicine, its counterpart from
India, or the homeopathy of the West, all these systems of natural medicine have a holistic focus and
emphasize the need for inner balance. All demonstrate
how the individual’s physical, emotional, mental, and
spiritual states are connected and use natural substances as part of the treatment for reducing stress.
Such therapies range from the occasional purging
(cleansing) of Ayurvedic medicine to the sleep-inducing
properties of chamomile tea. They also can include the
use of cayenne to relieve pain, fragrant essential oils
from flowers to evoke a pleasing response and relieve
tension, or aloe vera to soothe burned skin.
A list of some of the more common therapies and
techniques available for reducing stress includes:


Acupuncture. Insertion of needles at certain spots
under the skin for the purpose of attaining balance
by either releasing blocked energy or draining off
excess energy.



Alexander technique. Improving the alignment of
head, neck, and back claims to achieve efficient posture and movement.



Aromatherapy. Massage with essential oils from
flowers claims to affect mood and produce a sense
of well-being.
GALE ENCYCLOPEDIA OF MEDICINE

Art therapy. Creating something allows free expression and results in feelings of achievement and mood
change.



Autogenic training therapy. A form of deep meditation or self-hypnosis.
Autosuggestion therapy. A form of verbal therapy
involving repetition of a positive idea.







Massage. Use of touch and manipulation to soothe.
Can also employ vigorous deep tissue manipulation.



Meditation. Deep, relaxed, receptive, and focused
concentration on a single object, sound, or word.



Music therapy. Playing or listening to music to create
an emotional reaction.



Naturopathy. A complete health care system that
uses a variety of natural healing therapies.



Psychotherapy. A talking-based therapy with a mental health professional to get at the root of a conflict,
modify behavior and disruptive negative thought
patterns.



Reflexology. Manipulation of zones of the feet that
relate to the major organs, glands, and areas of the
body.



Rolfing. Vigorous manipulation of the body’s connective tissue to restore ‘‘balance.’’



Shiatsu. Traditional Japanese finger pressure massage therapy.



Breathing for relaxation. Stylized breathing technique to control and lower body functions.

Sound therapy. Uses sound waves to slow the body’s
autonomic system.



Tai chi chuan. System of slow, continuous exercises
based on rhythm and equilibrium.

Counseling. Work with a therapist trained in talkingbased therapy.



Yoga. System of exercises that combines certain
positions with deep breathing and meditation.

Ayurvedic medicine. A complete system of daily living based on awareness of one’s particular
constitution.



Behavioral therapy. A variety of psychotherapies
that are based on changing ourselves by retraining.



Bach flower therapy. Herbal remedies that are prepared from flowers acting energetically to soothe the
mind and body.



Bioenergetics. A practice that encourages sudden
release of tensions by crying or kicking.



Biofeedback. Monitoring rates of body functions
and using data to influence and gain control over
autonomic functions.







Dance movement therapy. Freedom of expression
through movement.



Feldenkrais method. Slow, light movements alter
habits and reeducate neuromuscular system.



Flotation therapy. Floating in a soundproof tank
with no external stimulation.



Guided imagery. Creating a mental picture of what is
desired. Also called Creative imagery or
Visualization.



Herbal medicine. Uses substances derived from
plants as treatment instead of synthetic drugs.



Homeopathy. Uses minute doses of plant, animal,
and mineral substances to stimulate the body’s natural healing.



Hydrotherapy. Use of water internally and externally for healing purposes.



Hypnotherapy. Hypnosis in order to identify and
release patterns that keep an individual from a personal balance point.



Kinesiology. Uses muscle testing to correct imbalances in the body’s ‘‘energy system.’’ Also called
Touch for Health.

GALE ENCYCLOPEDIA OF MEDICINE

These and many other techniques, systems, and
therapies are available to the person searching for
some way to reduce and manage the stress of everyday life. Some methods are very simple and can be
easily learned, while others are high-tech and often
involve a practitioner. A search for common elements
among most of these stress-reducing systems reveals
several obvious strategies that nearly everyone can
employ on their own. However, it is important to
know and recognize the signals of stress. Further, it
is easier to resist the negative effects of stress by
eating properly and getting sufficient sleep and
exercise.
Nearly all stress-reducing systems are geared to
evoking some degree of beneficial mind/body relaxation, and most include some version of the following:


mental time out



deep breathing



meditation and singular focus



gentle, repetitive exercise

The best stress reduction system is the one that
works for the individual. Whether stress can be
relieved by laughter, mellow music, repetition of a
3561

Stress reduction



Stress reduction

single word, self-massage, vigorous activity, or
simply by doing everyday chores in a mindful state
of heightened awareness, it is important that stress
be recognized and managed every day. Studies have
shown that regular relaxation eventually makes
the body less responsive to its stress hormones and
acts as a sort of natural tranquilizer. People can
build their own immune defense against the stress
response.
Many companies have introduced workplace
stress management programs to improve their
employees’ health. These programs typically include
instruction on emotional refocusing or restructuring,
and have been shown to be beneficial in reducing the
participants’ blood pressure, heart rate, and other
signs of emotional upset. In addition, stress management programs designed for persons in specific highstress occupations (medicine, law enforcement, emergency response, etc.) have proved to be effective in
reducing burnout and helping members of these professions cope with the specific stresses of their respective jobs.
An additional general strategy for handling stress
in family life or the workplace is the cultivation of a
group of character traits that has been termed ‘‘psychological hardiness.’’ These traits include believing in
the importance of what one is doing; believing that one
has some power to influence the immediate situation;
and viewing life’s changes as positive opportunities
rather than as threats. These qualities are sometimes
referred to as the ‘‘3 Cs,’’ which stand for commitment, control and challenge. Approaches to stress
reduction that enhance these qualities are especially
beneficial to people.

Newer trends in stress reduction
One trend in stress reduction in the early 2000s is
the development of stress management programs or
stress reduction strategies tailored to specific categories of people, often defined by their occupation or
by a chronic health condition. For example, journalists who cover traumatic events are increasingly recognized as susceptible to developing posttraumatic stress
disorder. With regard to specific diseases, stress management programs have been pioneered as of 2004 for
patients with asthma or lupus erythematosus.
Another new trend in stress reduction is the development of programs designed for communities as well
as individuals. After the events of September 11, 2001,
many mental health professionals recognized that acts
of terrorism or mass violence affect large groups of
people, and that psychiatric interventions need to
3562

address stress as a group experience as well as an
individual one.

Risks
All relaxation-based therapies to reduce stress are
virtually free of serious risk.

Normal results
Learning how to manage stress has the short-term
benefits of giving people some sense of control in their
lives, providing them with positive coping strategies,
and making them more relaxed and healthier. The
long-term benefits can be a stronger immune system,
proper hormonal balance, and reduced susceptibility
to such serious, life-threatening diseases as heart disease and cancer.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, DC: American Psychiatric Association,
2000.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Anxiety Disorders.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psychiatry in Medicine. ’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I. ‘‘Spirituality and Healing.’’ New York: Simon &
Schuster, 2002.
PERIODICALS

Collins, P. A., and A. C. Gibbs. ‘‘Stress in Police Officers: A
Study of the Origins, Prevalence and Severity of StressRelated Symptoms Within a County Police Force.’’
Occupational Medicine (London) 53 (June 2003):
256–264.
Czech, T. ‘‘Journalists and Trauma: A Brief Overview.’’
International Journal of Emergency Mental Health 6
(Summer 2004): 159–162.
Greco, C. M., T. E. Rudy, and S. Manzi. ‘‘Effects of a StressReduction Program on Psychological Function, Pain,
and Physical Function of Systemic Lupus
Erythematosus Patients: A Randomized Controlled
Trial.’’ Arthritis and Rheumatism 51 (August 15, 2004):
625–634.
Lambert, V. A., C. E. Lambert, and H. Yamase.
‘‘Psychological Hardiness, Workplace Stress and
Related Stress Reduction Strategies.’’ Nursing and
Health Sciences 5 (June 2003): 181–184.
GALE ENCYCLOPEDIA OF MEDICINE

Adrenal gland—A pair of glands that rest on the top
of each kidney that produce steroids, such as sex
hormones and those concerned with metabolic
functions.
Amino acid—Organic acids that are the main components of proteins and are synthesized by living
cells.
Antibody—A type of protein produced in the blood
in response to a foreign substance that destroys the
intruding substance; it is responsible for immunity.

Hypothalamus—A part of the brain that controls some of the body’s automatic regulatory
functions.
Immune function—The state in which the body
recognizes foreign materials and is able to neutralize
them before they can do any harm.

Burnout—An emotional condition marked by tiredness, loss of interest, or frustration that interferes with
job performance. Burnout is usually regarded as the
result of prolonged stress.

Metabolic function—Those processes necessary for
the maintenance of a living organism.

Chronic—Long-term or frequently recurring.
Debilitating—Weakening, or reducing the strength of.
Dilate—To enlarge, open wide, or distend.
Endorphins—A group of proteins with powerful
pain-killing properties that originate naturally in the
brain.
Holistic—That which pertains to the entire person,
involving the body, mind, and spirit.
Hydrocortisone—A steroid hormone produced by
the adrenal glands that provides resistance to stress.

Macy, R. D., L. Behar, R. Paulson, et al. ‘‘CommunityBased, Acute Posttraumatic Stress Management: A
Description and Evaluation of a PsychosocialIntervention Continuum.’’ Harvard Review of
Psychiatry 12 (July-August 2004): 217–228.
McCraty, R., M. Atkinson, and D. Tomasino. ‘‘Impact of a
Workplace Stress Reduction Program on Blood
Pressure and Emotional Health in Hypertensive
Employees.’’ Journal of Alternative and Complementary
Medicine 9 (June 2003): 355–369.
Ritchie, E. C., M. Friedman, P. Watson, et al. ‘‘Mass
Violence and Early Mental Health Intervention: A
Proposed Application of Best-Practice Guidelines to
Chemical, Biological, and Radiological Attacks.’’
Military Medicine 169 (August 2004): 575–579.
Sotile, W. M., and M. O. Sotile. ‘‘Beyond Physician
Burnout: Keys to Effective Emotional Management.’’
Journal of Medical Practice Management 18 (May-June
2003): 314–318.
Wright, R. J. ‘‘Alternative Modalities for Asthma That
Reduce Stress and Modify Mood States: Evidence for
Underlying Psychobiologic Mechanisms.’’ Annals of
Allergy, Asthma and Immunology 93, no. 2, Supplement
1 (August 2004): S18–S23.
GALE ENCYCLOPEDIA OF MEDICINE

Impotence—The inability of the male to engage in
sexual intercourse because of insufficient erection.
Insomnia—Inability
conditions.

to

sleep

under

normal

Neuromuscular—Relating to nerve and muscle or
their interaction.
Physiological—Dealing with the functions and processes of the body.
Pituitary gland—A gland at the base of the brain
responsible for growth, maturation, and reproduction.
Sympathetic nervous system—That part of the autonomic nervous system that affects contraction of
muscles and blood vessels. Stimulation of this system
by a stressor triggers the production of hormones that
prepare the body for fight or flight
Therapeutic—Curative or healing.

ORGANIZATIONS

American Institute of Stress. 124 Park Avenue. Yonkers,
NY 10703. (914) 963-1200. <http://www.stress.org>.
American Psychiatric Association (APA). 1400 K Street,
NW, Washington, DC 20005. (888) 357-7924.
<http://www.psych.org>.
Center for Mindfulness. University of Massachusetts
Medical Center, 55 Lake Avenue North, Worcester,
MA 01655. (508) 856-2656. <http://
www.umassmed.edu/cfm>.
National Institute of Mental Health (NIMH) Office of
Communications. 6001 Executive Boulevard, Room
8184, MSC 9663, Bethesda, MD 20892-9663. (866)
615-NIMH or (301) 443-4513. <http://
www.nimh.nih.gov>.
OTHER

National Institute of Mental Health (NIMH). Anxiety
Disorders. NIH Publication No. 02-3879. Bethesda,
MD: NIMH, 2002.

Leonard C. Bruno, PhD
Rebecca J. Frey, PhD
3563

Stress reduction

KEY TERMS

Stress test

Stress test
Definition
Used to evaluate heart function, a stress test
requires that a patient exercises on a treadmill or
exercise bicycle while his or her heart rate, breathing,
blood pressure, electrocardiogram (ECG), and feeling
of well being are monitored.

Purpose
When the body is active, it requires more oxygen
than when it is at rest, and, therefore, the heart has to
pump more blood. Because of the increased stress on
the heart, exercise can reveal coronary problems that
are not apparent when the body is at rest. This is why
the stress test, though not perfect, remains the best
initial, noninvasive, practical coronary test.
The stress test helps doctors determine how well
the heart handles the increased demands imposed by
physical activity. It is particularly useful for evaluating
possible coronary artery disease, detecting inadequate
supply of oxygen-rich blood to the tissues of the heart
muscle (ischemia), and determining safe levels of exercise in people with existing heart disease.

Precautions
The exercise stress test carries a very slight risk (1
in 100,000) of causing a heart attack. For this reason,
the exercise stress test should be attended by a health
care professional with a defibrillator and other emergency equipment on standby.
The patient must be aware of the symptoms of a
heart attack and stop the test if he or she develops any
of the following symptoms:


an unsteady gait



confusion



skin is grayish or cold and clammy



dizziness or fainting



a drop in blood pressure



chest pain (angina)



irregular heart beat (cardiac arrhythmias)

Description
The technician affixes electrodes to specific areas
of the patient’s chest, using special adhesive patches
with a special gel that conducts electrical impulses.
Typically, electrodes are placed under each collarbone
3564

and each bottom rib, and six electrodes are placed
across the chest in a rough outline of the heart. Then
the technician attaches wires from the electrodes to an
ECG, which records the electrical activity picked up
by the electrodes.
The technician runs resting ECG tests while the
patient is lying down, then standing up, and then
breathing heavily for half a minute. These tests can
later be compared with the ECG tests performed while
the patient is exercising. The patient’s blood pressure
is taken and the blood pressure cuff is left in place, so
that blood pressure can be measured periodically
throughout the test.
The patient begins riding a stationary bicycle or
walking on a treadmill. Gradually the intensity of the
exercise is increased. For example, if the patient is
walking on a treadmill, the speed of the treadmill
increases and the treadmill is tilted upward to simulate
an incline. If the patient is on an exercise bicycle, the
resistance or ‘‘drag’’ is gradually increased. The
patient continues exercising at increasing intensity
until he or she reaches his or her target heart rate
(generally set at a minimum of 85% of the maximal
predicted heart rate based on the patient’s age) or
experiences severe fatigue, dizziness, or chest pain.
During this time, the patient’s heart rate, ECG pattern, and blood pressure are continually monitored.
In some cases, other tests, such as echocardiography or thallium scanning, are also used in conjunction with the exercise stress test. For instance, recent
studies suggest that women have a high rate of false
negatives (results showing no problem when one
exists) and false positives (results showing a problem
when one does not exist) with the stress test. They
may benefit from another test, such as exercise
echocardiography. People who are unable to exercise
may be injected with drugs that mimic the effects of
exercise on the heart and given a thallium scan, which
can detect the same abnormalities that an exercise
test can.

Preparation
Patients are usually instructed not to eat or smoke
for several hours before the test. They should also tell
the doctor about any medications they are taking.
They should wear comfortable sneakers and exercise
clothing.

Aftercare
After the test, the patient should rest until blood
pressure and heart rate return to normal. If all goes
GALE ENCYCLOPEDIA OF MEDICINE

Angina—Chest pain from a poor blood supply to
the heart muscle due to narrowing of the coronary
arteries.
Cardiac arrhythmia—An irregular heart rate or
rhythm.

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222.
<http://www.nhlbi.nih.gov>.

Coronary arteries—Two arteries that branch off
from the aorta and supply blood to the heart.
Defibrillator—A device that delivers an electric
shock to the heart muscle through the chest wall
in order to restore a normal heart rate.

Robert Scott Dinsmoor

False negative—Test results showing no problem
when one exists.
False positive—Test results showing a problem
when one does not exist.
Hypertrophy—The overgrowth of muscle.
Ischemia—Dimished supply of oxygen-rich blood
to an organ or area of the body.

Stridor
Definition
Stridor is a term used to describe noisy breathing
in general, and to refer specifically to a high-pitched
crowing sound associated with croup, respiratory
infection, and airway obstruction.

Description
well, and there are no signs of distress, the patient may
return to his or her normal daily activities.

Risks
There is a very slight risk of a heart attack from
the exercise, as well as cardiac arrhythmia (irregular
heart beats), angina, or cardiac arrest (about one in
100,000).

Normal results
A normal result of an exercise stress test shows
normal electrocardiogram tracings and heart rate,
blood pressure within the normal range, and no
angina, unusual dizziness, or shortness of breath.

Abnormal results
A number of abnormalities may show up on an
exercise stress test. An abnormal electrocardiogram
(ECG) may indicate deprivation of oxygen-rich
blood to the heart muscle (ST wave segment depression, for example), heart rhythm disturbances, or
structural abnormalities of the heart, such as overgrowth of muscle (hypertrophy). If the blood pressure
rises too high or the patient experiences distressing
symptoms during the test, the heart may be unable to
handle the increased workload. Stress test abnormalities usually require further evaluation and therapy.
GALE ENCYCLOPEDIA OF MEDICINE

Stridor occurs when erratic air currents attempt
to force their way through breathing passages narrowed by:


illness



infection



the presence of foreign objects



throat abnormalities

Stridor can usually be heard from a distance but is
sometimes audible only during deep breathing.
Someone who has stridor may crow and wheeze when:


inhaling



exhaling



inhaling and exhaling

Most common in young children, whose naturally
small airways are easily obstructed, stridor can be a
symptom of a life-threatening respiratory emergency.

Causes and symptoms
During childhood, stridor is usually caused by
infection of the cartilage flap (epiglottis) that covers
the opening of the windpipe to prevent choking during
swallowing. It can also be caused by a toy or other tiny
object the child has tried to swallow.
Laryngomalacia is a common cause of a rapid,
low-pitched form of stridor that may be heard when
3565

Stridor

Resources

KEY TERMS

Stroke

a baby inhales. This harmless condition does not
require medical attention. It usually disappears by
the time the child is 18 months old.
The most common causes of stridor in adults are:


abscess or swelling of the upper airway



paralysis or malfunction of the vocal cords



tumor.
Other common causes of stridor include:



enlargement of the thyroid gland (goiter)



swelling of the voice box (largyngeal edema)



narrowing of the windpipe (tracheal stenosis)

Life-threatening emergencies may require:


the insertion of a breathing tube through the mouth
and nose (tracheal intubation)



the insertion of a breathing tube directly into the
windpipe (tracheostomy)

Resources
BOOKS

Berkow, Robert, editor. The Merck Manual of Medical
Information: Home Edition. Whitehouse Station, NJ:
Merck & Co., Inc., 1997.

Maureen Haggerty

When stridor is caused by a condition that slowly
narrows the airway, crowing and wheezing may not
develop until the obstruction has become severe.

Diagnosis

Stroke

When stridor is present in a newborn, pediatricians and neonatologists look for evidence of:


heart defects inherent at birth (congenital)



neurological disorders



General toxicity.

If examinations do not reveal the reasons for the
baby’s noisy breathing, the air passages are assumed
to be the cause of the problem.
Listening to an older child or adult breathe
usually enables pediatricians, family physicians, and
pulmonary specialists to estimate where an airway
obstruction is located. The extent of the obstruction
can be calculated by assessing the patient’s:


complexion



chest movements



breathing rate



level of consciousness

X rays and direct examination of the voice box
(larynx) and breathing passages indicate the exact
location of the obstruction or inflammation. Flowvolume loops and pulse oximetry are diagnostic tools
used to measure how much air flows through the
breathing passages, and how much oxygen those passages contain.

Definition
A stroke is the sudden death of brain cells in a
localized area due to inadequate blood flow.

Description
A stroke occurs when blood flow is interrupted to
part of the brain. Without blood to supply oxygen and
nutrients and to remove waste products, brain cells
quickly begin to die. Depending on the region of the
brain affected, a stroke may cause paralysis, speech
impairment, loss of memory and reasoning ability,
coma, or death. A stroke also is sometimes called a
brain attack or a cerebrovascular accident (CVA).
Some important stroke statistics include:


more than one-half million people in the United
States experience a new or recurrent stroke each year



stroke is the third leading cause of death in the
United States and the leading cause of disability



stroke kills about 160,000 Americans each year, or
almost one out of three stroke victims



three million Americans are currently permanently
disabled from stroke



in the United States, stroke costs about $30 billion
per year in direct costs and loss of productivity



two-thirds of strokes occur in people over age 65 but
they can occur at any age



strokes affect men more often than women, although
women are more likely to die from a stroke

Pulmonary function tests may also be performed.

Treatment
The cause of this condition determines the way it
is treated.
3566

GALE ENCYCLOPEDIA OF MEDICINE

strokes affect blacks more often than whites, and are
more likely to be fatal among blacks

Stroke is a medical emergency requiring immediate treatment. Prompt treatment improves the chances
of survival and increases the degree of recovery that
may be expected. A person who may have suffered a
stroke should be seen in a hospital emergency room
without delay. Treatment to break up a blood clot, the
major cause of stroke, must begin within three hours
of the stroke to be effective. Improved medical treatment of all types of stroke has resulted in a dramatic
decline in death rates in recent decades. In 1950, nine
in ten died from stroke, compared to slightly less than
one in three in the twenty-first century. However,
about two-thirds of stroke survivors will have disabilities ranging from moderate to severe.

Causes and symptoms
Causes
There are four main types of stroke. Cerebral
thrombosis and cerebral embolism are caused by
blood clots that block an artery supplying the brain,
either in the brain itself or in the neck. These account
for 70–80% of all strokes. Subarachnoid hemorrhage
and intracerebral hemorrhage occur when a blood
vessel bursts around or in the brain.
Cerebral thrombosis occurs when a blood clot, or
thrombus, forms within the brain itself, blocking the
flow of blood through the affected vessel. Clots most
often form due to ‘‘hardening’’ (atherosclerosis) of
brain arteries. Cerebral thrombosis occurs most
often at night or early in the morning. Cerebral thrombosis is often preceded by a transient ischemic attack,
or TIA, sometimes called a ‘‘mini-stroke.’’ In a TIA,
blood flow is temporarily interrupted, causing shortlived stroke-like symptoms. Recognizing the occurrence of a TIA, and seeking immediate treatment, is
an important step in stroke prevention.
Cerebral embolism occurs when a blood clot from
elsewhere in the circulatory system breaks free. If it
becomes lodged in an artery supplying the brain, either
in the brain or in the neck, it can cause a stroke. The
most common cause of cerebral embolism is atrial fibrillation, a disorder of the heart beat. In atrial fibrillation,
the upper chambers (atria) of the heart beat weakly and
rapidly, instead of slowly and steadily. Blood within the
atria is not completely emptied. This stagnant blood
may form clots within the atria, which can then break
off and enter the circulation. Atrial fibrillation is a factor
in about 15% of all strokes. The risk of a stroke from
atrial fibrillation can be dramatically reduced with daily
use of anticoagulant medication.
GALE ENCYCLOPEDIA OF MEDICINE

Hemorrhage, or bleeding, occurs when a blood
vessel breaks, either from trauma or excess internal
pressure. The vessels most likely to break are those
with preexisting defects such as an aneurysm. An aneurysm is a ‘‘pouching out’’ of a blood vessel caused by a
weak arterial wall. Brain aneurysms are surprisingly
common. According to autopsy studies, about 6% of
all Americans have them. Aneurysms rarely cause
symptoms until they burst. Aneurysms are most likely
to burst when blood pressure is highest, and controlling
blood pressure is an important preventive strategy.
Intracerebral hemorrhage affects vessels within
the brain itself, while subarachnoid hemorrhage
affects arteries at the brain’s surface, just below the
protective arachnoid membrane. Intracerebral hemorrhages represent about 10% of all strokes, while subarachnoid hemorrhages account for about 7%.
In addition to depriving affected tissues of blood
supply, the accumulation of fluid within the inflexible
skull creates excess pressure on brain tissue, which can
quickly become fatal. Nonetheless, recovery may be
more complete for a person who survives hemorrhage
than for one who survives a clot, because the blood
deprivation effects usually are not as severe.
Death of brain cells triggers a chain reaction in
which toxic chemicals created by cell death affect other
nearby cells. This is one reason why prompt treatment
can have such a dramatic effect on final recovery.
Risk factors
Risk factors for stroke involve age, sex, heredity,
predisposing diseases or other medical conditions, use
of certain medications, and lifestyle choices:


Age and sex. The risk of stroke increases with age,
doubling for each decade after age 55. Men are more
likely to have a stroke than women.



Heredity. Blacks, Asians, and Hispanics have higher
rates of stroke than do whites, related partly to
higher blood pressure. People with a family history
of stroke are at greater risk.



Diseases. Stroke risk is increased for people with
diabetes, heart disease (especially atrial fibrillation),
high blood pressure, prior stroke, or TIA. Risk of
stroke increases tenfold for someone with one or
more TIAs.



Other medical conditions. Stroke risk increases with
obesity, high blood cholesterol level, or high red
blood cell count.



Hormone replacement therapy. In mid-2003, a large
clinical trial called the Women’s Health Initiative
was halted when researchers discovered several
3567

Stroke



Stroke

potentially dangerous effects of combined hormone
replacement therapy on postmenopausal women. In
addition to increasing the risk of some cancers and
dementia, combined estrogen and progesterone therapy increased risk of ischemic stroke by 31% among
study participants.


Lifestyle choices. Stroke risk increases with cigarette
smoking (especially if combined with the use of oral
contraceptives), low level of physical activity, alcohol
consumption above two drinks per day, or use of
cocaine or intravenous drugs.
Symptoms

Symptoms of an embolic stroke usually come on
quite suddenly and are at their most intense right from
the start, while symptoms of a thrombotic stroke come
on more gradually. Symptoms may include:


blurring or decreased vision in one or both eyes



severe headache, often described as ‘‘the worst headache of my life’’



weakness, numbness, or paralysis of the face, arm, or
leg, usually confined to one side of the body



dizziness, loss of balance or coordination, especially
when combined with other symptoms

Diagnosis
The diagnosis of stroke is begun with a careful
medical history, especially concerning the onset and
distribution of symptoms, presence of risk factors, and
the exclusion of other possible causes. A brief neurological exam is performed to identify the degree and
location of any deficits, such as weakness, incoordination, or visual losses.
Once stroke is suspected, a computed tomography
scan (CT scan) or magnetic resonance imaging (MRI)
scan is performed to distinguish a stroke caused by
blood clot from one caused by hemorrhage, a critical
distinction that guides therapy. Blood and urine tests
are done routinely to look for possible abnormalities.
Other investigations that may be performed to
guide treatment include an electrocardiogram, angiography, ultrasound, and electroencephalogram.

Treatment
Emergency treatment
Emergency treatment of stroke from a blood clot is
aimed at dissolving the clot. This ‘‘thrombolytic therapy’’ currently is performed most often with tissue plasminogen activator, or t-PA. t-PA must be administered
3568

within three hours of the stroke event. Therefore,
patients who awaken with stroke symptoms are ineligible for t-PA therapy, as the time of onset cannot be
accurately determined. t-PA therapy has been shown
to improve recovery and decrease long-term disability
in selected patients. t-PA therapy carries a 6.4% risk of
inducing a cerebral hemorrhage, and is not appropriate
for patients with bleeding disorders, very high blood
pressure, known aneurysms, any evidence of intracranial
hemorrhage, or incidence of stroke, head trauma, or
intracranial surgery within the past three months.
Patients with clot-related (thrombotic or embolic) stroke
who are ineligible for t-PA treatment may be treated
with heparin or other blood thinners, or with aspirin or
other anti-clotting agents in some cases.
Emergency treatment of hemorrhagic stroke is
aimed at controlling intracranial pressure. Intravenous
urea or mannitol plus hyperventilation is the most
common treatment. Corticosteroids also may be used.
Patients with reversible bleeding disorders, such as
those due to anticoagulant treatment, should have
these bleeding disorders reversed, if possible.
Surgery for hemorrhage due to aneurysm may be
performed if the aneurysm is close enough to the cranial surface to allow access. Ruptured vessels are
closed off to prevent rebleeding. For aneurysms that
are difficult to reach surgically, endovascular treatment may be used. In this procedure, a catheter is
guided from a larger artery up into the brain to reach
the aneurysm. Small coils of wire are discharged into
the aneurysm, which plug it up and block off blood
flow from the main artery.
Rehabilitation
Rehabilitation refers to a comprehensive program
designed to regain function as much as possible and
compensate for permanent losses. Approximately
10% of stroke survivors are without any significant
disability and able to function independently. Another
10% are so severely affected that they must remain
institutionalized for severe disability. The remaining
80% can return home with appropriate therapy, training, support, and care services.
Rehabilitation is coordinated by a team of medical professionals and may include the services of a
neurologist, a physician who specializes in rehabilitation medicine (physiatrist), a physical therapist, an
occupational therapist, a speech-language pathologist, a nutritionist, a mental health professional, and
a social worker. Rehabilitation services may be provided in an acute care hospital, rehabilitation hospital,
long-term care facility, outpatient clinic, or at home.
GALE ENCYCLOPEDIA OF MEDICINE

Stroke

A hemorrhagic stroke occurs
when a blood vessel ruptures
within the brain.

A thrombotic stroke occurs
when a blood clot blocks
a cerebral artery.

A hemorrhagic stroke (left) compared to a thrombotic stroke (right). (Illustration by Hans &Cassady, Inc.)

The rehabilitation program is based on the
patient’s individual deficits and strengths. Strokes on
the left side of the brain primarily affect the right half
of the body, and vice versa. In addition, in left brain
dominant people, who constitute a significant majority of the population, left brain strokes usually lead to
speech and language deficits, while right brain strokes
may affect spatial perception. Patients with right brain
strokes also may deny their illness, neglect the affected
side of their body, and behave impulsively.
Rehabilitation may be complicated by cognitive
losses, including diminished ability to understand and
follow directions. Poor results are more likely in
patients with significant or prolonged cognitive
changes, sensory losses, language deficits, or
incontinence.
GALE ENCYCLOPEDIA OF MEDICINE

PREVENTING COMPLICATIONS. Rehabilitation begins
with prevention of stroke recurrence and other medical complications. The risk of stroke recurrence may
be reduced with many of the same measures used to
prevent stroke, including quitting smoking and controlling blood pressure.

One of the most common medical complications following stroke is deep venous thrombosis,
in which a clot forms within a limb immobilized by
paralysis. Clots that break free often become
lodged in an artery feeding the lungs. This type
of pulmonary embolism is a common cause of
death in the weeks following a stroke. Resuming
activity within a day or two after the stroke is an
important preventive measure, along with use of
elastic stockings on the lower limbs. Drugs that
3569

Stroke

prevent clotting may be given, including intravenous heparin and oral warfarin.
Weakness and loss of coordination of the swallowing muscles may impair swallowing (dysphagia),
and allow food to enter the lower airway. This may
lead to aspiration pneumonia, another common cause
of death shortly after a stroke. Dysphagia may be
treated with retraining exercises and temporary use
of pureed foods.
Depression occurs in 30–60% of stroke patients.
Antidepressants and psychotherapy may be used in
combination.
Other medical complications include urinary tract
infections, pressure ulcers, falls, and seizures.
TYPES OF REHABILITATIVE THERAPY. Brain tissue
that dies in a stroke cannot regenerate. In some
cases, the functions of that tissue may be performed
by other brain regions after a training period. In other
cases, compensatory actions may be developed to
replace lost abilities.

Physical therapy is used to maintain and restore
range of motion and strength in affected limbs, and to
maximize mobility in walking, wheelchair use, and
transferring (from wheelchair to toilet or from standing to sitting, for instance). The physical therapist
advises on mobility aids such as wheelchairs, braces,
and canes. In the recovery period, a stroke patient may
develop muscle spasticity and contractures, or abnormal contractions. Contractures may be treated with a
combination of stretching and splinting.

patients and for caregivers. Joining a support group
can be one of the most important steps in the rehabilitation process.

Prognosis
Stroke is fatal for about 27% of white males, 52%
of black males, 23% of white females, and 40% of
black females. Stroke survivors may be left with significant deficits. Emergency treatment and comprehensive rehabilitation can significantly improve both
survival and recovery. A 2003 study found that treating people who have had a stroke with certain antidepressant medications, even if they were not
depressed, could increase their chances of living
longer. People who received the treatment were less
likely to die from cardiovascular events than those
who did not receive antidepressant drugs.

Prevention
Damage from stroke may be significantly reduced
through emergency treatment. Knowing the symptoms of stroke is as important as knowing those of a
heart attack. Patients with stroke symptoms should
seek emergency treatment without delay, which may
mean dialing 911 rather than their family physician.
The risk of stroke can be reduced through lifestyle
changes:


quitting smoking



controlling blood pressure

Occupational therapy improves self-care skills
such as feeding, bathing, and dressing, and helps
develop effective compensatory strategies and devices
for activities of daily living. A speech-language pathologist focuses on communication and swallowing skills.
When dysphagia is a problem, a nutritionist can advise
alternative meals that provide adequate nutrition.



getting regular exercise



keeping body weight down



avoiding excessive alcohol consumption



getting regular checkups and following the doctor’s
advice regarding diet and medicines, particularly
hormone replacement therapy.

Mental health professionals may be involved in
the treatment of depression or loss of thinking (cognitive) skills. A social worker may help coordinate services and ease the transition out of the hospital back
into the home. Both social workers and mental health
professionals may help counsel the patient and family
during the difficult rehabilitation period. Caring for a
person affected with stroke requires learning a new set
of skills and adapting to new demands and limitations.
Home caregivers may develop stress, anxiety, and
depression. Caring for the caregiver is an important
part of the overall stroke treatment program.

Treatment of atrial fibrillation may significantly
reduce the risk of stroke. Preventive anticoagulant
therapy may benefit those with untreated atrial fibrillation. Warfarin (Coumadin) has proven to be more
effective than aspirin for those with higher risk. A new
drug called ximelagatran (Exanta) with fewer side
effects has been introduced in Europe. The drug’s
manufacturer was applying for FDA approval to market the drug for use in preventing stroke and other
thromboembolic complications in early 2004.

Support groups can provide an important source
of information, advice, and comfort for stroke
3570

In 2003, physicians at the Framingham Heart
Study derived new risk scores to help physicians determine which patients with new onset of atrial fibrillation are at higher risk for stroke alone or for stroke or
GALE ENCYCLOPEDIA OF MEDICINE

Aneurysm—A pouchlike bulging of a blood vessel.
Aneurysms can rupture, leading to stroke.
Atrial fibrillation—A disorder of the heart beat
associated with a higher risk of stroke. In this disorder, the upper chambers (atria) of the heart do not
completely empty when the heart beats, which can
allow blood clots to form.
Cerebral embolism—A blockage of blood flow
through a vessel in the brain by a blood clot that
formed elsewhere in the body and traveled to the
brain.
Cerebral thrombosis—A blockage of blood flow
through a vessel in the brain by a blood clot that
formed in the brain itself.
Intracerebral hemorrhage—A cause of some
strokes in which vessels within the brain begin
bleeding.
Subarachnoid hemorrhage—A cause of some
strokes in which arteries on the surface of the
brain begin bleeding.
Tissue plasminogen activator (tPA)—A substance
that is sometimes given to patients within three
hours of a stroke to dissolve blood clots within the
brain.

death. Screening for aneurysms may be an effective
preventive measure in those with a family history of
aneurysms or autosomal polycystic kidney disease,
which tends to be associated with aneurysms.
Resources
PERIODICALS

‘‘HRT Increases Risk of Dementia and Stroke.’’
Contemporary OB/GYN July 2003: 16–21.
‘‘New Classification Scheme Helpful to Predict Risk of
Stroke or Death.’’ Heart Disease Weekly September 14,
2003: 3.
‘‘New Drug Application Submitted to FDA for Exanta.’’
Heart Disease Weekly January 25, 2004: 79.
‘‘New Stroke Prevention Drug.’’ Chemist & Druggist
September 13, 2003: 24.
‘‘Post-stroke Antidepressant Treatment Appears to
Reduce Death Rate.’’ Heart Disease Weekly October
26, 2003: 56.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
GALE ENCYCLOPEDIA OF MEDICINE

National Stroke Association. 9707 E. Easter Lane,
Englewood, Co. 80112. (800) 787-6537. <http://
www.stroke.org>.

Stuttering

KEY TERMS

Richard Robinson
Teresa G. Odle

Strongyloidiasis see Threadworm infection
Structural integration see Rolfing
Stupor see Coma

Stuttering
Definition
Stuttering is a speech problem characterized by
repetitions, pauses, or drawn out syllables, words, and
phrases. Stutterers are different than people experiencing normal fluency problems because a stutterer’s
disfluency is more severe and consistent than that of
people who do not stutter.

Description
Normal language development in a child can
include a period of disfluency. Children might repeat
syllables or words once or twice. Sometimes, children
experiencing normal disfluencies hesitate during
speech or use fillers, including ‘‘um,’’ with frequency.
These developmental problems usually happen
between one and five years of age. Often, parents are
concerned about the disfluency they hear in their children. In fact, about 25% of all children experience
speech disfluencies during development concern their
parents because of their severity.
A child with mild stuttering, however, will repeat
sounds more than twice. Parents and teachers often
notice the child’s facial muscles become tense and he
or she might struggle to speak. The child’s voice pitch
might rise with repetitions, and some children experience occasional periods when airflow or voice stops
for seconds at a time. Children with more severe stuttering stutter through more than 10% of their speech.
This child exhibits considerable tension and tries to
avoid stuttering by using different words. In these
children, complete blocks of speech are more common
than repetitions or prolongations, during which children lengthen syllables or words.
Stuttering usually begins in childhood when the
child is developing language skills, and it rarely
3571

Stuttering

develops in adulthood with only 1% of the population
affected by the disorder. Stuttering does not affect
intelligence. Teens often experience more noticeable
problems with stuttering as they enter the dating scene
and increase their social interactions. Stuttering can
severely affect one’s life. Often, adults who are concerned about stuttering choose their careers based on
the disability.
The degree of stuttering is often inconsistent.
Stutterers can be fluent in some situations. Many
find that they stop stuttering when singing or doing
other activities involving speech. Some have good and
bad days when it comes to stuttering. On good days, a
stutterer might be able to talk fluently using words
that usually cause him to repeat, pause or prolongate
sounds, syllables, parts of words, entire words, or
phrases.

Causes and symptoms
There is no known cause of stuttering. Some
believe that it has a physical cause and that it might
be related to a breakdown in the neurological system.
Stuttering starts early in life and often is inherited.
Brain scan research has revealed that there might be
abnormalities in the brains of stutterers, while they are
stuttering. Myths about why stuttering occurs
abound. Some cultures believe that stuttering is caused
by emotional problems, tickling an infant too much or
because a mother ate improperly during breastfeeding.
None have been proven to be true. It is believed that
some drugs might induce stuttering-like conditions.
These include antidepressants, antihistamines, tranquilizers and selective serotonin reuptake inhibitors.

Diagnosis
Speech and language therapists diagnose stuttering by asking stutterers to read out loud, pronounce
specific words, and talk. Some also order hearing tests.
The tests will determine whether or not a person needs
speech therapy.

KEY TERMS
Antipsychotics—A class of drugs used to treat psychotic or neurotic behavior.
Disfluency—An interruption in speech flow.
Neuroleptics—Antipsychotic drugs that affect psychomotor activity.

decrease the tension and struggle of stuttering, become
educated about stuttering, and learn to use effective
communications skills, such as making eye contact,
to further enhance speech. The therapy focuses on
helping stutterers to discover easier and different
ways of producing sounds and expressing thoughts.
The success of therapy depends largely on the stutterer’s willingness to work at getting better.
The duration of stuttering therapy needed varies
among stutterers. Sometimes, it helps stutterers if they
have therapy intermittently throughout their lives.
Parents, teachers and others can do things to help
ease stuttering. These include: talking slowly, but normally, clearly, and in a relaxed manner to a stutterer:
answering questions after a pause to encourage a
relaxed transaction; trying not to make stuttering
worse by getting annoyed by a person’s stuttering;
giving stutterers reassurance about their stuttering; and encourage the stutterer to talk about his
or her stuttering.
Electronic fluency aids help some stutterers when
used as an adjunct to therapy. Medications, such as
antipsychotics and neuroleptics, have been used to
treat stuttering with limited success.

Alternative treatment
Some use relaxation techniques to help their
stuttering.

Prognosis
Treatment
Researchers don’t understand what causes stuttering. However, progress has been made into what
contributes to the development of the disability and,
therefore, in some cases it can be prevented in childhood with the help of therapy early on. Therapy can
help people of all ages suffering from the speech disability. While not an overnight cure, therapy can offer
positive results and more fluent speech patterns. The
goals of therapy are to reduce stuttering frequency,
3572

More than three million Americans stutter and
four times more males are affected than females.
Winston Churchill, Marilyn Monroe, Carly Simon,
James Earl Jones and King George VI are among the
many people who stuttered but went on to live successful professional lives. Decades of research have yielded
no answers to the causes of stuttering; still much has
been learned about what contributes to stuttering’s
development and how to prevent it in children.
People who stutter can get better through therapy.
GALE ENCYCLOPEDIA OF MEDICINE

New and exciting developments are occurring in
researchers’ understanding of the genetics of stuttering. Researchers are finding the locations of genes that
predispose people to stuttering. While genetic factors
will not explain all stuttering, genetics will help to
uncover the disability’s causes. Speech therapy, especially that performed at a young age, can stop the
progression of stuttering.

KEY TERMS
Measles encephalitis—A serious complication of
measles occurring in about one out of every 1,000
cases, causing headache, drowsiness, and vomiting
seven to ten days after the rash appears. Seizures
and coma can follow, which may lead to retardation and death.

Resources
ORGANIZATIONS

National Stuttering Foundation of America. 1-(800) 9929392. <http://www.stutteringhelp.org>.
OTHER

The Stuttering Home Page. Minnesota State University,
Mankato. <http://www.mandato.msus.edu/deprt/
comdis/kuster/stutter.html>.
‘‘Stuttering.’’ The Nemours Foundation, KidsHealth.org.
<http://kidshealth.org>.
‘‘What is Stuttering?’’ Robert W. Quesal, PhD, Professor
and Program Director. Communications Sciences and
Disorders. Western Illinois University. <http://
www.wiu.edu>.

Lisette Hilton

Stye see Eyelid disorders

The condition begins with behavioral changes,
memory loss, irritability, and problems with school
work. As the neurological damage increases, the
child experiences seizures, involuntary movements,
and further neurological deterioration. Eventually,
the child starts suffering from progressive dementia.
The optic nerve begins to shrink and weaken (atrophy)
and subsequently the child becomes blind.

Diagnosis
Blood tests and spinal fluid reveal high levels of
antibodies to measles virus, and there is a characteristically abnormal electroencephalogram (EEG), or
brain wave test. Typically, there is a history of
measles infection two to ten years before symptoms
begin.

Treatment

Subacute sclerosing
panencephalitis
Definition
Subacute sclerosing panencephalitis is a rare, progressive brain disorder caused by an abnormal
immune response to the measles virus.

Description
This fatal condition is a complication of measles,
and affects children and young adults before the age of
20. It usually occurs in boys more often than in girls,
but is extremely rare, appearing in only one out of a
million cases of measles.

Causes and symptoms
Experts believe this condition is a form of measles
encephalitis (swelling of the brain), caused by an
improper response by the immune system to the
measles virus.
GALE ENCYCLOPEDIA OF MEDICINE

There is no standard treatment, and a number of
antiviral drugs have been tested with little success.
Treatment of symptoms, including the use of anticonvulsant drugs, can be helpful.

Prognosis
While there may be periodic remissions during the
course of this disease, it is usually fatal (often from
pneumonia) within one to three years after onset.
Resources
ORGANIZATIONS

National Institute of Allergy and Infectious Disease.
Building 31, Room 7A-50, 31 Center Drive MSC 2520,
Bethesda, MD 20892-2520. (301) 496-5717. <http://
www.niaid.nih.gov/default.htm>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Carol A. Turkington
3573

Subacute sclerosing panencephalitis

Prevention

Subarachnoid hemorrhage

Subacute spongiform encephalopathy see
Creutzfeldt-Jakob disease
Subacute thyroiditis see Thyroiditis

Subarachnoid hemorrhage
Definition
A subarachnoid hemorrhage is an abnormal and
very dangerous condition in which blood collects
beneath the arachnoid mater, a membrane that covers
the brain. This area, called the subarachnoid space,
normally contains cerebrospinal fluid. The accumulation of blood in the subarachnoid space can lead to
stroke, seizures, and other complications. Additionally,
subarachnoid hemorrhages may cause permanent brain
damage and a number of harmful biochemical events in
the brain. A subarachnoid hemorrhage and the related
problems are frequently fatal.

Description
Subarachnoid hemorrhages are classified into two
general categories: traumatic and spontaneous.
Traumatic refers to brain injury that might be sustained in an accident or a fall. Spontaneous subarachnoid hemorrhages occur with little or no warning and
are frequently caused by ruptured aneurysms or blood
vessel abnormalities in the brain.
Traumatic brain injury is a critical problem in the
United States. According to annual figures compiled
by the Brain Injury Association, approximately
373,000 people are hospitalized, more than 56,000
people die, and 99,000 survive with permanent disabilities due to traumatic brain injuries. The leading
causes of injury are bicycle, motorcycle, and automobile accidents, with a significant minority due to accidental falls, and sports and recreation mishaps.
Exact statistics are not available on traumatic
subarachnoid hemorrhages, but several large clinical
studies have found an incidence of 23–39% in relation
to severe head injury. Furthermore, subarachnoid
hemorrhages have been described in the medical literature as the most common brain injury found during
autopsy investigations of head trauma.
Spontaneous subarachnoid hemorrhages are
often due to an aneurysm (a bulge or sac-like projection from a blood vessel) which bursts. Arteriovenous
malformations (AVMs), which are abnormal interfaces between arteries and veins, may also rupture
3574

and release blood into the subarachnoid space.
Both aneurysms and AVMs are associated with
weak spots in the walls of blood vessels and account
for approximately 60% of all spontaneous subarachnoid hemorrhages. The rest may be attributed to
other causes, such as cancer or infection, or are of
unknown origin.
In industrialized countries, it is estimated that
there are 6.5–26.4 cases of spontaneous subarachnoid
hemorrhage per 100,000 people annually. Certain factors raise the risk of suffering a hemorrhage.
Aneurysms are acquired over a person’s lifetime and
are rarely a factor in subarachnoid hemorrhage before
age 20. Conversely, AVMs are present at birth. In
some cases, there may be a genetic predisposition for
aneurysms or AVMs. Other factors that have been
implicated, but not definitively linked to spontaneous
subarachnoid hemorrhages, include atherosclerosis,
cigarette use, extreme alcohol consumption, and the
use of illegal drugs, such as cocaine. The exact role of
high blood pressure is somewhat unclear, but since it
does seem linked to the formation of aneurysms, it
may be considered an indirect risk factor.
The immediate danger due to subarachnoid
hemorrhage, whether traumatic or spontaneous, is
ischemia. Ischemia refers to tissue damage caused by
restricted or blocked blood flow. The areas of the
brain that do not receive adequate blood and oxygen
can suffer irreparable injury, leading to permanent
brain damage or death. An individual who survives
the initial hemorrhage is susceptible to a number of
complications in the following hours, days, and weeks.
The most common complications are intracranial
hypertension,
vasospasm,
and
hydrocephalus.
Intracranial hypertension, or high pressure within
the brain, can lead to further bleeding from damaged
blood vessels; a complication associated with a 70%
fatality rate. Vasospasm, or blood vessel constriction,
is a principal cause of secondary ischemia. The blood
vessels in the brain constrict in reaction to chemicals
released by blood breaking down within the subarachnoid space. As the blood vessels become narrower,
blood flow in the brain becomes increasingly
restricted. Approximately one third of spontaneous
subarachnoid hemorrhages and 30-60% of traumatic
bleeds are followed by vasospasm. Hydrocephalus, an
accumulation of fluid in the chambers of the brain
(ventricles) due to restricted circulation of cerebrospinal fluid, follows approximately 15% of subarachnoid hemorrhages. Because cerebrospinal fluid
cannot drain properly, pressure accumulates on the
brain, possibly prompting further ischemic
complications.
GALE ENCYCLOPEDIA OF MEDICINE

Whether through trauma or disease, subarachnoid hemorrhages are caused by blood being released
by a damaged blood vessel and accumulating in the
subarachnoid space. Symptoms associated with traumatic subarachnoid hemorrhage may or may not
resemble those associated with spontaneous hemorrhage, as trauma can involve multiple injuries with
overlapping symptoms.
Typically, a spontaneous subarachnoid hemorrhage is indicated by a sudden, severe headache.
Nausea, vomiting, and dizziness frequently accompany
the pain. Loss of consciousness occurs in about half
the cases of spontaneous hemorrhage. A coma, usually
brief, may occur. A stiff neck, fever, and aversion to
light may appear following the hemorrhage.
Neurologic symptoms may include partial paralysis,
loss of vision, seizures, and speech difficulties.
Spontaneous subarachnoid hemorrhages may be
preceded by warning signs prior to the initial bleed.
Sentinel, or warning, headaches may be present in the
days or weeks before an aneurysm or AVM ruptures.
These headaches can be accompanied by dizziness,
nausea, and vomiting, and possibly neurologic symptoms. Approximately 50% of AVMs are discovered
before they bleed significantly; however, most aneurysms are not diagnosed before they rupture.

Diagnosis
To make a diagnosis, a health-care provider takes
a detailed history of the symptoms and does a physical
examination. The symptoms may mimic other disorders and diagnosis can be complicated, especially if the
individual is unconscious. The sudden, severe headache can fuel suspicion of a subarachnoid hemorrhage
or similar event, and a computed tomography scan
(CT scan) or magnetic resonance imaging (MRI) scan
is considered essential to a quick diagnosis. The MRI
is less sensitive than the CT in detecting acute subarachnoid bleeding, but more sensitive in diagnosing
AVM or aneurysm.
A CT scan reveals blood that has escaped into the
subarachnoid space. For the best results, the scan
should be done within 12 hours of the hemorrhage. If
this is not possible, lumbar puncture and examination
of the cerebrospinal fluid is advised. Lumbar puncture
is also done in cases in which the CT scan doesn’t
reveal a hemorrhage, but there is a high suspicion
that one has occurred. In subarachnoid hemorrhage,
cerebrospinal fluid shows red blood cells and/or
xanthochromia, a yellowish tinge caused by blood
GALE ENCYCLOPEDIA OF MEDICINE

breakdown products. Xanthochromia first appears
six to 12 hours after subarachnoid hemorrhage, making it advisable to delay lumbar puncture until at least
12 hours after the onset of symptoms for a more
definite diagnosis.
Once a hemorrhage, AVM, or aneurysm has been
diagnosed, further tests are done to pinpoint the
damage. The CT scan may be useful in giving the
general location, but cerebral angiography maps out
the exact details. This procedure involves injecting a
special dye into the blood stream. This dye makes
blood vessels visible in x rays of the area.

Treatment
The initial course of treatment focuses on stabilizing the hemorrhage victim. Depending on the individual’s condition, this may involve intubation and
mechanical ventilation, supplemental oxygen, intravenous fluids, and close monitoring of vital signs. If the
person suffers seizures, an anticonvulsant, such as
phenytoin (Dilantin), is administered. Nimodipine, a
calcium channel blocker, may be given to prevent
vasospasm and its complications. Sedatives and medications for pain, nausea, and vomiting are administered as needed.
Once the individual is stabilized, cerebral angiography is done to locate the damaged blood vessel. This
information and the individual’s condition are considered before attempting surgical treatment. Surgery is
necessary to remove the damaged area of the blood
vessel and prevent a second hemorrhage. The specific
neurosurgical procedures depend on the location and
type of blood vessel damage. Typically, clip ligation is
the preferred means of treating an aneurysm, and
surgical excision, radiosurgery, or endovascular embolization are used to manage an AVM.

Prognosis
Individuals who are conscious and demonstrate
few neurologic symptoms when they reach medical
help have the best prognosis. However, the overall
prospects for subarachnoid hemorrhage patients are
generally not good. Of the individuals who suffer an
aneurysmal hemorrhage, approximately 15% do not
live long enough to get medical treatment. Another 2040% will not survive the complications caused by the
hemorrhage, and approximately 12% of the survivors
will experience permanent neurologic disability.
Neurologic disabilities may include partial paralysis,
weakened or numbed areas of the body, cognitive or
speech difficulties, and vision problems. Individuals
3575

Subarachnoid hemorrhage

Causes and symptoms

Subarachnoid hemorrhage

KEY TERMS
Aneurysm—A weak point in a blood vessel where
the pressure of the blood causes the vessel wall to
bulge outwards. An aneurysm may also appear as a
sac-like projection from the blood vessel wall.
Arachnoid mater—One of three membranes that
encase the brain and spinal cord. The arachnoid
mater is the middle membrane.
Arteriovenous malformation—An abnormal tangle
of arteries and veins in which the arteries feed
directly into the veins without a normal intervening
capillary bed.
Atherosclerosis—An abnormal condition in which
lipids, or fats, form deposits on the inside walls of
blood vessels.
Cerebral angiography—A medical test in which an
x-ray visible dye is injected into blood vessels to
allow them to be imaged on an x ray.
Cerebrospinal fluid—The clear, normally colorless
fluid found within the subarachnoid space.

Hemorrhage—The escape of blood from blood
vessels.
Hydrocephalus—Englargement of the chambers in
the brain (ventricles) caused by an accumulation of
cerebrospinal fluid.
Intracranial hypertension—Abnormally high pressure within the brain.
Ischemia—A condition in which blood flow is cut
off or restricted from a particular area. The tissue
becomes starved of oxygen and nutrients, resulting
in tissue death.
Ischemic—Referring to ischemia.
Lumbar puncture—A diagnostic procedure in
which a needle is inserted into the lower spine to
withdraw a small amount of cerebrospinal fluid. This
fluid is examined to assess trauma to the brain.
Subarachnoid—Referring to the space underneath
the arachnoid mater.

Computerized tomography (CT) scan—Crosssectional x rays of the body compiled to create a
three-dimensional image of the body’s internal
structures.

Vasospasm—The constriction or narrowing of blood
vessels. In cases of hemorrhage, the constriction is
prompted by chemical signals from the escaped
blood as it breaks down.

whose subarachnoid hemorrhages occur as a result of
AVMs have a slightly better prognosis, although the
risk of death is approximately 10–15% for each
hemorrhage.

groups, and health-care professionals. These same
groups also advise using seat belts in automobiles.

Subarachnoid hemorrhage associated with traumatic brain injury has a poor prognosis. In clinical
studies, 46–78% of head injury cases involving subarachnoid hemorrhage resulted in severe disability,
vegetative survival, or death. Furthermore, it is possible that traumatic subarachnoid hemorrhages are
accompanied by additional injuries, which would
further diminish survival and recovery rates.

Spontaneous subarachnoid hemorrhages are
more difficult to prevent. Since there may be a genetic
component to aneurysms and AVMs, close relatives to
individuals with these conditions may consider being
screened to assess their own status. Quitting smoking
and keeping blood pressure within normal limits may
also reduce the risk of suffering a spontaneous subarachnoid hemorrhage.
Resources
ORGANIZATIONS

Prevention
Traumatic brain injury is the leading cause of subarachnoid hemorrhages, so it follows that efforts to
prevent head injury would prevent these hemorrhages.
Since accidents cannot always be prevented, measures
to minimize potential damage are always advisable.
Use of activity-appropriate protective gear, such as
bicycle helmets, motorcycle helmets, and sports head
gear, is strongly encouraged and promoted by medical
associations, consumer organizations, advocacy
3576

Brain Injury Association of America. 105 North Alfred St.,
Alexandria, VA 22314. (800) 444-6443. <http://
www.biausa.org>.
National Stroke Association. 9707 E. Easter Lane,
Englewood, Co. 80112. (800) 787-6537. <http://
www.stroke.org>.

Julia Barrett

Subdural empyema see Central nervous
system infections
GALE ENCYCLOPEDIA OF MEDICINE

Subdural hematoma

Subdural hematoma
Definition
A subdural hematoma is a collection of blood
in the space between the outer layer (dura) and
middle layers of the covering of the brain (the
meninges). It is most often caused by torn, bleeding
veins on the inside of the dura as a result of a blow
to the head.

Description
Subdural hematomas most often affect people
who are prone to falling. Only a slight hit on the
head or even a fall to the ground without hitting the
head may be enough to tear veins in the brain, often
without fracturing the skull. There may be no external
evidence of the bruising on the brain’s surface.
Small subdural hematomas may not be very serious, and the blood can be slowly absorbed over several
weeks. Larger hematomas, however, can gradually
enlarge over several weeks, even though the bleeding
has stopped. This enlargement can compress the brain
itself, possibly leading to death if the blood is not
drained.
The time between the injury and the appearance of
symptoms can vary from less than 48 hours to several
weeks, or more. Symptoms appearing in less than 48
hours are due to an acute subdural hematoma. This
type of bleeding is often fatal, and results from tearing
of the venous sinus. If more than two weeks have
passed before symptoms appear, the condition is
called a chronic subdural hematoma, resulting from
tearing of the smaller vein. The young and the old are
most likely to experience a chronic condition. This
chronic form is less risky, as pressure of the veins
against the skull lessens the bleeding. Prompt medical
care can reduce the probability of permanent brain
damage.

Causes and symptoms
A subdural hematoma is caused by an injury
to the head that tears blood vessels. In childhood,
hematomas are a common complication of falls.
A subdural hematoma also may be an indication
of child abuse, as evidenced by shaken baby
syndrome.
Symptoms tend to fluctuate, and include:


headache



episodes of confusion and drowsiness

GALE ENCYCLOPEDIA OF MEDICINE

Subdural hematoma present on autopsied body. (Custom
Medical Stock Photo. Reproduced by permission.)



one-sided weakness or paralysis



lethargy



enlarged or asymmetric pupils



convulsions or loss of consciousness after head
injury



coma

A doctor should be contacted immediately if
symptoms appear. Because these symptoms mimic
the signs of a stroke, the patient should tell the doctor
about any head injury within the previous few months.
In an infant, symptoms may include increased pressure within the skull, growing head size, bulging fontanelle (one of two soft spots on a infant’s skull), vomiting,
irritability, lethargy, and seizures. In cases of child abuse,
there may be fractures of the skull or other bones.

Diagnosis
A chronic subdural hematoma can be difficult to
diagnose, but a slow loss of consciousness after a head
injury is assumed to be a hematoma unless proven
otherwise. The hematoma can be confirmed with magnetic resonance imaging (MRI), which is the preferred
type of scan; a hematoma can be hard to detect on a
computed tomography scan (CT scan), depending on
how long after the hemorrhage the CT is done.

Treatment
Small hematomas that do not cause symptoms
may not need to be treated. Otherwise, the hematoma
should be surgically removed. Liquid blood can be
drained from burr holes drilled into the skull. The
surgeon may have to open a section of skull to remove
a large hematoma or to tie off the bleeding vein.
3577

Substance abuse and dependence

Corticosteroids and diuretics can control brain
swelling. After surgery, anticonvulsant drugs (such as
phenytoin) may help control or prevent seizures,
which can begin as late as two years after the head
injury.

Prognosis
If treatment is provided soon enough, recovery is
usually complete. Headache, amnesia, attention problems, anxiety, and giddiness may continue for some
time after surgery. Most symptoms in adults usually
disappear within six months, with further improvement over several years. Children tend to recover
much faster.

Prevention
Because a subdural hematoma usually follows a
head injury, preventing head injury can prevent a
hematoma.
Resources
ORGANIZATIONS

CT scan indicating subdural hematoma highlighted as a red
mass on the center left of the brain. (Photo Researchers.
Reproduced by permission.)

American Academy of Neurology. 1080 Montreal Ave., St.
Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.
Brain Injury Association of America. 105 North Alfred St.,
Alexandria, VA 22314. (800) 444-6443. <http://
www.biausa.org>.
Head Injury Hotline. P.O. Box 84151, Seattle WA 98124.
(206) 621- 8558. <http://www.headinjury.com>.
Head Trauma Support Project, Inc. 2500 Marconi Ave., Ste.
203, Sacramento, CA 95821. (916) 482-5770.

Carol A. Turkington

Subdural hemorrhage see Subdural
hematoma

KEY TERMS
Corticosteroids—A group of drugs similar to natural corticosteroid hormones produced by the
adrenal glands. The drugs have a wide variety of
applications, including use for inflammatory disorders and swelling.
Diuretics—A group of drugs that helps remove
excess water from the body by increasing the
amount lost by urination.
Fontanelle—One of the two soft areas on a baby’s
scalp; a membrane-covered gap between the
bones of the skull.

3578

Subluxations see Dislocations and
subluxations

Substance abuse and
dependence
Definition
Substance abuse and dependence refer to any continued pathological use of a medication, non-medically indicated drug (called drugs of abuse), or toxin.
They normally are distinguished as follows.
GALE ENCYCLOPEDIA OF MEDICINE

Substance abuse is more likely to be diagnosed
among those who have just begun taking drugs and
is often an early symptom of substance dependence.
However, substance dependence can appear without
substance abuse, and substance abuse can persist for
extended periods of time without a transition to substance dependence.

rape and sexual assault, aggravated assault, robbery,
burglary, and larceny. According to the National
Institute on Alcohol Abuse and Alcoholism
(NIAAA), the estimated cost of alcohol-related disorders alone (including health care expenditures, lost
productivity, and premature death) was $166.5 billion
in 1995.
The term substance, when discussed in the context of substance abuse and dependence, refers to
medications, drugs of abuse, and toxins. These substances have an intoxicating effect, desired by the
user, which can have either stimulating (speeding
up) or depressive/sedating (slowing down) effects
on the body. Substance dependence and/or abuse
can involve any of the following 10 classes of
substances:


alcohol



amphetamines (including ‘‘crystal meth,’’ some medications used in the treatment of attention deficit
disorder [ADD], and amphetamine-like substances
found in appetite suppressants)



cannibis (including marijuana and hashish)



cocaine (including ‘‘crack’’)



hallucinogens (including LSD, mescaline, and
MDMA [‘‘ecstasy’’])



inhalants (including compounds found in gasoline,
glue, and paint thinners)



nicotine (substance dependence only)



opioids (including morphine, heroin, codeine, methadone, oxycodone [Oxycontin (TM)])



phencyclidine
ketamine)



sedative, hypnotic, and anxiolytic (anti-anxiety) substances (including benzodiazepines such as valium,
barbiturates, prescription sleeping medications, and
most prescription anti-anxiety medications)

Description
Substance abuse and dependence are disorders
that affect all population groups although specific
patterns of abuse and dependence vary with age, gender, culture, and socioeconomic status. According to
data from the National Longitudinal Alcohol
Epidemiologic Survey, 13.3% of a survey group of
Americans exhibited symptoms of alcohol dependence
during their lifetime, and 4.4% exhibited symptoms of
alcohol dependence during the past 12 months.
According to the 1997 National Household Survey
on Drug Abuse, 6.4% of those surveyed had used an
illicit drug in the past month.
Although substance dependence can begin at
any age, to people aged 18 to 24 have relatively
high substance use rates, and dependence often
arises sometime during the ages of 20 to 49.
Gender proportions vary according to the class of
drugs, but substance use disorders are in general
more frequently seen in men. A 2004 report revealed
that in a 2002 national survey, more than 2.6 million
youths age 12 to 17 had used inhalants more than
once.
In addition to being an individual health disorder,
substance abuse and dependence may be viewed as a
public health problem with far-ranging health, economic, and adverse social implications. Substancerelated disorders are associated with teen pregnancy
and the transmission of sexually transmitted diseases
(STDs), as well as failure in school, unemployment,
domestic violence, homelessness, and crimes such as
GALE ENCYCLOPEDIA OF MEDICINE

(including

PCP,

angel

dust,

Caffeine has been identified as a substance in this
context, but as yet there is insufficient evidence to
establish whether caffeine-related symptoms fall
under substance abuse and dependence.
Substances of abuse may thus be illicit drugs,
readily available substances such as alcohol or glue,
over-the-counter drugs, or prescription medications.
In many cases, a prescription medication that
becomes a substance of abuse may have been a
legal, medically indicated prescription for the user,
but the pattern of use diverges from the use prescribed by the physician.
3579

Substance abuse and dependence

Substance abuse is any pattern of substance use
that results in repeated adverse social consequences
related to drug-taking—for example, interpersonal
conflicts, failure to meet work, family, or school obligations, or legal problems. Substance dependence,
commonly known as addiction, is characterized by
physiological and behavioral symptoms related to
substance use. These symptoms include the need for
increasing amounts of the substance to maintain
desired effects, withdrawal if drug-taking ceases,
and a great deal of time spent in activities related to
substance use.

Substance abuse and dependence

Frequency Of Substance Abuse By Gender And Age

Men
Ages 18 to 29
Ages 30 to 44
Ages 45 to 64
Over age 65
Women
Ages 18 to 29
Ages 30 to 44
Ages 45 to 64
Over age 65

17 to 24 percent
11 to 14 percent
6 to 8 percent
1 to 3 percent
4 to 10 percent
2 to 4 percent
1 to 2 percent
less than 1 percent

penalties, such as legal or social sanctions, may reduce
the likelihood of substance use.
At the level of neurobiology, it is believed that
substances of abuse operate through similar pathways
in the brain. The chemical changes induced by the
stimulation of these pathways by initial use of the
substance lead to the desire to continue substance
use, and eventual substance dependence.
Symptoms
The DSM-IV-TR identifies seven criteria (symptoms), at least three of which must be met during a
given 12-month period, for the diagnosis of substance
dependence:


Tolerance, as defined either by the need for increasing amounts of the substance to obtain the desired
effect or by experiencing less effect with extended use
of the same amount of the substance.



Withdrawal, as exhibited either by experiencing
unpleasant mental, physiological, and emotional
changes when drug-taking ceases or by using the
substance as a way to relieve or prevent withdrawal
symptoms.



Longer duration of taking substance or use in greater
quantities than was originally intended.



Persistent desire or repeated unsuccessful efforts to
stop or lessen substance use.



A relatively large amount of time spent in securing
and using the substance, or in recovering from the
effects of the substance.



Important work and social activities reduced because
of substance use.



Continued substance use despite negative physical
and psychological effects of use.

Causes and symptoms
Causes
The causes of substance dependence are not well
established, but three factors are believed to contribute to substance-related disorders: genetic factors,
psychopathology, and social learning. In genetic
epidemiological studies of alcoholism, the probability
of identical twins both exhibiting alcohol dependence was significantly greater than with fraternal
twins, thus suggesting a genetic component in alcoholism. It is unclear, however, whether the genetic
factor is related to alcoholism directly, or whether it
is linked to other psychiatric disorders that are
known to be associated with substance abuse. For
example, there is evidence that alcoholic males from
families with depressive disorders tend to have more
severe courses of substance dependence than alcoholic men from families without such family
histories.
These and other findings suggest substance use
may be way to relieve the symptoms of a psychological
disorder. In this model, unless the underlying pathology is treated, attempts to permanently stop substance
dependence are ineffective. Psychopathologies that
are associated with substance dependence include
antisocial personality disorder, bipolar disorder,
depression, anxiety disorder, and schizophrenia.
A third factor related to substance dependence is
social environment. In this model, drug-taking is
essentially a socially learned behavior. Local social
norms determine the likelihood that a person is
exposed to the substance and whether continued use
is reinforced. For example, individuals may, by observing family or peer role models, learn that substance
use is a normal way to relieve daily stresses. External
3580

Although not explicitly listed in the DSM-IV-TR
criteria, ‘‘craving,’’ or the overwhelming desire to use
the substance regardless of countervailing forces, is a
universally-reported
symptom
of
substance
dependence.
Symptoms of substance abuse, as specified by
DSM-IV-TR, include one or more of the following
occurring during a given 12-month period:


Substance use resulting in a recurrent failure to fulfill
work, school, or home obligations (work absences,
substance-related school suspensions, neglect of
children).



Substance use in physically hazardous situations
such as driving or operating machinery.
GALE ENCYCLOPEDIA OF MEDICINE

Substance use resulting in legal problems such as
drug-related arrests.



Continued substance use despite negative social and
relationship consequences of use.

In addition to the general symptoms, there are
other physical signs and symptoms of substance
abuse that are related to specific drug classes:


Signs and symptoms of alcohol intoxication include
such physical signs as slurred speech, lack of coordination, unsteady gait, memory impairment, and
stupor, as well as behavior changes shortly after
alcohol ingestion, including inappropriate aggressive behavior, mood volatility, and impaired
functioning.



Amphetamine users may exhibit rapid heartbeat,
elevated or depressed blood pressure, dilated
(enlarged) pupils, weight loss, as well as excessively
high energy, inability to sleep, confusion, and occasional paranoid psychotic behavior.



Cannibis users may exhibit red eyes with dilated
pupils, increased appetite, dry mouth, and rapid
pulse; they may also be sluggish and slow to react.



Cocaine users may exhibit rapid heart rate, elevated
or depressed blood pressure, dilated pupils, weight
loss, in addition to wide variations in their energy
level, severe mood disturbances, psychosis, and
paranoia.



Users of hallucinogens may exhibit anxiety or
depression, paranoia, and unusual behavior in
response to hallucinations (imagined sights, voices,
sounds, or smells that appear real). Signs include
dilated pupils, rapid heart rate, tremors, lack of coordination, and sweating. Flashbacks, or the re-experiencing of a hallucination long after stopping
substance use, are also a symptom of hallucinogen
use.



Users of inhalants experience dizziness, spastic eye
movements, lack of coordination, slurred speech,
and slowed reflexes. Associated behaviors may
include belligerence, tendency toward violence,
apathy, and impaired judgment.



Opioid drug users exhibit slurred speech, drowsiness,
impaired memory, and constricted (small) pupils.
They may appear slowed in their physical
movements.



Phencyclidine users exhibit spastic eye movements,
rapid heartbeat, decreased sensitivity to pain, and
lack of muscular coordination. They may show belligerence, predisposition to violence, impulsiveness,
and agitation.

GALE ENCYCLOPEDIA OF MEDICINE



Users of sedative, hypnotic, or anxiolytic drugs
show slurred speech, unsteady gait, inattentiveness,
and impaired memory. They may display inappropriate behavior, mood volatility, and impaired
functioning.

Other signs are related to the form in which the
substance is used. For example, heroin, certain other
opioid drugs, and certain forms of cocaine may be
injected. A person using an injectable substance may
have ‘‘track marks’’ (outwardly visible signs of the site
of an injection, with possible redness and swelling of
the vein in which the substance was injected).
Furthermore, poor judgment brought on by substance
use can result in the injections being made under
dangerously unhygienic conditions. These unsanitary
conditions and the use of shared needles are risk
factors for major infections of the heart, as well as
infection with HIV (the virus that causes AIDS), certain forms of hepatitis (a liver infection), and
tuberculosis.
Cocaine is often taken as a powdery substance
which is ‘‘snorted’’ through the nose. This can result
in frequent nosebleeds, sores in the nose, and even
erosion (an eating away) of the nasal septum (the
structure that separates the two nostrils).
Overdosing on a substance is a frequent complication of substance abuse. Drug overdose can be purposeful (with suicide as a goal), or due to carelessness, the
unpredictable strength of substances purchased from
street dealers, mixing of more than one type of substance, or as a result of the increasing doses that a
person must take to experience intoxicating effects.
Substance overdose can be a life-threatening emergency, with the specific symptoms depending on the
type of substance used. Substances with depressive
effects may dangerously slow the breathing and heart
rate, drop the body temperature, and result in a general unresponsiveness. Substances with stimulatory
effects may dangerously increase the heart rate and
blood pressure, produce abnormal heart rhythms,
increase body temperature, induce seizures, and
cause erratic behavior.

Diagnosis
Tools used in the diagnosis of substance dependence include screening questionnaires and patient
histories, physical examination, and laboratory tests.
A simple and popular screening tool is the CAGE
questionnaire. CAGE refers to the first letters of
each word that forms the basis of each of the four
questions of the screening exam:
3581

Substance abuse and dependence



Substance abuse and dependence

PULMONARY
"Narcotic lung"
Talc granulomas

RENAL
Glomerulopathy

BRAIN
Overdose
Coma
Hallucinations

INFECTIONS
Bacterial endocarditis
Viral hepatitis
AIDS (lymph nodes)

LOCAL
Abscesses
Cellulitis
Ulcers
Thrombosed veins

Substance abuse often causes a variety of medical abnormalities and conditions throughout the body, as shown in the
illustration above. (Illustration by Electronic Illustrators Group.)



Have you ever tried to Cut down on your substance
use?



Have you ever been Annoyed by people trying to talk
to you about your substance use?



Do you ever feel Guilty about your substance use?



Do you ever need an Eye opener (use of the substance
first thing in the morning) in order to start your day?

A ‘‘yes’’ answer to two or more of these questions
is an indication that the individual should be referred
for more thorough work-up for substance dependency
or abuse.
In addition to CAGE, other screening questionnaires are available. Some are designed for particular
population groups such as pregnant women, and
others are designed to more thoroughly assess the
severity
of
substance
dependence.
These
3582

questionnaires, known by their acronyms, include
AUDIT, HSS, HSQ, PRIME-MD, ACE, TWEAK,
s-MAST, and SADD. There is some variability among
questionnaires in terms of how accurately and comprehensively they can identify individuals as substance
dependent.
Patient history, as taken through the direct interview, is important for identifying physical symptoms
and psychiatric factors related to substance use.
Family history of alcohol or other substance dependency is also useful for diagnosis.
A physical examination may reveal signs of substance abuse. These signs are specific to the substances
used, as well as needle marks, tracks, or nasal erosion.
With the individual’s permission, substance use
can be detected through laboratory testing of his or
her blood, urine, or hair. Laboratory testing, however,
GALE ENCYCLOPEDIA OF MEDICINE

One of the most difficult aspects of diagnosis
involves overcoming the patient’s denial. Denial is a
psychological state during which a person is unable to
acknowledge the (usually negative) circumstances of a
situation. In this case, denial leads a person to underestimate the degree of substance use and of the problems associated with substance use.

Treatment
According to the American Psychiatric
Association, there are three goals for the treatment of
people with substance use disorders: (1) the patient
abstains from or reduces the use and effects of the substance; (2) the patient reduces the frequency and severity
of relapses; and (3) the patient develops the psychological and emotional skills necessary to restore and maintain personal, occupational, and social functioning.
In general, before treatment can begin, many
treatment centers require that the patient undergo
detoxification. Detoxification is the process of weaning the patient from his or her regular substance use.
Detoxification can be accomplished ‘‘cold turkey,’’ by
complete and immediate cessation of all substance use,
or by slowly decreasing (tapering) the dose which a
person is taking, to minimize the side effects of withdrawal. Some substances must be tapered because
‘‘cold turkey’’ methods of detoxification are potentially life threatening. In some cases, medications
may be used to combat the unpleasant and threatening
physical and psychological symptoms of withdrawal.
For example, methadone is used to help patients
adjust to the tapering of heroin use.
Treatment itself consists of three parts: (1) assessment; (2) formulation of a treatment plan; (3) psychiatric management. The first step in treatment is a
comprehensive medical and psychiatric evaluation of
the patient. This evaluation includes:


a history of the patient’s past and current substance
use, and its cognitive, psychological, physiological,
and behavioral effects



a medical and psychiatric history and examination



a history of psychiatric treatments and outcomes



a family and social history



screening of blood, breath, or urine for substances



other laboratory tests to determine the presence of
other conditions commonly found with substance
use disorders

GALE ENCYCLOPEDIA OF MEDICINE

After the assessment is made, a treatment plan is
formulated. Treatment plans vary according to the
needs of the specific patient and can change for the
same patient as he or she undergoes different phases of
the disorder. Plans typically involve the following elements: (1) a strategy for the psychiatric management
of the patient; (2) a strategy for reducing effects or use
of substances, or for abstinence; (3) efforts to ensure
compliance with the treatment program and to prevent relapse; (4) treatments for other conditions associated with substance use. Initial therapy and
treatment setting (hospital, residential treatment, partial hospitalization, outpatient) decisions are made as
part of the treatment plan, but because substance use
disorders are considered a chronic condition requiring
long-term care, these plans can and do change through
the course of treatment.
The third step, psychiatric management of the
patient, is the implementation of the treatment plan.
Psychiatric management of the patient includes
establishing a trusting relationship between clinician
and patient; monitoring the patient’s progress;
managing the patient’s relapses and withdrawal;
diagnosing and treating associated psychiatric disorders; and helping the patient adhere to the treatment
plan through therapy and the development of skills
and social interactions that reinforce a drug-free
lifestyle.
As part of the treatment process, patients typically
undergo psychosocial therapy and, in some cases,
pharmacologic treatment. Psychosocial therapeutic
modalities include cognitive-behavioral therapy, behavioral therapy, individual psychodynamic or interpersonal therapy, group therapy, family therapy, and selfhelp groups. Pharmacologic treatment may include
medications that ease withdrawal symptoms, reduce
craving, interact negatively with substances of abuse
to discourage drug-taking, or treat associated psychiatric disorders.

Alternative treatment
The efficacy of alternative treatments for substance use disorders remains for the most part ambiguous. One treatment that has been recently shown to
have variable success is the use of acupuncture in treating substance dependence. In 2000, a randomized controlled trial of the effect of acupuncture on cocaine
addiction reported that acupuncture significantly
reduced the cocaine use of study participants. A 1999
meta-analysis (summary analysis of studies), however,
reported that acupuncture had no statistically significant effect on smoking cessation.
3583

Substance abuse and dependence

may be limited by the sensitivity and specificity of the
testing method, and by the time elapsed since the
person last used the drug.

Substance abuse and dependence

There has been movement toward examining some
touted treatments in more rigorous clinical trials. In
particular, there has been some interest in Pueraria
lobata, or kudzu, an herb that has reputedly been used
in Chinese medicine to treat alcoholism. Preclinical trials
of an herbal formula with kudzu have shown that
increased consumption of the herbal formula is associated with decreased consumption of alcohol. Toxicity
studies show few ill effects of the formula, and human
trials are currently being undertaken to more fully evaluate the efficacy of this treatment.
The effectiveness of electroacupuncture (the practice of acupuncture accompanied by the application of
low levels of electrical current at acupuncture points)
in alleviating opiate withdrawal symptoms is also
being examined. Preclinical trials suggest that electroacupuncture treatment given prior to the administration of naxolone seems to alleviate the withdrawal
effects of naxolone.

Prognosis
Recovery from substance use is notoriously difficult, even with exceptional treatment resources.
Although relapse rates are difficult to accurately
obtain, the NIAAA cites evidence that 90% of alcohol
dependent users experience at least one relapse within
the 4 years after treatment. Relapse rates for heroin
and nicotine users are believed to be similar. Certain
pharmacological treatments, however, have been
shown to reduce relapse rates.
Relapses are most likely to occur within the first 12
months of having discontinued substance use. Triggers
for relapses can include any number of life stresses (problems on the job or in the marriage, loss of a relationship,
death of a loved one, financial stresses), in addition to
seemingly mundane exposure to a place or an acquaintance associated with previous substance use.
The development of adaptive life skills and
ongoing drug-free social support are believed to be
two important factors in avoiding relapse. The effect
of the support group Alcoholics Anonymous has been
intensively studied, and a 1996 meta-analysis noted
that long-term sobriety appears to be positively
related to Alcoholics Anonymous attendance and
involvement. Support for family members in addition
to support for the individual in recovery is also important. Because substance dependence has a serious
impact on family functioning, and because family
members may inadvertently maintain behaviors that
initially led to the substance dependence, ongoing
therapy and support for family members should not
be neglected.
3584

KEY TERMS
Addiction—The state of being both physically and
psychologically dependent on a substance.
Dependence—A state in which a person
requires a steady concentration of a particular
substance to avoid experiencing withdrawal
symptoms.
Detoxification—A process whereby an addict is
withdrawn from a substance.
Intoxication—The desired mental, physical, or
emotional state produced by a substance.
Street drug—A substance purchased from a drug
dealer; may be a legal substance, sold illicitly
(without a prescription, and not for medical use),
or it may be a substance that is illegal to possess.
Tolerance—A phenomenon whereby a drug user
becomes physically accustomed to a particular
dose of a substance, and requires increasing
dosages in order to obtain the same effects.
Withdrawal—Those side effects experienced by a
person who has become physically dependent on a
substance, upon decreasing the substance’s dosage
or discontinuing its use.

Prevention
Prevention is best aimed at teenagers and young
adults aged 18–24 who are at very high risk for substance experimentation. Prevention programs should
include an education component that outlines the risks
and consequences of substance use and a training
component that gives advice on how to resist peer
pressure to use drugs.
Furthermore, prevention programs should work
to identify and target children who are at relatively
higher risk for substance abuse. This group includes
victims of physical or sexual abuse, children of parents
who have a history of substance abuse, and children
with poor school performance and/or attention deficit
disorder. These children may require more intensive
intervention.
Resources
BOOKS

American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed., revised.
Washington, DC: American Psychiatric Association,
2000.

GALE ENCYCLOPEDIA OF MEDICINE

‘‘Inhalant Abuse Becomes Focus of SAMHSA Guidelines,
Prevention Effors.’’ Alcoholism &Drug Abuse Weekly
March 22, 2004: 1–4.
Schneider, Robert K., James L. Levenson, and Sidney H.
Schnoll. ‘‘Update in Addiction Medicine.’’ Annals of
Internal Medicine 134 (March 6, 2001): 387-395.

Genevieve Pham-Kanter
Teresa G. Odle

Substance dependence see Substance abuse
and dependence
Sucralfate see Antiulcer drugs
Sucrose intolerance see Carbohydrate
intolerance

Sudden cardiac death
Definition
Sudden cardiac death (SCD) is an unexpected
death due to heart problems, which occurs within
one hour from the start of any cardiac-related symptoms. SCD is sometimes called cardiac arrest.

Description
When the heart suddenly stops beating effectively
and breathing ceases, a person is said to have experienced sudden cardiac death.
SCD is not the same as actual death. In actual
death, the brain also dies. The important difference is
that sudden cardiac death is potentially reversible. If it
is reversed quickly enough, the brain will not die.
Sudden cardiac death is also not the same as a
heart attack. A heart attack (myocardial infarction) is
the result of a blockage in an artery which feeds the
heart, so the heart becomes starved for oxygen. The
part that has been starved is damaged beyond repair,
but the heart can still beat effectively.

KEY TERMS
Defibrillator—A device which delivers a controlled electric shock to the heart to return it to
normal beating rhythm.
Ventricular fibrillation—When The lower chamber of the heart quivers instead of pumping in an
organized way.
Ventricular tachycardia—A rapid heartbeat,
usually over 100 beats per minute.

cardiac death. The risk for SCD is higher for anyone
with heart disease.
When the heart stops beating effectively and the
brain is being deprived of oxygenated blood, a medical
emergency exists.

Diagnosis
Diagnosis of sudden cardiac death is made when
there is a sudden loss of consciousness, breathing
stops, and there is no effective heart beat.

Treatment
When sudden cardiac death occurs, the first priority
is to establish the flow of oxygenated blood to the brain.
The next priority is to restore normal rhythm to the
heart. Forcing air into the mouth will get oxygen into
the lungs. Compressing the chest simulates a pumping
heart and will get some blood flow to the lungs, brain,
and coronary arteries. This method is called cardiopulmonary resuscitation (CPR). When trained help arrives,
they will attempt to establish a normal heart beat by
using a device called a defibrillator.
When If sudden cardiac death occurs outside the
hospital setting, cardiopulmonary resuscitation (CPR)
must begin within four to six minutes and advanced
life support measures must begin within eight minutes,
to avoid brain death. CPR requires no special medical
skills and training is available for the ordinary person
nationwide.

Causes and symptoms
Sudden cardiac death is usually caused by ventricular fibrillation (the lower chamber of the heart quivers instead of pumping in an organized rhythm).
Ventricular fibrillation almost never returns to normal
by itself, so the condition requires immediate intervention. Ventricular tachycardia can also lead to sudden
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Sudden cardiac death is reversible in most people
if treatment is begun quickly. However, of the people
who are resuscitated, 40% will have another SCD
within two years if they do not receive appropriate
treatment for the underlying cause of the episode.
3585

Sudden cardiac death

PERIODICALS

Sudden infant death syndrome

Prevention
Ten Leading Causes Of Infant Death (U.S.)

When In order to prevent sudden cardiac death,
underlying heart conditions must be addressed.
Medications and implantable cardioverter-defibrillators may be used.

Congenital anomalies
Pre-term/Low birthweight
Sudden Infant Death Syndrome (SIDS)
Respiratory Distress Syndrome
Problems related to complications of pregnancy
Complications of placenta, cord, and membrane Accidents
Perinatal infections
Pneumonia/Influenza
Intrauterine hypoxia and birth asphyxia

Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas, TX
75231. (214) 373-6300. <http://www.americanheart.org>.

Dorothy Elinor Stonely



sleeping on the stomach (in the prone position)



mother who smokes during pregnancy; smokers are
as much as three times more likely than nonsmokers
to have a SIDS baby



the presence of passive smoke in the household



male sex; the male/female ratio in SIDS deaths is 3:2;



belonging to an economically deprived or minority
family



mother under 20 years of age at pregnancy



mother who abuses drugs



mother with little or no prenatal care



prematurity or low weight at birth



family history of SIDS

Sudden infant death syndrome
Definition
Sudden infant death syndrome (SIDS) is the unexplained death without warning of an apparently
healthy infant, usually during sleep.

Description
Also known as crib death, SIDS has baffled physicians and parents for years. In the 1990s, advances have
been made in preventing the occurrence of SIDS, which
killed more than 4,800 babies in 1992 and 3,279 infants in
1995. Education programs aimed at encouraging parents and caregivers to place babies on their backs and
sides when putting them to bed have helped contribute to
a lower mortality rate from SIDS.
In the United States, SIDS strikes one or two infants
in every thousand, making it the leading cause of death
in newborns. It accounts for about 10% of deaths occurring during the first year of life. SIDS most commonly
affects babies between the ages of two months and six
months; it almost never strikes infants younger than two
weeks of age or older than eight months. Most SIDS
deaths occur between midnight and 8 A.M.

Causes and symptoms
Risk factors for SIDS
The exact causes of SIDS are still unknown,
although studies have shown that many of the infants
had recently been under a doctor’s care for a cold or
other illness of the upper respiratory tract. Most SIDS
deaths occur during the winter and early spring, which
are the peak times for respiratory infections. The most
common risk factors for SIDS include:
3586

Most of these risk factors are associated with significantly higher rates of SIDS; however, none of them
are exact enough to be useful in predicting which
specific children may die from SIDS.
Theories about SIDS
MEDICAL DISORDERS. Currently, it is not known
whether the immediate cause of death from SIDS is a
heart problem or a sudden interruption of breathing.
The most consistent autopsy findings are pinpoint
hemorrhages inside the baby’s chest and mild inflammation or congestion of the nose, throat, and airway.
Some doctors have thought that the children stop
breathing because their upper airway gets blocked.
Others have suggested that the children have an
abnormally high blood level of the chemicals that
transmit nerve impulses to the brain, or that there is
too much fetal hemoglobin in the blood. A third theory concerns the possibility that SIDS infants have an
underlying abnormality in the central nervous system.
This suggestion is based on the assumption that normal infants sense when their air supply is inadequate
and wake up. Babies with an abnormal nervous

GALE ENCYCLOPEDIA OF MEDICINE

Congenital—Existing or present at the time of birth.

the case rate. The following are recommended as
preventive measures:


Sleep position. The United States Department of
Health and Human Services initiated a ‘‘Back-toSleep’’ campaign in 1994 to educate the public
about sleep position. Prior to that time, an estimated
70% of infants slept on their stomachs, since parents
had been taught that a ‘‘back down’’ position contributed to choking during sleep. There are some
conditions for which doctors will recommend the
prone position, but for normal infants, side or back
(supine) positions are better. When placing an infant
on his or her side, the parent should pull the child’s
lower arm forward so that he or she is less likely to
roll over onto the stomach. When babies are awake
and being observed, they should be placed on their
stomachs frequently to aid in the development of the
muscles and skills involved in lifting the head. Once a
baby can roll over to his or her stomach, he or she has
developed to the point where the risk of SIDS is
minimal.



Good prenatal care. Proper prenatal care can help
prevent the abnormalities that put children at higher
risk for SIDS. Mothers who do not receive prenatal
care are also more likely to have premature and low
birth-weight babies. Expectant mothers should also
be warned about the risks of smoking, alcohol intake,
and drug use during pregnancy.



Proper bedding. Studies have shown that soft bedding,
such as beanbags, waterbeds and soft mattresses, contributes to SIDS. Babies should sleep on firm mattresses with no soft or fluffy materials underneath or
around them– including quilts, pillows, thick comforters or lambskin. Soft stuffed toys should not be placed
in the crib while babies sleep.



Room temperature. Although babies should be kept
warm, they do not need to be any warmer than is
comfortable for the caregiver. An overheated baby is
more likely to sleep deeply, perhaps making it more
difficult to wake when short of breath. Room temperature and wrapping should keep the baby warm
and comfortable but not overheated.



Diet. Some studies indicate that breastfed babies are
at lower risk for SIDS. It is thought that the mother’s
milk may provide additional immunity to the infections that can trigger sudden death in infants.



Bedsharing with parents. Opinions differ on whether
or not bedsharing of infant and mother increases or
decreases the risk of SIDS. Bedsharing may encourage breastfeeding or alter sleep patterns, which
could lower the risk of SIDS. On the other hand,
some studies suggest that bedsharing increases the

Crib death—Another name for SIDS.
Prone—Lying on the stomach with the face
downward.
Supine—Lying on the back with the face upward.

system, however, do not have the same alarm mechanism in their brains. Other theories about the cause of
death in SIDS include immune system disorders that
cause changes in the baby’s heart rate and breathing
patterns during sleep, or a metabolic disorder that
causes a buildup of fatty acids in the baby’s system.
PHYSICAL SURROUNDINGS. A recent theory proposes that SIDS is connected to the child’s rebreathing
of stale air trapped in soft bedding. In addition to the
infant’s sleeping in the prone position, pillows, sheepskins, and other soft items may contribute to trapping
air around the baby’s mouth and nose, which causes
the baby to breathe in too much carbon dioxide and
not enough oxygen. Wrapping a baby too warmly has
also been proposed as a factor.

Diagnosis
The diagnosis of SIDS is primarily a diagnosis of
exclusion. This means that it is given only after other
possible causes of the baby’s death have been ruled out.
Known risk factors aid in the diagnosis. Unlike the pattern in other diseases, however, the diagnosis of SIDS can
only be given post-mortem. It is recommended that all
infants who die in their sleep receive an autopsy to determine the cause. Autopsies indicate a definite explanation
in about 20% of cases of sudden infant death. In addition,
an autopsy can often put to rest any doubts the parents
may have. Investigation of the location of the death is also
useful in determining the child’s sleeping position, bedding, room temperature, and similar factors.

Treatment
There is no treatment for SIDS, only identification of risk factors and preventive measures. The
baby’s parents may benefit from referral to counseling
and support groups for parents of SIDS victims.

Prevention
SIDS appears to be at least partly preventable,
which has been shown by a substantial decrease in
GALE ENCYCLOPEDIA OF MEDICINE

3587

Sudden infant death syndrome

KEY TERMS

Suicide

risk of SIDS. In any case, mothers who choose to
bring their babies to bed should observe the following cautions: Soft sleep surfaces, as well as quilts,
blankets, comforters or pillows should not be placed
under the baby. Parents who sleep with their infants
should not smoke around the baby, or use alcohol or
other drugs which might make them difficult to
arouse. Parents should also be aware that adult
beds are not built with the same safety features as
infant cribs.


Secondhand smoke. It is as important to keep the
baby’s environment smoke-free during infancy as it
was when the mother was pregnant with the baby.



Electronic monitoring. Electronic monitors are
available for use in the home. These devices sound
an alarm for the parents if the child stops breathing.
There is no evidence, however, that these monitors
prevent SIDS. In 1986, experts consulted by the
National Institutes of Health (NIH) recommended
monitors only for infants at risk. These infants
include those who have had one or more episodes
of breath stopping; premature infants with breathing
difficulties; and babies with two or more older siblings that died of SIDS. Parents who use monitors
should know how to use them properly and what to
for the baby if the alarm goes off.



Immunizations. There is no evidence that immunizations increase the risk of SIDS. In fact, babies who
receive immunizations on schedule are less likely to
die of SIDS.

Resources
ORGANIZATIONS

Association of SIDS and Infant Mortality Programs. MN
SID Center, Children’s Hospitals and Clinics, 2525
Chicago Ave. So., Minneapolis, MN 55404. (612) 8136285. <http://www.asip1.org>.
National Institute of Child Health and Human
Development. Bldg 31, Room 2A32, MSC 2425, 31
Center Drive, Bethesda, MD 20892-2425. (800) 5052742. <http://www.nichd.nih.gov/sids/sids.htm>.
National SIDS Resource Center. 2070 Chain Bridge Road,
Suite 450, Vienna, VA 22181. (703) 821-8955. <http://
www.circsol.com/SIDS/>.
Sudden Infant Death Syndrome Alliance. 1314 Bedford
Avenue, Suite 210, Baltimore, MD 21208. (800) 2217437. <http://www.sidsalliance.org>.

Teresa Odle

Sugar diabetes see Diabetes mellitus
Sugar intolerance see Carbohydrate
intolerance
3588

Suicide
Definition
Suicide is defined as the intentional taking of
one’s own life. Prior to the late nineteenth century,
suicide was legally defined as a criminal act in most
Western countries. In the social climate of the early
2000s, however, suicidal behavior is most commonly
regarded and responded to as a psychiatric
emergency.

Description
Suicide is considered a major public health problem around the world as well as a personal tragedy.
According to the National Institute of Mental Health
(NIMH), suicide was the eleventh leading cause of
death in the United States in 2000, and the third leading cause of death for people between the ages of 15
and 24. About 10.6 out of every 100,000 persons in the
United States and Canada die by their own hands.
There are five suicide victims for every three homicide
deaths in North America as of the early 2000s. There
are over 30,000 suicides per year in the United States,
or about 86 per day; and each day about 1900 people
attempt suicide.
The demographics of suicide vary considerably
within Canada and the United States, due in part to
differences among age groups and racial groups, and
between men and women. Adult males are three to
five times more likely to commit suicide than females,
but females are more likely to attempt suicide. Most
suicides occur in persons below the age of 40; however, elderly Caucasians are the sector of the population with the highest suicide rate. Americans over the
age of 65 accounted for 18 percent of deaths by
suicide in the United States in 2000. Geographical
location is an additional factor; according to the
Centers for Disease Control and Prevention (CDC),
suicide rates in the United States are slightly higher
than the national average in the western states, and
somewhat lower than average in the East and the
Midwest.
Race is also a factor in the demographics of suicide. Between 1979 and 1992, Native Americans had a
suicide rate 1.5 times the national average, with young
males between 15 and 24 accounting for 64% of
Native American deaths by suicide. Asian American
women have the highest suicide rate among all women
over the age of 65. And between 1980 and 1996 the
suicide rate more than doubled for black males
between the ages of 15 and 19.
GALE ENCYCLOPEDIA OF MEDICINE

schizophrenia; and 5–10% for borderline and certain
other personality disorders.

Causes
Suicide is a complex act that represents the end
result of a combination of factors in any individual.
These factors include biological vulnerabilities, life
history, occupation, present social circumstances,
and the availability of means for committing suicide.
While these factors do not ‘‘cause’’ suicide in the strict
sense, some people are at greater risk of self-harm than
others. Risk factors for suicide include:


Male sex.



Age over 75.



A family history of suicide.



A history of previous suicide attempts.



A history of abuse in childhood.



A local cluster of recent suicides or a local landmark
associated with suicides. Examples of the latter
include the Golden Gate Bridge in San Francisco;
Sydney Harbor Bridge in Australia; St. Peter’s
Basilica in Rome; the Eiffel Tower in Paris; Prince
Edward Viaduct in Toronto; and Mount Mihara, a
volcano in Japan.



Recent stressful events: separation or divorce, job
loss, bankruptcy, upsetting medical diagnosis,
death of spouse.



Medical illness. Persons in treatment for such serious
or incurable diseases as AIDS, Parkinson’s disease,
and certain types of cancer are at increased risk of
suicide.



Employment as a police officer, firefighter, physician, dentist, or member of another high-stress
occupation.



Presence of firearms in the house. Death by firearms
is the most common method for women as well as
men as of the early 2000s. In 2001, 55% of reported
suicides in the United States were committed with
guns.





Alcohol or substance abuse. Mood-altering substances are a factor in suicide because they weaken
a person’s impulse control.
Presence of a psychiatric illness. Over 90% of
Americans who commit suicide have a significant
mental illness. Major depression accounts for 60%
(especially in the elderly), followed by schizophrenia,
alcoholism, substance abuse, borderline personality
disorder, Huntington’s disease, and epilepsy. The
lifetime mortality due to suicide in psychiatric
patients is 15% for major depression; 20% for bipolar disorder; 18% for alcoholism; 10% for

GALE ENCYCLOPEDIA OF MEDICINE

Neurobiological factors may also influence a person’s risk of suicide. Post-mortem studies of the brains
of suicide victims indicate that the part of the brain
associated with aggression and other impulsive behaviors (the frontal cortex) has a significantly lower level
of serotonin, a neurotransmitter associated with mood
disorders. Low serotonin levels are correlated with
major depression. In addition, suicide victims have
higher than normal levels of cortisol, a hormone produced in stressful situations, in the tissues of their
central nervous system. Other research has indicated
that abuse in childhood may have permanent effects
on the level of serotonin in the brain, possibly ‘‘resetting’’ the level abnormally low. In addition, twin studies have suggested that there may be a genetic
susceptibility to both suicidal ideation and suicide
attempts which cannot be explained by inheritance of
common psychiatric disorders.
Some psychiatrists propose psychodynamic
explanations of suicide. According to one such theory,
suicide is ‘‘murder in the 180th degree’’ that is, the
suicidal person really wants to kill someone else but
turns the anger against the self instead. Another version of this idea is that the suicidal person has incorporated the image of an abusive parent or other
relative in their own psyche and then tries to eliminate
the abuser by killing the self.

Diagnosis
When a person consults a doctor because they are
thinking of committing suicide, or they are taken to a
doctor’s office or emergency room after a suicide
attempt, the doctor will evaluate the patient’s potential for acting on their thoughts or making another
attempt. The physician’s assessment will be based on
several different sources of information:


The patient’s history, including a history of previous
attempts or a family history of suicide.



A clinical interview in which the physician will ask
whether the patient is presently thinking of suicide;
whether they have made actual plans to do so;
whether they have thought about the means; and
what they think their suicide will accomplish. These
questions help in evaluating the seriousness of the
patient’s intentions.



A suicide note, if any.



Information from friends, relatives, or first responders who may have accompanied the patient.
3589

Suicide

Causes & symptoms

Suicide





Short self-administered psychiatric tests that screen
people for depression and suicidal ideation. The
most commonly used screeners are the Beck
Depression Inventory (BDI), the Depression
Screening Questionnaire, and the Hamilton
Depression Rating Scale.
The doctor’s own instinctive reaction to the
patient’s mood, appearance, vocal tone, and similar
factors.

Treatment of attempted suicide
Suicide attempts range from well-planned
attempts involving a highly lethal method (guns, certain types of poison, jumping from high places, throwing oneself in front of trains or subway cars) that fail
by good fortune to impulsive or poorly planned
attempts using a less lethal method (medication overdoses, cutting the wrists). Suicide attempts at the less
lethal end of the spectrum are sometimes referred to as
suicide gestures or pseudocide. These terms should not
be taken to indicate that suicide gestures are only
forms of attention-seeking; they should rather be
understood as evidence of serious emotional and mental distress.
A suicide attempt of any kind is treated as a
psychiatric emergency by the police and other rescue personnel. Treatment in a hospital emergency
room includes a complete psychiatric evaluation; a
mental status examination; blood or urine tests if
alcohol or drug abuse is suspected; and a detailed
assessment of the patient’s personal circumstances
(occupation, living situation, family or friends
nearby, etc.). The patient will be kept under observation while decisions are made about the need for
hospitalization.
A person who has attempted suicide can be
legally hospitalized against his or her will if he or
she seems to be a danger to the self or others. The
doctor will base decisions about hospitalization on
the severity of the patient’s depression; the availability of friends, relatives, or other social support;
and the presence of other suicide risk factors,
including a history of previous suicide attempts,
substance abuse, and psychosis (loss of contact
with reality, often marked by delusions and hallucinations). If the attempt is judged to be a nonlethal
suicide gesture, the patient may be released after
the psychiatric assessment is completed. According
to CDC figures, 132,353 Americans were hospitalized in 2002 following suicide attempts while
116,639 were released following emergency room
treatment.
3590

Related issues
Survivors of suicide
One group of people that is often overlooked in
discussions of suicide is the friends and family left
behind by the suicide. It is estimated that each person
who kills him- or herself leaves six survivors to deal
with the aftermath; thus there are at least 4.5 million
survivors of suicide in the United States. In addition to
the grief that ordinarily accompanies death, survivors
of suicide often struggle with feelings of guilt and
shame as well. They often benefit from group or individual psychotherapy in order to work through such
issues as wondering whether they could have prevented the suicide or whether they are likely to commit
suicide themselves. The American Foundation for
Suicide Prevention (AFSP) has a number of online
resources available for survivors of suicide.
Assisted suicide
One question that has been raised in developed
countries as the average life expectancy increases is the
legalization of assisted suicide for persons suffering
from a painful terminal illness. Physician-assisted suicide has become a topic of concern since it was legalized in the Netherlands in 2001 and in the state of
Oregon in 1997. It is important to distinguish between
physician-assisted suicide and euthanasia, or ‘‘mercy
killing.’’. Assisted suicide, which is often called ‘‘selfdeliverance’’ in Britain, refers to a person’s bringing
about his or her own death with the help of another
person. Because the other person is often a physician,
the act is often called ‘‘doctor-assisted suicide.’’
Euthanasia strictly speaking means that the physician
or other person is the one who performs the last act
that causes death. For example, if a physician injects a
patient with a lethal overdose of a pain-killing medication, he or she is performing euthanasia. If the physician leaves the patient with a loaded syringe and the
patient injects himself or herself with it, the act is an
assisted suicide. As of early 2005 assisted suicide is
illegal everywhere in the United States except for
Oregon, and euthanasia is illegal in all fifty states.
Media treatment of suicide
The Centers for Disease Control and Prevention
(CDC) sponsored a national workshop in April 1994
that addressed the connection between sensationalized
media treatments of suicide and the rising rate of
suicide among American youth. The CDC and the
American Association of Suicidology subsequently
adopted a set of guidelines for media coverage of
GALE ENCYCLOPEDIA OF MEDICINE

The CDC guidelines point out that the following
types of reporting may increase the risk of ‘‘copycat’’
suicides:


Presenting oversimplified explanations of suicide,
when in fact many factors usually contribute to a
person’s decision to take their own life.



Excessive or repetitive local news coverage.



Sensationalizing the suicide by inclusion of morbid
details or dramatic photographs.



Giving ‘‘how-to’’ descriptions of the method of
suicide.



Describing suicide as an effective coping strategy or
as a way to achieve certain goals.



Glorifying the act of suicide or the person who commits suicide.

Alternative treatment
Some alternative treatments may help to prevent
suicide by preventing or relieving depression.
Meditation practice or religious faith and worship
have been shown to lower a person’s risk of suicide.
In addition, any activity that brings people together in
groups and encourages them to form friendships helps
to lower the risk of suicide, as people with strong social
networks are less likely to give up on life.

Prognosis
The prognosis for a person who has attempted
suicide is generally favorable, although further
research needs to be done. A 1978 follow-up study of
515 people who had attempted suicide between 1937
and 1971 reported that 94% were either still alive or
had died of natural causes. This finding has been taken
to indicate that suicidal behavior is more likely to be a
passing response to an acute crisis than a reflection of
a permanent state of mind.

Prevention
One reason that suicide is such a tragedy is that
most self-inflicted deaths are potentially preventable.
Many suicidal people change their minds if they can be
helped through their immediate crisis; Dr. Richard
Seiden, a specialist in treating survivors of suicide
attempts, puts the high-risk period at 90 days after
the crisis. Some potential suicides change their minds
during the actual attempt; for example, a number of
people who survived jumping off the Golden Gate
GALE ENCYCLOPEDIA OF MEDICINE

Bridge told interviewers afterward that they regretted
their action even as they were falling and that they
were grateful they survived.
Brain research is another important aspect of suicide prevention. Since major depression is the single
most common psychiatric diagnosis in suicidal people,
earlier and more effective recognition of depression is
a necessary preventive measure. Known biological
markers for an increased risk of suicide can now be
correlated with personality profiles linked to suicidal
behavior under stress to help identify individuals at
risk. In addition, brain imaging studies using positron
emission tomography (PET) are presently in use to
detect abnormal patterns of serotonin uptake in specific regions of the brain. Genetic studies are also
yielding new information about inherited predispositions to suicide.
Another major preventive measure is education of
clinicians, media people, and the general public. In
2002 the CDC, the National Institutes of Health
(NIH), and several other government agencies joined
together to form the National Strategy for Suicide
Prevention, or NSSP. Education of the general public
includes a growing number of medical and government websites posting information about suicide, publications available for downloading, lists of books for
further reading, tips for identifying symptoms of
depressed and suicidal thinking, and advice about
helping friends or loved ones who may be at risk.
Many of these websites also have direct connections
to suicide hotlines.
The National Institute of Mental Health (NIMH)
recommends the following action steps for anyone
dealing with a suicidal person:


Make sure that someone is with them at all times; do
not leave them alone even for a short period of time.



Persuade them to call their family doctor or the
nearest hospital emergency room.



Call 911 yourself.



Keep the person away from firearms, drugs, or other
potential means of suicide.

Resources
BOOKS

Alvarez, A. The Savage God: A Study of Suicide. New York:
Random House, Inc., 1972. A now-classic study of
suicide written for general readers. The author includes
a historical overview of suicide along with accounts of
his own suicide attempt and the suicide of his friend, the
poet Sylvia Plath.
American Psychiatric Association.Diagnostic and Statistical
Manual of Mental Disorders, 4th edition, text revision.
3591

Suicide

suicide intended to reduce the risk of suicide by
contagion.

Suicide

KEY TERMS

Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Assisted suicide—A form of self-inflicted death in
which a person voluntarily brings about his or her
own death with the help of another, usually a physician, relative, or friend.
Cortisol—A hormone released by the cortex (outer
portion) of the adrenal gland when a person is
under stress. Cortisol levels are now considered a
biological marker of suicide risk.
Euthanasia—The act of putting a person or animal
to death painlessly or allowing them to die by withholding medical services, usually because of a
painful and incurable disease. Mercy killing is
another term for euthanasia.
Frontal cortex—The part of the human brain associated with aggressiveness and impulse control.
Abnormalities in the frontal cortex are associated
with an increased risk of suicide.
Psychodynamic—A type of explanation of human
behavior that regards it as the outcome of interactions between conscious and unconscious factors.
Serotonin—A chemical that occurs in the blood
and nervous tissue and functions to transmit signals
across the gaps between neurons in the central
nervous system. Abnormally low levels of serotonin
are associated with depression and an increased
risk of suicide.
Suicide gesture—Attempted suicide characterized
by a low-lethality method, low level of intent or
planning, and little physical damage. Pseudocide is
another term for a suicide gesture.

Washington, DC: American Psychiatric Association,
2000.
‘‘Depression.’’ In The Merck Manual of Geriatrics, edited
by Mark H. Beers, MD, and Robert Berkow, MD.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
‘‘Psychiatric Emergencies.’’ In The Merck Manual of
Diagnosis and Therapy, edited by Mark H. Beers, MD,
and Robert Berkow, MD. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
‘‘Suicidal Behavior.’’ In The Merck Manual of Diagnosis and
Therapy, edited by Mark H. Beers, MD, and Robert
Berkow, MD. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
‘‘Suicide in Children and Adolescents.’’ In The Merck
Manual of Diagnosis and Therapy, edited by
Mark H. Beers, MD, and Robert Berkow, MD.
3592

Friend, Tad ‘‘Letter from California: Jumpers.’’ New
Yorker, 10 November 2003. <http://newyorker.com/
printable/?fact/031013fa_fact>. A journalist’s account
of the Golden Gate Bridge in San Francisco, the world’s
leading location for suicide.
Fu, Q., A. C. Heath, K. K. Bucholz, et al. ‘‘A Twin Study of
Genetic and Environmental Influences on Suicidality in
Men.’’ Psychology in Medicine 32 (January 2002):
11-24.
Plunkett, A., B. O’Toole, H. Swanston, et al. ‘‘Suicide Risk
Following Child Sexual Abuse.’’ Ambulatory Pediatrics
1 (September-October 2001): 262-266.
Soreff, Stephen, MD. ‘‘Suicide.’’ eMedicine, 3 September
2004. <http://www.emedicine.com/med/
topic3004.htm>.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry.
3615 Wisconsin Avenue, NW, Washington, DC 200163007. (202) 966-7300. Fax: (202) 966-2891. <http://
www.aacap.org.>.
American Association of Suicidology. Suite 408, 4201
Connecticut Avenue, NW, Washington, DC 20008.
(202) 237-2280. Fax: (202) 237-2282. <http://
www.suicidology.org.>.
American Foundation for Suicide Prevention (AFSP). 120
Wall Street, 22nd Floor, New York, NY 10005. (888)
333-2377 or (212)
Centers for Disease Control and Prevention (CDC),
National Center for Injury Prevention and Control
(NCIPC). Mailstop K60, 4770 Buford Highway,
Atlanta, GA 30341-3724. (770) 488-4362. Fax: (770)
488-4349. <http://www.cdc.gov/ncipc.htm>.
National Institute of Mental Health (NIMH). 6001
Executive Boulevard, Room 8184, MSC 9663,
Bethesda, MD 20892-9663. (301) 443-4513 or (886) 615NIMH. <www.nimh.nih.gov.>.
OTHER

American Academy of Child and Adolescent Psychiatry
(AACAP). Teen Suicide. AACAP Facts for Families
#10. Washington, DC: AACAP, 2004.
Centers for Disease Control and Prevention, National
Center for Injury Prevention and Control. ‘‘Suicide
Contagion and the Reporting of Suicide:
Recommendations from a National Workshop.’’
Morbidity and Mortality Weekly Report 43 (22 April
1994): 9–18. <http://www.cdc.gov/mmwr/preview/
mmwrhtml/00031539.htm.>.
Centers for Disease Control and Prevention, National
Center for Injury Prevention and Control. Suicide: Fact
Sheet. <http://www.cdc.gov/ncipc/factsheets/
suifacts.htm.>.
National Institute of Mental Health (NIMH). In Harm’s
Way: Suicide in America. NIH Publication No. 03GALE ENCYCLOPEDIA OF MEDICINE

Rebecca Frey, PhD

Sulfacetamide see Antibiotics, ophthalmic
Sulfamethoxazole and trimethoprim see
Sulfonamides
Sulfinpyrazone see Gout drugs

Always take sulfonamides exactly as directed. To
make sure the infection clears up completely, take the
medicine for as long as it has been prescribed. Do not
stop taking the drug just because symptoms begin to
improve. Symptoms may return if the drug is stopped
too soon.
Sulfonamides work best when they are at constant
levels in the blood. To help keep levels constant, take
the medicine in doses spaced evenly through the day
and night. Do not miss any doses. For best results,
take the medicine with a full glass of water and drink
several more glasses of water every day. This will help
prevent some of the medicine’s side effects.

Sulfisoxazole see Sulfonamides
Precautions

Sulfonamides
Definition
Sulfonamides are medicines that prevent the
growth of bacteria in the body.

Purpose
Sulfonamides are used to treat many kinds of
infections caused by bacteria and certain other microorganisms. Physicians may prescribe these drugs to
treat urinary tract infections, ear infections, frequent
or long-lasting bronchitis, bacterial meningitis, certain
eye infections, Pneumocystis carinii pneumonia, traveler’s diarrhea, and a number of other kinds of infections. These drugs will not work for colds, flu, and
other infections caused by viruses.

Description
Sulfonamides, also called sulfa medicines, are
available only with a physician’s prescription. They
are sold in tablet and liquid forms. Some commonly
used sulfonamides are sulfisoxazole (Gantrisin) and
the combination drug sulfamethoxazole and trimethoprim (Bactrim, Cotrim).

Recommended dosage
The recommended dosage depends on the type of
sulfonamide, the strength of the medicine, and the
medical problem for which it is being taken. Check
with the physician who prescribed the drug or the
pharmacist who filled the prescription for the correct
dosage.
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms should begin to improve within a few
days of beginning to take this medicine. If they do not,
or if they get worse, check with the physician who
prescribed the medicine.
Although such side effects are rare, some people
have had severe and life-threatening reactions to sulfonamides. These include sudden, severe liver damage,
serious blood problems, breakdown of the outer layer
of the skin, and a condition called Stevens-Johnson
syndrome, in which people get blisters around the
mouth, eyes, or anus. Call a physician immediately if
any of these signs of a dangerous reaction occur:


skin rash or reddish or purplish spots on the skin



other skin problems, such as blistering or peeling



fever



sore throat



cough



shortness of breath



joint pain



pale skin



yellow skin or eyes

This medicine may cause dizziness. Anyone who
takes sulfonamides should not drive, use machines or
do anything else that might be dangerous until they
have found out how the drugs affect them.
Sulfonamides may cause blood problems that can
interfere with healing and lead to additional infections. Avoid injuries while taking this medicine. Be
especially careful not to injure the mouth when brushing or flossing the teeth or using a toothpick. Do not
have dental work done until the blood is back to
normal.
3593

Sulfonamides

4594. Bethesda, MD: NIMH, 2003. <http://
www.nimh.nih.gov/publicat/NIMHharmsway.pdf>.
National Suicide Hotline: (800) 273-TALK (1-800-2738255).

Sulfonamides

This medicine may increase sensitivity to sunlight.
Even brief exposure to sun can cause a severe sunburn
or a rash. While being treated with this medicine,
avoid being in direct sunlight, especially between 10
A.M. and 3 P.M.; wear a hat and tightly woven clothing that covers the arms and legs; use a sunscreen with
a skin protection factor (SPF) of at least 15; protect
the lips with a sun block lipstick; and do not use
tanning beds, tanning booths, or sunlamps.
Babies under 2 months should not be given sulfonamides unless their physician has ordered the
medicine.
Older people may be especially sensitive to the
effects of sulfonamides, increasing the chance of
unwanted side effects, such as severe skin problems
and blood problems. Patients who are taking water
pills (diuretics) at the same time as sulfonamides may
also be more likely to have these problems.

should make sure their physicians are aware of their
conditions:


anemia or other blood problems



kidney disease



liver disease



asthma or severe allergies



alcohol abuse



poor nutrition



abnormal intestinal absorption



porphyria



folic acid deficiency



deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD)

USE OF CERTAIN MEDICINES. Taking sulfonamides
with certain other drugs may affect the way the drugs
work or may increase the chance of side effects.

Special conditions
People with certain medical conditions or who are
taking certain other medicines can have problems if
they take sulfonamides. Before taking these drugs, be
sure to let the physician know about any of these
conditions:
ALLERGIES. Anyone who has had unusual reactions to sulfonamides, water pills (diuretics), diabetes
medicines, or glaucoma medicine in the past should let
his or her physician know before taking sulfonamides.
The physician should also be told about any allergies
to foods, dyes, preservatives, or other substances.

Side effects
The most common side effects are mild diarrhea,
nausea, vomiting, dizziness, headache, loss of appetite,
and tiredness. These problems usually go away as the
body adjusts to the drug and do not require medical
treatment.
More serious side effects are not common, but
may occur. If any of the following side effects occur,
check with a physician immediately:


itching or skin rash



reddish or purplish spots on the skin



other skin problems, such as redness, blistering,
peeling



severe, watery or bloody diarrhea



muscle or joint aches



fever



sore throat



cough



shortness of breath



unusual tiredness or weakness



unusual bleeding or bruising



pale skin



yellow eyes or skin



swallowing problems

PREGNANCY. In studies of laboratory animals,

some sulfonamides cause birth defects. The drugs’
effects on human fetuses have not been studied.
However, pregnant women are advised not to use
this medicine around the time of labor and delivery,
because it can cause side effects in the baby. Women
who are pregnant or who may become pregnant
should check with their physicians about the safety
of using sulfonamides during pregnancy.
BREASTFEEDING. Sulfonamides pass into breast

milk and may cause liver problems, anemia, and
other problems in nursing babies whose mothers take
the medicine. Because of those problems, women
should not breastfeed when they are under treatment
with this drug. Women who are breastfeeding and who
need to take this medicine should check with their
physicians to find out how long they need to stop
breastfeeding.
OTHER MEDICAL CONDITIONS. Before using sulfo-

namides, people with any of these medical problems
3594

Other rare side effects may occur. Anyone who
has unusual symptoms while taking sulfonamides
should get in touch with his or her physician.
GALE ENCYCLOPEDIA OF MEDICINE

Anemia—A lack of hemoglobin–the compound in
blood that carries oxygen from the lungs throughout the body and brings waste carbon dioxide from
the cells to the lungs, where it is released.
Bronchitis—Inflammation of the air passages of the
lungs.
Fetus—A developing baby inside the womb.
Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Meningitis—Inflammation of tissues that surround
the brain and spinal cord.
Pneumocystis carinii pneumonia—A lung infection that affects people with weakened immune
systems, such as people with AIDS or people taking
medicines that weaken the immune system.
Porphyria—A disorder in which porphyrins build
up in the blood and urine.
Porphyrin—A type of pigment found in living
things.
Urinary tract—The passage through which urine
flows from the kidneys out of the body.

Interactions
Sulfonamides may interact with a large number of
other medicines. When this happens, the effects of one
or both of the drugs may change or the risk of side
effects may be greater. Anyone who takes sulfonamides should let the physician know all other medicines he or she is taking. Among the drugs that may
interact with sulfonamides are:


acetaminophen (Tylenol)



medicine for overactive thyroid



male hormones (androgens)



female hormones (estrogens)



other medicines used to treat infections



birth control pills



medicines for diabetes such as glyburide (Micronase)



anticoagulants such as warfarin (Coumadin)



disulfiram (Antabuse), used to treat alcohol abuse



amantadine (Symmetrel), used to treat flu and also
Parkinson’s disease



water pills (diuretics) such as hydrochlorothiazide
(HCTZ, HydroDIURIL)

GALE ENCYCLOPEDIA OF MEDICINE



the anticancer drug methotrexate (Rheumatrex)



antiseizure medicines such as valproice acid
(Depakote, Depakene)

The list above does not include every drug that
may interact with sulfonamides. Be sure to check with
a physician or pharmacist before combining sulfonamides with any other prescription or nonprescription
(over-the-counter) medicine.
Nancy Ross-Flanigan

Sumatriptan see Antimigraine drugs

Sunburn
Definition
Inflammation of the skin caused by overexposure
to the sun.

Description
Sunburn is caused by exposure to the ultraviolet
(UV) rays of the sun. There are two types of ultraviolet
rays, UVA and UVB. UVA rays penetrate the skin
more deeply and can cause melanoma in susceptible
people. UVB rays, which don’t penetrate as deeply,
cause sunburn and wrinkling. Most UVB rays are
absorbed by sunscreens, but only about half the
UVA rays are absorbed.
Skin cancer from sun overexposure is a serious
health problem in the United States, affecting almost
a million Americans each year. One out of 87 will
develop malignant melanoma, the most serious type
of skin cancer, and 7,300 of them will die each year.
Fair-skinned people are most susceptible to sunburn, because their skin produces only small amounts
of the protective pigment called melanin. People trying
to get a tan too quickly in strong sunlight are also more
vulnerable to sunburn. While they have a lower risk,
even the darkest-skinned people can get skin cancer.
Repeated sun overexposure and burning can prematurely age the skin, causing yellowish, wrinkled
skin. Overexposure can increase the risk of skin cancer, especially a serious burn in childhood.

Causes and symptoms
The ultraviolet rays in sunlight destroy cells in the
outer layer of the skin, damaging tiny blood vessels
3595

Sunburn

KEY TERMS

Sunburn

KEY TERMS
Malignant melanoma—The most deadly of the
three types of skin cancer.
Sunscreen—Products which block the damaging
rays of the sun. Good sunscreens contain either
para-aminobenzoic acid (PABA) or benzophenone, or both. Sunscreen protection factors range
from 2–45.

This person has a second-degree sunburn on the back of the
neck. (Custom Medical Stock Photo. Reproduced by permission.)

underneath. When the skin is burned, the blood vessels
dilate and leak fluid. Cells stop making protein. Their
DNA is damaged by the ultraviolet rays. Repeated
DNA damage can lead to cancer.
When the sun burns the skin, it triggers immune
defenses which identify the burned skin as foreign. At
the same time, the sun transforms a substance on the
skin which interferes with this immune response.
While this substance keeps the immune system from
attacking a person’s own skin, it also means that any
malignant cells in the skin will be able to grow freely.
Sunburn causes skin to turn red and blister.
Several days later, the dead skin cells peel off. In severe
cases, the burn may occur with sunstroke (vomiting,
fever and collapse).

Diagnosis
Visual inspection and a history of exposure to the
sun.

Treatment
Aspirin can ease pain and inflammation. Tender
skin should be protected against the sun until it has
healed. In addition, apply:


calamine lotion



sunburn cream or spray



cool tap water compress



colloidal oatmeal (Aveeno) baths



dusting powder to reduce chafing

People who are severely sunburned should see a
doctor, who may prescribe corticosteroid cream to
speed healing.
3596

Alternative treatment
Over-the-counter preparations containing aloe
(Aloe barbadensis) are an effective treatment for sunburn, easing pain and inflammation while also relieving dryness of the skin. A variety of topical herbal
remedies applied as lotions, poltices, or compresses
may also help relieve the effects of sunburn.
Calendula (Calendula officinalis) is one of the most
frequently recommended to reduce inflammation.

Prognosis
Moderately burned skin should heal within a
week. While the skin will heal after a sunburn, the
risk of skin cancer increases with exposure and subsequent burns. Even one bad burn in childhood carries
an increased risk of skin cancer.

Prevention
Everyone from age six months on should use a
water-resistant sunscreen with a sun protective factor
(SPF) of at least 15. Apply at least an ounce 15–30
minutes before going outside. It should be reapplied
every two hours (more often after swimming). Babies
should be kept completely out of the sun for the first
six months of life, because their skin is thinner than
older children. Sunscreens have not been approved for
infants.
In addition, people should:


limit sun exposure to 15 minutes the first day, even if
the weather is hazy, slowly increasing exposure daily



reapply sunscreen every two hours (more often if
sweating or swimming)



reapply waterproof sunscreen after swimming more
than 80 minutes, after toweling off, or after perspiring heavily



avoid the sun between 10 A.M. and 3 P.M.
GALE ENCYCLOPEDIA OF MEDICINE

use waterproof sunscreen on legs and feet, since the
sun can burn even through water



wear an opaque shirt in water, because reflected rays
are intensified

If using a sunscreen under SPF 15, simply applying more of the same SPF won’t prolong allowed time
in the sun. Instead, patients should use a higher SPF in
order to lengthen exposure safely. A billed cap protects 70% of the face; a wide-brimmed hat is better.
People at very high risk for skin cancer can wear
clothing that blocks almost all UV rays, but most
people can simply wear white cotton summer-weight
clothing with a tight weave.
Resources
PERIODICALS

Tyler, Varro. ‘‘Aloe: Nature’s Skin Soother.’’ Prevention
Magazine April 1, 1998: 94-96.

Carol A. Turkington

Sunscreens

effects may take longer to show up. In particular,
UV-A may have a role in causing melanoma. Most
sunscreen products contain ingredients that provide
adequate protection only against UV-B rays. Even
those labeled as broad-spectrum sunscreens may
offer only partial protection against UV-A radiation.
Those containing the ingredient avobenzone give the
most protection against UV-A rays.
Some medical experts are concerned that sunscreens give people a false sense of security, allowing
them to stay in the sun longer than they should.
Although sunscreens protect the skin from burning,
they may not protect against other kinds of damage. A
number of studies suggest that people who use sunscreens may actually increase their risk of melanoma
because they spend too much time in the sun. This
does not mean that people should stop using sunscreens. It means that they should not rely on sunscreens
alone for protection. According to the American
Academy of Dermatology, sunscreens should be
one part of sun protection, along with wide-brimmed
hats and tightly-woven clothing that covers the arms
and legs.
Sunscreens are also recommended for patients
with rosacea or other skin disorders that are aggravated by exposure to sunlight.

Definition
Sunscreens are products applied to the skin to
protect against the harmful effects of the sun’s ultraviolet (UV) rays.

Purpose
Everyone needs a little sunshine. About 15 minutes of exposure a day helps the body make Vitamin
D, which is important for healthy bones and teeth. But
longer exposure may cause many problems, from
wrinkles to skin cancer. One particularly deadly form
of skin cancer, malignant melanoma, has been on the
rise in recent decades, as tanning has become more
popular. Over the same period, scientists have warned
that the thin layer of ozone that protects life on Earth
from the sun’s ultraviolet (UV) radiation is being
depleted. This allows more UV radiation to get
through, adding to the risk of overexposure.
Sunscreens help protect against the sun’s damaging effects. But just how much protection they provide is a matter of debate. The sun gives off two kinds
of ultraviolet radiation, called UV-A and UV-B. For
many years, experts thought that only UV-B was
harmful. However, recent research suggests that UVA may be just as dangerous as UV-B, although its
GALE ENCYCLOPEDIA OF MEDICINE

Description
Many brands of sunscreens are available, containing a variety of ingredients. The active ingredients
work by absorbing, reflecting, or scattering some or
all of the sun’s rays. Most sunscreen products contain
combinations of ingredients.
The U.S. Food and Drug Administration (FDA)
has required sunscreen products to carry a sun protection factor (SPF) rating on their labels since 1999. This
number tells the consumer how well the sunscreen
protects against burning. The higher the number, the
longer a person can stay in the sun without burning.
Sunscreens are usually grouped into two major
categories, namely chemical absorbers and physical
blockers. Chemical absorbers absorb high-intensity
UV rays while physical blockers reflect or scatter
them. Chemical absorber compounds include avobenzone, padimate O, octyl methoxycinnamate, octisalate, and octocrylene. Physical blocker compounds
include titanium dioxide and zinc oxide. The chief
drawback of the physical blockers is their tendency
to leave a white film on the skin, causing many people
to use less of the product than they should for full sun
protection.
3597

Sunscreens



Sunscreens

A plant-derived compound that shows promise as
a sunscreen is nobiletin, a flavonoid extracted from
Citrus depressa or flat orange, a small citrus fruit
native to Taiwan and Okinawa. Topical application
of nobiletin has been shown to be effective in preventing the swelling and reddening of the skin associated
with overexposure to sunlight.
Sunscreen products are sold as lotions, creams,
gels, oils, sprays, sticks, and lip balms, and can be
bought without a physician’s prescription.

Recommended dosage
One should be sure to read the instructions that
come with the product. Some need to be applied as
long as one or two hours before sun exposure. Others
should be applied 15–30 minutes before exposure, and
reapplied frequently during exposure.
People should apply sunscreen liberally to all
exposed parts of the skin, including the hands, feet,
nose, ears, neck, scalp (if the hair is thin or very short),
and eyelids. They should take care not to get sunscreen
in the eyes, as it can cause irritation. People should
also use a lip balm containing sunscreen to protect the
lips, and reapply sunscreen liberally every 1–2 hours—
more frequently when perspiring heavily or after
swimming.

Precautions
Sunscreen alone will not provide full protection
from the sun. When possible, one should wear a hat,
long pants, long-sleeved shirts or blouses, and sunglasses. Try to stay out of the sun between 10 A.M.
and 2 P.M. (11 A.M. to 3 P.M. Daylight Saving Time),
when the sun’s rays are strongest. The sun can damage
the skin even on cloudy days, so get in the habit of
using a sunscreen every day. Be especially careful at
high elevations or in areas with surfaces that reflect the
sun’s rays, such as sand, water, concrete, or snow.
Sunlamps, tanning beds, and tanning booths were
once thought to be safer than the sun, because they
give off mainly UV-A rays. However, UV-A rays are
now known to cause serious skin damage and may
increase the risk of melanoma. Heatlh experts advise
people not to use these tanning devices.
People with fair skin, blond, red or light-brown
hair, and blue or light-colored eyes are at greatest risk
for developing skin cancer. So are people with many
large skin moles. These people should avoid exposure
to the sun as much as possible. However, even darkskinned people, including African Americans and
3598

Hispanic Americans may suffer skin damage from
the sun and should be careful about exposure.
Other groups of people who should minimize
sun exposure are those who have had organ transplants or recent plastic surgery. Patients who have
received organ transplants have a greatly increased
risk of developing skin cancer, and the facial skin
of people who have had face lifts or similar plastic
surgery procedures sunburns more easily than
intact skin.
Sunscreens should not be used on infants under 6
months of age because of the risk of side effects.
Instead, children this young should be kept out of
the sun. Children over 6 months should be protected
with clothing and sunscreens of at least SPF 15, preferably lotions. Sunscreens containing alcohol should
not be used on children because they may irritate
the skin.
Older people who stay out of the sun and use
sunscreens may not produce enough vitamin D in
their bodies. They may need to increase the vitamin
D in their diets by including foods such as fortified
milk and salmon. A health care professional can help
decide if this precaution is necessary.
Anyone who has had unusual reactions to any
sunscreen ingredients in the past should check with a
physician or pharmacist before using a sunscreen. The
physician or pharmacist should also be told about any
allergies to foods, dyes, preservatives, or other substances, especially the following:


artificial sweeteners



such anesthetics as benzocaine, procaine, or
tetracaine



diabetes medicine taken by mouth



hair dyes



sulfa medicines



water pills



cinnamon flavoring

People with skin conditions or diseases should
check with their physicians before using a sunscreen.
This is especially true of people with conditions that
get worse with exposure to light.

Side effects
The most common side effects are drying or tightening of the skin. This problem does not need medical
attention unless it does not improve.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Hair follicle—A tiny pit in the skin from which hair
grows.
Melanoma—A rapidly spreading and deadly form
of cancer that usually occurs on the skin.
Ozone—A gas found in the atmosphere. A layer of
ozone about 15 mi (24 km) above Earth’s surface
helps protect living things from the damaging
effects of the sun’s ultraviolet rays.
Pus—Thick, whitish or yellowish fluid that forms in
infected tissue.
Rosacea—A chronic skin disease characterized by
persistent redness of the skin and periodic outbreaks of pustules, usually affecting the middle
third of the face.
Ultraviolet rays—Invisible light rays with a wavelength shorter than that of visible light but longer
than that of x rays.

Other side effects are rare, but possible. If any of
the following symptoms occur, check with a physician
as soon as possible:


acne



burning, itching, or stinging of the skin



redness or swelling of the skin



rash, with or without blisters that ooze and become
crusted



pain in hairy parts of body



pus in hair follicles

Interactions
Anyone who is using a prescription or nonprescription (over-the-counter) drug that is applied to
the skin should check with a physician before using a
sunscreen.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Pigmentation Disorders.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Reactions to Sunlight.’’ In The Merck Manual of
GALE ENCYCLOPEDIA OF MEDICINE

Levy, Stanley B., MD. ‘‘Sunscreens and Photoprotection.’’
eMedicine November 25, 2002. <http://www.emedicine.com/derm/topic510.htm>.
Mahe, E., E. Morelon, J. Fermanian, et al. ‘‘RenalTransplant Recipients and Sun Protection.’’
Transplantation 78 (September 15, 2004): 741–744.
Murphy, G. ‘‘Ultraviolet Light and Rosacea.’’ Cutis 74,
Supplement 3 (September 2004): 13–16, 32–34.
Tanaka, S., T. Sato, N. Akimoto, et al. ‘‘Prevention of UVBInduced Photoinflammation and Photoaging by a
Polymethoxy Flavonoid, Nobiletin, in Human
Keratinocytes in Vivo and in Vitro.’’ Biochemical
Pharmacology 68 (August 1, 2004): 433–439.
ORGANIZATIONS

American Academy of Dermatology (AAD). P. O. Box
4014, Schaumburg, IL 60168-4014. (847) 330-0230.<
http://www.aad.org>.
American Society of Plastic Surgeons (ASPS). 444 East
Algonquin Road, Arlington Heights, IL 60005. (847)
228-9900. <htpp://www.plasticsurgery.org>.
National Institutes of Health. National Cancer Institute.
9000 Rockville Pike, Bethesda, MD 20982. Cancer
Information Service: (800) 4-CANCER. <http://
cancernet.nci.nih.gov>.
United States Food and Drug Administration (FDA). 5600
Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. <http://www.fda.gov>.

Nancy Ross-Flanigan
Rebecca J. Frey, PhD

Sunstroke see Heat disorders
Superficial phlebitis see Thrombophlebitis

Superior vena cava syndrome
Definition
The superior vena cava is the major vein in the
chest that carries blood from the upper part of the
body in to the heart. A restriction of the blood flow
(occlusion) through this vein can cause superior vena
cava syndrome (SVCS).

Description
Superior vena cava syndrome is a partial occlusion of the superior vena cava. This leads to a lower
than normal blood flow through this major vein.
3599

Superior vena cava syndrome

KEY TERMS

Superior vena cava syndrome

SVCS is also called superior mediastinal syndrome
and/or superior vena cava obstruction.

Causes and symptoms
More than 95% of all cases of SVCS are associated with cancers involving the upper chest. The
cancers most commonly associated with SVCS are
advanced lung cancers, which account for nearly
80% of all cases of SVCS, and lymphoma. Cancers
that have spread (metastasized) to the chest, such as
metastatic breast cancer to the chest and metastatic
testicular cancer to the chest have also been shown to
cause SVCS.
Other causes of SVCS include: the formation of a
blood clot in the superior vena cava, enlargement of
the thyroid gland, tuberculosis, and sarcoidosis.
The symptoms of SVCS include:


change in voice



confusion



cough



enlargement of the veins in the upper body, particularly those in the arms



headache



light-headedness



shortness of breath



swelling of the arms



swelling of the face



trouble swallowing

Diagnosis
SVCS should be considered in any cancer patient
with swelling of the face and arms. This diagnosis can
be confirmed by x ray, computerized tomography
(CT) scan, or medical resonance imaging (MRI) of
the chest that reveals a partial occlusion of the superior vena cava.

Treatment
Treatment of SVCS depends on the underlying
cancer that is causing it. This treatment may include
radiation, chemotherapy, or a combination of both. In
some cases, surgical procedures may be performed to
open (dilate) the vessel. These procedures are generally
performed by a trained radiologist or vascular
surgeon.
3600

KEY TERMS
Metastasis—The spread of a cancer from one part of
the body (where the cancer originated) to another
part of the body.
Sarcoidosis—A disease of unknown origin in which
there is chronic (recurrent) swelling in the lymph
nodes and other tissues.
Superior vena cava—The major vein that carries
blood from the upper body to the heart.
Thymoma—A tumor that originates in the thymus, a
small gland just in front of the heart that produces
hormones necessary for the development of certain
components of the immune system.

Alternative treatment
Since treatment of SVCS is aimed at treating the
underlying disorder that is causing SVCS, alternative
treatments must also focus on treating these underlying causes. Alternative treatments for cancer
include acupuncture, aromatherapy, herbal remedies,
hydrotherapy, hypnosis, and massage, among many
others.

Prognosis
The prognosis depends on the underlying cause of
SVCS. In cases of SVCS caused by lung cancers, the
prognosis is generally rather poor since SVCS does not
generally occur until the later stages of these diseases.

Prevention
SVCS may be prevented by early medical intervention to halt and/or reverse the cancer which, in a
later stage, would have lead to SVCS.
Resources
PERIODICALS

Haapoja, I.S., and C. Blendowski. ‘‘Superior Vena Cava
Syndrome.’’ Seminars in Oncology Nursing 15 (August
1999): 183-9.
Hemann, Rhonda. ‘‘Superior Vena Cava Syndrome.’’
Clinical Excellence for Nurse Practitioners 5 (March
2001): 85-7.
ORGANIZATIONS

Alliance for Lung Cancer Advocacy, Support and
Education. P.O. Box 849 Vancouver, WA 98666. (800)
298-2436. <http://www.alcase.org/>.

GALE ENCYCLOPEDIA OF MEDICINE

Beeson, Michael S. eMedicine - Superior Vena Cava
Syndrome. May 12, 2001. <http://www.emedicine.com/emerg/topic561.htm>.

Paul A. Johnson, Ed.M.

Supportive cancer therapy see Cancer
therapy, supportive

Surfactant
Definition
Surfactant is a complex naturally occurring substance made of six lipids (fats) and four proteins that is
produced in the lungs. It can also be manufactured
synthetically.

Purpose
Surfactant reduces the surface tension of fluid in
the lungs and helps make the small air sacs in the lungs
(alveoli) more stable. This keeps them from collapsing
when an individual exhales. In preparation for breathing air, fetuses begin making surfactant while still in
the womb. Babies that are born very prematurely
often lack adequate surfactant and must receive surfactant replacement therapy immediately after birth in
order to breathe.

Precautions
Babies are considered premature if they are born
before 37 weeks gestation. Fetuses begin to produce
surfactant between weeks 24 and 28. By about 35
weeks, most babies have enough naturally produced
surfactant to keep the alveoli from collapsing. Babies
born before 35 weeks, especially those born very prematurely (before 30 weeks), are likely to need surfactant replacement therapy. Over half the babies born
before 28 weeks gestation need this treatment, while
about one-third born between 32 and 36 weeks need
supplemental surfactant. Some very premature infants
may also need to be placed on a mechanical ventilator.

Description
The lungs consist of spongy tissue filled with air
spaces called alveoli. In the alveoli, oxygen is taken up
by the blood and carbon dioxide, a waste product of
cellular metabolism, is released and exhaled. For
GALE ENCYCLOPEDIA OF MEDICINE

efficient oxygen-carbon dioxide exchange to occur,
the surface area of the alveoli must be as large as
possible. Under normal conditions, when a person
exhales, the alveoli would collapse into each other
and form larger air sacs with less surface area.
Surfactant prevents this collapse by reducing the surface tension of the fluids that line the lungs and helping
to equalize the pressures between large and small air
spaces.
Surface tension is a measure of the attraction
molecules of a fluid have for each other. The attractive
force pulls fluids into a shape with the smallest surface
area. This is why a drop of water on a flat surface is
rounded rather than flat. If the surface tension is
lowered, the attraction among molecules of the fluid
is decreased and the surface area of the fluid increases.
For example, if a drop of detergent is added to a drop
of water, the detergent reduces the surface tension and
the drop of water flattens out.
In the lungs, surfactant reduces the surface tension and helps to maximize the surface area available
for gas exchange. Without adequate surfactant, a baby
works much harder to breathe, becomes exhausted,
and does not get enough oxygen. Babies that do not
have enough surfactant to breathe normally at birth
are said to have infant respiratory distress syndrome
(RDS) or hyaline membrane disease (HMD).
Babies with RDS are given replacement surfactant as soon as possible within the first six hours after
birth. Manufactured surfactant is a white powder that
is mixed with sterile water. It is given through a breathing tube (endotracheal tube) that is inserted in the
baby’s lungs. Multiple doses are usually required.
Surfactant replacement therapy continues until
the baby’s lungs have matured enough to make surfactant on their own. Some very premature babies are
also put on mechanical respirators to help them
breathe. Surfactant replacement therapy has reduced
deaths due to respiratory distress by 50% since the
early 1990s. This therapy is expensive, but it is normally covered by insurance.

Preparation
The administration of surfactant is often a neonatal emergency. The only way to prevent the need for
surfactant replacement therapy is to prevent a premature birth. Mothers who are at known high risk to
deliver prematurely are given drugs called corticosteroids toward the end of the pregnancy that stimulate the
lungs of the fetus to mature and begin producing
surfactant sooner. This helps reduce the need for
3601

Surfactant

OTHER

Swallowing disorders

KEY TERMS
Alveolus (plural alveoli)—The terminal air sacs of
the lungs where gas exchange occurs.
Hyaline membrane —A thin layer of cells that line
the lung.
Surface tension—The attraction of molecules in a
fluid for each other.

surfactant replacement therapy. Although babies of
all races may be born prematurely, prematurity is
more common if the mother is diabetic, is carrying
multiple fetuses, or has delivered a previous premature
baby. The decision to use surfactant replacement therapy is based on the condition of the baby, its blood
oxygen level, and degree of respiratory distress.

Aftercare
Babies receiving surfactant therapy are normally
cared for by a neonatologist, a pediatrician that specializes in newborn care. Premature newborns often
have other health problems in addition to RDS.
Aftercare varies depending on their other health risks.

Risks
Delivery of surfactant requires inserting a breathing tube into the baby’s lungs. Complications of this
therapy include air leaking into the area between the
chest wall and the lungs and air leaking into the sac
around the heart. Some infants also develop chronic
lung disease.

Normal results
Normally surfactant replacement therapy keeps
the infant alive until the lungs start producing their
own surfactant.

Abnormal results
Surfactant replacement therapy is very effective if
begun within six hours after birth. When it fails, death
may result.

2004 [cited 16 February 2005]. <http://www.thedoctorslounge.net/pedlounge/articles/surfactant>.
Hyaline Membrane Disease/Respiratory Distress Syndrome.
Lucile Packard Children’s Hospital at Stanford. 20012005 [cited 16 February 2005]. <http://www.lpch.org/
DiseaseHealthInfo/HealthLibrary/hrnewborn/
hmd.html>.
Pramanik, Arun. Respiratory Distress Syndrome, 2 July 2002
[cited 16 February 2005]. <http://www.emedicine.com/
ped/topic1993.htm>.
Surfactant. Johns Hopkins School of Medicine. 1995 [cited
16 February 2005]. <http://oac.med.jhmi.edu/
res_phys/Encyclopedia/Surfactant/
Surfactant.HTMLgt;

Tish Davidson, A.M.

Surgical debridement see Debridement

Swallowing disorders
Definition
Swallowing disorders include a number of diseases and conditions that cause difficulty in passing
food or liquid from the mouth to the stomach.

Description
Although normally swallowing is automatic, it is a
complex process involving several phases and 29 muscles. Saliva helps soften food as it is chewed. The
tongue helps move food to the back of the mouth,
triggering a swallowing reflex that passes food
through the pharynx. The epiglottis helps keep food
from mistakenly going down the windpipe and into
the esophagus, the canal that carries food to the stomach. Swallowing disorders can occur at any phase in
the swallowing process. The medical term for difficult
swallowing is dysphagia.
Each year, about 10 million people in the United
States require medical evaluation for swallowing problems. Some experts say that about 10% of Americans
develop symptoms of swallowing disorders in adulthood. Elderly people are the most likely to have problems with swallowing.

Causes and symptoms
Resources
OTHER

Doctors Lounge, The. ‘‘Chronically Ventilated Premature
Infants Need Continued Surfactant,’’ 15 November

3602

Swallowing disorders often result from other conditions and diseases. For example, Parkinson’s disease, cerebral palsy, stroke, head injury, and other
central nervous system conditions can damage the
GALE ENCYCLOPEDIA OF MEDICINE

Some cancers can lead to swallowing disorders.
Esophageal cancer can cause narrowing and eventual
blockage of the esophagus. Surgery and radiation therapy for head and neck cancer can restrict or weaken
tongue motion, paralyze vocal cords, or cause muscle
damage that affects swallowing. An inflamed esophagus, often resulting from gastroesophageal reflux disease (GERD), can cause painful or difficult
swallowing. Infections of the esophagus also can
inflame it and cause it to narrow. Swallowing difficulty may result from aging, though researchers are
not certain why.
The most common symptoms people report are
choking and the feeling that food feels stuck in the
throat. Other symptoms include needing to swallow
many times to clear food from the mouth and throat, a
gurgly, wet sound to the voice after swallowing, having to clear the throat after eating, coughing, pain
while swallowing, bringing food back up (regurgitation), food or acid backing up into the throat, unexpected weight loss, and not being able to swallow at
all. Children also may gag during meals and may have
excessive drooling or leaking of food or liquid from
their mouths during meals. They may have difficulty
breathing when eating or drinking, spit up frequently
and lag behind in weight gain. They also may have
recurring pneumonia or respiratory infections.

Diagnosis
A physician should perform a full head and neck
examination based on the patient’s symptoms.
Speech-language pathologists may aid in the diagnosis. Physicians also might order a swallowing test to
study how the patient swallows. The patient will be
asked to drink a liquid with a contrast agent called
barium that will show up on x rays of the throat and
upper chest. The exam might be imaged with a technique called video fluoroscopy, which will take motion
camera images in addition to still images. For this
exam, the patient may be asked to swallow liquid,
paste, and solids. A speech pathologist may work
with the radiologist to perform this exam.
If the physician thinks the problem originates in
the lower esophagus or has concerns about an
abnormality in the esophagus, an endoscopy may be
ordered. This test involves passing a thin, flexible
instrument called an endoscope down the throat. The
lighted endoscope helps the physician view the esophagus. Other tests may be used, including ultrasound.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cleft palate—An opening or hole in the roof of the
mouth that occurs at birth when the roof fails to
fully develop in the infant.
Epiglottis—A thin layer of cartilage behind the tongue that helps block food from entering the
windpipe.
Pharynx—The muscular cavity that leads from the
mouth and nasal passages to the larynx and
esophagus.

Treatment
Treatment will depend on the cause of the swallowing problem. Special exercises may help strengthen
the muscles used for chewing and swallowing.
Problems originating in the mouth may be treated
with artificial saliva, improved hydration or better
dental care. Esophageal problems will be treated
depending on the cause. Patients with GERD will
receive medications and instructions on how to better
manage the disease. Esophageal cancer is a life-threatening disease that will involve coordinating care with
an oncologist. Many patients will receive help with
their disorders from speech pathologists. Special
liquid diets may be ordered for patients who continue
to have trouble chewing or swallowing. In severe cases,
the patient may need a feeding tube that bypasses the
part of the swallowing system that does not work.

Alternative treatment
Some herbs that may help improve swallowing
include oil of peppermint and licorice. Valerian may
be used as a tea. Homeopathic physicians may suggest
some remedies aimed at improving bloating, indigestion, or cough. Alternative care should be sought from
licensed practitioners and coordinated with physician
care.

Prognosis
In many cases, these disorders can be corrected. If
not treated, swallowing disorders can lead to serious
complications, including dehydration and malnutrition. There also is a risk of food entering the airway
(aspiration) as a person attempts to swallow, which
can lead to aspiration pneumonia as the food particles
enter the lungs.
3603

Swallowing disorders

muscles and nerves involved in swallowing. Some people are born with abnormalities in the swallowing
structures, such as infants with cleft palate.

Sydenham’s chorea

Prevention
Many causes of swallowing disorders cannot be
prevented. Slowly and fully chewing food helps.
People with GERD should manage it to lower the
risk of developing swallowing difficulties.
Resources
PERIODICALS

‘‘Disorders of Swallowing.’’ Harvard Men’s Health Watch
(Sept. 2003).
‘‘The Evaluation and Management of Swallowing Disorders
in the Elderly.’’ Geriatric Times (Nov. 1, 2003): 17.
ORGANIZATIONS

American Academy of Otolaryngology-Head and Neck
Surgery. One Prince St., Alexandria, VA 22314-3357.
703-836-4444. http://www.entnet.org.
American Speech-Language Association (ASHA). 10801
Rockville Pike, Rockville, MD 20852. 800-638-8255.
http://www.asha.org.
National Institute of Dental and Craniofacial Research
(NIDCR). 45 Center Dr., Rm 4AS19 MSC 6400,
Bethesda, MD 20892-6400. 301-496-4261. http://
www.nidr.nih.gov.
OTHER

Dysphagia. Web page. National Institute on Deafness and
Other Communication Disorders, 2005. http://
www.nidcd.nih.gov/health/voice/dysph.asp.
NINDS Swallowing Disorders Information Page.Web page.
National Institute of Neurological Disorders and
Stroke, 2005. http://www.ninds.nih.gov/disorders/
swallowing_disorders/swallowing_disorders.htm.

Teresa G. Odle

Swan-Ganz catheterization see Pulmonary
artery catheterization
Sweating, excessive see Hyperhidrosis
Swimmer’s ear see Otitis externa
Swimming pool conjunctivitis see Inclusion
conjunctivitis
Swollen glands see Lymphadenitis

Sydenham’s chorea
Definition
Sydenham’s chorea is an acute but self-limited
movement disorder that occurs most commonly in
children between the ages of 5 and 15, and
3604

occasionally in pregnant women. It is closely associated with rheumatic fever following a throat infection. The disorder is named for Thomas Sydenham
(1624–1689), an English doctor who first described it
in 1686. Other names for Sydenham’s chorea include
simple chorea, chorea minor, acute chorea, rheumatic
chorea, juvenile chorea, and St. Vitus’ dance. The
English word ‘‘chorea’’ itself comes from the Greek
word choreia, which means ‘‘dance.’’ The disorder
takes its name from the rapid involuntary jerking or
twitching movements of the patient’s face, limbs, and
upper body.

Description
Sydenham’s chorea is a disorder that occurs in
children and is associated with rheumatic fever.
Rheumatic fever is an acute infectious disease caused
by certain types of streptococci bacteria. It usually
starts with strep throat or tonsillitis. These types of
streptococci are able to cause disease throughout the
body. The most serious damage caused by rheumatic
fever is to the valves in the heart. At one time, rheumatic fever was the most common cause of damaged
heart valves, and it still is in most developing countries
around the world. Rheumatic fever and rheumatic
heart disease are still present in the industrialized
countries, but the incidence has dropped substantially.
Both acute rheumatic fever and Sydenham’s
chorea are relatively uncommon disorders in the
United States as of 2004. According to the Centers
for Disease Control and Prevention (CDC), only
1%–3% of people with streptococcal throat infections
develop acute rheumatic fever (ARF); thus the incidence of ARF in the United States is thought to be
about 0.5 per 100,000 patients between 5 and 17 years
of age.
With regard to age, the incidence of Sydenham’s
chorea is higher in childhood and adolescence than in
adult life. It occurs more frequently in females than in
males; the gender ratio is thought to be about 2 F: 1 M.
Since the peak incidence of rheumatic fever in North
America occurs in late winter and spring, Sydenham’s
chorea is more likely to occur in the summer and early
fall. There is no evidence as of 2004 that the disorder
selectively affects specific racial or ethnic groups.
Rheumatic fever may appear in several different
forms. Sydenham’s chorea is one of five major criteria
for the diagnosis of rheumatic fever. There are also
four minor criteria and two types of laboratory tests
associated with the disease. The ‘‘Jones criteria’’
define the diagnosis. They require laboratory evidence
of a streptococcal infection plus two or more of the
GALE ENCYCLOPEDIA OF MEDICINE

About 20% of patients diagnosed with
Sydenham’s chorea experience a recurrence of the disorder, usually within two years of the first episode.
Most women who develop Sydenham’s during pregnancy have a history of acute rheumatic fever in childhood or of using birth control pills containing
estrogen.

Causes and symptoms
Sydenham’s is caused by certain types of streptococci called Group A beta-hemolytic streptococci or
GAS bacteria. In general, streptococci are sphericalshaped anaerobic bacteria that occur in pairs or
chains. GAS bacteria belong to a subcategory known
as pyogenic streptococci, which means that the infections they cause produce pus. These particular germs
seem to be able to create an immune response that
attacks the body’s own tissues along with the germs.
Those tissues are joints, heart valves, skin, and brain.
The initial throat infection that leads to
Sydenham’s chorea is typically followed by a symptom-free period of 1–5 weeks. The patient then develops an acute case of rheumatic fever (ARF), an
inflammatory disease that affects multiple organ systems and tissues of the body. In most patients, ARF is
characterized by fever, arthritis in one or more joints,
and carditis, or inflammation of the heart. In about
20% of patients, however, Sydenham’s chorea is the
only indication of ARF. Sydenham’s is considered a
delayed complication of rheumatic fever; it may begin
as late as 12 months after the initial sore throat, and it
may start only after the patient’s temperature and
other physical signs have returned to normal. The
average time interval between the pharyngitis and the
first symptoms of Sydenham’s, however, is eight or
nine weeks.
It is difficult to describe a ‘‘typical’’ case of
Sydenham’s chorea because the symptoms vary in
speed of onset as well as severity. Most patients have
an acute onset of the disorder, but in others, the onset
is insidious, which means that the symptoms develop
slowly and gradually. In some cases, the child’s physical symptoms are present for four to five weeks before
they become severe enough for the parents to consult a
doctor. In other cases, emotional or psychiatric
GALE ENCYCLOPEDIA OF MEDICINE

symptoms precede the clumsiness and involuntary
muscular movements that characterize the disorder.
The psychiatric symptoms that may develop in
patients with Sydenham’s chorea are one reason why
it is sometimes categorized as a PANDAS disorder.
PANDAS stands for Pediatric Autoimmune
Neuropsychiatric
Disorders
Associated
with
Streptococcal Infections.
Behavioral or emotional disturbances that have
been observed with Sydenham’s include:


frequent mood changes



episodes of uncontrollable crying



behavioral regression; that is, acting like much
younger children



mental confusion



general irritability



difficulty concentrating



impulsive behavior

Some researchers think that children who have
had Sydenham’s are at increased risk of developing
obsessive-compulsive disorder (OCD). OCD is characterized by obsessions, which are unwanted recurrent
thoughts, images, or impulses, and by compulsions,
which are repetitive rituals, mental acts, or behaviors.
Obsessions in children often take the form of fears of
intruders or harm coming to a family member.
Compulsions may include such acts as counting
silently, washing the hands over and over, insisting
on keeping items in a specific order, checking repeatedly to make sure a door is locked, and similar
behaviors.

Diagnosis
Because rheumatic fever is such a damaging disease, a complete evaluation should be done whenever
it is suspected. This includes cultures for streptococci,
blood tests, and usually an electrocardiogram (heartbeat mapping to detect abnormalities).
The diagnosis of Sydenham’s is also based on the
doctor’s observation of the patient’s involuntary
movements. Unlike tics, the movements associated
with chorea are not repetitive; and unlike the behavior
of hyperactive children, the movements are not intentional. The recent onset of the movements rules out a
diagnosis of cerebral palsy. If the doctor suspects
Sydenham’s, he or she may ask the patient to stick
out the tongue and keep it in that position, or to
squeeze the doctor’s hand. Many patients with
Sydenham’s cannot hold their mouth open and keep
3605

Sydenham’s chorea

criteria. The laboratory evidence may be identification
of streptococci from a sore throat or antibodies to
streptococcus in the blood. The most common criteria
are arthritis and heart disease, occurring in half to
three-quarters of the patients. Sydenham’s chorea,
characteristic nodules under the skin, and a specific
type of skin rash occur only 10% of the time.

Sydenham’s chorea

the tongue out for more than a second or two. Another
characteristic of Sydenham’s is an inability to grip
with a steady pressure; when the patient squeezes the
doctor’s hand, the strength of the grip will increase
and decrease in an erratic fashion. This characteristic
is sometimes called the ‘‘milking sign.’’

Treatment
Suspected streptococcal infections must be treated. All the other manifestations of rheumatic fever,
including Sydenham’s chorea and excluding heart
valve damage, remit with the acute disease and do
not require treatment. Sydenham’s chorea generally
lasts for several months.
Most patients with Sydenham’s chorea recover
after a period of bed rest and temporary limitation of
normal activities. In most cases the symptoms disappear gradually rather than stopping abruptly.
Most doctors recommend ongoing treatment with
penicillin to prevent a recurrence of rheumatic fever or
Sydenham’s chorea, although there is some disagreement as to whether this treatment should continue for
5 years after an acute attack or for the rest of the
patient’s life. The penicillin may be given orally or by
injection. Patients who cannot take penicillin may be
given erythromycin or sulfadiazine.

Prognosis
Syndenham’s chorea usually clears up without
complications when the rheumatic fever is treated.
The heart valve damage associated with rheumatic
fever may lead to heart trouble and require a surgical
valve repair or replacement.
In most cases of Sydenham’s, the patient recovers
completely, although a recurrence is possible. In a very
few cases—about 1.5% of patients diagnosed with
Sydenham’s— there may be increasing muscle stiffness and loss of muscle tone resulting in disability.
This condition is occasionally referred to as paralytic
chorea

Prevention
All cases of strep throat in children should be
treated with a full 10 days of antibiotics (penicillin or
erythromycin). Treatment may best be delayed a day
or two to allow the body to build up its own antibodies. In addition, for those who have had an episode of
rheumatic fever or have damaged heart valves from
any other cause, prophylactic antibiotics should be
continued to prevent recurrence.
3606

KEY TERMS
Arthralgia—Joint pain.
Chorea—A term that is used to refer to rapid, jerky,
involuntary movements of the limbs or face that
characterize several different disorders of the nervous system, including chorea of pregnancy and
Huntington’s chorea as well as Sydenham’s
chorea.
Electrocardiogram—Mapping the electrical activity of the heart.
Insidious—Developing in a stealthy or gradual
manner. Sydenham’s chorea may have an insidious
onset.
PANDAS disorders—A group of childhood disorders associated with such streptococcal infections
as scarlet fever and ‘‘strep throat.’’ The acronym
stands for Pediatric Autoimmune Neuropsychiatric
Disorders
Associated
with
Streptococcal
Infections. Sydenham’s chorea is considered a
PANDAS disorder.
Pharyngitis—Inflammation of the throat, accompanied by dryness and pain. Pharyngitis caused by a
streptococcal infection is the usual trigger of
Sydenham’s chorea.
Rheumatic fever—Chiefly childhood disease
marked by fever, inflammation, joint pain, and
Syndenham’s chorea. It is often recurrent and can
lead to heart valve damage.
St. Vitus’ dance—Another name for Sydenham’s
chorea. St. Vitus was a fourth-century martyr who
became the patron saint of dancers and actors during the Middle Ages. He was also invoked for protection against nervous disorders, epilepsy, and the
disease that bears his name.
Streptococcus (plural, streptococci)—A genus of
spherical-shaped anaerobic bacteria occurring in
pairs or chains. Sydenham’s chorea is considered a complication of a streptococcal throat
infection.
Tonsillitis—Inflammation of the tonsils, which are
in the back of the throat.

It is possible to eradicate dangerous GAS bacteria from a community by culturing everyone’s
throat and treating everyone who tests positive.
This is worth doing wherever a case of rheumatic
fever appears, but it is expensive and requires many
resources.
GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

<http://www.ninds.nih.gov/health_and_medical/disorders/sydenham.htm>.

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Sydenham’s Chorea (Chorea Minor; Rheumatic
Fever; St. Vitus’ Dance).’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.

J. Ricker Polsdorfer, MD
Rebecca J. Frey, PhD

PERIODICALS

Bhidayasiri, R., and D. D. Truong. ‘‘Chorea and Related
Disorders.’’ Postgraduate Medical Journal 80
(September 2004): 527–534.
Bonthius, D. J., and B. Karacay. ‘‘Sydenham’s Chorea: Not
Gone and Not Forgotten.’’ Seminars in Pediatric
Neurology 10 (March 2003): 11–19.
Dale, R. C., I. Heyman, R. A. Surtees, et al. ‘‘Dyskinesias
and Associated Psychiatric Disorders following
Streptococcal Infections.’’ Archives of Disease in
Childhood 89 (July 2004): 604–610.
Herrera, Maria Alejandra, MD, and Nestor GalvezJiminez, MD. ‘‘Chorea in Adults.’’ eMedicine
February 1, 2002. <http://www.emedicine.com/
neuro/topic62.htm>.
Kim, S. W., J. E. Grant, S. I. Kim, et al. ‘‘A Possible
Association of Recurrent Streptococcal Infections and
Acute Onset of Obsessive-Compulsive Disorder.’’
Journal of Neuropsychiatry and Clinical Neurosciences
16 (Summer 2004): 252–260.
Korn-Lubetzki, I., A. Brand, and I. Steiner. ‘‘Recurrence of
Sydenham Chorea: Implications for Pathogenesis.’’
Archives of Neurology 61 (August 2004): 1261–1264.
Snider, L. A., and S. E. Swedo. ‘‘Post-Streptococcal
Autoimmune Disorders of the Central Nervous
System.’’ Current Opinion in Neurology 16 (June 2003):
359–365.
ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry
(AACAP). 3615 Wisconsin Avenue, NW, Washington,
DC 20016-3007. (202) 966-7300. Fax: (202) 966-2891.
<http://www.aacap.org>.
American Academy of Family Physicians (AAFP). 11400
Tomahawk Creek Parkway, Leawood, KS 66211-2672.
(800) 274-2237 or (913) 906-6000. *lt;http://
www.aafp.org>.
National Institute of Neurological Disorders and Stroke
(NINDS). NIH Neurological Institute, P. O. Box 5801,
Bethesda, MD 20824. (800) 352-9424 or (301) 496-5751.
<http://www.ninds.nih.gov>.
OTHER

American Academy of Child and Adolescent Psychiatry
(AACAP). AACAP Facts for Families, No. 60.
Obsessive-Compulsive Disorder in Children and
Adolescents. <http://www.aacap.org/publications/
factsfam/ocd.htm>.
National Institute of Neurological Disorders and Stroke
(NINDS). NINDS Sydenham Chorea Information Page.
GALE ENCYCLOPEDIA OF MEDICINE

Sympathectomy
Definition
Sympathectomy is a surgical procedure that
destroys nerves in the sympathetic nervous system.
The procedure is done to increase blood flow and
decrease long-term pain in certain diseases that cause
narrowed blood vessels. It can also be used to decrease
excessive sweating. This surgical procedure cuts or
destroys the sympathetic ganglia, collections of nerve
cell bodies in clusters along the thoracic or lumbar
spinal cord.

Purpose
The autonomic nervous system that controls
unwilled (involuntary) body functions, such as breathing, sweating, and blood pressure, are divided into the
sympathetic and the parasympathetic nervous systems. The sympathetic nervous system speeds the
heart rate, narrows (constricts) blood vessels, and
raises blood pressure. Blood pressure is controlled by
means of nerve cells that run through sheaths around
the arteries. The sympathetic nervous system can be
described as the ‘‘fight or flight’’ system because it
allows us to respond to danger by fighting off an
attacker or by running away. When danger threatens,
the sympathetic nervous system increases heart and
respiratory rate, increases blood flow to muscles, and
decreases blood flow to other areas, such as skin,
digestive tract, and limb veins. The net effect is an
increase in blood pressure.
Sympathectomy is performed to relieve intermittent constricting of blood vessels (ischemia) when the
fingers, toes, ears, or nose are exposed to cold
(Raynaud’s phenomenon). In Raynaud’s phenomenon, the affected extremities turn white, then blue,
and red as the blood supply is cut off. The color
changes are accompanied by numbness, tingling, burning, and pain. Normal color and feeling are restored
when heat is applied. The condition sometimes occurs
without direct cause but it is more often caused by an
underlying medical condition, such as rheumatoid
arthritis. Sympathectomy is usually less effective
3607

Sympathectomy

Resources

Sympathectomy

when Raynaud’s is caused by an underlying medical
condition. Narrowed blood vessels in the legs that
cause painful cramping (claudication) are also treated
with sympathectomy.
Sympathectomy may be helpful in treating reflex
sympathetic dystrophy (RSD), a condition that sometimes develops after injury. In RSD, the affected limb
is painful (causalgia) and swollen. The color, temperature, and texture of the skin change. These symptoms
are related to prolonged and excessive activity of the
sympathetic nervous system.
Because sweating is controlled by the sympathetic
nervous system, sympathectomy is also effective in
treating excessive sweating (hyperhidrosis) of the
palms, armpits, or face.

Precautions
To determine whether sympathectomy is needed,
a reversible block of the affected nerve cell (ganglion)
should be done. A reversible ganglion block interrupts
nerve impulses by means of steroid and anesthetic
injected into it. If the block has a positive effect on
pain and blood flow in the affected area, the sympathectomy will probably be helpful. The surgical
procedure should be performed only if conservative
treatment has not worked. Conservative treatment
includes avoiding exposure to stress and cold, physical
therapy, and medications.
Sympathectomy is most likely to be effective in
relieving the pain of reflex sympathetic dystrophy if it
is done soon after the injury occurs. However,
increased benefit from early surgery should be
balanced against time needed to promote spontaneous
recovery and response to conservative treatment.

Description
Sympathectomy was traditionally done as an
inpatient surgical procedure under general anesthesia.
An incision was made on the mid-back, exposing the
ganglia to be cut. Recent techniques are less invasive
and may be done under local anesthesia and as outpatient surgery. If only one arm or leg is affected, it
may be treated with a percutaneous radiofrequency
technique. In this technique, the surgeon locates the
ganglia by a combination of x ray and electrical stimulation. The ganglia are destroyed by applying radio
waves through electrodes on the skin.
Sympathectomy for hyperhidrosis can be done by
making a small incision under the armpit and introducing air into the chest cavity. The surgeon inserts a
fiber optic tube (endoscope) that projects an image of
3608

the operation on a video screen. The ganglia can then
be cut with fine scissors attached to the endoscope.
Laser beams can also be used to destroy the ganglia.

Preparation
As with any surgery, patients should discuss
expected results and possible risks with their surgeons.
They should tell their surgeons all medications they
are taking and all their medical problems, and they
should be in good general health. To improve general
health, the patient may be asked to lose weight, give up
smoking or alcohol, and get the proper sleep, diet, and
exercise. Immediately before the surgery, patients will
not be permitted to eat or drink, and the surgical site
will be cleaned and scrubbed.

Aftercare
The surgeon will inform the patient about specific
aftercare needed for the technique used. Doppler ultrasonography, a test using sound waves to measure blood
flow, can help to determine whether sympathectomy
has had a positive result.

Risks
Side effects of sympathectomy may include
decreased blood pressure while standing, which may
cause fainting spells. After sympathectomy in men,
semen is sometimes ejaculated into the bladder,
which may impair fertility. After a sympathectomy
done by inserting an endoscope in the chest cavity,
patients may experience chest pain with deep breathing. This problem usually disappears within two
weeks. They may also experience pneumothorax (air
in the chest cavity).
In 30% of cases, surgery for hyperhidrosis may
cause increased sweating on the chest. In 2% of cases,
this surgery causes increased sweating in other areas,
including increased facial sweating while eating. Other
complications occur less frequently. These complications include Horner’s syndrome, a condition of the
nervous system that causes the pupil of the eye to
close, the eyelid to droop, and sweating to decrease
on one side of the face. Other rare complications are
nasal blockage and pain of the nerves supplying the
skin between the ribs.

Normal results
Some studies report that sympathectomy relieves
causalgia in as many as 75% of cases. The studies also
show that it relieves hyperhidrosis in more than 90%
GALE ENCYCLOPEDIA OF MEDICINE

Causalgia—A severe burning sensation sometimes
accompanied by redness and inflammation of the
skin. Causalgia is caused by injury to a nerve outside the spinal cord.
Claudication—Cramping or pain in a leg caused by
poor blood circulation. This condition is frequently
caused by hardening of the arteries (atherosclerosis). Intermittent claudication occurs only at certain
times, usually after exercise, and is relieved by rest.
Fiberoptics—In medicine, fiberoptics uses glass or
plastic fibers to transmit light through a specially
designed tube. The tube is inserted into organs or
body cavities where it transmits a magnified image
of the internal body structures.
Hyperhidrosis—Excessive sweating. Hyperhidrosis
can be caused by heat, overactive thyroid glands,
strong emotion, menopause, or infection.
Parasympathetic nervous system—The division of
the autonomic (involuntary or unwilled) nervous
system that slows heart rate, increases digestive
and gland activity, and relaxes the sphincter muscles that close off body organs.
Percutaneous—Performed through the skin, from the
Latin per, meaning through and cutis, meaning skin.
Pneumothorax—A collection of air or gas in the
chest cavity that causes a lung to collapse.
Pneumothorax may be caused by an open chest
wound that admits air.

of cases. The less invasive procedures cause very little
scarring. Most patients stay in the hospital for less
than one day and return to work within the week.
Resources
OTHER

The American Institute for Hyperhidrosis Page. <http:/
www.handsweat.com>.

Laurie Barclay, MD

Syncope see Fainting
Syndactyly see Polydactyly and syndactyly
Synergistic gangrene see Flesh-eating disease
Synovial fluid analysis see Joint fluid analysis
Synovial membrane biopsy see Joint biopsy
GALE ENCYCLOPEDIA OF MEDICINE

Syphilis

KEY TERMS

Syphilis
Definition
Syphilis is an infectious systemic disease that may
be either congenital or acquired through sexual contact or contaminated needles.

Description
Syphilis has both acute and chronic forms that
produce a wide variety of symptoms affecting most
of the body’s organ systems. The range of symptoms
makes it easy to confuse syphilis with less serious
diseases and ignore its early signs. Acquired syphilis
has four stages (primary, secondary, latent, and tertiary) and can be spread by sexual contact during the
first three of these four stages.
Syphilis, which is also called lues (from a Latin
word meaning plague), has been a major public health
problem since the sixteenth century. The disease was
treated with mercury or other ineffective remedies
until World War I, when effective treatments based
on arsenic or bismuth were introduced. These were
succeeded by antibiotics after World War II. At that
time, the number of cases in the general population
decreased, partly because of aggressive public health
measures. This temporary decrease, combined with
the greater amount of attention given to AIDS in
recent years, leads some people to think that syphilis
is no longer a serious problem. In actual fact, the
number of cases of syphilis in the United States has
risen since 1980. This increase affects both sexes, all
races, all parts of the nation, and all age groups,
including adults over 60. The number of women of
childbearing age with syphilis is the highest that has
been recorded since the 1940s. About 25,000 cases of
infectious syphilis in adults are reported annually in
the United States. It is estimated, however, that
400,000 people in the United States need treatment
for syphilis every year, and that the annual worldwide
total is 50 million persons.
In 1999, the Centers for Disease Control and
Prevention (CDC) joined several other federal agencies in announcing the ‘‘National Plan to Eliminate
Syphilis in the United States.’’ Eliminating the disease
was defined as the absence of transmission of the
disease; that is, no transmission after 90 days following the report of an imported index case. The national
goals for eliminating syphilis include bringing the
annual number of reported cases in the United States
below 1000, and increasing the number of syphilis-free
counties to 90% by 2005. In November 2002, the CDC
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Syphilis

released figures for 2000–2001, which indicate that the
number of reported cases of primary and secondary
syphilis rose slightly. This rise, however, occurred only
among men who have sex with other men. The CDC
also stated that the number of new cases of syphilis has
actually declined among women as well as among nonHispanic blacks.
The increased incidence of syphilis since the 1970s
is associated with drug abuse as well as changes in
sexual behavior. The connections between drug
abuse and syphilis include needle sharing and exchanging sex for drugs. In addition, people using drugs are
more likely to engage in risky sexual practices. As of
2002, the risk of contracting syphilis is particularly
high among those who abuse crack cocaine.
With respect to changing patterns of conduct, a
sharp increase in the number of people having sex with
multiple partners makes it more difficult for public
health doctors to trace the contacts of infected persons. Women are not necessarily protected by having
sex only with other women; in the past few years,
several cases have been reported of female-to-female
transmission of syphilis through oral-genital contact.
In addition, the incidence of syphilis among men
who have sex with other men continues to rise.
Several studies in Latin America as well as in the
United States reported in late 2002 that unprotected
sexual intercourse is on the increase among gay and
bisexual men.
Changing patterns of sexual behavior have led to
a striking increase in the number of cases of syphilis in
eastern Europe since the collapse of the Soviet Union;
Slovenia reported an 18-fold increase in reported cases
of syphilis just between 1993 and 1994. Over half of the
new cases were linked to a source of infection in
another European country.
In general, high-risk groups for syphilis in the
United States and Canada include:


sexually active teenagers



people infected with another sexually transmitted
disease (STD), including AIDS



sexually abused children



women of childbearing age



prostitutes of either sex and their customers



prisoners



persons who abuse drugs or alcohol

The chances of contracting syphilis from an
infected person in the early stages of the disease during
unprotected sex are between 30–50%.
3610

Causes and symptoms
Syphilis is caused by a spirochete, Treponema pallidum. A spirochete is a thin spiral- or coil-shaped
bacterium that enters the body through the mucous
membranes or breaks in the skin. In 90% of cases,
the spirochete is transmitted by sexual contact.
Transmission by blood transfusion is possible but
rare; not only because blood products are screened
for the disease, but also because the spirochetes die
within 24 hours in stored blood. Other methods of
transmission are highly unlikely because T. pallidum
is easily killed by heat and drying.
Primary syphilis
Primary syphilis is the stage of the organism’s
entry into the body. The first signs of infection are
not always noticed. After an incubation period ranging between 10 and 90 days, the patient develops a
chancre, which is a small blister-like sore about 0.5 in
(13 mm) in size. Most chancres are on the genitals, but
may also develop in or on the mouth or on the breasts.
Rectal chancres are common in male homosexuals.
Chancres in women are sometimes overlooked if they
develop in the vagina or on the cervix. The chancres
are not painful and disappear in three to six weeks
even without treatment. They resemble the ulcers of
lymphogranuloma venereum, herpes simplex virus, or
skin tumors.
About 70% of patients with primary syphilis also
develop swollen lymph nodes near the chancre. The
nodes may have a firm or rubbery feel when the doctor
touches them but are not usually painful.
Secondary syphilis
Syphilis enters its secondary stage between six to
eight weeks and six months after the infection begins.
Chancres may still be present but are usually healing.
Secondary syphilis is a systemic infection marked by
the eruption of skin rashes and ulcers in the mucous
membranes. The skin rash may mimic a number of
other skin disorders such as drug reactions, rubella,
ringworm, mononucleosis, and pityriasis rosea.
Characteristics that point to syphilis include:


a coppery color



absence of pain or itching



occurrence on the palms of hands and soles of feet

The skin eruption may resolve in a few weeks or
last as long as a year. The patient may also develop
condylomata lata, which are weepy pinkish or grey
areas of flattened skin in the moist areas of the body.
GALE ENCYCLOPEDIA OF MEDICINE

About 50% of patients with secondary syphilis
develop swollen lymph nodes in the armpits, groin,
and neck areas; about 10% develop inflammations of
the eyes, kidney, liver, spleen, bones, joints, or the
meninges (membranes covering the brain and spinal
cord). They may also have a flulike general illness with
a low fever, chills, loss of appetite, headaches, runny
nose, sore throat, and aching joints.

NEUROSYPHILIS. About 8% of patients with
untreated syphilis will develop symptoms in the central nervous system that include both physical and
psychiatric symptoms. Neurosyphilis can appear at
any time, from 5-35 years after the onset of primary
syphilis. It affects men more frequently than women
and Caucasians more frequently than African
Americans.

Neurosyphilis is classified into four types:


Asymptomatic. In this form of neurosyphilis, the
patient’s spinal fluid gives abnormal test results but
there are no symptoms affecting the central nervous
system.



Meningovascular. This type of neurosyphilis is
marked by changes in the blood vessels of the brain
or inflammation of the meninges (the tissue layers
covering the brain and spinal cord). The patient
develops headaches, irritability, and visual problems.
If the spinal cord is involved, the patient may experience weakness of the shoulder and upper arm
muscles.



Tabes dorsalis. Tabes dorsalis is a progressive degeneration of the spinal cord and nerve roots. Patients
lose their sense of perception of one’s body position
and orientation in space (proprioception), resulting
in difficulties walking and loss of muscle reflexes.
They may also have shooting pains in the legs and
periodic episodes of pain in the abdomen, throat,
bladder, or rectum. Tabes dorsalis is sometimes
called locomotor ataxia.



General paresis. General paresis refers to the effects
of neurosyphilis on the cortex of the brain. The
patient has a slow but progressive loss of memory,
ability to concentrate, and interest in self-care.
Personality changes may include irresponsible behavior, depression, delusions of grandeur, or complete
psychosis. General paresis is sometimes called dementia paralytica, and is most common in patients
over 40.

Latent syphilis
Latent syphilis is a phase of the disease characterized by relative absence of external symptoms. The
term latent does not mean that the disease is not
progressing or that the patient cannot infect others.
For example, pregnant women can transmit syphilis to
their unborn children during the latency period.
The latent phase is sometimes divided into early
latency (less than two years after infection) and late
latency. During early latency, patients are at risk for
spontaneous relapses marked by recurrence of the
ulcers and skin rashes of secondary syphilis. In late
latency, these recurrences are much less likely. Late
latency may either resolve spontaneously or continue
for the rest of the patient’s life.
Tertiary syphilis
Untreated syphilis progresses to a third or tertiary
stage in about 35–40% of patients. Patients with tertiary syphilis cannot infect others with the disease. It is
thought that the symptoms of this stage are a delayed
hypersensitivity reaction to the spirochetes. Some
patients develop so-called benign late syphilis, which
begins between three and 10 years after infection and is
characterized by the development of gummas.
Gummas are rubbery tumor-like growths that are
most likely to involve the skin or long bones but may
also develop in the eyes, mucous membranes, throat,
liver, or stomach lining. Gummas are increasingly
uncommon since the introduction of antibiotics for
treating syphilis. Benign late syphilis is usually rapid
in onset and responds well to treatment.
CARDIOVASCULAR

SYPHILIS. Cardiovascular

syphilis occurs in 10–15% of patients who have progressed to tertiary syphilis. It develops between 10 and
25 years after infection and often occurs together with
neurosyphilis. Cardiovascular syphilis usually begins
as an inflammation of the arteries leading from the
heart and causes heart attacks, scarring of the aortic
valves, congestive heart failure, or the formation of an
aortic aneurysm.
GALE ENCYCLOPEDIA OF MEDICINE

Special populations
CONGENITAL SYPHILIS. Congenital syphilis has
increased at a rate of 400–500% over the past decade,
on the basis of criteria introduced by the Centers for
Disease Control (CDC) in 1990. In 1994, over 2,200
cases of congenital syphilis were reported in the
United States. The prognosis for early congenital
syphilis is poor: about 54% of infected fetuses die
before or shortly after birth. Those who survive may
look normal at birth but show signs of infection
between three and eight weeks later.

3611

Syphilis

The skin rashes, mouth and genital ulcers, and condylomata lata are all highly infectious.

Syphilis

Infants with early congenital syphilis have systemic symptoms that resemble those of adults with
secondary syphilis. There is a 40-60% chance that
the child’s central nervous system will be infected.
These infants may have symptoms ranging from jaundice, enlargement of the spleen and liver, and anemia
to skin rashes, condylomata lata, inflammation of the
lungs, ‘‘snuffles’’ (a persistent runny nose), and swollen lymph nodes.
CHILDREN. Children who develop symptoms after
the age of two years are said to have late congenital
syphilis. The characteristic symptoms include facial
deformities (saddle nose), Hutchinson’s teeth (abnormal upper incisors), saber shins, dislocated joints,
deafness, mental retardation, paralysis, and seizure
disorders.
PREGNANT WOMEN. Syphilis can be transmitted
from the mother to the fetus through the placenta at
any time during pregnancy, or through the child’s
contact with syphilitic ulcers during the birth process.
The chances of infection are related to the stage of the
mother’s disease. Almost all infants of mothers with
untreated primary or secondary syphilis will be
infected, whereas the infection rate drops to 40% if
the mother is in the early latent stage and 6–14% if she
has late latent syphilis.

Pregnancy does not affect the progression of
syphilis in the mother; however, pregnant women
should not be treated with tetracyclines.
HIV PATIENTS. Syphilis has been closely associated

with HIV infection since the late 1980s. Syphilis sometimes mimics the symptoms of AIDS. Conversely,
AIDS appears to increase the severity of syphilis in
patients suffering from both diseases, and to speed up
the development or appearance of neurosyphilis.
Patients with HIV are also more likely to develop
lues maligna, a skin disease that sometimes occurs in
secondary syphilis. Lues maligna is characterized by
areas of ulcerated and dying tissue. In addition, HIV
patients have a higher rate of treatment failure with
penicillin than patients without HIV.

This patient has secondary syphilis, evidenced by the
appearance of lesions on the skin. (Custom Medical Stock
Photo. Reproduced by permission.)

doctor. Women may be diagnosed in the course of a
gynecological checkup. Because of the long-term risks
of untreated syphilis, certain groups of people are now
routinely screened for the disease:


pregnant women



sexual contacts or partners of patients diagnosed
with syphilis



children born to mothers with syphilis



patients with HIV infection



persons applying for marriage licenses

When the doctor takes the patient’s history, he or
she will ask about recent sexual contacts in order to
determine whether the patient falls into a high-risk
group. Other symptoms, such as skin rashes or swollen
lymph nodes, will be noted with respect to the dates of
the patient’s sexual contacts. Definite diagnosis, however, depends on the results of laboratory blood tests.

Diagnosis
Patient history and physical diagnosis
The diagnosis of syphilis is often delayed because
of the variety of early symptoms, the varying length of
the incubation period, and the possibility of not noticing the initial chancre. Patients do not always connect
their symptoms with recent sexual contact. They may
go to a dermatologist when they develop the skin rash
of secondary syphilis rather than to their primary care
3612

Blood tests
There are several types of blood tests for syphilis
presently used in the United States. Some are used in
follow-up monitoring of patients as well as diagnosis.
NONTREPONEMAL ANTIGEN TESTS. Nontreponemal
antigen tests are used as screeners. They measure the
presence of reagin, which is an antibody formed in
reaction to syphilis. In the venereal disease research

GALE ENCYCLOPEDIA OF MEDICINE

additional diagnostic tests, particularly for congenital
syphilis and neurosyphilis.

The rapid plasma reagin (RPR) test works on the
same principle as the VDRL. It is available as a kit.
The patient’s serum is mixed with cardiolipin on a
plastic-coated card that can be examined with the
naked eye.

can also be confirmed by identifying spirochetes in
samples of tissue or lymphatic fluid. Fresh samples
can be made into slides and studied under darkfield
illumination. A newer method involves preparing
slides from dried fluid smears and staining them with
fluorescein for viewing under UV light. This method is
replacing darkfield examination because the slides can
be mailed to professional laboratories.

Nontreponemal antigen tests require a doctor’s
interpretation and sometimes further testing. They
can yield both false-negative and false-positive results.
False-positive results can be caused by other infectious
diseases, including mononucleosis, malaria, leprosy,
rheumatoid arthritis, and lupus. HIV patients have a
particularly high rate (4%, compared to 0.8% of HIVnegative patients) of false-positive results on reagin
tests. False-negatives can occur when patients are
tested too soon after exposure to syphilis; it takes
about 14-21 days after infection for the blood to
become reactive.
TREPONEMAL ANTIBODY TESTS. Treponemal antibody tests are used to rule out false-positive results
on reagin tests. They measure the presence of antibodies that are specific for T. pallidum. The most
commonly used tests are the microhemagglutination-T. pallidum (MHA-TP) and the fluorescent
treponemal antibody absorption (FTA-ABS) tests.
In the FTA-ABS, the patient’s blood serum is
mixed with a preparation that prevents interference
from antibodies to other treponemal infections.
The test serum is added to a slide containing
T. pallidum. In a positive reaction, syphilitic antibodies in the blood coat the spirochetes on the
slide. The slide is then stained with fluorescein,
which causes the coated spirochetes to fluoresce
when the slide is viewed under ultraviolet (UV)
light. In the MHA-TP test, red blood cells from
sheep are coated with T. pallidum antigen. The cells
will clump if the patient’s blood contains antibodies
for syphilis.

Treponemal antibody tests are more expensive
and more difficult to perform than nontreponemal
tests. They are therefore used to confirm the diagnosis of syphilis rather than to screen large groups of
people. These tests are, however, very specific and
very sensitive; false-positive results are relatively
unusual.
INVESTIGATIONAL BLOOD TESTS. Currently, ELISA,
Western blot, and PCR testing are being studied as

GALE ENCYCLOPEDIA OF MEDICINE

Other laboratory tests
MICROSCOPE STUDIES. The diagnosis of syphilis

SPINAL FLUID TESTS. Testing of cerebrospinal fluid
(CSF) is an important part of patient monitoring as
well as a diagnostic test. The VDRL and FTA-ABS
tests can be performed on CSF as well as on blood. An
abnormally high white cell count and elevated protein
levels in the CSF, together with positive VDRL
results, suggest a possible diagnosis of neurosyphilis.
CSF testing is not used for routine screening. It is used
most frequently for infants with congenital syphilis,
HIV-positive patients, and patients of any age who are
not responding to penicillin treatment.

Treatment
Medications
Syphilis is treated with antibiotics given either
intramuscularly (benzathine penicillin G or ceftriaxone) or orally (doxycycline, minocycline, tetracycline,
or azithromycin). Neurosyphilis is treated with a combination of aqueous crystalline penicillin G, benzathine penicillin G, or doxycycline. It is important
to keep the levels of penicillin in the patient’s tissues at
sufficiently high levels over a period of days or weeks
because the spirochetes have a relatively long reproduction time. Penicillin is more effective in treating the
early stages of syphilis than the later stages.
In the fall of 2000, the CDC convened a group of
medical advisors to discuss backup medications for
treating syphilis. Although none of the newer drugs
will displace penicillin as the primary drug, the doctors
recommended azithromycin and ceftriaxone as medications that should have a larger role in the treatment
of syphilis than they presently do.
Doctors do not usually prescribe separate medications for the skin rashes or ulcers of secondary syphilis. The patient is advised to keep them clean and dry,
and to avoid exposing others to fluid or discharges
from condylomata lata.
3613

Syphilis

laboratory (VDRL) test, a sample of the patient’s
blood is mixed with cardiolipin and cholesterol. If
the mixture forms clumps or masses of matter, the
test is considered reactive or positive. The serum sample can be diluted several times to determine the concentration of reagin in the patient’s blood.

Syphilis

Pregnant women should be treated as early in
pregnancy as possible. Infected fetuses can be cured
if the mother is treated during the second and third
trimesters of pregnancy. Infants with proven or suspected congenital syphilis are treated with either aqueous crystalline penicillin G or aqueous procaine
penicillin G. Children who acquire syphilis after
birth are treated with benzathine penicillin G.
Jarisch-Herxheimer reaction
The Jarisch-Herxheimer reaction, first described
in 1895, is a reaction to penicillin treatment that may
occur during the late primary, secondary, or early
latent stages. The patient develops chills, fever, headache, and muscle pains within two to six hours after
the penicillin is injected. The chancre or rash gets
temporarily worse. The Jarisch-Herxheimer reaction,
which lasts about a day, is thought to be an allergic
reaction to toxins released when the penicillin kills
massive numbers of spirochetes.

Alternative treatment
Antibiotics are essential for the treatment of
syphilis. Recovery from the disease can be assisted by
dietary changes, sleep, exercise, and stress reduction.

at one, three, six, and 12 months after treatment, or
until the results are negative. CSF should be examined
after one year. Patients with recurrences during the
latency period should be tested for reinfection.
The prognosis for patients with untreated syphilis
is spontaneous remission for about 30%; lifelong
latency for another 30%; and potentially fatal tertiary
forms of the disease in 40%.

Prevention
Immunity
Patients with syphilis do not acquire lasting
immunity against the disease. Currently, no effective
vaccine for syphilis has been developed. Prevention
depends on a combination of personal and public
health measures.
Lifestyle choices
The only reliable methods for preventing transmission of syphilis are sexual abstinence or monogamous relationships between uninfected partners.
Condoms offer some protection but protect only the
covered parts of the body.
Public health measures

Homeopathy
Homeopathic practitioners are forbidden by law
in the United States to claim that homeopathic treatment can cure syphilis. Given the high rate of syphilis
in HIV-positive patients, however, some alternative
practitioners who are treating AIDS patients with
homeopathic remedies maintain that they are beneficial for syphilis as well. The remedies suggested most
frequently are Medorrhinum, Syphilinum, Mercurius
vivus, and Aurum. The historical link between
homeopathy and syphilis is Hahnemann’s theory of
miasms. He thought that the syphilitic miasm was the
second oldest cause of constitutional weakness in
humans.

Prognosis
The prognosis is good for the early stages of
syphilis if the patient is treated promptly and given
sufficiently large doses of antibiotics. Treatment failures can occur and patients can be reinfected. There
are no definite criteria for cure for patients with primary and secondary syphilis, although patients who
are symptom-free and have had negative blood tests
for two years after treatment are usually considered
cured. Patients should be followed up with blood tests
3614

CONTACT TRACING. The law requires reporting of
syphilis cases to public health agencies. Sexual contacts of patients diagnosed with syphilis are traced and
tested for the disease. This includes all contacts for the
past three months in cases of primary syphilis and for
the past year in cases of secondary disease. Neither the
patients nor their contacts should have sex with anyone until they have been tested and treated.

Because of the rising incidence of syphilis abroad,
a growing number of public health physicians are
recommending routine screening of immigrants, refugees, and international adoptees for syphilis as of
late 2002.
All patients who test positive for syphilis should
be tested for HIV infection at the time of diagnosis.
PRENATAL TESTING OF PREGNANT WOMEN. Pregnant
women should be tested for syphilis at the time of their
first visit for prenatal care, and again shortly before
delivery. Proper treatment of secondary syphilis in the
mother reduces the risk of congenital syphilis in the
infant from 90% to less than 2%.

As of late 2005, many obstetricians and gynecologists are recommending routine screening of nonpregnant as well as pregnant women for syphilis. At
present, only about half of obstetricians and
GALE ENCYCLOPEDIA OF MEDICINE

Chancre—The initial skin ulcer of primary syphilis, consisting of an open sore with a firm or hard
base.
Condylomata lata—Highly infectious patches of
weepy pink or gray skin that appear in the moist
areas of the body during secondary syphilis.
Darkfield—A technique of microscope examination in which light is directed at an oblique angle
through the slide so that organisms look bright
against a dark background.
General paresis—A form of neurosyphilis in which
the patient’s personality, as well as his or her control of movement, is affected. The patient may
develop convulsions or partial paralysis.
Gumma—A symptom that is sometimes seen in
tertiary syphilis, characterized by a rubbery swelling or tumor that heals slowly and leaves a scar.
Index case—The first case of a contagious disease
in a group or population that serves to call attention
to the presence of the disease.
Jarisch-Herxheimer reaction—A temporary reaction to penicillin treatment for syphilis that includes
fever, chills, and worsening of the skin rash or
chancre.
Lues maligna—A skin disorder of secondary syphilis in which areas of ulcerated and dying tissue are
formed. It occurs most frequently in HIV-positive
patients.
Spirochete—A type of bacterium with a long, slender, coiled shape. Syphilis is caused by a
spirochete.
Tabes dorsalis—A progressive deterioration of the
spinal cord and spinal nerves associated with tertiary syphilis.

gynecologists in the United States screen nonpregnant
women for chlamydia and gonorrhea, while fewer than
a third screen them for syphilis.
EDUCATION AND INFORMATION. Patients diagnosed with syphilis should be given information
about the disease and counseling regarding sexual
behavior and the importance of completing antibiotic
treatment. It is also important to inform the general
public about the transmission and early symptoms of
syphilis, and provide adequate health facilities for
testing and treatment.

GALE ENCYCLOPEDIA OF MEDICINE

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Syphilis.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Augenbraun, M. H. ‘‘Treatment of Syphilis 2001:
Nonpregnant Adults.’’ Clinical Infectious Diseases 35,
Supplement 2 (October 15, 2002): S187–S190.
Campos-Outcalt, D., and S. Hurwitz. ‘‘ Female-to-Female
Transmission of Syphilis: A Case Report.’’ Sexually
Transmitted Diseases 29 (February 2002): 119–120.
Centers for Disease Control. ‘‘Primary and Secondary
Syphilis—United States, 2000-2001.’’ Morbidity and
Mortality Weekly Report 51 (November 1, 2002): 971–
973.
Dennis, L. K., and D. V. Dawson. ‘‘Meta-Analysis of
Measures of Sexual Activity and Prostate Cancer.’’
Epidemiology 13 (January 2002): 72–79.
Gibbs, R. S. ‘‘The Origins of Stillbirth: Infectious Diseases.’’
Seminars in Perinatology 26 (February 2002): 75–78.
Grgic-Vitek, M., I Klavs, M. Potocnik, and M. Rogl-Butina.
‘‘Syphilis Epidemic in Slovenia Influenced by Syphilis
Epidemic in the Russian Federation and Other Newly
Independent States.’’ International Journal of STD and
AIDS 13, Supplement 2 (December 2002): 2–4.
Hagedorn, H. J., A. Kraminer-Hagedorn, K. de Bosschere,
et al. ‘‘Evaluation of INNO-LIA Syphilis Assay as a
Confirmatory Test for Syphilis.’’ Journal of Clinical
Microbiology 40 (March 2002): 973–978.
Hogben, M., J. S. Lawrence, D. Kasprzyk, et al. ‘‘Sexually
Transmitted Disease Screening by United States
Obstetricians and Gynecologists.’’ Obstetrics and
Gynecology 100 (October 2002): 801–807.
Kolivras, A., J. de Maubeuge, M. Song, et al. ‘‘A Case of
Early Congenital Syphilis.’’ Dermatology 204 (2002):
338–340.
Pao, D., B. T. Goh, and J. S. Bingham. ‘‘Management Issues
in Syphilis.’’ Drugs 62 (2002): 1447–1461.
Ross, M. W., L. Y. Hwang, C. Zack, et al. ‘‘Sexual Risk
Behaviours and STIs in Drug Abuse Treatment
Populations Whose Drug of Choice is Crack Cocaine.’’
International Journal of STD and AIDS 13 (November
2002): 769–774.
Stauffer, W. M., D. Kamat, and P. F. Walker. ‘‘Screening of
International Immigrants, Refugees, and Adoptees.’’
Primary Care 29 (December 2002): 879–905.
Sutmoller, F., T. L. Penna, C. T. de Souza, et al. ‘‘Human
Immunodeficiency Virus Incidence and Risk Behavior
in the ‘Projeto Rio’: Results of the First 5 Years of the
Rio de Janeiro Open Cohort of Homosexual and
Bisexual Men, 1994–98.’’ International Journal of
Infectious Diseases 6 (December 2002): 259–265.
Whittington, W. L., T. Collis, C. Dithmer-Schreck, et al.
‘‘Sexually Transmitted Diseases and Human
Immunodeficiency Virus-Discordant Partnerships
3615

Syphilis

Resources

KEY TERMS

Systemic lupus erythematosus

Among Men Who Have Sex With Men.’’ Clinical
Infectious Diseases 35 (October 15, 2002): 1010–1017.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rebecca J. Frey, PhD

Systemic antifungal drugs see Antifungal
drugs, systemic

Systemic lupus erythematosus
Definition
Systemic lupus erythematosus (also called lupus
or SLE) is a disease where a person’s immune system
attacks and injures the body’s own organs and tissues.
Almost every system of the body can be affected by
SLE.

Description
The body’s immune system is a network of cells
and tissues responsible for clearing the body of invading foreign organisms, like bacteria, viruses, and fungi.
Antibodies are special immune cells that recognize
these foreign invaders, and begin a chain of events to
destroy them. In an autoimmune disorder like SLE, a
person’s antibodies begin to recognize the body’s own
tissues as foreign. Cells and chemicals of the immune
system damage the tissues of the body. The reaction
that occurs in tissue is called inflammation.
Inflammation includes swelling, redness, increased
blood flow, and tissue destruction.

A close-up view of a woman’s face with a lesion caused by
systemic lupus erythematosus (SLE). One characteristic of
this autoimmune disease is a butterfly rash present across
the cheeks and nose. (Photograph by Dr. P. Marazzi, Custom
Medical Stock Photo. Reproduced by permission.)

Occasionally, medications can cause a syndrome
of symptoms very similar to SLE. This is called
drug-induced lupus. Medications that may cause this
syndrome include hydralazine (used for high blood
pressure) and procainamide (used for abnormal heartbeats). Drug-induced lupus almost always disappears
after the patient stops taking the medications that
caused it.

Causes and symptoms

In SLE, some of the common antibodies that
normally fight diseases are thought to be out of control. These include antinuclear antibodies and antiDNA antibodies. Antinuclear antibodies are directed
against the cell’s central structure that contains genetic
material (the nucleus). Anti-DNA antibodies are
directed against the cell’s genetic material. DNA is
the chemical substance that makes up the chromosomes and genes.

The cause of SLE is unknown. Because the vast
majority of patients are women, some research is being
done to determine what (if any) link the disease has to
female hormones. SLE may have a genetic basis,
although more than one gene is believed to be involved
in the development of the disease. Because patients
with the disease may suddenly have worse symptoms
(called a flare) after exposure to things like sunlight,
alfalfa sprouts, and certain medications, researchers
suspect that some environmental factors may also be
at work.

SLE can occur in both males and females of all
ages, but 90% of patients are women. The majority of
these women are in their childbearing years. African
Americans are more likely than Caucasians to develop
SLE.

The severity of a patient’s SLE varies over time.
Patients may have periods with mild or no symptoms,
followed by a flare. During a flare, symptoms increase
in severity and new organ systems may become
affected.

3616

GALE ENCYCLOPEDIA OF MEDICINE

Many of the symptoms and laboratory test results of
SLE patients are similar to those of patients with
different diseases, including rheumatoid arthritis, multiple sclerosis, and various nervous system and blood
disorders.



Joints. Joint pain and problems, including arthritis,
are very common. About 90% of all SLE patients
have these types of problems.



Skin. A number of skin rashes may occur, including
a red butterfly-shaped rash that spreads across
the face. The ‘‘wings’’ of the butterfly appear across
the cheekbones, and the ‘‘body’’ appears across the
bridge of the nose. A discoid, or coin-shaped, rash
causes red, scaly bumps on the cheeks, nose, scalp,
ears, chest, back, and the tops of the arms and legs.
The roof of the mouth may develop sore, irritated
pits (ulcers). Hair loss is common. SLE patients tend
to be very easily sunburned (photosensitive).

Laboratory tests that are helpful in diagnosing
SLE include several tests for a variety of antibodies
commonly elevated in SLE patients (including antinuclear antibodies, anti-DNA antibodies, etc.). SLE
patients tend to have low numbers of red blood cells
(anemia) and low numbers of certain types of white
blood cells. The erythrocyte sedimentation rate (ESR),
a measure of inflammation in the body, tends to be
quite elevated. Samples of tissue (biopsies) from
affected skin and kidneys show characteristics of the
disease.



When Lungs. Inflammation of the tissues that cover
the lungs and line the chest cavity causes pleuritis, with
fluid accumulating in the lungs. The patient frequently
experiences coughing and shortness of breath.



Heart and circulatory system. Inflammation of the
tissue surrounding the heart causes pericarditis;
inflammation of the heart itself causes myocarditis.
These heart problems may result in abnormal beats
(arrhythmias), difficulty pumping the blood strongly
enough (heart failure), or even sudden death. Blood
clots often form in the blood vessels and may lead to
complications.



Nervous system. Headaches, seizures, changes in
personality, and confused thinking (psychosis) may
occur.



Kidneys. The kidneys may suffer significant destruction, with serious life-threatening effects. They may
become unable to adequately filter the blood, leading
to kidney failure.



Gastrointestinal system. Patients may experience
nausea, vomiting, diarrhea, and abdominal pain.
The lining of the abdomen may become inflamed
(peritonitis).



Eyes. The eyes may become red, sore, and dry.
Inflammation of one of the nerves responsible for
vision may cause vision problems, and blindness
can result from inflammation of the blood vessels
(vasculitis) that serve the retina.

Diagnosis
Diagnosis of SLE can be somewhat difficult.
There are no definitive tests for diagnosing SLE.
GALE ENCYCLOPEDIA OF MEDICINE

A test called the lupus erythematosus cell preparation (or LE prep) test is also performed. This test
involves obtaining a sample of the patient’s blood.
Cells from the blood are damaged in the laboratory
in order to harvest their nuclei. These damaged cells
are then put together with the patient’s blood serum,
the liquid part of blood separated from the blood cells.
Antinuclear antibodies within the patient’s serum will
clump together with the damaged nuclear material. A
material called Wright’s stain will cause these clumps
to turn blue. These stained clumps are then reacted
with some of the patient’s white blood cells, which will
essentially eat the clumps. LE cells are the white blood
cells that contain the blue clumps. This test will be
positive in about 70-80% of all patients with SLE.
The American Rheumatism Association developed a list of symptoms used to diagnose SLE.
Research supports the idea that people who have at
least four of the eleven criteria (not necessarily simultaneously) are extremely likely to have SLE. The criteria are:


butterfly rash



discoid rash



photosensitivity



mouth ulcers



arthritis



inflammation of the lining of the lungs or the lining
around the heart



kidney damage, as noted by the presence of protein
or other abnormal substances called casts in the urine



seizures or psychosis



the presence of certain types of anemia and low
counts of particular white blood cells
3617

Systemic lupus erythematosus

Many SLE patients have fevers, fatigue, muscle
pain, weakness, decreased appetite, and weight loss.
The spleen and lymph nodes are often swollen and
enlarged. The development of other symptoms in
SLE varies, depending on the organs affected.

Systemic lupus erythematosus

CNS
Seizures

Skin
Butterfly rash
Discoid lupus

Heart
Endocarditis
Myocarditis

Serositis
Pleuritis
Pericarditis

Hematologic effects
Hemolytic anemia
Leukopenia
Thrombocytopenia

Glomerulonephritis

Arthritis

Lymphadenophathy

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the individual’s immune system attacks, injures, and
destroys the body’s own organs and tissues. Nearly every system of the body can be affected by SLE, as depicted in the
illustration above. (Illustration by Electronic Illustrators Group.)



the presence of certain immune cells, anti-DNA antibodies, or a falsely positive test for syphilis



the presence of antinuclear antibodies

Treatment
Treatment depends on the organ systems affected
by SLE and the severity of the disease. Some patients
have a mild form of SLE. Their mild symptoms of
inflammation can be treated with nonsteroidal antiinflammatory drugs like ibuprofen (Motrin, Advil)
and aspirin. Severe skin rashes and joint problems
may respond to a group of medications usually used
to treat malaria. More severely ill patients with
potentially life-threatening complications (including
3618

kidney disease, pericarditis, or nervous system complications) will require treatment with more potent
drugs, including steroid medications. Because steroids have serious side effects, they are reserved for
more severe cases of SLE. Drugs that decrease the
activity of the immune system (called immunosuppressant drugs) may also be used for severely ill SLE
patients.
These
include
azathioprine
and
cyclophosphamide.
Other treatments for SLE try to help specific
symptoms. Clotting disorders will require blood thinners. Psychotic disorders will require specific medications. Kidney failure may require the blood to be
cleaned outside the body through a machine (dialysis)
or even a kidney transplantation.
GALE ENCYCLOPEDIA OF MEDICINE

Autoimmune disorder—A disorder in which the
body’s antibodies mistake the body’s own tissues
for foreign invaders. The immune system then
attacks and causes damage to these tissues.
Chromosomes—Spaghetti-like structures located
within the nucleus (or central portion) of each
cell. Chromosomes contain genes, structures that
direct the growth and functioning of all the cells
and systems in the body. Chromosomes are responsible for passing on hereditary traits from parents to
child.
Immune system—The system of specialized
organs, lymph nodes, and blood cells throughout
the body that work together to prevent foreign
organisms (bacteria, viruses, fungi, etc.) from
invading the body.
Psychosis—Extremely disordered thinking with a
poor sense of reality; may include hallucinations
(seeing, hearing, or smelling things that are not
really there).

Alternative treatment
A number of alternative treatments have been
suggested to help reduce the symptoms of SLE.
These include acupuncture and massage for relieving
the pain of sore joints and muscles. Stress management is key for people with SLE and such techniques
as meditation, hynotherapy, and yoga may be helpful
in promoting relaxation. Dietary suggestions include
eating a whole foods diet with reduced amounts of red
meat and dairy products in order to decrease pain and
inflammation. Food allergies are believed either to
contribute to SLE or to arise as a consequence of the
digestive difficulties. Wheat, dairy products, and soy
are the major offenders. An elimination/challenge diet
can help identify the offending foods so that they can
be avoided. Another dietary measure that may be
beneficial is eating more fish that contain omega-3
fatty acids, like mackerel, sardines, and salmon.
Because alfalfa sprouts have been associated with the
onset of flares in SLE, they should be avoided.
Supplements that have been suggested to improve
the health of SLE patients include vitamins B, C, and
E, as well as selenium, zinc, magnesium, and a complete trace mineral supplement. Vitamin A is believed
to help improve discoid skin rashes. Botanical medicine can help the entire body through immune modulation and detoxification, as well as assisting
GALE ENCYCLOPEDIA OF MEDICINE

individual organs and systems. Homeopathy and
flower essences can work deeply on the emotional
level to help people with this difficult disease.

Prognosis
The prognosis for patients with SLE varies,
depending on the organ systems most affected and
the severity of inflammation. Some patients have
long periods of time with mild or no symptoms.
About 90-95% of patients are still living after 2 years
with the disease. About 82-90% of patients are still
living after 5 years with the disease. After 10 years,
71-80% of patients are still alive, and 63-75% are still
alive after 20 years. The most likely causes of death
during the first 10 years include infections and kidney
failure. During years 11-20 of the disease, the most
likely cause of death involves the development of
abnormal blood clots.
Because SLE frequently affects women of childbearing age, pregnancy is an important issue. For
pregnant SLE patients, about 30% of the pregnancies
end in miscarriage. About 25% of all babies born to
mothers with SLE are premature. Most babies born to
mothers with SLE are normal. However, a rare condition called neonatal lupus causes a baby of a mother
with SLE to develop a skin rash, liver or blood problems, and a serious heart condition.

Prevention
There are no known ways to avoid developing
SLE. However, it is possible for a patient who has
been diagnosed with SLE to prevent flares of the disease. Recommendations for improving general health
to avoid flares include decreasing sun exposure, getting sufficient sleep, eating a healthy diet, decreasing
stress, and exercising regularly. It is important for a
patient to try to identify the early signs of a flare (like
fever, increased fatigue, rash, headache). Some people
believe that noticing and responding to these warning
signs will allow a patient with SLE to prevent a flare,
or at least to decrease its severity.
Resources
ORGANIZATIONS

American College of Rheumatology. 1800 Century Place,
Suite 250, Atlanta, GA 30345. (404) 633-3777. <http://
www.rheumatology.org>.
Lupus Foundation of America. 1300 Piccard Dr., Suite 200,
Rockville, MD 20850. (800) 558-0121. <http://
www.lupus.org>.

Rosalyn Carson-DeWitt, MD
3619

Systemic lupus erythematosus

KEY TERMS

T
T-cell count see Lymphocyte typing
T-PA see Thrombolytic therapy
Taeniasis see Tapeworm diseases
Tagged red blood cell scan see GI bleeding
studies

Tai chi
Definition
T’ai chi is a Chinese exercise system that uses
slow, smooth body movements to achieve a state of
relaxation of both body and mind.

Purpose
As a system of physical exercise used to improve
and maintain health, t’ai chi can be helpful in achieving
a state of physical and mental relaxation while also
strengthening the cardiovascular and immune systems.

Precautions
As a very slow and gentle form of moving, tai chi
has virtually no side effects. However, if a person has
any doubts about the conditions of his or her joints,
vertebrae, or heart, a physician should be consulted.

Description
Developed originally in China as a self-defense
strategy, or martial art, tai chi—the ‘‘supreme ultimate
fist’’—is practiced in modern times primarily as a
gentle exercise technique. Described as ‘‘meditation
in motion,’’ tai chi consists of a standing person performing a series of postures or bodily movements in a
GALE ENCYCLOPEDIA OF MEDICINE

slow and graceful manner, with each movement flowing without pause to the next. According to Chinese
legend, the technique was created by a Taoist monk
who was inspired as he watched a crane and a snake do
battle. Impressed by the ‘snake’s ability to subtly and
swiftly avoid the bird’s thrusts, he devised a series of
self-defense techniques that do not involve meeting the
opponent’s force with force, but rather stress evading
the blow; causing the opponent’s own momentum to
work against him.
Tai chi is an ancient form of exercise, about 2,000
years old, that at one point had over 100 separate
movements or postures. In current practice, there are
two popular versions, of 18 and 37 movements respectively. The fact that in China 10 million people practice some type of t’ai chi daily suggests that it is the one
of the most popular forms of exercise in the world. In
the United States, t’ai chi is learned in classes in which
students (or ‘‘players,’’ as they are called in China)
wear loose, comfortable clothing and either go barefoot or wear only socks or soft shoes on the feet. In
China, t’ai chi is almost always practiced outdoors at
dawn, and ideally near trees. Unlike other martial arts,
t’ai chi is not competitive. Classes usually begin with a
few minutes of standing meditation to calm the mind
and gather energy. Following warm-up exercises, students are taught the basics of a particular form or
posture. Learning forms is not easy, and it takes
some time to master what looks like a simple position.
Properly done postures are done in a relaxed, artful,
and linked way, with the circular and rhythmic movements of one position flowing seamlessly into the next.
While strict attention to body position is critical,
proper breathing is considered to be equally important. Just as movements are slow and continuous
and without strain, breathing should be effortless
yet deep. Finally, both mental and physical balance
is considered essential to t’ai chi. The experienced
3621

Tai chi

KEY TERMS
Arthritis—Inflammation of the joints.
Cardiovascular—Relating to the heart and blood
vessels.
Continuity—Uninterrupted and successive.
Fibromyalgia—A chronic disease syndrome characterized by fatigue, widespread muscular soreness,
and pain at specific points on the body.
Meditation—An exercise of contemplation that
induces a temporary feeling of relaxation.
Stamina—Staying power, endurance.
Yoga—A system of exercise aimed at promoting the
control of the body and the mind.

Tai chi is a Chinese exercise system which uses slow,
smooth body movements to achieve a state of relaxation.
The posture above is part of the single whip sequence of Tai
chi motions. (Illustration by Electronic Illustrators Group.)

practitioner of t’ai chi maintains perfect body balance
throughout the exercise series. Altogether, the five
essential qualities of t’ai chi are:


Slowness. To develop awareness.



Lightness. To make movements flow.



Balance. To prevent body strain.



Calmness. To maintain continuity.



Clarity. To focus the mind.

T’ai chi has both physical and mental benefits. If
done regularly, it improves muscle tone, flexibility,
balance, and coordination. Many older people find
that it boosts their energy, stamina, and agility, sharpens their reflexes, and gives an overall sense of wellbeing. The calming and meditative aspects of t’ai chi
allow many to experience its ability to relieve stress.
Some claim t’ai chi to be a healing therapy, and it is
often used to support other treatments for chronic
conditions; arthritis, fibromyalgia, and digestive disorders are just three examples. Like yoga, t’ai chi has
several different styles to suit the individual. Also, it
can eventually be done daily by oneself, and ultimately
becomes a very personal endeavor. Most Westerners
find it best to practice t’ai chi in the same place and at
the same time of day; and those who enjoy it most are
those who are not seeking major, dramatic breakthroughs, but rather who can take pleasure in small
gains that accumulate over a long period of time.
3622

Some research done in the United States focuses on
the emotional and psychological benefits of t’ai chi. One
recently discovered advantage of t’ai chi is its ability to
hold people’s interest longer than many other forms of
exercise. One study in Oregon found that only 20% of
people enrolled in a six-month t’ai chi program dropped
out before the end, compared to an average of 55% for
other forms of exercise. With regard to depression, a
study of college students found that those who were
taking t’ai chi classes had a lower rate of depression
than students enrolled in other fitness programs.

Risks
T’ai chi is a safe exercise system for people of all
ages and fitness levels. Done properly, without any
over-stretching, t’ai chi should not leave a person feeling tired or sore.

Normal results
Besides its overall fitness benefits and stress reduction aspects, regular t’ai chi sessions are said to be
especially helpful for seniors, as they lower their
blood pressure. T’ai chi claims to benefit arthritis
sufferers, those recovering from an injury or rehabilitating their hearts, and also improves balance, and
therefore, reduces the risk of falling, especially important for the elderly. T’ai chi can result in a significant
improvement in the quality of life for anyone. But,
because of the low stress level of the exercises it is a
particularly attractive form of exercise to seniors.
In addition to studying the cardiovascular and
range-of-motion benefits of t’ai chi, researchers are
GALE ENCYCLOPEDIA OF MEDICINE

Tailbone injuries see Coccyx injuries

Tapeworm diseases

also investigating its positive effects on the immune
system. A team of scientists in California reported in
2003 that t’ai chi boosts the resistance of older people
to the shingles virus— a virus that is both more common and more severe in the elderly.

Talipes see Clubfoot
Tamoxifen see Anticancer drugs
Tamponade see Cardiac tamponade

Resources
BOOKS

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I: Sound Mind, Sound Body. New York: Simon &
Schuster, 2002.
PERIODICALS

Christou, E. A., Y. Yang, and K. S. Rosengren. ‘‘Taiji
Training Improves Knee Extensor Strength and Force
Control in Older Adults.’’ Journals of Gerontology,
Series A: Biological Sciences and Medical Sciences 58
(August 2003): 763–766.
Cooper, Bob. ‘‘An Exercise in Vitality: Put Away Your
Prejudices— T’ai Chi Ain’t Just for Senior Citizens and
Vegans.’’ Men’s Fitness 18 (September 2002): 86-91.
Filusch Betts, Elaine. ‘‘The Effect of t’ai Chi on
Cardiorespiratory Function in Patients with Coronary
Artery Bypass Surgery.’’ Physical Therapy September
1999.
Irwin, M. R., J. L. Pike, J. C. Cole, and M. N. Oxman.
‘‘Effects of a Behavioral Intervention, T’ai Chi Chih, on
Varicella-Zoster Virus Specific Immunity and Health
Functioning in Older Adults.’’ Psychosomatic Medicine
65 (September-October 2003): 824–830.
Li, F., K. J. Fisher, P. Harmer, and E. McAuley.
‘‘Delineating the Impact of T’ai Chi Training on
Physical Function Among the Elderly.’’ American
Journal of Preventive Medicine 23 (August 2002): 92-97.
Song, R., E. O. Lee, P. Lam, and S. C. Bae. ‘‘Effects of T’ai
Chi Exercise on Pain, Balance, Muscle Strength, and
Perceived Difficulties in Physical Functioning in Older
Women with Osteoarthritis: A Randomized Clinical
Trial.’’ Journal of Rheumatology 30 (September 2003):
2039–2044.
Taggart, H. M., C. L. Arslanian, S. Bae, and K. Singh.
‘‘Effects of T’ai Chi Exercise on Fibromyalgia
Symptoms and Health-Related Quality of Life.’’
Orthopaedic Nursing 22 (September-October 2003):
353–360.
ORGANIZATIONS

American Association of Oriental Medicine. 5530 Wisconsin
Avenue, Suite 1210, Chevy Chase, MD 20815. (301)
941-1064. <www.aaom.org>.
Canadian Taijiquan Federation. P.O. Box 421, Milton,
Ontario L9T 4Z1. <www
.canadiantaijiquanfederation.ca>.
Northeastern Tai Chi Chuan Association. 163 West 23rd St.,
5th Floor., New York, NY 10011 (212) 741-1922.

Leonard C. Bruno, PhD
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Tapeworm diseases
Definition
Tapeworms are a group of parasitic worms that
live in the intestinal tracts of some animals. Several
different species of tapeworms can infect humans.
Tapeworm disease or cestodiasis occurs most commonly after eating raw or undercooked meat or fish
that contains the immature form of the tapeworm.

Description
Tapeworm infections pose a serious public health
problem in many less developed countries due to poor
sanitation conditions. The disease is most common
where livestock, such as cattle and pigs, are raised in
areas where human feces are not disposed of in a
sanitary manner. Another common source of human
tapeworms are certain species of freshwater fish.
Tapeworm infections tend to occur more frequently
in areas of the world where the people regularly eat
raw or undercooked beef, pork, or fish. Persons of all
ages and both sexes are susceptible to tapeworm infection, but children are generally not exposed until they
are old enough to begin eating meat or fish.
Tapeworm infections in humans are less common
in industrialized regions of the world, although
German public health experts reported in 2003 that
the rate of these infections is higher in Europe than the
official statistics indicate. Travel to areas where tapeworm infections are more common and immigration
of people from these areas serve as new sources of the
parasite. Infected persons are often unaware of the
presence of adult tapeworms in their intestinal tract,
as they may have no obvious symptoms of infection.
Some tapeworms can live in an infected person for
over 10 years if diagnosis is not made and treatment
is not administered.
In addition to the typical infection caused by eating
undercooked meat or fish, people may also be directly
infected by ingesting tapeworm eggs shed by the adult
worm. This type of tapeworm infection can lead to a
condition referred to as cysticercosis, in which the
3623

Tapeworm diseases

larvae continue to develop within tissues other than the
intestinal tract. One of the most serious forms of this
disease occurs when the tapeworm larvae infect the
central nervous system, a disease referred to as neurocysticercosis. In contrast to a typical tapeworm infection, which may not be associated with symptoms,
neurocysticercosis is a serious condition that may
cause seizures and is potentially life-threatening.

Causes and symptoms
Several species of tapeworm can infect people.
The two most common species are the pork tapeworm
(Taenia solium) and the beef tapeworm (Taenia saginata). Improperly treated human sewage may be used
to fertilize pastures or crops. Pigs or cattle become
infected by grazing in contaminated pastures or drinking water contaminated with tapeworm eggs from
human feces. The pea-sized larvae of these tapeworms
are deposited in certain tissues of the body of infected
pigs and cattle, including the muscles. The infection is
then transmitted to people when raw or undercooked
meat containing tapeworm larvae is consumed. The
immature tapeworm develops into the adult form in
the human intestine and may remain there for many
years if not identified and treated.
The Taenia tapeworms attach to the intestinal
walls but cause only mild inflammation at the site of
attachment. As a result, most tapeworm carriers show
no symptoms (asymptomatic) and usually become
aware of the infection only after noticing tapeworm
segments in their feces. Segments of the beef tapeworm
may spontaneously pass through the anus causing a
noticeable sensation. Mild gastrointestinal symptoms,
such as nausea or abdominal pain, can occur in
infected individuals. In rare cases where the tapeworm
segments migrate into the appendix, pancreas, or bile
duct, there may be a sudden onset of severe abdominal
discomfort.
Cysticercosis is a potentially serious complication
of Taenia solium infection in which the larvae develop
outside the intestinal tract. This type of infection is less
common and occurs following accidental consumption of tapeworm eggs released from the adult worm.
These eggs initially are localized in the anal area, but
they may also contaminate the fingers or other parts of
the body. Infection can occur in the person harboring
the adult tapeworm or in other people with whom that
individual comes in contact. The tapeworm larvae
may develop in various tissues throughout the body.
The most serious clinical problems occur when the
larvae develop in the central nervous system (neurocysticercosis), potentially causing seizures and other
3624

neurological problems. An important aspect of this
type of infection is that poor hygiene on the part of
the individuals harboring an adult tapeworm can lead
to an infection in an individual who may never consume meat. This is a particular problem if infected
individuals are employed as food handlers.
Another important tapeworm that may infect
people is the fish tapeworm (Diphyllobothrium
latum). This is a frequent human intestinal parasite in
many areas where raw freshwater fish is consumed.
Human infection with the fish tapeworm is referred to
as diphyllobothriasis. Feces from infected hosts or raw
sewage contaminates a fresh water source. Tapeworm
larvae are initially ingested by freshwater crustaceans
and then are eaten by fish. Human infection occurs
when a person consumes raw fish contaminated with
the tapeworm larvae. Adult tapeworms then develop
in the human intestinal tract.
Most infections with the fish tapeworm are not
associated with symptoms. The tapeworm causes little
damage to the lining of the intestine. Infected individuals may report diarrhea, fatigue, weakness, or sensation of hunger more commonly than uninfected
individuals. One problem unique to this tapeworm is
that it may compete with the host for absorption of
vitamin B12 from the small intestine, causing the person to become deficient in this vitamin and leading to a
condition called pernicious anemia.
Two smaller species of tapeworms may also infect
people. The dwarf tapeworm (Hymenolepis nana) is a
common infection throughout the world that can be
passed from one person to another. Transmission is
usually the result of inadvertent ingestion of tapeworm eggs from feces eliminated by infected individuals. As a result, infection with this tapeworm is
encountered most frequently in children, the developmentally disabled, and psychiatric patient populations. Abdominal pain that is not localized to any
particular area is the most common complaint.
Patients may experience loose bowel movements or
diarrhea with mucus, but bloody diarrhea is rare.
Another small tapeworm capable of infecting people is the rodent tapeworm (Hymenolepis diminuta).
Rats, mice, and other rodents are the usual hosts for
the adult tapeworm (definitive host), but humans can
become infected following accidental consumption of
insects containing tapeworm larvae. Meal worms or
grain beetles that infest cereal, flour, or dried fruit are
the most likely source of infection. Most human infections are not associated with symptoms, although
some individuals report headaches, anorexia, nausea,
and diarrhea.
GALE ENCYCLOPEDIA OF MEDICINE

Ultrasound imaging is also being used as of 2003
to diagnose tapeworm infections. Because of the
recent rise in immigration and travel, clinicians in
developed countries are seeing more patients with
tapeworms. The World Health Organization (WHO)
has developed standardized sets of ultrasound images
to help doctors recognize the signs of a parasitic infection. In some cases, ultrasound allows the doctor to
see the tapeworm directly.

Treatment
The head of an adult beef tapeworm. (Custom Medical Stock
Photo. Reproduced by permission.)

Diagnosis
Identification of tapeworm segments or eggs in a
stool sample is necessary for diagnosis of an adult
tapeworm infection. In many cases, a tentative diagnosis may be made on the basis of a patient’s description of short chains of tapeworm segments in their
stool. Further evaluation is recommended to determine the actual species involved since infection with
Taenia solium is potentially more serious due to the
added risk of cysticercosis. Whenever possible, tapeworm segments should be carefully collected in water
or salt solutions, using strict precautions to avoid
contamination. Stool examination should be performed in a laboratory having experience in the diagnosis of intestinal parasites. It is recommended that at
least three stool samples be collected on alternate days
to increase the likelihood of being able to make an
accurate diagnosis.
Although the general appearance of tapeworm
segments from the two Taenia species is quite similar,
trained laboratory personnel can detect distinct differences between the beef and pork tapeworms when
samples are examined under a microscope. Tapeworm
segments and eggs from the fish tapeworm and the
dwarf tapeworm have characteristic appearances that
allow accurate differentiation from the Taenia species
of worms. Other diagnostic procedures may be necessary when cysticercosis is suspected. Blood samples
from an infected individual are collected to look for
GALE ENCYCLOPEDIA OF MEDICINE

Effective treatment of tapeworm infections
involves administering compounds that are toxic to
the adult worm. Many of the early treatments were
also somewhat toxic to the patient, so treatment was
often quite an ordeal. Newer medications are much
more easily tolerated and are highly effective in eliminating the parasite from the body. It is important,
however, to completely eliminate the head and neck
regions of the tapeworm, as the entire worm can regenerate from these parts.
One treatment that has been in use since the early
1960s is niclosamide (Niclocide). This drug is poorly
absorbed from the digestive tract and rapidly kills
tapeworms upon exposure. It has been shown to be
effective against Taenia species and the fish tapeworm,
but treatment of the dwarf tapeworm (Hymenolepis
nana) may require a more prolonged treatment
schedule. Side effects reported with niclosamide are
infrequent and typically mild. When present, side
effects may include nausea, abdominal discomfort,
vomiting, diarrhea, light-headedness, and skin rash.
This medication should be taken in the morning on
an empty stomach. The tablets are chewed thoroughly
and swallowed with water. For young children, the
tablets may be pulverized and mixed with water.
Patients are allowed to eat two hours after treatment.
Recommended dosage is 2 grams for adults and about
half this for children.
Another oral medication that has been shown to be
95% effective in the treatment of tapeworm infections
associated with both Taenia and Diphyllobothrium
latum species is praziquantel (Biltricide). Side effects
reported for praziquantel are mild and appear to be
3625

Tapeworm diseases

the presence of antibodies against the tapeworm larvae. In 2004, researchers isolated an antigen diagnostic for cysticercosis alled GP50. In cases in which
infection of the central nervous system is present,
advanced imaging tests, such as computed tomography
scans and magnetic resonance imaging (MRI), may be
necessary to determine the exact location of the tapeworm larvae within the body.

Tapeworm diseases

KEY TERMS

The head of an adult pork tapeworm. (Custom Medical Stock
Photo. Reproduced by permission.)

short-lived. They include nausea, abdominal pain, itching, sore joints, and muscle pain.
It is recommended that follow-up stool samples be
examined at one month and three months after treatment has been completed. Treatment can be considered successful if no eggs are present in several stool
samples. It should be noted that the tapeworm medications do not kill the tapeworm eggs when they kill
the adult worm, so the potential for infection with eggs
still exists as the dead worm segments are passed.
Proper personal hygiene in individuals receiving treatment will greatly reduce this potential.
Cases of neurocysticercosis, where larvae have
developed in the central nervous system, may also be
treated with praziquantel or albendazole. If the patient
is treated promptly, damage to the central nervous
system will be minimized.
As of late 2003, researchers in developing countries are working on a vaccine for pigs to help control
neurocysticercosis; however, the vaccine is not likely
to be available for several years.

Prognosis
When confined to the intestinal tract, tapeworms
cause minimal damage to their human host. Once the
diagnosis of an intestinal tapeworm infection has been
made, prognosis following treatment with niclosamide
or praziquantel is good. The worms can be eliminated
3626

Cestodiasis—Parasitic infection caused by the presence of adult tapeworms of the class Cestoda
within the intestinal tract. Infection is caused by
accidental consumption of tapeworm larvae.
Cysticercosis—Parasitic infection caused by the
presence of immature tapeworm larvae (cysticerci)
that have developed outside the intestinal tract.
Infection is caused by accidental consumption of
tapeworm eggs.
Diphyllobothriasis—Parasiticinfection causedby the
presence of tapeworms from the Diphyllobothrium
genus, such as the fish tapeworm (Diphyllobothrium
latum).
Hymenolepiasis—Parasitic infection caused by the
presence of tapeworms from the Hymenolepis genus,
such as the dwarf tapeworm (Hymenolepis nana) or
the rodent tapeworm (Hymenolepis diminuta).
Neurocysticercosis—Parasitic infection caused by
the presence of immature tapeworm larvae within
the central nervous system.
Pernicious anemia—Type of anemia caused by a
deficiency in vitamin B12.
Taeniasis—Parasitic infection caused by the presence of tapeworms from the Taenia genus, such
as the pork tapeworm (Taenia solium) or the beef
tapeworm (Taenia saginata).

from the intestines with oral treatment, and there are
usually no residual side effects. Serious problems from
tapeworm infections occur when tapeworm eggs are
consumed and the larvae localize in tissues outside the
digestive tract (cysticercosis). Prompt diagnosis and
treatment of this condition is necessary to prevent
permanent damage to the central nervous system and
other internal organs. In fact, cysticercosis is becoming increasingly recognized as an important cause of
severe neurologic disease in the United States.
Untreated cases of cysticercosis have the rare potential
to be life-threatening; in some cases, liver transplantation has been necessary to save the patient’s life.

Prevention
The best way to prevent infection with tapeworms is
to eliminate the exposure of livestock to the tapeworm
eggs by properly disposing of human feces. The next best
strategy is to thoroughly cook or freeze all meat and fish
before it is eaten to prevent consumption of live
GALE ENCYCLOPEDIA OF MEDICINE

People who raise sheep or horses should have
these animals checked regularly by a veterinarian
and dewormed if necessary.
The Centers for Disease Control and Prevention
(CDC) recommends that people traveling abroad
should wash their hands with soap and water before
handling food; should wash and peel all raw vegetables
and fruits before eating; and should drink only bottled
or boiled water, or carbonated drinks in cans or bottles.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Cestodes (Tapeworms).’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
PERIODICALS

Garcia, H. H., A. E. Gonzalez, C. A. Evans, et al. ‘‘Taenia
solium Cysticercosis.’’ Lancet 362 (August 16, 2003):
547–556.
Richter, J., C. Hatz, and D. Haussinger. ‘‘Ultrasound in
Tropical and Parasitic Diseases.’’ Lancet 362
(September 13, 2003): 900–902.
Schnieder, T. ‘‘Parasitological Risks—From Animal
Husbandry to Food and Humans.’’ [in German]
Deutsche tierartzliche Wochenschrift 110 (August 2003):
326–328.
Sorvillo, Frank J., et al. ‘‘Cysticercosis-related deaths,
California.’’ Emerging Infectious Diseases March 2004:
465–470.
‘‘Taenia Solium Antigen Diagnostic for Cysticercosis
Characterized.’’ Drug Week March 12, 2004: 111.
ORGANIZATIONS

American Veterinary Medical Association (AVMA). 1931
North Meacham Road, Suite 100, Schaumburg, IL
60173-4360. <http://www.avma.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
OTHER

Centers for Disease Control and Prevention (CDC) Fact
Sheet. ‘‘Cysticercosis.’’ <http://www.cdc.gov/ncidod/
dpd/parasites/cysticercosis/
factsht_cysticercosis.htm>.

Geoffrey N. Clark, DVM
Rebecca J. Frey, PhD
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Tardive dyskinesia
Definition
Tardive dyskinesia is a mostly irreversible neurological disorder of involuntary movements caused by
long-term use of antipsychotic or neuroleptic drugs.

Description
Antipsychotic or neuroleptic drugs are powerful
tranquilizers generally prescribed for serious psychiatric disorders, as well as neurological and gastrointestinal disorders. Some common antipsychotics are:
chlorpromazine HCl (Thorazine), thioridazine HCl
(Mellaril), haloperidol (Haldol), perphenazine
(Trilafon), thiothixene (Navane), trifluoperazine HCl
(Stelazine), and fluphenazine HCl (Permitil, Prolixin).
When these drugs are used long term, tardive dyskinesia (TD) can result. About 20 percent of people
taking antipsychotic drugs for more then one year
become affected by TD. The prevalence of TD tends to
be highest among elderly patients and among women.

Causes and symptoms
TD usually appears after years of antipsychotic
drug use, and seems to be related to the total lifetime
dose of medication. The symptoms include the
following:


tongue protrusion



grimacing



rapid eye blinking



lip smacking, pursing, or puckering



rapid movement of the arms or legs



other involuntary movements of the head, face, neck
and tongue muscles

Diagnosis
The diagnosis of TD is suspected upon observation of involuntary movements of the head, neck, face,
and tongue in individuals who have a history of antipsychotic drug prescription.

Treatment
There is no standard treatment for TD. The primary approach is to discontinue or minimize the use of
antipsychotic drugs while attempting to treat some of
the symptoms. The treatment must be individualized to
3627

Tardive dyskinesia

tapeworm larvae in infected samples. Larval cysts in pork
and beef are killed by moderate temperatures of 1508F
(658C) or if frozen for at least 12 hours. Proper cooking of
freshwater fish could also eliminate the possibility of
human infection with the fish tapeworm. Freezing fresh
fish for 24 hours will also kill the larval form.

Tarsorrhaphy

Resources

KEY TERMS
Antipsychotics—Drugs used to treat psychotic conditions such as schizophrenia or psychosis. These
medications are powerful tranquilizers that all have
sedating and calming effects, but their major effect
is to reduce psychotic thinking and behavior.
Neuroleptics—Any of a class of drugs used to treat
psychotic conditions.
Psychosis—A condition where a person’s ability to
recognize reality and cope with everyday life is
severely affected.

BOOKS

Tierney, Lawrence, et al. Current Medical Diagnosis and
Treatment. Los Altos: Lange Medical Publications,
2001.
PERIODICALS

‘‘Risperidone May Lower Incidence of TD.’’ Brown
University geroPsych Report August 2000: 2.
ORGANIZATIONS

National Institute for Mental Health. 6001 Executive Blvd.,
Room 8184, MSC 9663, Bethesda, MD 20892-9663.
<http://www.nimh.nih.gov>.
Tardive Dyskinesia/Tardive Dystonia National
Association. P.O. Box 45732, Seattle, WA 98145-0732.
(206) 522-3166.

Kim A. Sharp, M.Ln.

the patient, because discontinuation of the antipsychotic drug(s) may not be advisable, depending on the
patient’s condition. In some cases, substituting another
drug for the antipsychotic drug may be beneficial.

Prognosis
Once TD appears in full–blown form, it can be
permanent. With careful management, some symptoms
may improve and even disappear with time. In less
severe cases, some patients may recover from TD within
three months of discontinuing the use of antipsychotic
medication. Studies report that at least half of patients
experience remission of major symptoms within 12 to
18 months following discontinuation of antipsychotic
drugs. In some patients, however, decreasing the dose of
the antipsychotic drug actually increases the symptoms
of TD, while increasing the dose sometimes offers a
temporary remission of the symptoms.

Prevention
TD can be prevented by early recognition and
discontinuation of the antipsychotic medication if
this is clinically possible. The use of antipsychotic
drugs should in any case be kept to a minimum in all
patients. Patients should be followed carefully to
determine when the dose of the drug can be tapered
off as the psychiatric condition improves. In all cases,
the benefits of taking the antipsychotic medication
should outweigh the risk of developing TD.
A study has shown that elderly institutionalized
patients with dementia that were treated with risperidone had a low incidence of TD. Although further
study is needed, this study shows that non-conventional
neuroleptic drugs should be considered to avoid the risk
of tardive dyskinesia, particularly in elderly patients.
3628

Tarsorrhaphy
Definition
Tarsorrhaphy is a rare procedure in which the
eyelids are partially sewn together to narrow the
opening.

Purpose
The eye needs the a lid to protect it. It also needs
tears and periodic blinking to cleanse it and keep it
moist. There are many conditions that impair these
functions and threaten the eye, specifically the cornea,
with drying. Until they can be corrected, sewing the
eyelids partially together helps protect the eye.
A partial list of the conditions that can require
tarsorrhaphy includes:


Paralysis or weakness of the eyelids so that they
cannot close or blink adequately. Bell’s palsy is a
nerve condition that weakens the muscles of the
face, including the eyelids. It is usually temporary.
Myasthenia gravis also weakens facial muscles, but it
is usually treatable. A stroke can also weaken eyelids
so they do not close.



Exophthalmos (the eyes sticking out of their sockets)
occurs with Graves’ disease of the thyroid and with
tumors behind the eyes. If the eyes stick out too far,
the lids cannot close over them.



Enophthalmos is a condition in which the eye falls back
into the socket so that the eyelid function is inadequate.
GALE ENCYCLOPEDIA OF MEDICINE

Cornea—The clear part of the front of the eye
through which vision occurs.
Enophthalmos—A condition in which the eye falls
back into the socket and inhibits proper eyelid
function.
Exophthalmos—A condition in which the eyes
stick out of their sockets and inhibit proper eyelid
function.

Tarsorrhaphy carries few risks. If complications
occur, they are usually minor eyelid swelling and
superficial infection.
Resources
BOOKS

Sardegna, Jill Otis, and T. Paul. The Encyclopedia of
Blindness and Vision Impairment. New York: Facts on
File Inc., 1990.

J. Ricker Polsdorfer, MD

Palpebral fissure—Eyelid opening.
Sjögren’s syndrome—A connective tissue disease
that hinders the production of tears and other body
fluids.



Several eye and corneal diseases cause swelling of the
cornea and require temporary added protection until
the condition resolves.



Sjögren’s syndrome reduces tear flow to the point
where it can endanger the cornea.



Dendritic ulcers of the cornea caused by viruses
may need to be covered with the eyelid while they
heal.

Precautions
The use of eye drops and contact lenses to moisten
and protect the eyes must be considered first before
tarsorrhaphy is performed.

Description
Stitches are carefully placed at the corners of the
eyelid opening (called the palpebral fissure) to narrow it. This allows the eye better lubrication and less
exposure to the air. Eyeball motion can then help
bathe the cornea in tears when it rolls up under the
lid. The outpatient procedure is done under local
anesthetic.

Preparation
Tarsorrhaphy is a minor procedure done under
local anesthesia. Special preparation is not necessary.

Aftercare
Eye drops or ointment may still be needed to
preserve the cornea or treat accompanying disease.
GALE ENCYCLOPEDIA OF MEDICINE

Tattoos see Piercing and tattoos

Tay-Sachs disease
Definition
Tay-Sachs disease is a genetic disorder caused by a
missing enzyme that results in the accumulation of a
fatty substance in the nervous system. This results in
disability and death.

Description
Gangliosides are fatty substances necessary for
the proper development of the brain and nerve cells
(nervous system). Under normal conditions, gangliosides are continuously broken down, so that an appropriate balance is maintained. In Tay-Sachs disease, the
enzyme necessary for removing excess gangliosides is
missing. This allows gangliosides to accumulate
throughout the brain, and is responsible for the disability associated with the disease.
Tay-Sachs disease is particularly common among
Jewish people of Eastern European and Russian
(Ashkenazi) origin. About one out of every 3,600
babies born to Ashkenazi Jewish couples will have
the disease. Tay-Sachs is also more common among
certain French-Canadian and Cajun French families.

Causes and symptoms
Tay-Sachs is caused by a defective gene. Genes are
located on chromosomes, and serve to direct specific
development/processes within the body. The genetic
defect in Tay-Sachs disease results in the lack of an
enzyme called hexosaminidase A. Without this
enzyme, gangliosides cannot be degraded. They build
up within the brain, interfering with nerve functioning.
3629

Tay-Sachs disease

Risks

KEY TERMS

Tay-Sachs disease

KEY TERMS
Ganglioside—A fatty (lipid) substance found within
the brain and nerve cells.

Section of brain tissue from patient with Tay-Sachs disease.
(Custom Medical Stock Photo. Reproduced by permission.)

age 20–30. The disease is milder. Speech becomes
slurred. The individual may have difficulty walking
due to weakness, muscle cramps, and decreased coordination of movements. Some individuals develop
mental illness. Many have changes in intellect, hearing, or vision.

Diagnosis
Because Tay-Sachs is a recessive disorder, only people
who receive two defective genes (one from the mother
and one from the father) will actually have the disease.
People who have only one defective gene and one
normal gene are called carriers. They carry the defective gene and thus the possibility of passing the gene
and/or the disease onto their offspring.
When a carrier and a non-carrier have children,
none of their children will actually have Tay-Sachs. It
is likely that 50% of their children will be carriers
themselves. When two carriers have children, their
children have a 25% chance of having normal genes,
a 50% chance of being carriers of the defective gene,
and a 25% chance of having two defective genes. The
two defective genes cause the disease itself.
Classic Tay-Sachs disease strikes infants around
the age of six months. Up until this age, the baby will
appear to be developing normally. When Tay-Sachs
begins to show itself, the baby will stop interacting
with other people and develop a staring gaze.
Normal levels of noise will startle the baby to an
abnormal degree. By about one year of age, the baby
will have very weak, floppy muscles, and may be completely blind. The head will be quite large. Patients also
present with loss of peripheral (side) vision, inability to
breath and swallow, and paralysis as the disorder progresses. Seizures become a problem between ages one
and two, and the baby usually dies by about age four.
A few variations from this classical progression of
Tay-Sachs disease are possible:


Juvenile hexosaminidase A deficiency. Symptoms
appear between ages two and five; the disease progresses more slowly, with death by about 15 years.



Chronic hexosaminidase A deficiency. Symptoms
may begin around age five, or may not occur until

3630

Examination of the eyes of a child with Tay-Sachs
disease will reveal a characteristic cherry-red spot at
the back of the eye (in an area called the retina). Tests
to determine the presence and quantity of hexosaminidase A can be performed on the blood, specially
treated skin cells, or white blood cells. A carrier will
have about half of the normal level of hexosaminidase
A present, while a patient with the disease will have
none.

Treatment
There is no treatment for Tay-Sachs disease.

Prognosis
Sadly, the prognosis for a child with classic TaySachs disease is certain death. Because the chronic
form of Tay-Sachs has been discovered recently, prognosis for this type of the disease is not completely
known.

Prevention
Prevention involves identifying carriers of the disease and providing them with appropriate information
concerning the chance of their offspring having TaySachs disease. When the levels of hexosaminidase A
are half the normal level, a person is a carrier of the
defective gene. Blood tests of carriers reveals reduction
of hexosaminidase A.
When a woman is already pregnant, tests can be
performed on either the cells of the baby (aminocentesis) or the placenta (chorionic villus sampling) to
determine whether the baby will have Tay-Sachs
disease.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

Late Onset Tay-Sachs Foundation. 1303 Paper Mill Road,
Erdenheim, PA 19038. (800)672-2022.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Avenue, White Plains, NY 10605. (888)
663-4637. resourcecenter@modimes.org. <http://
www.modimes.org>.

Laith Farid Gulli, M.D.

TB see Tuberculosis
TCM see Traditional Chinese medicine
TE fistula see Tracheoesophageal fistula

Technetium heart scan
Definition
The technetium heart scan is a noninvasive
nuclear scan that uses a radioactive isotope called
technetium to evaluate blood flow after a heart attack.

Purpose
The technetium heart scan is used to evaluate the
heart after a heart attack. It can confirm that a patient
had a heart attack when the symptoms and pain
usually associated with a heart attack were not present; identify the size and location of the heart attack;
and provide information useful in determining the
patient’s post-heart attack prognosis. The scan is
most useful when the electrocardiogram and cardiac
enzyme studies do not provide definitive results—after
heart surgery, for example, or when chest pain
occurred more than 48 hours before the patient was
examined. It is also used to evaluate the heart before
and after heart surgery.

Precautions
Pregnant women and those who are breastfeeding
should not be exposed to technetium.

Description
The technetium heart scan is a nuclear heart scan,
which means that it involves the use of a radioactive
isotope which targets the heart, and a radionuclide
detector that traces the absorption of the radioactive
isotope. The isotope is injected into a vein and
GALE ENCYCLOPEDIA OF MEDICINE

absorbed by healthy tissue at a known rate during a
certain time period. The radionuclide detector, in this
case a gamma scintillation camera, picks up the
gamma rays emitted by the isotope.
The technetium heart scan uses technetium Tc-99m
stannous pyrophosphate (usually called technetium), a
mildly radioactive isotope that binds to calcium. After a
heart attack, tiny calcium deposits appear on diseased
heart valves and damaged heart tissue. These deposits
appear within 12 hours of the heart attack. They are
generally seen two to three days after the heart attack
and are usually gone within one to two weeks. In some
patients, they can be seen for several months.
After the technetium is injected into a blood vessel
in the arm, it accumulates in heart tissue that has been
damaged, leaving ‘‘hot spots’’ that can be detected by
the scintillation camera. The technetium heart scan
provides better image quality than commonly used
radioactive agents such as thallium, because it has a
shorter half-life and can thus be given in larger doses.
During the test, the patient lies motionless on the
test table. Electrocardiogram electrodes are placed on
the patient’s body for continuous monitoring during
the test. The test table is rotated so that different views
of the heart can be scanned. The camera, which looks
like an x-ray machine and is suspended above the
table, moves back and forth over the patient. It displays a series of images of technetium’s movement
through the heart and records them on a computer
for later analysis.
The test is usually performed at least 12 hours
after a suspected heart attack, but it can also be done
during triage of a patient who goes to a hospital emergency room with chest pain but does not appear to
have had a heart attack. Recent clinical studies
demonstrate that technetium heart scans are very
accurate in detecting heart attacks while the patient
is experiencing chest pain. They are far more accurate
than electrocardiogram findings.
The technetium heart scan is usually performed in
a hospital’s nuclear medicine department but it can be
done at the patient’s bedside during a heart attack if
the equipment is available. The scan is done two to
three hours after the technetium is injected. Scans are
usually done with the patient in several positions, with
each scan taking 10 minutes. The entire test takes
about 30 minutes to an hour. The scan is usually
repeated over several weeks to determine if any further
damage has been done to the heart. The test is also
called technetium 99m pyrophosphate scintigraphy,
hot-spot myocardial imaging, infarct avid imaging,
or myocardial infarction scan.
3631

Technetium heart scan

Resources

Teeth whitening

KEY TERMS

Teeth whitening

Electrocardiogram—A test in which electronic
sensors called electrodes are placed on the body
to record the heart’s electrical activities.
Noninvasive—A procedure that does not penetrate
the body.
Radioactive isotope—One of two or more atoms
with the same number of protons but a different
number of neutrons with a nuclear composition.
In nuclear scanning, radioactive isotopes are used
as a diagnostic agent.
Technetium—A radioactive isotope frequently used
in radionuclide scanning of the heart and other
organs. It is produced during nuclear fission reactions.

The technetium heart scan is not dangerous. The
technetium is completely gone from the body within a
few days of the test. The scan itself exposes the patient
to about the same amount of radiation as a chest x ray.
The patient can resume normal activities immediately
after the test.

Preparation
Two to three hours before the scan, technetium is
injected into a vein in the patient’s forearm.

Normal results
If the technetium heart scan is normal, no technetium will show up in the heart.

Abnormal results
In an abnormal technetium heart scan, hot spots
reveal damage to the heart. The larger the hot spots,
the poorer the patient’s prognosis.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
Texas Heart Institute. Heart Information Service. P.O. Box
20345, Houston, TX 77225-0345. <http://
www.tmc.edu/thi>.

Lori De Milto

TEE see Transesophageal echocardiography
3632

Definition
Teeth whitening is the process of using bleach or
other materials to make teeth look whiter. The materials remove stains or other discoloration from the tooth
surface.

Purpose
Teeth whitening is a cosmetic treatment done to
improve the appearance of teeth. Teeth are whitened
to remove the effects of coffee, cigarettes, and other
substances that permanently stain or discolor teeth.
Medications such as antibiotics like tetracycline may
discolor teeth. Fluorosis, a condition caused by
absorbing too much fluoride, could affect tooth
color. Furthermore, aging also causes teeth to loose
their bright color.

Precautions
Teeth whitening is not safe or effective for everyone, so a person should have a dental exam before
starting treatment. The dentist can advise the patient
about the most appropriate procedure. The oral
health professional will also discuss the expected
results of treatment. Patients may expect yellow or
gray teeth to be replaced with a bright, white color.
However, whitening may not work well on some stain
colors.
The importance of a check-up
Whitening may not be recommended for people
with gum disease, receding gums, or sensitive teeth.
The dentist may advise against certain treatments if
the enamel is worn. Enamel is the outer layer of the
tooth. There is no enamel on an exposed tooth root, so
the root cannot be whitened.
In addition, cavities must be filled before treatment begins. Otherwise, the patient could experience
additional mouth sensitivity when treatment material
comes into contact with decay or the tooth interior.
When whitening is not recommended
Women who are pregnant and nursing should
avoid any whitening treatment except for toothpaste.
Oral health care professionals advise that other treatments could contain levels of peroxide that are potentially dangerous to the child. Although no connections
have been made between these treatments and harm to
GALE ENCYCLOPEDIA OF MEDICINE

Teenagers should not have their teeth bleached
until they are between 14 and 16 years old. In a
younger child, the nerve of the tooth called the pulp
chamber has not fully developed. Whitening at this
point could irritate the pulp and cause sensitivity.
People who are allergic to peroxide should not be
treated with this whitening agent.
Cautions about tooth color
Treatments such as bleaching are most effective
on yellowish stains, according to the American Dental
Association (ADA). Teeth with brown stains may not
bleach as well, and the treatment is even less effective
on gray-stained teeth.
Furthermore, bleaching will not change the color
of tooth-colored fillings, dentures, crowns, porcelain
restorations, bonding, or other material used to
restore or replace a tooth. If bleaching is done, the
newly whitened teeth will stand out in contrast to
fillings or other modifications.

Description
Teeth are whitened by the use of bleach or other
material. The treatment may be done in the dental
office, at home with guidance from a dentist, or at
home with the use of over-the-counter products.
Tools for self-treatment include bleaching trays, gels
or strips that are applied to the teeth, and toothpaste.
Whitening treatments are cosmetic procedures,
and are usually not covered by dental insurance.
Products used by oral health professionals such
and those sold over the counter may have the ADA
Seal of Acceptance. This endorsement indicates that
products carrying the seal have met the American
Dental Association’s criteria for safety and effectiveness. Those standards are based on the patient following directions when the product is used.
The ADA evaluation program is voluntary. That
means manufacturers are not required to submit products for review. As a result, the lack of a seal may not
indicate that the product is unsafe. However, products
on the Accepted list have the ADA endorsement, and
the association may take positions on certain unevaluated procedures such as laser treatment.
Dental office treatment
The whitening treatment provided by dentists is
known as chairside bleaching, in-office bleaching, or
GALE ENCYCLOPEDIA OF MEDICINE

power bleaching. The dentist first protects the
patient’s gums and tissue by applying a protective gel
or a rubber shield. The dentist than applies a whitening solution on the teeth.
The whitening solution contains hydrogen peroxide, which is a bleaching agent that could change the
tooth color. The bleach is used to remove surface
(extrinsic)
and
deeper
(intrinsic)
stains.
Professionally applied whiteners, those solutions
used by dentists, usually contain hydrogen peroxide.
This bleaching agent comes in concentrations ranging
from 15% to 35%. As of March of 2005, all solutions
with the ADA Seal had a 35% concentration of hydrogen peroxide.
After the gel is applied, a light may be shined on
the teeth to accelerate the whitening agent. Some
agents are enhanced by lasers. However, no treatments
requiring lasers were on the ADA list of accepted
products as of March 2005. Although lasers may be
safe, the association had not seen published, peerreviewed data on the safety and effectiveness of laser
whitening.
Chairside bleaching treatment may last from
thirty minutes to an hour, according to the ADA. In
addition, patients may need to return for additional
treatments. The cost of treatment for the whole mouth
can cost from $500 to $1,000. Factors affecting cost
include the patient’s location and the number of treatments needed. At the high end of the range is laser
treatment, which could cost $1,000 or more.
Dentist-supervised treatment
Supervised treatment combines visits to the dentist with treatment at home. The procedure is also
called tray bleaching or nightguard bleaching because
the patient wears a tray on the teeth that protects the
gums from the whitening solution.
For this treatment, the dentist takes an impression
of the patient’s teeth and makes a mouthpiece tray, or
mouthguard, that will fit over the teeth. The dentist
dispenses a whitening gel that the patient will place in
the customized mouthguard.
The gel usually contains carbamide peroxide,
which comes in concentrations of 10%, 16%, and
22%. Products with the ADA Seal have a 10% concentration. That amount is the equivalent of an
approximately 3% concentration of hydrogen peroxide. The ADA endorsement applies only to home systems dispensed by dentists. The association’s Seal
reflects the importance of consulting with a dentist
before undergoing treatment at home, according to
the ADA.
3633

Teeth whitening

the child’s health, mothers are urged to take preventive
action and delay whitening treatment.

Teeth whitening

The dentist will set up a schedule for wearing the
mouthguard. Wearing times vary by product. A
patient may we ar the piece overnight for one to two
weeks. For other systems, the patient wears the
mouthguard for a set amount of time twice a day.
This treatment usually lasts two weeks.
During supervised treatment, the dentist generally
schedules appointments to monitor the patient’s progress. In addition to checking the whitening process,
the dentist may examine the fit of the mouthguard and
look for signs of gum irritation.
Supervised home bleaching of the whole mouth
costs from $300 to $600.
Over-the-counter (OTC) products
In-home treatments that can be purchased overthe-counter include products that use bleach in
mouthguard trays as well as strips and gels. The
bleaching agent is usually carbamide peroxide, which
is not as strong as the hydrogen peroxide found in
solutions that are used in chairside bleaching and
supervised home treatment.
OTC treatments range in price from $20 to $150.
Treatment lasts 14 days on average. Another treatment is the use of whitening toothpaste, a product
that does not contain bleach.
TRAY TREATMENT. Mouthguard treatment kits can

be bought in stores and over the Internet. The tray kits
involve the use of a mouthguard and gel. While similar
to dentist-supervised home treatment, the patient does
not use a customized tray specifically for her or his
mouth. Some kits have mouthguards that patients can
mold to their teeth. However, the patient relies on the
generic instructions provided by the manufacturer.
GELS AND WHITENING STRIPS. Gels are applied

KEY TERMS
Enamel—The hard, white, outer layer of the tooth.
Fluoride—A compound believed to combat cavities in teeth.
Peroxide—A bleaching agent that is a compound
consisting of two atoms of oxygen connected by a
single bond.

dentist can review the patient’s oral health history and
discuss the appropriate treatment. If necessary, the
dentist will fill cavities.

Aftercare
During supervised at-home treatment, the dentist
may schedule appointments to check on the progress
of whitening, side effects, and the tray fit.
After treatment is completed, people need to be
aware that smoking will cause teeth to discolor.
Beverages with caffeine should be consumed with a
straw to reduce the effects of staining. Another preventive action is brushing the teeth after drinking or
eating foods that cause stains.

Risks
Teeth-whitening may cause sensitivity to hot and
cold food and beverages. This is a temporary side
effect that usually ends when treatment is completed.
Some patients also experience gum irritation if the tray
does not fit properly.

Normal results

directly to the teeth. Whitening strips are thin, clear
strips coated with a peroxide-based gel. The strips are
applied to the teeth and worn for 30 minutes twice a
day. Treatment time varies by product and generally
lasts from five to 14 days.

Dentists use a stronger bleaching agent than that
found in commercial products, so in-office whitening
treatment produces a more dramatic effect on teeth
with yellow stains. Over-the-counter products with
bleach provide some change in the tooth color, and
whitening toothpaste works only on surface stains.

WHITENING TOOTHPASTES. Whitening toothpastes do not contain bleach. Instead mild abrasives
remove surface stains, but do not change tooth color.
Products with the ADA Seal contain special chemicals
or polishing agents that remove stains. A tube of
whitening toothpaste costs about $5.

Bleaching does not leave teeth permanently white.
Whitening can last from six months to a year.
Sometimes teeth stay white even longer. However,
smoking or consumption of food and beverages that
stain can cause discoloration within one month.
Resources

Preparation
The ADA advises people to consult with a dentist
before beginning any teeth whitening treatment. The
3634

PERIODICALS

Caruana, Claudia M. ‘‘The Smiles Have It!’’ Vegetarian
Times, February 2003, 35-39.
GALE ENCYCLOPEDIA OF MEDICINE

the body may be affected. The disease seems to
target arteries containing elastic tissue. Veins are
rarely affected. Temporal arteritis is a type of
vasculitis.

ORGANIZATION

Academy of General Dentistry. 211 East Chicago Avenue,
Suite 900, Chicago, IL 60611-1999. 888-AGD-DENT
(888-243-3368). <http://www.agd.org>.
American Dental Association. 211 East Chicago Avenue,
Chicago, IL 60611-2678. 312-440-2500. <http://
www.ada.org>.
American Dental Hygienists’ Association. 444 North
Michigan Avenue, Suite 3400, Chicago, IL 60611. 312440-8927.<http://www.adha.org>.
OTHER

‘‘Teeth Whitening: Is it for you?’’ Academy of General
Dentistry. December 20, 2004 [cited March 21, 2005].
<http://www.agd.org/media/2004/dec/
whitening.asp>.
‘‘Tooth Whitening Systems.’’ American Dental Hygienists’
Association 2005 [cited March 21, 2005]. <http://
www.adha.org/oralhealth/whitening.htm>.
‘‘Tooth Whitening Treatments.’’ American Dental
Association 2005 [cited March 21, 2005]. <http://
www.ada.org/public/topics/whitening.asp>.

Liz Swain

Template bleeding time see Bleeding time

Description
Temporal arteritis almost always occurs in
people over 50, and it becomes more common as
people age. About 20 out of 100,000 people over
the age of 50 suffer from temporal arteritis.
Women are affected twice as often as men. Some
authorities say that temporal arteritis is more common in Caucasians (especially Scandinavians) than
in people of other races. Close relatives of patients
with temporal arteritis may be more likely than
others to get the disease.
Patients with temporal arteritis are diagnosed
and overlap with a broader disorder called giant cell
arteritis. This can affect parts of the body in addition
to the scalp, eyes, and jaw. Sometimes the disease can
cause restricted circulation to both arms or both legs,
producing pain in the affected limbs. With other
blood vessels involved, patients with advanced
forms of the disease may experience strokes or transient ischemic attacks (TIA). These result in brief
episodes of pain caused by decreased blood flow.
Even heart attacks are occasionally caused by giant
cell arteritis.

Causes and symptoms

Temporal arteritis
Definition
The term temporal arteritis literally means
‘‘inflammation of the temporal arteries.’’ As implied
by the name, these blood vessels run along the temples after they branch off from the carotid artery in
the neck. They provide the blood supply to portions
of the scalp, jaw muscles, and salivary glands.
Inflammation of these arteries, probably resulting
from an abnormal immune reaction, disrupts this
blood supply, resulting in a variety of symptoms.
They can range from relatively minor jaw pain or
headache to major symptoms, including temporary
or permanent blindness.
Temporal arteritis is also called giant cell arteritis or cranial arteritis. It is a rheumatic disease
that affects large and medium-sized arteries
throughout the body and can occur in a variety
of patients. Although the temporal arteries are
most commonly affected, other arteries throughout
GALE ENCYCLOPEDIA OF MEDICINE

This disease is one of a group of diseases in which
the linings of large- or medium-sized blood vessels
become inflamed. The elastic layer of these vessels is
attacked by ‘‘giant’’ cells and chemicals produced by
the immune system. This reaction reduces blood flow
through the blood vessels, and the limited blood supply causes the symptoms.
The disease usually begins with ‘‘flu-like’’ symptoms, including a mild fever (100–1018F), general
body discomfort, and a persistent, dull headache. The
scalp may be tender to the touch over the affected
blood vessels. Jaw muscles sometimes become painful
when the patient chews.
As the disease progresses, more severe symptoms occur. These include blurred vision or temporary blindness that typically lasts ten minutes or
less. Eventually, permanent loss of vision can
occur. Transient ischemic attacks, strokes, and
heart attacks may occur when the disease is far
advanced.
3635

Temporal arteritis

Foley, Denise; Poust, Jenny. ‘‘Home Tooth-Whitening
Kits.’’ Prevention,February 2004, 160 (4 pages)[cited
March 21, 2005]. <http://search.epnet.com/login.
aspx?direct=true&db=hxh&an=11891865>.

Temporal arteritis

Diagnosis
Doctors from a number of specialties develop
experience in diagnosing and treating temporal arteritis.
These include internists, who treat a broad range of
diseases; rheumatologists, who focus on rheumatic diseases; geriatricians, who treat older people; ophthalmologists, who treat eye and vision disorders; neurologists,
who treat headaches and problems of the optic nerve;
and vascular surgeons, who treat blood vessel problems.
The doctor will generally take a medical history
first. The patient can help the doctor tremendously by
reviewing all symptoms–both major and minor–from
the last two or three months. If possible, the patient
should ask family or close friends for help in recalling
his/her ailments from recent months. Then the doctor
will conduct a complete physical examination. Often, he
or she will detect a tender, swollen artery on the scalp.
The doctor will order blood tests as well. A standard and inexpensive test called the erythrocyte sedimentation rate (ESR or ‘‘sed’’ rate) is particularly
helpful. Results from this test, which measures inflammation in the body, will almost always be higher than
normal. Tests of the red blood cells may show mild
anemia. Sometimes blood tests for liver function will
also be abnormal.
The definitive diagnostic test is a temporal artery
biopsy. A doctor will make one or more tiny incisions
under local anesthesia to remove samples of the suspect artery. Under the microscope, a pathologist
usually can identify the typical damage caused by
temporal arteritis.

Treatment
The mainstay of treatment is a course of corticosteroids (steroid hormones that have an antiinflammatory effect), usually prednisone. The initial
prescription involves a fairly high dose of steroids
(40–60 mg/day) which is gradually tapered down to
a maintenance dose. Because of the high incidence of
blindness in untreated cases, steroid therapy should
be started immediately rather than waiting for biopsy
results. Patients typically take this maintenance dose
for periods of one to three years. Sometimes nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for muscle aches or headaches, especially
while steroid doses are being reduced.

Prognosis
The outlook for most patients with temporal
arteritis is good, especially if the disorder is
3636

KEY TERMS
Anemia—Lower than normal level of red blood
cells, or of the oxygen-carrying chemical
hemoglobin.
Biopsy—Removal and examination of a sample
tissue from the body for diagnostic purposes.
Corticosteroids—A group of hormones, produced
naturally by the adrenal gland and other organs.
They are used to treat a wide variety of disorders,
including many rheumatic disorders.
Erythrocyte sedimentation rate—The speed at
which red blood cells sink in a tube of freshly
drawn blood, which is a rough measure of clotting
disorders or inflammation.
Prednisone—A corticosteroid often used to treat
inflammation.
Rheumatic disease—A type of disease involving
inflammation of muscles, joints, and other tissues.
Transient ischemic attack—A brief experience of
stroke-like symptoms (for instance, numbness,
paralysis, problems in speaking or understanding
speech) that go away within hours, with no permanent damage. Also known as TIA.
Vasculitis—An inflammation of the blood vessels.

diagnosed early. Symptoms often diminish within a
month once patients begin to take steroids. Although
physicians do not talk about a ‘‘cure’’ for temporal
arteritis, symptoms typically do not return after a full
course of steroid treatment. Unfortunately, if the
diagnosis is made late in the disease, lost vision may
not return.

Prevention
There is no medically proven approach to prevention. The best way to prevent severe, permanent
damage is to obtain expert medical advice if the
patient or the family physician suspects this
problem.
Resources
ORGANIZATIONS

National Headache Foundation. 428 W. St. James Place,
Chicago, IL 60614. (800) 843-2256. <http://
www.headaches.org>.

Richard H. Lampert
GALE ENCYCLOPEDIA OF MEDICINE

Internal derangement. Internal derangement is a condition in which the cartilage disk lies in front of its
proper position. In most cases of internal derangement, the disc moves in and out of its correct location,
making a clicking or popping noise as it moves. In a
few cases, the disc is permanently out of position, and
the patient’s range of motion in the jaw is limited.



Hypermobility. Hypermobility is a condition in
which the ligaments that hold the jaw in place are
too loose and the jaw tends to slip out of its socket.



Birth abnormalities. These are the least frequent cause
of TMJ but do occur in a minority of patients. In some
cases, the top of the jawbone is too small; in others,
the top of the jawbone outgrows the lower part.

Definition
Temporomandibular joint disorder (TMJ) is the
name given to a group of symptoms that cause pain in
the head, face, and jaw. The symptoms include headaches, soreness in the chewing muscles, and clicking or
stiffness of the joints. They often have psychological as
well as physical causes.

Description
TMJ disorder, which is also sometimes called
TMJ syndrome, results from pressure on the facial
nerves due to muscle tension or abnormalities of the
bones in the area of the hinge joint between the lower
jaw and the temporal bone. This hinge joint is called
the temporomandibular joint. There are two temporomandibular joints, one on each side of the skull just
in front of the ear. The name of the joint comes from
the two bones that make it up. The temporal bone is
the name of the section of the skull bones where the
jaw bone (the mandible) is connected. The jaw bone is
held in place by a combination of ligaments, tendons,
and muscles. The temporomandibular joint also contains a piece of cartilage called a disc, which keeps the
temporal bone and the jaw bone from rubbing against
each other. The jaw pivots at the joint area in front of
the ear. The pivoting motion of the jaw is complicated
because it can move downward and from side to side
as well as forward. Anything that causes a change in
shape or functioning of the temporomandibular joint
will cause pain and other symptoms.

Causes and symptoms
Causes
TMJ syndrome has several possible physical
causes:


Muscle tension. Muscle tightness in the temporomandibular joint usually results from overuse of
muscles. This overuse in turn is often associated
with psychological stress and clenching or grinding
of the teeth (bruxism).



Injury. A direct blow to the jaw or the side of the
head can result in bone fracture, soft tissue bruising,
or a dislocation of the temporomandibular joint
itself.



Arthritis. Both osteoarthritis and rheumatoid arthritis
can cause TMJ.

GALE ENCYCLOPEDIA OF MEDICINE

Symptoms
The symptoms of TMJ depend in part on its cause.
The most common symptoms are facial pain in front of
the ears; headaches; sore jaw muscles; a clicking sound
when chewing; a grating sensation when opening and
closing the mouth; and temporary locking of the jaw.
Some patients also report a sensation of buzzing or
ringing in the ears. Usually, the temporomandibular
joint itself is not painful. Most cases of TMJ are seen
in women between 20-50 years of age.

Diagnosis
Dental examination and patient history
TMJ disorders are most frequently diagnosed by
dentists. The dentist can often diagnose TMJ based on
physical examination of the patient’s face and jaw. The
examination might include pressing on (palpating) the
jaw muscles for soreness or asking the patient to open
and close the jaw in order to check for misalignment of
the teeth in the upper and lower jaw. This condition is
called malocclusion. The dentist might also gently move
the patient’s jaw in order to check for loose ligaments.
Imaging studies
Imaging studies are not usually necessary to diagnose TMJ. In most cases, x rays and MRI scans of
the temporomandibular joint will be normal.
Consequently, these two tests are not commonly
used to diagnose TMJ. If the dentist suspects that the
patient has internal derangement of the disc, he or she
can use a technique called arthrography to make
the diagnosis. In an arthrogram, a special dye is
injected into the joint, which is then x-rayed.
Arthrography can be used to evaluate the movement
of the jaw and the disc as well as size and shape, and to
evaluate the effectiveness of treatment for TMJ.
3637

Temporomandibular joint disorders



Temporomandibular joint
disorders

Tendinitis

Physical therapy and mechanical devices

KEY TERMS
Arthrography—An imaging technique that is
sometimes used to evaluate TMJ associated with
internal derangement.
Bruxism—Habitual clenching and grinding of the
teeth, especially during sleep.
Electromyographic biofeedback—A method for
relieving jaw tightness by monitoring the patient’s
attempts to relax the muscle while the patient
watches a gauge. The patient gradually learns to
control the degree of muscle relaxation.
Internal derangement—A condition in which the
cartilage disc in the temporomandibular joint lies
in front of its proper position.
Malocclusion—The misalignment of opposing
teeth in the upper and lower jaws.
Mandible—The medical name for the lower jaw.
Osteoarthritis—A type of arthritis marked by
chronic degeneration of the cartilage of the joints,
leading to pain and sometimes loss of function.
Rheumatoid arthritis—A chronic autoimmune disorder marked by inflammation and deformity of the
affected joints.
Temporal bones—The compound bones that form
the left and right sides of the skull.
Transcutaneous electrical nerve stimulation—A
method for relieving the muscle pain of TMJ by
stimulating nerve endings that do not transmit
pain. It is thought that this stimulation blocks
impulses from nerve endings that do transmit pain.

Patients who have difficulty with bruxism are
usually treated with splints. A plastic splint called a
nightguard is given to the patient to place over the
teeth before going to bed. Splints can also be used to
treat some cases of internal derangement by holding
the jaw forward and keeping the disc in place until the
ligaments tighten. The splint is adjusted over a period
of two to four months.
TMJ can also be treated with ultrasound, electromyographic biofeedback, stretching exercises,
transcutaneous electrical nerve stimulation, stress
management techniques, or friction massage.
Surgery
Surgery is ordinarily used only to treat TMJ
caused by birth deformities or certain forms of internal
derangement caused by misshapen discs.

Prognosis
The prognosis for recovery from TMJ is excellent for
almost all patients. Most patients do not need any form of
long-term treatment. Surgical procedures to treat TMJ
are quite successful. In the case of patients with TMJ
caused by arthritis or infectious diseases, the progression
of the arthritis or the success of eliminating infectious
agents determines whether TMJ can be eliminated.
Resources
BOOKS

Berktow, Robert, et al., editor. ‘‘Disorders of the
Temporomandibular Joint.’’ In Merck Manual of
Medical Information: Home Edition. Whitehouse
Station, NJ: Merck Research Laboratories, 1997.

John T. Lohr, PhD

Treatment
In many cases, the cause of pain in the TMJ
area is temporary and disappears without treatment. About 80% of patients with TMJ will
improve in six months without medications or physical treatments.

TEN see Toxic epidermal necrolysis

Tendinitis
Medications
Patients with TMJ can be given muscle relaxants if
their symptoms are related to muscle tension. Some
patients may be given aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) for minor discomfort.
If the TMJ is related to rheumatoid arthritis, it may be
treated with corticosteroids, methotrexate (MTX,
Rheumatrex) or gold sodium (Myochrysine).
3638

Definition
Tendinitis is the inflammation of a tendon, a
tough rope-like tissue that connects muscle to bone.

Description
Tendinitis usually occurs in individuals in middle
or old age because it is often the result of overuse over
GALE ENCYCLOPEDIA OF MEDICINE

tendons that commonly become inflamed include:

KEY TERMS
Biceps—The muscle in the front of the upper arm.



tendons of the hand



tendons of the upper arm that effect the shoulder

Infraspinatus—A muscle at the middle of the
shoulder blade.



achilles tendon and the tendon that runs across the
top of the foot

Supraspinatus—A muscle at the top of the shoulder
blade.

Causes and symptoms
Sudden stretching or repeated overuse injures the
connection between the tendon and its bone or muscle. The injury is largely mechanical, but when it
appears, the body tries to heal it by initiating inflammation. Inflammation increases the blood supply,
bringing nutrients to the damaged tissues along with
immunogenic agents to combat infection. The result
is swelling, tenderness, pain, heat, and redness if the
inflammation is close to the skin.

Diagnosis
Some tendon injuries are superficial and easy to
identify. These include ‘‘tennis elbow’’ (extensor tendinitis) over the outside of the elbow, and Achilles’ tendinitis
just above the heel of the foot. There are several tendons
in the shoulder that can be overused or stretched, and
usually a shoulder will have more than one injury at a
time. Tendinitis in the biceps, the infraspinatus, or the
supraspinatus tendon may accompany a tear of the
shoulder ligaments or an impingement of one bone or
another. Careful pressure testing and movement of the
parts is all that is necessary to identify the tendinitis.

Treatment
Rest, ice, compression, and elevation (RICE) will
treat the acute condition. The best way to apply ice is
in a bag with water. The water applies the cold directly
to the skin. Chemical ice packs can get too cold and
cause frostbite. Compression using an elastic wrap
minimizes swelling and bleeding in an acute sprain.
Splinting may help rest the limb. Pain and anti-inflammatory medications (aspirin, naproxen, ibuprofen)
will help. Sometimes the inflammation lingers and
requires additional treatment. Injections of cortisone-like medicine often relieve chronic tendinitis,
but should be reserved for resistant cases since cortisone can occasionally cause problems of its own.
If tendinitis is persistent and unresponsive to nonsurgical treatment, a surgery to remove the afflicted
portion of tendon can be performed. Surgery is also
GALE ENCYCLOPEDIA OF MEDICINE

conducted to remove calcium buildup that comes with
persistent tendinitis.

Alternative treatment
An osteopathic soft-tissue treatment on the tendon may relieve pain and increase mobility. Increasing
intake of antioxidant-rich foods and lowering intake
of animal fats may help reduce the inflammation.
Acupuncture has also been used to combat tendinitis.
Hydrotherapies, such as whirlpool baths, help relax
the surrounding muscles.

Prognosis
Generally, tendinitis will heal if the provoking
activity is stopped.

Prevention
If given enough time, tendons will strengthen to
meet the demands placed on them. They grow slowly
because of their poor blood supply, so adequate time is
required for good conditioning.
Resources
BOOKS

Gilliland, Bruce C. ‘‘Relapsing Polychondritis and Other
Arthritides.’’ In Harrison’s Principles of Internal
Medicine, edited by Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

Tennis elbow
Definition
Tennis elbow is an inflammation of several structures of the elbow. These include muscles, tendons,
3639

Tennis elbow

a long period of time. Tendinitis does occur in younger
patients as a result of acute overuse.

Tennis elbow

bursa, periosteum, and epicondyle (bony projections
on the outside and inside of the elbow, where muscles
of the forearm attach to the bone of the upper arm).

Description
The classic tennis elbow is caused by repeated
forceful contractions of wrist muscles located on the
outer forearm. The stress, created at a common muscle origin, causes microscopic tears leading to inflammation. This is a relatively small surface area located
at the outer portion of the elbow (the lateral epicondyle). Medial tennis elbow, or medial epicondylitis, is
caused by forceful, repetitive contractions from muscles located on the inside of the forearm. All of the
forearm muscles are involved in tennis serves, when
combined motions of the elbow and wrist are
employed. This overuse injury is common between
ages 20 and 40.
People at risk for tennis elbow are those in occupations that require strenuous or repetitive forearm
movement. Such jobs include mechanics or carpentry. Sport activities that require individuals to twist
the hand, wrist, and forearm, such as tennis, throwing a ball, bowling, golfing, and skiing, can cause
tennis elbow. Individuals in poor physical condition
who are exposed to repetitive wrist and forearm
movements for long periods of time may be prone
to tennis elbow. This condition is also called epicondylitis, lateral epicondylitis, medial epicondylitis, or
golfer’s elbow, where pain is present at the inside
epicondyle.

Causes and symptoms
Tennis elbow pain originates from a partial tear of
the tendon and the attached covering of the bone. It is
caused by chronic stress on tissues attaching forearm
muscles known as extensor muscles to the elbow area.
Individuals experiencing tennis elbow may complain
of pain and tenderness over either of the two epicondyles. This pain increases with gripping or rotation of
the wrist and forearm. If the condition becomes longstanding and chronic, a decrease in grip strength can
develop.

Diagnosis
Diagnosis of tennis elbow includes the individual
observation and recall of symptoms, a thorough medical history, and physical examination by a physician.
Diagnostic testing is usually not necessary unless there
may be evidence of nerve involvement from underlying causes. X rays are usually always negative because
3640

the condition is primarily soft tissue in nature, in contrast to a disorder of the bones. However, magnetic
resonance imaging (MRI) has been shown to be helpful
in diagnosing cases of early tennis elbow because it can
detect evidence of swelling and tissue tears in the common extensor muscle group.

Treatment
Conservative
Heat or ice is helpful in relieving tennis elbow
pain. Once acute symptoms have subsided, heat treatments are used to increase blood circulation and promote healing. The physician may recommend physical
therapy to apply diathermy or ultrasound to the
inflamed site. These are two common modalities used
to increase the temperature of the tissues in order to
address both pain and inflammation. Occasionally, a
tennis elbow splint or taping may be useful to help
decrease stress on the elbow throughout daily activities. Exercises become very important to improve
flexibility to all forearm muscles, and will aid in
decreasing muscle and tendon tightness that has been
creating excessive pull at the common attachment of
the epicondyle.
The physician may also prescribe nonsteroidal
anti-inflammatory drugs (NSAIDS) to reduce inflammation and pain. Injections of cortisone or anesthetics
are often used if physical therapy is ineffective.
Cortisone reduces inflammation, and anesthetics temporarily relieve pain. Physicians are cautious regarding an excessive number of injections as they have been
found to weaken the tendon’s integrity. In addition, a
significant number of patients experience a temporary
increase in pain following corticosteroid injections.
A newer method of treatment for tennis elbow is
shock wave therapy, in which pulses of high-pressure
sound are directed at the injured part of the tendon.
The ‘‘shock’’ refers to the high pressure, which breaks
down scar tissue and stimulates the regrowth of blood
vessels in healthy tissue. Shock wave therapy sessions
take about 20 minutes and have been reported to have
a success rate of 80%. Shock wave therapy has very
few side effects; one group of German physicians
found that temporary reddening of the skin or small
bruises were the most commonly reported side effects.
Botulinum toxin, or Botox, is also being tried as a
treatment for tennis elbow as of late 2003. Although
further research needs to be done, Botox appears to
relieve pain in chronic tennis elbow by relaxing muscles that have gone into spasm from prolonged
inflammation.
GALE ENCYCLOPEDIA OF MEDICINE

Tennis elbow

Small tear in
tendon tissue

Epicondylitis
The classic tennis elbow is caused by repeated forceful contractions of wrist muscles located on the outer forearm. The stress
created at a common muscle origin causes microscopic tears leading to inflammation. Persons who are most at risk of
developing tennis elbow are those whose occupations requires strenuous or repetitive forearm movement. (Illustration by
Electronic Illustrators Group.)

Surgery
If conservative methods of treatment fail, surgical
release of the tendon at the epicondyle may be a necessary form of treatment. However, surgical intervention is relatively rare.

Alternative treatment
Massage therapy has been found to be beneficial if
symptoms are mild. Massage techniques are based
primarily on increasing circulation to promote efficient reduction of inflammation. Manipulation, acupuncture, and acupressure have been used as well.
Contrast hydrotherapy (alternating hot and cold
water or compresses, three minutes hot, 30 seconds
cold, repeated three times, always ending with cold)
applied to the elbow can help bring nutrient-rich blood
GALE ENCYCLOPEDIA OF MEDICINE

to the joint and carry away waste products. Botanical
medicine and homeopathy may also be effective therapies for tennis elbow. For example, cayenne (Capsicum
frutescens) ointment or prickly ash (Zanthoxylum
americanum) oil applied topically may help to increase
blood flow to the affected area and speed healing.

Prognosis
Tennis elbow is usually curable; however, if symptoms become chronic, it is not uncommon for treatment to continue for three to six months.

Prevention
Until symptoms of pain and inflammation subside, activities requiring repetitive wrist and forearm
3641

Tensilon test

KEY TERMS
Epicondyle—A projection on the surface of a bone;
often an area for muscle and tendon attachment.
Epicondylitis—A painful and sometimes disabling
inflammation of the muscle and surrounding tissues
of the elbow caused by repeated stress and strain on
the forearm near the lateral epicondyle of the
humerus (arm bone).
Extensor muscles—A group of muscles in the forearm that serve to lift or extend the wrist and hand.
Tennis elbow results from overuse and inflammation of the tendons that attach these muscles to the
outside of the elbow.
Periosteum—A fibrous vascular membrane that
covers bones.
Shock wave therapy—A method of treating tennis
elbow and other musculoskeletal injuries that
involves directing bursts of high-pressure sound
waves at the affected area.

Resonance Imaging.’’ Occupational Medicine (London)
53 (August 2003): 309–312.
Melikyan, E. Y., E. Shahin, J. Miles, and L. C. Bainbridge.
‘‘Extracorporeal Shock-Wave Treatment for Tennis
Elbow. A Randomised Double-Blind Study.’’ Journal
of Bone and Joint Surgery, British Volume 85 (August
2003): 852–855.
Rompe, J. D., M. Buch, L. Gerdesmeyer, et al.
‘‘Musculoskeletal Shock Wave Therapy— Current
Database of Clinical Research.’’ [in German] Zeitschrift
Orthopädische Ihre Grenzgebiet 140 (May-June 2002):
267-274.
Smith, A. M., J. A. Castle, and D. S. Ruch. ‘‘Arthroscopic
Resection of the Common Extensor Origin: Anatomic
Considerations.’’ Journal of Shoulder and Elbow
Surgery 12 (July-August 2003): 375–379.
Walther, M., S. Kirschner, A. Koenig, et al. ‘‘Biomechanical
Evaluation of Braces Used for the Treatment of
Epicondylitis.’’ Journal of Shoulder and Elbow Surgery
11 (May-June 2002): 265-270.
Wang, A. A., E. Whitaker, D. T. Hutchinson, and D. A.
Coleman. ‘‘Pain Levels After Injection of
Corticosteroid to Hand and Elbow.’’ American Journal
of Orthopedics 32 (August 2003): 383–385.
ORGANIZATIONS

motion should be avoided. Once pain decreases to the
point that return to activity can begin, the playing of
sports, such as tennis, for long periods should not
occur until excellent condition returns. Many times,
choosing a different size or type of tennis racquet may
help. Frequent rest periods are important despite what
the wrist and forearm activity may be. Compliance
with a stretching and strengthening program is very
important in helping prevent recurring symptoms and
exacerbation.

American College of Occupational and Environmental
Medicine (ACOEM). 1114 North Arlington Heights
Road, Arlington Heights, IL 60004. (847) 818-1800.
<www.acoem.org>.
American College of Sports Medicine. P.O. Box 1440,
Indianapolis, IN 46206-1440. (317) 637-9200. <http://
www.acsm.org>.

Jeffrey P. Larson, RPT
Rebecca J. Frey, PhD

TENS see Electrical nerve stimulation

Resources
PERIODICALS

Altay, T., I. Gunal, and H. Ozturk. ‘‘Local Injection
Treatment for Lateral Epicondylitis.’’ Clinical
Orthopedics 398 (May 2002): 127-130.
Das, D., and N. Maffulli. ‘‘Surgical Management of Tennis
Elbow.’’ Journal of Sports Medicine and Physical Fitness
42 (June 2002): 190-197.
de Seze, M. P., M. de Seze, P. Dehail, et al. ‘‘Botulinum
Toxin A and Musculoskeletal Pain.’’ [in French]
Annales de re´adaptation et de me´decine physique 46
(July 2003): 329–332.
Haake, M., I. R. Boddeker, T. Decker, et al. ‘‘Side-Effects of
Extracorporeal Shock Wave Therapy (ESWT) in the
Treatment of Tennis Elbow.’’ Archives of Orthopaedic
and Trauma Surgery 122 (May 2002): 222-228.
Mackay, D., A. Rangan, G. Hide, et al. ‘‘The Objective
Diagnosis of Early Tennis Elbow by Magnetic
3642

Tensilon test
Definition
Tensilon is the trade name for edrophonium
chloride. The Tensilon test is an injection of edrophonium chloride used to diagnosis myasthenia gravis
(MG).

Purpose
Tensilon blocks the action of an enzyme, acetylcholinesterase, an important part of the system regulating neuromuscular transmission. To stimulate a
muscle, a nerve cell (neuron) releases the chemical
acetylcholine. To prevent prolonged muscle response
GALE ENCYCLOPEDIA OF MEDICINE

In myasthenia gravis, there are too few receptors
for acetylcholine on the muscle. The acetylcholine is
broken down before it can fully stimulate this reduced
number of receptors, and, as a result, the muscle is
weak. By blocking the action of acetylcholinesterase,
Tensilon prolongs the muscle stimulation, and temporarily improves strength. Increased strength following an injection of Tensilon strongly suggests a
dignosis of MG. The Tensilon test is most effective
when easily observed weakness is present, and is less
useful for vague or fluctuating complaints.

Precautions
The Tensilon test may cause heart rhythm
abnormalities, especially in those patients with preexisting conditions.

Description
The Tensilon test involves the intravenous injection of a small amount of Tensilon. The needle is left in
place. If no adverse reaction is observed within 30
seconds, an additional volume is injected. Results are
apparent within one minute.

KEY TERMS
Acetylcholine—a molecule released by neurons at
the neuromuscular junction that causes muscle
contraction.

Abnormal results
An obvious increase in strength in weakened muscles strongly suggests the diagnosis of myasthenia
gravis. The effect comes on very rapidly, and fades
within minutes.
Resources
ORGANIZATIONS

Muscular Dystrophy Association. 3300 East Sunrise Drive,
Tucson, AZ 85718. (800) 572-1717. <http://
www.mdausa.org>.
Myasthenia Gravis Foundation of America. 222 S.
Riverside Plaza, Suite 1540, Chicago, IL 60606. (800)
541-5454. <http://www.med.unc.edu>.

Richard Robinson

Preparation
Before the test, the patient must stop taking all
drugs that can inhibit acetylcholinesterase. The referring physician can advise on specific drugs the patient
is taking.

Aftercare
The effects of Tensilon subside quickly, and are
completely gone after 30-60 minutes. No aftercare is
needed.

Risks
Atrial fibrillation and bradycardia are possible in
sensitive individuals. The administering physician
must have appropriate resuscitative equipment
available.

Tension headache
Definition
This most common type of headache is caused by
severe muscle contractions triggered by stress or exertion. The American Council for Headache Education
(ACHE) estimates that 95% of women and 90% of
men in the United States and Canada have had at least
one headache in the past twelve months. Tension
headaches are considered a type of primary headache,
which means that they are not caused by another
medical condition or disorder.
Other names for tension headaches include muscle
contraction headache, ordinary headache, psychomyogenic headache, and stress headache.

Description
Normal results
In a patient without MG, the Tensilon test will not
produce an obvious increase in a previously weak
muscle. Some subjective feelings of increased strength
are possible but not significant.
GALE ENCYCLOPEDIA OF MEDICINE

While most American adults get a tension headache from time to time, women and people with more
education are slightly more likely to suffer with them;
the female: male ratio is reported to be 1.4: 1. People
who are so anxious that they grind their teeth or hunch
3643

Tension headache

to a single nerve signal, acetylcholine is broken down
by acetylcholinesterase after the muscle is stimulated.

Tension headache

their shoulders may find that the physical strain in
their body can be experienced as pain and tension in
the muscles of the neck and scalp, producing almost
constant pain.
In terms of age groups, chronic tension headaches
have been reported in children younger than six years,
but most people report that their tension headaches
start in adolescence or the early twenties.

Causes and symptoms
Tension headaches are caused by tightening in the
muscles of the face, neck and scalp because of stress or
poor posture. They can last for days or weeks and can
cause pain of varying intensity. The tightening muscles
cause more expansion and constriction of blood vessels, which can make head pain worse. Eyestrain
caused by dealing with a large amount of paperwork
or reading can cause a tension headache as well.
Many people report tension headache pain as a
kind of steady ache (as opposed to a throb) that forms
a tight band around the forehead, affecting both sides
of the head. Tension headaches usually occur in the
front of the head, although they also may appear at the
top or the back of the skull.
Tension headaches often begin in late afternoon
and can last for several hours; they can occur every day
and last throughout most of the day, but most (82%)
go away within a few hours. A tension headache that
occurs on 15 or more days per month over a period of
six months or longer is called a chronic tension headache. Unlike migraines, tension headaches don’t cause
nausea and vomiting, sensitivity to light, or any kind of
aura before the headache begins.
It is possible for children as well as adults to have
more than one type of headache. It is not unusual for
patients with chronic tension headaches to suffer from
migraine headaches as well.

Diagnosis
Diagnosis of tension headaches is made from a
medical history, discussion of symptoms, and elimination of other types of headaches or underlying
disorders.
Very few headaches are the sign of a serious
underlying medical problem. However, sufferers
should call a physician at once if they:


have more than three headaches a week



take painkillers almost every day



need more than the recommended dose of painkiller

3644



have a stiff neck and/or fever in addition to headache



are dizzy, unsteady, or have slurred speech, weakness, or numbness



have confusion or drowsiness with the headache



have headaches that began with a head injury



have headaches triggered by bending, coughing or
exertion



have headaches that keep getting worse



have severe vomiting with the headache



have the first headache after age 50



awaken with headache that gets better as the day
goes on

Treatment
There are many different treatments for tension
headaches, which respond well to both medication and
massage. If these headaches become chronic, however,
they are best treated by identifying the source of tension and stress and reducing or eliminating it.
Medication
Tension headaches usually respond very well to
such over-the-counter analgesics as aspirin, ibuprofen,
or acetaminophen. However, some of these drugs
(especially those that contain caffeine) may trigger
rebound headaches if discontinued after they are
taken for more than a few days.
More severe tension headaches may require combination medications, including a mild sedative such
as butalbital; these should be used sparingly, though.
Chronic tension headaches may respond to low-dose
amitriptyline taken at night.
Massage
Massaging the tense muscle groups may help ease
pain. Instead of directly massaging the temple,
patients will get more relief from rubbing the neck
and shoulders, because tension headaches can arise
from tension in this area. In fact, relaxing the muscles
of the neck can cut the intensity and duration of tension headaches at least in half.
To relax these muscles, the neck should be rotated
from side to side as the shoulders shrug. Some people
find that imagining a sense of warmth or heaviness in
the neck muscles can help. Taking three very deep
breaths at the first hint of tension can help prevent a
headache.
GALE ENCYCLOPEDIA OF MEDICINE

Analgesic—A medication that relieves pain without causing loss of consciousness. Over-the-counter analgesics include aspirin and NSAIDs.
Primary headache—A headache that is not caused
by another disease or medical condition. Tension
headaches are a subtype of primary headache.
Rebound headache—A type of primary headache
caused by overuse of pain relievers. It is also known
as analgesic abuse headache.

Areas of pain

Prognosis
Cutting down on stress and relying less on caffeine-containing medications can reduce the number
of tension headaches for most people.

Tension Headache
Tension headache is the most common type of headache
caused by severe muscle contractions triggered by stress
or exertion. Tension headaches usually occur in the front of
the head, although they may also appear at the top or the back
of the skull, as shown in the illustration above. (Illustration by
Electronic Illustrators Group.)

Prevention
Tension headaches can often be prevented by
managing everyday stress and making some important
lifestyle changes. Those who are prone to tension
headaches should:


take frequent ‘‘stress breaks’’



get regular exercise—even a brisk 15-minute walk
can help prevent tension headaches



get enough sleep



release angry feelings

Other therapy
If tension headaches are a symptom of either
depression or anxiety, the underlying problem should
be treated with counseling, medication, or a combination of both.
Injections of botulinum toxin (Botox) have been
reported to relieve tension headaches in some patients,
but this treatment is still regarded as experimental as
of 2004.

Alternative treatment
Eliminating the source of the tension as much as
possible will help prevent tension headaches.
Acupuncture may be helpful in treating some chronic
tension headaches. Homeopathic remedies and botanical medicine can also help relieve tension headaches.
Valerian (Valeriana officinalis), skullcap (Scutellaria
lateriflora), and passionflower (Passiflora incarnata)
are three herbal remedies that may be helpful. A tension headache can also be relieved by soaking the feet
in hot water while an ice cold towel is wrapped around
the neck.
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Headache.’’ In The Merck Manual of Diagnosis and
Therapy. Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Headache.’’ New York: Simon & Schuster, 2002.
PERIODICALS

Argoff, C. E. ‘‘The Use of Botulinum Toxins for Chronic
Pain and Headaches.’’ Current Treatment Options in
Neurology 5 (November 2003): 483–492.
Balottin, U., F. Nicoli, G. Pitillo, et al. ‘‘Migraine and
Tension Headache in Children under 6 Years of Age.’’
European Journal of Pain 8 (August 2004): 307–314.
Headache Classification Subcommittee of the International
Headache Society. ‘‘The International Classification of
Headache Disorders,’’ 2nd ed. Cephalalgia 24,
Supplement 1 (2004): 1–150.
3645

Tension headache

KEY TERMS

Muscles

Testicular cancer

Padberg, M., S. F. de Bruijn, R. J. de Haan, and D. L. Tavy.
‘‘Treatment of Chronic Tension-Type Headache with
Botulinum Toxin: A Double-Blind, Placebo-Controlled
Clinical Trial.’’ Cephalalgia 24 (August 2004): 675–680.
Seshia, S. S. ‘‘Mixed Migraine and Tension-Type: A
Common Cause of Recurrent Headache in Children.’’
Canadian Journal of Neurological Sciences 31 (August
2004): 315–318.
Singh, Manish K., MD. ‘‘Muscle Contraction Tension
Headache.’’ eMedicine October 5, 2001. <http://
www.emedicine.com/neuro/topic231.htm>.
ORGANIZATIONS

American Headache Society (AHS). 19 Mantua Road, Mt.
Royal, NJ 08061. (856) 423-0043. Fax: (856) 4230082.<http://www.ahsnet.org>.
National Headache Foundation. 428 W. St. James Place,
Chicago, IL 60614. (800) 843-2256. <http://
www.headaches.org>.
National Institute of Neurological Disorders and Stroke
(NINDS). ‘‘Headache—Hope Through Research.’’
Bethesda, MD: NINDS, 2001. <http://www.ninds
.nih.gov/health_and_medical/pubs/headache_htr>.

Carol A. Turkington
Rebecca J. Frey, PhD

Terazosin see Alpha1-adrenergic blockers

Testicular cancer
Definition
Testicular cancer is a disease in which cancer cells
are discovered in one or both testicles. The testicles,
also known as testes or gonads, are located in a pouch
beneath the penis called the scrotum.

Description
The testicles make up one portion of the male
reproductive system. Normally, they are each somewhat smaller than a golf ball in size and are contained
within the scrotum. The testicles are a man’s primary
source of male hormones, particularly testosterone.
They also produce sperm.
There are several types of cells contained in the
testicles, and any of these may develop into one or
more types of cancer. Over 90% of all testicular cancers begin in cells called germ cells. There are two main
types of germ cell tumors in men: seminomas and
nonseminomas. Seminomas make up about 40% of
all testicular germ cell tumors. Nonseminomas make
3646

up a group of cancers, which include choriocarcinoma,
yolk sac tumors, embryonal carcinoma, and teratoma.
Although testicular cancer accounts for less then
2% of all cancers in men, it is the most commonly seen
cancer in young men aged 15 to 35. It is also one of the
most curable.
The American Cancer Society estimates that
approximately 8,980 new cases of testicular cancer
will be diagnosed in American men in 2004. In addition, about 360 men will die of the disease during that
year. Although the incidence of testicular cancer is
rising, having doubled since 1975, it is still rare.
Scandinavian countries have the highest rate in the
world. Germany and New Zealand also have high
rates. The lowest incidences of testicular cancer are
in Asia and Africa.

Causes and symptoms
The exact causes of testicular cancer are
unknown. However, there is research showing that
some men are more likely to acquire it than others.
The risk for testicular cancer is much higher for boys
born with one or both of their testicles located in the
lower abdomen rather than in the scrotum. This condition is called cryptorchidism or undescended testicles. The lifetime risk of getting testicular cancer is
four times higher for boys with cryptorchidism than
the risk in the general population. This risk factor
remains even if surgery is done to place the testicle
back into the scrotum.
Boys born with Down syndrome are also at higher
risk of developing testicular cancer, although the reasons for this increased risk are not yet fully understood
as of 2004.
There are other risk factors as well. Men who have
had abnormal development of their testicles are at
increased risk, as are men with Klinefelter’s syndrome
(a disorder of the sex chromosomes). A family history
of testicular cancer increases the possibility of getting
the disease. Men infected with the human immunodeficiency virus (HIV), especially those with AIDS, have
a higher incidence, as do infertile men. Certain testicular tumors appear more frequently among men who
work in certain occupations, like miners, oil workers,
and utility workers. There is no conclusive evidence
that injuries to the testicles or environmental exposure
to various chemicals cause the disease.
Testicular cancer usually shows no early symptoms. It is suspected when a mass or lump is felt in
the testes, although a testicular mass does not always
indicate cancer and is usually painless.
GALE ENCYCLOPEDIA OF MEDICINE



a lump in either testicle (usually pea-sized, but may
be as large as a marble or an egg)



any enlargement or significant shrinking of a
testicle



a sensation of heaviness in the scrotum



a dull ache in the groin or lower abdomen



any sudden collection of fluid in the scrotum



tenderness or enlargement of the breasts



pain or discomfort in a testicle or in the scrotum

Diagnosis
When a man exhibits symptoms that suggest
a possibility of testicular cancer, several diagnostic
steps will occur before a definitive diagnosis is made.

Surgery
If a suspicious growth is found, a surgeon will
need to remove the tumor and send it to the laboratory
for testing. A pathologist examines the testicular tissue
microscopically to determine whether cancer cells are
present. If cancer cells are found, the pathologist sends
back a report describing the type and extent of the
cancer. In almost all cases, the surgeon removes the
entire affected testicle through an incision in the groin,
though not through the scrotum. This procedure is
called radical inguinal orchiectomy.
Once testicular cancer is determined, further tests
are necessary to find out if the cancer has metastasized
(spread) to other parts of the body, and to ascertain
the stage or extent of the disease. This information
helps the doctor plan appropriate treatment. These
tests may include computed tomography (CT scan),
lymphangiography (x rays of the lymph system), bone
scans, and chest x rays.

History and physical
The physician takes a personal and family medical
history and a complete physical examination is performed. The doctor will examine the scrotum as well
as the abdomen and other areas to check for additional masses.
Imaging studies
If a mass is found, the physician will likely have an
ultrasound performed. Through the use of sound
waves, ultrasounds can help visualize internal organs
and may be useful in telling the difference between
fluid-filled cysts and solid masses. If the tumor is
solid, it is most likely cancerous.
Computed tomography as well as ultrasound may
be used to diagnose malignant germ cell tumors in
undescended testes.
Blood tests
Certain blood tests can be helpful in diagnosing
some testicular tumors. Tumor markers are substances
often found in higher-than-normal amounts in cancer
patients. Some testicular cancers secrete high levels of
certain proteins such as alpha-fetoprotein (AFP),
human chorionic gonadotropin (HCG), and enzymes
like lactate dehydrogenase (LDH). These markers
may help find a tumor that is too small to be felt
during a physical examination. In addition, these
tests are also helpful in determining how much cancer
is actually present, and in evaluating the response to
treatment to make sure the tumor has not returned.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Staging
One method the cancer treatment team uses to
describe the scope of a patient’s cancer is the use of a
staging system. Testicular cancer is classified using the
TNM system. However, in order to simplify and summarize this information, the TNM description can be
grouped according to stages.
Stages of testicular cancer:


Stage I. This stage refers to a cancer found only in the
testicle, with no spread to the lymph nodes or to
distant organs.



Stage II. This indicates that the cancer has spread to
the lymph nodes in the abdomen, but not to lymph
nodes in other parts of the body.



Stage III. In this stage, the cancer has spread beyond
the lymph nodes in the abdomen, and/or the cancer is
in parts of the body far away from the testicles, such
as the lungs or the liver.



Recurrent. Recurrent disease indicates that the cancer has come back after it has already been treated.
Testicular cancer can come back in the same testicle
(if it was not surgically removed) or in some other
body part.
Treatment

The treatment decisions for testicular cancer are
dependent on the stage and cell type of the disease, as
3647

Testicular cancer

Symptoms:

Testicular cancer

Penis

Site of
cancer

Testicle
Scrotum

A cancerous growth on the testicle. (Illustration by Argosy Inc.)

well as the patient’s age and overall health. The four
kinds of treatment most commonly used are surgery,
radiation therapy, chemotherapy, and bone marrow or
stem cell transplantation.
Surgery is normally the first line of treatment for
testicular cancer and involves the removal of the
affected testicle. This procedure is known as a radical
inguinal orchiectomy. Depending on the type and
stage of the cancer, some lymph nodes may also be
removed at the same time, or possibly in a second
operation. This procedure is called a retroperitoneal
lymph node dissection, and can be a major operation.
Some patients will experience temporary complications after surgery, including infections and bowel
obstruction. If both of the testicles are taken out, a
man will have no ability to produce sperm cells and
will become infertile (unable to father a child). Surgery
removing the lymph nodes may cause some damage to
nearby nerves, which may interfere with the ability to
ejaculate. Men undergoing surgery for testicular cancer may wish to discuss nerve-sparing surgery with
their doctor, as well as sperm banking.
Radiation therapy for testicular cancer is delivered from a machine and is known as external beam
3648

radiation. One potential problem with this type of
radiation is that it can also destroy nearby healthy
tissue as well as cancer cells. Other potential side
effects include nausea, diarrhea and fatigue. A special
device can be used to protect the unaffected testicle to
preserve fertility.
Chemotherapy refers to the use of drugs in treating cancer. Since the drugs enter the bloodstream and
circulate throughout the body, chemotherapy is considered a systemic treatment. The drugs primarily used
in the treatment of testicular cancer are cisplatin, vinblastine, bleomycin, cyclophosphamide, etoposide,
and ifosfamide. These drugs are given in various combinations, since the use of two or more drugs is considered more effective than using only one drug.
Since chemotherapy agents can affect normal as
well as cancerous cells, several side effects are possible.
These side effects include:


nausea and vomiting



changes in appetite



hair loss (temporary)



mouth sores
GALE ENCYCLOPEDIA OF MEDICINE

increased risk of infections



bleeding or bruising



fatigue



diarrhea or constipation

Several drugs are available to assist in treating
these side effects, most of which will disappear after
the treatment is completed. However, some of the
chemotherapy agents used during treatment of testicular cancer may cause long-term side effects. These
include hearing loss, nerve damage, and possible kidney or lung damage. Another potentially serious
long-term complication is an increased risk of leukemia. This is a rare side effect, however, as it occurs in
less than 1% of testicular cancer patients who receive
chemotherapy. Chemotherapy may also interfere
with sperm production. This may be permanent for
some, but many will regain their fertility within a
few years.
Studies are ongoing to determine whether high
doses of chemotherapy combined with stem-cell transplantation will prove effective in treating some
patients with advanced testicular cancer. In this treatment, blood-forming cells called stem cells are taken
from the patient (either from the bone marrow or
filtered out of the patient’s blood). These cells are
kept frozen while high-dose chemotherapy is administered. After receiving the chemotherapy, the patient is
given the stem cells through an infusion. This treatment enables the use of extra large doses of chemotherapy that might increase the cure rate for some
testicular cancers.
Preferred treatment plans by stage of disease
Stage I: Stage I seminomas are normally treated
with a radical inguinal orchiectomy followed by radiation treatment aimed at the lymph nodes. More than
95% of Stage I seminomas are cured through this
method. Another approach is to perform surgery
only. Patients are then followed closely for several
years with blood tests and imaging studies. If the cancer
spreads later on, radiation or chemotherapy can still be
used. Stage I non-seminomas are also highly curable
with surgery, followed by one of three options. These
options include the performance of a retroperitoneal
lymph node dissection, two cycles of chemotherapy, or
careful observation for several years.
Stage II: Stage II seminomas and non-seminomas are cured in 90% to 95% of the cases. For the
purposes of treatment, stage II testicular cancers are
classified as either bulky or nonbulky. Nonbulky
seminomas (no lymph nodes can be felt in the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cryptorchidism—Occurs when a boy is born with
one or both testicles in the lower abdomen rather
than the scrotum. Known also as undescended testicles, it is the primary risk factor for testicular
cancer.
Metastatic testicular cancer—Testicular cancer
that has spread to other parts of the body.
Radical inguinal orchiectomy—Surgical procedure performed to remove one or both testicles.
It is done via a groin incision.
Testicles—Also called testes or gonads, they are
part of the male reproductive system, and are
located beneath the penis in the scrotum.

abdomen) are treated with an orchiectomy followed
by radiation to the lymph nodes. Men with bulky
seminomas have surgery, which may be followed by
either radiation or a course of chemotherapy.
Nonbulky Stage II non-seminomas are treated with
surgery and lymph node removal, with possible chemotherapy. Men with bulky disease have surgery
followed by chemotherapy.
Stage III: Stage III seminomas and non-seminomas are treated with surgery followed by chemotherapy. This produces a cure in about 70% of the cases.
Those who are not cured may be eligible to participate
in clinical trials of other chemotherapy agents.
Recurrent: Treatment of recurrent testicular cancer is dependent upon the initial stage and the treatment given. This might include further surgery and
chemotherapy. Many men whose disease comes back
after chemotherapy are treated with high-dose chemotherapy followed by bone marrow or stem cell
transplantation.
As of 2004, there is growing evidence that men
treated with cisplatin for testicular cancer are at
increased risk of coronary artery disease ten years or
longer after treatment. In addition, men who have had
an orchiectomy followed by external beam radiation
therapy have a significantly increased risk of dying
from heart disease or a second cancer.

Alternative treatment
There are currently no scientifically proven alternative treatments known for testicular cancer.
Nothing has been shown to be as successful as
3649

Testicular cancer



Testicular self-examination

conventional treatment. However, some patients may
find certain alternative or complementary treatments
supportive while undergoing surgery, chemotherapy
or radiation. For example, meditation and relaxation
exercises may prove effective in reducing nausea and
vomiting. Some dietary modifications and nutritional
supplements may be helpful in assisting with recovery
after surgery. The testicular cancer patient considering
alternative treatments should talk it over with members of the cancer care team. They may be able to offer
additional information.

OTHER

American Cancer Society (ACS). Cancer Facts & Figures
2004. <http://www.cancer.org/downloads/STT/
CAFF_finalPWSecured.pdf>.
Beeson, Dr. Debra. ‘‘Commentary: Testicular Cancer
Commonly Seen in Younger Men.’’ Cancer News. April
12, 2000. [cited June 19, 2001]. <http://www.ontumor
.com/cancernews_sm/testicular041200.htm>.
National Cancer Institute CancerNet. June 19, 2001.
<http://www.Cancernet.nci.nih.gov>.
The Testicular Cancer Resource Center. June 19, 2001.
<http://www.acor.org/TCRC>.

Deanna M. Swartout-Corbeil, R.N.
Rebecca J. Frey, PhD

Prevention
The main risk factors associated with testicular
cancer—cryptorchidism, family history of the disease,
and being Caucasian—are unavoidable since they are
present at birth. In addition, many men diagnosed
with the disease have no known risk factors. Because
of these reasons, it is not possible to prevent most
incidences of testicular cancer.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Testicular Cancer.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ: Merck
Research Laboratories, 2004.
Nichols, Craig R., et al. ‘‘Neoplasms of the Testis.’’ In
Cancer Medicine. 5th ed. Hamilton, Ontario: American
Cancer Society, 2000.
PERIODICALS

Mercer, E. S., B. Broecker, E. A. Smith, et al. ‘‘Urological
Manifestations of Down Syndrome.’’ Journal of
Urology 171 (March 2004): 1250–1253.
Muttarak, M., W. C. Peh, and B. Chaiwun. ‘‘Malignant
Germ Cell Tumours of Undescended Testes: Imaging
Features with Pathological Correlation.’’ Clinical
Radiology 59 (February 2004): 198–2004.
Nuver, J., A. J. Smit, D. T. Sleijfer, et al.
‘‘Microalbuminuria, Decreased Fibrinolysis, and
Inflammation as Early Signs of Atherosclerosis in
Long-Term Survivors of Disseminated Testicular
Cancer.’’ European Journal of Cancer 40 (March 2004):
701–706.
Zagars, G. K., M. T. Ballo, A. K. Lee, and S. S. Strom.
‘‘Mortality after Cure of Testicular Seminoma.’’
Journal of Clinical Oncology 22 (February 18, 2004):
640–647.

Testicular scan see Scrotal nuclear medicine
scan

Testicular self-examination
Definition
A testicular self-examination (TSE) is the procedure by which a man checks the appearance and consistency of his testes.

Purpose
Most testicular cancers are first noticed by the
man himself. Men should do a TSE every month to
find out if the testes contain any suspicious lumps or
other irregularities, which could be signs of cancer or
infection.

Precautions
None.

Description

ORGANIZATIONS

A TSE should take place during a warm shower or
bath, when the skin is warm, wet, and soapy. The man
needs to step out of the tub so that he is in front of a
mirror. The heat from the tub or shower will relax the
scrotum (sac containing the testes) and the skin will be
softer and thinner, making it easier to feel a lump. It is
important that the exam be done very gently.

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800) ACS-2345. <http://www.cancer.org>.
National Cancer Institute. Cancer Information Service.
(800) 4-CANCER.

The man should stand facing his mirror and look
for swelling on the scrotum. Using both hands, the
scrotum should be gently lifted so that the area underneath can be checked.

3650

GALE ENCYCLOPEDIA OF MEDICINE

Seidel, Henry M., et al. Mosby’s Guide to Physical
Examination. 4th ed. St. Louis: Mosby, Inc., 1999.
OTHER

Epididymis—A tube in the back of the testes that
transports sperm.
Scrotum—The pouch containing the testes.
Testes—Egg-shaped male gonads located in the
scrotum. Testes is the plural form of testis, which
is a testicle.
Vas deferens—A tube that is a continuation of the
epididymis. This tube transports sperm from the
testis to the prostatic urethra.

The next step is examination by hand. The index
and middle fingers should be placed under each testicle, with the thumbs on top. The testes should be
examined one at a time. The man should roll each
testicle between his fingers and thumbs. He should
feel for lumps of any size (even as small as a pea)
particularly on the front or side of each testicle. He
should also look for soreness or irregularities. Next,
the epididymis and vas deferens, located on the top
and back of the testes, should be felt. This area feels
like a cord, and should not be tender.

‘‘Questions and Answers About Testicular Cancer.’’
National Cancer Institute. February 2000. <http://
cis.nci.nih.gov/fact/6_34.htm>.

Rhonda Cloos, R.N.

Testicular sonsgram see Scrotal ultrasound

Testicular surgery
Definition
Testicular surgery is any surgical operation on the
testicles.

Purpose
Testicular surgery is used primarily to correct
developmental defects, treat infection or trauma, and
treat cancer of the testes.

Precautions
Normal results
It is normal for one testicle to be larger than the
other is, and for them to hang at different levels; but
the size should stay the same from one month to the
next. The testes should be free from lumps, pain, irregularities and swelling.

Abnormal results
A TSE is considered abnormal if any swelling,
tenderness, lumps, or irregularities are found. Hard,
unmoving lumps are abnormal, even if they are painless. A lump could be a sign of an infection or a
cancerous tumor. A change in testicle size from one
month to the next is also abnormal. A feeling of heaviness in the scrotum is another abnormal sign. If any
abnormality is found, a man is encouraged to check
with his doctor as soon as possible because testicular
cancer is highly curable if found early.
Resources
BOOKS

Hainsworth, John D., and F. Anthony Greco. ‘‘Testis.’’ In
Cancer Treatment, edited by Charles M. Haskell, 5th
ed. Philadelphia: W.B. Saunders, 2001.
GALE ENCYCLOPEDIA OF MEDICINE

Testicular surgery, a group of surgical operations
performed on the testicles, is considered major surgery. In all cases, except when the testes are being
removed, care must be taken not to damage any of
the nerves and blood vessels supplying the testes and
associated organs.

Description
Testicular surgery is commonly performed for the
following reasons: to reposition undescended testes
(orchiopexy); to correct testicular torsion; to treat testicular cancer, which may involve removal of the testicles (castration) or the testes (orchiectomy); to treat
traumatic injuries of the testicles; and to correct intersex states.
Undescended testes
Undescended testes are testes that have not
dropped into the scrotum. During the fetal stage of
development, the testes are not in the scrotum, but in
the body. As male children age, the testes descend
from the body to the scrotum for proper maturation
and function. Undescended testes must be treated with
surgery. There are two types of undescended testes,
3651

Testicular surgery

KEY TERMS

Testicular surgery

ectopic and cryptorchid. Ectopic testes are outside the
normal route of descent. Cryptorchid testes are in the
proper route of descent, but descent has been stopped
before the testes reached the scrotum. The treatment
for undescended testes is a surgical operation called
orchiopexy, in which an incision allows the surgeon to
reach the testes and pull them down into the scrotum.
This operation is best done between the ages of one
and two; otherwise, the testes are unlikely to mature
normally. If the patient has one normal testis and one
poorly developed testis, the undeveloped testis is
usually removed.
Testicular torsion
Testicular torsion is a developmental defect in the
tissues of the scrotum that allows the testes to rotate
within the scrotum. This results in the blood vessels
around other tubes in the scrotum to become wrapped
around each other, resulting in blood supply to the
testes bring cut off. Torsion disease is seen in young
boys. Pain, nausea, and scrotal swelling are the main
symptoms. When torsion is suspected, immediate surgery is recommended. An incision is made in the scrotum, and the blood vessels and other tissues are
untangled. During surgery, the testes are examined
to determine their condition. If they have received
enough blood to remain viable, the testes are surgically
attached to scrotal tissue to prevent twisting from
recurring. If the testes do not regain a healthy pink
color after the blood vessels have been untangled, then
it is best to remove the testes. The lack of a pink color
indicates that the testes have been without blood for
too long a time period, and are dead tissue. Unless
removed, they will turn necrotic and cause further
harm to the body. Usually, testicular torsion occurs
in only one testis. However, because the other testicle
has similar anatomy, it too is subject to torsion.
During surgery, the other testicle is attached to scrotal
tissue to prevent torsion from occurring.
Cancer
Carcinoma of the testes is the medical term for
cancer of the testicles. For males between ages 20–35,
carcinoma of the testes is the second most common
cancer. It accounts for 1–2% of all cancers in all males.
There are many kinds of cancer that can affect the
testes. A mass of tissue that is suspected to be cancer
should be removed surgically. It is recommended that
a biopsy not be performed, but that the physician
proceed directly to surgery. Biopsies have not proven
to be better at diagnosing cancer of the testicles than
exploratory surgery. If the presence of cancer is
3652

confirmed during exploratory surgery, surgical excision of the cancer can be performed immediately.
The approach to the cancer during the operation
depends on the location of the tissue mass. The two main
approaches are through the scrotum and through the
groin (inguinal region). The amount of tissue removed is
variable and depends on the amount of cancerous tissue
and the location. However, if a solid lesion is confirmed
within a testis, a radical orchiectomy should be performed. A radical orchiectomy is a complete removal
of one or both testes and associated lymphatic tissue.
Other tumors allow partial removal of a testis. After
surgery, the tumor is examined to determine the type
of tumor for use as a guide in followup therapy.
Castration is the surgical removal of the testicles.
Castration is performed as a cancer therapy, to reduce
the amount of testosterone being produced, and as
part of treatment for prostate cancer. In castration,
an incision is made through one or both sides of the
scrotum, depending on whether one or both testicles
are being removed.
Trauma
Traumatic injuries to the testes may involve penetrating gunshot or knife wounds; explosions and other
industrial accidents; and athletic injuries. Dislocation
of the testes is a potential complication of blunt
trauma to the abdomen, which commonly occurs in
automobile or motorcycle accidents. A dislocated testis can usually be identified by either ultrasound or CT
scans of the patient’s pelvis.
Intersex states
Intersex states are a group of developmental diseases in which the patient has parts of both male and
female genitalia. In testicular feminization syndrome,
the patient appears to be a female and will have female
genitalia but has internal testes. The internal testes are
undescended. Genetic studies show that the person was
to be a male. This form of intersex is also called male
pseudohermaphroditism. There are a number of different causes of this condition. These patients produce the
male hormone testosterone. Treatment consists of surgical removal of the internal testes, and the administration of the hormone estrogen, which produces female
characteristics. Failure to remove the testes is associated with a higher rate of cancer in these patients.

Preparation
About one hour before receiving general anesthesia, the patient will get a shot that dries up internal
GALE ENCYCLOPEDIA OF MEDICINE

Biopsy—Removing tissue to test it for disease.
Lesion—An injury in the body tissue, such as a
wound, sore, rash, or boil.
Orchiectomy—Surgical removal of one or both
testes.
Orchiopexy—Surgical fixation of one or both
testes.
Testes—The pair of male reproductive glands
enclosed in the scrotum that produce the male sex
hormone testosterone and the spermatozoa. The
singular form is testis.
Testicles—The testes along with their enclosing
structures.

PERIODICALS

Fossa, S. D. ‘‘Long-Term Sequelae after Cancer Therapy—
Survivorship after Treatment for Testicular Cancer.’’
Acta Oncologica 43 (February 2004): 134–141.
Ko, S. F., S. H. Ng, Y. L. Wan, et al. ‘‘Testicular
Dislocation: An Uncommon and Easily Overlooked
Complication of Blunt Abdominal Trauma.’’ Annals of
Emergency Medicine 43 (March 2004): 371–375.
Shukla, A. R., C. Woodard, M. C. Carr, et al. ‘‘Experience
with Testis Sparing Surgery for Testicular Teratoma.’’
Journal of Urology 171 (January 2004): 161–163.
Zagars, G. K., M. T. Ballo, A. K. Lee, and S. S. Strom.
‘‘Mortality after Cure of Testicular Seminoma.’’
Journal of Clinical Oncology 22 (February 18, 2004):
640–647.
ORGANIZATIONS

American Urological Association (AUA). 1000 Corporate
Boulevard, Linthicum, MD 21090. (866) 746-4282 or
(410) 689-3700. <http://www.auanet.org>.

fluids and makes him sleepy. Presurgical counseling is
often recommended for patients whose reproductive
abilities will be compromised by their surgeries.

Rebecca J. Frey, PhD

Aftercare
A patient who has had a testicle removed should
visit his physician once a month for the first year and
every other month for the second year, with periodic
followups thereafter.

Testicular torsion
Definition

Risks
Testicular surgery, like any major surgery, can
have postoperative complications. These complications include internal bleeding and wound infection,
as well as adverse reactions to anesthesia. About 10–
15% of patients develop fertility problems.
As of 2004, there is growing evidence that men
who have had an orchiectomy followed by external
beam radiation therapy have a significantly increased
risk of dying from heart disease or a second cancer.

Normal results
Undescended testes are pulled down into their
correct position and mature normally. In testicular
torsion, the affected testis either regains its healthy
pink color and is attached to the surrounding tissue
with sutures, or it is removed along with any dead
tissue surrounding it. (So long as only one testis is
removed, sexual function and fertility will not be
affected.) Successful surgery for cancer results in the
removal of malignant tissue.
GALE ENCYCLOPEDIA OF MEDICINE

Testicular torsion is the twisting of a testis (testicle) on its connection.

Description
The testes are suspended in the scrotum by a single
bundle of tissues that also carries the blood supply to
and from the testes. If the testicle rotates, the bundle
kinks, and the blood supply is shut off. The resulting
situation is an emergency because the testis will die
within hours if the blood supply is not restored.

Causes and symptoms
Some testes hang in such a way that they twist
more easily than others. Nearly all torsions happen to
adolescent males–between the ages of 12 and 18–
because their testes enlarge by a factor of five to six
during puberty. A larger testis is more likely to twist.
Torsion can also occur in a newborn.
Symptoms of testicular torsion are sudden severe
pain in the scrotum, swelling, nausea and vomiting.
3653

Testicular torsion

Resources

KEY TERMS

Tetanus

KEY TERMS
Twisted
spermatic cord

Orchiopexy—The surgical securing of the testis to
prevent torsion.
Scrotum—The bag of skin below the penis that
contains the testes.

Testicle

Resources
BOOKS
Scrotum

Walsh, Patrick C., et al., editors. Campbell’s Urology.
Philadelphia: W. B. Saunders Co., 1998.

J. Ricker Polsdorfer, MD

Testicular ultrasound see Scrotal ultrasound
A rare condition, testicular torsion occurs when the spermatic cord is twisted and cuts off the blood supply to the
testicle. (Illustration by Argosy Inc.)

Testicular x ray see Scrotal nuclear medicine
scan
Testosterone test see Sex hormones tests

Diagnosis
A nuclear scan of the scrotum may be performed.
In this procedure, a tiny amount of radioactive fluid is
injected into the blood and detected as it flows through
the scrotum and testicles. Torsion is indicated if the
radioactive fluid does not flow through the sore testis.
Ultrasound scan accompanied by a contrast agent can
also be used to diagnose testicular torsion.

Treatment
Surgery must be performed within 24 hours to
ensure the health of the affected testis. During the
procedure, the surgeon untwists the cord and secures
the testis in place so that it cannot rotate again.
The other testicle should also be secured to deter
future testicular torsion. This procedure is called
orchiopexy.

Prognosis
If the torsion is relieved within 24 hours, the testis
will recover normal blood flow and function.

Prevention
Torsion of the unaffected testis is prevented by
securing it during the surgery to correct the twisted
testis.
3654

Tetanus
Definition
Tetanus is a rare but often fatal disease that affects
the central nervous system by causing painful muscular contractions. It begins when tetanus bacteria enter
the body, usually through a wound or cut exposed to
contaminated soil. Tetanus is easily preventable
through vaccination.

Description
Tetanus is rare in the United States, with nearly
all cases occurring in adults who were not vaccinated
as children. About 100 cases are reported each year;
63% of these occur in people over the age of 50. The
number of tetanus cases in the United States has
steadily decreased since the 1940s (500 to 600 cases
per year); the number of reported cases has remained
at approximately 50 to 100 cases per year since the
mid-1970s. In 1999, however, the lowest number of
annual cases to date was reported (33, or 0.02 per
100,000).
Tetanus causes convulsive muscle spasms and
rigidity that can lead to respiratory paralysis and
death. It is sometimes called ‘‘lockjaw’’ because one
of the most common symptoms is a stiff jaw, unable to
GALE ENCYCLOPEDIA OF MEDICINE

Tetanus

be opened. Sometimes, tetanus affects only the part of
the body where the infection began, but in almost all of
reported cases, it spreads to the entire body. The incubation period from the time of the injury until the first
symptoms appear ranges from two to 50 days.
Symptoms usually occur within five to 10 days.
When symptoms occur early, the chance of death is
increased. Tetanus is not contagious.

Causes and symptoms
Tetanus is caused by a bacteria called Clostridium
tetani, whose spores (the dormant form) are found in
soil, street dust, and animal (or even human) feces.
Tetanus spores germinate in the body, producing a
highly poisonous neurotoxin in the blood, spreading
to the nervous system. The infection is usually transmitted through deep puncture wounds or cuts or
scratches that are not cleaned well. Between 1997
and 1999, approximately 64% of tetanus cases in the
United States were associated with such wounds as
punctures, lacerations, or abrasions. Many people
associate tetanus with rusty nails and other dirty
objects, but any wound can be a source. Less common
ways of getting tetanus are animal scratches and bites,
surgical wounds, dental work, and therapeutic abortion. About 18% of cases reported between 1997 and
1999 were a result of intravenous drug use. Cases have
also been reported in people with no known wound or
medical condition.
The first symptom of tetanus is often a stiff or
‘‘locked’’ jaw that prevents the patient from opening
his/her mouth or swallowing. This is also called trismus and results in a facial expression called a sardonic
smile (or risus sardonicus). Stiffness of the neck and
other muscles throughout the body and uncontrollable spasms often follow. Sometimes these convulsions
are severe enough to cause broken bones. The bacterial toxin (tetanospasmin) affects the nerve endings,
causing a continuous stimulation of muscles. Other
symptoms include irritability, restlessness, loss of
appetite, and drooling. People with tetanus that is
localized experience pain and tingling only at the
wound site and spasms in nearby muscles.
In the underdeveloped world, neonatal tetanus
accounts for about one-half of tetanus deaths and is
related to infection of the umbilical stump in a baby
born of an unimmunized mother. The Centers for
Disease Control and Prevention (CDC) estimate that
over 270,000 deaths occur annually worldwide as a
result of neonatal tetanus. In contrast, only two cases
of neonatal tetanus in the United States were reported
to the CDC between 1989 and 1999. Mothers who
GALE ENCYCLOPEDIA OF MEDICINE

One characteristic of tetanus bacillus is the recurrent contracture of a muscle. Here, the patient’s left hand is affected.
(Custom Medical Stock Photo. Reproduced by permission.)

have been adequately immunized against tetanus protect their newborns by passing the antibody through
the placenta.

Diagnosis
Tetanus is diagnosed by the clinical symptoms
and a medical history that shows no tetanus immunization. Early diagnosis and treatment is crucial to
recovery from tetanus.

Treatment
Tetanus is a life-threatening disease that requires
immediate hospitalization, usually in an intensive care
unit (ICU). Treatment can take several weeks and
includes antibiotics to kill the bacteria and shots of
antitoxin to neutralize the toxin. It also includes muscle-relaxing drugs to control muscle spasms or barbiturates for sedation. In severe cases, patients are placed
on an artificial respirator. Recovery can take six weeks
or more. After recovery, since the levels of circulating
toxin are too low to stimulate natural antibody production, the patient must still be immunized against
this disease to prevent reinfection.

Prognosis
Up to 30% of tetanus victims in the United States
die. Early diagnosis and treatment improves the prognosis. Neonatal tetanus has a mortality rate of more
than 90%.
3655

Tetanus

Prevention

KEY TERMS

Pre-exposure vaccination
Tetanus is easily preventable through vaccination.
All children should have a series of five doses of DTaP,
a combined vaccine that offers protection against
diphtheria, tetanus, and pertussis, before the age of
seven, according to the Centers for Disease Control
and Prevention’s national immunization guidelines,
the Advisory Committee on Immunization Practices,
the Committee on Infectious Diseases of the American
Academy of Pediatrics, and the American Academy of
Family Physicians. Children will not be admitted to
school without proof of this and other immunizations.
The DTaP (diptheria, tetanus, accellular pertussis)
vaccine should be given at ages two months, four months,
six months, 15 to 18 months, and four to six years. DTaP
is the preferred vaccine for children up to the age of seven
in the United States; it has fewer side effects than DTP
and can be used to complete a vaccination schedule begun
with DTP. DTaP was first approved by the Food and
Drug Administration (FDA) in September 1996. In
December 1996, it was approved for use in infants.
Between the ages of 11 and 13, children should have a
booster for diphtheria and tetanus, called Td.
Adults should have a Td booster every 10 years.
Statistics from the Centers for Disease Control and
Prevention (CDC) show that fewer than half of
Americans 60 years of age and older have antibodies
against tetanus. The CDC suggests adults may be
revaccinated at mid-decade birthdays (for example,
45, 55). Adults who have never been vaccinated
against tetanus should get a series of three injections
of Td over six to 12 months and then follow the
10-year booster shot schedule.
Side effects of the tetanus vaccine are minor: soreness, redness, or swelling at the site of the injection that
appear anytime from a few hours to two days after the
vaccination and go away in a day or two. Rare but
serious side effects that require immediate treatment
by a doctor are serious allergic reactions or deep, aching
pain and muscle wasting in the upper arms. These
symptoms could start from two days to four weeks
after the shot and could continue for months.
In early 2001, a shortage of the tetanus vaccine
became evident after the pharmaceutical company
Wyeth-Ayerst Laboratories decided to stop production of the tetanus vaccine, leaving Aventis-Pasteur as
the sole manufacturer of the vaccine. As a result,
hospitals were provided with only a minimal amount
of the drug on a weekly basis—enough to vaccinate
patients with potentially infected wounds and other
3656

Clostridium—A genus of deadly bacteria that are
responsible for tetanus and other serious diseases,
including botulism and gangrene from war
wounds. Clostridia thrives without oxygen.
DTaP—Diphtheria and tetanus toxoids and accellular pertussis combination vaccine.
DTP— Diphtheria, tetanus, and whole-cell pertussis vaccine.
Td—Tetanus and diphtheria vaccine.
Toxin—A poisonous substance that flows through
the body.
Wound—Any injury that breaks the skin, including
cuts, scratches, and puncture wounds.

priority cases. Despite stepped-up production efforts
on the part of the manufacturer, however, a spokesperson
for Aventis-Pasteur predicted that the shortage would last
until the end of 2001, as the vaccine takes 11 months to
produce.
Post-exposure care
Keeping wounds and scratches clean is important
in preventing infection. Since this organism grows
only in the absence of oxygen, wounds must be adequately cleaned of dead tissue and foreign substances.
Run cool water over the wound and wash it with a
mild soap. Dry it with a clean cloth or sterile gauze. To
help prevent infection, apply an antibiotic cream or
ointment and cover the wound with a bandage. The
longer a wound takes to heal, the greater the chance of
infection. If the wound doesn’t heal, or, it is red, warm,
drains, or swells, consult a doctor.
Following a wound, to produce rapid levels of
circulating antibody, a doctor may administer a specific antitoxin (human tetanus immune globulin, TIG)
if the individual does not have an adequate history of
immunization. The antitoxin is given at the same sitting as a dose of vaccine but at separate sites. Some
individuals will report a history of significant allergy
to ‘‘tetanus shots.’’ In most cases, this occurred in the
remote past and was probably due to the previous use
of antitoxin derived from horse serum.
Resources
PERIODICALS

Landers, Susan J. ‘‘Tetanus vaccine shortage leads to
rationing.’’ American Medical News. March 19, 2001.
GALE ENCYCLOPEDIA OF MEDICINE

OTHER

‘‘Tetanus.’’ Centers for Disease Control and Prevention.
<http://www.cdc.gov/nip/publications/pink/
tetanus.pdf>.

Lori De Milto

infection for which it is being taken. The physician
who prescribed the drug or the pharmacist who filled
the prescription know the correct dosage.
To make sure the infection clears up completely,
patients are told to take the medicine for as long as it
has been prescribed. They should not stop taking the
drug just because symptoms begin to improve.
Tetracyclines work best when they are at constant
levels in the blood. To help keep levels constant, the
doses are spaced evenly through the day and night. No
doses should be missed.

Tetracyclines
Definition
Tetracyclines are medicines that kill certain infection-causing microorganisms.

Purpose
Tetracyclines are called ‘‘broad-spectrum’’ antibiotics, because they can be used to treat a wide variety
of infections. Physicians may prescribe these drugs to
treat eye infections, pneumonia, gonorrhea, Rocky
Mountain spotted fever, urinary tract infections, certain bacteria that could be used in biological weapons,
and other infections caused by bacteria. The medicine
is also used to treat acne. The tetracyclines will not
work for colds, flu, and other infections caused by
viruses. Tetracyclines are generally a low-cost alternative among antibiotics.
Interestingly, a form of tetracycline has recently
been used in prevention of cancer recurrence.
Chemically modified tetracyclines such as COL-3 are
derived from antibiotic tetracyclines, but because of
their modifications, don’t act as antibiotics. Instead,
they inhibit certain enzymes and processes that normally encourage cancer growth. By making cancer
cells less aggressive, these drugs may show potential
for long-term management of some cancers.

Description
Tetracyclines are available only with a physician’s
prescription. They are sold in capsule, tablet, liquid,
and injectable forms. Some commonly used medicines
in this group are tetracycline (Achromycin V,
Sumycin) and doxycycline (Doryx, Vibramycin).

Recommended dosage
The recommended dosage depends on the type of
tetracycline, its strength, and the type and severity of
GALE ENCYCLOPEDIA OF MEDICINE

This medicine works best when taken on an empty
stomach, with a full glass of water. The water will help
prevent irritation of the stomach and esophagus (the
tube-like structure that runs from the throat to the
stomach). If the medicine still causes stomach upset,
it may be necessary to take it with food. However,
tetracyclines should never be taken with milk or milk
products, as these may prevent the medicine from
working properly. Milk or dairy products should be
avoided within one to two hours of taking tetracyclines (except doxycycline and minocycline).

Precautions
Taking outdated tetracyclines can cause serious
side effects. The medicine should not be taken if:


its color, appearance, or taste have changed



it has been stored in a warm or damp area



the expiration date on its label has passed. Any such
medicine should be flushed down the toilet; if there is
any question about whether the medicine is still
good, the patient should check with a physician or
pharmacist

Antacids, calcium supplements, such as the salicylates Magan or Trilisate, magnesium-containing laxatives, or sodium bicarbonate (baking soda) should
not be taken within one to two hours of taking
tetracyclines.
Medicines that contain iron (including multivitamin and mineral supplements) should not be taken
within 2-3 hours of taking tetracyclines.
Some people feel dizzy when taking these drugs.
The medicine also may cause blurred vision. Because
of these possible effects, anyone who takes these drugs
should not drive, use machines or do anything else that
might be dangerous until they have found out how the
drugs affect them.
Birth control pills may not work properly while
tetracyclines are being taken. To prevent pregnancy,
3657

Tetracyclines

<http://www.ama-assn.org/sci-pubs/amnews/pick_01/
hlsb0319.htm>.

Tetracyclines

alternative methods of birth control should be used
while taking tetracyclines.

KEY TERMS

This medicine may increase sensitivity to sunlight.
Even brief exposure to sun can cause a severe sunburn
or rash. While being treated with this medicine, direct
sunlight should be avoided, especially between 10 A.M.
and 3 P.M. A hat and tightly woven clothing that covers
the arms and legs; a sunscreen with a skin protection
factor (SPF) of at least 15; protecting the lips with a
sun block lipstick; and avoiding use of tanning beds,
tanning booths, or sunlamps are advised when on
tetracyclines. The sensitivity to sunlight and sunlamps
may continue for two weeks to several months after
stopping the medicine.
Tetracyclines may permanently discolor the teeth
of people who took the medicine in childhood. The
drugs may also slow down the growth of children’s
bones. Tetracyclines are generally not given to infants
or children under 8 years of age unless directed by the
child’s physician. The medical community continues
to express concern about resistance to tetracyclines
and other antibiotics. As patients continue to use,
and often overuse, these medications, eventually,
strains of bacteria develop resistance to the medicines.
The use of tetracycline is much broader than it was 20
or 30 years ago and physicians will prescribe the medicine only when appropriate.
Special conditions
People with certain medical conditions or who are
taking certain other medicines may have problems if
they take tetracyclines. Before a patient takes these
drugs, the physician should be advised of any of
these conditions:
ALLERGIES. Anyone who has had unusual reactions to tetracyclines in the past should let his or her
physician know before taking the drugs again. The
physician also should be told about any allergies to
foods, dyes, preservatives, or other substances.
PREGNANCY. Pregnant women should not take
tetracyclines during the last half of pregnancy. These
drugs can prevent the baby’s bones and teeth from
developing properly and can cause the baby’s adult
teeth to be permanently discolored. The medicine also
can cause liver problems in pregnant women.
BREASTFEEDING. Women who are breastfeeding

should not take tetracyclines. The drugs pass into
breast milk and can affect the nursing baby’s teeth
and bones. They may also make the baby more sensitive to sunlight and may increase risk of fungal
infections.
3658

Gonorrhea—A sexually transmitted disease (STD)
that causes infection in the genital organs and may
cause disease in other parts of the body.
Microorganism—An organism that is too small to
be seen with the naked eye.
Rocky Mountain spotted fever—An infectious disease that is caused by a microorganism and spread
by ticks. High fever, muscle pain, and spots on the
skin are among the symptoms.
Salicylates—A group of drugs that includes aspirin
and related compounds. Salicylates are used to
relieve pain, reduce inflammation, and lower fever.

OTHER MEDICAL CONDITIONS. Before using tetracyclines, people with any of these medical problems
should make sure their physicians are aware of their
conditions:


diabetes



liver disease



kidney disease

USE OF CERTAIN MEDICINES. Taking tetracyclines
with certain other drugs may affect the way the drugs
work or may increase the chance of side effects.

Side effects
The most common side effects are stomach
cramps or a burning sensation in the stomach, mild
diarrhea, nausea, or vomiting. These problems usually
go away as the body adjusts to the drug and do not
require medical treatment. Less common side effects,
such as sore mouth or tongue and itching of the rectal
or genital areas also may occur and do not need medical attention unless they do not go away or they are
bothersome.
Other rare side effects may occur. Anyone who
has unusual symptoms during or after treatment with
tetracyclines should get in touch with his or her
physician.

Interactions
Tetracyclines may interact with other medicines.
When this happens, the effects of one or both of the
drugs may change or the risk of side effects may be
greater. Anyone who takes tetracyclines should let
a physician know all other medicines he or she is
GALE ENCYCLOPEDIA OF MEDICINE



antacids



calcium supplements



medicines that contain iron (including multivitamin
and mineral supplements)



laxatives that contain magnesium



cholesterol-lowering drugs such as cholestyramine
(Questran) and colestipol (Colestid)



salicylates such as Magan and Trilisate



penicillins



birth control pills

Tetralogy of Fallot

taking. Among the drugs that may interact with tetracyclines are:

Displaced aorta

Narrowed
pulmonary valve

Hole in
ventricular septum

Resources
PERIODICALS

‘‘Modified Tetracycline May Help Prevent Cancer
Recurrence.’’ Cancer Weekly December 10, 2002: 2.
Roberts, Marilyn C.‘‘Tetracycline Therapy: Update.’’
Clinical Infectious Diseases February 15, 2003: 462–466.

Nancy Ross-Flanigan
Teresa G. Odle

Tetralogy of Fallot
Definition
Tetralogy of Fallot is a common syndrome of
congenital heart defects.

Description
The heart is two pumps in one. The ventricle on
the left side pumps blood full of oxygen through the
body; the ventricle on the right side pumps the same
blood through the pulmonary artery to the lungs to
take up oxygen. The left ventricle operates at pressures
about four times as high as the right ventricle. Blood
is supposed to flow through one side, then the other.
Tetralogy of Fallot is a condition that is characterized by several congenital heart defects occurring
at once. They include:


ventricular septal defect (Abnormal passageway
between the right and left ventricles)



displaced aorta



narrowed pulmonary valve



thickened right ventricle wall

GALE ENCYCLOPEDIA OF MEDICINE

Thickened wall
of right ventricle

Tetralogy of Fallot is a common syndrome of congenital heart
defects. This condition, present in utero, is caused by the
narrowing of the pulmonary artery and a hole between the
ventricles. When the baby is born and begins to breathe on its
own, the baby turns cyanotic, or blue, due to the deoxygenated blood that bypasses the lungs because the narrowed
pathway and the hole between the ventricles has remained
open. (Illustration by Electronic Illustrators Group.)

Each defect acts in combination with the others to
create a malfunction of the heart. The problem starts
very early in the uterus with a narrowed pulmonary
valve and a hole between the ventricles. This is not
particularly a problem for a fetus because hardly any
blood flows through the lungs until birth. It is only
after birth that the defects pose a problem. The blood
that is supposed to start flowing through the lungs
cannot easily get there because of the narrowed
valve; however, the hole between the ventricles
remains open. Because of the opening between ventricles, much of the blood that comes back to the heart
needing oxygen is sent out without being properly
oxygenated. In addition, the right heart has to pump
at the same pressure as the left side. Several changes
follow. First, the baby turns blue (cyanotic) because of
the deoxygenated blood that bypasses the lungs.
Deoxygenated blood is darker and appears blue
through the skin. Second, the right side of the heart
(ventricle) hypertrophies (gets more muscular) from
the extra exercise demanded of it. Next, the low oxygen causes the blood to get thicker and clot more
easily. Clots in the veins can now pass through the
hole in the heart and directly enter the aorta, where
they can do much more damage than in the lungs–such
3659

Thalassemia

KEY TERMS
Aorta—Main arterial trunk that moves blood from
the heart to the arteries, which transport the blood
throughout the body.
Cyanosis—Blue-colored skin due to oxygen-deficient blood.
Endocarditis—Inflammation of the lining of the heart.
Infarct—Death of tissue due to shutting off the
blood supply.
Septicemia—Blood poisoning.
Systemic circulation—Through the body, asopposed
to ‘‘pulmonary’’–through the lungs.
Ventricles—The muscular chambers of the heart
that do the pumping.

infant, and the size of the various defects. There are
temporary surgical procedures that can prolong the
time before corrective surgery while the baby grows
larger and stronger.
During surgery, the pulmonary valve is widened,
the ventricular septal defect is closed, and any interim
corrections removed.

Prognosis
Surgical correction has a high rate of success,
returning the child to near–normal health.
Resources
BOOKS

Friedman, William F., and John S. Child. ‘‘Congenital
Heart Disease in the Adult.’’ In Harrison’s
Principles of Internal Medicine, edited by Anthony
S. Fauci, et al. New York: McGraw-Hill, 1997.

J. Ricker Polsdorfer, MD

as causing infarcts in the brain. In addition, these
anomalies make the lining of the heart more susceptible to infection–endocarditis– which can damage
valves and lead to blood poisoning (septicemia).

Causes and symptoms
Tetralogy of Fallot is a congenital defect with
unknown causes.
Babies with tetralogy of Fallot are blue at birth
(cyanosis). Sometimes the blue color appears only
when they cry. They also have detectable heart murmurs. Infants with mild forms can have surgery postponed until they are older. Infants with more severe
symptoms often have attacks of worsened cyanosis.
During attacks, they turn very blue, have shortness of
breath, and can faint. This usually occurs during
heightened activity, such as crying.

Diagnosis
A complete evaluation of the circulation is
required, including testing the blood for its oxygen
content; ultrasound; and x rays of the heart accompanied by a contrast agent to determine the amount of
blood flowing in the wrong direction. A search for
other birth defects is also necessary, because they
tend to happen together.

Thalassemia
Definition
Thalassemia describes a group of inherited disorders characterized by reduced or absent amounts of
hemoglobin, the oxygen-carrying protein inside the
red blood cells. There are two basic groups of thalassemia disorders: alpha thalassemia and beta thalassemia. These conditions cause varying degrees of
anemia, which can range from insignificant to life
threatening.

Description
All types of thalassemias are considered quantitative diseases of hemoglobin, because the quantity of
hemoglobin produced is reduced or absent. Usual
adult hemoglobin is made up of three components:
alpha globin, beta globin, and heme. Thalassemias
are classified according to the globin that is affected,
hence the names alpha and beta thalassemia. Although
both classes of thalassemia affect the same protein, the
alpha and beta thalassemias are distinct diseases that
affect the body in different ways.

Treatment
Correction of the defects are done through surgery. Surgery must be carefully timed with attention to
the progression of the disease process, the size of the
3660

Beta thalassemia
Beta thalassemia may be the most best-known
type of thalassemia and is also called Cooley’s anemia.
GALE ENCYCLOPEDIA OF MEDICINE

Alpha thalassemia
Alpha thalassemia is the result of changes in the
genes for the alpha globin component of hemoglobin.
There are two main types of alpha thalassemia disease:
hemoglobin H disease and alpha thalassemia major.
The two diseases are quite different from beta thalassemia as well as from one another. Individuals with
hemoglobin H disease can experience events of hemolytic anemia—anemia caused by the rapid breakdown
of the red blood cells. These events are thought to be
triggered by various environmental causes, such as
infection and/or exposure to certain chemicals.
Hemoglobin H disease is in most cases milder than
beta thalassemia. It does not generally require transfusion therapy. Alpha thalassemia major is a very serious
disease that results in severe anemia that begins even
before birth. Most affected babies do not survive to be
born or die shortly after birth.
The thalassemias are among the most common
genetic diseases worldwide. Both alpha and beta thalassemia have been described in individuals of almost
every ancestry, but the conditions are more common
among certain ethnic groups. Unaffected carriers of all
types of thalassemia traits do not experience health
problems. In fact, the thalassemia trait is protective
GALE ENCYCLOPEDIA OF MEDICINE

against malaria, a disease caused by blood-borne parasites transmitted through mosquito bites. According
to a widely accepted theory, most genetic changes—
mutations—that cause thalassemia occurred multiple
generations ago. Coincidentally, these mutations
increased the likelihood that carriers would survive
malaria infection. Survivors passed the mutation
onto their offspring, and the trait became established
throughout areas where malaria is common. As populations migrated, so did the thalassemia traits.
Beta thalassemia trait is seen most commonly in
people with the following ancestry: Mediterranean
(including North African, and particularly Italian
and Greek), Middle Eastern, Indian, African,
Chinese, and Southeast Asian (including Vietnamese,
Laotian, Thai, Singaporean, Filipino, Cambodian,
Malaysian, Burmese, and Indonesian). Alpha-thalassemia trait is seen with increased frequency in the same
ethnic groups. However, there are different types of
alpha thalassemia traits within these populations. The
frequency of hemoglobin H disease and alpha thalassemia major depends on the type of alpha thalassemia
trait. The populations in which alpha thalassemia diseases are most common include Southeast Asians and
Chinese (particularly Southern Chinese).
It is difficult to obtain accurate prevalence figures
for various types of thalassemia within different populations. This difficulty arises due to testing limitations
in determining exact genetic diagnoses, as well as the
fact that many studies have focused on small, biased
hospital populations.
Two studies reflect prevalence figures that can be
helpful counseling families and determining who to
screen for beta thalassemia. Between the years of
1990 and 1996, the State of California screened more
than 3.1 million infants born in the state for beta
thalassemia. Approximately 1 in 114,000 infants had
beta thalassemia major, with prevalence rates being
highest among Asian Indians (about one in 4,000),
Southeast Asians (about one in 10,000), and Middle
Easterners (about one in 7,000). Another type of beta
thalassemia disease, E/beta thalassemia, was represented in approximately one in 110,000 births, all of
which occurred in families of Southeast Asian ancestry. Among Southeast Asians, the prevalence of E/
beta thalassemia was approximately one in 2,600
births. This is in keeping with the observation that
hemoglobin E trait carrier rates are relatively high
within the Southeast Asian population: 16% in a
study of 768 immigrants to California, and up to
25% in some specific Southeast Asian populations
such as Cambodians. While these California studies
address some of the limitations of earlier population
3661

Thalassemia

It is caused by a change in the gene for the beta globin
component of hemoglobin. Beta thalassemia causes
variable anemia that can range from moderate to
severe, depending in part on the exact genetic change
underlying the disease. Beta thalassemia can be classified based on clinical symptoms. Beta thalassemia
major usually causes severe anemia that can occur
within months after birth. If left untreated, severe
anemia can result in insufficient growth and development, as well as other common physical complications
that can lead to a dramatically decreased life-expectancy. Fortunately, in developed countries beta thalassemia is usually identified by screening in the
newborn period, before symptoms have developed.
Children who are identified early can be started on
ongoing blood transfusion therapy as needed.
Although transfusion therapy prevents many of the
complications of severe anemia, the body is unable to
eliminate the excess iron contained in the transfused
blood. Over time, the excess iron deposits in tissues
and organs, resulting in damage and organ failure.
Another medication must be administered to help the
body eliminate the excess iron and prevent iron-overload complications. Beta thalassemia intermedia
describes the disease in individuals who have moderate
anemia that only requires blood transfusions intermittently, if at all.

Thalassemia

studies, the pattern observed in California is expected
to be different in other areas of the United States and
the world. For example, Italians are underrepresented
in this population when compared to the population
of the East Coast of the United States.

have been described that cause beta thalassemia,
designated as either beta0 or beta+ mutations. No
beta globin is produced with a beta0 mutation, and
only a small fraction of the normal amount of beta
globin is produced with a beta+ mutation.

Determining prevalence figures for alpha thalassemia is even more difficult due to increased limitations in diagnostic testing. All types of alpha
thalassemia disease are most common among people
of Southeast Asian and Chinese descent, for reasons
that become clearer with an understanding of the
underlying genetics of alpha thalassemia. One study
of 500 pregnant women in Northern Thailand estimated a frequency of one in 500 pregnancies affected
by alpha thalassemia major, for example. Prevalence
of alpha thalassemia disease is significantly lower in
the United States primarily because of immigration
patterns; although at least one state, California, has
observed growing hemoglobin H disease incidence
rates that are high enough to justify universal newborn
screening for the condition.

When an individual has one normal beta globin
gene and one with a beta thalassemia mutation, he or
she is said to carry the beta thalassemia trait. Beta
thalassemia trait, like other hemoglobin traits, is protective against malaria infection. Trait status is generally thought not to cause health problems, although
some women with beta thalassemia trait may have an
increased tendency toward anemia during pregnancy.

Causes
Genetics
Humans normally make several types of the oxygen-carrying protein hemoglobin. An individual’s
stage in development determines whether he or she
makes primarily embryonic, fetal, or adult hemoglobins. All types of hemoglobin are made of three components: heme, alpha (or alpha-like) globin, and beta
(or beta-like) globin. All types of thalassemia are
caused by changes in either the alpha- or beta-globin
gene. These changes cause little or no globin to be
produced. The thalassemias are, therefore, considered
quantitative hemoglobin diseases. All types of thalassemias are recessively inherited, meaning that a genetic
change must be inherited from both the mother and
the father. The severity of the disease is influenced by
the exact thalassemia mutations inherited, as well as
other genetic and environmental factors. There are
rare exceptions, notably with beta thalassemia, where
globin gene mutations exhibit a dominant pattern of
inheritance in which only one gene needs to be altered
in order to see disease expression. Scientists continue
to study the causes. For instance, a new mutation for
alpha-thalassemia was discovered for the first time
among Iranian patients in 2004.
BETA-THALASSEMIA. Most individuals have two
normal copies of the beta globin gene, which is located
on chromosome 11 and makes the beta globin component of normal adult hemoglobin, hemoglobin A.
There are approximately 100 genetic mutations that

3662

When two members of a couple carry the beta
thalassemia trait, there is a 25% chance that each of
their children will inherit beta thalassemia disease by
inheriting two beta thalassemia mutations, one from
each parent. The clinical severity of the beta thalassemia disease—whether an individual has beta thalassemia intermedia or beta thalassemia major—will
depend largely on whether the mutations inherited
are beta0 thalassemia or beta+ thalassemia mutations. Two beta0 mutations generally lead to beta
thalassemia major, and two beta+ thalassemia mutations generally lead to beta thalassemia intermedia.
Inheritance of one beta0 and one beta+ thalassemia
mutation tends to be less predictable.
Although relatively uncommon, there are other
thalassemia-like mutations that can affect the beta
globin gene. Hemoglobin E is the result of a substitution of a single nucleotide. This change results in a
structurally altered hemoglobin that is produced in
decreased amounts. Therefore, hemoglobin E is
unique in that it is both a quantitative (i.e. thalassemia-like) and qualitative trait. When co-inherited with
a beta thalassemia trait, it causes a disease that is
almost indistinguishable from beta thalassemia disease. Large deletions around and including the beta
globin gene can lead to delta/beta thalassemia or hereditary persistence of fetal hemoglobin (HPFH).
Interestingly, delta/beta thalassemia trait behaves
very similarly to beta thalassemia trait in its clinical
manifestations. However, HPFH trait does not tend to
cause hemoglobin disease when co-inherited with a
second thalassemia or other beta globin mutation.
ALPHA-THALASSEMIA. Most individuals have four
normal copies of the alpha globin gene, two copies on
each chromosome 16. These genes make the alpha
globin component of normal adult hemoglobin,
which is called hemoglobin A. Alpha globin is also a
component of fetal hemoglobin and the other major
adult hemoglobin called hemoglobin A2. Mutations

GALE ENCYCLOPEDIA OF MEDICINE

Absence of one alpha globin gene leads to a condition known as silent alpha thalassemia trait. This
condition causes no health problems and can be
detected only by special genetic testing. Alpha thalassemia trait occurs when two alpha globin genes are
missing. This can occur in two ways. The genes may be
deleted from the same chromosome, causing the ‘cis’
type of alpha thalassemia trait. Alternately, they may
be deleted from different chromosomes, causing the
‘trans’ type of alpha thalassemia trait. In both
instances, there are no associated health problems,
although the trait status may be detected by more
routine blood screening.
Hemoglobin H disease results from the deletion of
three alpha globin genes, such that there is only one
functioning gene. Typically, this can occur when one
parent carries the silent alpha thalassemia trait, and the
other parent carries the ‘cis’ type of the alpha thalassemia
trait. In this situation, there is a 25% chance for hemoglobin H disease in each of such a couple’s children.
Hemoglobin H disease-like symptoms can also be a
part of a unique condition called alpha thalassemia
mental retardation syndrome. Alpha thalassemia mental
retardation syndrome can be caused by a deletion of a
significant amount of chromosome 16, affecting the
alpha globin genes. This is usually not inherited, but
rather occurs sporadically in the affected individual.
Affected individuals have mild hemoglobin H disease,
mild-to-moderate mental retardation, and characteristic facial features. This syndrome can also occur as a
sex-linked form in which a mutation is inherited in a
particular gene on the X-chromosome. This gene influences alpha globin production, as well as various other
developmental processes. Individuals affected with this
form of the syndrome tend to have more severe mental
retardation, delayed development, nearly absent
speech, characteristic facial features, and genital-urinary abnormalities. The remaining discussion will focus
only on aspects of hemoglobin H disease.
Alpha thalassemia major results from the deletion
of all four alpha globin genes, such that there are no
functioning alpha globin genes. This can occur when
both parents carry the ‘cis’ type of the alpha thalassemia trait. In this situation, there is a 25% chance for
alpha thalassemia major in each of such a couple’s
children.
GALE ENCYCLOPEDIA OF MEDICINE

Symptoms
Beta thalassemia
Beta thalassemia major is characterized by severe
anemia that can begin months after birth. In the
United States and other developed countries beta thalassemia is identified and treated early and effectively.
Therefore, the following discussion of symptoms
applies primarily to affected individuals in the past
and unfortunately in some underdeveloped countries
now. If untreated, beta thalassemia major can lead to
severe lethargy, paleness, and delays in growth and
development. The body attempts to compensate by
producing more blood, which is made inside the
bones in the marrow. However, this is ineffective without the needed genetic instructions to make enough
functioning hemoglobin. Instead, obvious bone
expansion and changes occur that cause characteristic
facial and other changes in appearance, as well as
increased risk of fractures. Severe anemia taxes other
organs in the body—such as the heart, spleen, and
liver—which must work harder than usual. This can
lead to heart failure, as well as enlargement and other
problems of the liver and spleen. When untreated, beta
thalassemia major generally results in childhood
death, usually due to heart failure. In 2004, the first
known heart attack associated with beta thalassemia
major was reported. Fortunately, in developed countries diagnosis is usually made early, often before
symptoms have begun. This allows for treatment
with blood transfusion therapy, which can prevent
most of the complications of the severe anemia caused
by beta thalassemia major. Individuals with beta thalassemia intermedia have a more moderate anemia
that may only require treatment with transfusion
intermittently, such as when infections occur and
stress the body. As a person with beta thalassemia
intermedia gets older, however, the need for blood
transfusions may increase to the point that they are
required on a regular basis. When this occurs their
disease becomes more similar to beta thalassemia
major. Other genetic and environmental factors can
influence the course of the disease as well. For example, co-inheritance of one or two alpha thalassemia
mutations can tend to ameliorate some of the symptoms of beta thalassemia disease, which result in part
from an imbalance in the amount of alpha- and betaglobin present in the red blood cells.
Hemoglobin H disease
Absence of three alpha globin genes causes an
imbalance of alpha and beta globin proteins in the red
blood cells. The excess beta globin proteins tend to
3663

Thalassemia

of the alpha globin genes are usually deletions of the
gene, resulting in absent production of alpha globin.
Since there are four genes (instead of the usual two) to
consider when looking at alpha globin gene inheritance, there are several alpha globin types that are
possible.

Thalassemia

come together to form hemoglobin H, which is unable
to release oxygen to the tissues. In addition, hemoglobin H tends to precipitate out in the cells, causing
damage to the red blood cell membrane. When affected
individuals are exposed to certain drugs and chemicals
known to make the membrane more fragile, the cells are
thought to become vulnerable to breakdown in large
numbers, a complication called hemolytic anemia. Fever
and infection are also considered to be triggers of hemolytic anemia in hemoglobin H disease. This can result in
fatigue, paleness, and a yellow discoloration of the skin
and whites of eyes called jaundice. Usually, the anemia
is mild enough not to require treatment. Severe anemia
events may require blood transfusion, however, and are
usually accompanied by such other symptoms as dark
feces or urine and abdominal or back pain. These events
are uncommon in hemoglobin H disease, although they
occur more frequently in a more serious type of hemoglobin H disease called hemoglobin H/Constant Spring
disease. Individuals effected with this type of hemoglobin H disease are also more likely to have enlargement
of and other problems with the spleen.
Alpha thalassemia major
Because alpha globin is a necessary component of
all major hemoglobins and some minor hemoglobins,
absence of all functioning alpha globin genes leads to
serious medical consequences that begin even before
birth. Affected fetuses develop severe anemia as early
as the first trimester of pregnancy. The placenta, heart,
liver, spleen, and adrenal glands may all become
enlarged. Fluid can begin collecting throughout the
body as early as the start of the second trimester,
causing damage to developing tissues and organs.
Growth retardation is also common. Affected fetuses
usually miscarry or die shortly after birth. In addition,
women carrying affected fetuses are at increased risk
of developing complications of pregnancy and delivery. Up to 80% of such women develop toxemia, a
disturbance of metabolism that can potentially lead to
convulsions and coma. Other maternal complications
include premature delivery and increased rates of
delivery by cesarean section, as well as hemorrhage
after delivery.

Diagnosis
Thalassemia may be suspected if an individual
shows signs that are suggestive of the disease. In all
cases, however, laboratory diagnosis is essential to
confirm the exact diagnosis and to allow for the provision of accurate genetic counseling about recurrence
risks and testing options for parents and affected
3664

individuals. Screening is likewise recommended to
determine trait status for individuals of high-risk ethnic groups.
The following tests are used to screen for thalassemia disease and/or trait:


complete blood count



hemoglobin electrophoresis with quantitative hemoglobin A2 and hemoglobin F



free erythrocyte-protoporphyrin (or ferritin or other
studies of serum iron levels)

A complete blood count will identify low levels of
hemoglobin, small red blood cells, and other red blood
cell abnormalities that are characteristic of a thalassemia diagnosis. Since thalassemia trait can sometimes
be difficult to distinguish from iron deficiency, tests to
evaluate iron levels are important. A hemoglobin electrophoresis is a test that can help identify the types and
quantities of hemoglobin made by an individual. This
test uses an electric field applied across a slab of gellike material. Hemoglobins migrate through this gel at
various rates and to specific locations, depending on
their size, shape, and electrical charge. Isoelectric
focusing and high-performance liquid chromatography
(HPLC) use similar principles to separate hemoglobins and can be used instead of or in various combinations with hemoglobin electrophoresis to determine
the types and quantities of hemoglobin present.
Hemoglobin electrophoresis results are usually within
the normal range for all types of alpha thalassemia.
However, hemoglobin A2 levels and sometimes hemoglobin F levels are elevated when beta thalassemia
disease or trait is present. Hemoglobin electrophoresis
can also detect structurally abnormal hemoglobins
that may be co-inherited with a thalassemia trait to
cause thalassemia disease (i.e., hemoglobin E) or other
types of hemoglobin disease (i.e., sickle hemoglobin).
Sometimes DNA testing is needed in addition to the
above screening tests. This can be performed to help
confirm the diagnosis and establish the exact genetic
type of thalassemia.
Diagnosis of thalassemia can occur under various
circumstances and at various ages. Several states offer
thalassemia screening as part of the usual battery of
blood tests done for newborns. This allows for early
identification and treatment. Thalassemia can be identified before birth through the use of prenatal diagnosis.
Chorionic villus sampling (CVS) can be offered as early
as 10 weeks of pregnancy and involves removing a
sample of the placenta made by the baby and testing
the cells. CVS carries a risk of causing a miscarriage that
is between 0.5%-1%. Amniocentesis is generally offered
between 15 and 22 weeks of pregnancy, but can
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Beta Thalassemia
Individuals with beta thalassemia major receive regular blood transfusions, usually on a monthly basis. This
helps prevent severe anemia and allows for more normal
growth and development. Transfusion therapy does
have limitations, however. Individuals can develop reactions to certain proteins in the blood—called a transfusion reaction. This can make locating appropriately
matched donor blood more difficult. Although blood
supplies in the United States are very safe, particularly
relative to the past and to other areas of the world, there
remains an increased risk of exposure to such bloodborne infections as hepatitis. Additionally, the body is
not able to get rid of the excess iron that accompanies
each transfusion. An additional medication called desferoxamine is administered, usually five nights per week
over a period of several hours, using an automatic pump
that can be used during sleep or taken anywhere the
person goes. This medication is able to bind to the excess
iron, which can then be eliminated through urine. If
desferoxamine is not used regularly or is unavailable,
iron overload can develop and cause tissue damage and
organ damage and failure. The heart, liver, and endocrine organs are particularly vulnerable. Desferoxamine
itself may rarely produce allergic or toxic side effects,
including hearing damage. Signs of desferoxamine toxicity are screened for and generally develop in individuals
who overuse the medication when body iron levels are
sufficiently low. Overall, however, transfusion and desferoxamine therapy have increased the life expectancy of
individuals with the most severe types of beta thalassemia major to the 4th or 5th decade. This can be expected
to improve with time and increased developments in
treatment, as well as for those with more mild forms of
the disease.
GALE ENCYCLOPEDIA OF MEDICINE

New treatments offer additional options for some
individuals with beta thalassemia major. There are
various medications that target the production of red
blood cells (i.e. erythropoeitin) or fetal hemoglobin
(i.e. hydroxyurea and butyrate). Their effectiveness
in ameliorating the severity of beta thalassemia is
currently being investigated. Another promising new
treatment is bone marrow transplantation, in which the
bone marrow of an affected individual is replaced with
the bone marrow of an unaffected donor. If successful,
this treatment can provide a cure. However, there is an
approximately 10-15% chance the procedure could be
unsuccessful (i.e. the thalassemia returns); result in
complications (i.e. graft-versus-host disease); or result
in death. The risk for specific individuals depends on
current health status, age, and other factors. Because
of the risks involved and the fact that beta thalassemia
is a treatable condition, transplant physicians require
a brother or sister donor who has an identically
matched tissue type, called HLA type. HLA type
refers to the unique set of proteins present on each
individual’s cells, which allows the immune system to
recognize ‘‘self ’’ from ‘‘foreign.’’ HLA type is genetically determined, so there is a 25% chance for two
siblings to be a match. Transplant physicians and
researchers are also investigating ways to improve
the safety and effectiveness of bone marrow transplantation. Using newborn sibling umbilical cord blood—
the blood from the placenta that is otherwise discarded after birth but contains cells that can go on to
make bone marrow—seems to provide a safer and
perhaps more effective source of donor cells. Donors
and recipients may not have to be perfect HLA
matches for a successful transplant using cord blood
cells. Trials are also underway to determine the effectiveness of ‘‘partial transplants,’’ in which a safer
transplant procedure is used to replace only a percentage of the affected individual’s bone marrow. Other
possible treatments on the horizon may include gene
therapy techniques aimed at increasing the amount of
normal hemoglobin the body is able to make.
Hemoglobin H disease
Hemoglobin H disease is a relatively mild form of
thalassemia that may go unrecognized. It is not generally considered a condition that will reduce one’s life
expectancy. Education is an important part of managing the health of an individual with hemoglobin H
disease. It is important to be able to recognize the signs
of severe anemia that require medical attention. It is
also important to be aware of the medications, chemicals, and other exposures to avoid due to the theoretical risk they pose of causing a severe anemia event.
3665

Thalassemia

sometimes be offered earlier. Two to three tablespoons
of the fluid surrounding the baby is removed. This fluid
contains fetal cells that can be tested. The risk of miscarriage associated with amniocentesis ranges from
0.33–0.5%. Pregnant woman and couples may choose
prenatal testing in order to prepare for the birth of a
baby that may have thalassemia. Alternately, knowing
the diagnosis during pregnancy allows for the option of
pregnancy termination. Preimplantation genetic diagnosis (PGD) is a relatively new technique that involves
in-vitro fertilization followed by genetic testing of one
cell from each developing embryo. Only the embryos
unaffected by sickle cell disease are transferred back
into the uterus. PGD is currently available on a
research basis only and is relatively expensive.

Thalassemia

KEY TERMS
Anemia—A blood condition in which the level of
hemoglobin or the number of red blood cells falls
below normal values. Common symptoms include
paleness, fatigue, and shortness of breath.
Bilirubin—A yellow pigment that is the end result of
hemoglobin breakdown. This pigment is metabolized in the liver and excreted from the body through
the bile. Bloodstream levels are normally low; however, extensive red cell destruction leads to excessive bilirubin formation and jaundice.
Bone marrow—A spongy tissue located in the hollow centers of certain bones, such as the skull and
hip bones. Bone marrow is the site of blood cell
generation.
Bone marrow transplantation—A medical procedure used to treat some diseases that arise from
defective blood cell formation in the bone marrow.
Healthy bone marrow is extracted from a donor to
replace the marrow in an ailing individual. Proteins
on the surface of bone marrow cells must be identical or very closely matched between a donor and the
recipient.
Desferoxamine—The primary drug used in iron chelation therapy. It aids in counteracting the life-threatening buildup of iron in the body associated with
long-term blood transfusions.
Globin—One of the component protein molecules
found in hemoglobin. Normal adult hemoglobin
has a pair each of alpha-globin and beta-globin
molecules.
Heme—The iron-containing molecule in hemoglobin that serves as the site for oxygen binding.
Hemoglobin—Protein-iron compound in the blood
that carries oxygen to the cells and carries carbon
dioxide away from the cells.
Hemoglobin A—Normal adult hemoglobin that contains a heme molecule, two alpha-globin molecules,
and two beta-globin molecules.

When severe anemia occurs, it is treated with blood
transfusion therapy. For individuals with hemoglobin
H disease, this is rarely required. For those with the
hemoglobin H/Constant Spring form of the disease,
the need for transfusions may be intermittent or
ongoing, perhaps on a monthly basis and requiring
desferoxamine treatment. Individuals with this more
severe form of the disease may also have an increased
3666

Hemoglobin electrophoresis—A laboratory test that
separates molecules based on their size, shape, or
electrical charge.
Hepatomegaly—An abnormally large liver.
HLA type—Refers to the unique set of proteins called
human leukocyte antigens. These proteins are present
on each individual’s cell and allow the immune system
to recognize ‘self’ from ‘foreign’. HLA type is particularly important in organ and tissue transplantation.
Hydroxyurea—A drug that has been shown to induce
production of fetal hemoglobin. Fetal hemoglobin has
a pair of gamma-globin molecules in place of the
typical beta-globins of adult hemoglobin. Higherthan-normal levels of fetal hemoglobin can ameliorate some of the symptoms of thalassemia.
Iron overload—A side effect of frequent blood transfusions in which the body accumulates abnormally
high levels of iron. Iron deposits can form in organs,
particularly the heart, and cause life-threatening
damage.
Jaundice—Yellowing of the skin or eyes due to
excess of bilirubin in the blood.
Mutation—A permanent change in the genetic
material that may alter a trait or characteristic of an
individual, or manifest as disease, and can be transmitted to offspring.
Placenta—The organ responsible for oxygen and
nutrition exchange between a pregnant mother and
her developing baby.
Red blood cell—Hemoglobin-containing blood cells
that transport oxygen from the lungs to tissues. In the
tissues, the red blood cells exchange their oxygen for
carbon dioxide, which is brought back to the lungs to
be exhaled.
Screening—Process through which carriers of a trait
may be identified within a population.
Splenomegaly—Enlargement of the spleen.

chance of requiring removal of an enlarged and/or
overactive spleen.
Alpha thalassemia major
Because alpha thalassemia major is most often
a condition that is fatal in the prenatal or newborn
period, treatment has previously been focused on
GALE ENCYCLOPEDIA OF MEDICINE

National Organization for Rare Disorders (NORD). PO
Box 8923, New Fairfield, CT 06812-8923. (203)
746-6518 or (800) 999-6673. Fax: (203) 746-6481.
http://www.rarediseases.org.
OTHER

Bojanowski J. ‘‘Alpha Thalassemia Major: The Possibility
of Long-Term Survival.’’ Pamphlet from the Northern
California Comprehensive Thalassemia Center. (1999).
Children’s Hospital Oakland, Northern California
Comprehensive Thalassemia Center website. <http://
www.thalassemia.com>.
Cooley’s Anemia Foundation, Inc. website. <http://
www.thalassemia.org/gohome.html>.
Joint Center for Sickle Cell and Thalassemic Disorders
website. <http://cancer.mgh.harvard.edu/medOnc/
sickle.htm>.

Jennifer Bojanowski, MS, CGC
Teresa G. Odle

Prognosis
As discussed above, the prognosis for individuals
with the most serious types of thalassemia has
improved drastically in the last several years following
recent medical advances in transfusion, chemo-, and
transplantation therapy. Advances continue and promise to improve the life expectancy and quality of life
further for affected individuals.

Thallium heart scan
Definition
A thallium heart scan is a test using a special
camera and a small amount of radioactive substance
injected into the bloodstream to make an image of the
blood flow to the heart.

Resources
PERIODICALS

‘‘First Known Heart Attack Associated With Betathalassemia Major Reported.’’ Heart Disease
Weekly February 22, 2004: 10.
‘‘Novel Alpha-thalassemia Mutations Identified.’’
Hematology Week January 26, 2004: 19.
ORGANIZATIONS

Children’s Blood Foundation. 333 East 38th St., Room 830,
New York, NY 10016-2745. (212) 297-4336.
cfg@nyh.med.cornell.edu.
Cooley’s Anemia Foundation, Inc. 129-09 26th Ave. #203,
Flushing, NY 11354. (800) 522-7222 or (718) 321-2873.
<http://www.thalassemia.org>.
March of Dimes Birth Defects Foundation. 1275
Mamaroneck Ave., White Plains, NY 10605. (888)
663-4637. resourcecenter@modimes.org. <http://
www.modimes.org>.
National Heart, Lung, and Blood Institute. PO Box 30105,
Bethseda, MD 20824-0105. (301) 592-8573.
nhlbiinfo@rover.nhlbi.nih.gov. <http://
www.nhlbi.nih.gov>.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
A thallium heart scan is used to evaluate the blood
supply to the heart muscle. It can identify areas of the
heart that may have a poor blood supply as a result of
damage from a previous heart attack or blocked coronary arteries. While exercise testing has long been a
standard examination in the diagnosis of coronary
artery disease, in some cases, the thallium scan may
be more sensitive and more specific in the information
it provides. In other words, the test may be better able
to detect a problem and to differentiate one condition
from another. A thallium heart scan may more accurately detect ischemic heart disease. This type of scan is
most likely to be helpful in cases in which the exercise
test is inconclusive, the patient cannot exercise adequately, or a quantitative evaluation of blood flow is
required. In addition to evaluating coronary artery
disease, thallium scanning can help to evaluate blood
flow following treatment of clogged arteries with
coronary artery bypass graft surgery or angioplasty.
3667

Thallium heart scan

identifying affected pregnancies in order to provide
appropriate management to reduce potential maternal
complications. Pregnancy termination provides one
form of management. Increased prenatal surveillance
and early treatment of maternal complications is an
approach that is appropriate for mothers who wish to
continue their pregnancy with the knowledge that the
baby will most likely not survive. In recent years, there
have been a handful of infants with this condition who
have survived long-term. Most of these infants received
experimental treatment including transfusions before
birth, early delivery, and even bone marrow transplantation before birth, although the latter procedure has
not yet been successful. For those infants that survive to
delivery, there seems to be an increased risk of developmental problems and physical effects, particularly heart
and genital malformations. Otherwise, their medical
outlook is similar to a child with beta thalassemia
major, with the important exception that ongoing, lifelong blood transfusions begin right at birth.

Thallium heart scan

Precautions
Radioisotopes such as thallium 201 should not be
administered during pregnancy because they may be
harmful to the fetus.

Description
The thallium scan is performed in conjunction
with an exercise stress test. At the end of the stress
test (once the patient has reached the highest level of
exercise he or she can comfortably achieve), a small
amount of the harmless radioisotope thallium 201 is
injected into the patient’s bloodstream through an
intravenous (IV) line. The patient then lies down
under a special camera called a gamma scintillation
camera, which makes photographs from the gamma
rays emitted by the thallium.
The thallium attaches itself to the red blood cells
and is carried throughout the body in the bloodstream. It enters the heart muscle by way of the
coronary arteries and collects in the cells of the
heart muscle that come into contact with the blood.
Since the thallium can reach only those areas of the
heart with an adequate blood supply, no thallium will
show up in poorly perfused areas of the heart (perfusion defects). These areas show up as ‘‘cold spots’’ on
the thallium scan. The patient may then be given a
second injection of thallium. Several hours later, the
gamma scintillation camera takes more pictures in
order to get an image of the heart when the patient
is at rest.
Cold spots that appear at rest as well as during
exercise often indicate areas where the heart tissue has
been damaged (for example, as a result of a prior heart
attack). Sometimes perfusion is adequate during rest
but cold spots appear during exercise, when the heart
has to work harder and has a greater demand for
blood. This can indicate some blockage in the coronary arteries, producing a condition called ischemia. In
ischemia, the heart temporarily does not get enough
blood flow. People with perfusion defects, especially
perfusion defects that appear only during exercise,
have the greatest risk of such future cardiac events as
heart attacks.
In recent years, there have been improvements in
heart scanning. Many centers now use a single
photon emission computed tomographic (SPECT)
camera, which provides a clearer image. Some centers also use a type of radioactive chemical called
sestamibi. Sestamibi is used along with a radioactive
compound called technetium. While thallium may
still be better for some uses, such as providing a
3668

A thallium scan showing many images of a human heart with
cold spots. (Custom Medical Stock Photo. Reproduced by
permission.)

better image of the heart muscle itself, sestamibi
may produce clearer images in overweight patients
and is more useful in assessing how well the heart
pumps blood.
If the patient is unable to exercise because of
another medical condition, such as arthritis, he or
she may be given a drug to mimic the effects of exercise
on the heart. Some of these drugs include dipyridamole (Persantine), which dilates the coronary arteries;
and dobutamine, which increases blood flow through
the heart muscle.

Preparation
Patients should not drink alcoholic or caffeinated
beverages, smoke tobacco, or ingest other nicotine
products for 24 hours before the test. These substances
can affect test results. Patients should also not eat
anything for at least three hours before the test. They
may also be instructed to stop taking certain medications during the test that may interfere with test
results.

Aftercare
In some cases, another set of scans may be needed,
and the patient may be given special instructions
regarding eating and test preparation. Otherwise, the
GALE ENCYCLOPEDIA OF MEDICINE

Angioplasty—The reconstruction of damaged blood
vessels.
Coronary bypass surgery—Surgery in which a section of blood vessel is used to bypass a blocked
coronary artery and restore an adequate blood supply to the heart muscle.
Perfusion—The passage of fluid (such as blood)
through a specific organ or area of the body (such
as the heart).
Radioisotope—A radioactive form of a chemical
element, which is used in medicine for therapeutic
or diagnostic purposes.

patient is free to return to his or her normal daily
activities.

Thematic apperception test
Definition
The thematic apperception test (TAT) is a projective personality test that was designed at Harvard in
the 1930s by Christiana D. Morgan and Henry A.
Murray. Along with the MMPI and the Rorschach,
the TAT is one of the most widely used psychological
tests. A projective test is one in which a person’s patterns of thought, attitudes, observational capacity, and
emotional responses are evaluated on the basis of
responses to ambiguous test materials. The TAT consists of 31 pictures that depict a variety of social and
interpersonal situations.The subject is asked to tell a
story about each picture to the examiner. Of the 31
pictures, 10 are gender-specific while 21 others can
be used with adults of either sex and with children. As
of 2001, the TAT is distributed by Harcourt Brace
Educational Measurement.

Purpose

Risks
Radioisotopes such as thallium 201 should not be
administered during pregnancy because they may be
harmful to the fetus.

Normal results
A normal thallium scan shows healthy blood flow
through the coronary arteries and normal perfusion of
the heart muscle, without cold spots, both at rest and
during exercise.

Abnormal results
Cold spots on the scan, where no thallium shows
up, indicate areas of the heart that are not getting an
adequate supply of blood. Cold spots appearing both at
rest and during exercise may indicate areas where the
heart tissue has been damaged. However, ‘‘reversible’’
cold spots appearing only during exercise usually indicate some blockage of the coronary arteries.
Resources
ORGANIZATION

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-630 or (800) 242-8721. inquire@
heart.org. <http://www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Robert Scott Dinsmoor
GALE ENCYCLOPEDIA OF MEDICINE

The original purpose of the TAT was to reveal
the underlying dynamics of the subject’s personality, such as internal conflicts, dominant drives and
interests, motives, etc. The specific motives that the
TAT assesses include the need for achievement,
need for power, the need for intimacy, and problem-solving abilities. After World War II, however, the TAT was used by psychoanalysts and
clinicians from other schools of thought to evaluate emotionally disturbed patients. Another shift
took place in the 1970s, when the influence of the
human potential movement led many psychologists
to emphasize the usefulness of the TAT in assessment services—that is, using the test to help clients
understand themselves better and stimulate their
personal growth.
The TAT is widely used to research certain topics
in psychology, such as dreams and fantasies, mate
selection, the factors that motivate people’s choice of
occupations, and similar subjects. It is sometimes used
in psychiatric evaluations to assess disordered thinking and in forensic examinations to evaluate crime
suspects, even though it is not a diagnostic test. As
mentioned earlier, the TAT can be used to help people
understand their own personality in greater depth and
build on that knowledge in making important life
decisions. Lastly, it is sometimes used as a screener in
psychological evaluations of candidates for high-stress
occupations (law enforcement, the military, religious
ministry, etc.).
3669

Thematic apperception test

KEY TERMS

Therapeutic baths

Normal results

KEY TERMS
Apperception—The process of understanding
through linkage with previous experience.
Human potential movement—A movement in psychotherapy that began in the 1960s and emphasized maximizing the potential of each participant
through such techniques as group therapy and sensitivity training.
Projective test—A type of psychological test that
assesses a person’s thinking patterns, observational
ability, feelings, and attitudes on the basis of
responses to ambiguous test materials. It is not
intended to diagnose psychiatric disorders.

Since the TAT is used primarily for personality
assessment rather than diagnosis of mental disorders,
it does not yield a ‘‘score’’ in the usual sense.
Resources
BOOKS

Geiser, Lon, and Morris I. Stein. Evocative Images: The
Thematic Apperception Test and the Art of Projection.
Washington, DC: American Psychological Association,
1999.

Rebecca J. Frey, PhD

Therapeutic abortion see Abortion,
therapeutic

Precautions
The TAT has been criticized for its lack of a standardized method of administration as well as the lack of
standard norms for interpretation. Studies of the interactions between examiners and test subjects have found
that the race, sex, and social class of both participants
influence both the stories that are told and the way the
stories are interpreted by the examiner. Attempts have
been made to design sets of TAT cards for African
American and for elderly test subjects, but the results
have not been encouraging. In addition, the 31 standard pictures have been criticized for being too gloomy
or depressing, and therefore limiting the range of personality characteristics that the test can assess.

Description
There is no standardized procedure or set of cards
for administering the TAT, except that it is a one-onone test. It cannot be administered to groups. In one
common method of administration, the examiner
shows the subject only 10 of the 31 cards at each of
two sessions. The sessions are not timed, but average
about an hour in length.

Preparation
There is no specific preparation necessary before
taking the TAT, although most examiners prefer to schedule sessions (if there is more than one) over two days.

Therapeutic baths
Definition
Bathing the skin in a variety of preparations in
order to remove crusts, scales, and old medications or
to relieve inflammation and itching is called a therapeutic bath.

Purpose
Baths or soaks (balneotherapy) are an easy way
to treat a variety of skin disorders involving large areas
of the skin. They relieve general aches and pains and
can ease dry or oily, inflamed or itchy skin. Hot baths
are relaxing and stimulating; cool baths can reduce
inflammation.
Therapeutic baths are useful for itchy skin, hives,
sunburn, chafing, poison ivy and oak, eczema, skin
irritation, and dry skin. They may also help to relieve
emotional tension and stress. Brief therapeutic baths
may be useful in preventing pressure ulcers and other
skin problems in the elderly.
Many family care physicians recommend
warm-water therapeutic baths as a way to relieve
labor pains during childbirth without administering
drugs.

Precautions
Risks
The chief risks involved in taking the TAT are a
bad ‘‘fit’’ between the examiner and the test subject,
and misuse of the results.
3670

The temperature of the water should be comfortable. The bath should not last longer than 20–30
minutes because of the tendency of these soaks to
soften and wear away the skin.
GALE ENCYCLOPEDIA OF MEDICINE

Eczema—An inflammation of the skin that
usually itches and sometimes forms scales or
blisters.

A bath mat should be used, since medications may
cause the floor of the tub to be slippery.
Eczema and other skin diseases can be treated
with an ointment that contains a derivative of coal
tar. Parts of the coal tar are volatile, so the bathroom
should be well ventilated.

Description
The tub should be filled half–full with water at a
comfortable temperature. The water should not be
allowed to cool too much. If an emollient action
is needed, the patient should apply a lubricating
agent to the skin after the bath, since this increases
hydration.

BOOKS

Pelletier, Dr. Kenneth R. The Best Alternative Medicine,
Part I: Naturopathic Medicine. New York: Simon and
Schuster, 2002.
PERIODICALS

Hunter, S., J. Anderson, D. Hanson, et al. ‘‘Clinical Trial of
a Prevention and Treatment Protocol for Skin
Breakdown in Two Nursing Homes.’’ Journal of
Wound, Ostomy, and Continence Nursing 30 (September
2003): 250–258.
Keegan, L. ‘‘Therapies to Reduce Stress and Anxiety.’’
Critical Care Nursing Clinics of North America 15
(September 2003): 321–327.
Leeman, L., P. Fontaine, V. King, et al. ‘‘The Nature and
Management of Labor Pain: Part I. Nonpharmacologic
Pain Relief.’’ American Family Physician 68 (September
15, 2003): 1109–1112.
ORGANIZATIONS

The American Association of Naturopathic Physicians. 8201
Greensboro Drive, Suite 300, McLean, Virginia 22102.
(206) 298-0126. <http://naturopathic.org>.
Canadian Naturopathic Association/Association canadienne de naturopathie. 1255 Sheppard Avenue East at
Leslie, North York, ON M2K 1E2. (800) 551-4381 or
(416) 496-8633. <http://www.naturopathicassoc.ca>.

Different types of therapeutic baths are used for
different conditions:




colloidal oatmeal (oatmeal that has been ground into
a fine powder, e.g. Aveeno) coats, soothes, stops itch
and doesn’t dry out the skin
potassium permanganate—a dark purple salt—
makes a good disinfectant



bath oils are used as an emollient to ease itchy skin
and eczema



cornstarch is a soothing, drying bath for itchy skin



sodium bicarbonate can be cooling for hot, dry skin
conditions



saline (salt) water baths are used to treat lesions
scattered over the body

Preparation
Keep the room warm to minimize temperature
fluctuations. This precaution is particularly important
when bathing elderly patients.

Aftercare
After the bath, the skin should be blotted (not
rubbed) carefully with a towel. The patient should
wear loose, light clothing after the bath.
GALE ENCYCLOPEDIA OF MEDICINE

Carol A. Turkington
Rebecca J. Frey, PhD

Therapeutic drug monitoring see Drug therapy monitoring
Therapeutic massage see Massage

Therapeutic touch
Definition
Therapeutic touch, or TT, is a noninvasive
method of healing that was derived from an ancient
laying–on of hands technique. In TT, the practitioner
alters the patient’s energy field through an energy
transfer that moves from the hands of the practitioner
to the patient.

Origins
Therapeutic touch was developed in 1972 by Dora
Kunz, a psychic healer, and Dolores Krieger, Ph.D.,
R.N, a nurse and professor of nursing at New York
University. The year before, in 1971, when Krieger
was working as a registered nurse in a hospital, she
3671

Therapeutic touch

Resources

KEY TERMS

Therapeutic touch

became very frustrated when one of her patients, a
30-year-old female, lay dying from a gallbladder condition. In desperation, she tried what she was learning
from Kunz. Within one treatment, the patient’s
condition began to shift and she lived, surprising the
other hospital staff. Krieger and Kunz met during
the study of Oskar Estebany, a world–renowned
healer. They had invited Estebany to form a study
for three years, observing his work with patients. In
this study, Estebany practiced laying–on of hands
healing on various patients. Using her psychic
and intuitive abilities, Kunz would observe and assist
in the healing, while Krieger recorded the activities
of the healing session and created profiles of the
patients.
As the study progressed, Kunz began teaching
Krieger how to heal, based on her perceptions of
Estebany’s healing techniques. During her research
of ancient healing methods, Krieger concluded that
the energy transfer between the healer and the healee
that takes place in a TT session is prana, an Eastern
Indian concept representing energy, vitality, and
vigor. Krieger then combined her research with
Kunz’s techniques to create TT.
TT was initially developed for persons in the
health professions, but is currently taught worldwide to anyone who is interested in learning the
technique. As of 1998, an estimated 100,000 people
around the world have been trained in TT; 43,000
of those persons are health care professionals,
many of whom use TT in conjunction with traditional medicine, as well as osteopathic, chiropractic, naturopathic, and homeopathic therapies. TT
is taught in over 100 colleges, universities, and
medical schools.

Benefits
The major effects of TT are relaxation, pain reduction, accelerated healing, and alleviation of psychosomatic symptoms. Studies have shown that TT has a
beneficial effect on the blood as it has the ability to
raise hemoglobin values. It also affects brain waves to
induce a relaxed state. TT can induce the relaxation
response often within five minutes.
Krieger has said that it is not individual illnesses
that validate the effectiveness of TT, but rather, it is
questioned which systems are most sensitive to TT.
She and others have found that the most sensitive is
the autonomic nervous system (ANS), which, for
example, controls urination. The ANS is followed by
dysfunctions of lymphatic and circulatory systems,
and then finally musculoskeletal systems. In addition,
3672

D O L O R E S K R I E G E R (1935– )
Dolores Krieger, a prominent professor of nursing at
the New York University Division of Nursing, conceived
of therapeutic touch as a healing technique in the early
1970s and introduced the therapy in 1972. Therapeutic
touch rarely consists of physical contact with the patient.
The practitioner focuses positive energy through the
hands, which are held or waved two to three inches
away from the patient, and directs it towards the patient’s
energy field. Krieger developed the technique along with
a colleague, Dora Van Gelder Kunz, who is believed to
be clairvoyant. They initially taught the system to graduate students at the nursing school, and it evolved from
that basis. Since the introduction of therapeutic touch,
Krieger traveled the world in teaching the technique
before she retired as professor emerita at the university.
An estimated 70,000 nurses were trained by Krieger and
Kunz.
In 1981 Dr. Krieger published Foundations for
Holistic Health Nursing Practices. She later published a
manual, The Therapeutic Touch: How to Use Your
Hands to Help or to Heal, in 1992.
Krieger became embroiled in controversy over the
potential benefits of therapeutic touch technique
between 1996-98, when nine-year-old schoolgirl Emily
Rosa challenged the validity of the therapy with a simple
experiment. She gathered 21 practitioners and through a
covered box held her hand over one of the practitioner’s
own to test whether they could sense her energy field.
Only 44% of the time were the practitioners able to
determine which of their hands that Rosa’s was hovering
over. Although Rosa contacted Krieger in 1997, Krieger
refused to meet with her, refused to participate in Rosa’s
experiment, and disputed the relevancy of an elementary
school student’s observations. Krieger holds both an R.N.
and a Ph.D. degree and dismissed the validity of the
experiment due to the student’s and practitioners’ lack
of experience.
Krieger continues to promote her technique; her
latest book, Living the Therapeutic Touch, was published
by in 1999.

the female endocrine system is more sensitive to TT
than the corresponding male system. Thus, TT helps
with dysmenorrhea, amenorrhea, problems with contraception, and the course of pregnancy.
TT is reported to have a positive effect on the
immune system and thus accelerates the healing of
wounds. Nurses use therapeutic touch in operating
rooms to relax patients before surgery and in recovery
rooms on postoperative patients to help speed the
GALE ENCYCLOPEDIA OF MEDICINE

might feel heat, coolness, heaviness, pressure, or a
prickly or tingling sensation. These cues, as they are
called, each signal a blockage or disturbance in the
field.

Many nurses use TT in the nursery. The conditions of many premature babies who received TT
reportedly improved rapidly. TT has been used to
calm colicky infants, assist women in childbirth, and
increase milk let-down in breast-feeding mothers.

To remove these blockages and restore balance to
the body, the practitioner then performs a series of
downward sweeping movements to clear away any
energy congestion and smooth the energy field. This
is known as the unruffling process and is generally
performed from head to feet. To prevent any energy
from clinging to him/her, the practitioner shakes his/
her hands after each stroke.

Other claims of TT include relief of acute pain,
nausea, diarrhea, tension and migraine headaches,
fever, and joint and tissue swelling. TT has been used
to treat thyroid imbalances, ulcers, psychosomatic illnesses, premenstrual syndrome, Alzheimer’s disease,
stroke and coma, multiple sclerosis, measles, infections,
asthma, and bone and muscle injuries.
Therapeutic touch is performed in many different
locations, including healing centers, delivery rooms,
hospitals, hospice settings, accident scenes, homes,
and schools.

Description
Therapeutic touch treats the whole person:
relaxes the mind, heals the body, and soothes the
spirit. The principle behind it is that it does not
stop at the skin. The human body extends an energy
field, or aura, several inches to several feet from the
body. When illness occurs, it creates a disturbance or
blockage in the vital energy field. The TT practitioner uses her/his hands to sense the blockage or
disturbance. In a series of gentle strokes, the healer
removes the disturbance and rebalances the energy to
restore health.
The TT session generally lasts about 20–30 minutes. Although the name is therapeutic touch, there is
generally no touching of the physical body, only the
energetic body or field. It is usually performed on fully
clothed patients who are either lying down on a flat
surface or sitting up in a chair.

During the next phase, the practitioner acts as
a conduit to transfer energy to the patient. The
energy used is not solely the energy of the practitioner. The practitioner relies on a universal source
of energy so as not to deplete his/her own supply.
In short, the healer acts as an energy support
system until the patient’s immune system is able
to take over.
The practitioner then smoothes the field to balance the energy and create a symmetrical flow. When
the session is over, it is recommended that the patient
relax for 10–15 minutes in order for the energies to
stabilize.

Side effects
The side effects reported occur when an excess
of energy enters the body for an extended period
of time creating restlessness, irritability, and hostility, or increasing anxiety and pain. Burns are
sensitive to therapeutic touch, and it is recommended that TT be performed on burned tissue
for short periods, generally two to three minutes
at a time.

Research and general acceptance

Each session consists of five steps. Before the session begins, the practitioner enters a state of quiet
meditation in which he/she becomes centered and
grounded in order to establish intent for the healing
session and to garner the compassion necessary
to heal.

Therapeutic touch is not generally accepted by
Western medical professionals. Basic and anecdotal
research has been performed on TT since its development in 1972, although little quantitative research has
been carried out. It is based on a theory derived from
formal research. It began as the basis of Dolores
Krieger’s postdoctoral research.

The second step involves the assessment of the
person’s vital energy field. During this step, the practitioner places the palms of his/her hands 2–3 in (5–8
cm) from the patient’s body and sweeps them over the
energy field in slow, gentle strokes beginning at the
head and moving toward the feet. The practitioner

Dolores Krieger has performed extensive research
on TT, including with pregnant women, and has noted
that the following changes occur in a patient after
short, consistent treatment: relaxation within the first
five minutes of a session, a reduction of pain, and the
acceleration of the healing process.

GALE ENCYCLOPEDIA OF MEDICINE

3673

Therapeutic touch

healing process. TT is used in the treatment of terminally ill patients, such as those with cancer and autoimmune deficiency syndrome (AIDS), to relieve anxiety
and stress, create peace of mind, and reduce pain.

Thoracentesis

One study was created to determine the effect TT
would have on wounds that resulted from a biopsy of
the upper arm. Forty-four patients placed their
injured arms through a hole in a door. Twenty-two
of them received TT on their arms. The other half
received no treatment. The wounds treated with TT
healed more quickly than the wounds that received
no treatment.
In 1998, a study was performed on 27 patients
with osteoarthritis in at least one knee. For six weeks,
the patients were treated with therapeutic touch, mock
therapeutic touch, or standard care. According to The
Journal of Family Practice, the journal who published
the study, the results showed that the group who had
received TT had ‘‘significantly decreased pain and
improved function as compared with both the placebo
and control groups.’’
Therapeutic touch can be combined with a number of different therapies, including acupressure, massage, mental imagery, physical therapy, and yoga.
When combined with massage and physiotherapy,
TT may reduce tension headaches, back pain, stressrelated problems, circulatory problems, and constipation. Shiatsu and TT may help sinusitis, digestive
disorders, muscle cramps, menstrual difficulties, and
insomnia. Yoga and TT may be beneficial in the treatment of bronchitis, asthma, blood pressure, fatigue,
and anxiety.
TT is practiced in over 70 countries worldwide: by
Egyptians and Israelis during fighting in the Gaza
Strip; in South Africa to reduce racial strife; and in
Poland, Thailand, and the former Soviet Union.

Training and certification
Therapeutic touch is taught at over 100 universities and nursing and medical schools around the
United States and Canada. Although it was developed
primarily for nurses, anyone can learn TT.
State laws vary regarding the practice of TT. In
general, laypersons are allowed to practice TT within
their families. Therapeutic touch is considered an
extension of health care skills, so most health care
professionals are covered under the state medical practice act.
Many hospitals have established policies allowing
nurses and staff to perform TT on patients at no extra
charge. The American Nurse’s Association often
holds workshops on TT at national conventions.
Therapeutic touch classes are often held for the general public through community education, healing
clinics, and holistic schools.
3674

Resources
OTHER

The Nurse Healers Professional Associates International
(NH-PAI), the Official Organization of Therapeutic
Touch. 3760 S. Highland Dr. Salt Lake City, UT 84106.
(801) 273–3399. nhpai@therapeutic-touch.org.
<http://www.therapeutic-touch.org>.

Jennifer Wurges

Thiabendazole see Antihelminthic drugs
Thiamine deficiency see Beriberi

Thoracentesis
Definition
Also known as pleural fluid analysis, thoracentesis is a procedure that removes fluid or air from the
chest through a needle or tube.

Purpose
The lungs are lined on the outside with two thin
layers of tissue called pleura. The space between
these two layers is called the pleural space.
Normally, there is only a small amount of lubricating fluid in this space. Liquid and/or air accumulates
in this space between the lungs and the ribs from
many conditions. The liquid is called a pleural effusion; the air is called a pneumothorax. Most pleural
effusions are complications emanating from metastatic malignancy (movement of cancer cells from
one part of the body to another). Most malignant
pleural effusions are detected and controlled by
thoracentesis. Thoracentesis is also performed as a
diagnostic measure. In these cases, only small
amounts of material need to be withdrawn.
Symptoms of a pleural effusion include breathing
difficulty, chest pain, fever, weight loss, cough, and
edema. Removal of air is often an emergency procedure to prevent suffocation from pressure on the
lungs. Negative air pressure within the chest cavity
allows normal respiration. The accumulation of air
or fluid within the pleural space can eliminate these
normal conditions and disrupt breathing and the
movement of air within the chest cavity. Fluid removal
is performed to reduce the pressure in the pleural space
and to analyze the liquid. In addition, thoracentesis
GALE ENCYCLOPEDIA OF MEDICINE

Thoracentesis often provides immediate abatement
of symptoms. However, fluid often begins to reaccumulate. A majority of patients will ultimately require
additional therapy beyond a simple thoracentesis.
There are two types of liquid in the pleural space,
one having more protein in it than the other. More
watery liquids are called transudates; thicker fluids are
called exudates. On the basis of this difference, the
cause of the effusion can more easily be determined.



Several drugs can damage the lung linings as an
unexpected side effect. None of these drugs is commonly used.



An esophagus perforated by cancer, trauma, or other
conditions can spill liquids and even food into the
chest. The irritation creates an exudate in the pleural
space.



Pancreatic disease can cause massive fluid in the
abdomen, which can then find its way into the chest.



Pericarditis is an inflammation of the sac that contains the heart. It can ooze fluid from both sides–into
the heart’s space and into the chest.



Radiation to treat cancer or from accidents with
radioactive materials can damage the pleura and
lead to exudates.



A wide variety of autoimmune diseases attacks the
pleura. Among these are rheumatoid arthritis and
systemic lupus erythematosus (SLE).



Many other rare conditions can also lead to
exudates.

Transudates
Thin, watery fluid oozes into the chest either
because back pressure from circulation squeezes it
out or because the blood has lost some of its osmotic
pressure.


Heart failure creates back pressure in the veins as
blood must wait to be pumped through the heart.



A pulmonary embolism is a blood clot in the lung. It
will create back pressure in the blood flow and also
damage a part of the lung so that it leaks fluid.



Cirrhosis is a sick, scarred liver that both fails to
make enough protein for the blood and also restricts
the flow of blood through it.



Nephrosis is a collection of kidney disorders that
change the osmotic pressure of blood and allow
liquid to seep into body cavities.



Myxedema is a disease caused by too little thyroid
hormone.
Exudates

Thicker, more viscous fluid is usually due to
greater damage to tissues, allowing blood proteins as
well as water to seep out.


Pneumonia, caused by viruses and by bacteria,
damages lung tissue and can open the way for exudates to enter the pleural space.



Tuberculosis can infect the pleura as well as the lungs
and cause them to leak liquid.



Cancers of many types settle in the lungs or the
pleura and leak liquids from their surface.



Depending upon its size and the amount of damage it
has done, a pulmonary embolism can also produce an
exudate.

GALE ENCYCLOPEDIA OF MEDICINE

Blood
Blood in the chest (hemothorax) is infrequently
seen outside of two conditions:


major trauma can sever blood vessels in the chest,
causing them to bleed into the pleural space



cancers can ooze blood as well as fluid, they do not
usually bleed massively
Chyle

Occasionally, the liquid that comes out of the
chest is neither transparent nor bloody, but milky.
This is due to a tear of the large lymphatic channel–
the thoracic duct carrying lymph fluid from the intestines to the heart. It is milky because it is transporting
fats absorbed in the process of digestion. The major
causes of chylothorax are:


injury from major trauma, such as an automobile
accident



cancers eroding into the thoracic duct
Air

Air in the pleural space is called pneumothorax.
Air can enter the pleural space either directly through
a hole between the ribs or from a hole in the lungs.
Holes in the lungs are sometimes spontaneous, sometimes traumatic, and sometimes the result of disease
opening a communication to the air in the lung.
3675

Thoracentesis

was traditionally used to remove blood from the chest
cavity. This is rare now that the placement of a thoracostomy tube has proven to be a more effective and
safer method.

Thoracic outlet syndrome

Precautions
Care must be taken not to puncture the lung when
inserting the needle. Thoracentesis should never be
performed by inserting the needle through an area
with an infection. An alternative site needs to be
found in these cases. Patients who are on anticoagulant
drugs should be carefully considered for the
procedure.

Description
The usual place to tap the chest is below the
armpit (axilla). Under sterile conditions and local
anesthesia, a needle, a through-the-needle-catheter,
or an over-the-needle catheter may be used to perform
the procedure. Overall, the catheter techniques may be
safer. Fluid or air is withdrawn. Fluid is sent to the
laboratory for analysis. If the air or fluid continue to
accumulate, a tube is left in place and attached to a
one-way system so that it can drain without sucking
air into the chest.

Preparation
The location of the fluid is pinpointed through x
ray or ultrasound. Ultrasound is a more accurate
method when the effusion is small. A sedative may
be administered in some cases but is generally not
recommended. Oxygen should be given to the patient.

Aftercare
As long as the tube is in the chest, the patient must
lie still. After it is removed, x rays will determine if the
effusion or air is reaccumulating%—though some
researchers and clinicians believe chest x rays do not
need to be performed after routine thoracentesis.

KEY TERMS
Axilla—Armpit.
Catheter—A tube that is moved through the body
for removing or injecting fluids into body cavities.
Hypovolemic shock—Shock caused by a lack of
circulating blood.
Osmotic pressure—The pressure in a liquid
exerted by chemicals dissolved in it. It forces a
balancing of water in proportion to the amount of
dissolved chemicals in two compartments separated by a semi-permeable membrane.
Pleura—Two thin layers lining the lungs on the
outside.

structures as the diaphragm, spleen, or liver, can be
damaged by needle insertion. Repeat thoracenteses
can increase the risk of developing hypoproteinemia
(a decrease in the amount of protein in the blood).
Resources
BOOKS

Abeloff, Martin D., et al., editors. Clinical Oncology. New
York: Churchill Livingstone, 2000.
Celli, R. Bartolome. ‘‘Diseases of the Diaphragm, Chest
Wall, Pleura and Mediastinum.’’ In Cecil Textbook of
Medicine, edited by J. Claude Bennett. Philadelphia: W.
B. Saunders, 2000.
PERIODICALS

Colt, Henri G. ‘‘Factors Contributing to Pneumothorax
After Thoracentesis.’’ Chest 117 (February 2000).
Petersen, W.G. ‘‘Limited Utility of Chest Radiograph After
Thoracentesis.’’ Chest 117 (April 2000): 1038-1042.

Mark A. Mitchell, M.D.

Risks
Reaccumulation of fluid or air is a possible complications, as are hypovolemic shock (shock caused by
a lack of circulating blood) and infection. Patients are
at increased risk for poor outcomes if they have a
recent history of anticoagulant use, have very small
effusions, have significant amounts of fluid, have poor
health leading into this condition, have positive airway
pressure, and have adhesions in the pleural space. A
pneumothorax can sometimes be caused by the thoracentesis procedure. The use of ultrasound to guide
the procedure can reduce the risk of pneumothorax.
Thoracentesis can also result in hemothorax, or
bleeding within the thorax. In addition, such internal
3676

Thoracic aortic aneurysm see Aortic
aneurysm
Thoracic empyema see Empyema

Thoracic outlet syndrome
Definition
Thoracic outlet syndromes are a group of disorders that cause pain and abnormal nerve sensations in
the neck, shoulder, arm, and/or hand.
GALE ENCYCLOPEDIA OF MEDICINE

The thoracic outlet is an area at the top of the rib
cage, between the neck and the chest. Several anatomical structures pass through this area, including the
esophagus, trachea, and nerves and blood vessels that
lead to the arm and neck region. The area contains the
first rib; collar bone (clavicle); the arteries beneath the
collar bone (subclavian artery), which supply blood to
the arms; a network of nerves leading to the arms
(brachial plexus); and the top of the lungs.
Pain and other symptoms occur when the nerves
or blood vessels in this area are compressed. The likelihood of blood vessels or nerves in the thoracic outlet
being compressed increases with increased size of body
tissues in this area or with decreased size of the thoracic outlet. The pain of thoracic outlet syndrome is
sometimes confused with the pain of angina that indicates heart problems. The two conditions can be distinguished from each other because the pain of
thoracic outlet syndrome does not appear or increase
when walking, while the pain of angina does. Also, the
pain of thoracic outlet syndrome usually increases if
the affected arm is raised, which does not happen in
cases of angina.
There are three
syndromes:

types

of

thoracic

outlet



True neurogenic thoracic outlet syndrome is caused
by a compression of the nerves in the brachial plexus.
Abnormal muscle or other tissue causes the problem.



Arterial thoracic outlet syndrome is caused by compression of the major artery leading to the arm,
usually by a rib.

can put pressure on blood vessels or nerves. Typical
abnormalities that can cause problems are malformed
ribs and too narrow an opening between the collar bone
and the first rib.
The main symptom is pain in the affected area. The
patient can also develop weakness in the arm and
hands, tingling nerve sensations, and a condition called
Raynaud’s syndrome. In Raynaud’s syndrome, exposure to cold causes small arteries in the fingers to contract, cutting off blood flow. This causes the fingers to
turn pale. In very severe cases of blood vessel compression, gangrene can result. Gangrene is the death of tissue
caused by the blood supply being completely cut off.
In the case of arterial thoracic outlet syndrome,
the artery beneath the collar bone leading to the arm is
compressed, causing the artery to increase in size.
Blood clots (thrombi) may form in the blood vessel.
When blood vessels are compressed, the hands, arms,
and shoulders do not receive proper blood supply.
They can swell and turn blue from a lack of blood.
In the case of true neurogenic thoracic outlet syndrome, the nerves most affected are those of the network of nerves supplying the chest, shoulder, arm,
forearm, and hand (brachial plexus). When a nerve is
affected in thoracic outlet syndrome it produces a
tingling sensation (paresthesia). It can also cause
weakness in the hand and reduced sensation in the
palm and fingers.

Diagnosis

Compression of blood vessels or nerves in the
thoracic outlet causes pain and/or abnormal nerve
sensations. Compression usually occurs at the location
where the blood vessels and nerves pass out of the
thoracic outlet into the arm.

There are no specific diagnostic tests for thoracic
outlet syndromes. The diagnosis is made by ruling out
other diseases and by observing the patient. Two nonspecific tests that can suggest the presence of thoracic
outlet syndrome are the Adson test and the Allen test.
In the Adson test, the patient takes a deep breath and
tilts his or her head back and turns it to one side. The
physician tests to see if the strength of the patient’s
pulse is reduced in the wrist on the arm on the opposite
side of the head turn. In the Allen test, the arm in
which the patient is experiencing symptoms is raised
and rotated while the head is turned to the opposite
side. The physician tests to see if the pulse strength at
the wrist is reduced. If the strength of the pulse is
reduced in either of these two tests it indicates compression of the subclavian artery.

There are several factors that contribute to a person
developing thoracic outlet syndrome. Poor posture is a
major cause and is easy to treat. A person’s physical
makeup also can cause thoracic outlet syndrome. For
example, abnormalities of certain anatomical structures

Occasionally, examination with a stethoscope
may reveal abnormal sounds in affected blood vessels.
X rays can reveal constrictions in blood vessels if a
special dye is injected into the blood stream to make
the blood vessels visible (angiography).



Disputed thoracic outlet syndrome describes patients
who have chronic pain in the shoulders and arms and
have no other disease or syndrome, but the underlying cause cannot be accurately determined.

Thoracic outlet syndrome is most common in
women who are 35 to 55 years of age.

Causes and symptoms

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Thoracic outlet syndrome

Description

Thoracic surgery

Resources

KEY TERMS

BOOKS

Angina—A severe constricting pain in the
chest, usually caused by a lack of oxygen to
the heart.
Neurogenic—Caused by nerves; originating in the
nerves.
Subclavian—Located
(clavicle).

beneath

the

Berkow, Robert, editor. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 1997.

John T. Lohr, PhD

collarbone

Thoracic surgery
Certain tests are available to help with the
diagnosis of nerve compression. These include the
nerve conduction velocity test and somatosensory
evoked potential test. In the nerve conduction velocity test, electrodes are placed at various locations
on the skin along a nerve that is being tested. A
mild electrical impulse is delivered through an electrode at one end of the nerve and the electrical
activity is recorded by the other electrodes. The
time it takes for the electrical impulse to travel
down the nerve from the stimulating electrodes to
the recording electrodes is used to calculate the
nerve conduction velocity. This can be used to
determine if any nerve damage exists.
In a somatosensory evoked potential test, electrodes are placed on the skin at the scalp, neck,
shoulder, and wrist. A mild electrical impulse is delivered at the wrist, and a recording is made of the
response by the brain and spinal cord. This test also
can determine the presence of nerve damage.

Treatment
The main treatment for thoracic outlet syndrome is physical therapy. Exercises aimed at
improving the posture of the affected person are
also useful. In some cases, surgery can be performed
to remove the cervical rib if this is causing the problem and physical therapy has failed to work.
However, surgery is generally not used to treat thoracic outlet syndrome.

Prognosis
Treatment of true neurogenic and arterial thoracic outlet syndromes is usually successful. Treatment
of disputed thoracic outlet syndrome is often unsuccessful. This may relate to the uncertainty of the
underlying cause of the pain.
3678

Definition
Thoracic surgery is the repair of organs located in
the thorax, or chest. The thoracic cavity lies between
the neck and the diaphragm, and contains the heart
and lungs (cardiopulmonary system), the esophagus,
trachea, pleura, mediastinum, chest wall, and
diaphragm.

Purpose
Thoracic surgery repairs diseased or injured
organs and tissues in the thoracic cavity. General
thoracic surgery deals specifically with disorders of
the lungs and esophagus. Cardiothoracic surgery also
encompasses disorders of the heart and pericardium.
Blunt chest trauma, reflux esophagitis, esophageal
cancer, lung transplantation, lung cancer, and emphysema are just a few of the many clinical indications for
thoracic surgery.

Precautions
Patients who have blood-clotting problems
(coagulopathies), and who have had previous standard thoracic surgery may not be good candidates for video-assisted thoracic surgery (VATS).
Because VATS requires the collapse of one lung,
potential patients should have adequate respiratory function to maintain oxygenation during the
procedure.

Description
Thoracic surgery is usually performed by a surgeon who specializes in either general thoracic surgery
or cardiothoracic surgery. The patient is placed under
general anesthesia and endotracheally intubated for
the procedure. The procedure followed varies according to the purpose of the surgery. An incision that
opens the chest (thoracotomy) is frequently performed
GALE ENCYCLOPEDIA OF MEDICINE

Candidates for thoracic surgery should be fully
educated by their physician or surgeon on what
their surgery will involve, the possible risks and
complications, and requirements for postoperative
care.
Patients are instructed not to eat 10 to 12 hours
prior to a thoracic surgery procedure. A sedative
may be provided to relax the patient prior to surgery. An intravenous line (IV) is inserted into the
patient’s arm or neck to administer fluids and/or
medication.

Video-assisted thoracic surgery (VATS) is a
minimally invasive surgical technique that uses a
thoracic endoscope (thoracoscope) to allow the surgeon to view the chest cavity. A lung is collapsed and
3-4 small incisions, or access ports, are made to facilitate insertion of the thoracoscope and the surgical
instruments. During the procedure, the surgeon
views the inside of the pleural space on a video monitor. The thoracoscope may be extracted and inserted
through a different incision site as needed. When the
surgical procedure is complete, the surgeon expands
the lung and inserts a chest tube in one of the incision
sites. The remaining incisions are sealed with
adhesive.

After surgery, the patient is taken to the recovery
room, where vital signs are monitored; depending on
the procedure performed, the breathing tube may be
removed. The patient typically experiences moderate
to severe pain following surgery. Analgesics or other
pain medication are administered to keep the patient
comfortable. Chest tubes are monitored closely for
signs of fluid or air accumulation in the lungs that
can lead to lung collapse. A urinary catheter will
remain in the patient for 24 to 48 hours to drain
urine from the bladder.

The thoracic surgeon may also use a mediastinoscope or a bronchoscope to explore the thoracic
cavity. Mediastinoscopy allows visualization of the
mediastinum, the cavity located between the lungs.
The bronchoscope enables the surgeon to view the
larynx, trachea, and bronchi. These instruments
may be used in a separate diagnostic procedure
prior to thoracic surgery, or during the surgery
itself.

The hospital stay for thoracic surgery depends
on the specific procedure performed. Patients who
undergo a thoracotomy may be hospitalized a week
or longer, while patients undergoing VATS typically have a shorter hospital stay of 2-3 days.
During the recovery period, respiratory therapists
and nurses work with the patient on deep breathing and coughing exercises to improve lung
function.

Preparation
Except in the case of emergency procedures,
candidates for general thoracic surgery should
undergo a complete medical history and thorough
physical examination prior to surgery. Particular
attention is given to the respiratory system. The
patient’s smoking history will be questioned. If
the patient is an active smoker, encouragement is
always given for the patient to quit smoking prior
to the surgery to facilitate recovery and reduce
chances of complications.
Diagnostic tests used to evaluate the patient preoperatively may include, but are not limited to,
x rays, MRI, CT scans, blood gas analysis, pulmonary
function tests, electrocardiography, endoscopy, pulmonary angiography, and sputum culture.
GALE ENCYCLOPEDIA OF MEDICINE

Aftercare

Risks
Respiratory failure, hemorrhage, nerve injury,
heart attack, stroke, embolism, and infection are all
possible complications of general thoracic surgery.
The chest tubes used for drainage after thoracic surgery may cause a build-up of fluid or the accumulation
of air in the pleural space. Both of these conditions
can lead to total lung collapse. Other specific complications may occur, depending on the procedure
performed.

Normal results
Normal results of thoracic surgery are dependent
on the type of procedure performed and the clinical
purpose of the surgery.
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Thoracic surgery

to give the surgeon access to the thoracic cavity.
Commonly, the incision is made beginning on the
back under the shoulder blade and extends in a curved
arc under the arm to the front of the chest. The muscles
are cut, and the ribs are spread with a retractor. The
surgeon may also choose to open the chest through an
incision down the breastbone, or sternum (sternotomy). Once the repair, replacement, or removal of
the organ being operated on is complete, a chest tube
is inserted between the ribs to drain the wound and reexpand the lung.

Thoracoscopy

KEY TERMS
Blood gas analysis—A blood test that measures the
level of oxygen, carbon dioxide, and pH in arterial
blood. A blood gas analysis can help a physician
assess how well the lungs are functioning.
Electrocardiography—A cardiac test that measures
the electrical activity of the heart.
Embolism—A blood clot, air bubble, or clot of foreign
material that blocks the flow of blood in an artery.
When blood supply to a tissue or organ is blocked by
an embolism, infarction, or death of the tissue that
the artery feeds, occurs. Without immediate and
appropriate treatment, an embolism can be fatal.
Emphysema—A lung disease characterized by
shortness of breath and a chronic cough.
Emphysema is caused by the progressive stretching
and rupture of alveoli, the air sacs in the lung that
oxygenate the blood.

Thoracoscopy
Definition
Thoracoscopy is the insertion of an endoscope, a
narrow–diameter tube with a viewing mirror or camera attachment, through a very small incision (cut) in
the chest wall.

Purpose
Thoracoscopy makes it possible for a physician
to examine the lungs or other structures in the chest
cavity, without making a large incision. It is an alternative to thoracotomy (opening the chest cavity with
a large incision). Many surgical procedures, especially taking tissue samples (biopsies), can also be
accomplished with thoracoscopy. The procedure is
done to:


assess lung cancer



take a biopsy for study



determine the cause of fluid in the chest cavity

Intubation—Insertion of an endotracheal tube
down the throat to facilitate airflow to the lung(s)
during thoracic surgery.
Pericardium—The sac around the heart.



introduce medications or other treatments directly
into the lungs



treat accumulated fluid, pus (empyema), or blood in
the space around the lungs

Pleural space—The space between the pleural
membranes that surround the lungs and the chest
cavity.
Pulmonary angiography—An x-ray study of the
lungs, performed by insertion of a catheter into a
vein, through the heart, and into the pulmonary
artery. Pulmonary angiography is performed to
evaluate blood circulation to the lungs. It is also
considered the most accurate diagnostic test for
detecting a pulmonary embolism.
Sputum culture—A laboratory analysis of the fluid
produced from the lungs during coughing. A sputum culture can confirm the presence of pathogens
in the respiratory system, and help to diagnose
certain respiratory infections, including bronchitis,
tuberculosis, and pneumonia.

For many patients, thoracoscopy replaces thoracotomy. It avoids many of the complications of open
chest surgery and reduces pain, hospital stay, and
recovery time.

Endoscopy—The examination of organs and body
cavities using a long, tubular optical instrument
called an endoscope.

Resources

Precautions
Because one lung is partially deflated during
thoracoscopy, the procedure cannot be done on
patients whose lung function is so poor that they do
not receive enough oxygen with only one lung.
Patients who have had previous surgery that involved
the chest cavity, or who have blood clotting problems, are not good candidates for this procedure.
Thoracoscopy gives physicians a good but limited
view of the organs, such as lungs, in the chest cavity.
Endoscope technology is being refined every day, as is
what physicians can accomplish by inserting scopes
and instruments through several small incisions
instead of making one large cut.

ORGANIZATIONS

American Thoracic Society. 1740 Broadway, New York, NY
10019. (212) 315-8700. <http://www.thoracic.org>.

Paula Anne Ford-Martin
3680

Description
Thoracoscopy is most commonly performed in a
hospital, and general anesthesia is used. Some of the
GALE ENCYCLOPEDIA OF MEDICINE

Thoracoscopy
Thoracoscopy is a procedure in which a physician can view the chest cavity and the lungs by inserting an endoscope
through the chest wall. Thoracoscopy is less evasive than surgical lung biopsy. (Illustration by Electronic Illustrators
Group.)

procedures are moving toward outpatient services and
local anesthesia. More specific names are sometimes
applied to the procedure, depending on what the target site of the effort is. For example, if a physician
intends to examine the lungs, the procedure is often
called pleuroscopy. The procedure takes two to four
hours.
The surgeon makes two or three small incisions
in the chest wall, often between the ribs. By making the incisions between the ribs, the surgeon
minimizes damage to muscle and nerves and the
ribs themselves. A tube is inserted in the trachea
and connected to a ventilator, which is a mechanical device that assists the patient with inhaling and
exhaling.
The most common reason for a thoracoscopy is to
examine a lung that has a tumor or a metastatic
growth of cancer. The lung to be examined is deflated
to create a space between the chest wall and the lung.
The patient breathes with the other lung with the
assistance of the ventilator.
A specialized endoscope, or narrow–diameter
tube, with a video camera or mirrored attachment, is
inserted through the chest wall. Instruments for taking
necessary tissue samples are inserted through other
small incisions. After tissue samples are taken, the
lung is reinflated. All incisions except one are closed.
The remaining open incision is used to insert a drainage tube. The tissue samples are sent to a laboratory
for evaluation.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Endoscope—Instrument designed to allow direct
visual inspection of body cavities, a sort of microscope in a long access tube.
Thoracotomy—Open chest surgery.
Trachea—Tube of cartilage that carries air into and
out of the lungs.

Preparation
Prior to thoracoscopy, the patient will have several
routine tests, such as blood, urine and chest x ray. Older
patients must have an electrocardiogram (a trace record
of the heart activity) because the anesthesia and the
lung deflation put a big load on the heart muscle. The
patient should not eat or drink from midnight the night
before the thoracoscopy. The anesthesia used can cause
vomiting, and, because anesthesia also causes the loss of
the gag reflex, a person who vomits is in danger of
moving food into the lungs, which can cause serious
complications and death.

Aftercare
After the procedure, a chest tube will remain in
one of the incisions for several days to drain fluid and
release residual air from the chest cavity. Hospital
3681

Threadworm infection

stays range from two to five days. Medications for
pain are given as needed. After returning home,
patients should do only light lifting for several weeks.

Risks
The main risks of thoracoscopy are those associated with the administration of general anesthesia.
Sometimes excessive bleeding, or hemorrhage,
occurs, necessitating a thoracotomy to stop it.
Another risk comes when the drainage tube is
removed, and the patient is vulnerable to lung collapse (pneumothorax).

as 25% of the population in some developing countries. In the United States, threadworm infection is
most likely to be found among immigrants; returning
travelers or military personnel; people who live in
parts of Appalachia and the southeastern states;
and persons in homes for the retarded and similar
institutions.
Human beings are universally susceptible to
threadworm infection, although adults and older children are at greater risk of infection than younger
children. The disease does not confer immunity. In
addition to humans, threadworms can infect dogs,
cats, horses, pigs, rats, and monkeys.

Resources

Causes and symptoms

PERIODICALS

Dardes, N., E.P. Graziani, I. Fleishman, and M. Papale.
‘‘Medical Thoracoscopy in Management of Pleural
Effusions.’’ Chest 118, no. 4 (October 2000): 129s.
Shawgo, T., T.M. Boley, and S. Hazelrigg.‘‘The Utility of
Thoracoscopic Lung Biopsy for Diagnosis and
Treatment.’’ Chest 118, no. 4 (October 2000): 114s.

Tish Davidson, A.M.

Thoracotomy see Lung surgery; Thoracic
surgery
Threadworm see Enterobiasis

Threadworm infection
Definition
Threadworm infection is an intestinal disease,
which occasionally spreads to the skin, caused by a
type of parasitic roundworm (helminth). In untreated
patients, the disease has a high rate of reinfection
caused by worms already present in the body. This
type of disease recurrence is called autoinfection.
Because of autoinfection, threadworms can remain
inside humans for as long as 45 years after the initial
infestation.

Description
Threadworm infection, which is also called
strongyloidiasis, occurs in most countries of the
world but is natural to (endemic in) tropical and
subtropical climates. Strongyloidiasis is less common
than other parasitic infections but may affect as much
3682

Threadworm
infection
is
caused
by
Strongyloides stercoralis, a roundworm that lives in
soil and can survive there for several generations.
Mature threadworms may grow as long as 1–2 in
(2.5–5 cm). The larvae have two stages in their life
cycle: a rod-shaped (rhabdoid) first stage, which is
not infective; and a threadlike (filariform) stage, in
which the larvae can penetrate intact human skin and
internal tissues.
The infection is most commonly transmitted
when a person comes into contact–usually by walking barefoot–with soil containing S. stercoralis larvae in their filariform stage. The threadlike larvae
penetrate the skin, enter the lymphatic system, and
are carried by the blood to the lungs. Once in the
lungs, the larvae burst out of the capillaries into the
patient’s main respiratory system. They migrate
upwards–usually without symptoms–to the patient’s
throat, where they are swallowed and carried down
into the digestive tract. The filariform larvae settle in
the small intestine. They mature into adults that
deposit eggs that hatch–usually in the intestines–
into noninfectious rhabdoid larvae. The rhabdoid
larvae then migrate into the patient’s large intestine
and are excreted in the feces. The time from initial
penetration of the skin to excretion is 17–28 days. The
rhabdoid larvae metamorphose into the infective
filariform stage in the soil.
Threadworms are unique among human parasites
in having both free-living and parasitic forms. In the
free-living life cycle, some rhabdoid larvae develop
into adult worms that live in contaminated soil and
produce eggs that hatch into new rhabdoid larvae. The
adult worms may live as long as five years.
The signs and symptoms of threadworm infection
vary according to the stage of the disease as the larvae
GALE ENCYCLOPEDIA OF MEDICINE

Skin
The filariform larvae usually enter the body
through the skin of the feet. There may be swelling,
itching, and hives at the point of entry that may be
confused with insect bites. Patients with chronic
threadworm infection may also develop an itchy rash
on their buttocks, thighs, or abdomen.
Digestive tract
Although some patients may notice only mild
diarrhea and cramps, others may have fever, nausea,
vomiting, general weakness, and blood or mucus in
their stools. The pain may mimic a stomach ulcer.
Throat and lungs
When the larvae migrate to the lungs and air
passages, the patient may have symptoms ranging
from a simple dry cough to fever, difficulty breathing,
and coughing up blood or pus.
Hyperinfection syndrome
Hyperinfection syndrome is a potentially fatal set
of complications resulting from the spread of filariform larvae to the lungs and other organ systems. It
can include inflammation of the heart tissue, stomach
ulcers, perforation of the intestines, blood poisoning,
meningitis, shock, and eventual death. Hyperinfection
syndrome is most likely to occur in patients with
immune disorders or malnutrition, or in those taking
anti-inflammatory corticosteroid (anti-inflammatory)
medications. It has been reported in only a few AIDS
patients.
Autoinfection
Threadworm autoinfection in humans follows
two patterns. In internal autoinfection, some rhabdoid
larvae in the lower bowel develop into filariform larvae that enter the bloodstream from the intestines and
migrate to the lungs. In external autoinfection, the
skin around the patient’s anus is infected by larvae in
the feces.

military service in areas where the disease is endemic.
A definite diagnosis is made by finding rhabdoid or
filariform larvae in the patient’s body fluids. The larvae may be found in fresh stool specimens or in mucus
coughed up when the infection has reached the lungs.
Because the larvae cannot be detected in the stools of
25% of infected patients, the string test is often performed to confirm the diagnosis. In this test, the
patient swallows a weighted string which is withdrawn
after four hours. The digestive juices absorbed by the
string are then examined for the presence of threadworm larvae.
Doctors can also use blood tests and diagnostic
imaging to support the diagnosis. Between 85% and
95% of patients with threadworm infections will have
a measurable level of antibodies in their blood, even
though these antibodies do not prevent the disease
from spreading. In addition, patients with severe infections often have unusually high levels of white cells in
their blood. X rays of the intestines or the chest often
help in locating specific areas of inflamed or ulcerated
tissue.

Treatment
Threadworm infections are treated with medications. The drugs most often given are ivermectin, thiabendazole (Mintezol), and albendazole. Ivermectin
is generally preferred because it has fewer side effects
than thiabendazole. These drugs, which are taken
by mouth over a period of two to seven days, work
by preventing the development of eggs and new
larvae. Patients with severe infections should be
given protein replacement, blood transfusions, and
fluids to replace losses from nausea, vomiting, and
diarrhea.
Patients who are taking corticosteroids should be
carefully evaluated if they have symptoms of threadworm infection, because these medications encourage
the development of hyperinfection syndrome.

Prognosis
The prognosis for complete recovery is good for
most patients, except those with hyperinfection syndrome or severe protein loss.

Prevention
Diagnosis
The doctor is likely to consider a diagnosis of
threadworm infection when a patient has the symptoms described earlier and a history of travel or
GALE ENCYCLOPEDIA OF MEDICINE

There is no effective immunization against
threadworm infection. Prevention of the disease
requires careful attention to personal and institutional hygiene in endemic areas, including
3683

Threadworm infection

migrate throughout the body. Patients who suffer
from autoinfection may have chronic or intermittent
symptoms for years after they are first infected.

Throat culture

KEY TERMS
Antibody—A protein molecule produced by the
immune system that is specific to a disease agent,
such as threadworm larvae. The severity of a
patient’s infection can be measured from the level
of antibody in the blood.
Autoinfection—An infection caused by a disease
agent that is already present in the body.
Corticosteroid—A class of drugs based on hormones formed in the adrenal gland, used to reduce
inflammation. They increase the likelihood of
hyperinfection syndrome in patients with threadworm infection.
Endemic—Natural to or characteristic of a particular
place, population, or climate. Threadworm infections are endemic in the tropics.
Filariform—Threadlike in appearance, like the
infectious stage of the threadworm larva.
Helminth—A type of parasitic worm. Threadworms
belong to a subcategory of helminths called nematodes, or roundworms.
Hyperinfection syndrome—A condition of massive
infection in which threadworm larvae multiply
rapidly and spread throughout the body. It is usually
associated with damage to the immune system, the
use of steroid medications, or malnutrition.
Rhabdoid—Rod- or wand-shaped, like the first
stage of the threadworm larva.
String test—A test performed to diagnose threadworm infection. The patient is asked to swallow a
weighted string that absorbs stomach juices, which
can be analyzed for the presence of threadworm
larvae.

handwashing after defecating and before handling
food. Other precautions include wearing shoes when
visiting countries with high rates of threadworm
infection, and monitoring close contacts of patients
for signs of infection.

Definition
A throat culture is a technique for identifying
disease bacteria in material taken from the throat.
Most throat cultures are done to rule out infections
caused by beta-hemolytic streptococci, which cause
strep throat. Hemolytic means that these streptococci
destroy red blood cells.

Purpose
The primary purpose of a throat culture is identification of the specific organisms that cause strep
throat. These organisms are Group A streptococci,
specifically Streptococcus pyogenes. Since most sore
throats are caused by viral infections rather than by
S. pyogenes, a correct diagnosis is important to prevent unnecessary use of antibiotics and to begin treatment of strep infections as soon as possible. Group A
streptococcal infections are potentially life-threatening, often involving other parts of the body in addition
to the throat. Besides causing sore throat (pharyngitis),
streptococci can also cause scarlet fever, rheumatic
fever, kidney disease, or abscesses around the tonsils.
Throat cultures can also be used to identify other
disease organisms that are present in the patient’s
throat; and to identify people who are carriers of the
organisms that cause meningitis and whooping cough.
Besides their use in diagnosis, throat cultures are
sometimes used to test antibiotics for their effectiveness in treating different infections.

Precautions
Throat cultures should be taken before the patient
is given any antibiotic medications. In addition, the
patient’s immunization history should be checked to
evaluate the possibility that diseases other than strep
are causing the sore throat. The care provider should
wash the hands carefully after taking the specimen to
prevent the spread of any infectious organisms.

Description

Resources
BOOKS

Goldsmith, Robert S. ‘‘Infectious Diseases: Protozoal &
Helminthic.’’ In Current Medical Diagnosis and
Treatment, 1998, edited by Stephen McPhee, et al., 37th
ed. Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD
3684

Throat culture

A throat culture test should be done on anyone
who has symptoms of a strep throat. These symptoms
include a sore throat that may be accompanied by a
fever, body aches, and loss of appetite. Age is a consideration, in that strep throat is more common in
children than in adults. The tonsils and the back of
the throat often appear red, swollen, and streaked with
GALE ENCYCLOPEDIA OF MEDICINE

Alternative procedures

This nurse is taking a throat culture from a patient for laboratory analysis. (Photograph by David Weinstein & Associates,
Custom Medical Stock Photo. Reproduced by permission.)

So-called instant strep tests are now available
to help diagnose strep throat. They can be used in
the doctor’s office and take about 10–30 minutes
to perform. Instant tests detect an antigen associated with the streptococcus. These tests are relatively new and not available at all clinics. Their
reliability has improved since they were first introduced. If an instant throat test is negative, however, a standard throat culture can be performed to
verify the results.

Preparation
pus. These symptoms usually appear one to three days
after being exposed to group A strep. Because strep is
highly contagious, family members and close contacts
of patients diagnosed with strep throat should also
have throat cultures performed if they show signs of
the disease.
The specimen for throat culture is obtained by
wiping the patient’s throat with a cotton swab. The
patient is asked to tilt the head back and open the
mouth wide. With the tongue depressed and the
patient saying ‘‘ah,’’ the care provider wipes the back
of the throat and the tonsils with a sterile swab. The
swab is applied to any area that appears either very red
or discharging pus. The swab is removed gently without touching the teeth, gums, or tongue. It is then
placed in a sterile tube for immediate delivery to a
laboratory. Obtaining the specimen takes less than
30 seconds. Laboratory results are usually available
in two to three days. The swabbing procedure may
cause gagging but is not painful. The doctor makes a
note for the laboratory to indicate if any disease
organisms other than strep are suspected, because
some require special growth conditions in the
laboratory.
S. pyogenes is cultured on a growth medium
called blood agar. Agar is a gel that is made from
the cell walls of red algae. Blood agar is made from
GALE ENCYCLOPEDIA OF MEDICINE

The patient does not need to avoid food or fluids
before the test. Recent gargling or treatment with
antibiotics, however, will affect the culture results.
The laboratory should be notified if the patient has
been recently taking antibiotic medications.

Aftercare
No specific aftercare is needed.

Risks
There is a minor risk for the health professional of
exposure to the patient’s illness.

Normal results
Normal results would include finding organisms
that grow in healthy throat tissues. These organisms
include non-hemolytic and alpha-hemolytic streptococci, some Neisseria species, staphylococci, diphtheria
and hemophilus organisms, pneumococci, yeasts, and
Gram-negative rods.

Abnormal results
In addition to S. pyogenes, other disease agents
may be identified in the throat culture. Infectious
agents that can be identified include Candida albicans, which can cause thrush; Corynebacterium
3685

Throat culture

agar gel and sheep’s blood. When the throat swab
reaches the laboratory, it is wiped across a blood agar
plate. The plate is allowed to incubate for 24–48
hours to allow the growth of bacteria. If the organism
is a Group A hemolytic streptococcus, the area immediately around the bacterial colony will be cleared of
red blood cells. Hemolytic streptococci dissolve (lyse)
red blood cells, leaving a clear zone surrounding the
colony.

Thrombocytopenia

KEY TERMS
Agar—A gel made from red algae that is used to
culture certain disease agents in the laboratory.
Antibiotic—A drug given to stop the growth
of bacteria. Antibiotics are ineffective against
viruses.
Antigen—A substance that interacts with an antibody and causes an immune reaction.
Carrier—A person harboring an infectious disease
who may be immune to it but who can give it to
others.
Diphtheria—A serious disease caused by a bacterium, Corynebacterium diphtheriae.
Hemolytic—Able to dissolve red blood cells. The
bacteria that cause strep throat are hemolytic
organisms.
Streptococcus—A category (genus) of sphere-shaped
bacteria that occur in pairs or chains.
Thrush—A disease occurring in the mouth or
throat that is caused by a yeast, Candida
albicans.
Whooping cough—An infectious disease of the
respiratory tract caused by a bacterium, Bordetella
pertussis.

diphtheriae, which can cause diphtheria; and
Bordetella pertussis, which can cause whooping
cough. In addition, the appearance of a normal
organism in very high numbers may also be regarded
as an abnormal result.
Resources
ORGANIZATIONS

American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://www
.ama-assn.org>.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Cindy L. A. Jones, PhD

Thromboangiitis obliterans see Buerger’s
disease
Thrombocyte count see Platelet count
3686

Thrombocytopenia
Definition
Thrombocytopenia is an abnormal drop in the
number of blood cells involved in forming blood
clots. These cells are called platelets.

Description
Thrombocytopenia is a blood disease characterized by an abnormally low number of platelets in the
bloodstream. The normal amount of platelets is
usually between 150,000 and 450,000 cells per microliter of blood. A microliter is an amount equal to one
one-millionth of a liter (a liter is almost equal to a
quart). Platelet numbers are counted by having a
blood sample collected and placing a measured
amount of blood in a machine called a cell counter.
When the platelet number drops below 150,000 cells
per microliter of blood, this person is said to be
thrombocytopenic.

Causes and symptoms
Abnormal reductions in the number of platelets
are caused when abnormalities occur in any of the
following three processes: decreased platelet production by the bone marrow; increased trapping of platelets by the spleen; or a more rapid than normal
destruction of platelets. Persons with this condition
easily bruise and can have episodes of excess bleeding
(a hemorrhage).
Platelets come from megakaryocytes, which are
produced in the material located within the center
cavity of the bones (bone marrow). When abnormalities develop in the marrow, the marrow cells can lose
their ability to produce platelets in correct amounts.
The result is a lower than normal level of platelets in
the blood. Drugs used in cancer chemotherapy can
cause the marrow to malfunction in this way, as can
the presence of tumor cells in the marrow itself.
Normally, the spleen holds about one-third of the
body’s platelets as part of this organ’s function to
recycle aging or damaged red blood cells (the cells
that carry oxygen in the blood). When liver disease or
cancer of the spleen is present, the spleen can enlarge,
resulting in a greater number of platelets staying in the
organ. This condition results in abnormally low numbers of platelets in the blood.
Platelets can break down in unusually high
amounts in persons with abnormalities in their blood
vessel walls; with blood clots; or with man-made
GALE ENCYCLOPEDIA OF MEDICINE

Gamma globulin—One of a group of proteins
found in the blood that is involved in helping the
body fight infections.
Stent—A man-made surgical device, usually tubeshaped, that is placed into a blood vessel to keep it
from closing.
Transfusion—The transfer of blood from one person to another. Transfusions can be direct, in which
blood is transferred from the donor to the recipient;
or indirect, in which the blood is taken from the
donor, stored in a container, and then given to the
recipient.

If low platelet levels are due to an abnormally low
level of platelet production, transfusions of platelets
can be given as well.

Prognosis
Thrombocytopenia can result in fatal bleeding,
but it also can indicate various other, more serious,
cancers and disorders that affect the blood cells. This
condition requires thorough medical evaluation.

Prevention
There is no known way to prevent hrombocytopenia.
Resources
ORGANIZATIONS

replacement heart valves. Devices placed inside blood
vessels to keep them from closing (stents) due to weakened walls or fat build-up can also cause platelets to
break down. In addition, infections and other changes
in the immune system can speed up the removal of
platelets from the circulation.

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dominic De Bellis, PhD

Diagnosis
Thrombocytopenia is diagnosed by having a
blood sample taken and counting the platelets present
in the sample. However, accurately determining the
medical reason for this conditions is complex.
Once a low platelet count is verified, a careful
evaluation of the function of the bone marrow and
spleen are necessary. Improper functioning of either or
both of these organs can cause thrombocytopenia. In
addition, the causes for the abnormal spleen or marrow function must be investigated since different cancers, blood disorders, or liver disease can be the true
cause for the drop in platelets found in the blood.

Treatment
If low platelet counts are caused by an enlarged
spleen, removal of the spleen can help raise the platelet
level, since the spleen is no longer there to capture the
platelets. However, proper treatment for what causes
the enlarged spleen is necessary as well.
Low platelet counts can indicate more serious
conditions. If a dysfunctional immune system is
found to be the cause for this condition, drugs like
steroids or gamma globulin can be used to help maintain platelet levels in certain cases.
GALE ENCYCLOPEDIA OF MEDICINE

Thrombocytosis
Definition
Thrombocytosis is a blood disorder in which the
body produces a surplus of platelets (thrombocytes).

Description
Thrombocytosis is an abnormally increased number of platelets in the blood. Platelets are blood cells
that stick together, helping blood to clot.
Thrombocytosis is a condition that may have many
causes.
Throbocytosis is classified as one of two types.
Secondary thrombocytosis can be traced to another
cause, such as inflammation, severe bleeding, iron
deficiency, or some cancers. Primary thrombocytosis
(or essential thrombocythemia) is a single disease
entity, with unique clinical characteristics.

Causes and symptoms
The cause of essential thrombocytosis is unknown.
Secondary thrombocytosis may develop as a
result of:
3687

Thrombocytosis

KEY TERMS

Thrombocytosis

A doctor should be notified whenever bleeding is
unexplained or prolonged or the patient develops:



acute hemorrhage or infection



anemia



arthritis and other chronic inflammations



chest or leg pain



cancer



confusion



exercise



numbness



iron deficiency



weakness



medication



csteoporosis



removal of the spleen (splenectomy)



polycythemia vera (a disorder affecting other red
blood cells, as well as platelets)



stress



surgery

Diagnosis
The patient’s symptoms suggest the presence of
thrombocytosis. Blood tests confirm the diagnosis.
Bone marrow aspiration (removal of a tissue
sample for microscopic examination) may also be
performed.

Treatment

Symptoms
Two of every three patients who have thrombocytosis do not have any symptoms of the disease at the
time of diagnosis. Younger patients may remain symptom-free for years.

The key to treating secondary thrombocytosis is
treating the underlying condition.

Enlargement of the spleen is detected in 60% of
patients with thrombocytosis. The liver may also be
enlarged. As many as half of all patients experience
bleeding from the skin, gums, or nose; and 20–50%
have some blockage of veins or arteries.

In young people who have no symptoms, this
condition can remain stable for many years. These
patients should be monitored by a physician, but
may not require treatment.

Other symptoms of thrombocytosis include:

Any patient who has thrombocytosis should be
encouraged not to smoke.

Treatment for patients who do have symptoms
focuses on controlling bleeding, preventing the formation of blood clots, and lowering platelet levels.
Treatment for secondary thrombocytosis involves
treating the condition or disease responsible for excess
platelet production.



bloody stools



bruising



dizziness



headache



hemorrhage



prolonged bleeding after having surgery or after having a tooth pulled



redness or tingling of the hands and feet

In 1997, the United States Food and Drug
Administration (FDA) approved the use of anagrelide
HCl (Agrylin) to reduce elevated platelet counts and
decrease the risk of clot formation. Some patients have
benefited from the use of hydroxyurea, an anti-cancer
drug.



weakness. In rare instances, the lymph nodes become
enlarged

Low doses of aspirin may prevent clotting, but can
cause serious hemorrhages.

The highest platelet counts usually produce the
most severe symptoms. Younger patients (especially
women) may not have symptoms, even though their
platelet counts are very high.

If drug therapy does not bring platelet counts
down to an acceptable level as rapidly as necessary,
plateletpheresis may be performed. Usually combined
with drug therapy and used primarily in medical emergencies, this procedure consists of:

Complications
Complications of thrombocytosis include stroke,
heart attack, and formation of blood clots in the arms
and legs.
3688



withdrawing blood from the patient’s body



removing platelets from the blood



returning the platelet-depleted blood to the patient
GALE ENCYCLOPEDIA OF MEDICINE

Many patients with thrombocytosis remain free of
complications for long periods. However, some
patients may die as a result of blood clots or uncontrolled bleeding.

(Eminase), streptokinase (Streptase, Kabikinase),
urokinase (Abbokinase), and tissue plasminogen activator (TPA) to dissolve clots. These drugs are given as
injections, only under a physician’s supervision.

Recommended dosage
Prevention
There is no known way to prevent thrombocytosis.
Resources
OTHER

The physician supervising thrombolytic therapy
decides on the proper dose for each patient. He or
she will take into account the type of drug, the purpose
for which it is being used, and in some cases, the
patient’s weight.

‘‘Primary Thrombocythemia.’’ The Merck Page. June 3,
1998. <http://www.merck.com>.

Maureen Haggerty

Thromboembolism see Embolism

Thrombolytic therapy
Definition
Thrombolytic therapy is the use of drugs that
dissolve blood clots.

Purpose
When a blood clot forms in a blood vessel, it may
cut off or severely reduce blood flow to parts of the
body that are served by that blood vessel. This can
cause serious damage to those parts of the body. If the
clot forms in an artery that supplies blood to the heart,
for example, it can cause a heart attack. A clot that
cuts off blood to the brain can cause a stroke.
Thrombolytic therapy is used to dissolve blood clots
that could cause serious, and possibly life-threatening,
damage if they are not removed. Research suggests
that when used to treat stroke, thrombolytic therapy
can prevent or reverse paralysis and other problems
that otherwise might result.
Thrombolytic therapy also is used to dissolve blood
clots that form in tubes put into people’s bodies for
medical treatments, such as dialysis or chemotherapy.

Description
Thrombolytic therapy uses drugs called thrombolytic agents, such as alteplase (Activase), anistreplase
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
For thrombolytic therapy to be effective in treating
stroke or heart attack, prompt medical attention is very
important. The drugs must be given within a few hours
of the beginning of a stroke or heart attack. However,
this treatment is not right for every patient who has a
heart attack or a stroke. Only a qualified medical professional can decide whether a thrombolytic agent
should be used. To increase the chance of survival and
reduce the risk of serious, permanent damage, anyone
who has signs of a heart attack or stroke should get
immediate medical help.
Thrombolytic therapy may cause bleeding.
Usually this is not serious, but severe bleeding does
occur in some people. This is especially likely in older
people. To lower the risk of serious bleeding, people
who are given this drug should move around as little as
possible and should not try to get up on their own
unless told to do so by a health care professional.
Following all the instructions of the health care providers in charge is very important.
Thrombolytic therapy may be more likely to cause
serious bleeding in people who have certain medical
conditions or have recently had certain medical procedures. Before being given a thrombolytic agent, anyone with any of these problems or conditions should
tell the physician in charge about it:


blood disease or current or past bleeding problems in
any part of the body



heart or blood vessel disease



stroke (recent or in the past)



high blood pressure



brain tumor or other brain disease



stomach ulcer or colitis



severe liver disease



active tuberculosis
3689

Thrombolytic therapy

Prognosis

Thrombolytic therapy



recent falls, injuries, or blows to the body or head



recent injections into a blood vessel



recent surgery, including dental surgery



tubes recently placed in the body for any reason



recent delivery of a baby

KEY TERMS
Arteries—Blood vessels that carry blood away from
the heart to the cells, tissues, and organs of the
body.
Blood clot—A hard mass that forms when blood
gels.

In addition, anyone who has had a recent streptococcal (strep) infection should tell the physician in
charge. Some thrombolytic agents may not work
properly in people who have just had a strep
infection, so the physician may want to use a different
drug.

Chemotherapy—Treatment of an illness with chemical agents. The term is usually used to describe
the treatment of cancer with drugs.
Dialysis—A process used in people whose kidneys
are not working well. By way of a filtering machine,
dialysis separates waste and other useless materials
from the blood – a job the kidneys usually do.
Paralysis—Loss of the ability to move one or more
parts of the body.

People who take certain medicines may be at
greater risk for severe bleeding when they are given a
thrombolytic agent.
Women who are pregnant should tell the physician
in charge before being given a thrombolytic agent.
There is a slight chance that a woman who is given
thrombolytic therapy during the first five months of
pregnancy will have a miscarriage. However, streptokinase and urokinase have both been used without problems in pregnant women.
After being treated with thrombolytic therapy,
women who are breastfeeding should check with
their physicians before starting to breastfeed again.

Side effects
Anyone who has fever or who notices bleeding or
oozing from their gums, from cuts, or from the site
where the thrombolytic agent was injected should
immediately tell their health care provider.
People who are given thrombolytic therapy
should also be alert to the signs of bleeding inside the
body and should check with a physician immediately if
any of the following symptoms occur:


blood in the urine



blood or black, tarry stools



constipation



coughing up blood



vomiting blood or material that looks like coffee
grounds



nosebleeds



unexpected or unusually heavy vaginal bleeding



dizziness



sudden, severe, or constant headaches



Pain or swelling in the abdomen or stomach



back pain or backache

3690

Stroke—A serious medical event in which blood
flow to the brain is stopped. This may be because of
a blood clot in an artery or because an artery has
burst. Strokes may cause paralysis and changes in
speech, memory, and behavior.



severe or constant muscle pain or stiffness



stiff, swollen, or painful joints

Other side effects of thrombolytic agents are possible. Anyone who has unusual symptoms during or
after thrombolytic therapy should tell a health care
professional.

Interactions
People who take certain medicines may be at
greater risk for severe bleeding when they receive a
thrombolytic agent. Anyone who is given a thrombolytic agent should tell the physician in charge about all
other prescription or nonprescription (over-the-counter) medicines he or she is taking. Among the medicines that may increase the chance of bleeding are:


aspirin and other medicines for pain and inflammation



blood thinners (anticoagulants)



antiseizure medicines, such as Depakote (divalproex)
and Depakene (valproic acid)



cephalosporins, such as cefamandole (Mandol),
cefoperazone (Cefobid), and Cefotetan (Cefotan)

Also, anyone who has been treated with anistreplase or streptokinase within the past year should tell
the physician in charge. These drugs may not work
GALE ENCYCLOPEDIA OF MEDICINE

Nancy Ross-Flanigan

Thrombophlebitis
Definition
Thrombophlebitis is the inflammation of a vein
with blood clot formation inside the vein at the site of
the inflammation. Thrombophlebitis also is known as
phlebitis, phlebothrombosis, and venous thrombosis.

Description
There are two parts to thrombophlebitis, inflammation of a vein and blood clot formation. If the inflammation is minor, the disease usually is called venous
thrombosis or phlebothrombosis. Thrombophlebitis
can occur in both deep veins and superficial veins, but
most often occurs in the superficial veins of the extremities (legs and arms). Most cases occur in the legs.
When thrombophlebitis occurs in a superficial vein,
one that is near the surface of the skin and is visible to
the eye, the disease is called superficial thrombophlebitis. Any form of injury to a blood vessel can result in
thrombophlebitis. In the case of superficial thrombophlebitis, the blood clot usually attaches firmly to
the wall of the affected blood vein. Since superficial
blood veins do not have muscles that massage the
veins, blood clots in superficial veins tend to remain
where they form and seldom break loose. When
thrombophlebitis occurs in a deep vein, a vein that
runs deep within muscle tissue, it is called deep
venous thrombosis. Deep venous thrombosis presents the threat of producing blood clots that will
break loose to form emboli. These can lodge in
other tissues where they can block the blood supply,
typically in the lungs. This results in tissue damage
and can sometimes be serious or fatal, for example;
pulmonary embolism.

Causes and symptoms
The main symptoms are tenderness and pain in the
area of the affected vein. Redness and/or swelling also
may be seen. In the case of deep venous thrombosis,
there is more swelling than is caused by superficial
thrombophlebitis, and the patient may experience
GALE ENCYCLOPEDIA OF MEDICINE

muscle stiffness in the affected area. There are many
causes of thrombophlebitis.
The main causes can be grouped into three
categories; injury to blood veins, increased blood
clotting, and blood stasis. When blood veins are
damaged, collagen in the blood vein wall is
exposed. Platelets respond to collagen by initiating
the clotting process. Damage to a vein can occur as
a consequence of indwelling catheters, trauma,
infection, Buerger’s disease, or the injection of irritating substances. Increased tendency of the blood
to clot can be caused by malignant tumors, genetic
disorders, and oral contraceptives, though newer
generation birth control pills carry a lower risk
for many women. Stasis, in which the blood clots
due to decreased blood flow in an area, can happen following surgery, as a consequence of varicose
veins, as a complication of postpartum states, and
following prolonged bed rest. In the case of prolonged bed rest, blood clots form because of inactivity, which allows blood to move sluggishly and
stagnate (collect) in blood veins. This can lead to
blood clots. These clots (also called emboli) sometimes are released when the patient stands up and
resumes activity. This can present a problem if the
emboli lodge in vital organs. In the case of postpartum patients, a fever developing four to 10 days
after delivery may indicate thrombophlebitis. A
2004 study revealed that postmenopausal women
taking hormone therapy combining estrogen and
progestin had more than a twofold higher risk of
venous thrombosis than non-hormone users.

Diagnosis
In superficial thrombophlebitis, the location of
the clot sometimes can be seen by the unaided eye.
Blood clots are hard and can usually be detected by a
physician using palpation (touching or massage).
Deep venous thrombosis requires specialized diagnostic procedures to detect the blood clot. Among the
exams a physician may use are ultrasound and x ray,
coupled with dye injection (venogram).

Treatment
Superficial thrombophlebitis usually resolves
without treatment. If treatment of superficial
thrombophlebitis is given, it usually is limited to
the application of heat or anti-inflammatory drugs,
like aspirin or ibuprofen, which also help to relieve
the pain. It can take from several days to several
weeks for the clot to resolve and the symptoms to
completely disappear. A 2003 study showed that
3691

Thrombophlebitis

properly if they are given again, so the physician may
want to use a different thrombolytic agent.

Thymoma

KEY TERMS
Emboli, embolus—Emboli is the plural form of
embolus. Embolus is any mass of air, blood clot, or
foreign body that travels through the blood stream
and is capable of lodging in smaller blood vessels
where they obstruct the blood flow to that vessel.
Embolism—The obstruction of a blood vessel by a
blot clot.
Phlebitis—Inflammation of a vein.
Thrombus—A blood clot that forms within a blood
vessel or the heart.

low intensity therapy with warfarin, a common
blood thinner, prevented recurrent venous thromboembolism in study subjects. A newer anticoagulant called ximelagatran also has been shown as
equally or more effective than warfarin in preventing deep vein thrombosis.
Deep venous thrombosis is a serious condition,
treated with anticoagulant drugs and by keeping
the affected limb elevated. The primary objective in
treating deep venous thrombosis is prevention of a
pulmonary embolism. The patient usually is hospitalized during initial treatment. The prescribed anticoagulant drugs limit the ability of blood clots to
grow and new clots to form. Sometimes, a drug that
dissolves blood clots is administered. These drugs
must be used with caution because, as the clot dissolves, it may release from the site where it formed
and become an embolus. Surgery may be used if the
affected vein is likely to present a long–term threat of
producing blood clots that will release emboli. When
superficial thrombophlebitis occurs in the groin,
where the superficial veins join the deep veins, the
threat of emboli is present. In this case, blood clots
formed in the superficial veins can extend into the
much larger deep vein where they break off and are
released into the blood stream. The affected veins are
either removed or tied off to prevent the release of the
blood clots. Tying off superficial blood veins is an
outpatient procedure that can be performed with
local anesthesia. The patient is capable of immediately
resuming normal activities.

Prognosis
Superficial thrombophlebitis seldom progresses
to a serious medical complication, although non-lethal
embolisms may be produced. Deep venous thrombosis
3692

may lead to embolism, especially pulmonary embolism. This is a serious consequence of deep venous
thrombosis, and sometimes is fatal.
Resources
PERIODICALS

Brunk, Doug. ‘‘Thrombosis Risk Doubled in Women on
Combo HT: Data from WHI Study: Risk Increases
With Age, Body Mass Index.’’ Internal Medicine News
January 15, 2004: 1–3.
Elliott, William T. ‘‘Warfarin Effectively Prevents Venous
Thromboembolism.’’ Clinical Cardiology Alert April
2003: 1–2.
‘‘Registrat: The Combined Pill, Part One.’’ GP September 8,
2003: 46.
‘‘WPrevention of VTE With Ximelagatran.’’ Neurology
Alert February 2004: SS3–SS5.

John T. Lohr, PhD
Teresa G. Odle

Thrush see Candidiasis
Thymol see Antiseptics

Thymoma
Definition
Thymomas are the most common tumor of the
thymus.

Description
The thymus is located in the upper chest just
below the neck. It is a small organ that produces
certain types of white blood cells before birth and
during childhood. These white blood cells are called
lymphocytes and are an important part of the bodyôs
immune system. Once released from the thymus, lymphocytes travel to lymph nodes where they help to
fight infections. The thymus gland becomes smaller
in adulthood and is gradually taken over by fat tissue.
Although rare, thymomas are the most common
type of thymic cancer. They arise from thymic epithelial cells, which make up the covering of the thymus.
Thymomas frequently contain lymphocytes, which are
noncancerous. Thymomas are classified as either noninvasive (previously called ‘‘benign’’) or invasive (previously called ‘‘malignant’’). Noninvasive thymomas
are those in which the tumor is encapsulated and easy
to remove. Invasive thymomas have spread to nearby
GALE ENCYCLOPEDIA OF MEDICINE

diseases. Thymomas can be identified by chest x ray,
magnetic resonance imaging, and computed
tomography.

Thymoma affects men and women equally. It is
usually diagnosed between the ages of 40 and 60 years.
Thymomas are uncommon in children.

A biopsy may be performed, in which a small
sample of the tumor is removed and examined under
the microscope. However, because of the risk of ‘‘seeding’’ cancerous cells, biopsies are not routinely performed. There are a few different methods to biopsy a
thymoma. For a mediastinoscopy, a wand-like lighted
camera (endoscope) and special instruments are
passed through a small cut in the lower neck. The
surgeon can see the tumor on a monitor and can cut
off small samples for microscopic analysis.
Mediastinoscopy is performed under general anesthesia. Alternatively, a needle biopsy will be taken in
which a long needle is passed through the skin and
into the tumor. Fine needle biopsy uses a thin needle
and larger-core needle biopsy uses a wider needle.
Needle biopsies may be performed in conjunction
with CT imaging.

Causes and symptoms
The cause of thymoma is unknown. Cancer is
caused when the normal mechanisms that control cell
growth become disturbed, causing the cells to continually grow without stopping. This is caused by
damage to the DNA in the cell.
Approximately 40% of the patients diagnosed
with thymoma have no symptoms. The symptoms in
the remaining 60% of patients are caused by pressure
from the enlarged thymus on the windpipe (trachea) or
blood vessels, or by paraneoplastic syndromes.
Paraneoplastic syndromes are collections of symptoms in cancer patients that cannot be explained by
the tumor. Seventy-one percent of thymomas are associated with paraneoplastic syndromes. The most common syndromes related to thymoma are pure red cell
aplasia (having abnormally low levels of red blood
cells), myasthenia gravis (a muscular disorder), and
hypogammaglobulinemia (having abnormally low
levels of antibodies). These conditions are autoimmune diseases—those in which the body mounts an
attack against certain normal cells of the body.
Symptoms of thymoma may include:


shortness of breath



swelling of the face



coughing



chest pain



muscle weakness (especially in the eyes, neck, and
chest, causing problems with vision, swallowing, and
breathing)



weakness



dizziness



shortness of breath



fatigue

Patients who are having difficulty breathing may
have a bronchoscopy performed to examine the wind
pipe. An endoscope, in this case a bronchoscope, is
inserted through the mouth and into the windpipe.
The physician will look for tumors and may perform
biopsies.

Treatment
Clinical staging
There is more than one type of staging system for
thymoma; but the Masaoka system, a surgical staging
system developed in 1981, is used most often.
Thymoma is categorized into four stages (I, II, III,
and IV), which may be further subdivided (A and B)
based on the spread of cancerous tissue. The Masaoka
staging system is as follows:


Stage I. The thymoma lies completely within the
thymus.



Stage II. The thymoma has spread out of the thymus
and invaded the outer layer of the lung (pleura) or
nearby fatty tissue.



Stage III. The thymoma has spread to other neighboring tissues of the upper chest, including the outer
layer of the heart (pericardium), the lungs, or the
heartôs main blood vessels.



Stage IVA. The thymoma has spread throughout the
pericardium and/or the pleura.



Stage IVB. The thymoma has spread to organs in
other parts of the body.

Diagnosis
The physician will conduct a complete physical
exam. He or she may be able to feel a fullness in the
lower neck region. Routine blood tests may be performed. Imaging studies are necessary because the
symptoms of thymoma can be caused by many other
GALE ENCYCLOPEDIA OF MEDICINE

3693

Thymoma

structures (such as the lungs) and are difficult to
remove. Approximately 30% to 40% of thymomas
are of the invasive type.

Thymoma

In 1999, the World Health Organization (WHO)
adopted a new classification system for thymic
tumors. This system is a histologic classification,
which means that it is based on the microscopic features of the cells that make up the tumor. The WHO
classification system ranks thymomas into types A,
AB, B1, B2, B3, and C, by increasing severity.
The treatment for thymoma depends on the stage
of cancer and the patients overall health. Because
thymomas are so rare, there are no defined treatment
plans. Treatment options include surgery, radiation
therapy, and/or chemotherapy. Surgical removal of
the tumor is the preferred treatment. Surgery is often
the only treatment required for stage I tumors.
Treatment of thymoma often relieves the symptoms
caused by paraneoplastic syndromes.
A treatment that is intended to aid the primary
treatment is called adjuvant therapy. For instance,
chemotherapy may be used along with surgery to
treat thymoma. Stages II, III, and IV thymomas are
often treated with surgery and some form of adjuvant
therapy.
Surgery
Thymoma may be treated by surgically removing
(resecting) the tumor and some of the nearby healthy
tissue. Removal of the entire thymus gland is called a
thymectomy. Surgery on the thymus is usually performed through the chest wall by splitting open the
breast bone (sternum), a procedure called a median
sternotomy. When complete removal of the tumor is
impossible, the surgeon will remove as much of the
tumor as possible (debulking surgery, subtotal resection). In these cases, If the tumor has spread, surgery
may include removal of such other tissues as the
pleura, pericardium, blood vessels of the heart, lung,
and nerves.
Radiation therapy
Radiation therapy uses high-energy radiation
from x rays and gamma rays to kill the cancer cells.
Radiation given from a machine that is outside the
body is called external radiation therapy. Radiation
therapy is often used as adjuvant therapy following
surgery to reduce the chance of cancer recurrence.
Radiation may be used to kill cancer cells in cases in
which the tumor was only partially removed. It may be
used before surgery to shrink a large tumor. Radiation
therapy is not very effective when used alone, although
it may be used alone when the patient is too sick to
withstand surgery.
3694

The skin in the treated area may become red and dry
and may take as long as a year to return to normal.
Radiation to the chest may damage the lung, causing
shortness of breath and other breathing problems. Also,
the tube that goes between the mouth and stomach
(esophagus) may be irritated by radiation, causing swallowing difficulties. Fatigue, upset stomach, diarrhea, and
nausea are also common complaints of patients having
radiation therapy. Most side effects go away about two
to three weeks after radiation therapy has ended.
Chemotherapy
Chemotherapy uses anticancer drugs to kill the cancer cells. The drugs are given by mouth (orally) or
intravenously. They enter the bloodstream and can travel to all parts of the body. Chemotherapy may be given
before surgery to shrink a tumor, which is called neoadjuvant therapy. Thymoma cells are very sensitive to
anticancer drugs, especially cisplatin, doxorubicin, and
ifosfamide. Generally, a combination of drugs is given
because it is more effective than a single drug in treating
cancer. Corticosteroids are also used to treat thymoma.
The side effects of chemotherapy are significant,
and include stomach upset, vomiting, appetite loss, hair
loss (alopecia), mouth sores, and fatigue. Women may
experience vaginal sores, menstrual cycle changes, and
premature menopause. There is also an increased chance
of infections.

Alternative treatment
Although alternative and complementary therapies are used by many cancer patients, very few controlled studies on the effectiveness of such therapies
exist. Mind-body techniques such as prayer, biofeedback, visualization, meditation, and yoga, have not
shown any effect in reducing cancer; but they can
reduce stress and lessen some of the side effects of
cancer treatments. Gerson, macrobiotic, orthomolecular, and Cancell therapies are ineffective treatments
for cancer.
Clinical studies of hydrazine sulfate found that it
had no effect on cancer and even worsened the health
and well-being of the study subjects. One clinical
study of the drug amygdalin (Laetrile) found that it
had no effect on cancer. Laetrile can be toxic and has
caused deaths. Shark cartilage has been studied as a
cancer treatment and is presently being studied by the
FDA in clinical trials. Although the results are mixed,
clinical studies suggest that melatonin may increase
the survival time and quality of life for cancer
patients.
GALE ENCYCLOPEDIA OF MEDICINE

Adjuvant therapy—A treatment that is intended to
aid the primary treatment. Adjuvant treatments for
thymic cancer are radiation therapy and
chemotherapy.
Invasive—A descriptive term for thymoma that has
spread beyond the outer wall of the thymus.
Lymphocyte—A type of white blood cell that is
found in the thymus.
Neoadjuvant therapy—Radiation therapy or chemotherapy used to shrink a tumor before surgical
removal of the tumor.
Paraneoplastic syndrome—A set of symptoms that
is associated with cancer but is not directly caused
by the cancer.
Pleura—The outer covering of the lungs.

BOOKS

Bruss, Katherine, Salter, Christing, and Esmeralda Galan,
editors. American Cancer Society+s Guide to
Complementary and Alternative Cancer Methods.
Atlanta: American Cancer Society, 2000.
Cameron, Robert, Loehrer, Patrick, and Charles Thomas.
‘‘Neoplasms of the Mediastinum.’’ In Cancer:
Principles & Practice of Oncology, edited by Vincent
DeVita, Hellman, Samuel, and Steven Rosenberg.
Philadelphia: Lippincott Williams & Wilkins, 2001,
pp.1019-36.
PERIODICALS

Giaccone, Giuseppe. ‘‘Treatment of Thymoma and Thymic
Carcinoma.’’ Annals of Oncology 11, Supplement 3
(2000): 245-6.
Muller-Hermelink, H., and A. Marx. ‘‘Thymoma.’’ Current
Opinion in Oncology 12 (September 2000): 426-33.
Thomas, Charles, Wright, Cameron, and Patrick Loehrer.
‘‘Thymoma: State of the Art.’’ Journal of Clinical
Oncology 17 (July 1999): 2280-89.
ORGANIZATIONS

Selenium, in safe doses, may delay the progression
of cancer. Laboratory and animal studies suggest that
curcumin, the active ingredient of turmeric, has anticancer activity. Maitake mushrooms may boost the
immune system, according to laboratory and animal
studies. The results of laboratory studies suggest that
mistletoe has anticancer properties; however, clinical
studies have not been conducted.

American Cancer Society. 1599 Clifton Road NE, Atlanta,
GA 30329. (800) ACS-2345. <http://
www.cancer.org>.
Cancer Research Institute, National Headquarters. 681
Fifth Ave., New York, NY 10022. (800) 992-2623.
<http://www.cancerresearch.org>.
National Institutes of Health. National Cancer Institute.
9000 Rockville Pike, Bethesda, MD 20982. Cancer
Information Service: (800) 4-CANCER. <http://
cancernet.nci.nih.gov>.

Belinda Rowland, Ph.D.

Prognosis
The five-year survival rates for thymomas are
96% for stage I, 86% for stage II, 69% for stage III,
and 50% for stage IV. Thorough (radical) surgery is
associated with a longer survival rate. Almost 15% of
thymoma patients develop a second cancer.
Thymomas rarely spread (metastasize) outside of
the chest cavity. Metastasis is usually limited to the
pleura. Invasive thymomas are prone to recurrence,
even 10 to 15 years following surgery. The recurrence
rates are drastically reduced and the five-year survival
rates are drastically increased in patients who receive
adjuvant radiation therapy.

Prevention
Because there are no known risk factors for the
development of thymoma, there are no preventive
measures. However, there may be an association
between thymic cancer and exposure of the chest to
radiation.
GALE ENCYCLOPEDIA OF MEDICINE

Thymus tumor see Thymoma

Thyroid biopsy
Definition
The thyroid biopsy is a procedure in which a
sample of thyroid tissue is withdrawn for laboratory
examination. The sample can be withdrawn through a
needle or a surgical incision may be made to obtain a
piece of thyroid tissue.

Purpose
The test is generally performed when a lump or a
nodule is detected in the thyroid. The test may also be
ordered if the thyroid gland is enlarged and the cause is
3695

Thyroid biopsy

Resources

KEY TERMS

Thyroid biopsy

not apparent. The biopsy is usually a test for thyroid
cancer.

Precautions
A patient with a bleeding disorder should not have
a biopsy unless the bleeding problem can be corrected
by a transfusion of the cells that cause blood to clot
(platelets).

Description
The thyroid is a butterfly-shaped gland located at
the base of the neck. It produces thyroxine, a hormone
that plays a very crucial role in regulating the metabolism of the body and controlling several vital functions, such as the heart beat, blood pressure, and
body temperature. The thyroid also regulates childhood growth and development.
A thyroid biopsy is usually ordered when a painless lump or a nodule is detected, either by the patient
or by a doctor during a routine physical examination.
A biopsy is the only test that can accurately determine
whether the lump is non-cancerous (benign) or cancerous (malignant). The biopsy can be performed in several ways.
The ‘‘fine needle aspiration’’ (FNA) can be done
in the doctor’s office. An anesthetic is not usually
given. The patient will be asked to lie on his or her
back. A pillow will be placed under the shoulders and
the neck will be extended. The biopsy site will be
cleansed with a sterile antiseptic solution. A thin needle will be inserted into the thyroid, and a sample of
thyroid cells and some fluid will be collected. The
needle will be quickly withdrawn. Pressure will be
applied at the biopsy site to stop the bleeding and a
bandage may be used to cover the area. The test takes
three to five minutes.
For ‘‘large needle biopsy,’’ a mild sedative may be
given an hour before the procedure, to relax the
patient. The patient will be asked to lie on his or her
back, with the head tipped back and the neck
extended. The biopsy site will be thoroughly cleansed
and the physician will inject a local anesthetic. A small
incision (about 1 inch) will be made in the skin. The
biopsy needle will be inserted through the incision into
the thyroid. A sample of tissue will be removed and the
needle withdrawn. Pressure is applied at the biopsy site
to stem the bleeding and a bandage applied. This test
takes five to ten minutes.
The ‘‘open incisional biopsy’’ is done in an operating room by a surgeon. The patient will be given a
general anesthetic. A sedative will be given an hour
3696

before the procedure to relax the patient. An intravenous line will be placed in the arm for infusion of fluids
or drugs. An endotracheal tube will be inserted
through the mouth into the lungs for administering
anesthetic gases. After the patient is anesthetized, a
small incision is made in the neck. Either the whole
thyroid or a part of it is removed. If only a portion is
being removed, the surgeon may send a small piece of
remaining tissue to the laboratory for immediate testing while the patient is still on the operating table. If
the pathologist’s report comes back stating that cancer
is present in the remaining tissue, the entire thyroid is
removed. The incision is closed with stitches. The
whole procedure may take about an hour.

Preparation
The doctor should be informed of any allergies to
medications and every medication the patient is taking.
If the patient is pregnant, the doctor should be told.
The patient will be asked to sign the necessary
consent forms. If a needle biopsy is done, no special
preparation is needed. If a large needle biopsy is being
done, the doctor may order some tests to determine
the clotting ability of the blood. If an open incisional
biopsy is being done, a general anesthetic is required
and the patient will be asked to refrain from eating or
drinking anything 8-12 hours before the test.

Aftercare
The needle used in fine needle aspiration is so thin,
the whole procedure feels like a quick injection. There is
no pain or tenderness at the site after the test. In large
needle biopsy, a stinging needle prick may be felt when
the local anesthetic is injected. The site may be sore for a
few hours and tender for a day or two after the test.
In the open incisional biopsy, the patient will feel
nothing during the procedure, because of the effects of
the anesthetic and the sedative. However, the anesthetic may cause the patient to feel drowsy for several
hours after the procedure. The anesthetic may also
cause the patient to experience some fatigue, and general aches and pains for a day or two after the procedure. The endotracheal tube may make the throat feel
mildly sore. If there is swelling at the biopsy site or if
the patient develops a fever, the doctor should be
notified immediately.

Risks
No risks are associated with fine needle aspiration. Large needle biopsy may cause bleeding into the
GALE ENCYCLOPEDIA OF MEDICINE

Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Endotracheal tube—A hollow tube that is inserted
into the windpipe (trachea), leading to the lungs.
Pathologist—A doctor who specializes in the diagnosis of disease by studying cells and tissues under
a microscope.

thyroid gland. There is a small risk that the anesthetic
used in open surgical biopsy may cause a life-threatening reaction.

Normal results
The normal appearance and architecture of the
thyroid cells indicate that no cancer cells are present
in the thyroid tissue.

Abnormal results
Any abnormalities of the thyroid tissue cells may
indicate cancer benign tumors, or some other thyroid
disease. If cancer is suspected, the pathologist may do
some more testing to identify the extent of the cancer,
so that it can be treated appropriately.
Resources
ORGANIZATIONS

American Thyroid Association, Inc. Montefiore Medical
Center, 111 East 210th St., Bronx, NY 10467. <http://
thyroid.org>.
Thyroid Foundation of America, Inc. Ruth Sleeper Hall,
RSL 350, 40 Parkman St., Boston, MA 02114-2698.
(800) 832-8321.

Lata Cherath, PhD

Thyroid cancer
Definition
Thyroid cancer is a disease in which the cells of the
thyroid gland become abnormal, grow uncontrollably, and form a mass of cells called a tumor.
GALE ENCYCLOPEDIA OF MEDICINE

Thyroid cancer is grouped into four types
based on how its cells appear under a microscope.
The types are papillary, follicular, medullary and
anaplastic thyroid cancers. They grow at different
rates and can spread to other parts of the body if
left untreated.
The thyroid is a hormone-producing butterflyshaped gland located in the neck at the base of
the throat. It has two lobes, the left and the right.
The thyroid uses iodine, a mineral found in some
foods, to make several of its hormones. Thyroid hormones regulate essential body processes such as
heart rate, blood pressure, body temperature, metabolism; and affect the nervous system, muscles and
other organs. These hormones also play an important role in regulating childhood growth and
development.
Diseases of the thyroid gland affect millions
of Americans. The most common diseases of the
thyroid are either hyperthyroidism (Graves’ disease)
or hypothyroidism, an overactive or an underactive
gland, respectively. Sometimes lumps or masses may
develop in the thyroid, and although most (ninety-five
percent) of these lumps or nodules are noncancerous
(benign), all thyroid lumps should be taken seriously.
The American Cancer Society estimates that the
approximately 17,200 new cases of thyroid cancer
that occur in the United States account for 1% of all
cancers.
Women are three times more likely to develop
thyroid cancer than men. Although the disease affects
teenagers and young adults, most people that develop
thyroid cancer are over 50 years of age.

Causes and symptoms
The exact cause of thyroid cancer is not known;
but it is more common in whites than in African
Americans. Radiation was used in the 1950s and
1960s to treat acne and to reduce swelling in infections
of the tonsils, adenoids and lymph nodes. It has been
proven that this exposure is a risk factor for thyroid
cancer. In some areas of the world, diets are low in
iodine. Papillary and follicular cancers occur more
frequently in these areas. Iodine deficiency is not a
large problem in the United States because iodine is
added to table salt and other foods. Approximately
7% of thyroid cancer are caused by the alteration
(mutation) of a gene called the RET gene, which can
be inherited.
3697

Thyroid cancer

Description

KEY TERMS

Thyroid cancer

Symptoms are rare so the lump is not usually
painful. The symptoms of thyroid nodules are:


a lump or nodule that can be felt in the neck is the
most frequent sign of thyroid cancer



the lymph nodes may be swollen and the voice may
become hoarse because the tumor presses on the
nerves leading to the voice box



some patients experience a tight or full feeling in the
neck and have difficulty breathing or swallowing

Diagnosis
Physicians use several tests to confirm the suspicion of thyroid cancer, to identify the size and location
of the lump and to determine whether the lump is noncancerous (benign) or cancerous (malignant). Blood
tests such as the thyroid stimulating hormone (TSH)
test check thyroid function. These are drawn by a
technician with a needle and takes a few minutes. It
take several days to be interpreted by a pathologist.
Calcitonin is produced by the C cells (parafollicular
cells) of the thyroid gland when the parafollicular cells
of the thyroid become cancerous. Blood calcitonin
levels are used to confirm the diagnosis of medullary
thyroid cancer if it is suspected.
Computed tomography scan (CT scan) or an
ultrasonography (ultrasound scan) are imaging tests
used to produce a picture of the thyroid and usually
last less than one hour. A radiologist usually interprets
the results within 24 hours. In ultrasonography, highfrequency sound waves are bounced off the thyroid.
The pattern of echoes that is produced by these waves
is converted into a computerized image on a television
screen. This test can determine whether the lumps
found in the thyroid are benign fluid-filled cysts or
solid malignant tumors.
A radioactive scan may take several hours and can
be used to identify any abnormal areas in the thyroid
by giving the patient a very small amount of radioactive iodine, which can either be swallowed or
injected into the thyroid. Since the thyroid is the only
gland in the body that absorbs iodine, the radioactive
iodine accumulates there. An x-ray image can then be
taken or an instrument called a ‘‘scanner’’ can be used
to identify areas in the thyroid that do not absorb
iodine normally. These abnormal spots are called
‘‘cold spots’’ and further tests are performed to check
whether the cold spots are benign or malignant
tumors. If a significant amount of radioactive iodine
is concentrated in the nodule, then it is termed ‘‘hot’’
and is usually benign. Again a radiologist interprets
the results within a day.
3698

A gamma scan of the human thyroid gland revealing cancer.
(Custom Medical Stock Photo. Reproduced by permission.)

The most accurate diagnostic tool for thyroid
cancer is a biopsy. In this process a sample of thyroid
tissue is withdrawn and examined under a microscope
by a pathologist. This usually takes a day or so. The
tissue samples can be obtained either by drawing out a
sample of tissue through a needle (needle biopsy) or by
surgical removal of the nodule (surgical biopsy). A
needle biopsy takes a few minutes and can be done
by any trained physician, usually a radiologist. The
surgical biopsy is done by a surgeon under general
anesthesia with the help of an anesthesiologist and
will take a few hours. If thyroid cancer is diagnosed,
further tests may be done to learn about the stage of
the disease and help doctors plan appropriate
treatment.

Treatment
The aggressiveness of each type of thyroid cancer
is different. Cancer staging considers the size of the
tumor, whether it has grown into surrounding lymph
nodes and whether it has spread to distant parts of the
body (metastasized). Age and general health status are
also taken into account. In patients less than 45 years
old there are only two stages. I papillary or follicular
type thyroid cancer, stage I refers to patients without
evidence of cancer that has spread to the body. Stage II
refers to patients with spread of cancer outside the
thyroid gland. In patients over 45, patients with
tumors smaller than one cm are classified as stage I,
those with tumors not broken through the capsule
(covering) of the thyroid belong to stage II, those
with tumors outside the capsule or lymph node involvement are called stage III and those with spread outside the thyroid area are stage IV. In medullary–type
thyroid cancer, stage I and IV are the same. Stage II
GALE ENCYCLOPEDIA OF MEDICINE

The papillary type (60–80% of all thyroid cancers)
is a slow-growing cancer that develops in the hormone-producing cells (that contain iodine) and can
be treated successfully. The follicular type (30–50%
of thyroid cancers) also develops in the hormone-producing cells, has a good cure rate but may be difficult
to control if the cancer invades blood vessels or grows
into nearby structures in the neck. The medullary type
(5–7% of all thyroid cancers) develops in the parafollicular cells (also known as the C cells) that produce
calcitonin, a hormone that does not contain iodine.
Medullary thyroid cancers are more difficult to control because they often spread to other parts of the
body. The fourth type of thyroid cancer, anaplastic
(2% of all thyroid cancers), is the fastest-growing and
is usually fatal because the cancer cells rapidly spread
to the different parts of the body.
More than 90% of patients who are treated for
papillary or follicular cancer will live for 15 years or
longer after the diagnosis of thyroid cancer. Eighty
percent of patients with medullary thyroid cancer will
live for at least 10 years after surgery. Only 3–17% of
patients with anaplastic cancer survive for five years.
Like most cancers, cancer of the thyroid is best
treated when it is found early by a primary physician.
Treatment depends on the type of cancer and its stage.
Four types of treatment are used: surgical removal,
radiation therapy, hormone therapy and chemotherapy. Surgical removal is the usual treatment if the
cancer has not spread to distant parts of the body.
The surgeon may remove the side or lobe of the
thyroid where the cancer is found (lobectomy) or all
of it (total thyroidectomy). If the adjoining lymph
nodes are affected, they may also be removed during
surgery. When the thyroid gland is removed and
levels of thyroid hormones decrease, the pituitary
gland starts to produce TSH that stimulates the thyroid cells to grow.
A radiation-oncologist uses radiation therapy
with high-energy x-rays to kill cancer cells and
shrink tumors. The radiation may come from a
machine outside the body (external beam radiation), or the patient may be asked to swallow a
drink containing radioactive iodine. Because the
thyroid cells take up iodine, the radioactive iodine
collects in any thyroid tissue remaining in the body
and kills the cancer cells. A hematologist-oncologist uses chemotherapy either as a pill or an injection through a vein in the arm.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic
purposes.
Calcitonin—A hormone produced by the parafollicular cells (C cells) of the thyroid. The main function of the hormone is to regulate calcium levels in
body serum.
Chemotherapy—Treatment of cancer with synthetic drugs that destroy the tumor either by inhibiting the growth of the cancerous cells or by killing
them.
Hormone therapy—Treatment of cancer by inhibiting the production of hormones such as testosterone and estrogen.
Hyperthyroidism—A condition in which the thyroid is overactive due to overstimulation of the thyroid cells.
Hypothyroidism—A condition in which the thyroid gland is underactive.
Lobectomy—A surgical procedure that removes
one lobe of the thyroid.
Radiation therapy—Treatment with high-energy
radiation from x-ray machines, cobalt, radium, or
other sources.
Total thyroidectomy—A surgical procedure that
removes the entire thyroid gland.

Alternative treatment
Hormone therapy uses hormones after surgery to
stop this growth and the formation of new cancerous
thyroid cells. To prevent cancerous growth, the natural hormones that are produced by the thyroid are
taken in the form of pills. Thus, their levels remain
normal and inhibit the pituitary gland from making
TSH. If the cancer has spread to other parts of the
body and surgery is not possible, hormone treatment
is aimed at killing or slowing the growth of cancer cells
throughout the body.
A powerful phytochemical, lycopene, gives tomatoes their red color and appears to act as an antioxidant
in the body, repairing damaged cells and scavenging
free radicals, the molecules responsible for most types
of degenerative diseases and aging. Antioxidants such
as lycopene help inhibit DNA oxidation, which can
lead to certain forms of cancer. Lycopene is a normal
constituent of human blood and tissues, where it is
3699

Thyroid cancer

consists of patients with tumors greater than one cm
and stage III comprises patients with lymph node
involvement.

Thyroid function tests

found in greater concentrations than beta-carotene or
any other carotenoid. Tomatoes, including cooked or
processed tomatoes, tomato juices, soups, sauces, paste
and ketchup, contain more lycopene than any other
food. Guava, rose hip, watermelon and grapefruit
also contain lycopene.
Other antioxidants are: vitamin E (Dosage: 400 IU
daily), vitamin C (Dosage: 1,000 to 4,000 mg daily),
beta carotene (Dosage: 15 mg (25,000 IU) daily), lutein
(Dosage: 6 to 20 mg daily), pycnogenol (Dosage: 25
to 50 mg daily), green tea (Dosage: 300 to 400 mg
of green tea polyphenols daily), grape-seed extract
(Dosage: 100 mg daily), alpha lipoic acid (Dosage: 50
to 200 mg daily), N-acetylcysteine (Dosage: 600 mg
daily) and selenium (Dosage: 200 to 400 mcg daily).
Pregnant women should consult a physician before
taking any medication.

Prevention
Because most people with thyroid cancer have no
known risk factor, it is not possible to completely prevent this disease. However, inherited cases of medullary
thyroid cancer can be prevented and radiation to the
neck is avoided. If a family member has had this disease,
the rest of the family can be tested and treated early. The
National Cancer Institute recommends that a doctor
examine anyone who has received radiation to the head
and neck during childhood at intervals of one or two
years. The neck and the thyroid should be carefully
examined for any lumps or enlargement of the nearby
lymph nodes. Ultrasound may also be used to screen for
the disease in people at risk for thyroid cancer.
Resources
ORGANIZATIONS

National Cancer Institute (National Institutes of Health).
9000 Rockville Pike, Bethesda, MD 20892. (800)
422-6237. <http://www.nci.nih.gov>.

test (TSH), the thyroxine test (T4), the triiodothyronine test (T3), the thyroxine-binding globulin test
(TBG), the triiodothyronine resin uptake test
(T3RU), and the long-acting thyroid stimulator test
(LATS).

Purpose
Thyroid function tests are used to:


help diagnose an underactive thyroid (hypothyroidism) and an overactive thyroid (hyperthyroidism)



evaluate thyroid gland activity



monitor response to thyroid therapy

Precautions
Thyroid treatment must be stopped one month
before blood is drawn for a thyroxine (T4) test.
Steroids, propranolol (Inderal), cholestyramine
(Questran), and other medications that may influence
thyroid activity are usually stopped before a triiodothyronine (T3) test.
Estrogens, anabolic steroids, phenytoin, and thyroid medications may be discontinued prior to a thyroxine-binding globulin (TBG) test. The laboratory
analyzing the blood sample must be told if the patient
cannot stop taking any of these medications. Some
patients will be told to take these medications as
usual so that the doctor can determine how they affect
thyroxine-binding globulin.
Patients are asked not to take estrogens, androgens, phenytoin (Dilantin), salicylates, and thyroid
medications before having a triiodothyronine resin
uptake (T3RU) test.
Prior to taking a long-acting thyroid stimulant
(LATS) test, the patient will probably be told to stop
taking all drugs that could affect test results.

Kulbir Rangi, DO

Description

Thyroid drugs see Thyroid hormones

Thyroid function tests
Definition
Thyroid function tests are blood tests used to
evaluate how effectively the thyroid gland is working.
These tests include the thyroid-stimulating hormone
3700

Most doctors consider the sensitive thyroid-stimulating hormone (TSH) test to be the most accurate
measure of thyroid activity. By measuring the level of
TSH, doctors can determine even small problems in
thyroid activity. Because this test is sensitive, abnormalities in thyroid function can be determined before a
patient complains of symptoms.
TSH ‘‘tells’’ the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3).
Before TSH tests were used, standard blood tests measured levels of T4 and T3 to determine if the thyroid
GALE ENCYCLOPEDIA OF MEDICINE

The thyroxine-binding globulin (TBG) test measures blood levels of this substance, which is manufactured in the liver. TBG binds to T3 and T4, prevents
the kidneys from flushing the hormones from the
blood, and releases them when and where they are
needed to regulate body functions.
The triiodothyronine resin uptake (T3RU) test
measures blood T4 levels. Laboratory analysis of this
test takes several days, and it is used less often than
tests whose results are available more quickly.
The long-acting thyroid stimulator (LATS) test
shows whether blood contains long-acting thyroid stimulator. Not normally present in blood, LATS causes
the thyroid to produce and secrete abnormally high
amounts of hormones.

Thyroid function tests

gland was working properly. The triiodothyrine (T3)
test measures the amount of this hormone in the
blood. T3 is normally present in very small amounts,
but has a significant impact on metabolism. It is the
active component of thyroid hormone.

T4
Normal T4 levels are:


10.1–2.0 ug/dl at birth



7.5–16.5 ug/dl at one to four months



5.5–14.5 ug/dl at four to 12 months



5.6–12.6 ug/dl at one to six years



4.9–11.7 ug/dl at 10 years



4–11 ug/dl at 10 years and older.

Levels of free T4 (thyroxine not attached to TBG)
are higher in teenagers than in adults.
Normal T4 levels do not necessarily indicate normal thyroid function. T4 levels can register within
normal ranges in a patient who:


is pregnant



has recently had contrast x rays



has nephrosis or cirrhosis
T3

It takes only minutes for a nurse or medical
technician to collect the blood needed for these
blood tests. A needle is inserted into a vein, usually
in the forearm, and a small amount of blood is collected and sent to a laboratory for testing. The
patient will usually feel minor discomfort from the
‘‘stick’’ of the needle.

Normal T3 levels are:


90–170 ng/dl at birth



115–190 ng/dl at six to12 years



110–230 ng/dl in adulthood
TBG
Normal TBG levels are:

Preparation
There is no need to make any changes in diet
or activities. The patient may be asked to stop
taking certain medications until after the test is
performed.

Aftercare
Warm compresses can be used to relieve swelling
or discomfort at the site of the puncture. With a doctor’s approval, the patient may start taking medications stopped before the test.

Normal results



1.5–3.4 mg/dl or 15–34 mg/L in adults



2.9–5.4 mg/dl or 29–54 mg/L in children.
T3RU

Between 25% and 35% of T3 should bind to or be
absorbed by the resin added to the blood sample. The
test indirectly measures the amount of thyroid binding
globulin (TBG) and thyroid-binding prealbumin
(TBPA) in the blood.
LATS
Long-acting thyroid stimulator is found in the
blood of only 5% of healthy people.

Not all laboratories measure or record thyroid
hormone levels the same way. Each laboratory will
provide a range of values that are considered normal
for each test. Some acceptable ranges are listed below.

Abnormal results
T4
Elevated T4 levels can be caused by:

TSH



acute thyroiditis

Normal TSH levels for adults are 0.5–5.0 mU/L.



birth control pills

GALE ENCYCLOPEDIA OF MEDICINE

3701

Thyroid function tests



clofibrate (Altromed-S)



hypothyroidism



contrast x rays using iodine



kidney or liver disease



estrogen therapy



starvation



heparin



heroin

Decreased T3 levels can also be caused by
using:



hyperthyroidism



anabolic steroids



pregnancy



androgens



thyrotoxicosis



phenytoin



toxic thyroid adenoma



propranolol



reserpine (Serpasil)



salicylates in high doses

Cirrhosis and severe non-thyroid disease can raise
T4 levels slightly.
Reduced T4 levels can be caused by:


anabolic steroids



androgens



antithyroid drugs



cretinism



hypothyroidism



kidney failure



lithium (Lithane, Lithonate)



myxedema



phenytoin



propranolol
T3

Although T3 levels usually rise and fall when
T4 levels do, T3 toxicosis causes T3 levels to rise
while T4 levels remain normal. T3 toxicosis is a
complication of:

TBG
TBG levels, normally high during pregnancy, are
also high in newborns. Elevated TBG levels can also
be symptoms of:


acute hepatitis



acute intermittent porphyria



hypothyroidism



inherited thyroid hormone abnormality
TBG levels can also become high by using:



anabolic steroids



birth control pills



anti-thyroid agents



clofibrate



estrogen therapy



phenytoin



Graves’ disease



salicylates in high doses



toxic adenoma



thiazides



toxic nodular goiter



thyroid medications



warfarin (Coumadin)

T3 levels normally rise when a woman is pregnant
or using birth-control pills. Elevated T3 levels can also
occur in patients who use estrogen or methadone or
who have:


certain genetic disorders that do not involve thyroid
malfunction

TBG levels can be raised or lowered by inherited
liver disease whose cause is unknown.
Low TBG levels can be a symptom of:


acromegaly



hyperthyroidism



acute hepatitis or other acute illness



thyroiditis



hyperthyroidism



t3 thyrotoxicosis



kidney disease



toxic adenoma



malnutrition



marked hypoproteinemia



uncompensated acidosis

Low T3 levels may be a symptom of:


acute or chronic illness

3702

GALE ENCYCLOPEDIA OF MEDICINE

Acidosis—A condition in which blood and tissues
are unusually acidic.
Acromegaly—A disorder in which growth hormone
(a chemical released from the pituitary gland in the
brain) causes increased growth in bone and soft tissue. Patients have enlarged hands, feet, noses, and
ears, as well as a variety of other disturbances
throughout the body.
Acute intermittent porphyria—An inherited disease
affecting the liver and bone marrow. The liver
overproduces a specific acid and the disease is
characterized by attacks of high blood pressure,
abdominal colic, psychosis, and nervous system
disorders.
Anabolic steroids—Protein-building compounds
used to treat certain anemias and cancers, strengthen
bones, and stimulate weight gain and growth.
Anabolic steroids are sometimes used to illegally
enhance athletic performance.
Cholestyramine (Questran)—A drug used to bind
with bile acids and prevent their reabsorption and
to stimulate fat absorption.
Cirrhosis—Progressive disease of the liver, associated with failure in liver cell functioning and
blood flow in the liver. Tissue and cells are damaged,
the liver becomes fibrous, and jaundice can result.
Clofibrate (Altromed-S)—Medication used to lower
levels of blood cholesterol and triglycerides.
Cretinism—Severe hypothyroidism that is present
at birth and characterized by severe mental
retardation.
Graves’ disease—The most common form of
hyperthyroidism, characterized by bulging eyes,
rapid heart rate, and other symptoms.
Heparin—An organic acid that occurs naturally in
the body and prevents blood clots. Heparin is also
made synthetically and can be given as a treatment
when required.
Hepatitis—Inflammation of the liver.
Hyperthyroidism—Overactive thyroid gland; symptoms include irritability/nervousness, muscle weakness, tremors, irregular menstrual periods, weight
loss, sleep problems, thyroid enlargement, heat

GALE ENCYCLOPEDIA OF MEDICINE

sensitivity, and vision/eye problems. The most common type of this disorder is called Graves’ disease.
Hypoproteinemia—Abnormally low levels of protein in the blood.
Hypothyroidism—Underactive
thyroid
gland;
symptoms include fatigue, difficulty swallowing,
mood swings, hoarse voice, sensitivity to cold, forgetfulness, and dry/coarse skin and hair.
Lithium (Lithane, Lithromate)—Medication prescribed to treat manic (excited) phases of bipolar
disorder.
Myxedema—Hypothyroidism, characterized by
thick, puffy features, an enlarged tongue, and lack
of emotion.
Nephrosis—Any degenerative disease of the kidney
(not to be confused with nephritis, an inflammation
of the kidney due to bacteria).
Nodular goiter—An enlargement of the thyroid (goiter) caused when groups of cells collect to form
nodules.
Phenytoin (Dilantin)—Anti-convulsive medication
used to treat seizure disorders.
Propranolol (Inderal)—Medication commonly prescribed to treat high blood pressure; is a beta-adrenergic blocker and can also be used to treat irregular
heartbeat, heart attack, migraine, and tremors.
Reserpine (Serpasil)—A drug prescribed for high
blood pressure.
Salicylates—Aspirin and certain other nonsteroidal
anti-inflammatory drugs (NSAIDs).
Thiazides—A group of drugs used to increase urine
output.
Thyroid gland—A butterfly-shaped gland in front
and to the sides of the upper part of the windpipe;
influences body processes like growth, development, reproduction, and metabolism.
Thyroiditis—Inflammation of the thyroid gland.
Thyrotoxicosis—A condition resulting from high
levels of thyroid hormones in the blood.
Toxic thyroid adenoma—Self-contained concentrations of thyroid tissue that may produce excessive
amounts of thyroid hormone.

3703

Thyroid function tests

KEY TERMS

Thyroid hormones

T3RU
A high degree of resin uptake and high thyroxine
levels indicate hyperthyroidism. A low degree of resin
uptake, coupled with low thyroxine levels, is a symptom of hypothyroidism.
Thyroxine and triiodothyronine resin uptake that
are not both high or low may be a symptom of a
thyroxine-binding abnormality.
LATS
Long-acting thyroid stimulator, not usually found
in blood, is present in the blood of 80% of patients
with Graves’ disease. It is a symptom of this disease
whether or not symptoms of hyperthyroidism are
detected.
Resources
ORGANIZATIONS

American Thyroid Association, Inc. Montefiore
Medical Center, 111 E. 210th St., Bronx, NY 10467.
<http://www.thyroid.org>.
Thyroid Foundation of America, Inc. Ruth Sleeper Hall,
RSL350, 40 Parkman St., Boston, MA 02114-2698.
(800) 832-8321. <http://www.tfaeweb.org/pub/tfa >.

Maureen Haggerty

Thyroid gland removal see Thyroidectomy

lack of natural thyroxine and bringing the rate of
metabolism back to normal, artificially made thyroid
hormone improves these symptoms.
Thyroid hormones also may be used to treat goiter
(enlarged thyroid gland) and certain types of thyroid
cancer.

Description
Thyroid hormones, also called thyroid drugs, are
available only with a physician’s prescription. They are
sold in tablet form. A commonly used thyroid hormone
is levothyroxine (Synthroid, Levoxyl, Levothroid).

Recommended dosage
For adults and teenagers, the usual starting dose
of levothyroxine tablets is 0.0125 mg (12.5 micrograms) to 0.05 mg (50 micrograms) per day. The physician who prescribes the medicine may gradually
increase the dose over time.
For children, the dose depends on body weight
and must be determined by a physician.
Taking thyroid hormones exactly as directed is
very important. The physician who prescribes the
medicine will figure out exactly how much of the medicine a patient needs. Taking too much or too little can
make the thyroid gland overactive or underactive.
This medicine should be taken at the same time
every day.

Thyroid hormones
Definition
Thyroid hormones are artificially made hormones
that make up for a lack of natural hormones produced
by the thyroid gland.

Purpose
The thyroid gland, a butterfly-shaped structure in
the lower part of the neck, normally produces a hormone called thyroxine. This hormone controls the rate
of metabolism – all the physical and chemical processes that occur in cells to allow growth and maintain
body functions. When the thyroid gland does not
produce enough thyroxine, body processes slow
down. People with underactive thyroid glands feel
unusually tired and may gain weight even though
they eat less. They may also have trouble staying
warm and may have other symptoms, such as dry
skin, dry hair, and a puffy face. By making up for the
3704

Precautions
People who take thyroid hormones because their
thyroid glands do not produce enough natural hormone may need to take the medicine for the rest of
their lives. Seeing a physician regularly while taking
this medicine is important. The physician will make
sure that the medicine is working and that the dosage
is correct.
In patients with certain kinds of heart disease, this
medicine may cause chest pains and shortness of breath
during exercise. People who have this problem should
be careful not to exert themselves too much.
Anyone who is taking thyroid hormones should
be sure to tell the health care professional in charge
before having any surgical or dental procedures or
receiving emergency treatment.
This medicine is safe to take during pregnancy, but
the dosage may need to be changed. Women who are
pregnant should check with their physicians to make
sure they are taking the proper dosage.
GALE ENCYCLOPEDIA OF MEDICINE

Adrenal glands—A pair of glands located next to
the kidneys. The adrenal glands produce hormones
that control many body functions.
Hormone—A chemical that is produced in one part
of the body and then travels through the bloodstream to another part of the body where it has its
effect.
Pituitary gland—A pea-sized gland at the base of
the brain that produces many hormones that affect
growth and body functions.

Anyone who has had unusual reactions to thyroid
hormones in the past should let his or her physician
know before taking the drugs again. The physician
should also be told about any allergies to foods,
dyes, preservatives, or other substances.
Before using thyroid hormones, people with any
of these medical problems should make sure their
physicians are aware of their conditions:



increased sensitivity to heat



sweating



irritability



nervousness



sleep problems

Other side effects are possible. Anyone who has
unusual symptoms while taking thyroid hormones
should get in touch with his or her physician.

Interactions
Thyroid hormones may interact with other medicines. This may increase or decrease the effects of the
thyroid medicine and may interfere with treatment.
Anyone who takes thyroid hormones should not take
any other prescription or nonprescription (over-thecounter) medicines without the approval of his or her
physician. Among the drugs that may interact with
thyroid hormones are:


Medicine for colds, hay fever, and other allergies



Medicine for asthma and other breathing problems



Medicine for diabetes



Blood thinners



heart disease



high blood pressure



hardening of the arteries



Amphetamines



diabetes



Diet pills (appetite suppressants)



history of overactive thyroid





underactive adrenal gland

Cholesterol-lowering drugs such as cholestyramine
(Questran) and colestipol (Colestid).



underactive pituitary gland

Nancy Ross-Flanigan

Side effects
This medicine usually does not cause side effects if
the dosage is right. Certain symptoms may be signs
that the dose needs to be changed. Check with a physician if any of these symptoms occur:


headache



fever



diarrhea



vomiting



changes in appetite



weight loss



changes in menstrual period



tremors of the hands



leg cramps

GALE ENCYCLOPEDIA OF MEDICINE

Thyroid nuclear medicine scan
Definition
A thyroid nuclear medicine scan is a diagnostic
procedure to evaluate the thyroid gland, which is
located in the front of the neck and controls the
body’s metabolism. A radioactive substance that concentrates in the thyroid is taken orally or injected into
a vein (intravenously), or both. A special camera is
used to take an image of the distribution of the radioactive substance in and around the thyroid gland. This
is interpreted to evaluate thyroid function and to diagnose abnormalities.
3705

Thyroid nuclear medicine scan

KEY TERMS

Thyroid nuclear medicine scan

Purpose
A thyroid scan may be ordered by a physician
when the gland becomes abnormally large, especially
if the enlargement is greater on one side, or when hard
lumps (nodules) are felt. The scan can be helpful in
determining whether the enlargement is caused by a
diffuse increase in the total amount of thyroid tissue or
by a nodule or nodules.
When other laboratory studies show an overactive
thyroid (hyperthyroidism) or an underactive thyroid
(hypothyroidism), a radioactive iodine uptake scan is
often used to confirm the diagnosis. It is frequently
done along with a thyroid scan.

Precautions
Women who are pregnant should not have this test.

Description
This test is performed in a radiology facility,
either in an outpatient x ray center or a hospital
department. Most often, the patient is given the
radioactive substance in the form of a tasteless liquid
or capsule. It may be injected into a vein (intravenously) in some instances. Images will be taken at a
specified amount of time after this, depending on the
radioisotope used. Most often, scanning is done 24
hours later, if the radioisotope is given orally. If it is
given intravenously, the scan is performed approximately 20 minutes later.
For a thyroid scan, the patient is positioned lying
down on his or her back, with the head tilted back. The
radionuclide scanner, also called a gamma camera, is
positioned above the thyroid area as it scans. This
takes 30-60 minutes.
The uptake study may be done with the patient
sitting upright in a chair or lying down. The procedure
is otherwise the same as described for the thyroid scan.
It takes approximately 15 minutes. There is no discomfort involved with either study.
A thyroid scan may also be referred to as a thyroid
scintiscan. The name of the radioactive substance used
may be incorporated and the study called a technetium
thyroid scan or an iodine thyroid scan. The radioactive iodine uptake scan may be called by its initials, an
RAIU test, or an iodine uptake test.

Preparation
Certain medications can interfere with iodine
uptake. These include certain cough medicines, some
3706

oral contraceptives, and thyroid medications. The
patient is usually instructed to stop taking these medicines for a period of time before the test. This period
may range from several days up to three to four weeks,
depending on the amount of time the medicine takes to
clear from the body.
Other nuclear medicine scans and x ray studies
using contrast material performed within the past 60
days may affect this test. Therefore, patients should
tell their doctors if they have had either of these types
of studies before the thyroid scan is begun, to avoid
inaccurate results.
Some institutions prefer that the patient have
nothing to eat or drink after midnight on the day
before the radioactive liquid or capsule is to be
taken. A normal diet can usually be resumed two
hours after the radioisotope is taken. Dentures, jewelry, and other metallic objects must be removed
before the scanning is performed. No other physical
preparation is needed.
The patient should understand that there is
no danger of radiation exposure to themselves or
others. Only very small amounts of radioisotope
are used. The total amount of radiation absorbed is
often less than the dose received from ordinary
x rays. The scanner or camera does not emit any
radiation, but detects and records it from the
patient.

Aftercare
No isolation or special precautions are needed
after a thyroid scan. The patient should check with
his or her physician about restarting any medications
that were stopped before the scan.

Risks
There are no risks with this procedure.

Normal results
A normal scan will show a thyroid of normal
size, shape, and position. The amount of radionuclide uptake by the thyroid will be normal according
to established laboratory figures. There will be no
areas where radionuclide uptake is increased or
decreased.

Abnormal results
An area of increased radionuclide uptake may be
called a hot nodule or ‘‘hot spot.’’ This means that a
GALE ENCYCLOPEDIA OF MEDICINE

Radioisotope—A radioactive or radiation-emitting
form of an element.
Radionuclide—A substance that emits radiation as
it disintegrates.

benign growth is overactive. Despite the name, hot
nodules are unlikely to be caused by cancer.
An area of decreased radionuclide uptake may be
called a cold nodule or ‘‘cold spot.’’ This indicates that
this area of the thyroid gland is underactive. A variety
of conditions, including cysts, nonfunctioning benign
growths, localized inflammation, or cancer may produce a cold spot.
A thyroid nuclear medicine scan is rarely sufficient to establish a clear diagnosis. Frequently, the
information revealed will need to be combined with
data from other studies to determine the problem.
Resources
BOOKS

Goldsmith, Stanley J. ‘‘Endocrine System.’’ In
NuclearMedicine, edited by Donald R. Bernier, et al.
St. Louis: Mosby, 1997.

Ellen S. Weber, MSN

Thyroid sonogram see Thyroid ultrasound
Thyroid storm see Hyperthyroidism

Thyroid ultrasound
Definition
Thyroid ultrasound is an imaging technique used
for diagnosing suspected thyroid disease. It uses harmless, high-frequency sound waves to form an image.
The sound waves are reflected by thyroid tissue to
form a picture of internal structures. It is not invasive
and involves no radiation.

Purpose
The thyroid gland is an organ located in front of
the neck. It plays an important role in controlling the
GALE ENCYCLOPEDIA OF MEDICINE

body’s metabolism. Most thyroid ultrasounds are performed to evaluate a small lump (nodule) in the thyroid found during a physical examination or found by a
radionuclide study (thyroid scan). The ultrasound can
establish if the nodule is a cyst, which is an abnormal
lump that contains fluid, or a solid mass. Cysts are
almost always noncancerous (benign), although in
some cases the fluid may be taken out for additional
testing.
If there are several masses or nodules, this indicates the presence of enlargement of the thyroid
gland (goiter). If there is only one mass, it may be
cancerous and needs further evaluation. Specialized
thyroid ultrasounds, such as color Doppler flow
studies, can add valuable information. By showing
an image of the blood circulation in the gland, this
study can assess some ambiguous masses in greater
detail, to further refine diagnosis. In some cases, a
needle will be inserted to remove some tissue from
the mass for evaluation in a laboratory (needle
biopsy). Ultrasound is used during this procedure
to help the physician guide the needle to the mass
that needs to be evaluated.
Thyroid ultrasound can measure the size of the
thyroid with great precision. Ultrasound studies may
be done periodically to assess the response of the
thyroid gland to medical therapy. An enlarged gland
or a benign nodule should decrease in size when
appropriate thyroid medication is taken.
Patients who have received therapeutic radiation
to the head or neck may be monitored at regular
intervals using thyroid ultrasound. The radiation
puts these patients at higher risk for developing thyroid cancer or other abnormalities. In the early stages,
these conditions may not cause symptoms or be
apparent during a physical examination. They can,
however, be detected by ultrasound.
Certain invasive medical procedures may be performed under ultrasound guidance. This is because
ultrasound allows the physician to observe a needle
as it enters body tissue below the skin. This is useful to
direct the removal of fluid from a cyst (aspiration) or
needle biopsy. Medications to treat recurrent cysts
may be administered directly to the area using ultrasound guidance.

Precautions
Thyroid ultrasound is safe for people of all ages. It
is the preferred procedure to evaluate suspected disease in pregnant women because no radiation is
involved.
3707

Thyroid ultrasound

KEY TERMS

Thyroidectomy

Description
The study may be done in an outpatient facility or
in a hospital department. The patient lies on his or her
back. A pillow or rolled towel is placed under the
shoulders and upper back, allowing the head to tilt
back (hyperextend). A gel that enhances sound transmission is spread over the thyroid area. The technologist then gently places a transducer, an instrument
about the size of an electric shaver, against the skin.
It is moved over the thyroid area. The images from
reflected sound waves appear on a monitor screen.
There is no discomfort involved with this study. The
examination takes 15–30 minutes.

Preparation
Some facilities recommend limiting food and
drink for one hour before the study to prevent discomfort. No other preparation is needed.

Aftercare
No special restrictions or procedures are needed
after a thyroid ultrasound.

Risks
There are no risks with this procedure.

Normal results
A normal study would reveal a thyroid gland of
normal size, shape, position, and uniform texture.

Abnormal results

Definition
Thyroidectomy is a surgical procedure in which
all or part of the thyroid gland is removed. The thyroid
gland is located in the forward part of the neck (anterior) just under the skin and in front of the Adam’s
apple.

Purpose
All or part of the thyroid gland may be removed to
correct a variety of abnormalities of the gland. If the
patient has a goiter (an enlargement of the thyroid
gland, causing a swelling in the front of the neck), it
may cause difficulties with swallowing or breathing.
Hyperthyroidism (over-functioning of the thyroid
gland) produces hypermetabolism (abnormally
increased use of oxygen, nutrients, and other materials). If medication cannot adequately treat this condition, or if the patient is a child or pregnant, the thyroid
gland must be removed. Both cancerous tumors and
noncancerous tumors (frequently called nodules) can
occur and they must be removed, in addition to some
or all of the thyroid gland.

Precautions
There are definite risks associated with the procedure. Therefore, the thyroid gland should be removed
only if there is a pressing reason or medical condition
that requires it.

Description

A thyroid ultrasound may reveal cysts, solid
masses that may or may not be cancerous, or an
enlarged thyroid gland (goiter). In many cases, the
ultrasound can establish a diagnosis. Sometimes the
information revealed will need to be combined with
data from other studies to determine the problem.
Resources
PERIODICALS

Rifat, Sami F., and Mack T. Ruffin. ‘‘Management of
ThyroidNodules.’’ American Family Physician 50
(September 15, 1994): 785-791.

Ellen S. Weber, MSN

Thyroid x ray see Thyroid nuclear medicine
scan
3708

Thyroidectomy

Thyroidectomy is an operative procedure done
most commonly by a general surgeon, or occasionally
by an otolaryngologist, in the operating room of a
hospital. The operation begins when an anesthesiologist puts the patient to sleep. The anesthesiologist
injects drugs into the patient’s veins and then places
an airway tube in the windpipe to ventilate (provide air
for) the patient. The surgeon makes an incision in the
front of the neck where a tight-fitting necklace would
rest. He locates and takes care not to injure the parathyroid glands and the recurrent laryngeal nerves,
while freeing the thyroid gland from these surrounding
structures. The blood supply to the portion of the
thyroid gland that is to be removed is clamped off.
Then all or part of the gland is removed. If cancer is
present, all, or almost all, of the gland is removed. If
other diseases or a nodule is present, the surgeon may
remove only part of the gland. The total amount of
GALE ENCYCLOPEDIA OF MEDICINE

Patients generally stay in the hospital one to four
days after completion of the operation.

Preparation
Before a thyroidectomy is performed, a variety of
tests and studies are usually required to determine the
nature of the thyroid disease. Laboratory analysis of
blood determines the levels of active thyroid hormone
circulating in the body. Sonograms and computed
tomography scans (CT scans) help to determine the
size of the thyroid gland and location of abnormalities.
A thyroid nuclear medicine scan assesses the function of
the gland. A needle biopsy of an abnormality or aspiration (removal by suction) of fluid from the thyroid
gland may also be done to help determine the diagnosis.
If the diagnosis is hyperthyroidism, the patient
may be asked to take antithyroid medication or
iodides before the operation; or continued treatment
with antithyroid drugs may be the treatment of choice.
Otherwise, no other special procedure must be followed prior to the operation.

Aftercare
The incision requires little to no care after the
dressing is removed. The area may be bathed gently
with a mild soap. The sutures or the metal clips are
removed three to seven days after the operation.

Risks
As with all operations, patients who are obese,
smoke, or have poor nutrition are at greater risk for
developing complications related to the general anesthetic itself.
Hoarseness or voice loss may develop if the recurrent laryngeal nerve was injured or destroyed during
the operation. This is more apt to occur in patients
who have large goiters or cancerous tumors.
Hypoparathyroidism (under-functioning of the
parathyroid glands) can occur if the parathyroid
glands are injured or removed at the time of the
thyroidectomy.
Hypothyroidism (under-functioning of the thyroid
gland) can occur if all or nearly all of the thyroid gland
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Endocrinologist—A physician who specializes in
treating patients who have diseases of the thyroid,
parathyroid, adrenal glands, and/or the pancreas.
Hyperthyroidism—Abnormal over-functioning of
the thyroid glands. Patients are hypermetabolic,
lose weight, are nervous, have muscular weakness
and fatigue, sweat more, and have increased urination and bowel movements. This is also called
thyrotoxicosis.
Hypothyroidism—Abnormal under-functioning of
the thyroid gland. Patients are hypometabolic, gain
weight, and are sluggish.
Recurrent laryngeal nerve—A nerve which lies
very near the parathyroid glands and serves the
larynx or voice box.

is removed. This may be intentional when the diagnosis is cancer. If the patient’s thyroid levels remain high,
he may be required to take thyroid replacement for the
rest of his life.
The neck and the area surrounding the thyroid
gland have a rich supply of blood vessels. Bleeding in
the area of the operation may occur and be difficult to
control or stop. Rarely is a blood transfusion required,
although a hematoma (collection of blood) may
develop. If this occurs, it may be life-threatening. As
the hematoma enlarges, it may obstruct the airway
and cause the patient to stop breathing. If a hematoma
does develop in the neck, it may require drainage to
clear the airway.
Wound infections can occur. If they do, the incision is drained, and there are usually no serious
consequences.

Normal results
Most patients are discharged from the hospital
one to four days after the procedure. Most resume
their normal activities two weeks after the operation.
Patients who have cancer may require subsequent
treatment by an oncologist or a endocrinologist.
Resources
OTHER

‘‘Thyroid Gland Removal.’’ ThriveOnline. <http://
thriveonline.oxygen.com>.

Mary Jeanne Krob, MD, FACS
3709

Thyroidectomy

thyroid gland removed depends upon the thyroid disease being treated. A drain (a soft plastic tube that
drains fluid out of the area) may be placed before the
incision is closed. The incision is closed either with
sutures (stitches) or metal clips. A dressing is placed
over the incision and the drain, if one is used.

Thyroiditis

Thyroiditis
Definition
Thyroiditis is inflammation of the thyroid gland, a
butterfly-shaped organ next to the windpipe.

Description
The thyroid is the largest gland in the neck. It
produces, secretes, and stores thyroxine (T4), a hormone that influences the metabolism of just about
every body process.
When the thyroid gland is functioning properly,
hormone release is carefully regulated. When bacteria
or viruses invade and inflame the gland, T4 surges
into the bloodstream and raises hormone levels that
then discourage the gland from creating more T4.
Eventually the hormone stores are exhausted, the thyroid loses its ability to manufacture T4, and an underactive thyroid (hypothyroidism) results.
The major cause of hypothyroidism, thyroiditis
affects about 12 million people in the United States.
This condition is more common in women than in men
and usually develops between ages 30–50.

infection, such as mumps or an upper respiratory illness. Pain radiates throughout the neck and patients
feel ill and feverish. It may take as long as several
months for normal thyroid function to resume.
Subacute thyroiditis is also called:


DeQuervain’s thyroiditis



giant cell thyroiditis



granulomatous thyroiditis



subacute granulomatous thyroiditis
Silent thyroiditis

The least common of the three major types, silent
thyroiditis is characterized by rigidity and slight enlargement of the thyroid gland. Postpartum thyroiditis, a
form of silent thyroiditis, develops in 5–9% of all
women who have recently given birth. Postpartum
thyroiditis develops within a year of the baby’s birth
and disappears within six months.
Acute thyroiditis
Caused by acute infection, this rare disease is a
medical emergency. A patient who has acute thyroiditis has a high fever and feels very ill. The neck is red,
hot, and very tender.

Hashimoto’s disease

Causes and symptoms

The most common type of thyroiditis is
Hashimoto’s disease, a painless disorder also known as:

Hashimoto’s disease



autoimmune thyroiditis



chronic lymphocytic thyroiditis



lymphadenoid goiter

Hashimoto’s disease develops when the immune
system attacks the thyroid gland. It may be related to
such hormone-related (endocrine system) disorders as:



Struma lymphomatosa



Addison’s disease. This condition, caused by malfunction of the adrenal gland, is characterized by
weakness, loss of weight and appetite, and increased
sensitivity to cold.



Diabetes mellitus. This metabolic disorder is caused
by a lack of insulin production or by the body’s
inability to process insulin.



Graves’ disease. This disease is the most common
form of hyperthyroidism.



Vitiligo. This is a noncancerous skin disease characterized by unpigmented patches of skin.

Hashimoto’s disease can develop at any age, but is
most common in middle-aged women. This immune
system disorder runs in families, and affects about 5%
of adults in the United States.
Hashimoto’s disease slowly destroys thyroid tissue and robs the gland of its ability to change iodine
into T4. The condition progresses so gradually that
many people who have it do not realize anything is
wrong until the enlarged gland forms a goiter, a swelling seen and felt in the front of the neck. This may not
happen until weeks or even years after an individual
develops Hashimoto’s.
Subacute thyroiditis
Much less common than Hashimoto’s disease,
subacute thyroiditis is a painful inflammation that
develops suddenly in a patient who has had a viral
3710

Being female and having a family history of
Hashimoto’s thyroiditis increases the likelihood of
developing the disease. Its symptoms include:


constipation



fatigue



goiter or enlarged neck
GALE ENCYCLOPEDIA OF MEDICINE

inability to tolerate cold temperatures

Treatment



weight gain, some patients’ faces swell and their
joints stiffen.

Medical therapy for thyroiditis includes:

Subacute thyroiditis
Characterized by painful gland enlargement that
is sometimes mistaken for a sore throat that may last
for months, subacute thyroiditis often follows:


influenza



mumps



upper respiratory infections



viruses that produce cold symptoms and inflammation of the membrane that protects the brain (meningitis), inflammation of the sac that surrounds the
heart (pericarditis), inflammation of the heart muscle
(myocarditis), and other diseases

People who have subacute thyroiditis feel feverish,
weak, and tired. The thyroid is sore to the touch. They
may be nervous, sweat, and have trouble tolerating
heat or swallowing. Symptoms of subacute thyroiditis
also include:


rapid heartbeat



tremors



weight loss.
Silent thyroiditis

The cause of silent thyroiditis is uncertain, but the
condition is believed to be an immune-system disorder
triggered by childbirth. Although silent thyroiditis is
painless, the condition’s other symptoms are similar to
those of subacute thyroiditis. The thyroid gland
enlarges only slightly, and the eyes do not bulge.

Diagnosis
Family physicians and endocrinologists usually
base a diagnosis of thyroiditis on:




antibiotics to fight infection



high doses of aspirin to relieve inflammation



hormones to suppress or replace thyroid function



pain medications

Cortisone drugs are sometimes prescribed to
reduce persistent inflammation. In rare instances, surgery can be used to drain infection or relieve pressure
near the thyroid gland.
Hashimoto’s disease
The goal of treatment for Hashimoto’s disease is
to prevent the thyroid gland from getting larger.
Regular monitoring may be the only treatment indicated for patients whose gland is only slightly
enlarged, and who show no signs of hormone deficiency. Levothyroxine (Synthroid) may be prescribed
to correct hormone deficiency in a patient who has a
large goiter.
Subacute thyroiditis
The goal of treatment for subacute thyroiditis is to
relieve pain, reduce inflammation, and regulate
hyperthyroidism. Bed rest and beta blockers (propranolol, naldolol) may be necessary until thyroid activity
is controlled, and the patient may have to take:


anti-inflammatory medication for several weeks



high doses of aspirin



other analgesics

If subacute thyroiditis continues for a long time,
cortisone and thyroid hormone medication may
be prescribed to relieve inflammation and allow
the gland to rest. Glucocorticoids (prednisone) are prescribed for symptoms that do not respond to other
treatment. The original problem often becomes more
pronounced after these medications are discontinued.

blood levels of thyroid hormones, thyroid-stimulating
hormone, and anti-thyroid antibodies



personal and family medical history



the appearance of a patient’s thyroid gland

Thyroid antibodies present in 95% of patients
with Hashimoto’s thyroiditis make it possible to diagnose this disease without surgery or biopsy. A blood
test that measures sedimentation rate, an indication of
the extent of inflammation, is a useful tool for diagnosing subacute thyroiditis.
GALE ENCYCLOPEDIA OF MEDICINE

Thyroiditis



Silent thyroiditis
Most patients who have silent thyroiditis don’t
need any treatment, but:


bed rest and beta blockers are occasionally needed to
regulate rapid heart beat



inderal (propanolol) may be prescribed for brief periods of hyperthyroidism



steroids may be prescribed for severe episodes of
acute inflammation
3711

Tilt table test

KEY TERMS
Addison’s disease—A disease that results from a
deficiency in adrenocortical hormones.
Diabetes mellitus—A disorder of the pancreas. This
chronic disorder of carbohydrate metabolism
results in hyperglycemia and glycosuria.
Goiter—An abnormal enlargement of the thryroid
gland.
Graves’ disease—Also called hyperthyroidism, this
disease results from overactivity of the thyroid
gland.
Subacute—An abnormal condition present in a
person who appears to be clinically well.
Vitiligo—A benign skin disease that results in irregular patches of skin that are totally lacking in color.

12 months. Because silent thyroiditis recurs in 10%
of patients within three years and may progress to
hypothyroidism, medical monitoring should continue
for three years after recovery appears complete.

Prevention
Flu shots or immunizations for measles, mumps,
and rubella may help prevent conditions associated
with subacute thyroiditis. There is no known way to
prevent other forms of thyroiditis.
Resources
ORGANIZATIONS

Thyroid Foundation of America. 350 Ruth Sleeper Hall,
Parkman St., Boston, MA 02114. (800) 232-8321.
<http://www.clark.net/pub/tfa>.
Thyroid Society for Education and Research. 7515 South
Main St., Suite 545, Houston, TX 77030. (800) 8497643. <http:the-thyroid-society.org/thyroid.html>.

Maureen Haggerty

Acute thyroiditis
Acute thyroiditis requires emergency treatment
with antibiotics and surgery.

Prognosis
Thyroiditis usually responds to treatment, and
some patients recover normal thyroid function without treatment. Because permanent loss of thyroid
function is a possibility and life-long thyroid replacement therapy may be necessary, regular medical monitoring should continue even after the patient has
apparently recovered.

Thyrotoxicosis see Hyperthyroidism
Thyroxine-binding globulin test see Thyroid
function tests
Thyroxine test see Thyroid function tests
TIA see Transient ischemic attack
Tic douloureux see Trigeminal neuralgia
Tick fever see Relapsing fever

Hashimoto’s disease
Some cases of Hashimoto’s disease remain stable
for years. Others slowly progress to hypothyroidism,
which is treated with thyroid hormone replacement
therapy.
Subacute thyroiditis
Most patients with subacute thyroiditis recover
fully after no more than a few months. This condition
occasionally recurs, but severe or long-term complications are rare.
Silent thyroiditis
Four of every five patients with silent thyroiditis
recover completely within three months. The thyroid
status of these patients should be evaluated within
3712

Tilt table test
Definition
The tilt table test is a test in which a patient is
positioned in a supine position and brought to a predetermined angle or angles from the horizontal position. Such positioning helps to determine the cause of
any decrease in oxygen to the brain. Different types of
drugs may also used in the testing process.

Purpose
The purpose of the tilt table test is to help determine appropriate therapy for individuals with fainting
(syncope) and presyncope of unexplained origin.
GALE ENCYCLOPEDIA OF MEDICINE

Precautions are few with the tilt table test.
However, when any drug is used with this test, the
appropriate precautions for that particular drug
should be observed. For example, when isoproterenol
or similiar drugs are used during the tilt table test, the
taking of non-prescription drugs for asthma, cough,
cold, or allergy; appetite suppressants; sleeping pills;
or drugs containing caffeine should be made known to
the physician prior to the test. Likewise, the physician
should be informed of any allergies to any sympathomimetic drugs, including several of the diet pills on the
market. The physician should be told of any serious
heart-rhythm disorders.

Description
Syncope is described as a pathological brief loss of
consciousness caused by a temporary deficiency of
oxygen in the brain. Previous studies have shown the
effectiveness of tilt table testing in establishing the
diagnosis of neurocardiogenic syncope, and in dictating therapy in patients with syncope of unknown origin. Despite its usefulness, small numbers of patients
and brief followup reports have limited the majority of
studies. Sensitivity-enhancing techniques, such as the
administration of isoproterenol, are applied in specific
cases to children and young adults to compensate for
the otherwise low sensitivity (20-30%) observed in
that population.

KEY TERMS
Sympathomimetic—Denoting a drug that mimics
the effects of stimulation of organs and structures by
the sympathetic nervous system. The sympathetic
nervous system pertains to the part of the nervous
system originating in the thoracic and lumbar
regions of the spinal cord. In general, it inhibits or
opposes the physiological effects of another aspect
of the nervous system, as in tending to reduce
digestive secretions, speed up the heart, and contract the blood vessels.
Syncope—A loss of consciousness over a short period of time, caused by a temporary lack of oxygen
in the brain.
Vertigo—The sensation of dizziness.

When ready, the individual transfers from the sitting
position to standing. After additional observation
and taking of vital signs, the individual is allowed to
go home.

Risks
Risks of the tilt table test are low, but do include
significant changes in blood pressure while in the
supine position, and any adverse reactions to any
drugs administered during the tilt table test.

Preparation
In order for a patient to make informed decisions
about any diagnostic test or procedure, there are
important questions that need to be asked prior to
the procedure. The information gained will be helpful
for that patient in determining benefits, risks, and cost
of the procedure, and alternatives. The patient should
understand the purpose of the tilt table test, and the
diagnosis that the physician is trying to confirm or rule
out. If the tilt table test is positive, the patient should
ask questions about the frequency of false-positive
results for that particulare tilt table procedure, and
should inquire about the next step in treatment.

Normal results
Normal results of the tilt table test should help the
physician in assessing what may or may not be the
cause of the syncope.

Abnormal results
Abnormal results include any pathologic reactions to the position changes or sensitivity enhancing
techniques, such as the administration of isoproterenol or other related drugs.
Resources

Aftercare
After the procedure, the patient is asked to transfer from the supine position to a sitting position, and
is observed for a short period of time. During this
time and after several minutes in the sitting position,
any symptoms of dizziness and vertigo are noted.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Medical Association. 515 N. State St., Chicago,
IL 60612. (312) 464-5000. <http://
www.amaassn.org>.

Jeffrey P. Larson, RPT
3713

Tilt table test

Precautions

Tinnitus

Tinea cruris see Ringworm
Tinea pedis see Athlete’s foot
Tingling see Numbness and tingling

an otoscope to examine the ears for wax, infection, or
structural changes. He or she will also use a stethoscope to listen to the blood vessels in the neck.
Additional tests may include the following:
Tuning fork tests

Tinnitus
Definition
Tinnitus is hearing ringing, buzzing, or other
sounds without an external cause. Patients may
experience tinnitus in one or both ears or in the head.

Description
Tinnitus affects as many as 40 million adults in
the United States. It is defined as either objective or
subjective. In objective tinnitus, the doctor can hear
the sounds, as well as the patient. Objective tinnitus
is typically caused by tumors, turbulent blood flow
through malformed vessels, or by rhythmic muscular spasms. Most cases of tinnitus are subjective,
which means that only the patient can hear the
sounds.

The Rinne and Weber tests are commonly used to
evaluate the type and severity of hearing loss. In the
Weber test, the doctor holds a tuning fork against the
patient’s forehead or front teeth. If the hearing loss is
sensorineural, the sound radiates to the ear with better
hearing; if the hearing loss is conductive, the sound
will be louder in the damaged ear. In the Rinne test,
the tuning fork is placed alternately on the mastoid
bone (behind the ear) and in front of the ear. In conductive hearing loss, bone conduction (BC) is greater
than air conduction (AC). In sensorineural hearing
loss, AC is greater than BC.
Diagnostic imaging
Magnetic resonance angiography or venography
(MRA and MRV) can be used to evaluate malformations of the blood vessels. Computed tomography scans
(CT scans) or magnetic resonance imaging scans
(MRIs) can be used to locate tumors or abnormalities
of the brain stem.

Causes and symptoms
Subjective tinnitus is frequently associated with
hearing loss. About 90% of patients have sensorineural hearing loss; 5% suffer from conductive hearing
loss; 5% have normal hearing. The causes of subjective tinnitus include:


impacted ear wax



ear infections



hardening of the structures of the inner ear



hearing loss related to age or excessive noise



ototoxic medications, including aspirin, quinine,
some diuretics, heavy metals, alcohol, and certain
antibiotics



meniere’s syndrome



head trauma



systemic diseases, including syphilis, hypertension,
anemia, or hypothyroidism



tumors of the ear

Blood tests
The doctor may order a complete blood count
(CBC) with specific antibody tests to rule out syphilis
or immune system disorders.

Treatment
Some cases of tinnitus can be treated by
removal of the underlying cause. These include
surgical treatment of impacted ear wax, tumors,
head injuries, or malformed blood vessels; discontinuance of ototoxic medications; and antibiotic
treatment of infections.
Subjective tinnitus, especially that associated with
age-related hearing loss, can be treated with hearing
aids, noise generators or other masking devices, biofeedback, antidepressant medications, or lifestyle
modifications (elimination of smoking, coffee, and
aspirin).

Alternative treatment
Diagnosis
Diagnosis of tinnitus includes a physical examination of the patient’s head and neck. The doctor will use
3714

A variety of alternative therapies may be helpful
in the treatment of tinnitus. Dietary adjustments,
including the elimination of coffee and other
GALE ENCYCLOPEDIA OF MEDICINE

Conductive hearing loss—Hearing loss caused by
loss of function in the external or middle ear.
Meniere’s syndrome—A disease of the inner ear,
marked by recurrent episodes of loss of balance
(vertigo) and roaring in the ears lasting several
hours. Its cause is unknown.
Ototoxic—Damaging to the nerves controlling the
senses of hearing and balance.
Sensorineural hearing loss—Hearing loss caused
by damage to the nerves or parts of the inner ear
governing the sense of hearing.

stimulants, may be useful, since stimulants can make
tinnitus worse. In addition, reducing the amount of
fat and cholesterol in the diet can help improve blood
circulation to the ears. Nutritional supplementation
with vitamin C, vitamin E, B vitamins, calcium, magnesium, potassium, and essential fatty acids is also
recommended. Gingko (Gingko biloba) is often suggested, since it is believed to enhance circulation to
the brain. Acupuncture treatments may help decrease
the level of tinnitus sounds the patient hears, and
constitutional homeopathic treatment may also be
effective.

Prognosis
The prognosis depends on the cause of the tinnitus
and the patient’s emotional response. Most patients
with subjective tinnitus do not find it seriously disturbing, but about 5% have strong negative feelings. These
patients are frequently helped by instruction in relaxation techniques.
Resources

Tissue typing
Definition
Tissue typing is a group of procedures that determines the type of histocompatibility antigens on a
person’s cells or tissues. This procedure is typically
used prior to transplantation of tissues or organs.

Purpose
Tissue typing is done prior to transplantation to
ensure as close a match as possible between the donor
and the recipient. If the histocompatibility antigens do
not match well, there is a much greater chance that the
recipient will reject the donated tissue.
Histocompatibility antigens are molecules on the
surface of all cells in the body. The specific types of
histocompatibility antigens present on a person’s cells
determine their identity and distinguish each person.
They are a ‘‘fingerprint.’’
Each person has a unique set of histocompatibility
antigens. If the antigens on tissue or organs from a donor
do not match that of the recipient, a rejection response
can occur. The recipient’s immune system will detect the
difference between the two sets of antigen and start a
rejection response to kill the donated tissue. Except in the
case of identical twins, no two people are identical in
terms of their histocompatibility antigen types. However,
the closer two tissues come to matching, the more likely
the recipient will accept the donated tissue or organ.
Human Lymphocyte Antigens (HLA) is the name
given to the most commonly used histocompatibility
antigens. The antigens can be grouped into two
classes: class I antigens are found on almost all cells,
and class II antigens are normally found only on B
lymphocytes, macrophages, monocytes, dendritic
cells, and endothelial cells.

Description

BOOKS

Jackler, Robert K., and Michael J. Kaplan. ‘‘Ear, Nose, &
Throat.’’ In Current Medical Diagnosis and Treatment,
1998, edited by StephenMcPhee, et al., 37th ed.
Stamford: Appleton & Lange, 1997.

Rebecca J. Frey, PhD

Tissue compatibility see Tissue typing
Tissue plasminogen activator see
Thrombolytic therapy
GALE ENCYCLOPEDIA OF MEDICINE

Generally, typing is performed on blood cells
because they are an easy sample to obtain. Blood is
withdrawn from a vein in the forearm, and the cells
are separated. There are a number of different techniques used to identify the antigens on the cells. Typically,
specific antibodies react with the cells. Each antibody
preparation is specific for one histocompatibility antigen. If the antigen is present, the antibody will bind to
it. Laboratory instruments are used to detect antibody
binding to the cells. Class II antigens are determined by
the mixed lymphocyte reaction (MLR) or by a polymerase chain reaction (PCR). In the mixed lymphocyte
3715

Tissue typing

KEY TERMS

Tonsillectomy and adenoidectomy

Tonsil removal see Tonsillectomy and
adenoidectomy

KEY TERMS
Antibody—A molecule produced by the body that
is part of the immune response to attack antigens.
Antigen—A molecule that causes the body to produce an immunological response to attack the
antigen.
Cornea—The transparent outer layer of the eye. It
covers the iris and lens.
Lymphocyte—A class of white blood cells that are
responsible for creating the immune response to
antigens.

reaction, lymphocyte replication occurs if there is a
mismatch, and is detected by a specific assay. The
PCR test is a new DNA-based test that can detect the
presence or absence of antigens by determining whether
cells have the genes for the antigens.
One type of transplant does not require tissue
typing. In the case of corneal transplants, tissue typing
is not needed because cornea do not have their own
blood supply. This greatly reduces the chance that
immune cells will come in contact with the cornea
and recognize it as foreign. For this reason, corneas
can be transplant from any person, and there is little
chance of rejection.

Tonsillectomy and
adenoidectomy
Definition
Tonsillectomy and adenoidectomy (T & A) are
surgical procedures to remove the tonsils from the
back of the mouth or adenoids from the back of the
nasal cavity – both are are part of the lymphatic system, which is responsible for fighting infection. These
operations are often performed together and are
usually done on children. T & As are the most common childhood operations.

Purpose
Tonsillectomy
Tonsils are removed (with or without the adenoids) when the child has any of the following
conditions:


obstruction



sleep apnea. This is a condition in which the child
snores loudly and stops breathing temporarily at
intervals during sleep



inability to swallow properly because of enlarged
tonsils



‘‘hot potato’’ voice (breathy voice) and other speech
abnormalities due to enlarged tonsils



recurrent or persistent abscesses or throat infections

Normal results
Because each person has their own histocompatibility antigen ‘‘fingerprint,’’ there is no true normal
result. Each fingerprint is unique.
Resources
BOOKS

Berkow, Robert, editor. Merck Manual of Medical
Information. Whitehouse Station, NJ: Merck Research
Laboratories, 1997.

John T. Lohr, PhD

Doctors do not agree completely on the number of
sore throats that make a tonsillectomy necessary.
Most would agree that four cases of strep throat in
any one year; six or more episodes of tonsillitis in one
year; or five or more episodes of tonsillitis per year for
two years indicate that the tonsils should be removed.

TMJ see Temporomandibular joint disorders

Adenoidectomy

Tobramycin see Aminoglycosides;
Antibiotics, ophthalmic

Adenoids are removed (with or without the tonsils) when the child has any of the following
conditions:

Tocopherol deficiency see Vitamin E
deficiency



alteration of facial growth because of enlarged
adenoids

Toenail removal see Nail removal



upper airway obstruction

3716

GALE ENCYCLOPEDIA OF MEDICINE

Tonsillectomy and adenoidectomy

Tonsils

Scalpel

Uvula

Tongue

Toothed forceps

Tongue depressor

Tonsillectomy and adenoidectomy are surgical procedures performed to remove the tonsils or adenoids. The tonsils are
removed in cases where they are a source of recurrent infection or have developed an abscess. Both operations are typically
performed on children. The illustration above shows a tonsillectomy in progress. (Illustration by Electronic Illustrators Group.)



development of
malocclusion)

an

irregular



difficult speech or swallowing

bite

(dental

Precautions
T & As are not performed as frequently today as
they were in the past. One reason for a more conservative approach is that there is always some risk
involved when a patient is put under general
anesthesia.
In some cases, a T & A may need to be modified or
postponed:


children with cleft palates should not have the adenoids removed



bleeding disorders; these must be brought under control before surgery



acute tonsillitis; surgery should be postponed–usually
for three to four weeks–until the infection is gone

Description
Tonsillectomies are hospital procedures. In
adults, they may be performed under local anesthesia.
GALE ENCYCLOPEDIA OF MEDICINE

Children are usually placed under general anesthesia.
The doctor depresses the tongue in order to see the
throat and removes the tonsils with a scooplike instrument. The adenoids are usually removed through the
nose.

Aftercare
Patients are turned on the side after the operation
to prevent the possibility of blood being drawn into
the lungs. The patient’s vital signs are checked. After
the patient is fully awake, he or she can drink water
and other nonirritating liquids.
Adult patients are usually warned to expect
some bleeding after the operation and a very sore
throat. Antibiotics are given to prevent infection.
Medications to relieve pain may also be given. For
at least the first 24 hours, the patient is fed soft or
pureed foods and fluids. If the adenoids alone were
removed, the patient may be allowed solid food the
day after surgery.
Patients are usually sent home the next day, with
instructions to call the doctor if there is bleeding, an
earache, or a fever that lasts longer than three days.
3717

Tonsillitis

Description

KEY TERMS
Abscess—A localized area of tissue destruction and
pus formation.
Adenoids—Masses of lymphoid tissue that are
found in the upper throat.
Sleep apnea—A condition marked by loud snoring
during sleep and periodic episodes of suspended
breathing.
Tonsils—Oval masses of lymphoid tissue on each
side of the throat.

They are told to expect a white scab to form in the
throat between five and 10 days after surgery.

Risks
About one in every fifteen thousand tonsillectomies
ends in death, either from the anesthesia or from bleeding to death five to seven days after the operation. There
is also a chance that children with previously normal
speech will develop a nasal-sounding voice. In addition,
children younger than five years may be badly emotionally upset by the hospital experience.

Normal results
Normal results include the correction of the condition for which the surgery was performed.
Resources
BOOKS

Berman, Stephen, and Ken Chan. ‘‘Ear, Nose, & Throat.’’ In
Current Pediatric Diagnosis & Treatment, edited by
William W. Hay, Jr., et al. Stamford: Appleton &
Lange, 1997.

Rebecca J. Frey, PhD

Tonsillitis
Definition
Tonsillitis is an infection and swelling of the tonsils, which are oval-shaped masses of lymph gland
tissue located on both sides of the back of the throat.
3718

The tonsils normally help to prevent infections.
They act like filters to trap bacteria and viruses entering the body through the mouth and sinuses. The
tonsils also stimulate the immune system to produce
antibodies to help fight off infections. Anyone of any
age can have tonsillitis; however, it is most common in
children between the ages of five and 10 years.

Causes and symptoms
Tonsillitis is caused by viruses or bacteria that
cause the tonsils to swell and become inflamed. A
mild or severe sore throat is one of the first symptoms
of tonsillitis. Symptoms can also include fever, chills,
tiredness, muscle aches, earache, pain or discomfort
when swallowing, and swollen glands in the neck. Very
young children may be fussy and stop eating. When a
doctor or nurse looks into the mouth with a flashlight,
the tonsils may appear swollen and red. Sometimes,
the tonsils will have white or yellow spots or flecks or a
thin coating. Symptoms usually last four to six days.

Diagnosis
The diagnosis of tonsillitis is made from the visible
symptoms and a physical examination of the patient.
The doctor will examine the eyes, ears, nose, and throat,
looking at the tonsils for signs of swelling, redness, or a
discharge. A careful examination of the throat is necessary to rule out diphtheria and other conditions that
may cause a sore throat. Since most sore throats in
children are caused by viruses rather than bacteria, the
doctor may take a throat culture in order to test for the
presence of streptococcal bacteria. A throat culture is
performed by wiping a cotton swab across the tonsils
and back of the throat, and sending the swab to a
laboratory for culturing. Streptococcus pyogenes, the
bacterium that causes strep throat, is the most common
disease agent responsible for tonsillitis. Depending on
what type of test is used for strep, the doctor may be
able to determine within a few minutes if S. pyogenes is
present. The quick tests for strep are not as reliable as a
laboratory culture, which can take 24–48 hours. If the
results of a quick test are positive, however, the doctor
can prescribe antibiotics right away. If the quick test
results are negative, the doctor can do a throat culture
to verify the results and wait for the laboratory report
before prescribing antibiotics. A blood test may also be
done to rule out a more serious infection or condition,
and to check the white blood cell count to see if the body
is responding to the infection. In some cases, the doctor
GALE ENCYCLOPEDIA OF MEDICINE

Tonsillitis

Palatine tonsil
Pharyngeal
tonsil

Lingual tonsil

Nasal cavity

Tongue

Palatine tonsil
Lingual tonsil

The palatine, lingual, and pharyngeal tonsils. (Illustration by Hans & Cassady, Inc.)

An examination of this patient’s mouth reveals acute tonsillitis.
(Custom Medical Stock Photo. Reproduced by permission.)

drinking extra fluids, gargling with warm salt water,
and taking pain relievers–usually NSAIDs–to reduce
fever. Frozen juice bars and cold fruit drinks can bring
some temporary relief of sore throat pain; drinking
warm tea or broth can be soothing. If the throat
culture shows that S. pyogenes is present, penicillin
or other antibiotics will be prescribed. An injection
of benzathine or procaine penicillin may be most effective in treating the infection, but it is also painful. If an
oral antibiotic is prescribed, it must be taken for the
full course of treatment, usually 10-14 days. If the
patient has several episodes of severe tonsillitis, the
doctor may recommend a tonsillectomy, which is the
surgical removal of the tonsils.

Alternative treatment
may order blood tests for mononucleosis, since about a
third of patients with mononucleosis develop streptococcal infections of the tonsils.

Treatment
Treatment of tonsillitis usually involves keeping
the patient comfortable while the illness runs its
course. This supportive care includes bed rest,
GALE ENCYCLOPEDIA OF MEDICINE

Strengthening the immune system is important
whether tonsillitis is caused by bacteria or viruses.
Naturopaths often recommend dietary supplements of
vitamin C, bioflavonoids, and beta-carotenes–found
naturally in fruits and vegetables–to ease inflammation
and fight infection. A variety of herbal remedies
also may be helpful in treating tonsillitis. Calendula
(Calendula officinalis) and cleavers (Galium aparine) target the lymphatic system, while echinacea (Echinacea
3719

Tooth decay

KEY TERMS
Streptococcus pyogenes—A common bacterium
that causes strep throat and can also cause
tonsillitis.
Tonsillectomy—A surgical procedure to remove
the tonsils if the patient has recurrent sore throats
or throat infections, or if the tonsils have become so
swollen that the patient has trouble breathing or
swallowing.
Tonsils—Oval-shaped masses of glandular tissue
located on both sides at the back of the throat.
Tonsils act like filters to trap bacteria and viruses.

spp.) and astragalus (Astragalus membranaceus) stimulate the immune system. Goldenseal (Hydrastis canadensis), myrrh (Commiphora molmol), and bitter orange act
as antibacterials. Lomatium dissectum and Ligusticum
porteri have an antiviral action. Some of the homeopathic medicines that may be used to treat symptoms
of tonsillitis include Belladonna, Phytolacca, Mercurius,
Lycopodium, Lachesis, Hepar sulphuris, Arsenicum, or
Rhus toxicodendron. As with any condition, the treatment and dosage should be appropriate for the particular symptoms and age of the patient.

Prognosis
Tonsillitis usually resolves within a few days with
rest and supportive care. Treating the symptoms of
sore throat and fever will make the patient more comfortable. If fever persists for more than 48 hours,
however, or is higher than 1028F, the patient should
be seen by a doctor. If antibiotics are prescribed to
treat an infection, they should be taken as directed for
the complete course of treatment, even if the patient
starts to feel better in a few days. Prolonged symptoms
may indicate that the patient has other upper respiratory infections, most commonly in the ears or sinuses.
An abscess behind the tonsil (a peritonsillar abscess)
may also occur. In rare cases, a persistent sore throat
may point to more serious conditions, such as rheumatic fever or pneumonia.

transmission can be lowered by avoiding exposure to
anyone who already has tonsillitis or a sore throat.
Drinking glasses and eating utensils should not be
shared and should be washed in hot, soapy water
before reuse. Old toothbrushes should be replaced to
prevent reinfection. People who are caring for someone with tonsillitis should wash their hands frequently,
to prevent spreading the infection to others.
Resources
OTHER

‘‘Tonsillitis.’’ Kids Health Page. <http://KidsHealth.org/
parent/common/tonsillitis.html>.

Altha Roberts Edgren

Tooth decay
Definition
Tooth decay, which is also called dental cavities or
dental caries, is the destruction of the outer surface
(enamel) of a tooth. Decay results from the action of
bacteria that live in plaque, which is a sticky, whitish
film formed by a protein in saliva (mucin) and sugary
substances in the mouth. The plaque bacteria sticking
to tooth enamel use the sugar and starch from food
particles in the mouth to produce acid.

Description
Tooth decay is a common health problem, second
in prevalence only to the common cold. It has been
estimated that 90% of people in the United States
have at least one cavity, and that 75% of people had
their first cavity by the age of five. Although anyone can
have a problem with tooth decay, children and senior
citizens are the two groups at highest risk. Other highrisk groups include people who eat a lot of starchy and
sugary foods; people living in areas without a fluoridated water supply; and people who already have
numerous dental restorations (fillings and crowns).
Baby bottle tooth decay

Prevention
The bacteria and viruses that cause tonsillitis are
easily spread from person to person. It is not unusual
for an entire family or several students in the same
classroom to come down with similar symptoms, especially if S. pyogenes is the cause. The risk of
3720

Baby bottle tooth decay is a dental problem that
frequently develops in infants that are put to bed with
a bottle containing a sweet liquid. Baby bottle tooth
decay is also called nursing-bottle caries and bottlemouth syndrome. Bottles containing such liquids as
milk, formula, fruit juices, sweetened drink mixes, and
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Tooth decay requires the simultaneous presence
of three factors: plaque bacteria, sugar, and a vulnerable tooth surface. Although several microorganisms
found in the mouth can cause tooth decay, the primary
disease agent appears to be Streptococcus mutans. The
sugars used by the bacteria are simple sugars such as
glucose, sucrose, and lactose. They are converted primarily into lactic acid. When this acid builds up on an
unprotected tooth surface, it dissolves the minerals in
the enamel, creating holes and weak spots (cavities).
As the decay spreads inward into the middle layer (the
dentin), the tooth becomes more sensitive to temperature and touch. When the decay reaches the center of
the tooth (the pulp), the resulting inflammation (pulpitis) produces a toothache.

Diagnosis
Tooth decay develops at varying rates. It may be
found during a routine six-month dental checkup
before the patient is even aware of a problem. In
other cases, the patient may experience common
early symptoms, such as sensitivity to hot and cold
liquids or localized discomfort after eating very sweet
foods. The dentist or dental hygienist may suspect
tooth decay if a dark spot or a pit is seen during a
visual examination. Front teeth may be inspected for
decay by shining a light from behind the tooth. This
method is called transillumination. Areas of decay,
especially between the teeth, will appear as noticeable
shadows when teeth are transilluminated. X rays may
be taken to confirm the presence and extent of the
decay. The dentist then makes the final clinical diagnosis by probing the enamel with a sharp instrument.
Tooth decay in pits and fissures may be differentiated from dark shadows in the crevices of the chewing surfaces by a dye that selectively stains parts of the
tooth that have lost mineral content. A dentist can also
use this dye to tell whether all tooth decay has been
removed from a cavity before placing a filling.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis in children
Damage caused by baby bottle tooth decay is
often not diagnosed until the child has a severe problem, because parents seldom bring infants and toddlers in for dental check-ups. Dentists want to initially
examine primary teeth between 12 and 24 months.
Children still drinking from a bottle anytime after
their first birthday are likely to have tooth decay.

Treatment
To treat most cases of tooth decay in adults, the
dentist removes all decayed tooth structure, shapes the
sides of the cavity, and fills the cavity with an appropriate material, such as silver amalgam or composite
resin. The filling is put in to restore and protect the
tooth. If decay has attacked the pulp, the dentist or a
specialist called an endodontist may perform root
canal treatment and cover the tooth with a crown.
In cases of baby bottle tooth decay, the dentist
must assess the extent of the damage before deciding
on the treatment method. If the problem is caught
early, the teeth involved can be treated with fluoride,
followed by changes in the infant’s feeding habits and
better oral hygiene. Primary teeth with obvious decay
in the enamel that has not yet progressed to the pulp
need to be protected with stainless steel crowns.
Fillings are not usually an option in small children
because of the small size of their teeth and the concern
of recurrent decay. When the decay has advanced to
the pulp, pulling the tooth is often the treatment of
choice. Unfortunately, loss of primary teeth at this age
may hinder the young child’s ability to eat and speak.
It may also have bad effects on the alignment and
spacing of the permanent teeth when they come in.

Prognosis
With timely diagnosis and treatment, the progression of tooth decay can be stopped without extended
pain. If the pulp of the tooth is infected, the infection
may be treated with antibiotics prior to root canal
treatment or extraction. The longer decay goes
untreated, however, the more destructive it becomes
and the longer and more intensive the necessary treatment will be. In addition, a patient with two or more
areas of tooth decay is at increased risk of developing
additional cavities in the future.

Prevention
It is easier and less expensive to prevent tooth
decay than to treat it. The four major prevention
3721

Tooth decay

sugar water continuously bathe an infant’s mouth
with sugar during naps or at night. The bacteria in
the mouth use this sugar to produce acid that destroys
the child’s teeth. The upper front teeth are typically the
ones most severely damaged; the lower front teeth
receive some protection from the tongue. Pacifiers
dipped in sugar, honey, corn syrup, or other sweetened
liquid also contribute to bottle-mouth syndrome. The
first signs of damage are chalky white spots or lines
across the teeth. As decay progresses, the damage to
the child’s teeth becomes obvious.

Tooth decay

Nerve

Cavity

Gum
Gingiva

Pulp

Bone

Periodontal
membrane

Normal tooth

Tooth with cavity

Tooth decay is the destruction of the outer surface, or enamel, of a tooth. It is caused by acid buildup from plaque bacteria, which
dissolves the minerals in the enamel and creates cavities. (Illustration by Electronic Illustrators Group.)

strategies include: proper oral hygiene; fluoride; sealants; and attention to diet.
Oral hygiene
GENERAL CARE OF THE MOUTH. The best way to
prevent tooth decay is to brush the teeth at least twice a
day, preferably after every meal and snack, and floss
daily. Cavities develop most easily in spaces that are
hard to clean. These areas include surface grooves,
spaces between teeth, and the area below the gum line.
Effective brushing cleans each outer tooth surface, inner
tooth surface, and the horizontal chewing surfaces of the
back teeth, as well as the tongue. Flossing once a day also
helps prevent gum disease by removing food particles
and plaque at and below the gum line, as well as between
teeth. Patients should visit their dentist every six months
for oral examination and professional cleaning.
MOUTH CARE IN OLDER ADULTS. Older adults who
have lost teeth or had them removed still need to maintain a clean mouth. Bridges and dentures must be kept
clean to prevent gum disease. Dentures should be
relined and adjusted by a dentist whenever necessary
to maintain proper fit. These adjustments help to keep
the gums from becoming red, swollen, and tender.
MOUTH CARE IN CHILDREN. Parents can easily prevent baby bottle tooth decay by not allowing a child to
fall asleep with a bottle containing sweetened liquids.

3722

Bottles should be filled only with plain, unsweetened
water. The child should be introduced to drinking
from a cup around six months of age and weaned
from bottles by twelve months. If an infant seems to
need oral comfort between feedings, a pacifier specially
designed for the mouth may be used. Pacifiers, however,
should never be dipped in honey, corn syrup, or other
sweet liquids. After the eruption of the first tooth, parents should begin routinely wiping the infant’s teeth and
gums with a moist piece of gauze or a soft cloth, especially right before bedtime. Parents may begin brushing
a child’s teeth with a small, soft toothbrush at about two
years of age, when most of the primary teeth have come
in. They should apply only a very small amount (the size
of a pea) of toothpaste containing fluoride. Too much
fluoride may cause spotting (fluorosis) of the tooth
enamel. As the child grows, he or she will learn to handle
the toothbrush, but parents should control the application of toothpaste and do the followup brushing until
the child is about seven years old.
Fluoride application
Fluoride is a natural substance that slows the
destruction of enamel and helps to repair minor
tooth decay damage by remineralizing tooth structure.
Toothpaste, mouthwash, fluoridated public drinking
water, and vitamin supplements are all possible
GALE ENCYCLOPEDIA OF MEDICINE

Amalgam—A mixture (alloy) of silver and several
other metals, used by dentists to make fillings for
cavities.
Caries—The medical term for tooth decay.
Cavity—A hole or weak spot in the tooth surface
caused by decay.
Dentin—The middle layer of a tooth, which makes
up most of the tooth’s mass.
Enamel—The hard, outermost surface of a tooth.
Fluoride—A chemical compound containing fluorine that is used to treat water or applied directly to
teeth to prevent decay.
Mucin—A protein in saliva that combines with
sugars in the mouth to form plaque.
Plaque—A thin, sticky, colorless film that forms on
teeth. Plaque is composed of mucin, sugars from
food, and bacteria that live in the plaque.
Pulp—The soft, innermost layer of a tooth containing blood vessels and nerves.
Sealant—A thin plastic substance that is painted
over teeth as an anti-cavity measure to seal out
food particles and acids produced by bacteria.
Transillumination—A technique of checking for
tooth decay by shining a light behind the patient’s
teeth. Decayed areas show up as spots or shadows.

sources of fluoride. Children living in areas without
fluoridated water should receive 0.5 mg/day of fluoride (0.25 mg/day if using a toothpaste containing
fluoride) from three to five years of age, and 1 mg/
day from six to12 years.
While fluoride is important for protecting children’s developing teeth, it is also of benefit to older
adults with receding gums. It helps to protect their
newly exposed tooth surfaces from decay. Older adults
can be treated by a dentist with a fluoride solution that
is painted onto selected portions of the teeth or poured
into a fitted tray and held against all the teeth.

because no part of the tooth is removed, although
the tooth surface is etched with acid so that the plastic
will adhere to the rough surface. Sealants are usually
clear or tooth-colored, making them less noticeable
than silver fillings. They cost less than fillings and
can last up to 10 years, although they should be
checked for wear at every dental visit. Children should
get sealants on their first permanent ‘‘6-year’’ molars,
which come in between the ages of five and seven, and
on the second permanent ‘‘12-year’’ molars, which
come in between the ages of 11 and 14. Sealants should
be applied to the teeth shortly after they erupt, before
decay can set in. Although sealants have been used in
the United States for about 25 years, one survey by the
National Institute of Dental Research reported that
fewer than 8% of American children have them.
Diet
The risk of tooth decay can be lowered by choosing foods wisely and eating less often. Foods high in
sugar and starch, especially when eaten between
meals, increase the risk of cavities. The bacteria in
the mouth use sugar and starch to produce the acid
that destroys the enamel. The damage increases with
more frequent eating and longer periods of eating. For
better dental health, people should eat a variety of
foods, limit the number of snacks, avoid sticky and
overly sweetened foods, and brush often after eating.
Drinking water is also beneficial for rinsing food
particles from the mouth. Children can be taught to
‘‘swish and swallow’’ if they are unable to brush after
lunch at school. Similarly, saliva stimulated during
eating makes it more difficult for food and bacteria
to stick to tooth surfaces. Saliva also appears to have a
buffering effect on the acid produced by the plaque
bacteria and to act as a remineralizing agent. Older
patients should be made aware that some prescription
medications may decrease salivary flow. Less saliva
tends to increase the activity of plaque bacteria and
encourage further tooth decay. Chewing sugarless
gum increases salivation and thus helps to lower the
risk of tooth decay.
Resources
ORGANIZATIONS

Sealants
Because fluoride is most beneficial on the smooth
surfaces of teeth, sealants were developed to protect
the irregular surfaces of teeth. A sealant is a thin
plastic coating that is painted over the grooves of
chewing surfaces to prevent food and plaque from
being trapped there. Sealant treatment is painless
GALE ENCYCLOPEDIA OF MEDICINE

American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.
American Dental Hygienists’ Association. 444 North
Michigan Ave., Chicago, IL 60611. (800)847-6718.
National Institute of Dental Research. 31 Center Drive,
MSC 2190, Building 31, Room 5B49, Bethesda, MD
20892-2190.
3723

Tooth decay

KEY TERMS

Tooth extraction

OTHER

Healthtouch Online Page. <http://www.healthtouch.com>.

Bethany Thivierge

Tooth extraction
Definition
Tooth extraction is the removal of a tooth from its
socket in the bone.

Purpose
Extraction is performed for positional, structural,
or economic reasons. Teeth are often removed because
they are impacted. Teeth become impacted when they
are prevented from growing into their normal position
in the mouth by gum tissue, bone, or other teeth.
Impaction is a common reason for the extraction of
wisdom teeth. Extraction is the only known method
that will prevent further problems. Teeth may also be
extracted to make more room in the mouth prior to
straightening the remaining teeth (orthodontic treatment), or because they are so badly positioned that
straightening is impossible. Extraction may be used to
remove teeth that are so badly decayed or broken that
they cannot be restored. In addition, patients sometimes choose extraction as a less expensive alternative
to filling or placing a crown on a severely decayed
tooth.

Precautions
In some situations, tooth extractions may need to
be postponed temporarily. These situations include:


Infection that has progressed from the tooth into the
bone. Infections may make anesthesia difficult. They
can be treated with antibiotics before the tooth is
extracted.



The patient’s use of drugs that thin the blood (anticoagulants). These medications include warfarin
(Coumadin) and aspirin. The patient should stop
using these medications for three days prior to
extraction.



Patients who have had any of the following procedures in the previous six months: heart valve replacement, open heart surgery, prosthetic joint
replacement, or placement of a medical shunt.

3724

These patients may be given antibiotics to reduce
the risk of bacterial infection.

Description
Tooth extraction can be performed with local
anesthesia if the tooth is exposed and appears to be
easily removable in one piece. An instrument called an
elevator is used to loosen (luxate) the tooth, widen the
space in the bone, and break the tiny elastic fibers that
attach the tooth to the bone. Once the tooth is dislocated from the bone, it can be lifted and removed with
forceps.
If the extraction is likely to be difficult, the dentist
may refer the patient to an oral surgeon. Oral surgeons
are specialists who are trained to give nitrous oxide, an
intravenous sedative, or a general anesthetic to relieve
pain. Extracting an impacted tooth or a tooth with
curved roots typically requires cutting through gum
tissue to expose the tooth. It may also require removing portions of bone to free the tooth. Some teeth must
be cut and removed in sections. The extraction site
may or may not require one or more stitches to close
the cut (incision).

Preparation
Before an extraction, the dentist will take the
patient’s medical history, noting allergies and prescription medications. A dental history is also taken,
with particular attention to previous extractions and
reactions to anesthetics. The dentist may then prescribe antibiotics or recommend stopping certain medications prior to the extraction. The tooth is x-rayed to
determine its full shape and position, especially if it is
impacted.
If the patient is going to have deep anesthesia, he
or she should wear loose clothing with sleeves that are
easily rolled up to allow for an intravenous line. The
patient should not eat or drink anything for at least six
hours before the procedure. Arrangements should be
made for a friend or relative to drive the patient home
after the surgery.

Aftercare
An important aspect of aftercare is encouraging a
clot to form at the extraction site. The patient should
put pressure on the area by biting gently on a roll or
wad of gauze for several hours after surgery. Once the
clot is formed, it should not be disturbed. The patient
should not rinse, spit, drink with a straw, or smoke for
at least 24 hours after the extraction and preferably
GALE ENCYCLOPEDIA OF MEDICINE

Dry socket—A painful condition following tooth
extraction in which a blood clot does not properly
fill the empty socket. Dry socket leaves the underlying bone exposed to air and food.
Extraction site—The empty tooth socket following
removal of the tooth.
Impacted tooth—A tooth that is growing against
another tooth, bone, or soft tissue.
Luxate—To loosen or dislocate the tooth from the
socket.

A close-up view inside a person’s mouth following the
extraction of the lower right molar. (Custom Medical Stock
Photo. Reproduced by permission.)

longer. Vigorous exercise should not be done for the
first three to five days.
For the first two days after the procedure, the
patient should drink liquids without using a straw,
and eat soft foods. Any chewing must be done on the
side away from the extraction site. Hard or sticky
foods should be avoided. The mouth may be gently
cleaned with a toothbrush, but the extraction area
should not be scrubbed.
Wrapped ice packs can be applied to reduce facial
swelling. Swelling is a normal part of the healing process. It is most noticeable in the first 48–72 hours. As
the swelling subsides, the patient may experience muscle stiffness. Moist heat and gentle exercise will restore
jaw movement. The dentist may prescribe medications
to relieve the postoperative pain.

Risks
Potential complications of tooth extraction
include postoperative infection, temporary numbness
from nerve irritation, jaw fracture, and jaw joint pain.
An additional complication is called dry socket. When
a blood clot does not properly form in the empty tooth
socket, the bone beneath the socket is painfully
exposed to air and food, and the extraction site heals
more slowly.

Normal results
After an extraction, the wound usually closes in
about two weeks. It takes three to six months for the
bone and soft tissue to be restructured. Complications
GALE ENCYCLOPEDIA OF MEDICINE

Nitrous oxide—A colorless, sweet-smelling gas
used by dentists for mild anesthesia. It is sometimes
called laughing gas because it makes some patients
feel giddy or silly.
Oral surgeon—A dentist who specializes in surgical procedures of the mouth, including extractions.
Orthodontic treatment—The process of straightening teeth to correct their appearance and function.

such as infection or dry socket may prolong the healing time.
Resources
ORGANIZATIONS

American Association of Oral and Maxillofacial Surgeons.
9700 West Bryn Mawr Ave., Rosemont, IL 60018-5701.
(847) 678-6200. <http://www.aaoms.org>.

Bethany Thivierge

Tooth grinding see Bruxism

Tooth replacements and
restorations
Definition
A tooth restoration is any artificial substance or
structure that replaces missing teeth or part of a tooth
in order to protect the mouth’s ability to eat, chew,
and speak. Restorations include fillings, inlays,
crowns, bridges, partial and complete dentures, and
dental implants.
3725

Tooth replacements and restorations

KEY TERMS

Tooth replacements and restorations

Purpose
Restorations have somewhat different purposes
depending on their extensiveness. Fillings, inlays, and
crowns are intended to repair damage to individual
teeth. They replace tooth structure lost by decay or
injury, protect the part of the tooth that remains, and
restore the tooth’s shape and function. Bridges, dentures, and implants are intended to protect the shape
and function of the mouth as a whole.

Precautions
Some patients are allergic to the medications used
for local anesthesia in dental restorations. In addition,
many people in the general population are afraid of
dental work. Most dentists in present-day practice can
help patients with this specific fear.

Description
Fillings
Fillings are restorations that are done to repair
damage caused by tooth decay (dental caries). Tooth
decay occurs when microorganisms in the mouth convert sugar from food to acid, which attacks the tooth.
The acid forms cavities that start in the hard outer
surface of the tooth (the enamel) and may extend
inward to the pulp, which contains the tooth’s nerves
and blood vessels. Left untreated, tooth decay may
lead to inflammation and infection that may cause
toothache and perhaps more serious complications.
To stop the decay process, the dentist removes the
decayed portion of the tooth using a high-speed drill or
an air abrasion system, shapes the cavity walls, and
replaces the tooth structure with a filling of silver amalgam, composite resin, or gold. The filling is placed in the
cavity as a liquid or soft solid. It sets within a few
minutes and continues to harden over the next several
hours. Silver amalgam is commonly used to fill cavities
on the biting surfaces of the back teeth, because it is
strong enough to withstand the tremendous pressures
exerted by grinding and chewing. Composite resin is
typically used to fill cavities in front teeth and any
other teeth that are visible when the patient smiles,
because its color can be matched to the tooth surface.
Gold as a filling material is far less common, but is being
increasingly used. Although it is more expensive and
less easily applied, it does not trigger the sensitivity
reactions that some patients have to silver amalgam.
Inlays
An inlay resembles a filling in that it fills the space
remaining after the decayed portion of a tooth has
3726

been removed. The difference is that an inlay is shaped
outside the patient’s mouth and then cemented into
place. After the decay is removed and the cavity walls
are shaped, the dentist makes a wax pattern of the
space. A mold is cast from the wax pattern. An inlay,
usually of gold, is made from this mold and sealed into
the tooth with dental cement.
Crowns
The crown of a tooth is the portion that is covered
by enamel. A restorative crown replaces this outer part
to protect the tooth. This protection becomes necessary when a tooth cracks or has its entire structure
weakened by decay. As with a filling or inlay, the
dentist first removes the decayed portion of the
tooth. The tooth is then prepared for a crown. It may
be tapered on the outside edges to a peg, reinforced
with a cast metal core, or rebuilt with both a cast metal
core and a post. A wax impression of the prepared
tooth and the teeth next to it is made. The new crown is
made to fit this mold. The crown may be made of gold
or stainless steel alone, metal with a veneer of toothcolored porcelain or resin, or of porcelain or resin
alone. The finished crown is then placed over the prepared tooth, adjusted, and cemented into place.
Bridges
Bridges are a type of restoration that is done when
one or more permanent teeth are lost or pulled. The
resulting gap must be filled in to prevent the remaining
teeth from shifting. If the other teeth shift, they will
affect the patient’s bite (occlusion), which sometimes
produces pain in the jaw joint. As the teeth move and
become crooked, they also become more difficult to
keep clean. The risk of tooth decay and gum disease
increases, increasing the likelihood that additional
teeth will be lost. A bridge is inserted to prevent this
risk. Bridges are nonremovable appliances of one or
more artificial teeth (pontics) anchored by crowns on
the adjacent teeth (abutment teeth). The abutment
teeth carry the pressure when the patient chews food.
Partial dentures
A partial denture is similar to a bridge in that it
fills a gap left by missing teeth with artificial teeth on a
metal frame. A partial denture is removable, however.
It attaches to a crown on the abutment tooth with a
metal clasp or precision attachment. A partial denture
is primarily used at the end of a row of natural teeth,
where there is only one abutment tooth. The pressure
exerted by chewing is shared by this abutment and the
soft tissues of the gum ridge beneath the appliance.
GALE ENCYCLOPEDIA OF MEDICINE

Complete dentures may be worn when all of the
top or bottom teeth have been lost. A complete denture consists of artificial teeth mounted in a plastic
base molded to fit the remaining oral anatomy. It
may or may not be held in place with a denture
adhesive.
Implants
Dental implants are a means of securing crowns,
bridges, and dentures in the mouth. A hard plastic or
metal fixture is implanted through the soft tissue into
the bone. Over time, the bone grows around this fixture, firmly anchoring it. The exposed end of this
fixture is covered with a crown and may serve as a
stable abutment for a bridge or denture.

Preparation
Before a restoration is placed in the mouth, the
dentist removes all traces of decay and shapes the
remaining tooth structure for the restoration. Fillings
are the only restoration created within the tooth itself–
the others are made up in a laboratory using a model
of the tooth structure. Thus, a filling may be placed in
a single dental visit, while the other restorations
usually take several appointments. Temporary crowns
and dentures are put in place after the tooth is shaped
until the permanent restoration is delivered by the
laboratory.

Aftercare

KEY TERMS
Abutment tooth—A crowned tooth that stabilizes a
bridge or partial denture.
Bridge—An appliance of one or more artificial
teeth anchored by crowns on the adjacent teeth.
Complete denture—A full set of upper or lower
teeth, mounted in a plastic base. Dentures are
also called false teeth.
Crown—A protective shell that fits over the tooth.
Dental caries—A disease of the teeth in which
microorganisms convert sugar in the mouth to
acid that erodes the tooth.
Enamel—The hard outermost surface of a tooth.
Filling—Dental material that occupies the space
remaining within a tooth after the decayed portion
has been removed.
Implant—A fixture with one end implanted into the
bone and the other end covered with a crown, often
to serve as a stable abutment for a bridge or
denture.
Inlay—A filling that is made outside of the tooth
and the cemented into place.
Occlusion—The way upper and lower teeth fit
together during biting and chewing.
Partial denture—A removable bridge that usually
clasps onto only one abutment.
Pontic—An artificial tooth.
Pulp—The soft innermost layer of a tooth that contains its blood vessels and nerves.

Fillings
Fillings need time to harden for several hours after
being placed, so the patient should chew food on the
opposite side of the mouth for the first day.
Dentures
A partial or complete denture may take several
weeks of getting used to. Inserting and removing the
denture will take practice. Speaking clearly may be
difficult at first–the patient may find it helpful to
read out loud for practice. Eating may also feel awkward. The patient should begin by eating small pieces
of soft foods. Very hard or sticky foods should be
avoided.
Patients with dentures must work on good oral
hygiene. Specialty brushes and floss threaders may be
used to remove plaque and food from around crowns
and bridges. Dentures should be removed and brushed
GALE ENCYCLOPEDIA OF MEDICINE

daily with a specially designed brush and a denture
cleaner or other mild soap.
The patient should see the dentist for an adjustment if there is any discomfort or irritation resulting
from a restoration. Otherwise, the patient should
see the dentist at least twice a year for an oral
examination.

Risks
Restoration procedures typically require local
anesthesia. Some people may have allergic reactions
to the medication. A very small number of people are
allergic to one or more of the metals used in a dental
restoration. In most cases, the dentist can use another
material.
3727

Tooth replacements and restorations

Complete dentures

Toothache

Normal results
A well-made restoration should feel comfortable
and last a relatively long time with proper care.
Artificial dental restorations only approximate the original tooth, however. A complete denture will never feel
as comfortable or work as well as natural teeth. It is
better, therefore, to prevent the need for restorative
dental work than to replace teeth. Restorations are
expensive, may require many appointments, and still
need careful cleaning and attention.



cracked or impacted tooth



exposed tooth root



food wedged between teeth or trapped below the
gum line



tooth nerve irritated by clenching or grinding of teeth
(bruxism)



pressure from congested sinuses



traumatic injury

Resources

Diagnosis

ORGANIZATIONS

Academy of General Dentistry. Suite 1200, 211 East
Chicago Ave., Chicago, IL 60611. (312) 440-4300.
<http://www.agd.org>.
American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.

Bethany Thivierge

Toothache
Definition
A toothache is any pain or soreness within or
around a tooth, indicating inflammation and possible
infection.

Diagnosis includes identifying the location of the
toothache, as well as the cause. The dentist begins by
asking the patient specific questions about the toothache, including the types of foods that make the pain
worse, whether the tooth is sensitive to temperature or
biting, and whether the pain is worse at night. The
dentist then examines the patient’s mouth for signs of
swelling, redness, and obvious tooth damage. The presence of pus indicates an abscess or gum disease. The
dentist may flush the sore area with warm water to
dislodge any food particles and to test for sensitivity
to heat. The dentist may then dry the area with gauze
to determine sensitivity to touch and pressure. The
dentist may probe tooth crevices and the edges of fillings with a sharp instrument, looking for areas of tooth
decay. Finally, the dentist may take x rays, looking for
evidence of decay between teeth, a cracked or impacted
tooth, or a disorder of the underlying bone.

Treatment
Description
A toothache may feel like a sharp pain or a dull
ache. The tooth may be sensitive to pressure, heat,
cold, or sweets. In cases of severe pain, identifying
the problem tooth is often difficult. Any patient with
a toothache should see a dentist at once for diagnosis
and treatment. Most toothaches get worse if not
treated.

Causes and symptoms
Toothaches may result from any of a number of
causes:


tooth decay (dental caries)



inflammation of the tooth pulp (pulpitis)



abscesses



gum disease, including periodontitis



loose or broken filling

3728

Emergency self-care
Toothaches should always be professionally treated by a dentist. Some methods of self-treatment, however, may help manage the pain until professional care
is available:


rinsing with warm salt water



using dental floss to remove any food particles



taking aspirin or acetaminophen (Tylenol) to relieve
pain; the drug should be swallowed–never placed
directly on the aching tooth or gum



applying a cold compress against the outside of the
cheek; do not use heat, because it will tend to spread
infection.



using clove oil (Syzygium aromaticum) to numb the
gums; the oil may be rubbed directly on the sore area
or used to soak a small piece of cotton and applied to
the sore tooth
GALE ENCYCLOPEDIA OF MEDICINE

Abscess—A hole in the tooth or gum tissue filled
with pus as the result of infection.
Bruxism—Habitual clenching and grinding of the
teeth as a result of stress. The behavior usually
occurs during sleep.
Cavity—A hole or weak spot in the tooth surface
caused by decay.
Dental caries—A disease of the teeth in which
microorganisms convert sugar in the mouth to
acid, which then erodes the tooth.
Enamel—The hard outermost surface of a tooth.
Endodontist—A dentist who specializes in diagnosing and treating diseases of the pulp and other
inner parts of the tooth.
Impacted tooth—A tooth that is growing against
another tooth, bone, or soft tissue.
Periodontitis—A gum disease that destroys the
structures supporting the teeth, including bone.
Pulp—The soft innermost part of a tooth, containing blood vessels and nerves.
Pulpitis—Inflammation of the pulp of a tooth that
involves the blood vessels and nerves.

or over a hole in the tooth. The herb corydalis
(Corydalis yanhusuo) may also help relieve toothache
pain. Pain also may be reduced using acupressure,
acupuncture, or reiki. Acupuncture should be done
only by a licensed practitioner.

Prognosis
Prompt dental treatment provides a positive outcome for toothache. In the absence of active infection,
fillings, root canal treatments, or extractions may be
performed with minimal discomfort to the patient.
When a toothache is left untreated, a severe infection
may develop and spread to the sinuses or jawbone, and
eventually cause blood poisoning.

Prevention
Maintaining proper oral hygiene is the key to preventing toothaches. The best way to prevent tooth
decay is to brush at least twice a day, preferably after
every meal and snack. Flossing once a day also helps
prevent gum disease by removing food particles and
bacteria at and below the gum line, as well as between
teeth. People should visit their dentist at least every six
months for oral examinations and professional
cleaning.
Resources
ORGANIZATIONS

Professional care
Treatment will depend on the underlying cause of
the toothache. If the pain is due to tooth decay, the
dentist will remove the decayed area and restore the
tooth with a filling of silver amalgam or composite
resin. Loose or broken fillings are removed, new decay
cleaned out, and a new filling is placed. If the pulp of
the tooth is damaged, root canal therapy is needed.
The dentist or a specialist called an endodontist
removes the decayed pulp, fills the space left behind
with a soothing paste, and covers the tooth with a
crown to protect and seal it. If the damage cannot be
treated by these methods, or if the tooth is impacted,
the tooth must be extracted.

Alternative treatment
Toothaches caused by infection or tooth decay
must be treated by a dentist. Several alternative therapies may be helpful for pain relief until dental treatment is available. Clove oil (Syzygium aromaticum)
may be rubbed on sensitive gums to numb them or
added to a small cotton pellet that is then placed into
GALE ENCYCLOPEDIA OF MEDICINE

Academy of General Dentistry. Suite 1200, 211 East
Chicago Ave., Chicago, IL 60611. (312) 440-4300.
<http://www.agd.org>.
American Dental Association. 211 E. Chicago Ave.,
Chicago, IL 60611. (312) 440-2500. <http://
www.ada.org>.
OTHER

Medical Source. Medical Alliances, Inc. 2121 Eisenhower
Ave.,Suite 603, Alexandria, VA 22314. (800) 463-6482
<http://www.medsource.com>.

Bethany Thivierge

Topical anesthesia
Definition
Topical anesthesia is a condition of temporary
numbness caused by applying a substance directly to
a surface of the body. Loss of feeling occurs in the
specific areas touched by the anesthetic substance.
3729

Topical anesthesia

KEY TERMS

Topical anesthesia

Purpose
Topical anesthesia typically either relieves existing
pain from a body surface or prevents pain during
medical examinations or procedures. Body surfaces
include both skin and mucous membranes, which are
the moist linings of areas such as the inside of the
mouth or nose. Occasionally, use of a topical anesthetic may help clarify whether a patient’s pain comes
from a body surface, which the substance is able to
touch, or from deeper structures beyond the reach of
the substance. A mucous membrane, an area of skin,
or areas just beneath the skin’s surface temporarily
lose feeling during topical anesthesia.

Precautions
Topical anesthetic medications must be selected
carefully and used in proper amounts in order to prevent harmful reactions. For instance, some topical
drugs should be used only on intact skin to avoid
rapid absorption into the body. Therefore, it is important to choose the right type and dosage of anesthetic
for each specific purpose.

Description
Most drugs in the early 2000s used to cause topical
anesthesia have at least some chemical similarity to
cocaine, which was recognized as a topical anesthetic
in the early 1900s. These drugs work by blocking nerve
impulses that carry pain messages to the brain.
Commonly used, twenty-first-century drugs include
benzocaine, lidocaine, prilocaine, and tetracaine,
These drugs come in several application forms, such
as cream, jelly, ointment, solution, and spray, are
available in varying strengths, and may be used alone
or in combinations.
One common use for topical anesthetics is to
relieve pain from problems such as sores in the
mouth, skin scrapes, and hemorrhoids. A person typically applies a cream or jelly to the affected area.
Numbness begins within a few minutes, and the anesthetic effect may last an hour or more. Repeated
applications are often necessary.
The other broad category of use for topical anesthetics is to prevent pain from medical examinations
or procedures on areas such as the eye, nose, throat,
urethra, rectum, or skin. For example, even a single
drop of anesthetic may allow examination of a painfully irritated eye or removal of a speck of dirt from the
eye surface. Careful inspection of a nostril or insertion
of a urinary drainage tube into the urethra may be
3730

KEY TERMS
Anesthetic—Not having sensation; related to the
loss of sensation; or, a substance that produces
loss of sensation.
EMLA—Eutectic mixture of local anesthetics, a
drug combination for use on intact skin.
LET—A topical anesthetic mixture containing lidocaine, epinephrine, and tetracaine.
Mucous membranes—Moist linings of body surfaces such as the inside of the mouth or nose.
Numbness—Loss of feeling or sensation.
TAC—A topical anesthetic mixture containing tetracaine, epinephrine (adrenaline), and cocaine.
Topical—For use directly on a body surface.

difficult or impossible without the use of topical anesthetic spray or jelly beforehand.
Many uses of topical anesthetics involve application to the skin. Physicians and patients have long
hoped for a way to numb an area of skin without
having to use a needle to inject anesthetic. Original
topical anesthetics were not effective in this way. A
newer drug preparation called eutectic mixture of local
anesthetics (EMLA, lidocaine 2.5%, and prilocaine
2.5%) can be used as a cream on intact skin. When
applied for about 60 minutes, EMLA numbs the skin
and penetrates as far as 5 mm below the surface.
EMLA may help patients by decreasing the pain of
needle pricks or simple skin procedures, such as repair
of small lacerations. The main drawback to EMLA is
that it takes so long for the anesthetic effect to begin,
thus reducing its usefulness in settings such as the
emergency rooms. Other drug combinations such as
tetracaine, epinephrine (adrenaline), and cocaine
(TAC), or lidocaine, epinephrine, and tetracaine
(LET) have their own advantages and disadvantages.
The application of ice to a body area is a primitive
method of producing topical anesthesia. Chemicals
such as ethyl chloride can be sprayed onto intact skin
to produce a momentary freezing and numbing effect.
Covering the ointment with plastic wrap increases
the absorption of the ointment through the skin. The
use of plastic wrap, or other occlusive dressings, is the
standard means of applying EMLA cream. Other
techniques include using gentle heat or electric current
to help the drugs penetrate intact skin.
GALE ENCYCLOPEDIA OF MEDICINE

Overall, topical anesthesia tends to be very safe.
Minor problems might include discoloration of the
skin at the application site or an uncomfortable feeling
of numbness that lasts longer than expected. Repeated
use of a topical anesthetic on a damaged eye surface
may interfere with the normal healing process. Rarely,
too much of the drug may be absorbed into the body in
a short time and cause a reaction such as seizure or
rapid heartbeat. Death related to topical anesthesia is
extremely rare.

Normal results
Successful use of a topical anesthetic produces
temporary loss of sensation in the area where it is
applied.
Resources
BOOKS

Hardman, Joel G., and Lee E. Limbird, eds. Goodman &
Gilman’s Pharmacologic Basis of Therapeutics. 10th ed.
New York: McGraw-Hill, 2001.
Miller, Ronald D., ed. Miller’s Anesthesia. 6th ed.
Philadelphia: Elsevier/Churchill Livingstone, 2005.
PERIODICALS

Kundu, Suriti. ‘‘Principles of Office Anesthesia: Part II.
Topical Anesthesia.’’ American Family Physician 66,
no. 1 (July 2002): 99–102.

infections: toxoplasmosis, other infections, rubella,
cytomegalovirus (CMV), and herpes simplex virus
(HSV). The ‘‘other infections’’ usually include syphilis,
hepatitis B, coxsackie virus, Epstein-Barr virus, varicella-zoster virus, and human parvovirus.
Since the TORCH test is a screening or first-level
test, the pediatrician may order tests of other body
fluids or tissues to confirm the diagnosis of a specific
infection. In the case of toxoplasmosis, rubella, and
syphilis, cerebrospinal fluid may be obtained from
the infant through a spinal tap in order to confirm
the diagnosis. In the case of CMV, the diagnosis is
confirmed by culturing the virus in a sample of the
infant’s urine. In HSV infections, tissue culture is the
best method to confirm the diagnosis.

Purpose
The five categories of organisms whose antibodies
are measured by the TORCH test are grouped
together because they can cause a cluster of symptomatic birth defects in newborns. This group of defects
is sometimes called the TORCH syndrome. A newborn baby with these symptoms will be given a
TORCH test to see if any of the five types of infection
are involved.
The symptoms of the TORCH syndrome include:


Small size in proportion to length of the mother’s
pregnancy at time of delivery. Infants who are smaller than would be expected (below the tenth percentile) are referred to as small-for-gestational-age,
or SGA.



Enlarged liver and spleen



Low level of platelets in the blood



Skin rash. The type of skin rash associated with the
TORCH syndrome is usually reddish-purple or
brown and is caused by the leakage of blood from
broken capillaries into the baby’s skin.



Involvement of the central nervous system. These
defects can include encephalitis, calcium deposits in
the brain tissue, and seizures.



Jaundice. The yellowish discoloration of the skin and
whites of the eyes due to liver disease.

Kenneth J. Berniker, M.D.
Abigail V. Berniker, B.A.

Topical antibiotics see Antibiotics, topical
Topical antifungal drugs see Antifungal
drugs, topical

TORCH test
Definition
The TORCH test, which is sometimes called the
TORCH panel, belongs to a category of blood tests
called infectious-disease antibody titer tests. This type
of blood test measures the presence of antibodies
(protein molecules produced by the human immune
system in response to a specific disease agent) and their
level of concentration in the blood. The name of the
test comes from the initial letters of the five disease
categories. The TORCH test measures the levels of an
infant’s antibodies against five groups of chronic
GALE ENCYCLOPEDIA OF MEDICINE

In addition to these symptoms, each of the
TORCH infections has its own characteristic symptom cluster in newborns:
Toxoplasmosis
Toxoplasmosis is caused by Toxoplasma gondii, a
parasite that the mother can acquire from handling
3731

TORCH test

Risks

TORCH test

infected cats, drinking unpasteurized milk, or eating
contaminated meat. The infection is carried to the
infant through the mother’s placenta, and can cause
infections of the eyes or central nervous system. The
organism can invade brain or muscle tissue and form
tissue cysts. The later in pregnancy that the mother is
infected, the higher the probability that the fetus will
be infected. On the other hand, toxoplasmosis early in
pregnancy is more likely to cause a miscarriage or
serious birth defects. The incidence of toxoplasmosis
in newborns is one in 1,000 live births.
Other (syphilis)
Syphilis is caused by a spirochete (spiral- or coilshaped bacterium), Treponema pallidum. It is transmitted in the adult population by sexual intercourse.
About 2-5% of children born to mothers diagnosed
with syphilis will have the disease at birth. Syphilis
was added to the TORCH panel because of a rapid
increase in reported cases since 1990. It is also a
potentially life-threatening infection for the fetus.
Syphilis can cause early delivery, miscarriage, or stillbirth. The mortality rate in infants infected with
syphilis is about 54%.
Rubella
Rubella is a virus that has a seasonal pattern, with
epidemics most likely in the spring. Between 0.1-2% of
newborns will be infected with rubella. The rate of
fetal infection varies according to the timing of the
mother’s infection during pregnancy. Birth defects,
however, are most likely (85%) in infants infected
during the first eight weeks of pregnancy. Infants
born with rubella may already show signs of heart
disease, retarded growth, hearing loss, blood disorders, vision problems, or pneumonia. They may also
develop problems later in childhood, including autism,
hearing loss, brain syndromes, immune system disorders, or thyroid disease.
Cytomegalovirus (CMV)
Cytomegalovirus belongs to the herpesvirus
group of infections. It can be transmitted through
body secretions, as well as by sexual contact; some
newborns acquire CMV through the mother’s
breast milk. In adults, it produces symptoms resembling those of mononucleosis. About 1–2.2% of
newborns in the United States are infected with
CMV. Of this group, 10% will have measurable
symptoms. The mortality rate for these symptomatic newborns is 20–30%. Surviving infants with
CMV may suffer from hearing problems (15%) or
3732

mental retardation (30%). Newborns that acquire
CMV during the birth process or shortly after
birth may develop pneumonia, hepatitis, or various
blood disorders.
Herpes simplex virus (HSV)
Herpesvirus infections are among the most common viral infections in humans. They are spread by
oral, as well as genital, contact. It is estimated that
between 1 in 1,000 and 1 in 5,000 infants are born with
HSV infections. About 80% of these infections are
acquired during the birth process itself; the virus enters
the infant through its eyes, skin, mouth, and upper
respiratory tract. Of infants born with HSV infection,
about 20% will have localized infections of the eyes,
mouth, or skin. About 50% of infected infants will
develop disease spread throughout the body (disseminated) within nine to 11 days after birth. Disseminated
herpes infections attack the liver and adrenal glands,
as well as other body organs. Without treatment, the
mortality rate is 80%. Even with antiviral medication,
the mortality rate is still 15–20%, with 40–55% of the
survivors having long-term damage to the central nervous system. It is critical for the doctor to diagnose
HSV infection in the newborn as soon as possible, for
effective treatment.

Description
The TORCH panel requires a sample of the
infant’s blood. Samples from infants are usually
obtained by the heelstick procedure when only a
small quantity of blood is needed. The baby’s foot is
wrapped in a warm cloth for five minutes, to make the
blood flow more easily. The foot is then wiped with an
alcohol swab and a lancet is used to stick the baby’s
heel on one side. It is important to avoid the center of
the heel, in order to prevent an inflammation of the
bone.

Preparation
No special preparation, other than sterile technique, is required.

Risks
The only complications associated with the
TORCH test are those resulting from the heelstick
technique itself. These risks include scarring, infection
of the bone, cellulitis (inflammation of cellular tissue),
small lumpy calcium deposits, and inaccurate test
results.
GALE ENCYCLOPEDIA OF MEDICINE

Antibody—A protein molecule produced by the
immune system that is specific to a disease agent,
such as CMV and the other organisms sought by the
TORCH test. The antibody combines with the
organism and disables it.
Perinatal—Referring to the period of time surrounding an infant’s birth, from the last two months
of pregnancy to the first 28 days of life. The TORCH
panel tests for perinatal infections.
Small-for-gestational-age (SGA)—A term used to
describe newborns who are below the 10th percentile in height or weight for their estimated gestational age. The gestational age is based upon the
date of the mother’s last menstrual period. SGA is
one of the symptoms of TORCH syndrome.
Titer—The concentration of a substance in a given
sample of blood or other tissue fluid.

Normal results
The normal result would be normal levels of
immunoglobulin M (IgM) antibody in the infant’s
blood. IgM is one of five types of protein molecules
found in blood that function as antibodies. IgM is a
specific class of antibodies that seeks out virus particles. In contrast to adults, IgM is the most common
type of immunoglobulin in newborn children. It is,
therefore, the most useful indicator of the presence of
a TORCH infection.

Abnormal results
The general abnormal, or positive, finding would
be high levels of IgM antibody. The test can be refined
further for antibodies specific to given disease agents.
The TORCH screen, however, can produce both falsepositive and false-negative findings. Doctors can measure IgM levels in the infant’s cerebrospinal fluid, as
well as in the blood, if they want to confirm the
TORCH results.

Torticollis

KEY TERMS

Torticollis
Definition
Torticollis (cervical dystonia or spasmodic torticollis) is a type of movement disorder in which the
muscles controlling the neck cause sustained twisting
or frequent jerking.

Description
In torticollis, certain muscles controlling the neck
undergo repetitive or sustained contraction, causing
the neck to jerk or twist to the side. Cervical dystonia
causes forward twisting, and is called antecollis.
Backward twisting is known as retrocollis. The abnormal posture caused by torticollis is often debilitating,
and is usually painful.
Torticollis most commonly begins between age
30–60, with females affected twice as often as males.
According to the National Spasmodic Torticollis
Association, torticollis affects 83,000 people in the
United States. Dystonia tends to become more severe
during the first months or years after onset, and may
spread to other regions, especially the jaw, arm, or leg.
Torticollis should not be confused with such other
causes of abnormal neck posture as orthopedic or
congenital problems.

Causes and symptoms
The nerve signals responsible for torticollis are
thought to originate in the basal ganglia, a group of
brain structures involved in movement control. The
exact defect is unknown. Some cases of dystonia are
due to the inheritance of a defective gene, whose
function was unknown as of mid-1998. Other cases
are correlated with neck or head trauma, such
as from an automobile accident. Use of certain
antipsychotic drugs, or neuroleptics, can induce
dystonia.
There are three types of torticollis:


tonic, in which the abnormal posture is sustained



clonic, marked by jerky head movements.

Resources



mixed, a combination of tonic and clonic movements

BOOKS

Symptoms usually begin gradually, and may be
intermittent at first, worsening in times of stress.
Symptoms usually progress over two to five years,
and then remain steady. Symptoms may be relieved
somewhat when lying down. Many people with torticollis can temporarily correct their head position by
sensory tricks, as touching the chin or cheek on the

Levin, Myron J. ‘‘Infections: Viral & Rickettsial.’’ In
Current Pediatric Diagnosis & Treatment, edited by
William W. Hay Jr., et al. Stamford: Appleton & Lange,
1997.

Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

3733

Total parenteral nutrition

side opposite the turning. The reason for the effectiveness of this ‘‘geste antagoniste,’’ as it is called, is
unknown.
Pain in the neck, back, or shoulder affects more
than two-thirds of all people with torticollis. Pain may
spread to the arm or hand.

Diagnosis
Diagnosis of torticollis is aided by an electrical
study (electromyography) that can detect overactive
muscles. Imaging studies, including x rays, may be
done to rule out other causes of abnormal posture. A
detailed medical history is needed to determine possible causes, including trauma.

Treatment
A variety of oral drugs are available to relax muscles, including baclofen. For a subgroup of patients,
L-dopa provides effective relief. Denervation of the
involved neck muscles may be performed with injection of alcohol or phenol on to the nerve.
Injection of botulinum toxin (BTX) is considered
by many to be the treatment of choice. By preventing
release of chemical messages from the nerve endings
that stimulate the involved muscles, BTX partially
paralyzes the muscles, therefore allowing more normal
posture and range of motion. BTX treatment lasts
several months, and may be repeated.
Physical therapy can help relieve secondary
consequences of torticollis. Regular muscle stretching prevents contracture, or permanent muscle
shortening. Pain and spasm may be temporarily
lessened with application of heat or ice. Stress management techniques may help prevent worsening.
An occupational therapist can suggest home or
work modifications to reduce fatigue and improve
function. Braces constructed to replace the patient’s
own sensory tricks may help reduce abnormal
posture.

Alternative treatment
Biofeedback may be effective for some patients.
Regular massage therapy can reduce additional pain
in compensating areas of the body. Two energy-based
therapies, acupuncture and homeopathic medicine,
can work to rebalance the whole person, helping to
correct the torticollis. Antispasmodic herbs may help
to relax the muscles. In addition, herbs that can help
balance the stimulus from the nervous system are
often recommended.
3734

Prognosis
Spontaneous remission is seen in up to 20% of
patients, most often those patients with older onset
and milder symptoms. Dystonia may spread to affect
other regions of the body.

Prevention
There is no way known to prevent torticollis.
Resources
ORGANIZATIONS

National Spasmodic Torticollis Association. P.O. Box 5849,
Orange, CA 92863-5849. (800) 487-8385. <http://
www.bluheronweb.com>.
Worldwide Education and Awareness for Movement
Disorders. One Gustave L. Levy Place, Box 1052,
New York, NY 10029. (800) 437-6683. <http://
www.wemove.org>.

Richard Robinson

Total parenteral nutrition
Definition
Total parenteral nutrition (TPN) is a way of supplying all the nutritional needs of the body by bypassing the digestive system and dripping nutrient solution
directly into a vein.

Purpose
TPN is used when individuals cannot or should
not get their nutrition through eating. TPN is used
when the intestines are obstructed, when the small
intestine is not absorbing nutrients properly, or a gastrointestinal fistula (abnormal connection) is present.
It is also used when the bowels need to rest and not
have any food passing through them. Bowel rest may
be necessary in Crohn’s disease, pancreatitis, ulcerative
colitis, and with prolonged bouts of diarrhea in young
children. TPN is also used for individuals with severe
burns, multiple fractures, and in malnourished individuals to prepare them for major surgery, chemotherapy, or radiation treatment. Individuals with AIDS
or widespread infection (sepsis) may also benefit
from TPN.
GALE ENCYCLOPEDIA OF MEDICINE

Individuals need to tell their doctor if they have
any allergies, what medications they are taking, if they
are diabetic, have had liver, kidney, heart, lung, or
hormonal disorders, and if they are pregnant. All
these factors can affect the type and amount of TPN
required.

Description
TPN is normally given through a large central
vein. A catheter is inserted into the vein in the chest
area under local anesthesia and sterile conditions.
Often the placement is done in an operating room to
decrease the chance of infection. Several different
types catheters are used based on the reason TPN is
needed and the expected length of treatment.
Catheters are made of silicone. Once the catheter is
in place, a chest x ray is done to make sure the placement is correct.
Normally TPN is administered in a hospital, but
under certain conditions and with proper patient and
caregiver education, it may also be used at home for
long-term therapy. TPN solution is mixed daily under
sterile conditions. Maintaining sterility is essential for
preventing infection. For this reason, the outside tubing leading from the bag of solution to the catheter is
changed daily, and special dressings covering the
catheter are changed every other day.
The contents of the TPN solution are determined
based on the age, weight, height, and the medical
condition of the individual. All solutions contain
sugar (dextrose) for energy and protein (amino
acids). Fats (lipids) may also be added to the solution.
Electrolytes such as potassium, sodium, calcium, magnesium, chloride, and phosphate are also included, as
these are essential to the normal functioning of the
body. Trace elements such as zinc, copper, manganese
and chromium are also needed. Vitamins can be
included in the TPN solution, and insulin, a hormone
that helps the body use sugar, may need to be added.
The TPN catheter is used only for nutrients; medications are not added to the solution. Adults need
approximately 2 liters of TPN solution daily, although
this amount varies with the age, size, and health of the
individual. Special solutions have been developed for
individuals with reduced liver and kidney function.
The solution is infused slowly at first to prevent fluid
imbalances, then the rate is gradually increased. The
infusion process takes several hours.
Successful TPN requires frequent, often daily
monitoring of the individual’s weight, glucose (blood
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Catheter—A hollow tube that is inserted into veins
or other passages in the body to insert or remove
fluid.
Electrolyte—An ion such as potassium sodium, or
chloride dissolved in fluid that helps to regulate
metabolic activities of the cell.
Fistula—An abnormal passage that connects one
organ to another or that connects the organ to the
outside of the body.

sugar) level, blood count, blood gasses, fluid balance,
urine output, waste products in the blood (plasma
urea) and electrolytes. Liver and kidney function
tests may also be performed. The contents of the
solution are individualized based on the results of
these tests.

Preparation
Preparation to insert the catheter involves creating a sterile environment. Other special preparations
are not normally necessary.

Aftercare
During the time the catheter is in place, patients
and caregivers must be alert to any signs of infection
such as redness, swelling, fever, drainage, or pain.

Risks
TPN requires close monitoring. Two types of
complications can develop. Infection, air in the lung
cavity (pneumothorax) and blood clot formation
(thrombosis) all can develop as a result of inserting
the catheter into a vein. Metabolic and fluid imbalances can occur if the contents of the nutritional fluid
are not properly balanced and monitored. The most
common metabolic imbalance is hypoglycemia, or low
blood sugar, caused by abruptly discontinuing a solution high in sugar.

Normal results
Ideally TPN will provide all the nutrients in the
correct quantity to allow the body to function
normally.
3735

Total parenteral nutrition

Precautions

Tourette syndrome

Abnormal results
Fluid and electrolyte imbalances may occur that
can lead to major organ failure.
OTHER

Al-Jurf, Adel S. and Karen Dillon ‘‘Indications for Total
Parenteral Nutrition (TPN).’’ University of Iowa Virtual
Hospital. March 2003 [cited 16 February 2005].
<http://www.vh.org/adult/provider/surgery/
totalparenteralnutrition>.
‘‘Drug Information: Total Parenteral Nutrition.’’ Medline
Plus Medical Encyclopedia. 1 April 2003 [cited 16
February 2005]. <http://www.nlm.nih.gov/
medlineplus/druginfo/medmaster/a601166.html>.
‘‘Nutritional Support: Total Parenteral Nutrition.’’
The Merck Manual. Eds. Mark H. Beers and
Robert Berkow. 1995-2005 [cited 27 February 2005].
<http://www.merck.com/mrkshared/mmanual/
section1/chapter1/1c.jsp>.

Tish Davidson, A.M.

Total protein test see Protein components
test

Tourette syndrome
Definition
Tourette syndrome (TS) is an inherited disorder
of the nervous system, characterized by a variable
expression of unwanted movements and noises
(tics).

Description
The first references in the literature to what might
today be classified as Tourette syndrome largely
describe individuals who were wrongly believed to be
possessed by the devil. In 1885 Gilles de la Tourette, a
French neurologist, provided the first formal description of this syndrome, which he described as an inherited neurological condition characterized by motor
and vocal tics.
Although vocal and motor tics are the hallmark of
Tourette syndrome, such other symptoms as the
expression of socially inappropriate comments or
behaviors, obsessive compulsive disorder, attention
deficit disorder, self-injuring behavior, depression,
and anxiety also appear to be associated with
Tourette syndrome. Most research suggests that
3736

Tourette syndrome is an autosomal dominant disorder, although a gene responsible for Tourette syndrome has not yet been discovered.
Tourette syndrome is found in all populations and
all ethnic groups, but is three to four times more
common in males than females and is more common
in children than adults. The exact frequency of
Tourette syndrome is unknown, but estimates range
from 0.05% to 3%.

Causes and symptoms
The cause of Tourette syndrome is unknown,
although some studies suggest that the tics in
Tourette syndrome are caused by an increased amount
of a neurotransmitter called dopamine. A neurotransmitter is a chemical found in the brain that helps to
transmit information from one brain cell to another.
Other studies suggest that the defect in Tourette syndrome involves another neurotransmitter called serotonin; or involves other chemicals required for normal
functioning of the brain.
Most studies suggest that Tourette syndrome is an
autosomal dominant disorder with decreased penetrance, although this hypothesis has not been proven
and may not be true in all families. An autosomal
dominant disorder results from a change in one copy
of a pair of genes. Individuals with an autosomal
dominant disorder have a 50% chance of passing on
the changed gene to their children. Decreased penetrance means that not all people who inherit the changed gene will develop symptoms. There is some
evidence that females who inherit the Tourette syndrome gene have a 70% chance of exhibiting symptoms and males have a 99% chance of having
symptoms. It has been suggested that other genetic
and environmental factors may play a role in the
development of symptoms in people who inherit
the changed gene, but none have been discovered.
Some researchers believe that Tourette syndrome
has different causes in different individuals or is
caused by changes in more than one gene, although
these theories are less substantiated. Further
research is needed to establish the cause of Tourette
syndrome.
Motor and vocal tics
The principal symptoms of Tourette syndrome
include simple and complex motor and vocal tics.
Simple motor tics are characterized by brief muscle
contractions of one or more limited muscle groups. An
eye twitch is an example of a simple motor tic.
GALE ENCYCLOPEDIA OF MEDICINE

Vocal tics are actually manifestations of motor tics
that involve the muscles required for vocalization.
Simple vocal tics include stuttering, stammering, abnormal emphasis of part of a word or phrase, and inarticulate noises such as throat clearing, grunts, and
high-pitched sounds. Complex vocal tics typically
involve the involuntary expression of words. Perhaps
the most striking example of this is coprolalia, the involuntary expression of obscene words or phrases, which
occurs in fewer than one-third of people with Tourette
syndrome. The involuntary echoing of the last word,
phrase, sentence or sound vocalized by oneself (phalilalia) or of another person or sound in the environment
(echolalia) are also classified as complex tics.
The type, frequency, and severity of tics exhibited
varies tremendously between individuals with
Tourette syndrome. Tourette syndrome has a variable
age of onset and tics can start anytime between infancy
and age 18. Initial symptoms usually occur before the
early teens; the mean age of onset for both males and
females is approximately seven years of age. Most
individuals with symptoms initially experience simple
muscle tics involving the eyes and the head. These
symptoms can progress to tics involving the upper
torso, neck, arms, hands, and occasionally the legs
and feet. Complex motor tics are usually the latestonset muscle tics. Vocal tics usually have a later onset
then motor tics. In some rare cases, people with
Tourette syndrome suddenly present with multiple,
severe, or bizarre symptoms.
Not only is there extreme variability in clinical
symptoms between individuals with Tourette syndrome, but individuals commonly experience a variability in type, frequency, and severity of symptoms
over the course of their lifetime. Adolescents with
Tourette syndrome often experience unpredictable
and variable symptoms, which may be related to fluctuating hormone levels and decreased compliance in
taking medications. Adults often experience a
decrease in symptoms or a complete end to symptoms.
A number of factors appear to affect the severity
and frequency of tics. Stress appears to increase the
frequency and severity of tics, while concentration on
another part of the body that is not involved in a tic
GALE ENCYCLOPEDIA OF MEDICINE

can result in the temporary alleviation of symptoms.
Relaxation, following attempts to suppress the
occurrence of tics, may result in an increased frequency of tics. An increased frequency and severity
of tics can also result from exposure to such drugs
as steroids, cocaine, amphetamines, and caffeine.
Hormonal changes such as those that occur prior to
the menstrual cycle can also increase the severity of
symptoms.
Other associated symptoms
People with Tourette syndrome are more likely to
exhibit non-obscene, socially inappropriate behaviors
such as expressing insulting or socially unacceptable
comments or socially unacceptable actions. It is not
known whether these symptoms stem from a more
general dysfunction of impulse control that might be
part of Tourette syndrome.
Tourette syndrome appears to also be associated
with attention deficit disorder (ADD). ADD is a disorder characterized by a short attention span and
impulsivity, and in some cases hyperactivity.
Researchers have found that 21–90% of individuals
with Tourette syndrome also exhibit symptoms of
ADD, whereas 2–15% of the general population exhibit symptoms of ADD.
People with Tourette syndrome are also at higher
risk for having symptoms of obsessive-compulsive disorder (OCD). OCD is a disorder characterized by
persistent, intrusive, and senseless thoughts (obsessions) or compulsions to perform repetitive behaviors
that interfere with normal functioning. A person with
OCD, for example, may be obsessed with germs and
may counteract this obsession with continual hand
washing. Symptoms of OCD are present in 1.9–3%
of the general population, whereas 28–50% of people
with Tourette syndrome have symptoms of OCD.
Self-injurious behavior (SIB) is also seen more
frequently in those with Tourette syndrome.
Approximately 34–53% of individuals with Tourette
syndrome exhibit some form of self-injuring behavior.
The SIB is often related to OCD but can also occur in
those with Tourette syndrome who do not have OCD.
Symptoms of anxiety and depression are also
found more commonly in people with Tourette syndrome. It is not clear, however, whether these symptoms are symptoms of Tourette syndrome or occur as
a result of having to deal with the symptoms of moderate to severe Tourette syndrome.
People with Tourette syndrome may also be at
increased risk for having learning disabilities and
3737

Tourette syndrome

Complex motor tics tend to appear more complicated
and purposeful than simple tics, and involve coordinated contractions of several muscle groups. Some
examples of complex motor tics include the act of
hitting oneself and jumping. Copropraxia, the involuntary display of unacceptable/obscene gestures; and
echopraxia, the imitation of the movement of another
individual, are other examples of complex motor tics.

Tourette syndrome

personality disorders; and may be more predisposed to
such behaviors as aggression, antisocial behaviors,
severe temper outbursts, and inappropriate sexual
behavior. Further controlled studies need to be performed, however, to ascertain whether these behaviors
are symptoms of Tourette syndrome.

Diagnosis
Tourette syndrome cannot be diagnosed through
a blood test. The diagnosis is made through observation and interview of the patient and discussions with
other family members. The diagnosis, of Tourette syndrome is complicated by a variety of factors. The
extreme range of symptoms of this disorder makes it
difficult to differentiate Tourette syndrome from other
disorders with similar symptoms. Diagnosis is further
complicated by the fact that some tics appear to be
within the range of normal behavior. For example an
individual who only exhibits such tics as throat clearing and sniffing may be misdiagnosed with a medical
problem such as allergies. In addition, such bizarre
and complex tics as coprolalia may be mistaken for
psychotic or ‘‘bad’’ behavior. Diagnosis is also confounded by individuals who attempt to control tics in
public and in front of health care professionals and
deny the existence of symptoms. Although there is
disagreement over what criteria should be used to
diagnosis Tourette syndrome, one aid in the diagnosis
is the DSMMD (DSM-IV). The DSM-IV outlines
suggested diagnostic criteria for a variety of conditions including Tourette syndrome.
DSM-IV criteria


presence of both motor and vocal tics at some time
during the course of the illness



the occurrence of multiple tics nearly every day
through a period of more than one year, without a
remission of tics for a period of greater than three
consecutive months



the symptoms cause distress or impairment in
functioning



age of onset of prior to 18 years of age



the symptoms are not due to medications or drugs
and are not related to another medical condition

Some physicians critique the DSM-IV criteria,
arguing that they do not include the full range of
behaviors and symptoms seen in Tourette syndrome.
Others criticize the criteria since they limit the diagnosis to those who experience a significant impairment, which may not be true for individuals with
milder symptoms. For this reason many physicians
3738

use their clinical judgment as well as the DSM-IV
criteria as a guide to diagnosing Tourette syndrome.

Treatment
There is no cure for Tourette syndrome. Treatment
involves the control of symptoms through educational
and psychological interventions and/or medications.
The treatment and management of Tourette syndrome
varies from patient to patient and should focus on the
alleviation of the symptoms that are most bothersome
to the patient or that cause the most interference with
daily functioning.
Psychological and educational interventions
Psychological treatments such as counseling are
not generally useful for the treatment of tics but can
be beneficial in the treatment of such associated symptoms as obsessive-compulsive behavior and attention
deficit disorder. Counseling may also help individuals
to cope better with the symptoms of this disorder and to
have more positive social interactions. Psychological
interventions may also help people cope better with
stressors that can normally be triggers for tics and
negative behaviors. Relaxation therapies may, however, increase the occurrence of tics. The education of
family members, teachers, and peers about Tourette
syndrome can be helpful and may help to foster acceptance and prevent social isolation.
Medications
Many people with mild symptoms of Tourette
syndrome never require medications. Those with
severe symptoms may require medications for all or
part of their lifetime. The most effective treatment of
tics associated with Tourette syndrome involves the
use of drugs such as haloperidol, pimozide, sulpiride,
and tiapride, which decrease the amount of dopamine
in the body. Unfortunately, the incidence of side
effects, even at low dosages, is quite high. The shortterm side effects can include sedation, dysphoria,
weight gain, movement abnormalities, depression,
and poor school performance. Long-term side effects
can include phobias, memory difficulties, and personality changes. These drugs are therefore better candidates for short-term rather than long-term therapy.
Tourette syndrome can also be treated with such
other drugs as clonidine, clonazepam, and risperidone,
but the efficacy of these treatments is unknown. In
many cases, treatment of such as associated conditions
such as ADD and OCD is often more of a concern
than the tics themselves. Clonidine used in
GALE ENCYCLOPEDIA OF MEDICINE

Attention deficit disorder (ADD)—Disorder characterized by a short attention span, impulsivity, and
in some cases hyperactivity.
Autosomal dominant—A pattern of genetic inheritance in which only one abnormal gene is needed to
display the trait or disease.
Coprolalia—The involuntary expression of obscene
words or phrases.
Copropraxia—The involuntary display of unacceptable/obscene gestures.
Decreased penetrance—Individuals who inherit a
changed disease gene but do not develop
symptoms.
Dysphoria—Feelings of anxiety, restlessness, and
dissatisfaction.
Echolalia—Involuntary echoing of the last word,
phrase, or sentence spoken by someone else or
sound in the environment.

The prognosis for Tourette syndrome in individuals without associated psychological conditions
is often quite good, and only approximately 10% of
Tourette syndrome individuals experience severe
tic symptoms. Approximately 30% of people with
Tourette syndrome will experience a decrease in the
frequency and severity of tics, and another 30–40%
will experience a complete end of symptoms by late
adolescence. The other 30–40% will continue to exhibit moderate to severe symptoms in adulthood. There
does not appear to be a definite correlation between
the type, frequency, and severity of symptoms and the
eventual prognosis. Patients with severe tics may
experience social difficulties and may isolate themselves from others in fear of shocking and embarrassing them. People with Tourette syndrome who have
such other symptoms as obsessive compulsive disorder, attention deficit disorder, and self-injurious
behavior usually have a poorer prognosis.
Resources

Echopraxia—The imitation of the movement of
another individual.
Neurotransmitter—Chemical in the brain that
transmits information from one nerve cell to
another.

BOOKS

Obsessive compulsive disorder (OCD)—Disorder
characterized by persistent, intrusive, and senseless
thoughts (obsessions) or compulsions to perform
repetitive behaviors that interfere with normal
functioning.

PERIODICALS

Phalilalia—Involuntary echoing of the last word,
phrase, sentence, or sound vocalized by oneself.

National Institute of Neurological Disorders and Stroke. 31
Center Drive, MSC 2540, Bldg. 31, Room 8806,
Bethesda, MD 20814. (301) 496-5751 or (800) 352-9424.
<http://www.ninds.nih.gov>.
National Tourette Syndrome Association, Inc. 42-40 Bell
Blvd., Bayside, NY 11361-2820. (718) 224-2999. Fax:
(718) 279-9596. tourette@ix.netcom.com.
Tourette Syndrome Foundation of Canada. 194 Jarvis
Street, #206, Toronto, ONT M5B 2B7. Canada (800)
361-3120. tsfc.org@sympatico.ca. <http://
www.tourette.ca>.

Tic—Brief and intermittent involuntary movement
or sound.

conjunction with such stimulants as Ritalin may be
useful for treating people with Tourette syndrome
who also have symptoms of ADD. Stimulants should
be used with caution in individuals with Tourette syndrome since they can sometimes increase the frequency and severity of tics. OCD symptoms in those
with Tourette syndrome are often treated with such
drugs as Prozac, Luvox, Paxil, and Zoloft.
In many cases the treatment of Tourette syndrome
with medications can be discontinued after adolescence. Trials should be performed through the gradual
tapering off of medications and should always be done
under a doctor’s supervision.
GALE ENCYCLOPEDIA OF MEDICINE

Leckman, James, and Donald Cohen. Tourette’s
Syndrome:Tics, Obsessions, Compulsions: Development,
Psychopathology and Clinical Care. NewYork: John
Wiley & Sons, 1999.
Robertson, Mary. ‘‘Tourette Syndrome, Associated
Conditionsand the Complexities of Treatment.’’ Brain
123 (2000): 425–462.
ORGANIZATIONS

OTHER

‘‘About Tourette Syndrome.’’ Tourette Help. <http://
www.tourettehelp.com/pages/patient/about.html>.
‘‘Tourette’s Disorder.’’ Internet Mental Health. <http://
www.mentalhealth.com/fr20.html>.

Lisa Maria Andres, MS, CGC

Toxic encephalopathy see Delirium
3739

Tourette syndrome

Prognosis

KEY TERMS

Toxic epidermal necrolysis

KEY TERMS

Toxic epidermal necrolysis
Definition
Toxic epidermal necrolysis is a rare condition that
causes large portions of the epidermis, the skin’s outermost layer, to detach from the layers of skin below.
A reaction to a medication is the primary cause.

Description
Toxic epidermal necrolysis (TEN) begins with
fever, cough, and other nonspecific symptoms, and is
soon followed by purplish, bloody-looking lesions on
the skin and mucous membranes. These early lesions,
typically found on the head, neck, and upper chest,
soon merge and blister. Sheets of epidermis then begin
to detach from the skin layers below. In time, the
entire surface of the skin may be involved, with
detachment of 100% of the epidermis.

Causes and symptoms
The main cause of TEN is a severe drug reaction.
Some investigators believe there may be additional
infectious causes. A severe reaction in transplant
patients, called graft-vs.-host disease, can also produce
TEN. One study reported more than 100 different
drugs as causes of TEN. The drugs most commonly
implicated, however, include antibacterial sulfonamides
such as sulfadiazine, antibiotics such as aminopenicillins and cephalosporins, and anticonvulsants like phenytoin. TEN is extremely rare. Researchers estimate
that there are 0.2 cases per million users of aminopenicillins and 4.5 cases per million users of sulfonamides.
Exactly what leads to detachment of the epidermis
remains unclear. People with TEN seem to have difficulty metabolizing the offending drug. Some researchers suggest that certain substances that should be
cleared from the body instead get deposited on the
outer shell of the epidermis, causing an immune
response that leads the body to ‘‘reject’’ the skin.

Diagnosis
Diagnosis is made primarily on the appearance and
spread of the skin lesions, and on a history that includes
introduction of a new medication within the previous
one to three weeks. A biopsy of the early lesions will
confirm the diagnosis. Physicians will consider other
potential diseases that cause similar symptoms before
reaching a diagnosis of TEN. One is erythema multiforme, a recurrent skin disorder that produces lesions

3740

Epidermis—The outermost layer of the skin.
Erythema multiforme—A recurrent skin disorder
that produces lesions similar in appearance to
TEN, but is not caused by a drug reaction and
does not lead to sheet-like shedding of the skin.
Staphylococcal scalded skin syndrome—A disease
caused by Staphylococcus aureus, in which large
sheets of skin may peel away from the body. It most
often affects infants, young children, and people
with weakened immune systems.
Stevens-Johnson syndrome—A drug-induced skin
disease that some experts believe is really a milder
form of TEN.

similar in appearance to TEN. However, this disorder is
not caused by a drug reaction and does not lead to
sheet-like shedding of the skin. Another disease,
Stevens-Johnson syndrome, is a drug-induced skin disease that some experts believe is really a milder form of
TEN. Staphylococcal scalded skin syndrome (SSSS) also
looks like TEN, but it is caused by a staphylococcal
infection. Unlike TEN, which occurs rarely in children,
SSSS primarily affects infants, young children, and
adults with weakened immune systems.

Treatment
There is no specific treatment for TEN. Patients are
typically treated in an intensive care unit or in a burn unit
and receive treatment similar to that given to patients
with major burns. With the loss of skin, severe dehydration is a major risk, so health care workers will attempt to
replace fluids intravenously. Nutritional supplementation from a tube routed through the nose to the stomach
may also be contemplated to promote the healing of the
skin. Infection is a major risk, so some physicians ‘‘paint’’
the open lesions with topical antiseptics. Others use skin
grafts taken from cadavers or cultured skin substitutes to
cover large open areas until healing can occur. Some
investigators believe system corticosteroids are useful in
the treatment of TEN. But since these medications have
also been implicated as a cause in some cases of TEN and
are known to supress the immune system, their use
should be considered carefully.

Prognosis
About 25-30% of patients with TEN die. Elderly
patients, those with extensive skin lesions, and those
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
There is no prevention for TEN. No reliable test can
indicate that a specific drug may cause TEN in a specific
patient. Some researchers believe skin tests of potentially
offending drugs may prove useful in the future.
Resources
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham Road,
P.O. Box 4014, Schaumburg, IL 60168-4014. (847) 3300230.Fax: (847) 330-0050. <http://www.aad.org>.

Richard H. Camer

Toxic shock syndrome
Definition
Toxic shock syndrome (TSS) is an uncommon, but
potentially serious, illness that occurs when poisonous
substances (toxins) produced by certain bacteria enter
the bloodstream. The toxins cause a type of blood
poisoning caused by staphylococcal, or less commonly
streptococcal, infections in the lungs, throat, skin or
bone, or from injuries. Women using super-absorbent
tampons during menstruation were found to be most
likely to get toxic shock syndrome.

Description
TSS first came to the attention of the public in the
1970s. Shortly after the introduction of a superabsorbent tampon, young women across the United
States experienced an epidemic of serious but unexplained symptoms. Thousands went to emergency
rooms with high fever, vomiting, peeling skin, low
blood pressure, diarrhea, and a rash resembling sunburn. The only thing they had in common was that
they all were menstruating at the time they felt sick,
and all were using tampons, especially super-absorbent products.
At its height, the epidemic affected 15,000 people
in the United States each year between 1980 and 1984;
15% of the women died. Since the offending products
were taken off the market, the number of TSS cases
GALE ENCYCLOPEDIA OF MEDICINE

has declined sharply. As of 1998, only about 5,000
cases are diagnosed annually in the United States,
5% of which are fatal. The decline most likely is due
to tampon manufacturers discontinuing the use of
some synthetic materials, and the removal from the
market of the brand of tampon associated with most
cases of TSS. Today, most of these products are made
with rayon and cotton.
In spite of TSS’ association with menstruating
women, the disease can affect anyone of either sex or
any age or race. The infection may occur in children,
men, and non-menstruating women who are weakened from surgery, injury, or disease, and who cannot
fight off a staphylococcal infection. New mothers also
are at higher risk for TSS.
Most cases reported in the recent past, however,
still involve menstruating women under age 30. TSS
still occurs in about 17 out of every 100,000 menstruating girls and women each year; more than half of
these cases are related to tampons. Between five and
10% of patients with TSS die.
Streptococcal toxic shock syndrome (STSS)
A new type of toxic shock syndrome is caused by a
different bacteria, called Group A streptococcus. This
form of TSS is called streptococcal toxic shock syndrome, or STSS. Officially recognized in 1987, STSS is
related to the strain of streptococcus nicknamed the
‘‘flesh-eating bacterium.’’ STSS affects only one or
two out of every 100,000 Americans. It almost never
follows a simple strep throat infection.

Causes and symptoms
Transmission
TSS is caused by a strain of Staphylococcus aureus
found in the nose, mouth, and occasionally the vagina.
The bacteria produce a characteristic toxin. In large
enough quantities, the toxin can enter the bloodstream, causing a potentially fatal infection.
While experts know the name of the bacterium, more than 10 years after the 1980s epidemic
scientists still do not fully understand the link
between TSS and tampons. Most medical researchers today suspect that the absorbent tampons
introduce oxygen into the vagina, which is normally an oxygen-free area of the body. Oxygen
triggers bacterial growth, and the more absorbent
the tampon, the more bacteria it can harbor. Some
experts believe that the reason TSS is linked to
tampons in particular is that bacteria can contaminate and multiply in a tampon. If left in place
3741

Toxic shock syndrome

with AIDS have the worst prognosis. Widespread systemic infection (sepsis) is the primary cause of death.
Survivors, however, will be completely healed in three
to four weeks.

Toxic shock syndrome

for a long time–as a woman could do with a
super-absorbent product–the bacteria have a better
chance of multiplying and producing a large
amount of toxin. It also is possible that the tampons or the chemicals they contain may irritate the
vaginal lining, enabling the toxin to enter the
bloodstream.
These types of bacteria normally are present either
on hands or in the vagina, and it takes an amount
of bacteria only the size of a grain of sand to start
an infection. Of the 15% of women who carry
Staphylococcus aureus, only about 5% have the strain
that produces the TSS toxin.
Symptoms
TSS. TSS begins suddenly, with a high fever of
1028F (38.98C) or above, vomiting and watery diarrhea, headache, and sunburn-like rash, together with a
sore throat and body aches. Blood pressure may plummet a day or two after the first symptoms appear.
When the blood pressure drops, a woman may become
disoriented or go into shock. Her kidneys may fail.
After these developments, the skin on her hands and
feet may peel.
STSS. STSS can occur after a streptococcal infection in the body, usually from an infected wound or
even chickenpox. Within 48 hours, the patient’s blood
pressure drops. There also is fever, dizziness, breathing
problems, and a weak, rapid pulse. The area around
the wound may swell, the liver and kidneys can fail,
and bleeding problems may occur.

Diagnosis
Any woman who is wearing a tampon and begins
to experience the symptoms of toxic shock syndrome
should remove the tampon right away and seek medical care.
The doctor will probably examine the vagina
for signs of inflammation and rule out common sexually transmitted diseases with similar symptoms. A
variety of blood tests, tests of vaginal secretions,
and a physical examination are needed to identify
this condition.

Treatment
TSS
In a menstruating woman, the vagina first is
cleansed with an antiseptic solution to eliminate
some of the bacteria that produce the toxin. TSS is
3742

KEY TERMS
Shock—A condition in which the amount of blood
circulating in the body is inadequate to meet the
body’s needs. Shock can be caused by certain diseases, serious injury, or blood loss.
Staphylococcus—A genus of bacteria that is
commonly found on human skin and mucous
membranes.
Streptococcus—A genus of sphere-shaped bacteria that can cause a wide variety of infections.
Toxin—A poisonous protein that is produced by
some bacteria. A toxin is less complex than a
poison.

treated with antibiotics, together with other drugs and
fluids to lower fever and control blood pressure.
STSS
Antibiotics are used to treat STSS. Surgery may
be needed to remove dead skin and muscle. Research
continues on new therapy options to help improve
treatment of STSS, including intravenous therapy
with immunoglobulin. The therapy doesn’t replace
use of antibiotics but works along with it.

Prognosis
TSS lasts as long as three weeks, and has a tendency to recur. About a third of the women who are
treated for TSS have it again within six months. In
addition, TSS can affect the liver, kidneys, lungs, and
other organs, depending on the severity of the infection. Untreated toxic shock syndrome can be fatal. A
2003 report noted that a quick diagnosis of TSS is
critical to avoiding serious complications and death.

Prevention
TSS
Women who wear tampons should change them
often and use different brands and types of pads and
tampons. If a woman really prefers tampons, experts
recommend using the lowest possible absorbency product made of cotton and rayon, and wearing it only
during the day. In the past, it was difficult to compare
absorbency rates for different products. Today, the Food
and Drug Administration (FDA) requires standardized
absorbency measurements on all tampon boxes. Above
GALE ENCYCLOPEDIA OF MEDICINE

Anyone who has had TSS even once should not
use tampons again.
STSS
Doctors still are not sure how people can avoid
STSS, but they advise patients to clean and bandage
open wounds immediately. Anyone with a red, swollen,
or tender wound, or a sudden fever should seek medical care.
Resources
PERIODICALS

‘‘A Quick Diagnosis of Toxic Shock Syndrome Is Critical for
Avoiding Mortality.’’ Health & Medicine Week
December 1, 2003: 616.
‘‘Toxic Shock Syndrome May Be Treatable with IVIG
Therapy.’’ Blood Weekly October 2, 2003: 64.
OTHER

Kids Health Page. <http://KidsHealth.org>.

Carol A. Turkington
Teresa G. Odle

Toxocariasis see Roundworm infections
Toxoplasma gondii infection see
Toxoplasmosis

Toxoplasmosis
Definition
Toxoplasmosis is an infectious disease caused by
the one-celled protozoan parasite Toxoplasma gondii.
Although most individuals do not experience any
symptoms, the disease can be very serious, and even
fatal, in individuals with weakened immune systems.

Description
Toxoplasmosis is caused by a one-celled protozoan parasite known as Toxoplasm a gondii. Cats,
the primary carriers of the organism, become infected
by eating rodents and birds infected with the organism. Once ingested, the organism reproduces in the
intestines of cats, producing millions of eggs known
as oocysts, which are excreted in cat feces daily for
approximately two weeks. In the United States, it is
estimated that approximately 30% of cats have been
GALE ENCYCLOPEDIA OF MEDICINE

infected by T. gondii. Oocysts are not capable of producing infection until approximately 24 hours after
being excreted, but they remain infective in water or
moist soil for approximately one year. When cattle,
sheep, or other livestock forage through areas with
contaminated cat feces, these animals become carriers
of the disease. Fruits and vegetables can also become
contaminated when irrigated with untreated water
that has been contaminated with cat feces. In humans
and other animals, the organisms produce thickwalled, dormant structures called cysts in the muscle
and other tissues of the body.
Most humans contract toxoplasmosis by eating
cyst-contaminated raw or undercooked meat, vegetables, or milk products. Humans can also become
infected when they come into contact with the T. gondii
eggs while cleaning a cat’s litterbox, gardening, or playing in a sandbox, for instance. Once infected, an individual is immune to reinfection. The incubation period or
period between infection and the start of the disease
ranges from several days to months.
Anyone can be infected by T. gondii, but usually
only those individuals with weakened immune systems
(immunocompromised) develop symptoms of the disease. For them, toxoplasmosis can be severe, debilitating, and fatal. Immunocompromised individuals at
risk include those with AIDS, cancer, or other chronic
illnesses.
There is no person-to-person transmission, except
from an infected mother to her child in the womb.
Approximately six out of 1,000 women contract toxoplasmosis during pregnancy. Nearly half of these
maternal infections are passed on to the fetus.
Known as congenital toxoplasmosis, this form of the
disease is acquired at birth by approximately 3,300
infants in the United States every year. The risk of
fetal infection is estimated to be between one in 1,000
to one in 10,000. In children born with toxoplasmosis,
symptoms may be severe and quickly fatal, or may not
appear until several months or even years after birth.

Causes and symptoms
Healthy individuals do not usually display symptoms. When symptoms do occur, they are usually
mild, resembling infectious mononucleosis, and include
the following:


enlarged lymph nodes



muscle pains



intermittent fever



general sick feeling
3743

Toxoplasmosis

all, women should wash their hands before inserting a
tampon, and change the tampon every four to six hours.

Toxoplasmosis

The distinction is made between acquired toxoplasmosis, in which an individual becomes infected,
and neonatal congenital toxoplasmosis, in which a
fetus is born with the infection because the mother
became infected during pregnancy. If a fetus becomes
infected early in pregnancy, the disease can cause the
fetus to spontaneously abort, be stillborn. If full-term,
the infant may die in infancy or suffer from central
nervous system lesions. If the mother becomes infected
in the last three months of pregnancy, however, the
prognosis is good and the baby may not even display
any symptoms.
In adults, if the infection continues for an
extended period of time, chronic toxoplasmosis can
cause an inflammation of the eyes called retinochoroiditis, which can lead to blindness, severe yellowing
of the skin and whites of the eyes ( jaundice), easy
bruising, and convulsions.
Adults with weakened immune systems have a
high risk of developing cerebral toxoplasmosis,
including inflammation of the brain (encephalitis),
one-sided weakness or numbness, mood and personality changes, vision disturbances, muscle spasms, and
severe headaches. If untreated, cerebral toxoplasmosis
can lead to coma and death. This form of encephalitis
is the second most common AIDS-related nervous
system infection that takes advantage of a person’s
weakened immune system (opportunistic infection).

Diagnosis
A diagnosis of toxoplasmosis is made based on
clinical signs and supporting laboratory results,
including visualization of the protozoa in body tissue
or isolation in animals and blood tests. Laboratory
tests for toxoplasmosis are designed to detect
increased amounts of a protein or antibody produced
in response to infection with the toxoplasmosis organism. Antibody levels can be elevated for years, however, without active disease.

KEY TERMS
Cyst—The thick-walled dormant form of many
organisms.
Immunocompromised—A state in which the
immune system is suppressed or not functioning
properly.
Oocyst—The egg form of the toxoplasmosis
organism.
Protozoan—A single-celled, usually microscopic,
organism.

most physicians feel that treatment is justified.
Transmission of toxoplasmosis from the mother to
the fetus may be prevented if the mother takes the
antibiotic spiramycin. Later in a pregnancy, if the
fetus has contracted the disease, treatment with
the antibiotic pyrimethamine (Daraprim, Fansidar)
or sulfonamides may be effective. Babies born with
toxoplasmosis who show symptoms of the disease
may be treated with pyrimethamine, the sulfa drug
sulfadiazine (Microsulfon), and folinic acid (an active
form of folic acid).
AIDS patients who have not been infected may
be given a drug called TMP/SMX (Bactrim or Septra)
to prevent toxoplasmosis infection. To treat cases
of toxoplasmosis in immunocompromised AIDS
patients, a combination of pyrimethamine and a
sulfa-based drug, either sulfadiazine or clindamycin
(Cleocin), have been used together and can be effective
in treating this disease. Other antibiotic combinations
and dosing schedules are still being investigated.
Physicians have reported success in alleviating
symptoms by using trimethoprim-sulfamethoxazole
(Proloprim or Trimpex) or dapsone (DDS) plus pyrimethamine. These drugs can produce side effects,
such as allergic reaction, itching, rashes;, and nausea
and patients must be monitored closely.

Treatment
Most individuals who contract toxoplasmosis do
not require treatment because their immune systems
are able to control the disease. Symptoms are not
usually present. Mild symptoms may be relieved by
taking over-the-counter medications, such as acetaminophen (Tylenol) and ibuprofen (Motrin, Advil).
Sore throat lozenges and rest may also ease the
symptoms.
Although the treatment of women infected with
toxoplasmosis during pregnancy is controversial,
3744

Prognosis
The prognosis is poor when congenital toxoplasmosis is acquired during the first three months of pregnancy. Afflicted children die in infancy or suffer damage
to their central nervous systems that can result in physical and mental retardation. Infection later in pregnancy
usually results in only mild symptoms, if any. The prognosis for acquired toxoplasmosis in adults with strong
immune systems is excellent. The disease often disappears by itself after several weeks. However, the
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
There are no drugs that can eliminate T. gondii
cysts in animal or human tissues. Humans can reduce
their risks of developing toxoplasmosis by practicing
the following:


freezing (to 10.48F/–128C) and cooking foods to an
internal temperature of 1528F/678C will kill the cyst



practicing sanitary kitchen techniques, such as washing utensils and cutting boards that come into contact with raw meat



keeping pregnant women and children away from
household cats and cat litter



disposing of cat feces daily, because the oocysts do
not become infective until after 24 hours



helping cats to remain free of infection by feeding
them dry, canned, or boiled food and by discouraging hunting and scavenging



washing hands after outdoor activities involving soil
contact and wearing gloves when gardening

Resources
PERIODICALS

Rose, I. ‘‘Morphology and Diagnostics of Human
Toxoplasmosis.’’ General & Diagnostic Pathology 142
(June 1997): 257-70.

Maury M. Breecher, PhD

Toxoplasmosis, Other, Rubella,
Cytomegalovirus, Herpes simplex test see
TORCH test

Trabeculectomy
Definition
Trabeculectomy is a surgical procedure that
removes part of the trabeculum in the eye to relieve
pressure caused by glaucoma.
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
Glaucoma is a disease that injures the optic nerve,
causing progressive loss of vision. Presently, glaucoma is
a major cause of blindness in the United States If caught
early, glaucoma-related blindness is easily prevented.
However, since it does not produce symptoms until late
in its cycle, periodic tests for the disease are necessary.
Glaucoma is usually associated with an increase in
the pressure inside the eye. This increase occurs in front
of the iris in a fluid called the aqueous humor. Aqueous
humor is supposed to exit through tiny channels
between the iris and the cornea, in an area called the
trabeculum. When the trabeculum is blocked, pressure
from the build up of aqueous humor either increases
rapidly with considerable pain and redness, or, as in
most cases, the pressure builds slowly with no symptoms until much of the vision is lost. Trabeculectomy is
the last treatment employed for either type of glaucoma. It is used only after medications and laser trabeculoplasty (less invasive procedure that uses a laser to
open the blocked trabeculum) have failed to alleviate
the pressure.

Description
A trabeculectomy involves removing a tiny piece of
the eyeball right at the place where the cornea connects
to the sclera (the white part), and creating a flap to
allow fluid to escape the anterior chamber without
deflating the eye. Along with that tiny piece of cornea
and sclera comes a piece of the iris. The whole area is
called the trabeculum. Fluid can then flow out onto the
surface of the eye and be absorbed by the conjunctiva,
the transparent membrane that lines the sclera and the
eyelids. Sometimes, an additional piece is taken out of
the iris so that anterior chamber fluid can also flow
backward into the vitreous part of the eye. This procedure is called an iridectomy.

Preparation
The procedure and its benefits and possible complications are fully explained. Antiglaucoma drugs are
prescribed before surgery. Added pressure on the eye
caused from coughing or sneezing should be avoided.

Aftercare
Eye drops, and perhaps patching, will be
needed until the eye is healed. The pressure inside
the eye will still be monitored. Immediately following the procedure, the patient may experience
blurred vision.
3745

Trabeculectomy

prognosis for immuniodeficient patients is not as positive. These patients often relapse when treatment is
stopped. The disease can be fatal to all immunocompromised patients, especially AIDS patients, and particularly if not treated. As a result, immunocompromised
patients are typically placed on anti-toxoplasmosis
drugs for the rest of their lives.

Tracheoesophageal fistula

KEY TERMS
Cornea—Transparent film that covers the iris and
pupil.
Iris—Colored part of the eye, which is suspended
in aqueous humor and perforated by the pupil.
Sclera—White, outer coating of the eyeball.
Trabeculoplasty—Laser surgery that creates perforations in the trabeculum, to drain built up aqueous humor and relieve pressure.
Trabeculum—Tissue that is a drainage point for
aqueous humor in the eye.

and mucus is breathed into the lungs causing aspiration pneumonia and breathing problems.
Most tracheoesophageal fistulas are diagnosed
when a child is born. There are three types. In
85–90% of tracheoesophageal fistulas, the top part
of the esophagus ends in a blind sac, and the lower
part inserts into the trachea. In the second type, the
upper part of the esophagus is connected directly to
the trachea, while the lower part ends in a pouch. In a
rare type of fistula called an H type, both the esophagus and trachea are complete, but they are connected.
This is the most difficult type of tracheoesophageal
fistula to diagnose, because both eating and breathing
are possible.

Causes and symptoms

Risks
Infection and bleeding are risks of any surgery.
Scarring can cause the drainage to stop. A third of
patients with trabeculectomies will develop cataracts.
Resources
BOOKS

Vaughan, Daniel, editor. General Ophthalmology. 13th ed.
Stamford: Appleton & Lange, 1993.

Tracheoesophageal fistulas arise as a developmental abnormality. At birth, the infant has difficulty
swallowing. Eating produces severe coughing spells
that interfere with breathing. Aspiration pneumonia
can develop from fluid breathed into the lungs.
Small H type fistulas may go undiagnosed until
later in life. Symptoms of an H type fistula include
frequent pulmonary infections and bouts of abdominal bloating.

J. Ricker Polsdorfer, MD

Tracheoesophageal fistula
Definition
Tracheoesophageal fistula (TEF) is commonly a
birth defect, with the trachea connected to the esophagus. In most cases, the esophagus is discontinuous,
causing immediate feeding difficulties. TEFs may
develop in adult life, secondary to the invasion of
cancer in the area. In addition, TEFs may be deliberately constructed with surgery to aid talking in a
patient who has the larynx removed (a laryngectomy).

Description
The trachea, or windpipe, carries air to the lungs.
The esophagus carries food to the stomach.
Sometimes during development, these two tubes do
not separate completely, but remain connected by a
short passage. When this happens, air enters the gastrointestinal system, causing the bowels to distend,
3746

Diagnosis
Diagnosis that the esophagus is interrupted is
confirmed by the inability to insert a nasogastric suction tube into the stomach. The exact type and location of the fistula can be determined using a
radiopaque catheter, which allows pictures to be
taken of the esophagus. X rays may show air in the
bowels. Endoscopy often fails to located the fistula if it
is small.

Treatment
Babies with all but H type fistulas are unlikely to
survive without surgical separation and repair of the
trachea and the esophagus. Surgery cannot always be
performed immediately because of prematurity, the
presence of other birth defects, or complications
from aspiration pneumonia. It is usually done at a
hospital that has special facilities for treating seriously
ill newborns.
While awaiting surgery, the infant’s condition is
stabilized. Preoperative care concentrates on avoiding
aspiration pneumonia and includes:


elevating the head to avoid reflux and aspiration of
the stomach contents
GALE ENCYCLOPEDIA OF MEDICINE

Endoscopy—A procedure in which an instrument
containing a camera and a light source is
inserted into the gastrointestinal tract so that the
physician can visually inspect the gastrointestinal system.
Gastrostomy tube—Stomach tube for feeding.
Laryngectomy—Surgical removal of the larynx to
treat cancer.

Tracheotomy
Definition
A tracheotomy is a surgical procedure in which a
cut or opening is made in the windpipe (trachea). The
surgeon inserts a tube into the opening to bypass an
obstruction, allow air to get to the lungs, or remove
secretions. The term tracheostomy is sometimes used
interchangeably with tracheotomy. Strictly speaking,
however, tracheostomy usually refers to the opening
itself while a tracheotomy is the actual operation.

Purpose


using a suction catheter to continuously removed
mucus and saliva that could be inhaled



when necessary, placement of a gastrostomy tube



withholding feeding by mouth

When surgery is performed, the esophagus is
reconnected to make it continuous and separate from
the trachea. If the two ends of the esophagus are too
far apart to be reattached, a piece of tissue from the
large intestine is used to join the parts.

Prognosis

A tracheotomy is performed if enough air is not
getting to the lungs, if the person cannot breathe without help, or is having problems with mucus and other
secretions getting into the windpipe because of difficulty swallowing. There are many reasons why air
cannot get to the lungs. The patient’s windpipe may
be blocked by a swelling; by a severe injury to the neck,
nose or mouth; by a large foreign object; by paralysis
of the throat muscles; or by a tumor. The patient may
be in a coma, or need a ventilator to pump air into the
lungs for a long period of time.

Precautions

Infants who have tracheoesophageal fistula often
have other birth defects that affect their recovery. Even
when the esophagus is successfully separated and reattached, many infants have difficulty swallowing,
because the contractility of the esophagus is impaired.
Infants may also have problems with gastroesophageal reflux, in which the acidic contents of the stomach
back up into the bottom of the esophagus and cause
ulcers and scarring.

Prevention
Tracheoesophageal fistulas are not preventable
birth defects.
Resources

Doctors perform emergency tracheotomies as
last-resort procedures. They are done only if the
patient’s windpipe is obstructed and the situation is
life-threatening.

Description
Emergency tracheotomy
There are two different procedures that are called
tracheotomies. The first is done only in emergency
situations and can be performed quite rapidly. The
emergency room physician or surgeon makes a cut in
a thin part of the voice box (larynx) called the cricothyroid membrane. A tube is inserted and connected
to an oxygen bag. This emergency procedure is sometimes called a cricothyroidotomy.

BOOKS

Berktow, Robert, editor. ‘‘Gastrointestinal Defects.’’ In The
Merck Manual ofDiagnosis and Therapy. Rahway, NJ:
Merck Research Laboratories, 2004.

Tish Davidson, A.M.

Tracheostomy see Tracheotomy
GALE ENCYCLOPEDIA OF MEDICINE

Nonemergency tracheotomy
The second type of tracheotomy takes more time
and is usually done in an operating room. The surgeon first makes a cut (incision) in the skin of the neck
that lies over the trachea. This incision is in the lower
part of the neck between the Adam’s apple and top of
the breastbone. The neck muscles are separated and
3747

Tracheotomy

KEY TERMS

Tracheotomy

the thyroid gland, which overlies the trachea, is
usually cut down the middle. The surgeon identifies
the rings of cartilage that make up the trachea and
cuts into the tough walls. A metal or plastic tube,
called a tracheotomy tube, is inserted through the
opening. This tube acts like a windpipe and allows
the person to breathe. Oxygen or a mechanical ventilator may be hooked up to the tube to bring oxygen to
the lungs. A dressing is placed around the opening.
Tape or stitches (sutures) are used to hold the tube in
place.
After a nonemergency tracheotomy, the patient
usually stays in the hospital for three to five days,
unless there is a complicating condition. It takes
about two weeks to recover fully from the surgery.

Preparation
Emergency tracheotomy
In the emergency tracheotomy, there is no time to
explain the procedure or the need for it to the patient.
The patient is placed on his or her back with face
upward (supine), with a rolled-up towel between the
shoulders. This positioning of the patient makes it
easier for the doctor to feel and see the structures in
the throat. A local anesthetic is injected across the
cricothyroid membrane.
Nonemergency tracheotomy
In a nonemergency tracheotomy, there is time for
the doctor to discuss the surgery with the patient, to
explain what will happen and why it is needed. The
patient is then put under general anesthesia. The neck
area and chest are then disinfected as preparation for
the operation, and surgical drapes are placed over the
area, setting up a sterile field.

It takes most patients several days to adjust to
breathing through the tracheotomy tube. At first, it
will be hard even to make sounds. If the tube allows
some air to escape and pass over the vocal cords, then
the patient may be able to speak by holding a finger
over the tube. A patient on a ventilator will not be able
to talk at all.
The tube will be removed if the tracheotomy is
temporary. Then the wound will heal quickly and only
a small scar may remain. If the tracheotomy is permanent, the hole stays open and, if it is no longer needed,
it will be surgically closed.
Home care
After the patient is discharged, he or she will need
help at home to manage the tracheotomy tube. Warm
compresses can be used to relieve pain at the incision site.
The patient is advised to keep the area dry. It is recommended that the patient wear a loose scarf over the
opening when going outside. He or she should also
avoid contact with water, food particles, and powdery
substances that could enter the opening and cause
serious breathing problems. The doctor may prescribe
pain medication and antibiotics to minimize the risk of
infections. If the tube is to be kept in place permanently,
the patient can be referred to a speech therapist in order
to learn to speak with the tube in place. The tracheotomy
tube may be replaced four to 10 days after surgery.
Patients are encouraged to go about most of their
normal activities once they leave the hospital.
Vigorous activity is restricted for about six weeks. If
the tracheotomy is permanent, further surgery may be
needed to widen the opening, which narrows with
time.

Risks
Immediate risks

Aftercare
Postoperative care
A chest x ray is often taken, especially in children,
to check whether the tube has become displaced or if
complications have occurred. The doctor may prescribe antibiotics to reduce the risk of infection. If the
patient can breathe on their own, the room is humidified; otherwise, if the tracheotomy tube is to remain in
place, the air entering the tube from a ventilator is
humidified. During the hospital stay, the patient and
his or her family members will learn how to care for
the tracheotomy tube, including suctioning and clearing it. Secretions are removed by passing a smaller
tube (catheter) into the tracheotomy tube.
3748

There are several short-term risks associated with
tracheotomies. Severe bleeding is one possible complication. The voice box or esophagus may be damaged
during surgery. Air may become trapped in the surrounding tissues or the lung may collapse. The tracheotomy tube can be blocked by blood clots, mucus,
or the pressure of the airway walls. Blockages can be
prevented by suctioning, humidifying the air, and
selecting the appropriate tracheotomy tube. Serious
infections are rare.
Long-term risks
Over time, other complications may develop following a tracheotomy. The windpipe itself may
GALE ENCYCLOPEDIA OF MEDICINE

Tracheotomy

Thyroid
isthmus

Retractor
Figure A

Figure B

Figure C

Larynx
Thyroid
isthmus
Subcutaneous
tissues
Trachea
Muscle
Sutures
Thyroid
Treacheotomy
tube inserted
Figure D

Figure E

Figure F

Tracheotomy is a surgical procedure in which an opening is made in the windpipe or trachea. As shown in the illustration above,
the physician or surgeon will follow these steps in performing this procedure: Figure A: A vertical incision is made through the
skin. Figure B: Another incision is made through the subcutaneous tissues and muscles of the neck. Figure C: The neck
muscles are separated using retractors. Figure D: The thyroid isthumus is either cut or retracted. Figure E: The surgeon
identifies the rings of cartilage that make up the trachea and cuts into the walls. Figure F: A metal or plastic tube is inserted
into the opening and sutures are used to hold the tube in place. (Illustration by Electronic Illustrators Group.)

become damaged for a number of reasons, including
pressure from the tube; bacteria that cause infections
and form scar tissue; or friction from a tube that
moves too much. Sometimes the opening does not
close on its own after the tube is removed. This risk
is higher in tracheotomies with tubes remaining in
place for 16 weeks or longer. In these cases, the
wound is surgically closed.
High-risk groups
The risks associated with tracheotomies are
higher in the following groups of patients:
GALE ENCYCLOPEDIA OF MEDICINE



children, especially newborns and infants



smokers



alcoholics



obese adults



persons over 60



persons with chronic diseases or respiratory
infections



persons taking muscle relaxants, sleeping medications, tranquilizers, or cortisone

The overall risk of death from a tracheotomy is
less than 5%.
3749

Trachoma

Description

KEY TERMS
Cartilage—A tough, fibrous connective tissue that
forms various parts of the body, including the trachea and larynx.
Cricothyroidotomy—An emergency tracheotomy
that consists of a cut through the cricothyroid membrane to open the patient’s airway as fast as possible.
Larynx—A structure made of cartilage and muscle
that connects the back of the throat with the trachea. The larynx contains the vocal cords.
Trachea—The tube that leads from the larynx or
voice box to two major air passages that bring
oxygen to each lung. The trachea is sometimes
called the windpipe.
Ventilator—A machine that helps patients to
breathe. It is sometimes called a respirator.

Normal results
Normal results include uncomplicated healing of
the incision and successful maintenance of long-term
tube placement.
Resources
OTHER

‘‘Answers to Common Otolaryngology Health Care
Questions.’’ Department of Otolaryngology–Head
and Neck Surgery Page. University of Washington
School of Medicine. <http://weber.u.washington.edu/
otoweb/trach.html>.
Sicard, Michael W. ‘‘Complications of Tracheotomy.’’ The
Bobby R. Alford Department of Otorhinolaryngology
and Communicative Sciences.
<http:www.bcm.tmc.edu/oto/grand/12194.html>.

Jeanine Barone, Physiologist

Trachoma
Definition
Trachoma, which is also called granular conjunctivitis or Egyptian ophthalmia, is a contagious, chronic
inflammation of the mucous membranes of the eyes,
caused by Chlamydia trachomatis. It is characterized by
swelling of the eyelids, sensitivity to light, and eventual
scarring of the conjunctivae and corneas of the eyes.
3750

Trachoma is a major cause of blindness in the
world. It is found in the Far East, as well as countries
with desert climates. In the United States, it is most
common among certain Native Americans and in
parts of Appalachia. The infection is highly contagious in its early stages. Blindness results from recurrent untreated infections.
The conjunctiva is the clear mucous membrane
that lines the inside of the eyelid and covers the white
part (sclera) of the eye. Conjunctivitis is an inflammation of the conjunctiva.

Causes and symptoms
Trachoma is caused by C. trachomatis, a parasitic
organism closely related to bacteria. It is transmitted
by insects, by hand-to-eye contact, or by the sharing of
infected handkerchiefs or towels. The incubation period is about a week.
The early symptoms of trachoma include the
development of follicles (small sacs) on the conjunctivae of the upper eyelids, pain, swollen eyelids, a discharge, tearing, and sensitivity to light. If the infection
is not treated, the follicles develop into large yellow or
gray pimples, and small blood vessels develop inside
the cornea. In most cases, both eyes are infected.
Repeated infections eventually lead to contraction
and turning-in of the eyelids, scarring of the corneas
and conjunctivae, eventual blockage of the tear ducts,
and blindness.

Diagnosis
Diagnosis is based on a combination of the
patient’s history (especially living or traveling in
areas with high rates of trachoma) and examination
of the eyes. The doctor will look for the presence of
follicles or scarring. He or she will take a small sample
of cells from the patient’s conjunctivae and examine
them, following a procedure called Giemsa staining, to
confirm the diagnosis.

Treatment
Treatment of early-stage trachoma consists of four
to six weeks of antibiotic treatment with tetracycline,
erythromycin, or sulfonamides. Antibiotics should be
given without waiting for laboratory test results.
Treatment may combine oral medication with antibiotic ointment applied directly to the eyes. A single-dose
treatment with azithromycin is an alternative method.
GALE ENCYCLOPEDIA OF MEDICINE

A close-up of a human eye with trachoma. Trachoma is
caused by Chlamydia trahomatis and commonly results in
blindness if left untreated. (Custom Medical Stock Photo.
Reproduced by permission.)



seek treatment immediately if a child shows signs of
eye infection, and minimize his or her contact with
other children



teach children to wash hands carefully before touching their eyes



protect children from flies or gnats that settle around
the eyes



if someone has trachoma (or any eye infection), do
not share towels, pillowcases, etc; Wash items well



if medications are prescribed, follow the doctor’s
instructions carefully

Resources
BOOKS

KEY TERMS
Conjunctivitis—Inflammation of the conjunctivae,
which are the mucous membranes covering the
white part of the eyeball (sclera) and lining the
inside of the eyelids.
Cornea—The transparent front part of the eye that
allows light to enter.

Riordan-Eva, Paul, et al. ‘‘Eye.’’ In Current
MedicalDiagnosis and Treatment, 1998, edited by
Stephen McPhee, et al., 37th ed. Stamford: Appleton &
Lange, 1997.

Rebecca J. Frey, PhD

Ophthalmia—Inflammation of the eye. Usually
severe and affecting the conjunctiva. Trachoma is
sometimes called Egyptian ophthalmia.

Traction
Definition

Tetracyclines should not be given to pregnant women
or children below the age of seven years.
Patients with complications from untreated or
repeated infections are treated surgically. Surgery
can be used for corneal transplantation or to correct
eyelid deformities.

Prognosis
The prognosis for full recovery is excellent if the
patient is treated promptly. If the infection has progressed to the stage of follicle development, prevention
of blindness depends on the severity of the follicles, the
presence of additional bacterial infections, and the
development of scarring.

Prevention
There are vaccines available that offer temporary
protection against trachoma, but there is no
GALE ENCYCLOPEDIA OF MEDICINE

Traction is the use of a pulling force to treat
muscle and skeleton disorders.

Purpose
Traction is usually applied to the arms and legs,
the neck, the backbone, or the pelvis. It is used to treat
fractures, dislocations, and long-duration muscle
spasms, and to prevent or correct deformities.
Traction can either be short-term, as at an accident
scene, or long-term, when it is used in a hospital
setting.
Traction serves several purposes:


it aligns the ends of a fracture by pulling the limb into
a straight position



it ends muscle spasm



it relieves pain



it takes the pressure off the bone ends by relaxing the
muscle
3751

Traction

permanent immunization. Prevention depends upon
good hygiene and public health measures:

Traction

There are two main types of traction: skin traction
and skeletal traction. Within these types, many
specialized forms of traction have been developed to
address problems in particular parts of the body. The
application of traction is an exacting technique that
requires training and experience, since incorrectly
applied traction can cause harm.
Positioning the extremity so that the angle of pull
brings the ends of the fracture together is essential.
Elaborate methods of weights, counterweights, and
pulleys have been developed to provide the appropriate force while keeping the bones aligned and preventing muscle spasm. The patient’s age, weight, and
medical condition are all taken into account when
deciding on the type and degree of traction.

Precautions
People who are suffering from skin disorders or
who are allergic to tape should not undergo
skin traction, because the application of traction will
aggravate their condition. Likewise, circulatory
disorders or varicose veins can be aggravated by skin
traction. People with an inflammation of the bone
(osteomyelitis) should not undergo skeletal traction.

fractures. The purpose of this traction is to stabilize
the knee and reduce muscle spasm.
Skeletal traction
Skeletal traction is performed when more pulling
force is needed than can be withstood by skin traction;
or when the part of the body needing traction is positioned so that skin traction is impossible. Skeletal
traction uses weights of 25-40 pounds.
Skeletal traction requires the placement of tongs,
pins, or screws into the bone so that the weight is
applied directly to the bone. This is an invasive procedure that is done in an operating room under general,
regional, or local anesthesia.
Correct placement of the pins is essential to the
success of the traction. The pin can be kept in place
several months, and must be kept clean to prevent
infection. Once the hardware is in place, pulleys and
weights are attached to wires to provide the proper
pull and alignment on the affected part.
Specialized forms of skeletal traction include cervical traction used for fractures of the neck vertebrae;
overhead arm traction used for certain types of upper
arm fractures; and tibia pin traction used for some
fractures of the femur, hip, or pelvis.

Description
Skin traction
Skin traction uses five-to seven-pound weights
attached to the skin to indirectly apply the necessary
pulling force on the bone. If traction is temporary, or if
only a light or discontinuous force is needed, then skin
traction is the preferred treatment. Because the procedure is not invasive, it is usually performed in a hospital bed.
Weights are attached either through adhesive or
nonadhesive tape, or with straps, boots, or cuffs. Care
must be taken to keep the straps or tape loose enough
to prevent swelling and allow good circulation to the
part of the limb beyond the spot where the traction is
applied. The amount of weight that can be applied
through skin traction is limited because excessive
weight will irritate the skin and cause it to slough off.
Specialized forms of skin traction have been
developed to address specific problems. Dunlop’s
traction is used on children with certain fractures of
the upper arm, when the arm must be kept in a flexed
position to prevent problems with the circulation and
nerves around the elbow. Pelvic traction is applied to
the lower spine, with a belt around the waist. Buck’s
skin traction is used to treat knee injuries other than
3752

Preparation
X rays are done prior to the application of both
forms of traction, and may be repeated during treatment to assure that the affected parts are staying in
alignment and healing properly. Since the insertion of
the anchoring devices in skeletal traction is a surgical
procedure, standard preoperative blood and urine
testing are done, and the patient may meet with an
anesthesiologist to discuss any health conditions that
might affect the administration of anesthesia.

Aftercare
Aftercare for skin traction involves making sure the
limb stays aligned, and caring for the skin so that it does
not become sore and irritated. The patient should also
be alert to any swelling or tingling in the limb that would
suggest that the limb has been wrapped too tightly.
Aftercare for skeletal traction is more complex.
The patient is likely to be immobile for an extended
period. Deep breathing exercises are taught so that
respiratory function is maintained during this time of
little activity. Patients are also encouraged to do
range-of-motion exercises with the unaffected parts
of the body. The patient is taught how to use a trapeze
GALE ENCYCLOPEDIA OF MEDICINE

Traction

Simple traction

Gallows traction

Hamilton Russell traction

Balanced skeletal traction

Traction refers to the usage of a pulling force and special devices, such as a cast or splint, to treat muscle and skeletal disorders.
It is used to treat fractures, dislocations, and long-duration muscle spasms, and to prevent or correct deformities. The
illustration above features several commonly used forms of traction. (Illustration by Electronic Illustrators Group.)

(an overhead support bar) to shift on and off a bedpan, since it is not possible to get up to use the toilet. In
serious injuries, traction may be continued for several
months until healing is complete.

the development of bed sores, reduced respiratory
function, urinary problems, and circulatory problems.
Occasionally, fractures fail to heal. Being confined to
traction for a long period can take a an emotional toll
on the patient, also.

Risks
The main risks associated with skin traction are that
the traction will be applied incorrectly and cause harm,
or that the skin will become irritated. There are more
risks associated with skeletal traction. Bone inflammation may occur in response to the introduction of foreign
material into the body. Infection can occur at the pin
sites. If caught early, infection can be treated with antibiotics, but if severe, it may require removal of the pin.
Both types of traction have complications associated with long periods of immobility. These include
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
When correctly applied, traction generally produces very good, if slow, results.
Resources
BOOKS

‘‘Traction.’’ In Everything You Need to Know AboutMedical
Treatments. Springhouse, PA: Springhouse Corp.,1996.

Tish Davidson, A.M.
3753

Traditional Chinese medicine

Traditional Chinese medicine
Definition
Traditional Chinese medicine (TCM) is an ancient
and still very vital holistic system of health and healing, based on the notion of harmony and balance, and
employing the ideas of moderation and prevention.

Purpose
TCM is a complete system of health care with its
own unique theories of anatomy, health, and treatment.
It emphasizes diet and prevention and using acupuncture, herbal medicine, massage, and exercise; and focuses
on stimulating the body’s natural curative powers.

Precautions
In situations of severe trauma, TCM should not be
substituted for contemporary modern trauma practice;
it is most useful as an adjunct to the healing regimen.
TCM is not the first line of treatment for bacterial
infection or cancer, but may usefully complement contemporary medical treatment for those conditions.

Description
In theory and practice, traditional Chinese medicine
is completely different from Western medicine, both in
terms of considering how the human body works and
how illness occurs and should be treated. As a part of a
continuing system that has been in use for thousands of
years, it is still employed to treat over one-quarter of the
world’s population. Since the earliest Chinese physicians
were also philosophers, their ways of viewing the world
and human beings role in it affected their medicine. In
TCM, both philosophically and medically, moderation
in all things is advocated, as is living in harmony with
nature and striving for balance in all things. Prevention
is also a key goal of Chinese medicine, and much emphasis is placed on educating the patient to live responsibly.
The Chinese physician also is more of an advisor than an
authority; he or she believes in treating every patient
differently, based on the notion that one does not treat
the disease or condition but rather the individual
patient. Thus two people with the same complaint may
be treated entirely differently, if their constitutions and
life situations are dissimilar. Disease is also considered
to be evidence of the failure of preventive health care and
a falling out of balance or harmony.
There is some confusion in the West about the
fundamental philosophical principles upon which
3754

traditional Chinese medicine is based – such as the
concept of yin and yang, the notion of five elements
(wood, fire, earth, metal and water), and the concept
of chi–yet each can be explained in a way that is
understandable to Westerners.
Yin and yang describe the interdependent relationship of opposing but complementary forces believed to
be necessary for a healthy life. Basically, the goal is to
maintain a balance of yin and yang in all things.
The five elements, or five phase theory, is also
grounded in the notion of harmony and balance. The
concept of chi, which means something like ‘‘life
force’’ or ‘‘energy,’’ is perhaps most different from
Western ideas. TCM asserts that chi is an invisible
energy force that flows freely in a healthy person, but
is weakened or blocked when a person is ill.
Specifically, the illness is a result of the blockage,
rather than the blockage being the result of the illness.
Besides these philosophical concepts that differ
considerably from infection-based principles of medicine and health, the methods employed by traditional
Chinese medicine are also quite different. If allopathic
Western practitioners could be described as interventionist and dependent on synthetic pharmaceuticals,
TCM methods are mostly natural and noninvasive.
For example, where Western physicians might employ
surgery and chemotherapy or radiation for a cancer
patient, a TCM physician might use acupuncture and
dietary changes. TCM believes in ‘‘curing the root’’ of
a disease and not merely in treating its symptoms.
Another major difference is how the patient is
regarded. In Western medicine, patients with similar
complaints or diseases, usually will receive virtually
the same treatment. In TCM however, the physician
treats the patient and not the condition, believing that
identical diseases can have entirely different causes. In
terms of the principles upon which it is based and the
methods used, traditional Chinese medicine, therefore, is considered by many in the West to be a radically different system of health care.
To some in the Western world, this very strangeness is the reason why it might be attractive. To others,
tired of what they perceive as their physician’s perfunctory, analytical, and sometimes cold manner,
TCM offers a more humane, patient-oriented
approach that encourages a high degree of practitioner-patient interaction and is not overly dependent
on technology.
For example, during a consultation with a TCM
practitioner, the patient will receive a considerable
amount of time and attention. During the important
GALE ENCYCLOPEDIA OF MEDICINE

First, the practitioner will ask many questions,
going beyond the typical patient history to inquire
about such particulars as eating and bowel habits or
sleep patterns. Next, the physician looks at the patient,
observing his or her complexion and eyes, while also
examining the tongue very closely, believing that it is a
barometer of the body’s health and that different areas
of the tongue can reflect the functioning of different
body organs. After observing, they listen to the
patient’s voice or cough and then smell his or her
breath, body odor, urine, and even bowel movements.
Finally, the practitioner touches the patient, palpating
his or her abdomen and feeling the wrist to take up to
six different pulses. It is through these different pulses
that the well-trained practitioner can diagnose any
problem with the flow of the all-important chi.
Altogether, this essentially observational examination
will lead the physician to diagnose or decide the
patient’s problem. This diagnosis is very different
from one in contemporary Western medicine. No
blood or urine samples are tested in a laboratory.
The key to this technique lies in the experience and
skill of the practitioner.
After making a diagnosis, the physician will suggest a course of treatment from one or all of the available TCM methods. These fall into four main
categories: herbal medicine, acupuncture, dietary
therapy, and massage and exercise. A typical TCM
prescription consists of a complex variety of many
different herbal and mineral ingredients. Chinese herbal remedies are intended to assist the body’s own
systems so that eventually the patient can stop taking
them and never becomes dependent on them. Herbal
formulas are usually given as teas, which differ according to the patient.
Other common techniques used in a TCM prescription are as follows:


Acupuncture is based on the notion that the body’s
vital energy force, chi, travels through known channels or ‘‘meridians.’’ The acupuncturist inserts tiny,
thin sterile needles at particular, selected points on
the body to unblock or correct the flow of energy.
These needles are hardly felt as they are inserted and
are left in place for 15 to 20 minutes. Some patients
report immediate improvement, others feel exhilarated, while some feel like sleeping. In some cases,
patients say their condition worsens before it
improves. No contemporary scientific explanation
exists as to how or why acupuncture works.

GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Allopathic—Pertaining to conventional medical
treatment of disease symptoms that uses substances
or techniques to oppose or suppress the symptoms.
Anatomy—The science of the body structure of an
organism and its parts.
Holistic—That which pertains to the entire person,
including the mind, body, and spirit.
Palpate—To examine the body by touching or
pressing with the fingers or the palm of the hand.
Pharmaceutical—Pertaining to drugs.
Therapeutic—Curative or healing.
Trauma—Injury or damage to the body.



Moxibustion is a variation sometimes employed.
Moxibustion is the slow burning on or over the
body of special herbal ‘‘cones.’’ These are placed
on specific acupoints and provide penetrating,
relaxing heat.



Massage is often recommended, and a deep finger
pressure technique known as acupressure is often
used to promote the proper flow of chi.



Diet is considered essential to good health, and
what might be called ‘‘kitchen medicine’’ is just
another aspect of herbalism. One example is a delicious DQ black bean soup that is traditionally eaten
by women in China after childbirth and each menstrual cycle.



Therapeutic exercises are sometimes prescribed as
well. In both the exact and flowing movements of
tai chi, and the breathing techniques of Qi Dong
exercise is considered essential to relieving stress
and promoting the smooth flow of chi.

As a system of total health care, TCM is prepared
to deal with any physical or mental problem, condition, or disease. However, unlike Western medicine at
its best, TCM is not able to render the kind of emergency crisis intervention that saves lives during physical traumas. Nonetheless, it works best at achieving its
goal of practicing preventive medicine. It has proven
effective in treating many types of aches and pains and
in helping people with depression and fatigue, as well
as circulation and digestive problems. Overall, its
emphasis on good diet and exercise, as well as on
individual responsibility and moderation in all things,
suggest that it is grounded in fundamentally sound
principles.
3755

Traditional Chinese medicine

first visit, the practitioner will conduct four types of
examinations, all extremely observational and all
quite different from what patients usually experience.

Trager psychophysical integration

Risks
In the hands of a qualified practitioner, TCM is
very safe. However, there is a small chance of not only
getting an infection from acupuncture, but also that an
existing infection could be spread to other parts of the
body by increased blood flow and circulation.

Normal results
Traditional Chinese medicine seeks to harmonize and rebalance the entire human system rather
than to treat just symptoms. Since proper internal
balance is considered to be the key to human health,
TCM strives to cure disease by restoring that balance
and therefore allowing the body to repair itself. Its
continuing medical goal is to detect and correct
abnormalities before they cause permanent physical
damage.
Resources
ORGANIZATIONS

American Academy of Medical Acupuncture. 2520 Milvia
St., Berkeley, CA 94704. (415) 841-3220.
American Association of Acupuncture & Oriental Medicine.
4101 Lake Boone Trail, Suite 201, Raleigh, NC 27607.
(919) 787-5181.

Leonard C. Bruno, PhD

M I L T O N T R A G E R (1909–1997)
Milton Trager was a medical doctor and a somatic
educator, specializing in body learning. He was a contemporary of F. Matthias Alexander, Moshe Feldenkrais,
and Ida Rolf.
As a young man in the 1920s, he occupied himself
with gymnastics and boxing. Through his intensely physical pursuits, he arrived at his self-taught body learning
theories. The techniques that he nurtured emphasized
body control over strength, prowess, and endurance.
For example, in striving to leap as high as possible,
Trager focused his concentration on landing as softly as
possible. He obtained a degree in physical medicine
before serving in the military during World War II.
Upon his return, Trager funded his medical school
education with his GI benefits. He established a private
practice and spent the ensuing 50 years refining his body
learning techniques and assisting afflicted individuals in
the process. When Trager’s father was stricken with sciatic pain, Trager learned to relieve the spasms by hand. In
time he learned to alleviate the symptoms of polio victims and others who suffered from muscle spasms.
Trager established the Trager Institute in the 1970s to
propagate the techniques that he had developed. By the
year 2000, an estimated 2,000 students and practitioners
had embraced the Trager Approach.
Trager lived with his wife, Emily, in Southern
California at the time of his death in January 1997.

Purpose

Trager psychophysical
integration
Definition
Trager psychophysical integration therapy, also
known as the Tragerwork system of physical integration, is a combination of hands-on tissue mobilization,
relaxation, and movement reeducation called
Mentastics. The underlying principle of psychophysical integration is that clients learn to be lighter, easier,
and freer by experiencing lightness, ease, and freedom
of movement in their bodies.
The Trager method is a psychologically grounded
physical approach to muscle relaxation, which is
induced when a practitioner and patient achieve a
state of mind called hook-up. Hook-up is described
as a connection to a state of grace or a powerful and
nourishing life force. It is the opposite of strain or
effort.
3756

Psychophysical integration therapy has been helpful in relieving muscle discomfort in patients afflicted
with polio, muscular dystrophy, Parkinson’s disease,
multiple sclerosis, post-stroke trauma, and psychiatric
disturbances. The therapy is useful in alleviating such
chronic conditions as back and leg pain. Athletes may
benefit from this system to increase resilience to injuries and to improve their mental attitudes. In addition,
the Trager Institute maintains that Tragerwork helps
clients achieve greater mental clarity through the
release of ‘‘deep-seated physical and mental patterns.’’

Description
Origins
Psychophysical integration therapy began with
Dr. Milton Trager (1908–1997), who earned a medical
degree in midlife after working out his approach to
healing chronic pain. Trager was born with a spinal
GALE ENCYCLOPEDIA OF MEDICINE

Hook-up—A state of effortless connection with a
life-enhancing force. Trager practitioners enter a
state of hook-up before working with clients in
order to focus on their needs. Trager himself
described hook-up as a meditative process of
‘‘becoming one with the energy force that surrounds all living things.’’
Mentastics—The active phase of Trager therapy.
Mentastics are a form of movement reeducation in
which clients learn to reexperience movement as
pleasurable and positive.
Tablework—The passive phase of Trager therapy,
in which the practitioner uses gentle and noninvasive movements to allow the client to relax deeply
and experience physical movement as free and
effortless.

allow the client ‘‘slowly to give up muscular and mental control and sink into a very deep state of relaxation
not unlike that experienced in hypnosis.’’
Mentastics
Mentastics are free-flowing dance-like movements intended to increase the client’s self-awareness,
as well as providing tools to help the client move
through and control chronic pain. The client is encouraged to ‘‘let go,’’ which means that they are asked to
begin a movement, then release their muscle tension
and allow the weight of the body part involved to
complete the motion. By experiencing movement as
something pleasurable and positive rather than painful or negative, clients begin to loosen up, learn new
movements more easily, and even begin inventing their
own. In the early stages of treatment, clients are
advised to do Mentastic movements at home for
10–15-minute sessions, three times per day.

Preparations
deformity and overcame it through practicing a variety of athletic exercises. At the time that he discovered
his approach to bodywork, he was training to become
a boxer. His therapy came to public attention when
Esalen Institute in California, the famous center of the
human potential movement, invited him to give a
demonstration of his technique during the mid1970s. Trager abandoned his private medical practice
in 1977 to devote full energy to the development and
further understanding of psychophysical integration.
The Trager Institute, which continues his work, was
founded in 1980.
The Trager method consists of two parts, a passive aspect referred to as tablework and an active
aspect called Mentastics, which is a self-care exercise
program. Although the benefits of the Trager
approach are said to be cumulative, practitioners and
clients appear to be free to set their own schedules for a
series of sessions. There is no minimum number of
sessions that clients must agree to take.
Tablework
The tablework is performed on a comfortable
padded table. Sessions last about 60–90 minutes. The
practitioner moves the client in ways that he or she
naturally moves, in such a way that he or she experiences how it feels to move effortlessly and freely on
one’s own. The movements resemble general mobilization techniques, and incorporate some manual, cervical, and lumbar traction. The goal of tablework is to
GALE ENCYCLOPEDIA OF MEDICINE

Prior to a session of tablework, the client dresses
for comfort, ‘‘with a minimum of swimwear or briefs,’’
according to the Trager Institute. The client is also
covered with a drape. No oils or lotions are used.
The practitioner prepares for the session by clearing his or her mind of everything but the client, until he
or she achieves a state of hook-up. This attitude of
‘‘relaxed meditative awareness’’ on the part of the
practitioner is one of the unique features of
Tragerwork. It is described as allowing the therapist
‘‘to connect deeply with the recipient in an unforced
way and enables the practitioner to perceive the slightest responses from the [client’s] body.’’

Precautions
Because of the unusual sensitivity and heightened
awareness that is associated with the practitioner’s
touch, pain should never result from tablework sessions. It is important for clients to alert the practitioner to any pain associated with either the
tablework or the Mentastics program.
Although the movements used in Trager tablework are gentle and noninvasive, clients who have
had recent injuries or surgery should wait to heal
before undertaking a course of Tragerwork.

Side effects
The Trager method should not produce physical
side effects when employed by a qualified practitioner.
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Trager psychophysical integration

KEY TERMS

Transcranial Doppler ultrasonography

It is possible that some clients may have emotional
reactions associated with the release of physical patterns acquired as a response to trauma, but such reactions are unusual.

Research and general acceptance
Tragerwork, like other forms of bodywork, has
gained increasing acceptance as a form of treatment since the 1980s. In 2000 there were 1,200
certified psychophysical integration practitioners
in 15 countries worldwide. The therapy has been
reported as a commonly employed treatment for
mainstream athletes. In addition, the National
Institutes of Health lists psychophysical therapy
as a mind-body form of complementary alternative
medicine.
Resources
ORGANIZATIONS

Florida Institute of Psychophysical Integration: Quantum
Balance. 5837 Mariner Drive. Tampa, FL 33609-3411.
(813) 186-2273. Fax: (813) 287-2870.
Trager Institute. 21 Locust Avenue. Mill Valley, CA 949412806. (415) 388-2688. Fax: (415) 399-2710. admin@
trager.com. <http://www.trager.com>.

Gloria Cooksey

Tranquilizers see Antianxiety drugs

The flow of blood through the arteries in the brain
can be analyzed using transcranial Doppler ultrasonography (TCD). TCD is a form of ultrasound, in which
high frequency sound waves bounce off or pass
through body tissues. While most other types of ultrasonography create images of the tissue being studied,
the results of TCD are audible sounds that the examiner listens to and records.
Doppler ultrasonography uses what is called the
Doppler effect to measure the rate and direction of
blood flow in the vessels. Just as a siren’s pitch sounds
higher when its source is moving toward you and
lower as it moves away, so too will ultrasound waves
change pitch, or frequency, as they bounce off the red
blood cells moving in the blood. It is these pitch
changes that produce the audible sounds during the
exam.
Changes in frequency can be used to measure both
the direction and the speed of blood flow. Faster blood
flow causes a greater change in frequency. Combined
with other tests, this information can be used to locate
restrictions in the blood vessels in the brain, and to
track changes in blood flow over time. In this way,
TCD gives valuable information about the site of a
stroke and the patient’s progress after a stroke. TCD is
also used to evaluate the contraction of blood vessels
that can occur if a blood vessel ruptures.

Precautions
Ultrasonography procedures are safe, noninvasive, and painless. No special precautions are
necessary.

Transcranial Doppler
ultrasonography
Definition
Transcranial Doppler ultrasonography is a noninvasive method of analyzing blood flow in the brain.

Purpose
The blood that flows through the brain distributes
nutrients to the brain and removes wastes. This flow
maintains the high rate of metabolism necessary for
the brain to function. Restrictions in blood flow may
occur from vessel narrowing (stenosis), clot formation
(thrombosis), blockage (embolism), or blood vessel
rupture (hemorrhage). Lack of sufficient blood flow
(ischemia) threatens brain tissue and may cause a
stroke.
3758

Description
TCD is done with either one or two probes
placed against the skin. The examiner spreads a
clear gel on the areas of the head where the probe
will be placed. Usually, the probes are placed on the
temple, on the base of the skull at the back of the
neck, and over the closed eyelid. In these places,
there is the least amount of thick protective bone
and the sound waves can penetrate the best. The
examiner adjusts the probe position and orientation
to direct the sound waves toward the blood vessels of
interest. Finding the best approach may take some
time. A compression test may be performed during
the exam. In this test, the main artery in the neck
(carotid artery) is briefly compressed, and changes in
blood flow patterns are observed. A full TCD exam
may last 30–45 minutes, and often longer in patients
with disease.
GALE ENCYCLOPEDIA OF MEDICINE

No special preparation is needed. The patient
should remove contact lenses, and may wish to avoid
the use of eye makeup, since the gel is likely to smear it.

Aftercare
The gel is washed off with soap and water. No
other after care is needed.

Risks
TCD is noninvasive and has no risks. A compression test is occasionally, though very rarely, hazardous
for a patient with narrowed arteries (atherosclerosis),
since the increased pressure may dislodge a piece of the
substance that causes the narrowing (plaque).

Normal results
TCD produces an audible sound that varies with
the heartbeat. It also varies depending on the direction
and rate of flow through the vessel being examined.
Each of the vessels in the brain has a characteristic
direction of flow, which can be detected by TCD. Flow
rates are somewhat variable from person to person.

Abnormal results
Lack of flow indicates a vessel has been completely blocked (although absence of a signal may also be
due to absorption of sound waves by bone). If blood
flows in the wrong direction or alternates between
normal and reverse flow, it may mean there is a blockage elsewhere. This happens because blood is rerouted
due to abnormalities in pressure caused by the
blockage.
If the speed of flow is increased, it may mean that
blood is flowing through a restricted area that is just
‘‘upstream’’ from the probe. Intuitively, one might
think that a restricted blood vessel would cause the
speed of blood flow to slow down. However, the
opposite is true. This is because the same amount of
blood going through a narrower opening must go
faster. Increased speed is also seen if a vessel is carrying rerouted blood.
Resources
BOOKS

Samuels, Martin, and Steven Feske, editors. Office Practice
of Neurology. New York: Churchill Livingstone, 1996.

Richard Robinson
GALE ENCYCLOPEDIA OF MEDICINE

Transesophageal
echocardiography
Definition
Transesophageal echocardiography is a diagnostic
test using an ultrasound device that is passed into the
esophagus of the patient to create a clear image of the
heart muscle and other parts of the heart. A tube with
a device called a transducer is passed down into the
patient’s throat and into the esophagus (the food tube
that connects the mouth to the stomach). The transducer directs ultrasound waves into the heart, and the
reflected sound waves picked up by the transducer are
translated into an image of the heart.

Purpose
Since the esophagus is right next to the heart,
transesophageal echocardiography provides a very
clear picture of the heart. It can provide information
on the size of the heart, its pumping strength, and the
location and extent of any damage to its tissues. It can
detect abnormal tissue growth around the heart
valves. It is also good at detecting abnormalities in
the pattern of blood flow, such as the backward flow
of blood through partly closed heart valves, known as
regurgitation or insufficiency. It is especially useful in
cases in which conventional echocardiography (a test
where the transducer is kept on the patient’s chest)
cannot offer a good image, such as when the patient
is obese or has a thick chest wall. It is useful for
monitoring heart function during cardiac surgery
and detecting blood clots in the left atrium of the heart.

Precautions
Patients should avoid consuming alcohol for
a day or so before the procedure, since alcohol
may amplify the effects of the sedative used with the
procedure.

Description
Echocardiography creates an image of the heart
using ultra-high-frequency sound waves–sound waves
that are much too high in frequency to be heard by the
human ear. The technique is very similar to ultrasound
scanning commonly used to visualize the fetus during
pregnancy.
A transesophageal echocardiography examination generally lasts 30–60 minutes. The patient is
given a mild sedative and the back of the throat is
3759

Transesophageal echocardiography

Preparation

Transfusion

sprayed with a local anesthetic, in order to suppress
the gag reflex. Next, a special viewing tube called an
endoscope, containing a tiny transducer, is passed
through the mouth and into the esophagus. It is carefully moved until it is positioned directly next to the
heart. Essentially a modified microphone, the transducer directs ultrasound waves into the heart, some
of which get reflected (or ‘‘echoed’’) back to the
transducer. Different tissues and blood all reflect
ultrasound waves differently. These sound waves
can be translated into a meaningful image of the
heart, which is displayed on a monitor or recorded
on paper or tape. The transducer may be moved
several times during the test to help doctors get a
better view of the heart.

KEY TERMS
Endoscope—An instrument used to see and examine the inside of a body cavity or organ.
Gag reflex—A normal reflex consisting of elevation
of the palate, retraction of the tongue, and contraction of the throat muscles.
Regurgitation—Backward flow of blood through a
partly closed valve.
Transducer—A device that converts electrical signals into ultrasound waves and ultrasound waves
back into electrical impulses.
Ultrasound—Sound waves at a frequency of
20,000 kHz, often used for diagnostic imaging.

Preparation
The patient may be given a mild sedative before
the procedure, and an anesthetic is sprayed into the
back of the throat in order to suppress the gag reflex.

Aftercare
After the test, it is important to refrain from eating or
drinking until the gag reflex has returned–otherwise, the
patient may accidentally inhale some of the food or beverage. If a sedative has been given, patients should not
drive or operate heavy machinery for at least 10-12 hours.
They should avoid consuming alcohol for a day or so,
since alcohol may amplify the effect of the sedative.

abnormalities can include blood leaking backward
through the heart valves (regurgitation), or blood
clots in the left atrium of the heart.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Risks
Transesophageal echocardiography may cause
gagging and discomfort when the transducer is passed
down into the throat. Patients may also experience sore
throat for a few days after the test. In rare cases, the
procedure may cause bleeding or perforation of the
esophagus or an inflammatory condition known as
infective endocarditis. The patient may have an adverse
reaction to the sedative or local anesthetic.

Normal results
A normal transesophageal echocardiogram shows
a normal heart structure and the normal flow of blood
through the heart chambers and heart valves.

Robert Scott Dinsmoor

Transferrin test see Iron tests

Transfusion
Definition
Transfusion is the process of transferring whole
blood or blood components from one person (donor)
to another (recipient).

Abnormal results
A transesophageal echocardiogram may show a
number of abnormalities in the structure and function
of the heart, such as thickening of the wall of the heart
muscle (especially the left ventricle). Other
3760

Purpose
Transfusions are given to restore lost blood, to
improve clotting time, and to improve the ability of
the blood to deliver oxygen to the body’s tissues.
GALE ENCYCLOPEDIA OF MEDICINE

For donors, the process of giving blood is very safe.
Only sterile equipment is used and there is no chance of
catching an infection from the equipment. There is a
slight chance of infection at the puncture site if the skin
is not properly washed before the collection needle is
inserted. Some donors feel light-headed upon standing
for the first time after donating. Occasionally, a donor
will faint. Donors are advised to drink lots of liquids to
replace the fluid lost with the donated blood. It is
important to maintain the fluid volume of the blood
so that the blood pressure will remain stable. Strenuous
exercise should be avoided for the rest of the day. Most
patients have very slight symptoms or no symptoms at
all after donating blood.
For recipients, a number of precautions must be
taken. The blood given by transfusion must be matched
with the recipient’s blood type. Incompatible blood
types can cause a serious adverse reaction (transfusion
reaction). Blood is introduced slowly by gravity flow
directly into the veins (intravenous infusion) so that
medical personnel can observe the patient for signs of
adverse reactions. People who have received many
transfusions can develop an immune response to some
factors in foreign blood cells (see below). This immune
reaction must be checked before giving new blood.
Infectious diseases can also be transmitted through
donated blood.

Description
Either whole blood or blood components can be
used for transfusion. Whole blood is used exactly as it
was received from the donor. Blood components are
parts of whole blood, such as red blood cells (RBCs),
plasma, platelets, clotting factors, immunoglobulins,
and white blood cells. Whole blood is used only when
needed or when components are not available. Most
of the time whole blood is not used because the
patient’s medical condition can be treated with a
blood component and too much whole blood can
raise a recipient’s blood pressure. High blood pressure
can have medical side effects and should be avoided.
Use of blood components is a more efficient way to use
the blood supply, because blood that has been processed (fractionated) into components can be used to
treat more than one person. Each year, more than 20
million units of blood or blood products are transfused in the United States.
Whole blood is generally used when a person has
lost a lot of blood. Such blood loss can be caused by
injury or surgical procedures. Whole blood is given to
GALE ENCYCLOPEDIA OF MEDICINE

help restore the blood volume, which is essential for
maintaining blood pressure. Whole blood is also given
to ensure that the body’s tissues are receiving enough
oxygen. Whole blood is occasionally given when a
required blood component is unavailable in isolated
form.
Red blood cells are the blood component most
frequently used for transfusion. RBCs are the only
cells in the body that transport oxygen. A transfusion
of RBCs increases the amount of oxygen that can be
carried to the tissues of the body. RBCs that have been
separated from the liquid plasma (packed RBCs) are
given to people who have anemia or who have lost a
lot of blood. Platelets are another component frequently given by transfusion. Platelets are a key factor
in blood clotting. The clear fluid that carries blood
cells (plasma) also contains blood-clotting factors.
The platelets and plasma clotting factors are extracted
from donated blood and concentrated for use. These
factors are used to treat people with such clotting
disorders as hemophilia. Immunoglobulins, also
called gamma globulin or immune serum, are collected
from plasma for use in temporarily boosting the
immune capability of a patient. White blood cells
(WBCs) are another infection-fighting component of
the blood. White blood cells are given by transfusion
only rarely.
Blood donation
Each year in the United States, about 14,000,000
pints of blood are donated. Blood collection is strictly
regulated by the U.S. Food and Drug Administration
(FDA). The FDA has rules for the collection, processing, storage, and transportation of blood and blood
products. In addition, the American Red Cross,
United Blood Services, the American Association of
Blood Banks, and most states have specific rules for
the collection and processing of blood. The main purpose of regulation is to ensure the quality of blood and
to prevent the transmission of infectious diseases
through donated blood. Before blood and blood products are used, they are extensively tested for such
infectious agents as hepatitis and AIDS.
DONORS. Blood donors are questioned about
their general health, their lifestyle, and any medical
conditions that might disqualify them as donors.
These conditions include hepatitis, AIDS, cancer,
heart disease, asthma, malaria, bleeding disorders,
and high blood pressure. Screening prevents blood
donation by people who could transmit diseases or by
people whose medical condition would place them at
risk if they donated blood.

3761

Transfusion

Precautions

Transfusion

The blood pressure, temperature, and pulse of
donors are taken to ensure that they are physically
able to donate blood. One pint (450 ml) of blood is
usually donated, although it is possible to donate
smaller volumes. The average man has 10-12 pints
and the average woman 8-9 pints of blood. Within
hours after donating, most people have replaced the
fluid lost with the donated blood, bringing their blood
volume back to normal. Replacing donated blood cells
and platelets can take several weeks. People with low
blood pressure or anemia, and pregnant women
should not donate blood or should limit the amount
of blood they donate. Generally, people are allowed to
donate blood only once every two months. This delay
ensures the health of the donor and discourages people
from selling their blood. The practice of paying donors
for blood has essentially stopped. Donors who sell
blood tend to have a high risk for the transmission of
infectious agents.
BLOOD COLLECTION. Blood is collected from the

donor by inserting a large needle into a vein in the arm.
Usually, one of the larger veins near the inside of the
elbow is used. A tourniquet is placed on the upper arm
to increase the pressure in the arm veins and make
them swell and become more accessible. Once a suitable vein is identified, the area where the needle will be
inserted is sterilized by washing with soap solution or
an iodine-containing antiseptic. Sometimes both are
used. The donor lies on a bed or cot during the procedure, which takes about 10 minutes. Generally, an
18-gauge needle is used. This needle can easily fit
into the veins and yet is large enough that the blood
flows easily. Blood will sometimes clot in a smaller
needle and stop flowing. Blood is collected in sterile
plastic bags that hold one pint (450 ml). The bags
contain an anticoagulant to prevent clotting and preservatives to keep the blood cells alive. Properly
handled and refrigerated, whole blood can last for 42
days. While emphasis has been on screening of blood
donors and testing of blood products before they are
released for transfusion, the emphasis is beginning to
shift to future techniques designed to cleanse the blood
and rid it of possible pathogens or reactants.
AUTOLOGOUS TRANSFUSION. Autologous transfusion is a procedure in which patients donate blood
for their own use. Patients who are to undergo surgical
procedures for which a blood transfusion might be
required may elect to donate a supply of blood for
the purpose ahead of time. The blood is stored at the
hospital for the exclusive use of the patient. This procedure assures that the blood type is an exact match. It
also assures that no infection will be transmitted
through the blood transfusion.

3762

DIRECTED DONATION. Directed donors are family
or friends of the patient who needs a transfusion.
Some people think that family and friends provide a
safer source of blood than the general blood supply.
Studies do not show that directed donor blood is any
safer. Blood that is not used for the identified patient
becomes part of the general blood supply.
APHERESIS. Apheresis is a special procedure in
which only the necessary components of a donor’s
blood are collected. The remaining components are
returned to the donor. A special blood-processing
instrument is used in apheresis. It separates the blood
into components, saves the desired component, and
pumps all the other components back into the donor.
Because donors give only part of their blood, they can
donate more frequently. For example, people can give
almost 10 times as many platelets by apheresis as they
could give by donating whole blood.
BLOOD PROCESSING. A sample of the donator’s
blood is collected at the time of donation and tested
for infectious diseases. Blood is not used until the
results from these tests confirm that it is safe.
BLOOD TYPING. The donated blood is typed.
There are major and minor blood types, also called
blood groups. The major types are classified by the
ABO system. This system groups blood by two substances, called antigen A and antigen B, in the red
blood cells. The four ABO blood types are A, B, AB,
and O. Type A blood has the A antigen, type B has the
B antigen, type AB has both, and type O has neither.
These four types of blood are further sorted by the Rh
factor. The Rh, or rhesus factor, is also an antigen in
the red blood cells. A person who has the Rh factor is
Rh positive; a person who does not have the factor is
Rh negative. If a person has red blood cells with both
the B and the Rh antigens, that person is said to have a
B positive (B+) blood type. Blood types determine
what blood a patient can receive. Often, patients are
limited to receiving only blood of the same ABO and
Rh type as their own. An exception is type O, which
can be transfused to people of other types. Those who
are Rh negative can only receive Rh negative blood
(Rh positive recipients also can safely receive Rh negative blood of a compatible ABO type.) This means that
people with O negative blood are considered universal
donors; their blood type always is in demand at blood
centers.

Blood can be typed by several other minor antigens, such as Kell, Duffy, and Lewis. These minor
antigens can become important when a patient has
received many transfusions. These patients tend to
build up an immune response to the minor blood
GALE ENCYCLOPEDIA OF MEDICINE

Blood components used in transfusion
Most blood collected from donors is broken down
(fractionated) into components that are used to treat
specific problems or diseases. Treating patients with
blood components is the most efficient way to use the
blood supply.
RED BLOOD CELLS. Red blood cells (RBCs) carry
oxygen throughout the body. They obtain oxygen as
they pass through the lungs and give up oxygen to the
other tissues of the body as they are pumped through
arteries and veins. When patients do not have enough
RBCs to properly oxygenate their bodies, they can be
given a transfusion with RBCs obtained from donors.
RBCs are recovered from whole blood after donation.
They are then typed, removed from the watery blood
plasma to minimize the volume (packed), and stored.
They are given to people who have anemia (including
thalassemia), whose bone marrow does not make
enough RBCs, or who have other conditions that
decrease the number of RBCs in the blood.
Occasionally, red blood cells from rare blood types
are frozen. Once frozen, RBCs can survive for as
long as 10 years. Packed RBCs are given in the same
manner as whole blood.
PLASMA. Plasma is the liquid portion of blood. It
contains many useful proteins, especially clotting factors and immunoglobulins. After they are processed,
plasma or plasma factors (fractions) are usually frozen. Some plasma fractions are freeze-dried. These
fractions include clotting factors I through XIII.
Some people have an inherited disorder in which the
body produces too little of the plasma clotting factors
VIII (hemophilia A) or IX (hemophilia B).
Transfusions of these clotting factors help people
with hemophilia stop bleeding. Frozen plasma must
be thawed before it is used and freeze-dried plasma
must be mixed with liquid (reconstituted). In both
cases, these blood fractions are usually small in
volume and can be injected by syringe and needle.
PLATELETS. Platelets are small bodies in the blood
that are essential for clotting. People who do not have
enough platelets have bleeding problems. People who
have lymphoma, leukemia, or thrombocytopenia, and

GALE ENCYCLOPEDIA OF MEDICINE

people who are receiving cancer therapy do not make
enough platelets. Platelets have a very short shelf life;
they must be used within five days of blood donation.
Platelets are packed into bags. A platelet transfusion is
given in the same manner as whole blood.
IMMUNOGLOBULINS. Immunoglobulins are the
infection-fighting fraction of blood plasma. They are
also known as gamma globulin, antibodies, and
immune serum. This blood fraction is given to people
who have difficulty fighting infections, especially people whose immune systems are depressed by diseases,
such as AIDS. Immunoglobulins are also used to prevent tetanus after cuts, to treat animal bites when
rabies infection is suspected, or to treat severe childhood diseases. Generally, the volume used is small,
and the immunoglobulins can be injected.
WHITE BLOOD CELLS. White blood cells (WBCs)
are another infection-fighting component of the
blood. On rare occasions, white blood cells are given
by transfusion to treat life-threatening infections.
Such transfusions are given when the WBC count is
very low or when WBCs are not functioning normally.
Most of the time, however, antibiotics are used in these
cases.

Preparation
A person receiving a transfusion is treated in
much the same way as a blood donor. The site where
the needle will be inserted is carefully washed with a
soap-based solution, followed by an iodine-containing
antiseptic. The skin is then dried and the transfusion
needle inserted into the recipient’s vein. During the
early stages of a transfusion, the recipient is monitored
closely to detect any adverse reactions. If no signs of
adverse reaction are evident, the patient is monitored
occasionally for the duration of the transfusion
period. Upon completion of the transfusion, a compress bandage is place over the needle-insertion site to
prevent bleeding.

Aftercare
Recipients of blood transfusion are monitored
during and after the transfusion for signs of adverse
reaction.

Risks
Adverse reaction to mismatched blood (transfusion reaction) and transmission of infectious disease
are the two major risks of blood transfusion.
Transfusion reaction occurs when antibodies in the
3763

Transfusion

groups that do not match their own. Upon receiving a
transfusion with a mismatched minor blood group,
they may have an adverse reaction. A third group of
antigens to which a patient can react are residues from
the donor’s plasma that have attached to the RBCs.
To eliminate this problem, the RBCs are rinsed to
remove plasma residues. These rinsed cells are called
washed RBCs.

Transhepatic biliary catheterization

KEY TERMS
ABO blood groups—A system in which human
blood is classified by whether the red blood cells
contain A or B antigens. Type A blood has the A
antigen; type B has the B antigen, AB has both, and
0 has neither.
Antibody—A simple protein produced by the body
to destroy bacteria, viruses, or other foreign bodies.
Production of each antibody is triggered by a specific antigen.
Antigen—A substance that stimulates the immune
system to manufacture antibodies (immunoglobulins). The function of antibodies is to fight off intruder cells, such as bacteria or viruses, in the body.
Antigens stimulate the blood to fight other blood
cells that have the wrong antigens. If a person with
blood type A is given a transfusion with blood type
B, the A antigens will fight the foreign blood cells as
though they were an infection.
Immunoglobulin—An antibody.
Infusion—Introduction of a substance directly into
a vein or tissue by gravity flow.
Injection—Forcing a fluid into the body by means
of a needle and syringe.
Rh (rhesus) factor—An antigen present in the red
blood cells of 85% of humans. A person with Rh
factor is Rh positive (Rh+); a person without it is Rh
negative (Rh-). The Rh factor was first identified in
the blood of a rhesus monkey.

recipient’s blood react to foreign blood cells introduced by the transfusion. The antibodies bind to the
foreign cells and destroy them (hemolytic reaction).
Transfusion reaction may also cause a hypersensitivity
of the immune system that, in turn, may cause tissue
damage within the patient’s body. The patient may
also have an allergic reaction to mismatched blood.
The first symptoms of transfusion reaction are a feeling of general discomfort and anxiety. Breathing difficulties, flushing, a sense of pressure in the chest, and
back pain may develop. Evidence of a hemolytic reaction can be seen in the urine, which will be colored
from the waste of destroyed red blood cells. Severe
hemolytic reactions are occasionally fatal. Reactions
to mismatches of minor factors are milder. These
symptoms include itchiness, dizziness, fever, headache,
rash, and swelling. Sometimes the patient will experience breathing difficulties and muscle spasms. Most
3764

adverse reactions from mismatched blood are not
life-threatening. The infectious diseases most often
acquired from blood transfusion in the United States
are hepatitis and AIDS.
Patients who are given too much blood can
develop high blood pressure, a concern for people
who have heart disease. Very rarely, an air embolism
is created when air is introduced into a patient’s veins
through the tubing used for intravenous infusion. The
danger of embolism is greatest when infusion is begun
or ended. Care must be taken to ensure that all air is
bled out of the tubing before infusion begins, and that
infusion is stopped before air can enter the patient’s
blood system.
Resources
PERIODICALS

Rushton, Alana R., and Patricia R. Jennings. ‘‘Issues in
Transfusion Safety: Predonation Screening and
Deferral Procedures and Postdonation Testing of
Blood Samples Protect the Safety of the Blood
Supply—but even with High Safety and Surveillance
Levels, Transfusion-related Transmission of Disease
Remains Possible..’’ Journal of the American Academy
of Physicians Assistants May 2004: 39–45.
OTHER

United Blood Services. <http://
www.unitedbloodservices.org>.

John T. Lohr, PhD
Teresa G. Odle

Transhepatic biliary
catheterization
Definition
Transhepatic biliary catheterization is a surgical
procedure during which a catheter is inserted into the
bile duct to relieve an obstruction.

Purpose
Bile is a fluid made in the liver and stored in the
gall bladder. The function of bile is to break down fats
during digestion. When fatty foods move into the
intestine, bile is released from the gall bladder, travels
through the bile duct, and enters the first part of the
small intestine (duodenum).
GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Transhepatic biliary catheterization is done when
cancer has progressed to the point where all the malignant cells cannot be removed by surgery. Patients who
need transhepatic biliary catheterization often suffer
from additional complications of their cancer.
Because of the likelihood of bleeding from the liver,
this procedure should not be done on patients who
have blood clotting abnormalities.

puncturing the liver. Infection may also result from
this procedure. Sometimes the catheter itself becomes
blocked and is ineffective.

Normal results
Transhepatic biliary catheterization is a treatment, not a cure. Successful treatment relieves the
blocked bile duct, but does not change the underlying
conditions that caused the blockage.
Resources
ORGANIZATIONS

National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
OTHER

‘‘Extrahepatic Bile Duct Cancer.’’ National Cancer Institute
Page. <http://www.nci.nih.gov>.

Tish Davidson, A.M.

Description
Transhepatic biliary catheterization is performed
by inserting a needle through the skin, into the abdomen, through the liver, and into the bile duct. A wire
attached to the needle then guides the catheter into
place. The procedure can take several hours. The
patient is given medication for pain.
The catheter can either reestablish bile flow into
the duodenum or reroute the bile so it drains into a bag
outside the body. The choice depends on the extent
and position of the obstruction.

Preparation
The standard preoperative blood tests are performed. The patient should not eat or drink the day
of the procedure.

Aftercare
The patient must stay in bed after the procedure
for at least six hours, to reduce the risk of bleeding. A
nurse checks vital signs and looks for indications of
complication such as pain, cramping, or leakage
around the catheter. The catheter is flushed periodically to keep it open. Patient and caregiver education
on how to keep the catheter clean and irrigated is an
important part of aftercare.

Risks
The most common complication of transhepatic
biliary catheterization is bleeding as a result of
GALE ENCYCLOPEDIA OF MEDICINE

Transient ischemic attack
Definition
A transient ischemic attack, or TIA, is often
described as a mini-stroke. Unlike a stroke, however,
the symptoms can disappear within a few minutes.
TIAs and strokes are both caused by a disruption of
the blood flow to the brain. In TIAs and most strokes,
this disruption is caused by a blood clot blocking one of
the blood vessels leading to the brain. The blockage
produces symptoms such as sudden weakness or numbness on one side of the body, sudden dimming or loss of
vision, and difficulty speaking or understanding speech.
If the symptoms are caused by a TIA, they last less than
24 hours and do not cause brain damage. Stroke-associated symptoms, on the other hand, do not go away
and may cause brain damage or death. TIAs can serve
as an early warning sign of stroke and require immediate medical attention.

Description
Strokes are the third leading cause of death in the
United States and the leading cause of disability.
Approximately 500,000-600,000 people have strokes
each year, and more than 160,000 die as a result.
About 85% of these strokes are classified as ischemic.
In ischemic stroke, a blood vessel leading to the brain
3765

Transient ischemic attack

If the bile duct is blocked, the skin becomes yellowish (jaundiced), the abdomen is painful, and a fever
develops. The bile duct can be blocked by gallstones,
surgical injury, infection in the duct, or by tissue growth
due to cancer. Transhepatic biliary catheterization is
performed to relieve bile duct blockage. The most common reason for this procedure is to relieve obstruction
from the overgrowth of cancer cells. Obstruction due to
gallstones is usually cleared by other means.

Transient ischemic attack

becomes blocked and an area of the brain is deprived
of oxygenated blood. (The other 15% of strokes are
caused by bleeding from a blood vessel that has ruptured.) Without the blood supply, the cells in that area
of the brain die. Since brain cells cannot grow back,
the functions that are controlled by that brain area
may be permanently lost.
Approximately 10% of strokes are preceded by one
or more TIAs. The estimated annual number of TIAs is
about 50,000; an exact count is difficult because TIAs
are not always reported. They may be under-reported
because they typically last less than an hour, perhaps
only for a few minutes. Because they are so brief, TIAs
may not seem important. However, an estimated onethird of all TIAs are followed by a stroke within five
years. They are considered a medical emergency and
prompt medical attention is very important.
Risk factors for strokes and TIAs are very similar.
The risk of a TIA or stroke is higher among men,
African Americans, people over age 65, and people
with heart disease or diabetes. Smokers, people with
high blood pressure, and people who are overweight
also have a greater risk for TIAs and strokes.

Causes and symptoms
A TIA is caused by a temporary blockage of one
of the arteries that leads into the brain. Small blood
clots, called microemboli, are the immediate cause of
the blockage. The blockage forms because of damage
or disease within the circulatory system. Blood clots
can form in blood vessels because of artery damage,
heart disease, and other cardiovascular problems. For
example, atherosclerosis is strongly associated with
TIAs. Atherosclerosis is the build-up of fatty deposits
or plaque at certain areas in the circulatory system.
Clotting cells in blood, called platelets, tend to stick to
atherosclerotic plaques or other damaged sites within
blood vessels. Occasionally, a clot may grow large
enough to block a blood vessel, or a piece of a clot
may break off and circulate to other areas of the body.
If a clot does not dissolve quickly enough, it can lodge
in a blood vessel and block it. In TIAs, the microemboli dissolve within a short time.
Blood flows into the brain through two main pathways: the carotid arteries and the vertebrobasilar
arteries. The carotid arteries are located on the front of
the neck; the vertebrobasilar arteries are at the base of
the skull at the back of the head. The symptoms produced by a TIA are determined by the arteries affected.
If a vertebrobasilar artery is blocked, common
symptoms include double vision and dizziness, nausea
3766

and vomiting, difficulty speaking, and problems understanding and using spoken words. There may also be a
numbness around the mouth and a tingling sensation
in the limbs. Blockage of a carotid artery produces
complete loss of vision, dimmed or foggy vision, and
paralysis or weakness on one side of the body. These
symptoms also may be accompanied by language problems and speech difficulty.
With either type of blockage, the microemboli
dissolve within hours and full function returns.

Diagnosis
The goal of diagnosis is to identify the precise
cause of the TIA and to recommend treatment.
Initial information that an individual can supply
includes a medical history, what drugs are currently
being taken and why, and a full description of the
symptoms. Blood tests are ordered to screen blood
counts — the numbers of specific blood cell types —
and to measure sugar and lipid (fats, including cholesterol) levels. Based on this information and a physical
examination that includes blood pressure, pulse, and
respiration measurements, one or more of the following imaging tests are ordered.
A computed tomography scan (CT scan) or a
magnetic resonance imaging (MRI) scan is usually the
first imaging test. CT or MRI can rule out other
problems, such as a tumor or subdural hematoma,
which can mimic the symptoms of a TIA. A CT scan
also can uncover aneurysms and arteriovenous malformation, both of which are blood vessel abnormalities that can cause bleeding in the brain.
Another useful imaging test is carotid ultrasonography, a noninvasive procedure that allows examination of the interior of the carotid artery. This
examination can detect carotid stenosis, a condition
in which the artery is abnormally narrow because of
atherosclerosis. Ultrasonography is very reliable in
identifying stenosis, but it does not give enough information to accurately assess the degree of stenosis.
Because the treatment used depends on the degree of
stenosis, treatment decisions cannot be based on ultrasonography. Another type of ultrasonography, called
transcranial doppler ultrasonography, is used to detect
stenosis of the blood vessels within the brain and in the
vertebrobasilar arteries.
If stenosis is identified, a further test called cerebral arteriography may be done. This test is not done if
the individual is in poor health, because it may be too
risky. Arteriography involves injecting a special dye
into the blood vessels that makes them visible on
GALE ENCYCLOPEDIA OF MEDICINE

Although TIAs affect the brain, the ultimate cause
of the problem may be found in the heart. Heart disease or damage to the heart’s blood vessels is assessed
by echocardiography. Echocardiography is a type of
ultrasonography and is a noninvasive procedure.

Treatment
Treatment is aimed at preventing further TIAs
and especially at preventing a stroke. The particular
therapy depends on the root cause of the TIA and is
not begun until this cause is identified. If at all possible, drug therapy is the preferred method of treating
TIAs. Surgical intervention may be required if an
individual’s situation is not likely to respond to medication or if medication has failed.
Aspirin often is chosen for drug therapy. It is sometimes called a blood thinner because it blocks the function of platelets, the sticky cells that trigger blood
clotting. Since aspirin can cause gastrointestinal side
effects, other drugs may be prescribed. These drugs
include dipyridamole or ticlopidine hydrochloride
(Ticlid). Dipyridamole, which works by relaxing the
smooth muscles of the arteries, is not as effective as
aspirin. Ticlopidine hydrochloride is an anti-platelet
drug that is slightly more effective than aspirin, especially in women. However, it may cause diarrhea or
lowered blood cell counts. Blood tests must, therefore,
be done frequently when patients are taking ticlopidine.
If carotid arteriography reveals at least a 70%
blockage of the carotid artery, surgical treatment
usually is recommended. The particular surgical
method is called carotid endarterectomy. In endarterectomy, the artery is opened and the material clogging
it is removed. Another procedure, called angioplasty,
has been suggested for treating carotid stenosis, but it
is not widely used. This procedure is performed by
threading a thin tube through the blood vessel to the
site that is clogged. A balloon or a stent (a slender rod)
is then passed through the tube to mechanically widen
the narrowed area. This procedure is successfully used
in other blood vessels in the body, but there is some
worry that using it close to the brain may be too
dangerous. Surgical treatment of blockage of the vertebrobasilar arteries is not usually recommended.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment of TIAs also focuses on underlying
problems. High blood pressure, heart disease, and
high levels of blood lipids all require medical intervention. Condition-specific medications often are
prescribed and lifestyle changes are strongly encouraged. These changes include giving up smoking or
excess alcohol consumption, engaging in physical
exercise, and eating sensibly.

Prognosis
One-third of TIAs are followed by stroke in the
next five years; in the other two-thirds, the TIAs may
either continue or disappear on their own. However,
because of the risk of stroke-related disability and
death, all TIAs should be treated as emergency medical situations. In 2003, researchers discovered a naturally occurring system in the bodies of those who have
TIAs that shields them from some of the brain damage
that might occur in a second stroke. The researchers
said that the changes in the brain that seem to protect
it are similar to those that occur in hibernating animals. They hope by studying the genetics of these
changes, they can develop medications that will help
protect the bodies of people who have not had TIAs. It
still is important to protect against further strokes
following a TIA, however.
Medical treatment significantly decreases the risk
of stroke for people who experience one or more TIAs.
Anti-platelet therapy with aspirin or ticlopidine may
reduce risk as much as 31%. Carotid endarterectomy
also substantially reduces stroke risk. The procedure
itself carries some risk, but the complication rate is less
than 5%. The risk of complication can be lowered by
choosing to have the procedure done in a facility
experienced with it and by a surgeon with a low complication rate.

Prevention
Treatment for TIAs is complemented by lifestyle changes. These practices also may prevent
TIAs and strokes from ever occurring. Doctors
and other health-care providers universally recommend that individuals stop smoking and consume
alcohol in moderation. Regular health checkups
can detect high blood pressure, heart disease, and
other underlying problems. Adhering to treatment
for these problems can help minimize TIA and
stroke risks. A Danish study seemed to confirm
in 2003 that eating more citrus fruit reduces the
risk of TIA and stroke. Finally, maintaining a
healthy weight and engaging in regular exercise
as able are strongly recommended.
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Transient ischemic attack

x rays. This procedure also is used to find suspected
problems with blood vessels in the brain. Because it is
an invasive procedure, complications may arise.
Typically, these complications are minor and temporary. In a very small percentage of people with cardiovascular disease, the procedure may cause serious
complications, such as stroke.

Transposition of the great arteries

Resources

KEY TERMS
Angioplasty—A medical procedure in which a
catheter, or thin tube, is threaded through blood
vessels. The catheter is used to place a balloon or
stent (a small metal rod) at an area of stenosis and
expand it mechanically.
Arteriography—A medical test in which an x-ray
visible dye is injected into blood vessels. This
dye allows the blood vessels to be imaged with
x rays.
Atherosclerosis—A build-up of fatty tissue called
plaque inside arteries that can impede or block
blood flow.
Carotid artery—One of the major blood vessels
leading to the brain; it runs up the front of the
neck.
Echocardiography—A type of ultrasonography that
is used to create an image of the heart and its
functioning.
Endarterectomy—A surgical procedure in which
diseased tissue and atherosclerotic plaque are
removed from the inside of an artery.
Ischemia—A condition in which blood flow is cut
off or restricted from a particular area. The surrounding tissue, starved of oxygen and nutrients,
dies.

PERIODICALS

Johnsen, Soren P., et al. ‘‘Intake of Fruit and Vegetables and
the Risk of Ischemic Stroke in a Cohort of Danish Men
and Women.’’ American Journal of Clinical Nutrition
July 2003: 57–58.
‘‘Reserachers Uncover the Brainós Stroke Protection
System.’’ Biotech Week October 29, 2003: 3.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave.
Dallas, TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Stroke Association. 9707 E. Easter Lane,
Englewood, Co. 80112. (800) 787-6537. <http://
www.stroke.org>.

Julia Barrett
Teresa G. Odle

Transplant reaction screening test
see Cytomegalovirus antibody screening
test
Transplantation see Corneal transplantation;
Hair transplantation; Heart
transplantation; Kidney transplantation;
Lung transplantation; Pancreas
transplantation

Microemboli—Small blot clots in the bloodstream.
Platelets—Tiny cells in the blood that help form
blood clots.
Stenosis—The narrowing of an opening or passageway in the body. In arteries, stenosis is caused by a
build-up of atherosclerotic plaque, disease, or
other disorder.
Stroke—A condition in which blood flow to the
brain has been blocked, thereby causing brain
cells to die from lack of oxygen and nutrients; also
called a ‘‘brain attack.’’
Ultrasonography—A medical test in which
sound waves are directed against internal structures in the body. As sound waves bounce off
the internal structure, they create an image on a
video screen.
Vertebrobasilar arteries—Major blood vessels that
lead to the brain. They are located at the base of the
skull at the back of the head.

3768

Transposition of the great
arteries
Definition
Transposition of the great arteries is a birth defect
causing a fatal condition in which there is a reversal, or
switch, in the truncal connections of the two main
(great) blood vessels to the heart, the aorta and pulmonary artery.

Description
There are two great arteries, the pulmonary artery
and the aorta. Normally, the pulmonary artery carries
blood from the right ventricle to the lungs. The aorta
carries blood from the left ventricle to the vessels of the
rest of the body.
Normally, blood returning to the heart is
depleted in oxygen. It goes first to the right atrium
of the heart and then to the right ventricle where it
is pumped to the lungs. While in the lungs, the
GALE ENCYCLOPEDIA OF MEDICINE

Transposition of the great arteries results in
oxygen-depleted blood going to the body. The reason is that the connection of the two great arteries
is reversed. In this case, the aorta is connected to
the right ventricle. Blood returning to the heart
goes to the right atrium and ventricle, which is
normal. Then, when the right ventricle pumps the
blood out, it goes into the aorta for distribution
throughout the body. At the same time, blood in
the lungs goes to the left atrium, the left ventricle,
but then back to the lungs. This happens because
the pulmonary artery is connected to the left ventricle. The result is that highly-oxygenated blood
keeps recycling through the lungs, while oxygendepleted blood recycles through the body without
going through the lungs to reoxygenate.
This condition develops during the fetal stage and
must be treated promptly after birth if the newborn is
to survive. The newborn can survive for a few days
because the foramen ovale, a small hole in the septum
that separates the two atria, is open, allowing some
oxygenated blood to escape and mix into the blood
that is being pumped throughout the body. However,
the foramen ovale normally closes within a few days
after birth.

Causes and symptoms
Transposition of the great arteries is a birth defect
that occurs during fetal development. There is no
identifiable disease or cause. The main symptom is a
‘‘blue’’ baby appearance, caused by a general lack of
oxygen in the body’s tissues.

Diagnosis
Diagnosis is made immediately after birth, when
it is observed that the newborn is lacking oxygen.
This is noted by the bluish color of the newborn,
indicating cyanosis, a lack of oxygen. A definite diagnosis is made by x ray, electrocardiography (ECG),
and echocardiography.

coronary arteries are also reconnected, so that they
can supply blood to the heart itself. A catheter may be
used to maintain or enlarge the opening between the
two atria until surgery can be performed.

Prognosis
Left untreated, this disease is fatal within the first
weeks of life.

Prevention
Because there is no identifiable cause, there is no
way to prevent this condition.
Resources
BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, editors.
TheHeart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD

Transsexualism see Gender identity disorder

Transurethral bladder
resection
Definition
Transurethral bladder resection is a surgical procedure, performed under sedation or anesthesia, with a
lighted tube inserted through the urethra (the small
tube-like structure that allows urine to empty from the
bladder), into the bladder. It plays both a diagnostic
and therapeutic role in the treatment of bladder
cancers.

Purpose
Tranurethral resection is the initial form of treatment for bladder cancers. The procedure is performed
to remove and examine bladder tissue and/or tumor. It
may also serve to remove lesions and be the only
treatment necessary for noninvasive tumors.

Description
Treatment
The only treatment for this condition is prompt
heart surgery shortly after birth. In surgery, the two
great arteries are reconnected to their proper destination. This restores the normal blood flow pattern. The
GALE ENCYCLOPEDIA OF MEDICINE

For this procedure, a lighted tube (resectoscope) is
inserted through the urethra, into the bladder. A clear
solution is infused to maintain visibility, and the
tumor or tissue to be examined is cut away using an
electric current. Tumor and muscle fibers are biopsied
3769

Transurethral bladder resection

blood picks up more oxygen. After the lungs, the
blood flows to the left atrium, then the left ventricle, which pumps the blood out through the
aorta to the rest of the body, thereby supplying
the body with oxygenated blood.

Transvaginal ultrasound

(a sample is cut out and examined, usually under a
microscope) in order to evaluate the depth of tissue
involvement, while avoiding perforation of the bladder wall. Every attempt is made to remove all visible
tumor tissue, along with a small border of healthy
tissue. The resected tissue is examined under the
microscope for diagnostic purposes. An indwelling
catheter may be inserted to ensure adequate drainage
of the bladder postoperatively. At this time, interstitial
radiation therapy may be initiated if necessary.

Preparation
Preoperative x rays with dye studies are helpful as
a guide in determining the character and extent of
tumor involved. As with any surgical procedure, the
patient is asked to sign a consent form after the procedure is thoroughly explained.

Aftercare
As with any surgical procedure, blood pressure and
pulse will be monitored. Urine is expected to be bloodtinged in the early postoperative period. Continuous
bladder irrigation (rinsing) may be used for approximately 24 hours after surgery. Most operative sites should
be completely healed in three months. The patient is
followed closely for possible recurrence with visual examination, using a special viewing device (cystoscope) at
regular intervals as the physician deems necessary.

Abnormal results
Complications of the procedure may include
bleeding, which may require bladder irrigation postoperatively, during which time the patient’s activity is
limited to bedrest. Perforation of the bladder is
another risk, in which case the urinary catheter is left
in place for four to five days postoperatively. The
patient is started on antibiotic therapy preventively.
If the bladder is lacerated, accompanied by spillage of
urine into the abdomen, an abdominal incision may be
required.
Resources
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.

Kathleen D. Wright, RN
3770

Transvaginal ultrasound
Definition
Transvaginal ultrasound is a imaging technique
used to create a picture of the genital tract in women.
The hand-held device that produces the ultrasound
waves is inserted directly into the vagina, close to the
pelvic structures, thus often producing a clearer and
less distorted image than obtained through transabdominal ultrasound technology, where the probe is
located externally on the skin of the abdomen.

Purpose
Transvaginal ultrasound can used to evaluate problems or abnormalities of the female genital tract. It
may provide more accurate information than transabdominal ultrasound for women who are obese, for
women who are being evaluated or treated for infertility, or for women who have difficulty keeping a full
bladder. However, it does provide a view of a smaller
area than the transabdominal ultrasound. Types of
conditions or abnormalities that can be examined
include:


the endometrium of women with infertility problems
or who are experiencing abnormal bleeding



sources of unexplained pain



congenital malformations of the ovaries and uterus



ovarian cysts and tumors



pelvic infections, such as pelvic inflammatory
disease



bladder abnormalities



a misplaced IUD (intrauterine device)



other causes of infertility

Transvaginal ultrasound can also be used during
pregnancy. Its capability of producing more complete
images means that it is especially useful for identifying
ectopic pregnancy, fetal heartbeat, and abnormalities of the uterus, placenta, and associated pelvic
structures.
Transvaginal ultrasound is performed by an ultrasound technologist, who is supervised by a radiologist
or a specialist such as an obstetrician.

Precautions
Studies have shown that ultrasound is not hazardous and has no harmful side effects.
GALE ENCYCLOPEDIA OF MEDICINE

A ultrasound, or sonogram, is a procedure that
utilizes reflected sound waves to produce a picture of
organs and structures within the body. A transducer
sends out high-pitched sounds, sounds that are above
the range of human hearing, that are reflected back to
the transducer. A computer is used to analyze the
sound waves, transforming them into a picture
(which is called a sonogram, echogram, or ultrasound
scan) on a video monitor. These pictures can be saved
as a permanent record of the test.
A transvaginal ultrasound is used for looking at
organs and structures within the pelvic area that are
solid and uniform, like the uterus, and ovaries, or for
organs that are fluid-filled, like the bladder.
Mineralized structures, like bones, or air-filled organs,
such as the intestines, do not show up well on a sonogram and may disrupt the ultrasound beam so that
deeper organs and structures cannot be seen clearly.
The transvaginal transducer that produces the
ultrasound waves is shaped to fit within a woman’s
vagina. It is lubricated and covered with a sheath such
as a condom. A woman should tell the health care
provider if she is allergic to latex so that a latex-free
cover can be applied to the transducer before it is
inserted into the vagina.
Sometimes a woman may have both transvaginal
and transabdominal ultrasound scans done to obtain a
complete evaluation of the pelvic area.

Preparation
There is no special preparation required by a
woman before a transvaginal ultrasound. She can continue to take medications prescribed by her health care
provider, although she should not drink liquids for four
hours before the test. A full bladder is not required for a
transvaginal ultrasound, as is required for a transabdominal ultrasound. The test can be administered during any stage of the woman’s menstrual cycle.
During the procedure, the woman lies on her
back, with her hips slightly raised. The thin, lubricated
tip of the transducer is inserted gently into the vagina.
The transducer is moved and rotated to adjust the view
of the pelvic structures displayed on the monitor. The
woman must lie very still during the ultrasound scan.
She may feel a mild discomfort from the pressure of
the vaginal transducer. The procedure usually takes
from 15 to 30 minutes.
Occasionally, hysterosonography is done on a nonpregnant woman to evaluate the inside of the uterus
GALE ENCYCLOPEDIA OF MEDICINE

(endometrial cavity) and fallopian tubes by filling the
uterus with fluid during a transvaginal ultrasound.

Aftercare
There is a slight risk of infection associated with a
transvaginal ultrasound, especially if a biopsy was done
in conjunction with the procedure. Therefore the patient
should be aware of symptoms of an infection and seek
care from a health care professional as necessary.

Risks
Since no ionizing radiation is associated with
transvaginal ultrasound, there has been no documented adverse effects on patients or their fetuses with the
use of the procedure.

Normal results
In a normal transvaginal ultrasound, the pelvic
structures or organs or the fetus are found to have no
abnormalities.

Abnormal results
Abnormal ultrasound results can be due to a variety of conditions and diseases. In non-pregnant
women, these abnormal results may include:


cancerous tumors or non-cancerous growths of the
uterus, ovaries, vagina, or other pelvic structures



ovarian torsion



infections such as PID



congenital malformations.

In pregnant women, the following abnormalities
may be diagnosed through transvaginal ultrasound:


ectopic pregnancies



multiple pregnancies



fetal death



short cervix length, which may indicate the risk of
preterm labor



placental abnormalities such as placental previa and
placental abruption



tumors of pregnancy, including gestational trophoblastic disease.

A biopsy is needed to determine whether a tumor
that is found during the transvaginal ultrasound scan
is cancerous or non-cancerous.
3771

Transvaginal ultrasound

Description

Transverse myelitis

ORGANIZATION

KEY TERMS
Ectopic pregnancy—Pregnancy that develops outside the uterus, usually in one of the fallopian tubes
Endometrium—The mucous membrane that makes
up the inner layer of the uterine wall
Gestational trophoblastic disease—A rare, aggressive, malignant, often metastatic (spreading to other
organs) cancer in women of childbearing age in
which cancer cells grow in the tissues that are
formed in the uterus after conception
Intrauterine device (IUD)—Contraceptive device
consisting of a piece of bent plastic or metal that is
inserted through the vagina into the uterus
Transabdominal ultrasound—A small handheld
instrument called a transducer is passed back and
forth over the pelvic area to provide images of the
abdomen
Ovarian torsion—Twisting of the ovary due to the
influence of another condition or disease, resulting
in extreme lower abdominal pain
Pelvic inflammatory disease (PID)—Inflammation
of the female genital tract, especially of the fallopian tubes, caused by any of several microorganisms, chiefly chlamydia and gonococci, and
characterized by severe abdominal pain, high
fever, vaginal discharge, and in some cases destruction of tissue that can result in sterility
Placental abruption—Premature separation of the
placenta from the uterus
Placenta previa—A low-lying placenta that covers
part or all of the inner opening of the cervix. This
can result in heavy bleeding during labor and
delivery, which can be dangerous for mother and
baby.

Resources
BOOKS

Dodson, Melvin G.Transvaginal Ultrasound.Philadelphia:
W.B Saunders and Company, 1995.
Smith, Norman C., and Smith, Pat M.Obstetric Ultrasound
Make Easy.London: Churchill Livingstone, 2001.
PERIODICALS

Singh, K., and Malhotra, N.Step-by-Step Ultrasound in
Gynecology.New York: McGraw Hill Companies,
2004.
Singh, K., and Malhotra, N.Step-by-Step Ultrasound in
Infertility.New York: McGraw Hill Companies, 2004.
3772

The American Institute of Ultrasound in Medicine, 14750
Sweitzer Lane, Suite 100, Laurel, MD 20707.
Telephone: 301-498-4100. Web site: www.aium.org/

Judith L. Sims

Transverse myelitis
Definition
Transverse myelitis (TM) is an uncommon neurological syndrome caused by inflammation (a protective response which includes swelling, pain, heat, and
redness) of the spinal cord, characterized by weakness,
back pain, and bowel and bladder problems. It affects
one to five persons per million.

Description
TM affects the entire thickness of the spinal cord,
producing both sensory and movement problems. It is
believed to be linked to the immune system, which may
be prompted to attack the body’s own spinal cord.
Striking rapidly without warning, its effects can be
devastating.

Causes and symptoms
Transverse myelitis has many different causes,
often triggered by a variety of viral and bacterial infections (especially those associated with a rash such as
measles or chickenpox). Once the infection subsides,
the inflammation in the cord begins. About a third of
patients experience a flu-like illness with fever about
the time they develop symptoms of TM. Sometimes,
there appears to be a direct invasion of, and injury to,
the spinal cord by an infectious agent (such as herpes
zoster or the AIDS virus).
TM can also accompany a variety of diseases that
break down tissue that surrounds and insulates the
nerves (demyelinating diseases), such as multiple
sclerosis (MS).
Some toxic substances, such as carbon monoxide,
lead, or arsenic, can cause a type of myelitis characterized by inflammation followed by hemorrhage or
bleeding that destroys the entire circumference of the
spinal cord. Other types of myelitis can be caused by
poliovirus; herpes zoster; rabies, smallpox or polio
vaccination; or parasitic and fungal infections.
GALE ENCYCLOPEDIA OF MEDICINE

Regardless of the cause of the myelitis, onset of
symptoms is sudden and rapid. Problems with movement and sensation appear within one or two days
after inflammation begins. Symptoms include soft
(flaccid) paralysis of the legs, with pain in the lower
legs or back, followed by loss of feeling and sphincter
(muscles which close an opening, as in the anus) control. The earliest symptom may be a girdle-like sensation around the trunk.
The extent of damage occuring will depend on
how much of the spinal cord is affected, but TM rarely
involves the arms. Severe spinal cord damage also can
lead to shock.

Diagnosis
A doctor will suspect transverse myelitis in any
patient with a rapid onset of paralysis. Medical history, physical examination, brain and spinal cord
scans, myelogram, spinal tap, and blood tests are
used to rule out other neurological causes of symptoms, such as a tumor. If none of these tests suggest a
cause for the symptoms, the patient is presumed to
have transverse myelitis.

KEY TERMS
Demyelinating disorders—A group of diseases
characterized by the breakdown of myelin, the
fatty sheath surrounding and insulating nerve
fibers. This breakdown interferes with nerve function, and can result in paralysis. Multiple sclerosis
is a demyelinating disorder.
Myelogram—An x-ray examination of the brain
and spinal cord with the aid of a contrast dye, to
look for tumors or spinal cord injury.

how to cope with activities of daily living. People who
develop spastic reflexes early in the course of the condition are more likely to recover than those who do
not. If spinal cord tissue death (necrosis) occurs, the
chance of a complete recovery is poor. Most recovery
occurs within the first three months. A certain percentage of patients with TM will go on to develop multiple
sclerosis.
Resources
ORGANIZATIONS

Transverse Myelitis Association. 1787 Sutter Parkway,
Powell, OH 43065-8806. (614) 766-1806. <http://
www.myelitis.org>.

Carol A. Turkington

Treatment
There is no effective treatment for transverse myelitis, but any underlying infection must be treated.
After this, the focus of care shifts from diagnosis and
treatment to learning how to live with the effects of the
syndrome. Patients are helped to cope psychologically
with new limitations, and are given physical
rehabilitation.
Physical adaptations include learning to cope with
bowel and bladder control, sexuality, inability to control muscles (spasticity), mobility, pain, and activities
of daily living (such as dressing).
As nerve impulses from the spinal cord are often
scrambled and misinterpreted by the brain as pain, painkillers are given to ease discomfort. Antidepressants or
anticonvulsants may also help.

Prognosis
The prognosis depends on how much of the cord
was damaged. Some people recover completely, while
others have lasting problems and need help in learning
GALE ENCYCLOPEDIA OF MEDICINE

Tranylcypromine see Monoamine oxidase
inhibitors

Traumatic amputations
Definition
Traumatic amputation is the accidental severing of
some or all of a body part. A complete amputation
totally detaches a limb or appendage from the rest of
the body. In a partial amputation, some soft tissue
remains attached to the site.

Description
Trauma is the second leading cause of amputation
in the United States. About 30,000 traumatic amputations occur in this country every year. Four of every
3773

Traumatic amputations

Many experts believe that TM can occur without
any apparent cause, probably as the result of an autoimmune process. This means that a person’s immune
system attacks the spinal cord, causing inflammation
and tissue damage.

Traumatic amputations

five traumatic amputation victims are male, and most
of them are between the ages of 15–30.
Traumatic amputation most often affects limbs
and appendages like the arms, ears, feet, fingers,
hands, legs, and nose.

Causes and symptoms
Farm and factory workers have greater-thanaverage risks of suffering injuries that result in
traumatic amputation. Automobile and motorcycle
accidents and the use of lawnmowers, saws, and
power tools are also common causes of traumatic
amputation.
Blood loss may be massive or minimal, depending
on the nature of the injury and the site of the amputation. Patients who lose little blood and have less severe
injuries sometimes feel more pain than patients who
bleed heavily and whose injuries are life-threatening.

Diagnosis
When the patient and the amputated part(s) reach
the hospital, an Emergency Department physician will
assess the probability that the severed tissue can be
successfully reattached.
The Mangled Extremity Severity Score (MESS)
assigns numerical values to such factors as body temperature, circulation, numbness, paralysis, tissue
health, and the patient’s age and general health. This
is one of the diagnostic tools used to determine how
successful reattachment surgery is apt to be. The total
score is doubled if blood supply to the amputated part
has been absent or diminished for more than six hours.
A general, emergency, or orthopedic surgeon
makes the final determination about whether surgery
should be performed. The surgeon also considers the
patient’s wishes and lifestyle. Additional concerns are
how and to what extent the amputation will affect the
patient’s quality of life and ability to perform everyday
activities.

This man’s hand was surgically reattached following a
traumatic amputation. (Photograph by Michael English, M.D.,
Custom Medical Stock Photo. Reproduced by permission.)

not been preserved will not survive for more than six
hours.
Initial response
The most important steps to take when a traumatic amputation occurs are:


Contact the nearest emergency services provider,
clearly describe what has happened, and follow any
instructions given.



Make sure the victim can breathe; administer CPR if
necessary.



Control bleeding, using direct pressure but minimizing or avoiding contact with blood and other body
fluids.



Patients should not be moved if back, head, leg, or
neck injuries are suspected or if motion causes pain.
If none are found by the EMT, lie the victim flat, with
the feet raised 12 inches above the surface.



Cover the victim with a coat or blanket to prevent
shock.

Treatment
First aid or emergency care given immediately
after the amputation has a critical impact on both
the physicians’ ability to salvage and reattach the severed part(s) and the patient’s ability to regain feeling
and function.
Muscle tissue dies quickly, but a well-preserved
part can be successfully reattached as much as 24
hours after the amputation occurs. Tissue that has
3774

The injured site should be cleansed with a sterile
solution and wrapped in a clean towel or other thick
material that will protect the wound from further
injury. Tissue that is still attached to the body should
not be forced back into place. If it cannot be gently
replaced, it should be held in its normal position and
supported until additional care is available.
GALE ENCYCLOPEDIA OF MEDICINE

Phantom pain—Pain, tingling, itching, or numbness in the place where the amputated part used
to be.

Saving the patient’s life is always more important than recovering the amputated part(s).
Transporting the patient to a hospital or emergency
center should never be delayed until missing pieces
are located.
Preserving tissue
No amputated body part is too small to be salvaged. Debris or other contaminating material should
be removed, but the tissue should not be allowed to
get wet.
An amputated body part should be wrapped in
bandages, towels, or other clean, protective material
and sealed in a plastic bag. Placing the sealed bag in a
cooler or in a container that is inside a second container filled with cold water or ice will help prevent
tissue deterioration.



last for a few minutes or several hours



help patients adjust more readily to an artificial limb
(prosthesis).

Prevention
The best way to prevent traumatic amputation is
to observe common-sense precautions like using seat
belts and obeying speed limits and other traffic regulations. It is important to take special precautions when
using potentially dangerous equipment and make sure
machinery is turned off and disconnected before
attempting to service or repair it. Appropriate protective clothing should be worn at all times.
Resources
ORGANIZATIONS

American Amputation Foundation, Inc. P.O. Box 250218,
Hillcrest Station, Little Rock, AR 72225. (501)
666-2523.
Amputee Coalition of America. P.O. Box 2528, Knoxville,
TN 37901-2528. (888) 267-5669. <http://www
.amputee-coalition.org>.

Maureen Haggerty

Prognosis
Possible complications of traumatic amputation
include:


excessive bleeding



infection



muscle shortening



pulmonary embolism.

Improved medical and surgical care and rehabilitation have improved the long-term outlook for these
patients.
Phantom pain
About 80% of all amputees over the age of four
experience tingling, itching, numbness, or pain in the
place where the amputated part used to be. Phantom
sensations may begin immediately after the amputation, or they may develop months or years later.
They often occur after an injury to the site of the
amputation.
These intermittent feelings may:


occur frequently or only once in a while



be mild or intense

GALE ENCYCLOPEDIA OF MEDICINE

Traveler’s diarrhea
Definition
The occurrence of multiple loose bowel movements in someone traveling to an area outside their
usual surroundings (usually from temperate industrialized regions to tropical areas), is known as Traveler’s
diarrhea (TD). The cause is almost always due to a
bacterial or viral infection acquired through ingesting
contaminated food or water.

Description
It is estimated that anywhere from 20–50% of the
12–20 million travelers going from temperate industrialized countries to the tropics will develop TD.
Fortunately, most of these episodes are of short duration. Nevertheless, about 40% of those affected will
need to rearrange their schedule, and 20% will be ill
enough to remain in bed for some days.
The chance of winding up with TD is directly
related to the area one is traveling to; only about 8%
of individuals visiting an industrialized country are
affected, whereas at least half of those traveling to
3775

Traveler’s diarrhea

KEY TERMS

Traveler’s diarrhea

non-industrialized regions become ill. It is also clearly
related to the number of potentially contaminated
foods or beverages consumed. Attention to recommended guidelines regarding food safety and sanitation can greatly decrease the risk of infection.

Causes and symptoms
Bacterial infections are the most common cause of
the illness. Viruses and occasional parasites also can be
the cause. As for the bacteria involved, toxin producing types of E. coli (called enterotoxigenic) account for
approximately 40–60% of cases, with Campylobacter
and Shigella each reported in at least 10% of cases. In
some studies, Campylobacter has accounted for almost
half of the attacks, especially during cooler seasons of
the year. The cause can vary depending on several
factors, including the season and country visited.
More than one organism can be found in 15–30% of
cases, while none is identified in up to 40% of cases
worldwide.
Rotaviruses and a parvovirus called Norwalk
agent also are responsible for TD. Giardia is probably
the most common parasite identified, though amoebas
(Entamoeba histolytica), Cryptosporidium, and
Cyclospora are being found with increasing frequency.
Amazingly, research released in 2003 found that those
living in undeveloped countries with poor sanitation
and high incidence of diarrheal disease also have the
lowest incidence of colorectal cancer. It appears that
an enterotoxin secreted from multiple bacteria leads to
colon cancer resistance.
Younger age groups, particularly students, are at
greatest risk, probably because of where and what they
eat. Individuals over 55 years of age, persons staying
with relatives, or business travelers are at lower risk.
Foods with the highest chance of transmitting disease
are uncooked vegetables, unpeeled fruits, meat, and
seafood. Tap water and even ice can be dangerous
unless one is sure of the source.
Symptoms usually start within a few days after
arrival, but can be delayed for as long as two weeks.
Illness lasts an average of 3 to 5 days, but is sometimes
longer. Cramping abdominal pain, lack of appetite,
and diarrhea are the main complaints. In approximately 10% of patients, diarrhea turns bloody. Fever
develops in about half of them. The presence of bloody
bowel movements and fever usually indicates a more
severe form of illness and makes Shigella a more likely
cause. Medications that decrease the motility or contractions of the intestine, such as loperamide
(Imodium) or diphenoxylate (Lomotil), should not
be used when fever or bleeding occur.
3776

Complications
Diarrhea varies from a few loose stools per day to 10
or more. Dehydration and changes in the normal blood
pH (acid-base balance) are the main dangers associated
with TD. Signs of dehydration can be hard to notice, but
increasing thirst, dry mouth, weakness or lightheadedness (particularly if worsening while standing), or a darkening/decrease in urination are suggestive. Severe
dehydration and changes in the body’s chemistry can
lead to kidney failure and become life-threatening.
Another potential complication is ‘‘toxic megacolon,’’ in which the colon gradually stretches and its
wall thins to the point where it can tear. The presence
of a hole in the intestine leads to peritonitis and is fatal
unless quickly recognized and treated.
Other complications related to TD can involve the
nervous system, skin, blood, or kidneys.

Diagnosis
The occurrence of diarrhea in an individual while
traveling is very suggestive of TD. Although there are
other possible causes, these are less likely. In most
instances, the specific organism responsible for the
symptoms does not need to be identified, and the
majority of patients need only rest and treatment to
avoid potential complications.
When patients develop fever or bloody diarrhea,
the illness is more serious and a specific diagnosis is
needed. In those cases, or when symptoms last longer
than expected, stool samples are obtained to identify
the organism.
For this purpose, laboratories can either try to
grow (culture) the organism, or identify it with highpowered microscopes (electron microscopy) or with
the use of special tests or stains. These can show parasites such as Giardia, Amoeba, Cryptosporidium and
others in freshly obtained stool specimens. New techniques that involve identification of DNA (the characteristic material that controls reproduction and is
unique for all individuals) of the various organisms,
also can be used in special circumstances.

Treatment
The best treatment of TD is prevention; however,
once disease occurs, therapy is aimed at preventing or
reducing dehydration, and using antibiotics when
needed. Fortunately, severe dehydration is unusual
in patients with TD, but any fluid losses should be
treated early with either fruit juices and ‘‘clear fluids’’
such as tea or broth, or with the recommended Oral
GALE ENCYCLOPEDIA OF MEDICINE

When nothing else is available, the following
WHO recipe can be made up from household items
and taken in small frequent sips;


table salt: 1-3/4 teaspoon



baking powder: 1 teaspoon



orange juice: 1 cup



water: 1 quart or liter

A debate has occurred in the medical community
over the amount of salt (sodium) in the WHO preparations; some physicians feel that the content is too much
for use by well-nourished persons in developed countries.
Therefore these preparations should not be used for
extended periods of time without consulting a physician.
Pepto-Bismol (bismuth subsalicylate preparation)
is effective in both preventing and treating TD. For
treatment once symptoms begin, the drug must be
taken more frequently than when used for prevention.
Bismuth subsalicylate preparation (1 oz of liquid or two
262.5-mg tablets every 30 minutes for eight doses) has
been shown to decrease the number of bowel movements and shorten the length of illness. However, there
is some concern about the large doses of bismuth in
patients with kidney disease; therefore patients should
check with physicians before starting this or any other
therapy. Patients should be aware that bismuth can
turn bowel movements black in color.
In 2003, a new drug called rifamixin (Normix) for
treating traveler’s diarrhea was nearing approval by
the U.S. Food and Drug Administration (FDA).
Medications designed to decrease intestinal motility
and contractions such as loperamide (Imodium),
diphenoxylate (Lomotil), or others are safest when
used by those without fever or bloody bowel movements. The presence of either of these symptoms indicates a more severe form of colitis.
Antibiotics are usually not prescribed, because
most cases of TD rapidly improve with minimal treatment. For patients in whom symptoms are especially
severe (4 or more stools per day or the onset of bloody
diarrhea or fever), or those with compromised immune
systems, antibiotics are indicated. Individuals with less
severe attacks can be treated with either antimotility
medications or bismuth subsalicylate.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Oral Rehydration Solution (ORS)—A liquid
preparation developed by the World Health
Organization that can decrease fluid loss in persons
with diarrhea. Originally developed to be prepared
with materials available in the home, commercial
preparations have recently come into use.

Choice of an antibiotic should ideally be tailored
to the most likely organism and then adjusted according to results of stool cultures. Trimethoprimsulfamethoxazole (Bactrim) or ciprofloxacin (Cipro)
are the antibiotics most often prescribed, but others
are also used. The type and duration of treatment
continues to be revised, and it is therefore extremely
important that patients check with a physician prior to
beginning treatment. In many instances, an antibiotic
can be combined with an anti-motility agent to provide the quickest relief.

Prognosis
Up to 1% of patients with TD will become sick
enough to require hospitalization, and 3% will continue
to experience diarrhea for at least one month. The majority of patients rapidly recover with minimal therapy.
Some will suffer symptoms for even longer. The small
number who continue to suffer symptoms will need careful evaluation to rule out the many causes of chronic
diarrhea (such as lactase deficiency, irritable bowel syndrome, parasites, etc.). It is unusual for diarrhea caused
by bacteria to last over two weeks; therefore, more prolonged diarrhea indicates a non-bacterial cause.

Prevention
The best means of prevention is avoiding foods,
beverages, and food handling practices that lead to
infection with the organisms that cause TD. Drinking
bottled water and using bottled water for brushing teeth,
eating fruits that the traveler peels on his or her own, and
eating well-cooked, hot foods can help prevent illness.
One effective means to prevent TD is liquid PeptoBismol; this bismuth-containing compound has been
shown to be very effective in reducing the incidence of
TD. Tablets are now available, which are easier to
carry. Two tablets four times a day is recommended,
but use should not go beyond three weeks.
Antibiotics can also prevent TD, but their use is
controversial, unless it is absolutely necessary to avoid
3777

Traveler’s diarrhea

Rehydration Solutions (ORS) suggested by the World
Health Organization (WHO). Persons traveling to
known areas of infection should consult with their
physician prior to departure and obtain appropriate
instructions. For example, it may be advised to take
along pre-prepared packets of ORS designed for easy
mixing or commercial preparations such as Pedialyte,
Ceralyte, Ricelyte, etc.

Tremors

infection (such as someone on an important business
trip or who has a weakened immune system). There is
the tendency for bacteria to become resistant to these
medications if used excessively; and these drugs have
side effects that can be worse than the effects of TD.
The benefits and risks of antibiotic treatment should
be carefully weighed.
Resources
PERIODICALS

Jenkins, Susan. ‘‘Ah, the Irony: Colon Cancer Resistance
Found in Travelerós Diarrhea.’’ The Scientist March
24, 2003: 27.
‘‘Rifamixin for Travelerós Diarrhea.’’ R & D Directions
January 2003: 60.
Seale, J. Paul. ‘‘Travel Risks: Update on Travelerós
Diarrhea and Other Common Problems.’’ Consultant
December 2002: 1778.

Underlying disease
Some types of tremor are signs of an underlying
condition. About a million and a half Americans have
Parkinson’s disease, a disease that destroys nerve cells.
Severe shaking is the most apparent symptom of
Parkinson’s disease. This coarse tremor features four
to five muscle movements per second. The shaking is
evident at rest but declines or disappears during
movement.
Other disorders that cause tremor are multiple
sclerosis, Wilson’s disease, mercury poisoning, thyrotoxicosis, and liver encephalopathy.
A tremor that gets worse during body movement
is called an ‘‘intention tremor.’’ This type of tremor is a
sign that something is amiss in the cerebellum, a region
of the brain concerned chiefly with movement, balance
and coordination.

OTHER

Centers for Disease Control. <http://www.cdc.gov/
nccdphp/ddt/ddthome.htm>.

David Kaminstein, MD
Teresa G. Odle

Tremors
Definition
Tremor is an unintentional (involuntary), rhythmical alternating movement that may affect the muscles of any part of the body. Tremor is caused by the
rapid alternating contraction and relaxation of muscles and is a common symptom of diseases of the
nervous system (neurologic disease).

Description
Occasional tremor is felt by almost everyone,
usually as a result of fear or excitement. However,
uncontrollable tremor or shaking is a common symptom of disorders that destroy nerve tissue, such as
Parkinson’s disease or multiple sclerosis. Tremor
may also occur after stroke or head injury. Other
tremors appear without any underlying illness.

Causes and symptoms
Tremor may be a symptom of an underlying disease, and it may be caused by drugs. It may also exist
as the only symptom (essential tremor).
3778

Essential tremor
Many people have what is called ‘‘essential tremor,’’ in which the tremor is the only symptom. This
type of shaking affects between three and four million
Americans.
The cause of essential tremor is not known,
although it is an inherited problem in more than half
of all cases. The genetic condition has an autosomal
dominant inheritance pattern, which means that any
child of an affected parent will have a 50% chance of
developing the condition.
Essential tremor most often appears when the
hands are being used, whereas a person with
Parkinson’s disease will most often have a tremor
while walking or while the hands are resting. People
with essential tremor will usually have shaking head
and hands, but the tremor may involve other parts of
the body. The shaking often begins in the dominant
hand and may spread to the other hand, interfering
with eating and writing. Some people also develop a
quavering voice.
Essential tremor affects men and women equally.
The shaking often appears at about age 45, although
the disorder may actually begin in adolescence or early
adulthood. Essential tremor that begins very late in
life is sometimes called ‘‘senile tremor.’’
Drugs and tremor
Several different classes of drugs can cause tremor
as a side effect. These drugs include amphetamines,
antidepressant drugs, antipsychotic drugs, caffeine, and
lithium. Tremor also may be a sign of withdrawal from
alcohol or street drugs.
GALE ENCYCLOPEDIA OF MEDICINE

Close attention to where and how the tremor
appears can help provide a correct diagnosis of the
cause of the shaking. The source of the tremor can be
diagnosed when the underlying condition is found.
Diagnostic techniques that make images of the brain,
such as computed tomography scan (CT scan) or
magnetic resonance imaging (MRI), may help form a
diagnosis of multiple sclerosis or other tremor caused
by disorders of the central nervous system. Blood tests
can rule out such metabolic causes as thyroid disease.
A family history can help determine whether the tremor is inherited.

Treatment
Neither tremor nor most of its underlying causes
can be cured. Most people with essential tremor
respond to drug treatment, which may include propranolol, primidone, or a benzodiazepine. People with
Parkinson’s disease may respond to levodopa or
other antiparkinson drugs.
Research has shown that about 70% of patients
treated with botulinum toxin A (Botox) have some
improvement in tremor of the head, hand, and voice.
Botulinum is derived from the bacterium Clostridium
botulinum. This bacterium causes botulism, a form of
food poisoning. It is poisonous because it weakens
muscles. A very weak solution of the toxin is used in
cases of tremor and paralysis to force the muscles to
relax. However, some patients experience unpleasant
side effects with this drug and cannot tolerate effective
doses. For other patients, the drug becomes less effective over time. About half of patients don’t get any
relief of tremor from medications.
Tremor control therapy
Tremor control therapy is a type of treatment
using mild electrical pulses to stimulate the brain.
These pulses block the brain signals that trigger tremor. In this technique, the surgeon implants an electrode into a large oval area of gray matter within the
brain that acts as a relay center for nerve impulses and
is involved in generating movement (thalamus). The
electrode is attached to an insulated wire that runs
through the brain and exits the skull where it is
attached to an extension wire. The extension is connected to a generator similar to a heart pacemaker.
The generator is implanted under the skin in the chest,
and the extension is tunneled under the skin from the
skull to the generator. The patient can control his or
GALE ENCYCLOPEDIA OF MEDICINE

her tremor by turning the generator on with a handheld magnet to deliver an electronic pulse to the brain.
Some patients experience complete relief with this
technique, but for others it is of no benefit at all.
About 5% of patients experience complications from
the surgical procedure, including bleeding in the brain.
The procedure causes some discomfort, because
patients must be awake while the implant is placed.
Batteries must be replaced by surgical procedure every
three to five years.
Other surgical treatments
A patient with extremely disabling tremor may
find relief with a surgical technique called thalamotomy, in which the surgeon destroys part of the thalamus. However, the procedure is complicated by
numbness, balance problems, or speech problems in a
significant number of cases.
Pallidotomy is another type of surgical procedure sometimes used to decrease tremors from
Parkinson’s disease. In this technique, the surgeon
destroys part of a small structure within the brain
called the globus pallidus internus. The globus is
part of the basal ganglia, another part of the brain
that helps control movement. This surgical technique
also carries the risk of disabling permanent side
effects.
Fetal tissue transplantation (also called a nigral
implant) is a controversial experimental method to
treat Parkinson’s disease symptoms. This method
implants fetal brain tissue into the patient’s brain to
replace malfunctioning nerves. Unresolved issues
include how to harvest the fetal tissue and the moral
implications behind using such tissue, the danger of
tissue rejection, and how much tissue may be required.
Although initial studies using this technique looked
promising, there has been difficulty in consistently
reproducing positive results.
Small amounts of alcohol may temporarily (sometimes dramatically) ease the shaking. Some experts
recommend a small amount of alcohol (especially
before dinner). The possible benefits, of course, must
be weighed against the risks of alcohol abuse.

Prognosis
Essential tremor and the tremor caused by neurologic disease (including Parkinson’s disease)
slowly get worse and can interfere with a person’s
daily life. While the condition is not life3779

Tremors

Diagnosis

Tremors

KEY TERMS
Computed tomography (CT) scan—An imaging
technique in which cross-sectional x rays of the
body are compiled to create a three-dimensional
image of the body’s internal structures.
Essential tremor—An uncontrollable (involuntary)
shaking of the hands, head, and face. Also called
familial tremor because it is sometimes inherited; it
can begin in the teens or in middle age. The exact
cause is not known.
Fetal tissue transplantation—A method of treating
Parkinson’s and other neurological diseases by grafting brain cells from human fetuses onto the affected
area of the human brain. Human adults cannot grow
new brain cells but developing fetuses can. Grafting
fetal tissue stimulates the growth of new brain cells in
affected adult brains.
Intention tremor—A rhythmic purposeless shaking
of the muscles that begins with purposeful (voluntary) movement. This tremor does not affect muscles
that are resting.
Liver encephalopathy—A condition in which the
brain is affected by a buildup of toxic substances
that would normally be removed by the liver. The
condition occurs when the liver is too severely
damaged to cleanse the blood effectively.
Multiple sclerosis—A degenerative nervous system
disorder in which the protective covering of the
nerves in the brain are damaged, leading to tremor
and paralysis.

control of willed (voluntary) movement of the
muscles.
Parkinson’s disease—A slowly progressive disease
that destroys nerve cells. Parkinson’s is characterized by shaking in resting muscles, a stooping posture, slurred speech, muscular stiffness, and
weakness.
Thalamotomy—A surgical procedure that destroys
part of a large oval area of gray matter within the
brain that acts as a relay center for nerve impulses.
The thalamus is an essential part of the nerve pathway that controls intentional movement. By destroying tissue at a particular spot on the thalamus, the
surgeon can interrupt the nerve signals that cause
tremor.
Thalamus—A large oval area of gray matter within
the brain that relays nerve impulses from the basal
ganglia to the cerebellum, both parts of the brain that
control and regulate muscle movement.
Thyrotoxicosis—An excess of thyroid hormones in
the blood, causing a variety of symptoms that
include rapid heart beat, sweating, anxiety, and
tremor.

Pallidotomy—A surgical procedure that destroys a
small part of a tiny structure within the brain called
the globus pallidus internus. This structure is part of
the basal ganglia, a part of the brain involved in the

Tremor control therapy—A method for controlling
tremor by self-administered shocks to the part of the
brain that controls intentional movement (thalamus).
An electrode attached to an insulated lead wire is
implanted in the brain; the battery power source is
implanted under the skin of the chest, and an extension wire is tunneled under the skin to connect the
battery to the lead. The patient turns on the power
source to deliver the electrical impulse and interrupt
the tremor.
Wilson’s disease—An inborn defect of copper metabolism in which free copper may be deposited in a
variety of areas of the body. Deposits in the brain can
cause tremor and other symptoms of Parkinson’s
disease.

threatening, it can severely disrupt a person’s
everyday experiences.

amphetamines can prevent tremor that occurs as a side
effect of drug use.

Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.

Prevention
Essential tremor and tremor caused by a disease of
the central nervous system cannot be prevented.
Avoiding use of stimulant drugs such as caffeine and
3780

Resources
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave.,
St. Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.
GALE ENCYCLOPEDIA OF MEDICINE

Carol A. Turkington

Trench fever
Definition
Trench fever is a bacterial infection that causes
repeated cycles of high fever.

nickname ‘‘shin bone fever.’’ The fever can reach
1058F (40.58C) and stays high for five to six days at a
time. The temperature then drops, and stays down for
several days, usually recurring in five- to six-day cycles.
An individual may experience as many as eight cycles of
fever with the illness.

Diagnosis
Diagnosis is usually made on the basis of the
patient’s symptoms, and on knowledge of the conditions in which the patient lives. A blood sample can be
drawn and bacteria in the sample are allowed to grow.
Identification is made by looking at the number of
bacteria that may be present on a glass slide seen
under the lens of a microscope. However, this technique can take up to four weeks, because this type of
bacterium grows very slowly. By this time, the practitioner has often decided to treat the patient anyway.

Treatment
Description
The term trench fever refers to the crowded
conditions in which troops fought in during
World War I and World War II. Because the causative bacteria are passed among humans through
contact with body lice, overcrowding, and conditions which interfere with good hygiene (including
regular washing of clothing) soldiers were predispose to this disease. Currently, homeless people in
the United States are sometimes diagnosed with
this illness. The bacteria are sometimes passed
through the bite of an infected tick. This can
cause the illness in people who participate in outdoor activity and encounter ticks in that particular
area.

Causes and symptoms
Two different bacteria can cause trench fever:
Bartonella quintana and Bartonella henselae.B. quintana
is carried by body lice; B. henselae is carried by ticks.
Infection with B. quintana occurs when an infected
louse defecates while feeding on a human. When the
person scratches, the feces (which are full of bacteria)
are rubbed into the tiny wound. Infection with B. henselae
occurs when an infected tick bites a human, passing the
bacteria along through the tiny bite wound.
Symptoms of trench fever begin about 2 weeks to
a month after exposure to the bacteria. Sudden fever,
loss of energy, dizziness, headache, weight loss, skin
rash, severe muscle and bone pain can occur. Pain is
particularly severe in the shins, leading to the
GALE ENCYCLOPEDIA OF MEDICINE

Erythromycin and azithromycin are both used to
treat trench fever. Four weeks of treatment are usually
necessary. Inadequate treatment often results in a
relapse. In fact, relapses have been reported to occur
as long as 10 years after the first episode.

Prognosis
Prognosis for patients with trench fever is excellent. Recovery may take a couple of months. Without
treatment, there is always a risk of recurrence, even
years after the original illness.

Prevention
Prevention involves good hygiene and decent living conditions. When this is impossible, insecticide
dusting powders are available to apply to clothing.
Avoidance of areas known to harbor ticks or the use
of insect repellents is necessary to avoid the type of
infection passed by ticks.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Treponema carateum infection see Pinta
Treponema pallidum infection see Syphilis
3781

Trench fever

American Parkinson Disease Association. 60 Bay Street,
Suite 401, Staten Island, NY 10301. (800) 223-2732.
<http://www.apdaparkinson.org>.
International Tremor Foundation. 7046 West 105th St.,
Overland Park, KS 66212. (913) 341-3880.
National Parkinson Foundation. 1501 N.W. 9th Ave.,
Miami, FL 33136-1494. (800) 327-4545. <http://
www.parkinson.org>.

Trichinosis

Tretinoin see Antiacne drugs
Trichinella spiralis infectio see Trichinosis
Trichiniasis see Trichinosis

Trichinosis
Definition
Trichinosis is a disease caused by a roundworm
(nematode) called Trichinella spiralis. An individual
worm of this species is called a trichina, from the
Greek word meaning ‘‘hairlike.’’ Trichinae can be
readily avoided by proper handling and cooking of
certain meats, particularly pork products.

Description
The life cycle of T. spiralis includes several different stages. The adult trichina lives in the intestinal
lining of such meat-eating animals as swine, bears,
walrus, and rodents. After mating, the male worm
dies while the female goes on to produce the
offspring.
Roundworms have a stage of development called
the embryonic stage, which in many species occurs
after birth. In trichinae, however, this embryonic
stage occurs within the uterus of the female, so the
offspring that are ultimately discharged into the host’s
intestinal lining are in the larval second stage of life.
These larvae–about 1500 from each female worm–
travel through the circulatory system to the heart,
then through the blood vessels leading to striated
muscle (the muscle of the skeletal system and the
heart). Most larvae that cannot find suitable locations
in striated muscle will die.
Those larvae that reach striated muscle will grow
to a length of about one millimeter, coil themselves,
and enclose themselves within a protective wall called
a cyst. This process is referred to as encysting. The
worms in the cysts can live for up to ten years in this
form.
A pig that has been infected with T. spiralis, then,
has thousands of cysts lying dormant within its muscles– the very muscles that humans look forward to
consuming in the form of pork chops, ham, barbecued
ribs, etc. When humans sit down to a delicious meal of
undercooked, trichina-infected pig dinner, they are
ingesting T. spiralis cysts. The cyst walls are broken
down by the usual process of food digestion in the
stomach, allowing the larvae to escape into the new
3782

host’s intestines. There the larvae mature to become
adult worms, capable of producing a new crop of
larvae. When these new larvae hatch, they begin their
migration throughout the human host’s bloodstream
to his or her muscles, where they live for a short while
before encysting.

Causes and symptoms
Human hosts who eat meat infested with trichinae may experience symptoms in varying degrees. If
the meat ingested has only a few cysts, then the
human host’s load of parasites (worm burden) is
said to be relatively small, and symptoms will be
moderate. In fact, many trichinosis infections are
subclinical, which means that the symptoms are so
mild that the infection remains undiagnosed. In a
host with a greater worm burden, the initial symptoms will be caused by the presence of the adult
worms in the intestine. These symptoms usually
include fever, diarrhea, abdominal pain, and perhaps
vomiting. The symptoms begin about one to two days
after eating the contaminated meat, and may last for
a week or so.
When the larvae begin their migration through the
blood vessels, the host will begin to experience symptoms that affect the whole body (systemic symptoms),
such as fever; swelling of the face and the area around
the eyes; rash; bleeding into the nail beds, retina, and
whites of the eyes; and cough. In very severe cases of
trichinosis, inflammation of the heart muscle (myocarditis), lungs (pneumonitis), or brain (encephalitis) may
occur. These symptoms can lead to the few deaths
caused by trichinosis.
The larvae begin to burrow into the host’s muscles
and form cysts within two to three weeks of the initial
infection. This encysting produces signs of muscle
inflammation (myositis) including swelling of the
affected muscle groups, pain, and weakness. The
most frequently affected muscles are the muscles outside the eye (extraocular muscles) that control eye
movements; the muscles of the jaw, neck, and upper
arm (biceps muscle); the muscles of the lower back
(lumbar region); and the diaphragm, which is the
muscle that separates the abdominal and chest cavities
and aids in breathing.
The symptoms of trichinosis are at their most
severe at about three weeks after infection, and
decrease very slowly in their severity. Recovery is
extremely gradual, and symptoms may last for as
long as three months. Fatigue and muscle pain (myalgia) may take several more months to subside.
GALE ENCYCLOPEDIA OF MEDICINE

Trichinosis
A Trichinella spiralis cyst in striated muscle tissue. T. spiralis cysts can survive up to ten years in this form. (JLM Visuals.
Reproduced by permission.)

Diagnosis
An initial diagnosis of trichinosis relies heavily on
the presence of its classic symptoms–swelling around
the eyes, muscle inflammation, fever, and high levels
of a certain type of white blood cell (eosinophils)–
coupled with the patient’s history. If the patient
reports having eaten undercooked meat from an animal known to be a potential carrier of trichinosis, the
doctor may order a muscle biopsy to confirm the
diagnosis. By the third or fourth week of infection,
muscle biopsies usually indicate the presence of larvae.
Stool tests rarely reveal adult worms, although larvae
can sometimes be found in blood or duodenal washings after the second week of infection. The blood test
that is the most specific for trichinosis is the bentonite
flocculation (BF) test.
T. spiralis can infect a number of different animal
species used for food. The most common food culprit
in the United States has been pork sausage, while
outbreaks in Europe have caused by wild boar and
horse meat. Outbreaks of trichinosis in Asia and
GALE ENCYCLOPEDIA OF MEDICINE

Africa have been traced to dog meat, and outbreaks
in Northern Canada have resulted from consumption
of walrus and bear meat.

Treatment
Supportive care
Treatment of trichinosis is primarily aimed at
decreasing the severity of the symptoms. Symptomatic
relief includes bed rest and medications to relieve fever
and muscle pain. The medications most commonly
given are aspirin and nonsteroidal anti-inflammatory
drugs (NSAIDs). Steroids such as prednisone
(Deltasone, Meticorten) are reserved for the most
severe cases of muscle inflammation, or for complicated
cases that include myocarditis.
Anthelminthic medications
In addition to medications for pain relief, trichinosis can be treated with drugs that are called antiworm medications or anthelminthics. Two related
3783

Trichomoniasis

KEY TERMS
Anthelminthic—A type of medication that is given
to destroy or eliminate parasitic worms.
Cyst—In the life cycle of the round worm, a protective, walled-off capsule in which the larvae lie
dormant.
Embryonic—In the life cycle of the round worm, a
very early life stage occurring within the uterus of
the female round worm.
Host—The animal within which a parasite lives,
and from which the parasite receives its nutrition.
Inflammation—A reaction within the body to an
invader (virus, bacteria, fungus, worm, etc.) or to
tissue injury. The classic signs of inflammation
include redness, heat, pain, and loss of function.
Larva—In the life cycle of the round worm, the
second stage of life, sometimes considered the
‘‘adolescent’’ stage.
Nematode—A type of roundworm with a long,
unsegmented body, usually parasitic on animals
or plants.
Striated muscle—Also known as striped muscle; it
includes muscles of the skeletal system and of the
heart.
Trichina—An individual example of Trichinella
spiralis.

anti-worm medications, mebendazole (Vermox) and
thiabendazole (Mintezol), have been reported to be
effective against intestinal larvae, but not against larvae encysted in the muscles. In particular, thiabendazole has worked best when given to patients who knew
within 24 hours that they had eaten infested meat.
Thiabendazole has, however, anti-inflammatory
properties that can relieve some of the pain during
the muscle stage of trichinosis.

Prognosis
The prognosis for recovery from trichinosis is
generally good. Most people with the disease are
unaware that they have even been infected. It is estimated that between 150,000 and 300,00 people in
the United States become infected yearly, so that at
any given time, 1.5 million people have T. spiralis
infections. Most of these people have such light
cases that trichinosis is never identified. Worm burden is measured in larvae per gram of muscle tissue;
3784

people with 10 or fewer larvae per gram of muscle
tissue usually have no significant symptoms. When
the number climbs to 100 larvae per gram of muscle
tissue, the symptoms become noticeable. People with
over 1000 larvae per gram of muscle tissue are usually
extremely ill, and often die. The mortality rate of
trichinosis is about 1%.

Prevention
Prevention of trichinosis is relatively simple.
Swine should be fed only grain or cooked garbage
because uncooked garbage may contain contaminated pork scraps. Meat from animals prone to trichinosis infection should be cooked or smoked
thoroughly until it is no longer pink. Freezing meat
at an adequately low temperature (58F/–158C for
three weeks) can kill most encysted larvae, except
for species which infect such arctic mammals as walrus or bear.
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Trichomonas vaginalis infection see
Trichomoniasis

Trichomoniasis
Definition
Trichomoniasis refers to an infection of the genital and urinary tract. It is the most common sexually
transmitted disease, affecting about 120 million
women worldwide each year.

Description
Trichomoniasis is caused by a protozoan (the
smallest, single-celled members of the animal kingdom). Trichomonas vaginalis is passed almost 100%
of the time through sexual contact. Trichomoniasis is
primarily an infection of women’s vaginal and urinary
tracts. A woman is most susceptible to infection just
after having completed her menstrual period. Men
may carry the organism unknowingly, since infection
in men may cause mild or no symptoms.
GALE ENCYCLOPEDIA OF MEDICINE

Metronidazole—An anti-infective agent regarded
as the best available drug for treating trichomoniasis. It is sold under the trade names Flagyl and
MetroGel.
Protozoan—A one-celled organism belonging to
the simplest phylum of the animal kingdom.
Trichomoniasis is caused by a protozoan.
Urethritis—Inflammation of the urethra, which is
the canal that carries urine from the bladder to the
outside of the body.
A close up image of Trichomonas vaginalis, the parasite that
causes vaginitis in humans. (Custom Medical Stock Photo.
Reproduced by permission.)

Causes and symptoms
Because trichomoniasis is a sexually transmitted
disease, it occurs more often in individuals who have
multiple sexual partners. The protozoan is passed to an
individual by contact within the body fluids of an infected
sexual partner. It often occurs simultaneously with other
sexually transmitted diseases, especially gonorrhea.

Trichomoniasis tends to be underdiagnosed in
men because of the relative mildness of symptoms in
men and insufficiently sensitive diagnostic tests. The
recent introduction of DNA amplification, however,
indicates that the incidence of trichomoniasis in men is
much higher than was previously thought.

Treatment

In women, the symptoms of trichomoniasis
include an unpleasant vaginal odor, and a heavy,
frothy, yellow discharge from the vagina. The genital
area (vulva) is often very itchy, and there is frequently
pain with urination or with sexual intercourse. The
labia (lips) of the vagina, the vagina itself, and the
cervix (the narrowed, lowest segment of the uterus
which extends into the upper part of the vagina) will
be bright red and irritated.

The usual treatment is a single large dose of
metronidazole, or split doses over the course of a
week. Sexual partners of an infected individual must
all be treated, to prevent the infection being passed
back and forth.

In men, there are usually no symptoms at all.
Occasionally, a man will notice a small amount of
yellowish discharge from his penis, usually first thing
in the morning. There may be some inflammation of
the urethra, or urethritis, which produces mild discomfort while urinating.

As of late 2003, the number of cases of metronidazole-resistant trichomoniasis appears to be increasing rapidly. Some success has been reported with
the broad-spectrum anti-parasitic drug nitazoxanide,
but further research needs to be done. A group of
researchers in Thailand is currently investigating
the effectiveness of a group of drugs known as bisquaternary quinolinium salt compounds in treating
trichomoniasis.

The use of antibiotics is a contributing factor to
recurrent trichomoniasis in some women because antibiotics affect the balance of bacteria in the vagina,
allowing such organisms as T. vaginalis to multiply
more rapidly.

Diagnosis
Diagnosis is easily made by taking a sample of the
discharge from the women’s vagina, or from the opening of the man’s penis. The sample is put on a slide,
and viewed under a microscope. The protozoa, which
are able to move about, are easily viewed.
GALE ENCYCLOPEDIA OF MEDICINE

Women who are taking antibiotics for other illnesses should speak to their health care provider about
the possibile effects of the medication(s) on the balance of organisms in their vagina.

Alternative treatment
Cure of trichomoniasis may be difficult to achieve
with alternative treatments. Some practitioners suggest
eliminating sweets and carbohydrates from the diet
and supplementing with antioxidants, including vitamins A, C, and E, and zinc. Naturopaths may recommend treatment with two douches (a wash used inside
the vagina), alternating one in the morning and one at
3785

Trichomoniasis

KEY TERMS

Tricuspid valve insufficiency

bedtime. One douche contains the herbs calendula
(Calendula officinalis), goldenseal (Hydrastis canadensis), and echinacea (Echinacea spp.); the other douche
contains plain yogurt. The herbal douche helps to kill
the protozoa, while the yogurt reestablishes healthy
flora in the vagina. Another herbal remedy that is
sometimes used is tea tree oil. Acidifying the vagina
by douching with boric acid or vinegar may also be
useful.

Prognosis
Prognosis is excellent with appropriate treatment
of the patient and all sexual partners. Without treatment, the infection can smolder on for a very long
time, and can be passed to all sexual partners.

Prevention
All sexually transmitted diseases can be prevented
by using adequate protection during sexual intercourse. Effective forms of protection include male
and female condoms.
Resources
BOOKS

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Vaginitis.’’ New York: Simon & Schuster, 2002.

ncidod/dpd/parasites/trichomonas/
factsht_trichomonas.htm>.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

Trichotillomania see Alopecia
Trichuriasis see Roundworm infections
Tricuspid incompetence see Tricuspid valve
insufficiency
Tricuspid regurgitation see Tricuspid valve
insufficiency
Tricuspid stenosis see Tricuspid valve
stenosis

Tricuspid valve insufficiency
Definition
Tricuspid valve insufficiency occurs when a tricuspid valve does not close tightly enough to prevent
leakage. This condition is also called tricuspid valve
regurgitation and tricuspid incompetence.

PERIODICALS

Chavalitshewinkoon-Petmitr, P., M. Ramdja,S.
Kajorndechakiat, et al. ‘‘In vitro Susceptibility of
Trichomonas vaginalis to AT-Specific Minor Groove
Binding Drugs’’ Journal of Antimicrobial Chemotherapy
52 (August 2003): 287–289.
Ching, Susanne, and Phuong H. Nguyen. ‘‘Vaginitis.’’
eMedicine April 5, 2002. <http://emedicine.com/med/
topic2358.htm>.
Dunne, R. L., L. A. Dunn, P. Upcroft, et al. ‘‘Drug
Resistance in the Sexually Transmitted Protozoan
Trichomonas vaginalis.’’ Cell Research 13 (August
2003): 239–249.
Pirotta, M. V., J. M. Gunn, and P. Chondros. ‘‘‘Not Thrush
Again!’ Women’s Experience of Post-Antibiotic
Vulvovaginitis.’’ Medical Journal of Australia 179 (July
7, 2003): 47–49.
Schwebke, J. R., and E. W. Hook, 3rd. ‘‘High Rates of
Trichomonas vaginalis Among Men Attending a
Sexually Transmitted Diseases Clinic: Implications for
Screening and Urethritis Management.’’ Journal of
Infectious Diseases 188 (August 1, 2003): 465–468.
OTHER

Centers for Disease Control and Prevention (CDC). ‘‘Fact
Sheet:Trichomonas Infection.’’ <http://www.cdc.gov/
3786

Description
The tricuspid valve is located between the right
atrium and the right ventricle of the heart. When the
right ventricle contracts, it is supposed to pump blood
forward into the lungs. If the tricuspid valve does not
close tightly, some of that blood leaks back into the
right atrium. When the atrium receives its usual quantity of blood from veins leading to the heart, plus the
leaking blood, the pressure inside the atrium increases.
This higher pressure creates resistance to the flow of
blood in the veins that enter the atrium from the body.
In addition, this increase in pressure causes the right
atrium to enlarge over time. Congestion from fluid
buildup occurs, particularly in the liver and legs.

Causes and symptoms
If a person has serious lung disease or a narrowing
of the pulmonary valve, the right ventricle must pump
harder to force the blood through the pulmonary
valve. In order to pump harder, the right ventricle
enlarges and the valve opening stretches, causing the
valve to leak.
GALE ENCYCLOPEDIA OF MEDICINE

Atrial fibrillation—A rapid, uncoordinated quivering of the upper chamber of the heart.
Atrium—The upper chamber of the heart.
Pulmonary valve—The valve at the opening from
the right ventricle to the artery that leads to the
lungs.

This echocardiogram of the heart shows tricuspid valve
insufficiency. (Custom Medical Stock Photo. Reproduced by
permission.)

Tricuspid valve insufficiency usually produces
such vague symptoms, as general weakness and fatigue. As the conditions worsens, a person experiences
pain in the upper right part of the abdomen, caused by
a congested and enlarged liver. The legs may also swell
(edema).
An enlarged right atrium can cause atrial fibrillation (the atria flutters, rather than pumping in a regular rhythm) and severe tricuspid regurgitation of
blood, which can eventually lead to congestive heart
failure.

Diagnosis
A leaky valve can be heard with a stethoscope; the
sound is called a heart murmur. Additional support
for diagnosing tricuspid valve insufficiency comes
from a medical history, physical exam, and chest
x ray. Further testing with echocardiography, to show
an image of the leakage and its severity, is the most
helpful diagnostic test for this condition.

Treatment
Tricuspid valve insufficiency itself usually does
not require treatment, since a tiny leakage occurs in
most normal people. In certain cases, however, if there
is underlying pulmonary valve disease or lung disease,
those conditions should be treated.
If irregular heart rhythms or heart failure are present, they are usually treated independently of the
valve insufficiency.
Since a person with known tricuspid valve insufficiency is at risk for infections of the heart, antibiotics
GALE ENCYCLOPEDIA OF MEDICINE

should be taken before and after oral or dental surgery, or urologic procedures.

Prognosis
Tricuspid valve insufficiency is not usually considered to be serious. If it is the result of other cardiopulmonary disease, the extent of those conditions
effect the prognosis.

Prevention
In general, tricuspid valve insufficiency cannot be
prevented.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave., Dallas,
TX 75231-4596. (214) 373-6300 or (800) 242-8721.
inquire@heart.org. <http://
www.americanheart.org>.

Dorothy Elinor Stonely

Tricuspid valve stenosis
Definition
Tricuspid valve stenosis is a narrowing or stiffening of the opening in the valve. This stenosis causes
increased resistance to blood flow through the valve.

Description
The tricuspid valve is located between the right
atrium and the right ventricle of the heart. It is the
largest of the four valves in the heart. When the tricuspid valve is narrowed or stiffened, it decreases the
amount of blood that can flow through it. This
3787

Tricuspid valve stenosis

KEY TERMS

Trigeminal neuralgia

Prevention

KEY TERMS
Rheumatic fever—An inflammatory illness that can
follow strep throat, and could cause heart damage.

decrease raises the pressure in the right atrium and
causes the atrium to enlarge. It also causes the right
ventricle to shrink, and lowers the cardiac output.

Causes and symptoms
Tricuspid valve stenosis is most often the result of
rheumatic fever. On rare occasions, it is caused by a
tumor or disease of the connective tissue. The rarest
cause is a birth defect.
A person with tricuspid valve stenosis may experience generalized weakness and fatigue. Many people
have palpitations and can feel fluttering in their neck.
Over time, there may be pain in the upper right abdomen, due to increased congestion and enlargement of
the liver.

Rheumatic fever, the usual cause of tricuspid
valve stenosis, has almost disappeared in North
America and western Europe. Therefore, the number
of people who acquired this condition in childhood
will decline over time.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300 or (800) 242-8721. inquire
@heart.org. <http://www.americanheart.org>.

Dorothy Elinor Stonely

Tricyclic antidepressants see
Antidepressants, tricyclic

Trigeminal neuralgia
Definition

Diagnosis
The noise produced by blood trying to flow
through a stenotic valve can be heard with a stethoscope, and is referred to as a murmur. An x ray of the
chest will show the right atrium to be enlarged.
Further support for this diagnosis is found on an
echocardiogram of the heart, which will show an
image of the stenotic valve and measure its severity.

Treatment
Tricuspid valve stenosis itself usually doesn’t
require treatment. However, if there is damage to
other valves in the heart as well, then surgical repair
or replacement must be considered.
Since a person with known tricuspid valve stenosis
is at risk for infections of the heart, antibiotics should
be taken before and after oral or dental surgery, or
urologic procedures.

Prognosis
Mild tricuspid valve stenosis is not usually considered cause for surgery. The decision to repair or
replace the tricuspid valve is often based on the health
of the aortic and mitral valves, rather than on the
severity of stenosis in the tricuspid valve.
3788

Trigeminal neuralgia is a disorder of the trigeminal nerve (the fifth cranial nerve) that causes episodes
of sharp, stabbing pain in the cheek, lips, gums, or chin
on one side of the face.

Description
The trigeminal nerve, which is divided into three
branches, is responsible for chewing, for producing
saliva and tears, and for sending facial sensations to
the brain. When this nerve breaks down for some
reason, it can trigger brief but agonizing sizzles of
pain on one side of the face.
This condition is unusual in those under age 50
and more often occurs after 70. Women are three times
more likely to have the condition than are men. When
trigeminal neuralgia does occur in younger people, it is
often associated with multiple sclerosis.
The pain, while brief, is so severe that the sufferer
often can’t do anything else while the attack lasts.
People with this pain often wince or twitch, which is
where trigeminal neuralgia gets its French nickname
tic douloureux, meaning ‘‘painful twitch.’’

Causes and symptoms
The origin of trigeminal neuralgia is not certain,
but scientists believe it may be caused by degeneration,
GALE ENCYCLOPEDIA OF MEDICINE

Trigeminal neuralgia

Ophthalmic branch

Maxillary branch

Mandibular branch

Trigeminal neuralgia is a disorder of the trigeminal nerve (which is divided into three branches, as illustrated above) that causes
episodes of sharp, stabbing pain in the cheek, lips, gums, or chin on one side of the face. The origin of this disorder is not certain,
but scientists believe it may be caused by degeneration, pressure, or irritation of the trigeminal nerve. (Illustration by Electronic
Illustrators Group.)

pressure, or irritation of the trigeminal nerve. Some
doctors believe the pain may be triggered by pressure
from a nearby abnormally-formed artery lying too
close to the nerve.
Any part of the three branches of the trigeminal
nerve may be affected. Neuralgia of the first branch
leads to pain around the eyes and over the forehead;
the second branch causes pain in the upper lip, nose
and cheek; the third branch causes pain on the side of
the tongue and lower lip.
The first episodes are usually fairly mild and brief,
and it may be minutes, hours, or weeks before the next
attack. However, attacks tend to occur in clumps that
may last for weeks at a time. As the sufferer ages, the
episodes become more frequent and painful, until the
person begins to live in constant fear of the next one.
The momentary bursts of pain usually begin from
the same spot on the face each time. The pain can be
triggered by touching the area, washing, shaving, eating, drinking, or even talking. Even a cool breeze
across the face can set off an attack. Pain is more
severe at the ends of the affected nerve, especially
over the lip, chin, nostrils, or teeth.
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Diagnosis is usually made by eliminating other
problems that could cause similar pain in teeth, jaw,
head, or sinuses. Because patients with the condition
tend to avoid trigger points, avoiding chewing, shaving, touching or washing their faces can be a clue to
diagnosis of trigeminal neuralgia.

Treatment
It is not easy to treat trigeminal neuralgia. Pain
can be suppressed by a range of medicines, including
the anti-epilepsy medicines carbamazepine (Tegretol)
or phenytoin (Dilantin). These drugs slow down the
nerve signals at certain nerve terminals, which eases
the pain. However, these drugs cause a wide range of
side effects, including nausea, dizziness, drowsiness,
liver problems, and skin allergies. Some people
develop resistance to the drugs or they can’t tolerate
the high dosage needed to control the discomfort. If
the medicines are stopped, the pain usually returns.
If drug treatment fails, surgical treatment to block
pain signals from the nerve may be effective. Radio3789

Trigger finger

KEY TERMS
Multiple sclerosis—A progressive disease of the
central nervous system in which the coverings of
nerves in the brain and spinal cord are destroyed.

frequency waves, gamma rays, or glycerol injections
can deaden the nerve (and hence the pain). An operation that frees the nerve from whatever is compressing
it (blood vessel or tumor) can permanently relieve
pain, but this major neurosurgical procedure carries
its own risks and complications. Alternatively, a new
procedure seeks to place a cushioning sponge between
the nerve and a pulsating artery wrapping around it to
soothe the irritated nerve.

Prognosis
Although the pain is momentarily incapacitating,
it’s not life-threatening. As the person ages, the attacks
can be expected to occur more and more frequently.

Trigger finger
Definition
Trigger finger is the popular name of stenosing
tenosynovitis, a painful condition in which a finger or
thumb locks when it is bent (flexed) or straightened
(extended).

Description
Tendons are tough, fibrous cords that connect
muscles to bones. Tendons must slide easily through
their protective coverings (tendon sheaths). The finger
and thumb bones have tendons that are responsible
for bending and straightening the fingers. Problems
start when a tendon sheath narrows (stenosis) and the
outer covering of the tendon becomes inflamed (tenosynovitis). The tendon swells because of the constriction, sometimes forming a nodule, and is no longer
able to move smoothly through its sheath. As a result,
a finger may lock in an upward position as the person
tries to straighten it. The condition usually happens in
the ring and middle fingers and is more common in
women, typically over age 30. In infants and small
children, the condition generally occurs in the thumb.

Prevention
While the condition itself can’t be prevented, there
are a number of things patients can do to avoid triggering attacks:


wash with cotton pads and warm water over the face



rinse the mouth with water after eating, if toothbrushing triggers pain



eat and drink food and beverages at room
temperature



chew on the unaffected side



eat soft foods, if eating is becoming a problem

Causes and symptoms
Trigger finger is often an overuse injury because of
repetitive or frequent movement of the fingers. Trigger
finger may happen because a person performs the same
manipulation over and over on a job, from squeezing
and gripping during a weekend of heavy pruning and
gardening, or from such hobbies as playing a musical
instrument or crocheting. Trigger finger may also result
from trauma or accident. The symptoms of trigger
finger are pain in the fingers and ‘‘popping’’ sensations.
Sometimes the finger may lock down into the palm or
lock out straight. Symptoms are usually worse in the
morning and improve during the day.

Resources

Diagnosis

ORGANIZATIONS

Chronic Pain Outreach. 822 Wycliff Ct., Manassas, VA
22110. (703) 368-7357.
National Chronic Pain Outreach Association, Inc. P.O. Box
274, Millboro, VA 24460- 9606. (540) 997-5004.
National Institute of Neurological Disorders and Stroke.
P.O. Box 5801, Bethesda, MD 20824. (800) 352-9424.
<http://www.ninds.nih.gov/index.htm>.
Trigeminal Neuralgia Association. P.O. Box 785, Barnegat
Light, NJ 08006. (609) 361-1014.

Carol A. Turkington
3790

The diagnosis of trigger finger and thumb is
obvious on physical examination. Often there is a
click that can be felt as the nodule passes through the
sheath. Most cases are uncomplicated although X rays
are often taken to rule out other injuries or disease
such as arthritis.

Treatment
Initial treatment for mild or infrequent symptoms of
trigger finger include rest, avoiding or modifying those
GALE ENCYCLOPEDIA OF MEDICINE

Microcirculation—The passage of blood in the
smallest blood vessels of the body, such as the
capillaries in the hand and fingers.
Myofascial—The fibrous tissue that encloses and
separates layers of muscles.
Nodule—A swelling or knob that may form on a
tendon and make it difficult to slide smoothly
through its sheath.
Stenosis—Narrowing of a passageway or opening
in the body. In trigger finger it is the tendon sheath
that narrows.
Synovial tendon sheath—Where the tendons cross
joints, they are sheathed in thin membranes known
as synovium, which provide lubrication to
decrease friction.
Tendon sheath—A membrane covering a tendon.
Tenosynovitis—Inflammation of a tendon and its
enveloping sheath, usually resulting from overuse
injury.

activities that caused the inflammation, and the use of a
nonsteroidal anti-inflammatory drug (NSAID) such as
ibuprofen. This may relieve the swelling and inflammation that resulted in the constriction of the sheath and the
restriction of the tendon. Injection of a steroid medication (cortisone) into the tendon sheath is the next option
to treat trigger finger. Depending on the severity, there
may be one more injection a week later. Two-thirds of
patients improve after one injection. Some physicians
will splint the finger in extension after the injection.
In severe cases that do not respond to injections and
the finger or thumb remains in a locked position, surgery
may be required to relieve the symptoms. A local anesthetic is used for the surgical procedure performed on an
outpatient basis. An incision is made by a surgeon in the
palm of the hand at the base of the affected finger or thumb
to relieve the constriction of the tendon. Recovery may
take up to four weeks. Sometimes physical therapy of
the hand is required after surgery to regain good use.

Alternative treatment
Treatment should begin when a person starts having difficulty moving the fingers. If started early, noninvasive measures have a good chance for success.
Alternative treatments include acupuncture to facilitate healing and microcirculation, pulsed ultrasound,
and myofascial release work for the affected area.
GALE ENCYCLOPEDIA OF MEDICINE

At least half of cases can be cured non-surgically.
The key to successful treatment is early intervention. A
mistake people make is trying to work through the
pain. Diabetics have a higher incidence of the condition and are sometimes left with a disability.

Prevention
Taking frequent breaks from a repetitive activity
will do much to prevent the condition. Depending on
the intensity, that may mean a 10-minute break every
hour from the repetitive activity. The break should be
spent stretching the hands and arms and generally
moving around.
Resources
PERIODICALS

‘‘Ask the Mayo Physician.’’ HealthOasis MayoClinic May 4,
2000.
Phillips, D. F. ‘‘New Paradigms Sought to Explain
Occupational andEnvironmental Disease.’’ JAMA
January 6, 1999.
Stroud, R. ‘‘Minimally Invasive Surgical Techniques of the
Hand andUpper Extremities.’’ Orthopedic Technology
Review September2000: 18.
ORGANIZATIONS

American Society for Surgery of the Hand. 6300 N. River
Rd., Suite 600, Rosemont, IL 60018. <http://
www.hand-surg.org>.
OTHER

Jameson DC, CCSP, Timothy J.
‘‘Explanation,Treatment,and Prevention of Trigger
Finger.’’GuitarBase Articles. <http://www.gbase.com/
articles/med/med4.html>.

Ruthan Brodsky

Triglycerides test
Definition
Triglycerides test is a blood test to determine the
amount of triglycerides, a form of fat, in the blood.

Purpose
The triglycerides test is one of the screening tests
for excess lipids (fats) in the blood. It is usually part of
an evaluation of risk factors for heart disease.
3791

Triglycerides test

Prognosis

KEY TERMS

Triple screen

Description
Triglycerides are a form of fat that comes from
foods. They can also be made and stored in the
body and are used as an energy source. High levels
of triglycerides in the blood can mean that there
is too much fat in the diet. Hypertriglyceridemia
(high levels of triglycerides) is associated with
coronary heart disease, especially since elevated
triglycerides levels are often associated with
unhealthy low levels of hyper-density lipoproteins
(the ‘‘good’’ cholesterol), which are necessary for
good health.

Preparation
For triglycerides testing, blood is drawn from a
vein in the arm. A vein at the inside of the elbow
or on the back of the hand is usually selected. The
area where the needle will be inserted is cleaned
with antiseptic. A small needle is inserted through
the skin and into the vein, allowing a small amount
of blood to flow into a collection tube or syringe.
Once the blood is collected, the needle is removed
from the puncture site.
Before the blood test, the patient may be required
to refrain from eating food from eight to–12 hours.
Patients should not drink alcohol for 24 hours before
the test. Some drugs may affect the test and the patient
may be asked to cease taking certain medications
before the test. Oral contraceptives, estrogen, and
cholestyramine (a drug used to treat high cholesterol)
can increase triglyceride levels. Ascorbic acid (vitamin
C), asparaginase (an enzyme), and various drugs used
to treat high blood lipids, can decrease blood triglyceride levels. These substances should not be taken
prior to this test.

Normal results
The normal range of triglycerides in the blood
depends on the age and gender of the patient.
Women naturally have higher levels of triglycerides
than men. Pregnancy can also increase triglyceride
levels. As people age and gain weight, triglyceride levels generally increase. For adults, a normal
level is considered to be less than 200 mg/dl (milligrams per deciliter). Levels from 200–400 mg/dL are
considered borderline high.

Abnormal results
Triglyceride levels ranging from 400-1000 mg/dL
are considered high and levels greater than 1000 mg/
dL are considered very high. High levels of triglycerides may indicate liver disease (cirrhosis), an underactive thyroid problem, uncontrolled diabetes, an
infection of the pancreas (pancreatitis), kidney disease,
or a diet too low in protein and too high in
carbohydrates.
Extremely low triglycerides levels (less than 10
mg/dL) can also indicate a problem. Low levels may
indicate malnutrition (not enough nutrients in the
diet), malabsorption (inadequate absorption of nutrients in the intestinal tract), a diet too low in fat, or an
overactive thyroid problem.
Resources
OTHER

‘‘Triglyceride levels.’’ HealthAnswers.com <http://
www.healthanswers.co>.
‘‘Triglycerides.’’ ThriveOnline. <http://
thriveonline.oxygen.com>.

Altha Roberts Edgren

Aftercare
After the blood sample has been taken and the
needle withdrawn from the puncture site, a cotton ball
or gauze pad may be placed over the site and direct
pressure applied to reduce bleeding. A piece of surgical
tape or gauze adhesive bandage strip may be secured
over the site to prevent further bleeding.

Risks
There is a very small risk that the puncture site
may bleed excessively, a bruise or infection may
develop at the site, or it may take several punctures
to locate a vein. Some patients may feel faint or lightheaded when blood is drawn.
3792

Triiodothyronine test see Thyroid function
tests

Triple screen
Definition
Triple screen is a blood test offered to pregnant
women during the 16th-18th week of pregnancy to
help identify if the unborn baby is at risk for birth
defects.
GALE ENCYCLOPEDIA OF MEDICINE

Researchers have found that women carrying a
fetus with Down syndrome tend to have three substances in their blood in a distinctive abnormal pattern. Both alpha-fetoprotein (AFP), a protein
produced by the fetus, and unconjugated estriol
(uE3), a hormone manufactured by both the fetus
and the placenta, are lower than normal, while
human chorionic gonadotropin (hCG), a hormone
produced in the placenta, is higher. The level of each
substance is then divided by the median concentration
of that substance for the given week of pregnancy to
generate a multiple of the median value (MOM).
These values, along with other characteristics of the
mother, such as her age, are analyzed by a computer
program to indicate the probability that the fetus has
Down syndrome. Down syndrome is a condition that
includes mental retardation, skeletal abnormalities
such as upslanted eyes and cleft palate, and organ
abnormalities such as heart disease and intestinal
obstruction.
Guidelines developed from this research help
healthcare workers to determine whether the risk for
any one pregnancy is clearly different from that for the
general population of the same age. For example, the
average 25-year-old woman has one chance in a 1,000
of bearing a Down syndrome baby. After her blood is
analyzed for the three hormones, her risk can be refigured. It might be considerably lower—or higher—
than average.
The triple screen was first aimed toward detecting
fetuses at high risk for Down syndrome, an abnormality that comes about when, at fertilization, the
embryo receives three copies of chromosome 21
instead of the usual two. For unknown reasons, extra
amounts of genetic material are usually associated
with severe developmental defects. Although Down
syndrome is the most common such disorder, it is by
no means the only one. Chromosomes 13 or 18 can
also turn up as a triple set (or trisomy). An abnormal
pattern of the three hormones sometimes signals one
of these trisomies or another, more rare chromosomal
disorder.

fetus lowers the false-positive and false-negative rates
associated with this screening test.

Description
Prior to 1964, when the association between low
levels of AFP and an increased risk for Down syndrome was reported, risk assessment for chromosomal
diseases was based upon maternal age. At age 35, the
risk of carrying a Down syndrome pregnancy is
approximately one in 270, and this was deemed sufficient to warrant amniocentesis, a more accurate but
invasive test that involves using a needle to draw out a
sample of the embryonic fluid that surrounds the
fetus. However, three of four Down syndrome pregnancies occur in women under 35 years old. When
AFP testing was used along with maternal age, the
rate of detection of Down syndrome increased to
about 45%, but this level of sensitivity did not justify
the screening of younger women because of the risk of
miscarriage. The inclusion of uE3 and hCG testing has
improved the detection rate to approximately 65-80%
of cases for all age groups. The triple screen test costs
$90-250 and is covered by most insurance plans.

Preparation
There is no specific physical preparation for this
test. Fasting is not required.

Aftercare
After the blood sample is drawn, pressure should
be applied to the puncture site until the bleeding stops
to reduce bruising. A bandage or taped ball of cotton
may be applied to the site. A warm pack may be
applied to the site to relieve discomfort.

Risks
The complications associated with drawing blood
are minimal, but may include bleeding from the puncture site, feeling faint or lightheaded after the blood is
drawn, or blood accumulating under the puncture site
(hematoma).

Precautions
It is important that the correct age of the unborn
baby be determined by last menstrual period dating
and recorded for the risk calculation. Errors in determining the age of the fetus lead to errors when interpreting the test results. Since an AFP test is only a
screening tool, an abnormal test result is not necessarily indicative of a birth defect. Accurate dating of the
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Results are expressed as multiples of the median
value used by the laboratory. Normal ranges
expressed in concentration (for example, ng/mL) are
dependent upon the age of the fetus, but MOMs are
age-adjusted and do not change. These values are used
to calculate risk. If the multiple of the median value is
3793

Triple screen

Purpose

Tropical spastic paraparesis

KEY TERMS

Pouliot, Janine S. ‘‘Triple Screen.’’Better Homes and
Gardens(October 2003): 256.
ORGANIZATION

Amniocentesis—A test performed to determine the
health, sex, or genetic constitution of a fetus by
taking a sample of amniotic fluid through a needle
inserted into the womb of the mother.
Amniotic fluid—The fluid that surrounds a fetus
while it is developing. It is the fluid that flows out
in the ‘‘breaking of the water’’ before a baby is
born.
Down syndrome—A genetic disorder characterized by a broad skull, blunt facial features, short
stature, and learning difficulties. It is caused by the
presence of an extra copy of chromosome 21.
Placenta—An organ that develops inside the uterus
of pregnant women to supply food and oxygen to
the fetus through the umbilical cord.

National Down Syndrome Society. 666 Broadway, New
York, NY 10012. (212) 460-9330 or (800) 221-4602.
info@ndss.org. http://www.ndss.org.

Ken R. Wells

Triplets see Multiple pregnancy
Trisomy 18 see Edwards’ syndrome
Trisomy G syndrome see Down syndrome
Trisomy 13 see Patau’s syndrome
Trobofloxacin see Fluoroquinolones

Tropical spastic paraparesis
below 2.0 MOM or 2.5 MOM (depending on the
laboratory), the fetus is considered to be at a lower
risk for a genetic defect.

Abnormal results
If the multiple of the median value is above 2.0
MOM or 2.5 MOM (depending on the laboratory), the
fetus is considered to be at a higher risk for a genetic
defect. The MOM value for amniotic fluid is then used
to calculate the exact probability the fetus is affected
(1:100, for example). With respect to Down syndrome
and trisomy 18, the MOM values are also used in the
calculation of probability. The woman is considered to
be ‘‘high risk’’ or ‘‘screen positive’’ for Down syndrome
if the risk is greater than the standard risk for women
who are 35 years old or older (one in 270). For trisomy
18, the cut-off is one in 150. In one study the triple
marker screen test had a detection rate for Down syndrome of 67% and a false positive rate of 5%.
Resources
BOOKS

Health Education Board for Scotland.A Parent’s Guide to
the Screening Test for Spina Bifida and Down Syndrome:
A Blood Test You Can Chose to Have During Your
PregnancyEdinburgh, United Kingdom: Health
Education Board for Scotland, 2002.
PERIODICALS

Graves, J. Christopher, et al. ‘‘Maternal Serum Triple
Analyte Screening in Pregnancy.’’American Family
Physician (March 1, 2002): 915-921.
3794

Definition
Tropical spastic paraparesis (TSP) is an incurable
viral infection of the spinal cord that causes weakness
in the legs. It is caused by the human T-cell lymphotropic virus-1 (HTLV-1) retrovirus.

Description
As the name implies, tropical spastic paraparesis
usually occurs in tropical locales. Although isolated
cases have been diagnosed in the southeastern United
States and other places in the United States, TSP is
most frequently found in:


the Caribbean



Japan



the Seychelles Islands



regions of South America



western Africa

TSP usually affects adults between the ages of 30
and 40, and is far more common in women than in
men.
The disease may remain undetected for years after
infection is contracted. When the immune system’s
response to the virus causes nerve damage, the legs
gradually lose strength and flexibility.

Causes and symptoms
TSP is caused by the HTLV-1 virus, which also
causes leukemia. The virus can be spread through the
GALE ENCYCLOPEDIA OF MEDICINE

Retrovirus—A family of RNA viruses containing a
reverse transcriptase enzyme which allows the
viruses’ genetic information to become part of the
genetic information of the host cell upon
replication.
Virus—A microorganism, smaller than bacteria,
which can only replicate within the a cell of a living
plant or animal. The virus provides the genetic
code and the host cell provides the energy and
raw materials for replication.

Troponins test

Prognosis

KEY TERMS

As noted, TSP cannot be cured.

Prevention
The United States Food and Drug Administration
(FDA) has approved screening procedures developed
to detect HTLV-1 in donated blood and blood products
designated for transfusion. These procedures, which can
also be used to diagnose patients with TSP, are designed
to prevent the spread of the disease.
Resources
OTHER

placenta, and also through blood transfusions, breastfeeding, contaminated needles, and sexual contact.
Symptoms may begin years after infection. In
response to the infection, the body’s immune response
may injure nerve tissue, causing symptoms that
include bladder abnormalities, leg pain, loss of feeling
in the feet, tingling sensations, and unpleasant sensations when the skin is touched.

‘‘Current Trends Licensure of Screening Tests for Antibody
to Human T-Lymphotropic Virus Type I.’’ Centers for
Disease Control. May 27, 1998. <http://www.cdc.gov/
epo/mmwr/preview/mmwrhtml/00001311.htm>.

Maureen Haggerty

Tropical sprue see Malabsorption syndrome

As many as 20% of patients with TSP may also
experience:


deafness



double vision



the tendency to incorrectly estimate the amount of
motion necessary to accomplish a specific task
(dysmetria)



exaggerated reflexes



facial paralysis



tremor.

Diagnosis
Infectious disease specialists use blood tests and
magnetic resonance imaging (MRI) of the spinal cord
to diagnose this condition.

Treatment
While the disease is incurable, significant improvement has been reported in the condition of TSP patients
treated with corticosteroids. These drugs are believed to
alleviate symptoms by suppressing the immune system’s response to the virus that causes them.
Plasmapheresis, a dialysis-like procedure in which
symptom-producing antibodies are removed from the
blood, also provides temporary relief.
GALE ENCYCLOPEDIA OF MEDICINE

Troponins test
Definition
Troponins are specific proteins found in heart
muscle. Troponin testing is done to diagnose heart
attacks (myocardial infarctions).

Purpose
When heart muscle is damaged, as in a myocardial
infarction (MI), troponins leak out of cells and into
the bloodstream. Increased troponin levels indicate
myocardial infarction or injury in a person with chest
pain or pressure. Some MIs are silent, manifesting few
if any symptoms.
If infarction is ruled out in a person with continuing or recurring chest pain (unstable angina), an
increased troponin level indicates the person has
heart muscle ischemia (a decreased supply of oxygenated blood to the body), and is at an increased risk
for a future serious heart event.

Description
Although troponins also exist in other muscles,
those in the heart are unique, and are measured separately in laboratory tests. Troponins in the heart are
3795

Tubal ligation

called cardiac troponins. There are two main types of
cardiac troponins; T and I. T is also referred to as
cTnT, while I is also referred to as cTnI.
Both troponin T and I are cardiac markers used to
diagnose myocardial infarctions. Cardiac markers are
substances whose blood levels increase after a myocardial infarction. Others include CK (creatine kinase),
myoglobin, and CK-MB (one of three CK isoenzymes).
Like all cardiac markers, troponins have a unique
diagnostic window (the timeline during which the marker rises, peaks, and returns to normal). Troponin
levels rise within four to six hours after the beginning
of chest pain or heart damage, and stay elevated for at
least one week. This long elevation allows detection of
a myocardial infarction that occurred days earlier, but
prevents detection of a second infarction if it occurred
only days after the first.
Troponins I and T are considered superior cardiac
markers for several reasons. The most significant is
that cardiac troponins are the only markers specific
for heart muscle. Other markers also increase following damage to other muscles. Troponin levels help
predict the extent of heart muscle damage; higher
levels are associated with increased damage, lower
levels with less damage. Levels in a healthy person
are negligible, so an increase is easily detected.
The main difference between troponins I and T is
that cardiac troponin I tests measure only cardiac troponin; tests for cardiac troponin T may cross-react with
troponin found in other muscles and give positive or
increased results in the absence of heart damage.
Two types of tests for troponins T and I are available: a traditional quantitative test that provides an
actual measurement of troponin, and a newer qualitative test that simply reports the result as positive or
negative. The quantitative test takes 45–90 minutes,
and helps distinguish between myocardial infarction
and unstable angina. The qualitative test takes 15
minutes and is used in emergency rooms in which
rapid patient care decisions can be made based on
the presence or absence of troponins.

Preparation

KEY TERMS
Angina—A temporary chest pain caused by the
heart not receiving enough oxygen.
Cardiac marker—A substance in the blood whose
level rises following a myocardial infarction.
Myocardial infarction—Commonly known as a
heart attack, a myocardial infarction is an episode
in which some of the heart’s blood supply is
severely cut off or restricted, causing the heart
muscle to suffer and die from lack of oxygen.

bruising. Warm packs to the puncture site relieve
discomfort.

Normal results
People without heart damage have troponin levels
less than 0.5 ng/mL.

Abnormal results
Levels greater than 2.0 ng/mL indicate a person
has had a significant myocardial injury, such as an
infarction, and is at an increased risk for future serious
heart events. Levels between 0.5 and 2.0 ng/mL indicate a diagnosis of unstable angina, other heart disorders, or chronic kidney failure.
Resources
BOOKS

Wu, Alan, editor. Cardiac Markers. Washington, DC:American
Association of Clinical Chemistry (AACC) Press,1998.

Nancy J. Nordenson

Trypanosoma cruzi infection see Chagas’
disease
TSS see Toxic shock syndrome
Tsutsugamushi fever see Scrub typhus

Troponins tests require 5 mL of blood. Collection
of the sample takes only a few minutes.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops reduces
3796

Tubal ligation
Definition
Tubal ligation is a permanent voluntary form of
birth control (contraception) in which a woman’s
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
Tubal ligation is performed in women who definitely want to prevent future pregnancies. It is frequently chosen by women who do not want more
children, but who are still sexually active and potentially fertile, and want to be free of the limitations of
other types of birth control. Women who should not
become pregnant for health concerns or other reasons
may also choose this birth control method. Tubal
ligation is one of the leading methods of contraception, having been chosen by over 10 million women in
the United States–about 15% of women of reproductive age. The typical tubal ligation patient is over age
30, is married, and has had two or three children.

Precautions
Tubal ligation should be postponed if the woman
is unsure about her decision. While it is sometimes
reversible, the procedure should be considered permanent and irreversible. Up to 10% of sterilized women
regret having had the surgery, and about 1% seek
treatment in attempts to restore fertility.

Description
Tubal ligation, or getting one’s ‘‘tubes tied,’’ refers
to female sterilization, the surgery that ends a
woman’s ability to conceive. The operation is performed on the patient’s Fallopian tubes. These tubes,
which are about 10 cm long and 0.5 cm in diameter, are
found on the upper outer sides of the uterus, and open
into the uterus through small channels. It is within the
Fallopian tube that fertilization, the joining of the egg
and the sperm, takes place. During tubal ligation, the
tubes are cut or blocked in order to close off the
sperm’s access to the egg.
Normally, tubal ligation takes about 20–30 minutes, and is performed under general anesthesia, spinal
anesthesia, or local anesthesia with sedation. The surgery can be performed on either hospitalized patients
within 24 hours after childbirth or on outpatients. The
woman can usually leave the hospital the same day.
The most common surgical approaches to tubal
ligation include laparoscopy and mini-laparotomy. In
a laparoscopic tubal ligation, a long, thin telescopelike surgical instrument called a laparoscope is
inserted into the pelvis through a small cut about 1 cm
long near the navel. Carbon dioxide gas is pumped in to
help move the abdominal wall to give the surgeon easier
GALE ENCYCLOPEDIA OF MEDICINE

access to the tubes. Often the surgical instruments are
inserted through a second incision near the pubic-hair
line. An instrument may be placed through the vagina
to hold the uterus in place.
In a mini-laparotomy, a 3–4 cm incision is made just
above the pubic bone or under the navel. A larger incision, or laparotomy, is rarely used today. Tubal ligation
can also be performed at the time of a cesarean section.
Tubal ligation costs about $2,000 when performed
by a private physician, but is less expensive when
performed at a family planning clinic. Most insurance
plans cover treatment costs.
Tubal ligation is performed in several ways:


Electrocoagulation. A heated needle connected to an
electrical device is used to cauterize or burn the tubes.
Electrocoagulation is the most common method of
tubal ligation.



Falope ring. In this technique, an applicator is
inserted through an incision above the bladder and
a plastic ring is placed around a loop of the tube.



Hulka clip. The surgeon places a plastic clip across a
tube held in place by a steel spring.



Silicone rubber bands. A band placed over a tube
forms a mechanical block to sperm.

Preparation
Preparation for tubal ligation includes patient
education and counseling. Before surgery, it is important that the woman understand the permanent nature
of tubal ligation, and the risks of anesthesia and surgery. Her medical history is reviewed, and a physical
examination and laboratory testing are performed.
The patient is not allowed to eat or drink for several
hours before surgery.

Aftercare
After surgery, the patient is monitored for several
hours before she is allowed to go home. She is
instructed on care of the surgical wound, and what
signs to watch for, such as fever, nausea, vomiting,
faintness, or pain. These signs could indicate that
complications have occurred.

Risks
While major complications are uncommon after
tubal ligation, there are risks with any surgical procedure. Possible side effects include infection and bleeding. Rarely, death may occur as a complication of
general anesthesia if a major blood vessel is cut. The
3797

Tubal ligation

Fallopian tubes are surgically cut or blocked off to
prevent pregnancy.

Tubal ligation

Fallopian tubes

Ovary
Uterus
Cervix

Vagina

Tubal ligation is a permanent form of contraception in which a woman’s Fallopian tubes are surgically cut, cauterized, tied, or
blocked to prevent pregnancy. This procedure blocks the pathway sperm takes to fertilize an egg. (Illustration by Electronic
Illustrators Group.)

KEY TERMS
Contraception—The prevention of the union of the
male’s sperm with the female’s egg.
Ectopic pregnancy—The implantation of a fertilized egg in a Fallopian tube instead of the uterus.
Electrocoagulation—The coagulation or destruction of tissue through the application of a highfrequency electrical current.
Female sterilization—The process of permanently
ending a woman’s ability to conceive by tying off or
cutting apart the Fallopian tubes.
Laparoscopy—Abdominal surgery performed
through a laparoscope, which is a thin telescopic
instrument inserted through an incision near the
navel.

3798

death rate following tubal ligation is about four per
100,000 sterilizations.
After laparoscopy, the patient may experience
pain in the shoulder area from the carbon dioxide
used during surgery, but the technique is associated
with less pain than mini-laparotomy, as well as a faster
recovery period. Mini-laparotomy results in a higher
incidence of pain, bleeding, bladder injury, and infection compared with laparoscopy. Patients normally
feel better after three or four days of rest, and are
able to resume sexual activity at that time.
Following tubal ligation, there is a low risk (less
than 1%) of ectopic pregnancy. Ectopic pregnancy is a
condition in which the fertilized egg implants in a place
other than the uterus, usually in one of the Fallopian
tubes. Ectopic pregnancies are more likely to happen
in younger women, and in women whose tubes were
ligated by electrocoagulation.
GALE ENCYCLOPEDIA OF MEDICINE

After having her tubes ligated, a woman does not
need to use any form of birth control to avoid pregnancy. Tubal ligation is almost 100% effective for the
prevention of conception. The possibility for treatment failure is very low–fewer than one in 200
women (0.4%) will become pregnant during the first
year after sterilization. Failure can happen if the cut
ends of the tubes grow back together; if the tube was
not completely cut or blocked off; if a plastic clip or
rubber band is loose or comes off; or if the woman was
already pregnant at the time of surgery.
Resources
ORGANIZATIONS

American College of Obstetricians and Gynecologists. 409
12th Street, S.W., P.O. Box 96920.
Planned Parenthood Federation of America, Inc. 810
Seventh Ave., New York, NY,10019. (800) 669-0156.
<http://www.plannedparenthood.org>.

Mercedes McLaughlin

Tube compression of the
esophagus and stomach
Definition
Tube compression of the esophagus and stomach
is an emergency procedure used to stop bleeding from
the upper digestive tract.

Purpose
Vomiting blood is both frightening and life-threatening. Among its causes are:


bleeding from the nose and throat



peptic ulcers



stomach cancer



esophageal cancer



a tear in the esophagus caused by violent vomiting
(Mallory-Weiss syndrome)



breaking of blood vessels in the esophagus.

The most profuse bleeding comes from veins in the
lower esophagus, just above the stomach, that have
dilated to enormous dimensions as the result of liver
disease. When the liver shrinks due to cirrhosis (scarring
from chronic disease), its blood vessels shrink, forcing
GALE ENCYCLOPEDIA OF MEDICINE

blood from the intestines to find alternate routes back
to the heart. The blood usually flows through tiny veins
in the esophagus located just beneath the passageway
where food passes downward and vomitus passes
upward. Major causes for this rearrangement are alcoholic liver disease, chronic hepatitis, and cholangitis.
Called esophageal varices, the affected veins can be
easily damaged and bleed voraciously.

Description
One emergency method of stopping bleeding from
esophageal varices is to tamponade it with a balloon.
The Sengstaken-Blakemore tube is a complex rubber
device with two balloons and three channels—one
channel for each balloon and one that goes all the
way through. The Minnesota tube has four channels,
an extra one that opens above the first balloon. The
bottom balloon is round; the upper balloon is long and
narrow. The tube is passed through the nose or mouth
into the stomach, where the bottom balloon is inflated.
Then the tube is pulled back until the bottom balloon
comes up against the narrow valve at the top of the
stomach, when it can go no further. At this point, the
upper balloon is inflated, putting pressure on a length
of esophagus where the bleeding veins are located. The
tube is then fixed so it cannot be dislodged. The third
channel in the tube is used to aspirate (suck out)
stomach contents to see if the bleeding has stopped.
The fourth channel aspirates from the esophagus.
These tubes are a temporary measure. They stabilize the patient until bleeding has stopped, blood
transfusions are received, and permanent repair is
imminent.
Since the lower balloon effectively separates the
esophagus from the stomach, it is possible to determine more accurately where the bleeding is located
when it is in place.
This method of treating upper intestinal bleeding
is being replaced by procedures that use a gastroscope,
a flexible device that permits viewing and operating
without surgery.

Preparation
The procedure is explained to the patient and
family. A sedative may be given to prepare the patient
for the procedure.

Aftercare
With the tube in place, the patient cannot eat and
may have some difficulty breathing. The patient will
be hospitalized until the tube can be removed.
3799

Tube compression of the esophagus and stomach

Normal results

Tube feedings

Precautions

KEY TERMS
Cholangitis—Inflammation of the system of tubes
that drains bile from the liver into the intestines.
Chronic hepatitis—Long lasting inflammation of
the liver due to viruses or other causes.
Peptic ulcers—Wounds in the stomach and duodenum caused by stomach acid and the bacterium
Helicobacter pylori.

Risks
Major complications frequently occur, and death
results about 3% of the time. Problems include
damage to the esophagus and stomach and interference with the airway. Should the tube remain in place
too long, there is danger of the pressure eroding the
esophagus or the nose.
Resources
BOOKS

Henneman, Philip L. ‘‘Gastrointestinal bleeding.’’ In
Emergency Medicine, edited by Peter Rosen, et al. St.
Louis: Mosby, 1998.

J. Ricker Polsdorfer, MD

Tube feedings
Definition
Nutrients, either a special liquid formula or
pureed food, are delivered to a patient through a
tube directly into the gastrointestinal tract, usually
into the stomach or small intestine.

Purpose
Tube feeding provides nutrition to patients who
are unable or unwilling to eat food. Conditions where
tube feeding is considered include protein-energy malnutrition, liver or kidney failure, coma, or in patients
who cannot chew or swallow (dysphagia) due to
stroke, brain tumor, or head injury. Patients who are
receiving radiation therapy or chemotherapy treatments for cancer may also be candidates for tube
feedings.
3800

Certain medications may interact with some formulas to inactivate the nutrients or change the way
that the drug is absorbed.

Description
A flexible, narrow tube is inserted into some portion of the digestive tract and liquid formulas or liquefied foods are placed into the tube to meet the patient’s
nutritional needs. The feeding may be pumped into the
tube or allowed to drip into the tube continuously or at
scheduled feeding times.
A feeding tube can be inserted by a surgical or
nonsurgical procedure in several positions along the
gastrointestinal tract. The tube may be inserted into
the nose and passed down the throat and through the
esophagus. A nasogastric tube is inserted through the
nose with the end of the tube reaching into the stomach.
A nasoduodenal or nasojejunal tube is inserted through
the nose and ends in either the duodenum or jejunum,
both of which are portions of the small intestine. This
type of tube placement is usually used for short-term
feeding. Surgical placement of a feeding tube may be
done if there will be a long-term need for feeding that
bypasses the upper digestive tract. An esophagostomy
creates an opening in the esophagus, a gastrostomy
creates an opening into the stomach, and a jejunostomy
creates an opening into the jejunum. The feeding tube is
then inserted through the surgically created opening.
Tube feedings can be a mixture of regular foods
that are blended with liquid to make a consistency that
will pass through the tube. Nutritionally balanced
liquid products are often more convenient to use and
ensure a balance of proteins, fats, and carbohydrates
along with vitamins and minerals. Specialized formulas
are also available to meet almost any nutritional need.
For example, patients with severe burns, proteinenergy malnutrition, or slow wound healing may
require formulas that are higher in protein. Patients
with renal failure may require low-protein formulas
with lower concentrations of minerals and vitamins.

Preparation
The reasons that tube feeding is necessary are
discussed with the patient, as is the length of time
that the feeding tube is expected to be in place. The
specific procedure is also explained to the patient.

Aftercare
Patients with ostomy feeding tubes may have the
tube positioned level with the surrounding skin. A cap
GALE ENCYCLOPEDIA OF MEDICINE

Tube feedings

Enteral
feeding
container

Enteral
feeding
pump

8 Fr. feeding tube
Flexible weighted tip
A feeding tube can be inserted by a surgical or nonsurgical procedure in several positions along the gastrointestinal tract to
provide nutrition to patients who are unable or unwilling to eat food. The feeding may be pumped into the tube or allowed to drip
into the tube continuously, or at scheduled feeding times. The illustration above features a nasojejunal tube which is inserted
through the nose and ends in either the duodenum or jejunum. (Illustration by Electronic Illustrators Group.)

Risks

KEY TERMS
Duodenum—The upper portion of the small intestine. It is approximately 10 in (25 cm) long and
extends from the stomach to the jejunum.
Jejunum—The middle portion of the small intestine. It is approximately 8 ft (2.5 m) long and
extends from the jejunum to the ileum.

or button can be placed over the opening so that it can
be more comfortably concealed under clothing. The
opening and surrounding tissue need to be cleaned and
inspected regularly to prevent infection. For patients
with a tube inserted through the nose, daily nasal
hygiene is important and the mouth and lips should
be kept moist. Good mouth care is necessary for any
patient with a feeding tube.
GALE ENCYCLOPEDIA OF MEDICINE

Formula from the tube can back up in the esophagus and be breathed into the trachea and lungs, causing
aspiration pneumonia. The placement of the tube
should be checked frequently and the head of the bed
elevated during and after feeding to prevent the solution from moving back up the digestive tract. Feeding
tubes can also become clogged and should be flushed
regularly with water. If the feeding formula is too concentrated or given too fast, the patient may experience
nausea, vomiting, cramping, and bloating. The feeding
may need to be diluted with liquid or the rate at which it
is given decreased. Diarrhea or constipation can occur if
the feeding is not the right composition or does not
provide enough liquid. The tube itself can irritate the
nasal passage, esophagus, or surrounding tissues.

Normal results
A patient may be able to return to a normal diet of
solid foods after short-term supplementation with
3801

Tuberculin skin test

formula through a feeding tube. In cases where longterm nutritional therapy is required, all of the patient’s
nutritional needs will have to be provided by the formula. The balance of fluids, calories, proteins, fats,
vitamins, and minerals may need to be adjusted
periodically.

Abnormal results
If formula feedings are not tolerated by the patient
or are inadequate to meet his or her nutritional needs,
the patient may need to receive nutrition through an
intravenous line (parenteral nutrition). This type of
therapy involves delivery of sterile nutrient solutions
directly into the bloodstream through a needle
inserted into a vein.
Resources
BOOKS

Howard, Lyn. ‘‘Enteral and Parenteral Nutrition Therapy.’’
InHarrison’s Principles of Internal Medicine, edited by
Anthony S. Fauci, et al. New York:McGraw-Hill, 1997.

particularly for those individuals seeking employment
in the health care or food service professions.
People can be exposed to or infected with TB
without showing any symptoms or necessarily developing the disease. Individuals with normally functioning immune systems generally prevent the spread of
the bacteria by ‘‘walling off’’ or encysting the bacteria
within the body. To be at risk for infection a person
must have or had close contact with someone who has
active tuberculosis (such as a friend or family member). Persons who are more at risk for developing the
TB infection overtly include those with a weakened
immune system (immunocompromised), either from a
chronic disease, such as HIV infection; or as a result of
a tissue or organ transplant or other medical treatment
designed to suppress the immune system. In addition,
persons who are heavy users of crack cocaine or alcohol are more susceptible to TB than those who do not
abuse these substances. Symptoms of tuberculosis
include a persistent cough, fever, weight loss, night
sweats, fatigue, and loss of appetite.

Precautions

Altha Roberts Edgren

Tuberculin skin test
Definition
Tuberculosis (TB) is an airborne infectious disease
caused by the bacteria Mycobacterium tuberculosis.
Besides culturing in the laboratory, the two most common types of tests to screen for exposure to this disease
are the Mantoux PPD tuberculin skin test, which is
generally considered more reliable, and the older TB
tine test, which is now rarely used. These tests are
designed to help identify individuals who may have
been infected by the tuberculosis bacteria. A diagnosis
of active, infectious tuberculosis is never made solely
based on the results of a TB skin test, but requires further
testing, including a sputum culture and a chest x-ray.

Purpose
Because TB is spread through the air, especially in
poorly ventilated areas, it is more commonly found
among people living in crowded conditions, such as
jails, nursing homes, and homeless shelters. Often, a
TB skin test will be given as part of a physical examination when a person is hiring a new employee,
3802

Although the test is generally considered safe, it is
important to inform the person conducting the test if
the patient may be pregnant, has had a positive TB test
in the past, or has had tuberculosis in the past. People
who have had a positive TB test in the past will probably always have a positive test and should not be
tested again.
There are several situations when the TB test
results might not be accurate. These include situations
involving people who:


have had vaccinations (such as those for measles,
polio, rubella or mumps) within the last four weeks



are taking steroids



have severe malnutrition

Description
TB skin tests are usually given at a clinic, hospital,
or doctor’s office. Sometimes the tests are given at
schools or workplaces and may be a pre-employment
requirement. Many cities provide free TB skin tests
and followup care. The Mantoux PPD tuberculin skin
test involves injecting a very small amount of a substance called PPD tuberculin just under the top layer
of the skin (intracutaneously). Tuberculin is a mixture
of antigens obtained from the culture of M. tuberculosis. Antigens are foreign particles or proteins that
stimulate the immune system to produce antibodies.
GALE ENCYCLOPEDIA OF MEDICINE

After 48–72 hours, the test site will be examined
by a trained person for evidence of swelling. People
who have been exposed to tuberculosis will develop
an immune response, causing a slight swelling at the
injection site. If there is a lump or swelling, the health
care provider will use a ruler to measure the size of
the reaction. Some public health physicians recommend using a 72-hour waiting period as a general
practice on the grounds that a 48-hour waiting period yields a higher percentage of false negative test
results.
The other method of TB skin test is called the
multiple puncture test or tine test because the small
test instrument has several small tines that lightly prick
the skin. The small points of the instrument are either
coated with dried tuberculin or are used to puncture
through a film of liquid tuberculin. The test is read by
measuring the size of the largest papule. Because it is
not possible to precisely control the amount of tuberculin used in the tine test, a positive test should be
verified using the Mantoux test. For this reason, the
tine test is not as widely used as the Mantoux test and
is considered to be less reliable; as of 2000, it is no
longer recommended for general use.

Preparation
There is no special preparation needed before a
TB skin test. A brief personal history will be taken to
determine whether the person has had tuberculosis or
a TB test before, has been in close contact with anyone
with TB, or has any significant risk factors. Directly
before the test, the skin on the arm at the injection site
is usually cleaned with an alcohol swab and allowed to
air dry.

Risks
The risk of an adverse reaction is very low.
Occasionally, an individual who has been exposed to
the TB bacteria will develop a large reaction in which
the arm swells and is uncomfortable. This reaction
should disappear in two weeks. A sore might develop
where the injection was given, or a fever could occur,
but these are extremely rare reactions.
It is possible that a person who has TB may
receive a negative test result (called a ‘‘false negative’’)
or a person who does not have TB may receive a
positive test result (called a ‘‘false positive’’). If there
is some doubt, the test may be repeated or the person
may be given a diagnostic test using a chest x ray and/
or sputum sample culture test to determine whether
the disease is present and/or active in the lungs.

Normal results
In people who have not been exposed to TB, there
will be little or no swelling at the test site after 48–72
hours. This is a negative test result. Negative test results
can be interpreted to mean that the person has not been
infected with the tuberculosis bacteria or that the person has been infected recently and not enough time has
elapsed for the body to react to the skin test. Persons
become sensitive between two and ten weeks after the
initial infection. As a result, if the person has been in
contact with someone with tuberculosis, the test should
be repeated in three months. Also, because it may take
longer than 72 hours for an elderly individual to
develop a reaction, it may be useful to repeat the TB
skin test after one week to adequately screen these
individuals. Immunocompromised persons may be
unable to react sufficiently to the Mantoux test, and
either a chest x ray or sputum sample may be required.
A newer test that appears to be preferable to the
tuberculin skin test in evaluating patients who are
HIV-positive is the enzyme-linked immunospot
(ELISPOT) assay. A group of researchers in the
United Kingdom found that the ELISPOT assay was
more accurate than the PPD test in detecting active as
well as latent tuberculosis in HIV-positive patients.

Aftercare
After having a TB skin test, it is extremely important to make sure that the patient keeps the appointment to have the test reaction read. The patient is
instructed to keep the test site clean, uncovered, and
to not scratch or rub the area. Should severe swelling,
itching, or pain occur, or if the patient has trouble
breathing, the clinic or health care provider should
be contacted immediately.
GALE ENCYCLOPEDIA OF MEDICINE

Abnormal results
A reaction of 5 mm of induration (swelling) is
considered positive for the following groups:


household contacts
tuberculosis

of

persons

with

active



AIDS patients



persons with old healed tuberculosis on chest x ray
3803

Tuberculin skin test

Two different tuberculin preparations are available,
Old Tuberculin (OT) and Purified Protein Derivative
(PPD). The latter is the preferred testing substance.
The test is usually given on the inside of the forearm
about halfway between the wrist and the elbow, where
a small bubble will form as the tuberculin is injected.
The skin test takes just a minute to administer.

Tuberculin skin test



KEY TERMS
Antibody—A specific protein produced by the
immune system in response to a specific foreign
protein or particle called an antigen.
Antigen—Any foreign particle or protein that
causes an immune response.
Attenuated—Alive but weakened; an attenuated
microorganism can no longer produce disease.
Cross-reaction—A positive reaction that occurs as
a result of a person’s exposure to other non-tuberculosis bacteria.
Immunocompromised—A state in which the
immune system is suppressed or not functioning
properly.
Induration—An abnormally hard spot or area on
the skin. The tuberculin skin test produces an
induration at the test site in persons who have
been exposed to TB.
Intracutaneous—Into the skin, in this case directly
under the top layer of skin.
Mantoux or PPD test—Other names for a tuberculin
skin test. PPD stands for purified protein derivative.
Tuberculin—A mixture of antigens obtained from
the cultured bacteria that cause tuberculosis,
Mycobacterium tuberculosis.



organ transplant recipients.



persons receiving immunosuppressive medications

A reaction of 10 mm of induration is considered
positive in individuals with one or more of the following risk factors which are either reasons to have a
higher exposure to TB and/or a condition that
increases the risk for progression to active TB:


foreign-born immigrants from Asia, Africa, or Latin
America



injection drug users and persons who abuse alcohol



residents and employees of such high-risk congregate
settings as hospitals, homeless shelters, and jails



medically under-served low income populations



TB laboratory personnel



children younger than four years of age or infants,
children or adolescents exposed to adults in high risk
categories



residents of long-term care facilities

3804

individuals with certain medical conditions that
increase the risk of developing tuberculosis; these
medical conditions include being 10% or more
below ideal body weight, silicosis, chronic renal failure, diabetes mellitus, high dose corticosteroid or
other immunosuppressive therapy, some blood disorders like leukemia and lymphomas, and other
cancer

Finally, a reaction of 15 mm of induration or
greater is considered positive in those with no risk
factors and are therefore at the lowest risk of developing TB.
A TB skin conversion is defined as an increase of
10 mm or greater of induration within a two year
period, regardless of age.
A positive reaction to tuberculin may be the result
of a previous natural infection with M. tuberculosis,
infection with a variety of non-tuberculosis mycobacteria (cross-reaction), or tuberculosis vaccination with
a live, but weakened (attenuated) mycobacterial
strain. TB vacination is not done in the US. Crossreactions are positive reactions that occur as a result of
a person’s exposure to other non-tuberculosis bacteria. These tend to be smaller than those caused by
M. tuberculosis. There is no reliable way of distinguishing whether a positive TB skin test is due to a
previous vaccination against tuberculosis. Generally,
however, positive results are not due to vaccination
exposure because reactions in vaccinated people tend
to be less than 10 mm, and an individual’s sensitivity to
tuberculin steadily declines after vaccination. If the
skin test is interpreted as positive, a chest x ray will
be performed to determine whether the person has
active tuberculosis or whether the body has sufficiently handled the infection.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Infectious Diseases Caused by Mycobacteria.’’ In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Centers for Disease Control (CDC). ‘‘Targeted Tuberculin
Testing and Treatment of Latent Tuberculosis
Infection.’’ Morbidity and Mortality Weekly Report 49,
RR-6 (2000): 3–4.
Chapman, A. L., M. Munkanta, K. A. Wilkinson, et al.
‘‘Rapid Detection of Active and Latent Tuberculosis
Infection in HIV-Positive Individuals by Enumeration
of Mycobacterium tuberculosis-Specific T Cells.’’ AIDS
16 (November 22, 2002): 2285–2293.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Lung Association. (800) LUNG-USA.
Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
National Heart, Lung, and Blood Institute (NHLBI). P. O.
Box 30105, Bethesda, MD 20824-0105. (301) 592-8573.
<www.nhlbi.nih.gov>.
National Tuberculosis Center. University of Medicine and
Dentistry of New Jersey. Executive Office, Suite GB1,
65 Bergen Street, Newark, NJ 07107-3268. (800)
4TB-DOCS. <http://www.umdnj.edu/ntbcweb/
ntbchome.htm>.
OTHER

American Academy of Family Physicians. ‘‘Positive Skin
Tests for Tuberculosis.’’ <http://www.aafp.org/
healthinfo>.
‘‘Diagnostic Standards and Classification of Tuberculosis.’’
<http://aepo-xdv-www.epo.cdc.gov/wonder/prevguid/p0000425/body006.htm>.
U.S. Department of Health and Human Services Public
Health Service, Centers for Disease Control and
Prevention. ‘‘Questions and Answers About TB.’’
<http://www.cdc.gov/nchstp/tb/faq.htm>.

Suzanne M. Lutwick, MPH
Rebecca J. Frey, PhD

Tuberculosis
Definition
Tuberculosis (TB) is a potentially fatal contagious
disease that can affect almost any part of the body but
is mainly an infection of the lungs. It is caused by a
bacterial microorganism, the tubercle bacillus or
Mycobacterium tuberculosis. Although TB can be treated, cured, and can be prevented if persons at risk take
certain drugs, scientists have never come close to wiping it out. Few diseases have caused so much distressing illness for centuries and claimed so many lives.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Overview
Tuberculosis was popularly known as consumption for a long time. Scientists know it as an infection
caused by M. tuberculosis. In 1882, the microbiologist Robert Koch discovered the tubercle bacillus, at
a time when one of every seven deaths in Europe was
caused by TB. Because antibiotics were unknown, the
only means of controlling the spread of infection was
to isolate patients in private sanitoria or hospitals
limited to patients with TB—a practice that continues to this day in many countries. The net effect
of this pattern of treatment was to separate the study
of tuberculosis from mainstream medicine. Entire
organizations were set up to study not only the disease as it affected individual patients, but its impact
on the society as a whole. At the turn of the twentieth
century more than 80% of the population in the
United States were infected before age 20, and tuberculosis was the single most common cause of death.
By 1938 there were more than 700 TB hospitals in this
country.
Tuberculosis spread much more widely in Europe
when the industrial revolution began in the late nineteenth century. The disease became widespread somewhat later in the United States, because the movement
of the population to large cities made overcrowded
housing so common. When streptomycin, the first
antibiotic effective against M. tuberculosis, was discovered in the early 1940s, the infection began to
come under control. Although other more effective
anti-tuberculosis drugs were developed in the following decades, the number of cases of TB in the United
States began to rise again in the mid-1980s. This
upsurge was in part again a result of overcrowding
and unsanitary conditions in the poor areas of large
cities, prisons, and homeless shelters. Infected visitors
and immigrants to the United Stateshave also contributed to the resurgence of TB. An additional factor is
the AIDS epidemic. AIDS patients are much more
likely to develop tuberculosis because of their weakened immune systems. There still are an estimated 8–
10 million new cases of TB each year worldwide, causing roughly 3 million deaths.
High-risk populations
THE ELDERLY. Tuberculosis is more common in
elderly persons. More than one-fourth of the nearly
23,000 cases of TB reported in the United States in
1995 developed in people above age 65. Many elderly
patients developed the infection some years ago when

3805

Tuberculosis

Howard, A. A., R. S. Klein, E. E. Schoenbaum, and
M. N. Gourevitch. ‘‘Crack Cocaine Use and Other Risk
Factors for Tuberculin Positivity in Drug Users.’’
Clinical Infectious Diseases 35 (November 15, 2002):
1183–1190.
Kong, P. M., J. Tapy, P. Calixto, et al. ‘‘Skin-Test Screening
and Tuberculosis Transmission Among the Homeless.’’
Emerging Infectious Diseases 8 (November 2002):
1280–1284.
Singh, D., C. Sutton, and A. Woodcock. ‘‘Tuberculin Test
Measurement: Variability Due to the Time of
Reading.’’ Chest 122 (October 2002): 1299–1301.

Tuberculosis

F L O R E N C E B . S E I B E R T (1897–1991)
in Baltimore, where she studied chemistryand zoology.
She graduated in 1918, then worked under the direction
of one of her chemistry teachers, Jessie E. Minor, at the
Chemistry Laboratory of the Hammersley Paper Mill in
Garfield, New Jersey. She and her professor, having
responded to the call for women to fill positions vacated
by men fighting in World War I, coauthored scientific
papers on the chemistry of cellulose and wood pulps.

(Library of Congress.)

Florence Barbara Seibert was born on October 6, 1897,
in Easton, Pennsylvania, the second of three children. She
was the daughter of George Peter Seibert, a rug manufacturer and merchant, and Barbara (Memmert) Seibert. At the
age of three she contracted polio. Despite her resultant
handicaps, she completed high school, with the help of
her highly supportive parents, and entered Goucher College

the disease was more widespread. There are additional
reasons for the vulnerability of older people: those
living in nursing homes and similar facilities are in
close contact with others who may be infected. The
aging process itself may weaken the body’s immune
system, which is then less able to ward off the tubercle
bacillus. Finally, bacteria that have lain dormant for
some time in elderly persons may be reactivated and
cause illness.
RACIAL AND ETHNIC GROUPS. TB also is more
common in blacks, who are more likely to live under
conditions that promote infection. At the beginning of
the new millennium, two-thirds of all cases of TB in
the United States affect African Americans,
Hispanics, Asians, and persons from the Pacific
Islands. Another one-fourth of cases affect persons
born outside the United States. As of 2002, the risk
of TB is still increasing in all these groups.

As of late 2002, TB is a major health problem in
certain specific immigrant communities, such as the
3806

A biochemist who received her Ph.D. from Yale
University in 1923, Florence B. Seibert is best known for
her research in the biochemistry of tuberculosis. She developed the protein substance used for the tuberculosis skin test.
The substance was adopted as the standard in 1941 by the
United States and a year later by the World Health
Organization. In addition, in the early 1920s, Seibert discovered that the sudden fevers that sometimes occurred during
intravenous injections were caused by bacteria in the distilled water that was used to make the protein solutions. She
invented a distillation apparatus that prevented contamination. This research had great practical significance later when
intravenous blood transfusions became widely used in surgery. Seibert authored or coauthored more than a hundred
scientific papers. Her later research involved the study of
bacteria associated with certain cancers. Her many honors
include five honorary degrees, induction into the National
Women’s Hall of Fame in Seneca Falls, New York (1990), the
Garvan Gold Medal of the American Chemical Society
(1942), and the John Elliot Memorial Award of the
American Association of Blood Banks (1962).

Vietnamese in southern California. One team of public
health experts in North Carolina maintains that treatment for tuberculosis is the most pressing health care
need of recent immigrants to the United States. In
some cases, the vulnerability of immigrants to tuberculosis is increased by occupational exposure, as a
recent outbreak of TB among Mexican poultry farm
workers in Delaware indicates. Other public health
experts are recommending tuberculosis screening at
the primary care level of all new immigrants and
refugees.
LIFESTYLE FACTORS. The high risk of TB in AIDS
patients extends to those infected by human immunodeficiency virus (HIV) who have not yet developed
clinical signs of AIDS. Alcoholics and intravenous
drug abusers are also at increased risk of contracting
tuberculosis. Until the economic and social factors
that influence the spread of tubercular infection are
remedied, there is no real possibility of completely
eliminating the disease.

GALE ENCYCLOPEDIA OF MEDICINE

Transmission
Tuberculosis spreads by droplet infection. This
type of transmission means that when a TB patient
exhales, coughs, or sneezes, tiny droplets of fluid containing tubercle bacilli are released into the air. This
mist, or aerosol as it is often called, can be taken into
the nasal passages and lungs of a susceptible person
nearby. Tuberculosis is not, however, highly contagious compared to some other infectious diseases.
Only about one in three close contacts of a TB patient,
and fewer than 15% of more remote contacts, are
likely to become infected. As a rule, close, frequent,
or prolonged contact is needed to spread the disease.
Of course, if a severely infected patient emits huge
numbers of bacilli, the chance of transmitting infection is much greater. Unlike many other infections, TB
is not passed on by contact with a patient’s clothing,
bed linens, or dishes and cooking utensils. The most
important exception is pregnancy. The fetus of an
infected mother may contract TB by inhaling or swallowing the bacilli in the amniotic fluid.
Progression
Once inhaled, tubercle bacilli may reach the small
breathing sacs in the lungs (the alveoli), where they are
taken up by cells called macrophages. The bacilli multiply within these cells and then spread through the
lymph vessels to nearby lymph nodes. Sometimes the
bacilli move through blood vessels to distant organs.
At this point they may either remain alive but inactive
(quiescent), or they may cause active disease. Actual
tissue damage is not caused directly by the tubercle
bacillus, but by the reaction of the person’s tissues to
its presence. In a matter of weeks the host develops an
immune response to the bacillus. Cells attack the
bacilli, permit the initial damage to heal, and prevent
future disease permanently.
Infection does not always mean disease; in fact, it
usually does not. At least nine of ten patients who
harbor M. tuberculosis do not develop symptoms or
physical evidence of active disease, and their x-rays
remain negative. They are not contagious; however,
they do form a pool of infected patients who may get
sick at a later date and then pass on TB to others. It is
thought that more than 90% of cases of active tuberculosis come from this pool. In the United States this
group numbers 10–15 million persons. Whether or not
a particular infected person will become ill is impossible to predict with certainty. An estimated 5% of
infected persons get sick within 12–24 months of
GALE ENCYCLOPEDIA OF MEDICINE

being infected. Another 5% heal initially but, after
years or decades, develop active tuberculosis either in
the lungs or elsewhere in the body. This form of the
disease is called reactivation TB, or post-primary disease. On rare occasions a previously infected person
gets sick again after a later exposure to the tubercle
bacillus.
Pulmonary tuberculosis
Pulmonary tuberculosis is TB that affects the
lungs. Its initial symptoms are easily confused with
those of other diseases. An infected person may at
first feel vaguely unwell or develop a cough blamed
on smoking or a cold. A small amount of greenish or
yellow sputum may be coughed up when the person
gets up in the morning. In time, more sputum is produced that is streaked with blood. Persons with pulmonary TB do not run a high fever, but they often
have a low-grade one. They may wake up in the night
drenched with cold sweat when the fever breaks. The
patient often loses interest in food and may lose
weight. Chest pain is sometimes present. If the infection allows air to escape from the lungs into the chest
cavity (pneumothorax) or if fluid collects in the pleural
space (pleural effusion), the patient may have difficulty
breathing. If a young adult develops a pleural effusion,
the chance of tubercular infection being the cause is
very high. The TB bacilli may travel from the lungs to
lymph nodes in the sides and back of the neck.
Infection in these areas can break through the skin
and discharge pus. Before the development of effective
antibiotics, many patients became chronically ill with
increasingly severe lung symptoms. They lost a great
deal of weight and developed a wasted appearance.
This outcome is uncommon today—at least where
modern treatment methods are available.
Extrapulmonary tuberculosis
Although the lungs are the major site of damage
caused by tuberculosis, many other organs and tissues
in the body may be affected. The usual progression is
for the disease to spread from the lungs to locations
outside the lungs (extrapulmonary sites). In some
cases, however, the first sign of disease appears outside
the lungs. The many tissues or organs that tuberculosis
may affect include:


Bones. TB is particularly likely to attack the spine
and the ends of the long bones. Children are especially prone to spinal tuberculosis. If not treated, the
spinal segments (vertebrae) may collapse and cause
paralysis in one or both legs.
3807

Tuberculosis

Causes and symptoms

Tuberculosis



Kidneys. Along with the bones, the kidneys are probably the commonest site of extrapulmonary TB.
There may, however, be few symptoms even though
part of a kidney is destroyed. TB may spread to the
bladder. In men, it may spread to the prostate gland
and nearby structures.



Female reproductive organs. The ovaries in women
may be infected; TB can spread from them to the
peritoneum, which is the membrane lining the
abdominal cavity.



Abdominal cavity. Tuberculous peritonitis may
cause pain ranging from the vague discomfort of
stomach cramps to intense pain that may mimic the
symptoms of appendicitis.



Joints. Tubercular infection of joints causes a form of
arthritis that most often affects the hips and knees.
The wrist, hand, and elbow joints also may become
painful and inflamed.



Meninges. The meninges are tissues that cover the
brain and the spinal cord. Infection of the meninges
by the TB bacillus causes tuberculous meningitis, a
condition that is most common in young children but
is especially dangerous in the elderly. Patients
develop headaches, become drowsy, and eventually
comatose. Permanent brain damage is the rule unless
prompt treatment is given. Some patients with tuberculous meningitis develop a tumor-like brain mass
called a tuberculoma that can cause stroke-like
symptoms.



Skin, intestines, adrenal glands, and blood vessels.
All these parts of the body can be infected by
M. tuberculosis. Infection of the wall of the body’s
main artery (the aorta), can cause it to rupture with
catastrophic results. Tuberculous pericarditis occurs
when the membrane surrounding the heart (the pericardium) is infected and fills up with fluid that interferes with the heart’s ability to pump blood.



Miliary tuberculosis. Miliary TB is a life-threatening
condition that occurs when large numbers of tubercle
bacilli spread throughout the body. Huge numbers of
tiny tubercular lesions develop that cause marked
weakness and weight loss, severe anemia, and gradual wasting of the body.
Diseases similar to tuberculosis

There are many forms of mycobacteria other than
M. tuberculosis, the tubercle bacillus. Some cause
infections that may closely resemble tuberculosis, but
they usually do so only when an infected person’s
immune system is defective. People who are HIV-positive are a prime example. The most common
3808

mycobacteria that infect AIDS patients are a group
known as Mycobacterium avium complex (MAC).
People infected by MAC are not contagious, but they
may develop a serious lung infection that is highly
resistant to antibiotics. MAC infections typically
start with the patient coughing up mucus. The infection progresses slowly, but eventually blood is brought
up and the patient has trouble breathing. In AIDS
patients, MAC disease can spread throughout the
body, with anemia, diarrhea, and stomach pain as
common features. Often these patients die unless
their immune system can be strengthened. Other
mycobacteria grow in swimming pools and may
cause skin infection. Some of them infect wounds and
artificial body parts such as a breast implant or
mechanical heart valve.

Diagnosis
The diagnosis of TB is made on the basis of
laboratory test results. The standard test for tuberculosis—which is the so-called tuberculin skin test—
detects the presence of infection, not of active TB.
Tuberculin is an extract prepared from cultures of
M. tuberculosis. It contains substances belonging to
the bacillus (antigens) to which an infected person has
been sensitized. When tuberculin is injected into the
skin of an infected person, the area around the injection becomes hard, swollen, and red within one to
three days. Today skin tests utilize a substance called
purified protein derivative (PPD) that has a standard
chemical composition and is therefore is a good measure of the presence of tubercular infection. The PPD
test is also called the Mantoux test. The Mantoux PPD
skin test is not, however, 100% accurate; it can produce false positive as well as false negative results.
What these terms mean is that some people who have
a skin reaction are not infected (false positive) and that
some who do not react are in fact infected (false negative). The PPD test is, however, useful as a screener.
Anyone who has suspicious findings on a chest x ray,
or any condition that makes TB more likely should
have a PPD test. In addition, those in close contact
with a TB patient and persons who come from a
country where TB is common also should be tested,
as should all healthcare personnel and those living in
crowded conditions or institutions.
Because the symptoms of TB cover a wide range
of severity and affected body parts, diagnosis on the
basis of external symptoms is not always possible.
Often, the first indication of TB is an abnormal chest
x-ray or other test result rather than physical discomfort. On a chest x ray, evidence of the disease appears
as numerous white, irregular areas against a dark
GALE ENCYCLOPEDIA OF MEDICINE

Body fluids other than sputum can be used for
culture. If TB has invaded the brain or spinal cord,
culturing a sample of spinal fluid will make the diagnosis. If TB of the kidneys is suspected because of pus
or blood in the urine, culture of the urine may reveal
tubercular infection. Infection of the ovaries in women
can be detected by placing a tube having a light on its
end (a laparoscope) into the area. Samples also may be
taken from the liver or bone marrow to detect the
tubercle bacillus.
One important new advance in the diagnosis of
TB is the use of molecular techniques to speed the
diagnostic process as well as improve its accuracy. As
of late 2005, four molecular techniques are increasingly used in laboratories around the world. They
include polymerase chain reaction to detect mycobacterial DNA in patient specimens; nucleic acid probes
to identify mycobacteria in culture; restriction fragment length polymorphism analysis to compare different strains of TB for epidemiological studies; and
genetic-based susceptibility testing to identify drugresistant strains of mycobacteria.

Treatment

Drug therapy
Most patients with TB can recover if given appropriate medication for a sufficient length of time. Three
principles govern modern drug treatment of TB:


Lowering the number of bacilli as quickly as possible.
This measure minimizes the risk of transmitting the
disease. When sputum cultures become negative, this
has been achieved. Conversely, if the sputum remains
positive afterfive to six months, treatment has failed.



Preventing the development of drug resistance. For
this reason, at least two different drugs and sometimes
three are always given at first. If drug resistance is
suspected, at least two different drugs should be tried.



Long-term treatment to prevent relapse.

Five drugs are most commonly used today to treat
tuberculosis: isoniazid (INH, Laniazid, Nydrazid); rifampin (Rifadin, Rimactane); pyrazinamide (Tebrazid);
streptomycin; and ethambutol (Myambutol). The first
three drugs may be given in the same capsule to minimize
the number of pills in the dosage. As of 1998, many
patients are given INH and rifampin together for six
months, with pyrazinamide added for the first two
months. Hospitalization is rarely necessary because
many patients are no longer infectious after about two
weeks of combination treatment. Follow-up involves
monitoring of side effects and monthly sputum tests.
Of the five medications, INH is the most frequently used
drug for both treatment and prevention.
Surgery
Surgical treatment of TB may be used if medications are ineffective. There are three surgical treatments for pulmonary TB: pneumothorax, in which
air is introduced into the chest to collapse the lung;
thoracoplasty, in which one or more ribs are removed;
and removal of a diseased lung, in whole or in part. It
is possible for patients to survive with one healthy
lung. Spinal TB may result in a severe deformity that
can be corrected surgically.

Supportive care
In the past, treatment of TB was primarily supportive. Patients were kept in isolation, encouraged to
rest, and fed well. If these measures failed the lung was
collapsed surgically so that it could ‘‘rest’’ and heal.
Today surgical procedures still are used when necessary, but contemporary medicine relies on drug therapy as the mainstay of home care. Given an effective
combination of drugs, patients with TB can be treated
at home as well as in a sanitorium. Treatment at home
does not pose the risk of infecting other household
members.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The prognosis for recovery from TB is good for
most patients, if the disease is diagnosed early and given
prompt treatment with appropriate medications on a
long-term regimen. According to a 2002 Johns Hopkins
study, most patients in the United States who die of
TB are older—average age 62— and suffer from such
underlying diseases as diabetes and kidney failure.
Modern surgical methods have a good outcome
in most cases in which they are needed. Miliary
3809

Tuberculosis

background, or as enlarged lymph nodes. The upper
parts of the lungs are most often affected. A PPD test
is always done to show whether the patient has been
infected by the tubercle bacillus. To verify the test
results, the physician obtains a sample of sputum or
a tissue sample (biopsy) for culture. Three to five
sputum samples should be taken early in the morning.
If necessary, sputum for culture can be produced by
spraying salt solution into the windpipe. Culturing
M. tuberculosis is useful for diagnosis because the
bacillus has certain distinctive characteristics. Unlike
many other types of bacteria, mycobacteria can retain
certain dyes even when exposed to acid. This so-called
acid-fast property is characteristic of the tubercle
bacillus.

Tuberculosis

KEY TERMS
Bacillus Calmette-Guérin (BCG)—A vaccine
made from a damaged bacillus akin to the tubercle
bacillus, which may help prevent serious pulmonary TB and its complications.
Mantoux test—Another name for the PPD test.
Miliary tuberculosis—The form of TB in which the
bacillus spreads through all body tissues and
organs, producing many thousands of tiny tubercular lesions. Miliary TB is often fatal unless promptly
treated.
Mycobacteria—A group of bacteria that includes
Mycobacterium tuberculosis, the bacterium that
causes tuberculosis, and other forms that cause
related illnesses.
Pneumothorax—Air inside the chest cavity, which
may cause the lung to collapse. Pneumothorax is
both a complication of pulmonary tuberculosis and
a means of treatment designed to allow an infected
lung to rest and heal.
Pulmonary—Referring to the lungs.
Purified protein derivative (PPD)—An extract of
tubercle bacilli that is injected into the skin to find
out whether a person presently has or has ever had
tuberculosis.
Resistance—A property of some bacteria that have
been exposed to a particular antibiotic and have
‘‘learned’’ how to survive in its presence.
Sputum—Secretions produced in the infected lung
and coughed up. A sign of illness, sputum is routinely used as a specimen for culturing the tubercle
bacillus in the laboratory.
Tuberculoma—A tumor-like mass in the brain that
sometimes develops as a complication of tuberculous meningitis.

tuberculosis is still fatal in many cases but is rarely
seen today in developed countries. Even in cases in
which the bacillus proves resistant to all of the commonly used medications for TB, other seldom-used
drugs may be tried because the tubercle bacilli have
not yet developed resistance to them.

aspects of prevention. Hospital emergency rooms and
similar locations can be treated with ultraviolet light,
which has an antibacterial effect.
Vaccination
Vaccination is one major preventive measure
against TB. A vaccine called BCG (Bacillus
Calmette-Guérin, named after its French developers)
is made from a weakened mycobacterium that infects
cattle. Vaccination with BCG does not prevent infection by M. tuberculosis but it does strengthen the
immune system of first-time TB patients. As a result,
serious complications are less likely to develop. BCG
is used more widely in developing countries than in the
United States. The effectiveness of vaccination is still
being studied; it is not clear whether the vaccine’s
effectiveness depends on the population in which it is
used or on variations in its formulation.
Prophylactic use of isoniazid
INH can be given for the prevention as well as the
treatment of TB. INH is effective when given daily
over a period of six to 12 months to people in highrisk categories. INH appears to be most beneficial to
persons under the age of 25. Because INH carries the
risk of side-effects (liver inflammation, nerve damage,
changes in mood and behavior), it is important to give
it only to persons at special risk.
High-risk groups for whom isoniazid prevention
may be justified include:


close contacts of TB patients, including health care
workers



newly infected patients whose skin test has turned
positive in the past two years



anyone who is HIV-positive with a positive PPD skin
test; Isoniazid may be given even if the PPD results
are negative if there is a risk of exposure to active
tuberculosis



intravenous drug users, even if they are negative for
HIV



persons with positive PPD results and evidence of old
disease on the chest x-ray who have never been treated for TB



patients who have an illness or are taking a drug that
can suppress the immune system



persons with positive PPD results who have had
intestinal surgery; have diabetes or chronic kidney
failure; have any type of cancer; or are more than
10% below their ideal body weight

Prevention
General measures
General measures such as avoidance of overcrowded and unsanitary conditions are also necessary
3810

GALE ENCYCLOPEDIA OF MEDICINE

people from countries with high rates of TB who
have positive PPD results



people from low-income groups with positive skin
test results



persons with a positive PPD reaction who belong
to high-risk ethnic groups (African Americans,
Hispanics, Native Americans, Asians, and Pacific
Islanders)

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Infectious Diseases Caused by Mycobacteria.’’
In The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Tuberculosis.’’ New York: Simon & Schuster, 2002.
PERIODICALS

‘‘Changing Patterns of New Tuberculosis Infections.’’
Infectious Disease Alert August 15, 2002: 171–172.
‘‘‘Drug of Dreams’ Preps for First Large-Scale Trail: Study
to Begin this Year; Moxifloxacin to Debut Soon in
Study 27.’’ TB Monitor July 2002: 73.
Efferen, Linda S. ‘‘Tuberculosis: Practical Solutions to Meet
the Challenge.’’ Journal of Respiratory Diseases
November 1999: 772.
Fielder, J. F., C. P. Chaulk, M. Dalvi, et al. ‘‘A High
Tuberculosis Case-Fatality Rate in a Setting of
Effective Tuberculosis Control: Implications for
Acceptable Treatment Success Rates.’’ International
Journal of Tuberculosis and Lung Disease 6 (December
2002): 1114–1117.
‘‘Guidelines Roll Out Two New Variations: Experts give
Both a Thumbs Up.’’ TB Monitor August 2002: 85.
Houston, H. R., N. Harada, and T. Makinodan.
‘‘Development of a Culturally Sensitive Educational
Intervention Program to Reduce the High Incidence of
Tuberculosis Among Foreign-Born Vietnamese.’’
Ethnic Health 7 (November 2002): 255–265.
Kim, D. Y., R. Ridzon, B. Giles, and T. Mireles. ‘‘PseudoOutbreak of Tuberculosis in Poultry Plant Workers,
Sussex County, Delaware.’’ Journal of Occupational
and Environmental Medicine 44 (December 2002): 1169–
1172.
Moua, M., F. A. Guerra, J. D. Moore, and R. O. Valdiserri.
‘‘Immigrant Health: Legal Tools/Legal Barriers.’’
Journal of Law and Medical Ethics 30, Supplement 3
(Fall 2002): 189–196.
‘‘New Drugs Sought for Top Killer of Young Women
Worldwide.’’ Women’s Health Weekly July 25, 2002: 20.
‘‘Poor Patient Compliance Key to Drug Resistance in
Tuberculosis.’’ Pulse July 1, 2002: 18.
GALE ENCYCLOPEDIA OF MEDICINE

Stauffer, W. M., D. Kamat, and P. F. Walker. ‘‘Screening of
International Immigrants, Refugees, and Adoptees.’’
Primary Care 29 (December 2002): 879–905.
Su, W. J. ‘‘Recent Advances in the Molecular Diagnosis of
Tuberculosis.’’ Journal of Microbiology, Immunology,
and Infection 35 (December 2002): 209–214.
ORGANIZATIONS

American Lung Association. 1740 Broadway, New York,
NY 10019. (800) 586-4872. <http://
www.lungusa.org>.
National Heart, Lung, and Blood Institute (NHLBI). P. O.
Box 30105, Bethesda, MD 20824-0105. (301) 592-8573.
<www.nhlbi.nih.gov>.
OTHER

New York State Department of Health. ‘‘Communicable
Disease Fact Sheet.’’

David A. Cramer, MD
Rebecca J. Frey, PhD

Tubo-ovarian abscesses see Pelvic inflammatory disease

Tularemia
Definition
Tularemia is an illness caused by a bacterium. It
results in fever, rash, and greatly enlarged lymph
nodes.

Description
Tularemia infects a variety of wild animals,
including rabbits, deer, squirrels, muskrat, and beaver. Humans can acquire the bacterium directly from
contact with the blood or body fluids of these animals,
from the bite of a tick or fly which has previously fed
on the blood of an infected animal, or from contaminated food or water.
Tularemia occurs most often in the summer
months. It is most likely to infect people who come
into contact with infected animals, including hunters,
furriers, butchers, laboratory workers, game wardens,
and veterinarians. In the United States, the vast
majority of cases of tularemia occur in the southeastern and Rocky Mountain states.

Causes and symptoms
Five types of illness may occur, depending on
where/how the bacteria enter the body:
3811

Tularemia



Tumor markers

Diagnosis

KEY TERMS
Conjunctiva—The lining of the eyelids and the surface of the white part of the eye.
Shock—A state in which drastically low blood
pressure prevents adequate blood flow to the tissues and organs throughout the body.







Ulceroglandular/glandular tularemia. Seventy-five to
85% of all cases are of this type. This type is contracted
through the bite of an infected tick that has defecated
bacteria-laden feces in the area of the bite wound.
A tender red bump appears in the area of the original
wound. Over a few weeks, the bump develops a
punched-out center (ulcer). Nearby lymph nodes grow
hugely swollen and very tender. The lymph nodes may
drain a thick, pus-like material. Other symptoms include
fever, chills, and weakness. In adults, the lymph nodes in
the groin are most commonly affected; in children, the
lymph nodes in the neck.
Oculoglandular tularemia. This type accounts for
only about 1% of all cases of tularemia. It occurs
when a person’s contaminated hand rubs his or her
eye. The lining of the eyelids and the surface of the
white of the eye (conjunctiva) becomes red and
severely painful, with multiple small yellow bumps
and pitted sores (ulcers). Lymph nodes around the
ears, under the jaw, or in the neck may swell and
become painful.
Oropharyngeal and gastrointestinal tularemia. This
type occurs when contaminated meat is undercooked
and then eaten, or when water from a contaminated
source is drunk. Poor hygiene after skinning and
cleaning an animal obtained through hunting can
also lead to the bacteria entering through the mouth.
Sores in the mouth and throat, as well as abdominal
pain, nausea and vomiting, ulcers in the intestine,
intestinal bleeding, and diarrhea may all occur.



Pulmonary tularemia. This rare type of tularemia
occurs when a person inhales a spray of infected
fluid, or when the bacteria reach the lungs through
the blood circulation. A severe pneumonia follows.



Typhoidal tularemia. This type of tularemia is particularly hard to diagnose, because it occurs without
the usual skin manifestations or swelling of lymph
glands. Symptoms include continuously high fever,
terrible headache, and confusion. The illness may
result in a severely low blood pressure, with signs of
poor blood flow to the major organs (shock).

3812

Samples from the skin lesions can be prepared
with special stains, to allow identification of the causative bacteria under the microscope. Other tests are
available to demonstrate the presence of antibodies
(special immune cells that the body produces in
response to the presence of specific foreign invaders)
which would be increasing over time in an infection
with tularemia.

Treatment
Streptomycin (given as a shot in a muscle) and
gentamicin (given as either a shot in a muscle or through
a needle in the vein) are both used to treat tularemia.
Other types of antibiotics have been tested, but have
often resulted in relatively high rates of relapse (20%).

Prognosis
With treatment, death rates from tularemia are
under 1%. Without treatment, however, the death
rate may reach 30%. The pneumonia and typhoidal
types have the worst prognosis without treatment.

Prevention
Prevention involves avoiding areas known to harbor ticks and flies, or the appropriate use of insect
repellents. Hunters should wear gloves when skinning
animals or preparing meat. Others (butchers, game
wardens, veterinarians) who work with animals or
carcasses should always wear gloves. A vaccine exists,
but is usually only given to people at very high risk due
to their profession or hobby (veterinarians, laboratory
workers, butchers, hunters, game wardens).
Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Tumor markers
Definition
Tumor markers are measurable biochemicals that
are associated with a malignancy. They are either
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
Though tumor markers are rarely specific enough
to be used alone to diagnose cancer, they do have a
number of clinical uses. They can be used to stage
cancer, to indicate a prognosis, to monitor treatment,
or in follow-up to watch for cancer recurrence.
Changes in some tumor markers have been sensitive
enough to be used as targets in clinical trials. When
used for diagnosis, tumor markers are used in conjunction with other clinical parameters such as biopsy
and radiological findings. Although there are a multitude of tumor markers, very few of them have found
their way into clinical practice because of their lack of
specificity. However, some of these non-specific markers have found a place in monitoring cancer treatment rather than in diagnosis.

Description
As tumor cells grow and multiply, some of their
substances can increase and leak into the bloodstream
or other fluids. Depending upon the tumor marker, it
can be measured in blood, urine, stool or tissue. Some
widely used tumor markers include: AFP, beta-HCG,
CA 15-3, CA 19-9, CA 27.29, CA 125, CEA, and PSA.
Some tumor markers are associated with many types
of cancer; others, with as few as one. Some tumor
markers are always elevated in specific cancers; most
are less predictable. However, no tumor marker is
specific for cancer and most are found in low levels
in healthy persons, or can be associated with nonneoplastic diseases as well as cancer. Also, no tumor
marker test is free of false negatives or false positives.
Once cancer is diagnosed, tumor marker levels
sometimes help to determine the extent of cancer.
Higher levels can indicate more advanced cancer and
a worse prognosis in some cases. The patient and their
physician may use this information to choose between
more or less aggressive treatments.
Monitoring cancer treatment is the most common
use of tumor markers. As cancer is reduced, levels
often decrease. Stable or increasing levels often indicate that the cancer is not responding to treatment.
GALE ENCYCLOPEDIA OF MEDICINE

The choice of tumor marker to use for monitoring is
important. Only a marker elevated before treatment
should be used to monitor a person during or after
treatment. Timing of the tests is also important. Each
tumor marker has a unique life span in the blood. To
monitor a treatment’s success, enough time must have
passed for the initial marker to be cleared from the
blood. Tests done too soon may be falsely elevated
because the marker produced by the untreated cancer
is still present.
Watching for cancer recurrence after treatment is
another reason for tumor marker testing. Periodic
testing can sometimes detect a recurrence often
months earlier than could an ultrasound, x ray, or
physical examination.
Tumor marker tests are performed in a lab using
immunological techniques. A sample of blood or other
tissue is mixed with a substance containing specific
antibodies to each tumor marker. If that tumor marker is present, these very specific antibodies bind to the
markers. Some type of label, often a radioactive substance, is then used to measure the amount of bound
marker and antibody. From this measurement, the
amount of tumor marker is calculated. The results
are usually available within a few days.
Conclusions based on tumor marker tests are seldom based on one test result but on a series of test
results, called serial measurements. A series of increasing or decreasing values is more significant than a
single value.
Tumor marker testing is currently the object of
much research and attention. Their use is directed by
approval from the Food and Drug Administration
(FDA) and guidelines established by organizations
such as the American Society of Clinical Oncology
and the American Cancer Society. Not all tumor
receptor marker tests are widely available nor are
they widely accepted.
Oncofetal antigens
There are two common oncofetal antigens, alphafetoprotein (AFP) and carcinoembryonic antigen
(CEA). Carcinoembryonic antigen CA 72-4 is a more
recently discovered oncofetal antigen just coming into
usage. The oncofetal antigens are so named because
they are normally produced during embryonic development and decrease soon after birth. Cancer cells
tend to dedifferentiate, or revert to a more immature
tissue and begin to produce fetal antigens again.
Oncofetal antigens are very non-specific and expressed
by a wide number of cancer types. However, they are
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Tumor markers

produced by tumor cells (tumor-derived) or by the
body in response to tumor cells (tumor-associated).
They are typically substances that are released into
the circulation and thus measured in the blood.
There are a few exceptions to this, such as tissuebound receptors that must be measured in a biopsy
from the solid tumor or proteins that are secreted into
the urine.

Tumor markers

used both to monitor a patient’s progress and their
response to treatment over time.
ALPHA-FETOPROTEIN (AFP). Elevated AFP typically indicates a primary liver tumor or a germ cell
tumor of the ovary or testicle. AFP is a glycoprotein
produced in high amounts by fetal tissue and is elevated during pregnancy. It is most widely used as a
marker for hepatocellular carcinoma and testicular
cancer but is also associated with ovarian cancer.
Seventy percent of people with liver cancer have
increased AFP levels. In China, where liver cancer
rates are high, AFP is used as a screening test for
that disease. AFP levels indicate the extent of cancer,
and serial measurements are used to monitor treatment response. Non-cancerous liver conditions such
as cirrhosis and hepatitis have moderately increased
levels of AFP.
CARCINOEMBRYONIC ANTIGEN (CEA). CEA is a
glycoprotein most often associated with colorectal
cancer, and used to monitor patients with this type of
cancer. Its most popular use is in early detection of
relapse in individuals already treated for colorectal
cancer. After surgery, serial measurements indicate
the surgery’s success and are used to detect early
signs of recurrence. It has recently been found to be
useful when measured during surgery for colorectal
cancer to help determine prognosis and who will benefit from adjuvant treatment.

CEA is measured in the blood plasma. It is very
non-specific and can be increased in many types of
cancer: gastrointestinal, colorectal, ovarian, bladder,
cervical, stomach, kidney, lung, pancreatic, liver, prostate, thyroid, melanoma, lymphoma, and breast.
People with noncancerous conditions, such as cirrhosis or peptic disease, or inflammatory intestinal conditions such as colitis or diverticulitis, may also have
increased levels. CEA levels can be elevated in elderly
patients and in those who smoke.
CANCER ANTIGEN 72-4 (CA 72-4). The more recently
identified carcinoembryonic protein is CA 72-4.
Although it is slightly elevated with most carcinomas,
it is mostly associated with gastric carcinoma (stomach
cancer). CA 74-2 is finding a role in the management of
patients with gastric carcinoma.

Cancer antigen 15-3 (CA 15-3)
CA 15-3 is produced by cells in the breast and
increased levels can be associated with breast cancer.
Rarely increased in women with early breast cancer, it
may be used to detect recurrence of cancer in women
following treatment or mastectomy and to monitor
treatment for women with advanced breast cancer.
3814

However, adenocarcinomas of the ovary, lung,
colon, and pancreas also express elevated CA 15-3
levels. Non-cancerous conditions sometimes associated with elevated CA 15-3 include benign breast or
ovarian disease, endometriosis, pelvic inflammatory
disease, and hepatitis. Pregnancy and lactation are
also related to high CA 15-3 levels.
Cancer antigen 27-29 (CA 27-29)
CA 27-29, also called breast carcinoma-associated
antigen, is used as a marker for breast cancer. Eighty
percent of women with breast cancer have an
increased CA 27-29 level. This marker may be used
with other procedures and tumor marker levels such as
CA 15-3 to check for recurrences of cancer in previously treated women. Serial measurements monitor
treatment response and identify recurrence.
Levels of CA 27-29 may also be increased in cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver. Noncancerous conditions
associated with elevated CA 27-29 include first trimester pregnancy, endometriosis, ovarian cysts, non-cancerous breast disease, kidney disease, and liver disease.
HER-2/neu
HER-2/neu is an oncogenic growth factor receptor also known as c-erbB-2. It is measured in the tissue
from a biopsy either by immunological assays of the
protein or polymerase chain reaction (PCR) to identify the DNA. The presence of HER-2/neu is generally
associated with a poorer prognosis for breast cancer.
It can also help to determine treatment options, since
newer drugs can block this protein and decrease cancer
growth. The most widely known of these drugs is
trastuzumab (brand name Herceptin).
Estrogen receptor
Measurement of the estrogen receptor (ER)is used
specifically to evaluate breast cancers. It gives an indication of prognosis and responsiveness to therapy.
Tissue from a biopsy is used to measure the estrogen
receptor. Most breast cancers in post-menopausal
women are ER-positive, meaning that they require
estrogen to grow. These ER positive breast cancers
are less aggressive than ER negative breast cancers,
which are found generally in pre-menopausal women.
Cancer antigen 125 (CA 125)
Although produced by a number of cell types, CA
125 is primarily produced by ovarian cancer cells.
Eighty percent of women with ovarian cancer have
GALE ENCYCLOPEDIA OF MEDICINE

Women may have increased CA 125 levels during
menstruation and pregnancy. Increased levels are also
found in pelvic inflammatory disease, endometriosis,
pancreatitis, and liver disease. Elevated levels are also
associated with non-ovarian cancers including cancers
of the uterus, cervix, pancreas, liver, colon, breast,
lung, or digestive tract.
Prostate specific antigen (PSA)
Prostate specific antigen (PSA) levels, along with
the digital rectal examination, are used to screen for
prostate cancer. PSA is a protein produced by the
prostate gland and can be overproduced in prostate
cancer. It is perhaps the best tumor marker in use
because of its tissue specificity, meaning that it is
produced only by the prostate. Men over the age of
50 years are advised to consider annual screening for
prostate cancer. Men at high risk for prostate cancer,
such as African Americans or those with a family
history of the disease, should begin screening at age
40. Once a diagnosis of prostate cancer is made, PSA
levels can help determine the stage of the cancer,
monitor the response to treatment, and watch for
recurrence.
Measurements of PSA following prostatectomy
are useful in determining the success of surgery. Any
PSA level following surgery would indicate residual
prostate tissue, possibly from metastasis. PSA levels
can also be used to detect a recurrence of prostate
cancer. PSA is also increased in benign prostatic
hyperplasia (BPH), an enlarged prostate condition
common in older men.
PSA can be found in the serum in two states,
bound and free. Measuring both PSA levels can provide more specificity to the test and reduce unnecessary biopsies. The percentage of free PSA is greater in
BPH than prostate cancer. If the total PSA level is
higher than 4.0 nanogram/milliliter (ng/mL) and the
free PSA level is less than 25%, a prostate biopsy is
indicated.
GALE ENCYCLOPEDIA OF MEDICINE

PSA levels may increase after ejaculation. Men are
recommended to abstain from sexual intercourse or
masturbation for 48 hours before the test. PSA levels
may also increase after prostate manipulation following the digital rectal exam.
Prostatic acid phosphatase (PAP) originally found
to be produced by the prostate and thought to be a
marker for prostate cancer. It is now found to be elevated with testicular cancer, leukemia, non-Hodgkin’s
lymphoma and several noncancerous conditions.
Cancer antigen 19-9 (CA 19-9)
CA 19-9 has been identified in patients with digestive tract or intra-abdominal carcinomas such as colorectal cancer, pancreatic cancer, stomach cancer and bile
duct cancer. In pancreatic cancer, higher levels are associated with more advanced disease. After diagnosis,
levels help predict the success of surgery and monitor
the course of the cancer. Not all people with pancreatic
cancer have increased CA 19-9 levels. This antigen is
related to the Lewis blood group and so only patients
positive for the Lewis blood group antigen will test
positive for CA 19-9. It is also increased in liver and
gastrointestinal cancers and in noncancerous diseases,
including pancreatitis, gallstones and jaundice.
Human chorionic gonadotropin (hCG)
Human chorionic gonadotropin is normally produced by the placenta during pregnancy. There are
two protein subunits that make up HCG, beta and
alpha. It is the beta subunit that is increased in
women’s serum during early pregnancy. It is also the
beta subunit that is increased in some malignant
tumors. Tumors that secrete beta-hCG are typically
germ cell tumors such as teratocarcinomas. These are
tumors found in the ovaries and testes that contain
embryonal tissue. Rarely, these types of tumors are
found in the pineal region of the brain where betahCG can serve as a marker. Levels of hCG rise with
choriocarcinoma and with trophoblastic disease, a rare
cancer that develops from an abnormally fertilized
egg. Gestational trophoblastic tumors also secrete
AFP and this test is often used in combination.
HCG is most often used to screen for cancer of the
testis or ovary. Serial measurements monitor the progress and treatment of these cancers. This marker can
be elevated in individuals who use marijuana.
Squamous cell carcinoma (SCC) Antigen
Squamous cell carcinoma (SCC) antigen was first
identified in cervical cancer. It is a marker for squamous cell cancers, which can occur in the cervix, head
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Tumor markers

increased CA 125 levels. Although the test is not sensitive or specific enough to be used for screening, it
contributes to a diagnosis when combined with an
ultrasound and pelvic examination. Blood levels of
CA 125 are used primarily to monitor the treatment
of ovarian cancer. A falling CA 125 level usually indicates that cancer is responding to the treatment. After
diagnosis and treatment, serial measurements help
detect remaining or recurrent cancer. A negative or
normal result, however, does not guarantee the
absence of cancer.

Tumor markers

and neck, lung, and skin. Levels of SCC can be used as
an aid to stage the carcinoma and to determine the
response to treatment.
Bence-Jones protein
Patients with plasmacytomas such as myeloma
overproduce monoclonal immunoglobulins, also
called M proteins. The Bence-Jones protein refers to
the immunoglobulin light chain, a portion of these
immunoglobulins. The Bence-Jones protein is secreted
into the urine where it can be measured. It was the first
tumor marker identified.
Neuron-specific enolase (NSE)
NSE is a protein found mainly in neurons and
neuroendocrine cells. It is elevated in tumors derived
from these tissues, including neuroblastoma and small
cell lung cancer. It can give information about the
extent of the disease, the patient’s prognosis and the
patient’s response to treatment. NSE can also be elevated in medullary thyroid cancers, carcinoid tumors,
pancreatic endocrine tumors, and melanoma.
Hormone assays
Tumors of the endocrine glands oversecrete their
corresponding hormones. By measuring particular
hormones, clues can be obtained regarding certain
cancers. For instance, breast cancer cells may secrete
prolactin and estrogen. Medullary carcinoma can
secrete calcitonin. Pheochromocytomas secrete catecholamines. Tumors of the pituitary gland may secrete
growth hormone or cortisol. Carcinoid tumors secrete
serotonin. Some tumors of the pancreas secrete insulin. Serial measurements can also monitor treatment
for these tumors.
Enzymes
Several serum enzymes can be measured to help
detect metastases in cancer patients. Tumors that
metastasize to the liver cause increases in serum alkaline phosphatase, gamma-glutamyltransferase, and
transaminases. Although these are not necessarily
tumor markers, they indicate liver damage that may
be caused by metastatic cancer. Tumors that metastasize to the bone sometimes secrete elevated alkaline
phosphatase. Lactate dehydrogenase is an enzyme
found throughout the body. Because of this it cannot
be used as a marker for cancer. It can, however, be
used to monitor the treatment of some types of cancer
including germ cell tumors, testicular cancer, Ewing’s
sarcoma, non-Hodgkins lymphoma and some types of
leukemia.
3816

Precautions
There is not a good consensus in the medical
community about the value of most tumor markers.
Because they lack specificity and accuracy, their use is
limited. False positives can cause emotional distress
and fear. It is not yet determined if there is a savings of
life or money with testing. Currently, much controversy surrounds the issue of mass screening for cancer
using tumor markers.

Preparation
Tumor marker tests usually require 5-10 mL of
blood. A healthcare worker ties a tourniquet on the
patient’s upper arm, locates a vein in the inner elbow
region, and inserts a needle into that vein. Vacuum
action draws the blood through the needle into an
attached tube. Collection of the sample takes a few
minutes and results are available within a few days.
Some markers, such as those for bladder cancer,
multiple myeloma, and plasmacytomas, are measured
in the urine. Typically this requires a 24-hour urine
sample, which means that the individual must collect
all of his or her urine for 24 hours. This is usually
about 1.5 quarts or more. These results are then available within a few days.
Other tumor markers require tissue samples for
analysis. These include receptor analysis such as estrogen receptor and Her-2/neu. Tissue samples are
obtained by biopsy. This is usually done by inserting
a needle through the skin and into the tumor. The area
is typically numbed prior to the procedure. These
results are also available within two to three days.

Aftercare
Discomfort or bruising may occur at the puncture
site or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve discomfort. There is a rare chance of infection occurring
especially after biopsy. Any sign of infections should
be watched for such as pain and redness.

Normal results


AFP: 99% of (nonpregnant) people have less than 15
ng/mL; 95% have less than 6 ng/mL. Serum AFP
levels higher than 400 micrograms/L are associated
with cancer or some other pathology.



Beta-HCG: in males, less than 2.5 IU/L; in females,
less than 5.0 IU/L; in postmenopausal females, less
than 9.0 IU/L.
GALE ENCYCLOPEDIA OF MEDICINE

AFP (Alpha-fetoprotein)—A tumor marker associated with liver, testicular, and ovarian cancer.
Beta-HCG (Beta-human chorionic gonadotropin)—A tumor marker associated with testicular
cancer and tumors, such as choriocarcinoma and
molar pregnancies, that begin in placental cells
called trophoblasts.
Biopsy—The process of taking a sample of tumor
tissue through a needle.
CA 15-3 (Cancer antigen 15-3)—A tumor marker
associated with breast cancer.
CA 19-9 (Cancer antigen 19-9)—A tumor marker
associated with pancreatic cancer.
CA 27-29 (Breast carcinoma-associated antigen)—A tumor marker associated with breast
cancer.
CA 125 (Cancer antigen 125)—A tumor marker
associated with ovarian cancer.
CEA (Carcinoembryonic antigen)—A tumor marker associated with many cancers, especially liver,
intestinal, and pancreatic.
Prognosis—The predicted outcome of a disease.
PSA (Prostate specific antigen)—A tumor marker
associated with prostate cancer.
Sensitivity—A test’s ability to detect all cases of a
disease.
Serial measurements—A series of measurements
looking for an increase or decrease over time.
Specificity—A test’s ability to detect only the disease in question.
Tumor markers—Biochemicals produced by
tumor cells or by the body in response to tumor
cells. Their levels in the blood help evaluate people
for certain kinds of cancer.



CA 15-3: less than 40 U/mL.



CA 19-9: less than 40 U/mL.



CA 27.29: less than or equal to 38 U/mL.



CA 125: less than 35 U/L.



CEA: less than or equal to 5 ng/mL.



PSA: less than 4 ng/mL; PSA levels increase with age.
Age-specific values range from 2.0 micrograms/L at
age 40 to 7.2 micrograms/L at age 80. Typically, levels
below 4.0 micrograms/L rule out prostate cancer.

GALE ENCYCLOPEDIA OF MEDICINE

The meaning of an increased tumor marker level
depends on the specific marker, the person’s medical
history, and why the test was done. Knowledge of the
patient’s history and additional tests and physical
examinations are needed to correctly interpret tumor
marker test results.
Resources
BOOKS

Eissa, S. Tumor Markers. Philadelphia: Lippincott Williams
& Wilkins, 1999.
Henry, John B. Clinical Diagnosis and Management by
Laboratory Methods. 20th ed. Philadelphia: W. B.
Saunders Company, 2001.
PERIODICALS

Bast, R. C., P. Ravdin, D. F. Hayes, et al. ‘‘2000 Update
Recommendations for the Use of Tumor Markers in
Breast and Colorectal Cancer.’’ Journal of Clinical
Oncology 19, no. 6 (2001).
Daugaard, G. ‘‘The Clinical Use of Tumor Markers in Germ
Cell Cancer.’’ Journal of Tumor Marker Oncology 16,
no. 1 (2001).
Eriksson, B., K. Oberg, and M. Stridsberg. ‘‘Tumor Markers
in Neuroendocrine Tumors.’’ Digestion 62, no. 1 (2000).
Lindblom, Annika, and Annelie Liljegren. ‘‘Tumor Markers
in Malignancies.’’ British Medical Journal 320 (2000):
424.
Ruckdeschel, John C. ‘‘Update in Oncology.’’ Annals of
Internal Medicine 131 (1999): 760–7.
Salgia, R., D. Harpole, J. E. Herndon, and others. ‘‘Role of
Serum Tumor Markers CA125 and CEA in Non-small
Cell Lung Cancer.’’ Anticancer Research 21, no. 2
(2001).
ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta,
GA 30329-4251. (800) 227-2345. <http://
www.cancer.org>.
American Society of Clinical Oncology. 225 Reinekers Lane,
Suite 650, Alexandria, VA 22314. (703) 299-0150.
<http://www.asco.org>.
National Cancer Institute. Building 31, Room 10A31, 31
Center Drive, MSC 2580, Bethesda, MD 20892-2580.
(800) 422-6237. <http://www.nci.nih.gov>.
OTHER

National Cancer Institute. ‘‘NCI Fact Sheet: Tumor
Markers.’’ April 1998. [cited July 17, 2001]. <http://
www.oncolink.upenn.edu/pdq_html/6/engl/
600518.html>.
National Cancer Institute. ‘‘Screening for Ovarian Cancer.’’
May 1998. June 11, 1998. [cited July 17,2001]. <http://
cancernet.nci.nih.gov/clinpdq/screening/
Screening_for_ovarian_cancer_Physician.html>.
National Cancer Institute. ‘‘Screening for Prostate Cancer.’’
May 1998. June 11, 1998. [cited July 17, 2001]. <http://
3817

Tumor markers

Abnormal results

KEY TERMS

Tumor removal

cancernet.nci.nih.gov/clinpdq/screening/
Screening_for_prostate_cancer_Physician.html>.

Nancy J. Nordenson

Tumor removal
Definition
Tumor removal is a surgical procedure to remove
an abnormal growth.

Purpose
A tumor can be either benign, like a wart, or
malignant, in which case it is a cancer. Benign tumors
are well circumscribed and generally are easy to
remove completely. In contrast, cancers pose some of
the most difficult problems in all of surgery.
Currently 40% of all cancers are treated with
surgery alone. In 55% of cases, surgery is combined
with other treatments — usually radiation therapy or
chemotherapy.
The doctor needs to decide if surgery should be
done at all. Because cancers spread (metastasize) to
normal tissues, sometimes at the other end of the
body, the ability of surgery to cure must be addressed
at the outset. As long as the cancer is localized, the
initial presumption is that cure should be attempted by
removing it as soon as possible.
Non-curative surgery may make other treatments
more effective. ‘‘Debulking’’ a cancer–making it smaller–is thought to assist radiation and chemotherapy to
get to the remaining pieces of the cancer and be more
effective. Physicians apply standards and guidelines
based on research to the specific situation of a given
patient s situation to decide the best approach. For
example, reports released in 2003 said a study of
patients with a common form of brain tumor called
glioma had a more favorable outcome if their tumors
were removed than if a biopsy were just performed.
Another important function surgery performs in
cancer treatment is accurately assessing the nature and
extent of the cancer. Most cancers cannot be adequately identified without a piece being placed under
a microscope. This piece is obtained by surgery.
Surgery also is the only way to determine exactly
how far the tumor has spread. There are a few standard methods of comparing one cancer to another for
the purposes of comparing treatments and estimating
3818

A tumor inside the brain is being removed. (Photograph by
Jennifer Watson-Holton, Custom Medical Stock Photo.
Reproduced by permission.)

outcomes. These methods are called ‘‘staging.’’ The
most universal method is the TNM system.


‘‘T’’ stands for ‘‘tumor’’ and reflects the size of the
tumor.



‘‘N’’ represents the spread of the cancer to lymph
nodes, largely determined by those nodes removed
at surgery that contain cancer cells. Since cancers
spread mostly through the lymph system and this is
a useful measure of their ability to disperse.



‘‘M’’ refers to the metastases, how far they are from
the original cancer and how often they have
multiplied.

Other methods of staging include Duke’s method
and similar systems, which add the degree of invasion
of the cancer into the surrounding tissues to the above
criteria.
Staging is particularly important with such lymphomas as Hodgkin’s disease. These cancers may
appear in many places in the lymphatic system.
Because they are very radiosensitive, radiation treatment often is curative if all the cancer is irradiated.
Therefore, it must all be located. Surgery is a common,
usually essential, method of performing this staging. If
the disease is too widespread, the staging procedure
will dictate chemotherapy instead of radiation.

Precautions
Curative cancer surgery demands special considerations. There is a danger of spreading or seeding the
cancer during the process of removing it. Presuming the
cancer cells can grow almost anywhere in the body to
which they spread, the surgeon must not ‘‘spill’’ cells
into the operating field or ‘‘knock them loose’’ into the
blood stream. Special techniques called ‘‘block
GALE ENCYCLOPEDIA OF MEDICINE

sick individuals in the hospital, his son Judah dreamed of
becoming a surgeon. Young Folkman requested a microscope for his bah mitzvah present and upon receiving it, set
up a laboratory in his parents basement.
Folkman entered Ohio State University as a pre-med
student, graduating in 1953 after only three years of study.
He then went on to Harvard Medical School, where he
helped create one of the first pacemakers ever produced
and he received his medical degree in 1957. Folkman
completed his internship and residency at Massachusetts
General Hospital in Boston. In 1960, he married Paula
Prial and the couple moved to Bethesda, Maryland where
Folkman worked as a lieutenant in the U.S. Navy at the
National Naval Medical Center. It was here, with the help
of his colleague, Fredrich Becker, that Folkman would
make his initial discovery dealing with angiogenesis.
Folkman found that a tumor would only grow if it had
blood supplied to it. Additionally, the tumor would promote the growth of new blood vessels.
(AP Wide World Photos. Reproduced by permission.)

Moses Judah Folkman was born in Cleveland, Ohio,
on February 24, 1933. He was one of three children born to
Bessie and Jerome Folkman. Because Folkman s father, a
rabbi, would take his children with him when he visited

resection’’ and ‘‘no touch’’ are used. Block resection
means taking the entire specimen out as a single piece.
‘‘No touch’’ means that only the normal tissue removed
with specimen is handled; the cancer itself is never
touched. This prevents ‘‘squeezing’’ cancer cells out
into the circulation. Further, in this technique pains
are taken to clamp off the blood supply first, preventing
cells from leaving by that route later in the surgery.

Description
Diagnostic biopsies
There are four types of biopsy techniques. The
physician will choose the appropriate technique
depending on the tumor type, location, size, and
other factors. Some types of biopsy are more invasive
than others.




Aspiration biopsy. A needle is inserted into the
tumor and a sample is withdrawn.
Needle biopsy. A special cutting needle is inserted
into the core of the tumor and a core sample is
cut out.

GALE ENCYCLOPEDIA OF MEDICINE

Folkman also held positions as a professor and surgeon for many years, but in 1981, he retired and became
director of the Children’s Hospital Surgical Research
Laboratories in Boston. Folkman s research has opened
new doorways that may allow scientists to ultimately find
a cure for cancer.



Incisional biopsy. A portion of a large tumor is
removed, usually before complete tumor removal.



Excisional biopsy. A whole lesion is removed along
with surrounding normal tissue.
Complete tumor removal

Once surgical removal has been decided, an oncologic surgeon will remove the tumor whole, taking
with it a large section of the surrounding normal tissue. The healthy tissue is removed to minimize the risk
of possible seeding.
Cytoreduction
When surgical removal of a tumor is unacceptable
as a sole treatment, a portion of the tumor is removed
to ‘‘debulk’’ the mass. Debulking aids radiation and
chemotherapy treatments.

Aftercare
Retesting and periodical examinations are necessary to ensure that a tumor has not reformed after
total removal.
3819

Tumor removal

M O S E S J U D A H F O L K M A N (1933– )

Tumor removal

Benign tumors are generally
self-contained and localized
and have a well-defined
perimeter.

They are dangerous when they
compress surrounding tissues.
A benign tumor near a blood
vessel could restrict the flow of
blood; in the abdomen it could
impair digestion; in the brain it
could cause paralysis.

They grow slowly,
expanding outward
from a central mass.

Malignant tumors are
not self-contained, and
usually do not compress
surrounding tissues. Their
growth is an irregular
invasion of adjacent cells.
Although they may
grow slowly, they are
also capable of very
rapid growth.

They are not localized; in
a process called metastasis
they shed cells that travel
through the bloodstream
and infect tissues at other
locations. They can even
establish malignant growth
in a different type of tissue;
a breast cancer can spread
to bone tissue, for example.

A comparison of benign (top of illustration) and malignant tumor characteristics. (Illustration by Hans & Cassady, Inc.)

Risks
The possibility of mestastasis and seeding are
risks that have to be considered in consultation
with an oncologist. The advancement in imaging
techniques has led to some tumor staging by techniques like positron emission tomography (PET)
scanning. A needle biopsy may still be required to
confirm a diagnosis or staging decision, but in
some cases, imaging can replace an initial need
for biopsy.
3820

Resources
PERIODICALS

‘‘PET Scan, Endcoscopic Ulrsound Show Promise in
Staging for Lung Cancer Surgery.’’Biotech Week July 9,
2003: 181.
‘‘Study of Brain Tumors Points to Resection Over Biopsy
as One Key to Survival.’’Cancer Weekly October 28,
2003: 20.

J. Ricker Polsdorfer, MD
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Turner syndrome is a chromosomal disorder
affecting females wherein one of the two X-chromosomes is defective or completely absent.

Description
Chromosomes are structures in the nucleus of
every cell in the human body. Chromosomes contain
the genetic information necessary to direct the growth
and normal functioning of all cells and systems of the
body. A normal individual has a total of 46 chromosomes in each cell, two of which are responsible for
determining gender. Normally, females have two
X-chromosomes and males have one X and one
Y-chromosome.
In Turner syndrome, an error occurring very early
in development results in an abnormal number and
arrangement of chromosomes. Most commonly, an
individual with Turner syndrome will be born with
45 chromosomes in each cell rather than 46. The missing chromosome is an X-chromosome. The affected
person is always female.
The prevalence of Turner syndrome is widely
reported as being approximately one per 2,000 live
female births, although researchers have reported prevalence rates that range from one in 3,125 to one in
5,000 live female births.
About 1% to 2% of all female conceptions have a
missing X-chromosome. Of these, the majority (99%)
spontaneously abort, usually during the first trimester
of pregnancy. With ultrasound being used more frequently, researchers have realized that some pregnancies with a missing X-chromosome that progress into
the second trimester are associated with nuchal cysts,
severe lymphedema, or hydrops fetalis. These pregnancies are associated with a high frequency of fetal death.

Causes and symptoms
Turner’s syndrome is a disorder associated with
characteristic defects in the X-chromosome. The most
common presentation is a female with a single
X-chromosome and an absent X-chromosome. A
Greek study from 1999 reported that the intact
X-chromosome was as likely to come from the mother
as from the father. This means that there is no parental
pattern of responsibility for the missing or defective
X-chromosome.
GALE ENCYCLOPEDIA OF MEDICINE

The exact location of the genes on the X-chromosome involved in Turner syndrome has not been determined as of 2001. At present, evidence exists that there
is a locus for stature on the distal portion of the short
arm; there are loci for normal ovarian function on
both the short and long arms; and there are loci contributing to fetal viability on the long arm of X.
Turner syndrome is characterized by retarded
growth that leads to a small stature and frequent
infertility. Individuals with Turner syndrome report
an increased incidence of fractures in childhood and
osteoporotic fractures in adulthood. The incidence of
diabetes mellitus (both insulin dependent and noninsulin dependent varieties) has been reported to be
increased in Turner syndrome. Ischemic heart disease,
stroke and hypertension are also more common.
Growth in children with Turner syndrome is characterized by a slight intrauterine growth retardation,
relatively normal growth rates for the first several
years of life, a progressive deceleration of growth
later in childhood, and the lack of a pubertal growth
spurt. Growth patterns of Chinese girls with Turner
syndrome parallel those of Caucasians, although their
ultimate height is still less than normal.
Contrary to earlier reports, most individuals with
Turner syndrome are not mentally retarded. They may
have some learning disabilities, particularly with regard
to spatial perception, visual-motor coordination, and
mathematics. As a result, the nonverbal IQ in Turner
syndrome tends to be lower than the verbal IQ.
Cardiovascular malformations are well-recognized
congenital anomalies in Turner syndrome. Dilation and
dissection of the aorta are reported in approximately
half of women with Turner syndrome. Because of the
potential consequences of aortic dilation, some experts
recommend screening all individuals with Turner syndrome. However, the specific timing for this screening
remains controversial in 2001.
Juvenile arthritis, an autoimmune condition, has
been recently (1998) associated with Turner syndrome.
The prevalence seems to be at least six times greater than
would be expected if the two conditions were only randomly associated. Women with Turner syndrome have
an elevated prevalence rate of dental caries and such
other periodontal conditions as gum disease and plaque.
3821

Turner syndrome

Turner syndrome

Another less common genetic pattern for Turner
Syndrome (35%) is a mosaic. A Danish study reported
that mosaicism has an effect on malformations that
are associated with Turner syndrome. Research
reported in 1997 noted that the karyotype can have a
significant effect on the growth of children with
Turner syndrome.

Turner syndrome

KEY TERMS
Chromosome—A microscopic thread-like structure
found within each cell of the body that consists of a
complex of proteins and DNA. Humans have 46
chromosomes arranged into 23 pairs. Changes in
either the total number of chromosomes or their
shape and size (structure) may lead to physical or
mental abnormalities.
Mosaic—A term referring to a genetic situation in
which an individual’s cells do not have the exact
same composition of chromosomes. In Down syndrome, this may mean that some of the individual’s
cells have a normal 46 chromosomes, while other
cells have an abnormal 47 chromosomes.
Ovary—The female reproductive organ that produces the reproductive cell (ovum) and female
hormones.
A low hairline at the back of the neck is one of several characteristics of Turner syndrome. (Custom Medical Stock Photo.
Reproduced by permission.)

Normal pubertal development and spontaneous
menstrual periods do not occur in the majority of
children with Turner’ syndrome. It is estimated that
3–8% of girls with a single X-chromosome and 12–
21% of females with sex chromosome mosaicism may
have normal pubertal development and spontaneous
menstrual periods. A few pregnancies have been
reported in women with Turner syndrome.

Zygote—The cell formed by the uniting of egg and
sperm.

Experts recommend that therapy begin when a woman
expresses concern about her onset of puberty.
All women receiving long-term, exogenous female
hormone therapy require periodic gynecological
examinations, because those with Turner syndrome
have an increased risk of developing neoplasms such
as gonadoblastoma and dysgerminoma, which arise
from their rudimentary streak gonads.

Diagnosis
Turner syndrome is diagnosed on the basis of
genetic analysis of chromosomes. This can be done
prior to birth. However, the predictive value of amniocentesis in diagnosing Turner syndrome varies from
21–67%. There is no significant relation between the
mother’s age and risk of Turner’s syndrome.

Treatment
Because it is so dangerous, experts suggest screening for aortic dissection, although the specific timing
for this screening is controversial. Plastic surgery to
correct webbing of the neck should be considered at an
early age (before entering school) for girls with Turner
syndrome.
Most individuals with Turner syndrome require
female hormone therapy to promote development of
secondary sexual characteristics and menstruation.
The time of beginning therapy varies with individuals.
3822

Prognosis
Most women with Turner syndrome can live relatively normal lives. The prognosis for a person with
Turner syndrome is dependent on other conditions
that may be present. Care must be taken to regularly
monitor them for the health problems that are associated with Turner syndrome. For example, heart or
kidney defects, hearing loss, or the development of
inflammatory bowel disease may significantly impact
the quality of life. Without these types of conditions,
however, their life expectancy is normal. Support will
be necessary to help an adolescent girl cope with body
image issues and to help some women accept the fact
that they will never be able to have children.
Resources
BOOKS

Hall, Judith G. ‘‘Chromosomal Clinical Abnormalities.’’ In
Nelson Textbook of Pediatrics, edited by Richard E
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Academy of Pediatrics. 141 Northwest Point
Blvd., Elk Grove Village, IL 60007-1098. (847) 4344000. Fax: (847) 434-8000. <http://www.aap.org/visit/
contact.htm>.
Endocrine Society. 4350 East West Highway, Suite 500,
Bethesda, MD 20814-4410. (301) 941-0200. Fax: (301)
941-0259. endostaff@endo-society.org.
Human Growth Foundation. 997 Glen Cove Ave., Glen
Head, NY 11545. (800) 451-6434. Fax: (516) 671-4055.
<http://www.hgfound.org>.
Turner Syndrome Society of Canada. 7777 Keele St, Floor 2,
Concord, ONT L4K 1Y7. Canada (800) 465-6744 or
(416) 660-7766. Fax: (416) 660-7450.
Turner Syndrome Society of England. 2 Mayfield Ave.,
London, W41PW. UK 44 (0)181-994 7625. Fax: 44
(0)181-995 9075. <http://www.exnet.com/staff/sys4/
ts.html> or <http://www.tss.org.uk>.
OTHER

American Academy of Pediatrics. <http://www.aap.org/
visit/contact.htm>.
On-ramp Access. <http://www.onr.com/ts-texas/
turner.html>.
Turner Syndrome Support Society(UK). <http://
www.tss.org.uk/>.
University of Kansas Medical Center. <http://www
.kumc.edu/gec/support/turner.html>.

L. Fleming Fallon, MD, PhD, DrPH

Twins see Multiple pregnancy

Increasing the amount of 2,3-DPG is the body’s
primary way of responding to a lack of oxygen.
Anemia, obstructive lung disease, cystic fibrosis, and
congenital heart disease are all accompanied by
increases in 2,3-DPG. When more oxygen is required
because of increased metabolism, such as in hyperthyroidism, more 2,3-DPG is produced.
Decreased 2,3-DPG results from an inherited lack
of the red blood cell enzymes 2,3-DPG mutase and
2,3-DPG phosphatase. These enzymes are needed to
make 2,3-DPG. Without 2,3-DPG to control the
movement of oxygen to its tissues, the body responds
by making more red blood cells, a condition called
erythrocytosis. The outside membrane of the cell is
weakened, causing it to have an irregular shape and
burst, or hemolyze, easily. This condition is called
nonspherocytic hemolytic anemia.
2,3-DPG levels are important in large blood transfusions, because stored blood quickly loses 2,3-DPG
and its ability to deliver oxygen. After transfusion, the
red cells rebuild the 2,3-DPG, but it takes about 24
hours to regain a normal level of 2,3-DPG and hemoglobin function.

Description
In the laboratory, a person’s serum is mixed with a
substance that will react with 2,3-DPG. The end product of this reaction is measured; and from that measurement, the amount of 2,3-DPG in the person’s
serum is determined. Results are usually available the
next day.

Preparation

2,3-diphosphoglycerate test
Definition
2,3-diphosphoglycerate (2,3-DPG) is a substance
made in the red blood cells. It controls the movement
of oxygen from red blood cells to body tissues. 2,3DPG testing is done to help investigate both a deficiency in red blood cells (anemia) and an unexplained
increase of red blood cells, called erythrocytosis.

Purpose
Hemoglobin, the protein in the blood that carries
oxygen, uses 2,3-DPG to control how much oxygen is
released once the blood gets out into the tissues. The
more 2,3-DPG in the cell, the more oxygen is delivered
to body tissues. Conversely, the less 2,3-DPG in the
cell, the less oxygen is delivered.
GALE ENCYCLOPEDIA OF MEDICINE

This test requires drawing 5-10 mL of blood.
The patient should not exercise before having the
blood drawn. Exercise increases the body’s need
for oxygen and could cause a temporary increase
in levels of 2,3-DPG.

Aftercare
Discomfort or bruising may occur at the puncture
site, or the person may feel dizzy or faint. Pressure to
the puncture site until the bleeding stops will reduce
bruising. Warm packs to the puncture site will relieve
discomfort.

Normal results
Normal results will vary based on the laboratory
and testing methods used.
3823

2,3-diphosphoglycerate test

Behrman, et al., 16th ed. Philadelphia: W.B. Saunders,
2000, pp. 325-334.

Typhoid fever

KEY TERMS
Anemia—A reduction in the number of erythrocytes or red blood cells. Erythrocytes are necessary
to form hemoglobin for transporting oxygen.
Erythrocytosis—Increased production of red blood
cells.
Hemoglobin—A protein within the red blood cell
that carries oxygen.
Nonspherocytic hemolytic anemia—Anemia
caused by variably shaped red blood cells that
burst, or hemolyze, easily.

Abnormal results
Decreased levels of 2,3-DPG are found in cases of
erythrocytosis and nonspherocytic hemolytic anemia
caused by 2,3-DPG mutase and 2,3-DPG phosphatase
deficiencies. Lower levels are also commonly found
after large blood transfusions.
Increased levels of 2,3-DPG are found in conditions in which the body needs more oxygen, such as
anemia, obstructive lung disease, cystic fibrosis, congenital heart disease, and hyperthyroidism. High altitudes and participating in exercise sessions before the
test can also give false high values.
Resources
PERIODICALS

Hsia, Connie C. W. ‘‘Respiratory Function of
Hemoglobin.’’ New England Journal of Medicine 338
(January 1998): 239-247.

family of bacteria as the type spread by chicken and
eggs, commonly known as salmonella poisoning or
food poisoning. S. typhi bacteria do not have vomiting
and diarrhea as the most prominent symptoms of their
presence in humans. Instead, persistently high fever is
the hallmark of S. typhi infection.

Description
S. typhi bacteria are passed into the stool and
urine of infected patients. They may continue to be
present in the stool of asymptomatic carriers, who are
persons who have recovered from the symptoms of the
disease but continue to carry the bacteria. This carrier
state occurs in about 3% of all individuals recovered
from typhoid fever.
Typhoid fever is passed from person to person
through poor hygiene, such as incomplete or no hand
washing after using the toilet. Persons who are carriers
of the disease and who handle food can be the source
of epidemic spread of typhoid. One such individual
gave her name to the expression ‘‘Typhoid Mary,’’ a
name given to someone whom others avoid.
Typhoid fever is a particularly difficult problem in
parts of the world with poor sanitation practices. There
are about 16 million cases of typhoid reported around
the world each year. In the United States, most patients
who contract typhoid fever have recently returned from
travel to another country where typhoid is much more
common, including Mexico, Peru, Chile, India, and
Pakistan. However, there have been reports in the
early 2000s of typhoid outbreaks within the United
States that were unrelated to recent travel. One such
outbreak occurred in Queens, New York, and was
traced to a worker in a local restaurant.

Nancy J. Nordenson

Causes and symptoms

2,3-DPG see 2,3-diphosphoglycerate test
Tylenol see Acetaminophen
Tympanic membrane perforation see
Perforated eardrum
Tympanometry see Audiometry

Typhoid fever
Definition
Typhoid fever is a severe infection caused by a
bacterium, Salmonella typhi. S. typhi is in the same
3824

S. typhi must be ingested to cause disease.
Transmission often occurs when a person in the carrier
state does not wash hands thoroughly (or not at all)
after defecation and serves food to others. This pathway is sometimes called the fecal-oral route of disease
transmission. In countries where open sewage is accessible to flies, the insects land on the sewage, pick up the
bacteria, and then contaminate food to be eaten by
humans.
After being swallowed, the S. typhi bacteria head
down the digestive tract, where they are taken in by
cells called mononuclear phagocytes. These phagocytes are cells of the immune system, whose job it is
to engulf and kill invading bacteria and viruses. In the
case of S. typhi, however, the bacteria are able to
GALE ENCYCLOPEDIA OF MEDICINE

(Corbis. Reproduced by permission.)

Mary Mallon was born in Cookstown, Ireland, on
September 23, 1869, to Catherine Igo and John Mallon.
As a teenager, Mallon left her parents and immigrated to
New York to live with an aunt and uncle. Until 1906, when
George A. Soper began to study an outbreak of typhoid
fever in Long Island, little was known about Mallon.

Soper was called to identify possible causes of an eruption
of typhoid fever at a summer house in Oyster Bay. After
examining the food and water in a futile attempt to discover contaminants, Soper decided that the disease was
probably transmitted by a human carrier. He soon learned
that the cook had disappeared and tracked Mallon to her
new place of employment, expecting her cooperation in
dealing with the matter. Soper eventually turned the case
over to the New York City Department of Health. When
Mallon was ultimately caught, she refused treatment and
was held for three years as a threat to the public. In 1910, a
judge granted her release with the stipulation that she not
seek employment as a cook, since the disease was transmitted through food. Mallon agreed but, in 1915, an outbreak of typhoid at a hospital was, once again, linked to
her. When Soper investigated this incident he learned that
employees had nicknamed one of the cooks ‘‘Typhoid
Mary.’’
After Mallon was found, she was taken into custody,
and spent the rest of her life at Riverside Hospital. Mallon
died on November 11, 1938.

of bacteria fill an individual phagocyte, they spill out of
the cell and into the bloodstream, where their presence
begins to cause symptoms.
The presence of increasingly large numbers of bacteria in the bloodstream (bacteremia) is responsible for
an increasingly high fever, which lasts throughout the
four to eight weeks of the disease in untreated individuals. Other symptoms of typhoid fever include constipation (at first), extreme fatigue, headache, joint pain,
and a rash across the abdomen known as rose spots.

Transmission electron microscopy (TEM) scan of Salmonella
typhi, the bacteria which causes typhoid fever in humans.
(Custom Medical Stock Photo. Reproduced by permission.)

survive ingestion by the phagocytes, and multiply within
these cells. This period of time, during which the bacteria
are multiplying within the phagocytes, is the 10 to 14-day
incubation period of typhoid fever. When huge numbers
GALE ENCYCLOPEDIA OF MEDICINE

The bacteria move from the bloodstream into
certain tissues of the body, including the gallbladder
and lymph tissue of the intestine (called Peyer’s
patches). The tissue’s response to this invasion causes
symptoms ranging from inflammation of the gallbladder (cholecystitis) to intestinal bleeding to actual perforation of the intestine. Perforation of the intestine
refers to an actual hole occurring in the wall of the
intestine, with leakage of intestinal contents into the
abdominal cavity. This leakage causes severe irritation
and inflammation of the lining of the abdominal
cavity, which is called peritonitis. Peritonitis is a frequent cause of death from typhoid fever.
Other complications of typhoid fever include liver
and spleen enlargement, sometimes so great that the
spleen ruptures or bursts; anemia, or low red blood cell
3825

Typhoid fever

M A R Y M A L L O N (1869–1938)

Typhoid fever

KEY TERMS
Asymptomatic—A state in which a person experiences no symptoms of a disease.
Bacteremia—Bacteria in the blood.
Carrier—A person who has a particular disease
agent present within his/her body, and can pass
this agent on to others, but who displays no symptoms of infection.
Epidemic—A large number of cases of the same
disease or infection all occurring within a short
time period in a specific location.
Mononuclear phagocyte—A type of cell of the
human immune system that ingests bacteria,
viruses, and other foreign matter, thus removing
potentially harmful substances from the bloodstream. These substances are usually then digested
within the phagocyte.
Rose spots—A pinkish rash across the trunk or
abdomen that is a classic sign of typhoid fever.

count due to blood loss from the intestinal bleeding; joint
infections, which are especially common in patients with
sickle cell anemia and immune system disorders; pneumonia caused by a bacterial infection– usually
Streptococcus pneumoniae– which is able to take hold
due to the patient’s weakened state; heart infections; and
meningitis and infections of the brain, which cause mental confusion and even coma. It may take a patient
several months to recover fully from untreated typhoid
fever.

Diagnosis
In some cases, the doctor may suspect the diagnosis if the patient has already developed the characteristic rose spots, or if he or she has a history of recent
travel in areas with poor sanitation. The diagnosis,
however, is confirmed by a blood culture. Samples of
a patient’s stool, urine, and bone marrow can also be
used to grow S. typhi in a laboratory for identification
under a microscope. Cultures are the most accurate
method of diagnosis. Blood cultures usually become
positive in the first week of illness in 80% of patients
who have not taken antibiotics.

Treatment
Antibiotics are the treatment of choice for typhoid
fever. As of the early 2000s, the most frequently used
3826

drugs are ceftriaxone and cefoperazone. Ciprofloxacin
is sometimes given as follow-up therapy.
Carriers of S. typhi must be treated even when
they do not show any symptoms of the infection,
because carriers are responsible for the majority of
new cases of typhoid fever. Eliminating the carrier
state is actually a fairly difficult task. It requires treatment with one or even two different medications over
a period of four to six weeks. The antibiotics most
commonly given are ampicillin (sometimes given
together with probenecid) and amoxicillin. In the
case of a carrier with gallstones, surgery may need to
be performed to remove the gallbladder. This measure
is necessary because typhoid bacteria are often housed
in the gallbladder, where they may survive in spite of
antibiotic treatment. In some patients, however, treatment with rifampin and trimethoprim-sulfamethoxazole is sufficient to eradicate the bacteria from the
gallbladder without surgery.

Prognosis
The prognosis for recovery is good for most
patients. In the era before effective antibiotics were
discovered, about 12% of all typhoid fever patients
died of the infection. Now, however, fewer than 1% of
patients who receive prompt antibiotic treatment will
die. The mortality rate is highest in the very young and
very old, and in patients suffering from malnutrition.
The most ominous signs are changes in a patient’s
state of consciousness, including stupor or coma.

Prevention
Hygienic sewage disposal systems in a community
as well as proper personal hygiene are the most important factors in preventing typhoid fever.
Immunizations are available for travelers who expect
to visit countries where S. typhi is a known public
health problem. Some of these immunizations provide
only short-term protection (for a few months), while
others may be effective for several years. Efforts are
being made to develop vaccines that provide a longer
period of protection with fewer side effects from the
vaccine itself. The most commonly reported side
effects are flu-like muscle cramps and abdominal
pain. As of earlt 2004, these vaccines are also being
studied as possible antibioterrorism agents.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD.,
editors. ‘‘Enterobacteriaceae Infections.’’ In The
GALE ENCYCLOPEDIA OF MEDICINE

PERIODICALS

Begier, E. M., D. R. Burwen, P. Haber, et al. ‘‘Postmarketing
Safety Surveillance for Typhoid Fever Vaccines from the
Vaccine Adverse Event Reporting System, July 1990
through June 2002.’’ Clinical Infectious Diseases 38 (March
15, 2004): 771–779.
Parry, C. M. ‘‘Typhoid Fever.’’ Current Infectious Diseases
Report 6 (February 2004): 27–33.
Yoon, J., S. Segal-Maurer, and J. J. Rahal. ‘‘An Outbreak of
Domestically Acquired Typhoid Fever in Queens,
NY.’’ Archives of Internal Medicine 164 (March 8,
2004): 565–567.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

Typhus
Definition
Several different illnesses are called ‘‘typhus,’’ all
of them caused by one of the bacteria in the family
Rickettsiae. Each illness occurs when the bacteria is
passed to a human through contact with an infected
insect.

Description
The four main types of typhus are:


epidemic typhus



Brill-Zinsser disease



endemic or murine typhus



scrub typhus

These diseases are all somewhat similar,
although they vary in terms of severity. The specific
type of Rickettsia that causes the disease also varies,
as does the specific insect that can pass the bacteria
along.
Epidemic typhus, which is sometimes called jail
fever or louse-borne typhus, is caused by Rickettsia
prowazekii, which is carried by body lice. When the lice
feed on a human, they may simultaneously defecate.
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When the person scratches the bite, the feces (which
carrys the bacteria) are scratched into the wound.
Body lice are common in areas in which people live
in overcrowded, dirty conditions, with few opportunities to wash themselves or their clothing. Because of
this fact, this form of typhus occurs simultaneously in
large numbers of individuals living within the same
community; that is, in epidemics. This type of typhus
occurs when cold weather, poverty, war, and other
disasters result in close living conditions that encourage the maintenance of a population of lice living
among humans. Some medical historians think that
the Great Plague of Athens in 430 B.C. may have been
epidemic typhus. Epidemic typhus is now found in
the mountainous regions of Africa, South America,
and Asia.
Brill-Zinsser disease is a reactivation of an earlier
infection with epidemic typhus. It affects people years
after they have completely recovered from epidemic
typhus. When something causes a weakening of their
immune system (like aging, surgery, illness), the bacteria can gain hold again, causing illness. This illness
tends to be extremely mild.
Endemic typhus is carried by fleas. When a flea
lands on a human, it may defecate as it feeds. When the
person scratches the itchy spot where the flea was
feeding, the bacteria-laden feces are scratched into
the skin, thus causing infection. The causative bacteria
is called Rickettsia typhi. Endemic typhus occurs most
commonly in warm, coastal regions. In the United
States, southern Texas and southern California have
the largest number of cases.
Scrub typhus is caused by Rickettsia tsutsugamushi. This bacteria is carried by mites or chiggers.
As the mites feed on humans, they deposit the bacteria. Scrub typhus occurs commonly in the southwest
Pacific, southeast Asia, and Japan. It is a very common cause of illness in people living in or visiting these
areas. It occurs more commonly during the wet
season.

Causes and symptoms
The four types of typhus cause similar types of
illnesses, though varying in severity.
Epidemic typhus causes fever, headache, weakness, and muscle aches. It also causes a rash composed
of both spots and bumps. The rash starts on the back,
chest, and abdomen, then spreads to the arms and legs.
The worst types of complications involve swelling in
the heart muscle or brain (encephalitis). Without treatment, this type of typhus can be fatal.
3827

Typhus

Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.

Typhus

Prognosis

KEY TERMS
Antibody—Specialized cells of the immune system, which can recognize organisms that invade
the body (such as bacteria, viruses, and fungi).
The antibodies are then able to set off a complex chain of events designed to kill these foreign invaders.
Bioterrorism—The use of disease microorganisms
to intimidate or terrorize a civilian population.
Endemic—Occurring naturally and consistently in
a particular area.
Epidemic—A large cluster of cases all occurring at
about the same time within a specific community
or region.

Brill-Zinsser disease is quite mild, resulting in
about a week-long fever, and a light rash similar to
that of the original illness.
Endemic typhus causes about 12 days of high fever,
with chills and headache. A light rash may occur.
Scrub typhus causes a wide variety of effects. The
main symptoms include fever, headache, muscle aches
and pains, cough, abdominal pain, nausea and vomiting, and diarrhea. Some patients experience only these
symptoms. Some patients develop a rash, which can be
flat or bumpy. The individual spots eventually develop
crusty black scabs. Other patients go on to develop a
more serious disease, in which encephalitis, pneumonia, and swelling of the liver and spleen (hepatosplenomegaly) occur.

Diagnosis
A number of tests exist that can determine the
reactions of a patient’s antibodies (immune cells in
the blood) to the presence of certain viral and bacterial
markers. When the antibodies react in a particular
way, it suggests the presence of a rickettsial infection.
Many tests require a fair amount of time for processing, so practitioners will frequently begin treatment
without completing tests, simply on the basis of a
patient’s symptoms.

Treatment
The antibiotics tetracycline or chloramphenicol
are used for treatment of each of the forms of typhus.
3828

The prognosis depends on what types of complications an individual patient experiences. While children usually recover well from epidemic typhus, older
adults may have as much as a 60% death rate without
treatment. Brill-Zinsser, on the other hand, carries no
threat of death. People usually recover uneventfully
from endemic typhus, although the elderly, those with
other medical problems, or people mistakenly treated
with sulfa drugs may have a 1% death rate from the
illness. Scrub typhus responds well to appropriate
treatment, but untreated patients have a death rate
of about 7%.
The relatively high death rate from untreated
typhus is one reason why some researchers are concerned that its causative organisms might be used in
the future as agents of bioterrorism.

Prevention
Prevention for each of these forms of typhus
includes avoidance of the insects that carry the causative bacteria. Other preventive measures include good
hygiene and the use of insect repellents.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Epidemic Tyhpus.’’ In The Merck Manual of
Diagnosis and Therapy. Whitehouse Station, NJ:
Merck Research Laboratories, 2004.
PERIODICALS

Cunha, B. A. ‘‘The Cause of the Plague of Athens: Plague,
Typhoid, Typhus, Smallpox, or Measles?’’ Infectious
Diseases Clinics of North America 18 (March 2004):
29–43.
Ge, H., Y. Y. Chuang, S. Zhao, et al. ‘‘Comparative
Genomics of Rickettsia prowazekii Madrid E and Breinl
Strains.’’ Journal of Bacteriology 186 (January 2004):
556–565.
Raoult, D., T. Woodward, and J. S. Dumler.
‘‘The History of Epidemic Typhus.’’ Infectious
Diseases Clinics of North America 18 (March 2004):
127–140.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Tzanck preparation is a rapid test done to diagnose infections caused by herpesviruses. Cells are
examined under a microscope for signs of infection.

Purpose
Herpesviruses are responsible for several superficial infections. Varicella zoster virus causes chickenpox and shingles, herpes simplex type 1 causes the
common cold sore or fever blister, and herpes simplex
type 2 causes the sexually transmitted disease genital
herpes. They are all characterized by blisters and
ulcers.
Physicians usually can diagnose herpes infections
simply by looking at the type of blisters and ulcers, and
their distribution on the person’s body. Sometimes
laboratory evidence of herpes is needed to confirm
the diagnosis. For example, herpes can be devastating
to a newborn baby or a person with a weakened
immune system. Treatment can begin once herpes is
confirmed in a laboring mother’s genital ulcers or in
the skin blisters of an immunocompromised person. A
lab tries to grow (culture) the virus that may be present
in the blister. This lab test takes several days to complete, but the Tzanck preparation takes minutes.

Description
The Tzanck preparation is done by smearing cells
taken from a fresh blister or ulcer onto a microscope
slide. The cells are stained with a special stain, such as
Wright’s stain, and then examined under a microscope
for characteristic changes caused by a herpesvirus.
Herpes causes giant cells with multiple nuclei. The
shape of each nucleus appears molded to fit together
with those adjacent. The background of the cell looks
like ground glass and contains small dark spots called
inclusion bodies.
Tzanck preparation is also called a Tzanck smear,
herpes stain for inclusion bodies, or inclusion bodies
stain. Results are available the same or following day,
often within minutes.

GALE ENCYCLOPEDIA OF MEDICINE

Herpes—A family of viruses including herpes simplex types 1 and 2, and herpes zoster (also called
varicella zoster). Herpes viruses cause several
infections, all characterized by blisters and ulcers,
including chickenpox, shingles, genital herpes, and
cold sores or fever blisters.

Preparation
A fresh blister is opened with a scalpel or
sterile needle. The physician scrapes the base of
the blister with the scalpel, gathers as much cellular
material as possible, and gently spreads it on a
microscope slide.

Normal results
A normal smear shows no evidence of a herpes
infection. This test may also have false negatives.
Studies have shown that the Tzanck preparation
shows signs of infection in only 50–79% of people
with a herpes infection. A negative Tzanck preparation may have to be confirmed by a herpes culture.

Abnormal results
A smear that shows evidence of herpes infection does
not distinguish between the various infections caused by
herpes virus. The physician uses the person’s symptoms
and other clinical findings to distinguish between these
infections. In certain cases, the physician will follow a
positive Tzanck smear with a culture for confirmation.
Resources
BOOKS

Henry, John B., editor. Clinical Diagnosis and Management
by Laboratory Methods. 19th ed. Philadelphia: W. B.
Saunders Co., 1996.

Nancy J. Nordenson

Tzanck smear see Tzanck preparation

3829

Tzanck preparation

KEY TERMS

Tzanck preparation

U

Ulcer surgery
Definition
Ulcer surgery is a procedure used to cure peptic
ulcer disease when medications have failed.

Purpose
Ulcer surgery is used to relieve a present peptic
ulcer disease and to prevent recurrence of it.

Description
The two primary goals of ulcer surgery, elimination
of the current problem and prevention of future problems bring with them a third problem—to perpetuate
the normal function of the bowel. The vagus nerves
relax the pylorus, allowing the stomach to empty.
Cutting the vagus nerves, while reducing the stomach’s
acid production, also prevents stomach emptying.
Therefore, the procedures described must guarantee
stomach emptying along with their other goals.

Surgery is usually required if the ulcer is in one of
the following states:


perforated and overflowed into the abdomen



scarred or swelled so much that the bowel is
obstructed



acute bleeding



defied all other types of treatment

The need for ulcer surgery has diminished greatly
over the past 20–30 years due to the discovery of two
new classes of drugs and the presence of the causal
germ Helicobacter pylori in the stomach. The drugs are
the H2 blockers such as cimetidine and ranitidine and
the proton pump inhibitors such as omeprazole. These
effectively arrest acid production. H. pylori can be
eliminated from most patients with a combination of
antibiotics and bismuth.

Total gastrectomy
Removing the entire stomach is done only for resistant Zollinger-Ellison syndrome or extensive cancers.
Antrectomy
The lower half of the stomach makes most of the
acid and gets all the peptic ulcers above the duodenum. Removing it leaves little place for ulcers to form
and little acid to produce them.
Vagotomy
Cutting the vagus nerves can be done in three
ways:


the main nerves can be cut completely as they enter
the abdomen from the chest



the branches that go to the stomach can be cut as
they leave the main nerves



the tiny branches that stimulate acid production can
be cut on the surface of the stomach

Precautions
There is a tumor of the pancreas that produces a
hormone called gastrin. Gastrin causes ulcers by stimulating acid production. If this disease—Zollinger-Ellison
syndrome—does not respond to medical treatment,
either the tumor or the entire stomach must be
removed.
GALE ENCYCLOPEDIA OF MEDICINE

Pyloroplasty
Opening up the valve at the outlet of the stomach
guarantees that the stomach can empty, even without
3831

Ulcer surgery

Esophagus

Duodenal ulcer

Duodenum

Peptic ulcer

Marginal ulcer

Common sites of ulcers in the human stomach. The need for ulcer surgery has diminished over the past 20-30 years due to the
discovery that Helicobacter pylori, an infectious bacterium, plays a major role in causing ulcers. H. pylori can be eliminated from
most patients with a combination of antibiotics and bismuth. (Illustration by Electronic Illustrators Group.)

vagus nerve stimulation. Pyloroplasty is ordinarily
done by cutting across the muscle that surrounds the
outlet. It can also be done by passing a balloon down
from the mouth and inflating it forcefully to stretch
out the pylorus (opening from the stomach to the
intestine).

A selective vagotomy can be done alone. A complete vagotomy requires either a pyloroplasty or
antrectomy. An antrectomy must be reconnected
with either a Billroth I or a Billroth II.
Some of these procedures are now being done
through a laparoscope.

Close perforation
For some patients all that can be done is to close
the hole in the bowel and wait for the patient to
recover before initiating corrective surgery.
Billroth I and II
After removing a piece of the stomach, the
remainder must be reattached to the rest of the
bowel. Simply joining the upper stomach back to
the duodenum is called a Billroth I or gastroduodenostomy. It is sometimes better to attach the stomach
with another piece of bowel (the jejunum), creating a
‘‘y’’ with the bile drainage and the duodenum forming
the second branch of the ‘‘y.’’ This part of the procedure
is called a gastrojejunostomy. A gastroenterostomy is a
more general term for connecting the stomach with any
piece of bowel.
3832

Risks
All of these procedures carry risks, generally in
proportion to their benefits. The more extensive surgeries such as vagotomy and antrectomy with Billroth
II reconnection have the highest success rate and the
highest complication rate.
Complications include:


Diarrhea after a meal



Dumping syndrome occurring after a meal and characterized by sweating, abdominal pain, vomiting,
lightheadedness, and diarrhea



Hypoglycemia after a meal



Alkaline reflux gastritis marked by abdominal pain,
vomiting of bile, diminished appetite, and irondeficiency anemia
GALE ENCYCLOPEDIA OF MEDICINE

Gastrin—A type of hormone that produces gastric
juice.
Hypoglycemia—An abnormal decrease in blood
sugar level.
Jejunum—Section of the small intestine.
Laparoscope—A pencil-thin telescope that allows
surgery to be done through half-inch incisions.
Pylorus—The opening from the stomach to the
intestine.
Vagus nerve—Cranial nerves that supply the internal organs (viscera).
Zollinger-Ellison syndrome—A syndrome marked
by peptic ulcers and gastrinomas in the pancreas.



Recurrence of an ulcer



Malabsorption of necessary nutrients, especially
iron, in patients who have had all or part of their
stomachs removed

Resources
BOOKS

Moody, Frank G., et al. ‘‘Stomach.’’ In Sleisenger &
Fordtran’s Gastrointestinal and Liver Disease, edited by
Mark Feldman, et al. Philadelphia: W. B. Saunders Co.,
1998.

J. Ricker Polsdorfer, MD

Ulcerative colitis
Definition
Ulcerative colitis is a form of inflammatory bowel
disease (IBD). It causes swelling, ulcerations, and loss
of function of the large intestine.

Description
The primary problem in IBD is inflammation, as
the name suggests. Inflammation is a process that
often occurs in order to fight off foreign invaders in
the body, including viruses, bacteria, and fungi. In
response to such organisms, the body’s immune system begins to produce a variety of cells and chemicals
intended to stop the invasion. These immune cells and
GALE ENCYCLOPEDIA OF MEDICINE

chemicals, however, also have direct effects on the
body’s tissues, resulting in heat, redness, swelling,
and loss of function. No one knows what starts the
cycle of inflammation in IBD, but the result is a swollen, boggy intestine.
In ulcerative colitis, the inflammation affects the
lining of the rectum and large intestine. It is thought
that the inflammation begins in the last segment of the
large intestine, which empties into the rectum (sigmoid
colon). This inflammation may spread through the
entire large intestine, but only rarely affects the very
last section of the small intestine (ileum). The rest of
the small intestine remains normal.
Ulcerative colitis differs from Crohn’s disease,
which is a form of IBD that affects both the small
and large intestines. The inflammation of ulcerative
colitis occurs only in the lining of the intestine (unlike
Crohn’s disease which affects all of the layers of the
intestinal wall). As the inflammation continues, the
tissue of the intestine begins to slough off, leaving
pits (ulcerations) which often become infected.
Like Crohn’s disease, ulcerative colitis occurs in
all age groups, with the most common age of diagnosis
being 15–35 years of age. Men and women are affected
equally. Whites are more frequently affected than
other racial groups, and people of Jewish origin have
3–6 times greater likelihood of suffering from any
IBD. IBD is familial; an IBD patient has a 20% chance
of having other relatives who are fellow sufferers.

Causes and symptoms
No specific cause of ulcerative colitis has been
identified. Although no organism (virus, bacteria, or
fungi) has been found to set off the cycle of inflammation that occurs in ulcerative colitis, some researchers
continue to suspect that some such organism is responsible for initiating the cycle. Other researchers are concentrating on identifying some change in the cells of the
colon that would make the body’s immune system
accidentally begin treating those cells as foreign invaders. Other evidence for such a disorder of the immune
system includes the high number of other immune disorders that tend to accompany ulcerative colitis.
The first symptoms of ulcerative colitis are
abdominal cramping and pain, a sensation of urgent
need to have a bowel movement (defecate), and blood
and pus in the stools. Some patients experience diarrhea, fever, and weight loss. If the diarrhea continues,
signs of severe fluid loss (dehydration) begin to appear,
including low blood pressure, fast heart rate, and
dizziness.
3833

Ulcerative colitis

KEY TERMS

Ulcerative colitis

Patients with ulcerative colitis also have a high
chance of experiencing other disorders, including
inflammation of the joints (arthritis), inflammation
of the vertebrae (spondylitis), ulcers in the mouth
and on the skin, the development of painful, red
bumps on the skin, inflammation of several areas of
the eye, and various disorders of the liver and
gallbladder.

Diagnosis

A specimen of a colon indicating ulcerative colitis. (Photo
Researchers, Inc. Reproduced by permission.)

Severe complications of ulcerative colitis include
perforation of the intestine (in which the wall of the
intestine develops a hole), toxic dilation of the colon
(in which the colon become quite large in diameter),
and the development of colon cancer.
Intestinal perforation occurs when long-standing
inflammation and ulceration of the intestine weakens
the wall to such a degree that a hole occurs. This is a
life-threatening complication, because the contents of
the intestine (which under normal conditions contains
a large number of bacteria) spill into the abdomen.
The presence of bacteria in the abdomen can result in a
massive infection called peritonitis.
Toxic dilation of the colon is thought to occur
because the intestinal inflammation interferes with
the normal function of the muscles of the intestine.
This allows the intestine to become lax, and its diameter begins to increase. The enlarged diameter thins
the walls further, increasing the risk of perforation and
peritonitis. When the diameter of the intestine is quite
large, and infection is present, the condition is referred
to as ‘‘toxic megacolon.’’
Patients with ulcerative colitis have a significant
risk of developing colon cancer. This risk seems to
begin around 10 years after diagnosis of ulcerative
colitis. The risk becomes statistically greater every
year:


At 10 years, the risk of cancer is about 0.5–1%.



At 15 years, the risk of cancer is about 12%.



At 20 years, the risk of cancer is about 23%.



At 24 years, the risk of cancer is about 42%.

The overall risk of developing cancer seems to be
greatest for those patients with the largest extent of
intestine involved in ulcerative colitis.
3834

Diagnosis is first suspected based on the symptoms
that a patient is experiencing. Examination of the stool
will usually reveal the presence of blood and pus (white
blood cells). Blood tests may show an increase in the
number of white blood cells, which is an indication of
inflammation occurring somewhere in the body. The
blood test may also reveal anemia, particularly when a
great deal of blood has been lost in the stool.
The most important method of diagnosis is endoscopy, during which a doctor passes a flexible tube
with a tiny, fiberoptic camera device through the rectum and into the colon. The doctor can then examine
the lining of the intestine for signs of inflammation
and ulceration that might indicate ulcerative colitis. A
tiny sample (biopsy) of the intestine will be removed
through the endoscope, which will be examined under
a microscope for evidence of ulcerative colitis. Because
of the increased risk of cancer in patients with ulcerative colitis, endoscopic exam will need to be repeated
frequently. Biopsies should be taken regularly, to closely monitor the intestine for the development of cancer or precancerous changes.
X-ray examination is helpful to determine the
amount of intestine affected by the disease. However,
x-ray examinations requiring the use of barium should
be delayed until treatment has begun. Barium is a
chalky solution that the patient drinks or is administered through the rectum and into the intestine
(enema). The presence of barium in the intestine
allows more detail to be seen on x-ray pictures.
However, because of the risk of intestinal perforation
in ulcerative colitis, most doctors begin treatment
before stressing the wall of the intestine with the barium solution.

Treatment
Treatment for ulcerative colitis addresses the
underlying inflammation, as well as the problems
occurring due to continued diarrhea and blood loss.
Inflammation is treated with a drug called sulfasalazine. Sulfasalazine is made up of two parts. One
GALE ENCYCLOPEDIA OF MEDICINE

Endoscopy—A type of medical examination in
which an instrument called an endoscope is passed
into an area of the body (the bladder or intestine, for
example). The endoscope usually has a fiberoptic
camera, which allows a greatly magnified image to
be projected onto a video screen, to be viewed by
the operator. Many endoscopes also allow the
operator to retrieve a small sample (biopsy) of the
area being examined, in order to more closely view
the tissue under a microscope.
Immune system—The system of the body that is
responsible for producing various cells and chemicals that fight off infection by viruses, bacteria,
fungi, and other foreign invaders. In autoimmune
disease, these cells and chemicals are turned
against the body itself.
Inflammation—The result of the body’s attempts to
fight off and wall off an area that is infected.
Inflammation results in the classic signs of redness,
heat, swelling, and loss of function.

part is related to the sulfa antibiotics; the other part
is a form of the anti-inflammatory chemical salicylic
acid (related to aspirin). Sulfasalazine is not wellabsorbed from the intestine, so it stays mostly within
the intestine, where it is broken down into its components. It is believed to be primarily the salicylic acid
component that is active in treating ulcerative colitis,
by fighting inflammation. For patients who do not
respond to sulfasalazine, steroid medications (such as
prednisone) are the next choice.
Depending on the degree of blood loss, a patient
with ulcerative colitis may require blood transfusions and fluid replacement through a needle in
the vein (intravenous or IV). Medications that can
slow diarrhea must be used with great care, because
they may actually cause the development of toxic
megacolon.
A patient with toxic megacolon requires close
monitoring and care in the hospital. He or she will
usually be given steroid medications through an IV,
and may be put on antibiotics. If these measures do
not improve the situation, the patient will have to
undergo surgery to remove the colon. This is done
because the risk of death after perforation of toxic
megacolon is greater than 50%.
Similarly, a patient with proven cancer of the
colon, or even a patient who shows certain signs
GALE ENCYCLOPEDIA OF MEDICINE

thought to indicate a precancerous condition, will
need his or her colon removed. Removal of the
colon is called a colectomy. When a colectomy is
performed, a piece of the small intestine (ileum) is
pulled through an opening in the abdomen. This bit
of intestine is fashioned surgically to allow a special
bag to be placed over it, in order to catch the body’s
waste (feces) which no longer can be passed through
the large intestine and out of the anus. This opening,
which will remain for the duration of the patient’s life,
is called an ileostomy.

Prognosis
Remission refers to a disease becoming inactive
for a period of time. The rate of remission of ulcerative
colitis (after a first attack) is nearly 90%. Those individuals whose colitis is confined primarily to the left
side of the large intestine have the best prognosis.
Those individuals with extensive colitis, involving
most or all of the large intestine, have a much poorer
prognosis. Recent studies show that about 10% of
these patients will have died by 10 years after diagnosis. About 20–25% of all ulcerative colitis patients will
require colectomy. Unlike the case for patients with
Crohn’s disease, however, such radical surgery results
in a cure of the disease.
Resources
ORGANIZATIONS

Crohn’s and Colitis Foundation of America, Inc. 386 Park
Avenue South, 17th Floor, New York, NY 10016-8804.
(800) 932-2423.

Rosalyn Carson-DeWitt, MD

Ulcers (digestive)
Definition
In general, an ulcer is any eroded area of skin or a
mucous membrane, marked by tissue disintegration.
In common usage, however, ulcer usually is used to
refer to disorders in the upper digestive tract. The
terms ulcer, gastric ulcer, and peptic ulcer often are
used loosely and interchangeably. Peptic ulcers can
develop in the lower part of the esophagus, the stomach, the first part of the small intestine (the duodenum), and the second part of the small intestine (the
jejunum).
3835

Ulcers (digestive)

KEY TERMS

Ulcers (digestive)

Description
It is estimated that 2% of the adult population in
the United States has active peptic ulcers, and that
about 10% will develop ulcers at some point in their
lives. There are about 500,000 new cases of peptic ulcer
in the United States every year, with as many as 4
million recurrences. The male/female ratio for ulcers
of the digestive tract is 3:1.
The most common forms of peptic ulcer are duodenal and gastric. About 80% of all ulcers in the
digestive tract are duodenal ulcers. This type of ulcer
may strike people in any age group but is most common in males between the ages of 20 and 45. The
incidence of duodenal ulcers has dropped over the
past 30 years. Gastric ulcers account for about 16%
of peptic ulcers. They are most common in males
between the ages of 55 and 70. The single most common cause of gastric ulcers is the use of nonsteroidal
anti-inflammatory drugs, or NSAIDs. The widespread
use of NSAIDs is thought to explain why the incidence
of gastric ulcers in the United States is rising.

Causes and symptoms
Causes of peptic ulcers
There are three major causes of peptic ulcers:
infection, certain types of medication, and disorders
that cause oversecretion of stomach juices.
HELICOBACTER PYLORI INFECTION. Helicobacter
pylori is a rod-shaped gram-negative bacterium that
lives in the mucous tissues that line the digestive tract.
Infection with H. pylori is the most common cause of
duodenal ulcers. About 95% of patients with duodenal ulcers are infected with H. pylori, as opposed to
only 70% of patients with gastric ulcers.
USE OF NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS (NSAIDS). Nonsteroidal anti-inflammatory

drugs, or NSAIDs, are painkillers that many people
use for headaches, sore muscles, arthritis, menstrual
cramps, and similar complaints. Many NSAIDs are
available without prescriptions. Common NSAIDs
include aspirin, ibuprofen (Advil, Motrin), flurbiprofen
(Ansaid, Ocufen), ketoprofen (Orudis), and indomethacin (Indacin). Chronic NSAID users have 40
times the risk of developing a gastric ulcer as nonusers.
Users also are three times more likely than nonusers to
develop bleeding or fatal complications of ulcers.
Aspirin is the NSAID that is most likely to cause ulcers.
MISCELLANEOUS
SYNDROMES
AND
DISORDERS. Fewer than 5% of peptic ulcers are due

to these disorders. They include Zollinger-Ellison
3836

syndrome, a disorder in which small tumors, called
gastrinomas, secrete a hormone (gastrin) that stimulates the production of digestive juices. Because of this
excess secretion, these disorders are sometimes called
hypersecretory syndromes.
OTHER RISK FACTORS. Smoking is an important
risk factor that increases a patient’s chance of developing an ulcer, decreases the body’s response to therapy,
and increases the chances of dying from ulcer complications. Blood type appears to be a predisposing factor
for ulcer location; people with type A blood are more
likely to have gastric ulcers, while those with type O are
more likely to develop duodenal ulcers. The role of
emotional stress in ulcer development is currently
debated. Present research indicates that an individual’s
attitudes toward stress, rather than the amount of
stress by itself, is a better predictor of vulnerability to
peptic ulcers. Preferences for high-fat or spicy foods do
not appear to be significant risk factors.

Symptoms
GASTRIC ULCERS. The symptoms of gastric ulcers
include feelings of indigestion and heartburn, weight
loss, and repeated episodes of gastrointestinal bleeding. Ulcer pain often is described as gnawing, dull,
aching, or resembling hunger pangs. The patient may
be nauseated and suffer loss of appetite. About 30% of
patients with gastric ulcers are awakened by pain at
night. Many patients have periods of chronic ulcer
pain alternating with symptom-free periods that last
for several weeks or months. This characteristic is
called periodicity.
DUODENAL ULCERS. The symptoms of duodenal
ulcers include heartburn, stomach pain relieved by
eating or antacids, weight gain, and a burning sensation at the back of the throat. The patient is most likely
to feel discomfort two to four hours after meals, or
after having citrus juice, coffee, or aspirin. About 50%
of patients with duodenal ulcers awake during the
night with pain, usually between midnight and three
a.m. A regular pattern of ulcer pain associated with
certain periods of day or night or a time interval after
meals is called rhythmicity.

Not all digestive ulcers produce symptoms; as
many as 20% of ulcer patients have so-called painless
or silent ulcers. Silent ulcers occur most frequently in
the elderly and in chronic NSAID users.
Complications
Between 10–20% of peptic ulcer patients develop
complications at some time during the course of their
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Physical examination and patient history

A clinical photograph of a large duodenal ulcer after surgical
removal. The ulcer is the prominent triangular crater at center. (Photo Researchers, Inc. Reproduced by permission.)

illness. All of these are potentially serious conditions.
Complications are not always preceded by diagnosis
of or treatment for ulcers; as many as 60% of patients
with complications have not had prior symptoms.
HEMORRHAGE. Bleeding is the most common
complication of ulcers. It may result in anemia, vomiting blood (hematemesis), or the passage of bright red
blood through the rectum (melena). About half of all
cases of bleeding from the upper digestive tract are
caused by ulcers. The mortality rate from ulcer hemorrhage is 6–10%.
PERFORATION. About 5% of ulcer patients
develop perforations, which are holes in the duodenal
or gastric wall through which the stomach contents
can leak out into the abdominal cavity. The incidence
of perforation is rising because of the increased use of
NSAIDs, particularly among the elderly. The signs of
an ulcer perforation are severe pain, fever, and tenderness when the doctor touches the abdomen. Most
cases of perforation require emergency surgery. The
mortality rate is about 5%.
PENETRATION. Ulcer penetration is a complication in which the ulcer erodes through the intestinal
wall without digestive fluid leaking into the abdomen.
Instead, the ulcer penetrates into an adjoining organ,
such as the pancreas or liver. The signs of penetration
are more severe pain without rhythmicity or periodicity, and the spread of the pain to the lower back.
OBSTRUCTION. Obstruction of the stomach outlet
occurs in about 2% of ulcer patients. It is caused by
swelling or scar tissue formation that narrows the
opening between the stomach and the duodenum
(the pylorus). Over 90% of patients with obstruction
have recurrent vomiting of partly digested or

GALE ENCYCLOPEDIA OF MEDICINE

The diagnosis of peptic ulcers should rarely be
made on the basis of a physical examination alone.
However, a 2003 report showed that many ulcer
diagnoses made based solely on physical exams
actually are only dyspepsia, or upper adnominal
pain and discomfort not caused by ulcers. The
only significant finding may be mild soreness in
the area over the stomach when the doctor presses
(palpates) it. The doctor is more likely to suspect an
ulcer if the patient has one or more of the following
risk factors:


male sex



age over 45



recent weight loss, bleeding, recurrent vomiting,
jaundice, back pain, or anemia



history of using aspirin or other NSAIDs



history of heavy smoking



family history of ulcers or stomach cancer
Endoscopy and imaging studies

An endoscopy is considered the best procedure for
diagnosing digestive ulcers and for taking samples of
stomach tissue for biopsies. An endoscope is a slender
tube-shaped instrument that allows the doctor to view
the tissues lining the stomach and duodenum.
Duodenal ulcers are rarely malignant. If the ulcer is
in the stomach, however, the doctor will take a tissue
sample because 3–5% of gastric ulcers are malignant.
Radiological studies are sometimes used instead of
endoscopy because they are less expensive, more comfortable for the patient, and are 85% accurate in
detecting malignancies.
Laboratory tests
BLOOD TESTS. Blood tests usually give normal
results in ulcer patients without complications. They
are useful, however, in evaluating anemia from a
bleeding ulcer or a high white cell count from perforation or penetration. Serum gastrin levels can be used to
screen for Zollinger-Ellison syndrome.
TESTS FOR HELICOBACTER PYLORI. It is important to test for H. pylori because almost all ulcer
patients who are not taking NSAIDs are infected.

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Ulcers (digestive)

undigested food; 20% are seriously dehydrated.
These patients also usually feel full after eating only
a little food, and may lose weight.

Ulcers (digestive)

KEY TERMS

A barium x-ray image of a gastric ulcer. (Photograph by Bates,
M.D., Custom Medical Stock Photo. Reproduced by permission.)

Noninvasive tests include blood tests for immune
response and a breath test. In the breath test, the
patient is given an oral dose of radiolabeled urea.
If H. pylori is present, it will react with the urea
and the patient will exhale radiolabeled carbon dioxide. Invasive tests for H. pylori include tissue biopsies and cultures performed from fluid obtained by
endoscopy.

Duodenum—The first of the three segments of the
small intestine. The duodenum connects the stomach and the jejunum. Most peptic ulcers are in
the duodenum.
Helicobacter pylori—A gram-negative rodshaped bacterium that lives in the tissues of the
stomach and causes inflammation of the stomach
lining.
Zollinger-Ellison syndrome—A disorder characterized by the presence of tumors (gastrinomas) that
secrete a hormone (gastrin), which stimulates the
production of digestive juices.

Surgery
Surgical treatment of ulcers is generally used only
for complications and suspected malignancies. The
most common surgical procedures that are used are
vagotomies, in which the connections of the vagus
nerve to the stomach are cut in order to reduce acid
secretion; and antrectomies, which involve the
removal of a part of the stomach (the antrum).

Treatment
Medications
Most drugs that are currently given to treat ulcers
work either by lowering the rate of stomach acid secretion or by protecting the mucous tissues that line the
digestive tract.
ANTISECRETORY DRUGS. Medications that lower
the rate of stomach acid secretions fall into two major
categories: proton pump inhibitors, which bind an
enzyme that secretes stomach acid, and H2 receptor
antagonists, which work by reducing intracellular acid
secretion. The proton pump inhibitors include omeprazole (Prilosec) and lansoprazole (Prevacid). The H2
receptor antagonists include ranitidine (Zantac), cimetidine (Tagamet), famotidine (Pepcid), and nizatidine
(Axid). Both types of drugs have few serious side effects
and appear to be safe for long-term use.
PROTECTIVE DRUGS. The drugs that are currently
used to protect the stomach tissues are sucralfate
(Carafate), which forms a pastelike substance that
clings to the mucous tissues and prevents further
damage from stomach acid; and bismuth preparations. A third type of protective drug includes misoprostol (Cytotec), which is often given to patients with
ulcers caused by NSAIDs.

3838

Eradication of Helicobacter pylori
Most doctors presently recommend treatment to
eliminate H. pylori in order to prevent ulcer recurrences. Without such treatment, ulcers recur at the
rate of 80% per year. A 2003 report showed that
eradication H. pylori alone usually prevents recurring
bleeding ulcers. The usual regimen used to eliminate
the bacterium is a combination of tetracycline, bismuth subsalicylate (Pepto-Bismol), and metronidazole (Metizol).

Alternative treatment
Alternative treatments can relieve symptoms and
promote healing of ulcers. A primary goal of these
treatments is to rebalance the stomach’s hydrochloric
acid output and to enhance the mucosal lining of the
stomach.
Food allergies have been pointed to as a major
cause of peptic (stomach) ulcers. An elimination/challenge diet can help identify the allergenic food(s) and
continued elimination of these foods can assist in healing the ulcer. People with ulcers should not take
aspirin. They also should stop smoking, since smoking
irritates the mucosal lining of the stomach. Antacids
GALE ENCYCLOPEDIA OF MEDICINE

Botanical medicine offers a variety of remedies that may be helpful in ulcer treatment.
Deglycyrrhizinated licorice or DGL, in a chewable or
powder form, can help heal the mucous membranes
and increase mucous so that it mixes with saliva to
protect the membranes. Raw cabbage juice, high in
glutanic acid, is very effective in healing an ulcer (one
quart per day in divided doses). Soothing herbs, such
as plantain (Plantago major), marsh mallow (Althaea
officinalis), and slippery elm (Ulmus fulva); astringent
herbs, such as geranium (Pelargonium odoratissimum);
and the anitmicrobial herb goldenseal (Hydrastis
canadensis) can all be effective. Nutritionists advise
taking antioxidant nutrients, including vitamins A, C,
and E, zinc, and selenium.

Prognosis
The prognosis for recovery from ulcers is good for
most patients. Very few ulcers fail to respond to the
medications that are currently used to treat them.
Recurrences can be eliminated completely or cut to
5% by eradication of H. pylori. Most patients who
develop complications recover without problems
even when emergency surgery is necessary.

Prevention
Strategies for the prevention of ulcers or their
recurrence include the following:


eradication of H. pylori in patients already diagnosed
with ulcers



giving misoprostol to patients who must take
NSAIDs



avoiding unnecessary use of aspirin and NSAIDs



giving up smoking



cutting down on alcohol, tea, coffee, and sodas containing caffeine.

Resources
PERIODICALS

‘‘Many Peptic Ulcer Diagnoses Based on Symptoms Alone.’’
AORN Journal August 2003: 210.
Worcester, Sharon. ‘‘Eradicating H. Pylori May Prevent
Bleeding Ulcers: No [Histamine. Sub2] Blockers
Needed.’’ Internal Medicine News September 15, 2003: 33.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American College of Gastroenterology. 4900-B South
Thirty-First St., Arlington, VA 22206-1656. (703) 8207400. <http://www.acg.cgi.gi.org/acghome/html>.
Digestive Health Initiative. 7910 Woodmont Ave., #914,
Bethesda, MD 20814. (800) 668-5237. <http://
www.gastro.org./dhi.html>.

Rebecca J. Frey, PhD
Teresa G. Odle

Ultrasonic lithotripsy see Lithotripsy

Ultraviolet light treatment
Definition
Ultraviolet light treatment uses a particular band
of the nonvisible light spectrum to treat psoriasis and a
variety of other skin diseases. It can be used alone or in
combination with other medications applied directly
to the skin or taken internally.

Purpose
Ultraviolet (UV) light treatment is used primarily
in cases of severe psoriasis that have not responded to
other medications or in cases affecting large portions of
the body. Patients will typically receive a series of 3–5
weekly treatments for a month or more to bring their
psoriasis symptoms into check. They may also receive
periodic maintenance treatments to prevent recurrence
of their psoriasis. Other skin conditions treated with
UV light treatments are vitiligo, a condition in which
people lose pigmentation in large patches of their skin,
and atopic dermatitis, an allergy-related skin condition
that produces itchy, reddish, and scaly patches of skin.

Precautions
Exposure to UV radiation is known to prematurely age the skin over time and increase the risk of
skin cancer. These potential effects should be weighed
against the potential benefits of the treatment. A history will be taken regarding sun exposure and burning,
medications, such as diuretics, that may increase UV
sensitivity exposure, and any history of skin cancers.
Sometimes, UV light treatments are given in combination with photosensitizing agents, which maximize
UV’s effects on the skin. Patients who receive these
agents, called psoralens, must take care to avoid exposure to sunlight, which also contains UV radiation.
Exposure to UV radiation can also cause cataracts and
3839

Ultraviolet light treatment

should be avoided by anyone with an ulcer, because
they can cause a rebound effect of increasing gastric
acid secretion, as well as deplete vital nutrients necessary for healing. Stress reduction is also important for
ulcer sufferers.

Ultraviolet light treatment

other eye damage, so the patient’s eyes must be adequately shielded during the treatments.

Description
UV light treatment can employ one of two bands
of the ultraviolet spectrum: ultraviolet A (UVA), and
ultraviolet B (UVB). Patients receive full-body treatments in special light boxes; smaller areas of the skin
are sometimes treated with hand-held devices.
UVB treatment
Psoriasis is the most common skin disease treated
with UVB light treatment. Its mechanism of action
remains unclear, but investigators speculate it may
kill abnormal skin cells or alter immune system reactions in the skin. Most patients require 18–30 treatments before substantial improvement or complete
clearing is seen. The intensity of the UV applied will
vary depending on the patient’s skin type. Fairskinned patients will start with a relatively weaker
dose; dark-skinned patients, a stronger dose.
Physicians will first expose a small area of skin to
UVB to determine the minimum erythema dose
(MED), the minimum amount of UVB that produces
redness 24 hours after exposure. Patients will be
exposed for short times early in the treatment cycle,
but these times will gradually increase over time.
The Goeckerman regimen, a treatment that combines UVB light with coal tar applied to the skin, is
among the oldest and most frequently used treatments
for patients with moderate to severe psoriasis. The
coal tar is a photosensitizing agent, and, when it interacts with UVB, it appears to limit the abnormal turnover of skin cells characteristic of psoriasis. Although
treatments with UVB and coal tar are highly effective,
many patients dislike the smell. Some investigators
believe that the use of petroleum jelly or other emollients is just as effective as the coal tar preparations.
In addition to their UVB treatments, many
patients will receive such systemic agents as methotrexate, a drug used in severe case of psoriasis, and
certain vitamin A derivatives called retinoids. A newer
retinoid called bexarotene (Targretin), which was originally developed to treat cutaneous T-cell lymphoma,
shows promise as a treatment for psoriasis in combination with UVB therapy.
Another new development in UV therapy is the
use of a laser as the source of the UVB radiation. The
type of laser that is used is known as a 308-nm excimer
laser, which uses a specific mixture of gases to produce
high-intensity, short pulses of UV light.
3840

PUVA treatment
Psoralens are photosensitizing agents found in
plants. They have been known since ancient Egypt but
have only been available in a chemically synthesized
form since the 1970s. Psoralens are taken systemically
or can be applied directly to the skin. The psoralens
allow a relatively lower dose of UVA to be used. When
they are combined with exposure to UVA in PUVA,
they are highly effective at clearing psoriasis. Like UVB
light treatments, the reason remains unclear, though
investigators speculate there may be similar effects on
cell turnover and the skin’s immune response.
Choosing the proper dose for PUVA is similar to
the procedure followed with UVB. The physician can
choose a dose based on the patient’s skin type. Often,
however, a small area of the patient’s skin will be
exposed to UVA after ingestion of a psoralen. The
dose of UVA that produces uniform redness 72
hours later, called the minimum phototoxic dose
(MPD), becomes the starting dose for treatment.
Some patients experience nausea and itching after
ingesting the psoralen compound. For these patients
‘‘bath PUVA’’ may be a good option.

Preparation
No major preparation is required for UV light
treatments. Areas of the skin that are especially sensitive to the effects of UV light, such as the groin, backside, or face, are shielded during the treatments. Areas
not affected by psoriasis are also covered. Special
goggles are worn to protect the eyes. Some physicians
apply an emollient, such as petroleum jelly, to the skin
or other topical agents, such as coal tar, to enhance the
results. In PUVA treatments, the psoralen is usually
taken one hour before the treatment.

Aftercare
No major aftercare is required following UV light
treatments. Patients, however, must take great care to
limit or eliminate other exposures to UV radiation,
such as from sunlight or tanning beds, because of the
increased risk of premature aging of the skin and the
development of skin cancers. Patients should monitor
their skin closely for any signs of precancerous or
cancerous skin growths in the future.

Risks
People who receive UV light treatments are at
higher risk of premature aging of the skin, and of developing skin cancer. These risks should be balanced
GALE ENCYCLOPEDIA OF MEDICINE

Erythema—The medical term for redness of the
skin produced by congestion of the capillaries in
the skin.
Goeckerman regimen—UVB light therapy combined with topical coal-tar preparations.
Minimum erythema dose—The minimum amount
of UVB that produces redness 24 hours after exposure. It is the starting dose for UVB light treatments.
Minimum phototoxic dose— The dose of UVA that
produces uniform redness 72 hours after ingesting a
psoralen compound. It becomes the starting dose
for PUVA treatment.
Psoralen—A family of photosensitizing chemicals
that can be found in lemons, celery, and other
plants. Chemically synthesized versions are used
to augment the effects of UVA light treatments.
PUVA treatments—Treatments with the photosensitizers called psoralens and UVA.
Ultraviolet light—A portion of the light spectrum
not visible to the eye. Two bands of the UV spectrum, UVA and UVB, are used to treat psoriasis and
other skin diseases.

against the benefits of treatment. Patients must also take
care to limit or eliminate their exposure to other sources
of UV radiation, especially if they are taking a psoralen
compound in addition to receiving the UV treatments.

Normal results

an extreme reaction to UV radiation. One medication
that has been shown to be helpful in treating burns
caused by overexposure to UV radiation is a gel
containing a platelet-activating antagonist factor, or
PAF, known as WEB 2086.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Psoriasis.’’ Section 10, Chapter 117 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PERIODICALS

Baltas, E., V. Trach, A. Dobozy, and L. Kemeny. ‘‘PlateletActivating Factor Antagonist WEB 2086 Inhibits
Ultraviolet-B Radiation-Induced Dermatitis in the
Human Skin.’’ Skin Pharmacology and Applied Skin
Physiology 16 (July-August 2003): 259–262.
Bianchi, B., P. Capolmi, L. Mavilia, et al. ‘‘Monochromatic
Excimer Light (308 nm): An Immunohistochemical
Study of Cutaneous T Cells and Apoptosis-Related
Molecules in Psoriasis.’’ Journal of the European
Academy of Dermatology and Venereology 17 (July
2003): 408–413.
Smit, J. V., E. M. De Jong, and P. C. Van De Kerkhof.
‘‘Effects of Oral Bexarotene (Targretin) on the Minimal
Erythema Dose for Broad-Spectrum UVB Light.’’ Skin
Pharmacology and Applied Skin Physiology 16 (JulyAugust 2003): 237–241.
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. <http://www.aad.org>.
National Psoriasis Foundation. 6600 SW 92nd Ave., Suite
300, Portland OR 97223-7195. (503) 244-7404. <http://
www.psoriasis.org>.

Psoriasis will normally show significant improvement to complete healing with three to five UVB treatments a week for about four to five weeks. PUVA
treatments may require a bit longer to take effect,
but because the overall dosage of UV is lower, they
are thought by some investigators to be a safer alternative to UVB treatments.

Richard H. Camer
Rebecca J. Frey, PhD

Umbilical cord blood banking
Abnormal results
Modern light boxes carefully control the dosage
of UV radiation and the exposure time. Overdose
or overexposure is possible, however, and can lead
to severe burns. It is important to choose a treatment
provider who is experienced in the technique. It is also
important to tell the physician about all medications
being taken by the patient. Some medications, either
alone or in combination with a psoralen, can provoke
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Umbilical cord blood banking is the practice of
preserving for future use fetal blood that remains in
the umbilical cord at the time of birth.

Purpose
During pregnancy, a developing fetus is attached
to its mother’s placenta by the umbilical cord. At
3841

Umbilical cord blood banking

KEY TERMS

Umbilical cord blood banking

birth, this cord is cut, and the placenta is expelled from
the mother. Some fetal blood remains in the umbilical
cord. Normally, this blood, along with the cord and
the placenta, are simply disposed of. However, now
there are ways to freeze the cord blood for future use.
Umbilical cord blood is special because it contains
a lot of cells called hematopoietic stem cells. A stem
cell is an unspecialized master cell that can develop
into several different kinds of specialized cells.
Hematopoietic stem cells normally develop into red
blood cells that carry oxygen, white blood cells that
fight infection, and platelets that help make blood clot.
These hematopoietic stem cells are not the same as
embryonic stem cells that are at the center political
and ethical debate about their use in research. Their
collection does not harm either the mother or the
baby.
There are two other sources of hematopoietic
stem cells—bone marrow and peripheral blood. Bone
marrow is the spongy material inside bones that is the
source for new blood cells produced throughout an
individual’s life. Peripheral blood is the blood that
circulates through the body.
All cells have a protein profile that identifies them.
When a foreign cell enters the body, immune system
cells recognize the protein profile as foreign and attack
the cell. The advantage of umbilical cord stem cells
that they are more immature and have a less well
developed protein profile than bone marrow or peripheral stem cells. As a result, they draw a weaker
response from the body’s immune system.
The protein profile of human cells is called the
human leukocyte antigen (HLA) profile. Normally
for transplanted cells such as bone marrow cells to be
accepted, there must be a close to perfect match
between the HLA profile of the donor and the recipient. Since there are over 10,000 HLA types, finding an
exact match can be difficult. Because umbilical cord
blood cells have a less well developed HLA profile,
they do not have to match the recipient’s HLA as
closely to be accepted by the immune system of the
transplant recipient.
Types of cord blood banks
There are two types of umbilical cord blood
banks—private and public. Private blood cord banks
can be for-profit or not-for-profit. They sell kits that
can be used at any delivery to collect cord blood. They
also charge a yearly fee to store the blood. The cord
blood is available only to the child or members of the
child’s family from which it came. It is a perfect HLA
match to child’s blood. When a transplant is done
3842

using cells that came from the individual who needs
the transplant, it is called an autologous transplant.
Autologous transplants have a high rate of success.
Public cord banks do not charge a fee to collect or
store cord blood. Parents of newborns donate the cord
blood, and it is then available to anyone who needs it
and is an appropriate match. This type of transplant
where the recipient is not the same as the donor is
called an allogeneic transplant. Much of the success
of allogeneic transplants depends on finding a good
HLA match. Because of funding considerations, there
are a limited number of public cord blood banks. To
donate to a public blood cord bank, the mother must
give birth in a facility associated with a public blood
cord bank.
How cord blood is used
The first successful umbilical cord stem cell transplantation occurred in 1988, when a newborn girl
donated cord blood to cure her brother of Fanconi’s
anemia, a genetic defect. Many other blood diseases
can now be treated successfully with cord stem cell
transplants. These same diseases can be treated with
bone marrow transplant if an appropriately matched
donor can be found. In addition, research is ongoing
in the hope that cord blood stem cells can be induced
into differentiating into other types of cells, such as
nerve cells that can be used to treat other diseases.
Some diseases treated with blood stem cell transplant include:


acute lymphatic leukemia



acute myelogenous leukemia



chronic myelogenous leukemia



Hodgkin disease



Non-Hodgkin lymphoma



neuroblastoma



severe combined immune deficiency



anapalstic anemia



thalassemia



sickle cell anemia



Fanconi’s anemia

In addition to being more readily accepted by the
donor’s body, cord blood offers other advantages over
bone marrow transplantation. It is relatively quick and
easy to thaw the cord blood and infuse it, while bone
marrow harvesting is an invasive procedure with
risks to the donor. In addition, cord blood is less likely
to be contaminated with viruses that may create complications for the recipient.
GALE ENCYCLOPEDIA OF MEDICINE

Although the list of diseases treated with umbilical cord stem cells is impressive and growing, controversy exists about whether parents should pay
private cord cell banks to preserve their newborn’s
blood. Private cord cell banks sell their services as
a type of ‘‘insurance.’’ In case the child develops
a treatable disease, the child’s own stem cells will
be a perfect match. However, if the disease is caused
by a genetic defect, (e.g., sickle cell and other anemias) the child’s own stem cells will be useless,
because they will contain the same genetic defect.
In addition, the quantity of cord blood that can be
collected is only enough to treat a child. Although
research is being done to try to multiply cord cells in
the laboratory in quantities great enough to treat an
adult, results have not been successful. Therefore,
if an adult develops a treatable disease, even if his
own cord blood was banked, the quantity will be
insufficient to produce a cure. Also, cord blood
storage is a new enough technology, that it is not
clear how long the blood can remain frozen and still
be effective.
In the most recent statement on cord blood banking released by the American Academy of Pediatrics in
1999, they concluded:


There are no good estimates of how often a child will
need a transplant of his own cells. Estimates range
from 1 in 1,000 to 1 in 200,000



Certain genetic disorders are not cured by autologous transplants



Parents should be encouraged to donate their child’s
cord blood to free public cord blood banks for the
widest possible use rather than paying private companies to store cord blood

The American College of Obstetricians and
Gynecologists supports the position that parents
should not be sold private blood cord banking without
a realistic assessment of their need, nor should parents
feel guilty if they are not eager or able to meet the
annual expense associated with private storage.
Although cord blood collection is safe, unless there is
a family history of diseases for which hematopoietic
stem cells are helpful, most pediatricians and obstetricians feel private cord blood storage is an unnecessary
expense.

Precautions
Umbilical cord blood collection is usually not
done in the case of multiple births.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Allogeneic—A transplant where the donated material comes from different (although often related)
individual than the recipient
Autologous—A transplant where the material for
the transplant comes from the individual who is
also the recipient; thus, the transplant material is
genetically identical to the donor’s body.
Hematopoietic stem cell—A cell that can develop
into any type of specialized blood cell.

Description
Cord blood collection is a simple procedure that
takes between three and seven minutes. It is done
immediately after the baby is delivered. Cord blood
is drained into a standard blood bag, and then processed and frozen at very low temperatures.

Preparation
Parents who wish to bank their child’s cord blood
must plan ahead. Private storage requires ordering a
kit in advance and coordinating with the health care
providers doing the delivery to make sure the cord
blood is collected properly. Mothers must test negative for infectious diseases such as HIV and hepatitis
before delivery. Donation to a public cord blood bank
is not always possible because of their limited number
and location.

Aftercare
No special aftercare is required for mother or
child, but the cord blood must remain frozen at low
temperatures.

Risks
The main risk associated with umbilical cord
blood collection is the possibility that it will become
contaminated with bacteria during collection.
Parents who are interested in private cord
blood storage should research the company with
which they contract, just as they would in making
any business decision. They need to know the costs,
whether the annual fee can increase, and what will
happen to the blood if the company goes out of
business.
3843

Umbilical cord blood banking

Considerations in deciding to bank cord blood

Undescended testes

Resources

KEY TERMS

PERIODICALS

Chao, Nelson J, Stephen G. Emerson, and Kenneth I.
Weinberg ‘‘Stem Cell Transplantation (Cord Blood
Transplantation)’’ Hematology 2004 no. 1 pp. 354-371.
[cited 1 March 2005].
Oh, Weltham et at. ‘‘Cord Blood Banking for Potential
Future Transplantation: Subject Review’’ Pediatrics 104
no. 1 (July 1999) pp. 116-118 [cited 16 February 2005].
ORGANIZATION

Leukemia and Lymphoma Society. 1311 Mamaroneck
Avenue, White Plains, New York 10605. 914-949-6691.
<http://www.LLS.org>.
OTHER

Coale, Kristi. ‘‘Can the Umbilical Cord Save Lives?’’
WebMD, 26 June 2000 [cited 16 February 2005].
<http://www.leukemia-lymphoma.org/
all_mat_toc.adp?item_id=9622gt;.
Eflom-Ekaha, Daniel and Arunbhai G. Patel. Hematopoietic
Stem Cell Transplantation, 13 October 2004 [cited 5
March 2005]. <http://www.emedicine.com/med/
topic3387.htm>.
‘‘Cord Blood Stem Cell Transplantation’’ Leukemia and
Lymphoma Society, [cited 1 March 2005]. <http://
my.webmd.com/content/Article/13/
1691_50298.htm>.
Moran, Mark. ‘‘Banking on Umbilical Cord Blood,’’
WebMD, 2001 [cited 16 February 2005]. <kidshealth.org/parent/pregnancy_newborn/pregnancy/
cord_blood.html>.
Nemours Foundation. ‘‘Banking Your Newborn’s Cord
Blood,’’ KidsHealth, June 2004 [cited 16 February
2005]. <http://my.webmd.com/content/Article/14/
3606_537.htm>.
‘‘Patient Fact Sheet on Umbilical Cord Blood
Transplantation’’ National Marrow Donor Program, 17
February 2005 [cited 1 March 2005]. <http://
www.marrow.org/PATIENT/patient_fact_sheet_
umbilical_cord_blood_transplantation.htm>.

Tish Davidson, A. M.

Uncinariasis see Hookworm disease

Undescended testes
Definition
Also known as cryptorchidism, undescended
testes is a congenital condition characterized by testicles that do not extend to the scrotum.
3844

Cryptorchidism—Undescended testes.
Embryonic—Early stages of life in the womb.
Fetal—Refers to the fetus, also known in the first
two months after conception as an embryo.
Orchiopexy—Surgical procedure that places the
testicles in the scrotum.

Description
In the fetus, the testes are in the abdomen. As
development progresses they migrate downward
through the groin and into the scrotum. This event
takes place late in fetal development, during the eighth
month of gestation. Thirty percent of premature boys
have testes that have not yet made the full descent.
Only 3–4% of full-term baby boys have undescended
testes, and half of those complete the journey by the
age of three months. Eighty percent of all undescended
testes cases naturally correct themselves during the
first year of life. Undescended testes that are not corrected can lead to sterility and an increased risk of
testicular cancer.

Causes and symptoms
The cause of undescended testes is presently
unknown, however its symptoms are quite apparent.
One or all of the testicles can be undescended, therefore the testicles appear to be either missing or
lopsided.

Diagnosis
The newborn examination always checks for
testes in the scrotum. It they are not found, a search
will be conducted, but not necessarily right away. In
most cases, the testes will drop into place later. If the
testes are present at all, they can be anywhere within a
couple inches of the appropriate spot. In 5% of cases,
one testis is completely absent. In 10%, the condition
occurs on both sides. Presence of undescended testes is
indicated by measuring the amount of gonadotropin
hormone in the blood.

Treatment
Once it is determined that the testes will not
naturally descend, surgery becomes necessary. The
procedure is called an orchiopexy and is relatively
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Undescended testes must be treated to eliminate
the increased risk of testicular cancer and the possibility of sterility. Undescended testes are twice as likely
to develop cancer. Ten percent of all testicular cancers
are in undescended testes.
Resources
BOOKS

Rajfer, Jacob. ‘‘Congenital Anomalies of the Testes and
Scrotum.’’ In Campbell’s Urology, edited by Patrick
C. Walsh, et al. Philadelphia: W. B. Saunders Co.,1998.

J. Ricker Polsdorfer, MD

Undulant fever see Brucellosis
Unipolar depression see Depressive
disorders

Upper GI exam
Definition
An upper GI examination is a fluoroscopic examination (a type of x-ray imaging) of the upper gastrointestinal tract, including the esophagus, stomach, and
upper small intestine (duodenum).

Purpose
An upper GI series is frequently requested when a
patient experiences unexplained symptoms of abdominal pain, difficulty in swallowing (dysphagia), regurgitation, diarrhea, or weight loss. It is used to help
diagnose disorders and diseases of, or related to, the
upper gastrointestinal tract, including cases of hiatal
hernia, diverticuli, ulcers, tumors, obstruction, enteritis, gastroesophageal reflux disease, Crohn’s disease,
and pulmonary aspiration.

Precautions
Because of the risks of radiation exposure to the
fetus, pregnant women are advised to avoid this procedure. Patients with an obstruction or perforation in
their bowel should not ingest barium (a radioactive
GALE ENCYCLOPEDIA OF MEDICINE

substance used to show contrast in the images) for an
upper GI, but may still be able to undergo the procedure if a water-soluble contrast medium is substituted
for the barium.
Glucagon, a medication sometimes given prior to
an upper GI procedure, may cause nausea and
dizziness.

Description
An upper GI series takes place in a hospital or
clinic setting and is performed by an x-ray technician
and a radiologist. A radiologist typically is in attendance to oversee the procedure, and view and interpret the fluoroscopic pictures. Before the test begins,
the patient is sometimes administered an injection of
glucagon, a medication which slows stomach and
bowel activity, to allow the radiologist to get a
clearer picture of the gastrointestinal tract. In order
to further improve the clarity of the upper GI pictures, the patient may be given a cup of baking soda
crystals to swallow, which distend the stomach by
producing gas.
Once these preparatory steps are complete, the
patient stands against an upright x-ray table, and a
fluoroscopic screen is placed in front of him. The
patient will be asked to drink from a cup of flavored
barium sulfate, a thick and chalky-tasting liquid that
allows the radiologist to see the digestive tract, while
the radiologist views the esophagus, stomach, and
duodenum on the fluoroscopic screen. The patient
will be asked to change positions frequently in order
to coat the entire surface of the gastrointestinal tract
with barium. The technician or radiologist may press
on the patient’s abdomen in order to spread the barium. The x-ray table will also be moved several times
throughout the procedure. The radiologist will ask the
patient to hold his breath periodically while exposures
are being taken. The entire procedure takes approximately 30 minutes.
In some cases, in addition to the standard upper
GI series, a doctor may request a detailed intestine, or
small bowel, radiography and fluoroscopy series; it is
also called a small bowel follow-through (SBFT).
Once the preliminary upper GI series is complete, the
patient will be escorted to a waiting area while the
barium travels down through the rest of the small
intestinal path. Every 15–30 minutes, the patient will
return to the x-ray suite for additional x rays, or films.
Once the barium has completed its trip down the small
bowel tract, the test is completed. This procedure can
take anywhere from one to four hours.
3845

Upper GI exam

simple once the testes are located. The surgery is
usually performed when the boy is between one to
two years old.

Ureteral stenting

Esophageal radiography, also called a barium
esophagram or a barium swallow, is a study of the
esophagus only, and is usually performed as part
of the upper GI series. It is commonly used to diagnose the cause of difficulty in swallowing (dysphagia) and for detecting hiatal hernia. A barium
sulfate liquid, and sometimes pieces of food covered
in barium, are given to the patient to drink and eat
while a radiologist examines the swallowing mechanism on a fluoroscopic screen. The test takes approximately 30 minutes.

Preparation
Patients must not eat, drink, or smoke for eight
hours prior to undergoing an upper GI examination.
Longer dietary restrictions may be required, depending on the type and diagnostic purpose of the test.
Patients undergoing a small bowel follow-through
exam may be asked to take laxatives the day prior to
the test. Upper GI patients are typically required to
wear a hospital gown, or similar attire, and to remove
all jewelry, so the camera has an unobstructed view of
the abdomen.

Aftercare
No special aftercare treatment or regimen is
required for an upper GI series. The patient may
eat and drink as soon as the test is completed. The
barium sulfate may make the patient’s stool white for
several days, and patients are encouraged to drink
plenty of fluids in order to eliminate it from their
system.

Risks
Because the upper GI series is an x-ray procedure,
it does involve minor exposure to ionizing radiation.
Unless the patient is pregnant, or multiple radiological
or fluoroscopic studies are required, the small dose of
radiation incurred during a single procedure poses
little risk. However, multiple studies requiring fluoroscopic exposure that are conducted in a short time
period have been known, on rare occasions, to cause
skin death (necrosis) in some individuals. This risk can
be minimized by careful monitoring and documentation of cumulative radiation doses administered to
these patients.

Normal results
A normal upper GI series will show a healthy,
functioning, and unobstructed digestive tract.
3846

Abnormal results
Obstructions or inflammation, including ulcers of
the esophagus, stomach, or small intestine; or irregularities in the swallowing mechanism are just a few of the
possible abnormalities that may show up on an upper
GI series.
Resources
PERIODICALS

Newman, J. ‘‘Radiographic and Endoscopic Evaluation of
the Upper GI Tract.’’ Radiology Technology 69, no. 3
(January-February 1998): 213-26.

Paula Anne Ford-Martin

Urea clearance by the kidneys see Kidney
function tests

Ureteral stenting
Definition
Ureteral stents are thin catheters threaded into
segments of the ureter that carry urine, produced by
the kidney, either down into the bladder internally, or
to an external collection system. Insertion is most
often done through the skin (percutaneously); however, in the presence of kidney or ureteral stones,
stenting is ideally done during cystoscopy.

Purpose
Ureteral stenting may be placed on a long-term
basis (months to years) in order to bypass ureteral
obstruction. Short-term stenting (weeks to months)
may be used as an adjunct to open surgical procedures
of the urinary tract to provide a mold around which
healing can occur, or to divert the urinary flow away
from areas of leakage. Following balloon dilation or
incision of ureteral strictures, placement of stents
maintains the functionality of the ureters. Stents may
also be used in the presence of kidney stones to manipulate or prevent stone migration prior to treatment, or
to make the ureters more easily identifiable during
difficult surgical procedures. Ureteral stents may be
used in those with active kidney infection or with
markedly diseased, intolerant bladders (e.g., damage
from radiation therapy, bladder invasion by adjacent
neoplasm).
GALE ENCYCLOPEDIA OF MEDICINE

Cystoscopy—Examination or treatment of the interior of the urinary bladder by looking through a
special instrument with reflected light.
Stricture—An abnormal narrowing of a tube or
passageway.
Ureter—The tube-like passageway in the body that
carries urine from the kidney to the bladder.

BOOKS

Schrier, Robert, and Carl Gottschalk. Diseases of the
Kidney. Philadelphia: Little, Brown and Co., 1997.

Kathleen D. Wright, RN

Ureterostomy see Urinary diversion surgery
Urethra defects see Hypospadias and
epispadias

Preparation
The procedure should be thoroughly explained by
a medical professional before it takes place. The
patient will be asked to put on a hospital gown. If
the procedure is performed with the aid of a cytoscope,
the patient will assume a position that is typically used
in a gynecological exam.

Aftercare
Stents must be periodically replaced to prevent
fractures within the catheter wall, or buildup of
encrustation. Stent replacement is recommended
approximately every six months or more often in
patients who form stones.

Normal results
Normally, a ureteral stent assures the patient of a
free flow of urine. Postoperatively, urine flow will be
monitored to ensure the stent has not been dislodged
or obstructed.

Abnormal results
Serious complications of the procedure occur in
approximately four percent of cases, with minor complications in another 10%. These may include:

Urethritis
Definition
Urethritis is an inflammation of the urethra that is
usually caused by an infection.

Description
The urethra is the canal that moves urine from the
bladder to the outside of the body. When this canal
becomes infected, inflammation occurs due to the
accumulation of white blood cells in the area. When
this occurs, it is called urethritis. Besides the urethra,
the urinary tract consists of the bladder, ureters, and
kidneys. Inflammation can move up the urethra, causing cystitis in the bladder, or nephritis in the kidneys.
Collectively, these inflammations are called urinary
tract infections or UTIs.
Urinary tract infections are much more common
in women than in men, probably due to anatomy.
Infections are especially more common in older
women, due to bladder problems.

Causes and symptoms



Bleeding. Usually minor and easily treated, occasionally requiring transfusion



Catheter migration or dislodgement. May require
readjustment with the fluoroscope in the Radiology
Department



Coiling of the stent within the ureter. May cause
lower abdominal pain or flank pain on urination,
urinary frequency, or blood in the urine



Introduction or worsening of infection

Uncomplicated urethritis usually results from
infection by the bacteria Escherichia coli, commonly
found in the bowel. Complicated urethritis can occur
when other problems exist, such as kidney stones, malformations of the urinary tract, spinal cord injury, or a
compromised immune system. People with diabetes
tend to have more urinary tract infections, as well as
hospitalized patients. Urinary tract infections can also
be sexually transmitted. Some people seem to be susceptible to urinary tract infections, having them
recurrently.



Penetration of adjacent organs (e.g., bowel, gallbladder, or lungs)

Frequently, a urinary tract infection has no symptoms. Common symptoms though, include pain and a

GALE ENCYCLOPEDIA OF MEDICINE

3847

Urethritis

Resources

KEY TERMS

Urethritis

system. Adding a teaspoon of baking soda to a glass
of water and drinking it can change the pH of the
urine, causing it to burn less. Also, cranberry juice
contains a compound that can prevent bacteria from
sticking to and thus growing in the urinary tract.
Antimicrobial herbs, such as uva ursi (Arctostaphylos
uva-ursi) and pipsissewa (Chimaphila umbellata), may
be helpful. Other herbs, such as marsh mallow
(Althaea officinalis), slippery elm (Ulmus fulva), comfrey (Symphytum officinale), plantain (Plantago
major), and cornsilk, can soothe the urinary tract.
Lactobacillus acidophilus and L. bifidus supplementation reintroduces normal flora into the urinary tract.
Acupuncture and homeopathy can also be effective
therapies for urethritis.

Prognosis

A false color transmission electron micrograph (TEM) scan of
non-specific urethritis. (Photograph by Dr. R. Dourmashkin,
Custom Medical Stock Photo. Reproduced by permission.)

burning sensation when urinating, frequent urination,
or passing blood in the urine. Signs that the infection
may be worsening include fever and chills, nausea,
vomiting, and lower back pain.

Given the appropriate antibiotic, urinary tract
infections usually go away quickly. If not treated
soon enough, however, urethritis can move up the
urinary tract, infecting the bladder and possibly the
kidneys, resulting in kidney damage. If the infection
moves into the blood, additional complications can
arise. Those who have previously had a urinary tract
infection are more susceptible to additional urinary
tract infections. Because of this, patients need to be
aware of the symptoms so that a physician can be
notified if the infection becomes recurrent.

Prevention

Diagnosis
The diagnosis for a urinary tract infection is made
by assessing the symptoms, feeling (palpating) the
abdomen for tenderness, and a urinalysis. A urinalysis,
or urine sample, is examined for both the presence of
bacteria and white blood cells. After this, a urine culture to determine what bacteria is causing the infection
may be done.

Treatment
Typical treatment for urinary tract infections is a
course of antibiotics. In women who have recurrent
urethritis, the diagnosis and treatment is often
resolved over the phone. Additional drugs are sometimes given to relieve discomfort.

Alternative treatment
For those individuals who seem to be more susceptible to urinary tract infections, drinking lots of
fluids at the first sign of an infection can ward it off
by diluting the bacteria present and flushing the
3848

There are some steps that can be taken to keep the
urinary tract healthy and prevent infection.


drink plenty of fluids



do not hold urine once the urge to urinate has
occurred



after a bowel movement, wipe from front to rear to
keep bowel bacteria at a distance



wear cotton underwear



rinse soap off well in the shower



urinate after sexual intercourse



for post-menopausal women, estrogen replacement
therapy can help prevent urinary tract infection

Resources
PERIODICALS

‘‘Drink Away Urinary Tract Infections.’’ Prevention
Magazine January 1998: 135.

Cindy L. A. Jones, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Uric acid tests are tests that are done to measure
the levels of uric acid in blood serum or in urine.

Purpose
The uric acid tests are used to evaluate the blood
levels of uric acid for gout and to assess uric acid levels
in the urine for kidney stone formation. The urine test
is used most often to monitor patients already diagnosed with kidney stones, but it can also be used to
detect disorders that affect the body’s production of
uric acid and to help measure the level of kidney
functioning.
Uric acid is a waste product that results from the
breakdown of purine, a nucleic acid. (Nucleic acids are
the building blocks of DNA.) Uric acid is made in the
liver and excreted by the kidneys. If the liver produces
too much uric acid or the kidneys excrete too little, the
patient will have too much uric acid in the blood. This
condition is called hyperuricemia. Supersaturated uric
acid in the urine (uricosuria) can crystallize to form
kidney stones that may block the tubes that lead from
the kidneys to the bladder (the ureters).

Precautions

The laboratory should also be notified if the
patient has had recent x-ray tests requiring contrast
dyes. These chemicals increase uric acid levels in urine
and decrease them in blood.

Description
The uric acid blood test is performed on a sample
of the patient’s blood, withdrawn from a vein into a
vacuum tube. The procedure, which is called a venipuncture, takes about five minutes. The urine test
requires the patient to collect all urine voided over a
24-hour period, with the exception of the very first
specimen. The patient keeps the specimen container
on ice or in the refrigerator during the collection
period.

Preparation
The uric acid test requires either a blood or
urine sample. For the blood sample, the patient
should be fasting (nothing to eat or drink) for at
least eight hours before the test. The urine test for
uric acid requires a 24-hour urine collection. The
urine test does not require the patient to fast or
cut down on fluids. Some laboratories encourage
patients to drink plenty of fluids during the collection period.

Blood test
Patients scheduled for a blood test for uric acid
should be checked for the following medications: loop
diuretics (Diamox, Bumex, Edecrin, or Lasix); ethambutol (Myambutol); vincristine (Oncovin); pyrazinamide (Tebrazid); thiazide diuretics (Naturetin,
Hydrex, Diuril, Esidrix, HydroDiuril, Aquatensen,
Renese, Diurese); aspirin (low doses); acetaminophen
(Tylenol); ascorbic acid (vitamin C preparations);
levodopa (Larodopa); or phenacetin. These drugs
can affect test results.
Certain foods that are high in purine may increase
the patient’s levels of uric acid. These include kidneys,
liver, sweetbreads, sardines, anchovies, and meat
extracts.
Urine test
Patients should be checked for the following medications before the urine test: diuretics, aspirin, pyrazinamide (Tebrazid), phenylbutazone, probenecid
(Benemid), and allopurinol (Lopurin). If the patient
GALE ENCYCLOPEDIA OF MEDICINE

Risks
Risks for the blood test are minimal, but may
include slight bleeding from the puncture site, a small
bruise or swelling in the area, or fainting or feeling
lightheaded.

Normal results
Blood test
Reference values for blood uric acid vary from
laboratory to laboratory but are generally found
within the following range: Male: 2.1–8.5 mg/dL;
female: 2.0–6.6 mg/dL. Values may be slightly higher
in the elderly.
Urine test
Reference values for 24-hour urinary uric acid
vary from laboratory to laboratory but are generally
found within the following range: 250–750 mg/24
hours.
3849

Uric acid tests

Uric acid tests

needs to continue taking these medications, the laboratory should be notified.

Urinalysis

KEY TERMS

Urinalysis

Fanconi’s syndrome—A rare disorder caused by
vitamin D deficiency or exposure to heavy metals.
Gout—A metabolic disorder characterized by sudden recurring attacks of arthritis caused by deposits
of crystals that build up in the joints due to abnormally high uric acid blood levels. In gout, uric acid
may be overproduced, underexcreted, or both.
Hyperuricemia—Excessively high levels of uric
acid in the blood, often producing gout.
Purine—A white crystalline substance that is one of
the building blocks of DNA. Uric acid is produced
when purine is broken down in the body.
Uric acid—A compound resulting from the body’s
breakdown of purine. It is normally present in
human urine only in small amounts.
Uricosuria—Increased levels of uric acid in the urine.
Wilson’s disease—A rare hereditary disease
marked by the buildup of copper in the liver and
brain, causing loss of kidney function.

Abnormal results

Definition
Urinalysis is a diagnostic physical, chemical, and
microscopic examination of a urine sample (specimen). Specimens can be obtained by normal emptying
of the bladder (voiding) or by a hospital procedure
called catheterization.

Purpose
Urinalyses are performed for several reasons:


general evaluation of health



diagnosis of metabolic or systemic diseases that
affect kidney function



diagnosis of endocrine disorders. Twenty-four hour
urine studies are often ordered for these tests



diagnosis of diseases or disorders of the kidneys or
urinary tract



monitoring of patients with diabetes



testing for pregnancy



screening for drug abuse

The critical value for the blood test is a level of
uric acid higher than 12 milligrams per deciliter (about
3.4 ounces).
Increased production of uric acid may result from
eating foods that are high in purine. Increased uric
acid levels due to overproduction may also be caused
by gout, by a genetic disorder of purine metabolism, or
by metastatic cancer, destruction of red blood cells,
leukemia, or cancer chemotherapy.
Decreased excretion of uric acid is seen in chronic
kidney disease, low thyroid, toxemia of pregnancy, and
alcoholism. Patients with gout excrete less than half the
uric acid in their blood as other persons. Only 10-15%
of the total cases of hyperuricemia, however, are
caused by gout.
Abnormally low uric acid levels may indicate that
the patient is taking allopurinol or probenecid for
treatment of gout; may be pregnant; or suffers from
Wilson’s disease or Fanconi’s syndrome.
Resources

Precautions
Voided specimens
Urinalysis should not be performed while a
woman is menstruating or having a vaginal discharge.
A woman who must have a urinalysis while she has a
vaginal discharge or is having her period should insert
a fresh tampon before beginning the test. She should
also hold a piece of clean material over the entrance to
her vagina to avoid contaminating the specimen.
Patients do not have to fast or change their food
intake before a urine test. They should, however,
avoid intense athletic training or heavy physical
work before the test because it may result in small
amounts of blood in the urine.
The following drugs can affect urinalysis results.
The patient may be asked to stop taking them until
after the test:


nitrofurantoin
(Macrodantin,
Furadantin).
Nitrofurantoin is prescribed for infections of the
urinary tract and other bacterial infections



phenazopyridine (Pyridium). This medication is used
to relieve burning and pain caused by urinary-tract
infections

BOOKS

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.

Janis O. Flores
3850

GALE ENCYCLOPEDIA OF MEDICINE

rifampin (Rifadin). This medication is prescribed to
treat tuberculosis, prevent the spread of meningitis,
and treat other infections
Bladder catheterization

Bladder catheterization is sometimes used to collect urine samples from hospitalized patients. It should
not, however, be used to collect specimens from males
with acute inflammation of the prostate or from a
patient of either sex with a fractured pelvis.

Description
Collecting a urine sample from emptying the bladder takes about two or three minutes. The sample can
be collected at home as well as in a doctor’s office.
Urine specimens are usually collected early in the
morning before breakfast. Urine collected eight
hours after eating and at least six hours after the
most recent urination is more likely to indicate
abnormalities. Some people may be asked to void
into a clean container before getting out of bed in the
morning.
Specimen containers
The doctor or hospital will supply a sterile container for a specimen being collected for a colony
count. A colony count is a test that detects bacteria
in urine that has been cultured for 24–48 hours. It is
used instead of a routine urinalysis when a patient’s
symptoms suggest a urinary tract infection. Nonsterile
containers can be used for routine specimens that will
not be tested immediately after being collected. An
ordinary open-necked jar may be used after it and its
lid have been soaked in very hot water for 15–20
minutes and then air-dried.
Laboratory procedures
STORAGE. Urine specimens should not remain
unrefrigerated for longer than two hours. A urine
specimen that cannot be delivered to a laboratory
within two hours should be stored in a refrigerator.
The reason for this precaution is that urine samples
undergo chemical changes at room temperature.
Blood cells begin to dissolve and the urine loses its
acidity.
VISUAL EXAMINATION. A doctor, nurse, or laboratory technician will look at the specimen to see if the
urine is red, cloudy, or looks unusual in any way. He
or she will also note any unusual odor.
TESTING TECHNIQUES. Urine samples are tested
with a variety of different instruments and techniques.

GALE ENCYCLOPEDIA OF MEDICINE

Some tests use dipsticks, which are thin strips of plastic
that change color in the presence of specific substances.
Dipsticks can be used to measure the acidity of the urine
(its pH) or the presence of blood, protein, sugar, or
substances produced during the breakdown of fatty
acids (ketones). A urinometer is used to compare the
density of the urine specimen with the density of plain
water. This measurement is called specific gravity.
The urine specimen is also examined under a
microscope to determine whether it contains blood
cells, crystals, or small pieces of fibrous material
(casts).

Preparation
Voided specimens
Most urine specimens from adults or older children are collected by the patient’s voiding into a suitable container. Soaps and disinfectants may
contaminate urine specimens and should not be used.
The doctor or laboratory may supply a special antiseptic solution that won’t irritate the skin. The method
for collection varies somewhat according to age and
sex.
WOMEN AND GIRLS. Before collecting a urine sample, a woman or girl should use a clean cotton ball
moistened with lukewarm water to cleanse the external
genital area. Gently separating the folded skin (labia)
on either side of her vagina, she should move the
cotton ball from the front of the area to the back.
After repeating this process several times, using a
fresh piece of cotton each time, she should dry the
area with a clean towel.

To prevent menstrual blood, vaginal discharge, or
germs from the external genitalia from contaminating
the specimen, a woman or girl should release some
urine before she begins to collect her sample. A urine
specimen obtained this way is called a midstream clean
catch.
MEN AND BOYS. A man or boy should use a piece
of clean cotton, moistened with antiseptic, to cleanse
the head of his penis and the passage through which
urine leaves his body (the urethral meatus). He should
draw back his foreskin if he has not been circumcised.
He should move the cotton in a circular motion
away from the urinary opening, using a fresh piece of
cotton each time. After repeating this process several
times, he should use a fresh piece of cotton to remove
the antiseptic. After the area has been thoroughly
cleansed, he should begin urinating and collect a
small sample in a container without interrupting the
stream of urine.

3851

Urinalysis



Urinalysis

INFANTS. A parent, nurse, or doctor should
cleanse the child’s genitals and as much of the surrounding area as will fit into the sterile urine-collection
bag provided by the hospital. When the area has been
thoroughly cleansed, the bag should be attached to the
child’s genital area and left in place until the child has
urinated. It is important to remember not to touch the
inside of the bag and to remove it as soon as a specimen has been obtained.

Bladder catheterization
Bladder catheterization is a hospital procedure
used to collect uncontaminated urine when the patient
cannot void. A catheter is a thin flexible tube that the
doctor inserts through the urethra into the bladder to
allow urine to flow out. To minimize the risk of infecting the patient’s bladder with bacteria, many doctors
use a so-called Robinson catheter, which is a plain
rubber or latex tube that is removed as soon as the
specimen is collected.
Suprapubic bladder aspiration is a technique that
is sometimes used to collect urine from infants
younger than six months. The doctor withdraws
urine from the bladder into a syringe through a needle
inserted through the skin over the bladder. This technique is used only when the child cannot void because
of an abnormal urethra or if he or she has a urinary
tract infection that has not responded to treatment.

Aftercare
The patient may return to normal activities after
collecting the sample and may start taking medications that were discontinued before the test.

Risks
There are no risks associated with voided specimens. The risk of bladder infection from catheterization with a Robinson catheter is about 3%.

Normal results
Contents and appearance
Normal urine is a clear straw-colored liquid. It has
a slight odor. It contains some crystals, a small number of cells from the tissues that line the bladder, and
transparent (hyaline) casts. Normal urine does not
contain sugars, yeast cells, protein, ketones, bacteria,
or parasitic organisms.
The time of day a urine sample is collected can
make a difference in the appearance of the specimen.
3852

Some foods and medicines, including red beets, asparagus, and penicillin, can affect the color or smell of
urine. Although most color variations are harmless,
they sometimes indicate the presence of serious disease. A doctor, nurse, or laboratory technician should
be notified if the urine is red or cloudy or looks unusual in any way.
Acidity
The pH of normal urine is 4.5–8.0. Its specific
gravity is 1.0005–1.035.

Abnormal results
Cloudiness
Urine may be cloudy (turbid) because it contains
red or white blood cells, bacteria, fat, mucus, digestive
fluid (chyle), or pus from a bladder or kidney
infection.
Odor
Foul-smelling urine is a common symptom of
urinary-tract infection. A fruity odor is associated
with diabetes mellitus, starvation and dehydration, or
ketone formation. Other distinctive odors are present
in the urine of patients with maple syrup urine disease
or phenylketonuria (PKU).
Specific gravity
The specific gravity of urine can be affected by a
range of diseases and disorders. Low specific gravity
(below 1.005) is associated with diabetes insipidus,
nephrogenic diabetes insipidus, acute tubular necrosis,
and inflammation of the upper urinary tract (pyelonephritis). In fixed specific gravity, the specific gravity of
the urine remains at 1.010 no matter how much fluid
the person drinks. This condition occurs in patients
who have chronic inflammation of the small blood
vessels in the kidneys (glomerulonephritis) and serious
kidney damage. High specific gravity (above 1.035)
occurs in patients who are in shock or who suffer
from nephrotic syndrome, dehydration, acute glomerulonephritis, congestive heart failure, or liver failure.
pH
A pH factor greater than 7 (more alkaline) may
result from Fanconi’s syndrome, urinary tract infections, or metabolic or respiratory alkalosis. A pH
factor below 7 (more acid) may be due to fever,
PKU, the secretion of homogentisic acid in the urine
(alkaptonuria), and acidosis.
GALE ENCYCLOPEDIA OF MEDICINE

Red blood cells in the urine can be due to vigorous
exercise or exposure to toxic chemicals. Bloody urine
can also be a sign of bleeding in the genitourinary tract
as a result of systemic bleeding disorders, various
kidney diseases, bacterial infections, parasitic infections including malaria, obstructions in the urinary
tract, scurvy, subacute bacterial endocarditis, traumatic injuries, and tumors.
A high number of white blood cells in the urine is
usually a symptom of urinary tract infection. A large
number of cells from tissue lining (epithelial cells) can
indicate damage to the small tubes that carry material
into and out of the kidneys.
Casts
Casts are small fibrous objects that are formed
when protein and other materials settle in the kidney
tubules and collecting ducts. Casts are dislodged by
normal urine flow. A large number of them in a urine
specimen is a sign of kidney disease.
Crystals
There are several different chemicals in body fluids
that can form crystals that appear in urine. Some of
these appear in normal urine, such as calcium oxalate or
uric acid crystals. A large number of calcium oxalate
crystals, however, may be a sign of abnormally high
levels of calcium in the blood (hypercalcemia). Other
crystals, including tyrosine, leucine, and cholesterol,
are abnormal. The presence of cystine crystals is a
symptom of excessive urinary secretion of cystine
(cystinuria). Cystine is an acid found in many proteins
and normally reabsorbed by the kidney tubules.
Protein
Protein in the urine can be a symptom of kidney
stones, inflammation of the kidneys, degenerative kidney disease, or multiple tumors.
Sugars
A high level of glucose and other sugars in the
urine (glycosuria) is often a symptom of diabetes mellitus. Glycosuria can also be caused by advanced kidney disease, Cushing’s syndrome, impaired tubular
reabsorption, shock, a rare tumor of the adrenal
gland (pheochromocytoma), or cancer of the pancreas.
Milk in the urine is normal if a woman is pregnant,
has just given birth, or is breastfeeding. On the other
hand, rare hereditary metabolic disorders are indicated
when urine contains fruit sugar (fructose), milk sugar
(galactose), or a simple sugar called pentose.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Acidosis—A condition of the blood in which bicarbonate levels are below normal.
Alkalosis—A condition of the blood and other body
fluids in which bicarbonate levels are higher than
normal.
Casts—Small fibrous objects formed from materials
that collect in the kidney tubules and are washed
out by normal urine flow.
Catheter—A thin flexible tube inserted through the
urethra into the bladder to allow urine to flow out.
Clean catch specimen—A urine specimen that is
collected from the middle of the urine stream after
the first part of the flow has been voided.
Colony count—A measurement of the growth of
bacteria in a urine sample that has been cultured
for 24 to 48 hours.
Fanconi’s syndrome—A rare disorder caused by
vitamin D deficiency or exposure to heavy metals.
Ketones—Substances produced during the breakdown of fatty acids. They are produced in excessive
amounts in diabetes and certain other abnormal
conditions.
Nephrotic syndrome—A condition characterized
by water retention, little or no protein in urine,
and high blood cholesterol.
pH—A chemical symbol used to describe the acidity or alkalinity of a fluid, ranging from 0 (more
acid) to 14 (more alkaline).
Urethra—The duct that carries urine from the bladder to the outside of the body.
Urinalysis (plural, urinalyses)—The diagnostic
testing of a urine sample.
Voiding—Another word for emptying the bladder
or urinating.

Ketones
The presence of abnormally high numbers of
ketones in the urine (ketonuria) usually results from
uncontrolled diabetes mellitus. Ketonuria can also be
caused by prolonged diarrhea or vomiting that results
in starvation.
Bilirubin
Bilirubin is an orange-yellow pigment found in
bile, a fluid secreted by the liver. When it is found in
urine, bilirubin may be a symptom of liver disease
3853

Urinalysis

Blood and tissue cells

Urinary anti-infectives

caused by the formation of fibrous tissue, medications
that damage the liver, or obstructive jaundice.
Urobilinogen
Bacteria in the small intestine can convert bilirubin to urobilinogen, which is excreted in the feces, in
bile, or in urine. An accumulation of urobilinogen in
the urine may be a sign of severe infection, liver
damage, or diseases that destroy red blood cells. Low
levels of urobilinogen in the urine may be a result of
antimicrobial therapy, inflammatory diseases, kidney
disease, severe diarrhea, or blocked bile ducts.

become infected when disease-causing organisms invade
from other body regions or from outside the body.
Urinary anti-infectives are used to treat such infections
or to prevent them in people who get them often.

Description
Commonly used urinary anti-infectives include
methenamine (Urex, Hiprex, Mandelamine), nalidixic
acid (NegGram) and nitrofurantoin (Macrobid,
Furatoin, and other brands). These medicines are
available only with a physician’s prescription and
come in capsule, tablet, granule, and liquid forms.

Recommended dosage

Other findings
The presence of bacteria, parasites, or yeast cells
in the urine may be a symptom of urinary tract infection or contamination of the external genitalia. Other
factors that may affect urinalysis results include failure
to collect a specimen during the day’s first voiding;
frequent urination; large dietary intake of vitamin C;
and urine with a pH value lower than 6.
Resources
ORGANIZATIONS

American Association of Kidney Patients. 100 S. Ashley Dr.,
#280, Tampa, FL 33602. (800) 749-2257. <http://
www.aakp.org>.
American Kidney Fund (AKF). Suite 1010, 6110 Executive
Boulevard, Rockville, MD 20852. (800) 638-8299.
<http://216.248.130.102/Default.htm>.

Maureen Haggerty

Methenamine
For adults and children 12 years and over, the
usual dosage is 1 gram, taken either twice a day or
four times a day, depending on the form in which the
drug comes. For children aged 6–12 years, the dosage
ranges from 500 mg taken 2–4 times a day to 1 gram
taken twice a day, again depending on the form of the
drug. For children under 6 years, a physician must
determine the dose.
This medicine will not work properly unless the
urine is acidic, with a pH reading of 5.5 or below. The
physician who prescribes the medicine will explain
how to test the urine’s acidity. The physician also
may suggest diet changes that will make the urine
more acidic, such as eating more protein, drinking
cranberry juice, eating plums and prunes, but avoiding
most other fruits, and cutting down on milk and other
dairy products. Antacids also should be avoided.
Nalidixic acid

Urinary anti-infectives
Definition
Urinary anti-infectives are medicines used to treat
or prevent infections of the urinary tract—the passage
through which urine flows from the kidneys out of the
body.

Purpose
Normally, no bacteria or other disease-causing
organisms live in the bladder. Likewise, the urethra—
the tube-like structure that carries urine from the
bladder out of the body—usually has either no bacteria
or not enough to cause problems. But the bladder,
urethra, and other parts of the urinary tract may
3854

The recommended dosage for adults and children
12 years and older is 1 gram every 6 hours. If the
medicine is taken for more than one or two weeks,
the dosage may be decreased to 500 mg every 6 hours.
A physician must determine the correct dosage for
children 3 months to 12 years old. Children under 3
months should not take this medicine because it causes
bone problems in young animals and could have the
same effect in young children.
Nitrofurantoin
CAPSULES, TABLETS, OR LIQUID. The usual dose for
adults and teenagers is 50–100 mg every six hours.
EXTENDED-RELEASE CAPSULES. For adults and children 12 years and older, the usual dosage is 100 mg every
12 hours for seven days.

GALE ENCYCLOPEDIA OF MEDICINE

Precautions
Methenamine
People with certain medical conditions may have
problems if they take this medicine. For example,
people with severe liver disease may have worsened
symptoms of their disease. And people who are
dehydrated or who have severe kidney disease may
be more likely to have side effects that affect the
kidneys.
Nalidixic acid
Some people feel drowsy, dizzy, or less alert than
usual when using this drug. The medicine may also
cause blurred vision or other vision changes. Because
of these possible problems, anyone who takes nalidixic
acid should not drive, operate machinery, or do anything
else that might be dangerous until they have found out
how the drugs affect them.
Nalidixic acid may increase sensitivity to sunlight.
Even brief exposure to sun can cause a severe sunburn or
a rash. While being treated with this medicine, avoid
being in direct sunlight, especially between 10 a.m. and
3 p.m.; wear a hat and tightly woven clothing that
covers the arms and legs; use a sunscreen with a skin
protection factor (SPF) of at least 15; protect the lips
with a sun block lipstick; and do not use tanning beds,
tanning booths, or sunlamps.
Diabetic patients should be aware that this medicine may cause false results on some urine sugar tests.
Check with a physician before making any changes in
diet or diabetes medicine based on the results of a
urine test.
In laboratory studies, nalidixic acid interferes with
bone development in young animals. The drug’s
effects have not been studied in pregnant women, but
because of its effects in animals, it is not recommended
for use during pregnancy.
This medicine generally does not cause problems
in nursing babies whose mothers take it. However,
nursing babies with glucose-6-phosphate dehydrogenase (G6PD) deficiency (an inherited disorder that
affects mainly black males) may have blood problems
if their mothers take nalidixic acid.
People with certain medical conditions may be
more likely to have particular side effects if they take
GALE ENCYCLOPEDIA OF MEDICINE

this medicine. For example, people with a history of
seizures or severe hardening of the arteries in the brain
may be more likely to have side effects that affect the
nervous system. People with glucose-6-phosphate
dehydrogenase (G6PD) deficiency are more likely to
have side effects that affect the blood. Also, people
with liver disease or severe kidney disease have an
increased chance of having any of the drug’s possible
side effects.
Nitrofurantoin
Pregnant women should not take this medicine
within two weeks of their delivery date and should
not use it during labor and delivery, as this could
cause problems in the baby.
Women who are breastfeeding should check with
their physicians before using this medicine. It passes
into breast milk and could cause problems in nursing
babies whose mothers take it. This is especially true of
babies with glucose-6-phosphate dehydrogenase
(G6PD) deficiency. The medicine also should not be
given directly to babies up to one month of age, as they
are particularly sensitive to its effects.
Older people may be more likely to have side
effects when taking nitrofurantoin, because they are
more sensitive to the drug’s effects.
Taking nitrofurantoin may cause problems for
people with certain medical conditions. Side effects
may be greater, for example, in people with lung
disease or nerve damage. In people with kidney disease,
the medicine may not work as well as it should, but
may cause more side effects. Those with glucose6-phosphate dehydrogenase (G6PD) deficiency who
take nitrofurantoin may develop anemia.
Diabetic patients should be aware that this medicine may cause false results on some urine sugar tests.
They should check with a physician before making any
changes in diet or diabetes medicine based on the
results of a urine test.
General precautions for all urinary
anti-infectives
Symptoms should improve within a few days of
starting to take a urinary anti-infective. If they do not,
or if they become worse, check with a physician right
away. Patients who need to take this medicine for long
periods should see their physicians regularly, so that
the physician can check their progress.
Anyone who has had unusual reactions to urinary
anti-infectives in the past should let his or her physician
know before taking the drugs again. The physician
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Urinary anti-infectives

For all forms of nitrofurantoin, a physician must
determine the correct dose for children one month and
older, based on the child’s body weight. Children
under one month should not take this medicine.

Urinary anti-infectives

should also be told about any allergies to foods,
dyes, preservatives, or other substances. Patients taking
nalidixic acid should tell their physicians if they
have ever had reactions to related medicines such as
cinoxacin (Cinobac), ciprofloxacin (Cipro), enoxacin
(Penetrex), norfloxacin (Noroxin) or ofloxacin (Floxin),
all of which are also used to treat or prevent infections.
Anyone taking nitrofurantoin should let the physician
know if he or she has had an unusual reaction to medicines such as furazolidone (Furoxone) or nitrofurazone
(Furacin).

Side effects
Methenamine
Nausea and vomiting are not common but may
occur. These side effects do not need medical attention
unless they are severe. One side effect that should be
brought to a physician’s attention immediately is a
skin rash.
Nalidixic acid
Some side effects are fairly minor and are likely to
go away as the body adjusts to the drug. These include
dizziness, drowsiness, headache, nausea or vomiting,
stomach pain and diarrhea. Unless these problems
continue or are bothersome, they do not need medical
attention.
Other side effects, however, should have prompt
medical attention. Anyone who has changes in vision,
such as blurred vision, double vision, decreased vision,
changes in color vision, halos around lights, or notices
an excessive brightness of lights should check with a
physician immediately.

KEY TERMS
Altitude sickness—A set of symptoms that people
who normally live at low altitudes may have when
they travel to high altitudes. The symptoms include
nosebleed, nausea, and shortness of breath.
Anemia—A lack of hemoglobin–the compound in
blood that carries oxygen from the lungs throughout the body and brings waste carbon dioxide from
the cells to the lungs, where it is released.
Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Glaucoma—A condition in which pressure in the
eye is abnormally high. If not treated, glaucoma
may lead to blindness.
Glucose-6-phosphate dehydrogenase (G6PD)
deficiency—An inherited disorder in which the
body lacks an enzyme that normally protects red
blood cells from toxic chemicals. When people
with this condition take certain drugs, their red
blood cells break down, causing anemia. This may
also happen when they have a fever or an infection.
The condition usually occurs in males. About 10%
of black males have it, as do a small percentage of
people from the Mediterranean region.
Granule—A small grain or pellet. Medicines that
come in granule form usually are mixed with
liquids or sprinkled on food before they are taken.
Organism—An individual of some type of life form,
such as a plant or an animal.
pH—A measure of how acidic or alkaline something is. The pH scale ranges from 0 to 14. Values
below 7 are acidic; values above 7 are alkaline.
Seizure—A sudden attack, spasm, or convulsion.

Nitrofurantoin
This medicine may make the urine turn reddishyellow to brown. This is nothing to worry about.
Other possible side effects that do not need medical
attention unless they are severe include pain in the
stomach or abdomen, stomach upset, diarrhea, loss
of appetite, and nausea or vomiting.
Anyone who has chest pain, breathing problems,
fever, chills, or a cough while taking nitrofurantoin
should check with a physician immediately.
General advice on side effects for all urinary
anti-infectives
Other side effects are possible when taking any
urinary anti-infective. Anyone who has unusual
3856

symptoms while taking this type of medicine should
get in touch with his or her physician.

Interactions
Methenamine
Certain medicines may make methenamine less
effective. These include thiazide diuretics (water pills)
and medicines that make the urine less acid, such
as antacids, bicarbonate of soda, and the drugs acetazolamide (Diamox), dichlorphenamide (Daranide),
and methazolamide (Neptazane), which are used to
treat glaucoma, epilepsy, altitude sickness, and other
conditions.
GALE ENCYCLOPEDIA OF MEDICINE

People who are taking blood thinners (anticoagulants) may be more likely to have bleeding problems if
they take this medicine.
Nitrofurantoin
Nitrofurantoin may interact with many other medicines. For example, taking nitrofurantoin with certain
drugs that include methyldopa (Aldomet), sulfonamides
(sulfa drugs), vitamin K, and diabetes medicines taken
by mouth may increase the chance of side effects that
affect the blood. General side effects are more likely in
people who take nitrofurantoin with the gout drugs
probenecid (Benemid) or sulfinpyrazone (Anturane).
And the risk of side effects that involve the nervous
system is higher in people who take nitrofurantoin with
various drugs including lithium (Lithane), disulfiram
(Antabuse), other anti-infectives, and the cancer drugs
cisplatin (Platinol) and vincristine (Oncovin). Patients
who have had a DPT (diphtheria, tetanus, and pertussis)
vaccine within the last 30 days or who have one after
taking nitrofurantoin are also more likely to have side
effects that affect the nervous system. Because of the
many possible interactions, anyone taking nitrofurantoin should be sure to check with a physician before
combining it with any other medicine.

Urinary catheterization is employed in hospital
and nursing home settings to maintain urine output
in patients who are undergoing surgery, or who are
confined to the bed and physically unable to use a
bedpan. Critically ill patients who require strict monitoring of urinary output are also frequently
catheterized.
Intermittent insertion of a urinary catheter is a
treatment option for patients with certain types of urinary incontinence. Patients who are unable to completely
empty the bladder during urination (urinary retention),
or patients who have a bladder obstruction, may also
require intermittent urinary catheterization. Disabled
individuals with neurological disorders that cause
paralysis or a loss of sensation in the perineal area
may also use regular intermittent catheter insertion to
void their bladders.

Precautions
Because urinary catheterization carries a risk of
causing urinary tract infection (UTI), precautions
should be used to keep the catheter clean and free of
bacteria. Patients requiring intermittent catheterization should be well trained in the technique by a qualified health care professional.

General advice about interactions
Not every drug that may interact with a urinary
anti-infective is listed here. Be sure to check with a
physician or pharmacist before combining a urinary
anti-infective with any other prescription or nonprescription (over-the-counter) medicine.
Resources
PERIODICALS

Tucker, M. Susan. ‘‘Recurrent UTI: Who Should Treat
Herself ?’’Patient Care 26 (July 15, 1992): 259.

Nancy Ross-Flanigan

Urinary antiseptics see Urinary anti-infectives

Urinary catheterization
Definition
Urinary catheterization is the insertion of a catheter into a patient’s bladder. The catheter is used as a
conduit to drain urine from the bladder into an
attached bag or container.
GALE ENCYCLOPEDIA OF MEDICINE

Description
Intermittent catheterization is performed a minimum of four times a day by the patient or a care giver.
The genital area near the urethral opening is wiped
with an antiseptic agent, such as iodine. A lubricant
may be used to facilitate the entry of the catheter into
the urethra, and a topical local anesthetic may be
applied to numb the urethral opening during the procedure. One end of the catheter is placed in a container, and the other end is inserted into and guided
up the urethra until urine flow begins. When urine
flow stops, the catheter may be moved or rotated, or
the patient may change positions to ensure that all
urine has emptied from the bladder. The catheter is
then withdrawn, cleaned, and sterilized for the next
use. Recommended cleaning practices vary, from the
use of soap and water to submersion in boiling water
or a disinfectant solution. Some patients prefer to use
a new catheter with each insertion.
Nonintermittent catheterization, which is
initiated in a hospital or nursing home setting, uses
the same basic technique for insertion of the urinary
tract catheter. The catheter is inserted by a nurse or
other health care professional, and remains in the
3857

Urinary catheterization

Purpose

Nalidixic acid

Urinary diversion surgery

patient until bladder function can be maintained independently. When the catheter is removed, patients will
experience a pulling sensation and may feel some
minor discomfort. If the catheter is required for an
extended period of time, a long-term, indwelling
catheter, such as a Foley catheter, is used. To prevent
infection, it should be regularly exchanged for a new
catheter every three to six weeks.
Use of indwelling catheters should be restricted to
patients whose incontinence is caused by urinary tract
obstruction that can not be treated, and for which
alternative therapy is not feasible.

Preparation
If a patient wishes to perform intermittent catheterization himself, training in the technique by a qualified
health care professional is required. Basic instruction in
the anatomy, antiseptic techniques, catheter insertion,
and proper catheter care should be provided. Patients
learning chronic intermittent urinary catheterization
may also benefit from an ultrasound examination to
verify that they are completely emptying their bladder
during the procedure.

KEY TERMS
Bladder obstruction—A blockage of the bladder
caused by the presence of calculi (e.g., mineral
deposits) or an anatomic abnormality.
Catheter—A long, thin, flexible tube.
Foley catheter—A two-channel catheter with a
balloon on the bladder end of one channel. Once
inflated, the balloon keeps the catheter securely
in the bladder. The other channel of the catheter
facilitates the flow of urine out of the bladder.
Local anesthetic—Medication applied topically to
the skin or administered through an injection that
deadens a specific part of the body and inhibits the
sensation of pain.
Perineal area—The genital area between the vulva
and anus in a woman, and between the scrotum
and anus in a man.
Ultrasound examination—A diagnostic test that
uses sound waves to generate a picture of an
organ or organ system.
Urinary incontinence—The inability to control
one’s urine flow.

Aftercare
Patients using intermittent catheterization as a
treatment for incontinence will experience a period of
adjustment as they try to establish a catheterization
schedule that is adequate for their normal level of fluid
intake.
Antibiotics may be prescribed as a preventative
measure in long-term urinary catheterization patients
who are at risk for urinary tract infection.
A patient with an indwelling catheter must be
reassessed periodically to determine whether alternative treatment may be more effective in treating the
problem.

Normal results
When used correctly, catheterization facilitates
complete voiding of the bladder.
Resources
PERIODICALS

Hunt, Gillian M., Pippa Oakeshott, and Robert Whitaker.
‘‘Intermittent Catheterization: Simple, Safe, and
Effective but Underused.’’ British Medical Journal 312,
no. 7023 (Jan. 1996): 103-7.

Paula Anne Ford-Martin

Risks
Trauma to the urethra and/or bladder may result
from incorrect insertion of the catheter. Repeated irritation to the urethra during catheter insertion may
cause scarring and/or stricture, or narrowing, of the
urethra. The catheter may introduce bacteria into the
urethra and bladder, resulting in urinary tract infection. UTI can cause fever and inflammation of the
bladder and urethra. Patients who practice intermittent catheterization can reduce their risks for UTI
by using antiseptic techniques for insertion and
catheter care.
3858

Urinary diversion surgery
Definition
A urinary diversion involves removal of the urinary bladder and adjacent tissues and organs, and
re-routing of the urinary stream. This may involve
creation of an artificial opening in the abdomen called
an ostomy.
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A urinary diversion is created as a means to treat
cancer of the bladder, when conservative measures
have been unsuccessful, or when there is recurrence
of the disease invading the muscle wall. Congenital
deformities or traumatic injury may also necessitate
formation of a urinary diversion.

Description
Under general anesthesia, an incision is made in
the abdomen. The ureters (tubes that carry urine away
from the kidneys) are cut and tied. The bladder and
surrounding tissues are cut free and removed. The
ureters are then attached to a portion of the intestine.
The most common types of urinary diversion are:


Ileal conduit. Ureters are attached to a portion of the
small intestine, the ileum, one end of which is
brought through the abdominal wall as a conduit
for the urine, creating a stoma



Ureterosigmoidostomy. The ureters are attached to a
portion of the large intestine, the sigmoid, which
allows the urine to flow through the large intestine
and out through the rectum



Cutaneous ureterostomy. Bringing the detached
ureters through the abdominal wall and attaching it
to an opening in the skin

Preparation
As with any surgical procedure, the patient will be
required to sign a consent form after the procedure is
explained thoroughly. Blood and urine studies, along
with various x rays and an electrocardiogram (EKG),
may be ordered as the doctor deems necessary. If
creation of an ostomy is planned, the patient should
visit an enterostomal therapist, who will mark an
appropriate place on the abdomen for a stoma and
offer preoperative education on ostomy management.
Eating or drinking is prohibited after midnight the
night before the surgery. Oral anti-infectives, such as
neomycin, erythromycin, or kanamycin sulfate, may
be ordered to decrease bacteria in the intestine and
help prevent postoperative infection. A nasogastric
tube is inserted the day of surgery, or during surgery,
to remove gastric secretions and prevent nausea and
vomiting.

Aftercare

Following creation of an artificial opening to
drain the urine, ureteral stents (tubes that go through
the stoma and up into the ureters) are often inserted
and left in place to allow urine to drain freely from the
kidneys, without risk of blockage from swelling due
to surgery. The muscles are replaced and sewn
together. A transparent pouch is applied to the abdomen to collect urine, and attached to a bedside drainage bag. The incision is closed with sutures or clips
(‘‘staples’’), which are usually removed about a week
after surgery.

Postoperative care for the patient with a urinary
diversion, as with those who have had any major
surgery, involves monitoring of blood pressure,
pulse, respirations, and temperature. Breathing tends
to be shallow because of the effect of anesthesia, and
the patient is reluctant to breathe deeply and experience pain that is caused by the abdominal incision. The
patient is shown how to support the operative site
during deep breathing and coughing, and is given
pain medication as necessary. Fluid intake and output
are measured, and the operative site is observed for
color and amount of wound drainage. The nasogastric
tube will remain in place, attached to low intermittent
suction, until bowel activity resumes. Fluids and electrolytes are infused intravenously until the patient’s
diet can gradually be resumed, beginning with liquids.
The patient is usually able to move about in 8–24 hours
after surgery, and is discharged from the hospital in
5–10 days.

An alternative to a conventional urinary diversion
is the continent urinary diversion. In this surgical
procedure, a ‘‘false bladder’’ is constructed within
the abdomen, using several lengths of small or large
intestine. The ureters are sewn to this new reservoir for
urine and nipple valves which are created at two sites;
the abdominal wall for continence; and where the
ureters are implanted, to prevent reflux of urine back
to the kidneys. The patient is then taught to catheterize
the reservoir to drain urine at regular intervals during
the day. Although a continent diversion is not suitable
for every patient who requires urinary diversion, it is
an option to be considered.

If an ostomy has been placed, the patient and
close family members will be educated on how to
care for it. Determination of appropriate pouching
supplies and a schedule of how often to change the
pouch should be established. Regular assessment and
meticulous care of the skin surrounding the stoma is
important to maintain an adequate surface on which
to apply the pouch. The pouch should be connected to
a bedside drainage bag at night to prevent large
volumes of urine from collecting in the pouch.
Otherwise, the weight of the pouch could cause disruption of the pouch seal and leakage of urine onto the
surrounding skin. Often, an enterostomal therapist

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Urinary diversion surgery

Purpose

Urinary incontinence



Stoma flush or below the abdomen surface (retraction). Caused by insufficient stomal length, this may
be managed by use of special pouching supplies.
Elective revision of the stoma is also an option



Narrowing at the opening of the stoma (stenosis).
Often associated with infection around the stoma or
scarring, mild stenosis can be removed under local
anesthesia. Severe stenosis may require surgery for
stomal revision



Parastomal hernia. The bowel causes a bulge in the
abdominal wall next to the stoma. This is usually due
to placement of the stoma where the abdominal wall
is weak, or an overly large opening in the abdominal
wall. Use of an ostomy support belt and special
pouching supplies may be adequate. If severe, the
defect in the abdominal wall should be repaired and
the stoma moved to another location

KEY TERMS
Ischemia— A compromise in blood supply to body
tissues that causes tissue damage or death.
Ostomy—A surgically-created opening in the
abdomen for elimination of waste products (urine
or stool).

will visit the patient at home after discharge to help the
new ostomy patient make the transition back to normal daily activities.

Risks
Potential complications of urinary diversion surgery
include:


excessive bleeding

Resources



surgical wound infection

ORGANIZATIONS



thrombophlebitis (inflammation and blood clot to
veins in the legs)

United Ostomy Association, Inc. (UOA). 19772 MacArthur
Blvd., Suite 200, Irvine, CA 92612-2405. (800) 8260826. <http://www.uoa.org>.



pneumonia



pulmonary embolism (blood clot or air bubble in the
lungs’ blood supply)

Kathleen D. Wright, RN

Normal results
Complete healing is expected without complications. The amount of time required for recovery
from the surgery may vary depending of the patient’s
overall health status prior to surgery. The patient with
a urinary diversion, without other medical complications, should be able to resume all daily activities once
recovered from the surgery.

Abnormal results
The doctor should be made aware of any of the
following problems after surgery:


Increased pain, swelling, redness, drainage, or
bleeding in the surgical area



Headache, muscle aches, dizziness, or fever



Increased abdominal pain or swelling, constipation,
nausea, or vomiting
Stomal complications to be monitored include:



Stomal tissue death (necrosis). This occurs because
of inadequate blood supply, this is usually visible 12
to 24 hours after surgery and may require additional
surgery

3860

Urinary incontinence
Definition
Urinary incontinence is unintentional loss of urine
that is sufficient enough in frequency and amount to
cause physical and/or emotional distress in the person
experiencing it.

Description
Approximately 13 million Americans suffer from
urinary incontinence. Women are affected by the disorder more frequently than are men; one in 10 women
under age 65 suffers from urinary incontinence.
A study published in late 2002 found that between
21% and 29% of adult women in the workforce
reported at least one episode of urinary incontinence
each month. Older Americans, too, are more prone to
the condition. Twenty percent of Americans over age
65 are incontinent. In general, the condition is underrecognized and undertreated.
There are five major categories of urinary incontinence: overflow, stress, urge, functional, and reflex.
GALE ENCYCLOPEDIA OF MEDICINE



Overflow incontinence. Overflow incontinence is
caused by bladder dysfunction. Individuals with
this type of incontinence have an obstruction to the
bladder or urethra, or a bladder that doesn’t contract
properly. As a result, their bladders do not empty
completely, and they have problems with frequent
urine leakage.
Stress incontinence. Stress incontinence occurs when
an individual involuntarily loses urine after pressure is
placed on the abdomen (i.e., during exercise, sexual
activity, sneezing, coughing, laughing, or hugging).



Urge incontinence. Urge incontinence occurs when
an individual feels a sudden need to urinate, and
cannot control the urge to do so. As a consequence,
urine is involuntarily lost before the individual can
get to the toilet.



Functional incontinence. Individuals who have control over their own urination and have a fully functioning urinary tract, but cannot make it to the
bathroom in time due to a physical or cognitive disability, are functionally incontinent. These individuals may suffer from arthritis, Parkinson’s disease,
multiple sclerosis, or Alzheimer’s disease.





Hysterectomy or other gynecological surgery. Any
surgery involving the urogenital tract runs the risk of
damaging or weakening the pelvic muscles and causing incontinence.



Menopause. The absence of estrogen in the postmenopausal woman can cause the bladder to drop, or
prolapse.



Neurological conditions. The nervous system sends
signals to the bladder telling it when to start and stop
emptying. When the nervous system is impaired,
incontinence may result. Neurological conditions
such as multiple sclerosis, stroke, spinal cord injuries,
or a brain tumor may cause the bladder to contract
involuntarily, expelling urine without warning, or to
cease contractions completely, causing urinary
retention.



Obesity. Individuals who are overweight have undue
pressure placed on their bladder and surrounding
muscles.



Obstruction. A blockage at the bladder outlet may
permit only small amounts of urine to pass, resulting
in urine retention and subsequent overflow incontinence. Tumors, calculi, and scar tissue can all block
the flow of urine. A urethral stricture, or narrow
urethra caused by scarring or inflammation, may
also result in urine retention.

Reflex incontinence. Individuals with reflex incontinence lose control of their bladder without warning.
They typically suffer from neurological impairment.

In some cases, an individual may develop shortterm or acute incontinence. Acute incontinence may
occur as a symptom or by-product of illness, as a
side effect of medication, or as a result of dietary
intake. The condition is typically easily resolved once
the cause is determined and addressed.

Acute incontinence is a temporary condition
caused by a number of factors, including:


Bladder irritants. Substances in the urine that irritate
the bladder may cause the bladder muscle to malfunction. The presence of a urinary tract infection
and the ingestion of excess caffeine can act as irritants. Highly concentrated urine resulting from low
fluid intake may also irritate the bladder.



Constipation. Constipation can cause incontinence in
some individuals. Stool that isn’t passed presses
against the bladder and urethra, triggering urine
leakage.



Illness or disease. Diabetes can greatly increase urine
volume, making some individuals prone to incontinence. Other illnesses may temporarily impair the
ability to recognize and control the urge to urinate,
or to reach the toilet in time to do so.



Medications and alcohol. Medications that sedate,
such as tranquilizers and sleeping pills, can interfere
with the proper functioning of the urethral nerves
and bladder. Both sedatives and alcohol can also
impair an individual’s ability to recognize the need
to urinate, and act on that need in a timely manner.
Other medications such as diuretics, muscle

Causes and symptoms
Urinary incontinence can be caused by a wide
variety of physical conditions, including:






Childbirth. Childbirth can weaken the pelvic muscles
and cause the bladder to lose some support from
surrounding
muscles,
resulting
in
stress
incontinence.
Dysfunction of the bladder and/or the urinary
sphincter. In a continent individual, as the bladder
contracts, the outlet that releases urine into the urethra (bladder sphincter) opens and urine exits the
body. In individuals with overflow incontinence,
bladder contractions and dilation of the sphincter
do not occur at the same time.
Enlarged prostate. In men, an enlarged prostate
gland can obstruct the bladder, causing overflow
incontinence.

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Urinary incontinence



Urinary incontinence
Strengthening the pelvic floor muscles by performing Kegel exercises helps to alleviate stress incontinence in women. Contract
the pelvic floor muscles as if stopping an imaginery flow of urine. Hold for 10 seconds and repeat. (Illustration by Electronic
Illustrators Group.)

relaxants, and blood pressure medication can also
affect bladder function.




Behavior modification therapy. Behavior modification
is a psychological approach to the treatment of urinary
incontinence in which patients gradually increase the
length of the time interval between voidings and
‘‘retrain’’ the bladder in other ways. It is reported to
be highly effective in treating urge incontinence.



Biofeedback. The use of sensors to monitor temperature
and muscle contractions in the vagina to help incontinent patients learn to control their pelvic muscles.



Collagen injections. Collagen injected in the tissue
surrounding the urethra can provide urethral support for women suffering from stress incontinence.



External occlusive devices. A new single-use disposable urethral cap is available without a prescription
as of late 2002 for women suffering from stress urinary incontinence. The cap is noninvasive and appears
to be quite effective in managing incontinence.



Inflatable urethral insert. Sold under the trade name
Reliance, this disposable incontinence balloon for
women is inserted into the urethra and inflated to
prevent urine leakage.



Intermittent urinary catheterization. The periodic
insertion of a catheter into a patient’s bladder to
drain urine from the bladder into an attached bag
or container.

Surgery. Men who undergo prostate surgery can
suffer from temporary stress incontinence as a result
of damage to the urethral outlet.

Diagnosis
Urinary incontinence may be diagnosed by a general practitioner, urologist, or gynecologist. If the
patient is over age 65, a geriatrician may diagnose
and treat the condition. A thorough medical history
and physical examination is typically performed, along
with specific diagnostic testing to determine the cause
of the incontinence. Diagnostic testing may include
x rays, ultrasound, urine tests, and a physical examination of the pelvis. It may also include a series of
exams that measure bladder pressure and capacity and
the urinary flow (urodynamic testing). The patient
may also be asked to keep a diary to record urine
output, frequency, and any episodes of incontinence
over a period of several days or a week.

Treatment
There are numerous invasive and noninvasive
treatment options for urinary incontinence:
3862

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Bladder neck—The place where the urethra and
bladder join.
Bladder sphincter—The outlet that releases urine
into the urethra.



Sacral nerve stimulation (SNS). Also known as
sacral neuromodulation, SNS is a procedure in
which a surgeon implants a device that sends continuous stimulation to the sacral nerves that control the
urinary sphincter. The FDA approved sacral nerve
stimulation for the treatment of urinary urge incontinence in 1997 and for urinary frequency in 1999.



Surgery. Bladder neck suspension surgery is used to
correct female urinary stress incontinence. Surgical
techniques such as the Marshall-Marchetti-Krantz
and Burch procedures use sutures to raise and support the bladder neck and urethra. A sling procedure,
which uses a strip of biocompatible material or the
patient’s own muscle or tissue as a supportive sling
under the urethra and bladder neck, may also be used
to treat stress incontinence. Bladder enlargement
surgery may be recommended to treat incontinent
men and women with unusually small bladders.



Urinary sphincter implant. An artificial urinary
sphincter may be used to treat incontinence in men
and women with urinary sphincter impairment.



Vaginal inserts. Devices constructed of silicone or
other pliable materials that can be inserted into a
woman’s vagina to support the urethra.

Calculi (singular, calculus)—Mineral deposits that
can form a blockage in the urinary system.
Occlusive—Closing off. One of the newest treatments for stress urinary incontinence in women is
an external occlusive single-use cap that covers the
urethral opening.
Perineal area—The genital area between the vulva
and anus in a woman, and between the scrotum
and anus in a man.
Sacral nerves—The five pairs of nerves that arise
from the lowermost segments of the spinal cord
and control bladder, bowel, and pelvic functions.
Stimulation of the sacral nerves by an implanted
device is a newer treatment for urinary incontinence.



Medication. Estrogen hormone replacement therapy
can help improve pelvic muscle tone in postmenopausal women. Other medications, including flurbiprofen, capsaicin and botulinum toxin, are sometimes
prescribed to relax the bladder muscles or to tighten
the urethral sphincter. As of late 2002, newer medications for the treatment of urinary incontinence were
undergoing clinical trials. One of these drugs, duloxetine, differs from present medications in targeting the
central nervous system’s control of the urge to urinate
rather than the smooth muscle of the bladder itself.



Pelvic toning exercises. Exercises to tone the pelvic
muscle can help alleviate stress incontinence in both
men and women. These exercises involve tightening
the muscles of the pelvic floor, and are also known as
Kegel or PC muscle exercises.



Perineal stimulation. Perineal stimulation is used to
treat stress incontinence. The treatment uses a probe
to deliver a painless electrical current to the perineal
area muscles. The current tones the muscle by contracting it.



Permanent catheterization. A permanent, or indwelling, catheter may be prescribed for chronic incontinence that doesn’t respond to other treatments. A
Foley catheter is usually used for urinary catheterization. One end is inserted through the urethra and
into the bladder, and the external end is attached to a
plastic reservoir bag that the patient may wear on the
leg. A second alternative is a permanent catheter,

GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Left untreated, incontinence can cause physical
and emotional upheaval. Individuals with long-term
incontinence suffer from urinary tract infections, and
skin rashes and sores. Incontinence can also affect
their self-esteem and cause depression and social withdrawal. They frequently stop participating in physical
activities they once enjoyed because of the risk of
embarrassing ‘‘accidents.’’ However, with the wide
variety of treatment options for incontinence available
today, the prognosis for incontinent patients is promising. If incontinence cannot be stopped, it can be
improved in the majority of cases.

Prevention
Women who are pregnant or who have gone
through childbirth can reduce their risk for stress
incontinence by strengthening their perineal area muscles with Kegel exercises. Men who have undergone
prostate surgery may also benefit from pelvic muscle
3863

Urinary incontinence

called a suprapubic tube, surgically inserted into the
bladder. The tube exits the body through the abdomen near the pubic bone, where it is attached to a
drainage bag. As infection may result, this treatment
should be reevaluated periodically, and the possibility of alternative treatment addressed.

KEY TERMS

Urine culture

exercises. Men and women should consult with their
doctor before initiating any type of exercise program.

National Kidney and Urologic Diseases Information
Clearinghouse. 3 Information Way, Bethesda, MD
20892-3580. (800) 891-5390.

Resources
Paula Anne Ford-Martin
Rebecca J. Frey, PhD

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Urinary Incontinence.’’ Section 17, Chapter 215 In
The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck Research
Laboratories, 2004.
PERIODICALS

Amundsen, C. L., and G. D. Webster. ‘‘Sacral
Neuromodulation in an Older, Urge-Incontinent
Population.’’ American Journal of Obstetrics and
Gynecology 187 (December 2002): 1462–1465.
Bachmann, G., and B. Wiita. ‘‘External Occlusive Devices
for Management of Female Urinary Incontinence.’’
Journal of Women’s Health (Larchmont) 11 (November
2002): 793–800.
Burgio, K. L. ‘‘Influence of Behavior Modification on
Overactive Bladder.’’ Urology 60, no.5, Supplement 1
(November 2002): 72–76.
Burgio, K. L., P. S. Goode, J. L. Locher, et al. ‘‘Behavioral
Training With and Without Biofeedback in the
Treatment of Urge Incontinence in Older Women:
A Randomized Controlled Trial.’’ Journal of the
American Medical Association 288 (November 13,
2002): 2293–2299.
Haeusler, G., H. Leitich, M. van Trotsenburg, et al. ‘‘Drug
Therapy of Urinary Urge Incontinence: A Systematic
Review.’’ Obstetrics and Gynecology 100, no. 5, Part 1
(November 2002): 1003–1016.
Palmer, M. H., and S. Fitzgerald. ‘‘Urinary Incontinence in
Working Women: A Comparison Study.’’ Journal of
Women’s Health (Larchmont) 11 (December 2002):
879–888.
Viktrup, L. ‘‘Female Stress and Urge Incontinence in Family
Practice: Insight Into the Lower Urinary Tract.’’
International Journal of Clinical Practice 56 (November
2002): 694–700.
Yoshimura, N., and M. B. Chancellor. ‘‘Current and Future
Pharmacological Treatment for Overactive Bladder.’’
Journal of Urology 168 (November 2002): 1897–1913.
ORGANIZATIONS

American Foundation for Urologic Disease. 1128 North
Charles St., Baltimore, MD 21201. (800) 242-2383.
<http://www.afud.org>.
American Urological Association (AUA). 1120 North
Charles Street, Baltimore, MD 21201. (410) 727-1100.
<www.auanet.org>.
Center for Biologics Evaluation and Research (CBER), U.
S. Food and Drug Administration (FDA). 1401
Rockville Pike, Rockville, MD 20852-1448. (800) 8354709 or (301) 827-1800. <www.fda.gov/cber>.
National Association for Continence. P.O. Box 8310,
Spartanburg, SC 29305-8310. (800) 252-3337. <http://
www.nafc.org>.
3864

Urinary tract infections see Cystitis;
Nongonococcal urethritis; Urethritis
Urine concentration test see Kidney function
tests

Urine culture
Definition
A urine culture is a diagnostic laboratory test
performed to detect the presence of bacteria in the
urine (bacteriuria).

Purpose
Culture of the urine is a method of diagnosis for
urinary tract infection that determines the number of
microorganisms present in a given quantity of urine.

Precautions
If delivery of the urine specimen to the laboratory
within one hour of collection is not possible, it should
be refrigerated. The health care provider should be
informed of any antibiotics currently or recently taken.

Description
There are several different methods for collection
of a urine sample. The most common is the midstream
clean-catch technique. Hands should be washed
before beginning. For females, the external genitalia
(sex organs) are washed two or three times with a
cleansing agent and rinsed with water. In males, the
external head of the penis is similarly cleansed and
rinsed. The patient is then instructed to begin to urinate, and the urine is collected midstream into a sterile
container. In infants, a urinary collection bag (plastic
bag with an adhesive seal on one end) is attached over
the labia in girls or a boy’s penis to collect the
specimen.
Another method is the catheterized urine specimen in which a lubricated catheter (thin rubber tube)
is inserted through the urethra (tube-like structure in
GALE ENCYCLOPEDIA OF MEDICINE

Bacteriuria—The presence of bacteria in the urine.

which urine is expelled from the bladder) into the
bladder. This avoids contamination from the urethra
or external genitalia. If the patient already has a urinary catheter in place, a urine specimen may be collected by clamping the tubing below the collection port
and using a sterile needle and syringe to obtain the
urine sample; urine cannot be taken from the drainage
bag, as it is not fresh and has had an opportunity to
grow bacteria at room temperature. On rare occasions, the health care provider may collect a urine
sample by inserting a needle directly into the bladder
(suprapubic tap) and draining the urine; this method is
used only when a sample is needed quickly.
Negative culture results showing no bacterial
growth are available after 24 hours. Positive results
require 24–72 hours to complete identification of the
number and type of bacteria found.

Preparation
Drinking a glass of water 15–20 minutes before
the test is helpful if there is no urge to urinate. There
are no other special preparations or aftercare required
for the test.

Risks
There are no risks associated with the culture test
itself. If insertion of a urinary catheter (thin rubber
tube) is required to obtain the urine, there is a slight
risk of introducing infection from the catheter.

Normal results
No growth of bacteria is considered the normal
result, and this indicates absence of infection.

Abnormal results
Abnormal results, or a positive test, where bacteria are found in the specimen, may indicate a urinary
tract infection. Contamination of the specimen from
hair, external genitalia, or the rectum may cause a
false-positive result. Identification of the number and
type of bacteria, with consideration of the method
used in obtaining the specimen, is significant in
diagnosis.
GALE ENCYCLOPEDIA OF MEDICINE

Escherichia coli causes approximately 80% of
infections in patients without catheters, abnormalities of the urinary tract, or calculi (stones). Other
bacteria that account for a smaller portion of
uncomplicated infections include Proteus klebsiella
and Enterobacter.
Resources
ORGANIZATIONS

American Foundation for Urologic Disease. 300 West Pratt
St., Suite 401, Baltimore, MD 21201.

Kathleen D. Wright, RN

Urine flow test
Definition
A urine flow test evaluates the speed of urination,
or amount voided per second, and the total time of
urination.

Purpose
A urine flow test is utilized to determine bladder
function abnormalities, including a narrowed or
obstructed urethra (the outflow passage from the
bladder) and a weakened bladder muscle (detrusor).

Description
During a urine flow test, the patient urinates into
a uroflowmeter, a funnel-shaped device that reads,
measures, and computes the rate and amount of
urine flow. The test takes approximately 10 minutes.

Preparation
The patient is prohibited from urinating at least
two hours before the procedure.

Normal results
Average urine flow rates vary depending on age
and gender.

Abnormal results
A urine flow test can indicate problems in bladder
function, such as an obstruction, that will need further
tests to diagnose.
3865

Urine flow test

KEY TERMS

Uterine fibroid embolization

KEY TERMS
Detrusor muscle—Bladder muscle.
Urethra—Passageway that carries urine from the
bladder.

Resources
BOOKS

Walsh, Patrick C., et al., editors. Campbell’s Urology.
Philadelphia: W. B. Saunders Co., 1998.

J. Ricker Polsdorfer, MD

Urography see Intravenous urography
Urticaria see Hives
Uterine cancer see Endometrial cancer

create pressure on other organs, the physician and
patient may discuss treatment options. A woman still
planning to have children may need to have fibroids
removed to ensure they do not interfere with the ability of a fertilized egg to implant on her uterine lining.
In rare cases, fibroids cause such severe and sharp
pelvic pain that emergency treatment is required.
Although some medications may help ease the
symptoms of fibroids or even slow their growth, they
are not long-term solutions to the fibroid growths.
Surgery also can remove the fibroids. Myomectomy
is the most common surgery option still used to treat
fibroids because it does not involve removing the
uterus. In severe cases, women may have a hysterectomy and have their uterus removed.
The development of uterine fibroid embolization
has offered women a non-surgical alternative to treating fibroids that are causing symptoms. It also is effective for treating multiple fibroids.

Precautions

Uterine fibroid embolization
Definition
Uterine fibroids are growths in the muscular tissue
of the womb (uterus). Uterine fibroid embolization is
non-surgical removal of the growths through the use
of a tubular device called a catheter.

Purpose
It is estimated that between 20% and 40% of
women over age 35 years have fibroids. These noncancerous tumors of the uterus, also called myomas,
fibromyomas, or leiomyomas, can be as tiny as a pea
or grow to as large as a cantaloupe. They grow along
the muscular wall of the uterus and are made of both
muscle and fiber-like tissue. Although they are not
cancerous, they can cause uncomfortable symptoms
in women, particularly pain and a feeling of pressure in
the area between the hip bones (the lower pelvic area).
Some women experience a feeling that they constantly
need to urinate. Others may feel pressure in the bowel,
and experience bloating or constipation. Sometimes,
fibroids cause heavy menstrual bleeding and lengthier
menstrual periods.
In some cases, women need no treatment for
fibroids, since the growths may cause no symptoms
or may stop causing symptoms when a woman reaches
menopause. However, when the fibroids cause heavy
bleeding that can lead to anemia, pelvic pain, and
3866

Although uterine fibroid embolization has been
shown in many studies to be effective, some physicians
say it is a relatively new procedure that lacks long-term
data on its effectiveness. Estimates show that at least
90% of women who have the procedure will have relief
of symptoms and no return of fibroids. Some women
have reportedly stopped having menstrual periods
following the procedure. Since the long-term effects
of uterine fibroid embolization on future pregnancies
has not been studied extensively, patients still wanting
to have children should discuss the latest research and
fibroid treatment options with their physicians.
Overall, however, the treatment is a safer and less
invasive alternative than surgery.

Description
Uterine fibroid embolization usually is performed
in a hospital, but sometimes in an outpatient imaging
center. An interventional radiologist normally performs the procedure. Interventional radiologists are
physicians who are specially trained to use x rays to see
inside the body while guiding narrow tubes called
catheters through blood vessels to diagnose or treat
various diseases.
Uterine fibroid embolization also may be called
uterine artery embolization. This is because the procedure injects tiny particles, called embolic agents, into
the artery that supplies blood to the fibroid tumor,
blocking off the tumor’s blood supply. The radiologist
reaches the uterine artery by first making a small nick
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The radiologist can view the progress of the catheter using a moving x-ray technique called fluoroscopy.
When the catheter reaches the artery supplying blood
to the fibroid tumor, the radiologist injects the embolic
agents, which are only about the size of grains of sand.
When they gather together, they form a clot and since
no more blood can reach the fibroids, they eventually
will shrink and disappear. If a woman has fibroids on
both sides, the radiologist will guide the catheter
around to repeat the procedure on the other side of
the uterus. After removing the catheter, the medical
team will clean the puncture area and cover it with a
bandage. They also remove the Foley catheter. The
entire procedure takes about one hour and should cost
less than hysterectomy or other surgical treatments.
Most insurance companies will pay for uterine fibroid
embolization.

Preparation
When the embolization is scheduled, the hospital or
facility should provide instructions regarding medications or food and drink to avoid prior to the procedure.
Once a patient checks in, a nurse or technician may
draw blood for routine tests and a nurse or radiologic
technologist who specializes in vascular procedures will
start an intravenous (IV) line through which the patient
will receive antibiotics to prevent infection.

Aftercare
Although uterine fibroid embolization is an outpatient procedure, patients may stay in a recovery area
for up to 23 hours. When patients are discharged, they
will receive specific instructions about follow-up care
and medication for relief of pain and swelling. Uterine
fibroid embolization rarely requires stitches. Patients
may be advised to use a stool softener while taking
some of the aftercare medications to avoid constipation. They will be instructed to drink plenty of fluids
for the first week following the procedure. Normally,
the patient should avoid soaking in hot baths for the
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anemia—A condition in which the blood has a low
number of red blood cells, low hemoglobin, or low
total blood volume.
Artery—One of several tubular branches of muscular and elastic walled vessels that carry blood
from the heart through the body.
Femoral artery—The chief artery of the thigh.
Groin—The fold that marks the meeting of the
lower abdomen and the inner thigh.

first three days and should not drive a car for about
three days following uterine fibroid embolization.
Strenuous activity, such as climbing stairs, squatting, or lifting heavy objects should be avoided for
about one week. Patients also should not stand in
one position for long periods of time in the first week
following the procedure. It is usually best to avoid
heavy exercise routines, athletic activity and sexual
relations for about up to month. Women also may be
advised to avoid using tampons for menstrual periods
for up to three months following uterine fibroid embolization, substituting sanitary pads.

Risks
Most patients experience moderate to severe pain
and cramping for several hours after the procedure
and some will have nausea and fever. There is a risk
of infection from uterine fibroid embolization, but the
risk is small and the infection usually can be controlled
by antibiotics. A small percentage (about one percent)
of women may experience an injury to the uterus or an
infection that may lead to a later hysterectomy. There
also is a small risk that a woman will stop having
periods after uterine fibroid embolization. Overall,
these risks are relatively low compared to surgical
removal of fibroids.

Normal results
About 90% of women who have the procedure
experience significant or complete relief of heavy
bleeding, pain, and other symptoms. Patients usually
will follow up with their gynecologist about two weeks
following the procedure. Recurrence of fibroids is
rare, though long-term studies of 10 years or more
have shown that about 10% of patients may need
additional treatment after 10 years. Additional studies
continue on the procedure’s long-term effectiveness.
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Uterine fibroid embolization

(about one-quarter of an inch) in the patient’s skin in
the groin area. From this incision, the radiologist can
inset the catheter into the femoral artery and then
guide the catheter toward the area of the uterus.
Patients do not feel the catheter as it moves along the
artery and a nurse or anesthesiologist will provide
drugs for pain relief at the insertion site. The nurse
or a technologist also will insert a Foley catheter into
the patient s bladder. This keeps the bladder emptied
so that the radiologist can have a better picture of the
uterus and the anatomy that surrounds the uterus
during the procedure.

Uterine fibroids

Resources

women are much more likely to develop uterine
fibroids.

PERIODICALS

Johnson, Kate. ‘‘Inform Patients of Long-term UFE
Outcomes.’’ Family Practice News (Dec. 15,
2004):40–41.
Johnson, Kate. ‘‘Recovery Fast in Uterine Fibroid
Embolization: Most Patients Recover Within Two
Weeks.’’ Family Practice News (Aug. 15, 2002):40–41.
‘‘Uterine Fibroid Embolization Is Minimally Invasive
Alternative to Hysterectomy.’’ Women s Health Weekly
(Dec. 23, 2004):181.

Fibroids are divided into different types, depending on the location. Submucous fibroids are found in
the uterine cavity; intramural fibroids grow on the
wall of the uterus; and subserous fibroids are located
on the outside of the uterus. Many fibroids are so large
that they fit into more than one category. The symptoms caused by fibroids are often related to their
location.

ORGANIZATIONS

National Uterine Fibroids Foundation. 1132 Lucero Street,
Camarillo, CA 93010. 805-482-2698. <http://
www.nuff.org>.
Society of Interventional Radiology. 10201 Lee Highway,
Suite 500, Fairfax, VA 22030. 703-691-1805. <http://
www.sirweb.org>.
OTHER

Brown, Linda. Alternatives to Hysterectomy: New
Technologies, More Options. U.S. Food and Drug
Administration website, 2001. <http://www.fda.gov/
fdac/features/2001/601_tech.html>.
Uterine Artery Fibroid Embolization.Georgetown University
Hospital website, 2003. <http://www.fibroidoptions
.com/embol.htm>.

Causes and symptoms
No one knows exactly what causes fibroids.
However, the growth of fibroids appears to depend
on the hormone estrogen. Fibroids often grow larger
when estrogen levels are high, as in pregnancy.
Medications that lower the estrogen level can cause
the fibroids to shrink.
The signs and symptoms of fibroids include:


Heavy uterine bleeding. This is the most common
symptom, occurring in 30% of women who have
fibroids. The excess bleeding usually happens during
the menstrual period. Flow may be heavier, and
periods may last longer. Women who have submucous or intramural fibroids are most likely to have
heavy uterine bleeding.



Pelvic pressure and pain. Large fibroids that press on
nearby structures such as the bladder and bowel can
cause pressure and pain. Larger fibroids tend to
cause worse symptoms.



Infertility. This is a rare symptom of fibroids. It
probably accounts for less than 3% of infertility
cases. Fibroids can cause infertility by compressing
the uterine cavity. Submucous fibroids can fill the
uterine cavity and interfere with implantation of the
fertilized egg.



Miscarriage. This is also an unusual symptom of
fibroids, probably accounting for only a tiny fraction
of the miscarriages that occur.



Pregnancy complications. Fibroids can greatly
increase in size during pregnancy, because of
increased levels of estrogen. They can cause pain,
and even lead to premature labor.

Teresa G. Odle

Uterine fibroids
Definition
Uterine fibroids (also called leiomyomas or myomas) are benign growths of the muscle inside the uterus.
They are not cancerous, nor are they related to cancer.
Fibroids can cause a wide variety of symptoms, including heavy menstrual bleeding and pressure on the
pelvis.

Description
Uterine fibroids are extremely common. About
25% of women in their reproductive years have noticeable fibroids. There are probably many more women
who have tiny fibroids that are undetected.
Fibroids develop between the ages of 30–50. They
are never seen in women less than 20 years old. After
menopause, if a woman does not take estrogen,
fibroids shrink. It appears that African-American
3868

Diagnosis
A health care provider can usually feel fibroids
during a routine pelvic examination. Ultrasound can
be used to confirm the diagnosis, but this is not
necessary.
GALE ENCYCLOPEDIA OF MEDICINE

Uterine fibroids

Fallopian tubes

Ovary
Uterus

Fibroids
(benign tumors)

Cervix
Vagina

Uterine fibroids are benign growths of uterine muscle and are very common. They are divided into three types, depending on the
location. Submucous fibroids are found in the uterine cavity; intramural fibroids grow on the wall of the uterus; and subserous
fibroids are located outside of the uterus. (Illustration by Electronic Illustrators Group.)

Treatment



Hysterectomy. This involves surgical removal of the
uterus, and it is the only real cure for fibroids. In fact,
25% of hysterectomies are performed because of
symptomatic fibroids. By the time a woman has a
hysterectomy for fibroids, she has usually endured
several years of worsening symptoms. That’s because
fibroids tend to grow over time. A gynecologist can
remove a fibroid uterus during either an abdominal
or a vaginal hysterectomy. The choice depends on the
size of the fibroids and other factors such as previous
births and previous surgeries.



Myomectomy. In this surgical procedure only the
fibroids are removed; the uterus is repaired and left
in place. This is the surgical procedure many women
choose if they are not finished with childbearing. At
first glance, it seems that this treatment is a middle
ground between observation and hysterectomy.
However, myomectomy is actually a difficult surgical procedure, more difficult than a hysterectomy.
Myomectomy often causes significant blood loss,
and blood transfusions may be required. In addition,
some fibroids are so large, or buried so deeply within

Not all fibroids cause symptoms. Even fibroids
that do cause symptoms may not require treatment.
In the majority of cases, the symptoms are inconvenient
and unpleasant, but do not result in health problems.
Occasionally, fibroids lead to such heavy menstrual bleeding that the woman becomes severely anemic. In these cases, treatment of the fibroids may be
necessary. Very large fibroids are much harder to
treat. Therefore, many doctors recommend treatment
for moderately-sized fibroids, in the hopes of preventing them from growing into large fibroids that cause
worse symptoms.
The following are possible treatment plans:


Observation. This is the most common plan. Most
women already have symptoms at the time their
fibroids are discovered, but feel that they can tolerate
their symptoms. Therefore, no active treatment is
given, but the woman and her physician stay alert
for signs that the condition might be getting worse.

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Uveitis

KEY TERMS
Anemia—Low blood count.
GnRH antagonists—A group of medications that
affect the reproductive hormones. These medications are used to treat fibroids, endometriosis, and
infertility.
Hysterectomy—Removal of the uterus (with or
without removal of the ovaries) by surgery. The
surgery can be performed through an incision in
the abdomen, or the uterus can be removed
through the vagina.
Menopause—The end of the reproductive years,
signaled by the end of menstrual periods. Also
known as ‘‘the change.’’
Osteoporosis—Brittle bones commonly found in
elderly women.

the wall of the uterus, that it is not possible to save
the uterus, and a hysterectomy must be done, even
though it was not planned. There are exceptions to
this, however. Sometimes, fibroids grow on a stalk
(pedunculated fibroids), and these are easy to
remove.


Medical treatment. Since fibroids are dependent on
estrogen for their growth, medical treatments that
lower estrogen levels can cause fibroids to shrink.
A group of medications known as GnRH antagonists can dramatically lower estrogen levels. Women
who take these medications for three to six months
find that their fibroids shrink in size by 50% or more.
They usually experience dramatic relief of their
symptoms of heavy bleeding and pelvic pain.

Unfortunately, GnRH antagonists cause unpleasant side effects in over 90% of women. The therapy is
usually used for only three months, and should not be
used for more than six months because the risk of
developing brittle bones (osteoporosis) begins to rise.
Once the treatment is stopped, the fibroids begin to
grow back to their original size. Within six months,
most of the old symptoms return. Therefore, GnRH
agonists cannot be used as long-term solution. At the
moment, treatment with GnRH antagonists is used
mainly in preparation for surgery (myomectomy or
hysterectomy). Shrinking the size of the fibroids
makes surgery much easier, and reducing the heavy
bleeding allows a woman to build up her blood count
before surgery.
Fibroids can cause problems during pregnancy
because they often grow in size. Large fibroids can
3870

cause pain and lead to premature labor. Fibroids
cannot be removed during pregnancy because of
the risk of injury to the uterus and hemorrhage.
GnRH antagonists cannot be used during pregnancy.
Treatment is limited to pain medication and medication to prevent premature labor, if necessary.

Prognosis
Many women who have fibroids have no symptoms or have only minor symptoms of heavy menstrual
bleeding or pelvic pressure. However, fibroids tend to
grow over time, and gradually cause more symptoms.
Many women ultimately decide to have some form of
treatment. Currently, hysterectomy is the most popular
form of treatment.

Prevention
Uterine fibroids cannot be prevented.
Resources
BOOKS

Friedman, Andrew J. ‘‘Uterine Fibroids.’’ In Primary
Care of Women, edited by Karen J. Carlson and
Stephanie A. Eisenstat. St. Louis: Mosby-Year
Book,Inc., 1995.

Amy B. Tuteur, MD

Uterus x rays see Hysterosalpingography

Uveitis
Definition
Uveitis is an inflammation of the uveal tract,
which lines the inside of the eye behind the cornea.
Much of the uvea lies between the retina and tough,
outer sclera. The uveal tract has three parts: the iris,
the ciliary body, and the choroid. Uveitis is categorized according to the part of the uveal tract that is
affected. Anterior uveitis is an inflammation of the
front part of the uveal tract; it includes inflammation
of the iris (iritis) and inflammation of the iris and the
ciliary body (iridocyclitis). Posterior uveitis is an
inflammation of the part of the uveal tract behind
the lens of the eye. It includes inflammation of the
choroid (choroiditis) and inflammation of the choroid
and retina (chorioretinitis). Uveitis that affects the
entire uveal tract is called panuveitis or diffuse uveitis.
GALE ENCYCLOPEDIA OF MEDICINE

The uveal tract is made up of the iris, ciliary
body, and choroid. The iris is the colored part of the
eye. The ciliary body is inside the eye and produces a
fluid called aqueous humor. Ciliary muscles aid in
accommodation, the process of changing the shape
of the lens in the eye to see things at various distances.
The choroid lines the back of the eye and has many
blood vessels. It helps nourish part of the retina.
The choroid lies between the retina and outermost
sclera.
Uveitis may either persist for a long time
(chronic) or have a short-term duration (acute).
Anterior uveitis is classified as either granulomatous
or nongranulomatous. The distinction is based on the
disease agents that were considered responsible for
the condition. At one time, it was thought that granulomatous uveitis was caused by tuberculosis bacilli
whereas nongranulomatous uveitis was thought to be
caused by streptococci. The distinction is still used
even though the causes of uveitis are now understood
differently.
In most cases, uveitis affects only one eye,
although posterior uveitis sometimes involves both
eyes. About 60% of cases develop within the eye
itself, but 40% are associated with systemic diseases
or disorders ranging from toxoplasmosis to syphilis.
Many of these are diseases of childhood and adolescence. Uveitis does not appear to run in families
or to be associated with lifestyle choices, occupational history, geographical location, or environmental factors.
Uveitis is a serious condition that may develop
rapidly and cause lasting damage to the eye. Patients
who think they may have chronic uveitis should seek
evaluation and treatment by an ophthalmologist
(a physician who specializes in diseases of the eye)
as soon as possible. If the patient has a sudden loss
of vision and the eye looks inflamed, the patient
should go immediately to the doctor for emergency
treatment.

Anterior uveitis
The so-called classic symptoms of anterior uveitis—
severe pain; redness, particularly around the edge of the
iris; and extreme sensitivity to light (photophobia)—
occur mostly in acute uveitis. In anterior uveitis, the
doctor will see a so-called ‘‘flare and cell’’ pattern
when looking into the watery fluid (aqueous humor)
between the cornea and the lens of the patient’s eye.
The iris may adhere to the lens, thus increasing the
intraocular pressure. There may be nodules on the
iris. There may be tearing and the pupil may be constricted and nonreactive. In severe cases of anterior
uveitis, there may be hypopyon (a small amount of
pus or collection of white cells) visible when the doctor
examines the eye.
GRANULOMATOUS UVEITIS. In granulomatous
uveitis, there will be large yellowish-white cells visible
on the back of the cornea, and possibly some small
nodules on the iris. Granulomatous uveitis is usually
less acute than the nongranulomatous form; the eye is
only mildly inflamed and the patient’s vision is somewhat blurred.

Granulomatous uveitis can be produced by
syphilis, toxoplasmosis, cytomegalovirus, sarcoidosis,
tuberculosis, or Vogt-Koyonagi-Harada syndrome
(VKH). VKH is marked by severe uveitis associated
with hair loss, hearing loss, loss of pigment in the
eyelashes and brows, and headaches. It occurs most
commonly in Asians.
NONGRANULOMATOUS UVEITIS. In nongranulomatous uveitis, the cells visible on the cornea are
smaller, and there are no masses on the iris. This type
of anterior uveitis is, however, more painful. The eye is
red and the patient experiences both photophobia and
loss of vision.

Systemic diseases that can cause nongranulomatous uveitis include ankylosing spondylitis, Reiter’s
syndrome, psoriasis, ulcerative colitis, Behcet’s syndrome, Lyme disease, and Crohn’s disease. Children—
especially girls—with anterior uveitis should be
screened for juvenile rheumatoid arthritis (JRA).

Causes and symptoms
The causes of uveitis are not fully understood, but
they can be a result of trauma, allergy, or a response to
a systemic or ocular disease. Uveitis may be a type of
immune-response mechanism. In people with impaired
immune systems, uveitis may be due to an infection.
Chronic uveitis is often associated with systemic
disorders (e.g., Lyme disease, sarcoidosis, or juvenile
rheumatoid arthritis).
GALE ENCYCLOPEDIA OF MEDICINE

Posterior uveitis
The symptoms of posterior uveitis are sometimes
subtle. The patient may notice blurred or hazy vision,
or floating black spots before the eyes. There may be
pain and photophobia. The iris may attach to the lens
in the eye thus increasing intraocular pressure.
Posterior uveitis may be acute or chronic. It is
more likely to involve both eyes. When the doctor
3871

Uveitis

Description

Uveitis

KEY TERMS
Choroid—The part of the uveal tract behind the
ciliary body. The choroid underlies and nourishes
the retina and absorbs scattered light.
Ciliary body—The part of the uveal tract between
the iris and the choroid.
Cornea—The transparent front part of the eye that
covers the iris and pupil.
Flare and cell—A pattern revealed by slit-lamp
examination that indicates uveitis. Flare and cell
resembles light filtered through smoke.
This person has acute iritis, or inflammation of the iris.
Symptoms include pain in the eye or forehead and reddening
of the margin of the iris. Treatment requires total rest of the
eye (dark glasses and atropine drops which paralyze the
muscles of accommodation), accompanied by application of
corticosteroids. (Photo Researchers, Inc. Reproduced by
permission.)

examines the eye, cells may be seen in the vitreous
humor, which is the normally transparent gel that
fills the eyeball behind the lens. There will be yellowish
or dark areas of inflammation on the choroid and the
retina. The blood vessels in the retina develop a sheath
or covering of inflammatory tissue. In severe cases, the
vitreous humor is so cloudy that the doctor cannot see
the retina at the back of the eye.
PARS PLANITIS. Pars planitis is an inflammation of
the pars plana, which is a part of the ciliary body. Pars
planitis usually occurs in older children or young
adults, and can develop into posterior uveitis.

The diseases that cause granulomatous uveitis
may also cause posterior uveitis.

Diagnosis
The eye doctor will examine the patient’s eyes with
a slit lamp in order to rule out conjunctivitis and
certain types of glaucoma. The slit lamp is an instrument that combines a binocular microscope with a
special light. The slit lamp can shine a narrow beam
of very bright light into the eye and allow the doctor to
examine the front part of the eye in detail. The slitlamp exam is not painful, however if the patient is
sensitive to light there will be discomfort.
The absence of a discharge from the eye and the
absence of infectious organisms in a laboratory smear
usually rule out conjunctivitis. In addition, the size of
the pupil is often small in uveitis whereas it is normal
in conjunctivitis. In acute glaucoma, the patient has
3872

Hypopyon—A small amount of pus or collection of
white cells that is visible in the front of the eye in
severe cases of anterior uveitis.
Iris—The circular membrane that forms the colored
portion of the eye and expands or contracts around
the pupil.
Photophobia—Extreme sensitivity to light.
Photophobia is a major symptom of acute uveitis.
Pupil—The opening in the center of the iris that
allows light to pass through to the retina.
Retina—The innermost membrane at the back of
the eyeball on which images are projected by the
lens.
Slit lamp—An instrument that combines a binocular microscope with special lights. It allows an eye
doctor to examine the front portion of the eye.
Uveal tract—The pigmented membrane that lines
the back of the retina of the eye and extends forward to include the iris. The uveal tract is sometimes called the uvea and has three parts: the iris,
the choroid, and the ciliary body.
Vitreous humor—The clear gel-like substance that
fills the eyeball behind the lens.

severe pain, the cornea of the eye is cloudy, and the
pressure level of the fluid inside the eye is abnormally
high; whereas in uveitis the pain is moderate, the cornea is clear, and the fluid pressure is normal or possibly lower or slightly above normal. The doctor may
also use the slit lamp and another lens to examine the
back of the eye to get a good look at the retina and
choroid. Other instruments, such as a hand-held
ophthalmoscope or a binocular indirect ophthalmoscope, can be used to examine the back of the eye.
There should be no discomfort with these tests except
if the patient is sensitive to the bright light.
GALE ENCYCLOPEDIA OF MEDICINE

Laboratory testing is used to rule out conjunctivitis in some patients. The doctor wipes the inside of the
patient’s eyelid with a swab in order to obtain a sample
for testing. Although blood tests are not necessary to
diagnose uveitis by itself, they are used to diagnose the
cause if the doctor suspects that toxoplasmosis or
another systemic disease is responsible for the uveitis.

Treatment
Uveitis is generally treated by an ophthalmologist
because therapy requires topical and oral medications,
however, some optometrists (O.D.) are state licensed
to use therapeutic medications. Other doctors may be
involved in treating the underlying disease, if the
patient has one, and in monitoring the patient’s
responses to medications.
Anterior uveitis is treated with corticosteroid drops;
in severe cases, the patient may be given steroid injections in the area of the eye or oral steroids. Atropine
sulfate drops may be given to dilate the patient’s pupil.
Posterior uveitis is treated with systemic corticosteroids.
It is usually not necessary to dilate the pupil.
Prolonged steroid use may increase intraocular
pressure, thereby increasing the risk of glaucoma.
Steroid use has also been connected to cataract formation. Patients should be monitored closely and
frequently.

GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
The prognosis depends upon the location of the
uveitis, on whether it is chronic or acute, and on the
promptness of treatment. The prognosis for untreated
uveitis is poor. Untreated anterior uveitis usually
progresses to posterior uveitis, resulting in cataracts,
scar tissue, and eventual glaucoma. If treated
promptly, anterior uveitis usually clears up in several
days or weeks, but is likely to recur. Posterior uveitis
usually results in some permanent loss or blurring of
vision.

Prevention
Patients with anterior uveitis should be warned
about the possibility of recurrence and instructed
about its symptoms, especially inflammation of the
iris. They should be advised to seek treatment at
once at the first signs of recurrence.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.

Rebecca J. Frey, PhD

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Laboratory testing

V
Vaccination
Definition
Vaccination is the use of vaccines to prevent specific diseases.

Purpose
Many diseases that once caused widespread illness, disability, and death now can be prevented
through the use of vaccines. Vaccines are medicines
that contain weakened or dead bacteria or viruses.
When a person takes a vaccine, his or her immune
system responds by producing antibodies—substances
that weaken or destroy disease-causing organisms.
When the person is later exposed to live bacteria or
viruses of the same kind that were in the vaccine, the
antibodies prevent those organisms from making the
person sick. Vaccines usually also stimulate
the so-called cellular immune system as well. In other
words, the person becomes immune to the disease the
organisms normally cause. The process of building up
immunity by taking a vaccine is called immunization.
Vaccines are used in several ways. Some, such as
the rabies vaccine, are given only when a person is
likely to have been exposed to the virus that causes
the disease—through a dog bite, for example. Others
are given to travelers planning to visit countries where
certain diseases are common such as typhoid fever or
yellow fever. Vaccines such as the influenza vaccine, or
‘‘flu shot,’’ are given mainly to specific groups of
people—older adults and others who are at high risk
of developing influenza or its complications. Then,
there are vaccines that are given to almost everyone,
such as the ones that prevent diphtheria, tetanus, polio
and measles.
Children routinely have a series of vaccinations
that begins at birth. Given according to a specific schedule, these vaccinations protect against hepatitis B,
GALE ENCYCLOPEDIA OF MEDICINE

diphtheria, tetanus, pertussis (whooping cough),
measles, mumps, rubella (German measles), varicella
(chickenpox), polio, pneumococcus and Haemophilus
influenzae type b (Hib disease, a major cause of spinal
meningitis) and, in some states, hepatitis A. This series
of vaccinations is recommended by the American
Academy of Family Physicians, the American
Academy of Pediatrics, and the Centers for Disease
Control and Prevention and is required in all states
before children can enter school. All states will make
exceptions for children who have medical conditions
such as cancer that prevent them from having vaccinations, and some states also will make exceptions for
children whose parents object for religious or other
reasons.

Description
In addition to those discussed above, vaccines are
available for preventing anthrax, cholera, hepatitis A,
Japanese encephalitis, meningococcal meningitis,
plague, pneumococcal infection (meningitis, pneumonia), tuberculosis, typhoid fever, and yellow fever. Most
vaccines are given as injections, but a few are given by
mouth.
Some vaccines are combined in one injection, such
as the measles-mumps-rubella (MMR) or diphtheriapertussis-tetanus (DPT) combinations.

Recommended dosage
The recommended dosage depends on the type of
vaccine and may be different for different patients.
The healthcare professional who gives the vaccine
will decide on the proper dose.
A vaccination health record will help parents and
health care providers keep track of a child’s vaccinations. The record should be started when the child has
his or her first vaccination and should be updated with
each additional vaccination. While most physicians
3875

Vaccination

ALBERT BRUCE SABIN
(1906-1993)
Albert Bruce Sabin was born on August 26, 1906, in
Bialystok, Russia, to Jacob and Tillie Sabin. In order to
escape extreme poverty, the Sabins immigrated to the
United States and settled in Paterson, New Jersey.
Following his graduation from high school in 1923,
Sabin was able to attend dentistry school at New York
University due to his uncle’s generous offer for financing.
However, after reading Paul deKruif’s Microbe Hunters
he became intrigued by virology and the idea of curing
epidemic diseases. After two years of dentistry school,
Sabin decided to switch to medicine, earning his M.D. in
1931. Sabin completed his residency and internship in
the United States and then went to London to conduct
research.
Sabin returned to the United States in 1935 to
resume his research of polio at the Rockefeller Institute.
In 1953, Jonas Salk announced that he had created a
dead-virus polio vaccine that was safe, but soon after its
administration many people died. Sabin, however,
wanted to create a live-virus vaccine, which he felt
would be safer. Sabin diluted three strains of the polio
virus and tested these on himself, his family, and other
volunteers. These live-virus vaccines (given orally)
proved safe and effective and soon became the vaccinations of choice around the world. Sabin’s published
works include Viruses and Cancer: A Public Lecture in
Conversational Style (1965), Behavior of ChimpanzeeAvirulent Poliomyelitis Viruses in Experimentally
Infected Human Volunteers (1955), and Recent
Advances in Our Knowledge of Dengue and Sand Fly
Fever (1955). Sabin died of congestive heart failure on
March 3, 1993.

follow the recommended vaccination schedule, parents should understand that some flexibility is
allowed. For example, vaccinations that are scheduled
for age two months may be given anytime between six
to 10 weeks. When possible, follow the schedule.
However, slight departures will not prevent the child
from developing immunity, as long as all the vaccinations are given at around the right times. The child’s
physician is the best person to decide when each vaccination should be given.
Anyone planning a trip to another country should
check to find out what vaccinations are needed. Some
vaccinations must be given as much as 12 weeks before
the trip, so getting this information early is important.
Many major hospitals and medical centers have travel
clinics that can provide this information. The
3876

Recommended Immunization Schedule

Age

Vaccine

0–2
months
1–4
months
2 months

Hepatitis B

4 months
6 months
6–18
months
12–15
months
12–18
months
15–18
months
4–6 years
11–12
years
11–16
years

Hepatitis B
DTP (diphtheria-tetanus-pertussis) Hib (Haemophilus
influenzae type B)Polio
DTPHibPolio
DTPHib
Hepatitis BPolio
HibMMR (measles-mumps-rubella)
Varicella (chickenpox)
DTP
DTPPolioMMR
Hepatitis B (if not already completed)MMR (if not already
completed)Varicella (if not already completed)
DT (diptheria-tetanus booster shot; and then booster shot
every 10 to 15 years)

Traveler’s Health Section of the Centers for Disease
Control and Prevention also has information on vaccination requirements.

Precautions
Vaccines are not always effective, and there is no
way to predict whether a vaccine will ‘‘take’’ in any
particular person. To be most effective, vaccination
programs depend on whole communities participating. The more people who are vaccinated, the lower
everyone’s risk of being exposed to a disease. Even
people who do not develop immunity through vaccination are safer when their friends, neighbors, children, and coworkers are immunized.
Like most medical procedures, vaccination has
risks as well as substantial benefits. Anyone who
takes a vaccine should make that sure he or she is
fully informed about both the benefits and the risks.
Any questions or concerns should be discussed with a
physician or other health care provider. The Centers
for Disease Control and Prevention, located in
Atlanta, Georgia, also is a good source of
information.
Vaccines may cause problems for people with certain allergies. For example, people who are allergic to
the antibiotics neomycin or polymyxin B should not
take rubella vaccine, measles vaccine, mumps vaccine
or the combined measles-mumps-rubella (MMR)
GALE ENCYCLOPEDIA OF MEDICINE

Vaccination

A.
Antigens

B
Macrophage
T

B

D.

B.

Antibody
T

T

C.
How vaccines work: A. Vaccines contain antigens (weakened or dead viruses, bacteria, and fungi that cause disease and
infection). When introduced into the body, the antigens stimulate the immune system response by instructing B cells to produce
antibodies, with assistance from T-cells. B. The antibodies are produced to fight the weakened or dead viruses in the vaccine. C.
The antibodies ‘‘practice’’ on the weakened viruses, preparing the immune system to destroy real and stronger viruses in the
future. D. When new antigens enter the body, white blood cells called macrophages engulf them, process the information
contained in the antigens, and send it to the T-cells so that an immune system response can be mobilized. (Illustration by
Electronic Illustrators Group.)

vaccine. Anyone who has had a severe allergic reaction
to baker’s yeast should not take the hepatitis B vaccine.
Patients who are allergic to antibiotics such as gentamicin sulfate, streptomycin sulfate or other aminoglycosides should check with their physicians before
taking influenza vaccine, as some influenza vaccines
contain small amounts of these drugs. Also, some
vaccines, including those for influenza, measles and
GALE ENCYCLOPEDIA OF MEDICINE

mumps, are grown in the fluids of chick embryos and
should not be taken by people who are allergic to
eggs. In general, anyone who has had an unusual reactions to a vaccine in the past should let his or her
physician know before taking the same kind of vaccine
again. The physician also should be told about any
allergies to foods, medicines, preservatives, or other
substances.
3877

Vaginal pain

may also develop a fever or a rash. In rare cases,
vaccines may cause severe allergic reactions, swelling
of the brain, or seizures. Anyone who has an unusual
reaction after receiving a vaccine should get in touch
with a physician right away.

Interactions
Vaccines may interact with other medicines and
medical treatments. When this happens, the effects of
the vaccine or the other medicine may change or the
risk of side effects may be greater. For example, radiation therapy and cancer drugs may reduce the effectiveness of many vaccines or may increase the chance
of side effects. Anyone who takes a vaccine should let
the physician know all other medicines he or she is
taking and should ask whether the possible interactions could interfere with the effects of the vaccine or
the other medicines.
Resources
An allergic reaction to a vaccination shot. (Photograph by
Lester V. Bergman, Corbis Images. Reproduced by permission.)

People with certain other medical conditions
should be cautious about taking vaccines. Influenza
vaccine, for example, may reactivate Guillain-Barré
syndrome (GBS) in people who have had it before.
This vaccine also may worsen illnesses that involve the
lungs, such as bronchitis or pneumonia. Vaccines that
cause fever as a side effect may trigger seizures in
people who have a history of seizures caused by fever.
Certain vaccines are not recommended for use
during pregnancy, but some may be given to women
at especially high risk of getting a specific disease such
as polio. Vaccines also may be given to pregnant
women to prevent medical problems in their babies.
For example, vaccinating a pregnant woman with
tetanus toxoid can prevent her baby from getting tetanus at birth.
Women should avoid becoming pregnant for
three months after taking rubella vaccine, measles
vaccine, mumps vaccine or the combined measlesmumps-rubella (MMR) as these vaccines could cause
problems in the unborn baby.
Women who are breastfeeding should check with
their physicians before taking any vaccine.

Side effects
Most side effects from vaccines are minor and
easily treated. The most common are pain, redness,
and swelling at the site of the injection. Some people
3878

OTHER

Centers for Disease Control National Immunization
Program. <http://www.cdc.gov/nip>.
National Immunization Information Hotline. Centers for
Disease Control and Prevention. (800) 232-2522.

Larry I. Lutwick, MD

Vaccines see Vaccination

Vaginal pain
Definition
Pain in the vaginal canal is usually associated with
an underlying medical and/or psychological condition.

Description
Vaginal pain is experienced usually during vaginal
manipulation or sexual intercourse. Approximately
50–85% of the causes are due to organic (medical) conditions. However, it is typical for the medical condition
to be compounded by psychological issues such as
depression and problems associated with sexual identity.
The primary entity concerns dyspareunia, a vaginal pain
experienced during sexual intercourse. The vagina has
three physiological functions: an outflow duct for menstrual discharge, to receive the penis during sexual intercourse, and as the birthing canal. The overall prevalence
for dyspareunia is 20% (15% of women and 57% of
GALE ENCYCLOPEDIA OF MEDICINE

Anthrax—An infectious disease caused by a type of
bacterium. The disease can be passed from animals
to people and usually is fatal. Symptoms include
sores on the skin.
Antibody—A type of protein produced in the blood or
in the body tissues that helps the body fight infection.
Bacteria—Tiny, one-celled forms of life that cause
many diseases and infections.
Cholera—An infection of the small intestine caused
by a type of bacterium. The disease is spread by
drinking water or eating seafood or other foods that
have been contaminated with the feces of infected
people. It occurs in parts of Asia, Africa, Latin
America, India, and the Middle East. Symptoms
include watery diarrhea and exhaustion.
Encephalitis—Inflammation of the brain, usually
caused by a virus. The inflammation may interfere
with normal brain function and may cause seizures,
sleepiness, confusion, personality changes, weakness
in one or more parts of the body, and even coma.
Feces—The solid waste that is left after food is
digested. Feces form in the intestines and pass out
of the body through the anus. Also called stool.
Guillain-Barré syndrome (GBS)—A disease of the
nerves with symptoms that include sudden numbness
and weakness in the arms and legs, sometimes leading
to paralysis. The disease is serious and requires medical treatment, but most people recover completely.
Immune system—The body’s natural defenses
against disease and infection.
Immunization—A process or procedure that protects
the body against an infectious disease. A vaccination
is a type of immunization.

men). A significant percentage of breast cancer and hysterectomy patients demonstrated sexual dysfunction.

Causes and symptoms
The causes can be categorized as organic, due to a
medical condition and/or psychological difficulties.
Medical conditions can include chronic diseases, minor
ailments, breast cancer, and medications. Psychological
cause can be related to physical or sexual abuse.
Pregnancy and hormonal changes (decreased estrogen)
have significant negative impact on sexual activity,
desire, and satisfaction. Dyspareunia can be divided
GALE ENCYCLOPEDIA OF MEDICINE

Inflammation—Pain, redness, swelling, and heat
that usually develop in response to injury or illness.
Meningitis—Inflammation of tissues that surround
the brain and spinal cord.
Microorganism—An organism that is too small to be
seen with the naked eye.
Organism—An individual of some type of life form,
such as a plant, an animal, or a microorganism.
Plague—A highly infectious disease that can be fatal
if not treated promptly. The bacteria that cause
plague mainly infect rats, mice, squirrels, and other
wild rodents. The disease is passed to people through
fleas. Infected people can then spread the disease to
other people.
Seizure—A sudden attack, spasm, or convulsion.
Tuberculosis—An infectious disease that usually
affects the lungs, but may also affect other parts of
the body. Symptoms include fever, weight loss, and
coughing up blood.
Typhoid fever—An infectious disease caused by a
type of bacterium. People with this disease have a
lingering fever and feel depressed and exhausted.
Diarrhea and rose-colored spots on the chest and
abdomen are other symptoms. The disease is spread
through poor sanitation.
Virus—A tiny, disease-causing particle that can
reproduce only in living cells.
Yellow fever—An infectious disease caused by a
virus. The disease, which is spread by mosquitoes,
is most common in Central and South America and
Central Africa. Symptoms include high fever, jaundice (yellow eyes and skin) and dark-colored vomit,
a sign of internal bleeding. Yellow fever can be fatal.

into three types of pain: superficial, vaginal, and deep.
Superficial pain is associated with attempted penetration. This is usually caused by changes in anatomy,
irritative condition, or vaginismus. Vaginal pain is associated with friction, indicating a problem with lubrication and /or arousal disorders. Deep pain is related to
thrusting and is indicative of pelvic disease or an inability
for pelvic relaxation.

Diagnosis
The diagnosis must be pursued with diligence and
in a comprehensive manner. A careful history and
3879

Vaginal pain

KEY TERMS

Vagotomy

Purpose

KEY TERMS
Laparoscopic surgery—A surgical procedure to
correct or diagnose an underlying disease.

physical examination is essential. Procedures that can
be used include surgical investigation (laparoscopy)
and treatment of the underlying cause(s).

Treatment
Treatment is directed at diagnosing the underlying condition, which can be medical and/or psychological cause(s). Treatment can include surgery,
hormonal therapy (replacements), psychotherapy,
and pain control protocols.

Prognosis
The prognosis depends on the primary cause. If
treatment is aggressively pursued and patient compliance is satisfactory the overall outcome is favorable.

Prevention
There are no precise preventive measures since the
condition can result from normal aging and/or progressively worsening psychological disease.
Resources
BOOKS

Goroll, Allan H., et al. Primary Care Medicine. 4th ed.
Lippincott, Williams & Wilkins, 2000.
Ryan, Kenneth J., et al, editors. Kistner’s Gynecology &
Women’s Health. 7th ed. Mosby, Inc., 1999.

Laith Farid Gulli, M.D.
Kathleen Berrisford, MSW, CSW

Vaginal warts see Genital warts
Vaginitis see Vulvovaginitis

Vagotomy
Definition
Vagotomy is the surgical cutting of the vagus
nerve to reduce acid secretion in the stomach.
3880

The vagus nerve splits into branches that go to
different parts of the stomach. Stimulation from these
branches causes the stomach to produce acid. Too
much stomach acid leads to ulcers that may eventually
bleed and create an emergency situation.
Vagotomy is performed when acid production in
the stomach can not be reduced by other means. It is
used when ulcers in the stomach and duodenum do not
respond to medication and changes in diet. It is an
appropriate surgery when there are ulcer complications, such as obstruction of digestive flow, bleeding,
or perforation. The frequency with which elective
vagotomy is performed has decreased in the past 20
years as drugs have become increasingly effective in
treating ulcers. However, the number of vagotomies
performed in emergency situations has remained
about the same.
Vagotomy is often performed in conjunction with
other gastrointestinal surgery, such as partial removal
of the stomach (antrectomy or subtotal gastrectomy).
There are several types of vagotomies. Truncal vagotomy severs the trunk of the vagus nerve as it enters the
abdomen. Parietal cell or proximal gastric vagotomy
leaves the trunk intact, but severs the branches that go
to different parts of the stomach.

Precautions
Patients who receive vagotomies are most often
seen in emergency situations where bleeding and perforated ulcers make it necessary to act immediately. As
with any major surgery, people who use alcohol excessively, smoke, are obese, and are very young or very
old are at higher risks for complications.

Description
Vagotomy is performed under general anesthesia by a surgeon in a hospital. The surgeon makes
an incision in the abdomen and locates the vagus
nerve. Either the trunk or the branches leading to
the stomach are cut. Then the abdominal muscles
are sewn back together, and the skin is closed with
sutures.
Often, other gastrointestinal surgery is performed
at the same time as the vagotomy. Part of the stomach
may be removed, for instance. Vagotomy causes a
decrease in peristalsis and a change in the emptying
patterns of the stomach. To ease this, a pyloroplasty is
often performed. This procedure widens the outlet
from the stomach to the small intestine.
GALE ENCYCLOPEDIA OF MEDICINE

Duodenum—The section of the small intestine
immediately after the stomach.
Peristalsis—The rhythmic contractions that move
material through the bowel.

BOOKS

Way, Lawrence W., editor. ‘‘Stomach and Duodenum.’’ In
Current Surgical Diagnosis and Treatment. 10th ed.
Stamford: Appleton & Lange, 1994.

Tish Davidson, A.M.

Valacyclovir see Antiviral drugs
Preparation
A gastroscopy and x rays of the gastrointestinal
system are performed as diagnostic procedures to
determine the position and condition of the ulcer.
Standard preoperative blood and urine tests are
done. The patient should discuss with the anesthesiologist any medications or conditions that might affect
the administration of anesthesia.

Aftercare
Patients who have had a vagotomy stay in the
hospital for about seven days. For the first three or
four days, nasogastric suctioning is required. A tube is
inserted through the nose and into the stomach. The
stomach contents are then suctioned out. Patients eat
a clear liquid diet until the gastrointestinal tract is
functioning again. When patients return to a regular
diet, spicy and acidic food should be avoided.
It takes about six weeks to fully recover from the
surgery. The sutures that close the skin can be
removed in seven to ten days. Patients are encouraged
to move around soon after the operation to prevent
the formation of deep vein blood clots. Pain medication, stool softeners, and antibiotics may be prescribed
following the operation.

Risks
As with all surgery, excessive bleeding and infection are possible complications. In addition, the emptying patterns of the stomach are changed. This can
lead to dumping syndrome and diarrhea. Dumping
syndrome is a condition where shortly after eating,
the patient experiences palpitations, sweating, nausea,
cramps, vomiting, and diarrhea.

Normal results
Normal recovery is expected for most patients. In
about 10% of those who have vagotomy without stomach removal, ulcers recur. Two to three percent of
patients who have some portion of their stomach
removed also have recurrent ulcers.
GALE ENCYCLOPEDIA OF MEDICINE

Valley fever see Coccidioidomycosis

Valsalva maneuver
Definition
The Valsalva maneuver is performed by attempting to forcibly exhale while keeping the mouth and
nose closed. It is used as a diagnostic tool to evaluate
the condition of the heart and is sometimes done as a
treatment to correct abnormal heart rhythms or
relieve chest pain.

Purpose
The Valsalva maneuver is used with patients who
have suspected heart abnormalities, often in conjunction with echocardiography. The maneuver is based on
the fact that when a patient forcibly exhales against a
closed nose and mouth while bearing down, as if having a bowel movement, specific changes occur in blood
pressure and the rate and volume of blood returning to
the heart.
Comparing the changes in a diseased heart to
those expected in a normal heart gives clues to the
type and location of heart damage. In addition, when
a doctor listens to the chest with a stethoscope during
the Valsalva maneuver, characteristic heart sounds are
heard. Variations in these sounds can indicate the type
of abnormality present in the heart. A 2004 study
found that blood pressure response to the Valsalva
maneuver could predict mortality in elderly patients
with congestive heart failure. This could prove to be a
new noninvasive way to help determine how long
elderly patients with congestive heart failure are
expected to live.
The Valsalva maneuver also corrects some rapid
heartbeats originating in the atria. When the maneuver is done correctly, blood pressure rises. This forces
the heart to respond by correcting its rhythm and
beating more slowly. On rare occasions, the Valsalva
3881

Valsalva maneuver

Resources

KEY TERMS

Valvular heart disease

Risks

KEY TERMS
Atria—The heart has four chambers. The right and
left atria are at the top of the heart and receive
returning blood from the veins. The right and left
ventricles are at the bottom of the heart and act as
the body’s main pumps.
Echocardiography—An ultrasound test that shows
the size, shape, and movement of the heart.

The patient may feel dizzy or faint during the
procedure, but serious consequences are rare. There
is a risk that the Valsalva maneuver can cause blood
clots to detach, bleeding, and abnormal rhythms originating in the ventricle. It can also cause cardiac
arrest. Consequently, the procedure is usually performed in a setting where emergency equipment is
accessible.

Normal results
maneuver can be used to diminish chest pain in
patients with mild coronary disease.
Unrelated to any evaluation of the heart, the
Valsalva maneuver also is taught to patients with multiple sclerosis who are unable to fully empty the bladder (flaccid bladder). It sometimes is used in sexual
therapy to help men avoid premature ejaculation.

There are four characteristic changes or phases in
a normal heart’s response to the Valsalva maneuver.
An abnormality in any of these phases indicates a
cardiovascular abnormality.
Resources
PERIODICALS

Jancin, Bruce. ‘‘New Mortality Predictor Found for Heart
Failure.’’ Family Practice News March 15, 2004: 48–49.

Tish Davidson, A.M.
Teresa G. Odle

Precautions
The Valsalva maneuver should not be performed
by patients who have severe coronary artery disease,
have experienced recent heart attack, or have a moderate to severe reduction in blood volume.

Valvular heart disease

Description
When performed formally, the patient is asked to
blow against an aneroid pressure measuring device
(manometer) and maintain a pressure of 40 millimeters of mercury (mm Hg) for 30 seconds. Or, less
formally, the patient may be asked to bear down, as if
having a bowel movement. During this 30 second
period, a recording is made of the changes in blood
pressure and murmurs of the heart.

Preparation
The patient may be connected to a heart monitor
and echocardiograph or the physician may simply use
a stethoscope to monitor the heart. Sometimes an
indwelling needle is inserted for accurate pressure
measurements, depending on whether the procedure
is being done for corrective or diagnostic purposes.

Definition
Valvular heart disease refers to several disorders
and diseases of the heart valves, which are the tissue
flaps that regulate the flow of blood through the chambers of the heart.

Description
The human heart consists of four chambers—two
upper chambers (the atria) and two lower chambers
(the ventricles) that are responsible for pumping
blood. The heart valves are like one-way doors,
which open and close with each beat of the heart,
controlling the blood flow from one chamber to the
next. Each of these valves is made up of a few thin
folds of tissue. When functioning correctly, they keep
blood from flowing backward into a chamber when
closed.

Aftercare
When this procedure is done to regulate irregular
heart rhythms, the patient usually remains on a heart
monitor to evaluate heartbeat.
3882

The four valves function in the following manner:


The mitral valve is located between the left atrium
and the left ventricle. It is the only valve with two
flaps, or cusps.
GALE ENCYCLOPEDIA OF MEDICINE

The tricuspid valve is located on the right side of the
heart, between the right atrium and right ventricle. It
is made up of three cusps, each a different size.



The aortic valve is located on the left side of the heart
and opens to allow blood to leave the heart from the
left ventricle into the aorta, which is the main artery
of the body. It closes to prevent blood from flowing
back into the left ventricle.



The pulmonary valve is situated on the right side of
the heart, between the right ventricle and pulmonary
artery. It allows blood to exit the heart and enter the
lungs via the pulmonary artery. It closes to prevent
blood from flowing back into the right ventricle.

Patients with valvular heart disease have a malfunction of one or more of these valves. There are
several types of valvular heart diseases with distinct
symptoms and treatments. These are:


mitral valve prolapse (displacement)



mitral valve insufficiency (regurgitation)



mitral valve stenosis (narrowing)



aortic valve insufficiency



aortic valve stenosis



tricuspid valve insufficiency



tricuspid valve stenosis



pulmonic stenosis



pulmonic insufficiency

Certain types of heart disease can lead to one of
the specific conditions listed above. These include
rheumatic fever and infective inflammation of the
heart (endocarditis). Multivalvular heart disease refers
to a condition involving more than one of the heart
valves.

Causes and symptoms
Problems with heart valves may occur as a result
of infection, degeneration, or congenital abnormality.
The most common infections are rheumatic fever and
infective endocarditis.
Rheumatic fever
Rheumatic fever is a condition that results from
the body’s immune response to certain types of streptococcal bacteria. It occurs rarely. When it occurs, it is
most often in children who have had strep throat that
was not completely treated. The symptoms of rheumatic fever include heart inflammation, uncontrolled
movement of face and limbs, arthritis that moves from
joint to joint, shortness of breath, weakness, and either
GALE ENCYCLOPEDIA OF MEDICINE

lumps under the skin or raised red patches on the skin.
The most common valvular heart diseases to result
from rheumatic fever are mitral stenosis, tricuspid
stenosis, aortic insufficiency, aortic stenosis, multivalvular involvement, and less commonly, pulmonic
stenosis. Chronic rheumatic heart disease can result
from one occurrence or from repeated attacks. It is not
as common as it once was in the United States, but still
occurs frequently in developing countries.
Infective endocarditis
Infective endocarditis is an infection and inflammation of the inner layer, or membrane, of heart tissue
(endocardium). Most people with a healthy, normal
heart are not at significant risk for contracting infective endocarditis. However, people who have had
rheumatic fever, with its resulting scarring, or a congenital cause of heart malformation, may contract this
disease when certain bacteria enter the bloodstream
and become lodged in the heart. In particular, dental
surgery or any surgery involving the mouth, bladder,
prostate, or female pelvic organs increases risk for this
infection. The disease also may occur in drug addicts
who inject their veins using unsterilized needles, even if
they have normal heart valves. Symptoms of infective
endocarditis include fever, a new or changing heart
murmur, and abnormal loss of appetite or fatigue.
The use of appetite suppressants
In 1997 the manufacturers of fen-phen, the abbreviation for a combination of the two weight-loss drugs
fenfluramine and phentermine, withdrew the supplements from the market. Preliminary research showed
that they caused heart valve problems in some
patients. Physicians were concerned that this drug
combination could affect the heart valves because the
drugs alter metabolism of serotonin in the body.
Serotonin is a natural substance found in the brain
and intestines that can affect blood vessels. Until the
issue could be studied more, physicians recommended
that patients taper off the drugs, finally stopping them
altogether. Eventually, the company reached a $3.75
billion settlement of most lawsuits by former users of
the diet drugs.
Other valvular heart disease
The mitral and aortic valves may also be affected
by deposits of calcium in the heart that occurs with
aging. This can lead to thickening and leakage of heart
valves. Heart attacks also can damage the mitral valve
structures. Additionally, certain connective tissue disorders can adversely affect the heart valves, for
3883

Valvular heart disease



Valvular heart disease

example, Marfan’s syndrome and myxomatous
degeneration.

Diagnosis
Specific types of valvular heart disease are diagnosed using electrocardiography (EKG), echocardiography, certain x-ray studies, and/or cardiac
catheterization. An EKG provides a record of electrical changes in the heart muscle during the heartbeat.
Echocardiography uses sound waves to make images
of the heart. These images can show if there are any
abnormalities of the heart valves. Cardiac catheterization is a procedure in which a small tube (called a
catheter) is inserted into an artery and passed into
the heart. It is used to measure pressure in the heart
and the amount of blood pumped by the heart.
Rheumatic fever
Rheumatic fever may be suspected when a recent
throat infection has occurred and other major or
minor symptoms appear, such as joint ache, abnormal
EKG, or a blood test indicating heart inflammation.
Heart murmurs may be detected from routine
examination.
Infective endocarditis
A diagnosis of infective endocarditis can be
obtained through patient history, EKG, ultrasound,
or cardiac catheterization. Patients who have developed the disease rapidly may report fever, fatigue,
night sweats, chills, and joint inflammation. Those
whose disease has developed more slowly will show
signs of rapid heart rate, an enlarged spleen, various
skin colors or spots, and heart murmur. The physician
may order blood tests to determine what is causing the
infection.
Appetite suppressants
People with a history of using appetite suppressants may be sent for EKGs or further testing if any of
the symptoms of valvular heart disease, such as swelling, considerable fatigue, or shortness of breath
occur.

Treatment
The treatment of specific valvular heart diseases
will vary, depending on the valve involved and the
extent of damage or malfunction. Some patients will
not require treatment and many will be treated with
medication. Sometimes, patients need surgery. If
3884

multivalvular disease is suspected or involved, different valves may be evaluated during surgery on one of
the affected valves. Women with heart valve disease
who want to become pregnant should receive a thorough check-up and see a cardiologist regularly
throughout their pregnancy.
Rheumatic fever
Patients with rheumatic fever will be treated with
antibiotics to eliminate streptococcal organisms that
may still remain in the heart. Patients may receive
antibiotics to prevent further infection, and inflammation may be treated with aspirin or cortisone-like
drugs.
Infective endocarditis
Physicians will use the appropriate antibiotic or
some combination of antibiotics to treat infective
endocarditis, depending on the type of bacterium
that caused the disease. Severe cases of this disease
may be corrected by valve replacement surgery.
Appetite suppressants
The role of appetite suppressants (fen-phen) in
valvular heart disease has been under study. Many
of the people who suffered complications of the
diet drugs experienced regurgitation. However,
some 2001 studies found that these valve problems
often did not worsen or even improved after a
period of time after the patients stopped taking
fen-phen.

Prognosis
The prognosis for patients with valvular heart
disease varies depending on the underlying cause, age
and health of the patient, and the degree of valvular
damage or involvement.
Rheumatic fever
Patients with rheumatic heart disease face a lifetime of caution over contact with the same bacterium
that caused the disease. Since it can cause inflammation of one or more organs or joints, complications
can occur. The inflammation of the heart may subside
without side effects. Permanent scarring of one or
more heart valves is a possibility and may require
surgery to repair or replace damaged valves. In severe
cases, rheumatic fever can lead to death from heart
failure.
GALE ENCYCLOPEDIA OF MEDICINE

Valvular heart disease

Left common carotid artery

Left subclavian artery

Brachiocephalic trunk
Superior vena cava

Aorta
Right
pulmonary
artery

Trunk of left pulmonary artery

Right
pulmonary
veins

Left pulmonary veins
Left atrium

Semilunar valve
Semilunar valve
Atrioventricular valve
Left ventricle
Atrioventricular valve
Septum

Right ventricle

Apex of heart
Inferior vena cava
Oxygen-rich blood
from the lungs
Oxygen-poor blood
from the upper part
of the body

oxygen-poor blood
from the lower part
of the body

ventricles
relaxed

Oxygen-rich blood
to the body
Oxygen-poor
blood to the lungs

ventricles
contracted

Anatomy of the human heart. The illustration at the bottom right shows how the right and left ventricles contract and relax when
blood is pumped through the heart. (Illustration by Hans & Cassady, Inc.)

Infective endocarditis
The prognosis for patients with infective endocarditis depends on the underlying heart disease and
resulting complications. If the disease further

GALE ENCYCLOPEDIA OF MEDICINE

damages heart valves, symptoms may occur for
years after initial treatment. Sometimes, endocarditis
can result in heart or renal failure. If untreated, it can
be fatal.
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Varicose veins

Appetite suppressants

KEY TERMS
Congenital—Used to describe a condition or defect
present at birth.
Stenosis—An abnormal valve condition which is
characterized by tightening or narrowing of the
opening.
Streptococcal (Streptococcus)—Streptococcus is a
bacterium that causes infection in people. Its most
commonly known strain causes the infection strep
throat.
Throat culture—A test for strep throat that involves
swabbing the back of the throat and sending the
swab to a laboratory, which will determine
whether bacteria is present.

The drug associated with valvular heart disease,
fen-phen, was removed from the market, so as long as
people avoid obtaining this appetite suppression combination, they can prevent its negative effects.
Resources
PERIODICALS

Ball, Deborah, and James Kanter. ‘‘European Court
Overturns Ban on a Class of Drugs on Obesity.’’ Wall
Street Journal January 29, 2003: A2.
Moskowitz, Daniel B. ‘‘The Skinny on Diet Drug
Settlement.’’ Business & Health October 2000: 23.
Reimold, Sharon C., and John D. Rutherford. ‘‘Valvular
Heart Disease in Pregnancy.’’ The New England Journal
of Medicine July 3, 2003: 52–58.
‘‘What Happened After Patients Stopped Taking FenPhen?’’ Heart Disease Weekly March 11, 2001: 8.
ORGANIZATIONS

Appetite suppressants
Since it is believed that different valves may be
affected, treatment for those taking these drugs most
likely follows a similar course as that for the specific
valvular disease.

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Teresa G. Odle

Prevention
Certain measures can be taken to prevent some
valvular disease. However, once valvular heart disease
that results from congenital abnormality occurs, it
may not be prevented. Steps can be taken to prevent
further complications.

Valvuloplasty see Heart valve repair
Varicella see Chickenpox
Varicocele removal see Testicular surgery

Rheumatic fever
The best prevention for rheumatic fever is prompt
and thorough treatment of any suspected streptococcal infection, particularly strep throat in children. A
physician should check any sore throat with fever that
persists for more than 24 hours. The physician will
probably order a throat culture. Completion of the
antibiotic treatment even after symptoms diminish is
important to be certain the infection is eliminated.
Infective endocarditis
Anyone who was born with a defective heart
valve, those with artificial (prosthetic) valves, or
those who have had a valve scarred by rheumatic
fever, should use prescribed antibiotics by mouth
before and after a dental procedure. These patients
also may need to receive injected antibiotics prior to
procedures involving the bladder, prostate, and pelvic
organs.
3886

Varicose veins
Definition
Varicose veins are dilated, tortuous, elongated
superficial veins that are usually seen in the legs.

Description
Varicose veins, also called varicosities, are seen most
often in the legs, although they can be found in other
parts of the body. Most often, they appear as lumpy,
winding vessels just below the surface of the skin. There
are three types of veins, superficial veins that are just
beneath the surface of the skin, deep veins that are large
blood vessels found deep inside muscles, and perforator
veins that connect the superficial veins to the deep veins.
GALE ENCYCLOPEDIA OF MEDICINE

The inside wall of veins have valves that open and
close in response to the blood flow. When the left ventricle of the heart pushes blood out into the aorta, it
produces the high pressure pulse of the heartbeat and
pushes blood throughout the body. Between heartbeats,
there is a period of low blood pressure. During the low
pressure period, blood in the veins is affected by gravity
and wants to flow downward. The valves in the veins
prevent this from happening. Varicose veins start when
one or more valves fail to close. The blood pressure in that
section of vein increases, causing additional valves to fail.
This allows blood to pool and stretch the veins, further
weakening the walls of the veins. The walls of the affected
veins lose their elasticity in response to increased blood
pressure. As the vessels weaken, more and more valves
are unable to close properly. The veins become larger and
wider over time and begin to appear as lumpy, winding
chains underneath the skin. Varicose veins can develop in
the deep veins also. Varicose veins in the superficial veins
are called primary varicosities, while varicose veins in the
deep veins are called secondary varicosities.

Varicose veins

The superficial veins are the blood vessels most often
affected by varicose veins and are the veins seen by eye
when the varicose condition has developed.

Varicose veins on a man’s leg. (Custom Medical Stock Photo.
Reproduced by permission.)

KEY TERMS

Causes and symptoms
The predisposing causes of varicose veins are multiple, and lifestyle and hormonal factors play a role.
Some families seem to have a higher incidence of
varicose veins, indicating that there may be a genetic
component to this disease. Varicose veins are progressive; as one section of the veins weakens, it causes
increased pressure on adjacent sections of veins.
These sections often develop varicosities. Varicose
veins can appear following pregnancy, thrombophlebitis, congenital blood vessel weakness, or obesity, but is
not limited to these conditions. Edema of the surrounding tissue, ankles, and calves, is not usually a
complication of primary (superficial) varicose veins
and, when seen, usually indicates that the deep veins
may have varicosities or clots.
Varicose veins are a common problem; approximately 15% of the adult population in the United
States have varicose veins. Women have a much
higher incidence of this disease than men. The symptoms can include aching, pain, itchiness, or burning
sensations, especially when standing. In some cases,
with chronically bad veins, there may be a brownish
discoloration of the skin or ulcers (open sores) near the
ankles. A condition that is frequently associated with
varicose veins is spider-burst veins. Spider-burst veins
are very small veins that are enlarged. They may be
GALE ENCYCLOPEDIA OF MEDICINE

Congenital—Existing at or before birth; a condition
that developed while the fetus was in utero or as a
consequence of the birth process.
Edema—Swelling caused by a collection of fluid in
a tissue or body cavity.
Hemorrhage—Bleeding from blood vessels.
Palpation—The process of examining a patient by
touch.

caused by back-pressure from varicose veins, but can
be caused by other factors. They are frequently associated with pregnancy and there may be hormonal
factors associated with their development. They are
primarily of cosmetic concern and do not present any
medical concerns.

Diagnosis
Varicose veins can usually be seen. In cases where
varicose veins are suspected, but can not be seen, a
physician may frequently detect them by palpation
(pressing with the fingers). X rays or ultrasound tests
can detect varicose veins in the deep and perforator
veins and rule out blood clots in the deep veins.
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Varicose veins

Small saphenous vein
Figure A
Perforating veins
Great saphenous vein

Figure B

First incision

Second incision

Small end of
the vein stripper

Figure C

Large end of
the vein stripper
Vein

Varicose veins may be surgically removed from the body when they are causing pain and when hemorrhaging or recurrent
thrombosis appear. Surgery involves making an incision through the skin at both ends of the section of vein being removed
(figure B). A flexible wire is inserted through one end and extended to the other. The wire is then withdrawn, pulling the vein out
with it (figure C). (Illustration by Electronic Illustrators Group.)

Treatment
There is no cure for varicose veins. Treatment falls
into two classes; relief of symptoms and removal of the
affected veins. Symptom relief includes such measures
as wearing support stockings, which compress the
veins and hold them in place. This keeps the veins
from stretching and limits pain. Other measures are
sitting down, using a footstool when sitting, avoiding
standing for long periods of time, and raising the legs
whenever possible. These measures work by reducing
the blood pressure in leg veins. Prolonged standing
allows the blood to collect under high pressure in the
varicose veins. Exercise such as walking, biking, and
swimming, is beneficial. When the legs are active, the
leg muscles help pump the blood in the veins. This
limits the amount of blood that collects in the varicose
veins and reduces some of the symptoms. These measures reduce symptoms, but do not stop the disease.
Surgery is used to remove varicose veins from the
body. It is recommended for varicose veins that are
3888

causing pain or are very unsightly, and when hemorrhaging or recurrent thrombosis appear. Surgery
involves making an incision through the skin at both
ends of the section of vein being removed. A flexible
wire is inserted through one end and extended to the
other. The wire is then withdrawn, pulling the vein out
with it. This is called ‘‘stripping’’ and is the most
common method to remove superficial varicose
veins. As long as the deeper veins are still functioning
properly, a person can live without some of the superficial veins. Because of this, stripped varicose veins are
not replaced.
Injection therapy is an alternate therapy used to
seal varicose veins. This prevents blood from entering
the sealed sections of the vein. The veins remain in the
body, but no longer carry blood. This procedure can
be performed on an out-patient basis and does not
require anesthesia. It is frequently used if people
develop more varicose veins after surgery to remove
the larger varicose veins and to seal spider-burst veins
for people concerned about cosmetic appearance.
GALE ENCYCLOPEDIA OF MEDICINE

Prognosis
Untreated varicose veins become increasingly
large and more obvious with time. Surgical stripping
of varicose veins is successful for most patients. Most
do not develop new, large varicose veins following
surgery. Surgery does not decrease a person’s tendency
to develop varicose veins. Varicose veins may develop
in other locations after stripping.
Resources

Antibodies are immune cells which recognize and
bind to specific markers (called antigens) on other cells
(including bacteria and viruses). These antibody-antigen complexes can then stimulate the immune system
to send a variety of other cells and chemicals involved
in inflammation to their specific location.
Some researchers believe that the damaging process of vasculitis is kicked off by such antibody-antigen complexes. These complexes are deposited along
the walls of the blood vessels. The resulting inflow of
immune cells and chemicals causes inflammation
within the blood vessels.
The type of disease caused by vasculitis varies
depending on a number of factors:


the organ system or tissue in which the vasculitis
occurs



the specific type of inflammatory response provoked



whether the affected vessels are veins (which bring
blood to the heart) or arteries (which carry blood and
oxygen from the heart to the organs and tissues)



the degree to which blood flow within the affected
vessel is reduced

BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, editors. The
Heart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD

Variola see Smallpox
Vascular headache see Migraine headache

Causes and symptoms

Vasculitis
Definition
Vasculitis refers to a varied group of disorders
which all share a common underlying problem of
inflammation of a blood vessel or blood vessels. The
inflammation may affect any size blood vessel, anywhere in the body. It may affect either arteries and/or
veins. The inflammation may be focal, meaning that it
affects a single location within a vessel; or it may be
widespread, with areas of inflammation scattered
throughout a particular organ or tissue, or even affecting more than one organ system in the body.

Description
Inflammation is a process which occurs when the
immune system of the body responds to either an
injury or a foreign invader (virus, bacteria, or fungi).
The immune system response involves sending a variety of cells and chemicals to the area in question.
Inflammation causes blood vessels in the area to
leak, causing swelling. The inflamed area becomes
red, hot to the touch, and tender.
GALE ENCYCLOPEDIA OF MEDICINE

Some types of vasculitis appear to be due to a type
of allergic response to a specific substance (for example, a drug). Other types of vasculitis have no identifiable initiating event. Furthermore, researchers have
not been able to consistently identify antibody-antigen
complexes in all of the types of diseases caused by
vasculitis. The types of antigens responsible for the
initial immune response have often gone unidentified
as well. Furthermore, not all people with such complexes deposited along the blood vessels go on to
develop vasculitis. Some researchers believe that, in
addition to the presence of immune complexes, an
individual must have some other characteristics
which make him or her susceptible to vasculitis.
Many questions have yet to be answered to totally
explain the development these diseases.
Symptoms
Symptoms of vasculitis depend on the severity of
the inflammation and the organ system or systems
affected. Some types of vasculitis are so mild that the
only symptoms noted are small reddish-purple dots
(called petechiae) on the skin due to tiny amounts of
blood seeping out of leaky blood vessels. In more
widespread types of vasculitis, the patient may have
general symptoms of illness, including fever, achy
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Vasculitis

Injection therapy is also called sclerotherapy. At one
time, a method of injection therapy was used that did
not have a good success rate. Veins did not seal properly and blood clots formed. Modern injection therapy
is improved and has a much higher success rate.

Vasculitis

muscles and joints, decreased appetite, weight loss,
and loss of energy. The organ systems affected by
vasculitis may include:


The skin. Rashes, bumps under the skin, petechiae,
larger reddish-purple circles (purpura), or bruising
(ecchymoses) may appear. Areas of skin totally
deprived of blood flow, and therefore of oxygen,
may die, resulting in blackened areas of gangrene.



The joints. In addition to joint pain, the joints themselves may become inflamed, resulting in arthritis.



Brain and nervous system. Inflammation of the
blood vessels in the brain can cause headaches,
changes in personality, confusion, and seizures. If
an area of the brain becomes totally deprived of
oxygen, a stroke occurs. A stroke means that an
area of brain tissue is either severely injured or completely dead from lack of oxygen. This may leave the
individual with a permanent disability. If the vessels
that lead to the eyes are affected, vision may become
seriously disturbed. Nerves in the arms and legs may
result in painful tingling sensations, loss of feeling,
and weakness.



Gastrointestinal system. Patients may have significant abdominal pain, vomiting, and diarrhea. If
blood flow is completely cut off to an area of intestine, that part of the intestine will die off. The liver
may be affected.



Heart. This is an extremely serious type of vasculitis.
The arteries of the heart (coronary arteries) may
develop weakened areas, called aneurysms. The
heart muscle itself may become inflamed and
enlarged. With oxygen deprivation of the heart muscle, the individual may suffer a heart attack.





This person’s legs are afflicted with leukocytoblastic vasculitis, a condition in which a blood or lymph vessel becomes
inflamed. (Custom Medical Stock Photo. Reproduced by
permission.)

Lungs. The patient may experience shortness of
breath with chest pain, and may cough up blood.
There may be wheezing.

involved, and the inflammation is so severe that the
walls of the arteries may be destroyed. Any organ
system, or multiple organ systems, may be affected.
The most serious effects include kidney failure, complications involving the heart, gastrointestinal problems, and high blood pressure.

Kidney. Changes in the arteries of the kidney may
result in high blood pressure. The kidneys may
become increasingly unable to appropriately filter
the blood, and kidney failure may occur.


Kawasaki’s disease is an acute disease which primarily strikes young children. Fever and skin manifestations occur in all patients. While most patients
recover completely, a few patients suffer from vasculitis in the heart. This is frequently fatal.



Henoch-Schonlein purpura. While this frequently
occurs in children, adults may also be affected. This
disease tends to affect the skin, joints, gastrointestinal tract, and kidneys.



Serum sickness occurs when an individual reacts to a
component of a drug, for example penicillin.

Specific diseases
Multiple types of disease are associated with vasculitis. Many autoimmune diseases have vasculitis as
one of their complications. These include systemic
lupus erythematosus, rheumatoid arthritis, scleroderma,
and polymyositis. Other types of diseases which have
vasculitis as their major manifestations include:


Polyarteritis nodosa. This is an extremely serious,
systemic (affecting systems throughout the body)
form of vasculitis. Small and medium arteries are

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GALE ENCYCLOPEDIA OF MEDICINE

Takayasu’s arteritis affects the aorta (the very large
main artery that exits the heart and receives all of the
blood to be delivered throughout the body), and
arteries which branch off of the aorta. Initial symptoms include fatigue, fever, sweating at night, joint
pain, and loss of appetite and weight. Every organ
may be affected by this disease. A common sign of
this disease is the inability to feel the pulse in any of
the usual locations (the pulse is the regular, rhythmic
sensation one can feel with a finger over an artery, for
example in the wrist, which represents the beating of
the heart and the regular flow of blood).

Aneurysm—A weakened area in the wall of a blood
vessel which causes an outpouching or bulge.
Aneurysms may be fatal if these weak areas burst,
resulting in uncontrollable bleeding.
Antibody—Specialized cells of the immune system which can recognize organisms that invade
the body (such as bacteria, viruses, and fungi).
The antibodies are then able to set off a complex chain of events designed to kill these foreign invaders.
Antigen—A special, identifying marker on the outside of cells.



Wegener’s granulomatosis: This disease exerts its
most serious effects on the respiratory tract. The
vasculitis produced by this disease includes the formation of fibrous, scarring nodules called granulomas. Symptoms include nose bleeds, ear infections,
cough, shortness of breath, and chest pain. There
may be bleeding in the lungs, and a patient may
cough up blood. The kidneys, eyes, and skin are
also frequently involved.

Autoimmune disorder—A disorder in which the
body’s antibodies mistake the body’s own tissues for foreign invaders. The immune system
therefore attacks and causes damage to these
tissues.
Immune system—The system of specialized
organs, lymph nodes, and blood cells throughout
the body which work together to prevent foreign
invaders (bacteria, viruses, fungi, etc.) from taking
hold and growing.
Inflammation—The body’s response to tissue
damage. Includes hotness, swelling, redness, and
pain in the affected part.
Petechia—A tiny, purplish-red spot on the skin.
Caused by the leakage of a bit of blood out of a
vessel and under the skin.
Purpura—A large, purplish-red circle on the skin.
Caused by the leakage of blood out of a vessel and
under the skin.

Symptoms of this are often confined to the skin,
although fevers, joint pain, and swelling of lymph
nodes may also occur.


Temporal arteritis (also called giant cell arteritis)
tends to involve arteries which branch off the
major artery that leads to the head, called the carotid. An artery which feeds tissues in the area of the
temple (the temporal artery) is often affected.
Severe headaches are the most classic symptom.
Other symptoms include fatigue, loss of appetite
and then weight, fever, heavy sweating, joint pain,
and pain in the muscles of the neck, shoulders, and
back. If the vasculitis includes arteries which supply
the eye, serious visual disturbance or even blindness
may result.

GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Diagnosis of any type of vasculitis involves
demonstrating the presence of a strong inflammatory
process. Tests which reveal inflammation throughout
the body include erythrocyte sedimentation rate, blood
tests which may reveal anemia and increased white
blood cells, and tests to demonstrate the presence of
immune complexes and/or antibodies circulating in
the blood. An x-ray procedure, called angiography,
involves injecting dye into a major artery, and then
taking x-ray pictures to examine the blood vessels,
in order to demonstrate the presence of inflammation
of the vessel walls. Tissue samples (biopsies) may
be taken from affected organs to demonstrate
inflammation.

Treatment
Even though there are many different types of
vasculitis, with many different symptoms based on
the organ system affected, treatments are essentially the same. They all involve trying to decrease
the activity of the immune system. Steroid medications (like prednisone) are usually the first types of
drugs used. Steroids work by interfering with the
chemicals involved in the inflammatory process.
More potent drugs for severe cases of vasculitis
have more serious side effects. These include
drugs like cyclophosphamide. Cyclophosphamide
works by actually killing cells of the patient’s
immune system.
3891

Vasculitis



KEY TERMS

Vasectomy

Prognosis
The prognosis for vasculitis is quite variable.
Some mild forms of vasculitis, such as those brought
on by reactions to medications, may resolve totally
on their own and not even require treatment.
Temporal arteritis, serum sickness, HenochSchonlein purpura, and Kawasaki’s disease usually
have excellent prognoses, although when Kawasaki’s
affects the heart, there is a high death rate. Other
types of vasculitis were always fatal, prior to the
availability of prednisone and cyclophosphamide,
and continue to have high rates of fatal complications. These include polyarteritis nodosa and
Wegener’s granulomatosis.

Prevention
Because so little is known about what causes a
particular individual to develop vasculitis, there are
no known ways to prevent it.
Resources
ORGANIZATIONS

Lupus Foundation of America. 1300 Piccard Dr., Suite 200,
Rockville, MD 20850. (800) 558-0121. <http://
www.lupus.org>.
Wegener’s Foundation, Inc. 3705 South George Mason
Drive, Suite 1813 South, Falls Church, VA 22041. (703)
931-5852.

Rosalyn Carson-DeWitt, MD

effectiveness is 99.6%. Vasectomy is the most reliable
method of contraception.

Description
Vasectomies are often performed in the doctor’s
office using a local anesthesia. The patient’s scrotum
area will be shaved and cleaned with an antiseptic
solution to reduce the chance of infection. A small
incision is made into the scrotum (the sac containing
the testicles that produce the sperm). Each of the vas
deferens (one from each testicle) is tied in two places
with nonabsorbable (permanent) sutures and the tube
is severed between the ties. The ends may be cauterized
(burned or seared) to decrease the chance that they will
leak or grow back together.
Sterility does not occur immediately after the procedure is finished. Men must use other methods of
contraception until two consecutive semen analyses
confirm that there are no sperm present in the semen.
This will take four to six weeks or 15-20 ejaculations to
clear all of the sperm from the tubes.
‘‘No scalpel’’ vasectomies are gaining popularity.
Instead of an incision, a small puncture is made into
the scrotum. The vas deferens are cut and sealed in a
manner similar to that described above. No stitches are
necessary and the patient has less pain. Other advantages include less damage to the tissues, less bleeding, less
risk of infection, and less discomfort after the procedure.
In some, cases vasectomies may be reversed.
However, this procedure should be considered permanent as there is no guarantee of successful reversal.

Preparation

Vasectomy
Definition
A vasectomy is a surgical procedure performed on
males in which the vas deferens (tubes that carry sperm
from the testicles to the seminal vesicles) are cut, tied,
cauterized (burned or seared) or otherwise interrupted. The semen no longer contains sperm after the
tubes are cut, so conception cannot occur. The testicles
continue to produce sperm, but they die and are
absorbed by the body.

Purpose
The purpose of this operation is to provide reliable contraception. Research indicates that the level of
3892

No special physical preparation is required. The
physician will first assess the patient’s general health in
order to identify any potential problems that could
occur. The doctor will then explain possible risks and
side effects. The patient is asked to sign a consent form
which indicates that he understands the information
he has received, and gives the doctor permission to
perform the operation.

Aftercare
Following the surgery, ice packs are often applied
to scrotum to decrease pain and swelling. A dressing
(or athletic supporter) which supports the scrotum can
also reduce pain. Mild over-the-counter pain medication such as aspirin or acetaminophen (Tylenol) should
be able to control any discomfort. Activities may be
GALE ENCYCLOPEDIA OF MEDICINE

Risks

Prostate
gland

Vas deferens
(severed)

Urethra

Testis

Vasectomy is a surgical procedure performed on males in
which the vas deferens (tubes that conduct sperm from the
testicles to the penis) are cut, tied, cauterized, or otherwise
interrupted. Although the testicles still produce sperm, the
sperm die and are absorbed by the body. Men who have had
vasectomies may continue to ejaculate the same amount of
semen as before the procedure. (Illustration by Electronic
Illustrators Group.)

There are very few risks associated with vasectomy other than infection, bruising, epididymitis
(inflammation of the tube that carries the sperm
from the testicle to the penis), and sperm granulomas
(collection of fluid that leaks from a poorly sealed or
tied vas deferens). These are easily treated if they do
occur. Patients do not experience difficulty achieving
an erection, maintaining an erection, or ejaculating.
There is no decrease in the production of the male
hormone (testosterone), and sex drive and ability are
not altered. Vasectomy is safer and less expensive than
tubal ligation (sterilization of a female by cutting the
fallopian tube to prevent conception).

Normal results
Normally, vasectomies are 99% successful in preventing conception. As such, it is one of the most
effective methods available to consumers.
Resources
ORGANIZATIONS

Planned Parenthood Federation of America, Inc.. 810
Seventh Ave., New York, NY 10019. (800) 669-0156.
<http://www.plannedparenthood.org>.

Donald G. Barstow, RN

KEY TERMS
Ejaculation—The act of expelling the sperm
through the penis during orgasm.
Epididymitis—Inflammation of the small tube that
rests on top of the testicle and is part of the system
that carries sperm from the testicle to the penis. The
condition can be successfully treated with antibiotics if necessary.
Scrotum—The sac which contains the testicles.
Sperm granuloma—A collection of fluid that leaks
from an improperly sealed or tied vas deferens.
They usually disappear on their own, but can be
drained if necessary.
Testicles—The two egg-shaped organs found in the
scrotum that produce sperm.
Tubal ligation—A surgical procedure in which the
fallopian tubes are tied in two places and cut
between. This prevents eggs from moving from
the ovary to the uterus.

GALE ENCYCLOPEDIA OF MEDICINE

Vasodilators
Definition
Vasodilators are medicines that act directly on
muscles in blood vessel walls to make blood vessels
widen (dilate).

Purpose
Vasodilators are used to treat high blood pressure
(hypertension). By widening the arteries, these drugs
allow blood to flow through more easily, reducing
blood pressure. Controlling high blood pressure is
important because the condition puts a burden on
the heart and the arteries, which can lead to permanent
damage over time. If untreated, high blood pressure
increases the risk of heart attack, heart failure, stroke,
3893

Vasodilators

restricted for one or two days, and sexual intercourse
for three to four days.

Bladder

Vasodilators

or kidney failure. Vasodilators usually are prescribed
with other types of blood pressure drugs and rarely are
used alone.

Description
Examples of vasodilators are hydralazine
(Apresoline) and minoxidil (Loniten). The vasodilator
hydralazine also may be used to control high blood
pressure in pregnant women or to bring down extremely high blood pressure in emergency situations. In
the forms used for treating high blood pressure
(tablets or injections), these drugs are available only
with a physician’s prescription. A liquid form of minoxidil, used to promote hair growth in people with
certain kinds of baldness and is applied directly to
the scalp, and is sold without a prescription.

Recommended dosage
The recommended dosage depends on the type of
vasodilator. The physician who prescribed the drug or
the pharmacist who filled the prescription can recommend the correct dosage. This medicine should only be
used as directed.
Physicians usually prescribe vasodilators along
with other blood pressure medicines. Taking each
drug at the correct time is extremely important.
Health care providers can offer suggestions on how
to remember when to take each drug.

Precautions
Seeing a physician regularly while taking a vasodilator is important, especially during the first few
months. The physician will check to make sure the
medicine is working as it should and will watch for
unwanted side effects. People who have high blood
pressure often feel fine. But even when they feel well,
patients should keep seeing their physicians and taking
their medicine.
Vasodilators will not cure high blood pressure,
but will help control the condition. To avoid the serious health problems that high blood pressure can
cause, patients may have to take medicine for the rest
of their lives. Furthermore, medicine alone may not be
enough. People with high blood pressure also may
need to avoid certain foods and keep their weight
under control. The health care professional who is
treating the condition can offer advice on what measures may be necessary.
Some people feel dizzy or have headaches while
using this medicine. These problems are especially
3894

likely to occur in older people, who are more sensitive
than younger people to the medicine’s effects. Anyone
who takes these drugs should not drive, use machines,
or do anything else that might be dangerous until they
know how the drugs affect them.
Special conditions
People who have certain medical conditions or
who are taking certain other medicines may have
problems if they take vasodilators. In the past,
patients with severe aortic stenosis could not use
vasodilators because they could cause blood pressure
to drop too low and result in severe complications.
However, in 2003, a report announced that the vasodilator nitroprusside was safe in these patients and
rapidly improved their cardiac function. Before a
patient takes vasodilators, he or she should be sure
to let the physician know about any of these
conditions:
ALLERGIES. Anyone who has had an unusual
reaction to a vasodilator in the past should let his
or her physician know before taking this type of drug
again. The physician also should be told about any
allergies to foods, dyes, preservatives, or other
substances.
PREGNANCY. Several problems—from excess hair
growth to blood abnormalities—have been reported in
babies whose mothers take certain vasodilators during
pregnancy. In studies of laboratory animals, hydralazine caused birth defects in mice and rabbits, but not in
rats. The effects of taking vasodilators during pregnancy have not been specifically studied in humans.
Women who are pregnant or who may become pregnant should check with their physicians before using
this medicine. Women who become pregnant while
taking a vasodilator should tell their physicians right
away.
BREASTFEEDING. Women who are breastfeeding
their babies or who plan to breastfeed should
check with their physicians before using this
medicine.
OTHER MEDICAL CONDITIONS. Using a vasodilator to lower blood pressure may worsen the problems
that result from heart disease, blood vessel disease, or
a recent heart attack or stroke. This medicine also may
make angina (chest pain) worse. Vasodilators may
make pheochromocytomas (tumors of the adrenal
medulla), more active. Before using a vasodilator,
people with any of these medical problems should
make sure their physicians are aware of their
conditions.

GALE ENCYCLOPEDIA OF MEDICINE

USE OF CERTAIN MEDICINES. Taking vasodilators
with certain other drugs may affect the way the drugs
work or may increase the chance of side effects. Any
other prescription or nonprescription (over-the-counter) medicine should not be taken along with a vasodilator unless it has been discussed with the physician
who prescribed the vasodilator.

Side effects
Some side effects of vasodilators go away as the
body adjusts to the drug and do not need medical
attention unless they continue or interfere with normal
activities. These include:


headache



nausea or vomiting



diarrhea



loss of appetite

In addition, minoxidil may cause a temporary
increase in hair growth, especially on the face, arms,
and back. Patients who are bothered by this should
check with their physicians.
Other side effects of vasodilators should have
medical attention. Rapid or irregular heartbeat are
reasons to check with a physician immediately. And
if any of the following problems occur, a physician
should be consulted as soon as possible:


chest pain



muscle pain



joint pain



pain, numbness, tingling or weakness in the hands or
feet

KEY TERMS
Adrenal gland—One of a pair of organs located
next to the kidneys. The adrenal glands produce
hormones that control many body functions.
Adrenal medulla—The inner part of the adrenal
gland. The adrenal medulla produces the hormones epinephrine (adrenaline), which stimulates
the heart, tightens blood vessels, and relaxes some
smooth muscles; and norepinephrine, which has
similar effects.
Arteries—Blood vessels that carry blood away from
the heart to the cells, tissues, and organs of the body.

Additional side effects are possible. Anyone who
has unusual symptoms while taking a vasodilator
should get in touch with his or her physician.

Interactions
Vasodilators may interact with other medicines.
When this happens, the effects of one or both of the
drugs may change or the chance of side effects may be
greater. In addition, many prescription and nonprescription (over-the-counter) drugs may affect blood
pressure. No other medication should be taken without
the approval of the physician who prescribed the vasodilator. In particular, avoiding over-the-counter medicines for appetite control, colds, cough, sinus
problems, asthma, hay fever and other allergies,
should be avoided as these may increase blood pressure. At the other extreme, dangerously low blood
pressure may result when drugs such as the blood
pressure medicine guanethidine (Ismelin) or nitrates,
used to treat chest pain, are combined with
vasodilators.
Resources
PERIODICALS

Moon, Mary Ann. ‘‘Vasodilators Can Help, Not Hurt.’’
Internal Medicine News June 1, 2003: 40-41.



swollen feet or lower legs



swollen lymph nodes



bloating



fever and sore throat



general discomfort or feeling of illness

Vasodilatory see Shock



weakness



blisters on skin; skin rash or itching; flushing or redness of the skin

Vasopressin test see Antidiuretic hormone
(ADH) test

GALE ENCYCLOPEDIA OF MEDICINE

Nancy Ross-Flanigan
Teresa G. Odle

Vasovagal faint see Fainting
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Vasodilators

People with kidney disease also should check
with their physicians before using a vasodilator.
Side effects may be greater in these people because
their kidneys are slow to clear the medicine from
the body.

Vegetarianism

Vegetarianism
Definition
Vegetarianism is the voluntary abstinence from
eating meat. Vegetarians refrain from eating meat for
various reasons, including religious, health, and ethical ones. Lacto-ovo vegetarians supplement their diet
with dairy (lactose) products and eggs (ovo). Vegans
(pronounced vee-guns) do not eat any animal-derived
products at all.

Purpose
Vegetarianism is recommended as a dietary therapy for a variety of conditions, including heart disease,
high cholesterol, type 2 diabetes, and stroke.
Vegetarianism is a major dietary therapy in the alternative treatment of cancer. Other conditions treated
with a dietary therapy of vegetarianism include obesity, osteoporosis, arthritis, allergies, asthma, environmental illness, hypertension, gout, gallstones,
hemorrhoids, kidney stones, ulcers, colitis, premenstrual syndrome, anxiety, and depression. Vegetarians
often report higher energy levels, better digestion, and
mental clarity. Vegetarianism is an economical and
easily implemented preventative practice as well.

Description
The term vegetarian was coined in 1847 by the
founders of the Vegetarian Society of Great Britain,
but vegetarianism has been around as long as people
have created diets. Some of the world’s oldest cultures
advocate a vegetarian diet for health and religious
purposes. In India, millions of Hindus are vegetarians
because of their religious beliefs. One of the ancient
mythological works of Hinduism, the Mahabharata,
states that, ‘‘Those who desire to possess good memory, beauty, long life with perfect health, and physical,
moral and spiritual strength, should abstain from animal foods.’’ The yoga system of living and health is
vegetarian, because its dietary practices are based on
the belief that healthy food contains prana. Prana is
the universal life energy, which yoga experts believe is
abundant in fresh fruits, grains, nuts and vegetables,
but absent in meat because meat has been killed. Yogis
also believe that spiritual health is influenced by
the practice of ahimsa, or not harming living beings.
The principle of ahimsa (non-violence) appears in the
Upanishads (Vedic literature) from c. 600–300 B.C.
Taking of animal life or human life under any circumstances is sinful and results in rebirth as a lower organism. It became a fundamental element of Jainism,
3896

another religion of India. Some Buddhists in Japan
and China are also vegetarian because of spiritual
beliefs. In the Christian tradition, the Trappist
Monks of the Catholic Church are vegetarian, and
some vegetarians argue that there is evidence that
Jesus and his early followers were vegetarian. Other
traditional cultures, such as those in the Middle East
and the Mediterranean regions, have evolved diets
that frequently consist of vegetarian foods. The
Mediterranean diet, which a Harvard study declared
to be one of the world’s healthiest, is primarily,
although not strictly, vegetarian.
The list of famous vegetarians forms an illustrious
group. The ancient Greek philosophers, including
Socrates, Plato, and Pythagoras, advocated vegetarianism. In modern times, the word to describe someone who likes to feast on food and wine is ‘‘epicure,’’
but it is little known that Epicurus, the ancient philosopher, was himself a diligent vegetarian. Other
famous vegetarians include Leonardo da Vinci, Sir
Isaac Newton, Leo Tolstoy, Ralph Waldo Emerson,
and Henry Thoreau. This century’s celebrated vegetarians include Gandhi, the physician Albert
Schweitzer, writer George Bernard Shaw, musician
Paul McCartney, and champion triathlete Dave
Scott. Albert Einstein, although not a strict vegetarian
himself, stated that a vegetarian diet would be an
evolutionary step for the human race.
Vegetarianism in America received a lot of interest
during the last half of the nineteenth century and the
beginning of the twentieth century, during periods of
experimentation with diets and health practices.
Vegetarianism has also been a religious practice for
some Americans, including the Seventh-day
Adventists, whose lacto-ovo vegetarian diets have
been studied for their health benefits. Vegetarianism
has been steadily gaining acceptance as an alternative
to the meat-and-potatoes bias of the traditional
American diet. In 1997, Vegetarian Resource Group
performed a Roper poll that showed that 13 million
Americans, or 5% of the population, identified themselves as vegetarians.
Several factors contribute to the interest in vegetarianism in America. Outbreaks of food poisoning
from meat products, as well as increased concern over
the additives in meat such as hormones and antibiotics,
have led some people and professionals to question
meat’s safety. There is also an increased awareness of
the questionable treatment of farm animals in factory
farming. But the growing health consciousness of
Americans is probably the major reason for the surge
in interest in vegetarianism. Nutrition experts have built
up convincing evidence that there are major problems
GALE ENCYCLOPEDIA OF MEDICINE

He attended Bellevue Hospital Medical College in New
York where he received his medical degree in 1875. In
1876, at the age of 24, Kellogg became an abdominal
surgeon and superintendent of the Western Health
Reform Institute, which he renamed the Battle Creek
Sanitarium. There, he began applying his theories about
natural living to his medical practice. Himself a vegetarian,
he first advocated a diet high in whole grains, fruits, nuts,
and legumes. He later included all types of vegetables in
the diet. His controversial health regimen included morning calisthenics, open-air sleeping, cleansing enemas,
chewing food hundreds of times before swallowing, and
drinking plenty of water.

(AP/Wide World Photos. Reproduced by permission.)

John Harvey Kellogg is known as the father of modern
breakfast cereal. He was born in Tyrone Township,
Michigan, on February 26, 1852, into a Seventh Day
Adventist family. At age 12, he became an apprentice at
the Review and Herald Press, a publishing company run by
the church. He attended school in Battle Creek, Michigan.

with the conventional American diet, which is centered
around meat products that are high in cholesterol and
saturated fat and low in fiber. Heart disease, cancer, and
diabetes, which cause 68% of all deaths in America, are
all believed to be influenced by this diet. Nutritionists
have repeatedly shown in studies that a healthy diet
consists of plenty of fresh vegetables and fruits, complex
carbohydrates such as whole grains, and foods that are
high in fiber and low in cholesterol and saturated fat.
Vegetarianism, a diet that fulfills all these criteria, has
become part of many healthy lifestyles. In alternative
medicine, vegetarianism is a cornerstone dietary therapy, used in Ayurvedic medicine, detoxification treatments, macrobiotics, the Ornish diet for heart disease,
and in therapies for many chronic conditions.

Preparations
Some people, particularly those with severe or
chronic conditions such as heart disease or cancer,
GALE ENCYCLOPEDIA OF MEDICINE

In the 1890s, Kellogg established a laboratory at the
sanitarium to develop more nutritious foods. His brother,
Will Keith Kellogg, joined in his research. In 1895 they
developed a breakfast cereal of wheat flakes called
Granose. The cereal quickly grew in popularity and was
soon sold by mail order. This was followed by rice flakes
and corn flakes. The brothers established the Sanitas Food
Company. But philosophical differences led them to split
into two companies. Will founded the W. K. Kellogg
Company, which retained the rights to the cereal products.
John set up the Battle Creek Food Company, which produced coffee substitutes and soymilk. John Kellogg also
edited Good Health Magazine, which promoted vegetarianism, for 60 years. In 1904, he published a book, The Miracle
of Life. He continued to promote his version of healthy living
and radical techniques until his death in 1943.

may be advised by a health practitioner to become
vegetarian suddenly. For most people, nutritionists
recommend that a vegetarian diet be adopted gradually, to allow people’s bodies and lifestyles time to
adjust to new eating habits and food intake.
Some nutritionists have designed transition diets
to help people become vegetarian in stages. Many
Americans eat meat products at nearly every meal,
and the first stage of a transition diet is to substitute
just a few meals a week with wholly vegetarian foods.
Then, particular meat products can be slowly reduced
and eliminated from the diet and replaced with vegetarian foods. Red meat can be reduced and then eliminated, followed by pork, poultry, and fish. For those
wishing to become pure vegetarians or vegans, the
final step would be to substitute eggs and dairy products with other nutrient-rich foods. Individuals
should be willing to experiment with transition diets,
and should have patience when learning how combine
vegetarianism with social activities such as dining out.
3897

Vegetarianism

D R . J O H N H A R V E Y K E L L O G G (1852–1943)

Vegetarianism

The transition to vegetarianism can be smoother
for those who make informed choices with dietary
practices. Sound nutritional guidelines include
decreasing the intake of fat, increasing fiber, and
emphasizing fresh fruits, vegetables, legumes, and
whole grains in the diet while avoiding processed
foods and sugar. Everyone can improve their health
by becoming familiar with recommended dietary and
nutritional practices, such as reading labels and understanding basic nutritional concepts such as daily
requirements for calories, protein, fat, and nutrients.
Would-be vegetarians can experiment with meat substitutes, foods that are high in protein and essential
nutrients. Thanks to the growing interest in vegetarianism, many meat substitutes are now readily available. Tofu and tempeh are products made from
soybeans that are high in protein, calcium, and other
nutrients. There are ‘‘veggie-burgers’’ that can be
grilled like hamburgers, and vegetarian substitutes
for turkey and sausage with surprisingly authentic
textures and taste. There are many vegetarian cookbooks on the market as well.
A set of guidelines for North American vegetarian
diets, updated for 2004, is available from the
American Dietetic Association and the Dietitians of
Canada. The new guidelines are intended to promote
variety within vegetarian diets and to meet the needs of
different stages in the life cycle as well as incorporate
the most recent findings of medical research.
One remaining drawback to the widespread practice of vegetarianism is the unpleasant taste or smell of
many vegetables. A number of phytonutrients have a
bitter, astringent, or acrid taste that they impart to
products made from vegetables that contain them.
Some experts think that people tend to reject such
strong-smelling or bitter-tasting vegetables as turnips,
cabbage, brussels sprouts, or broccoli because humans
have been programmed in the course of evolution to
associate bitter taste with poisonous plants. It is
increasingly recognized that the major barrier to dietary change for the sake of health is taste. One recommendation for improving the taste appeal of
vegetarian diets is more frequent use of spices. In
addition to pleasing the human palate, spices derived
from plants have been shown to have chemoprotective
effects, boosting the immune system, reducing inflammation, and fighting harmful bacteria and viruses.

Precautions
In general, a well-planned vegetarian diet is
healthful and safe; in the summer of 2003, a position
paper endorsed by the American Dietetic Association
3898

and the Dietitians of Canada referred to vegetarian
diets as ‘‘healthful, nutritionally adequate, and [able
to] provide health benefits in the prevention and treatment of certain diseases.’’ However, vegetarians, and
particularly vegans who eat no animal products, need
to be aware of particular nutrients that may be lacking
in non-animal diets. These are amino acids, vitamin
B12, vitamin D, calcium, iron, zinc, and essential fatty
acids. Furthermore, pregnant women, growing children, and those with health conditions have higher
requirements for these nutrients.
Vegetarians should be aware of getting complete
protein in their diets. A complete protein contains all
of the essential amino acids, which are the building
blocks for protein essential to the diet because the
body cannot make them. Meat and dairy products
generally contain complete proteins, but most vegetarian foods such as grains and legumes contain
incomplete proteins, lacking one or more of the
essential amino acids. However, vegetarians can
easily overcome this by combining particular foods
in order to create complete proteins. For instance,
beans are high in the amino acid lysine but low in
tryptophan and methionine, but rice is low in lysine
and high in tryptophan and methionine. Thus, combining rice and beans makes a complete protein. In
general, combining legumes such as soy, lentils,
beans, and peas with grains like rice, wheat, or oats
forms complete proteins. Eating dairy products or
nuts with grains also makes proteins complete.
Oatmeal with milk on it is complete, as is peanut
butter on whole wheat bread. Proteins do not necessarily need to be combined in the same meal, but
generally within four hours.
Getting enough vitamin B12 may be an issue for
some vegetarians, particularly vegans, because meat
and dairy products are the main sources. Vitamin
supplements that contain vitamin B12 are recommended. Spirulina, a nutritional supplement made
from algae, is also a vegetarian source, as are fortified
soy products and nutritional yeast.
Vitamin D can be obtained by vitamins, fortified
foods, and sunshine. Calcium can be obtained in
enriched tofu, seeds, nuts, legumes, dairy products,
and dark green vegetables including broccoli, kale, spinach, and collard greens. Iron is found in raisins,
figs, legumes, tofu, whole grains (particularly whole
wheat), potatoes, and dark green leafy vegetables.
Iron is absorbed more efficiently by the body when
iron-containing foods are eaten with foods that contain vitamin C, such as fruits, tomatoes, and green
vegetables. Zinc is abundant in nuts, pumpkin seeds,
legumes, whole grains, and tofu. For vegetarians who
GALE ENCYCLOPEDIA OF MEDICINE

Vegetarians do not necessarily have healthier
diets. Some studies have shown that some vegetarians
consume large amounts of cholesterol and saturated
fat. Eggs and dairy products contain cholesterol and
saturated fat, while nuts, oils, and avocados are vegetable sources of saturated fat. To reap the full benefits
of a vegetarian diet, vegetarians should be conscious
of cholesterol and saturated fat intake. Vegetarians
may also consider buying organic foods, which are
grown without the use of synthetic chemicals, as
another health precaution.

Research and general acceptance
A vegetarian diet has many well-documented
health benefits. It has been shown that vegetarians
have a higher life expectancy, as much as several
years, than those who eat a meat-centered diet. The
U.S. Food and Drug Administration (FDA) has stated that data has shown vegetarians to have a strong or
significant probability against contracting obesity,
heart disease, lung cancer, colon cancer, alcoholism,
hypertension, diabetes, gallstones, gout, kidney stones,
and ulcers. However, the FDA also points out that
vegetarians tend to have healthy lifestyle habits, so
other factors may contribute to their increased health
besides diet alone.
A vegetarian diet, as prescribed by Dr. Dean
Ornish, has been shown to improve heart disease and
reverse the effects of atherosclerosis, or hardening of
the arteries. It should be noted that Dr. Ornish’s diet
was used in conjunction with exercise, stress reduction,
and other holistic methods. The Ornish diet is lactoovo vegetarian, because it allows the use of egg whites
and non-fat dairy products.
Vegetarians have a resource of statistics in their
favor when it comes to presenting persuasive arguments in favor of their eating habits. Vegetarians
claim that a vegetarian diet is a major step in improving the health of citizens and the environment.
Americans eat over 200 lbs (91 kg) of meat per person
per year. The incidence of heart disease, cancer diabetes, and other diseases has increased along with a
dramatic increase in meat consumption during the
past century. Many statistics show significantly smaller risks for vegetarians contracting certain conditions. The risks of women getting breast cancer and
men contracting prostrate cancer are nearly four
times as high for frequent meat eaters as for those
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Cholesterol—A steroid fat found in animal foods
that is also produced in the body from saturated fat
for several important functions. Excess cholesterol
intake is linked to many diseases.
Complex carbohydrates—Complex carbohydrates
are broken down by the body into simple sugars for
energy, are found in grains, fruits and vegetables.
They are generally recommended in the diet over
refined sugar and honey, because they are a more
steady source of energy and often contain fiber and
nutrients as well.
Legume—Group of plant foods including beans,
peas, and lentils, which are high in protein, fiber,
and other nutrients.
Organic food—Food grown without the use of synthetic pesticides and fertilizers.
Saturated fat—Fat that is usually solid at room
temperature, found mainly in meat and dairy products but also in vegetable sources such as some
nuts, seeds, and avocados.
Tempeh—A fermented cake of soybeans and other
grains; it is a staple food in Indonesia.
Tofu—A soft cheeselike food made from curdled
soybean milk.
Unsaturated fat—Fat found in plant foods that is
typically liquid (oil) at room temperature. They can
be monounsaturated or polyunsaturated, depending on the chemical structure. Unsaturated fats are
the most recommended dietary fats.

who eat meat sparingly or not at all. For heart
attacks, American men have a 50% risk of having
one, but the risk drops down to 15% for lacto-ovo
vegetarians and to only 4% for vegans. For cancer,
studies of populations around the world have implied
that plant-based diets have lower associated risks for
certain types of cancer.
Vegetarians claim other reasons for adopting a
meat-free diet. One major concern is the amount of
pesticides and synthetic additives such as hormones
that show up in meat products. Chemicals tend to
accumulate in the tissue of animals that are higher
in the food chain, a process called bioaccumulation.
Vegetarians, by not eating meat, can avoid the
exposure to these accumulated toxins, many of
which are known to influence the development of
3899

Vegetarianism

do not eat fish, getting enough omega-3 essential fatty
acids may be an issue, and supplements such as flaxseed
oil should be considered, as well as eating walnuts and
canola oil.

Vegetarianism

cancer. One study showed that DDT, a cancercausing pesticide, was present in significant levels
in mother’s milk for 99% of American women, but
only 8% of vegetarian women had significant levels
of the pesticide. Women who eat meat had 35
times higher levels of particular pesticides than
vegetarian women. The synthetic hormones and
antibiotics added to American cattle has led some
European countries to ban American beef altogether. The widespread use of antibiotics in livestock has made many infectious agents more
resistant to them, making some diseases harder to
treat.
Vegetarians resort to ethical and environmental
arguments as well when supporting their food
choices. Much of U.S. agriculture is dedicated to
producing meat, which is an expensive and
resource-depleting practice. It has been estimated
that 1.3 billion people could be fed with the grain
that America uses to feed livestock, and starvation is
a major problem in world health. Producing meat
places a heavy burden on natural resources, as compared to growing grain and vegetables. One acre of
land can grow approximately 40,000 lbs (18,000 kg)
of potatoes or 250 lbs (113 kg) of beef, and it takes
50,000 gal (200,000 l) of water to produce 1 lb (0.45
kg) of California beef but only 25 gal (100 l) of water
to produce 1 lb (0.45 kg) of wheat. Half of all water
used in America is for livestock production.
Vegetarians argue that the American consumption
of beef may also be contributing to global warming,
by the large amounts of fossil fuels used in its production. The South American rainforest is being cleared
to support American’s beef consumption, as the
United States yearly imports 300 million lbs (136 million kg) of meat from Central and South America.
The production of meat has been estimated as causing up to 85% of the loss of topsoil of America’s
farmlands. A German researcher in the field of nutrition ecology hs summarized the environmental benefits of vegetarian diets: ‘‘Research shows that
vegetarian diets are well suited to protect the environment, to reduce pollution, and to minimize global
climate changes.’’
Despite the favorable statistics, vegetarianism
does have its opponents. The meat industry in
America is a powerful organization that has spent
millions of dollars over decades advertising the benefits of eating meat. Vegetarians point out that lifelong eating habits are difficult to change for many
people, despite research showing that vegetarian diets
can provide the same nutrients as meat-centered
diets.
3900

Resources
BOOKS

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I: Food for Thought. New York: Simon &
Schuster, 2002.
PERIODICALS

American Dietetic Association; Dietitians of Canada.
‘‘Position of the American Dietetic Association and
Dietitians of Canada: Vegetarian Diets.’’ Canadian
Journal of Dietetic Practice and Research 64 (Summer
2003): 62–81.
Fornell-Barratt, Anne, and Adam Drewnowski. ‘‘The Taste
of Health: Nature’s Bitter Gifts.’’ Nutrition Today 37
(July-August 2002): 144-150.
Greydanus, D. E., and D. R. Patel. ‘‘Sports Doping in the
Adolescent Athlete: The Hope, Hype, and Hyperbole.’’
Pediatric Clinics of North America 49 (August 2002):
829-855.
Jenkins, D. J., C. W. Kendall, A. Marchie, et al. ‘‘Type 2
Diabetes and the Vegetarian Diet.’’ American Journal of
Clinical Nutrition 78, Supplement 3 (September 2003):
610S–616S.
Kwok, E., G. Cheng, J. Woo, et al. ‘‘Independent Effect of
Vitamin B12 Deficiency on Hematological Status in
Older Chinese Vegetarian Women.’’ American Journal
of Hematology 70 (July 2002): 186-190.
Lampe, J. W. ‘‘Spicing Up a Vegetarian Diet:
Chemopreventive Effects of Phytochemicals.’’
American Journal of Clinical Nutrition 78, Supplement 3
(September 2003): 579S–583S.
Leitzmann, C. ‘‘Nutrition Ecology: The Contribution of
Vegetarian Diets.’’ American Journal of Clinical Nutrition
78, Supplement 3 (September 2003): 657S– 659S.
Messina, V., V. Melina, and A. R. Mangels. ‘‘A New Food
Guide for North American Vegetarians.’’ Canadian
Journal of Dietetic Practice and Research 64 (Summer
2003): 82–86.
ORGANIZATIONS

American Dietetic Association. 216 West Jackson Blvd.,
Chicago, IL 60606. (312) 899-0040. <http://
www.eatright.org>.
Dietitians of Canada/Les diététistes du Canada. 480
University Avenue, Suite 604, Toronto, ON M5G IV2.
(416) 596-0857. <http://www.dietitians.ca/>.
North American Vegetarian Society (NAVS). PO Box 72,
Dolgeville, NY 13329. (518) 568-7970.
OTHER

Vegetarian Journal. Vegetarian Resource Group (VRG). PO
Box 1463, Baltimore, MD 21203.
Vegetarian Nutrition and Health Letter. 1707 Nichol Hall,
Loma Linda, CA 92350. (888) 558-8703.
Vegetarian Times. 4 High Ridge Park, Stamford, CT 06905.
(877) 321-1796.

Douglas Dupler, MA
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
A coma-like state characterized by open eyes and
the appearance of wakefulness is defined as vegetative.

Cognitive—The ability (or lack of) to think, learn,
and memorize.
Hypermobility—Increased movement of joints.

Description
The vegetative state is a chronic or long-term
condition. This condition differs from a persistent
vegetative state (PVS, a state of coma that lacks both
awareness and wakefulness) since patients have awakened from coma, but still have not regained awareness. In the vegetative state patients can open their
eyelids occasionally and demonstrate sleep-wake
cycles. They also completely lack cognitive function.
The vegetative state is also called coma vigil.

Causes and symptoms
The vegetative state can be caused by:


cardiac arrest



prolonged and profound hypoglycemia (an abnormal
and severe decrease in blood sugar)



carbon monoxide poisoning



head injury



brain hemorrhage



compression of the brainstem



tumors



bilateral hemispheric demyelination (a loss of nerve
cells)



injury of the brain following infections (meningitis or
encephalitis)



neurodegenerative diseases



anencephaly (an abnormality of the brain and skull)



diffuse nerve cell injury

Patients in a vegetative state apparently have
functioning of a special area in the brain called the
reticular activating system (RAS) responsible for
sleep-wake cycles. The connections that integrate
more complex abilities such as awareness are interrupted. Patients in the vegetative state can open and
close eyes spontaneously. They may appear to track or
follow objects with their eyes. Patients may chew and
swallow food placed in the mouth. The vegetative
patient does not respond to sound, hunger, or pain.
Patients cannot obey verbal commands and lack local
motor responses. Additionally these patients cannot
GALE ENCYCLOPEDIA OF MEDICINE

talk in comprehendible terms and they may become
noisy, restless, and hypermobile. These patients are in
a state of arousal but completely lack awareness.

Diagnosis
Diagnosis of vegetative state depends on the primary cause of brain dysfunction. A comprehensive
history and neurological examination, neuroimaging
studies, and chemical analysis of the blood are essential. Additionally, special tests such as cerebrospinal
fluid (CSF, the fluid that bathes and nourishes the
brain and spinal cord) analysis and electroencephalography, (EEG analyzes the electrical activity within
the brain) may be indicated to establish a diagnosis.

Treatment
Treatment is directed to presenting symptoms and
patient needs. Patients require constant monitoring
and assistance with feeding, hydration hygiene,
assisted movement (to help prevent ulcers and blood
clots in the legs), and elimination of waste products.

Alternative treatment
There is no known alternative treatment for vegetative patients.

Prognosis
The prognosis is generally poor and the condition
can persist chronically.

Prevention
There is no known prevention since this state can
occur as a result of unavoidable situations such as
an accident, tumor, and bleeding or genetic
abnormality.
Resources
BOOKS

Goetz, Christopher G., et al, editors. Textbook of Clinical
Neurology. 1st ed. W. B. Saunders Company, 1999.
3901

Vegetative state

KEY TERMS

Vegetative state

Velopharyngeal insufficiency

Goldman, Lee, et al. Cecil Textbook of Medicine. 21st ed. W.
B. Saunders Company, 2000.
Miller, Ronald D., et al, editors. Anesthesia. 5th ed.
Churchill Livingstone, Inc., 2000.

KEY TERMS
Adenoids—Lymph glands just above the tonsils
and the palate.
Cleft palate—Congenital defect marked by a split
in the roof of the mouth.

Laith Farid Gulli, M.D.

Nasopharyngoscopy—A diagnostic procedure that
examines the nasal passageways and pharynx with
an instrument outfitted with an optical system.
Pharynx—A canal located between the mouth cavity and the esophagus.

Velopharyngeal insufficiency
Definition

Tonsillectomy—Surgical removal of the tonsils.
Tonsils—Lymph glands in the throat, just behind
the back teeth.

Velopharyngeal insufficiency is the improper closing of the velopharyngeal sphincter (soft palate muscle) during speech characterized by an acute nasal
quality of the voice.

Description
At the back of the mouth is a circle of structures that
include the tonsils, the tongue, and the palate. During
speech, this apparatus must close off the nose for proper
articulation of the explosive consonants ‘‘p,’’ ‘‘b,’’ ‘‘g,’’
‘‘t,’’ and ‘‘d.’’ If it does not close, there is a snort sound
produced through the nose. Improper function of this
structure also produces a nasal tone to the voice.

Treatment
Velopharyngeal insufficiency is treated with a
combination of surgery and speech therapy. There
are several surgical procedures that can be performed to correct the physical malfunction. They
include:


Pharyngeal flap procedure that moves the skin flap
from the pharynx to the soft palate.



Palatal push-back that separates the hard and soft
palate in order to lengthen the soft palate.



Pharyngoplasty that lengthens the soft palate by
turning the pharyngeal skin flaps.



Augmentation pharyngoplasty that inserts an
implant into the pharyngeal wall to enlarge it, thus
narrowing the velopharyngeal opening.



Velopharyngeal sphincter reconstruction.

Causes and symptoms
There are three main causes for this defect:


Cleft palate is a congenital condition, producing a
defect in the palate that allows air to escape upward
during speech.



If tonsil and adenoid surgery is done improperly,
velopharyngeal insufficiency may result. The occurrence rate is approximately one in every 2,000-3,000
tonsillectomies.



Nerve or muscle disease may paralyze the muscles
that operate the velopharyngeal sphincter.

The primary symptom is the speech impediment.
Some people develop a change in their speaking pattern or a series of facial grimaces to try to overcome
the difficulty. If the condition is acute, regurgitation
through the nose may occur.

Diagnosis
Examination of the velopharyngeal sphincter
through ultrasound scans, fiber-optic nasopharyngoscopy, and videofluoroscopy will reveal the extent of
velopharyngeal insufficiency. Speech and velopharyngeal
sphincter movement are compared to make the diagnosis.
3902

Prognosis
The combination of surgery to correct the insufficiency and speech therapy to retrain the voice successfully alleviate velopharyngeal insufficiency.
Resources
PERIODICALS

Huang M. H., S. T. Lee, and K. Rajendran. ‘‘Anatomic
Basis of Cleft Palate and Velopharyngeal Surgery:
Implications from a Fresh Cadaveric Study.’’ Plastic &
Reconstructive Surgery 101 (Mar. 1998): 613-627.

J. Ricker Polsdorfer, MD
GALE ENCYCLOPEDIA OF MEDICINE

Definition
A vena cava filter is a device inserted into a major
vein to prevent a blood clot from entering the lungs.

Purpose
The purpose of a vena cava filter is to prevent a
blood clot from potentially traveling to the lungs. A
thrombus clot traveling to the lungs is called a pulmonary embolism (PE). A thrombus in the deep venous
system (the part of the circulation that brings blood
back to the heart) represents a disorder of normal
hemostasis (the normal clotting of blood).
Insertion of a vena cava filter is indicated for
patients who:


cannot receive medications that can dissolve the clot
(anticoagulation therapy)



have a thrombus in a deeply situated vein



experiance complication of anticoagulation therapy
such as bleeding



experiance failure of anticoagulation therapy to prevent pulmonary embolism



have an embolus in the lungs (pulmonary embolectomy) removed



have a recurrent embolism while receiving adequate
medications



have significant bleeding complications during
anticoagulation

Precautions
There are no significant precautions concerning
insertion of a vena cava filter. The devices are usually
effective and short-term complications are unusual

Embolus—An embolus (or emboli the plural form)
is a blood clot that has detached from its site of
origin and travels to the lungs (pulmonary artery),
where it can rupture the artery, causing death.
Pulmonary embolism—A traveling thrombus that
has lodged in the pulmonary artery.
Thrombus—A thrombus (or thrombi the plural
form) is a blood clot that can form in a deeply
situated vein.

entering the lungs. There is currently a new type of
filter called the Kim-Ray-Greenfield filter.

Preparation
Insertion of a vena cava filter is an invasive procedure. The patient is prepared for this procedure
using standard surgical protocols. The VCF is commonly implanted in the jugular vein in the neck or the
femoral vein in the groin. The procedure is generally
well tolerated.

Aftercare
This depends on the patient’s health status and
recommendation’s for continued care.

Risks
Many patients have died from PE even with a
vena cava implantation. Use of a VCF is primarily
indicated if there are contraindications for anticoagulation therapy. VCF can increase a patient’s susceptibility for developing recurrent DVT.

Normal results
Description
Vena cava filters are usually inserted in to prevent
PE caused by a thrombosis in a deep vein (DVT).
Approximately 60% of patients who die in a hospital
have evidence of PE during autopsy. The incidence
(number of new cases) of DVT is highest for patients
undergoing surgical repair of a fractured hip.
However, DVT is common in both surgical and medical patients. DVT is found in 29–33% of patients in
medical intensive care units (MICU) and in 27–40% of
patients with a heart attack (myocardial infarction).
Vena cava filters are placed to prevent thrombi from
GALE ENCYCLOPEDIA OF MEDICINE

Patient progresses well and prevention of large
emboli that can cause a PE is successful.

Abnormal results
The desired effect is not accomplished and the
patient develops a PE resulting in death.
Resources
BOOKS

Bone, Roger C. Pulmonary & Critical Care Medicine.
Mosby-Year Book, Inc., 2000.
3903

Vena cava filter

KEY TERMS

Vena cava filter

Venography

Braunwald, Eugene, et al, editors. Heart Disease: A
Textbook of Cardiovascular Medicine. 6th ed. W. B.
Saunders Company, 2001.
Goldman, Lee, et al, editors. Cecil Textbook of Medicine.
21st ed. W. B. Saunders Company, 2000.
Rakel, Robert E., et al, editors. Conn’s Current Therapy.
53rd ed. W. B. Saunders Company, 2001.
Townsend, Courtney M. Sabiston Textbook of Surgery. 16th
ed. W. B. Saunders Company, 2001.
PERIODICALS

Isnard, R., and M. Komajda. ‘‘Thromboembolism in Heart
Failure, Old Ideas and New Challenges.’’ European
Journal of Heart Failure June 2001.
ORGANIZATIONS

American College of Angiology. 295 Northern Blvd., Ste.
104 Great Neck, NY 11021-4701.

Laith Farid Gulli, M.D.

Venereal diseases see Sexually transmitted
diseases

Venography
Definition
Venography is an x-ray test that provides an
image of the leg veins after a contrast dye is injected
into a vein in the patient’s foot.

Purpose
Venography is primarily performed to diagnose
deep vein thrombosis (a condition that can lead to
pulmonary embolism). It is the standard procedure
used to detect this type of disorder. Venography also
can be used to distinguish blood clots from obstructions in the veins, to evaluate congenital vein problems, to see how the deep leg vein valves are
working, and to identify a vein for arterial bypass
grafting.

Precautions
Venography usually is not performed in patients
with kidney (renal) problems.

Description
Venography (also called phlebography, ascending
contrast phlebography, or contrast venography) is an
invasive diagnostic test that provides a constant image
3904

of leg veins on a fluoroscope screen. Venography
identifies the location, extent, and degree of attachment of the blood clots, and enables the condition of
the deep leg veins to be assessed. It is especially useful
when there is a strong suspicion of deep vein thrombosis, but non-invasive tests have failed to identify the
disease.
Venography is the most accurate test for detecting
deep vein thrombosis. It is nearly 100% sensitive and
specific in making this diagnosis (pulmonary embolism
is diagnosed in other ways). Accuracy is crucial since
deep vein thrombosis can lead to pulmonary embolism, a condition that can be fatal.
Venography is not used often, however, because it
is painful, expensive, exposes the patient to a fairly
high dose of radiation, and can cause complications.
In about 5% of cases, there are technical problems in
conducting the test. In addition, the test is less accurate in diagnosing problems below the knee.
Venography takes between 30-45 minutes and can be
done in a physician’s office, outpatient center, or a
hospital.
In 2003, a report said that computed tomography
(CT) scanning could be used to diagnose pulmonary
embolism and deep veinous thrombosis in one examination. By combining CT angiography and CT venography, researchers could look for both conditions in
one procedure with high-speed CT scanners. The procedure was quick and delivered a reduced radiation
dose. However, it has not become accepted as a
replacement for traditional venography and is only
preferred if the patient is clinically stable and requires
immediate diagnosis and treatment.
During the procedure, the patient lies on a tilting
x-ray table. The area where the catheter will be
inserted will be shaved, if necessary, and cleaned.
Sometimes a local anesthetic is injected to numb the
skin at the site of the insertion. A small incision may be
required to make a point for insertion. The catheter is
inserted and the contrast solution (or dye) is slowly
injected. Injection of the dye causes a warm, flushing
feeling in the leg that may spread through the body.
The contrast solution also may cause slight nausea.
About 18% of patients experience discomfort from
the contrast solution.
In order to fill the deep venous system with dye, a
tight band (or tourniquet) may be tied around the
ankle of the foot the dye is injected into, or the lower
extremities may be tilted. The patient is asked to keep
the leg still. The doctor also observes the movement
of the solution through the vein with a fluoroscope. At
the same time, a series of x rays are taken. When the
GALE ENCYCLOPEDIA OF MEDICINE

Contrast solution—A liquid dye injected into the
body that allows veins to be seen by x rays. Without
the dye, the veins could not be seen on x rays.
Deep vein thrombosis—The development or presence of a blood clot in a vein deep within the leg.
Deep vein thrombosis can lead to pulmonary
embolism.
Invasive—A diagnostic test that invades healthy
tissue; in the case of venography, through an incision in a healthy vein.
Pulmonary embolism—An obstruction of a blood
vessel in the lungs, usually due to a blood clot, that
blocks a pulmonary artery. Pulmonary embolism
can be very serious and in some cases is fatal.

bodies. The area around the incision will be sore for
a few days. If there is swelling, redness, pain, or fever,
the doctor should be notified. Pain medication may be
needed. In most cases, the patient can resume normal
activities the next day.

Risks

A venographic image of a patient’s legs with varicose veins.
(Custom Medical Stock Photo. Reproduced by permission.)

Venography also can cause complications such as
phlebitis, tissue damage, and the formation of deep
vein thrombosis in a healthy leg. A rare side effect in
up to 8% of cases is a severe allergic reaction to the
dye. This usually happens within 30 minutes after
injection of the dye and requires medical attention.

test is finished, fluid is injected to clear the dye from
the veins, the catheter is removed, and a bandage is
applied over the site of the injection.

Preparation
Fasting or drinking only clear liquids is necessary
for four hours before the test. However, sometimes the
test is done in an emergency even if the patient has
eaten. The contrast solution contains iodine, to which
some people are allergic. Patients who have allergies or
hay fever, or have had a bad reaction to a contrast
solution, should tell the doctor. A sedative, such as
diazepam (Valium), may be prescribed to help the
patient relax.

Aftercare
Patients should drink large amounts of fluids to
flush the remaining contrast solution from their
GALE ENCYCLOPEDIA OF MEDICINE

Normal results
Normal venography results show proper blood
flow through the leg veins.

Abnormal results
Abnormal venography results show well-defined
filling defects in veins. Findings include:


blood clots



consistent filling defects



an abrupt end of a test dye column



major deep veins that are unfilled



dye flow that is diverted.

These results confirm a diagnosis of deep vein
thrombosis.
3905

Venography

KEY TERMS

Venous access

Resources
PERIODICALS

Abella, H.A. ‘‘CT Dose Techniques Address PE, DVT —
Indirect Venography and Collimation Changes Reduce
Exposure.’’ Diagnostic Imaging November 1, 2003.

Lori De Milto
Teresa G. Odle

Venous access
Definition
Venous access introduces a needle into a vein,
usually for the purpose of withdrawing blood or
administering medication.

Purpose
Venous access is necessary for fluid administration,
medication administration, and obtaining blood for
chemical analysis. Sites for access include veins located
in the peripheral arms or legs, scalp, neck, and bone.
Venous access in children may pose special problems since finding appropriate veins and immobilization may be difficult but essential. For complicated
procedures sedation may be indicated. Venous access
can be performed during emergency situations, for
outpatients, inpatients, and those who require long
term chemotherapy.

Precautions
There are no major precautions for access during
emergency procedures. The main concern during an
emergency would be to secure a portal of entry to
infuse potentially life saving medications and fluids.
For all methods of access the main precautionary
measures include attention to accurate procedures.
Proper procedures are necessary to minimize the possibility of infection, embolism, phlebitis, or destruction
of neighboring tissue.

Description
For peripheral venipuncture the common site is
usually a vein in the arm (the anticubital fossa located
on the opposite side of the elbow) or on the flat bony
area of the hand (dorsum of the hand). Scalp veins are
accessible in infants under one year of age. The selected
vein should be long and straight for needle
3906

accommodation. It should be identified by straightness,
lack of pulsation (characteristic of an artery), and filling
with blood from above (arteries fill from below).
Internal jugular catheterization is performed in the
neck using special bone and muscle landmarks. The
external jugular vein can be cannulized by immobilizing
tilted and rotating the head. The subclavian approach is
a complicated procedure and emergency access can be
performed if attempts for access a vein in other areas
have failed. Intraosseous venous access is usually
accomplished through a leg bone. Catheters implanted
in the front of the chest (anterior chest wall) can accomplish long-term venous access. A large leg vein is preferably used and isolated by dissection. A catheter is
inserted into the vein and they are tied together.

Preparation
For peripheral vein access in the arm, a tourniquet
is applied a few inches over the puncture site. The skin
over the puncture site is sterilized with an alcohol pad.
The needle is inserted and either blood is drawn and
the needle is removed, or a catheter is inserted to place
an intravenous line. Scalp veins can be accessible by
immobilizing the head, shaving the area from hair, and
using a rubber band as a tourniquet. Internal jugular
vein catheterization is accomplished by extending the
patient’s head over the edge of a table or cart and
rotating away from the intended puncture site.
Immobilizing the head and extending it 15–20 degrees
over the edge of a bed or cart and rotating away from
the puncture site can cannulize the external jugular
vein. The subclavian vein access is a complicated procedure and requires sedation and special positioning
(Trendelenburg). A towel should be place in the back
of the area. The skin should be cleansed and the puncture site is anesthetized. For the femoral approach the
leg is externally rotated. The artery should be felt and
along with specific anatomical landmarks the vein can
be localized. The skin should be cleaned and anesthetized. During venous cutdown a large vein near the
anklebone is careful dissected away from underlying
tissues. The area must be properly cleaned and
anesthetize prior to making an incision. A catheter is
inserted and secured in place with sutures.

Aftercare
For simple procedures such as peripheral venous
access, applying simple pressure (to stop bleeding) and
a bandage may be sufficient. For more complicated
procedures, the primary cause for access should be
treated as well as care to avoid or treat potential
complications that may arise from access.
GALE ENCYCLOPEDIA OF MEDICINE

Cannula—Insertion of a tube.
Catheterization—The process of inserting a tubular
instrument into a body cavity to permit passage of
fluid.
Phlebitis— Inflammation of a vein.
Pneumothorax-—The presence of air in the cavity
that surrounds the lungs.

Risks
For access into a peripheral vein, care must be
taken not to puncture both sides of the vein. After
removal of the needle or catheter, a piece of cotton
and pressure should be applied over the puncture site
to prevent unwanted bleeding. Access with a scalp vein
should be preformed with care to avoid hematoma
formation (localized blood clot), accidental puncture
of an artery, or infection. Access into the internal jugular vein in the neck can cause laceration of an artery or
nerve. This procedure can also cause hematoma (blood
clot) formation; damage to local nerves within the area,
pneumothorax, or misplaced catheterization. Venous
access into the external jugular vein can cause hematoma or placement outside the thorax. Subclavian vein
access can cause air to enter a vein (resulting in an air
embolus) or pneumothorax. Cannulation of the
femoral vein in the groin area can cause infection or
thrombophlebitis. Intraosseous venous access commonly performed in a leg bone can cause hematomas,
infection or damage to bone marrow. This procedure
should not be performed if the attempts in one leg is
unsuccessful, the skin over the legs is diseased (from a
burn or infection), or there is a broken leg bone or bone
disease. Venous cutdown can cause infection, loss of the
catheter in the vein, phlebitis, or nerve damage.
Laith Farid Gulli, M.D.
Bilal Nasser, M.Sc.

Venous insufficiency

Syndromes related to venous insufficiency are
caused by valve incompetence. Venous insufficiency is
a chronic (long term) condition. The number of new and
existing cases is dependent on age and gender. Some
patients may have a positive family history. Usually
older persons and females are more commonly affected.
Deep situated and superficial veins can be affected.
Cancer obstructing veins in the pelvis area can cause
superficial venous insufficiency. Deep venous insufficiency is commonly caused by thrombophlebitis, causing
obstruction of valves that regulate blood flow in veins.
Small veins that have been occluded by a thrombosis
may re-canalize (opening up new channels to re-direct
blood flow). These re-canalized veins are inadequate and
cannot correct the impairment of flow. However, larger
veins may still remain occluded. When a thrombosis
occurs the valves that regulate venous blood flow
become thickened and incompetent, rendering them
incapable of regulating back flow of blood. This valvular
incompetence will cause an increase in the presence
within veins (venous hypertension). Venous hypertension
is responsible for most of the symptoms associated with
venous disease. Superficial veins can become dilated
causing varicose veins (veins that bulge and seem tortuous). Leg ulcers can be severe and are responsible for
100,000 cases of disability in the United States alone.

Causes and symptoms
The symptoms of chronic venous insufficiency can
be subjective and objective. Subjective symptoms include
throbbing, cramping, burning sensations, and leg fatigue.
Patients can also develop chronic leg ulcers that may not
heal. Varicose veins in the legs can bleed (since veins are
delicate structures with thin walls) and cause death.
Patients often develop fluid retention (edema) in the
affected limb. Skin changes can occur and affected areas
can become thin, shiny, discolored (blue-purple), and
atrophic. The skin usually becomes thick and tough.

Diagnosis
There are several techniques used to diagnose
venous disease. Electrical impedance plethysmography (IPG) provides a functional evaluation for outflow obstruction ultrasound (a machine that transmits
sound waves) studies can visualize the venous system
in certain areas. Another technique called duplex scanning can measure velocity within a vein.

Definition
Venous insufficiency is described as abnormal
blood flow through veins that can cause local damage,
damage to affected legs, or death.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Periodic elevation of legs and bed rest can help
with leg swelling. Patients are advised to avoid
3907

Venous insufficiency

Description

KEY TERMS

Ventricular aneurysm

section of a blood vessel in the heart that first appears
several days or weeks after an acute myocardial
infarction.

KEY TERMS
Atrophic—A wasting of cells and tissues.
Thrombophlebitis—Venous
formation of a thrombus.

inflammation

with

Thrombus—A clot in the cardiovascular system (the
system that circulates blood throughout the body).

prolonged periods of standing or sitting. Wearing compression stockings can also reduce swelling of the leg.
Mild skin infections can be treated with compresses,
steroids, and, if infection is present, with antibiotics.
Ulcerations can be treated with compresses, possible
surgery, special ointments, and a semi-rigid boot that
helps improve blood flow. Varicose veins can be treated
with elastic stockings. About 15–20% of patients
require surgery, but only after careful evaluation and
specialized testing confirms a beneficial value.

Prognosis
The prognosis is variable and depends on the
progression of disease, extent of damage, and the presence of other diseases, which may affect the cardiovascular system.

A myocardial infarction occurs when a section of
the heart wall is deprived of blood and dies (undergoes
necrosis, or tissue death, and scarring). The heart wall
is mainly muscle. It has two ventricles, the right and
left ventricles, which pump blood to and from the
lungs, and to the body. When part of the heart muscle
dies, pumping power from that part of the wall is lost.
After a myocardial infarction, the part of the heart
wall that did not die must continue pumping blood
and compensate for the dead muscle.
Ventricular aneurysm is one of the complications
that follow a myocardial infarction.
An aneurysm is the outward swelling, or ballooning, of a blood vessel at a weak spot in the wall of the
blood vessel. In the case of ventricular aneurysm, the
aneurysm occurs in the wall of the heart at the spot
where the myocardial infarction occurred. A scar
usually forms in the area of the dead muscle tissue,
and may eventually calcify. Ventricular aneurysms
generally do not rupture. The left ventricle is involved
in most cases of ventricular aneurysm.

Causes and symptoms

Prevention
Persons who have a strong family history, evidence of disease, and/or those who stand on their
legs many hours daily should discuss the option of
elastic stocking with their primary clinician.
Resources
BOOKS

Goroll, Alan H., et al. Primary Care Medicine. 4th ed.
Lippincott, Williams & Wilkins, 2000.
Townsend, Courtney M. Sabiston Textbook of Surgery. 16th
ed. W. B. Saunders Company, 2001.

Laith Farid Gulli, M.D.

Ventricular aneurysm
Definition
Ventricular aneurysm is a complication of a heart
attack (myocardial infarction). It is a ballooning of a
3908

Description

The principle symptom of a ventricular aneurysm
is cardiac insufficiency, a condition in which not
enough blood is being pumped to the body.
Ventricular aneurysm is usually found after a large
infarction in the muscle wall of a ventricle.
Ventricular aneurysm is seldom seen immediately
after a myocardial infarction. It takes several days or
weeks to several months to develop. Frequently, recurrent ventricular irregular heartbeats (arrhythmias) and
low cardiac output result from the presence of a ventricular aneurysm. Blood clots (thrombi) may form on
the inside wall of the aneurysm and produce systemic
blood clots that get stuck in a blood vessel (embolisms), which could lead to stroke or an ischemic leg
(a usually painful condition in which lack of blood
circulation leads to reduced function).

Diagnosis
A number of signs may indicate ventricular aneurysm, including an abnormal precordial impulse in the
heartbeat, persistent elevation of the S-T segment of
an electrocardiogram, and a characteristic bulge seen
GALE ENCYCLOPEDIA OF MEDICINE

Ventricular assist device

Arrhythmia—A disturbance in the beating pattern
of the heart.
Myocardial infarction—Commonly known as a
heart attack, a myocardial infarction occurs when a
part of the heart muscle is deprived of blood and dies.

Definition
A ventricular assist device (VAD) is a mechanical
pump used for temporary blood circulation support. It
decreases the workload of the heart while maintaining
adequate flow and blood pressure.

Purpose
on the heart when x rayed. The bulge is typically seen
when the heart contracts, driving blood to the aorta, in
the systolic phase of the heartbeat. Echolocation
(echocardiography or ultrasound) can confirm the presence of an aneurysm. Cardiac catheterization may be
performed to determine the extent of the aneurysm
and the status of the coronary arteries. Stethoscopic
examination reveals abnormal heart sounds, especially those associated with a backflow of blood from
the left ventricle to the left atrium in systole or contraction beat (mitral regurgitation). This heart murmur is caused by the heart muscles no longer being
able to properly operate the mitral valve.

A VAD is a temporary life-sustaining device.
VADs can replace the left ventricle (LVAD), the
right ventricle (RVAD), or both ventricles (BIVAD).
They are used when the heart muscle is damaged and
needs to rest in order to heal or when blood flow from
the heart is inadequate. VADs can also be used as a
bridge in patients awaiting heart transplantation or in
patients who have rejected a transplanted heart.
Examples of patients who might be candidates for
a VAD are those who:


have suffered a massive heart attack



cannot be weaned from heart-lung bypass after treatment with intravenous fluids, medications, and insertion of a balloon pump in the aorta



have an infection in the heart wall that does not
respond to conventional treatment



are awaiting a heart transplant and are unresponsive
to drug therapy and intravenous fluids



are undergoing high-risk procedures to clear the
blockages in a coronary artery

Treatment
Most cases of ventricular aneurysm are treated by
close medical follow-up and limiting patient activity.
Surgical removal of the aneurysm is an option when
persistent left ventricular failure or arrhythmia occurs,
and the aneurysm is large. Vasodilators, diuretics, and
digoxin are used to treat heart failure. Anticoagulant
drugs are used to prevent the formation of blood clots.
Antiarrhythmic drugs are used to treat heart
arrhythmias.

Prognosis
Ventricular aneurysm occurs more frequently
than is commonly thought. Based on postmortem
examination, ventricular aneurysm occurs in as many
as 15% of myocardial infarction cases. Patients with a
large ventricular aneurysm in the left ventricle have a
reduced survival rate. Many patients have mild symptoms which are not life-threatening. The survival rate
is dependent on the function of the left ventricle.

Although one in five people suffer left side ventricular failure, only a minority are candidates for VADs.
To be considered for a VAD, patients must meet specific criteria concerning blood flow, blood pressure,
and general health.

Precautions
Poor candidates for a VAD include those with:


irreversible renal failure



severe disease of the vascular system of the brain



cancer that has spread (metastasized)

Resources



severe liver disease

BOOKS



blood clotting disorders

Alexander, R. W., R. C. Schlant, and V. Fuster, editors. The
Heart. 9th ed. New York: McGraw-Hill, 1998.



severe lung disease



infections that do not respond to antibiotics



extreme youth or age

John T. Lohr, PhD
GALE ENCYCLOPEDIA OF MEDICINE

3909

Ventricular assist device

KEY TERMS

Ventricular ectopic beats

KEY TERMS
Coronary blood vessels—The arteries and veins
that supply blood to the heart muscle.
Diaphragm—The muscle that separates the chest
cavity from the abdominal cavity.
Ventricle—The heart has four chambers. The right
and left ventricles are at the bottom of the heart and
act as the body’s main pumps.

Description
There are four types of VADs, each appropriate
for a different condition. Surgery to install a VAD is
performed under general anesthesia in a hospital operating room. An incision is made in the chest, then
catheters are inserted into the heart and the correct
artery. The surgeon sutures the catheters in place, then
attaches tubing to connect the catheters to the pump.
The pump stays outside the body. Once it is turned on,
blood flows out of the diseased ventricle and into the
pump, then is returned to the correct blood vessel
leaving the heart.

paralysis of the diaphragm, respiratory failure, kidney
failure, failure of the VAD, damage to the coronary
blood vessels, stroke, and infection.
Sometimes when the left ventricle is supported,
the right ventricle begins to need assistance. If VADs
are inserted in both ventricles, the heart may become
so dependent on their support that they cannot be
removed.

Normal results
Because conditions for which VADs are used vary
widely and because of the high risks associated with
VAD insertion, the outcome of surgery cannot be
predicted.
Resources
BOOKS

Zaret, Barry L., et al., editors. ‘‘Ventricular Assist Device.’’
In The Patient’s Guide to Medical Tests. Boston:
Houghton Mifflin,1997.
OTHER

‘‘Ventricular Assist Devices.’’ Department of Biological and
Agricultural Engineering. New York State University.
<http://www.bae.ncsu.edu>.

Tish Davidson, A.M.

Preparation
Before the operation the patient meets with an
anesthesiologist to determine any special conditions
that will affect the administration of anesthesia.
Standard preoperative blood and urine studies are
performed, and the heart is monitored both before
and during the operation with an electrocardiograph.

Aftercare
The patient is monitored in intensive care, with
follow-up blood, urine, and neurological studies.
Blood thinning medications are given to prevent
blood clotting.
Except for those patients awaiting a heart transplant, patients are slowly and gradually weaned from
the VAD. Even when patients no longer need the
VAD, they will require supportive drug therapy and/
or a balloon pump inserted in the aorta.

Risks
VAD insertion carries risks of severe complications. Bleeding from surgery is common and occurs
in as many as 30-50% of patients. Other complications
include the development of blood clots, partial
3910

Ventricular ectopic beats
Definition
A ventricular ectopic beat (VEB) is an extra heartbeat originating in the lower chamber of the heart.
This beat, also called a premature ventricular contraction (PVC), occurs before the beat triggered by the
heart’s normal function.

Description
Ventricular ectopic beats are common and do not
indicate a problem in people without heart disease.
However, if a person has aortic stenosis, heart failure,
or a previous heart attack, VEBs may be followed by
ventricular tachycardia and fibrillation, which can lead
to sudden death.

Causes and symptoms
Although the origin of a VEB is well documented,
the exact cause or causes are not well understood.
GALE ENCYCLOPEDIA OF MEDICINE

Angioplasty—A surgical procedure which dilates a
narrowed or blocked part of an artery.
Aortic stenosis—A stiffening of the artery which
carries blood from the heart to the body.
Beta-blockers—A class of medication used to
block the cellular response to chemicals normally
present in the body.
Coronary artery—The vessel which brings blood to
the muscle of the heart.
Fibrillation—Rapid, uncoordinated quivering of
the heart.
Heart failure—A term used when the heart is
unable to pump enough blood to supply the needs
of the body.

Some physicians believe the beat is caused by a trigger
of specific origin, while other physicians believe the
beat is random. Occasional ventricular ectopic beats
occur in healthy people. If there is no evidence of heart
disease, there is little or no danger to the individual.
A single ventricular ectopic beat has very little
effect on the pumping ability of the heart and usually
does not cause any symptoms. If a symptom is felt, it is
the feeling of a strong or skipped beat, often described
as a thump, kick, or flip-flop. Sometimes, the sensation is referred to as a fullness in the neck.

with beta-blockers will be recommended. In addition,
angioplasty or coronary artery bypass surgery may
relieve any underlying coronary artery blockage and
reduce the danger of sudden death.
Treatment with antiarrhythmic drugs can suppress
VEBs, but they can also increase the risk of a fatal
abnormal rhythm. Often, extensive electrophysiologic
testing and risk evaluation will be done before this
method of treatment is prescribed.

Prognosis
In healthy people, VEBs are inconsequential. If
the person with heart disease is able to find an effective
means of controlling ventricular ectopic beats, the
outlook is good.

Prevention
Occasional ventricular ectopic beats in healthy
people do not need to be prevented. People with a
history of heart disease can usually control VEBs
with medication.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dorothy Elinor Stonely

Ventricular failure see Heart failure
Diagnosis
Ventricular ectopic beats are easily seen on an
electrocardiogram.

Treatment
If a person is otherwise healthy, the only treatment needed is to decrease stress and limit the use of
alcohol and caffeine. Cold medicines, available without prescription, sometimes contain drugs (e.g., decongestants) that stimulate the heart and should be used
with caution.
If symptoms are uncomfortable, or the pattern of
VEBs indicates a problem, the physician may prescribe drug therapy. Beta-blockers are quite safe and
are usually tried first.
A person who has a history of heart attack or
heart disease, and is experiencing frequent or complex
VEBs, is at greater risk of sudden death. Drug therapy
GALE ENCYCLOPEDIA OF MEDICINE

Ventricular fibrillation
Definition
Ventricular fibrillation is a very rapid, uncoordinated, ineffective series of contractions throughout the
lower chambers of the heart. Unless stopped, these
chaotic impulses are fatal.

Description
When the ventricles begin to quiver and do not
employ coordinated contractions, the heart is said to
be fibrillating. In this condition the ventricles cannot
pump blood from the heart. Ventricular fibrillation
(V-fib) is the worst kind of abnormal heart rhythm,
and is a form of cardiac arrest. It involves the pumping
3911

Ventricular fibrillation

KEY TERMS

Ventricular fibrillation

of the lower chambers of the heart, while atrial fibrillation involves the upper chambers.

Causes and symptoms
Ventricular fibrillation often is associated with
acute ischemic events (ischemia involves the deprivation of oxygenated blood to an area of tissue), and
with chronic ischemic heart disease. It is frequently
seen immediately following a heart attack. It also
may develop during hypoxia, atrial fibrillation, or
improper grounding of electrical devices. An extremely low level of potassium in the blood also can
cause ventricular fibrillation.
The first, and usually the only, symptom of V-fib
is sudden unconsciousness.

Diagnosis
When an individual suddenly collapses, the possibility of ventricular fibrillation should be considered
immediately. A quick assessment usually shows no
pulse or heartbeat. The diagnosis of ventricular fibrillation is confirmed with an electrocardiogram.

Treatment
Basic life support with standard cardiopulmonary
resuscitation (CPR) must be started within a few minutes, followed as soon as possible with cardioversion.
Cardioversion is an electric shock delivered to the
heart to stop the fibrillating. Early defibrillation is the
key to survival. If left untreated, irreversible brain
damage, due to lack of oxygen to the brain, occurs
after about five minutes. After the heart resumes its
normal rhythm, medications are given to help maintain the rhythm.
Research continues into methods to deliver defibrillation as soon as possible to those experiencing
ventricular fibrillation. One of the studies addressed
in 2003 researched various clinical trials that
implanted defibrillators into patients to prevent sudden cardiac death. The devices worked in many
instances but more proof of their success was needed
for widespread use.

Prognosis
Early and effective CPR may provide the time
necessary for medical personnel to arrive with a defibrillator. If a defibrillator is able to promptly restore a
normal rhythm, up to 25% of victims are able to leave
the hospital without evidence of brain damage.
3912

KEY TERMS
Atrial fibrillation—A condition in which the upper
chambers of the heart quiver instead of contracting
effectively
Cardiopulmonary resuscitation (CPR)—Using rescue breathing and chest compressions to help a
person whose breathing and heartbeat have
stopped
Cardioversion—An electrical shock delivered to
the heart to restore a normal rhythm
Electrocardiogram—A visual representation of the
heart beat
Heart failure—A term used when the heart is
unable to pump enough blood to supply the needs
of the body
Hypoxia—Insufficient oxygen in the cells of the
body
Ischemic—Insufficient blood reaching the tissues

If ventricular fibrillation occurs in the hospital in
conjunction with a heart attack, defibrillation has a
95% success rate. If shock and heart failure are present
at the time, even with immediate defibrillation, only
about 30% of those stricken are successfully restored
to a normal heart rate.

Prevention
A healthy lifestyle to reduce the risk of heart diseases which lead to ventricular fibrillation is the best
prevention. For people who have experienced an episode of V-fib, an internal cardioverter-defibrillator
may prevent further episodes.
Resources
PERIODICALS

Ezekowitz, Justin A., et al. ‘‘Implantable Cardioverter
Defibrillators in Primary and Secondary Prevention: A
Systematic Review of Randomized, Controlled Trials.’’
Annals of Internal Medicine January 2002: 445.
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dorothy Elinor Stonely
Teresa G. Odle
GALE ENCYCLOPEDIA OF MEDICINE

Definition
A ventricular septal defect is a hole in the wall of
the heart (septum) that separates the left lower chamber (left ventricle) from the right lower chamber (right
ventricle). The hole allows blood to flow from the left
ventricle to the right ventricle instead of entering the
aorta for distribution throughout the body.
Ventricular septal defect is one of a group of heart
problems found in newborn babies that are collectively called congenital heart disease.

Echocardiogram—An image of the heart produced
by an instrument that uses sound waves to create
image the heart.
Electrocardiogram—A graph of the heart’s beating
action.
Endocarditis—An inflammation of the interior lining of the heart that is frequently caused by infectious agents.

Description
The heart has four chambers. The two lower chambers are called ventricles and are responsible for pumping blood. The right ventricle pumps blood to the lungs
and the left ventricle pumps blood throughout the
body. If there is a hole in the septum that separates
the two ventricles, blood from the left ventricle can
enter the right ventricle. This blood recycles through
the lungs before returning to the left ventricle. This
results in less oxygenated blood reaching the body. If
the hole is sufficiently large, the lack of oxygen being
delivered to the body can cause severe problems, including heart failure and breathlessness. Approximately
0.7% of all babies have a congenital heart defect. Of
these, 20% have a ventricular septal defect.

Causes and symptoms
Congenital heart defects are errors in the development of the heart structure. They occur early in the life of
the embryo. There is no known cause of congenital heart
defects. They can be associated with several diseases,
such as German measles (rubella) and Down syndrome.
Genetics does not seem to play a role in ventricular septal
defect. People with a heart defect do not have an
increased chance of passing it on to their children.
Symptoms result from a reduced amount of oxygen going to the body. Symptoms are proportional to
the size of the defect. They may appear at any time in
the life of the child. In cases where the hole in the
septum is very small, few or no symptoms may appear
and the child may develop normally. In cases where
the ventricular septal defect is large, the newborn will
shows signs of heavy breathing, sweating, and feeding
difficulties. Children with this defect tire easily.
Ventricular septal defect can also result in stunted
growth resulting from insufficient oxygen being delivered to the growing body. Children with ventricular
GALE ENCYCLOPEDIA OF MEDICINE

An angiogram of a ventricular septal defect. This is a hole in
the ventricular septum causing blood to flow from the left
ventricle (right of image) to the right ventricle and to the
lungs. The bent catheter at the center, which is used to take
the angiogram, passes through the hole between the ventricles. (Photograph by Simon Fraser, Photo Researchers, Inc.
Reproduced by permission.)

septal defect tend to suffer more frequent colds and
pneumonia, and have a higher rate of inflammation
and infection of the heart (endocarditis).

Diagnosis
The condition is first suspected based on observation of the child. The physician will listen to the heart
with a stethoscope (auscultation) to detect a heart
murmur. X rays, electrocardiogram (ECG), and echocardiography can all be used to evaluate ventricular
septal defect.
3913

Ventricular septal defect

KEY TERMS

Ventricular septal defect

Ventricular shunt

Treatment
Most small holes close without treatment. Often,
as the child grows, the hole closes or becomes smaller.
If the hole is large or fails to close, the child is usually
treated with drugs. Holes that persist and are causing
problems in development are corrected by open heart
surgery. Usually, surgery is performed after one year
of age, but before the child enters school. This allows
time for a trial of drug therapy, which could potentially eliminate the need for surgery. The operation is
generally safe.

Prognosis
Children with small septal defects tend to develop
normally and without any effect on their ability to
participate in physical activities. Surgery allows children with larger defects to live nearly normal lives.
Resources
BOOKS

Alexander, R. W., R. C. Schlant, and V. Fuster, editors.
TheHeart. 9th ed. New York: McGraw-Hill, 1998.

John T. Lohr, PhD

Ventricular shunt
Definition
Ventricular shunt is a surgical procedure in which
a tube is placed in one of the fluid-filled chambers
inside the brain (ventricles). The fluid around the
brain and the spinal column is called the cerebrospinal
fluid. When infection or disease causes an excess of
this cerebrospinal fluid in the ventricles, the shunt is
placed to drain it and thereby relieve excess pressure.

Purpose
Ventricular shunt relieves hydrocephalus, a condition in which the ventricles are enlarged. In hydrocephalus, pressure from the cerebrospinal fluid usually
increases. It may be caused by tumor of the brain or of
the membranes covering the brain (meninges), infection of or bleeding into the cerebrospinal fluid, or
inborn malformations of the brain. Symptoms of
hydrocephalus may include headache, personality disturbances and loss of intellectual abilities (dementia),
3914

problems in walking, irritability, vomiting, abnormal
eye movements, or a low level of consciousness.
Normal pressure hydrocephalus is associated with
progressive dementia, problems in walking, and loss of
bladder control (urinary incontinence). Even though
the cerebrospinal fluid is not thought to be under
increased pressure in this condition, it may also be
treated by ventricular shunting.

Precautions
As with any surgical procedure, the surgeon must
know about any medications or health problems that
may increase the patient’s risk. Because infections are
both common and serious complications, antibiotics
are often given before and after surgery.

Description
The ventricular shunt tube is placed to drain fluid
from the ventricular system in the brain to the cavity of
the abdomen or to the large vein in the neck (jugular
vein). Therefore, surgical procedures must be done
both in the brain and at the drainage site. The tubing
contains valves to insure that fluid can only flow out of
the brain and not back into it. The valve can be set at a
desired pressure to allow cerebrospinal fluid to escape
whenever the pressure level is exceeded.
A small reservoir may be attached to the tubing
and placed under the scalp. This reservoir allows samples of cerebrospinal fluid to be removed with a syringe to check the pressure. Fluid from the reservoir can
also be examined for bacteria, cancer cells, blood, or
protein, depending on the cause of hydrocephalus.
The reservoir may also be used to inject antibiotics
for cerebrospinal fluid infection or chemotherapy medication for meningeal tumors.

Preparation
The diagnosis of hydrocephalus should be confirmed by diagnostic techniques that make images of
the brain, such as computed tomography scan (CT
scan) or magnetic resonance imaging (MRI), before
the shunting procedure is performed. These techniques
will also show any associated brain abnormalities.
Cerebrospinal fluid should be examined if infection or
tumor of the meninges is suspected. Patients with
dementia or mental retardation should undergo neuropsychological testing to establish a baseline psychological profile before the shunting procedure.
Patients with normal pressure hydrocephalus may
experience a temporary improvement in walking and
GALE ENCYCLOPEDIA OF MEDICINE

Cerebrospinal fluid—Fluid bathing the brain and
spinal cord.
Computed tomography (CT) scan—An imaging
technique in which cross-sectional x rays of the
body are compiled to create a three-dimensional
image of the body’s internal structures.
Dementia—Progressive loss of mental abilities.
Magnetic resonance imaging (MRI)—An imaging
technique that uses a large circular magnet and
radio waves to generate signals from atoms in the
body. These signals are used to construct images of
internal structures.

mental abilities upon removal of a moderate amount
of cerebrospinal fluid. This improvement may be an
indication that shunting will improve their condition.
However, patients who do not improve after temporary cerebrospinal fluid drainage may still benefit from
ventricular shunt. When a case is in doubt, continuous
monitoring of cerebrospinal fluid pressure (which in
itself requires a surgical procedure) may indicate
whether shunting is likely to be helpful.

may be injured. If cerebrospinal fluid pressure is lowered too much, patients may have severe headaches,
often with nausea and vomiting, whenever they sit up or
stand.

Normal results
Of patients with normal pressure hydrocephalus
who are treated with shunting, 25-80% experience
long-term improvement. Normal pressure hydrocephalus is more likely to improve when it is caused by
infection of or bleeding into the cerebrospinal fluid
than when it occurs without an underlying cause.
Walking difficulties and bladder control are more
likely to improve than dementia is.
After shunting, the ventricles get smaller within
three or four days. This shrinkage occurs even when
hydrocephalus has been present for a year or more.
Clinically detectable signs of improvement occur
within a few weeks. The cause of hydrocephalus, duration of hydrocephalus before shunting, and associated
brain abnormalities affect the outcome.
Resources
ORGANIZATIONS

American Academy of Neurology. 1080 Montreal Ave., St.
Paul, MN 55116. (612) 695-1940. <http://
www.aan.com>.

Aftercare
To avoid infections at the shunt site, the area
should be kept clean. Cerebrospinal fluid should be
checked periodically by the doctor to be sure there is
no infection or bleeding into the shunt. Cerebrospinal
fluid pressure should be checked to be sure the shunt is
operating properly. The eyes should be examined regularly because shunt failure may damage the nerve to
the eyes (optic nerve). If not treated promptly, damage
to the optic nerve causes irreversible loss of vision.
Patients or caregivers should understand the lifethreatening nature of shunt problems. All symptoms
and signs of potential shunt failure or infection must
be taken seriously.

Laurie Barclay, MD

Ventricular tachycardia
Definition
Ventricular tachycardia (V-tach) is a rapid heart
beat that originates in one of the lower chambers (the
ventricles) of the heart. To be classified as tachycardia,
the heart rate is usually at least 100 beats per minute.

Description
Risks
Complications of shunting occur in 30% of cases,
but only 5% are serious. Serious and long-term complications are bleeding under the outermost covering
of the brain (subdural hematoma), infection, stroke,
and shunt failure. Infection at the shunt site may
cause a loss of intelligence. When shunts drain to the
abdomen (ventriculoperitoneal shunts), fluid may
accumulate in the abdomen or abdominal organs
GALE ENCYCLOPEDIA OF MEDICINE

A rapid heart rate can originate in either the left or
right ventricle. Ventricular tachycardia which lasts
more than 30 seconds is referred to as sustained ventricular tachycardia. A period of three to five rapid
beats is called a salvo, and six beats or more lasting less
than 30 seconds is called nonsustained ventricular
tachycardia. Rapid ventricular rhythms are more serious than rapid atrial rhythms because they make the
heart extremely inefficient. They also tend to cause
3915

Ventricular tachycardia

KEY TERMS

Ventricular tachycardia

KEY TERMS
Atrial—Having to do with the upper chambers of
the heart.
Cardiomyopathy—A disease of the heart muscle.
Cardioversion—A electrical shock delivered to the
heart to restore a normal rhythm.
Coronary artery—The artery that supplies blood to
the heart muscle itself.

An electrocardiographic image indicating a rapid heart beat.
(Custom Medical Stock Photo. Reproduced by permission.)

Electrocardiogram—A visual representation of the
heart beat.
Fibrillation—Rapid, uncoordinated, quivering of
the heart.

more severe symptoms, and have a much greater tendency to result in death.

Palpitations—Uncomfortable feeling of the heart
beat in the chest.
Valvular—Having to do with the valves inside the
heart.

Although generally considered to be among the
life-threatening abnormal rhythms, harmless forms of
sustained V-tach do exist. These occur in people without any structural heart disease.

Causes and symptoms
Most ventricular tachycardias are associated with
serious heart disease such as coronary artery blockage,
cardiomyopathy, or valvular heart disease. V-tach is
often triggered by an extra beat originating in either
the right or left ventricle. It also occurs frequently in
connection with a heart attack. V-tach commonly
occurs within 24 hours of the start of the attack. It
must be treated quickly to prevent fibrillation. After
48 to 72 hours of the heart attack, the risk of ventricular tachycardia is small. However, people who have
suffered severe damage to the larger anterior wall of
the heart have a second danger period, because V-tach
often occurs during convalescence from this type of
heart attack.
Sustained ventricular tachycardia prevents the
ventricles from filling adequately so the heart can not
pump normally. This results in loss of blood pressure,
and can lead to a loss of consciousness and to heart
failure.
The individual with V-tach almost always experiences palpitation, though some episodes cause no
symptoms at all.

Diagnosis
Diagnosis is easily made with an electrocardiogram.
3916

Treatment
Any episode of ventricular tachycardia that
causes symptoms needs to be treated. An episode
that lasts more than 30 seconds, even without symptoms, also needs to be treated. Drug therapy can be
given intravenously to suppress episodes of V-tach. If
blood pressure falls below normal, a person will need
electric cardioversion (‘‘shock’’) immediately.

Prognosis
With appropriate drug or surgical treatment, ventricular tachycardia can be controlled in most people.

Prevention
A person susceptible to sustained ventricular
tachycardia often has a small abnormal area in the
ventricles that is the source of the trigger event. This
area can sometimes be surgically removed. If surgery is
not an option, and drug therapy is not effective, a
device called an automatic cardioverter-defibrillator
may be implanted.
Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300. <http://
www.americanheart.org>.

Dorothy Elinor Stonely
GALE ENCYCLOPEDIA OF MEDICINE

Vertigo see Dizziness
Vesicle see Skin lesions

Vesicoureteral reflux

VUR alone does not usually cause symptoms.
Symptoms develop when an infection has set in. The
usual symptoms of infection include frequent need to
urinate, pain or burning with urination, and blood or
pus in the urine. Occasionally, VUR is suspected when
a child has a difficult time becoming toilet trained. In
these cases, the bladder may become irritable and
spasm, because it is never totally empty of urine.
When the kidneys have been damaged, high blood
pressure may develop.

Definition
Vesicoureteral reflux (VUR) refers to a condition
in which urine flows from the bladder, back up the
ureter, and back into the kidneys.

Description
The normal flow of urine begins in the collecting
system of each kidney. Urine then flows out of each
kidney and into a tube called the ureter. Each ureter
leads into the bladder, where the urine collects until it
is passed out of the body. Normally, urine should flow
only in this direction. In vesicoureteral reflux, however, urine that has already collected in the bladder is
able to flow backwards from the bladder, up the
ureter, and back into the collecting system of the kidney. VUR may be present in either one or both ureters.

Diagnosis
VUR is diagnosed by taking a series of x-ray
pictures. These are taken after putting a small tube
(catheter) into the bladder. The bladder is then filled
with a dye solution which lights up on the x-ray picture. Pictures are taken immediately, followed by
x rays taken while the patient is urinating. This will
allow reflux to be demonstrated, and will reveal
whether the level of reflux increases when pressure
increases during urination. Reflux is then graded
based on the height and effects of the VUR:


Grade I. VUR enters just the portion of the ureter
closest to the bladder. The ureter appears normal in
size.



Grade II. VUR enters the entire ureter, and goes up
into the collecting system of the kidney. The ureter
and the collecting system appear normal in size and
structure.



Grade III. VUR enters the entire ureter and kidney
collecting system. Either the ureter or the collecting
system are abnormal in size or shape.



Grade IV. Similar to Grade III, but the ureter is
greatly enlarged.



Grade V. Similar to Grade IV, but the ureter is also
abnormally twisted/curved, and the collecting system is greatly enlarged, with absence of the usual
structural details.

Vesicoureteral reflux causes damage to the kidneys in two ways:




The kidney is not designed to withstand very much
pressure. When VUR is present, back pressure of the
urine on the kidney is significant. This can damage
the kidney.
The kidney is usually sterile, meaning that no bacteria are normally present within it. In VUR, bacteria
that enter through the urinary tract may be carried
back up the ureter with the urine. These bacteria can
enter the kidney, causing severe infection.

Causes and symptoms
Most cases of VUR are due to a defect in the way
the ureter is implanted into the bladder. The angle may
be wrong, or the valve (which should allow urine only
one-way entrance into the bladder) may be weak.
Structural defects of the urinary system may also
cause VUR. These include a situation in which two
ureters leave a kidney, instead of the usual one (duplicated ureters), and in which the ureter is greatly
enlarged at the end leading into the bladder
(ureterocele).
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
Treatment depends on the grade that is diagnosed.
In grades I and II, the usual treatment involves longterm use of a small daily dose of antibiotics to prevent
the development of infections. The urine is tested regularly to make sure that no infection occurs. The
kidneys are evaluated regularly to make sure that
they are growing normally and that no new scarring
has occurred. Grade III VUR can be treated with
antibiotics and careful monitoring. New infections,
scarring, or stunting of kidney growth may result in a
3917

Vesicoureteral reflux

Verrucae see Warts

Vibriosis

Vestibulitis see Labyrinthitis

KEY TERMS
Bladder—The muscular sac which receives urine
from the kidneys, stores it, and ultimately works to
remove it from the body during urination.
Reflux—A condition in which flow is backwards
from normal.

Viagra see Sildenafil citrate
Vibrio cholera infection see Cholera
Vibrio parahemolyticus infection see
Vibriosis

Ureter—A muscular tube leading from the kidney
to the bladder, down which the urine flows.

Vibriosis
need for surgery. Grades IV and V are extremely likely
to require surgery.
Surgery for VUR consists of reimplanting the
ureters into the bladder at a more normal angle. This
usually improves the functioning of the valve leading
into the bladder. When structural defects of the urinary system are present, surgery will almost always be
required to repair these defects.

Prognosis

Definition
Vibriosis is a disease caused by an infection with
bacteria of the Vibrio genus, most commonly Vibrio
parahemolyticus or Vibrio vulnificus. Vibrio bacteria
cause diarrhea, skin infections, and/or blood infections. The diarrhea-causing Vibrio parahemolyticus is
a relatively harmless infection, but Vibrio vulnificus
infection, though rare, can lead to blood poisoning
and death in many cases.

Description

Prognosis is dependent on the grade of VUR.
About 80% of children with grades I and II VUR
simply grow out of the problem. As they grow, the
ureter lengthens, changing its angle of entry into the
bladder. About 50% of children with grade III VUR
will require surgery. Nearly all children with grades IV
and V VUR will require surgery. In these cases, it is
usually best to perform surgery at a relatively young
age, in order to avoid damage and scarring to the
kidneys.

Prevention
While there is no known method of preventing
VUR, it is important to note that a high number of
the siblings of children with VUR will also have VUR.
Many of these siblings (about 36%) will have no
symptoms, but will be discovered through routine
examinations prompted by their brother’s or sister’s
problems. It is important to identify these children, so
that antibiotic treatment can be used to prevent the
development of infection and kidney damage.
Resources

Vibriosis is a general term referring to an infection by
any member of the large group of Vibrio bacteria. The
bacteria that causes cholera is in this group. Alternate
names include non-cholera Vibrio infection, Vibrio parahemolyticus infection, and Vibrio vulnificus infection.
Vibrio parahemolyticus and Vibrio vulnificus are
found in salt water. Infection with either of these two
bacteria primarily occurs through eating contaminated raw seafood. Raw oysters are the usual source,
although other seafood can carry the bacteria.
Vibrio parahemolyticus causes severe diarrhea.
Vibrio vulnificus may cause diarrhea, but in persons
with an underlying disease it may cause severe blood
infections (septicemia or blood poisoning). Contact of
a wound with seawater or contaminated seafood can
lead to a Vibrio vulnificus skin infection.
Vibriosis is not very common in the United States.
Most cases occur in coastal states between June and
October. Between 1988 and 1991, there were only 21
reported cases of Vibrio parahemolyticus infection in
the United States. Between 1988 and 1995, there were
over 300 reports of Vibrio vulnificus infection in the
United States.

ORGANIZATIONS

American Foundation for Urologic Disease. 300 West Pratt
St., Suite 401, Baltimore, MD 21201. (800) 242-2383.

Rosalyn Carson-DeWitt, MD
3918

Causes and symptoms
Vibriosis is caused by eating seafood contaminated with Vibrio parahemolyticus or Vibrio vulnificus.
GALE ENCYCLOPEDIA OF MEDICINE

Persons at risk for severe, often fatal vibriosis
include those with liver disease (cirrhosis), excess iron
(hemochromatosis), thalassemia (a blood disorder),
AIDS, diabetes, or those who are immunosuppressed.
Symptoms of intestinal infection occur within two
days of eating contaminated seafood. Symptoms last
for two to 10 days and include watery diarrhea,
abdominal cramps, nausea, vomiting, headache, and
possibly fever. Symptoms of a blood infection develop
one to two days after eating contaminated seafood,
and include fever, chills, low blood pressure, and large
fluid-filled blisters on the arms or legs. Similar blisters
can also be produced by a Vibrio vulnificus skin
infection.

Diagnosis
Vibriosis can be diagnosed and treated by an
infectious disease specialist. It is diagnosed when
Vibrio bacteria are grown from samples of stool,
blood, or blister fluid. The symptoms and a recent
history of eating raw seafood are very important
clues for diagnosis.

Treatment
To counteract the fluid loss resulting from diarrhea, the patient will receive fluids either by mouth or
intravenously. Antibiotics are not helpful in treating
Vibrio parahemolyticus diarrhea.
However, Vibrio vulnificus infections are treated
with antibiotics such as tetracycline (Sumycin,
Achromycin V), or doxycycline (Monodox) plus ceftazidime (Ceftaz, Fortraz, Tazicef). One out of five
patients with vibriosis requires hospitalization.

Prognosis
Most healthy persons completely recover from
diarrhea caused by Vibrio bacteria. Vibrio vulnificus
blood infection affects persons with underlying illness
and is fatal in half of those cases. Vibrio vulnificus
wound infections are fatal in one quarter of the cases.

Prevention
Contamination with Vibrio bacteria does not
change the look, smell, or taste of the seafood.
Vibriosis can be prevented by avoiding raw or
GALE ENCYCLOPEDIA OF MEDICINE

undercooked shellfish, keeping raw shellfish and its
juices away from cooked foods, and avoiding contact
of wounded skin with seawater or raw seafood.
Resources
OTHER

Center for Food Safety and Applied Nutrition. <http://
vm.cfsan.fda.gov>.

Belinda Rowland, PhD

Viral diarrhea see Rotavirus infections
Viral meningitis see Meningitis
Visceral l see Roundworm infections

Vision training
Definition
Vision training, also known as vision therapy or
orthoptics, consists of a variety of programs to
enhance visual performance. It includes treatments
for focusing, binocularity, and eye movement problems. Vision training is generally provided by an
optometrist (O.D.).

Purpose
While visual acuity refers to how clearly each eye
can see, vision training addresses how well the two
eyes work together as a team. When looking at an
object, the eyes must focus on the object (e.g., focusing
for near or far objects). This involves the lens system of
the eyes. The eyes must also work as a team and point
at the same object so that the person does not see
double. Aiming precisely at the same object will aid
in depth perception (stereopsis) and seeing objects in
three-dimensions (3D).
Although crossed eyes (strabismus) is an obvious
condition, many defects in the coordination of eye
movement are far less apparent. Even so, they can
cause problems in reading, driving vehicles, and
other complex tasks that require the integrated function of eyes and body. It is the goal of vision therapy to
improve these subtle interactions using carefully
devised exercises and devices.
The discipline, called ‘‘behavioral optometry,’’
involves a careful evaluation of visual function, concentrating on complex skills such as rapid reading,
distance perception, peripheral field awareness,
3919

Vision training

These bacteria damage the inner wall of the intestine,
which causes diarrhea and related symptoms. Vibrio
vulnificus can get through the intestinal wall and into
the bloodstream.

Vision training

accommodative facility, and the coordinated movement of each eye in relationship to the other. From
that assessment the doctor goes on to design a course
of exercises to correct the problems discovered. Like
any other type of training, success requires practice
and persistence until habits and reflexes can be
retrained.
There are a number of different techniques and
instruments used in vision therapy; the field is evolving
rapidly in many directions. Some computerized exercises are being developed that promise better patient
motivation. A device called the Dynavision apparatus,
has produced positive results in retraining stroke victims to operate motor vehicles. And traditional forms
of vision therapy have increased reading efficiency in
an older age group (62 to 75 years).
Because the goal of vision training is to improve
visual efficiency and visual processing, people having
problems reading should consider a vision training evaluation. Children rubbing their eyes while reading,
avoiding reading, or getting headaches while reading should be evaluated. Problems with sustaining
focusing (accommodative insufficiency) or problems
keeping words single (convergence or divergence problems) may be present. A full eye-health evaluation and
vision training workup may reveal a problem. Vision
training is also appropriate for people learning how to
coordinate the eyes after surgery for strabismus. Vision
training can also be used in lazy eye (amblyopia) and
includes patching the eye and doing various exercises.
Dyslexia is a problem with following the flow of
words when reading. Often the order of letters or
words is reversed. It is a complex problem involving
the way the brain processes the stream of information
coming in from the eyes. While vision therapy is not a
treatment for dyslexia or learning disabilities, there
may be an underlying visual processing problem that
may be present. Vision therapy can be part of a multidisciplinary approach to treating learning disabilities.
Sports vision deals with visual performance in
sport-related activities. Protective eyewear is also a
large consideration when participating in sports.
Basketball, baseball, racquetball, and swimming (and
other sports as well) can all cause injury to the eyes.
Batting helmets with face shields, protective goggles
with polycarbonate lenses, or something as simple as
ultraviolet (UV) coatings on glasses to protect the eyes
from the sun in outdoor sports such as golf can protect
the eyes. Hitting a baseball or throwing a basketball
into a hoop requires accurate fixation. Golfers need to
see clearly and judge distance. Bifocals may need to be
adjusted to allow for putting, driving, and reading the
3920

score card. While many of these issues (e.g., UV coatings) can be addressed at a regular eye exam, sports
vision may be able to help with more specific, individual problems.

Precautions
Behavioral optometry is a relatively new field of
study. Results are mixed. Newer techniques, more
refined evaluation methods, and newer pieces of apparatus are continuously being appraised. More study
results are needed to define the scope and benefits of
this discipline.

Description
Vision therapy is individually tailored to the subject and the discovered problems. It can be a lengthy
process with many variations that requires repetition
until eye muscles, coordination, reflexes, habits, and
the way the brain handles visual input are all retrained.
Each program will be individualized. The patient
should be aware of the time involved for treatment.
Treatment can be from several weeks to several
months depending upon the condition. Some insurance plans may cover vision training.

Preparation
If vision therapy is recommended, the optometrist
will discuss thoroughly what is expected and necessary
for success. The patient must be prepared to perform
some eye exercises at home.

Aftercare
Even after the treatment is successful, it may be
necessary to continue the exercises to maintain the
benefits. It may be necessary to repeat treatment in
the future.

Risks
No risk is involved. The treatment is safe.

Normal results
A carefully and individually tailored program of
vision therapy should result in a gradual improvement
in whatever complex visual function is being
addressed. This progress ought to be measurable by
using the same tests that were used to diagnose it. If
the patient had symptoms, such as headaches or double vision while reading, it should be alleviated.
GALE ENCYCLOPEDIA OF MEDICINE

Accommodation—The focusing of the lens of the
eye.
Binocular—Both eyes accurately pointing to the
same object.
Stereopsis—The visual perception of depth, or
the ability to see three-dimensionally. For this to
occur, the person must be binocular.

Abnormal results
Because the treatment is safe, the only abnormal
result is failure. At the start of treatment, the optometrist should provide a reasonable estimate of what
improvement to expect and how long it will take.
Should this prove incorrect, either the treatment
needs to be modified or the problem deemed untreatable by that method.
Resources
ORGANIZATIONS

American Optometric Association. 243 North Lindbergh
Blvd., St. Louis, MO 63141. (314) 991-4100. <http://
www.aoanet.org>.
Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://
www.preventblindness.org>.

J. Ricker Polsdorfer, MD

Visual evoked potential study see Evoked
potential studies

Visual impairment
Definition
Total blindness is the inability to tell light from
dark, or the total inability to see. Visual impairment or
low vision is a severe reduction in vision that cannot be
corrected with standard glasses or contact lenses and
reduces a person’s ability to function at certain or all
tasks. Legal blindness (which is actually a severe visual
impairment) refers to a best-corrected central vision of
20/200 or worse in the better eye or a visual acuity of
better than 20/200 but with a visual field no greater
than 208 (e.g., side vision that is so reduced that it
appears as if the person is looking through a tunnel).
GALE ENCYCLOPEDIA OF MEDICINE

Vision is normally measured using a Snellen chart.
A Snellen chart has letters of different sizes that are
read, one eye at a time, from a distance of 20 ft. People
with normal vision are able to read the 20 ft line at 20
ft–20/20 vision–or the 40 ft line at 40 ft, the 100 ft line
at 100 ft, and so forth. If at 20 ft the smallest readable
letter is larger, vision is designated as the distance from
the chart over the size of the smallest letter that can be
read.
Eye care professionals measure vision in many
ways. Clarity (sharpness) of vision indicates how well
a person’s central visual status is. The diopter is the
unit of measure for refractive errors such as nearsightedness, farsightedness, and astigmatism and indicates
the strength of corrective lenses needed. People do not
just see straight ahead; the entire area of vision is
called the visual field. Some people have good vision
(e.g., see clearly) but have areas of reduced or no vision
(blind spots) in parts of their visual field. Others have
good vision in the center but poor vision around the
edges (peripheral visual field). People with very poor
vision may be able only to count fingers at a given
distance from their eyes. This distance becomes the
measure of their ability to see.
The World Health Organization (WHO) defines
impaired vision in five categories:


Low vision 1 is a best corrected visual acuity of 20/70.



Low vision 2 starts at 20/200.



Blindness 3 is below 20/400.



Blindness 4 is worse than 5/300



Blindness 5 is no light perception at all.



A visual field between 58 and 108 (compared with a
normal visual field of about 1208) goes into category
3; less than 58 into category 4, even if the tiny spot of
central vision is perfect.

Color blindness is the reduced ability to perceive
certain colors, usually red and green. It is a hereditary
defect and affects very few tasks. Contrast sensitivity
describes the ability to distinguish one object from
another. A person with reduced contrast sensitivity
may have problems seeing things in the fog because
of the decrease in contrast between the object and
the fog.
According to the WHO there are over forty million people worldwide whose vision is category 3 or
worse, 80% of whom live in developing countries. Half
of the blind population in the United States is over 65
years of age.
3921

Visual impairment

Description

KEY TERMS

Visual impairment

Causes and symptoms
The leading causes of blindness include:


macular degeneration



glaucoma



cataracts



diabetes mellitus

Other possible causes include infections, injury, or
nutrition.
Infections
Most infectious eye diseases have been eliminated
in the industrialized nations by sanitation, medication,
and public health measures. Viral infections are the
main exception to this statement. Some infections that
may lead to visual impairment include:


Herpes simplex keratitis. A viral infection of the
cornea. Repeated occurrences may lead to corneal
scarring.



Trachoma. This disease is responsible for six to nine
million cases of blindness around the world, of the
third of a billion who have the disease. Trachoma is
caused by an incomplete bacterium, Chlamydia trachomatis, that is easily treated with standard antibiotics. It is transmitted directly from eye to eye, mostly
by flies. The chlamydia gradually destroy the cornea.





Leprosy (Hansen’s disease). This is another bacterial
disease that has a high affinity for the eyes. It, too,
can be effectively treated with medicines.
River blindness. Much of the tropics of the Eastern
Hemisphere are infested with Onchocerca volvulus, a
worm that causes ‘‘river blindness.’’ This worm is
transmitted by fly bites and can be treated with a
drug called ivermectin. Nevertheless, twenty-eight
million people have the disease, and 40% of them
are blind from it.
Other causes

Exposure of a pregnant woman to certain diseases
(e.g., rubella or toxoplasmosis) can cause congenital
eye problems. Injuries to the eyes can result in blindness. Very little blindness is due to disease in the brain
or the optic nerves. Multiple sclerosis and similar nervous system diseases, brain tumors, diseases of the eye
sockets, and head injuries are rare causes of blindness.

xerophthalmia from this deficiency each year. Five
percent end up blind.

Diagnosis
A low vision exam is slightly different from a
general exam. While a case history, visual status, and
eye health evaluation are common to both exams,
some things do differ. Eye charts other than a
Snellen eye chart will be used. Testing distance will
vary. A trial frame worn by the patient is usually used
instead of the instrument containing the lenses the
patient sits behind (phoropter). Because the low vision
exam is slightly more goal oriented than a general
exam, for example, what specifically is the patient
having trouble with (reading, seeing street signs, etc.)
different optical and nonoptical aids will generally be
tried. Eye health is the last thing to be checked so that
the lights necessary to examine the eyes will not interfere with the rest of the testing.

Treatment
There are many options for patients with visual
impairment. There are optical and nonoptical aids.
Optical aids include:


Telescopes. May be used to read street signs.



Hand magnifiers. May be used to read labels on
things at the store.



Stand magnifiers. May be used to read.



Prisms. May be used to move the image onto a
healthy part of the retina in some eye diseases.



Closed circuit television (CCTV). For large magnification (e.g., for reading).

Nonoptical aids can include large print books and
magazines, check-writing guides, large print dials on
the telephone, and more.
For those who are blind, there are enormous
resources available to improve the quality of life. For
the legally blind, financial assistance for help may be
possible. Braille and audio books are increasingly
available. Guide dogs provide well-trained eyes and
independence. Orientation and mobility training is
available. There are special schools for blind children
and access to disability support through Social
Security and private institutions.

Nutrition
Vitamin A deficiency is a widespread cause of
corneal degeneration in children in developing
nations. As many as five million children develop
3922

Prognosis
The prognosis generally relates to the severity of
the impairment and the ability of the aids to correct it.
GALE ENCYCLOPEDIA OF MEDICINE

Cornea—The clear dome-shaped structure that is
part of the front of the eye. It lies in front of the
colored part of the eye (iris).
Diabetic retinopathy—Retinal disease caused by
the damage diabetes does to small blood vessels.
Phoropter—The instrument used to measure
refractive status of the eyes. It contains many lenses
which are then changed in front of the eyes while
the patient is looking at an eye chart. This is when
the doctor usually asks, ‘‘Which is better, one or
two?’’
Xerophthalmia—A drying of the cornea and
conjunctiva.

A good low vision exam is important to be aware of
the latest low vision aids.

Prevention
Regular eye exams are important to detect silent
eye problems (e.g., glaucoma). Left untreated, glaucoma can result in blindness.
Corneal infections can be treated with effective
antibiotics. When a cornea has become opaque
beyond recovery it must be transplanted. Good
hygiene (e.g., washing hands frequently) to prevent
infection, proper use of contact lenses, and not sharing
makeup are just some ways to guard against corneal
infections.
Cataracts should be removed when they interfere
with a person’s quality of life.
Primary prevention addresses the causes before
they ever begin. Fly control can be accomplished by
simple sanitation methods. Public health measures can
reduce the incidence of many infectious diseases.
Vitamin A supplementation (when appropriate) will
eliminate xerophthalmia completely. It is possible that
protecting the eyes against ultraviolet (UV) light will
reduce the incidence of cataracts, macular degeneration, and some other eye diseases. UV coatings can be
placed on regular glasses, sunglasses, and ski goggles.
Patients should ask their eye care professional about
UV coatings. Protective goggles should also be worn
in certain situations (e.g., certain jobs, sports, even
mowing the lawn).
Secondary prevention addresses treating established diseases before they cause irreversible eye
GALE ENCYCLOPEDIA OF MEDICINE

damage. Having general physical checkups can also
detect systemic diseases such as diabetes or high blood
pressure. Control of diabetes is very important in preserving sight.
Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.
American Foundation for the Blind. 11 Penn Plaza, Suite
300, New York, NY 10001. (800) 232-5463.
Guide Dogs for the Blind. P.O. Box 1200, San Rafael, CA
94915. (415) 499-4000.
International Eye Foundation. 7801 Norfolk Ave.,
Bethesda, MD 20814. (301) 986-1830.
Lighthouse National Center for Education. 111 E. 59th
Street. New York, NY 10022. (800) 334-5497.<http://
www.lighthouse.org>.
National Association for the Visually Handicapped. 22 West
21st St., New York, NY 10010. (212) 889-3141.
National Center for Sight. (800) 221-3004.
National Children’s Eye Care Foundation. One Clinic
Center, A3-108, Cleveland, OH 44195. (216) 444-0488.
National Eye Institute. 2020 Vision Place, Bethesda, MD
20892-3655. (301) 496-5248. <http://
www.nei.nih.gov>.
National Federation of the Blind. 1800 Johnson St.,
Baltimore, MD 21230. (301) 569-9314.
Prevent Blindness America. 500 East Remington Road,
Schaumburg, IL 60173. (800) 331-2020. <http://
www.preventblindness.org>.
Research to Prevent Blindness. 598 Madison Ave., New
York, NY 10022. (212) 363-3911.

J. Ricker Polsdorfer, MD

Visualization see Guided imagery

Vitamin A deficiency
Definition
Vitamin A deficiency exists when the chronic failure to eat sufficient amounts of vitamin A or betacarotene results in levels of blood-serum vitamin A
that are below a defined range. Beta-carotene is a
form of pre-vitamin A, which is readily converted to
vitamin A in the body. Night blindness is the first
symptom of vitamin A deficiency. Prolonged and
severe vitamin A deficiency can produce total and
irreversible blindness.
3923

Vitamin A deficiency

KEY TERMS

Vitamin A deficiency

Description
Vitamin A (called retinol in mammals) is a fatsoluble vitamin. The recommended dietary allowance (RDA) for vitamin A is 1.0 mg/day for the
adult man and 0.8 mg/day for the adult woman.
Since beta-carotene is converted to vitamin A in
the body, the body’s requirement for vitamin A
can be supplied entirely by beta-carotene. Six mg
of beta-carotene are considered to be the equivalent
of 1 mg of vitamin A. The best sources of vitamin A
are eggs, milk, butter, liver, and fish, such as herring, sardines, and tuna. Beef is a poor source of
vitamin A. Plants do not contain vitamin A, but
they do contain beta-carotene and other carotenoids. The best sources of beta-carotene are darkgreen, orange, and yellow vegetables; spinach, carrots, oranges, and sweet potatoes are excellent
examples. Cereals are poor sources of betacarotene.
Vitamin A is used for two functions in the body.
Used in the eye, it is a component of the eye’s lightsensitive parts, containing rods and cones, that
allow for night-vision or for seeing in dim-light circumstances. Vitamin A (retinol) occurs in the rods.
Another form of Vitamin A, retinoic acid, is used
in the body for regulating the development of various tissues, such as the cells of the skin, and the lining
of the lungs and intestines. Vitamin A is important
during embryological development, since, without
vitamin A, the fertilized egg cannot develop into a
fetus.

Causes and symptoms
Vitamin A deficiency occurs with the chronic
consumption of diets that are deficient in both vitamin A and beta-carotene. When vitamin A deficiency
exists in the developed world, it tends to happen
in alcoholics or in people with diseases that affect
the intestine’s ability to absorb fat. Examples of
such diseases are celiac disease (chronic nutritional
disorder), cystic fibrosis, and cholestasis (bile-flow
failure or interference). Vitamin A deficiency occurred
in infants during the early 1900s in Denmark. The
deficiency resulted when milk fat was made into
butter for export, leaving the by-product (skimmed
milk) for infant feeding. Vitamin A deficiency has
taken place in infants in impoverished populations
in India, where the only foods fed to the infants
were low in beta-carotene. Vitamin A deficiency is
also common in areas like Southeast Asia, where
polished rice, which lacks the vitamin, is a major
part of the diet.
3924

KEY TERMS
Bitot’s spots—Bitot’s spots are superficial, foamy
gray, triangular spots on the white of the
eyeball.
Carotenoids—Carotenoids are yellow to deep-red
pigments.
Conjunctiva—The conjunctiva is a clear layer of
cells that covers the eye and directly contacts the
atmosphere. The conjunctiva is about five-cells
thick.
Cornea—The cornea is a clear layer of cells that
covers the eye, just under the conjunctiva. The
cornea is about 50-cells thick.
Fat-soluble vitamin—Fat-soluble vitamins can be
dissolved in oil or in melted fat. Water-soluble
vitamins can be dissolved in water or juice.
Keratomalacia—Keratomalacia is ulceration of the
cornea.
Recommended Dietary Allowance (RDA)—The
Recommended Dietary Allowances are quantities
of nutrients in the diet that are required to maintain
good health in people. RDAs are established by the
Food and Nutrition Board of the National Academy
of Sciences, and may be revised every few years.
A separate RDA value exists for each nutrient.
The RDA values refer to the amount of nutrient
expected to maintain good health in people. The
actual amounts of each nutrient required to maintain good health in specific individuals differ from
person to person.
Xerophthalmia—Xerophthalmia is a dry, thickened, lusterless condition of the eyeball resulting
from vitamin A deficiency.

The earliest symptom of vitamin A deficiency
is night blindness. Prolonged deficiency results in
drying of the conjunctiva (the mucous membrane
that lines the inner surface of the eyelids and
extends over the forepart of the eyeball). With
continued vitamin A deficiency, the drying extends
to the cornea (xerophthalamia). The cornea eventually shrivels up and becomes ulcerated (keratinomalacia). Superficial, foamy gray triangular spots
may appear in the white of the eye (Bitot’s spots).
Finally, inflammation and infection occur in the
interior of the eye, resulting in total and irreversible blindness.
GALE ENCYCLOPEDIA OF MEDICINE

Vitamin A status is measured by tests for retinol.
Blood-serum retinol concentrations of 30-60 mg/dl
are considered in the normal range. Levels that fall
below this range indicate vitamin A deficiency. Night
blindness is measured by a technique called electroretinography. Xerophthalamia, keratinomalacia, and
Bitot’s spots are diagnosed visually by trained medical
personnel.

Vitamin B6 deficiency
Definition
Vitamin B6 is used by the body as a catalyst in
reactions that involve amino acids. Vitamin B6 deficiency is rare, since most foods eaten contain the
vitamin.

Description
Treatment
Vitamin A deficiency can be prevented or treated
by taking vitamin supplements or by getting injections
of the vitamin. The specific doses given are oral retinyl
palmitate (110 mg), retinyl acetate (66 mg), or injected
retinyl palmitate (55 mg) administered on each of two
successive days, and once a few weeks later if symptoms are not relieved.

Prognosis
The prognosis for correcting night blindness is
excellent. Xerophthalamia can be corrected with vitamin A therapy. Ulcerations, tissue death, and total
blindness, caused by severe vitamin A deficiency, cannot be treated with vitamin A.

Prevention
Vitamin A deficiency can be prevented by including foods rich in vitamin A or beta-carotene as a
regular component of the diet; liver, meat, eggs,
milk, and dairy products are examples. Foods rich
in beta-carotene include red peppers, carrots, pumpkins, as well as those just mentioned. Margarine is rich
in beta-carotene, because this chemical is used as a
coloring agent in margarine production. In Africa,
Indonesia, and the Philippines, vitamin A deficiency
is prevented by public health programs that supply
children with injections of the vitamin.
Resources
BOOKS

Brody, T. Nutritional Biochemistry. San Diego: Academic
Press, Inc., 1998.

Tom Brody, PhD

Vitamin B1 see Beriberi

Vitamin B6 is a water-soluble vitamin. The recommended dietary allowance (RDA) for vitamin B6 is 2.0
mg/day for the adult man and 1.6 mg/day for the adult
woman. Vitamin B6 in the diet generally occurs as a
form called pyridoxal phosphate. In this form, it cannot be absorbed by the body. During the process of
digestion, the phosphate group is removed, and pyridoxal is produced. However, the body readily absorbs
pyridoxal, and converts it back to the active form of
the vitamin (pyridoxal phosphate).
Poultry, fish, liver, and eggs are good sources of
vitamin B6, comprising about 3-4 mg vitamin/kg food;
meat and milk contain lesser amounts of the vitamin.
The vitamin also occurs, at about half this level, in a
variety of plant foods, including beans, broccoli, cabbage, and peas. Vitamin B6 tends to be destroyed with
prolonged cooking, with storage, or with exposure to
light.
As mentioned, vitamin B6 takes various forms.
One of these forms, called pyridoxine, is relatively
stable. For this reason, pyridoxine is the form of vitamin B6 that is used in vitamin supplements, or when
foods are fortified. Apples and other fruits are poor
sources of the vitamin, containing only 0.2-0.6 mg
vitamin/kg food.
Vitamin B6, used mainly in the body for the processing of amino acids, performs this task along with
certain enzymes. The enzyme that participates in this
type of complex is aminotransferase. Several types of
aminotransferase exist. With vitamin B6 deficiency,
while aminotransferase continues to occur in the various organs of the body, there is an abnormally low
level of the active vitamin B6/aminotransferase complex present. Thus, this vitamin deficiency results in
the impairment of a variety of activities in the body.
With supplement correction of the vitamin B6 deficiency, the aminotransferase then readily forms the
active complex, and normal metabolism is restored.

Vitamin B2 deficiency see Riboflavin
deficiency

Vitamin B6 converts certain amino acids (glutamic
acid, aspartic acid, glycine) to energy. This allows the
body to process all dietary protein, even when the

GALE ENCYCLOPEDIA OF MEDICINE

3925

Vitamin B6 deficiency

Diagnosis

Vitamin B6 deficiency

KEY TERMS
Amino acid—Amino acids are small molecules that
are used as building blocks for all proteins. Some
amino acids are also used in the body for the manufacture of hormones. There are about 20 nutritionally important amino acids, including glutamic
acid, glycine, methionine, lysine, tryptophan, serine, and glycine.
Fat-soluble vitamins—Fat-soluble vitamins can be
dissolved in oil or in melted fat.
Recommended Dietary Allowance (RDA)—The
Recommended Dietary Allowances (RDAs) are
quantities of nutrients in the diet that are required
to maintain good health in people. RDAs are established by the Food and Nutrition Board of the
National Academy of Sciences, and may be revised
every few years. A separate RDA value exists for
each nutrient. The RDA values refer to the amount
of nutrient expected to maintain good health in
people. The actual amounts of each nutrient
required to maintain good health in specific individuals differ from person to person.
Water-soluble vitamins—Water-soluble vitamins
can be dissolved in water or juice.

dietary protein is in excess of the body’s needs.
Vitamin B6 also allows the body to synthesize certain
amino acids. For example, if the diet is deficient or low
in certain amino acids, such as glycine or serine, vitamin B6 enables the body to make them from sugar.
Vitamin B6 is used also for the synthesis of certain
hormones, such as adrenaline.

Causes and symptoms
Vitamin B6 deficiency occurs rarely. When it does,
it is usually associated with poor absorption of nutrients in the gastrointestinal tract (as in alcoholism, or
with chronic diarrhea), the taking of certain drugs (as
isoniazid, hydrolazine, penicillamine) that inactivate
the vitamin, with genetic disorders that inhibit metabolism of the vitamin, or in cases of starvation.
The symptoms of vitamin B6 deficiency in adults
are only vaguely defined. These include nervousness,
irritability, insomnia, muscle weakness, and difficulty
in walking. Vitamin B6 deficiency may produce fissures and cracking at the corners of the mouth. The
deficiency occurred in infants fed early versions of
commercial canned infant formula, when the vitamin
3926

had been inadvertently omitted from the formula. This
error resulted in infants failing to grow, in irritability,
and in seizures.

Diagnosis
Vitamin B6 status is measured by the transaminase stimulation test. This test requires extraction of
red blood cells, and placement of the cells in two test
tubes. Special chemicals (reagents) are added to both
test tubes to allow for measurement of aminotransferase. This enzyme requires pyridoxal phosphate. A
known quantity of pure pyridoxal phosphate is
added to one of the test tubes. The activity level of
the enzyme is measured, and compared, in both test
tubes. If the added pyridoxal phosphate did not stimulate activity, the patient is considered not to be
deficient in vitamin B6. Neither is the patient considered deficient if only slight stimulation occurred. But if
a stimulation of four-fold or more occurred, a vitamin
B6 deficiency is present.

Treatment
Vitamin B6 deficiency can be prevented or treated with consumption of the recommended dietary
allowance, as supplied by food or by vitamin
supplements.

Prognosis
The prognosis for correcting vitamin B6 deficiency
is excellent.

Prevention
Vitamin B6 deficiency is not a major concern for
most people. The deficiency can be prevented with
consumption of a mixed diet that includes poultry,
fish, eggs, meat, vegetables, and grains.
Resources
BOOKS

Brody, T. Nutritional Biochemistry. San Diego: Academic
Press, Inc., 1998.

Tom Brody, PhD

Vitamin B12 deficiency anemia see
Pernicious anemia
Vitamin C deficiency see Scurvy
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Vitamin D deficiency exists when the concentration of 25-hydroxy-vitamin D (25-OH-D) in the blood
serum occurs at 12 ng/ml (nanograms/milliliter), or
less. The normal concentration of 25-hydroxy-vitamin
D in the blood serum is 25-50 ng/ml. When vitamin D
deficiency continues for many months in growing children, the disease commonly referred to as rickets will
occur. A prolonged deficiency of the vitamin in adults
results in osteomalacia. Both diseases involve defects
in bones.

Description
Vitamin D is a fat-soluble vitamin, meaning it is
able to be dissolved in fat. While some vitamin D is
supplied by the diet, most of it is made in the body. To
make vitamin D, cholesterol, a sterol that is widely
distributed in animal tissues and occurs in the yolk of
eggs, as well as in various oils and fats, is necessary.
Once cholesterol is available in the body, a slight alteration in the cholesterol molecule occurs, with one change
taking place in the skin. This alteration requires the
energy of sunlight (or ultraviolet light). Vitamin D
deficiency, as well as rickets and osteomalacia, tends
to occur in persons who do not get enough sunlight and
who fail to eat foods that are rich in vitamin D.
Once consumed, or made in the body, vitamin D is
further altered to produce a hormone called 1,25-dihydroxy-vitamin D (1,25-diOH-D). The conversion of
vitamin D to 1,25-diOH-D does not occur in the
skin, but in the liver and kidney. First, vitamin D is
converted to 25-OH-D in the liver; it then enters the
bloodstream, where it is taken-up by the kidneys. At
this point, it is converted to 1,25-diOH-D. Therefore,
the manufacture of 1,25-diOH-D requires the participation of various organs of the body—the liver, kidney, and skin.
The purpose of 1,25-diOH-D in the body is to
keep the concentration of calcium at a constant level
in the bloodstream. The maintenance of calcium at
a constant level is absolutely required for human life
to exist, since dissolved calcium is required for nerves
and muscles to work. One of the ways in which 1,25diOH-D accomplishes this mission is by stimulating
the absorption of dietary calcium by the intestines.
The sequence of events that can lead to vitamin D
deficiency, then to bone disease, is as follows: a lack of
vitamin D in the body creates an inability to
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
Vitamin D deficiency can be caused by conditions
that result in little exposure to sunlight. These conditions include: living in northern countries; having dark
skin; being elderly or an infant, and having little
chance to go outside; and covering one’s face and
body, such as for religious reasons. Many Arab
women cover the entire body with black cloth, and
wear a veil and black gloves when they go outside.
These women may acquire vitamin D deficiency, even
though they live in a sunny climate.
Most foods contain little or no vitamin D. As a
result, sunshine is often a deciding factor in whether
vitamin D deficiency occurs. Although fortified milk
and fortified infant formula contain high levels of
vitamin D, human breast milk is rather low in the
vitamin. The term fortified means that vitamins are
added to the food by the manufacturer.
To say that a food is high or low in vitamin D
means how much of that food needs to be eaten in
order to prevent vitamin deficiency and maintain good
health. An exact meaning can be provided by comparing the Recommended Dietary Allowance
of vitamin D with the amount of vitamin D supplied
by a particular food per day. The Recommended
Dietary Allowance, also referred to as RDA, is a
recommendation based on data derived from different
population groups and ages. The RDA for vitamin D
for adults is 200 International Units (IU) per day, and
can be supplied by eating approximately 1.5 kg of beef,
2.0 kg of corn oil, or 100 kg of cabbage. Few people,
though, would want to eat a kilogram of beef in one
day, and no human being is capable of eating 100 kg of
cabbage in a day; therefore, these foods are poor
sources of vitamin D. However, saltwater fish such
as salmon, herring, and sardines are rich in vitamin
D, supplied from the oils produced by these fish. The
RDA can also be supplied by eating roughly 50 g of
salmon or 2.0 g of cod liver oil, and since fortified milk
contains 400 IU per quart, half a quart of milk provides the RDA. For comparison, human breast milk
contains only 4 to 60 IU per quart.
No harm is likely to result from vitamin D deficiency that occurs for only a few days a year. If the
3927

Vitamin D deficiency

Vitamin D deficiency

manufacture 1,25-diOH-D, which results in decreased
absorption of dietary calcium and increased loss of
calcium in the feces. When this happens, the bones
are affected. Vitamin D deficiency results in a lack of
bone mineralization (calcification) in growing persons, or in an increased demineralization (decalcification) of bone in adults.

Vitamin D deficiency

deficiency occurs for a period of many months or
years, however, rickets or osteomalacia may develop.
The symptoms of rickets include bowed legs and
bowed arms. The bowed appearance is due to the
softening of bones, and their bending if the bones are
weight-bearing. Bone growth occurs through the creation of new cartilage, a soft substance at the ends
of bones. When the mineral calcium phosphate is
deposited onto the cartilage, a hard structure is created. In vitamin D deficiency, though, calcium is
not available to create hardened bone, and the result
is soft bone. Other symptoms of rickets include particular bony bumps on the ribs called rachitic rosary
(beadlike prominences at the junction of the ribs
with their cartilages) and knock-knees. Seizures
may also occasionally occur in a child with rickets,
because of reduced levels of dissolved calcium in the
bloodstream.
Although osteomalacia is rare in the United
States, symptoms of this disease include reduced bone
strength, an increase in bone fractures, and sometimes
bone pain, muscle weakness, and a waddling walk.

Diagnosis
Vitamin D deficiency is diagnosed by measuring
the level of 25-hydroxy-vitamin D in the blood serum.
The normal level or concentration of this form of the
vitamin ranges from 25-50 ng/ml. Deficiency occurs
when this level decreases to about 12 ng/ml or less. As
mentioned previously, 25-OH-D is not the active form
of the vitamin. It must be converted to 1,25-diOH-D in
order to cause responses in various organs of the body.
However, the levels of vitamin D, or of 1,25-dihydroxy-vitamin D in the blood, do not give a reliable
picture of whether a person is deficient in the vitamin.
For this reason, they are not measured when testing
for vitamin D deficiency.
Rickets is diagnosed by x-ray examination of leg
bones. A distinct pattern of irregularities, abnormalities, and a coarse appearance can be clearly seen with
rickets. Osteomalacia is also diagnosed with x-ray
examination. Measurements of blood plasma 25-OHD, blood plasma calcium, and blood plasma parathyroid hormone must also be obtained for the diagnosis
of these diseases. Parathyroid hormone and 1,25diOH-D work together in the body to regulate the
levels of calcium in the blood.

Treatment
Rickets heals promptly with 4,000 IU of oral
vitamin D per day administered for approximately
3928

one month. During this treatment, the doctor
should monitor the levels of 25-OH-D in the plasma
to make certain they are raised to a normal value.
The bone abnormalities (visible by x ray) generally
disappear gradually over a period of 3-9 months.
Parents are instructed to take their infants outdoors
for approximately 20 minutes per day with their
faces exposed. Children should also be encouraged
to play outside. Foods that are good sources of
vitamin D include cod liver oil, egg yolks, butter,
and oily fish. Some foods, including milk and
breakfast cereals, are also fortified with synthetic
vitamin D.
Osteomalacia is treated by eating 2,500 IU per day
of vitamin D for about three months. Measurements
of 25-OH-D, calcium, and parathyroid hormone
should be obtained after the treatment period to
make sure the therapy did, in fact, result in normal
blood values.
Care must be taken in treating vitamin D deficiency, since high doses of vitamin D are toxic and
can result in the permanent deposit of minerals in the
heart, lungs, and kidneys. Symptoms of toxicity are
nausea, vomiting, pain in joints, and lack of interest in
eating food. In adults, vitamin D toxicity occurs with
eating 50,000 IU or more per day. In infants, toxicity
occurs with 1,000 IU per day. The continued intake of
toxic doses results in death.
Rickets and osteomalacia are almost always treated with oral supplements of vitamin D, with the
recommendation to acquire daily exposure to direct
sunlight. An alternative to sunlight is the use of an
ultraviolet (UV) lamp. When using UV lamps, the eyes
must be covered to protect them against damage.
Many types of sunglasses allow UV light to pass
through, so only those that are opaque to UV light
should be used. Attempts to acquire sunlight through
glass windows fail to help the body make vitamin D.
This is because UV light does not pass through window glass.
Rickets may also occur with calcium deficiency,
even when a child is regularly exposed to sunshine.
This type of rickets has been found in various parts of
Africa. The bone deformities are similar to, or are the
same as, those that occur in typical rickets; however,
calcium deficiency rickets is treated by increasing the
amount of calcium in the diet. No amount of vitamin
D can cure the rickets of a child with a diet that is
extremely low in calcium. For this reason, it is recommended that calcium be given in conjunction with
vitamin D supplementation.
GALE ENCYCLOPEDIA OF MEDICINE

25-hydroxy-vitamin D—This is the form of vitamin
D that is measured in order to assess vitamin D
deficiency.
Cholesterol—A fat-soluble steroid alcohol (sterol)
found in animal fats and oils, and in egg yolks. The
human body needs cholesterol to produce vitamin
D.
Fat-soluble vitamin—A vitamin that dissolves
easily in fat or oil, but not in water. The fat-soluble
vitamins are vitamins D, E, A, and K.
International unit (IU)—A measurement of biological activity in which one IU is equal to one mg
(milligram).
Osteomalacia—Osteomalacia is a bone disease
that occurs in adults and is caused by a prolonged
period of vitamin D deficiency.

people, a 400 IU supplement may not be enough to
result in the normal absorption of calcium; therefore,
daily doses of 10,000 IU per day may be needed. For
infants who are fed only breast milk (and rarely
exposed to sunshine), a daily supplement of 200-300
IU is recommended.
Rickets continues to be a problem in Africans and
Asian Indians who migrate to Canada or Great
Britain, especially where these immigrants do not
drink fortified milk. Prevention of rickets in these
populations is attempted through educational programs sponsored by the government.
Resources
PERIODICALS

Kinyamu, H., et al. ‘‘Serum Vitamin D Metabolites and
CalciumAbsorption in Normal Young and Elderly
Free-Living Women and in Women Living in Nursing
Homes.’’ American Journal of Clinical Nutrition 65
(1997): 790-797.

Rachitic rosary—Beadlike bumps present at the
junction of the ribs with their cartilages–often
seen in children with rickets.
Recommended Dietary Allowance (RDA)—The
amount of nutrients, including vitamins, that
should be supplied by foods on a daily basis to
maintain normal health. Recommendations are
based on data obtained from different population
groups and ages.
Rickets—Rickets is a bone disease that occurs in
infants and growing children and is caused by a
prolonged period of vitamin D deficiency.

Prognosis
The prognoses for correcting vitamin D deficiency, rickets, and osteomalacia are excellent.
Vitamin D treatment results in the return of bone
mineralization to a normal rate, the correction of low
plasma calcium levels, the prevention of seizures, and
a recovery from bone pain. On the other hand, deformities such as bowed legs and the rachitic rosary persist throughout adult life.

Prevention
Food fortification has almost completely eliminated rickets in the United States. Vitamin D deficiency can be prevented by acquiring the RDA
through drinking fortified milk and eating fortified
cereals. For those who cannot drink milk, supplements of pills might be considered. In some older
GALE ENCYCLOPEDIA OF MEDICINE

Tom Brody, PhD

Vitamin E deficiency
Definition
Vitamin E deficiency is a very rare problem that
results in damage to nerves. When vitamin E deficiency does occur, it strikes people with diseases that
prevent the absorption of dietary fats and fat-soluble
nutrients. Since vitamin E is a fat-soluble vitamin, it
has some of the properties of fat.

Description
The recommended dietary allowance (RDA) for
vitamin E is 10 mg/day for the adult man, 10 mg/day
for the adult woman, and 3 mg/day for the infant.
Vitamin E occurs in foods in a variety of related
forms. The most potent and useful form of vitamin E
is called alpha-tocopherol. The best sources of vitamin
E are vegetable oils, such as corn oil, soy oil, and peanut oil. Animal fats, such as butter and lard, contain
lower levels of the vitamin. Corn oil contains about 16
mg of alpha-tocopherol per 100 g oil. Wheat-germ oil
contains 120 mg alpha-tocopherol per 100 g oil. Fish,
eggs, and beef contain relatively low levels of the vitamin, with about 1 mg per 100 g food.
Vitamin E seems to have only one function in the
body: the prevention of the natural and continual
3929

Vitamin E deficiency

KEY TERMS

Vitamin E deficiency

process of deterioration of all body tissues. This deterioration is provoked by a number of causes; one of
these is toxic oxygen. During the body’s metabolism of
atmospheric oxygen, toxic oxygen is produced continuously in the body by the formation of by-products.
These toxic by-products include hydrogen peroxide,
superoxide, and hypochlorite.
Hypochlorite is a natural product, produced by
cells of the immune system. It is also the active
component of bleach. Once formed, toxic oxygen
can damage various parts of the body, such as the
membranes which form the boundaries of every cell.
Vitamin E serves the body in protecting membranes
from toxic oxygen damage. In contrast, vitamin C
serves to protect the aqueous, or watery, regions of
the cell from toxic oxygen damage. The membranes
that are most sensitive to toxic oxygen damage are
the membranes of nerves; therefore, the main symptom of vitamin E deficiency is damage to the nervous
system.

Causes and symptoms
As mentioned, when vitamin E deficiency occurs,
it strikes people with diseases that prevent the absorption of dietary fats and fat-soluble nutrients. These
diseases include cystic fibrosis, pancreatitis,
and cholestasis (bile-flow obstruction). Bile salts,
produced in the liver, are required for the absorption
of fats. Cholestasis causes a decrease in the formation of bile salts and the consequent failure of
the body to absorb dietary fats. For this reason, this
disease may result in vitamin E deficiency. Premature
infants may be at risk for vitamin E deficiency
because they may be born with low tissue levels of
the vitamin, and because they have a poorly developed capacity for absorbing dietary fats. Infants suffering from fat-malabsorption diseases can develop
symptoms of vitamin E deficiency by age two. In
adults, the onset of a fat-malabsorption disease can
provoke vitamin E deficiency after a longer period, as
an example, ten years.
Patients with colorectal cancer caused by the socalled Ki-ras mutation have also been shown to
absorb less vitamin E from their diet than either
normal control subjects or cancer patients without
the mutation. The relationship between genetic
mutations and dietary factors requires more intensive
study.
Vitamin E deficiency in humans results in ataxia
(poor muscle coordination with shaky movements),
decreased sensation to vibration, lack of reflexes,
and paralysis of eye muscles. One particularly severe
3930

symptom of vitamin E deficiency is the inability
to walk.
Another symptom of early vitamin E deficiency
in children with cystic fibrosis is a decline in cognitive function, which results in difficulty with reading and falling behind in other intellectual skills
during the elementary school years. Researchers
have urged the introduction of neonatal screening
in order to offset the potential effects of early vitamin E deficiency.
More recently, the suggestion has been made that
vitamin E deficiency may be involved in the development of partial open-angle glaucoma (POAG), an
eye disorder whose causes are not fully understood as
of the early 2000s. The possibility that POAG is a
vitamin-deficiency disorder, however, needs further
research.

Diagnosis
Vitamin E status is measured by assessment of the
content of alpha-tocopherol in the blood plasma,
using a method called high-pressure liquid chromatography. Blood plasma levels of alpha-tocopherol that
are 5.0 mg/l, or above, indicate normal vitamin E
status; levels below 5.0 mg/l indicate vitamin E
deficiency.

Treatment
Vitamin E deficiency that occurs with cholestatic
liver disease or other malabsorption syndromes can be
treated with weekly injections of 100 mg alpha-tocopherol that may continue for six months. Vitamin E
deficiency in premature infants may require treatment
for only a few weeks.

Prognosis
The prognosis for correcting the neurological
symptoms of vitamin E deficiency is fair to excellent.

Prevention
The prevention of vitamin E deficiency should not
be a concern for most people, since the vitamin is
found in a wide variety of foods. Attention has been
given to the theory that vitamin E serves to protect
against cancer and atherosclerosis. The evidence that
normal levels of vitamin E protect against atherosclerosis is fairly convincing. However, there is little
or no proof that vitamin E intake, above and beyond
the recommended daily allowance (RDA), can prevent
cancer or atherosclerosis.
GALE ENCYCLOPEDIA OF MEDICINE

Fat-soluble vitamin—Fat-soluble vitamins can be
dissolved in oil or in melted fat.
Recommended dietary allowance (RDA)—The
quantity of a given nutrient in the diet that is
required to maintain good health in people.
RDAs are established by the Food and Nutrition
Board of the National Academy of Sciences, and
may be revised every few years. A separate RDA
value exists for each nutrient. The RDA values
refer to the amount of nutrient expected to maintain good health in people. The actual amounts
of each nutrient required to maintain good health
in specific individuals differ from person to
person.
Toxic oxygen—Oxygen is required for life, as it is
needed for energy production. When oxygen is
used by the body, most of it is converted to water.
However, a small fraction of the oxygen breathed is
converted to toxic oxygen. The body uses several
different processes for preventing and repairing
toxic-oxygen damage. One of these processes
involves vitamin E.
Water-soluble vitamins—Water-soluble vitamins
can be dissolved in water or juice.

Vitamin K deficiency
Definition
Vitamin K deficiency exists when chronic failure
to eat sufficient amounts of vitamin K results in a
tendency for spontaneous bleeding or in prolonged
and excessive bleeding with trauma or injury.
Vitamin K deficiency occurs also in newborn infants,
as well as in people treated with certain antibiotics. The
protein in the body most affected by vitamin K deficiency is a blood-clotting protein called prothrombin.

Description
Vitamin K is a fat-soluble vitamin. The recommended dietary allowance (RDA) for vitamin K is 80
mg/day for the adult man, 65 mg/day for the adult
woman, and 5 mg/day for the newborn infant. The
vitamin K present in plant foods is called phylloquinone; while the form of the vitamin present in animal
foods is called menaquinone. Both of these vitamins
are absorbed from the diet and converted to an active
form called dihydrovitamin K.
Spinach, lettuce, broccoli, brussels sprouts, and
cabbage are good sources of vitamin K, containing
about 8 mg vitamin K/kg food. Cow milk is also a
good source of the vitamin.
A portion of the body’s vitamin K is supplied by
bacteria living in the intestine rather than by dietary
sources.

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Vitamin E Deficiency.’’ Section 7, Chapter 86. In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Koscik, R. L., P. M. Farrell, M. R. Kosorok, et al.
‘‘Cognitive Function of Children with Cystic Fibrosis:
Deleterious Effect of Early Malnutrition.’’ Pediatrics
113 (June 2004): 1549–1558.
Laso, N., S. Mas, M. Jose Lafuente, et al. ‘‘Decrease in
Specific Micronutrient Intake in Colorectal Cancer
Patients with Tumors Presenting Ki-ras Mutation.’’
Anticancer Research 24 (May-June 2004): 2011–2020.
Veach, J. ‘‘Functional Dichotomy: Glutathione and Vitamin
E in Homeostasis Relevant to Primary Open-Angle
Glaucoma.’’ British Journal of Nutrition 91 (June 2004):
809–829.

Tom Brody, PhD
Rebecca J. Frey, PhD
GALE ENCYCLOPEDIA OF MEDICINE

Vitamin K plays an important role in blood clotting. Without the vitamin, even a small cut would
cause continuous bleeding in the body, and death.
Blood clotting is a process that begins automatically
when any injury produces a tear in a blood vessel. The
process of blood clotting involves a collection of molecules, which circulate continuously through the bloodstream. When an injury occurs, these molecules
rapidly assemble and form the blood clot. The clotting
factors are proteins, and include proteins called Factor
II, Factor VII, Factor IX, and Factor X. Factor II is
also called prothrombin. These proteins require vitamin K for their synthesis in the body. The bloodclotting process also requires a dozen other proteins
that do not need vitamin K for their synthesis.

Causes and symptoms
Newborns are especially prone to vitamin K deficiency. A nursing-mother’s milk is low in the vitamin;
breast milk can supply only about 20% of the infant’s
requirement. Infants are born with low levels of
3931

Vitamin K deficiency

KEY TERMS

Vitamin K deficiency

KEY TERMS
Fat-soluble vitamin—Fat-soluble vitamins can be
dissolved in oil or in melted fat.
Hemorrhage—Bleeding that continues for an
abnormally long period of time.
Phylloquinone—An alternate name for vitamin K1.
Prothrombin—Prothrombin is a blood-clotting
protein. Injury to a blood vessel produces a signal
which triggers the conversion of prothrombin to
thrombin. Thrombin is a protein which plays a
central role in provoking the assembly of other
proteins to form the blood clot.
Recommended Dietary Allowance (RDA)—The
Recommended Dietary Allowances (RDAs) are
quantities of nutrients in the diet that are required
to maintain good health in people. RDAs are established by the Food and Nutrition Board of the
National Academy of Sciences, and may be revised
every few years. A separate RDA value exists for
each nutrient. The RDA values refer to the amount
of nutrient expected to maintain good health in
people. The actual amounts of each nutrient
required to maintain good health in specific individuals differ from person to person.
Water-soluble vitamins—Water-soluble vitamins
can be dissolved in water or juice.

vitamin K in their body; they do not have any vitamin
K-producing bacteria in their intestines. Their digestive tracts are sterile. As a result, a form of vitamin K
deficiency, called hemorrhagic disease of the newborn,
may develop. This disease involves spontaneous bleeding beneath the skin or elsewhere in the infant’s body,
and occurs in about 1% of all infants. In rare cases, it
causes death due to spontaneous bleeding in the brain.
Vitamin K deficiency in adults is rare. When it
occurs, it is found in people with diseases that prevent
the absorption of fat. These diseases include cystic
fibrosis, celiac disease, and cholestasis. Vitamin K deficiency can exist in adults treated with antibiotics that
kill the bacteria that normally live in the digestive
tract. As mentioned, the intestine-bacteria supply
part of our daily requirement of vitamin K. Vitamin
K deficiency can result in bleeding gums, and in skin
that is easily bruised.
Others who may benefit from supplemental vitamin K include those taking medications that interact
with it or deplete the supply. It also appears to have
3932

some effectiveness in preventing osteoporosis, but
some studies done involved patients using a high dietary intake of the vitamin rather than supplements. In
2003, however, a group of Japanese researchers
reported that supplemental doses of vitamin K2 given
together with vitamin D3 appeared to reduce bone
turnover and sustain bone density in postmenopausal
women with mild osteoporosis.
Chronically low levels of vitamin K are correlated
with higher risk of hip fracture in older men and
women. A study done in 2003 reported that the current
recommended dietary intake for vitamin K in adults
may not be adequate for older women.

Diagnosis
Vitamin K status is measured by the prothrombin
time test. The normal prothrombin time is about 13
seconds. With vitamin K deficiency, the prothrombin
time can be several minutes. The test involves taking a
sample of blood, placing it in a machine called a
fibrometer, and measuring the time it takes for
blood-clot formation. Blood-clotting problems can
also be caused by a rare genetic disease called hemophilia. Hemophilia is not related to vitamin K deficiency. Once vitamin K deficiency is suspected, further
tests must be used to distinguish it from possible
hemophilia. Where a bleeding disorder can be corrected by vitamin K treatment, the diagnosis of vitamin K deficiency is proven to be correct.

Treatment
Vitamin K deficiency in newborn infants is treated
and prevented with a single injection of phylloquinone
(5 mg). Adults with vitamin K deficiency are treated
with daily oral doses of 10 mg phylloquinone for one
week.

Prognosis
The prognosis for correcting vitamin K deficiency, and associated blood-clotting problems, is
excellent.

Prevention
Aside from newborns and young infants, vitamin
K deficiency is not a concern for the general population. Vitamin K deficiency can be prevented by assuring that the diet contains such foods as spinach,
cabbage, brussels sprouts, and eggs. Soybean oil,
canola oil, and olive oil are good sources of the vitamin, while corn oil and peanut oil are very poor
GALE ENCYCLOPEDIA OF MEDICINE

Resources
BOOKS

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part I: Food for Thought. New York: Simon &
Schuster, 2002.
PERIODICALS

American Academy of Pediatrics Committee on Fetus and
Newborn. ‘‘Controversies Concerning Vitamin K and
the Newborn. American Academy of Pediatrics
Committee on Fetus and Newborn.’’ Pediatrics 112, no.
1, Part 1 (July 2003): 191–192.
Booth, S. L., L. Martini, J. W. Peterson, et al. ‘‘Dietary
Phylloquinone Depletion and Repletion in Older
Women.’’ Journal of Nutrition 133 (August 2003): 2565–
2569.
Iwamoto, J., T. Takeda, and S. Ichimura. ‘‘Treatment with
Vitamin D3 and/or Vitamin K2 for Postmenopausal
Osteoporosis.’’ Keio Journal of Medicine 52 (September
2003): 147–150.
ORGANIZATIONS

American Academy of Pediatrics (AAP). 141 Northwest
Point Boulevard, Elk Grove Village, IL 60007. (847)
434-4000. <http://www.aap.org>.
American Society for Clinical Nutrition. 9650 Rockville
Pike, Bethesda, MD 20814. (301) 530-7110. <http://
www.faseb.org/ascn>.

Tom Brody, PhD
Rebecca J. Frey, PhD

Vitamin poisoning see Vitamin toxicity

Vitamin tests
Definition
Vitamin tests measure the levels of certain vitamins in an individual’s blood. They are generally used
to aid in the diagnosis of vitamin deficiencies or in
detecting toxic amounts of a vitamin in a patient’s
system.

Purpose
Vitamins are components of food that are needed
for growth, reproduction, and maintaining good
health. The vitamins include vitamin D, vitamin E,
vitamin A, and vitamin K, which are the fat-soluble
vitamins, and folate, vitamin B12, biotin, vitamin B6,
GALE ENCYCLOPEDIA OF MEDICINE

niacin, thiamin, riboflavin, pantothenic acid, and
ascorbic acid, which are the water-soluble vitamins.
Vitamins are required in the diet in only tiny amounts,
in contrast to the energy components of the diet, such
as sugars, starches, and fats. However, not receiving
sufficient quantities of a certain vitamin can be devastating, resulting in vitamin deficiency diseases such as
scurvy, pellagra, or rickets. Conversely, consuming
too much of a certain vitamin can be toxic to a person’s system. Vitamin tests are used to assess the level
of certain vitamins in an individual’s blood so that
doctors can more accurately diagnose vitamin deficiency diseases or vitamin overdoses and devise effective therapy. The vitamins that are most commonly
measured by doctors are folate, vitamin B12, vitamin
K, vitamin D, and vitamin A.

Description
Most of the vitamin tests are conducted by acquiring a sample of blood, and then preparing plasma or
serum from the blood sample. Each vitamin occurs at
extremely small concentrations when compared to
levels of most other molecules in the blood. Blood
contains a great number of chemicals and molecules,
and many of these tend to interfere with the vitamin
tests. For this reason, a procedure that separates the
vitamin from contaminating substances is usually performed immediately prior to conducting the actual
test. Most laboratories use high pressure liquid chromatography (HPLC), also called high performance
liquid chromatography, as this purification step. In
HPLC, the sample is pumped at high pressure through
a tube lined with an absorbent material, to which the
different molecules cling at different rates. Following
separation or purification by HPLC, the vitamin is
detected by a color reaction or fluorescence reaction.
In these reactions, the amount of color or fluorescence
that is formed is proportional to the amount of vitamin in the sample, allowing the analyst to calculate the
amount of vitamin present in the original sample. In
the case of some vitamins, the purified vitamin is
reacted with a special chemical (reagent) prior to
detection.
Levels of some vitamins may be measured indirectly by a biological test that mimics the actual function of the vitamin in the body. Riboflavin status is
often measured by a test in which the rate by which a
certain enzyme converts one molecule into another
indicates how much Vitamin B2 is present in a person’s
blood. Vitamin K is often measured by a test that
times how long it takes for a spontaneous blood clot
to form in a prepared sample. Vitamin E status is often
measured by placing the red blood cells in a test tube,
3933

Vitamin tests

sources. Elderly people, especially those living alone,
should be checked for adequate intake of the vitamin.

Vitamin toxicity

adding hydrogen peroxide, and assessing the resulting
breakdown of the red blood cells. When a vitamin E
deficiency exists, the red blood cells have a greater
tendency to break.

Resources
BOOKS

Brody, Tom. Nutritional Biochemistry. San Diego:
Academic Press, 1998.

Tom Brody, PhD

Preparation
Most vitamin tests require no preparation; however, some may require that the patient fast for at least
eight hours before giving a blood sample, or stop using
some medications.

Vitamin toxicity
Normal results
The values that are considered to be normal for
each vitamin can vary slightly. This variability can
arise from different testing machines or from different
types of chemistry that are used in conducting the
vitamin assays. In interpreting data on plasma vitamin
levels, it should also be noted that different normal
ranges may exist for different age groups and genders.
For example, the normal range for plasma vitamin B6
for males is 7-52 nanograms per milliliter (ng/mL) for
males and 2-26 ng/mL for females.
The normal ranges for levels of certain vitamins
are as follows. Please note that, by convention, the
units referring to the levels of each of the vitamins
may differ from each other. The units picogram/milliliter (pg/mL), nanogram/milliliter (ng/mL), and
micrograms per deciliter (micrograms/dL) refer to
the weight of vitamin in the specified volume. The
units nanomoles/liter (nmol/L) and micromoles/liter
(M/L) refer to the concentration of vitamin in the
specified volume.


folate (folic acid): 3.1-18.0 ng/mL



vitamin B12: 200-1100 pg/mL



thiamin: 9-44 nmol/L



riboflavin: 6.2-39 nmol/L



vitamin B6: 7-52 ng/mL



vitamin C (asorbic acid): 28-84 M/L



vitamin A: 28-94 micrograms/dL



vitamin D (25-hydroxy-vitamin D): 25-50 ng/mL



vitamin K: 80-1160 pg/mL

Abnormal results
In all cases, abnormal results fall below or above
the normal concentration range. However, as noted
above, values that are considered to be borderline or
severely abnormal can differ according to the discretion of the medical laboratory or physician.
3934

Definition
Vitamin toxicity is a condition in which a person
develops symptoms as side effects from taking massive
doses of vitamins. Vitamins vary in the amounts that
are required to cause toxicity and in the specific symptoms that result. Vitamin toxicity, which is also called
hypervitaminosis or vitamin poisoning, is becoming
more common in developed countries because of the
popularity of vitamin supplements. Many people treat
themselves for minor illnesses with large doses (megadoses) of vitamins.

Description
Overview
Vitamins are organic molecules in food that are
needed in small amounts for growth, reproduction, and
the maintenance of good health. Some vitamins can be
dissolved in oil or melted fat. These fat-soluble vitamins include vitamin D, vitamin E, vitamin A (retinol),
and vitamin K. Other vitamins can be dissolved in
water. These water-soluble vitamins include folate
(folic acid), vitamin B12, biotin, vitamin B6, niacin,
thiamin, riboflavin, pantothenic acid, and vitamin C
(ascorbic acid). Taking too much of any vitamin can
produce a toxic effect. Vitamin A and vitamin D are the
most likely to produce hypervitaminosis in large doses,
while riboflavin, pantothenic acid, biotin, and vitamin
C appear to be the least likely to cause problems.
Vitamins in medical treatment
Vitamin supplements are used for the treatment
of various diseases or for reducing the risk of certain
diseases. For example, moderate supplements of folic
acid appear to reduce the risk for certain birth defects
(neural tube defects), and possibly reduce the risk
of cancer. Therapy for diseases brings with it the risk
for irreversible vitamin toxicity only in the case of
vitamin D. This vitamin is toxic at levels which are
only moderately greater than the recommended
GALE ENCYCLOPEDIA OF MEDICINE

Vitamin megadoses
With the exception of folic acid supplements, the
practice of taking vitamin supplements by healthy
individuals has little or no relation to good health.
Most adults in the United States can obtain enough
vitamins by eating a well-balanced diet. It has, however, become increasingly common for people to take
vitamins at levels far greater than the RDA. These
high levels are sometimes called vitamin megadoses.
Megadoses are harmless for most vitamins. But in the
cases of a few of the vitamins—specifically vitamin D,
vitamin A, and vitamin B6—megadoses can be harmful or fatal. Researchers have also started to look more
closely at megadoses of vitamin C and of vitamin E,
since indirect evidence suggests that these two vitamins may reduce the risks of cancer, heart disease,
and aging. It is not yet clear whether megadoses of
either of these vitamins has any influence on health.
Some experts think that megadoses of vitamin C may
protect people from cancer. On the other hand, other
researchers have gathered indirect evidence that vitamin C megadoses may cause cancer.

Causes and symptoms
Fat-soluble vitamins
VITAMIN D. Vitamin D and vitamin A are the

most toxic of the fat-soluble vitamins. The symptoms
of vitamin D toxicity are nausea, vomiting, pain in the
joints, and loss of appetite. The patient may experience
constipation alternating with diarrhea, or have tingling
sensations in the mouth. The toxic dose of vitamin D
depends on its frequency. In infants, a single dose of 15
mg or greater may be toxic, but it is also the case that
daily doses of 1.0 mg over a prolonged period may be
toxic. In adults, a daily dose of 1.0-2.0 mg of vitamin D
is toxic when consumed for a prolonged period. A
single dose of about 50 mg or greater is toxic for
adults. The immediate effect of an overdose of vitamin
D is abdominal cramps, nausea and vomiting. Toxic
doses of vitamin D taken over a prolonged period of
time result in irreversible deposits of calcium crystals
in the soft tissues of the body that may damage the
heart, lungs, and kidneys.
VITAMIN A. Vitamin A toxicity can occur with

long-term consumption of 20 mg of retinol or more
GALE ENCYCLOPEDIA OF MEDICINE

per day. The symptoms of vitamin A overdosing
include accumulation of water in the brain (hydrocephalus), vomiting, tiredness, constipation, bone pain,
and severe headaches. The skin may acquire a rough
and dry appearance, with hair loss and brittle nails.
Vitamin A toxicity is a special issue during pregnancy.
Expectant mothers who take 10 mg vitamin A or more
on a daily basis may have an infant with birth defects.
These birth defects include abnormalities of the face,
nervous system, heart, and thymus gland. It is possible
to take in toxic levels of vitamin A by eating large
quantities of certain foods. For example, about 30
grams of beef liver, 500 grams of eggs, or 2,500
grams of mackerel would supply 10 mg of retinol.
The livers of polar bears and other arctic animals
may contain especially high levels of vitamin A.
VITAMIN E. Megadoses of vitamin E may produce
headaches, tiredness, double vision, and diarrhea in
humans. Studies with animals fed large doses of vitamin E have revealed that this vitamin may interfere
with the absorption of other fat-soluble vitamins. The
term absorption means the transfer of the vitamin
from the gut into the bloodstream. Thus, large doses
of vitamin E consumed over many weeks or months
might result in deficiencies of vitamin D, vitamin A,
and vitamin K.
VITAMIN K. Prolonged consumption of megadoses
of vitamin K (menadione) results in anemia, which is a
reduced level of red blood cells in the bloodstream.
When large doses of menadione are given to infants,
they result in the deposit of pigments in the brain, nerve
damage, the destruction of red blood cells (hemolysis),
and death. A daily injection of 10 mg of menadione into
an infant for three days can kill the child. This tragic
fact was discovered during the early days of vitamin
research, when newborn infants were injected with
menadione to prevent a disease known as hemorrhagic
disease of the newborn. Today a different form of
vitamin K is used to protect infants against this disease.

Water-soluble vitamins
FOLATE. Folate occurs in various forms in food.
There are over a dozen related forms of folate. The
folate in oral vitamin supplements occurs in only one
form, however—folic acid. Large doses of folic acid
(20 grams/day) can result in eventual kidney damage.
Folate is considered, however, to be relatively nontoxic, except in cases where folate supplementation
can lead to pernicious anemia.
VITAMIN B12. Vitamin B12 is important in the
treatment of pernicious anemia. Pernicious anemia is
more common among middle-aged and older adults; it

3935

Vitamin toxicity

dietary allowance (RDA). Niacin is commonly used as
a drug for the treatment of heart disease. Niacin is far
less toxic than vitamin D. Vitamin toxicity is not a risk
with medically supervised therapy using any of the
other vitamins.

Vitamin toxicity

is usually detected in patients between the ages of 40
and 80. The disease affects about 0.1% of all persons
in the general population in the United States, and
about 3% of the elderly population. Pernicious anemia is treated with large doses of vitamin B12.
Typically, 0.1 mg of the vitamin is injected each week
until the symptoms of pernicious anemia disappear.
The patient then takes oral doses of vitamin B12 for the
rest of his or her life. Although vitamin B12 toxicity is
not an issue for patients being treated for pernicious
anemia, treatment of these patients with folic acid may
cause problems. Specifically, pernicious anemia is
often first detected because the patient feels weak or
tired. If the anemia is not treated, the patient may
suffer irreversible nerve damage. The problem with
folic acid supplements is that the folic acid treatment
prevents the anemia from developing, but allows the
eventual nerve damage to occur.
VITAMIN B6. Vitamin B6 is clearly toxic at doses
about 1000 times the RDA. Daily doses of 2-5 grams of
one specific form of this vitamin can produce difficulty
in walking and tingling sensations in the legs and soles
of the feet. Continued megadoses of vitamin B6 result
in further unsteadiness, difficulty in handling small
objects, and numbness in the hands. When the high
doses are stopped, recovery begins after two months.
Complete recovery may take two to three years.
VITAMIN C. The RDA for vitamin C in adults is 60
mg per day. Large doses of vitamin C are considered to
be toxic in persons with a family history of or tendency
to form kidney stones or gallbladder stones. Kidney
and gallbladder stones usually consist of calcium oxalate. Oxalate occurs in high concentrations in foods
such as cocoa, chocolate, rhubarb, and spinach. A
fraction of the vitamin C in the body is normally
broken down in the body to produce oxalate. A daily
supplement of 3.0 grams of vitamin C has been found
to double the level of oxalate that passes through the
kidneys and is excreted into the urine.
NIACIN. The RDA for niacin is 15-19 mg per day
in adults. Niacin comes in two forms, nicotinic acid
and nicotinamide. Either form can satisfy the adult
requirement for this vitamin. Nicotinic acid, however,
is toxic at levels of 100 times the RDA. It can cause
flushing of the skin, nausea, diarrhea, and liver
damage. Flushing is an increase in blood passing
through the veins in the skin, due to the dilation of
arteries passing through deeper parts of the face or
other parts of the body. In spite of the side effects,
however, large doses of nicotinic acid are often used to
lower blood cholesterol in order to prevent heart
disease. Nicotinic acid results in a lowering of LDLcholesterol (‘‘bad cholesterol’’), an increase in HDL-

3936

cholesterol (‘‘good cholesterol’’), and a decrease in
plasma triglycerides. Treatment involves daily doses
of 1.5-4.0 grams of nicotinic acid per day. Flushing of
the skin occurs as a side effect when nicotinic acid
therapy is started, but may disappear with continued
therapy.

Diagnosis
The diagnosis of vitamin toxicity is usually made
on the basis of the patient’s dietary or medical history.
Questioning the patient about the use of vitamin supplements may shed light on some of his or her physical
symptoms. With some vitamins, the doctor can confirm the diagnosis by ordering blood or urine tests for
specific vitamins. When large amounts of the watersoluble vitamins are consumed, a large fraction of the
vitamin is absorbed into the bloodstream and
promptly excreted into the urine. The fat-soluble vitamins are more likely to be absorbed into the bloodstream and deposited in the fat and other tissues. In
the cases of both water-soluble and fat-soluble vitamins, any vitamin not absorbed by the intestines is
excreted in the feces. Megadoses of many of the vitamins produce diarrhea, because the non-absorbed
nutrient draws water out of the body and into the
gut, resulting in the loss of this water from the body.

Treatment
In all cases, treatment of vitamin toxicity requires
discontinuing vitamin supplements. Vitamin D toxicity needs additional action to reduce the calcium
levels in the bloodstream because it can cause abnormally high levels of plasma calcium (hypercalcemia).
Severe hypercalcemia is a medical emergency and may
be treated by infusing a solution of 0.9% sodium
chloride into the patient’s bloodstream. The infusion
consists of two to three liters of salt water given over a
period of one to two days.

Prognosis
The prognosis for reversing vitamin toxicity is
excellent for most patients. Side effects usually go
away as soon as overdoses are stopped. The exceptions
are severe vitamin D toxicity, severe vitamin A toxicity, and severe vitamin B6 toxicity. Too much vitamin
D leads to deposits of calcium salts in the soft tissue of
the body, which cannot be reversed. Birth defects due
to vitamin A toxicity cannot be reversed. Damage to
the nervous system caused by megadoses of vitamin
B6 can be reversed, but complete reversal may require
a recovery period of over a year.
GALE ENCYCLOPEDIA OF MEDICINE

Absorption—The transfer of a vitamin from the
digestive tract to the bloodstream.
Ascorbic acid—Another name for vitamin C.
Hypercalcemia—Hypercalcemia is a condition
marked by abnormally high levels of calcium in
the blood. It is an issue during vitamin D toxicity.
Hypervitaminosis—Another name for vitamin
toxicity.
Megadose—A very large dose of a vitamin, taken
by some people as a form of self-medication.
Menadione—A synthetic form of vitamin K. It is
sometimes called vitamin K3.
Recommended Dietary Allowance (RDA)—The
recommended dietary allowances (RDAs) are the
quantities of nutrients in the diet that are needed for
good health. RDAs are established by the Food and
Nutrition Board of the National Academy of
Sciences and may be revised every few years.
Retinol—Another name for vitamin A.

Prevention
Vitamin toxicity can be prevented by minimizing
the use of vitamin supplements. If vitamin D supplements are being used on a doctor’s orders, vitamin
toxicity can be prevented by monitoring the levels of
plasma calcium. The development of hypercalcemia
with vitamin D treatment indicates that the patient is
at risk for vitamin D toxicity.
Resources
BOOKS

Brody, Tom. Nutritional Biochemistry. San Diego:
Academic Press, 1998.

Tom Brody, PhD

Vitamins

fat-soluble vitamins, and folate (folic acid), vitamin
B12, biotin, vitamin B6, niacin, thiamin, riboflavin,
pantothenic acid, and vitamin C (ascorbic acid), or
the water-soluble vitamins. Vitamins are required in
the diet in only tiny amounts, in contrast to the energy
components of the diet. The energy components of the
diet are sugars, starches, fats, and oils, and these occur
in relatively large amounts in the diet.
Most of the vitamins are closely associated with a
corresponding vitamin deficiency disease. Vitamin D
deficiency leads to diseases of the bones such as osteoporosis and rickets. Vitamin E deficiency occurs only
rarely, and causes nerve damage. Vitamin A deficiency
is common throughout the poorer parts of the world,
and causes night blindness. Severe vitamin A deficiency can result in xerophthalamia, a disease which,
if left untreated, results in total blindness. Vitamin K
deficiency results in spontaneous bleeding. Mild or
moderate folate deficiency is common throughout
the world, and can result from the failure to eat
green, leafy vegetables or fruits and fruit juices.
Folate deficiency causes megaloblastic anemia, which
is characterized by the presence of large abnormal cells
called megaloblasts in the circulating blood. The
symptoms of megaloblastic anemia are tiredness and
weakness. Vitamin B12 deficiency occurs with the failure to consume meat, milk or other dairy products.
Vitamin B12 deficiency causes megaloblastic anemia
and, if severe enough, can result in irreversible nerve
damage. Niacin deficiency results in pellagra. Pellagra
involves skin rashes and scabs, diarrhea, and mental
depression. Thiamin deficiency results in beriberi, a
disease that can cause atrophy, weakness of the legs,
nerve damage, and heart failure. Vitamin C deficiency
results in scurvy, a disease that involves bleeding.
Specific diseases uniquely associated with deficiencies
in vitamin B6, riboflavin, or pantothenic acid have not
been found in humans, though persons who have been
starving, or consuming poor diets for several months,
might be expected to be deficient in most of the nutrients, including vitamin B6, riboflavin, and pantothenic
acid.
Some of the vitamins serve only one function in
the body, while other vitamins serve a variety of unrelated functions. Therefore, some vitamin deficiencies
tend to result in one type of defect, while other deficiencies result in a variety of problems.

Definition
Vitamins are organic components in food that are
needed in very small amounts for growth and for
maintaining good health. The vitamins include vitamin D, vitamin E, vitamin A, and vitamin K, or the
GALE ENCYCLOPEDIA OF MEDICINE

Purpose
People are treated with vitamins for three reasons. The primary reason is to relieve a vitamin deficiency, when one has been detected. Chemical tests
3937

Vitamins

KEY TERMS

Vitamins

Essential Vitamins

Vitamin

What It Does For The Body

Vitamin A (Beta
Carotene)

Promotes growth and repair of body tissues; reduces
susceptibility to infections; aids in bone and teeth
formation; maintains smooth skin
Promotes growth and muscle tone; aids in the proper
functioning of the muscles, heart, and nervous system; assists in digestion of carbohydrates
Maintains good vision and healthy skin, hair, and
nails; assists in formation of antibodies and red blood
cells; aids in carbohydrate, fat, and protein
metabolism
Reduces cholesterol levels in the blood; maintains
healthy skin, tongue, and digestive system; improves
blood circulation; increases energy
Fortifies white blood cells; helps the body’s resistance to stress; builds cells
Aids in the synthesis and breakdown of amino acids
and the metabolism of fats and carbohydrates; supports the central nervous system; maintains healthy
skin
Promotes growth in children; prevents anemia by
regenerating red blood cells; aids in the metabolism
of carbohydrates, fats, and proteins; maintains
healthy nervous system
Aids in the metabolism of proteins and fats; promotes
healthy skin
Helps the liver eliminate toxins
Promotes the growth and reproduction of body cells;
aids in the formation of red blood cells and bone
marrow
One of the major antioxidants; essential for healthy
teeth, gums, and bones; helps to heal wounds, fractures, and scar tissue; builds resistance to infections;
assists in the prevention and treatment of the common cold; prevents scurvy
Improves the absorption of calcium and phosphorous (essential in the formation of healthy bones and
teeth) maintains nervous system
A major antioxidant; supplies oxygen to blood; provides nourishment to cells; prevents blood clots;
slows cellular aging
Prevents internal bleeding; reduces heavy menstrual
flow

Vitamin B-1
(Thiamin)
Vitamin B-2
(Riboflavin)

Vitamin B-3
(Niacinamide)
Vitamin B-5
Vitamin B-6
(Pyridoxine)

Vitamin B-12
(Cobalamin)

Biotin
Choline
Folic Acid
(Folate, Folacin)
Vitamin C
(Ascorbic Acid)

Vitamin D

Vitamin E

Vitamin K
(Menadione)

suitable for the detection of all vitamin deficiencies
are available. The diagnosis of vitamin deficiency
often is aided by visual tests, such as the examination
of blood cells with a microscope, the x-ray examination of bones, or a visual examination of the eyes or
skin.
A second reason for vitamin treatment is to prevent the development of an expected deficiency. Here,
vitamins are administered even with no test for possible deficiency. One example is vitamin K treatment of
newborn infants to prevent bleeding. Food supplementation is another form of vitamin treatment. The
vitamin D added to foods serves the purpose of preventing the deficiency from occurring in persons who
may not be exposed much to sunlight and who fail to
3938

consume foods that are fortified with vitamin D, such
as milk. Niacin supplementation prevents pellagra, a
disease that occurs in people who rely heavily on corn
as the main source of food, and who do not eat much
meat or milk. In general, the American food supply is
fortified with niacin.
A third reason for vitamin treatment is to reduce
the risk for diseases that may occur even when vitamin deficiency cannot be detected by chemical tests.
One example is folate deficiency. The risk for cardiovascular disease can be slightly reduced for a large
fraction of the population by folic acid supplements.
And the risk for certain birth defects can be sharply
reduced if certain pregnant women use folic acid
supplements.
Vitamin treatment is important during specific
diseases where the body’s normal processing of a
vitamin is impaired. In these cases, high doses of the
needed vitamin can force the body to process or
utilize it in the normal manner. One example is pernicious anemia, a disease that tends to occur in middle age or old age, and impairs the absorption of
vitamin B12. Surveys have revealed that about 0.1%
of the general population, and 2–3% of the elderly,
may have the disease. If left untreated, pernicous
anemia leads to nervous system damage. The disease
can easily be treated with large oral daily doses of
vitamin B12 (hydroxocobalamin) or with monthly
injections of the vitamin.
Vitamin supplements are widely available as
over-the-counter products. But whether they work
to prevent or curtail certain illnesses, particularly in
people with a balanced diet, is a matter of debate and
ongoing research. For example, vitamin C is not
proven to prevent the common cold. Yet, millions of
people take it for that reason. A physician or pharmacist can provide more information on the appropriate use of multivitamin supplements. Likewise,
though vitamin supplements have been touted as a
prevention for cancer, a 2004 report by the U.S.
Preventive Services Task Force concluded that the
evidence is inadequate to recommend supplementation of vitamins A, C, or E, multivitamins with folic
acid, or antioxidant combinations to decrease the
risk of cancer.

Precautions
Vitamin A and vitamin D can be toxic in high
doses. Side effects range from dizziness to kidney failure. A physician or pharmacist can help with the correct use of a multivitamin supplement that contains
these vitamins.
GALE ENCYCLOPEDIA OF MEDICINE

Genetic disease—A genetic disease is a disease
that is passed from one generation to the next,
but does not necessarily appear in each generation. An example of genetic disease is Down’s
syndrome.
Plasma—Blood consists of red and white cells, as
well as other components, that float in a liquid. This
liquid is called plasma.
Recommended dietary allowance (RDA)—The
Recommended Dietary Allowances (RDAs) are
quantities of nutrients of the diet that are required
to maintain human health. RDAs are established by
the Food and Nutrition Board of the National
Academy of Sciences and may be revised every
few years. A separate RDA value exists for each
nutrient. The RDA values refer to the amount of
nutrient expected to maintain health in the greatest
number of people.
Serum—Serum is blood plasma with the blood
clotting proteins removed. Serum is prepared by
removing blood from the subject, allowing the
blood naturally to form a blood clot, and then
using a centrifuge to remove the red blood cells
and the blood clot. The blood clot takes the form
of an indistinct clump.
Vitamin status—Vitamin status refers to the state
of vitamin sufficiency or deficiency of any person.
For example, a test may reveal that a patient’s
folate status is sufficient, borderline, or severely
inadequate.

Description
Vitamin treatment usually is done in three ways:
by replacing a poor diet with one that supplies the
recommended dietary allowance, by consuming oral
supplements, or by injections. Injections are useful
for people with diseases that prevent absorption of
fat-soluble vitamins. Oral vitamin supplements are
especially useful for people who otherwise cannot or
will not consume food that is a good vitamin source,
such as meat, milk, or other dairy products. For
example, a vegetarian who will not consume meat
may be encouraged to consume oral supplements of
vitamin B12.
Treatment of genetic diseases that impair the
absorption or utilization of specific vitamins may
GALE ENCYCLOPEDIA OF MEDICINE

require megadoses of the vitamin throughout one’s
lifetime. Megadose means a level of about 10-1,000
times greater than the recommended daily allowance (RDA). Pernicious anemia, homocystinuria,
and biotinidase deficiency are three examples of
genetic diseases that are treated with megadoses
of vitamins.

Preparation
The diagnosis of a vitamin deficiency usually
involves a blood test. An overnight fast usually is
recommended as preparation prior to withdrawal of
the blood test so that vitamin-fortified foods do not
affect the test results.

Aftercare
Response to vitamin treatment can be monitored
by chemical tests, by an examination of red blood cells
or white blood cells, or by physiological tests, depending on the exact vitamin deficiency.

Risks
Few risks are associated with supervised vitamin
treatment. Risks depend on the vitamin and the reason
why it was prescribed. Ask a physician or pharmacist
about how and when to take vitamin supplements,
particularly those that have not been prescribed by a
physician.
Resources
PERIODICALS

‘‘The Next Big Deficiency.’’ Chain Drug Review February
16, 2004: 26.
Sadovsky, Richard. ‘‘Can Vitamins Prevent Cancer and
Heart Disease?’’ American Family Physician February
1, 2004: 631.

Tom Brody, PhD
Teresa G. Odle

Vitiligo
Definition
Vitiligo is a condition in which a loss of cells that
give color to the skin (melanocytes) results in smooth,
white patches in the midst of normally pigmented
skin.
3939

Vitiligo

KEY TERMS

Vitiligo

KEY TERMS
Autoimmune disease—A condition in which something triggers the immune system to react against
and attack the body’s own tissues.
Autologous
transplantation—A
procedure
wherein the person donates blood or tissue to
themselves.
Iris—The colored part of the eye.
Pernicious anemia—A disease in which red blood
cells are abnormally formed due to the body’s
inability to absorb vitamin B12.
Loss of pigmentation is one characteristic of vitiligo, as seen
on this woman’s hand. (Custom Medical Stock Photo.
Reproduced by permission.)

Retina—The innermost layer of the eye, it contains
the rods and cones, specialized light-sensitive
cells.

Description
Vitiligo is a common, often inherited disorder
characterized by areas of well-defined, milky white
skin. People with vitiligo may have eye abnormalities
and also have a higher incidence of thyroid disease,
diabetes mellitus, and pernicious anemia. Vitiligo
affects about 1-2% of the world’s population. It is
more easily observed in sun-exposed areas of the
body and in darker skin types, but it affects any area
of the body and all races. Vitiligo seems to affect men
and women equally, although women more frequently
seek treatment for the disorder.
Vitiligo may appear as one or two well-defined
white patches or it may appear over large portions of
the body. Typical sites for generalized vitiligo are areas
surrounding body openings, bony areas, fingers, and
toes. It can begin at any age but about 50% of the time
it starts before the age of 20.

Causes and symptoms
Vitiligo is a disorder with complex causes. People
with vitiligo seem to inherit a genetic predisposition
for the disorder, and the appearance of disorder can be
brought on by a variety of precipitating causes. Many
people report that their vitiligo first appeared following a traumatic or stressful event, such as an accident,
job loss, death of a family member, severe sunburn, or
serious illness. There are at least three theories about
the underlying mechanism of vitiligo. One theory says
nerve endings in the skin release a chemical that is
toxic to the melanocytes. A second theory states that
the melanocytes simply self-destruct. The third explanation is that vitiligo is a type of autoimmune disease
3940

in which the immune system targets the body’s own
cells and tissues.
The primary symptom of vitiligo is the loss of
skin color. Hair growing from the affected skin areas
also lacks color. In addition, people with vitiligo may
have pigment abnormalities of the retina or iris of the
eyes. A minority of patients also may have inflammation of the retina or iris, but vision is not usually
impaired.

Diagnosis
The diagnosis of vitiligo is usually made by observation. Progressive, white areas found at typical sites
point to a diagnosis of vitiligo. If the diagnosis is not
certain, the doctor will test for other conditions which
can mimic vitiligo, such as chemical leukoderma or
systemic lupus erythematosus. If the tests rule out other
conditions, vitiligo is confirmed.

Treatment
Vitiligo cannot be cured, but it can be managed.
Cosmetics can be used to improve the appearance of
the white areas not covered by clothing. Sunscreens
prevent burning of the affected areas and also prevent
the normal skin around the patches from becoming
darker. Skin creams and oral medications are available for severe cases, but they have side effects that
may make them undesirable. Autologous transplantation of skin is an option for those who are severely
affected. Bleaching or depigmentation of the normal
skin is another option.
GALE ENCYCLOPEDIA OF MEDICINE

Vitrectomy

In addition to treating the skin, attention should
be paid to the psychological well-being of the individual. Extreme cases of vitiligo can be unattractive and
may affect a person’s outlook and social interactions.

Prognosis
The condition is usually gradually progressive.
Sometimes the patches grow rapidly over a short period, and then the condition remains stable for many
years.

Prevention
No measures are currently known to prevent
vitiligo.
Resources
ORGANIZATIONS

Frontier’s International Vitiligo Foundation. 4 Rozina
Court, Owings Mills, MD 21117. (301) 594-0958.
National Foundation for Vitiligo and Pigment Disorders.
9032 South Normandy Drive, Centerville, OH 45459.
(513) 885-5739.
National Vitiligo Foundation. P.O. Box 6337, Tyler, TX
75703. (903) 531-9767.
<73071.33@compuserve.com>.

Dorothy Elinor Stonely

Vitrectomy is a surgical procedure in which the vitreous, the
transparent gel that fills the eye from the iris to the retina, is
removed. During this procedure, the surgeon penetrates the
eyeball with a tiny instrument (shown above), which liquefies
the vitreous and suctions it out of the eye. (Photo Researchers,
Inc. Reproduced by permission.)

The retina is the light-sensitive membrane that
receives images and transmits them to the brain. It
covers the inside of the back of the eye. On occasion the retina will fall into the vitreous, a condition called retinal detachment. This may be due to
disease in the vitreous that pulls the retina inward,
small tears in the retina that allow liquid to seep
behind it and push it forward, or injury to the eye
that simply breaks the retina loose. It may be
necessary to remove the vitreous in order to replace
the retina and restore vision.

Description

Vitrectomy
Definition
Vitrectomy is the surgical removal of the vitreous
(transparent gel that fills the eye from the iris to the
retina).

Purpose
The bulk of the contents of the eyeball is a clear
jelly-like substance that is susceptible to several
afflictions that impair vision by damaging its
transparency.


Infections



Injuries



Bleeding, particularly from diabetic retinopathy



Blood vessels growing into the vitreous, again due to
diabetes.

GALE ENCYCLOPEDIA OF MEDICINE

Using instruments suited for microscopic surgery,
the ophthalmologist (eye surgeon) penetrates the eyeball, aspirates the vitreous, and replaces it with saline.
The saline replaces the vitreous at a constant pressure
in order to keep the eye from collapsing. Once the
saline is in place, both eyes are patched. The procedure
takes two to three hours to complete.

Preparation
Because this is a major operation on the eye, the
surgeon will perform a very extensive evaluation of both
eyes. After looking inside with a variety of lenses, a CT,
MRI, or ultrasound study may be needed. Immediately
prior to the vitrectomy, the pupils will be dilated.

Aftercare
Eye drops and antibiotics are administered, and
eye rest is advised until healing is completed.
3941

Vocal cord nodules and polyps

Description

KEY TERMS
Computed tomography (CT scan)—Computerized
method of creating images of internal organs using
x rays.
Diabetic retinopathy—Disease that damages the
blood vessels in the back of the eye caused by
diabetes mellitus.
Endophthalmitis—Inflammation of the eyeball.
Iatrogenic—Inadvertently caused by medical
treatment.
Magnetic resonance imaging (MRI)—Computer
ized method of creating images of internal organs
using magnetic fields.
Saline—A salt solution equivalent to that in the
body—0.9% salt in water.

Risks
Risks associated with vitrectomy are retinal
detachment, bleeding, iatrogenic (medically caused)
cataracts, and endophthalmitis (inflammation of the
eyeball).

Normal results

The vocal cords, located in the voice box in the
middle of the neck, are two tough, fibrous bands that
vibrate to produce sound. They are covered with a
layer of tissue that is similar to skin. With use, this
layer thickens. With heavy use, the thickening may
localize, producing a nodule. Unlike skin, heavy
usage over a short time may also produce polyps. A
polyp is a soft, smooth lump containing mostly blood
and blood vessels. A nodule is similar to a polyp, but
tends to be firmer.

Causes and symptoms
Chronic infections caused by allergies and inhalation of irritants, such as cigarette smoke, may produce
these lesions, but extensive use of the voice is the most
common cause of vocal nodules and polyps. Nodules
and polyps are more common in male children, female
adolescents, and female adults. This may be due in
part to the faster speed at which the cords vibrate to
produce higher-pitched voices.
Voice alterations are most apparent in singers,
who may notice the higher registers are the first to
change. Hoarseness causes others to seek medical
attention.

Diagnosis

Vision is restored to useful levels in two-thirds of
patients.
Resources
BOOKS

O’Malley, Conor. ‘‘Vitreous.’’ In General Ophthalmology,
edited by Daniel Vaughan, 13th ed. Stamford:
Appleton & Lange, 1993.

J. Ricker Polsdorfer, MD

Vivax malaria see Malaria

The head and neck surgeon (otorhinolaryngologist) must see the vocal cords to diagnose these lesions.
It is also important to confirm that there are not other
problems instead of or in addition to these benign
lumps. Other causes of hoarseness include throat cancers, vocal cord paralysis, and simple laryngitis. The
cords can usually be seen using a mirror placed at the
back of the tongue. More elaborate scopes, including a
videostroboscope, allow better views while the cords
are producing sounds.
A biopsy of a nodule or polyp will ensure they are
not cancerous.

Treatment

Vocal cord nodules and polyps

Nodules usually only require voice therapy; less
than 5% of nodules require surgery. Small polyps can
be treated with voice therapy, but typically they are
surgically removed.

Definition
Vocal cord nodules and polyps are noncancerous growths on the vocal cords that affect the
voice.
3942

Prognosis
Continued overuse of the voice will cause these
lesions to regrow.
GALE ENCYCLOPEDIA OF MEDICINE

cords can either be partially paralyzed on one side or
completely paralyzed on both sides.

Laryngitis—Inflammation of the larynx (voice box).
Lesion—A wound or injury.
Otorhinolaryngologist—A physician specializing
in ear, nose, and throat diseases. Also known as
otolaryngologist.

Prevention
Careful use of the voice will prevent most vocal
cord nodules and polyps. Avoiding inhaled irritants,
may also prevent nodules and polyps from forming.

Causes and symptoms
Vocal cord paralysis can result from injury,
tumors, or surgery in the neck and upper chest. Brain
tumors and stroke can also affect the nerves.
Infectious diseases that damage nerves—like whooping
cough, tetanus and polio—can also cause vocal cord
paralysis. Vocal cord paralysis can also appear as a
congenital defect. If congenital, the most frequent
cause is a brain defect, which can often be effectively
treated.

Ballenger, John Jacob. Disorders of the Nose, Throat, Ear,
Head, and Neck. Philadelphia: Lea & Febiger, 1991.

The most dangerous form of vocal cord paralysis
is one that affects the opening function, controlled by
the recurrent laryngeal nerve. If both vocal cords are
paralyzed, breathing stops or becomes very labored.
Fortunately, injury during trauma or surgery often
involves only one side, but the congenital causes can
damage both sides.

J. Ricker Polsdorfer, MD

Vocal cord paralysis produces several symptoms.

Resources
BOOKS



The voice is always affected; at best it is breathy and
weak. At worst, it is not there at all. In infants, the cry
can be weak. Older children will suppress laughing
and coughing because it is hard to do.



Swallowing may be hindered so that food ends up in
the airway, causing violent coughing and often leading to pneumonia.



Breathing is obstructed on inspiration, producing a
condition known as stridor. Closing the airway while
breathing in produces creaking noises in the throat
and changes the shape of the chest. The breast bone is
drawn inward, much more visibly in the flexible chest
of a small child.

Vocal cord paralysis
Definition
Vocal cord paralysis is the inability to move the
vocal cords and the resulting loss of vocal cord
function.

Description
The vocal cords are a pair of tough, fibrous bands
that lie across the air column in the middle of the voice
box. They assist three functions: breathing, swallowing, and speaking. When vocal cords vibrate, they
produce sound, allowing us to speak. Vocal cords
temporarily stop breathing to aid coughing and for
expelling foreign objects. During swallowing, the vocal
cords shut the airway so that food is not inhaled.
When vocal cords are paralyzed, all three functions
are affected.
The relaxed position of the vocal cords is halfway
open. There is one set of muscles that closes them all
the way and one set that opens them. Each set of
muscles is controlled by a different nerve. Each nerve
comes from a different direction—one from above and
one from below (the recurrent laryngeal nerve). Vocal
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
The voice box must be observed during breathing
to characterize the problem. A viewing instrument
called a laryngoscope, either flexible or rigid, is passed
through the nose or throat until the cords becomes
visible. The motion of each cord can then be seen, and
other problems in the area identified.
X rays, CT, or MRI scans of the skull may be done
if a brain disorder is suspected.

Treatment
An adequate airway is immediately necessary,
usually secured with an endotracheal tube in the windpipe. If a cure cannot be achieved, a permanent
3943

Vocal cord paralysis

KEY TERMS

Von Willebrand disease

KEY TERMS
Computed tomography (CT scan)—Computerized
use of x rays to create images of internal organs.
Laryngoscope—A diagnostic instrument that is
used to examine the interior of the larynx.
Magnetic
resonance
imaging
(MRI)—
Computerized use of magnetic fields and radiofrequency signals to create images of internal
organs.
Recurrent laryngeal nerve—One of two offshoots
of the vagus nerve that connect to the larynx. It is
located below the larynx.
Stridor—A raspy sound that occurs during respiration when the airways are blocked.
Tracheostomy—Surgical opening in the neck to the
trachea to aid respiration.
Voice box—The larynx.

Vomiting see Nausea and vomiting; Cyclic
vomiting syndrome; Hyperemesis
gravidarum
Von Gierke’s disease see Glycogen storage
diseases
Von Recklinghausen disease see
Neurofibromatosis

Von Willebrand disease
Definition
Von Willebrand disease is caused by a deficiency
or an abnormality in a protein called von Willebrand
factor and is characterized by prolonged bleeding.

Description
breathing hole (tracheostomy) is cut in the neck. Brain
problems that are relieved within 24 hours usually
allow the cords to regain their function. Care must
be taken to assure that swallowing takes place
normally.

Alternative treatment
Vocal cord paralysis can be addressed with constitutional homeopathy. This will work with the whole
person, not just the symptoms, to help bring about
healing. Botanical medicine and deep tissue massage
to the area can also bring some resolution, although it
may not be long term.
Resources
BOOKS

Ballenger, John Jacob. Disorders of the Nose, Throat, Ear,
Head, and Neck. Philadelphia: Lea & Febiger, 1991.

J. Ricker Polsdorfer, MD

Vocal cord polyps see Vocal cord nodules
and polyps
Voiding cystourethrography see Retrograde
urethrography
Volvulus see Intestinal obstructions
3944

The Finnish physician Erik von Willebrand was
the first to describe von Willebrand disease (VWD). In
1926 Dr. von Willebrand noticed that many male and
female members of a large family from the Aland
Islands had increased bruising (bleeding into the
skin) and prolonged episodes of bleeding. The severity
of the bleeding varied between family members and
ranged from mild to severe and typically involved the
mouth, nose, genital and urinary tracts, and occasionally the intestinal tract. Excessive bleeding during the
menstrual period (menorrhagia) was also experienced
by some of the women in this family. What differentiated this bleeding disorder from classical hemophilia
was that it appeared not to be associated with muscle
and joint bleeding and affected people of either sex
rather than just men. Dr. von Willebrand named this
disorder hereditary pseudohemophilia.
Pseudohemophilia, or von Willebrand disease
(VWD) as it is now called, occurs when the body
does not produce enough of a protein called von
Willebrand factor(vWF) or produces abnormal
vWF. vWF is involved in the process of blood clotting
(coagulation). Blood clotting is necessary to heal an
injury to a blood vessel. When a blood vessel is injured,
vWF enables blood cells called platelets to bind to the
injured area and form a temporary plug to seal the
hole and stop the bleeding. vWF is secreted by platelets and by the cells that line the inner wall of the blood
vessels (endothelial cells). The platelets release other
chemicals called factors in response to a blood vessel
injury that are involved in forming a strong permanent
GALE ENCYCLOPEDIA OF MEDICINE

A deficiency or abnormality in vWF can interfere
with the formation of the temporary platelet plug and
also affect the normal survival of factor VIII, which
can indirectly interfere with the production of the
permanent clot. Individuals with VWD, therefore,
have difficulty in forming blood clots and as a result
they may bleed for longer periods of time. In most
cases the bleeding is due to an obvious injury,
although it can sometimes occur spontaneously.
VWD is classified into three basic types: type 1,
type 2, and type 3. The definitions of each type are
based on the amount and type of vWF that is produced. Type 1 is the most common and mildest form
and results when the body produces slightly decreased
amounts of typically normal vWF. Type 2 can be
classified into four subtypes (IIA,IIB,IIM, and IIN)
and results when the body produces an abnormal type
of vWF. Type 3 is the rarest and most severe form and
results when the body does not produce any detectable
amount of vWF.
Approximately one out of 100 people are affected
with VWD, making it the most common inherited
bleeding disorder (hemophilia). VWD affects people
of all ethnic backgrounds. Approximately 70–80% of
people with VWD have type 1 and close to 20–30%
have type 2. Type 3 is very rare and occurs in fewer
than one percent of people with VWD.

Causes and symptoms
The genetics of VWD are complex and involve a
gene that produces vWF and is found on the short arm
of chromosome 12. Since humans inherit two of each
type of chromosome, they inherit two vWF genes.
There are different types of changes (mutations) in
the vWF gene that can affect the production of vWF.
Some types of changes can cause the vWF gene to
produce decreased amounts of normal vWF, while
other changes can cause the gene to produce abnormal
vWF. Most of the gene changes are significant enough
that a change in only one vWF gene is sufficient to
cause VWD. Some gene mutations cause VWD only if
both genes are changed, which often leads to more
severe symptoms.
Type 1 VWD is called an autosomal dominant
condition since it is caused by a change in only one
vWF gene. Since type 1 VWD results in only a slight
decrease in the amount of vWF produced, the symptoms are often mild and even non-existent in some
patients. Most cases of Type 2 VWD are autosomal
GALE ENCYCLOPEDIA OF MEDICINE

dominant since they are caused by a change in only
one vWF gene that results in the production of an
abnormal protein. An autosomal dominant form of
VWD can be inherited from either parent or can occur
spontaneously in the embryo that is formed when the
egg and sperm cells come together during fertilization.
Some cases of type 2 VWD and all cases of type
3 VWD are autosomal recessive since they are caused
by changes in both vWF genes. A person with an
autosomal recessive form of VWD has inherited a
changed gene from his or her mother and a changed
gene from his or her father. Parents who have a child
with an autosomal recessive form of VWD are called
carriers, since they each possess one changed vWF
gene and one unchanged vWF gene. Many carriers
for the autosomal recessive forms of type 2 VWD
and type 3 VWD do not have any symptoms, although
some people with type 3 VWD are born to parents who
have type 1 VWD and may have symptoms. Each child
born to parents who are both carriers for VWD has a
25% chance of having VWD, a 50% chance of being a
carrier, and a 25% chance of being neither a carrier
nor affected with VWD disease. A person with an
autosomal dominant form of VWD has a 50% chance
of passing the changed gene on to his or her children
who may or may not have symptoms.
VWD is usually a relatively mild disorder characterized by easy bruising, recurrent nosebleeds, heavy
menstrual periods, and extended bleeding after surgeries and invasive dental work. There is a great deal
of variability in the severity of symptoms, which can
range from clinically insignificant to life-threatening.
Even people within the same family who are affected
with the same type of VWD may exhibit different
symptoms. An individual with VWD may exhibit a
range of symptoms over the course of his or her lifetime and may experience an improvement in symptoms with age. The severity of the disease is partially
related to the amount and type of vWF that the body
produces, but is also influenced by other genetic and
non-genetic factors.
Type 1
Type 1, the mildest form of VWD, is usually associated with easy bruising, recurrent nosebleeds, heavy
menstrual periods, and prolonged bleeding after surgeries and invasive work. Many people with type 1
VWD do not have any noticeable symptoms or only
have prolonged bleeding after surgery or significant
trauma. The amount of vWF produced by the body
increases during pregnancy, so prolonged bleeding
during delivery is uncommon in people with type 1
VWD.
3945

Von Willebrand disease

clot. vWF binds to and stabilizes factor VIII, one of
the factors involved in forming the permanent clot.

Von Willebrand disease

Type 2
People with type 2 VWD usually have symptoms
from early childhood and symptoms may even be present at birth. They usually experience prolonged bleeding from cuts, easy bruising, nose bleeds, skin
hematomas, and prolonged bleeding from the gums
following teeth extraction and minor trauma. More
than 50% of women with type 2 VWD experience
heavy periods that may require a blood transfusion.
Gastrointestinal bleeding is rare but can be life-threatening. Some women with type 2 VWD exhibit prolonged bleeding during delivery.
Type 3
Type 3 VWD can be quite severe and is associated
with bruising and bleeding from the mouth, nose,
intestinal, genital and urinary tracts. Type 3 is also
associated with spontaneous bleeding into the muscles
and joints, which can result in joint deformities. Some
women with type 3 VWD experience prolonged bleeding during delivery.

Diagnosis
Diagnostic testing
Many people with VWD have mild symptoms or
symptoms that can be confused with other bleeding
disorders, making it difficult to diagnose VWD on the
basis of clinical symptoms. VWD should be suspected
in any person with a normal number of platelets in
their blood and bleeding from such mucous membranes as the nose, gums and gastrointestinal tract.
Testing for an individual with suspected VWD often
includes the measurement of:


how long it takes for the bleeding to stop after a tiny
cut is made in the skin (the bleeding time)



the amount of vWF (vWF antigen measurement)



the activity of vWF (ristocetin co-factor activity)



the amount of factor VIII (factor VIII antigen
measurement)



activity of factor VIII

Many doctors routinely screen women with
menorrhagia for VWD, as heavy menstrual bleeding
is the most common symptom of the disorder in
females.
People with type 1 VWD usually have an
increased bleeding time but they may have an intermittently normal bleeding time. They also have a
decreased amount of vWF, and decreased vWF activity and usually have slightly decreased factor VIII
3946

levels and activity. People with type 2 VWD have a
prolonged bleeding time, decreased activity of vWF
and may have decreased amounts of vWF and factor
VIII, and may have decreased factor VIII activity.
Type 3 individuals have undetectable amounts of
vWF, negligible vWF activity, factor VIII levels of
less than 5–10%, and significantly reduced factor
VIII activity. The activity of vWF is reduced for all
types of VWD, making it the most sensitive means of
identifying all three types of VWD. Patients with borderline results should be tested two to three times over
a three month period.
Once a patient is diagnosed with VWD, further
testing such as vWF multimer analysis and ristocetininduced platelet aggregation (RIPA) may need to be
performed to determine the subtype. Multimer analysis evaluates the structure of the vWF, and RIPA
measures how much ristocetin is required to cause
the clumping of platelets in a blood sample. The
vWF multimer analysis is able to differentiate people
with a structurally normal vWF (type 1) from people
with a structurally abnormal vWF (type 2) and is often
able to identify the subtype of patients with type 2
VWD. People with type 1 VWD usually have normal
to decreased RIPA concentrations. Depending on the
subtype, patients with type 2 VWD either have
increased or decreased RIPA. RIPA is usually absent
and the multimer analysis shows undetectable vWF in
people with type 3 VWD.
In some cases DNA testing can be a valuable
adjunct to biochemical testing. The detection of gene
alteration(s) can confirm a diagnosis and can determine the type and subtype of VWD. It can also help to
facilitate prenatal testing and testing of other family
members. Unfortunately, as of 2001, many people
with VWD possess DNA changes that are not detectable through DNA testing. A person who has a
mother, father, or sibling diagnosed with VWD should
undergo biochemical testing for VWD. If the relative
with VWD possesses a detectable gene change, then
DNA testing should also be considered.
Prenatal testing
If one parent has been diagnosed with an autosomal dominant form of VWD or both parents are
carriers for an autosomal recessive form of VWD, then
prenatal testing can be considered. If the parent with
an autosomal dominant form of VWD possesses a
detectable gene change or both parents who are carriers for an autosomal recessive form of VWD possess
detectable mutations, then DNA testing of their fetus
would be available. DNA testing can be performed
through amniocentesis or chorionic villus sampling.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment
VWD is most commonly treated by replacement
of vWF through the administration of blood products
that contain vWF or through treatment with desmopressin (DDAVP, 1-deamino-8-D-arginine vasopressin). DDAVP functions by increasing the amount of
factor VIII and vWF in the bloodstream. Treatment
with blood products or DDAVP may be started in
response to uncontrollable bleeding or may be administered prior to procedures such as surgeries or dental
work. The type of treatment chosen depends on the
type of VWD and a patient’s response to a preliminary
treatment trial.
Treatment with desmopressin
DDAVP is the most common treatment for people with type 1 VWD. About 80% of people with type
1 VWD respond to DDAVP therapy. Treatment with
DDAVP can also be used to treat some people with
type 2 VWD. Patients with Type 2B VWD should not
be treated with this medication since DDAVP can
induce dangerous platelet clumping. Type 3 VWD
should not be treated with DDAVP since this medication does not increase the level of vWF in type 3
patients. DDAVP should only be used in people who
have been shown to be responsive through a pre-treatment trial transfusion with this medication.
DDAVP can be administered intravenously or
through a nasal inhaler. DDAVP has relatively few
side effects although some people may experience
facial flushing, tingling sensations, and headaches
after treatment with this medication. Often treatment
with this medication is only required prior to invasive
surgeries or dental procedures.
Treatment with blood products
Patients who are unable to tolerate or are unresponsive to drug-based treatments are treated with
concentrated factor VIII obtained from blood products. Not all factor VIII concentrates can be used
since some do not contain enough vWF. The concentrate is treated to kill most viruses, although caution
should be used since not all types of viruses are
destroyed. If the factor VIII concentrates are unable
to manage a severe bleeding episode, then blood
GALE ENCYCLOPEDIA OF MEDICINE

products called cryoprecipitates, which contain concentrated amounts of vWF, or platelet concentrates
should be considered. Caution should be used when
treating with these blood products since they are not
treated to kill viruses.
Other treatments and precautions
Medications called fibrinolytic inhibitors can be
helpful in the control of intestinal, mouth, and nose
bleeding. Estrogens such as are found in oral contraceptives increase the synthesis of vWF and can sometimes be used in the long-term treatment of women
with mild to moderate VWD. Estrogens are also sometimes used prior to surgery in women with type 1
VWD. Some topical agents are available to treat
nose and mouth bleeds.
Endometrial ablation, or the removal of the lining
of the uterus by means of electrocautery or other
thermal methods, is sometimes recommended as a
treatment for menorrhagia associated with VWD.
This procedure appears to be successful in lowering
the amount of bleeding that these women experience
during their menstrual periods.
Patients with VWD should avoid taking aspirin,
ibuprofen, or other NSAIDs, which can increase their
susceptibility to bleeding. They should also inform
their dentist of their diagnosis, as many routine dental
procedures can cause bleeding from the gums. People
with severe forms of VWD should avoid activities that
increase their risk of injury such as contact sports.
Patients with type 3 VWD living in the United
States may wish to contact one of the 146 federally
funded Hemophilia Treatment Centers (HTCs) for
advice about prophylactic treatment and general follow-up.

Prognosis
The prognosis for VWD disease is generally fairly
good and most individuals have a normal lifespan.
The prognosis can depend, however on accurate diagnosis and appropriate medical treatment.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Menstrual Abnormalities and Abnormal Uterine
Bleeding.’’ Section 18, Chapter 235. In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Beers, Mark H., MD, and Robert Berkow, MD, editors.
‘‘Platelet Disorders.’’ Section 11, Chapter 133. In The
3947

Von Willebrand disease

If the DNA change in the parent(s) is unknown then
prenatal testing can sometimes be performed through
biochemical testing of blood obtained from the fetal
umbilical cord, which is less accurate and is associated
with a higher risk of pregnancy loss.

Von Willebrand disease

KEY TERMS
Amniocentesis—A procedure performed at 16-18
weeks of pregnancy in which a needle is inserted
through a woman’s abdomen into her uterus to
draw out a small sample of the amniotic fluid from
around the baby. Either the fluid itself or cells from
the fluid can be used for a variety of tests to obtain
information about genetic disorders and other medical conditions in the fetus.
Autosomal dominant—A pattern of genetic inheritance where only one abnormal gene is needed to
display the trait or disease.
Autosomal recessive—A pattern of genetic inheritance where two abnormal genes are needed to display the trait or disease.
Biochemical testing—Measuring the amount or
activity of a particular enzyme or protein in a sample
of blood or urine or other tissue from the body.
Carrier—A person who possesses a gene for an
abnormal trait without showing signs of the disorder.
The person may pass the abnormal gene on to
offspring.
Chorionic villus sampling (CVS)—A procedure used
for prenatal diagnosis at 10-12 weeks gestation.
Under ultrasound guidance a needle is inserted either
through the mother’s vagina or abdominal wall and a
sample of cells is collected from around the early
embryo. These cells are then tested for chromosome
abnormalities or other genetic diseases.
Chromosome—A microscopic thread-like structure
found within each cell of the body and consists of a
complex of proteins and DNA. Humans have 46
chromosomes arranged into 23 pairs. Changes in
either the total number of chromosomes or their
shape and size (structure) may lead to physical or
mental abnormalities.
Deoxyribonucleic acid (DNA)—The genetic material in cells that holds the inherited instructions for
growth, development, and cellular functioning.

Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS

Hilbert, L., A. B. Federici, L. Baronciani, et al. ‘‘A New
Candidate Mutation, G1629R, in a Patient with Type
2A von Willebrand’s Disease: Basic Mechanisms and
Clinical Implications.’’ Haematologica 89 (September
2004): 1128–1133.
3948

Desmopressin (DDAVP)—A drug used in the treatment of von Willebrand’s disease.
Diagnostic testing—Testing performed to determine
if someone is affected with a particular disease.
DNA testing—Analysis of DNA (the genetic component of cells) in order to determine changes in genes
that may indicate a specific disorder.
Endothelial cells—The cells lining the inner walls of
the blood vessels.
Factor VIII—A protein involved in blood clotting that
requires vWF for stability and long-term survival in
the bloodstream.
Gene—A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence
found on a section of DNA. Each gene is found on a
precise location on a chromosome.
Menorrhagia—Excessively heavy menstrual flow
with cycles of normal length. It is also called
hypermenorrhea.
Mutation—A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted
to offspring.
Platelets—Small disc-shaped structures that circulate
in the blood stream and participate in blood clotting.
Prenatal testing—Testing for a disease such as a
genetic condition in an unborn baby.
Protein—Important building blocks of the body,
composed of amino acids, involved in the formation
of body structures and controlling the basic functions
of the human body.
Skin hematoma—Blood from a broken blood vessel
that has accumulated under the skin.
von Willebrand factor (vWF)—A protein found in
the blood that is involved in the process of blood
clotting.

Pollak, Eleanor S., MD, and Steven Stein, MD. ‘‘von
Willebrand Disease.’’ eMedicine August 18, 2004.
<http://www.emedicine.com/med/topic2392.htm>.
Rubin, G., M. Wortman, and P. A. Kouides.
‘‘Endometrial Ablation for von Willebrand
Disease-Related Menorrhagia—Experience with
Seven Cases.’’ Haemophilia 10 (September 2004):
477–482.

GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American Society of Hematology (ASH). 1900 M Street,
NW, Suite 200, Washington, DC 20036. (202) 776-0544.
Fax: (202) 776-0545. H<http://
www.hematology.org>.
National Heart, Lung, and Blood Institute (NHLBI) Health
Information Center, P. O. Box 30105, Bethesda, MD
20824-0105. (301) 592-8573. Fax: (240) 629-3246.
<http://www.nhlbi.nih.gov>.
National Hemophilia Foundation. Soho Building, 110
Greene Street, Suite 406, New York, NY 10012. (212)
219-8180. <http://www.hemophilia.org/home.htm>.
OTHER

National Heart, Lung, and Blood Institute (NHLBI) Fact
Sheet. ‘‘What Is von Willebrand Disease?’’ <http://
www.nhlbi.nih.gov/health/dci/Diseases/vWD/
vWD_WhatIs.html>.

Lisa Maria Andres, MS, CGC
Rebecca J. Frey, PhD

VSD see Ventricular septal defect

Vulvar cancer
Definition
Vulvar cancer refers to an abnormal, cancerous
growth in the external female genitalia.

Description
Vulvar cancer is a rare disease that occurs mainly
in elderly women. The vulva refers to the external
female genitalia, which includes the labia, the opening
of the vagina, the clitoris, and the space between the
vagina and anus (perineum). There are two pairs of
labia (a Latin term meaning lips). The labia meet to
protect the openings of the vagina and the tube that
connects to the bladder (urethra). The outer, most
prominent folds of skin are called labia majora, and
the smaller, inner skin folds are called labia minora.
Vulvar cancer can affect any part of the female genitalia, but usually affects the labia.
GALE ENCYCLOPEDIA OF MEDICINE

Approximately 70% of vulvar cancers involve the
labia (usually the labia majora), 15% to 20% involve
the clitoris, and 15% to 20% involve the perineum.
For approximately 5% of the cases, the cancer is present at more than one location. For approximately
10% of the cases, so much of the vulva is affected by
cancer that the original location cannot be determined. Vulvar cancer can spread to nearby structures
including the anus, vagina, and urethra.
Most vulvar cancers are squamous cell carcinomas. Squamous cells are the main cell type of the skin.
Squamous cell carcinoma often begins at the edges of
the labia majora or labia minora or the area around
the vagina. This type of cancer is usually slow-growing
and may begin with a precancerous condition referred
to as vulvar intraepithelial neoplasia (VIN), or dysplasia. This means that precancerous cells are present in
the surface layer of skin.
Other, less common types of vulvar cancer are
melanoma, basal cell carcinoma, adenocarcinomas,
Paget’s disease of the vulva, and tumors of the connective tissue under the skin. Melanoma, a cancer that
develops from the cells that produce the pigment that
determines the skin’s color, can occur anywhere on the
skin, including the vulva. Melanoma is the second most
common type of vulvar cancer, and accounts for 5% to
10% of the cases. Half of all vulvar melanomas involve
the labia majora. Basal cell carcinoma, which is the
most common type of cancer that occurs on parts of
the skin exposed to the sun, very rarely occurs on the
vulva. Adenocarcinomas develop from glands, including the glands at the opening of the vagina (Bartholin’s
glands) that produce a mucus-like lubricating fluid.
Vulvar cancer is most common in women over 50
years of age. The median age at diagnosis is 65 to 70
years old. Additional risk factors for vulvar cancer
include having multiple sexual partners, cervical cancer, and the presence of chronic vaginal and vulvar
inflammations. This type of cancer is often associated
with sexually transmitted diseases.
Vulvar cancer is most common in women who are
between the ages of 65 and 75 years. In the United
States there are approximately 3,000 new cases of
vulvar cancer diagnosed each year. Vulvar cancer
accounts for only 1% of all cancers in women.
Approximately 5% of all gynecologic cancers occur
on the vulva. For unknown reasons, the incidence of
vulvar cancer seems to be rising.

Causes and symptoms
Cancer is caused when the normal mechanisms
that control cell growth become disturbed, causing
3949

Vulvar cancer

Shankar, M., C. A. Lee, C. A. Sabin, et al. ‘‘von Willebrand
Disease in Women with Menorrhagia: A Systematic
Review.’’ BJOG 111 (July 2004): 734–740.
Sumner, M., and J. Williams. ‘‘Type 3 von Willebrand
Disease: Assessment of Complications and Approaches
to Treatment—Results of a Patient and Hemophilia
Treatment Center Survey in the United States.’’
Haemophilia 10 (July 2004): 360–366.

Vulvar cancer

the cells to continually grow without stopping. This is
usually the result of damage to the DNA in the cell.
Although the cause of vulvar cancer is unknown, studies have identified several risk factors for vulvar cancer. These include:


Vulvar intraepithelial neoplasia (VIN). This abnormal growth of the surface cells of the vulva can
sometimes progress to cancer.



Infection with human papillomavirus (HPV). This
virus is sexually transmitted and can cause genital
warts. Although HPV DNA can be detected in most
cases of vulvar intraepithelial neoplasia, it is detected
in fewer than half of all cases of vulvar cancer.
Therefore, the link between HPV infection and vulvar cancer is unclear. As of 2001, it is theorized that
two classes of vulvar cancer exist: one that is associated with HPV infection and one that is not.



Herpes simplex virus 2 (HSV2). This sexually transmitted virus is also associated with increased risk for
vulvar cancer.



Cigarette smoking. Smoking in combination with
infection by HPV or HSV2 was found to be a particularly strong risk factor for vulvar cancer.



Infection with human immunodeficiency virus (HIV).
This virus, which causes AIDS, decreases the body’s
immune ability, leaving it vulnerable to a variety of
diseases, including vulvar cancer.



Chronic vulvar inflammation. Long term irritation
and inflammation of the vulva and vagina, which
may be caused by poor hygiene, can increase the
risk of vulvar cancer.



Abnormal Pap smears. Women who have had abnormal Pap smears are at an increased risk of developing
vulvar cancer.



Chronic immunosuppression. Women who have had
long-term suppression of their immune system
caused by disease (such as certain cancers) or medication (such as those taken after organ transplantation) have an increased risk of developing vulvar
cancer.

The hallmark symptom of vulvar cancer is itching
(pruritus), which is experienced by 90% of the women
afflicted by this cancer. The cancerous lesion is readily
visible. Unfortunately, because of embarrassment or
denial, it is not uncommon for women to delay medical assessment of vulvar abnormalities. Any abnormalities should be reported to a gynecologist.
If squamous cell vulvar cancer is present, it may
appear as a raised red, pink, or white bump (nodule).
It is often accompanied by pain, bleeding, vaginal
3950

discharge, and painful urination. Malignant melanoma
of the vulva usually appears as a pigmented, ulcerated
growth. Other types of vulvar cancer may appear as a
distinct mass of tissue, sore and scaly areas, or cauliflower-like growths that look like warts.

Diagnosis
A gynecological examination will be used to
observe the suspected area. During this examination,
the physician may use a special magnifying instrument
called a colposcope to view the area better.
Additionally, the area may be treated with a dilute
solution of acetic acid, which causes some abnormal
areas to turn white, making them easier to see. During
this examination, if any area is suspected of being
abnormal, a tissue sample (biopsy) will be taken. The
biopsy can be performed in the doctor’s office with the
use of local anesthetic. A wedge-shaped piece of tissue,
which contains the suspect lesion with some surrounding normal skin and the underlying skin layers and
connective tissue, will be removed. Small lesions will
be removed in their entirety (excisional biopsy). The
diagnosis of cancer depends on a microscopic analysis
of this tissue by a pathologist.
The diagnosis for vulvar cancer will determine how
advanced the cancer is and how much it has spread.
This is determined by the size of the tumor and how
deep it has invaded the surrounding tissue and organs,
such as the lymph nodes. It will also be determined if
the cancer has metastasized, or spread to other organs.
Tests used to determine the extent of the cancer include
x ray and computed tomography scan (CT scan).
Endoscopic examination of the bladder (cystoscopy)
and/or rectum (proctoscopy) may be performed if it is
suspected that the cancer has spread to these organs.

Treatment
Clinical staging
The International Federation of Gynecology and
Obstetrics (FIGO) has adopted a surgical staging system for vulvar cancer. The stage of cancer is determined after surgery. The previous clinical staging
system for vulvar cancer is no longer used. Vulvar
cancer is categorized into five stages (0, I, II, III, and
IV) which may be further subdivided (A and B) based
on the depth or spread of cancerous tissue. The FIGO
stages for vulvar cancer are:


Stage 0. Vulvar intraepithelial neoplasia.



Stage I. Cancer is confined to the vulva and perineum.
The lesion is less than 2 cm (about 0.8 in) in size.
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Stage II. Cancer is confined to the vulva and perineum. The lesion is larger than 2 cm (larger than
0.8 in) in size.



Stage III. Cancer has spread to the vagina, urethra,
anus, and/or the lymph nodes in the groin
(inguinofemoral).



Stage IV. Cancer has spread to the bladder, bowel,
pelvic bone, pelvic lymph nodes, and/or other parts
of the body.
Treatments

Treatment for vulvar cancer will depend on its
stage and the patient’s general state of health.
Surgery is the mainstay of treatment for most cases
of vulvar cancer.
SURGERY. The primary treatment for stage I and
stage II vulvar cancer is surgery to remove the cancerous lesion and possibly the inguinofemoral lymph
nodes. Removal of the lesion may be done by laser,
to burn off a minimal amount of tissue, or by scalpel
(local excision), to remove more of the tissue. The
choice will depend on the severity of the cancer. If a
large area of the vulva is removed, it is called a vulvectomy. Radical vulvectomy removes the entire
vulva. A vulvectomy may require skin grafts from
other areas of the body to cover the wound and
make an artificial vulva. Because of the significant
morbidity and the psychosexual consequences of radical vulvectomy, there is a trend toward minimizing the
extent of cancer excision. The specific inguinofemoral
lymph node that would receive lymph fluid from the
cancerous lesion, known as the sentinel node, may be
exposed for examination (lymph node dissection) or
removed (lymphadenectomy), especially in cases in
which the cancerous lesion has invaded to a depth of
more than 1 mm. Surgery may also be followed by
chemotherapy and/or radiation therapy to kill additional cancer cells.

Surgical treatment of stage III and stage IV vulvar
cancer is much more complex. Extensive surgery
would be necessary to completely remove the cancerous tissue. Surgery would involve excision of pelvic
organs (pelvic exenteration), radical vulvectomy, and
lymphadenectomy. Because this extensive surgery
comes with a substantial risk of complications, it
may be possible to treat advanced vulvar cancer with
minimal surgery by using radiation therapy and/or
chemotherapy as additional treatment (adjuvant
therapy).
An intraoperative technique that is used to identify the sentinel node in breast cancer and melanoma is
being applied to vulvar cancer. This technique, called
GALE ENCYCLOPEDIA OF MEDICINE

lymphoscintigraphy, is performed during surgical
treatment of vulvar cancer and allows the surgeon to
immediately identify the sentinel node. A radioactive
compound (technetium 99m sulfur colloid) is injected
into the cancerous lesion approximately two hours
prior to surgery. This injection causes little discomfort, so local anesthesia is not required. During surgery, a radioactivity detector is used to locate the
sentinel node and any other nodes to which cancer
has spread. Though still in the experimental stage,
vulvar lymphoscintigraphy shows promise in reducing
morbidity and hospital length of stay.
The most common complication of vulvectomy is
the development of a tumor-like collection of clear
liquid (wound seroma). Other surgical complications
include urinary tract infection, wound infection, temporary nerve injury, fluid accumulation (edema) in the
legs, urinary incontinence, falling or sinking of the
genitals (genital prolapse), and blood clots (thrombus).
RADIATION THERAPY. Radiation therapy uses
high-energy radiation from x rays and gamma rays
to kill the cancer cells. The skin in the treated area
may become red and dry and may take as long as a
year to return to normal. Fatigue, upset stomach,
diarrhea, and nausea are also common complaints of
women having radiation therapy. Radiation therapy
in the pelvic area may cause the vagina to become
narrow as scar tissue forms. This phenomenon,
known as vaginal stenosis, makes intercourse painful.
CHEMOTHERAPY. Chemotherapy uses anticancer
drugs to kill the cancer cells. The drugs are given by
mouth (orally) or intravenously. They enter the bloodstream and can travel to all parts of the body to kill
cancer cells. Generally, a combination of drugs is
given because it is more effective than a single drug
in treating cancer. The side effects of chemotherapy
are significant and include stomach upset, vomiting,
appetite loss, hair loss, mouth or vaginal sores, fatigue,
menstrual cycle changes, and premature menopause.
There is also an increased chance of infections.

Alternative treatment
Although alternative and complementary therapies are used by many cancer patients, very few controlled studies on the effectiveness of such therapies
exist. Mind-body techniques such as prayer, biofeedback, visualization, meditation, and yoga have not
shown any effect in reducing cancer but can reduce
stress and lessen some of the side effects of cancer
treatments. Clinical studies of hydrazine sulfate
found that it had no effect on cancer and even worsened the health and well-being of the study subjects.
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Vulvar cancer



Vulvar cancer

Prognosis

KEY TERMS
Adjuvant therapy—A treatment that is intended to
aid primary treatment. Adjuvant treatments for
vulvar cancer are radiation therapy and
chemotherapy.
Biopsy—Removal of a small piece of tissue for
microscopic examination. This is done under
local anesthesia and removed by either using a
scalpel or a punch, which removes a small cylindrical portion of tissue.
Colposcope—An instrument used for examination
of the vagina and cervix. Part of the instrument
includes a magnifying lens for better visualization.
Metastasis—The movement of cancer cells from
one area of the body to another. This occurs
through the blood vessels or the lymph vessels.
Pelvic exenteration—Surgical removal of the
organs of the true pelvis which includes the uterus,
vagina, and cervix.
Sentinel lymph node—The first lymph node to
receive lymph fluid from a tumor. If the sentinel
node is cancer-free, then it is likely that the cancerous cells have not metastasized.

Factors that are correlated with disease outcome
include the diameter and depth of the cancerous lesion,
involvement of local lymph nodes, cell type, HPV
status, and age of the patient. Vulvar cancers that are
HPV positive have a better prognosis than those that
are HPV negative. The 5-year survival rate is 98% for
stage I vulvar cancer and 87% for stage II vulvar
cancer. The survival rate drops steadily as the number
of affected lymph nodes increases. The survival rate is
75% for patients with one or two, 36% for those with
three or four, and 24% for those with five or six
involved lymph nodes. The previous statistics were
obtained from studies of patients who received surgical treatment only and cannot be used to determine
survival rates when adjuvant therapy is employed.
Vulvar cancer can spread locally to encompass the
anus, vagina, and urethra. Because of the anatomy of
the vulva, it is not uncommon for the cancer to spread
to the local lymph nodes. Advanced stages of vulvar
cancer can affect the pelvic bone. The lungs are the
most common site for vulvar cancer metastasis.
Metastasis through the blood (hematogenous spread)
is uncommon.

Prevention

One clinical study of the drug amygdalin (Laetrile)
found that it had no effect on cancer. Laetrile can be
toxic and has caused death. Shark cartilage, although
highly touted as an effective cancer treatment, is an
improbable therapy that has not been the subject of
clinical study.
The American Cancer Society has found that the
‘‘metabolic diets’’ pose serious risk to the patient. The
effectiveness of the macrobiotic, Gerson, and Kelley
diets and the Manner metabolic therapy has not been
scientifically proven. The FDA was unable to substantiate the anticancer claims made about the popular Cancell treatment.
There is no evidence for the effectiveness of most
over-the-counter herbal cancer remedies. However,
some herbals have shown an anticancer effect. As
shown in clinical studies, Polysaccharide krestin,
from the mushroom Coriolus versicolor, has significant effectiveness against cancer. In a small study,
the green alga Chlorella pyrenoidosa has been shown
to have anticancer activity. In a few small studies,
evening primrose oil has shown some benefit in the
treatment of cancer.
3952

The risk of vulvar cancer can be decreased by
avoiding risk factors, most of which involve lifestyle
choices. Specifically, to reduce the risk of vulvar cancer, women should not smoke and should refrain from
engaging in unsafe sexual behavior. Good hygiene of
the genital area to prevent infection and inflammation
may also reduce the risk of vulvar cancer.
Because vulvar cancer is highly curable in its early
stages, women should consult a physician as soon as a
vulvar abnormality is detected. Regular gynecological
examinations are necessary to detect precancerous
conditions that can be treated before the cancer
becomes invasive. Because some vulvar cancer is a
type of skin cancer, the American Cancer Society
also recommends self-examination of the vulva using
a mirror. If moles are present in the genital area,
women should employ the ABCD rule:


Asymmetry. A cancerous mole may have two halves
of unequal size.



Border irregularity. A cancerous mole may have
ragged or notched edges.



Color. A cancerous mole may have variations in color.



Diameter. A cancerous mole may have a diameter
wider than 6 mm (1/4 in).
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Vulvodynia

Resources

Vulvodynia

BOOKS

Bruss, Katherine, Christina Salter, and Esmeralda
Galan, editors. American Cancer Society’s Guide
to Complementary and Alternative Cancer
Methods. Atlanta: American Cancer
Society, 2000.
Eifel, Patricia, Jonathan Berrek, and James Thigpen.
‘‘Cancer of the Cervix, Vagina, and Vulva.’’ In
Cancer: Principles & Practice of Oncology, edited by
Vincent DeVita, Samuel Hellman, and Steven
Rosenberg. Philadelphia: Lippincott Williams &
Wilkins, 2001.
Garcia, Agustin, and J. Tate Thigpen. ‘‘Tumors of the Vulva
and Vagina.’’ In Textbook of Uncommon Cancer, edited
by D. Raghavan, M. Brecher, D. Johnson, N. Meropol,
P. Moots, and J. Thigpen. Chichester: John Wiley &
Sons, 1999.
Primack, Aron. ‘‘Complementary/Alternative Therapies in
the Prevention and Treatment of Cancer.’’ In
Complementary/Alternative Medicine: An EvidenceBased Approach., edited by John Spencer and Joseph
Jacobs. St. Louis: Mosby, 1999.
PERIODICALS

Grendys, Edward, and James Fiorica. ‘‘Innovations in the
Management of Vulvar Carcinoma.’’ Current Opinion
in Obstetrics and Gynecology 12 (February 2000):
15-20.

Definition
Vulvodynia is chronic pain of the vulva, the external or visible region of the female genitalia, in the
absence of vulvar or vaginal infection or skin disease.

Description
As with other types of chronic pain, vulvodynia
can have a significant impact on the quality of life. The
disease may interfere with daily activities including
sitting, walking, physical exercise, and social interactions. Sexual intercourse may be painful or impossible.
Vulvodynia can lead to exhaustion and depression. In
extreme cases a woman may become bedridden.
Classification systems
Vulvodynia has not been well-defined, in part
because it has not been well-studied. The symptoms
vary greatly in severity and the causes of the condition
are unknown. Thus vulvodynia is classified in different
ways.
Most often vulvodynia is subdivided into two
types:


vulvar vestibulitis syndrome (VVS), also called vulval vestibulitis or vulvar dysesthesia, is a localized
inflammation of the vestibule—the region immediately surrounding the opening of the vagina and the
urethra.



dysesthetic vulvodynia, also called generalized vulvodynia or generalized vulvar dysesthesia, usually is
defined as vulvar burning that has no obvious cause
and is not limited to the vestibule.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta,
GA 30329. (800) ACS-2345. <http://
www.cancer.org>.
Cancer Research Institute, National Headquarters. 681
Fifth Ave., New York, NY 10022. (800) 992-2623.
<http://www.cancerresearch.org>.
Gynecologic Cancer Foundation. 401 N. Michigan Ave.,
Chicago, IL 60611. (800) 444-4441 or (312) 644-6610.
<http://www.wcn.org/gcf>.
National Institutes of Health. National Cancer
Institute. 9000 Rockville Pike, Bethesda, MD
20982. (800) 4-CANCER. <http://
cancernet.nci.nih.gov>.
OTHER

Cancer Care News. July 3, 2001. <http://
www.cancercare.org>.
Quackwatch, Questionable Cancer Therapies. July 3, 2001.
<http://www.quackwatch.com>.

Cindy L. A. Jones, Ph.D.
Belinda Rowland, Ph.D.

Vulvitis see Vulvovaginitis
GALE ENCYCLOPEDIA OF MEDICINE

Some women appear to suffer from both types of
vulvodynia simultaneously.
An older classification system is still in use. It
distinguishes between vulvar vestibulitis and vulvodynia and subdivides vulvodynia into two major
categories:


organic vulvodynia, in which a cause can be
identified



essential vulvodynia, in which a cause cannot be
identified and which usually affects older women,
particularly women in their 60s.
Demographics

Females of any age can develop vulvodynia. A
2003 study suggested that up to 16% of women—or
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Vulvodynia

14 million American women—experience chronic vulvar pain lasting three months or longer at some point
in their lives. Approximately one-half of these women
seek treatment. There is conflicting evidence concerning the prevalence of vulvodynia among different ethnic and racial groups. The 2003 study found that
Hispanic women were much more likely to suffer
from the condition. The study also found that
women who experienced pain when first using a tampon were seven to eight times more likely to have
vulvodynia at some point in their lives. Between 10%
and 25% of women with interstitial cystitis—a bladder
condition that causes frequent urination with burning—also have symptoms of vulvodynia.
The prevalence of VVS is unknown but some
surveys have suggested that about 28% of women
have a history of vestibular pain. It has been estimated
that about 15% of women seeing private gynecologists
and about 1% of women visiting genitourinary medical clinics suffer from VVS. Dysesthetic vulvodynia is
more common in postmenopausal women and
younger women who have had back injuries.

Preliminary evidence suggested that women with vulvodynia might have distinctive vaginal microflora—
the various organisms that normally inhabit the
vagina. Another 2004 study found that women with
vulvodynia were more sensitive to pain in other parts
of their bodies and may process pain differently than
other women.
In a small subset of women VVS appears to be
associated with chronic yeast infections. Some
researchers have found an association between VVS
and high levels of oxalate in the urine. It also has been
suggested that genetic factors may increase a woman’s
susceptibility to chronic vestibular inflammation. In
contrast, many researchers believe that dysesthetic
vulvodynia is caused by nerve irritation or
inflammation.
ORGANIC VULVODYNIA. Organic vulvodynia—in
which a cause for the condition can be identified—
includes contact or allergic dermatitis and chemical
irritation commonly caused by:


perfumes



scented or deodorant soaps or laundry detergent

Causes and symptoms



shampoos

Causes



fabric softener

Suggested causes of vulvodynia include:



scented or dyed toilet paper



irritation or injury to the vulvar nerves



scented menstrual pads



hypersensitivity of nerves in the vulvar region



vulvar wipes or deodorants—‘‘feminine hygiene’’
products



an abnormal response of vulvar cells to environmental factors, including infection or injury



douches



sexual lubricants



spermicides



some medications that are used to treat vulvar
problems



synthetic underwear



excessive vaginal discharge



urine or feces.



irritation from oxalate in the urine



a localized hypersensitivity to the yeast Candida
albicans



frequent yeast infections (candidiasis)



genital warts caused by the human papillomavirus
(HPV)



genital rashes



an allergic reaction to environmental irritants



an autoimmune response to the body’s own
chemicals



chronic vulvar and vaginal yeast infections



recurrent infection with herpes simplex virus



frequent use of antibiotics



other viral or bacterial infections



laser treatment or surgery on the external genitalia



nerve irritation



irritation or spasms in the pelvic floor muscles that
support the bladder, uterus, and rectum.



injury from childbirth or vaginal/vulvar trauma.

A 2004 study found that women with vulvodynia
were more likely than other women to have group D
streptococcus (GDS) bacteria in their vaginas.
3954

Other causes of organic vulvodynia include:

Symptoms
GENERAL SYMPTOMS. Vulvodynia usually begins
suddenly and may last for months or years.

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In addition to burning, sensations of vulvodynia
often are described as:


irritation



stinging



rawness



aching



stretching



throbbing



sharp, knife-like pain.
VULVAR VESTIBULITIS. VVS symptoms are con-

fined to the vestibule and vary from mild to severe.
VVS often begins suddenly, following an infection or
trauma. Painful sexual intercourse may be the first
symptom. The intense itching and painful burning
can turn into chronic pain. Symptoms may occur
daily or only with sexual intercourse.
In addition to painful burning, typical VVS symptoms include:


an extremely tender, dry, or raw vestibule



stinging or irritation of the vestibule



a sensation of tight skin in the vestibule



redness of the vestibule



pain that is so severe as to preclude intercourse

The majority of women with VVS only have
symptoms during or after:


the vestibule is touched



sexual intercourse



tampon insertion



a gynecological examination



bicycle or horseback riding



jogging



wearing tight pants.

However in severe cases, sitting, walking, or no
movement at all can cause pain.

such as sexual intercourse or bicycle riding may
increase the discomfort.
Areas commonly affected by dysesthetic vulvodynia include:


hymen



introitus—the membranes surrounding the vaginal
opening



small or minor vestibular glands around the vaginal
opening



vulvovaginal (Batholin’s) glands located on each side
of the vaginal opening



paraurethral (Skene’s) glands located on each side of
the urethral opening



vestibule



labia minora or inner labia



labia majora or outer labia

Some women also experience pain in the clitoris,
the perineum, the mons pubis, the anus, the groin, and
the inner thighs.
ORGANIC VULVODYNIA. Symptoms of organic
vulvodynia caused by chronic yeast infection include
vulvar itching and burning, especially just before menstruation. Symptoms caused by recurrent herpes simplex virus are intermittent, often reoccurring with
stress and lasting for a few days to a week or more.
Symptoms of vulvodynia caused by nerve irritation
include pain that radiates from the vulva to the perineum, groin, and thighs, and may include lower back
pain.

Diagnosis
Vulvodynia is characterized by pain or burning
that lasts for more than three months with no apparent
skin lesions. Although sometimes the vulvar tissue is
inflamed, often it appears completely normal. Other
conditions that can cause chronic vulvar pain may
coexist with vulvodynia. Many women with vulvodynia are misdiagnosed for years. Women often are told
that they have a chronic yeast infection or a psychological disorder. It is not uncommon for women to visit
at least five doctors before vulvodynia is diagnosed.
To diagnose vulvodynia a healthcare provider
may:


take a medical history



inquire about symptoms, sexual activity, diet, feminine hygiene, and medications



examine the vulva and vaginal secretions for signs of
infection or a skin disorder

DYSESTHETIC VULVODYNIA. Women with dyses-

thetic vulvodynia have constant burning throughout
the genitalia or in different areas at different times.
Symptoms do not necessarily occur in response to
touch or pressure on the vulva, although activities
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3955

Vulvodynia

Although the symptoms and their severity vary
widely, a burning sensation within the female genitalia
is the most common symptom. The pain may be intermittent or constant and localized or generalized
throughout the pelvic region.

Vulvodynia

Symptoms of vulvodynia may be treated with:



perform a pelvic examination



take a vaginal culture to test for yeast or bacteria





use a Q-tip to determine the location and severity of
the pain

topical anesthetics such as viscous or liquid 5% lidocaine ointment (Xylocaine) for temporary relief



nerve blockers



use a magnifying glass to look for abnormalities



cortisone creams



perform a colposcopy—an examination with a special magnifying lens—to look for inflamed surface
blood vessels



topical estrogen cream



antihistamines, such as Atarax or Vistaril, that inhibit the release of histamines that can irritate mucous
membranes



physical and exercise therapy to strengthen and relax
the pelvic-floor muscles—called pelvic floor therapy—particularly if lower back problems are
present.



perform a tissue biopsy—the removal of a small piece
of tissue for microscopic examination—particularly
if skin lesions are present.
Vulvar vestibulitis

Women with VVS are more likely to have yeast
infections than the general population. A yeast infection must be treated before VVS can be diagnosed.
VVS can be diagnosed by a ‘‘touch test’’ with a cottontipped applicator to reveal extreme sensitivity at various points on the vestibule. In about two-thirds of
VVS cases these points have tiny red spots. Biopsies
for VVS generally show signs of chronic
inflammation.
Dysesthetic vulvodynia
Dysesthetic vulvodynia generally is diagnosed
after ruling out other causes of vulvar pain including:


yeast, bacterial, or viral infection



contact or allergic dermatitis



overuse of medications, particularly topical steroids



Vulvar vestibulitis
VVS often is treated first with a corticosteroid
ointment, such as triamcinolone or desoximetasone,
twice a week for one month. Corticosteroid treatment
requires careful monitoring because it can cause irritation or thinning of the skin. If this treatment fails, VVS
may be treated with the antidepressant amitriptyline
(Elavil) or the anticonvulsant gabapentin (Neurontin).
Initial dosages are low and can be increased steadily
until symptoms are relieved or side effects become
intolerable, up to a maximum daily dosage of 150 mg
of amitriptyline or 3200 mg of gabapentin.
Other treatments for VVS include:


interferon—an anti-viral drug—injected into the
vulva, particularly in women who also have human
papillomavirus

vulvar dermatoses caused by one of numerous skin
conditions and diseases



vestibulectomy—surgery to remove the vestibule and
hymen, usually as a last resort.



cyclic vulvovaginitis—burning or itching that recurs
at a particular stage of a woman’s menstrual cycle



Laser treatments the freeze the tissue have not
proved successful and may worsen VVS.



vulvovaginal atrophy due to estrogen deficiency in
postmenopausal women.

Treatment
There is no cure for vulvodynia and, because
there appear to be multiple causes for the disorder
and because individual women have unique symptoms, no single treatment is appropriate for all
women. A treatment may work for some women
and not for others and some treatments may cause
unacceptable side effects in some women. Women
with vulvodynia should stop using all topical medications, soaps, douches, and other products that may
cause irritation. Yeast infections may require longterm treatment.
3956

Dysesthetic vulvodynia
The most common treatments for dysesthetic vulvodynia are medications that treat nerve irritation and
pain throughout the body—tricyclic antidepressants
such as amitriptyline, nortriptyline (Pamelor), desipramine (Norpramin), and imipramine (Tofranil),
and anticonvulsants such as carbamazepine
(Tegretol) or gabapentin.

Alternative treatment
Alternative treatments for vulvodynia include:


biofeedback; sensitive detectors are available for use
on the vulva
GALE ENCYCLOPEDIA OF MEDICINE

acupuncture



summer squash



cognitive behavioral therapy



rhubarb



aerobic exercise



berries



cool or lukewarm sitz baths for relieving irritation
and burning



purple grapes



tangerines



douching with baking soda to relieve inflammation



chocolate



a compress of Aveeno—a powdered oatmeal bath
treatment, made with two tablespoons of Aveeno to
one quart of water—placed over the vulva three to
four times per day.



beer, beverage mixes, and tea

Low-oxalate diet
Those who believe that vulvodynia may be caused
by acidic, irritating oxalate crystals in the urine,
recommend trying a low-carbohydrate, low-oxalate
diet for three months to a year. The diet involves:


eliminating all high-oxalate foods—those with more
than 10 mg of oxalate per serving



limiting moderate oxalate-containing foods (2–10
mg per serving) to three servings per week



drinking 12–14 cups of water per day



taking calcium citrate without Vitamin D, such as
two Citracal tablets three times per day, approximately 45 minutes before eating.

Calcium citrate supplements decrease calcium
oxalate formation in the urine, suppress oxalate secretion, and decrease the acidity of the urine.
Foods that are high in oxalates include:

Vulvodynia



Prognosis
Vulvodynia sometimes disappears spontaneously.
It often improves over time regardless of treatment. In
some women treatment results in partial or complete
relief of symptoms, although it may take weeks,
months, or even years. Other women are never completely free of symptoms.
It has been reported that about 30% of VVS cases
improve with corticosteroid treatment and another
60% improve with amitriptyline or other tricyclic antidepressants. Vestibulectomy has the highest success
rate of any VVS treatment.

Prevention
Numerous suggestions have been made for preventing vulvodynia and for relieving symptoms and
preventing further irritation, including:


using soft, white or unbleached, unscented toilet tissue



using 100% cotton menstrual pads and tampons



avoiding shampoo in the vulvar region



avoiding bubble bath, feminine hygiene products, perfumed creams and soaps, petroleum jelly, and bath oils



washing the vulva frequently with cool or lukewarm
water



using a bidet



drying the perineum with a hair dryer on the cool
setting



all beans



wheat bran, wheat germ, and grits



white corn



all nuts and nut butters



greens including chard, kale, escarole, collards, and
spinach



celery



parsley and watercress



urinating before the bladder is full



green peppers





beets

rinsing the vulva with water from a squeeze bottle
after urination



tomato and vegetable soups





rutabaga

eating fiber from whole grains, fruits, and vegetables,
and psyllium products, such as Metamucil or
Konsyl, to prevent constipation



eggplant



drinking eight glasses of water daily



leeks





okra

sitting on a foam rubber donut and standing periodically when sitting for long periods



sweet potatoes



using relaxation techniques

GALE ENCYCLOPEDIA OF MEDICINE

3957

Vulvodynia

KEY TERMS
Colposcopy—The use of a special microscope—a
colposcope—to visualize the genitalia.
Contact dermatitis—Irritant dermatitis; direct skin
contact with a substance that causes inflammation
in some people.
Dysesthetic vulvodynia—Generalized vulvodynia;
generalized vulvar dysesthesia; essential vulvodynia; chronic vulvar pain not limited to the vulva for
which there is no apparent cause.



avoiding pantyhose and jeans



promptly removing wet bathing suits and exercise
clothing



washing clothes in a dermatologically approved
detergent, such as Purex or Clear, or baking soda
soap



double-rinsing underwear and other clothing that
contacts the vulva



avoiding fabric softener and dryer sheets.
Advice on physical activity includes:

Hymen—A membrane that partially or completely
covers the vaginal opening.
Interstitial cystitis—Chronic inflammation of the
bladder; sometimes associated with vulvodynia.



avoiding activities that put direct pressure on the
vulva, such as bicycle and horseback riding



limiting intense exercise that applies friction to the
vulva

Labia majora—Major lips; mounds of tissue forming the lateral boundaries of the vulva.
Labia minora—Minor lips; narrow folds of tissue
between the labia major, on either side of the urethral and vaginal openings.



applying a frozen gel pack wrapped in a towel after
exercising to relieve symptoms



performing stretching and relaxation exercises such
as yoga



avoiding hot tubs and highly-chlorinated swimming
pools.

Mons pubis—The fatty tissue over the area where
the pubic bones meet.
Organic vulvodynia—Chronic vulvar pain for
which a cause can be identified.
Oxalate—A salt of oxalic acid produced by the
body’s metabolism and excreted in the urine.
Perineum—The area between the external genitalia and the anus.
Tricyclic antidepressants—Medications used to
treat mental depression and other conditions
including chronic pain.
Vestibule—Vestibule of vulva; vestibule of vagina;
the space between the labia minor containing the
openings of the vagina and urethra.
Vestibulectomy—Surgical removal of the vestibule
and hymen.
Vulva—Pendum; the external female genitalia
including the mons pubis, labia majora and minor,
clitoris, vestibule, glands, and the vaginal opening.
Vulvar vestibulitis syndrome; VVS—Vulval vestibulitis; vulvar dysesthesia; inflammation of the
vestibule.

Suggestions for clothing and laundry include:


wearing all-white cotton underwear and washing
new underwear before use



wearing loose-fitting skirts and pants

3958

Suggestions for sexual intercourse include:


applying a topical anesthetic, such as 5% lidocaine
gel, to the vestibule 10–15 minutes before intercourse



using pure almond oil, vegetable oil, or a watersoluble, glycerin-containing lubricant such as
Astroglide, applied at the initiation of sexual activity



avoiding lubricants containing preservatives or other
chemicals



avoiding contraceptive creams, spermicides, and
devices that may irritate the vulva



applying ice or a frozen blue gel pack after intercourse to prevent burning



urinating and rinsing the vulva with cool water after
intercourse.

Resources
BOOKS

Glazer, Howard I., and Gae Rodke. The Vulvodynia Survival
Guide: How to Overcome Painful Vaginal Symptoms and
Enjoy an Active Lifestyle. Oakland, CA: New
Harbinger Publications, 2002.
Stewart, Elizabeth G., and Paula Spencer. The V Book: A
Doctor’s Guide to Complete Vulvovaginal Health. New
York: Bantam, 2002.
PERIODICALS

Cool, Lisa Collier. ‘‘Betrayed by Her Body.’’ Good
Housekeeping 239, No. 3 (September 2004): 70–1.
GALE ENCYCLOPEDIA OF MEDICINE

ORGANIZATIONS

American College of Obstetricians and Gynecologists.
409 12th St., S.W., PO Box 96920, Washington,
D.C. 20090-6920. 202-638-5577. <http://
www.acog.org>.
Center for Vulvar Diseases, Department of Obstetrics and
Gynecology, University of Michigan Health System.
1500 E. Medical Center Drive, Taubman Center,
Reception E, Box 0384, Ann Arbor, MI 48109-0384.
734-936-4000. <http://www.med.umich.edu/obgyn/
vulva/index.htm>.
National Vulvodynia Association. P.O. Box 4491, Silver
Spring, MD 20914-4491. 301-299-0775. <http://
www.nva.org>.
Vulvar Pain Foundation. P.O. Drawer 177, Graham, NC,
27253. 336-226-0704. <http://
www.vulvarpainfoundation.org>.
OTHER

About Vulvodynia. National Vulvodynia Association.
June 19, 2003 [cited March 5, 2005]. <http://
www.nva.org/about_vulvodynia/
what_is_vulvodynia.html>.
‘‘Chronic Vulvar Pain May Be a Highly Prevalent
Disorder.’’ NVA News. National Vulvodynia
Association. April 14, 2003 [cited March 5,
2005]. <http://www.nva.org/nva_newsletter/
harlow.html>.
‘‘Fact Sheet.’’ Media Center. National Vulvodynia
Association. November 4, 2002 [cited February 21,
2005]. <http://www.nva.org/media_corner/
fact_sheet.html>.
‘‘Self-Help Tips for Vulvar Skin Care.’’ Patient Services.
National Vulvodynia Association. November 4, 2002
[cited March 5, 2005]. <http://www.nva.org/patient_
services/Self_Help_Tips.html>.
‘‘Vulvar Pain.’’ Related Diseases. Interstitial Cystitis
Association. November 1, 2004 [cited February 22,
2005]. <http://www.ichelp.org/RelatedDiseases/
VulvarPain.html>.
Vulvodynia. familydoctor.org. August 2004 [cited
February 21, 2005]. <http://familydoctor.org/
367.xml>.
‘‘Vulvodynia and Vulvar Vestibulitis.’’ Center for Vulvar
Diseases. Department of Obstetrics and Gynecology,
University of Michigan Health System. 2005 [cited
February 22, 2005]. <http://www.med.umich.edu/
obgyn/vuvla/vulvodyn.htm>.

Margaret Alic, Ph.D.
GALE ENCYCLOPEDIA OF MEDICINE

Vulvovaginitis
Definition
Inflammation of the vagina and vulva most often
caused by a bacterial, fungal, or parasitic infection.

Description
Vulvovaginitis, vulvitis, and vaginitis are general
terms that refer to the inflammation of the vagina and/
or vulva (the external genital organs of a woman).
These conditions can be caused by bacterial, fungal,
or parasitic infections. Also, vulvovaginitis can be
caused by low estrogen levels (called ‘‘atrophic vaginitis’’) or any type of allergic or irritation response from
things such as spermicidal products, condoms, soaps,
and bubble bath.
In general, vulvovaginitis causes vaginal discharge, irritation, and itching. One of the most common reasons why women visit their doctor is because
of a change in vaginal discharge. It is completely normal for a woman to have a vaginal discharge, the
amount and consistency of which varies during the
course of the menstrual cycle. Each of the three most
common types of vulvovaginitis will be described
separately.
Bacterial vaginosis
Bacterial vaginosis is the most common cause of
vaginitis during the childbearing years. Forty percent
to 50% of vaginitis cases are caused by bacterial vaginosis. The occurrence of bacterial vaginosis is difficult
to determine but studies have proposed that 10%–
41% of women have had it at least once. The occurrence of bacterial vaginosis in the United States is
highest among African-American women and
women who have had multiple sexual partners and
lowest among Asian women and women with no history of sexual contact with men. Bacterial vaginosis is
not considered a sexually transmitted disease although
it can be acquired by sexual intercourse.
Bacterial vaginosis is not caused by a particular
organism but is a change in the balance of normal
vaginal bacteria. Ninety percent of the bacteria
found in a healthy vagina belong to the Lactobacillus
family. For unknown reasons, there is a shift in the
bacterial population that results in overgrowth of
other bacteria. Patients suffering from bacterial vaginosis have very high numbers of such bacteria as
Gardnerella
vaginalis,
Mycoplasmahominis,
Bacteroides species, and Mobiluncus species. These
3959

Vulvovaginitis

Lotery, Helen E., et al. ‘‘Vulvodynia.’’ Lancet 363, no. 9414
(March 27, 2004): 1058–60.
‘‘Vulvodynia; Genital Pain Linked to Increased Pain
Sensitivity Throughout the Body.’’ Women’s Health
Weekly August 5, 2004: 112.

Vulvovaginitis

bacteria can be found at numbers 100 to 1000 times
greater than found in the healthy vagina. In contrast,
Lactobacillus bacteria are in very low numbers or
completely absent from the vagina of women with
bacterial vaginosis.
Candida vulvovaginitis
Candida vulvovaginitis also has been called ‘‘vulvovaginal candidiasis,’’ ‘‘candidal vaginitis,’’ ‘‘monilial infection,’’ or ‘‘vaginal yeast infection.’’ Twenty to
25% of the vaginitis cases are Candida vulvovaginitis.
It has been estimated that about 75% of all women get
a vaginal yeast infection at least once. In 80–90% of
the cases, Candida vulvovaginitis is caused by an overgrowth of the yeast Candida albicans. The remaining
cases are caused by other species of Candida. It is not
known what causes the yeast overgrowth. However,
antibiotics can inadvertently kill normal bacteria in the
vagina and cause an overgrowth of Candida.
Candida vulvovaginitis is not considered a sexually transmitted disease because Candida species are
commonly found in the healthy vagina. It is a rare
disease in girls before puberty and celibate women.
Vaginal yeast infections tend to occur more frequently
in women who are pregnant, diabetic and not controlling their disease, taking birth control pills, or taking
antibiotics. The stress of military deployment has also
been found to be a factor in triggering vaginal yeast
infections. Some women have four or more attacks per
year, a condition called ‘‘recurrent vaginal
candidiasis.’’
Trichomoniasis
Trichomoniasis, which is sometimes called ‘‘trich,’’
accounts for 15–20% of the cases of vaginitis. It is
estimated that two million to three million American
women get trichomoniasis each year, and as many as
120 million women worldwide. Unlike the previous
two causes of vulvovaginitis, trichomoniasis is a sexually transmitted disease. This means that the disease is
passed from person to person only by sexual contact.
Trichomoniasis occurs in both men and women and is
caused by infection with the single-celled parasite
Trichomonas vaginalis. Infection with Trichomonas
vaginalis is frequently associated with other sexually
transmitted diseases and assists the spread of the AIDS
virus.

Causes and symptoms
Vulvovaginitis is most often caused by a bacterial,
fungal, or parasitic infection as described above. Other
3960

microorganisms may cause vulvovaginitis, or it may
be caused by allergic reaction, irritation, injury, low
estrogen levels, and certain diseases. Risk factors for
bacterial vaginosis include using an intrauterine device
(IUD), non-white race, prior pregnancy, first sexual
activity at an early age, having multiple sexual partners, and having a history of sexually transmitted diseases. Persons at an increased risk for Candida
vulvovaginitis include those who have had previous
candida infections, frequent sexual intercourse, use
birth control pills, have AIDS, are pregnant, are taking antibiotics or corticosteroids, are diabetic, use
douches, use perfumed feminine hygiene sprays, wear
tight clothing, or use vaginal sponges or an IUD.
The typical symptoms of vulvovaginitis are: vaginal discharge, itching, and irritation. Women may
have few or no symptoms, while others may have
pronounced symptoms. The main symptom of bacterial vaginosis is a fishy-smelling, thin, milky-white or
gray vaginal discharge but itching and burning may
also be present. The fishy smell is stronger after sexual
intercourse. The symptoms of candida vulvovaginitis
are itching, soreness, painful sexual intercourse, and a
thick, curdy, white (like cottage cheese) vaginal discharge. Trichomoniasis symptoms are: painful urination, painful sexual intercourse, and a yellow-green to
gray, foul smelling, sometimes frothy, vaginal
discharge.

Diagnosis
Vulvovaginitis can be diagnosed and treated by a
nurse practitioner or physician. Most insurance companies cover the costs of diagnosis and treatment. To
diagnose vulvovaginitis, the doctor will examine the
vagina (using a speculum to keep the vagina open) and
take a sample of the vaginal discharge for tests and
microscopic analysis. Laboratory culture results
should be available in two to three days but the microscopic examination of the vaginal discharge may be
immediately performed in the doctor’s office.
Diagnosis may be difficult because there are many
different causes of vulvovaginitis. Women who think
that they have vulvovaginitis should always visit their
doctor to get an accurate diagnosis. Many women
assume that they have a yeast infection and take
over-the-counter medicines without first consulting
their doctors.
There are four signs that indicate that a woman
has bacterial vaginosis. These signs (known as Amsel’s
criteria) are: a thin, milky white discharge that clings
to the walls of the vagina, presence of a fishy odor, a
vaginal pH greater than 4.5, and the presence of clue
GALE ENCYCLOPEDIA OF MEDICINE

Trichomoniasis tends to be underdiagnosed in
men because of the relative mildness of symptoms in
men and insufficiently sensitive diagnostic tests. The
recent introduction of DNA amplification, however,
indicates that the incidence of trichomoniasis in men is
much higher than was previously thought.

Treatment
Both bacterial vaginosis and trichomoniasis
require prescription medication for treatment.
Candida vulvovaginitis may be treated with either
prescription or over-the-counter medicines. It is not
advisable to take over-the-counter vaginal yeast infection medicines if one does not have a yeast infection.
An Institute of Epidemiological Research survey of
390 gynecologists found that 44% of the women who
were diagnosed with bacterial vaginosis had first treated themselves with over-the-counter yeast infection
medications.
Bacterial vaginosis should be treated daily for one
week with the antibiotics metronidazole (Flagyl,
Protostat) or clindamycin (Cleocin) either as pills
taken orally or in a gel or cream form put into the
vagina. Trichomoniasis is treated with either a large,
single dose of metronidazole or with a smaller dose
taken twice daily for one week. Male sexual partners
of women with trichomoniasis also must be treated.
Candida vulvovaginitis is most often treated by
the application of medicated gels, creams, or suppositories applied directly to the vagina. The antifungal
drugs used to treat candida vulvovaginitis include oral
fluconazole (Diflucan), butoconazole (Femstat), clotrimazole (Gyne-lotrimin, Mycelex), miconazole
(Monistat), and ticonazole (Vagistat). Most require
only one or a few days of therapy to be effective.
Women who have recurrent Candida infections may
receive treatment for several weeks and then some
form of a long-term preventative treatment.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Parasite—An animal or plant that can only survive
by living inside or upon another animal or plant.
Vulva—The external genital organs of a woman,
including the outer and inner lips, clitoris, and
opening of the vagina.

Alternative treatment
One of the primary focuses of alternative treatment for vaginal conditions including vulvovaginitis is
rebalancing the normal vaginal flora. To assist with
this rebalancing, Lactobacillus acidophilus and L. bifidus are recommended, either taken internally or introduced directly into the vagina. Garlic (Allium sativum),
both taken internally and inserted into the vagina (a
peeled whole clove wrapped in gauze), may be helpful
due to its antibacterial and antifungal actions. A variety of other herbs can be used as douches or in suppository form to help treat acute flare-ups of vaginal
symptoms. For example a douche made by steeping
1–2 tsp. of calendula (Calendula officinalis) in boiling
water (let the water cool before using) may help reduce
inflammation. A boric acid douche can help to acidify
the vaginal pH so that unwanted bacteria cannot survive and multiply. For atrophic vaginitis, especially in
menopausal women, topical application of progesterone cream can help with symptoms caused by thinning
of the tissue lining the vagina.
Dietary modification and nutritional supplementation may also be helpful in the treatment of vulvovaginitis. Antioxidant vitamins, including A, C, and E,
as well as B complex vitamins, and vitamin D, are
recommended. Foods to avoid include cheese, alcohol,
chocolate, soy sauce, sugar, vinegar, fruits, and any
fermented foods. Wearing cotton underwear and loose
fitting clothes and avoiding panty hose can help keep
the vagina cool and dry, thus helping to prevent some
forms of vulvovaginitis. Cases of chronic vulvovaginitis should be addressed on systemic level by an alternative practitioner.

Prognosis
Vulvovaginitis is a disease with minor symptoms
and most women respond well to medications. It is
believed that certain vaginal infections, if left
untreated, can lead to more serious conditions such
as pelvic inflammatory disease, endometritis, postsurgical infections, and spread of the AIDS virus.
3961

Vulvovaginitis

cells in the vagina. Clue cells are vaginal cells that are
covered with small bacteria. A diagnosis of candida
vulvovaginitis is made after finding a normal vaginal
pH (4 to 4.5) and the presence of many yeast cells in
the sample of vaginal discharge or growth of yeast
on laboratory media. In the spring of 2004, the U.S.
Food and Drug Administration (FDA) cleared a new
quick test to diagnose trichnomonas infection. The
test provides results in 10 minutes. The company that
manufactures the test also has a rapid result test to
bacterial vaginosis. A trichomoniasis diagnosis is
made when the parasites are found in the vaginal
discharge either by microscopic examination or in
laboratory cultures.

Vulvovaginitis

Prevention
Vaginal infections may be prevented by following
these suggestions:


Over-the-counter yeast infection treatments should
not be taken unless the woman had been diagnosed
with candidiasis before and recognizes the symptoms.



Douching should be avoided because it may disturb
the balance of organisms in the vagina and may
spread them higher into the reproductive system.



Thoroughly dry oneself after bathing and remove a
wet bathing suit promptly.



Avoid wearing tight clothing and wear cotton
underwear.



Clean diaphragms, cervical caps, and spermicide
applicators after use. Use condoms to avoid sexually
transmitted disease.



After a bowel movement, wipe from front to back to
avoid spreading intestinal bacteria to the vagina.

Resources
BOOKS

Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Part II, ‘‘CAM Therapies for Specific Conditions:
Vaginitis.’’ New York: Simon & Schuster, 2002.
PERIODICALS

Ching, Susanne, and Phuong H. Nguyen. ‘‘Vaginitis.’’
eMedicine April 5, 2002. <http://emedicine.com/med/
topic2358.htm>.
Cohn, S. E., and R. A. Clarke. ‘‘Sexually Transmitted
Diseases, HIV, and AIDS in Women.’’ Medical Clinics
of North America 87 (September 2003): 971–995.
Dunne, R. L., L. A. Dunn, P. Upcroft, et al. ‘‘Drug
Resistance in the Sexually Transmitted Protozoan

3962

Trichomonas vaginalis.’’ Cell Research 13 (August
2003): 239–249.
‘‘Fast Tests for Trichomonas and BV.’’ Contemporary OB/
GYN May 2004: 32–34.
Lowe, N. K., and N. A. Ryan-Wenger. ‘‘Military Women’s
Risk Factors for and Symptoms of Genitourinary
Infections During Deployment.’’ Military Medicine 168
(July 2003): 569–574.
Pirotta, M. V., J. M. Gunn, and P. Chondros. ‘‘‘Not Thrush
Again!’ Women’s Experience of Post-Antibiotic
Vulvovaginitis.’’ Medical Journal of Australia 179 (July
7, 2003): 47–49.
Schwebke, J. R., and E. W. Hook, 3rd. ‘‘High Rates of
Trichomonas vaginalis Among Men Attending a
Sexually Transmitted Diseases Clinic: Implications for
Screening and Urethritis Management.’’ Journal of
Infectious Diseases 188 (August 1, 2003): 465–468.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 6393311. <http://www.cdc.gov>.
National Vaginitis Association. 117 South Cook St., Suite
315, Barrington, IL 60010. (800) 909-8745.
VagAssoc@aol.com. <http://
www.vaginalinfections.org>.
OTHER

Centers for Disease Control and Prevention (CDC). ‘‘Fact
Sheet: Trichomonas Infection.’’ <http://www.cdc.gov/
ncidod/dpd/parasites/trichomonas/
factsht_trichomonas.htm>.
Women’s Health STD Information Center. JAMA. <http://
pubs.ama-assn.org>.

Belinda Rowland, PhD
Rebecca J. Frey, PhD
Teresa G. Odle

GALE ENCYCLOPEDIA OF MEDICINE

W

Waldenströ disease see Waldenström’s
macroglobulinemia

Waldenström’s
macroglobulinemia
Definition
Waldenstrom’s macroglobulinemia is a rare,
chronic cancer of the immune system that is characterized by hyperviscosity, or thickening, of the blood.

Description
Waldenstrom’s (Waldenstrom, Waldenstroem’s)
macroglobulinemia (WM) is a lymphoma, or cancer
of the lymphatic system. It was first identified in 1944,
by the Swedish physician Jan Gosta Waldenstrom, in
patients who had a thickening of the serum, or liquid
part, of the blood. Their blood serum contained a
great deal of a very large molecule called a globulin.
Thus, the disorder is called macroglobulinemia.
Lymphomas are cancers that originate in tissues
of the lymphatic system. All lymphomas other than
Hodgkin’s disease, including WM, are known collectively as non-Hodgkin’s lymphomas. There are 13
major types of non-Hodgkin’s lymphomas, and others
that are very rare. Other names that are sometimes
used for WM include: lymphoplasmacytic lymphoma,
lymphoplasmacytic leukemia, macroglobulinemia
of Waldenstrom, primary macroglobulinemia,
Waldenstrom’s syndrome, Waldenstrom’s purpura,
or hyperglobulinemic purpura. Purpura refers to purple spots on the skin, resulting from the frequent
bleeding and bruising that can be a symptom of WM.
GALE ENCYCLOPEDIA OF MEDICINE

WM is classified as a low-grade or indolent
form of lymphoma because it is a slow-growing
cancer that produces fewer symptoms than other
types of lymphomas. WM most often affects males
over the age of 65. Frequently, this disease produces
no symptoms and does not require treatment. It has
not been studied as extensively as other types of
lymphoma.
The lymphatic system
The lymphatic system is part of the body’s
immune system, for fighting disease, and part of the
blood-producing system. It includes the lymph vessels
and nodes, and the spleen, bone marrow, and thymus.
The narrow lymphatic vessels carry lymphatic fluid
from throughout the body. The lymph nodes are
small, pea-shaped organs that filter the lymphatic
fluid and trap foreign substances, including viruses,
bacteria, and cancer cells. The spleen, in the upper left
abdomen, removes old cells and debris from the blood.
The bone marrow, the spongy tissue inside the bones,
produces new blood cells.
B lymphocytes or B cells are white blood cells that
recognize disease-causing organisms. They circulate
throughout the body in the blood and lymphatic
fluid. Each B lymphocyte recognizes a specific foreign
substance, or antigen. When it encounters its specific
antigen, the B cell begins to divide and multiply, producing large numbers of identical (monoclonal),
mature plasma cells. These plasma cells produce
large amounts of antibody that are specific for the
antigen. Antibodies are large proteins called immunoglobulins (Igs) that bind to and remove the specific
antigen.
A type of Ig, called IgM, is part of the early
immune response. The IgM molecules form clusters
3963

Waldenström’s macroglobulinemia

in the bloodstream. When these IgM clusters encounter their specific antigen, usually a bacterium, they
cover it so that it can be destroyed by other immune
system cells.
Plasma cell neoplasm
WM is a type of plasma cell neoplasm or B-cell
lymphoma. These are lymphomas in which certain
plasma cells become abnormal, or cancerous, and
begin to grow uncontrollably. In WM, the cancerous
plasma cells overproduce large amounts of identical
(monoclonal) IgM antibody. This IgM also is called M
protein, for monoclonal or myeloma protein.
Macroglobulinemia refers to the accumulation of
this M protein in the serum of the blood. This large
amount of M protein can cause the blood to thicken,
causing hyperviscosity. The malignant plasma cells of
some WM patients also produce and secrete partial
immunoglobulins called light chains, or Bence-Jones
proteins. The malignant plasma cells can invade various tissues, including the bone marrow, lymph nodes,
and spleen, causing these tissues to swell.
WM accounts for about 1-2% of non-Hodgkin’s
lymphomas. It is estimated that it may affect about
five out of every 100,000 people. It usually affects
people over the age of 50, and most often develops
after age 65. It is more common in men than in women.
In the United States, WM is more common among
Caucasians than among African Americans. The disease can run in families.



nose bleeds



gastrointestinal bleeding



weight loss



night sweats



increased and recurrent infections



poor blood circulation in the extremities

Poor blood circulation, or Raynaud’s phenomenon, can affect any part of the body, but particularly
the fingers, toes, nose, and ears.
Cold weather can cause additional circulatory
problems, by further thickening the blood and slowing
down circulation. In some cases, the excess blood
protein may precipitate out of the blood in the cold,
creating particles that can block small blood vessels.
This is called cryoglobulinemia. The extremities may
turn white, or a patchy red and white. The hands, feet,
fingers, toes, ears, and nose may feel cold, numb, or
painful.
Hyperviscosity may affect the brain and nervous
system, leading to additional symptoms. These symptoms include:


peripheral neuropathy, caused by changes in the
nerves, leading to pain or numbness in the extremities



dizziness



headaches



vision problems or loss of vision



Mental confusion



poor coordination

Causes and symptoms



temporary paralysis

The cause of WM is not known.



mental changes

Many individuals with WM have no symptoms of
the disease. This is known as asymptomatic macroglobulinemia. When symptoms of WM are present, they
may vary greatly from one individual to the next.
Hyperviscosity syndrome
At least 50% of individuals with WM have hyperviscosity syndrome, an increased viscosity or thickening of the blood caused by the accumulation of IgM in
the serum. Hyperviscosity can cause a slowing in the
circulation through small blood vessels. This condition can lead to a variety of symptoms:


fatigue



weakness



rash



bruising

3964

Hyperviscosity can clog the tubules that form the
filtering system of the kidneys, leading to kidney
damage or kidney failure. Existing heart conditions
can be aggravated by WM. In extreme cases, WM
may result in heart failure. Late-stage WM also may
lead to mental changes that can progress to coma.
Anemia
The accumulation of IgM in the blood causes
an increase in the volume of the blood plasma. This
effectively dilutes out the red blood cells and other
blood components. The lowered concentration of red
blood cells can lead to anemia and cause serious fatigue. Likewise, a deficiency in platelets (thrombocytopenia), which cause the blood to clot, can result in easy
bleeding and bruising. As the cancer progresses, there
may be abnormal bleeding from the gums, nose,
mouth, and intestinal tract. There may be bluish
GALE ENCYCLOPEDIA OF MEDICINE

cells. However, less than 5% of patients with WM
have lytic bone lesions, caused by cancerous plasma
cells in the bone marrow that are destroying healthy
cells. Bone lesions can be detected with x rays.

Organ involvement
In 5-10% of WM cases, the IgM may be deposited
in tissues. Thus, some individuals with WM have
enlargement of the lymph nodes, the spleen, and/or
the liver.
If Bence-Jones proteins are produced by the
malignant plasma cells, they may be deposited in the
kidneys. There they can plug up the tiny tubules that
form the filtering system of the kidneys. This can lead
to kidney damage and kidney failure.

Diagnosis
Since many individuals with WM have no symptoms, the initial diagnosis may result from blood tests
that are performed for some other purpose. Blood cell
counts may reveal low red blood cell and platelet
levels. A physical examination may indicate enlargement of the lymph nodes, spleen, and/or liver. A retinal eye examination with an ophthalmoscope may
show retinal veins that are enlarged or bleeding.
Blood and urine tests
Serum protein electrophoresis is used to measure
proteins in the blood. In this laboratory procedure,
serum proteins are separated in an electrical field,
based on the size and electrical charge of the proteins.
Serum immunoelectrophoresis uses a second antibody
that reacts with IgM. A spike in the Ig fraction indicates a large amount of identical or monoclonal IgM
in individuals with WM.
Normal serum contains 0.7-1.6 gm per deciliter
(g/dl) of Ig, with no monoclonal Ig present. At serum
IgM concentrations of 3-5 g/dl, symptoms of hyperviscosity often are present. However some individuals remain asymptomatic with IgM levels as high
as 9 g/dl.
Urinalysis may indicate protein in the urine. A
urine Bence-Jones protein test may indicate the presence of these small, partial Igs.

Treatment
Clinical staging, to define how far a cancer has
spread through the body, is the common method for
choosing a cancer treatment. However, there is no
generally-accepted staging system for WM.
There also is no generally-accepted course of
treatment for WM. Treatment may not be necessary
for asymptomatic macroglobulinemia. However, if
IgM serum levels are very high, treatment may be
initiated even in the absence of symptoms. If symptoms are present, treatment is directed at relieving
symptoms and retarding the disease’s development.
Of major concern is the prevention or alleviation of
blood hyperviscosity. Therefore, the initial treatment
depends on the viscosity of the blood at diagnosis.
Hyperviscosity
Plasmapheresis, or plasma exchange transfusion,
is a procedure for thinning the blood. In this treatment, blood is removed and passed through a cell
separator that removes the plasma, containing the
IgM, from the red and white blood cells and platelets.
The blood cells are transfused back into the patient,
along with a plasma substitute or donated plasma.
Plasmapheresis relieves many of the acute symptoms
of WM. Individuals with WM may be given fluid to
counter the effects of hyperviscous blood.
Low blood cell counts
Treatments for low blood cell levels include:


the drug Procrit to treat anemia



transfusions with packed red blood cells to treat
anemia in later stages of the disease



antibiotics to treat infections caused by a deficiency
in white blood cells



transfusions with blood platelets
Chemotherapy

Bone marrow
Abnormal blood tests usually are followed by a
bone marrow biopsy. In this procedure, a needle is
inserted into a bone and a small amount of marrow
is removed. Microscopic examination of the marrow
may reveal elevated levels of lymphocytes and plasma
GALE ENCYCLOPEDIA OF MEDICINE

Chemotherapy, the use of anti-cancer drugs, helps
to slow the abnormal development of plasma cells, but
does not cure WM. It can reduce the amount of IgM in
the bone marrow. In particular, chemotherapy is used
to treat severe hyperviscosity and anemia that are
caused by WM.
3965

Waldenström’s macroglobulinemia

discoloration of the skin. In the later stages of the
disease, leukopenia, a deficiency in white blood cells,
also can develop.

Waldenström’s macroglobulinemia

Chlorambucil (Leukeran), possibly in combination
with prednisone, is the typical chemotherapy choice for
WM. This treatment is effective in 57% of cases. These
drugs are taken by mouth. Prednisone is a corticosteroid that affects many body systems. It has anti-cancer
and anti-inflammatory effects and is an immune system
suppressant. Other drug combinations that are used to
treat WM include cyclophosphamide (Cytoxan), vincristine, and prednisone, with or without doxorubicin.
Fludaribine, 2-chlorodeoxyadenosine, and corticosteroids also may be used.
side effects of chemotherapy may include:

(REAL) classification system gives WM a good prognosis following treatment, with an average 5-year survival rate of 50-70%. However, many people with
WM live much longer, some without developing any
symptoms of the disease. About 16-23% of individuals
with WM die of unrelated causes.

Prevention
There is no known prevention for WM.
Resources
BOOKS



mouth sores



nausea and indigestion

Drum, David. Making the Chemotherapy Decision. 2nd ed.
Los Angeles: Lowell House, 1996.



hair loss

ORGANIZATIONS



increased appetite



nervousness



insomnia

Cure for Lymphoma Foundation. 215 Lexington Ave., New
York, NY 10016. (212) 213-9595. (800)-CFL-6848.
infocfl@cfl.org. <http://www.cfl.org/home.html>.
An advocacy organization; education and support
programs, research grants, information on clinical trials
for Hodgkin’s and non-Hodgkin’s lymphomas.
International Waldenstrom’s Macroglobulinemia
Foundation. 2300 Bee Ridge Road, Sarasota, FL 342396226. (941) 927-IWMF. <http://www.iwmf.com>.
Information, educational programs, support for patients
and families, research support.
The Leukemia and Lymphoma Society. 600 Third Ave.,
New York, NY 10016. (800) 955-4572. (914) 949-5213.
<http://www.leukemia-lymphoma.org>.
Information, support, and guidance for patients and
health care professionals.
The Lymphoma Research Foundation of America, Inc. 8800
Venice Boulevard, Suite 207, Los Angeles, CA 90034.
(310) 204-7040). <http://www.lymphoma.org>.
Research into treatments for lymphoma; educational
and emotional support programs for patients and
families.

These side effects disappear after the chemotherapy is discontinued.
The long-term management of WM usually is
accomplished through a combination of plasmapheresis and chemotherapy.
Alternative and complementary therapies
Biological therapy or immunotherapy, with the
potent, immune system protein interferon alpha, is
used to relieve the symptoms of WM. Interferon
alpha works by boosting the body’s immune response.
Interferon can cause flu-like symptoms, such as fever,
chills, and fatigue. It also can cause digestive problems
and may affect blood pressure.
The drug rituximab, an antibody that is active
against antibody-producing cells, is effective in about
30% of individuals with WM. Rituximab is a monoclonal antibody produced in the laboratory.
Monoclonal antibody treatment may cause a an allergic reaction in some people.

Prognosis
There is no cure for WM. In general, patients go
into partial or complete remission following initial treatments. However the disease is not cured and follow-up
treatment may be necessary.
The prognosis for this cancer depends on an individual’s age, general health, and genetic (hereditary)
makeup. Males, individuals over age 60, and those
with severe anemia have the lowest survival rates.
The Revised European American Lymphoma
3966

OTHER

Complementary and Alternative Therapies for
Leukemia, Lymphoma, Hodgkin’s Disease and
Myeloma. The Leukemia and Lymphoma Society.
March 27, 2001. [cited June 28, 2001]. <http://
www.leukemia-lymphoma.org>.
‘‘Macroglobulinemia of Waldenstrom.’’ WebMD.
1999. April 14, 2001. [cited June 28, 2001]. <http://
my.webmd.com/content/asset/adam_disease_
macroglobulinemia-primary>.
McKusick, Victor A. ‘‘Macroglobulinemia, Waldenstrom;
WM.’’ Online Mendelian Inheritance in Man. John
Hopkins University. December 28, 1999. [cited June28,
2001]. <http://www.ncbi.nlm.nih.gov:80/entrez/
dispomim.cgi?id=153600>.
‘‘Multiple Myeloma and Other Plasma CellNeoplasms.’’
CancerNet. National Cancer Institute. March 2001.
[cited June 28, 2001]. <http://cancernet.nci.nih.gov>.
GALE ENCYCLOPEDIA OF MEDICINE

Warts

KEY TERMS
Anemia—Any condition in which the red blood cell
count is below normal.
Antibody—Immunoglobulin produced by immune
system cells that recognizes and binds to a specific
foreign substance (antigen).

of the proteins; followed by the detection of an antigen (such as IgM), using a specific antibody.
Immunoglobulin (Ig)—Antibody such as IgM; large
protein produced by B cells that recognizes and
binds to a specific antigen.

Antigen—Foreign substance that is recognized by a
specific antibody.

Interferon alpha—Potent immune-defense protein;
used as an anti-cancer drug.
Lymphatic system—The vessels, lymph nodes, and
organs, including the bone marrow, spleen, and thymus, that produce and carry white blood cells to
fight disease.
Lymphoma—Cancer that originates in lymphatic
tissue.

Autosomal dominant—Genetic trait that is expressed
when present on only one of a pair of non-sex-linked
chromosomes.
B cell (B lymphocyte)—Type of white blood cell that
produces antibodies.
Bence-Jones protein—Light chain of an immunoglobulin that may be overproduced in Waldenstrom’s
macroglobulinemia; it is excreted in the urine.
Biopsy—Removal of a small sample of tissue for
examination under a microscope; used in the diagnosis of cancer.
Cryoglobulinemia—Condition in which protein in
the blood forms particles in the cold, blocking
blood vessels and leading to pain and numbness of
the extremities.

M protein—Monoclonal or myeloma protein; IgM
that is overproduced in Waldenstrom’s macroglobulinemia and accumulates in the blood and urine.
Monoclonal—Identical cells or proteins; cells
(clones) derived from a single, genetically-distinct
cell, or proteins produced by these cells.
Plasma cell—Type of white blood cell that produces
antibodies; derived from an antigen-specific B cell.

Hyperviscosity—Thick, viscous blood, caused by
the accumulation of large proteins, such as immunoglobulins, in the serum.

Plasmapheresis—Plasma exchange transfusion; the
separation of serum from blood cells to treat hyperviscosity of the blood.
Platelet—Cell that is involved in blood clotting.

Immunoelectrophoresis—Use of an electrical field
to separate proteins in a mixture (such as blood or
urine), on the basis of the size and electrical charge

Stem cell—Undifferentiated cell that retains the
ability to develop into any one of numerous cell
types.

Waldenstroms.com. International Waldenstrom’s
Macroglobulinemia Foundation. June 28, 2001.
<http://www.iwmf.com>.

infects the surface layer. The viruses that cause warts
are members of the human papilloma virus (HPV)
family. Warts are not cancerous but some strains of
HPV, usually not associated with warts, have been
linked with cancer formation. Warts are contagious
from person to person and from one area of the body
to another on the same person.

J. Ricker Polsdorfer, MD
Margaret Alic, PhD

Walleye see Strabismus
Description

Warts
Definition
Warts are small, benign growths caused by a viral
infection of the skin or mucous membrane. The virus
GALE ENCYCLOPEDIA OF MEDICINE

Particularly common among children, young
adults, and women, warts are a problem for 7-10%
of the population. There are close to 60 types of HPV
that cause warts, each preferring a specific skin location. For instance, some types of HPV cause warts to
grow on the skin, others cause them to grow inside the
mouth, while still others cause them to grow on the
3967

Warts

genital and rectal areas. However, most can be active
anywhere on the body. The virus enters through the
skin and produces new warts after an incubation period of one to eight months. Warts are usually skincolored and feel rough to the touch, but they also can
be dark, flat, and smooth.
Warts are passed from person to person, directly
and indirectly. Some people are continually susceptible to warts, while others are more resistant to HPV
and seldom get them. The virus takes hold more readily when the skin has been damaged in some way,
which may explain why children who bite their nails
tend to have warts located on their fingers. People who
take a medication to suppress their immune system or
are on long-term steroid use are also prone to a wart
virus infection. This same is true for patients with
AIDS.

Causes and symptoms
The more common types of warts include:


common hand warts



foot warts



flat warts



genital warts
Hand warts

Common hand warts grow around the nails, on
the fingers, and on the backs of hands. They appear
more frequently where skin is broken, such as in areas
where fingernails are bitten or hangnails picked.
Foot warts
Foot warts are called plantar warts because the
word plantar is the medical term for the sole of the
foot, the area where the wart usually appears as a single
lesion or as a cluster. Plantar warts, however, do not
stick up above the surface like common warts. The ball
of the foot, the heel and the plantar part of the toes are
the most likely locations for the warts because the skin in
those areas is subject to the most weight, pressure and
irritation, making a small break or crack more likely.
Plantar warts are familiar to all ages groups,
appearing frequently in children between the ages of
12-16. Adolescents often come into contact with a
wart virus in a locker room, swimming pool area, or
by walking barefooted on dirty surfaces. The blood
vessels feeding them are the black dots that are visible
on the wart. If left untreated, these warts can grow to
an inch or more in circumference and spread into
clusters of several warts. They are known to be very
3968

Cluster of warts on finger. (Custom Medical Stock Photo.
Reproduced by permission.)

painful at times, the pain usually compared to the
feeling of a permanent stone in the shoe particularly
if the wart is on a pressure point of the foot. People
with diabetes mellitus are prone to complications from
plantar warts related to the development of sores or
ulceration and the poor healing potential associated
with diabetes.
Flat warts
Flat warts tend to grow in great numbers and are
smaller and smoother than other warts. They can
erupt anywhere, appearing more frequently on the
legs of women, the faces of children, and on the areas
of the face that are shaved by young adult males.

Genital warts
Genital warts, also called condyloma acuminata or
venereal warts, are one of the most common causes of
sexually transmitted disease (STD) in this country.
According to the Journal of the American Medical
Association’s STD Information Center, they are contracted by sexual contact with an infected person who
carries HPV and are more contagious than other warts.
It is estimated that two-thirds of the people who have
sexual contact with a partner with genital warts will
develop the disease within three months of contact. As
a result, about one million new cases of genital warts are
diagnosed in the United States each year.
GALE ENCYCLOPEDIA OF MEDICINE

Seborrhoeic warts appearing on this patient’s back. (Custom
Medical Stock Photo. Reproduced by permission.)

Flat warts are best treated with topical retinoides
(retinoic acid) or a gel containing salicylic acid. The
acid doesn’t actually kill the wart virus, but waterlogs
the skin so that the surface layer, with the virus, peels
off. These products can take up to three months of
treatment depending on the size and depth of the wart.
Patches are also good to use. Rather than applying
drops, a small pad is placed on the wart and left for 48
hours and then replaced with a new one. The patch
usually contains a higher concentration of salicylic
acid and may irritate the surrounding skin. If this
occurs, patients should switch to a gel or stop medication for a period. To help the healing process for flat
facial warts, men should shave with an electric shaver
or temporarily grow a beard. Women with flat warts
on areas that are shaved should use other methods to
remove hair such as depilatory cream or wax.
Professional treatment

Genital warts tend to be small flat bumps or they
may be thin and tall. They are usually soft and not
scaly like other warts. In women, genital warts appear
on the genitalia, within the vagina, on the cervix, and
around the anus or within the rectum. In men, genital
warts usually appear on the tip of the penis but may
also be found on the scrotum or around the anus.
Genital warts can also develop in the mouth of a
person who has had oral sexual contact with an
infected person.

Diagnosis
Patients who notice warts in their genital area
should see a doctor. The doctor may be able to diagnose
the warts with a simple examination. If the warts are
small, the doctor may put a vinegar-like liquid on the
skin, which makes the warts turn white and easier to
see, and then use a magnifying glass to look for them.

Treatment
Home/self treatment
Many of the nonprescription wart remedies available at drug stores will remove simple warts from
hands and fingers. These medications may be lotions,
ointments, or plasters and work by chemically removing the skin that was affected by the wart virus. The
chemicals are strong, however, and should be used
GALE ENCYCLOPEDIA OF MEDICINE

Physicians should be consulted if there are no
signs of progress after a month of self treatment.
Doctors have many ways of removing warts, including
using stronger topically applied chemicals than those
available in drugstores. Some of these solutions
include podofilox, topical podophyllum, and trichloracetic acid (TCA). Some burning and discomfort for
one or more days following treatment can be expected.
Although these chemicals are effective, they may not
destroy all warts completely. A second method of
removal is freezing or cryosurgery on the wart using
liquid nitrogen. Cryotherapy is relatively inexpensive,
does not require anesthesia, and usually does not
result in scarring. Although temporarily uncomfortable, it provides an effective and safe way to deliver
freezing temperatures to a particular area on the
skin, and healing is usually quick. Physicians may
also choose to burn the wart with liquid nitrogen or
numb the skin and then scrape off the wart. Another
removal process is electrocautery (electric burning),
destroying the wart by burning it with an electric
needle. Laser surgery is also becoming a more common option for removing warts.
Genital warts are the most difficult to treat. They
can be removed, but the viral infection itself cannot be
cured. Often, because the warts are so small, more
than one treatment may be needed. The virus continues to live in the deeper skin, which is why warts
often return after they have been removed. Strong
3969

Warts

with care since they can remove healthy as well as
infected skin. These solutions should be avoided by
diabetics and those with cardiovascular or other circulatory disorders whose skin may be insensitive and
not appreciate irritation.

Warts



Place a crushed or sliced garlic clove over the wart for
seven consecutive nights while sleeping.



Soak the wart in water, put cross-hatches over it with
a sterile needle, and apply drops of thuja (Thuja
occidentalis) tincture onto the wart. Repeat the
cross-hatching and tincture application until the
wart is saturated with the tincture. Repeat several
times each day for one to two weeks. (A tincture is an
herbal extract made with alcohol.)



Tape a piece of banana peel, latex side down, over the
wart and leave it on overnight. Repeat nightly for
one to two weeks.

KEY TERMS
Condyloma acuminata—Another term for genital
warts.
Cryotherapy—Freezing with liquid nitrogen for
removal.
Endometritis—Inflammation of the endometrium
or mucous membrane of the uterus.
Epidermis—The outer layer of human skin.
Human papilloma virus (HPV)—A family of viruses
that causes hand warts, foot warts, flat warts and
genital warts.
Retinoic acid—Vitamin A1 acid which is used topically to treat acne.
Salicylic acid—An agent prescribed in the treatment of hyperkeratotic skin conditions and fungal
infections.

chemicals may be applied as well as surgical excision
with or without electrocautery. This therapy requires a
small operative procedure and a local anesthetic.
Laser therapy, although more expensive, is often
used for treating venereal warts that are more extensive. The use of lasers which vaporize the lesion can
theoretically transmit the HPV. It is not at all clear,
however, if this occurs.
There is no one recommended method for eliminating plantar warts. If detected early, cryotherapy is
usually enough. However, they can be very resilient,
requiring treatment over several months. Treatment
ranges from the conservative approach of applying
chemical solutions to the more aggressive option of
surgery. Patients with diabetes or vascular disease are
usually treated with the more conservative methods.

Alternative treatment
There are a variety of alternative approaches to
the treatment of warts. The suggestions described
below apply to common warts and plantar warts, not
to genital or cervical warts. Since genital and cervial
warts are transmitted sexually, they should be treated
by a physician
For the treatment of common or plantar warts,
alternative practitioners may recommend these
remedies.


Apply a paste made of vitamin C powder to the wart
for one to two weeks.

3970

Because warts are caused by a virus, general
immune system support can be effective in helping to
keep warts from coming back after treatment or to
keep them from multiplying or growing. Eating a well
balanced diet high in sources of vitamins A, C, and E
can help strengthen the immune system. Avoiding
stress, which is believed to compromise the immune
system, is also helpful.

Prognosis
Even though genital warts may be removed, the
virus itself continues to live. The HPV can cause tissue
changes in the cervix of women with cervical infection.
The general recommendation for women who have a
history of genital warts is to see their doctors every six
months for Pap smears to monitor any changes that
may occur.
For plantar warts, the treatment goal is to destroy
the wart and its virus without causing much damage to
healthy skin. It is not unusual for treatment to cause
pain until the foot heals because of the weight put on
the foot.

Prevention
Genital warts can be prevented by using condoms
and avoiding unprotected sex. Barrier protection will
not, however, prevent the spread of wart-causing HPV
to uncovered areas such as the pubis and upper thighs.
Plantar warts can be prevented by wearing shoes,
changing shoes daily, keeping feet clean and dry, and
not ignoring skin growths and changes in the skin.
Resources
ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014.
(847) 330-0230. Fax: (847) 330-0050. <http://
www.aad.org>.
GALE ENCYCLOPEDIA OF MEDICINE

Ruthan Brodsky

Water pills see Diuretics
Water therapy see Hydrotherapy
Waterhouse-Friderichsen syndrome see
Meningococcemia
Weber test see Hearing tests with a tuning fork

Wechsler intelligence test
Definition
The Wechsler Intelligence Scales are a series of
standardized tests used to evaluate cognitive abilities and intellectual abilities in children and
adults.

Purpose
The Wechsler Intelligence Scales for Children
(regular, revised, and third edition) and Wechsler
Preschool and Primary Scale of Intelligence are used
as tools in school placement, in determining the presence of a learning disability or a developmental
delay, in identifying giftedness, and in tracking intellectual development.
The Wechsler Adult Intelligence Scales (regular
and revised) are used to determine vocational ability, to assess adult intellectual ability in the classroom, and to determine organic deficits. Both
adult and children’s Wechsler scales are often
included in neuropsychological testing to assess
the brain function of individuals with neurological
impairments.

Precautions
Intelligence testing requires a clinically trained
examiner. The Wechsler scales should be
GALE ENCYCLOPEDIA OF MEDICINE

administered, scored, and interpreted by a trained
professional, preferably a psychologist or psychiatrist.

Description
All of the Wechsler scales are divided into six
verbal and five performance subtests. The complete
test takes 60-90 minutes to administer. Verbal and
Performance IQs are scored based on the results of
the testing, and then a composite Full Scale IQ score is
computed. Although earlier editions of some of the
Wechsler Scales are still available, the latest revisions
are described below:
Wechsler Adult Intelligence Scale-Revised
(WAIS-R)
The WAIS-R, the 1981 revision of the original
Wechsler Adult Intelligence Scale, is designed for
adults, age 16-74. The 11 subtests of the WAIS-R
include information, digit span, vocabulary, arithmetic, comprehension, similarities, picture completion, picture arrangement, block design, object
assembly, and digit symbol. An example of questions
on the subtest of similarities might be: ‘‘Describe how
the following pair of words are alike or the same—
hamburger and pizza.’’ A correct response would be
‘‘Both are things to eat.’’
Wechsler Intelligence Scale for Children,
Third Edition (WISC-III)
The WISC-III subtests includes many of the same
categories of subtests as the WAIS-R. In addition,
there are two optional performance subtests: symbol
search and mazes.
Wechsler Preschool and Primary Scale
of Intelligence (WPPSI)
The WPPSI is designed for children age 4-6½
years. The test is divided into six verbal and five performance subtests. The eleven subtests are presented
in the following order: information, animal house and
animal house retest, vocabulary, picture completion,
arithmetic, mazes, geometric design, similarities, block
design, comprehension, and sentences.
The 1997 Medicare reimbursement rate for
psychological and neuropsychological testing, including intelligence testing, is $58.35 an hour. Billing time
typically includes test administration, scoring and
interpretation, and reporting. Many insurance plans
cover all or a portion of diagnostic psychological
testing.
3971

Wechsler intelligence test

American Academy of Family Physicians. 8880 Ward
Parkway, Kansas City, MO 64114. (816) 333-9700.
<http://www.aafp.org>.
American Podiatric Medical Association. 9312 Old
Georgetown Road, Bethesda, MD 20814-1698. (301)
571-9200. <http://www.apma.org>.
Dermatology College of Medicine. The University of Iowa,
200 Hawkins Dr., Iowa City, IO 52242. (319) 356-2274.
<http://tray.dermatology.uiowa.edu>.

Wegener’s granulomatosis

KEY TERMS
Norms—Normative or mean score for a particular
age group.
Representative sample—A random sample of people that adequately represents the test-taking population in age, gender, race, and socioeconomic
standing.
Standard deviation—A measure of the distribution of scores around the average (mean). In a
normal distribution, two standard deviations
above and below the mean includes about 95%
of all samples.
Standardization—The process of determining
established norms and procedures for a test to
act as a standard reference point for future test
results.

Normal results
The Wechsler Intelligence Scales are standardized
tests, meaning that as part of the test design, they were
administered to a large representative sample of the
target population, and norms were determined from
the results. The scales have a mean, or average, standard score of 100 and a standard deviation of 15. The
standard deviation indicates how far above or below
the norm the subject’s score is. For example, a ten-yearold is assessed with the WISC-III scale and achieves a
full-scale IQ score of 85. The mean score of 100 is the
average level at which all 10-year-olds in the representative sample performed. This child’s score would be
one standard deviation below that norm.
While the full-scale IQ scores provide a reference
point for evaluation, they are only an average of a
variety of skill areas. A trained psychologist will evaluate and interpret an individual’s performance on the
scale’s subtests to discover their strengths and weaknesses and offer recommendations based upon these
findings.
Resources
ORGANIZATIONS

American Psychological Association (APA). 750 First St.
NE, Washington, DC 20002-4242. (202) 336-5700.
<ttp://www.apa.org>.
Catholic University of America. Washington, DC 20064.
(800) 464-3742. <http://www.ericae.net>.

Paula Anne Ford-Martin
3972

Wegener’s granulomatosis
Definition
Wegener’s granulomatosis is a very rare disease
that affects many different organs and systems of
the body. It mainly attacks the respiratory system
(sinuses, nose, windpipe, and the lungs) and the
kidneys. One of the main features of the disease is an
inflammation of the blood vessels (vasculitis). The
inflammation narrows the blood vessels and reduces
the blood flow to the affected organs. This destroys
tissues and damages vital organs.

Description
Wegener’s granulomatosis (WG) is not a contagious disease, and there is no evidence to suggest that it
is hereditary either. It is a very rare disease, affecting
only 1 in every 30,000-50,000 people. About 500 new
cases are diagnosed each year. The disease can occur at
any age, however, it mostly affects individuals in their
30s and 40s. It affects males and females equally.
Ninety seven percent of all patients are Caucasian,
2% are Black and 1% are of another race.

Causes and symptoms
No viral, bacterial, or other causative agent has
yet been identified for WG. It is thought to be an
autoimmune disease, meaning that the body’s immune
system attacks ‘‘itself,’’ that is, the body’s own tissues.
Whenever there is an infection in the body, proteins called antibodies, which are capable of attacking
the infectious agent, are formed in the blood. In WG,
the antibodies that are formed are directed against the
white blood cells of the immune system. They are
therefore called ‘‘auto-antibodies’’ (antibodies against
one’s own body cells). These auto-antibodies bind to
the blood cells and forms clumps known as immune
complexes. The complexes accumulate in the tissues
and the blood vessels, leading to a tumor-like (granulomatous) inflammation of the blood vessels. This
slows down the blood flow to the different organs
and tissues, causing damage and resulting in the
many symptoms of WG.
The symptoms of WG, and the severity of
the symptoms, vary from patient to patient. One of
the most common features is a chronic runny nose
and other cold-like symptoms that do not respond to
standard treatment. The cold symptoms gradually worsen and could lead to sinusitis (inflammation of the
sinuses), middle ear infection (otitis media), cough,
GALE ENCYCLOPEDIA OF MEDICINE

Kidney (renal) disease is the most serious development of WG. Patients who do not have renal disease
are said to have ‘‘Limited Wegener’s.’’

Diagnosis
Early diagnosis is critical for the most effective
treatment of the disease. However, there are no specific laboratory tests for WG. Blood tests are used
to rule out other causes of the symptoms and to determine which organs are affected. The blood tests often
show anemia (low red cell count) and high white blood
cell counts. If the kidneys are involved, red blood cells
are seen in the urine when viewed under a microscope.
Also, blood tests aimed at measuring kidney function
may show abnormalities.
Chest x rays are used to determine if the lungs are
involved. Computed tomography scans (CT scans) of
sinuses and lungs, and kidney biopsy, are also important tools used in diagnosing WG.
A specific type of antibody called anti-neutrophil
cytoplasmic antibody (ANCA) is seen in the blood of
about 90% of the patients with WG. The ANCA are a
group of antibodies directed against the individual’s
own white blood cells (namely, the neutrophils). These
anti-neutrophil cytoplasmic antibodies are also found
in other inflammatory conditions and diseases (such as
HIV infection). Though the ANCA test is useful, it
cannot be used by itself to make a diagnosis of WG.
However, the amount of ANCA in the blood can be
measured and correlates well with the progression of
the disease. When there is a relapse or a flare-up, the
ANCA levels go up. Levels decrease when the disease
is controlled by appropriate treatment.
Since there are no definitive laboratory tests for
WG, and the initial symptoms of the disease are not
very specific, it takes five-15 months, on an average, to
make a diagnosis of WG.

Treatment
Cyclophosphamide (Cytoxan) which is an anticancer drug, and corticosteroids, such as prednisone,
are used to treat WG. These are powerful drugs that
suppress the immune system. However, they are also
very toxic and can have serious side effects. The
patient has to be watched carefully by the doctors
and the dosage of the drugs has to be adjusted, if
needed.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Auto-antibodies—An antibody that is produced in,
and reacts with, an antigen in the same person or
animal.
Autoimmune disease—Any disease which causes
tissue injury due to an immunological reaction of
antibodies against the patient’s own tissues.
Granulomatous—Resembling a tumor made of
granular material.
Immune complexes—Clusters or aggregates of
antigen and antibody bound together.
Vasculitis—Inflammation of the walls of the blood
vessels.

Since the patient’s immune system is suppressed
while on these drugs, he or she is at an increased risk
for contracting infections. Vaccinations for flu and
pneumonia are recommended.

Prognosis
In the past, approximately 80% of the patients
with untreated WG died within a year of contracting
the disease and 90% died within two years. Today,
however, the prognosis has been dramatically
improved. With appropriate treatment, patients can
survive for much longer periods and lead relatively
normal lives.
Approximately 50% of the patients with WG will
have a relapse of the disease. This generally happens
within two years of stopping the medication, but can
occur at any point either during treatment or after
stopping treatment. Therefore, it is extremely important that patients continue to see their doctors regularly
even after stopping the medications.

Prevention
At present, there are no preventive measures
known for Wegener’s granulomatosis.
Resources
ORGANIZATIONS

National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.
Wegener’s Foundation, Inc. 3705 South George Mason
Drive, Suite 1813 South, Falls Church, VA 22041. (703)
931-5852.
3973

Wegener’s granulomatosis

coughing of blood, and inflammation of the lung
(pleuritis and pneumonia). Other symptoms include
fever, fatigue, loss of appetite, weight loss, joint pain,
night sweats, change in urine color, and weakness.

Weight loss drugs

Wegener’s Granulomatosis Support Group, Inc. P.O. Box
28660, Kansas City, MO 64188-8660. (800) 277-9474.
<http://www.wgsg.org/wgsg>.

Lata Cherath, PhD

BMI charts are widely available; however, an
approximate BMI can be calculated by the following
these steps:


multiplying body weight in pounds by 703



dividing the result by height in inches



dividing the result by height in inches again

With the exception of very muscular people, BMI
is a measure of health:

Weight loss drugs
Definition
Weight loss drugs are medications that may help
an obese person lose weight in combination with a
low-calorie diet and physical activity.

Purpose
More than 60% of American adults are overweight or obese. Since the 1980s the number of overweight people has increased steadily and the number
of obese people has almost doubled. Excess weight
and physical inactivity account for more than
300,000 premature deaths in the United States each
year, second only to smoking-related deaths.
Risks from Obesity
Overweight and obese people are at higher risk for
developing the following problems:



18.5–24.9: healthy



25–29.9: overweight



30 or above: obese

Generally the higher the BMI the higher the risk
of health problems; however, excess abdominal fat is a
separate health risk. Men with waists of more than 40
in (102 cm) and women with waists of more than 35 in
(89 cm) are at greater risk for health problems.
Prescription weight loss drugs are approved for
use only by people with BMIs of 30 or above or those
with BMIs of 27 and above who have other risk factors, including the following:


high blood pressure



type 2 diabetes



dyslipidemia (abnormal amounts of fat in the blood)



sleep apnea

Even short-term weight loss in some obese people
has been found to reduce the following:



sleep apnea (interrupted breathing while asleep)



blood pressure



osteoarthritis (wearing away of the joints)



blood cholesterol



high blood pressure



triglyerides (fats)



heart disease



insulin resistance (the inability to utilize blood sugar)



stroke



diabetes



gallbladder disease



gout (joint pain caused by excess uric acid)



many common types of cancer
Body mass index (BMI)

An overweight person has an excess of body
weight but not necessarily an excess of body fat.
Obesity refers to an excessively high proportion of
body fat. The BMI is used to determine whether a
person is overweight or obese. It defines body weight
relative to height and, for most adults, correlates with
total body fat.
3974

Overweight or obese patients who have not lost an
average of 1 lb (0.5 kg) per week after at least six
months on a balanced low-calorie diet, including
increased exercise and behavior therapy, may be considered candidates for weight loss drugs.

Description
Weight loss medications are prescribed only as a
component of a weight loss program that includes a
healthy low-calorie diet and regular physical activity.
On average, people on prescription weight loss drugs
lose about 5–10% of their original weight. They may
lose in the range of 4.4–22 lb (2–10 kg) above what
they might have lost following a diet and exercise
program alone. Patients who lose weight initially on
a drug tend to continue to respond. However, those
GALE ENCYCLOPEDIA OF MEDICINE

Most weight loss occurs within the first six months
of drug use, after which the weight levels off or
increases. The majority of patients regain the lost
weight after discontinuing the medication. Thus
short-term use of weight loss drugs may not be beneficial. However, long-term use of weight loss drugs
may help maintain the lower weight. Since obesity is
a chronic disorder, treatment must be continued for
years or for life. However, as of 2005, sibutramine
(Merida) and orlistat (Xenical) were the only weight
loss drugs approved by the U. S. Food and Drug
Administration (FDA) for use for more than a few
weeks.
Appetite suppressants (anorexiants)
Most FDA-approved weight loss drugs suppress
appetite by affecting one or more neurotransmitters in
the brain that control appetite and mood. Various
appetite suppressants increase the secretion of dopamine, norepinephrine, or serotonin or inhibit the reuptake of these neurotransmitters into the nerve cell.
Some drugs affect more than one neurotransmitter.
These drugs may cause a person to feel less hungry
or more satiated.
SIBUTRAMINE. Sibutramine

was approved by
the FDA in 1997 for long-term use. It reduces appetite
by inhibiting the reuptake of norepinephrine, dopamine, and serotonin. One study found that patients
taking sibutramine lost an average of 7–10 lb (3—5 kg)
more over one year than those on a low-calorie diet
alone.
AMPHETAMINES OR SYMPATHIMIMETIC DRUGS.

Some amphetamines are FDA-approved for very
short-term weight loss. Although most of these drugs
do not cause weight loss over more than a few weeks,
phentermine continues to be one of the two most
commonly prescribed weight loss medications—
along with subitramine—in the United States.
Some amphetamine-type weight loss drugs, including methamphetamine (Desoxyn), were approved by the
FDA in the mid-1990s based on very little data. Other
FDA-approved weight loss drugs for short-term use
include:


benzphetamine (Didrex)



diethylpropion (Tenuate, Tenuate Dospan, Tepanil
Ten-Tab), approved in 1959

GALE ENCYCLOPEDIA OF MEDICINE



mazindol (Mazanor, Sanorex)



phendimetrazine (Adipost, Bontril PDM, Bontril
Slow-Release, Melfiat, Obezine, Phendiet, Phendiet105, PT 105, Plegine, Prelu-2, X-Trozine,), approved
in 1982



phentermine (Adipex-P, Fastin, Ionamin, Obenix,
Oby-trim, Phentercot, Phentride, Pro-Fast, Teramine,
Zantryl), approved in 1959
Lipase inhibitors

In 1999 the FDA approved orlistat (the first of a
new class of anti-obesity drugs called lipase inhibitors)
for long-term use. Orlistat inhibits the pancreatic
enzyme lipase that breaks down dietary fat, which in
turn decreases the body’s absorption of dietary fat by
as much as 30%. The undigested fat is excreted in the
stool.
Orlistat is prescribed for overweight or obese
patients who also have high cholesterol, diabetes,
high blood pressure, or heart disease
Off-label use
Physicians sometimes prescribe drugs for weight
loss that are not FDA-approved for that purpose—
so-called off-label use. The use of weight loss medications—other than sibutramine and orlistat—for more
than a few weeks is also considered off-label use.
Off-label weight loss drugs include:


antidepressants such as bupropion



the anticonvulsant drugs topiramate and zonisamide



the diabetes medication metformin

Antidepressants may result in moderate weight
loss for up to six months after which the weight usually
is regained. Metformin appears to reduce hunger and
food intake and may promote small weight loss in the
obese and those with type 2 diabetes.
Drugs withdrawn from the market
Although effective for long-term weight loss, fenfluramine (Pondimin and others), dexfenfluramine
(Redux), and a fenfluramine/phentermine combination (fen/phen) were withdrawn from the market in
1997 after it was found that they caused potentially
fatal complications.
In February of 2004 the FDA prohibited the sale
of dietary supplements containing ephedrine alkaloids, including ephedra, Ma huang, Sida cordifolia,
and pinellia, because of potential complications. These
supplements were aggressively marketed for weight
3975

Weight loss drugs

who fail to lose 4 lb (2 kg) within the first month on a
weight loss medication are unlikely to respond to that
particular drug even at an increased dosage. Over-thecounter weight loss drugs have been found to be ineffective, unsafe, or both.

Weight loss drugs

control, as well as for energy and sports performance.
Although they may effect modest short-term weight
loss, these drugs raise blood pressure, stress the circulatory system, and have been linked to heart attack
and stroke.

Recommended dosage
Dosages of appetite suppressants vary with the
individual and a full dose may be more than necessary
for some people. A low dose of subitramine often is
prescribed for at least the first four weeks. Once-a-day
appetite suppressors should be taken 10–14 hours
before bedtime. When taking more than one dose per
day, the last dose should be 4–6 hours before bedtime.
Long-acting capsules or tablets should be swallowed
whole, rather then chewed or cut up. Missed doses
should be skipped.
The average doses of appetite suppressants are:


sibutramin: a 10-mg capsule once a day, usually in
the morning; a maximum of 15 mg per day



benzphetamine: 25 to 50-mg tablets once a day in
midmorning or mid-afternoon



diethylpropion: 25-mg tablets, three times per day,
one hour before meals; 75-mg extended-release
tablet, once a day in midmorning



mazindol: 1-mg tablet once a day, taken with food



phendimetrazine: 17.5–35-mg tablets, two to three
times per day, one hour before meals; 105-mg
extended-release capsules, 30 to 60 minutes before
the morning meal



phentermine: 15–37.5-mg capsule or tablet, once a
day, before breakfast or one to two hours after or
smaller doses 30 minutes before meals; 15–30-mg
oral resin capsule, once-per-day, before breakfast

The usual dose of orlistat is a 120-mg capsule
taken three times a day, up to one hour after each
main meal that contains fat. The meal should contain
no more than 30% calories from fat. Orlistat should
not be taken if a meal is missed, the meal does not
contain fat, or it is more than one hour past the meal.

of 2005. Orlistat is approved for use in those aged 12
and above. No other weight loss drug is approved for
use in children under age 16.
After beginning a weight loss drug, patients
should return for follow-ups in two to four weeks,
monthly for three months, and then every three
months for the first year, to monitor weight, blood
pressure, pulse, and side effects, and have laboratory
testing.
Appetite suppressants
Appetite suppressants should not be taken within
14 days of taking a monoamine oxidase (MAO) inhibitor; extremely high blood pressure and seizures may
develop suddenly. Taking subitramine along with a
drug that has MAO-inhibitor activity can cause a
life-threatening condition called serotonin syndrome.
Sibutramine should not be used by people with the
following problems:


poorly-controlled high blood pressure



irregular heartbeat (arrhythmia)



a history of stroke



heart disease



congestive heart failure

Appetite suppressants, including sibutramine, can
be habit-forming. In late 2004 Meridia was singled out
by critics as a drug that is only minimally effective and
has been associated with several deaths.
Amphetamine-type weight loss drugs should not
be use by anyone with the following problems:


high blood pressure



heart disease



an overactive thyroid gland



glaucoma

Amphetamine-type weight loss drugs can test
positive on urine screenings for amphetamines. These
drugs have a high potential for abuse and addiction.
Orlistat

Precautions
With the exception of orlistat, all prescription
weight loss medications are controlled substances.
Very few studies have evaluated for their safety or
effectiveness for periods of more than six months to
two years. The use of any combination of weight loss
drugs is not recommended. The risks of using appetitesuppressing drugs during pregnancy are unknown as
3976

Orlistat may decrease the absorption of fat-soluble
vitamins and beta-carotene. Therefore, a daily multivitamin supplement, including vitamins A, E, K, and betacarotene, should be taken at least two hours before or
after orlistat or at bedtime. Foods containing more than
30% fat should be avoided while a person is using orlistat. Gallbladder problems may become worse with
orlistat.
GALE ENCYCLOPEDIA OF MEDICINE

Various conditions may affect the choice of a
weight loss drug, including the following:



constipation



nausea or vomiting

Weight loss drugs

Other precautions



drowsiness



pregnancy or breastfeeding



insomnia



a history of drug or alcohol abuse or dependence



irritability



a history of eating disorders



anxiety



a history of depression or manic-depressive disorder



dizziness, lightheadedness, confusion



a family history of mental illness



poor coordination



the use of MAO inhibitors or other antidepressants



migraine headaches requiring medication



glaucoma



diabetes mellitus



epilepsy

Less common side effects of appetite suppressants
include:



thyroid disease



fast or irregular heart beat



kidney problems



skin rash or hives



gallstones



fever



liver disease



sore throat



problems absorbing food (malabsorption syndrome)



sweating



high blood pressure



uncontrollable trembling or shaking



heart disease, a heart condition such as arrhythmia,
blood vessel disease



diarrhea



unusual bruising or bleeding

future surgery that will require general anesthesia



depression



Some dietary supplements are marketed as weight
loss products. They are not reviewed by the FDA and
are not necessarily safe. They may interact with other
drugs and may be dangerous for people with certain
medical conditions. Herbal medications have unpredictable amounts of active ingredients and unpredictable and potentially harmful side effects.

Side effects
Many overweight people are generally healthy
and the side effects of weight loss drugs may far outweigh the benefits. Side effects may be reduced by
starting at the lowest effective dose, although any
drug can cause an allergic reaction in any individual.
Appetite suppressants
Side effects of sibutramine and other appetite
suppressants may include:

Dry mouth can be relieved with sugarless candy or
gum, ice, or a saliva substitute. However, dry mouth
lasting more than two weeks can increase the risk of
serious dental disease.

Although sibutramine side effects usually are mild
and may improve with continued use, additional side
effects may include:


increased thirst



changes in sense of taste



heartburn



stuffy or runny nose



skin burning, itching, prickling, or tingling



back pain



painful menstruation



weakness



swelling in various parts of the body

Fast heart rate can be a symptom of sibutramine
overdose. Other rare serious complications from subitramine include:


chest pain



difficulty speaking, swallowing, or breathing



increased blood pressure



muscle stiffness



dry mouth



uncoordinated or abnormal movement



headache



fainting



abdominal cramps or pain



rapid mood shifts

GALE ENCYCLOPEDIA OF MEDICINE

3977

Weight loss drugs



enlarged pupils, eye pain, vision changes



tooth or gum problems



confusion



chest tightness



seizures



wheezing



anxiety

Other side effects of amphetamines can include:


a false sense of well-being



an unpleasant taste

Orlistat side effects requiring immediate medical
attention include:



decreased alertness



itching, rash, or hives



restlessness



fever



uncontrollable activity or excitement



frequent, difficult, or painful urination



hallucinations



bloody or cloudy urine



increased need to urinate



swelling of body parts



difficult or painful urination



chest pain



numbness, particularly on one side of the face or body



difficulty breathing



blurred vision



earache or hearing changes



changes in libido or decreased sexual function

Higher dosages, more frequent doses, or longerterm use of amphetamines can lead to physical dependence or overdose, with symptoms that include:

Orlistat side effects can be worsened by eating
meals with at least 30% of total calories from fat.
Side effects usually disappear within two to three
days after discontinuing the drug.



skin disease



severe insomnia



excessive excitability or irritability



panic

Appetite-suppressants can interact negatively
with numerous other drugs, including the following:



violent urges



other appetite suppressants and amphetamines



personality changes



caffeine



severe mental illness



cold and allergy medicines



high or low blood pressure



asthma medications



seizures



selective serotonin reuptake inhibitors (SSRIs)



coma


tricyclic antidepressants



medications used during surgical, dental, or emergency procedures



cocaine and other street drugs

Symptoms of withdrawal may be lessened or prevented by gradually reducing the dosage.
Orlistat
Orlistat side effects usually are mild and can improve
with continued use; they may include the following:


intestinal discomfort or cramping



flatulence



Interactions

In addition to the above, subitramine is known to
interact with numerous other drugs, including the
following:


pain relievers and muscle relaxants

frequent, urgent need to defecate



sulfa antibiotics



inability to control bowel movements and leakage



antifungal medications



oily diarrhea



sedatives, sleeping pills, tranquilizers



flu- or cold-like symptoms



high-blood-pressure medications



irregular menstrual periods



migraine-headache medications



medications for nausea, anxiety, mental illness,
seizures



blood thinners such as warfarin (Coumadin)

Less common side effects of orlistate include:


rectal pain



back pain

3978

GALE ENCYCLOPEDIA OF MEDICINE

Amphetamines—Sympathomimetic amines; sometimes called speed; synthetic chemicals that stimulate the central nervous system.
Body mass index (BMI)—The correlation of body
weight with height; usually correlates with total
body fat.
Dopamine—A neurotransmitter and precursor of
norepinephrine; found in high concentrations in
the brain.
Ephedrine—A sympathomimetic amine from
plants of the genus Ephedra or chemically synthesized; an asthma medication that previously was
used in weight loss drugs.
Lipase—A fat-splitting enzyme found in pancreatic
juice, blood, and many tissues.
Neurotransmitter—A substance that helps transmit
impulses between two nerve cells or a nerve and
muscle.
Norepinephrine—A hormone that constricts blood
vessels.
Orlistat—A drug that inhibits lipase.
Phentermine—An amphetamine prescribed for
appetite suppression.
Serotonin—5-Hydroxytryptamine; a chemical in
various parts of the body that stimulates smooth
muscle contraction, constricts blood vessels, and
inhibits stomach secretions.
Sibutramine—An appetite-suppressing drug that
may increase the activity of norepinephrine and
serotonin in the brain.



chemotherapies
Orlistat may interact with the following:



other weight loss medications



diabetes medications, including insulin



blood thinners



herbal products



cyclosporine

Resources
BOOKS

Mitchell, Deborah R., and David Charles Dodson. The Diet
Pill Book: A Consumer’s Guide to Prescription and Overthe-Counter Weight-Loss Pills and Supplements.
New York: St. Martin’s Press, 2002.
GALE ENCYCLOPEDIA OF MEDICINE

Fuhrmans, Vanessa. ‘‘Medicare Mulls Coverage Shift on
Obesity; As Panel Takes Up Issue of Surgery for Weight
Loss, Private Carriers Begin Covering More
Treatments.’’ Wall Street Journal November 3, 2004: D1.
Jarvis, Lisa. ‘‘Sanofi-Aventis Drug Poised to Crack Open
Obesity Market.’’ Chemical Market Reporter 266, no.
17 (November 15, 2004): 10.
‘‘Weight Loss: Drugs Aid Weight Loss Among Type 2
Diabetes Patients.’’ Health & Medicine Week March 14,
2005: 1572.
ORGANIZATIONS

American Obesity Association. 1250 24th Street, NW, Suite
300, Washington, DC 20037. (800)986-2373. <http://
www.obesity.org>.
Food and Drug Administration. U.S. Department of Health
and Human Services, Public Health Service, 5600
Fishers Lane, Rockville, MD 20857. <http://
www.fda.gov>.
Weight-control Information Network (WIN). National
Institute of Diabetes and Digestive and Kidney
Diseases. 1 Win Way, Bethesda, MD 20892-3665.
(877)946-4627. <http://www.niddk.nih.gov/health/
nutrit/win.htm>.
OTHER

Bren, Linda. ‘‘Losing Weight: More than Counting
Calories.’’ FDA Consumer. Federal Citizen Information
Center. April 2002 [cited March 6, 2005]. <http://
www.pueblo.gsa.gov/cic_text/health/count-cal/
loseweight.html>.
‘‘FDA Issues Regulation Prohibiting Sale of Dietary
Supplements Containing Ephedrine Alkaloids and
Reiterates Its Advice that Consumers Stop Using These
Products.’’ FDA News. U.S. Food and Drug
Administration. February 6, 2004 [cited March 6, 2005].
<http://www.cfsan.fda.gov/~1rd/fpephedt.html>.
‘‘Prescription Medications for the Treatment of Obesity.’’
Weight-control Information Network. November 2004
[cited March 12, 2005]. <http://www.niddk.nih.gov/
publications/prescription.htm>.
‘‘Treatment Guideline.’’ Guidelines on Overweight and
Obesity: Electronic Textbook. National Heart, Lung,
and Blood Institute. [Cited March 20, 2005]. <http://
www.nhlbi.nih.gov/guidelines/obesity/e_txtbk/txgd/
4325.htm>.

Margaret Alic, Ph.D.

Weil’s disease see Leptospirosis
Wermer’s syndrome see Multiple endocrine
neoplasia syndromes
Wernicke-Korsakoff disease see Alcoholrelated neurologic disease
3979

Weight loss drugs

PERIODICALS

KEY TERMS

West Nile virus

Western equine encephalitis see Arbovirus
encephalitis
Western herbalism see Herbalism, western

West Nile virus
Definition
West Nile virus is a mosquito-borne viral illness
that can manifest with varying seriousness, ranging
from no symptoms or mild flu-like symptoms to
brain damage and death.

Description
West Nile virus (WNV) is a mosquito-borne flavivirus belonging to the Japanese encephalitis serocomplex, which includes St. Louis encephalitis,
Murray Valley encephalitis, and Kunjin virus.
Zoonotically maintained, infections occur generally
between late summer and early fall in temperate
areas, and throughout the year in southern climates.
Although typical manifestation of WNV is asymptomatical, the virus can cross the blood-brain barrier
and cause severe illness, paralysis, and even death in
humans and animals.
The WNV was originally isolated in a feverish
woman living in the West Nile District of Uganda
during 1937. The virus was ecologically characterized
in Egypt during the 1950s and later linked to severe
human meningoencephalitis in elderly patients during
a 1957 outbreak in Israel. Since 1937, subsequent outbreaks of WNV have been reported in Africa, Asia,
Australia, Oceania, Western Europe, and the Middle
East.
In the summer of 1999, the first North American
cases of WNV occurred in the New York City area. It
is still unknown how the WNV reached the continental
United States, but it is suspected that the transport of
infected birds or the international travel of infected
humans may have been to blame. After its arrival in
the New Work area,, the virus spread rapidly across
the United States, as well as northward into Canada
and southward into Mexico. In 2002, a severe outbreak of WNV in the United States killed 284 people
and caused 2,944 cases of severe brain damage. During
another outbreak a year, 9,858 cases of WNV infection were reported, of which over 2,900 were severe in
nature and 262 of which resulted in fatality. As of
January 2005, the CDC ArboNET has recorded
3980

avian or animal WNV infections in every state except
Alaska, Hawaii, and Washington. Additionally, the
CDC ArboNET recorded human WNV infections in
every state except Alaska, Delaware, Hawaii,
Massachusetts, New Hampshire, Rhode Island,
Vermont, Washington, and West Virginia. Experts
believe that WNV is now firmly established in the
Western Hemisphere.
Life Cycle and Transmission
Like most flaviviruses, the WNV is maintained in
a natural host-vector-host cycle, where the primary
vector is the mosquito. The zoonotic cycle begins
with a reservoir host, which is most commonly of
avian origin. When a mosquito feeds on the infected
bird, the virus is passed to the insect along with the
blood meal. The virus then multiplies rapidly within
the mosquito’s body and salivary glands over the next
few days. When the insect feeds on another animal or
human, the virus can be transmitted through the bite
and cause serious illness.
Most mosquitoes can become infected with the
WNV. However, female mosquitoes of the Culex
pipiens species are of particular concern, as they live
in suburban and urban areas, can survive through the
winter, prefer to feed on birds, and frequently bite
humans. The Culex pipiens, also known as the house
mosquito, is also the most common vector for WNV
transmission. Culex restuan, Culex quinquefasciatus,
Aedes Albopictus, and Aedes Vexans are also common
carriers of the WNV.
Common food sources for mosquitoes, birds
represent the primary WNV reservoir species.
American crows, in particular, are extremely susceptible to WNV, and have become the virus’ primary
host population. Indeed, an unusual crow die-off can
be used as an excellent indicator for the regional presence of the WNV. The virus has also been identified
in more than 250 bird species in the United States,
including blue jays, ravens, magpies, sparrows, and
starlings. Many in the scientific community believe
that the rapid spread of WNV in North America
may be due in part to the migratory nature of birds.
Infected birds carry the virus with them as they travel
in summer and winter, thus acting as reservoirs in their
new nesting sites.
Most vertebrates, such as alligators, bats, chipmunks, skunks, squirrels, and rabbits, can also be
infected with WNV. Horses, in particular, are commonly infected with WNV. Like humans, the majority
of horses suffer either no or mild symptoms, but severe
illness and death can and does occur. There are
GALE ENCYCLOPEDIA OF MEDICINE

There is no evidence of WNV transmission from
person-to-person through touch, kissing, or other contact. However, there is evidence of WNV transplacental (mother-to-child) transmission, as well as viral
transmission through breastfeeding. As such, pregnant mothers should be aware of the presence of
WNV in their area and take appropriate precautions.
The transmission of WNV has also been evidenced in
blood-transfusions and organ transplants; although
the current blood supply is now tested for the presence
of the WNV. People that are immunocompromised
(from disease or chemotherapy, for example) and people aged 50 and older represent the highest risk group
for serious WNV infection.

Causes and symptoms
The exact mechanism of WNV-caused illnesses
remains unclear. However, it is suspected that the
virus enters the host’s blood stream and multiples. It
can then develop to the point where it crosses the blood
brain-barrier, which separates the blood from the central nervous system. When this occurs, the virus can
infect the brain, spinal cord, and other vital systems,
creating a potentially deadly inflammatory response.
Symptoms
The incubation period for WNV after infection
typical ranges between 3 to 14 days. Eighty percent of
infected persons will exhibit no clinically apparent
symptoms whatsoever. Roughly 20% of infected persons will exhibit a series of mild flu-like symptoms,
also known as West Nile Fever. These mild symptoms
can persist for 3 to 6 days, possibly weeks, and include:


eye pain



fever



headache



loss of appetite



lymphadenopathy (abnormal enlargement of the
lymph nodes)



malaise (nonspecific bodily discomfort)



myalgia (nonspecific muscular pain/tenderness)



nausea



rash (on the neck, torso, and limbs)



vomiting

GALE ENCYCLOPEDIA OF MEDICINE

In rare cases, approximately 1 in 150 cases
(0.7%), WNV can cross the blood-brain barrier and
develop into a severe neuroinvasive disease.
Immunocompromised and elderly (>50 years of age)
patients are at an increased risk for developing more
severe syndromes; a 20-fold increase in incidence
among older patients. Symptoms indicating the possible presence of severe West Nile-related syndromes
include:


severe headache



high fever



acute muscle weakness



neck stiffness



convulsions and tremors



disorientation and stupor



paralysis



coma

People exposed to WNV infection, especially the
immunocompromised and elderly, should contact
their health provider immediately if they develop a
severe headache accompanied by high fever.
Typically, severe WNV syndromes manifest as
one of three syndromes: West Nile encephalitis
(inflammation of the brain); West Nile meningitis
(inflammation of the meninges of the brain and
spinal cord); or West Nile meningoencephalitis
(inflammation of both the brain and the meninges).
These three syndromes can cause severe brain
damage and even death. Severe WNV disease carries a mortality rate ranging between 3% and 15%,
with elderly patients suffering the highest mortality
rate. The majority of these deaths are as a result of
complication attributable to West Nile meningoencephalitis. Additionally, severe WNV disease can
cause acute vision loss due to inflammatory disorders of the eye, such as chorioretinitis, optic neuritis, retinal vasculitis, uveitis, and vitritis. Less
frequently, the patient can exhibit acute flaccid
paralysis, similar to poliomyelitis (polio) or
Guillain-Barré syndrome, caused by inflammation
of the spinal cord and/or damage to the peripheral
nerves. In some severe cases, this acute flaccid
paralysis can disrupt muscles that control breathing and result in respiratory failure.

Diagnosis
A proper diagnosis of WNV infection depends
heavily upon clinical presentation, laboratory testing,
and patient history. Patients with a known
3981

West Nile virus

relatively few cases of dogs and cats becoming infected
with WNV. Animals of all species exhibiting fever,
weakness, poor coordination, spasms, seizures, and/
or personality changes may be infected with WNV.

West Nile virus

susceptibility to WNV (the elderly and immunocompromised) that exhibit symptoms during the late
spring to early fall, or at any time in warmer climates,
should be tested for WNV and other arboviral infections. Additionally, health providers should remain
constantly aware of the local presence of WNV activity, such as reports of recent animal and/or human
cases. Similarities of symptomology between and serological cross-reactivity of WNV and other flaviviruses, may lead to confusion and an incorrect
diagnosis. Health providers must use thorough
laboratory testing to differentiate WNV antibodies
from those of other arboviruses.
Symptomatic WNV infection can be classified as
either non-neuroinvasive or neuroinvasive, with each
being identified according to certain criteria.
Non-neuroinvasive
The majority of WNV infections are asymptomatic. In approximately 20% of WNV cases, clinically
recognizable symptoms can manifest. However, to be
clinically classified as non-neuroinvasive West Nile
disease, the following must be true:


no neuroinvasive symptomology



presence of fever without other recognizable cause



four-fold or greater increase in serum antibody titer



virus isolated from and or deomonstrated in blood,
tissue, cerebrospinal fluid (CSF), or other bodily
fluid



virus-specific immunoglobulin M (IgM antibodies
demonstrated in CSF through antibody-capture
methods
Neuroinvasive

In the rare cases (0.7%) of West Nile disease, the
virus crosses the blood-brain barrier and manifests in
severe and life-threatening symptomology. Clinical
confirmation of neuroinvasive of neuroinvasive disease requires the presence of a fever and at least one
of the following:


acutely altered mental status, such as disorientation,
stupor, or coma



acute central or peripheral neurological difficulties,
such as paralysis, nerve palsy, sensory deficits, and
abnormal muscle function



an increased white blood cell concentration in the
CSF coupled with symptoms of meningitis, such as
severe headache and neck pain

3982

Treatment
Currently, there are no treatment modalities for
WNV infection. Instead, supportive care is utilized to
treat the varying symptoms and syndromes associated
with the various West Nile diseases. Although milder
symptoms can be treated at home, severe symptoms
can require hospitalization. Treatment of severe symptoms may require the use of intravenous infusions,
airway and respiratory management and support,
and use of preventative measures against secondary
infection.

Prognosis
The majority of WNV infections will manifest
asymptomatically. West Nile fever offers an excellent
prognosis associated with quick recovery and no
adverse side-effects. The majority of symptoms will
resolve within a few days or weeks of manifestation.
However, the prognosis is not a positive for
patients suffering the more severe syndromes attributable to WNV infection. Symptoms of West Nile encephalitis, West Nile meningitis, and West Nile
meningoencephalitis can last for several weeks, as
well as cause severe and permanent neurological
damage. Inflammation can interfere with the brain
and central nervous system and result in death, especially amongst the elderly population. Patients with
West Nile poliomyelitis may suffer prolonged muscle
weakness and loss of motor control. Long-term rehabilitation is typically required and a full recovery is not
assured. If the poliomyelitis affects muscles used for
breathing, death from respiratory failure may result.

Prevention
Although there is a vaccine used for horses and
exotic birds in zoos, there is no WNV vaccine for
humans at the current time. Several pharmaceutical
companies, however, have WNV vaccines in
development.
Prevention techniques of WNV typically coincide
with avoidance measures against mosquito bites; the
primary source of the virus. These include the use of
insect repellant (with 5% to 20% DEET) on exposed
body parts, wearing loose-fitting clothes over the
limbs and torso while outdoors, using mosquito coils
and/or citronella candles outdoors, and limiting outdoor activities during peak biting periods and/or in
areas with high mosquito density. While camping outdoors, knockdown spray or bed netting with pyrethrum is suggested. Mosquito eradication programs
have been instituted in most major cities. Public health
GALE ENCYCLOPEDIA OF MEDICINE

Flavivirus—An arbovirus that can cause potentially
serious diseases, such as dengue, yellow fever,
Japanese encaphilitis, and West Nile fever.
Guillain-Barré—A disorder in which the body’s
immune system attacks part of the peripheral
nervous system. Weakness, tingling, and abnormal
sensations in the arms and upper body can progress
until the muscles become totally disabled and the
patient is effectively paralyzed.
Meninges —A series of membranous layers of connective tissue that protect the central nervous system (brain and spinal cord). Damage or infection to
the meninges, such as in meningitis, can cause
serious neurological damage and even death.
Zoonotic diseases—Diseases caused by infectious
agents that can be transmitted between (or are
shared by) animals and humans. This can include
transmission through the bite of an insect, such as a
mosquito.

Fryer, J. ‘‘Interview with Joe Garret’’ Texas Journal of Rural
Health 20 (#3, 2001): 5-7.
O’Leary D., A. Marfin, S. Montgomery, A. Kipp, J.
Lehman, B. Biggerstaff, et al. ‘‘The Epidemic of West
Nile Virus in the United States, 2002.’’ Vector-borne and
Zoonotic Diseases 4(March 2002): 61-.
Peterson L, and J. Roehrig. ‘‘West Nile Virus: A Reemerging
Gobal Pathogen.’’ Emerging Infectious Diseases
7(July-August 2001): 611-614.
Rappole J., S. Derrickson, and Z. Hubalek. ‘‘Migratory
Birds and Spread of West Nile Virus in the Western
Hemisphere.’’ Emerging Infectious Diseases 6
(July-August 2000): 319-328.
Huhn G’, J. Sejvar, S. Montgomery, and M. Dworkin.
‘‘West Nile Virus in the United States: An Update on an
Emerging Infectious Disease.’’ American Family
Physician 68 (August 2003): 653-672.
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd, Atlanta, GA 30333. (800 )311-3435. <http://
www.cdc.gov>.

Jason Fryer

authorities can utilize United States Environmental
Protection Agency-approved ‘‘adulticidies’’ in areas
suspected of the presence of WNV.
The Culex pipiens mosquito is the primary vector
of WNV transmission and is also commonly live and
feed in urban areas. Special precautions should be
taken to reduce exposure to these potentially infected
insects. Screen doors and enclosed porches can help
keep mosquitoes from coming into the house. It should
be noted that studies have shown that mosquito control
devices such as ‘‘bug zappers’’ and CO2-baited traps do
not significantly reduce the risk of being bitten.
Removing potential mosquito breeding areas
from near the home and from the neighbourhood
can further reduce the risk of bites. Any container
which can collect half an inch of standing water can
become a potential breeding site in as little as five days.
Old tires, empty plant pots, and empty trashcans
should be removed, while water sources like ponds or
birdbaths should be cleaned regularly. Standing water
on any property should be drained, such as from
clogged eves. Swimming pools and hot tubs should
be properly covered and chlorinated to prevent mosquitoes breeding in them.
BOOKS

Mackenzie J., A.D.T. Barrett, and V. Deubel (eds.) Japanese
encephalitis and West Nile viruses Berlin: Springer, 2002.
GALE ENCYCLOPEDIA OF MEDICINE

Wheezing
Definition
Wheezing is a high-pitched whistling sound associated with labored breathing.

Description
Wheezing occurs when a child or adult tries to
breathe deeply through air passages that are narrowed
or filled with mucus as a result of:


allergy



infection



illness



irritation

Wheezing is most common when exhaling. It is
sometimes accompanied by a mild sensation of tightness in the chest. Anxiety about not being able to
breathe easily can cause muscle tension that makes
matters worse.

Causes and symptoms
Wheezing is the symptom most associated with
asthma. It can be caused by:
3983

Wheezing

PERIODICALS

KEY TERMS

Wheezing

bronchodilators are prescribed to remove excess
mucus from the breathing passages.



exposure to allergens (food, pollen, and other
substances, that cause a person to have an allergic
reaction)



fumes



ice-cold drinks, or very cold air



medication



strenuous exercise



weather changes



foreign objects trapped in the airway



cystic fibrosis, and other genetic disorders



turns blue or gray and stops breathing



respiratory illnesses such as pneumonia, bronchitis,
congestive heart failure, and emphysema



becomes extremely short of breath, and is unable to
speak



coughs up bubbly-pink or white phlegm



seems to be suffocating



develops a fever of 1018F (38.38C) or higher



wheezes most of the time, and coughs up gray or
greenish phlegm

Diagnosis
A family physician, allergist, or pulmonary specialist takes a medical history that includes questions
about allergies, or unexplained symptoms that may be
the result of allergic reactions. If the pattern of the
patient’s symptoms suggests the presence of allergy,
skin and blood tests are performed to identify the
precise nature of the problem.
A pulmonary function test may be ordered to measure the amount of air moving through the patient’s
breathing passages. X rays are sometimes indicated for
patients whose wheezing seems to be caused by
chronic bronchitis or emphysema.
In 2004, researchers in Japan discovered a new
method for diagnosing asthma in infants by testing
for certain antibodies in their sputum (mucus that
spits up from the bronchi).

Treatment
Mild wheezing may be relieved by drinking plenty
of juice, water, weak tea, and broth. Ice-cold drinks
should be avoided.
A vaporizer can help clear air passages. A steam
tent, created by lowering the face toward a sink filled
with hot water, placing a towel over the head and sink,
and inhaling the steam, can do likewise.
Bronchodilators (medications that help widen narrowed airways) may be prescribed for patients whose
wheezing is the result of asthma. Newer asthma medications taken daily can help prevent asthma attacks, as
can avoiding asthma and allergy triggers.
Antibiotics are generally used to cure acute bronchitis and other respiratory infections. Expectorants
cough-producing
medications)
or
certain
3984

If wheezing is caused by an allergic reaction, antihistamines will probably be prescribed to neutralize
body chemicals that react to the allergen.
Medical emergencies
Breathing problems can be life-threatening.
Immediate medical attention is required whenever an
individual:

Alternative treatment
Certain yoga positions (Bridge, Cobra, Pigeon,
and Sphinx) may relieve wheezing by improving
breathing control and reducing stress. Patients
whose wheezing is related to asthma, chronic bronchitis, emphysema, or a severe allergic reaction may
benefit from these techniques, but must continue to
have their condition monitored by a conventional
physician.

Prognosis
Mild wheezing caused by infection or acute illness
usually disappears when the underlying cause is
eliminated.
Some doctors believe that childhood respiratory
infections may activate parts of the immune system
that prevent asthma from developing.

Prevention
Stopping smoking can eliminate wheezing. So can
reducing or preventing exposure to other substances
that cause the problem.
Resources
PERIODICALS

‘‘Creola Bodies in Wheezing Infants Predict Asthma
Development.’’ Immunotherapy Weekly July 7,
2004: 10.
GALE ENCYCLOPEDIA OF MEDICINE

Maureen Haggerty
Teresa G. Odle

days, or weeks after the injury occurs. Symptoms of
whiplash include:


pain or stiffness in the neck, jaw, shoulders, or arms



dizziness



headache



loss of feeling in an arm or hand



nausea and vomiting

Depression and vision problems are rare symptoms of this condition.

Whiplash
Definition
Whiplash is a sudden, moderate-to-severe strain
affecting the bones, discs, muscles, nerves, or tendons
of the neck.

Description
The neck is composed of seven small bones.
Known as the cervical spine, these bones:


support the head



help maintain an unobstructed enclosure for the
spinal cord



influence the shape and structure of the spine



affect posture and balance

About 1,000,000 whiplash injuries occur in the
United States every year. Most are the result of
motor vehicle accidents or collisions involving contact
sports. When unexpected force jerks the head back,
then forward the bones of the neck snap out of position and irritated nerves can interfere with flow of
blood and transmission of nerve impulses. Pinched
nerves can damage or destroy the function of body
parts whose actions they govern.
Risk factors
Osteoarthritis of the spine increases the risk of
whiplash injury. So do poor driving habits, driving in
bad weather, or driving when tired, tense, or under the
influence of alcohol or other drugs.

Causes and symptoms
Tension shortens and tightens muscles. Fatigue
relaxes them. Either condition increases the likelihood
that whiplash will occur and the probability that the
injury will be severe.
Sometimes symptoms of whiplash appear right
away. Sometimes they do not develop until hours,
GALE ENCYCLOPEDIA OF MEDICINE

Diagnosis
Whiplash is difficult to diagnose because x rays
and other imaging studies do not always reveal
changes in bone structure. Organs affected by nerve
damage or reduced blood supply may generate symptoms not clearly related to whiplash.
Diagnosis is based on observation of the patient’s
symptoms, medical history, physical examination, and
neurological studies to determine whether the spine
has been injured.

Treatment
Medication, physical therapy, and supportive
measures are used to treat whiplash. Chiropractors
gently realign the spine to relax pinched nerves or
improve blood flow. A patient whose symptoms are
severe may wear a soft, padded collar (Thomas collar
or cervical collar) until the pain diminishes.
When pressure on the root of the nerve causes loss
of strength or sensation in a hand or arm, a cervical
traction apparatus may be recommended.
Self-care
Inflammation and cramping can be alleviated by
wrapping ice or an ice pack in a thin towel and applying it to the injured area for 10-20 minutes every hour.
After the first 24 hours, painful muscle spasms can be
prevented by alternating cold packs with heat treatments. Letting a warm shower run on the neck and
shoulders for 10-20 minutes twice a day is recommended. Between showers, warm towels or a heat
lamp should be used to warm and soothe the neck
for 10-15 minutes several times a day.
Improving posture is important, and gentle massage can be beneficial. Sleeping without a pillow promotes healing, and a cervical collar or small rolled
towel pinned under the chin can provide support and
prevent muscle fatigue.
3985

Whiplash

‘‘WhatÆs New in: Asthma and Allergic Rhinitis.’’ Pulse
September 20, 2004: 50.
‘‘Wheezing? Check Your Inhaler.’’ Prevention September
2004: 34.

White blood cell count and differential

Alcohol should be avoided. A chiropractor, primary care physician, or orthopedic specialist should be
notified whenever a painful neck injury occurs. Another
situation requiring attention is if the face or arm weaken
or become painful or numb following a neck injury.

Prognosis
With treatment, whiplash can usually be cured in
one week to three months after injury occurs. If nerve
roots are damaged, numbness and weakness may last
until recovery is complete.

Prevention
Chiropractors can recommend diet and exercise
techniques to reduce stress and tension. Careful,
defensive driving, wearing seatbelts, and using padded
automobile headrests can lessen the likelihood of
whiplash.
Resources
OTHER

Haggerty, Maureen. ‘‘Whiplash.’’ A Healthy MePage. June
7, 1998. <http://www.ahealthyme.com/topic/
topic100587681>.

Maureen Haggerty

Whipple’s disease see Malabsorption
syndrome

White blood cell count and
differential
Definition
The white blood cell count and differential determine the number of white blood cells and the percentage of each type of white blood cell in a person’s
blood. These tests are included in general health examinations and help investigate a variety of illnesses,
including infection, allergy, and leukemia.

Purpose
The white blood cell count provides a clue to the
presence of illness. White cells protect the body by
fighting infection and attacking foreign material.
When extra white cells are needed, the bone marrow
increases production.
3986

There are five types of white cells, each with different functions: neutrophils, lymphocytes, monocytes, eosinophils, and basophils. The differential
reveals if these cells are present in a normal distribution, or if one cell type is increased or decreased. This
information helps diagnose specific types of illness.
Conditions or medications that weaken the
immune system, such as AIDS or chemotherapy,
cause a decrease in white cells. The white cell count
detects dangerously low numbers of white cells.
Recovery from illness can be monitored by the
white cell count. Counts continuing to rise or fall to
abnormal levels indicate a worsening condition;
counts returning to normal indicate improvement.

Description
Neutrophils increase in response to bacterial
infection. They destroy bacteria by enveloping and
digesting them, a process called phagocytosis. When
many neutrophils are needed, they are released from
the bone marrow as immature cells, called bands or
stab cells.
Lymphocytes fight viral infections and some bacterial infections. Certain lymphocytes directly attack
invading microorganisms; others produce antibodies
that attack and destroy microorganisms and other
foreign material. Large lymphocytes, called atypical
lymphocytes, are seen during infectious mononucleosis
and other illnesses.
Monocytes increase during severe infections, and
other conditions. They remove debris and microorganisms by phagocytosis. Eosinophils and basophils
increase in response to allergic reactions and parasitic
infection.
White cell counts are usually done on an automated instrument. A sample of blood is mixed with a
chemical to burst the red blood cells. The remaining
white cells are counted by the instrument.
The differential is done by spreading a drop
of blood on a microscope slide. The slide is stained
with a special stain and examined under a microscope.
One-hundred white cells are counted and identified as
either neutrophils, bands, lymphocytes, monocytes,
eosinophils or basophils. Any atypical or immature
cells also are counted. Cells are identified by the shape
and appearance of the nucleus, the color of cytoplasm
(the background of the cell), and the presence and color
of granules. The percentage of each cell type is reported.
At the same time, red cells and platelets are examined
for abnormalities in appearance. Some instruments
perform an automated differential.
GALE ENCYCLOPEDIA OF MEDICINE

Band—Immature neutrophil.
Basophil—White blood cell that increases in
response to parasitic infections and allergic
reactions.
Differential—Blood test that determines the percentage of each type of white blood cell in a person’s blood.
Eosinophil—White blood cell that increases in
response to parasitic infections and allergic
reactions.
Leukocytosis—A white count increased to over
10,000/L.
Leukopenia—A white count decreased to less than
4,000/L.
Lymphocyte—White blood cell that fights viral and
some bacterial infections by direct attack or the
production of antibodies.
Monocyte—White blood cell that increases during
a variety of conditions including severe infections.
It removes debris and microorganisms by
phagocytosis.
Neutrophil—White blood cell that increases in
response to bacterial infection. It removes and
kills bacteria through phagocytosis.
Phagocytosis—A process by which a white blood
cell envelopes and digests debris and microorganisms to remove them from the blood.

stops reduces bruising; warm packs relieve discomfort.
The person may feel dizzy or faint.

Normal results
Total white cell count 5,000-10,000 uL.
Neutrophils
50-60%.
Lymphocytes
20-40%.
Monocytes 2-6%. Eosinophils 1-4%. Basophils 0.51%. Bands 0-3%.

Abnormal results
The white cell count and differential are interpreted according to a person’s clinical condition
and medical history. Leukocytosis (a white count
increased to over 10,000/uL) is seen in bacterial
infections, inflammation, leukemia, trauma, and
stress. Leukopenia (a white count decreased to
less than 4,000/L) is seen in some viral infections
or severe bacterial infections, and conditions that
affect the bone marrow such as dietary deficiencies,
chemotherapy, radiation therapy, and autoimmune
diseases.
Nancy J. Nordenson

Whooping cough
Definition

Both the white blood cell count (also called white
count or leukocyte count) and the differential (also
called diff) are covered by insurance. Results are available the same day.

Preparation
This test requires 7 mL of blood. A healthcare
worker ties a tourniquet on the person’s upper
arm, locates a vein in the inner elbow region, and
inserts a needle into that vein. Vacuum action
draws the blood through the needle into an
attached tube. Collection of the sample takes only
a few minutes.

Aftercare
Discomfort or bruising may occur at the puncture
site. Pressure to the puncture site until the bleeding
GALE ENCYCLOPEDIA OF MEDICINE

Whooping cough, also known as pertussis, is a
highly contagious disease which causes classic spasms
(paroxysms) of uncontrollable coughing, followed by
a sharp, high-pitched intake of air which creates the
characteristic ‘‘whoop’’ of the disease’s name.

Description
Whooping cough is caused by a bacteria called
Bordatella pertussis. B. pertussis causes its most severe
symptoms by attaching itself to those cells in the
respiratory tract which have cilia. Cilia are small,
hair-like projections that beat continuously, and
serve to constantly sweep the respiratory tract clean
of such debris as mucus, bacteria, viruses, and dead
cells. When B. pertussis interferes with this normal,
janitorial function, mucus and cellular debris accumulate and cause constant irritation to the respiratory
tract, triggering coughing and increasing further
mucus production.
3987

Whooping cough

KEY TERMS

Whooping cough

fatigue, poor appetite, and an extremely runny nose
(rhinorrhea). This stage lasts about 10-14 days.
The paroxysmal stage, lasting two to four weeks,
begins with the development of the characteristic
whooping cough. Spasms of uncontrollable coughing,
the ‘‘whooping’’ sound of the sharp inspiration of air,
and vomiting are all hallmarks of this stage. The
whoop is believed to occur due to inflammation and
mucous which narrow the breathing tubes, causing the
patient to struggle to get air into his/her lungs; the
effort results in intense exhaustion. The paroxysms
(spasms) can be induced by over activity, feeding,
crying, or even overhearing someone else cough.

A magnified image of a pertussis toxin crystal that causes
whooping cough. (National Institutes of Health/Custom Medical
Stock Photo. Reproduced by permission.)

Whooping cough is a disease which exists
throughout the world. While people of any age can
contract whooping cough, children under the age of
two are at the highest risk for both the disease and for
serious complications and death. Apparently, exposure to B. pertussis bacteria earlier in life gives a person
some immunity against infection with it later on.
Subsequent infections resemble the common cold.

Causes and symptoms
Whooping cough has four somewhat overlapping
stages: incubation, catarrhal stage, paroxysmal stage,
and convalescent stage.
An individual usually acquires B. pertussis by
inhaling droplets infected with the bacteria coughed
into the air by someone already suffering with the
infection. Incubation is the symptomless period of
seven to14 days after breathing in the B. pertussis bacteria, and during which the bacteria multiply and penetrate the lining tissues of the entire respiratory tract.
The catarrhal stage is often mistaken for an exceedingly heavy cold. The patient has teary eyes, sneezing,
3988

The mucus which is produced during the paroxysmal stage is thicker and more difficult to clear than
the more watery mucus of the catarrhal stage, and the
patient becomes increasingly exhausted attempting to
clear the respiratory tract through coughing. Severely
ill children may have great difficult maintaining the
normal level of oxygen in their systems, and may
appear somewhat blue after a paroxysm of coughing,
due to the low oxygen content of their blood. Such
children may also suffer from swelling and degeneration of the brain (encephalopathy), which is believed
to be caused both by lack of oxygen to the brain during
paroxysms, and also by bleeding into the brain caused
by increased pressure during coughing. Seizures may
result from decreased oxygen to the brain. Some children have such greatly increased abdominal pressure
during coughing that hernias result (hernias are the
abnormal protrusion of a loop of intestine through a
weak area of muscle). Another complicating factor
during this phase is the development of pneumonia
from infection with another bacterial agent; the bacteria takes hold due to the patient’s already-weakened
condition.
If the patient survives the paroxysmal stage,
recovery occurs gradually during the convalescent
stage, usually taking about three to four weeks.
However, spasms of coughing may continue to occur
over a period of months, especially when a patient
contracts a cold, or other respiratory infection.

Diagnosis
Diagnosis based just on the patient’s symptoms is
not particularly accurate, as the catarrhal stage may
appear to be a heavy cold, a case of the flu, or a simple
bronchitis. Other viruses and tuberculosis infections
can cause symptoms similar to those found during
the paroxysmal stage. The presence of a pertussislike cough along with an increase of certain specific
white blood cells (lymphocytes) is suggestive of
GALE ENCYCLOPEDIA OF MEDICINE

Cilia—Tiny, hair-like projections from a cell. In the
respiratory tract, cilia beat constantly in order to
move mucus and debris up and out of the respiratory tree, in order to protect the lung from infection
or irritation by foreign bodies.
Encephalopathy—Swelling and degeneration of
the brain.

pertussis (whooping cough). However, cough can
occur from other pertussis-like viruses. The most accurate method of diagnosis is to culture (grow on a
laboratory plate) the organisms obtained from swabbing mucus out of the nasopharynx (the breathing
tube continuous with the nose). B. pertussis can then
be identified by examining the culture under a
microscope.

Treatment
Treatment with the antibiotic erythromycin is helpful only at very early stages of whooping cough, during
incubation and early in the catarrhal stage. After the
cilia and the cells bearing those cilia, are damaged, the
process cannot be reversed. Such a patient will experience the full progression of whooping cough symptoms;
symptoms will only improve when the old, damaged
lining cells of the respiratory tract are replaced over
time with new, healthy, cilia-bearing cells. However,
treatment with erythromycin is still recommended, to
decrease the likelihood of B. pertussis spreading. In fact,
all members of the household where a patient with
whooping cough lives should be treated with erythromycin to prevent the spread of B. pertussis throughout
the community. The only other treatment is supportive,
and involves careful monitoring of fluids to prevent
dehydration, rest in a quiet, dark room to decrease
paroxysms, and suctioning of mucus.

other pre-existing conditions, so that the patient is
already in a relatively weak, vulnerable state (such
conditions may include low birth weight babies, poor
nutrition, infection with the measles virus, presence of
other respiratory or gastrointestinal infections or
diseases)

Prevention
The mainstay of prevention lies in programs similar
to the mass immunization program in the United States
which begins immunization inoculations when infants
are two months old. The pertussis vaccine, most often
given as one immunization together with diphtheria and
tetanus, has greatly reduced the incidence of whooping
cough. Unfortunately, there has been some concern
about serious neurologic side effects from the vaccine
itself. This concern led huge numbers of parents in
England, Japan, and Sweden to avoid immunizing
their children, which in turn has led to major epidemics
of disease in those countries. However, several carefully
constructed research studies have disproved the idea
that the pertussis vaccine is the cause of neurologic
damage. Furthermore, a newer formulation of the
pertussis vaccine is available. Unlike the old whole cell
pertussis vaccine, which is composed of the entire
bacterial cell which has been deactivated (and
therefore unable to cause infection), the newer acellular
pertussis vaccine does not use a whole cell of the bacteria, but is made up of (between two and five)
chemical components of the B. pertussis bacteria. The
acellular pertussis vaccine appears to greatly reduce the
risk of unpleasant reactions to the vaccine, including
high fever and discomfort following vaccination.
Resources
PERIODICALS

Jenkinson, Douglas. ‘‘Natural Course of 500 Consecutive
Casesof Whooping Cough: A General Practice
Population Study.’’ British Medical Journal310, no.
6975 (February 4, 1995): 299+.

Rosalyn Carson-DeWitt, MD

Prognosis
Just under 1% of all cases of whooping cough cause
death. Children who die of whooping cough usually have
one or more of the following three conditions present:


severe pneumonia, perhaps with accompanying
encephalopathy



extreme weight loss, weakness, and metabolic
abnormalities due to persistent vomiting during paroxysms of coughing

GALE ENCYCLOPEDIA OF MEDICINE

Wilderness medicine
Definition
Wilderness medicine encompasses the prevention,
diagnosis, and treatment of injuries and medical
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KEY TERMS

Wilderness medicine

conditions that may occur during activities in remote
territories.

Purpose
Activities that may require wilderness medicine
include backpacking, cross-country skiing, mountaineering, white water rafting, scuba diving, and
exploration in undeveloped regions such as deserts or
jungles. Wilderness medicine has evolved to deal with
situations in which definitive medical care is hours or
days away, and in which patients may require quick or
extended attention. Wilderness medicine utilizes first
aid techniques, but requires additional skills that take
into account demanding environments, uncommon
threats to health, hazardous or lengthy travel to medical facilities, and difficulties in obtaining food, water,
and shelter.
Wilderness medicine uses techniques to assess and
treat a variety of conditions and injuries, including:


wounds and burns



external and internal bleeding



cardiac arrest



head injuries



spinal cord injuries



fractures and dislocations



altitude sickness



problems from cold and heat



allergic and anaphylactic reactions



lightning strikes



near drowning



insect, reptile and animal bites



poisoning



emergency child birth

Precautions
In wilderness situations caregivers should follow
the maxim of first, do no harm. Uninjured members of
groups should not attempt rescues that place themselves in danger. People administering first aid or wilderness medicine should remain calm and organized at
all times. Only those with experience should administer medications and medical procedures. Injured people should not be moved until they are fully evaluated,
or unless environmental conditions are threatening
and require immediate shelter.
People with certain medical conditions should
avoid travel in the wilderness, which can make existing
3990

conditions worse. These conditions include metastatic
cancer, peptic ulcers, coronary artery disease, chronic
obstructive pulmonary disease, clotting or bleeding
disorders, high-altitude sickness, chronic rheumatoid
arthritis, chronic severe back pain, and chronic knee
and hip joint disease.

Description
The first stage of wilderness medicine begins with
an assessment of the injury or condition. Primary
assessment is used to quickly determine if a patient is
in a life-threatening situation and to provide immediate emergency care. Secondary assessment is the thorough evaluation of a patient after life-threatening
circumstances are relieved.
Primary assessment
A rule of thumb for the first steps of primary
assessment, recommended by the Wilderness
Medicine Institute, is the ABCDE procedure. It stands
for Airway, Breathing, Circulation, Disability, and
Exposure assessment. First, a patient’s airway should
be checked by close observation of whether or not air
can move in and out and any obstructions to breathing
should be alleviated. In unconscious people the tongue
can often fall to the back of the throat and block
breathing and the head should be tilted back and the
lower jaw raised to alleviate the obstruction. If neck or
spinal cord injuries are suspected, the head must be
handled with extreme care to avoid further injury to
the delicate spinal cord. In these cases, the lower jaw
can be pulled forward to open the airway. If the neck is
severely out of alignment due to an injury or fall, it
may be gently realigned to free the airway.
After the airway is cleared and breathing is
ensured, a patient’s circulation is checked by noting
the pulse of the carotid artery, on the neck, the pulse
of the femoral artery in the front groin, and by listening to the heartbeat. If pulse is lacking, cardiopulmonary resuscitation (CPR) may be required, which
requires chest compression and mouth-to-mouth
breathing. Circulation checks include surveying a
patient for bleeding. If severe bleeding is present, it
should be stopped by direct pressure to the injured
area, and by elevating the wound level to the heart if
possible.
Disability assessment means checking for
damage to the spinal cord, particularly in the cervical
region of the neck. Assessment of exposure determines if environmental conditions, such as heat or
cold, are immediate threats to a patient’s life, which
GALE ENCYCLOPEDIA OF MEDICINE

Secondary assessment
During this stage, a thorough physical examination of the patient is made from head to toe to determine the extent of injuries or problems. Caretakers
performing the assessment should write detailed
notes in order to inform physicians or emergency
workers later. Patients are thoroughly interviewed
to determine the scope of problems and any previous
medical issues that might be related. Patients should
be spoken to calmly to determine their mental states
and how well they respond to stimuli. Vital signs such
as heart rate and respiration rate should be noted and
monitored. The skin should be carefully observed for
injuries, boils, rashes, and discoloration. Red or
flushed skin may indicate fever or heat-related
conditions, while pale or blotchy skin can point to
shock or hypothermia. A bluish tint to the skin may
mean a lack of oxygen. Contact lenses should be
removed from patients in cold conditions, as they
can freeze to the eyes. During secondary assessment
the patient should be closely monitored over time
until improvement is noted or further treatment
decisions are made. At all times in wilderness
injuries, shock must be watched for and immediately
treated.
Shock
In wilderness situations shock should be suspected
after traumatic injuries, significant loss of blood due to
internal or external bleeding, extreme loss of fluids
from vomiting or diarrhea, heart attacks, and spinal
cord injuries. Shock is easiest to alleviate when it is
treated early; when not treated properly, it can progress
to unconsciousness and death. When the likelihood of
shock occurs, patients should be continually monitored
and supported.
Symptoms of shock begin with anxiety and restlessness, with increased heart rates and labored, shallow breathing. Shock victims tend to sweat profusely
with cool and clammy skin. Thirst and nausea are also
symptoms.
Shock is treated in the wilderness by maintaining
an open airway for the patient to breathe, by treating
any injuries such as bleeding wounds, by reducing pain
if possible, and by replenishing fluids. Patients should
be kept calm and warm and their feet should be elevated if possible to increase blood flow to the organs.
If shock symptoms progress, plans should be quickly
made to get help or evacuate the patient.
GALE ENCYCLOPEDIA OF MEDICINE

Evacuation
Evacuation of a patient may be a crucial decision
in the wilderness, depending upon the severity of an
injury or condition, the difficulty of moving the
patient, the time considerations involved, and the
availability of outside help. In general if a patient
with severe symptoms is not improving despite care
then evacuation becomes necessary. The Wilderness
Medical Society lists symptoms that require postponing travel or evacuating patients:


progressive deterioration with symptoms of dizziness, fainting, abnormally slow (bradycardia) or fast
(tachycardia) heart rate, labored breathing, poor
mental status, progressive weakness, constant vomiting or diarrhea, intolerance of oral fluids, or recurrent loss of consciousness due to head injuries



debilitating pain



inability to sustain pace due to medical problems



passage of blood by mouth or rectum



symptoms of serious high-altitude illness



infections that get worse despite treatment



chest pain that is not musculoskeletal in origin



psychological status threatening the individual or
group

If a patient cannot be moved without risk of
further injury, then other members of a party, preferably two or more, should be sent to get outside help.
When requesting outside assistance, the safety of
incoming rescuers and time constraints should be
weighed. Requests for outside help should be made
in writing, and include an assessment of the patient
and situation as well as a detailed location of the
incident. In some regions, helicopter evacuation may
be an option, and should be used if an injury is lifethreatening.
During evacuation patients must be handled with
extreme care, as well as insulated from heat, cold and
further injuries. Larger wilderness expeditions may
have special devices available for transporting injured
members, while smaller parties may have to improvise
transporting devices by using backpacks, ropes and
other available materials.
Wounds and burns
In wilderness situations wound management
strives to stop bleeding, prevent infection, and speed
healing. Bleeding from wounds should be controlled
by direct pressure. Wounds and burns should be
cleaned gently and thoroughly, treated with antibiotic
3991

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may require actions such as seeking shelter or covering the patient with protective clothing.

Wilderness medicine

ointment, and covered with bandages to avoid infections. Wounds that have high risks of infections, such
as large cuts, open fractures, and animal bites, should
be watched closely.
External and internal bleeding
External bleeding should be stopped by direct
pressure, such as firmly applying a clean bandage or
compress to an open wound. Secondary pressure may
be applied to pressure points, such as the large arteries
in the upper arm or groin, to slow bleeding.
Tourniquets are recommended only in life-threatening
situations, as they can cause complications and infections. Symptoms of internal bleeding include dizziness, fainting, rapid heartbeat, weak pulse, shortness
of breath, thirst, loss of color, vomiting blood, blood in
the feces or urine, and severe pain or swelling in the
abdomen. If internal bleeding is suspected, medical
help should be sought immediately. With all cases of
significant blood loss, shock must be carefully
considered.
Cardiac arrest
Cardiac arrest in the wilderness may require CPR,
although CPR is less effective in remote regions that
lack access to the life support technology that ambulances quickly supply. CPR should be administered to
patients who have suffered near drowning, hypothermia, lightning strikes, and drug overdoses. CPR generally should not be administered in the wilderness if it
endangers the rescuers, if the time of the cardiac arrest
is unknown, if the patient appears to be dead or rigor
mortis has set in, or if cardiac arrest was caused by
severe trauma or lethal injuries.
Head injuries
Head injuries that do not cause loss of consciousness in the victim are rarely dangerous. Short-term loss
of consciousness following head injuries is known as
concussion, and these patients should be closely monitored for 24 hours, including waking them every three
hours during sleep to check for mental alertness. For
head injuries that cause prolonged unconsciousness,
the airway and cervical spine must be protected.
Severe brain injury is indicated by relapses into unconsciousness, bad headaches, bleeding from the ears,
clear fluid draining from the nose, vomiting, persistent
disorientation, personality changes, seizures, irregular
heartbeat and breathing, and unequal or unreactive
pupils. Severe head injuries must be treated by seeking
immediate medical help or evacuation.
3992

Spinal cord injuries
If spinal cord injuries are suspected, patients must
be immobilized. Some expeditions or rescue teams
may carry special splints or vests in their medical
kits. If no such equipment is available, spineboards
may be fashioned from available materials such as
backpacks, poles, or ice axes to prevent unnecessary
movement of the injured backbone.
Fractures and dislocations
Wilderness care for fractures recommends immobilization by using splints and slings. If manufactured
splints and slings are not available in the medicine kit,
they can be improvised by using natural materials, ski
poles, ice axes, clothing, or parts of backpacks. In the
case of dislocations, standard wilderness procedure is
to splint, tape and stabilize the injury in the current
position. However, if circulation or nerve function is
impaired, or if the injured person is in extreme pain,
relocation may be necessary by realigning the injured
area. Relocation is most effective if it is done immediately following the injury, before stiffness or muscle
spasms set in.
Altitude sickness
Symptoms of altitude sickness include headache,
nausea, fatigue, vomiting, and bluish skin. Ataxia, or
loss of muscular control and balance indicates more
severe altitude sickness. Altitude sickness can occur
at altitudes above 8,000 feet. The best prevention of
the condition is allowing plenty of time for acclimatization at high altitudes, drinking plenty of fluids,
and eating a diet rich in carbohydrates. Aspirin
or acetaminophen may be taken, while the drug
acetazolamide (Diamox) can relieve symptoms of
mild acute mountain sickness (AMS). Other
related conditions, which can cause death, are high
altitude cerebral edema (HACE), which causes
fluid accumulation on the brain, and high altitude
pulmonary edema (HAPE), which causes fluid in
the lungs. The main treatment for acute mountain
sickness is to rapidly descend to lower altitudes.
In some cases oxygen may be available to ease
symptoms.
Problems from cold and heat
Frostbite is localized tissue damage from exposure
to cold, and is remedied by the slow warming of exposed
parts, preferably in heated water. Hypothermia is the
condition resulting from lowered body core temperature, and is a common affliction in wilderness medicine.
Mild hypothermia occurs when the body’s core
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Even cases of the mildest hypothermia must be
cared for closely. Patients in whom hypothermia is
suspected should be immediately warmed by gently
removing wet clothing and providing dry clothing, blankets and shelter. They should be monitored for body
temperature changes. Severe hypothermia cannot be
remedied in the wilderness; victims must be immediately
and gently evacuated. Warming severe hypothermia
victims too quickly is dangerous. Cardiopulmonary
resuscitation (CPR) may be initiated on victims of severe
hypothermia who have cardiac arrest. In cases of near
drowning, hypothermia must always be suspected.
Illness from heat includes heat exhaustion and the
more severe heat stroke. Symptoms include confusion,
rapid weak pulse, cramps, dizziness, nausea, diarrhea,
headache, and high measured temperatures. Sweating
may or may not occur, and the skin may be clammy
and blotched. The principle treatment for heat illness
in the wilderness is immediate cooling of the patient,
by providing shade, fanning, sponging and immersion
in cold water. Heat exhaustion will correct itself with
enough rest and water. Heat stroke is life threatening
and requires immediate cooling and rehydration with
fluids, preferably intravenous ones. Prevention of heat
illness includes proper conditioning, protective clothing, and avoiding dehydration.
Insect, reptile, and animal bites
Wilderness medicine must deal with an array of
bites and stings, from bears, snakes, reptiles, spiders,
scorpions, bees, fish and ticks. Prevention includes
knowledge of the threats in the region being explored,
as well as packing appropriate supplies such as bee sting
kits for anaphylactic shock and snakebite kits for venomous attacks. The goal of treatment is to stop bleeding,
prevent infection, and alleviate envenomation, or exposure to poison. The Sawyer Extractor is a suction tool
used to remove snake venom, while the Epipen and
Ana-kit are available by prescription for anaphylactic
shock due to stings and severe allergic reactions.

Preparation
Knowledge and sound planning can be the difference between success and disaster in the backcountry.
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Anaphylactic shock—Severe allergic reaction
characterized by airway constriction, tissue swelling, and lowered blood pressure.
Cardiac arrest—Heart failure or heart attack.
Dislocation—Displacement of bones at a joint.
Envenomation—Exposure to venom by bites or
stings from insects, reptiles, and fish.
Wilderness—Large backcountry areas lacking
roads, communication and other modern
infrastructure.

Members of extended wilderness outings should
undergo thorough examinations by their physicians
and dentists prior to undertaking expeditions. People
going on wilderness outings should begin in a state of
sound physical fitness by undertaking appropriate
conditioning programs, as well as becoming acclimatized to special conditions such as altitude or extreme
temperatures. Those with medications should be
aware of potential side effects and complications,
and inform other members of their group. At least
two, and preferably all, members of wilderness
expeditions should be familiar with first aid, wilderness medicine and rescue procedures. All members of
wilderness outings should carry appropriate clothing,
equipment, food, water, and first aid supplies. Trip
itineraries should be recorded with park rangers or
other official services. Means of communication with
rescue facilities should be considered in advance in
case emergencies arise.
Carrying adequate medical supplies is a crucial
preparation for wilderness outings. These supplies
will vary depending on the length of the trip and the
region. Medical kits should contain basic first aid
supplies such as bandages, dressings, pain relievers,
water purification tablets, sunscreen, antiseptics,
and ointments. Additional medical supplies include
antibiotics, medications for gastrointestinal problems,
antihistamines and emergency kits for asthma or allergic
reactions, snake and insect bite kits, splints, and basic
surgical supplies. Extended expeditions or those facing
extreme conditions might include intravenous fluids,
oxygen bottles for altitude problems, rescue gear and
evacuation equipment, and specific medications for
regional diseases and infections, such as malaria.
Immunizations are a very important preparation
for those entering wilderness areas, particularly in
3993

Wilderness medicine

temperature (measured rectally) falls from normal to
958F (358C) Fahrenheit. Moderate hypothermia gives
temperatures between 90-958F (32.2-358C), while severe
hypothermia occurs when a body’s core temperature
falls below 908F (32.28C). Symptoms include severe
shivering, confusion, apathy, drowsiness, slurred
speech, and impaired reflexes, and progresses to the
point of unconsciousness.

Wilms’ tumor

Third World countries. Immunizations should be
planned as far in advance as possible, as some
take several weeks to become effective and others
cannot be given together. Some immunizations that
may be required, depending on the region, include
tetanus, poliovirus, measles, mumps, rubella, cholera,
yellow fever, meningococcus, hepatitis, bubonic
plague, typhoid fever and rabies. See Resources below
for sources of specific immunization information.
Several organizations provide training and certification for various levels of wilderness medicine. The
most basic levels of preparation are first aid and first
responder certifications, followed by outdoor emergency care (OEC) training. More rigorous training
provides the wilderness first responder (WFR), the
wilderness emergency medical technician (WEMC),
or the wilderness prehospital emergency care
(WPHEC) certifications. The most advanced level of
wilderness medical certification is search and rescue
(SAR) emergency care, which provides expertise in a
sophisticated array of rescue techniques and
equipment.
Resources
BOOKS

Auerbach, Paul, MD. Medicine for the Outdoors. New York:
The Lyons Press, 1999.
ORGANIZATIONS

International Association for Medical Assistance to
Travelers (IAMAT). 417 Center St., Lewistown, NY
14092. (716) 754-4883.
U.S. Centers for Disease Control. 1600 Clifton Road NE,
Atlanta, GA 30333. (404) 639-1610. <http://
www.cdc.gov>. Publishes Health Information for
International Travel.
Wilderness Medical Society. PO Box 2463, Indianapolis, IN
46204. (317) 631-1745.
Wilderness Medicine Institute. PO Box 9, 413 Main Street,
Pitkin, CO 81241. (970) 641-3572. <http://
www.wildernessmed.com>.

Douglas Dupler, MA

Description
When an unborn baby is developing, the kidneys
are formed from primitive cells. Over time, these cells
become more specialized. The cells mature and organize into the normal kidney structure. Sometimes,
clumps of these cells remain in their original, primitive
form. If these cells begin to multiply after birth, they
may ultimately form a large mass of abnormal cells.
This is known as a Wilms’ tumor.
Wilms’ tumor is a type of malignant tumor. This
means that it is made up of cells that are significantly
immature and abnormal. These cells are also capable
of invading nearby structures within the kidney and
traveling out of the kidney into other structures.
Malignant cells can even travel through the body to
invade other organ systems, most commonly the lungs
and brain. These features of Wilms’ tumor make it a
type of cancer that, without treatment, would eventually cause death. However, advances in medicine
during the last 20 years have made Wilms’ tumor a
very treatable form of cancer.
Wilms’ tumor occurs almost exclusively in young
children. The average patient is about three years old,
although cases have been reported in infants younger
than six months and adults in their early twenties.
Females are only slightly more likely than males to
develop Wilms’ tumors. In the United States, Wilms’
tumor occurs in 8.3 individuals per million in white
children under the age of 15 years. The rate is higher
among African-Americans and lower among AsianAmericans. Wilms’ tumors are found more commonly
in patients with other types of birth defects. These
defects include:


absence of the colored part (the iris) of the eye
(aniridia)



enlargement of one arm, one leg, or half of the face
(hemihypertrophy)



certain birth defects of the urinary system or genitals



certain genetic syndromes (WAGR syndrome,
Denys-Drash syndrome, and Beckwith-Wiedemann
syndrome)

Causes and symptoms

Wilms’ tumor
Definition
Wilms’ tumor is a cancerous tumor of the kidney
that usually occurs in young children. It is named for
Max Wilms, a German surgeon (1867–1918) and is
also known as a nephroblastoma.
3994

The cause of Wilms’ tumor is not completely
understood. Because 15% of all patients with this
type of tumor have other heritable defects, it seems
clear that at least some cases of Wilms’ tumor are due
to an inherited alteration. A genetic defect known as
WT1, the Wilms’ tumor suppressor gene, has been
identified in some patients on chromosome 11. It
GALE ENCYCLOPEDIA OF MEDICINE

Wilm’s tumor

Researchers have found evidence that certain
types of lesions occur before the development of the
Wilms’ tumor. These lesions usually appear in the
form of stromal, tubule, or blastemal cells.

Diagnosis
Children with Wilms’ tumor generally first present to physicians with a swollen abdomen or with an
obvious abdominal mass. The physician may also find
that the child has fever, bloody urine, or abdominal
pain. The physician will order a variety of tests before
imaging is performed. These tests mostly involve
blood analysis in the form of a white blood cell
count, complete blood count, platelet count, and
serum calcium evaluation. Liver and kidney function
testing will also be performed as well as a urinalysis.

Wilm’s tumor. (Illustration by Argosy, Inc.)

appears that the tendency to develop a Wilms’ tumor
can run in families. In fact, about 1.5% of all children
with a Wilms’ tumor have family members who have
also had a Wilms’ tumor. The genetic mechanisms
associated with the disease are unusually complex; it
is thought as of 2004 that the tumor develops because
the defective WT1 gene fails to stop its growth. Other
genes that have been linked to Wilms’ tumor are
located on chromosomes 16q, 7p15, and 17q12.
Some patients with Wilms’ tumor experience
abdominal pain, nausea, vomiting, high blood pressure, or blood in the urine. However, the parents of
many children with this type of tumor are the first to
notice a firm, rounded mass in their child’s abdomen.
This discovery is often made while bathing or dressing
the child and frequently occurs before any other symptoms appear. Rarely, a Wilms’ tumor is diagnosed
after there has been bleeding into the tumor, resulting
in sudden swelling of the abdomen and a low red blood
cell count (anemia).
GALE ENCYCLOPEDIA OF MEDICINE

Initial diagnosis of Wilms’ tumor is made by looking at the tumor using various imaging techniques.
Ultrasound and computed tomography scans (CT
scans) are helpful in diagnosing Wilms’ tumor.
Intravenous pyelography, where a dye injected into a
vein helps show the structures of the kidney, can also
be used in diagnosing this type of tumor. Final diagnosis, however, depends on obtaining a tissue sample
from the mass (biopsy), and examining it under a
microscope in order to verify that it has the characteristics of a Wilms’ tumor. This biopsy is usually done
during surgery to remove or decrease the size of the
tumor. Other studies (chest x rays, CT scan of the
lungs, bone marrow biopsy) may also be done in
order to see if the tumor has spread to other locations.

Treatment
In the United States, treatment for Wilms’ tumor
almost always begins with surgery to remove or
decrease the size of the kidney tumor. Except in
patients who have tumors in both kidneys, this surgery
usually will require complete removal of the affected
kidney. During surgery, the surrounding lymph nodes,
the area around the kidneys, and the entire abdomen
will also be examined. While the tumor can spread to
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Wilms’ tumor

About 4–5% of Wilms’ tumor cases involve both
kidneys during the initial evaluation. The tumor
appears on either side equally. When pathologists
look at these tumor cells under the microscope, they
see great diversity in the types of cells. Some types of
cells are associated with a more favorable outcome in
the patient than others. In about 15% of cases, physicians find some degree of cancer spread (metastasis).
The most common sites in the body where metastasis
occurs are the liver and lungs.

Wilms’ tumor

these surrounding areas, it is less likely to do so compared to other types of cancer. In cases where the tumor
affects both kidneys, surgeons will try to preserve the
kidney with the smaller tumor by removing only a
portion of the kidney, if possible. Additional biopsies
of these areas may be done to see if the cancer has
spread. The next treatment steps depend on whether/
where the cancer has spread. Samples of the tumor are
also examined under a microscope to determine particular characteristics of the cells making up the tumor.
Information about the tumor cell type and the
spread of the tumor is used to decide the best kind of
treatment for a particular patient. Treatment is
usually a combination of surgery, medications used
to kill cancer cells (chemotherapy), and x rays or
other high-energy rays used to kill cancer cells (radiation therapy). These therapies are called adjuvant
therapies, and this type of combination therapy has
been shown to substantially improve outcome in
patients with Wilms’ tumor. It has long been known
that Wilms’ tumors respond to radiation therapy.
Likewise, some types of chemotherapy have been
found to be effective in treating Wilms’ tumor. These
effective drugs include dactinomycin, doxorubicin,
vincristine, and cyclophosphamide. In rare cases,
bone marrow transplantation may be used.
The National Wilms’ Tumor Study Group
(NWTSG) has developed a staging system to describe
Wilms’ tumors. All of the stages assume that surgical
removal of the tumor has occurred. Stage I involves
‘‘favorable’’ Wilms’ tumor cells and is usually treated
successfully with combination chemotherapy involving dactinomycin and vincristine and without
abdominal radiation therapy. Stage II tumors involving a favorable histology (cell characteristics) are
usually treated with the same therapy as Stage I.
Stage III tumors with favorable histology are usually
treated with a combination chemotherapy with doxorubicin, dactinomycin, and vincristine along with
radiation therapy to the abdomen. Stage IV disease
with a favorable histology is generally treated with
combination chemotherapy with dactinomycin, doxorubicin, and vincristine. These patients usually
receive abdominal radiation therapy and lung radiation therapy if the tumor has spread to the lungs.
In the case of Stage II through IV tumors with
unfavorable, or anaplastic, cells, then the previouslymentioned combination chemotherapy is used along
with the drug cyclophosphamide. These patients
also receive lung radiation therapy if the tumor has
spread to the lungs. Another type of tumor cell can be
present in Stages I through IV. This cell type is called
clear cell sarcoma of the kidney. If this type of cell is
3996

KEY TERMS
Biopsy—A procedure in which a small sample of
tissue is removed, prepared, and examined with a
microscope to determine the characteristics of the
tissue’s cells.
Blastemal—An immature material from which
cells and tissues develop.
Cancer—A process where abnormal cells within
the body begin to grow out of control, acquire the
ability to invade nearby structures, and travel
through the bloodstream in order to invade distant
structures.
Malignant—Refers to cancer or cancer cells.
Sarcoma—A type of cancer that originates from
connective tissue such as bone or muscle.
Stromal—A type of tissue that is associated with the
support of an organ.
Tubule—Tissues and cells associated with the
structures that connect the renal pelvis to the
glomeruli.

present, then patients receive combination therapy
with vincristine, doxorubicin, and dactinomycin. All
of these patients receive abdominal radiation therapy
and lung radiation therapy if the tumor has spread to
the lungs.
As of 2004, there are significant differences
between the treatment protocols of the NWTSG and
its European counterpart, the Société Internationale
d’Oncologie Pédiatrique (SIOP). Whereas American
practice favors surgery followed by chemotherapy,
European oncologists use preoperative chemotherapy
and stage the tumor at the time of surgery rather than
at the point of initial imaging studies.

Prognosis
The prognosis for patients with Wilms’ tumor is
quite good, compared to the prognosis for most types
of cancer. One German study reported the overall
five-year survival rate to be 89.5%. The patients who
have the best prognosis are usually those who have a
small-sized tumor, a favorable cell type, are young
(especially under two years old), and have an early
stage of cancer that has not spread. Modern treatments have been especially effective in the treatment
of this cancer. Patients with the favorable type of cell
have a long-term survival rate of 93%, whereas those
GALE ENCYCLOPEDIA OF MEDICINE

Prevention
There are no known ways to prevent a Wilms’
tumor, although it is important that children with
birth defects associated with Wilms’ tumor be carefully monitored.

National Wilms Tumor Study Group (NWTSG). Fred
Hutchinson Cancer Research Center, 1100 Fairview
Avenue North, P. O. Box 19024, Seattle, WA 981091024. (800) 553-4878. Fax: (206) 667-6623. <http://
www.nwtsg.org>.
OTHER

Online Mendelian Inheritance in Man (OMIM). #194070.
‘‘Wilms Tumor 1; WT1.’’ <http://www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=194070>.

Mark A. Mitchell, M.D.
Rebecca J. Frey, PhD

Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Wilms’ Tumor (Nephroblastoma).’’ In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
Black, Timothy L. ‘‘Wilms’ Tumor.’’ In Dambro: Griffith’s
5-Minute Clinical Consult. Philadelphia: J.B.
Lippincott, 1999.
DeVita, Vincent J., et al., editors. ‘‘Wilms’ Tumor.’’ In
Cancer: Principles and Practice of Oncology.
Philadelphia: J. B. Lippincott Company, 2001.
PERIODICALS

Boglino, C., A. Inserra, S. Madafferi, et al. ‘‘A SingleInstitution Wilms’ Tumor and Localized
Neuroblastoma Series.’’ Acta Paediatrica
Supplementum 93 (May 2004): 74–77.
Coppes, Max J., and Kathy Pritchard-Jones. ‘‘Principles of
Wilms’ Tumor Biology.’’ Urologic Clinics of North
America 27 (August 2000).
Emerson, R. E., T. M. Ulbright, S. Zhang, et al.
‘‘Nephroblastoma Arising in a Germ Cell Tumor of
Testicular Origin.’’ American Journal of Surgical
Pathology 28 (May 2004): 687–692.
Glick, R. D., M. J. Hicks, J. G. Nuchtern, et al. ‘‘Renal
Tumors in Infants Less Than 6 Months of Age.’’
Journal of Pediatric Surgery 39 (April 2004): 522–525.
Neville, Holly L., and Michael L. Ritchey. ‘‘Wilms’ Tumor.’’
Urologic Clinics of North America 27 (August 2000).
Weirich, A., R. Ludwig, N. Graf, et al. ‘‘Survival in
Nephroblastoma Treated According to the Trial and
Study SIOP-9/GPOH with Respect to Relapse and
Morbidity.’’ Annals of Oncology 15 (May 2004):
808–820.
ORGANIZATIONS

American Cancer Society. 1515 Clifton Rd. NE,
Atlanta, GA 30329. (800) 227-2345. <http://
www.cancer.org>.
March of Dimes Birth Defects Foundation, National Office.
1275 Mamaroneck Ave., White Plains, NY 10605.
<http://www.modimes.org>.
National Cancer Institute (National Institutes of Health).
9000 Rockville Pike, Bethesda, MD 20892. (800) 4226237. <http://www.nci.nih.gov\>.
GALE ENCYCLOPEDIA OF MEDICINE

Wilson disease
Definition
Wilson disease, or WD, is a rare inherited disorder
that causes excess copper to accumulate in the body. It
is also known as hepatolenticular degeneration.
Steadily increasing amounts of copper circulating in
the blood are deposited primarily in the brain, liver,
kidneys, and the cornea of the eyes. WD is fatal if it is
not recognized and treated. It is named for an
American neurologist, Samuel A. K. Wilson, who
first described it in 1912.

Description
Under normal conditions, copper that finds its
way into the body through the diet is processed within
the liver. This processed form of copper is then passed
into the gallbladder, along with the other components
of bile (a fluid produced by the liver, which enters the
small intestine in order to help in digestive processes).
When the gallbladder empties its contents into the first
part of the small intestine (duodenum), the copper in
the bile enters and passes through the intestine with
the waste products of digestion. In healthy individuals,
copper is then passed out of the body in stool.
In Wilson disease, copper does not pass from the
liver into the bile, but rather begins to accumulate
within the liver. As copper levels rise in the liver, the
damaged organ begins to allow copper to flow into the
bloodstream, where it circulates. Copper is then
deposited throughout the body, building up primarily
in the kidneys, the brain and nervous system, and the
eyes. Wilson disease, then, is a disorder of copper
poisoning occurring from birth.
3997

Wilson disease

with anaplasia have a long-term survival rate of 43%
and those with the sarcoma form have a survival rate
of 36%.

Wilson disease

Wilson disease affects approximately one in 30,000
to one in 100,000 individuals and can affect people
from many different populations. Approximately one
in 90 individuals are carriers of the gene for Wilson
disease.

Causes and symptoms
Wilson disease is inherited in an autosomal recessive manner. Autosomal recessive refers to the pattern
of inheritance where each parent carries a gene for the
disease on one of his or her chromosome pairs. When
each parent passes on the chromosome with the gene
for Wilson disease, the child will be affected with the
disease. Both males and females can be affected with
Wilson disease. If an individual is a carrier of the
Wilson disease gene they do not have any symptoms
of this disease. In order to be affected, an individual
must inherit two copies of the gene, one from each
parent. Many cases of Wilson disease may not be
inherited but occur as a spontaneous mutation in
the gene.
The gene for Wilson disease is located on chromosome number 13. The name of the gene is called
ATP7B and is thought to be involved in transporting
copper. As of 2004, over 200 different mutations of
this gene have been identified, making diagnosis by
genetic testing difficult.
Symptoms typically present between the ages of
three and 60, with age 17 considered to be the average
age a diagnosis is made. About half of all patients
experience their first symptoms in the liver. The illness
causes swelling and tenderness of the liver, sometimes
with fever, mimicking more common disorders, such
as viral hepatitis and infectious mononucleosis.
Abnormal levels of circulating liver enzymes reveal
that the liver is being seriously damaged. This form
of damage is referred to as fatty degeneration.
Without medical intervention, the liver damage
will progress to actual cirrhosis. An often-fatal manifestation of liver disease is called fulminant hepatitis.
This extremely severe inflammation of the liver
(hepatitis) results in jaundice, fluid leaking into the
abdomen, low protein circulating in the blood,
abnormalities of the blood clotting system, swelling
of the brain, and anemia due to the abnormal destruction of red blood cells.
Neurological symptoms are the first to occur in
half of all patients due to copper accumulation in the
brain and nervous system. The average age of onset for
neurological symptoms is 21. These symptoms include
tremors of the hands, uncontrollable movements of the
limbs, stiffness, drooling, difficulty swallowing,
3998

difficulty talking, and headache. There is no change
in patient’s intelligence.
About one third of all patients with Wilson disease have a variety of psychiatric symptoms as the first
signs of the disease. These symptoms include inability
to cope, depression, irritability, increased anger, and
inappropriate behavior. Often times patients have
trouble completing tasks at work or in school.
Other symptoms that can affect patients with
Wilson disease, and may occur before or after a diagnosis has been made include joint disorders, symptoms
of arthritis and skeletal problems such as osteoporosis.
Patients have occasionally been affected with kidney
stones, abnormal handling of glucose in their body
and women have menstrual cycle irregularities including stopping their regular cycle temporarily.

Diagnosis
The diagnosis of Wilson disease can be performed
relatively easily through several different tests; however, because Wilson disease is so rare, diagnosis is
often unfortunately delayed. The tests used to diagnose Wilson disease can be performed on patients who
have and who have not already shown symptoms of
the disease. It is extremely important to make a diagnosis as soon as possible since liver damage can occur
before there are any signs of the disease.
An easy way to diagnose Wilson disease is to
measure the amount of a glycoprotein found in the
blood called ceruloplasmin. Low levels of ceruloplasmin can diagnose the disease in about 80% of affected
patients. This procedure is not as effective for women
taking birth control pills, pregnant women, or infants
younger than six months of age.
A second test involving an eye examination to
detect a characteristic ring of copper deposited in a
membrane of the cornea (referred to as KayserFleischer rings)is very easy to perform and is very
useful in diagnosing patients who have already exhibited symptoms. This test is not as effective in persons
without symptoms. This diagnostic test cannot be
used by itself to make a diagnosis because some
patients with liver disease but not Wilson disease will
test positive.
A third test for diagnosing Wilson disease
involves measuring the amount of copper in the liver.
This can be accomplished by sampling a portion of the
liver, called a biopsy. This is one of the most effective
ways in which to diagnose Wilson disease, however the
procedure itself is more difficult to perform than the
others.
GALE ENCYCLOPEDIA OF MEDICINE

Molecular genetic testing is not particularly valuable in diagnosing WD because of the large number of
possible gene mutations.

Finally, patients with Wilson disease are encouraged to follow a diet low in copper, with an average
copper intake of 1.0 mg/day. Foods to be avoided for
the high levels of copper include liver and shellfish.
Patients are also instructed to monitor their drinking
water for excess levels of copper and drink distilled
water instead.
Patients may be given a liver transplant in the
event of liver failure as a complication of WD. Liver
transplantation has been reported to have a relatively
favorable outcome, in some cases decreasing the
patient’s neurologic symptoms.

Prognosis



joint pain

Without treatment, Wilson disease is always fatal.
With treatment, symptoms may continue to worsen
for the first six to eight weeks. After this time, definite
improvement should begin to be seen. However, it
may take several years (two to five) of treatment to
reach maximal benefit to the brain and liver. Even
then, many patients are not returned to their original
level of functioning. Patients with Wilson disease need
to maintain some sort of anticopper treatment for the
rest of their lives in order to prevent copper levels from
rising in the body. Interruptions in treatment can
result in a relapse of the disease which is not reversible,
and can ultimately lead to death.



neurological problems

Resources



systemic lupus erythematosus

BOOKS



decreased production of all blood elements



interference with clotting



allergic reactions

Treatment
Treatment involves life-long administration of
either D-penicillamine (Cuprimine, Depen) or trientine hydrochloride (Syprine). Both of these drugs
remove copper deposits throughout the body by binding to the copper which then leaves the body in the
urine. This type of treatment is called chelation therapy. Zinc acetate (Galzin) and a low copper diet are
other ways in which to treat Wilson disease.
Penicillamine has a number of serious side effects:

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Mineral Deficiency and Toxicity.’’ In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2004.
PERIODICALS

Careful monitoring is necessary. When patients
have side effects from penicillamine, the dose can
sometimes be lowered to an effective level that causes
fewer difficulties. Alternatively, steroid medications
may be required to reduce certain sensitivity reactions.
Trientine has fewer potential side effects, but must still
be carefully monitored.
Treatment with zinc acetate is also an effective
way to remove excess copper from the body. Zinc is
a metal that works to block copper absorption and
bind copper in the intestinal cells until it is all released
into the stool approximately one week later. The benefit of treatment with zinc is there are no toxic side
effects however the zinc is a slower acting agent than
the other drugs. It takes four to eight months for the
zinc to be effective in reducing the overall amount of
copper in the body.
GALE ENCYCLOPEDIA OF MEDICINE

Carter, Beth A., MD. ‘‘Wilson Disease.’’ eMedicine June 17,
2004. <http://www.emedicine.com/ped/
topic2441.htm>.
Daniel, K. G., R. H. Harbach, W. C. Guida, and Q. P. Dou.
‘‘Copper Storage Diseases: Menkes, Wilsons, and Cancer.’’
Frontiers in Bioscience 9 (September 1, 2004): 2652–2662.
Georghe, L., I. Popescu, S. Iacob, et al. ‘‘Wilson’s Disease: A
Challenge of Diagnosis. The 5-Year Experience of a
Tertiary Centre.’’ Romanian Journal of
Gastroenterology 13 (September 2004): 179–185.
Gow, P.J., et al. ‘‘Diagnosis of Wilson’s Disease: AnExperience
Over Three Decades.’’ Gut 46 (March 2000): 415–419.
Robertson, W.M. ‘‘Wilson’s Disease.’’Archives of Neurology
57, no. 2 (February 2000): 276–277.
Velez-Pardo, C., M. J. Rio, S. Moreno, et al. ‘‘New
Mutation (T1232P) of the ATP-7B Gene Associated
with Neurologic and Neuropsychiatric Dominance
Onset of Wilson’s Disease in Three Unrelated
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Wilson disease

Other tests are also useful, for example measuring
the amount of copper passed into the urine daily (high
in Wilson disease). Another lab test measures the ability of a patient’s ceruloplasmin to bind with a form of
copper (decreased in Wilson disease). And finally, as
discussed under genetic profile, some patients can be
diagnosed through a DNA test to determine whether
or not they carry two genes for Wilson disease. This
test does not always prove to be useful in certain
patients and is of most use when used to test the
brothers and sisters of affected patients.

Wiskott-Aldrich syndrome

KEY TERMS
Anemia—A blood condition in which the level of
hemoglobin or the number of red blood cells falls
below normal values. Common symptoms include
paleness, fatigue, and shortness of breath.
Bile—A substance produced by the liver, and concentrated and stored in the gallbladder. Bile contains
a number of different substances, including bile salts,
cholesterol, and bilirubin.
Biopsy—The surgical removal and microscopic
examination of living tissue for diagnostic purposes.
Cell—The smallest living units of the body which
group together to form tissues and help the body
perform specific functions.
Ceruloplasmin—A protein circulating in the bloodstream that binds with copper and transports it.
Chelation therapy—A method of removing copper or
other heavy metals from the body by giving medications that bind to the metal and allow it to be excreted.
Chromosome—A microscopic thread-like structure
found within each cell of the body and consists of a
complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Changes in either the
total number of chromosomes or their shape and size
(structure) may lead to physical or mental abnormalities.
Cirrhosis—A chronic degenerative disease of the
liver, in which normal cells are replaced by fibrous
tissue. Cirrhosis is a major risk factor for the later
development of liver cancer.

Colombian Kindred.’’ Neuroscience Letters 367
(September 9, 2004): 360–364.
ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar
Grove, NJ 07009. (800) 223-0179. <http://
www.liverfoundation.org>.
National Organization for Rare Disorders (NORD). 55
Kenosia Avenue, P. O. Box 1968, Danbury, CT 068131968. (203) 744-0100. Fax: (203) 798-2291. <http://
www.rarediseases.org>.
Wilson’s Disease Association. 4 Navaho Dr., Brookfield,
CT 06804. (800) 399-0266.
OTHER

Wilson’s Disease Association. <http://www.medhelp.org/
wda/wil.htm>.

Katherine S. Hunt, MS
Rebecca J. Frey, PhD
4000

Deoxyribonucleic acid (DNA)—The genetic material in cells that holds the inherited instructions for
growth, development, and cellular functioning.
Gallbladder—A small, pear-shaped organ in the
upper right hand corner of the abdomen. It is
connected by a series of ducts (tube-like channels)
to the liver, pancreas, and duodenum (first part of
the small intestine). The gallbladder receives bile
from the liver, and concentrates and stores it. After
a meal, bile is squeezed out of the gallbladder
into the intestine, where it aids in digestion of
food.
Gene—A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence
found on a section of DNA. Each gene is found on a
precise location on a chromosome.
Glucose—One of the two simple sugars, together
with galactose, that makes up the protein, lactose,
found in milk. Glucose is the form of sugar that is
usable by the body to generate energy.
Hepatitis—A viral disease characterized by inflammation of the liver cells (hepatocytes). People
infected with hepatitis B or hepatitis C virus are at
an increased risk for developing liver cancer.
Jaundice—Yellowing of the skin or eyes due to
excess of bilirubin in the blood.
Toxic—Poisoinous.

Wiskott-Aldrich syndrome
Definition
Wiskott-Aldrich syndrome (WAS) is a rare inherited disorder marked by a low level of blood platelets,
eczema, recurrent infections, and a high risk of leukemia or lymph node tumors.

Description
WAS was named for the two physicians who first
reported the disorder. In 1937, Dr. A. Wiskott, a physician working in Munich, described two affected boys of
German ancestry who had repeated infections, a skin
rash, and poor blood-clotting ability.. Nearly twenty
years later, Dr. R.A. Aldrich reported similar symptoms
in members of an American family of Dutch ancestry.
GALE ENCYCLOPEDIA OF MEDICINE

Researchers identified the gene for WAS in 1994
and pinpointed its location on the short arm of the
X chromosome. As of 2000, over 100 different mutations have been found in the gene among WAS
patients. The fact that there are many mutations
many explain some of the variability of symptoms
among boys with WAS. However, even within the
same family, affected individuals with the identical
WAS gene mutation may have different degrees of
severity of the disease. The mild form, X-linked thrombocytopenia, is also caused by mutations in this
same gene.
The WAS syndrome affects one in every 250,000
male children and occurs worldwide. In the year 2000,
scientists estimated that about 500 Americans have
WAS.

Causes and symptoms
The syndrome is caused by a defect (mutation) in
a specific gene called the WAS gene that normally
codes for the protein named Wiskott-Aldrich
Syndrome Protein (WASP). This vital protein is a
component of cells that are important in the body’s
defense against infection (lymphocytes). The same
protein also functions in the cells that help prevent
bleeding (platelets). A less severe form of the disease,
X-linked thrombocytopenia affects mainly the
platelets.
Increased susceptibility to infections, eczema, and
excessive bleeding are the hallmarks of WAS,
although the symptoms can vary signficantly from
one patient to another. The immune system of patients
with WAS produces too few B and T cells. B cells are
GALE ENCYCLOPEDIA OF MEDICINE

the cells in the body that make antibodies. There are
many types of T cells. Both B and T cells are needed to
defend the body against infection. Because both types
of cells are affected, WAS patients are subject to
repeated infections from bacteria, fungi, and viruses.
Ear infections, meningitis, and pneumonia are common
in boys with WAS.
WAS patients also have thrombocytopenia, a
decreased number of platelets. Platelets are the specialized blood cells that help to form blood clots and
prevent uncontrolled bleeding. The platelets may
also be smaller than normal. Some of the earliest
symptoms of the syndrome are hemorrhage from
circumcision, bloody diarrhea, and a tendency to
bruise very easily.
Anemia and an enlarged spleen (splenomegaly)
are seen in some patients. About 10% of patients
develop malignancies, usually leukemia or tumors in
the lymph nodes (non-Hodgkin’s lymphoma).

Diagnosis
The diagnosis of WAS is usually suspected in male
infants who have excessive bleeding, eczema, and frequent bacterial or viral infections. Special blood tests
can then be ordered to confirm WAS. The blood of
Wiskott-Aldrich patients will show a low platelet
count and a weak immune (antibody) response. It is
also possible to confirm the diagnosis by obtaining a
small sample of the patient’s blood and analyzing the
DNA for a mutation in the WAS gene. Knowledge of
the exact mutation combined with information about
how much WAS protein the defective gene can produce may help predict how severe a form of the disease
an individual will have.
Carrier Testing
If the specific WAS gene mutation is identified in
an affected child, that child’s mother can then be
tested to confirm that she carries the gene. Other
members of the mother’s family may also want to
consider testing to find out if they carry the same
gene mutation. The first step in studying other family
members is for a geneticist or genetic counselor to
obtain a detailed family history and construct a pedigree (family tree) to determine which family members
should be offered testing.
Prenatal Diagnosis
In families where there has been one child born
with WAS, prenatal testing should be offered in subsequent pregnancies. There 50% chance with each
4001

Wiskott-Aldrich syndrome

WAS is inherited as an X-linked genetic disorder
and will therefore only affect males. The gene responsible for WAS is located on the short arm of the
X chromosome. Since males have only one X
chromosome they only have one copy of the gene. If
that copy carries the abnormal gene, they will have
WAS. In contrast, females have two X chromosomes.
They will have a normal copy of the gene on one
chromosome even if an abnormal gene is on the
other because the abnormal gene is very rare. The
normal copy on one X chromosome is usually sufficient to prevent females from having WAS. However,
women who have one abnormal copy of the WAS gene
are designated as carriers. While they will not have
WAS, they have a 50% risk of passing the gene to each
of their sons who will have WAS. Carrier females also
have a 50% risk of passing the defective copy of the
gene to their daughters who also become carriers.

Wiskott-Aldrich syndrome

KEY TERMS
Amniocentesis—A procedure performed at 16-18
weeks of pregnancy in which a needle is inserted
through a woman’s abdomen into her uterus to draw
out a small sample of the amniotic fluid from around
the baby. Either the fluid itself or cells from the fluid
can be used for a variety of tests to obtain information about genetic disorders and other medical conditions in the fetus.
Anemia—A blood condition in which the level of
hemoglobin or the number of red blood cells falls
below normal values. Common symptoms include
paleness, fatigue, and shortness of breath.
Chorionic villus biopsy—A procedure used for prenatal diagnosis at 10-12 weeks gestation. Under
ultrasound guidance a needle is inserted either
through the mother’s vagina or abdominal wall and
a sample of cells is collected from around the early
embryo. These cells are then tested for chromosome
abnormalities or other genetic diseases.
Eczema—Inflammation of the skin with redness and
other variable signs such as crusts, watery discharge,
itching.
Gene—A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence

subsequent pregnancy that the mother, who is a carrier, will transmit the abnormal copy of the gene to her
baby. The key is to first identify the particular WAS
gene mutation in the child with WAS. Then, early in a
pregnancy, cells can be obtained from the developing
fetus by chorionic villus sampling or amniocentesis, and
checked for the same mutation. Women who carry the
abnormal WAS gene and are considering prenatal
diagnosis should discuss the risks and benefits of this
type of testing with a geneticist or genetic counselor.

Treatment
Standard treatments for individuals with WAS
include antibiotics for infections and platelet transfusions to limit bleeding. Immune globulin is given to
strengthen the individual’s immune system. Eczema
can be treated with corticosteroid creams applied
directly to the skin. The spleen is sometimes removed
to reduce the risk of bleeding. In individuals with WAS,
however, removal of the spleen also increases the risk
of infection unless antibiotics are given to prevent
4002

found on a section of DNA. Each gene is found on a
precise location on a chromosome.
Immune system—A major system of the body that
produces specialized cells and substances that interact with and destroy foreign antigens that invade the
body.
Mutation—A permanent change in the genetic
material that may alter a trait or characteristic of an
individual, or manifest as disease, and can be transmitted to offspring.
Platelets—Small disc-shaped structures that circulate
in the blood stream and participate in blood clotting.
Prenatal diagnosis—The determination of whether a
fetus possesses a disease or disorder while it is still in
the womb.
Syndrome—A group of signs and symptoms that
collectively characterize a disease or disorder.
Thrombocytopenia—A persistent decrease in the
number of blood platelets usually associated with
hemorrhaging.
X-linked—Located on the X chromosome, one of the
sex chromosomes. X-linked genes follow a characteristic pattern of inheritance from one generation to
the next.

infections. About 50% of individuals with WAS are
helped by treatment with transfer factor, which is a
substance derived from the T cells of a healthy person.
Transfer factor is given to improve both blood clotting
and immune functions. Bone marrow transplantation
has been successful in a number of cases. It has been
most successful in boys under five years of age where
the donor is a sibling whose tissue type closely matches
that of the individual with WAS. As of 2000, attempts
were also being made to treat individuals with WAS
with umbilical cord blood from unrelated newborns in
cases where the individual diagnosed with WAS has no
matched sibling donor.

Prognosis
The prognosis for males diagnosed with WiskottAdrich syndrome is poor. The average individual lives
about four years; those who survive into adolescence
often develop cancer. Death usually occurs from severe
bleeding or overwhelming infection in the first few
years of life.
GALE ENCYCLOPEDIA OF MEDICINE

level of an inhibitory neurotransmitter, GABA, therefore it serves as a tranquilizer.)

BOOKS

Belmont, J. W., and J. M. Puck. ‘‘T Cell and Combined
Immunodeficiency Disorders.’’ In The Metabolic &
Molecular Bases of InheritedDisease, edited by C. R.
Scriver, et al. New York: McGraw-Hill, 2001.
PERIODICALS

Kuska, B. ‘‘Wiskott-Aldrich Syndrome: Molecular Pieces
SlideInto Place.’’ Journal of the National Cancer
Institute 92 (January 5, 2000): 9-11.
ORGANIZATIONS

Immune Deficiency Foundation. 25 W. Chesapeake Ave.,
Suite 206, Towson, MD 21204. (800) 296-4433.
<http://www.primaryimmune.org/inside.htm>.
OTHER

‘‘Entry 301000: Wiskott-Aldrich Syndrome.’’ OMIM—
Online Mendelian Inheritance in Man. <http://
www.ncbi.nlm.nih.gov/entrez/
dispomim.cgi?id=301000>.
NORD—National Organization for Rare Disorders, Inc.
<http://www.rarediseases.org>.

Sallie Boineau Freeman, PhD

Withdrawal syndromes
Definition
Withdrawal syndrome occurs in drug and alcohol
addicted individuals who discontinue or reduce the use
of their drug of choice. This process of eliminating
drugs and alcohol from the body is known as detoxification. Anxiety, insomnia, nausea, perspiration,
body aches, and tremors are just a few of the physical
and psychological symptoms of drug and alcohol
withdrawal that may occur during detoxification.

Description
Drugs and alcohol affect mood by altering brain
chemistry, specifically the production of neurotransmitters. Neurotransmitters are chemicals in the central
nervous system that enable nerve impulses to travel
through the central nervous system and regulate
thought processes, behavior, and emotion. Drugs
that temporarily elevate neurotransmitter levels are
called stimulants. Drugs that decrease neurotransmitter levels and depress the central nervous system are
called depressants; they include opiates and sedativehypnotic drugs such as alcohol and barbiturates.
(There are exceptions: Benzodiazepine elevates the
GALE ENCYCLOPEDIA OF MEDICINE

When drug or alcohol consumption becomes
chronic, the body adjusts to the constant presence of
the substance by changing its normal production of
neurotransmitters. If drug and alcohol use suddenly
stops, the body and central nervous system react to the
absence of the substance with an array of symptoms
known collectively as withdrawal syndrome.

Causes and symptoms
Acute withdrawal syndrome begins within hours
of abstinence, and includes a full range of physical and
psychological symptoms. More long-term, or subacute, withdrawal symptoms, such as intense drug craving, may occur weeks or months after detoxification
has taken place.
Alcohol withdrawal
Alcohol withdrawal syndrome occurs in alcoholdependent individuals who suddenly stop or dramatically reduce their alcohol intake. The onset of the
syndrome is likely to occur within a week, but usually
occurs within 24 hours of the individual’s last drink,
and is triggered when the central nervous system
attempts to adjust to the sudden absence of ethyl
alcohol in the body. Symptoms may include extreme
anxiety, disorientation, hallucinations, sleep disorders,
hand tremors, nausea, sweating, seizures, and racing
pulse. Delirium tremens (DTs) are an extreme example
of withdrawal. In the worst cases, untreated alcohol
withdrawal syndrome can result in death. As many as
two million Americans may experience symptoms of
alcohol withdrawal conditions each year.
Barbiturate withdrawal
Barbiturates are prescribed as anticonvulsants,
sedatives, and general anesthetics. They can also
mimic some of the characteristics of alcohol intoxication (including euphoria, elation, and uninhibited
behavior), which make them candidates for abuse.
Commonly abused barbiturates include amobarbital
(Amytal), pentobarbital (Nembutal), and secobarbital
(Seconal). These drugs depress the respiratory and
nervous system functions. Because abusers rapidly
build up a tolerance to the effects of the drug, fatal
overdose or coma can easily occur. Symptoms of withdrawal syndrome appear 12-20 hours after the last
dose; they include anxiety, irritability, elevated heart
and respiration rate, muscle pain, nausea, tremors,
hallucinations, confusion, and seizures. Death is a
4003

Withdrawal syndromes

Resources

Withdrawal syndromes

possibility if the condition is left untreated. Because
barbiturates decrease REM (rapid eye movement)
sleep, during which dreaming takes place, withdrawal
often results in sleep disruptions such as nightmares,
insomnia, or vivid dreaming.
Opiate withdrawal
Opiates are powerfully addictive analgesic drugs
that deaden nerve pathways related to pain. Abusers
of propoxyphene (Darvon), meperidine (Demerol),
percocet (Oxycodone), heroin, morphine, and other
powerfully addictive opiates quickly build up a tolerance to the drugs and need progressively larger doses
to achieve the desired effect. Stopping or reducing the
intake of the drug can cause severe withdrawal symptoms, which begin six to eight hours after the last
dosage. Symptoms are flu-like, and include gastrointestinal distress, anxiety, nausea, insomnia, muscle
pain, fevers, sweating, and runny nose and eyes.
Stimulant withdrawal
Use of stimulants, such as cocaine, crack, amphetamines, and methamphetamines, cause an increase in
neurotransmitters in the central nervous system and
produce feelings of alertness and increased energy.
This initial ‘‘rush’’ is followed by a longer period of
neurotransmitter loss, characterized by depression,
lethargy, and a craving for more stimulants sometimes
called a rebound effect. When a stimulant-dependent
individual abstains from stimulant use, withdrawal
symptoms, including depression, fatigue, insomnia,
and loss of appetite, reflect this drop in neurotransmitter levels. Withdrawal typically takes one to two
weeks.

Diagnosis
A detailed history of the patient’s drug or alcohol
use taken before detoxification can be helpful in predicting the severity of withdrawal symptoms.
Standardized clinical tests, such as the Clinical
Institute Withdrawal Assessment for Alcohol, revised,
(CIWA-Ar), are used to evaluate the severity of withdrawal symptoms throughout the detoxification
procedure.

Treatment
Pharmacologic and medical management is often
recommended for withdrawal syndrome. The physical
condition of the patient is closely monitored throughout the detoxification procedure.
4004

Alcohol withdrawal
Alcohol withdrawal syndrome can be treated at
home or in a hospital or treatment setting. Inpatient
treatment is recommended for patients who are at risk
for serious withdrawal symptoms or re-intoxication if
treated as an outpatient. Withdrawal symptoms are
minimized through the administration of cross-tolerant sedatives. Long-acting benzodiazepines, such as
diazepam (Valium), chlordiazepoxide (Librium), and
lorazepam (Ativan), are the pharmacologic treatments
of choice in managing the symptoms of alcohol withdrawal. Drug dosage is adjusted to offset the discomfort of withdrawal, without causing a euphoric effect,
and is then gradually decreased as withdrawal symptoms lessen.
Barbiturate withdrawal
Because the risk for seizures and other severe
complications is high, barbiturate withdrawal should
be monitored in a hospital setting. Patients are given
low doses of phenobarbital at a regular interval until
mild intoxication is achieved. The dosage amount and
frequency is then gradually decreased until withdrawal
is complete.
Opiate withdrawal
Two basic treatment approaches are used for
managing opiate withdrawal. The first involves treating the symptoms of the withdrawal with appropriate
medication. Clondine, an antihypertensive drug, is
commonly prescribed to reduce muscle pain and
cramping. Other symptom-specific drugs are administered on an as-needed basis.
The second treatment option is to replace the
patient’s drug of choice with methadone, a long-acting,
cross-tolerant opiate that does not normally produce a
‘‘high.’’ Doses of methadone are administered every
four to six hours. The patient’s reaction is closely
observed, and dosages are slowly decreased until withdrawal symptoms have disappeared, then dosages are
discontinued. Methadone withdrawal can be completed
within three weeks. It is important to note that methadone withdrawal treatment differs from a methadone
maintenance program, in which patients who are
unwilling to give up opiates are prescribed methadone
as a legal, long-term substitute for their drug of choice.
Rapid opiate detoxification (ROD) is an emerging
treatment option for opiate withdrawal. The ROD
method is reported to be faster and to cause less physical discomfort than traditional forms of opiate
detoxification. The treatment is typically performed
in a hospital or private clinic setting. Naltrexone, an
GALE ENCYCLOPEDIA OF MEDICINE

Analgesics—Pain killing drugs that depress respiratory function. Opiates are analgesics.
Antagonist—A substance that tends to nullify the
action of another.
Benzodiazepines—Sedatives used to treat anxiety,
epilepsy, and alcohol withdrawal syndrome.
Diazepam (Valium), alprazolam (Xanax), and chlordiazepoxide (Librium) are all benzodiazepines.
Cross-tolerant—A drug that has the same pharmacological effect as another is considered crosstolerant. Cross-tolerant drugs are often used in
treating withdrawal syndromes.
Detoxification—The process of physically eliminating drugs and/or alcohol from the system of a
substance-dependent individual.
Dysphoria—A depressed and anxious mood state.
Neurotransmitters—Chemicals in the brain that
affect the nervous system and alter thinking
patterns.
Opiates—Analgesic, pain killing drugs, such as
heroin and morphine that depress the central nervous system.

opiate antagonist that blocks opiate receptors and
reverses the effects of opiates, is administered to trigger the withdrawal response. Clonidine is given simultaneously to ease the symptoms of withdrawal. The
patient is anesthetized throughout the three to four
hour procedure, and withdrawal occurs while the
patient sleeps. Vital signs are monitored closely and a
ventilator may be employed.

withdrawal experience for the patient. Detoxification
is only a short-term solution for obtaining abstinence.
An addiction treatment and long-term recovery program is necessary to achieve long-term sobriety.
Without such a treatment program, the likelihood of
recurrence of abuse and, therefore, the recurrence of
withdrawal syndrome is high.

Prevention
After detoxification, alcohol and drug dependent
individuals are encouraged to maintain their abstinence through participation in substance abuse treatment or a twelve-step recovery program.
Resources
PERIODICALS

Bayard, Max, et al. ‘‘Alcohol Withdrawal Syndrome.’’
American Family Physician March 15, 2004: 1443.
‘‘Single Injection May Relieve Opiate Withdrawal.’’
Alcoholism & Drug Abuse Weekly January 19, 2004: 8.
ORGANIZATIONS

Alcoholics Anonymous. General Service Office. 475
Riverside Drive, New York, NY 10015. (212) 870-3400.
<http://www.alcoholics-anonymous.org>.
National Clearinghouse for Alcohol and Drug Information.
Center for Substance Abuse Prevention. P.O. Box 2345,
Rockville, MD 20847-2345. (800) 729-6686. <http://
www.health.org>.
National Council on Alcoholism and Drug Dependence. 12
West 21st St., New York, NY 10010. (800) 622-2255.
<http://www.ncadd.org>.
National Institute on Alcohol Abuse and Alcoholism
(NIAAA). 6000 Executive Boulevard, Willco Building,
Bethesda, Maryland 20892-7003. <http://
www.niaaa.nih.gov>.

Paula Anne Ford-Martin
Teresa G. Odle

In early 2004, a new single injection method for
opiate addiction was being tested. It consisted of a
slow-release form of buprenorphine and prevented
symptoms for an entire month.
Stimulant withdrawal
Because of the depression and dysphoria (feeling
of a psychological low) related to stimulant withdrawal, psychological and/or medical management is critical. Treatment may include a regimen of drugs that
increase neurotransmitter production.

Prognosis
A closely observed, medically managed detoxification typically results in a safe and tolerable
GALE ENCYCLOPEDIA OF MEDICINE

Wolff-Parkinson-White
syndrome
Definition
Wolff-Parkinson-White syndrome is an abnormality in the electrical functioning of the heart which
may cause rapid heart rates. The abnormality affects
the electrical signal between the atria and ventricles.
4005

Wolff-Parkinson-White syndrome

KEY TERMS

Wolff-Parkinson-White syndrome

Description
Blood is circulated through the heart and body by
a muscular pump and valve system involving the atria
and ventricles. The right atrium receives oxygen-lacking blood returning to the heart from the body. The
blood is passed from the right atrium into the right
ventricle, which contracts and sends blood out to the
pulmonary artery. The pulmonary artery sends the
blood into the lungs, where carbon dioxide is removed,
and fresh oxygen is added. The left atrium receives
blood with oxygen from the lungs and passes this
arterial blood to the left ventricle, where it is emptied
into the aorta, the main artery of the heart.
These functions are directed by electrical signals
within the heart. In patients afflicted with WolffParkinson-White syndrome, an abnormal pathway
exists that causes additional electrical signals to pass
between the atria and ventricles, possibly causing
rapid heart rate.

Causes and symptoms
Congenital heart disease may contribute to this and
other arrhythmias. Ebstein’s anomaly, a congenital
heart defect that involves displacement of the tricuspid
valve, located on the right side of the heart, is one
known cause of Wolff-Parkinson-White syndrome.
This anomaly allows blood to flow via the small hole
to the other side of the heart. Often, there is no known
cause for Wolff-Parkinson-White syndrome. Many
people with the syndrome have no symptoms. On the
other hand, some people experience temporary rapid
heartbeat due to certain drugs, smoking, and anxiety.

Diagnosis
Electrocardiography (ECG) is used to diagnose
Wolff-Parkinson-White syndrome, and other cardiac
arrhythmias. A trained physician, normally a cardiologist, can recognize patterns of electrical conduction.
With this syndrome, the extra pathway will show a
pattern different from those of normal conduction. If
no irregular patterns show on the ECG, the patient
may be sent home with a 24-hour heart monitor, called
a Holter monitor, which will help detect intermittent
occurrences. Other studies, such as the cardiac electrophysiologic study (EPS), may be ordered to pinpoint
the location of the accessory pathway, and to determine a course of treatment.

Treatment
Various drugs may be used to treat WolffParkinson-White syndrome, as well as other cardiac
4006

KEY TERMS
Ablative—Used to describe a procedure involving
removal of a tissue or body part, or destruction of its
funtion.
Arrhythmia—Irregular heart beat.
Electrocardiograph (ECG)—A test of a patient’s
heartbeat that involves placing leads, or detectors,
on the patient’s chest to record electrical impulses
in the heart. The test will produce a strip, or picture
record of the heart’s electrical function.
Tachycardia—Rapid heart rate, defined as more
than 100 beats per minute.

arrhythmias. The purpose of these drugs is to slow the
electrical signals and excitation of heart muscles. As
some of these drugs may have side effects, including
the rare production of new or more frequent arrhythmias, the patient should be carefully observed.
Ablative therapies may be accomplished with radiofrequency or cardiac catheters to cut through the tissue which is causing the abnormal electrical signals.
At one time, only open heart surgery was used,
but the procedure can be done now with local anesthesia in a special cardiac laboratory. In some cases,
surgery may still be recommended to treat WolffParkinson-White syndrome.Young people with this
syndrome may be treated more successfully with surgery, rather than enduring a lifetime of drug treatments, or the possible threat of sudden cardiac death.

Alternative treatment
A provider may teach patients methods to help
control heart rate. Relaxation techniques, acupuncture, botanical medicine, and homeopathy can all be
helpful supportive therapies.

Prognosis
Most patients with this syndrome can lead normal
lives, even with episodes of tachycardia. In many
cases, the syndrome is secondary to the underlying
congenital heart defect. However, Wolff-ParkinsonWhite syndrome can cause sudden cardiac arrest in
certain instances.

Prevention
If the syndrome is not due to congenital heart
disease, the patient may try avoiding behaviors
GALE ENCYCLOPEDIA OF MEDICINE

Resources
ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas,
TX 75231. (214) 373-6300 or (800) 242-8721. inquire@heart.org<http://www.americanheart.org>.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://
www.nhlbi.nih.gov>.

Teresa Odle

Women’s health
Definition
Women’s health is the effect of gender on disease
and health that encompasses a broad range of biological and psychosocial issues.

Description
Women’s health is the concept that examines gender differences in health and disease states. The average life expectancy has almost doubled for women (79
years for women and 73 years for men), when compared with averages during the turn of the century.
Because of the gender gap in lifespan, women comprise approximately two thirds of the population older
than 65 and three fourths of the population aged 85
years and older. Currently the fastest growing group in
the United States is persons aged 85 years and older.
Because of gender life expectancy differences, it is
estimated that at the beginning of the twenty-first
century, women will outnumber men in the 85 years
and older category by 3:1. The reasons for this variance are primarily due to physiological differences
among men and women.
During different phases of a women’s life cycle
there are complex interactions that exist between sex
hormones, physiological changes, and emotional
issues. Physiological changes occur as early as
embryonic development when hormones program
structural differences between male and female brains.
During reproductive years, sex hormones profoundly
influence reproduction and development, which creates a spectrum of gender specific health issues. With
advancing age and onset of menopause, women’s risk
factors for disease is comparably similar to men’s.
GALE ENCYCLOPEDIA OF MEDICINE

Although the same disease may affect women as
men, it is thought that biological mechanisms and
psychosocial differences influence the clinical course
of the disease (natural history) differently in women.
The number of women working has doubled within
the past 50 years. The effect of work stress, new environmental exposures and multiple roles is expected to
have health and social impact.
The leading causes of death among women are
cardiovascular disease, malignant cancer, cerebrovascular disease, chronic lung disease, pneumonia/influenza, and diabetes. Additionally, women can be prone
to osteoporosis, alcohol abuse, psychological disorders, human immunodeficiency virus infection, and
violence.
Heart Disease accounts for approximately a third
of all deaths in women. About 250,000 women die
annually of coronary heart disease or a one in three
chance after age 40 years. The incidence of heart disease occurs about 10 years later in women than in men,
since estrogens in premenopausal women has a protective effect. African American women are more
prone to die from heart disease up to age 75. Beyond
75 years of age the propensity is reversed. Native
American and Hispanic women have lower death
rates from heart disease.
Malignant cancers are the most common cause of
premature death among women. Breast cancer is the
second leading cause of death in women and the most
commonly diagnosed cancer. Lung cancer, secondary
to cigarette smoking is the leading cause of cancer
death among women.
Cerebrovascular disease, or stroked related deaths
account for approximately 6% of all deaths in women
and it is the third leading cause of mortality. The least
common form of stroke, subarachnoid hemorrhage, is
the more common cause in women.
The prevalence of cigarette smoking has increased
greatly in women and this is correlated with pulmonary disease. Death rates for pulmonary disease including cancer and infectious causes of death are expected
to rise for women.
Diabetes, a leading cause of death in women is
more prevalent among Hispanic, African American,
and Native American women. Past age 45, diabetes
affects about one in six women.
Women can also develop:


osteoporosis, or loss of the quantity of bone, common
in postmenopausal women who have estrogen
changes.
4007

Women’s health

which lead to arrhythmia, such as elimination of caffeine, alcohol, cocaine, and smoking.

Women’s health



alcohol abuse, characterized by repeated usage of
alcohol despite negative consequences. These
women frequently do not seek treatment because of
fear of consequences (i.e., loss of child custody). This
disease can also have adverse affects on fertility and
in the developing fetus if the mother continues to
consume alcohol (fetal alcohol syndrome).



psychological disorders, such as depression and eating disorders.



acquired immunodeficiency syndrome (AIDS), which
represents the highest percent increase in death rates.



violence, a leading cause of death, primarily caused
by a perpetrator who is or was a partner.

Causes and symptoms
Cardiovascular disease can be caused by blockage
of a blood vessel, high blood pressure, or a secondary
complication to another disease. There may be an
abnormal heart rhythm or cell death. Patients may
complain of a broad spectrum of symptoms that may
include pain chest discomfort, high blood pressure, or
strain during physical exertion.
When attempting to define the cause and symptoms of cancer, it is important to assess the type of
cancer and location. Additionally, if the tumor is localized (benign) or has spread to other areas (malignant),
is vital for treatment planning and overall prognosis.
In cases of breast cancer there mat be a lump discovered during self-examination or mammography (special breast x rays).
Cerebrovascular disease may cause tremors (shaking), loss of balance and coordination, or functional
and sensation loss of some parts of the body. Patients
may have sudden transient strokes that could result in
temporary loss of consciousness and amnesia of the
incident. Patients may also develop chronic neurological states that causing memory loss and behavioral
changes (Alzheimer’s disease).
Patients with pulmonary (lung) cancer may
develop shortness of breath, fatigue, weight loss, worsening cough, and coughing up bright red blood with
sputum. Lung infections such as pneumonia may present with high fever, weakness, difficulty breathing,
and abnormal breathe sounds heard with a stethoscope during physical examination.
Diabetes is a syndrome with disordered metabolism and high blood sugar due to an abnormality in the
chemical that regulates sugar levels. It is characterized
by an increased thirst, urination, and chronic skin
infections.
4008

Osteoporosis may cause the bones to be brittle
and weak. It is usually not detected until bones start
to break.
The alcohol abuser will continue to drink despite
negative repercussions. The person may not seek treatment to evade legal and/or child custody problems.
The patient may hide alcohol, or confine drinking to
specific times. The disease progresses to where there
may be permanent liver damage, memory blackouts
and malnutrition.
Depression may manifest a loss of interest and
desire. Patients may have difficulty getting out of
bed. They may lack motivation to work or tend to
daily activities.
Patients with AIDS may not have symptoms for
years. When active disease occurs, patients will typically develop recurrent infections that are the usual
cause of death.
Domestic violence is usually associated with a
perpetrator who is in a relationship with the affected
person. Abuse can be manifested by physical violence
and/or homicide.

Diagnosis
Diagnosis can be accomplished with a history,
physical examination, and specialized tests or procedures. For cardiovascular disease an electrocardiogram
can determine the activity of the heart. Additional tests
may include echocardiography (ultrasonic waves that
generate an image), stress testing, and studies that
require placing a catheter with a probe to examine the
damage to heart tissue. Special tests with dyes may also
be injected to enhance visualization. Cancer may be
detected using specialized test called tumor makers
and imaging studies such as MRI and CAT scans.
Cerebrovascular disease can be detected with a complete neurological examination and specialized imaging
technology. Diabetes is usually detected by a careful
history presence of risk factors (obesity) and blood
analysis of glucose levels. Osteoporosis can be evaluated with specialized bone densitometry. Alcohol abuse
can be established by a bio-psycho-social assessment
and standardized tests which screen for this disorder.
Psychological evaluation (such as the Minnesota
Multiphasic Personality Inventory, MMPI) can usually
detect depression or eating disorders. AIDS can be
established by a careful history, belonging to high-risk
groups and Western blot analysis (examination of
blood to detect the protein of human immunodeficiency virus). Violence can be established by physical
signs of beating, such as cuts and bruises.
GALE ENCYCLOPEDIA OF MEDICINE

Treatment depends on the extent of disease and
the present health status of the patient. Additionally,
in some cases treatment may stopped at sometime, or
it may altogether be refused. Treatment for cardiovascular disease may include surgical intervention
and/or conservative medical treatment with medications. Diet, exercise, and weight reduction are important parameters for treatment planning. Appropriate
referrals, counseling, and follow up are usually indicated. Treatment for cancer may include a combination of surgery, chemotherapy or radiation therapy.
These treatment modalities may be given singly or in
combination or at different times during disease progression. Cerebrovascular disease can be treated surgically and/or with medications that thin the blood.
Symptomatic care may be indicated in addition to
close monitoring if the patient develops disability
and/or cognitive impairment. Diabetes can be treated by dietary modifications and medications, which
treat abnormal levels of blood glucose (sugar).
Osteoporosis can be treatment with estrogen replacement and regular vitamin/mineral intake. Alcohol
abuse may require long-term therapy, inpatient treatment and medications. Community centered support
group meeting are also recommended as a form of
treatment maintenance. To date there is no treatment for AIDS, other than medications, that offer
symptomatic relief. Alcohol abuse, psychological disorders and violence require therapy, possible medication, and community centered support group
meetings.

KEY TERMS
Electrocardiogram— An instrument that monitors
heart rate and rhythm.

Prevention
One of the most reliable measures of prevention is
education and training. The Council on Graduate
Medical Education has provided funding for numerous
centers to research women health issues. On more individual level preventive and personal habits are vital for
good health. Most physicians believe that a baseline
physical examination is a reliable comparative tool.
Women should receive counseling for special issues
concerning cigarette smoking, exercise, diet, primary
disease prevention, safe sexual practices, alcohol
abuse, psychological disorders, and violence.
Additionally, knowledge of family history is important
since many diseases have a strong propensity among
first-degree relatives. Blood pressure should normally
be measured every other year. Screening tests for
breast, cervical, and colorectal cancer is recommended.
Pap smears taken during routine pelvic examinations
can screen for disease processes in the reproductive
tract. Serum cholesterol monitoring and reduction are
advised. Patients may require postmenopausal estrogen
replacement therapy and vitamin/mineral supplements.
Resources
BOOKS

Alternative treatment
There are numerous studies which support
intake of coenzyme Q10 for cardiovascular health.
Studies have shown that beta-carotene and vitamin
E and C have no effect for cancer. Some studies
indicate positive results for reproductive health
using acupuncture. Some advocates proposed certain herbs may be beneficial during menopause.
According to most medical literature, further
research using scientific method is vital for general
acceptance.

Ryan, Kenneth J., et al, editors. Kistner’s Gynecology &
Women’s Health. 7th ed. Mosby, Inc., 1999.
PERIODICALS

Lautenbach, G. L., and M. Petri. ‘‘Women’s Health:
GeneralMedical Care of the Patient with Rheumatic
Disease.’’ Rheumatic Diseases Clinics of NorthAmerica
25 (August 1999).

Laith Farid Gulli, M.D.
Bilal Nasser, M.Sc.

Prognosis
The prognosis depends on the extent of disease
and the physical and emotional status of the patient.
Prognosis is also related to tolerance of treatment,
adverse drug effects, and complication during or
after surgery, disease resurgence and patient compliance with treatment recommendations.
GALE ENCYCLOPEDIA OF MEDICINE

Wound culture
Definition
A wound culture is a laboratory test in which
microorganisms from a wound are grown in a special
4009

Wound culture

Treatment

Wound culture

growth medium. It is done to find and identify the
microorganism causing an infection in a wound or an
abscess. If a microorganism is found, more testing is
done to determine how to treat the infection.

Purpose
Wounds are injuries to body tissues caused by
disease processes or events such as burns, punctures,
and human or animal bites. Wounds or abscesses also
occur within body tissues as a result of surgery or
dental procedures. Wounds become infected when
microorganisms from the outside environment, or
from within the person’s body, enter the open wound
and multiply. A wound that is red, painful, swollen,
and draining pus is probably infected. A fever following surgery indicates an infection at the site of surgery.
To enable healing and prevent the spread of infection to other body tissues, the infecting microorganisms must be killed. A wound culture discovers which
type of microorganism is causing the infection and the
best antibiotic with which to kill it. This is important
as physicians have become less inclined to prescribe
antibiotics until certain they are needed because of
antibiotic resistance that has developed due to overuse
of the drugs.

Description
A sample of material, such as pus or a portion of
tissue, is taken from the wound, placed in a sterile
container, and sent to the laboratory. In the laboratory, this material is spread over the surface of several
different types of culture plates and placed in an incubator at body temperature for one to two days.
A Gram stain is done by staining the slide with
purple and red stains, then examining it under a microscope. If many white blood cells and bacteria are seen,
it is an early confirmation of infection. The color of
stain retained by the bacteria (purple or red), their
shape (such as round or rectangular), and their size
provides valuable clues as to their identity, and helps
the physician predict which antibiotics might work
best even before the entire test is completed. Bacteria
that stain purple are called gram-positive; those that
stain red are called gram-negative.
Bacteria can be grouped into two categories: aerobes and anaerobes. Aerobes are bacteria that need
oxygen to live; anaerobes live only where there is no
oxygen. Deep wounds, closed-off from oxygen, are an
ideal environment for an anaerobic infection to
develop. Foul-smelling odor, gas, or gangrene at the
infection site are signs of an infection caused by an
4010

anaerobic bacteria. Routine cultures typically only
look for aerobic bacteria. If the physician tells the
laboratory to include a culture for anaerobes, a portion of the wound sample will be put on culture plates,
or in a tube of culture broth, and incubated in a special
chamber without oxygen.
Bacteria present in the wound sample will multiply and appear as visible colonies on the plates, or as
cloudiness in the tube of broth. They are identified by
the appearance of their colonies, the results of biochemical tests, and information from Gram staining
part of the bacterial colony.
A sensitivity test, also called an antibiotic susceptibility test, is also done. The bacteria are tested against
different antibiotics to determine which will treat the
infection by killing the bacteria.
If the physician thinks the wound may be infected
with a mold or yeast, a fungal culture is also done. The
wound sample is spread on special culture plates that
are treated to encourage the growth of mold and yeast.
Different biochemical tests and stains are used to
identify molds and yeast.
Other more unusual microorganisms, such as
Mycobacterium leprae, may be the cause of a wound
infection. The physician must notify the laboratory to
culture specifically for these more unusual
microorganisms.
The initial Gram stain result is available the same
day, or in less than an hour if requested by the physician. An early report, known as a preliminary report,
is usually available after one day. This report will tell if
any microorganisms have yet been found, and, if so,
their Gram stain appearance. For example, they may
have the appearance of a gram-negative rod, or a
gram-positive cocci (spherical shape). The final report,
usually available in one to three days, includes complete identification, an estimate of the quantity of the
microorganisms, plus a list of the antibiotics to which
they are sensitive. Cultures for fungi and anaerobic
bacteria may take two to three weeks.
Wound culture is also called soft tissue culture,
abscess culture, or wound culture and sensitivity.

Preparation
A piece of the infected tissue is the best specimen.
If this is not possible, the next best specimen is pus
from the wound. Because many microorganisms normally live on skin and mucous membrane, the specimen must not be allowed to touch the area
surrounding the wound.
GALE ENCYCLOPEDIA OF MEDICINE

Aerobe—Bacteria that require oxygen to live.
Anaerobe—Bacteria that live only where there is
no oxygen.

Wound Healing Society. 1550 South Coast Highway, Suite
201, Laguna Beach, CA 92651. (888) 434-4234.
<http://wizard.pharm.wayne.edu/woundsoc/
WHS.HTM>.

Nancy J. Nordenson
Teresa G. Odle

Normal flora—The mixture of bacteria normally
found at specific body sites.

The physician first cleans the surface of the
wound using alcohol. Using a syringe, the physician
suctions out (aspirates) as much pus as possible from
the wound. Next, this is sent to the laboratory in a
sterile container. If it is impossible to aspirate the pus,
pus from within the wound can be collected on a
swab.
The physician may choose to start the person on
an antibiotic before the culture and sensitivity tests are
completed. However, the specimen for culture should
be collected before antibiotics are begun. Antibiotics
in the person’s system may prevent microorganisms
present in the wound from growing in culture, and
thus not be identifiable.

Normal results
A normal culture may be contaminated by a mixture of microorganisms normally found on a person’s
skin (normal flora).
It is not uncommon for the microorganism
causing a wound infection to not grow in culture.
This is particularly true if the specimen was collected with a swab rather than an aspirate or tissue
biopsy.

Abnormal results
Streptococcus Group A, Escherichia coli,
Proteus, Klebsiella, Pseudomonas, Enterobacter,
Enterococci, Staphylococcus aureus, Bacterioides,
and Clostridium, are common causes of wound infections. More than one microorganism may be the
cause of the infection.
Resources
PERIODICALS

‘‘Does Increased Use of Antibiotics Result in Increased
Antibiotics Resistance?’’ Clinical Infectious Diseases
July 1, 2004: 18–20.

GALE ENCYCLOPEDIA OF MEDICINE

Wound flushing
Definition
Wound flushing is a method of cleaning a wound
by applying pressurized water or antiseptic solutions
to the tissues. It is also called irrigation.

Purpose
Wound flushing is used to help flush debris from a
wound, lessening the risk of infection or treating an
infection that already exists. If the wound is flushed
with an antiseptic, it is more likely to heal correctly;
flushing the wound can help prevent the surface from
healing over a possibly infected area underneath.
Wound flushing is routinely performed by dentists or oral surgeons following tooth extractions,
mouth trauma, or gum surgery, to prevent bacteria
from the mouth entering the bloodstream as well as to
cleanse the tooth socket.

Description
Wound flushing is usually done in a hospital or
oral surgery center, though if it is performed at home,
there is less chance of infection because of the higher
risk of bacterial contamination in the hospital environment. Wound flushing is especially helpful in treating
people with bites, lacerations, or crush injuries, which
often become infected due to the presence of dead tissue
and foreign debris, such as splinters or dirt. In a nonsurgical situation, the procedure is usually performed
by a nurse. An acute injury, such as a crushing wound
or knife cut, the wound is flushed right before the injury
is stitched closed. For people with chronic wounds, such
as bed sores or abscesses, the wound may be flushed
periodically to treat or prevent infection. During an
operation, a surgeon uses an antibacterial solution to
flush the surgical site just before stitching the wound
closed. After surgery, the wounds may be flushed to
treat or prevent infection.
4011

Wound flushing

ORGANIZATIONS

KEY TERMS

Wounds

KEY TERMS
Antiseptic—Chemicals applied to the skin to
destroy bacteria and prevent infection.
Irrigation—The medical name for wound flushing.

Wounds
Definition
A wound occurs when the integrity of any tissue is
compromised (e.g. skin breaks, muscle tears, burns, or
bone fractures). A wound may be caused by an act,
such as a gunshot, fall, or surgical procedure; by an
infectious disease; or by an underlying condition.

Preparation

Description

The nurse or doctor may inject the site with a local
anesthetic before flushing the wound.

Aftercare
After the wound is flushed, the health care provider cleans the area around the wound to guard
against infection. Packing to absorb excess fluids
may be placed into the wound, followed by a sterile
bandage.

Risks
Complications rarely occur, especially if the solution used to flush the wound is chosen carefully so as
to avoid skin irritation; occasionally, however, serious
infections are reported. In addition, damage to skin or
internal organs has been reported from the use of
hydrogen peroxide to flush wounds or irrigate the
abdominal cavity after surgery.
Patients should call the doctor immediately if
there is any sign of infection, such as fever, pus, or
swelling.

Types and causes of wounds are wide ranging, and
health care professionals have several different ways
of classifying them. They may be chronic, such as the
skin ulcers caused by diabetes mellitus, or acute, such
as a gunshot wound or animal bite. Wounds may also
be referred to as open, in which the skin has been
compromised and underlying tissues are exposed, or
closed, in which the skin has not been compromised,
but trauma to underlying structures has occurred (e.g.
a bruised rib or cerebral contusion). Emergency personnel and first-aid workers generally place acute
wounds in one of eight categories:


Abrasions. Also called scrapes, they occur when the
skin is rubbed away by friction against another
rough surface (e.g. rope burns and skinned knees).



Avulsions. Occur when an entire structure or part of
it is forcibly pulled away, such as the loss of a permanent tooth or an ear lobe. Explosions, gunshots,
and animal bites may cause avulsions.



Contusions. Also called bruises, these are the result
of a forceful trauma that injures an internal structure
without breaking the skin. Blows to the chest, abdomen, or head with a blunt instrument (e.g. a football
or a fist) can cause contusions.



Crush wounds. Occur when a heavy object falls onto
a person, splitting the skin and shattering or tearing
underlying structures.



Cuts. Slicing wounds made with a sharp instrument,
leaving even edges. They may be as minimal as a
paper cut or as significant as a surgical incision.



Lacerations. Also called tears, these are separating
wounds that produce ragged edges. They are produced by a tremendous force against the body, either
from an internal source as in childbirth, or from an
external source like a punch.



Missile wounds. Also called velocity wounds, they
are caused by an object entering the body at a high
speed, typically a bullet.

Normal results
The wound will heal correctly, from the inside out,
without infection.
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Dentistry in Medicine.’’ Section 9, Chapter 103 In The
Merck Manual of Diagnosis and Therapy. Whitehouse
Station, NJ: Merck Research Laboratories, 2002.
PERIODICALS

Watt, B. E., A. T. Proudfoot, and J. A. Vale. ‘‘Hydrogen
Peroxide Poisoning.’’ Toxicological Reviews 23
(January 2004): 51–57.

Carol A. Turkington
Rebecca J. Frey, PhD
4012

GALE ENCYCLOPEDIA OF MEDICINE

Punctures. Deep, narrow wounds produced by sharp
objects such as nails, knives, and broken glass.

Wounds



Causes and symptoms
Acute wounds have a wide range of causes. Often,
they are the unintentional results of motor vehicle
accidents, falls, mishandling of sharp objects, or
sports-related injury. Wounds may also be an intentional result of violence involving assault with weapons, including fists, knives, or guns.
The general symptoms of a wound are localized
pain and bleeding. Specific symptoms include:


An abrasion usually appears as lines of scraped skin
with tiny spots of bleeding.



An avulsion has heavy, rapid bleeding and a noticeable absence of tissue.



A contusion may appear as a bruise beneath the skin
or may appear only on imaging tests; an internal
wound may also generate symptoms such as weakness, perspiration, and pain.



A crush wound may have irregular margins like a
laceration; however, the wound will be deeper and
trauma to muscle and bone may be apparent.



A cut may have little or profuse bleeding depending
on its depth and length; its even edges readily line up.



A laceration too may have little or profuse bleeding;
the tissue damage is generally greater and the
wound’s ragged edges do not readily line up.



A missile entry wound may be accompanied by an
exit wound, and bleeding may be profuse, depending
on the nature of the injury.



A puncture wound will be greater than its length,
therefore there is usually little bleeding around the
outside of the wound and more bleeding inside, causing discoloration.

Diagnosis
A diagnosis is made by visual examination and
may be confirmed by a report of the causal events.
Medical personnel will also assess the extent of the
wound and the effect it has had on the patient’s well
being (e.g. profound blood loss, damage to the nervous system or skeletal system).

Treatment
Treatment of wounds involves stopping any
bleeding, then cleaning and dressing the wound to
prevent infection. Additional medical attention may
GALE ENCYCLOPEDIA OF MEDICINE

A close-up of a hard-contact gunshot wound with
accompanying burn marks on the left and right sides of the
wound. (Custom Medical Stock Photo. Reproduced by
permission.)

be required if the effects of the wound have compromised the body’s ability to function effectively.
Stopping the bleeding
Most bleeding may be stopped by direct pressure.
Direct pressure is applied by placing a clean cloth or
dressing over the wound and pressing the palm of the
hand over the entire area. This limits local bleeding
without disrupting a significant portion of the circulation. The cloth absorbs blood and allows clot formation; the clot should not be disturbed, so if blood soaks
through the cloth, another cloth should be placed
directly on top rather than replacing the original cloth.
If the wound is on an arm or leg that does not
appear to have a broken bone, the wound should be
elevated to a height above the person’s heart while
direct pressure is applied. Elevating the wound allows
gravity to slow down the flow of blood to that area.
If severe bleeding cannot be stopped by direct
pressure or with elevation, the next step is to apply
pressure to the major artery supplying blood to the
area of the wound. In the arm, pressure would be
applied to the brachial artery by pressing the inside
of the upper arm against the bone. In the leg, pressure
would be applied to the femoral artery by pressing on
the inner crease of the groin against the pelvic bone.
If the bleeding from an arm or leg is so extreme as
to be life-threatening and if it cannot be stopped by
any other means, a tourniquet may be required.
However, in the process of limiting further blood
loss, the tourniquet also drastically deprives the limb
tissues of oxygen. As a result, the patient may live but
the limb may die.
4013

Wounds
A defensive hand wound from a knife attack. (Photograph by
D. Willoughby, Custom Medical Stock Photo. Reproduced by
permission.)

In 2004, a new solution to stopping bleeding was
reported. Called QuikClot, the FDA-approved substance is made up of synthetically made material called
zeolite, which occurs naturally in volcanic rock. When
used properly, it can be poured into a wound that will
not stop bleeding and will slow blood loss. The trauma
pack costs about $50 and has shown particular promise in the battlefield and in wilderness situations.
Dressing the wound
Once the bleeding has been stopped, cleaning and
dressing the wound is important for preventing infection.
Although the flowing blood flushes debris from the
wound, running water should also be used to rinse
away dirt. Embedded particles such as wood slivers and
glass splinters, if not too deep, may be removed with a
needle or pair of tweezers that has been sterilized in
rubbing alcohol or in the heat of a flame. Once the
wound has been cleared of foreign material and washed,
it should be gently blotted dry, with care not to disturb
the blood clot. An antibiotic ointment may be applied.
The wound should then be covered with a clean dressing
and bandaged to hold the dressing in place.
Getting medical assistance
A person who has become impaled on a fixed object,
such as a fence post or a stake in the ground, should only
be moved by emergency medical personnel. Foreign
objects embedded in the eye should only be removed by
a doctor. Larger penetrating objects, such as a fishhook
or an arrow, should only be removed by a doctor to
prevent further damage as they exit.
Additional medical attention is necessary in
several instances. Wounds which penetrate the
4014

muscle beneath the skin should be cleaned and
treated by a doctor. Such a wound may require
stitches to keep it closed during healing. Some
deep wounds which do not extend to the underlying
muscle may only require butterfly bandages to keep
them closed during healing. Wounds to the face
and neck, even small ones, should always be examined and treated by a doctor to preserve sensory
function and minimize scarring. Deep wounds to
the hands and wrists should be examined for nerve
and tendon damage. Puncture wounds may require
a tetanus shot to prevent serious infection. Animal
bites should always be examined and the possibility
of rabies infection determined.
Infection
Wounds that develop signs of infection should
also be brought to a doctor’s attention. Signs of
infection are swelling, redness, tenderness, throbbing
pain, localized warmth, fever, swollen lymph glands,
the presence of pus either in the wound or draining
from it, and red streaks spreading away from the
wound.
Emergency treatment
With even as little as one quart of blood lost, a
person may lose consciousness and go into traumatic
shock. Because this is life-threatening, emergency
medical assistance should be called immediately. If
the person stops breathing, artificial respiration (also
called mouth-to-mouth resuscitation or rescue breathing) should be administered. In the absence of a pulse,
cardiopulmonary resuscitation (CPR) must be performed. Once the person is breathing unassisted, the
bleeding may be attended to.
In cases of severe blood loss, medical treatment
may include the intravenous replacement of body
fluids. This may be infusion with saline or plasma, or
a transfusion of whole blood.
In some cases, clinicians have resorted to a Civil
War-era treatment that does not sound appealing,
but works well enough to receive FDA approval.
Maggots can be placed on wounds that refuse to
heal with high-tech medical methods. The maggots
are dropped into the wound and covered with special
mesh to keep them in place. They are removed in two
to three days.

Alternative treatment
In addition to the conventional treatments
described above, there are alternative therapies that
GALE ENCYCLOPEDIA OF MEDICINE

Wounds

Abrasion

Incision

Laceration

Puncture

Avulsion

Amputation

Examples of open wounds. (Illustration by Electronic Illustrators Group.)

KEY TERMS
Abrasion—Also called a scrape. The rubbing away
of the skin surface by friction against another rough
surface.
Avulsion—The forcible separation of a piece from
the entire structure.
Butterfly bandage—A narrow strip of adhesive
with wider flaring ends (shaped like butterfly
wings) used to hold the edges of a wound together
while it heals.
Cut—Separation of skin or other tissue made by a
sharp edge, producing regular edges.
Laceration—Also called a tear. Separation of skin
or other tissue by a tremendous force, producing
irregular edges.
Plasma—The straw-colored fluid component of
blood, without the other blood cells.
Puncture—An injury caused by a sharp, narrow
object deeply penetrating the skin.
Tourniquet—A device used to control bleeding,
consisting of a constricting band applied tightly
around a limb above the wound. It should only be
used if the bleeding in life-threatening and can not
be controlled by other means.
Traumatic shock—A condition of depressed
body functions as a reaction to injury with loss
of body fluids or lack of oxygen. Signs of traumatic shock include weak and rapid pulse, shallow and rapid breathing, and pale, cool,
clammy skin.
Whole blood—Blood that contains red blood cells,
white blood cells, and platelets in plasma.

GALE ENCYCLOPEDIA OF MEDICINE

may help support the injured person. Homeopathy
can be very effective in acute wound situations.
Ledum (Ledum palustre) is recommended for puncture wounds (taken internally). Calendula (Calendula
officinalis) is the primary homeopathic remedy for
wounds. An antiseptic, it is used topically as a succus
(juice), tea, or salve. Another naturally occurring
antiseptic is tea tree oil (Melaleuca spp.), which can
be mixed with water for cleaning wounds. Aloe (Aloe
barbadensis) can be applied topically to soothe skin
during healing. When wounds affect the nerves, especially in the arms and legs, St.-John’s-wort
(Hypericum perforatum) can be helpful when taken
internally or applied topically. Acupuncture can help
support the healing process by restoring the energy
flow in the meridians that have been affected by the
wound. In some cases, vitamin E taken orally or
applied topically can speed healing and prevent
scarring.

Prognosis
Without the complication of infection, most
wounds heal well with time. Depending on the depth
and size of the wound, it may or may not leave a visible
scar.

Prevention
Most actions that result in wounds are preventable. Injuries from motor vehicle accidents may be
reduced by wearing seat belts and placing children
in size-appropriate car seats in the back seat.
Sharp, jagged, or pointed objects or machinery
parts should be used according to the manufacturer’s instructions and only for their intended
purpose. Firearms and explosives should be used
only by adults with explicit training; they should
4015

Wounds

also be kept locked and away from children.
Persons engaging in sports, games, and recreational
activities should wear all proper protective equipment and follow safety rules.

ORGANIZATIONS

Resources

American Red Cross. P.O. Box 37243, Washington, D.C.
20013. <http://www.redcross.org>.

Thornton, Jim. ‘‘Stop the Bleeding! An Innovative
Treatment for Wilderness Wounds’’ Field & Stream
September 1, 2004: 48.

PERIODICALS

‘‘Maggots Make Medical Comeback for Healing
Wounds.’’ Health & Medicine Week August 23,
2004: 287.

4016

Bethany Thivierge
Teresa G. Odle

Wryneck see Torticollis

GALE ENCYCLOPEDIA OF MEDICINE

X

X-linked agammaglobulinemia
Definition
X-linked agammaglobulinemia (XLA) or
Bruton’s agammaglobulinemia is present at birth
(congenital) and is characterized by low or completely
absent levels of immunoglobulins in the bloodstream.
Immunoglobulins are protein molecules in blood
serum that function like antibodies. Without them,
the body lacks a fully functioning immune system.
Persons with XLA are vulnerable to repeated, potentially fatal bacterial infections.

Description
XLA occurs in one in 50,000 to one in 100,000
newborns. Almost all persons with the disorder are
males. Although persons with XLA carry the genes
to produce immunoglobulins, a genetic defect on the X
chromosome prevents their formation. This defect is
not associated with the immunoglobulins themselves,
but rather with the B cells in the bloodstream that
ordinarily secrete the immunoglobulins.
B cells are a type of white blood cell. They are the
sole producers of immunoglobulins in the body. B cells
are produced in the bone marrow and carried to the
spleen, lymph nodes, and other organs as they mature.
The maturation process depends on an enzyme called
Bruton’s agammaglobulinemia tyrosine kinase (Btk).
If Btk is missing or defective, the B cells cannot mature
and cannot produce immunoglobulins.
The gene for Btk is on the X chromosome. Certain
changes (mutations) in this gene result in defective
Btk. Since the gene is carried on the X chromosome,
XLA individuals are almost always male. Females
have two X chromosomes, which means they have
two copies of the Btk gene, one of which is normal.
Males have only one X chromosome.
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
XLA is caused by a defect in the gene that codes for
Btk. This defect leads to blocked maturation of B cells,
the cells that produce immunoglobulins. Because other
portions of the immune system are functional, people
with XLA can fight off some types of infection, such as
fungal and most viral infections. Immunoglobulins,
however, are vital to combat bacterial infections.
Infants with XLA usually do not show symptoms during the first six months of life because immunoglobulins
from their mothers are circulating in their bloodstreams. As the mother’s supply decreases, the baby
becomes increasingly vulnerable to bacterial infections.
Common symptoms of immunoglobulin deficiency appear after the infant is six months old. They
include frequent ear and sinus infections, pneumonia,
and gastroenteritis. Certain viruses, such as hepatitis
and polio viruses, can also pose a threat. Children with
XLA grow slowly, have small tonsils and lymph
nodes, and may develop chronic skin infections.
Approximately 20% of these children develop arthritis, possibly as a result of joint infections.

Diagnosis
Frequent bacterial infections, a lack of mature B
cells, and low-to-nonexistent levels of immunoglobulins point to a diagnosis of XLA. A sample of the
infant’s blood serum can be analyzed for the presence
of immunoglobulins by a technique called immunoelectrophoresis. To make a definitive diagnosis, the
child’s X chromosome is analyzed for defects in the
Btk gene. Similar analysis can be used for prenatal
diagnosis or to detect carriers of the defective gene.

Treatment
Treatment of XLA consists of regular intravenous
doses of commercially prepared gamma globulin (sold
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X rays of the orbit

Resources

KEY TERMS
Antibody—A molecule that is produced by the
immune system in response to a protein, called an
antigen, that is not recognized as belonging in the
body.
B cell—A type of lymphocyte, or white blood cell,
that is a key component of the body’s immune
system. Mature B cells produce immunoglobulins.
Bruton’s agammaglobulinemia tyrosine kinase
(Btk)—An enzyme vital for the maturation of B cells.
Carrier—A person who has a genetic defect but
does not develop any symptoms or signs of the
defect. The carrier’s offspring may inherit the defect
and develop the associated disorder.
Enzyme—A protein molecule that prompts rapid
biochemical reactions.
Immunoglobulin—A protein molecule formed by
mature B cells in response to foreign proteins in the
body. There are five types of immunoglobulins, but
the major one is gamma globulin or immunoglobulin G.
Mutation—A change in a gene that alters the function or other characteristics of the gene’s product.
X chromosome—One of the two sex chromosomes
(the other is Y) that determine a person’s gender.
Normal males have both an X and a Y chromosome,
and normal females have two X chromosomes.

under the trade names Gamimune or Gammagard) to
ward off infections. Antibiotics are used to treat infections as they occur. Children with XLA must be treated
promptly for even minor cuts and scrapes, and taught to
avoid crowds and people with active infections.

Prognosis
Prior to the era of gamma globulin and antibiotic
treatment, approximately 90% of XLA individuals
died before age 8. Early diagnosis and current therapy
allows most individuals with XLA to reach adulthood
and lead relatively normal lives. Infants who develop
polio or persistent viral infections, however, have a
poorer prognosis.

Prevention
Parents of a child with XLA should consider genetic
counseling if they are planning to have more children.
4018

ORGANIZATIONS

Immune Deficiency Foundation. 25 W. Chesapeake Ave.,
Suite 206, Towson, MD 21204. (800) 296-4433.
<http://www.primaryimmune.org>.
National Organization for Rare Disorders. P.O. Box 8923,
New Fairfield, CT 06812-8923. (800) 999-6673.
<http://www.rarediseases.org>.

Julia Barrett

X rays of the eye’s orbit see X rays of the orbit

X rays of the orbit
Definition
Orbital x rays are studies of the area and structures containing the eye. The orbit is the circle of thin
bones that houses and protects the eye, even extending
behind the eye and nearly wrapping around it. The
orbit includes the eyebrow, the bridge of the nose and
the cheekbone. X rays are a form of radiation (like
light) that can penetrate body tissues.

Purpose
Orbital x ray, or orbital radiography, is often used
to detect problems resulting from injury or trauma to
the eye. The exam may also detect changes to the
structure of the eye, which may indicate various diseases. An ophthalmologist may also order an orbital
x ray if there is concern that foreign bodies may be
present in the eye that cannot be detected with an
instrument called an ophthalmoscope.

Precautions
Pregnant women and women who could possibly
be pregnant should only receive orbital x rays when
absolutely necessary. If the patient is in severe pain due
to injury or trauma, a painkiller may be given to help
ease discomfort during positioning of the head
throughout the exam. No other precautions are necessary for orbital x rays.

Description
Each orbit is composed of a floor, a roof, a medial
(in the center plane) and lateral (sides of the plane)
walls. The orbital x ray involves several different views
in order for the physician to clearly see various parts of
GALE ENCYCLOPEDIA OF MEDICINE

The orbital x ray procedure should take about
15 minutes to complete. Following the procedure,
the patient will usually be asked to wait until the
films are developed to ensure they are high enough
quality and that repeat x rays are not necessary. A
physician may perform the x ray exam in his or her
office, or refer the patient to an outpatient radiology facility or hospital radiology department. In
the case of emergency, the exam may be performed
in the emergency room or a nearby radiology area
of the hospital.

Preparation
There are no special dietary preparations
needed prior to an orbital x ray. As with any radiography procedure, the patient should remove any
jewelry or metal objects, which may interfere with
a clear image.

Aftercare
No aftercare is required following this diagnostic
test.

Risks
Radiation exposure is low for this procedure and
all certified radiology facilities follow strict personnel
and equipment guidelines for radiation protection.
Women of child bearing age and children should be
offered protective shielding (lead aprons) to cover the
genital and/or abdominal areas.

Normal results
Normal findings will show the bones of the orbit
intact, and will show similarity between the orbit that
is being studied and the unaffected orbit.

Abnormal results
Positive findings from an orbital x ray may show
that there has been injury to the eye. Certains signs
GALE ENCYCLOPEDIA OF MEDICINE

KEY TERMS
Blowout fracture—A fracture or break in the orbit
that is caused by sudden and violent impact to the
area.
Malignancy—A malignancy is a tumor that is cancerous and growing.
Medial wall—The middle bone, or wall of the eye’s
orbit. It is generally thicker than the roof and floor
walls.
Ophthalmologist—A physician who specializes in
the workings, structures and care of the eyes.
Ophthalmoscope—An instrument routinely used
by ophthalmologists to examine the interior of the
eye. It consists of a small light, a mirror, and lenses
of differing powers that magnify.
Radiography—Examination of any part of the
body through the use of x rays. The process
produces an image of shadows and contrasts
on film.
X ray—A form of electromagnetic radiation with
shorter wavelengths than normal light. X rays can
penetrate most structures.

may indicate some disease that is affecting the orbital
structures. Tiny fractures in the orbital bones can
usually be detected on the radiograph. The floor
bone, the medial wall and the ethmoid bone, which is
a spongy bone that forms the upper part of the nasal
cavity, are the most likely to break. In a blowout
fracture (one involving the orbital floor), radiographic
findings may include disruption to the orbital floor, an
opaque look to the sinuses on the same side as the
affected orbit (due to hemorrhage) or signs of sinus
problems from the orbital root’s interference. These
indications can be seen in most typical orbital x ray
views.
Since the physician examines both orbits side
by side, indications of differences in size and shape
of the various structures in the orbit may be apparent. The orbit may be enlarged, indicating irritation
from an injury or foreign body. A number of growing tumors within the eye or brain area may also
cause orbital enlargement. Destruction of the walls
of the orbit may indicate a nearby infection or
malignancy. Changes in density of the tiny orbit
bones may also be a sign of bone disease or cancer
spread to bone.
4019

X rays of the orbit

the eye without obstruction. In orbital x rays, images
of the unaffected eye may also be taken to compare its
shapes and structures to those of the affected eye.
Views may include side view (lateral), back to front
(posteroanterior), base view, views from both sides,
and an image from the center to one outside edge (halfaxial projection). Projections of the optical canal will
also be included. For all of these views, the patient
may be seated upright or asked to lie on a table in the
x ray room.

X rays of the orbit

Children’s orbits are more likely to be enlarged by
a fast growing lesion, since their orbital bones have not
fully developed.

National Eye Institute. 2020 Vision Place, Bethesda, MD
20892-3655. (301) 496-5248. <http://
www.nei.nih.gov>.
OTHER

Resources
ORGANIZATIONS

American Academy of Ophthalmology. 655 Beach Street,
P.O. Box 7424, San Francisco, CA 94120-7424.
<http://www.eyenet.org>.

4020

Scgeue Eye Institute. University of PennsylvaniaHealth
System. <http://www.med.upenn.edu/ophth>.

Teresa Odle

Xerophthalmia see Vitamin A deficiency

GALE ENCYCLOPEDIA OF MEDICINE

Y
Yaws
Definition
Yaws is a chronic illness which first affects the
skin, and then affects the bones.

Description
Yaws tends to strike children, particularly
between the ages of two and five. It is common in
areas where poverty and overcrowding interfere with
good hygiene practices. The most common locations
are in rural areas throughout Africa, Southeast Asia,
and in locations bordering the equator in the
Americas.

Causes and symptoms
Yaws is caused by a spiral-shaped bacterium (spirochete) called Treponema pertenue. This bacterium
belongs to the same family as the bacterium that
causes syphilis.
Yaws is passed among people by direct skin contact. It requires some kind of a scratched or insect
bitten area in order for the bacteria to actually settle
in and cause infection. An injured spot on the leg is the
most common part of the body through which the
bacteria enter. Young children, who are constantly
bumping themselves in play, who wear little clothing,
who do not wash their hands often, and who may
frequently put their hands in their mouths, are particularly susceptible.
The first symptom of yaws occurs three to four
weeks after acquiring the bacteria. The area where the
bacteria originally entered the skin becomes a noticeable bump (papule). The papule grows larger and
develops a punched-out center (ulcer), covered with a
yellow crust. Lymph nodes in the area may become
swollen and tender. This first papule may take as long
GALE ENCYCLOPEDIA OF MEDICINE

as six months to heal. Secondary soft, gummy growths
then appear on the face, arms and legs, and buttocks.
These soft, tumor-like masses may grow on the soles of
the feet, causing the patient to walk in an odd and
characteristic fashion on the sides of his or her feet
(nicknamed ‘‘crab yaws’’). More destructive tumors
may then disrupt the bones of the face, the jaw, and
the lower leg. Ulcers around the nose and on the face
may be very mutilating.

Diagnosis
Samples taken from the first papules may be
examined using a technique called dark-field microscopy. This often allows the spirochetes to be identified. They may also be identified in fluid withdrawn
from swollen lymph nodes. Various tests can also be
run on blood samples to determine if an individual is
producing antibodies (special immune cells) which are
specifically made in response to the presence of these
spirochetes.

Treatment
A single penicillin injection in a muscle is sufficient to completely end the disease.

Prognosis
Without treatment, yaws is a terribly disfiguring
chronic illness. With appropriate treatment, the progression of the disease can be completely halted.

Prevention
For a time, the World Health Organization
(WHO) was working to totally eradicate yaws, just
as smallpox was successfully eradicated. This has not
occurred, however. WHO continues to work to identify and respond to outbreaks quickly, in an effort to
at least slow the spread of yaws.
4021

Yellow fever

KEY TERMS

WILBUR AUGUSTUS SAWYER
(1879–1951)

Papule—A raised bump on the skin.
Ulcer—A punched-out, irritated pit on the skin.

Resources
ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton
Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404)
639-3311. <http://www.cdc.gov>.

Rosalyn Carson-DeWitt, MD

Yellow fever
Definition
Yellow fever, which is also known as sylvatic fever
and viral hemorrhagic fever or VHF, is a severe infectious disease caused by a type of virus called a flavivirus. This flavivirus can cause outbreaks of epidemic
proportions throughout Africa and tropical America.
The first written evidence of such an epidemic
occurred in the Yucatan in 1648. Since that time,
much has been learned about the interesting transmission patterns of this devastating illness. It is thought
that the disease originated in Africa and spread to the
Americas in the 17th and 18th centuries through trading ships. The flavivirus that causes yellow fever was
first identified in 1928 and the first vaccine against the
disease was produced at the Rockefeller Institute in
New York in 1937.

Description
In order to understand how yellow fever is passed,
several terms need to be defined. The word ‘‘host’’
refers to an animal that can be infected with a particular disease. The term ‘‘vector’’ refers to an organism
which can carry a particular disease-causing agent
(such as a virus or bacteria) without actually developing the disease. The vector can then pass the virus or
bacterium on to a new host.
Many of the common illnesses in the United
States (including the common cold, many viral causes
of diarrhea, and influenza or ‘‘flu’’) are spread via
direct passage of the causative virus between human
4022

Wilbur Augustus Sawyer was born in Appleton,
Wisconsin, on August 7, 1879, to Minnie Edmea (Birge)
and Wesley Caleb Sawyer. The Sawyers moved to
Oshkosh, Wisconsin and finally to Stockton, California
in 1888. Sawyer spent two years at the University of
California and then entered Harvard College where he
earned his A.B. degree in 1902. In 1906, Sawyer graduated from Harvard Medical School and began a private
practice, which lasted until he started his internship at
Massachusetts General Hospital. Sawyer returned to
California in 1908 in order to obtain a position at the
University of California as a medical examiner. He then
worked with California State Board of Health from 1910
until 1918. In 1911, Sawyer married Margaret
Henderson. The couple had three children.
Sawyer’s first publication (1913) dealt with his
research of poliomyelitis. His discovery, in 1915, that
examination of the individual’s stool could lead to detection of the disease was later regarded as very significant.
In 1918 and 1919, Sawyer worked to control venereal
disease while employed by the Army Medical Corps. In
1926 and 1927, while director of the West African
Yellow Fever Commission, Sawyer succeeded in isolating the yellow fever virus. He would ultimately return to
the United States, where he and Wray Lloyd would
devise an immunization against yellow fever (1931).
In 1944, Sawyer became director of health for the
United Nations Relief and Rehabilitation Administration,
a position he held for three years. He retired to Berkeley,
California where he died on November 12, 1951.

beings. Yellow fever, however, cannot be passed
directly from one infected human being to another.
Instead, the virus responsible for yellow fever requires
an intermediate vector, a mosquito, which carries the
virus from one host to another.
The hosts of yellow fever include both humans
and monkeys. The cycle of yellow fever transmission
occurs as follows: an infected monkey is bitten by a
tree-hole breeding mosquito. This mosquito acquires
the virus, and can pass the virus on to any number of
other monkeys that it may bite. This form of yellow
fever is known as sylvatic yellow fever, and usually
affects humans only incidentally. When a human is
bitten by an infected mosquito, however, the human
may acquire the virus. In the case of South American
yellow fever, the infected human may return to the
city, where an urban mosquito (Aedes aegypti) serves
GALE ENCYCLOPEDIA OF MEDICINE

Yellow fever epidemics may also occur after
flooding caused by earthquakes and other natural
disasters. They result from a combination of new
habitats available for the vectors of the disease and
changes in human behavior (spending more time outdoors and neglecting sanitation precautions).
Cases of yellow fever are uncommon in the United
States and Canada as of 2004. The last reported case in
an American citizen concerned a man who contracted
yellow fever in Brazil in 1996. The last epidemic in the
United States occurred in New Orleans in 1905.

Symptoms
Once a mosquito has passed the yellow fever virus
to a human, the chance of disease developing is about
5–20%. Infection may be fought off by the host’s
immune system, or may be so mild that it is never
identified.
In human hosts who develop the disease yellow
fever, there are five distinct stages through which the
infection evolves. These have been termed the periods
of incubation, invasion, remission, intoxication, and
convalescence.
Yellow fever’s incubation period (the amount of
time between the introduction of the virus into the
host and the development of symptoms) is three to
six days. During this time, there are generally no
symptoms identifiable to the host.
The period of invasion lasts two to five days, and
begins with an abrupt onset of symptoms, including
fever and chills, intense headache and lower backache,
muscle aches, nausea, and extreme exhaustion. The
patient’s tongue shows a characteristic white, furry
coating in the center, surrounded by a swollen, reddened margin. While most other infections that cause
a high fever also cause an increased heart rate, yellow
fever results in an unusual finding, called Faget’s sign.
This is the simultaneous occurrence of a high fever
with a slowed heart rate. Throughout the period of
invasion, there are still live viruses circulating in the
patient’s blood stream. Therefore, a mosquito can bite
the ill patient, acquire the virus, and continue passing
it on to others.
The next phase is called the period of remission.
The fever falls, and symptoms decrease in severity for
several hours to several days. In some patients, this
signals the end of the disease; in other patients, this
proves only to be the calm before the storm.
GALE ENCYCLOPEDIA OF MEDICINE

The period of intoxication represents the most
severe and potentially fatal phase of the illness. During
this time, lasting three to nine days, a type of degeneration of the internal organs (specifically the kidneys, liver,
and heart) occurs. This fatty degeneration results in
what is considered the classic triad of yellow fever symptoms: jaundice, black vomit, and the dumping of protein
into the urine. Jaundice causes the whites of the patient’s
eyes and the patient’s skin to take on a distinctive yellow
color. This is due to liver damage, and the accumulation
of a substance called bilirubin, which is normally processed by a healthy liver. The liver damage also results in
a tendency toward bleeding; the patient’s vomit appears
black due to the presence of blood. Protein, which is
normally kept out of the urine by healthy, intact kidneys, appears in the urine due to disruption of the kidney’s healthy functioning.
Patients who survive the period of intoxication
enter into a relatively short period of convalescence.
They recover with no long term effects related to the
yellow fever infection. Further, infection with the yellow fever virus results in lifelong immunity against
repeated infection with the virus.
The course of yellow fever is complicated in some
patients by secondary bacterial infections.

Diagnosis
Diagnosis of yellow fever depends on the examination of blood by various techniques in order to demonstrate either yellow fever viral antigens (the part of the
virus that stimulates the patient’s immune system to
respond) or specific antibodies (specific cells produced
by the patient’s immune system which are directed
against the yellow fever virus). The most rapid method
of diagnosis as of 2004 is capture enzyme immunoassay.
The diagnosis can be strongly suspected when Faget’s
sign is present. When the classic triad of symptoms is
noted yellow fever is strongly suspected.

Treatment
There are no antiviral treatments available as of
2004 to combat the yellow fever virus, although
researchers at the University of Texas are studying ribavirin (Virazole, Rebetol), a drug that is given by mouth
to treat hepatitis C, as a potential treatment for liver
damage caused by yellow fever. The only treatments for
yellow fever are given to relieve its symptoms. Fevers
and pain should be relieved with acetaminophen, not
aspirin or ibuprofen, both of which could increase the
already-present risk of bleeding. Dehydration (due to
fluid loss both from fever and bleeding) needs to be
4023

Yellow fever

as a viral vector, spreading the infection rapidly by
biting humans. This form of the disease is known as
urban yellow fever or epidemic yellow fever.

Yellow fever

KEY TERMS
Epidemic—A situation in which a particular disease spreads rapidly through a population of people
in a relatively short period of time.
Faget’s sign—The simultaneous occurrence of a
high fever with a slowed heart rate.
Host—The organism (such as a monkey or human)
in which another organism (such as a virus or bacteria) is living.
Sylvatic—Pertaining to or living in the woods or
forested areas. The form of yellow fever transmitted
by mosquitoes to rainforest monkeys is called sylvatic yellow fever.
Vector—A carrier organism (such as a fly or mosquito) which serves to deliver a virus (or other agent
of infection) to a host.

carefully avoided. This can be accomplished by increasing fluids. The risk of bleeding into the stomach can
be decreased through the administration of antacids and
other medications. Hemorrhage may require blood
transfusions. Kidney failure may require dialysis
(a process that allows the work of the kidneys in clearing
the blood of potentially toxic substances to be taken
over by a machine, outside of the body).

Prognosis
Five to ten percent of all diagnosed cases of yellow
fever are fatal. Jaundice occurring during a yellow fever
infection is an extremely grave predictor. Twenty to
fifty percent of these patients die of the infection.
Death may occur due to massive bleeding (hemorrhage), often following a lapse into a comatose state.

Prevention
A very safe and very effective yellow fever vaccine
exists. The Arilvax vaccine is made from a live attenuated form of the yellow fever virus, strain 17D. In the
United States, the vaccine is given only at Yellow
Fever Vaccination Centers authorized by the U.S.
Public Health Service. About 95% of vaccine recipients acquire long-term immunity to the yellow fever
virus. Careful measures to decrease mosquito populations in both urban areas and jungle areas in which
humans are working, along with programs to vaccinate all people living in such areas, are necessary to
avoid massive yellow fever outbreaks.
4024

Persons planning to travel to countries where yellow fever in endemic may obtain up-to-date information on yellow fever vaccination from the Centers for
Disease Control and Prevention by telephone (404332-4559) or fax (404-332-4265).
Resources
BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors.
‘‘Viral Diseases.’’ Section 13, Chapter 162 In The Merck
Manual of Diagnosis and Therapy. Whitehouse Station,
NJ: Merck Research Laboratories, 2002.
PERIODICALS

Barrett, A. D. ‘‘Current Status of the Arilvax Yellow Fever
Vaccine.’’ Expert Review of Vaccines 3 (August 2004):
413–420.
Lo Re, V., III, and S. J. Gluckman. ‘‘Travel
Immunizations.’’ American Family Physician 70 (July 1,
2004): 89–99.
Reeder, G. David, MD, and Theodore E. Woodward, MD.
‘‘Yellow Fever.’’ eMedicine February 25, 2002.
<http://www.emedicine.com/med/topic2432.htm>.
Sbrana, E., S. Y. Xiao, H. Guzman, et al. ‘‘Efficacy of
Post-Exposure Treatment of Yellow Fever with
Ribavirin in a Hamster Model of the Disease.’’
American Journal of Tropical Medicine and Hygiene 71
(September 2004): 306–312.
ORGANIZATIONS

Centers for Disease Control and Prevention (CDC). 1600
Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435,
(404) 639-3311. <http://www.cdc.gov>.
Infectious Diseases Society of America (IDSA). 66 Canal
Center Plaza, Suite 600, Alexandria, VA 22314. (703)
299-0200. Fax: (703) 299-0204. <http://
www.idsociety.org>.
World Health Organization (WHO). <http://www.who.int/
en/>.
OTHER

World Health Organization Fact Sheet. ‘‘Flooding and
Communicable Diseases Fact Sheet: Risk Assessment
and Preventive Measures.’’ December 2004. <http://
www.who.int/hac/techguidance/ems/flood_cds/en/
index.html>.

Rosalyn Carson-DeWitt, MD
Rebecca J. Frey, PhD

Yersinia enterocolitica infection see
Yersinosis
Yersinia pestis see Plague
Yersinia pseudotuberculosis infection see
Yersinosis
GALE ENCYCLOPEDIA OF MEDICINE

Definition
Yersinosis refers to infection by a genus of bacteria known as Yersinia. The two sub-types that are
responsible for yersinosis are Yersinia enterocolitica
and Yersinia pseudotuberculosis. The diseases produced by these organisms are called ‘‘zoonoses,’’
because the bacteria is passed to humans from animal
sources.
The name Yersinia comes from Dr. Alexandre
Yersin, who was the first person to grow a much
more deadly type of Yersinia known as Yersinia pestis,
the bacteria responsible for what is now known as
bubonic plague. This article, however, will deal with
the more common forms of Yersinia, namely Y. enterocolitica and Y. pseudotuberculosis.

Description
Yersinia are classified as gram-negative bacteria
(bacteria that do not accept the color of a stain in a
Gram stain test, which indicates the general chemical
nature of the cell wall of the bacteria); they have a
variety of appearances, and are therefore called pleomorphic. They belong to Enterobacteriacae, the large
group of organisms that inhabit the intestinal tract.
There are many different subtypes of Yersinia.
They are found worldwide and have been isolated
from soil, fresh water, contaminated foods, and many
wild and domestic animals. For reasons not entirely
clear, disease caused by these organisms occurs more
frequently in areas of northern Europe, especially
Scandinavia. Infection, particularly in children ages
one through four years, is quite common, though
often these infections produce few symptoms. Studies
have shown that infection with these bacteria is almost
as common as that with Shigella or Campylobacter.

Causes and symptoms
Animals are the most important sources of bacterial infection for humans. Whether from pets or
undercooked meat (especially pork), these bacteria
almost always enter the human body through the
mouth (oral transmission). An incubation period of
one to eleven days passes before signs of disease
develop. Rare cases have been transmitted by way of
contaminated blood transfusions.
Yersinia produces several different types of disease. The most common form is a short-lived inflammation of the intestine known as enterocolitis. Most
GALE ENCYCLOPEDIA OF MEDICINE

In other patients, the same area of the intestine
is involved, but instead of causing diarrhea, a syndrome resembling appendicitis occurs. In this
syndrome, the lymph nodes surrounding the intestine
are especially involved; this has lead to the term
mesenteric adenitis. Although this syndrome resolves
without serious consequences, it is often difficult to
differentiate from appendicitis, and leads to surgery
in some instances. Ultrasound exam may be able to
demonstrate a normal appendix and avoid surgery.
Why some patients develop symptoms of gastroenteritis, and others only inflammation, pain, and
fever, is unknown.
In some patients, Yersinia produces infection of
areas other than the intestinal tract. These include:


Inflammation of the throat (pharyngitis) and tonsillitis; this can be quite severe and even lead to death,
particularly in adults.



Septicemia, or infection of the blood stream, with
spreading of infection to other organs such as bone,
meninges, kidneys, and others. Individuals with
decreased immunity due to liver disease, diabetes,
cancer, and other diseases are at increased risk for
this complication.

Different parts of the body may be affected (such
as joints, eyes, and urinary system) by changes in the
immune system caused by
Yersinia infection.
Arthritis, which is especially frequent in Scandinavia,
occurs in up to 10% of Yersinia infections. About one
week after typical intestinal symptoms, swelling and
pain in multiple joints occurs. The knees and ankles
are most often involved, and become inflamed over a
period of two weeks. In two-thirds of those affected,
symptoms gradually resolve over one to three months
without need for treatment. Rarely does chronic joint
disease develop.
Inflammation of the heart muscle, called myocarditis, sometimes occurs together with the arthritis. In
about 15-20% of patients, the skin develops a red,
raised area, usually located on the shins, called
erythema nodosum. This appears within a few weeks
of the intestinal symptoms and disappears over a
month or so.
4025

Yersinosis

Yersinosis

often the very end of the small intestine is involved,
an area known as the terminal ileum. The result is
gastroenteritis, with cramping abdominal pain, fever,
and diarrhea. Diarrhea generally continues for two
weeks or so, but can go on for many months. Up to
40% of patients also experience nausea and vomiting;
and in one-third, inflammation of the intestine leads to
bleeding.

Yoga

KEY TERMS
Mesenteric adenitis—Inflammation of the lymph
nodes which serve the small intestine. Has symptoms similar to appendicitis.
Septicemia—Systemic disease associated with the
presence of microorganisms or their toxins in the
blood; blood poisoning.

infections occur in those with decreased immunity.
Death rate from septicemia has been reported to be
as high as 50%.

Prevention
Safe food handling procedures and food-preparation practices are by far the best means of avoiding
infection. Undercooked food, especially pork or other
animal products, should not be eaten.
Resources

Diagnosis
Identifying Yersinia as the cause of all or any of
these symptoms is not an easy task. It is possible to
grow the organism from stool cultures, but this is
difficult to do unless special methods are used.
A change in antibody levels can also be used to
determine the presence of infection. To be accurate,
levels must be initially examined early in the illness.
Therefore, it is most important for the possible diagnosis and examination to be thought of early.

Treatment
Since most of the symptoms caused by Yersinia
are self limiting, specific antibiotic treatment is generally not needed. Patients with dehydration from gastroenteritis are given supportive therapy, including
treatment aimed at replacing fluids.
Antibiotics are indicated, however, for those
patients who develop more severe infections, such as
invasion of the bloodstream (septicemia), or who
develop infections at specific sites, such as bone. A
variety of antibiotics have been used, but it is not
clear which produces the best results.
No specific treatment is indicated for the joint, ocular, skin, or urinary symptoms that result from infection.
As stated, these are not due to direct invasion by the
bacteria, but are related to changes in immune reactions
produced by the infection. However, treatment of those
experiencing severe arthritic symptoms with NSAIDS
(nonsteroidal anti-inflammatory drugs) or steroid injection at inflamed joints is used in selected cases.

Prognosis
As noted above, most of the time, Yersinia infection has an excellent outlook. However, when these
bacteria invade the bloodstream or produce disease
beyond the gastrointestinal tract, the outlook is
less positive. This may be because more severe
4026

OTHER

‘‘Bad Bug Book.’’ Center for Food Safety and
AppliedNutrition.<http://vm.cfsan.fda.gov/~mow/
intro.html>.

David Kaminstein, MD

Yoga
Definition
The term yoga comes from a Sanskrit word which
means yoke or union. Traditionally, yoga is a method
joining the individual self with the Divine, Universal
Spirit, or Cosmic Consciousness. Physical and mental
exercises are designed to help achieve this goal, also
called self-transcendence or enlightenment. On the
physical level, yoga postures, called asanas, are
designed to tone, strengthen, and align the body.
These postures are performed to make the spine supple
and healthy and to promote blood flow to all the
organs, glands, and tissues, keeping all the bodily
systems healthy. On the mental level, yoga uses
breathing techniques (pranayama) and meditation
(dyana) to quiet, clarify, and discipline the mind.
However, experts are quick to point out that yoga is
not a religion, but a way of living with health and
peace of mind as its aims.

Purpose
Yoga has been used to alleviate problems associated with high blood pressure, high cholesterol,
migraine headaches, asthma, shallow breathing, backaches, constipation, diabetes, menopause, multiple
sclerosis, varicose veins, carpal tunnel syndrome and
many chronic illnesses. It also has been studied and
approved for its ability to promote relaxation
and reduce stress.
GALE ENCYCLOPEDIA OF MEDICINE

There is little historical information available on
Patanjali, who is credited with developing yoga, one of
the six systems of Hindu philosophy. Several scholars suggest several persons may have developed yoga under the
pseudonym of Patanjali. In any case, Patanjali existed
around 150 B.C. in India. He developed yoga based on a
loose set of doctrines and practices from the Upanishads,
themselves a set of mystical writings. The Upanishads
are part of the Aranyakas, philosophical concepts that are
part of the Veda, the most ancient body of literature of
Hinduism. Patanjali gave these combined philosophical
and esoteric writings a common foundation in his Yoga
Sutra, a set of 196 concise aphorisms (wise sayings) that
form the principles of yoga. He also drew upon Samkhya,
the oldest classic system of Hindu philosophy. Patanjali’s
yoga accepted Samkhya metaphysics and the concept of a
supreme soul. He established an eight-stage discipline of
self-control and meditation. The individual sutras (verses)
lay out the entire tradition of meditation. They also
describe the moral and physical disciplines needed for
the soul to attain absolute freedom from the body and self.

As of late 2002, yoga is increasingly recommended
for dysmenorrhea, premenstrual syndrome, and other
disorders in premenopausal women, in Europe as well
as in the United States.
Yoga can also provide the same benefits as any welldesigned exercise program, increasing general health
and stamina, reducing stress, and improving those conditions brought about by sedentary lifestyles. Yoga has
the added advantage of being a low-impact activity that
uses only gravity as resistance, which makes it an excellent physical therapy routine; certain yoga postures can
be safely used to strengthen and balance all parts of the
body. A study published in late 2002 summarized recent
findings about the benefits of yoga for the cardiovascular and musculoskeletal systems. The review noted that
yoga is still viewed as a ‘‘trendy’’ form of exercise rather
than one with documented medical benefits.
Meditation has been much studied and approved
for its benefits in reducing stress-related conditions. The
landmark book,The Relaxation Response, by Harvard
cardiologist Herbert Benson, showed that meditation
and breathing techniques for relaxation could have the
opposite effect of stress, reducing blood pressure and
other indicators. Since then, much research has reiterated the benefits of meditation for stress reduction and
GALE ENCYCLOPEDIA OF MEDICINE

general health. Currently, the American Medical
Association recommends meditation techniques as a
first step before medication for borderline hypertension
cases. Some 2002 studies indicate that yogic meditation
by itself is effective in lowering serum cholesterol as well
as blood pressure.
Modern psychological studies have shown that
even slight facial expressions can cause changes in
the involuntary nervous system; yoga utilizes the
mind/body connection. That is, yoga practice contains
the central ideas that physical posture and alignment
can influence a person’s mood and self-esteem, and
also that the mind can be used to shape and heal the
body. Yoga practitioners claim that the strengthening
of mind/body awareness can bring eventual improvements in all facets of a person’s life.

Description
Origins
Yoga originated in ancient India and is one of the
longest surviving philosophical systems in the world.
Some scholars have estimated that yoga is as old as
5,000 years; artifacts detailing yoga postures have been
found in India from over 3000 B.C. Yoga masters
( yogis) claim that it is a highly developed science of
healthy living that has been tested and perfected for all
these years. Yoga was first brought to America in the
late 1800s when Swami Vivekananda, an Indian teacher and yogi, presented a lecture on meditation in
Chicago. Yoga slowly began gaining followers, and
flourished during the 1960s when there was a surge of
interest in Eastern philosophy. There has since been a
vast exchange of yoga knowledge in America, with
many students going to India to study and many
Indian experts coming here to teach, resulting in the
establishment of a wide variety schools. Today, yoga is
thriving, and it has become easy to find teachers and
practitioners throughout America. A recent Roper
poll, commissioned byYoga Journal, found that 11
million Americans do yoga at least occasionally and 6
million perform it regularly. Yoga stretches are used by
physical therapists and professional sports teams, and
the benefits of yoga are being touted by movie stars and
Fortune 500 executives. Many prestigious schools of
medicine have studied and introduced yoga techniques
as proven therapies for illness and stress. Some medical
schools, like UCLA, even offer yoga classes as part of
their physician training program.
Classical yoga is separated into eight limbs, each
a part of the complete system for mental, physical
and spiritual well-being. Four of the limbs deal with
mental and physical exercises designed to bring the
4027

Yoga

P A T A N J A L I (CIRCA SECOND
CENTURY B.C.–CIRCA SECOND
CENTURY B.C.)

Yoga

Yoga Positions

Yoga Positions (continued)

Name

Description

Abdominal
massage

Kneel with arms folded. Bend torso toward ground
and lower forehead to the floor. Slowlly raise up,
switch arms, and repeat.
Lying on stomach, raise head, torso, arms, and legs
off the ground and stretch. Arms should be outstretched and pointing towards feet.
Lying on stomach, hold ankles from behind and
slowly raise head, torso, and thighs off floor.
Lying on back with knees bent and feet flat on floor,
raise pelvis off floor and arch back. Arms should be
stretched out on floor with hands grasped.
On hands and knees, move head and buttocks as far
left as possible. Inhale as you return center and repeat
on the right side.
While kneeling, arch back and bend head back toward
feet. Hold heels with hands and exhale while in
movement.
On hands and knees, arch back and exhale while in
movement, rounding shoulders and back.
Kneeling with arms to the side, roll torso to floor and
rest forehead on the ground.
Stretched out on floor with stomach down, place
elbows parallel to shoulders and raise torso up. Arms
should straighten with hands flat on floor.
Lie on back with feet and arms outstretched. Breathe
deeply.
On hands and knees, dip back and lift head and
buttocks up. Exhale.
On hands and knees form and inverted V by pushing
pelvis up and pressing hands and heels to floor.
Exhale while in movement.
Stretched out on floor with stomach down, place
elbows parallel to shoulders and raise torso up. Keep
arms bent and only raise torso off the ground as far as
the navel.
Lying on stomach with hands beneath the body, raise
legs one at a time while tensing buttocks. Repeat with
other leg.
Sit with legs crossed (only one leg should be over the
other) and knees touching the floor.
Standing with feet together, hold hands above the
head with arms outstretched. Exhale and stretch to
the left. Inhale and return to center. Repeat on other
side.
Make a fist around thumb and squeeze. Release
slowly and repeat on other hand.
Sitting with right leg outstretched and the left leg
bend toward the body with the left foot touching
the right leg, stretch head to right knee. Repeat on
other side.
On hands and knees, cross left knee in front of right
knee while sitting back between the heels. Hold heels
with hands.
Lying on back with arms outstretched, place
right foot on left knee and swivel right knee to the left
side of floor. While in movement, turn head to left
side. Repeat on opposite side.
Lying on stomach with hands under the body,
squeeze buttocks and lift legs up and outward. Keep
legs straight.
Standing with feet together, inhale while raising arms
straight above the head and clasp hands together.
Exhale while lowering arms.
Kneeling, slide the left leg straight out from behind
and inhale, stretching torso up. Release and repeat on
other side.
Lying on back, inhale and raise legs over head while
keeping hands flat on floor for support.

Boat

Bow
Bridge

C

Camel

Cat
Child
Cobra

Corpse
Dog
Downward Dog

Half Cobra

Half Locust

Half Lotus
Half-Moon

Hand and thumb
squeeze
Head to knee

Hero

Knee down twist

Locust

Mountain

Pigeon

Plow

4028

Name

Description

Posterior
stretch
Rag Doll

Sitting with legs outstretched and feet together, stretch
head to toes.
While standing, exhale and bend over toward toes,
cupping elbows with hands. Breathe deeply.
Sitting with legs outstretched in a V shape, stretch arms
to toes and head to floor.
With back straight, slowly lift shoulder to ear and lower.
Repeat on other side.
Lying on back, lift legs up and support back with hands.
Slowly angle legs over head and then extend upward.
Lying on stomach with elbows parallel to shoulders and
palms on the ground, push torso up and look upward.
Press fingertips together and move palms in and out.
Sitting with right foot crossed over left leg and right leg
held with left arm. Twist while supporting body with
right hand on the floor. Repeat on other side.
Inhale and step into V position, stretching arms out and
then down toward floor.
Standing with arms at sides, inhale and raise arms in
front. Exhale and swing arms to back.
While standing, place one foot on the opposite thigh and
outstretch arms above the head. Hold hands above with
index fingers straight and the remaining fingers clasped.
With arms parallel to floor and legs outstretched, turn
one foot out and stretch to that side, keeping arms
straight. Repeat on other side.
Lying on stomach with hands down near the chest, lift
torso off the floor while raising on toes. Hands should
raise, but remain palms down. Arch back slightly.
Raise arms over head with palms together and lunge
forward with one foot, keeping thigh parallel to the
ground.
With arms straight out and parallel to the ground and
legs in V, turn one foot out and lunge to the side, keeping
hips straight.
Sitting on heels, round torso to the ground with forehead
to the floor while stretching arms overhead. Inhale while
in movement and exhale while lowering arms.

Seated angle
Shoulder
crunch
Shoulder
stand
Sphinx
Spider
Spinal twist

Standing
angle
Standing yoga
mudra
Tree

Triangle

Upward Dog

Warrior I

Warrior II

Yoga Mudra

mind in tune with the body. The other four deal with
different stages of meditation. There are six major
types of yoga, all with the same goals of health and
harmony but with varying techniques: hatha, raja,
karma, bhakti, jnana, and tantra yoga. Hatha yoga
is the most commonly practiced branch of yoga in
America, and it is a highly developed system of nearly
200 physical postures, movements and breathing
techniques designed to tune the body to its optimal
health. The yoga philosophy believes the breath to be
the most important facet of health, as the breath is the
largest source of prana, or life force, and hatha yoga
utilizes pranayama, which literally means the science
or control of breathing. Hatha yoga was originally
developed as a system to make the body strong and
healthy enough to enable mental awareness and spiritual enlightenment.
GALE ENCYCLOPEDIA OF MEDICINE

Yoga
Yoga is a system that benefits the body, mind, and spirit by teaching self-control through a series of postures and exercises as
well as through breathing, relaxation, and meditation techniques. (Illustration by Electronic Illustrators Group.)

There are several different schools of hatha yoga
in America; the two most prevalent ones are Iyengar
and ashtanga yoga. Iyengar yoga was founded by
B.K.S. Iyengar, who is widely considered as one of
the great living innovators of yoga. Iyengar yoga puts
strict emphasis on form and alignment, and uses
traditional hatha yoga techniques in new manners
and sequences. Iyengar yoga can be good for physical
therapy because it allows the use of props like straps
and blocks to make it easier for some people to get
into the yoga postures. Ashtanga yoga can be a more
vigorous routine, using a flowing and dance-like
sequence of hatha postures to generate body heat,
which purifies the body through sweating and deep
breathing.
The other types of yoga show some of the remaining ideas which permeate yoga. Raja yoga strives to
bring about mental clarity and discipline through
meditation, simplicity, and non-attachment to worldly
things and desires. Karma yoga emphasizes charity,
service to others, non-aggression and non-harming as
means to awareness and peace. Bhakti yoga is the path
of devotion and love of God, or Universal Spirit.
Jnana yoga is the practice and development of knowledge and wisdom. Finally, tantra yoga is the path of
self-awareness through religious rituals, including
awareness of sexuality as sacred and vital.
A typical hatha yoga routine consists of a
sequence of physical poses, or asanas, and the
sequence is designed to work all parts of the body,
with particular emphasis on making the spine supple
and healthy and increasing circulation. Hatha yoga
asanas utilize three basic movements: forward bends,
backward bends, and twisting motions. Each asana is
named for a common thing it resembles, like the sun
salutation, cobra, locust, plough, bow, eagle, tree, and
4030

the head to knee pose, to name a few. Each pose has
steps for entering and exiting it, and each posture
requires proper form and alignment. A pose is held
for some time, depending on its level of difficulty and
one’s strength and stamina, and the practitioner is also
usually aware of when to inhale and exhale at certain
points in each posture, as breathing properly is
another fundamental aspect of yoga. Breathing should
be deep and through the nose. Mental concentration
in each position is also very important, which
improves awareness, poise and posture. During a
yoga routine there is often a position in which to perform meditation, if deep relaxation is one of the goals
of the sequence.
Yoga routines can take anywhere from 20 minutes
to two or more hours, with one hour being a good time
investment to perform a sequence of postures and a
meditation. Some yoga routines, depending on the
teacher and school, can be as strenuous as the most
difficult workout, and some routines merely stretch
and align the body while the breath and heart rate
are kept slow and steady. Yoga achieves its best results
when it is practiced as a daily discipline, and yoga can
be a life-long exercise routine, offering deeper and
more challenging positions as a practitioner becomes
more adept. The basic positions can increase a person’s strength, flexibility and sense of well-being
almost immediately, but it can take years to perfect
and deepen them, which is an appealing and stimulating aspect of yoga for many.
Yoga is usually best learned from a yoga teacher
or physical therapist, but yoga is simple enough that
one can learn the basics from good books on the
subject, which are plentiful. Yoga classes are generally
inexpensive, averaging around 10 dollars per class,
and students can learn basic postures in just a few
GALE ENCYCLOPEDIA OF MEDICINE

Preparations
Yoga can be performed by those of any age and
condition, although not all poses should be attempted
by everyone. Yoga is also a very accessible form of
exercise; all that is needed is a flat floor surface large
enough to stretch out on, a mat or towel, and enough
overhead space to fully raise the arms. It is a good
activity for those who can’t go to gyms, who don’t like
other forms of exercise, or have very busy schedules.
Yoga should be done on an empty stomach, and teachers recommend waiting three or more hours after
meals. Loose and comfortable clothing should be
worn.

Precautions
People with injuries, medical conditions, or spinal
problems should consult a doctor before beginning
yoga. Those with medical conditions should find a
yoga teacher who is familiar with their type of problem
and who is willing to give them individual attention.
Pregnant women can benefit from yoga, but should
always be guided by an experienced teacher. Certain
yoga positions should not be performed with a fever,
or during menstruation.
Beginners should exercise care and concentration
when performing yoga postures, and not try to stretch
too much too quickly, as injury could result. Some
advanced yoga postures, like the headstand and full
lotus position, can be difficult and require strength,
flexibility, and gradual preparation, so beginners
should get the help of a teacher before attempting
them.
Yoga is not a competive sport; it does not matter
how a person does in comparison with others, but how
aware and disciplined one becomes with one’s own
body and limitations. Proper form and alignment
should always be maintained during a stretch or posture, and the stretch or posture should be stopped
when there is pain, dizziness, or fatigue. The mental
component of yoga is just as important as the physical
postures. Concentration and awareness of breath
should not be neglected. Yoga should be done with
an open, gentle, and non-critical mind; when one
stretches into a yoga position, it can be thought of
accepting and working on one’s limits. Impatience,
GALE ENCYCLOPEDIA OF MEDICINE

Yoga

classes. Many YMCAs, colleges, and community
health organizations offer beginning yoga classes as
well, often for nominal fees. If yoga is part of a physical therapy program, its cost can be reimbursed by
insurance.

KEY TERMS
Asana—A position or stance in yoga.
Dyana—The yoga term for meditation.
Hatha yoga—Form of yoga using postures, breathing methods and meditation.
Meditation—Technique of concentration for relaxing the mind and body.
Pranayama—Yoga breathing techniques.
Yogi (female, yogini)—A trained practitioner of
yoga.

self-criticism and comparing oneself to others will
not help in this process of self-knowledge. While performing the yoga of breathing (pranayama) and meditation (dyana), it is best to have an experienced
teacher, as these powerful techniques can cause dizziness and discomfort when done improperly.

Side effects
Some people have reported injuries by performing
yoga postures without proper form or concentration,
or by attempting difficult positions without working
up to them gradually or having appropriate supervision. Beginners sometimes report muscle soreness and
fatigue after performing yoga, but these side effects
diminish with practice.

Research and general acceptance
Although yoga originated in a culture very different from that of modern America, it has been accepted
and its practice has spread relatively quickly. Many
yogis are amazed at how rapidly yoga’s popularity has
spread in the United States and Canada, considering
the legend that it was passed down secretly by handfuls
of adherents for many centuries.
There can still be found some resistance to yoga,
for active and busy Americans sometimes find it hard
to believe that an exercise program that requires them
to slow down, concentrate, and breathe deeply can be
more effective than lifting weights or running.
However, ongoing research in top medical schools is
showing yoga’s effectiveness for overall health and for
specific problems, making it an increasingly acceptable health practice.
The growing acceptability of yoga as an alternative therapy for certain disorders or conditions is
4031

Yoga

reflected in the fact that the National Center for
Complementary
and
Alternative
Medicine
(NCCAM) is conducting a series of clinical trials of
ypga. As of the summer of 2004, NCCAM has five
clinical trials in progress, evaluating yoga as a treatment for chronic low back pain; insomnia; depression
in patients diagnosed with HIV infection; and shortness of breath in chronic obstructive pulmonary disease (COPD). The fifth clinical trial is an evaluation of
yoga in improving attention span in aging and multiple sclerosis.
Resources
BOOKS

Ansari, Mark, and Liz Lark. Yoga for Beginners. New York:
Harper, 1999.
Pelletier, Kenneth R., MD. The Best Alternative Medicine,
Chapter 10, ‘‘Ayurvedic Medicine and Yoga: From
Buddha to the Millennium.’’ New York: Simon &
Schuster, 2002.
PERIODICALS

Bielory, L., J. Russin, and G. B. Zuckerman. ‘‘Clinical
Efficacy, Mechanisms of Action, and Adverse Effects of
Complementary and Alternative Medicine Therapies
for Asthma.’’ Allergy and Asthma Proceedings 25
(September-October 2004): 283–291.
Engebretson, J. ‘‘Culture and Complementary Therapies’’
Complementary Therapies in Nursing and Midwifery 8
(November 2002): 177–184.
Gerritsen, A. A., M. C. de Krom, M. A. Struijs, et al.
‘‘Conservative Treatment Options for Carpal Tunnel
Syndrome: A Systematic Review of Randomized
Controlled Trials.’’ Journal of Neurology 249 (March
2002): 272–280.
Kronenberg, F., and A. Fugh-Berman. ‘‘Complementary
and Alternative Medicine for Menopausal Symptoms:
A Review of Randomized, Controlled Trials.’’ Annals
of Internal Medicine 137 (November 19, 2002): 805–813.
Lee, S. W., C. A. Mancuso, and M. E. Charlson.
‘‘Prospective Study of New Participants in a
Community-Based Mind-Body Training Program.’’

4032

Journal of General Internal Medicine 19 (July 2004):
760–765.
Manocha, R., G. B. Marks, P. Kenchington, et al. ‘‘Sahaja
Yoga in the Management of Moderate to Severe
Asthma: A Randomized Controlled Trial.’’ Thorax 57
(February 2002): 110–115.
Raub, J. A. ‘‘Psychophysiologic Effects of Hatha Yoga on
Musculoskeletal and Cardiopulmonary Function:
A Literature Review.’’ Journal of Alternative and
Complementary Medicine 8 (December 2002): 797–812.
Tonini, G. ‘‘Dysmenorrhea, Endometriosis and
Premenstrual Syndrome’’ [in Italian] Minerva
Pediatrica 54 (December 2002): 525–538.
Vyas, R., and N. Dikshit. ‘‘Effect of Meditation on
Respiratory System, Cardiovascular System and Lipid
Profile.’’ Indian Journal of Physiology and
Pharmacology 46 (October 2002): 487–491.
Yoga International Magazine. R.R. 1 Box 407, Honesdale,
PA 18431. <http://www.yimag.com>.
Yoga Journal. P.O. Box 469088, Escondido, CA 92046.
<http://www.yogajournal.com>.
ORGANIZATIONS

American Yoga Association. <http://
www.americanyogaassociation.org>.
International Association of Yoga Therapists (IAYT). 4150
Tivoli Ave., Los Angeles, CA 90066.
National Center for Complementary and Alternative
Medicine (NCCAM) Clearinghouse. P. O. Box 7923.
Gaitherburg, MD 20898. (888) 644-6226. Fax: (866)
464-3616. <http://nccam.nih.gov>.
Yoga Research and Education Center (YREC). 2400A
County Center Drive, Santa Rosa, CA 95403. (707)
566-0000. <http://www.yrec.org>.
OTHER

NCCAM Yoga Clinical Trials. <http://nccam.nih.gov/
clinicaltrials/yoga.htm>.

Douglas Dupler, MA
Rebecca J. Frey, PhD

"Yuppie flu" see Chronic fatigue syndrome

GALE ENCYCLOPEDIA OF MEDICINE

Z
Zenker’s diverticulum see Esophageal
pouches
Zidovudine see Antiretroviral drugs
Zinc deficiency see Mineral deficiency
Zinc excess see Mineral toxicity
Zolpidem see Anti-insomnia drugs

Zoonosis
Definition
Zoonosis, also called zoonotic disease refers to
diseases that can be passed from animals, whether
wild or domesticated, to humans.

tick, feeds on an infected animal, then feeds on a
human. In the process, the insect transfers the infecting organism.
The Centers for Disease Control (CDC) in
Atlanta have said that most emerging diseases
around the world are zoonotic. The director of the
CDC has said that 11 of the last 12 emerging infections in the world with serious health consequences
has probably arisen from animal sources. Wild animal trade occurs across countries and many people
take in wild animals as domestic pets. However, pet
shops and food markets are not properly testing for
diseases and parasites that can cause harm to
humans and other animals.
Some zoonotic diseases are well known, such as
rats (plague), deer tick (Lyme disease). Others are not
as well known. For example, elephants may develop
tuberculosis, and spread it to humans.

Description
Although many diseases are species specific,
meaning that they can only occur in one animal species, many other diseases can be spread between different animal species. These are infectious diseases,
caused by bacteria, viruses, or other disease causing
organisms that can live as well in humans as in other
animals.
There are different methods of transmission for
different diseases. In some cases, zoonotic diseases
are transferred by direct contact with infected animals, much as being near an infected human can
cause the spread of an infectious disease. Other diseases are spread by drinking water that contains the
eggs of parasites. The eggs enter the water supply
from the feces of infected animals. Still others are
spread by eating the flesh of infected animals.
Tapeworms are spread this way. Other diseases are
spread by insect vectors. An insect, such as a flea or
GALE ENCYCLOPEDIA OF MEDICINE

Causes and symptoms
The following is a partial list of animals and the
diseases that they may carry. Not all animal carriers
are listed, nor are all the diseases that the various
species may carry.


Bats are important rabies carriers, and also carry
several other viral diseases that can affect humans.



Cats may carry the causative organisms for plague,
anthrax, cowpox, tapeworm, and many bacterial
infections.



Dogs may carry plague, tapeworm, rabies, Rocky
Mountain Spotted Fever, and Lyme disease.



Horses may carry anthrax, rabies, and Salmonella
infections.



Cattle may carry the organisms that cause anthrax,
European tick-borne encephalitis, rabies, tapeworm,
4033

Zoonosis

Salmonella infections and many bacterial and viral
diseases.


Pigs are best known for carrying tapeworm, but may
also carry a large number of other infections including anthrax, influenza, and rabies.



Sheep and goats may carry rabies, European tickborne encephalitis, Salmonella infections, and many
bacterial and viral diseases.



Rabbits may carry plague and Q-Fever.



Birds may carry Campylobacteriosis, Chlamydia
psittaci, Pasteurella multocida, Histoplasma capsulatum, Salmonellosis, and others.

Zoonotic diseases may be spread in different
ways. Tapeworms can often spread to humans when
people eat the infected meat of cattle, and swine. Other
diseases are transferred by insect vectors, often bloodfeeding insects that carry the cause of the disease from
one animal to another.

Diagnosis
Diagnosis of the disease is made in the usual
manner, by identifying the infecting organism.
Each disease has established symptoms and tests.
Identifying the carrier may be easy, or may be more
difficult when the cause is a fairly common infection.
For example, tapeworms are usually species specific.
Cattle, pigs, and fish all carry different species of
tapeworms, although all can be transmitted to
humans who eat undercooked meat containing live
tapeworm eggs. Once the tapeworm has been identified, it is easy to tell which species the tapeworm
came from.
Other zoonotic infections may be harder to identify. Sometimes the infection is fairly common among
both humans and animals, and it is impossible to tell.
Snakes may carry the bacteria Escherichia coli and
Proteus vulgaris, but since these bacteria are already
common among humans, it would be difficult to trace
infections back to snakes.
Because of increased trade between nations, and
changes in animal habitats, there are often new zoonotic diseases. These may be found in animals transported from one nation to another, bringing with them
new diseases. In some cases, changes in the environment lead to changes in the migratory habits of animal
species, bringing new infections.

Treatment
Treatment is the established treatment for the
specific infection.
4034

KEY TERMS
Anthrax—A diease of wam blooded animals, particularly cattle and sheep, transmissable to
humans. The disease causes severe skin and lung
damage.
Bovine spongiform encephalopathy—A progressive, fatal disease of the nervous system of domestic
animals. It is transmitted by eating infected food.
Also known as Mad Cow disease.
Lyme disease—An acute disease which is usually
marked by skin rash, fever, fatigue and chills. Left
untreated, it may cause heart and nervous system
damage.
Q-Fever—A disease that is marked by high fever,
chills and muscle pain. It is seen in North America,
Europe, and parts of Africa. It may be spread by
drinking raw milk, or by tick bites.
Zoonotic—A disease which can be spread from
animals to humans.

Prevention
Prevention of zoonotic infections may take different forms, depending on the nature of the carrier and
the infection.
Some zoonotic infections can be avoided by
immunizing the animals that carry the disease. Pets
and other domestic animals should have rabies vaccinations, and wild animals are immunized with an oral
vaccine that is encased in a suitable bait. In some
places, the bait is dropped by airplane over the range
of the potential rabies carrier. When the animal eats
the bait, they also ingest the oral vaccine, thereby
protecting them from rabies, and reducing the risk of
spread of the disease. This method has been used to
protect foxes, coyotes, and other wild animals.
Many zoonotic diseases that are passed by eating
the meat of infected animals can be prevented by
proper cooking of the infected meat. Tapeworm infestations can be prevented by cooking, and Salmonella
infections from chickens and eggs can be prevented by
being sure that both the meat and the eggs are fully
cooked.
For other zoonotic diseases, programs are in place
to eliminate the host, or the vector that spreads the
disease. Plague is prevented by elimination of the
rats—a common source of the infection—and of fleas
that carry the disease from rats to humans. Efforts
GALE ENCYCLOPEDIA OF MEDICINE

‘‘When man’s best friend isn’t.’’ Mother Earth News
June-July 2000.
‘‘Zoonoses.’’ Agricultural Research February 2000.
‘‘Zoonotic Diseases.’’ Medical Laboratory Observer March
2004: 12.
‘‘The zoonotic threat: Curbing pet-to-people infections.’’
Dog World October 1999.

Other means of prevention simply rely on care.
People living in areas where Lyme disease is common
are warned to take precautions against the bite of the
deer tick, which transfers the disease. These precautions include not walking in tall grass, not walking
bare legged, and wearing light-colored clothing so
that the presence of the dark ticks can be readily seen.

ORGANIZATIONS

Resources
PERIODICALS

‘‘CDC Improves Monitoring of Outbreaks.’’ American
Medical News January 24, 2000.

GALE ENCYCLOPEDIA OF MEDICINE

American Association of Zoo Keepers (AAZK). Topeka
Zoological Park 3601 SW 29th St., Ste. 133 Topeka, KS
66614-2054.
National Animal Disease Center Zoonotic Research Unit.
2300 Dayton Ave. PO Box 70 Ames, IA 50010.

Samuel D. Uretsky, PharmD
Teresa G. Odle

Zoonotic infections see Zoonosis
Zygomycosis see Mucormycosis

4035

Zoonosis

around the world to control bovine spongiform encephalitis, better known as Mad Cow disease, have
focused on the destruction of infected cattle to prevent
spread of the disease. Regulations on the makeup of the
cattle feed to ensure safety and prevent the disease have
helped curb its spread.


Neurodevelopmental Disorders 

The neurodevelopmental disorders 
are a group of conditions with onset 
in the developmental 
period. The disorders typically manifest 
early in development, often before the 
child enters school, and are characterized by developmental 
deficits or differences in brain 
processes that 
produce impairments of personal, social, academic, or occupational 
functioning. 
The range of developmental 
deficits or differences varies from 
very specific limitations of 
learning or control 
of executive functions to global 
impairments of social 
skills or intellectual 
ability. Once thought 
to be categorically defined, more recent 
dimensional 
approaches to 
measurement 
of the symptoms demonstrate a range of severity, often without 
a very clear 
boundary with typical 
development. Diagnosis of a disorder thus requires the presence of both 
symptoms and impaired function. 


The neurodevelopmental 
disorders frequently co-occur with one another; 
for example, 
individuals with autism 
spectrum 
disorder often have intellectual 
developmental 
disorder 
(intellectual 
disability), and many children with attention-deficit/hyperactivity disorder (ADHD) 
also have a specific learning disorder. The neurodevelopmental 
disorders also frequently co-
occur with other mental 
and behavioral 
disorders with onset 
in childhood (e.g., communication 
disorders and autism 
spectrum 
disorder may be associated with anxiety disorders; 
ADHD with 
oppositional 
defiant 
disorder; 
tics with obsessive-compulsive disorder). For some 
neurodevelopmental 
disorders, the clinical 
presentation includes behaviors that 
are more frequent 
or intense when compared with those of normal 
children of the same developmental 
age and 
gender, as well 
as deficits and delays in achieving expected milestones. For example, autism 
spectrum 
disorder is diagnosed only when the characteristic deficits of social 
communication are 
accompanied by excessively repetitive behaviors, restricted interests, and insistence on 
sameness. 


Intellectual 
developmental 
disorder is characterized by deficits in general 
mental 
abilities, 
such as reasoning, problem 
solving, planning, abstract 
thinking, judgment, academic learning, 
and learning from 
experience. The deficits result 
in impairments of adaptive functioning, such 
that 
the individual 
fails to meet 
standards of personal 
independence and social 
responsibility in 
one or more aspects of daily life, including communication, social 
participation, academic or 
occupational 
functioning, and personal 
independence at 
home or in community settings. Global 
developmental 
delay, as its name implies, is diagnosed when an individual 
fails to meet 
expected 
developmental 
milestones in several 
areas of intellectual 
functioning. The diagnosis is used for 
individuals younger than 5 years who are unable to undergo systematic assessments of 
intellectual 
functioning, and thus the clinical 
severity level 
cannot 
be reliably assessed. 
Intellectual 
developmental 
disorder may result 
from 
an acquired insult 
during the developmental 
period from, for example, a severe head injury, in which case a neurocognitive disorder also may 
be diagnosed. 


The communication disorders include language disorder, speech sound disorder, social 



(pragmatic) communication disorder, and childhood-onset 
fluency disorder (stuttering). The first 
three disorders are characterized by deficits in the development 
and use of language, speech, and 
social 
communication, respectively. Social 
communication disorder is characterized by deficits 
in both verbal and nonverbal communication skills that result in 


36 


social 
impairment 
and are not 
better explained by low abilities in structural 
language, 
intellectual 
developmental 
disorder, or autism 
spectrum 
disorder. Childhood-onset 
fluency 
disorder is characterized by disturbances of the normal 
fluency and motor production of speech, 
including repetitive sounds or syllables, prolongation of consonants or vowel 
sounds, broken 
words, blocking, or words produced with an excess of physical 
tension. Like other 
neurodevelopmental 
disorders, communication disorders begin early in life and may produce 
lifelong functional impairments. 


Autism 
spectrum 
disorder is characterized by persistent 
deficits in social 
communication and 
social 
interaction across multiple contexts, including deficits in social 
reciprocity, nonverbal 
communicative behaviors used for social 
interaction, and skills in developing, maintaining, and 
understanding relationships. In addition to the social 
communication deficits, the diagnosis of 
autism 
spectrum 
disorder requires the presence of restricted, repetitive patterns of behavior, 
interests, or activities. Because symptoms change with development 
and may be masked by 
compensatory mechanisms, the diagnostic criteria may be met 
based on historical 
information, 
although the current presentation must cause significant impairment. 


Within the diagnosis of autism 
spectrum 
disorder, individual 
clinical 
characteristics are noted 
through the use of specifiers (with or without 
accompanying intellectual 
impairment; 
with or 
without 
accompanying structural 
language impairment; 
associated with a known genetic or other 
medical 
condition or environmental 
factor; 
associated with a neurodevelopmental, mental, or 
behavioral 
problem), as well 
as specifiers that 
describe the severity of autistic symptoms. These 
specifiers provide clinicians with an opportunity to individualize the diagnosis and communicate 
a richer clinical 
description of the affected individuals. For example, many individuals 
previously diagnosed with Asperger s disorder would now receive a diagnosis of autism 
spectrum disorder without language or intellectual impairment. 


ADHD is a neurodevelopmental 
disorder defined by impairing levels of inattention, 
disorganization, and/or hyperactivity-impulsivity. Inattention and disorganization entail 
inability 
to stay on task, seeming not 
to listen, and losing materials necessary for tasks, at 
levels that 
are 
inconsistent 
with age or developmental 
level. Hyperactivity-impulsivity entails overactivity, 
fidgeting, inability to stay seated, intruding into other people s activities, and inability to wait  
symptoms that 
are excessive for age or developmental 
level. In childhood, ADHD frequently 
overlaps with disorders that 
are often considered to be  externalizing disorders,  such as 
oppositional 
defiant 
disorder and conduct 
disorder. ADHD often persists into adulthood, with 
resultant impairments of social, academic, and occupational functioning. 


Specific learning disorder, as the name implies, is diagnosed when there are specific deficits 
in an individual s ability to perceive or process information for learning academic skills 
efficiently and accurately. This neurodevelopmental 
disorder first 
manifests during the years of 
formal 
schooling and is characterized by persistent 
and impairing difficulties with learning 
foundational 
academic skills in reading, writing, and/or math. The individual s performance of 



the affected academic skills is well 
below average for age, or acceptable performance levels are 
achieved only with extraordinary effort. Specific learning disorder may occur in individuals 
identified as intellectually gifted and manifest 
only when the learning demands or assessment 
procedures (e.g., timed tests) pose barriers that 
cannot 
be overcome by their innate intelligence 
and compensatory strategies. For all 
individuals, specific learning disorder can produce lifelong 
impairments in activities dependent on the skills, including occupational performance. 


The neurodevelopmental 
motor disorders include developmental 
coordination disorder, 
stereotypic movement 
disorder, and tic disorders. Developmental 
coordination disorder is 
characterized by deficits in the acquisition and execution of coordinated motor skills and is 
manifested by clumsiness and slowness or inaccuracy of performance of 


37 


motor skills that 
cause interference with activities of daily living. Stereotypic movement 
disorder is diagnosed when an individual 
has repetitive, seemingly driven, and apparently 
purposeless motor behaviors, such as hand flapping, body rocking, head banging, self-biting, or 
hitting. The movements interfere with social, academic, or other activities. If the behaviors cause 
self-injury, this should be specified as part 
of the diagnostic description. Tic disorders are 
characterized by the presence of motor or vocal 
tics, which are sudden, rapid, recurrent, 
nonrhythmic, stereotyped motor movements or vocalizations. The duration, presumed etiology, 
and clinical 
presentation define the specific tic disorder that 
is diagnosed: 
Tourette s disorder, 
persistent 
(chronic) motor or vocal 
tic disorder, provisional 
tic disorder, other specified tic 
disorder, and unspecified tic disorder. Tourette s disorder is diagnosed when the individual 
has 
multiple motor and vocal 
tics that 
have been present 
for at 
least 
1 year and that 
have a waxing-
waning symptom course. 


The use of specifiers for the neurodevelopmental 
disorder diagnoses enriches the clinical 
description of the individual s clinical 
course and current 
symptomatology. These include the 
following: 
Severity specifiers are available for intellectual 
developmental 
disorder, autism 
spectrum 
disorder, ADHD, specific learning disorder, and stereotypic movement 
disorder. 
Specifiers indicative of current 
symptomatology are available for ADHD, specific learning 
disorder, and persistent 
motor or vocal 
tic disorder. Autism 
spectrum 
disorder and stereotypic 
movement 
disorder also include the specifier  associated with a known genetic or other medical 
condition or environmental 
factor.  This specifier gives clinicians an opportunity to document 
factors that 
may have played a role in the etiology of the disorder, as well 
as those that 
might 
affect the clinical course. 


Intellectual 
Developmental 
Disorders 


Intellectual 
Developmental 
Disorder (Intellectual 
Disability) 



Diagnostic Criteria 


Intellectual developmental disorder (intellectual disability) is a 
disorder with 
onset 
during 
the 
developmental period 
that 
includes both 
intellectual and 
adaptive 
functioning 
deficits in 
conceptual, 
social, 
and 
practical domains. 
The 
following 
three 
criteria 
must 
be 
met: 


A. 
Deficits in 
intellectual functions, 
such 
as reasoning, 
problem solving, 
planning, 
abstract 
thinking, 
judgment, 
academic learning, 
and 
learning 
from experience, 
confirmed 
by both 
clinical assessment 
and 
individualized, 
standardized 
intelligence 
testing. 
B. 
Deficits in 
adaptive 
functioning 
that 
result 
in 
failure 
to 
meet 
developmental and 
sociocultural standards for personal independence 
and 
social responsibility. 
Without 
ongoing 
support, 
the 
adaptive 
deficits limit 
functioning 
in 
one 
or more 
activities of 
daily life, 
such 
as communication, 
social participation, 
and 
independent 
living, 
across multiple 
environments, 
such 
as home, 
school, 
work, 
and 
community. 
C. 
Onset 
of 
intellectual and 
adaptive 
deficits during 
the 
developmental period. 
38 


Note: 
The 
term intellectual developmental disorder 
is used 
to 
clarify its relationship 
with 
the 
WHO 
ICD-11 
classification 
system, 
which 
uses the 
term Disorders of 
Intellectual Development. 
The 
equivalent 
term intellectual disability 
is placed 
in 
parentheses for continued 
use. 
The 
medical and 
research 
literature 
use 
both 
terms, 
while 
intellectual disability is the 
term in 
common 
use 
by educational and 
other 
professions, 
advocacy groups, 
and 
the 
lay public. 
In 
the 
United 
States, 
Public Law 
111-256 
(Rosa s Law) changed 
all references to 
 mental retardation  in 
federal laws 
to 
 intellectual disability.  


Specify 
current 
severity (see 
Table 
1): 


F70 
Mild 


F71 
Moderate 


F72 
Severe 


F73 
Profound 


39 


TABLE 
1 
Severity 
levels 
for intellectual 
developmental 
disorder (intellectual 
disability) 


Severity 
level 
Conceptual 
domain 
Social 
domain 
Practical 
domain 
Mild 
For preschool children, there may be 
Compared with typically developing 
The individual may function age



no obvious conceptual differences.age-mates, the individual isappropriately in personal care.
For school-age children and adults, 
immature in social interactions. 
Individuals need some support 
there are difficulties in learning 
For example, there may be 
with complex daily living tasks in 
academic skills involving reading, 
difficulty in accurately perceiving 
comparison to peers. In adulthood, 
writing, arithmetic, time, or 
peers  social cues. 
supports typically involve grocery 
money, with support needed in one 
Communication, conversation, and 
shopping, transportation, home 
or more areas to meet age-related 
language are more concrete or 
and child-care organizing, 
expectations. In adults, abstract 
immature than expected for age. 
nutritious food preparation, and 
thinking, executive function (i.e., 
There may be difficulties 
banking and money management. 
planning, strategizing, priority 
regulating emotion and behavior in 
Recreational skills resemble those 
setting, and cognitive flexibility), 
age-appropriate fashion; these 
of age-mates, although judgment 
and short-term memory, as well as 
difficulties are noticed by peers in 
related to well-being and 
functional use of academic skills 
social situations. There is limited 
organization around recreation 
(e.g., reading, money 
understanding of risk in social 
requires support. In adulthood, 
management), are impaired. There 
situations; social judgment is 
competitive employment is often 
is a somewhat concrete approach 
immature for age, and the person 
seen in jobs that do not emphasize 
to problems and solutions 
is at risk of being manipulated by 
conceptual skills. Individuals 
compared with age-mates. 
others (gullibility). 
generally need support to make 
health care decisions and legal 
decisions, and to learn to perform 
a skilled vocation competently. 
Support is typically needed to raise 
a family. 
40 
All through development, the 
individual s conceptual skills lag 
The individual shows marked 
differences from peers in social 
The individual can care for personal 
needs involving eating, dressing, 
Moderate 
markedly behind those of peers. 
For preschoolers, language and 
preacademic skills develop slowly. 
For school-age children, progress 
in reading, writing, mathematics, 
and understanding of time and 
money occurs slowly across the 
school years and is markedly 
limited compared with that of 
peers. For adults, academic skill 
development is typically at an 
elementary level, and support is 
required for all use of academic 
skills in work and personal life. 
Ongoing assistance on a daily 
basis is needed to complete 
conceptual tasks of day-to-day life, 
and others may take over these 
responsibilities fully for the 
individual. 
and communicative behavior 
across development. Spoken 
language is typically a primary 
tool for social communication but 
is much less complex than that of 
peers. Capacity for relationships is 
evident in ties to family and 
friends, and the individual may 
have successful friendships across 
life and sometimes romantic 
relations in adulthood. However, 
individuals may not perceive or 
interpret social cues accurately. 
Social judgment and decision-
making abilities are limited, and 
caretakers must assist the person 
with life decisions. Friendships 
with typically developing peers are 
often affected by communication 
or social limitations. Significant 
social and communicative support 
is needed in work settings for 
success. 
elimination, and hygiene as an 
adult, although an extended period 
of teaching and time is needed for 
the individual to become 
independent in these areas, and 
reminders may be needed. 
Similarly, participation in all 
household tasks can be achieved 
by adulthood, although an 
extended period of teaching is 
needed, and ongoing supports will 
typically occur for adult-level 
performance. Independent 
employment in jobs that require 
limited conceptual and 
communication skills can be 
achieved, but considerable support 
from coworkers, supervisors, and 
others is needed to manage social 
expectations, job complexities, and 
ancillary responsibilities such as 
scheduling, transportation, health 
benefits, and money management. 
A variety of recreational skills can 
be developed. These typically 
require additional supports and 
learning opportunities over an 
extended period of time. 
Maladaptive behavior is present in 
a significant minority and causes 
social problems. 
41 
Attainment of conceptual skills is 
Spoken language is quite limited in 
The individual requires support for 
Severe 
limited. The individual generally 
has little understanding of written 
language or of concepts involving 
numbers, quantity, time, and 
terms of vocabulary and grammar. 
Speech may be single words or 
phrases and may be supplemented 
through augmentative means. 
all activities of daily living, 
including meals, dressing, bathing, 
and elimination. The individual 
requires supervision at all times. 



money. Caretakers provide 
Speech and communication are 
The individual cannot make 
extensive supports for problemfocused on the here and now 
responsible decisions regarding 
solving throughout life. 
within everyday events. Language 
is used for social communication 
more than for explication. 
Individuals understand simple 
speech and gestural 
communication. Relationships 
with family members and familiar 
others are a source of pleasure andhelp. 
well-being of self or others. In 
adulthood, participation in tasks at 
home, recreation, and work 
requires ongoing support and 
assistance. Skill acquisition in all 
domains involves long-term 
teaching and ongoing support. 
Maladaptive behavior, including 
self-injury, is present in asignificant minority. 
Profound 
Conceptual skills generally involve 
the physical world rather than 
symbolic processes. The individual 
may use objects in goal-directed 
fashion for self-care, work, and 
recreation. Certain visuospatial 
skills, such as matching and 
sorting based on physical 
characteristics, may be acquired. 
However, co-occurring motor and 
sensory impairments may prevent 
functional use of objects. 
The individual has very limited 
understanding of symbolic 
communication in speech or 
gesture. He or she may understand 
some simple instructions or 
gestures. The individual expresses 
his or her own desires and 
emotions largely through 
nonverbal, nonsymbolic 
communication. The individual 
enjoys relationships with well-
known family members, 
caretakers, and familiar others, and 
initiates and responds to social 
interactions through gestural and 
emotional cues. Co-occurring 
sensory and physical impairments 
may prevent many social 
activities. 
The individual is dependent on others 
for all aspects of daily physical 
care, health, and safety, although 
he or she may be able to 
participate in some of these 
activities as well. Individuals 
without severe physical 
impairments may assist with some 
daily work tasks at home, like 
carrying dishes to the table. Simple 
actions with objects may be the 
basis of participation in some 
vocational activities with high 
levels of ongoing support. 
Recreational activities may 
involve, for example, enjoyment in 
listening to music, watching 
movies, going out for walks, or 
participating in water activities, all 
with the support of others. Co-
occurring physical and sensory 
impairments are frequent barriers 
to participation (beyond watching) 
in home, recreational, and 
vocational activities. Maladaptive 
behavior is present in a significant 
minority. 


Specifiers 


The various levels of severity are defined on the basis of adaptive functioning, and not 
IQ scores, 
because it 
is adaptive functioning that 
determines the level 
of supports required. Moreover, IQ 
measures are less valid in the lower end of the IQ range. 


Diagnostic Features 


The essential 
features of intellectual 
developmental 
disorder (intellectual 
disability) are deficits 
in general 
mental 
abilities (Criterion A) and impairment 
in everyday adaptive functioning, in 
comparison to an individual s age-, gender-, and socioculturally matched peers (Criterion B). 
Onset 
is during the developmental 
period (Criterion C). The diagnosis of intellectual 
developmental 
disorder is based on both clinical 
assessment 
and standardized testing of 
intellectual 
functions, standardized neuropsychological 
tests, and standardized tests of adaptive 
functioning. 


Criterion A refers to intellectual 
functions that 
involve reasoning, problem 
solving, planning, 
abstract 
thinking, judgment, learning from 
instruction and experience, and practical 
understanding. Critical 
components include verbal 
comprehension, working memory, perceptual 



reasoning, quantitative reasoning, abstract 
thought, and cognitive efficacy. Intellectual 
functioning is typically measured with individually administered and psychometrically valid, 
comprehensive, and culturally appropriate tests of intelligence. Individuals with intellectual 
developmental 
disorder have scores of approximately two standard deviations or more below the 
population mean, including a margin for measurement 
error (generally   5 points). On tests with 
a standard deviation of 15 and a mean of 100, this involves a score of 65 75 (70   
5). Clinical 
training and judgment are required to interpret test results and assess intellectual performance. 


Factors that 
may affect 
test 
scores include practice effects (i.e., learning from 
repeated 
testing) and the  Flynn effect  (i.e., overly high scores due to out-of-date test 
norms). Invalid 
scores may result 
from 
the use of brief intelligence screening tests or group tests; 
highly 
discrepant 
individual 
subtest 
scores may make an overall 
IQ score invalid. Instruments must 
be 
normed for the individual s sociocultural 
background and native language. Co-occurring 
disorders that 
affect 
communication, language, and/or motor or sensory function may affect 
test 
scores. Individual 
cognitive profiles based on neuropsychological 
testing as well 
as cross-battery 
intellectual 
assessment 
(using multiple IQ or other cognitive tests to create a profile) are more 
useful for understanding intellectual abilities than a single IQ score. 


42 


Such testing may identify areas of relative strengths and weaknesses, an assessment 
important 
for academic and vocational 
planning. IQ test 
scores are approximations of conceptual 
functioning but 
may be insufficient 
to assess reasoning in real-life situations and mastery of 
practical 
tasks. For example, a person with deficits in intellectual 
functioning whose IQ score is 
somewhat 
above 65 75 may nevertheless have such substantial 
adaptive behavior problems in 
social 
judgment 
or other areas of adaptive functioning that 
the person s actual 
functioning is 
clinically comparable to that 
of individuals with a lower IQ score. Thus, clinical 
judgment 
is 
important 
in interpreting the results of IQ tests, and using them 
as the sole criteria for the 
diagnosis of an intellectual developmental disorder is insufficient. 


Deficits in adaptive functioning (Criterion B) refer to how well 
a person meets community 
standards of personal 
independence and social 
responsibility, in comparison to others of similar 
age and sociocultural 
background. Adaptive functioning involves adaptive reasoning in three 
domains: 
conceptual, social, and practical. The conceptual 
(academic) domain 
involves 
competence in memory, language, reading, writing, math reasoning, acquisition of practical 
knowledge, problem 
solving, and judgment 
in novel 
situations, among others. The social domain 
involves awareness of others  thoughts, feelings, and experiences; 
empathy; 
interpersonal 
communication skills; 
friendship abilities; 
and social 
judgment, among others. The practical 
domain 
involves learning and self-management 
across life settings, including personal 
care, job 
responsibilities, money management, recreation, self-management 
of behavior, and school 
and 
work task organization, among others. Intellectual 
capacity, education, motivation, socialization, 
personality features, vocational 
opportunity, cultural 
experience, and coexisting other medical 
conditions or mental disorders influence adaptive functioning. 


Adaptive functioning is assessed using both clinical 
evaluation and individualized, culturally 
appropriate, psychometrically sound measures. Standardized measures are used with 
knowledgeable informants (e.g., parent 
or other family member; 
teacher; 
counselor; 
care 
provider) and the individual 
to the extent 
possible. Additional 
sources of information include 



educational, developmental, medical, and mental 
health evaluations. Scores from 
standardized 
measures and interview sources must 
be interpreted using clinical 
judgment. When standardized 
testing is difficult 
or impossible, because of a variety of factors (e.g., sensory impairment, severe 
problem 
behavior), the individual 
may be diagnosed with unspecified intellectual 
developmental 
disorder. Adaptive functioning may be difficult 
to assess in a controlled setting (e.g., prisons, 
detention centers); 
if possible, corroborative information reflecting functioning outside those 
settings should be obtained. 


Criterion B 
is met 
when at 
least 
one domain of adaptive functioning conceptual, social, or 
practical is sufficiently impaired that 
ongoing support 
is needed in order for the person to 
perform 
adequately across multiple environments, such as home, school, work, and community. 
Criterion C, onset 
during the developmental 
period, refers to recognition that 
intellectual 
and 
adaptive deficits are present during childhood or adolescence. 


A comprehensive evaluation includes an assessment 
of intellectual 
capacity and adaptive 
functioning; 
identification of genetic and nongenetic etiologies; 
evaluation for associated 
medical 
conditions (e.g., cerebral 
palsy, seizure disorder); 
and evaluation for co-occurring 
mental, emotional, and behavioral 
disorders. Components of the evaluation may include basic 
pre-and perinatal 
medical 
history, three-generational 
family pedigree, physical 
examination, 
genetic evaluation (e.g., karyotype or chromosomal 
microarray analysis and testing for specific 
genetic syndromes), and metabolic screening and neuroimaging assessment. 


Associated Features 


Intellectual 
developmental 
disorder is a heterogeneous condition with multiple causes. There 
may be associated difficulties with social 
judgment; 
assessment 
of risk; 
self-management 
of 
behavior, emotions, or interpersonal relationships; or motivation in school or 


43 


work environments. Because of a lack of awareness of risk and danger, accidental 
injury rates 
may be increased. Lack of communication skills may predispose to disruptive and aggressive 
behaviors. Gullibility is often a feature, involving naivet  in social 
situations and a tendency for 
being easily led by others. Gullibility and lack of awareness of risk may result 
in exploitation by 
others and possible victimization, fraud, unintentional 
criminal 
involvement, false confessions, 
and risk for physical 
and sexual 
abuse. These associated features can be important 
in criminal 
cases, including Atkins-type hearings involving the death penalty. 


Beyond deficits in adaptive functioning, individuals also can become distressed about 
their 
intellectual 
limitations. While such distress may not 
always be seen as having an impact 
on 
functioning, distress can represent an important feature of the clinical scenario. 


Prevalence 


Intellectual 
developmental 
disorder has an overall 
general 
population prevalence of 
approximately 10 per 1,000; 
however, the global 
prevalence varies by country and level 
of 
development, being approximately 16 per 1,000 in middle-income countries and 9 per 1,000 in 
high-income countries. The prevalence also varies by age, being higher in youth than in adults. 
In the United States, prevalence per 1,000 population does not 
vary significantly by ethnoracial 
groups. 



Development and Course 


Onset 
of intellectual 
developmental 
disorder is in the developmental 
period. The age and 
characteristic features at 
onset 
depend on the etiology and severity of brain dysfunction. Delayed 
motor, language, and social 
milestones may be identifiable within the first 
2 years of life among 
those with more severe intellectual 
developmental 
disorder, while mild levels may not 
be 
identifiable until 
school 
age when difficulty with academic learning becomes apparent. All 
criteria (including Criterion C) must 
be fulfilled by history or current 
presentation. Some 
children younger than 5 years whose presentation will 
eventually meet 
criteria for intellectual 
developmental disorder have deficits that meet criteria for global developmental delay. 


When intellectual 
developmental 
disorder is associated with a genetic syndrome, there may 
be a characteristic physical 
appearance (e.g., as in Down syndrome). Some syndromes have a 
behavioral 
phenotype, 
which refers to specific behaviors that 
are characteristic of particular 
genetic disorder (e.g., Lesch-Nyhan syndrome). In acquired forms, the onset 
may be abrupt 
following an illness such as meningitis or encephalitis or head trauma occurring during the 
developmental 
period. When intellectual 
developmental 
disorder results from 
a loss of 
previously acquired cognitive skills, as in severe traumatic brain injury, the diagnoses of 
intellectual developmental disorder and of a neurocognitive disorder may both be assigned. 


Although intellectual 
developmental 
disorder is generally nonprogressive, in certain genetic 
disorders (e.g., Rett 
syndrome) there are periods of worsening, followed by stabilization, and in 
others (e.g., Sanfilippo syndrome, Down syndrome) progressive worsening of intellectual 
function in varying degrees. In some cases, the progressive worsening of intellectual 
functioning 
may represent 
the overlay of neurocognitive disorder that 
develops in adulthood (i.e., persons 
with Down syndrome being at 
high risk for developing neurocognitive disorder due to 
Alzheimer s disease in adulthood). In this situation, both diagnoses, intellectual 
developmental 
disorder and neurocognitive disorder, are given. 


The disorder is generally lifelong, although severity levels may change over time. The course 
may be influenced by underlying medical 
or genetic conditions and co-occurring conditions 
(e.g., hearing or visual 
impairments, epilepsy). Early and ongoing interventions may improve 
adaptive functioning throughout 
childhood and adulthood. In some cases, these result 
in 
significant improvement of intellectual functioning, such that the 


44 


diagnosis of intellectual 
developmental 
disorder is no longer appropriate. Thus, it 
is common 
practice when assessing infants and young children to delay diagnosis of intellectual 
developmental 
disorder until 
after an appropriate course of intervention is provided. For older 
children and adults, the extent 
of support 
provided may allow for full 
participation in all 
activities of daily living and improved adaptive function. Diagnostic assessments must 
determine 
whether improved adaptive skills are the result 
of a stable, generalized new skill 
acquisition (in 
which case the diagnosis of intellectual 
developmental 
disorder may no longer be appropriate) or 
whether the improvement 
is contingent 
on the presence of supports and ongoing interventions (in 
which case the diagnosis of intellectual developmental disorder may still be appropriate). 


Risk and Prognostic Factors 



Genetic 
and 
physiological. 
Prenatal etiologies include genetic syndromes (e.g., sequence variations 
or copy number variants involving one or more genes; 
chromosomal 
disorders), inborn errors of 
metabolism, brain malformations, maternal 
disease (including placental 
disease), and 
environmental 
influences (e.g., alcohol, other drugs, toxins, teratogens). Perinatal 
causes include 
a variety of labor and delivery related events leading to neonatal 
encephalopathy. Postnatal 
causes include hypoxic ischemic injury, traumatic brain injury, infections, demyelinating 
disorders, seizure disorders (e.g., infantile spasms), severe and chronic social 
deprivation, and 
toxic metabolic syndromes and intoxications (e.g., lead, mercury). 


Culture-Related Diagnostic Issues 


Intellectual 
developmental 
disorder occurs across ethnoracial 
groups. Prevalence differences 
across social 
and cultural 
contexts may be due to variation in environmental 
risks (e.g., perinatal 
injury, chronic social 
deprivation) for the disorder that 
are associated with socioeconomic status 
and access to quality health care. For example, in Western Australia, the population prevalence 
of intellectual 
developmental 
disorder among Aboriginal 
children is 39 per 1,000 people, as 
opposed to 16 per 1,000 for the more affluent 
non-Aboriginal 
youth population. Cultural 
sensitivity and knowledge of sociostructural 
conditions are needed during assessment, and the 
individual s socioeconomic, ethnic, cultural, and linguistic background; 
available experiences; 
and adaptive functioning within his or her community and cultural 
setting must 
be considered. 
Cultural 
explanations for intellectual 
developmental 
disorder vary and may include cultural 
beliefs about 
supernatural 
influences and punishment 
for presumed or actual 
wrongdoing by the 
mother or parents, which can be associated with shame and underreporting of the disorder. 


Sex- and Gender-Related Diagnostic Issues 


Overall, males are more likely than females to be diagnosed with both mild (average male:female 
ratio 1.6:1) and severe (average male:female ratio 1.2:1) forms of intellectual 
developmental 
disorder. However, sex ratios vary widely in reported studies. Sex-linked genetic factors, sex 
differences in other genetic factors such as specific copy number variants, and male vulnerability 
to brain insult may account for some of the sex differences. 


Association With Suicidal 
Thoughts or Behavior 


Individuals with intellectual 
developmental 
disorder can be at 
risk for suicide associated with 
comorbid mental 
disorder, higher intellectual 
and adaptive function, and immediate past 
stressors. Comorbid mental 
disorder may manifest 
atypically in intellectual 
developmental 
disorder; 
thus, recognizing comorbidity and screening for suicidal 
thoughts is important 
in the 
assessment process, with particular attention to change in behavior of the individual. 


45 


Differential 
Diagnosis 


The diagnosis of intellectual 
developmental 
disorder should be made whenever Criteria A, B, 
and C 
are met. A diagnosis of intellectual 
developmental 
disorder should not 
be assumed 
because of a particular genetic or medical 
condition. A genetic syndrome linked to intellectual 
developmental 
disorder should be noted as a concurrent 
diagnosis with the intellectual 



developmental disorder. 
Major and 
mild 
neurocognitive 
disorders. 
Intellectual 
developmental 
disorder is categorized as a 
neurodevelopmental 
disorder and is distinct 
from 
the neurocognitive disorders, which are 
characterized by a loss of cognitive functioning. Major neurocognitive disorder may co-occur 
with intellectual 
developmental 
disorder (e.g., an individual 
with Down syndrome who develops 
Alzheimer s disease, or an individual 
with intellectual 
developmental 
disorder who loses further 
cognitive capacity following a head injury). In such cases, the diagnoses of intellectual 
developmental 
disorder and neurocognitive disorder may both be given. Moreover, when there is 
stabilization of cognitive functioning following traumatic or nontraumatic brain injury with onset 
in the developmental 
period (childhood and adolescence), and there is no continuing cognitive 
decline, both neurocognitive disorder and intellectual 
developmental 
disorder diagnoses can be 


used if diagnostic criteria are met for intellectual developmental disorder. 
Communication 
disorders 
and 
specific 
learning 
disorder. 
These neurodevelopmental 
disorders are 
specific to the communication and learning domains and do not 
show deficits in intellectual 
and 


adaptive behavior. They may co-occur with intellectual 
developmental 
disorder. Both diagnoses 
are made if full 
criteria are met 
for intellectual 
developmental 
disorder and a communication 
disorder or specific learning disorder. 


Autism spectrum disorder. 
Intellectual 
developmental 
disorder is common among individuals with 
autism 
spectrum 
disorder. Assessment 
of intellectual 
ability may be complicated by social-
communication and behavior deficits inherent 
to autism 
spectrum 
disorder, which may interfere 
with understanding and complying with test 
procedures. Appropriate assessment 
of intellectual 
functioning in autism 
spectrum 
disorder is essential, with reassessment 
across the developmental 
period, because IQ scores in autism 
spectrum 
disorder may be unstable, particularly in early 
childhood. 


Comorbidity 


Co-occurring neurodevelopmental 
and other mental 
and medical 
conditions are frequent 
in 
intellectual 
developmental 
disorder, with rates of some conditions (e.g., mental 
disorders, 
cerebral 
palsy, and epilepsy) three to four times higher than in the general 
population. The 
prognosis and outcome of co-occurring diagnoses may be influenced by the presence of 
intellectual 
developmental 
disorder. Assessment 
procedures may require modifications because 
of associated disorders, including communication disorders, autism 
spectrum 
disorder, and 
motor, sensory, or other disorders. Knowledgeable informants are essential 
for identifying 
symptoms such as irritability, mood dysregulation, aggression, eating problems, and sleep 
problems, and for assessing adaptive functioning in various community settings. 


The most 
common co-occurring neurodevelopmental 
and other mental 
disorders are 
attention-deficit/hyperactivity disorder; 
depressive and bipolar disorders; 
anxiety disorders; 
autism 
spectrum 
disorder; 
stereotypic movement 
disorder (with or without 
self-injurious 
behavior); 
impulse-control 
disorders; 
and major neurocognitive disorder. Major depressive 
disorder may occur throughout 
the range of severity of intellectual 
developmental 
disorder. Self-
injurious behavior requires prompt 
diagnostic attention and may warrant 
a separate diagnosis of 
stereotypic movement 
disorder. Individuals with intellectual 
developmental 
disorder, particularly 
those with more severe intellectual 
developmental 
disorder, may also exhibit 
aggression and 
disruptive behaviors, including harm of others or property destruction. 



46 


Individuals with intellectual 
developmental 
disorder disproportionately have more health 
problems, including obesity, than the general 
population. Frequently they cannot 
verbalize 
physical 
symptoms they are experiencing. This may lead to health problems being undiagnosed 
and untreated. 


Relationship to Other Classifications 


ICD-11 uses the term 
disorders of 
intellectual 
development 
to indicate that 
these are disorders 
that 
involve impaired brain functioning early in life. These disorders are described in ICD-11 as 
a metasyndrome occurring in the developmental 
period analogous to dementia or major 
neurocognitive disorder in later life. There are four subtypes of disorders of intellectual 
development in ICD-11: mild, moderate, severe, and profound. 


The American Association on Intellectual 
and Developmental 
Disabilities (AAIDD) uses the 
term 
intellectual 
disability. The AAIDD s classification is multidimensional 
rather than 
categorical 
and is based on the disability construct. Rather than listing severity specifiers as is 
done in DSM-5, the AAIDD emphasizes a profile of supports based on severity. 


Global 
Developmental 
Delay 


F88 


This diagnosis is reserved 
for individuals under 
the 
age 
of 
5 
years when 
the 
clinical 
severity level cannot 
be 
reliably assessed 
during 
early childhood. 
This category is 
diagnosed 
when 
an 
individual fails to 
meet 
expected 
developmental milestones in 
several areas of 
intellectual functioning, 
and 
applies to 
individuals who 
are 
unable 
to 
undergo 
systematic assessments of 
intellectual functioning, 
including 
children 
who 
are 
too 
young 
to 
participate 
in 
standardized 
testing. 
This category requires 
reassessment 
after a 
period 
of 
time. 


Unspecified 
Intellectual 
Developmental 
Disorder 
(Intellectual 
Disability) 


F79 


This category is reserved 
for individuals over 
the 
age 
of 
5 
years when 
assessment 
of 
the 
degree 
of 
intellectual developmental disorder (intellectual disability) by means of 
locally available 
procedures is rendered 
difficult 
or impossible 
because 
of 
associated 
sensory or physical impairments, 
as in 
blindness or prelingual deafness; 
locomotor 
disability; 
or presence 
of 
severe 
problem behaviors or co-occurring 
mental disorder. 
This category should 
only be 
used 
in 
exceptional circumstances and 
requires 
reassessment 
after a 
period 
of 
time. 



Communication Disorders 


Disorders of communication include deficits in language, speech, and communication. Speech 
is 
the expressive production of sounds and includes an individual s articulation, fluency, voice, and 
resonance quality. Language 
includes the form, function, and use of a conventional 
system 
of 
symbols (i.e., spoken words, sign language, written words, pictures) in a 


47 


rule-governed manner for communication. Communication 
includes any verbal 
or nonverbal 
behavior (whether intentional 
or unintentional) that 
has the potential 
to influence the behavior, 
ideas, or attitudes of another individual. Assessments of speech, language, and communication 
abilities must 
take into account 
the individual's cultural 
and language context, particularly for 
individuals growing up in bilingual 
environments. The standardized measures of language 
development 
and of nonverbal 
intellectual 
capacity must 
be relevant 
for the cultural 
and 
linguistic group (i.e., tests developed and standardized for one group may not 
provide 
appropriate norms for a different 
group). The diagnostic category of communication disorders 
includes the following: 
language disorder, speech sound disorder, childhood-onset 
fluency 
disorder (stuttering), social (pragmatic) communication disorder, and unspecified communication 
disorders Sex differences in the development 
of early communication may give rise to higher 
prevalence rates of communication disorders in boys compared with girls. Given the associated 
features of communication disorders and the relationship of communication to other 
developmental 
domains, communication disorders have high rates of comorbidity with other 
neurodevelopmental 
disorders (e.g., autism 
spectrum 
disorder, attention-deficit/hyperactivity 
disorder (ADHD), specific learning disorder, intellectual 
developmental 
disorder [intellectual 
disability]), mental 
disorders (e.g., anxiety disorders), and some medical 
conditions (e.g., seizure 
disorders, specific chromosome abnormalities). 


Language Disorder 


Diagnostic Criteria 
F80.2 


A. 
Persistent 
difficulties in 
the 
acquisition 
and 
use 
of 
language 
across modalities 
(i.e., 
spoken, 
written, 
sign 
language, 
or other) due 
to 
deficits in 
comprehension 
or production 
that 
include 
the 
following: 
1. 
Reduced 
vocabulary (word 
knowledge 
and 
use). 
2. 
Limited 
sentence 
structure 
(ability to 
put 
words and 
word 
endings together to 
form sentences based 
on 
the 
rules of 
grammar and 
morphology). 
3. 
Impairments in 
discourse 
(ability to 
use 
vocabulary and 
connect 
sentences to 
explain 
or describe 
a 
topic or series of 
events or have 
a 
conversation). 

B. 
Language 
abilities are 
substantially and 
quantifiably below those 
expected 
for 
age, 
resulting 
in 
functional limitations in 
effective 
communication, 
social 
participation, 
academic achievement, 
or occupational performance, 
individually 
or in 
any combination. 
C. 
Onset 
of 
symptoms is in 
the 
early developmental period. 
D. 
The 
difficulties are 
not 
attributable 
to 
hearing 
or other sensory impairment, 
motor 
dysfunction, 
or another medical or neurological condition 
and 
are 
not 
better 
explained 
by intellectual developmental disorder (intellectual disability) or global 
developmental delay. 
Diagnostic Features 


The essential 
features of language disorder are difficulties in the acquisition and use of language 
due to deficits in the comprehension or production of vocabulary, grammar, sentence structure, 
and discourse. The language deficits are evident 
in spoken communication, written 
communication, or sign language. Language learning and use is dependent 
on both receptive and 
expressive skills. Expressive ability 
refers to the production of vocal, gestural, or verbal 
signals, 
while receptive ability 
refers to the process of receiving and comprehending language messages. 
Language skills need to be assessed in both expressive and receptive modalities as these may 
differ in severity. 


Language disorder usually affects vocabulary and grammar, and these effects then limit 
the 
capacity for discourse. The child s first words and phrases are likely to be delayed 


48 


in onset; 
vocabulary size is smaller and less varied than expected; 
and sentences are shorter 
and less complex with grammatical 
errors, especially in past 
tense. Deficits in comprehension of 
language are frequently underestimated, as children may be good at 
using context 
to infer 
meaning. There may be word-finding problems, impoverished verbal 
definitions, or poor 
understanding of synonyms, multiple meanings, or word play appropriate for age and culture. 
Problems with remembering new words and sentences are manifested by difficulties following 
instructions of increasing length, difficulties rehearsing strings of verbal 
information (e.g., 
remembering a phone number or a shopping list), and difficulties remembering novel 
sound 
sequences, a skill 
that 
may be important 
for learning new words. Difficulties with discourse are 
shown by a reduced ability to provide adequate information about 
the key events and to narrate a 
coherent story. 


The language difficulty is manifest 
by abilities substantially and quantifiably below that 
expected for age and significantly interfering with academic achievement, occupational 
performance, effective communication, or socialization (Criterion B). A diagnosis of language 
disorder is made based on the synthesis of the individual s history, direct 
clinical 
observation in 
different 
contexts (i.e., home, school, or work), and scores from 
standardized tests of language 
ability that can be used to guide estimates of severity. 


Associated Features 



Individuals, even children, can be adept 
at 
accommodating to their limited language. They may 
appear to be shy or reticent 
to talk. Affected individuals may prefer to communicate only with 
family members or other familiar individuals. Although these social 
indicators are not 
diagnostic 
of a language disorder, if they are notable and persistent, they warrant 
referral 
for a full 
language 
assessment. 


Development and Course 


Language acquisition is marked by changes from 
onset 
in toddlerhood to the adult 
level 
of 
competency that 
appears during adolescence. Changes appear across the dimensions of language 
(sounds, words, grammar, narratives/expository texts, and conversational 
skills) in age-graded 
increments and synchronies. Language disorder emerges during the early developmental 
period; 
however, there is considerable variation in early vocabulary acquisition and early word 
combinations. Individual 
differences in early childhood are not, as single indicators, highly 
predictive of later outcomes, although a late onset 
of language at 
age 24 months in a population-
based sample was the best 
predictor of outcomes at 
age 7 years. By age 4 years, individual 
differences in language ability are more stable, with better measurement 
accuracy, and are highly 
predictive of later outcomes. Language disorder diagnosed in children age 4 years and older is 
likely to be stable over time and typically persists into adulthood, although the particular profile 
of language strengths and deficits is likely to change over the course of development. 


Language disorders can have social consequences across the lifespan. Children with language 
disorders are at 
risk for peer victimization. For females with childhood language disorders, there 
could be almost 
three times the risk compared with unaffected children for sexual 
assault 
in 
adulthood. 


Risk and Prognostic Factors 


Children with receptive language impairments have a poorer prognosis than those with 
predominantly expressive impairments. Receptive language impairments are more resistant 
to 
treatment, and difficulties with reading comprehension are frequently seen. 


Environmental. 
Bilingualism 
does not 
cause or worsen a language disorder, but children who are 
bilingual may demonstrate delays or differences in language development. A 


49 


language disorder in bilingual 
children will 
affect 
both languages; 
therefore, assessment 
across 


both languages is important to consider. 
Genetic 
and 
physiological. 
Language disorders are highly heritable, and family members are more 
likely to have a history of language impairment. Population-based twin studies consistently 
report 
substantial 
heritability for language disorder, and molecular studies suggest 
multiple genes 
interacting on causal pathways. 


Differential 
Diagnosis 


Normal 
variations 
in 
language. 
Language disorder needs to be distinguished from 
normal 
developmental 
variations, and this distinction may be difficult 
to make before age 4 years. 
Regional, social, or cultural/ethnic variations of language (e.g., dialects) must 
be considered 



when an individual is being assessed for language impairment. 
Hearing 
or other sensory 
impairment. 
Hearing impairment 
needs to be excluded as the primary 
cause of language difficulties. Language deficits may be associated with a hearing impairment, 
other sensory deficit, or a speech-motor deficit. When language deficits are in excess of those 


usually associated with these problems, a diagnosis of language disorder may be made. 
Intellectual 
developmental 
disorder (intellectual 
disability). 
Language impairment 
is often the 
presenting feature of intellectual 
developmental 
disorder. However, the definitive diagnosis of 


intellectual 
developmental 
disorder may not 
be made until 
the child is able to complete 
standardized assessments. Language disorder can occur with varying degrees of intellectual 
ability, and a discrepancy between verbal 
and nonverbal 
ability is not 
necessary for a diagnosis 
of language disorder. 


Autism spectrum disorder. 
Autism 
spectrum 
disorder frequently manifests with delayed language 
development. However, autism 
spectrum 
disorder is often accompanied by behaviors not 
present 
in language disorder, such as lack of social 
interest 
or unusual 
social 
interactions (e.g., pulling 
individuals by the hand without 
any attempt 
to look at 
them), odd play patterns (e.g., carrying 
toys around but 
never playing with them), unusual 
communication patterns (e.g., knowing the 
alphabet 
but 
not 
responding to own name), and rigid adherence to routines and repetitive 
behaviors (e.g., flapping, spinning, echolalia). 


Neurological 
disorders. 
Language disorder can be acquired in association with neurological 


disorders, including epilepsy (e.g., acquired aphasia or Landau-Kleffner syndrome). 
Language 
regression. 
Loss of speech and language in a child at 
any age warrants thorough 
assessment 
to determine if there is a specific neurological 
condition, such as Landau-Kleffner 
syndrome. Language loss may be a symptom 
of seizures, and a diagnostic assessment 
is 
necessary to exclude the presence of epilepsy (e.g., routine and sleep electroencephalogram). 
Declines in critical 
social 
and communication behaviors during the first 
2 years of life are 
evident 
in most 
children presenting with autism 
spectrum 
disorder and should signal 
the need for 
autism spectrum disorder assessment. 


Comorbidity 


Language disorder may be associated with other neurodevelopmental 
disorders in terms of 
specific learning disorder (literacy and numeracy), intellectual 
developmental 
disorder, attentiondeficit/
hyperactivity disorder, autism 
spectrum 
disorder, and developmental 
coordination 
disorder. It 
is also associated with social 
(pragmatic) communication disorder. In clinical 
samples, language disorder may co-occur with speech sound disorder, although data from 
a large 
population-based sample of 6-year-old children in the United States suggest 
comorbidity might 
be rare (1.3%). A positive family history of speech or language disorders is often present. 


50 


Speech 
Sound 
Disorder 


F80.0Diagnostic Criteria

A. 
Persistent 
difficulty with 
speech 
sound 
production 
that 
interferes with 
speech 
intelligibility or prevents verbal communication 
of 
messages. 
B. 
The 
disturbance 
causes limitations in 
effective 
communication 
that 
interfere 
with 
social participation, 
academic achievement, 
or occupational performance, 
individually or in 
any combination. 
C. 
Onset 
of 
symptoms is in 
the 
early developmental period. 
D. 
The 
difficulties are 
not 
attributable 
to 
congenital or acquired 
conditions, 
such 
as 
cerebral palsy, 
cleft 
palate, 
deafness or hearing 
loss, 
traumatic brain 
injury, 
or 
other medical or neurological conditions. 
Diagnostic Features 


Speech sound production describes the clear articulation of the phonemes (i.e., individual 
sounds) that 
in combination make up spoken words. Speech sound production requires both the 
phonological 
knowledge of speech sounds and the ability to coordinate the movements of the 
articulators (i.e., the jaw, tongue, and lips,) with breathing and vocalizing for speech. Children 
with speech production difficulties may experience difficulty with phonological 
knowledge of 
speech sounds or the ability to coordinate movements for speech in varying degrees. A speech 
sound disorder is diagnosed when speech sound production is not 
what 
would be expected based 
on the child s age and developmental 
stage and when the deficits are not 
the result 
of a physical, 
structural, neurological, or hearing impairment. Among typically developing children at 
age 3 
years, overall 
speech should be intelligible, whereas at 
age 2 years, only 50% may be 
understandable. Boys are more likely (range of 1.5 1.8 to 1.0) to have a speech sound disorder 
than girls. 


Associated Features 


Language disorder may be found to co-occur with speech sound disorder, although co-
occurrences are rare by age 6 years. A positive family history of speech or language disorders is 
often present. 


If the ability to rapidly coordinate the articulators is a particular aspect 
of difficulty, there 
may be a history of delay or incoordination in acquiring skills that also utilize the articulators and 
related facial 
musculature; 
among others, these skills include chewing, maintaining mouth 
closure, and blowing the nose. Other areas of motor coordination may be impaired as in 
developmental 
coordination disorder. The terms childhood apraxia of 
speech 
and verbal 
dyspraxia are used for speech production problems with motor components. 


Development and Course 


Learning to produce speech sounds clearly and accurately and learning to produce connected 
speech fluently are developmental 
skills. Articulation of speech sounds follows a developmental 
pattern, which is reflected in the age norms of standardized tests. It 
is not 
unusual 
for typically 
developing children to use developmental 
processes for shortening words and syllables as they 
are learning to talk, but 
their progression in mastering speech sound production should result 
in 
mostly intelligible speech by age 3 years. Children with speech sound disorder continue to use 



immature phonological 
simplification processes past 
the age when most 
children can produce 
words clearly. 


Most 
speech sounds should be produced clearly and most 
words should be pronounced 
accurately according to age and community norms by age 5 years. The most 


51 


frequently misarticulated sounds in English also tend to be learned later, leading them 
to be 
called the  late eight  (l, 
r, 
s, 
z, 
th, 
ch, 
dzh, 
and zh). Misarticulation of any of these sounds by 
itself could be considered within normal 
limits up to age 8 years; 
however, when multiple sounds 
are involved, it 
is important 
to target 
some of those sounds as part 
of a plan to improve 
intelligibility, rather than waiting until 
the age at 
which almost 
all 
children can produce them 
accurately. Lisping (i.e., misarticulating sibilants) is particularly common and may involve 
frontal 
or lateral 
patterns of airstream 
direction. It 
may be associated with a tongue-thrust 
swallowing pattern. 


Most 
children with speech sound disorder respond well 
to treatment, and speech difficulties 
improve over time, and thus the disorder may not 
be lifelong. However, when a language 
disorder is also present, the speech disorder has a poorer prognosis and may be associated with 
specific learning disorder. 


Differential 
Diagnosis 


Normal 
variations 
in 
speech. 
Regional, social, or cultural/ethnic variations of speech should be 
considered before making the diagnosis. Bilingual 
children may demonstrate an overall 
lower 
intelligibility rating, make more overall 
consonant 
and vowel 
errors, and produce more 
uncommon error patterns than monolingual 
English-speaking children when assessed only in 
English. 


Hearing 
or other sensory 
impairment. 
Those who are deaf or hard of hearing may have speech 
sound production errors. When speech deficits are in excess of those usually associated with 
these problems, a diagnosis of speech sound disorder may be made. 


Structural 
deficits. 
Speech impairment may be due to structural deficits (e.g., cleft palate). 
Dysarthria. 
Speech impairment 
may be attributable to a motor disorder, such as cerebral 
palsy. 
Neurological 
signs, as well 
as distinctive features of voice, differentiate dysarthria from 
speech 
sound disorder, although in young children (under 3 years) differentiation may be difficult, 


particularly when there is no or minimal 
general 
body motor involvement 
(as in, e.g., Worster-
Drought syndrome). 
Selective 
mutism. 
Limited use of speech may be a sign of selective mutism, an anxiety disorder 


that 
is characterized by a lack of speech in one or more contexts or settings. Selective mutism 
may develop in children with a speech disorder because of embarrassment 
about 
their 
impairments, but 
many children with selective mutism 
exhibit 
normal 
speech in  safe  settings, 
such as at home or with close friends. 


Comorbidity 


Speech may be differentially impaired in certain genetic conditions (e.g., Down syndrome, 22q 
deletion, FoxP2 gene mutation). If present, these should also be coded. 



Childhood-Onset Fluency Disorder (Stuttering) 


Diagnostic Criteria 
F80.81 


A. 
Disturbances in 
the 
normal fluency and 
time 
patterning 
of 
speech 
that 
are 
inappropriate 
for the 
individual s age 
and 
language 
skills, 
persist 
over time, 
and 
are 
characterized 
by frequent 
and 
marked 
occurrences of 
one 
(or more) of 
the 
following: 
1. 
Sound 
and 
syllable 
repetitions. 
2. 
Sound 
prolongations of 
consonants as well as vowels. 
52 


3. 
Broken 
words (e.g., 
pauses within 
a 
word). 
4. 
Audible 
or silent 
blocking 
(filled 
or unfilled 
pauses in 
speech). 
5. 
Circumlocutions (word 
substitutions to 
avoid 
problematic words). 
6. 
Words produced 
with 
an 
excess of 
physical tension. 
7. 
Monosyllabic whole-word 
repetitions (e.g., 
 I-I-I-I 
see 
him ). 
B. 
The 
disturbance 
causes anxiety about 
speaking 
or limitations in 
effective 
communication, 
social participation, 
or academic or occupational performance, 
individually or in 
any combination. 
C. 
The 
onset 
of 
symptoms is in 
the 
early developmental period. 
(Note: 
Later-onset 
cases are 
diagnosed 
as F98.5 
adult-onset 
fluency disorder.) 
D. 
The 
disturbance 
is not 
attributable 
to 
a 
speech-motor or sensory deficit, 
dysfluency associated 
with 
neurological insult 
(e.g., 
stroke, 
tumor, 
trauma), 
or 
another medical condition 
and 
is not 
better explained 
by another mental 
disorder. 
Diagnostic Features 


The essential 
feature of childhood-onset 
fluency disorder (stuttering) is a disturbance in the 
normal 
fluency and time patterning of speech that 
is inappropriate for the individual s age. This 
disturbance is characterized by frequent 
repetitions or prolongations of sounds or syllables and 
by other types of speech dysfluencies, including broken words (e.g., pauses within a word), 
audible or silent 
blocking (i.e., filled or unfilled pauses in speech), circumlocutions (i.e., word 
substitutions to avoid problematic words), words produced with an excess of physical 
tension, 
and monosyllabic whole-word repetitions (e.g.,  I-I-I-I see him ). The disturbance in fluency 
may interfere with academic or occupational 
achievement 
and with social 
communication. The 
extent 
of the disturbance varies from 
situation to situation and often is more severe when there is 
special 
pressure to communicate (e.g., giving a report 
at 
school, interviewing for a job). 
Dysfluency is often absent during oral reading, singing, or talking to inanimate objects or to pets. 



Associated Features 


Fearful 
anticipation of the problem 
may develop. The speaker may attempt 
to avoid dysfluencies 
by linguistic mechanisms (e.g., altering the rate of speech, avoiding certain words or sounds) or 
by avoiding certain speech situations, such as telephoning or public speaking. In addition to 
being features of the condition, stress and anxiety have been shown to exacerbate dysfluency. 


Childhood-onset 
fluency disorder may also be accompanied by motor movements (e.g., eye 
blinks, tics, tremors of the lips or face, jerking of the head, breathing movements, fist 
clenching). 
Children with fluency disorder show a range of language abilities, and the relationship between 
fluency disorder and language abilities is unclear. 


Studies have shown both structural 
and functional 
neurological 
differences in children who 
stutter. Males are more likely to stutter than females, with estimates varying depending on the 
age and possible cause of stuttering. Causes of stuttering are multifactorial, including certain 
genetic and neurophysiological factors. 


Development and Course 


Childhood-onset 
fluency disorder, or developmental 
stuttering, occurs by age 6 for 80% 90% of 
affected individuals, with age at 
onset 
ranging from 
2 to 7 years. The onset 
can be insidious or 
more sudden. Typically, dysfluencies start 
gradually, with repetition of initial 
consonants, first 
words of a phrase, or long words. The child may not 
be aware of dysfluencies. As the disorder 
progresses, the dysfluencies become more frequent 
and interfering, occurring on the most 
meaningful 
words or phrases in the utterance. As the child becomes aware of the speech 
difficulty, he or she may develop mechanisms for avoiding the 


53 


dysfluencies and emotional 
responses, including avoidance of public speaking and use of short 
and simple utterances. Longitudinal 
research shows that 
65% 85% of children recover from 
the 
dysfluency, with severity of fluency disorder at 
age 8 years predicting recovery or persistence 
into adolescence and beyond. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
The risk of stuttering among first-degree biological 
relatives of 
individuals with childhood-onset 
fluency disorder is more than three times the risk in the general 
population. To date, mutations of four genes that 
underlie some cases of stuttering have been 
identified. 


Functional 
Consequences of Childhood-Onset Fluency Disorder 
(Stuttering) 


In addition to being features of the condition, stress and anxiety can exacerbate dysfluency. 
Impairment 
of social 
functioning may result 
from 
this anxiety. Negative communication attitudes 
may be a functional 
consequence of stuttering starting in the preschool 
years and increasing with 
age. 


Differential 
Diagnosis 



Sensory 
deficits. 
Dysfluencies of speech may be associated with a hearing impairment 
or other 
sensory deficit 
or a speech-motor deficit. When the speech dysfluencies are in excess of those 
usually associated with these problems, a diagnosis of childhood-onset 
fluency disorder may be 
made. 


Normal 
speech 
dysfluencies. 
The disorder must 
be distinguished from 
normal 
dysfluencies that 
occur frequently in young children, which include whole-word or phrase repetitions (e.g.,  I 
want, I want 
ice cream ), incomplete phrases, interjections, unfilled pauses, and parenthetical 
remarks. If these difficulties increase in frequency or complexity as the child grows older, a 
diagnosis of childhood-onset fluency disorder may be appropriate. 
Specific 
learning 
disorder, 
with 
impairment 
in 
reading. 
Children who have dysfluencies when they 


read aloud may be diagnosed mistakenly as having a reading disorder. Oral 
reading fluency 
typically is measured by timed assessments. Slower reading rates may not 
accurately reflect 
the 
actual reading ability of children who stutter. 


Bilingualism. 
It 
is necessary to distinguish between dysfluencies resulting from 
attempts to learn 
a new language and dysfluencies that 
indicate a fluency disorder, which typically appear in both 
languages. 


Medication 
side 
effects. 
Stuttering may occur as a side effect 
of medication and may be detected 


by a temporal relationship with exposure to the medication. 
Adult-onset 
dysfluencies. 
If onset 
of dysfluencies is during or after adolescence, it 
is an  adultonset 
dysfluency  rather than a neurodevelopmental 
disorder. Adult-onset 
dysfluencies are 
associated with specific neurological 
insults and a variety of medical 
conditions and mental 
disorders and may be specified with them, but they are not a DSM-5 diagnosis. 


Tourette s 
disorder. 
Vocal 
tics and repetitive vocalizations of Tourette s disorder should be 
distinguishable from 
the repetitive sounds of childhood-onset 
fluency disorder by their nature 
and timing. 


Comorbidity 


Childhood-onset 
fluency disorder can co-occur with other disorders, such as attentiondeficit/
hyperactivity disorder, autism spectrum disorder, intellectual developmental 


54 


disorder (intellectual 
disability), language disorder or specific learning disorder, seizure 
disorders, social anxiety disorder, speech sound disorder, and other developmental disorders. 


Social 
(Pragmatic) Communication 
Disorder 


Diagnostic Criteria 
F80.82 
A. 
Persistent 
difficulties in 
the 
social use 
of 
verbal and 
nonverbal communication 
as 
manifested 
by all of 
the 
following: 



1. 
Deficits in 
using 
communication 
for social purposes, 
such 
as greeting 
and 
sharing 
information, 
in 
a 
manner that 
is appropriate 
for the 
social context. 
2. 
Impairment 
of 
the 
ability to 
change 
communication 
to 
match 
context 
or the 
needs of 
the 
listener, 
such 
as speaking 
differently in 
a 
classroom than 
on 
a 
playground, 
talking 
differently to 
a 
child 
than 
to 
an 
adult, 
and 
avoiding 
use 
of 
overly formal language. 
3. 
Difficulties following 
rules for conversation 
and 
storytelling, 
such 
as taking 
turns in 
conversation, 
rephrasing 
when 
misunderstood, 
and 
knowing 
how to 
use 
verbal and 
nonverbal signals to 
regulate 
interaction. 
4. 
Difficulties understanding 
what 
is not 
explicitly stated 
(e.g., 
making 
inferences) and 
nonliteral or ambiguous meanings of 
language 
(e.g., 
idioms, 
humor, 
metaphors, 
multiple 
meanings that 
depend 
on 
the 
context 
for 
interpretation). 
B. 
The 
deficits result 
in 
functional limitations in 
effective 
communication, 
social 
participation, 
social relationships, 
academic achievement, 
or occupational 
performance, 
individually or in 
combination. 
C. 
The 
onset 
of 
the 
symptoms is in 
the 
early developmental period 
(but 
deficits may 
not 
become 
fully manifest 
until social communication 
demands exceed 
limited 
capacities). 
D. 
The 
symptoms are 
not 
attributable 
to 
another medical or neurological condition 
or to 
low abilities in 
the 
domains of 
word 
structure 
and 
grammar, 
and 
are 
not 
better explained 
by autism spectrum disorder, 
intellectual developmental 
disorder (intellectual disability), 
global developmental delay, 
or another mental 
disorder. 
Diagnostic Features 


Social 
(pragmatic) communication disorder is characterized by a primary difficulty with 
pragmatics 
(i.e., the social 
use of language and communication), as manifested by deficits in 
understanding and following social 
rules of both verbal 
and nonverbal 
communication in 
naturalistic contexts, changing language according to the needs of the listener or situation, and 
following rules for conversations and storytelling. The deficits in social 
communication result 
in 
functional 
limitations in effective communication, social 
participation, development 
of social 
relationships, academic achievement, or occupational 
performance. The deficits are not 
better 
explained by low abilities in the domains of structural 
language or cognitive ability or by autism 
spectrum disorder. 


Associated Features 


The most 
common associated feature of social 
(pragmatic) communication disorder is language 
impairment, which is characterized by a history of delay in reaching language milestones, and 
historical, if not 
current, structural 
language problems (see  Language Disorder  earlier in this 
chapter). Individuals with social communication deficits may 



55 


avoid social 
interactions. Attention-deficit/hyperactivity disorder (ADHD), emotional 
and 
behavioral 
problems, and specific learning disorders are also more common among affected 
individuals. 


Development and Course 


Because social 
(pragmatic) communication depends on adequate developmental 
progress in 
speech and language, diagnosis of social 
(pragmatic) communication disorder is rare among 
children younger than 4 years. By age 4 or 5 years, most 
children should possess adequate 
speech and language abilities to permit 
identification of specific deficits in social 
communication. Milder forms of the disorder may not 
become apparent 
until 
early adolescence, 
when language and social interactions become more complex. 


The outcome of social 
(pragmatic) communication disorder is variable, with some children 
improving substantially over time and others continuing to have difficulties persisting into 
adulthood. Even among those who have significant 
improvements, the early deficits in 
pragmatics may cause lasting impairments in social 
relationships and behavior and also low 
performance of other related skills, such as written expression, reading comprehension, and oral 
reading. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
A family history of autism 
spectrum 
disorder, communication 
disorders, or specific learning disorder appears to increase the risk for social 
(pragmatic) 
communication disorder; 
this includes siblings of children with these disorders who may present 
with early symptoms of social (pragmatic) communication disorder. 


Differential 
Diagnosis 


Autism spectrum disorder. 
Autism 
spectrum 
disorder is the primary diagnostic consideration for 
individuals presenting with social 
communication deficits. The two disorders can be 
differentiated by the presence in autism 
spectrum 
disorder of restricted/repetitive patterns of 
behavior, interests, or activities and their absence in social 
(pragmatic) communication disorder. 
Individuals with autism 
spectrum 
disorder may only display the restricted/repetitive patterns of 
behavior, interests, and activities during the early developmental 
period, so a comprehensive 
history should be obtained. Current 
absence of symptoms would not 
preclude a diagnosis of 
autism 
spectrum 
disorder, if the restricted interests and repetitive behaviors were present 
in the 
past. A diagnosis of social 
(pragmatic) communication disorder should be considered only if the 
current 
symptoms or developmental 
history fails to reveal 
evidence of symptoms that 
meet 
the 
diagnostic criteria for restricted/repetitive patterns of behavior, interests, or activities of autism 
spectrum 
disorder (i.e., Criterion B) causing current 
impairment. The social 
communication 
symptoms may be milder in social 
(pragmatic) communication disorder than in autism 
spectrum 
disorder, although qualitatively similar. 


Attention-deficit/hyperactivity 
disorder. 
Primary deficits of ADHD may cause impairments in social 
communication and functional 
limitations of effective communication, social 
participation, or 
academic achievement. 



Social 
anxiety 
disorder. 
The symptoms of social 
(pragmatic) communication disorder overlap with 
those of social 
anxiety disorder. The differentiating feature is the timing of the onset 
of 
symptoms. In social 
(pragmatic) communication disorder, the individual 
has never had effective 
social 
communication; 
in social 
anxiety disorder, the social 
communication skills developed 
appropriately but are not utilized because of anxiety, fear, or distress about social interactions. 


56 


Intellectual 
developmental 
disorder (intellectual 
disability) 
and 
global 
developmental 
delay. 


Social 
communication skills may be deficient 
among individuals with global 
developmental 
delay or 
intellectual 
developmental 
disorder, but 
a separate diagnosis is not 
given unless the social 
communication deficits are clearly in excess of the intellectual limitations. 


Unspecified 
Communication 
Disorder 


F80.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
communication 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for communication 
disorder or for any of 
the 
disorders in 
the 
neurodevelopmental disorders diagnostic class. 
The 
unspecified 
communication 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify 
the 
reason 
that 
the 
criteria 
are 
not 
met 
for communication 
disorder or for a 
specific 
neurodevelopmental disorder, 
and 
includes presentations in 
which 
there 
is 
insufficient 
information 
to 
make 
a 
more 
specific diagnosis. 


Autism Spectrum Disorder 


Autism Spectrum Disorder 


Diagnostic Criteria 
F84.0 


A. 
Persistent 
deficits in 
social communication 
and 
social interaction 
across multiple 
contexts, 
as manifested 
by all of 
the 
following, 
currently or by history (examples 
are 
illustrative, 
not 
exhaustive; 
see 
text): 
1. 
Deficits in 
social-emotional reciprocity, 
ranging, 
for example, 
from abnormal 
social approach 
and 
failure 
of 
normal back-and-forth 
conversation; 
to 
reduced 
sharing 
of 
interests, 
emotions, 
or affect; 
to 
failure 
to 
initiate 
or respond 
to 

social interactions. 


2. 
Deficits in 
nonverbal communicative 
behaviors used 
for social interaction, 
ranging, 
for example, 
from poorly integrated 
verbal and 
nonverbal 
communication; 
to 
abnormalities in 
eye 
contact 
and 
body language 
or deficits 
in 
understanding 
and 
use 
of 
gestures; 
to 
a 
total lack of 
facial expressions and 
nonverbal communication. 
3. 
Deficits in 
developing, 
maintaining, 
and 
understanding 
relationships, 
ranging, 
for example, 
from difficulties adjusting 
behavior to 
suit 
various social contexts; 
to 
difficulties in 
sharing 
imaginative 
play or in 
making 
friends; 
to 
absence 
of 
interest 
in 
peers. 
B. 
Restricted, 
repetitive 
patterns of 
behavior, 
interests, 
or activities, 
as manifested 
by at 
least 
two 
of 
the 
following, 
currently or by history (examples are 
illustrative, 
not 
exhaustive; 
see 
text): 
1. 
Stereotyped 
or repetitive 
motor movements, 
use 
of 
objects, 
or speech 
(e.g., 
simple 
motor stereotypies, 
lining 
up 
toys or flipping 
objects, 
echolalia, 
idiosyncratic phrases). 
57 


2. 
Insistence 
on 
sameness, 
inflexible 
adherence 
to 
routines, 
or ritualized 
patterns of 
verbal or nonverbal behavior (e.g., 
extreme 
distress at 
small 
changes, 
difficulties with 
transitions, 
rigid 
thinking 
patterns, 
greeting 
rituals, 
need 
to 
take 
same 
route 
or eat 
same 
food 
every day). 
3. 
Highly restricted, 
fixated 
interests that 
are 
abnormal in 
intensity or focus (e.g., 
strong 
attachment 
to 
or preoccupation 
with 
unusual objects, 
excessively 
circumscribed 
or perseverative 
interests). 
4. 
Hyper- or hyporeactivity to 
sensory input 
or unusual interest 
in 
sensory 
aspects of 
the 
environment 
(e.g., 
apparent 
indifference 
to 
pain/temperature, 
adverse 
response 
to 
specific sounds or textures, 
excessive 
smelling 
or 
touching 
of 
objects, 
visual fascination 
with 
lights or movement). 
C. 
Symptoms must 
be 
present 
in 
the 
early developmental period 
(but 
may not 
become 
fully manifest 
until social demands exceed 
limited 
capacities, 
or may be 
masked 
by learned 
strategies in 
later life). 
D. 
Symptoms cause 
clinically significant 
impairment 
in 
social, 
occupational, 
or other 
important 
areas of 
current 
functioning. 
E. 
These 
disturbances are 
not 
better explained 
by intellectual developmental 
disorder (intellectual disability) or global developmental delay. 
Intellectual 
developmental disorder and 
autism spectrum disorder frequently co-occur; 
to 
make 
comorbid 
diagnoses of 
autism spectrum disorder and 
intellectual 
developmental disorder, 
social communication 
should 
be 
below that 
expected 
for 
general developmental level. 
Note: 
Individuals with 
a 
well-established 
DSM-IV 
diagnosis of 
autistic disorder, 
Asperger s disorder, 
or pervasive 
developmental disorder not 
otherwise 
specified 



should 
be 
given 
the 
diagnosis of 
autism spectrum disorder. 
Individuals who 
have 
marked 
deficits in 
social communication, 
but 
whose 
symptoms do 
not 
otherwise 
meet 
criteria 
for autism spectrum disorder, 
should 
be 
evaluated 
for social 
(pragmatic) communication 
disorder. 


Specify 
current 
severity based 
on 
social communication 
impairments and 
restricted, 
repetitive 
patterns of 
behavior (see 
Table 
2): 


Requiring 
very 
substantial 
support 
Requiring 
substantial 
support 
Requiring 
support 


Specify 
if: 


With 
or without accompanying 
intellectual 
impairment 
With 
or without accompanying 
language 
impairment 


Specify 
if: 


Associated 
with 
a 
known 
genetic 
or other medical 
condition 
or 
environmental 
factor 
(Coding 
note: 
Use 
additional code 
to 
identify the 
associated 
genetic or other medical condition.) 


Associated 
with 
a 
neurodevelopmental, 
mental, 
or behavioral 
problem 


Specify 
if: 
With 
catatonia 
(refer to 
the 
criteria 
for catatonia 
associated 
with 
another mental 
disorder, 
p. 
135, 
for definition) (Coding 
note: 
Use 
additional code 
F06.1 
catatonia 
associated 
with 
autism spectrum disorder to 
indicate 
the 
presence 
of 
the 
comorbid 
catatonia.) 


58 


TABLE 
2 
Severity 
levels 
for autism spectrum disorder (examples 
of level 
of 
support needs) 


Severity 
level 
Social 
communication 
Restricted, 
repetitive 
behaviors 


Level 3 


 Requiring very substantial 
support  


Level 2 


 Requiring substantial 
support  


Severe deficits in verbal and nonverbal social 
communication skills cause severe impairments 
in functioning, very limited initiation of social 
interactions, and minimal response to social 
overtures from others. For example, a person 
with few words of intelligible speech who rarely 
initiates interaction and, when he or she does, 
makes unusual approaches to meet needs only 
and responds to only very direct social 
approaches. 


Marked deficits in verbal and nonverbal social 
communication skills; social impairments 
apparent even with supports in place; limited 
initiation of social interactions; and reduced or 
abnormal responses to social overtures from 
others. For example, a person who speaks 
simple sentences, whose interaction is limited to 
narrow special interests, and who has markedly 


Inflexibility of behavior, extreme difficulty 
coping with change, or other 
restricted/repetitive behaviors markedly 
interfere with functioning in all spheres. 
Great distress/difficulty changing focus or 
action. 


Inflexibility of behavior, difficulty coping 
with change, or other restricted/repetitive 
behaviors appear frequently enough to be 
obvious to the casual observer and 
interfere with functioning in a variety of 
contexts. Distress and/or difficulty 
changing focus or action. 



odd nonverbal communication. 


Level 1 
Without supports in place, deficits in social 
Inflexibility of behavior causes significant 
communication cause noticeable impairments. 
interference with functioning in one or 


 Requiring support  


Difficulty initiating social interactions, and clear 
more contexts. Difficulty switching 
examples of atypical or unsuccessful responses 
between activities. Problems of 
to social overtures of others. May appear to 
organization and planning hamper 
have decreased interest in social interactions. 
independence. 
For example, a person who is able to speak in 
full sentences and engages in communication 
but whose to-and-fro conversation with others 
fails, and whose attempts to make friends are 
odd and typically unsuccessful. 


Recording Procedures 


It 
may be helpful 
to note level 
of support 
needed for each of the two core psychopathological 
domains in Table 2 
(e.g.,  requiring very substantial 
support 
for deficits in social 
communication 
and requiring substantial 
support 
for restricted, repetitive behaviors ). Specification of  with 
accompanying intellectual impairment  or  without accompanying 


59 


intellectual 
impairment  should be recorded next. Language impairment 
specification should be 
recorded thereafter. If there is accompanying language impairment, the current 
level 
of verbal 
functioning should be recorded (e.g.,  with accompanying language impairment no intelligible 
speech  or  with accompanying language impairment phrase speech ). 


For autism 
spectrum 
disorder for which the specifiers  associated with a known genetic or 
other medical 
condition or environmental 
factor  or  associated with a neurodevelopmental, 
mental, or behavioral 
problem  are appropriate, record autism 
spectrum 
disorder associated with 
(name of condition, disorder, or factor) (e.g., autism 
spectrum 
disorder associated with tuberous 
sclerosis complex). These specifiers apply to presentations in which the listed condition or 
problem 
is potentially relevant 
to the clinical 
care of the individual 
and do not 
necessarily 
indicate that 
the condition or problem 
is causally related to the autism 
spectrum 
disorder. If the 
associated neurodevelopmental, mental, or behavioral 
problem 
meets criteria for a 
neurodevelopmental 
or other mental 
disorder, both autism 
spectrum 
disorder and the other 
disorder should be diagnosed. 


If catatonia is present, record separately  catatonia associated with autism 
spectrum 
disorder.  For more information, see criteria for catatonia associated with another mental 
disorder in the chapter  Schizophrenia Spectrum and Other Psychotic Disorders.  


Specifiers 


The severity specifiers (see Table 2) may be used to describe succinctly the current 
symptomatology (which might 
fall 
below level 
1), with the recognition that 
severity may vary by 
context 
and fluctuate over time. Severity of social 
communication difficulties and restricted, 
repetitive behaviors should be separately rated. The descriptive severity categories should not 
be 
used to determine eligibility for and provision of services. Indeed, individuals with relatively 
better skills overall 
may experience different 
or even greater psychosocial 
challenges. Thus, 
service needs can only be developed at 
an individual 
level 
and through discussion of personal 
priorities and targets. 



Regarding the specifier  with or without 
accompanying intellectual 
impairment,  
understanding the (often uneven) intellectual 
profile of a child or adult 
with autism 
spectrum 
disorder is necessary for interpreting diagnostic features. Separate estimates of verbal 
and 
nonverbal 
skill 
are necessary (e.g., using untimed nonverbal 
tests to assess potential 
strengths in 
individuals with limited language). 


To use the specifier  with or without 
accompanying language impairment,  the current 
level 
of verbal 
functioning should be assessed and described. Examples of the specific descriptions for 
 with accompanying language impairment  might 
include no intelligible speech (nonverbal), 
single words only, or phrase speech. Language level 
in individuals  without 
accompanying 
language impairment  might 
be further described as speaks in full 
sentences or has fluent 
speech. 
Since receptive language may lag behind expressive language development 
in autism 
spectrum 
disorder, receptive and expressive language skills should be considered separately. 


The specifier  associated with a known genetic or other medical 
condition or environmental 
factor  can be applied when an individual 
has a known genetic condition (e.g., Rett 
syndrome, 
fragile X syndrome, Down syndrome), a known medical 
condition (e.g., epilepsy), or a history of 
environmental 
exposure in utero to a known teratogen or infection (e.g., fetal 
valproate 
syndrome, fetal 
alcohol 
syndrome, fetal 
rubella). This specifier should not 
be viewed as 
synonymous with causation of autism 
spectrum 
disorder. A condition may be listed as being 
associated with autism 
spectrum 
disorder when it 
is thought 
to be potentially clinically relevant 
or inform 
care and not 
because the clinician is asserting a cause. Examples include autism 
spectrum 
disorder associated with a unique genomic copy number variant 
that 
could be clinically 
relevant 
even if the specific abnormality may not 
have directly caused nor have previously been 
linked to autism 
spectrum 
disorder, or Crohn s disease, which could exacerbate behavioral 
symptoms. 


60 


The specifier  associated with a neurodevelopmental, mental, or behavioral 
problem  can be 
applied to indicate problems (e.g., irritability, sleep problems, self-injurious behavior, or 
developmental 
regression) that 
contribute to the functional 
formulation or are a focus of 
treatment. Additional 
neurodevelopmental, mental, or behavioral 
disorders should also be noted 
as separate diagnoses (e.g., attention-deficit/hyperactivity disorder; 
developmental 
coordination 
disorder; 
disruptive behavior, impulse-control, and conduct 
disorders; 
anxiety, depressive, or 
bipolar disorders; tics or Tourette s disorder; feeding, elimination, or sleep disorders). 


Catatonia can occur as a comorbid condition with autism 
spectrum 
disorder. In addition to 
classic symptoms of posturing, negativism 
(opposition or no response to instructions or external 
stimuli), mutism, and stupor, an increase or worsening of stereotypy and self-injurious behavior 
may form part of the symptom complex of catatonia in the setting of autism spectrum disorder. 


Diagnostic Features 


The essential 
features of autism 
spectrum 
disorder are persistent 
impairment 
in reciprocal 
social 
communication and social 
interaction (Criterion A), and restricted, repetitive patterns of 
behavior, interests, or activities (Criterion B). These symptoms are present 
from 
early childhood 
and limit 
or impair everyday functioning (Criteria C 
and D). The stage at 
which functional 
impairment 
becomes obvious will 
vary according to characteristics of the individual 
and his or 



her environment. Core diagnostic features are evident 
in the developmental 
period, but 
intervention, compensation, and current 
supports may mask difficulties in at 
least 
some contexts. 
Manifestations of the disorder also vary greatly depending on the severity of the autistic 
condition, developmental 
level, chronological 
age, and possibly gender; 
hence, the term 
spectrum. 
Individuals without 
cognitive or language impairment 
may have more subtle 
manifestation of deficits (e.g., Criterion A, Criterion B) than individuals with accompanying 
intellectual 
or language impairments and may be making great 
efforts to mask these deficits. 
Criterion A deficits in social 
communication will 
be more subtle if an individual 
has better 
overall 
communication skills (e.g., is verbally fluent, does not 
have intellectual 
impairments). 
Similarly, Criterion B 
deficits (i.e., restricted patterns of behavior and interests) may be less 
obvious if the interests are closer to age-typical 
norms (e.g., Ancient 
Egypt 
or trains as compared 
to wiggling a string). Autism 
spectrum 
disorder encompasses disorders previously referred to as 
early infantile autism, childhood autism, Kanner s autism, high-functioning autism, atypical 
autism, pervasive developmental 
disorder not 
otherwise specified, childhood disintegrative 
disorder, and Asperger s disorder. 


The impairments in social 
communication and social 
interaction specified in Criterion A are 
pervasive and sustained. Diagnoses are most 
valid and reliable when based on multiple sources 
of information, including clinician s observations, caregiver history, and, when possible, self-
report. Verbal 
and nonverbal 
deficits in social 
communication have varying manifestations, 
depending on the individual s age, intellectual 
level, and language ability, as well 
as other factors 
such as treatment 
history and current 
support. Many individuals have language deficits, ranging 
from 
complete lack of speech through language delays, poor comprehension of speech, echoed 
speech, or stilted and overly literal 
language. Even when formal 
language skills (e.g., 
vocabulary, grammar) are intact, the use of language for reciprocal 
social 
communication is 
impaired in autism spectrum disorder. 


Deficits in social-emotional 
reciprocity (i.e., the ability to engage with others and share 
thoughts and feelings) may be shown, for example, in young children with little or no initiation 
of social 
interaction and no sharing of emotions, along with reduced or absent 
imitation of 
others  behavior. What 
language exists is often one-sided, lacking in social 
reciprocity, and used 
to request 
or label 
rather than to comment, share feelings, or converse. In older children and 
adults without intellectual impairments or language delays, deficits in 


61 


social-emotional 
reciprocity may be most 
apparent 
in difficulties processing and responding 
to complex social 
cues (e.g., when and how to join a conversation, what 
not 
to say). Individuals 
who have developed compensation strategies for some social 
challenges still 
struggle in novel 
or 
unsupported situations and suffer from 
the effort 
and anxiety of consciously calculating what 
is 
socially intuitive for most 
individuals. This behavior may contribute to lower ascertainment 
of 
autism 
spectrum 
disorder in these individuals, perhaps especially in adult 
women. Thus, longer 
assessments, observation in naturalistic settings, and inquiring about 
any tolls of social 
interaction may be needed. If asked about 
the costs of social 
interaction, for example, these 
individuals might 
respond that 
social 
interactions are exhausting for them, that 
they are unable to 
concentrate because of the mental 
effort 
in monitoring social 
conventions, that 
their self-esteem 
is adversely affected by being unable to be themselves, and so forth. 



Deficits in nonverbal 
communicative behaviors used for social 
interaction are manifested by 
absent, reduced, or atypical 
use of eye contact 
(relative to cultural 
norms), gestures, facial 
expressions, body orientation, or speech intonation. An early feature of autism 
spectrum 
disorder 
is impaired joint 
attention as manifested by a lack of pointing, showing, or bringing objects to 
share interest 
with others, or failure to follow someone s pointing or eye gaze. Individuals may 
learn a few functional 
gestures, but 
their repertoire is smaller than that 
of others, and they often 
fail 
to use expressive gestures spontaneously in communication. Among young people and adults 
with fluent 
language, the difficulty in coordinating nonverbal 
communication with speech may 
give the impression of odd, wooden, or exaggerated  body language  during interactions. 
Impairment 
may be relatively subtle within individual 
modes (e.g., someone may have relatively 
good eye contact 
when speaking) but 
noticeable in poor integration of eye contact, gesture, body 
posture, prosody, and facial 
expression for social 
communication, or in difficulty maintaining 
these for sustained periods or when under stress. 


Deficits in developing, maintaining, and understanding relationships should be judged 
against 
norms for age, gender, and culture. There may be absent, reduced, or atypical 
social 
interest, manifested by rejection of others, passivity, or inappropriate approaches that 
seem 
aggressive or disruptive. These difficulties are particularly evident 
in young children, in whom 
there is often a lack of shared social 
play and imagination (e.g., age-appropriate flexible pretend 
play) and, later, insistence on playing by very fixed rules. Older individuals may struggle to 
understand what 
behavior is considered appropriate in one situation but 
not 
another (e.g., casual 
behavior during a job interview), or the different 
ways that 
language may be used to 
communicate (e.g., irony, white lies). There may be an apparent 
preference for solitary activities 
or for interacting with much younger or older people. Frequently, there is a desire to establish 
friendships without 
a complete or realistic idea of what 
friendship entails (e.g., one-sided 
friendships or friendships based solely on shared special 
interests). Relationships with siblings, 
coworkers, and caregivers are also important to consider (in terms of reciprocity). 


Autism 
spectrum 
disorder is also defined by restricted, repetitive patterns of behavior, 
interests, or activities (as specified in Criterion B), which show a range of manifestations 
according to age and ability, intervention, and current 
supports. Stereotyped or repetitive 
behaviors include simple motor stereotypies (e.g., hand flapping, finger flicking), repetitive use 
of objects (e.g., spinning coins, lining up toys), and repetitive speech (e.g., echolalia, the delayed 
or immediate parroting of heard words; 
use of  you  when referring to self; 
stereotyped use of 
words, phrases, or prosodic patterns). Excessive adherence to routines and restricted patterns of 
behavior may be manifest 
in resistance to change (e.g., distress at 
apparently small 
changes, such 
as taking an alternative route to school 
or work; 
insistence on adherence to rules; 
rigidity of 
thinking) or ritualized patterns of verbal 
or nonverbal 
behavior (e.g., repetitive questioning, 
pacing a perimeter). Highly restricted, fixated interests in autism 
spectrum 
disorder tend to be 
abnormal 
in intensity or focus (e.g., a toddler strongly attached to a pan or piece of string; 
a child 
preoccupied with vacuum 


62 


cleaners; 
an adult 
spending hours writing out 
timetables). Some fascinations and routines 
may relate to apparent 
hyper- or hyporeactivity to sensory input, manifested through extreme 
responses to specific sounds or textures, excessive smelling or touching of objects, fascination 



with lights or spinning objects, and sometimes apparent 
indifference to pain, heat, or cold. 
Extreme reaction to or rituals involving taste, smell, texture, or appearance of food or excessive 
food restrictions are common and may be a presenting feature of autism spectrum disorder. 


Many individuals with autism 
spectrum 
disorder without 
intellectual 
or language 
impairments learn to suppress repetitive behavior in public. In these individuals, repetitive 
behaviors like rocking or finger flicking may serve an anxiolytic or self-soothing function. 


Special 
interests may be a source of pleasure and motivation and provide avenues for 
education and employment 
later in life. Diagnostic criteria may be met 
when restricted, repetitive 
patterns of behavior, interests, or activities were clearly present 
during childhood or at 
some time 
in the past, even if symptoms are no longer present. 


Criterion D requires that 
the features must 
cause clinically significant 
impairment 
in social, 
occupational, or other important 
areas of current 
functioning. Criterion E 
specifies that 
the social 
communication deficits, although sometimes accompanied by intellectual 
developmental 
disorder (intellectual 
disability), are not 
in line with the individual s developmental 
level; 
impairments exceed difficulties expected on the basis of developmental level. 


Standardized behavioral 
diagnostic instruments with good psychometric properties, including 
caregiver interviews, questionnaires and clinician observation measures, are available and can 
improve reliability of diagnosis over time and across clinicians. However, the symptoms of 
autism 
spectrum 
disorder occur as dimensions without 
universally accepted cutoff scores for 
what 
would constitute a disorder. Thus, the diagnosis remains a clinical 
one, taking all 
available 
information into account, and is not 
solely dictated by the score on a particular questionnaire or 
observation measure. 


Associated Features 


Many individuals with autism 
spectrum 
disorder also have intellectual 
and/or language 
impairment 
(e.g., slow to talk, language comprehension behind production). Even those with 
average or high intelligence usually have an uneven profile of abilities. The gap between 
intellectual 
and adaptive functional 
skills is often large. It 
is common for individuals with autism 
to have theory-of-mind deficits (i.e., to have difficulty seeing the world from 
another person s 
perspective), but 
these are not 
necessarily present 
in all 
cases. Executive function deficits are 
also common but 
not 
specific, as are difficulties with central 
coherence (i.e., being able to 
understand context or to  see the big picture,  and thus tending to overfocus on detail). 


Motor deficits are often present, including odd gait, clumsiness, and other abnormal 
motor 
signs (e.g., walking on tiptoes). Self-injury (e.g., head banging, biting the wrist) may occur, and 
disruptive/challenging behaviors are more common in children and adolescents with autism 
spectrum 
disorder than other disorders, including intellectual 
developmental 
disorder. Some 
individuals develop catatonic-like motor behavior (slowing and  freezing  mid-action), but 
these 
are typically not 
of the magnitude of a catatonic episode. However, it 
is possible for individuals 
with autism 
spectrum 
disorder to experience a marked deterioration in motor symptoms and 
display a full 
catatonic episode with symptoms such as mutism, posturing, grimacing, and waxy 
flexibility. The risk period for comorbid catatonia appears to be greatest in the adolescent years. 


Prevalence 


Frequencies for autism 
spectrum 
disorder across the United States have been reported to be 



between 1% and 2% of the population, with similar estimates in child and adult 


63 


samples. However, prevalence appears to be lower among U.S. African American (1.1%) and 
Latinx children (0.8%) compared with White children (1.3%), even after the effect 
of 
socioeconomic resources is taken into account. The reported prevalence of autism 
spectrum 
disorder may be affected by misdiagnosis, delayed diagnosis, or underdiagnosis of individuals 
from 
some ethnoracial 
backgrounds. Prevalence across non-U.S. countries has approached 1% of 
the population (0.62% median global 
prevalence), without 
substantial 
variation based on 
geographic region or ethnicity and across child and adult 
samples. Globally, the male:female 
ratio in well-ascertained epidemiological 
samples appears to be 3:1, with concerns about 
underrecognition of autism spectrum disorder in women and girls. 


Development and Course 


The age and pattern of onset 
also should be noted for autism 
spectrum 
disorder. The behavioral 
features of autism 
spectrum 
disorder first 
become evident 
in early childhood, with some cases 
presenting a lack of interest 
in social 
interaction in the first 
year of life. Symptoms are typically 
recognized during the second year of life (age 12 24 months) but 
may be seen earlier than 12 
months if developmental 
delays are severe, or noted later than 24 months if symptoms are more 
subtle. The pattern of onset 
description might 
include information about 
early developmental 
delays or any losses of social 
or language skills. In cases where skills have been lost, parents or 
caregivers may give a history of a gradual 
or relatively rapid deterioration in social 
behaviors or 
language skills. Typically, this would occur between ages 12 and 24 months. 


Prospective studies demonstrate that 
in most 
cases the onset 
of autism 
spectrum 
disorder is 
associated with declines in critical social and communication behaviors in the first 2 years of life. 
Such declines in functioning are rare in other neurodevelopmental 
disorders and may be an 
especially useful 
indicator of the presence of autism 
spectrum 
disorder. In rare cases, there is 
developmental 
regression occurring after at 
least 
2 years of normal 
development 
(previously 
described as childhood disintegrative disorder), which is much more unusual 
and warrants more 
extensive medical 
investigation (i.e., continuous spike and waves during slow-wave sleep 
syndrome and Landau-Kleffner syndrome). Often included in these encephalopathic conditions 
are losses of skills beyond social 
communication (e.g., loss of self-care, toileting, motor skills) 
(see also Rett syndrome in the section  Differential Diagnosis  for this disorder). 


First 
symptoms of autism 
spectrum 
disorder frequently involve delayed language 
development, often accompanied by lack of social 
interest 
or unusual 
social 
interactions (e.g., 
pulling individuals by the hand without 
any attempt 
to look at 
them), odd play patterns (e.g., 
carrying toys around but 
never playing with them), and unusual 
communication patterns (e.g., 
knowing the alphabet 
but 
not 
responding to own name). Deafness may be suspected but 
is 
typically ruled out. During the second year, odd and repetitive behaviors and the absence of 
typical 
play become more apparent. Since many typically developing young children have strong 
preferences and enjoy repetition (e.g., eating the same foods, watching the same video multiple 
times), distinguishing restricted and repetitive behaviors that 
are diagnostic of autism 
spectrum 
disorder can be difficult 
in preschoolers. The clinical 
distinction is based on the type, frequency, 
and intensity of the behavior (e.g., a child who daily lines up objects for hours and is very 



distressed if any item is moved). 


Autism 
spectrum 
disorder is not 
a degenerative disorder, and it 
is typical 
for learning and 
compensation to continue throughout 
life. Symptoms are often most 
marked in early childhood 
and early school 
years, with developmental 
gains typical 
in later childhood in at 
least 
some areas 
(e.g., increased interest 
in social 
interaction). A small 
proportion of individuals deteriorate 
behaviorally during adolescence, whereas most 
others improve. While it 
was once the case that 
only a minority of individuals with autism 
spectrum 
disorder lived and worked independently in 
adulthood, as diagnosis of autism spectrum 


64 


disorder is made more frequently in those who have superior language and intellectual 
abilities, more individuals are able to find a niche that 
matches their special 
interests and skills 
and thus are productively employed. Access to vocational 
rehabilitation services significantly 
improves competitive employment 
outcomes for transition-age youth with autism 
spectrum 
disorder. 


In general, individuals with lower levels of impairment 
may be better able to function 
independently. However, even these individuals may remain socially naive and vulnerable, have 
difficulties organizing practical 
demands without 
aid, and are prone to anxiety and depression. 
Many adults report 
using compensation strategies and coping mechanisms to mask their 
difficulties in public but 
suffer from 
the stress and effort 
of maintaining a socially acceptable 
facade. Relatively little is known about 
old age in autism 
spectrum 
disorder, but 
higher rates of 
co-occurring medical conditions have been documented in the literature. 


Some individuals come for first diagnosis in adulthood, perhaps prompted by the diagnosis of 
autism 
in a child in the family or a breakdown of relations at 
work or home. Obtaining detailed 
developmental 
history in such cases may be difficult, and it 
is important 
to consider self-reported 
difficulties. Where clinical 
observation suggests criteria are currently met, autism 
spectrum 
disorder may be diagnosed, particularly if supported by a history of poor social 
and 
communication skills in childhood. A compelling report 
(by parents or another relative) that 
the 
individual 
had ordinary and sustained reciprocal 
friendships and good nonverbal 
communication 
skills throughout 
childhood would significantly lessen the likelihood of a diagnosis of autism 
spectrum 
disorder; 
however, ambiguous or absent 
developmental 
information in itself is not 
sufficient to rule out a diagnosis of autism spectrum disorder. 


Manifestations of the social 
and communication impairments and restricted/repetitive 
behaviors that 
define autism 
spectrum 
disorder are clear in the developmental 
period. In later 
life, intervention or compensation, as well 
as current 
supports, may mask these difficulties in at 
least 
some contexts. Overall, symptoms remain sufficient 
to cause current 
impairment 
in social, 
occupational, or other important areas of functioning. 


Risk and Prognostic Factors 


The best 
established prognostic factors for individual 
outcome within autism 
spectrum 
disorder 
are presence or absence of associated intellectual 
developmental 
disorder and language 
impairment 
(e.g., functional 
language by age 5 years is a good prognostic sign) and additional 
mental 
health problems. Epilepsy, as a comorbid diagnosis, is associated with greater intellectual 
disability and lower verbal ability. 



Environmental. 
A variety of risk factors for neurodevelopmental 
disorders, such as advanced 
parental 
age, extreme prematurity, or in utero exposures to certain drugs or teratogens like 
valproic acid, may broadly contribute to risk of autism spectrum disorder. 


Genetic 
and 
physiological. 
Heritability estimates for autism 
spectrum 
disorder have ranged from 
37% to higher than 90%, based on twin concordance rates, and a more recent 
five-country cohort 
estimated heritability at 
80%. Currently, as many as 15% of cases of autism 
spectrum 
disorder 
appear to be associated with a known genetic mutation, with different 
de novo copy number 
variants or de novo mutations in specific genes associated with the disorder in different 
families. 
However, even when a known genetic mutation is associated with autism 
spectrum 
disorder, it 
does not 
appear to be fully penetrant 
(i.e., not 
all 
individuals with that 
same genetic abnormality 
will 
develop autism 
spectrum 
disorder). Risk for the majority of cases appears to be polygenic, 
with perhaps hundreds of genetic loci 
making relatively small 
contributions. Whether these 
findings apply to all 
racial/ethnic populations equally is unclear, given the limited inclusion of 
communities of color in genetic research. 


65 


Culture-Related Diagnostic Issues 


Cultural 
differences exist 
in norms for social 
interaction, nonverbal 
communication, and 
relationships, but 
individuals with autism 
spectrum 
disorder are markedly impaired against 
the 
norms for their cultural 
context. Culture influences the perception of autistic behaviors, the 
perceived salience of some behaviors over others, and the expectations for child behavior and 
parenting practices. Considerable discrepancies are found in age at 
diagnosis of autism 
spectrum 
disorder in children from 
diverse ethnoracial 
backgrounds; 
most 
studies find delayed diagnosis 
among socially oppressed ethnic and racialized children. In addition to being diagnosed later, 
African American children are more often misdiagnosed with adjustment 
or conduct 
disorder 
than are White children. 


Sex- and Gender-Related Diagnostic Issues 


Autism 
spectrum 
disorder is diagnosed three to four times more often in males than in females, 
and on average, age at 
diagnosis is later in females. In clinic samples, females tend to be more 
likely to show accompanying intellectual 
developmental 
disorder as well 
as epilepsy, suggesting 
that 
girls without 
intellectual 
impairments or language delays may go unrecognized, perhaps 
because of subtler manifestation of social 
and communication difficulties. In comparison with 
males with autism 
spectrum 
disorder, females may have better reciprocal 
conversation, and be 
more likely to share interests, to integrate verbal 
and nonverbal 
behavior, and to modify their 
behavior by situation, despite having similar social 
understanding difficulties as males. 
Attempting to hide or mask autistic behavior (e.g., by copying the dress, voice, and manner of 
socially successful 
women) may also make diagnosis harder in some females. Repetitive 
behaviors may be somewhat 
less evident 
in females than in males, on average, and special 
interests may have a more social 
(e.g., a singer, an actor) or  normative  focus (e.g., horses), 
while remaining unusual 
in their intensity. Relative to the general 
population, rates of gender 
variance have been reported to be increased in autism 
spectrum 
disorder, with higher variance in 
females compared with males. 



Association With Suicidal 
Thoughts or Behavior 


Individuals with autism 
spectrum 
disorder are at 
greater risk for suicide death compared with 
those without 
autism 
spectrum 
disorder. Children with autism 
spectrum 
disorder who had 
impaired social 
communication had a higher risk of self-harm 
with suicidal 
intent, suicidal 
thoughts, and suicide plans by age 16 years as compared with those without 
impaired social 
communication. Adolescents and young adults with autism 
spectrum 
disorder have an increased 
risk of suicide attempts compared with age-and sex-matched control 
subjects, even after 
adjustments for demographic factors and psychiatric comorbidities. 


Functional 
Consequences of Autism Spectrum Disorder 


In young children with autism 
spectrum 
disorder, lack of social 
and communication abilities may 
hamper learning, especially learning through social 
interaction or in settings with peers. In the 
home, insistence on routines and aversion to change, as well 
as sensory sensitivities, may 
interfere with eating and sleeping and make routine care (e.g., haircuts, dental 
work) extremely 
difficult. Adaptive skills are typically below measured IQ. Extreme difficulties in planning, 
organization, and coping with change negatively impact 
academic achievement, even for 
students with above-average intelligence. During adulthood, these individuals may have 
difficulties establishing independence because of continued rigidity and difficulty with novelty. 


Many individuals with autism 
spectrum 
disorder, even without 
intellectual 
developmental 
disorder, have poor adult psychosocial functioning as indexed by measures such 


66 


as independent 
living and gainful 
employment. Functional 
consequences in old age are 
unknown, but 
social 
isolation and communication problems (e.g., reduced help-seeking) are 
likely to have consequences for health in older adulthood. 


Co-occurring intellectual 
developmental 
disorder, epilepsy, mental 
disorders, and chronic 
medical 
conditions may be associated with a higher risk of premature mortality for individuals 
with autism 
spectrum 
disorder. Deaths from 
injury and poisoning are higher than for the general 
population, as are deaths from 
suicide. Drowning is the leading cause of accidental 
death in 
children with autism spectrum disorder. 


Differential 
Diagnosis 


Attention-deficit/hyperactivity 
disorder. 
Abnormalities of attention (overly focused or easily 
distracted) are common in individuals with autism 
spectrum 
disorder, as is hyperactivity. 
Moreover, some individuals with ADHD may exhibit 
social 
communication deficits such as 
interrupting others, speaking too loudly, and not 
respecting personal 
space. Although potentially 
difficult 
to discriminate ADHD from 
autism 
spectrum 
disorder, the developmental 
course and 
absence of restricted, repetitive behaviors and unusual 
interests in ADHD help in differentiating 
the two conditions. A concurrent 
diagnosis of ADHD should be considered when attentional 
difficulties or hyperactivity exceeds that 
typically seen in individuals of comparable mental 
age, 
and ADHD is one of the most common comorbidities in autism spectrum disorder. 


Intellectual 
developmental 
disorder (intellectual 
disability) 
without 
autism spectrum disorder. 


Intellectual 
developmental 
disorder without 
autism 
spectrum 
disorder may be difficult 
to differentiate from 



autism 
spectrum 
disorder in very young children. Individuals with intellectual 
developmental 
disorder who have not 
developed language or symbolic skills also present 
a challenge for 
differential 
diagnosis, since repetitive behavior often occurs in such individuals as well. A 
diagnosis of autism 
spectrum 
disorder in an individual 
with intellectual 
developmental 
disorder 
is appropriate when social 
communication and interaction are significantly impaired relative to 
the developmental 
level 
of the individual s nonverbal 
skills (e.g., fine motor skills, nonverbal 
problem 
solving). In contrast, intellectual 
developmental 
disorder is the appropriate diagnosis 
when there is no apparent discrepancy between the level of social communicative skills and other 
intellectual skills. 
Language 
disorders 
and 
social 
(pragmatic) 
communication 
disorder. 
In some forms of language 


disorder, there may be problems of communication and some secondary social 
difficulties. 
However, specific language disorder is not 
usually associated with abnormal 
nonverbal 
communication, nor with the presence of restricted, repetitive patterns of behavior, interests, or 
activities. 


When an individual 
shows impairment 
in social 
communication and social 
interactions but 
does not 
show restricted and repetitive behavior or interests, criteria for social 
(pragmatic) 
communication disorder, instead of autism 
spectrum 
disorder, may be met. The diagnosis of 
autism 
spectrum 
disorder supersedes that 
of social 
(pragmatic) communication disorder 
whenever the criteria for autism 
spectrum 
disorder are met, and care should be taken to enquire 
carefully regarding past or current restricted/repetitive behavior. 


Selective 
mutism. 
In selective mutism, early development 
is not 
typically disturbed. The affected 
child usually exhibits appropriate communication skills in certain contexts and settings. Even in 
settings where the child is mute, 
social 
reciprocity is not 
impaired, nor are restricted or repetitive 
patterns of behavior present. 


Stereotypic 
movement 
disorder. 
Motor stereotypies are among the diagnostic characteristics of 
autism 
spectrum 
disorder, so an additional 
diagnosis of stereotypic movement 
disorder is not 
given when such repetitive behaviors are better explained by the presence 


67 


of autism 
spectrum 
disorder. However, when stereotypies cause self-injury and become a focus 


of treatment, both diagnoses may be appropriate. 
Rett 
syndrome. 
Disruption of social 
interaction may be observed during the regressive phase of 
Rett 
syndrome (typically between ages 1 and 4 years); 
thus, a substantial 
proportion of affected 
young girls may have a presentation that 
meets diagnostic criteria for autism 
spectrum 
disorder. 
However, after this period, most 
individuals with Rett 
syndrome improve their social 
communication skills, and autistic features are no longer a major area of concern. Consequently, 
autism spectrum disorder should be considered only when all diagnostic criteria are met. 


Symptoms 
associated 
with 
anxiety 
disorders. 
The overlap of anxiety symptoms with the core 
symptoms of autism 
spectrum 
disorder can make the classification of anxiety symptoms in 
autism 
spectrum 
disorder challenging. For example, social 
withdrawal 
and repetitive behaviors 
are core features of autism 
spectrum 
disorder but 
may also be expressions of anxiety. The most 
common anxiety disorders in autism 
spectrum 
disorder are specific phobia (in up to 30% of 
cases), and social anxiety and agoraphobia (in as many as 17% of cases). 



Obsessive-compulsive 
disorder. 
Repetitive behavior is a defining feature of both obsessive-
compulsive disorder and autism 
spectrum 
disorder. In both conditions, repetitive behaviors are 
considered to be inappropriate or odd. In obsessive-compulsive disorder, intrusive thoughts are 
often related to contamination, organization, or sexual 
or religious themes. Compulsions are 
performed in response to these intrusive thoughts in attempts to relieve anxiety. In autism 
spectrum 
disorder, repetitive behaviors classically include more stereotyped motor behaviors, 
such as hand flapping and finger shaking or more complex behaviors, such as insistence on 
routines or lining up objects. Contrary to obsessive-compulsive disorder, repetitive behaviors in 
autism spectrum disorder may be perceived as pleasurable and reinforcing. 


Schizophrenia. 
Schizophrenia with childhood onset 
usually develops after a period of normal, or 
near normal, development. A prodromal 
state has been described in which social 
impairment 
and 
atypical 
interests and beliefs occur, which could be confused with the social 
deficits and 
restricted fixated interests seen in autism 
spectrum 
disorder. Hallucinations and delusions, which 
are defining features of schizophrenia, are not 
features of autism 
spectrum 
disorder. However, 
clinicians must 
take into account 
the potential 
for individuals with autism 
spectrum 
disorder to 
be concrete in their interpretation of questions regarding the key features of schizophrenia (e.g., 
 Do you hear voices when no one is there?   Yes [on the radio] ). Autism 
spectrum 
disorder and 
schizophrenia can co-occur, and both should be diagnosed when criteria are met. 


Personality 
disorders. 
In adults without 
intellectual 
developmental 
disorder or significant 
language impairment, some behaviors associated with autism 
spectrum 
disorder may be 
perceived by others as symptoms of narcissistic, schizotypal, or schizoid personality disorder. 
Schizotypal 
personality disorder in particular may intersect 
with autism 
spectrum 
disorder in 
unusual 
preoccupations and perceptual 
experiences, odd thinking and speech, constricted affect 
and social 
anxiety, lack of close friends, and odd or eccentric behavior. The early developmental 
course of autism 
spectrum 
disorder (lack of imaginative play, restricted/repetitive behavior, 
sensory sensitivities) is most helpful in differentiating it from personality disorders. 


Comorbidity 


Autism 
spectrum 
disorder is frequently associated with intellectual 
developmental 
disorder and 
language disorder (i.e., an inability to comprehend and construct 
sentences with proper 
grammar). Specific learning difficulties (literacy and numeracy) are common, as is 
developmental coordination disorder. 


68 


Psychiatric comorbidities also co-occur in autism 
spectrum 
disorder. About 
70% of 
individuals with autism 
spectrum 
disorder may have one comorbid mental 
disorder, and 40% 
may have two or more comorbid mental 
disorders. Anxiety disorders, depression, and ADHD are 
particularly common. Avoidant/restrictive food intake disorder is a fairly frequent 
presenting 
feature of autism spectrum disorder, and extreme and narrow food preferences may persist. 


Among individuals who are nonverbal 
or have language deficits, observable signs such as 
changes in sleep or eating and increases in challenging behavior should trigger an evaluation for 
anxiety or depression, as well 
as for potential 
pain or discomfort 
from 
undiagnosed medical 
or 
dental 
problems. Medical 
conditions commonly associated with autism 
spectrum 
disorder 



include epilepsy and constipation. 


Attention-Deficit/Hyperactivity Disorder 


Attention-Deficit/Hyperactivity Disorder 


Diagnostic Criteria 


A. 
A 
persistent 
pattern 
of 
inattention 
and/or hyperactivity-impulsivity that 
interferes 
with 
functioning 
or development, 
as characterized 
by (1) and/or (2): 
1. 
Inattention: 
Six (or more) of 
the 
following 
symptoms have 
persisted 
for at 
least 
6 
months to 
a 
degree 
that 
is inconsistent 
with 
developmental level and 
that 
negatively impacts directly on 
social and 
academic/occupational 
activities: 
Note: 
The 
symptoms are 
not 
solely a 
manifestation 
of 
oppositional behavior, 
defiance, 
hostility, 
or failure 
to 
understand 
tasks or instructions. 
For older 
adolescents and 
adults (age 
17 
and 
older), 
at 
least 
five 
symptoms are 
required. 


a. 
Often 
fails to 
give 
close 
attention 
to 
details or makes careless mistakes in 
schoolwork, 
at 
work, 
or during 
other activities (e.g., 
overlooks or misses 
details, 
work is inaccurate). 
b. 
Often 
has difficulty sustaining 
attention 
in 
tasks or play activities (e.g., 
has 
difficulty remaining 
focused 
during 
lectures, 
conversations, 
or lengthy 
reading). 
c. 
Often 
does not 
seem to 
listen 
when 
spoken 
to 
directly (e.g., 
mind 
seems 
elsewhere, 
even 
in 
the 
absence 
of 
any obvious distraction). 
d. 
Often 
does not 
follow through 
on 
instructions and 
fails to 
finish 
schoolwork, 
chores, 
or duties in 
the 
workplace 
(e.g., 
starts tasks but 
quickly loses focus and 
is easily sidetracked). 
e. 
Often 
has difficulty organizing 
tasks and 
activities (e.g., 
difficulty managing 
sequential tasks; 
difficulty keeping 
materials and 
belongings in 
order; 
messy, 
disorganized 
work; 
has poor time 
management; 
fails to 
meet 
deadlines). 
f. 
Often 
avoids, 
dislikes, 
or is reluctant 
to 
engage 
in 
tasks that 
require 
sustained 
mental effort 
(e.g., 
schoolwork or homework; 
for older 
adolescents and 
adults, 
preparing 
reports, 
completing 
forms, 
reviewing 
lengthy papers). 
g. 
Often 
loses things necessary for tasks or activities (e.g., 
school materials, 
pencils, 
books, 
tools, 
wallets, 
keys, 
paperwork, 
eyeglasses, 
mobile 

telephones). 


69 


h. 
Is often 
easily distracted 
by extraneous stimuli (for older adolescents and 
adults, 
may include 
unrelated 
thoughts). 
i. 
Is often 
forgetful in 
daily activities (e.g., 
doing 
chores, 
running 
errands; 
for 
older adolescents and 
adults, 
returning 
calls, 
paying 
bills, 
keeping 
appointments). 
2. 
Hyperactivity 
and 
impulsivity: 
Six (or more) of 
the 
following 
symptoms 
have 
persisted 
for at 
least 
6 
months to 
a 
degree 
that 
is inconsistent 
with 
developmental level and 
that 
negatively impacts directly on 
social and 
academic/occupational activities: 
Note: 
The 
symptoms are 
not 
solely a 
manifestation 
of 
oppositional behavior, 
defiance, 
hostility, 
or a 
failure 
to 
understand 
tasks or instructions. 
For older 
adolescents and 
adults (age 
17 
and 
older), 
at 
least 
five 
symptoms are 
required. 


a. 
Often 
fidgets with 
or taps hands or feet 
or squirms in 
seat. 
b. 
Often 
leaves seat 
in 
situations when 
remaining 
seated 
is expected 
(e.g., 
leaves his or her place 
in 
the 
classroom, 
in 
the 
office 
or other workplace, 
or in 
other situations that 
require 
remaining 
in 
place). 
c. 
Often 
runs about 
or climbs in 
situations where 
it 
is inappropriate. 
(Note: 
In 
adolescents or adults, 
may be 
limited 
to 
feeling 
restless.) 
d. 
Often 
unable 
to 
play or engage 
in 
leisure 
activities quietly. 
e. 
Is often 
 on 
the 
go,  acting 
as if 
 driven 
by a 
motor  (e.g., 
is unable 
to 
be 
or 
uncomfortable 
being 
still for extended 
time, 
as in 
restaurants, 
meetings; 
may be 
experienced 
by others as being 
restless or difficult 
to 
keep 
up 
with). 
f. 
Often 
talks excessively. 
g. 
Often 
blurts out 
an 
answer before 
a 
question 
has been 
completed 
(e.g., 
completes people s sentences; 
cannot 
wait 
for turn 
in 
conversation). 
h. 
Often 
has difficulty waiting 
his or her turn 
(e.g., 
while 
waiting 
in 
line). 
i. 
Often 
interrupts or intrudes on 
others (e.g., 
butts into 
conversations, 
games, 
or activities; 
may start 
using 
other people s things without 
asking 
or receiving 
permission; 
for adolescents and 
adults, 
may intrude 
into 
or 
take 
over what 
others are 
doing). 
B. 
Several inattentive 
or hyperactive-impulsive 
symptoms were 
present 
prior to 
age 
12 
years. 
C. 
Several inattentive 
or hyperactive-impulsive 
symptoms are 
present 
in 
two 
or 
more 
settings (e.g., 
at 
home, 
school, 
or work; 
with 
friends or relatives; 
in 
other 
activities). 
D. 
There 
is clear evidence 
that 
the 
symptoms interfere 
with, 
or reduce 
the 
quality of, 

social, 
academic, 
or occupational functioning. 


E. 
The 
symptoms do 
not 
occur exclusively during 
the 
course 
of 
schizophrenia 
or 
another psychotic disorder and 
are 
not 
better explained 
by another mental 
disorder (e.g., 
mood 
disorder, 
anxiety disorder, 
dissociative 
disorder, 
personality 
disorder, 
substance 
intoxication 
or withdrawal). 
Specify 
whether: 


F90.2 
Combined 
presentation: 
If 
both 
Criterion 
A1 
(inattention) and 
Criterion 
A2 
(hyperactivity-impulsivity) are 
met 
for the 
past 
6 
months. 
F90.0 
Predominantly 
inattentive 
presentation: 
If 
Criterion 
A1 
(inattention) is 


met 
but 
Criterion 
A2 
(hyperactivity-impulsivity) is not 
met 
for the 
past 
6 
months. 
F90.1 
Predominantly 
hyperactive/impulsive 
presentation: 
If 
Criterion 
A2 
(hyperactivity-impulsivity) is met 
and 
Criterion 
A1 
(inattention) is not 
met 
for the 
past 
6 
months. 
Specify 
if: 
In 
partial 
remission: 
When 
full criteria 
were 
previously met, 
fewer than 
the 
full 
criteria 
have 
been 
met 
for the 
past 
6 
months, 
and 
the 
symptoms still result 
in 
impairment 
in 
social, 
academic, 
or occupational functioning. 


70 


Specify 
current 
severity: 
Mild: 
Few, 
if 
any, 
symptoms in 
excess of 
those 
required 
to 
make 
the 
diagnosis 


are 
present, 
and 
symptoms result 
in 
no 
more 
than 
minor impairments in 
social or 
occupational functioning. 
Moderate: 
Symptoms or functional impairment 
between 
 mild  and 
 severe  are 


present. 
Severe: 
Many symptoms in 
excess of 
those 
required 
to 
make 
the 
diagnosis, 
or 
several symptoms that 
are 
particularly severe, 
are 
present, 
or the 
symptoms 
result 
in 
marked 
impairment 
in 
social or occupational functioning. 


Diagnostic Features 


The essential 
feature of attention-deficit/hyperactivity disorder (ADHD) is a persistent 
pattern of 
inattention and/or hyperactivity-impulsivity that 
interferes with functioning or development. 
Inattention 
manifests behaviorally in ADHD as wandering off task, failing to follow through on 
instructions or finishing work or chores, having difficulty sustaining focus, and being 
disorganized and is not 
attributable to defiance or lack of comprehension. Hyperactivity 
refers to 
excessive motor activity (such as a child running about) when it 
is not 
appropriate, or excessive 
fidgeting, tapping, or talkativeness. In adults, hyperactivity may manifest 
as extreme restlessness 
or wearing others out 
with their activity. Impulsivity 
refers to hasty actions that 
occur in the 
moment 
without 
forethought, which may have potential 
for harm 
to the individual 
(e.g., darting 
into the street 
without 
looking). Impulsivity may reflect 
a desire for immediate rewards or an 
inability to delay gratification. Impulsive behaviors may manifest 
as social 
intrusiveness (e.g., 



interrupting others excessively) and/or as making important 
decisions without 
consideration of 
long-term consequences (e.g., taking a job without adequate information). 


ADHD begins in childhood. The requirement 
that 
several 
symptoms be present 
before age 12 
years conveys the importance of a substantial 
clinical 
presentation during childhood. At 
the same 
time, an earlier age at 
onset 
is not 
specified because of difficulties in establishing precise 
childhood onset 
retrospectively. Adult 
recall 
of childhood symptoms tends to be unreliable, and 
it 
is beneficial 
to obtain ancillary information. ADHD cannot 
be diagnosed in the absence of any 
symptoms prior to age 12. When symptoms of what appears to be ADHD first occur after age 13, 
they are more likely to be explained by another mental 
disorder or to represent 
the cognitive 
effects of substance use. 


Manifestations of the disorder must 
be present 
in more than one setting (e.g., home and 
school, or home and work). Confirmation of substantial 
symptoms across settings typically 
cannot 
be done accurately without 
consulting informants who have seen the individual 
in those 
settings. Typically, symptoms vary depending on context 
within a given setting. Signs of the 
disorder may be minimal 
or absent 
when the individual 
is receiving frequent 
rewards for 
appropriate behavior, is under close supervision, is in a novel 
setting, is engaged in especially 
interesting activities, has consistent 
external 
stimulation (e.g., via electronic screens), or is 
interacting in one-on-one situations (e.g., the clinician's office). 


Associated Features 


Delays in language, motor, or social 
development 
are not 
specific to ADHD but 
often co-occur. 
Emotional 
dysregulation or emotional 
impulsivity commonly occurs in children and adults with 
ADHD. Individuals with ADHD self-report 
and are described by others as being quick to anger, 
easily frustrated, and overreactive emotionally. 


Even in the absence of a specific learning disorder, academic or work performance is often 
impaired. Individuals with ADHD may exhibit 
neurocognitive deficits in a variety of areas, 
including working memory, set 
shifting, reaction time variability, response inhibition, vigilance, 
and planning/organization, although these tests are not 
sufficiently sensitive or specific to serve 
as diagnostic indices. 


71 


Although ADHD is not 
associated with specific physical 
features, rates of minor physical 
anomalies (e.g., hypertelorism, highly arched palate, low-set 
ears) may be elevated. Subtle motor 
delays and other neurological 
soft 
signs may occur. (Note that 
marked co-occurring clumsiness 
and motor delays should be coded separately [e.g., developmental coordination disorder].) 


Children with neurodevelopmental 
disorders with a known cause (e.g., fragile X syndrome, 
22q11 deletion syndrome) may often also have symptoms of inattention and 
impulsivity/hyperactivity; 
they should receive an ADHD diagnosis if their symptoms meet 
the 
full criteria for the disorder. 


Prevalence 


Population surveys suggest 
that 
ADHD occurs worldwide in about 
7.2% of children; 
however, 
cross-national 
prevalence ranges widely, from 
0.1% to 10.2% of children and adolescents. 
Prevalence is higher in special 
populations such as foster children or correctional 
settings. In a 



cross-national meta-analysis, ADHD occurred in 2.5% of adults. 


Development and Course 


Many parents first 
observe excessive motor activity when the child is a toddler, but 
symptoms 
are difficult 
to distinguish from 
highly variable normative behaviors before age 4 years. ADHD 
is most 
often identified during elementary school 
years when inattention becomes more 
prominent 
and impairing. The disorder is relatively stable through early adolescence, but 
some 
individuals have a worsened course with development 
of antisocial 
behaviors. In most 
individuals with ADHD, symptoms of motoric hyperactivity become less obvious in adolescence 
and adulthood, but 
difficulties with restlessness, inattention, poor planning, and impulsivity 
persist. A substantial 
proportion of children with ADHD remain relatively impaired into 
adulthood. 


In preschool, the main manifestation is hyperactivity. Inattention becomes more prominent 
during elementary school. During adolescence, signs of hyperactivity (e.g., running and 
climbing) are less common and may be confined to fidgetiness or an inner feeling of jitteriness, 
restlessness, or impatience. In adulthood, along with inattention and restlessness, impulsivity 
may remain problematic even when hyperactivity has diminished. 


Risk and Prognostic Factors 


Temperamental. 


ADHD is associated with reduced behavioral 
inhibition, effortful 
control, or 
constraint; 
negative emotionality; 
and/or elevated novelty seeking. These traits may predispose 
some children to ADHD but are not specific to the disorder. 


Environmental. 
Very low birth weight 
and degree of prematurity convey a greater risk for 
ADHD; 
the more extreme the low weight, the greater the risk. Prenatal 
exposure to smoking is 
associated with ADHD even after controlling for parental 
psychiatric history and socioeconomic 
status. A minority of cases may be related to reactions to aspects of diet. Neurotoxin exposure 
(e.g., lead), infections (e.g., encephalitis), and alcohol 
exposure in utero have been correlated 
with subsequent ADHD, but it is not known whether these associations are causal. 


Genetic 
and 
physiological. 
The heritability of ADHD is approximately 74%. Large-scale genome-
wide association studies (GWAS) have identified a number of loci 
enriched in evolutionarily 
constrained genomic regions and loss-of-function genes as well 
as around brain-expressed 
regulatory regions. There is no single gene for ADHD. 


Visual 
and hearing impairments, metabolic abnormalities, and nutritional 
deficiencies should 
be considered as possible influences on ADHD symptoms. ADHD is elevated in individuals with 
idiopathic epilepsy. 


72 


Course 
modifiers. 
Family interaction patterns in early childhood are unlikely to cause ADHD but 
may influence its course or contribute to secondary development of conduct problems. 


Culture-Related Diagnostic Issues 


Differences in ADHD prevalence across regions appear attributable mainly to different 
diagnostic procedures and methodological 
practices, including using different 
diagnostic 



int 
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101 



Schizophrenia Spectrum and Other Psychotic 
Disorders 


Schizophrenia spectrum 
and other psychotic disorders include schizophrenia, other 
psychotic disorders, and schizotypal 
(personality) disorder. They are defined by abnormalities in 
one or more of the following five domains: 
delusions, hallucinations, disorganized thinking 
(speech), grossly disorganized or abnormal 
motor behavior (including catatonia), and negative 
symptoms. 


Key Features That 
Define the Psychotic Disorders 


Delusions 


Delusions 
are fixed beliefs that 
are not 
amenable to change in light 
of conflicting evidence. Their 
content 
may include a variety of themes (e.g., persecutory, referential, somatic, religious, 
grandiose). Persecutory delusions 
(i.e., belief that 
one is going to be harmed, harassed, and so 
forth by an individual, organization, or other group) are most 
common. Referential 
delusions 
(i.e., belief that 
certain gestures, comments, environmental 
cues, and so forth are directed at 
oneself) are also common. Grandiose delusions 
(i.e., when an individual 
believes that 
he or she 
has exceptional 
abilities, wealth, or fame) and erotomanic delusions 
(i.e., when an individual 
believes falsely that 
another person is in love with him 
or her) are also seen. Nihilistic delusions 
involve the conviction that 
a major catastrophe will 
occur, and somatic delusions 
focus on 
preoccupations regarding health and organ function. 


Delusions are deemed bizarre 
if they are clearly implausible and not 
understandable to same-
culture peers and do not 
derive from 
ordinary life experiences. An example of a bizarre delusion 
is the belief that 
an outside force has removed his or her internal 
organs and replaced them 
with 
someone else s organs without 
leaving any wounds or scars. An example of a nonbizarre 
delusion is the belief that 
one is under surveillance by the police, despite a lack of convincing 
evidence. Delusions that 
express a loss of control 
over mind or body are generally considered to 
be bizarre; 
these include the belief that 
one s thoughts have been  removed  by some outside 
force (thought 
withdrawal), that 
alien thoughts have been put 
into one s mind (thought 
insertion), or that 
one s body or actions are being acted on or manipulated by some outside force 
(delusions of control). 


The distinction between a delusion and a strongly held idea is sometimes difficult 
to 
determine and depends in part 
on the degree of conviction with which the belief is held despite 
clear or reasonable contradictory evidence regarding its veracity. Assessing delusions in 
individuals from 
a variety of cultural 
backgrounds can be difficult. Some religious and 
supernatural 
beliefs (e.g., evil 
eye, causing illness through curses, influence of spirits) may be 
viewed as bizarre and possibly delusional 
in some cultural 
contexts but 
be generally accepted in 



others. However, elevated religiosity can be a feature of many presentations of psychosis. 


Individuals who have experienced torture, political 
violence, or discrimination can report 
fears that 
may be misjudged as persecutory delusions; 
these may represent 
instead intense fears 
of recurrence or posttraumatic symptoms. A careful evaluation of whether the 


102 


person s fears are justified given the nature of the trauma can help to differentiate appropriate 
fears from persecutory delusions. 


Hallucinations 


Hallucinations 
are perception-like experiences that 
occur without 
an external 
stimulus. They are 
vivid and clear, with the full 
force and impact 
of normal 
perceptions, and not 
under voluntary 
control. They may occur in any sensory modality, but 
auditory hallucinations are the most 
common in schizophrenia and related disorders. Auditory hallucinations are usually experienced 
as voices, whether familiar or unfamiliar, that 
are perceived as distinct 
from 
the individual s own 
thoughts. The hallucinations must 
occur in the context 
of a clear sensorium; 
those that 
occur 
while falling asleep (hypnagogic) or waking up (hypnopompic) are considered to be within the 
range of normal 
experience. Hallucinations may be a normal 
part 
of religious experience in 
certain cultural contexts. 


Disorganized Thinking (Speech) 


Disorganized thinking 
(formal 
thought 
disorder) is typically inferred from 
the individual s 
speech. The individual 
may switch from 
one topic to another (derailment 
or loose associations). 
Answers to questions may be obliquely related or completely unrelated (tangentiality). Rarely, 
speech may be so severely disorganized that 
it 
is nearly incomprehensible and resembles 
receptive aphasia in its linguistic disorganization (incoherence 
or  word salad ). Because mildly 
disorganized speech is common and nonspecific, the symptom 
must 
be severe enough to 
substantially impair effective communication. The severity of the impairment 
may be difficult 
to 
evaluate if the person making the diagnosis comes from 
a different 
linguistic background than 
that 
of the person being examined. For example, some religious groups engage in glossolalia 
( speaking in tongues ); 
others describe experiences of possession trance (trance states in which 
personal 
identity is replaced by an external 
possessing identity). These phenomena are 
characterized by disorganized speech. These instances do not 
represent 
signs of psychosis unless 
they are accompanied by other clearly psychotic symptoms. Less severe disorganized thinking or 
speech may occur during the prodromal and residual periods of schizophrenia. 


Grossly Disorganized or Abnormal 
Motor Behavior (Including 
Catatonia) 


Grossly disorganized or abnormal 
motor behavior 
may manifest 
itself in a variety of ways, 
ranging from 
childlike  silliness  to unpredictable agitation. Problems may be noted in any form 
of goal-directed behavior, leading to difficulties in performing activities of daily living. 


Catatonic behavior 
is a marked decrease in reactivity to the environment. This ranges from 
resistance to instructions (negativism); 
to maintaining a rigid, inappropriate or bizarre posture; 
to 
a complete lack of verbal 
and motor responses (mutism 
and stupor). It 
can also include 



purposeless and excessive motor activity without 
obvious cause (catatonic excitement). Other 
features are repeated stereotyped movements, staring, grimacing, and the echoing of speech. 
Although catatonia has historically been associated with schizophrenia, catatonic symptoms are 
nonspecific and may occur in other mental 
disorders (e.g., bipolar or depressive disorders with 
catatonia) and in medical conditions (catatonic disorder due to another medical condition). 


Negative Symptoms 


Negative symptoms 
account 
for a substantial 
portion of the morbidity associated with 
schizophrenia but 
are less prominent 
in other psychotic disorders. Two negative symptoms are 
particularly prominent 
in schizophrenia: 
diminished emotional 
expression and avolition. 
Diminished emotional expression includes reductions in the expression of emotions in the 


103 


face, eye contact, intonation of speech (prosody), and movements of the hand, head, and face that 
normally give an emotional 
emphasis to speech. Avolition 
is a decrease in motivated self-
initiated purposeful 
activities. The individual 
may sit 
for long periods of time and show little 
interest 
in participating in work or social 
activities. Other negative symptoms include alogia, 
anhedonia, and asociality. Alogia 
is manifested by diminished speech output. Anhedonia 
is the 
decreased ability to experience pleasure. Individuals with schizophrenia can still 
enjoy a 
pleasurable activity in the moment 
and can recall 
it, but 
show a reduction in the frequency of 
engaging in pleasurable activity. Asociality 
refers to the apparent 
lack of interest 
in social 
interactions and may be associated with avolition, but 
it 
can also be a manifestation of limited 
opportunities for social interactions. 


Disorders in This Chapter 


This chapter is organized along a gradient 
of psychopathology. Clinicians should first 
consider 
conditions that 
do not 
reach full 
criteria for a psychotic disorder or are limited to one domain of 
psychopathology. Then they should consider time-limited conditions. Finally, the diagnosis of a 
schizophrenia spectrum 
disorder requires the exclusion of another condition that 
may give rise to 
psychosis. 


Schizotypal 
personality disorder is noted within this chapter as it 
is considered within the 
schizophrenia spectrum, although its full 
description is found in the chapter  Personality 
Disorders.  The diagnosis schizotypal 
personality disorder captures a pervasive pattern of social 
and interpersonal 
deficits, including reduced capacity for close relationships; 
cognitive or 
perceptual 
distortions; 
and eccentricities of behavior, usually beginning by early adulthood but 
in 
some cases first 
becoming apparent 
in childhood and adolescence. Abnormalities of beliefs, 
thinking, and perception are below the threshold for the diagnosis of a psychotic disorder. 


Two conditions are defined by abnormalities limited to one domain of psychosis: 
delusions 
or catatonia. Delusional 
disorder is characterized by at 
least 
1 month of delusions but 
no other 
psychotic symptoms. Catatonia is described later in the chapter and further in this discussion. 


Brief psychotic disorder lasts more than 1 day and remits by 1 month. Schizophreniform 
disorder is characterized by a symptomatic presentation equivalent 
to that 
of schizophrenia 
except 
for its duration (less than 6 months) and the absence of a requirement 
for a decline in 



functioning. 


Schizophrenia lasts for at 
least 
6 months and includes at 
least 
1 month of active-phase 
symptoms. In schizoaffective disorder, a mood episode and the active-phase symptoms of 
schizophrenia occur together and were preceded or are followed by at 
least 
2 weeks of delusions 
or hallucinations without prominent mood symptoms. 


Psychotic disorders may be induced by substances, medications, toxins, and other medical 
conditions. In substance/medication-induced psychotic disorder, the psychotic symptoms are 
judged to be a direct 
physiological 
consequence of a drug of abuse, a medication, or toxin 
exposure and cease after removal 
of the agent. In psychotic disorder due to another medical 
condition, the psychotic symptoms are judged to be a direct 
physiological 
consequence of 
another medical condition. 


Catatonia can occur in several 
disorders, including neurodevelopmental, psychotic, bipolar, 
depressive, and other mental 
disorders. This chapter also includes the diagnoses catatonia 
associated with another mental 
disorder (catatonia specifier), catatonic disorder due to another 
medical 
condition, and unspecified catatonia, and the diagnostic criteria for all 
three conditions 
are described together. 


Other specified and unspecified schizophrenia spectrum 
and other psychotic disorders are 
included for classifying psychotic presentations that 
do not 
meet 
the criteria for any of the 
specific psychotic disorders, or psychotic symptomatology about 
which there is inadequate or 
contradictory information. 


104 


Clinician-Rated Assessment 
of 
Symptoms and Related Clinical 
Phenomena in Psychosis 


Psychotic disorders are heterogeneous, and the severity of symptoms can predict 
important 
aspects of the illness, such as the degree of cognitive or neurobiological 
deficits. To move the 
field forward, a detailed framework for the assessment 
of severity is included in Section III, 
 Assessment 
Measures,  which may help with treatment 
planning, prognostic decision-making, 
and research on pathophysiological 
mechanisms. Section III,  Assessment 
Measures,  also 
contains dimensional 
assessments of the primary symptoms of psychosis, including 
hallucinations, delusions, disorganized speech (except 
for substance/medication-induced 
psychotic disorder and psychotic disorder due to another medical 
condition), abnormal 
psychomotor behavior, and negative symptoms, as well 
as dimensional 
assessments of 
depression and mania. The severity of mood symptoms in psychosis has prognostic value and 
guides treatment. Thus, dimensional 
assessments of depression and mania for all 
psychotic 
disorders alert 
clinicians to mood pathology and the need to treat 
where appropriate. The Section 
III scale also includes a dimensional 
assessment 
of cognitive impairment. Many individuals with 
psychotic disorders have impairments in a range of cognitive domains that 
predict 
functional 
status. Clinical 
neuropsychological 
assessment 
can help guide diagnosis and treatment, but 
brief 
assessments without 
formal 
neuropsychological 
assessment 
can provide useful 
information that 
can be sufficient 
for diagnostic purposes. Formal 
neuropsychological 
testing, when conducted, 
should be administered and scored by personnel 
trained in the use of testing instruments. If a 



formal 
neuropsychological 
assessment 
is not 
conducted, the clinician should use the best 
available information to make a judgment. Further research on these assessments is necessary to 
determine their clinical 
utility; 
thus, the assessments available in Section III should serve as a 
prototype to stimulate such research. 


Cultural 
Considerations in the Assessment of Psychotic Symptoms 


Diagnostic accuracy and the quality of treatment 
planning may be enhanced by interview 
approaches, scales, and tools that 
have been adapted or validated for the person s culture and by 
using a cultural 
formulation interview (see Section III,  Culture and Psychiatric Diagnosis ). 
Assessing psychosis through interpreters or in a second or third language must 
avoid the 
misunderstanding of unfamiliar metaphors as delusions. 


Schizotypal 
(Personality) Disorder 


Criteria and text 
for schizotypal 
personality disorder can be found in the chapter  Personality 
Disorders.  Because this disorder is considered part 
of the schizophrenia spectrum 
of disorders, 
and is labeled in this section of ICD-10 as schizotypal 
disorder, it 
is listed in this chapter and 
discussed in detail in the DSM-5 chapter  Personality Disorders.  


Delusional 
Disorder 


Diagnostic Criteria 
F22 


A. 
The 
presence 
of 
one 
(or more) delusions with 
a 
duration 
of 
1 
month 
or longer. 
B. 
Criterion 
A 
for schizophrenia 
has never been 
met. 
Note: 
Hallucinations, 
if 
present, 
are 
not 
prominent 
and 
are 
related 
to 
the 
delusional theme 
(e.g., 
the 
sensation 
of 
being 
infested 
with 
insects associated 
with 
delusions of 
infestation). 


105 


C. 
Apart 
from the 
impact 
of 
the 
delusion(s) or its ramifications, 
functioning 
is not 
markedly impaired, 
and 
behavior is not 
obviously bizarre 
or odd. 
D. 
If 
manic or major depressive 
episodes have 
occurred, 
these 
have 
been 
brief 
relative 
to 
the 
duration 
of 
the 
delusional periods. 
E. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
or 
another medical condition 
and 
is not 
better explained 
by another mental 
disorder, 
such 
as body dysmorphic disorder or obsessive-compulsive 
disorder. 
Specify 
whether: 
Erotomanic 
type: 
This subtype 
applies when 
the 
central theme 
of 
the 
delusion 
is that 
another person 
is in 
love 
with 
the 
individual. 



Grandiose 
type: 
This subtype 
applies when 
the 
central theme 
of 
the 
delusion 
is 
the 
conviction 
of 
having 
some 
great 
(but 
unrecognized) talent 
or insight 
or having 
made 
some 
important 
discovery. 


Jealous 
type: 
This subtype 
applies when 
the 
central theme 
of 
the 
individual s 


delusion 
is that 
his or her spouse 
or lover is unfaithful. 
Persecutory 
type: 
This subtype 
applies when 
the 
central theme 
of 
the 
delusion 
involves the 
individual s belief 
that 
he 
or she 
is being 
conspired 
against, 
cheated, 
spied 
on, 
followed, 
poisoned 
or drugged, 
maliciously maligned, 
harassed, 
or 
obstructed 
in 
the 
pursuit 
of 
long-term goals. 


Somatic 
type: 
This subtype 
applies when 
the 
central theme 
of 
the 
delusion 
involves bodily functions or sensations. 


Mixed 
type: 
This subtype 
applies when 
no 
one 
delusional theme 
predominates. 
Unspecified 
type: 
This subtype 
applies when 
the 
dominant 
delusional belief 
cannot 
be 
clearly determined 
or is not 
described 
in 
the 
specific types (e.g., 
referential delusions without 
a 
prominent 
persecutory or grandiose 
component). 


Specify 
if: 
With 
bizarre 
content: 
Delusions are 
deemed 
bizarre 
if 
they are 
clearly 
implausible, 
not 
understandable, 
and 
not 
derived 
from ordinary life 
experiences 
(e.g., 
an 
individual s belief 
that 
a 
stranger has removed 
his or her internal organs 
and 
replaced 
them with 
someone 
else s organs without 
leaving 
any wounds or 


scars). 
Specify 
if: 
The 
following 
course 
specifiers are 
only to 
be 
used 
after a 
1-year duration 
of 
the 


disorder: 
First episode, 
currently 
in 
acute 
episode: 
First 
manifestation 
of 
the 
disorder 


meeting 
the 
defining 
diagnostic symptom and 
time 
criteria. 
An 
acute 
episode 
is a 
time 
period 
in 
which 
the 
symptom criteria 
are 
fulfilled. 
First episode, 
currently 
in 
partial 
remission: 
Partial remission 
is a 
time 
period 


during 
which 
an 
improvement 
after a 
previous episode 
is maintained 
and 
in 


which 
the 
defining 
criteria 
of 
the 
disorder are 
only partially fulfilled. 
First episode, 
currently 
in 
full 
remission: 
Full remission 
is a 
period 
of 
time 
after a 
previous episode 
during 
which 
no 
disorder-specific symptoms are 
present. 


Multiple 
episodes, 
currently 
in 
acute 
episode 
Multiple 
episodes, 
currently 
in 
partial 
remission 
Multiple 
episodes, 
currently 
in 
full 
remission 
Continuous: 
Symptoms fulfilling 
the 
diagnostic symptom criteria 
of 
the 
disorder 


are 
remaining 
for the 
majority of 
the 
illness course, 
with 
subthreshold 
symptom 
periods being 
very brief 
relative 
to 
the 
overall course. 


Unspecified 



Specify 
current 
severity: 
Severity is rated 
by a 
quantitative 
assessment 
of 
the 
primary symptoms of 
psychosis, 
including 
delusions, 
hallucinations, 
disorganized 
speech, 
abnormal 
psychomotor 


106 


behavior, 
and 
negative 
symptoms. 
Each 
of 
these 
symptoms may be 
rated 
for its 
current 
severity (most 
severe 
in 
the 
last 
7 
days) on 
a 
5-point 
scale 
ranging 
from 
0 
(not 
present) to 
4 
(present 
and 
severe). 
(See 
Clinician-Rated 
Dimensions of 
Psychosis Symptom Severity in 
the 
chapter  Assessment 
Measures. ) 


Note: 
Diagnosis of 
delusional disorder can 
be 
made 
without 
using 
this severity 
specifier. 


Subtypes 


In erotomanic type, 
the central 
theme of the delusion is that 
another person is in love with the 
individual. The person about 
whom 
this conviction is held is usually of higher status (e.g., a 
famous individual 
or a superior at 
work) but 
can be a complete stranger. Efforts to contact 
the 
object 
of the delusion are common. In grandiose type, 
the central 
theme of the delusion is the 
conviction of having some great 
talent 
or insight 
or of having made some important 
discovery. 
Less commonly, the individual 
may have the delusion of having a special 
relationship with a 
prominent 
individual 
or of being a prominent 
person (in which case the actual 
individual 
may be 
regarded as an impostor). Grandiose delusions may have a religious content. In jealous type, 
the 
central 
theme of the delusion is that 
of an unfaithful 
partner. This belief is arrived at 
without 
due 
cause and is based on incorrect 
inferences supported by small 
bits of  evidence  (e.g., disarrayed 
clothing). The individual 
with the delusion usually confronts the spouse or lover and attempts to 
intervene in the imagined infidelity. In persecutory type, 
the central 
theme of the delusion 
involves the individual s belief of being conspired against, cheated, spied on, followed, 
poisoned, maliciously maligned, harassed, or obstructed in the pursuit 
of long-term 
goals. Small 
slights may be exaggerated and become the focus of a delusional 
system. The affected individual 
may engage in repeated attempts to obtain satisfaction by legal 
or legislative action. Individuals 
with persecutory delusions are often resentful 
and angry and may resort 
to violence against 
those 
they believe are hurting them. In somatic type, 
the central 
theme of the delusion involves bodily 
functions or sensations. Somatic delusions can occur in several forms. Most common is the belief 
that 
the individual 
emits a foul 
odor; 
that 
there is an infestation of insects on or in the skin; 
that 
there is an internal parasite; or that parts of the body are not functioning. 


Diagnostic Features 


The essential 
feature of delusional 
disorder is the presence of one or more delusions that 
persist 
for at 
least 
1 month (Criterion A). A diagnosis of delusional 
disorder is not 
given if the 
individual 
has ever had a symptom 
presentation that 
met 
Criterion A for schizophrenia (Criterion 
B). Apart 
from 
the direct 
impact 
of the delusions, impairments in psychosocial 
functioning may 
be more circumscribed than those seen in other psychotic disorders such as schizophrenia, and 
behavior is not 
obviously bizarre or odd (Criterion C). If mood episodes occur concurrently with 



the delusions, the total 
duration of these mood episodes is brief relative to the total 
duration of 
the delusional 
periods (Criterion D). The delusions are not 
attributable to the physiological 
effects of a substance (e.g., cocaine) or another medical 
condition (e.g., Alzheimer s disease) and 
are not 
better explained by another mental 
disorder, such as body dysmorphic disorder or 
obsessive-compulsive disorder (Criterion E). 


In addition to the delusions identified in the diagnostic criteria, the assessment 
of cognition, 
depression, and mania symptom 
domains is vital 
for making critically important 
distinctions 
between the various schizophrenia spectrum 
and other psychotic disorders. Whereas delusions 
are a sine qua non of delusional 
disorder, hallucinations and negative symptoms are uncommon 
and disorganization is rare. By definition, the presence of catatonia in conjunction with delusions 
rules out 
delusional 
disorder, because Criterion A for schizophrenia would be met. A subset 
of 
cases has prominent 
depressive symptoms, but 
cognitive impairment 
and mania are rarely 
demonstrated. 


107 


Associated Features 


Social, marital, or work problems can result 
from 
the delusional 
beliefs of delusional 
disorder. 
Individuals with delusional 
disorder may be able to factually describe that 
others view their 
beliefs as irrational 
but 
are unable to accept 
this themselves (i.e., there may be  factual 
insight  
but 
no true insight). Many individuals develop irritable or dysphoric mood, which can sometimes 
be understood as a reaction to their delusional 
beliefs. Anger and violent 
behavior can occur with 
persecutory, jealous, and erotomanic types. The individual 
may engage in litigious or 
antagonistic behavior (e.g., sending hundreds of letters of protest 
to the government). Legal 
difficulties can occur, particularly in jealous and erotomanic types. 


Prevalence 


The lifetime prevalence of delusional 
disorder has been estimated at 
around 0.2% in a Finnish 
sample, and the most 
frequent 
subtype is persecutory. Delusional 
disorder, jealous type, is 
probably more common in men than in women, but 
there are no major sex or gender differences 
in the overall frequency of delusional disorder or in the content of the delusions. 


Development and Course 


On average, global 
functioning is generally better than that 
observed in schizophrenia. Although 
the diagnosis is generally stable, a proportion of individuals go on to develop schizophrenia. 
Whereas about 
a third of individuals with delusional 
disorder of 1 3 months  duration 
subsequently receive a diagnosis of schizophrenia, the diagnosis of delusional 
disorder is much 
less likely to change if the duration of the disorder is greater than 6 12 months. Although 
delusional 
disorder can occur in younger age groups, it 
may be more prevalent 
in older 
individuals. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Delusional 
disorder has a significant 
familial 
relationship with both 
schizophrenia and schizotypal personality disorder. 



Culture-Related Diagnostic Issues 


An individual s cultural 
and religious background must 
be taken into account 
in evaluating the 
possible presence of delusional 
disorder; 
in fact, some traditional 
beliefs unfamiliar to Western 
cultures may be wrongly labeled as delusional, so their context 
must 
be carefully assessed. The 
nature and content of delusions also vary among different cultural groups. 


Functional 
Consequences of Delusional 
Disorder 


The functional 
impairment 
is usually more circumscribed than that 
seen with other psychotic 
disorders, although in some cases, the impairment 
may be substantial 
and include poor 
occupational 
functioning and social 
isolation. When poor psychosocial 
functioning is present, 
delusional 
beliefs themselves often play a significant 
role. A common characteristic of 
individuals with delusional 
disorder is the apparent 
normality of their behavior and appearance 
when their delusional 
ideas are not 
being discussed or acted on. Men with delusional 
disorder 
generally have more severe symptoms and worse functional outcomes compared with women. 


Differential 
Diagnosis 


Obsessive-compulsive 
and 
related 
disorders. 
If an individual 
with obsessive-compulsive disorder is 
completely convinced that 
his or her obsessive-compulsive disorder beliefs are true, then the 
diagnosis of obsessive-compulsive disorder, with absent insight/delusional 


108 


beliefs specifier, should be given rather than a diagnosis of delusional 
disorder. Similarly, if an 
individual 
with body dysmorphic disorder is completely convinced that 
his or her body 
dysmorphic disorder beliefs are true, then the diagnosis of body dysmorphic disorder, with 
absent 
insight/delusional 
beliefs specifier, should be given rather than a diagnosis of delusional 
disorder. 


Delirium, 
major neurocognitive 
disorder, 
and 
psychotic 
disorder due 
to 
another medical 
condition. 


Individuals with these disorders may present 
with symptoms that 
suggest 
delusional 
disorder. 
For example, simple persecutory delusions in the context 
of major neurocognitive disorder 
would be diagnosed as major neurocognitive disorder, with behavioral disturbance. 
Substance/medication-induced 
psychotic 
disorder. 
A substance/medication-induced psychotic 


disorder cross-sectionally may be identical 
in symptomatology to delusional 
disorder but 
can be 
distinguished by the chronological 
relationship of substance use to the onset 
and remission of the 
delusional beliefs. 


Schizophrenia 
and 
schizophreniform disorder. 
Delusional 
disorder can be distinguished from 
schizophrenia and schizophreniform 
disorder by the absence of the other characteristic 
symptoms of the active phase of schizophrenia. Furthermore, the quality of delusions can help 
distinguish between schizophrenia and delusional 
disorder. In schizophrenia, delusions show 
greater disorganization (the degree to which delusions are internally consistent, logical, and 
systematized), whereas in delusional 
disorder, they show greater conviction (the degree to which 
the individual 
is convinced of the reality of the delusion), greater extension (the degree to which 
the delusion involves various areas of the individual s life), and greater pressure (the degree to 



which the individual is preoccupied and concerned with the expressed delusion). 


Depressive 
and 
bipolar disorders 
and 
schizoaffective 
disorder. 
These disorders may be distinguished 
from 
delusional 
disorder by the temporal 
relationship between the mood disturbance and the 
delusions and by the severity of the mood symptoms. If delusions occur exclusively during mood 
episodes, the diagnosis is major depressive or bipolar disorder, with psychotic features. Mood 
symptoms that 
meet 
full 
criteria for a mood episode can be superimposed on delusional 
disorder. 
Delusional 
disorder can be diagnosed only if the total 
duration of all 
mood episodes remains 
brief relative to the total 
duration of the delusional 
disturbance. If not, then a diagnosis of other 
specified or unspecified schizophrenia spectrum 
and other psychotic disorder accompanied by 
other specified depressive disorder, unspecified depressive disorder, other specified bipolar and 
related disorder, or unspecified bipolar and related disorder is appropriate. 


Brief Psychotic Disorder 


Diagnostic Criteria 
F23 


A. 
Presence 
of 
one 
(or more) of 
the 
following 
symptoms. 
At 
least 
one 
of 
these 
must 
be 
(1), 
(2), 
or (3): 
1. 
Delusions. 
2. 
Hallucinations. 
3. 
Disorganized 
speech 
(e.g., 
frequent 
derailment 
or incoherence). 
4. 
Grossly disorganized 
or catatonic behavior. 
Note: 
Do 
not 
include 
a 
symptom if 
it 
is a 
culturally sanctioned 
response. 
B. 
Duration 
of 
an 
episode 
of 
the 
disturbance 
is at 
least 
1 
day but 
less than 
1 
month, 
with 
eventual full return 
to 
premorbid 
level of 
functioning. 
109 


C. 
The 
disturbance 
is not 
better explained 
by major depressive 
or bipolar disorder 
with 
psychotic features or another psychotic disorder such 
as schizophrenia 
or 
catatonia, 
and 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition. 
Specify 
if: 
With 
marked 
stressor(s) 
(brief 
reactive 
psychosis): 
If 
symptoms occur in 


response 
to 
events that, 
singly or together, 
would 
be 
markedly stressful to 
almost 
anyone 
in 
similar circumstances in 
the 
individual s culture. 
Without marked 
stressor(s): 
If 
symptoms do 
not 
occur in response 
to 
events 


that, 
singly or together, 
would 
be 
markedly stressful to 
almost 
anyone 
in 
similar 
circumstances in 
the 
individual s culture. 
With 
peripartum onset: 
If 
onset 
is during 
pregnancy or within 
4 
weeks 



postpartum. 
Specify 
if: 
With 
catatonia 
(refer to 
the 
criteria 
for catatonia 
associated 
with 
another mental 
disorder, 
p. 
135, 
for definition). 
Coding 
note: 
Use 
additional code 
F06.1 
catatonia 
associated 
with 
brief 
psychotic disorder to 
indicate 
the 
presence 
of 
the 
comorbid 
catatonia. 
Specify 
current 
severity: 
Severity is rated 
by a 
quantitative 
assessment 
of 
the 
primary symptoms of 
psychosis, 
including 
delusions, 
hallucinations, 
disorganized 
speech, 
abnormal 
psychomotor behavior, 
and 
negative 
symptoms. 
Each 
of these 
symptoms may 
be 
rated 
for its current 
severity (most 
severe 
in 
the 
last 7 
days) on 
a 
5-point 
scale 
ranging 
from 0 
(not 
present) to 
4 
(present 
and 
severe). 
(See 
Clinician-

Rated 
Dimensions of 
Psychosis Symptom Severity in 
the 
chapter  Assessment 
Measures. ) 
Note: 
Diagnosis of 
brief 
psychotic disorder can 
be 
made 
without 
using 
this 


severity specifier. 


Diagnostic Features 


The essential 
feature of brief psychotic disorder is a disturbance that 
involves at 
least 
one of the 
following positive psychotic symptoms: 
delusions, hallucinations, disorganized speech (e.g., 
frequent 
derailment 
or incoherence), or grossly abnormal 
psychomotor behavior, including 
catatonia (Criterion A). An episode of the disturbance lasts at 
least 
1 day but 
less than 1 month, 
and the individual 
eventually has a full 
return to the premorbid level 
of functioning (Criterion B). 
The disturbance is not 
better explained by a depressive or bipolar disorder with psychotic 
features, by schizoaffective disorder, or by schizophrenia and is not 
attributable to the 
physiological 
effects of a substance (e.g., a hallucinogen) or another medical 
condition (e.g., 
subdural hematoma) (Criterion C). 


In addition to the four symptom 
domain areas identified in the diagnostic criteria, the 
assessment 
of cognition, depression, and mania symptom 
domains is vital 
for making critically 
important distinctions between the various schizophrenia spectrum and other psychotic disorders. 


Associated Features 


Individuals with brief psychotic disorder typically experience emotional 
turmoil 
or 
overwhelming confusion. They may have rapid shifts from 
one intense affect 
to another. 
Although the disturbance is brief, the level 
of impairment 
may be severe, and supervision may be 
required to ensure that 
nutritional 
and hygienic needs are met 
and that 
the individual 
is protected 
from 
the consequences of poor judgment, cognitive impairment, or acting on the basis of 
delusions. There appears to be an increased risk of suicidal 
behavior, particularly during the 
acute episode. 


110 


Prevalence 



Brief psychotic disorder may account 
for 2% 7% of cases of first-onset 
psychosis in several 
countries. 


Development and Course 


Brief psychotic disorder may appear in adolescence or early adulthood, and onset 
can occur 
across the life span, with the average age at 
onset 
being the mid 30s. By definition, a diagnosis of 
brief psychotic disorder requires a full 
remission of all 
symptoms and an eventual 
full 
return to 
the premorbid level 
of functioning within 1 month of the onset 
of the disturbance. In some 
individuals, the duration of psychotic symptoms may be quite brief (e.g., a few days). 


Although brief psychotic disorder by definition reaches a full 
remission within 1 month, 
subsequently more than 50% of the individuals experience a relapse. Despite the possibility of 
relapse, for most 
individuals, outcome is favorable in terms of social 
functioning and 
symptomatology. 


In less than half of cases diagnosed with DSM-IV brief psychotic disorder or ICD-10 acute 
and transient 
psychotic disorder, the diagnosis changes more often to schizophrenia spectrum 
disorders and less often to affective disorders or to other psychotic disorders. 


Culture-Related Diagnostic Issues 


It 
is important 
to distinguish symptoms of brief psychotic disorder from 
culturally sanctioned 
response patterns. For example, in some religious ceremonies, an individual 
may report 
hearing 
voices, but 
these do not 
generally persist 
and are not 
perceived as abnormal 
by most 
members of 
the individual s community. In a wide range of cultural 
contexts, it 
would be common or 
expected for bereaved relatives to hear, see, or interact 
with the spirit 
of a recently deceased 
loved one without 
notable pathological 
sequelae. In addition, cultural 
and religious background 
must be taken into account when considering whether beliefs are delusional. 


Differential 
Diagnosis 


Other medical 
conditions. 
A variety of medical 
conditions can manifest 
with psychotic symptoms 
of short 
duration. Psychotic disorder due to another medical 
condition or a delirium 
is diagnosed 
when there is evidence from 
the history, physical 
examination, or laboratory tests that 
the 
delusions or hallucinations are the direct 
physiological 
consequence of a specific medical 
condition (e.g., Cushing s syndrome, brain tumor) (see  Psychotic Disorder Due to Another 
Medical Condition  later in this chapter). 


Substance-related 
disorders. 
Substance/medication-induced psychotic disorder, substance-induced 
delirium, and substance intoxication are distinguished from 
brief psychotic disorder by the fact 
that 
a substance (e.g., a drug of abuse, a medication, exposure to a toxin) is judged to be 
etiologically related to the psychotic symptoms (see  Substance/Medication-Induced Psychotic 
Disorder  later in this chapter). Laboratory tests, such as a urine drug screen or a blood alcohol 
level, may be helpful 
in making this determination, as may a careful 
history of substance use 
with attention to temporal 
relationships between substance intake and onset 
of the symptoms and 
to the nature of the substance being used. 


Depressive 
and 
bipolar disorders. 
The diagnosis of brief psychotic disorder cannot 
be made if the 
psychotic symptoms are better explained by a mood episode (i.e., the psychotic symptoms occur 
exclusively during a full major depressive, manic, or mixed episode). 



Other psychotic 
disorders. 
If the psychotic symptoms persist 
for 1 month or longer, the diagnosis 
is either schizophreniform 
disorder, delusional 
disorder, depressive disorder with psychotic 
features, bipolar disorder with psychotic features, or other specified or 


111 


unspecified schizophrenia spectrum 
and other psychotic disorder, depending on the other 
symptoms in the presentation. The differential 
diagnosis between brief psychotic disorder and 
schizophreniform 
disorder is difficult 
when the psychotic symptoms have remitted before 1 
month in response to successful 
treatment 
with medication. Careful 
attention should be given to 
the possibility that 
a recurrent 
disorder (e.g., bipolar disorder, recurrent 
acute exacerbations of 
schizophrenia) may be responsible for any recurring psychotic episodes. 


Malingering 
and 
factitious 
disorders. 
An episode of factitious disorder with predominantly 
psychological 
signs and symptoms may have the appearance of brief psychotic disorder, but 
in 
such cases there is evidence that 
the symptoms are intentionally produced. When malingering 
involves apparently psychotic symptoms, there is usually evidence that 
the illness is being 
feigned for an understandable goal. 


Personality 
disorders. 
In certain individuals with personality disorders, psychosocial 
stressors 
may precipitate brief periods of psychotic symptoms. These symptoms are usually transient 
and 
do not 
warrant 
a separate diagnosis. If psychotic symptoms persist 
for at 
least 
1 day, an 
additional diagnosis of brief psychotic disorder may be appropriate. 


Schizophreniform Disorder 


Diagnostic Criteria 
F20.81 


A. 
Two 
(or more) of 
the 
following, 
each 
present 
for a 
significant 
portion 
of 
time 
during 
a 
1-month 
period 
(or less if 
successfully treated). 
At 
least 
one 
of 
these 
must 
be 
(1), 
(2), 
or (3): 
1. 
Delusions. 
2. 
Hallucinations. 
3. 
Disorganized 
speech 
(e.g., 
frequent 
derailment 
or incoherence). 
4. 
Grossly disorganized 
or catatonic behavior. 
5. 
Negative 
symptoms (i.e., 
diminished 
emotional expression 
or avolition). 
B. 
An 
episode 
of 
the 
disorder lasts at 
least 
1 
month 
but 
less than 
6 
months. 
When 
the 
diagnosis must 
be 
made 
without 
waiting 
for recovery, 
it 
should 
be 
qualified 
as  provisional.  
C. 
Schizoaffective 
disorder and 
depressive 
or bipolar disorder with 
psychotic 
features have 
been 
ruled 
out 
because 
either 1) no 
major depressive 
or manic 
episodes have 
occurred 
concurrently with 
the 
active-phase 
symptoms, 
or 2) if 
mood 
episodes have 
occurred 
during 
active-phase 
symptoms, 
they have 
been 

present 
for a 
minority of 
the 
total duration 
of 
the 
active 
and 
residual periods of 
the 
illness. 


D. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition. 
Specify 
if: 
With 
good 
prognostic 
features: 
This specifier requires the 
presence 
of 
at 
least 
two 
of 
the 
following 
features: 
onset 
of 
prominent 
psychotic symptoms within 
4 
weeks of 
the 
first 
noticeable 
change 
in 
usual behavior or functioning; 
confusion 
or perplexity; 
good 
premorbid 
social and 
occupational functioning; 
and 
absence 
of 
blunted 
or flat 
affect. 


Without good 
prognostic 
features: 
This specifier is applied 
if 
two 
or more 
of 
the 
above 
features have 
not 
been 
present. 


Specify 
if: 
With 
catatonia 
(refer to 
the 
criteria 
for catatonia 
associated 
with 
another mental 
disorder, 
p. 
135, 
for definition). 


112 


Coding 
note: 
Use 
additional code 
F06.1 
catatonia 
associated 
with 
schizophreniform disorder to 
indicate 
the 
presence 
of 
the 
comorbid 
catatonia. 


Specify 
current 
severity: 
Severity is rated 
by a 
quantitative 
assessment 
of 
the 
primary symptoms of 
psychosis, 
including 
delusions, 
hallucinations, 
disorganized 
speech, 
abnormal 
psychomotor behavior, 
and 
negative 
symptoms. 
Each 
of these 
symptoms may 
be 
rated 
for its current 
severity (most 
severe 
in 
the 
last 7 
days) on 
a 
5-point 
scale 
ranging 
from 0 
(not 
present) to 
4 
(present 
and 
severe). 
(See 
Clinician-
Rated 
Dimensions of 
Psychosis Symptom Severity in 
the 
chapter  Assessment 
Measures. ) 


Note: 
Diagnosis of 
schizophreniform disorder can 
be 
made 
without 
using 
this 
severity specifier. 


Note: 
For additional information 
on 
Associated 
Features, 
Development 
and 
Course 
(age-related 
factors), 
Culture-Related 
Diagnostic Issues, 
Sex- and 
Gender-Related 
Diagnostic Issues, 
Differential Diagnosis, 
and 
Comorbidity, 
see 
the 
corresponding 
sections in 
Schizophrenia. 


Diagnostic Features 


The characteristic symptoms of schizophreniform 
disorder are identical 
to those of schizophrenia 
(Criterion A). Schizophreniform 
disorder is distinguished by its difference in duration: 
the total 
duration of the illness, including prodromal, active, and residual 
phases, is at 
least 
1 month but 
less than 6 months (Criterion B). The duration requirement 
for schizophreniform 
disorder is 
intermediate between that 
for brief psychotic disorder, which lasts more than 1 day and remits by 
1 month, and schizophrenia, which lasts for at 
least 
6 months. The diagnosis of schizophreniform 



disorder is made under two conditions: 
1) when an episode of illness lasts between 1 and 6 
months and the individual 
has already recovered, and 2) when an individual 
is symptomatic for 
less than the 6 months  duration required for the diagnosis of schizophrenia but 
has not 
yet 
recovered. In this case, the diagnosis should be noted as  schizophreniform 
disorder 
(provisional)  because it 
is uncertain if the individual 
will 
recover from 
the disturbance within 
the 6-month period. If the disturbance persists beyond 6 months, the diagnosis should be changed 
to schizophrenia. 


Another distinguishing feature of schizophreniform 
disorder is the lack of a criterion 
requiring impaired social 
and occupational 
functioning. While such impairments may potentially 
be present, they are not necessary for a diagnosis of schizophreniform disorder. 


In addition to the five symptom 
domain areas identified in the diagnostic criteria, the 
assessment 
of cognition, depression, and mania symptom 
domains is vital 
for making critically 
important distinctions between the various schizophrenia spectrum and other psychotic disorders. 


Associated Features 


As with schizophrenia, currently there are no laboratory or psychometric tests for 
schizophreniform 
disorder. There are multiple brain regions where neuroimaging, 
neuropathological, and neurophysiological 
research has indicated abnormalities, but 
none are 
diagnostic. 


Prevalence 


Incidence of schizophreniform 
disorder across sociocultural 
settings is likely similar to that 
observed in schizophrenia. In the United States and other high-income countries, the incidence is 
low, possibly fivefold less than that 
of schizophrenia. In lower-income countries, the incidence 
may be higher, especially for the specifier  with good prognostic features ; 
in some of these 
settings schizophreniform disorder may be as common as schizophrenia. 


113 


Development and Course 


The development 
of schizophreniform 
disorder is similar to that 
of schizophrenia. About 
one-
third of individuals with an initial 
diagnosis of schizophreniform 
disorder (provisional) recover 
within the 6-month period and schizophreniform 
disorder is their final 
diagnosis. The majority of 
the remaining two-thirds of individuals will 
eventually receive a diagnosis of schizophrenia or 
schizoaffective disorder. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Relatives of individuals with schizophreniform 
disorder have an 
increased risk for schizophrenia. 


Functional 
Consequences of Schizophreniform Disorder 


For the majority of individuals with schizophreniform 
disorder who eventually receive a 
diagnosis of schizophrenia or schizoaffective disorder, the functional 
consequences are similar to 
the consequences of those disorders. Most 
individuals experience dysfunction in several 
areas of 



daily functioning, such as school 
or work, interpersonal 
relationships, and self-care. Individuals 
who recover from schizophreniform disorder have better functional outcomes. 


Differential 
Diagnosis 


Other mental 
disorders 
and 
medical 
conditions. 
A wide variety of mental 
disorders and medical 
conditions can manifest 
with psychotic symptoms that 
must 
be considered in the differential 
diagnosis of schizophreniform 
disorder. These include psychotic disorder due to another medical 
condition or its treatment; 
delirium 
or major neurocognitive disorder; 
substance/medicationinduced 
psychotic disorder or delirium; 
major depressive or bipolar disorder with psychotic 
features; 
schizoaffective disorder; 
other specified or unspecified bipolar and related disorder; 
major depressive or bipolar disorder with catatonic features; 
schizophrenia; 
delusional 
disorder; 
other specified or unspecified schizophrenia spectrum 
and other psychotic disorder; 
schizotypal, 
schizoid, or paranoid personality disorders; 
autism 
spectrum 
disorder; 
disorders presenting in 
childhood with disorganized speech; 
attention-deficit/hyperactivity disorder; 
obsessive-
compulsive disorder; posttraumatic stress disorder; and traumatic brain injury. 


Since the diagnostic criteria for schizophreniform 
disorder and schizophrenia differ primarily 
in duration of illness, the discussion of the differential 
diagnosis of schizophrenia also applies to 
schizophreniform disorder. 
Brief 
psychotic 
disorder. 
Schizophreniform 
disorder differs in duration from 
brief psychotic 


disorder, which has a duration of less than 1 month. 


Schizophrenia 


Diagnostic Criteria 
F20.9 


A. 
Two 
(or more) of 
the 
following, 
each 
present 
for a 
significant 
portion 
of 
time 
during 
a 
1-month 
period 
(or less if 
successfully treated). 
At 
least 
one 
of 
these 
must 
be 
(1), 
(2), 
or (3): 
1. 
Delusions. 
2. 
Hallucinations. 
3. 
Disorganized 
speech 
(e.g., 
frequent 
derailment 
or incoherence). 
114 


4. 
Grossly disorganized 
or catatonic behavior. 
5. 
Negative 
symptoms (i.e., 
diminished 
emotional expression 
or avolition). 
B. 
For a 
significant 
portion 
of 
the 
time 
since 
the 
onset 
of 
the 
disturbance, 
level of 
functioning 
in 
one 
or more 
major areas, 
such 
as work, 
interpersonal relations, 
or 
self-care, 
is markedly below the 
level achieved 
prior to 
the 
onset 
(or when 
the 
onset 
is in 
childhood 
or adolescence, 
there 
is failure 
to 
achieve 
expected 
level of 
interpersonal, 
academic, 
or occupational functioning). 

C. 
Continuous signs of 
the 
disturbance 
persist 
for at 
least 
6 
months. 
This 6-month 
period 
must 
include 
at 
least 
1 
month 
of 
symptoms (or less if 
successfully treated) 
that 
meet 
Criterion 
A 
(i.e., 
active-phase 
symptoms) and 
may include 
periods of 
prodromal or residual symptoms. 
During 
these 
prodromal or residual periods, 
the 
signs of 
the 
disturbance 
may be 
manifested 
by only negative 
symptoms or by 
two 
or more 
symptoms listed 
in 
Criterion 
A 
present 
in 
an 
attenuated 
form (e.g., 
odd 
beliefs, 
unusual perceptual experiences). 
D. 
Schizoaffective 
disorder and 
depressive 
or bipolar disorder with 
psychotic 
features have 
been 
ruled 
out 
because 
either 1) no 
major depressive 
or manic 
episodes have 
occurred 
concurrently with 
the 
active-phase 
symptoms, 
or 2) if 
mood 
episodes have 
occurred 
during 
active-phase 
symptoms, 
they have 
been 
present 
for a 
minority of 
the 
total duration 
of 
the 
active 
and 
residual periods of 
the 
illness. 
E. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition. 
F. 
If 
there 
is a 
history of 
autism spectrum disorder or a 
communication 
disorder of 
childhood 
onset, 
the 
additional diagnosis of 
schizophrenia 
is made 
only if 
prominent 
delusions or hallucinations, 
in 
addition 
to 
the 
other required 
symptoms 
of 
schizophrenia, 
are 
also 
present 
for at 
least 
1 
month 
(or less if 
successfully 
treated). 
Specify 
if: 
The 
following 
course 
specifiers are 
only to 
be 
used 
after a 
1-year duration 
of 
the 
disorder and 
if 
they are 
not 
in 
contradiction 
to 
the 
diagnostic course 
criteria. 
First episode, 
currently 
in 
acute 
episode: 
First 
manifestation 
of 
the 
disorder 


meeting 
the 
defining 
diagnostic symptom and 
time 
criteria. 
An 
acute 
episode 
is a 
time 
period 
in 
which 
the 
symptom criteria 
are 
fulfilled. 
First episode, 
currently 
in 
partial 
remission: 
Partial remission 
is a 
period 
of 


time 
during 
which 
an 
improvement 
after a 
previous episode 
is maintained 
and 
in 


which 
the 
defining 
criteria 
of 
the 
disorder are 
only partially fulfilled. 
First episode, 
currently 
in 
full 
remission: 
Full remission 
is a 
period 
of 
time 
after a 
previous episode 
during 
which 
no 
disorder-specific symptoms are 
present. 


Multiple 
episodes, 
currently 
in 
acute 
episode: 
Multiple 
episodes may be 
determined 
after a 
minimum of 
two 
episodes (i.e., 
after a 
first 
episode, 
a 
remission 
and 
a 
minimum of 
one 
relapse). 


Multiple 
episodes, 
currently 
in 
partial 
remission 
Multiple 
episodes, 
currently 
in 
full 
remission 
Continuous: 
Symptoms fulfilling 
the 
diagnostic symptom criteria 
of 
the 
disorder 


are 
remaining 
for the 
majority of 
the 
illness course, 
with 
subthreshold 
symptom 
periods being 
very brief 
relative 
to 
the 
overall course. 


Unspecified 



Specify 
if: 
With 
catatonia 
(refer to 
the 
criteria 
for catatonia 
associated 
with 
another mental 
disorder, 
p. 
135, 
for definition). 
Coding 
note: 
Use 
additional code 
F06.1 
catatonia 
associated 
with 
schizophrenia 
to 
indicate 
the 
presence 
of 
the 
comorbid 
catatonia. 


115 


Specify 
current 
severity: 
Severity is rated 
by a 
quantitative 
assessment 
of 
the 
primary symptoms of 
psychosis, 
including 
delusions, 
hallucinations, 
disorganized 
speech, 
abnormal 
psychomotor behavior, 
and 
negative 
symptoms. 
Each 
of these 
symptoms may 
be 
rated 
for its current 
severity (most 
severe 
in 
the 
last 7 
days) on 
a 
5-point 
scale 
ranging 
from 0 
(not 
present) to 
4 
(present 
and 
severe). 
(See 
Clinician-

Rated 
Dimensions of 
Psychosis Symptom Severity in 
the 
chapter  Assessment 
Measures. ) 
Note: 
Diagnosis of 
schizophrenia 
can 
be 
made 
without 
using 
this severity 


specifier. 


Diagnostic Features 


The characteristic symptoms of schizophrenia involve a range of cognitive, behavioral, and 
emotional 
dysfunctions, but 
no single symptom 
is pathognomonic of the disorder. The diagnosis 
involves the recognition of a constellation of signs and symptoms associated with impaired 
occupational 
or social 
functioning. Individuals with the disorder will 
vary substantially on most 
features, as schizophrenia is a heterogeneous clinical syndrome. 


At 
least 
two Criterion A symptoms must 
be present 
for a significant 
portion of time during a 
1-month period or longer. At 
least 
one of these symptoms must 
be the clear presence of 
delusions (Criterion A1), hallucinations (Criterion A2), or disorganized speech (Criterion A3). 
Grossly disorganized or catatonic behavior (Criterion A4) and negative symptoms (Criterion A5) 
may also be present. In those situations in which the active-phase symptoms remit 
within a 
month in response to treatment, Criterion A is still 
met 
if the clinician estimates that 
they would 
have persisted in the absence of treatment. 


Schizophrenia involves impairment 
in one or more major areas of functioning (Criterion B). 
If the disturbance begins in childhood or adolescence, the expected level 
of function is not 
attained. Comparing the individual 
with unaffected siblings may be helpful. The dysfunction 
persists for a substantial 
period during the course of the disorder and does not 
appear to be a 
direct 
result 
of any single feature. Avolition (i.e., reduced drive to pursue goal-directed behavior; 
Criterion A5) is linked to the social 
dysfunction described under Criterion B. There is also strong 
evidence for a relationship between cognitive impairment 
(see the section  Associated Features  
for this disorder) and functional impairment in individuals with schizophrenia. 


Some signs of the disturbance must 
persist 
for a continuous period of at 
least 
6 months 
(Criterion C). Prodromal 
symptoms often precede the active phase, and residual 
symptoms may 
follow it, characterized by mild or subthreshold forms of hallucinations or delusions. Individuals 



may express a variety of unusual 
or odd beliefs that 
are not 
of delusional 
proportions (e.g., ideas 
of reference or magical 
thinking); 
they may have unusual 
perceptual 
experiences (e.g., sensing 
the presence of an unseen person); 
their speech may be generally understandable but 
vague; 
and 
their behavior may be unusual 
but 
not 
grossly disorganized (e.g., mumbling in public). Negative 
symptoms are common in the prodromal 
and residual 
phases and can be severe. Individuals who 
had been socially active may become withdrawn from 
previous routines. Such behaviors are 
often the first sign of a disorder. 


Mood symptoms and full 
mood episodes are common in schizophrenia and may be 
concurrent 
with active-phase symptomatology. However, as distinct 
from 
a psychotic mood 
disorder, a schizophrenia diagnosis requires the presence of delusions or hallucinations in the 
absence of mood episodes. In addition, mood episodes, taken in 
total, should be present 
for only 
a minority of the total duration of the active and residual periods of the illness. 


In addition to the five symptom 
domain areas identified in the diagnostic criteria, the 
assessment 
of cognition, depression, and mania symptom 
domains is vital 
for making critically 
important distinctions between the various schizophrenia spectrum and other psychotic disorders. 


116 


Associated Features 


Individuals with schizophrenia may display inappropriate affect (e.g., laughing in the absence of 
an appropriate stimulus); 
a dysphoric mood that 
can take the form 
of depression, anxiety, or 
anger; 
a disturbed sleep pattern (e.g., daytime sleeping and nighttime activity); 
and a lack of 
interest 
in eating or food refusal. Depersonalization, derealization, and somatic concerns may 
occur and sometimes reach delusional 
proportions. Anxiety and phobias are common. Cognitive 
deficits in schizophrenia are common and are strongly linked to vocational 
and functional 
impairments. These deficits can include decrements in declarative memory, working memory, 
language function, and other executive functions, as well 
as slower processing speed. 
Abnormalities in sensory processing and inhibitory capacity, as well 
as reductions in attention, 
are also found. Some individuals with schizophrenia show social 
cognition deficits, including 
deficits in the ability to infer the intentions of other people (theory of mind), and may attend to 
and then interpret 
irrelevant 
events or stimuli 
as meaningful, perhaps leading to the generation of 
explanatory delusions. These impairments frequently persist during symptomatic remission. 


Some individuals with psychosis may lack insight 
or awareness of their disorder (i.e., 
anosognosia). This lack of  insight  includes unawareness of symptoms of schizophrenia and 
may be present 
throughout 
the entire course of the illness. Unawareness of illness is typically a 
symptom 
of schizophrenia itself rather than a coping strategy. It 
is comparable to the lack of 
awareness of neurological 
deficits following brain damage, termed anosognosia. 
This symptom 
is the most 
common predictor of nonadherence to treatment, and it 
predicts higher relapse rates, 
increased number of involuntary treatments, poorer psychosocial 
functioning, aggression, and a 
poorer course of illness. 


Hostility and aggression can be associated with schizophrenia, although spontaneous or 
random 
assault 
is uncommon. Aggression is more frequent 
for younger males and for individuals 
with a past 
history of violence, nonadherence to treatment, substance abuse, and impulsivity. It 
should be noted that 
the vast 
majority of persons with schizophrenia are not 
aggressive and are 



more frequently victimized than are individuals in the general population. 


Currently, there are no radiological, laboratory, or psychometric tests for the disorder. 
Differences are evident 
in multiple brain regions between groups of healthy individuals and 
persons with schizophrenia, including evidence from 
neuroimaging, neuropathological, and 
neurophysiological 
studies. Differences are also evident 
in cellular architecture, white matter 
connectivity, and gray matter volume in a variety of regions such as the prefrontal 
and temporal 
cortices. Reduced overall 
brain volume has been observed, as well 
as increased brain volume 
reduction with age. Brain volume reductions with age are more pronounced in individuals with 
schizophrenia than in healthy individuals. Finally, individuals with schizophrenia appear to differ 
from individuals without the disorder in eye-tracking and electrophysiological indices. 


Neurological 
soft 
signs common in individuals with schizophrenia include impairments in 
motor coordination, sensory integration, and motor sequencing of complex movements; 
left-right 
confusion; 
and disinhibition of associated movements. In addition, minor physical 
anomalies of 
the face and limbs may occur. 


Prevalence 


The estimated lifetime prevalence of schizophrenia is approximately 0.3% 0.7%, with variation 
over a fivefold range in meta-analyses of nationally representative surveys. Studies have shown 
increased prevalence and incidence of schizophrenia for some groups based on migration and 
refugee status, urbanicity, and the economic status and latitude of the country. It 
is important 
to 
note that 
the reported prevalence and incidence of schizophrenia may be affected by the fact 
that 
some groups are more likely to be misdiagnosed or overdiagnosed. 


117 


The sex ratio differs across samples and populations: 
for example, presentations with 
prominent 
negative symptoms and longer duration of disorder (associated with poorer outcome) 
show higher incidence rates for men, whereas definitions allowing for the inclusion of more 
mood symptoms and brief presentations (associated with better outcome) show equivalent 
risks 
for both sexes. A large worldwide study, which was based on a range of definitions of 
schizophrenia, found no difference in prevalence between the sexes. 


Development and Course 


The requisite psychotic features of the schizophrenia diagnosis typically emerge between the late 
teens and the mid-30s; 
onset 
prior to adolescence is rare. The peak onset 
age occurs in the early-
to mid-20s for men and in the late-20s for women. The onset 
may be abrupt 
or insidious, but 
the 
majority of individuals manifest 
a slow and gradual 
development 
of a variety of clinically 
significant 
signs and symptoms, particularly social 
withdrawal, emo-tional 
changes, and 
cognitive changes producing a deterioration in role functioning. Half of these individuals display 
depressive symptoms. Prognosis is influenced both by dura-tion and by severity of illness and 
gender. Men, especially those with long duration of psychosis before treatment 
and lower 
premorbid adjustment, have more prominent 
negative symptoms, cognitive impairment, and 
generally worse functional 
outcomes than women. Sociocognitive deficits may manifest 
during 
development 
and precede the emergence of psychosis, taking the form 
of stable impairments 
during adulthood, refractory to antipsychotic medications. 



Course and outcome in schizophrenia are heterogeneous, and prognosis is uncertain at 
the 
onset 
of psychosis. Although most 
individuals with schizophrenia remain vulnerable to 
exacerbation of psychotic symptoms and a chronic course defined by symptoms and functional 
impairment 
is common, many individuals experience periods of remission and even recovery. 
According to a meta-analysis of 79 longitudinal 
studies of first-episode psychosis with more than 
1 year of follow-up, the pooled remission rate (qualitatively defined as mild or absent 
symptoms 
for at 
least 
6 months) for first-episode schizophrenia was 56% and the pooled recovery rate 
(qualitatively defined as symptomatic and functional 
improvement 
for greater than 2 years) was 
30%. A different 
meta-analysis of 50 studies of individuals with broadly defined schizophrenia 
(i.e., schizophrenia, schizophreniform, schizoaffective, or delusional 
disorder) found that 
the 
median proportion of individuals who met 
recovery criteria (at 
most 
mild symptoms and 
improvements in social 
and/or occupational 
functioning persisting for at 
least 
2 years) was 
13.5%. There is a tendency for reduced psychotic experiences during late life. In addition to 
psychosis, cognitive impairment 
and negative symptom 
pathology are core features of 
schizophrenia, and the course for these characteristic features is different 
from 
that 
of positive 
psychotic symptoms. Cognition tends to decline during development 
prior to full 
psychosis and 
is relatively stable over the longer term. Negative symptoms, if present 
during development, also 
tend to be relatively stable traits over time. Negative symptoms that 
begin after psychosis onset 
are more variable and may reflect 
secondary causes. A degree of chronicity is required for a 
diagnosis of schizophrenia, and long-term 
course reflects a need for mental 
health care and living 
support 
in many individuals. While schizophrenia is generally not 
a progressive 
neurodegenerative disorder, life challenges, changing lifestyle, and persistent 
symptoms may 
lead to progressive dysfunction in more severe chronic cases. 


The essential 
features of schizophrenia are the same in childhood, but 
it 
is more difficult 
to 
make the diagnosis. In children, delusions and hallucinations may be less elaborate than in 
adults, and visual 
hallucinations are more common and should be distinguished from 
normal 
fantasy play. Disorganized speech occurs in many disorders with childhood onset 
(e.g., autism 
spectrum 
disorder), as does disorganized behavior (e.g., attention-deficit/hyperactivity disorder). 
These symptoms should not be attributed to schizophrenia 


118 


without 
due consideration of the more common disorders of childhood. Childhood-onset 
cases tend to resemble poor-outcome adult 
cases, with gradual 
onset 
and prominent 
negative 
symptoms. Children who later receive the diagnosis of schizophrenia are more likely to have 
experienced nonspecific emotional-behavioral 
disturbances and psychopathology, intellectual 
and language alterations, and subtle motor delays. 


Late-onset 
cases (i.e., onset 
after age 40 years) are overrepresented by women, who may 
have married. Often, the course is characterized by a predominance of psychotic symptoms with 
preservation of affect 
and social 
functioning. Such late-onset 
cases can still 
meet 
the diagnostic 
criteria for schizophrenia, but 
it 
is not 
yet 
clear whether this is the same condition as 
schizophrenia diagnosed prior to midlife (e.g., prior to age 55 years). 


Risk and Prognostic Factors 


Environmental. 
Season of birth has been linked to the incidence of schizophrenia, including late 



winter/early spring in some locations and summer for the deficit 
form 
of the disease. The 
incidence of schizophrenia and related disorders may be higher for children growing up in an 
urban environment, for refugees, for some migrant 
groups, and for socially oppressed groups 
facing discrimination. There is evidence that 
social 
deprivation, social 
adversity, and 
socioeconomic factors may be associated with increased rates of this disorder. Among 
individuals with schizophrenia and other psychotic disorders, the severity of positive and 
negative symptoms appears to be correlated with the severity of adverse childhood experiences, 
such as trauma and neglect. Higher rates of schizophrenia for some ethnic and racialized groups 
have been documented when they live in areas with lower proportions of people from 
the same 
ethnicity or racialized group. The reasons for this are not 
completely clear but 
appear related to 
several 
factors, including the following: 
1) higher levels of discrimination or fear of 
discrimination; 
2) less social 
support 
and more stigmatization of those with schizophrenia; 
3) 
higher social 
isolation; 
and 4) decreased availability of and access to normalizing explanations of 
perceptual 
experiences and abnormal 
beliefs reported by individuals at 
high risk for developing 
schizophrenia. 


Genetic 
and 
physiological. 
There is a strong contribution for genetic factors in determining risk for 
schizophrenia, although most 
individuals who have been diagnosed with schizophrenia have no 
family history of psychosis. Liability is conferred by a spectrum 
of risk alleles, common and 
rare, with each allele contributing only a small 
fraction to the total 
population variance. The risk 
alleles identified to date are also associated with other mental 
disorders, including bipolar 
disorder, depression, and autism spectrum disorder. 


Pregnancy and birth complications with hypoxia and greater paternal 
age are associated with 
a higher risk of schizophrenia for the developing fetus. In addition, other prenatal 
and perinatal 
adversities, including stress, infection, malnutrition, maternal 
diabetes, and other medical 
conditions, have been linked with schizophrenia. However, the vast 
majority of offspring with 
these risk factors do not develop schizophrenia. 


Culture-Related Diagnostic Issues 


The form 
and content 
of schizophrenia symptoms can vary cross-culturally, including the 
following ways: 
the relative proportion of visual 
and auditory hallucinations (e.g., while auditory 
hallucinations tend to be more common than visual 
hallucinations around the world, the relative 
proportion of visual 
hallucinations may be particularly higher in some regions compared with 
others); 
the specific content 
of the delusions (e.g., persecutory, grandiose, somatic) and 
hallucinations (e.g., command, abusive, religious); 
and the level 
of fear associated with them. 
Cultural 
and socioeconomic factors must 
be considered, particularly when the individual 
and the 
clinician do not 
share the same cultural 
and socioeconomic background. Ideas that 
appear to be 
delusional 
in one cultural 
context 
(e.g., evil 
eye, causing illness through curses, influences of 
spirits) may be commonly held in others. 


119 


In some cultural 
contexts, visual 
or auditory hallucinations with a religious content 
(e.g., hearing 
God s voice) are a normal 
part 
of religious experience. In addition, the assessment 
of 
disorganized speech may be made difficult 
by linguistic variation in narrative styles across 
cultures. The assessment 
of affect 
requires sensitivity to differences in styles of emotional 



expression, eye contact, and body language, which vary across cultures. If the assessment 
is 
conducted in a language that 
is different 
from 
the individual s primary language, care must 
be 
taken to ensure that 
alogia is not 
related to linguistic barriers. In certain cultures, distress may 
take the form 
of hallucinations or pseudo-hallucinations and overvalued ideas that 
may present 
clinically similar to true psychosis but 
are normative to the individual s subgroup. Misdiagnosis 
of schizophrenia in individuals with mood disorders with psychotic features or with other 
psychiatric disorders is more likely to occur in members of underserved ethnic and racialized 
groups (in the United States, especially among African Americans). This may be attributable to 
clinical 
bias, racism, or discrimination leading to limited quality of information and potential 
misinterpretation of symptoms. 


Sex- and Gender-Related Diagnostic Issues 


A number of features distinguish the clinical 
expression of schizophrenia in women and men. 
The age at 
onset 
is later in women, with a second midlife peak. Symptoms tend to be more 
affect-laden among women, and there are more psychotic symptoms, as well 
as a greater 
propensity for psychotic symptoms to worsen in later life. Other symptom 
differences include 
less frequent 
negative symptoms and disorganization. Finally, social 
functioning tends to remain 
better preserved in women. There are, however, frequent exceptions to these general caveats. 


Psychotic symptoms have been observed to worsen during the premenstrual 
time period 
when estrogen levels are dropping; 
consequently, increased psychiatric admission rates are seen 
in women with schizophrenia just 
before and during menses. Lower estrogen levels resulting 
from 
menopause may be another factor associated with the second peak of onset 
in women in 
midlife. Similarly, psychotic symptoms appear to improve during pregnancy when estrogen 
levels are high and worsen again postpartum when estrogen levels precipitously drop. 


Association With Suicidal 
Thoughts or Behavior 


Approximately 5% 6% of individuals with schizophrenia die by suicide, about 
20% attempt 
suicide on one or more occasions, and many more have significant 
suicidal 
ideation. Suicidal 
behavior is sometimes in response to command hallucinations to harm 
oneself or others. Suicide 
risk remains high over the whole lifespan for men and women, although it 
may be especially 
high for younger men with comorbid substance use. Other risk factors include depressive 
symptoms, hopelessness, being unemployed, the period after a psychotic episode or hospital 
discharge, number of psychiatric admissions, closeness to onset 
of illness, and older age at 
illness onset. A systematic review and meta-analysis of longitudinal 
studies found that 
the odds 
of suicidal 
behavior during follow-up after first-episode psychosis were higher among 
individuals with depressive symptoms during first-episode psychosis compared with those 
without. A meta-analysis of a large number of studies of the relationship of schizophrenia with 
suicidal 
behavior found that 
alcohol, tobacco, and drug abuse; 
depression; 
number of 
hospitalizations; 
physical 
comorbidity; 
and family history of depression and suicidal 
behavior 
increased the risk of suicide attempt. Risk factors for suicide included male sex, being younger, 
having a higher IQ, history of attempts, hopelessness, and poor adherence to treatment. 


Functional 
Consequences of Schizophrenia 


Schizophrenia is associated with significant 
social 
and occupational 
dysfunction. Among 



individuals with schizophrenia, deficits in reading ability are more severe than what would 


120 


be predicted by the general 
cognitive impairments associated with the disorder. Such deficits can 
be conceptualized as a secondary or acquired dyslexia that 
underlies the academic impairment 
observed in schizophrenia. Making educational 
progress and maintaining employment 
are 
frequently impaired by avolition or other disorder manifestations, even when the cognitive skills 
are sufficient 
for the tasks at 
hand. Most 
individuals are employed at 
a lower level 
than their 
parents, and most, particularly men, do not 
marry or have limited social 
contacts outside of their 
family. 


Differential 
Diagnosis 


Major depressive 
or bipolar disorder with 
psychotic 
or catatonic 
features. 


The distinction between 
schizophrenia and major depressive or bipolar disorder with psychotic features or with catatonia 
depends on the temporal 
relationship between the mood disturbance and the psychosis, and on 
the severity of the depressive or manic symptoms. If delusions or hallucinations occur 
exclusively during a major depressive or manic episode, the diagnosis is depressive or bipolar 
disorder with psychotic features. 


Schizoaffective 
disorder. 
A diagnosis of schizoaffective disorder requires that 
a major depressive 
or manic episode occur concurrently with the active-phase symptoms and that 
the mood 
symptoms be present for a majority of the total duration of the active periods. 


Schizophreniform disorder and 
brief 
psychotic 
disorder. 


These disorders are of shorter duration than 
schizophrenia as specified in Criterion C, which requires 6 months of symptoms. In 
schizophreniform 
disorder, the disturbance is present 
less than 6 months, and in brief psychotic 
disorder, symptoms are present at least 1 day but less than 1 month. 


Delusional 
disorder. 
Delusional 
disorder can be distinguished from 
schizophrenia by the absence 
of the other symptoms characteristic of schizophrenia (e.g., delusions, prominent 
auditory or 
visual 
hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative 
symptoms). 


Schizotypal 
personality 
disorder. 
Schizotypal 
personality disorder may be distinguished from 
schizophrenia by subthreshold symptoms that are associated with persistent personality features. 


Obsessive-compulsive 
disorder and 
body 
dysmorphic 
disorder. 


Individuals with obsessive-
compulsive disorder and body dysmorphic disorder may present 
with poor or absent 
insight, and 
the preoccupations may reach delusional 
proportions. But 
these disorders are distinguished from 
schizophrenia by their prominent 
obsessions, compulsions, preoccupations with appearance or 
body odor, hoarding, or body-focused repetitive behaviors. 


Posttraumatic 
stress 
disorder. 
Posttraumatic stress disorder may include flashbacks that 
have a 
hallucinatory quality, and hypervigilance may reach paranoid proportions. But 
a traumatic event 
and characteristic symptom 
features relating to reliving or reacting to the event 
are required to 
make the diagnosis of posttraumatic stress disorder. 
Autism spectrum disorder or communication 
disorders. 
These disorders may also have symptoms 


resembling a psychotic episode but 
are distinguished by their respective deficits in social 



interaction with repetitive and restricted behaviors and other cognitive and communication 
deficits. An individual 
with autism 
spectrum 
disorder or communication disorder must 
have 
symptoms that 
meet 
full 
criteria for schizophrenia, with prominent 
hallucinations or delusions 
for at least 1 month, in order to be diagnosed with schizophrenia as a comorbid condition. 
Other mental 
disorders 
associated 
with 
a 
psychotic 
episode. 
The diagnosis of schizophrenia is made 


only when the psychotic episode is persistent 
and not 
attributable to the physiological 
effects of a 
substance or another medical 
condition. Individuals with a delirium 
or major or minor 
neurocognitive disorder may present with psychotic symptoms, 


121 


but 
these would have a temporal 
relationship to the onset 
of cognitive changes consistent 
with 
those disorders. 
Substance/medication-induced 
psychotic 
disorder. 
Individuals with substance/medication-induced 


psychotic disorder may present 
with symptoms characteristic of Criterion A for schizophrenia, 
but 
the substance/medication-induced psychotic disorder can usually be distinguished by the 
chronological 
relationship of substance use to the onset 
and remission of the psychosis in the 
absence of substance use. 


Comorbidity 


Rates of comorbidity with substance-related disorders are high in schizophrenia. Over half of 
individuals with schizophrenia have tobacco use disorder and smoke cigarettes regularly. 
Comorbidity with anxiety disorders is increasingly recognized in schizophrenia. Rates of 
obsessive-compulsive disorder and panic disorder are elevated in individuals with schizophrenia 
compared with the general 
population. Schizotypal 
or paranoid personality disorder may 
sometimes precede the onset of schizophrenia. 


Life expectancy is reduced in individuals with schizophrenia because of associated medical 
conditions. Weight 
gain, diabetes, metabolic syndrome, and cardiovascular and pulmonary 
disease are more common in schizophrenia than in the general 
population. Poor engagement 
in 
health maintenance behaviors (e.g., cancer screening, exercise) increases the risk of chronic 
disease, but 
other disorder factors, including medications, lifestyle, cigarette smoking, and diet, 
may also play a role. A shared vulnerability for psychosis and medical 
conditions may explain 
some of the medical comorbidity of schizophrenia. 


Schizoaffective Disorder 


Diagnostic Criteria 


A. 
An 
uninterrupted 
period 
of 
illness during 
which 
there 
is a 
major mood 
episode 
(major depressive 
or manic) concurrent 
with 
Criterion 
A 
of 
schizophrenia. 
Note: 
The 
major depressive 
episode 
must 
include 
Criterion 
A1: 
Depressed 
mood. 



B. 
Delusions or hallucinations for 2 
or more 
weeks in 
the 
absence 
of 
a 
major mood 
episode 
(depressive 
or manic) during 
the 
lifetime 
duration 
of 
the 
illness. 
C. 
Symptoms that 
meet 
criteria 
for a 
major mood 
episode 
are 
present 
for the 
majority of 
the 
total duration 
of 
the 
active 
and 
residual portions of 
the 
illness. 
D. 
The 
disturbance 
is not 
attributable 
to 
the 
effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition. 
Specify 
whether: 
F25.0 
Bipolar type: 
This subtype 
applies if 
a 
manic episode 
is part 
of 
the 
presentation. 
Major depressive 
episodes may also 
occur. 


F25.1 
Depressive 
type: 
This subtype 
applies if 
only major depressive 
episodes 
are 
part 
of 
the 
presentation. 


Specify 
if: 
With 
catatonia 
(refer to 
the 
criteria 
for catatonia 
associated 
with 
another mental 
disorder, 
p. 
135, 
for definition). 


Coding 
note: 
Use 
additional code 
F06.1 
catatonia 
associated 
with 
schizoaffective 
disorder to 
indicate 
the 
presence 
of 
the 
comorbid 
catatonia. 


Specify 
if: 
The 
following 
course 
specifiers are 
only to 
be 
used 
after a 
1-year duration 
of 
the 
disorder and 
if 
they are 
not 
in 
contradiction 
to 
the 
diagnostic course 
criteria. 


122 


First episode, 
currently 
in 
acute 
episode: 
First 
manifestation 
of 
the 
disorder 
meeting 
the 
defining 
diagnostic symptom and 
time 
criteria. 
An 
acute 
episode 
is a 
time 
period 
in 
which 
the 
symptom criteria 
are 
fulfilled. 


First episode, 
currently 
in 
partial 
remission: 
Partial remission 
is a 
time 
period 
during 
which 
an 
improvement 
after a 
previous episode 
is maintained 
and 
in 
which 
the 
defining 
criteria 
of 
the 
disorder are 
only partially fulfilled. 


First episode, 
currently 
in 
full 
remission: 
Full remission 
is a 
period 
of 
time 
after a 
previous episode 
during 
which 
no 
disorder-specific symptoms are 
present. 


Multiple 
episodes, 
currently 
in 
acute 
episode: 
Multiple 
episodes may be 
determined 
after a 
minimum of 
two 
episodes (i.e., 
after a 
first 
episode, 
a 
remission 
and 
a 
minimum of 
one 
relapse). 


Multiple 
episodes, 
currently 
in 
partial 
remission 
Multiple 
episodes, 
currently 
in 
full 
remission 
Continuous: 
Symptoms fulfilling 
the 
diagnostic symptom criteria 
of 
the 
disorder 


are 
remaining 
for the 
majority of 
the 
illness course, 
with 
subthreshold 
symptom 
periods being 
very brief 
relative 
to 
the 
overall course. 


Unspecified 


Specify 
current 
severity: 



Severity is rated 
by a 
quantitative 
assessment 
of 
the 
primary symptoms of 
psychosis, 
including 
delusions, 
hallucinations, 
disorganized 
speech, 
abnormal 
psychomotor behavior, 
and 
negative 
symptoms. 
Each 
of these 
symptoms may 
be 
rated 
for its current 
severity (most 
severe 
in 
the 
last 7 
days) on 
a 
5-point 
scale 
ranging 
from 0 
(not 
present) to 
4 
(present 
and 
severe). 
(See 
Clinician-
Rated 
Dimensions of 
Psychosis Symptom Severity in 
the 
chapter  Assessment 
Measures. ) 


Note: 
Diagnosis of 
schizoaffective 
disorder can 
be 
made 
without 
using 
this 
severity specifier. 


Diagnostic Features 


The diagnosis of schizoaffective disorder is based on the assessment 
of an uninterrupted period 
of illness during which the individual 
continues to display active or residual 
symptoms of 
psychotic illness. The diagnosis is usually, but 
not 
necessarily, made during the period of 
psychotic illness. At 
some time during the period, Criterion A for schizophrenia has to be met. 
Criteria B 
(social 
dysfunction), C 
(6-month duration), and F 
(exclusion of autism 
spectrum 
disorder or other communication disorder of childhood onset) for schizophrenia do not 
have to 
be met. In addition to meeting Criterion A for schizophrenia, there is a major mood episode 
(major depressive or manic) (Criterion A for schizoaffective disorder). Because loss of interest or 
pleasure is common in schizophrenia, to meet 
Criterion A for schizoaffective disorder, the major 
depressive episode must 
include pervasive depressed mood (i.e., the presence of markedly 
diminished interest 
or pleasure is not 
sufficient). Episodes of depression or mania are present 
for 
the majority of the total 
duration of the illness (i.e., after Criterion A has been met) (Criterion C 
for schizoaffective disorder). To separate schizoaffective disorder from 
a depressive or bipolar 
disorder with psychotic features, delusions or hallucinations must 
be present 
for at 
least 
2 weeks 
in the absence of a major mood episode (depressive or manic) at 
some point 
during the lifetime 
duration of the illness (Criterion B 
for schizoaffective disorder). The symptoms must 
not 
be 
attributable to the effects of a substance or another medical 
condition (Criterion D for 
schizoaffective disorder). 


Criterion C 
for schizoaffective disorder specifies that 
mood symptoms meeting criteria for a 
major mood episode must 
be present 
for the majority of the total 
duration of the active and 
residual 
portion of the illness. Criterion C 
requires the assessment 
of mood symptoms for the 
entire lifetime course of a psychotic illness. If the mood symptoms are present 


123 


for only a relatively brief period, the diagnosis is schizophrenia, not 
schizoaffective disorder. 
When deciding whether an individual s presentation meets Criterion C, the clinician should 
review the total 
duration of psychotic illness (i.e., both active and residual 
symptoms) and 
determine when significant 
mood symptoms (untreated or in need of treatment 
with 
antidepressant 
and/or mood-stabilizing medication) accompanied the psychotic symptoms. This 
determination requires sufficient 
historical 
information and clinical 
judgment. For example, an 
individual 
with a 4-year history of active and residual 
symptoms of schizophrenia develops 
depressive and manic episodes that, taken together, do not 
occupy more than 1 year during the 4



year history of psychotic illness. This presentation would not meet Criterion C. 


In addition to the five symptom 
domain areas identified in the diagnostic criteria, the 
assessment 
of cognition, depression, and mania symptom 
domains is vital 
for making critically 
important distinctions between the various schizophrenia spectrum and other psychotic disorders. 


Associated Features 


Occupational 
and social 
functioning is frequently impaired, but 
this is not 
a defining criterion (in 
contrast 
to schizophrenia). Restricted social 
contact 
and difficulties with self-care are associated 
with schizoaffective disorder, but 
negative symptoms may be less severe and less persistent 
than 
those seen in schizophrenia. Anosognosia (i.e., poor insight) is also common in schizoaffective 
disorder, but 
the deficits in insight 
may be less severe and pervasive than those in schizophrenia. 
Individuals with schizoaffective disorder may be at 
increased risk for later developing episodes 
of major depressive disorder or bipolar disorder if mood symptoms continue following the 
remission of symptoms meeting Criterion A for schizophrenia. There may be associated alcohol 
and other substance-related disorders. 


There are no tests or biological 
measures that 
can provide definitive assistance in making the 
diagnosis of schizoaffective disorder. Neuropsychological 
testing typically shows cognitive 
deficits in areas such as executive function, verbal 
memory, and speed of processing, and these 
may be less pronounced than in schizophrenia. Schizoaffective disorder is often characterized by 
gray matter volume loss on brain imaging, in much the same way that schizophrenia is. 


Prevalence 


Schizoaffective disorder appears to be about 
one-third as common as schizophrenia. Lifetime 
prevalence of schizoaffective disorder was estimated to be 0.3% in a Finnish sample and is 
higher in women than in men when DSM-IV diagnostic criteria were used. This rate would be 
expected to be lower because of the more stringent 
requirement 
of DSM-5 Criterion C 
(i.e., 
mood symptoms meeting criteria for a major mood episode must 
be present 
for the majority of 
the total duration of the active and residual portion of the illness). 


Development and Course 


The typical 
age at 
onset 
of schizoaffective disorder is early adulthood, although onset 
can occur 
anytime from 
adolescence to late in life. A significant 
number of individuals diagnosed with 
another psychotic illness initially will 
receive the diagnosis schizoaffective disorder later when 
the pattern of mood episodes has become more apparent, whereas others may be diagnosed with 
mood disorders before independent psychotic symptoms are detected. 


Conversely, some individuals will 
have a change in diagnosis from 
schizoaffective disorder 
to a mood disorder or to schizophrenia over time. A change in diagnosis from 
schizoaffective 
disorder to schizophrenia was more common than a change to mood disorder 


124 


under DSM-IV criteria, and that 
difference is expected to be more pronounced under DSM-5 
as the current 
Criterion C 
for schizoaffective disorder has become more stringent, requiring 
mood symptoms to be present 
for the majority of the illness as compared with the DSM-IV 
definition, which only required mood symptoms to be present 
for a  substantial  portion. The 



prognosis for schizoaffective disorder is somewhat 
better than the prognosis for schizophrenia 
but worse than the prognosis for mood disorders. 


Schizoaffective disorder may occur in a variety of temporal 
patterns. The following is a 
typical 
pattern: 
An individual 
may have pronounced auditory hallucinations and persecutory 
delusions for 2 months before the onset 
of a prominent 
major depressive episode. The psychotic 
symptoms and the full 
major depressive episode are then present 
for 4 months. Then, the 
individual 
recovers completely from 
the major depressive episode, but 
the psychotic symptoms 
persist 
for another month before they too disappear. During this period of illness, the individual s 
symptoms concurrently met 
criteria for a major depressive episode and Criterion A for 
schizophrenia, and during this same period of illness, auditory hallucinations and delusions were 
present 
both before and after the depressive phase. The total 
period of illness lasted for about 
7 
months, with psychotic symptoms alone present 
during the initial 
2 months, both depressive and 
psychotic symptoms present 
during the next 
4 months, and psychotic symptoms alone present 
during the last 
month. In this instance, the depressive episode was present 
for a majority of the 
total 
duration of the psychotic disturbance, and thus the presentation qualifies for a diagnosis of 
schizoaffective disorder. 


The temporal 
relationship between the mood symptoms and the psychotic symptoms across 
the lifespan is variable. Depressive or manic symptoms can occur before the onset 
of psychosis, 
during acute psychotic episodes, during residual 
periods, and after cessation of psychosis. For 
example, an individual 
might 
present 
with prominent 
mood symptoms during the prodromal 
stage of schizophrenia. This pattern is not 
necessarily indicative of schizoaffective disorder, 
since it 
is the co-occurrence of psychotic and mood symptoms that 
is diagnostic. For an 
individual 
with symptoms that 
clearly meet 
the criteria for schizoaffective disorder but 
who on 
further follow-up only presents with residual 
psychotic symptoms (such as subthreshold 
psychosis and/or prominent negative symptoms), the diagnosis may be changed to schizophrenia, 
as the total 
proportion of psychotic illness compared with mood symptoms becomes more 
prominent. Schizoaffective disorder, bipolar type, may be more common in young adults, 
whereas schizoaffective disorder, depressive type, may be more common in older adults. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Among individuals with schizophrenia, there may be an increased risk 
for schizoaffective disorder in first-degree relatives. The risk for schizoaffective disorder may 
also be increased among individuals who have a first-degree relative with bipolar disorder or 
schizoaffective disorder itself. The molecular genetic composite signatures known as polygenic 
risk scores for schizophrenia, bipolar disorder, and major depressive disorder may all 
be elevated 
in schizoaffective disorder. 


Culture-Related Diagnostic Issues 


Cultural 
and socioeconomic factors must 
be considered, particularly when the individual 
and the 
clinician do not 
share the same cultural 
and economic background. Ideas that 
appear to be 
delusional 
in one cultural 
context 
(e.g., evil 
eye, causing illness through curses, influences of 
spirits) may be commonly held in others. There is also some evidence in the literature that 
African American and Hispanic populations whose symptoms meet 
criteria for schizoaffective 
disorder are more likely to be diagnosed with schizophrenia. To mitigate the impact 
of clinician 



bias, care must 
be taken to ensure a comprehensive evaluation that 
includes both psychotic and 
mood symptoms. 


125 


Association With Suicidal 
Thoughts or Behavior 


The lifetime risk of suicide for schizophrenia and schizoaffective disorder is 5%, and the 
presence of depressive symptoms is correlated with a higher risk for suicide. There is evidence 
that 
suicide rates are higher in North American populations than in European, Eastern European, 
South American, and Indian populations of individuals with schizophrenia or schizoaffective 
disorder. 


Functional 
Consequences of Schizoaffective Disorder 


Schizoaffective disorder is associated with global 
dysfunction, including in social 
and 
occupational 
domains, but 
dysfunction is not 
a diagnostic criterion (as it 
is for schizophrenia), 
and there is substantial variability between individuals diagnosed with schizoaffective disorder. 


Differential 
Diagnosis 


Other mental 
disorders 
and 
medical 
conditions. 
A wide variety of psychiatric and medical 
conditions 
can manifest 
with psychotic and mood symptoms and must 
be considered in the differential 
diagnosis of schizoaffective disorder. These include delirium; major neurocognitive disorder; 
substance/medication-induced psychotic disorder or neurocognitive disorder; 
bipolar disorders, 
with psychotic features; 
major depressive disorder, with psychotic features; 
depressive or bipolar 
disorders, with catatonic features; 
schizotypal, schizoid, or paranoid personality disorder; 
brief 
psychotic disorder; 
schizophreniform 
disorder; 
schizophrenia; 
delusional 
disorder; 
and other 
specified and unspecified schizophrenia spectrum and other psychotic disorders. 


Psychotic 
disorder due 
to 
another medical 
condition. 


Other medical 
conditions and substance use can 
manifest 
with a combination of psychotic and mood symptoms, and thus psychotic disorder due 
to another medical condition needs to be excluded. 
Schizophrenia, 
bipolar, 
and 
depressive 
disorders. 
Distinguishing schizoaffective disorder from 


schizophrenia and from 
depressive and bipolar disorders with psychotic features is often 
difficult. Criterion C 
is designed to separate schizoaffective disorder from 
schizophrenia, and 
Criterion B 
is designed to distinguish schizoaffective disorder from 
a depressive or bipolar 
disorder with psychotic features. More specifically, schizoaffective disorder can be distinguished 
from 
a major depressive or bipolar disorder with psychotic features based on the presence of 
prominent 
delusions and/or hallucinations for at 
least 
2 weeks in the absence of a major mood 
episode. In contrast, in depressive or bipolar disorder with psychotic features, the psychotic 
features only occur during the mood episode(s). Because the relative proportion of mood to 
psychotic symptoms may change over time, the appropriate diagnosis may change from 
and to 
schizoaffective disorder. (For example, a diagnosis of schizoaffective disorder for a severe and 
prominent 
major depressive episode lasting 4 months during the first 
6 months of a chronic 
psychotic illness would be changed to schizophrenia if active psychotic or prominent 
residual 
symptoms persist 
over several 
years without 
a recurrence of another mood episode.) Achieving 
greater clarity about 
the relative proportion of mood to psychotic symptoms over time and about 



their concurrence may require collateral information from medical records and from informants. 


Comorbidity 


Many individuals diagnosed with schizoaffective disorder are also diagnosed with other mental 
disorders, especially substance use disorders and anxiety disorders. Similarly, the incidence of 
medical 
conditions, including metabolic syndrome, is increased above base rate for the general 
population and leads to decreased life expectancy. 


126 


Substance/Medication-Induced 
Psychotic Disorder 


Diagnostic Criteria 


A. 
Presence 
of 
one 
or both 
of 
the 
following 
symptoms: 
1. 
Delusions. 
2. 
Hallucinations. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
of 
both 
(1) and 
(2): 
1. 
The 
symptoms in 
Criterion 
A 
developed 
during 
or soon 
after substance 
intoxication 
or withdrawal or after exposure 
to 
or withdrawal from a 
medication. 
2. 
The 
involved 
substance/medication 
is capable 
of 
producing 
the 
symptoms in 
Criterion 
A. 
C. 
The 
disturbance 
is not 
better explained 
by a 
psychotic disorder that 
is not 
substance/medication-induced. 
Such 
evidence 
of 
an 
independent 
psychotic 
disorder could 
include 
the 
following: 
The 
symptoms preceded 
the 
onset 
of 
the 
substance/medication 
use; 
the 
symptoms persist 
for a 
substantial period 
of 
time 
(e.g., 
about 
1 
month) after 
the 
cessation 
of 
acute 
withdrawal or severe 
intoxication; 
or there 
is other 
evidence 
of 
an 
independent 
non-substance/medication-induced 
psychotic 
disorder (e.g., 
a 
history of 
recurrent 
non-substance/medication-related 
episodes). 


D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Note: 
This diagnosis should 
be 
made 
instead 
of 
a 
diagnosis of 
substance 
intoxication 
or substance 
withdrawal only when 
the 
symptoms in 
Criterion 
A 
predominate 
in 
the 
clinical picture 
and 
when 
they are 
sufficiently severe 
to 
warrant 
clinical attention. 



Coding 
note: 
The 
ICD-10-CM codes for the 
[specific substance/medication]-induced 
psychotic disorders are 
indicated 
in 
the 
table 
below. 
Note 
that 
the 
ICD-10-CM code 
depends on 
whether or not 
there 
is a 
comorbid 
substance 
use 
disorder present 
for 
the 
same 
class of 
substance. 
In 
any case, 
an 
additional separate 
diagnosis of 
a 
substance 
use 
disorder is not 
given. 
If 
a 
mild 
substance 
use 
disorder is comorbid 
with 
the 
substance-induced 
psychotic disorder, 
the 
4th 
position 
character is  1,  and 
the 
clinician 
should 
record 
 mild 
[substance] 
use 
disorder  before 
the 
substance-
induced 
psychotic disorder (e.g., 
 mild 
cocaine 
use 
disorder with 
cocaine-induced 
psychotic disorder ). 
If 
a 
moderate 
or severe 
substance 
use 
disorder is comorbid 
with 
the 
substance-induced 
psychotic disorder, 
the 
4th 
position 
character is  2,  and 
the 
clinician 
should 
record 
 moderate 
[substance] 
use 
disorder  or  severe 
[substance] 
use 
disorder,  depending 
on 
the 
severity of 
the 
comorbid 
substance 
use 
disorder. 
If 
there 
is no 
comorbid 
substance 
use 
disorder (e.g., 
after a 
one-time 
heavy 
use 
of 
the 
substance), 
then 
the 
4th 
position 
character is  9,  and 
the 
clinician 
should 
record 
only the 
substance-induced 
psychotic disorder. 


127 


ICD-10-CM 


With 
mild 
use 
With 
moderate 
or 
Without 
use 
disorder 
severe 
use 
disorder 
disorder 
Alcohol 
F10.159 
F10.259 
F10.959 
Cannabis 
F12.159 
F12.259 
F12.959 
Phencyclidine 
F16.159 
F16.259 
F16.959 
Other 
hallucinogen 
F16.159 
F16.259 
F16.959 
Inhalant 
F18.159 
F18.259 
F18.959 
Sedative, 
hypnotic, 
or 
anxiolytic 
F13.159 
F13.259 
F13.959 
Amphetamine-type 
substance 
(or 
other 
stimulant) 
F15.159 
F15.259 
F15.959 
Cocaine 
F14.159 
F14.259 
F14.959 
Other 
(or 
unknown) 
substance 
F19.159 
F19.259 
F19.959 


Specify 
(see 
Table 
1 
in 
the 
chapter  Substance-Related 
and 
Addictive 
Disorders,  
which 
indicates whether  with 
onset 
during 
intoxication  and/or  with 
onset 
during 
withdrawal  applies to 
a 
given 
substance 
class; 
or specify 
 with 
onset 
after 
medication 
use ): 


With 
onset during 
intoxication: 
If 
criteria 
are 
met 
for intoxication 
with 
the 


substance 
and 
the 
symptoms develop 
during 
intoxication. 
With 
onset during 
withdrawal: 
If 
criteria 
are 
met 
for withdrawal from the 
substance 
and 
the 
symptoms develop 
during, 
or shortly after, 
withdrawal. 


With 
onset after medication 
use: 
If 
symptoms developed 
at 
initiation 
of 
medication, 
with 
a 
change 
in 
use 
of 
medication, 
or during 
withdrawal of 
medication. 



Specify 
current 
severity: 
Severity is rated 
by a 
quantitative 
assessment 
of 
the 
primary symptoms of 
psychosis, 
including 
delusions, 
hallucinations, 
abnormal psychomotor behavior, 
and 
negative 
symptoms. 
Each 
of 
these 
symptoms may be 
rated 
for its current 
severity (most 
severe 
in 
the 
last 
7 
days) on 
a 
5-point 
scale 
ranging 
from 0 
(not 


present) to 
4 
(present 
and 
severe). 
(See 
Clinician-Rated 
Dimensions of 
Psychosis Symptom Severity in 
the 
chapter  Assessment 
Measures. ) 
Note: 
Diagnosis of 
substance/medication-induced 
psychotic disorder can 
be 


made 
without 
using 
this severity specifier. 


Recording Procedures 


The name of the substance/medication-induced psychotic disorder begins with the specific 
substance (e.g., cocaine, dexamethasone) that 
is presumed to be causing the delusions or 
hallucinations. The diagnostic code is selected from 
the table included in the criteria set, which is 
based on the drug class and presence or absence of a comorbid substance use disorder. For 
substances that 
do not 
fit 
into any of the classes (e.g., dexamethasone), the code for  other (or 
unknown) substance  should be used; 
and in cases in which a substance is judged to be an 
etiological 
factor but 
the specific class of substance is unknown, the same code should also be 
used. 


128 


When recording the name of the disorder, the comorbid substance use disorder (if any) is 
listed first, followed by the word  with,  followed by the name of the substance-induced 
psychotic disorder, followed by the specification of onset 
(i.e., onset 
during intoxication, onset 
during withdrawal). For example, in the case of delusions occurring during intoxication in a man 
with a severe cocaine use disorder, the diagnosis is F14.259 severe cocaine use disorder with 
cocaine-induced psychotic disorder, with onset 
during intoxication. A separate diagnosis of the 
comorbid severe cocaine use disorder is not 
given. If the substance-induced psychotic disorder 
occurs without 
a comorbid substance use disorder (e.g., after a one-time heavy use of the 
substance), no accompanying substance use disorder is noted (e.g., F16.959 phencyclidineinduced 
psychotic disorder, with onset 
during intoxication). When more than one substance is 
judged to play a significant role in the development of psychotic symptoms, each should be listed 
separately (e.g., F12.259 severe cannabis use disorder with cannabis-induced psychotic disorder, 
with onset 
during intoxication; 
F16.159 mild phencyclidine use disorder with phencyclidineinduced 
psychotic disorder, with onset during intoxication). 


Diagnostic Features 


The essential 
features of substance/medication-induced psychotic disorder are prominent 
delusions and/or hallucinations (Criterion A) that 
are judged to be due to the physiological 
effects of a substance/medication (i.e., a drug of abuse, a medication, or a toxin exposure) 
(Criterion B). Hallucinations that 
the individual 
realizes are substance/medication-induced are 
not 
included here and instead would be diagnosed as substance intoxication or substance 
withdrawal 
with the accompanying specifier  with perceptual 
disturbances  (applies to alcohol 



withdrawal; 
cannabis intoxication; 
sedative, hypnotic, or anxiolytic withdrawal; 
and stimulant 
intoxication). 


A substance/medication-induced psychotic disorder is distinguished from 
an independent 
psychotic disorder by considering the onset, course, and other factors. For drugs of abuse, there 
must 
be evidence from 
the history, physical 
examination, or laboratory findings of substance use, 
intoxication, or withdrawal. Substance/medication-induced psychotic disorders arise during or 
soon after exposure to or withdrawal 
from 
a medication or after substance intoxication or 
withdrawal 
but 
can persist 
for weeks, whereas independent 
psychotic disorders may precede the 
onset 
of substance/medication use or may occur during times of sustained abstinence. Once 
initiated, the psychotic symptoms may continue as long as the substance/medication use 
continues. Another consideration is the presence of features that 
are atypical 
of an independent 
psychotic disorder (e.g., atypical 
age at 
onset 
or course). For example, the appearance of 
delusions de novo in a male person older than 35 years without 
a known history of an 
independent 
psychotic disorder should suggest 
the possibility of a substance/medication-induced 
psychotic disorder. Even a prior history of an independent 
psychotic disorder does not 
rule out 
the possibility of a substance/medication-induced psychotic disorder. In contrast, factors that 
suggest 
that 
the psychotic symptoms are better accounted for by an independent 
psychotic 
disorder include persistence of psychotic symptoms for a substantial 
period of time (i.e., a month 
or more) after the end of substance intoxication or acute substance withdrawal 
or after cessation 
of medication use; 
or a history of prior recurrent 
independent 
psychotic disorders. Other causes 
of psychotic symptoms must 
be considered even in an individual 
with substance intoxication or 
withdrawal, because substance use problems are not 
uncommon among individuals with non-
substance/medication-induced psychotic disorders. 


In addition to the two symptom 
domain areas identified in the diagnostic criteria (i.e., 
delusions and hallucinations), the assessment 
of cognition, depression, and mania symptom 
domains is vital 
for making critically important 
distinctions between the various schizophrenia 
spectrum and other psychotic disorders. 


129 


Associated Features 


Psychotic disorders can occur in association with intoxication with the following classes of 
substances: 
alcohol; 
cannabis; 
hallucinogens, including phencyclidine and related substances; 
inhalants; 
sedatives, hypnotics, and anxiolytics; 
stimulants (including cocaine); 
and other (or 
unknown) substances. Psychotic disorders can occur in association with withdrawal 
from 
the 
following classes of substances: 
alcohol; 
sedatives, hypnotics, and anxiolytics; 
and other (or 
unknown) substances. 


Some of the medications reported to evoke psychotic symptoms include anesthetics and 
analgesics, anticholinergic agents, anticonvulsants, antihistamines, antihypertensive and 
cardiovascular medications, antimicrobial 
medications, antiparkinsonian medications, 
chemotherapeutic agents (e.g., cyclosporine, procarbazine), corticosteroids, gastrointestinal 
medications, muscle relaxants, nonsteroidal 
anti-inflammatory medications, other over-thecounter 
medications (e.g., phenylephrine, pseudoephedrine), antidepressant 
medication, and 
disulfiram. Toxins reported to induce psychotic symptoms include anticholinesterase, 



organophosphate insecticides, sarin and other nerve gases, carbon monoxide, carbon dioxide, and 
volatile substances such as fuel or paint. 


Prevalence 


Prevalence of substance/medication-induced psychotic disorder in the general 
population is 
unknown. Between 7% and 25% of individuals presenting with a first 
episode of psychosis in 
different settings are reported to have substance/medication-induced psychotic disorder. 


Development and Course 


The initiation of the psychotic symptoms may vary considerably with the substance. For 
example, smoking a high dose of cocaine may produce psychosis within minutes, whereas days 
or weeks of high-dose alcohol 
or sedative use may be required to produce psychosis. Alcohol-
induced psychotic disorder, with hallucinations, usually occurs only after prolonged, heavy 
ingestion of alcohol 
in individuals who have moderate to severe alcohol 
use disorder, and the 
hallucinations are generally auditory in nature. 


Psychotic disorders induced by amphetamine-type substances and cocaine share similar 
clinical 
features. Persecutory delusions may rapidly develop shortly after use of amphetamine or 
a similarly acting sympathomimetic. The hallucination of bugs or vermin crawling in or under 
the skin (formication) can lead to scratching and extensive skin excoriations. Cannabis-induced 
psychotic disorder may develop shortly after high-dose cannabis use and usually involves 
persecutory delusions, marked anxiety, emotional 
lability, and 
depersonalization. The disorder 
usually remits within a day but in some cases may persist longer. 


Substance/medication-induced psychotic disorder may at 
times persist 
when the offending 
agent 
is removed, such that 
it 
may be difficult 
initially to distinguish it 
from 
an independent 
psychotic disorder. Agents such as amphetamine-type substances, phencyclidine, and cocaine 
have been reported to evoke temporary psychotic states that 
can sometimes persist 
for weeks or 
longer despite removal 
of the agent 
and treatment 
with neuroleptic medication. In later life, 
polypharmacy for medical 
conditions and exposure to medications for parkinsonism, 
cardiovascular disease, and other medical 
disorders may be associated with a greater likelihood 
of psychosis induced by prescription medications as opposed to substances of abuse. 


According to data from 
a Danish registry study that 
followed cases of substance-induced 
psychosis longitudinally over 20 years, roughly one-third (32%) of individuals with substance-
induced psychosis are later diagnosed with a schizophrenia spectrum 
disorder (26%) or a bipolar 
disorder (8%), with the highest rate (44%) for cannabis-induced psychotic disorder. 


130 


Diagnostic Markers 


With substances for which relevant 
blood levels are available (e.g., blood alcohol 
level, other 
quantifiable blood levels such as digoxin), the presence of a level 
consistent 
with toxicity may 
increase diagnostic certainty. 


Functional 
Consequences of Substance/Medication-Induced Psychotic 
Disorder 



Substance/medication-induced psychotic disorder is typically severely disabling and 
consequently is observed most 
frequently in emergency departments, as individuals are often 
brought 
to the acute-care setting when it 
occurs. However, the disability is typically self-limited 
and resolves upon removal of the offending agent. 


Differential 
Diagnosis 


Substance 
intoxication 
or substance 
withdrawal. 


Individuals intoxicated with stimulants, cannabis, 
the opioid meperidine, or phencyclidine, or those withdrawing from 
alcohol 
or sedatives, may 
experience altered perceptions that 
they recognize as drug effects. If reality testing for these 
experiences remains intact 
(i.e., the individual 
recognizes that 
the perception is substance 
induced and neither believes in nor acts on it), the diagnosis is not 
substance/medication-induced 
psychotic disorder. Instead, substance intoxication or substance withdrawal, with perceptual 
disturbances, is diagnosed (e.g., cocaine intoxication, with perceptual 
disturbances).  Flashback  
hallucinations that 
can occur long after the use of hallucinogens has stopped are diagnosed as 
hallucinogen persisting perception disorder. If substance/medication-induced psychotic 
symptoms occur exclusively during the course of a delirium, as in severe forms of alcohol 
withdrawal, the psychotic symptoms are considered to be an associated feature of the delirium 
and are not 
diagnosed separately. Delusions in the context 
of a major or mild neurocognitive 
disorder would be diagnosed as major or mild neurocognitive disorder, with behavioral 
disturbance. 


Independent 
psychotic 
disorder. 
A substance/medication-induced psychotic disorder is 
distinguished from 
an independent 
psychotic disorder, such as schizophrenia, schizoaffective 
disorder, delusional 
disorder, brief psychotic disorder, other specified schizophrenia spectrum 
and other psychotic disorder, or unspecified schizophrenia spectrum 
and other psychotic 
disorder, by the fact that a substance is judged to be etiologically related to the symptoms. 
Psychotic 
disorder due 
to 
another medical 
condition. 
A substance/medication-induced psychotic 


disorder due to a prescribed treatment 
for a mental 
disorder or medical 
condition must 
have its 
onset 
while the individual 
is receiving the medication (or during withdrawal, if there is a 
withdrawal 
syndrome associated with the medication). Because individuals with medical 
conditions often take medications for those conditions, the clinician must 
consider the possibility 
that 
the psychotic symptoms are caused by the physiological 
consequences of the medical 
condition itself rather than the medication, in which case psychotic disorder due to another 
medical 
condition is diagnosed. The history often provides the primary basis for such a 
judgment. At 
times, a change in the treatment 
for the medical 
condition (e.g., medication 
substitution or discontinuation) may be needed to determine empirically for that 
individual 
whether the medication is the causative agent. If the clinician has ascertained that 
the disturbance 
is attributable to both a medical 
condition and substance/medication use, both diagnoses (i.e., 
psychotic disorder due to another medical 
condition and substance/medication-induced psychotic 
disorder) may be given. 
Other specified 
or unspecified 
schizophrenia 
spectrum and 
other psychotic 
disorder. 
The psychotic 


symptoms included in the diagnosis of substance/medication-induced psy-chotic disorder are 
limited to either delusions or hallucinations. Individuals with other 


131 



substance-induced psychotic symptoms (e.g., disorganized or catatonic behavior; 
disorganized 
speech; 
incoherence or irrational 
content) should be classified in the category other specified or 
unspecified schizophrenia spectrum and other psychotic disorder. 


Psychotic Disorder Due to 
Another Medical 
Condition 


Diagnostic Criteria 


A. 
Prominent 
hallucinations or delusions. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
that 
the 
disturbance 
is the 
direct 
pathophysiological consequence 
of 
another 
medical condition. 
C. 
The 
disturbance 
is not 
better explained 
by another mental disorder. 
D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Specify 
whether: 
Code 
based 
on 
predominant 
symptom: 
F06.2 
With 
delusions: 
If 
delusions are 
the 
predominant 
symptom. 
F06.0 
With 
hallucinations: 
If 
hallucinations are 
the 
predominant 
symptom. 
Coding 
note: 
Include 
the 
name 
of 
the 
other medical condition 
in 
the 
name 
of 
the 
mental disorder (e.g., 
F06.2 
psychotic disorder due 
to 
malignant 
lung 
neoplasm, 
with 
delusions). 
The 
other medical condition 
should 
be 
coded 
and 
listed 
separately 
immediately before 
the 
psychotic disorder due 
to 
the 
medical condition 
(e.g., 
C34.90 
malignant 
lung 
neoplasm; 
F06.2 
psychotic disorder due 
to 
malignant 
lung 
neoplasm, 
with 
delusions). 


Specify 
current 
severity: 


Severity is rated 
by a 
quantitative 
assessment 
of 
the 
primary symptoms of 


psychosis, 
including 
delusions, 
hallucinations, 
abnormal psychomotor behavior, 


and 
negative 
symptoms. 
Each 
of 
these 
symptoms may be 
rated 
for its current 


severity (most 
severe 
in 
the 
last 
7 
days) on 
a 
5-point 
scale 
ranging 
from 0 
(not 


present) to 
4 
(present 
and 
severe). 
(See 
Clinician-Rated 
Dimensions of 


Psychosis Symptom Severity in 
the 
chapter  Assessment 
Measures. ) 


Note: 
Diagnosis of 
psychotic disorder due 
to 
another medical condition 
can 
be 


made 
without 
using 
this severity specifier. 


Specifiers 


In addition to the symptom 
domain areas identified in the diagnostic criteria, the assessment 
of 
cognition, depression, and mania symptom 
domains is vital 
for making critically important 
distinctions between the various schizophrenia spectrum and other psychotic disorders. 



Diagnostic Features 


The essential 
features of psychotic disorder due to another medical 
condition are prominent 
delusions or hallucinations that 
are judged to be attributable to the physiological 
effects of 
another medical 
condition and are not 
better explained by another mental 
disorder (e.g., the 
symptoms are not 
a psychologically mediated response to a severe medical 
condition, in which 
case a diagnosis of brief psychotic disorder, with marked stressor, would be appropriate). 


132 


Hallucinations can occur in any sensory modality (i.e., visual, olfactory, gustatory, tactile, or 
auditory), but 
certain etiological 
factors are likely to evoke specific hallucinatory phenomena. 
Olfactory hallucinations are suggestive of temporal 
lobe epilepsy, for example. Hallucinations 
may vary from 
simple and unformed to highly complex and organized, depending on etiological 
and environmental 
factors. Psychotic disorder due to another medical 
condition is generally not 
diagnosed if the individual 
maintains reality testing for the hallucinations and appreciates that 
they result 
from 
the medical 
condition. Delusions may have a variety of themes, including 
somatic, grandiose, religious, and, most 
commonly, persecutory. On the whole, however, 
associations between delusions and particular medical 
conditions appear to be less specific than 
is the case for hallucinations. 


Although there are no infallible guidelines to determine whether the psychotic disturbance is 
etiologically attributable to another medical 
condition, three considerations can provide some 
guidance: 
biological 
plausibility, temporality, and typicality. First, the presence of a medical 
condition that 
has the potential 
to cause psychotic symptoms through a putative physiological 
mechanism 
(e.g., severe, generalized infection; 
porphyria; 
lupus; 
temporal 
lobe epilepsy) must 
be identified (biological 
plausibility). The second consideration is whether there is a temporal 
association between the onset, exacerbation, or remission of the medical 
condition and that 
of the 
psychotic disturbance (temporality). The third consideration in favor of a medical 
etiology of the 
psychotic symptoms is the presence of features that 
would be atypical 
for an independent 
psychotic disorder (e.g., atypical 
age at 
onset, presence of visual 
or olfactory hallucinations) 
(typicality). Finally, causes of psychotic symptoms other than the physiological 
effects of a 
medical 
condition need to be considered and ruled out 
(e.g., substance/medication-induced 
psychotic disorder, psychotic symptoms occurring as side effects of the treatment 
of the medical 
condition). 


The temporal 
association of the onset 
or exacerbation of the medical 
condition offers the 
greatest 
diagnostic certainty that 
the delusions or hallucinations are attributable to a medical 
condition. Additional 
factors may include concomitant 
treatments for the underlying medical 
condition that 
confer a risk for psychosis independently, such as steroid treatment 
for 
autoimmune disorders. 


The diagnosis of psychotic disorder due to another medical 
condition depends on the clinical 
condition of each individual, and the diagnostic tests will 
vary according to that 
condition. A 
wide variety of medical 
conditions may cause psychotic symptoms. These include neurological 
conditions (e.g., neoplasms, cerebrovascular disease, Huntington s disease, Parkinson s disease, 
multiple sclerosis, epilepsy, auditory or visual 
nerve injury or impairment, deafness, migraine, 
central 
nervous system 
infections), endocrine conditions (e.g., hyper-and hypothyroidism, 



hyper-and hypoparathyroidism, hyper-and hypoadrenocorticism), metabolic conditions (e.g., 


hypoxia, hypercarbia, hypoglycemia), vitamin B12 
deficiency, fluid or electrolyte imbalances, 
hepatic or renal 
diseases, and autoimmune disorders with central 
nervous system 
involvement 
(e.g., systemic lupus erythematosus, N-methyl-D-aspartate [NMDA] receptor autoimmune 
encephalitis). The associated physical 
examination findings, laboratory findings, and patterns of 
prevalence or onset reflect the etiological medical condition. 


Prevalence 


Prevalence rates for psychotic disorder due to another medical 
condition are difficult 
to estimate 
given the wide variety of underlying medical 
etiologies. Lifetime prevalence has been estimated 
to range from 
0.21% to 0.54% in studies in Sweden and Finland. When the prevalence findings 
are stratified by age group, individuals older than 65 years have a significantly greater prevalence 
of 0.74% compared with those in younger age groups in Finland. Rates of psychosis also vary 
according to the underlying medical 
condition; 
conditions most 
commonly associated with 
psychosis include untreated endocrine and metabolic disorders, autoimmune disorders (e.g., 
systemic lupus erythematosus, NMDA receptor autoimmune encephalitis), or temporal 
lobe 
epilepsy. Psychosis attributable to epilepsy 


133 


has been further differentiated into ictal, postictal, and interictal 
psychosis. The most 
common of 
these is postictal 
psychosis, observed in 2% 7.8% of individuals with epilepsy. Among older 
individuals, there may be a higher prevalence of the disorder in women, although additional 
sex-
or gender-related features are not 
clear and vary considerably with the sex and gender 
distributions of the underlying medical 
conditions. An estimated 60% of older individuals with 
new-onset psychosis have a medical etiology for their psychotic symptoms. 


Development and Course 


Psychotic disorder due to another medical 
condition may be a single transient 
state or it 
may be 
recurrent, cycling with exacerbations and remissions of the underlying medical 
condition. 
Although treatment 
of the underlying medical 
condition often results in a resolution of the 
psychosis, this is not always the case, and psychotic symptoms may persist long after the medical 
event 
(e.g., psychotic disorder due to focal 
brain injury). In the context 
of chronic conditions 
such as multiple sclerosis or chronic interictal 
psychosis of epilepsy, the psychosis may assume a 
long-term course. 


The expression of psychotic disorder due to another medical 
condition does not 
differ 
substantially in phenomenology depending on age at 
occurrence. However, older age groups 
have a higher prevalence of the disorder, which is most 
likely due to the increasing medical 
burden associated with advanced age and the cumulative effects of deleterious exposures and 
age-related processes (e.g., atherosclerosis). The nature of the underlying medical 
conditions is 
likely to change across the lifespan, with younger age groups more affected by epilepsy, head 
trauma, autoimmune, and neoplastic diseases of early to midlife, and older age groups more 
affected by a neurodegenerative disease (e.g., Alzheimer s), stroke disease, anoxic events, and 
multiple system 
comorbidities. Underlying factors with increasing age, such as preexisting 
cognitive impairment 
as well 
as vision and hearing impairments, may incur a greater risk for 



psychosis, possibly by serving to lower the threshold for experiencing psychosis. 


Risk and Prognostic Factors 


Course 
modifiers. 
Identification and treatment 
of the underlying medical 
condition has the 
greatest 
impact 
on course, although preexisting central 
nervous system 
injury may confer a 
worse course outcome (e.g., head trauma, cerebrovascular disease). 


Association With Suicidal 
Thoughts or Behavior 


Suicide risk in the context 
of psychotic disorder due to another 
medical 
condition is not 
clearly 
delineated, although certain conditions such as epilepsy and multiple sclerosis are associated 
with increased rates of suicide, which may be further increased in the presence of psychosis. 


Functional 
Consequences of Psychotic Disorder Due to Another 
Medical 
Condition 


Functional 
disability is typically severe in the context 
of psychotic disorder due to another 
medical 
condition but 
will 
vary considerably by the type of condition and likely improve with 
successful resolution of the condition. 


Differential 
Diagnosis 


Delirium and 
major or mild 
neurocognitive 
disorder. 
Hallucinations and delusions commonly occur in 
the context of a delirium; a separate diagnosis of psychotic disorder due to 


134 


another medical 
condition is not 
given if the delusions and/or hallucinations occur exclusively 
during the course of a delirium. On the other hand, a diagnosis of psychotic disorder due to 
another medical 
condition may be given in addition to a diagnosis of major or mild 
neurocognitive disorder if the delusions or hallucinations are judged to be a physiological 
consequence of the pathological 
process causing the neurocognitive disorder (e.g., psychotic 
disorder due to Lewy body disease, with delusions). 
Substance/medication-induced 
psychotic 
disorder. 
If there is evidence of recent 
or prolonged 


substance use (including medications with psychoactive effects), withdrawal 
from 
a substance or 
medication that 
can cause psychotic symptoms on withdrawal, or exposure to a toxin (e.g., LSD 
[lysergic acid diethylamide] intoxication, alcohol 
withdrawal), a substance/medication-induced 
psychotic disorder should be considered. Symptoms that occur during or shortly after (i.e., within 
4 weeks) of substance intoxication or withdrawal 
or after medication use may be especially 
indicative of a substance-induced psychotic disorder, depending on the character, duration, or 
amount 
of the substance used. If the clinician has ascertained that 
the disturbance is due to both a 
medical 
condition and substance use, both diagnoses (i.e., psychotic disorder due to another 
medical condition and substance/medication-induced psychotic disorder) can be given. 


Psychotic 
disorder. 
Psychotic disorder due to another medical 
condition must 
be distinguished 
from 
a psychotic disorder that 
is not 
due to another medical 
condition (e.g., schizophrenia, 
delusional 
disorder, schizoaffective disorder) or a major depressive or bipolar disorder, with 
psychotic features. In psychotic disorders and in depressive or bipolar disorders, with psychotic 



features, no specific and direct 
causative physiological 
mechanisms associated with a medical 
condition can be demonstrated. Late age at 
onset 
and the absence of a personal 
or family history 
of schizophrenia or delusional disorder suggest the need for a thorough assessment to rule out the 
diagnosis of psychotic disorder due to another medical 
condition. Auditory hallucinations that 
involve voices speaking complex sentences are more characteristic of schizophrenia than of 
psychotic disorder due to a medical 
condition. While certain symptoms suggest 
a medical 
or 
toxic etiology (e.g., visual 
or olfactory hallucinations, dreamlike quality of delusions [individual 
as uninvolved observer]), there are no pathognomonic signs or symptoms that 
unequivocally 
point 
clinicians either way. Visual 
hallucinations are not 
uncommon in schizophrenia or bipolar 
disorder, and olfactory hallucinations (e.g., unpleasant 
smells) are also consistent 
with a 
diagnosis of schizophrenia. Thus, clinicians should not 
give undue weight 
to any one particular 
hallucination alone when deciding between a psychiatric and a medical 
cause for 
psychopathology. 


Comorbidity 


Psychotic disorder due to another medical 
condition in individuals older than 80 years is 
associated with concurrent 
major neurocognitive disorder (dementia). Alzheimer s disease is 
commonly accompanied by psychosis, and psychosis is a defining feature in Lewy body disease. 


Catatonia 


Catatonia can occur in the context of several disorders, including neurodevelopmental, psychotic, 
bipolar, and depressive disorders, and other medical 
conditions (e.g., cerebral 
folate deficiency, 
rare autoimmune and paraneoplastic disorders). The manual 
does not 
treat 
catatonia as an 
independent class but recognizes a) catatonia associated with another 


135 


mental 
disorder (i.e., a neurodevelopmental, psychotic disorder, a bipolar disorder, a depressive 
disorder, or other mental 
disorder), b) catatonic disorder due to another medical 
condition, and c) 
unspecified catatonia. 


Catatonia is defined by the presence of 3 or more of 12 psychomotor features in the 
diagnostic criteria for catatonia associated with another mental 
disorder and catatonic disorder 
due to another medical 
condition. The essential 
feature of catatonia is a marked psychomotor 
disturbance that 
may involve decreased motor activity, decreased engagement 
during interview 
or physical 
examination, or excessive and peculiar motor activity. The clinical 
presentation of 
catatonia can be puzzling, as the psychomotor disturbance may range from 
marked 
unresponsiveness to marked agitation. Motoric immobility may be severe (stupor) or moderate 
(catalepsy and waxy flexibility). Similarly, decreased engagement 
may be severe (mutism) or 
moderate (negativism). Excessive and peculiar motor behaviors can be complex (e.g., 
stereotypy) or simple (agitation) and may include echolalia and echopraxia. In extreme cases, the 
same individual 
may wax and wane between decreased and excessive motor activity. The 
seemingly opposing clinical 
features, variable manifestations of the diagnosis, and overemphasis 
in teaching on rare, severe signs such as waxy flexibility contribute to a lack of awareness and 



decreased recognition of catatonia. During severe stages of catatonia, the individual 
may need 
careful 
supervision to avoid self-harm 
or harming others. There are potential 
risks from 
malnutrition, exhaustion, thromboembolism, pressure ulcers, muscle contractions, hyperpyrexia 
and self-inflicted injury. 


Catatonia Associated 
With 
Another Mental 
Disorder 
(Catatonia Specifier) 


F06.1 


A. 
The 
clinical picture 
is dominated 
by three 
(or more) of 
the 
following 
symptoms: 
1. 
Stupor (i.e., 
no 
psychomotor activity; 
not 
actively relating 
to 
environment). 
2. 
Catalepsy (i.e., 
passive 
induction 
of 
a 
posture 
held 
against 
gravity). 
3. 
Waxy flexibility (i.e., 
slight, 
even 
resistance 
to 
positioning 
by examiner). 
4. 
Mutism (i.e., 
no, 
or very little, 
verbal response 
[exclude 
if 
known 
aphasia]). 
5. 
Negativism (i.e., 
opposition 
or no 
response 
to 
instructions or external stimuli). 
6. 
Posturing 
(i.e., 
spontaneous and 
active 
maintenance 
of 
a 
posture 
against 
gravity). 
7. 
Mannerism (i.e., 
odd, 
circumstantial caricature 
of 
normal actions). 
8. 
Stereotypy (i.e., 
repetitive, 
abnormally frequent, 
non-goal-directed 
movements). 
9. 
Agitation, 
not 
influenced 
by external stimuli. 
10. 
Grimacing. 
11. 
Echolalia 
(i.e., 
mimicking 
another s speech). 
12. 
Echopraxia 
(i.e., 
mimicking 
another s movements). 
Coding 
note: 
Indicate 
the 
name 
of 
the 
associated 
mental disorder when 
recording 
the 
name 
of 
the 
condition 
(i.e., 
F06.1 
catatonia 
associated 
with 
major depressive 
disorder). 
Code 
first 
the 
associated 
mental disorder (e.g., 
neurodevelopmental 
disorder, 
brief 
psychotic disorder, 
schizophreniform disorder, 
schizophrenia, 
schizoaffective 
disorder, 
bipolar disorder, 
major depressive 
disorder, 
or other mental 
disorder) (e.g., 
F25.1 
schizoaffective 
disorder, 
depressive 
type; 
F06.1 
catatonia 
associated 
with 
schizoaffective 
disorder). 


136 


Diagnostic Features 


Catatonia associated with another mental 
disorder (catatonia specifier) may be used when criteria 
are met 
for catatonia during the course of a neurodevelopmental, psychotic, bipolar, depressive, 
or other mental 
disorder. The catatonia specifier is appropriate when the clinical 
picture is 
characterized by marked psychomotor disturbance and involves at 
least 
three of the 12 diagnostic 



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in 
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neurodevel 
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Di 
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cont 



 
 
 
139 



Bipolar and Related Disorders 


Bipolar and related disorders 
are found between the chapters on schizophrenia 
spectrum 
and other psychotic disorders and depressive disorders in DSM-5-TR 
in recognition of 
their place as a bridge between those two diagnostic classes in terms of symptomatology, family 
history, and genetics. The diagnoses included in this chapter are bipolar I disorder, bipolar II 
disorder, cyclothymic disorder, substance/medication-induced bipolar and related disorder, 
bipolar and related disorder due to another medical 
condition, other specified bipolar and related 
disorder, and unspecified bipolar and related disorder. 


The bipolar I disorder criteria represent 
the modern understanding of the classic manic-
depressive disorder or affective psychosis described in the nineteenth century, differing from 
that 
classic description only to the extent 
that 
neither psychosis nor the lifetime experience of a major 
depressive episode is a requirement. However, the vast 
majority of individuals whose symptoms 
meet 
the criteria for a fully syndromal 
manic episode also experience major depressive episodes 
during the course of their lives. 


Bipolar II disorder, requiring the lifetime experience of at 
least 
one major depressive episode 
and at 
least 
one hypomanic episode (but 
no history of mania), is no longer thought 
to be a less 
severe condition than bipolar I disorder, largely because of the burden of depression in bipolar II 
disorder and because the instability of mood experienced by individuals with bipolar II disorder 
is often accompanied by serious impairment in work and social functioning. 


The diagnosis of cyclothymic disorder is given to adults who experience at 
least 
2 years (for 
children, a full 
year) of both hypomanic and depressive periods without 
ever fulfilling the criteria 
for an episode of mania, hypomania, or major depression. 


A large number of substances of abuse, some prescribed medications, and several 
medical 
conditions can be associated with manic-like phenomena. This fact 
is recognized in the 
diagnoses of substance/medication-induced bipolar and related disorder and bipolar and related 
disorder due to another medical condition. 


The recognition that 
there are individuals who experience bipolar-like phenomena with 
symptoms that 
do not 
meet 
the criteria for bipolar I, bipolar II, or cyclothymic disorder is 
reflected in the availability of the other specified bipolar and related disorder category. Specific 
criteria for a disorder involving short-duration hypomania are provided in Section III in the hope 
of encouraging further study of this presentation of bipolar disorder symptomatology and its 
course. 


Bipolar I 
Disorder 


Diagnostic Criteria 



For a 
diagnosis of 
bipolar I 
disorder, 
it 
is necessary to 
meet 
the 
following 
criteria 
for 
a 
manic episode. 
The 
manic episode 
may have 
been 
preceded 
by and 
may be 
followed 
by hypomanic or major depressive 
episodes. 


140 


Manic 
Episode 


A. 
A 
distinct 
period 
of 
abnormally and 
persistently elevated, 
expansive, 
or irritable 
mood 
and 
abnormally and 
persistently increased 
activity or energy, 
lasting 
at 
least 
1 
week and 
present 
most 
of 
the 
day, 
nearly every day (or any duration 
if 
hospitalization 
is necessary). 
B. 
During 
the 
period 
of 
mood 
disturbance 
and 
increased 
energy or activity, 
three 
(or 
more) of 
the 
following 
symptoms (four if 
the 
mood 
is only irritable) are 
present 
to 
a 
significant 
degree 
and 
represent 
a 
noticeable 
change 
from usual behavior: 
1. 
Inflated 
self-esteem or grandiosity. 
2. 
Decreased 
need 
for sleep 
(e.g., 
feels rested 
after only 3 
hours of 
sleep). 
3. 
More 
talkative 
than 
usual or pressure 
to 
keep 
talking. 
4. 
Flight 
of 
ideas or subjective 
experience 
that 
thoughts are 
racing. 
5. 
Distractibility (i.e., 
attention 
too 
easily drawn 
to 
unimportant 
or irrelevant 
external stimuli), 
as reported 
or observed. 
6. 
Increase 
in 
goal-directed 
activity (either socially, 
at 
work or school, 
or 
sexually) or psychomotor agitation 
(i.e., 
purposeless non-goal-directed 
activity). 
7. 
Excessive 
involvement 
in 
activities that 
have 
a 
high 
potential for painful 
consequences (e.g., 
engaging 
in 
unrestrained 
buying 
sprees, 
sexual 
indiscretions, 
or foolish 
business investments). 
C. 
The 
mood 
disturbance 
is sufficiently severe 
to 
cause 
marked 
impairment 
in 
social or occupational functioning 
or to 
necessitate 
hospitalization 
to 
prevent 
harm to 
self 
or others, 
or there 
are 
psychotic features. 
D. 
The 
episode 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication, 
other treatment) or another medical condition. 
Note: 
A 
full manic episode 
that 
emerges during 
antidepressant 
treatment 
(e.g., 
medication, 
electroconvulsive 
therapy) but 
persists at 
a 
fully syndromal level 
beyond 
the 
physiological effect 
of 
that 
treatment 
is sufficient 
evidence 
for a 
manic episode 
and, 
therefore, 
a 
bipolar I 
diagnosis. 


Note: 
Criteria 
A D constitute 
a 
manic episode. 
At 
least 
one 
lifetime 
manic episode 
is 
required 
for the 
diagnosis of 
bipolar I 
disorder. 


Hypomanic 
Episode 


A. 
A 
distinct 
period 
of 
abnormally and 
persistently elevated, 
expansive, 
or irritable 
mood 
and 
abnormally and 
persistently increased 
activity or energy, 
lasting 
at 
least 
4 
consecutive 
days and 
present 
most 
of 
the 
day, 
nearly every day. 

B. 
During 
the 
period 
of 
mood 
disturbance 
and 
increased 
energy and 
activity, 
three 
(or more) of 
the 
following 
symptoms (four if 
the 
mood 
is only irritable) have 
persisted, 
represent 
a 
noticeable 
change 
from usual behavior, 
and 
have 
been 
present 
to 
a 
significant 
degree: 
1. 
Inflated 
self-esteem or grandiosity. 
2. 
Decreased 
need 
for sleep 
(e.g., 
feels rested 
after only 3 
hours of 
sleep). 
3. 
More 
talkative 
than 
usual or pressure 
to 
keep 
talking. 
4. 
Flight 
of 
ideas or subjective 
experience 
that 
thoughts are 
racing. 
5. 
Distractibility (i.e., 
attention 
too 
easily drawn 
to 
unimportant 
or irrelevant 
external stimuli), 
as reported 
or observed. 
6. 
Increase 
in 
goal-directed 
activity (either socially, 
at 
work or school, 
or 
sexually) or psychomotor agitation. 
7. 
Excessive 
involvement 
in 
activities that 
have 
a 
high 
potential for painful 
consequences (e.g., 
engaging 
in 
unrestrained 
buying 
sprees, 
sexual 
indiscretions, 
or foolish 
business investments). 
141 


C. 
The 
episode 
is associated 
with 
an 
unequivocal change 
in 
functioning 
that 
is 
uncharacteristic of 
the 
individual when 
not 
symptomatic. 
D. 
The 
disturbance 
in 
mood 
and 
the 
change 
in 
functioning 
are 
observable 
by 
others. 
E. 
The 
episode 
is not 
severe 
enough 
to 
cause 
marked 
impairment 
in 
social or 
occupational functioning 
or to 
necessitate 
hospitalization. 
If 
there 
are 
psychotic 
features, 
the 
episode 
is, 
by definition, 
manic. 
F. 
The 
episode 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication, 
other treatment) or another medical condition. 
Note: 
A 
full hypomanic episode 
that 
emerges during 
antidepressant 
treatment 
(e.g., 
medication, 
electroconvulsive 
therapy) but 
persists at 
a 
fully syndromal 
level beyond 
the 
physiological effect 
of 
that 
treatment 
is sufficient 
evidence 
for a 
hypomanic episode 
diagnosis. 
However, 
caution 
is indicated 
so 
that 
one 
or two 
symptoms (particularly increased 
irritability, 
edginess, 
or agitation 
following 
antidepressant 
use) are 
not 
taken 
as sufficient 
for diagnosis of 
a 
hypomanic 
episode, 
nor necessarily indicative 
of 
a 
bipolar diathesis. 


Note: 
Criteria 
A F 
constitute 
a 
hypomanic episode. 
Hypomanic episodes are 
common 
in 
bipolar I 
disorder but 
are 
not 
required 
for the 
diagnosis of 
bipolar I 
disorder. 


Major Depressive 
Episode 


A. 
Five 
(or more) of 
the 
following 
symptoms have 
been 
present 
during 
the 
same 
2week 
period 
and 
represent 
a 
change 
from previous functioning; 
at 
least 
one 
of 
the 
symptoms is either (1) depressed 
mood 
or (2) loss of 
interest 
or pleasure. 

Note: 
Do 
not 
include 
symptoms that 
are 
clearly attributable 
to 
another medical 
condition. 


1. 
Depressed 
mood 
most 
of 
the 
day, 
nearly every day, 
as indicated 
by either 
subjective 
report 
(e.g., 
feels sad, 
empty, 
or hopeless) or observation 
made 
by 
others (e.g., 
appears tearful). 
(Note: 
In 
children 
and 
adolescents, 
can 
be 
irritable 
mood.) 
2. 
Markedly diminished 
interest 
or pleasure 
in 
all, 
or almost 
all, 
activities most 
of 
the 
day, 
nearly every day (as indicated 
by either subjective 
account 
or 
observation). 
3. 
Significant 
weight 
loss when 
not 
dieting 
or weight 
gain 
(e.g., 
a 
change 
of 
more 
than 
5% of 
body weight 
in 
a 
month), 
or decrease 
or increase 
in 
appetite 
nearly every day. 
(Note: 
In 
children, 
consider failure 
to 
make 
expected 
weight 
gain.) 
4. 
Insomnia 
or hypersomnia 
nearly every day. 
5. 
Psychomotor agitation 
or retardation 
nearly every day (observable 
by others, 
not 
merely subjective 
feelings of 
restlessness or being 
slowed 
down). 
6. 
Fatigue 
or loss of 
energy nearly every day. 
7. 
Feelings of 
worthlessness or excessive 
or inappropriate 
guilt 
(which 
may be 
delusional) nearly every day (not 
merely self-reproach 
or guilt 
about 
being 
sick). 
8. 
Diminished 
ability to 
think or concentrate, 
or indecisiveness, 
nearly every day 
(either by subjective 
account 
or as observed 
by others). 
9. 
Recurrent 
thoughts of 
death 
(not 
just 
fear of 
dying), 
recurrent 
suicidal ideation 
without 
a 
specific plan, 
or a 
suicide 
attempt 
or a 
specific plan 
for committing 
suicide. 
B. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
C. 
The 
episode 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
or 
another medical condition. 
Note: 
Criteria 
A C constitute 
a 
major depressive 
episode. 
Major depressive 
episodes are 
common 
in 
bipolar I 
disorder but 
are 
not 
required 
for the 
diagnosis of 
bipolar I 
disorder. 


142 


Note: 
Responses to 
a 
significant 
loss (e.g., 
bereavement, 
financial ruin, 
losses from 
a 
natural disaster, 
a 
serious medical illness or disability) may include 
the 
feelings of 
intense 
sadness, 
rumination 
about 
the 
loss, 
insomnia, 
poor appetite, 
and 
weight 
loss 
noted 
in 
Criterion 
A, 
which 
may resemble 
a 
depressive 
episode. 
Although 
such 
symptoms may be 
understandable 
or considered 
appropriate 
to 
the 
loss, 
the 
presence 
of 
a 
major depressive 
episode 
in 
addition 
to 
the 
normal response 
to 
a 
significant 
loss should 
also 
be 
carefully considered. 
This decision 
inevitably requires 



the 
exercise 
of 
clinical judgment 
based 
on 
the 
individual s history and 
the 
cultural 
norms for the 
expression 
of 
distress in 
the 
context 
of 
loss.1 


Bipolar I 
Disorder 


A. 
Criteria 
have 
been 
met 
for at 
least 
one 
manic episode 
(Criteria 
A D under 
 Manic Episode  above). 
B. 
At 
least 
one 
manic episode 
is not 
better explained 
by schizoaffective 
disorder 
and 
is not 
superimposed 
on 
schizophrenia, 
schizophreniform disorder, 
delusional disorder, 
or other specified 
or unspecified 
schizophrenia 
spectrum 
and 
other psychotic disorder. 
Coding 
and 
Recording 
Procedures 


The 
diagnostic code 
for bipolar I 
disorder is based 
on 
type 
of 
current 
or most 
recent 
episode 
and 
its status with 
respect 
to 
current 
severity, 
presence 
of 
psychotic 
features, 
and 
remission 
status. 
Current 
severity and 
psychotic features are 
only 
indicated 
if 
full criteria 
are 
currently met 
for a 
manic or major depressive 
episode. 
Remission 
specifiers are 
only indicated 
if 
the 
full criteria 
are 
not 
currently met 
for a 
manic, 
hypomanic, 
or major depressive 
episode. 
Codes are 
as follows: 


Bipolar I 
disorder 
Current or 
most 
recent 
episode 
manic 
Current or 
most recent 
episode 
hypomanic* 
Current or 
most 
recent 
episode 
depressed 
Current or 
most recent 
episode 
unspecified** 
Mild 
(p. 
175) 
Moderate 
(p. 
175) 
Severe 
(p. 
175) 
F31.11 
F31.12 
F31.13 
NA 
NA 
NA 
F31.31 
F31.32 
F31.4 
NA 
NA 
NA 
143 
F31.2 
NA 
F31.5 
NA 
With 
psychotic features*** 
(p. 
173) 
In 
partial remission 
(p. 
175) 
In 
full remission 
(p. 
175) 
Unspecified 
F31.73 
F31.74 
F31.9 
F31.71 
F31.72 
F31.9 
F31.75 
F31.76 
F31.9 
NA 
NA 
NA 


*Severity and psychotic specifiers do not apply; code F31.0 for cases not in remission. 
**Severity, psychotic, and remission specifiers do not apply. Code F31.9. 
***If psychotic features are present, code the  with psychotic features  specifier irrespective of episode severity. 


In 
recording 
the 
name 
of 
a 
diagnosis, 
terms should 
be 
listed 
in 
the 
following 
order: 
bipolar I 
disorder, 
type 
of 
current 
episode 
(or most 
recent 
episode 
if 
bipolar I 
disorder is in 
partial or full remission), 
severity/psychotic/remission 
specifiers, 
followed 
by as many of 
the 
following 
specifiers without 
codes as apply to 
the 
current 
episode 
(or the 
most 
recent 
episode 
if 
bipolar I 
disorder is in 
partial or full 
remission). 
Note: 
The 
specifiers  with 
rapid 
cycling  and 
 with 
seasonal pattern  
describe 
the 
pattern 
of 
mood 
episodes. 



Specify 
if: 


With 
anxious 
distress 
(pp. 
169 170) 


With 
mixed 
features 
(pp. 
170 171) 


With 
rapid 
cycling 
(p. 
171) 


With 
melancholic 
features 
(pp. 
171 172) 


With 
atypical 
features 
(pp. 
172 173) 


With 
mood-congruent psychotic 
features 
(p. 
173; 
applies to 
manic episode 


and/or major depressive 
episode) 


With 
mood-incongruent psychotic 
features 
(p. 
173; 
applies to 
manic episode 
and/or major depressive 
episode) 
With 
catatonia 
(p. 
173). 
Coding 
note: 
Use 
additional code 
F06.1. 
With 
peripartum onset 
(pp. 
173 174) 
With 
seasonal 
pattern 
(pp. 
174 175) 


Diagnostic Features 


Bipolar I disorder is characterized by a clinical 
course of recurring mood episodes (manic, 
depressive, and hypomanic), but 
the occurrence of at 
least 
one manic episode is necessary for the 
diagnosis of bipolar I disorder. The essential 
feature of a manic episode is a distinct 
period 
during which there is an abnormally, persistently elevated, expansive, or irritable mood and 
persistently increased activity or energy that 
is present 
for most 
of the day, nearly every day, for 
a period of at 
least 
1 week (or any duration if hospitalization is necessary), accompanied by at 
least 
three additional 
symptoms from 
Criterion B. If the mood is irritable rather than elevated or 
expansive, at least four Criterion B symptoms must be present. 


Mood in a manic episode is often described as euphoric, excessively cheerful, high, or 
 feeling on top of the world.  In some cases, the mood is of such a highly infectious quality that 
it is easily recognized as excessive and may be characterized by unlimited and 


144 


haphazard enthusiasm 
for interpersonal, sexual, or occupational 
interactions. For example, 
the individual 
may spontaneously start 
extensive conversations with strangers in public. Often 
the predominant 
mood is irritable rather than elevated, particularly when the individual s wishes 
are denied or if the individual 
has been using substances. Rapid shifts in mood over brief periods 
of time may occur and are referred to as lability (i.e., the alternation among euphoria, dysphoria, 
and irritability). In children, happiness, silliness, and  goofiness  are normal 
in many social 
contexts; 
however, if these symptoms are recurrent, inappropriate to the context, and beyond 
what 
is expected for the developmental 
level 
of the child, they may meet 
the Criterion A mood 
requirement 
of abnormally elevated mood. For the happiness or silliness of a child to meet 
Criterion A, it 
must 
be distinctly increased from 
the child s baseline and accompanied by 
persistently increased activity or energy levels that 
to those who know the child well 
are clearly 
unusual 
for that 
child. For a child s symptoms to meet 
criteria for a manic episode, the symptoms 



must 
also meet 
Criterion B 
for mania and must 
also represent 
a change from 
the child s usual 
baseline. 


During the manic episode, the individual 
may engage in multiple overlapping new projects. 
The projects are often initiated with little knowledge of the topic, and nothing seems out 
of the 
individual s reach. The increased activity or energy levels may manifest 
at 
unusual 
hours of the 
day, such as during the individual s normal sleep phase. 


Inflated self-esteem 
is typically present, ranging from 
uncritical 
self-confidence to marked 
grandiosity, and may reach delusional 
proportions (Criterion B1). Despite lack of any particular 
experience or talent, the individual 
may embark on complex tasks such as writing a novel 
or 
seeking publicity for some impractical 
invention. Grandiose delusions (e.g., of having a special 
relationship to a famous person) are common. In children, overestimation of abilities and belief 
that, for example, they are the best 
at 
a sport 
or the smartest 
in the class is normal; 
however, 
when such beliefs are present 
despite clear evidence to the contrary or the child attempts feats 
that 
are clearly dangerous and, most 
important, represent 
a change from 
the child s normal 
behavior, the grandiosity criterion should be considered satisfied. 


One of the most 
common features is a decreased need for sleep (Criterion B2), which is 
distinct 
from 
insomnia (during which the individual 
wants to sleep or feels the need to sleep but 
is unable to). The individual 
may sleep little, if at 
all, or may awaken several 
hours earlier than 
usual, feeling rested and full 
of energy. When the sleep disturbance is severe, the individual 
may 
go for days without 
sleep, yet 
not 
feel 
tired. Often decreased need for sleep heralds the onset 
of a 
manic episode. 


Speech can be rapid, pressured, loud, and difficult 
to interrupt 
(Criterion B3). Individuals 
may talk continuously and without 
regard for others  wishes to communicate, often in an 
intrusive manner or without 
concern for the relevance of what 
is said. Speech is sometimes 
characterized by jokes, puns, amusing irrelevancies, and theatricality, with dramatic mannerisms, 
singing, and excessive gesturing. Loudness and forcefulness of speech often become more 
important 
than what 
is conveyed. If the individual s mood is more irritable than expansive, 
speech may be marked by complaints, hostile comments, or angry tirades, particularly if attempts 
are made to interrupt 
the individual. Both Criterion A and Criterion B 
symptoms may be 
accompanied by symptoms of the opposite (i.e., depressive) pole (see  with mixed features  
specifier, pp. 170 171). 


Often the individual s thoughts race at 
a rate faster than can be expressed through speech 
(Criterion B4). Frequently there is flight 
of ideas evidenced by a nearly continuous flow of 
accelerated speech, with abrupt 
shifts from 
one topic to another. When flight 
of ideas is severe, 
speech may become disorganized, incoherent, and particularly distressing to the individual. 
Sometimes thoughts are experienced as so crowded that it is very difficult to speak. 


Distractibility (Criterion B5) is evidenced by an inability to censor immaterial 
external 
stimuli 
(e.g., the interviewer s attire, background noises or conversations, furnishings in the 
room) and often prevents individuals experiencing mania from 
holding a rational 
conversation or 
attending to instructions. 


145 


The increase in goal-directed activity (Criterion B6) often consists of excessive planning and 
participation in multiple activities, including sexual, occupational, political, or religious 



activities. Increased sexual 
drive, fantasies, and behavior are often present. Individuals in a 
manic episode usually show increased sociability (e.g., renewing old acquaintances or calling or 
contacting friends or even strangers), without 
regard to the intrusive, domineering, and 
demanding nature of these interactions. They often also display psychomotor agitation or 
restlessness (i.e., purposeless activity) by pacing or by holding multiple conversations 
simultaneously. Some individuals write excessive letters, e-mails, text 
messages, and so forth, on 
many different topics to friends, public figures, or the media. 


The increased activity criterion can be difficult 
to ascertain in children; 
however, when the 
child takes on many tasks simultaneously, starts devising elaborate and unrealistic plans for 
projects, develops previously absent 
and developmentally inappropriate sexual 
preoccupations 
(not 
accounted for by sexual 
abuse or exposure to sexually explicit 
material), then Criterion B 
might 
be met 
based on clinical 
judgment. It 
is essential 
to determine whether the behavior 
represents a change from 
the child s baseline behavior; 
occurs most 
of the day, nearly every day 
for the requisite time period; and occurs in temporal association with other symptoms of mania. 


The expansive mood, excessive optimism, grandiosity, and poor judgment 
often lead to 
reckless involvement 
in activities such as spending sprees, giving away possessions, reckless 
driving, foolish business investments, and sexual indiscretions that are unusual for the individual, 
even though these activities are likely to have catastrophic consequences (Criterion B7). The 
individual 
may purchase many unneeded items without 
the money to pay for them 
and, in some 
cases, give them 
away. Sexual 
indiscretions may include infidelity or indiscriminate sexual 
encounters with strangers, often disregarding the risk of sexually transmitted diseases or 
interpersonal consequences. 


The manic episode must 
result 
in marked impairment 
in social 
or occupational 
functioning 
(e.g., financial 
losses, loss of employment, school 
failure, divorce) or require hospitalization to 
prevent 
harm 
to self or others (e.g., physical 
exhaustion or hyperthermia from 
manic excitement, 
self-injurious behavior). By definition, the presence of psychotic features during a manic episode 
also satisfies Criterion C. 


Manic symptoms or syndromes that 
are attributable to the direct 
physiological 
effects of a 
drug of abuse (e.g., in the context 
of cocaine or amphetamine intoxication), the side effects of 
medications or treatments (e.g., steroids, L-dopa, antidepressants, stimulants), or another medical 
condition do not 
count 
toward the diagnosis of bipolar I disorder. However, a fully syndromal 
manic episode that 
arises during treatment 
(e.g., with medications, electroconvulsive therapy, 
light 
therapy) and persists beyond the physiological 
effect 
of the inducing agent 
(e.g., after a 
medication is fully out 
of the individual s system 
or the effects of electroconvulsive therapy 
would be expected to have dissipated completely) is sufficient 
evidence for a manic episode that 
is considered due to bipolar I disorder (Criterion D). Caution is indicated so that 
one or two 
symptoms (particularly increased irritability, edginess, or agitation following antidepressant 
use) 
are not 
taken as sufficient 
for diagnosis of a manic or hypomanic episode, nor necessarily an 
indication of a bipolar disorder diathesis. Although not 
essential 
to a diagnosis of bipolar I 
disorder, hypomanic or depressive episodes often precede or follow a manic episode. Full 
descriptions of the diagnostic features of a hypomanic episode may be found within the text 
for 
bipolar II disorder, and the features of a major depressive episode are described within the text 
for major depressive disorder. 



Associated Features 


During a manic episode, individuals often do not 
perceive that 
they are ill 
or in need of treatment 
and vehemently resist 
efforts to be treated. Individuals may change their dress, makeup, or 
personal 
appearance to a more sexually suggestive or flamboyant 
style. Some perceive a sharper 
sense of smell, hearing, or vision. Gambling and antisocial behaviors 


146 


may accompany the manic episode. Mood may shift 
very rapidly to anger or depression; 
some 
individuals may become hostile and physically threatening to others and, when delusional, 
become physically assaultive or suicidal. Serious consequences of a manic episode (e.g., 
involuntary hospitalization, difficulties with the law, serious financial 
difficulties) often result 
from 
poor judgment, loss of insight, and hyperactivity. Depressive symptoms occur in some 35% 
of manic episodes (see  with mixed features  specifier, p. 170), and mixed features are 
associated with poorer outcome and increased suicide attempts. Bipolar I disorder is also 
associated with significant decrements in quality of life and well-being. 


Trait-like features associated with the diagnosis include hyperthymic, depressive, 
cyclothymic, anxious, and irritable temperaments, sleep and circadian rhythm 
disturbances, 
reward sensitivity, and creativity. Having a first-degree relative with bipolar disorder increases 
the risk of diagnosis approximately 10-fold. 


Prevalence 


The 12-month prevalence of DSM-5 bipolar I disorder in a nationally representative U.S. adult 
sample was 1.5% and did not 
differ between men (1.6%) and women (1.5%). Compared with 
non-Hispanic Whites, prevalence of bipolar I disorder appears to be higher among Native 
Americans and lower among African Americans, Hispanics, and Asians/Pacific Islanders. 
Twelve-month prevalence of DSM-IV bipolar I disorder across 11 countries ranged from 0.0% to 
0.6% and was greater in high-income countries than in low- and middle-income countries, except 
in Japan, where prevalence was low (0.01%). The lifetime prevalence ratio in men to women is 
approximately 1.1:1. 


Development and Course 


The peak age at 
onset 
of bipolar I disorder across studies is between 20 and 30 years, but 
onset 
occurs throughout 
the life cycle. In the United States, mean age at 
onset 
of DSM-5 bipolar I 
disorder is 22 years and slightly younger for women (21.5 years) than for men (23.0 years). In a 
comparison of six international 
sites, median age at 
onset 
of DSM-IV-TR 
bipolar I disorder was 


24.3 years. Special 
considerations are necessary to apply the diagnosis in children. Because 
children of the same chronological 
age may be at 
different 
developmental 
stages, it 
is difficult 
to 
define with precision what 
is  normal  or  expected  at 
any given point. Therefore, each child 
should be judged according to his or her own baseline in determining whether a particular 
behavior is  normal  or evidence of a manic episode. Although age at 
first 
onset 
may occur in 
the 60s or 70s, onset 
of manic symptoms (e.g., sexual 
or social 
disinhibition) in late mid-life or 
late-life should prompt 
consideration of medical 
conditions (e.g., frontotemporal 
neurocognitive 
disorder) and of substance ingestion or withdrawal. 

More than 90% of individuals who have a single manic episode go on to have recurrent mood 
episodes. Approximately 60% of manic episodes occur immediately before a major depressive 
episode. Individuals with bipolar I disorder who have multiple (four or more) mood episodes 
(major depressive, manic, or hypomanic) occurring in the prior 12 months receive the specifier 
 with rapid cycling,  a common variant 
associated with poorer outcomes. About 
half of 
individuals diagnosed with bipolar disorder exhibit 
a predominant 
polarity (relapse tending to be 
either depressive or manic), with one international 
study of bipolar I disorder finding 31.3% with 
predominant 
mania, 21.4% with predominant 
depression, and 47.3% without 
polarity 
predominance. 


The course of bipolar I disorder is highly heterogeneous. Some patterns have been noted 
across episodes (e.g., a manic episode with psychotic features may be associated with psychotic 
features in subsequent 
manic episodes). Polarity of first 
episode tends to be associated with 
predominant 
polarity of future episodes and clinical 
features (e.g., depressive onset 
is associated 
with greater density of depressive episodes and suicidal behavior). The 


147 


presence of mixed features in a manic episode is associated with a poorer prognosis, poorer 
lithium response, and suicidal behavior. 


Risk and Prognostic Factors 


Environmental. 
Childhood adversity (including early emotional 
trauma, parental 
psychopathology, and family conflict) is a known risk factor for bipolar disorder and appears to 
predispose to early onset 
of bipolar disorder. Childhood adversity is also associated with poorer 
prognosis and a worse clinical 
picture that 
may include medical 
or psychiatric comorbidities, 
suicide, and associated psychotic features. More proximally, recent 
life stress and other negative 
life events increase depressive relapse risk in individuals diagnosed with bipolar disorder, 
whereas manic relapse appears to be specifically linked to goal-attainment 
life events (e.g., 
getting married, completing a degree). Cannabis and other substance use is associated with 
exacerbation of manic symptoms among individuals diagnosed with bipolar disorder, as well 
as 
first 
onset 
of manic symptoms in the general 
population. There is some evidence that 
becoming 
married is less common among individuals with bipolar disorder than in the general 
population 
and that 
a diagnosis of bipolar disorder is associated with being previously as opposed to 
currently married. 


Genetic 
and 
physiological. 
Genetic processes strongly affect 
predisposition to bipolar disorder, 
with heritability estimates around 90% in some twin studies. Risk of bipolar disorder in the 
general 
population is around 1%, while risk in a first-degree relative is 5% 10%. However, 
monozygotic concordance rates are significantly less than 100% (40% 70%), indicating that 
much risk is left 
unexplained by genes alone. The mechanism 
of heritability is not 
Mendelian, 
and involves multiple genes (or more complex genetic mechanisms) of small 
effect, interacting 
with each other, the environment, and random 
factors. Emerging genetic findings suggest 
that 
mania- and depression-proneness are inherited separately, and bipolar disorder shares a genetic 
origin with schizophrenia. 



Culture-Related Diagnostic Issues 


Bipolar I disorder symptoms tend to be consistent 
across cultural 
contexts, but 
some variation 
exists in symptom 
expression and interpretation. For example, individuals from 
different 
cultural 
backgrounds with bipolar I disorder, with psychotic features, may vary in the prevalence of flight 
of ideas or types of delusions (e.g., grandiose, persecutory, sexual, religious, or somatic). 
Cultural 
factors may affect 
disorder prevalence. For example, countries with reward-oriented 
cultural 
values that 
place significance on individual 
pursuit 
of reward have a relatively higher 
prevalence of bipolar disorder. In the United States, individuals with bipolar disorder had an 
earlier age at 
onset 
than those in Europe and were more likely to have a family history of 
psychiatric disorder. 


Culture also influences clinician diagnostic practices regarding bipolar disorder. Compared 
with non-Latinx Whites in the United States, African Americans with bipolar I disorder are at 
higher risk of being misdiagnosed with schizophrenia. Possible reasons include underrecognition 
of mood symptoms, cultural 
and linguistic misunderstanding between clinicians and the 
individuals presenting for treatment 
(e.g., misinterpretation of cultural 
mistrust 
as paranoia), 
more florid psychotic symptoms at 
presentation due to delay in receiving services, and diagnoses 
based on shorter clinical 
assessments. These factors may result 
in discriminatory misdiagnosis of 
schizophrenia, particularly in African Americans with mood disorders who present 
with 
psychotic features. 


Sex- and Gender-Related Diagnostic Issues 


Women may be more likely to experience rapid cycling and mixed states, and to have patterns of 
comorbidity that differ from those of men, including higher rates of lifetime eating 


148 


disorders. Women with bipolar I or II disorder are more likely to experience depressive 
symptoms than are men. They also have a higher lifetime risk of alcohol 
use disorder than do 
men and a much greater likelihood of alcohol 
use disorder than do women in the general 
population. 


Some women with bipolar disorder experience exacerbation of mood symptoms during the 
premenstrual 
time period, and this has been associated with a worse course of illness. Many 
women with bipolar disorder also report 
severe emotional 
disturbances during perimenopause 
when estrogen levels are decreasing. There does not 
appear to be an increased risk of mood 
episodes in pregnant 
women with bipolar disorder except 
in those who discontinue medications 
for pregnancy. In contrast, there is strong and consistent 
evidence for an increased risk of mood 
episodes (both depression and mania) in women with bipolar I disorder in the postpartum 
period. 
The specifier  with peripartum 
onset  should be used for mood episodes that 
begin during 
pregnancy or within 4 weeks of delivery.  Postpartum 
psychosis  typically resembles a manic or 
mixed mood episode with psychotic symptoms and is strongly associated with bipolar I disorder. 


Association With Suicidal 
Thoughts or Behavior 


The lifetime risk of suicide in individuals with bipolar disorder is estimated to be 20- to 30-fold 
greater than in the general population. An estimated 5% 6% of individuals with bipolar disorders 



die by suicide. While suicide attempts are higher in women, lethal 
suicide is more common in 
men with bipolar disorder. A past 
history of suicide attempt 
and percent 
days spent 
depressed in 
the past 
year are associated with greater risk of suicide attempts or completions. Nearly half of 
individuals whose symptoms meet 
criteria for bipolar disorder have an alcohol 
use disorder, and 
those with both disorders are at greater risk for suicide attempt and suicide death. 


Functional 
Consequences of Bipolar I 
Disorder 


Approximately 30% of individuals with bipolar disorder show severe impairment 
in work role 
functioning, although many individuals return to a fully functional 
level 
between episodes. 
Functional 
recovery lags substantially behind recovery from 
symptoms, especially with respect 
to occupational 
recovery, resulting in lower socioeconomic status despite equivalent 
levels of 
education when compared with the general 
population. Cognitive impairments persist 
through 
the lifespan, even during euthymic periods, and may contribute to vocational 
and interpersonal 
difficulties. Higher level of self-perceived stigma is associated with lower level of functioning. 


Differential 
Diagnosis 


Major depressive 
disorder. 
There is a risk of misdiagnosing bipolar I disorder as unipolar 
depression because of the prominence of depression in the presentation of bipolar I disorder: 
1) 
the first 
episode of bipolar disorder is often depressive, 2) depressive symptoms are the most 
frequent 
symptoms experienced across the long-term 
course of bipolar I disorder, and 3) the 
problem 
for which individuals typically seek help is depression. When the individual 
presents in 
an episode of major depression, it 
is therefore important 
to actively probe for a history of mania 
or hypomania. Factors that 
might 
indicate that 
the diagnosis is bipolar I disorder rather than 
major depressive disorder in an individual 
presenting with a current 
depressive episode include 
family history of bipolar disorder, onset 
of illness in early 20s, numerous past 
episodes, presence 
of psychotic symptoms, and a history of lack of response to antidepressant 
treatment 
or the 
emergence of a manic episode during antidepressant 
treatment 
(e.g., medication, 
electroconvulsive therapy). 


Other bipolar disorders. 
Bipolar II disorder, cyclothymic disorder, and other specified bipolar and 
related disorder are similar to bipolar I disorder by virtue of their including 


149 


periods of hypomanic symptoms in their presentations but 
are differentiated from 
bipolar I 
disorder by the absence of any manic episodes. 


Generalized 
anxiety 
disorder, 
panic 
disorder, 
posttraumatic 
stress 
disorder, 
or other anxiety 


A 


disorders. 


careful 
history of symptoms is needed to differentiate generalized anxiety disorder from 
bipolar 
disorder, as anxious ruminations may be mistaken for racing thoughts (and vice versa), and 
efforts to minimize anxious feelings may be taken as impulsive behavior. Similarly, symptoms of 
posttraumatic stress disorder need to be differentiated from 
bipolar disorder. It 
is helpful 
to 
assess the episodic nature of the 
symptoms described (classical 
bipolar I is episodic), as well 
as 
to consider symptom triggers, in making this differential diagnosis. 
Bipolar and 
related 
disorder due 
to 
another medical 
condition. 
The diagnosis of bipolar and related 



disorder due to another medical 
condition should be made instead of bipolar I disorder if the 
manic episodes are judged, based on history, laboratory findings, or physical 
examination, to be 
the direct 
physiological 
consequence of another medical 
condition (e.g., Cushing s disease, 
multiple sclerosis). 
Substance/medication-induced 
bipolar and 
related 
disorder. 
A substance/medication-induced bipolar 


and related disorder is distinguished from 
bipolar I disorder by the fact 
that 
a substance (e.g., 
stimulants, phencyclidine) or medication (e.g., steroids) is judged to be etiologically related to 
the manic episode. Because individuals with a manic episode have a tendency to overuse 
substances during an episode, it 
is important 
to determine whether the substance use is a 
consequence of a primary manic episode or whether the manic-like episode has been caused by 
the substance use. In some cases, a definitive diagnosis may involve establishing that 
the manic 
symptoms remain once the individual 
is no longer using the substance. Note that 
manic episodes 
emerging in the context 
of treatment 
with an antidepressant 
medication but 
that 
persist 
at 
a fully 
syndromal 
level 
beyond the physiological 
effect 
of the medication warrant 
a diagnosis of bipolar 
I disorder rather than substance/medication-induced bipolar and related disorder. 


Schizoaffective 
disorder. 
Schizoaffective disorder is characterized by periods in which manic and 
major depressive episodes are concurrent 
with the active phase symptoms of schizophrenia and 
periods in which delusions or hallucinations occur for at 
least 
2 weeks in the absence of a manic 
or major depressive episode. The diagnosis is  bipolar I disorder, with psychotic features  if the 
psychotic symptoms have occurred exclusively during manic and major depressive episodes. 


Attention-deficit/hyperactivity 
disorder. 
Attention-deficit/hyperactivity disorder is characterized by 
persistent 
symptoms of inattention, hyperactivity, and impulsivity, which may resemble the 
symptoms of a manic episode (e.g., distractibility, increased activity, impulsive behavior) and 
have their onset 
by age 12. In contrast, the symptoms of mania in bipolar I disorder occur in 
distinct episodes and typically begin in late adolescence or early adulthood. 


Disruptive 
mood 
dysregulation 
disorder. 
In individuals with severe irritability, particularly children 
and adolescents, care must 
be taken to apply the diagnosis of bipolar I disorder only to those who 
have had a clear episode of mania or hypomania that 
is, a distinct 
time period, of the required 
duration, during which the irritability was clearly different 
from 
the individual s baseline and 
was accompanied by the onset 
of the other characteristic symptoms of mania (e.g., grandiosity, 
decreased need for sleep, pressured speech, involvement 
in activities with a high potential 
for 
painful 
consequences). When a child s irritability is persistent 
and particularly severe, the 
diagnosis of disruptive mood dysregulation disorder would be more appropriate. Indeed, when 
any child is being assessed for mania, it 
is essential 
that 
the symptoms represent 
a clear change 
from the child s typical behavior. 


150 


Personality 
disorders. 
Personality disorders such as borderline personality disorder may have 
substantial 
symptomatic overlap with bipolar I disorder, since mood lability and impulsivity are 
common in both conditions. In order to make a diagnosis of bipolar I disorder, symptoms of 
mood lability and impulsivity must 
represent 
a distinct 
episode of illness, or there must 
be a 
noticeable increase in these symptoms over the individual s baseline in order to justify an 
additional diagnosis of bipolar I disorder. 



Comorbidity 


Co-occurring mental 
disorders are the norm 
in bipolar I disorder, with the majority of individuals 
having a history of three or more disorders. The most 
frequently comorbid disorders are anxiety 
disorders, alcohol 
use disorder, other substance use disorder, and attention-deficit/hyperactivity 
disorder. Sociocultural 
factors influence the pattern of comorbid conditions in bipolar disorder. 
For example, countries with cultural 
prohibitions against 
alcohol 
or other substance use may 
have a lower prevalence of substance use comorbidity. Bipolar I disorder is frequently associated 
with borderline, schizotypal, and antisocial 
personality disorder. In particular, although the 
underlying nature of the relationship between bipolar I disorder and borderline personality 
disorder is unclear, the substantial 
comorbidity between the two may reflect 
similarities in 
phenomenology (i.e., misdiagnosing the emotional 
extremes of borderline personality disorder as 
bipolar I disorder), the influence of borderline personality features on vulnerability to bipolar I 
disorder, and the impact 
of early childhood adversity on the development 
of both bipolar I and 
borderline personality disorder. 


Individuals with bipolar I disorder also have high rates of serious co-occurring and often 
untreated medical 
conditions, which largely explain the shortened life expectancy of those with 
bipolar disorder. Comorbidities appear in multiple organ systems, with cardiovascular and 
autoimmune diseases, obstructive sleep apnea, metabolic syndrome, and migraine more common 
among individuals with bipolar disorder than in the general 
population. Comorbid 
overweight/obesity is a particular concern for individuals with bipolar disorder and is associated 
with poor treatment outcomes. 


Bipolar II 
Disorder 


Diagnostic Criteria 
F31.81 


For a 
diagnosis of 
bipolar II 
disorder, 
it 
is necessary to 
meet 
the 
following 
criteria 
for 
a 
current 
or past 
hypomanic episode 
and 
the 
following 
criteria 
for a 
current 
or past 
major depressive 
episode: 


Hypomanic 
Episode 


A. 
A 
distinct 
period 
of 
abnormally and 
persistently elevated, 
expansive, 
or irritable 
mood 
and 
abnormally and 
persistently increased 
activity or energy, 
lasting 
at 
least 
4 
consecutive 
days and 
present 
most 
of 
the 
day, 
nearly every day. 
B. 
During 
the 
period 
of 
mood 
disturbance 
and 
increased 
energy and 
activity, 
three 
(or more) of 
the 
following 
symptoms have 
persisted 
(four if 
the 
mood 
is only 
irritable), 
represent 
a 
noticeable 
change 
from usual behavior, 
and 
have 
been 
present 
to 
a 
significant 
degree: 
1. 
Inflated 
self-esteem or grandiosity. 
2. 
Decreased 
need 
for sleep 
(e.g., 
feels rested 
after only 3 
hours of 
sleep). 
3. 
More 
talkative 
than 
usual or pressure 
to 
keep 
talking. 
4. 
Flight 
of 
ideas or subjective 
experience 
that 
thoughts are 
racing. 

151 


5. 
Distractibility (i.e., 
attention 
too 
easily drawn 
to 
unimportant 
or irrelevant 
external stimuli), 
as reported 
or observed. 
6. 
Increase 
in 
goal-directed 
activity (either socially, 
at 
work or school, 
or 
sexually) or psychomotor agitation. 
7. 
Excessive 
involvement 
in 
activities that 
have 
a 
high 
potential for painful 
consequences (e.g., 
engaging 
in 
unrestrained 
buying 
sprees, 
sexual 
indiscretions, 
or foolish 
business investments). 
C. 
The 
episode 
is associated 
with 
an 
unequivocal change 
in 
functioning 
that 
is 
uncharacteristic of 
the 
individual when 
not 
symptomatic. 
D. 
The 
disturbance 
in 
mood 
and 
the 
change 
in 
functioning 
are 
observable 
by 
others. 
E. 
The 
episode 
is not 
severe 
enough 
to 
cause 
marked 
impairment 
in 
social or 
occupational functioning 
or to 
necessitate 
hospitalization. 
If 
there 
are 
psychotic 
features, 
the 
episode 
is, 
by definition, 
manic. 
F. 
The 
episode 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication, 
other treatment) or another medical condition. 
Note: 
A 
full hypomanic episode 
that 
emerges during 
antidepressant 
treatment 
(e.g., 
medication, 
electroconvulsive 
therapy) but 
persists at 
a 
fully syndromal 
level beyond 
the 
physiological effect 
of 
that 
treatment 
is sufficient 
evidence 
for a 
hypomanic episode 
diagnosis. 
However, 
caution 
is indicated 
so 
that 
one 
or two 
symptoms (particularly increased 
irritability, 
edginess, 
or agitation 
following 
antidepressant 
use) are 
not 
taken 
as sufficient 
for diagnosis of 
a 
hypomanic 
episode, 
nor necessarily indicative 
of 
a 
bipolar diathesis. 


Major Depressive 
Episode 


A. 
Five 
(or more) of 
the 
following 
symptoms have 
been 
present 
during 
the 
same 
2week 
period 
and 
represent 
a 
change 
from previous functioning; 
at 
least 
one 
of 
the 
symptoms is either (1) depressed 
mood 
or (2) loss of 
interest 
or pleasure. 
Note: 
Do 
not 
include 
symptoms that 
are 
clearly attributable 
to 
a 
medical 
condition. 


1. 
Depressed 
mood 
most 
of 
the 
day, 
nearly every day, 
as indicated 
by either 
subjective 
report 
(e.g., 
feels sad, 
empty, 
or hopeless) or observation 
made 
by 
others (e.g., 
appears tearful). 
(Note: 
In 
children 
and 
adolescents, 
can 
be 
irritable 
mood.) 
2. 
Markedly diminished 
interest 
or pleasure 
in 
all, 
or almost 
all, 
activities most 
of 
the 
day, 
nearly every day (as indicated 
by either subjective 
account 
or 
observation). 
3. 
Significant 
weight 
loss when 
not 
dieting 
or weight 
gain 
(e.g., 
a 
change 
of 
more 
than 
5% of 
body weight 
in 
a 
month), 
or decrease 
or increase 
in 
appetite 
nearly every day. 
(Note: 
In 
children, 
consider failure 
to 
make 
expected 
weight 

gain.) 


4. 
Insomnia 
or hypersomnia 
nearly every day. 
5. 
Psychomotor agitation 
or retardation 
nearly every day (observable 
by others, 
not 
merely subjective 
feelings of 
restlessness or being 
slowed 
down). 
6. 
Fatigue 
or loss of 
energy nearly every day. 
7. 
Feelings of 
worthlessness or excessive 
or inappropriate 
guilt 
(which 
may be 
delusional) nearly every day (not 
merely self-reproach 
or guilt 
about 
being 
sick). 
8. 
Diminished 
ability to 
think or concentrate, 
or indecisiveness, 
nearly every day 
(either by subjective 
account 
or as observed 
by others). 
9. 
Recurrent 
thoughts of 
death 
(not 
just 
fear of 
dying), 
recurrent 
suicidal ideation 
without 
a 
specific plan, 
or a 
suicide 
attempt 
or a 
specific plan 
for committing 
suicide. 
B. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
C. 
The 
episode 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
or 
another medical condition. 
Note: 
Criteria 
A C constitute 
a 
major depressive 
episode. 


152 


Note: 
Responses to 
a 
significant 
loss (e.g., 
bereavement, 
financial ruin, 
losses from 
a 
natural disaster, 
a 
serious medical illness or disability) may include 
the 
feelings of 
intense 
sadness, 
rumination 
about 
the 
loss, 
insomnia, 
poor appetite, 
and 
weight 
loss 
noted 
in 
Criterion 
A, 
which 
may resemble 
a 
depressive 
episode. 
Although 
such 
symptoms may be 
understandable 
or considered 
appropriate 
to 
the 
loss, 
the 
presence 
of 
a 
major depressive 
episode 
in 
addition 
to 
the 
normal response 
to 
a 
significant 
loss should 
be 
carefully considered. 
This decision 
inevitably requires the 
exercise 
of 
clinical judgment 
based 
on 
the 
individual s history and 
the 
cultural norms 
for the 
expression 
of 
distress in 
the 
context 
of 
loss.1 


Bipolar II 
Disorder 


A. 
Criteria 
have 
been 
met 
for at 
least 
one 
hypomanic episode 
(Criteria 
A F 
under 
 Hypomanic Episode  above) and 
at 
least 
one 
major depressive 
episode 
(Criteria 
A C under  Major Depressive 
Episode  above). 
B. 
There 
has never been 
a 
manic episode. 
C. 
At 
least 
one 
hypomanic episode 
and 
at 
least 
one 
major depressive 
episode 
are 
not 
better explained 
by schizoaffective 
disorder and 
are 
not 
superimposed 
on 
schizophrenia, 
schizophreniform disorder, 
delusional disorder, 
or other specified 
or unspecified 
schizophrenia 
spectrum and 
other psychotic disorder. 
D. 
The 
symptoms of 
depression 
or the 
unpredictability caused 
by frequent 
alternation 
between 
periods of 
depression 
and 
hypomania 
causes clinically 
significant 
distress or impairment 
in 
social, 
occupational, 
or other important 

areas of 
functioning. 


Coding 
and 
Recording 
Procedures 


Bipolar II 
disorder has one 
diagnostic code: 
F31.81. 
Its status with 
respect 
to 
current 
severity, 
presence 
of 
psychotic features, 
course, 
and 
other specifiers cannot 
be 
coded 
but 
should 
be 
indicated 
in 
writing 
(e.g., 
F31.81 
bipolar II 
disorder, 
current 
episode 
depressed, 
moderate 
severity, 
with 
mixed 
features; 
F31.81 
bipolar II 
disorder, 
most 
recent 
episode 
depressed, 
in 
partial remission). 


Specify 
current 
or most 
recent 
episode: 


Hypomanic 
Depressed 
If 
current 
episode 
is hypomanic 
(or most 
recent 
episode 
if 
bipolar II 
disorder is in 
partial or full remission): 


153 


In 
recording 
the 
diagnosis, 
terms should 
be 
listed 
in 
the 
following 
order: 
bipolar II 
disorder, 
current 
or most 
recent 
episode 
hypomanic, 
in 
partial remission/in 
full 
remission 
(p. 
175) (if 
full criteria 
for a 
hypomanic episode 
are 
not 
currently met), 
plus any of 
the 
following 
hypomanic episode 
specifiers that 
are 
applicable. 
Note: 
The 
specifiers  with 
rapid 
cycling  and 
 with 
seasonal pattern  describe 
the 
pattern 
of 
mood 
episodes. 


Specify 
if: 
With 
anxious 
distress 
(p. 
169 170) 
With 
mixed 
features 
(pp. 
170 171) 
With 
rapid 
cycling 
(p. 
171) 
With 
peripartum onset 
(pp. 
173 174) 
With 
seasonal 
pattern 
(pp. 
174 175) 


If 
current 
episode 
is depressed 
(or most 
recent 
episode 
if 
bipolar II 
disorder is in 


partial or full remission): 
In 
recording 
the 
diagnosis, 
terms should 
be 
listed 
in 
the 
following 
order: 
bipolar II 
disorder, 
current 
or most 
recent 
episode 
depressed, 
mild/moderate/severe 
(if 
full 
criteria 
for a 
major depressive 
episode 
are 
currently met), 
in 
partial remission/in 
full remission 
(if 
full criteria 
for a 
major depressive 
episode 
are 
not 
currently met) 


(p. 
175), 
plus any of 
the 
following 
major depressive 
episode 
specifiers that 
are 
applicable. 
Note: 
The 
specifiers  with 
rapid 
cycling  and 
 with 
seasonal pattern  
describe 
the 
pattern 
of 
mood 
episodes. 
Specify 
if: 
With 
anxious 
distress 
(pp. 
169 170) 
With 
mixed 
features 
(pp. 
170 171) 
With 
rapid 
cycling 
(p. 
171) 
With 
melancholic 
features 
(pp. 
171 172) 



With 
atypical 
features 
(pp. 
172 173) 
With 
mood-congruent psychotic 
features 
(p. 
173) 
With 
mood-incongruent psychotic 
features 
(p. 
173) 
With 
catatonia 
(p. 
173). 
Coding 
note: 
Use 
additional code 
F06.1. 
With 
peripartum onset 
(pp. 
172 174) 
With 
seasonal 
pattern 
(pp. 
174 175) 


Specify 
course 
if 
full criteria 
for a 
mood 
episode 
are 
not 
currently met: 
In 
partial 
remission 
(p. 
175) 
In 
full 
remission 
(p. 
175) 


Specify 
severity if 
full criteria 
for a 
major depressive 
episode 
are 
currently met: 
Mild 
(p. 
175) 
Moderate 
(p. 
175) 
Severe 
(p. 
175) 


Diagnostic Features 


Bipolar II disorder is characterized by a clinical 
course of recurring mood episodes consisting of 
one or more major depressive episodes (Criteria A C 
under  Major Depressive Episode ) and at 
least 
one hypomanic episode (Criteria A F 
under  Hypomanic Episode ). A diagnosis of a major 
depressive episode requires that 
there be a period of depressed mood, or as an alternative, 
marked diminished interest 
or pleasure, for most 
of the day nearly every day, lasting for a 
minimum 
of 2 weeks. The depressed mood or loss of interest 
must 
be accompanied by additional 
symptoms occurring nearly every day (e.g., sleep disturbance, psychomotor agitation or 
retardation) for a total 
of at 
least 
five symptoms. The diagnosis of a hypomanic episode requires 
that there be a distinct period of 


154 


abnormally and persistently elevated, expansive, or irritable mood and abnormally and 
persistently increased activity or energy for most 
of the day, nearly every day, for at 
least 
4 
consecutive days accompanied by three (or four if mood is only irritable) additional 
symptoms 
(e.g., inflated self-esteem, decreased need for sleep, distractibility) that 
persist 
and represent 
a 
noticeable change from 
usual 
behavior and functioning. By definition, psychotic symptoms do 
not 
occur in hypomanic episodes, and they appear to be less frequent 
in the major depressive 
episodes in bipolar II disorder than in those of bipolar I disorder. The presence of a manic 
episode during the course of illness precludes the diagnosis of bipolar II disorder (Criterion B 
under  Bipolar II Disorder ). Moreover, for depressive and hypomanic episodes to count 
toward 
the diagnosis of bipolar II disorder, at 
least 
one of the depressive episodes and at 
least 
one of the 
hypomanic episodes must 
not 
be attributable to the physiological 
effects of a substance (i.e., 
medication, drug of abuse, or toxin exposure) or another medical 
condition. Note that 
hypomanic 
episodes that 
emerge during antidepressant 
treatment 
and persist 
for at 
least 
4 days at 
a fully 
syndromal 
level 
beyond the physiological 
effects of the treatment 
are not 
considered to be 



substance-induced and do count 
toward the diagnosis of bipolar II disorder. In addition, at 
least 
one hypomanic episode and at 
least 
one major depressive episode are not 
explained by a 
diagnosis of schizoaffective disorder and are not 
superimposed on schizophrenia, 
schizophreniform 
disorder, delusional 
disorder, or other specified or unspecified schizophrenia 
spectrum 
or other psychotic disorder (Criterion C 
under  Bipolar II Disorder ). The depressive 
episodes or the pattern of unpredictable mood changes must 
cause clinically significant 
distress 
or impairment 
in social, occupational, or other important 
areas of functioning (Criterion D under 
 Bipolar II Disorder ). The recurrent 
major depressive episodes are often more frequent 
and 
lengthier than those occurring in bipolar I disorder. 


Individuals with bipolar II disorder typically present 
to a clinician during a major depressive 
episode. They are unlikely to complain initially of hypomania, because either they do not 
recognize the symptoms of hypomania or they consider hypomania desirable. Hypomanic 
episodes by definition do not 
cause significant 
impairment. Instead, the impairment 
results from 
the major depressive episodes or from 
a persistent 
pattern of unpredictable mood changes and 
fluctuating, unreliable interpersonal 
or occupational 
functioning. Individuals with bipolar II 
disorder may not 
view the hypomanic episodes as pathological 
or disadvantageous, although 
others may be troubled by the individual s erratic behavior. Clinical 
information from 
other 
informants, such as close friends or relatives, is often useful 
in establishing the diagnosis of 
bipolar II disorder. 


A hypomanic episode should not 
be confused with the several 
days of euthymia and restored 
energy or activity that 
may follow remission of a major depressive episode. Despite the 
substantial 
differences in duration and severity between a manic and hypomanic episode, bipolar 
II disorder is not 
a  milder form  of bipolar I disorder. Compared to individuals with bipolar I 
disorder, individuals with bipolar II disorder have greater chronicity of illness and spend, on 
average, more time in the depressive phase of their illness, which can be severe and/or disabling. 


Although the diagnostic requirements for major depressive episodes are identical 
whether 
they occur in the context 
of bipolar II disorder or major depressive disorder, certain clinical 
features of the episodes may hint 
at 
possible differential 
diagnosis. For instance, the coexistence 
of both insomnia and hypersomnia is not uncommon in major depressive episodes in both bipolar 
II disorder and major depressive disorder; 
however, both insomnia and hypersomnia are 
overrepresented among women with bipolar II disorder. Similarly, atypical 
depressive symptoms 
(hypersomnia, hyperphagia) are common in both disorders, but 
more so in those with bipolar II 
disorder. 


Depressive symptoms co-occurring with a hypomanic episode or hypomanic symptoms co-
occurring with a depressive episode are common in individuals with bipolar II disorder and are 
overrepresented in females, particularly hypomania with mixed features. 


155 


Individuals experiencing hypomania with mixed features may not 
label 
their symptoms as 
hypomania, but instead experience them as depression with increased energy or irritability. 


Associated Features 


A common feature of bipolar II disorder is impulsivity, which can contribute to suicide attempts 



and substance use disorders. 


There may be heightened levels of creativity during hypomanic episodes in some individuals 
with a bipolar II disorder. However, that 
relationship may be nonlinear; 
that 
is, greater lifetime 
creative accomplishments have been associated with milder forms of bipolar disorder, and higher 
creativity has been found in unaffected family members. The individual s attachment 
to the 
prospect 
of heightened creativity during hypomanic episodes may contribute to ambivalence 
about seeking treatment or undermine adherence to treatment. 


Prevalence 


The 12-month prevalence of bipolar II disorder in the United States is 0.8%. The 12-month 
prevalence internationally is 0.3%. The prevalence rate of pediatric bipolar II disorder is difficult 
to establish. DSM-IV bipolar I, bipolar II, and bipolar disorder not 
otherwise specified yield a 
combined prevalence rate of 1.8% in U.S. and non-U.S. community samples, with higher rates 
(2.7% inclusive) in youth age 12 years or older. 


Development and Course 


Although bipolar II disorder can begin in late adolescence and 
throughout 
adulthood, average 
age at 
onset 
is the mid-20s, which is slightly later than for bipolar I disorder but 
earlier than for 
major depressive disorder. Age at 
onset 
does not 
reliably distinguish between bipolar I and II 
disorder. The illness most 
often begins with a depressive episode and is not 
recognized as bipolar 
II disorder until 
a hypomanic episode occurs; 
this happens in about 
12% of individuals with the 
initial 
diagnosis of major depressive disorder. Anxiety, substance use, or eating disorders may 
also precede the diagnosis, complicating its detection. Many individuals experience several 
episodes of major depression prior to the first 
recognized hypomanic episode, with typically a 
more than 10-year lag between illness onset and the diagnosis of a bipolar disorder. 


Bipolar II disorder is a highly recurrent 
disorder, with over 50% of individuals experiencing 
a new episode within a year after their first 
episode. Individuals with bipolar II disorder also 
have more seasonal variation in mood compared to those with bipolar I disorder. 


The number of lifetime episodes (both hypomanic and major depressive episodes) tends to be 
higher for bipolar II disorder than for major depressive disorder or bipolar I disorder. However, 
individuals with bipolar I disorder are actually more likely to experience hypomanic symptoms 
than are individuals with bipolar II disorder. The interval 
between mood episodes in the course 
of bipolar II disorder tends to decrease as the individual 
ages. While the hypomanic episode is 
the feature that 
defines bipolar II disorder, depressive episodes are more enduring and disabling 
over time. Despite the predominance of depression, once a hypomanic episode has occurred, the 
diagnosis becomes bipolar II disorder and never reverts to major depressive disorder. 


Approximately 5% 15% of individuals with bipolar II disorder have multiple (four or more) 
mood episodes (hypomanic or major depressive) within the previous 12 months. If this pattern is 
present, it 
is noted by the specifier  with rapid cycling.  Rapid cycling is more common in 
women and may reflect an overall worsening of the bipolar disorder. 


Switching from 
a depressive episode to a manic or hypomanic episode (with or without 
mixed features) may occur, both spontaneously and during treatment for depression. 


156 



About 
5% 15% of individuals with bipolar II disorder will 
ultimately develop a manic 
episode, which changes the diagnosis to bipolar I disorder, regardless of subsequent course. 


Making the diagnosis in children is often a challenge, especially in those with irritability and 
hyperarousal 
that 
is nonepisodic 
(i.e., lacks the well-demarcated periods of altered mood). 
Nonepisodic irritability in youth is associated with an elevated risk for anxiety disorders and 
major depressive disorder, but 
not 
bipolar disorder, in adulthood. Persistently irritable youth 
have lower familial 
rates of bipolar disorder than do youth who have bipolar disorder. For a 
hypomanic episode to be diagnosed, the child s symptoms must 
exceed what 
is expected in a 
given environment 
and culture for the child s developmental 
stage. Similar to adults, youth with 
bipolar II disorder spend less time hypomanic compared to those with bipolar I disorder, and the 
initial 
presenting episode is typically depression. Compared with adult 
onset 
of bipolar II 
disorder, childhood or adolescent 
onset 
of the disorder may be associated with a more severe 
lifetime course. 


The 3-year incidence rate of first-onset 
bipolar II disorder in adults older than 60 years is 
0.34%. However, distinguishing individuals older than 60 years with bipolar II disorder by late 
versus early age at 
onset 
does not 
appear to have any clinical 
utility. The presence of co-
occurring hypomanic symptoms during a depressive episode is more common during bipolar II 
depressive episodes relative to depressive episodes occurring in the context 
of major depression 
and may help distinguish older individuals with bipolar II disorder from 
those with major 
depressive disorder. In any later life presentation of bipolar disorder, it 
is important 
to consider 
medical factors, including possible medical and neurological causes of new symptoms. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
The risk of bipolar II disorder tends to be highest 
among relatives of 
individuals with bipolar II disorder, as opposed to individuals with bipolar I disorder or major 
depressive disorder. About 
a third of individuals with bipolar II disorder reported a family 
history of bipolar disorder. There may be genetic factors influencing the age at 
onset 
for bipolar 
disorders. Th ere is also evidence that 
bipolar II disorder may have a genetic architecture that 
is 
at least partially distinct from bipolar I disorder and from schizophrenia. 


Course 
modifiers. 
A rapid-cycling pattern is associated with a poorer prognosis. Return to 
previous level 
of social 
function for individuals with bipolar II disorder is more likely for 
individuals of younger age and with less severe depression, suggesting adverse effects of 
prolonged illness on recovery. More education, fewer years of illness, and being married are 
independently associated with functional 
recovery in individuals with bipolar disorder, even after 
diagnostic type (I vs. II), current 
depressive symptoms, and presence of psychiatric comorbidity 
are taken into account. 


Sex- and Gender-Related Diagnostic Issues 


Whereas the gender ratio for bipolar I disorder is equal, findings on gender differences in bipolar 
II disorder are mixed, differing by type of sample (i.e., registry, community, or clinical) and 
country of origin. There is little to no evidence of bipolar gender differences in the general 
population, whereas some, but 
not 
all, clinical 
samples suggest 
that 
bipolar II disorder is more 
common in women than in men, which may reflect 
gender differences in treatment 
seeking or 
other factors. 



Patterns of illness and comorbidity, however, seem 
to differ by sex, with females being more 
likely than males to report 
hypomania with mixed depressive features and a rapid-cycling course. 
Childbirth may also be a specific trigger for a hypomanic episode, which can occur in 10% 20% 
of females in nonclinical 
populations and most 
typically in the early postpartum 
period. 
Distinguishing hypomania from the elated mood and reduced sleep 


157 


that 
normally accompany the birth of a child may be challenging. Postpartum 
hypomania 
may foreshadow the onset 
of a depression that 
occurs in about 
half of females who experience 
postpartum 
 highs.  The perimenopause transition can also be a time of mood instability in 
bipolar II disorder. No major sex differences have been found in several 
clinical 
variables, 
including rates of depressive episodes, age at 
and polarity of onset, symptoms, and severity of 
the illness. 


Association With Suicidal 
Thoughts or Behavior 


Approximately one-third of individuals with bipolar II disorder report 
a lifetime history of 
suicide attempt. The risk and incidence of attempted suicide in bipolar II and bipolar I disorder 
appear to be similar. Overall 
there appears to be about 
equal 
rates of suicide attempts and suicide 
deaths across individuals with bipolar II and bipolar I disorder, although overall the rates for both 
attempts and deaths are significantly higher than in the general 
population. Time spent 
in a 
depressive episode is associated more significantly with the diagnosis of bipolar I or bipolar II in 
terms of suicide attempt 
risk. However, the lethality of attempts, as defined by a lower ratio of 
attempts to suicide deaths, may be higher in individuals with bipolar II disorder compared to 
individuals with bipolar I disorder. There may be an association between genetic markers and 
increased risk for suicidal 
behavior in individuals with bipolar disorder, including a 6.5-fold 
higher risk of suicide among first-degree relatives of bipolar II probands compared with first-
degree relatives of bipolar I probands. 


Functional 
Consequences of Bipolar II 
Disorder 


Although many individuals with bipolar II disorder return to a fully functional 
level 
between 
mood episodes, at 
least 
15% continue to have some interepisode dysfunction, and 20% transition 
directly into another mood episode without 
interepisode recovery. Functional 
recovery lags 
substantially behind recovery from 
symptoms of bipolar II disorder, especially in regard to 
occupational 
recovery, resulting in lower socioeconomic status despite equivalent 
levels of 
education with the general 
population. Individuals with bipolar II disorder perform 
more poorly 
than healthy individuals on cognitive tests. Cognitive impairments associated with bipolar II 
disorder may contribute to vocational 
difficulties. Prolonged unemployment 
in individuals with 
bipolar disorder is associated with more episodes of depression, older age, increased rates of 
current panic disorder, and lifetime history of alcohol use disorder. 


Differential 
Diagnosis 


Major depressive 
disorder. 
Major depressive disorder is characterized by the absence of both 
manic episodes and hypomanic episodes. Given that 
the presence of some manic or hypomanic 



symptoms (e.g., fewer symptoms or shorter duration than required for hypomania) may still 
be 
compatible with a diagnosis of major depressive disorder, it 
is important 
to ascertain whether the 
symptoms meet 
criteria for a hypomanic episode to determine whether it 
is more appropriate to 
make the diagnosis of bipolar II disorder. Depressive episodes dominate the overall 
course of 
illness for most 
individuals with bipolar II disorder, contributing to the decade-long lag between 
illness onset 
and the diagnosis of bipolar II disorder. Because the diagnostic criteria for major 
depressive episode are identical 
in major depressive disorder and bipolar II disorder, the 
diagnosis of bipolar II disorder can be made only by eliciting information about 
at 
least 
one prior 
hypomanic episode in order to distinguish the bipolar II disorder from major depressive disorder. 


Cyclothymic 
disorder. 
In cyclothymic disorder, there are numerous periods of hypomanic 
symptoms that 
do not 
meet 
symptom 
or duration criteria for a hypomanic episode and numerous 
periods of depressive symptoms that 
do not 
meet 
symptom 
or duration criteria for a major 
depressive episode. Bipolar II disorder is distinguished from 
cyclothymic disorder by the 
presence of one or more hypomanic episodes and one or more major depressive episodes. 


158 


Schizophrenia. 
Schizophrenia is characterized by active-phase psychotic symptoms that 
may be 
accompanied by major depressive episodes. The diagnosis of schizophrenia is made if no major 
depressive episodes have occurred concurrently with the active-phase symptoms. If they have 
occurred concurrently, the diagnosis of schizophrenia is made if the major depressive episodes 
have been present 
for only a minority of the time. The diagnosis is bipolar II disorder, with 
psychotic features, if the psychotic symptoms have occurred exclusively during major depressive 
episodes. 


Schizoaffective 
disorder. 
Schizoaffective disorder is characterized by periods in which depressive 
symptoms are concurrent 
with the active-phase symptoms of schizophrenia and periods in which 
delusions or hallucinations occur for at 
least 
2 weeks in the absence of a major depressive 
episode. The diagnosis is bipolar II disorder, with psychotic features, if the psychotic symptoms 
have occurred exclusively during major depressive episodes. 
Bipolar and 
related 
disorder due 
to 
another medical 
condition. 
The diagnosis of bipolar and related 


disorder due to another medical 
condition should be made instead of bipolar II disorder if the 
hypomanic episodes are judged, based on history, laboratory findings, or physical 
examination, 
to be the direct 
physiological 
consequence of another medical 
condition (e.g., Cushing s disease, 
multiple sclerosis). 
Substance/medication-induced 
bipolar and 
related 
disorder. 
A substance/medication-induced bipolar 


and related disorder is distinguished from 
bipolar II disorder by the fact 
that 
a substance (e.g., 
stimulants, phencyclidine) or medication (e.g., steroids) is judged to be etiologically related to 
the hypomanic and major depressive episodes. Because individuals with a hypomanic episode 
have a tendency to overuse substances during an episode, it 
is important 
to determine whether 
the substance use is a consequence of a primary hypomanic episode or whether the hypomaniclike 
episode has been caused by the substance use. In some cases, a definitive diagnosis may 
involve establishing that 
the hypomanic symptoms or depressive symptoms remain once the 
individual 
is no longer using the substance. Note that 
hypomanic episodes emerging in the 
context 
of treatment 
with an antidepressant 
medication but 
persisting at 
a fully syndromal 
level 



beyond the physiological 
effect 
of the medication warrant 
a diagnosis of bipolar II disorder 


rather than substance/medication-induced bipolar and related disorder. 
Attention-deficit/hyperactivity 
disorder. 
Attention-deficit/hyperactivity disorder (ADHD) may be 
misdiagnosed as bipolar II disorder, especially in adolescents and children. Many symptoms of 
ADHD, such as excessive talking, distractibility, and less need for sleep, overlap with the 
symptoms of hypomania. The double counting of symptoms toward both ADHD and bipolar II 
disorder can be avoided if the clinician clarifies whether the symptoms represent 
a distinct 
episode and if the noticeable increase over baseline required for the diagnosis of bipolar II 
disorder is present. 


Personality 
disorders. 
The same convention as applies for ADHD also applies when evaluating an 
individual 
for a personality disorder such as borderline personality disorder because mood 
lability and impulsivity are common in both personality disorders and bipolar II disorder. 
Symptoms must 
represent 
a distinct 
episode, and the noticeable increase over baseline required 
for the diagnosis of bipolar II disorder must 
be present. A diagnosis of a personality disorder 
should not 
be made during an untreated mood episode unless the lifetime history supports the 
presence of a personality disorder. 


Other bipolar disorders. 
Diagnosis of bipolar II disorder should be differentiated from 
bipolar I 
disorder by carefully considering whether there have been any past 
episodes of mania and from 
other specified and unspecified bipolar and related disorders by confirming the presence of fully 
syndromal hypomania and depression. 


159 


Comorbidity 


Bipolar II disorder is more often than not 
associated with one or more co-occurring mental 
disorders, with anxiety disorders being the most 
common. Approximately 60% of individuals 
with bipolar II disorder have three or more co-occurring mental 
disorders; 
75% have an anxiety 
disorder, most 
commonly social 
anxiety (38%), specific phobia (36%), and generalized anxiety 
(30%). Lifetime prevalence of comorbid anxiety disorder does not 
differ between bipolar I and 
bipolar II disorders but 
is associated with a worse course of illness. Children and adolescents 
with bipolar II disorder have a higher rate of co-occurring anxiety disorders compared to those 
with bipolar I disorder, and the anxiety disorder most often predates the bipolar disorder. 


Anxiety and substance use disorders occur in individuals with bipolar II disorder at 
a higher 
rate than in the general 
population. It 
should be noted that 
co-occurring anxiety and substance 
use disorder do not 
seem 
to follow a course of illness that 
is truly independent 
from 
that 
of 
bipolar II disorder, but 
rather have strong associations with mood states. For example, anxiety 
disorders tend to associate most 
with depressive symptoms, and substance use disorders are 
moderately associated with hypomanic symptoms. 


The prevalence of substance use disorders appears to be similar between bipolar I and bipolar 
II disorders, most 
commonly alcohol 
use (42%) and cannabis use (20%) disorders. Sociocultural 
factors influence the pattern of comorbid conditions in bipolar II disorder. For example, 
countries with cultural 
prohibitions against 
alcohol 
or other substance use may have a lower 
prevalence of substance use comorbidity. 


Individuals with bipolar II disorder appear to have lower rates of comorbid posttraumatic 



stress disorder compared to individuals with bipolar I disorder. 


Approximately 14% of individuals with bipolar II disorder have at 
least 
one lifetime eating 
disorder, with binge-eating disorder being more common than bulimia nervosa and anorexia 
nervosa. 


Premenstrual 
syndrome and premenstrual 
dysphoric disorder are common in women with 
bipolar disorder, especially in those with bipolar II disorder. Among women who have 
premenstrual 
syndrome and/or premenstrual 
dysphoric disorder, bipolar mood symptoms and 
lability may be more severe. 


Individuals with bipolar II disorder also have comorbid medical 
conditions, which have the 
potential 
to substantially complicate course and prognosis. These include cardiovascular disease, 
migraine, and autoimmune disorders. 


Cyclothymic Disorder 


Diagnostic Criteria 
F34.0 


A. 
For at 
least 
2 
years (at 
least 
1 
year in 
children 
and 
adolescents) there 
have 
been 
numerous periods with 
hypomanic symptoms that 
do 
not 
meet 
criteria 
for a 
hypomanic episode 
and 
numerous periods with 
depressive 
symptoms that 
do 
not 
meet 
criteria 
for a 
major depressive 
episode. 
B. 
During 
the 
above 
2-year period 
(1 
year in 
children 
and 
adolescents), 
Criterion 
A 
symptoms have 
been 
present 
for at 
least 
half 
the 
time 
and 
the 
individual has not 
been 
without 
the 
symptoms for more 
than 
2 
months at 
a 
time. 
C. 
Criteria 
for a 
major depressive, 
manic, 
or hypomanic episode 
have 
never been 
met. 
D. 
The 
symptoms in 
Criterion 
A 
are 
not 
better explained 
by schizoaffective 
disorder, 
schizophrenia, 
schizophreniform disorder, 
delusional disorder, 
or other specified 
or unspecified 
schizophrenia 
spectrum and 
other psychotic disorder. 
E. 
The 
symptoms are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition 
(e.g., 
hyperthyroidism). 
160 


F. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Specify 
if: 
With 
anxious 
distress 
(see 
pp. 
169 170) 


Diagnostic Features 


The essential 
feature of cyclothymic disorder is a chronic, fluctuating mood disturbance 



involving numerous periods of hypomanic symptoms and periods of depressive symptoms 
(Criterion A). The hypomanic symptoms are of insufficient 
number, severity, pervasiveness, 
and/or duration to meet full criteria for a hypomanic episode, and the depressive symptoms are of 
insufficient 
number, severity, pervasiveness, and/or duration to meet 
full 
criteria for a major 
depressive episode. During the initial 
2-year period (1 year for children or adolescents), the 
symptoms must 
be persistent 
(present 
more days than not), and any symptom-free intervals last 
no longer than 2 months (Criterion B). The diagnosis of cyclothymic disorder is made only if the 
criteria for a major depressive, manic, or hypomanic episode have never been met (Criterion C). 


If an individual 
with cyclothymic disorder subsequently (i.e., after the initial 
2 years in adults 
or 1 year in children or adolescents) experiences a major depressive, manic, or hypomanic 
episode, the diagnosis changes to major depressive disorder, bipolar I disorder, or other specified 
or unspecified bipolar and related disorder (subclassified as hypomanic episode without 
prior 
major depressive episode), respectively, and the cyclothymic disorder diagnosis is dropped. 


The cyclothymic disorder diagnosis is not 
made if the pattern of mood swings is better 
explained by schizoaffective disorder, schizophrenia, schizophreniform 
disorder, delusional 
disorder, or other specified and unspecified schizophrenia spectrum 
and other psychotic 
disorders (Criterion D), in which case the mood symptoms are considered associated features of 
the psychotic disorder. The mood disturbance must 
also not 
be attributable to the physiological 
effects of a substance (e.g., a drug of abuse, a medication) or another medical 
condition (e.g., 
hyperthyroidism) (Criterion E). Although some individuals may function particularly well 
during 
some of the periods of hypomania, over the prolonged course of the disorder, there must 
be 
clinically significant 
distress or impairment 
in social, occupational, or other important 
areas of 
functioning as a result 
of the mood disturbance (Criterion F). The prolonged pattern of repeated, 
often unpredictable mood changes may lead to impairment 
attributable to the negative effects of 
the symptoms themselves combined with negative effects that 
the pattern of unpredictability and 
inconsistency has on interpersonal 
functioning and role performance (i.e., familial, occupational 
roles). 


Prevalence 


The lifetime prevalence of cyclothymic disorder in the United States and Europe is 
approximately 0.4% 2.5%. Prevalence in mood disorders clinics may range from 
3% to 5%. In 
the general 
population, cyclothymic disorder is apparently equally common in males and 
females. In clinical 
settings, females with cyclothymic disorder may be more likely to present 
for 
treatment than males. 


Development and Course 


Cyclothymic disorder usually begins in adolescence or early adult 
life and is sometimes 
considered to reflect 
a temperamental 
predisposition to other disorders in this chapter. The vast 
majority of youth with cyclothymic disorder experience the onset 
of mood symptoms before age 


10. Cyclothymic disorder usually has an insidious onset 
and a persistent 
course. There is a 15%  
50% risk that an individual with cyclothymic disorder will 
161 



subsequently develop bipolar I disorder or bipolar II disorder; 
diagnostic conversion rates are 
higher in youth than in adults. Onset 
of persistent, fluctuating hypomanic and depressive 
symptoms late in adult 
life needs to be clearly differentiated from 
bipolar and related disorder 
due to another medical 
condition and depressive disorder due to another medical 
condition (e.g., 
multiple sclerosis) before the cyclothymic disorder diagnosis is assigned. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Major depressive disorder, bipolar I disorder, and bipolar II disorder 
are more common among first-degree biological 
relatives of individuals with cyclothymic 
disorder than in the general 
population. There may also be an increased familial 
risk of 
substance-related disorders. Cyclothymic disorder may be more common in the first-degree 
biological relatives of individuals with bipolar I disorder than in the general population. 


Differential 
Diagnosis 


Bipolar and 
related 
disorder due 
to 
another medical 
condition. 
The diagnosis of bipolar and related 
disorder due to another medical 
condition is made when the mood disturbance is judged to be 
attributable to the physiological 
effect 
of a specific, usually chronic medical 
condition (e.g., 
hyperthyroidism). This determination is based on the history, physical 
examination, and/or 
laboratory findings. If it 
is judged that 
the hypomanic and depressive symptoms are not 
the 
physiological 
consequence of the medical 
condition, then the primary mental 
disorder (i.e., 
cyclothymic disorder) and the medical 
condition are coded. For example, this would be the case 
if the mood symptoms are considered to be the psychological 
(not 
the physiological) 
consequence of having a chronic medical 
condition, or if there is no etiological 
relationship 
between the hypomanic and depressive symptoms and the medical condition. 


Substance/medication-induced 
bipolar and 
related 
disorder and 
substance/medication-induced 
depressive 
disorder. 


Substance/medication-induced bipolar and related disorder and substance/medication-induced 
depressive disorder are distinguished from 
cyclothymic disorder by the judgment 
that 
a 
substance/medication (especially stimulants) is etiologically related to the mood disturbance. The 
frequent 
mood swings in these disorders that 
are suggestive of cyclothymic disorder usually 
resolve following cessation of substance/medication use. 
Bipolar I 
disorder, 
with 
rapid 
cycling, 
and 
bipolar II 
disorder, 
with 
rapid 
cycling. 
Both disorders may 


resemble cyclothymic disorder by virtue of the frequent 
marked shifts in mood. By definition, in 
cyclothymic disorder the criteria for a major depressive, manic, or hypomanic episode have 
never been met, whereas the bipolar I disorder and bipolar II disorder specifier  with rapid 
cycling  requires that full mood episodes be present. 


Borderline 
personality 
disorder. 
Borderline personality disorder is associated with recurrent, brief 
marked shifts in mood that 
may suggest 
cyclothymic disorder. Engagement 
in potentially self-
damaging behaviors can be seen in both conditions but 
would need to occur in the context 
of 
other hypomanic symptoms to be related to cyclothymia. Mood instability in borderline 
personality disorder occurs in the domains of anxiety, irritability, and sadness, whereas elation, 
euphoria, and/or increased energy are not 
characteristic features of borderline personality 
disorder. If the criteria are met 
for both disorders, both borderline personality disorder and 
cyclothymic disorder may be diagnosed. 



Comorbidity 


Substance-related disorders and sleep disorders (i.e., difficulties in initiating and maintaining 
sleep) may be present in individuals with cyclothymic disorder. Rates of comorbid 


162 


psychiatric disorders in children with cyclothymic disorder treated in outpatient 
psychiatric 
settings are greater than those in children with disruptive behavior/attention-deficit/hyperactivity 
disorder and similar to those in children with bipolar I or II disorder. 


Substance/Medication-Induced 
Bipolar and 
Related 
Disorder 


Diagnostic Criteria 


A. 
A 
prominent 
and 
persistent 
disturbance 
in 
mood 
that 
predominates in 
the 
clinical 
picture 
and 
is characterized 
by abnormally elevated, 
expansive, 
or irritable 
mood 
and 
abnormally increased 
activity or energy. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
of 
both 
(1) and 
(2): 
1. 
The 
symptoms in 
Criterion 
A 
developed 
during 
or soon 
after substance 
intoxication 
or withdrawal or after exposure 
to 
or withdrawal from a 
medication. 
2. 
The 
involved 
substance/medication 
is capable 
of 
producing 
the 
symptoms in 
Criterion 
A. 
C. 
The 
disturbance 
is not 
better explained 
by a 
bipolar or related 
disorder that 
is not 
substance/medication-induced. 
Such 
evidence 
of 
an 
independent 
bipolar or 
related 
disorder could 
include 
the 
following: 
The 
symptoms precede 
the 
onset 
of 
the 
substance/medication 
use; 
the 
symptoms persist 
for a 
substantial period 
of 
time 
(e.g., 
about 
1 
month) after 
the 
cessation 
of 
acute 
withdrawal or severe 
intoxication; 
or there 
is other 
evidence 
suggesting 
the 
existence 
of 
an 
independent 
non-
substance/medication-induced 
bipolar and 
related 
disorder (e.g., 
a 
history of 
recurrent 
non-substance/medication-related 
episodes). 


D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Note: 
This diagnosis should 
be 
made 
instead 
of 
a 
diagnosis of 
substance 
intoxication 
or substance 
withdrawal only when 
the 
symptoms in 
Criterion 
A 
predominate 
in 
the 
clinical picture 
and 
when 
they are 
sufficiently severe 
to 
warrant 



clinical attention. 
Coding 
note: 
The 
ICD-10-CM codes for the 
[specific substance/medication]-induced 
bipolar and 
related 
disorders are 
indicated 
in 
the 
table 
below. 
Note 
that 
the 
ICD-10CM 
code 
depends on 
whether or not 
there 
is a 
comorbid 
substance 
use 
disorder 
present 
for the 
same 
class of 
substance. 
In 
any case, 
an 
additional separate 
diagnosis of 
a 
substance 
use 
disorder is not 
given. 
If 
a 
mild 
substance 
use 
disorder 
is comorbid 
with 
the 
substance-induced 
bipolar and 
related 
disorder, 
the 
4th 
position 
character is  1,  and 
the 
clinician 
should 
record 
 mild 
[substance] 
use 
disorder  
before 
the 
substance-induced 
bipolar and 
related 
disorder (e.g., 
 mild 
cocaine 
use 
disorder with 
cocaine-induced 
bipolar and 
related 
disorder ). 
If 
a 
moderate 
or severe 
substance 
use 
disorder is comorbid 
with 
the 
substance-induced 
bipolar and 
related 
disorder, 
the 
4th 
position 
character is  2,  and 
the 
clinician should 
record 
 moderate 
[substance] 
use 
disorder  or  severe 
[substance] 
use 
disorder,  depending 
on 
the 
severity of 
the 
comorbid 
substance 
use 
disorder. 
If 
there 
is no 
comorbid 
substance 
use 
disorder (e.g., 
after a 
one-time 
heavy use 
of 
the 
substance), 
then 
the 
4th 
position 
character is  9,  and 
the 
clinician 
should 
record 
only the 
substance-induced 
bipolar and 
related 
disorder. 


163 


ICD-10-CM 


With 
mild 
use 
With 
moderate 
or 
Without 
use 
disorder 
severe 
use 
disorder 
disorder 
Alcohol 
F10.14 
F10.24 
F10.94 
Phencyclidine 
F16.14 
F16.24 
F16.94 
Other 
hallucinogen 
F16.14 
F16.24 
F16.94 
Sedative, 
hypnotic, 
or 
anxiolytic 
F13.14 
F13.24 
F13.94 
Amphetamine-type 
substance 
(or 
other 
stimulant) 
F15.14 
F15.24 
F15.94 
Cocaine 
F14.14 
F14.24 
F14.94 
Other 
(or 
unknown) 
substance 
F19.14 
F19.24 
F19.94 


Specify 
(see 
Table 
1 
in 
the 
chapter  Substance-Related 
and 
Addictive 
Disorders,  
which 
indicates whether  with 
onset 
during 
intoxication  and/or  with 
onset 
during 
withdrawal  applies to 
a 
given 
substance 
class; 
or specify 
 with 
onset 
after 
medication 
use ): 


With 
onset during 
intoxication: 
If 
criteria 
are 
met 
for intoxication 
with 
the 


substance 
and 
the 
symptoms develop 
during 
intoxication. 
With 
onset during 
withdrawal: 
If 
criteria 
are 
met 
for withdrawal from the 
substance 
and 
the 
symptoms develop 
during, 
or shortly after, 
withdrawal. 


With 
onset after medication 
use: 
If 
symptoms developed 
at 
initiation 
of 
medication, 
with 
a 
change 
in 
use 
of 
medication, 
or during 
withdrawal of 
medication. 



Recording Procedures 


The name of the substance/medication-induced bipolar and related disorder begins with the 
specific substance (e.g., cocaine, dexamethasone) that 
is presumed to be causing the bipolar 
mood symptoms. The diagnostic code is selected from 
the table included in the criteria set, 
which is based on the drug class and presence or absence of a comorbid substance use disorder. 
For substances that 
do not 
fit 
into any of the classes (e.g., dexamethasone), the code for  other 
(or unknown) substance  should be used; 
and in cases in which a substance is judged to be an 
etiological 
factor but 
the specific class of substance is unknown, the same code should also be 
used. 


When recording the name of the disorder, the comorbid substance use disorder (if any) is 
listed first, followed by the word  with,  followed by the name of the substance-induced bipolar 
and related disorder, followed by the specification of onset 
(i.e., onset 
during intoxication, onset 
during withdrawal). For example, in the case of irritable symptoms occurring during intoxication 
in a man with a severe cocaine use disorder, the diagnosis is F14.24 severe cocaine use disorder 
with cocaine-induced bipolar and related disorder, with onset 
during intoxication. A separate 
diagnosis of the comorbid severe cocaine use disorder is not 
given. If the substance-induced 
bipolar and related disorder occurs without 
a comorbid substance use disorder (e.g., after a onetime 
heavy use of the substance), no accompanying substance use disorder is noted (e.g., F15.94 
amphetamine-induced bipolar and related disorder, with onset 
during intoxication). When more 
than one substance is judged to play a significant 
role in the development 
of bipolar mood 
symptoms, each should be listed separately (e.g., F15.24 severe methylphenidate use disorder 
with methylphenidate-induced bipolar and related disorder, with onset 
during intoxication; 
F19.94 dexamethasone-induced bipolar and related disorder, with onset during intoxication). 


164 


Diagnostic Features 


The essential 
feature of substance/medication-induced bipolar and related disorder is a prominent 
and persistent 
disturbance in mood that 
predominates in the clinical 
picture and is characterized 
by abnormally elevated, expansive, or irritable mood and abnormally increased activity or energy 
(Criterion A); 
these symptoms are judged to be attributable to the effects of a substance (e.g., a 
drug of abuse, a medication, or a toxin exposure) (Criterion B). 


To meet 
criteria for the diagnosis, the abnormally elevated, expansive, or irritable mood and 
increased activity or energy must 
have developed during or soon after substance intoxication or 
withdrawal 
or after exposure to or withdrawal 
from 
a medication, as evidenced by clinical 
history, physical 
examination, or laboratory findings (Criterion B1), and the involved 
substance/medication must 
be capable of producing the abnormally elevated, expansive, or 
irritable mood and increased activity or energy (Criterion B2). In addition, the abnormally 
elevated, expansive, or irritable mood and increased activity or energy are not 
better explained 
by a non-substance/medication-induced bipolar and related disorder. 


Evidence of an independent 
bipolar and related disorder includes the observation that 
the 
abnormally elevated, expansive, or irritable mood and increased activity or energy preceded the 
onset of substance/medication use, the symptoms persist beyond a substantial period of time after 
the cessation of acute withdrawal 
or severe intoxication (i.e., usually longer than 1 month), or 



there is other evidence that 
suggests the existence of an independent 
non-substance/medicationinduced 
bipolar and related disorder (Criterion C), such as a history of recurrent 
non-substanceinduced 
manic episodes. Diagnosis of substance/medication-induced bipolar and related disorder 
should not 
be made when symptoms occur exclusively during the course of a delirium 
(Criterion 
D). Finally, the diagnosis requires that 
the substance/medication-induced symptoms cause 
clinically significant 
distress or impairment 
in social, occupational, or other important 
areas of 
functioning (Criterion E). The substance-induced bipolar and related disorder diagnosis should 
be made instead of a diagnosis of substance intoxication or substance withdrawal 
only when the 
symptoms in Criterion A predominate in the clinical 
picture and are sufficiently severe to 
warrant independent clinical attention. 


A key exception to the diagnosis of substance/medication-induced bipolar and related 
disorder is the case of hypomania or mania that 
occurs after antidepressant 
medication use or 
other treatments and persists beyond the physiological 
effects of the medication. The persistence 
of hypomania or mania is considered an indicator of true bipolar disorder, not 
substance/medication-induced bipolar and related disorder. Similarly, individuals with apparent 
electroconvulsive therapy induced manic or hypomanic episodes that 
persist 
beyond the 
physiological 
effects of the treatment 
are diagnosed with bipolar disorder, not 
substance/medication-induced bipolar and related disorder. Furthermore, substance/medicationinduced 
bipolar and related symptoms may suggest 
an underlying bipolar diathesis in individuals 
previously not diagnosed with bipolar disorders. 


Side effects of some antidepressants and other psychotropic drugs (e.g., edginess, agitation) 
may resemble the primary symptoms of a manic syndrome, but 
they are fundamentally distinct 
from 
bipolar symptoms and are insufficient 
for the diagnosis. That 
is, the criterion symptoms of 
mania/hypomania have specificity (simple agitation is not 
the same as excess involvement 
in 
purposeful 
activities), and a sufficient 
number of symptoms must 
be present 
(not 
just 
one or two 
symptoms) to make these diagnoses. In particular, the appearance of one or two nonspecific 
symptoms irritability, edginess, or agitation during antidepressant 
treatment in the absence of 
a full 
manic or hypomanic syndrome should not 
be taken to support 
a diagnosis of a bipolar 
disorder. 


Associated Features 


Substances/medications that 
are typically considered to be associated with substance/medicationinduced 
bipolar and related disorder include the stimulant class of drugs, as 


165 


well 
as phencyclidine and steroids; 
however, a number of potential 
substances continue to 
emerge as new compounds are synthesized (e.g., so-called bath salts). 


Prevalence 


Limited epidemiological 
data exist 
regarding the prevalence of substance/medication-induced 
mania or bipolar disorder. Prevalence of substance-induced bipolar disorder will 
depend on 
substance availability and level 
of substance use in a society; 
for example, countries with cultural 
prohibitions against 
alcohol 
or other substance use may have a lower prevalence of substance



related disorders. 


Development and Course 


In phencyclidine-induced mania, the initial 
presentation may be one of a delirium 
with affective 
features, which then becomes an atypically appearing manic or mixed manic state. This condition 
follows the ingestion or inhalation quickly, usually within hours or, at 
the most, a few days. In 
stimulant-induced manic or hypomanic states, the response is in minutes to 1 hour after one or 
several 
ingestions or injections. The episode is very brief and typically resolves over 1 2 days. 
With corticosteroids and some immunosuppressant 
medications, the mania (or mixed or 
depressed state) usually follows several 
days of ingestion, and the higher doses appear to have a 
much greater likelihood of producing bipolar symptoms. 


Diagnostic Markers 


Determination of the substance of use can be made through markers in the blood or urine to 
corroborate diagnosis. 


Differential 
Diagnosis 


Substance/medication-induced bipolar and related disorder should be differentiated from 
other 
bipolar disorders, substance intoxication, substance withdrawal, substance-induced delirium, and 
medication side effects (as noted earlier). A full 
manic episode that 
emerges during 
antidepressant 
treatment 
(e.g., medication, electroconvulsive therapy) but 
persists at 
a fully 
syndromal 
level 
beyond the physiological 
effect 
of that 
treatment 
is sufficient 
evidence for a 
bipolar I diagnosis. A full 
hypomanic episode that 
emerges during antidepressant 
treatment 
(e.g., 
medication, electroconvulsive therapy) but 
persists at 
a fully syndromal 
level 
beyond the 
physiological 
effect 
of that 
treatment 
is sufficient 
evidence for a bipolar II diagnosis only if 
preceded by a major depressive episode. 
Substance 
intoxication 
and 
substance 
withdrawal. 
Euphoria, irritability, and increased energy may 


occur in substance intoxication (e.g., stimulant 
intoxication) or substance withdrawal 
(e.g., 
cannabis withdrawal). The diagnosis of the substance-specific intoxication or substance-specific 
withdrawal 
will 
usually suffice to categorize the symptom 
presentation. A diagnosis of 
substance/medication-induced bipolar and related disorder either with onset 
during intoxication 
or with onset 
during withdrawal 
should be made instead of a diagnosis of substance intoxication 
or substance withdrawal 
when the euphoric or irritable mood or increased energy symptoms are 
predominant in the clinical picture and are sufficiently severe to warrant clinical attention. 


Comorbidity 


Comorbidities are those associated with the use of illicit 
substances (in the case of illegal 
stimulants or phencyclidine) or diversion of prescribed stimulants. Comorbidities related to 
steroid or immunosuppressant 
medications are those medical 
indications for these preparations. 
Delirium 
can occur before or along with manic symptoms in individuals ingesting phencyclidine 
or those who are prescribed steroid medications or other immunosuppressant medications. 


166 



Bipolar and 
Related 
Disorder Due to 
Another Medical 
Condition 


Diagnostic Criteria 


A. 
A 
prominent 
and 
persistent 
disturbance 
in 
mood 
that 
predominates in 
the 
clinical 
picture 
and 
is characterized 
by abnormally elevated, 
expansive, 
or irritable 
mood 
and 
abnormally increased 
activity or energy. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
that 
the 
disturbance 
is the 
direct 
pathophysiological consequence 
of 
another 
medical condition. 
C. 
The 
disturbance 
is not 
better explained 
by another mental disorder. 
D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning, 
or necessitates 
hospitalization 
to 
prevent 
harm to 
self 
or others, 
or there 
are 
psychotic features. 
Coding 
note: 
The 
ICD-10-CM code 
depends on 
the 
specifier (see 
below). 
Specify 
if: 


F06.33 
With 
manic 
features: 
Full criteria 
are 
not 
met 
for a 
manic or hypomanic 
episode. 
F06.33 
With 
manic- or hypomanic-like 
episode: 
Full criteria 
are 
met 
except 


Criterion 
D for a 
manic episode 
or except 
Criterion 
F 
for a 
hypomanic episode. 
F06.34 
With 
mixed 
features: 
Symptoms of 
depression 
are 
also 
present 
but 
do 
not 
predominate 
in 
the 
clinical picture. 
Coding 
note: 
Include 
the 
name 
of 
the 
other medical condition 
in 
the 
name 
of 
the 
mental disorder (e.g., 
F06.33 
bipolar disorder due 
to 
hyperthyroidism, 
with 
manic 
features). 
The 
other medical condition 
should 
also 
be 
coded 
and 
listed 
separately 
immediately before 
the 
bipolar and 
related 
disorder due 
to 
the 
medical condition 
(e.g., 
E05.90 
hyperthyroidism; 
F06.33 
bipolar disorder due 
to 
hyperthyroidism, 
with 
manic features). 


Diagnostic Features 


The essential 
features of bipolar and related disorder due to another medical 
condition are 
presence of a prominent 
and persistent 
period of abnormally elevated, expansive, or irritable 
mood and abnormally increased activity or energy predominating in the clinical 
picture 
(Criterion A) that 
is attributable to another medical 
condition (Criterion B). In most 
cases the 
manic or hypomanic picture may appear during the initial 
presentation of the medical 
condition 
(i.e., within 1 month); 
however, there are exceptions, especially in chronic medical 
conditions 
that 
might 
worsen or relapse and herald the appearance of the manic or hypomanic picture. 
Bipolar and related disorder due to another medical 
condition would not 
be diagnosed when the 



manic or hypomanic episodes definitely preceded the medical 
condition, because the proper 
diagnosis would be bipolar disorder (except 
in the unusual 
circumstance in which all 
preceding 
manic or hypomanic episodes or, when only one such episode has occurred, the preceding 
manic or hypomanic episode were associated with ingestion of a substance/medication). The 
diagnosis of bipolar and related disorder due to another medical 
condition should not 
be made 
during the course of a delirium 
(Criterion D). The manic or hypomanic episode in bipolar and 
related disorder due to another medical 
condition must 
cause clinically significant 
distress or 
impairment 
in social, occupational, or other important 
areas of functioning to qualify for this 
diagnosis (Criterion E). 


167 


Associated Features 


The listing of medical 
conditions that 
are said to be able to induce mania is never complete, and 
the clinician s best 
judgment 
is the essence of this diagnosis. Among the best 
known of the 
medical 
conditions that 
can cause a bipolar manic or hypomanic condition are Cushing s disease 
and multiple sclerosis, as well 
as stroke and traumatic brain injuries. Antibodies to the N-methylD-
aspartate (NMDA) receptor have been associated with manic or mixed mood and psychotic 
symptoms. In such cases, the causative medical 
condition would be anti-NMDA receptor 
encephalitis. 


Development and Course 


Bipolar and related disorder due to another medical 
condition usually has its onset 
acutely or 
subacutely within the first 
weeks or month of the onset 
of the associated medical 
condition. 
However, this is not 
always the case, as a worsening or later relapse of the associated medical 
condition may precede the onset 
of the manic or hypomanic syndrome. The clinician must 
make 
a clinical 
judgment 
in these situations about 
whether the medical 
condition is causative, based on 
temporal 
sequence as well 
as plausibility of a causal 
relationship. Finally, the condition may 
remit 
before or just 
after the medical 
condition remits, particularly when treatment 
of the 
manic/hypomanic symptoms is effective. 


Culture-Related Diagnostic Issues 


Culture-related differences, to the extent 
that 
there is any evidence, pertain to those associated 
with the medical 
condition (e.g., rates of multiple sclerosis and stroke vary around the world 
based on dietary factors, genetic factors, and other environmental factors). 


Sex- and Gender-Related Diagnostic Issues 


Gender differences pertain to those associated with the medical 
condition (e.g., systemic lupus 
erythematosus is more common in females; 
stroke is somewhat 
more common in middle-age 
males compared with females). 


Diagnostic Markers 


Diagnostic markers pertain to those associated with the medical 
condition (e.g., steroid levels in 



blood or urine to help corroborate the diagnosis of Cushing s disease, which can be associated 
with manic or depressive syndromes; 
laboratory tests confirming the diagnosis of multiple 
sclerosis). 


Functional 
Consequences of Bipolar and Related Disorder Due to 
Another Medical 
Condition 


Functional 
consequences of the bipolar symptoms may exacerbate impairments associated with 
the medical 
condition and may incur worse outcomes because of interference with medical 
treatment. 


Differential 
Diagnosis 


Delirium and 
major or mild 
neurocognitive 
disorder. 
A separate diagnosis of bipolar and related 
disorder due to another medical condition is not given if the mood disturbance occurs exclusively 
during the course of a delirium. However, a diagnosis of bipolar and related disorder due to 
another medical 
condition may be given in addition to a diagnosis of major or mild 
neurocognitive disorder if the mood disturbance is judged to be a physiological 
consequence of 
the pathological 
process causing the neurocognitive disorder and if symptoms of irritability or 
elevated mood are a prominent part of the clinical presentation. 


168 


Symptoms 
of 
catatonia 
and 
acute 
anxiety. 
It 
is important 
to differentiate symptoms of mania from 
excited catatonic symptoms and from agitation related to acute anxiety states. 
Medication-induced 
depressive 
or manic 
symptoms. 
An important 
differential 
diagnostic observation 


is that 
the other medical 
condition may be treated with medications (e.g., steroids or alpha-
interferon) that 
can induce depressive or manic symptoms. In these cases, clinical 
judgment 
using all 
of the evidence in hand is the best 
way to try to separate the most 
likely and/or the most 
important 
of two etiological 
factors (i.e., association with the medical 
condition vs. a 
substance/medication-induced syndrome). The differential 
diagnosis of the associated medical 
conditions is relevant but largely beyond the scope of the present manual. 


Comorbidity 


Conditions comorbid with bipolar and related disorder due to another medical 
condition are 
those associated with the medical 
conditions of etiological 
relevance. Delirium 
can occur before 
or along with manic symptoms in individuals with Cushing s disease. 


Other Specified 
Bipolar and 
Related 
Disorder 


F31.89 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
bipolar 
and 
related 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 



occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
bipolar and 
related 
disorders diagnostic 
class. 
The 
other specified 
bipolar and 
related 
disorder category is used 
in 
situations 
in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific bipolar and 
related 
disorder. 
This is done 
by recording 
 other specified 
bipolar and 
related 
disorder  followed 
by 
the 
specific reason 
(e.g., 
 short-duration 
cyclothymia ). 


Examples of 
presentations that 
can 
be 
specified 
using 
the 
 other specified  
designation 
include 
the 
following: 


1. 
Short-duration 
hypomanic 
episodes 
(2 3 
days) and 
major depressive 
episodes: 
A 
lifetime 
history of 
one 
or more 
major depressive 
episodes in 
individuals whose 
presentation 
has never met 
full criteria 
for a 
manic or 
hypomanic episode 
but 
who 
have 
experienced 
two 
or more 
episodes of 
short-
duration 
hypomania 
that 
meet 
the 
full symptomatic criteria 
for a 
hypomanic 
episode 
but 
that 
only last 
for 2 3 
days. 
The 
episodes of 
hypomanic symptoms do 
not 
overlap 
in 
time 
with 
the 
major depressive 
episodes, 
so 
the 
disturbance 
does 
not 
meet 
criteria 
for major depressive 
episode, 
with 
mixed 
features. 
2. 
Hypomanic 
episodes 
with 
insufficient symptoms 
and 
major depressive 
episodes: 
A 
lifetime 
history of 
one 
or more 
major depressive 
episodes in 
individuals whose 
presentation 
has never met 
full criteria 
for a 
manic or 
hypomanic episode 
but 
who 
have 
experienced 
one 
or more 
episodes of 
hypomania 
that 
do 
not 
meet 
full symptomatic criteria 
(i.e., 
at 
least 
4 
consecutive 
days of 
elevated 
mood 
and 
one 
or two 
of 
the 
other symptoms of 
a 
hypomanic 
episode, 
or irritable 
mood 
and 
two 
or three 
of 
the 
other symptoms of 
a 
hypomanic episode). 
The 
episodes of 
hypomanic symptoms do 
not 
overlap 
in 
time 
with 
the 
major depressive 
episodes, 
so 
the 
disturbance 
does not 
meet 
criteria 
for major depressive 
episode, 
with 
mixed 
features. 
3. 
Hypomanic 
episode 
without prior major depressive 
episode: 
One 
or more 
hypomanic episodes in 
an 
individual whose 
presentation 
has never met 
full 
criteria 
for a 
major depressive 
episode 
or a 
manic episode. 
169 


4. 
Short-duration 
cyclothymia 
(less 
than 
24 
months): 
Multiple 
episodes of 
hypomanic symptoms that 
do 
not 
meet 
criteria 
for a 
hypomanic episode 
and 
multiple 
episodes of 
depressive 
symptoms that 
do 
not 
meet 
criteria 
for a 
major 
depressive 
episode 
that 
persist 
over a 
period 
of 
less than 
24 
months (less than 
12 
months for children 
or adolescents) in 
an 
individual whose 
presentation 
has 
never met 
full criteria 
for a 
major depressive, 
manic, 
or hypomanic episode 
and 
does not 
meet 
criteria 
for any psychotic disorder. 
During 
the 
course 
of 
the 
disorder, 
the 
hypomanic or depressive 
symptoms are 
present 
for more 
days than 
not, 
the 
individual has not 
been 
without 
symptoms for more 
than 
2 
months at 
a 
time, 
and 
the 
symptoms cause 
clinically significant 
distress or impairment. 
5. 
Manic 
episode 
superimposed 
on 
schizophrenia, 
schizophreniform disorder, 
delusional disorder, 
or other specified 
and 
unspecified 
schizophrenia 
spectrum 

and 
other psychotic disorder. 
Note: 
Manic episodes that 
are 
part 
of 
schizoaffective 
disorder do 
not 
merit 
an 
additional diagnosis of 
other specified 
bipolar and 
related 
disorder. 


Unspecified 
Bipolar and 
Related 
Disorder 


F31.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
bipolar 
and 
related 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
bipolar and 
related 
disorders diagnostic 
class. 
The 
unspecified 
bipolar and 
related 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for 
a 
specific bipolar and 
related 
disorder, 
and 
includes presentations in 
which 
there 
is 
insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room 
settings). 


Unspecified 
Mood 
Disorder 


F39 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
mood 
dis-order that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
at 
the 
time 
of 
the 
evaluation 
meet 
the 
full criteria 
for any of 
the 
disorders in 
either the 
bipolar or the 
depressive 
disorders diagnostic classes and 
in 
which 
it 
is difficult 
to 
choose 
between 
unspecified 
bipolar and 
related 
disorder and 
unspecified 
depressive 
disorder (e.g., 
acute 
agitation). 


Specifiers for Bipolar and 
Related 
Disorders 


Specify 
if: 


With 
anxious 
distress: 
The 
presence 
of 
at 
least 
two 
of 
the 
following 
symptoms 


during 
the 
majority of 
days of 
the 
current 
manic, 
hypomanic, 
or major depressive 


episode 
in 
bipolar I 
disorder (or the 
most 
recent 
episode 
if 
bipolar I 
disorder is in 


partial or full remission); 
or of 
the 
current 
hypomanic or major depressive 


episode 
in 
bipolar II 
disorder (or the 
most 
recent 
episode 
if 
bipolar II 
disorder is 


in 
partial or full remission); 
or during 
the 
majority of 
symptomatic days in 


cyclothymic disorder: 



1. 
Feeling 
keyed 
up 
or tense. 
2. 
Feeling 
unusually restless. 
170 


3. 
Difficulty concentrating 
because 
of 
worry. 
4. 
Fear that 
something 
awful may happen. 
5. 
Feeling 
that 
the 
individual might 
lose 
control of 
himself 
or herself. 
Specify 
current 
severity: 
Mild: 
Two 
symptoms. 
Moderate: 
Three 
symptoms. 
Moderate-severe: 
Four or five 
symptoms. 
Severe: 
Four or five 
symptoms with 
motor agitation. 


Note: 
Anxious distress has been 
noted 
as a 
prominent 
feature 
of 
both 
bipolar 
and 
major depressive 
disorders in 
both 
primary care 
and 
specialty mental 
health 
settings. 
High 
levels of 
anxiety have 
been 
associated 
with 
higher 
suicide 
risk, 
longer duration 
of 
illness, 
and 
greater likelihood 
of 
treatment 
nonresponse. 
As a 
result, 
it 
is clinically useful to 
specify accurately the 
presence 
and 
severity levels of 
anxious distress for treatment 
planning 
and 
monitoring 
of 
response 
to 
treatment. 


With 
mixed 
features: 
The 
mixed 
features specifier can 
apply to 
the 
current 
manic, 
hypomanic, 
or major depressive 
episode 
in 
bipolar I 
disorder (or the 
most 
recent 
episode 
if 
bipolar I 
disorder is in 
partial or full remission) or to 
the 
current 
hypomanic or major depressive 
episode 
in 
bipolar II 
disorder (or the 
most 
recent 
episode 
if 
bipolar II 
disorder is in 
partial or full remission): 


Manic 
or hypomanic 
episode, 
with 
mixed 
features: 


A. 
Full criteria 
are 
met 
for a 
manic episode 
or hypomanic episode, 
and 
at 
least 
three 
of 
the 
following 
symptoms are 
present 
during 
the 
majority of 
days of 
the 
current 
or most 
recent 
episode 
of 
mania 
or hypomania: 
1. 
Prominent 
dysphoria 
or depressed 
mood 
as indicated 
by either 
subjective 
report 
(e.g., 
feels sad 
or empty) or observation 
made 
by 
others (e.g., 
appears tearful). 
2. 
Diminished 
interest 
or pleasure 
in 
all, 
or almost 
all, 
activities (as 
indicated 
by either subjective 
account 
or observation 
made 
by others). 
3. 
Psychomotor retardation 
nearly every day (observable 
by others; 
not 
merely subjective 
feelings of 
being 
slowed 
down). 
4. 
Fatigue 
or loss of 
energy. 
5. 
Feelings of 
worthlessness or excessive 
or inappropriate 
guilt 
(not 
merely 
self-reproach 
or guilt 
about 
being 
sick). 
6. 
Recurrent 
thoughts of 
death 
(not 
just 
fear of 
dying), 
recurrent 
suicidal 
ideation 
without 
a 
specific plan, 
or a 
suicide 
attempt 
or a 
specific plan 
for 

committing 
suicide. 


B. 
Mixed 
symptoms are 
observable 
by others and 
represent 
a 
change 
from the 
person s usual behavior. 
C. 
For individuals whose 
symptoms meet 
full episode 
criteria 
for both 
mania 
and 
depression 
simultaneously, 
the 
diagnosis should 
be 
manic episode, 
with 
mixed 
features, 
due 
to 
the 
marked 
impairment 
and 
clinical severity of 
full mania. 
D. 
The 
mixed 
symptoms are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication 
or other treatment). 
Depressive 
episode, 
with 
mixed 
features: 


A. 
Full criteria 
are 
met 
for a 
major depressive 
episode, 
and 
at 
least 
three 
of 
the 
following 
manic/hypomanic symptoms are 
present 
during 
the 
majority of 
days of 
the 
current 
or most 
recent 
episode 
of 
depression: 
1. 
Elevated, 
expansive 
mood. 
2. 
Inflated 
self-esteem or grandiosity. 
171 


3. 
More 
talkative 
than 
usual or pressure 
to 
keep 
talking. 
4. 
Flight 
of 
ideas or subjective 
experience 
that 
thoughts are 
racing. 
5. 
Increase 
in 
energy or goal-directed 
activity (either socially, 
at 
work or 
school, 
or sexually). 
6. 
Increased 
or excessive 
involvement 
in 
activities that 
have 
a 
high 
potential for painful consequences (e.g., 
engaging 
in 
unrestrained 
buying 
sprees, 
sexual indiscretions, 
or foolish 
business investments). 
7. 
Decreased 
need 
for sleep 
(feeling 
rested 
despite 
sleeping 
less than 
usual; 
to 
be 
contrasted 
with 
insomnia). 
B. 
Mixed 
symptoms are 
observable 
by others and 
represent 
a 
change 
from the 
person s usual behavior. 
C. 
For individuals whose 
symptoms meet 
full episode 
criteria 
for both 
mania 
and 
depression 
simultaneously, 
the 
diagnosis should 
be 
manic episode, 
with 
mixed 
features. 
D. 
The 
mixed 
symptoms are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication 
or other treatment). 
Note: 
Mixed 
features associated 
with 
a 
major depressive 
episode 
have 
been 
found 
to 
be 
a 
significant 
risk factor for the 
development 
of 
bipolar I 
or bipolar II 
disorder. 
As a 
result, 
it 
is clinically useful to 
note 
the 
presence 
of 
this specifier 
for treatment 
planning 
and 
monitoring 
of 
response 
to 
treatment. 


With 
rapid 
cycling: 
Presence 
of 
at 
least 
four mood 
episodes in 
the 
previous 12 
months that 
meet 
the 
criteria 
for manic, 
hypomanic, 
or major depressive 
episode 
in 
bipolar I 
disorder or that 
meet 
the 
criteria 
for hypomanic or major depressive 



episode 
in 
bipolar II 
disorder. 
Note: 
Episodes are 
demarcated 
by either partial or full remissions of 
at 
least 
2 


months or a 
switch 
to 
an 
episode 
of 
the 
opposite 
polarity (e.g., 
major 
depressive 
episode 
to 
manic episode). 
Note: 
The 
essential feature 
of 
a 
rapid-cycling 
bipolar disorder is the 


occurrence 
of 
at 
least 
four mood 
episodes during 
the 
previous 12 
months. 
These 
episodes can 
occur in 
any combination 
and 
order. 
The 
episodes must 
meet 
both 
the 
duration 
and 
the 
symptom number criteria 
for a 
major 
depressive, 
manic, 
or hypomanic episode 
and 
must 
be 
demarcated 
by either a 
period 
of 
full remission 
or a 
switch 
to 
an 
episode 
of 
the 
opposite 
polarity. 
Manic and 
hypomanic episodes are 
counted 
as being 
on 
the 
same 
pole. 
Except 
for the 
fact 
that 
they occur more 
frequently, 
the 
episodes that 
occur in 
a 
rapid-cycling 
pattern 
are 
no 
different 
from those 
that 
occur in 
a 
non-rapidcycling 
pattern. 
Mood 
episodes that 
count 
toward 
defining 
a 
rapid-cycling 
pattern 
exclude 
those 
episodes directly caused 
by a 
substance 
(e.g., 
cocaine, 
corticosteroids) or another medical condition. 


With 
melancholic 
features: 


A. 
One 
of 
the 
following 
is present 
during 
the 
most 
severe 
period 
of 
the 
current 
major depressive 
episode 
(or the 
most 
recent 
major depressive 
episode 
if 
bipolar I 
or bipolar II 
disorder is currently in 
partial or full remission): 
1. 
Loss of 
pleasure 
in 
all, 
or almost 
all, 
activities. 
2. 
Lack of 
reactivity to 
usually pleasurable 
stimuli (does not 
feel much 
better, 
even 
temporarily, 
when 
something 
good 
happens). 
B. 
Three 
(or more) of 
the 
following: 
1. 
A 
distinct 
quality of 
depressed 
mood 
characterized 
by profound 
despondency, 
despair, 
and/or moroseness or by so-called 
empty mood. 
2. 
Depression 
that 
is regularly worse 
in 
the 
morning. 
172 


3. 
Early-morning 
awakening 
(i.e., 
at 
least 
2 
hours before 
usual awakening). 
4. 
Marked 
psychomotor agitation 
or retardation. 
5. 
Significant 
anorexia 
or weight 
loss. 
6. 
Excessive 
or inappropriate 
guilt. 
Note: 
The 
specifier  with 
melancholic features  is applied 
if 
these 
features 
are 
present 
at 
the 
most 
severe 
stage 
of 
the 
episode. 
There 
is a 
near-
complete 
absence 
of 
the 
capacity for pleasure, 
not 
merely a 
diminution. 
A 
guideline 
for evaluating 
the 
lack of 
reactivity of 
mood 
is that 
even 
highly 
desired 
events are 
not 
associated 
with 
marked 
brightening 
of 
mood. 
Either 
mood 
does not 
brighten 
at 
all, 
or it 
brightens only partially (e.g., 
up 
to 
20%  
40% of 
normal for only minutes at 
a 
time). 
The 
 distinct 
quality  of 
mood 



that 
is characteristic of 
the 
 with 
melancholic features  specifier is 
experienced 
as qualitatively different 
from that 
during 
a 
nonmelancholic 
depressive 
episode. 
A 
depressed 
mood 
that 
is described 
as merely more 
severe, 
longer lasting, 
or present 
without 
a 
reason 
is not 
considered 
distinct 
in 
quality. 
Psychomotor changes are 
nearly always present 
and 
are 
observable 
by others.

 Melancholic features exhibit 
only a 
modest 
tendency to 
repeat 
across 
episodes in 
the 
same 
individual. 
They are 
more 
frequent 
in 
inpatients, 
as 
opposed 
to 
outpatients; 
are 
less likely to 
occur in 
milder than 
in 
more 
severe 
major depressive 
episodes; 
and 
are 
more 
likely to 
occur in 
individuals with 
psychotic features. 


With 
atypical 
features: 
This specifier is applied 
when 
these 
features predominate 


during 
the 
majority of 
days of 
the 
current 
major depressive 
episode 
(or the 
most 


recent 
major depressive 
episode 
if 
bipolar I 
or bipolar II 
disorder is currently in 


partial or full remission). 


A. 
Mood 
reactivity (i.e., 
mood 
brightens in 
response 
to 
actual or potential positive 
events). 
B. 
Two 
(or more) of 
the 
following: 
1. 
Significant 
weight 
gain 
or increase 
in 
appetite. 
2. 
Hypersomnia. 
3. 
Leaden 
paralysis (i.e., 
heavy, 
leaden 
feelings in 
arms or legs). 
4. 
A 
long-standing 
pattern 
of 
interpersonal rejection 
sensitivity (not 
limited 
to 
episodes of 
mood 
disturbance) that 
results in 
significant 
social or 
occupational impairment. 
C. 
Criteria 
are 
not 
met 
for  with 
melancholic features  or  with 
catatonia  during 
the 
same 
episode. 
Note: 
 Atypical depression  has historical significance 
(i.e., 
atypical in 
contradistinction 
to 
the 
more 
classical agitated, 
 endogenous  presentations of 
depression 
that 
were 
the 
norm when 
depression 
was rarely diagnosed 
in 
outpatients and 
almost 
never in 
adolescents or younger adults) and 
today 
does not 
connote 
an 
uncommon 
or unusual clinical presentation 
as the 
term 
might 
imply.

 Mood 
reactivity is the 
capacity to 
be 
cheered 
up 
when 
presented 
with 
positive 
events (e.g., 
a 
visit 
from children, 
compliments from others). 
Mood 
may become 
euthymic (not 
sad) even 
for extended 
periods of 
time 
if 
the 
external circumstances remain 
favorable. 
Increased 
appetite 
may be 
manifested 
by an 
obvious increase 
in 
food 
intake 
or by weight 
gain. 
Hypersomnia 
may include 
either an 
extended 
period 
of 
nighttime 
sleep 
or 
daytime 
napping 
that 
totals at 
least 
10 
hours of 
sleep 
per day (or at 
least 
2 
hours more 
than 
when 
not 
depressed). 
Leaden 
paralysis is defined 
as feeling 
heavy, 
leaden, 
or weighted 
down, 
usually in 
the 
arms or legs. 
This sensation 
is 
generally present 
for at 
least 
an 
hour a 
day but 
often 
lasts for many 



173 


hours at 
a 
time. 
Unlike 
the 
other atypical features, 
pathological sensitivity to 
perceived 
interpersonal rejection 
is a 
trait 
that 
has an 
early onset 
and 
persists 
throughout 
most 
of 
adult 
life. 
Rejection 
sensitivity occurs both 
when 
the 
person 
is and 
is not 
depressed, 
though 
it 
may be 
exacerbated 
during 
depressive 
periods. 


With 
psychotic 
features: 
Delusions or hallucinations are 
present 
at 
any time 
in 
the 
current 
manic or major depressive 
episode 
in 
bipolar I 
disorder (or the 
most 
recent 
manic or major depressive 
episode 
if 
bipolar I 
disorder is currently in 
partial or full remission) or in 
the 
current 
major depressive 
episode 
in 
bipolar II 
disorder (or the 
most 
recent 
major depressive 
episode 
if 
bipolar II 
disorder is 
currently in 
partial or full remission). 
If 
psychotic features are 
present, 
specify 
if 
mood-congruent 
or mood-incongruent: 


When 
applied 
to 
current 
or most 
recent 
manic episode 
(in 
bipolar I 
disorder): 


With 
mood-congruent psychotic 
features: 
The 
content 
of 
all delusions 
and 
hallucinations is consistent 
with 
the 
typical manic themes of 
grandiosity, 
invulnerability, 
etc., 
but 
may also 
include 
themes of 
suspiciousness or 
paranoia, 
especially with 
respect 
to 
others  doubts about 
the 
individual s 
capacities, 
accomplishments, 
and 
so 
forth. 


With 
mood-incongruent psychotic 
features: 
The 
content 
of 
the 
delusions 
and 
hallucinations does not 
involve 
typical manic themes as described 
above, 
or the 
content 
is a 
mixture 
of 
mood-incongruent 
and 
mood-congruent 
themes. 


When 
applied 
to 
current 
or most 
recent 
major depressive 
episode 
(in 
bipolar I 
disorder or bipolar II 
disorder): 


With 
mood-congruent psychotic 
features: 
The 
content 
of 
all delusions 
and 
hallucinations is consistent 
with 
the 
typical depressive 
themes of 
personal inadequacy, 
guilt, 
disease, 
death, 
nihilism, 
or deserved 
punishment. 


With 
mood-incongruent psychotic 
features: 
The 
content 
of 
the 
delusions 
and 
hallucinations does not 
involve 
typical depressive 
themes of 
personal 
inadequacy, 
guilt, 
disease, 
death, 
nihilism, 
or deserved 
punishment, 
or the 
content 
is a 
mixture 
of 
mood-incongruent 
and 
mood-congruent 
themes. 


With 
catatonia: 
This specifier is applied 
to 
the 
current 
manic or major 
depressive 
episode 
in 
bipolar I 
disorder (or the 
most 
recent 
manic or major 
depressive 
episode 
if 
bipolar I 
disorder is currently in 
partial or full remission) 
or to 
the 
current 
major depressive 
episode 
in 
bipolar II 
disorder (or the 
most 
recent 
major depressive 
episode 
if 
bipolar II 
disorder is currently in 
partial or 
full remission) if 
catatonic features are 
present 
during 
most 
of 
the 
episode. 
See 
criteria 
for catatonia 
associated 
with 
a 
mental disorder in 
the 
chapter 
 Schizophrenia 
Spectrum and 
Other Psychotic Disorders.  



 
 
 
 
177 



Depressive Disorders 


Depressive disorders 
include disruptive mood dysregulation disorder, major 
depressive disorder (including major depressive episode), persistent 
depressive disorder, 
premenstrual 
dysphoric disorder, substance/medication-induced depressive disorder, depressive 
disorder due to another medical 
condition, other specified depressive disorder, and unspecified 
depressive disorder. The common feature of all 
of these disorders is the presence of sad, empty, 
or irritable mood, accompanied by related changes that 
significantly affect 
the individual s 
capacity to function (e.g., somatic and cognitive changes in major depressive disorder and 
persistent 
depressive disorder). What 
differs among them 
are issues of duration, timing, or 
presumed etiology. 


In order to address concerns in the United States and, increasingly, internationally about 
the 
potential 
for the overdiagnosis and treatment 
of bipolar disorder in children, a new diagnosis, 
disruptive mood dysregulation disorder, referring to the presentation of children with persistent 
irritability and frequent 
episodes of extreme behavioral 
dyscontrol, is added to the depressive 
disorders for children up to 12 years of age. Its placement 
in this chapter reflects the finding that 
children with this symptom 
pattern typically develop unipolar depressive disorders or anxiety 
disorders, rather than bipolar disorders, as they mature into adolescence and adulthood. 


Major depressive disorder represents the classic condition in this group of disorders. It 
is 
characterized by discrete episodes of at 
least 
2 weeks  duration (although most 
episodes last 
considerably longer) involving clear-cut 
changes in affect, cognition, and neurovegetative 
functions and interepisode remissions. A diagnosis based on a single episode is possible, 
although the disorder is a recurrent 
one in the majority of cases. Careful 
consideration should be 
given to the delineation of normal 
sadness and grief from 
a major depressive episode. 
Bereavement 
may induce great 
suffering, but 
it 
does not 
typically induce an episode of major 
depressive disorder. When they do occur together, the depressive symptoms and functional 
impairment 
tend to be more severe and the prognosis is worse compared with bereavement 
that 
is not 
accompanied by major depressive disorder. Bereavement-related major depressive 
episodes tend to occur in persons with other vulnerabilities to depressive disorders. 


A more chronic form 
of depression, persistent 
depressive disorder, can be diagnosed when 
the mood disturbance continues for at 
least 
2 years in adults or 1 year in children. This diagnosis, 
new in DSM-5, includes the DSM-IV diagnostic categories of chronic major depression and 
dysthymia. 


After careful 
scientific review of the evidence, premenstrual 
dysphoric disorder has been 
moved from 
an appendix of DSM-IV ( Criteria Sets and Axes Provided for Further Study ) to 
Section II of DSM-5. Almost 
20 years of additional 
research on this condition has confirmed a 
specific and treatment-responsive form 
of depressive disorder that 
begins sometime following 
ovulation and remits within a few days of menses and has a marked impact on functioning. 


A large number of substances of abuse, some prescribed medications, and several 
medical 



conditions can be associated with depression-like phenomena. This fact 
is recognized in the 
diagnoses of substance/medication-induced depressive disorder and depressive disorder due to 
another medical condition. 


178 


Disruptive Mood 
Dysregulation 
Disorder 


Diagnostic Criteria 
F34.81 


A. 
Severe 
recurrent 
temper outbursts manifested 
verbally (e.g., 
verbal rages) 
and/or behaviorally (e.g., 
physical aggression 
toward 
people 
or property) that 
are 
grossly out 
of 
proportion 
in 
intensity or duration 
to 
the 
situation 
or provocation. 
B. 
The 
temper outbursts are 
inconsistent 
with 
developmental level. 
C. 
The 
temper outbursts occur, 
on 
average, 
three 
or more 
times per week. 
D. 
The 
mood 
between 
temper outbursts is persistently irritable 
or angry most 
of 
the 
day, 
nearly every day, 
and 
is observable 
by others (e.g., 
parents, 
teachers, 
peers). 
E. 
Criteria 
A D have 
been 
present 
for 12 
or more 
months. 
Throughout 
that 
time, 
the 
individual has not 
had 
a 
period 
lasting 
3 
or more 
consecutive 
months without 
all of 
the 
symptoms in 
Criteria 
A D. 
F. 
Criteria 
A 
and 
D are 
present 
in 
at 
least 
two 
of 
three 
settings (i.e., 
at 
home, 
at 
school, 
with 
peers) and 
are 
severe 
in 
at 
least 
one 
of 
these. 
G. 
The 
diagnosis should 
not 
be 
made 
for the 
first 
time 
before 
age 
6 
years or after 
age 
18 
years. 
H. 
By history or observation, 
the 
age 
at 
onset 
of 
Criteria 
A E 
is before 
10 
years. 
I. 
There 
has never been 
a 
distinct 
period 
lasting 
more 
than 
1 
day during 
which 
the 
full symptom criteria, 
except 
duration, 
for a 
manic or hypomanic episode 
have 
been 
met. 
Note: 
Developmentally appropriate 
mood 
elevation, 
such 
as occurs in 
the 
context 
of 
a 
highly positive 
event 
or its anticipation, 
should 
not 
be 
considered 
as 
a 
symptom of 
mania 
or hypomania. 


J. 
The 
behaviors do 
not 
occur exclusively during 
an 
episode 
of 
major depressive 
disorder and 
are 
not 
better explained 
by another mental disorder (e.g., 
autism 
spectrum disorder, 
posttraumatic stress disorder, 
separation 
anxiety disorder, 
persistent 
depressive 
disorder). 
Note: 
This diagnosis cannot 
coexist 
with 
oppositional defiant 
disorder, 
intermittent 
explosive 
disorder, 
or bipolar disorder, 
though 
it 
can 
coexist 
with 
others, 
including 
major depressive 
disorder, 
attention-deficit/hyperactivity 
disorder, 
conduct 
disorder, 
and 
substance 
use 
disorders. 
Individuals whose 
symptoms meet 
criteria 
for both 
disruptive 
mood 
dysregulation 
disorder and 



oppositional defiant 
disorder should 
only be 
given 
the 
diagnosis of 
disruptive 
mood 
dysregulation 
disorder. 
If 
an 
individual has ever experienced 
a 
manic or 
hypomanic episode, 
the 
diagnosis of 
disruptive 
mood 
dysregulation 
disorder 
should 
not 
be 
assigned. 


K. 
The 
symptoms are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
or 
another medical or neurological condition. 
Diagnostic Features 


The core feature of disruptive mood dysregulation disorder is chronic severe, persistent 
irritability. This severe irritability has two prominent 
clinical 
manifestations, the first 
of which is 
frequent 
temper outbursts. These outbursts typically occur in response to frustration and can be 
verbal 
or behavioral 
(the latter in the form 
of aggression against 
property, self, or others). They 
must 
occur frequently (i.e., on average, three or more times per week) (Criterion C) over at 
least 
1 year in at 
least 
two settings (Criteria E 
and F), such as in the home and at 
school, and they must 
be developmentally inappropriate (Criterion B). The second manifestation of severe irritability 
consists of chronic, persistently irritable or angry mood that 
is present 
between the severe temper 
outbursts. This irritable or angry mood must 
be characteristic of the child, being present 
most 
of 
the day, nearly every day, and noticeable by others in the child s environment (Criterion D). 


179 


The clinical 
presentation of disruptive mood dysregulation disorder must 
be carefully 
distinguished from 
presentations of other, related conditions, particularly pediatric bipolar 
disorder. In fact, disruptive mood dysregulation disorder was added to DSM-5 to address the 
considerable concern about 
the appropriate classification and treatment 
of children who present 
with chronic, persistent 
irritability relative to children who present 
with classic (i.e., episodic) 
bipolar disorder. 


Some researchers view severe, nonepisodic irritability as characteristic of bipolar disorder in 
children, although both DSM-IV and DSM-5 require that 
both children and adults have distinct 
episodes of mania or hypomania to qualify for the diagnosis of bipolar I disorder. During the 
latter decades of the twentieth century, this contention by researchers that 
severe, nonepisodic 
irritability is a manifestation of pediatric mania coincided with an upsurge in the rates at 
which 
clinicians assigned the diagnosis of bipolar disorder to their pediatric patients. This sharp 
increase in rates appears to be attributable to clinicians combining at 
least 
two clinical 
presentations into a single category. That 
is, both classic, episodic presentations of mania and 
nonepisodic presentations of severe irritability have been labeled as bipolar disorder in children. 
In DSM-5, the term 
bipolar disorder 
is explicitly reserved for episodic presentations of bipolar 
symptoms. DSM-IV did not 
include a diagnosis designed to capture youths whose hallmark 
symptoms consisted of very severe, nonepisodic irritability, whereas DSM-5, with the inclusion 
of disruptive mood dysregulation disorder, provides a distinct category for such presentations. 


Prevalence 


Disruptive mood dysregulation disorder is common among children presenting to pediatric 



mental 
health clinics. Prevalence estimates of the disorder in the community are unclear. In a 
population-based cohort 
study of Brazilian 11-year-olds that 
used a specific module for 
disruptive mood dysregulation disorder, the prevalence was 2.5%. 


Consistent 
gender differences in prevalence have not 
been reported in population samples, 
although clinic samples report 
a male preponderance. For example, up to 80% of children 
presenting to clinics in Turkey with features of disruptive mood dysregulation disorder in a chart 
review were boys. Data suggest 
that 
the diagnosis may be more common in younger age groups 
(e.g., 8.2% in a community sample of 6-year-olds in the United States). 


Development and Course 


The onset 
of disruptive mood dysregulation disorder must 
be before age 10 years, and the 
diagnosis should not 
be applied to children with a developmental 
age of younger than 6 years. It 
is unknown whether the condition presents only in this age-delimited fashion. Because the 
symptoms of disruptive mood dysregulation disorder are likely to change as children mature, use 
of the diagnosis should be restricted to age groups similar to those in which validity has been 
established (6 18 years). Approximately half of children with disruptive mood dysregulation 
disorder living in a predominantly rural 
area in a large U.S. study continue to have symptoms 
that 
meet 
criteria for the condition 1 year later, although those children whose symptoms no 
longer meet 
the threshold for the diagnosis often have persistent, clinically impairing irritability. 
Rates of conversion from 
severe, nonepisodic irritability to bipolar disorder are very low. 
Instead, children with disruptive mood dysregulation disorder are at 
increased risk to develop 
unipolar depressive and/or anxiety disorders in adulthood. 


Risk and Prognostic Factors 


Temperamental. 
Children with chronic irritability typically exhibit 
complicated psychiatric 
histories. In such children, a relatively extensive history of chronic irritability is common, 
typically manifesting before full 
criteria for the syndrome are met. Such prediagnostic 
presentations may have qualified for a diagnosis of oppositional defiant 


180 


disorder. Many children with disruptive mood dysregulation disorder have symptoms that 
also 
meet 
criteria for attention-deficit/hyperactivity disorder (ADHD) and for an anxiety disorder, 
with such diagnoses often being present 
from 
a relatively early age. For some children, the 
criteria for major depressive disorder may also be met. 


Environmental. 
Factors associated with disrupted family life, such as psychological 
abuse or 
neglect, parental 
psychiatric disorder, limited parental 
education, single-parent 
household, early 
trauma, death of a parent, parental 
grief, divorce, and malnutrition (e.g., vitamin deficiency), are 
associated with the core behaviors of disruptive mood dysregulation disorder. 


Genetic 
and 
physiological. 
Data suggest 
that 
a family history of depression may be a risk factor for 
disruptive mood dysregulation disorder. Consistent 
with this, twin data suggest 
that 
the 
association between early irritability and later unipolar depression and anxiety may be, in part, 
genetically mediated. 


Compared with children with pediatric bipolar disorder or other mental 
illnesses, those with 



disruptive mood dysregulation disorder exhibit 
both commonalities and differences in 
information-processing deficits. For example, face-emotion labeling deficits, as well 
as perturbed 
decision-making and cognitive control, are present 
in children with bipolar disorder as well 
as 
those with disruptive mood dysregulation disorder. Importantly, however, the same behavioral 
deficit 
may be associated with different 
patterns of neural 
dysfunction. There is also evidence for 
disorder-specific dysfunction, such as during tasks assessing attention deployment 
in response to 
emotional 
stimuli, which has demonstrated unique signs of dysfunction in children with chronic 
irritability. 


Culture-Related Diagnostic Issues 


Culture-related data on disruptive mood dysregulation disorder are limited. However, 
sociocultural 
factors affect 
the presentation of core psychological 
features of the disorder, 
including impulsivity as well 
as emotion, reward, threat, and behavior dysregulation, especially 
in settings characterized by severe social 
disruption, such as postconflict 
zones or communities 
affected by long-standing racism 
and discrimination. It 
is important 
to distinguish disruptive 
mood dysregulation disorder from 
adaptive responses to adversity that 
are context-dependent 
and 
transitory. 


Sex- and Gender-Related Diagnostic Issues 


There is some evidence from 
twin studies that 
while irritability has a strong genetic component 
in both sexes, patterns differ for boys and girls. For boys, genetic factors appear to account 
for an 
increasing amount 
of the variance of the phenotype of irritability throughout 
childhood. While 
genetic factors account 
for a large proportion of the variance of the irritability phenotype in 
school-age girls, this decreases into adolescence and young adulthood, with environmental 
influences playing a greater role. How this genetic risk for irritability translates into risk and 
prognosis for disruptive mood dysregulation disorder, per se, is not yet known. 


Functional 
Consequences of Disruptive Mood Dysregulation Disorder 


Chronic, severe irritability, such as is seen in disruptive mood dysregulation disorder, is 
associated with marked disruption in a child s family and peer relationships, as well 
as in school 
performance. Because of their extremely low frustration tolerance, such children generally have 
difficulty succeeding in school; 
they are often unable to participate in the activities typically 
enjoyed by healthy children; 
their family life is severely disrupted by their outbursts and 
irritability; 
and they have trouble initiating or sustaining friendships. Levels of dysfunction in 
children with bipolar disorder and disruptive mood 


181 


dysregulation disorder are generally comparable. Both conditions cause severe disruption in the 
lives of the affected individual 
and his or her family. In both disruptive mood dysregulation 
disorder and pediatric bipolar disorder, aggression and psychiatric hospitalization are common. 


Differential 
Diagnosis 



Because chronically irritable children and adolescents typically present 
with complex histories, 
the diagnosis of disruptive mood dysregulation disorder must 
be made while considering the 
presence or absence of multiple other conditions. Despite the need to consider many other 
syndromes, differentiation of disruptive mood dysregulation disorder from 
bipolar disorder and 
oppositional defiant disorder requires particularly careful assessment. 


Bipolar disorders. 
The central 
feature differentiating disruptive mood dysregulation disorder and 
bipolar disorders in children involves the longitudinal 
course of the core symptoms. In children, 
as in adults, bipolar I disorder and bipolar II disorder manifest 
as an episodic illness with discrete 
episodes of mood perturbation that 
can be differentiated from 
the child s typical 
presentation. 
The mood perturbation that 
occurs during a manic episode is distinctly different 
from 
the child s 
usual 
mood. In addition, during a manic episode, the change in mood must 
be accompanied by 
the onset, or worsening, of associated cognitive, behavioral, and physical 
symptoms (e.g., 
distractibility, increased goal-directed activity), which are also present 
to a degree that 
is 
distinctly different 
from 
the child s usual 
baseline. Thus, in the case of a manic episode, parents 
(and, depending on developmental 
level, children) should be able to identify a distinct 
time 
period during which the child s mood and behavior were markedly different 
from 
usual. In 
contrast, the irritability of disruptive mood dysregulation disorder is persistent 
and is present 
over many months; 
while it 
may wax and wane to a certain degree, severe irritability is 
characteristic of the child with disruptive mood dysregulation disorder. Thus, while bipolar 
disorders are episodic conditions, disruptive mood dysregulation disorder is not. In fact, the 
diagnosis of disruptive mood dysregulation disorder cannot 
be assigned to a child who has ever 
experienced a full-duration hypomanic or manic episode (irritable or euphoric) or who has ever 
had a manic or hypomanic episode lasting more than 1 day. Another central 
differentiating 
feature between bipolar disorders and disruptive mood dysregulation disorder is the presence of 
elevated or expansive mood and grandiosity. These symptoms are common features of mania but 
are not characteristic of disruptive mood dysregulation disorder. 


Oppositional 
defiant 
disorder. 
While symptoms of oppositional 
defiant 
disorder typically do occur 
in children with disruptive mood dysregulation disorder, mood symptoms of disruptive mood 
dysregulation disorder are relatively rare in children with oppositional 
defiant 
disorder. The key 
features that 
warrant 
the diagnosis of disruptive mood dysregulation disorder in children whose 
symptoms also meet 
criteria for oppositional 
defiant 
disorder are the presence of severe and 
frequently recurrent 
outbursts and a persistent 
disruption in mood between outbursts. In addition, 
the diagnosis of disruptive mood dysregulation disorder requires severe impairment 
in at 
least 
one setting (i.e., home, school, or among peers) and mild to moderate impairment 
in a second 
setting. For this reason, while most 
children whose symptoms meet 
criteria for disruptive mood 
dysregulation disorder will 
also have a presentation that 
meets criteria for oppositional 
defiant 
disorder, the reverse is not 
the case. That 
is, in only approximately 15% of individuals with 
oppositional 
defiant 
disorder would criteria for disruptive mood dysregulation disorder be met. 
Moreover, even for children in whom 
criteria for both disorders are met, only the diagnosis of 
disruptive mood dysregulation disorder should be made. Finally, both the prominent 
mood 
symptoms in disruptive mood dysregulation disorder and the high risk for depressive and anxiety 
disorders in follow-up studies justify placement 
of disruptive mood dysregulation disorder 
among the depressive disorders in DSM-5. (Oppositional 
defiant 
disorder is included in the 
chapter  Disruptive, Impulse-Control, and Conduct 



182 


Disorders. ) This reflects the more prominent 
mood component 
among individuals with 
disruptive mood dysregulation disorder, as compared with individuals with oppositional 
defiant 
disorder. Nevertheless, it 
also should be noted that 
disruptive mood dysregulation disorder 
appears to carry a high risk for behavioral problems as well as mood problems. 


Attention-deficit/hyperactivity 
disorder, 
major depressive 
disorder, 
anxiety 
disorders, 
and 
autism spectrum disorder. 


Unlike children diagnosed with bipolar disorder or oppositional 
defiant 
disorder for whom 
a 
diagnosis of disruptive mood dysregulation disorder cannot 
be given even if the symptoms meet 
diagnostic criteria for that 
disorder children whose symptoms meet 
criteria for disruptive mood 
dysregulation disorder also can receive a comorbid diagnosis of ADHD, major depressive 
disorder, and/or anxiety disorder. However, children whose irritability is present 
only in the 
context 
of a major depressive episode or persistent 
depressive disorder should receive one of 
those diagnoses rather than disruptive mood dysregulation disorder. Children with disruptive 
mood dysregulation disorder may have symptoms that 
also meet 
criteria for an anxiety disorder 
and can receive both diagnoses, but 
children whose irritability is manifest 
only in the context 
of 
exacerbation of an anxiety disorder should receive the relevant 
anxiety disorder diagnosis rather 
than disruptive mood dysregulation disorder. In addition, children with autism 
spectrum 
disorders frequently present 
with temper outbursts when, for example, their routines are 
disturbed. In that 
instance, the temper outbursts would be considered secondary to the autism 
spectrum 
disorder, and the child should not 
receive the diagnosis of disruptive mood 
dysregulation disorder. 


Intermittent 
explosive 
disorder. 
Children with symptoms suggestive of intermittent 
explosive 
disorder present 
with instances of severe temper outbursts, much like children with disruptive 
mood dysregulation disorder. However, unlike disruptive mood dysregulation disorder, 
intermittent 
explosive disorder does not 
require the individual s mood to be persistently irritable 
or angry between outbursts. In addition, a diagnosis of intermittent 
explosive disorder involving 
verbal 
aggression or physical 
aggression that 
does not 
result 
in damage to property or physical 
injury to animals or other individuals occurring at 
least 
twice weekly can be made after only 3 
months of symptoms, in contrast 
to the 12-month requirement 
for disruptive mood dysregulation 
disorder. Thus, these two diagnoses should not 
be made in the same child. For children with 
outbursts and intercurrent, persistent 
irritability, only the diagnosis of disruptive mood 
dysregulation disorder should be made. 


Comorbidity 


Rates of comorbidity in disruptive mood dysregulation disorder are extremely high. It 
is rare to 
find individuals whose symptoms meet 
criteria for disruptive mood dysregulation disorder alone. 
Comorbidity between disruptive mood dysregulation disorder and other DSM-defined 
syndromes appears higher than for many other pediatric mental 
illnesses; 
the strongest 
overlap is 
with oppositional 
defiant 
disorder. Not 
only is the overall 
rate of comorbidity high in disruptive 
mood dysregulation disorder, but 
also the range of comorbid illnesses appears particularly 
diverse. These children typically present 
to the clinic with a wide range of disruptive behavior, 
mood, anxiety, and even autism 
spectrum 
symptoms and diagnoses. However, children with 



disruptive mood dysregulation disorder should not 
have symptoms that 
meet 
criteria for bipolar 
disorder, as in that 
context, only the bipolar disorder diagnosis should be made. If children have 
symptoms that 
meet 
criteria for oppositional 
defiant 
disorder or intermittent 
explosive disorder 
and 
disruptive mood dysregulation disorder, only the diagnosis of disruptive mood dysregulation 
disorder should be assigned. Also, as noted earlier, the diagnosis of disruptive mood 
dysregulation disorder should not 
be assigned if the symptoms occur only in an anxiety-
provoking context, when the routines of a child with autism 
spectrum 
disorder or obsessive-
compulsive disorder are disturbed, or in the context of a major depressive episode. 


183 


Major Depressive Disorder 


Diagnostic Criteria 


A. 
Five 
(or more) of 
the 
following 
symptoms have 
been 
present 
during 
the 
same 
2week 
period 
and 
represent 
a 
change 
from previous functioning; 
at 
least 
one 
of 
the 
symptoms is either (1) depressed 
mood 
or (2) loss of 
interest 
or pleasure. 
Note: 
Do 
not 
include 
symptoms that 
are 
clearly attributable 
to 
another medical 
condition. 


1. 
Depressed 
mood 
most 
of 
the 
day, 
nearly every day, 
as indicated 
by either 
subjective 
report 
(e.g., 
feels sad, 
empty, 
hopeless) or observation 
made 
by 
others (e.g., 
appears tearful). 
(Note: 
In 
children 
and 
adolescents, 
can 
be 
irritable 
mood.) 
2. 
Markedly diminished 
interest 
or pleasure 
in 
all, 
or almost 
all, 
activities most 
of 
the 
day, 
nearly every day (as indicated 
by either subjective 
account 
or 
observation). 
3. 
Significant 
weight 
loss when 
not 
dieting 
or weight 
gain 
(e.g., 
a 
change 
of 
more 
than 
5% of 
body weight 
in 
a 
month), 
or decrease 
or increase 
in 
appetite 
nearly every day. 
(Note: 
In 
children, 
consider failure 
to 
make 
expected 
weight 
gain.) 
4. 
Insomnia 
or hypersomnia 
nearly every day. 
5. 
Psychomotor agitation 
or retardation 
nearly every day (observable 
by others, 
not 
merely subjective 
feelings of 
restlessness or being 
slowed 
down). 
6. 
Fatigue 
or loss of 
energy nearly every day. 
7. 
Feelings of 
worthlessness or excessive 
or inappropriate 
guilt 
(which 
may be 
delusional) nearly every day (not 
merely self-reproach 
or guilt 
about 
being 
sick). 
8. 
Diminished 
ability to 
think or concentrate, 
or indecisiveness, 
nearly every day 
(either by subjective 
account 
or as observed 
by others). 
9. 
Recurrent 
thoughts of 
death 
(not 
just 
fear of 
dying), 
recurrent 
suicidal ideation 

without 
a 
specific plan, 
or a 
suicide 
attempt 
or a 
specific plan 
for committing 
suicide. 


B. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
C. 
The 
episode 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
or 
another medical condition. 
Note: 
Criteria 
A C represent 
a 
major depressive 
episode. 
Note: 
Responses to 
a 
significant 
loss (e.g., 
bereavement, 
financial ruin, 
losses 
from a 
natural disaster, 
a 
serious medical illness or disability) may include 
the 
feelings of 
intense 
sadness, 
rumination 
about 
the 
loss, 
insomnia, 
poor appetite, 
and 
weight 
loss noted 
in 
Criterion 
A, 
which 
may resemble 
a 
depressive 
episode. 
Although 
such 
symptoms may be 
understandable 
or considered 
appropriate 
to 
the 
loss, 
the 
presence 
of 
a 
major depressive 
episode 
in 
addition 
to 
the 
normal 
response 
to 
a 
significant 
loss should 
also 
be 
carefully considered. 
This decision 
inevitably requires the 
exercise 
of 
clinical judgment 
based 
on 
the 
individual s 
history and 
the 
cultural norms for the 
expression 
of 
distress in 
the 
context 
of 
loss.1 


D. 
At 
least 
one 
major depressive 
episode 
is not 
better explained 
by schizoaffective 
disorder and 
is not 
superimposed 
on 
schizophrenia, 
schizophreniform disorder, 
delusional disorder, 
or other specified 
and 
unspecified 
schizophrenia 
spectrum 
and 
other psychotic disorders. 
E. 
There 
has never been 
a 
manic episode 
or a 
hypomanic episode. 
Note: 
This exclusion 
does not 
apply if 
all of 
the 
manic-like 
or hypomanic-like 
episodes are 
substance-induced 
or are 
attributable 
to 
the 
physiological effects of 
another medical condition. 


184 


Coding 
and 
Recording 
Procedures 


The 
diagnostic code 
for major depressive 
disorder is based 
on 
whether this is a 
single 
or recurrent 
episode, 
current 
severity, 
presence 
of 
psychotic features, 
and 
remission 
status. 
Current 
severity and 
psychotic features are 
only indicated 
if 
full 
criteria 
are 
currently met 
for a 
major depressive 
episode. 
Remission 
specifiers are 
only indicated 
if 
the 
full criteria 
are 
not 
currently met 
for a 
major depressive 
episode. 
Codes are 
as follows: 


Recurrent 
Severity/course 
specifier 
Single 
episode 
episode* 
Mild 
(p. 
214) 
F32.0 
F33.0 
Moderate 
(p. 
214) 
F32.1 
F33.1 
Severe 
(p. 
214) 
F32.2 
F33.2 
With 
psychotic features** 
(pp. 
212 213) 
F32.3 
F33.3 
In 
partial remission 
(p. 
214) 
F32.4 
F33.41 



In 
full remission 
(p. 
214) 
F32.5 
F33.42 
Unspecified 
F32.9 
F33.9 


*For 
an 
episode 
to 
be 
considered 
recurrent, 
there 
must 
be 
an 
interval of 
at 
least 
2 
consecutive 
months between 
separate 
episodes in 
which 
criteria 
are 
not 
met 
for 
a 
major 
depressive 
episode. 
The 
definitions of 
specifiers are 
found 
on 
the 
indicated 
pages. 


**If 
psychotic features are 
present, 
code 
the 
 with 
psychotic features  
specifier 
irrespective 
of 
episode 
severity. 
In 
recording 
the 
name 
of 
a 
diagnosis, 
terms should 
be 
listed 
in 
the 
following 
order: 
major depressive 
disorder, 
single 
or recurrent 
episode, 
severity/psychotic/remission 
specifiers, 
followed 
by as many of 
the 
following 
specifiers without 
codes that 
apply to 
the 
current 
episode 
(or the 
most 
recent 
episode 
if 
the 
major depressive 
disorder is in 
partial or full remission). 
Note: 
The 
specifier  with 
seasonal pattern  describes the 
pattern 
of 
recurrent 
major depressive 
episodes. 
Specify 
if: 


With 
anxious 
distress 
(pp. 
210 211) 


With 
mixed 
features 
(p. 
211) 


With 
melancholic 
features 
(pp. 
211 212) 


185 


With 
atypical 
features 
(p. 
212) 
With 
mood-congruent psychotic 
features 
(p. 
213) 
With 
mood-incongruent psychotic 
features 
(p. 
213) 
With 
catatonia 
(p. 
213). 
Coding 
note: 
Use 
additional code 
F06.1. 
With 
peripartum onset 
(p. 
213) 
With 
seasonal 
pattern 
(applies to 
pattern 
of 
recurrent 
major depressive 


episodes) (p. 
214) 


Diagnostic Features 


Major depressive disorder is defined by the presence of at 
least 
one major depressive episode 
occurring in the absence of a history of manic or hypomanic episodes. The essential 
feature of a 
major depressive episode is a period lasting at 
least 
2 weeks during which there is either 
depressed mood or the loss of interest 
or pleasure in all 
or nearly all 
activities for most 
of the day 
nearly every day (Criterion A). The individual 
must 
also experience at 
least 
four additional 
symptoms during the same 2-week period, drawn from 
a list 
that 
includes changes in appetite or 
weight, sleep, and psychomotor activity; 
decreased energy; 
feelings of worthlessness or guilt; 
difficulty thinking, concentrating, or making decisions; 
or thoughts of death, suicidal 
ideation, a 
suicide attempt, or a specific plan for suicidal 
behavior. To count 
toward a diagnosis of a major 
depressive episode, a symptom 
must 
either be newly present 
or have clearly worsened compared 
with the individual s pre-episode status. Moreover, the symptoms must 
occur nearly every day, 
for at 
least 
2 consecutive weeks, with the exception of thoughts of death and suicidal 
ideation, 
which must 
be recurrent, and attempting suicide or making a specific plan, which only needs to 



occur once. The episode must 
be accompanied by clinically significant 
distress or impairment 
in 
social, occupational, or other important 
areas of functioning. For some individuals with milder 
episodes, functioning may appear to be normal 
but 
requires markedly increased effort. The 
presenting complaint 
is often insomnia or fatigue rather than depressed mood or loss of interest; 
thus, the failure to probe for accompanying depressive symptoms can result 
in underdiagnosis. 
Fatigue and sleep disturbance are present 
in a high proportion of cases; 
psychomotor 
disturbances are much less common but 
are indicative of greater overall 
severity, as is the 
presence of delusional or near-delusional guilt. 


The mood in a major depressive episode is often described by the individual 
as depressed, 
sad, hopeless, discouraged, or  down in the dumps  (Criterion A1). In some cases, sadness may 
be denied at 
first 
but 
may subsequently be elicited by interview (e.g., by pointing out 
that 
the 
individual 
looks as if he or she is about 
to cry). In some individuals who complain of feeling 
 blah,  having no feelings, or feeling anxious, the presence of a depressed mood can be inferred 
from 
the individual s facial 
expression and demeanor. Some individuals emphasize somatic 
complaints (e.g., bodily aches and pains) rather than reporting feelings of sadness. Many 
individuals report 
or exhibit 
increased irritability (e.g., persistent 
anger, a tendency to respond to 
events with angry outbursts or blaming others, an exaggerated sense of frustration over minor 
matters). In children and adolescents, an irritable or cranky mood may develop rather than a sad 
or dejected mood. This presentation should be differentiated from 
a pattern of irritability when 
frustrated. 


Diminished interest 
or pleasure in usual 
activities is nearly always present, at 
least 
to some 
degree. Individuals may report 
feeling less interested in hobbies,  not 
caring anymore,  or not 
feeling any enjoyment 
in activities that 
were previously considered pleasurable (Criterion A2). 
Family members often notice social 
withdrawal 
or neglect 
of pleasurable avocations (e.g., a 
formerly avid golfer no longer plays, a child who used to enjoy soccer finds excuses not 
to 
practice). In some individuals, there is a significant 
reduction from 
previous levels of sexual 
interest or desire. 


186 


Appetite change may involve either a reduction or an increase. Some depressed individuals 
report 
that 
they have to force themselves to eat. Others may eat 
more and may crave specific 
foods (e.g., sweets or other carbohydrates). When appetite changes are severe (in either 
direction), there may be a significant 
loss or gain in weight, or, in children, a failure to make 
expected weight gains may be noted (Criterion A3). 


Sleep disturbance may take the form 
of either difficulty sleeping or sleeping excessively 
(Criterion A4). When insomnia is present, it 
typically takes the form 
of middle insomnia (i.e., 
waking up during the night 
and then having difficulty returning to sleep) or terminal 
insomnia 
(i.e., waking too early and being unable to return to sleep). Initial 
insomnia (i.e., difficulty falling 
asleep) may also occur. Individuals who present 
with oversleeping (hypersomnia) may 
experience prolonged sleep episodes at 
night 
or increased daytime sleep. Sometimes the reason 
that the individual seeks treatment is for the disturbed sleep. 


Psychomotor changes include agitation (e.g., the inability to sit 
still, pacing, hand-wringing; 
or pulling or rubbing of the skin, clothing, or other objects) or retardation (e.g., slowed speech, 
thinking, and body movements; 
increased pauses before answering; 
speech that 
is decreased in 



volume, inflection, amount, or variety of content, or muteness) (Criterion A5). The psychomotor 
agitation or retardation must 
be severe enough to be observable by others and not 
represent 
merely subjective feelings. Individuals who display either psychomotor disturbance (i.e., 
psychomotor agitation or retardation) are likely to have histories of the other. 


Decreased energy, tiredness, and fatigue are common (Criterion A6). An individual 
may 
report 
sustained fatigue without 
physical 
exertion. Even the smallest 
tasks seem 
to require 
substantial 
effort. The efficiency with which tasks are accomplished may be reduced. For 
example, an individual 
may complain that 
washing and dressing in the morning are exhausting 
and take twice as long as usual. This symptom 
accounts for much of the impairment 
resulting 
from major depressive disorder, both during acute episodes and when remission is incomplete. 


The sense of worthlessness or guilt 
associated with a major depressive episode may include 
unrealistic negative evaluations of one s worth or guilty preoccupations or ruminations over 
minor past 
failings (Criterion A7). Such individuals often misinterpret 
neutral 
or trivial 
day-today 
events as evidence of personal 
defects and have an exaggerated sense of responsibility for 
untoward events. The sense of worthlessness or guilt 
may be of delusional 
proportions (e.g., an 
individual 
who is convinced that 
he or she is personally responsible for world poverty). Blaming 
oneself for being sick and for failing to meet 
occupational 
or interpersonal 
responsibilities as a 
result 
of the depression is very common and, unless delusional, is not 
considered sufficient 
to 
meet this criterion. 


Many individuals report 
impaired ability to think, concentrate, or make even minor decisions 
(Criterion A8). They may appear easily distracted or complain of memory difficulties. Those 
engaged in cognitively demanding pursuits are often unable to function. In children, a 
precipitous drop in grades may reflect 
poor concentration. In elderly individuals, memory 
difficulties may be the chief complaint 
and may be mistaken for early signs of a dementia 
( pseudodementia ). When the major depressive episode is successfully treated, the memory 
problems often fully abate. However, in some individuals, particularly elderly persons, a major 
depressive episode may sometimes be the initial presentation of an irreversible dementia. 


Thoughts of death, suicidal 
ideation, or suicide attempts (Criterion A9) are common. They 
may range from 
a passive wish not 
to awaken in the morning or a belief that 
others would be 
better off if the individual 
were dead, to transient 
but 
recurrent 
thoughts of dying by suicide, to a 
specific suicide plan. More severely suicidal 
individuals may have put 
their affairs in order (e.g., 
updated wills, settled debts), acquired needed materials (e.g., a rope or a gun), and chosen a 
location and time to accomplish the suicide. Motivations for suicide may include a desire to give 
up in the face of perceived insurmountable obstacles, 


187 


an intense wish to end what 
is perceived as an unending and excruciatingly painful 
emotional 
state, an inability to foresee any enjoyment 
in life, or the wish to not 
be a burden to others. The 
resolution of such thinking may be a more meaningful 
measure of diminished suicide risk than 
denial of further plans for suicide. 


The degree of impairment 
associated with a major depressive episode varies, but 
even in 
milder cases, there must 
be either clinically significant 
distress or some interference in social, 
occupational, or other important 
areas of functioning (Criterion B). If impairment 
is severe, the 
individual 
may lose the ability to function socially or occupationally. In extreme cases, the 



individual 
may be unable to perform 
minimal 
self-care (e.g., feeding and clothing self) or to 
maintain minimal personal hygiene. 


The individual s report 
of symptoms may be compromised by difficulties in concentrating, 
impaired memory, or a tendency to deny, discount, or explain away symptoms. Information from 
additional 
informants can be especially helpful 
in clarifying the course of current 
or prior major 
depressive episodes and in assessing whether there have been any manic or hypomanic episodes. 
Because major depressive episodes can begin gradually, a review of clinical 
information that 
focuses on the worst 
part 
of the current 
episode may be most 
likely to detect 
the presence of 
symptoms. 


The evaluation of the symptoms of a major depressive episode is especially difficult 
when 
they occur in an individual 
who also has another medical 
condition (e.g., cancer, stroke, 
myocardial 
infarction, diabetes, pregnancy). Some of the criterion signs and symptoms of a 
major depressive episode are identical 
to those of another medical 
condition (e.g., weight 
loss 
with untreated diabetes; 
fatigue with cancer; 
hypersomnia early in pregnancy; 
insomnia later in 
pregnancy or the postpartum). Such symptoms count 
toward a major depressive diagnosis except 
when they are clearly and fully attributable to another medical 
condition. Nonvegetative 
symptoms of dysphoria, anhedonia, guilt 
or worthlessness, impaired concentration or indecision, 
and suicidal 
thoughts should be assessed with particular care in such cases. Definitions of major 
depressive episodes that 
have been modified to include only these nonvegetative symptoms 
appear to identify nearly the same individuals as do the full criteria. 


Associated Features 


Major depressive disorder is associated with high mortality, much of which is accounted for by 
suicide; 
however, it 
is not 
the only cause. For example, depressed individuals admitted to nursing 
homes have a markedly increased likelihood of death in the first 
year. Individuals frequently 
present 
with tearfulness, irritability, brooding, obsessive rumination, anxiety, phobias, excessive 
worry over physical 
health, and complaints of pain (e.g., headaches; 
joint, abdominal, or other 
pains). In children, separation anxiety may occur. 


Although an extensive literature exists describing neuroanatomical, neuroendocrinological, 
and neurophysiological 
correlates of major depressive disorder, no laboratory test 
has yielded 
results of sufficient 
sensitivity and specificity to be used as a diagnostic tool 
for this disorder. 
Until 
recently, hypothalamic-pituitary-adrenal 
axis hyperactivity had been the most 
extensively 
investigated abnormality associated with major depressive episodes, and it 
appears to be 
associated with melancholia (a particularly severe type of depression), psychotic features, and 
risks for eventual 
suicide. Molecular studies have also implicated peripheral 
factors, including 
genetic variants in neurotrophic factors and pro-inflammatory cytokines. Additionally, 
volumetric and functional 
magnetic resonance imaging studies provide evidence for 
abnormalities in specific neural 
systems supporting emotion processing, reward seeking, and 
emotion regulation in adults with major depression. 


Prevalence 


Twelve-month prevalence of major depressive disorder in the United States is approximately 
7%, with marked differences by age group such that the prevalence in 18- to 29-year-old 



188 


individuals is threefold higher than the prevalence in individuals age 60 years or older. The most 
reproducible finding in the epidemiology of major depressive disorder has been a higher 
prevalence in females, an effect 
that 
peaks in adolescence and then stabilizes. Women experience 
approximately twofold higher rates than men, especially between menarche and menopause. 
Women report 
more atypical 
symptoms of depression characterized by hypersomnia, increased 
appetite, and leaden paralysis compared with men. 


Systematic reviews show that 
the 12-month and point 
prevalence of major depressive 
disorder vary eight- to ninefold across global 
geographic regions. In the United States, 
prevalence increased from 
2005 to 2015, with steeper rates of increase for youth compared with 
older groups. After stratification by ethnoracial 
groups, non-Hispanic Whites showed a 
significant 
increase in prevalence after adjustment 
for demographic characteristics, whereas no 
significant change in rate of depression was observed among non-Hispanic Blacks or Hispanics. 


Development and Course 


Major depressive disorder may first 
appear at 
any age, but 
the likelihood of onset 
increases 
markedly with puberty. In the United States, incidence appears to peak in the 20s; 
however, first 
onset in late life is not uncommon. 


The course of major depressive disorder is quite variable, such that 
some individuals rarely, 
if ever, experience remission (a period of 2 or more months with no symptoms, or only one or 
two symptoms to no more than a mild degree), while others experience many years with few or 
no symptoms between discrete episodes. The course of depression may reflect 
social-structural 
adversity associated with poverty, racism, and marginalization. 


It 
is important 
to distinguish individuals who present 
for treatment 
during an exacerbation of 
a chronic depressive illness from 
those whose symptoms developed recently. Chronicity of 
depressive symptoms substantially increases the likelihood of underlying personality, anxiety, 
and substance use disorders and decreases the likelihood that 
treatment 
will 
be followed by full 
symptom 
resolution. It 
is therefore useful 
to ask individuals presenting with depressive 
symptoms to identify the last 
period of at 
least 
2 months during which they were entirely free of 
depressive symptoms. Cases in which depressive symptoms are present 
for more days than not 
might warrant an additional diagnosis of persistent depressive disorder. 


Recovery from 
a major depressive episode begins within 3 months of onset 
for 40% of 
individuals with major depression and within 1 year for 80% of individuals. Recency of onset 
is 
a strong determinant 
of the likelihood of near-term 
recovery, and many individuals who have 
been depressed for only several 
months can be expected to recover spontaneously. Features 
associated with lower recovery rates, other than current 
episode duration, include psychotic 
features, prominent anxiety, personality disorders, and symptom severity. 


The risk of recurrence becomes progressively lower over time as the duration of remission 
increases. The risk is higher in individuals whose preceding episode was severe, in younger 
individuals, and in individuals who have already experienced multiple episodes. The persistence 
of even mild depressive symptoms during remission is a powerful predictor of recurrence. 


Many bipolar illnesses begin with one or more depressive episodes, and a substantial 
proportion of individuals who initially appear to have major depressive disorder will 
prove, in 



time, to instead have a bipolar disorder. This is more likely in individuals with onset 
of the 
illness in adolescence, those with psychotic features, and those with a family history of bipolar 
illness. The presence of a  with mixed features  specifier also increases the risk for future manic 
or hypomanic diagnosis. Major depressive disorder, particularly with psychotic features, may 
also transition into schizophrenia, a change that is much more frequent than the reverse. 


189 


There are no clear effects of current 
age on the course or treatment 
response of major 
depressive disorder. Some symptom 
differences exist, though, such that 
hypersomnia and 
hyperphagia are more likely in younger individuals, and melancholic symptoms, particularly 
psychomotor disturbances, are more common in older individuals. Depressions with earlier ages 
at 
onset 
are more familial 
and more likely to involve personality disturbances. The course of 
major depressive disorder within individuals does not 
generally change with aging. Mean times 
to recovery do not 
change over multiple episodes, and the likelihood of being in an episode does 
not generally increase or decrease with time. 


Risk and Prognostic Factors 


Temperamental. 
Negative affectivity (neuroticism) is a well-established risk factor for the onset 
of major depressive disorder, and high levels appear to render individuals more likely to develop 
depressive episodes in response to stressful life events. 


Environmental. 
Adverse childhood experiences, particularly when they are multiple and of 
diverse types, constitute a set 
of potent 
risk factors for major depressive disorder. Women may 
be disproportionately at 
risk for adverse childhood experiences, including sexual 
abuse, that 
may 
contribute to the increased prevalence of depression in this group. Other social 
determinants of 
mental 
health, such as low income, limited formal 
education, racism, and other forms of 
discrimination, are associated with higher risk of major depressive disorder. Stressful 
life events 
are well 
recognized as precipitants of major depressive episodes, but 
the presence or absence of 
adverse life events near the onset 
of episodes does not 
appear to provide a useful 
guide to 
prognosis or treatment 
selection. Etiologically, women are disproportionately affected by major 
risk factors for depression across the life span, including interpersonal trauma. 


Genetic 
and 
physiological. 
First-degree family members of individuals with major depressive 
disorder have a risk for major depressive disorder two- to fourfold higher than that 
of the general 
population. Relative risks appear to be higher for early-onset 
and recurrent 
forms. Heritability is 
approximately 40%, and the personality trait 
neuroticism 
accounts for a substantial 
portion of 
this genetic liability. 


Women may also be at 
risk for depressive disorders in relation to specific reproductive life 
stages, including in the premenstrual period, postpartum, and in perimenopause. 
Course 
modifiers. 
Essentially all 
major nonmood disorders (i.e., anxiety, substance use, trauma-
and stressor-related, feeding and eating, and obsessive-compulsive and related disorders) 
increase the risk of an individual 
developing depression. Major depressive episodes that 
develop 
against 
the background of another disorder often follow a more refractory course. Substance use, 
anxiety, and borderline personality disorders are among the most 
common of these, and the 
presenting depressive symptoms may obscure and delay their recognition. However, sustained 



clinical 
improvement 
in depressive symptoms may depend on the appropriate treatment 
of 
underlying illnesses. Chronic or disabling medical 
conditions also increase risks for major 
depressive episodes. Prevalent 
illnesses such as diabetes, morbid obesity, and cardiovascular 
disease are often complicated by depressive episodes, and these episodes are more likely to 
become chronic than are depressive episodes in medically healthy individuals. 


Culture-Related Diagnostic Issues 


Although there is substantial 
cross-cultural 
variation in the prevalence, course, and 
symptomatology of depression, a syndrome similar to major depressive disorder can be 
identified across diverse cultural 
contexts. Symptoms commonly associated with depression 
across cultural 
contexts, not 
listed in the DSM criteria, include social 
isolation or loneliness, 
anger, crying, and diffuse pain. A wide range of other somatic complaints are 


190 


common and vary by cultural 
context. Understanding the significance of these symptoms 
requires exploring their meaning in local social contexts. 


Symptoms of major depressive disorder may be underdetected or underreported, potentially 
leading to misdiagnosis, including overdiagnosis of schizophrenia spectrum 
disorders in some 
ethnic and racialized groups facing discrimination. Cross-nationally, higher levels of income 
inequality in a society are associated with higher prevalence of major depressive disorder. In the 
United States, the chronicity of major depressive disorder appears to be higher among African 
Americans and Caribbean Blacks compared with non-Latinx Whites, possibly because of the 
impact 
of racism, discrimination, greater sociostructural 
adversity, and lack of access to quality 
mental health care. 


Sex- and Gender-Related Diagnostic Issues 


There are no clear differences between genders in treatment 
response or functional 
consequences. There is some evidence for sex and gender differences in phenomenology and 
course of illness. Women tend to experience more disturbances in appetite and sleep, including 
atypical 
features such as hyperphagia and hypersomnia, and are more likely to experience 
interpersonal 
sensitivity and gastrointestinal 
symptoms. Men with depression, however, may be 
more likely than depressed women to report 
greater frequencies and intensities of maladaptive 
self-coping and problem-solving strategies, including alcohol 
or other drug misuse, risk taking, 
and poor impulse control. 


Association With Suicidal 
Thoughts or Behavior 


Age-adjusted rates of suicide in the United States have increased from 
10.5 to 14.0 per 100,000 
over the past 
two decades. An earlier review of the literature indicated that 
individuals with 
depressive illness have a 17-fold increased risk for suicide over the age- and sex-adjusted general 
population rate. The likelihood of suicide attempts lessens in middle and late life, although the 
risk of death by suicide does not. The possibility of suicidal 
behavior exists at 
all 
times during 
major depressive episodes. The most 
consistently described risk factor is a past 
history of suicide 
attempts or threats, but 
it 
should be remembered that 
most 
deaths by suicide are not 
preceded by 



nonfatal 
attempts. Anhedonia has a particularly strong association with suicidal 
ideation. Other 
features associated with an increased risk for death by suicide include being single, living alone, 
social 
disconnectedness, early life adversity, availability of lethal 
methods such as a firearm, 
sleep disturbance, cognitive and decision-making deficits, and having prominent 
feelings of 
hopelessness. Women attempt 
suicide at 
a higher rate than men, while men are more likely to 
complete suicide. The difference in suicide rate between men and women with depressive 
disorders is smaller than in the population as a whole, however. Comorbidities, including 
aggressive-impulsive traits, borderline personality disorder, substance use disorder, anxiety, 
other medical conditions, and functional impairment, increase risk for future suicidal behavior. 


Functional 
Consequences of Major Depressive Disorder 


Many of the functional 
consequences of major depressive disorder derive from 
individual 
symptoms. Impairment 
can be very mild, such that 
many of those who interact 
with the affected 
individual 
are unaware of depressive symptoms. Impairment 
may, however, range to complete 
incapacity such that 
the depressed individual 
is unable to attend to basic self-care needs or is 
mute or catatonic. For individuals seen in general 
medical 
settings, those with major depressive 
disorder have more pain and physical 
illness and greater decreases in physical, social, and role 
functioning. Depressed women report 
greater functional 
impairment 
in their relationships than 
men. 


191 


Differential 
Diagnosis 


Manic 
episodes 
with 
irritable 
mood 
or with 
mixed 
features. 
Major depressive episodes with prominent 
irritable mood may be difficult 
to distinguish from 
manic episodes with irritable mood or with 
mixed features. This distinction requires a careful 
clinical 
evaluation of the presence of sufficient 
manic symptoms to meet 
threshold criteria (i.e., three if mood is manic, four if mood is irritable 


but not manic). 
Bipolar I 
disorder, 
bipolar II 
disorder, 
or other specified 
bipolar and 
related 
disorder. 
Major depressive 
episodes along with a history of 
a manic or hypomanic episode preclude the diagnosis of major 


depressive disorder. Major depressive episodes with a history of hypomanic episodes and 
without 
a history of manic episodes indicate a diagnosis of bipolar II disorder, whereas major 
depressive episodes with a history of manic episodes (with or without 
hypomanic episodes) 
indicate a diagnosis of bipolar I disorder. On the other hand, presentations of major depressive 
episodes with a history of periods of hypomania that 
do not 
meet 
criteria for a hypomanic 
episode may be diagnosed as either other specified bipolar and related disorder or major 
depressive disorder depending on where the clinician judges the presentation to best 
fall. For 
example, the presentation may be best 
considered other specified bipolar and related disorder 
because of the clinical 
significance of the subthreshold hypomanic symptoms, or the presentation 
may be best 
considered a case of major depressive disorder with some subthreshold hypomanic 
symptoms in between episodes. 
Depressive 
disorder due 
to 
another medical 
condition. 
A diagnosis of depressive disorder due to 


another medical 
condition requires the presence of an etiological 
medical 
condition. Major 



depressive disorder is not 
diagnosed if the major depressive like episodes are all 
attributable to 
the direct 
pathophysiological 
consequence of a specific medical 
condition (e.g., multiple 
sclerosis, stroke, hypothyroidism). 
Substance/medication-induced 
depressive 
disorder. 
This disorder is distinguished from 
major 


depressive disorder by the fact 
that 
a substance (e.g., a drug of abuse, a medication, a toxin) 
appears to be etiologically related to the mood disturbance. For example, depressed mood that 
occurs only in the context 
of withdrawal 
from 
cocaine would be diagnosed as cocaine-induced 
depressive disorder. 


Persistent 
depressive 
disorder. 
Persistent 
depressive disorder is characterized by depressed mood, 
more days than not, for at 
least 
2 years. If criteria are met 
for both major depressive disorder and 
persistent depressive disorder, both can be diagnosed. 


Premenstrual 
dysphoric 
disorder. 
Premenstrual 
dysphoric disorder is characterized by dysphoric 
mood that 
is present 
in the final 
week before the onset 
of menses, that 
starts to improve within a 
few days after the onset 
of menses, and that 
becomes minimal 
or absent 
in the week postmenses. 
By contrast, the episodes of major depressive disorder are not 
temporally connected to the 
menstrual cycle. 


Disruptive 
mood 
dysregulation 
disorder. 
Disruptive mood dysregulation disorder is characterized by 
severe, recurrent 
temper outbursts manifested verbally and/or behaviorally, accompanied by 
persistent 
or labile mood, most 
of the day, nearly every day, in between the outbursts. In 
contrast, in major depressive disorder, irritability is confined to the major depressive episodes. 


Major depressive 
episodes 
superimposed 
on 
schizophrenia, 
delusional 
disorder, 
schizophreniform disorder, 
or other specified 
or unspecified 
schizophrenia 
spectrum and 
other 
psychotic 
disorder.

Depressive symptoms may be present 
during schizophrenia, delusional 
disorder, 
schizophreniform 
disorder, or other specified or unspecified schizophrenia spectrum 
and other 
psychotic disorder. Most 
commonly, such depressive symptoms can be considered associated 
features of these disorders and do not merit a 


192 


separate diagnosis. However, when the depressive symptoms 
meet 
full 
criteria for a major 
depressive episode, a diagnosis of other specified depressive disorder may be made in addition to 
the diagnosis of the psychotic disorder. 


Schizoaffective 
disorder. 
Schizoaffective disorder differs from 
major depressive disorder, with 
psychotic features, by the requirement 
that 
in schizoaffective disorder, delusions or 
hallucinations are present for at least 2 weeks in the absence of a major depressive episode. 


Attention-deficit/hyperactivity 
disorder. 
Distractibility and low frustration tolerance can occur in 
both attention-deficit/hyperactivity disorder (ADHD) and a major depressive episode; 
if the 
criteria are met 
for both, ADHD may be diagnosed in addition to the mood disorder. However, 
the clinician must 
be cautious not 
to overdiagnose a major depressive episode in children with 
ADHD whose disturbance in mood is characterized by irritability rather than by sadness or loss 
of interest. 


Adjustment 
disorder with 
depressed 
mood. 
A major depressive episode that 
occurs in response to a 
psychosocial 
stressor is distinguished from 
adjustment 
disorder, with depressed mood, by the 



fact that the full criteria for a major depressive episode are not met in adjustment disorder. 
Bereavement. 
Bereavement 
is the experience of losing a loved one to death. It 
generally triggers 
a grief response that 
may be intense and may involve many features that 
overlap with symptoms 
characteristic of a major depressive episode, such as sadness, difficulty sleeping, and poor 
concentration. Features that 
help differentiate a bereavement-related grief response from 
a major 
depressive episode include the following: 
the predominant 
affects in grief are feelings of 
emptiness and loss, whereas in a major depressive episode they are persistent 
depressed mood 
and a diminished ability to experience pleasure. Moreover, the dysphoric mood of grief is likely 
to decrease in intensity over days to weeks and occurs in waves that 
tend to be associated with 
thoughts or reminders of the deceased, whereas the depressed mood in a major depressive 
episode is more persistent 
and not 
tied to specific thoughts or preoccupations. It 
is important 
to 
note that 
in a vulnerable individual 
(e.g., someone with a past 
history of major depressive 


disorder), bereavement 
may trigger not 
only a grief response but 
also the development 
of an 
episode of depression or the worsening of an existing episode. 
Sadness. 
Finally, periods of sadness are inherent 
aspects of the human experience. These 


periods should not 
be diagnosed as a major depressive episode unless criteria are met 
for severity 
(i.e., five out 
of nine symptoms), duration (i.e., most 
of the day, nearly every day for at 
least 
2 
weeks), and clinically significant 
distress or impairment. The diagnosis other specified 
depressive disorder may be appropriate for presentations of depressed mood with clinically 
significant impairment that do not meet criteria for duration or severity. 


Comorbidity 


Other disorders with which major depressive disorder frequently co-occurs are substance-related 
disorders, panic disorder, generalized anxiety disorder, posttraumatic stress disorder, obsessive-
compulsive disorder, anorexia nervosa, bulimia nervosa, and borderline personality disorder. 


While women are more likely than men to report 
comorbid anxiety disorders, bulimia 
nervosa, and somatoform 
disorder (somatic symptom 
and related disorders), men are more likely 
to report comorbid alcohol and substance abuse. 


193 


Persistent Depressive Disorder 


Diagnostic Criteria 
F34.1 


This disorder represents a 
consolidation 
of 
DSM-IV-defined 
chronic major 
depressive 
disorder and 
dysthymic disorder. 


A. 
Depressed 
mood 
for most 
of 
the 
day, 
for more 
days than 
not, 
as indicated 
by 
either subjective 
account 
or observation 
by others, 
for at 
least 
2 
years. 
Note: 
In 
children 
and 
adolescents, 
mood 
can 
be 
irritable 
and 
duration 
must 
be 
at 
least 
1 
year. 


B. 
Presence, 
while 
depressed, 
of 
two 
(or more) of 
the 
following: 

1. 
Poor appetite 
or overeating. 
2. 
Insomnia 
or hypersomnia. 
3. 
Low energy or fatigue. 
4. 
Low self-esteem. 
5. 
Poor concentration 
or difficulty making 
decisions. 
6. 
Feelings of 
hopelessness. 
C. 
During 
the 
2-year period 
(1 
year for children 
or adolescents) of 
the 
disturbance, 
the 
individual has never been 
without 
the 
symptoms in 
Criteria 
A 
and 
B 
for more 
than 
2 
months at 
a 
time. 
D. 
Criteria 
for a 
major depressive 
disorder may be 
continuously present 
for 2 
years. 
E. 
There 
has never been 
a 
manic episode 
or a 
hypomanic episode. 
F. 
The 
disturbance 
is not 
better explained 
by a 
persistent 
schizoaffective 
disorder, 
schizophrenia, 
delusional disorder, 
or other specified 
or unspecified 
schizophrenia 
spectrum and 
other psychotic disorder. 
G. 
The 
symptoms are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition 
(e.g., 
hypothyroidism). 
H. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Note: 
If 
criteria 
are 
sufficient 
for a 
diagnosis of 
a 
major depressive 
episode 
at 
any 
time 
during 
the 
2-year period 
of 
depressed 
mood, 
then 
a 
separate 
diagnosis of 
major 
depression 
should 
be 
made 
in 
addition 
to 
the 
diagnosis of 
persistent 
depressive 
disorder along 
with 
the 
relevant 
specifier (e.g., 
with 
intermittent 
major depressive 
episodes, 
with 
current 
episode). 


Specify 
if: 
With 
anxious 
distress 
(pp. 
210 211) 
With 
atypical 
features 
(p. 
212) 


Specify 
if: 
In 
partial 
remission 
(p. 
214) 
In 
full 
remission 
(p. 
214) 


Specify 
if: 
Early 
onset: 
If 
onset 
is before 
age 
21 
years. 
Late 
onset: 
If 
onset 
is at 
age 
21 
years or older. 


Specify 
if 
(for most 
recent 
2 
years of 
persistent 
depressive 
disorder): 


With 
pure 
dysthymic 
syndrome: 
Full criteria 
for a 
major depressive 
episode 
have 
not 
been 
met 
in 
at 
least 
the 
preceding 
2 
years. 
With 
persistent major depressive 
episode: 
Full criteria 
for 
a 
major depressive 


episode 
have 
been 
met 
throughout 
the 
preceding 
2-year period. 


194 



With 
intermittent major depressive 
episodes, 
with 
current episode: 
Full 
criteria 
for a 
major depressive 
episode 
are 
currently met, 
but 
there 
have 
been 
periods of 
at 
least 
8 
weeks in 
at 
least 
the 
preceding 
2 
years with 
symptoms 
below the 
threshold 
for a 
full major depressive 
episode. 


With 
intermittent major depressive 
episodes, 
without current episode: 
Full 
criteria 
for a 
major depressive 
episode 
are 
not 
currently met, 
but 
there 
has been 
one 
or more 
major depressive 
episodes in 
at 
least 
the 
preceding 
2 
years. 


Specify 
current 
severity: 
Mild 
(p. 
214) 
Moderate 
(p. 
214) 
Severe 
(p. 
214) 


Diagnostic Features 


The essential 
feature of persistent 
depressive disorder is a depressed mood that 
occurs for most 
of the day, for more days than not, for at 
least 
2 years, or at 
least 
1 year for children and 
adolescents (Criterion A). This disorder represents a consolidation of DSM-IV-defined chronic 
major depressive disorder and dysthymic disorder. Major depression may precede persistent 
depressive disorder, and major depressive episodes may occur during persistent 
depressive 
disorder. Individuals whose symptoms meet 
major depressive disorder criteria for 2 years should 
be given a diagnosis of persistent depressive disorder as well as major depressive disorder. 


Individuals with persistent 
depressive disorder describe their mood as sad or  down in the 
dumps.  During periods of depressed mood, at 
least 
two of the six symptoms from 
Criterion B 
are present. Because these symptoms have become a part 
of the individual s day-to-day 
experience, particularly in the case of early onset 
(e.g.,  I ve always been this way ), they may 
not 
be reported unless the individual 
is directly prompted. During the 2-year period (1 year for 
children or adolescents), any symptom-free intervals that 
have occurred have lasted no longer 
than 2 months (Criterion C). 


Prevalence 


Persistent 
depressive disorder is effectively an amalgam 
of DSM-IV dysthymic disorder and 
chronic major depressive episode. The 12-month prevalence in the United States is 
approximately 0.5% for dysthymic disorder and 1.5% for chronic major depressive disorder, 
with prevalence among women approximately 1.5 and 2 times higher than prevalence among 
men for each of these diagnoses, respectively. Based on studies using comparable ascertainment 
procedures, the lifetime and 12-month estimates of DSM-IV dysthymia may be higher in high-
income than in low- and middle-income countries. However, the disorder is associated with 
elevated risk of suicidal outcomes and comparable levels of disability wherever it occurs. 


Development and Course 


Persistent 
depressive disorder often has an early and insidious onset 
(i.e., in childhood, 
adolescence, or early adult 
life) and, by definition, a chronic course. Borderline personality 
disorder is a particularly robust 
risk factor for persistent 
depressive disorder. When persistent 



depressive disorder and borderline personality disorder coexist, the covariance of the 
corresponding features over time suggests the operation of a common mechanism. Early onset 
(i.e., before age 21 years) is associated with a higher likelihood of comorbid personality 
disorders and substance use disorders. 


When symptoms rise to the level 
of a major depressive episode, they are likely to 
subsequently revert 
to a lower level. However, depressive symptoms are much less likely to 
resolve fully in a given period of time in the context 
of persistent 
depressive disorder than they 
are in a nonchronic major depressive episode. 


195 


Risk and Prognostic Factors 


Temperamental. 
Factors predictive of poorer long-term 
outcome include higher levels of negative 
affectivity (neuroticism), greater symptom 
severity, poorer global 
functioning, and presence of 
anxiety disorders or conduct disorder. 


Environmental. 
Childhood risk factors include parental 
loss or separation and childhood 


adversity. 
Genetic 
and 
physiological. 
There are no clear differences in illness development, course, or family 
history between DSM-IV dysthymic disorder and chronic major depressive disorder. Earlier 
findings pertaining to either disorder are therefore likely to apply to persistent 
depressive 
disorder. It 
is thus likely that 
individuals with persistent 
depressive disorder will 
have a higher 
proportion of first-degree relatives with persistent 
depressive disorder than do individuals with 
nonchronic major depressive disorder, and more depressive disorders in general. 


A number of brain regions (e.g., prefrontal 
cortex, anterior cingulate, amygdala, 
hippocampus) have been implicated in persistent 
depressive disorder. Possible 
polysomnographic abnormalities exist as well. 


Culture-Related Diagnostic Issues 


The perceived abnormality or tolerance of chronic depressive symptoms may vary across 
cultures, affecting symptom 
detection and treatment 
acceptability. For example, some social 
groups or age cohorts may consider long-standing depressive symptoms to be normal 
reactions 
to adversity. 


Association With Suicidal 
Thoughts or Behavior 


Persistent 
depressive disorder is associated with elevated risk of suicidal 
outcomes and 
comparable levels of disability, whether the disorder occurs in high-, middle-, or low-income 
countries. 


Functional 
Consequences of Persistent Depressive Disorder 


The degree to which persistent 
depressive disorder impacts social 
and occupational 
functioning 
is likely to vary widely, but 
effects can be as great 
as or greater than those of major depressive 
disorder. 



Differential 
Diagnosis 


Major depressive 
disorder. 
If there is a depressed mood for more days than not 
plus two or more 
persistent 
depressive disorder Criterion B 
symptoms for 2 years or more, then the diagnosis of 
persistent 
depressive disorder is made. If the symptom 
criteria are sufficient 
for a diagnosis of a 
major depressive episode at 
any time during this period, then the additional 
diagnosis of major 
depression should be made. The comorbid presence of major depressive episodes during this 
period should also be noted by assigning the appropriate course specifier to the persistent 
depressive disorder diagnosis as follows: 
If the individual s symptoms currently meet 
full 
criteria 
for a major depressive episode, and there have been periods of at 
least 
8 weeks in at 
least 
the 
preceding 2 years with symptoms below the threshold for a full 
major depressive episode, then 
the specifier  with intermittent 
major depressive episodes, with current 
episode  would be 
assigned. If full 
criteria for a major depressive episode are not 
currently met 
but 
there has been 
one or more major depressive episodes in at 
least 
the preceding 2 years, then the specifier  with 
intermittent 
major depressive episodes, without 
current 
episode  is assigned. If a major 
depressive episode 


196 


has persisted for at 
least 
a 2-year duration and remains present, then the specifier  with persistent 
major depressive episode  is used. If the individual 
has not 
experienced an episode of major 
depression in the last 2 years, then the specifier  with pure dysthymic syndrome  is used. 


Other specified 
depressive 
disorder. 
Because the criteria for a major depressive episode include 
symptoms (i.e., markedly diminished interest 
or pleasure in activities; 
psychomotor agitation or 
retardation; 
recurrent 
thoughts of death, suicidal 
ideation, suicide attempt 
or plan) that 
are absent 
from 
the symptom 
list 
for persistent 
depressive disorder (i.e., depressed mood and two out 
of six 
Criterion B 
symptoms), a very limited number of individuals will 
have depressive symptoms that 
have persisted longer than 2 years but 
that 
do not 
meet 
criteria for persistent 
depressive disorder. 
If full 
criteria for a major depressive episode have been met 
at 
some point 
during the current 
episode of illness, a diagnosis of major depressive disorder would apply. Otherwise, a diagnosis 
of other specified depressive disorder or unspecified depressive disorder should be given. 


Bipolar I 
and 
bipolar II 
disorders. 
A history of a manic or hypomanic episode precludes the 
diagnosis of persistent 
depressive disorder. A history of manic episodes (with or without 
hypomanic episodes) indicates a diagnosis of bipolar I disorder. A history of hypomanic episodes 
(without 
any history of manic episodes in individuals with persistent 
depressive presentations 
during which criteria have been met 
for a major depressive episode) warrants a diagnosis of 
bipolar II disorder. Other specified bipolar disorder applies to individuals whose presentations 
include a history of hypomanic episodes along with persistent 
depressive presentation that 
has 
never met full criteria for a major depressive episode. 


Cyclothymic 
disorder. 
A diagnosis of cyclothymic disorder precludes the diagnosis of persistent 
depressive disorder. Thus, if during the period lasting at least 2 years of depressed mood for most 
of the day, for more days than not, 1) there are numerous periods with hypomanic symptoms that 
do not 
meet 
criteria for a hypomanic episode, 2) there have not 
been any symptom-free periods 
of more than 2 months at 
a time, and 3) criteria have never been met 
for a major depressive, 
manic, or hypomanic episode, then the diag-nosis would be cyclothymic disorder instead of 



persistent depressive disorder. 
Psychotic 
disorders. 
Depressive symptoms are a common associated feature of chronic psychotic 
disorders (e.g., schizoaffective disorder, schizophrenia, delusional 
disorder). A separate 
diagnosis of persistent 
depressive disorder is not 
made if the symptoms occur only during the 


course of the psychotic disorder (including residual phases). 
Depressive 
or bipolar and 
related 
disorder due 
to 
another medical 
condition. 
Persistent 
depressive 
disorder must 
be distinguished from 
a depressive or bipolar and related disorder due to another 


medical 
condition. The diagnosis is depressive or bipolar and related disorder due to another 
medical 
condition if the mood disturbance is judged, based on history, physical 
examination, or 
laboratory findings, to be attributable to the direct 
pathophysiological 
effects of a specific, 
usually chronic, medical 
condition (e.g., multiple sclerosis). If it 
is judged that 
the depressive 
symptoms are not 
attributable to the physiological 
effects of another medical 
condition, then the 
primary mental 
disorder (e.g., persistent 
depressive disorder) is recorded, and the medical 
condition is noted as a concomitant medical condition (e.g., diabetes mellitus). 
Substance/medication-induced 
depressive 
or bipolar and 
related 
disorder. 
A substance/medication


induced depressive or bipolar and related disorder is distinguished from 
persistent 
depressive 
disorder when a substance (e.g., a drug of abuse, a medication, a toxin) is judged to be 
etiologically related to the mood disturbance. 


Personality 
disorders. 
A personality disorder is characterized by an enduring pattern of inner 
experience and behavior that deviates markedly from the expectations of the 


197 


individual s culture, with onset 
by adolescence or early adulthood. Personality disorders 
commonly co-occur with persistent 
depressive disorder. If criteria are met 
for persistent 
depressive disorder and a personality disorder, both may be diagnosed. 


Comorbidity 


In comparison to individuals with major depressive disorder, those with persistent 
depressive 
disorder are at 
higher risk for psychiatric comorbidity in general, and for anxiety disorders, 
substance use disorders, and personality disorders in particular. Early-onset 
persistent 
depressive 
disorder is strongly associated with DSM-5 Cluster B and C personality disorders. 


Premenstrual 
Dysphoric Disorder 


Diagnostic Criteria 
F32.81 


A. 
In 
the 
majority of 
menstrual cycles, 
at 
least 
five 
symptoms must 
be 
present 
in 
the 
final week before 
the 
onset 
of 
menses, 
start 
to 
improve 
within 
a 
few days after 
the 
onset 
of 
menses, 
and 
become 
minimal 
or absent 
in 
the 
week postmenses. 
B. 
One 
(or more) of 
the 
following 
symptoms must 
be 
present: 

1. 
Marked 
affective 
lability (e.g., 
mood 
swings; 
feeling 
suddenly sad 
or tearful, 
or 
increased 
sensitivity to 
rejection). 
2. 
Marked 
irritability or anger or increased 
interpersonal conflicts. 
3. 
Marked 
depressed 
mood, 
feelings of 
hopelessness, 
or self-deprecating 
thoughts. 
4. 
Marked 
anxiety, 
tension, 
and/or feelings of 
being 
keyed 
up 
or on 
edge. 
C. 
One 
(or more) of 
the 
following 
symptoms must 
additionally be 
present, 
to 
reach 
a 
total of 
five 
symptoms when 
combined 
with 
symptoms from Criterion 
B 
above. 
1. 
Decreased 
interest 
in 
usual activities (e.g., 
work, 
school, 
friends, 
hobbies). 
2. 
Subjective 
difficulty in 
concentration. 
3. 
Lethargy, 
easy fatigability, 
or marked 
lack of 
energy. 
4. 
Marked 
change 
in 
appetite; 
overeating; 
or specific food 
cravings. 
5. 
Hypersomnia 
or insomnia. 
6. 
A 
sense 
of 
being 
overwhelmed 
or out 
of 
control. 
7. 
Physical symptoms such 
as breast 
tenderness or swelling, 
joint 
or muscle 
pain, 
a 
sensation 
of 
 bloating,  or weight 
gain. 
Note: 
The 
symptoms in 
Criteria 
A C must 
have 
been 
met 
for most 
menstrual 
cycles that 
occurred 
in 
the 
preceding 
year. 


D. 
The 
symptoms cause 
clinically significant 
distress or interference 
with 
work, 
school, 
usual social activities, 
or relationships with 
others (e.g., 
avoidance 
of 
social activities; 
decreased 
productivity and 
efficiency at 
work, 
school, 
or home). 
E. 
The 
disturbance 
is not 
merely an 
exacerbation 
of 
the 
symptoms of 
another 
disorder, 
such 
as major depressive 
disorder, 
panic disorder, 
persistent 
depressive 
disorder, 
or a 
personality disorder (although 
it 
may co-occur with 
any 
of 
these 
disorders). 
F. 
Criterion 
A 
should 
be 
confirmed 
by prospective 
daily ratings during 
at 
least 
two 
symptomatic cycles. 
(Note: 
The 
diagnosis may be 
made 
provisionally prior to 
this confirmation.) 
G. 
The 
symptoms are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication, 
other treatment) or another medical 
condition 
(e.g., 
hyperthyroidism). 
198 


Recording Procedures 


If symptoms have not 
been confirmed by prospective daily ratings of at 
least 
two symptomatic 
cycles,  provisional  should be noted after the name of the diagnosis (i.e.,  premenstrual 
dysphoric disorder, provisional ). 


Diagnostic Features 



The essential 
features of premenstrual 
dysphoric disorder are the expression of mood lability, 
irritability, dysphoria, and anxiety symptoms that 
occur repeatedly during the premenstrual 
phase 
of the cycle and remit 
around the onset 
of menses or shortly thereafter. These symptoms may be 
accompanied by behavioral 
and physical 
symptoms. Symptoms must 
have occurred in most 
of 
the menstrual 
cycles during the past 
year and must 
have an adverse effect 
on work or social 
functioning. The intensity and/or expressivity of the accompanying symptoms may be closely 
related to social 
and cultural 
background characteristics as well 
as religious beliefs, social 
tolerance, attitude toward the female reproductive cycle, and female gender role issues more 
generally. 


Typically, symptoms peak around the time of the onset 
of menses. Although it 
is not 
uncommon for symptoms to linger into the first 
few days of menses, the individual 
must 
have a 
symptom-free period in the follicular phase after the menstrual 
period begins. While the core 
symptoms include mood and anxiety symptoms, behavioral 
and somatic symptoms commonly 
also occur. However, the presence of somatic and/or behavioral 
symptoms in the absence of 
mood and/or anxious symptoms is not 
sufficient 
for a diagnosis. Symptoms are of comparable 
severity (but 
not 
duration) to those of other mental 
disorders, such as a major depressive episode 
or generalized anxiety disorder. In order to confirm 
a provisional 
diagnosis, daily prospective 
symptom ratings are required for at least two symptomatic cycles. 


Symptoms must 
cause clinically significant 
distress and/or an obvious and marked 
impairment in the ability to function socially or occupationally in the week prior to menses. 


Associated Features 


Delusions and hallucinations have been described in the late luteal 
phase of the menstrual 
cycle 
but are rare. 


Prevalence 


The 12-month prevalence of premenstrual 
dysphoric disorder in the community has been 
estimated at 
5.8% based on a large study from 
Germany. Another study that 
looked at 
prevalence 
over two menstrual 
cycles found 1.3% of menstruating women with the disorder in the United 
States. Estimates based on retrospective reports are often higher than those based on prospective 
daily ratings. Yet, estimates based on a daily record of symptoms for 1 2 months may not 
be 
fully representative, because those with the most 
severe symptoms may be unable to sustain the 
rating process. The most 
rigorous estimate of premenstrual 
dysphoric disorder prevalence in the 
United States using prospective ratings of two consecutive menstrual 
cycles was 1.3% for 
women whose symptoms met 
diagnostic criteria, who experienced functional 
impairment, and 
had no co-occurring mental 
disorder. The prevalence of premenstrual 
dysphoric disorder 
symptoms in adolescent girls may be higher than that observed in adult women. 


Development and Course 


Onset 
of premenstrual 
dysphoric disorder can occur at 
any point 
after menarche. Incidence of 
new cases over a 40-month follow-up period in Germany is 2.5% (95% confidence interval 
= 
1.7 3.7). Symptoms cease after menopause, although cyclical 
hormone replacement 
can trigger 
the re-expression of symptoms. 



199 


Risk and Prognostic Factors 


Environmental. 
Environmental 
factors associated with the expression of premenstrual 
dysphoric 
disorder include stress, history of interpersonal 
trauma, seasonal 
changes, and sociocultural 
aspects of female sexual behavior in general, and female gender roles in particular. 


Genetic 
and 
physiological. 
No studies have examined heritability in premenstrual 
dysphoric 
disorder specifically. Estimates for heritability of premenstrual 
dysphoric symptoms range 
between 30% and 80%, although it 
remains unclear whether the symptoms themselves are 
heritable or whether they are simply associated with other heritable factors or traits. 


Culture-Related Diagnostic Issues 


Premenstrual 
dysphoric disorder has been observed in individuals in the United States, Europe, 
India, Nigeria, Brazil, and Asia, with a broad prevalence range. Nevertheless, as with most 
mental 
disorders, frequency, intensity, and expressivity of symptoms; 
perceived consequences; 
help-seeking patterns; 
and management 
may be significantly influenced by social 
and cultural 
factors, such as a history of sexual 
abuse or domestic violence, limited social 
support, and 
cultural variations in attitudes toward menstruation. 


Diagnostic Markers 


As indicated earlier, the diagnosis of premenstrual 
dysphoric disorder is appropriately confirmed 
by 2 months of prospective symptom 
ratings. A number of scales, including the Daily Rating of 
Severity of Problems and the Visual 
Analogue Scales for Premenstrual 
Mood Symptoms, have 
undergone validation and are commonly used in clinical 
trials for premenstrual 
dysphoric 
disorder. The Premenstrual 
Tension Syndrome Rating Scale has a self-report 
and an observer 
version, both of which have been validated and used widely to measure illness severity in women 
who have premenstrual dysphoric disorder. 


Association With Suicidal 
Thoughts or Behavior 


The premenstrual phase has been considered by some to be a risk period for suicide. 


Functional 
Consequences of Premenstrual 
Dysphoric Disorder 


Impairment 
in social 
functioning may be manifested by discord in the intimate partner 
relationship and problems with children, other family members, or friends that 
occur only in 
association with the premenstrual 
dysphoric disorder (i.e., as opposed to chronic interpersonal 
problems). Impairments in work and health-related quality of life are also prominent. There is 
evidence that 
premenstrual 
dysphoric disorder can be associated with impairments in function 
and health-related quality of life that 
are on par with those observed in major depressive disorder 
and persistent depressive disorder. 


Differential 
Diagnosis 


Premenstrual 
syndrome. 
Premenstrual 
syndrome differs from 
premenstrual 
dysphoric disorder in 



that 
premenstrual 
syndrome does not 
require a minimum 
of five symptoms nor mood-related 
symptomatology, and it 
is generally considered to be less severe than premenstrual 
dysphoric 
disorder. Premenstrual 
syndrome may be more common than premenstrual 
dysphoric disorder; 
its estimated prevalence varies with numbers that 
hover at 
about 
20%. While premenstrual 
syndrome shares the feature of symptom 
expression during the premenstrual 
phase of the 
menstrual cycle, the presence of somatic or 


200 


behavioral 
symptoms, without 
the required affective symptoms, likely meets criteria for 


premenstrual syndrome and not for premenstrual dysphoric disorder. 
Dysmenorrhea. 
Dysmenorrhea is a syndrome of painful 
menses, but 
this is 
distinct 
from 
a 
syndrome characterized by affective changes. Moreover, symptoms of dysmenorrhea begin with 
the onset 
of menses, whereas symptoms of premenstrual 
dysphoric disorder, by definition, begin 
before the onset of menses, even if they linger into the first few days of menses. 
Bipolar disorder, 
major depressive 
disorder, 
and 
persistent 
depressive 
disorder. 
Many women with 


(either naturally occurring or substance/medication-induced) bipolar or major depressive disorder 
or persistent 
depressive disorder believe that 
they have premenstrual 
dysphoric disorder. 
However, when they chart 
symptoms, they realize that 
the symptoms do not 
follow a 
premenstrual 
pattern. Because the onset 
of menses constitutes a memorable event, they may 
report 
that 
symptoms occur only during the premenstruum 
or that 
symptoms worsen 
premenstrually. This is one of the rationales for the requirement 
that 
symptoms be confirmed by 
daily prospective ratings. The process of differential 
diagnosis, particularly if the clinician relies 
on retrospective symptoms only, is made more difficult 
because of the overlap between 
symptoms of premenstrual 
dysphoric disorder and some other diagnoses. The overlap of 
symptoms is particularly salient 
for differentiating premenstrual 
dysphoric disorder from 
major 
depressive episodes, persistent 
depressive disorder, bipolar disorders, and borderline personality 
disorder. 


Use 
of 
hormonal 
treatments. 
Some women who present 
with moderate to severe premenstrual 
symptoms may be using hormonal 
treatments, including hormonal 
contraceptives. If such 
symptoms occur after initiation of exogenous hormone use, the symptoms may be attributable to 
the use of hormones rather than to the underlying condition of premenstrual 
dysphoric disorder. 
If the woman stops hormones and the symptoms disappear, then this is consistent 
with 
substance/medication-induced depressive disorder. 


Other medical 
conditions. 
Women with chronic medical 
conditions may experience symptoms of 
premenstrual 
dysphoria. As with any depressive disorder, medical 
conditions that 
could better 
account for the symptoms should be ruled out, such as thyroid deficiency and anemia. 


Comorbidity 


A major depressive episode is the most 
frequently reported previous disorder in individuals 
presenting with premenstrual 
dysphoric disorder. A wide range of medical 
conditions (e.g., 
migraine, asthma, allergies, seizure disorders) or other mental 
disorders (e.g., depressive and 
bipolar disorders, anxiety disorders, bulimia nervosa, substance use disorders) may worsen in the 



premenstrual 
phase; 
however, the absence of a symptom-free period during the postmenstrual 
interval 
obviates a diagnosis of premenstrual 
dysphoric disorder. These conditions are better 
considered premenstrual 
exacerbation of a current 
mental 
disorder or medical 
condition. 
Although the diagnosis of premenstrual 
dysphoric disorder should not 
be assigned in situations 
in which an individual 
experiences only a premenstrual 
exacerbation of another mental 
or 
physical 
disorder, it 
can be considered in addition to the diagnosis of another mental 
disorder or 
medical 
condition if the individual 
experiences symptoms and changes in level 
of functioning 
that 
are characteristic of premenstrual 
dysphoric disorder and markedly different 
from 
the 
symptoms experienced as part of the ongoing disorder. 


201 


Substance/Medication-Induced 
Depressive Disorder 


Diagnostic Criteria 


A. 
A 
prominent 
and 
persistent 
disturbance 
in 
mood 
that 
predominates in 
the 
clinical 
picture 
and 
is characterized 
by depressed 
mood 
or markedly diminished 
interest 
or pleasure 
in 
all, 
or almost 
all, 
activities. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
of 
both 
(1) and 
(2): 
1. 
The 
symptoms in 
Criterion 
A 
developed 
during 
or soon 
after substance 
intoxication 
or withdrawal or after exposure 
to 
or withdrawal from a 
medication. 
2. 
The 
involved 
substance/medication 
is capable 
of 
producing 
the 
symptoms in 
Criterion 
A. 
C. 
The 
disturbance 
is not 
better explained 
by a 
depressive 
disorder that 
is not 
substance/medication-induced. 
Such 
evidence 
of 
an 
independent 
depressive 
disorder could 
include 
the 
following: 
The 
symptoms preceded 
the 
onset 
of 
the 
substance/medication 
use; 
the 
symptoms persist 
for a 
substantial period 
of 
time 
(e.g., 
about 
1 
month) after the 
cessation 
of 
acute 
withdrawal or severe 
intoxication; 
or there 
is other evidence 
suggesting 
the 
existence 
of 
an 
independent 
non-substance/medication-induced 
depressive 
disorder (e.g., 
a 
history of 
recurrent 
non-substance/medicationrelated 
episodes). 


D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Note: 
This diagnosis should 
be 
made 
instead 
of 
a 
diagnosis of 
substance 
intoxication 
or substance 
withdrawal only when 
the 
symptoms in 
Criterion 
A 
predominate 
in 
the 
clinical picture 
and 
when 
they are 
sufficiently severe 
to 
warrant 



clinical attention. 
Coding 
note: 
The 
ICD-10-CM codes for the 
[specific substance/medication]-induced 
depressive 
disorders are 
indicated 
in 
the 
table 
below. 
Note 
that 
the 
ICD-10-CM code 
depends on 
whether or not 
there 
is a 
comorbid 
substance 
use 
disorder present 
for 
the 
same 
class of 
substance. 
In 
any case, 
an 
additional separate 
diagnosis of 
a 
substance 
use 
disorder is not 
given. 
If 
a 
mild 
substance 
use 
disorder is comorbid 
with 
the 
substance-induced 
depressive 
disorder, 
the 
4th 
position 
character is  1,  
and 
the 
clinician 
should 
record 
 mild 
[substance] 
use 
disorder  before 
the 
substance-
induced 
depressive 
disorder (e.g., 
 mild 
cocaine 
use 
disorder with 
cocaine-induced 
depressive 
disorder ). 
If 
a 
moderate 
or severe 
substance 
use 
disorder is comorbid 
with 
the 
substance-induced 
depressive 
disorder, 
the 
4th 
position 
character is  2,  
and 
the 
clinician 
should 
record 
 moderate 
[substance] 
use 
disorder  or  severe 
[substance] 
use 
disorder,  depending 
on 
the 
severity of 
the 
comorbid 
substance 
use 
disorder. 
If 
there 
is no 
comorbid 
substance 
use 
disorder (e.g., 
after a 
one-time 
heavy 
use 
of 
the 
substance), 
then 
the 
4th 
position 
character is  9,  and 
the 
clinician 
should 
record 
only the 
substance-induced 
depressive 
disorder. 


202 


ICD-10-CM 


With 
moderate 
or 
With 
mild 
use 
severe 
use 
Without 
use 
disorder 
disorder 
disorder 
Alcohol 
F10.14 
F10.24 
F10.94 
Phencyclidine 
F16.14 
F16.24 
F16.94 
Other 
hallucinogen 
F16.14 
F16.24 
F16.94 
Inhalant 
F18.14 
F18.24 
F18.94 
Opioid 
F11.14 
F11.24 
F11.94 
Sedative, 
hypnotic, 
or 
anxiolytic 
F13.14 
F13.24 
F13.94 
Amphetamine-type 
substance 
(or 
other 
stimulant) 
F15.14 
F15.24 
F15.94 
Cocaine 
F14.14 
F14.24 
F14.94 
Other 
(or 
unknown) 
substance 
F19.14 
F19.24 
F19.94 


Specify 
(see 
Table 
1 
in 
the 
chapter  Substance-Related 
and 
Addictive 
Disorders,  
which 
indicates whether  with 
onset 
during 
intoxication  and/or  with 
onset 
during 
withdrawal  applies to 
a 
given 
substance 
class; 
or specify 
 with 
onset 
after 
medication 
use ): 


With 
onset during 
intoxication: 
If 
criteria 
are 
met 
for intoxication 
with 
the 


substance 
and 
the 
symptoms develop 
during 
intoxication. 
With 
onset during 
withdrawal: 
If 
criteria 
are 
met 
for withdrawal from the 
substance 
and 
the 
symptoms develop 
during, 
or shortly after, 
withdrawal. 


With 
onset after medication 
use: 
If 
symptoms developed 
at 
initiation 
of 
medication, 
with 
a 
change 
in 
use 
of 
medication, 
or during 
withdrawal of 



medication. 


Recording Procedures 


The name of the substance/medication-induced depressive disorder begins with the specific 
substance (e.g., cocaine, dexamethasone) that 
is presumed to be causing the depressive 
symptoms. The diagnostic code is selected from 
the table included in the criteria set, which is 
based on the drug class and presence or absence of a comorbid substance use disorder. For 
substances that 
do not 
fit 
into any of the classes (e.g., dexamethasone), the code for  other (or 
unknown) substance  should be used; 
and in cases in which a substance is judged to be an 
etiological 
factor but 
the specific class of substance is unknown, the same code should also be 
used. 


When recording the name of the disorder, the comorbid substance use disorder (if any) is 
listed first, followed by the word  with,  followed by the name of the substance-induced 
depressive disorder, followed by the specification of onset 
(i.e., onset 
during intoxication, onset 
during withdrawal). For example, in the case of depressive symptoms occurring during 
withdrawal 
in a man with a severe cocaine use disorder, the diagnosis is F14.24 severe cocaine 
use disorder with cocaine-induced depressive disorder, with onset 
during withdrawal. A separate 
diagnosis of the comorbid severe cocaine use disorder is not 
given. If the substance-induced 
depressive disorder occurs without 
a comorbid substance use disorder (e.g., after a one-time 
heavy use of the substance), no accompanying substance use disorder is noted (e.g., F16.94 
phencyclidine-induced depressive disorder, with onset 
during intoxication). When more than one 
substance is judged to play a significant role in the development of depressive 


203 


mood symptoms, each should be listed separately (e.g., F15.24 severe methylphenidate use 
disorder with methylphenidate-induced depressive disorder, with onset 
during withdrawal; 
F19.94 dexamethasone-induced depressive disorder, with onset during intoxication). 


Diagnostic Features 


The essential 
feature of substance/medication-induced depressive disorder is a prominent 
and 
persistent 
disturbance in mood that 
predominates in the clinical 
picture and is characterized by 
depressed mood or markedly diminished interest 
or pleasure in all, or almost 
all, activities 
(Criterion A) that 
is due to the direct 
physiological 
effects of a substance (e.g., a drug of abuse, a 
medication, or a toxin exposure) (Criterion B). In order to meet 
criteria for the diagnosis, the 
depressive symptoms must 
have developed during or soon after substance intoxication or 
withdrawal 
or after exposure to or withdrawal 
from 
a medication, as evidenced by clinical 
history, physical 
examination, or laboratory findings (Criterion B1), and the involved 
substance/medication must 
be capable of producing the depressive symptoms (Criterion B2). In 
addition, the depressed symptoms are not 
better explained by a non-substance/medicationinduced 
depressive disorder. 


Evidence of an independent 
depressive disorder includes the observation that 
the depressive 
symptoms preceded the onset 
of substance/medication use, the depressive symptoms persist 
beyond a substantial 
period of time after the cessation of acute withdrawal 
or severe intoxication, 



or there is other evidence that 
suggests the existence of an independent 
non-
substance/medication-induced depressive disorder (Criterion C), such as a history of recurrent 
non-substance-induced depressive episodes. This diagnosis should not 
be made when symptoms 
occur exclusively during the course of a delirium 
(Criterion D). Finally, the diagnosis requires 
that 
the substance/medication-induced depressive symptoms cause clinically significant 
distress 
or impairment 
in social, occupational, or other important 
areas of functioning (Criterion E). The 
substance-induced depressive disorder diagnosis should be made instead of a diagnosis of 
substance intoxication or substance withdrawal 
only when the symptoms in Criterion A 
predominate in the clinical 
picture and are sufficiently severe to warrant 
independent 
clinical 
attention. 


The two categories of drugs of abuse most 
likely to cause a substance/medication-induced 
depressive disorder are depressants (e.g., intoxication with alcohol, benzodiazepines and other 
sedative, hypnotic, or anxiolytic drugs) and stimulants (e.g., withdrawal 
from 
amphetamine-type 
substances and cocaine). Some medications (e.g., steroids; 
antihypertensive medications such as 
clonidine, guanethidine, methyldopoa, and reserpine; 
interferon; 
L-dopa) are especially likely to 
cause substance/medication-induced depressive syndromes. Substances implicated in 
medication-induced depressive disorder, with varying degrees of evidence, include antibiotics, 
antiviral 
agents (efavirenz), cardiovascular agents (beta-blockers and calcium 
channel 
blockers, 
retinoic acid derivatives (isotretinoin), antidepressants, anticonvulsants, antimigraine agents 
(triptans), antipsychotics, hormonal 
agents (corticosteroids, oral 
contraceptives, gonadotropinreleasing 
hormone agonists, tamoxifen), chemotherapeutic drugs, and smoking cessation agents 
(varenicline). This list is likely to grow as new compounds are synthesized. 


Clear clinical 
histories and careful 
judgment 
are essential 
in determining whether the 
substance of abuse or medication is truly associated with induced depressive symptoms or 
whether the symptoms are better understood as constituting an independent 
depressive disorder. 
A diagnosis of a substance/medication-induced depressive disorder is most 
likely if the 
individual 
was taking high doses of a relevant 
drug of abuse or medication and there is no past 
history of independent 
depressive episodes. For example, a depressive episode that 
developed in 
the context 
of heavy use of a relevant 
substance of abuse or within the first 
several 
weeks of 
beginning alpha-methyldopa (an antihypertensive agent) in an individual 
with no history of 
major depressive disorder would qualify for the diagnosis of a substance- or medication-induced 
depressive disorder. In some cases, a previously established condition (e.g., major depressive 
disorder, recurrent) can recur while the individual is 


204 


coincidentally taking a drug or medication that 
has the capacity to cause depressive 
symptoms (e.g., alcohol 
and/or stimulants in context 
of heavy use, L-dopa, oral 
contraceptives). 
In all 
of these cases, the clinician must 
make a judgment 
as to whether the medication is 
causative in this particular situation. 


A substance/medication-induced depressive disorder is distinguished from 
an independent 
depressive disorder by the onset 
or course, or by other factors associated with the substance or 
medication use. There must 
be evidence from 
the history, physical 
examination, or laboratory 
findings of use of a drug of abuse or a medication that 
is capable of producing depressive 
symptoms after exposure to, withdrawal 
from, or intoxication with that 
substance prior to the 



onset 
of the depressive disorder. The neurochemical 
changes associated with intoxication and 
withdrawal 
states for some substances can be relatively protracted, and thus intense depressive 
symptoms can last 
for a longer period after the cessation of substance use and still 
be consistent 
with a diagnosis of a substance/medication-induced depressive disorder. 


Prevalence 


The lifetime rate of alcohol- and stimulant-induced depressive episodes has been reported to be 
40% or higher among individuals with relevant 
substance use disorders. However, in a nationally 
representative U.S. adult 
population, the lifetime prevalence of substance/medication-induced 
depressive disorder in the absence of a lifetime history of non-substance-induced depressive 
disorder was only 0.26%. These data indicate that 
special 
care must 
be taken to search for and 
address substance-induced conditions in individuals with alcohol and stimulant use disorders. 


Development and Course 


A depressive disorder associated with the use of substances (e.g., alcohol, amphetamine-type 
substances and/or cocaine, or a prescribed treatment 
for medical 
conditions) must 
have its onset 
while the individual 
is using the substance or during withdrawal, if there is a withdrawal 
syndrome associated with the substance. Most 
often, the depressive disorder has its onset 
within 
the first few weeks or 1 month of heavy use of the substance. Once the substance is discontinued, 
the depressive symptoms usually remit 
within days to several 
weeks, depending on the half-life 
of the substance/medication and the presence of a withdrawal 
syndrome. If symptoms persist 
4 
weeks beyond the expected time course of withdrawal 
of a particular substance/medication, other 
causes for the depressive mood symptoms should be considered. 


There are several 
prospective controlled trials examining the association of depressive 
symptoms with use of a prescribed medication, but 
most 
reports on this topic involve 
retrospective series of individuals entering treatment, or participants in large cross-sectional 
studies. More studies exist 
regarding the clinical 
course of alcohol- and illicit 
drug induced 
depressions, and most 
support 
the contention that 
the substance-induced conditions are very 
likely to fade away within a relatively short 
time after abstinence. Equally important 
are 
indications that 
individuals with significant 
residual 
depressive symptoms following treatment 
for substance use disorders have a greater likelihood of relapse into their substance use. 


Risk and Prognostic Factors 


Risk factors for substance-induced depressive disorder include a history of antisocial 
personality 
disorder, schizophrenia, and bipolar disorder; 
a history of stressful 
life events in the past 
12 
months; 
a history of prior drug-induced depressions; 
and a family history of substance use 
disorders. In addition, neurochemical 
changes associated with alcohol 
and other drugs of abuse 
often contribute to depressive and anxiety symptoms during withdrawal 
that 
subsequently 
influence ongoing substance use and reduce the likelihood of remission of substance use 
disorders. The course of substance-induced depressive disorder may be worsened by social-
structural adversity associated with poverty, racism, and marginalization. 


205 



Sex- and Gender-Related Diagnostic Issues 


Among individuals with a substance use disorder, the risk for developing a substance-induced 
depressive disorder appears to be similar in men and women. 


Diagnostic Markers 


Laboratory assays of the suspected substance in the blood or urine are of limited value in 
identifying substance-induced depressive disorder because blood and urine levels are often 
negative when an individual 
comes for evaluation, reflecting the fact 
that 
substance-induced 
depressions can last 
for up to 4 weeks after use of the drug of abuse or medication has ceased. 
Therefore, a positive test 
value only means that 
an individual 
has had recent 
experience with a 
substance but 
by itself does not 
establish a time course or other characteristics that 
are likely to 
be associated with substance-induced depressive disorder. However, as is true of most 
mental 
disorders, the most 
important 
data in diagnosing these conditions come from 
a detailed clinical 
history and the mental status examination. 


Association With Suicidal 
Thoughts or Behavior 


The risk of suicide attempts is higher among individuals with possible alcohol 
use disorder 
experiencing depressive episodes, whether substance induced or independent 
of substances, as 
compared with control subjects. 


Differential 
Diagnosis 


Substance 
intoxication 
and 
withdrawal. 
Depressive symptoms occur commonly in substance 
intoxication and substance withdrawal. A diagnosis of substance-induced depressive disorder 
should be made instead of a diagnosis of substance intoxication or substance withdrawal 
when 
the mood symptoms are sufficiently severe to warrant 
independent 
clinical 
attention. For 
example, dysphoric mood is a characteristic feature of cocaine withdrawal. Substance-induced 
depressive disorder with onset 
during withdrawal 
should be diagnosed instead of cocaine 
withdrawal 
only if the mood disturbance in Criterion A predominates in the clinical 
picture and 
is sufficiently severe to be a separate focus of attention and treatment. 


Independent 
depressive 
disorder. 
A substance/medication-induced depressive disorder is 
distinguished from an independent depressive disorder by the fact that even though a substance is 
taken in high enough amounts to be possibly etiologically related to the symptoms, if the 
depressive syndrome is observed at 
times other than when the substance or medication is being 
used, it should be diagnosed as an independent depressive disorder. 


Depressive 
disorder due 
to 
another medical 
condition. 


Because individuals with medical 
conditions 
often take medications for those conditions, the clinician must 
consider the possibility that 
the 
mood symptoms are caused by the physiological 
consequences of the medical 
condition rather 
than the medication, in which case depressive disorder due to another medical 
condition is 
diagnosed. The history often provides the primary basis for such a judgment. At 
times, a change 
in the treatment 
for the medical 
condition (e.g., medication substitution or discontinuation) may 
be needed to determine empirically whether the medication is the causative agent. If the clinician 
has ascertained that the disturbance is a function of both another medical condition and substance 
use or withdrawal, then both diagnoses (i.e., depressive disorder due to another medical 



condition and substance/medication-induced depressive disorder) may be given. When there is 
insufficient 
evidence to determine whether the depressive symptoms are associated with 
substance (including a medication) ingestion or withdrawal 
or with another medical 
condition or 
are independent 
(i.e., not 
a function of either a substance or another medical 
condition), a 
diagnosis of other specified depressive disorder or unspecified depressive disorder is indicated. 


206 


Comorbidity 


In one study using DSM-IV, comparing individuals with independent 
major depressive disorder 
and no comorbid substance use disorder and individuals with substance/medication-induced 
depressive disorder, those with substance/medication-induced depressive disorder had higher 
rates of comorbidity with any DSM-IV mental 
disorder; 
were more likely to have specific 
disorders of tobacco use disorder, gambling disorder, and antisocial 
personality disorder; 
and 
were less likely to have persistent 
depressive disorder. Compared with individuals with major 
depressive disorder and a comorbid substance use disorder, individuals with 
substance/medication-induced depressive disorder are more likely to have alcohol 
or other 
substance use disorder; however, they are less likely to have persistent depressive disorder. 


Depressive Disorder Due to 
Another Medical 
Condition 


Diagnostic Criteria 


A. 
A 
prominent 
and 
persistent 
disturbance 
in 
mood 
that 
predominates in 
the 
clinical 
picture 
and 
is characterized 
by depressed 
mood 
or markedly diminished 
interest 
or pleasure 
in 
all, 
or almost 
all, 
activities. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
that 
the 
disturbance 
is the 
direct 
pathophysiological consequence 
of 
another 
medical condition. 
C. 
The 
disturbance 
is not 
better explained 
by another mental disorder (e.g., 
adjustment 
disorder, 
with 
depressed 
mood, 
in 
which 
the 
stressor is a 
serious 
medical condition). 
D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Coding 
note: 
The 
ICD-10-CM code 
depends on 
the 
specifier (see 
below). 
Specify 
if: 
F06.31 
With 
depressive 
features: 
Full criteria 
are 
not 
met 
for a 
major 
depressive 
episode. 


F06.32 
With 
major depressive like 
episode: 
Full criteria 
are 
met 
(except 
Criterion 
C) for a 
major depressive 
episode. 



F06.34 
With 
mixed 
features: 
Symptoms of 
mania 
or hypomania 
are 
also 


present 
but 
do 
not 
predominate 
in 
the 
clinical picture. 
Coding 
note: 
Include 
the 
name 
of 
the 
other medical condition 
in 
the 
name 
of 
the 
mental disorder (e.g., 
F06.31 
depressive 
disorder due 
to 
hypothyroidism, 
with 
depressive 
features). 
The 
other medical condition 
should 
also 
be 
coded 
and 
listed 
separately immediately before 
the 
depressive 
disorder due 
to 
the 
medical condition 
(e.g., 
E03.9 
hypothyroidism; 
F06.31 
depressive 
disorder due 
to 
hypothyroidism, 
with 
depressive 
features). 


Diagnostic Features 


The essential 
feature of depressive disorder due to another medical 
condition is a prominent 
and 
persistent 
period of depressed mood or markedly diminished interest 
or pleasure in all, or almost 
all, activities that 
predominates in the clinical 
picture (Criterion A) and that 
is thought 
to be due 
to the physiological 
effects of another medical 
condition (Criterion B). In determining whether 
the mood disturbance is due to another medical 
condition, the clinician must 
first 
establish the 
presence of another medical 
condition. Further, the clinician must 
establish that 
the mood 
disturbance is etiologically related to another medical condition through a physiological 


207 


mechanism. A careful 
and comprehensive assessment 
of multiple factors is necessary to make 
this judgment. Although there are no infallible guidelines for determining whether the 
relationship between the mood disturbance and another medical 
condition is etiological, several 
considerations provide some guidance in this area. One consideration is the presence of a 
temporal 
association between the onset, exacerbation, or remission of another medical 
condition 
and that 
of the mood disturbance. A second consideration is the presence of features that 
are 
atypical 
of independent 
depressive disorders (e.g., atypical 
age at 
onset 
or course or absence of 
family history). Evidence from 
the literature that 
suggests that 
there can be a direct 
association 
between another medical 
condition in question and the development 
of mood symptoms can 
provide a useful context in the assessment of a particular situation. 


Associated Features 


Etiology (i.e., a causal 
relationship to another medical 
condition based on best 
clinical 
evidence) 
is the key variable in depressive disorder due to another medical 
condition. The listing of the 
medical 
conditions that 
are said to be able to induce major depression is never complete, and the 
clinician s best judgment is the essence of this diagnosis. 


There are clear associations, as well 
as some neuroanatomical 
correlates, of depression with 
cerebrovascular accident 
(CVA), Huntington s disease, Parkinson s disease, and traumatic brain 
injury (TBI). Among the neuroendocrine conditions most 
closely associated with depression are 
Cushing s syndrome and hypothyroidism. Autoimmune disorders, such systemic lupus 
erythematosus, and deficiencies of certain vitamins, such as vitamin B12, have also been linked 


to depression. There are numerous other conditions thought 
to be associated with depression, 
such as multiple sclerosis. However, the literature s support 
for a causal 
association is greater 



with some conditions than with others. Currently, there is support 
for a direct 
pathophysiological 
mechanism 
for depressive symptoms in focal 
lesions (CVA, TBI, neoplasm) affecting certain 
brain regions, Parkinson s disease, Huntington s disease, hypothyroidism, Cushing s syndrome, 
and pancreatic cancer. 


Prevalence 


Sex differences in prevalence depend somewhat 
on the sex difference associated with the 
medical 
condition (e.g., systemic lupus erythematosus is more common in women; 
stroke is 
somewhat more common in middle-age men compared with women). 


Development and Course 


Following stroke, the onset 
of depression appears to be acute, occurring within a few days of the 
CVA in the largest 
case series. However, in some cases, onset 
of the depression is weeks to 
months following the CVA. In the largest 
series, the duration of the major depressive episode 
following stroke was 9 11 months on average. With Parkinson s disease and Huntington s 
disease, depression often precedes the major motor impairments and cognitive impairments 
associated with each condition. This is more prominently the case for Huntington s disease, in 
which depression is considered to be the first 
neuropsychiatric symptom. There is some 
observational 
evidence that 
depression is less common as the neurocognitive disorder due to 
Huntington s disease progresses. In some individuals with static brain injuries and other central 
nervous system 
diseases, mood symptoms may be episodic (i.e., recurring) over the course of the 
disorder. In Cushing s syndrome and hypothyroidism, depression can be an early manifestation 
of the disease. In pancreatic cancer, depression often precedes other features. 


Risk and Prognostic Factors 


The risk of acute onset 
of a major depressive disorder following a CVA (within 1 day to a week 
of the event) appears to be strongly correlated with lesion location, with greatest 
risk associated 
with left frontal strokes and least risk apparently associated with right frontal lesions 


208 


in those individuals who present 
within days of the stroke. The association with frontal 
regions 
and laterality is not 
observed in depressive states that 
occur in the 2 6 months following stroke, 
perhaps indicative of later depressive symptoms representing major depressive disorder, 
adjustment 
disorder, or demoralization. In individuals with Parkinson s disease, early age at 
onset, greater burden of motor symptoms, and longer duration of the disease have been 
associated with depression. Risk of depression after TBI has been associated with female gender, 
prior depressive disorder, early psychiatric symptoms following injury, lower brain volume, and 
unemployment. 


Sex- and Gender-Related Diagnostic Issues 


Women may be at 
differentially higher risk for developing depression in the setting of 
cardiovascular disease, particularly poststroke. 



Diagnostic Markers 


Diagnostic markers pertain to those associated with the medical 
condition (e.g., steroid levels in 
blood or urine to help corroborate the diagnosis of Cushing s disease, which can be associated 
with manic or depressive syndromes). 


Association With Suicidal 
Thoughts or Behavior 


There are no epidemiological 
studies that 
provide evidence to differentiate the risk of suicide 
from 
a major depressive episode due to another medical 
condition compared with the risk from 
a 
major depressive episode in general. There are case reports of suicides in association with major 
depressive episodes associated with another medical 
condition. There is a clear association 
between serious medical 
illnesses and suicide, particularly shortly after onset 
or diagnosis of the 
illness. Thus, it 
would be prudent 
to assume that 
the risk of suicide for major depressive episodes 
associated with medical 
conditions is not 
less than that 
for other forms of major depressive 
episode, and might even be greater. 


Differential 
Diagnosis 


Depressive 
disorders 
not 
due 
to 
another medical 
condition. 


Determination of whether a medical 
condition accompanying a depressive disorder is causing the disorder depends on a) the absence 
of an episode(s) of depressive episodes prior to the onset 
of the medical 
condition, b) the 
probability that 
the associated medical 
condition has a potential 
to promote or cause a depressive 
disorder, and c) a course of the depressive symptoms shortly after the onset 
or worsening of the 
medical 
condition, especially if the depressive symptoms remit 
near the time that 
the medical 
disorder is effectively treated or remits. 


Medication-induced 
depressive 
disorder. 
An important 
caveat 
is that 
some medical 
conditions are 
treated with medications (e.g., steroids or alpha-interferon) that 
can induce depressive or manic 
symptoms. In these cases, clinical 
judgment, based on all 
the evidence in hand, is the best 
way to 
try to separate the most 
likely and/or the most 
important 
of two etiological 
factors (i.e., 
association with the medical condition vs. a substance-induced syndrome). 
Delirium and 
major or mild 
neurocognitive 
disorder. 
A separate diagnosis of depressive disorder due 


to another medical 
condition is not 
given if the depressive disturbance occurs exclusively during 
the course of a delirium. However, a diagnosis of depressive disorder due to another medical 
condition may be given in addition to a diagnosis of major or mild neurocognitive disorder if the 
depressive disturbance is judged to be a physiological 
consequence of the pathological 
process 
causing the neurocognitive disorder and if symptoms of depression are a prominent 
part 
of the 
clinical presentation. 


Adjustment 
disorders. 
It 
is important 
to differentiate a depressive episode from 
an adjustment 
disorder, as the onset of the medical condition is in itself a life stressor that could 


209 


bring on either an adjustment 
disorder or an episode of major depression. The major 
differentiating elements are the pervasiveness of the depressive picture and the number and 
quality of the depressive symptoms that 
the individual 
reports or demonstrates on the mental 



status examination. The differential 
diagnosis of the associated medical 
conditions is relevant 
but 


largely beyond the scope of the present manual. 
Demoralization. 
Demoralization is a common reaction to chronic medical 
illness. It 
is marked by 
a sense of subjective incompetence, helplessness, and hopelessness, and a desire to give up. It 
is 
often accompanied by depressive symptoms such as low mood and fatigue. Demoralization 
typically lacks the anhedonia associated with depressive disorder due to another medical 
condition, and individuals will 
generally find pleasure in previously meaningful 
activities and be 
able to experience moments of happiness. 


Comorbidity 


Conditions comorbid with depressive disorder due to another medical 
condition are those 
associated with the medical 
conditions of etiological 
relevance. It 
has been noted that 
delirium 
can occur before or along with depressive symptoms in individuals with a variety of medical 
conditions, such as Cushing s disease. The association of anxiety symptoms, usually generalized 
symptoms, is common in depressive disorders, regardless of cause. 


Other Specified 
Depressive Disorder 


F32.89 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
depressive 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
depressive 
disorders diagnostic class 
and 
do 
not 
meet 
criteria 
for adjustment 
disorder with 
depressed 
mood 
or adjustment 
disorder with 
mixed 
anxiety and 
depressed 
mood. 
The 
other specified 
depressive 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific 
depressive 
disorder. 
This is done 
by recording 
 other specified 
depressive 
disorder  
followed 
by the 
specific reason 
(e.g., 
 short-duration 
depressive 
episode ). 


Examples of 
presentations that 
can 
be 
specified 
using 
the 
 other specified  
designation 
include 
the 
following: 


1. 
Recurrent brief depression: 
Concurrent 
presence 
of 
depressed 
mood 
and 
at 
least 
four other symptoms of 
depression 
for 2 13 
days at 
least 
once 
per month 
(not 
associated 
with 
the 
menstrual cycle) for at 
least 
12 
consecutive 
months in 
an 
individual whose 
presentation 
has never met 
criteria 
for any other depressive 
or bipolar disorder and 
does not 
currently meet 
active 
or residual criteria 
for any 
psychotic disorder. 
2. 
Short-duration 
depressive 
episode 
(4 13 
days): 
Depressed 
affect 
and 
at 
least 
four of 
the 
other eight 
symptoms of 
a 
major depressive 
episode 
associated 
with 
clinically significant 
distress or impairment 
that 
persists for more 
than 
4 
days, 
but 
less than 
14 
days, 
in 
an 
individual whose 
presentation 
has never met 
criteria 
for 
any other depressive 
or bipolar disorder, 
does not 
currently meet 
active 
or 

residual criteria 
for any psychotic disorder, 
and 
does not 
meet 
criteria 
for 
recurrent 
brief 
depression. 


3. 
Depressive 
episode 
with 
insufficient symptoms: 
Depressed 
affect 
and 
at 
least 
one 
of 
the 
other eight 
symptoms of 
a 
major depressive 
episode 
associated 
with 
clinically significant 
distress or impairment 
that 
persist 
for at 
least 
2 
weeks in 
an 
individual whose 
presentation 
has never met 
criteria 
for any other depressive 
or bipolar disorder, 
does not 
currently meet 
active 
or residual criteria 
for any 
psychotic disorder, 
and 
does not 
meet 
criteria 
for mixed 
anxiety and 
depressive 
disorder symptoms. 
210 


4. 
Major depressive 
episode 
superimposed 
on 
schizophrenia, 
schizophreniform 
disorder, 
delusional disorder, 
or other specified 
and 
unspecified 
schizophrenia 
spectrum and 
other psychotic disorder. 
Note: 
Major depressive 
episodes that 
are 
part 
of 
schizoaffective 
disorder do 
not 
merit 
an 
additional diagnosis of 
other 
specified 
depressive 
disorder. 
Unspecified 
Depressive Disorder 


F32.A 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
depressive 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
depressive 
disorders diagnostic class 
and 
do 
not 
meet 
criteria 
for adjustment 
disorder with 
depressed 
mood 
or adjustment 
disorder with 
mixed 
anxiety and 
depressed 
mood. 
The 
unspecified 
depressive 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify 
the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific depressive 
disorder, 
and 
includes presentations for which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room settings). 


Unspecified 
Mood 
Disorder 


F39 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
mood 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
at 
the 
time 
of 
the 
evaluation 
meet 
the 
full criteria 
for any of 
the 
disorders in 
either the 
bipolar or the 
depressive 
disorders diagnostic classes and 
in 
which 
it 
is difficult 
to 



choose 
between 
unspecified 
bipolar and 
related 
disorder and 
unspecified 
depressive 
disorder (e.g., 
acute 
agitation). 


Specifiers for Depressive Disorders 


Specify 
if: 
With 
anxious 
distress: 
Anxious distress is defined 
as the 
presence 
of 
at 
least 
two 
of 
the 
following 
symptoms during 
the 
majority of 
days of 
the 
current 
major 
depressive 
episode 
(or the 
most 
recent 
major depressive 
episode 
if 
major 
depressive 
disorder is currently in 
partial or full remission) or current 
persistent 
depressive 
disorder: 


1. 
Feeling 
keyed 
up 
or tense. 
2. 
Feeling 
unusually restless. 
3. 
Difficulty concentrating 
because 
of 
worry. 
4. 
Fear that 
something 
awful may happen. 
5. 
Feeling 
that 
the 
individual might 
lose 
control of 
himself 
or herself. 
Specify 
current 
severity: 
Mild: 
Two 
symptoms. 
Moderate: 
Three 
symptoms. 
Moderate-severe: 
Four or five 
symptoms. 
Severe: 
Four or five 
symptoms and 
with 
motor agitation. 


Note: 
Anxious distress has been 
noted 
as a 
prominent 
feature 
of 
both 
bipolar 
and 
major depressive 
disorder in 
both 
primary care 
and 
specialty mental 
health 


211 


settings. 
High 
levels of 
anxiety have 
been 
associated 
with 
higher suicide 
risk, 
longer duration 
of 
illness, 
and 
greater likelihood 
of 
treatment 
nonresponse. 
As 
a 
result, 
it 
is clinically useful to 
specify accurately the 
presence 
and 
severity 
levels of 
anxious distress for treatment 
planning 
and 
monitoring 
of 
response 
to 
treatment. 


With 
mixed 
features: 


A. 
At 
least 
three 
of 
the 
following manic/hypomanic symptoms are 
present 
during 
the 
majority of 
days of 
the 
current 
major depressive 
episode 
(or the 
most 
recent 
major depressive 
episode 
if 
major depressive 
disorder is currently in 
partial or full remission): 
1. 
Elevated, 
expansive 
mood. 
2. 
Inflated 
self-esteem or grandiosity. 
3. 
More 
talkative 
than 
usual or pressure 
to 
keep 
talking. 

4. 
Flight 
of 
ideas or subjective 
experience 
that 
thoughts are 
racing. 
5. 
Increase 
in 
energy or goal-directed 
activity (either socially, 
at 
work or 
school, 
or sexually). 
6. 
Increased 
or excessive 
involvement 
in 
activities that 
have 
a 
high 
potential 
for painful consequences (e.g., 
engaging 
in 
unrestrained 
buying 
sprees, 
sexual indiscretions, 
or foolish 
business investments). 
7. 
Decreased 
need 
for sleep 
(feeling 
rested 
despite 
sleeping 
less than 
usual; 
to 
be 
contrasted 
with 
insomnia). 
B. 
Mixed 
symptoms are 
observable 
by others and 
represent 
a 
change 
from the 
person s usual behavior. 
C. 
For individuals whose 
symptoms meet 
full criteria 
for either mania 
or 
hypomania, 
the 
diagnosis should 
be 
bipolar I 
or bipolar II 
disorder. 
D. 
The 
mixed 
symptoms are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication 
or other treatment). 
Note: 
Mixed 
features associated 
with 
a 
major depressive 
episode 
have 
been 
found 
to 
be 
a 
significant 
risk factor for the 
development 
of 
bipolar I 
or bipolar II 
disorder. 
As a 
result, 
it 
is clinically useful to 
note 
the 
presence 
of 
this specifier 
for treatment 
planning 
and 
monitoring 
of 
response 
to 
treatment. 


With 
melancholic 
features: 


A. 
One 
of 
the 
following 
is present 
during 
the 
most 
severe 
period 
of 
the 
current 
major depressive 
episode 
(or the 
most 
recent 
major depressive 
episode 
if 
major depressive 
disorder is currently in 
partial or full remission): 
1. 
Loss of 
pleasure 
in 
all, 
or almost 
all, 
activities. 
2. 
Lack of 
reactivity to 
usually pleasurable 
stimuli (does not 
feel much 
better, 
even 
temporarily, 
when 
something 
good 
happens). 
B. 
Three 
(or more) of 
the 
following: 
1. 
A 
distinct 
quality of 
depressed 
mood 
characterized 
by profound 
despondency, 
despair, 
and/or moroseness or by so-called 
empty mood. 
2. 
Depression 
that 
is regularly worse 
in 
the 
morning. 
3. 
Early-morning 
awakening 
(i.e., 
at 
least 
2 
hours before 
usual awakening). 
4. 
Marked 
psychomotor agitation 
or retardation. 
5. 
Significant 
anorexia 
or weight 
loss. 
6. 
Excessive 
or inappropriate 
guilt. 
Note: 
The 
specifier  with 
melancholic features  is applied 
if 
these 
features are 
present 
at 
the 
most 
severe 
stage 
of 
the 
episode. 
There 
is a 
near-complete 
absence 
of 
the 


212 


capacity for pleasure, 
not 
merely a 
diminution. 
A 
guideline 
for evaluating 
the 
lack 



 
 
 
 
 
215 



Anxiety Disorders 


Anxiety disorders 
include disorders that 
share features of excessive fear and anxiety and 
related behavioral 
disturbances. Fear 
is the emotional 
response to real 
or perceived imminent 
threat, whereas anxiety 
is anticipation of future threat. Obviously, these two states overlap, but 
they also differ, with fear more often associated with surges of autonomic arousal 
necessary for 
fight 
or flight, thoughts of immediate danger, and escape behaviors, and anxiety more often 
associated with muscle tension and vigilance in preparation for future danger and cautious or 
avoidant 
behaviors. Sometimes the level 
of fear or anxiety is reduced by pervasive avoidance 
behaviors. Panic attacks 
feature prominently within the anxiety disorders as a particular type of 
fear response. Panic attacks are not 
limited to anxiety disorders but 
rather can be seen in other 
mental disorders as well. 


The anxiety disorders differ from 
one another in the types of objects or situations that 
induce 
fear, anxiety, or avoidance behavior, and the associated cognition. Thus, while the anxiety 
disorders tend to be highly comorbid with each other, they can be differentiated by close 
examination of the types of situations that 
are feared or avoided and the content 
of the associated 
thoughts or beliefs. 


Anxiety disorders differ from 
developmentally normative fear or anxiety by being excessive 
or persisting beyond developmentally appropriate periods. They differ from 
transient 
fear or 
anxiety, often stress-induced, by being persistent 
(e.g., typically lasting 6 months or more), 
although the criterion for duration is intended as a general 
guide with allowance for some degree 
of flexibility and is sometimes of shorter duration in children (as in separation anxiety disorder 
and selective mutism). Since individuals with anxiety disorders typically overestimate the danger 
in situations they fear or avoid, the primary determination of whether the fear or anxiety is 
excessive or out 
of proportion is made by the clinician, taking cultural 
contextual 
factors into 
account. Many of the anxiety disorders develop in childhood and tend to persist 
if not 
treated. 
Most 
occur more frequently in girls than in boys (approximately 2:1 ratio). Each anxiety disorder 
is diagnosed only when the symptoms are not 
attributable to the physiological 
effects of a 
substance/medication or to another medical 
condition or are not 
better explained by another 
mental disorder. 


The chapter is arranged developmentally, with disorders sequenced according to the typical 
age at 
onset. The individual 
with separation anxiety disorder is fearful 
or anxious about 
separation from 
attachment 
figures to a degree that 
is developmentally inappropriate. There is 
persistent 
fear or anxiety about 
harm 
coming to attachment 
figures and events that 
could lead to 
loss of or separation from 
attachment 
figures and reluctance to go away from 
attachment 
figures, 
as well 
as nightmares and physical 
symptoms of distress. Although the symptoms often develop 
in childhood, they can be expressed throughout 
adulthood as well 
in the absence of a history of 
childhood separation anxiety disorder. 


Selective mutism 
is characterized by a consistent 
failure to speak in social 
situations in which 



there is an expectation to speak (e.g., school) even though the individual 
speaks in other 
situations. The failure to speak has significant 
consequences on achievement 
in academic or 
occupational settings or otherwise interferes with normal social communication. 


216 


Individuals with specific phobia are fearful 
or anxious about 
or avoidant 
of circumscribed 
objects or situations. A specific cognition is not 
featured in this disorder, as it 
is in other anxiety 
disorders. The fear, anxiety, or avoidance is almost 
always immediately induced by the phobic 
situation, to a degree that 
is persistent 
and out 
of proportion to the actual 
risk posed. There are 
various types of specific phobias: 
animal; 
natural 
environment; 
blood-injection-injury; 
situational; and other situations. 


In social 
anxiety disorder, the individual 
is fearful 
or anxious about 
or avoidant 
of social 
interactions and situations that 
involve the possibility of being scrutinized. These include social 
interactions such as meeting unfamiliar people, situations in which the individual 
may be 
observed eating or drinking, and situations in which the individual 
performs in front 
of others. 
The cognition is of being negatively evaluated by others, by being embarrassed, humiliated, or 
rejected, or offending others. 


In panic disorder, the individual 
experiences recurrent 
unexpected panic attacks and is 
persistently concerned or worried about 
having more panic attacks or changes his or her behavior 
in maladaptive ways because of the panic attacks (e.g., avoidance of exercise or of unfamiliar 
locations). Panic attacks are abrupt 
surges of intense fear or intense discomfort 
that 
reach a peak 
within minutes, accompanied by physical 
and/or cognitive symptoms. Limited-symptom 
panic 
attacks include fewer than four symptoms. Panic attacks may be expected, 
such as in response to 
a typically feared object 
or situation, or unexpected, 
meaning that 
the panic attack occurs for no 
apparent 
reason. Panic attacks function as a marker and prognostic factor for severity of 
diagnosis, course, and comorbidity across an array of disorders, including, but 
not 
limited to, 
anxiety, substance use, depressive, and psychotic disorders. The specifier  with panic attacks  
may therefore be used for panic attacks that 
occur in the context 
of any anxiety disorder, as well 
as other mental disorders (e.g., depressive disorders, posttraumatic stress disorder). 


Individuals with agoraphobia are fearful 
and anxious in many different 
situations, and the 
diagnostic criteria require symptoms in two or more of the following: using public transportation, 
being in open spaces, being in enclosed places, standing in line or being in a crowd, or being 
outside of the home alone in other situations. The individual 
fears these situations because of 
thoughts that 
escape might 
be difficult 
or help might 
not 
be available in the event 
of developing 
panic-like symptoms or other incapacitating or embarrassing symptoms. These situations 
consistently induce fear or anxiety and are often avoided or require the presence of a companion. 


The key features of generalized anxiety disorder are persistent 
and excessive anxiety and 
worry about 
various domains, including work and school 
performance, that 
the individual 
finds 
difficult 
to control. In addition, the individual 
experiences physical 
symptoms, including 
restlessness or feeling keyed up or on edge; 
being easily fatigued; 
difficulty concentrating or 
mind going blank; irritability; muscle tension; and sleep disturbance. 


Substance/medication-induced anxiety disorder involves anxiety due to substance 
intoxication or withdrawal 
or to a medication treatment. In anxiety disorder due to another 
medical 
condition, anxiety symptoms are the physiological 
consequence of another medical 



condition. 


Disorder-specific scales are available to better characterize the severity of each anxiety 
disorder and to capture change in severity over time. For ease of use, particularly for individuals 
with more than one anxiety disorder, these scales have been developed to have the same format 
(but 
different 
focus) across the anxiety disorders, with ratings of behavioral 
symptoms, cognitive 
symptoms, and physical symptoms relevant to each disorder. 


Individuals with anxiety may be more likely to have suicidal 
thoughts, attempt 
suicide, and 
die by suicide than those without 
anxiety. Panic disorder, generalized anxiety disorder, and 
specific phobia have been identified as the anxiety disorders most 
strongly associated with a 
transition from suicidal thoughts to suicide attempt. 


217 


Separation 
Anxiety Disorder 


Diagnostic Criteria 
F93.0 


A. 
Developmentally inappropriate 
and 
excessive 
fear or anxiety concerning 
separation 
from those 
to 
whom the 
individual is attached, 
as evidenced 
by at 
least 
three 
of 
the 
following: 
1. 
Recurrent 
excessive 
distress when 
anticipating 
or experiencing 
separation 
from home 
or from major attachment 
figures. 
2. 
Persistent 
and 
excessive 
worry about 
losing 
major attachment 
figures or 
about 
possible 
harm to 
them, 
such 
as illness, 
injury, 
disasters, 
or death. 
3. 
Persistent 
and 
excessive 
worry about 
experiencing 
an 
untoward 
event 
(e.g., 
getting 
lost, 
being 
kidnapped, 
having 
an 
accident, 
becoming 
ill) that 
causes 
separation 
from a 
major attachment 
figure. 
4. 
Persistent 
reluctance 
or refusal to 
go 
out, 
away from home, 
to 
school, 
to 
work, 
or elsewhere 
because 
of 
fear of 
separation. 
5. 
Persistent 
and 
excessive 
fear of 
or reluctance 
about 
being 
alone 
or without 
major attachment 
figures at 
home 
or in 
other settings. 
6. 
Persistent 
reluctance 
or refusal to 
sleep 
away from home 
or to 
go 
to 
sleep 
without 
being 
near a 
major attachment 
figure. 
7. 
Repeated 
nightmares involving 
the 
theme 
of 
separation. 
8. 
Repeated 
complaints of 
physical symptoms (e.g., 
headaches, 
stomachaches, 
nausea, 
vomiting) when 
separation 
from major attachment 
figures occurs or 
is anticipated. 
B. 
The 
fear, 
anxiety, 
or avoidance 
is persistent, 
lasting 
at 
least 
4 
weeks in 
children 
and 
adolescents and 
typically 6 
months or more 
in 
adults. 
C. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
academic, 
occupational, 
or other important 
areas of 
functioning. 

D. 
The 
disturbance 
is not 
better explained 
by another mental disorder, 
such 
as 
refusing 
to 
leave 
home 
because 
of 
excessive 
resistance 
to 
change 
in 
autism 
spectrum disorder; 
delusions or hallucinations concerning 
separation 
in 
psychotic disorders; 
refusal to 
go 
outside 
without 
a 
trusted 
companion 
in 
agoraphobia; 
worries about 
ill health 
or other harm befalling 
significant 
others in 
generalized 
anxiety disorder; 
or concerns about 
having 
an 
illness in 
illness 
anxiety disorder. 
Diagnostic Features 


The essential 
feature of separation anxiety disorder is excessive fear or anxiety concerning 
separation from 
home or attachment 
figures. The anxiety exceeds what 
may be expected given 
the individual s developmental 
level 
(Criterion A). Individuals with separation anxiety disorder 
have symptoms that 
meet 
at 
least 
three of the following criteria: 
They experience recurrent 
excessive distress when separation from 
home or major attachment 
figures is anticipated or 
occurs (Criterion A1). They worry about 
the well-being or death of attachment 
figures, 
particularly when separated from 
them, and they need to know the whereabouts of their 
attachment 
figures and want 
to stay in touch with them 
(Criterion A2). They also worry about 
untoward events to themselves, such as getting lost, being kidnapped, or having an accident, that 
would keep them 
from 
ever being reunited with their major attachment 
figure (Criterion A3). 
Individuals with separation anxiety disorder are reluctant 
or refuse to go out 
by themselves 
because of separation fears (Criterion A4). They have 


218 


persistent 
and excessive fear or reluctance about 
being alone or without 
major attachment 
figures 
at 
home or in other settings. Children with separation anxiety disorder may be unable to stay or 
go in a room 
by themselves and may display  clinging  behavior, staying close to or 
 shadowing  the parent 
around the house, or requiring someone to be with them 
when going to 
another room 
in the house (Criterion A5). They have persistent 
reluctance or refusal 
to go to 
sleep without 
being near a major attachment 
figure or to sleep away from 
home (Criterion A6). 
Children with this disorder often have difficulty at 
bedtime and may insist 
that 
someone stay 
with them 
until 
they fall 
asleep. During the night, they may make their way to their parents  bed 
(or that 
of a significant 
other, such as a sibling). Children may be reluctant 
or refuse to attend 
camp, to sleep at 
friends  homes, or to go on errands. Adults may be uncomfortable when 
traveling independently (e.g., sleeping in a hotel 
room 
away from 
home or attachment 
figures). 
There may be repeated nightmares in which the content 
expresses the individual s separation 
anxiety (e.g., destruction of the family through fire, murder, or other catastrophe) (Criterion A7). 
Physical 
symptoms (e.g., headaches, abdominal 
complaints, nausea, vomiting) are common in 
children when separation from 
major attachment 
figures occurs or is anticipated (Criterion A8). 
Cardiovascular symptoms such as palpitations, dizziness, and feeling faint 
are rare in younger 
children but may occur in adolescents and adults. 


The disturbance must 
last 
for a period of at 
least 
4 weeks in children and adolescents younger 
than 18 years and is typically 6 months or longer in adults (Criterion B). However, the duration 
criterion for adults should be used as a general 
guide, with allowance for some degree of 



flexibility. The disturbance must 
cause clinically significant 
distress or impairment 
in social, 
academic, occupational, or other important areas of functioning (Criterion C). 


Associated Features 


When separated from 
major attachment 
figures, children and adults with separation anxiety 
disorder may exhibit 
social 
withdrawal, apathy, sadness, or difficulty concentrating on work or 
play. Depending on their age, individuals may have fears of animals, monsters, the dark, 
muggers, burglars, kidnappers, car accidents, plane travel, and other situations that 
are perceived 
as presenting danger to the family or themselves. Some individuals become homesick and 
extremely uncomfortable when away from 
home. Separation anxiety disorder in children may 
lead to school 
refusal, which in turn may lead to academic difficulties and social 
isolation. When 
extremely upset 
at 
the prospect 
of separation, children may show anger or occasionally 
aggression toward someone who is forcing separation. When alone, especially in the evening or 
the dark, young children may report 
unusual 
perceptual 
experiences (e.g., seeing people peering 
into their room, frightening creatures reaching for them, feeling eyes staring at 
them). Children 
with this disorder may be described as demanding, intrusive, and in need of constant 
attention, 
and, as adults, may appear dependent 
and overprotective as parents. Adults with the disorder are 
likely to text 
or phone their major attachment 
figures throughout 
the day and repeatedly check on 
their whereabouts. The individual s excessive demands often become a source of frustration for 
family members, leading to resentment and conflict within the family. 


Prevalence 


The 6-to 12-month prevalence of separation anxiety disorder in children is estimated to be 
approximately 4%. In a community sample of toddlers, separation anxiety disorder appears to be 
equally represented among girls and boys; 
however, school-age girls appear to have higher 
prevalence rates than school-age boys. In adolescents in the United States, the 12-month 
prevalence is 1.6%. Separation anxiety disorder decreases in prevalence from 
childhood through 
adolescence and adulthood. In clinical 
samples of children, the disorder is equally common in 
boys and girls in contrast to community samples, where the 


219 


disorder is more frequent 
in girls. Reports from 
children tend to yield higher rates of separation 
anxiety disorder than parent reports of the child s symptoms. 


For adults, the 12-month prevalence of separation anxiety disorder in the United States 
ranges from 
0.9% to 1.9%. Among adults with separation anxiety disorder, women tend to have 
higher prevalence rates of the disorder in both clinical 
and community studies. Across 18 
countries, the mean 12-month prevalence in adults is 1.0%, with a range of < 0.1% to 2.7% (e.g., 
0.3% in Romania, 2.7% in Colombia). A higher prevalence was observed in women compared 
with men in this total sample (1.3% compared with 0.8%). 


Development and Course 


Periods of heightened separation anxiety from 
attachment 
figures are part 
of normal 
early 
development 
and may indicate the development 
of secure attachment 
relationships (e.g., around 



age 1 year, when infants may experience stranger anxiety). Onset 
of separation anxiety disorder 
may be as early as preschool 
age and may occur at 
any time during childhood and in 
adolescence. Across 18 countries, median age at 
onset 
reported by adults (age 18 years and 
older) with the disorder is in late adolescence in high- and upper-middle-income countries and in 
the mid-20 s in low- and lower-middle-income countries. Most 
adults report 
a fluctuating course 
of the disorder over their lifetime, and they may report some symptoms in childhood. 


Typically there are periods of exacerbation and remission. In some cases, both the anxiety 
about 
possible separation and the avoidance of situations involving separation from 
the home or 
nuclear family (e.g., going away to college, moving away from 
attachment 
figures) may persist 
through adulthood. However, the majority of children with separation anxiety disorder are free of 
impairing anxiety disorders over their lifetimes. 


The manifestations of separation anxiety disorder vary with age. Younger children are more 
reluctant 
to go to school 
or may avoid school 
altogether. Younger children may not 
express 
worries or specific fears of definite threats to parents, home, or themselves, and the anxiety is 
manifested only when separation is experienced. As children age, worries emerge; these are often 
worries about 
specific dangers (e.g., accidents, kidnapping, mugging, death) or vague concerns 
about 
not 
being reunited with attachment 
figures. In adults, separation anxiety disorder may limit 
their ability to cope with changes in circumstances (e.g., moving, getting married). Adults with 
the disorder are typically overconcerned about 
their offspring, spouses, parents, and pets and 
experience marked discomfort 
when separated from 
them. They may also experience significant 
disruption in work or social 
experiences because of needing to continuously check on the 
whereabouts of a significant other. 


Risk and Prognostic Factors 


Environmental. 
Separation anxiety disorder often develops after life stress, especially a loss (e.g., 
the death of a relative or pet; 
an illness of the individual 
or a relative; 
a change of schools; 
parental 
divorce; 
a move to a new neighborhood; 
immigration; 
a disaster that 
involved periods of 
separation from 
attachment 
figures). Being bullied during childhood has been shown to be a risk 
factor for the development 
of separation anxiety disorder. In young adults, other examples of life 
stress include leaving the parental 
home, entering into a romantic relationship, and becoming a 
parent. A history of parental 
overprotection and intrusiveness may be associated with separation 
anxiety disorder in both childhood and adulthood. 


Genetic 
and 
physiological. 
There is evidence that 
separation anxiety disorder may be heritable. 
Heritability was estimated at 
73% in a community sample of 6-year-old twins, with higher rates 
found in girls. Children with separation anxiety disorder display particularly enhanced sensitivity 
to respiratory stimulation using CO2-enriched air. Separation anxiety disorder also appears to 


aggregate in families. 


220 


Culture-Related Diagnostic Issues 


There are cultural 
variations in the degree to which it 
is considered desirable to tolerate 
separation, so that 
demands and opportunities for separation between parents and children are 
avoided in some cultural 
contexts. For example, there is wide variation across countries and 



cultural 
contexts with respect 
to the age at 
which it 
is expected that 
offspring should leave the 
parental 
home. Youth vary in their self-reports of separation anxiety symptoms; 
for instance, 
Taiwanese youth endorse higher symptoms of separation anxiety compared with U.S. youth. It 
is 
important 
to differentiate separation anxiety disorder from 
the high value some cultural 
communities place on strong interdependence among family members. 


Association With Suicidal 
Thoughts or Behavior 


Separation anxiety disorder in children and adolescents may be associated with an increased risk 
for suicide, although this association is not 
specific to separation anxiety disorder and is found in 
other anxiety disorders where there is significant 
comorbidity. A large twin study showed that 
being bullied during childhood was a risk factor for suicidal thoughts during young adulthood. 


Functional 
Consequences of Separation Anxiety Disorder 


Individuals with separation anxiety disorder often limit 
independent 
activities away from 
home 
or attachment 
figures (e.g., in children, avoiding school, not 
going to camp, having difficulty 
sleeping alone; 
in adolescents, not 
going away to college; 
in adults, not 
leaving the parental 
home, not 
traveling long distances without 
their close attachments, not 
working outside the 
home). Symptoms in adults are often debilitating and affect 
multiple areas of their lives. For 
example, adults with separation anxiety disorder may deliberately reorganize their work 
schedules and other activities because of their anxieties about 
possible separations from 
close 
attachment 
figures; 
they may often express frustration with the limitations on their lives because 
of their need to maintain proximity to, or at 
least 
virtual 
contact 
with, their key attachment 
figures (e.g., by texting or phoning them 
repeatedly throughout 
the day). Separation anxiety 
disorder is associated with greater reported impairment 
in individuals from 
high- and upper-
middle-income countries compared with those from low- and lower-middle-income countries. 


Differential 
Diagnosis 


Generalized 
anxiety 
disorder. 
Separation anxiety disorder is distinguished from 
generalized anxiety 
disorder in that 
the anxiety in separation anxiety disorder predominantly concerns real 
or 
imagined separation from 
attachment 
figures. Furthermore, if other worries occur, they are not 
excessive. 


Panic 
disorder. 
In separation anxiety disorder, threats of separation from 
close attachments may 
lead to extreme anxiety and panic attacks. In contrast 
to panic disorder, where panic attacks 
occur unexpectedly and are usually accompanied by fears of dying or going  crazy,  the panic 
attacks in separation anxiety disorder occur in anticipation of real 
or imagined separations from 
attachment 
figures or places of safety and security, or from 
worries that 
untoward events will 
befall the individual s close attachments. 


Agoraphobia. 
Unlike individuals with agoraphobia, those with separation anxiety disorder are not 
anxious about 
being trapped or incapacitated in situations from 
which escape is perceived as 
difficult 
in the event 
of panic-like symptoms or other incapacitating symptoms. Instead, they fear 
being away from places of safety associated with their major attachment figures. 


221 



Conduct 
disorder. 
School 
avoidance (truancy) is common in conduct 
disorder, but 
anxiety about 
separation is not 
responsible for school 
absences, and the child or adolescent 
usually stays away 
from, rather than returns to, the home. 


Social 
anxiety 
disorder. 
School 
refusal 
may be attributable to social 
anxiety disorder. In such 
instances, the school 
avoidance is due to fear of being judged negatively by others rather than 
due to worries about being separated from attachment figures. 


Posttraumatic 
stress 
disorder. 
Fear of separation from 
loved ones is common after a traumatic 
event 
such as a major disaster, particularly when periods of separation from 
loved ones are 
experienced during the traumatic event. In posttraumatic stress disorder (PTSD), the central 
symptoms concern intrusions about, and avoidance of, memories associated with the traumatic 
event 
itself, whereas in separation anxiety disorder, the worries and avoidance concern the wellbeing 
of attachment figures and separation from them. 


Illness 
anxiety 
disorder. 
Separation anxiety disorder concerns worries about 
the health and wellbeing 
of close attachments. In contrast, individuals with illness anxiety disorder worry about 
specific medical 
illnesses they themselves may have, not 
about 
them 
being separated from 
their 
close attachments. 


Prolonged 
grief 
disorder. 
Intense yearning or longing for the deceased, intense sorrow and 
emotional 
pain, and preoccupation with the deceased or the circumstances of the death are 
expected responses occurring in prolonged grief disorder, whereas fear of possible separation 
from key attachment figures is central in separation anxiety disorder. 


Depressive 
and 
bipolar disorders. 
These disorders may be associated with reluctance to leave 
home, but 
the main concern is not 
worry or fear of untoward events befalling attachment 
figures, 
but 
rather low motivation for engaging with the outside world. However, individuals with 
separation anxiety disorder may become depressed while being separated or in anticipation of 
separation. 


Oppositional 
defiant 
disorder. 
Children and adolescents with separation anxiety disorder may be 
oppositional 
in the context 
of being forced to separate from 
attachment 
figures. Oppositional 
defiant 
disorder should be considered only when there is persistent 
oppositional 
behavior 
unrelated to the anticipation or occurrence of separation from attachment figures. 


Psychotic 
disorders. 
Unlike the hallucinations in psychotic disorders, the unusual 
perceptual 
experiences that 
may occur in separation anxiety disorder are usually based on a misperception 
of an actual 
stimulus, occur only in certain situations (e.g., nighttime), and are reversed by the 
presence of an attachment figure. 


Personality 
disorders. 
Dependent 
personality disorder is characterized by an indiscriminate 
tendency to rely on others, whereas separation anxiety disorder involves concern about 
the 
proximity and safety of key attachment 
figures. Borderline personality disorder is characterized 
by fear of abandonment 
by loved ones, but 
problems in identity, self-direction, interpersonal 
functioning, and impulsivity are additionally central 
to that 
disorder, whereas they are not 
central 
to separation anxiety disorder. 


Comorbidity 


In children, separation anxiety disorder is highly comorbid with generalized anxiety disorder and 



specific phobia. In adults, common comorbidities include specific phobia, PTSD, panic disorder, 
generalized anxiety disorder, social 
anxiety disorder, agoraphobia, obsessive-compulsive 
disorder, prolonged grief disorder, and personality disorders. Among the personality disorders, 
dependent, avoidant, and obsessive-compulsive (Cluster C) personality disorders may be 
comorbid with separation anxiety disorder. Depressive and bipolar disorders are also comorbid 
with separation anxiety disorder in adults. 


222 


Selective Mutism 


Diagnostic Criteria 
F94.0 


A. 
Consistent 
failure 
to 
speak in 
specific social situations in 
which 
there 
is an 
expectation 
for speaking 
(e.g., 
at 
school) despite 
speaking 
in 
other situations. 
B. 
The 
disturbance 
interferes with 
educational or occupational achievement 
or with 
social communication. 
C. 
The 
duration 
of 
the 
disturbance 
is at 
least 
1 
month 
(not 
limited 
to 
the 
first 
month 
of 
school). 
D. 
The 
failure 
to 
speak is not 
attributable 
to 
a 
lack of 
knowledge 
of, 
or comfort 
with, 
the 
spoken 
language 
required 
in 
the 
social situation. 
E. 
The 
disturbance 
is not 
better explained 
by a 
communication 
disorder (e.g., 
childhood-onset 
fluency disorder) and 
does not 
occur exclusively during 
the 
course 
of 
autism spectrum disorder, 
schizophrenia, 
or another psychotic 
disorder. 
Diagnostic Features 


When encountering other individuals in social 
interactions, children with selective mutism 
do not 
initiate speech or reciprocally respond when spoken to by others. Lack of speech occurs in social 
interactions with children or adults. Children with selective mutism 
will 
speak in their home in 
the presence of immediate family members but 
often not 
even in front 
of close friends or second-
degree relatives, such as grandparents or cousins. The disturbance is most 
often marked by high 
social 
anxiety. Children with selective mutism 
often refuse to speak at 
school, leading to 
academic or educational 
impairment, as teachers often find it 
difficult 
to assess skills such as 
reading. The lack of speech may interfere with social 
communication, although children with this 
disorder sometimes use nonspoken or nonverbal 
means (e.g., grunting, pointing, writing) to 
communicate and may be willing or eager to perform 
or engage in social 
encounters when 
speech is not required (e.g., nonverbal parts in school plays). 


Associated Features 


Associated features of selective mutism 
may include excessive shyness, fear of social 



embarrassment, social 
isolation and withdrawal, clinging, compulsive traits, negativism, temper 
tantrums, or mild oppositional 
behavior. Although children with this disorder generally have 
normal 
language skills, there may occasionally be an associated communication disorder, 
although no particular association with a specific communication disorder has been identified. 
Even when these disorders are present, anxiety is present 
as well. In clinical 
settings, children 
with selective mutism 
are almost 
always given an additional 
diagnosis of another anxiety 
disorder most commonly, social anxiety disorder. 


Prevalence 


Selective mutism 
is a relatively rare disorder and has not 
been included as a diagnostic category 
in epidemiological 
studies of prevalence of childhood disorders. Point 
prevalence using various 
clinic or school 
samples in the United States, Europe, and Israel 
ranges between 0.03% and 1.9% 
depending on the setting and ages of the sample. Studies in community-based and treatment-
seeking samples suggest 
an equal 
gender distribution for selective mutism, although there is also 
evidence that 
selective mutism 
is more common among girls than boys. Prevalence does not 
seem 
to vary by race/ethnicity, but 
individuals who need to speak in a non-native language (e.g., 
children of immigrant 
families) run greater risk for developing the disorder. The disorder is more 
likely to manifest in young children than in adolescents and adults. 


223 


Development and Course 


The onset 
of selective mutism 
is usually before age 5 years, but 
the disturbance may not 
come to 
clinical 
attention until 
entry into school, where there is an increase in social 
interaction and 
performance tasks, such as reading aloud. The persistence of the disorder is variable. Although 
clinical 
reports suggest 
that 
many individuals  outgrow  selective mutism, the longitudinal 
course of the disorder is largely unknown. In most 
cases, selective mutism 
may fade, but 
symptoms of social anxiety disorder often remain. 


Risk and Prognostic Factors 


Temperamental. 
Temperamental 
risk factors for selective mutism 
are not 
well 
identified. 
Negative affectivity (neuroticism) or behavioral 
inhibition may play a role, as may parental 
history of shyness, social 
isolation, and social 
anxiety. Children with selective mutism 
may have 
subtle receptive language difficulties compared with their peers, although receptive language is 
still within the normal range. 


Environmental. 
Social 
inhibition on the part 
of parents may serve as a model 
for social 
reticence 
and selective mutism 
in children. Furthermore, parents of children with selective mutism 
have 
been described as overprotective or more controlling than parents of children with other anxiety 
disorders or no disorder. 


Genetic 
and 
physiological. 
Because of the significant 
overlap between selective mutism 
and social 
anxiety disorder, there may be shared genetic factors between these conditions. There is also 
evidence for increased abnormalities in the auditory efferent 
neural 
activity during vocalization 
in individuals with selective mutism, which could lead to peculiarities in the perception of their 



own voice and hence a reticence to speak. 


Culture-Related Diagnostic Issues 


Children in families who have migrated to a country where a different 
language is spoken may 
appear to have selective mutism 
because they may refuse to speak the new language because of 
lack of knowledge of the language. Such children would not 
qualify for the diagnosis because 
such cases are explicitly excluded from the diagnosis. 


Functional 
Consequences of Selective Mutism 


Selective mutism 
may result 
in social 
impairment, as children may be too anxious to engage in 
reciprocal 
social 
interaction with other children. As children with selective mutism 
mature, they 
may face increasing social 
isolation. In school 
settings, these children may suffer academic 
impairment, because often they do not 
communicate with teachers regarding their academic or 
personal 
needs (e.g., not 
understanding a class assignment, not 
asking to use the restroom). 
Severe impairment 
in school 
and social 
functioning, including that 
resulting from 
teasing by 
peers, is common. In certain instances, selective mutism 
may serve as a compensatory strategy to 
decrease anxious arousal in social encounters. 


Differential 
Diagnosis 


Silent 
period 
in 
immigrant 
children 
learning 
a 
second 
language. 


Selective mutism 
must 
be 
distinguished from 
the typical 
 silent 
period  associated with the acquisition of a new language 
in young children. If comprehension of the new language is adequate but 
refusal 
to speak persists 
in both languages, in several 
unfamiliar settings, and for a prolonged period, a diagnosis of 
selective mutism may be warranted. 


Communication 
disorders. 
Selective mutism 
should be distinguished from 
speech disturbances 
that 
are better explained by a communication disorder, such as language disorder, speech sound 
disorder (previously phonological disorder), childhood-onset 


224 


fluency disorder (stuttering), or social 
(pragmatic) communication disorder. Unlike selective 
mutism, the speech disturbance in these conditions is not restricted to a specific social situation. 


Neurodevelopmental 
disorders 
and 
schizophrenia 
and 
other psychotic 
disorders. 


Individuals with an 
autism 
spectrum 
disorder, schizophrenia or another psychotic disorder, or severe intellectual 
developmental 
disorder (intellectual 
disability) may have problems in social 
communication and 
be unable to speak appropriately in social 
situations. In contrast, selective mutism 
should be 
diagnosed only when a child has an established capacity to speak in some social 
situations (e.g., 
typically at home). 


Social 
anxiety 
disorder. 
The social 
anxiety and social 
avoidance in social 
anxiety disorder may be 
associated with selective mutism. In such cases, both diagnoses may be given. 


Comorbidity 


The most 
common comorbid conditions are other anxiety disorders, most 
often social 
anxiety 



disorder, followed by separation anxiety disorder and specific phobia. In clinical 
settings, 
selective mutism 
and autism 
spectrum 
disorder have also been noted as frequently co-occurring 
conditions. Oppositional 
behaviors can be observed in a substantial 
minority of children with 
selective mutism, although this oppositional 
behavior may be limited to situations requiring 
speech. Communication delays or disorders also may appear in some children with selective 
mutism. 


Specific Phobia 


Diagnostic Criteria 


A. 
Marked 
fear or anxiety about 
a 
specific object 
or situation 
(e.g., 
flying, 
heights, 
animals, 
receiving 
an 
injection, 
seeing 
blood). 
Note: 
In 
children, 
the 
fear or anxiety may be 
expressed 
by crying, 
tantrums, 
freezing, 
or clinging. 


B. 
The 
phobic object 
or situation 
almost 
always provokes immediate 
fear or anxiety. 
C. 
The 
phobic object 
or situation 
is actively avoided 
or endured 
with 
intense 
fear or 
anxiety. 
D. 
The 
fear or anxiety is out 
of 
proportion 
to 
the 
actual danger posed 
by the 
specific 
object 
or situation 
and 
to 
the 
sociocultural context. 
E. 
The 
fear, 
anxiety, 
or avoidance 
is persistent, 
typically lasting 
for 6 
months or 
more. 
F. 
The 
fear, 
anxiety, 
or avoidance 
causes clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
G. 
The 
disturbance 
is not 
better explained 
by the 
symptoms of 
another mental 
disorder, 
including 
fear, 
anxiety, 
and 
avoidance 
of 
situations associated 
with 
panic-like 
symptoms or other incapacitating 
symptoms (as in 
agoraphobia); 
objects or situations related 
to 
obsessions (as in 
obsessive-compulsive 
disorder); 
reminders of 
traumatic events (as in 
posttraumatic stress disorder); 
separation 
from home 
or attachment 
figures (as in 
separation 
anxiety disorder); 
or social situations (as in 
social anxiety disorder). 
Specify 
if: 
Code 
based 
on 
the 
phobic stimulus: 
F40.218 
Animal 
(e.g., 
spiders, 
insects, 
dogs). 
F40.228 
Natural 
environment 
(e.g., 
heights, 
storms, 
water). 
F40.23x 
Blood-injection-injury 
(e.g., 
needles, 
invasive 
medical procedures). 


225 


Coding 
note: 
Select 
specific ICD-10-CM code 
as follows: 
F40.230 
fear of 
blood; 
F40.231 
fear of 
injections and 
transfusions; 
F40.232 
fear of 
other 



medical care; 
or F40.233 
fear of 
injury. 
F40.248 
Situational 
(e.g., 
airplanes, 
elevators, 
enclosed 
places). 
F40.298 
Other 
(e.g., 
situations that 
may lead 
to 
choking 
or vomiting; 
in 
children, 


e.g., 
loud 
sounds or costumed 
characters). 
Coding 
note: 
When 
more 
than 
one 
phobic stimulus is present, 
code 
all ICD-10-CM 
codes that 
apply (e.g., 
for fear of 
snakes and 
flying, 
F40.218 
specific phobia, 
animal, 
and 
F40.248 
specific phobia, 
situational). 


Specifiers 


It 
is common for individuals to have multiple specific phobias. The average individual 
with 
specific phobia fears three objects or situations, and approximately 75% of individuals with 
specific phobia fear more than one situation or object. In such cases, multiple specific phobia 
diagnoses, each with its own diagnostic code reflecting the phobic stimulus, would need to be 
given. For example, if an individual fears thunderstorms and flying, then two diagnoses would be 
given: specific phobia, natural environment, and specific phobia, situational. 


Diagnostic Features 


A key feature of this disorder is that 
the fear or anxiety is circumscribed to the presence of a 
particular situation or object 
(Criterion A), which may be termed the phobic stimulus. 
The 
categories of feared situations or objects are provided as specifiers. Many individuals fear objects 
or situations from 
more than one category, or phobic stimulus. For the diagnosis of specific 
phobia, the response must 
differ from 
normal, transient 
fears that 
commonly occur in the 
population. To meet the criteria for a diagnosis, the fear or anxiety must be intense or severe (i.e., 
 marked ) (Criterion A). The amount 
of fear experienced may vary with proximity to the feared 
object 
or situation and may occur in anticipation of or in the actual 
presence of the object 
or 
situation. Also, the fear or anxiety may take the form 
of a full 
or limited symptom 
panic attack 
(i.e., expected panic attack). Another characteristic of specific phobias is that 
fear or anxiety is 
evoked nearly every time the individual 
comes into contact 
with the phobic stimulus (Criterion 
B). Thus, an individual 
who becomes anxious only occasionally upon being confronted with the 
situation or object 
(e.g., becomes anxious when flying only on one out 
of every five airplane 
flights) would not 
be diagnosed with specific phobia. However, the degree of fear or anxiety 
expressed may vary (from 
anticipatory anxiety to a full 
panic attack) across different 
occasions 
of encountering the phobic object 
or situation because of various contextual 
factors such as the 
presence of others, duration of exposure, and other threatening elements such as turbulence on a 
flight 
for individuals who fear flying. Fear and anxiety are often expressed differently between 
children and adults. Also, the fear or anxiety occurs as soon as the phobic object 
or situation is 
encountered (i.e., immediately rather than being delayed). 


The individual 
actively avoids the situation, or if he or she either is unable or decides not 
to 
avoid it, the situation or object 
evokes intense fear or anxiety (Criterion C). Active avoidance 
means the individual 
intentionally behaves in ways that 
are designed to prevent 
or minimize 
contact 
with phobic objects or situations (e.g., takes tunnels instead of bridges on daily commute 
to work for fear of heights; 
avoids entering a dark room 
for fear of spiders; 
avoids accepting a 
job in a locale where a phobic stimulus is more common). Avoidance behaviors are often 



obvious (e.g., an individual 
who fears blood refusing to go to the doctor) but 
are sometimes less 
obvious (e.g., an individual 
who fears snakes refusing to look at 
pictures that 
resemble the form 
or shape of snakes). Many individuals with specific phobias have suffered over many years and 
have changed their living circumstances in 


226 


ways designed to avoid the phobic object 
or situation as much as possible (e.g., an individual 
diagnosed with specific phobia, animal, who moves to reside in an area devoid of the particular 
feared animal). Therefore, they no longer experience fear or anxiety in their daily life. In such 
instances, avoidance behaviors or ongoing refusal 
to engage in activities that 
would involve 
exposure to the phobic object 
or situation (e.g., repeated refusal 
to accept 
offers for work-related 
travel 
because of fear of flying) may be helpful 
in confirming the diagnosis in the absence of 
overt anxiety or panic. 


The fear or anxiety is out 
of proportion to the actual 
danger that 
the object 
or situation poses, 
or more intense than is deemed necessary (Criterion D). Although individuals with specific 
phobia often recognize their reactions as disproportionate, they tend to overestimate the danger 
in their feared situations, and thus the judgment 
of being out 
of proportion is made by the 
clinician. The individual s sociocultural 
context 
should also be considered. For example, fears of 
the dark may be reasonable in a context 
of ongoing violence, and the degree of fear of insects 
considered to be disproportionate would be higher in settings where insects are consumed in the 
diet. The fear, anxiety, or avoidance is persistent, typically lasting for 6 months or more 
(Criterion E), which helps distinguish the disorder from 
transient 
fears that 
are common in the 
population, particularly among children. The specific phobia must 
cause clinically significant 
distress or impairment in social, occupational, or other important areas of functioning in order for 
the disorder to be diagnosed (Criterion F). 


Associated Features 


Individuals with specific phobia typically experience an increase in physiological 
arousal 
in 
anticipation of or during exposure to a phobic object 
or situation. However, the physiological 
response to the feared situation or object 
varies. Whereas individuals with situational, natural 
environment, and animal specific phobias are likely to show sympathetic nervous system arousal, 
individuals with blood-injection-injury specific phobia often demonstrate a vasovagal 
fainting or 
near-fainting response that 
is marked by initial 
brief acceleration of heart 
rate and elevation of 
blood pressure followed by a deceleration of heart 
rate and a drop in blood pressure. 
Additionally, specific phobia is most 
consistently associated with abnormal 
activity in the 
amygdala, anterior cingulate cortex, thalamus, and insula in response to the phobic 
object/situation. 


Prevalence 


In the United States, the 12-month community prevalence estimate for specific phobia is 
approximately 8% 12%. Prevalence rates in European countries are largely similar to those in 
the United States (e.g., about 
6%), but 
rates are generally lower in Asian, African, and Latin 
American countries (2% 4%). Prevalence estimates in children average approximately 5% 



across various countries, with a range of 3% 9%, and are approximately 16% in adolescents ages 
13 17 years in the United States. Prevalence estimates are lower in older individuals (about 
3%  
5%), possibly reflecting diminishing severity to subclinical 
levels. Women are more frequently 
affected than men across subtypes, at a rate of approximately 2:1. 


Development and Course 


Specific phobia sometimes develops following a traumatic event 
(e.g., being attacked by an 
animal 
or stuck in an elevator), observation of others going through a traumatic event 
(e.g., 
watching someone drown), an unexpected panic attack in the to be feared situation (e.g., an 
unexpected panic attack while on the subway), or informational 
transmission (e.g., extensive 
media coverage of a plane crash). However, many individuals with specific phobia are unable to 
recall 
the specific reason for the onset 
of their phobias. Specific phobia usually develops in early 
childhood, with the majority of cases developing prior to age 10 years. Median age at 
onset 
is 
between 7 and 11 years, with the mean at about 10 years. 


227 


Situational 
specific phobias tend to have a later age at 
onset 
than natural 
environment, animal, or 
blood-injection-injury specific phobias. Specific phobias that 
develop in childhood and 
adolescence are likely to wax and wane during that 
period. However, phobias that 
do persist 
into 
adulthood are unlikely to remit for the majority of individuals. 


When specific phobia is being diagnosed in children, two issues should be considered. First, 
young children may express their fear and anxiety by crying, tantrums, freezing, or clinging. 
Second, young children typically are not 
able to understand the concept 
of avoidance. Therefore, 
the clinician should assemble additional 
information from 
parents, teachers, or others who know 
the child well. Excessive fears are quite common in young children but 
are usually transitory and 
only mildly impairing and thus considered developmentally appropriate. In such cases a 
diagnosis of specific phobia would not 
be made. When the diagnosis of specific phobia is being 
considered in a child, it 
is important 
to assess the degree of impairment 
and the duration of the 
fear, anxiety, or avoidance, and whether it 
is typical 
for the child s particular developmental 
stage. 


Although the prevalence of specific phobia is lower in older populations, it 
remains one of 
the more commonly experienced disorders in late life. Several 
issues should be considered when 
diagnosing specific phobia in older populations. First, older individuals may be more likely to 
endorse natural 
environment 
specific phobias, as well 
as phobias of falling. Second, specific 
phobia (like all 
anxiety disorders) tends to co-occur with medical 
concerns in older individuals, 
including coronary heart 
disease, chronic obstructive pulmonary disease, and Parkinson s 
disease. Third, older individuals may be more likely to attribute the symptoms of anxiety to 
medical 
conditions. Fourth, older individuals may be more likely to manifest 
anxiety in an 
atypical 
manner (e.g., involving symptoms of both anxiety and depression) and thus be more 
likely to warrant 
a diagnosis of unspecified anxiety disorder. Additionally, the presence of 
specific phobia in older adults is associated with decreased quality of life and may serve as a risk 
factor for major neurocognitive disorder. 


Although most 
specific phobias develop in childhood and adolescence, it 
is possible for a 



specific phobia to develop at 
any age, often as the result 
of experiences that 
are traumatic. For 
example, phobias of choking almost always follow a near-choking event at any age. 


Risk and Prognostic Factors 


Temperamental. 
Temperamental 
risk factors for specific phobia, such as negative affectivity 


(neuroticism) or behavioral inhibition, are risk factors for other anxiety disorders as well. 
Environmental. 
Environmental 
risk factors for specific phobias, such as parental 
overprotectiveness, parental 
loss and separation, and physical 
and sexual 
abuse, tend to predict 
other anxiety disorders as well. As noted earlier, negative or traumatic encounters with the feared 
object or situation sometimes (but not always) precede the development of specific phobia. 


Genetic 
and 
physiological. 
There may be a genetic susceptibility to a certain category of specific 
phobia (e.g., an individual 
with a first-degree relative with a specific phobia of animals is 
significantly more likely to have the same type of specific phobia than any other category of 
phobia). Twin studies have examined the heritability of individual 
subtypes of fears and phobias, 
suggesting that 
animal 
phobia has approximately 32% heritability, blood-injury-injection phobia 
has 33%, and situational phobia has 25%. 


Culture-Related Diagnostic Issues 


In the United States, individuals of Asian and Latinx descent 
report 
lower prevalence of specific 
phobia than non-Latinx Whites and African Americans. The prevalence of specific phobia 
subtypes varies cross-nationally. 


228 


Sex- and Gender-Related Diagnostic Issues 


Animal, natural 
environment, and situational 
specific phobias are predominantly experienced by 
women, whereas blood-injection-injury phobia is experienced nearly equally among women and 
men. The average age at 
onset 
of specific phobia during childhood does not 
differ between 
girls/women and boys/men. 


Association With Suicidal 
Thoughts or Behavior 


Specific phobia is associated with both suicidal 
thoughts and suicide attempts based on national 


U.S. survey data. Specific phobia is also associated with a transition from 
ideation to attempt. 
For individuals in the community ages 14 24 years, a large prospective study over a 10-year 
period in Germany found that 
30% of first 
suicide attempts could be attributable to specific 
phobia. 
Functional 
Consequences of Specific Phobia 


Individuals with specific phobia show similar patterns of impairment 
in psychosocial 
functioning 
and decreased quality of life as individuals with other anxiety disorders and alcohol 
and 
substance use disorders, including impairments in occupational 
and interpersonal 
functioning. In 
older adults, impairment 
may be seen in caregiving duties and volunteer activities. Also, fear of 



falling in older adults can lead to reduced mobility and reduced physical 
and social 
functioning, 
and may lead to receiving formal 
or informal 
home support. The distress and impairment 
caused 
by specific phobias tend to increase with the number of feared objects and situations. Thus, an 
individual 
who fears four objects or situations is likely to have more impairment 
in his or her 
occupational 
and social 
roles and a lower quality of life than an individual 
who fears only one 
object 
or situation. Individuals with blood-injection-injury specific phobia are often reluctant 
to 
obtain medical 
care even when a medical 
concern is present. Additionally, fear of vomiting and 
choking may substantially reduce dietary intake. 


Differential 
Diagnosis 


Agoraphobia. 
Situational 
specific phobia may resemble agoraphobia in its clinical 
presentation, 
given the overlap in feared situations (e.g., flying, enclosed places, elevators). If an individual 
fears only one of the agoraphobic situations, then specific phobia, situational, may be diagnosed. 
If two or more agoraphobic situations are feared, a diagnosis of agoraphobia is likely warranted. 
For example, an individual 
who fears airplanes and elevators (which overlap with the  public 
transportation  agoraphobic situation) but 
does not 
fear other agoraphobic situations would be 
diagnosed with specific phobia, situational, whereas an individual 
who fears airplanes, elevators, 
and crowds (which overlap with two agoraphobic situations,  using public transportation  and 
 standing in line or being in a crowd ) would be diagnosed with agoraphobia. Criterion B 
of 
agoraphobia (the situations are feared or avoided  because of thoughts that 
escape might 
be 
difficult 
or help might 
not 
be available in the event 
of developing panic-like symptoms or other 
incapacitating or embarrassing symptoms ) can also be useful 
in differentiating agoraphobia 
from 
specific phobia. If the situations are feared for reasons other than not 
being able to escape 
or get 
help, such as fear of being harmed directly by the object 
or situation (e.g., fear of the plane 
crashing, fear of the animal biting), a specific phobia diagnosis may be more appropriate. 


Social 
anxiety 
disorder. 
If the situations are feared because of negative evaluation, social 
anxiety 


disorder should be diagnosed instead of specific phobia. 
Separation 
anxiety 
disorder. 
If the situations are feared because of separation from 
a primary 
caregiver or attachment 
figure, separation anxiety disorder should be diagnosed instead of 
specific phobia. 


229 


Panic 
disorder. 
Individuals with specific phobia may experience panic attacks when confronted 
with their feared situation or object. A diagnosis of specific phobia would be given if the panic 
attacks only occurred in response to the specific object 
or situation, whereas a diagnosis of panic 
disorder would be given if the individual 
also experienced panic attacks that 
were unexpected 
(i.e., not in response to the specific phobia object or situation). 


Obsessive-compulsive 
disorder. 
If an individual s primary fear or anxiety is of an object 
or 
situation as a result 
of obsessions (e.g., fear of blood due to obsessive thoughts about 
contamination from 
blood-borne pathogens [i.e., HIV]; 
fear of driving due to obsessive images 
of harming others), and if other diagnostic criteria for obsessive-compulsive disorder are met, 
then obsessive-compulsive disorder should be diagnosed. 



Trauma-and 
stressor-related 
disorders. 
If the phobia develops following a traumatic event, 
posttraumatic stress disorder (PTSD) should be considered as a diagnosis. However, traumatic 
events can precede the onset 
of PTSD and specific phobia. In this case, a diagnosis of specific 
phobia would be assigned only if all of the criteria for PTSD are not met. 


Eating 
disorders. 
A diagnosis of specific phobia is not 
given if the avoidance behavior is 
exclusively limited to avoidance of food and food-related cues, in which case a diagnosis of 
anorexia nervosa or bulimia nervosa should be considered. 


Schizophrenia 
spectrum and 
other psychotic 
disorders. 


When the fear and avoidance are attributable 
to delusional 
thinking (as in schizophrenia or other schizophrenia spectrum 
and other psychotic 
disorders), a diagnosis of specific phobia is not warranted. 


Comorbidity 


Specific phobia is rarely seen in medical-clinical 
settings in the absence of other 
psychopathology and is more frequently seen in nonmedical 
mental 
health settings. Specific 
phobia is frequently associated with a range of other disorders. Because of early onset, specific 
phobia is typically the temporally primary disorder. Individuals with specific phobia are at 
increased risk for the development 
of other disorders, including other anxiety disorders, 
depressive and bipolar disorders, substance-related disorders, somatic symptom 
and related 
disorders, and personality disorders (particularly dependent personality disorder). 


Social 
Anxiety Disorder 


Diagnostic Criteria 
F40.10 


A. 
Marked 
fear or anxiety about 
one 
or more 
social situations in 
which 
the 
individual 
is exposed 
to 
possible 
scrutiny by others. 
Examples include 
social interactions 
(e.g., 
having 
a 
conversation, 
meeting 
unfamiliar people), 
being 
observed 
(e.g., 
eating 
or drinking), 
and 
performing 
in 
front 
of 
others (e.g., 
giving 
a 
speech). 
Note: 
In 
children, 
the 
anxiety must 
occur in 
peer settings and 
not 
just 
during 
interactions with 
adults. 


B. 
The 
individual fears that 
he 
or she 
will act 
in 
a 
way or show anxiety symptoms 
that 
will be 
negatively evaluated 
(i.e., 
will be 
humiliating 
or embarrassing; 
will 
lead 
to 
rejection 
or offend 
others). 
C. 
The 
social situations almost 
always provoke 
fear or anxiety. 
Note: 
In 
children, 
the 
fear or anxiety may be 
expressed 
by crying, 
tantrums, 
freezing, 
clinging, 
shrinking, 
or failing 
to 
speak in 
social situations. 


D. 
The 
social situations are 
avoided 
or endured 
with 
intense 
fear or anxiety. 
E. 
The 
fear or anxiety is out 
of 
proportion 
to 
the 
actual threat 
posed 
by the 
social 
situation 
and 
to 
the 
sociocultural context. 
230 



F. 
The 
fear, 
anxiety, 
or avoidance 
is persistent, 
typically lasting 
for 6 
months or 
more. 
G. 
The 
fear, 
anxiety, 
or avoidance 
causes clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
H. 
The 
fear, 
anxiety, 
or avoidance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition. 
I. 
The 
fear, 
anxiety, 
or avoidance 
is not 
better explained 
by the 
symptoms of 
another mental disorder, 
such 
as panic disorder, 
body dysmorphic disorder, 
or 
autism spectrum disorder. 
J. 
If 
another medical condition 
(e.g., 
Parkinson s disease, 
obesity, 
disfigurement 
from burns or injury) is present, 
the 
fear, 
anxiety, 
or 
avoidance 
is clearly 
unrelated 
or is excessive. 
Specify 
if: 
Performance 
only: 
If 
the 
fear is restricted 
to 
speaking 
or performing 
in 
public. 


Specifiers 


Individuals with the performance only type of social 
anxiety disorder have performance fears 
that 
are typically most 
impairing in their professional 
lives (e.g., musicians, dancers, performers, 
athletes) or in roles that 
require regular public speaking. Performance fears may also manifest 
in 
work, school, or academic settings in which regular public presentations are required. Individuals 
with performance only social 
anxiety disorder do not 
fear or avoid nonperformance social 
situations. 


Diagnostic Features 


The essential 
feature of social 
anxiety disorder is a marked, or intense, fear or anxiety of social 
situations in which the individual 
may be scrutinized by others. In children the fear or anxiety 
must 
occur in peer settings and not 
just 
during interactions with adults (Criterion A). When 
exposed to such social 
situations, the individual 
fears that 
he or she will 
be negatively evaluated. 
The individual 
is concerned that 
he or she will 
be judged as anxious, weak, crazy, stupid, boring, 
intimidating, dirty, or unlikable. The individual 
fears that 
he or she will 
act 
or appear in a certain 
way or show anxiety symptoms, such as blushing, trembling, sweating, stumbling over one s 
words, or staring, that 
will 
be negatively evaluated by others (Criterion B). Some individuals fear 
offending others or being rejected as a result. Fear of offending others for example, by a gaze 
or by showing anxiety symptoms may be the predominant 
fear in individuals from 
cultures 
with strong collectivistic orientations. An individual 
with fear of trembling of the hands may 
avoid drinking, eating, writing, or pointing in public; 
an individual 
with fear of sweating may 
avoid shaking hands or eating spicy foods; 
and an individual 
with fear of blushing may avoid 
public performance, bright 
lights, or discussion about 
intimate topics. Some individuals fear and 
avoid urinating in public restrooms when other individuals are present 
(i.e., paruresis, or  shy 
bladder syndrome ). 


The social 
situations almost 
always provoke fear or anxiety (Criterion C). Thus, an individual 
who becomes anxious only occasionally in the social 
situation(s) would not 
be diagnosed with 



social 
anxiety disorder. However, the degree and type of fear and anxiety may vary (e.g., 
anticipatory anxiety, a panic attack) across different 
occasions. The anticipatory anxiety may 
occur sometimes far in advance of upcoming situations (e.g., worrying every day for weeks 
before attending a social 
event, repeating a speech for days in advance). In children, the fear or 
anxiety may be expressed by crying, tantrums, freezing, clinging, or shrinking in social 
situations. The individual 
will 
often avoid the feared social 
situations. Alternatively, the 
situations are endured with intense fear or anxiety (Criterion D). Avoidance can be extensive 
(e.g., not 
going to parties, refusing school) or subtle (e.g., overpreparing the text 
of a speech, 
diverting attention to others, limiting eye contact). 


The fear or anxiety is judged to be out 
of proportion to the actual 
risk of being negatively 
evaluated or to the consequences of such negative evaluation (Criterion E). 


231 


Sometimes, the anxiety may not 
be judged to be excessive, because it 
is related to an actual 
danger (e.g., being bullied or tormented by others). However, individuals with social 
anxiety 
disorder often overestimate the negative consequences of social 
situations, and thus the judgment 
of being out 
of proportion is made by the clinician. The individual s sociocultural 
context 
needs 
to be taken into account 
when this judgment 
is being made. For example, in certain cultures, 
behavior that 
might 
otherwise appear socially anxious may be considered appropriate in social 
situations (e.g., might be seen as a sign of respect). 


The duration of the disturbance is typically at 
least 
6 months (Criterion F). This duration 
threshold helps distinguish the disorder from 
transient 
social 
fears that 
are common, particularly 
among children and in the community. The fear, anxiety, and avoidance must 
interfere 
significantly with the individual s normal 
routine, occupational 
or academic functioning, or 
social 
activities or relationships, or must 
cause clinically significant 
distress (Criterion G). For 
example, an individual 
who is afraid to speak in public would not 
receive a diagnosis of social 
anxiety disorder if this activity is not 
routinely encountered on the job or in classroom 
work, and 
if the individual 
is not 
significantly distressed about 
it. However, if the individual 
avoids, or is 
passed over for, the job or education he or she really wants because of social 
anxiety symptoms, 
Criterion G is met. 


Associated Features 


Individuals with social 
anxiety disorder may be inadequately assertive or excessively submissive 
or, less commonly, highly controlling of the conversation. They may show overly rigid body 
posture or inadequate eye contact, or speak with an overly soft 
voice. These individuals may be 
shy or withdrawn, and they may be less open in conversations and disclose little about 
themselves. They may seek employment 
in jobs that 
do not 
require social 
contact, although this 
is not 
the case for individuals with social 
anxiety disorder, performance only. They may live at 
home longer. Men may be delayed in marrying and having a family, whereas women who would 
want 
to work outside the home may live a life without 
ever doing so. Self-medication with 
substances is common (e.g., drinking before going to a party). Social 
anxiety among older adults 
may also include exacerbation of symptoms of medical 
illnesses, such as increased tremor or 
tachycardia. Blushing is a hallmark physical response of social anxiety disorder. 



Prevalence 


The 12-month prevalence estimate of social 
anxiety disorder for the United States is 
approximately 7%. Lower 12-month prevalence estimates are seen in much of the world using 
the same diagnostic instrument, clustering around 0.5% 2.0%; 
median prevalence in Europe is 
2.3%. Prevalence appears to be increasing in the United States and East 
Asian countries. Twelvemonth 
prevalence rates in young adolescents (ages 13 17 years) are roughly half those in adults. 
Twelve-month prevalence rates decrease after age 65. The 12-month prevalence for older adults 
in North America, Europe, and Australia ranges from 
2% to 5%. In general, higher rates of social 
anxiety disorder are found in women than in men in the general 
population (with odds ratios 
ranging from 
1.5 to 2.2), and the gender difference in prevalence is more pronounced in 
adolescents and young adults. Gender rates are equivalent 
or slightly higher for men in clinical 
samples, and it 
is assumed that 
gender roles and social 
expectations play a significant 
role in 
explaining the heightened help-seeking behavior in men. Prevalence in the United States has 
been found to be lower in individuals of Asian, Latinx, African American, and Caribbean Black 
descent compared with non-Hispanic Whites. 


Development and Course 


Median age at 
onset 
of social 
anxiety disorder in the United States is 13 years, and 75% of 
individuals have an age at onset between 8 and 15 years. The disorder sometimes emerges 


232 


out 
of a childhood history of social 
inhibition or shyness in U.S. and European studies. Onset 
can 
also occur in early childhood. Onset 
of social 
anxiety disorder may follow a stressful 
or 
humiliating experience (e.g., being bullied, vomiting during a public speech), or it 
may be 
insidious, developing slowly. First 
onset 
in adulthood is relatively rare and is more likely to 
occur after a stressful 
or humiliating event 
or after life changes that 
require new social 
roles (e.g., 
marrying someone from 
a different 
social 
class, receiving a job promotion). Social 
anxiety 
disorder may diminish after an individual 
with fear of dating marries and may reemerge after 
divorce. Among individuals presenting to clinical 
care, the disorder tends to be particularly 
persistent. 


Adolescents endorse a broader pattern of fear and avoidance, including of dating, compared 
with younger children. Older adults express social 
anxiety at 
lower levels but 
across a broader 
range of situations, whereas younger adults express higher levels of social 
anxiety for specific 
situations. In older adults, social 
anxiety may concern disability due to declining sensory 
functioning (hearing, vision) or embarrassment 
about 
one s appearance (e.g., tremor as a 
symptom 
of Parkinson s disease) or functioning due to medical 
conditions, incontinence, or 
cognitive impairment 
(e.g., forgetting people s names). Detection of social 
anxiety disorder in 
older adults may be challenging because of several 
factors, including a focus on somatic 
symptoms, comorbid medical 
illness, limited insight, changes to social 
environment 
or roles that 
may obscure impairment 
in social 
functioning, or reticence about 
describing psychological 
distress. There is large variation in rates of remission for social 
anxiety disorder, suggestive of 
different trajectories (short, fluctuating, and chronic). 



Risk and Prognostic Factors 


Temperamental. 
Underlying traits that 
predispose individuals to social 
anxiety disorder include 
behavioral 
inhibition and fear of negative evaluation, as well 
as harm 
avoidance. Personality 
traits consistently associated with social 
anxiety disorder are high negative affectivity 
(neuroticism) and low extraversion. 


Environmental. 
There is evidence that negative social experiences, particularly peer victimization, 
are associated with the development 
of social 
anxiety disorder, although causal 
pathways remain 
unknown. Childhood maltreatment 
and adversity are risk factors for social 
anxiety disorder. 
Among African Americans and Caribbean Blacks in the United States, everyday forms of ethnic 
discrimination and racism are associated with social anxiety disorder. 


Genetic 
and 
physiological. 
Traits predisposing individuals to social 
anxiety disorder, such as 
behavioral 
inhibition, are strongly genetically influenced. The genetic influence is subject 
to 
gene-environment 
interaction; 
that 
is, children with high behavioral 
inhibition are more 
susceptible to environmental 
influences, such as socially anxious modeling by parents. Also, 
social 
anxiety disorder is heritable. First-degree relatives have a two to six times greater chance 
of having social 
anxiety disorder, and liability to the disorder involves the interplay of disorder-
specific (e.g., fear of negative evaluation) and nonspecific (e.g., negative affectivity 
[neuroticism]) genetic factors. Genetic contribution to social 
anxiety disorder has been found to 
be higher for social 
anxiety disorder in children than social 
anxiety disorder in adults and higher 
for social anxiety symptoms than a clinical diagnosis of social anxiety disorder. 


Culture-Related Diagnostic Issues 


The nature and types of social 
situations that 
precipitate symptoms of social 
anxiety disorder are 
similar across U.S. ethnoracial 
groups, including fear of performance/public speaking, social 
interaction, and being observed. U.S. non-Latinx Whites report 
an earlier age at 
onset 
of social 
anxiety disorder than U.S. Latinx, yet 
the latter describe greater impairment 
across home, work, 
and relationship domains associated with the disorder. 


233 


Immigrant 
status is associated with lower rates of social 
anxiety disorder in both Latinx and non-
Latinx White groups. The syndrome of taijin kyofusho 
(e.g., in Japan and Korea) is often 
characterized by social-evaluative concerns, fulfilling criteria for social 
anxiety disorder, which 
are associated with the fear that the individual makes other people uncomfortable (e.g.,  My gaze 
upsets people so they look away and avoid me ), a fear that 
is at 
times experienced with 
delusional 
intensity. Other presentations of taijin kyofusho 
may fulfill 
criteria for body 
dysmorphic disorder or delusional disorder. 


Sex- and Gender-Related Diagnostic Issues 


Age at 
onset 
of social 
anxiety disorder does not 
differ by gender. Women with social 
anxiety 
disorder report 
a greater number of social 
fears and comorbid major depressive disorder and 
other anxiety disorders, whereas men are more likely to fear dating; 
have oppositional 
defiant 
disorder, conduct 
disorder, or antisocial 
personality disorder; 
and use alcohol 
and illicit 
drugs to 



relieve symptoms of the disorder. Paruresis is more common in men. 


Association With Suicidal 
Thoughts or Behavior 


Among U.S. adolescents, social 
anxiety disorder has been reported to increase the risk for active 
suicidal 
thoughts and suicide attempts in Latinx but 
not 
in non-Latinx Whites, independently of 
the effect of major depression and family income. 


Functional 
Consequences of Social 
Anxiety Disorder 


Social 
anxiety disorder is associated with elevated rates of school 
dropout 
and with decreased 
well-being, employment, workplace productivity, socioeconomic status, and quality of life. 
Social 
anxiety disorder is also associated with being single, unmarried, or divorced and with not 
having children, particularly among men, whereas women are more likely to be unemployed. 
Social 
anxiety disorder is also negatively associated with friendship quality, such that 
individuals 
with social 
anxiety disorder report 
having friendships that 
are less close and less supportive than 
persons without 
the disorder. In older adults, there may be impairment 
in caregiving duties and 
volunteer activities. Social 
anxiety disorder also impedes leisure activities. Despite the extent 
of 
distress and social 
impairment 
associated with social 
anxiety disorder, only about 
half of 
individuals with the disorder in high-income societies ever seek treatment, and they tend to do so 
only after 15 20 years of experiencing symptoms. Not 
being employed is a strong predictor for 
the persistence of social anxiety disorder. 


Differential 
Diagnosis 


Normative 
shyness. 
Shyness (i.e., social 
reticence) is a common personality trait 
and is not 
by 
itself pathological. In some societies, shyness is even evaluated positively. However, when there 
is a significant 
adverse impact 
on social, occupational, and other important 
areas of functioning, 
a diagnosis of social 
anxiety disorder should be considered, and when full 
diagnostic criteria for 
social 
anxiety disorder are met, the disorder should be diagnosed. Only a minority (12%) of self-
identified shy individuals in the United States have symptoms that 
meet 
diagnostic criteria for 
social anxiety disorder. 


Agoraphobia. 
Individuals with agoraphobia may fear and avoid social 
situations (e.g., going to a 
movie) because escape might 
be difficult 
or help might 
not 
be available in the event 
of 
incapacitation or panic-like symptoms, whereas individuals with social 
anxiety disorder are most 
fearful 
of scrutiny by others. Moreover, individuals with social 
anxiety disorder are likely to be 
calm when left entirely alone, which is often not the case in agoraphobia. 


234 


Panic 
disorder. 
Individuals with social 
anxiety disorder may have panic attacks, but 
the panic 
attacks are always cued by social 
situations and do not 
occur  out 
of the blue.  Additionally, 
individuals with social 
anxiety disorder are more likely to be distressed by fear of negative 
evaluation stemming from a panic attack than by the panic attacks themselves. 


Generalized 
anxiety 
disorder. 
Social 
worries are common in generalized anxiety disorder, but 
the 
focus is more on the nature of ongoing relationships rather than on fear of negative evaluation. 



Individuals with generalized anxiety disorder, particularly children, may have excessive worries 
about 
the quality of their social 
performance, but 
these worries also pertain to nonsocial 
performance and when the individual 
is not 
being evaluated by others. In social 
anxiety disorder, 
the worries focus on social performance and others  evaluation. 


Separation 
anxiety 
disorder. 
Individuals with separation anxiety disorder may avoid social 
settings 
(including school 
refusal) because of concerns about 
being separated from 
attachment 
figures or, 
in children, about 
requiring the presence of a parent 
when it 
is not 
developmentally appropriate. 
Individuals with separation anxiety disorder are usually comfortable in social 
settings when their 
attachment 
figure is present 
or when they are at 
home, whereas those with social 
anxiety disorder 
may be uncomfortable when social 
situations occur at 
home or in the presence of attachment 
figures. 


Specific 
phobias. 
Individuals with specific phobias may fear embarrassment 
or humiliation (e.g., 
embarrassment 
about 
fainting when they have their blood drawn), but 
they do not 
generally fear 
negative evaluation in other social situations. 


Selective 
mutism. 
Individuals with selective mutism 
may fail 
to speak because of fear of negative 
evaluation, but 
they do not 
fear negative evaluation in social 
situations where no speaking is 
required (e.g., nonverbal play). 


Major depressive 
disorder. 
Individuals with major depressive disorder may be concerned about 
being negatively evaluated by others because they feel 
they are bad or not 
worthy of being liked. 
In contrast, individuals with social 
anxiety disorder are worried about 
being negatively evaluated 
because of certain social behaviors or physical symptoms. 


Body 
dysmorphic 
disorder. 
Individuals with body dysmorphic disorder are preoccupied with one 
or more perceived defects or flaws in their physical 
appearance that 
are not 
observable or appear 
slight 
to others; 
this preoccupation often causes social 
anxiety and avoidance. If their social 
fears 
and avoidance are caused only by their beliefs about 
their appearance, a separate diagnosis of 
social anxiety disorder is not warranted. 


Delusional 
disorder. 
Individuals with delusional 
disorder may have nonbizarre delusions and/or 
hallucinations related to the delusional 
theme that 
focus on being rejected by or offending others. 
Although extent 
of insight 
into beliefs about 
social 
situations may vary, many individuals with 
social 
anxiety disorder have good insight 
that 
their beliefs are out 
of proportion to the actual 
threat posed by the social situation. 


Autism spectrum disorder. 
Social 
anxiety and social 
communication deficits are hallmarks of 
autism 
spectrum 
disorder. Individuals with social 
anxiety disorder typically have adequate age-
appropriate social 
relationships and social 
communication capacity, although they may appear to 
have impairment in these areas when first interacting with unfamiliar peers or adults. 


Personality 
disorders. 
Given its frequent 
onset 
in childhood and its persistence into and through 
adulthood, social 
anxiety disorder may resemble a personality disorder. The most 
apparent 
overlap is with avoidant 
personality disorder. Individuals with avoidant 
personality disorder have 
a broader avoidance pattern and higher rates of impairment 
than those individuals with social 
anxiety disorder. Moreover, individuals with avoidant 
personality disorder have a strong and 
pervasively negative self-concept, a view of rejection as equating to a global 
evaluation of the 
self as being of little worth, and a sense of not fitting in 



235 


socially that 
dates from 
early childhood. Nonetheless, social 
anxiety disorder is typically more 
comorbid with avoidant 
personality disorder than with any other personality disorder, and 
avoidant 
personality disorder is more comorbid with social 
anxiety disorder than with any other 
anxiety disorder. 


Other mental 
disorders. 
Social 
fears and discomfort 
can occur as part 
of schizophrenia, but 
other 
evidence for psychotic symptoms is usually present. In individuals with an eating disorder, it 
is 
important 
to determine that 
fear of negative evaluation about 
eating disorder symptoms or 
behaviors (e.g., purging and vomiting) is not 
the sole source of social 
anxiety before applying a 
diagnosis of social 
anxiety disorder. Similarly, obsessive-compulsive disorder may be associated 
with social 
anxiety, but 
the additional 
diagnosis of social 
anxiety disorder is used only when 
social fears and avoidance are independent of the foci of the obsessions and compulsions. 


Other medical 
conditions. 
Medical 
conditions may produce symptoms that 
may be embarrassing 
(e.g., trembling in Parkinson s disease). When the fear of negative evaluation due to other 
medical 
conditions is judged to be excessive, a diagnosis of social 
anxiety disorder should be 
considered. 


Oppositional 
defiant 
disorder. 
Refusal to speak because of opposition to authority figures should be 
differentiated from failure to speak because of fear of negative evaluation. 


Comorbidity 


Social 
anxiety disorder is often comorbid with other anxiety disorders, major depressive 
disorder, and substance use disorders, and the onset 
of social 
anxiety disorder generally precedes 
that 
of the other disorders, except 
for specific phobia and separation anxiety disorder. Chronic 
social 
isolation in the course of social 
anxiety disorder may result 
in major depressive disorder. 
Comorbidity with depression is high also in older adults. Substances may be used as self-
medication for social 
fears, but 
the symptoms of substance intoxication or withdrawal, such as 
trembling, may also be a source of (further) social 
fear. Social 
anxiety disorder is frequently 
comorbid with body dysmorphic disorder, and generalized social 
anxiety disorder is often 
comorbid with avoidant 
personality disorder. In children, comorbidities with high-functioning 
autism spectrum disorder and selective mutism are common. 


Panic Disorder 


Diagnostic Criteria 
F41.0 


A. 
Recurrent 
unexpected 
panic attacks. 
A 
panic attack is an 
abrupt 
surge 
of 
intense 
fear or intense 
discomfort 
that 
reaches a 
peak within 
minutes, 
and 
during 
which 
time 
four (or more) of 
the 
following 
symptoms occur: 
Note: 
The 
abrupt 
surge 
can 
occur from a 
calm state 
or an 
anxious state. 


1. 
Palpitations, 
pounding 
heart, 
or accelerated 
heart 
rate. 

2. 
Sweating. 
3. 
Trembling 
or shaking. 
4. 
Sensations of 
shortness of 
breath 
or smothering. 
5. 
Feelings of 
choking. 
6. 
Chest 
pain 
or discomfort. 
7. 
Nausea 
or abdominal distress. 
8. 
Feeling 
dizzy, 
unsteady, 
light-headed, 
or faint. 
9. 
Chills or heat 
sensations. 
236 


10. 
Paresthesias (numbness or tingling 
sensations). 
11. 
Derealization 
(feelings of 
unreality) or depersonalization 
(being 
detached 
from 
oneself). 
12. 
Fear of 
losing 
control or  going 
crazy.  
13. 
Fear of 
dying. 
Note: 
Culture-specific symptoms (e.g., 
tinnitus, 
neck soreness, 
headache, 
uncontrollable 
screaming 
or crying) may be 
seen. 
Such 
symptoms should 
not 
count 
as one 
of 
the 
four required 
symptoms. 


B. 
At 
least 
one 
of 
the 
attacks has been 
followed 
by 1 
month 
(or more) of 
one 
or 
both 
of 
the 
following: 
1. 
Persistent 
concern 
or worry about 
additional panic attacks or their 
consequences (e.g., 
losing 
control, 
having 
a 
heart 
attack, 
 going 
crazy ). 
2. 
A 
significant 
maladaptive 
change 
in 
behavior related 
to 
the 
attacks (e.g., 
behaviors designed 
to 
avoid 
having 
panic attacks, 
such 
as avoidance 
of 
exercise 
or unfamiliar situations). 
C. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition 
(e.g., 
hyperthyroidism, 
cardiopulmonary disorders). 
D. 
The 
disturbance 
is not 
better explained 
by another mental disorder (e.g., 
the 
panic attacks do 
not 
occur only in 
response 
to 
feared 
social situations, 
as in 
social anxiety disorder; 
in 
response 
to 
circumscribed 
phobic objects or situations, 
as in 
specific phobia; 
in 
response 
to 
obsessions, 
as in 
obsessive-compulsive 
disorder; 
in 
response 
to 
reminders of 
traumatic events, 
as in 
posttraumatic stress 
disorder; 
or in 
response 
to 
separation 
from attachment 
figures, 
as in 
separation 
anxiety disorder). 
Diagnostic Features 


Panic disorder is characterized by recurrent 
unexpected panic attacks (Criterion A). (For a 
detailed description of symptoms and course characterizing a panic attack, see Panic Attack 



Specifier,  Features  section, following this text 
on panic disorder.) A panic attack 
is an abrupt 
surge of intense fear or intense discomfort 
that 
reaches a peak within minutes, and during which 
time 4 or more of a list 
of 13 physical 
and cognitive symptoms occur. The term 
recurrent 
means 
more than one unexpected panic attack. The term 
unexpected 
refers to a panic attack for which 
there is no obvious cue or trigger at 
the time of occurrence that 
is, the attack appears to occur 
from 
out 
of the blue, such as when the individual 
is relaxing or emerging from 
sleep (nocturnal 
panic attack). In contrast, expected 
panic attacks are those for which there is an obvious cue or 
trigger, such as a situation in which panic attacks have typically occurred. The determination of 
whether panic attacks are expected or unexpected is made by the clinician, who makes this 
judgment 
based on a combination of careful 
questioning as to the sequence of events preceding 
or leading up to the attack and the individual s own judgment 
of whether the attack seemed to 
occur for no apparent 
reason. Cultural 
interpretations may influence the assignment 
of panic 
attacks as expected or unexpected (see section  Culture-Related Diagnostic Issues  for this 
disorder). In the United States and Europe, approximately one-half of individuals with panic 
disorder have expected panic attacks as well 
as unexpected panic attacks. Thus, the presence of 
expected panic attacks does not rule out the diagnosis of panic disorder. 


The frequency and severity of panic attacks vary widely. In terms of frequency, there may be 
moderately frequent 
attacks (e.g., one per week) for months at 
a time, or short 
bursts of more 
frequent 
attacks (e.g., daily) separated by weeks or months without 
any attacks or with less 
frequent 
attacks (e.g., two per month) over many years. Individuals who have infrequent 
panic 
attacks resemble those with more frequent 
panic attacks in terms of panic attack symptoms, 
demographic characteristics, comorbidity with other disorders, family 


237 


history, and biological 
data. In terms of severity, individuals with panic disorder may have 
both full-symptom 
(four or more symptoms) and limited-symptom 
(fewer than four symptoms) 
attacks, and the number and type of panic attack symptoms frequently differ from 
one panic 
attack to the next. However, more than one unexpected full-symptom 
panic attack is required for 
the diagnosis of panic disorder. 


A nocturnal 
panic attack (i.e., waking from 
sleep in a state of panic) differs from 
panicking 
after fully waking from 
sleep. In the United States, nocturnal 
panic attack has been estimated to 
occur at 
least 
one time in roughly one-quarter to one-third of individuals with panic disorder, of 
whom 
the majority also have daytime panic attacks. Individuals with both daytime and nocturnal 
panic attacks tend to have more severe panic disorder overall. 


The worries about 
panic attacks or their consequences usually pertain to physical 
concerns, 
such as worry that 
panic attacks reflect 
the presence of life-threatening illnesses (e.g., cardiac 
disease, seizure disorder); 
social 
concerns, such as embarrassment 
or fear of being judged 
negatively by others because of visible panic symptoms; 
and concerns about 
mental 
functioning, 
such as  going crazy  or losing control 
(Criterion B). Individuals who report 
fears of dying in 
their panic attacks tend to have more severe presentations of panic disorder (e.g., panic attacks 
involving more symptoms). The maladaptive changes in behavior represent 
attempts to minimize 
or avoid panic attacks or their consequences. Examples include avoiding physical 
exertion, 
reorganizing daily life to ensure that 
help is available in the event 
of a panic attack, restricting 
usual 
daily activities, and avoiding agoraphobia-type situations, such as leaving home, using 



public transportation, or shopping. If agoraphobia is present, a separate diagnosis of agoraphobia 
is given. 


Associated Features 


In addition to worry about 
panic attacks and their consequences, many individuals with panic 
disorder report 
constant 
or intermittent 
feelings of anxiety that 
are more broadly related to health 
and mental 
health concerns. For example, individuals with panic disorder often anticipate a 
catastrophic outcome from 
a mild physical 
symptom 
or medication side effect 
(e.g., thinking that 
they may have heart 
disease or that 
a headache means presence of a brain tumor). Such 
individuals often are relatively intolerant 
of medication side effects. In addition, there may be 
pervasive concerns about 
abilities to complete daily tasks or withstand daily stressors, excessive 
use of drugs (e.g., alcohol, prescribed medications or illicit 
drugs) to control 
panic attacks, or 
extreme behaviors aimed at 
controlling panic attacks (e.g., severe restrictions on food intake or 
avoidance of specific foods or medications because of concerns about 
physical 
symptoms that 
provoke panic attacks). 


Prevalence 


In the general 
population, the 12-month prevalence estimate for panic disorder across the United 
States and several 
European countries is about 
2% 3% in adults and adolescents. The global 
lifetime prevalence is estimated at 
1.7%, with a 2.7% projected lifetime risk in the World Mental 
Health Surveys. In the United States, significantly lower prevalence estimates of panic disorder 
are reported among Latinx, African Americans, Caribbean Blacks, and Asian Americans, 
compared with non-Latinx Whites. Prevalence estimates of panic disorder in American Indians 
range from 
2.6% to 4.1%. Lower estimates have been reported for Asian, African, and Latin 
American countries, ranging from 
0.1% to 0.8%. Women are more frequently affected than men, 
at 
a rate of approximately 2:1. The gender differentiation occurs in adolescence and is already 
observable before age 14 years. Although panic attacks occur in children, the overall 
prevalence 
of panic disorder is low before age 14 years (<0.4%). The rates of panic disorder show a gradual 
increase during adolescence and possibly following the onset 
of puberty, and peak during 
adulthood. The prevalence declines in older individuals (i.e., 1.2% in adults older than age 55, 
0.7% in adults older than age 64), possibly reflecting diminishing severity to subclinical levels. 


238 


Development and Course 


The median age at 
onset 
for panic disorder in the United States is 20 24 years, and cross-
nationally is 32 years. The mean age at 
onset 
is 34.7 years. A small 
number of cases begin in 
childhood, and onset 
after age 55 years is unusual 
but 
can occur. The usual 
course, if the disorder 
is untreated, is chronic but 
waxing and waning. Some individuals may have episodic outbreaks 
with years of remission in between, and others may have continuous severe symptomatology. 
According to a longitudinal 
study in the Netherlands, about 
one-quarter of the individuals with 
panic disorder experienced recurrence of symptoms within the initial 
2-year follow-up period. 
Only a minority of individuals have full 
remission without 
subsequent 
relapse within a few 
years. The course of panic disorder typically is complicated by a range of other disorders, in 



particular other anxiety disorders, depressive disorders, and substance use disorders (see section 
 Comorbidity  for this disorder). African American adults have been reported to have a more 
chronic course of panic disorder compared with non-Latinx White adults, possibly because of the 
enduring impact 
of racism 
and discrimination, stigma due to mental 
illness, and limited access to 
adequate care. 


Although panic disorder is very rare in childhood, first 
occurrence of  fearful 
spells  is often 
dated retrospectively back to childhood. As in adults, panic disorder in adolescents tends to have 
a chronic course and is frequently comorbid with other anxiety, depressive, and bipolar 
disorders. To date, no differences in the clinical 
presentation between adolescents and adults 
have been found. However, adolescents may be less worried about 
additional 
panic attacks than 
are young adults. Lower prevalence of panic disorder in older adults appears to be attributable to 
age-related  dampening  of the autonomic nervous system 
response. Many older individuals 
with  panicky feelings  are observed to have a  hybrid  of limited-symptom 
panic attacks and 
generalized anxiety. Also, older adults tend to attribute their panic attacks to certain stressful 
situations, such as a medical 
procedure or social 
setting. Older 
individuals may retrospectively 
endorse explanations for the panic attack (which would preclude the diagnosis of panic disorder), 
even if an attack might 
actually have been unexpected in the moment 
(and thus qualify as the 
basis for a panic disorder diagnosis). This may result 
in under-endorsement 
of unexpected panic 
attacks in older individuals. Thus, careful 
questioning of older adults is required to assess 
whether panic attacks were expected before entering the situation, so that 
unexpected panic 
attacks and the diagnosis of panic disorder are not overlooked. 


While the low rate of panic disorder in children could relate to difficulties in symptom 
reporting, this seems unlikely given that 
children are capable of reporting intense fear or panic in 
relation to separation and to phobic objects or phobic situations. Adolescents might 
be less 
willing than adults to openly discuss panic attacks. Therefore, clinicians should be aware that 
unexpected panic attacks do occur in adolescents, much as they do in adults, and be attuned to 
this possibility when encountering adolescents presenting with episodes of intense fear or 
distress. 


Risk and Prognostic Factors 


Temperamental. 
Negative affectivity (neuroticism) (i.e., proneness to experiencing negative 
emotions), anxiety sensitivity (i.e., the disposition to believe that 
symptoms of anxiety are 
harmful), behavioral 
inhibition, and harm 
avoidance are risk factors for the onset 
of panic attacks 
and panic disorder. History of  fearful 
spells  (i.e., limited-symptom 
attacks that 
do not 
meet 
full 
criteria for a panic attack) may be a risk factor for later panic attacks and panic disorder, 
particularly when the first 
panic experience is appraised as negative. Although separation anxiety 
in childhood, especially when severe, may precede the later development 
of panic disorder, it 
is 
not a consistent risk factor. 


Environmental. 
Most 
individuals report 
identifiable stressors in the months before their first 
panic 
attack (e.g., interpersonal stressors and stressors related to physical well-being, 


239 


such as negative experiences with illicit 
or prescription drugs, disease, or death in the family). 



Furthermore, more chronic life stress is associated with greater panic disorder severity. Between 
10% and 60% of individuals with panic disorder endorse a history of trauma, and stressful 
life 
experiences and childhood adversities are associated with more severe panic pathology. Parental 
overprotection and low emotional 
warmth are also risk factors for panic disorder. Individuals 
with few economic resources are more likely to have symptoms that 
meet 
criteria for panic 
disorder. Smoking is a risk factor for panic attacks and panic disorder. 


Genetic 
and 
physiological. 
Multiple genes likely confer vulnerability to panic disorder; 
however, 
the exact 
genes, gene products, or functions related to the genetic regions implicated remain 
unknown. There is an increased risk for panic disorder among offspring of parents with anxiety, 
depressive, and bipolar disorders. 


Individuals with panic disorder display particularly enhanced sensitivity to respiratory 
stimulation using CO2-enriched air. Respiratory disturbance, such as asthma, may be associated 
with panic disorder, in terms of past history, comorbidity, and family history. 


Culture-Related Diagnostic Issues 


The rate of fears about 
mental 
and somatic symptoms of anxiety appears to vary across cultural 
contexts and may influence the rate of panic attacks and panic disorder. Also, cultural 
expectations may influence the classification of panic attacks as expected or unexpected. For 
example, a Vietnamese individual 
who has a panic attack after walking out 
into a windy 
environment (tr ng gi ; 
 hit 
by the wind ) may attribute the panic attack to exposure to wind as 
a result 
of the cultural 
syndrome that 
links these two experiences, resulting in classification of 
the panic attack as expected. Various other cultural 
concepts of distress are associated with panic 
disorder, including ataque de nervios 
( attack of nerves ) among Latin Americans and khy l 
attacks and  soul 
loss  among Cambodians. Ataque de nervios 
may involve trembling, 
uncontrollable screaming or crying, aggressive or suicidal 
behavior, and depersonalization or 
derealization, which may be experienced longer than the few minutes typical 
of panic attacks. 
Some clinical 
presentations of ataque de nervios 
fulfill 
criteria for conditions other than panic 
attack (e.g., functional 
neurological 
symptom 
disorder). These concepts of distress have an 
impact 
on the symptoms and frequency of panic disorder, including the individual s attribution 
of unexpectedness, as cultural 
concepts of distress may create fear of certain situations, ranging 
from 
interpersonal 
arguments (associated with ataque de nervios), to types of exertion 
(associated with khy l 
attacks), to atmospheric wind (associated with tr ng gi  
attacks). 
Clarification of the details of cultural 
attributions may aid in distinguishing expected and 
unexpected panic attacks. For more information regarding cultural 
concepts of distress, refer to 
the  Culture and Psychiatric Diagnosis  chapter in Section III. 


The specific worries about 
panic attacks or their consequences are likely to vary across 
ethnoracial 
groups and cultural 
contexts (and across different 
age groups and gender). Among 
Asian Americans, Hispanic Americans, and African Americans in the United States, panic 
disorder is associated with reports of ethnic discrimination and racism, after the effect 
of 
demographic factors is taken into account. For panic disorder, U.S. community samples of non-
Latinx Whites have significantly less functional 
impairment 
than African Americans. There are 
also higher rates of objectively defined severity in non-Latinx Caribbean Blacks with panic 
disorder, and lower reported rates of panic disorder overall 
in both African Americans and 
Caribbean Blacks, suggesting that 
among U.S. community samples of African descent, panic 



disorder criteria may be endorsed only when there is substantial 
severity and impairment. The 
rate of mental health service use for panic disorder varies across ethnoracial groups. 


Sex- and Gender-Related Diagnostic Issues 


The rate of panic disorder is nearly twofold higher in women compared with men. Relapse from 
panic disorder also occurs more frequently in adult women compared with men, 


240 


suggesting that 
women have a more unstable illness course. Gender differences in clinical 
course 
are also found among adolescents. Panic disorder has a larger impact 
on health-related quality of 
life in women than in men, which may be attributable to greater anxiety sensitivity among some 
women or greater comorbidity with agoraphobia and depression. There is some evidence for 
sexual 
dimorphism, with high expression of MAOA-uVNTR 
alleles potentially acting as a 
female-specific risk factor for panic disorder. 


Diagnostic Markers 


Individuals with panic disorder exhibit 
an attentional 
bias to threatening stimuli. Panic attacks 
may be provoked by agents with disparate mechanisms of action, such as sodium 
lactate, 
caffeine, isoproterenol, yohimbine, CO2, and cholecystokinin, to a much greater extent 
in 


individuals with panic disorder than in those without 
it. There is considerable interest 
in the 
relationship between panic disorder and sensitivity to these panic-provoking agents. While none 
of the data suggest 
diagnostic utility, data for sensitivity to respiratory stimulation reflect 
some 
level 
of specificity for panic disorder and related conditions, such as separation anxiety disorder. 
Chronically higher baseline hyperventilation and rate of sighing may occur among individuals 
with panic disorder. However, none of these laboratory findings are considered diagnostic of 
panic disorder. 


Association With Suicidal 
Thoughts or Behavior 


Panic attacks and a diagnosis of panic disorder in the past 
12 months are related to a higher rate 
of suicidal 
behavior and suicidal 
thoughts in the past 
12 months even when comorbidity and a 
history of childhood abuse and other suicide risk factors are taken into account. Approximately 
25% of primary care patients with panic disorder report 
suicidal 
thoughts. Panic disorder may 
increase risk for future suicidal behaviors but not deaths. 


Epidemiological 
survey data of panic attack symptoms show that 
the cognitive symptoms of 
panic (e.g., derealization) may be associated with suicidal 
thoughts, whereas physical 
symptoms 
(e.g., dizziness, nausea) may be associated with suicidal behaviors. 


Functional 
Consequences of Panic Disorder 


Panic disorder is associated with high levels of social, occupational, and physical 
disability; 
considerable economic costs; 
and the highest 
number of medical 
visits among the anxiety 
disorders, although the effects are strongest 
with the presence of agoraphobia. Individuals with 
panic disorder may be frequently absent 
from 
work or school 
for doctor and emergency room 



visits, which can lead to unemployment 
or dropping out 
of school. In older adults, impairment 
may be seen in caregiving duties or volunteer activities, and panic disorder is related to lower 
health-related quality of life and greater receipt of emergency department services. Full-symptom 
panic attacks typically are associated with greater morbidity (e.g., greater health care utilization, 
more disability, poorer quality of life) than limited-symptom attacks. 


Differential 
Diagnosis 


Only 
limited-symptom panic 
attacks. 
Panic disorder should not 
be diagnosed if full-symptom 
(unexpected) panic attacks have never been experienced. In the case of only limited-symptom 
unexpected panic attacks, an other specified anxiety disorder or unspecified anxiety disorder 
diagnosis should be considered. 
Anxiety 
disorder due 
to 
another medical 
condition. 
Panic disorder is not 
diagnosed if the panic 


attacks are judged to be a direct 
physiological 
consequence of another medical 
condition. 
Examples of medical 
conditions that 
can cause panic attacks include hyperthyroidism, 
hyperparathyroidism, pheochromocytoma, vestibular dysfunctions, seizure 


241 


disorders, and cardiopulmonary conditions (e.g., arrhythmias, supraventricular tachycardia, 
asthma, chronic obstructive pulmonary disease [COPD]). Appropriate laboratory tests (e.g., 
serum 
calcium 
levels for hyperparathyroidism; 
Holter monitor for arrhythmias) or physical 
examinations (e.g., for cardiac conditions) may be helpful 
in determining the etiological 
role of 
another medical 
condition. Features such as onset 
after age 45 years or the presence of atypical 
symptoms during a panic attack (e.g., vertigo, loss of consciousness, loss of bladder or bowel 
control, slurred speech, amnesia) suggest 
the possibility that 
another medical 
condition or a 
substance may be causing the panic attack symptoms. 


Substance/medication-induced 
anxiety 
disorder. 
Panic disorder is not 
diagnosed if the panic attacks 
are judged to be a direct 
physiological 
consequence of a substance. Intoxication with central 
nervous system 
stimulants (e.g., cocaine, amphetamine-type substances, caffeine) or cannabis 
and withdrawal 
from 
central 
nervous system 
depressants (e.g., alcohol, barbiturates) can 
precipitate a panic attack. 


However, if panic attacks continue to occur outside of the context 
of substance use (e.g., long 
after the effects of intoxication or withdrawal 
have ended), a diagnosis of panic disorder should 
be considered. In addition, because panic disorder may precede substance use in some 
individuals and may be associated with increased substance use, especially for purposes of self-
medication, a detailed history should be taken to determine if the individual 
had panic attacks 
prior to excessive substance use. If this is the case, a diagnosis of panic disorder should be 
considered in addition to a diagnosis of substance use disorder. Features such as onset 
after age 
45 years or the presence of atypical 
symptoms during a panic attack (e.g., vertigo, loss of 
consciousness, loss of bladder or bowel 
control, slurred speech, amnesia) suggest 
the possibility 
that another medical condition or a substance may be causing the panic attack symptoms. 
Other mental 
disorders 
with 
panic 
attacks 
as 
an 
associated 
feature 
(e.g., 
other anxiety 
disorders 
and 
psychotic 
disorders).

Panic attacks that 
occur as a symptom 
of other anxiety disorders are expected (e.g., triggered by 



social 
situations in social 
anxiety disorder, by phobic objects or situations in specific phobia or 
agoraphobia, by worry in generalized anxiety disorder, by separation from 
home or attachment 
figures in separation anxiety disorder) and thus would not 
meet 
criteria for panic disorder. (Note: 
Sometimes an unexpected panic attack is associated with the onset 
of another anxiety disorder, 
but 
then the attacks become expected, whereas panic disorder is characterized by recurrent 
unexpected panic attacks.) If the panic attacks occur only in response to specific triggers, then 
only the relevant 
anxiety disorder is assigned. However, if the individual 
experiences unexpected 
panic attacks as well 
and shows persistent 
concern and worry or behavioral 
change because of 
the attacks, then an additional diagnosis of panic disorder should be considered. 


Comorbidity 


Panic disorder infrequently occurs in clinical settings in the absence of other psychopathology. In 
the general 
population, 80% of individuals with panic disorder had a lifetime comorbid mental 
diagnosis. The prevalence of panic disorder is elevated in individuals with other disorders, 
particularly other anxiety disorders (and especially agoraphobia), major depressive disorder, 
bipolar I and bipolar II disorder, and possibly mild alcohol 
use disorder. While panic disorder 
occasionally has an earlier age at onset than the comorbid disorder(s), onset often occurs after the 
comorbid disorder and may be seen as a severity marker of the comorbid illness. 


Reported lifetime rates of comorbidity between major depressive disorder and panic disorder 
vary widely, ranging from 
10% to 65% in individuals with panic disorder. In approximately one-
third of individuals with both disorders, the depression precedes the onset 
of panic disorder. In 
the remaining two-thirds, depression occurs coincident 
with or following the onset 
of panic 
disorder. A subset of individuals with panic disorder develop a 


242 


substance-related disorder, which for some represents an attempt 
to treat 
their anxiety with 
alcohol 
or medications. Comorbidity with other anxiety disorders and illness anxiety disorder is 
also common. 


Panic disorder is significantly comorbid with numerous general 
medical 
symptoms and 
conditions, including, but 
not 
limited to, dizziness, cardiac arrhythmias, hyperthyroidism, 
asthma, COPD, and irritable bowel 
syndrome. However, the nature of the association (e.g., cause 
and effect) between panic disorder and these conditions remains unclear. Although mitral 
valve 
prolapse and thyroid disease are more common among individuals with panic disorder than in the 
general population, the increases in prevalence are not consistent. 


Panic Attack Specifier 


Note: 
Symptoms are 
presented 
for the 
purpose 
of 
identifying 
a 
panic attack; 
however, 
panic attack is not 
a 
mental disorder and 
cannot 
be 
coded. 
Panic attacks 
can 
occur in 
the 
context 
of 
any anxiety disorder as well as other mental disorders 
(e.g., 
depressive 
disorders, 
posttraumatic stress disorder, 
substance 
use 
disorders) 
and 
some 
medical conditions (e.g., 
cardiac, 
respiratory, 
vestibular, 
gastrointestinal). 
When 
the 
presence 
of 
a 
panic attack is identified, 
it 
should 
be 
noted 
as a 
specifier 



(e.g., 
 posttraumatic stress disorder with 
panic attacks ). 
For panic disorder, 
the 
presence 
of 
panic attack is contained 
within 
the 
criteria 
for the 
disorder and 
panic 
attack is not 
used 
as a 
specifier. 


An 
abrupt 
surge 
of 
intense 
fear or intense 
discomfort 
that 
reaches a 
peak within 
minutes, 
and 
during 
which 
time 
four (or more) of 
the 
following 
symptoms occur: 
Note: 
The 
abrupt 
surge 
can 
occur from a 
calm state 
or an 
anxious state. 
1. 


1. 
Palpitations, 
pounding 
heart, 
or accelerated 
heart 
rate. 
2. 
Sweating. 
3. 
Trembling 
or shaking. 
4. 
Sensations of 
shortness of 
breath 
or smothering. 
5. 
Feelings of 
choking. 
6. 
Chest 
pain 
or discomfort. 
7. 
Nausea 
or abdominal distress. 
8. 
Feeling 
dizzy, 
unsteady, 
light-headed, 
or faint. 
9. 
Chills or heat 
sensations. 
10. 
Paresthesias (numbness or tingling 
sensations). 
11. 
Derealization 
(feelings of 
unreality) or depersonalization 
(being 
detached 
from 
oneself). 
12. 
Fear of 
losing 
control or  going 
crazy.  
13. 
Fear of 
dying. 
Note: 
Culture-specific symptoms (e.g., 
tinnitus, 
neck soreness, 
headache, 
uncontrollable 
screaming 
or crying) may be 
seen. 
Such 
symptoms should 
not 
count 
as one 
of 
the 
four required 
symptoms. 


Features 


The essential 
feature of a panic attack is an abrupt 
surge of intense fear or intense discomfort 
that 
reaches a peak within minutes and during which time 4 or more of 13 physical 
and cognitive 
symptoms occur. Eleven of these 13 symptoms are physical 
(e.g., palpitations, sweating), while 2 
are cognitive (i.e., fear of losing control 
or going crazy, fear of dying).  Fear of going crazy  is a 
colloquialism 
often used by individuals with panic attacks and is not 
intended as a pejorative or 
diagnostic term. The term 
within minutes 
means that 
the time to peak intensity is literally only a 
few minutes. A panic attack can arise from either a calm state or an 


243 


anxious state, and time to peak intensity should be assessed independently of any preceding 
anxiety. That 
is, the start 
of the panic attack is the point 
at 
which there is an abrupt 
increase in 
discomfort 
rather than the point 
at 
which anxiety first 
developed. Likewise, a panic attack can 
return to either an anxious state or a calm 
state and possibly peak again. A panic attack is 
distinguished from 
ongoing anxiety by its time to peak intensity, which occurs within minutes; 
its discrete nature; 
and its typically greater severity. Attacks that 
meet 
all 
other criteria but 
have 
fewer than four physical and/or cognitive symptoms are referred to as limited-symptom attacks. 



There are two characteristic types of panic attacks: 
expected and unexpected. Expected panic 
attacks 
are attacks for which there is an obvious cue or trigger, such as situations in which panic 
attacks have typically occurred. Unexpected panic attacks 
are those for which there is no obvious 
cue or trigger at 
the time of occurrence (e.g., when relaxing or out 
of sleep [nocturnal 
panic 
attack]). The determination of whether panic attacks are expected or unexpected is made by the 
clinician, who makes this judgment 
based on a combination of careful 
questioning as to the 
sequence of events preceding or leading up to the attack and the individual s own judgment 
of 
whether the attack seemed to occur for no apparent 
reason. Panic attacks can occur in the context 
of any mental 
disorder (e.g., anxiety disorders, depressive disorders, bipolar disorders, eating 
disorders, obsessive-compulsive and related disorders, personality disorders, psychotic disorders, 
substance use disorders) and some medical 
conditions (e.g., cardiac, respiratory, vestibular, 
gastrointestinal), with the majority of presentations never meeting criteria for panic disorder. 
Recurrent unexpected panic attacks are required for a diagnosis of panic disorder. 


Associated Features 


One type of unexpected panic attack is a nocturnal 
panic attack 
(i.e., waking from 
sleep in a 
state of panic), which differs from panicking after fully waking from sleep. 


Prevalence 


In the general 
population, 12-month prevalence estimates for panic attacks in Spain and in the 
United States range from 
9.5% to 11.2% in adults. Twelve-month prevalence estimates do not 
appear to differ significantly among African Americans, Asian Americans, and Latinx. 
Approximately 8.5% of American Indians report 
a lifetime history of panic attacks. Lifetime 
prevalence rates of panic attacks cross-nationally are 13.2%. Women are more frequently 
affected than men, although this gender difference is more pronounced for panic disorder. Panic 
attacks can occur in children but 
are relatively rare until 
the age of puberty, when the prevalence 
rates increase. The prevalence declines in older individuals, possibly reflecting diminishing 
severity to subclinical levels. 


Development and Course 


The mean age at 
onset 
for panic attacks in the United States is approximately 22 23 years among 
adults. However, the course of panic attacks is likely influenced by the course of any co-
occurring mental 
disorder(s) and stressful 
life events. Panic attacks are uncommon, and 
unexpected panic attacks are rare, in preadolescent 
children. Adolescents might 
be less willing 
than adults to openly discuss panic attacks, even though they present 
with episodes of intense 
fear or discomfort. Lower prevalence of panic attacks in older individuals may be related to a 
weaker autonomic response to emotional 
states relative to younger individuals. Older individuals 
may be less inclined to use the word  fear  and more inclined to use the word  discomfort  to 
describe panic attacks. Older individuals with  panicky feelings  may have a hybrid of limited-
symptom 
attacks and generalized anxiety. In addition, older individuals tend to attribute panic 
attacks to certain situations that 
are stressful 
(e.g., medical 
procedures, social 
settings) and may 
retrospectively endorse explanations for the panic attack even if it 
was unexpected in the 
moment. This may result in under-endorsement of unexpected panic attacks in older individuals. 



244 


Risk and Prognostic Factors 


Temperamental. 
Negative affectivity (neuroticism) (i.e., proneness to experiencing negative 
emotions), anxiety sensitivity (i.e., the disposition to believe that 
symptoms of anxiety are 
harmful), behavioral 
inhibition, and harm 
avoidance are risk factors for the onset 
of panic 
attacks. History of  fearful 
spells  (i.e., limited-symptom 
attacks that 
do not 
meet 
full 
criteria for 
a panic attack) may be a risk factor for later panic attacks. 


Environmental. 
Smoking is a risk factor for panic attacks. Most 
individuals report 
identifiable 
stressors in the months before their first 
panic attack (e.g., interpersonal 
stressors and stressors 
related to physical 
well-being, such as negative experiences with illicit 
or prescription drugs, 
disease, or death in the family). Separation from 
parents, overprotective parenting, and parental 
rejection are risk factors for panic attacks. 


Genetic 
and 
physiological. 
Individuals with chronic obstructive pulmonary disease who report 
low 
perceptions of control 
over the disease and negative beliefs about 
the consequences of 
unpredictable breathless attacks are more likely to have panic symptoms. 


Culture-Related Diagnostic Issues 


Cultural 
interpretations may influence the determination of panic attacks as expected or 
unexpected. Culture-specific symptoms (e.g., tinnitus, neck soreness, headache, and 
uncontrollable screaming or crying) may be seen; 
however, such symptoms should not 
count 
as 
one of the four required symptoms. Frequency of each of the 13 symptoms varies cross-
culturally (e.g., higher rates of paresthesias in African Americans, of dizziness in several 
Asian 
groups, and of trembling in non-Latinx Whites). Cultural 
concepts of distress also influence the 
cross-cultural 
presentation of panic attacks, resulting in different 
symptom 
profiles across 
different 
cultural 
groups. Examples include khy l 
(wind) attacks, a Cambodian cultural 
syndrome involving dizziness, tinnitus, and neck soreness; 
and tr ng gi  
(wind-related) attacks, 
a Vietnamese cultural 
syndrome associated with headaches. Cultural 
explanatory models can 
heighten the salience of specific panic symptoms. For example, traditional 
Cambodian views 
about 
the abnormal 
circulation of khy l 
in the body are associated with the perceived 
dangerousness of some symptoms (e.g., neck soreness), which can trigger catastrophic 
cognitions and panic attacks. Ataque de nervios 
(attack of nerves) is a cultural 
syndrome among 
Latin Americans that 
may involve trembling, uncontrollable screaming or crying, aggressive or 
suicidal 
behavior, and depersonalization or derealization, and which may be experienced for 
longer than only a few minutes. Some clinical 
presentations of ataque de nervios 
fulfill 
criteria 
for conditions other than panic attack (e.g., other specified dissociative disorder). Also, cultural 
expectations may influence the classification of panic attacks as expected or unexpected, as 
cultural 
syndromes may create fear of certain situations, ranging from 
interpersonal 
arguments 
(associated with ataque de nervios), to types of exertion (associated with khy l 
attacks), to 
atmospheric wind (associated with tr ng gi  
attacks). Clarification of the details of cultural 
attributions may aid in distinguishing expected and unexpected panic attacks. For more 
information about 
cultural 
concepts of distress, see the  Culture and Psychiatric Diagnosis  
chapter in Section III. 



Sex- and Gender-Related Diagnostic Issues 


Panic attacks are more common in women than in men. Among those who report 
panic attacks, 
women are more likely to endorse symptoms of shortness of breath and nausea but 
less likely to 
endorse sweating than are men. 


Diagnostic Markers 


Physiological 
recordings of naturally occurring panic attacks in individuals with panic disorder 
indicate abrupt surges of arousal, usually of heart rate, that reach a peak within 


245 


minutes and subside within minutes, and for a proportion of these individuals the panic attack 
may be preceded by cardiorespiratory instabilities. Panic attacks are characterized by heart 
rate 
and tidal volume increases and a drop in pCO2. 


Association With Suicidal 
Thoughts or Behavior 


Panic attacks are related to a higher rate of suicide attempts and suicidal 
thoughts even when 
comorbidity and other suicide risk factors are taken into account. 


Functional 
Consequences of Panic Attacks 


In the context 
of co-occurring mental 
disorders, including anxiety disorders, depressive 
disorders, bipolar disorder, substance use disorders, psychotic disorders, and personality 
disorders, panic attacks are associated with increased symptom 
severity, higher rates of 
comorbidity, and poorer treatment 
response. Recurrent 
panic attacks in particular are associated 
with increased odds of many mental 
health diagnoses. Furthermore, more severe panic attacks 
are associated with a greater likelihood of developing panic disorder and a variety of other 
mental 
health conditions, as well 
as greater persistence of mental 
illness and impaired 
functioning. Also, full-symptom 
panic attacks typically are associated with greater morbidity 
(e.g., greater health care utilization, more disability, poorer quality of life) than limited-symptom 
attacks. 


Differential 
Diagnosis 


Other paroxysmal 
episodes 
(e.g., 
 anger attacks ). 
Panic attacks should not 
be diagnosed if the 
episodes do not 
involve the essential 
feature of an abrupt 
surge of intense fear or intense 
discomfort, but rather other emotional states (e.g., anger, grief). 


Anxiety 
disorder due 
to 
another medical 
condition. 


Medical 
conditions that 
can 
cause or be 
misdiagnosed as panic attacks include hyperthyroidism, hyperparathyroidism, 
pheochromocytoma, vestibular dysfunctions, seizure disorders, and cardiopulmonary conditions 
(e.g., arrhythmias, supraventricular tachycardia, asthma, chronic obstructive pulmonary disease). 
Appropriate laboratory tests (e.g., serum 
calcium 
levels for hyperparathyroidism; 
Holter monitor 
for arrhythmias) or physical 
examinations (e.g., for cardiac conditions) may be helpful 
in 
determining the etiological role of another medical condition. 



Substance/medication-induced 
anxiety 
disorder. 
Intoxication with central 
nervous system 
stimulants 
(e.g., cocaine, amphetamine-type substances, caffeine) or cannabis and withdrawal 
from 
central 
nervous system 
depressants (e.g., alcohol, barbiturates) can precipitate a panic attack. A detailed 
history should be taken to determine if the individual 
had panic attacks prior to excessive 
substance use. Features such as onset 
after age 45 years or the presence of atypical 
symptoms 
during a panic attack (e.g., vertigo, loss of consciousness, loss of bladder or bowel 
control, 
slurred speech, or amnesia) suggest 
the possibility that 
a medical 
condition or a substance may 
be causing the panic attack symptoms. 


Panic 
disorder. 
Repeated unexpected panic attacks are required but 
are not 
sufficient 
for the 
diagnosis of panic disorder (i.e., full diagnostic criteria for panic disorder must be met). 


Comorbidity 


Panic attacks are associated with increased likelihood of various comorbid mental 
disorders, 
including anxiety disorders, depressive disorders, bipolar disorders, impulse-control 
disorders, 
and substance use disorders. Panic attacks are associated with increased likelihood of later 
developing anxiety disorders, depressive disorders, bipolar disorders, alcohol 
use disorder, and 
possibly other disorders. 


246 


Agoraphobia 


Diagnostic Criteria 
F40.00 


A. 
Marked 
fear or anxiety about 
two 
(or more) of 
the 
following 
five 
situations: 
1. 
Using 
public transportation 
(e.g., 
automobiles, 
buses, 
trains, 
ships, 
planes). 
2. 
Being 
in 
open 
spaces (e.g., 
parking 
lots, 
marketplaces, 
bridges). 
3. 
Being 
in 
enclosed 
places (e.g., 
shops, 
theaters, 
cinemas). 
4. 
Standing 
in 
line 
or being 
in 
a 
crowd. 
5. 
Being 
outside 
of 
the 
home 
alone. 
B. 
The 
individual fears or avoids these 
situations because 
of 
thoughts that 
escape 
might 
be 
difficult 
or help 
might 
not 
be 
available 
in 
the 
event 
of 
developing 
panic-
like 
symptoms or other incapacitating 
or embarrassing 
symptoms (e.g., 
fear of 
falling 
in 
the 
elderly; 
fear of 
incontinence). 
C. 
The 
agoraphobic situations almost 
always provoke 
fear or anxiety. 
D. 
The 
agoraphobic situations are 
actively avoided, 
require 
the 
presence 
of 
a 
companion, 
or are 
endured 
with 
intense 
fear or anxiety. 
E. 
The 
fear or anxiety is out 
of 
proportion 
to 
the 
actual danger posed 
by the 
agoraphobic situations and 
to 
the 
sociocultural context. 
F. 
The 
fear, 
anxiety, 
or avoidance 
is persistent, 
typically lasting 
for 6 
months or 

more. 


G. 
The 
fear, 
anxiety, 
or avoidance 
causes clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
H. 
If 
another medical condition 
(e.g., 
inflammatory bowel disease, 
Parkinson s 
disease) is present, 
the 
fear, 
anxiety, 
or avoidance 
is clearly excessive. 
I. 
The 
fear, 
anxiety, 
or avoidance 
is not 
better explained 
by the 
symptoms of 
another mental disorder for example, 
the 
symptoms are 
not 
confined 
to 
specific 
phobia, 
situational type; 
do 
not 
involve 
only social situations (as in 
social anxiety 
disorder); 
and 
are 
not 
related 
exclusively to 
obsessions (as in 
obsessive-
compulsive 
disorder), 
perceived 
defects or flaws in 
physical appearance 
(as in 
body dysmorphic disorder), 
reminders of 
traumatic events (as in 
posttraumatic 
stress disorder), 
or fear of 
separation 
(as in 
separation 
anxiety disorder). 
Note: 
Agoraphobia 
is diagnosed 
irrespective 
of 
the 
presence 
of 
panic disorder. 
If 
an 
individual s presentation 
meets criteria 
for panic disorder and 
agoraphobia, 
both 
diagnoses should 
be 
assigned. 


Diagnostic Features 


The essential 
feature of agoraphobia is marked fear or anxiety triggered by the real 
or anticipated 
exposure to a wide range of situations (Criterion A). The diagnosis requires endorsement 
of 
symptoms occurring in at 
least 
two of the following five situations: 
1) using public 
transportation, such as automobiles, buses, trains, ships, or planes; 
2) being in open spaces, such 
as parking lots, marketplaces, or bridges; 
3) being in enclosed spaces, such as shops, theaters, or 
cinemas; 
4) standing in line or being in a crowd; 
or 5) being outside of the home alone. The 
examples for each situation are not 
exhaustive; 
other situations may be feared. When 
experiencing fear and anxiety cued by such situations, individuals typically experience thoughts 
that 
something terrible might 
happen (Criterion B). Individuals frequently believe that 
escape 
from 
such situations might 
be difficult 
(e.g.,  can t 
get 
out 
of here ) or that 
help might 
be 
unavailable (e.g.,  there is nobody to help me ) when panic-like symptoms or other 
incapacitating or embarrassing symptoms occur.  Panic-like symptoms  refer to any of the 13 
symptoms included in the criteria for panic attack, such as dizziness, faintness, and fear of dying. 
 Other incapacitating or embarrassing symptoms  include 


247 


symptoms such as vomiting and inflammatory bowel 
symptoms, as well 
as, in older adults, a fear 
of falling or, in children, a sense of disorientation and getting lost. 


The amount 
of fear experienced may vary with proximity to the feared situation and may 
occur in anticipation of or in the actual 
presence of the agoraphobic situation. Also, the fear or 
anxiety may take the form 
of a full- or limited-symptom 
panic attack (i.e., an expected panic 
attack). Fear or anxiety is evoked nearly every time the individual 
comes into contact 
with the 
feared situation (Criterion C). Thus, an individual 
who becomes anxious only occasionally in an 
agoraphobic situation (e.g., becomes anxious when standing in line on only one out 
of every five 
occasions) would not 
be diagnosed with agoraphobia. The individual 
actively avoids the 



situation, requires the presence of a companion, or, if he or she either is unable or decides not 
to 
avoid it, the situation evokes intense fear or anxiety (Criterion D). Active avoidance 
means the 
individual 
is currently behaving in ways that 
are intentionally designed to prevent 
or minimize 
contact 
with agoraphobic situations. Avoidance can be behavioral 
(e.g., changing daily routines, 
choosing a job nearby to avoid using public transportation, arranging for food delivery to avoid 
entering shops and supermarkets) as well 
as cognitive (e.g., using distraction to get 
through 
agoraphobic situations) in nature. The avoidance can become so severe that 
the individual 
is 
completely homebound. Often, an individual 
is better able to confront 
a feared situation when 
accompanied by a companion, such as a partner, friend, or health professional. Also, the 
individual 
may employ safety behaviors (e.g., sitting near exits when taking public transportation 
or at the movies) to better endure such situations. 


The fear, anxiety, or avoidance must 
be out 
of proportion to the actual 
danger posed by the 
agoraphobic situations and to the sociocultural 
context 
(Criterion E). Differentiating 
disproportionate, clinically significant 
agoraphobic fears from 
reasonable fears (e.g., not 
wanting 
to leave the house during a bad storm) or from 
situations that 
are deemed dangerous (e.g., 
walking in a parking lot 
or using public transportation in a high-crime area) is important 
for a 
number of reasons. First, what constitutes avoidance may be difficult to judge across cultures and 
sociocultural 
contexts (e.g., it 
is socioculturally appropriate for orthodox Muslim 
women in 
certain parts of the world to avoid leaving the house alone, and thus such avoidance would not 
be 
considered indicative of agoraphobia). Second, older adults are likely to overattribute their fears 
to age-related constraints and are less likely to judge their fears as being out 
of proportion to the 
actual 
risk. Third, individuals with agoraphobia are likely to overestimate danger in relation to 
panic-like or other bodily symptoms. Agoraphobia should be diagnosed only if the fear, anxiety, 
or avoidance is persistent 
(Criterion F) and if it 
causes clinically significant 
distress or 
impairment 
in social, occupational, or other important 
areas of functioning (Criterion G). The 
duration of  typically lasting for 6 months or more  is meant 
to exclude individuals with short-
lived, transient problems. 


Associated Features 


In its most 
severe forms, agoraphobia can cause individuals to become completely homebound, 
unable to leave their home and dependent 
on others for services or assistance to provide even for 
basic needs. Demoralization and depressive symptoms, as well 
as abuse of alcohol 
and sedative 
medication as inappropriate self-medication strategies, are common. 


Prevalence 


Every year approximately 1% 1.7% of adolescents and adults worldwide have symptoms that 
meet 
diagnostic criteria for agoraphobia. Women are twice as likely as men to experience 
agoraphobia. Agoraphobia may occur in childhood, but 
incidence peaks in late adolescence and 
early adulthood. Studies have shown the 12-month prevalence in individuals living in the United 
States who are older than 65 years is 0.4% and 0.5% among individuals in Europe and North 
America older than 55 years. Approximately 0.2% 0.8% of 


248 



the adult 
population in various countries has a past 
12-month diagnosis of agoraphobia without 
panic disorder. 


Development and Course 


The percentage of individuals with agoraphobia reporting panic attacks or panic disorder 
preceding the onset 
of agoraphobia ranges from 
30% in community samples to more than 50% in 
clinical samples. 


In two-thirds of all 
cases of agoraphobia, initial 
onset 
is before age 35 years, with 21 years 
the mean age at 
onset, although age at 
onset 
of agoraphobia without 
preceding panic attacks or 
panic disorder is 25 29 years. First 
onset 
in childhood is rare. There is a substantial 
incidence 
risk in adolescence and early adulthood, with indications for a second high incidence risk phase 
after age 40 years. Approximately 10% of older adults with agoraphobia reported their first 
episode of agoraphobia occurring after age 65. 


The course of agoraphobia is typically persistent 
and chronic. Complete remission is rare 
(10%), unless the agoraphobia is treated. Individuals with comorbid panic disorder and 
agoraphobia are more likely to experience recurrence of symptoms after a period of remission if 
they had an earlier age at 
onset 
(< 20 years old). With more severe agoraphobia, rates of full 
remission decrease, whereas rates of relapse and chronicity increase. Approximately 36% of 
individuals with agoraphobia who achieve remission eventually experience relapse. A range of 
other disorders, in particular other anxiety disorders, depressive disorders, substance use 
disorders, and personality disorders, may complicate the course of agoraphobia. The long-term 
course and outcome of agoraphobia are associated with substantially elevated risk of secondary 
major depressive disorder, persistent depressive disorder, and substance use disorders. 


The clinical 
features of agoraphobia are relatively consistent 
across the life span, although 
the type of agoraphobic situations triggering fear, anxiety, or avoidance, as well 
as the type of 
cognitions, may vary. For example, in children, being outside of the home alone is the most 
frequent 
situation feared, whereas in older adults, being in shops, standing in line, and being in 
open spaces are most 
often feared. Also, cognitions often pertain to becoming lost 
(in children), 
to experiencing panic-like symptoms (in adults), to falling (in older adults). 


The apparent 
low prevalence of agoraphobia in children could reflect 
difficulties in symptom 
reporting, and thus assessments in young children may require solicitation of information from 
multiple sources, including parents or teachers. Adolescents, particularly boys, may be less 
willing than adults to openly discuss agoraphobic fears and avoidance; 
however, agoraphobia 
can occur before adulthood and should be assessed in children and adolescents. In older adults, 
comorbid somatic symptom 
disorder, having medical 
complications, and motor disturbances 
(e.g., a sense of falling) are frequently mentioned by individuals as the reason for their fear and 
avoidance. In these instances, care is to be taken in evaluating whether the fear and avoidance are 
out of proportion to the real danger involved. 


Risk and Prognostic Factors 


Temperamental. 
Behavioral 
inhibition, negative affectivity (neuroticism), anxiety sensitivity, and 
trait 
anxiety are closely associated with agoraphobia but 
are relevant 
to most 
anxiety disorders 
(specific phobia, social 
anxiety disorder, panic disorder, generalized anxiety disorder). Anxiety 
sensitivity (the disposition to believe that 
symptoms of anxiety are harmful) is also characteristic 



of individuals with agoraphobia. 
Environmental. 
Negative events in childhood (e.g., separation, death of parent) and other stressful 
events, such as being attacked or mugged, are associated with the onset 
of agoraphobia. 
Furthermore, individuals with agoraphobia describe the family climate and child-rearing 
behavior as being characterized by reduced warmth and increased overprotection. 


249 


Genetic 
and 
physiological. 
Heritability for agoraphobia is 61%. Of the various phobias, 
agoraphobia has the strongest 
and most 
specific association with the genetic factor that 
represents proneness to phobias. Family history of anxiety disorders is associated with an earlier 
age at 
onset 
of agoraphobia (< 27 years old), and family history of panic disorder in particular is 
associated with agoraphobia. 


Sex- and Gender-Related Diagnostic Issues 


Women have different 
patterns of comorbid disorders than men. Consistent 
with gender 
differences in the prevalence of mental 
disorders, men have higher rates of comorbid substance 
use disorders. 


Association With Suicidal 
Thoughts or Behavior 


Approximately 15% of individuals with agoraphobia report 
suicidal 
thoughts or behavior. For 
individuals with panic disorder, symptoms of agoraphobia may be a risk factor for suicidal 
thoughts. 


Functional 
Consequences of Agoraphobia 


Like most 
other anxiety disorders, agoraphobia is associated with considerable impairment 
and 
disability in terms of role functioning, work productivity, and disability days. Agoraphobia 
severity is a strong determinant 
of the degree of disability, irrespective of the presence of 
comorbid panic disorder, panic attacks, and other comorbid conditions. Individuals with 
agoraphobia can be completely homebound or unable to work. Individuals with panic disorder 
with agoraphobia who have an early course of onset 
(< age 20 years) are less likely to be 
married. 


Differential 
Diagnosis 


Specific 
phobia, 
situational 
type. 
Differentiating agoraphobia from 
situational 
specific phobia can 
be challenging in some cases, because these conditions share several 
symptom 
characteristics 
and criteria. Specific phobia, situational 
type, should be diagnosed versus agoraphobia if the fear, 
anxiety, or avoidance is limited to one of the agoraphobic situations. Requiring fears from 
two or 
more of the agoraphobic situations is a robust 
means for differentiating agoraphobia from 
specific phobias, particularly the situational 
subtype. Additional 
differentiating features include 
the content 
of the individual s cognitions. Thus, if the situation is feared for reasons other than 
panic-like symptoms or other incapacitating or embarrassing symptoms (e.g., fears of being 
directly harmed by the situation itself, such as fear of the plane crashing for individuals who fear 



fl 


Se 


agoraphobi 
thought 
ot 
incapaci 


So 


pri 
cogni 


Pa 


the 
m 


Ac 


st 
anxi 
If 
does 
warrant 


M 


because 
to 
not 


Av 


avoi 
indi 
wi 
avoi 


Comorbi 


About 
addi 
anxi 
di 
pani 
di 
precedes 
tend 
agoraphobi 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
263 



Obsessive-Compulsive and Related Disorders 


Obsessive-compulsive and related disorders 
include obsessive-
compulsive disorder (OCD), body dysmorphic disorder, hoarding disorder, trichotillomania 
(hair-pulling disorder), excoriation (skin-picking) disorder, substance/medication-induced 
obsessive-compulsive and related disorder, obsessive-compulsive and related disorder due to 
another medical 
condition, other specified obsessive-compulsive and related disorder (e.g., nail 
biting, lip biting, cheek chewing, obsessional 
jealousy, olfactory reference disorder [olfactory 
reference syndrome]), and unspecified obsessive-compulsive and related disorder. 


OCD is characterized by the presence of obsessions and/or compulsions. Obsessions 
are 
recurrent 
and persistent 
thoughts, urges, or images that 
are experienced as intrusive and 
unwanted, whereas compulsions 
are repetitive behaviors or mental 
acts that 
an individual 
feels 
driven to perform 
in response to an obsession or according to rules that 
must 
be applied rigidly. 
Some other obsessive-compulsive and related disorders are also characterized by preoccupations 
and by repetitive behaviors or mental 
acts in response to the preoccupations. Other obsessive-
compulsive and related disorders are characterized primarily by recurrent 
body-focused 
repetitive behaviors (e.g., hair pulling, skin picking) and repeated attempts to decrease or stop the 
behaviors. 


The inclusion of a chapter on obsessive-compulsive and related disorders in DSM-5 reflects 
the increasing evidence of these disorders  relatedness to one another in terms of a range of 
diagnostic validators as well 
as the clinical 
utility of grouping these disorders in the same 
chapter. Clinicians are encouraged to screen for these conditions in individuals who present 
with 
one of them 
and be aware of overlaps among these conditions. At 
the same time, there are 
important 
differences in diagnostic validators and treatment 
approaches across these disorders. 
Moreover, there are close relationships between the anxiety disorders and some of the obsessive-
compulsive and related disorders (e.g., OCD), which is reflected in the sequence of DSM-5 
chapters, with obsessive-compulsive and related disorders following anxiety disorders. 


The obsessive-compulsive and related disorders differ from 
developmentally normative 
preoccupations and rituals by being excessive or persisting beyond developmentally appropriate 
periods. The distinction between the presence of subclinical 
symptoms and a clinical 
disorder 
requires assessment 
of a number of factors, including the individual s level 
of distress and 
impairment in functioning. 


The chapter begins with OCD. It 
then covers body dysmorphic disorder and hoarding 
disorder, which are characterized by cognitive symptoms such as perceived defects or flaws in 
physical 
appearance or the perceived need to save possessions, respectively. The chapter then 
covers trichotillomania and excoriation disorder, which are characterized by recurrent 
body-
focused repetitive behaviors. Finally, it 
covers substance/medication-induced obsessive-
compulsive and related disorder, obsessive-compulsive and related disorder due to another 
medical 
condition, other specified obsessive-compulsive and related disorder, and unspecified 



obsessive-compulsive and related disorder. 


264 


While the specific content 
of obsessions and compulsions varies among individuals, certain 
symptom 
dimensions are common in OCD, including those of cleaning (contamination 
obsessions and cleaning compulsions); 
symmetry (symmetry obsessions and repeating, ordering, 
and counting compulsions); 
forbidden or taboo thoughts (e.g., aggressive, sexual, and religious 
obsessions and related compulsions); 
and harm 
(e.g., fears of harm 
to self or others and related 
checking compulsions). The tic-related specifier of OCD is used when an individual 
has a 
current or past history of a tic disorder. 


Body dysmorphic disorder is characterized by preoccupation with one or more perceived 
defects or flaws in physical 
appearance that 
are not 
observable or appear only slight 
to others, 
and by repetitive behaviors (e.g., mirror checking, excessive grooming, skin picking, or 
reassurance seeking) or mental 
acts (e.g., comparing one s appearance with that 
of other people) 
in response to the appearance concerns. The appearance preoccupations are not 
better explained 
by concerns with body fat 
or weight 
in an individual 
with an eating disorder. Muscle dysmorphia 
is a form 
of body dysmorphic disorder that 
is characterized by the belief that 
one s body build is 
too small or is insufficiently muscular. 


Hoarding disorder is characterized by persistent 
difficulty discarding or parting with 
possessions, regardless of their actual 
value, as a result 
of a strong perceived need to save the 
items and distress associated with discarding them. Hoarding disorder differs from 
normal 
collecting. For example, symptoms of hoarding disorder result 
in the accumulation of a large 
number of possessions that 
congest 
and clutter active living areas to the extent 
that 
their intended 
use is substantially compromised. The excessive acquisition form 
of hoarding disorder, which 
characterizes most 
but 
not 
all 
individuals with hoarding disorder, consists of excessive 
collecting, buying, or stealing of items that 
are not 
needed or for which there is no available 
space. 


Trichotillomania is characterized by recurrent 
pulling out 
of one's hair resulting in hair loss, 
and repeated attempts to decrease or stop hair pulling. Excoriation disorder is characterized by 
recurrent 
picking of one s skin resulting in skin lesions and repeated attempts to decrease or stop 
skin picking. The body-focused repetitive behaviors that 
characterize these two disorders are not 
triggered by obsessions or preoccupations; 
however, they may be preceded or accompanied by 
various emotional 
states, such as feelings of anxiety or boredom. They may also be preceded by 
an increasing sense of tension or may lead to gratification, pleasure, or a sense of relief when the 
hair is pulled out 
or the skin is picked. Individuals with these disorders may have varying 
degrees of conscious awareness of the behavior while engaging in it, with some individuals 
displaying more focused attention on the behavior (with preceding tension and subsequent 
relief) 
and other individuals displaying more automatic behavior (with the behaviors seeming to occur 
without full awareness). 


Substance/medication-induced obsessive-compulsive and related disorder consists of 
symptoms characteristic of the obsessive-compulsive and related disorders developed in the 
context 
of substance intoxication or withdrawal 
or after exposure to or withdrawal 
from 
a 
medication. Obsessive-compulsive and related disorder due to another medical 
condition 
involves symptoms characteristic of obsessive-compulsive and related disorders that 
are the 



direct pathophysiological consequence of another medical condition. 


Other specified obsessive-compulsive and related disorder (e.g., nail 
biting, lip biting, cheek 
chewing, obsessional 
jealousy, olfactory reference disorder [olfactory reference syndrome]) and 
unspecified obsessive-compulsive and related disorder consist 
of symptoms that 
cause clinically 
significant 
distress or impairment 
that 
do not 
meet 
criteria for a specific obsessive-compulsive 
and related disorder in DSM-5 because of atypical 
presentation or uncertain etiology. These 
categories are also used for other specific syndromes that 
are not 
listed in Section II and when 
insufficient 
information is available to diagnose the presentation as another obsessive-
compulsive and related disorder. 


Those obsessive-compulsive and related disorders that 
have a cognitive component 
(i.e., 
OCD, body dysmorphic disorder, and hoarding disorder) include a specifier for 


265 


indicating the individual s degree of insight 
with respect 
to disorder-related beliefs, which 
ranges from 
 good or fair insight  to  poor insight  to  absent 
insight/delusional 
beliefs.  Those 
individuals whose degree of insight 
is in the  absent 
insight/delusional 
beliefs  range should not 
be given an additional 
diagnosis of a psychotic disorder unless their delusional 
beliefs involve 
content 
that 
extends beyond what 
is characteristic of their obsessive-compulsive and related 
disorder (e.g., an individual 
with body dysmorphic disorder who is convinced that 
his or her food 
has been poisoned). 


Obsessive-Compulsive Disorder 


Diagnostic Criteria 
F42.2 


A. 
Presence 
of 
obsessions, 
compulsions, 
or both: 
Obsessions are 
defined 
by (1) and 
(2): 
1. 
Recurrent 
and 
persistent 
thoughts, 
urges, 
or images that 
are 
experienced, 
at 
some 
time 
during 
the 
disturbance, 
as intrusive 
and 
unwanted, 
and 
that 
in 
most 
individuals cause 
marked 
anxiety or distress. 
2. 
The 
individual attempts to 
ignore 
or suppress such 
thoughts, 
urges, 
or 
images, 
or to 
neutralize 
them with 
some 
other thought 
or action 
(i.e., 
by 
performing 
a 
compulsion). 
Compulsions are 
defined 
by (1) and 
(2): 


1. 
Repetitive 
behaviors (e.g., 
hand 
washing, 
ordering, 
checking) or mental acts 
(e.g., 
praying, 
counting, 
repeating 
words silently) that 
the 
individual feels 
driven 
to 
perform in 
response 
to 
an 
obsession 
or according 
to 
rules that 
must 
be 
applied 
rigidly. 
2. 
The 
behaviors or mental acts are 
aimed 
at 
preventing 
or reducing 
anxiety or 
distress, 
or preventing 
some 
dreaded 
event 
or situation; 
however, 
these 

behaviors or mental acts are 
not 
connected 
in 
a 
realistic way with 
what 
they 


are 
designed 
to 
neutralize 
or prevent, 
or are 
clearly excessive. 
Note: 
Young 
children 
may not 
be 
able 
to 
articulate 
the 
aims of 
these 
behaviors or mental acts. 


B. 
The 
obsessions or compulsions are 
time-consuming 
(e.g., 
take 
more 
than 
1 
hour 
per day) or cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
C. 
The 
obsessive-compulsive 
symptoms are 
not 
attributable 
to 
the 
physiological 
effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical 
condition. 
D. 
The 
disturbance 
is not 
better explained 
by the 
symptoms of 
another mental 
disorder (e.g., 
excessive 
worries, 
as in 
generalized 
anxiety disorder; 
preoccupation 
with 
appearance, 
as in 
body dysmorphic disorder; 
difficulty 
discarding 
or parting 
with 
possessions, 
as in 
hoarding 
disorder; 
hair pulling, 
as in 
trichotillomania 
[hair-pulling 
disorder]; 
skin 
picking, 
as in 
excoriation 
[skinpicking] 
disorder; 
stereotypies, 
as in 
stereotypic movement 
disorder; 
ritualized 
eating 
behavior, 
as in 
eating 
disorders; 
preoccupation 
with 
substances or 
gambling, 
as in 
substance-related 
and 
addictive 
disorders; 
preoccupation 
with 
having 
an 
illness, 
as in 
illness anxiety disorder; 
sexual urges or fantasies, 
as in 
paraphilic disorders; 
impulses, 
as in 
disruptive, 
impulse-control, 
and 
conduct 
disorders; 
guilty ruminations, 
as in 
major depressive 
disorder; 
thought 
insertion 
or delusional preoccupations, 
as in 
schizophrenia 
spectrum and 
other psychotic 
disorders; 
or repetitive 
patterns of 
behavior, 
as in 
autism spectrum disorder). 
266 


Specify 
if: 
With 
good 
or fair insight: 
The 
individual recognizes that 
obsessive-compulsive 


disorder beliefs are 
definitely or probably not 
true 
or that 
they may or may not 
be 
true. 
With 
poor insight: 
The 
individual thinks obsessive-compulsive 
disorder beliefs 


are 
probably true. 
With 
absent insight/delusional 
beliefs: 
The 
individual is completely convinced 
that 
obsessive-compulsive 
disorder beliefs are 
true. 
Specify 
if: 
Tic-related: 
The 
individual has a 
current 
or past 
history of 
a 
tic disorder. 


Specifiers 


Individuals with obsessive-compulsive disorder (OCD) vary in the degree of insight 
they have 
about 
the accuracy of the beliefs that 
underlie their obsessive-compulsive symptoms. Many 
individuals have good or fair insight 
(e.g., the individual 
believes that 
the house definitely will 
not, probably will 
not, or may or may not 
burn down if the stove is not 
checked 30 times). Some 



have poor insight 
(e.g., the individual 
believes that 
the house will 
probably burn down if the 
stove is not 
checked 30 times), and a few (4% or less) have absent 
insight/delusional 
beliefs 
(e.g., the individual 
is convinced that 
the house will 
burn down if the stove is not 
checked 30 
times). Insight 
can vary within an individual 
over the course of the illness. Poorer insight 
has 
been linked to worse long-term outcome. 


Up to 30% of individuals with OCD have a lifetime tic disorder. This is most 
common in 
men with onset 
of OCD in childhood. These individuals tend to differ from 
those without 
a 
history of tic disorders in the themes of their OCD symptoms, comorbidity, course, and pattern 
of familial transmission. 


Diagnostic Features 


The characteristic symptoms of OCD are the presence of obsessions and compulsions (Criterion 
A). Obsessions 
are repetitive and persistent 
thoughts (e.g., of contamination), images (e.g., of 
violent 
or horrific scenes), or urges (e.g., to stab someone). Importantly, obsessions are not 
pleasurable or experienced as voluntary: 
they are intrusive and unwanted and cause marked 
distress or anxiety in most 
individuals. The individual 
attempts to ignore or suppress these 
obsessions (e.g., avoiding triggers or using thought 
suppression) or to neutralize them 
with 
another thought 
or action (e.g., performing a compulsion). Compulsions 
(or rituals) are repetitive 
behaviors (e.g., washing, checking) or mental 
acts (e.g., counting, repeating words silently) that 
the individual 
feels driven to perform 
in response to an obsession or according to rules that 
must 
be applied rigidly. Most 
individuals with OCD have both obsessions and compulsions. 
Obsessions and compulsions are typically thematically related (e.g., thoughts of contamination 
associated with washing rituals; 
thoughts of harm 
associated with repeated checking). 
Individuals often report 
that 
they perform 
compulsions to reduce the distress triggered by 
obsessions or to prevent 
a feared event 
(e.g., becoming ill). However, these compulsions either 
are not 
connected in a realistic way to the feared event 
(e.g., arranging items symmetrically to 
prevent 
harm 
to a loved one) or are clearly excessive (e.g., showering for hours each day). 
Compulsions are not 
done for pleasure, although individuals may experience temporary relief 
from anxiety or distress. 


The specific content 
of obsessions and compulsions varies between individuals. However, 
certain themes, or dimensions, are common, including those of cleaning (contamination 
obsessions and cleaning compulsions); 
symmetry (symmetry obsessions and repeating, ordering, 
and counting compulsions); 
forbidden or taboo thoughts (e.g., aggressive, sexual, or religious 
obsessions and related compulsions); 
and harm 
(e.g., fears of harm 
to self or others and checking 
compulsions). Some individuals also have difficulties discarding and accumulate objects as a 
consequence of typical obsessions and 


267 


compulsions (e.g., fears of harming others); 
such compulsions must 
be distinguished from 
the primary accumulation behaviors seen in hoarding disorder, discussed later in this chapter. 
These themes occur across different cultures, are relatively consistent over time in adults with the 
disorder, and may be associated with different 
neural 
substrates. Importantly, individuals often 
have symptoms in more than one dimension. 



Criterion B 
emphasizes that 
obsessions and compulsions must 
be time-consuming (e.g., more 
than 1 hour per day) or cause clinically significant 
distress or impairment 
to warrant 
a diagnosis 
of OCD. This criterion helps to distinguish the disorder from 
the occasional 
intrusive thoughts or 
repetitive behaviors that 
are common in the general 
population (e.g., double-checking that 
a door 
is locked). The frequency and severity of obsessions and compulsions vary across individuals 
with OCD (e.g., some have mild to moderate symptoms, spending 1 3 hours per day obsessing 
or doing compulsions, whereas others have nearly constant 
intrusive thoughts or compulsions 
that can be incapacitating). 


Associated Features 


Sensory phenomena, defined as physical 
experiences (e.g., physical 
sensations, just-right 
sensations, and feelings of incompleteness) that 
precede compulsions, are common in OCD. Up 
to 60% of individuals with OCD report these phenomena. 


Individuals with OCD experience a range of affective responses when confronted with 
situations that 
trigger obsessions and compulsions. For example, many individuals experience 
marked anxiety that 
can include recurrent 
panic attacks. Others report 
strong feelings of disgust. 
While performing compulsions, some individuals report 
a distressing sense of  incompleteness  
or uneasiness until things look, feel, or sound  just right.  


It 
is common for individuals with the disorder to avoid people, places, and things that 
trigger 
obsessions and compulsions. For example, individuals with contamination concerns might 
avoid 
public situations (e.g., restaurants, public restrooms) to reduce exposure to feared contaminants; 
individuals with intrusive thoughts about causing harm might avoid social interactions. 


Many individuals with OCD have dysfunctional 
beliefs. These beliefs can include an inflated 
sense of responsibility and the tendency to overestimate threat; 
perfectionism 
and intolerance of 
uncertainty; 
and overimportance of thoughts (e.g., believing that 
having a forbidden thought 
is as 
bad as acting on it) and the need to control 
thoughts. These beliefs, however, are not 
specific to 
OCD. The involvement 
of family or friends in compulsive rituals, termed accommodation, can 
exacerbate or maintain symptoms and is an important target in treatment, especially in children. 


Prevalence 


The 12-month prevalence of OCD in the United States is 1.2%, with a similar prevalence 
internationally (including Canada, Puerto Rico, Germany, Taiwan, Korea, and New Zealand; 
1.1% 1.8%). Women are affected at 
a slightly higher rate than men in adulthood, although men 
are more commonly affected in childhood. 


Development and Course 


In the United States, the mean age at 
onset 
of OCD is 19.5 years, and 25% of cases start 
by age 
14 years. Onset 
after age 35 years is unusual 
but 
does occur. Men have an earlier age at 
onset 
than women: 
nearly 25% of men have onset 
before age 10 years. The onset 
of symptoms is 
typically gradual; however, acute onset can also occur. 


If OCD is untreated, the course is usually chronic, often with waxing and waning symptoms. 
Some individuals have an episodic course, and a minority have a deteriorating course. Without 
treatment, remission rates in adults are low (e.g., 20% for those reevaluated 40 years later). Onset 



in childhood or adolescence can lead to a lifetime of OCD. 


268 


However, 40% of individuals with onset 
of OCD in childhood or adolescence may 
experience remission by early adulthood. The course of OCD is often complicated by the co-
occurrence of other disorders (see section  Comorbidity  for this disorder). 


Compulsions are more easily diagnosed in children than obsessions are because compulsions 
are usually observable. However, most 
children have both obsessions and compulsions (as do 
most 
adults). The pattern of symptoms in adults can be stable over time, but 
it 
is more variable in 
children. Some differences in the content 
of obsessions and compulsions have been reported 
when children and adolescent 
samples are compared with adult 
samples. These differences likely 
reflect 
content 
appropriate to different 
developmental 
stages (e.g., higher rates of sexual 
and 
religious obsessions in adolescents than in children; 
higher rates of harm 
obsessions [e.g., fears 
of catastrophic events, such as death or illness to self or loved ones] in children and adolescents 
than in adults). 


Risk and Prognostic Factors 


Temperamental. 
Greater internalizing symptoms, higher negative emotionality, and behavioral 


inhibition in childhood are possible temperamental risk factors. 
Environmental. 
Different 
environmental 
factors may increase the risk for OCD. These include 
adverse perinatal 
events, premature birth, maternal 
tobacco use during pregnancy, physical 
and 
sexual 
abuse in childhood, and other stressful 
or traumatic events. Some children may develop 
the sudden onset 
of obsessive-compulsive symptoms, which has been associated with different 
environmental 
factors, including various infectious agents and a postinfectious autoimmune 
syndrome. 


Genetic 
and 
physiological. 
The rate of OCD among first-degree relatives of adults with OCD is 
approximately two times that 
among first-degree relatives of those without 
the disorder; 
however, among first-degree relatives of individuals with onset 
of OCD in childhood or 
adolescence, the rate is increased 10-fold. Familial 
transmission is due in part 
to genetic factors 
(e.g., a concordance rate of 0.57 for monozygotic vs. 0.22 for dizygotic twins). Twin studies 
suggest 
that 
additive genetic effects account 
for ~40% of the variance in obsessive-compulsive 
symptoms. Dysfunction in the orbitofrontal 
cortex, anterior cingulate cortex, and striatum 
have 
been most 
strongly implicated; 
alterations in frontolimbic, frontoparietal, and cerebellar 
networks have also been reported. 


Culture-Related Diagnostic Issues 


OCD occurs across the world. There is substantial 
similarity across cultures in the gender 
distribution, age at 
onset, and comorbidity of OCD. Moreover, around the globe, there is a 
similar symptom 
structure involving cleaning, symmetry, hoarding, taboo thoughts, and fear of 
harm. However, regional 
variation in symptom 
expression exists, and cultural 
factors may shape 
the content 
of obsessions and compulsions. For example, obsessions related to sexual 
content 
may be reported less frequently in some religious and cultural 
groups, and obsessions related to 
violence and aggression may be more common in settings with higher prevalence of urban 



violence. Attributions of OCD symptoms vary cross-culturally, including physical, social, 
spiritual, and supernatural 
causes; 
specific compulsions and help-seeking options may be 
reinforced by these cultural attributions. 


Sex- and Gender-Related Diagnostic Issues 


Men have an earlier age at 
onset 
of OCD than women, often in childhood, and are more likely to 
have comorbid tic disorders. Onset 
in girls is more typically in adolescence; 
among adults, OCD 
is slightly more common in women than in men. Gender differences in the pattern of symptom 
dimensions have been reported, with, for example, women more likely to have symptoms in the 
cleaning dimension and men more likely to have 


269 


symptoms in the forbidden thoughts and symmetry dimensions. Onset 
or exacerbation of OCD, 
as well 
as symptoms that 
can interfere with the mother-infant 
relationship (e.g., aggressive 
obsessions such as intrusive violent 
thoughts of harming the infant, leading to avoidance of the 
infant), has been reported in the peripartum 
period. Some women also report 
exacerbation of 
OCD symptoms premenstrually. 


Association With Suicidal 
Thoughts or Behavior 


A systematic literature review of suicidal 
ideation and suicide attempts in clinical 
samples with 
OCD from 
multiple countries found a mean rate of lifetime suicide attempts of 14.2%, a mean 
rate of lifetime suicidal 
ideation of 44.1%, and a mean rate of current 
suicidal 
ideation of 25.9%. 
Predictors of greater suicide risk were severity of OCD, the symptom 
dimension of unacceptable 
thoughts, severity of comorbid depressive and anxiety symptoms, and past 
history of suicidality. 
Another international 
systematic review of 48 studies found a moderate to high significant 
association between suicidal ideation/suicide attempts and OCD. 


A cross-sectional 
study of 582 outpatients with OCD from 
Brazil 
found that 
36% reported 
lifetime suicidal 
thoughts, 20% had made suicide plans, 11% had already attempted suicide, and 
10% presented with current 
suicidal 
thoughts. The sexual/religious dimension of OCD and 
comorbid substance use disorders were associated with suicidal 
thoughts and suicide plans, 
impulse-control 
disorders were associated with current 
suicidal 
thoughts and with suicide plans 
and attempts, and lifetime comorbid major depressive disorder and posttraumatic stress disorder 
(PTSD) were associated with all aspects of suicidal behaviors. 


In a study using Swedish national 
registry data involving 36,788 individuals with OCD and 
matched general 
population control 
subjects, individuals with OCD had a higher risk of suicide 
death (OR = 9.8) and suicide attempt 
(OR = 5.5), and the increased risk for both outcomes 
remained substantial 
even after adjusting for psychiatric comorbidities. Comorbid personality or 
substance use disorder increased suicide risk, whereas female gender, higher parental 
education, 
and a comorbid anxiety disorder were protective factors. 


Functional 
Consequences of Obsessive-Compulsive Disorder 


OCD is associated with reduced quality of life as well 
as high levels of social 
and occupational 
impairment. Impairment 
occurs across many different 
domains of life and is associated with 



symptom 
severity. Impairment 
can be caused by the time spent 
obsessing and performing 
compulsions. Avoidance of situations that 
can trigger obsessions or compulsions can also 
severely impair functioning. In addition, specific symptoms can create specific obstacles. For 
example, obsessions about 
harm 
can make relationships with family and friends feel 
hazardous; 
the result 
can be avoidance of these relationships. Obsessions about 
symmetry can derail 
the 
timely completion of school 
or work projects because the project 
never feels  just 
right,  
potentially resulting in school 
failure or job loss. Health consequences can also occur. For 
example, individuals with contamination concerns may avoid doctors  offices and hospitals (e.g., 
because of fears of exposure to germs) or develop dermatological 
problems (e.g., skin lesions 
due to excessive washing). Sometimes the symptoms of the disorder interfere with its own 
treatment 
(e.g., when medications are considered contaminated). When the disorder starts in 
childhood or adolescence, individuals may experience developmental 
difficulties. For example, 
adolescents may avoid socializing with peers; 
young adults may struggle when they leave home 
to live independently. The result 
can be few significant 
relationships outside the family and a 
lack of autonomy and financial 
independence from 
their family of origin. In addition, some 
individuals with OCD try to impose rules and prohibitions on family members because of their 
obsessions 


270 


(e.g., no one in the family can have visitors to the house for fear of contamination), and this can 
lead to family dysfunction. 


Differential 
Diagnosis 


Anxiety 
disorders. 
Recurrent 
thoughts, avoidant 
behaviors, and repetitive requests for reassurance 
can also occur in anxiety disorders. However, the recurrent 
thoughts that 
are present 
in 
generalized anxiety disorder (i.e., worries) are usually about 
real-life concerns, whereas the 
obsessions of OCD usually do not 
involve real-life concerns and 
can include content 
that 
is odd, 
irrational, or of a seemingly magical 
nature; 
moreover, compulsions are usually present 
and 
usually linked to the obsessions. Like individuals with OCD, individuals with specific phobia 
can have a fear reaction to specific objects or situations; 
however, in specific phobia the feared 
object 
is usually much more circumscribed, and rituals are not 
present. In social 
anxiety disorder, 
the feared objects or situations are limited to social 
interactions or performance situations, and 
avoidance or reassurance seeking is focused on reducing feelings of embarrassment. 


Major depressive 
disorder. 
OCD needs to be distinguished from 
the rumination of major 
depressive disorder, in which thoughts are usually mood-congruent 
and not 
necessarily 
experienced as intrusive or distressing; 
moreover, ruminations are not 
linked to compulsions, as 
is typical in OCD. 
Other obsessive-compulsive 
and 
related 
disorders. 
In body dysmorphic disorder, the obsessions and 


compulsions are limited to concerns about 
physical 
appearance; 
and in trichotillomania (hairpulling 
disorder), the compulsive behavior is limited to hair pulling in the absence of obsessions. 
Hoarding disorder symptoms focus exclusively on the persistent 
difficulty discarding or parting 
with possessions, marked distress associated with discarding items, and excessive accumulation 
of objects. However, if an individual has obsessions that are typical of OCD (e.g., concerns about 



incompleteness or harm), and these obsessions lead to compulsive accumulation (e.g., acquiring 
all 
objects in a set 
to attain a sense of completeness or not 
discarding old newspapers because 
they may contain information that 
could prevent 
harm), a diagnosis of OCD should be given 
instead. 


Eating 
disorders. 
OCD can be distinguished from 
anorexia nervosa in that 
in OCD the obsessions 
and compulsions are not limited to concerns about weight and food. 
Tics 
(in 
tic 
disorder) 
and 
stereotyped 
movements. 
A tic 
is a sudden, rapid, recurrent, nonrhythmic 


motor movement 
or vocalization (e.g., eye blinking, throat 
clearing). A stereotyped movement 
is 
a repetitive, seemingly driven, nonfunctional 
motor behavior (e.g., head banging, body rocking, 
self-biting). Tics and stereotyped movements are typically less complex than compulsions and 
are not 
aimed at 
neutralizing obsessions. However, distinguishing between complex tics and 
compulsions can be difficult. Whereas compulsions are usually preceded by obsessions, tics are 
often preceded by premonitory sensory urges. Some individuals have symptoms of both OCD 
and a tic disorder, in which case both diagnoses may be warranted. 


Psychotic 
disorders. 
Some individuals with OCD have poor insight 
or even delusional 
OCD 
beliefs. However, they have obsessions and compulsions (distinguishing their condition from 
delusional 
disorder) and do not 
have other features of schizophrenia or schizoaffective disorder 
(e.g., hallucinations or disorganized speech). For individuals whose OCD symptoms warrant 
the 
 with absent 
insight/delusional 
beliefs  specifier, these symptoms should not 
be diagnosed as a 
psychotic disorder. 


Other compulsive-like 
behaviors. 
Certain behaviors are sometimes described as  compulsive,  
including sexual 
behavior (in the case of paraphilias), gambling (i.e., gambling disorder), and 
substance use (e.g., alcohol use disorder). However, these behaviors differ 


271 


from 
the compulsions of OCD in that 
the person usually derives pleasure from 
the activity and 


may wish to resist it only because of its deleterious consequences. 
Obsessive-compulsive 
personality 
disorder. 
Although obsessive-compulsive personality disorder 
and OCD have similar names, the clinical 
manifestations of these disorders are quite different. 
Obsessive-compulsive personality disorder is not 
characterized by intrusive thoughts, images, or 
urges or by repetitive behaviors that 
are performed in response to these intrusive symptoms; 
instead, it 
involves an enduring and pervasive maladaptive pattern of excessive perfectionism 
and rigid control. If an individual 
manifests symptoms of both OCD and obsessive-compulsive 
personality disorder, both diagnoses can be given. 


Comorbidity 


Individuals with OCD often have other psychopathology. Many adults with the disorder in the 
United States have a lifetime diagnosis of an anxiety disorder (76%; 
e.g., panic disorder, social 
anxiety disorder, generalized anxiety disorder, specific phobia) or a depressive or bipolar 
disorder (63% for any depressive or bipolar disorder, with the most 
common being major 
depressive disorder [41%]); 
a lifetime diagnosis of an impulse-control 
disorder (56%) or a 
substance use disorder (39%) is also common. Onset 
of OCD 
is usually later than for most 



comorbid anxiety disorders (with the exception of separation anxiety disorder) and PTSD but 
often precedes that 
of depressive disorders. In a study of 214 treatment-seeking adults in the 
United States with DSM-IV OCD at 
intake, comorbid obsessive-compulsive personality disorder 
was found in 23% 32% of individuals followed longitudinally. 


Up to 30% of individuals with OCD also have a lifetime tic disorder. A comorbid tic disorder 
is most 
common in men with onset 
of OCD in childhood. These individuals tend to differ from 
those without 
a history of tic disorders in the themes of their OCD symptoms, comorbidity, 
course, and pattern of familial 
transmission. A triad of OCD, tic disorder, and attentiondeficit/
hyperactivity disorder can also be seen in children. 


Several 
obsessive-compulsive and related disorders, including body dysmorphic disorder, 
trichotillomania, and excoriation (skin-picking) disorder, also occur more frequently in 
individuals with OCD than in those without OCD. 


OCD is also much more common in individuals with certain other disorders than would be 
expected based on its prevalence in the general 
population; 
when one of those other disorders is 
diagnosed, the individual 
should be assessed for OCD as well. For example, in individuals with 
schizophrenia or schizoaffective disorder, the prevalence of OCD is approximately 12%. Rates 
of OCD are also elevated in bipolar disorder; 
eating disorders, such as anorexia nervosa and 
bulimia nervosa; body dysmorphic disorder; and Tourette s disorder. 


Body Dysmorphic Disorder 


Diagnostic Criteria 
F45.22 


A. 
Preoccupation 
with 
one 
or more 
perceived 
defects or flaws in 
physical 
appearance 
that 
are 
not 
observable 
or appear slight 
to 
others. 
B. 
At 
some 
point 
during 
the 
course 
of 
the 
disorder, 
the 
individual has performed 
repetitive 
behaviors (e.g., 
mirror checking, 
excessive 
grooming, 
skin 
picking, 
reassurance 
seeking) or mental acts (e.g., 
comparing 
his or her appearance 
with 
that 
of 
others) in 
response 
to 
the 
appearance 
concerns. 
C. 
The 
preoccupation 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
272 


D. 
The 
appearance 
preoccupation 
is not 
better explained 
by concerns with 
body fat 
or weight 
in 
an 
individual whose 
symptoms meet 
diagnostic criteria 
for an 
eating 
disorder. 
Specify 
if: 
With 
muscle 
dysmorphia: 
The 
individual is preoccupied 
with 
the 
idea 
that 
his 
or her body build 
is too 
small or insufficiently muscular. 
This specifier is used 
even 
if 
the 
individual is preoccupied 
with 
other body areas, 
which 
is often 
the 
case. 



Specify 
if: 
Indicate 
degree 
of 
insight 
regarding 
body dysmorphic disorder beliefs (e.g., 
 I 
look 
ugly  or  I 
look deformed ). 
With 
good 
or fair insight: 
The 
individual recognizes that 
the 
body dysmorphic 


disorder beliefs are 
definitely or probably not 
true 
or that 
they may or may not 
be 
true. 
With 
poor insight: 
The 
individual thinks that 
the 
body dysmorphic disorder 


beliefs are 
probably true. 
With 
absent insight/delusional 
beliefs: 
The 
individual is completely convinced 
that 
the 
body dysmorphic disorder beliefs are 
true. 


Specifiers 


Muscle dysmorphia, a form 
of body dysmorphic disorder occurring almost 
exclusively in men 
and adolescent 
boys, consists of preoccupation with the idea that 
one s body is too small 
or 
insufficiently lean or muscular. Individuals with this form 
of the disorder actually have a normal-
looking body or are even very muscular. They may also be preoccupied with other body areas, 
such as skin or hair. A majority (but 
not 
all) diet, exercise, and/or lift 
weights excessively, 
sometimes causing bodily damage. Some use potentially dangerous anabolic-androgenic steroids 
and other substances to try to make their body bigger and more muscular. 


Individuals with body dysmorphic disorder vary in the degree of insight 
they have about 
the 
accuracy of their body dysmorphic disorder beliefs (e.g.,  I look ugly,   I look deformed ). 
Insight 
regarding body dysmorphic disorder beliefs can range from 
good to absent/delusional 
(i.e., delusional 
beliefs consisting of complete conviction that 
the individual s view of his or her 
appearance is accurate and undistorted). On average, insight 
is poor, and one-third or more of 
individuals currently have absent 
insight/delusional 
body dysmorphic disorder beliefs. 
Individuals with delusional 
body dysmorphic disorder tend to have greater morbidity in some 
areas (e.g., suicidal 
thoughts or behavior), but 
this appears to be accounted for by their tendency 
to have more severe body dysmorphic disorder symptoms. 


Diagnostic Features 


Individuals with body dysmorphic disorder (formerly known as dysmorphophobia) are 
preoccupied with one or more perceived defects or flaws in their physical 
appearance, which 
they believe look ugly, unattractive, abnormal, or deformed (Criterion A). The perceived flaws 
are not 
observable or appear only slight 
to other individuals. Concerns range from 
looking 
 unattractive  or  not 
right  to looking  hideous  or  like a monster.  Preoccupations can focus 
on one or many body areas, most 
commonly the skin (e.g., perceived acne, scars, lines, wrinkles, 
paleness), hair (e.g.,  thinning  hair or  excessive  body or facial 
hair), or nose (e.g., size or 
shape). However, any body area can be the focus of concern (e.g., eyes, teeth, weight, stomach, 
breasts, legs, face size or shape, lips, chin, eyebrows, genitals). Some individuals are concerned 
about 
perceived asymmetry of body areas. The preoccupations are intrusive, unwanted, time-
consuming (occurring, on average, 3 8 hours per day), and usually difficult to resist or control. 


Excessive repetitive behaviors or mental 
acts (e.g., comparing) are performed in response to 



the preoccupation (Criterion B). The individual feels driven to perform these 


273 


behaviors, which are not 
pleasurable and may increase anxiety and dysphoria. They are 
typically time-consuming and difficult 
to resist 
or control. Common behaviors are comparing 
one s appearance with that 
of other individuals; 
repeatedly checking perceived defects in mirrors 
or other reflecting surfaces or examining them 
directly; 
taking excessive  selfies ; 
excessively 
grooming (e.g., combing, styling, shaving, plucking or pulling hair); 
seeking reassurance about 
how the perceived flaws look; 
touching disliked areas to check them; 
excessively exercising or 
weight 
lifting; 
and seeking cosmetic procedures. Some individuals excessively tan (e.g., to 
darken  pale  skin or diminish perceived acne), repeatedly change their clothes (e.g., to 
camouflage perceived defects), or compulsively shop (e.g., for beauty products). Compulsive 
skin picking intended to improve perceived skin defects is common and can cause skin damage, 
infections, or ruptured blood vessels. Camouflaging (i.e., hiding or covering) perceived defects, a 
very common behavior in individuals with body dysmorphic disorder, may involve repetitive 
behaviors (e.g., repeatedly applying makeup, adjusting a hat 
or clothing, rearranging head hair to 
cover the forehead or eyes). The preoccupation must 
cause clinically significant 
distress or 
impairment 
in social, occupational, or other important 
areas of functioning (Criterion C); 
usually 
both are present. Body dysmorphic disorder must 
be differentiated from 
an eating disorder. Body 
dysmorphic disorder by proxy is a form 
of body dysmorphic disorder in which individuals are 
preoccupied with defects they perceive in another person s appearance, most 
often a significant 
other (e.g., spouse or partner), but sometimes a parent, child, sibling, or stranger. 


Associated Features 


Many individuals with body dysmorphic disorder have ideas or delusions of reference, believing 
that 
other people take special 
notice of them 
or mock them 
because of how they look. Body 
dysmorphic disorder is associated with high levels of anxiety, social 
anxiety, social 
avoidance, 
depressed mood, negative affectivity (neuroticism), rejection sensitivity, and perfectionism 
as 
well 
as low extroversion and low self-esteem. Body dysmorphic disorder is also associated with 
elevated hostility and aggressive behavior. Many individuals are ashamed of their appearance 
and their excessive focus on how they look and are reluctant 
to reveal 
their concerns to others. A 
majority of individuals receive cosmetic treatment 
to try to improve their perceived defects. 
Dermatological 
treatment 
and surgery are most 
common, but 
any type (e.g., dental, electrolysis) 
may be received. Some individuals perform 
surgery on themselves. Body dysmorphic disorder 
appears to respond poorly to such treatments and sometimes becomes worse. Some individuals 
take legal 
action or are violent 
toward the clinician (e.g., surgeon) because they are dissatisfied 
with the cosmetic outcome. 


Body dysmorphic disorder has been associated with abnormalities in emotion recognition, 
attention, and executive function, as well 
as information-processing biases and inaccuracies in 
interpretation of information and social 
situations. For example, individuals with this disorder 
tend to have a bias for negative and threatening interpretations of facial 
expressions and 
ambiguous scenarios. Body dysmorphic disorder is also characterized by visual 
processing 
abnormalities, with a bias for analyzing and encoding details rather than holistic or configural 



aspects of visual stimuli. 


Prevalence 


The point 
prevalence in a nationwide epidemiological 
study among U.S. adults was 2.4% (2.5% 
in women and 2.2% in men). Outside the United States (e.g., Germany), similar studies indicate 
that 
the point 
prevalence is 1.7% 2.9%, with a gender distribution similar to that 
in the United 
States. Globally, the point 
prevalence is 11% 13% among dermatology patients, 13% 15% 
among general 
cosmetic surgery patients, 20% in rhinoplasty surgery patients, 11% among adult 
jaw correction surgery patients, and 5% 10% among adult 
orthodontia/cosmetic dentistry 
patients. Among adolescents and college students, point 
prevalence rates are relatively higher in 
girls/young women compared with boys/young men. 


274 


Development and Course 


The mean age at 
disorder onset 
is 16 17 years, the median age at 
onset 
is 15 years, and the most 
common age at 
onset 
is 12 13 years; 
in two-thirds of individuals, onset 
is before age 18. 
Subclinical 
body dysmorphic disorder symptoms begin, on average, at 
age 12 or 13 years. 
Subclinical 
concerns usually evolve gradually to the full 
disorder, although some individuals 
experience abrupt 
onset 
of body dysmorphic disorder. The disorder appears to usually be 
chronic, although improvement 
is likely when evidence-based treatment 
is received. The 
disorder s clinical 
features appear largely similar in children/adolescents and adults. Body 
dysmorphic disorder occurs in the elderly, but 
little is known about 
the disorder in this age 
group. Individuals with disorder onset 
before age 18 years have more comorbidity and are more 
likely to have gradual 
(rather than acute) disorder onset 
than those with adult-onset 
body 
dysmorphic disorder. 


Risk and Prognostic Factors 


Environmental. 
Body dysmorphic disorder has been associated with high rates of childhood 


neglect, abuse, and trauma, as well as elevated rates of teasing. 
Genetic 
and 
physiological. 
The prevalence of body dysmorphic disorder is elevated in first-degree 
relatives of individuals with obsessive-compulsive disorder (OCD). Heritability of body 
dysmorphic disorder symptoms is estimated at 
37% 49% in studies of adolescent 
and young 
adult 
twins and may be higher in women. There is shared genetic vulnerability with OCD as well 
as genetic influences that are specific to body dysmorphic disorder symptoms. 


Culture-Related Diagnostic Issues 


Body dysmorphic disorder has been reported internationally. Certain features of the disorder 
appear cross-culturally, such as gender ratio, body areas that 
are the object 
of concern, types of 
repetitive behaviors, and levels of associated distress and impairment. Other features may vary 
(e.g., in some cultural 
contexts with a collectivistic focus, such as Japan, body dysmorphic 
concerns might emphasize the fear of offending others because of the perceived deformity). 


Varying cultural 
standards may be associated with specific body image concerns, such as 



eyelids in Japan and muscle dysmorphia in Western countries. Taijin kyofusho, 
included in the 
traditional 
Japanese diagnostic system, has a subtype similar to body dysmorphic disorder: 
shubo-kyofu 
( the phobia of a deformed body ). For more information regarding cultural 
concepts of distress, refer to the  Culture and Psychiatric Diagnosis  chapter. 


Sex- and Gender-Related Diagnostic Issues 


Muscle dysmorphia occurs almost 
exclusively in men, and men are more likely to have a 
comorbid substance use disorder, whereas women are more likely to have a comorbid eating 
disorder. Women and men appear to have more similarities than differences in terms of most 
clinical 
features  for example, disliked body areas, types of repetitive behaviors, symptom 
severity, suicidality, comorbidity, illness course, and receipt 
of cosmetic procedures for body 
dysmorphic disorder. However, there are some differences. For example, men are more likely to 
have preoccupations with their genitals, body build (thinking they are too small 
or inadequately 
muscular), and thinning hair, whereas women are more likely to be preoccupied with weight 
(usually thinking that 
they weigh too much), breasts/chest, buttocks, legs, hips, and excessive 
body/facial hair. 


Association With Suicidal 
Thoughts or Behavior 


In a systematic review and meta-analysis of 17 studies that 
examined suicidal 
thoughts and 
behaviors across several countries, individuals with body dysmorphic disorder were 


275 


four times more likely to have experienced suicidal 
thoughts (pooled OR = 3.87) and 2.6 times 
more likely to have made suicide attempts (pooled OR = 2.57) when compared with healthy 
control 
subjects and individuals diagnosed with eating disorders, OCD, or any anxiety disorder. 
Two general 
population studies in Germany found higher rates of suicidal 
thoughts 19% vs. 
3%; 
31.0% vs. 3.5% and behaviors 7% vs. 1%; 
22.2% vs. 2.1% in individuals diagnosed 
with body dysmorphic disorder than in those without the diagnosis. 


Severity of body dysmorphic disorder strengthens the association of body dysmorphic 
disorder with suicidal 
thoughts and behaviors. The relationship between body dysmorphic 
disorder and elevated suicidal 
thoughts and behaviors is independent 
of comorbidity, but 
certain 
comorbidities may further strengthen this relationship. A substantial 
proportion of individuals 
with body dysmorphic disorder attribute suicidal 
thoughts or suicide attempts primarily to their 
appearance concerns. 


Individuals with body dysmorphic disorder have many demographic and clinical 
risk factors 
that 
more generally predict 
suicide death, such as high rates of suicidal 
thoughts and suicide 
attempts, unemployment, perceived abuse, poor self-esteem, and high rates of comorbid major 
depressive disorder, eating disorders, and substance use disorders. 


Functional 
Consequences of Body Dysmorphic Disorder 


Nearly all 
individuals with body dysmorphic disorder experience impaired psychosocial 
functioning because of their appearance concerns. Impairment 
can range from 
moderate (e.g., 
avoidance of some social 
situations) to extreme and incapacitating (e.g., being completely 



housebound). 


On average, psychosocial 
functioning and quality of life are markedly poor. More severe 
body dysmorphic disorder symptoms are associated with poorer functioning and quality of life. 
Most 
individuals experience impairment 
in their job, academic, or role functioning (e.g., as a 
parent 
or caregiver), which is often severe (e.g., performing poorly, missing school 
or work, not 
working). About 
20% of youths with body dysmorphic disorder report 
dropping out 
of school 
primarily because of their body dysmorphic disorder symptoms. A high proportion of adults and 
adolescents have been psychiatrically hospitalized. 


Differential 
Diagnosis 


Normal 
appearance 
concerns 
and 
clearly 
noticeable 
physical 
defects. 
Body dysmorphic disorder 
differs from 
normal 
appearance concerns in being characterized by excessive appearance-related 
preoccupations and repetitive behaviors that 
are time-consuming, are usually difficult 
to resist 
or 
control, and cause clinically significant 
distress or impairment 
in functioning. Physical 
defects 
that 
are clearly noticeable (i.e., not 
slight) are not 
diagnosed as body dysmorphic disorder. 


However, skin picking as a symptom 
of body dysmorphic disorder can cause noticeable skin 
lesions and scarring; in such cases, body dysmorphic disorder should be diagnosed. 
Eating 
disorders. 
In an individual 
with an eating disorder, concerns about 
being fat 
or overweight 


are considered a symptom 
of the eating disorder rather than body dysmorphic disorder. However, 
weight 
concerns may occur in body dysmorphic disorder. Eating disorders and body dysmorphic 
disorder can be comorbid, in which case both should be diagnosed. 
Other obsessive-compulsive 
and 
related 
disorders. 
The preoccupations and repetitive behaviors of 


body dysmorphic disorder differ from 
obsessions and compulsions in OCD in that 
the former 
focus only on physical 
appearance. These disorders have other differences, such as poorer 
insight, more frequent depression, and higher rates of suicidal 


276 


ideation in body dysmorphic disorder. When skin picking is intended to improve the appearance 
of perceived skin defects, body dysmorphic disorder, rather than excoriation (skin-picking) 
disorder, is diagnosed. When hair removal 
(plucking, pulling, or other types of removal) is 
intended to improve perceived defects in the appearance of facial, head, or body hair, body 
dysmorphic disorder is diagnosed rather than trichotillomania (hair-pulling disorder). 


Illness 
anxiety 
disorder. 
Individuals with body dysmorphic disorder are not 
preoccupied with 
having or acquiring a serious illness and in clinical 
samples do not 
have particularly elevated 
levels of somatization. 


Major depressive 
disorder. 
The prominent 
preoccupation with appearance and excessive repetitive 
behaviors in body dysmorphic disorder differentiate it 
from 
major depressive disorder. However, 
major depressive disorder and depressive symptoms are common in individuals with body 
dysmorphic disorder, often appearing to be secondary to the distress and impairment 
that 
body 
dysmorphic disorder causes. Body dysmorphic disorder should be diagnosed in depressed 
individuals if diagnostic criteria for body dysmorphic disorder are met. 


Anxiety 
disorders. 
Social 
anxiety and avoidance are common in body dysmorphic disorder. 



However, unlike social 
anxiety disorder, agoraphobia, and avoidant 
personality disorder, body 
dysmorphic disorder includes prominent 
appearance-related preoccupation, which may be 
delusional, and repetitive behaviors. In addition, the social 
anxiety and avoidance that 
are 
characteristic of body dysmorphic disorder are attributable to concerns about 
perceived 
appearance defects and the belief or fear that 
other people will 
consider these individuals ugly, 
ridicule them, or reject 
them 
because of their physical 
features. Unlike generalized anxiety 
disorder, anxiety and worry in body dysmorphic disorder focus on perceived appearance flaws. 


Psychotic 
disorders. 
Many individuals with body dysmorphic disorder have delusional 
appearance beliefs (i.e., complete conviction that 
their view of their perceived defects is 
accurate), which is diagnosed as body dysmorphic disorder, with absent 
insight/delusional 
beliefs, not 
as delusional 
disorder. Appearance-related ideas or delusions of reference are 
common in body dysmorphic disorder (i.e., thinking that 
other people take special 
notice in a 
negative way because of the individual s appearance). However, unlike schizophrenia or 
schizoaffective disorder, body dysmorphic disorder involves prominent 
appearance 
preoccupations and related repetitive behaviors; 
disorganized behavior and other psychotic 
symptoms are absent 
(except 
for appearance beliefs, which may be delusional). For individuals 
whose obsessive-compulsive and related disorder symptoms warrant 
the  with absent 
insight/delusional 
beliefs  specifier, these symptoms should not 
be diagnosed as a psychotic 
disorder. 


Other disorders 
and 
symptoms. 
Body dysmorphic disorder should not 
be diagnosed if the 
preoccupation is limited to discomfort 
with or a desire to be rid of one s primary and/or 
secondary sex characteristics in an individual 
with gender dysphoria. Nor should body 
dysmorphic disorder be diagnosed if the preoccupation focuses on the belief that 
one emits a foul 
or offensive body odor as in olfactory reference disorder (olfactory reference syndrome), which 
is an example of an other specified obsessive-compulsive and related disorder in DSM-5. Body 
integrity dysphoria 
(which is included in ICD-11 but 
not 
DSM-5) involves a persistent 
desire to 
become an amputee in order to correct 
a mismatch between the individual s sense of how his or 
her body should be configured and his or her actual 
anatomical 
configuration. In contrast 
to body 
dysmorphic disorder, the individual 
does not 
feel 
that 
the limb to be amputated is ugly or 
defective in any way, just 
that 
it 
should not 
be there. Koro, 
a culturally related disorder that 
usually occurs in epidemics in Southeastern Asia, consists of a fear that 
the penis (labia, nipples, 
or breasts in females) is shrinking or retracting and will 
disappear into the abdomen, often 
accompanied by a belief that death 


277 


will 
result. Koro 
differs from 
body dysmorphic disorder in several 
ways, including a focus on 
death rather than preoccupation with perceived ugliness. Dysmorphic concern 
(which is not 
a 
DSM-5 disorder) is a broader construct 
that 
is similar to, but 
not 
equivalent 
to, body dysmorphic 
disorder. It 
involves symptoms reflecting an overconcern with slight 
or imagined flaws in 
appearance. 


Comorbidity 


Major depressive disorder is the most 
common comorbid disorder, with onset 
usually after that 



of body dysmorphic disorder. Comorbid social 
anxiety disorder, OCD, and substance-related 
disorders (including use of anabolic-androgenic steroids in the muscle dysmorphia form 
of body 
dysmorphic disorder) are also common. 


Hoarding 
Disorder 


Diagnostic Criteria 
F42.3 


A. 
Persistent 
difficulty discarding 
or parting 
with 
possessions, 
regardless of 
their 
actual value. 
B. 
This difficulty is due 
to 
a 
perceived 
need 
to 
save 
the 
items and 
to 
distress 
associated 
with 
discarding 
them. 
C. 
The 
difficulty discarding 
possessions results in 
the 
accumulation 
of 
possessions 
that 
congest 
and 
clutter active 
living 
areas and 
substantially compromises their 
intended 
use. 
If 
living 
areas are 
uncluttered, 
it 
is only because 
of 
the 
interventions of 
third 
parties (e.g., 
family members, 
cleaners, 
authorities). 
D. 
The 
hoarding 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
(including 
maintaining 
a 
safe 
environment 
for self 
and 
others). 
E. 
The 
hoarding 
is not 
attributable 
to 
another medical condition 
(e.g., 
brain 
injury, 
cerebrovascular disease, 
Prader-Willi syndrome). 
F. 
The 
hoarding 
is not 
better explained 
by the 
symptoms of 
another mental disorder 
(e.g., 
obsessions in 
obsessive-compulsive 
disorder, 
decreased 
energy in 
major 
depressive 
disorder, 
delusions in 
schizophrenia 
or another psychotic disorder, 
cognitive 
deficits in 
major neurocognitive 
disorder, 
restricted 
interests in 
autism 
spectrum disorder). 
Specify 
if: 
With 
excessive 
acquisition: 
If 
difficulty discarding 
possessions is accompanied 
by excessive 
acquisition 
of 
items that 
are 
not 
needed 
or for which 
there 
is no 
available 
space. 
Specify 
if: 
With 
good 
or fair insight: 
The 
individual recognizes that 
hoarding-related 


beliefs and 
behaviors (pertaining 
to 
difficulty discarding 
items, 
clutter, 
or 
excessive 
acquisition) are 
problematic. 
With 
poor insight: 
The 
individual is mostly convinced 
that 
hoarding-related 


beliefs and 
behaviors (pertaining 
to 
difficulty discarding 
items, 
clutter, 
or 


excessive 
acquisition) are 
not 
problematic despite 
evidence 
to 
the 
contrary. 
With 
absent insight/delusional 
beliefs: 
The 
individual is completely convinced 
that 
hoarding-related 
beliefs and 
behaviors (pertaining 
to 
difficulty discarding 
items, 
clutter, 
or excessive 
acquisition) are 
not 
problematic despite 
evidence 
to 
the 
contrary. 



278 


Specifiers 


With 
excessive 
acquisition. 
Approximately 80% 90% of individuals with hoarding disorder 
display excessive acquisition. The most 
frequent 
form 
of acquisition is excessive buying, 
followed by acquisition of free items (e.g., leaflets, items discarded by others). Stealing is less 
common. Some individuals may deny excessive acquisition when first 
assessed, yet 
it 
may 
appear later during the course of treatment. Individuals with hoarding disorder typically 
experience distress if they are unable to or are prevented from acquiring items. 


Diagnostic Features 


The essential 
feature of hoarding disorder is persistent 
difficulty discarding or parting with 
possessions, regardless of their actual 
value (Criterion A). The term 
persistent 
indicates a longstanding 
difficulty rather than more transient 
life circumstances that 
may lead to excessive 
clutter, such as inheriting property. The difficulty in discarding possessions noted in Criterion A 
refers to any form 
of discarding, including throwing away, selling, giving away, or recycling. 
The main reasons given for this difficulty are the perceived utility or aesthetic value of the items 
or strong sentimental 
attachment 
to the possessions. Some individuals feel 
responsible for the 
fate of their possessions and often go to great 
lengths to avoid being wasteful. Fears of losing 
important 
information are also common. The most 
commonly saved items are newspapers, 
magazines, clothing, bags, books, mail, and papers, but 
virtually any item 
can be saved. The 
nature of items is not 
limited to possessions that 
most 
other people would define as useless or of 
limited value. Many individuals collect 
and save large numbers of valuable things as well, which 
are often found in piles mixed with other less valuable items. 


Individuals with hoarding disorder purposefully save possessions and experience distress 
(e.g., anxiety, frustration, regret, sadness, guilt) when facing the prospect 
of discarding them 
(Criterion B). This criterion emphasizes that 
the saving of possessions is intentional, which 
discriminates hoarding disorder from 
other forms of psychopathology that 
are characterized by 
the passive accumulation of items or the absence of distress when possessions are removed. 


Individuals accumulate large numbers of items that 
fill 
up and clutter active living areas to 
the extent 
that 
their intended use is no longer possible (Criterion C). For example, the individual 
may not 
be able to cook in the kitchen, sleep in his or her bed, or sit 
in a chair. If the space can 
be used, it 
is only with great 
difficulty. Clutter 
is defined as a large group of usually unrelated or 
marginally related objects piled together in a disorganized fashion in spaces designed for other 
purposes (e.g., tabletops, floor, hallway). Criterion C 
emphasizes the  active  living areas of the 
home, rather than more peripheral areas, such as garages, attics, or basements, that are sometimes 
cluttered in homes of individuals without 
hoarding disorder. However, individuals with hoarding 
disorder often have possessions that 
spill 
beyond the active living areas and can occupy and 
impair the use of other spaces, such as vehicles, yards, the workplace, and friends  and relatives  
houses. In some cases, living areas may be uncluttered only because of the intervention of third 
parties (e.g., family members, cleaners, local 
authorities). Individuals who have been forced to 
clear their homes still 
have a symptom 
picture that 
meets criteria for hoarding disorder because 



the lack of clutter is attributable to a third-party intervention. Hoarding disorder contrasts with 
normative collecting behavior, which is organized and selective, although in some cases the 
actual 
amount 
of possessions may be similar to the amount 
accumulated by an individual 
with 
hoarding disorder. Normative collecting does not 
produce the clutter, distress, or impairment 
typical of hoarding disorder. 


Symptoms (i.e., difficulty discarding and/or clutter) must 
cause clinically significant 
distress 
or impairment 
in social, occupational, or other important 
areas of functioning, including 
maintaining a safe environment 
for self and others (Criterion D). In some cases, particularly 
when there is poor insight, the individual may not report distress, and the 


279 


impairment 
may be apparent 
only to those around the individual. However, any attempts to 
discard or clear the possessions by third parties result in high levels of distress. 


Associated Features 


Other common features of hoarding disorder include indecisiveness, perfectionism, avoidance, 
procrastination, difficulty planning and organizing tasks, and distractibility. Some individuals 
with hoarding disorder live in unsanitary conditions that 
may be a logical 
consequence of 
severely cluttered spaces and/or that 
are related to planning and organizing difficulties. Animal 
hoarding 
can be defined as the accumulation of a large number of animals and a failure to 
provide minimal 
standards of nutrition, sanitation, and veterinary care, as well 
as failure to act 
on 
the deteriorating condition of the animals (including disease, starvation, or death) and the 
environment 
(e.g., severe overcrowding, extremely unsanitary conditions). Animal 
hoarding may 
be a special 
manifestation of hoarding disorder. Many individuals who hoard animals also hoard 
inanimate objects. The most 
prominent 
differences between animal 
and object 
hoarding are the 
extent of unsanitary conditions and the poorer insight in animal hoarding. 


Prevalence 


Nationally representative prevalence studies of hoarding disorder are not 
available. Community 
surveys estimate the point 
prevalence of clinically significant 
hoarding in the United States and 
Europe to range between 1.5% and 6%. In a meta-analysis of 12 studies across high-income 
countries, a prevalence of 2.5% was found, with no gender difference identified. This contrasts 
with clinical 
samples, which are predominantly women. In one population-based study in the 
Netherlands, hoarding symptoms appeared to be almost 
three times more prevalent 
in older 
adults (older than 65 years) compared with younger adults (ages 30 40 years). 


Development and Course 


Hoarding appears to begin early in life and spans well 
into the late stages. Hoarding symptoms 
may first 
emerge around ages 15 19 years, start 
interfering with the individual s everyday 
functioning by the mid-20s, and cause clinically significant 
impairment 
by the mid-30s. 
Participants in clinical 
research studies are usually in their 50s. Thus, the severity of hoarding 
increases with each decade of life, especially after age 30. Once symptoms begin, the course of 
hoarding is often chronic, with few individuals reporting a waxing and waning course. 



Pathological 
hoarding in children appears to be easily distinguished from 
developmentally 
adaptive saving and collecting behaviors. Because children and adolescents typically do not 
control 
their living environment 
and discarding behaviors, the possible intervention of third 
parties (e.g., parents keeping the spaces usable and thus reducing interference) should be 
considered when making the diagnosis. 


Risk and Prognostic Factors 


Temperamental. 
Indecisiveness is a prominent 
feature of individuals with hoarding disorder and 


their first-degree relatives. 
Environmental. 
Individuals with hoarding disorder often retrospectively report 
stressful 
and 
traumatic life events preceding the onset of the disorder or causing an exacerbation. 


Genetic 
and 
physiological. 
Hoarding behavior is familial; more than 50% of individuals who hoard 
report 
having a relative who also hoards. Twin studies indicate that 
approximately 50% of the 
variability in hoarding behavior is attributable to additive genetic factors and the rest 
to 
nonshared environmental factors. 


280 


Culture-Related Diagnostic Issues 


While most 
of the research has been done in Western, industrialized countries and urban 
communities, the available data from 
low- and middle-income countries suggest 
that 
hoarding 
has consistent 
clinical 
features cross-culturally, including similarities in severity at 
clinical 
presentation and associated cognitions and behaviors. In cultural 
contexts in which a high value 
is placed on thrift 
and storing of possessions, the presence of distress and functional 
impairment 
should be the basis for the diagnosis. 


Sex- and Gender-Related Diagnostic Issues 


The key features of hoarding disorder (i.e., difficulty discarding, excessive amount 
of clutter) are 
generally comparable in men and women, but 
women tend to display more excessive acquisition, 
particularly excessive buying, than do men. 


Functional 
Consequences of Hoarding Disorder 


Clutter impairs basic activities, such as moving through the house, cooking, cleaning, 
maintaining personal 
hygiene, and even sleeping. Appliances may be broken, and utilities such 
as water and electricity may be disconnected, as access for repair work may be difficult. Quality 
of life is often considerably impaired. In severe cases, hoarding can put 
individuals at 
risk for 
fire, falling (especially elderly individuals), poor sanitation, and other health risks. Hoarding 
disorder is associated with occupational 
impairment, poor physical 
health, and high social 
service utilization. Family relationships are frequently under great 
strain. Conflict 
with neighbors 
and local 
authorities is common, and a substantial 
proportion of individuals with severe hoarding 
disorder have been involved in legal eviction proceedings, and some have a history of eviction. 


Differential 
Diagnosis 



Other medical 
conditions. 
Hoarding disorder is not 
diagnosed if the symptoms are judged to be a 
direct 
consequence of another medical 
condition (Criterion E), such as traumatic brain injury, 
surgical 
resection for treatment 
of a tumor or seizure control, cerebrovascular disease, infections 
of the central 
nervous system 
(e.g., herpes simplex encephalitis), or neurogenetic conditions such 
as Prader-Willi 
syndrome. Damage to the anterior ventromedial 
prefrontal 
and cingulate cortices 
has been particularly associated with the excessive accumulation of objects. In these individuals, 
the hoarding behavior is not 
present 
prior to the onset 
of the brain damage and appears shortly 
after the brain damage occurs. Some of these individuals appear to have little interest 
in the 
accumulated items and are able to discard them 
easily or do not 
care if others discard them, 
whereas others appear to be very reluctant to discard anything. 


Neurodevelopmental 
disorders. 
Hoarding disorder is not 
diagnosed if the accumulation of objects 
is judged to be a direct 
consequence of a neurodevelopmental 
disorder, such as autism 
spectrum 
disorder or intellectual developmental disorder (intellectual disability). 
Schizophrenia 
spectrum and 
other psychotic 
disorders. 
Hoarding disorder is not 
diagnosed if the 


accumulation of objects is judged to be a direct 
consequence of delusions or negative symptoms 


in schizophrenia spectrum and other psychotic disorders. 
Major depressive 
episode. 
Hoarding disorder is not 
diagnosed if the accumulation of objects is 
judged to be a direct 
consequence of psychomotor retardation, fatigue, or loss of energy during a 
major depressive episode. 


Obsessive-compulsive 
disorder. 
Hoarding disorder is not 
diagnosed if the symptoms are judged to 
be a direct 
consequence of typical 
obsessions or compulsions, such as fears of contamination, 
harm, or feelings of incompleteness in obsessive-compulsive disorder 


281 


(OCD). Feelings of incompleteness (e.g., losing one s identity, or having to document 
and 
preserve all 
life experiences) are the most 
frequent 
OCD symptoms associated with this form 
of 
hoarding. The accumulation of objects can also be the result 
of persistently avoiding onerous 
rituals (e.g., not discarding objects in order to avoid endless washing or checking rituals). 


In OCD, the behavior is generally unwanted and highly distressing, and the individual 
experiences no pleasure or reward from 
it. Excessive acquisition is usually not 
present; 
if 
excessive acquisition is present, items are acquired because of a specific obsession (e.g., the need 
to buy items that 
have been accidentally touched in order to avoid contaminating other people), 
not 
because of a genuine desire to possess the items. Individuals who hoard in the context 
of 
OCD are also more likely to accumulate bizarre items, such as trash, feces, urine, fingernail 
and 
toenail 
cuttings, hair, used diapers, or rotten food. Accumulation of such items is very unusual 
in 
hoarding disorder. 


When severe hoarding appears concurrently with other typical 
symptoms of OCD but 
is 
judged to be independent 
from 
these symptoms, both hoarding disorder and OCD may be 
diagnosed. 


Neurocognitive 
disorders. 
Hoarding disorder is not 
diagnosed if the accumulation of objects is 
judged to be a direct 
consequence of a degenerative disorder, such as neurocognitive disorder 
associated with frontotemporal 
degeneration or Alzheimer s disease. Typically, onset 
of the 
accumulating behavior is gradual 
and follows onset 
of the neurocognitive disorder. The 



accumulating behavior may be accompanied by self-neglect 
and severe domestic squalor, 
alongside other neuropsychiatric symptoms, such as disinhibition, gambling, rituals/stereotypies, 
tics, and self-injurious behaviors. 


Comorbidity 


Approximately 75% of individuals with hoarding disorder have a comorbid mood or anxiety 
disorder. The most 
common comorbid conditions are major depressive disorder (30% 50%), 
social 
anxiety disorder, and generalized anxiety disorder. Approximately 20% of individuals 
with hoarding disorder also have symptoms that 
meet 
diagnostic criteria for OCD. These 
comorbidities may often be the main reason for consultation, because individuals are unlikely to 
spontaneously report 
hoarding symptoms, and hoarding symptoms are often not 
asked about 
in 
routine clinical interviews. 


Trichotillomania (Hair-Pulling 
Disorder) 


Diagnostic Criteria 
F63.3 


A. 
Recurrent 
pulling 
out 
of 
one s hair, 
resulting 
in 
hair loss. 
B. 
Repeated 
attempts to 
decrease 
or stop 
hair pulling. 
C. 
The 
hair pulling 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
D. 
The 
hair pulling 
or hair loss is not 
attributable 
to 
another medical condition 
(e.g., 
a 
dermatological condition). 
E. 
The 
hair pulling 
is not 
better explained 
by the 
symptoms of 
another mental 
disorder (e.g., 
attempts to 
improve 
a 
perceived 
defect 
or flaw in 
appearance 
in 
body dysmorphic disorder). 
Diagnostic Features 


The essential 
feature of trichotillomania (hair-pulling disorder) is the recurrent 
pulling out 
of 
one s own hair (Criterion A). Hair pulling may occur from any region of the body in 


282 


which hair grows; 
the most 
common sites are the scalp, eyebrows, and eyelids, while less 
common sites are axillary, facial, pubic, and perirectal 
regions. Hair-pulling sites may vary over 
time. Hair pulling may occur in brief episodes scattered throughout 
the day or during less 
frequent 
but 
more sustained periods that 
can continue for hours, and such hair pulling may 
endure for months or years. Criterion A requires that 
hair pulling lead to hair loss, although 
individuals with this disorder may pull 
hair in a widely distributed pattern (i.e., pulling single 
hairs from 
all 
over a site) such that 
hair loss may not 
be clearly visible. In addition, individuals 
may attempt 
to conceal 
or camouflage hair loss (e.g., by using makeup, scarves, or wigs). 



Individuals with trichotillomania have made repeated attempts to decrease or stop hair pulling 
(Criterion B). Criterion C 
indicates that 
hair pulling causes clinically significant 
distress or 
impairment 
in social, occupational, or other important 
areas of functioning. The term 
distress 
includes negative affects that 
may be experienced by individuals with hair pulling, such as 
feeling a loss of control, embarrassment, and shame. Significant 
impairment 
may occur in 
several 
different 
areas of functioning (e.g., social, occupational, academic, and leisure), in part 
because of avoidance of work, school, or other public situations. 


Associated Features 


Hair pulling may be accompanied by a range of behaviors or rituals involving hair. Thus, 
individuals may search for a particular kind of hair to pull 
(e.g., hairs with a specific texture or 
color), may try to pull 
out 
hair in a specific way (e.g., so that 
the root 
comes out 
intact), or may 
visually examine or tactilely or orally manipulate the hair after it has been pulled (e.g., rolling the 
hair between the fingers, pulling the strand between the teeth, biting the hair into pieces, or 
swallowing the hair). 


Hair pulling may also be preceded or accompanied by various emotional 
states; 
it 
may be 
triggered by feelings of anxiety or boredom, may be preceded by an increasing sense of tension 
(either immediately before pulling out 
the hair or when attempting to resist 
the urge to pull), or 
may lead to gratification, pleasure, or a sense of relief when the hair is pulled out. Hair-pulling 
behavior may involve varying degrees of conscious awareness, with some individuals displaying 
more focused attention on the hair pulling (with preceding tension and subsequent 
relief), and 
other individuals displaying more automatic behavior (in which the hair pulling seems to occur 
without 
full 
awareness). Many individuals report 
a mix of both behavioral 
styles. Some 
individuals experience an  itch-like  or tingling sensation in the scalp that 
is alleviated by the act 
of pulling hair. Pain does not usually accompany hair pulling. 


Patterns of hair loss are highly variable. Areas of complete alopecia, as well 
as areas of 
thinned hair density, are common. When the scalp is involved, there may be a predilection for 
pulling out 
hair in the crown or parietal 
regions. There may be a pattern of nearly complete 
baldness except 
for a narrow perimeter around the outer margins of the scalp, particularly at 
the 
nape of the neck ( tonsure trichotillomania ). Eyebrows and eyelashes may be completely 
absent. 


Hair pulling does not 
usually occur in the presence of other individuals, except 
immediate 
family members. Some individuals have urges to pull 
hair from 
other individuals and may 
sometimes try to find opportunities to do so surreptitiously. Some individuals may pull 
hairs 
from 
pets, dolls, and other fibrous materials (e.g., sweaters or carpets). Some individuals may 
deny their hair pulling to others. The majority of individuals with trichotillomania also have one 
or more other body-focused repetitive behaviors, including skin picking, nail 
biting, and lip 
chewing. 


Prevalence 


In the general 
population, data from 
nonrepresentative U.S. samples have suggested that 
the 12month 
prevalence estimate for trichotillomania in adults and adolescents may be in 


283 



the range of 1% to 2%. Women are more frequently affected than men in self-identified or 
clinical 
samples, at 
a ratio estimated at 
10:1 or greater, but 
the gender ratio may be closer to 2:1 
in community samples. Among children with trichotillomania, boys and girls are more equally 
represented. An online survey of more than 10,000 adults ages 18 69 years, representative of the 
general 
U.S. population, found that 
1.7% identified as having current 
trichotillomania and that 
rates did not differ significantly based on gender (1.8% of men and 1.7% of women). 


Development and Course 


Hair pulling may be seen in infants, and this behavior typically resolves during early 
development. Onset of hair pulling in trichotillomania most commonly coincides with, or follows 
the onset 
of, puberty. Sites of hair pulling may vary over time. The usual 
course of 
trichotillomania is chronic, with some waxing and waning if the disorder is untreated. Symptoms 
may worsen in females premenstrually but 
not 
consistently during pregnancy. For some 
individuals, the disorder may come and go for weeks, months, or years at 
a time. A minority of 
individuals remit without subsequent relapse within a few years of onset. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
There is evidence for a genetic vulnerability to trichotillomania. The 
disorder is more common in individuals with obsessive-compulsive disorder (OCD) and their 
first-degree relatives than in the general population. 


Culture-Related Diagnostic Issues 


Trichotillomania appears to manifest 
similarly across cultures and ethnicities, although there is a 
paucity of data from non-Western regions. 


Diagnostic Markers 


Most 
individuals with trichotillomania admit 
to hair pulling; 
thus, dermatopathological 
diagnosis 
is rarely required. Skin biopsy and dermoscopy (or trichoscopy) of trichotillomania are able to 
differentiate the disorder from 
other causes of alopecia. In trichotillomania, dermoscopy shows a 
range of characteristic features, including decreased hair density, short 
vellus hair, and broken 
hairs with different shaft lengths. 


Functional 
Consequences of Trichotillomania (Hair-Pulling Disorder) 


Trichotillomania is associated with distress as well 
as with social 
and occupational 
impairment. 
There may be irreversible damage to hair growth and hair quality. Infrequent 
medical 
consequences of trichotillomania include digit 
purpura, musculoskeletal 
injury (e.g., carpal 
tunnel 
syndrome; 
back, shoulder and neck pain), blepharitis, and dental 
damage (e.g., worn or 
broken teeth resulting from 
hair biting). Swallowing of hair (trichophagia) may lead to 
trichobezoars, with subsequent 
anemia, abdominal 
pain, hematemesis, nausea and vomiting, 
bowel obstruction, and even bowel perforation. 


Differential 
Diagnosis 



Normative 
hair removal/manipulation. 
Trichotillomania should not 
be diagnosed when hair removal 
is performed solely for cosmetic reasons (i.e., to improve physical 
appearance). Many 
individuals twist 
and play with their hair, but 
this behavior does not 
usually qualify for a 
diagnosis of trichotillomania. Some individuals may bite rather than pull 
hair; 
again, this does 
not qualify for a diagnosis of trichotillomania. 


284 


Other obsessive-compulsive 
and 
related 
disorders. 
Individuals with OCD and symmetry concerns 
may pull 
out 
hairs as part 
of their symmetry rituals, and individuals with body dysmorphic 


disorder may remove body hair that 
they perceive as ugly, asymmetrical, or abnormal; 
in such 
cases a diagnosis of trichotillomania is not given. 
Stereotypic 
movement 
disorder. 
Stereotypic movement 
disorder can sometimes involve hair-

pulling behavior. For example, a child with intellectual 
developmental 
disorder (intellectual 
disability) or autism 
spectrum 
disorder may engage in stereotypic head banging, hand or arm 
biting, and hair pulling when frustrated or angry, and sometimes when excited. This behavior, if 
impairing, would be diagnosed as stereotypic movement 
disorder (co-occurring with intellectual 
developmental disorder or autism spectrum disorder) rather than trichotillomania. 


Psychotic 
disorder. 
Individuals with a psychotic disorder may remove hair in response to a 


delusion or hallucination. Trichotillomania is not diagnosed in such cases. 
Another medical 
condition. 
Trichotillomania is not 
diagnosed if the hair pulling or hair loss is 
attributable to another medical 
condition (e.g., inflammation of the skin or other dermatological 
conditions). Other causes of noncicatricial 
(nonscarring) alopecia (e.g., alopecia areata, 
androgenic alopecia, telogen effluvium) or cicatricial 
(scarring) (e.g., chronic discoid lupus 
erythematosus, lichen planopilaris, central 
centrifugal 
cicatricial 
alopecia, pseudopelade, 
folliculitis decalvans, dissecting folliculitis, acne keloidalis nuchae) should be considered in 
individuals with hair loss who deny hair pulling. Skin biopsy or dermoscopy can be used to 
differentiate individuals with trichotillomania from those with dermatological disorders. 


Substance-related 
disorders. 
Hair-pulling symptoms may be exacerbated by certain substances  
for example, stimulants but 
it 
is less likely that 
substances are the primary cause of persistent 
hair pulling. 


Comorbidity 


Trichotillomania is often accompanied by other mental 
disorders, most 
commonly major 
depressive disorder and excoriation (skin-picking) disorder. Repetitive body-focused symptoms 
other than hair pulling or skin picking (e.g., nail 
biting) occur in the majority of individuals with 
trichotillomania and may deserve an additional 
diagnosis of other specified obsessive-
compulsive and related disorder (i.e., other body-focused repetitive behavior disorder). 


Excoriation 
(Skin-Picking) Disorder 


F42.4Diagnostic Criteria

A. 
Recurrent 
skin 
picking 
resulting 
in 
skin 
lesions. 
B. 
Repeated 
attempts to 
decrease 
or stop 
skin 
picking. 
C. 
The 
skin 
picking 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
D. 
The 
skin 
picking 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
cocaine) or another medical condition 
(e.g., 
scabies). 
E. 
The 
skin 
picking 
is not 
better explained 
by symptoms of 
another mental disorder 
(e.g., 
delusions or tactile 
hallucinations in 
a 
psychotic disorder, 
attempts to 
improve 
a 
perceived 
defect 
or flaw in 
appearance 
in 
body dysmorphic disorder, 
stereotypies in 
stereotypic movement 
disorder, 
or intention 
to 
harm oneself 
in 
nonsuicidal self-injury). 
285 


Diagnostic Features 


The essential 
feature of excoriation (skin-picking) disorder is recurrent 
picking at 
one s own skin 
(Criterion A). The most 
commonly picked sites are the face, arms, and hands, but 
many 
individuals pick from 
multiple body sites. Individuals may pick at 
healthy skin, at 
minor skin 
irregularities, at 
lesions such as pimples or calluses, or at 
scabs from 
previous picking. Most 
individuals pick with their fingernails, although many use tweezers, pins, or other objects. In 
addition to skin picking, there may be skin rubbing, squeezing, lancing, and biting. Individuals 
with excoriation disorder often spend significant 
amounts of time on their picking behavior, 
sometimes several 
hours per day, and such skin picking may endure for months or years. 
Criterion A requires that 
skin picking lead to skin lesions, although individuals with this disorder 
often attempt 
to conceal 
or camouflage such lesions (e.g., with makeup or clothing). Individuals 
with excoriation disorder have made repeated attempts to decrease or stop skin picking (Criterion 
B). 


Criterion C 
indicates that 
skin picking causes clinically significant 
distress or impairment 
in 
social, occupational, or other important 
areas of functioning. The term 
distress 
includes negative 
affects that 
may be experienced by individuals with skin picking, such as feeling a loss of 
control, embarrassment, and shame. Significant 
impairment 
may occur in several 
different 
areas 
of functioning (e.g., social, occupational, academic, and leisure), in part 
because of avoidance of 
social situations. 


Associated Features 


Skin picking may be accompanied by a range of behaviors or rituals involving skin or scabs. 
Thus, individuals may search for a particular kind of scab to pull, and they may examine, play 
with, or mouth or swallow the skin after it 
has been pulled. Skin picking may also be preceded or 
accompanied by various emotional 
states. Skin picking may be triggered by feelings of anxiety 
or boredom, may be preceded by an increasing sense of tension (either immediately before 
picking the skin or when attempting to resist 
the urge to pick), and may lead to gratification, 
pleasure, or a sense of relief when the skin or scab has been picked. Some individuals report 



picking in response to a minor skin irregularity or to relieve an uncomfortable bodily sensation. 
Pain is not 
routinely reported to accompany skin picking. Some individuals engage in skin 
picking that 
is more focused (i.e., with preceding tension and subsequent 
relief), whereas others 
engage in more automatic picking (i.e., when skin picking occurs without 
preceding tension and 
without 
full 
awareness), and many have a mix of both behavioral 
styles. Skin picking does not 
usually occur in the presence of other individuals, except 
immediate family members. Some 
individuals report picking the skin of others. 


Prevalence 


An online survey of more than 10,000 adults, ages 18 69 years, age- and gender-matched to the 


U.S. population, found that 
2.1% identified as having current 
excoriation disorder and 3.1% 
reported lifetime excoriation disorder. Three-quarters or more of individuals with the disorder are 
women in community samples. 
Development and Course 


Although individuals with excoriation disorder may present 
at 
various ages, the skin picking 
most 
often has onset 
during adolescence, commonly coinciding with or following the onset 
of 
puberty. The disorder frequently begins with a dermatological 
condition, such as acne. Sites of 
skin picking may vary over time. The usual 
course is chronic, with some waxing and waning if 
untreated. For some individuals, the disorder may come and go for weeks, months, or years at 
a 
time. 


286 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
There is evidence for a genetic vulnerability to excoriation disorder. 
The disorder is more common in individuals with obsessive-compulsive disorder (OCD) and 
their first-degree family members than in the general population. 


Culture-Related Diagnostic Issues 


There are limited data on the prevalence and clinical 
characteristics of excoriation disorder 
across cultures. However, clinical 
features appear similar in studies of individuals in the United 
States and other countries. 


Diagnostic Markers 


Most 
individuals with excoriation disorder admit 
to skin picking; 
therefore, dermatopathological 
diagnosis is rarely required. However, the disorder may have characteristic features on 
histopathology. 


Functional 
Consequences of Excoriation (Skin-Picking) Disorder 


Excoriation disorder is associated with social 
and occupational 
impairment. The majority of 
individuals with this condition spend at 
least 
1 hour per day picking, thinking about 
picking, and 
resisting urges to pick. Many individuals report 
avoiding social 
or entertainment 
events as well 



as going out 
in public. A majority of individuals with the disorder also report 
experiencing work 
interference from 
skin picking on at 
least 
a daily or weekly basis. A significant 
proportion of 
students with excoriation disorder report 
having missed school, having experienced difficulties 
managing responsibilities at 
school, or having had difficulties studying because of skin picking. 
Medical 
complications of skin picking include tissue damage, scarring, and infection and can be 
life-threatening. Rarely, synovitis of the wrists resulting from 
chronic picking has been reported. 
Skin picking often results in significant 
tissue damage and scarring. It 
frequently requires 
antibiotic treatment for infection, and on occasion it may require surgery. 


Differential 
Diagnosis 


Psychotic 
disorder. 
Skin picking may occur in response to a delusion (i.e., parasitosis) or tactile 
hallucination (i.e., formication) in a psychotic disorder. In such cases, excoriation disorder 
should not be diagnosed. 
Other obsessive-compulsive 
and 
related 
disorders. 
Excessive washing compulsions in response to 


contamination obsessions in individuals with OCD may lead to skin lesions, and skin picking 
may occur in individuals with body dysmorphic disorder who pick their skin because of 
appearance concerns; 
in such cases, excoriation disorder should not 
be diagnosed. The 
description of other body-focused repetitive behavior disorder in other specified obsessive-
compulsive and related disorder excludes individuals whose symptoms meet 
diagnostic criteria 
for excoriation disorder. 


Neurodevelopmental 
disorders. 
While stereotypic movement 
disorder may be characterized by 
repetitive self-injurious behavior, onset 
is in the early developmental 
period. For example, 
individuals with the neurogenetic condition Prader-Willi 
syndrome may have early onset 
of skin 
picking, and their symptoms may meet 
criteria for stereotypic movement 
disorder. While tics in 
individuals with Tourette s disorder may lead to self-injury, the behavior is not 
tic-like in 
excoriation disorder. 


287 


Dermatitis 
artefacta. 
Dermatitis artefacta (also referred to as  factitious dermatitis ) is a term 
used 
in dermatology to refer to medically unexplained, presumably self-induced skin lesions that 
the 
individual 
denies any role in creating. Cases in which there is evidence of deception on the 
individual s part 
concerning the skin lesions can be diagnosed as either malingering (if the skin 
picking is motivated by external 
incentives) or factitious disorder (if the skin picking occurs in 
the absence of obvious external 
rewards). In the absence of deception, excoriation disorder can 
be diagnosed if there are repeated attempts to decrease or stop skin picking. 


Other disorders. 
Excoriation disorder is not 
diagnosed if the skin picking is primarily attributable 


to the intention to harm oneself that is characteristic of nonsuicidal self-injury. 
Other medical 
conditions. 
Excoriation disorder is not 
diagnosed if the skin picking is primarily 
attributable to another medical 
condition. For example, scabies is a dermatological 
condition 
invariably associated with severe itching and scratching. However, excoriation disorder may be 
precipitated or exacerbated by an underlying dermatological 
condition. For example, acne may 
lead to some scratching and picking, which may also be associated with comorbid excoriation 



disorder (so-called acne excori e). The differentiation between these two clinical 
situations (acne 
with some scratching and picking vs. acne with comorbid excoriation disorder) requires an 
assessment 
of the extent 
to which the individual s skin picking has become independent 
of the 
underlying dermatological condition. 


Substance/medication-induced 
disorders. 
Skin-picking symptoms may also be induced by certain 
substances (e.g., cocaine), in which case excoriation disorder should not 
be diagnosed. If such 
skin picking is clinically significant, then a diagnosis of substance/medication-induced 
obsessive-compulsive and related disorder should be considered. 


Comorbidity 


Excoriation disorder is often accompanied by other mental 
disorders. Such disorders include 
OCD and trichotillomania (hair-pulling disorder), as well 
as major depressive disorder. 
Depression comorbidity seems to be more common in women. Repetitive body-focused 
symptoms other than skin picking and hair pulling (e.g., nail 
biting) occur in many individuals 
with excoriation disorder and may deserve an additional 
diagnosis of other specified obsessive-
compulsive and related disorder (i.e., other body-focused repetitive behavior disorder). 


Substance/Medication-Induced 
Obsessive-Compulsive 
and 
Related 
Disorder 


Diagnostic Criteria 


A. 
Obsessions, 
compulsions, 
skin 
picking, 
hair pulling, 
other body-focused 
repetitive 
behaviors, 
or other symptoms characteristic of 
the 
obsessive-
compulsive 
and 
related 
disorders predominate 
in 
the 
clinical picture. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
of 
both 
(1) and 
(2): 
1. 
The 
symptoms in 
Criterion 
A 
developed 
during 
or soon 
after substance 
intoxication 
or withdrawal or after exposure 
to 
or withdrawal from a 
medication. 
2. 
The 
involved 
substance/medication 
is capable 
of 
producing 
the 
symptoms in 
Criterion 
A. 
288 


C. 
The 
disturbance 
is not 
better explained 
by an 
obsessive-compulsive 
and 
related 
disorder that 
is not 
substance/medication-induced. 
Such 
evidence 
of 
an 
independent 
obsessive-compulsive 
and 
related 
disorder could 
include 
the 
following: 
The 
symptoms precede 
the 
onset 
of 
the 
substance/medication 
use; 
the 
symptoms persist 
for a 
substantial period 
of 
time 
(e.g., 
about 
1 
month) after 



the 
cessation 
of 
acute 
withdrawal or severe 
intoxication; 
or there 
is other 
evidence 
suggesting 
the 
existence 
of 
an 
independent 
non-
substance/medication-induced 
obsessive-compulsive 
and 
related 
disorder 
(e.g., 
a 
history of 
recurrent 
non-substance/medication-related 
episodes). 


D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Note: 
This diagnosis should 
be 
made 
in 
addition 
to 
a 
diagnosis of 
substance 
intoxication 
or substance 
withdrawal only when 
the 
symptoms in 
Criterion 
A 
predominate 
in 
the 
clinical picture 
and 
are 
sufficiently severe 
to 
warrant 
clinical 
attention. 


Coding 
note: 
The 
ICD-10-CM codes for the 
[specific substance/medication]-induced 
obsessive-compulsive 
and 
related 
disorders are 
indicated 
in 
the 
table 
below. 
Note 
that 
the 
ICD-10-CM code 
depends on 
whether or not 
there 
is a 
comorbid 
substance 
use 
disorder present 
for the 
same 
class of 
substance. 
In 
any case, 
an 
additional 
separate 
diagnosis of 
a 
substance 
use 
disorder is not 
given. 
If 
a 
mild 
substance 
use 
disorder is comorbid 
with 
the 
substance-induced 
obsessive-compulsive 
and 
related 
disorder, 
the 
4th 
position 
character is  1,  and 
the 
clinician 
should 
record 
 mild 
[substance] 
use 
disorder  before 
the 
substance-induced 
obsessive-compulsive 
and 
related 
disorder (e.g., 
 mild 
cocaine 
use 
disorder with 
cocaine-induced 
obsessive-
compulsive 
and 
related 
disorder ). 
If 
a 
moderate 
or severe 
substance 
use 
disorder is 
comorbid 
with 
the 
substance-induced 
obsessive-compulsive 
and 
related 
disorder, 
the 
4th 
position 
character is  2,  and 
the 
clinician 
should 
record 
 moderate 
[substance] 
use 
disorder  or  severe 
[substance] 
use 
disorder,  depending 
on 
the 
severity of 
the 
comorbid 
substance 
use 
disorder. 
If 
there 
is no 
comorbid 
substance 
use 
disorder (e.g., 
after a 
one-time 
heavy use 
of 
the 
substance), 
then 
the 
4th 
position 
character is  9,  and 
the 
clinician 
should 
record 
only the 
substance-induced 
obsessive-compulsive 
and 
related 
disorder. 


ICD-10-CM 


With 
mild 
use 
With 
moderate 
or 
Without 
use 
disorder 
severe 
use 
disorder 
disorder 
Amphetamine-type 
substance 
(or 
other 
stimulant) 
F15.188 
F15.288 
F15.988 
Cocaine 
F14.188 
F14.288 
F14.988 
Other 
(or 
unknown) 
substance 
F19.188 
F19.288 
F19.988 


Specify 
(see 
Table 
1 
in 
the 
chapter  Substance-Related 
and 
Addictive 
Disorders,  
which 
indicates whether  with 
onset 
during 
intoxication  and/or  with 
onset 
during 
withdrawal  applies to 
a 
given 
substance 
class; 
or specify 
 with 
onset 
after 
medication 
use ): 


With 
onset during 
intoxication: 
If 
criteria 
are 
met 
for intoxication 
with 
the 
substance 
and 
the 
symptoms develop 
during 
intoxication. 



289 


With 
onset during 
withdrawal: 
If 
criteria 
are 
met 
for withdrawal from the 


substance 
and 
the 
symptoms develop 
during, 
or shortly after, 
withdrawal. 
With 
onset after medication 
use: 
If 
symptoms developed 
at 
initiation 
of 
medication, 
with 
a 
change 
in 
use 
of 
medication, 
or during 
withdrawal of 
medication. 


Recording Procedures 


The name of the substance/medication-induced obsessive-compulsive and related disorder begins 
with the specific substance (e.g., cocaine) that 
is presumed to be causing the obsessive-
compulsive and related symptoms. The diagnostic code is selected from 
the table included in the 
criteria set, which is based on the drug class and presence or absence of a comorbid substance 
use disorder. For substances that 
do not 
fit 
into any of the classes (e.g., ropinirole), the code for 
 other (or unknown) substance  should be used; 
and in cases in which a substance is judged to 
be an etiological 
factor but 
the specific class of substance is unknown, the same code should also 
be used. 


To record the name of the disorder, the comorbid substance use disorder (if any) is listed 
first, followed by  with substance/medication-induced obsessive-compulsive and related 
disorder  (incorporating the name of the specific etiological 
substance/medication), followed by 
the specification of onset 
(i.e., onset 
during intoxication, onset 
during withdrawal, with onset 
after medication use). For example, in the case of repetitive skin-picking occurring during 
intoxication in a man with a severe cocaine use disorder, the diagnosis is F14.288 severe cocaine 
use disorder with cocaine-induced obsessive-compulsive and related disorder, with onset 
during 
intoxication. A separate diagnosis of the comorbid severe cocaine use disorder is not 
given. If the 
substance-induced obsessive-compulsive and related disorder occurs without 
a comorbid 
substance use disorder (e.g., after a one-time heavy use of the substance), no accompanying 
substance use disorder is noted (e.g., F15.988 amphetamine-induced obsessive-compulsive and 
related disorder, with onset during intoxication). When more than one substance is judged to play 
a significant 
role in the development 
of the obsessive-compulsive and related disorder, each 
should be listed separately. 


Diagnostic Features 


The essential 
features of substance/medication-induced obsessive-compulsive and related 
disorder are prominent 
symptoms of an obsessive-compulsive and related disorder (Criterion A) 
that 
are judged to be attributable to the effects of a substance (e.g., drug of abuse, medication). 
The obsessive-compulsive and related disorder symptoms must 
have developed during or soon 
after substance intoxication or withdrawal 
or after exposure to or withdrawal 
from 
a medication 
or toxin, and the substance/medication must 
be capable of producing the symptoms (Criterion 
B). Substance/medication-induced obsessive-compulsive and related disorder due to a prescribed 
treatment 
for a mental 
disorder or other medical 
condition must 
have its onset 
while the 
individual 
is receiving the medication. Once the treatment 
is discontinued, the obsessive-
compulsive and related disorder symptoms will 
usually improve or remit 
within days to weeks 



(depending on the half-life of the substance/medication and the presence of withdrawal). The 
diagnosis of substance/medication-induced obsessive-compulsive and related disorder should not 
be given if onset 
of the obsessive-compulsive and related disorder symptoms precedes the 
substance/medication use, or if the symptoms persist 
for a substantial 
period of time, usually 
longer than 1 month, from 
the time of severe intoxication or withdrawal. The 
substance/medication-induced obsessive-compulsive and related disorder diagnosis should be 
made instead of a diagnosis of substance intoxication or substance withdrawal 
only when the 
symptoms in Criterion A predominate in the clinical 
picture and are sufficiently severe to 
warrant independent clinical attention. 


290 


Associated Features 


Obsessions, compulsions, hair pulling, skin picking, or other body-focused repetitive behaviors 
can occur in association with intoxication with the following classes of substances: 
stimulants 
(including cocaine) and other (or unknown) substances. Heavy metals and toxins may also cause 
obsessive-compulsive and related disorder symptoms. 


Prevalence 


In the U.S. general 
population, the very limited data that 
are available indicate that 
substance/medication-induced obsessive-compulsive and related disorder is very rare. 


Differential 
Diagnosis 


Substance 
intoxication 
and 
substance 
withdrawal. 
Obsessive-compulsive and related disorder 
symptoms may occur in the context 
of substance intoxication and substance withdrawal. The 
diagnosis of the substance-specific intoxication or substance-specific withdrawal 
will 
usually 
suffice to categorize the symptom 
presentation. A diagnosis of substance/medication-induced 
obsessive-compulsive and related disorder either with onset 
during intoxication or with onset 
during withdrawal 
should be made instead of a diagnosis of substance intoxication or substance 
withdrawal 
if the obsessive-compulsive and related disorder symptoms are judged to be in excess 
of those usually associated with intoxication or withdrawal 
and are sufficiently severe to warrant 


clinical attention. 
Obsessive-compulsive 
and 
related 
disorder (i.e., 
not 
induced 
by 
a 
substance). 
Substance/medicationinduced 
obsessive-compulsive and related disorder is distinguished from 
a primary obsessive-

compulsive and related disorder by considering the onset, course, and other factors with respect 
to substances/medications. For drugs of abuse, there must 
be evidence from 
the history, physical 
examination, or laboratory findings for use or intoxication. Substance/medication-induced 
obsessive-compulsive and related disorder arises only in association with intoxication, whereas a 
primary obsessive-compulsive and related disorder may precede the onset 
of 
substance/medication use. The presence of features that 
are atypical 
of a primary obsessive-
compulsive and related disorder, such as atypical 
age at 
onset 
of symptoms, may suggest 
a 
substance-induced etiology. A primary obsessive-compulsive and related disorder diagnosis is 
warranted if the symptoms persist 
for a substantial 
period of time (about 
1 month or longer) after 



the end of the substance intoxication or the individual 
has a history of an obsessive-compulsive 
and related disorder. 


Obsessive-compulsive 
and 
related 
disorder due 
to 
another medical 
condition. 


If the obsessive-
compulsive and related symptoms are attributable to another medical 
condition (i.e., rather than 
to the medication taken for the other medical 
condition), obsessive-compulsive and related 
disorder due to another medical 
condition should be diagnosed. The history often provides the 
basis for judgment. At 
times, a change in the treatment 
for the other medical 
condition (e.g., 
medication substitution or discontinuation) may be needed to determine whether the medication 
is the causative agent 
(in which case the symptoms may be better explained by 
substance/medication-induced obsessive-compulsive and related disorder). If the disturbance is 
attributable to both another medical 
condition and substance use, both diagnoses (i.e., obsessive-
compulsive and related disorder due to another medical 
condition and substance/medicationinduced 
obsessive-compulsive and related disorder) may be given. When there is insufficient 
evidence to determine whether the symptoms are attributable to a substance/medication or to 
another medical 
condition or are primary (i.e., attributable to neither a substance/medication nor 
another medical 
condition), a diagnosis of other specified or unspecified obsessive-compulsive 
and related disorder would be indicated. 


291 


Delirium. 
If obsessive-compulsive and related disorder symptoms occur exclusively during the 
course of delirium, they are considered to be an associated feature of the delirium 
and are not 
diagnosed separately. 


Obsessive-Compulsive and 
Related 
Disorder Due to 
Another Medical 
Condition 


Diagnostic Criteria 
F06.8 


A. 
Obsessions, 
compulsions, 
preoccupations with 
appearance, 
hoarding, 
skin 
picking, 
hair pulling, 
other body-focused 
repetitive 
behaviors, 
or other symptoms 
characteristic of 
obsessive-compulsive 
and 
related 
disorder predominate 
in 
the 
clinical picture. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
that 
the 
disturbance 
is the 
direct 
pathophysiological consequence 
of 
another 
medical condition. 
C. 
The 
disturbance 
is not 
better explained 
by another mental disorder. 
D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Specify 
if: 



With 
obsessive-compulsive 
disorder like 
symptoms: 
If 
obsessive-

compulsive 
disorder like 
symptoms predominate 
in 
the 
clinical presentation. 
With 
appearance 
preoccupations: 
If 
preoccupation 
with 
perceived 
appearance 
defects or flaws predominates in 
the 
clinical presentation. 


With 
hoarding 
symptoms: 
If 
hoarding 
predominates in 
the 
clinical presentation. 


With 
hair-pulling 
symptoms: 
If 
hair pulling 
predominates in 
the 
clinical 
presentation. 
With 
skin-picking 
symptoms: 
If 
skin 
picking 
predominates in 
the 
clinical 


presentation. 
Coding 
note: 
Include 
the 
name 
of 
the 
other medical condition 
in 
the 
name 
of 
the 
mental disorder (e.g., 
F06.8 
obsessive-compulsive 
and 
related 
disorder due 
to 
cerebral infarction). 
The 
other medical condition 
should 
be 
coded 
and 
listed 
separately immediately before 
the 
obsessive-compulsive 
and 
related 
disorder due 
to 
the 
medical condition 
(e.g., 
I69.398 
cerebral infarction; 
F06.8 
obsessive-
compulsive 
and 
related 
disorder due 
to 
cerebral infarction). 


Diagnostic Features 


The essential 
feature of obsessive-compulsive and related disorder due to another medical 
condition is clinically significant 
obsessive-compulsive and related symptoms that 
are judged to 
be best 
explained as the direct 
pathophysiological 
consequence of another medical 
condition. 
Symptoms can include prominent 
obsessions, compulsions, preoccupations with appearance, 
hoarding, hair pulling, skin picking, or other body-focused repetitive behaviors (Criterion A). 
The judgment 
that 
the symptoms are best 
explained by the associated medical 
condition must 
be 
based on evidence from 
the history, physical 
examination, or laboratory findings (Criterion B). 
Additionally, it 
must 
be judged that 
the symptoms are not 
better explained by another mental 
disorder (Criterion C). The diagnosis is not 
made if the obsessive-compulsive and related 
symptoms occur only during the course of a delirium 
(Criterion D). The obsessive-compulsive 
and related symptoms must 
cause clinically significant 
distress or impairment 
in social, 
occupational, or other important areas of functioning (Criterion E). 


292 


In determining whether the obsessive-compulsive and related symptoms are attributable to 
another medical 
condition, a medical 
condition must 
be present 
at 
the time of the onset 
of the 
obsessive-compulsive and related symptoms. Furthermore, it 
must 
be established that 
obsessive-
compulsive and related symptoms can be etiologically related to the medical 
condition through a 
pathophysiological 
mechanism 
and that 
this best 
explains the symptoms in the individual. 
Although there are no infallible guidelines for determining whether the relationship between the 
obsessive-compulsive and related symptoms and the medical 
condition is etiological, 
considerations that 
may provide some guidance in making this diagnosis include the presence of 
a clear temporal 
association between the onset, exacerbation, or remission of the medical 
condition and the obsessive-compulsive and related symptoms; 
the presence of features that 
are 
atypical 
of a primary obsessive-compulsive and related disorder (e.g., atypical 
age at 
onset 
or 



course); 
and evidence in the literature that 
a known physiological 
mechanism 
(e.g., striatal 
damage due to a cerebral 
infarction) causes obsessive-compulsive and related symptoms. In 
addition, the disturbance cannot 
be better explained by a primary obsessive-compulsive and 
related disorder, a substance/medication-induced obsessive-compulsive and related disorder, or 
another mental disorder. 


There has been considerable attention to the question of whether obsessive-compulsive and 
related disorders can be attributed to Group A streptococcal 
infection. Sydenham s chorea is the 
neurological 
manifestation of rheumatic fever, which is in turn due to Group A streptococcal 
infection. Sydenham s chorea is characterized by a combination of motor and nonmotor 
symptoms. Nonmotor features include obsessions, compulsions, attention deficit, and emotional 
lability. Although individuals with Sydenham s chorea may present 
with non-neuropsychiatric 
features of acute rheumatic fever, such as carditis and arthritis, they may present 
with obsessive-
compulsive disorder like symptoms; 
such individuals should be diagnosed with obsessive-
compulsive and related disorder due to another medical condition. 


Pediatric autoimmune neuropsychiatric disorders associated with streptococcal 
infections 
(PANDAS) has been identified as another postinfectious autoimmune disorder characterized by 
the sudden onset 
of obsessions, compulsions, and/or tics accompanied by a variety of acute 
neuropsychiatric symptoms in the absence of chorea, carditis, or arthritis, after Group A 
streptococcal 
infection. However, given that 
such acute-onset 
symptoms may be due to a range 
of other infections or insults, the term 
pediatric acute-onset 
neuropsychiatric syndrome 
(PANS) 
has been used. PANS 
is characterized by abrupt, dramatic onset 
of obsessive-compulsive 
symptoms or severely restricted food intake, together with a range of additional 
neuropsychiatric 
symptoms. Assessment guidelines for this syndrome are available. 


Associated Features 


A number of other medical 
conditions are known to include obsessive-compulsive and related 
symptoms as a manifestation. Examples include disorders leading to striatal 
damage, such as 
cerebral infarction or Huntington s disorder. 


Development and Course 


The development 
and course of obsessive-compulsive and related disorder due to another 
medical condition generally follows the course of the underlying illness. 


Diagnostic Markers 


Laboratory assessments and/or medical 
examinations are necessary to confirm 
the diagnosis of 
another medical condition. 


Differential 
Diagnosis 


Delirium. 
A separate diagnosis of obsessive-compulsive and related disorder due to another 
medical 
condition is not 
given if the disturbance occurs exclusively during the course of a 
delirium. However, a diagnosis of obsessive-compulsive and related disorder due to 


293 



another medical 
condition may be given in addition to a diagnosis of major neurocognitive 
disorder (dementia) if the etiology of the obsessive-compulsive symptoms is judged to be a 
physiological 
consequence of the pathological 
process causing the dementia and if obsessive-
compulsive symptoms are a prominent part of the clinical presentation. 


Mixed 
presentation 
of 
symptoms 
(e.g., 
mood 
and 
obsessive-compulsive 
and 
related 
symptoms) 
judged 
to 
be 
due 
to 
another medical 
condition. 


If the presentation includes a mix of different 
types of symptoms, the specific mental 
disorder 
due to another medical 
condition depends on which symptoms predominate in the clinical 
picture. 


Substance/medication-induced 
obsessive-compulsive 
and 
related 
disorders. 


If there is evidence of 
recent 
or prolonged substance use (including medications with psychoactive effects), withdrawal 
from 
a substance, or exposure to a toxin, a substance/medication-induced obsessive-compulsive 
and related disorder should be considered. When a substance/medication-induced obsessive-
compulsive and related disorder is being diagnosed in relation to drugs of abuse, it 
may be useful 
to obtain a urine or blood drug screen or other appropriate laboratory evaluation. Symptoms that 
occur during or shortly after (i.e., within 4 weeks of) substance intoxication or withdrawal 
or 
after medication use may be especially indicative of a substance/medication-induced obsessive-
compulsive and related disorder, depending on the type, duration, or amount 
of the substance 
used. 
Obsessive-compulsive 
and 
related 
disorders 
(primary). 
Obsessive-compulsive and related disorder 


due to another medical 
condition should be distinguished from 
a primary obsessive-compulsive 
and related disorder. In primary mental 
disorders, no specific and direct 
causative physiological 
mechanisms associated with a medical 
condition can be demonstrated. Acute-onset 
symptoms, 
late age at 
onset, or atypical 
symptoms suggest 
the need for a thorough assessment 
to rule out 
the 
diagnosis of obsessive-compulsive and related disorder due to another medical condition. 


Illness 
anxiety 
disorder. 
Illness anxiety disorder is characterized by a preoccupation with having 
or acquiring a serious illness. In the case of illness anxiety disorder, individuals may or may not 
have diagnosed medical conditions. 


Associated 
feature 
of 
another mental 
disorder. 
Obsessive-compulsive and related symptoms may be 
an associated feature of another mental disorder (e.g., schizophrenia, anorexia nervosa). 


Other specified 
obsessive-compulsive 
and 
related 
disorder or unspecified 
obsessive-
compulsive 
and 
related 
disorder. 


These diagnoses are given if it 
is unclear whether the obsessive-compulsive and related 
symptoms are primary, substance-induced, or due to another medical condition. 


Other Specified 
Obsessive-Compulsive and 
Related 
Disorder 


F42.8 


This category applies to 
presentations in 
which 
symptoms characteristic of 
an 
obsessive-compulsive 
and 
related 
disorder that 
cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 



predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
obsessive-compulsive 
and 
related 
disorders diagnostic class. 
The 
other specified 
obsessive-compulsive 
and 
related 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does 
not 
meet 
the 
criteria 
for any specific obsessive-compulsive 
and 
related 
disorder. 
This 
is done 
by recording 
 other specified 
obsessive-compulsive 
and 
related 
disorder  
followed 
by the 
specific reason 
(e.g., 
 obsessional jealousy ). 


294 


Examples of 
presentations that 
can 
be 
specified 
using 
the 
 other specified  
designation 
include 
the 
following: 


1. 
Body 
dysmorphic like 
disorder with 
actual 
flaws: 
This is similar to 
body 
dysmorphic disorder except 
that 
the 
defects or flaws in 
physical appearance 
are 
clearly observable 
by others (i.e., 
they are 
more 
noticeable 
than 
 slight ). 
In 
such 
cases, 
the 
preoccupation 
with 
these 
flaws is clearly excessive 
and 
causes 
significant 
impairment 
or distress. 
2. 
Body 
dysmorphic like 
disorder without repetitive 
behaviors: 
Presentations 
that 
meet 
body dysmorphic disorder except 
that 
the 
individual has never 
performed 
repetitive 
behaviors or mental acts in 
response 
to 
the 
appearance 
concerns. 
3. 
Other body-focused 
repetitive 
behavior disorder: 
Presentations involving 
recurrent 
body-focused 
repetitive 
behaviors other than 
hair pulling 
and 
skin 
picking 
(e.g., 
nail biting, 
lip 
biting, 
cheek chewing) that 
are 
accompanied 
by 
repeated 
attempts to 
decrease 
or stop 
the 
behaviors and 
that 
cause 
clinically 
significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas 
of 
functioning. 
4. 
Obsessional 
jealousy: 
This is characterized 
by nondelusional preoccupation 
with 
a 
partner s perceived 
infidelity. 
The 
preoccupations may lead 
to 
repetitive 
behaviors or mental acts in 
response 
to 
the 
infidelity concerns; 
they cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other 
important 
areas of 
functioning; 
and 
they are 
not 
better explained 
by another 
mental disorder such 
as delusional disorder, 
jealous type, 
or paranoid 
personality 
disorder. 
5. 
Olfactory 
reference 
disorder (olfactory 
reference 
syndrome): 
This is 
characterized 
by the 
individual s persistent 
preoccupation 
with 
the 
belief 
that 
he 
or she 
emits a 
foul or offensive 
body odor that 
is unnoticeable 
or only slightly 
noticeable 
to 
others; 
in 
response 
to 
this preoccupation, 
these 
individuals often 
engage 
in 
repetitive 
and 
excessive 
behaviors such 
as repeatedly checking 
for 
body odor, 
excessive 
showering, 
or seeking 
reassurance, 
as well as excessive 
attempts to 
camouflage 
the 
perceived 
odor. 
These 
symptoms cause 
clinically 
significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas 
of 
functioning. 
In 
traditional Japanese 
psychiatry, 
this disorder is known 
as 
jikoshu-kyofu, 
a 
variant 
of 
taijin 
kyofusho 
(see 
 Culture 
and 
Psychiatric 
Diagnosis  in 
Section 
III). 

6. 
Shubo-kyofu: 
A 
variant 
of 
taijin 
kyofusho 
(see 
 Culture 
and 
Psychiatric 
Diagnosis  in 
Section 
III) that 
is similar to 
body dysmorphic disorder and 
is 
characterized 
by excessive 
fear of 
having 
a 
bodily deformity. 
7. 
Koro: 
Related 
to 
dhat 
syndrome 
(see 
 Culture 
and 
Psychiatric Diagnosis  in 
Section 
III), 
an 
episode 
of 
sudden 
and 
intense 
anxiety that 
the 
penis in 
males (or 
the 
vulva 
and 
nipples in 
females) will recede 
into 
the 
body, 
possibly leading 
to 
death. 
Unspecified 
Obsessive-Compulsive and 
Related 
Disorder 


F42.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
an 
obsessive-compulsive 
and 
related 
disorder that 
cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
obsessive-compulsive 
and 
related 
disorders diagnostic class. 
The 
unspecified 
obsessive-compulsive 
and 
related 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific obsessive-compulsive 
and 
related 
disorder and 
includes presentations in 
which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room settings). 



295 



Trauma- and Stressor-Related Disorders 


Trauma- and stressor-related disorders include disorders 
in which 


exposure to a traumatic or stressful 
event 
is listed explicitly as a diagnostic criterion. These 
include reactive attachment 
disorder, disinhibited social 
engagement 
disorder, posttraumatic 
stress disorder (PTSD), acute stress disorder, adjustment 
disorders, and prolonged grief disorder. 
Placement 
of this chapter reflects the close relationship between these diagnoses and disorders in 
the surrounding chapters on anxiety disorders, obsessive-compulsive and related disorders, and 
dissociative disorders. 


Psychological 
distress following exposure to a traumatic or stressful 
event 
is quite variable. 
In some cases, symptoms can be well 
understood within an anxiety- or fear-based context. It 
is 
clear, however, that 
many individuals who have been exposed to a traumatic or stressful 
event 
exhibit 
a phenotype in which, rather than anxiety- or fear-based symptoms, the most 
prominent 
clinical 
characteristics are anhedonic and dysphoric symptoms, externalizing angry and 
aggressive symptoms, or dissociative symptoms. Because of these variable expressions of 
clinical 
distress following exposure to catastrophic or aversive events, the aforementioned 
disorders are grouped under a separate category: 
trauma- and stressor-related disorders. 
Furthermore, it 
is not 
uncommon for the clinical 
picture to include some combination of the 
above symptoms (with or without 
anxiety- or fear-based symptoms). Such a heterogeneous 
picture has long been recognized in adjustment 
disorders, as well. Social 
neglect that 
is, the 
absence of adequate caregiving during childhood is a diagnostic requirement 
of both reactive 
attachment 
disorder and disinhibited social 
engagement 
disorder. Although the two disorders 
share a common etiology, the former is expressed as an internalizing disorder with depressive 
symptoms and withdrawn behavior, while the latter is marked by disinhibition and externalizing 
behavior. Finally, it 
has long been recognized that 
whereas grief, despair, and general 
dysphoria 
can be a part 
of the normal 
grieving process after the death of a loved one, the expression of such 
emotions is sometimes abnormally excessive in duration and/or intensity. The diagnosis of 
prolonged grief disorder has been introduced in this chapter to meet this clinical concern. 


Reactive Attachment Disorder 


Diagnostic Criteria 
F94.1 


A. 
A 
consistent 
pattern 
of 
inhibited, 
emotionally withdrawn 
behavior toward 
adult 
caregivers, 
manifested 
by both 
of 
the 
following: 
1. 
The 
child 
rarely or minimally seeks comfort 
when 
distressed. 
2. 
The 
child 
rarely or minimally responds to 
comfort 
when 
distressed. 

B. 
A 
persistent 
social and 
emotional disturbance 
characterized 
by at 
least 
two 
of 
the 
following: 
1. 
Minimal social and 
emotional responsiveness to 
others. 
2. 
Limited 
positive 
affect. 
296 


3. 
Episodes of 
unexplained 
irritability, 
sadness, 
or fearfulness that 
are 
evident 
even 
during 
nonthreatening 
interactions with 
adult 
caregivers. 
C. 
The 
child 
has experienced 
a 
pattern 
of 
extremes of 
insufficient 
care 
as 
evidenced 
by at 
least 
one 
of 
the 
following: 
1. 
Social neglect 
or deprivation 
in 
the 
form of 
persistent 
lack of 
having 
basic 
emotional needs for comfort, 
stimulation, 
and 
affection 
met 
by caregiving 
adults. 
2. 
Repeated 
changes of 
primary caregivers that 
limit 
opportunities to 
form stable 
attachments (e.g., 
frequent 
changes in 
foster care). 
3. 
Rearing 
in 
unusual settings that 
severely limit 
opportunities to 
form selective 
attachments (e.g., 
institutions with 
high 
child-to-caregiver ratios). 
D. 
The 
care 
in 
Criterion 
C is presumed 
to 
be 
responsible 
for the 
disturbed 
behavior 
in 
Criterion 
A 
(e.g., 
the 
disturbances in 
Criterion 
A 
began 
following 
the 
lack of 
adequate 
care 
in 
Criterion 
C). 
E. 
The 
criteria 
are 
not 
met 
for autism spectrum disorder. 
F. 
The 
disturbance 
is evident 
before 
age 
5 
years. 
G. 
The 
child 
has a 
developmental age 
of 
at 
least 
9 
months. 
Specify 
if: 
Persistent: 
The 
disorder has been 
present 
for more 
than 
12 
months. 
Specify 
current 
severity: 
Reactive 
attachment 
disorder is specified 
as severe 
when 
a 
child 
exhibits all 
symptoms of 
the 
disorder, 
with 
each 
symptom manifesting 
at 
relatively high 
levels. 


Diagnostic Features 


Reactive attachment 
disorder is characterized by a pattern of markedly disturbed and 
developmentally inappropriate attachment 
behaviors, in which a child rarely or minimally turns 
preferentially to an attachment 
figure for comfort, support, protection, and nurturance. The 
essential 
feature is absent 
or grossly underdeveloped attachment 
between the child and putative 
caregiving adults. Children with reactive attachment 
disorder are believed to have the capacity to 
form selective attachments. However, because of limited opportunities during early development, 
they fail 
to show the behavioral 
manifestations of selective attachments. That 
is, when distressed, 
they show no consistent 
effort 
to obtain comfort, support, nurturance, or protection from 
caregivers. Furthermore, when distressed, children with this disorder do not 
respond more than 



minimally to comforting efforts of caregivers. Thus, the disorder is associated with the absence 
of expected comfort 
seeking and response to comforting behaviors. As such, children with 
reactive attachment 
disorder show diminished or absent 
expression of positive emotions during 
routine interactions with caregivers. In addition, their emotion regulation capacity is 
compromised, and they display episodes of negative emotions of fear, sadness, or irritability that 
are not 
readily explained. A diagnosis of reactive attachment 
disorder should not 
be made in 
children who are developmentally unable to form 
selective attachments. For this reason, the child 
must 
have a developmental 
age of at 
least 
9 months. Diagnostic assessment 
is enhanced by 
multiple sources of input, supporting that the symptoms are apparent across contexts. 


Associated Features 


Because of the shared etiological 
association with social 
neglect, reactive attachment 
disorder 
often co-occurs with developmental 
delays, especially in delays in cognition and language. Other 
associated features include stereotypies and other signs of severe neglect 
(e.g., malnutrition or 
signs of poor care). 


297 


Prevalence 


The prevalence of reactive attachment 
disorder is unknown, but 
the disorder is seen relatively 
rarely in clinical 
settings. The disorder has been found in young children exposed to severe 
neglect 
before being placed in foster care or raised in institutions. The disorder is uncommon, 
usually occurring in less than 10% of neglected children, even in cases of severe neglect. 


Development and Course 


Conditions of social 
neglect 
are often present 
in the first 
months of life in children diagnosed 
with reactive attachment 
disorder, even before the disorder is diagnosed. The clinical 
features of 
the disorder manifest 
in a similar fashion between the ages of 9 months and 5 years. That 
is, 
signs of absent-to-minimal 
attachment 
behaviors and associated 
emotionally aberrant 
behaviors 
are evident 
in children throughout 
this age range, although differing cognitive and motor abilities 
may affect 
how these behaviors are expressed. Remediation and symptomatic recovery may 
occur through normative caregiving environments; 
however, in the absence of enhanced 
caregiving, the signs of the disorder may persist, at 
least 
for several 
years. Persistent 
signs of 
reactive attachment 
disorder in early adolescence may be associated with problems in social 
functioning. Less is known about 
the clinical 
presentation of reactive attachment 
disorder in 
older children, and the diagnosis should be made with caution in children older than 5 years. 


Risk and Prognostic Factors 


Environmental. 
Serious social 
neglect 
is a diagnostic requirement 
for reactive attachment 
disorder 
and is also the only known risk factor for the disorder. However, the majority of severely 
neglected children do not 
develop the disorder. Prognosis for children with the disorder appears 
to depend on the quality of the caregiving environment following serious neglect. 



Culture-Related Diagnostic Issues 


There is limited information on reactive attachment 
behavior in young children from 
diverse 
cultural 
backgrounds around the world. Cultural 
expectations of attachment 
behaviors and 
caregiving practices may influence development of and concern about these patterns of behaviors 
and their presentations in different 
settings. Caution should be exercised in making the diagnosis 
of reactive attachment 
disorder in cultural 
contexts in which attachment 
has not 
been studied. 
Symptoms of reactive attachment 
disorder may be more common in situations where attachment 
figures have experienced extensive trauma, such as war-zone settings; attachment styles may also 
vary among migrant 
and refugee children during the resettlement 
period. Variations in nurturing 
care practices may influence risk of reactive attachment disorder. 


Functional 
Consequences of Reactive Attachment Disorder 


Reactive attachment 
disorder significantly impairs young children s abilities to relate 
interpersonally to adults or peers and is associated with functional 
impairment 
across many 
domains of early childhood. 


Differential 
Diagnosis 


Autism spectrum disorder. 
Aberrant 
social 
behaviors manifest 
in young children with reactive 
attachment 
disorder, but 
they also are key features of autism 
spectrum 
disorder. Specifically, 
young children with either condition can manifest 
dampened expression of positive emotions, 
cognitive and language delays, and impairments in social 
reciprocity. As a result, reactive 
attachment disorder must be differentiated from autism spectrum disorder. These 


298 


two disorders can be distinguished based on differential 
histories of neglect 
and on the presence 
of restricted interests or ritualized behaviors, specific deficit 
in social 
communication, and 
selective attachment 
behaviors. Children with reactive attachment 
disorder have experienced a 
history of severe social 
neglect, although it 
is not 
always possible to obtain detailed histories 
about 
the precise nature of their experiences, especially in initial 
evaluations. Children with 
autism 
spectrum 
disorder will 
only rarely have a history of social 
neglect. The restricted interests 
and repetitive behaviors characteristic of autism 
spectrum 
disorder are not 
a feature of reactive 
attachment 
disorder. These clinical 
features manifest 
as excessive adherence to rituals and 
routines; 
restricted, fixated interests; 
and unusual 
sensory reactions. However, it 
is important 
to 
note that 
children with either condition can exhibit 
stereotypic behaviors such as rocking or 
flapping. Children with either disorder also may exhibit 
a range of intellectual 
functioning, but 
only children with autism 
spectrum 
disorder exhibit 
selective impairments in social 
communicative behaviors, such as intentional 
communication (i.e., impairment 
in 
communication that 
is deliberate, goal-directed, and aimed at 
influencing the behavior of the 
recipient). Children with reactive attachment 
disorder show social 
communicative functioning 
comparable to their overall 
level 
of intellectual 
functioning. Finally, children with autism 
spectrum 
disorder regularly show attachment 
behavior typical 
for their developmental 
level. In 
contrast, children with reactive attachment 
disorder do so only rarely or inconsistently, if at 
all. 
Structured observations can help discriminate between the two disorders. 



Intellectual 
developmental 
disorder (intellectual 
disability). 
Developmental 
delays often accompany 
reactive attachment 
disorder, but 
they should not 
be confused with the disorder. Children with 
intellectual 
developmental 
disorder should exhibit 
social 
and emotional 
skills comparable to their 
cognitive skills and do not 
demonstrate the profound reduction in positive affect 
and emotion 
regulation difficulties evident 
in children with reactive attachment 
disorder. In addition, 
developmentally delayed children who have reached a cognitive age of 7 9 months should 
demonstrate selective attachments regardless of their chronological 
age. In contrast, children 


with reactive attachment 
disorder show lack of preferred attachment 
despite having attained a 
developmental age of at least 9 months. 
Depressive 
disorders. 
Depression in young children is also associated with reductions in positive 


affect. There is limited evidence, however, to suggest 
that 
children with depressive disorders 
have impairments in attachment. That 
is, young children who have been diagnosed with 
depressive disorders still should seek and respond to comforting efforts by caregivers. 


Comorbidity 


Conditions associated with neglect, including cognitive delays, language delays, and 
stereotypies, often co-occur with reactive attachment 
disorder. Medical 
conditions, such as 
severe malnutrition, may accompany signs of the disorder. Internalizing symptoms also may co-
occur with reactive attachment 
disorder. A relationship between reactive attachment 
disorder and 
externalizing behavior problems or attention-deficit/hyperactivity disorder (ADHD) has been 
suggested but not clearly established. 


Disinhibited 
Social 
Engagement Disorder 


Diagnostic Criteria 
F94.2 


A. 
A 
pattern 
of 
behavior in 
which 
a 
child 
actively approaches and 
interacts with 
unfamiliar adults and 
exhibits at 
least 
two 
of 
the 
following: 
1. 
Reduced 
or absent 
reticence 
in 
approaching 
and 
interacting 
with 
unfamiliar 
adults. 
2. 
Overly familiar verbal or physical behavior (that 
is not 
consistent 
with 
culturally sanctioned 
and 
with 
age-appropriate 
social boundaries). 
299 


3. 
Diminished 
or absent 
checking 
back with 
adult 
caregiver after venturing 
away, 
even 
in 
unfamiliar settings. 
4. 
Willingness to 
go 
off 
with 
an 
unfamiliar adult 
with 
minimal or no 
hesitation. 
B. 
The 
behaviors in 
Criterion 
A 
are 
not 
limited 
to 
impulsivity (as in 
attentiondeficit/
hyperactivity disorder) but 
include 
socially disinhibited 
behavior. 
C. 
The 
child 
has experienced 
a 
pattern 
of 
extremes of 
insufficient 
care 
as 

evidenced 
by at 
least 
one 
of 
the 
following: 


1. 
Social neglect 
or deprivation 
in 
the 
form of 
persistent 
lack of 
having 
basic 
emotional needs for comfort, 
stimulation, 
and 
affection 
met 
by caregiving 
adults. 
2. 
Repeated 
changes of 
primary caregivers that 
limit 
opportunities to 
form stable 
attachments (e.g., 
frequent 
changes in 
foster care). 
3. 
Rearing 
in 
unusual settings that 
severely limit 
opportunities to 
form selective 
attachments (e.g., 
institutions with 
high 
child-to-caregiver ratios). 
D. 
The 
care 
in 
Criterion 
C is presumed 
to 
be 
responsible 
for the 
disturbed 
behavior 
in 
Criterion 
A 
(e.g., 
the 
disturbances in 
Criterion 
A 
began 
following 
the 
pathogenic care 
in 
Criterion 
C). 
E. 
The 
child 
has a 
developmental age 
of 
at 
least 
9 
months. 
Specify 
if: 
Persistent: 
The 
disorder has been 
present 
for more 
than 
12 
months. 
Specify 
current 
severity: 
Disinhibited 
social engagement 
disorder is specified 
as severe 
when 
the 
child 
exhibits all symptoms of 
the 
disorder, 
with 
each 
symptom manifesting 
at 
relatively high 
levels. 


Diagnostic Features 


The essential 
feature of disinhibited social 
engagement 
disorder is a pattern of behavior that 
involves culturally inappropriate, overly familiar behavior with relative strangers (Criterion A). 
This overly familiar behavior violates the social 
boundaries of the culture. A diagnosis of 
disinhibited social 
engagement 
disorder should not 
be made before children are developmentally 
able to form 
selective attachments. For this reason, the child must 
have a developmental 
age of at 
least 9 months. 


Associated Features 


Because of the shared etiological 
association with social 
neglect, disinhibited social 
engagement 
disorder may co-occur with developmental 
delays, especially cognitive and language delays, 
stereotypies, and other signs of severe neglect, such as malnutrition or poor care. However, signs 
of the disorder often persist 
even after these other signs of neglect 
are no longer present. 
Therefore, it 
is not 
uncommon for children with the disorder to present 
with no current 
signs of 
neglect. Moreover, the condition can present 
in children who show no signs of disordered 
attachment. Thus, disinhibited social 
engagement 
disorder may be seen in children with a history 
of neglect 
who lack attachments or whose attachments to their caregivers range from 
disturbed to 
secure. 


Prevalence 


The prevalence of disinhibited social 
engagement 
disorder is unknown. Nevertheless, the 
disorder appears to be rare, occurring in a minority of children, even those who have experienced 



severe early deprivation. In low-income community populations in the United Kingdom, the 
prevalence is up to 2%. 


300 


Development and Course 


Conditions of social 
neglect 
are often present 
in the first 
months of life in children diagnosed 
with disinhibited social 
engagement 
disorder, even before the disorder is diagnosed. As noted by 
research among children with a history of institutional 
care, if neglect 
occurs early and signs of 
the disorder appear, clinical 
features of the disorder are moderately stable over time, particularly 
if conditions of neglect persist. 


Signs of disinhibited social 
engagement 
disorder have been described from 
the second year 
of life through adolescence among children raised in institutional 
settings, and even into young 
adulthood. There are some differences in manifestations of the disorder from 
early childhood to 
older ages. At 
the youngest 
ages, across many cultures, children typically show reticence when 
interacting with strangers, which is nonpathological, even if they are raised in institutions and 
foster care. Young children with the disorder, however, fail 
to show reticence to approach and 
are found to engage with, and even accompany, unfamiliar adults without 
hesitation, as shown 
by research among children with a history of institutionalized care. In preschool 
children raised 
in institutional 
settings in the United Kingdom 
or the United States, verbal 
and social 
intrusiveness appeared most 
prominent, often accompanied by attention-seeking behavior; 
preschool 
children raised in institutional 
settings across several 
countries have displayed a 
pattern of engaging in physical 
contact 
with strangers. Verbal 
and physical 
overfamiliarity 
continued through middle childhood, sometimes accompanied by inauthentic expressions of 
emotion. In adolescence, indiscriminate behavior may extend to peers. Relative to healthy 
adolescents, adolescents with the disorder have more  superficial  peer relationships and more 
peer conflicts. Adult 
manifestations of the disorder appear to be similar but 
may include 
excessive self-disclosure and reduced stranger awareness. 


Risk and Prognostic Factors 


Temperamental. 
There is some evidence from 
research with international 
adoptees in the United 
States that 
both blunted reward sensitivity and decreased inhibitory control 
are associated with 
indiscriminate social behavior. 


Environmental. 
Serious social 
neglect 
is a diagnostic requirement 
for disinhibited social 
engagement 
disorder. The rationale for this requirement 
includes research finding a strong 
association between neglect 
and features of the disorder. Other factors also have been implicated, 
such as multiple placement 
disruptions, borderline personality disorder in the mother, and 
aberrant 
caregiving behaviors and low quality of care. All 
of these contribute to the insufficient 
care criterion. Still, the majority of severely neglected children do not 
develop the disorder. The 
disorder has not 
been identified in children who experience social 
neglect 
only after age 2 years. 
Prognosis is only modestly associated with quality of the caregiving environment 
following 
serious neglect. In many cases, the disorder persists, even in children whose caregiving 
environment becomes markedly improved. 



Genetic 
and 
physiological. 
Various neurobiological factors have been associated with symptoms of 
the disorder, but 
findings concerning the nature of such factors and their specific tie to the 
disorder remain preliminary. 


Course 
modifiers. 
Caregiving quality seems to moderate the course of disinhibited social 
engagement 
disorder, at 
least 
in young children. Nevertheless, even after placement 
in normative 
caregiving environments, some children show persistent 
signs of the disorder, through 
adolescence and into adulthood. 


Culture-Related Diagnostic Issues 


There is limited cross-cultural 
information on disinhibited social 
engagement 
disorder. Cultural 
expectations of children s social behaviors may affect their level of disinhibition 


301 


toward strangers. The absence of reticence that is characteristic of disinhibited social engagement 
disorder should exceed culturally accepted norms. 


Functional 
Consequences of Disinhibited Social 
Engagement Disorder 


Disinhibited social 
engagement 
disorder significantly impairs young children s abilities to relate 
interpersonally to adults and peers. Both general 
social 
functioning and social 
competence may 
be impaired, along with increased risk for peer conflicts and victimization. 


Differential 
Diagnosis 


Attention-deficit/hyperactivity 
disorder. 
Children with disinhibited social 
engagement 
disorder can 
be distinguished from those with ADHD accompanied by social impulsivity, as the former do not 
show difficulties with attention or hyperactivity. 


Comorbidity 


Conditions associated with neglect, including cognitive delays, language delays, and 
stereotypies, may co-occur with disinhibited social 
engagement 
disorder. Autism 
spectrum 
disorder may also co-occur. In younger children and in middle childhood, disinhibited social 
engagement 
disorder often co-occurs with ADHD and externalizing disorders; 
this co-occurrence 
has been proposed to relate to common impairments in cognitive inhibitory control. 


Posttraumatic Stress Disorder 


Diagnostic Criteria 
F43.10 


PosttraumaticStressDisorder inIndividualsOlder Than6Years
Note: 
The 
following 
criteria 
apply to 
adults, 
adolescents, 
and 
children 
older than 
6 



years. 
For children 
6 
years and 
younger, 
see 
corresponding 
criteria 
below. 


A. 
Exposure 
to 
actual or threatened 
death, 
serious injury, 
or sexual violence 
in 
one 
(or more) of 
the 
following 
ways: 
1. 
Directly experiencing 
the 
traumatic event(s). 
2. 
Witnessing, 
in 
person, 
the 
event(s) as it 
occurred 
to 
others. 
3. 
Learning 
that 
the 
traumatic event(s) occurred 
to 
a 
close 
family member or 
close 
friend. 
In 
cases of 
actual or threatened 
death 
of 
a 
family member or 
friend, 
the 
event(s) must 
have 
been 
violent 
or accidental. 
4. 
Experiencing 
repeated 
or extreme 
exposure 
to 
aversive 
details of 
the 
traumatic event(s) (e.g., 
first 
responders collecting 
human 
remains; 
police 
officers repeatedly exposed 
to 
details of 
child 
abuse). 
Note: 
Criterion 
A4 
does not 
apply to 
exposure 
through 
electronic media, 
television, 
movies, 
or pictures, 
unless this exposure 
is work related. 


B. 
Presence 
of 
one 
(or more) of 
the 
following 
intrusion 
symptoms associated 
with 
the 
traumatic event(s), 
beginning 
after the 
traumatic event(s) occurred: 
1. 
Recurrent, 
involuntary, 
and 
intrusive 
distressing 
memories of 
the 
traumatic 
event(s). 
Note: 
In 
children 
older than 
6 
years, 
repetitive 
play may occur in 
which 
themes or aspects of 
the 
traumatic event(s) are 
expressed. 


302 


2. 
Recurrent 
distressing 
dreams in 
which 
the 
content 
and/or affect 
of 
the 
dream 
are 
related 
to 
the 
traumatic event(s). 
Note: 
In 
children, 
there 
may be 
frightening 
dreams without 
recognizable 
content. 


3. 
Dissociative 
reactions (e.g., 
flashbacks) in 
which 
the 
individual feels or acts 
as if 
the 
traumatic event(s) were 
recurring. 
(Such 
reactions may occur on 
a 
continuum, 
with 
the 
most 
extreme 
expression 
being 
a 
complete 
loss of 
awareness of 
present 
surroundings.) 
Note: 
In 
children, 
trauma-specific reenactment 
may occur in 
play. 


4. 
Intense 
or prolonged 
psychological distress at 
exposure 
to 
internal or external 
cues that 
symbolize 
or resemble 
an 
aspect 
of 
the 
traumatic event(s). 
5. 
Marked 
physiological reactions to 
internal or external cues that 
symbolize 
or 
resemble 
an 
aspect 
of 
the 
traumatic event(s). 
C. 
Persistent 
avoidance 
of 
stimuli associated 
with 
the 
traumatic event(s), 
beginning 
after the 
traumatic event(s) occurred, 
as evidenced 
by one 
or both 
of 
the 
following: 
1. 
Avoidance 
of 
or efforts to 
avoid 
distressing 
memories, 
thoughts, 
or feelings 
about 
or closely associated 
with 
the 
traumatic event(s). 
2. 
Avoidance 
of 
or efforts to 
avoid 
external reminders (people, 
places, 

conversations, 
activities, 
objects, 
situations) that 
arouse 
distressing 
memories, 
thoughts, 
or feelings about 
or closely associated 
with 
the 
traumatic 
event(s). 


D. 
Negative 
alterations in 
cognitions and 
mood 
associated 
with 
the 
traumatic 
event(s), 
beginning 
or worsening 
after the 
traumatic event(s) occurred, 
as 
evidenced 
by two 
(or more) of 
the 
following: 
1. 
Inability to 
remember an 
important 
aspect 
of 
the 
traumatic event(s) (typically 
due 
to 
dissociative 
amnesia 
and 
not 
to 
other factors such 
as head 
injury, 
alcohol, 
or drugs). 
2. 
Persistent 
and 
exaggerated 
negative 
beliefs or expectations about 
oneself, 
others, 
or the 
world 
(e.g., 
 I 
am bad,   No 
one 
can 
be 
trusted,   The 
world 
is 
completely dangerous,   My whole 
nervous system is permanently ruined ). 
3. 
Persistent, 
distorted 
cognitions about 
the 
cause 
or consequences of 
the 
traumatic event(s) that 
lead 
the 
individual to 
blame 
himself/herself 
or others. 
4. 
Persistent 
negative 
emotional state 
(e.g., 
fear, 
horror, 
anger, 
guilt, 
or shame). 
5. 
Markedly diminished 
interest 
or participation 
in 
significant 
activities. 
6. 
Feelings of 
detachment 
or estrangement 
from others. 
7. 
Persistent 
inability to 
experience 
positive 
emotions (e.g., 
inability to 
experience 
happiness, 
satisfaction, 
or loving 
feelings). 
E. 
Marked 
alterations in 
arousal and 
reactivity associated 
with 
the 
traumatic 
event(s), 
beginning 
or worsening 
after the 
traumatic event(s) occurred, 
as 
evidenced 
by two 
(or more) of 
the 
following: 
1. 
Irritable 
behavior and 
angry outbursts (with 
little 
or no 
provocation) typically 
expressed 
as verbal or physical aggression 
toward 
people 
or objects. 
2. 
Reckless or self-destructive 
behavior. 
3. 
Hypervigilance. 
4. 
Exaggerated 
startle 
response. 
5. 
Problems with 
concentration. 
6. 
Sleep 
disturbance 
(e.g., 
difficulty falling 
or staying 
asleep 
or restless sleep). 
F. 
Duration 
of 
the 
disturbance 
(Criteria 
B, 
C, 
D, 
and 
E) is more 
than 
1 
month. 
G. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
303 


H. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
medication, 
alcohol) or another medical condition. 
Specify 
whether: 
With 
dissociative 
symptoms: 
The 
individual s symptoms meet 
the 
criteria 
for 
posttraumatic stress disorder, 
and 
in 
addition, 
in 
response 
to 
the 
stressor, 
the 
individual experiences persistent 
or recurrent 
symptoms of 
either of 
the 



following: 


1. 
Depersonalization: 
Persistent 
or recurrent 
experiences of 
feeling 
detached 
from, 
and 
as if 
one 
were 
an 
outside 
observer of, 
one s mental processes or 
body (e.g., 
feeling 
as though 
one 
were 
in 
a 
dream; 
feeling 
a 
sense 
of 
unreality 
of 
self 
or body or of 
time 
moving 
slowly). 
2. 
Derealization: 
Persistent 
or recurrent 
experiences of 
unreality of 
surroundings 
(e.g., 
the 
world 
around 
the 
individual is experienced 
as unreal, 
dreamlike, 
distant, 
or distorted). 
Note: 
To 
use 
this subtype, 
the 
dissociative 
symptoms must 
not 
be 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
blackouts, 
behavior during 
alcohol 
intoxication) or another medical condition 
(e.g., 
complex partial seizures). 


Specify 
if: 
With 
delayed 
expression: 
If 
the 
full diagnostic criteria 
are 
not 
met 
until at 
least 
6 
months after the 
event 
(although 
the 
onset 
and 
expression 
of 
some 
symptoms 
may be 
immediate). 


PosttraumaticStressDisorder inChildren6YearsandYounger
A. 
In 
children 
6 
years and 
younger, 
exposure 
to 
actual or threatened 
death, 
serious 
injury, 
or sexual violence 
in 
one 
(or more) of 
the 
following 
ways: 
1. 
Directly experiencing 
the 
traumatic event(s). 
2. 
Witnessing, 
in 
person, 
the 
event(s) as it 
occurred 
to 
others, 
especially primary 
caregivers. 
3. 
Learning 
that 
the 
traumatic event(s) occurred 
to 
a 
parent 
or caregiving 
figure. 
B. 
Presence 
of 
one 
(or more) of 
the 
following 
intrusion 
symptoms associated 
with 
the 
traumatic event(s), 
beginning 
after the 
traumatic event(s) occurred: 
1. 
Recurrent, 
involuntary, 
and 
intrusive 
distressing 
memories of 
the 
traumatic 
event(s). 
Note: 
Spontaneous and 
intrusive 
memories may not 
necessarily appear 
distressing 
and 
may be 
expressed 
as play reenactment. 


2. 
Recurrent 
distressing 
dreams in 
which 
the 
content 
and/or affect 
of 
the 
dream 
are 
related 
to 
the 
traumatic event(s). 
Note: 
It 
may not 
be 
possible 
to 
ascertain 
that 
the 
frightening 
content 
is 
related 
to 
the 
traumatic event. 


3. 
Dissociative 
reactions (e.g., 
flashbacks) in 
which 
the 
child 
feels or acts as if 
the 
traumatic event(s) were 
recurring. 
(Such 
reactions may occur on 
a 
continuum, 
with 
the 
most 
extreme 
expression 
being 
a 
complete 
loss of 
awareness of 
present 
surroundings.) Such 
trauma-specific reenactment 
may 
occur in 
play. 
4. 
Intense 
or prolonged 
psychological distress at 
exposure 
to 
internal or external 
cues that 
symbolize 
or resemble 
an 
aspect 
of 
the 
traumatic event(s). 

5. 
Marked 
physiological reactions to 
reminders of 
the 
traumatic event(s). 
C. 
One 
(or more) of 
the 
following 
symptoms, 
representing 
either persistent 
avoidance 
of 
stimuli associated 
with 
the 
traumatic event(s) or negative 
alterations in 
cognitions and 
304 


mood 
associated 
with 
the 
traumatic event(s), 
must 
be 
present, 
beginning 
after 
the 
event(s) or worsening 
after the 
event(s): 


Persistent Avoidance 
of Stimuli 


1. 
Avoidance 
of 
or efforts to 
avoid 
activities, 
places, 
or physical reminders that 
arouse 
recollections of 
the 
traumatic event(s). 
2. 
Avoidance 
of 
or efforts to 
avoid 
people, 
conversations, 
or interpersonal 
situations that 
arouse 
recollections of 
the 
traumatic event(s). 
Negative 
Alterations 
in 
Cognitions 


3. 
Substantially increased 
frequency of 
negative 
emotional states (e.g., 
fear, 
guilt, 
sadness, 
shame, 
confusion). 
4. 
Markedly diminished 
interest 
or participation 
in 
significant 
activities, 
including 
constriction 
of 
play. 
5. 
Socially withdrawn 
behavior. 
6. 
Persistent 
reduction 
in 
expression 
of 
positive 
emotions. 
D. 
Alterations in 
arousal and 
reactivity associated 
with 
the 
traumatic event(s), 
beginning 
or worsening 
after the 
traumatic event(s) occurred, 
as evidenced 
by 
two 
(or more) of 
the 
following: 
1. 
Irritable 
behavior and 
angry outbursts (with 
little 
or no 
provocation) typically 
expressed 
as verbal or physical aggression 
toward 
people 
or objects 
(including 
extreme 
temper tantrums). 
2. 
Hypervigilance. 
3. 
Exaggerated 
startle 
response. 
4. 
Problems with 
concentration. 
5. 
Sleep 
disturbance 
(e.g., 
difficulty falling 
or staying 
asleep 
or restless sleep). 
E. 
The 
duration 
of 
the 
disturbance 
is more 
than 
1 
month. 
F. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
relationships with 
parents, 
siblings, 
peers, 
or other caregivers or with 
school 
behavior. 
G. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
medication 
or alcohol) or another medical condition. 
Specify 
whether: 
With 
dissociative 
symptoms: 
The 
individual s symptoms meet 
the 
criteria 
for 
posttraumatic stress disorder, 
and 
the 
individual experiences persistent 
or 
recurrent 
symptoms of 
either of 
the 
following: 



1. 
Depersonalization: 
Persistent 
or recurrent 
experiences of 
feeling 
detached 
from, 
and 
as if 
one 
were 
an 
outside 
observer of, 
one s mental processes or 
body (e.g., 
feeling 
as though 
one 
were 
in 
a 
dream; 
feeling 
a 
sense 
of 
unreality 
of 
self 
or body or of 
time 
moving 
slowly). 
2. 
Derealization: 
Persistent 
or recurrent 
experiences of 
unreality of 
surroundings 
(e.g., 
the 
world 
around 
the 
individual is experienced 
as unreal, 
dreamlike, 
distant, 
or distorted). 
Note: 
To 
use 
this subtype, 
the 
dissociative 
symptoms must 
not 
be 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
blackouts) or another medical 
condition 
(e.g., 
complex partial seizures). 


Specify 
if: 
With 
delayed 
expression: 
If 
the 
full diagnostic criteria 
are 
not 
met 
until at 
least 
6 
months after the 
event 
(although 
the 
onset 
and 
expression 
of 
some 
symptoms 
may be 
immediate). 


305 


Diagnostic Features 


The essential 
feature of posttraumatic stress disorder (PTSD) is the development 
of characteristic 
symptoms following exposure to one or more traumatic events. The clinical 
presentation of 
PTSD varies. In some individuals, fear-based reexperiencing, emotional, and behavioral 
symptoms may predominate. In others, anhedonic or dysphoric mood states and negative 
cognitions may be most 
prominent. In some other individuals, arousal 
and reactive-externalizing 
symptoms are prominent, while in yet 
others, dissociative symptoms predominate. Finally, some 
individuals exhibit combinations of these symptom patterns. 


The following discussion of specific criteria for PTSD refers to specific criteria for adults; 
criteria for children 6 years or younger may differ in criterion numbering given differences in 
applicable criteria for this age group. 


The traumatic events in Criterion A all 
involve actual 
or threatened death, serious injury, or 
sexual 
violence in some way but 
differ in how the individual 
is exposed to them, which can be 
through directly experiencing the traumatic event 
(Criterion A1), witnessing in person the event 
as it 
occurred to others (Criterion A2), learning that 
the event 
occurred to a family member or a 
close friend (Criterion A3), or indirect 
exposure in the course of occupational 
duties, through 
being exposed to grotesque details of an event 
(Criterion A4). The disorder may be especially 
severe or long-lasting when the stressor is interpersonal 
and intentional 
(e.g., torture, sexual 
violence). 


The directly experienced traumatic events in Criterion A include, but 
are not 
limited to, 
exposure to war as a combatant 
or civilian, actual 
or threatened physical 
assault 
in which the 
threat 
is perceived as imminent 
and realistic (e.g., physical 
attack, robbery, mugging, childhood 
physical 
abuse), being kidnapped, being taken hostage, terrorist 
attack, torture, incarceration as a 
prisoner of war, natural or human-made disasters, and severe motor vehicle accidents. 


Sexual 
trauma includes, but 
is not 
limited to, actual 
or threatened sexual 
violence or coercion 



(e.g., forced sexual 
penetration; 
alcohol/drug-facilitated nonconsensual 
sexual 
penetration; 
other 
unwanted sexual 
contact; 
and other unwanted sexual 
experiences not 
involving contact, such as 
being forced to watch pornography, exposure to the display of genitals by an exhibitionist, or 
being the victim 
of unwanted photography or videotaping of a sexual 
nature or the unwanted 
dissemination of these photographs or videos). 


Being bullied may qualify as a Criterion A1 experience when there is a credible threat 
of 
serious harm 
or sexual 
violence. For children, sexually violent 
events may include 
developmentally inappropriate sexual experiences without physical violence or injury. 


A life-threatening illness or debilitating medical 
condition is not 
necessarily considered a 
traumatic event. Qualifying events of this type include life-threatening medical 
emergencies 
(e.g., an acute myocardial 
infarction, anaphylactic shock) or a particular event 
in treatment 
that 
evokes catastrophic feelings of terror, pain, helplessness, or imminent 
death (e.g., waking during 
surgery, debridement of severe burn wounds, emergency cardioversion). 


Witnessed events (Criterion A2) include, but 
are not 
limited to, observing threatened or 
serious injury, unnatural 
death, physical 
or sexual 
abuse of another person due to violent 
assault, 
domestic violence, accident, war, or disaster. For example, this would include parents witnessing 
their child in an acute life-endangering incident 
(e.g., a diving accident) or a medical 
catastrophe 
during the course of their child s illness or ongoing treatment 
(e.g., a life-threatening 
hemorrhage). 


Indirect 
exposure through learning about 
an event 
(Criterion A3) is limited to events 
affecting close relatives or friends that 
were violent 
or accidental 
(i.e., death from 
natural 
causes 
does not 
qualify). Such events include murder, violent 
personal 
assault, combat, terrorist 
attack, 
sexual violence, suicide, and serious accident or injury. 


The indirect 
exposure of professionals to the grotesque effects of war, rape, genocide, or 
abusive violence inflicted on others occurring in the context 
of their work duties can also result 
in PTSD and thus is considered to be a qualifying trauma (Criterion A4). Examples 


306 


include first 
responders exposed to serious injury or death and military personnel 
collecting 
human remains. Indirect 
exposure can also occur through photos, videos, verbal 
accounts, or 
written accounts (e.g., police officers reviewing crime reports or conducting interviews with 
crime victims, drone operators, members of the news media covering traumatic events, and 
psychotherapists exposed to details of their patients  traumatic experiences). 


Exposure to multiple traumatic events is common and can take many forms. Some 
individuals experience different 
types of traumatic events at 
different 
times (e.g., sexual 
violence 
during childhood and natural 
disaster as adults). Others experience the same type of traumatic 
event 
at 
different 
times or in a series committed by the same person/people over an extended 
period (e.g., child sexual 
or physical 
assault; 
physical 
or sexual 
assault 
by an intimate partner). 
Others may experience numerous traumatic events that 
are the same or different 
during an 
extended hazardous period such as deployment 
or living in a conflict 
zone. When one is 
assessing the PTSD criteria in individuals who have experienced multiple traumatic events 
across their lives, it 
may be useful 
to determine if there is a specific, discrete example that 
the 
individual 
considers to be the worst 
given that 
the symptomatic expressions of PTSD Criterion B 
and Criterion C 
specifically refer to the traumatic event 
(e.g., recurrent, involuntary, and 



intrusive distressing recollections of the traumatic event). However, if it 
is difficult 
for the 
individual 
to identify a worst 
example, it 
is appropriate to consider the entire exposure as 
meeting Criterion A. In addition, some discrete events may incorporate several 
traumatic event 
types (e.g., an individual 
involved in a mass casualty incident 
sustains a major injury, witnesses 
someone else being injured, and then learns that a family member was killed in the incident). 


The traumatic event 
can be reexperienced in various ways. Commonly, the individual 
has 
recurrent, involuntary, and intrusive recollections of the event 
(Criterion B1). Intrusive 
recollections in PTSD are distinguished from 
depressive rumination in that 
they apply only to 
involuntary and intrusive distressing memories. The emphasis is on recurrent 
memories of the 
event 
that 
usually include intrusive, vivid, sensory, and emotional 
components that 
are 
distressing and not 
merely ruminative. A common reexperiencing symptom 
is distressing dreams 
that 
replay the event 
itself or that 
are representative or thematically related to the major threats 
involved in the traumatic event 
(Criterion B2). The individual 
may experience dissociative states 
that 
typically last 
a few seconds and rarely are of a longer duration, during which components of 
the event 
are relived and the individual 
behaves as if the event 
were occurring at 
that 
moment 
(Criterion B3). Such events occur on a continuum, ranging from 
brief visual 
or other sensory 
intrusions about 
part 
of the traumatic event 
without 
loss of reality orientation to a partial 
loss of 
awareness of present 
surroundings to a complete loss of awareness. These episodes, often 
referred to as  flashbacks,  are typically brief but 
can be associated with prolonged distress and 
heightened arousal. For young children, reenactment 
of events related to trauma may be 
expressed behaviorally in play or in dissociative states. Intense psychological 
distress (Criterion 
B4) or physiological 
reactivity (Criterion B5) often occurs when the individual 
is exposed to 
triggering events or somatic reactions that 
resemble or symbolize an aspect 
of the traumatic 
event 
(e.g., windy days after a hurricane, seeing someone who resembles one s perpetrator). The 
triggering cue could also be a physical 
sensation (e.g., dizziness for survivors of head trauma, 
rapid heartbeat 
for a previously traumatized child), particularly for individuals with highly 
somatic presentations. 


Stimuli 
associated with the trauma are persistently avoided. The individual 
commonly makes 
deliberate efforts to avoid thoughts, memories, or feelings (e.g., by utilizing distraction or 
suppression techniques, including substance use, to avoid internal 
reminders) (Criterion C1), and 
to avoid activities, conversations, objects, situations, or people who arouse recollections of it 
(Criterion C2). 


Negative alterations in cognitions or mood associated with the traumatic event 
begin or 
worsen after exposure to the event. These negative alterations can take various forms, including 
an inability to remember key and emotionally painful aspects of the traumatic 


307 


event. Such memory loss is typically attributable to dissociative amnesia and is not 
attributable to head injury or impaired encoding of the memory due to drug or alcohol 
use 
(Criterion D1). Individuals with PTSD often report 
that 
the traumatic event 
has irrevocably 
altered their lives and their view of the world. This is characterized by persistent 
and exaggerated 
negative beliefs and expectations regarding important 
aspects of life applied to themselves, 
others, the world, or the future (Criterion D2) (e.g.,  Bad things will 
always happen to me ; 
 The 
world is dangerous, and I can never be adequately protected ; 
 I can t 
trust 
anyone ever again ; 



 My life is permanently ruined ; 
 I have lost 
any chance for future happiness ; 
 My life will 
be 
cut 
short ). Individuals with PTSD may have persistent 
erroneous cognitions about 
the causes of 
the traumatic event 
that 
lead them 
to blame themselves or others (e.g.,  It s all 
my fault 
that 
my 
uncle abused me ) (Criterion D3). A persistent 
negative mood state (e.g., fear, dysphoria, horror, 
anger, guilt, shame) either began or worsened after exposure to the event 
(Criterion D4). The 
individual 
may experience markedly diminished interest 
or participation in previously enjoyed 
activities (Criterion D5), may feel 
detached or estranged from 
other people (Criterion D6), or 
may experience a persistent 
inability to feel 
positive emotions (especially happiness, joy, 
satisfaction, or emotions associated with intimacy, tenderness, and sexuality) (Criterion D7). 


Negative alterations in arousal 
and reactivity also begin or get 
worse after exposure to the 
event. Individuals with PTSD may exhibit 
irritable or angry behavior and may engage in 
aggressive verbal 
or physical 
behavior with little or no provocation (e.g., yelling at 
people, 
getting into fights, destroying objects) (Criterion E1). They may also engage voluntarily in 
reckless or self-destructive behavior that 
is dangerous, that 
shows a disregard for the physical 
safety of themselves or others, and that 
could directly result 
in serious physical 
harm 
or death 
(Criterion E2). Examples include, but 
are not 
limited to, dangerous driving (e.g., drunk driving, 
driving at 
dangerously high speeds), excessive alcohol 
or drug use, having risky sex (e.g., 
unprotected sex with a partner whose HIV status is unknown, high number of sexual partners), or 
self-directed violence including suicidal 
behaviors. Criterion E2 does not 
include circumstances 
in which individuals must 
engage in dangerous situations as a part 
of their job (e.g., armed forces 
members in combat 
situations or first 
responders in emergency situations) and take reasonable 
safety precautions to reduce their risk or when individuals engage in behaviors that 
may be 
unwise, unhealthy, or financially harmful 
but 
pose no direct 
risk of immediate serious physical 
harm 
or death (e.g., pathological 
gambling, poor financial 
decisions, binge eating, unhealthy 
lifestyles). PTSD is often characterized by a heightened vigilance for potential 
threats, including 
those that 
are related to the traumatic experience (e.g., following a motor vehicle accident, being 
especially sensitive to the threat 
potentially caused by cars or trucks) and those not 
related to the 
traumatic event 
(e.g., being fearful 
of suffering a heart 
attack) (Criterion E3). Individuals with 
PTSD may be very reactive to unexpected stimuli, displaying a heightened startle response, or 
jumpiness, to loud noises or unexpected movements (e.g., jumping markedly in response to a 
telephone ringing) (Criterion E4). Startle responses are involuntary and reflexive (automatic, 
instantaneous), and stimuli 
that 
evoke exaggerated startle responses (Criterion E4) need not 
be 
related at 
all 
to the traumatic event. Startle responses are distinguished from 
the cued 
physiological 
arousal 
responses in Criterion B5, for which there needs to be at 
least 
some level 
of conscious appraisal 
that 
the stimulus producing physiological 
responses is related to the 
trauma. Concentration difficulties, including difficulty remembering daily events (e.g., forgetting 
one s telephone number) or attending to focused tasks (e.g., following a conversation for a 
sustained period of time), are commonly reported (Criterion E5). Problems with sleep onset 
and 
maintenance are common and may be associated with nightmares and safety concerns or with 
generalized elevated arousal that interferes with adequate sleep (Criterion E6). 


The diagnosis of PTSD requires that 
the duration of the symptoms in Criteria B, C, D, and E 
be more than 1 month (Criterion F). For a current 
diagnosis of PTSD, Criteria B, C, D, and E 
must all be met for more than 1 month, for at least the past month. For a lifetime 


308 



diagnosis of PTSD, there must 
be a period of time lasting more than 1 month during which 
Criteria B, C, D, and E have all been met for the same 1-month period of time. 


A significant 
subgroup of individuals with PTSD experience persistent 
dissociative 
symptoms of either depersonalization (detachment 
from 
their bodies) or derealization 
(detachment 
from 
the world around them). This can be indicated by using the  with dissociative 
symptoms  specifier. 


Associated Features 


Developmental 
regression, such as loss of language in young children, may occur. Auditory 
pseudo-hallucinations, such as having the sensory experience of hearing one s thoughts spoken 
in one or more different 
voices, as well 
as paranoid ideation, can be present. Following 
prolonged, repeated, and severe traumatic events (e.g., childhood abuse, torture), the individual 
may additionally experience difficulties in regulating emotions or maintaining stable 
interpersonal 
relationships, or dissociative symptoms. When the traumatic event 
involves the 
violent 
death of someone with whom 
the individual 
had a close relationship, symptoms of both 
prolonged grief disorder and PTSD may be present. 


Prevalence 


The national 
lifetime prevalence estimate for PTSD using DSM-IV criteria is 6.8% for U.S. 
adults. Lifetime prevalence for U.S. adolescents using DSM-IV criteria has ranged from 
5.0% to 
8.1% and a past 
6-month prevalence of 4.9% for adolescents. While definitive, comprehensive 
population-based data using DSM-5 are not 
available, findings are beginning to emerge. In two 


U.S. national 
epidemiological 
studies, lifetime DSM-5 PTSD prevalence estimates ranged from 
6.1% to 8.3%, and the national 
12-month DSM-5 prevalence estimate was 4.7% in both studies. 
National 
lifetime DSM-IV PTSD estimates from 
World Mental 
Health Surveys in 24 countries 
varied substantially among countries, income country groups, and WHO regions but 
was 3.9% 
overall. In conflict-affected populations worldwide, the point 
prevalence of PTSD with 
functional impairment is 11% after adjustment for age differences across studies. 
Rates of PTSD are higher among veterans and others whose vocation increases the risk of 
traumatic exposure (e.g., police, firefighters, emergency medical 
personnel). Highest 
rates 
(ranging from 
one-third to more than one-half of those exposed) are found among survivors of 
rape, military combat 
and captivity, and ethnically or politically motivated internment 
and 
genocide. The prevalence of PTSD may vary across development; 
children and adolescents, 
including preschool 
children, generally have displayed lower prevalence following exposure to 
serious traumatic events; 
however, this may be because previous criteria were insufficiently 
developmentally informed. Racial 
differences, based on DSM-IV data, show higher rates of 
PTSD among U.S. Latinx, African Americans, and American Indians compared with Whites. 
Potential 
reasons for these prevalence variations include differences in predisposing or enabling 
factors, such as exposure to past 
adversity and racism 
and discrimination, and in availability or 
quality of treatment, social 
support, socioeconomic status, and other social 
resources that 
facilitate recovery and are confounded with ethnic and racialized background. 


Development and Course 



PTSD can occur at 
any age, beginning after the first 
year of life. Symptoms usually begin within 
the first 
3 months after the trauma, although there may be a delay of months, or even years, 
before full 
criteria for the diagnosis are met. There is abundant 
evidence for what 
DSM-IV called 
 delayed onset  but 
is now called  delayed expression,  with the recognition that 
some 
symptoms typically appear immediately and that the delay is in meeting full criteria. 


Frequently, an individual s reaction to a trauma initially meets criteria for acute stress 
disorder in the immediate aftermath of the trauma. The symptoms of PTSD and the 


309 


relative predominance of different 
symptoms may vary over time. Duration of the symptoms 
also varies, with complete recovery within 3 months occurring in approximately one-half of 
adults, while some individuals remain symptomatic for longer than 12 months and sometimes for 
more than 50 years. Symptom 
recurrence and intensification may occur in response to reminders 
of the original trauma, ongoing life stressors, or newly experienced traumatic events. 


The clinical 
expression of reexperiencing can vary across development. Developmental 
variations in clinical 
expression inform 
the use of different 
criteria in children 6 years and 
younger and in individuals who are older. Young children may report 
new onset 
of frightening 
dreams without 
content 
specific to the traumatic event. Children age 6 and younger may develop 
PTSD as a result 
of severe emotional 
abuse (e.g., threat 
of abandonment), which can be 
perceived as life-threatening. During treatment 
for life-threatening illness (e.g., cancer, solid 
organ transplantation), the experience of young children of the severity and intensity of the 
treatment 
may contribute to risk of developing posttraumatic stress symptoms; 
the self-appraisal 
of threat 
may also contribute to the risk of developing posttraumatic stress symptoms in 
adolescents. Before age 6 years, young children are more likely to express reexperiencing 
symptoms through play that 
refers directly or symbolically to the trauma (see PTSD criteria for 
children 6 years and younger). They may not 
manifest 
fearful 
reactions at 
the time of the 
exposure or during reexperiencing. Parents may report 
a wide range of emotional 
or behavioral 
changes in young children. Children may focus on imagined interventions in their play or 
storytelling. In addition to avoidance, children may become preoccupied with reminders. 
Because of young children s limitations in expressing thoughts or labeling emotions, negative 
alterations in mood or cognition tend to involve primarily mood changes. Children may 
experience co-occurring traumas (e.g., physical 
abuse, witnessing domestic violence) and in 
chronic circumstances may not 
be able to identify onset 
of symptomatology. Avoidant 
behavior 
may be associated with restricted play or exploratory behavior in young children; 
reduced 
participation in new activities in school-age children; 
or reluctance to pursue developmental 
opportunities in adolescents (e.g., dating, driving). Older children and adolescents may judge 
themselves as cowardly. Adolescents may harbor beliefs of being changed in ways that 
make 
them 
socially undesirable and estrange them 
from 
peers and lose aspirations for the future. 
Irritable or aggressive behavior in children and adolescents can interfere with peer relationships 
and school 
behavior. Reckless behavior may lead to accidental 
injury to self or others, thrill-
seeking, or high-risk behaviors. In older individuals, the disorder is associated with negative 
health perceptions, primary care utilization, and suicidal 
thoughts. In addition, declining health, 
worsening cognitive functioning, and social isolation may exacerbate PTSD symptoms. 



Risk and Prognostic Factors 


Risk factors for PTSD can operate in many ways, including predisposing individuals to trauma 
or to extreme emotional 
responses when exposed to traumatic events. Risk (and protective) 
factors are generally divided into pretraumatic, peritraumatic, and posttraumatic factors. 


Pretraumatic 
Factors 
Temperamental. 
High-risk factors include childhood emotional 
problems by age 6 years (e.g., 
externalizing or anxiety problems) and prior mental 
disorders (e.g., panic disorder, depressive 
disorder, PTSD, or obsessive-compulsive disorder [OCD]). Individual 
differences in premorbid 
personality may influence the trajectory of response to trauma and treatment 
outcomes. 
Personality traits associated with negative emotional 
responses such as depressed mood and 
anxiousness represent 
risk factors for the development 
of PTSD. Such traits might 
be captured in 
measures of negative affectivity (neuroticism) on 


310 


standardized personality scales. Premorbid trait 
impulsivity tends to be associated with 
externalizing manifestations of PTSD and comorbidities of the externalizing spectrum, including 
substance use disorder or aggressive behavior. 


Environmental. 
As documented among U.S. civilians and veterans, these risk factors include 
lower socioeconomic status; 
lower education; 
exposure to prior trauma (especially during 
childhood); 
childhood adversity (e.g., economic deprivation, family dysfunction, parental 
separation or death); 
lower intelligence; 
ethnic discrimination and racism; 
and a family 
psychiatric history. Social support prior to event exposure is protective. 


Genetic 
and 
physiological. 
The risk of developing PTSD following traumatic exposure has been 
demonstrated to be modestly heritable in twin studies and molecular studies. Genome-wide 
association data from 
a large multiethnic cohort 
support 
the heritability of PTSD and 
demonstrate three robust 
genome-wide significant 
loci 
that 
vary by geographic ancestry. 
Susceptibility to PTSD may also be influenced by epigenetic factors. Genome-wide association 
data from 
U.S. veterans identify eight 
significant 
regions in Americans of European descent 
associated with intrusive reexperiencing symptoms of PTSD; 
data from 
the United Kingdom 
also 
support these associations. 


Peritraumatic 
Factors 
Environmental. 
These include severity (dose) of the trauma, perceived life threat, personal 
injury, 
interpersonal 
violence (particularly trauma perpetrated by a caregiver or involving a witnessed 
threat 
to a caregiver in children), and, for military personnel, being a perpetrator, witnessing 
atrocities, or killing the enemy. Finally, dissociation, fear, panic, and other peritraumatic 
responses that occur during the trauma and persist afterward are risk factors. 


Posttraumatic 
Factors 
Temperamental. 
These include negative appraisals, inappropriate coping strategies, and 
development of acute stress disorder. 



Environmental. 
These include subsequent 
exposure to repeated upsetting reminders, subsequent 
adverse life events, and financial 
or other trauma-related losses. Posttraumatic experiences such 
as forced migration and high levels of daily stressors may contribute to different conditional risks 
of PTSD across cultural 
contexts. Exposure to racial 
and ethnic discrimination has been 
associated with a more chronic course among African American and Latinx adults. Social 
support 
(including family stability, for children) is a protective factor that 
moderates outcome 
after trauma. 


Culture-Related Diagnostic Issues 


Different 
demographic, cultural, and occupational 
groups have different 
levels of exposure to 
traumatic events, and the relative risk of developing PTSD following a similar level 
of exposure 
(e.g., religious persecution) may also vary across cultural, ethnic, and racialized groups. 
Variation in the type of traumatic exposure (e.g., genocide), the impact 
on disorder severity of 
the meaning attributed to the traumatic event 
(e.g., inability to perform 
funerary rites after a mass 
killing), the ongoing sociocultural 
context 
(e.g., residing among unpunished perpetrators in 
postconflict 
settings), exposure to racial 
and ethnic discrimination, and other cultural 
factors 
(e.g., acculturative stress in migrants) may influence the risk of onset 
and severity of PTSD 
across cultural 
groups. Some communities are exposed to pervasive and ongoing traumatic 
environments, rather than isolated Criterion A events; in these communities, the predictive power 
of individual 
traumatic events for the development 
of PTSD may diminish. In cultures where 
social 
image (e.g., maintaining a family s  face ) is emphasized, public defamation or shaming 
may magnify the impact 
of Criterion A events. Some cultures may attribute PTSD syndromes to 
negative supernatural experiences. 


311 


The clinical 
expression of the symptoms or symptom 
clusters of PTSD can vary culturally in 
both adults and children. In many non-Western groups, avoidance is less commonly observed, 
whereas somatic symptoms (e.g., dizziness, shortness of breath, heat 
sensations) are more 
common; 
other symptoms that 
vary cross-culturally are distressing dreams, amnesia not 
related 
to head injury, and reckless but 
nonsuicidal 
behavior. Negative moods, especially anger, are 
common cross-culturally in individuals with PTSD, as are distressing dreams and sleep paralysis. 
Across cultures, somatic symptoms are frequent, occurring in both children and adults, especially 
after sexual 
trauma. Symptoms that 
vary cross-culturally in relation to PTSD among children 
include intrusive thoughts, diminished participation in activities, inability to experience positive 
emotions, irritability, aggression, and hypervigilance. Distressing dreams, flashbacks, 
psychological 
distress upon exposure to trauma cues, and efforts to avoid memories and thoughts 
are common in children with PTSD across cultures. 


In certain cultural 
contexts, it 
may be normative to respond to traumatic events with negative 
beliefs about 
oneself or with spiritual 
attributions that 
may appear exaggerated to others. For 
example, blaming oneself may be consistent 
with ideas of karma in South and East 
Asia, destiny 
or  spoiled medicine law  in West 
Africa, and cultural 
differences in locus of control 
and 
conceptions of self. 


In many populations around the world, there are cultural 
concepts of distress that 
resemble 



PTSD and are characterized by diverse manifestations of psychological 
distress attributed to 
frightening or traumatic experiences. Thus, cultural 
concepts of distress influence the expression 
of PTSD and the range of its comorbid disorders (see  Culture and Psychiatric Diagnosis  in 
Section III). 


Sex- and Gender-Related Diagnostic Issues 


PTSD is more prevalent 
among women than among men across the life span. Lifetime 
prevalence of PTSD ranges from 
8.0% to 11.0% for women and 4.1% to 5.4% for men based on 
two large U.S. population-based studies using DSM-5 criteria. Some of the increased risk for 
PTSD in women appears to be attributable to a greater likelihood of exposure to childhood 
sexual 
abuse, sexual 
assault, and other forms of interpersonal 
violence, which carry the highest 
risk for development 
of PTSD. Women in the general 
population also experience PTSD for a 
longer duration than do men. However, other factors likely contributing to the higher prevalence 
in women include gender differences in the emotional 
and cognitive processing of trauma, as 
well 
as effects of reproductive hormones. When responses of men and women to specific 
stressors are compared, gender differences in risk for PTSD persist. On the other hand, PTSD 
symptom profiles and factor structures are similar between men and women. 


Association With Suicidal 
Thoughts or Behavior 


Traumatic events such as childhood abuse or sexual 
trauma increase an individual s suicide risk 
in both civilians and veterans. PTSD is associated with suicidal 
thoughts, suicide attempts, and 
death from 
suicide. The presence of PTSD has been associated with an increased likelihood of 
transitioning from 
suicidal 
thoughts to a suicide plan or attempt, and this effect 
of PTSD occurs 
independently of the increased risk of mood disorders on the likelihood of suicidal 
behaviors. 
Among adolescents there is also a significant 
relationship between PTSD and suicidal 
thoughts 
or behavior even after adjustment for the effects of comorbidity. 


Functional 
Consequences of Posttraumatic Stress Disorder 


PTSD is associated with high impairment 
in social, occupational, and physical 
functioning; 
reduced quality of life; and physical health problems. Impaired functioning is exhibited 


312 


across social, interpersonal, developmental, educational, physical 
health, and occupational 
domains. In community and veteran samples, PTSD is associated with poor social 
and family 
relationships, absenteeism 
from 
work, lower income, and lower educational 
and occupational 
success. 


Differential 
Diagnosis 


Adjustment 
disorders. 
In adjustment 
disorders, the stressor can be of any severity or type rather 
than a stressor involving exposure to actual or threatened death, serious injury, or sexual violence 
as required by PTSD Criterion A. The diagnosis of an adjustment 
disorder is used when the 
response to a stressor that 
meets PTSD Criterion A does not 
meet 
all 
other PTSD criteria (or 



criteria for another mental 
disorder). An adjustment 
disorder is also diagnosed when the 
symptom 
pattern of PTSD occurs in response to a stressor that 
does not 
meet 
PTSD Criterion A 
(e.g., spouse leaving, being fired). 


Other posttraumatic 
disorders 
and 
conditions. 
Not 
all 
psychopathology that 
occurs in individuals 
exposed to an extreme stressor should necessarily be attributed to PTSD. The PTSD diagnosis 
requires that 
trauma exposure precede the onset 
or exacerbation of pertinent 
symptoms. If the 
symptom 
response pattern to the extreme stressor meets criteria for another mental 
disorder, 
these diagnoses should be given instead of, or in addition to, PTSD. Other diagnoses and 
conditions are excluded if they are better explained by PTSD (e.g., symptoms of panic disorder 
that 
occur only after exposure to traumatic reminders). If severe, symptom 
response patterns to 
the extreme stressor that 
meet 
criteria for another mental 
disorder may warrant 
a separate 
diagnosis (e.g., dissociative amnesia) in addition to PTSD. 


Acute 
stress 
disorder. 
Acute stress disorder is distinguished from 
PTSD because the symptom 
pattern in acute stress disorder is restricted to a duration of 3 days to 1 month following exposure 
to the traumatic event. 
Anxiety 
disorders 
and 
obsessive-compulsive 
disorder. 
In OCD, there are recurrent intrusive thoughts, 


but 
these meet 
the definition of an obsession. In addition, the intrusive thoughts are not 
related to 
an experienced traumatic event, compulsions are usually present, and other symptoms of PTSD 
or acute stress disorder are typically absent. Neither the arousal 
and dissociative symptoms of 
panic disorder nor the avoidance, irritability, and anxiety of generalized anxiety disorder are 
associated with a specific traumatic event. The symptoms of separation anxiety disorder are 
clearly related to separation from home or family, rather than to a traumatic event. 


Major depressive 
disorder. 
Major depression may or may not 
be preceded by a traumatic event 
and 
should be diagnosed if full 
criteria have been met. Specifically, major depressive disorder does 
not 
include any PTSD Criterion B 
or C 
symptoms. Nor does it 
include a number of symptoms 
from 
PTSD Criterion D or E. However, if full 
criteria for PTSD are also met, both diagnoses 
may be given. 


Attention-deficit/hyperactivity 
disorder. 
Both ADHD and PTSD may include problems in attention, 
concentration, and learning. In contrast 
to ADHD, where the problems in attention, 
concentration, and learning must 
have their onset 
prior to age 12, in PTSD the symptoms have 
their onset 
following exposure to a Criterion A traumatic event. In PTSD, disruptions in the 
individual s attention and concentration can be attributable to alertness to danger and 
exaggerated startle responses to reminders of the trauma. 


Personality 
disorders. 
Interpersonal 
difficulties that 
had their onset, or were greatly exacerbated, 
after exposure to a traumatic event 
may be an indication of PTSD, rather than a personality 
disorder, in which such difficulties would be expected independently of any traumatic exposure. 


313 


Dissociative 
disorders. 
Dissociative amnesia, dissociative identity disorder, and 
depersonalization-derealization disorder may or may not 
be preceded by exposure to a traumatic 
event 
or may or may not 
have co-occurring PTSD symptoms. When full 
PTSD criteria are also 
met, however, the PTSD  with dissociative symptoms  subtype should be considered. 



Functional 
neurological 
symptom disorder (conversion 
disorder). 
New onset 
of somatic symptoms 


within the context 
of posttraumatic distress might 
be an indication of PTSD rather than 
functional neurological symptom disorder. 
Psychotic 
disorders. 
Flashbacks in PTSD must 
be distinguished from 
illusions, hallucinations, 


and other perceptual 
disturbances that 
may occur in schizophrenia, brief psychotic disorder, and 
other psychotic disorders; 
depressive and bipolar disorders with psychotic features; 
delirium; 
substance/medication-induced disorders; 
and psychotic disorders due to another medical 
condition. PTSD flashbacks are distinguished from 
these other perceptual 
disturbances by being 
directly related to the traumatic experience and by occurring in the absence of other psychotic or 
substance-induced features. 


Traumatic 
brain 
injury. 
Some types of traumatic events increase risk of both PTSD and traumatic 
brain injury (TBI) because they can produce head injuries (e.g., military combat, bomb blasts, 
child physical 
abuse, intimate partner violence, violent 
crime, motor vehicle or other accidents). 
In such cases, individuals presenting with PTSD may also have TBI, and those presenting with 
TBI may also have PTSD. Individuals with PTSD who also have TBI may have persistent 
postconcussive symptoms (e.g., headaches, dizziness, sensitivity to light 
or sound, irritability, 
concentration deficits). However, such symptoms may also occur in non-brain-injured 
populations, including individuals with PTSD. Because symptoms of PTSD and TBI-related 
neurocognitive symptoms can overlap, a differential 
diagnosis between PTSD and 
neurocognitive disorder symptoms attributable to TBI may be possible based on the presence of 
symptoms that 
are distinctive to each presentation. Whereas reexperiencing and avoidance are 
characteristic of PTSD and not 
the effects of TBI, persistent 
disorientation and confusion are 
more specific to TBI (neurocognitive effects) than to PTSD. TBI-related memory problems 
concerning the traumatic event 
are typically attributable to injury-related inability to encode the 
information, whereas PTSD-related memory problems typically reflect 
dissociative amnesia. 
Sleep difficulties are common to both disorders. 


Comorbidity 


Individuals with PTSD are more likely than those without 
PTSD to have symptoms that 
meet 
diagnostic criteria for at 
least 
one other mental 
disorder, such as depressive, bipolar, anxiety, or 
substance use disorders. PTSD is also associated with increased risk of major neurocognitive 
disorder. In a U.S.-based study, women were more likely to develop PTSD following a mild TBI. 
Although most 
young children with PTSD also have at 
least 
one other diagnosis, the patterns of 
comorbidity are different 
than in adults, with oppositional 
defiant 
disorder and separation anxiety 
disorder predominating. 


Acute Stress Disorder 


Diagnostic Criteria 
F43.0 
A. 
Exposure 
to 
actual or threatened 
death, 
serious injury, 
or sexual violence 
in 
one 
(or more) of 
the 
following 
ways: 



1. 
Directly experiencing 
the 
traumatic event(s). 
2. 
Witnessing, 
in 
person, 
the 
event(s) as it 
occurred 
to 
others. 
314 


3. 
Learning 
that 
the 
event(s) occurred 
to 
a 
close 
family member or close 
friend. 
Note: 
In 
cases of 
actual or threatened 
death 
of 
a 
family member or friend, 
the 
event(s) must 
have 
been 
violent 
or accidental. 
4. 
Experiencing 
repeated 
or extreme 
exposure 
to 
aversive 
details of 
the 
traumatic event(s) (e.g., 
first 
responders collecting 
human 
remains, 
police 
officers repeatedly exposed 
to 
details of 
child 
abuse). 
Note: 
This does not 
apply to 
exposure 
through 
electronic media, 
television, 
movies, 
or pictures, 
unless this exposure 
is work related. 


B. 
Presence 
of 
nine 
(or more) of 
the 
following 
symptoms from any of 
the 
five 
categories of 
intrusion, 
negative 
mood, 
dissociation, 
avoidance, 
and 
arousal, 
beginning 
or worsening 
after the 
traumatic event(s) occurred: 
Intrusion 
Symptoms 


1. 
Recurrent, 
involuntary, 
and 
intrusive 
distressing 
memories of 
the 
traumatic 
event(s). 
Note: 
In 
children, 
repetitive 
play may occur in 
which 
themes or 
aspects of 
the 
traumatic event(s) are 
expressed. 
2. 
Recurrent 
distressing 
dreams in 
which 
the 
content 
and/or affect 
of 
the 
dream 
are 
related 
to 
the 
event(s). 
Note: 
In 
children, 
there 
may be 
frightening 
dreams 
without 
recognizable 
content. 
3. 
Dissociative 
reactions (e.g., 
flashbacks) in 
which 
the 
individual feels or acts 
as if 
the 
traumatic event(s) were 
recurring. 
(Such 
reactions may occur on 
a 
continuum, 
with 
the 
most 
extreme 
expression 
being 
a 
complete 
loss of 
awareness of 
present 
surroundings.) Note: 
In 
children, 
trauma-specific 
reenactment 
may occur in 
play. 
4. 
Intense 
or prolonged 
psychological distress or marked 
physiological reactions 
in 
response 
to 
internal or external cues that 
symbolize 
or resemble 
an 
aspect 
of 
the 
traumatic event(s). 
Negative 
Mood 


5. 
Persistent 
inability to 
experience 
positive 
emotions (e.g., 
inability to 
experience 
happiness, 
satisfaction, 
or loving 
feelings). 
Dissociative 
Symptoms 


6. 
An 
altered 
sense 
of 
the 
reality of 
one s surroundings or oneself 
(e.g., 
seeing 
oneself 
from another s perspective, 
being 
in 
a 
daze, 
time 
slowing). 
7. 
Inability to 
remember an 
important 
aspect 
of 
the 
traumatic event(s) (typically 
due 
to 
dissociative 
amnesia 
and 
not 
to 
other factors such 
as head 
injury, 
alcohol, 
or drugs). 
Avoidance 
Symptoms 



8. 
Efforts to 
avoid 
distressing 
memories, 
thoughts, 
or feelings about 
or closely 
associated 
with 
the 
traumatic event(s). 
9. 
Efforts to 
avoid 
external reminders (people, 
places, 
conversations, 
activities, 
objects, 
situations) that 
arouse 
distressing 
memories, 
thoughts, 
or feelings 
about 
or closely associated 
with 
the 
traumatic event(s). 
Arousal 
Symptoms 


10. 
Sleep 
disturbance 
(e.g., 
difficulty falling 
or staying 
asleep, 
restless sleep). 
11. 
Irritable 
behavior and 
angry outbursts (with 
little 
or no 
provocation), 
typically 
expressed 
as verbal or physical aggression 
toward 
people 
or objects. 
12. 
Hypervigilance. 
13. 
Problems with 
concentration. 
14. 
Exaggerated 
startle 
response. 
315 


C. 
Duration 
of 
the 
disturbance 
(symptoms in 
Criterion 
B) is 3 
days to 
1 
month 
after 
trauma 
exposure. 
Note: 
Symptoms typically begin 
immediately after the 
trauma, 
but 
persistence 
for at 
least 
3 
days and 
up 
to 
a 
month 
is needed 
to 
meet 
disorder criteria. 


D. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
E. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
medication 
or alcohol) or another medical condition 
(e.g., 
mild 
traumatic 
brain 
injury) and 
is not 
better explained 
by brief 
psychotic disorder. 
Diagnostic Features 


The essential 
feature of acute stress disorder is the development 
of characteristic symptoms 
lasting from 
3 days to 1 month following exposure to one or more traumatic events (Criterion A), 
which are the same type as described in PTSD Criterion A (for more information, see 
 Diagnostic Features  for PTSD). 


The clinical 
presentation of acute stress disorder may vary by individual 
but 
typically 
involves an anxiety response that 
includes some form 
of reexperiencing of or reactivity to the 
traumatic event. Presentations may include intrusion symptoms, negative mood, dissociative 
symptoms, avoidance symptoms, and arousal 
symptoms (Criterion B1 B14). In some 
individuals, a dissociative or detached presentation can predominate, although these individuals 
typically will 
also display strong emotional 
or physiological 
reactivity in response to trauma 
reminders. In other individuals, there can be a strong anger response in which reactivity is 
characterized by irritable or possibly aggressive responses. 


Intrusion symptoms (Criterion B1 B4) are the same as described in PTSD Criterion B1 B5 
(for discussion of these symptoms, see  Diagnostic Features  for PTSD; 
note that 
acute stress 
disorder Criterion B4 comprises PTSD Criterion B4 and B5). Individuals with acute stress 
disorder may have a persistent 
inability to feel 
positive emotions (e.g., happiness, joy, 



satisfaction, or emotions associated with intimacy, tenderness, sexuality) but 
can experience 
negative emotions such as fear, sadness, anger, guilt, or shame (Criterion B5). Alterations in 
awareness can include depersonalization, 
a detached sense of oneself (e.g., seeing oneself from 
the other side of the room), or derealization, 
having a distorted view of one s surroundings (e.g., 
perceiving that 
things are moving in slow motion, seeing things in a daze, not 
being aware of 
events that 
one would normally encode) (Criterion B6). Some individuals also report 
an inability 
to remember an important 
aspect 
of the traumatic event 
that 
was presumably encoded. This 
symptom 
is attributable to dissociative amnesia and is not 
attributable to head injury, alcohol, or 
drugs (Criterion B7). Stimuli 
associated with the trauma are persistently avoided. The individual 
commonly makes deliberate efforts to avoid thoughts, memories, or feelings (e.g., by using 
distraction or suppression techniques, including substance use, to avoid internal 
reminders) 
(Criterion B8), and to avoid activities, conversations, objects, situations, or people who arouse 
recollections of it (Criterion B9). 


It 
is very common for individuals with acute stress disorder to experience problems with 
sleep onset 
and maintenance, which may be associated with nightmares and safety concerns or 
with generalized elevated arousal 
that 
interferes with adequate sleep (Criterion B10). Individuals 
with acute stress disorder may exhibit 
irritable behavior and may even engage in aggressive 
verbal 
or physical 
behavior with little or no provocation (e.g., yelling at 
people, getting into 
fights, destroying objects) (Criterion B11). Acute stress disorder is often characterized by a 
heightened vigilance for potential 
threats, including those that 
are related to the traumatic 
experience (e.g., following a motor vehicle accident, being especially sensitive to the threat 
potentially caused by cars or trucks) and those not 
related to the traumatic event 
(e.g., being 
fearful 
of suffering a heart 
attack) (Criterion B12). Concentration difficulties (Criterion B13) 
include difficulty remembering familiar facts (e.g., 


316 


forgetting one s telephone number) or daily events (e.g., having recently read part 
of a book 
or newspaper) or attending to focused tasks (e.g., following a conversation for a sustained period 
of time). 


Individuals with acute stress disorder may be very reactive to unexpected stimuli, displaying 
a heightened startle response or jumpiness to loud noises (e.g., in response to a telephone 
ringing) or unexpected movements (Criterion B14). Startle responses are involuntary and 
reflexive (automatic, instantaneous), and stimuli 
that 
evoke exaggerated startle responses 
(Criterion B14) need not be related to the traumatic event. 


The full 
symptom 
picture must 
last 
for at 
least 
3 days after the traumatic event 
but 
should not 
last 
longer than 1 month (Criterion C). Symptoms that 
occur immediately after the event 
but 
resolve in less than 3 days would not meet criteria for acute stress disorder. 


Associated Features 


Individuals with acute stress disorder commonly engage in catastrophic or extremely negative 
thoughts about 
their role in the traumatic event, their response to the traumatic experience, or the 
likelihood of future harm. For example, an individual 
with acute stress disorder may feel 
excessively guilty about 
not 
having prevented the traumatic event 
or about 
not 
adapting to the 



experience more successfully. Individuals with acute stress disorder may also interpret 
their 
symptoms in a catastrophic manner, such that 
flashback memories or emotional 
numbing may be 
interpreted as a sign of diminished mental 
capacity. It 
is common for individuals with acute 
stress disorder to experience panic attacks in the initial 
month after trauma exposure that 
may be 
triggered by trauma reminders or may apparently occur spontaneously. Additionally, individuals 
with acute stress disorder may display chaotic or impulsive behavior. For example, individuals 
may drive recklessly, make irrational 
decisions, or gamble excessively. In children, there may be 
significant 
separation anxiety, possibly manifested by excessive needs for attention from 
caregivers. In the case of bereavement 
following a death that 
occurred in traumatic 
circumstances, the symptoms of acute stress disorder can involve acute grief reactions. In such 
cases, reexperiencing, dissociative, and arousal 
symptoms may involve reactions to the loss, such 
as intrusive memories of the circumstances of the individual s death, disbelief that 
the individual 
has died, and anger about 
the death. Postconcussive symptoms (e.g., headaches, dizziness, 
sensitivity to light 
or sound, irritability, concentration deficits), which occur frequently following 
mild traumatic brain injury (TBI), are also frequently seen in individuals with acute stress 
disorder. Postconcussive symptoms are equally common in brain-injured and non-brain-injured 
populations, and the frequent 
occurrence of postconcussive symptoms could be attributable to 
acute stress disorder symptoms. 


Prevalence 


The prevalence of acute stress disorder in recently trauma-exposed populations (i.e., within 1 
month of trauma exposure) varies according to the nature of the event 
and the context 
in which it 
is assessed. In research conducted in Australia, the United Kingdom, and the United States, acute 
stress disorder was identified in less than 20% of cases following traumatic events that 
do not 
involve interpersonal 
assault for example, motor vehicle accidents, mild TBI, severe burns, and 
industrial 
accidents. Higher rates (i.e., 19% 50%) were usually found following interpersonal 
traumatic events (e.g., assault, rape). 


Development and Course 


By definition, acute stress disorder cannot 
be diagnosed until 
3 days after a traumatic event. 
Although acute stress disorder may progress to posttraumatic stress disorder (PTSD) after 1 
month, it 
may also be a transient 
stress response that 
remits within 1 month of trauma exposure 
and does not 
result 
in PTSD. Approximately half of individuals who eventually develop PTSD 
initially present with acute stress disorder. Longitudinal analyses indicate 


317 


that 
acute stress symptoms can remit, remain constant, or worsen over time, largely as a result 
of 
ongoing life stressors or further traumatic events. 


The forms of reexperiencing can vary across development. Unlike adults or adolescents, 
young children may report 
frightening dreams without 
content 
that 
clearly reflects aspects of the 
trauma (e.g., waking in fright in the aftermath of the trauma but being unable to relate the content 
of the dream 
to the traumatic event). Children age 6 years and younger are more likely than older 
children to express reexperiencing symptoms through play that 
refers directly or symbolically to 



the trauma. For example, a very young child who survived a fire may draw pictures of flames. 
Young children also do not 
necessarily manifest 
fearful 
reactions at 
the time of the exposure or 
even during reexperiencing. Parents typically report 
a range of emotional 
expressions, such as 
anger, shame, or withdrawal, and even excessively bright 
positive affect, in young children who 
are traumatized. Although children may avoid reminders of the trauma, they sometimes become 
preoccupied with reminders (e.g., a young child bitten by a dog may talk about 
dogs constantly 
yet avoid going outside because of fear of coming into contact with a dog). 


Risk and Prognostic Factors 


Temperamental. 
Risk factors include prior mental 
disorder, high levels of negative emotional 
responses such as depressed mood and anxiousness (also termed negative affectivity 
or 
neuroticism), greater perceived severity of the traumatic event, and an avoidant 
coping style. A 
tendency to make catastrophic appraisals of the traumatic experience, often characterized by 
exaggerated appraisals of future harm, guilt, or hopelessness, is strongly predictive of acute 
stress disorder. 


Environmental. 
First 
and foremost, an individual 
must 
be exposed to a traumatic event 
to be at 


risk for acute stress disorder. Risk factors for the disorder include a history of prior trauma. 
Genetic 
and 
physiological. 
Elevated reactivity, as reflected by acoustic startle response, prior to 
trauma exposure increases the risk for developing acute stress disorder. 


Culture-Related Diagnostic Issues 


The profile of symptoms of acute stress disorder may vary cross-culturally, particularly with 
respect 
to dissociative symptoms, nightmares, avoidance, and somatic symptoms (e.g., dizziness, 
shortness of breath, heat 
sensations, pain complaints). Acute stress reactions may be shaped by 
cultural 
values and norms regarding the expression of extreme emotions, even in extraordinary 
situations. Cultural 
concepts of distress shape the local 
symptom 
profiles of acute stress disorder. 
Some cultural 
groups may display variants of dissociative responses, such as possession or 
trancelike behaviors in the initial 
month after trauma exposure. Panic symptoms may be salient 
in acute stress disorder among Cambodians because of the association of traumatic exposure 
with panic-like khy l 
attacks, and ataque de nervios 
among Latin Americans may also follow a 
traumatic exposure. For more information regarding cultural 
concepts of distress, refer to the 
Section III chapter  Culture and Psychiatric Diagnosis.  


Sex- and Gender-Related Diagnostic Issues 


Acute stress disorder is more prevalent 
among women than among men in studies across 
multiple countries. The increased risk for the disorder in women may be attributable to a greater 
likelihood of exposure to the types of traumatic events with a high conditional 
risk for acute 
stress disorder, such as rape, other interpersonal 
violence, and childhood trauma, including 
sexual 
abuse. Other factors likely contributing to the higher prevalence in women include gender 
differences in the emotional and cognitive processing of trauma. Sex-linked 


318 



neurobiological 
differences in stress response as well 
as sociocultural 
factors may also contribute 
to women s increased risk for acute stress disorder. 


Functional 
Consequences of Acute Stress Disorder 


Impaired functioning in social, interpersonal, or occupational 
domains has been shown across 
survivors of accidents, assault, and rape who develop acute stress disorder. The extreme levels of 
anxiety that 
may be associated with acute stress disorder may interfere with sleep, energy levels, 
and capacity to attend to tasks. Avoidance in acute stress disorder can result 
in generalized 
withdrawal 
from 
many situations that 
are perceived as potentially threatening, which can lead to 
nonattendance of medical 
appointments, avoidance of driving to important 
appointments, and 
absenteeism from work. 


Differential 
Diagnosis 


Adjustment 
disorders. 
In adjustment 
disorders, the stressor can be of any severity rather than of 
the severity and type required by Criterion A of acute stress disorder. The diagnosis of an 
adjustment 
disorder is used when the response to a Criterion A event 
does not 
meet 
the criteria 
for acute stress disorder (or another specific mental 
disorder) and when the symptom 
pattern of 
acute stress disorder occurs in response to a stressor that 
does not 
meet 
Criterion A for exposure 
to actual 
or threatened death, serious injury, or sexual 
violence (e.g., spouse leaving, being fired). 
For example, severe stress reactions to life-threatening illnesses that 
may include some acute 
stress disorder symptoms may be more appropriately described as an adjustment 
disorder. Some 
forms of acute stress response do not 
include acute stress disorder symptoms and may be 
characterized by anger, depression, or guilt. These responses are more appropriately described as 
primarily an adjustment 
disorder. Depressive or anger responses in an adjustment 
disorder may 
involve rumination about 
the traumatic event, as opposed to involuntary and intrusive distressing 
memories in acute stress disorder. 


Panic 
disorder. 
Spontaneous panic attacks are very common in acute stress disorder. However, 
panic disorder is diagnosed only if panic attacks are unexpected and there is anxiety about 
future 
attacks or maladaptive changes in behavior associated with fear of dire consequences of the 
attacks. 


Dissociative 
disorders. 
Severe dissociative responses (in the absence of characteristic acute stress 
disorder symptoms) may be diagnosed as derealization/depersonalization disorder. If severe 
amnesia of the trauma persists in the absence of characteristic acute stress disorder symptoms, 
the diagnosis of dissociative amnesia may be indicated. 


Posttraumatic 
stress 
disorder. 
Acute stress disorder is distinguished from 
PTSD because the 
symptom 
pattern in acute stress disorder must 
resolve within 1 month of the traumatic event. If 
the symptoms persist 
for more than 1 month and meet 
criteria for PTSD, the diagnosis is 
changed from acute stress disorder to PTSD. 


Obsessive-compulsive 
disorder. 
In obsessive-compulsive disorder, there are recurrent 
intrusive 
thoughts, but 
these meet 
the definition of an obsession. In addition, the intrusive thoughts are not 
related to an experienced traumatic event, compulsions are usually present, and other symptoms 
of acute stress disorder are typically absent. 


Psychotic 
disorders. 
Flashbacks in acute stress disorder must 
be distinguished from 
illusions, 



hallucinations, and other perceptual 
disturbances that 
may occur in schizophrenia, other 
psychotic disorders, depressive or bipolar disorder with psychotic features, a delirium, 
substance/medication-induced disorders, and psychotic disorders due to another medical 
condition. Acute stress disorder flashbacks are distinguished from 
these other perceptual 
disturbances by being directly related to the traumatic experience and by occurring in the 
absence of other psychotic or substance-induced features. 


319 


Traumatic 
brain 
injury. 
When a brain injury occurs in the context 
of a traumatic event 
(e.g., 
traumatic accident, bomb blast, acceleration/deceleration trauma), symptoms of acute stress 
disorder may appear. An event 
causing head trauma may also constitute a psychological 
traumatic event, and TBI-related neurocognitive symptoms are not 
mutually exclusive and may 
occur concurrently. Symptoms previously termed postconcussive 
(e.g., headaches, dizziness, 
sensitivity to light 
or sound, irritability, concentration deficits) can occur in brain-injured and 
non-brain-injured populations, including individuals with acute stress disorder. Because 
symptoms of acute stress disorder and TBI-related neurocognitive symptoms can overlap, a 
differential 
diagnosis between acute stress disorder and neurocognitive disorder symptoms 
attributable to TBI may be possible based on the presence of symptoms that 
are distinctive to 
each presentation. Whereas reexperiencing and avoidance are characteristic of acute stress 
disorder and not 
the effects of TBI, persistent 
disorientation and confusion are more specific to 
TBI (neurocognitive effects) than to acute stress disorder. Furthermore, differential 
is aided by 
the fact 
that 
symptoms of acute stress disorder persist 
for up to only 1 month following trauma 
exposure. 


Adjustment Disorders 


Diagnostic Criteria 


A. 
The 
development 
of 
emotional or behavioral symptoms in 
response 
to 
an 
identifiable 
stressor(s) occurring 
within 
3 
months of 
the 
onset 
of 
the 
stressor(s). 
B. 
These 
symptoms or behaviors are 
clinically significant, 
as evidenced 
by one 
or 
both 
of 
the 
following: 
1. 
Marked 
distress that 
is out 
of 
proportion 
to 
the 
severity or intensity of 
the 
stressor, 
taking 
into 
account 
the 
external context 
and 
the 
cultural factors that 
might 
influence 
symptom severity and 
presentation. 
2. 
Significant 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
C. 
The 
stress-related 
disturbance 
does not 
meet 
the 
criteria 
for another mental 
disorder and 
is not 
merely an 
exacerbation 
of 
a 
preexisting 
mental disorder. 
D. 
The 
symptoms do 
not 
represent 
normal bereavement 
and 
are 
not 
better 
explained 
by prolonged 
grief 
disorder. 

E. 
Once 
the 
stressor or its consequences have 
terminated, 
the 
symptoms do 
not 
persist 
for more 
than 
an 
additional 6 
months. 
Specify 
whether: 
F43.21 
With 
depressed 
mood: 
Low mood, 
tearfulness, 
or feelings of 
hopelessness are 
predominant. 


F43.22 
With 
anxiety: 
Nervousness, 
worry, 
jitteriness, 
or separation 
anxiety is 


predominant. 
F43.23 
With 
mixed 
anxiety 
and 
depressed 
mood: 
A 
combination 
of 
depression 
and 
anxiety is predominant. 


F43.24 
With 
disturbance 
of conduct: 
Disturbance 
of 
conduct 
is predominant. 
F43.25 
With 
mixed 
disturbance 
of emotions 
and 
conduct: 
Both 
emotional 


symptoms (e.g., 
depression, 
anxiety) and 
a 
disturbance 
of 
conduct 
are 
predominant. 
F43.20 
Unspecified: 
For maladaptive 
reactions that 
are 
not 
classifiable 
as one 


of 
the 
specific subtypes of 
adjustment 
disorder. 


320 


Specify 
if: 


Acute: 
This specifier can 
be 
used 
to 
indicate 
persistence 
of 
symptoms for less 
than 
6 
months. 
Persistent (chronic): 
This specifier can 
be 
used 
to 
indicate 
persistence 
of 


symptoms for 6 
months or longer. 
By definition, 
symptoms cannot 
persist 
for 
more 
than 
6 
months after the 
termination 
of 
the 
stressor or its consequences. 
The 
persistent 
specifier therefore 
applies when 
the 
duration 
of 
the 
disturbance 
is 
longer than 
6 
months in 
response 
to 
a 
chronic stressor or to 
a 
stressor that 
has 
enduring 
consequences. 


Specifiers 


By definition, an adjustment 
disorder must 
resolve within 6 months of the termination of the 
stressor or its consequences. However, the symptoms may persist 
for a prolonged period (i.e., 
longer than 6 months) if they occur in response to a persistent 
stressor (e.g., a chronic disabling 
other medical 
condition) or to a stressor that 
has enduring consequences (e.g., the financial 
and 
emotional 
difficulties resulting from 
a divorce). The duration of the symptoms of an adjustment 
disorder can be indicated by using the acute or persistent 
(chronic) specifiers. The acute specifier 
is used to indicate persistence of symptoms for less than 6 months. The persistent 
(chronic) 
specifier is used to indicate persistence of symptoms for 6 months or longer. This latter specifier 
therefore applies when the duration of the disturbance is longer than 6 months in response to a 
persistent stressor or to a stressor that has enduring consequences. 


Diagnostic Features 



The presence of emotional 
or behavioral 
symptoms in response to an identifiable stressor is the 
essential 
feature of adjustment 
disorders (Criterion A). The stressor may be a single event 
(e.g., a 
termination of a romantic relationship), or there may be multiple stressors (e.g., marked business 
difficulties and marital 
problems). Stressors may be recurrent 
(e.g., associated with seasonal 
business crises, unfulfilling sexual 
relationships) or continuous (e.g., a persistent 
painful 
illness 
with increasing disability, living in a crime-ridden neighborhood). Stressors may affect 
a single 
individual, an entire family, or a larger group or community (e.g., a natural 
disaster). Some 
stressors may accompany specific developmental 
events (e.g., going to school, leaving a parental 
home, reentering a parental 
home, getting married, becoming a parent, failing to attain 
occupational goals, retirement). 


Adjustment 
disorders may be diagnosed following the death of a loved one when the 
intensity, quality, or persistence of grief reactions exceeds what 
normally might 
be expected, 
when cultural, religious, or age-appropriate norms are taken into account 
and the grief reaction 
does not meet criteria for prolonged grief disorder. 


Prevalence 


Adjustment 
disorders are common, although prevalence may vary widely as a function of the 
population studied and the assessment 
methods used. The percentage of individuals in outpatient 
mental 
health treatment 
in the United States with a principal 
diagnosis of an adjustment 
disorder 
ranges from 
approximately 5% to 20%. Rates of adjustment 
disorder may be higher in women, 
as noted by research in Denmark. In Australian, Canadian, Israeli, and U.S. hospital 
psychiatric 
consultation settings, an adjustment 
disorder was often the most 
common diagnosis in the 1990s, 
frequently reaching 50%. 


Development and Course 


By definition, the disturbance in adjustment 
disorders begins within 3 months of onset 
of a 
stressor. If the stressor is an acute event 
(e.g., being fired from 
a job), the onset 
of the 
disturbance is usually immediate (i.e., within a few days) and the duration is relatively brief 


321 


(i.e., no more than a few months). If the stressor or its consequences persist, the adjustment 
disorder may also continue to be present 
and become the persistent 
form. By definition, if 
symptoms persist 
beyond 6 months after the stressor or its consequences have ceased, the 
diagnosis of adjustment disorder would no longer apply. 


Risk and Prognostic Factors 


Environmental. 
Persons from 
disadvantaged life circumstances experience a high rate of stressors 
and may be at increased risk for adjustment disorders. 


Culture-Related Diagnostic Issues 


Because the nature, meaning, and experience of the stressors and the evaluation of the response 
to stressors may vary across cultures, cultural 
context 
is key in determining whether the 



adjustment 
response is maladaptive. Migrants and refugees may experience stressful 
major 
contextual 
and cultural 
changes that 
can make this assessment 
challenging. Suffering is assumed 
to be an intrinsic aspect 
of normal 
life in some cultural 
contexts, such that 
distressful 
reactions to 
stressful life events may not be viewed as maladaptive or worthy of treatment. Self-immolation is 
also a risk associated with adjustment disorder in some cultural contexts. 


Association With Suicidal 
Thoughts or Behavior 


Adjustment 
disorders are associated with an increased risk of suicide attempts and suicide. 
Among migrant 
populations, including Turkish migrants in Western Europe and South Asian or 
South East 
Asian migrants in Gulf countries, adjustment 
disorder was found to be among the 
most common diagnoses associated with suicide-related behavior. 


Functional 
Consequences of Adjustment Disorders 


The subjective distress or impairment 
in functioning associated with adjustment 
disorders is 
frequently manifested as decreased performance at 
work or school 
and temporary changes in 
social 
relationships. An adjustment 
disorder may complicate the course of illness in individuals 
who have another medical 
condition (e.g., decreased compliance with the recommended medical 
regimen; increased length of hospital stay). 


Differential 
Diagnosis 


Major depressive 
disorder. 
If an individual 
has symptoms that 
meet 
criteria for a major depressive 
disorder in response to a stressor, the diagnosis of an adjustment 
disorder is not 
applicable. The 
symptom profile of major depressive disorder differentiates it from adjustment disorders. 
Posttraumatic 
stress 
disorder and 
acute 
stress 
disorder. 
In adjustment 
disorders, the stressor can be 


of any severity rather than of the severity and type required by Criterion A of acute stress 
disorder and posttraumatic stress disorder (PTSD). In distinguishing adjustment 
disorders from 
these two posttraumatic diagnoses, there are both timing and symptom 
profile considerations. 
Adjustment 
disorders can be diagnosed immediately and persist 
up to 6 months after exposure to 
the traumatic event, whereas acute stress disorder can only occur between 3 days and 1 month of 
exposure to the stressor, and PTSD cannot 
be diagnosed until 
at 
least 
1 month has passed since 
the occurrence of the traumatic stressor. The required symptom 
profiles for PTSD and acute 
stress disorder differentiate them 
from 
the adjustment 
disorders. With regard to symptom 
profiles, an adjustment 
disorder may be diagnosed following a traumatic event 
when an 
individual 
exhibits symptoms of either acute stress disorder or PTSD that 
do not 
meet 
or exceed 
the diagnostic threshold for either disorder. Because adjustment 
disorder cannot 
persist 
for more 
than 6 months after termination of the stressor or its consequences, cases in which symptoms 
occurring in response 


322 


to a traumatic event 
that 
fall 
short 
of the diagnostic threshold for PTSD and that 
persist 
for 
longer than 6 months should be diagnosed as other specified trauma- and stressor-related 
disorder. An adjustment 
disorder should also be diagnosed for individuals who have not 
been 
exposed to a traumatic event 
meeting Criterion A for PTSD, but 
who otherwise exhibit 
the full 



symptom profile of either acute stress disorder or PTSD. 
Personality 
disorders. 
With regard to personality disorders, some personality features may be 
associated with a vulnerability to situational 
distress that 
may resemble an adjustment 
disorder. 
The lifetime history of personality functioning will 
help inform 
the interpretation of distressed 
behaviors to aid in distinguishing a long-standing personality disorder from 
an adjustment 
disorder. In addition to some personality disorders incurring vulnerability to distress, stressors 
may also exacerbate personality disorder symptoms. In the presence of a personality disorder, if 
the symptom 
criteria for an adjustment 
disorder are met, and the stress-related disturbance 


exceeds what 
may be attributable to maladaptive personality disorder symptoms (i.e., Criterion C 
is met), then the diagnosis of an adjustment disorder should be made. 
Bereavement. 
Clinically significant 
acute bereavement-related distress may sometimes be 


diagnosed as an adjustment 
disorder if the bereavement 
is judged to be out 
of proportion to what 
would be expected or significantly impairs self-care and interpersonal 
relations. When such 
symptoms persist 
for more than 12 months after the death, the diagnosis is either prolonged grief 
disorder if full criteria are met or else other specified trauma- and stressor-related disorder. 
Psychological 
factors 
affecting 
other medical 
conditions. 
In psychological 
factors affecting other 


medical 
conditions, specific psychological 
entities (e.g., psychological 
symptoms, behaviors, 
other factors) exacerbate a medical 
condition. These psychological 
factors can precipitate, 
exacerbate, or put 
an individual 
at 
risk for medical 
illness, or they can worsen an existing 
condition. In contrast, an adjustment 
disorder is a reaction to the stressor (e.g., having a medical 
illness). 


Normative 
stress 
reactions. 
When bad things happen, most 
people get 
upset. This is not 
an 
adjustment disorder. The diagnosis should only be made when the magnitude of the distress (e.g., 
alterations in mood, anxiety, or conduct) exceeds what 
would normally be expected (which may 
vary in different cultures) or when the adverse event precipitates functional impairment. 


Comorbidity 


Adjustment 
disorders can accompany most 
mental 
disorders and any medical 
condition. 
Adjustment 
disorders can be diagnosed in addition to another mental 
disorder only if the latter 
does not 
explain the particular symptoms that 
occur in reaction to the stressor. For example, an 
individual 
may develop an adjustment 
disorder, with depressed mood, after losing a job and at 
the same time have a diagnosis of obsessive-compulsive disorder. Or, an individual 
may have a 
depressive or bipolar disorder and an adjustment 
disorder as long as the criteria for both are met. 
Adjustment 
disorders are common accompaniments of medical 
illness and may be the major 
psychological response to a medical condition. 


Prolonged 
Grief Disorder 


Diagnostic Criteria 
F43.8 
A. 
The 
death, 
at 
least 
12 
months ago, 
of 
a 
person 
who 
was close 
to 
the 
bereaved 



individual (for children 
and 
adolescents, 
at 
least 
6 
months ago). 


323 


B. 
Since 
the 
death, 
the 
development 
of 
a 
persistent 
grief 
response 
characterized 
by 
one 
or both 
of 
the 
following 
symptoms, 
which 
have 
been 
present 
most 
days to 
a 
clinically significant 
degree. 
In 
addition, 
the 
symptom(s) has occurred 
nearly 
every day for at 
least 
the 
last 
month: 
1. 
Intense 
yearning/longing 
for the 
deceased 
person. 
2. 
Preoccupation 
with 
thoughts or memories of 
the 
deceased 
person 
(in 
children 
and 
adolescents, 
preoccupation 
may focus on 
the 
circumstances of 
the 
death). 
C. 
Since 
the 
death, 
at 
least 
three 
of 
the 
following 
symptoms have 
been 
present 
most 
days to 
a 
clinically significant 
degree. 
In 
addition, 
the 
symptoms have 
occurred 
nearly every day for at 
least 
the 
last 
month: 
1. 
Identity disruption 
(e.g., 
feeling 
as though 
part 
of 
oneself 
has died) since 
the 
death. 
2. 
Marked 
sense 
of 
disbelief 
about 
the 
death. 
3. 
Avoidance 
of 
reminders that 
the 
person 
is dead 
(in 
children 
and 
adolescents, 
may be 
characterized 
by efforts to 
avoid 
reminders). 
4. 
Intense 
emotional pain 
(e.g., 
anger, 
bitterness, 
sorrow) related 
to 
the 
death. 
5. 
Difficulty reintegrating 
into 
one s relationships and 
activities after the 
death 
(e.g., 
problems engaging 
with 
friends, 
pursuing 
interests, 
or planning 
for the 
future). 
6. 
Emotional numbness (absence 
or marked 
reduction 
of 
emotional experience) 
as a 
result 
of 
the 
death. 
7. 
Feeling 
that 
life 
is meaningless as a 
result 
of 
the 
death. 
8. 
Intense 
loneliness as a 
result 
of 
the 
death. 
D. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
E. 
The 
duration 
and 
severity of 
the 
bereavement 
reaction 
clearly exceed 
expected 
social, 
cultural, 
or religious norms for the 
individual s culture 
and 
context. 
F. 
The 
symptoms are 
not 
better explained 
by another mental disorder, 
such 
as 
major depressive 
disorder or posttraumatic stress disorder, 
and 
are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
medication, 
alcohol) 
or another medical condition. 
Diagnostic Features 


Prolonged grief disorder represents a prolonged maladaptive grief reaction that 
can be diagnosed 
only after at 
least 
12 months (6 months in children and adolescents) have elapsed since the death 
of someone with whom 
the bereaved had a close relationship (Criterion A). Although in general 



this time frame reliably discriminates normal 
grief from 
grief that 
continues to be severe and 
impairing, the duration of adaptive grief may vary individually and cross-culturally. The 
condition involves the development 
of a persistent 
grief response characterized by intense 
yearning or longing for the deceased person (often with intense sorrow and frequent 
crying) or 
preoccupation with thoughts or memories of the deceased, although in children and adolescents, 
this preoccupation may focus on the circumstances of the death. The intense yearning/longing or 
the preoccupation has been present 
most 
days to a clinically significant 
degree and has occurred 
nearly every day for at 
least 
the last 
month (Criterion B). Moreover, since the death, at 
least 
three 
additional 
symptoms have been present 
most 
days to a clinically significant 
degree and have 
occurred nearly every day for at 
least 
the past 
month. These symptoms include identity 
disruption since the death (e.g., feeling as though part 
of oneself has died) (Criterion C1); 
a 
marked sense of disbelief about 
the death (Criterion C2); 
avoidance of reminders that 
the person 
is dead, which in children and adolescents may be characterized by efforts to avoid reminders 
(Criterion C3); 
intense emotional 
pain (e.g., anger, bitterness, guilt) since the death (Criterion 
C4); 
having difficulty reintegrating into personal 
relationships and activities since the death (e.g., 
problems 


324 


engaging with friends, pursuing interests, or planning for the future) (Criterion C5); 
emotional 
numbness (absence or marked reduction of emotional 
experience) as a result 
of the death 
(Criterion C6); 
feeling that 
life is meaningless as a result 
of the death (Criterion C7); 
or intense 
loneliness as a consequence of the death (Criterion C8). 


The symptoms of prolonged grief disorder must 
result 
in clinically significant 
distress or 
impairment 
in social, occupational, or other important 
areas of functioning in the bereaved 
individual 
(Criterion D). The nature, duration, and severity of the bereavement 
reaction must 
clearly exceed expected social, cultural, or religious norms for the individual s culture and 
context 
(Criterion E). Although there are variations in how grief can manifest, the symptoms of 
prolonged grief disorder occur across genders and in diverse social and cultural groups. 


Associated Features 


Individuals with symptoms of prolonged grief disorder often experience maladaptive cognitions 
about 
the self, guilt 
about 
the death, and diminished future life expectancy and life goals. 
Somatic complaints commonly accompany the condition and may be related to comorbid 
depression and anxiety, social 
identity disruption, and increased health care visits; 
the somatic 
symptoms may be associated with those that 
were experienced by the deceased (e.g., changes in 
appetite). Harmful 
health behaviors related to decreased self-care and concern are also common 
in individuals with symptoms of prolonged grief disorder. Hallucinations about 
the deceased 
(e.g., hearing the deceased person s voice) may occur during normal 
grief but 
may be more 
common in individuals with symptoms of prolonged grief disorder; 
hallucinations experienced 
by individuals with prolonged grief disorder symptoms may be associated with disruptions of 
social 
identity and purpose related to the death (e.g., confusion about 
one s role in life, feeling of 
meaninglessness). Other associated features of prolonged grief disorder include bitterness, anger, 
or restlessness; blaming others for the death; and decreased sleep quantity and quality. 



Prevalence 


The prevalence of DSM-5 prolonged grief disorder in adults is unknown. Meta-analysis of 
studies across four continents that 
used a different 
definition for prolonged grief disorder with at 
least 
a 6-month duration postloss suggests a pooled prevalence of 9.8%; 
however, there was 
substantial 
methodological 
heterogeneity across studies (e.g., in symptom 
definitions, measures, 
duration of bereavement), which affected the prevalence findings. Populations with elevated 
exposure to trauma may have higher prevalence rates. Mean prevalence of prolonged grief 
presentations may be higher in high-income Western countries than in high- and upper-middleincome 
Asian countries, but 
recent 
studies in China have revealed higher rates and substantial 
variation. Prevalence of persistent 
complex bereavement 
disorder (included in DSM-5 Section 
III,  Conditions for Further Study ) among bereaved U.S. youth in the community was estimated 
at 18%. 


Development and Course 


There are limited data on the course of prolonged grief disorder across the life span. Symptoms 
usually begin within the initial 
months after the death, although there may be a delay before the 
full 
syndrome appears. Preliminary evidence suggests that 
course may be especially prolonged 
among parents after the death of a child. The course of prolonged grief disorder may be 
complicated by comorbid posttraumatic stress disorder, which is more common in situations of 
bereavement 
following the violent 
death of a loved one (e.g., murder, suicide) when grief for the 
bereaved may be accompanied by personal 
life threat 
and/or witnessing of violent 
and potentially 
gruesome death. Older age may be associated with a higher risk of developing the disorder after 
the death of a loved one. Older adults with prolonged grief disorder symptoms may be at 
elevated risk for progressive cognitive decline. 


325 


In children, distress may be expressed in play and behavior, developmental 
regressions, and 
anxious or protest 
behavior at 
times of separation and reunion. Young children may experience 
symptoms of prolonged grief disorder in specific ways because of their age. The loss of a 
primary caregiver may be particularly traumatic for a young child, given the disorganizing 
effects of the caregiver s absence. Young children may protest 
or become angry when daily care 
activities are performed differently than by the deceased (e.g., cooking, discipline, bedtime 
rituals). They may express intense insecurity about 
their future, often manifested as worries 
about 
the health and safety of caregivers and about 
themselves, with repeated questions about 
death. They may engage in searching for the deceased because they do not 
understand the 
permanence of death. Young children tend toward somatic manifestations such as disturbances in 
sleep, eating, digestion, and level 
of energy. They may express yearning in thought 
and play as a 
wish, literally, to physically reunite with the deceased to overcome the painful 
physical 
separation (e.g., to climb a ladder to heaven or lie in the ground next 
to a parent). Young children 
typically do not 
understand or describe numbing, whereas adolescents may describe  not 
feeling 
anything.  


In children and adolescents, ongoing preoccupation with the circumstances of the death 
might 
involve focusing on distressing aspects of physical 
deterioration over the course of a fatal 



illness and/or the inability of a caregiver to perform 
vital 
caregiving functions. Identity 
disruption may include feeling profoundly different 
from 
others, often in response to loss 
reminders (e.g., making Mother s Day cards at 
school, watching a friend enjoy a hobby with a 
sibling). Children and adolescents may verbally, in their behavior, or through emotional 
withdrawal 
show reluctance to join adults in activities that 
serve as loss reminders. They may 
experience intense emotional 
pain over feeling deprived ( robbed ) of the deceased s help with 
ongoing developmental 
tasks (e.g., onset 
of menses). Separation distress may be predominant 
in 
younger children, and distress over disruptions in social 
identity (e.g., confusion about 
purpose 
in life) and risk for comorbid depression can increasingly manifest 
in older children and 
adolescents. 


Failure to achieve age-appropriate developmental 
milestones and transitions is a 
manifestation of failure to reintegrate into life roles. For older children and adolescents, feeling 
that 
life is meaningless without 
the person who died may include giving up on developmental 
aspirations ( It s not 
worth trying if they can t 
be here ), not 
caring about 
risky behavior ( So 
what 
if I get 
hurt 
or die? ), or feeling that 
their future is  ruined.  Older children and adolescents 
may be apprehensive over sharing a similar fate as the deceased, including premature death. 
Loneliness may be intensified by keeping grief private, sometimes over not 
wanting to add to the 
distress of a grieving caregiver or to avoid presumed stigma from peers. 


Risk and Prognostic Factors 


Environmental. 
Risk for prolonged grief disorder symptoms is heightened by increased 
dependency on the deceased prior to the death, by the death of a child, by violent 
or unexpected 
deaths, and by economic stressors. The disorder has a higher prevalence following the death of a 
spouse/partner or child compared with other kinship relationships to the deceased. Disturbances 
in caregiver availability and support increase the risk for bereaved children. 


Culture-Related Diagnostic Issues 


The symptoms of prolonged grief disorder are observed across cultural 
settings, but 
grief 
responses may manifest 
in culturally specific ways, including in expected duration, and show 
historical 
variation. For example, across cultures, nightmares about 
the deceased may be 
especially distressing because of their attributed significance; 
the prevalence of hallucinations of 
the deceased or of grief-related somatic symptoms may vary; 
and indirect 
expressions of 
prolonged grief disorder related functional impairment (e.g., unhealthy 


326 


behaviors like drinking or poor self-care) may be more prevalent 
than direct 
expressions of grief. 
The inability to carry out 
funerary rituals in some cultures may worsen symptoms of prolonged 
grief disorder, possibly because of interpretation of their impact 
on the spiritual 
status of the 
deceased. Some studies suggest 
higher prevalence of the symptoms of prolonged grief disorder 
in African Americans relative to non-Hispanic Whites; 
the cause for these elevations requires 
further study in areas such as differential 
exposure to sudden or violent 
death. Differences in 
mourning practices may contribute to the cultural 
prescription or prohibition of specific grief 
expressions, and cultural 
norms about 
the social 
status of the bereaved may affect 
grief intensity 



and duration, such as different 
levels of support 
or societal 
sanction toward remarriage 
depending on the gender of the bereaved. Diagnosis of the disorder requires that 
the persistent 
and severe responses go beyond cultural 
norms of grief responses and not 
be better explained by 
culturally specific mourning rituals. 


Sex- and Gender-Related Diagnostic Issues 


Some studies find higher disorder prevalence or symptom 
severity among bereaved women, but 
other studies conclude the gender disparity is small and/or not statistically significant. 


Association With Suicidal 
Thoughts or Behavior 


Individuals with symptoms of prolonged grief disorder are at 
heightened risk for suicidal 
ideation, even after adjustment 
for the effect 
of major depression and PTSD. The association of 
prolonged grief disorder symptoms and suicidal 
ideation is consistent 
across the life span and 
cross-nationally. However, the existing literature does not 
establish whether suicidal 
ideation 
associated with symptoms of prolonged grief disorder is linked to a higher incidence of suicidal 
behavior. Stigma, isolation, thwarted belongingness, avoidance, and psychological 
distress in 
bereaved individuals are associated with suicidal 
ideation. Compared with individuals whose 
bereavement 
is due to nonviolent 
causes, individuals whose prolonged grief disorder symptoms 
are the result 
of a violent 
loss (e.g., homicide, suicide, accident) are at 
greater risk for suicidal 
ideation. Similarly, individuals who experience the death of a child, especially if the child is 
younger than 25, are more likely to develop prolonged grief disorder symptoms that 
are 
associated with suicidal ideation. 


Functional 
Consequences of Prolonged Grief Disorder 


Symptoms of prolonged grief disorder are associated with impairments in work and social 
functioning and with harmful 
health behaviors, such as increased tobacco and alcohol 
use. They 
are also associated with marked increases in risks for serious medical 
conditions, including 
cardiac disease, hypertension, cancer, immunological 
deficiency, and reduced quality of life. 
Long-term 
developmental 
consequences among children and adolescents include premature 
school 
withdrawal, diminished educational 
aspirations, and reduced academic attainment; 
young 
women in particular may be hesitant 
to marry as they transition to adulthood. Impaired cognitive 
functioning may be associated with symptoms of prolonged grief disorder, especially in middle-
age and older adults. 


Differential 
Diagnosis 


Normal 
grief. 
Prolonged grief disorder is distinguished from 
normal 
grief by the presence of 
severe grief reactions that 
persist 
at 
least 
12 months (6 months in children or adolescents) after 
the death of a person who was close to the bereaved individual. It 
is only when severe levels of 
grief response persist 
for the specified duration following the death, interfere with the 
individual s capacity to function, and exceed cultural, social, or religious norms that 
prolonged 
grief disorder is diagnosed. In evaluating the requirement 
for clinically significant 
symptoms to 
be present 
most 
days over the past 
month, it 
should be noted that 
marked increases in grief 
severity can be seen in normal grieving around calendar 



327 


days that 
are reminders of the loss, such as the anniversary of the death, birthdays, wedding 
anniversaries, and holidays; 
this exacerbation of grief severity does not 
by itself, in the absence 
of persistent grief at other times, constitute evidence of prolonged grief disorder. 


Depressive 
disorders. 
Prolonged grief disorder, major depressive disorder, and persistent 
depressive disorder share several 
symptoms, including low mood, crying, and suicidal 
thinking. 
However, in prolonged grief disorder the distress is focused on feelings of loss and separation 
from 
a loved one rather than reflecting generalized low mood. Major depressive disorder may 
also be preceded by the death of a loved one, with or without comorbid prolonged grief disorder. 


Posttraumatic 
stress 
disorder. 
Individuals who experience bereavement 
as a result 
of violent 
or 
accidental 
death may develop both PTSD and prolonged grief disorder. Both conditions can 
involve intrusive thoughts and avoidance. Whereas intrusions in PTSD revolve around the 
traumatic event 
(which may have caused the death of a loved one), intrusive memories in 
prolonged grief disorder focus on thoughts about 
many aspects of the relationship with the 
deceased, including positive aspects of the relationship and distress over the separation. Unlike 
avoidance in PTSD, which is manifested by avoidance of memories, thoughts, or feelings 
associated with the traumatic event 
that 
led to the death of the loved one (e.g., memories of the 
fatal 
automobile accident 
that 
killed the loved one), the avoidance in prolonged grief disorder is 
of reminders that 
the loved one is no longer present 
(e.g., avoidance of activities carried out 
together with the deceased). Moreover, reexperiencing memories in PTSD tend to be more 
perceptual, with the individual 
reporting that 
the memory feels like it 
is occurring in the  here 
and now,  which tends not 
to be the case in prolonged grief disorder. In prolonged grief disorder, 
there is also a yearning for the deceased, which is absent in PTSD. 


Separation 
anxiety 
disorder. 
Separation anxiety disorder is characterized by anxiety about 
separation from 
current 
attachment 
figures, whereas prolonged grief disorder involves distress 
about separation from a deceased person. 


Psychotic 
disorder. 
Hallucinations about 
the deceased (e.g., seeing the deceased in a favorite 
chair) or transient 
sensations about 
the presence of the deceased (e.g., by touch, voice, or sight) 
are common cross-culturally during normal 
grief, may be experienced as reassuring, and often 
occur while the individual 
is falling asleep (hypnagogic). To receive a diagnosis of psychotic 
disorder, individuals with prolonged grief disorder must 
also endorse other symptoms of 
psychosis, such as delusions, disorganized thinking, or negative symptoms. 


Comorbidity 


The most 
common comorbid disorders with symptoms of prolonged grief disorder are major 
depressive disorder, PTSD, and substance use disorders. PTSD is more frequently comorbid with 
prolonged grief disorder symptoms when the death occurred in violent 
or accidental 
circumstances. Separation anxiety disorder involving major living attachment 
figures may be 
comorbid with symptoms of prolonged grief disorder. 


Other Specified 
Trauma- and 
Stressor-Related 
Disorder 



F43.8 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
trauma-
and 
stressor-related 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 


328 


full criteria 
for any of 
the 
disorders in 
the 
trauma- and 
stressor-related 
disorders 
diagnostic class. 
The 
other specified 
trauma- and 
stressor-related 
disorder category 
is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific 
reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific trauma- and 
stressor-related 
disorder. 
This is done 
by recording 
 other specified 
trauma- and 
stressor-related 
disorder  followed 
by the 
specific reason 
(e.g., 
 persistent 
response 
to 
trauma 
with 
PTSD-like 
symptoms ). 


Examples of 
presentations that 
can 
be 
specified 
using 
the 
 other specified  
designation 
include 
the 
following: 


1. 
Adjustment-like 
disorders 
with 
delayed 
onset of symptoms 
that occur more 
than 
3 
months 
after the 
stressor. 
2. 
Adjustment-like 
disorders 
with 
prolonged 
duration 
of more 
than 
6 
months 
without prolonged 
duration 
of stressor. 
3. 
Persistent response 
to 
trauma 
with 
PTSD-like 
symptoms 
(i.e., 
symptoms 
occurring 
in 
response 
to 
a 
traumatic event 
that 
fall short 
of 
the 
diagnostic 
threshold 
for PTSD and 
that 
persist 
for longer than 
6 
months, 
sometimes referred 
to 
as  subthreshold/partial PTSD ). 
4. 
Ataque 
de 
nervios: 
See 
 Culture 
and 
Psychiatric Diagnosis  in 
Section 
III. 
5. 
Other cultural 
syndromes: 
See 
 Culture 
and 
Psychiatric Diagnosis  in 
Section 
III. 
Unspecified 
Trauma- and 
Stressor-Related 
Disorder 


F43.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
trauma-
and 
stressor-related 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
trauma- and 
stressor-related 
disorders diagnostic class. 
The 
unspecified 
trauma- and 
stressor-related 
disorder 
category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific trauma- and 
stressor-related 
disorder and 
includes presentations in 
which 
there 
is insufficient 
information 
to 
make 
a 
more 



specific diagnosis (e.g., 
in 
emergency room settings). 



329 



Dissociative Disorders 


Dissociative disorders 
are characterized by a disruption of and/or discontinuity in the 
normal 
integration of consciousness, memory, identity, emotion, perception, body representation, 
motor control, and behavior. Dissociative symptoms can potentially disrupt 
every area of 
psychological 
functioning. This chapter includes dissociative identity disorder, dissociative 
amnesia, depersonalization/derealization disorder, other specified dissociative disorder, and 
unspecified dissociative disorder. 


Dissociative disorders are frequently found in the aftermath of a wide variety of 
psychologically traumatic experiences in children, adolescents, and adults. Throughout 
this 
chapter,  traumatic experiences  refers to experiences that 
result 
in psychological 
sequelae, as 
opposed to the physical 
impact 
that 
can cause traumatic brain injury. Therefore, in DSM-5, the 
dissociative disorders are placed next 
to, but 
are not 
part 
of, the trauma- and stressor-related 
disorders, reflecting the close relationship between these diagnostic classes. Both acute stress 
disorder and posttraumatic stress disorder include dissociative symptoms, such as amnesia, 
flashbacks, numbing, and depersonalization/derealization. 


Dissociative symptoms are experienced as unbidden intrusions into awareness and behavior, 
with accompanying losses of continuity in subjective experience (i.e.,   positive   dissociative 
symptoms such as division of identity, depersonalization, and derealization) and/or inability to 
access information or to control 
mental 
functions that 
normally are readily amenable to access or 
control (i.e.,  negative  dissociative symptoms such as amnesia). 


Across cultural 
contexts, risk factors for dissociative pathology include earlier onset 
of 
trauma; 
neglect 
and sexual, physical, and emotional 
abuse by parents; 
cumulative early life 
trauma and adversities; 
and repeated sustained trauma or torture associated with captivity (e.g., 
experienced by prisoners of war, victims of trafficking). 


Depersonalization/derealization disorder 
is characterized by clinically significant 
persistent 
or recurrent 
depersonalization (i.e., experiences of unreality or detachment 
from 
one s mind, self, 
or body) and/or derealization (i.e., experiences of unreality or detachment 
from 
one s 
surroundings). These alterations of experience are accompanied by intact 
reality testing. There is 
no evidence of any distinction between predominantly depersonalization and predominantly 
derealization symptoms. Individuals with this disorder can have depersonalization, derealization, 
or both. 


Dissociative amnesia 
is characterized by an inability to recall 
autobiographical 
information 
that 
is inconsistent 
with normal 
forgetting. The amnesia may be localized (i.e., an event 
or period 
of time), selective (i.e., a specific aspect 
of an event), or generalized (i.e., identity and life 
history). In dissociative amnesia, memory deficits are primarily retrograde and often associated 
with traumatic experiences (e.g., lack of recall 
of third grade when the individual 
was kidnapped 
and held hostage). Although some individuals with amnesia promptly notice that 
they have gaps 
or a sense of fragmentation in their remote memory, most 
individuals with dissociative disorders 



are initially unaware of their amnesia or minimize or rationalize the deficits. For them, awareness 
of amnesia occurs when they realize that 
they do not 
recall 
their personal 
identity or when 
circumstances make these individuals aware that 
important 
autobiographical 
information is 
missing (e.g., when they discover 


330 


evidence or are told of past 
events that 
they cannot 
recall). Generalized dissociative amnesia 
with loss of a major part or all of the individual s life history and/or identity is rare. 


Dissociative identity disorder 
is characterized by a) the presence of two or more distinct 
personality states or an experience of possession and b) recurrent 
episodes of dissociative 
amnesia. The fragmentation/division of identity may vary across cultural 
contexts (e.g., 
possession-form 
presentations) and with circumstance. Thus, individuals may experience 
discontinuities in identity and memory that 
may not 
be immediately evident 
to others or are 
obscured by attempts to hide dysfunction. Individuals with dissociative identity disorder 
experience recurrent, inexplicable intrusions into their conscious functioning and sense of self 
(e.g., voices; 
dissociated actions and speech; 
intrusive thoughts, emotions, and impulses); 
alterations of sense of self (e.g., attitudes, preferences, and feeling like their body or actions are 
not 
their own); 
odd changes of perception (e.g., depersonalization or derealization, such as 
feeling detached, as if watching themself from 
outside their body); 
and intermittent 
functional 
neurological 
symptoms. Stress often produces transient 
exacerbation of dissociative symptoms 
that makes them more evident. 


The residual 
category of other specified dissociative disorder 
includes presentations in which 
symptoms characteristic of a dissociative disorder that 
cause clinically significant 
distress or 
impairment 
predominate but 
do not 
meet 
the criteria for any of the specific dissociative 
disorders. Examples include identity disturbances associated with less-than-marked 
discontinuities in sense of self and agency, alterations of identity, or episodes of possession in 
the absence of a history of episodes of dissociative amnesia; 
identity disturbance due to 
prolonged and intensive coercive persuasion as may occur in sects/cults or terrorist 
organizations; 
acute dissociative reactions to stressful 
events that 
last 
less than 1 month; 
and 
dissociative trance, which is characterized by an acute narrowing or complete loss of awareness 
of immediate surroundings that 
manifests as profound unresponsiveness or insensitivity to 
environmental stimuli. 


Dissociative Identity Disorder 


Diagnostic Criteria 
F44.81 


A. 
Disruption 
of 
identity characterized 
by two 
or more 
distinct 
personality states, 
which 
may be 
described 
in 
some 
cultures as an 
experience 
of 
possession. 
The 
disruption 
in 
identity involves marked 
discontinuity in 
sense 
of 
self 
and 
sense 
of 
agency, 
accompanied 
by related 
alterations in 
affect, 
behavior, 
consciousness, 
memory, 
perception, 
cognition, 
and/or sensory-motor functioning. 
These 
signs 

and 
symptoms may be 
observed 
by others or reported 
by the 
individual. 


B. 
Recurrent 
gaps in 
the 
recall of 
everyday events, 
important 
personal information, 
and/or traumatic events that 
are 
inconsistent 
with 
ordinary forgetting. 
C. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
D. 
The 
disturbance 
is not 
a 
normal part 
of 
a 
broadly accepted 
cultural or religious 
practice. 
Note: 
In 
children, 
the 
symptoms are 
not 
better explained 
by imaginary playmates 
or other fantasy play. 


E. 
The 
symptoms are 
not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
blackouts or chaotic behavior during 
alcohol intoxication) or another 
medical condition 
(e.g., 
complex partial seizures). 
331 


Diagnostic Features 


The defining feature of dissociative identity disorder is the presence of two or more distinct 
personality states or an experience of possession (Criterion A). The overtness or covertness of 
these personality states varies as a function of psychological 
motivation, current 
level 
of stress, 
cultural 
context, internal 
conflicts and dynamics, and emotional 
resilience, among other factors. 
Sustained periods of identity confusion/alteration may occur when psychosocial 
pressures are 
severe and/or prolonged. In those cases of dissociative identity disorder that 
present 
as the 
individual 
being possessed by external 
identities (e.g., spirits, demons) (possession-form 
dissociative identity disorder), and in a small 
proportion of non-possession-form 
cases, 
manifestations of alternate identities are readily observable. Most 
individuals with nonpossession-
form 
dissociative identity disorder do not 
overtly display, or only subtly display, their 
discontinuity of identity, and only a minority present 
to clinical 
attention with discernible 
alternation of identities. The elaboration of dissociative personality states with different 
names, 
wardrobes, hairstyles, handwritings, accents, and so forth, occurs in only a minority 
of 
individuals with the non-possession-form 
dissociative identity disorder and is not 
essential 
to 
diagnosis. In those cases where alternate personality states cannot 
be directly observed, the 
presence of distinct 
personality states can be identified by sudden alterations or discontinuities in 
the individual s sense of self and sense of agency (Criterion A), and recurrent 
dissociative 
amnesias (Criterion B). 


Criterion A symptoms are related to discontinuities of experience that 
can affect 
any aspect 
of an individual s functioning. Individuals with dissociative identity disorder may report 
the 
feeling that 
they have suddenly become depersonalized observers of their own speech and 
actions, which they may feel 
powerless to stop (i.e., impaired sense of self and impaired sense of 
agency). These individuals may also report 
perceptions of voices (e.g., a child s voice, voices 
commenting on the individual s thoughts or behavior, persecutory voices and command 
hallucinations). In some cases, hearing voices is specifically denied, but 
the individual 
reports 
multiple, perplexing, independent 
thought 
streams over which the individual 
experiences no 
control. Individuals with dissociative identity disorder may report 
hallucinations in all 
sensory 



modalities: auditory, visual, tactile, olfactory, and gustatory. 


Strong emotions, impulses, thoughts, and even speech or other actions may suddenly 
materialize, without 
a sense of personal 
ownership or control 
(i.e., lack of sense of agency). 
Conversely, thoughts and emotions may unexpectedly vanish, and speech and actions are 
abruptly inhibited. These experiences are frequently reported as ego-dystonic and puzzling. 
Attitudes, outlooks, and personal 
preferences (e.g., about 
food, activities, gender identity) may 
suddenly shift. Individuals may report 
that 
their bodies feel 
different 
(e.g., like a small 
child, the 
opposite gender, different 
ages simultaneously). Alterations in sense of self and agency may be 
accompanied by a feeling that 
attitudes, emotions, and behaviors even the individual s own 
body are  not 
mine  or are  not 
under my control.  Although most 
Criterion A symptoms are 
subjective, these sudden discontinuities in speech, affect, and behavior may be witnessed by 
family, friends, or the clinician. 


In most 
individuals with dissociative identity disorder, switching/shifting of states is subtle 
and may occur with only subtle changes in overt 
presentation. State switching may be more overt 
in the possession form 
of dissociative identity disorder. In general, the individual 
with 
dissociative identity disorder experiences himself or herself as multiple, simultaneously 
overlapping and interfering states. 


Dissociative amnesia (Criterion B) manifests in several 
major domains: 
1) gaps in any aspect 
of autobiographical 
memory (e.g., important 
life events like getting married or giving birth, lack 
of recall 
of all 
school 
experiences before high school); 
2) lapses in memory of recent 
events or 
well-learned skills (e.g., how to do one s job, use a computer, cook or drive); 
and 3) discovery of 
possessions that 
the individual 
has no recollection of ever owning (e.g., clothing, weapons, tools, 
writings or drawings that he or she must have created). 


332 


Dissociative fugues, with amnesia for travel, are common. Individuals may report 
suddenly 
finding themselves in another city, at 
work, or even at 
home: 
in the closet, under the bed, or 
running out 
of the house. Amnesia in individuals with dissociative identity disorder is not 
limited 
to stressful 
or traumatic events; 
it 
can involve everyday events as well. Individuals may report 
major gaps in ongoing memory (e.g., experiencing  time loss,   blackouts,  or  coming to  in 
the midst 
of doing something). Dissociative amnesia may be apparent 
to others (e.g., the 
individual does not recall something others witnessed that he or she did or said, cannot remember 
his or her own name, or may fail to recognize spouse, children, or close friends). Minimization or 
rationalization of amnesia is common. 


Possession-form 
identities in dissociative identity disorder typically manifest 
behaviorally as 
if a  spirit,  supernatural 
being, or outside person has taken control, with the individual 
speaking 
or acting in a distinctly different 
manner. For example, an individual s behavior may give the 
appearance that 
her identity has been replaced by the  ghost  of a girl 
who died by suicide in the 
same community years before, speaking and acting as though she were still 
alive. The identities 
that 
arise during possession-form 
dissociative identity disorder present 
recurrently, are unwanted 
and involuntary, and cause clinically significant 
distress or impairment 
(Criterion C). However, 
the majority of possession states that 
occur around the world are usually part 
of a broadly 
accepted cultural 
or religious practice and therefore do not 
meet 
criteria for dissociative identity 
disorder (Criterion D). 



Associated Features 


Individuals with dissociative identity disorder typically present 
with comorbid depression, 
anxiety, substance abuse, self-injury, or another common symptom. Nonepileptic seizures and 
other functional 
neurological 
symptoms are prominent 
in some presentations of dissociative 
identity disorder, especially in some non-Western settings. Some individuals, especially in 
Western settings, may present 
with apparently refractory neurological 
symptoms, such as 
headaches, seizures, or symptoms suggestive of multiple sclerosis. 


Individuals with dissociative identity disorder often conceal, 
or are not 
fully aware of, 
disruptions in consciousness, amnesia, or other dissociative symptoms. Many individuals with 
dissociative identity disorder report 
dissociative flashbacks during which they experience a 
sensory reliving of a previous event 
as though it 
were occurring in the present, often with a 
change of identity, a partial 
or complete loss of contact 
with or disorientation to current 
reality 
during the flashback, and a subsequent 
amnesia for the content 
of the flashback. Individuals with 
the disorder typically report 
multiple types of interpersonal 
maltreatment 
during childhood and 
adulthood. Other overwhelming early life events, such as multiple long, painful, early-life 
medical 
procedures, also may be reported. Nonsuicidal 
self-injury is frequent. On standardized 
measures, these individuals report 
higher levels of hypnotizability and dissociative symptoms 
compared with other clinical 
groups and healthy control 
subjects. Some individuals experience 
transient psychotic phenomena or episodes. 


Among personality features, avoidant 
personality features most 
often rate highest 
in 
individuals with dissociative identity disorder, and some individuals with dissociative identity 
disorder are so avoidant 
that 
they prefer to be alone. When decompensated, some individuals 
with dissociative identity disorder display features of borderline personality disorder (i.e., self-
destructive high-risk behaviors, and mood instability). Many individuals with dissociative 
identity disorder display attachment 
problems but 
typically do not 
exhibit 
frantic activity to 
avoid being abandoned. Some have stable long-term 
relationships, albeit 
frequently 
dysfunctional 
and/or abusive ones, from 
which they may have difficulty extricating themselves. 
Obsessional 
personality features are common in dissociative identity disorder, more so than 
histrionic personality features. A subgroup of 


333 


individuals with dissociative identity disorder have narcissistic and/or antisocial 
personality 
features. 


Prevalence 


The 12-month prevalence of dissociative identity disorder among adults in a small 
U.S. 
community study was 1.5%. Lifetime prevalence of dissociative identity disorder was 1.1% in a 
representative sample of community-based women in mid-eastern Turkey. 


Development and Course 


The disorder may first 
manifest 
at 
almost 
any age from 
early childhood to late life. Children 
usually do not 
present 
with identity shifting, instead presenting primarily with independently 
acting, imaginary companions, or as personified  mood  states (Criterion A phenomena). 



Dissociation in children may generate problems with memory, concentration, and attachment, 
and may be associated with traumatic play. In adolescents, dissociative identity disorder 
commonly comes to clinical 
attention because of externalizing symptoms, suicidal/selfdestructive 
behavior, or rapid behavioral 
shifts often ascribed to other disorders such as 
attention-deficit/hyperactivity disorder or childhood bipolar disorder. Some children with 
dissociative identity disorder can also be quite aggressive and irritable. Older individuals with 
dissociative identity disorder may present 
with symptoms that 
appear to be late-life mood 
disorders, obsessive-compulsive disorder, paranoia, psychotic mood disorders, or even cognitive 
disorders attributable to dissociative amnesia. 


Overt 
identity alteration/confusion may be triggered by many factors, such as later traumatic 
experiences (e.g., sexual 
assault), or even seemingly inconsequential 
stressors, like a minor 
motor vehicle accident. The experience of other major or cumulative life stressors may also 
worsen symptoms, including life events such as the individual s children reaching the same age 
at 
which the individual 
was significantly abused or traumatized. The death of, or the onset 
of a 
fatal 
illness in, the individual s abuser(s) is another example of an event 
that 
may worsen 
symptoms. Individuals with dissociative identity disorder are at 
high risk for adult 
interpersonal 
trauma such as rape, intimate partner violence, and sexual 
exploitation, including ongoing 
incestuous abuse into adulthood, as well as adult trafficking. 


Risk and Prognostic Factors 


Environmental. 
In the context 
of family and attachment 
pathology, early life trauma (e.g., neglect 
and physical, sexual, and emotional 
abuse, usually before ages 5 6 years) represents a risk factor 
for dissociative identity disorder. In studies from 
diverse geographic regions, about 
90% of the 
individuals with the disorder report 
multiple types of early neglect 
and childhood abuse, often 
extending into late adolescence. Some individuals report 
that 
maltreatment 
primarily occurred 
outside the family, in school, church, and/or neighborhoods, including being bullied severely. 
Other forms of repeated early-life traumatic experiences include multiple, painful 
childhood 
medical 
and surgical 
procedures; 
war; 
terrorism; 
or being trafficked beginning in childhood. 
Onset 
has also been described after prolonged and often transgenerational 
exposure to 
dysfunctional 
family dynamics (e.g., overcontrolling parenting, insecure attachment, emotional 
abuse) in the absence of clear neglect or sexual or physical abuse. 


Genetic 
and 
physiological. 
Twin studies suggest 
that 
genetics account 
for around 45% 50% of the 
interindividual 
variance in dissociative symptoms, with nonshared, stressful, and traumatic 
environmental 
experiences accounting for most 
of the additional 
variance. Several 
brain regions 
have been implicated in the pathophysiology of dissociative identity disorder, including the 
orbitofrontal cortex, hippocampus, parahippocampal gyrus, and amygdala. 


334 


Course 
modifiers. 
Ongoing sexual, physical, and emotional 
trauma often leads to significant 
difficulties in later functioning. Poorer outcome in adults is commonly related to severe 
psychosocial 
stressors, revictimization, ongoing sexual 
or physical 
abuse or exploitation, 
intimate partner violence, refractory substance use, eating disorders, severe medical 
illness, 
enmeshment 
with the individual s abusive family of origin, or ongoing involvement 
in criminal 



subgroups. Poorer functioning may also be related to perpetration of child maltreatment 
or 
intimate partner violence by individuals with dissociative identity disorder. 


Culture-Related Diagnostic Issues 


Many features of dissociative identity disorder can be influenced by the individual s 
sociocultural 
background. In settings where possession symptoms are common (e.g., rural 
areas 
in low- and middle-income countries, among certain religious groups in the United States and 
Europe), all 
or some of the fragmented identities may take the form 
of possessing spirits, deities, 
demons, animals, or mythical figures. Acculturation or prolonged intercultural contact may shape 
the presentation of the other identities (e.g., identities in India may speak English exclusively and 
wear Western clothes). Possession-form 
dissociative identity disorder can be distinguished from 
culturally accepted possession states in that 
the former is involuntary, distressing, and 
uncontrollable; 
involves conflict 
between the individual 
and his or her surrounding family, 
social, or work milieu; 
and is manifested at 
times and in places that 
violate cultural 
or religious 
norms. Combined dissociative-psychosis episodes may be more common in cultural 
contexts 
with marked communal violence or oppression and limited opportunity for redress. 


Sex- and Gender-Related Diagnostic Issues 


Women with dissociative identity disorder predominate in adult 
clinical 
settings but 
not 
in 
child/adolescent 
clinical 
settings or in general 
population studies. Few differences in symptom 
profiles, clinical 
history, and childhood trauma history have been found in comparisons between 
men and women with dissociative identity disorder, except 
that 
women may have higher rates of 
somatization. 


Association With Suicidal 
Thoughts or Behavior 


Suicidal 
behavior is frequent. Over 70% of outpatients with dissociative identity disorder have 
attempted suicide; 
multiple attempts are common, and other self-injurious and high-risk 
behaviors are highly prevalent. Individuals with dissociative identity disorder have multiple 
interacting risk factors for self-destructive and/or suicidal 
behavior. These include cumulative, 
severe early- and later-life trauma; 
high rates of comorbid posttraumatic stress disorder (PTSD), 
depressive disorders, and substance use disorders; 
and personality disorder features. Dissociation 
itself is an independent 
risk factor for multiple suicide attempts. Greater severity of dissociative 
symptom 
scores is associated with a higher frequency of suicide attempts and nonsuicidal 
self-
injury among individuals with dissociative disorders. 


Functional 
Consequences of Dissociative Identity Disorder 


Some children and adolescents with dissociative identity disorder may function poorly in school 
and in relationships. Others do well 
in school, experiencing it 
as a respite. In adults impairment 
varies widely, from apparently minimal (e.g., in high-functioning professionals) to profound. The 
symptoms of higher-functioning individuals may impair their relational, marital, family, and 
parenting functions more than their occupational 
and professional 
life, although the latter also 
may be affected. Many impaired individuals show improvement 
in occupational 
and personal 
functioning over time, while some individuals with dissociative 



335 


identity disorder may be impaired in most 
activities of living and function at 
the level 
of chronic 
and persistent mental illness. 


Differential 
Diagnosis 


Dissociative 
amnesia. 
Both dissociative identity disorder and dissociative amnesia are 
characterized by gaps in the recall 
of everyday events, important 
personal 
information, or 
traumatic events that 
are inconsistent 
with ordinary forgetting. Dissociative identity disorder is 
distinguished from 
dissociative amnesia by the additional 
presence of identity disruption 
characterized by two or more distinct personality states. 


Depersonalization/derealization 
disorder. 
The essential 
feature of depersonalization/derealization 
disorder is persistent 
or recurrent 
episodes of depersonalization, derealization, or both. 
Individuals with depersonalization/derealization disorder do not 
experience the presence of 
personality/identity states with alterations of self and agency, nor do they typically report 
dissociative amnesia. 


Major depressive 
disorder. 
Most 
individuals with dissociative identity disorder endorse a lifelong 
negative posttraumatic emotional 
state, often with childhood onset, and their symptoms may 
appear to meet 
the criteria for a major depressive episode. Moreover, posttraumatic reactivity to 
times of year when trauma occurred (anniversary reactions), primarily manifesting with more 
despondency, distress, and suicidal 
ideation, may also appear to be major depressive disorder, 
with seasonal 
pattern. However, individuals with major depressive disorder or persistent 
depressive disorder do not 
experience dissociative fluctuations in self and agency and 
dissociative amnesia. It 
is important 
to assess if all 
or most 
identity states are experiencing the 
adverse mood state, since mood disorder symptoms may fluctuate because they are experienced 
in some identity states, but not others. 


Bipolar disorders. 
Dissociative identity disorder is commonly misdiagnosed as bipolar disorder, 
typically bipolar II disorder, with mixed features. The relatively rapid shifts in behavioral 
state in 
individuals with dissociative identity disorder usually within minutes or hours are atypical for 
even the most 
rapid-cycling individuals with bipolar disorders. These state alterations are due to 
rapidly shifting dissociative states and/or fluctuating posttraumatic intrusions. Sometimes these 
shifts are accompanied by rapid changes in levels of activation, but 
these usually last 
minutes to 
hours, not 
days, and are associated with activation of specific identity states. Elevated or 
depressed mood may be experienced as loculated in specific identities, through 
overlap/interference phenomena. Usually, the individual 
with dissociative identity disorder does 
not 
have a classic bipolar sleep disturbance (e.g., reduced need for sleep), instead suffering from 
chronic, severe nightmares and nocturnal flashbacks that interrupt sleep. 


Posttraumatic 
stress 
disorder. 
A majority of individuals with dissociative identity disorder will 
have symptoms that 
meet 
diagnostic criteria for comorbid PTSD. Dissociative symptoms 
characteristic of dissociative identity disorder should be differentiated from 
the dissociative 
amnesia, dissociative flashbacks, and depersonalization/derealization characteristic of acute 
stress disorder, PTSD, or the dissociative subtype of PTSD. Dissociative amnesia in PTSD 
typically manifests only for specific traumatic events or aspects of traumatic events, as opposed 



to the chronic, complex dissociative amnesia characteristic of dissociative identity disorder. 
Depersonalization/derealization symptoms in the dissociative subtype of PTSD are related to 
specific posttraumatic reminders. Depersonalization/derealization symptoms in dissociative 
identity disorder may occur not 
only in response to posttraumatic reminders, but 
also in an 
ongoing fashion in daily life, including in response to stressful 
interpersonal 
interactions and 
when there is overlap/interference between states. 


Schizophrenia 
and 
other psychotic 
disorders. 
Individuals with dissociative identity disorder may 
experience symptoms that can superficially appear similar to those of psychotic 


336 


disorders. These include auditory hallucinations and symptoms characteristic of intrusions of 
personality states into the individual s awareness; 
these symptoms can seemingly resemble some 
of the Schneiderian first-rank symptoms formerly considered indicative of schizophrenia (e.g., 
thought 
broadcasting, thought 
insertion, thought 
withdrawal, hearing voices keeping up a 
running commentary about 
the individual). For example, hearing different 
personality states 
discussing the individual 
can resemble auditory hallucinations of voices arguing in 
schizophrenia. The individual 
with dissociative identity disorder may also experience the 
thoughts or emotions of an intruding personality state, which can resemble thought 
insertion in 
schizophrenia, as well 
as experience the sudden disappearance of these thoughts or emotions, 
which can resemble thought 
withdrawal. Such experiences in an individual 
with schizophrenia 
are usually accompanied by delusional 
beliefs about 
the cause of those symptoms (i.e., thoughts 
being inserted by an outside force), whereas individuals with dissociative identity disorder 
typically experience these symptoms as ego-alien and frightening. Individuals with dissociative 
identity disorder may also report 
a range of visual, tactile, olfactory, gustatory, and somatic 
hallucinations, which are usually related to autohypnotic, posttraumatic, and dissociative factors, 
such as partial 
flashbacks, in contrast 
to individuals with schizophrenia, whose hallucinations are 
primarily auditory and less commonly visual. Dissociative identity disorder and psychotic 
disorders are therefore distinguished by symptoms characteristic of one of these conditions and 
not 
the other (e.g., dissociative amnesia in dissociative identity disorder and not 
in psychotic 
disorders). Finally, individuals with schizophrenia have low hypnotic capacity, whereas 
individuals with dissociative identity disorder have the highest 
hypnotic capacity among all 
clinical groups. 


Substance/medication-induced 
disorders. 
Individuals with dissociative identity disorder frequently 
have a current 
or past 
history of substance use disorders. Symptoms associated with the 
physiological 
effects of a substance (e.g., blackouts) should be distinguished from 
dissociative 
amnesia in dissociative identity disorder if the substance in question is judged to be etiologically 
related to the memory loss. 


Personality 
disorders. 
Individuals with dissociative identity disorder often present 
identities that 
appear to encapsulate a variety of severe personality disorder features, suggesting a differential 
diagnosis of personality disorder, especially of the borderline type. Importantly, however, the 
individual s longitudinal 
variability in personality style (attributable to inconsistency among 
identities) differs from 
the pervasive and persistent 
dysfunction in affect 
management 
and 
interpersonal relationships typical of those with personality disorders. 



Posttraumatic 
amnesia 
due 
to 
brain 
injury. 
Both dissociative identity disorder and traumatic brain 
injury (TBI) are characterized by gaps in memory. Other characteristics of TBI include loss of 
consciousness, disorientation and confusion, or, in more severe cases, neurological 
signs and 
symptoms. A neurocognitive disorder due to TBI manifests either immediately after brain injury 
occurs or immediately after the individual 
recovers consciousness after the injury, and persists 
past 
the acute postinjury period. The cognitive presentation of a neurocognitive disorder 
following TBI is variable and includes difficulties in the domains of complex attention, executive 
function, and learning and memory, as well 
as slowed speed of information processing and 
disturbances in social 
cognition. While depersonalization is not 
uncommon following TBI, the 
additional 
neurocognitive features noted above help distinguish it 
from 
dissociative amnesia that 
is part 
of dissociative identity disorder. Moreover, dissociative amnesia occurring in the context 
of dissociative identity disorder is accompanied by a marked discontinuity in sense of self and 
sense of agency, which are not features of TBI. 
Functional 
neurological 
symptom disorder (conversion 
disorder). 
Functional 
neurological 
symptom 


disorder may be distinguished from 
dissociative identity disorder by the absence of identity 
alteration characterized by two or more distinct personality states or an 


337 


experience of possession. Dissociative amnesia in functional 
neurological 
symptom 
disorder is 


more limited and circumscribed (e.g., amnesia for a nonepileptic seizure). 
Factitious 
disorder and 
malingering. 
Individuals who feign dissociative identity disorder usually do 
not 
report 
the subtle symptoms of intrusion characteristic of the disorder; 
instead they tend to 
overreport 
media-based symptoms of the disorder, such as dramatic dissociative amnesia and 
melodramatic switching behaviors, while underreporting less-publicized comorbid symptoms, 
such as depression. Individuals who feign dissociative identity disorder tend to be relatively 
undisturbed by or may even seem 
to enjoy  having  the disorder, or may ask clinicians to  find  
traumatic memories. In contrast, most 
individuals with genuine dissociative identity disorder are 
ashamed of and overwhelmed by their symptoms, deny the diagnosis, underreport 
their 
symptoms, and display minimization and avoidance of their trauma history. 


Individuals who feign the symptoms of dissociative identity disorder usually create limited, 
stereotyped alternate identities, with feigned amnesia related only to the events for which gain is 
sought, with apparent 
switching behaviors and amnesia only displayed while being observed. 
They may present 
an  all-good  identity and an  all-bad  identity in hopes of gaining 
exculpation for a crime. 


Comorbidity 


Disorders that 
are comorbid with dissociative identity disorder include PTSD, depressive 
disorders, substance-related disorders, feeding and eating disorders, obsessive-compulsive 
disorder, antisocial 
personality disorder, and other specified personality disorder with avoidant, 
obsessive-compulsive, or borderline personality traits. The most 
common forms of functional 
neurological 
symptom 
disorder include nonepileptic seizures, gait 
disturbances, and paralyses. 
Most 
commonly, nonepileptic seizures resemble grand mal 
seizures or complex partial 
seizures 
with temporal lobe foci; others may mimic absence or partial seizures. 



Dissociative Amnesia 


Diagnostic Criteria 
F44.0 


A. 
An 
inability to 
recall important 
autobiographical information, 
usually of 
a 
traumatic or stressful nature, 
that 
is inconsistent 
with 
ordinary forgetting. 
Note: 
Dissociative 
amnesia 
most 
often 
consists of 
localized 
or selective 
amnesia 
for a 
specific event 
or events; 
or generalized 
amnesia 
for identity and 
life 
history. 


B. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
C. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
alcohol or other drug 
of 
abuse, 
a 
medication) or a 
neurological or other 
medical condition 
(e.g., 
partial complex seizures, 
transient 
global amnesia, 
sequelae 
of 
a 
closed 
head 
injury/traumatic brain 
injury, 
other neurological 
condition). 
D. 
The 
disturbance 
is not 
better explained 
by dissociative 
identity disorder, 
posttraumatic stress disorder, 
acute 
stress disorder, 
somatic symptom disorder, 
or major or mild 
neurocognitive 
disorder. 
Coding 
note: 
The 
code 
for dissociative 
amnesia 
without 
dissociative 
fugue 
is F44.0. 
The 
code 
for dissociative 
amnesia 
with 
dissociative 
fugue 
is F44.1. 


Specify 
if: 
F44.1 
With 
dissociative 
fugue: 
Apparently purposeful travel or bewildered 
wandering 
that 
is associated 
with 
amnesia 
for identity or for other important 
autobiographical information. 


338 


Specifiers 


The specifier  with dissociative 
fugue  applies when dissociative amnesia occurs in the context 
of a dissociative fugue, which is characterized by apparently purposeful 
travel 
or bewildered 
wandering that 
is associated with amnesia for identity or other important 
autobiographical 
information. 


Diagnostic Features 


The defining characteristic of dissociative amnesia is an inability to recall 
important 
autobiographical 
information that 
1) should be successfully stored in memory and 2) ordinarily 
would be freely recollected (Criterion A). Dissociative amnesia is conceptualized as a potentially 
reversible memory retrieval 
deficit. In this way, among others, it 
differs from 
the amnesias 
attributable to neurobiological damage or toxicity that impair memory storage or retrieval. 


A variety of types of dissociative amnesia may manifest. In general, the memory deficit 
in 



dissociative amnesia is retrograde 
and, except 
in rare cases, is not 
associated with ongoing 
amnesia for contemporary life events. Retrospective memory impairments 
include not 
only lost 
memories of traumatic experiences but 
also lost 
memories of everyday life during which no 
trauma occurred. Most 
commonly, individuals with dissociative amnesia report 
localized 
amnesia a failure to recall 
events during a circumscribed period of time; 
and/or selective 
amnesia the individual 
can recall 
some, but 
not 
all, of the events during a circumscribed period 
of time. In systematized amnesia 
the individual 
fails to recall 
a specific category of important 
information (e.g., fragmentary recall 
of home growing up, but 
continuous memory for school; 
no 
recall 
of a violent 
older sibling; 
lack of recall 
of a specific room 
in the individual s childhood 
home). Individuals rarely overtly complain of symptoms of these forms of dissociative amnesia 
and attempt to minimize and rationalize the memory loss. 


Generalized dissociative amnesia 
involves a complete loss of memory for most 
or all 
of the 
individual s life history. Individuals with generalized amnesia may forget 
personal 
identity (e.g., 
a woman loses memory of her entire life history after giving in to repeated pressure from 
a close 
friend to engage in a sexual 
relationship), lose previous knowledge about 
the world (e.g., recent 
political 
events, how to use current 
technology), and less commonly lack access to well-learned 
skills (e.g., what 
contact 
lenses are and how to put 
them 
in). Generalized dissociative amnesia 
has an acute onset; 
the perplexity, disorientation, and purposeless wandering of individuals with 
generalized amnesia usually bring them 
to the attention of the police or psychiatric emergency 
services. Dissociative fugue is commonly associated with generalized dissociative amnesia and 
can be indicated by using the  with dissociative fugue  specifier. Generalized dissociative 
amnesia may be more common among combat 
veterans, sexual 
assault 
victims, and individuals 
experiencing extreme emotional 
stress or conflict. In continuous amnesia (i.e., anterograde 
dissociative amnesia), an individual forgets each new event as it occurs. 


Individuals with dissociative amnesia are frequently unaware (or only partially aware) of 
their memory problems. They may recall 
some traumatic events, or parts of traumatic events, but 
not 
others of the same type. Many, especially those with localized amnesia, minimize the 
importance of their memory loss and may become uncomfortable when prompted to address it. 


Associated Features 


Many individuals with dissociative amnesia are chronically impaired in their ability to form 
and 
sustain satisfactory relationships. Histories of trauma, especially child abuse, and victimization 
are common. Some individuals with dissociative amnesia report 
dissociative flashbacks (i.e., 
behavioral reexperiencing of traumatic events). Many have a history of 


339 


nonsuicidal 
self-injury, suicide attempts, and other high-risk behaviors. Depressive and 
functional 
neurological 
symptoms are common, as are depersonalization, auto-hypnotic 
symptoms, and high hypnotizability. Sexual 
dysfunctions are common. Mild traumatic brain 
injury (TBI) may precede dissociative amnesia. 


Prevalence 


The 12-month prevalence for dissociative amnesia among adults in a small 
U.S. community 



study was 1.8%. 


Development and Course 


Dissociative amnesia has been observed in young children, adolescents, adults, and geriatric 
populations. Amnesia in children younger than 12 may be the most 
difficult 
to evaluate because 
they often have difficulty understanding questions about 
amnesia, and interviewers may find it 
difficult 
to formulate child-friendly questions about 
memory and amnesia, especially in younger 
children. Observations of apparent 
dissociative amnesia are often difficult 
to differentiate from 
inattention, absorption, daydreaming, anxiety, oppositional 
behavior, and learning disorders. 
Reports from 
several 
different 
sources (e.g., teacher, therapist, case worker) may be needed to 
diagnose amnesia in children. Some traumatized adolescents with dissociative amnesia are less 
likely to come to clinical 
attention because of lower levels of posttraumatic stress disorder 
(PTSD) intrusive symptoms and less externalizing behavior. Dissociative fugue behavior in 
children and adolescents may be limited by the child s life space (e.g., a child in a fugue  coming 
to  after bicycling to an unfamiliar neighborhood, a teenager finding herself having taken public 
transportation to a nearby town). 


Onset 
of generalized amnesia is usually sudden. Individuals may experience multiple 
episodes of this type of dissociative amnesia. A single episode may predispose to future 
episodes. In between episodes of amnesia, the individual 
may or may not 
appear to be acutely 
symptomatic. Some episodes of acute generalized amnesia resolve rapidly (e.g., when the 
individual 
is removed from 
combat 
or some other stressful 
situation, and/or is brought 
to clinical 
attention). A substantial 
subgroup of individuals develop highly impairing, debilitating, chronic 
autobiographical 
memory deficits, such that 
even  relearning  their life history does not 
ameliorate the memory loss. 


Removal 
from 
the traumatic circumstances generating acute, generalized dissociative 
amnesia (e.g., combat) may bring about 
a rapid return of memory. The memory loss of 
individuals with dissociative fugue may be particularly refractory. Later life trauma, life stresses, 
or losses may precede breakdown of long-standing autobiographical 
memory deficits related to 
childhood or adult 
trauma, with the onset 
of acute PTSD, mood disorders, substance abuse, and 
dangerousness to self or others, among other symptoms. 


Risk and Prognostic Factors 


Environmental. 


Severe, acute, or chronic traumatization is the main risk factor for dissociative 
amnesia. Cumulative early life trauma and adversities, especially physical 
and sexual 
abuse, are 
the major risk factors for dissociative amnesia for childhood and adolescence. More severe 
sexual 
abuse, multiple episodes of childhood sexual 
abuse, and sexual 
abuse by a relative, 
especially with betrayal 
by a close attachment 
figure, may increase the extent 
of childhood 
autobiographical 
memory disturbances. Individuals with dissociative amnesia may deny recall 
of 
specific childhood traumas (e.g., sexual 
assault), even those documented in medical 
or social 
service reports, although the individual 
can recall 
other similar traumatic events, both before and 
after the amnestic event. Severe cumulative adult 
trauma (e.g., repeated combat, trafficking, 
prisoner-of-war or concentration camp 


340 



experiences) also may result 
in extensive localized, selective, and/or systematized dissociative 
amnesia. Generalized dissociative amnesia may be more common among individuals who have 
recently experienced extreme acute traumas (e.g., brutal 
military combat, rape, torture, often in 
the context 
of inability to escape) and/or a prior history of major social 
dislocation, asylum-
seeking, or refugee status. Others develop generalized amnesia in the context 
of profound 
psychological 
conflict 
from 
which the individual 
also feels unable to escape. Virtually all 
individuals who develop generalized dissociative amnesia in the context 
of psychological 
conflict 
report 
past 
histories of severe early life and/or adult 
traumatization. Extreme acute 
traumatic experiences also may engender major psychological 
conflicts (e.g., a woman develops 
generalized amnesia after experiencing a brutal 
rape resulting in an unwanted pregnancy and 
becomes suicidal; 
on assessment, she reveals that 
her religion views abortion as murder and 
suicide as a major sin). 


Genetic 
and 
physiological. 
Quantitative genetic studies suggest 
that 
genetics account 
for about 
50% of the interindividual 
variance in dissociative symptoms, with nonshared, stressful 
environmental 
experiences accounting for most 
of the additional 
variance. Candidate gene 
studies suggest 
a gene x environment 
interplay with earlier and more chronic childhood 
traumatic experiences leading to significant increases in dissociative symptoms later in life. 


Culture-Related Diagnostic Issues 


In cultural 
contexts where possession is part 
of normative religious or spiritual 
practice, 
dissociative amnesia and fugue may be interpreted as resulting from 
pathological 
possession. In 
contexts or situations where individuals feel 
highly constrained by social 
circumstances or 
cultural 
traditions, the precipitants of dissociative amnesia often do not 
involve frank trauma. 
Instead, the amnesia may be preceded by severe psychological 
stresses or conflicts (e.g., marital 
conflict, other family disturbances, attachment 
problems, or conflicts attributable to restriction or 
oppression). 


Association With Suicidal 
Thoughts or Behavior 


Suicidal 
and other self-destructive behaviors are common in individuals with dissociative 
amnesia. The psychological 
forces producing generalized amnesia may be extreme, and suicidal 
thoughts, impulses, plans, and behavior are a risk when amnesia decreases. Case reports suggest 
that 
suicidal 
behavior may be a particular risk when the amnesia remits suddenly and 
overwhelms the individual with intolerable memories. 


Functional 
Consequences of Dissociative Amnesia 


Impairments in individuals with dissociative amnesia resulting from 
childhood/adolescent 
traumatization range from 
limited to severe. Some of these individuals may be chronically 
impaired in their ability to form 
and sustain satisfactory attachments. Some may become highly 
successful 
in occupational 
functioning but 
often do so by compulsive overwork. Individuals with 
acute generalized dissociative amnesia usually have impairment 
in all 
aspects of functioning. A 
substantial subgroup of individuals with generalized amnesia develop a highly impairing, chronic 
autobiographical 
memory deficit 
that 
even relearning their life history does not 
ameliorate. These 
individuals experience a highly debilitated, chronic course with poor overall 
functioning in most 



domains of life. 


Differential 
Diagnosis 


Dissociative 
identity 
disorder. 
Recurrent 
episodes of dissociative amnesia may be attributable to 
dissociative identity disorder. Individuals with dissociative amnesia may report depersonalization 
and auto-hypnotic symptoms, as do individuals with dissociative 


341 


identity disorder. Individuals with dissociative identity disorder report 
pervasive discontinuities 
in sense of self and agency, accompanied by many other dissociative symptoms. Amnesias in 
dissociative identity disorder, in addition to retrospective autobiographical 
memory deficits, 
include ongoing amnesia ( time loss ) for everyday events and interpersonal 
interactions; 
finding unexplained possessions; 
perplexing major fluctuations in skills and knowledge; 
and 
frequent, brief amnesic gaps during interpersonal interactions. 


Posttraumatic 
stress 
disorder. 
Some individuals with PTSD cannot 
recall 
part 
or all 
of a specific 
traumatic event 
(e.g., a rape victim 
who cannot 
recall 
most 
events for the entire day of the rape). 
When that 
amnesia extends to events beyond the immediate time of the trauma, a comorbid 
diagnosis of dissociative amnesia may be warranted. Individuals with the dissociative subtype of 
PTSD may also report dissociative amnesia in addition to depersonalization/derealization. 


Neurocognitive 
disorders. 
In major neurocognitive disorders, there is typically evidence of neural 
tissue damage accompanied by a decline in cognitive function with deficits in attention, 
executive function, learning and memory, language, and perceptual-motor and social 
cognition 
that 
impair capacity for independent 
everyday activities. Memory loss for personal 
information is 
usually embedded in cognitive, linguistic, affective, attentional, and behavioral 
disturbances. 
Generally, awareness of personal 
identity is spared until 
late in the course of the neurocognitive 
disorder. In neurocognitive disorders, retrograde amnesia is almost 
always accompanied by 
anterograde amnesia. Anterograde dissociative amnesia can be confused with delirium. However, 
medical, laboratory, toxicological, and neurological 
workups, including imaging studies, are 
normal. Careful, repeated evaluations over time will 
show that 
as in other forms of dissociative 
amnesia, there are no true neurocognitive deficits. 


Substance-related 
disorders. 
In the context 
of repeated intoxication with alcohol 
or other 
substances/medications, there may be episodes of  blackouts  or periods for which the individual 
has no memory, or partial 
memory ( grayouts ). To aid in distinguishing these episodes from 
dissociative amnesia, a longitudinal 
history should show that 
the amnestic episodes occur only in 
the context 
of intoxication. However, the distinction may be difficult 
when the individual 
with 
dissociative amnesia also misuses alcohol 
or other substances, particularly in the context 
of 
stressful 
situations that 
may also exacerbate dissociative symptoms. This can be a more complex 
differential 
diagnosis when the substance use begins in childhood or adolescence, generally in 
the context 
of intrafamilial 
abuse, neglect, and substance-related disorders. Sequential 
observation of these individuals after detoxification, along with carefully taken history, usually 
can distinguish the memory loss attributable to long-standing substance use from 
dissociative 
amnesia. Some individuals with comorbid dissociative amnesia and substance use disorders will 
attempt 
to minimize their dissociative amnesia and attribute memory problems solely to the 



substance use. Prolonged use of alcohol 
or other substances may result 
in a substance-induced 
neurocognitive disorder that 
may be associated with impaired cognitive function. However, in 
this context 
the protracted history of substance use and the persistent 
deficits associated with the 
neurocognitive disorder would serve to distinguish it 
from 
dissociative amnesia, where there is 
typically no evidence of persistent impairment in intellectual functioning. 


Posttraumatic 
amnesia 
due 
to 
brain 
injury. 
Amnesia may occur in the context 
of a TBI when there 
has been an impact 
to the head or other mechanisms of rapid movement 
or displacement 
of the 
brain within the skull. Other characteristics of TBI include loss of consciousness, disorientation 
and confusion, or, in more severe cases, neurological 
signs and symptoms (e.g., abnormalities on 
neuroimaging, a new onset 
of seizures or a marked worsening of a preexisting seizure disorder, 
visual 
field cuts, anosmia). A neurocognitive disorder attributable to TBI must 
present 
either 
immediately after brain injury occurs or immediately after the individual 
recovers consciousness 
after the injury, and persist past the 


342 


acute postinjury period. The cognitive presentation of a neurocognitive disorder following TBI is 
variable and includes difficulties in the domains of complex attention, executive function, 
learning and memory, as well 
as slowed speed of information processing and disturbances in 
social 
cognition. The patterns of memory deficits are typical 
of neurocognitive disorders. Mild 
TBI may precede acute dissociative amnesia presentations, but 
the dissociative memory deficits 
are out 
of proportion to the TBI head trauma and typically follow the dissociative, not 
the 
neurocognitive, patterns. 


Seizure 
disorders. 
Individuals with seizure disorders may exhibit 
complex behavior during 
seizures or postictally with subsequent 
amnesia. Some individuals with a seizure disorder engage 
in nonpurposive wandering that 
is limited to the period of seizure activity. Conversely, behavior 
during a dissociative fugue is usually purposeful, complex, and goal-directed and may last 
for 
days, weeks, or longer. Occasionally, individuals with a seizure disorder will 
report 
that 
some 
autobiographical 
memories have been  wiped out  as the seizure disorder progresses. Such 
memory loss is not 
associated with psychological 
trauma or adversities and appears to occur 
randomly. In seizure disorders, serial 
electroencephalograms usually show abnormalities. 
Telemetric electroencephalographic monitoring generally shows an association between the 
episodes of amnesia and seizure activity. Dissociative and epileptic amnesias may coexist. 
Memory 
deficits 
associated 
with 
electroconvulsive 
therapy. 
Memory deficits after electroconvulsive 


therapy (ECT) most 
commonly occur for the day of ECT 
administration. More extensive 
retrograde and even anterograde amnesia after ECT 
is usually unrelated to stressful 
or traumatic 
life epochs, and generally remits after the ECT 
series concludes. ECT 
in severely depressed 
individuals with dissociative disorders does not 
worsen dissociation, and memory access may 
improve as depression remits. 


Catatonic 
stupor. 
Mutism 
in catatonic stupor may suggest 
dissociative amnesia, but 
failure of 
recall 
is usually absent. Other catatonic symptoms (e.g., rigidity, posturing, negativism) are 
usually present. Catatonic symptoms in children can be associated with trauma, abuse, and/or 
deprivation. Unlike in dissociative amnesia, the pattern of memory loss in catatonia is only for 
the catatonic episode. 



Acute 
dissociative 
reactions 
to 
stressful 
events 
(other specified 
dissociative 
disorder). 


The acute 
dissociative reactions to stressful 
events example of other specified dissociative disorder is 
characterized by a combination of dissociative symptoms that 
occur together acutely in response 
to stressful 
events and typically last 
less than 1 month. Amnestic episodes that 
occur as part 
of 
these reactions are accompanied by other prominent 
dissociative symptoms, have a short 
duration (hours or days), and tend to be circumscribed to limited periods or events in a person s 
life (micro-amnesias). 


Factitious 
disorder and 
malingering. 
There is no test, battery of tests, or set 
of procedures that 
invariably distinguishes dissociative amnesia from 
feigned amnesia. Feigned amnesia is more 
common in individuals with 1) acute, florid dissociative amnesia; 
2) financial, sexual, or legal 
problems; 
3) a wish to escape stressful 
circumstances; 
4) a desire to seem 
to be a more 
interesting patient; 
and/or 5) a plan to engage in litigation for  recovered memories.  However, 
dissociative amnesia can be associated with those same circumstances and can coexist 
with 
deliberate feigning. Many individuals who malinger amnesia confess spontaneously or when 
confronted. 
Memory 
changes 
with 
aging 
or mild 
neurocognitive 
disorder. 
Memory decrements in mild 


neurocognitive disorder differ from 
those of dissociative amnesia; 
in mild neurocognitive 
disorder, memory changes manifest 
as difficulty in learning and retaining new information. This 
is often measured in tests of verbal 
learning of word lists or a brief story with evaluation of 
immediate and delayed recall. With normal 
cognitive aging, individuals may also have similar 
weaknesses in immediate and delayed recall of new information, 


343 


although normal 
aging may also affect 
information processing speed and other complex 
executive function tasks in addition to memory. 


Comorbidity 


As is common in individuals with a history of trauma, many comorbidities co-occur with 
dissociative amnesia, particularly as dissociative amnesia begins to remit. A wide variety of 
affective phenomena may surface, including dysphoria, grief, rage, shame, guilt, and 
psychological 
conflict 
and turmoil. Individuals may engage in nonsuicidal 
self-injury and other 
high-risk behaviors. These individuals may have symptoms that 
meet 
diagnostic criteria for 
persistent 
depressive disorder, major depressive disorder, or subthreshold depression (other 
specified depressive disorder). Many individuals with dissociative amnesia develop PTSD at 
some point 
during their life, especially when the traumatic antecedents of their amnesia are 
brought 
into conscious awareness. Many of these individuals may show symptoms of the 
dissociative subtype of PTSD. Many individuals with dissociative amnesia have symptoms that 
meet 
diagnostic criteria for a comorbid somatic symptom 
and related disorder (and vice versa), 
particularly functional 
neurological 
symptom 
disorder (conversion disorder). Substance-related 
and addictive disorders may be comorbid with dissociative amnesia, as well 
as feeding and 
eating disorders and sexual 
dysfunctions. The most 
common comorbid personality disorder is 
other specified personality disorder (with mixed personality disorder features), which often 
includes avoidant, obsessive-compulsive, dependent, and borderline features. 



Depersonalization/Derealization 
Disorder 


Diagnostic Criteria 
F48.1 


A. 
The 
presence 
of 
persistent 
or recurrent 
experiences of 
depersonalization, 
derealization, 
or both: 
1. 
Depersonalization: 
Experiences of 
unreality, 
detachment, 
or being 
an 
outside 
observer with 
respect 
to 
one s thoughts, 
feelings, 
sensations, 
body, 
or 
actions (e.g., 
perceptual alterations, 
distorted 
sense 
of 
time, 
unreal or absent 
self, 
emotional and/or physical numbing). 
2. 
Derealization: 
Experiences of 
unreality or detachment 
with 
respect 
to 
surroundings (e.g., 
individuals or objects are 
experienced 
as unreal, 
dreamlike, 
foggy, 
lifeless, 
or visually distorted). 
B. 
During 
the 
depersonalization 
or derealization 
experiences, 
reality testing 
remains 
intact. 
C. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
D. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
medication) or another medical condition 
(e.g., 
seizures). 
E. 
The 
disturbance 
is not 
better explained 
by another mental disorder, 
such 
as 
schizophrenia, 
panic disorder, 
major depressive 
disorder, 
acute 
stress disorder, 
posttraumatic stress disorder, 
or another dissociative 
disorder. 
Diagnostic Features 


The essential 
features of depersonalization/derealization disorder are persistent 
or recurrent 
episodes of depersonalization, derealization, or both. Episodes of depersonalization are 
characterized by a feeling of unreality or detachment 
from, or unfamiliarity with, the individual s 
whole self or from 
aspects of the self (Criterion A1). The individual 
may feel 
detached from 
his 
or her entire being (e.g.,  I am no one,   I have no self ). He or she may 


344 


also feel 
subjectively detached from 
aspects of the self, including feelings (e.g., 
hypoemotionality: 
 I know I have feelings, but 
I don t 
feel 
them ), thoughts (e.g.,  My thoughts 
don t feel like my own,   head filled with cotton ), whole body or body parts, or sensations (e.g., 
touch, proprioception, hunger, thirst, libido). There may also be a diminished sense of agency 
(e.g., feeling robotic, like an automaton; 
lacking control 
of speech or movements). The 
depersonalization experience can sometimes be one of a split 
self, with one part 
observing and 
one participating, known as an  out-of-body experience  in its most 
extreme form. The unitary 
symptom 
of  depersonalization  consists of several 
symptom 
factors: 
anomalous body 
experiences (i.e., unreality of the self and perceptual 
alterations); 
emotional 
or physical 
numbing; 



and temporal distortions with anomalous subjective recall. 


Episodes of derealization are characterized by a feeling of unreality or detachment 
from, or 
unfamiliarity with, the world, be it 
individuals, inanimate objects, or all 
surroundings (Criterion 
A2). The individual 
may feel 
as if he or she were in a fog, dream, or bubble, or as if there were a 
veil 
or a glass wall 
between the individual 
and the world around. Surroundings may be 
experienced as artificial, colorless, or lifeless. Derealization is commonly accompanied by 
subjective visual 
distortions, such as blurriness, heightened acuity, widened or narrowed visual 
field, two-dimensionality or flatness, exaggerated three-dimensionality, or altered distance or 
size of objects (i.e., macropsia or micropsia). Auditory distortions can also occur, whereby 
voices or sounds are muted or heightened. In addition, Criterion C 
requires that 
the symptoms 
cause clinically significant 
distress or impairment 
in social, occupational, or other important 
areas of functioning, and Criteria D and E describe exclusionary diagnoses. 


Associated Features 


Individuals with depersonalization/derealization disorder may have difficulty describing their 
symptoms and may think they are  crazy  or  going crazy.  Another common experience is the 
fear of irreversible brain damage. A commonly associated symptom 
is a subjectively altered 
sense of time (i.e., too fast 
or too slow), as well 
as a subjective difficulty in vividly recalling past 
memories and owning them 
as personal 
and emotional. Vague somatic symptoms, such as head 
fullness, tingling, or lightheadedness, are not 
uncommon. Individuals may experience extreme 
rumination or obsessional 
preoccupation (e.g., constantly obsessing about 
whether they really 
exist, or checking their perceptions to determine whether they appear real). Varying degrees of 
anxiety and depression are also common associated features. Individuals with the disorder have 
been found to have physiological 
hyporeactivity to emotional 
stimuli. Neural 
substrates of 
interest 
include the hypothalamic-pituitary-adrenocortical 
axis, inferior parietal 
lobule, and 
prefrontal cortical-limbic circuits. 


Prevalence 


Transient 
depersonalization/derealization symptoms lasting hours to days are common in the 
general 
population. The 12-month prevalence of depersonalization/derealization disorder is 
thought 
to be markedly less than for transient 
symptoms, although precise estimates for the 
disorder are unavailable. In general, approximately one-half of all 
adults have experienced at 
least 
one lifetime episode of depersonalization/derealization. However, symptomatology that 
meets full 
criteria for depersonalization/derealization disorder is markedly less common than 
transient symptoms. One-month prevalence in the United Kingdom is approximately 1% 2%. 


Development and Course 


The mean age at 
onset 
of depersonalization/derealization disorder is 16 years, although the 
disorder can start 
in early or middle childhood; 
a minority cannot 
recall 
ever not 
having had the 
symptoms. Less than 20% of individuals experience onset 
after age 20 years and only 5% after 
age 25 years. Onset in the fourth decade of life or later is highly unusual. 


345 



Onset 
can range from 
extremely sudden to gradual. Duration of depersonalization/derealization 
disorder episodes can vary greatly, from 
brief (hours or days) to prolonged (weeks, months, or 
years). Given the rarity of disorder onset 
after age 40 years, in such cases the individual 
should 
be examined more closely for underlying medical 
conditions (e.g., brain lesions, seizure 
disorders, sleep apnea). The course of the disorder is often persistent. About 
one-third of cases 
involve discrete episodes; 
another third, continuous symptoms from 
the start; 
and still 
another 
third, an initially episodic course that eventually becomes continuous. 


While in some individuals the intensity of symptoms can wax and wane considerably, others 
report 
an unwavering level 
of intensity that 
in extreme cases can be constantly present 
for years 
or decades. Internal 
and external 
factors that 
affect 
symptom 
intensity vary between individuals, 
yet 
some typical 
patterns are reported. Exacerbations can be triggered by stress, worsening mood 
or anxiety symptoms, novel 
or overstimulating settings, and physical 
factors such as lighting or 
lack of sleep. 


Risk and Prognostic Factors 


Temperamental. 
Individuals with depersonalization/derealization disorder are characterized by 
harm-avoidant 
temperament, immature defenses, and both disconnection and overconnection 
schemata. Immature defenses such as idealization/devaluation, projection, and acting out 
result 
in denial 
of reality and poor adaptation. Cognitive disconnection schemata 
reflect 
defectiveness 
and emotional inhibition and subsume themes of abuse, neglect, and deprivation. Overconnection 
schemata 
involve impaired autonomy with themes of dependency, vulnerability, and 
incompetence. 


Environmental. 
There is a clear association between the disorder and childhood interpersonal 
traumas in a substantial 
portion of individuals, although this association is not 
as prevalent 
or as 
extreme in the nature of the traumas as in other dissociative disorders, such as dissociative 
identity disorder. In particular, emotional 
abuse and emotional 
neglect 
have been most 
strongly 
and consistently associated with the disorder. Other stressors can include physical 
abuse; 
witnessing domestic violence; 
growing up with a seriously impaired, mentally ill 
parent; 
or 
unexpected death or suicide of a family member or close friend. Sexual 
abuse is a much less 
common antecedent 
but 
can be encountered. The most 
common proximal 
precipitants of the 
disorder are severe stress (interpersonal, financial, occupational), depression, anxiety 
(particularly panic attacks), and illicit 
drug use. Symptoms may be specifically induced by 
substances such as tetrahydrocannabinol, hallucinogens, ketamine, MDMA (3,4methylenedioxymethamphetamine; 
 ecstasy ), and salvia. Marijuana use may precipitate new-
onset panic attacks and depersonalization/derealization symptoms simultaneously. 


Culture-Related Diagnostic Issues 


Volitionally induced experiences of depersonalization/derealization can be a part 
of meditative 
practices that 
are prevalent 
in many religious, spiritual, and cultural 
contexts and should not 
be 
diagnosed as a disorder. However, there are individuals who initially induce these states 
intentionally but 
over time lose control 
over them 
and may develop a fear and aversion for 
related practices. Cultural 
frameworks may affect 
the level 
of distress or perceived severity 
associated with uncontrolled depersonalization/derealization experiences by providing 
explanations for them 
(e.g., spiritual/supernatural 
causes), which may alleviate individuals  fears 



that they are  losing their mind.  


Functional 
Consequences of Depersonalization/Derealization Disorder 


Symptoms of depersonalization/derealization disorder are highly distressing and are associated 
with major morbidity. The affectively flattened and robotic demeanor that these 


346 


individuals often demonstrate may appear incongruent 
with the extreme emotional 
pain reported 
by those with the disorder. Impairment 
is often experienced in both interpersonal 
and 
occupational spheres, largely as a result of the hypoemotionality with others, subjective difficulty 
in focusing and retaining information, and a general sense of disconnectedness from life. 


Differential 
Diagnosis 


Illness 
anxiety 
disorder. 
Although individuals with depersonalization/derealization disorder can 
present 
with vague somatic complaints as well 
as fears of permanent 
brain damage, the diagnosis 
of depersonalization/derealization disorder is characterized by the presence of a constellation of 
typical 
depersonalization/derealization symptoms and the absence of other manifestations of 
illness anxiety disorder. 


Major depressive 
disorder. 
Feelings of numbness, deadness, apathy, and being in a dream 
are not 
uncommon in major depressive episodes. However, in depersonalization/derealization disorder, 
such symptoms are associated with further symptoms of the disorder. If the 
depersonalization/derealization clearly precedes the onset 
of a major depressive episode or 
clearly continues after its resolution, the diagnosis of depersonalization/derealization disorder 
applies. 


Obsessive-compulsive 
disorder. 
Some individuals with depersonalization/derealization disorder 
can become obsessively preoccupied with their subjective experience or develop rituals checking 
on the status of their symptoms. However, other symptoms of obsessive-compulsive disorder 
unrelated to depersonalization/derealization are not present. 


Other dissociative 
disorders. 
In order to diagnose depersonalization/derealization disorder, the 
symptoms should not 
occur in the context 
of another dissociative disorder, such as dissociative 
identity disorder. Differentiation from 
dissociative amnesia and functional 
neurological 
symptom 
disorder (conversion disorder) is simpler, as the symptoms of these disorders do not 
overlap with 
those of depersonalization/derealization disorder. 


Panic 
attacks. 
Depersonalization/derealization is one of the symptoms of panic attacks, 
increasingly common as panic attack severity increases. Therefore, 
depersonalization/derealization disorder should not 
be diagnosed when the symptoms occur only 
during panic attacks that 
are part 
of panic disorder, social 
anxiety disorder, or specific phobia. In 
addition, it 
is not 
uncommon for depersonalization/derealization symptoms to first 
begin in the 
context 
of new-onset 
panic attacks or as panic disorder progresses and worsens. In such 
presentations, the diagnosis of depersonalization/derealization disorder can be made if 1) the 
depersonalization/derealization component 
of the presentation is very prominent 
from 
the start, 
clearly exceeding in duration and intensity the occurrence of actual 
panic attacks; 
or 2) the 



depersonalization/derealization continues after panic disorder has remitted or has been 


successfully treated. 
Psychotic 
disorders. 
The presence of intact 
reality testing specifically regarding the 
depersonalization/derealization symptoms is essential 
to differentiating 
depersonalization/derealization disorder from 
psychotic disorders. Rarely, positive-symptom 
schizophrenia can pose a diagnostic challenge when nihilistic delusions are present. For example, 
an individual 
may complain that 
he or she is dead or the world is not 
real; 
this could be either a 
subjective experience that the individual knows is not true or a delusional conviction. 


Substance/medication-induced 
disorders. 
Depersonalization/derealization associated with the 
physiological 
effects of substances during acute intoxication or withdrawal 
is not 
diagnosed as 
depersonalization/derealization disorder. The most 
common precipitating substances are the 
illicit drugs marijuana, hallucinogens, ketamine, ecstasy, and salvia. In 


347 


about 
15% of all 
cases of depersonalization/derealization disorder, the symptoms are precipitated 
by ingestion of such substances. If the symptoms persist 
for some time in the absence of any 
further substance or medication use, the diagnosis of depersonalization/derealization disorder 
applies. This diagnosis is usually easy to establish since the vast 
majority of individuals with this 
presentation become highly phobic and aversive to the triggering substance and do not 
use it 
again. 


Traumatic 
brain 
injury. 
Depersonalization/derealization symptoms are typical 
in traumatic brain 
injury (TBI) but 
are distinguished from 
depersonalization/derealization disorder by onset 
of 
symptoms following TBI and the lack of other symptoms of depersonalization/derealization 
disorder. 
Dissociative 
symptoms 
due 
to 
another medical 
condition. 
Features such as onset 
after age 40 years or 


the presence of atypical 
symptoms and course in any individual 
suggest 
the possibility of an 
underlying medical 
condition. In cases with dissociative symptoms, it 
is essential 
to conduct 
a 
thorough medical 
and neurological 
evaluation, which may include standard laboratory studies, 
viral 
titers, an electroencephalogram, vestibular testing, visual 
testing, sleep studies, and/or brain 
imaging. When the suspicion of an underlying seizure disorder proves difficult 
to confirm, an 
ambulatory electroencephalogram 
may be indicated; 
although temporal 
lobe epilepsy is most 
commonly implicated, parietal and frontal lobe epilepsy may also be associated. 


Comorbidity 


In a convenience sample of adults recruited for a number of depersonalization research studies, 
lifetime comorbidities were high for unipolar depressive disorder and for any anxiety disorder, 
with a significant 
proportion of the sample having both disorders. Comorbidity with 
posttraumatic stress disorder was low. The three most 
commonly co-occurring personality 
disorders were avoidant, borderline, and obsessive-compulsive. 


Other Specified 
Dissociative Disorder 



F44.89 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
dissociative 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
dissociative 
disorders diagnostic class. 
The 
other specified 
dissociative 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific dissociative 
disorder. 
This is done 
by recording 
 other specified 
dissociative 
disorder  followed 
by the 
specific reason 
(e.g., 
 dissociative 
trance ). 


Examples of 
presentations that 
can 
be 
specified 
using 
the 
 other specified  
designation 
include 
the 
following: 


1. 
Chronic 
and 
recurrent syndromes 
of mixed 
dissociative 
symptoms: 
This 
category includes identity disturbance 
associated 
with 
less-than-marked 
discontinuities in 
sense 
of 
self 
and 
agency, 
or alterations of 
identity or episodes 
of 
possession 
in 
an 
individual who 
reports no 
dissociative 
amnesia. 
2. 
Identity 
disturbance 
due 
to 
prolonged 
and 
intense 
coercive 
persuasion: 
Individuals who 
have 
been 
subjected 
to 
intense 
coercive 
persuasion 
(e.g., 
brainwashing, 
thought 
reform, 
indoctrination 
while 
captive, 
torture, 
long-term 
political imprisonment, 
recruitment 
by sects/cults or by terror organizations) may 
present 
with 
prolonged 
changes in, 
or conscious questioning 
of, 
their identity. 
348 


3. 
Acute 
dissociative 
reactions 
to 
stressful 
events: 
This category is for acute, 
transient 
conditions that 
typically last 
less than 
1 
month, 
and 
sometimes only a 
few hours or days. 
These 
conditions are 
characterized 
by constriction 
of 
consciousness; 
depersonalization; 
derealization; 
perceptual disturbances (e.g., 
time 
slowing, 
macropsia); 
microamnesias; 
transient 
stupor; 
and/or alterations in 
sensory-motor functioning 
(e.g., 
analgesia, 
paralysis). 
4. 
Dissociative 
trance: 
This condition 
is characterized 
by an 
acute 
narrowing 
or 
complete 
loss of 
awareness of 
immediate 
surroundings that 
manifests as 
profound 
unresponsiveness or insensitivity to 
environmental stimuli. 
The 
unresponsiveness may be 
accompanied 
by minor stereotyped 
behaviors (e.g., 
finger movements) of 
which 
the 
individual is unaware 
and/or that 
he 
or she 
cannot 
control, 
as well as transient 
paralysis or loss of 
consciousness. 
The 
dissociative 
trance 
is not 
a 
normal part 
of 
a 
broadly accepted 
collective 
cultural 
or religious practice. 
Unspecified 
Dissociative Disorder 



F44.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
dissociative 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
dissociative 
disorders diagnostic class. 
The 
unspecified 
dissociative 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific 
dissociative 
disorder and 
includes presentations for which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room settings). 



349 



Somatic Symptom and Related Disorders 


This chapter 
includes the diagnoses of somatic symptom 
disorder, illness anxiety disorder, 
functional 
neurological 
symptom 
disorder (conversion disorder), psychological 
factors affecting 
other medical 
conditions, factitious disorder, other specified somatic symptom 
and related 
disorder, and unspecified somatic symptom 
and related disorder. All 
of the disorders in this 
chapter share a common feature: 
the prominence of somatic symptoms and/or illness anxiety 
associated with significant 
distress and impairment. Individuals with disorders with prominent 
somatic symptoms or illness anxiety are commonly encountered in primary care and other 
medical 
settings but 
are less commonly encountered in psychiatric and other mental 
health 
settings. These reconceptualized diagnoses, based on a reorganization of DSM-IV somatoform 
disorder diagnoses, are more useful 
for primary care and other medical 
(nonpsychiatric) 
clinicians. 


The major diagnosis in this diagnostic class, somatic symptom 
disorder, emphasizes 
diagnosis made on the basis of the presence of symptoms and signs (distressing somatic 
symptoms plus abnormal 
thoughts, feelings, and behaviors in response to these symptoms) rather 
than the absence of a medical 
explanation for somatic symptoms. A distinctive characteristic of 
many individuals with somatic symptom 
disorder is not 
the somatic symptoms per se, but 
instead 
the way they present 
and interpret 
them. Incorporating affective, cognitive, and behavioral 
components into the criteria for somatic symptom 
disorder provides a more comprehensive and 
accurate reflection of the true clinical 
picture than can be achieved by assessing the somatic 
complaints alone. 


The principles behind the changes in the somatic symptom 
and related diagnoses from 
DSMIV 
are crucial 
in understanding the DSM-5 diagnoses. The DSM-IV term 
somatoform disorders 
was confusing and was replaced by somatic symptom and related disorders. In DSM-IV there 
was a great 
deal 
of overlap across the somatoform 
disorders and a lack of clarity about 
the 
boundaries of diagnoses. Although individuals with these disorders primarily present 
in medical 
rather than mental 
health settings, nonpsychiatric physicians found the DSM-IV somatoform 
diagnoses difficult 
to understand and use. The current 
DSM-5 classification recognizes this 
overlap by reducing the total number of disorders as well as their subcategories. 


The previous criteria overemphasized the centrality of symptoms being unexplained by 
recognized pathophysiological 
processes. Such symptoms are present 
to various degrees, 
particularly in functional 
neurological 
symptom 
disorder, but 
somatic symptom 
disorders can 
also accompany recognized medical 
conditions (i.e., those disorders related to clearly recognized 
pathophysiological 
processes). The reliability of determining that 
a somatic symptom 
is 
unexplained by a recognized pathophysiological 
process related to a recognized medical 
condition is limited, and grounding a diagnosis on the absence of an explanation is problematic 
and reinforces mind-body dualism. It 
is not 
appropriate to give an individual 
a mental 
disorder 
diagnosis solely because a recognized medical 
condition cannot 
be demonstrated. Furthermore, 



the presence of a recognized medical 
condition does not 
exclude the possibility of a comorbid 
mental 
disorder, including a somatic symptom 
and related disorder. Perhaps because of the 
predominant 
focus on lack of medical 
explanation in DSM-IV, individuals regarded these 
diagnoses as pejorative and demeaning, 


350 


implying that 
their physical 
symptoms were not 
 real.  The DSM-5 classification defines the 
major diagnosis, somatic symptom 
disorder, on the basis of positive symptoms (distressing 
somatic symptoms plus abnormal 
thoughts, feelings, and behaviors in response to these 
symptoms). In functional 
neurological 
symptom 
disorder and pseudocyesis (other specified 
somatic symptom 
and related disorder), the emphasis is on demonstrating clinical 
evidence of 
incompatibility with recognized pathophysiological processes. 


It 
is important 
to note that 
some other mental 
disorders may initially manifest 
with primarily 
somatic symptoms (e.g., major depressive disorder, panic disorder). Such diagnoses may account 
for the somatic symptoms, or they may occur alongside one of the somatic symptom 
and related 
disorders in this chapter. There is also considerable medical 
comorbidity among individuals with 
somatic symptom 
and related disorders. Although somatic symptoms are frequently associated 
with psychological 
distress and psychopathology, some somatic symptom 
and related disorders 
can arise spontaneously, and their causes can remain obscure. Anxiety disorders and depressive 
disorders may accompany somatic symptom 
and related disorders. The somatic component 
adds 
severity and complexity to depressive and anxiety disorders and results in higher severity, 
functional 
impairment, and even refractoriness to traditional 
treatments. In rare instances, the 
degree of preoccupation may be so severe as to warrant 
consideration of a delusional 
disorder 
diagnosis. 


A number of factors may contribute to somatic symptom 
and related disorders. These include 
genetic and biological 
vulnerability (e.g., increased sensitivity to pain), early traumatic 
experiences (e.g., violence, abuse, deprivation), medical 
iatrogenesis (e.g., reinforcement 
of the 
sick role, excessive referrals and diagnostic testing), and learning (e.g., lack of reinforcement 
of 
nonsomatic expressions of distress), as well 
as sociocultural 
norms that 
minimize or stigmatize 
psychological 
suffering as compared with physical 
suffering. Differences in medical 
care across 
cultural 
contexts affect 
the presentation, recognition, and management 
of these somatic 
presentations. Variations in symptom 
presentation are likely the result 
of the interaction of 
multiple factors within cultural 
contexts that 
affect 
how individuals identify and classify bodily 
sensations, perceive illness, and seek medical attention for them. 


All 
of these disorders are characterized by the prominent 
focus on somatic concerns and their 
initial 
presentation mainly in medical 
rather than mental 
health care settings. Somatic symptom 
disorder and illness anxiety disorder offer more clinically useful 
methods of characterizing 
individuals who may have been considered in the past 
for a diagnosis of somatization disorder 
and hypochondriasis. Furthermore, approximately two-thirds to three-fourths of individuals 
previously diagnosed with hypochondriasis are subsumed under the diagnosis of somatic 
symptom 
disorder. However, the remaining one-quarter to one-third of individuals with 
previously diagnosed hypochondriasis have high health anxiety in the absence of somatic 
symptoms, and many such individuals  symptoms would not 
qualify for an anxiety disorder 
diagnosis. The DSM-5 diagnosis of illness anxiety disorder is for this latter group of individuals. 



Illness anxiety disorder can be considered either a somatic symptom 
and related disorder or an 
anxiety disorder. Because of the strong focus on somatic concerns, and because illness anxiety 
disorder is most 
often encountered in medical 
settings, for utility it 
is listed with the somatic 
symptom 
and related disorders. In functional 
neurological 
symptom 
disorder, the key to 
diagnosis is neurological 
symptoms that 
can be demonstrated, on the basis of positive clinical 
examination features, to be incompatible with recognized pathophysiology. This is now a  rulein  
diagnosis, and not 
a diagnosis of exclusion, and can be made in the presence of a recognized 
neurological 
disorder. It 
no longer requires the presence of a recent 
psychological 
stressor, 
because such stressors are not 
always present. Psychological 
factors affecting other medical 
conditions is also included in this chapter. Its essential 
feature is the presence of one or more 
clinically significant psychological or behavioral factors that adversely affect a medical condition 
by increasing the risk for suffering, death, or disability. Like the other somatic symptom 
and 
related disorders, factitious disorder embodies persistent 
problems related to illness perception 
and identity. In the great majority of reported cases of factitious disorder, both 


351 


imposed on self and imposed on another, individuals present 
with somatic symptoms and 
expressed medical 
disease conviction. Consequently, DSM-5 factitious disorder is included 
among the somatic symptom 
and related disorders. Other specified somatic symptom 
and related 
disorder and unspecified somatic symptom 
and related disorder include conditions for which 
some, but 
not 
all, of the criteria for somatic symptom 
disorder or illness anxiety disorder are met, 
as well as pseudocyesis. 


Somatic Symptom Disorder 


Diagnostic Criteria 
F45.1 


A. 
One 
or more 
somatic symptoms that 
are 
distressing 
or result 
in 
significant 
disruption 
of 
daily life. 
B. 
Excessive 
thoughts, 
feelings, 
or behaviors related 
to 
the 
somatic symptoms or 
associated 
health 
concerns as manifested 
by at 
least 
one 
of 
the 
following: 
1. 
Disproportionate 
and 
persistent 
thoughts about 
the 
seriousness of 
one s 
symptoms. 
2. 
Persistently high 
level of 
anxiety about 
health 
or symptoms. 
3. 
Excessive 
time 
and 
energy devoted 
to 
these 
symptoms or health 
concerns. 
C. 
Although 
any one 
somatic symptom may not 
be 
continuously present, 
the 
state 
of 
being 
symptomatic is persistent 
(typically more 
than 
6 
months). 
Specify 
if: 
With 
predominant pain 
(previously pain 
disorder): 
This specifier is for 
individuals whose 
somatic symptoms predominantly involve 
pain. 



Specify 
if: 
Persistent: 
A 
persistent 
course 
is characterized 
by severe 
symptoms, 
marked 
impairment, 
and 
long 
duration 
(more 
than 
6 
months). 


Specify 
current 
severity: 
Mild: 
Only one 
of 
the 
symptoms specified 
in 
Criterion 
B 
is fulfilled. 
Moderate: 
Two 
or more 
of 
the 
symptoms specified 
in 
Criterion 
B 
are 
fulfilled. 
Severe: 
Two 
or more 
of 
the 
symptoms specified 
in 
Criterion 
B 
are 
fulfilled, 
plus 


there 
are 
multiple 
somatic complaints (or one 
very severe 
somatic symptom). 


Diagnostic Features 


Individuals with somatic symptom 
disorder typically have multiple, current, somatic symptoms 
that 
are distressing or result 
in significant 
disruption of daily life (Criterion A), although 
sometimes only one severe symptom, most 
commonly pain, is present. Symptoms may be 
specific (e.g., localized pain) or relatively nonspecific (e.g., fatigue). The symptoms sometimes 
represent 
normal 
bodily sensations or discomfort 
that 
does not 
generally signify serious disease. 
Somatic symptoms without 
an evident 
medical 
explanation are not 
sufficient 
to make this 
diagnosis. The individual s suffering is authentic, whether or not it is medically explained. 


The symptoms may or may not 
be associated with another medical 
condition. The diagnoses 
of somatic symptom 
disorder and a concurrent 
medical 
illness are not 
mutually exclusive, and 
these frequently occur together. For example, an individual 
may become seriously disabled by 
symptoms of somatic symptom 
disorder after an uncomplicated myocardial 
infarction even if the 
myocardial 
infarction itself did not 
result 
in any disability. If another medical 
condition or high 
risk for developing one is present 
(e.g., strong family history), the thoughts, feelings, and 
behaviors associated with this condition are excessive (Criterion B). 


352 


Individuals with somatic symptom 
disorder tend to have very high levels of worry about 
illness (Criterion B). They appraise their bodily symptoms as unduly threatening, harmful, or 
troublesome and often think the worst 
about 
their health. Even when there is evidence to the 
contrary, some individuals still 
fear the medical 
seriousness of their symptoms. In severe somatic 
symptom 
disorder, health concerns may assume a central 
role in the individual s life, becoming a 
feature of his or her identity and dominating interpersonal relationships. 


Individuals typically experience distress that 
is principally focused on somatic symptoms and 
their significance. When asked directly about 
their distress, some individuals describe it 
in 
relation to other aspects of their lives, while others deny any source of distress other than the 
somatic symptoms. Health-related quality of life is often impaired, both physically and mentally. 
The diagnosis can further be specified by stating whether complaints predominantly involve pain 
and/or if complaints are marked by a persistent course. 


Additionally, severity of somatic symptom 
disorder can be specified by the number of 
fulfilled B 
criteria. Mild forms of somatic symptom 
disorder (one symptom 
as specified in 
Criterion B 
is fulfilled) are more prevalent, while moderate (two or more B 
criteria are present) 
and severe cases (two or more symptoms as specified in Criterion B 
are fulfilled in combination 



with multiple somatic complaints or one very severe somatic symptom) are marked by higher 
levels of impairment. In severe somatic symptom 
disorder, the impairment 
is marked, and when 
persistent, the disorder can lead to invalidism. 


There is often a high level 
of medical 
care utilization, which rarely alleviates the individual s 
concerns. Consequently, the individual 
may seek care from 
multiple doctors for the same 
symptoms. These individuals often seem 
unresponsive to medical 
interventions, and new 
interventions may only exacerbate the presenting symptoms. Some individuals with the disorder 
seem 
unusually sensitive to medication side effects. Some feel 
that 
their medical 
assessment 
and 
treatment have been inadequate. 


The criteria for somatic symptom 
disorder appear suitable for use in children and 
adolescents, but they have been less studied in youth than among adults. 


Associated Features 


Cognitive features include attention focused on somatic symptoms, attribution of normal 
bodily 
sensations to physical 
illness (possibly with catastrophic interpretations), worry about 
illness, a 
self-concept 
of bodily weakness, and intolerance of bodily complaints. Besides health anxiety, 
emotional 
features may include negative affectivity, desperation, and demoralization related to 
somatic symptoms. The relevant 
associated behavioral 
features may include repeated bodily 
checking for abnormalities, repeated seeking of medical 
help and reassurance, and avoidance of 
physical 
activity. These behavioral 
features are most 
pronounced in severe, persistent 
somatic 
symptom 
disorder. These features are usually associated with frequent 
requests for medical 
help 
for different 
somatic symptoms. This may lead to medical 
consultations in which individuals are 
so focused on their concerns about 
somatic symptom(s) that 
they cannot 
be redirected to other 
matters. Any reassurance by the doctor that 
the symptoms are not 
indicative of serious physical 
illness tends to be short-lived and/or is experienced by the individuals as the doctor not 
taking 
their symptoms with due seriousness. As the focus on somatic symptoms is a primary feature of 
the disorder, individuals with somatic symptom 
disorder typically present 
to general 
medical 
health services rather than mental 
health services. The suggestion of referral 
to a mental 
health 
specialist 
may be met 
with surprise or even frank refusal 
by individuals with somatic symptom 
disorder. 


Prevalence 


The prevalence of somatic symptom 
disorder is unclear. Estimates about 
the prevalence of 
somatic symptom disorder come from the limited epidemiological literature on 


353 


DSM-IV-TR 
somatoform 
disorders. However, the prevalence of somatic symptom 
disorder is 
expected to be higher than that 
of the more restrictive DSM-IV-TR 
somatization disorder (<1%) 
but 
lower than that 
of undifferentiated somatoform 
disorder (approximately 19%). More recent 
population-based studies with a questionnaire-based strategy using DSM-5 diagnostic criteria for 
somatic symptom 
disorder in adult 
and adolescent 
samples report 
prevalence rates between 6.7% 
and 17.4%. Based on research conducted in Europe and North America, the prevalence of 
somatic symptom disorder in the general adult population can be approximated as 4% 6%. 



Somatic symptom disorder has a higher frequency in primary care patients than in the general 
population. Based on reviews and meta-analyses of studies from 
multiple countries that 
had still 
used DSM-IV or ICD-10 criteria, a 12-month prevalence of somatic symptom 
disorder and 
related conditions in primary care patients between 10% and 20% appears plausible. Prevalence 
rates are higher in clinical 
settings that 
specialize in psychosomatic or functional 
disorders, with 
reported frequencies of somatic symptom disorder between 40% and 60%. 


Women tend to report 
more somatic symptoms than do men, and the prevalence of somatic 
symptom disorder is consequently likely to be higher in women. 


Development and Course 


In a study of Danish children ages 5 7 years, functional 
somatic symptoms were common health 
complaints, which for a significant 
minority (roughly one-fifth) of those with complaints were 
severe enough to cause distress, impairment, school 
absences, or medical 
help-seeking. Age at 
onset does not seem to affect the duration of untreated illness. 


The course of somatic symptom 
disorder is likely to be chronic and fluctuating and 
influenced by the number of symptoms, individual s age, level 
of impairment, and any 
comorbidity. The course is also influenced by personality traits, with less harm 
avoidance and 
greater cooperativeness associated with a shorter time to remission. 


In children, the most 
common symptoms are recurrent 
abdominal 
pain, headache, fatigue, 
and nausea. A single prominent 
symptom 
is more common in children than in adults. When the 
diagnosis is being made in younger individuals, it 
is important 
to obtain patient, family, and 
other assessments (e.g., school) of symptom 
presentation. Patient 
and caregiver engagement 
during evaluation and management 
is fundamental 
because parents  interpretation of and 
response to symptoms may determine the level 
of associated distress, the demands for medical 
investigations and interventions, and time away from school. 


In older individuals, pain localized in several 
body regions appears to be the most 
common 
symptom. Somatic symptoms and concurrent 
medical 
illnesses are common as multimorbidity 
increases with age. Prevalence rates of somatic symptom 
disorder seem 
to be stable until 
age 65 
years and might 
decrease thereafter. For making the diagnosis in older individuals, a focus on the 
requirement 
for excessive thoughts, feelings, or behaviors related to the somatic symptoms or 
associated health concerns (Criterion B) is crucial. Somatic symptom 
disorder may be 
underdiagnosed in older adults either because certain somatic symptoms (e.g., pain, fatigue) are 
considered part 
of normal 
aging or because illness worry is considered  understandable  in older 
adults who have more general medical illnesses and medications than do younger people. 


Risk and Prognostic Factors 


Temperamental. 
The personality trait 
of negative affectivity (neuroticism) has been identified as 
an independent 
correlate/risk factor of a high number of somatic symptoms. Comorbid anxiety or 
depression is common and may exacerbate symptoms and impairment. 


354 


Environmental. 
Somatic symptom 
disorder is more frequent 
in individuals with few years of 
education and low socioeconomic status, and in those who have recently experienced stressful 
or 



health-related life events. Early lifetime adversity such as childhood sexual 
abuse is also likely a 


risk factor for somatic symptom disorder in adults. 
Course 
modifiers. 
Persistent 
somatic symptoms are associated with demographic features 
(women, older age, fewer years of education, lower socioeconomic status, unemployment), a 
reported history of sexual 
abuse or other childhood adversity, concurrent 
chronic physical 
illness 
or mental 
disorder (depression, anxiety, persistent 
depressive disorder, panic), social 
stress, and 
reinforcing social 
factors such as illness benefits. Total 
somatic symptom 
severity is probably 
associated with female gender, anxiety, depression and general 
medical 
illness. Cognitive factors 
that 
affect 
clinical 
course include sensitization to pain, heightened attention to bodily sensations, 
and attribution of bodily symptoms to a possible medical 
illness rather than recognizing them 
as 
a normal phenomenon or psychological stress. 


Culture-Related Diagnostic Issues 


High numbers of somatic symptoms are found in population-based and primary care studies 
around the world, with a similar pattern of the most 
commonly reported somatic symptoms, 
impairment, and treatment 
seeking. The relationship between number of somatic symptoms and 
illness worry is similar in different 
cultural 
contexts, and marked illness worry is associated with 
impairment 
and greater treatment 
seeking cross-culturally. In many cultural 
contexts, individuals 
with depression commonly present with somatic symptoms. 


Despite these similarities, there are differences in somatic symptoms across cultural 
contexts 
and ethnoracial 
groups. Sociocultural 
factors, particularly stigma related to mental 
disorders, 
may explain differences in somatic symptom 
reporting across cultural 
contexts. The description 
of somatic symptoms varies with linguistic and other local 
cultural 
factors. These somatic 
presentations have been described as  idioms of distress  because somatic symptoms may have 
special 
meanings and shape patient-clinician interactions in the particular cultural 
contexts. For 
example, sensations of heaviness, complaints of  gas,  too much heat 
in the body, or burning in 
the head are common in some cultures or ethnic groups but 
rare in others. Cultural 
explanations 
also vary, and somatic symptoms may be attributed variously to particular family, work (e.g., 
burnout), or other environmental 
stresses; 
general 
medical 
illness; 
the suppression of feelings of 
anger and resentment; 
or certain culturally specific attributions, such as semen loss. Certain 
somatic symptoms may be part 
of specific explanatory models in a given cultural 
context; 
for 
example, traditional 
understandings of shenjing shuairuo 
in China link concepts of  weakness of 
nerves  (neurasthenia) and hot-cold imbalance with prominent 
symptoms such as fatigue and 
low energy. There may also be differences in medical 
treatment 
seeking and utilization of 
nonmedical, traditional, alternative and complementary healing practices among cultural 
groups, 
in addition to differences due to variable access to medical 
care services. Cultural 
beliefs, 
previous illnesses, insurance status, health literacy, and health care experiences can influence 
individuals  perception of somatic symptoms and health care use. Seeking treatment 
for multiple 
somatic symptoms in general medical clinics is a worldwide phenomenon. 


Sex- and Gender-Related Diagnostic Issues 


In population-based studies, women report 
more somatic symptoms than men, and in one study 
of primary care patients with chronic pain, women reported more severe somatic symptoms than 
men. While exposure to sexual 
trauma, intimate partner violence, and a childhood trauma history 



is associated with increased somatic symptom expression in 


355 


both women and men, a childhood history of multiple adverse childhood experiences is 
especially likely to increase somatic symptom expression in women. 


In women, gender is associated with an increased likelihood of developing persistent 
symptoms of somatic symptom 
disorder. There appears to be no evidence that 
gender is 
associated with the duration of untreated illness and response to psychological 
or 
pharmacological treatment. 


Association With Suicidal 
Thoughts or Behavior 


Somatic symptom 
disorder is associated with suicidal 
thoughts and suicide attempts. It 
is likely 
that 
suicidal 
thoughts and behaviors are partly explained by the diagnostic overlap and frequent 
comorbidity of somatic symptom 
disorder and depressive disorders. In addition, dysfunctional 
illness perceptions and the severity of somatic symptoms appear to be independently associated 
with an increased risk of suicidal ideation. 


Functional 
Consequences of Somatic Symptom Disorder 


The disorder is associated with marked impairment 
of health status and high psychological 
distress. Many individuals with severe somatic symptom 
disorder are likely to have impaired 
health status scores more than 2 standard deviations below population norms. Health status is 
particularly impaired in the presence of multiple or severe symptoms. 


Differential 
Diagnosis 


If the somatic symptoms are consistent 
with another mental 
disorder (e.g., panic disorder), and 
the diagnostic criteria for that 
disorder are fulfilled, then that 
mental 
disorder should be 
considered as an alternative or additional 
diagnosis. If, as commonly occurs, the criteria for both 
somatic symptom 
disorder and another mental 
disorder diagnosis are fulfilled, then both should 
be diagnosed, as both may require treatment. 


Other medical 
conditions. 
The presence of somatic symptoms of unclear etiology is not 
in itself 
sufficient 
to make the diagnosis of somatic symptom 
disorder. The symptoms of many 
individuals with disorders like irritable bowel 
syndrome or fibromyalgia would not 
satisfy the 
criterion necessary to diagnose somatic symptom 
disorder (Criterion B). Conversely, the 
presence of somatic symptoms of an established medical 
condition (e.g., diabetes or heart 
disease) does not 
exclude the diagnosis of somatic symptom 
disorder if the criteria are otherwise 
met. Factors that 
distinguish individuals with somatic symptom 
disorder from 
individuals with 
general 
medical 
conditions alone include the ineffectiveness of analgesics, a history of mental 
disorders, unclear provocative or palliative factors, persistence without cessation, and stress. 
Psychological 
factors 
affecting 
other medical 
conditions. 
The diagnosis of somatic symptom 
disorder 


requires distressing or impairing somatic symptoms that 
may or may not 
be associated with 
another medical 
condition but 
must 
be accompanied by excessive or disproportionate thoughts, 
feelings, or behaviors related to the somatic symptoms or associated health concerns. In contrast, 



the diagnosis of psychological 
factors affecting other medical 
conditions requires the presence of 
a medical 
condition, as well 
as psychological 
factors that 
adversely affect 
its course or interfere 
with its treatment. 


Panic 
disorder. 
In panic disorder, somatic symptoms and anxiety about 
health tend to occur in 
acute episodes, whereas in somatic symptom 
disorder, anxiety and somatic symptoms are more 
persistent. 


Generalized 
anxiety 
disorder. 
Individuals with generalized anxiety disorder worry about 
multiple 
events, situations, or activities, only one of which may involve their health. The main focus is not 
usually somatic symptoms or fear of illness as it is in somatic symptom disorder. 


356 


Depressive 
disorders. 
Depressive disorders are commonly accompanied by somatic symptoms 
such as fatigue, headaches, or joint, abdominal, or other pains. However, depressive disorders are 
differentiated from 
somatic symptom 
disorder by the requirement 
of the presence of depressed 
mood or, in the case of major depressive disorder, either depressed mood or decreased interest 
or 
pleasure in activities. In some cultural 
contexts, these core symptoms of depression may be 
initially denied or deemphasized by individuals whose presentations would otherwise meet 
criteria for a depressive disorder. Such individuals might 
instead emphasize somatic symptoms 
that may be idiomatic (e.g., heavy heart) and unfamiliar to clinicians. 


Illness 
anxiety 
disorder. 


If the individual 
has extensive worries about 
health but 
no or minimal 
somatic symptoms, it may be more appropriate to consider illness anxiety disorder. 
Functional 
neurological 
symptom disorder (conversion 
disorder). 
In functional 
neurological 
symptom 


disorder, the presenting symptom 
is loss of function (e.g., of a limb), whereas in somatic 
symptom 
disorder, the focus is on the distress that 
particular symptoms cause. The features listed 
under Criterion B 
of somatic symptom 
disorder may be helpful 
in differentiating the two 
disorders. 


Delusional 
disorder. 
In somatic symptom 
disorder, the individual s beliefs that 
somatic symptoms 
might 
reflect 
serious underlying physical 
illness are not 
held with delusional 
intensity. 
Nonetheless, the individual s beliefs concerning the somatic symptoms can be firmly held. In 
contrast, in delusional 
disorder, somatic type, the individual s conviction that 
the somatic 
symptoms are indicative of having a serious underlying illness is stronger than that 
found in 
somatic symptom disorder. 


Body 
dysmorphic 
disorder. 
In body dysmorphic disorder, the individual 
is excessively concerned 
about, and preoccupied by, a perceived defect 
in his or her physical 
appearance. In contrast, in 
somatic symptom 
disorder, the concern about 
somatic symptoms reflects fear of underlying 
illness, not of a defect in appearance. 


Obsessive-compulsive 
disorder. 
In somatic symptom 
disorder, the recurrent 
ideas about 
somatic 
symptoms or illness are less intrusive, and individuals with this disorder do not 
exhibit 
the 
associated repetitive behaviors aimed at 
reducing anxiety that 
occur in obsessive-compulsive 
disorder. 


Factitious 
disorder and 
malingering. 
In factitious disorder and malingering, individuals present 
themselves as ill 
or impaired but 
have falsified presenting physical 
signs and symptoms with the 



intent 
to deceive. In contrast, the symptoms of somatic symptom 
disorder are not 
simulated or 
self-induced, and these individuals suffer authentically and seriously from 
their somatic 
complaints. 


Comorbidity 


Somatic symptom 
disorder is associated with high rates of comorbidity with other mental 
disorders as well 
as general 
medical 
conditions. The most 
relevant 
co-occurring mental 
disorders 
are anxiety and depressive disorders, each of which occurs in up to 50% of cases of somatic 
symptom 
disorders and significantly contributes to overall 
functional 
impairment 
and poorer 
quality of life. Other mental 
disorders that 
have been found to co-occur with somatic symptom 
disorder are posttraumatic stress disorder and obsessive-compulsive disorder. Other evidence 
indicates an association with sexual dysfunction in men. 


Elevated levels of the psychological 
features (Criterion B) of somatic symptom 
disorder have 
been found in several 
general 
medical 
conditions. When a concurrent 
general 
medical 
condition 
is present, the degree of impairment 
is more marked than would be expected from 
the physical 
illness alone. Moreover, somatization in medical 
illness has been shown to worsen disease and 
treatment outcomes, adherence, and quality of life and to increase health care utilization. 


357 


Illness Anxiety Disorder 


Diagnostic Criteria 
F45.21 


A. 
Preoccupation 
with 
having 
or acquiring 
a 
serious illness. 
B. 
Somatic symptoms are 
not 
present 
or, 
if 
present, 
are 
only mild 
in 
intensity. 
If 
another medical condition 
is present 
or there 
is a 
high 
risk for developing 
a 
medical condition 
(e.g., 
strong 
family history is present), 
the 
preoccupation 
is 
clearly excessive 
or disproportionate. 
C. 
There 
is a 
high 
level of 
anxiety about 
health, 
and 
the 
individual is easily alarmed 
about 
personal health 
status. 
D. 
The 
individual performs excessive 
health-related 
behaviors (e.g., 
repeatedly 
checks his or her body for signs of 
illness) or exhibits maladaptive 
avoidance 
(e.g., 
avoids doctor appointments and 
hospitals). 
E. 
Illness preoccupation 
has been 
present 
for at 
least 
6 
months, 
but 
the 
specific 
illness that 
is feared 
may change 
over that 
period 
of 
time. 
F. 
The 
illness-related 
preoccupation 
is not 
better explained 
by another mental 
disorder, 
such 
as somatic symptom disorder, 
panic disorder, 
generalized 
anxiety 
disorder, 
body dysmorphic disorder, 
obsessive-compulsive 
disorder, 
or 
delusional disorder, 
somatic type. 
Specify 
whether: 



Care-seeking 
type: 
Medical care, 
including 
physician 
visits or undergoing 
tests 
and 
procedures, 
is frequently used. 
Care-avoidant type: 
Medical care 
is rarely used. 


Diagnostic Features 


Most 
individuals who previously would have been diagnosed with hypochondriasis in DSM-IV 
(preoccupation with having a serious disease based on the individual s misinterpretation of 
bodily symptoms) are now classified as having somatic symptom 
disorder; 
however, in one-third 
of cases, the diagnosis of illness anxiety disorder applies instead. 


Illness anxiety disorder entails a preoccupation with having or acquiring a serious, 
undiagnosed medical 
illness (Criterion A). Somatic symptoms are not 
present 
or, if present, are 
only mild in intensity (Criterion B). A thorough evaluation fails to identify a serious medical 
condition that 
accounts for the individual s concerns. While the concern may be derived from 
a 
nonpathological 
physical 
sign or sensation, the individual s distress emanates not 
primarily from 
the physical 
complaint 
itself but 
rather from 
his or her anxiety about 
the meaning, significance, 
or cause of the complaint 
(i.e., the suspected medical 
diagnosis). If a physical 
sign or symptom 
is 
present, it 
is often a normal 
physiological 
sensation (e.g., orthostatic dizziness), a benign and 
self-limited dysfunction (e.g., transient 
tinnitus), or a bodily discomfort 
not 
generally considered 
indicative of disease (e.g., belching). If a diagnosable medical 
condition is present, the 
individual s anxiety and preoccupation are clearly excessive and disproportionate to the severity 
of the condition (Criterion B). Most 
empirical 
evidence and existing literature pertain to 
previously defined DSM hypochondriasis and health anxiety, and it 
is unclear to what 
extent 
and 
how precisely they apply to the description of this new diagnosis. 


The preoccupation with the idea that 
one is sick is accompanied by substantial 
anxiety about 
health and disease (Criterion C). Individuals with illness anxiety disorder are easily alarmed 
about 
illness, such as by hearing about 
someone else falling ill 
or reading a health-related news 
story. Their concerns about 
undiagnosed disease do not 
respond to appropriate medical 
reassurance, negative diagnostic tests, or benign course. The physician s attempts at 
reassurance 
and symptom palliation generally do not alleviate the individual s 


358 


concerns and may heighten them. Illness concerns assume a prominent 
place in the 
individual s life, affecting daily activities, and may even result 
in invalidism. Illness becomes a 
central 
feature of the individual s identity and self-image, a frequent 
topic of social 
discourse, 
and a characteristic response to stressful 
life events. Individuals with the disorder often examine 
themselves repeatedly (e.g., examining one s throat 
in the mirror) (Criterion D). They research 
their suspected disease excessively (e.g., on the Internet) and repeatedly seek reassurance from 
family, friends, or physicians. This incessant 
worrying often becomes frustrating for othe rs and 
may result 
in considerable strain within the family. In some cases, the anxiety leads to 
maladaptive avoidance of situations (e.g., visiting sick family members) or activities (e.g., 
exercise) that these individuals fear might jeopardize their health. 



Associated Features 


Because they believe they are medically ill, individuals with illness anxiety disorder are 
encountered far more frequently in medical 
than in mental 
health settings. The majority of 
individuals with illness anxiety disorder have extensive yet 
unsatisfactory medical 
care. They 
generally have elevated rates of utilization of medical 
and mental 
health services compared with 
the general 
population. In a minority of cases of illness anxiety disorder, individuals are too 
anxious to seek medical attention and avoid medical health care. 


They often consult 
multiple physicians for the same problem 
and obtain repeatedly negative 
diagnostic test 
results. At 
times, medical 
attention leads to a paradoxical 
exacerbation of anxiety 
or to iatrogenic complications from 
diagnostic tests and procedures. Individuals with the disorder 
are generally dissatisfied with their medical 
care and find it 
unhelpful, often feeling they are not 
being taken seriously by physicians. At 
times, these concerns may be justified, since physicians 
sometimes are dismissive or respond with frustration or hostility. This response can occasionally 
result in a failure to diagnose a medical condition that is present. 


Prevalence 


Prevalence estimates of illness anxiety disorder are based on estimates of the DSM-III and DSMIV 
diagnosis hypochondriasis 
and health anxiety. The 1- to 2-year prevalence of health anxiety 
and/or disease conviction in community surveys and population-based samples from 
high-
income countries such as the United States and Germany ranges from 
1.3% to 10%. In 
ambulatory medical 
populations, the 6-month/1-year prevalence rates are between 2.2% and 8% 
across a range of countries, with weighted mean prevalence rates of 3%. By contrast, in a study 
of patients in specialty clinics, about 
one-fifth of individuals reported illness anxiety. The 
prevalence of the disorder is similar in men and women. 


Development and Course 


The development 
and course of illness anxiety disorder are unclear. Illness anxiety disorder is 
generally thought 
to be a chronic, episodic, and relapsing condition with an age at 
onset 
in early 
and middle adulthood. The disorder is thought 
to be rare in children, although the onset 
of 
health-related anxieties can occur in childhood or adolescence. In some population-based 
samples, health-related anxiety increases with age, but 
in others, health anxiety peaks in middle 
age, before declining in older age. The ages of individuals with high health anxiety in medical 
settings do not 
appear to differ from 
those of other individuals in those settings. In older 
individuals, health-related anxiety often focuses on memory loss and sensory loss. 


Risk and Prognostic Factors 


Environmental. 
Illness anxiety disorder may sometimes be precipitated by a major life stress or a 
serious but ultimately benign threat to the individual s health. A history of 


359 


childhood abuse or of a serious childhood illness, serious illness in a parent, or death of an ill 
parent during childhood may predispose to development of the disorder in adulthood. 



Course 
modifiers. 
Approximately one-third to one-half of individuals with illness anxiety 
disorder have a transient 
form, which is associated with less 
psychiatric comorbidity, more 
medical comorbidity, and less severe illness anxiety disorder. 


Culture-Related Diagnostic Issues 


The diagnosis should be made with caution in individuals whose ideas about 
disease are 
congruent 
with widely held cultural 
beliefs. The prevalence appears to be similar across different 
countries, although little is known about the cross-cultural variation in phenomenology. 


Functional 
Consequences of Illness Anxiety Disorder 


Illness anxiety disorder causes substantial 
role impairment 
and decrements in physical 
function 
and health-related quality of life. Health concerns often interfere with interpersonal 
relationships, 
disrupt family life, and damage occupational performance. 


Differential 
Diagnosis 


Other medical 
conditions. 
The first 
differential 
diagnostic consideration is an underlying medical 
condition, including neurological 
or endocrine conditions, occult 
malignancies, and other 
diseases that 
affect 
multiple body systems. The presence of a medical 
condition does not 
rule out 
the possibility of coexisting illness anxiety disorder. If a medical 
condition is present, the health-
related anxiety and disease concerns are clearly disproportionate to its seriousness. Transient 
preoccupations related to a medical condition do not constitute illness anxiety disorder. 


Adjustment 
disorders. 
Health-related anxiety is a normal 
response to serious illness and is not 
a 
mental 
disorder. Such nonpathological 
health anxiety is clearly related to the medical 
condition 
and is typically time-limited. If the health anxiety is severe enough to cause clinically significant 
distress or impairment 
in one or more important 
areas of functioning, an adjustment 
disorder 
may be diagnosed. However, if disproportionate health-related anxiety persists for longer than 6 
months, a diagnosis of illness anxiety disorder may apply. 


Somatic 
symptom disorder. 
Both somatic symptom 
disorder and illness anxiety disorder may be 
characterized by a high level 
of anxiety about 
health and excessive health-related behaviors. 
They are differentiated by the fact 
that 
somatic symptom 
disorder requires the presence of 
somatic symptoms that 
are distressing or result 
in significant 
disruption of daily life, whereas in 
illness anxiety disorder, somatic symptoms either are not 
present 
or, if present, are only mild in 
intensity. 


Anxiety 
disorders. 
In generalized anxiety disorder, individuals worry about 
multiple events, 
situations, or activities, only one of which may involve health. In panic disorder, the individual 
may be concerned that 
the panic attacks reflect 
the presence of a medical 
illness; 
however, 
although these individuals may have health anxiety, their anxiety is typically very acute and 
episodic. In illness anxiety disorder, the health anxiety and fears are more persistent 
and 
enduring. Individuals with illness anxiety disorder may experience panic attacks that 
are 
triggered by their illness concerns. 


Obsessive-compulsive 
and 
related 
disorders. 
Individuals with illness anxiety disorder may have 
intrusive thoughts about 
having a disease and also may have associated compulsive behaviors 



(e.g., seeking reassurance). However, in illness anxiety disorder, the preoccupations are usually 
focused on having a disease, whereas in obsessive-compulsive disorder (OCD), the thoughts are 
intrusive and are usually focused on fears of getting a disease in the future. Most 
individuals with 
OCD have obsessions or compulsions 


360 


involving other concerns in addition to fears about 
contracting disease. In body dysmorphic 
disorder, concerns are limited to the individual s physical 
appearance, which is viewed as 
defective or flawed. 


Major depressive 
disorder. 
Some individuals with a major depressive episode ruminate about 
their 
health and worry excessively about 
illness. A separate diagnosis of illness anxiety disorder is not 
made if these concerns occur only during major depressive episodes. However, if excessive 
illness worry persists after remission of an episode of major depressive disorder, the diagnosis of 
illness anxiety disorder should be considered. 


Psychotic 
disorders. 
Individuals with illness anxiety disorder are not 
delusional 
and can 
acknowledge the possibility that 
the feared disease is not 
present. Their ideas do not 
attain the 
rigidity and intensity seen in the somatic delusions occurring in psychotic disorders (e.g., 
schizophrenia; 
delusional 
disorder, somatic type; 
major depressive disorder, with psychotic 
features). True somatic delusions are generally more bizarre (e.g., that 
an organ is rotting or 
dead) than the concerns seen in illness anxiety disorder. The concerns seen in illness anxiety 
disorder, though not founded in reality, are plausible. 


Comorbidity 


Illness anxiety disorder co-occurs with anxiety disorders (in particular, generalized anxiety 
disorder and panic disorder), OCD, and depressive disorders. Approximately two-thirds of 
individuals with illness anxiety disorder are likely to have at 
least 
one other comorbid major 
mental 
disorder. Individuals with illness anxiety disorder may have an elevated risk for 
personality disorders. 


Functional 
Neurological 
Symptom Disorder (Conversion 
Disorder) 


Diagnostic Criteria 


A. 
One 
or more 
symptoms of 
altered 
voluntary motor or sensory function. 
B. 
Clinical findings provide 
evidence 
of 
incompatibility between 
the 
symptom and 
recognized 
neurological or medical conditions. 
C. 
The 
symptom or deficit 
is not 
better explained 
by another medical or mental 
disorder. 
D. 
The 
symptom or deficit 
causes clinically significant 
distress or impairment 
in 

social, 
occupational, 
or other important 
areas of 
functioning 
or warrants medical 
evaluation. 
Coding 
note: 
The 
ICD-10-CM code 
depends on 
the 
symptom type 
(see 
below). 
Specify 
symptom type: 


F44.4 
With 
weakness 
or paralysis 
F44.4 
With 
abnormal 
movement 
(e.g., 
tremor, 
dystonia, 
myoclonus, 
gait 
disorder) 


F44.4 
With 
swallowing 
symptoms 
F44.4 
With 
speech 
symptom 
(e.g., 
dysphonia, 
slurred 
speech) 
F44.5 
With 
attacks 
or seizures 
F44.6 
With 
anesthesia 
or sensory 
loss 
F44.6 
With 
special 
sensory 
symptom 
(e.g., 
visual, 
olfactory, 
or hearing 


disturbance) 


F44.7 
With 
mixed 
symptoms 


Specify 
if: 
Acute 
episode: 
Symptoms present 
for less than 
6 
months. 
Persistent: 
Symptoms occurring 
for 6 
months or more. 


361 


Specify 
if: 
With 
psychological 
stressor 
(specify stressor) 
Without psychological 
stressor 


Diagnostic Features 


In functional 
neurological 
symptom 
disorder (conversion disorder), there may be one or more 
neurological 
symptoms of various types. Motor symptoms include weakness or paralysis; 
abnormal 
movements, such as tremor, jerks, or dystonic movements; 
and gait 
abnormalities. 
Sensory symptoms include altered, reduced, or absent 
skin sensation, vision, or hearing. 
Episodes of apparent 
unresponsiveness with or without 
limb movements may resemble epileptic 
seizures, syncope, or coma (also called dissociative, psychogenic, or nonepileptic seizures or 
attacks). Other symptoms include reduced or absent 
speech volume (dysphonia/aphonia); 
altered 
speech articulation, prosody, or fluency; 
a sensation of a lump in the throat 
(globus); 
and 
diplopia. This disorder has been called  conversion disorder  in prior editions of DSM as well 
as 
in much of the psychiatric research literature. The term 
 conversion  originated in 
psychoanalytic theory, which proposes that 
unconscious psychic conflict 
is  converted  into 
physical symptoms. 


The diagnosis rests on clinical 
findings that 
show clear evidence of incompatibility with 
recognized neurological 
disease. These should usually be elicited and interpreted in the context 
of the whole clinical 
picture by a health care professional 
with expertise in the diagnosis of 



neurological 
conditions. The diagnosis is not 
one of exclusion and can be made in individuals 
who also have neurological 
diseases like epilepsy or multiple sclerosis. The diagnosis should not 
be made simply because results from 
investigations are normal 
or because the symptom 
is 
 bizarre.  Internal 
inconsistency during examination is one way to demonstrate incompatibility 
(i.e., demonstrating that 
physical 
signs elicited through one examination method are no longer 
present 
when tested a different 
way). There are dozens of examples of such  positive  
examination findings. Examples of examination findings that 
indicate incompatibility with 
recognized neurological disease include the following: 



For 
functional 
limb weakness or 
paralysis: 
Hoover s sign, in which weakness of 
hip extension returns to normal 
strength 
with contralateral 
hip flexion against 
resistance; 
the hip abductor 
sign, in which weakness of 
thigh abduction returns to 
normal with contralateral hip abduction against resistance; or a discrepancy between on-the-bed performance (e.g., weakness 
of ankle plantar flexion) compared with another task (e.g., ability to walk on tiptoes). 
For 
functional 
tremor: 
the tremor 
entrainment 
test, in which a tremor 
changes when the individual 
is distracted by copying 
the examiner 
in making a rhythmical 
movement 
with the contralateral 
hand or 
foot. The test 
is positive when the tremor 
 entrains  the rhythm 
of 
the unaffected hand or 
foot, the tremor 
is suppressed, or 
the individual 
cannot 
copy simple 
rhythmical movements. Other features of functional limb tremor include variability in frequency or direction of the tremor. 
For 
functional 
dystonia: 
individuals typically present 
with fixed inverted position of 
the ankle, a clenched fist, or 
unilateral 
contraction of platysma, often with sudden onset. 
For 
attacks resembling epileptic seizures or 
syncope (also called functional 
or 
dissociative [nonepileptic] 
seizures): 
features 
suggestive of 
functional 
neurological 
symptom 
disorder 
include persistent 
eye closure sometimes with resistance to opening, 
bilateral 
motor 
movements with preserved awareness, or 
a duration longer 
than 5 minutes. Clinical 
features usually need to 
be combined and may be supported with a normal 
simultaneous ictal 
electroencephalogram 
(although this alone does not 
exclude all forms of epilepsy or syncope. 
362 



Forfunctional speech symptoms: internal inconsistencies in speech articulation and phonation. 
For 
functional 
visual 
symptoms: 
a tubular 
visual 
field (i.e., tunnel 
vision) 
and tests that 
indicate internal 
inconsistency in 
visual 
acuity, such as the  fogging test  (i.e., while the individual 
views the eye chart 
with both eyes open, the  good  eye is 
subtly fogged so that any useful binocular vision must be a result of  bad  eye function). 
It 
is important 
to note that 
the diagnosis of functional 
neurological 
symptom 
disorder should 
be based on the overall clinical picture and not on a single clinical finding. 


Associated Features 


Several 
associated features can support 
the diagnosis of functional 
neurological 
symptom 
disorder, although none are specific. There may be a history of other functional 
somatic 
symptoms or disorders, especially involving pain and fatigue. Onset 
may be associated with 
stress or trauma, either psychological 
or physical 
in nature. The potential 
etiological 
relevance of 
this stress or trauma may be suggested by a close temporal 
relationship. However, while 
assessment 
for stress and trauma is important, it 
may be absent 
in up to 50% of individuals, and 
the diagnosis should not be withheld if none is found. 


Functional 
neurological 
symptom 
disorder is often associated with dissociative symptoms, 



such as depersonalization, derealization, and dissociative amnesia, particularly at 
symptom 
onset 
or during attacks. 


The phenomenon of la belle indiff rence 
(i.e., lack of concern about 
the nature or 
implications of the symptom) has been associated with functional 
neurological 
symptom 
disorder, but 
it 
is not 
specific and should not 
be used to make the diagnosis. Similarly, the 
concept 
of secondary gain 
(i.e., when individuals derive external 
benefits such as money or 
release from responsibilities) is also not specific to functional neurological symptom disorder. 


Prevalence 


Transient 
functional 
neurological 
symptoms are common, but 
the precise prevalence of the 
disorder is unknown. Based on research in the United States and northern Europe, the incidence 
of individual 
persistent 
functional 
neurological 
symptoms is estimated to be 4 12/100,000 per 
year. Prevalence in specialty clinics appears to be higher, although data are limited. For example, 
5% of outpatients ages 9 17 in a Japanese psychiatric clinic and 6% of adult 
and adolescent 
admissions to an inpatient 
psychiatric hospital 
in Oman received a diagnosis consistent 
with 
functional 
neurological 
symptom 
disorder. In neurology clinics, around 5% 15% of individuals 
have a diagnosis of functional 
neurological 
symptom 
disorder in studies from 
Scotland and 
Australia. 


Development and Course 


Onset 
has been reported throughout 
the life course. The mean onset 
of nonepileptic attacks peaks 
at 
ages 20 29 years, and motor symptoms have their mean onset 
at 
ages 30 39 years. The 
symptoms can be transient 
or persistent. The prognosis may be better in younger children than in 
adolescents and adults. 


Risk and Prognostic Factors 


Temperamental. 
Maladaptive personality traits, especially emotional 
instability, are commonly 


associated with functional neurological symptom disorder. 
Environmental. 
There may be a history of childhood abuse and neglect. Stressful 
life events 
including physical injury are common but not universal triggering factors. 


363 


Genetic 
and 
physiological. 
The presence of neurological 
disease that 
causes similar symptoms is a 
risk factor (e.g., around one in five individuals with functional 
[nonepileptic] seizures also have 
epilepsy). 


Course 
modifiers. 
Short 
duration of symptoms and agreement 
with the diagnosis are positive 
prognostic factors. Maladaptive personality traits, the presence of comorbid physical 
disease, and 
the receipt of disability benefits appear to be negative prognostic factors. 


Culture-Related Diagnostic Issues 


Episodes of unresponsiveness (including seizures) and motor symptoms are the most 
common 
functional 
neurological 
symptoms across cultural 
contexts. High comorbidity between functional 



neurological 
and dissociative symptoms is common cross-culturally, especially in individuals 
with nonepileptic seizures. Changes resembling functional 
neurological 
(and dissociative) 
symptoms are common in certain culturally sanctioned rituals. If the symptoms are fully 
explained within the particular cultural 
context 
and do not 
result 
in clinically significant 
distress 
or disability, then the diagnosis of functional neurological symptom disorder is not made. 


Sex- and Gender-Related Diagnostic Issues 


Functional 
neurological 
symptom 
disorder is two to three times more common in women for 
most 
symptom 
presentations. One large clinical 
study found higher rates of cognitive impairment 
and weakness in men and increased past sexual and physical trauma in women. 


Association With Suicidal 
Thoughts or Behavior 


Cohort 
studies of functional 
neurological 
symptom 
disorder mostly show higher rates of suicidal 
thoughts and attempts. Individuals with functional 
symptoms in a neurology clinic have a higher 
rate of suicidal 
thoughts than individuals with recognized neurological 
disease. A study in 
Turkey of 100 consecutive psychiatric outpatients with functional 
neurological 
symptom 
disorder found that 
a history of suicide attempt 
was associated with risky use of alcohol, a 
history of childhood maltreatment, and greater severity of dissociative symptoms as compared 
with those who did not attempt suicide. 


Functional 
Consequences of Functional 
Neurological 
Symptom 
Disorder 


Individuals with functional 
neurological 
symptom 
disorder may have substantial 
physical 
disability. The severity of disability can be similar to that 
experienced by individuals with 
comparable recognized medical conditions. 


Differential 
Diagnosis 


Recognized 
neurological 
disease. 
The main differential 
diagnosis is recognized neurological 
disease that 
might 
better explain the symptoms. After a thorough neurological 
assessment, an 
unexpected neurological 
disease cause for the symptoms is rarely found at 
follow-up. However, 
reassessment 
may be required if the symptoms appear to be progressive. Functional 
neurological 
symptom 
disorder commonly coexists with recognized neurological 
disease and may be part 
of 
the prodromal state of some progressive neurological diseases. 


Somatic 
symptom disorder. 
Functional 
neurological 
symptom 
disorder may be diagnosed in 
addition to somatic symptom disorder. Most of the somatic symptoms 


364 


encountered in somatic symptom 
disorder cannot 
be demonstrated to be clearly incompatible 
with recognized neurological 
or medical 
disease, whereas in functional 
neurological 
symptom 
disorder, such incompatibility is required for the diagnosis. 


Factitious 
disorder and 
malingering. 
Functional 
neurological 
symptom 
disorder describes genuinely 
experienced symptoms that 
are not 
intentionally produced (i.e., not 
feigned). However, definite 



evidence of feigning (e.g., marked discrepancy between reported and observed activities of daily 
living) would suggest 
malingering if the individual s apparent 
aim 
is to obtain an obvious 
external reward, or factitious disorder in the absence of such reward. 


Dissociative 
disorders. 
Dissociative symptoms are common in individuals with functional 
neurological 
symptom 
disorder. If both functional 
neurological 
symptom 
disorder and a 
dissociative disorder are present, both diagnoses should be made. 


Body 
dysmorphic 
disorder. 
Individuals with body dysmorphic disorder are excessively concerned 
about 
a perceived defect 
in their physical 
appearance but 
do not 
complain of symptoms of 
sensory or motor functioning in the affected body part. 


Depressive 
disorders. 
In depressive disorders, individuals may report 
general 
heaviness of their 
limbs, whereas the weakness of functional 
neurological 
symptom 
disorder is more focal 
and 
prominent. Depressive disorders are also differentiated by the presence of core depressive 
symptoms. 


Panic 
disorder. 
Episodic neurological 
symptoms (e.g., tremor and paresthesia) can occur in both 
functional 
neurological 
symptom 
disorder and panic attacks. In panic attacks, the neurological 
symptoms are typically associated with characteristic cardiorespiratory symptoms and retained 
awareness. Loss of awareness with amnesia for the attack occurs in functional 
seizures but 
not 
in 
panic attacks. 


Comorbidity 


Anxiety disorders, especially panic disorder, and depressive disorders commonly co-occur with 
functional 
neurological 
symptom 
disorder. Somatic symptom 
disorder may co-occur as well. 
Personality disorders are more common in individuals with functional 
neurological 
symptom 
disorder than in the general 
population. Neurological 
or other medical 
conditions commonly 
coexist with functional neurological symptom disorder as well. 


Psychological 
Factors Affecting 
Other Medical 
Conditions 


Diagnostic Criteria 
F54 


A. 
A 
medical symptom or condition 
(other than 
a 
mental disorder) is present. 
B. 
Psychological or behavioral factors adversely affect 
the 
medical condition 
in 
one 
of 
the 
following 
ways: 
1. 
The 
factors have 
influenced 
the 
course 
of 
the 
medical condition 
as shown 
by 
a 
close 
temporal association 
between 
the 
psychological factors and 
the 
development 
or exacerbation 
of, 
or delayed 
recovery from, 
the 
medical 
condition. 
2. 
The 
factors interfere 
with 
the 
treatment 
of 
the 
medical condition 
(e.g., 
poor 
adherence). 

3. 
The 
factors constitute 
additional well-established 
health 
risks for the 
individual. 
365 


4. 
The 
factors influence 
the 
underlying 
pathophysiology, 
precipitating 
or 
exacerbating 
symptoms or necessitating 
medical attention. 
C. 
The 
psychological and 
behavioral factors in 
Criterion 
B 
are 
not 
better explained 
by another mental disorder (e.g., 
panic disorder, 
major depressive 
disorder, 
posttraumatic stress disorder). 
Specify 
current 
severity: 


Mild: 
Increases medical risk (e.g., 
inconsistent 
adherence 
with 
antihypertension 


treatment). 


Moderate: 
Aggravates underlying 
medical condition 
(e.g., 
anxiety aggravating 


asthma). 
Severe: 
Results in 
medical hospitalization 
or emergency room visit. 
Extreme: 
Results in 
severe, 
life-threatening 
risk (e.g., 
ignoring 
heart 
attack 


symptoms). 


Diagnostic Features 


The essential 
feature of psychological 
factors affecting other medical 
conditions is the presence 
of one or more clinically significant 
psychological 
or behavioral 
factors that 
adversely affect 
a 
medical 
condition by increasing the risk for suffering, death, or disability (Criterion B). These 
factors can adversely affect 
the medical 
condition by influencing its course or treatment, by 
constituting an additional 
well-established health risk factor, or by influencing the underlying 
pathophysiology to precipitate or exacerbate symptoms or to necessitate medical attention. 


Psychological 
or behavioral 
factors include psychological 
distress, patterns of interpersonal 
interaction, coping styles, and maladaptive health behaviors, such as denial 
of symptoms or poor 
adherence to medical 
recommendations. Common clinical 
examples are anxiety-exacerbating 
asthma, denial 
of need for treatment 
for acute chest 
pain, and manipulation of insulin by an 
individual 
with diabetes wishing to lose weight. Many different 
psychological 
factors have been 
demonstrated to adversely influence medical 
conditions for example, symptoms of depression 
or anxiety, stressful 
life events, relationship style, personality traits, and coping styles. The 
adverse effects can range from 
acute, with immediate medical 
consequences (e.g., Takotsubo 
cardiomyopathy), to chronic, occurring over a long period of time (e.g., chronic occupational 
stress increasing risk for hypertension). Affected medical 
conditions can be those with clear 
pathophysiology (e.g., diabetes, cancer, coronary disease), functional 
syndromes (e.g., migraine, 
irritable bowel 
syndrome, fibromyalgia), or idiopathic medical 
symptoms (e.g., pain, fatigue, 
dizziness). 


This diagnosis should be reserved for situations in which the effect 
of the psychological 
factor on the medical 
condition is evident 
and the psychological 
factor has clinically significant 
effects on the course or outcome of the medical 
condition. Abnormal 
psychological 
or behavioral 



symptoms that 
develop in response to a medical 
condition are more properly coded as an 
adjustment 
disorder (a clinically significant 
psychological 
response to an identifiable stressor). 
There must 
be reasonable evidence to suggest 
an association between the psychological 
factors 
and the medical 
condition, although it 
may often not 
be possible to demonstrate direct 
causality 
or the mechanisms underlying the relationship. 


Prevalence 


The prevalence of psychological 
factors affecting other medical 
conditions is unclear. In U.S. 
private insurance billing data, it 
was a more common diagnosis than DSM-IV somatic symptom 
disorders. 


Development and Course 


Psychological 
factors affecting other medical 
conditions can occur across the lifespan. 
Particularly with young children, corroborative history from parents or school can assist the 


366 


diagnostic evaluation. Some conditions are characteristic of particular life stages (e.g., in older 
individuals, the stress associated with acting as a caregiver for an ill spouse or partner). 


Culture-Related Diagnostic Issues 


Many differences between cultural 
contexts may influence psychological 
factors and their effects 
on medical 
conditions, such as those in language and communication style, idioms of distress, 
explanatory models of illness, patterns of seeking health care, service availability and 
organization, doctor-patient 
relationships and other healing practices, family and gender roles, 
and attitudes toward pain and death. Psychological 
factors affecting other medical 
conditions 
must 
be differentiated from 
culturally specific coping behaviors such as accessing faith, spiritual, 
or traditional 
healers or other variations in illness management 
that 
are acceptable within cultural 
contexts and represent 
an attempt 
to help heal 
the medical 
condition. These local 
practices may 
complement 
rather than obstruct 
evidence-based interventions. Use of alternative healing 
practices may delay use of medical 
services and affect 
outcomes, but 
when the intent 
of the 
healing practice is to address the problem 
in a culturally sanctioned way, these practices should 
not be pathologized as psychological factors affecting other medical conditions. 


Functional 
Consequences of Psychological 
Factors Affecting Other 
Medical 
Conditions 


Psychological 
and behavioral 
factors have been demonstrated to affect 
the course of many 
medical diseases. 


Differential 
Diagnosis 


Mental 
disorder due 
to 
another medical 
condition. 
A temporal 
association between symptoms of a 
mental 
disorder and those of a medical 
condition is also characteristic of a mental 
disorder due to 
another medical 
condition, but 
the presumed causality is in the opposite direction. In a mental 



disorder due to another medical 
condition, the medical 
condition is judged to be causing the 
mental 
disorder through a direct 
physiological 
mechanism. In psychological 
factors affecting 
other medical 
conditions, the psychological 
or behavioral 
factors are judged to affect 
the course 
of the medical condition. 


Adjustment 
disorders. 
Abnormal 
psychological 
or behavioral 
symptoms that 
develop in response 
to a medical 
condition are more properly coded as an adjustment 
disorder (a clinically significant 
psychological 
response to an identifiable stressor). For example, an individual 
with angina that 
is 
precipitated whenever he becomes enraged would be diagnosed as having psychological 
factors 
affecting other medical 
conditions, whereas an individual 
with angina who developed 
maladaptive anticipatory anxiety would be diagnosed as having an adjustment 
disorder with 
anxiety. In clinical 
practice, however, psychological 
factors and a medical 
condition are often 
mutually exacerbating (e.g., anxiety as both a precipitant 
and a consequence of angina), in which 
case the distinction is arbitrary. Other mental 
disorders frequently result 
in medical 
complications, most 
notably substance use disorders (e.g., alcohol 
use disorder, tobacco use 
disorder). If an individual 
has a coexisting major mental 
disorder that 
adversely affects or causes 
another medical 
condition, diagnoses of the mental 
disorder and the medical 
condition are 
usually sufficient. Psychological 
factors affecting other medical 
conditions is diagnosed when 
the psychological traits or behaviors do not meet criteria for a mental diagnosis. 


Somatic 
symptom disorder. 
Somatic symptom 
disorder is characterized by a combination of 
distressing somatic symptoms and excessive or maladaptive thoughts, feelings, and behavior in 
response to these symptoms or associated health concerns. The individual 
may or may not 
have a 
diagnosable medical condition. In contrast, in psychological factors 


367 


affecting other medical 
conditions, the psychological 
factors adversely affect 
a medical 
condition; 
the individual s thoughts, feelings, and behavior are not 
necessarily excessive. The 
difference is one of emphasis, rather than a clear-cut 
distinction. In psychological 
factors 
affecting other medical 
conditions, the emphasis is on the exacerbation of the medical 
condition 
(e.g., an individual 
with angina that 
is precipitated whenever he becomes anxious). In somatic 
symptom 
disorder, the emphasis is on maladaptive thoughts, feelings, and behavior (e.g., an 
individual 
with angina who worries constantly that 
she will 
have a heart 
attack, takes her blood 
pressure multiple times per day, and restricts her activities). 


Illness 
anxiety 
disorder. 
Illness anxiety disorder is characterized by high illness anxiety that 
is 
distressing and/or disruptive to daily life with minimal 
somatic symptoms. The focus of clinical 
concern is the individual s worry about 
having a disease; 
in most 
cases, no serious disease is 
present. In psychological 
factors affecting other medical 
conditions, anxiety may be a relevant 
psychological 
factor affecting a medical 
condition, but 
the clinical 
concern is the adverse effects 
on the medical condition. 


Comorbidity 


By definition, the diagnosis of psychological 
factors affecting other medical 
conditions entails a 
relevant psychological or behavioral syndrome or trait and a comorbid medical condition. 



Factitious Disorder 


Diagnostic Criteria 


F68.10FactitiousDisorder ImposedonSelf
A. 
Falsification 
of 
physical or psychological signs or symptoms, 
or induction 
of 
injury or disease, 
associated 
with 
identified 
deception. 
B. 
The 
individual presents himself 
or herself 
to 
others as ill, 
impaired, 
or injured. 
C. 
The 
deceptive 
behavior is evident 
even 
in 
the 
absence 
of 
obvious external 
rewards. 
D. 
The 
behavior is not 
better explained 
by another mental disorder, 
such 
as 
delusional disorder or another psychotic disorder. 
Specify: 


Single 
episode 
Recurrent episodes 
(two 
or more 
events of 
falsification 
of 
illness and/or 
induction 
of 
injury) 


F68.AFactitiousDisorder ImposedonAnother (PreviouslyFactitiousDisorder byProxy)
A. 
Falsification 
of 
physical or psychological signs or symptoms, 
or induction 
of 
injury or disease, 
in 
another, 
associated 
with 
identified 
deception. 
B. 
The 
individual presents another individual (victim) to 
others as ill, 
impaired, 
or 
injured. 
C. 
The 
deceptive 
behavior is evident 
even 
in 
the 
absence 
of 
obvious external 
rewards. 
D. 
The 
behavior is not 
better explained 
by another mental disorder, 
such 
as 
delusional disorder or another psychotic disorder. 
Note: 
The 
perpetrator, 
not 
the 
victim, 
receives this diagnosis. 
Specify: 


Single 
episode 
Recurrent episodes 
(two 
or more 
events of 
falsification 
of 
illness and/or 
induction 
of 
injury) 


368 


Recording Procedures 


When an individual 
falsifies illness in another (e.g., children, adults, pets), the diagnosis is 
factitious disorder imposed on another. The perpetrator, not 
the victim, is given the diagnosis. 



The victim 
may be given an abuse diagnosis (e.g., T74.12X; 
see the chapter  Other Conditions 
That May Be a Focus of Clinical Attention ). If an individual with factitious disorder imposed on 
another has also deceptively represented his or her own illness or injury, both factitious disorder 
imposed on self and on another can be diagnosed. 


Diagnostic Features 


The essential 
feature of factitious disorder is the falsification of medical 
or psychological 
signs 
and symptoms in the individual 
or others that 
are associated with the identified deception. 
Individuals with factitious disorder can also seek treatment 
for themselves or another following 
induction of injury or disease. The diagnosis requires demonstrating that 
the individual 
is taking 
surreptitious actions to misrepresent, simulate, or cause signs or symptoms of illness or injury 
even in the absence of obvious external 
rewards. The diagnosis of factitious disorder emphasizes 
the objective identification of falsification of signs and symptoms of illness and not 
the 
individual 
motivations of the falsifier. Methods of illness falsification can include exaggeration, 
fabrication, simulation, and induction. While a preexisting medical 
condition may be present, the 
deceptive behavior or induction of injury associated with deception causes others to view such 
individuals (or, in the case of factitious disorder imposed on another, the victim) as more ill 
or 
impaired, and this can lead to excessive clinical 
intervention. Individuals with factitious disorder 
might, for example, report 
feelings of depression and suicidal 
thoughts or behavior following the 
death of a spouse despite the death not 
being true or the individual s not 
having a spouse; 
deceptively report 
episodes of neurological 
symptoms (e.g., seizures, dizziness, or blacking out); 
manipulate a laboratory test 
(e.g., by adding blood to urine) to falsely indicate an abnormality; 
falsify medical 
records to indicate an illness; 
ingest 
a substance (e.g., insulin or warfarin) to 
induce an abnormal 
laboratory result 
or illness; 
or physically injure themselves or induce illness 
in themselves or another (e.g., by injecting fecal 
material 
to produce an abscess or to induce 
sepsis). Although individuals with factitious disorder most 
often present 
to health care 
professionals for treatment 
of their factitious symptoms, some individuals with factitious 
disorder choose to mislead community members in person or online about 
illness or injury 
without necessarily engaging health care professionals. 


Associated Features 


Individuals with factitious disorder imposed on self or factitious disorder imposed on another are 
at 
risk for experiencing great 
psychological 
distress or functional 
impairment 
by causing harm 
to 
themselves and others. Family, friends, faith leaders, and health care professionals are also often 
adversely affected by their behavior (e.g., devoted time, attention, and resources to provide 
medical 
care and emotional 
support 
to the falsifier). Individuals with factitious disorder imposed 
on another sometimes falsely allege the presence of educational 
deficits or disabilities in their 
children for which they demand special 
attention, often at 
considerable inconvenience to 
education professionals. 


Whereas some aspects of factitious disorders might 
represent 
criminal 
behavior (e.g., 
factitious disorder imposed on another, in which the parent s actions represent 
abuse and 
maltreatment 
of a child), such criminal 
behavior and mental 
illness are not 
mutually exclusive. 
Moreover, such behaviors, including the induction of injury or disease, are associated with 
deception. 



Prevalence 


The prevalence of factitious disorder is unknown, likely because of the role of deception in this 
population. Further complicating efforts at 
determining prevalence is the fact 
that 
health care 
professionals infrequently record the diagnosis, even in recognized cases. 


369 


Based on a study of general 
hospital 
inpatients in the United States referred for psychiatric 
consultation, it 
is estimated that 
almost 
1% have presentations that 
meet 
the criteria for factitious 
disorder. Factitious disorder imposed on self or another appears to be encountered more 
frequently in tertiary care settings than at primary care sites. 


Development and Course 


The course of factitious disorder is usually one of intermittent 
episodes. Single episodes and 
episodes that 
are characterized as persistent 
and unremitting are both less common. Onset 
is 
usually in early adulthood, often after hospitalization for a medical 
condition or a mental 
disorder. When imposed on another, the disorder may begin after hospitalization of the 
individual s child or other dependent. In individuals with recurrent 
episodes of falsification of 
signs and symptoms of illness and/or induction of injury, this pattern of successive deceptive 
contact with medical personnel, including hospitalizations, may become lifelong. 


Sex- and Gender-Related Diagnostic Issues 


While the prevalence is not 
known, a pooled analysis of all 
case series and studies finds that 
two-
thirds of individuals with factitious disorder are women and one-third are men. 


Differential 
Diagnosis 


Deception 
to 
avoid 
legal 
liability. 
Caregivers who lie about 
abuse injuries in dependents solely to 
protect 
themselves from 
liability are not 
diagnosed with factitious disorder imposed on another 
because protection from 
liability is an external 
reward (Criterion C, the deceptive behavior is 
evident 
even in the absence of obvious external 
rewards). Such caregivers who, upon 
observation, analysis of medical 
records, and/or interviews with others, are found to lie more 
extensively than needed for immediate self-protection are diagnosed with factitious disorder 
imposed on another. 


Somatic 
symptom and 
related 
disorders. 
In somatic symptom 
disorder and the care-seeking type of 
illness anxiety disorder, there may be excessive attention and treatment 
seeking for perceived 
medical 
concerns, but 
there is no evidence that 
the individual 
is providing false information or 
behaving deceptively. 


Malingering. 
Malingering is differentiated from 
factitious disorder by the intentional 
reporting of 
symptoms for personal 
gain (e.g., money, time off work). In contrast, the diagnosis of factitious 
disorder requires that 
the illness falsification is not 
fully accounted for by external 
rewards. 
Factitious disorder and malingering are not 
mutually exclusive, however. The motives in any 
single case might 
be multiple and shifting depending on the circumstances and reactions of 
others. 



Functional 
neurological 
symptom disorder (conversion 
disorder). 
Functional 
neurological 
symptom 
disorder is characterized by neurological 
symptoms that 
are inconsistent 
with neurological 


pathophysiology. Factitious disorder with neurological 
symptoms is distinguished from 
functional neurological symptom disorder by evidence of deceptive falsification of symptoms. 
Borderline 
personality 
disorder. 
Deliberate physical 
self-harm 
in the absence of suicidal 
intent 
can 


also occur in association with other mental 
disorders such as borderline personality disorder. 
Factitious disorder requires that the induction of injury occur in association with deception. 


Medical 
condition 
or mental 
disorder not 
associated 
with 
intentional 
symptom falsification. 


Presentation 
of signs and symptoms of illness that 
do not 
conform 
to an identifiable medical 
condition or 
mental 
disorder increases the likelihood of the presence of a factitious disorder. However, the 
diagnosis of factitious disorder does not exclude the 


370 


presence of a true medical 
condition or mental 
disorder, as comorbid illness often occurs in the 
individual 
along with factitious disorder. For example, individuals who might 
manipulate blood 
sugar levels to produce symptoms may also have diabetes. 


Other Specified 
Somatic Symptom and 
Related 
Disorder 


F45.8 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
somatic 


symptom and 
related 
disorder that 
cause 
clinically significant 
distress or impairment 


in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 


not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
somatic symptom and 
related 


disorders diagnostic class. 


Examples of 
presentations that 
can 
be 
specified 
using 
the 
 other specified  


designation 
include 
the 
following: 


1. 
Brief somatic 
symptom disorder: 
Duration 
of 
symptoms is less than 
6 
months. 
2. 
Brief illness 
anxiety 
disorder: 
Duration 
of 
symptoms is less than 
6 
months. 
3. 
Illness 
anxiety 
disorder without excessive 
health-related 
behaviors 
or 
maladaptive 
avoidance: 
Criterion 
D for illness anxiety disorder is not 
met. 
4. 
Pseudocyesis: 
A 
false 
belief 
of 
being 
pregnant 
that 
is associated 
with 
objective 
signs and 
reported 
symptoms of 
pregnancy. 
Unspecified 
Somatic Symptom and 
Related 
Disorder 


F45.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
somatic 



symptom and 
related 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
somatic symptom and 
related 
disorders diagnostic class. 
The 
unspecified 
somatic symptom and 
related 
disorder 
category should 
not 
be 
used 
unless there 
are 
decidedly unusual situations where 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis. 



371 



Feeding and Eating Disorders 


Feeding and eating disorders 
are characterized by a persistent 
disturbance of 
eating or eating-related behavior that 
results in the altered consumption or absorption of food and 
that 
significantly impairs physical 
health or psychosocial 
functioning. Diagnostic criteria are 
provided for pica, rumination disorder, avoidant/restrictive food intake disorder, anorexia 
nervosa, bulimia nervosa, and binge-eating disorder. 


The diagnostic criteria for anorexia nervosa, bulimia nervosa, and binge-eating disorder 
result 
in a classification scheme that 
is mutually exclusive, so that 
during a single episode, only 
one of these diagnoses can be assigned. The rationale for this approach is that, despite a number 
of common psychological 
and behavioral 
features, the disorders differ substantially in clinical 
course, outcome, and treatment needs. 


Some individuals with disorders described in this chapter report 
eating-related symptoms 
resembling those typically endorsed by individuals with substance use disorders, such as craving 
and patterns of compulsive use. This resemblance may reflect the involvement of the same neural 
systems, including those implicated in regulatory self-control 
and reward, in both groups of 
disorders. However, the relative contributions of shared and distinct 
factors in the development 
and perpetuation of eating and substance use disorders remain insufficiently understood. 


Finally, obesity is not 
included in DSM-5 as a mental 
disorder. Obesity (excess body fat) 
results from 
the long-term 
excess of energy intake relative to energy expenditure. A range of 
genetic, physiological, behavioral, and environmental 
factors that 
vary across individuals 
contributes to the development 
of obesity; 
thus, obesity is not 
considered a mental 
disorder. 
However, there are robust 
associations between obesity and a number of mental 
disorders (e.g., 
binge-eating disorder, depressive and bipolar disorders, schizophrenia). The side effects of some 
psychotropic medications contribute importantly to the development 
of obesity, and obesity may 
be a risk factor for the development of some mental disorders (e.g., depressive disorders). 


Pica 


Diagnostic Criteria 


A. 
Persistent 
eating 
of 
nonnutritive, 
nonfood 
substances over a 
period 
of 
at 
least 
1 
month. 
B. 
The 
eating 
of 
nonnutritive, 
nonfood 
substances is inappropriate 
to 
the 
developmental level of 
the 
individual. 
C. 
The 
eating 
behavior is not 
part 
of 
a 
culturally supported 
or socially normative 
practice. 

D. 
If 
the 
eating 
behavior occurs in 
the 
context 
of 
another mental disorder (e.g., 
intellectual developmental disorder [intellectual disability], 
autism spectrum 
disorder, 
schizophrenia) or medical condition 
(including 
pregnancy), 
it 
is 
sufficiently severe 
to 
warrant 
additional clinical attention. 
372 


Coding 
note: 
The 
ICD-10-CM codes for pica 
are 
F98.3 
in 
children 
and 
F50.89 
in 
adults. 


Specify 
if: 
In 
remission: 
After full criteria 
for pica 
were 
previously met, 
the 
criteria 
have 
not 
been 
met 
for a 
sustained 
period 
of 
time. 


Diagnostic Features 


The essential 
feature of pica is the eating of one or more nonnutritive, nonfood substances on a 
persistent 
basis over a period of at 
least 
1 month (Criterion A) that 
is severe enough to warrant 
clinical 
attention. Typical 
substances ingested tend to vary with age and availability and might 
include paper, soap, cloth, hair, string, wool, soil, chalk, talcum 
powder, paint, gum, metal, 
pebbles, charcoal 
or coal, ash, clay, starch, or ice. The term 
nonfood 
is included because the 
diagnosis of pica does not 
apply to ingestion of diet 
products that 
have minimal 
nutritional 
content. There is typically no aversion to food in general. The eating of nonnutritive, nonfood 
substances must 
be developmentally inappropriate (Criterion B) and not 
part 
of a culturally 
supported or socially normative practice (Criterion C). A minimum 
age of 2 years is suggested 
for a pica diagnosis to exclude developmentally normal 
mouthing of objects by infants that 
results in ingestion. The eating of nonnutritive, nonfood substances can be an associated feature 
of other mental 
disorders (e.g., intellectual 
developmental 
disorder [intellectual 
disability], 
autism 
spectrum 
disorder, schizophrenia). If the eating behavior occurs exclusively in the context 
of another mental 
disorder, a separate diagnosis of pica should be made only if the eating 
behavior is sufficiently severe to warrant additional clinical attention (Criterion D). 


Associated Features 


Although deficiencies in vitamins or minerals (e.g., zinc, iron) have been reported, often no 
specific biological 
abnormalities are found. In some cases, pica comes to clinical 
attention only 
following general 
medical 
complications (e.g., mechanical 
bowel 
problems; 
intestinal 
obstruction, such as that 
resulting from 
a bezoar; 
intestinal 
perforation; 
infections such as 
toxoplasmosis and toxocariasis as a result 
of ingesting feces or dirt; 
poisoning, such as by 
ingestion of lead-based paint). 


Prevalence 


Limited data suggest that the prevalence of pica is approximately 5% among school-age children. 
Roughly one-third of pregnant 
women, especially those with food insecurity (i.e., without 
reliable access to affordable and nutritious food), engage in pica. Conditions associated with pica 
include lack of available food and vitamin deficiency. 



Development and Course 


Onset 
of pica can occur in childhood, adolescence, or adulthood, although childhood onset 
is 
most 
commonly reported. Pica can occur in otherwise normally developing children, whereas in 
adults it 
appears more likely to occur in the context 
of intellectual 
developmental 
disorder or 
other mental 
disorders. The course of the disorder can be protracted and can result 
in medical 
emergencies (e.g., intestinal 
obstruction, acute weight 
loss, poisoning). The disorder can 
potentially be fatal depending on substances ingested. 


Risk and Prognostic Factors 


Environmental. 
Neglect, lack of supervision, and developmental 
delay can increase the risk for 
this condition. 


Culture-Related Diagnostic Issues 


In some populations, the eating of earth or other seemingly nonnutritive substances is believed to 
be of spiritual, medicinal, or other social value, or may be a culturally supported 


373 


or socially normative practice. Such behavior does not 
warrant 
a diagnosis of pica (Criterion C). 
Pica behavior may be prevalent 
in some cultural 
groups, but 
it 
should not 
be assumed to be 
socially normative without further evaluation. 


Sex- and Gender-Related Diagnostic Issues 


Pica occurs in both genders. The eating of nonnutritive, nonfood substances may manifest 
in 
pregnancy, when specific cravings (e.g., chalk or ice) may occur. The diagnosis of pica during 
pregnancy is appropriate only if such cravings lead to the ingestion of nonnutritive, nonfood 
substances to the extent 
that 
the eating of these substances poses potential 
medical 
risks. A 
worldwide meta-analysis showed the prevalence rate of pica to be 28% during pregnancy and/or 
the postpartum period. 


Diagnostic Markers 


Abdominal 
flat 
plate radiography, ultrasound, and other scanning methods may reveal 
obstructions related to pica. Blood tests and other laboratory tests can be used to ascertain levels 
of poisoning or the nature of infection. 


Functional 
Consequences of Pica 


Pica can significantly impair physical 
functioning, but 
it 
is rarely the sole cause of impairment 
in 
social 
functioning. Pica often occurs with other disorders associated with impaired social 
functioning. 


Differential 
Diagnosis 


Eating of nonnutritive, nonfood substances may occur during the course of other mental 



disorders (e.g., autism 
spectrum 
disorder, schizophrenia) and in Kleine-Levin syndrome. In any 
such instance, an additional 
diagnosis of pica should be given only if the eating behavior is 
sufficiently persistent and severe to warrant additional clinical attention. 


Anorexia 
nervosa. 
Pica can usually be distinguished from 
the other feeding and eating disorders 
by the consumption of nonnutritive, nonfood substances. It 
is important 
to note, however, that 
some presentations of anorexia nervosa include ingestion of nonnutritive, nonfood substances, 
such as paper tissues, as a means of attempting to control 
appetite. In such cases, when the eating 
of nonnutritive, nonfood substances is primarily used as a means of weight 
control, anorexia 
nervosa should be the primary diagnosis. 


Factitious 
disorder. 
Some individuals with factitious disorder may intentionally ingest 
foreign 
objects as part 
of the pattern of falsification of physical 
symptoms. In such instances, there is an 
element of deception that is consistent with deliberate induction of injury or disease. 


Nonsuicidal 
self-injury 
and 
nonsuicidal 
self-injury 
behaviors 
in 
personality 
disorders. 


Some individuals 
may swallow potentially harmful 
items (e.g., pins, needles, knives) in the context 
of maladaptive 
behavior patterns associated with personality disorders or nonsuicidal self-injury. 


Comorbidity 


Disorders most 
commonly comorbid with pica are autism 
spectrum 
disorder and intellectual 
developmental 
disorder (intellectual 
disability) and, to a lesser degree, schizophrenia and 
obsessive-compulsive disorder. Pica can be associated with trichotillomania (hair-pulling 
disorder) and excoriation (skin-picking) disorder. In comorbid presentations, the hair or skin is 
typically ingested. Pica can also be associated with avoidant/restrictive food intake disorder, 
particularly in individuals with a strong sensory component 
to their presentation. When an 
individual 
is known to have pica, assessment 
should include consideration of the possibility of 
gastrointestinal complications, poisoning, infection, and nutritional deficiency. 


374 


Rumination 
Disorder 


Diagnostic Criteria 
F98.21 


A. 
Repeated 
regurgitation 
of 
food 
over a 
period 
of 
at 
least 
1 
month. 
Regurgitated 
food 
may be 
re-chewed, 
re-swallowed, 
or spit 
out. 
B. 
The 
repeated 
regurgitation 
is not 
attributable 
to 
an 
associated 
gastrointestinal or 
other medical condition 
(e.g., 
gastroesophageal reflux, 
pyloric stenosis). 
C. 
The 
eating 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
anorexia 
nervosa, 
bulimia 
nervosa, 
binge-eating 
disorder, 
or avoidant/restrictive 
food 
intake 
disorder. 
D. 
If 
the 
symptoms occur in 
the 
context 
of 
another mental disorder (e.g., 
intellectual 
developmental disorder [intellectual disability] 
or another neurodevelopmental 

disorder), 
they are 
sufficiently severe 
to 
warrant 
additional clinical attention. 
Specify 
if: 
In 
remission: 
After full criteria 
for rumination 
disorder were 
previously met, 
the 
criteria 
have 
not 
been 
met 
for a 
sustained 
period 
of 
time. 


Diagnostic Features 


The essential 
feature of rumination disorder is the repeated regurgitation of food occurring after 
feeding or eating over a period of at 
least 
1 month (Criterion A). Previously swallowed food that 
may be partially digested is brought 
up into the mouth without 
apparent 
nausea, involuntary 
retching, or disgust. The food may be re-chewed and then ejected from 
the mouth or re-
swallowed. Regurgitation in rumination disorder should be frequent, occurring at 
least 
several 
times per week, typically daily. The behavior is not 
better explained by an associated 
gastrointestinal 
or other medical 
condition (e.g., gastroesophageal 
reflux, pyloric stenosis) 
(Criterion B) and does not 
occur exclusively during the course of anorexia nervosa, bulimia 
nervosa, binge-eating disorder, or avoidant/restrictive food intake disorder (Criterion C). If the 
symptoms occur in the context 
of another mental 
disorder (e.g., intellectual 
developmental 
disorder [intellectual 
disability]), they must 
be sufficiently severe to warrant 
additional 
clinical 
attention (Criterion D) and should represent 
a primary aspect 
of the individual s presentation 
requiring intervention. The disorder may be diagnosed across the life span, particularly in 
individuals who also have intellectual 
developmental 
disorder. Many individuals with rumination 
disorder can be directly observed engaging in the behavior by the clinician. In other instances 
diagnosis can be made on the basis of self-report 
or corroborative information from 
parents or 
caregivers. Individuals may describe the behavior as habitual or outside of their control. 


Associated Features 


Infants with rumination disorder display a characteristic position of straining and arching the 
back with the head held back, making sucking movements with their tongue. They may give the 
impression of gaining satisfaction from 
the activity. They may be irritable and hungry between 
episodes of regurgitation. Weight 
loss and failure to make expected weight 
gains are common 
features in infants with rumination disorder. Malnutrition may occur despite the infant s apparent 
hunger and the ingestion of relatively large amounts of food, particularly in severe cases, when 
regurgitation immediately follows each feeding episode and regurgitated food is expelled. 
Malnutrition might 
also occur in older children and adults, particularly when the regurgitation is 
accompanied by restriction of intake. Adolescents and adults may attempt 
to disguise the 
regurgitation behavior by placing a hand over the mouth or coughing. Some will 
avoid eating 
with others because of the acknowledged social undesirability of the 


375 


behavior. This may extend to an avoidance of eating prior to social 
situations, such as work or 
school (e.g., avoiding breakfast because it may be followed by regurgitation). 


Prevalence 



Although rumination disorder was historically described primarily among individuals with 
intellectual 
disability, the limited European data available on prevalence suggest 
that 
the disorder 
may occur in approximately 1% 2% of grade-school-age children. 


Development and Course 


Onset 
of rumination disorder can occur in infancy, childhood, adolescence, or adulthood. The 
age at 
onset 
in infants is usually between ages 3 and 12 months. In infants, the disorder 
frequently remits spontaneously, but 
its course can be protracted and can result 
in medical 
emergencies (e.g., severe malnutrition). It 
can potentially be fatal, particularly in infancy. 
Rumination disorder can have an episodic course or occur continuously until 
treated. In infants, 
as well 
as in older individuals with intellectual 
developmental 
disorder or other 
neurodevelopmental 
disorders, the regurgitation and rumination behavior appears to have a self-
soothing or self-stimulating function, similar to that 
of other repetitive motor behaviors such as 
head banging. 


Risk and Prognostic Factors 


Environmental. 
Psychosocial 
problems such as lack of stimulation, neglect, stressful 
life 
situations, and problems in the parent-child relationship may be predisposing factors in infants 
and young children. 


Functional 
Consequences of Rumination Disorder 


Malnutrition secondary to repeated regurgitation may be associated with growth delay and have 
a negative effect 
on development 
and learning potential. Some older individuals with rumination 
disorder deliberately restrict 
their food intake because of the social 
undesirability of 
regurgitation. They may therefore present 
with weight 
loss or low weight. In older children, 
adolescents, and adults, social functioning is more likely to be adversely affected. 


Differential 
Diagnosis 


Gastrointestinal 
conditions. 
It 
is important 
to differentiate regurgitation in rumination disorder 
from 
other conditions characterized by gastroesophageal 
reflux or vomiting, such as 
gastroparesis, pyloric stenosis, hiatal 
hernia, and Sandifer syndrome in infants. These other 
medical conditions can usually be ruled out on the basis of history and clinical observation. 


Anorexia 
nervosa 
and 
bulimia 
nervosa. 
Individuals with anorexia nervosa and bulimia nervosa may 
also engage in regurgitation with subsequent 
spitting out 
of food as a means of disposing of 
ingested calories because of concerns about weight gain. 


Comorbidity 


Regurgitation with associated rumination can occur in the context 
of a concurrent 
medical 
condition or another mental 
disorder (e.g., generalized anxiety disorder). When the regurgitation 
occurs in this context, a diagnosis of rumination disorder is appropriate only when the severity of 
the disturbance exceeds that 
routinely associated with such conditions or disorders and warrants 
additional clinical attention. 



376 


Avoidant/Restrictive Food 
Intake Disorder 


Diagnostic Criteria 
F50.82 


A. 
An 
eating 
or feeding 
disturbance 
(e.g., 
apparent 
lack of 
interest 
in 
eating 
or food; 
avoidance 
based 
on 
the 
sensory characteristics of 
food; 
concern 
about 
aversive 
consequences of 
eating) associated 
with 
one 
(or more) of 
the 
following: 
1. 
Significant 
weight 
loss (or failure 
to 
achieve 
expected 
weight 
gain 
or faltering 
growth 
in 
children). 
2. 
Significant 
nutritional deficiency. 
3. 
Dependence 
on 
enteral feeding 
or oral nutritional supplements. 
4. 
Marked 
interference 
with 
psychosocial functioning. 
B. 
The 
disturbance 
is not 
better explained 
by lack of 
available 
food 
or by an 
associated 
culturally sanctioned 
practice. 
C. 
The 
eating 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
anorexia 
nervosa 
or bulimia 
nervosa, 
and 
there 
is no 
evidence 
of 
a 
disturbance 
in 
the 
way 
in 
which 
one s body weight 
or shape 
is experienced. 
D. 
The 
eating 
disturbance 
is not 
attributable 
to 
a 
concurrent 
medical condition 
or 
not 
better explained 
by another mental disorder. 
When 
the 
eating 
disturbance 
occurs in 
the 
context 
of 
another condition 
or disorder, 
the 
severity of 
the 
eating 
disturbance 
exceeds that 
routinely associated 
with 
the 
condition 
or disorder and 
warrants additional clinical attention. 
Specify 
if: 
In 
remission: 
After full criteria 
for avoidant/restrictive 
food 
intake 
disorder were 
previously met, 
the 
criteria 
have 
not 
been 
met 
for a 
sustained 
period 
of 
time. 


Diagnostic Features 


Avoidant/restrictive food intake disorder replaces and extends the DSM-IV diagnosis of feeding 
disorder of infancy or early childhood to include older children, adolescents, and adults. The 
main diagnostic feature of avoidant/restrictive food intake disorder is avoidance or restriction of 
food intake that 
is associated with one or more of the following consequences: 
significant 
weight 
loss, significant 
nutritional 
deficiency (or related health impact), dependence on enteral 
feeding 
or oral 
nutritional 
supplements, or marked interference with psychosocial 
functioning (Criterion 
A). 


In some individuals, food avoidance or restriction is based on the sensory characteristics of 
qualities of food, such as extreme sensitivity to appearance, color, smell, texture, temperature, or 
taste. Such behavior has been described as  restrictive eating,   selective eating,   choosy 
eating,   perseverant 
eating,   chronic food refusal,  and  food neophobia  and may manifest 
as 



refusal 
to eat 
particular brands of foods or to tolerate the smell 
of food being eaten by others. 
Individuals with heightened sensory sensitivities associated with autism 
may show similar 
behaviors. 


In other individuals, food avoidance or restriction represents a conditioned negative response 
associated with food intake following, or in anticipation of, an aversive experience, such as 
choking; 
a traumatic procedure, usually involving the gastrointestinal 
tract 
(e.g., 
esophagoscopy); 
or repeated vomiting. The terms functional 
dysphagia 
and globus hystericus 
have also been used for such conditions. 


In yet 
other individuals, food avoidance or restriction manifests as a lack of interest 
in eating 
or food. 


The determination of whether weight 
loss is significant 
(Criterion A1) is a clinical 
judgment; 
instead of losing weight, children and adolescents who have not 
completed growth may not 
maintain weight or height increases along their developmental trajectory. 


377 


Determination of significant 
nutritional 
deficiency (Criterion A2) is also based on clinical 
assessment 
(e.g., assessment 
of dietary intake, physical 
examination, and laboratory testing), and 
related impact 
on physical 
health can be of a similar severity to that 
seen in anorexia nervosa 
(e.g., hypothermia, bradycardia, anemia). In severe cases, particularly in infants, malnutrition can 
be life-threatening.  Dependence  on enteral 
feeding or oral 
nutritional 
supplements (Criterion 
A3) means that 
supplementary feeding is required to sustain adequate intake. Examples of 
individuals requiring supplementary feeding include infants with failure to thrive who require 
nasogastric tube feeding, children with neurodevelopmental 
disorders who are dependent 
on 
nutritionally complete supplements, and individuals who rely on gastrostomy tube feeding or 
complete oral 
nutrition supplements in the absence of an underlying medical 
condition. Inability 
to participate in normal 
social 
activities, such as eating with others, attending school 
or work, or 
sustaining relationships as a result 
of the disturbance would indicate marked interference with 
psychosocial 
functioning (Criterion A4). Substantial 
disruption of family functioning (e.g., 
marked restriction of foods permitted in the home, inordinate accommodations to provide foods 
from specific grocery stores or restaurants) may also satisfy Criterion A4. 


Avoidant/restrictive food intake disorder does not 
include avoidance or restriction of food 
intake related to lack of availability of food (e.g., food insecurity) or to cultural 
practices (e.g., 
religious fasting or normal 
dieting) (Criterion B). The disturbance is not 
better explained by 
excessive concern about 
body weight 
or shape (Criterion C) or by concurrent 
medical 
factors or 
mental disorders (Criterion D). 


Associated Features 


Several 
features may be associated with food avoidance or reduced food intake, and these 
features may differ across ages. Very young infants may present 
with food refusal, gagging, or 
vomiting. Infants and young children may not 
engage with a primary caregiver during feeding or 
communicate hunger in favor of other activities. In older children and adolescents, food 
avoidance or restriction may be associated with more generalized emotional 
difficulties that 
do 
not 
meet 
diagnostic criteria for an anxiety, depressive, or bipolar disorder, sometimes called 



 food avoidance emotional disorder.  


Prevalence 


Little information is available on the prevalence of avoidant/restrictive food intake disorder. A 
study in Australia reported a frequency of 0.3% among individuals age 15 years or older. 


Development and Course 


Food avoidance or restriction associated with insufficient 
intake or lack of interest 
in eating most 
commonly develops in infancy or early childhood and may persist 
in adulthood. Likewise, 
avoidance based on sensory characteristics of food tends to arise in the first 
decade of life but 
may persist 
into adulthood. Avoidance related to aversive consequences can arise at 
any age. The 
scant 
literature regarding long-term 
outcomes suggests that 
food avoidance or restriction based 
on sensory aspects is relatively stable and long-standing, but 
when persisting into adulthood, 
such avoidance/restriction can be associated with relatively normal 
functioning. There is 
currently insufficient 
evidence directly linking avoidant/restrictive food intake disorder and 
subsequent onset of an eating disorder. 


Infants with avoidant/restrictive food intake disorder may be irritable and difficult 
to console 
during feeding, or may appear apathetic and withdrawn. In some instances, caregiver-child 
interaction may contribute to the infant s feeding problem 
(e.g., presenting food inappropriately, 
or interpreting the infant s behavior as an act 
of aggression or rejection). Inadequate nutritional 
intake may exacerbate the associated features (e.g., irritability, developmental 
lags) and further 
contribute to feeding difficulties. Associated factors 


378 


include infant 
temperament 
or developmental 
impairments that 
reduce an infant s 
responsiveness to feeding. Coexisting parental 
psychopathology, or child abuse or neglect, is 
suggested if feeding and weight 
improve in response to changing caregivers. In infants, children, 
and prepubertal 
adolescents, avoidant/restrictive food intake disorder may be associated with 
growth delay, and the resulting malnutrition negatively affects development 
and learning 
potential. In older children, adolescents, and adults, social 
functioning tends to be adversely 
affected. Regardless of the age, family function may be affected, with heightened stress at 
mealtimes and in other feeding or eating contexts involving friends and relatives. 


Avoidant/restrictive food intake disorder manifests more commonly in children and 
adolescents than in adults, and there may be a long delay between onset 
and clinical 
presentation. 
Triggers for presentation vary considerably and include physical, social, and emotional 
difficulties. 


Risk and Prognostic Factors 


Temperamental. 
Anxiety disorders, autism spectrum disorder, obsessive-compulsive disorder, and 
attention-deficit/hyperactivity disorder may increase risk for avoidant 
or restrictive feeding or 
eating behavior characteristic of the disorder. 


Environmental. 
Environmental 
risk factors for avoidant/restrictive food intake disorder include 
familial 
anxiety. Higher rates of feeding disturbances may occur in children of mothers with 



eating disorders. 
Genetic 
and 
physiological. 
History of gastrointestinal 
conditions, gastroesophageal 
reflux disease, 
vomiting, and a range of other medical 
problems has been associated with feeding and eating 
behaviors characteristic of avoidant/restrictive food intake disorder. 


Culture-Related Diagnostic Issues 


Presentations similar to avoidant/restrictive food intake disorder occur in various populations, 
including in the United States, Canada, Australia, Europe, Japan, and China. Avoidant/restrictive 
food intake disorder should not 
be diagnosed when avoidance of food intake is solely related to 
specific religious or cultural practices. 


Sex- and Gender-Related Diagnostic Issues 


Avoidant/restrictive food intake disorder appears to be approximately equally common in boys 
and girls, but 
avoidant/restrictive food intake disorder comorbid with autism 
spectrum 
disorder 
has a male predominance. Food avoidance or restriction related to altered sensory sensitivities 
can occur in some physiological 
conditions, most 
notably pregnancy, but 
is not 
usually extreme 
and does not meet full criteria for the disorder. 


Functional 
Consequences of Avoidant/Restrictive Food Intake Disorder 


Associated developmental 
and functional 
limitations include impairment 
of physical 
development 
and social 
difficulties that 
can have a significant 
negative impact 
on family 
function. 


Differential 
Diagnosis 


Restriction of food intake is a nonspecific symptom 
that 
can accompany a number of mental 
disorders and medical 
conditions and that 
can also be developmentally appropriate. 
Avoidant/restrictive food intake disorder can be diagnosed concurrently with the disorders below 
if all criteria are met, and the eating disturbance requires specific clinical attention. 


379 


Other medical 
conditions 
(e.g., 
gastrointestinal 
disease, 
food 
allergies 
and 
intolerances, 
occult 
malignancies).

Restriction of food intake may occur in other medical 
conditions, especially those with ongoing 
symptoms such as vomiting, loss of appetite, nausea, abdominal 
pain, or diarrhea. A diagnosis of 
avoidant/restrictive food intake disorder requires that 
the disturbance of intake is beyond that 
directly accounted for by physical 
symptoms consistent 
with a medical 
condition; 
the eating 
disturbance may also persist 
after being triggered by a medical 
condition and following 
resolution of the medical condition. 


Underlying medical 
or comorbid mental 
conditions may complicate feeding and eating. 
Because older individuals, postsurgical 
patients, and individuals receiving chemotherapy often 
lose their appetite, an additional 
diagnosis of avoidant/restrictive food intake disorder requires 
that the eating disturbance is a primary focus for intervention. 
Obsessive-compulsive 
and 
related 
disorder due 
to 
pediatric 
acute-onset 
neuropsychiatric 



syndrome.

Acute-onset 
symptoms, late age at 
onset, or atypical 
symptoms suggest 
the need for a thorough 
assessment 
to rule out 
the diagnosis of obsessive-compulsive and related disorder due to 
pediatric acute-onset 
neuropsychiatric syndrome (PANS). PANS 
is characterized by abrupt, 
dramatic onset 
of obsessive-compulsive symptoms or severely restricted food intake, together 
with a range of additional neuropsychiatric symptoms. 


Specific 
neurological/neuromuscular, 
structural, 
or congenital 
disorders 
and 
conditions 
associated 
with 
feeding 
difficulties. 


Feeding difficulties are common in a number of congenital 
and neurological 
conditions often 
related to problems with oral/esophageal/pharyngeal 
structure and function, such as hypotonia of 
musculature, tongue protrusion, and unsafe swallowing. Avoidant/restrictive food intake disorder 
can be diagnosed in individuals with such presentations as long as all diagnostic criteria are met. 


Reactive 
attachment 
disorder. 
Some degree of withdrawal 
from 
caregivers is characteristic of 
reactive attachment 
disorder and can lead to a disturbance in the caregiver-child relationship that 
can affect 
feeding and the child s intake. Avoidant/restrictive food intake disorder should be 
diagnosed concurrently only if all 
criteria are met 
for both disorders and the feeding disturbance 
is a primary focus for intervention. 


Autism spectrum disorder. 
Individuals with autism 
spectrum 
disorder often present 
with rigid 
eating behaviors and heightened sensory sensitivities. However, these features do not 
always 
result 
in the level 
of impairment 
that 
would be required for a diagnosis of avoidant/restrictive 
food intake disorder. Avoidant/restrictive food intake disorder should be diagnosed concurrently 
only if all 
criteria are met 
for both disorders and when the eating disturbance requires specific 
treatment. 
Specific 
phobia, 
social 
anxiety 
disorder, 
and 
other anxiety 
disorders. 
Specific phobia, other type, 


includes as an example  situations that 
may lead to choking or vomiting  and can represent 
the 
primary trigger for the fear, anxiety, or avoidance required for diagnosis. Distinguishing specific 
phobia from 
avoidant/restrictive food intake disorder can be difficult 
when a fear of choking or 
vomiting has resulted in food avoidance. Although avoidance or restriction of food intake 
secondary to a pronounced fear of choking or vomiting can be conceptualized as specific phobia, 
in situations when the eating problem 
becomes the primary focus of clinical 
attention, 
avoidant/restrictive food intake disorder becomes the appropriate diagnosis. In social 
anxiety 
disorder, the individual 
may present 
with a fear of being observed by others while eating, which 
can also occur in avoidant/restrictive food intake disorder. 


Anorexia 
nervosa. 
Restriction of energy intake relative to requirements leading to significantly 
low body weight 
is a core feature of anorexia nervosa. However, individuals with anorexia 
nervosa also display a fear of gaining weight 
or of becoming fat, or persistent 
behavior that 
interferes with weight gain, as well as specific disturbances in 


380 


relation to perception and experience of their own body weight 
and shape. These features are not 
present 
in avoidant/restrictive food intake disorder, and the two disorders should not 
be 
diagnosed concurrently. Differential 
diagnosis between avoidant/restrictive food intake disorder 
and anorexia nervosa may be difficult, especially in late childhood and early adolescence, 
because these disorders may share a number of common symptoms (e.g., food avoidance, low 



weight). Differential 
diagnosis is also potentially difficult 
in individuals with anorexia nervosa 
who deny any fear of fatness but 
nonetheless engage in persistent 
behaviors that 
prevent 
weight 
gain and who do not 
recognize the medical 
seriousness of their low weight a presentation 
sometimes termed  non fat 
phobic anorexia nervosa.  Full 
consideration of symptoms, course, 
and family history is advised, and diagnosis may be best 
made in the context 
of a clinical 
relationship over time. In some individuals, avoidant/restrictive food intake disorder might 
precede the onset of anorexia nervosa. 


Obsessive-compulsive 
disorder. 
Individuals with obsessive-compulsive disorder may present 
with 
avoidance or restriction of intake in relation to preoccupations with food or ritualized eating 
behavior. Avoidant/restrictive food intake disorder should be diagnosed concurrently only if all 
criteria are met 
for both disorders and when the aberrant 
eating is a major aspect 
of the clinical 
presentation requiring specific intervention. 


Major depressive 
disorder. 
In major depressive disorder, appetite might 
be affected to such an 
extent 
that 
individuals present 
with significantly restricted food intake, usually in relation to 
overall 
energy intake and often associated with weight 
loss. Usually appetite loss and related 
reduction of intake abate with resolution of mood problems. Avoidant/restrictive food intake 
disorder should only be used concurrently if full 
criteria are met 
for both disorders and when the 
eating disturbance requires specific treatment. 


Schizophrenia 
spectrum disorders. 
Individuals with schizophrenia, delusional 
disorder, or other 
psychotic disorders may exhibit 
odd eating behaviors, avoidance of specific foods because of 
delusional 
beliefs, or other manifestations of avoidant 
or restrictive intake. In some cases, 
delusional 
beliefs may contribute to a concern about 
negative consequences of ingesting certain 
foods. Avoidant/restrictive food intake disorder should be used concurrently only if all 
criteria 
are met for both disorders and when the eating disturbance requires specific treatment. 
Factitious 
disorder or factitious 
disorder imposed 
on 
another. 
Avoidant/restrictive food intake 


disorder should be differentiated from 
factitious disorder or factitious disorder imposed on 
another. In order to assume the sick role, some individuals with factitious disorder may 
intentionally describe diets that 
are much more restrictive than those they are actually able to 
consume, as well 
as complications of such behavior, such as a need for enteral 
feedings or 
nutritional 
supplements, an inability to tolerate a normal 
range of foods, and/or an inability to 
participate normally in age-appropriate situations involving food. The presentation may be 
impressively dramatic and engaging, and the symptoms reported inconsistently. In factitious 
disorder imposed on another, the caregiver describes symptoms consistent 
with 
avoidant/restrictive food intake disorder and may induce physical 
symptoms such as failure to 
gain weight. As with any diagnosis of factitious disorder imposed on another, the caregiver 
receives the diagnosis rather than the affected individual, and diagnosis should be made only on 
the basis of a careful, comprehensive assessment 
of the affected individual, the caregiver, and 
their interaction. 


Developmentally 
normal 
behavior. 
During normal 
development, some toddlers and children 
transiently narrow the variety of foods they are willing to eat. This phenomenon, sometimes 
referred to as  picky eating,  usually resolves spontaneously without 
intervention. 
Avoidant/restrictive food intake disorder does not 
include such developmentally normal 
behaviors unless they become sufficiently severe to lead to failure to meet 
appropriate nutritional 



needs or produce significant impairment in functioning (Criterion A). 


381 


Comorbidity 


The most 
commonly observed disorders comorbid with avoidant/restrictive food intake disorder 
are anxiety disorders, obsessive-compulsive disorder, and neurodevelopmental 
disorders 
(specifically autism 
spectrum 
disorder, attention-deficit/hyperactivity disorder, and intellectual 
developmental disorder [intellectual disability]). 


Anorexia Nervosa 


Diagnostic Criteria 


A. 
Restriction 
of 
energy intake 
relative 
to 
requirements, 
leading 
to 
a 
significantly low 
body weight 
in 
the 
context 
of 
age, 
sex, 
developmental trajectory, 
and 
physical 
health. 
Significantly low weight 
is defined 
as a 
weight 
that 
is less than 
minimally 
normal or, 
for children 
and 
adolescents, 
less than 
that 
minimally expected. 
B. 
Intense 
fear of 
gaining 
weight 
or of 
becoming 
fat, 
or persistent 
behavior that 
interferes with 
weight 
gain, 
even 
though 
at 
a 
significantly low weight. 
C. 
Disturbance 
in 
the 
way in 
which 
one s body weight 
or shape 
is experienced, 
undue 
influence 
of 
body weight 
or shape 
on 
self-evaluation, 
or persistent 
lack of 
recognition 
of 
the 
seriousness of 
the 
current 
low body weight. 
Coding 
note: 
The 
ICD-10-CM code 
depends on 
the 
subtype 
(see 
below). 


Specify 
whether: 
F50.01 
Restricting 
type: 
During 
the 
last 
3 
months, 
the 
individual has not 
engaged 
in 
recurrent 
episodes of 
binge-eating 
or purging 
behavior (i.e., 
self-
induced 
vomiting 
or the 
misuse 
of 
laxatives, 
diuretics, 
or enemas). 
This subtype 


describes presentations in 
which 
weight 
loss is accomplished 
primarily through 
dieting, 
fasting, 
and/or excessive 
exercise. 
F50.02 
Binge-eating/purging 
type: 
During 
the 
last 
3 
months, 
the 
individual has 


engaged 
in 
recurrent 
episodes of 
binge-eating 
or purging 
behavior (i.e., 
self-
induced 
vomiting 
or the 
misuse 
of 
laxatives, 
diuretics, 
or enemas). 


Specify 
if: 
In 
partial 
remission: 
After full criteria 
for anorexia 
nervosa 
were 
previously met, 
Criterion 
A 
(low body weight) has not 
been 
met 
for a 
sustained 
period, 
but 
either 
Criterion 
B 
(intense 
fear of 
gaining 
weight 
or becoming 
fat 
or behavior that 
interferes with 
weight 
gain) or Criterion 
C (disturbances in 
self-perception 
of 
weight 
and 
shape) is still met. 


In 
full 
remission: 
After full criteria 
for anorexia 
nervosa 
were 
previously met, 
none 
of 
the 
criteria 
have 
been 
met 
for a 
sustained 
period 
of 
time. 



Specify 
current 
severity: 
The 
minimum level of 
severity is based, 
for adults, 
on 
current 
body mass index (BMI) 
(see 
below) or, 
for children 
and 
adolescents, 
on 
BMI 
percentile. 
The 
ranges below 
are 
derived 
from World 
Health 
Organization 
categories for thinness in 
adults; 
for 
children 
and 
adolescents, 
corresponding 
BMI 
percentiles should 
be 
used. 
The 
level 
of 
severity may be 
increased 
to 
reflect 
clinical symptoms, 
the 
degree 
of 
functional 
disability, 
and 
the 
need 
for supervision. 


Mild: 
BMI = 17 
kg/m2. 


Moderate: 
BMI 
16 16.99 
kg/m2. 


Severe: 
BMI 
15 15.99 
kg/m2. 


Extreme: 
BMI < 15 
kg/m2. 


382 


Subtypes 


Most 
individuals with the binge-eating/purging type of anorexia nervosa who binge eat 
also 
purge through self-induced vomiting or the misuse of laxatives, diuretics, or enemas. Some 
individuals with this subtype of anorexia nervosa do not 
binge eat 
but 
do regularly purge after 
the consumption of small amounts of food. 


Crossover between the subtypes over the course of the disorder is not 
uncommon; 
therefore, 
subtype description should be used to describe current symptoms rather than longitudinal course. 


Diagnostic Features 


There are three essential features of anorexia nervosa: persistent energy intake restriction; intense 
fear of gaining weight 
or of becoming fat, or persistent 
behavior 
that 
interferes with weight 
gain; 
and a disturbance in self-perceived weight 
or shape. The individual 
maintains a body weight 
that 
is below a minimally normal 
level 
for age, sex, developmental 
trajectory, and physical 
health 
(Criterion A). Individuals  body weights frequently meet 
this criterion following a significant 
weight 
loss, but 
among children and adolescents, there may alternatively be failure to make 
expected weight 
gain or to maintain a normal 
developmental 
trajectory (i.e., while growing in 
height) instead of weight loss. 


Criterion A requires that 
the individual s weight 
be significantly low (i.e., less than 
minimally normal 
or, for children and adolescents, less than that 
minimally expected). Weight 
assessment 
can be challenging because normal 
weight 
range differs among individuals, and 
different 
thresholds have been published defining thinness or underweight 
status. Body mass 
index (BMI; 
calculated as weight 
in kilograms/height 
in meters2) is a useful 
measure to assess 
body weight 
for height. For adults, a BMI of 18.5 kg/m2 
has been employed by the Centers for 
Disease Control 
and Prevention (CDC) and the World Health Organization (WHO) as the lower 
limit 
of normal 
body weight. Therefore, most 
adults with a BMI greater than or equal 
to 18.5 
kg/m2 
would not 
be considered to have a significantly low body weight. On the other hand, a 
BMI of lower than 17.0 kg/m2 
has been considered by the WHO to indicate moderate or severe 
thinness; 
therefore, an individual 
with a BMI less than 17.0 kg/m2 
would likely be considered to 



have a significantly low weight. An adult 
with a BMI between 17.0 and 18.5 kg/m2, or even 
slightly above 18.5 kg/m2, might 
be considered to have a significantly low weight 
if clinical 
history or other physiological 
information supports this judgment. Adults who are not 
underweight 
by population-based standards for example, adults with BMIs of 19.0 kg/m2 
or 
greater should not 
be assigned a diagnosis of anorexia nervosa; 
a diagnosis of other specified 
feeding or eating disorder (atypical anorexia nervosa) may be considered for such individuals. 


For children and adolescents, determining a BMI-for-age percentile is useful 
(see, e.g., the 
CDC 
BMI percentile calculator for children and teenagers; 
https://www.cdc.gov/healthyweight/bmi/calculator.html). As for adults, it 
is not 
possible to 
provide definitive standards for judging whether a child s or an adolescent s weight 
is 
significantly low, and variations in developmental 
trajectories among youth limit 
the utility of 
simple numerical 
guidelines. The CDC 
has used a BMI-for-age below the 5th percentile as 
suggesting underweight; 
children and adolescents with a BMI above this benchmark may be 
judged to be significantly underweight 
in light 
of failure to maintain their expected growth 
trajectory. However, such individuals whose BMI nonetheless remains greater than the median 
BMI for age should not 
be assigned a diagnosis of anorexia nervosa; 
a diagnosis of other 
specified feeding or eating disorder (atypical 
anorexia nervosa) may be considered for such 
individuals. 


Individuals with this disorder typically display an intense fear of gaining weight 
or of 
becoming fat 
(Criterion B). This intense fear of becoming fat 
is usually not 
alleviated by weight 
loss. In fact, concern about 
weight 
gain may increase even as weight 
falls. Younger individuals 
with anorexia nervosa, as well as some adults, may not recognize or 


383 


acknowledge a fear of weight 
gain. In the absence of another explanation for the significantly 
low weight, clinician inference drawn from 
collateral 
history, observational 
data, physical 
and 
laboratory findings, or longitudinal 
course either indicating a fear of weight 
gain or supporting 
persistent behaviors that prevent it may be used to establish Criterion B. 


The experience and significance of body weight 
and shape are distorted in these individuals 
(Criterion C). Some individuals feel 
globally overweight. Others realize that 
they are thin but 
are 
still 
concerned that 
certain body parts, particularly the abdomen, buttocks, and thighs, are  too 
fat.  They may employ a variety of techniques to evaluate their body size or weight, including 
frequent 
weighing, obsessive measuring of body parts, and persistent 
use of a mirror to check for 
perceived areas of  fat.  The self-esteem 
of individuals with anorexia nervosa is highly 
dependent 
on their perceptions of body shape and weight. Weight 
loss is often viewed as an 
impressive achievement 
and a sign of extraordinary self-discipline, whereas weight 
gain is 
perceived as an unacceptable failure of self-control. Although some individuals with this 
disorder may acknowledge being thin, they often do not 
recognize the serious medical 
implications of their malnourished state. 


Often, the individual 
is brought 
to professional 
attention by family members after marked 
weight 
loss (or failure to make expected weight 
gains) has occurred. If individuals seek help on 
their own, it 
is usually because of distress over the somatic and psychological 
sequelae of 
starvation. It 
is rare for an individual 
with anorexia nervosa to complain of weight 
loss per se. In 
fact, individuals with anorexia nervosa frequently either lack insight 
into or deny the problem. It 



is therefore often important 
to obtain information from 
family members or other sources to 
evaluate the history of weight loss and other features of the illness. 


Associated Features 


The semistarvation of anorexia nervosa, and the purging behaviors sometimes associated with it, 
can result 
in significant 
and potentially life-threatening medical 
conditions. The nutritional 
compromise associated with this disorder affects most 
major organ systems and can produce a 
variety of disturbances. Physiological 
disturbances, including amenorrhea and vital 
sign 
abnormalities, are common. While most 
of the physiological 
disturbances associated with 
malnutrition are reversible with nutritional 
rehabilitation, some, including loss of bone mineral 
density, are often not 
completely reversible. Behaviors such as self-induced vomiting and misuse 
of laxatives, diuretics, and enemas may cause a number of disturbances that 
lead to abnormal 
laboratory findings; 
however, some individuals with anorexia nervosa exhibit 
no laboratory 
abnormalities. 


When seriously underweight, many individuals with anorexia nervosa have depressive signs 
and symptoms such as depressed mood, social 
withdrawal, irritability, insomnia, and diminished 
interest 
in sex. Because these features are also observed in individuals without 
anorexia nervosa 
who are significantly undernourished, many of the depressive features may be secondary to the 
physiological 
sequelae of semistarvation, although they may also be sufficiently severe to 
warrant an additional diagnosis of major depressive disorder. 


Obsessive-compulsive features, both related and unrelated to food, are often prominent. Most 
individuals with anorexia nervosa are preoccupied with thoughts of food. Some collect 
recipes or 
hoard food. Observations of behaviors associated with other forms of starvation suggest 
that 
obsessions and compulsions related to food may be exacerbated by undernutrition. When 
individuals with anorexia nervosa exhibit 
obsessions and compulsions that 
are not 
related to 
food, body shape, or weight, an additional 
diagnosis of obsessive-compulsive disorder (OCD) 
may be warranted. 


Other features sometimes associated with anorexia nervosa include concerns about 
eating in 
public, feelings of ineffectiveness, a strong desire to control 
one s environment, inflexible 
thinking, limited social spontaneity, and overly restrained emotional expression. 


384 


Compared with individuals with anorexia nervosa, restricting type, those with binge-
eating/purging type have higher rates of impulsivity and are more likely to abuse alcohol 
and 
other drugs. 


Some individuals with anorexia nervosa show excessive levels of physical 
activity. Increases 
in physical 
activity often precede onset 
of the disorder, and over the course of the disorder 
increased activity accelerates weight 
loss. During treatment, excessive activity may be difficult 
to control, thereby jeopardizing weight recovery. 


Individuals with anorexia nervosa may misuse medications, such as by manipulating dosage, 
in order to achieve weight 
loss or avoid weight 
gain. Individuals with diabetes mellitus may omit 
or reduce insulin doses in order to minimize carbohydrate utilization. 



Prevalence 


According to two U.S. epidemiological 
studies conducted in community samples, the 12-month 
prevalence of anorexia nervosa ranges from 
0.0% to 0.05% with much higher rates in women 
than in men (0% to 0.08% in women; 
0% to 0.01% in men), and the lifetime prevalence ranges 
from 
0.60% to 0.80% (0.9% to 1.42% in women; 
0.12% to 0.3% in men). By contrast, one study 
of adolescents found similar rates in both genders. 


Anorexia nervosa appears to be most 
prevalent 
in postindustrialized, high-income countries 
such as in the United States, many European countries, Australia, New Zealand, and Japan. 
Although the prevalence of anorexia nervosa is uncertain in most 
low- and middle-income 
countries, it 
appears to be increasing in many countries in the Global 
South, including in Asia 
and the Middle East. Anorexia nervosa occurs across U.S. ethnoracial 
groups; 
however, its 
prevalence seems to be lower among Latinx and non-Latinx Black Americans than among non-
Latinx Whites. 


Development and Course 


Anorexia nervosa commonly begins during adolescence or young adulthood. It 
rarely begins 
before puberty or after age 40, but 
cases of both early and late onset 
have been described. The 
onset 
of this disorder is often associated with a stressful 
life event, such as leaving home for 
college. The course and outcome of anorexia nervosa are highly variable. Younger individuals 
may manifest 
atypical 
features, including denying  fear of fat.  Older individuals more likely 
have a longer duration of illness, and their clinical 
presentation may include more signs and 
symptoms of long-standing disorder. Clinicians should not 
exclude anorexia nervosa from 
the 
differential diagnosis solely on the basis of older age. 


Many individuals have a period of changed eating behavior prior to full 
criteria for the 
disorder being met. Some individuals with anorexia nervosa recover fully after a single episode, 
with some exhibiting a fluctuating pattern of weight 
gain followed by relapse, and others 
experiencing a chronic course over many years. Hospitalization may be required to restore 
weight 
and to address medical 
complications. Most 
individuals with anorexia nervosa experience 
remission within 5 years of presentation. Among individuals admitted to hospitals, overall 
remission rates may be lower. The crude mortality rate for anorexia nervosa is approximately 5% 
per decade. Death most 
commonly results from 
medical 
complications associated with the 
disorder itself or from suicide. 


Risk and Prognostic Factors 


Temperamental. 
Individuals who develop anxiety disorders or display obsessional 
traits in 


childhood are at increased risk for developing anorexia nervosa. 
Environmental. 
Historical 
and cross-cultural 
variability in the prevalence of anorexia nervosa 
supports its association with cultures and settings in which thinness is valued. Occupations and 
avocations that 
encourage thinness, such as modeling and elite athletics, are also associated with 
increased risk. 


385 



Genetic 
and 
physiological. 
There is an increased risk for anorexia nervosa and for other eating and 
psychiatric disorders among biological 
relatives of individuals with anorexia nervosa. Genome-
wide association studies have begun to identify specific risk loci, including loci 
associated with 
other psychiatric disorders and with metabolic traits such as insulin resistance and lipid profile. 
A range of brain abnormalities, many suggesting abnormal 
processing of reward, has been 
described in anorexia nervosa using functional 
imaging technologies such as functional 
magnetic 
resonance imaging and positron emission tomography. The degree to which these findings reflect 
changes associated with malnutrition versus primary abnormalities associated with the disorder 
is unclear. 


Culture-Related Diagnostic Issues 


Anorexia nervosa occurs across culturally and socially diverse populations, although available 
evidence suggests cross-cultural 
variation in its occurrence and presentation. The presentation of 
weight 
concerns among individuals with feeding and eating disorders varies substantially across 
cultural 
contexts. The absence of an expressed intense fear of weight 
gain, sometimes referred to 
as  fat 
phobia,  appears to be relatively more common in populations in Asia, where the 
rationale for dietary restriction is commonly related to a more culturally sanctioned complaint 
such as gastrointestinal 
discomfort. Mental 
health service utilization in the United States among 
individuals with an eating disorder is significantly lower among underserved ethnic and 
racialized groups. 


Diagnostic Markers 


The following laboratory abnormalities may be observed in anorexia nervosa; 
their presence may 


serve to increase diagnostic confidence. 
Hematology. 
Leukopenia is common, with the loss of all 
cell 
types but 
usually with apparent 
lymphocytosis. Mild anemia can occur, as well 
as thrombocytopenia and, rarely, bleeding 
problems. 


Serum chemistry. 
Dehydration may be reflected by an elevated blood urea nitrogen level. 
Hypercholesterolemia is common. Hepatic enzyme levels may 
be elevated. Hypomagnesemia, 
hypozincemia, hypophosphatemia, and hyperamylasemia are occasionally observed. Self-
induced vomiting may lead to metabolic alkalosis (elevated serum 
bicarbonate), hypochloremia, 
and hypokalemia; laxative abuse may cause a mild metabolic acidosis. 


Endocrine. 
Serum 
thyroxine (T4) levels are usually in the low-normal 
range; 
triiodothyronine 
(T3) levels are decreased, while reverse T3 
levels are elevated. Females have low serum 
estrogen 
levels, whereas males have low levels of serum testosterone. 
Electrocardiography. 
Sinus bradycardia is common, and, rarely, arrhythmias are noted. Significant 


prolongation of the QTc interval is observed in some individuals. 


Bone 
mass. 
Low bone mineral 
density, with specific areas of osteopenia or osteoporosis, is often 
seen. The risk of fracture is significantly elevated. 
Electroencephalography. 
Diffuse abnormalities, reflecting a metabolic encephalopathy, may result 


from significant fluid and electrolyte disturbances. 
Resting 
energy 
expenditure. 
There is often a significant reduction in resting energy expenditure. 



Physical 
signs 
and 
symptoms. 
Many of the physical 
signs and symptoms of anorexia nervosa are 
attributable to starvation. Amenorrhea is commonly present 
and appears to be an indicator of 
physiological 
dysfunction. If present, amenorrhea is usually a consequence of the weight 
loss, 
but 
in a minority of individuals it 
may actually precede the weight 
loss. In prepubertal 
females, 
menarche may be delayed. In addition to amenorrhea, there may be complaints of constipation, 
abdominal pain, cold intolerance, lethargy, and excess energy. 


386 


The most remarkable finding on physical examination is emaciation. Commonly, there is also 
significant 
hypotension, hypothermia, and bradycardia. Some individuals develop lanugo, a fine 
downy body hair. Some develop peripheral 
edema, especially during weight 
restoration or upon 
cessation of laxative and diuretic abuse. Rarely, petechiae or ecchymoses, usually on the 
extremities, may indicate a bleeding diathesis. Some individuals evidence a yellowing of the skin 
associated with hypercarotenemia. As may be seen in individuals with bulimia nervosa, 
individuals with anorexia nervosa who self-induce vomiting may have hypertrophy of the 
salivary glands, particularly the parotid glands, as well 
as dental 
enamel 
erosion. Some 
individuals may have scars or calluses on the dorsal 
surface of the hand from 
repeated contact 
with the teeth while inducing vomiting. 


Association With Suicidal 
Thoughts or Behavior 


Suicide risk is elevated in anorexia nervosa, with rates reported to be 18 times greater than in an 
age-and gender-matched comparison group. A systematic review found that 
suicide is the 
second leading cause of death in anorexia nervosa. Another review found that 
one-quarter to 
one-third of individuals with anorexia nervosa have suicidal 
ideation, and approximately 9%  
25% of individuals with anorexia nervosa have attempted suicide. Likely contributors to the 
increased risk for suicide in those with eating disorders include greater exposure to sexual 
abuse; 
impaired decision-making; 
high rates of nonsuicidal 
self-injury, a known risk factor for suicide 
attempts; and comorbidity with mood disorders. 


Functional 
Consequences of Anorexia Nervosa 


Individuals with anorexia nervosa may exhibit 
a range of functional 
limitations associated with 
the disorder. While some individuals remain active in social 
and professional 
functioning, others 
demonstrate significant social isolation and/or failure to fulfill academic or career potential. 


Differential 
Diagnosis 


In addition to the general 
consideration of differential 
diagnosis for all 
cases, it 
is especially 
important 
to consider other possible causes of either significantly low body weight 
or significant 
weight loss when the presenting features are atypical (e.g., onset after age 40 years). 


Medical 
conditions 
(e.g., 
gastrointestinal 
disease, 
hyperthyroidism, 
occult 
malignancies, 
and 
acquired 
immunodeficiency 
syndrome 
[AIDS]).

Serious weight 
loss may occur in medical 
conditions, but 
individuals with these disorders usually 
do not 
also manifest 
a disturbance in the way their body weight 
or shape is experienced or an 
intense fear of weight 
gain or persist 
in behaviors that 
interfere with appropriate weight 
gain. 



Acute weight 
loss associated with a medical 
condition can occasionally be followed by the onset 
or recurrence of anorexia nervosa, which can initially be masked by the comorbid medical 
condition. Rarely, anorexia nervosa develops after bariatric surgery. 


Major depressive 
disorder. 
In major depressive disorder, severe weight 
loss may occur, but 
most 
individuals with major depressive disorder do not 
have either a desire for excessive weight 
loss 
or an intense fear of gaining weight. 


Schizophrenia. 
Individuals with schizophrenia may exhibit 
odd eating behavior and occasionally 
experience significant 
weight 
loss, but 
they rarely show the fear of gaining weight 
and the body 
image disturbance required for a diagnosis of anorexia nervosa. 


Substance 
use 
disorders. 
Individuals with substance use disorders may experience low weight 
because of poor nutritional 
intake but 
generally do not 
fear gaining weight 
and do not 
manifest 
body image disturbance. Individuals who abuse substances that 
reduce appetite (e.g., cocaine, 
stimulants) and who also endorse fear of weight 
gain should be carefully evaluated for the 
possibility of comorbid anorexia nervosa, given that 
the substance use may represent 
a persistent 
behavior that interferes with weight gain (Criterion B). 


387 


Social 
anxiety 
disorder, 
obsessive-compulsive 
disorder, 
and 
body 
dysmorphic 
disorder. 


Some of the 
features of anorexia nervosa overlap with the criteria for social 
anxiety disorder, OCD, and body 
dysmorphic disorder. Specifically, individuals may feel 
humiliated or embarrassed to be seen 
eating in public, as in social 
anxiety disorder; 
may exhibit 
obsessions and compulsions related to 
food, as in OCD; 
or may be preoccupied with an imagined defect 
in bodily appearance, as in 
body dysmorphic disorder. If the individual 
with anorexia nervosa has social 
fears that 
are 
limited to eating behavior alone, the diagnosis of social 
anxiety disorder should not 
be made, but 
social 
fears unrelated to eating behavior (e.g., excessive fear of speaking in public) may warrant 
an additional 
diagnosis of social 
anxiety disorder. Similarly, an additional 
diagnosis of OCD 
should be considered only if the individual 
exhibits obsessions and compulsions unrelated to 
food (e.g., an excessive fear of contamination), and an additional 
diagnosis of body dysmorphic 
disorder should be considered only if the distortion is unrelated to body shape and size (e.g., 
preoccupation that one s nose is too big). 


Bulimia 
nervosa. 
Individuals with bulimia nervosa exhibit 
recurrent 
episodes of binge eating, 
engage in inappropriate behavior to avoid weight 
gain (e.g., self-induced vomiting), and are 
overly concerned with body shape and weight. However, unlike individuals with anorexia 
nervosa, binge-eating/purging type, individuals with bulimia nervosa maintain body weight 
at 
or 
above a minimally normal level. 


Avoidant/restrictive 
food 
intake 
disorder. 
Individuals with this disorder may exhibit 
significant 
weight 
loss or significant 
nutritional 
deficiency, but 
they do not 
have a fear of gaining weight 
or 
of becoming fat, nor do they have a disturbance in the way they experience their body shape and 
weight. 


Comorbidity 


Bipolar, depressive, and anxiety disorders commonly co-occur with anorexia nervosa. Many 



individuals with anorexia nervosa report 
the presence of either an anxiety disorder or symptoms 
of anxiety prior to onset 
of their eating disorder. OCD is described in some individuals with 
anorexia nervosa, especially those with the restricting type. Alcohol 
use disorder and other 
substance use disorders may also be comorbid with anorexia nervosa, especially among those 
with the binge-eating/purging type. 


Bulimia Nervosa 


Diagnostic Criteria 
F50.2 


A. 
Recurrent 
episodes of 
binge 
eating. 
An 
episode 
of 
binge 
eating 
is characterized 
by both 
of 
the 
following: 
1. 
Eating, 
in 
a 
discrete 
period 
of 
time 
(e.g., 
within 
any 2-hour period), 
an 
amount 
of 
food 
that 
is definitely larger than 
what 
most 
individuals would 
eat 
in 
a 
similar period 
of 
time 
under similar circumstances. 
2. 
A 
sense 
of 
lack of 
control over eating 
during 
the 
episode 
(e.g., 
a 
feeling 
that 
one 
cannot 
stop 
eating 
or control what 
or how much 
one 
is eating). 
B. 
Recurrent 
inappropriate 
compensatory behaviors in 
order to 
prevent 
weight 
gain, 
such 
as self-induced 
vomiting; 
misuse 
of 
laxatives, 
diuretics, 
or other 
medications; 
fasting; 
or excessive 
exercise. 
C. 
The 
binge 
eating 
and 
inappropriate 
compensatory behaviors both 
occur, 
on 
average, 
at 
least 
once 
a 
week for 3 
months. 
D. 
Self-evaluation 
is unduly influenced 
by body shape 
and 
weight. 
E. 
The 
disturbance 
does not 
occur exclusively during 
episodes of 
anorexia 
nervosa. 
388 


Specify 
if: 


In 
partial 
remission: 
After full criteria 
for bulimia 
nervosa 
were 
previously met, 
some, 
but 
not 
all, 
of 
the 
criteria 
have 
been 
met 
for a 
sustained 
period 
of 
time. 
In 
full 
remission: 
After full criteria 
for bulimia 
nervosa 
were 
previously met, 


none 
of 
the 
criteria 
have 
been 
met 
for a 
sustained 
period 
of 
time. 
Specify 
current 
severity: 
The 
minimum level of 
severity is based 
on 
the 
frequency of 
inappropriate 


compensatory behaviors (see 
below). 
The 
level of 
severity may be 
increased 
to 


reflect 
other symptoms and 
the 
degree 
of 
functional disability. 
Mild: 
An 
average 
of 
1 3 
episodes of 
inappropriate 
compensatory behaviors per 
week. 


Moderate: 
An 
average 
of 
4 7 
episodes of 
inappropriate 
compensatory 
behaviors per week. 



Severe: 
An 
average 
of 
8 13 
episodes of 
inappropriate 
compensatory behaviors 


per week. 
Extreme: 
An 
average 
of 
14 
or more 
episodes of 
inappropriate 
compensatory 
behaviors per week. 


Diagnostic Features 


There are three essential 
features of bulimia nervosa: 
recurrent 
episodes of binge eating 
(Criterion A), recurrent 
inappropriate compensatory behaviors to prevent 
weight 
gain (Criterion 
B), and self-evaluation that 
is unduly influenced by body shape and weight 
(Criterion D). To 
qualify for the diagnosis, the binge eating and inappropriate compensatory behaviors must 
occur, 
on average, at least once per week for 3 months (Criterion C). 


An  episode of binge eating  is defined as eating, in a discrete period of time, an amount 
of 
food that 
is definitely larger than most 
individuals would eat 
in a similar period of time under 
similar circumstances (Criterion A1). The context 
in which the eating occurs may affect 
the 
clinician s estimation of whether the intake is excessive. For example, a quantity of food that 
might 
be regarded as excessive for a typical 
meal 
might 
be considered normal 
during a 
celebration or holiday meal. A  discrete period of time  refers to a limited period, usually less 
than 2 hours. A single episode of binge eating need not 
be restricted to one setting. For example, 
an individual 
may begin a binge in a restaurant 
and then continue to eat 
on returning home. 
Continual 
snacking on small 
amounts of food throughout 
the day would not 
be considered an 
eating binge. 


An occurrence of excessive food consumption must 
be accompanied by a sense of lack of 
control 
(Criterion A2) to be considered an episode of binge eating. An indicator of loss of control 
is the inability to refrain from 
eating or to stop eating once started. Some individuals describe a 
dissociative quality during, or following, the binge-eating episodes. The impairment 
in control 
associated with binge eating may not 
be absolute; 
for example, an individual 
may continue binge 
eating while the telephone is ringing but 
will 
cease if a roommate or spouse unexpectedly enters 
the room. Some individuals report 
that 
their binge-eating episodes are no longer characterized by 
an acute feeling of loss of control 
but 
rather by a more generalized pattern of uncontrolled eating. 
If individuals report 
that 
they have abandoned efforts to control 
their eating, loss of control 
should be considered as present. Binge eating can also be planned in some instances. 


The type of food consumed during binges varies both across individuals and for a given 
individual. Binge eating appears to be characterized more by an abnormality in the amount 
of 
food consumed than by a craving for a specific nutrient. However, during binges, individuals 
tend to eat foods they would otherwise avoid. 


Individuals with bulimia nervosa are typically ashamed of their eating problems and attempt 
to conceal 
their symptoms. Binge eating usually occurs in secrecy or as inconspicuously as 
possible. The binge eating often continues until 
the individual 
is uncomfortably, or even 
painfully, full. The most common antecedent of binge eating is negative affect. 


389 


Other triggers include interpersonal 
stressors; 
dietary restraint; 
negative feelings related to 
body weight, body shape, and food; 
and boredom. Binge eating may minimize or mitigate factors 



that 
precipitated the episode in the short-term, but 
negative self-evaluation and dysphoria often 
are the delayed consequences. 


Another essential 
feature of bulimia nervosa is the recurrent 
use of inappropriate 
compensatory behaviors to prevent 
weight 
gain (Criterion B). Many individuals with bulimia 
nervosa employ several 
methods to compensate for binge eating. Self-induced vomiting, a type 
of purging behavior, is the most 
common inappropriate compensatory behavior. The immediate 
effects of vomiting include relief from 
physical 
discomfort 
and reduction of fear of gaining 
weight. In some cases, vomiting becomes a goal 
in itself, and the individual 
will 
binge eat 
in 
order to vomit 
or will 
vomit 
after eating a small 
amount 
of food. Individuals with bulimia 
nervosa may use a variety of methods to induce vomiting, including the use of fingers or 
instruments to stimulate the gag reflex. Individuals generally become adept 
at 
inducing vomiting 
and are eventually able to vomit 
at 
will. Rarely, individuals consume syrup of ipecac to induce 
vomiting. Other purging behaviors include the misuse of laxatives and diuretics and, in rare 
cases, the misuse of enemas following episodes of binge eating, although this is seldom 
the sole 
compensatory method employed. A number of compensatory methods other than purging may 
also be used in rare cases. Some individuals may take thyroid hormone in an attempt 
to avoid 
weight 
gain. Individuals with diabetes mellitus and bulimia nervosa may omit 
or reduce insulin 
doses in order to reduce the metabolism 
of food consumed during eating binges. Individuals with 
bulimia nervosa may fast 
for a day or more or exercise excessively in an attempt 
to prevent 
weight 
gain. Exercise may be considered excessive when it 
significantly interferes with 
important 
activities, when it 
occurs at 
inappropriate times or in inappropriate settings, or when 
the individual continues to exercise despite injury or other medical complications. 


Individuals with bulimia nervosa place an excessive emphasis on body shape or weight 
in 
their self-evaluation, and these factors are typically extremely important 
in determining self-
esteem 
(Criterion D). Individuals with this disorder may closely resemble those with anorexia 
nervosa in their fear of gaining weight, in their desire to lose weight, and in the level 
of 
dissatisfaction with their bodies. However, a diagnosis of bulimia nervosa should not 
be given 
when the disturbance occurs only during episodes of anorexia nervosa (Criterion E). 


Associated Features 


Individuals with bulimia nervosa typically are within the normal 
weight 
or overweight 
range 
(body mass index [BMI] = 
18.5 and < 
30 in adults). The disorder occurs but 
is uncommon 
among obese individuals. Between eating binges, individuals with bulimia nervosa typically 
restrict 
their total 
caloric consumption and preferentially select 
low-calorie ( diet ) foods while 
avoiding foods that they perceive to be fattening or likely to trigger a binge. 


Menstrual 
irregularity or amenorrhea often occurs among females with bulimia nervosa; 
it 
is 
uncertain whether such disturbances are related to weight 
fluctuations, to nutritional 
deficiencies, 
or to emotional 
distress. The fluid and electrolyte disturbances resulting from 
the purging 
behavior are sometimes sufficiently severe to constitute medically serious problems. Rare but 
potentially fatal 
complications include esophageal 
tears, gastric rupture, and cardiac arrhythmias. 
Serious cardiac and skeletal 
myopathies have been reported among individuals following 
repeated use of syrup of ipecac to induce vomiting. Individuals who chronically abuse laxatives 
may become dependent 
on their use to stimulate bowel 
movements. Gastrointestinal 
symptoms 
are commonly associated with bulimia nervosa, and rectal prolapse has also been reported among 



individuals with this disorder. 


Prevalence 


According to two U.S. epidemiological 
studies conducted in adult 
community samples, the 12month 
prevalence of bulimia nervosa ranges from 0.14% to 0.3%, with much higher 


390 


rates in women than in men (0.22% to 0.5% in women; 
0.05% to 0.1% in men), and the lifetime 
prevalence ranges from 
0.28% to 1.0% (0.46% to 1.5% in women; 
0.05% to 0.08% in men). In 
one study of adolescents ages 13 18, lifetime prevalence rates were 1.3% and 0.5% in girls and 
boys, respectively. 


In the United States, the prevalence of bulimia nervosa is similar across U.S. ethnoracial 
groups. The reported prevalence of bulimia nervosa is highest 
in populations residing in high-
income industrialized countries, such as the United States, Canada, Australia, New Zealand, and 
many European countries; 
in most 
of these countries the prevalence of bulimia nervosa is 
roughly comparable. 


The prevalence of bulimia nervosa in some regions of Latin America and the Middle East 
is 
similar to the prevalence in most 
high-income countries. The prevalence of bulimia nervosa 
appears to be gradually increasing in many low- and middle-income countries. 


Development and Course 


Bulimia nervosa commonly begins in adolescence or young adulthood. Onset 
before puberty or 
after age 40 is uncommon. The binge eating frequently begins during or after an episode of 
dieting to lose weight. Experiencing multiple stressful 
life events also can precipitate onset 
of 
bulimia nervosa. 


Disturbed eating behavior persists for at 
least 
several 
years in a high percentage of clinical 
samples. The course may be chronic or intermittent, with periods of remission alternating with 
recurrences of binge eating. However, over longer-term 
follow-up, the symptoms of many 
individuals appear to diminish with or without 
treatment, although treatment 
clearly impacts 
outcome. Periods of remission longer than 1 year are associated with better long-term outcome. 


Significantly elevated risk for mortality (all-cause and suicide) has been reported for 
individuals with bulimia nervosa. The crude mortality rate (ratio of the number of deaths during 
the year to the average population in that year) for bulimia nervosa is nearly 2% per decade. 


Diagnostic crossover from 
initial 
bulimia nervosa to anorexia nervosa occurs in a minority of 
cases (10% 15%). Individuals who do experience crossover to anorexia nervosa commonly will 
revert 
back to bulimia nervosa or have multiple occurrences of crossovers between these 
disorders. A subset 
of individuals with bulimia nervosa continue to binge eat 
but 
no longer 
engage in inappropriate compensatory behaviors, and therefore their symptoms meet 
criteria for 
binge-eating disorder or other specified eating disorder. Diagnosis should be based on the current 
(i.e., past 3 months) clinical presentation. 


Risk and Prognostic Factors 


Temperamental. 
Weight 
concerns, low self-esteem, depressive symptoms, social 
anxiety disorder, 



and childhood generalized anxiety disorder are associated with increased risk for the 


development of bulimia nervosa. 
Environmental. 
Internalization of a thin body ideal 
has been found to increase risk for developing 
weight 
concerns, which in turn increases risk for the development 
of bulimia nervosa. 
Individuals who experienced childhood sexual 
or physical 
abuse are at 
increased risk for 
developing bulimia nervosa. 


Genetic 
and 
physiological. 
Childhood obesity and early pubertal 
maturation increase risk for 
bulimia nervosa. Familial 
transmission of bulimia nervosa may be present, as well 
as genetic 
vulnerabilities for the disorder. 


Course 
modifiers. 
Severity of psychiatric comorbidity predicts worse long-term 
outcome of 
bulimia nervosa. 


391 


Culture-Related Diagnostic Issues 


Although data show that 
community-based prevalence of bulimia nervosa does not 
differ 
significantly across U.S. ethnoracial 
groups, treatment 
utilization for bulimia nervosa is lower 
among underserved U.S. ethnic and racialized groups than among the non-Latinx White 
population. 


Sex- and Gender-Related Diagnostic Issues 


Bulimia nervosa is much more common in girls and women than in boys and men. Boys and men 
are especially underrepresented in treatment-seeking samples, for reasons that 
have not 
yet 
been 
systematically examined. 


Diagnostic Markers 


No specific diagnostic test 
for bulimia nervosa currently exists. However, several 
laboratory 
abnormalities may occur as a consequence of purging and may increase diagnostic certainty. 
These include fluid and electrolyte abnormalities, such as hypokalemia (which can provoke 
cardiac arrhythmias), hypochloremia, and hyponatremia. The loss of gastric acid through 
vomiting may produce a metabolic alkalosis (elevated serum 
bicarbonate), and the frequent 
induction of diarrhea or dehydration through laxative and diuretic abuse can cause metabolic 
acidosis. Some individuals with bulimia nervosa exhibit mildly elevated levels of serum amylase, 
probably reflecting an increase in the salivary isoenzyme. 


Physical 
examination usually yields no physical 
findings. However, inspection of the mouth 
may reveal 
significant 
and permanent 
loss of dental 
enamel, especially from 
lingual 
surfaces of 
the front 
teeth because of recurrent 
vomiting. These teeth may become chipped and appear 
ragged and  moth-eaten.  There may also be an increased frequency of dental 
caries. In some 
individuals, the salivary glands, particularly the parotid glands, may become notably enlarged. 
Individuals who induce vomiting by manually stimulating the gag reflex may develop calluses or 
scars on the dorsal 
surface of the hand from 
repeated contact 
with the teeth. Serious cardiac and 
skeletal 
myopathies have been reported among individuals following repeated use of syrup of 
ipecac to induce vomiting. 



Association With Suicidal 
Thoughts or Behavior 


Suicide risk is elevated in bulimia nervosa. A review found that 
approximately one-quarter to 
one-third of individuals with bulimia nervosa have had suicidal 
ideation, and a similar proportion 
have attempted suicide. 


Functional 
Consequences of Bulimia Nervosa 


Individuals with bulimia nervosa may exhibit 
a range of functional 
limitations associated with 
the disorder and have reduced health-related quality of life. A minority of individuals report 
severe role impairment, with the social-life domain most 
likely to be adversely affected by 
bulimia nervosa. 


Differential 
Diagnosis 


Anorexia 
nervosa, 
binge-eating/purging 
type. 
Individuals whose binge-eating behavior occurs only 
during episodes of anorexia nervosa are given the diagnosis anorexia nervosa, binge-
eating/purging type, and should not 
be given the additional 
diagnosis of bulimia nervosa. For 
individuals with an initial 
diagnosis of anorexia nervosa who binge and purge but 
whose 
presentation no longer meets the full 
criteria for anorexia nervosa, binge-eating/purging type 
(e.g., when weight 
is normal), a diagnosis of bulimia nervosa should be given only when all 
criteria for bulimia nervosa have been met for at least 3 months. 


392 


Binge-eating 
disorder. 
Some individuals binge eat 
but 
do not 
engage in regular inappropriate 
compensatory behaviors. In these cases, the diagnosis of binge-eating disorder should be 
considered. 


Kleine-Levin 
syndrome. 
In certain neurological 
or other medical 
conditions, such as Kleine-Levin 
syndrome, there is disturbed eating behavior, but 
the characteristic psychological 
features of 
bulimia nervosa, such as overconcern with body shape and weight, are not present. 
Major depressive 
disorder, 
with 
atypical 
features. 
Overeating is common in major depressive 


disorder, with atypical 
features, but 
individuals with this disorder do not 
engage in inappropriate 
compensatory behaviors and do not 
exhibit 
the excessive concern with body shape and weight 
characteristic of bulimia nervosa. If criteria for both disorders are met, both diagnoses should be 
given. 


Borderline 
personality 
disorder. 
Binge-eating behavior is included in the impulsive behavior 
criterion that 
is part 
of the definition of borderline personality disorder. If the criteria for both 
borderline personality disorder and bulimia nervosa are met, both diagnoses should be given. 


Comorbidity 


Comorbidity with mental 
disorders is common in individuals with bulimia nervosa, with most 
experiencing at 
least 
one other mental 
disorder and many experiencing multiple comorbidities. 
Comorbidity is not 
limited to any particular subset 
but 
rather occurs across a wide range of 
mental 
disorders. There is an increased frequency of depressive symptoms (e.g., low self-esteem) 
and bipolar and depressive disorders (particularly depressive disorders) in individuals with 



bulimia nervosa. In many individuals, the mood disturbance begins at 
the same time as or 
following the development 
of bulimia nervosa, and individuals often ascribe their mood 
disturbances to the bulimia nervosa. However, in some individuals, the mood disturbance clearly 
precedes the development 
of bulimia nervosa. There may also be an increased frequency of 
anxiety symptoms (e.g., fear of social 
situations) or anxiety disorders. These mood and anxiety 
disturbances frequently remit 
following effective treatment 
of the bulimia nervosa. The lifetime 
prevalence of substance use disorder, particularly alcohol 
use disorder or stimulant 
use disorder, 
is at 
least 
30% among individuals with bulimia nervosa. Stimulant 
use often begins in an attempt 
to control 
appetite and weight. A substantial 
percentage of individuals with bulimia nervosa also 
have personality features that 
meet 
criteria for one or more personality disorders, most 
frequently 
borderline personality disorder. 


Binge-Eating 
Disorder 


Diagnostic Criteria 
F50.81 


A. 
Recurrent 
episodes of 
binge 
eating. 
An 
episode 
of 
binge 
eating 
is characterized 
by both 
of 
the 
following: 
1. 
Eating, 
in 
a 
discrete 
period 
of 
time 
(e.g., 
within 
any 2-hour period), 
an 
amount 
of 
food 
that 
is definitely larger than 
what 
most 
people 
would 
eat 
in 
a 
similar 
period 
of 
time 
under similar circumstances. 
2. 
A 
sense 
of 
lack of 
control over eating 
during 
the 
episode 
(e.g., 
a 
feeling 
that 
one 
cannot 
stop 
eating 
or control what 
or how much 
one 
is eating). 
B. 
The 
binge-eating 
episodes are 
associated 
with 
three 
(or more) of 
the 
following: 
1. 
Eating 
much 
more 
rapidly than 
normal. 
2. 
Eating 
until feeling 
uncomfortably full. 
393 


3. 
Eating 
large 
amounts of 
food 
when 
not 
feeling 
physically hungry. 
4. 
Eating 
alone 
because 
of 
feeling 
embarrassed 
by how much 
one 
is eating. 
5. 
Feeling 
disgusted 
with 
oneself, 
depressed, 
or very guilty afterward. 
C. 
Marked 
distress regarding 
binge 
eating 
is present. 
D. 
The 
binge 
eating 
occurs, 
on 
average, 
at 
least 
once 
a 
week for 3 
months. 
E. 
The 
binge 
eating 
is not 
associated 
with 
the 
recurrent 
use 
of 
inappropriate 
compensatory behavior as in 
bulimia 
nervosa 
and 
does not 
occur exclusively 
during 
the 
course 
of 
bulimia 
nervosa 
or anorexia 
nervosa. 
Specify 
if: 
In 
partial 
remission: 
After full criteria 
for binge-eating 
disorder were 
previously 
met, 
binge 
eating 
occurs at 
an 
average 
frequency of 
less than 
one 
episode 
per 



week for a 
sustained 
period 
of 
time. 
In 
full 
remission: 
After full criteria 
for binge-eating 
disorder were 
previously met, 


none 
of 
the 
criteria 
have 
been 
met 
for a 
sustained 
period 
of 
time. 
Specify 
current 
severity: 
The 
minimum level of 
severity is based 
on 
the 
frequency of 
episodes of 
binge 
eating 


(see 
below). 
The 
level of 
severity may be 
increased 
to 
reflect 
other symptoms and 
the 
degree 
of 
functional disability. 


Mild: 
1 3 
binge-eating 
episodes per week. 


Moderate: 
4 7 
binge-eating 
episodes per week. 


Severe: 
8 13 
binge-eating 
episodes per week. 


Extreme: 
14 
or more 
binge-eating 
episodes per week. 


Diagnostic Features 


The essential 
feature of binge-eating disorder is recurrent 
episodes of binge eating that 
must 
occur, on average, at 
least 
once per week for 3 months (Criterion D). An  episode of binge 
eating  is defined as eating, in a discrete period of time, an amount 
of food that 
is definitely 
larger than most 
people would eat 
in a similar period of time under similar circumstances 
(Criterion A1). The context 
in which the eating occurs may affect 
the clinician s estimation of 
whether the intake is excessive. For example, a quantity of food that 
might 
be regarded as 
excessive for a typical 
meal 
might 
be considered normal 
during a celebration or holiday meal. A 
 discrete period of time  refers to a limited period, usually less than 2 hours. A single episode of 
binge eating need not 
be restricted to one setting. For example, an individual 
may begin a binge 
in a restaurant 
and then continue to eat 
on returning home. Continual 
snacking on small 
amounts 
of food throughout the day would not be considered an eating binge. 


An occurrence of excessive food consumption must 
be accompanied by a sense of lack of 
control 
(Criterion A2) to be considered an episode of binge eating. An indicator of loss of control 
is the inability to refrain from 
eating or to stop eating once started. Some individuals describe a 
dissociative quality during, or following, the binge-eating episodes. The impairment 
in control 
associated with binge eating may not 
be absolute; 
for example, an individual 
may continue binge 
eating while the telephone is ringing but 
will 
cease if a roommate or spouse unexpectedly enters 
the room. Some individuals report 
that 
their binge-eating episodes are no longer characterized by 
an acute feeling of loss of control 
but 
rather by a more generalized pattern of uncontrolled eating. 
If individuals report 
that 
they have abandoned efforts to control 
their eating, loss of control 
may 
still be considered as present. Binge eating can also be planned in some instances. 


The type of food consumed during binges varies both across individuals and for a given 
individual. Binge eating appears to be characterized more by an abnormality in the amount 
of 
food consumed than by a craving for a specific nutrient. 


394 


Binge eating must 
be characterized by marked distress (Criterion C) and at 
least 
three of the 
following features: 
eating much more rapidly than normal; 
eating until 
feeling uncomfortably 



full; 
eating large amounts of food when not 
feeling physically hungry; 
eating alone because of 
feeling embarrassed by how much one is eating; and feeling disgusted with oneself, depressed, or 
very guilty afterward (Criterion B). 


Individuals with binge-eating disorder are typically ashamed of their eating problems and 
attempt 
to conceal 
their symptoms. Binge eating usually occurs in secrecy or as inconspicuously 
as possible. The most 
common antecedent 
of binge eating is negative affect. Other triggers 
include interpersonal 
stressors; 
dietary restraint; 
negative feelings related to body weight, body 
shape, and food; 
and boredom. Binge eating may minimize or mitigate factors that 
precipitated 
the episode in the short-term, but 
negative self-evaluation and dysphoria often are the delayed 
consequences. 


Associated Features 


Binge-eating disorder occurs in normal-weight/overweight 
and obese individuals. It 
is reliably 
associated with overweight 
and obesity in treatment-seeking individuals. Nevertheless, binge-
eating disorder is distinct 
from 
obesity. Most 
obese individuals do not 
engage in recurrent 
binge 
eating. In addition, compared with weight-matched obese individuals without 
binge-eating 
disorder, those with the disorder consume more calories in laboratory studies of eating behavior 
and have greater functional 
impairment, lower quality of life, more subjective distress, and 
greater psychiatric comorbidity. 


Prevalence 


According to two U.S. epidemiological 
studies conducted in community samples, the 12-month 
prevalence of binge-eating disorder ranges from 
0.44% to 1.2%, with rates two to three times 
higher in women than in men (0.6% to 1.6% in women; 
0.26% to 0.8% in men), and the lifetime 
prevalence ranges from 0.85% to 2.8% (1.25% to 3.5% in women; 0.42% to 2.0% in men). 


In the United States, the prevalence of binge-eating disorder appears comparable across 
ethnoracial groups. 


Binge-eating disorder has a roughly similar prevalence in most 
high-income industrialized 
countries, including the United States, Canada, many European countries, Australia, and New 
Zealand, with 12-month prevalence in high-income countries ranging from 
0.1% to 1.2%. 
Although fewer data are available from 
populations in low- and 
middle-income countries, binge-
eating disorder prevalence in some regions of Latin America appears to be at 
least 
as high as in 
the United States and Europe. Mexican Americans in the United States have a higher prevalence 
of binge-eating disorder than their counterparts in Mexico. 


Development and Course 


Little is known about 
the development 
of binge-eating disorder. Both binge eating and loss-ofcontrol 
eating without 
objectively excessive consumption occur in children and are associated 
with increased body fat, weight 
gain, and increases in psychological 
symptoms. Binge eating is 
common in adolescent 
and college-age samples. Loss-of-control 
eating or episodic binge eating 
may represent a prodromal phase of eating disorders for some individuals. 


Dieting follows the development 
of binge eating in many individuals with binge-eating 
disorder. (This is in contrast 
to bulimia nervosa, in which dysfunctional 
dieting usually precedes 



the onset 
of binge eating.) Binge-eating disorder typically begins in adolescence or young 
adulthood but 
can begin in later adulthood. Individuals with binge-eating disorder who seek 
treatment 
usually are older than individuals with either bulimia nervosa or anorexia nervosa who 
seek treatment. 


395 


Remission rates in both natural 
course and treatment 
outcome studies are higher for binge-
eating disorder than for bulimia nervosa or anorexia nervosa. The course of binge-eating disorder 
is variable and as yet 
incompletely understood, with at 
least 
some affected individuals showing a 
relatively persistent, at 
times relapsing and remitting, symptom 
trajectory comparable to that 
of 
bulimia nervosa in terms of severity and duration. Crossover from 
binge-eating disorder to other 
eating disorders is uncommon. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Binge-eating disorder appears to run in families, which may reflect 
additive genetic influences. 


Culture-Related Diagnostic Issues 


Clinical 
presentations of binge-eating disorder differ across ethnoracial 
groups in the United 
States. Black individuals may report fewer symptoms of distress associated with binge eating and 
present for treatment with higher frequency of binge eating compared with White individuals. 


Association With Suicidal 
Thoughts or Behavior 


Suicidal 
ideation has been reported to occur in approximately 25% of individuals with binge-
eating disorder. 


Functional 
Consequences of Binge-Eating Disorder 


Binge-eating disorder is associated with a range of functional 
consequences, including social 
role 
adjustment 
problems, impaired health-related quality of life and life satisfaction, increased 
medical 
morbidity and mortality, and associated increased health care utilization compared with 
body mass index (BMI) matched control 
subjects. It 
may also be associated with an increased 
risk for weight gain and the development of obesity. 


Differential 
Diagnosis 


Bulimia 
nervosa. 
Binge-eating disorder has recurrent 
binge eating in common with bulimia 
nervosa but 
differs from 
the latter disorder in some fundamental 
respects. In terms of clinical 
presentation, the recurrent 
inappropriate compensatory behavior (e.g., purging, driven exercise) 
seen in bulimia nervosa is absent 
in binge-eating disorder. Unlike individuals with bulimia 
nervosa, individuals with binge-eating disorder typically do not 
show marked or sustained 
dietary restriction designed to influence body weight 
and shape between binge-eating episodes. 
They may, however, report 
frequent 
attempts at 
dieting. Binge-eating disorder also differs from 
bulimia nervosa in terms of response to treatment. Rates of improvement 
are consistently higher 



among individuals with binge-eating disorder than among those with bulimia nervosa. 
Obesity. 
Binge-eating disorder is associated with overweight 
and obesity but 
has several 
key 
features that 
are distinct 
from 
obesity. First, levels of overvaluation of body weight 
and shape are 
higher in obese individuals with the disorder than in those without 
the disorder. Second, rates of 
psychiatric comorbidity are significantly higher among obese individuals with the disorder 
compared with those without 
the disorder. Third, the outcome of evidence-based psychological 


treatments for binge-eating disorder is more often successful 
than the treatment 
of obesity in 
individuals with comorbid obesity and binge-eating disorder. 
Bipolar and 
depressive 
disorders. 
Increases in appetite and weight 
gain are included in the criteria 


for major depressive episode and in the atypical features specifiers for 


396 


depressive and bipolar disorders. Increased eating in the context 
of a major depressive episode 
may or may not 
be associated with loss of control. If the full 
criteria for both disorders are met, 
both diagnoses can be given. Binge eating and other symptoms of disordered eating are seen in 
association with bipolar disorder. If the full 
criteria for both disorders are met, both diagnoses 
should be given. 


Borderline 
personality 
disorder. 
Binge eating is included in the impulsive behavior criterion that 
is 
part 
of the definition of borderline personality disorder. If the full 
criteria for both disorders are 
met, both diagnoses should be given. 


Comorbidity 


Binge-eating disorder is associated with significant 
psychiatric comorbidity that 
is comparable to 
that 
of bulimia nervosa and anorexia nervosa. The most 
common comorbid disorders are major 
depressive disorder and alcohol 
use disorder. The psychiatric comorbidity is linked to the 
severity of binge eating and not to the degree of obesity. 


Other Specified 
Feeding 
or Eating 
Disorder 


F50.89 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
feeding 
and 
eating 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
feeding 
and 
eating 
disorders diagnostic 
class. 
The 
other specified 
feeding 
or eating 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific feeding 
and 
eating 
disorder. 
This is done 
by recording 
 other specified 
feeding 
or eating 
disorder  followed 
by the 
specific 
reason 
(e.g., 
 bulimia 
nervosa 
of 
low frequency ). 


Examples of 
presentations that 
can 
be 
specified 
using 
the 
 other specified  
designation 
include 
the 
following: 



1. 
Atypical 
anorexia 
nervosa: 
All of 
the 
criteria 
for anorexia 
nervosa 
are 
met, 
except 
that 
despite 
significant 
weight 
loss, 
the 
individual s weight 
is within 
or 
above 
the 
normal range. 
Individuals with 
atypical anorexia 
nervosa 
may 
experience 
many of 
the 
physiological complications associated 
with 
anorexia 
nervosa. 
2. 
Bulimia 
nervosa 
(of low 
frequency 
and/or limited 
duration): 
All of 
the 
criteria 
for bulimia 
nervosa 
are 
met, 
except 
that 
the 
binge 
eating 
and 
inappropriate 
compensatory behaviors occur, 
on 
average, 
less than 
once 
a 
week and/or for 
less than 
3 
months. 
3. 
Binge-eating 
disorder (of low 
frequency 
and/or limited 
duration): 
All of 
the 
criteria 
for binge-eating 
disorder are 
met, 
except 
that 
the 
binge 
eating 
occurs, 
on 
average, 
less than 
once 
a 
week and/or for less than 
3 
months. 
4. 
Purging 
disorder: 
Recurrent 
purging 
behavior to 
influence 
weight 
or shape 
(e.g., 
self-induced 
vomiting; 
misuse 
of 
laxatives, 
diuretics, 
or other medications) 
in 
the 
absence 
of 
binge 
eating. 
5. 
Night eating 
syndrome: 
Recurrent 
episodes of 
night 
eating, 
as manifested 
by 
eating 
after awakening 
from sleep 
or by excessive 
food 
consumption 
after the 
evening 
meal. 
There 
is awareness and 
recall of 
the 
eating. 
The 
night 
eating 
is 
not 
better explained 
by external influences such 
as changes in 
the 
individual s 
sleep-wake 
cycle 
or by local social norms. 
The 
night 
eating 
causes significant 
distress and/or impairment 
in 
functioning. 
The 
disordered 
pattern 
of 
eating 
is not 
better explained 
by binge-eating 
disorder or another mental disorder, 
including 
substance 
use, 
and 
is not 
attributable 
to 
another medical condition 
or to 
an 
effect 
of 
medication. 
397 


Unspecified 
Feeding 
or Eating 
Disorder 


F50.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
feeding 
and 
eating 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
feeding 
and 
eating 
disorders diagnostic 
class. 
The 
unspecified 
feeding 
or eating 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for 
a 
specific feeding 
and 
eating 
disorder and 
includes presentations in 
which 
there 
is 
insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room 
settings). 


398 



399 



Elimination Disorders 


Elimination disorders 
all 
involve the inappropriate elimination of urine or feces and 
are usually first 
diagnosed in childhood or adolescence. This group of disorders includes 
enuresis, 
the repeated voiding of urine into inappropriate places, and encopresis, 
the repeated 
passage of feces into inappropriate places. Subtypes are provided to differentiate nocturnal 
from 
diurnal 
(i.e., during waking hours) voiding for enuresis and the presence or absence of 
constipation and overflow incontinence for encopresis. Although there are minimum 
age 
requirements for diagnosis of both disorders, these are based on developmental 
age and not 
solely on chronological 
age. Both disorders may be voluntary or involuntary. Although these 
disorders typically occur separately, co-occurrence may also be observed. 


Enuresis 


Diagnostic Criteria 
F98.0 


A. 
Repeated 
voiding 
of 
urine 
into 
bed 
or clothes, 
whether involuntary or intentional. 
B. 
The 
behavior is clinically significant 
as manifested 
by either a 
frequency of 
at 
least 
twice 
a 
week for at 
least 
3 
consecutive 
months or the 
presence 
of 
clinically 
significant 
distress or impairment 
in 
social, 
academic (occupational), 
or other 
important 
areas of 
functioning. 
C. 
Chronological age 
is at 
least 
5 
years (or equivalent 
developmental level). 
D. 
The 
behavior is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
diuretic, 
an 
antipsychotic medication) or another medical condition 
(e.g., 
diabetes, 
spina 
bifida, 
a 
seizure 
disorder). 
Specify 
whether: 
Nocturnal 
only: 
Passage 
of 
urine 
only during 
nighttime 
sleep. 
Diurnal 
only: 
Passage 
of 
urine 
during 
waking 
hours. 
Nocturnal 
and 
diurnal: 
A 
combination 
of 
the 
two 
subtypes above. 


Subtypes 


The nocturnal-only subtype of enuresis, sometimes referred to as monosymptomatic enuresis, 
is 
the most 
common subtype and involves incontinence only during nighttime sleep, typically 
during the first 
one-third of the night. The diurnal-only subtype occurs in the absence of 
nocturnal 
enuresis and may be referred to simply as urinary incontinence. 
Individuals with this 



subtype can be divided into two groups. Individuals with  urge incontinence  have sudden urge 
symptoms and detrusor instability, whereas individuals with  voiding postponement  
consciously defer micturition urges until 
incontinence results. The nocturnal-and-diurnal 
subtype 
is also known as nonmonosymptomatic enuresis. 


400 


Diagnostic Features 


The essential 
feature of enuresis is repeated voiding of urine during the day or at 
night 
into bed 
or clothes (Criterion A). Most 
often the voiding is involuntary, but 
occasionally it 
may be 
intentional. To qualify for a diagnosis of enuresis, the voiding of urine must 
occur at 
least 
twice a 
week for at 
least 
3 consecutive months or must 
cause clinically significant 
distress or impairment 
in social, academic (occupational), or other important 
areas of functioning (Criterion B). The 
individual 
must 
have reached an age at 
which continence is expected (i.e., a chronological 
age of 
at 
least 
5 years or, for children with developmental 
delays, a mental 
age of at 
least 
5 years) 
(Criterion C). The urinary incontinence is not 
attributable to the physiological 
effects of a 
substance (e.g., a diuretic, an antipsychotic medication) or another medical 
condition (e.g., 
diabetes, spina bifida, ectopic ureter in a female, posterior urethral 
valves in a male, tethered 
cord, a seizure disorder) (Criterion D). 


Associated Features 


During nocturnal 
enuresis, occasionally the voiding takes place during rapid eye movement 
(REM) sleep, and the child may recall 
a dream 
that 
involved the act 
of urinating. During daytime 
(diurnal) enuresis, the child defers voiding until 
incontinence occurs, sometimes because of a 
reluctance to use the toilet 
as a result 
of social 
anxiety or a preoccupation with school 
or play 
activity. The enuretic events most 
commonly occur in the early afternoon on school 
days or after 
returning from 
school. Children with executive functioning problems and other neurological 
problems that 
may be associated with symptoms of disruptive behavior may be at 
high risk for 
urinary incontinence without 
sensory awareness. It 
is not 
uncommon for children with daytime 
urinary incontinence and the nocturnal-and-diurnal 
subtype of enuresis to have persistence of 
incontinence after appropriate treatment of an associated infection. 


Prevalence 


The prevalence of daytime incontinence ranges from 
3.2% to 9.0% in children age 7 years, from 
1.1% to 4.2% in youth ages 11 13 years, and from 
1.2% to 3.0% in adolescents ages 15 17 
years. 


The prevalence of nocturnal 
enuresis in the community decreases with age; 
in several 
geographical 
settings, including the United States, the Netherlands, and Hong Kong, the range is 
around 5% 10% among 5-year-olds, 3% 5% among 10-year-olds, and around 1% among 
individuals 15 years or older. Boys and members of socially oppressed groups may have higher 
prevalence as found in African American children in the United States and Turkish or Moroccan 
children in the Netherlands. The disorder may also have higher prevalence in youth with learning 
disabilities or attention-deficit/hyperactivity disorder. 



Development and Course 


Enuresis can follow two courses: 
a  primary  type, in which the individual 
has never established 
urinary continence, and a  secondary  type, in which the disturbance develops after a period of 
established urinary continence. There are no differences in prevalence of comorbid mental 
disorders between the two types. By definition, primary enuresis begins at 
age 5 years. The most 
common time for the onset 
of secondary enuresis is between ages 5 and 8 years, but 
it 
may occur 
at 
any time. After age 5 years, the rate of spontaneous remission is 5% 10% per year. Most 
children with the disorder become continent 
by adolescence, but 
in approximately 1% of cases 
the disorder continues into adulthood. Diurnal 
enuresis is uncommon after age 9 years. While 
occasional 
diurnal 
incontinence is not 
uncommon in middle childhood, it 
is substantially more 
common in those who also have other co-occurring mental 
health problems, including cognitive 
and behavioral 
problems. When enuresis persists into late childhood or adolescence, the 
incontinence may resolve, but 
urinary frequency generally persists and incontinence can recur 
later in adulthood in women. 


401 


Risk and Prognostic Factors 


A number of predisposing factors for bladder dysfunction have been suggested, including 


developmental delays and neuropsychiatric problems. 
Environmental. 
Factors recognized to be associated with bladder dysfunction include delayed 
toileting and psychosocial stress. 


Genetic 
and 
physiological. 


Nocturnal 
enuresis has been associated with a mismatch between 
nocturnal 
urine production, nocturnal 
bladder storage capacity, and the ability to arouse from 
sleep. Underlying these mechanisms are possibly disorders of central 
nervous system 
signal 
processing and the default 
mode network. The increased arousal 
thresholds do not, however, 
mean that 
these children sleep well; 
in fact, sleep quality of enuretic children is often poor. 
Nocturnal 
enuresis is a genetically heterogeneous disorder. Heritability has been shown in 
family, twin, and segregation analyses. Risk for childhood nocturnal 
enuresis is approximately 


3.6 times higher in offspring of enuretic mothers and 10.1 times higher in the presence of 
paternal 
urinary incontinence. The risk magnitudes for nocturnal 
enuresis and diurnal 
incontinence are similar. 
Culture-Related Diagnostic Issues 


Enuresis has been reported in a variety of European, African, and Asian countries as well 
as in 
the United States. At 
a national 
level, prevalence rates are remarkably similar, and there is great 
similarity in the developmental 
trajectories found in different 
countries. Local 
school-based 
surveys, however, show wide prevalence variation of nocturnal 
enuresis across settings in Africa, 
South Asia, Europe, and the Caribbean (4% 50%), at 
least 
in part 
due to methodological 
variation. The very high rates of enuresis in orphanages and other residential 
institutions are not 
explained by the mode or early timing of toilet training. 


Cultural 
contexts affect 
both the diagnosis and the perceived etiology of enuresis. For 
example, traditional 
Chinese medicine attributes enuresis to long-term 
kidney yang (masculine 



energy) deficiency. Heightened impact 
on parents of children s enuresis has been reported in 
societies with economic limitations in obtaining care for the child or in the context 
of social 
policies that 
restrict 
the number of children (e.g., China s one-child policy), possibly leading to 
higher risk of parental emotional disorders. 


Sex- and Gender-Related Diagnostic Issues 


Nocturnal 
enuresis is more common in males than in females (almost 
2:1). This male 
preponderance is particularly true in younger age groups, cases with milder severity, and cases 
involving enuresis occurring only at 
night. Urinary tract 
infections are frequently associated with 
daytime wetting, especially in females. Diurnal 
incontinence is more common in females than in 
males, and the ratio increases with age. The relative risk of having a child who develops enuresis 
is greater for previously enuretic fathers than for previously enuretic mothers. 


Functional 
Consequences of Enuresis 


The amount 
of impairment 
associated with enuresis is a function of the limitation on the child s 
social 
activities (e.g., ineligibility for sleep-away camp) or its effect 
on the child s self-esteem, 
the degree of social 
ostracism 
by peers, and the anger, punishment, and rejection on the part 
of 
caregivers. 


Differential 
Diagnosis 


Neurogenic 
bladder or another medical 
condition. 
The diagnosis of enuresis is not 
made in the 
presence of a neurogenic bladder or any other structural 
condition (such as a posterior urethral 
valve or ectopic ureter) or another medical condition that causes polyuria or 


402 


urgency (e.g., untreated diabetes mellitus or diabetes insipidus) or during an acute urinary tract 
infection. However, a diagnosis is compatible with such medical 
conditions if urinary 
incontinence was regularly present 
prior to the development 
of another medical 
condition or if it 
persists after the institution of appropriate treatment of the medical condition. 


Medication 
side 
effects. 
Enuresis may occur during treatment 
with antipsychotic medications, 
diuretics, or other medications that 
may induce constipation, polyuria, or alterations in executive 
functioning, all 
of which may lead to incontinence. In this case, the diagnosis should not 
be made 
in isolation but 
may be noted as a medication side effect. However, a diagnosis of enuresis may 
be made if urinary incontinence was regularly present prior to treatment with the medication. 


Comorbidity 


Although most 
children with enuresis do not 
have a comorbid mental 
disorder, the prevalence of 
comorbid behavioral 
and developmental 
symptoms is higher in children with both diurnal 
and 
nocturnal 
enuresis than in children without 
incontinence. Developmental 
delays, including 
speech, language, learning, and motor skills delays, are also present 
in a portion of children with 
enuresis. Encopresis and constipation are present 
in both day and night 
incontinence. Restless 
legs syndrome and parasomnias such as non rapid eye movement 
sleep arousal 
disorders 



(sleepwalking and sleep terror types) are associated with nocturnal 
enuresis. Additionally, there 
is a link between nocturnal 
enuresis and heavy snoring or sleep apneas. Approximately 50% of 
enuretic children with proven sleep-disordered breathing will 
become dry by undergoing 
adenotonsillectomy. Urinary tract 
infections are more common in children with daytime urinary 
incontinence and nonmonosymptomatic nocturnal 
enuresis, especially the diurnal 
subtype, than 
in those who are continent. 


Encopresis 


Diagnostic Criteria 
F98.1 


A. 
Repeated 
passage 
of 
feces into 
inappropriate 
places (e.g., 
clothing, 
floor), 
whether involuntary or intentional. 
B. 
At 
least 
one 
such 
event 
occurs each 
month 
for at 
least 
3 
months. 
C. 
Chronological age 
is at 
least 
4 
years (or equivalent 
developmental level). 
D. 
The 
behavior is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
laxatives) or another medical condition 
except 
through 
a 
mechanism involving 
constipation. 
Specify 
whether: 


With 
constipation 
and 
overflow 
incontinence: 
There 
is evidence 
of 
constipation 
on 
physical examination 
or by history. 
Without constipation 
and 
overflow 
incontinence: 
There 
is no 
evidence 
of 


constipation 
on 
physical examination 
or by history. 


Subtypes 


Feces in encopresis,  with constipation and overflow incontinence  subtype, are 
characteristically (but 
not 
invariably) poorly formed, and leakage can be infrequent 
to 
continuous, occurring throughout 
the day and at 
times during sleep. Only part 
of the feces is 
passed during toileting, and the incontinence resolves after treatment of the constipation. 


In the  without 
constipation and overflow incontinence  subtype, feces are likely to be of 
normal form and consistency, and soiling is intermittent. Feces may be deposited in a 


403 


prominent 
location. This is usually associated with the presence of oppositional 
defiant 
disorder or conduct 
disorder or may be the consequence of anal 
masturbation. Soiling without 
constipation is less common than soiling with constipation. 


Diagnostic Features 


The essential 
feature of encopresis is repeated passage of feces into inappropriate places (e.g., 
clothing or floor) (Criterion A). Most 
often the passage is involuntary but 
occasionally may be 



intentional. The event 
must 
occur at 
least 
once a month for at 
least 
3 months (Criterion B), and 
the chronological 
age of the child must 
be at 
least 
4 years (or for children with developmental 
delays, the mental 
age must 
be at 
least 
4 years) (Criterion C). The fecal 
incontinence must 
not 
be 
exclusively attributable to the physiological 
effects of a substance (e.g., laxatives) or another 
medical condition except through a mechanism involving constipation (Criterion D). 


When the passage of feces is involuntary rather than intentional, it 
is often related to 
constipation, impaction, and retention with subsequent 
overflow. The constipation may develop 
for psychological 
reasons (e.g., anxiety about 
defecating in a particular place, a more general 
pattern of anxious or oppositional 
behavior), leading to avoidance of defecation and excessive 
volitional 
stool 
retention. Physiological 
predispositions to constipation include ineffectual 
straining or paradoxical 
defecation dynamics, with contraction rather than relaxation of the 
external 
sphincter or pelvic floor during straining for defecation. Dietary habits (such as 
insufficient 
fluid intake), celiac disease, hypothyroidism, or a medication side effect 
can also 
induce constipation. Once constipation has developed, it 
may be complicated by an anal 
fissure, 
painful 
defecation, and further fecal 
retention. The consistency of the stool 
may vary. In some 
individuals the stool 
may be of normal 
or near-normal 
consistency. In other individuals such as 
those with overflow incontinence secondary to fecal retention it may be liquid. 


Associated Features 


The child with encopresis often feels ashamed and may wish to avoid situations (e.g., camp, 
school) that 
might 
lead to embarrassment. The amount 
of impairment 
is a function of the effect 
on the child's self-esteem, the degree of social 
ostracism 
by peers, and the anger, punishment, 
and rejection on the part 
of caregivers. Smearing feces may be deliberate or accidental, resulting 
from 
the child s attempt 
to clean or hide feces that 
were passed involuntarily. When the 
incontinence is clearly deliberate, features of oppositional 
defiant 
disorder or conduct 
disorder 
may also be present. Many children with encopresis and chronic constipation also have enuresis 
symptoms and may have associated urinary reflux in the bladder or ureters that 
may lead to 
chronic urinary infections, the symptoms of which may remit with treatment of the constipation. 


Prevalence 


It 
is estimated that 
the majority of children older than 4 years with encopresis have the subtype 
 with constipation and overflow incontinence.  Encopresis affects 1% 4% of children in high-
income countries, while in some Asian countries (Iran, South Korea, Sri 
Lanka) a prevalence of 
2% 8% has been reported. Encopresis is more prevalent 
among children ages 4 6 years (> 4%) 
than among children ages 10 12 years (< 2%); 
prevalence is also higher among children who 
experience early abuse or neglect and low-income youth. 


Development and Course 


Encopresis is not 
diagnosed until 
a child has reached a chronological 
age of at 
least 
4 years (or 
for children with developmental delays, a mental age of at least 4 years). Inadequate, 


404 


inconsistent 
toilet 
training and psychosocial 
stress (e.g., entering school, the birth of a sibling) 



may be predisposing factors. Two types of course have been described: 
a  primary  type, in 
which the individual has never established fecal continence, and a  secondary  type, in which the 
disturbance develops after a period of established fecal 
continence. Encopresis can persist, with 
intermittent exacerbations, for years. 


Risk and Prognostic Factors 


Painful 
defecation can lead to constipation and a cycle of withholding behaviors that 
make 
encopresis more likely. Male gender and age prior to adolescence are risk factors for encopresis. 
A number of factors are thought 
to contribute to the development 
of fecal 
incontinence, 
including anxiety, depression, behavioral 
disorders, psychological 
stressors (e.g., bullying, poor 
school performance), and lower socioeconomic status. 


Culture-Related Diagnostic Issues 


Differences in food and beverage intake in different 
cultures, hot 
climatic conditions in tropical 
countries, and psychosocial 
adversity may influence the incidence of constipation, unexplained 
abdominal 
pain, and fecal 
retention that 
lead to encopresis. Parents in some societies may not 
seek health services for encopresis because of sociocultural 
reasons. For example, Turkish and 
Moroccan parents in the Netherlands may not 
report 
encopresis because of religious concerns 
about the impurity of urine and feces. 


Sex- and Gender-Related Diagnostic Issues 


In children younger than 5 years, the gender ratio appears to be equal, but 
encopresis tends to be 
more common in boys than in girls among older children, with a ratio that 
varies globally (in 
community and hospital-based studies) from 2:1 (in the United States) to 6:1. 


Diagnostic Markers 


The diagnosis of encopresis is a clinical 
diagnosis based on history and physical 
examination and 
generally does not 
require any diagnostic testing. Detection of a rectal 
fecal 
impaction by digital 
rectal 
examination would support 
the diagnosis of encopresis, with constipation and overflow 
incontinence. Although not 
indicated for the diagnosis of encopresis, an abdominal 
radiograph 
demonstrating a fecal 
impaction would also support 
the diagnosis of encopresis, with 
constipation and overflow incontinence. Colonic transit 
testing, which typically involves 
ingestion of radiopaque markers followed by abdominal 
imaging to evaluate colonic transit 
time, 
can help differentiate between encopresis with or without 
constipation and overflow 
incontinence. Abdominal 
imaging demonstrating retention of radiopaque markers would suggest 
encopresis, with constipation and overflow incontinence, while prompt 
evacuation of radiopaque 
markers would support 
the diagnosis of encopresis, without 
constipation and overflow 
incontinence. In certain children, anorectal 
manometry testing may be helpful 
for better 
understanding physiological 
factors that 
may be contributing to encopresis. Anorectal 
manometry allows for evaluation of anorectal 
function and sensation. In the child with refractory 
symptoms or signs suggesting the presence of an underlying medical 
condition leading to fecal 
incontinence, further evaluation may be indicated. Such evaluation is designed to exclude other 
medical conditions. 



Functional 
Consequences of Encopresis 


Encopresis is associated with a significant 
decrease in health-related quality of life and family 
functioning, particularly in older children. 


405 


Differential 
Diagnosis 


A diagnosis of encopresis in the presence of another medical 
condition is appropriate only if the 
mechanism 
involves constipation that 
cannot 
be explained by other medical 
conditions. Fecal 
incontinence related to other medical 
conditions (e.g., chronic diarrhea, spina bifida, anal 
stenosis) would not warrant a DSM-5 diagnosis of encopresis. 


Comorbidity 


Enuresis is often present 
in children with encopresis, particularly in children with encopresis, 
without constipation and overflow incontinence. 


Other Specified 
Elimination 
Disorder 


This category applies to 
presentations in 
which 
symptoms characteristic of 
an 
elimination 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
elimination 
disorders diagnostic class. 
The 
other specified 
elimination 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific elimination 
disorder. 
This is done 
by recording 
 other specified 
elimination 
disorder  followed 
by the 
specific reason 
(e.g., 
 lowfrequency 
enuresis ). 


Coding 
note: 
Code 
N39.498 
for other specified 
elimination 
disorder with 
urinary 
symptoms; 
R15.9 
for other specified 
elimination 
disorder with 
fecal symptoms. 


Unspecified 
Elimination 
Disorder 


This category applies to 
presentations in 
which 
symptoms characteristic of 
an 
elimination 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
elimination 
disorders diagnostic class. 
The 
unspecified 
elimination 
disorder category is used 
in 
situations in 
which 
the 



clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific 
elimination 
disorder and 
includes presentations in 
which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room settings). 


Coding 
note: 
Code 
R32 
for unspecified 
elimination 
disorder with 
urinary symptoms; 
R15.9 
for unspecified 
elimination 
disorder with 
fecal symptoms. 


406 



407 



Sleep-Wake Disorders 


The DSM-5 classification 
of sleep-wake disorders is intended for use by mental 
health and general 
medical 
clinicians (those caring for adult, geriatric, and pediatric individuals). 
Sleep-wake disorders encompass 10 disorders or disorder groups: 
insomnia disorder, 
hypersomnolence disorder, narcolepsy, breathing-related sleep disorders, circadian rhythm 
sleep-
wake disorders, non rapid eye movement 
(NREM) sleep arousal 
disorders, nightmare disorder, 
rapid eye movement 
(REM) sleep behavior disorder, restless legs syndrome, and 
substance/medication-induced sleep disorder. Individuals with these disorders typically present 
with sleep-wake complaints of dissatisfaction regarding the quality, timing, and amount 
of sleep. 
Resulting daytime distress and impairment 
are core features shared by all 
of these sleep-wake 
disorders. 


The organization of this chapter is designed to facilitate differential 
diagnosis of sleep-wake 
complaints and to clarify when referral 
to a sleep specialist 
is appropriate for further assessment 
and treatment 
planning. The DSM-5 sleep disorders nosology uses a simple, clinically useful 
approach, while also reflecting scientific advances in epidemiology, genetics, pathophysiology, 
assessment, and interventions research since DSM-IV. The approach taken to the classification 
of sleep-wake disorders in DSM-5 can be understood within the context 
of  lumping versus 
splitting.  For example, in some categories (e.g., insomnia disorder), a  lumping  approach has 
been adopted (i.e., three categories that 
were separate in DSM-IV insomnia with other mental 
disorders, insomnia with other medical 
conditions, and insomnia with other sleep disorders are 
all 
included in the single insomnia category as specifiers), whereas in other categories (e.g., 
narcolepsy), a  splitting  approach has been taken (i.e., there are four separately coded subtypes 
of narcolepsy, such as type 1 with cataplexy or hypocretin deficiency, and type 2 without 
cataplexy and either without 
hypocretin deficiency or hypocretin unmeasured), reflecting the 
availability of validators derived from 
epidemiological, neurobiological, and interventions 
research. 


Because DSM-5 is intended for use by mental 
health and general 
medical 
clinicians who are 
not 
experts in sleep medicine, DSM-5 presents an effort 
to simplify sleep-wake disorders 
classification and thus aggregates diagnoses under broader, less differentiated labels. In contrast, 
the International 
Classification of 
Sleep Disorders, 3rd Edition (ICSD-3), elaborates numerous 
diagnostic subtypes, reflects the science and opinions of the sleep specialist 
community, and has 
been prepared by and for sleep specialists. 


The simpler, less-differentiated approach to the diagnosis of sleep-wake disorders in DSM-5 
shows superior interrater reliability, as well 
as convergent, discriminant, and face validity. The 
text 
accompanying each set 
of diagnostic criteria provides linkages to the corresponding 
disorders included in ICSD-3. 


The field of sleep disorders medicine has progressed in this direction since the publication of 
DSM-IV. The use of biological 
validators is now embodied in the DSM-5 classification of sleep



wake disorders, particularly for disorders of excessive sleepiness, such as narcolepsy, for which 
cerebrospinal fluid hypocretin-1 immunoreactivity values can be diagnostic; for breathing-related 
sleep disorders, for which formal 
sleep studies (i.e., polysomnography) are indicated; 
and for 
restless legs syndrome, which can often coexist 
with periodic limb movements during sleep, 
detectable via polysomnography. 


408 


Co-Occurring Disorders and Differential Diagnosis 


Sleep disorders are often accompanied by depression, anxiety, and cognitive changes that 
must 
be addressed in treatment 
planning and management. Furthermore, persistent 
sleep disturbances 
(both insomnia and excessive sleepiness) are established risk factors for the subsequent 
development 
of mental 
illnesses (including substance use and non substance use disorders) and 
other medical 
conditions. They may also represent 
a prodromal 
expression of an episode of 
mental 
illness, allowing the possibility of early intervention to preempt 
or to attenuate a full-
blown episode. 


The differential 
diagnosis of sleep-wake complaints necessitates a multidimensional 
approach, with consideration of possibly coexisting clinical 
conditions, which are the rule and 
not 
the exception. Sleep disturbances furnish a clinically useful 
indicator of clinical 
conditions 
that 
often coexist 
with depression and other common mental 
disorders. Prominent 
among these 
comorbidities are breathing-related sleep disorders, cardiac and pulmonary conditions (e.g., 
congestive heart 
failure, chronic obstructive pulmonary disease), neurodegenerative disorders 
(e.g., Alzheimer s disease), and disorders of the musculoskeletal 
system 
(e.g., osteoarthritis). 
These disorders not 
only may disturb sleep but 
also may themselves be worsened during sleep 
(e.g., prolonged apneas or electrocardiographic arrhythmias during REM sleep; 
confusional 
arousals in individuals with major neurocognitive disorder; 
seizures in individuals with complex 
partial 
seizures). REM sleep behavior disorder is often an early indicator of neurodegenerative 
disorders (alpha synucleinopathies) like Parkinson s disease. For all 
of these reasons related to 
differential 
diagnosis, clinical 
comorbidity, and facilitation of treatment 
planning sleep 
disorders are included in DSM-5. 


Key Concepts and Terms 


Four distinct 
sleep stages can be measured by polysomnography: 
REM sleep and three stages of 
NREM sleep (N1, N2, and N3). 



REM sleep, during which the majority of typical story-like dreams occur, occupies about 20% 25% of total sleep. 
NREM sleep stage 1 (N1) 
is a transition from 
wakefulness to sleep and occupies about 
5% 
of 
time spent 
asleep in healthy 
adults. 
NREM sleep stage 2 (N2), which is characterized by specific electroencephalographic waveforms (sleep spindles and K 
complexes), occupies about 50% of time spent asleep. 
NREM sleep stage 3 (N3) 
(also known as slow-wave sleep) 
is the deepest 
level 
of 
sleep and occupies about 
20% 
of 
sleep 
time in healthy, younger adults. 

These sleep stages have a characteristic temporal 
organization across the night. N3 tends to occur 
in the first 
one-third to one-half of the night 
and increases in duration in response to sleep 
deprivation. REM sleep occurs cyclically throughout 
the night, alternating with NREM sleep 
about every 80 100 minutes. REM sleep periods increase in duration toward the morning. 


Human sleep also varies characteristically across the life span. After relative stability with 
large amounts of slow-wave sleep in childhood and early adolescence, sleep continuity and depth 
deteriorate across the adult 
age range. This deterioration is reflected by increased wakefulness 
and N1 sleep and decreased N3 sleep. Because of this, age must 
be considered in the diagnosis of 
a sleep disorder in any individual. 


Polysomnography is the monitoring of multiple electrophysiological 
parameters during sleep. 
Most 
polysomnographic studies are conducted during the individual s usual 
sleeping hours that 
is, at 
night. However, daytime polysomnographic studies also are used to quantify daytime 
sleepiness. The most common daytime procedure is the multiple sleep 


409 


latency test, in which the individual 
is instructed to lie down in a dark room 
and not 
resist 
falling asleep; 
this protocol 
is repeated five times during the day. The amount 
of time required to 
fall 
asleep (sleep latency) is measured on each trial 
and is used as an index of physiological 
sleepiness. 


The following standard terminology for polysomnographic measures is used throughout 
the 
text in this chapter, and other terms provide context for the chapter discussion: 



Sleep continuity 
refers to the overall 
balance of 
sleep and wakefulness during a night 
of 
sleep.  Better  sleep continuity 
indicates consolidated sleep with little wakefulness or 
fragmentation; 
 worse  sleep continuity indicates disrupted sleep with 
more wakefulness and fragmentation. 
Specific sleep continuity measures include sleep latency the amount 
of time required to 
fall 
asleep (expressed in minutes); 
wake after sleep onset the amount 
of awake time 
between initial 
sleep onset 
and final 
awakening (expressed in minutes); 
the number of 
awakenings; 
and sleep efficiency the ratio of actual 
time spent 
asleep to time spent 
in bed 
(expressed as a percentage, with higher numbers indicating better sleep continuity). 
Sleep architecture refers to the amount and distribution of specific sleep stages. Sleep architecture measures include absolute 
amounts of 
REM sleep and each NREM sleep stage (in minutes), relative amount 
of 
REM sleep and NREM sleep stages 
(expressed as a percentage of 
total 
sleep time), and latency between sleep onset 
and the first 
REM period (REM 
latency). 
When the latency to onset 
of 
REM sleep is < 15 minutes, the terms sleep-onset 
REM 
and sleep-onset 
REM 
period 
are 
employed. 


Association With Suicidal Thoughts or Behavior 


A review of multiple studies found that 
the symptom 
of insomnia may increase the risk for 
suicidal 
thoughts, suicidal 
behavior, and death, even after adjustment 
for depression, and that 
nightmares increase risk for suicidal 
thoughts and behavior. In one study of college students, 
31.3% of those with sleep problems had suicidal 
thoughts, and conversely, nearly all 
(82.7%) 
individuals with suicidal 
thoughts had sleep problems. A review and consensus statement 
of the 
American Academy of Sleep Medicine concluded that 
in teenagers, < 8 hours of sleep is 



associated with increased risk of self-harm, suicidal thoughts, and suicidal behavior. 


Insomnia Disorder 


Diagnostic Criteria 
F51.01 


A. 
A 
predominant 
complaint 
of 
dissatisfaction 
with 
sleep 
quantity or quality, 
associated 
with 
one 
(or more) of 
the 
following 
symptoms: 
1. 
Difficulty initiating 
sleep. 
(In 
children, 
this may manifest 
as difficulty initiating 
sleep 
without 
caregiver intervention.) 
2. 
Difficulty maintaining 
sleep, 
characterized 
by frequent 
awakenings or 
problems returning 
to 
sleep 
after awakenings. 
(In 
children, 
this may manifest 
as difficulty returning 
to 
sleep 
without 
caregiver intervention.) 
3. 
Early-morning 
awakening 
with 
inability to 
return 
to 
sleep. 
B. 
The 
sleep 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
occupational, 
educational, 
academic, 
behavioral, 
or other important 
areas 
of 
functioning. 
C. 
The 
sleep 
difficulty occurs at 
least 
3 
nights per week. 
410 


D. 
The 
sleep 
difficulty is present 
for at 
least 
3 
months. 
E. 
The 
sleep 
difficulty occurs despite 
adequate 
opportunity for sleep. 
F. 
The 
insomnia 
is not 
better explained 
by and 
does not 
occur exclusively during 
the 
course 
of 
another sleep-wake 
disorder (e.g., 
narcolepsy, 
a 
breathing-related 
sleep 
disorder, 
a 
circadian 
rhythm sleep-wake 
disorder, 
a 
parasomnia). 
G. 
The 
insomnia 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication). 
H. 
Coexisting 
mental disorders and 
medical conditions do 
not 
adequately explain 
the 
predominant 
complaint 
of 
insomnia. 
Specify 
if: 
With 
mental 
disorder, 
including 
substance 
use 
disorders 
With 
medical 
condition 
With 
another sleep 
disorder 
Coding 
note: 
The 
code 
F51.01 
applies to 
all three 
specifiers. 
Code 
also 
the 
relevant 
associated 
mental disorder, 
medical condition, 
or other sleep 
disorder 
immediately after the 
code 
for insomnia 
disorder in 
order to 
indicate 
the 
association. 


Specify 
if: 
Episodic: 
Symptoms last 
at 
least 
1 
month 
but 
less than 
3 
months. 



Persistent: 
Symptoms last 
3 
months or longer. 


Recurrent: 
Two 
(or more) episodes within 
the 
space 
of 
1 
year. 
Note: 
Acute 
and 
short-term insomnia 
(i.e., 
symptoms lasting 
less than 
3 
months but 
otherwise 
meeting 
all criteria 
with 
regard 
to 
frequency, 
intensity, 
distress, 
and/or 
impairment) should 
be 
coded 
as an 
other specified 
insomnia 
disorder. 


Note: 
The 
diagnosis of 
insomnia 
disorder is given 
whether it 
occurs as an 
independent 
condition 
or is comorbid 
with 
another mental disorder (e.g., 
major depressive 
disorder), 
medical condition 
(e.g., 
pain), 
or another sleep 
disorder (e.g., 
a 
breathing-related 
sleep 
disorder). 
For instance, 
insomnia 
may develop 
its own 
course 
with 
some 
anxiety and 
depressive 
features without 
those 
features meeting 
criteria 
for any one 
mental disorder. 
Insomnia 
may also 
manifest 
as a 
clinical feature 
of 
a 
more 
predominant 
mental disorder. 
Persistent 
insomnia 
is a 
risk factor for depression, 
anxiety disorders, 
and 
alcohol use 
disorder and 
is a 
common 
residual symptom after treatment 
for these 
conditions. 
When 
insomnia 
is comorbid 
with 
a 
mental disorder, 
treatment 
may need 
to 
target 
both 
conditions. 
Given 
these 
different 
courses, 
it 
is often 
impossible 
to 
establish 
the 
precise 
nature 
of 
the 
relationship 
between 
these 
clinical entities, 
and 
this relationship 
may 
change 
over time. 
Therefore, 
in 
the 
presence 
of 
insomnia 
and 
a 
comorbid 
disorder, 
it 
is 
not 
necessary to 
make 
a 
causal attribution 
between 
the 
two 
conditions. 
Rather, 
the 
diagnosis of 
insomnia 
disorder is made 
with 
concurrent 
specification 
of 
the 
comorbid 
conditions. 
A 
concurrent 
insomnia 
diagnosis should 
only be 
considered 
when 
the 
insomnia 
is sufficiently severe 
to 
warrant 
independent 
clinical attention; 
otherwise, 
no 
separate 
diagnosis is necessary. 


Recording Procedures 


The specifiers  with mental 
disorder, including substance use disorders ; 
 with medical 
condition ; 
and  with another sleep disorder  are available to allow the clinician to note 
clinically relevant 
comorbidities. In such cases, record F51.01 insomnia disorder, with [name of 
comorbid condition(s) or disorder(s)] followed by the diagnostic code(s) for the comorbid 
conditions or disorders (e.g., F51.01 insomnia disorder, with moderate cocaine use disorder and 
trigeminal neuralagia; F14.20 moderate cocaine use disorder; G50.0 trigeminal neuralgia). 


411 


Diagnostic Features 


The essential 
feature of insomnia disorder is dissatisfaction with sleep quantity or quality with 
complaints of difficulty initiating or maintaining sleep. The sleep complaints are accompanied by 
clinically significant 
distress or impairment 
in social, occupational, or other important 
areas of 
functioning. The sleep disturbance may occur during the course of another mental 
disorder or 
medical condition, or it may occur independently. 


Different 
manifestations of insomnia can occur at 
different 
times of the sleep period. Sleep-
onset 
insomnia 
(or initial 
insomnia) involves difficulty initiating sleep at 
bedtime. Sleep 
maintenance insomnia 
(or middle insomnia) involves frequent 
or prolonged awakenings 



throughout 
the night. Late insomnia 
involves early-morning awakening with an inability to 
return to sleep. Difficulty maintaining sleep is the most 
common single symptom 
of insomnia, 
affecting about 
60% of those with insomnia, followed by early awakening and difficulty falling 
asleep, according to a U.S. national 
sample of health care plan members. A combination of these 
symptoms is the most 
common presentation overall. The specific type of sleep complaint 
often 
varies over time. Individuals who complain of difficulty falling asleep at 
one time may later 
complain of difficulty maintaining sleep, and vice versa. Symptoms of difficulty falling asleep 
and difficulty maintaining sleep can be quantified by the individual s retrospective self-report, 
sleep diaries in which information is collected prospectively, or other methods, such as 
actigraphy or polysomnography. However, the diagnosis of insomnia disorder is based on the 
individual s subjective perception of sleep or a caretaker s report. Subjective reports from 
individuals with insomnia disorder frequently indicate longer sleep latencies, greater time awake 
during the night, and less total 
sleep time than objective (e.g. polysomnographic) data 
demonstrate. The reasons for this discrepancy are not 
well 
understood, but 
disturbances in the 
underlying neurophysiology reflective of hyperarousal 
or cortical 
activation are believed to play 
a role. 


Nonrestorative sleep, 
a complaint 
of poor sleep quality that 
does not 
leave the individual 
rested upon awakening despite adequate duration, is a common sleep complaint 
usually 
occurring in association with difficulty initiating or maintaining sleep, or less frequently in 
isolation. The precise relationship of isolated nonrestorative sleep to insomnia disorder remains 
unclear. The prevalence of isolated nonrestorative sleep has been estimated at 
about 
5% and, 
unlike insomnia complaints, is reported more commonly in younger individuals. This complaint 
can also be reported in association with another sleep disorder (e.g., breathing-related sleep 
disorder). When a complaint 
of nonrestorative sleep occurs in isolation (i.e., in the absence of 
difficulty initiating and/or maintaining sleep or other sleep-wake disorders), a diagnosis of other 
specified sleep-wake disorder is made. 


Aside from 
the frequency and duration criteria required to make the diagnosis, additional 
guidelines are useful 
to quantify insomnia severity. These quantitative guidelines, while 
arbitrary, are provided for illustrative purpose only. For instance, difficulty initiating sleep is 
defined by a subjective sleep latency > 20 30 minutes, and difficulty maintaining sleep is 
defined by a subjective time awake after sleep onset 
> 20 30 minutes. Although there is no 
standard definition of early-morning awakening, this symptom 
involves awakening at 
least 
1 
hour before the scheduled time and before total 
sleep time reaches 6  hours. It 
is essential 
to 
take into account 
not 
only the final 
awakening time but 
also the bedtime on the previous evening. 
Awakening at 
4:00 A.M. 
does not 
have the same clinical 
significance in those who go to bed at 


9:00 P.M. 
as in those who go to bed at 
11:00 P.M. Such a symptom 
may also reflect 
an age-
dependent 
decrease in the ability to sustain sleep or an age-dependent 
shift 
in the timing of the 
main sleep period. Although these quantitative criteria are frequently employed in research 
designs, they do not 
in their own right 
reliably distinguish individuals with insomnia from 
normal 
sleepers. Moreover, individuals whose presentations no longer meet 
subjective diagnostic 
criteria for insomnia disorder may continue to show objective disturbance by these parameters, 
as well as daytime impairment. 
412 



Insomnia disorder involves daytime impairments as well 
as nighttime sleep difficulties. 
These include fatigue or, less commonly, daytime sleepiness; 
the latter is more common among 
older individuals and when insomnia is comorbid with another medical 
condition (e.g., chronic 
pain) or sleep disorder (e.g., sleep apnea). Impairment 
in cognitive performance may include 
difficulties with attention, concentration and memory, and performing complex manual 
skills. 
Associated mood disturbances are typically described as irritability or mood lability and less 
commonly as depressive or anxiety symptoms. Not 
all 
individuals with nighttime sleep 
disturbances are distressed or have functional 
impairment. For example, sleep continuity is often 
interrupted in healthy older adults who nevertheless identify themselves as good sleepers. A 
diagnosis of insomnia disorder should be reserved for those individuals with significant 
daytime 
distress or impairment related to their nighttime sleep difficulties. 


Associated Features 


Insomnia is often associated with physiological 
and cognitive arousal 
and conditioning factors 
that 
interfere with sleep. A preoccupation with sleep and distress attributable to the inability to 
sleep may lead to a vicious cycle: 
the more the individual 
strives to sleep, the more frustration 
builds and further impairs sleep. Thus, excessive attention and efforts to sleep, which override 
normal 
sleep-onset 
mechanisms, may contribute to the development 
of insomnia. Individuals 
with persistent 
insomnia may also acquire maladaptive sleep habits (e.g., spending excessive 
time in bed; 
following an erratic sleep schedule; 
napping) and cognitions (e.g., fear of 
sleeplessness; 
apprehensions of daytime impairments; 
clock monitoring) during the course of the 
disorder. Engaging in such activities in an environment 
in which the individual 
has frequently 
spent 
sleepless nights may further compound the conditioned arousal 
and perpetuate sleep 
difficulties. Conversely, the individual 
may fall 
asleep more easily when not 
trying to do so. 
Some individuals also report 
better sleep when away from 
their own bedrooms and their usual 
routines. 


Insomnia may be accompanied by a variety of daytime complaints and symptoms, including 
fatigue, decreased energy, and mood disturbances. Individuals with insomnia disorder may 
appear either fatigued or haggard or, conversely, overaroused and  wired.  There may be an 
increased incidence of stress-related psychophysiological 
symptoms (e.g., tension headache, 
muscle tension or pain, gastrointestinal 
symptoms); 
however, there are no consistent 
or 
characteristic abnormalities on physical 
examination. Symptoms of anxiety or depression that 
do 
not 
meet 
criteria for a specific mental 
disorder may be present, as well 
as an excessive focus on 
the perceived effects of sleep loss on daytime functioning. 


Individuals with insomnia may have elevated scores on self-report 
psychological 
or 
personality inventories with profiles indicating mild depression and anxiety, a worrisome 
cognitive style, an emotion-focused and internalizing style of conflict 
resolution, and a somatic 
focus. Patterns of neurocognitive impairment 
among individuals with insomnia disorder are 
inconsistent, although there may be impairments in performing tasks of higher complexity and 
those requiring frequent 
changes in performance strategy. Individuals with insomnia often 
require more effort to maintain cognitive performance. 


Prevalence 


Population-based estimates vary, depending on the sample and the criteria employed, but 



indicate that, across multiple countries, about 
one-third of adults report 
insomnia symptoms, 
10% 15% experience associated daytime impairments, and 4% 22% have symptoms that 
meet 
criteria for insomnia disorder, with an average of about 
10%. Insomnia disorder is the most 
prevalent 
of all 
sleep disorders. In primary care settings cross-nationally, approximately 20%  
40% of individuals complain of significant 
insomnia symptoms. Prevalence rates for medical 
and 
psychiatric populations are significantly higher than those in the general population, 


413 


especially among individuals with mood, anxiety, and substance use disorders. Forty to fifty 
percent 
of individuals with an insomnia disorder have a comorbid mental 
disorder. Insomnia is a 
more prevalent 
complaint 
among women than among men, with a gender ratio of about 
1.3:1 in 
multinational 
samples. The gender ratio rises to 1.7:1 after age 45. The prevalence in Norway 
among older adolescents (16 18 years) is nearly double in girls compared with boys. Although 
insomnia can be a symptom 
or an independent 
disorder, it 
is most 
frequently observed as a 
comorbid condition with another medical condition or mental disorder. 


Development and Course 


The onset 
of insomnia symptoms can occur at 
any time during life, but 
the first 
episode is more 
common in young adulthood. Less frequently, insomnia begins in childhood or adolescence. In 
women, the incidence of new-onset 
insomnia increases with menopause and may persist 
even 
after other symptoms (e.g., hot 
flashes) have resolved. Insomnia may have a late-life onset, 
which is often associated with the onset of other health-related conditions. 


Insomnia can be situational, persistent, or recurrent. Situational 
or acute insomnia usually 
lasts a few days or a few weeks and is often associated with life events or rapid changes in sleep 
schedules or environment. It 
usually resolves once the initial 
precipitating event 
subsides. For 
some individuals, perhaps those more vulnerable to sleep disturbances, insomnia may persist 
long after the initial 
triggering event, possibly because of conditioning factors and heightened 
arousal. The factors that 
precipitate insomnia may differ from 
those that 
perpetuate it. For 
example, an individual 
who is bedridden with a painful 
injury and has difficulty sleeping may 
then develop negative associations for sleep. Conditioned arousal 
may then persist 
and lead to 
persistent 
insomnia. A similar course may develop in the context 
of an acute psychological 
stress 
or a mental 
disorder. For instance, insomnia that 
occurs during an episode of major depressive 
disorder can become a focus of attention, with consequent 
negative conditioning, and persist 
even after resolution of the depressive episode in at 
least 
40% 50% of individuals. In some 
cases, insomnia may also have an insidious onset without any identifiable precipitating factor. 


The course of insomnia may also be episodic, with recurrent 
episodes of sleep difficulties 
associated with the occurrence of stressful 
events. Chronicity rates range from 
45% to 75% for 
follow-ups of 1 7 years. Even when the course of the insomnia has become chronic, there is 
night-to-night 
variability in sleep patterns, with an occasional 
restful 
night s sleep interspersed 
with several 
nights of poor sleep. The characteristics of insomnia may also change over time. 
Many individuals with insomnia have a history of  light  or easily disturbed sleep prior to onset 
of more persistent sleep problems. 


Insomnia complaints are more prevalent 
among middle-age and older adults. The type of 



insomnia symptom 
changes as a function of age, with difficulties initiating sleep being more 
common among young adults and problems maintaining sleep occurring more frequently among 
middle-age and older individuals. 


Difficulties initiating and maintaining sleep can also occur in children and adolescents, but 
there are more limited data on prevalence, risk factors, and comorbidity during these 
developmental 
phases of the life span. Sleep difficulties in childhood can result 
from 
conditioning factors (e.g., a child who does not 
learn to fall 
asleep or return to sleep without 
the 
presence of a parent) or from 
the absence of consistent 
sleep schedules and bedtime routines. 
Insomnia in adolescence is often triggered or exacerbated by irregular sleep schedules, especially 
phase delay. In both children and adolescents, psychological 
and medical 
factors can contribute 
to insomnia. 


The increased prevalence of insomnia in older adults is partly explained by the higher 
incidence of physical 
health problems with aging. Changes in sleep patterns associated with the 
normal 
developmental 
process must 
be differentiated from 
those exceeding age-related changes. 
Older individuals may experience significant 
delays in sleep onset 
or frequent 
awakenings that 
are not associated with complaints or daytime consequences. Although 


414 


polysomnography is of limited value in the routine evaluation of insomnia, it 
may be more 
useful 
in the differential 
diagnosis among older adults because comorbid conditions associated 
with insomnia (e.g., sleep apnea) are more common in older individuals. 


Risk and Prognostic Factors 


While the risk and prognostic factors discussed in this section increase vulnerability to insomnia, 
sleep disturbances are more likely to occur when predisposed individuals are exposed to 
precipitating events, such as major life events (e.g., illness, separation) or less severe but 
more 
chronic daily stress. Most 
individuals resume normal 
sleep patterns after the initial 
triggering 
event 
has disappeared, but 
others perhaps those more vulnerable to insomnia continue 
experiencing persistent 
sleep difficulties. Perpetuating factors such as poor sleep habits, irregular 
sleep scheduling, and the fear of not 
sleeping feed into the insomnia problem 
and may contribute 
to a vicious cycle that may induce persistent insomnia. 


Temperamental. 
Anxiety or worry-prone personality or cognitive styles, increased arousal 
predisposition, higher stress reactivity, and tendency to repress emotions can increase 
vulnerability to insomnia. 


Environmental. 
Noise, light, or uncomfortably high or low temperature may increase 
vulnerability to insomnia. High altitude may also predispose to insomnia attributable to periodic 
breathing difficulties during sleep. 


Genetic 
and 
physiological. 
Female sex and advancing age are associated with increased 
vulnerability to insomnia. Disrupted sleep and insomnia display a familial 
disposition. Thirty-
five percent 
to seventy percent 
of those with insomnia disorder report 
one or more first-degree 
relatives (most 
commonly, the mother) with a history of insomnia. Heritability may be highest 
for insomnia disorder without 
comorbidities. The prevalence of insomnia is higher among 
monozygotic twins relative to dizygotic twins; 
it 
is also higher in first-degree family members 



compared with the general 
population. The extent 
to which this link is inherited through a 
genetic predisposition, learned by observations of parental 
models, or established as a by-product 
of another psychopathology remains undetermined, although sleep reactivity to stress appears to 
play some role. 


Course 
modifiers. 
Deleterious course modifiers include poor sleep hygiene practices (e.g., 
excessive caffeine use, irregular sleep schedules). 


Culture-Related Diagnostic Issues 


Insomnia is a universal 
human experience. Identification of insomnia as a problem, the 
explanatory models for the condition, and associated help-seeking choices are affected by 
culture. Insomnia may be understood as a normal 
part 
of aging or of stress response, leading to 
low help-seeking or to coping via social 
support 
and traditional 
activities such as prayer. 
Explanatory models of insomnia vary greatly, including attributions to the effect 
of the 
environment 
(e.g., humidity) and bodily processes (e.g., poor blood circulation, internal 
heat) 
among others, and may be associated with nonbiomedical treatment-seeking. 


Sex- and Gender-Related Diagnostic Issues 


First 
onset 
in females is often associated with the birth of a new child or with menopause. 
Despite higher prevalence among perimenopausal 
and postmenopausal 
females, 
polysomnographic studies suggest 
better preservation of sleep continuity and slow-wave sleep in 
older females than in older males. 


Diagnostic Markers 


Polysomnography usually shows impairments of sleep continuity (e.g., increased sleep latency 
and time awake after sleep onset and decreased sleep efficiency [percentage of time 


415 


in bed asleep]) and may show increased stage 1 sleep and decreased stage 3 sleep. The severity 
of these sleep impairments does not 
always match the individual s clinical 
presentation or 
subjective complaint 
of poor sleep, as individuals with insomnia often underestimate sleep 
duration and overestimate wakefulness relative to polysomnography. Quantitative 
electroencephalographic analyses may indicate that 
individuals with insomnia have greater high-
frequency electroencephalography power relative to good sleepers both around the sleep-onset 
period and during non rapid eye movement 
sleep, although findings vary according to age and 
gender. This feature is consistent 
with increased cortical 
arousal. Neuroimaging studies have 
suggested altered regional 
brain function consistent 
with hyperarousal 
in insomnia, although 
interpretation of these findings is complex. Individuals with insomnia disorder may have a lower 
sleep propensity and typically do not 
show increased daytime sleepiness on objective sleep 
laboratory measures compared with individuals without sleep disorders. 


Other laboratory measures show evidence, although not 
consistently, of increased arousal 
and a generalized activation of the hypothalamic-pituitary-adrenal 
axis (e.g., increased cortisol 
levels, heart 
rate variability, reactivity to stress, increased metabolic rate). In general, findings 
are consistent 
with the hypothesis that 
increased physiological 
and cognitive arousal 
plays a 



significant role in insomnia disorder. 


Association With Suicidal 
Thoughts or Behavior 


The symptom 
of insomnia has been identified as an independent 
risk factor for suicidal 
thoughts 
and behavior. 


Functional 
Consequences of Insomnia Disorder 


Interpersonal, social, and occupational 
problems may develop as a result 
of insomnia or 
excessive concern with sleep, increased daytime irritability, and poor concentration. Decreased 
attention and concentration are common and may be related to higher rates of accidents observed 
in individuals with insomnia. Persistent 
insomnia is also associated with long-term 
consequences, including twofold or greater increased risk of new-onset 
major depressive 
disorder, anxiety disorders, and substance use disorders. Insomnia symptoms may also be a risk 
factor for relapse of major depressive disorder. Insomnia disorder, especially with objectively 
demonstrated short-sleep duration (< 6 hours), is a significant 
risk factor for numerous 
cardiovascular diseases, including hypertension, coronary artery disease/myocardial 
infarction, 
congestive heart 
failure, and cerebrovascular disease. Increased absenteeism 
and reduced 
productivity at 
work, reduced quality of life, and increased economic burden are also significant 
functional consequences of insomnia disorder. 


Differential 
Diagnosis 


Normal 
sleep 
variations. 
Normal 
sleep duration varies considerably across persons. Some 
individuals who require little sleep ( short 
sleepers ) may be concerned about 
their sleep 
duration. Short 
sleepers differ from 
individuals with insomnia disorder by the lack of difficulty 
falling or staying asleep and by the absence of characteristic daytime symptoms (e.g., fatigue, 
concentration problems, irritability). However, some short 
sleepers may desire or attempt 
to 
sleep for a longer period of time and, by prolonging time in bed, may create an insomnia-like 
sleep pattern. Clinical 
insomnia also should be distinguished from 
normal, age-related sleep 
changes. Insomnia must 
also be distinguished from 
sleep deprivation attributable to inadequate 
opportunity or circumstance for sleep resulting, for example, from 
an emergency or from 
professional or family obligations forcing the individual to stay awake. 


Situational/acute 
insomnia. 
Situational/acute insomnia 
is a condition lasting a few days to several 
weeks, often associated with acute stress due to life events or with changes in 


416 


sleep schedules. These acute or short-term 
insomnia symptoms may also produce significant 
distress and interfere with social, personal, and occupational 
functioning. When such symptoms 
are frequent 
enough and meet 
all 
other criteria except 
for the 3-month duration, a diagnosis of 
other specified insomnia disorder or unspecified insomnia disorder is made. While the disorder 
often remits with subsidence of the stress or adjustment 
to the change in sleep schedule, some 
individuals will 
develop maladaptive patterns of thought 
and behavior that 
result 
in the 
development of a chronic insomnia disorder. 



Delayed 
sleep 
phase 
and 
shift 
work 
types 
of 
circadian 
rhythm sleep-wake 
disorder. 


Individuals with the 
delayed sleep phase type of circadian rhythm 
sleep-wake disorder report 
sleep-onset 
insomnia 
only when they try to sleep at 
socially normal 
times, but 
they do not 
report 
difficulty falling 
asleep or staying asleep when their bed and rising times are delayed and coincide with their 
endogenous circadian rhythm. This pattern is observed particularly among adolescents and 
younger adults. Shift 
work type differs from 
insomnia disorder by the history of recent 
shift 
work. 


Restless 
legs 
syndrome. 
Restless legs syndrome often produces difficulties initiating and 
maintaining sleep. However, an urge to move the legs and any accompanying unpleasant 
leg 
sensations are features that differentiate this disorder from insomnia disorder. 


Breathing-related 
sleep 
disorders. 
Most 
individuals with a breathing-related sleep disorder have a 
history of loud snoring, breathing pauses during sleep, and excessive daytime sleepiness. 
Nonetheless, as many as 50% of individuals with sleep apnea may also report 
insomnia 
symptoms, a feature that is more common among women and older adults. 


Narcolepsy. 
Narcolepsy may cause insomnia complaints but 
is distinguished from 
insomnia 
disorder by the predominance of symptoms of excessive daytime sleepiness, cataplexy, sleep 
paralysis, and sleep-related hallucinations. 


Parasomnias. 
Parasomnias are characterized by a complaint 
of unusual 
behavior or events during 
sleep that may lead to intermittent awakenings and difficulty resuming sleep. However, it is these 
behavioral events, rather than the insomnia per se, that dominate the clinical picture. 
Substance/medication-induced 
sleep 
disorder, 
insomnia 
type. 
Substance/medication-induced sleep 


disorder, insomnia type, is distinguished from 
insomnia disorder 
by the fact 
that 
a substance (i.e., 
a drug of abuse, a medication, or exposure to a toxin) is judged to be etiologically related to the 
insomnia (see  Substance/Medication-Induced Sleep Disorder  later in this chapter). For 
example, insomnia occurring only in the context 
of heavy coffee consumption would be 
diagnosed as caffeine-induced sleep disorder, insomnia type, with onset during intoxication. 


Comorbidity 


Insomnia is a common comorbidity of many medical 
conditions, including but 
not 
limited to 
cancer, diabetes, coronary heart 
disease, chronic obstructive pulmonary disease, arthritis, 
fibromyalgia, other chronic pain conditions, degenerative brain diseases, and traumatic brain 
injury. The risk relationship appears to be bidirectional: 
insomnia increases the risk of many of 
these medical 
conditions, and medical 
problems increase the risk of insomnia. The direction of 
the relationship is not 
always clear and may change over time; 
for this reason, comorbid 
insomnia is the preferred terminology when insomnia coexists with another medical 
condition 
(or mental 
disorder). Insomnia disorder also coexists with numerous other sleep disorders. 
Approximately one in seven individuals with insomnia disorder has moderate to severe 
obstructive sleep apnea. Rates of insomnia complaints among individuals with narcolepsy are 
estimated to be about 50%. 


417 


Individuals with insomnia disorder frequently have a comorbid mental 
disorder, particularly 



bipolar, depressive, and anxiety disorders. Persistent 
insomnia represents a risk factor or an early 
symptom 
of subsequent 
bipolar, depressive, anxiety, and substance use disorders. Individuals 
with insomnia may misuse medications or alcohol 
to help with nighttime sleep, anxiolytics to 
combat 
tension or anxiety, and caffeine or other stimulants to combat 
excessive daytime fatigue. 
In addition to worsening the insomnia, this type of substance use may in some cases progress to a 
substance use disorder. 


Relationship to International 
Classification of Sleep Disorders 


The International 
Classification of 
Sleep Disorders, 
3rd Edition (ICSD-3), recognizes three 
insomnia diagnoses: 
chronic insomnia disorder, short-term insomnia disorder, and other 
insomnia disorder. DSM-5 insomnia disorder and ICSD-3 chronic insomnia disorder closely 
parallel 
each other with respect 
to symptom, duration, and frequency criteria; 
however, unlike 
DSM-5, ICSD-3 does not 
include a separate designation for substance/medication-induced sleep 
disorder, insomnia type. 


Hypersomnolence Disorder 


Diagnostic Criteria 
F51.11 


A. 
Self-reported 
excessive 
sleepiness (hypersomnolence) despite 
a 
main 
sleep 
period 
lasting 
at 
least 
7 
hours, 
with 
at 
least 
one 
of 
the 
following 
symptoms: 
1. 
Recurrent 
periods of 
sleep 
or lapses into 
sleep 
within 
the 
same 
day. 
2. 
A 
prolonged 
main 
sleep 
episode 
of 
more 
than 
9 
hours per day that 
is 
nonrestorative 
(i.e., 
unrefreshing). 
3. 
Difficulty being 
fully awake 
after abrupt 
awakening. 
B. 
The 
hypersomnolence 
occurs at 
least 
three 
times per week, 
for at 
least 
3 
months. 
C. 
The 
hypersomnolence 
is accompanied 
by significant 
distress or impairment 
in 
cognitive, 
social, 
occupational, 
or other important 
areas of 
functioning. 
D. 
The 
hypersomnolence 
is not 
better explained 
by and 
does not 
occur exclusively 
during 
the 
course 
of 
another sleep 
disorder (e.g., 
narcolepsy, 
breathing-related 
sleep 
disorder, 
circadian 
rhythm sleep-wake 
disorder, 
or a 
parasomnia). 
E. 
The 
hypersomnolence 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication). 
F. 
Coexisting 
mental and 
medical disorders do 
not 
adequately explain 
the 
predominant 
complaint 
of 
hypersomnolence. 
Specify 
if: 
With 
mental 
disorder, 
including 
substance 
use 
disorders 
With 
medical 
condition 
With 
another sleep 
disorder 



Coding 
note: 
The 
code 
F51.11 
applies to 
all three 
specifiers. 
Code 
also 
the 
relevant 
associated 
mental disorder, 
medical condition, 
or other sleep 
disorder 
immediately after the 
code 
for hypersomnolence 
disorder in 
order to 
indicate 
the 
association. 


Specify 
if: 
Acute: 
Duration 
of 
less than 
1 
month. 
Subacute: 
Duration 
of 
1 3 
months. 
Persistent: 
Duration 
of 
more 
than 
3 
months. 


418 


Specify 
current 
severity: 
Specify severity based 
on 
degree 
of 
difficulty maintaining 
daytime 
alertness as 
manifested 
by the 
occurrence 
of 
multiple 
attacks of 
irresistible 
sleepiness within 
any 
given 
day occurring, 
for example, 
while 
sedentary, 
driving, 
visiting 
with 
friends, 
or 


working. 
Mild: 
Difficulty maintaining 
daytime 
alertness 1 2 
days/week. 
Moderate: 
Difficulty maintaining 
daytime 
alertness 3 4 
days/week. 
Severe: 
Difficulty maintaining 
daytime 
alertness 5 7 
days/week. 


Recording Procedures 


The specifiers  with mental 
disorder, including substance use disorders ; 
 with medical 
condition ; 
and  with another sleep disorder  are available to allow the clinician to note 
clinically relevant 
comorbidities. In such cases, record F51.11 hypersomnolence disorder, with 
[name of comorbid condition(s) or disorder(s)] followed by the diagnostic code(s) for the 
comorbid conditions or disorders (e.g., F51.11 hypersomnolence disorder, with major depressive 
disorder; F33.1 major depressive disorder, recurrent, moderate). 


Diagnostic Features 


Hypersomnolence disorder includes symptoms of excessive quantity of sleep (e.g., extended 
nocturnal 
sleep or long naps), sleepiness, and sleep inertia 
(i.e., a period of impaired 
performance and reduced vigilance following awakening from 
the regular sleep episode or from 
a nap) (Criterion A). Individuals with this disorder generally fall 
asleep quickly and have a good 
sleep efficiency (> 90%). Individuals typically feel 
sleepiness developing over a period of time, 
rather than experiencing a sudden sleep  attack.  Unintentional 
sleep episodes typically occur in 
sedentary situations (e.g., while attending lectures, reading, watching television, or driving long 
distances), but 
in more severe cases they can manifest 
in high-attention situations such as at 
work, in meetings, or at 
social 
gatherings. The persistent 
need for sleep can lead to automatic 
behavior (usually of a very routine, low-complexity type) that 
the individual 
carries out 
with 
little or no subsequent 
recall. For example, individuals may find themselves having driven 
several 
miles from 
where they thought 
they were, unaware of the  automatic  driving they did in 
the preceding minutes. 



About 
40% of individuals with hypersomnolence disorder may have sleep inertia (also 
referred to as  sleep drunkenness ), and this symptom 
may help differentiate hypersomnolence 
disorder from 
other causes of sleepiness. They may have difficulty waking up in the morning, 
sometimes appearing confused, combative, or ataxic. Individuals may set 
multiple alarm 
clocks 
or rely on others to help get 
them 
out 
of bed. Sleep inertia can also occur upon awakening from 
a 
daytime nap. During that 
period, the individual 
appears awake, but 
motor coordination is 
impaired, behavior may be inappropriate, and memory deficits, disorientation in time and space, 
and feelings of grogginess may occur. This period may last some minutes to hours. 


For some individuals with hypersomnolence disorder, the major sleep episode (for most 
individuals, nocturnal 
sleep) has a duration of 9 hours or more. In the most 
extreme cases, sleep 
episodes can last 
up to 20 hours. However, the sleep is often nonrestorative and is followed by 
difficulty awakening in the morning. For other individuals with hypersomnolence disorder, the 
major sleep episode is of normal 
nocturnal 
sleep duration (7 9 hours), and they take relatively 
long daytime naps (> 1 hour) that 
do not 
improve alertness. Most 
individuals with 
hypersomnolence disorder take daytime naps nearly every day regardless of the nocturnal 
sleep 
duration. While many individuals with hypersomnolence are able to reduce their sleep time 
during working days, weekend and holiday sleep is greatly increased (by up to 3 hours). 


419 


Associated Features 


Approximately 80% of individuals with hypersomnolence disorder report 
that 
their sleep is 
nonrestorative, but 
this symptom 
is nonspecific and can occur with disorders that 
disrupt 
sleep, 
such as obstructive sleep apnea. Naps are often long (> 1 hour) and unrefreshing. Short 
naps (i.e., 
duration of < 30 minutes) are often unrefreshing. Individuals with hypersomnolence often appear 
sleepy and may even fall asleep in the clinician s waiting area. 


A subset 
of individuals with hypersomnolence disorder have a family history of 
hypersomnolence and also have symptoms of autonomic nervous system 
dysfunction, including 
recurrent 
vascular-type headaches, reactivity of the peripheral 
vascular system 
(Raynaud s 
phenomenon), and fainting. 


Prevalence 


Approximately 5% 10% of individuals in the United States who consult 
in sleep disorder clinics 
with complaints of daytime sleepiness are diagnosed as having hypersomnolence disorder. It 
is 
estimated that 
about 
1% of the European and U.S. general 
population has episodes of sleep 
inertia. Hypersomnolence occurs with relatively equal frequency in men and women. 


Development and Course 


Hypersomnolence disorder usually begins in late adolescence or early adulthood, with a mean 
age at 
onset 
of 17 24 years and a gradual 
progression over weeks to months. Little is known of 
the natural 
history, but 
for most 
individuals, the symptoms are persistent 
and stable, unless 
treatment 
is initiated. Spontaneous remission occurs in about 
11% 25% of individuals after 5 7 
years. Individuals with hypersomnolence disorder are diagnosed, on average, 10 15 years after 
the appearance of the first 
symptoms. Pediatric cases are rare. The development 
of other sleep 



disorders (e.g., breathing-related sleep disorder) may worsen the degree of sleepiness. 


Risk and Prognostic Factors 


Environmental. 
Hypersomnolence can be increased temporarily by psychological 
stress and 
alcohol 
use, but 
they have not 
been documented as environmental 
precipitating factors. Viral 
infections have been reported to have preceded or accompanied hypersomnolence in about 
10% 
of cases. Hypersomnolence is common in the months after traumatic brain injury. 


Genetic 
and 
physiological. 
Hypersomnolence may be familial, with an autosomal-dominant 
mode 
of inheritance. 


Diagnostic Markers 


Nocturnal 
polysomnography demonstrates a normal 
to prolonged sleep duration, short 
sleep 
latency, and normal 
to increased sleep continuity. The nocturnal 
distribution of rapid eye 
movement 
(REM) sleep is also normal. Sleep efficiency is typically > 90%. The multiple sleep 
latency test 
documents sleep tendency, typically indicated by mean sleep latency values of < 8 
minutes. In hypersomnolence disorder, the mean sleep latency is typically < 10 minutes and 
frequently 8 minutes or less. Sleep-onset 
REM periods (i.e., the occurrence of REM sleep within 
20 minutes of sleep onset) may be present 
but 
occur infrequently. Unfortunately, the multiple 
sleep latency test 
has poor test-retest 
reliability, and it 
does not 
distinguish well 
between 
hypersomnolence disorder and narcolepsy type 2. 


420 


A 2-week sleep diary can help document 
amounts and timing of sleep, and actigraphy 
provides more accurate data on habitual 
sleep patterns. In a 32-hour bed rest 
protocol 
in which 
subjects were encouraged to sleep ad lib, individuals with hypersomnolence disorder slept 
> 4 
hours more than control subjects. 


Functional 
Consequences of Hypersomnolence Disorder 


The low level 
of alertness that 
occurs while an individual 
fights the need for sleep can lead to 
reduced efficiency, diminished concentration, and poor memory during daytime activities. 
Hypersomnolence can lead to significant 
distress and dysfunction in work and social 
relationships. Prolonged nocturnal 
sleep and difficulty awakening can result 
in difficulty in 
meeting morning obligations, such as arriving at 
work on time. Unintentional 
daytime sleep 
episodes can be embarrassing and even dangerous, if, for instance, the individual 
is driving or 
operating machinery when the episode occurs. 


Differential 
Diagnosis 


Normative 
variation 
in 
sleep. 
 Normal  sleep duration varies considerably in the general 
population.  Long sleepers  (i.e., persons who require a greater than average amount 
of sleep) do 
not 
have excessive sleepiness, sleep inertia, or automatic behavior when they obtain their 
required amount 
of nocturnal 
sleep. Sleep is reported to be refreshing. If social 
or occupational 
demands lead to shorter nocturnal 
sleep, daytime symptoms may appear. In hypersomnolence 



disorder, by contrast, symptoms of excessive sleepiness occur regardless of nocturnal 
sleep 
duration. 


An inadequate amount 
of nocturnal 
sleep, or behaviorally induced insufficient 
sleep 
syndrome, 
can produce symptoms of daytime sleepiness very similar to those of 
hypersomnolence disorder. An average sleep duration of fewer than 7 hours per night 
strongly 
suggests inadequate nocturnal 
sleep, yet 
in the United States, the average adult 
obtains only 6.75 
hours of sleep on typical 
weeknights. Individuals with inadequate nocturnal 
sleep typically 
 catch up  with longer sleep durations on days when they are free from 
social 
or occupational 
demands or on vacations. A diagnosis of hypersomnolence disorder should not 
be made if there 
is a question regarding the adequacy of nocturnal 
sleep duration. A diagnostic and therapeutic 
trial of sleep extension for 10 14 days can often clarify the diagnosis. 


Narcolepsy. 
As in hypersomnolence disorder, individuals with narcolepsy have chronic 
sleepiness, but 
several 
clinical 
and laboratory findings help distinguish the disorders. In contrast 
to those with hypersomnolence disorder, individuals with narcolepsy tend to sleep 7 8 hours 
each day and generally feel 
refreshed on waking in the morning. Individuals with narcolepsy 
generally feel 
more alert 
after a 15-to 20-minute nap, whereas those with hypersomnolence 
disorder tend to take longer naps, have trouble waking from 
naps, and do not 
feel 
alert 
afterward. 
Individuals with narcolepsy also have varying amounts of cataplexy, hypnagogic hallucinations, 
sleep paralysis, and fragmented nocturnal 
sleep, whereas cataplexy never occurs in 
hypersomnolence disorder and the other symptoms are uncommon. The multiple sleep latency 
test typically shows more than two sleep-onset REM periods in narcolepsy. 
Fatigue 
as 
a 
symptom of 
another mental 
disorder or medical 
condition. 
Hypersomnolence disorder 


should be distinguished from 
tiredness related to fatigue that 
may be a symptom 
of another 
mental 
disorder (e.g., generalized anxiety disorder) or medical 
condition (e.g., chronic fatigue 
syndrome). Unlike hypersomnolence, tiredness is not 
necessarily relieved by increased sleep and 
is unrelated to sleep quantity or quality. 


421 


Breathing-related 
sleep 
disorders. 
Chronic sleepiness is common in breathing-related sleep 
disorders. Individuals with hypersomnolence and breathing-related sleep disorders may have 
similar patterns of excessive sleepiness. Breathing-related sleep disorders are suggested by a 
history of loud snoring, pauses in breathing during sleep, and nonrefreshing sleep. Examination 
often reveals obesity, a small 
airway, and large neck diameter. Hypertension is common, and 
some individuals may demonstrate signs of heart 
failure. Polysomnographic studies can confirm 
the presence of apneic events in breathing-related sleep disorder (and their absence in 
hypersomnolence disorder). 


Circadian 
rhythm sleep-wake 
disorders. 
In contrast 
to individuals with hypersomnolence disorder, 
individuals with specific subtypes of circadian rhythm 
sleep-wake disorder show specific 
temporal 
patterns of symptoms. For example, individuals with delayed sleep phase type often 
have sleep inertia and sleepiness in the morning and feel most alert in the evening and night, with 
habitually late bedtimes. In contrast, those with advanced sleep phase type become sleepy and go 
to bed early in the evening but are alert and wake easily in the early morning. 


Parasomnias. 
Parasomnias such as non REM sleep arousal disorders (sleepwalking/sleep terrors) 



or REM sleep behavior disorder rarely produce the prolonged, undisturbed nocturnal 
sleep or 
daytime sleepiness characteristic of hypersomnolence disorder. However, parasomnias such as 
nightmare disorder, which may result 
in significant 
curtailment 
of total 
sleep time, may 
conceivably manifest with daytime sleepiness. 
Hypersomnolence 
in 
other mental 
disorders 
and 
medical 
conditions. 
Hypersomnolence disorder must 


be distinguished from 
hypersomnolence occurring as a symptom 
of another mental 
disorder (e.g., 
major depressive episode, especially episodes with atypical 
features) or medical 
condition (e.g., 
certain cancers, multiple sclerosis). If the predominant 
complaint 
of excessive sleepiness is 
adequately explained by another mental 
disorder or medical 
condition, then an additional 
diagnosis of hypersomnolence disorder is not 
warranted. However, if the hypersomnolence is not 
adequately explained by a comorbid mental 
disorder or medical 
condition (e.g., the severity and 
nature of the hypersomnolence far exceed what 
would be expected with the mental 
disorder or 
medical condition), an additional diagnosis of hypersomnolence disorder is warranted. 


Comorbidity 


Many individuals with hypersomnolence disorder have symptoms of depression that 
may meet 
criteria for a depressive disorder. This presentation may be related to the psychosocial 
consequences of persistent 
increased sleep need. More than half of individuals with 
hypersomnolence disorder have attention-deficit/hyperactivity disorder symptoms. Individuals 
with hypersomnolence disorder are also at 
risk for substance-related disorders, particularly 
related to self-medication with stimulants. This general 
lack of specificity may contribute to very 
heterogeneous profiles among individuals whose symptoms meet 
the diagnostic criteria for 
hypersomnolence disorder. Neurodegenerative conditions, such as Alzheimer s disease, 
Parkinson s disease, and multiple system atrophy, may also be associated with hypersomnolence. 


Relationship to International 
Classification of Sleep Disorders 


The International 
Classification of 
Sleep Disorders, 
3rd Edition (ICSD-3), differentiates nine 
subtypes of  central 
disorders of hypersomnolence,  including disorders not 
covered in DSM 
such as Kleine-Levin syndrome (recurrent 
episodes of hypersomnia), hypersomnolence due to a 
medical/neurological condition or substance use, and insufficient sleep syndrome. 


422 


Narcolepsy 


Diagnostic Criteria 


A. 
Recurrent 
periods of 
an 
irrepressible 
need 
to 
sleep, 
lapsing 
into 
sleep, 
or 
napping 
occurring 
within 
the 
same 
day. 
These 
must 
have 
been 
occurring 
at 
least 
three 
times per week over the 
past 
3 
months. 
B. 
The 
presence 
of 
at 
least 
one 
of 
the 
following: 

1. 
Episodes of 
cataplexy, 
defined 
as either (a) or (b), 
occurring 
at 
least 
a 
few 
times per month: 
a. 
In 
individuals with 
long-standing 
disease, 
brief 
(seconds to 
minutes) 
episodes of 
sudden 
bilateral loss of 
muscle 
tone 
with 
maintained 
consciousness that 
are 
precipitated 
by laughter or joking. 
b. 
In 
children 
or in 
individuals within 
6 
months of 
onset, 
spontaneous 
grimaces or jaw-opening 
episodes with 
tongue 
thrusting 
or a 
global 
hypotonia, 
without 
any obvious emotional triggers. 
2. 
Hypocretin 
deficiency, 
as measured 
using 
cerebrospinal fluid 
(CSF) 
hypocretin-1 
immunoreactivity values (less than 
or equal to 
one-third 
of 
values obtained 
in 
healthy subjects tested 
using 
the 
same 
assay, 
or less than 
or equal to 
110 
pg/mL). 
Low CSF 
levels of 
hypocretin-1 
must 
not 
be 
observed 
in 
the 
context 
of 
acute 
brain 
injury, 
inflammation, 
or infection. 
3. 
Nocturnal sleep 
polysomnography showing 
rapid 
eye 
movement 
(REM) sleep 
latency less than 
or equal to 
15 
minutes, 
or a 
multiple 
sleep 
latency test 
showing 
a 
mean 
sleep 
latency less than 
or equal to 
8 
minutes and 
two 
or 
more 
sleep-onset 
REM periods. 
Specify 
whether: 


G47.411 
Narcolepsy 
with 
cataplexy 
or hypocretin 
deficiency 
(type 
1): 


Criterion 
B1 
(episodes of 
cataplexy) or Criterion 
B2 
(low CSF 
hypocretin-1 
levels) is met. 


G47.419 
Narcolepsy 
without cataplexy 
and 
either without hypocretin 
deficiency 
or hypocretin 
unmeasured 
(type 
2): 
Criterion 
B3 
(positive 
polysomnography/multiple 
sleep 
latency test) is met, 
but 
Criterion 
B1 
is not 
met 
(i.e., 
no 
cataplexy is present) and 
Criterion 
B2 
is not 
met 
(i.e., 
CSF 
hypocretin-1 
levels are 
not 
low or have 
not 
been 
measured). 


G47.421 
Narcolepsy 
with 
cataplexy 
or hypocretin 
deficiency 
due 
to 
a 


medical 
condition 
G47.429 
Narcolepsy 
without cataplexy 
and 
without hypocretin 
deficiency 
due 
to 
a 
medical 
condition 


Coding 
note: 
For the 
subtype 
narcolepsy with 
cataplexy or hypocretin 
deficiency 
due 
to 
a 
medical condition 
and 
the 
subtype 
narcolepsy without 
cataplexy and 
without 
hypocretin 
deficiency due 
to 
a 
medical condition, 
code 
first 
the 
underlying 
medical 
condition 
(e.g., 
G71.11 
myotonic dystrophy; 
G47.429 
narcolepsy without 
cataplexy 
and 
without 
hypocretin 
deficiency due 
to 
myotonic dystrophy). 


Specify 
current 
severity: 


Mild: 
Need 
for naps only once 
or twice 
per day. 
Sleep 
disturbance, 
if 
present, 
is 
mild. 
Cataplexy, 
when 
present, 
is infrequent 
(occurring 
less than 
once 
per week). 
Moderate: 
Need 
for multiple 
naps daily. 
Sleep 
may be 
moderately disturbed. 


Cataplexy, 
when 
present, 
occurs daily or every few days. 


423 



Severe: 
Nearly constant 
sleepiness and, 
often, 
highly disturbed 
nocturnal sleep 
(which 
may include 
excessive 
body movement 
and 
vivid 
dreams). 
Cataplexy, 
when 
present, 
is drug-resistant, 
with 
multiple 
attacks daily. 


Subtypes 


A diagnosis of narcolepsy, type 1 (NT1; 
i.e., with cataplexy or hypocretin deficiency) is most 
often based on the presence of recurrent 
sleepiness and cataplexy (given the limited use of 
cerebrospinal 
fluid [CSF] hypocretin determinations). However, cataplexy can emerge years 
following onset 
of sleepiness. Therefore, some individuals may be initially assigned a diagnosis 
of narcolepsy, type 2 (NT2; 
i.e., without 
cataplexy and either without 
hypocretin deficiency or 
with hypocretin unmeasured), based on sleepiness and positive multiple sleep latency test 
(MSLT) findings, only to be reassigned to a diagnosis of NT1 following emergence of cataplexy. 
NT1 established by demonstration of low CSF 
hypocretin levels may manifest 
without 
evidence 
of clear cataplexy. Other explanations for excessive daytime sleepiness (e.g., sleep deprivation, 
shift 
work, other sleep disorders) and episodes of sudden loss of muscle tone (e.g., seizures, falls 
of other origin, functional 
neurological 
symptom 
disorder [conversion disorder]) should be ruled 
out. NT2 is established on the basis of chronic sleepiness and characteristic nocturnal 
sleep 
polysomnography findings (e.g., short 
REM sleep latency) or MSLT 
findings showing short 
mean sleep latency and two or more sleep-onset REM periods (SOREMPs). 


NT1 and NT2 can result 
from 
other neurological, infectious, metabolic, and genetic 
conditions. Inherited disorders, tumors, and head trauma are the most 
common causes of 
secondary narcolepsy. In other cases, the destruction of hypocretin neurons may be secondary to 
trauma or hypothalamic surgery. Head trauma or infections of the central 
nervous system 
can, 
however, produce transitory decreases in CSF 
hypocretin-1 levels without 
hypocretin cell 
loss, 
complicating the diagnosis. 


Other etiologies include inflammatory lesions due to multiple sclerosis and acute 
disseminated encephalomyelitis, vascular disorders such as stroke, and encephalitis. Autosomal 
dominant 
cerebellar ataxia, deafness, and narcolepsy, or ADCA DN, is a familial 
degenerative 
disorder due to missense mutations of the DNA methyltransferase (DNMT1) gene. Cataplexy 
with some degree of sleepiness can be caused by other neurological 
conditions, including Prader-
Willi 
syndrome, Niemann-Pick disease type C, M bius syndrome, and Norrie disease. 
Hypocretin deficiency has been reported in Parkinson s disease as well. NT2-like physiology has 
been reported in myotonic dystrophy and Prader-Willi syndrome. 


Diagnostic Features 


The essential 
features of narcolepsy are recurrent 
daytime naps or lapses into sleep that 
occur 
typically daily but 
that 
must 
occur at 
a minimum 
of three times a week for at 
least 
3 months 
(Criterion A), and are accompanied by one or more of the following: 
cataplexy (Criterion B1), 
hypocretin deficiency (Criterion B2), or characteristic abnormalities on a nocturnal 
polysomnogram 
or on the MSLT 
(Criterion B3). In most 
individuals with NT1, the first 
symptom 
to manifest 
is sleepiness or increased sleep need, followed by cataplexy. Sleepiness is 
worse in sedentary circumstances and typically is relieved by brief (10 20 minutes) naps. 


NT1 generally manifests with cataplexy, typically brief episodes (seconds up to 2 minutes) of 



sudden, bilateral 
loss of muscle tone precipitated by emotions. A range of positive emotions can 
trigger cataplexy, including those associated with laughter, anticipation, or surprise. Less 
commonly, cataplexy can be triggered by negative emotions such as anger and embarrassment. 
Muscles affected include those of the neck, jaw, arms, legs, or whole body, resulting in head 
bobbing, jaw dropping, or complete falls. Individuals are awake and aware during cataplexy. 
Cataplexy should not be confused with  weakness  occurring in 


424 


the context 
of athletic activities (physiological) or exclusively after unusual 
emotional 
triggers such as stress or anxiety (suggesting possible psychopathology). 


In children and rarely in adults with acute NT1 symptom 
onset, cataplexy may manifest 
as 
continuous hypotonia rather than episodic bouts of weakness triggered by strong emotions. This 
continuous hypotonia may result 
in gait 
instability, ptosis, and slack jaw. Superimposed on this 
muscle weakness, some individuals may demonstrate phenomena such as tongue protrusion and 
grimacing. This static cataplexy is most common within 6 months of a rapid onset. 


NT1 is caused by loss of hypothalamic neurons that 
produce the hypocretin (orexin) 
neuropeptides, and CSF 
hypocretin levels are typically less than one-third of control 
values (< 
110 pg/mL 
in most 
laboratories). Individuals with cataplexy have been shown to have low CSF 
hypocretin levels in 85% 90% of cases. In contrast, most 
individuals with NT2 have normal 
or 
intermediate levels of CSF 
hypocretin. Thus, hypocretin deficiency is a sufficient 
diagnostic test 
for NT1 (Criterion B2). If CSF 
hypocretin is measured and not 
low, an NT2 diagnosis is based 
on clinical symptoms (Criterion A) and sleep study data outlined in Criterion B3. 


A nocturnal 
polysomnogram 
followed by an MSLT 
is the conventional 
method for 
confirming the diagnosis of both NT1 (if hypocretin testing is unavailable or not 
feasible) and 
NT2 (Criterion B3). These tests must 
be performed after the individual 
has stopped all 
psychotropic medications (for a duration based on elimination half-life) and obtained adequate 
sleep time on a normal 
sleep-wake schedule (as documented with sleep diaries or, preferably, 
actigraphy), ideally for 2 weeks. Notably, the abrupt 
discontinuation of antidepressants, aadrenergic 
agonist 
medications, or stimulants or use of these medications during testing can alter 
REM sleep physiology. 


The MSLT 
result 
must 
be positive for a diagnosis of NT2, showing a mean sleep latency of 
= 8 minutes plus at 
least 
two SOREMPs; 
specifically, REM sleep must 
occur in at 
least 
two of 
the five nap opportunities. Alternatively, a nocturnal 
sleep-onset 
REM period (nSOREMP; 
REM 
sleep-onset 
latency = 15 minutes) during polysomnography is sufficient 
to confirm 
the diagnosis 
and meets Criterion B3. An nSOREMP 
is highly specific to NT1 (95% 97%) but 
only 
moderately sensitive (54% 57%). False positive findings of SOREMPs can occur with shift 
work, circadian rhythm 
sleep-wake disorders, severe obstructive sleep apnea, medication effects, 
and insufficient sleep disorder. 


The nocturnal 
polysomnogram 
and MSLT 
are diagnostically limited, especially in NT2. 
While reliability of diagnostic MSLT 
testing is relatively high at 
85% 95% for NT1, reliability 
for the NT2 diagnosis is poorer. Test-retest 
reliability may be < 50%. This poor reliability may 
be due to day-to-day variability in NT2 physiology and technical 
aspects of the polysomnogram 
and MSLT 
testing, especially inadequate attention to prior sleep time/schedule and 
medication/drug use. 



Normal 
or intermediate CSF 
hypocretin levels among individuals with cataplexy symptoms 
can decline to undetectable levels over time. 


Associated Features 


When sleepiness is severe, automatic behaviors may occur, with the individual 
continuing his or 
her activities in a semiautomatic, hazelike fashion without 
memory or consciousness. 
Approximately 20% 60% of individuals experience vivid hypnagogic hallucinations before or 
upon falling asleep or hypnopompic hallucinations just 
after awakening. These hallucinations are 
typically visual 
or auditory, and sometimes tactile. They are distinct 
from 
the less vivid, 
nonhallucinatory dream-like mentation at sleep onset that occurs in persons with normal sleep. 


Approximately 20% 60% of affected individuals experience sleep paralysis upon falling 
asleep or awakening, leaving them 
awake but 
unable to move or speak. However, many normal 
sleepers also report occasional sleep paralysis, especially with stress or sleep 


425 


deprivation. Individuals with narcolepsy can have a range of nocturnal 
sleep symptoms, 
including disrupted nighttime sleep (frequent, brief awakenings), vivid and realistic dreams, 
periodic limb movements of sleep, and REM sleep behavior disorder. Nocturnal 
eating may 
occur. Obesity is common. Individuals may appear sleepy or fall 
asleep in the waiting area or 
during clinical 
examination. During cataplexy, individuals may slump in a chair and have slurred 
speech or drooping eyelids. If the clinician is able to check reflexes during cataplexy (most 
attacks are < 10 seconds), reflexes are abolished during whole body cataplexy an important 
finding distinguishing genuine cataplexy from 
functional 
neurological 
symptom 
disorder 
(conversion disorder). 


Although IQ testing is generally normal 
in individuals with narcolepsy, impairments in 
working memory and executive functioning have been reported. 


Prevalence 


Narcolepsy-cataplexy (NT1) affects 0.02% 0.05% of the adult 
general 
population worldwide 
and has an incidence of 0.74 per 100,000 person-years in the United States. Some prevalence 
variation has been reported, including lower rates in Israel 
and higher rates in Japan than in 
Europe and the United States. The true prevalence of NT2 is unknown in part 
because of 
diagnostic variability. Narcolepsy affects both genders fairly equally, but 
this may vary among 
different populations. 


Development and Course 


Onset 
occurs most 
often in childhood and adolescence or young adulthood but 
rarely in old age. 
Peak age at 
onset 
is around 15 25 years. Onset 
can be abrupt 
or progressive, with cataplexy 
developing over years. It 
has been reported that 
children presenting with abrupt 
onset 
of NT1 
symptoms have the highest 
disease severity but 
that 
disease severity in these cases tends to 
partially improve in the first 
few years after onset. Abrupt 
onset 
in young, prepubescent 
children 
can be associated with obesity and premature puberty. About 
50% of individuals with narcolepsy 
diagnosed in adulthood recall 
symptom 
onset 
in childhood or adolescence, highlighting problems 



of diagnostic delays for this condition. Once the disorder has manifested, the course is persistent 
and lifelong. 


In 90% of cases, the first 
symptom 
to manifest 
is sleepiness or increased sleep, followed by 
cataplexy (within 1 year in 50% of cases, within 3 years in 85%). Sleepiness, hypnagogic 
hallucinations, vivid dreaming, and REM sleep behavior disorder (vocalizations or complex 
motor behavior during REM sleep) are early symptoms. Excessive sleep rapidly progresses to an 
inability to stay awake during the day, and to maintain good sleep at 
night, without 
a clear 
increase in total 
24-hour sleep time. In the first 
months, cataplexy may be atypical, especially in 
children, manifesting with a generalized hypotonia rather than with episodic emotionally 
triggered weakness. In general, narcolepsy symptoms remain fairly stable but 
may fluctuate with 
life events such as pregnancy and stressors. Exacerbations of symptoms suggest 
lack of 
compliance with medications or development of a concurrent sleep disorder, notably sleep apnea, 
which has been identified in about a quarter of individuals with narcolepsy. 


Young children and adolescents with narcolepsy often develop aggression or behavioral 
problems secondary to sleepiness and/or nighttime sleep disruption. Workload and social 
pressure increase through high school 
and college, reducing available sleep time at 
night. 
Pregnancy does not 
seem 
to modify symptoms consistently. After retirement, individuals 
typically have more opportunity for napping, reducing the need for stimulants. Maintaining a 
regular schedule benefits individuals at all ages. 


Risk and Prognostic Factors 


Temperamental. 
Individuals with narcolepsy commonly report 
that 
they need more sleep than 
other family members. 


426 


Environmental. 
Group A streptococcal 
throat 
infection, influenza (notably pandemic H1N1 
2009), or other winter infections, as well 
as vaccinations (specifically Pandemrix H1N1 
vaccination), may trigger an autoimmune process in some individuals, producing narcolepsy a 
few months later. Head trauma and abrupt 
changes in sleep-wake patterns (e.g., job changes, 
stress) may be additional triggers. 


Genetic 
and 
physiological. 
Monozygotic twins are 25% 32% concordant 
for narcolepsy. The 
prevalence of narcolepsy is 1% 2% in first-degree relatives (a 10- to 40-fold increase overall). 
Narcolepsy is strongly associated with HLA DQB1*06:02 (see  Diagnostic Markers ). 
DQB1*03:01 increases, while DQB1*05:01, DQB1*06:01, and 
DQB1*06:03 reduce risk in the 
presence of DQB1*06:02, but 
the effect 
is small. Polymorphisms within the T-cell 
receptor alpha 
gene and other immune-modulating genes also modulate risk slightly. 


Culture-Related Diagnostic Issues 


Narcolepsy has been described in many ethnoracial 
groups and cultural 
contexts. One study of 
1,097 treatment-seeking individuals suggested that 
among African Americans, more cases may 
manifest 
without 
cataplexy or with atypical 
cataplexy (although CSF 
hypocretin is low), and 
with earlier onset 
compared with non-Latinx Whites. Diagnosis may be further complicated by 
the higher presence of obesity and obstructive sleep apnea in this population, which can be 



related to differential 
exposure to social 
determinants of health, including food insecurity, food 
deserts, and limited access to safe and affordable places for physical 
activity. Individuals with 
narcolepsy often experience sleep paralysis, which may be attributed to supernatural 
forces (e.g., 
frightening spirit 
is sitting on the sleeper s chest) in some cultural 
contexts, contributing to the 
perceived dangerousness of the condition and to help-seeking decisions. 


Diagnostic Markers 


Nocturnal 
polysomnography followed by an MSLT 
is used to confirm 
the diagnosis of 
narcolepsy, especially when the disorder is first 
being diagnosed and before treatment 
has begun. 
In the presence of clear-cut 
cataplexy, the polysomnography and MSLT 
are confirmatory for 
NT1. In the absence of cataplexy and hypocretin deficiency (if measured), the MSLT 
is 
diagnostic of NT2. Drug or medication effects (e.g., REM-inhibiting antidepressants or sedating 
medications), stimulant 
withdrawal, prior sleep deprivation, shift 
work, or severe depression may 
result 
in an inaccurate MSLT 
result 
and must 
be ruled out 
prior to performance of the MSLT. In 
particular, chronically insufficient sleep is common and must be considered. 


An nSOREMP 
is highly specific (approximately 1% positive in control 
subjects) but 
moderately sensitive (approximately 50%) for NT1. In contrast, an nSOREMP 
was only found in 
10% 23% of NT2 persons with normal 
hypocretin levels, suggesting even lower sensitivity in 
this subtype. The MSLT 
result 
is considered positive for narcolepsy if it 
displays an average 
sleep latency of = 8 minutes and SOREMPs in two or more naps on a four-or five-nap test. The 
MSLT 
result 
is positive in 90% 95% of individuals with NT1 versus 2% 4% of control 
subjects 
or individuals with other sleep disorders. As noted, poor test-retest 
reliability for NT2 precludes 
determination of comparable data for NT2. Additional 
polysomnographic findings among 
individuals with narcolepsy often include frequent 
arousals, decreased sleep efficiency, and 
increased stage 1 sleep. Periodic limb movements (found in about 
40% of individuals with NT1) 
and sleep apnea are often noted. 


Hypocretin deficiency is demonstrated by measuring CSF 
hypocretin-1 levels. The test 
is 
particularly useful 
in individuals with suspected pseudocataplexy and those without 
typical 
cataplexy, or in treatment-refractory cases. The diagnostic value of the test 
is not 
affected by 
medications, sleep deprivation, or the time of day or night 
when it 
is collected, but 
the findings 
are uninterpretable when the individual is severely ill with a concurrent 


427 


infection or head trauma or is comatose. CSF 
cytology, protein, and glucose are within 
normal 
range even when sampled within weeks of rapid onset 
of the disorder. When measured in 
individuals with typical 
cataplexy symptoms, CSF 
hypocretin-1 is often already very diminished 
or undetectable. 


About 
85% 95% of individuals 
with NT1 are positive for the HLA DQB1*06:02 haplotype. 
This gene influences immune system 
antigen presentation, supporting an underlying autoimmune 
pathophysiology of NT1. Outbreaks of NT1 after specific vaccinations and infections further 
support 
an autoimmune etiology. In contrast 
to NT1, there are no biomarkers of NT2. Only about 
40% 50% of individuals with NT2 are positive for DQB1*06:02. As 12% 38% of the general 
population is DQB1*06:02 positive, testing for this allele is not 
very helpful 
for diagnosing NT2 



but can be helpful for screening of NT1. 


Functional 
Consequences of Narcolepsy 


School 
performance, driving, work, or other activities that 
require sustained attention are 
impaired, and individuals with narcolepsy should avoid jobs that 
place themselves (e.g., working 
with machinery) or others (e.g., bus driver, pilot) in danger. Once the narcolepsy is controlled 
with therapy, individuals can usually drive, although rarely long distances alone. Untreated 
individuals are also at 
risk for social 
isolation and accidental 
injury to themselves or others. 
Social 
relations may suffer as these individuals strive to avert 
cataplexy by exerting control 
over 
emotions or stimuli that cause emotions. 


Differential 
Diagnosis 


Other hypersomnias. 
Hypersomnolence disorder (also known as idiopathic hypersomnia) and 
narcolepsy are similar with respect 
to the presence of chronic daytime sleepiness, age at 
onset 
(typically adolescence or early adulthood), and stable course over time, but 
can be distinguished 
based on distinctive clinical 
and laboratory features. Individuals with hypersomnolence disorder 
typically have longer and less disrupted nocturnal 
sleep, greater difficulty awakening, more 
persistent 
daytime sleepiness (as opposed to more discrete  sleep attacks  in narcolepsy), longer 
and less refreshing daytime sleep episodes, and little or no dreaming during daytime naps. By 
contrast, individuals with NT1 generally have cataplexy. Those with NT1 or NT2 may 
demonstrate recurrent 
intrusions of elements of REM sleep into the transition between sleep and 
wakefulness (e.g., sleep-related hallucinations and sleep paralysis). The MSLT 
typically 
demonstrates shorter sleep latencies (i.e., greater physiological 
sleepiness) as well 
as the 
presence of multiple SOREMPs in individuals with narcolepsy. 
Sleep 
deprivation 
and 
insufficient 
nocturnal 
sleep. 
Sleep deprivation and insufficient 
nocturnal 
sleep 


are common in adolescents and shift 
workers. In adolescents, difficulties falling asleep at 
night 
are common, causing sleep deprivation. The MSLT 
result 
may be falsely positive if conducted 
while the individual is sleep deprived or while his or her sleep is phase delayed. 


Sleep 
apnea 
syndromes. 
Obstructive sleep apnea is common in the general 
population and can be 
present 
in individuals with narcolepsy due to obesity. Because obstructive sleep apnea is more 
frequent 
than narcolepsy, cataplexy may be overlooked (or absent). Narcolepsy should be 
considered in individuals with persistent sleepiness despite treatment of their sleep apnea. 


Insomnia 
disorder. 
Individuals with narcolepsy may focus on the presence of nocturnal 
sleep 
disruption and incorrectly attribute daytime sleepiness to insomnia disorder. Although 
individuals with narcolepsy, like those with insomnia disorder, may experience frequent 
awakenings during the night, individuals with narcolepsy typically have no difficulty initiating 
sleep or returning to sleep in contrast to those with insomnia disorder. 


428 


Moreover, insomnia disorder is not 
typically associated with the severity of daytime sleepiness 
observed in narcolepsy. 
Major depressive 
disorder. 
Excessive daytime sleepiness is a common complaint 
of both 



individuals with major depression and individuals with narcolepsy. The presence of cataplexy 
(which is not 
a feature of major depressive disorder) along with the severity of excessive daytime 
sleepiness indicates a diagnosis of NT1 rather than major depressive disorder. Moreover, in 
individuals with major depression, MSLT 
results are most 
often normal, and there is dissociation 
between subjective and objective sleepiness, as measured by the mean sleep latency during the 
MSLT. In a meta-analysis of individuals with psychiatric disorders evaluated for sleepiness, 
while 25% had a mean sleep latency of < 8 minutes on the MSLT, only rarely were two or more 
SOREMPs noted on the MSLT, highlighting the more specific REM sleep dysfunction of 
narcolepsy. 


Functional 
neurological 
symptom disorder (conversion 
disorder; 
pseudocataplexy). 


Individuals with 
functional 
neurological 
symptom 
disorder can present 
with weakness that 
may raise questions of 
cataplexy. However, in functional 
neurological 
symptom 
disorder, the weakness is often long-
lasting, has unusual 
triggers, and can result 
in frequent 
falls. Individuals may report 
sleeping and 
dreaming during MSLT 
naps, yet 
the MSLT 
does not 
show the characteristic SOREMP. Home 
video recordings and video during sleep studies can be helpful 
to distinguish this condition from 
true cataplexy. The weakness is usually generalized in pseudocataplexy, without 
partial 
attacks. 
Full-blown, long-lasting pseudocataplexy may occur during consultation, allowing the 
examining physician enough time to verify reflexes, which remain intact. 
Attention-deficit/hyperactivity 
disorder or other behavioral 
problems. 


In children and adolescents, 
sleepiness can cause behavioral 
problems, including aggressiveness and inattention, leading to a 
misdiagnosis of attention-deficit/hyperactivity disorder (ADHD). 


Atonic 
seizures. 
Atonic seizures, a type of seizure that 
causes sudden loss of muscle strength, 
must 
be distinguished from 
cataplexy. Atonic seizures are not 
commonly triggered by emotions 
and tend to manifest 
as abrupt 
falls rather than the slower  melting  quality of cataplexy. Atonic 
seizures usually occur in individuals with additional 
seizure types and have distinct 
signatures on 
the electroencephalogram. 


Syncope. 
Like syncope, cataplexy usually develops over several 
seconds, but 
individuals with 


cataplexy do not have presyncopal symptoms of dizziness, tunnel vision, and auditory changes. 
Chorea 
and 
motor disorders. 
In young children, cataplexy can be misdiagnosed as chorea or 
pediatric autoimmune neuropsychiatric disorders associated with streptococcal 
infections 
(PANDAS), especially in the context 
of a strep throat 
infection and high antistreptolysin O 
antibody levels. Some children may have an overlapping motor disorder close to onset 
of the 
cataplexy. 


Schizophrenia. 
In the presence of florid and vivid hypnagogic hallucinations, individuals with 
narcolepsy may think these experiences are real a feature that 
suggests the presence of a true 
hallucination characteristic of schizophrenia. However, clear differences have been described in 
the pattern of hallucinatory experiences in narcolepsy compared with schizophrenia. Individuals 
with narcolepsy tend to report 
sleep-related multisensory  holistic  hallucinations (visual, 
auditory, tactile) rather than the predominantly verbal-auditory sensory mode of individuals with 
schizophrenia. Moreover, high-dose stimulant 
treatment 
of individuals with narcolepsy may 
result 
in the development 
of persecutory delusions. If cataplexy is present 
with hallucinations or 
delusions, the first 
clinical 
supposition would be that 
these symptoms are secondary to 
narcolepsy before consideration of a co-occurring diagnosis of schizophrenia. 



429 


Comorbidity 


Medical 
and psychiatric comorbidities are common among individuals with narcolepsy and 
include obesity, bruxism, enuresis, precocious puberty (among individuals with pediatric-onset 
narcolepsy), mood disorders, and ADHD. Rapid weight gain is common in young children with a 
sudden disease onset. Parasomnias (e.g., sleepwalking, REM sleep behavior disorder), 
obstructive sleep apnea, restless legs syndrome, and periodic limb movements are common in 
individuals who develop narcolepsy. Comorbid sleep apnea should be considered if there is a 
sudden aggravation of preexisting narcolepsy. 


Relationship to International 
Classification of Sleep Disorders 


The International 
Classification of 
Sleep Disorders, 
3rd Edition (ICSD-3), differentiates two 
subtypes of narcolepsy: 
NT1 (narcolepsy with cataplexy or hypocretin deficiency) and NT2 
(narcolepsy without 
cataplexy or hypocretin deficiency). NT1 secondary to another medical 
condition (G47.421) and NT2 secondary to another medical 
condition (G47.429) are reported in 
ICSD-3 as secondary narcolepsy subtypes. 


Breathing-Related Sleep Disorders 


The breathing-related sleep disorders category encompasses three relatively distinct 
disorders: 
obstructive sleep apnea hypopnea, central sleep apnea, and sleep-related hypoventilation. 


Obstructive Sleep 
Apnea Hypopnea 


Diagnostic Criteria 
G47.33 


A. 
Either (1) or (2): 


1. 
Evidence 
by polysomnography of 
at 
least 
five 
obstructive 
apneas or 
hypopneas per hour of 
sleep 
and 
either of 
the 
following 
sleep 
symptoms: 
a. 
Nocturnal breathing 
disturbances: 
snoring, 
snorting/gasping, 
or breathing 
pauses during 
sleep. 
b. 
Daytime 
sleepiness, 
fatigue, 
or unrefreshing 
sleep 
despite 
sufficient 
opportunities to 
sleep 
that 
is not 
better explained 
by another mental 
disorder (including 
a 
sleep 
disorder) and 
is not 
attributable 
to 
another 
medical condition. 
2. 
Evidence 
by polysomnography of 
15 
or more 
obstructive 
apneas and/or 
hypopneas per hour of 
sleep 
regardless of 
accompanying 
symptoms. 
Specify 
current 
severity: 
Mild: 
Apnea 
hypopnea 
index is less than 
15. 



Moderate: 
Apnea 
hypopnea 
index is 15 30. 
Severe: 
Apnea 
hypopnea 
index is greater than 
30. 


Specifiers 


Disease severity is measured by a count 
of the number of apneas plus hypopneas per hour of 
sleep (apnea hypopnea index) using polysomnography or other overnight monitoring. 


430 


Apnea 
refers to the total 
absence of airflow, and hypopnea 
refers to a reduction in airflow. 
Overall 
severity is also informed by levels of nocturnal 
desaturation and sleep fragmentation 
(measured by brain cortical 
arousal 
frequency and sleep stages) and degree of associated 
symptoms and daytime impairment. However, the exact 
number and thresholds may vary 
according to the specific measurement 
techniques used, and these numbers may change over 
time. Regardless of the apnea hypopnea index (count) per se, the disorder is considered to be 
more severe when apneas and hypopneas are accompanied by significant 
oxygen hemoglobin 
desaturation (e.g., when more than 10% of the sleep time is spent 
at 
desaturation levels of < 
90%) or when sleep is severely fragmented as shown by an elevated arousal 
index (arousals per 
hour of sleep > 30) or reduced time in deep sleep (e.g., percentage stage N3 [slow-wave sleep] < 
5%). 


Diagnostic Features 


Obstructive sleep apnea hypopnea is the most 
common breathing-related sleep disorder. It 
is 
characterized by repeated episodes of upper (pharyngeal) airway obstruction (apneas and 
hypopneas) during sleep. Each apnea or hypopnea represents a reduction in breathing of at 
least 
10 seconds in duration in adults or two missed breaths in children and is typically associated with 
drops in oxygen saturation of = 3% and/or an electroencephalographic arousal. Both sleep-
related (nocturnal) and wake-time symptoms are common. The cardinal 
symptoms of obstructive 
sleep apnea hypopnea are snoring and daytime sleepiness. 


Obstructive sleep apnea hypopnea in adults is diagnosed on the basis of findings from 
a 
polysomnogram 
(or sleep testing performed outside of the sleep center, referred to as out 
of 
center sleep testing 
[OCST]) and symptoms. The diagnosis is based on symptoms of 1) nocturnal 
breathing disturbances (i.e., snoring, snorting/gasping, breathing pauses during sleep), or 2) 
daytime sleepiness, fatigue, or unrefreshing sleep despite sufficient 
opportunities to sleep that 
are 
not 
better explained by another mental 
disorder and not 
attributable to another medical 
condition, 
along with 3) evidence by polysomnography (or OCST) of five or more obstructive apneas or 
hypopneas per hour of sleep (Criterion A1). Diagnosis can be made in the absence of these 
symptoms if there is evidence by polysomnography (or limited OCST) of 15 or more obstructive 
apneas and/or hypopneas per hour of sleep (Criterion A2). 


Criteria for a diagnosis of obstructive sleep apnea hypopnea in children differ from 
those for 
a diagnosis in adults. An obstructive apnea hypopnea index of one or more events per hour or 
evidence of obstructive hypoventilation in association with snoring or polysomnographic 
evidence of airflow obstruction is used to define thresholds of abnormality in children. 



Polysomnographic findings in children may differ from 
those in adults in that 
children may 
demonstrate labored breathing; 
partial 
obstructive hypoventilation (sustained reductions of tidal 
volume due to upper airway flow limitations) with cyclical 
oxygen desaturations; 
hypercapnia; 
and paradoxical breathing. 


Most 
cases of obstructive sleep apnea remain undiagnosed. Therefore, specific attention to 
symptoms of disturbed sleep occurring in association with snoring or breathing pauses and 
physical 
findings that 
increase risk of obstructive sleep apnea hypopnea (e.g., central 
obesity, 
crowded pharyngeal 
airway, elevated blood pressure) is important 
to reduce the chance of failure 
to diagnose this treatable condition. 


Associated Features 


Because of the frequency of nocturnal 
awakenings that 
occur with obstructive sleep apnea 
hypopnea, individuals may report 
symptoms of insomnia. Other common, though nonspecific, 
symptoms of obstructive sleep apnea hypopnea are heartburn, nocturia, morning headaches, dry 
mouth, erectile dysfunction, and reduced libido. Individuals may complain of difficulty breathing 
while lying supine or sleeping. Hypertension may occur in more than 60% of individuals with 
obstructive sleep apnea hypopnea. 


431 


Arterial 
blood gas measurements while the individual 
is awake are usually normal, but 
some 
individuals may demonstrate waking hypoxemia or hypercapnia. This pattern should alert 
the 
clinician to the possibility of coexisting lung disease or hypoventilation. Imaging procedures 
may reveal 
narrowing of the upper airway. Cardiac testing may show evidence of impaired 
ventricular function. Arrhythmias such as sinus pauses, frequent 
atrial 
and ventricular ectopic 
beats, or atrial 
fibrillation may be present 
during sleep. Individuals with severe nocturnal 
oxygen 
desaturation may also have elevated hemoglobin or hematocrit values. 


Prevalence 


Obstructive sleep apnea hypopnea is a very common disorder. Prevalence may be particularly 
high among men as compared with women, ranging from 
2:1 to 4:1; 
older adults; 
and certain 
racial 
and ethnic groups. Prevalence varies cross-nationally, partly because of differences in 
assessment 
methods. Because the disorder is strongly associated with obesity, the rise in obesity 
rates has resulted in an increased prevalence of this disorder. 


In the United States, 13% of men and 6% of women have polysomnographic evidence of 15 
or more obstructive apneas or hypopneas per hour of sleep, and 14% of men and 5% of women 
have more than 5 obstructive apneas or hypopneas per hour of sleep, plus symptoms of daytime 
sleepiness. Gender differences decline in older age, possibly because of increased prevalence in 
females after menopause; 
postmenopausal 
females are 2.6 3.5 times more likely to have 
obstructive sleep apnea compared with premenopausal females. 


In the general 
community, prevalence rates in the United States of undiagnosed obstructive 
sleep apnea hypopnea may be very high in elderly individuals. Obstructive sleep apnea also 
occurs in children, with an estimated prevalence of 1% 4%; 
there is no gender difference among 
prepubertal children. Children who are obese have higher rates. 



Prevalence of obstructive sleep apnea appears to be higher among African Americans than 
among U.S. non-Latinx Whites. An increased prevalence among African Americans, American 
Indians, and Hispanics may be related to higher rates of obesity, which can be associated with 
differential 
exposure to social 
determinants of health, including food insecurity, food deserts, and 
limited access to safe and affordable places for physical activity. 


Development and Course 


The age distribution of obstructive sleep apnea hypopnea has several 
peaks. The first 
occurs in 
children ages 3 8 years when the nasopharynx may be compromised by a relatively large mass 
of tonsillar tissue compared with the size of the upper airway. With growth of the airway and 
regression of lymphoid tissue during later childhood, there is reduction in prevalence. However, 
with the increase of obesity in adolescents, a second peak in prevalence occurs in that 
age group. 
Finally, as obesity prevalence continues to increase in midlife and women enter menopause, rates 
of obstructive sleep apnea hypopnea further increase. The course in older age is unclear; 
prevalence of the disorder may plateau after age 65 years, but 
in some individuals, severity may 
worsen with aging. Polysomnographic results must 
be interpreted in light 
of other clinical 
data. 
Significant 
clinical 
symptoms of insomnia or hypersomnia should be investigated regardless of 
the individual s age. 


Obstructive sleep apnea hypopnea usually has an insidious onset, gradual 
progression, and 
persistent 
course. Typically, the loud snoring has been present 
for many years, often since 
childhood, but 
an increase in its 
severity may lead the individual 
to seek evaluation. Weight 
gain 
may precipitate an increase in symptoms. Although obstructive sleep apnea hypopnea can occur 
at 
any age, it 
most 
commonly manifests among individuals ages 40 60 years. Over 4 5 years, 
the average apnea hypopnea index increases in adults and older individuals by approximately 
two apneas or hypopneas per hour. The apnea hypopnea index is increased and incident 
obstructive sleep apnea hypopnea is greater among 


432 


individuals who are older, who are male, or who have a higher baseline body mass index 
(BMI) or increase their BMI over time. Spontaneous resolution of obstructive sleep apnea 
hypopnea has been reported with weight 
loss, particularly after bariatric surgery. In children, 
seasonal 
variation in obstructive sleep apnea hypopnea has been observed, as has improvement 
with overall growth. 


In young children, the signs and symptoms of obstructive sleep apnea hypopnea may be more 
subtle than in adults, making diagnosis more difficult 
to establish. Polysomnography is useful 
in 
confirming diagnosis. Evidence of fragmentation of sleep on the polysomnogram 
may not 
be as 
apparent 
as in studies of older individuals, possibly because of the high homeostatic drive in 
young individuals. Symptoms such as snoring are usually parent-reported and thus have reduced 
sensitivity. Agitated arousals and unusual 
sleep postures, such as sleeping on the hands and 
knees, may occur. Nocturnal 
enuresis also may occur and should raise the suspicion of 
obstructive sleep apnea hypopnea if it 
recurs in a child who was previously dry at 
night. Children 
may also manifest 
excessive daytime sleepiness, although this is not 
as common or pronounced 
as in adults. Daytime mouth breathing, difficulty in swallowing, and poor speech articulation are 



also common features in children. Children younger than 5 years more often present 
with 
nighttime symptoms, such as observed apneas or labored breathing, than with behavioral 
symptoms (i.e., the nighttime symptoms are more noticeable and more often bring the child to 
clinical 
attention). In children older than 5 years, daytime symptoms such as sleepiness and 
behavioral 
problems (e.g., impulsivity and hyperactivity), attention-deficit/hyperactivity 
disorder, learning difficulties, and morning headaches are more often the focus of concern. 
Children with obstructive sleep apnea hypopnea also may present 
with delayed growth, failure to 
thrive, and developmental 
delays. Although obesity is a less important 
risk factor in young 
children, it nevertheless contributes to the occurrence of obstructive sleep apnea. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
The major risk factors for obstructive sleep apnea hypopnea are obesity 
and male sex. Others include maxillary-mandibular retrognathia or micrognathia, positive family 
history of sleep apnea, genetic syndromes that 
reduce upper airway patency (e.g., Down 
syndrome, Treacher Collins syndrome), adenotonsillar hypertrophy (especially in young 
children), menopause (in females), and various endocrine syndromes (e.g., acromegaly). 
Compared with premenopausal 
females, males are at 
increased risk for obstructive sleep apnea 
hypopnea, possibly reflecting the influences of sex hormones on ventilatory control 
and body fat 
distribution, as well 
as gender differences in airway structure. Medications for mental 
disorders 
and medical 
conditions that 
tend to induce somnolence may worsen the course of apnea 
symptoms if these medications are not managed carefully. 


Obstructive sleep apnea hypopnea has a strong genetic basis, as evidenced by the significant 
familial 
aggregation of the apnea hypopnea index. The prevalence of obstructive sleep apnea 
hypopnea is approximately twice as high among the first-degree relatives of probands with 
obstructive sleep apnea hypopnea as compared with members of control 
families. One-third of 
the variance in the apnea hypopnea index is explained by shared familial 
factors. Although 
genetic markers with diagnostic or prognostic value are not 
yet 
available for use, eliciting a 
family history of obstructive sleep apnea hypopnea should increase the clinical 
suspicion for the 
disorder. 


Culture-Related Diagnostic Issues 


There is a potential 
for sleepiness and fatigue to be reported differently across cultures. In some 
groups, snoring may be considered a sign of normal 
health and thus may not 
trigger concerns, 
leading to underdiagnosis. 


433 


Sex- and Gender-Related Diagnostic Issues 


Menopause, pregnancy, and polycystic ovarian syndrome increase the risk of obstructive sleep 
apnea in females. The transition from 
premenopause to postmenopause is associated with 
increased severity of obstructive sleep apnea. Women may more commonly report 
fatigue, lack 
of energy, or insomnia rather than sleepiness and may underreport snoring. 


Diagnostic Markers 



Polysomnography provides quantitative data on frequency of sleep-related respiratory 
disturbances and associated changes in oxygen saturation and sleep continuity. Validated sleep 
measures (e.g., multiple sleep latency test, maintenance of wakefulness test) may identify 
sleepiness. 


Functional 
Consequences of Obstructive Sleep Apnea Hypopnea 


More than 50% of individuals with moderate to severe obstructive sleep apnea hypopnea report 
symptoms of daytime sleepiness. A twofold increased risk of occupational 
accidents has been 
reported in association with symptoms of snoring and sleepiness. Motor vehicle crashes also 
have been reported to be as much as sevenfold higher among individuals with elevated apnea 
hypopnea index values. Clinicians should be cognizant 
of state government 
requirements for 
reporting this disorder, especially in relationship to commercial 
drivers. Reduced scores on 
measures of health-related quality of life are common in individuals with obstructive sleep apnea 
hypopnea. Although the greatest 
functional 
impact 
is observed in the  vitality  domain, severe 
obstructive sleep apnea negatively affects general 
health and physical 
and social 
functioning as 
well. 


Differential 
Diagnosis 


Primary 
snoring 
and 
other sleep 
disorders. 
Individuals with obstructive sleep apnea hypopnea must 
be differentiated from 
individuals with primary snoring (i.e., otherwise asymptomatic individuals 
who snore and do not 
have abnormalities on overnight 
polysomnography). Individuals with 
obstructive sleep apnea hypopnea may additionally report 
nocturnal 
gasping and choking, which 
can be confused with the presence of asthma or gastroesophageal 
reflux. The presence of 
sleepiness or other daytime symptoms not 
explained by other etiologies suggests the diagnosis of 
obstructive sleep apnea hypopnea, but 
this differentiation requires polysomnography. Definitive 
differential 
diagnosis between hypersomnolence disorder, central 
sleep apnea, sleep-related 
hypoventilation, and obstructive sleep apnea hypopnea also requires polysomnographic studies. 


Obstructive sleep apnea hypopnea must 
be differentiated from 
other causes of sleepiness, 
such as narcolepsy, hypersomnolence disorder, insufficient 
sleep, and circadian rhythm 
sleep 
disorders. Obstructive sleep apnea hypopnea can be differentiated from 
narcolepsy by the 
absence of cataplexy, sleep-related hallucinations, and sleep paralysis and by the presence of 
loud snoring, gasping during sleep, or observed apneas in sleep. Daytime sleep episodes in 
narcolepsy are characteristically shorter, more refreshing, and more often associated with 
dreaming. Obstructive sleep apnea hypopnea shows characteristic apneas and hypopneas and 
oxygen desaturation during nocturnal 
polysomnographic studies. Narcolepsy results in multiple 
sleep-onset 
rapid eye movement 
(REM) periods during the MSLT. Narcolepsy, like obstructive 
sleep apnea hypopnea, may be associated with obesity, and some individuals have concurrent 
narcolepsy and obstructive sleep apnea hypopnea. A diagnosis of narcolepsy does not 
exclude 
the diagnosis of obstructive sleep apnea hypopnea, as the two conditions may co-occur. 


434 


Central 
sleep 
apnea. 
Central 
sleep apnea can be distinguished from 
obstructive sleep apnea by the 
presence of repetitive apneas or hypopneas due to reduction or absence of respiratory effort 
on 



polysomnogram 
recording. Snoring may be present, although it 
may be less prominent 
than 
observed in obstructive sleep apnea hypopnea or absent 
altogether. Individuals with central 
sleep 
apnea often exhibit 
fragmented sleep and may also complain of daytime sleepiness. Central 
sleep 
apnea is seen most 
commonly in individuals with congestive heart 
failure (Cheyne-Stokes 
breathing) or neurological disease, or those using opioid medications. 


Insomnia 
disorder. 
For individuals complaining of difficulty initiating or maintaining sleep or 
early-morning awakenings, insomnia disorder can be differentiated from 
obstructive sleep apnea 
hypopnea by the absence of snoring and the absence of the history, signs, and symptoms 
characteristic of the latter disorder. However, insomnia and obstructive sleep apnea hypopnea 
may coexist, and if so, both disorders may need to be addressed concurrently to improve sleep. 


Panic 
attacks. 
Nocturnal 
panic attacks may include symptoms of gasping or choking during sleep 
that 
may be difficult 
to distinguish clinically from 
obstructive sleep apnea hypopnea. However, 
the lower frequency of episodes, intense autonomic arousal, and lack of excessive sleepiness 
differentiate nocturnal 
panic attacks from 
obstructive sleep apnea hypopnea. Polysomnography 
(or OCST) in individuals with nocturnal 
panic attacks does not 
reveal 
the typical 
pattern of 
apneas or oxygen desaturation characteristic of obstructive sleep apnea hypopnea. Individuals 
with obstructive sleep apnea hypopnea do not provide a history of daytime panic attacks. 


Nocturnal 
asthma. 
Nocturnal 
asthma can often cause sudden awakening from 
sleep with 
symptoms of gasping or choking that 
are indistinguishable from 
dyspneic episodes resulting 
from 
obstructive sleep apnea. However, a history of asthma is generally present 
and 
polysomnography (or OCST) does not 
find evidence of apneas, hypopneas, or oxygen 
desaturation indicative of obstructive apnea. Nevertheless, nocturnal 
asthma and obstructive 
sleep apnea can coexist, and this can make it 
difficult 
to determine the relative contributions of 
each condition. 


Attention-deficit/hyperactivity 
disorder. 
Attention-deficit/hyperactivity disorder in children may 
include symptoms of inattention, academic impairment, hyperactivity, and internalizing 
behaviors, all 
of which may also be symptoms of childhood obstructive sleep apnea hypopnea. 
The presence of other symptoms and signs of childhood obstructive sleep apnea hypopnea (e.g., 
labored breathing or snoring during sleep and adenotonsillar hypertrophy) would suggest 
the 
presence of obstructive sleep apnea hypopnea. Obstructive sleep apnea hypopnea and attentiondeficit/
hyperactivity disorder may commonly co-occur, and there may be causal 
links between 
them; 
therefore, risk factors such as enlarged tonsils, obesity, or a family history of sleep apnea 
may help alert the clinician to their co-occurrence. 


Substance/medication-induced 
insomnia 
or hypersomnia. 


Substance use and substance withdrawal 
(including medications) can produce insomnia or hypersomnia. A careful 
history is usually 
sufficient to identify the relevant substance/medication, and follow-up shows improvement of the 
sleep disturbance after discontinuation of the substance/medication. In other cases, the use of a 
substance/medication (e.g., alcohol, barbiturates, benzodiazepines, opiates) has been shown to 
exacerbate obstructive sleep apnea hypopnea. An individual 
with symptoms and signs consistent 
with obstructive sleep apnea hypopnea should receive that 
diagnosis, even in the presence of 
concurrent substance use that is exacerbating the condition. 


Comorbidity 



Systemic hypertension, coronary artery disease, heart 
failure, stroke, diabetes, and increased 
mortality are consistently associated with obstructive sleep apnea hypopnea. Risk 


435 


estimates vary from 
30% to as much as 300% for moderate to severe obstructive sleep apnea 
hypopnea. Obstructive sleep apnea and cardiovascular disease are strongly related, and treatment 
of obstructive sleep apnea reduces morbidity and mortality of cardiovascular disease. Ethnic and 
racialized groups that have not received adequate health care may be at higher risk for undetected 
cardiovascular risk factors associated with obstructive sleep apnea. Evidence of pulmonary 
hypertension and right 
heart 
failure (e.g., cor pulmonale, ankle edema, hepatic congestion) is rare 
in obstructive sleep apnea hypopnea and when present 
indicates either very severe disease or 
associated hypoventilation or cardiopulmonary comorbidities. Obstructive sleep apnea hypopnea 
also may occur with increased frequency in association with a number of medical 
or neurological 
conditions (e.g., cerebrovascular disease, Parkinson s disease). Physical 
findings reflect 
the co-
occurrence of these conditions. 


As many as one-third of individuals referred for evaluation of obstructive sleep apnea 
hypopnea report 
symptoms of depression, with as many of 10% having depression scores 
consistent 
with moderate to severe depression. Severity of obstructive sleep apnea hypopnea, as 
measured by the apnea hypopnea index, has been found to be correlated with severity of 
symptoms of depression. This association may be stronger in men than in women. 


Relationship to International 
Classification of Sleep Disorders 


The International 
Classification of 
Sleep Disorders, 
3rd Edition (ICSD-3), differentiates 11 
subtypes of  sleep-related breathing disorders,  including central 
sleep apneas (CSAs) (e.g., 
primary CSA, CSA due to a medical/neurological 
condition, CSA due to a substance or 
medication), obstructive sleep apnea (adult 
and pediatric), and sleep-related hypoventilation 
disorders. 


Central 
Sleep 
Apnea 


Diagnostic Criteria 


A. 
Evidence 
by polysomnography of 
five 
or more 
central apneas per hour of 
sleep. 
B. 
The 
disorder is not 
better explained 
by another current 
sleep 
disorder. 
Specify 
whether: 
G47.31 
Idiopathic 
central 
sleep 
apnea: 
Characterized 
by repeated 
episodes of 
apneas and 
hypopneas during 
sleep 
caused 
by variability in 
respiratory effort 
but 
without 
evidence 
of 
airway obstruction. 
R06.3 
Cheyne-Stokes 
breathing: 
A 
pattern 
of 
periodic crescendo-decrescendo 


variation 
in 
tidal volume 
that 
results in 
central apneas and 
hypopneas at 
a 
frequency of 
at 
least 
five 
events per hour, 
accompanied 
by frequent 
arousal. 



G47.37 
Central 
sleep 
apnea 
comorbid 
with 
opioid 
use: 
The 
pathogenesis of 
this subtype 
is attributed 
to 
the 
effects of 
opioids on 
the 
respiratory rhythm 
generators in 
the 
medulla 
as well as the 
differential effects on 
hypoxic versus 
hypercapnic respiratory drive. 


Coding 
note 
(for G47.37 
code 
only): 
When 
an 
opioid 
use 
disorder is present, 
first 
code 
the 
opioid 
use 
disorder: 
F11.10 
mild 
opioid 
use 
disorder or F11.20 
moderate 
or severe 
opioid 
use 
disorder; 
then 
code 
G47.37 
central sleep 
apnea 
comorbid 
with 
opioid 
use. 
When 
an 
opioid 
use 
disorder is not 
present 
(e.g., 
after a 
one-time 
heavy 
use 
of 
the 
substance), 
code 
only G47.37 
central sleep 
apnea 
comorbid 
with 
opioid 
use. 


436 


Specify 
current 
severity: 
Severity of 
central sleep 
apnea 
is graded 
according 
to 
the 
frequency of 
the 
breathing 
disturbances as well as the 
extent 
of 
associated 
oxygen 
desaturation 
and 
sleep 
fragmentation 
that 
occur as a 
consequence 
of 
repetitive 
respiratory 
disturbances. 


Subtypes 


There are several 
subtypes of central 
sleep apnea. Idiopathic central 
sleep apnea (alternatively 
termed primary central 
sleep apnea) and central 
sleep apnea with Cheyne-Stokes breathing are 
characterized by increased gain of the ventilatory control 
system, also referred to as high loop 
gain, 
which leads to instability in ventilation and PaCO2 
levels. This instability is termed 


periodic breathing 
and can be recognized by hyperventilation alternating with hypoventilation. 
Individuals with these disorders typically have pCO2 
levels while awake that 
are slightly 
hypocapnic or normocapnic. Central 
sleep apnea may also manifest 
during initiation of treatment 
of obstructive sleep apnea hypopnea (termed treatment-emergent 
central 
sleep apnea) or may 
occur in association with obstructive sleep apnea hypopnea syndrome. The occurrence of central 
sleep apnea in association with obstructive sleep apnea is also considered to be due to high loop 
gain. In contrast, the pathogenesis of central 
sleep apnea comorbid with opioid use has been 
attributed to the effects of opioids on the respiratory rhythm 
generators in the medulla as well 
as 
to its differential 
effects on hypoxic versus hypercapnic respiratory drive. These individuals may 
have elevated pCO2 
levels while awake. Individuals receiving chronic methadone maintenance 


therapy have been noted to have increased somnolence and depression, although the role of 
opioid-induced breathing disorders in causing these problems has not 
been studied. Similarly, 
central 
apnea due to a medical 
disorder without 
Cheyne-Stokes breathing is a result 
of a 
pathological process that affects brain-stem ventilatory control centers. 


Specifiers 


An increase in the central 
apnea index (i.e., number of central 
apneas per hour of sleep) reflects 
an increase in severity of central 
sleep apnea. Sleep continuity and quality may be markedly 
impaired with reductions in restorative stages of non rapid eye movement 
(NREM) sleep (i.e., 



decreased slow-wave sleep [stage N3]). In individuals with severe Cheyne-Stokes breathing, the 
pattern can also be observed during resting wakefulness, a finding that 
is thought 
to be a 
prognostic marker for increased mortality. 


Diagnostic Features 


Central 
sleep apnea disorders are characterized by repeated episodes of apneas and hypopneas 
during sleep caused by variability in respiratory effort. These are disorders of ventilatory control 
in which respiratory events occur in a periodic or intermittent 
pattern. Idiopathic central 
sleep 
apnea 
is characterized by sleepiness, insomnia, and awakenings due to dyspnea in association 
with five or more central 
apneas per hour of sleep. Individuals with heart 
failure, stroke, or renal 
failure who have central 
sleep apnea typically have a breathing pattern called Cheyne-Stokes 
breathing, 
which is characterized by a pattern of periodic crescendo-decrescendo variation in 
tidal 
volume that 
results in central 
apneas and hypopneas occurring at 
a frequency of at 
least 
five 
events per hour. Events are often associated with arousal, but 
arousals are not 
required for the 
diagnosis. Central 
sleep apnea observed at 
high altitude occurs after ascent 
to high altitude, 
generally at least 2,500 meters above sea level. Central and obstructive sleep apneas may coexist; 
a diagnosis of central 
sleep apnea hypopnea requires that 
central 
events be > 50% of the total 
number of respiratory events. 


Alterations in neuromuscular control 
of breathing can occur in association with medications 
or substances, which can cause or exacerbate impairments of respiratory rhythm 
and ventilation. 
Individuals taking medications with these effects may have a sleep-related breathing disorder 
that could contribute to sleep disturbances and symptoms such 


437 


as sleepiness, confusion, and depression. Specifically, chronic use of 
long-acting opioid 
medications 
is often associated with impairment 
of respiratory control 
leading to central 
sleep 
apnea. 


Associated Features 


Individuals with central 
sleep apnea hypopneas may present 
with sleepiness or insomnia. They 
may have complaints of sleep fragmentation, including awakening with dyspnea. Some 
individuals are asymptomatic. Obstructive sleep apnea hypopnea can coexist 
with Cheyne-
Stokes breathing, and thus snoring and abruptly terminated obstructive events may be observed 
during sleep. 


Physical 
findings seen in individuals with a Cheyne-Stokes breathing pattern relate to its risk 
factors. Findings consistent 
with heart 
failure, such as jugular venous distension, S3 heart 
sound, 
lung crackles, and lower-extremity edema, may be present. 


Prevalence 


The prevalence of idiopathic central 
sleep apnea is unknown but 
thought 
to be rare. The 
prevalence of Cheyne-Stokes breathing is high in individuals with depressed cardiac ventricular 
ejection fraction. In individuals with an ejection fraction of < 45%, the prevalence has been 
reported to range from 
15% to 44%. The gender ratio for prevalence in North America, Europe, 



and Australia is even more highly skewed toward men than for obstructive sleep apnea 
hypopnea. Prevalence increases with age, and most 
individuals with the disorder are older than 
60 years. Cheyne-Stokes breathing occurs in approximately 20% of individuals with acute stroke 
as assessed in Barcelona and Toronto. Central 
sleep apnea comorbid with opioid use occurs in 
approximately 24% of individuals taking opioids chronically for nonmalignant 
pain and similarly 
in individuals receiving methadone maintenance therapy as seen in several 
high-income 
countries. Higher opioid doses are associated with greater severity, especially at 
morphine-
equivalent 
daily dosages > 200 mg. In children assessed in France and Canada, the prevalence 
ranges from 4% to 6%. 


Development and Course 


Polysomnography parameters for diagnosing central 
sleep apnea are different 
for children than 
for adults and comprise any of the following: 
1) cessation of airflow and respiratory effort 
for 
more than 20 seconds, two breath cycles that 
are associated with an arousal 
from 
sleep, or > 3% 
oxygen desaturation; or 2) two breath cycles that are associated with bradycardia. 


The onset 
of Cheyne-Stokes breathing appears tied to the development 
of heart 
failure. The 
Cheyne-Stokes breathing pattern is associated with oscillations in heart 
rate, blood pressure, and 
oxygen desaturation, and elevated sympathetic nervous system 
activity that 
can promote 
progression of heart 
failure. The clinical 
significance of Cheyne-Stokes breathing in the setting 
of stroke is not 
known, but 
Cheyne-Stokes breathing may be a transient 
finding that 
resolves 
with time after acute stroke. Central 
sleep apnea comorbid with opioid use has been documented 
with chronic use (i.e., several months). 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Cheyne-Stokes breathing is frequently present 
in individuals with heart 
failure. The coexistence of atrial 
fibrillation further increases risk, as do older age and male sex. 
Cheyne-Stokes breathing is also seen in association with acute stroke and possibly renal 
failure. 
The underlying ventilatory instability in the setting of heart 
failure has been attributed to 
increased ventilatory chemosensitivity and hyperventilation due to pulmonary vascular 
congestion and circulatory delay. Central 
sleep apnea is seen in individuals taking long-acting 
opioids. In children, central sleep apnea can be found in 


438 


individuals with congenital 
abnormalities, particularly Arnold-Chiari 
malformation, or comorbid 
medical 
conditions such as gastroesophageal 
reflux. Rarely, central 
sleep apnea resulting from 
a 
congenital 
condition may not 
manifest 
until 
adulthood (e.g., Arnold-Chiari 
malformation and 
congenital central hypoventilation). 


Diagnostic Markers 


Polysomnography is used to characterize the breathing characteristics of each breathing-related 
sleep disorder subtype. Central 
sleep apneas are recorded when periods of breathing cessation for 
longer than 10 seconds occur. Cheyne-Stokes breathing is characterized by a pattern of periodic 
crescendo-decrescendo variation in tidal 
volume that 
results in central 
apneas and hypopneas 



occurring at 
a frequency of at 
least 
five events per hour with the number of central 
apneas and 
hypopneas > 50% of the total 
number of apneas and hypopneas. The cycle length of Cheyne-
Stokes breathing (or time from 
end of one central 
apnea to the end of the next 
apnea) is about 
60 
seconds. 


Functional 
Consequences of Central 
Sleep Apnea 


Idiopathic central 
sleep apnea has been reported to cause symptoms of disrupted sleep, including 
insomnia and sleepiness. Cheyne-Stokes breathing with comorbid heart 
failure has been 
associated with excessive sleepiness, fatigue, and insomnia, although many individuals may be 
asymptomatic. Coexistence of heart 
failure and Cheyne-Stokes breathing may be associated with 
increased cardiac arrhythmias and increased mortality or cardiac transplantation. Individuals with 
central 
sleep apnea comorbid with opioid use may present 
with symptoms of sleepiness or 
insomnia. 


Differential 
Diagnosis 


Idiopathic central 
sleep apnea must 
be distinguished from 
other breathing-related sleep disorders, 
other sleep disorders, and medical 
conditions and mental 
disorders that 
cause sleep 
fragmentation, sleepiness, and fatigue. This is achieved using polysomnography. 
Other breathing-related 
sleep 
disorders 
and 
sleep 
disorders. 
Central 
sleep apnea can be distinguished 


from 
obstructive sleep apnea hypopnea by the presence of at 
least 
five central 
apneas per hour of 
sleep. These conditions may co-occur, but 
central 
sleep apnea is considered to predominate when 
central respiratory events are > 50% of the total number of respiratory events. 


Cheyne-Stokes breathing can be distinguished from 
other mental 
disorders, including other 
sleep disorders, and other medical 
conditions that 
cause sleep fragmentation, sleepiness, and 
fatigue based on the presence of a predisposing condition (e.g., heart 
failure or stroke) and signs 
and polysomnographic evidence of the characteristic breathing pattern. Polysomnographic 
respiratory findings can help distinguish Cheyne-Stokes breathing from 
insomnia due to other 
medical 
conditions. For example, central 
sleep apnea due to high-altitude periodic breathing has 
a pattern that 
resembles Cheyne-Stokes breathing but 
has a shorter cycle time, occurs only at 
high altitude, and is not associated with heart failure. 


Central 
sleep apnea comorbid with opioid use can be differentiated from 
other types of 
breathing-related sleep disorders based on the use of long-acting opioid medications in 
conjunction with polysomnographic evidence of central 
apneas and periodic or ataxic breathing. 
It 
can be distinguished from 
insomnia due to drug or substance use based on polysomnographic 
evidence of central sleep apnea. 


Comorbidity 


Central 
sleep apnea disorders are frequently present 
in users of long-acting opioids, such as 
methadone. Individuals taking these medications have a breathing-related sleep disorder that 
could contribute to sleep disturbances and symptoms such as sleepiness, 


439 


confusion, and depression. While the individual 
is asleep, breathing patterns such as central 



apneas, periodic apneas, and ataxic breathing may be observed. Obstructive sleep apnea 
hypopnea may coexist 
with central 
sleep apnea, and features consistent 
with this condition can 
also be present 
(see  Obstructive Sleep Apnea Hypopnea  earlier in this chapter). Cheyne-Stokes 
breathing is more commonly observed in association with conditions that 
include heart 
failure, 
stroke, and renal 
failure and is seen more frequently in individuals with atrial 
fibrillation. 
Individuals with Cheyne-Stokes breathing are more likely to be older, to be male, and to have 
lower weight than individuals with obstructive sleep apnea hypopnea. 


Relationship to International 
Classification of Sleep Disorders 


The International 
Classification of 
Sleep Disorders, 3rd Edition (ICSD-3), includes eight 
subtypes of central 
sleep apnea (central 
sleep apnea with Cheyne-Stokes breathing, central 
apnea 
due to a medical 
disorder without 
Cheyne-Stokes breathing, central 
sleep apnea due to high-
altitude periodic breathing, central 
sleep apnea due to a medication or substance, primary central 
sleep apnea, primary central 
sleep apnea of infancy, primary central 
sleep apnea of prematurity, 
and treatment-emergent 
central 
sleep apnea). As in DSM-5, most 
of these diagnoses require a 
frequency of 5 or more central 
events per hour of sleep. In addition, ICSD-3 criteria also require 
the presence of signs or symptoms (e.g., complaints of insomnia or daytime sleepiness). Central 
events must 
constitute at 
least 
50% of the total 
number of apneas and hypopneas. Primary central 
sleep apnea of infancy and primary central 
sleep apnea of prematurity have their own distinct 
criteria sets that differ from adult forms of central sleep apnea. 


Sleep-Related 
Hypoventilation 


Diagnostic Criteria 


A. 
Polysomnograpy demonstrates episodes of 
decreased 
respiration 
associated 
with 
elevated 
CO2 
levels. 
(Note: 
In 
the 
absence 
of 
objective 
measurement 
of 
CO2, 
persistent 
low levels of 
hemoglobin 
oxygen 
saturation 
unassociated 
with 
apneic/hypopneic events may indicate 
hypoventilation.) 


B. 
The 
disturbance 
is not 
better explained 
by another current 
sleep 
disorder. 
Specify 
whether: 
G47.34 
Idiopathic 
hypoventilation: 
This subtype 
is not 
attributable 
to 
any 
readily identified 
condition. 
G47.35 
Congenital 
central 
alveolar hypoventilation: 
This subtype 
is a 
rare 


congenital disorder in 
which 
the 
individual typically presents in 
the 
perinatal 


period 
with 
shallow breathing, 
or cyanosis and 
apnea 
during 
sleep. 
G47.36 
Comorbid 
sleep-related 
hypoventilation: 
This subtype 
occurs as a 
consequence 
of 
a 
medical condition, 
such 
as a 
pulmonary disorder (e.g., 
interstitial lung 
disease, 
chronic obstructive 
pulmonary disease) or a 
neuromuscular or chest 
wall disorder (e.g., 
muscular dystrophies, 
postpolio 
syndrome, 
cervical spinal cord 
injury, 
kyphoscoliosis), 
or medications (e.g., 



benzodiazepines, 
opiates). 
It 
also 
occurs with 
obesity (obesity hypoventilation 
disorder), 
where 
it 
reflects a 
combination 
of 
increased 
work of 
breathing 
due 
to 
reduced 
chest 
wall compliance 
and 
ventilation-perfusion 
mismatch 
and 
variably 
reduced 
ventilatory drive. 
Such 
individuals usually are 
characterized 
by body 
mass index of 
greater than 
30 
and 
hypercapnia 
during 
wakefulness (with 
a 
pCO2 


of 
greater than 
45), 
without 
other evidence 
of 
hypoventilation. 


440 


Specify 
current 
severity: 
Severity is graded 
according 
to 
the 
degree 
of 
hypoxemia 
and 
hypercarbia 
present 
during 
sleep 
and 
evidence 
of 
end 
organ 
impairment 
due 
to 
these 
abnormalities (e.g., 
right-sided 
heart 
failure). 
The 
presence 
of 
blood 
gas 
abnormalities during 
wakefulness is an 
indicator of 
greater severity. 


Subtypes 


Subtypes of sleep-related hypoventilation include the following: 



Idiopathic hypoventilation, also referred to as idiopathic central 
alveolar hypoventilation, is characterized by reduction of 
tidal 
volume and elevated CO2 
during sleep, in the absence of 
any identifiable comorbidity that 
would account 
for 
the 
hypoventilation. 
Congenital 
central 
alveolar hypoventilation 
is a rare disorder 
associated with mutation of 
the gene PHOX2B. It 
typically 
manifests at birth. 
Comorbid sleep-related hypoventilation 
is due to one of 
numerous potential 
comorbidities, including pulmonary disease 
(e.g., chronic obstructive pulmonary disease [COPD]), chest 
wall 
abnormalities (e.g., kyphoscoliosis), neuromuscular 
disease (e.g., amyotrophic lateral 
sclerosis), and obesity (referred to as obesity hypoventilation), as well 
as use of 
medications or substances, especially opioids. 
Diagnostic Features 


Sleep-related hypoventilation can occur independently or, more frequently, comorbid with 
medical 
or neurological 
disorders, medication use, or substance use disorder. Although 
symptoms are not 
mandatory to make this diagnosis, individuals often report 
excessive daytime 
sleepiness, frequent 
arousals and awakenings during sleep, morning headaches, and insomnia 
complaints. 


Associated Features 


Individuals with sleep-related hypoventilation can present 
with sleep-related complaints of 
insomnia or sleepiness. Episodes of orthopnea can occur in individuals with diaphragm 
weakness. Headaches upon awakening may be present. During sleep, episodes of shallow 
breathing may be observed, and obstructive sleep apnea hypopnea or central 
sleep apnea may 
coexist. Consequences of ventilatory insufficiency, including pulmonary hypertension, cor 
pulmonale (right 
heart 
failure), polycythemia, and neurocognitive dysfunction, can be present. 



With progression of ventilatory insufficiency, blood gas abnormalities extend into wakefulness. 
Features of a medical 
condition causing sleep-related hypoventilation can also be present. 
Episodes of hypoventilation may be associated with frequent 
arousals or bradytachycardia. 
Individuals may complain of excessive sleepiness and insomnia or morning headaches or may 
present 
with findings of neurocognitive dysfunction or depression. Hypoventilation may not 
be 
present during wakefulness. 


Prevalence 


Idiopathic sleep-related hypoventilation in adults is very uncommon. The prevalence of 
congenital 
central 
alveolar hypoventilation is unknown, but 
the disorder is rare. Comorbid sleep-
related hypoventilation (i.e., hypoventilation comorbid with other conditions, such as COPD, 
neuromuscular disorders, or obesity) is more common. 


The prevalence of comorbid sleep-related hypoventilation due to obesity in the general 
population is estimated to be approximately 0.14% 0.6% based on national 
obesity rates and 
prevalence of obstructive sleep apnea across several 
countries. Increasing rates of obesity are 
associated with increasing prevalence of comorbid sleep-related hypoventilation 


441 


due to obesity. In individuals referred to a sleep clinic who have a body mass index > 35 
kg/m2, prevalence may be as high as 42%. 


Development and Course 


Idiopathic sleep-related hypoventilation is thought 
to be a slowly progressive disorder of 
respiratory impairment. When sleep-related hypoventilation disorder occurs comorbidly with 
other disorders (e.g., COPD, neuromuscular disorders, obesity), disease severity reflects the 
severity of the underlying condition, and the disorder progresses as the condition worsens. 
Complications such as pulmonary hypertension, cor pulmonale, cardiac dysrhythmias, 
polycythemia, neurocognitive dysfunction, and worsening respiratory failure can develop with 
increasing severity of blood gas abnormalities. 


Congenital 
central 
alveolar hypoventilation usually manifests at 
birth with shallow, erratic, or 
absent 
breathing. This disorder can also manifest 
during infancy, childhood, and adulthood 
because of variable penetrance of the PHOX2B mutation. 


Risk and Prognostic Factors 


Environmental. 
Ventilatory drive can be reduced in individuals who are using central 
nervous 


system depressants, including benzodiazepines, opiates, and alcohol. 
Genetic 
and 
physiological. 
Idiopathic sleep-related hypoventilation is associated with reduced 
ventilatory drive due to a blunted chemoresponsiveness to CO2 
(reduced respiratory drive; 
i.e., 


 won t 
breathe ), reflecting underlying neurological 
deficits in centers governing the control 
of 
ventilation. More commonly, sleep-related hypoventilation is comorbid with another medical 
condition, such as a pulmonary disorder, a neuromuscular or chest 
wall 
disorder, or 
hypothyroidism, or with use of medications (e.g., benzodiazepines, opiates). In these conditions, 



the hypoventilation may be a consequence of increased work of breathing and/or impairment 
of 
respiratory muscle function (i.e.,  can t breathe ) or reduced respiratory drive. 


Neuromuscular disorders influence breathing through impairment 
of respiratory motor 
innervation or respiratory muscle function. They include conditions such as amyotrophic lateral 
sclerosis, spinal 
cord injury, diaphragmatic paralysis, myasthenia gravis, Lambert-Eaton 
syndrome, toxic or metabolic myopathies, postpolio syndrome, and Charcot-Marie-Tooth 
syndrome. 


Congenital 
central 
alveolar hypoventilation is a genetic disorder attributable to mutations of 
PHOX2B, 
a gene that 
is crucial 
for the development 
of the embryonic autonomic nervous system 
and neural 
crest 
derivatives. Children with congenital 
central 
alveolar hypoventilation show 
blunted ventilatory responses to hypercapnia, especially in non rapid eye movement sleep. 


Sex- and Gender-Related Diagnostic Issues 


Gender distributions for sleep-related hypoventilation occurring in association with comorbid 
conditions reflect 
the gender distributions of the comorbid conditions. For example, COPD is 
more frequently present 
in men and with increasing age. Contrary to previous data, obesity 
hypoventilation is now thought 
to occur equally between genders, and in some studies there may 
be even a slightly greater prevalence in women. 


Diagnostic Markers 


Sleep-related hypoventilation is diagnosed using polysomnography, which demonstrates sleep-
related hypoxemia and hypercapnia that is not better explained by another breathing-related sleep 
disorder. The documentation of 1) increased arterial 
pCO2 
levels to > 55 mmHg during sleep or 


2) a = 10-mmHg increase in pCO2 levels (to a level that also exceeds 
442 


50 mmHg) during sleep in comparison to awake supine values, in each case exceeding 10 
minutes  duration, is the gold standard for diagnosis. However, obtaining arterial 
blood gas 
determinations during sleep is impractical, and non-invasive measures of pCO2 
have not 
been 


adequately validated during sleep and are not 
widely used during polysomnography in adults. 
Prolonged and sustained decreases in oxygen saturation (oxygen saturation of < 90% for more 
than 5 minutes with a nadir of at 
least 
85%, or oxygen saturation of < 90% for at 
least 
30% of 
sleep time) in the absence of evidence of upper airway obstruction are often used as an indication 
of sleep-related hypoventilation; 
however, this finding is not 
specific, as there are other potential 
causes of hypoxemia, such as that due to lung disease. 


Children with congenital 
central 
alveolar hypoventilation are more likely to have disorders of 
the autonomic nervous system, Hirschsprung s disease, neural 
crest 
tumors, and characteristic 
box-shaped face (i.e., the face is short relative to its width). 


Functional 
Consequences of Sleep-Related Hypoventilation 


The consequences of sleep-related hypoventilation are related to the effects of chronic exposure 
to hypercapnia and hypoxemia. These blood gas derangements cause vasoconstriction of the 



pul 
si 
brai 
cardi 
respi 


Di 


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hypovent 
skel 
or 
ot 


O 


obst 
on 
oxygen 
and 
pat 
hypovent 
associ 
have com 


Comorbi 


S 
int 
dyst 
m 
cent 
occur 
usual 
hypoxem 


hypopnea 
T 
hypovent 
represent 


Rel 


T 
subt 
syndrom 
IC 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
477 



Sexual 
Dysfunctions 


Sexual dysfunctions 
include delayed ejaculation, erectile disorder, female orgasmic 
disorder, female sexual 
interest/arousal 
disorder, genito-pelvic pain/penetration disorder, male 
hypoactive sexual 
desire disorder, premature (early) ejaculation, substance/medication-induced 
sexual 
dysfunction, other specified sexual 
dysfunction, and unspecified sexual 
dysfunction. 
Sexual 
dysfunctions are a heterogeneous group of disorders that 
are typically characterized by a 
clinically significant 
disturbance in a person s ability to respond sexually or to experience sexual 
pleasure. An individual 
may have several 
sexual 
dysfunctions at 
the same time. In such cases, all 
of the dysfunctions should be diagnosed. 


Clinical 
judgment 
should be used to determine if the sexual 
difficulties are the result 
of 
inadequate sexual 
stimulation; 
in these cases, there may still 
be a need for care, but 
a diagnosis 
of a sexual 
dysfunction would not 
be made. These cases may include, but 
are not 
limited to, 
conditions in which lack of knowledge about 
effective stimulation prevents the experience of 
arousal or orgasm. 


Subtypes are used to designate the onset 
of the difficulty. In many individuals with sexual 
dysfunctions, the time of onset 
may indicate different 
etiologies and interventions. Lifelong 
refers to a sexual 
problem 
that 
has been present 
from 
first 
sexual 
experiences, and acquired 
applies to sexual 
dysfunctions that 
develop after a period of relatively normal 
sexual 
function. 
Generalized 
refers to sexual 
difficulties that 
are not 
limited to certain types of stimulation, 
situations, or partners, and situational 
refers to sexual 
difficulties that 
only occur with certain 
types of stimulation, situations, or partners. 


In addition to the lifelong/acquired and generalized/situational 
subtypes, a number of factors 
must 
be considered during the assessment 
of sexual 
dysfunction, given that 
they may be relevant 
to etiology or treatment 
and may contribute, to varying degrees, across individuals: 
1) partner 
factors (e.g., partner s sexual 
problems; 
partner s health status); 
2) relationship factors (e.g., poor 
communication; 
discrepancies in desire for sexual 
activity); 
3) individual 
vulnerability factors 
(e.g., poor body image; 
history of sexual 
or emotional 
abuse), psychiatric comorbidity (e.g., 
depression, anxiety), or stressors (e.g., job loss, bereavement); 
4) cultural 
or religious factors 
(e.g., inhibitions related to prohibitions against 
sexual 
activity or pleasure; 
attitudes toward 
sexuality); and 5) medical factors relevant to prognosis, course, or treatment. 


Clinical 
judgment 
about 
the diagnosis of sexual 
dysfunction should take into consideration 
cultural 
factors that 
may influence expectations or engender prohibitions about 
the experience of 
sexual 
pleasure. Aging and relationship duration may be associated with a normative decrease in 
sexual response. 


Sexual 
response has a requisite biological 
underpinning, yet 
is usually experienced in an 
intrapersonal, interpersonal, and cultural 
context. Thus, sexual 
function involves a complex 
interaction among biological, sociocultural, and psychological 
factors. In many clinical 
contexts, 
a precise understanding of the etiology of a sexual 
problem 
is unknown. Nonetheless, a sexual 



dysfunction diagnosis requires ruling out 
problems that 
are better explained by a nonsexual 
mental disorder, by the effects of a substance (e.g., drug or 


478 


medication), by a medical 
condition (e.g., due to pelvic nerve damage), or by severe 
relationship distress, partner violence, or other stressors. 


The population of gender-diverse persons, including transgender, nonbinary, and agender, 
may not 
identify with or appear to fit 
into the existing sex-and gender-based diagnostic 
categories described in this chapter. Despite the names given to male hypoactive sexual 
desire 
disorder and female sexual 
interest 
arousal 
disorder, the diagnostic criteria describe symptoms 
and experiences that 
are not 
dependent 
on the individual s specific sex or gender. As such, either 
diagnosis can be applied to gender-diverse individuals based on clinical 
judgment. For diagnoses 
linked to reproductive anatomy (e.g., erectile dysfunction, premature [early] ejaculation, delayed 
ejaculation, and genito-pelvic pain/penetration disorder), diagnoses should be based on the 
individual s current 
anatomy and not 
on the individual s sex assigned at 
birth. Much more 
research is needed to understand experiences of sexual 
dysfunction among gender-diverse 
persons. In the meantime, as with all 
categories in DSM, clinicians should use their best 
judgment. 


If the sexual 
dysfunction is mostly explainable by another nonsexual 
mental 
disorder (e.g., 
depressive or bipolar disorder, anxiety disorder, posttraumatic stress disorder, psychotic 
disorder), then only the other mental 
disorder diagnosis should be made. If the problem 
is 
thought 
to be better explained by the use/misuse or discontinuation of a drug or substance, it 
should be diagnosed accordingly as a substance/medication-induced sexual 
dysfunction. If the 
sexual 
dysfunction is attributable to another medical 
condition (e.g., peripheral 
neuropathy), the 
person would not 
receive a psychiatric diagnosis. If severe relationship distress, partner violence, 
or significant 
stressors better explain the sexual 
difficulties, then a sexual 
dysfunction diagnosis 
is not 
made, but 
an appropriate Z 
code for the relationship problem 
or stressor may be listed 
(e.g., Z63.0 Relationship distress with spouse or intimate partner); 
see the chapter  Other 
Conditions That 
May Be a Focus of Clinical 
Attention.  In many cases, a precise etiological 
relationship between another condition (e.g., a medical 
condition) and a sexual 
dysfunction 
cannot 
be established. It 
is possible to have a diagnosis of a sexual 
dysfunction and a coexisting 
medical 
condition, nonsexual 
mental 
disorder, or use/misuse or discontinuation of a drug or 
substance; and it is possible to have one or more diagnoses of sexual dysfunction. 


Delayed 
Ejaculation 


Diagnostic Criteria 
F52.32 


A. 
Either of 
the 
following 
symptoms must 
be 
experienced 
on 
almost 
all or all 
occasions (approximately 75% 100%) of 
partnered 
sexual activity (in 
identified 
situational contexts or, 
if 
generalized, 
in 
all contexts), 
and 
without 
the 
individual 
desiring 
delay: 

1. 
Marked 
delay in 
ejaculation. 
2. 
Marked 
infrequency or absence 
of 
ejaculation. 
B. 
The 
symptoms in 
Criterion 
A 
have 
persisted 
for a 
minimum duration 
of 
approximately 6 
months. 
C. 
The 
symptoms in 
Criterion 
A 
cause 
clinically significant 
distress in 
the 
individual. 
D. 
The 
sexual dysfunction 
is not 
better explained 
by a 
nonsexual mental disorder or 
as a 
consequence 
of 
severe 
relationship 
distress or other significant 
stressors 
and 
is not 
attributable 
to 
the 
effects of 
a 
substance/medication 
or another 
medical condition. 
Specify 
whether: 


Lifelong: 
The 
disturbance 
has been 
present 
since 
the 
individual became 
sexually active. 
Acquired: 
The 
disturbance 
began 
after a 
period 
of 
relatively normal sexual 


function. 


479 


Specify 
whether: 
Generalized: 
Not 
limited 
to 
certain 
types of 
stimulation, 
situations, 
or partners. 
Situational: 
Only occurs with 
certain 
types of 
stimulation, 
situations, 
or partners. 


Specify 
current 
severity: 
Mild: 
Evidence 
of 
mild 
distress over the 
symptoms in 
Criterion 
A. 
Moderate: 
Evidence 
of 
moderate 
distress over the 
symptoms in 
Criterion 
A. 
Severe: 
Evidence 
of 
severe 
or extreme 
distress over the 
symptoms in 
Criterion 


A. 


Diagnostic Features 


The essential 
feature of delayed ejaculation is a marked delay in or inability to achieve 
ejaculation or marked infrequency of ejaculation on all 
or almost 
all 
occasions of partnered 
sexual 
activity, despite the presence of adequate sexual 
stimulation and the desire to ejaculate 
(Criterion A). In order to qualify for a DSM-5 diagnosis of delayed ejaculation, the symptoms 
must 
have persisted for a minimum 
duration of approximately 6 months (Criterion B) and must 
cause clinically significant 
distress in the individual 
(Criterion C). The partnered sexual 
activity 
may include manual, oral, coital, or anal 
stimulation. In most 
cases, the diagnosis will 
be made 
by self-report, although for men in heterosexual 
partnered relationships, it 
is frequently the 
female partner s distress that 
motivates treatment 
seeking. It 
is common for men who present 
with delayed ejaculation to be able to ejaculate with self-stimulation, but 
not 
during partnered 
sexual activity. 


The definition of  delay  does not 
have precise boundaries, as there is no consensus as to 
what 
constitutes a reasonable time to reach orgasm 
or what 
is unacceptably long for most 
men 
and their sexual 
partners. Although the definitions of delayed ejaculation apply equally well 
to 



both heterosexual 
and homosexual 
orientation, the vast 
majority of the research focus has been 
based on the concept 
of intravaginal 
latency, and therefore male-female intercourse. The findings 
from 
those studies document 
that 
the majority of men s intravaginal 
ejaculatory latency time 
(IELT) range is approximately 4 10 minutes. There is also no clear diagnostic delineation 
between delayed ejaculation as a sexual 
dysfunction and delay that 
is a consequence of normal 
aging. Therefore, the diagnosis of delayed ejaculation is based on clinical 
judgment, taking into 
consideration the individual s psychosexual 
and medical 
history, age, relationship context, and 
sexual 
stimulation patterns and behaviors. The diagnosis of delayed ejaculation should not 
be 
given if the clinician judges that 
the individual s dissatisfaction is entirely attributable to 
unrealistic expectations. 


Associated Features 


The man and his partner may report 
prolonged thrusting to achieve orgasm 
to the point 
of 
exhaustion or genital 
discomfort 
and sometimes even injury to himself and/or his partner before 
finally ceasing. Some males may report 
avoiding sexual 
activity because of a repetitive pattern of 
difficulty ejaculating. 


Delayed ejaculation is associated with highly frequent 
masturbation, use of masturbation 
techniques not 
easily duplicated by a partner, and marked disparities between sexual 
fantasies 
during masturbation and the reality of sex with a partner. 


Males with delayed ejaculation typically report 
less coital 
activity, higher levels of 
relationship distress, sexual 
dissatisfaction, lower subjective arousal, anxiety about 
their sexual 
performance, and general health issues than sexually functional men. 


In addition to considerations of applicable subtypes (i.e., whether the ejaculatory delay has 
been present 
since the individual 
became sexually active or began after a period of relatively 
normal 
sexual 
function, and whether the ejaculatory delay is generalized or occurs only with 
certain types of stimulation, situations, or partners), the following factors are important 
to 
consider in the assessment 
of delayed ejaculation: 
1) partner factors (e.g., partner s sexual 
problems or health); 2) relationship factors (e.g., poor communication, discrepancies 


480 


in desire for sexual 
activity); 
3) individual 
vulnerability factors (e.g., hypoactive sexual 
desire), psychiatric comorbidity (e.g., depression, anxiety), or stressors such as job loss or stress; 


4) cultural/religious factors (e.g., inhibitions related to prohibitions against 
sexual 
activity; 
attitudes toward sexuality); 
5) medical 
factors, particularly hypogonadism 
or neurological 
disorders (e.g., multiple sclerosis, diabetic neuropathy); 
and 6) use of substances or medications 
that might inhibit ejaculation (e.g., use of serotonergic drugs). 
Prevalence 


The prevalence of delayed ejaculation in the United States is estimated at 
1% 5% but 
has ranged 
as high as 11% in international 
studies. However, variation in syndrome definitions across 
studies may have contributed to differences in the prevalence of the DSM-5 disorder. 


Development and Course 



Lifelong delayed ejaculation begins with early sexual 
experiences and continues throughout 
the 
course of an individual s life. Acquired delayed ejaculation begins after a period of normal 
sexual 
function. A number of biomedical, psychosocial, and cultural 
factors can contribute to the 
predisposition to or maintenance of lifelong or acquired delayed ejaculation (see the section 
 Risk and Prognostic Factors ), and either subtype can be generalized or situational in nature. 


The prevalence of delayed ejaculation increases with age. As males age, they are more likely 
to have progressively more of the following changes in ejaculatory function, including, but 
not 
limited to, reduced ejaculatory volume, force, and sensation, and increased  refractory time.  
Refractory latency increases for males secondary to surgical, medical, and pharmaceutical 
complications, as well as aging. 


Risk and Prognostic Factors 


Ejaculatory latency is an end point 
consequence that 
is determined by a range of factors. A large 
number of psychosocial 
factors increase the probability of an individual 
experiencing delayed 
ejaculation, with depression and relationship dissatisfaction being predominant contributors. 


Genetic 
and 
physiological. 
Numerous medical 
conditions may lead to delayed ejaculation, 
including procedures that 
disrupt 
sympathetic or somatic innervation to the genital 
region such as 
radical 
prostatectomy for cancer treatment. Neurological 
and endocrine disorders, including 
spinal 
cord injury, stroke, multiple sclerosis, pelvic-region surgery, severe diabetes, epilepsy, 
hormonal 
abnormalities, and sleep apnea, as well 
as alcohol 
abuse, bowel 
dysfunction, cannabis 
use, and environmental factors, may be associated with delayed ejaculation. 


Additionally, medications that 
inhibit 
a-adrenergic innervation of the ejaculatory system 
(e.g., tamsulosin) are associated with delayed ejaculation, as well 
as antihypertensive agents, 
antidepressants (e.g., selective serotonin reuptake inhibitors), and antipsychotic drugs. 


Age-related loss of the fast-conducting peripheral 
sensory nerves and age-related decreased 
sex steroid secretion may be associated with an increase in delayed ejaculation in males as they 
age. Reduced androgen levels with age may also be associated with delayed ejaculation. 


Sex- and Gender-Related Diagnostic Issues 


By definition, the diagnosis of delayed ejaculation is only given to males. Distressing difficulties 
with orgasm in women would be considered under female orgasmic disorder. 


481 


Functional 
Consequences of Delayed Ejaculation 


Delayed ejaculation is often associated with considerable psychological 
distress in one or both 
partners. 


Difficulty with ejaculation may contribute to difficulties in conception and lead to significant 
fertility assessment, as the lack of ejaculation is not 
often spontaneously discussed by individuals 
unless there is direct inquiry from their physician. 


Differential 
Diagnosis 


Another medical 
condition 
or injury 
and/or its 
treatment. 
A major diagnostic challenge is 



differentiating between a delayed ejaculation that 
is fully explained by another medical 
condition 
or injury (or its treatment) and a delayed ejaculation attributable to a variety of proportionally 
different 
biomedical-psychosocial 
and cultural 
factors that 
determine the symptom(s). A number 
of medical 
conditions or injuries, along with their treatments, may produce delays in ejaculation 
independent of psychosocial and cultural issues. 


Delayed ejaculation must 
be differentiated from 
a number of urological 
conditions 
(especially other ejaculatory disorders), including retrograde ejaculation or anejaculation, which 
is typically the result 
of etiologies ranging from 
hormonal 
to neurological 
and/or anatomical 
abnormalities, including ejaculatory duct obstruction and other urological disorders. 


Substance/medication 
use. 
A number of pharmacological 
agents, such as antidepressants, 
antipsychotics, a 
sympathetic drugs, alcohol, and opioid drugs, can cause ejaculatory problems. 
In such cases, the diagnosis is substance/medication-induced sexual 
dysfunction instead of 
delayed ejaculation. 


Dysfunction 
with 
orgasm. 
It 
is important 
in the history to ascertain whether the complaint 
concerns 
delayed ejaculation or the sensation of orgasm, or both. Ejaculation occurs in the genitals, 
whereas the experience of orgasm 
is believed to be primarily subjective. Ejaculation and orgasm 
usually occur together but 
not 
always. For example, a male with a normal 
ejaculatory pattern 
may complain of decreased pleasure (i.e., anhedonic ejaculation). Such a complaint 
would not 
be 
coded as delayed ejaculation but 
could be coded as other specified sexual 
dysfunction or 
unspecified sexual dysfunction. 


Comorbidity 


There is some evidence to suggest 
that 
delayed ejaculation may be more common in severe 
forms of major depressive disorder. 


Erectile Disorder 


Diagnostic Criteria 
F52.21 


A. 
At 
least 
one 
of 
the 
three 
following 
symptoms must 
be 
experienced 
on 
almost 
all 
or all (approximately 75% 100%) occasions of 
sexual activity (in 
identified 
situational contexts or, 
if 
generalized, 
in 
all contexts): 
1. 
Marked 
difficulty in 
obtaining 
an 
erection 
during 
sexual activity. 
2. 
Marked 
difficulty in 
maintaining 
an 
erection 
until the 
completion 
of 
sexual 
activity. 
3. 
Marked 
decrease 
in 
erectile 
rigidity. 
B. 
The 
symptoms in 
Criterion 
A 
have 
persisted 
for a 
minimum duration 
of 
approximately 6 
months. 
C. 
The 
symptoms in 
Criterion 
A 
cause 
clinically significant 
distress in 
the 
individual. 
482 



D. 
The 
sexual dysfunction 
is not 
better explained 
by a 
nonsexual mental disorder or 
as a 
consequence 
of 
severe 
relationship 
distress or other significant 
stressors 
and 
is not 
attributable 
to 
the 
effects of 
a 
substance/medication 
or another 
medical condition. 
Specify 
whether: 


Lifelong: 
The 
disturbance 
has been 
present 
since 
the 
individual became 
sexually active. 
Acquired: 
The 
disturbance 
began 
after a 
period 
of 
relatively normal sexual 


function. 


Specify 
whether: 
Generalized: 
Not 
limited 
to 
certain 
types of 
stimulation, 
situations, 
or partners. 
Situational: 
Only occurs with 
certain 
types of 
stimulation, 
situations, 
or partners. 


Specify 
current 
severity: 
Mild: 
Evidence 
of 
mild 
distress over the 
symptoms in 
Criterion 
A. 
Moderate: 
Evidence 
of 
moderate 
distress over the 
symptoms in 
Criterion 
A. 
Severe: 
Evidence 
of 
severe 
or extreme 
distress over the 
symptoms in 
Criterion 


A. 


Diagnostic Features 


The essential 
feature of erectile disorder is a marked difficulty in obtaining or maintaining an 
erection or a marked decrease in erectile rigidity in all 
or almost 
all 
occasions of sexual 
activity 
(Criterion A) that 
has persisted for at 
least 
6 months (Criterion B) and that 
causes clinically 
significant 
distress in the individual 
(Criterion C). A careful 
sexual 
history is necessary to 
ascertain that 
the problem 
has been present 
for a significant 
duration of time (i.e., at 
least 
approximately 6 months) and occurs on the majority of sexual 
occasions (i.e., at 
least 
75% of the 
time). Symptoms may occur only in specific situations involving certain types of stimulation or 
partners, or they may occur in a generalized manner in all 
types of situations, stimulation, or 
partners. 


This chapter uses the terms erectile disorder 
and erectile dysfunction, which are not 
synonymous. Erectile dysfunction 
is a widely used descriptive term 
(including in ICD-10) that 
refers to difficulty getting and maintaining an erection. Erectile disorder 
is the more specific 
DSM-5 diagnostic category in which erectile dysfunction persists for at 
least 
6 months and 
causes distress in the individual. 


Associated Features 


Many males with erectile disorder may have low self-esteem, low self-confidence, and a 
decreased sense of masculinity, and may experience depressed mood. Erectile dysfunction is also 
strongly associated with feelings of guilt, self-blame, sense of failure, anger, and concern about 
disappointing one s partner. Fear and/or avoidance of future sexual 
encounters may occur. 
Decreased sexual satisfaction and reduced sexual desire in the individual s partner are common. 


In addition to considerations of applicable subtypes (i.e., whether the erectile dysfunction has 



been present 
since the individual 
became sexually active or began after a period of relatively 
normal 
sexual 
function, and whether the erectile dysfunction is generalized or occurs only with 
certain types of stimulation, situations, or partners), the following factors are important 
to 
consider in the assessment 
of erectile disorder: 
1) partner factors (e.g., partner s sexual 
problems 
or health); 
2) relationship factors (e.g., poor communication, discrepancies in desire for sexual 
activity); 
3) individual 
vulnerability factors (e.g., hypoactive sexual 
desire), psychiatric 
comorbidity (e.g., depression, anxiety), or stressors such as job loss or stress; 4) cultural/religious 
factors (e.g., inhibitions related to prohibitions against 
sexual 
activity; 
attitudes toward 
sexuality); 
5) medical 
factors, particularly surgery (e.g., transurethral 
resection of the prostate), 
hypogonadism, or neurological conditions 


483 


(e.g., multiple sclerosis, diabetic neuropathy); 
and 6) use of substances or medications that 
might inhibit ejaculation (e.g., use of serotonergic drugs). 


Prevalence 


The prevalence of lifelong versus acquired erectile disorder is unknown. There is a strong age-
related increase in both prevalence and incidence of problems with erection, particularly after 
age 50 years. Internationally, the prevalence of erectile disorder in the general 
population is 
approximately 13% 21% of males ages 40 80 years. Rates appear to be lower than 10% in 
males younger than 40 years, about 
20% 40% in males in their 60s, and 50% 75% in males 
older than 70 years. In a longitudinal 
study in Australia, 80% of males age 70 and older 
experienced erectile disorder. In a review of studies largely from 
Western countries, about 
20% 
of males feared erectile problems on their first 
sexual 
experience, whereas approximately 8% 
experienced erectile problems that 
hindered penetration during their first 
sexual 
experience. 
Among U.S.-based respondents to an online survey, there was no statistically significant 
difference in the prevalence of erectile disorder by ethnoracial 
background. Nationally 
representative U.S. data show that 
the prevalence of erectile difficulties is similar in older males 
who have sex with males or with both males and females. 


Development and Course 


Erectile failure on first 
sexual 
attempt 
has been found to be related to having sex with a 
previously unknown partner, concomitant 
use of drugs or alcohol, not 
wanting to have sex, and 
peer pressure. There is minimal 
evidence regarding the persistence of such problems after the 
first 
attempt. It 
is assumed that 
most 
of these problems spontaneously remit 
without 
professional 
intervention, but 
some males may continue to have episodic problems. In contrast, acquired 
erectile disorder is often associated with biological 
factors such as diabetes and cardiovascular 
disease. Acquired erectile disorder is likely to be persistent in most men. 


The natural 
history of lifelong erectile disorder is unknown. Clinical 
observation supports the 
association of lifelong erectile disorder with psychological 
factors that 
are self-limiting or 
responsive to psychological 
interventions, whereas, as noted above, acquired erectile disorder is 
more likely to be related to biological 
factors and to be persistent. The incidence of erectile 
disorder increases with age. A minority of males diagnosed as having moderate erectile failure 



may experience spontaneous remission of symptoms without 
medical 
intervention. Distress 
associated with erectile disorder is lower in older males as compared with younger males. 


Risk and Prognostic Factors 


Course 
modifiers. 
Risk factors for acquired erectile dysfunction and, as a consequence, erectile 
disorder include age, smoking tobacco, lack of physical exercise, diabetes, and decreased desire. 


Culture-Related Diagnostic Issues 


Prevalence of erectile disorder varies across countries. It 
is unclear to what 
extent 
these 
variations represent 
differences in cultural 
expectations as opposed to genuine differences in the 
frequency of erectile failure. Differential 
endorsement 
may be related to cultural 
concerns about 
appearing weak or less masculine or to diverse cultural 
norms about 
changes in erectile function 
during healthy aging. Cultural 
expectations concerning marital 
relationships, sexual 
performance, fertility, and gender roles can influence anxieties that 
may contribute to erectile 
disorder. Based on responses to an online survey, erectile disorder may be associated with 
concern about 
genital 
size in the United States and the Middle East 
and with fears of male 
infertility more frequently in the Middle East. 


484 


Sex- and Gender-Related Diagnostic Issues 


By definition, the diagnosis of erectile dysfunction is only given to males. Distressing difficulties 
with sexual arousal in women would be considered under female sexual interest/arousal disorder. 


Diagnostic Markers 


Nocturnal 
penile tumescence testing and measured erectile turgidity during sleep can be 
employed to help differentiate organic from 
psychogenic erectile problems on the assumption 
that 
adequate erections during rapid eye movement 
sleep indicate a psychological 
etiology to the 
problem. A number of other diagnostic procedures may be employed depending on the 
clinician s assessment 
of their relevance given the individual s age, comorbid medical 
problems, 
and clinical 
presentation. Doppler ultrasonography and intravascular injection of vasoactive 
drugs, as well 
as invasive diagnostic procedures such as dynamic infusion cavernosography, can 
be used to assess vascular integrity. Pudendal 
nerve conduction studies, including somatosensory 
evoked potentials, can be employed when a peripheral 
neuropathy is suspected. Testing for low 
levels of serum 
bioavailable or free testosterone is appropriate especially when diabetes is 
present, for men who also experience hypoactive desire, and for those who do not 
respond to 
phosphodiesterase type 5 inhibitors. Thyroid function may also be assessed. Determination of 
fasting serum 
glucose is useful 
to screen for the presence of diabetes mellitus. The assessment 
of 
serum 
lipids is important, as erectile disorder in males 40 years and older is predictive of the 
future risk for coronary artery disease. 


Association With Suicidal 
Thoughts or Behavior 


Among males receiving treatment 
for erectile disorder with comorbid depression, elevated rates 



of suicidal 
thoughts or behavior have been observed; 
while the affected males attributed the 
suicidal 
symptoms to their erectile disorder, the presence of depression was also a likely 
contributing factor. Elevated suicide rates among males with prostate cancer may in part 
be 
related to treatment-associated erectile dysfunction and consequent depressive symptoms. 


Functional 
Consequences of Erectile Disorder 


Erectile disorder can interfere with fertility and produce both individual 
and interpersonal 
distress. Fear and/or avoidance of sexual 
encounters may interfere with the ability to develop 
intimate relationships. Significant 
psychological 
distress may occur among males presenting 
with erectile disorder. 


Differential 
Diagnosis 


Nonsexual 
mental 
disorders. 
Major depressive disorder and erectile disorder are closely associated, 
and erectile disorder accompanying severe depressive disorder may occur. If the erectile 
difficulties are better explained by another mental 
disorder, such as major depression, then a 
diagnosis of erectile disorder would not be made. 


Normal 
erectile 
function. 


The differential 
should include consideration of normal 
erectile function 


in males with excessive expectations. 
Substance/medication 
use. 
An onset 
of erectile dysfunction that 
coincides with the beginning of 
substance/medication use and that 
dissipates with discontinuation of the substance/medication or 
dose reduction is suggestive of a substance/medication-induced sexual 
dysfunction, which 
should be diagnosed instead of erectile disorder. 


485 


Another medical 
condition. 
The most 
difficult 
aspect 
of the differential 
diagnosis of erectile 
disorder is ruling out 
erectile problems that 
are fully explained by medical 
factors. Such cases 
would not 
receive a diagnosis of a mental 
disorder. The distinction between erectile disorder as a 
mental 
disorder and erectile dysfunction as the result 
of another medical 
condition is usually 
unclear, and many cases will 
have complex, interactive biological 
and psychiatric etiologies. If 
the individual 
is older than 40 50 years and/or has concomitant 
medical 
problems, the 
differential 
diagnosis should include medical 
etiologies, especially vascular disease. The 
presence of an organic disease known to cause erectile problems does not 
confirm 
a causal 
relationship. For example, a male with diabetes mellitus can develop erectile disorder in response 
to psychological 
stress. In general, erectile dysfunction due to organic factors is generalized and 
gradual 
in onset. An exception would be erectile problems after traumatic injury to the nervous 
innervation of the genital 
organs (e.g., spinal 
cord injury). Erectile problems that 
are situational 
and inconsistent 
and that 
have an acute onset 
after a stressful 
life event 
are most 
often 
attributable to psychological 
events. An age younger than 40 years is also suggestive of a 
psychological etiology to the difficulty. 


Comorbidity 


Erectile disorder can be comorbid with other sexual 
diagnoses, such as premature (early) 



ejaculation and male hypoactive sexual 
desire disorder, as well 
as with anxiety and depressive 
disorders. The risk of depression is significantly higher in males with erectile disorder, with a 
markedly higher risk of depression in the first 
year after onset. In males diagnosed with 
posttraumatic stress disorder, erectile problems are common. Erectile disorder is common in 
males with lower urinary tract 
symptoms related to prostatic hypertrophy. Erectile disorder may 
be comorbid with dyslipidemia, cardiovascular disease, hypogonadism, multiple sclerosis, 
diabetes mellitus, and other diseases that 
interfere with the vascular, neurological, or endocrine 
function necessary for normal erectile function. 


Female Orgasmic Disorder 


Diagnostic Criteria 
F52.31 


A. 
Presence 
of 
either of 
the 
following 
symptoms and 
experienced 
on 
almost 
all or 
all (approximately 75% 100%) occasions of 
sexual activity (in 
identified 
situational contexts or, 
if 
generalized, 
in 
all contexts): 
1. 
Marked 
delay in, 
marked 
infrequency of, 
or absence 
of 
orgasm. 
2. 
Markedly reduced 
intensity of 
orgasmic sensations. 
B. 
The 
symptoms in 
Criterion 
A 
have 
persisted 
for a 
minimum duration 
of 
approximately 6 
months. 
C. 
The 
symptoms in 
Criterion 
A 
cause 
clinically significant 
distress in 
the 
individual. 
D. 
The 
sexual dysfunction 
is not 
better explained 
by a 
nonsexual mental disorder or 
as a 
consequence 
of 
severe 
relationship 
distress (e.g., 
partner violence) or other 
significant 
stressors and 
is not 
attributable 
to 
the 
effects of 
a 
substance/medication 
or another medical condition. 
Specify 
whether: 


Lifelong: 
The 
disturbance 
has been 
present 
since 
the 
individual became 
sexually active. 
Acquired: 
The 
disturbance 
began 
after a 
period 
of 
relatively normal sexual 


function. 


486 


Specify 
whether: 
Generalized: 
Not 
limited 
to 
certain 
types of 
stimulation, 
situations, 
or partners. 
Situational: 
Only occurs with 
certain 
types of 
stimulation, 
situations, 
or partners. 


Specify 
if: 


Never experienced 
an 
orgasm under any 
situation. 


Specify 
current 
severity: 
Mild: 
Evidence 
of 
mild 
distress over the 
symptoms in 
Criterion 
A. 



Moderate: 
Evidence 
of 
moderate 
distress over the 
symptoms in 
Criterion 
A. 
Severe: 
Evidence 
of 
severe 
or extreme 
distress over the 
symptoms in 
Criterion 
A. 


Diagnostic Features 


Female orgasmic disorder is characterized by difficulty experiencing orgasm 
and/or markedly 
reduced intensity of orgasmic sensations (Criterion A). Women show wide variability in the type 
or intensity of stimulation that 
elicits orgasm. Similarly, subjective descriptions of orgasm 
are 
extremely varied, suggesting that 
it 
is experienced in very different 
ways, both across women 
and on different 
occasions by the same woman. For a diagnosis of female orgasmic disorder, 
symptoms must 
be experienced on almost 
all 
or all 
(approximately 75% 100%) occasions of 
sexual 
activity (in identified situational 
contexts or, if generalized, in all 
contexts) and have a 
minimum 
duration of approximately 6 months. The use of the minimum 
severity and duration 
criteria is intended to distinguish transient 
orgasm 
difficulties from 
more persistent 
orgasmic 
dysfunction. The inclusion of  approximately  in Criterion B 
allows for clinician judgment 
in 
cases in which symptom duration does not meet the recommended 6-month threshold. 


For a woman to have a diagnosis of female orgasmic disorder, clinically significant 
distress 
must 
accompany the symptoms (Criterion C). In many cases of orgasm 
problems, the causes are 
multifactorial 
or cannot 
be determined. If female orgasmic disorder is deemed to be better 
explained by another mental 
disorder, the effects of a substance/medication, or a medical 
condition, then a diagnosis of female orgasmic disorder would not 
be made. Finally, if 
interpersonal 
or significant 
contextual 
factors, such as severe relationship distress, intimate 
partner violence, or other significant 
stressors, are present, then a diagnosis of female orgasmic 
disorder would not be made. 


Many women require clitoral 
stimulation to reach orgasm, and a relatively small 
proportion 
of women report 
that 
they always experience orgasm 
during penile-vaginal 
intercourse. Thus, a 
woman s experiencing orgasm 
through clitoral 
stimulation but 
not 
during intercourse does not 
meet 
criteria for a clinical 
diagnosis of female orgasmic disorder. It 
is also important 
to consider 
whether orgasm 
difficulties are the result 
of inadequate sexual 
stimulation; 
in these cases, there 
may still be a need for care, but a diagnosis of female orgasmic disorder would not be made. 


Associated Features 


Associations between specific patterns of personality traits or psychopathology and orgasmic 
dysfunction have generally not 
been supported. Compared with women without 
the disorder, 
some women with female orgasmic disorder may have greater difficulty communicating about 
sexual 
issues. Overall 
sexual 
satisfaction, however, is not 
strongly correlated with orgasmic 
experience. Many women report 
high levels of sexual 
satisfaction despite rarely or never 
experiencing orgasm. Orgasm 
difficulties in women often co-occur with problems related to 
sexual interest and arousal. 


In addition to the subtypes  lifelong/acquired  and  generalized/situational,  the following 
five factors must 
be considered during assessment 
and diagnosis of female orgasmic disorder 
given that 
they may be relevant 
to etiology or treatment: 
1) partner factors (e.g., partner s sexual 
problems, partner s health status); 2) relationship factors (e.g., poor 



487 


communication, discrepancies in desire for sexual 
activity); 
3) individual 
vulnerability 
factors (e.g., poor body image, history of sexual 
or emotional abuse), psychiatric comorbidity 
(e.g., depression, anxiety), or stressors (e.g., job loss, bereavement); 
4) cultural/religious factors 
(e.g., inhibitions related to prohibitions against 
sexual 
activity; 
attitudes toward sexuality); 
and 5) 
medical 
factors relevant 
to prognosis, course, or treatment. Each of these factors may contribute 
differently to the presenting symptoms of different women with this disorder. 


Prevalence 


Reported prevalence rates for orgasm 
problems in premenopausal 
women vary widely, from 
8% 
to 72%, depending on multiple factors (e.g., age, cultural 
background and context, duration, 
severity of symptoms); 
however, these estimates do not 
take into account 
the presence of 
distress. Only a proportion of women experiencing orgasm 
difficulties also report 
associated 
distress. Variation in how symptoms are assessed (e.g., the duration of symptoms and the recall 
period) also influence prevalence rates. Internationally, approximately 10% of women do not 
experience orgasm throughout their lifetime. 


Development and Course 


By definition, lifelong female orgasmic disorder indicates that 
the orgasm 
difficulties have 
always been present, whereas the acquired subtype would be assigned if the woman s orgasm 
difficulties developed after a period of normal orgasmic functioning. 


A woman s first 
experience of orgasm 
can occur any time from 
the prepubertal 
period to well 
into adulthood. Women show a more variable pattern in age at 
first 
orgasm 
than do men, and 
women s reports of having experienced orgasm 
increase with age. Many women learn to 
experience orgasm 
as they experience a wide variety of stimulation and acquire more knowledge 
about 
their bodies. Women s rates of orgasmic consistency (defined as  usually or always  
experiencing orgasm) are higher during masturbation than during sexual activity with a partner. 


Risk and Prognostic Factors 


Temperamental. 
A wide range of psychological 
factors, such as anxiety and concerns about 


pregnancy, can potentially interfere with a woman s ability to experience orgasm. 
Environmental. 
There is a strong association between relationship problems, physical 
health, and 
mental 
health and orgasm 
difficulties in women. Sociocultural 
factors (e.g., gender role 
expectations and religious norms) are also important 
influences on the experience of orgasm 
difficulties. 


Genetic 
and 
physiological. 
Many physiological 
factors may influence a woman s experience of 
orgasm, including medical 
conditions and medications. Conditions such as multiple sclerosis, 
pelvic nerve damage from 
radical 
hysterectomy, and spinal 
cord injury can all 
influence 
orgasmic functioning in women. Selective serotonin reuptake inhibitors are known to delay or 
inhibit 
orgasm 
in women. Women with vulvovaginal 
atrophy (characterized by symptoms such 
as vaginal 
dryness, itching, and pain) are significantly more likely to report 
orgasm 
difficulties 
than are women without 
this condition. Menopausal 
status is not 
consistently associated with the 



likelihood of orgasm 
difficulties. There may be a significant 
genetic contribution to variation in 
female orgasmic function. However, psychological, sociocultural, and physiological 
factors 
likely interact 
in complex ways to influence women s experience of orgasm 
and of orgasm 
difficulties. 


Culture-Related Diagnostic Issues 


The degree to which lack of orgasm 
in women is regarded as a problem 
that 
requires treatment 
may vary depending on cultural context. Cultural views that undervalue women s 


488 


sexual 
satisfaction or that 
perceive marital 
sex as a duty for women rather than a pleasurable 
activity are associated with lower help-seeking. In addition, women differ in how important 
orgasm 
is to their sexual 
satisfaction. There may be marked sociocultural 
and generational 
differences in women s orgasmic ability. For example, reports of the prevalence of inability to 
reach orgasm vary over a twofold range across world regions. 


Sex- and Gender-Related Diagnostic Issues 


By definition, the diagnosis of female orgasmic disorder is given only to women. Distressing 
difficulties with orgasm in men would be considered under delayed ejaculation. 


Diagnostic Markers 


Although measurable physiological 
changes occur during female orgasm, including changes in 
hormones, pelvic floor musculature, and brain activation, there is significant 
variability in these 
indicators of orgasm 
across women. In clinical 
situations, the diagnosis of female orgasmic 
disorder is based on a woman s self-report. 


Association With Suicidal 
Thoughts or Behavior 


Dysfunctions of sexual 
arousal 
and satisfaction have been associated with suicidal 
thoughts 
among female veterans and military service members even after adjustment 
for probable 
posttraumatic stress disorder, probable depression, history of deployment, married status, age, 
service in the army, and race. 


Functional 
Consequences of Female Orgasmic Disorder 


The functional 
consequences of female orgasmic disorder are unclear. Although there is a strong 
association between relationship problems and orgasm 
difficulties in women, it 
is unclear 
whether relationship factors are risk factors for orgasm 
difficulties or are consequences of those 
difficulties. 


Differential 
Diagnosis 


Nonsexual 
mental 
disorders. 
If the orgasm 
difficulties are better explained by another mental 
disorder, such as major depression, then a diagnosis of female orgasmic disorder would not 
be 
made. 



Substance/medication-induced 
sexual 
dysfunction. 
An onset 
of orgasmic dysfunction that 
coincides 
with the beginning of substance/medication use and that 
dissipates with discontinuation of the 


substance/medication or dose reduction is suggestive of a substance/medication-induced sexual 
dysfunction, which should be diagnosed instead of female orgasmic disorder. 
Another medical 
condition. 
If the disorder is attributable to another medical 
condition (e.g., 


multiple sclerosis, spinal 
cord injury), then a diagnosis of female orgasmic disorder would not 
be 


made. 
Interpersonal 
factors. 
If interpersonal 
or significant 
contextual 
factors, such as severe relationship 
distress, intimate partner violence, or other significant 
stressors, are associated with the orgasm 
difficulties, then a diagnosis of female orgasmic disorder would not be made. 


Other sexual 
dysfunctions. 
Female orgasmic disorder may occur in association with other sexual 
dysfunctions (e.g., female sexual 
interest/arousal 
disorder). The presence of another sexual 
dysfunction does not 
rule out 
a diagnosis of female orgasmic disorder. Occasional 
orgasm 
difficulties that 
are short-term 
or infrequent 
and are not 
accompanied by clinically significant 
distress or impairment 
are not 
diagnosed as female orgasmic disorder. A diagnosis is also not 
appropriate if the problems are the result of inadequate sexual stimulation. 


489 


Comorbidity 


Women with female orgasmic disorder may have co-occurring sexual 
interest/arousal 
difficulties. Women with diagnoses of other nonsexual 
mental 
disorders, such as major 
depressive disorder, may experience lower sexual 
interest/arousal, and this may indirectly 
increase the likelihood of orgasm difficulties. 


Female Sexual 
Interest/Arousal 
Disorder 


Diagnostic Criteria 
F52.22 


A. 
Lack of, 
or significantly reduced, 
sexual interest/arousal, 
as manifested 
by at 
least 
three 
of 
the 
following: 
1. 
Absent/reduced 
interest 
in 
sexual activity. 
2. 
Absent/reduced 
sexual/erotic thoughts or fantasies. 
3. 
No/reduced 
initiation 
of 
sexual activity, 
and 
typically unreceptive 
to 
a 
partner s 
attempts to 
initiate. 
4. 
Absent/reduced 
sexual excitement/pleasure 
during 
sexual activity in 
almost 
all or all (approximately 75% 100%) sexual encounters (in 
identified 
situational contexts or, 
if 
generalized, 
in 
all contexts). 
5. 
Absent/reduced 
sexual interest/arousal in 
response 
to 
any internal or external 
sexual/erotic cues (e.g., 
written, 
verbal, 
visual). 
6. 
Absent/reduced 
genital or nongenital sensations during 
sexual activity in 

almost 
all or all (approximately 75% 100%) sexual encounters (in 
identified 
situational contexts or, 
if 
generalized, 
in 
all contexts). 


B. 
The 
symptoms in 
Criterion 
A 
have 
persisted 
for a 
minimum duration 
of 
approximately 6 
months. 
C. 
The 
symptoms in 
Criterion 
A 
cause 
clinically significant 
distress in 
the 
individual. 
D. 
The 
sexual dysfunction 
is not 
better explained 
by a 
nonsexual mental disorder or 
as a 
consequence 
of 
severe 
relationship 
distress (e.g., 
partner violence) or other 
significant 
stressors and 
is not 
attributable 
to 
the 
effects of 
a 
substance/medication 
or another medical condition. 
Specify 
whether: 


Lifelong: 
The 
disturbance 
has been 
present 
since 
the 
individual became 
sexually active. 
Acquired: 
The 
disturbance 
began 
after a 
period 
of 
relatively normal sexual 


function. 


Specify 
whether: 
Generalized: 
Not 
limited 
to 
certain 
types of 
stimulation, 
situations, 
or partners. 
Situational: 
Only occurs with 
certain 
types of 
stimulation, 
situations, 
or partners. 


Specify 
current 
severity: 
Mild: 
Evidence 
of 
mild 
distress over the 
symptoms in 
Criterion 
A. 
Moderate: 
Evidence 
of 
moderate 
distress over the 
symptoms in 
Criterion 
A. 
Severe: 
Evidence 
of 
severe 
or extreme 
distress over the 
symptoms in 
Criterion 


A. 


Diagnostic Features 


In assessing female sexual 
interest/arousal 
disorder, interpersonal 
context 
must 
be taken into 
account. A  desire discrepancy,  in which a woman has lower desire for sexual 
activity than her 
partner, is not 
sufficient 
to diagnose female sexual 
interest/arousal 
disorder. For the criteria for 
the disorder to be met, there must be absence or reduced frequency or 


490 


intensity of at 
least 
three of six indicators (Criterion A) for a minimum 
duration of approximately 
6 months (Criterion B). There may be different 
symptom 
profiles across women, as well 
as 
variability in how sexual 
interest 
and arousal 
are expressed. For example, in one woman, sexual 
interest/arousal 
disorder may be 
expressed as a lack of interest 
in sexual 
activity, an absence of 
erotic or sexual 
thoughts, and reluctance to initiate sexual 
activity and respond to a partner s 
sexual 
invitations. In another woman, an inability to become sexually excited, an inability to 
respond to sexual 
stimuli 
with sexual 
desire, and a corresponding lack of signs of physical 
sexual 
arousal 
may be the primary features. Difficulties in desire and sexual 
arousal 
may also occur 
simultaneously, as women with loss of sexual 
desire may be nine times more likely to also have 
lost 
sexual 
excitement 
or arousal. Short-term 
changes in sexual 
interest 
or arousal 
are common 



and may be adaptive responses to events in a woman s life and do not 
represent 
a sexual 
dysfunction. Diagnosis of female sexual 
interest/arousal 
disorder requires a minimum 
duration of 
symptoms of approximately 6 months as a reflection that 
the symptoms must 
be a persistent 
problem. The estimation of persistence may be determined by clinical 
judgment 
when a duration 
of 6 months cannot be ascertained precisely. 


There may be absent 
or reduced frequency or intensity of interest 
in sexual 
activity (Criterion 
A1), which was previously the single criterion for hypoactive sexual 
desire disorder; 
this 
condition is now represented by female sexual 
interest/arousal 
disorder. The frequency or 
intensity of sexual 
and erotic thoughts or fantasies may be absent 
or reduced (Criterion A2). The 
expression of fantasies varies widely across women and may include memories of past 
sexual 
experiences. The normative decline in sexual 
thoughts with age should be taken into account 
when this criterion is being assessed. Absence or reduced frequency of initiating sexual 
activity 
and of receptivity to a partner s sexual 
invitations (Criterion A3) is a behaviorally focused 
criterion. A couple s beliefs and preferences for sexual 
initiation patterns are highly relevant 
to 
the assessment 
of this criterion. There may be absent 
or reduced sexual 
excitement 
or pleasure 
during sexual 
activity in almost 
all 
or all 
(approximately 75% 100%) sexual 
encounters 
(Criterion A4). Lack of pleasure is a common presenting clinical 
complaint 
in women with low 
desire. Among women who report 
low sexual 
desire, there are fewer sexual 
or erotic cues that 
elicit 
sexual 
interest 
or arousal 
(i.e., there is a lack of  responsive desire ). Evidence suggests 
that 
there may be at 
least 
two types of female sexual 
interest/arousal 
disorder: 
one based on low 
sensitivity to sexual 
cues and a second based on overactivation of sexual 
inhibition. Assessment 
of the adequacy of sexual 
stimuli 
will 
assist 
in determining if there is a difficulty with responsive 
sexual 
desire (Criterion A5). Frequency or intensity of genital 
or nongenital 
sensations during 
sexual 
activity may be reduced or absent 
(Criterion A6). This may include reduced vaginal 
lubrication/vasocongestion, but 
because physiological 
measures of genital 
sexual 
response do not 
differentiate women who report 
sexual 
arousal 
concerns from 
those who do not, the self-report 
of 
reduced or absent genital or nongenital sensations is sufficient. 


For a diagnosis of female sexual 
interest/arousal 
disorder to be 
made, clinically significant 
distress must accompany the symptoms in Criterion A. Distress may be experienced as a result of 
the lack of sexual 
interest/arousal 
or as a result 
of significant 
interference in a woman s life and 
well-being. If a lifelong lack of sexual 
desire is better explained by one s self-identification as 
 asexual,  then a diagnosis of female sexual interest/arousal disorder would not be made. 


Associated Features 


Female sexual 
interest/arousal 
disorder is frequently associated with problems in experiencing 
orgasm, pain experienced during sexual 
activity, infrequent 
sexual 
activity, and couple-level 
discrepancies in desire. Relationship difficulties, chronic stress, and mood disorders are also 
frequently associated features of female sexual 
interest/arousal 
disorder. Unrealistic expectations 
and norms regarding the  appropriate  level of sexual 


491 


interest 
or arousal, along with poor sexual 
techniques and lack of information about 
sexuality, 
may also be evident 
in women diagnosed with female sexual 
interest/arousal 
disorder. The latter, 



as well as normative beliefs about gender roles, are important factors to consider. 


In addition to the subtypes  lifelong/acquired  and  generalized/situational,  the following 
five factors must be considered during assessment and diagnosis of female sexual interest/arousal 
disorder given that 
they may be relevant 
to etiology and/or treatment: 
1) partner factors (e.g., 
partner s sexual 
problems, partner s health status, partner-related distress); 
2) relationship factors 
(e.g., poor communication, discrepancies in desire for sexual 
activity; 
relationship duration); 
3) 
individual 
vulnerability factors (e.g., poor body image, history of sexual 
or emotional 
abuse), 
psychiatric comorbidity (e.g., depression, anxiety), or stressors (e.g., job loss, bereavement); 
4) 
cultural/religious factors (e.g., inhibitions related to prohibitions against 
sexual 
activity; 
attitudes 
toward sexuality); 
and 5) medical 
factors relevant 
to prognosis, course, or treatment. Note that 
each of these factors may contribute differently to the presenting symptoms of different 
women 
with this disorder. 


Prevalence 


Approximately 30% of women experience chronic low desire, with approximately half of these 
experiencing significant 
partner-related distress and a quarter experiencing personal 
distress. The 
prevalence of low sexual 
desire and of problems with sexual 
arousal 
(with and without 
associated distress) may vary markedly in relation to age, cultural context, duration of symptoms, 
and presence of distress. Regarding duration of symptoms, there are striking differences in 
prevalence estimates between short-term 
and persistent 
problems related to lack of sexual 
interest. When distress about 
sexual 
functioning is required, prevalence estimates are markedly 
lower. Though there is a strong relationship between low desire and age, the prevalence of sex-
related distress associated with low desire decreases as women age. 


Development and Course 


By definition, lifelong female sexual 
interest/arousal 
disorder suggests that 
the lack of sexual 
interest 
or arousal 
has been present 
for the woman s entire sexual 
life. For Criteria A3, A4, and 
A6, which assess functioning during sexual 
activity, a subtype of lifelong would mean presence 
of symptoms since the individual s first 
sexual 
experiences. The acquired subtype would be 
assigned if the difficulties with sexual 
interest 
or arousal 
developed after a period of 
nonproblematic sexual 
functioning. Adaptive and normative changes in sexual 
functioning may 
result 
from 
partner-related, interpersonal, or personal 
events and may be transient 
in nature. 
However, persistence of symptoms for approximately 6 months or more would constitute a 
sexual dysfunction. 


There are normative changes in sexual 
interest 
and arousal 
across the life span. Furthermore, 
women in relationships of longer duration are more likely to report 
engaging in sex despite no 
obvious feelings of sexual 
desire at 
the outset 
of a sexual 
encounter compared with women in 
shorter-duration relationships. Vaginal 
dryness in older women is related to age and menopausal 
status. 


Risk and Prognostic Factors 


Temperamental. 
Temperamental 
factors include negative cognitions and attitudes about 
sexuality 
and past 
history of mental 
disorders. Differences in propensity for sexual 
excitation and sexual 



inhibition may also predict the likelihood of developing sexual problems. 
Environmental. 
Environmental 
factors include relationship difficulties, partner sexual 
functioning, and developmental 
history, such as early relationships with caregivers and 
childhood stressors. 


492 


Genetic 
and 
physiological. 
Some medical 
conditions (e.g., diabetes mellitus, thyroid dysfunction) 
can be risk factors for female sexual 
interest/arousal 
disorder. There appears to be a strong 
influence of genetic factors on vulnerability to sexual 
problems in women. Psychophysiological 
research using vaginal 
photoplethysmography has not 
found differences between women with 
and without perceived lack of genital arousal. 


Culture-Related Diagnostic Issues 


There is marked variability in reported prevalence rates of low desire across world regions, 
ranging from 
26% to 43%. Low levels of sexual 
desire have been reported by some ethnoracial 
and migrant 
groups. Although lower levels of reported sexual 
desire and arousal 
may reflect 
less 
interest 
in sex, such group differences may be an artifact 
of the measures used to quantify desire 
and of cultural 
factors affecting response, such as the desirability of reporting sexual 
activity by 
nonmarried, menopausal, or widowed women. A judgment 
about 
whether low sexual 
desire 
reported by a woman from 
a certain ethnocultural 
background meets criteria for female sexual 
interest/arousal 
disorder must 
take into account 
the fact 
that 
different 
cultural 
groups may vary in 
norms and expectations for sexual behavior. 


Sex- and Gender-Related Diagnostic Issues 


By definition, the diagnosis of female sexual 
interest/arousal 
disorder is only given to women. 
Distressing difficulties with sexual 
desire in men would be considered under male hypoactive 
sexual 
desire disorder. There are no data showing that 
rates or expressions of female sexual 
interest/arousal disorder differ between heterosexual and lesbian women. 


Association With Suicidal 
Thoughts or Behavior 


Dysfunctions of sexual 
arousal 
and satisfaction have been associated with suicidal 
thoughts 
among female veterans and military service members even after adjustment 
for probable PTSD, 
probable depression, history of deployment, married status, age, service in the army, and race. 


Functional 
Consequences of Female Sexual 
Interest/Arousal 
Disorder 


Difficulties in sexual 
interest/arousal 
are often associated with decreased relationship 
satisfaction. 


Differential 
Diagnosis 


Nonsexual 
mental 
disorders. 
Nonsexual 
mental 
disorders, such as major depressive disorder, in 
which there is  markedly diminished interest 
or pleasure in all, or almost 
all, activities most 
of 
the day, nearly every day,  may explain the lack of sexual 
interest/arousal. If the lack of interest 



or arousal 
is completely attributable to another mental 
disorder, then a diagnosis of female sexual 
interest/arousal disorder would not be made. 


Substance/medication 
use. 


An onset 
of difficulties in desire or arousal 
that 
coincides with the 
beginning of substance/medication use and that 
dissipates with discontinuation of the 
substance/medication or dose reduction is suggestive of a substance/medication-induced sexual 
dysfunction, which should be diagnosed instead of female sexual interest/arousal disorder. 


Another medical 
condition. 
If the sexual 
symptoms are considered to be almost 
exclusively 
associated with the effects of another medical condition (e.g., diabetes mellitus, 


493 


endothelial 
disease, thyroid dysfunction, central 
nervous system 
disease), then a diagnosis of 


female sexual interest/arousal disorder would not be made. 
Interpersonal 
factors. 
If interpersonal 
or significant 
contextual 
factors, such as severe relationship 
distress, intimate partner violence, or other significant 
stressors, explain the sexual 
interest/arousal 
symptoms, then a diagnosis of female sexual 
interest/arousal 
disorder would not 
be made. 


Other sexual 
dysfunctions. 
The presence of another sexual 
dysfunction does not 
rule out 
a 
diagnosis of female sexual 
interest/arousal 
disorder. It 
is common for women to experience more 
than one sexual dysfunction. For example, the presence of chronic genital pain may lead to a lack 
of desire for the (painful) sexual 
activity. Lack of interest 
and arousal 
during sexual 
activity may 
impair orgasmic ability. For some women, all 
aspects of the sexual 
response may be unsatisfying 
and distressing. 


Inadequate 
or absent 
sexual 
stimuli. 
When differential 
diagnoses are being considered, it 
is 
important 
to assess the adequacy of sexual 
stimuli 
within the woman s sexual 
experience. In 
cases where inadequate or absent 
sexual 
stimuli 
are contributing to the clinical 
picture, there may 
be evidence for clinical 
care, but 
a sexual 
dysfunction diagnosis would not 
be made. Similarly, 
transient 
and adaptive alterations in sexual 
functioning that 
are secondary to a significant 
life or 
personal event must be considered in the differential diagnosis. 


Comorbidity 


Comorbidity between sexual 
interest/arousal 
problems and other sexual 
difficulties is extremely 
common. Sexual 
distress and dissatisfaction with sex life are also highly correlated in women 
with low sexual 
desire. Distressing low desire is associated with depression, thyroid problems, 
anxiety, urinary incontinence, and other medical 
factors. Arthritis and inflammatory or irritable 
bowel 
disease are also associated with sexual 
arousal 
problems. Low desire appears to be 
comorbid with depression, sexual and physical abuse in adulthood, and use of alcohol. 


Genito-Pelvic Pain/Penetration 
Disorder 


F52.6Diagnostic Criteria

A. 
Persistent 
or recurrent 
difficulties with 
one 
(or more) of 
the 
following: 
1. 
Vaginal penetration 
during 
intercourse. 
2. 
Marked 
vulvovaginal or pelvic pain 
during 
vaginal intercourse 
or penetration 
attempts. 
3. 
Marked 
fear or anxiety about 
vulvovaginal or pelvic pain 
in 
anticipation 
of, 
during, 
or as a 
result 
of 
vaginal penetration. 
4. 
Marked 
tensing 
or tightening 
of 
the 
pelvic floor muscles during 
attempted 
vaginal penetration. 
B. 
The 
symptoms in 
Criterion 
A 
have 
persisted 
for a 
minimum duration 
of 
approximately 6 
months. 
C. 
The 
symptoms in 
Criterion 
A 
cause 
clinically significant 
distress in 
the 
individual. 
D. 
The 
sexual dysfunction 
is not 
better explained 
by a 
nonsexual mental disorder or 
as a 
consequence 
of 
a 
severe 
relationship 
distress (e.g., 
partner violence) or 
other significant 
stressors and 
is not 
attributable 
to 
the 
effects of 
a 
substance/medication 
or another medical condition. 
494 


Specify 
whether: 


Lifelong: 
The 
disturbance 
has been 
present 
since 
the 
individual became 
sexually active. 
Acquired: 
The 
disturbance 
began 
after a 
period 
of 
relatively normal sexual 


function. 


Specify 
current 
severity: 
Mild: 
Evidence 
of 
mild 
distress over the 
symptoms in 
Criterion 
A. 
Moderate: 
Evidence 
of 
moderate 
distress over the 
symptoms in 
Criterion 
A. 
Severe: 
Evidence 
of 
severe 
or extreme 
distress over the 
symptoms in 
Criterion 


A. 


Diagnostic Features 


Genito-pelvic pain/penetration disorder refers to four commonly comorbid symptom 
dimensions: 


1) difficulty having intercourse, 2) genito-pelvic pain, 3) fear of pain or vaginal 
penetration, and 
4) tension of the pelvic floor muscles (Criterion A). Because major difficulty in any one of these 
symptom 
dimensions is often sufficient 
to cause clinically significant 
distress, a diagnosis can be 
made on the basis of marked difficulty in only one symptom 
dimension. However, all 
four 
symptom 
dimensions should be assessed even if a diagnosis can be made on the basis of only 
one symptom dimension. 
Marked difficulty having vaginal intercourse/penetration 
(Criterion A1) can vary from 
a total 
inability to experience vaginal 
penetration in any situation (e.g., intercourse, gynecological 
examinations, tampon insertion) to the ability to easily experience penetration in one situation 
but 
not 
in another. Although the most 
common clinical 
situation is when a female is unable to 



experience intercourse or penetration with a partner, difficulties in undergoing required 
gynecological 
examinations may also be present. Marked vulvovaginal 
or pelvic pain during 
vaginal 
intercourse or penetration attempts 
(Criterion A2) refers to pain occurring in different 
locations in the genito-pelvic area. Location of pain as well 
as intensity should be assessed. 
Typically, pain can be characterized as superficial 
(vulvovaginal 
or occurring during penetration) 
or deep (pelvic; 
i.e., not 
felt 
until 
deeper penetration). The intensity of the pain is often not 
linearly related to distress or interference with vaginal 
penetration or other sexual 
activities. 
Some genito-pelvic pain only occurs when provoked (i.e., by intercourse or mechanical 
stimulation); 
other genito-pelvic pain may be spontaneous as well 
as provoked. Genito-pelvic 
pain can also be usefully characterized qualitatively (e.g.,  burning,   cutting,   shooting,  
 throbbing ). The pain may persist for a period after intercourse is completed and may also occur 
during urination. Typically, the pain experienced during vaginal 
intercourse can be reproduced 
during a gynecological examination. 


Marked fear or anxiety about 
vulvovaginal 
or pelvic pain either in anticipation of, or during, 
or as a result 
of 
vaginal 
penetration 
(Criterion A3) is commonly reported by females who have 
regularly experienced pain during vaginal 
penetration. This  normal  reaction may lead to 
avoidance of sexual/intimate situations. In other cases, this marked fear does not 
appear to be 
closely related to the experience of pain but 
nonetheless leads to avoidance of intercourse and 
vaginal 
penetration situations. Some have described this as similar to a phobic reaction except 
that the phobic object may be vaginal penetration or the fear of pain. 


Marked tensing or tightening of 
the pelvic floor muscles during attempted vaginal 
penetration 
(Criterion A4) can vary from 
reflexive-like spasm 
of the pelvic floor in response to 
attempted vaginal 
entry to  normal/voluntary  muscle guarding in response to the anticipated or 
the repeated experience of pain or to fear or anxiety. In the case of  normal/guarding  reactions, 
penetration may be possible under circumstances of relaxation. The characterization and 
assessment 
of pelvic floor dysfunction is often best 
undertaken by a specialist 
gynecologist 
or by 
a pelvic floor physical therapist. 


Symptoms of genito-pelvic pain/penetration disorder may be characterized by previous 
terms, including dyspareunia (pain during sexual intercourse) and vaginismus (defined by 


495 


involuntary contraction of muscles making penetration painful 
or impossible). Specific 
medical 
disorders, such as vulvodynia (chronic idiopathic vulvar pain lasting at 
least 
3 months) 
and provoked vestibulodynia (contact-induced vulvodynia localized to the vulvar vestibule), may 
be a primary cause of genito-pelvic pain/penetration disorder and may be a focus in studies of the 
disorder. Females diagnosed with these other conditions report 
significant 
distress, and their 
symptoms are likely to meet criteria for genito-pelvic pain/penetration disorder. 


Associated Features 


Genito-pelvic pain/penetration disorder is frequently associated with other sexual 
dysfunctions, 
particularly reduced sexual 
desire and interest 
(female sexual 
interest/arousal 
disorder). 
Sometimes desire and interest 
are preserved in sexual 
situations that 
are not 
painful 
or do not 
require penetration. Even when individuals with genito-pelvic pain/penetration disorder report 



sexual 
interest/motivation, there is often behavioral 
avoidance of sexual 
situations and 
opportunities. Avoidance of gynecological 
examinations despite medical 
recommendations is 
also frequent. The pattern of avoidance is similar to that 
seen in phobic disorders. It 
is common 
for females who have not 
succeeded in having vaginal 
penetration to come for treatment 
only 
when they wish to conceive. Many females with genito-pelvic pain/penetration disorder will 
experience associated relationship/marital 
problems; 
they also often report 
that 
the symptoms 
significantly diminish their feelings of femininity. 


In addition to the subtype  lifelong/acquired,  five factors should be considered during 
assessment 
and diagnosis of genito-pelvic pain/penetration disorder because they may be 
relevant 
to etiology or treatment: 
1) partner factors (e.g., partner s sexual 
problems, partner s 
health status); 
2) relationship factors (e.g., partner responses to the pain, including solicitous, 
negative, and facilitative responses; 
discrepancies in desire for sexual 
activity); 
3) individual 
vulnerability factors (e.g., poor body image, history of sexual 
or emotional 
abuse), psychiatric 
comorbidity (e.g., depression, anxiety), or stressors (e.g., job loss, bereavement); 
4) 
cultural/religious factors (e.g., inhibitions related to prohibitions against 
sexual 
activity; 
attitudes 
toward sexuality); 
and 5) medical 
factors relevant 
to prognosis, course, or treatment. Each of 
these factors may contribute differently to the presenting symptoms of different 
females with this 
disorder. 


Prevalence 


The prevalence of genito-pelvic pain/penetration disorder is unknown. However, approximately 
10% 28% of females of reproductive age in the United States report 
recurrent 
pain during 
intercourse. Difficulties having intercourse appear to be a frequent 
referral 
to sexual 
dysfunction 
clinics and to specialist 
clinicians. Internationally, prevalence of genito-pelvic pain upon 
intercourse ranges from 8% to 28% among females of reproductive age and varies by country. 


Prevalence of genito-pelvic pain during sexual activities involving vaginal penetration among 
lesbian women relative to heterosexual 
women remains uncertain but 
may be similar or lower. 
Prevalence rates among other sexual minorities, including transgender women, are unknown. 


Development and Course 


The development 
and course of genito-pelvic pain/penetration disorder is unclear. Because 
women generally do not 
seek treatment 
until 
they experience problems in sexual 
functioning, it 
can, in general, be difficult 
to characterize genito-pelvic pain/penetration disorder as lifelong 
(primary) or acquired (secondary). Although women typically come to clinical 
attention after the 
initiation of sexual 
activity, there are often earlier clinical 
signs. For example, difficulty with or 
the avoidance of use of tampons is an important predictor of later 


496 


problems. Difficulties with vaginal 
penetration (inability or fear or pain) may not 
be obvious 
until 
intercourse is attempted during sexual 
activity. Even once intercourse is attempted, the 
frequency of attempts may not 
be significant 
or regular. In cases where it 
is difficult 
to establish 
whether symptomatology is lifelong or acquired, it 
is useful 
to determine the presence of any 
consistent period of successful pain-, fear-, and tension-free intercourse. If the experience of such 



a period can be established, then genito-pelvic pain/penetration disorder can be characterized as 
acquired. Once symptomatology is present 
for a period of approximately 6 months, the 
probability of spontaneous and significant symptomatic remission appears to diminish. 


Complaints related to genito-pelvic pain peak during early adulthood and in the peri- and 
postmenopausal 
period. There may also be an increase in genito-pelvic pain related symptoms in 
the postpartum period. 


Risk and Prognostic Factors 


Temperamental. 
Females with antecedent 
mood and anxiety disorders are four times more likely 
to develop symptoms of genito-pelvic pain/penetration disorder compared with those without 
these antecedent 
disorders. Psychosocial 
factors (e.g., pain catastrophizing, pain self-efficacy, 
avoidance of pain, negative mood) and interpersonal 
factors (e.g., insecure attachment, negative 
partner responses to the pain, sexual 
motives that 
focus on avoiding negative relationship 
outcomes) may exacerbate and maintain symptoms. 


Environmental. 
Females with genito-pelvic pain/penetration disorder are more likely to report 
a 
history of sexual 
and/or physical 
abuse, and fear of abuse than females without 
this disorder, 
although not all women with presenting symptoms have this history. 


Genetic 
and 
physiological. 
Females experiencing superficial 
pain during vaginal 
penetration often 
report 
the onset 
of the pain after a history of vaginal 
infections. Even after the infections have 
resolved and there are no known residual 
physical 
findings, the pain persists. Pain during tampon 
insertion or the inability to insert 
tampons before any sexual 
contact 
has been attempted is an 
important risk factor for genito-pelvic pain/penetration disorder. 


Additional 
biomedical 
risk factors include early puberty, inflammation, early use of oral 
contraceptives, vulvar pain receptor proliferation (i.e., increase 
in the number of receptors) and 
sensitization (i.e., touch may become perceived as pain), and lower touch and pain thresholds. 
Abnormalities of the pelvic floor muscles while at 
rest, including hypertonicity, poor muscle 
control, hypersensitivity, and altered contractility, may close the vaginal 
hiatus and interfere with 
penetration. 


Culture-Related Diagnostic Issues 


Cultural 
contexts can affect 
the experience and reporting of genito-pelvic pain related to 
intercourse. Affected females experience negative implications related to social 
narratives of 
womanhood, sexuality, and femininity, including pressures to prioritize men s sexual 
desire and 
penetrative sex, and depictions of sex as easy and natural. Cultural 
views that 
devalue female 
sexual 
experience may affect 
the way women interpret 
the experience of pain during sex, their 
help-seeking choices, and how they discuss their symptoms with their caregivers. For example, 
some females may not 
report 
genito-pelvic pain specifically but 
rather refer to being unhappy in 
their marriages. 


In the United States, Hispanic females endorse significantly higher rates of genito-pelvic pain 
and are more likely to report 
pain with first 
intercourse (i.e., primary genito-pelvic 
pain/penetration disorder) compared with non-Hispanic women. In a Minneapolis, Minnesota 
survey, only about 
half of females with genito-pelvic pain sought 
treatment, and those who did 
frequently reported feeling stigmatized. Such experiences may be heightened for 



497 


sexual 
minorities and underserved ethnic and racialized groups, especially given evidence of 
inequities in pain treatment for females and African Americans. 


Sex- and Gender-Related Diagnostic Issues 


Gendered social 
constructions relating to womanhood and femininity are implicated in the 
experience of genito-pelvic pain/penetration disorder, including the prioritization of both 
penetrative sex and men s sexual 
desires above women s own needs and desires. The disorder is 
associated with feelings of shame and inadequacy as a female, contributing further to enhanced 
psychological distress. 


By definition, the diagnosis of genito-pelvic pain/penetration disorder is only given to 
females. There is relatively new research concerning urological 
chronic pelvic pain syndrome in 
males, suggesting that 
males may experience some similar problems. The prevalence of male 
genito-pelvic pain is estimated to be 2.2% 9.7% worldwide. The research and clinical experience 
are not 
sufficiently developed yet 
to justify the application of this diagnosis to males. Other 
specified sexual 
dysfunction or unspecified sexual 
dysfunction may be diagnosed in males 
appearing to fit this pattern. 


Diagnostic Markers 


Validated physiological 
measures of Criterion A2 symptoms (Marked vulvovaginal 
or pelvic 
pain during vaginal 
intercourse or penetration attempts) can be assessed in real 
time (e.g., the 
cotton-swab test, vulvalgesiometer, tampon test). Although these measures are well 
validated for 
pain intensity during penetration attempts, none approximate the sexual context in which the pain 
is experienced, which can only be assessed via self-report. Criterion A4 symptoms (Marked 
tensing or tightening of 
the pelvic floor muscles during attempted vaginal 
penetration) can also 
be measured (e.g., via electromyographic amplitude, dynamometer, 4D ultrasound by a qualified 
physical 
therapist). There are no validated physiological 
measures of component 
symptoms for 
Criterion A1 or A3. Validated psychometric inventories may be used to formally assess the pain 
and anxiety components related to genito-pelvic pain/penetration disorder. 


Functional 
Consequences of Genito-Pelvic Pain/Penetration Disorder 


Functional 
difficulties in genito-pelvic pain/penetration disorder are often associated with 
interference in various aspects of the romantic relationship including the initiation of such 
relationships and sometimes with the ability to conceive via penile/vaginal intercourse. 


Differential 
Diagnosis 


Another medical 
condition. 
In many instances, females with genito-pelvic pain/penetration 
disorder will 
also be diagnosed with another medical 
condition (e.g., lichen sclerosus, 
endometriosis, pelvic inflammatory disease, genitourinary syndrome of menopause). In some 
cases, treating the medical 
condition may alleviate the genito-pelvic pain/penetration disorder. 
Much of the time, this is not 
the case. There are no reliable tools or diagnostic methods to allow 
clinicians to know whether the medical 
condition or genito-pelvic pain/penetration disorder is 



primary. Often, the associated medical 
conditions are difficult 
to diagnose and treat. For 
example, the increased incidence of postmenopausal 
pain during intercourse may sometimes be 
attributable to vaginal 
dryness or irritation associated with declining estrogen levels. The 
relationship, however, between genital symptoms, estrogen, and pain is not well understood. 


498 


Somatic 
symptom and 
related 
disorders. 
Some females with genito-pelvic pain/penetration disorder 
may also be diagnosable with somatic symptom 
disorder. Since both genito-pelvic 
pain/penetration disorder and the somatic symptom 
and related disorders are new diagnoses in 
DSM-5, it 
is not 
yet 
clear whether they can be reliably differentiated. Some females diagnosed 
with genito-pelvic pain/penetration disorder will also be diagnosed with a specific phobia. 


Inadequate 
sexual 
stimuli. 
It 
is important 
that 
the clinician, in considering differential 
diagnoses, 
assess the adequacy of sexual 
stimuli 
within the female s sexual 
experience. Sexual 
situations in 
which there is inadequate foreplay or arousal 
may lead to difficulties in penetration, pain, or 
avoidance. Erectile dysfunction or premature (early) ejaculation in the male partner may result 
in 
difficulties with penetration. These conditions should be carefully assessed. In some situations, a 
diagnosis of genito-pelvic pain/penetration disorder may not be appropriate. 


Comorbidity 


Comorbidity between genito-pelvic pain/penetration disorder and other sexual 
difficulties 
appears to be common. Comorbidity with relationship distress is also common and typically 
related to the lack of sexual 
intimacy rather than (solely) the pain itself. This is not 
surprising, 
because the inability to have (pain-free) intercourse with a desired partner and the avoidance of 
sexual 
opportunities may be either a contributing factor to or the result 
of other sexual 
or 
relationship problems. Because pelvic floor symptoms are implicated in the diagnosis of genitopelvic 
pain/penetration disorder, there is likely to be a higher prevalence of other disorders 
related to the pelvic floor or reproductive organs (e.g., interstitial 
cystitis, constipation, vaginal 
infection, endometriosis, irritable bowel 
syndrome). Females with genito-pelvic pain/penetration 
disorder frequently experience comorbid chronic pain conditions (e.g., fibromyalgia, chronic 
headaches), and the prevalence of these comorbidities increases with the severity of vulvar pain 
symptoms. 


Lesbian women also report 
genito-pelvic pain and penetration difficulties during sexual 
activities; 
the frequency of genito-pelvic pain/penetration symptoms among nonheterosexual 
women has been shown to be less than or the same as among heterosexual women. 


Male Hypoactive Sexual 
Desire Disorder 


Diagnostic Criteria 
F52.0 


A. 
Persistently or recurrently deficient 
(or absent) sexual/erotic thoughts or 
fantasies and 
desire 
for sexual activity. 
The 
judgment 
of 
deficiency is made 
by 

the 
clinician, 
taking 
into 
account 
factors that 
affect 
sexual functioning, 
such 
as 
age 
and 
general and 
sociocultural contexts of 
the 
individual s life. 


B. 
The 
symptoms in 
Criterion 
A 
have 
persisted 
for a 
minimum duration 
of 
approximately 6 
months. 
C. 
The 
symptoms in 
Criterion 
A 
cause 
clinically significant 
distress in 
the 
individual. 
D. 
The 
sexual dysfunction 
is not 
better explained 
by a 
nonsexual mental disorder or 
as a 
consequence 
of 
severe 
relationship 
distress or other significant 
stressors 
and 
is not 
attributable 
to 
the 
effects of 
a 
substance/medication 
or another 
medical condition. 
Specify 
whether: 


Lifelong: 
The 
disturbance 
has been 
present 
since 
the 
individual became 
sexually active. 
Acquired: 
The 
disturbance 
began 
after a 
period 
of 
relatively normal sexual 


function. 


499 


Specify 
whether: 
Generalized: 
Not 
limited 
to 
certain 
types of 
stimulation, 
situations, 
or partners. 
Situational: 
Only occurs with 
certain 
types of 
stimulation, 
situations, 
or partners. 


Specify 
current 
severity: 
Mild: 
Evidence 
of 
mild 
distress over the 
symptoms in 
Criterion 
A. 
Moderate: 
Evidence 
of 
moderate 
distress over the 
symptoms in 
Criterion 
A. 
Severe: 
Evidence 
of 
severe 
or extreme 
distress over the 
symptoms in 
Criterion 


A. 


Diagnostic Features 


When an assessment 
for male hypoactive sexual 
desire disorder is being made, interpersonal 
context 
must 
be taken into account. A  desire discrepancy,  in which a man has lower desire for 
sexual 
activity than his partner, is not 
sufficient 
to diagnose male hypoactive sexual 
desire 
disorder. Both low/absent 
desire for sex and deficient/absent 
sexual 
thoughts or fantasies 
(Criterion A) are required for a diagnosis of the disorder. There may be variation across men in 
how sexual desire is expressed. 


The lack of desire for sex and deficient/absent 
erotic thoughts or fantasies must 
be persistent 
or recurrent and must occur for a minimum duration of approximately 6 months. The inclusion of 
this duration criterion is meant to safeguard against making a diagnosis in cases in which a man s 
low sexual 
desire may represent 
a reactive but 
temporary response to adverse life conditions. For 
example, the man s low sexual 
desire may be related to an acute stressor or loss of self-esteem 
(e.g., being fired from 
a job or experiencing financial 
difficulty such as business failure). If these 
stressors persist 
beyond 6 months along with low sexual 
desire, then clinician judgment 
determines the appropriateness of the male hypoactive sexual desire disorder diagnosis. 



Associated Features 


Male hypoactive sexual 
desire disorder is sometimes associated with erectile and/or ejaculatory 
concerns. For example, persistent 
difficulties obtaining an erection may lead a man to lose 
interest 
in sexual 
activity. Men with hypoactive sexual 
desire disorder often report 
that 
they no 
longer initiate sexual 
activity and that 
they are minimally receptive to a partner s attempt 
to 
initiate. Sexual 
activities (e.g., masturbation or partnered sexual 
activity) may sometimes occur 
even in the presence of low sexual 
desire. Relationship-specific preferences regarding patterns of 
sexual 
initiation must 
be taken into account 
when making a diagnosis of male hypoactive sexual 
desire disorder. Although men are more likely to initiate sexual 
activity, and thus low desire may 
be characterized by a pattern of noninitiation, many men may prefer to have their partner initiate 
sexual 
activity. In such situations, the man s lack of receptivity to a partner s initiation should be 
considered when evaluating low desire. 


In addition to the subtypes  lifelong/acquired  and  generalized/situational,  the following 
five factors must 
be considered during assessment 
and diagnosis of male hypoactive sexual 
desire disorder given that 
they may be relevant 
to etiology and/or treatment: 
1) partner factors 
(e.g., partner s sexual 
problems, partner s health status); 
2) relationship factors (e.g., poor 
communication, discrepancies in desire for sexual 
activity); 
3) individual 
vulnerability factors 
(e.g., poor body image, history of sexual 
or emotional 
abuse), psychiatric comorbidity (e.g., 
depression, anxiety), or stressors (e.g., job loss, bereavement); 
4) cultural/religious factors (e.g., 
inhibitions related to prohibitions against 
sexual 
activity; 
attitudes toward sexuality); 
and 5) 
medical 
factors relevant 
to prognosis, course, or treatment. Each of these factors may contribute 
differently to the presenting symptoms of different men with this disorder. 


Prevalence 


The prevalence of male hypoactive sexual 
desire disorder varies depending on country of origin 
and method of assessment. Estimates of prevalence in representative samples range 


500 


from 
3% to 17%. Sexual 
desire problems are less common in younger men (ages 16 24), with 
prevalence rates between 3% and 14%, compared with older men (ages 60 74 years), with 
prevalence rates between 16% and 28%. However, a persistent 
lack of interest 
in sex, lasting 6 
months or more, affects a smaller proportion of men (6%). Moreover, less than 2% of men report 
clinically significant 
distress associated with low desire. Studies on help-seeking behavior 
indicate that only 10.5% of men with sexual problems in the previous year sought help. 


Development and Course 


By definition, lifelong male hypoactive sexual 
desire disorder indicates that 
low or no sexual 
desire has always been present, whereas the acquired subtype would be assigned if the man s low 
desire developed after a period of normal 
sexual 
desire. There is a requirement 
that 
low desire 
persist 
for approximately 6 months or more; 
thus, short-term 
changes in sexual 
desire should not 
be diagnosed as male hypoactive sexual desire disorder. 


There is a normative age-related decline in sexual 
desire. The prevalence of low sexual 
desire 
in men increases with age, from 
approximately 5.2% prevalence at 
age 27 years to 18.5% at 
age 



50 years. Like women, men identify a variety of triggers for their sexual 
desire, and they 
describe a wide range of reasons that 
they choose to engage in sexual 
activity. Although erotic 
visual 
cues may be more potent 
elicitors of desire in younger men, the potency of sexual 
cues 
may decrease with age and must 
be considered when evaluating men for hypoactive sexual 
desire disorder. 


Risk and Prognostic Factors 


Temperamental. 
Mood and anxiety symptoms appear to be strong predictors of low desire in men. 
Up to half of men with a past 
history of psychiatric symptoms may have moderate or severe loss 
of desire, compared with only 15% of those without 
such a history. A man s feelings about 
himself, his perception of his partner s sexual 
desire toward him, feelings of being emotionally 
connected, and contextual 
variables may all 
negatively (as well 
as positively) affect 
sexual 
desire. 


Beliefs about 
sexuality (particularly restrictive sexual 
attitudes and conservative beliefs) are 
commonly associated with low sexual 
desire in men. Moreover, lack of erotic thoughts and 
concerns about 
erection during sexual 
activity are significant 
predictors of low sexual 
desire, as 
well as low confidence levels in erectile function. 


Environmental. 
Alcohol 
use may increase the occurrence of low desire. Other environmental 
determinants of low sexual 
desire include problematic dyadic relationships, reduced attraction 
toward the partner, living in a long-term 
relationship, sexual 
boredom, and professional 
stress. At 
the larger societal level, cohort studies in a few high-income countries indicate a trend toward the 
decrease of sexual desire in men in recent decades. 


Genetic 
and 
physiological. 
Endocrine disorders such as hyperprolactinemia and hypogonadism 
significantly affect 
sexual 
desire in men. Age is a significant 
risk factor for low desire in men. It 
is unclear whether or not 
men with low desire also have abnormally low levels of testosterone; 
however, among hypogonadal 
men, low desire is common. There also may be a critical 
threshold 
below which testosterone will 
affect 
sexual 
desire in men and above which there is little effect 
of 
testosterone on men s desire. 


Culture-Related Diagnostic Issues 


There is marked variability in prevalence rates of low desire across world regions, ranging from 
12.5% in Northern European men to 28% in Southeast 
Asian men ages 40 80 years. Distress 
about 
lack of sexual 
desire was significantly associated with sociocultural 
contexts (e.g., 
occupational 
stress) in a web-based survey across three European countries (Portugal, Croatia, 
and Norway). 


501 


Sex- and Gender-Related Diagnostic Issues 


In contrast 
to the classification of sexual 
dysfunctions in women, desire and arousal 
disorders 
have been retained as separate constructs in men. Despite some similarities in the experience of 
desire across men and women, and the fact 
that 
desire fluctuates over time and is dependent 
on 
contextual 
factors, men do report 
a significantly higher intensity and frequency of sexual 
desire 



compared with women. However, preliminary data suggest 
that 
the overlap between sexual 
desire and sexual 
arousal 
(erectile function) is also very common in men, particularly when they 
present 
for help regarding sexual 
problems. Regarding sexual 
orientation, data suggest 
that 
low 
sexual desire is more commonly reported by gay men (19%) than by heterosexual men (9%). 


Differential 
Diagnosis 


Nonsexual 
mental 
disorders. 
Nonsexual 
mental 
disorders, such as major depressive disorder, 
which is characterized by  markedly diminished interest 
or pleasure in all, or almost 
all, 
activities,  may explain the lack of sexual 
desire. If the lack of desire is better explained by 
another mental 
disorder, then a diagnosis of male hypoactive sexual 
desire disorder would not 
be 
made. 


Substance/medication 
use. 
An onset 
of male hypoactive sexual 
desire that 
coincides with the 
beginning of substance/medication use and that 
dissipates with discontinuation of the 
substance/medication or dose reduction is suggestive of a substance/medication-induced sexual 
dysfunction, which should be diagnosed instead of male hypoactive sexual desire disorder. 


Another medical 
condition. 
If the low/absent 
desire and deficient/absent 
erotic thoughts or 
fantasies are better explained by the effects of another medical 
condition (e.g., hypogonadism, 
diabetes mellitus, thyroid dysfunction, central 
nervous system 
disease), then a diagnosis of male 
hypoactive sexual desire disorder would not be made. 


Interpersonal 
factors. 
If interpersonal 
or significant 
contextual 
factors, such as severe relationship 
distress or other significant 
stressors, are associated with the loss of desire in the man, then a 
diagnosis of male hypoactive sexual desire disorder would not be made. 


Other sexual 
dysfunctions. 
The presence of another sexual 
dysfunction does not 
rule out 
a 
diagnosis of male hypoactive sexual 
desire disorder; 
there is some evidence that 
up to one-half of 
men with low sexual 
desire also have erectile difficulties, and slightly fewer may also have early 
ejaculation difficulties. If the man s low desire is explained by self-identification as an asexual, 
then a diagnosis of male hypoactive sexual desire disorder is not made. 


Comorbidity 


Male hypoactive sexual 
desire disorder is rarely the sole sexual 
diagnosis in men. Erectile 
dysfunction, delayed ejaculation, and premature (early) ejaculation are often comorbid 
diagnoses. Depression and other mental 
disorders, as well 
as endocrinological 
factors, are often 
comorbid with male hypoactive sexual desire disorder. 


Premature (Early) Ejaculation 


Diagnostic Criteria 
F52.4 


A. 
A 
persistent 
or recurrent 
pattern 
of 
ejaculation 
occurring 
during 
partnered 
sexual 
activity within 
approximately 1 
minute 
following 
vaginal penetration 
and 
before 
the 
individual wishes it. 

502 


Note: 
Although 
the 
diagnosis of 
premature 
(early) ejaculation 
may be 
applied 
to 
individuals engaged 
in 
nonvaginal sexual activities, 
specific duration 
criteria 
have 
not 
been 
established 
for these 
activities. 


B. 
The 
symptom in 
Criterion 
A 
must 
have 
been 
present 
for at 
least 
6 
months and 
must 
be 
experienced 
on 
almost 
all or all (approximately 75% 100%) occasions 
of 
sexual activity (in 
identified 
situational contexts or, 
if 
generalized, 
in 
all 
contexts). 
C. 
The 
symptom in 
Criterion 
A 
causes clinically significant 
distress in 
the 
individual. 
D. 
The 
sexual dysfunction 
is not 
better explained 
by a 
nonsexual mental disorder or 
as a 
consequence 
of 
severe 
relationship 
distress or other significant 
stressors 
and 
is not 
attributable 
to 
the 
effects of 
a 
substance/medication 
or another 
medical condition. 
Specify 
whether: 


Lifelong: 
The 
disturbance 
has been 
present 
since 
the 
individual became 
sexually active. 
Acquired: 
The 
disturbance 
began 
after a 
period 
of 
relatively normal sexual 


function. 


Specify 
whether: 
Generalized: 
Not 
limited 
to 
certain 
types of 
stimulation, 
situations, 
or partners. 
Situational: 
Only occurs with 
certain 
types of 
stimulation, 
situations, 
or partners. 


Specify 
current 
severity: 


Mild: 
Ejaculation 
occurring 
within 
approximately 30 
seconds to 
1 
minute 
of 
vaginal penetration. 
Moderate: 
Ejaculation 
occurring 
within 
approximately 15 30 
seconds of 
vaginal 


penetration. 
Severe: 
Ejaculation 
occurring 
prior to 
sexual activity, 
at 
the 
start 
of 
sexual 
activity, 
or within 
approximately 15 
seconds of 
vaginal penetration. 


Diagnostic Features 


Premature (early) ejaculation is manifested by ejaculation that 
occurs prior to or shortly after 
vaginal 
penetration, operationalized by an individual s estimate of ejaculatory latency (i.e., 
elapsed time before ejaculation) after vaginal 
penetration. Although the diagnostic criteria 
specify penile-vaginal 
sex, it 
is reasonable to assume that 
similar estimates of ejaculatory latency 
apply to males having sex with males, as well 
as to other sexual 
behaviors. Estimated and 
measured intravaginal 
ejaculatory latencies are highly correlated as long as the ejaculatory 
latency is of short 
duration; 
therefore, self-reported estimates of ejaculatory latency are sufficient 
for diagnostic purposes. A 60-second intravaginal 
ejaculatory latency time was previously 
considered to be an appropriate cutoff for the diagnosis of lifelong premature (early) ejaculation 
in men; 
however, expert 
consensus now considers this latency time to be too brief and instead 



recommends a 120-second threshold. 


Associated Features 


Many males with premature (early) ejaculation complain of a sense of lack of control 
over 
ejaculation and report 
apprehension about 
their anticipated inability to delay ejaculation on 
future sexual encounters. 


The following factors may be relevant 
in the evaluation of any sexual 
dysfunction: 
1) partner 
factors (e.g., partner s sexual 
problems, partner s health status); 
2) relationship factors (e.g., poor 
communication, discrepancies in desire for sexual 
activity); 
3) individual 
vulnerability factors 
(e.g., history of sexual 
or emotional 
abuse), psychiatric comorbidity (e.g., depression, anxiety), 
and stressors (e.g., job loss, bereavement); 
4) cultural/religious factors (e.g., lack of privacy, 
inhibitions related to prohibitions against 
sexual 
activity; 
attitudes toward sexuality); 
and 5) 
medical factors relevant to prognosis, course, or treatment. 


503 


Prevalence 


Estimates of the prevalence of premature (early) ejaculation vary widely depending on the 
definition utilized. Internationally, a prevalence range of 8% 30% has been reported across all 
ages, with even lower and higher rates in other studies. Prevalence of premature (early) 
ejaculation may increase with age. For example, the prevalence among males ages 18 30 in 
Switzerland and Turkey is about 
9% 11%, while the reported prevalence of concern among 
males ages 50 59 in the United States about 
how rapidly they ejaculate may be as high as 55%. 
When premature (early) ejaculation is defined as ejaculation occurring within approximately 1 
minute of vaginal penetration, only 1% 3% of males would be diagnosed with the disorder. 


Development and Course 


By definition, lifelong premature (early) ejaculation starts during a male s initial 
sexual 
experiences and persists thereafter. Some males may experience premature (early) ejaculation 
during their initial 
sexual 
encounters but 
gain ejaculatory control 
over time. It 
is the persistence 
of ejaculatory problems for longer than 6 months that 
determines the diagnosis of premature 
(early) ejaculation. In contrast, some males develop the disorder after a period of having a 
normal 
ejaculatory latency, known as acquired premature (early) ejaculation. 
There is far less 
known about 
acquired premature (early) ejaculation than about 
lifelong premature (early) 
ejaculation. The acquired form 
likely has a later onset, usually appearing during or after the 
fourth decade of life. Lifelong is relatively stable throughout life. 


Risk and Prognostic Factors 


Temperamental. 
Premature (early) ejaculation may be more common in males with anxiety 


disorders, especially social anxiety disorder. 
Genetic 
and 
physiological. 
There is a moderate genetic contribution to lifelong premature (early) 
ejaculation. Premature (early) ejaculation may be associated with dopamine transporter gene 
polymorphism 
or serotonin transporter gene polymorphism. Thyroid disease, prostatitis, and 



drug withdrawal 
are associated with acquired premature (early) ejaculation. Positron emission 
tomography measures of regional 
cerebral 
blood flow during ejaculation have shown primary 
activation in the mesocephalic transition zone, including the ventral tegmental area. 


Culture-Related Diagnostic Issues 


Perception of what 
constitutes a normal 
ejaculatory latency differs cross-culturally and may be 
related to varying awareness of sexual 
dysfunction, concern about 
sexual 
failure, and perceptions 
about 
the importance of sex. Measured ejaculatory latencies may differ in some countries. 
Cultural 
or religious factors may contribute to these differences. For example, reports of 
premature (early) ejaculation were more common in arranged marriages, because of factors such 
as anxiety over family pressures and lack of premarital sexual experience. 


Sex- and Gender-Related Diagnostic Issues 


Premature (early) ejaculation is a sexual 
dysfunction in men. Men and their sexual 
partners may 
differ in their perception of what 
constitutes an acceptable ejaculatory latency. There may be 
increasing concerns in women about 
early ejaculation in their sexual 
partners, which may be a 
reflection of changing societal attitudes concerning women s sexual activity. 


504 


Diagnostic Markers 


Ejaculatory latency is usually monitored in research settings by the sexual 
partner utilizing a 
timing device (e.g., stopwatch), though this is not 
ideal 
in real-life sexual 
situations. In clinical 
settings, the man s estimate of the time between intravaginal 
penetration and ejaculation should 
be accepted in lieu of stopwatch measurements. 


Association With Suicidal 
Thoughts or Behavior 


Among males receiving treatment 
for premature (early) ejaculation with comorbid depression, 
elevated rates of suicidal 
thoughts or behavior have been observed; 
although the affected males 
attributed the suicidal 
symptoms to their premature (early) ejaculation, the presence of 
depression was also a likely contributing factor. 


Functional 
Consequences of Premature (Early) Ejaculation 


A pattern of premature (early) ejaculation may be associated with decreased self-esteem 
and self-
confidence, a sense of lack of control, and adverse consequences for partner relationships. It 
may 
also cause personal 
distress and decreased sexual 
satisfaction in the sexual 
partner. Single males 
are more bothered than partnered males by premature (early) ejaculation because of its 
interference with seeking and maintaining new relationships. Ejaculation prior to penetration 
may be associated with difficulties in conception. 


Differential 
Diagnosis 


Substance/medication-induced 
sexual 
dysfunction. 
When problems with premature (early) 
ejaculation are attributable exclusively to substance use, intoxication, or withdrawal, 



substance/medication-induced sexual dysfunction should be diagnosed. 


Ejaculatory 
concerns 
that 
do 
not 
meet 
diagnostic 
criteria. 
It 
is necessary to identify males with normal 
ejaculatory latencies who desire longer ejaculatory latencies and males who have episodic 
premature (early) ejaculation (e.g., during the first 
sexual 
encounter with a new partner when a 
short 
ejaculatory latency may be common or normative). Neither of these situations would lead 
to a diagnosis of premature (early) ejaculation, even though these situations may be distressing to 
some males. 


Comorbidity 


Premature (early) ejaculation may be associated with erectile problems. In many cases, it 
may be 
difficult 
to determine which difficulty preceded the other. Lifelong premature (early) ejaculation 
may be associated with certain anxiety disorders. Acquired premature (early) ejaculation may be 
associated with prostatitis, thyroid disease, or drug withdrawal (e.g., during opioid withdrawal). 


Substance/Medication-Induced 
Sexual 
Dysfunction 


Diagnostic Criteria 


A. 
A 
clinically significant 
disturbance 
in 
sexual function 
is predominant 
in 
the 
clinical 
picture. 
B. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
of 
both 
(1) and 
(2): 
505 


1. 
The 
symptoms in 
Criterion 
A 
developed 
during 
or soon 
after substance 
intoxication 
or withdrawal or after exposure 
to 
or withdrawal from a 
medication. 
2. 
The 
involved 
substance/medication 
is capable 
of 
producing 
the 
symptoms in 
Criterion 
A. 
C. 
The 
disturbance 
is not 
better explained 
by a 
sexual dysfunction 
that 
is not 
substance/medication-induced. 
Such 
evidence 
of 
an 
independent 
sexual 
dysfunction 
could 
include 
the 
following: 
The 
symptoms precede 
the 
onset 
of 
the 
substance/medication 
use; 
the 
symptoms persist 
for a 
substantial period 
of 
time 
(e.g., 
about 
1 
month) after 
the 
cessation 
of 
acute 
withdrawal or severe 
intoxication; 
or there 
is other 
evidence 
suggesting 
the 
existence 
of 
an 
independent 
non-
substance/medication-induced 
sexual dysfunction 
(e.g., 
a 
history of 
recurrent 
non-substance/medication-related 
episodes). 


D. 
The 
disturbance 
does not 
occur exclusively during 
the 
course 
of 
a 
delirium. 
E. 
The 
disturbance 
causes clinically significant 
distress in 
the 
individual. 

Note: 
This diagnosis should 
be 
made 
instead 
of 
a 
diagnosis of 
substance 
intoxication 
or substance 
withdrawal only when 
the 
symptoms in 
Criterion 
A 
predominate 
in 
the 
clinical picture 
and 
are 
sufficiently severe 
to 
warrant 
clinical 
attention. 


Coding 
note: 
The 
ICD-10-CM codes for the 
[specific substance/medication]-induced 
sexual dysfunctions are 
indicated 
in 
the 
table 
below. 
Note 
that 
the 
ICD-10-CM code 
depends on 
whether or not 
there 
is a 
comorbid 
substance 
use 
disorder present 
for 
the 
same 
class of 
substance. 
In 
any case, 
an 
additional separate 
diagnosis of 
a 
substance 
use 
disorder is not 
given. 
If 
a 
mild 
substance 
use 
disorder is comorbid 
with 
the 
substance-induced 
sexual dysfunction, 
the 
4th 
position 
character is  1,  and 
the 
clinician 
should 
record 
 mild 
[substance] 
use 
disorder  before 
the 
substance-
induced 
sexual dysfunction 
(e.g., 
 mild 
cocaine 
use 
disorder with 
cocaine-induced 
sexual dysfunction ). 
If 
a 
moderate 
or severe 
substance 
use 
disorder is comorbid 
with 
the 
substance-induced 
sexual dysfunction, 
the 
4th 
position 
character is  2,  and 
the 
clinician 
should 
record 
 moderate 
[substance] 
use 
disorder  or  severe 
[substance] 
use 
disorder,  depending 
on 
the 
severity of 
the 
comorbid 
substance 
use 
disorder. 
If 
there 
is no 
comorbid 
substance 
use 
disorder (e.g., 
after a 
one-time 
heavy 
use 
of 
the 
substance), 
then 
the 
4th 
position 
character is  9,  and 
the 
clinician 
should 
record 
only the 
substance-induced 
sexual dysfunction. 


ICD-10-CM 


With 
mild 
use 
With 
moderate 
or 
Without 
use 
disorder 
severe 
use 
disorder 
disorder 
Alcohol 
F10.181 
F10.281 
F10.981 
Opioid 
F11.181 
F11.281 
F11.981 
Sedative, 
hypnotic, 
or 
anxiolytic 
F13.181 
F13.281 
F13.981 
Amphetamine-type 
substance 
(or 
other 
stimulant) 
F15.181 
F15.281 
F15.981 
Cocaine 
F14.181 
F14.281 
F14.981 
Other 
(or 
unknown) 
substance 
F19.181 
F19.281 
F19.981 


506 


Specify 
(see 
Table 
1 
in 
the 
chapter  Substance-Related 
and 
Addictive 
Disorders,  
which 
indicates whether  with 
onset 
during 
intoxication  and/or  with 
onset 
during 
withdrawal  applies to 
a 
given 
substance 
class; 
or specify 
 with 
onset 
after 
medication 
use ): 


With 
onset during 
intoxication: 
If 
criteria 
are 
met 
for intoxication 
with 
the 


substance 
and 
the 
symptoms develop 
during 
intoxication. 
With 
onset during 
withdrawal: 
If 
criteria 
are 
met 
for withdrawal from the 
substance 
and 
the 
symptoms develop 
during, 
or shortly after, 
withdrawal. 


With 
onset after medication 
use: 
If 
symptoms developed 
at 
initiation 
of 
medication, 
with 
a 
change 
in 
use 
of 
medication, 
or during 
withdrawal of 
medication. 



Specify 
current 
severity: 
Mild: 
Occurs on 
25% 50% of 
occasions of 
sexual activity. 
Moderate: 
Occurs on 
50% 75% of 
occasions of 
sexual activity. 
Severe: 
Occurs on 
75% or more 
of 
occasions of 
sexual activity. 


Recording Procedures 


The name of the substance/medication-induced sexual 
dysfunction begins with the specific 
substance (e.g., alcohol) that 
is presumed to be causing the sexual 
dysfunction. The ICD-10-CM 
code that 
corresponds to the applicable drug class is selected from 
the table included in the 
criteria set. For substances that 
do not 
fit 
into any of the classes (e.g., fluoxetine), the ICD-10CM 
code for the other (or unknown) substance class should be used and the name of the specific 
substance recorded (e.g., F19.981 fluoxetine-induced sexual 
dysfunction). In cases in which a 
substance is judged to be an etiological factor but the specific substance is unknown, the ICD-10CM 
code for the other (or unknown) substance class is used and the fact 
that 
the substance is 
unknown is recorded (e.g., F19.981 unknown substance-induced sexual dysfunction). 


When recording the name of the disorder, the comorbid substance use disorder (if any) is 
listed first, followed by the word  with,  followed by the name of the substance-induced sexual 
dysfunction, followed by the specification of onset 
(i.e., onset 
during intoxication, onset 
during 
withdrawal, with onset 
after medication use), followed by the severity specifier (e.g., mild, 
moderate, severe). For example, in the case of erectile dysfunction occurring during intoxication 
in a man with a severe alcohol 
use disorder, the diagnosis is F10.281 severe alcohol 
use disorder 
with alcohol-induced sexual 
dysfunction, with onset 
during intoxication, moderate. A separate 
diagnosis of the comorbid severe alcohol 
use disorder is not 
given. If the substance-induced 
sexual 
dysfunction occurs without 
a comorbid substance use disorder (e.g., after a one-time 
heavy use of the substance), no accompanying substance use disorder is noted (e.g., F15.981 
amphetamine-induced sexual 
dysfunction, with onset 
during intoxication). When more than one 
substance is judged to play a significant 
role in the development 
of the sexual 
dysfunction, each 
should be listed separately (e.g., F14.181 mild cocaine use disorder with cocaine-induced sexual 
dysfunction, with onset 
during intoxication, moderate; 
F19.981 fluoxetine-induced sexual 
dysfunction, with onset after medication use, moderate). 


Diagnostic Features 


The essential 
features of substance/medication-induced sexual 
dysfunction are clinically 
significant 
disturbances in sexual 
function that 
are predominant 
in the clinical 
picture (Criterion 


A) that 
are judged to be due to the effects of a substance (e.g., a drug of abuse or medication). 
The sexual 
dysfunction must 
have developed during or soon after substance intoxication or 
withdrawal 
or after exposure to or withdrawal 
from 
a medication, and the substances or 
medications must 
be capable of producing the symptoms (Criterion B2). Substance/medicationinduced 
sexual dysfunction due to a prescribed treatment for a 
507 


mental 
disorder or another medical 
condition must 
have its onset 
while the individual 
is 



receiving the medication (or during withdrawal, if a withdrawal 
is associated with the 
medication). Once the treatment 
is discontinued, the sexual 
dysfunction will 
usually improve or 
remit 
within days to several 
weeks (depending on the half-life of the substance/medication and 
the presence of withdrawal). The diagnosis of substance/medication-induced sexual 
dysfunction 
should not 
be given if the onset 
of the sexual 
dysfunction precedes the substance/medication 
intoxication or withdrawal, or if the symptoms persist 
for a substantial 
period of time (i.e., 
usually longer than 1 month) from the time of severe intoxication or withdrawal. 


Associated Features 


Sexual 
dysfunctions can occur in association with intoxication with the following classes of 
substances: 
alcohol; 
opioids; 
sedatives, hypnotics, or anxiolytics; 
stimulants (including cocaine); 
and other (or unknown) substances. Sexual 
dysfunctions can occur in association with 
withdrawal 
from 
the following classes of substances: 
alcohol; 
opioids; 
sedatives, hypnotics, or 
anxiolytics; 
and other (or unknown) substances. Medications that 
can induce sexual 
dysfunctions 
include antidepressants, antipsychotics, and hormonal contraceptives. 


The most 
commonly reported side effect 
of antidepressant 
drugs is difficulty with orgasm 
or 
ejaculation in men, and with arousal 
in women. Problems with desire and erection are less 
frequent. There is evidence that 
the effects of antidepressant 
medications on sexual 
dysfunction 
occur regardless of levels of depression. Approximately 30% of sexual 
complaints are clinically 
significant. Certain agents (i.e., bupropion, mirtazapine, nefazodone, and vilazodone) appear to 
have lower rates of sexual side effects than other antidepressants. 


The sexual 
problems associated with antipsychotic drugs, including problems with sexual 
desire, erection, lubrication, ejaculation, or orgasm, have occurred with typical 
as well 
as 
atypical 
agents. However, problems are less common with prolactin-sparing antipsychotics or 
those that do not block dopamine receptors. 


Although the effects of mood stabilizers on sexual 
function are unclear, it 
is possible that 
lithium 
and anticonvulsants, with the possible exception of lamotrigine, have adverse effects on 
sexual 
desire. Problems with orgasm 
may occur with gabapentin. Similarly, there may be a 
higher prevalence of erectile and orgasm 
problems associated with benzodiazepines. There have 
not been such reports with buspirone. 


Many nonpsychiatric medications, such as cardiovascular, cytotoxic, gastrointestinal, and 
hormonal 
agents, are associated with disturbances in sexual 
function. Use of 5-a-reductase 
inhibitors (e.g., dutasteride, finasteride) may reduce erectile function, ejaculatory function, and 
libido in men. 


Illicit 
substance use is associated with decreased sexual 
desire, erectile dysfunction, and 
difficulty reaching orgasm. Sexual 
dysfunctions are also seen in individuals receiving methadone 
but 
are seldom 
reported by individuals receiving buprenorphine. Chronic nicotine or chronic 
alcohol 
abuse are associated with erectile problems. Cannabis, like alcohol, is a central 
nervous 
system 
depressant, and its use may be a risk factor for sexual 
dysfunction; 
however, it 
has also 
been suggested to potentially improve satisfaction with orgasm. 


Prevalence 


The prevalence and the incidence of substance/medication-induced sexual 
dysfunction are 
unclear, likely because of underreporting of treatment-emergent 
sexual 
side effects. Data on 



substance/medication-induced sexual 
dysfunction typically concern the effects of antidepressant 
drugs. The prevalence of antidepressant-induced sexual 
dysfunction varies in part 
depending on 
the specific agent. Approximately 25% 80% of individuals taking monoamine oxidase 
inhibitors, tricyclic antidepressants, serotonergic antidepressants, and combined serotonergicadrenergic 
antidepressants report sexual side effects. There 


508 


are differences in the incidence of sexual 
side effects between some serotonergic and combined 
adrenergic-serotonergic antidepressants, with medications such as citalopram, fluoxetine, 
fluvoxamine, paroxetine, sertraline, and venlafaxine having the highest 
rates of sexual 
dysfunction. 


Approximately 50% of individuals taking antipsychotic medications will 
experience adverse 
sexual 
side effects, including problems with sexual 
desire, erection, lubrication, ejaculation, or 
orgasm. The incidence of these side effects among different antipsychotic agents is unclear. 


Exact 
prevalence and incidence of sexual 
dysfunctions among users of nonpsychiatric 
medications such as cardiovascular, cytotoxic, gastrointestinal, and hormonal 
agents are 
unknown. Elevated rates of sexual 
dysfunction have been reported high-dose opioid drugs for 
pain. There are increased rates of decreased sexual 
desire, erectile dysfunction, and difficulty 
reaching orgasm 
associated with illicit 
substance use. The prevalence of sexual 
problems appears 
related to chronic drug abuse and appears higher in individuals who abuse heroin (approximately 
60% 70%) than in individuals who abuse amphetamine-type substances or 3,4methylenedioxymethamphetamine 
(i.e., MDMA, ecstasy). Elevated rates of sexual 
dysfunction 
are also seen in individuals receiving methadone but 
are seldom 
reported by individuals 
receiving buprenorphine. Chronic alcohol 
abuse and chronic nicotine abuse are related to higher 
rates of erectile problems. 


Development and Course 


The onset 
of antidepressant-induced sexual 
dysfunction may be as early as 8 days after the agent 
is first 
taken. Approximately 30% of individuals with mild to moderate orgasm 
delay will 
experience spontaneous remission of the dysfunction within 6 months. In some cases, serotonin 
reuptake inhibitor induced sexual 
dysfunction may persist 
after the agent 
is discontinued. The 
time to onset 
of sexual 
dysfunction after initiation of antipsychotic drugs or drugs of abuse is 
unknown. It 
is probable that 
the adverse effects of nicotine and alcohol 
may not 
appear until 
after 
years of use. Premature (early) ejaculation can sometimes occur after cessation of opioid use. 
There is some evidence that 
disturbances in sexual 
function related to substance/medication use 
increase with age. 


Culture-Related Diagnostic Issues 


There may be an interaction among cultural 
factors, the influence of medications on sexual 
functioning, and the response of the individual to those changes. 


Sex- and Gender-Related Diagnostic Issues 


Some gender differences in sexual 
side effects from 
substances and medications may exist, such 



that 
men may more often report 
impairments with desire and orgasm 
following antidepressant 
use, and women may more often report difficulties with sexual arousal. 


Functional 
Consequences of Substance/Medication-Induced Sexual 
Dysfunction 


Medication-induced sexual 
dysfunction may result 
in medication noncompliance, such as 
stopping medications or using them 
irregularly, which could contribute to the lack of efficacy for 
antidepressants. 


Differential 
Diagnosis 


Non-substance/medication-induced 
sexual 
dysfunctions. 
Many mental 
disorders, such as depressive, 
bipolar, anxiety, and psychotic disorders, are associated with disturbances of sexual 
function. 
Thus, differentiating a substance/medication-induced sexual 


509 


dysfunction from 
a manifestation of the underlying mental 
disorder can be quite difficult. The 
diagnosis is usually established if a close relationship between substance/medication initiation or 
discontinuation is observed. A clear diagnosis can be established if the problem 
occurs after 
substance/medication initiation, dissipates with substance/medication discontinuation, and recurs 
with introduction of the same agent. Most 
substance/medication-induced side effects occur 
shortly after initiation or discontinuation. Sexual 
side effects that 
only occur after chronic use of 
a substance/medication may be extremely difficult to diagnose with certainty. 


Other Specified 
Sexual 
Dysfunction 


F52.8 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
sexual 
dysfunction 
that 
cause 
clinically significant 
distress in 
the 
individual predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
sexual dysfunctions 
diagnostic class. 
The 
other specified 
sexual dysfunction 
category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific sexual dysfunction. 
This is 
done 
by recording 
 other specified 
sexual dysfunction  followed 
by the 
specific 
reason 
(e.g., 
 sexual aversion ). 


Unspecified 
Sexual 
Dysfunction 


F52.9 
This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
sexual 



dysfunction 
that 
cause 
clinically significant 
distress in 
the 
individual predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
sexual dysfunctions 
diagnostic class. 
The 
unspecified 
sexual dysfunction 
category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for 
a 
specific sexual dysfunction, 
and 
includes presentations for which 
there 
is 
insufficient 
information 
to 
make 
a 
more 
specific diagnosis. 


510 



511 



Gender Dysphoria 


In this chapter, 
there is one overarching diagnosis of gender dysphoria, with separate 
developmentally appropriate criteria sets for children and for adolescents and adults. The area of 
sex and gender is highly controversial 
and has led to a proliferation of terms whose meanings 
vary over time and within and between disciplines. An additional 
source of confusion is that 
in 
English  sex  connotes both male/female and sexuality. This chapter employs constructs and 
terms as they are widely used by clinicians from 
various disciplines with specialization in 
treating gender dysphoria. In this chapter, sex 
and sexual 
refer to the biological 
indicators of 
male and female (understood in the context 
of reproductive capacity), such as in sex 
chromosomes, gonads, sex hormones, and nonambiguous internal 
and external 
genitalia. 
Disorders of sex development 
or differences of sex development 
(DSDs) included the historical 
terms hermaphroditism 
and pseudohermaphroditism. DSDs include somatic intersex conditions 
such as congenital 
development 
of ambiguous genitalia (e.g., clitoromegaly, micropenis), 
congenital disjunction of internal and external sex anatomy (e.g., complete androgen insensitivity 
syndrome), incomplete development 
of sex anatomy (e.g., gonadal 
agenesis), sex chromosome 
anomalies (e.g., Turner syndrome; 
Klinefelter syndrome), or disorders of gonadal 
development 
(e.g., ovotestes). 


Gender 
is used to denote the public, sociocultural 
(and usually legally recognized) lived role 
as boy or girl, man or woman, or other gender. Biological 
factors are seen as contributing, in 
interaction with social 
and psychological 
factors, to gender development. Gender assignment 
refers to the assignment 
as male or female. This occurs usually at 
birth based on phenotypic sex 
and, thereby, yields the birth-assigned gender, historically referred to as  biological 
sex  or, 
more recently,  natal 
gender.  Birth-assigned sex 
is often used interchangeably with birth-
assigned gender. The terms assigned sex 
and assigned gender 
encompass birth-assigned 
sex/gender but 
also include gender/sex assignments and reassignments made after birth but 
during infancy or early childhood, usually in the case of intersex conditions. Gender-atypical 
refers to somatic features or behaviors that 
are not 
typical 
(in a statistical 
sense) of individuals 
with the same assigned gender in a given society and historical 
era; 
gender-nonconforming, 
gender variant, and gender diverse 
are alternative nondiagnostic terms. Gender reassignment 
denotes an official 
(and sometimes legal) change of gender. Gender-affirming treatments 
are 
medical 
procedures (hormones or surgeries or both) that 
aim 
to align an individual s physical 
characteristics with their experienced gender. Gender identity 
is a category of social 
identity and 
refers to an individual s identification as male, female, some category in between (i.e., gender 
fluid), or a category other than male or female (i.e., gender neutral). There has been a 
proliferation of gender identities in recent 
years. Gender dysphoria 
as a general 
descriptive term 
refers to the distress that 
may accompany the incongruence between one s experienced or 
expressed gender and one s assigned gender. However, it 
is more specifically defined when used 
as a diagnostic category. It 
does not 
refer to distress related to stigma, a distinct 
although 



possibly co-occurring source of distress. Transgender 
refers to the broad spectrum 
of individuals 
whose gender identity is different 
from 
their birth-assigned gender. Cisgender 
describes 
individuals whose gender expression is congruent 
with their birth-assigned gender (also 
nontransgender). Transsexual, a historic term, denotes an individual who seeks, is undergoing, 


512 


or has undergone a social 
transition from 
male to female or female to male, which in many, 
but 
not 
all, cases also involves a somatic transition by gender-affirming hormone treatment 
and 
genital, breast, or other gender-affirming surgery (historically referred to as sex reassignment 
surgery). 


Although not 
all 
individuals will 
experience distress from 
incongruence, many are distressed 
if the desired physical 
interventions using hormones and/or surgery are not 
available. The current 
term 
is more descriptive than the previous DSM-IV term 
gender identity disorder 
and focuses on 
dysphoria as the clinical problem, not identity per se. 


Gender Dysphoria 


Diagnostic Criteria 


F64.2Gender DysphoriainChildren
A. 
A 
marked 
incongruence 
between 
one s experienced/expressed 
gender and 
assigned 
gender, 
of 
at 
least 
6 
months  duration, 
as manifested 
by at 
least 
six of 
the 
following 
(one 
of 
which 
must 
be 
Criterion 
A1): 
1. 
A 
strong 
desire 
to 
be 
of 
the 
other gender or an 
insistence 
that 
one 
is the 
other 
gender (or some 
alternative 
gender different 
from one s assigned 
gender). 
2. 
In 
boys (assigned 
gender), 
a 
strong 
preference 
for cross-dressing 
or 
simulating 
female 
attire; 
or in 
girls (assigned 
gender), 
a 
strong 
preference 
for 
wearing 
only typical masculine 
clothing 
and 
a 
strong 
resistance 
to 
the 
wearing 
of 
typical feminine 
clothing. 
3. 
A 
strong 
preference 
for cross-gender roles in 
make-believe 
play or fantasy 
play. 
4. 
A 
strong 
preference 
for the 
toys, 
games, 
or activities stereotypically used 
or 
engaged 
in 
by the 
other gender. 
5. 
A 
strong 
preference 
for playmates of 
the 
other gender. 
6. 
In 
boys (assigned 
gender), 
a 
strong 
rejection 
of 
typically masculine 
toys, 
games, 
and 
activities and 
a 
strong 
avoidance 
of 
rough-and-tumble 
play; 
or in 
girls (assigned 
gender), 
a 
strong 
rejection 
of 
typically feminine 
toys, 
games, 
and 
activities. 
7. 
A 
strong 
dislike 
of 
one s sexual anatomy. 
8. 
A 
strong 
desire 
for the 
primary and/or secondary sex characteristics that 

match 
one s experienced 
gender. 


B. 
The 
condition 
is associated 
with 
clinically significant 
distress or impairment 
in 
social, 
school, 
or other important 
areas of 
functioning. 
Specify 
if: 
With 
a 
disorder/difference 
of sex 
development 
(e.g., 
a 
congenital 
adrenogenital disorder such 
as E25.0 
congenital adrenal hyperplasia 
or E34.50 
androgen 
insensitivity syndrome). 


Coding 
note: 
Code 
the 
disorder/difference 
of 
sex development 
as well as 
gender dysphoria. 


F64.0Gender DysphoriainAdolescentsandAdults
A. 
A 
marked 
incongruence 
between 
one s experienced/expressed 
gender 
and 
assigned 
gender, 
of 
at 
least 
6 
months  duration, 
as manifested 
by at 
least 
two 
of 
the 
following: 
1. 
A 
marked 
incongruence 
between 
one s experienced/expressed 
gender and 
primary and/or secondary sex characteristics (or in 
young 
adolescents, 
the 
anticipated 
secondary sex characteristics). 
513 


2. 
A 
strong 
desire 
to 
be 
rid 
of 
one s primary and/or secondary sex 
characteristics because 
of 
a 
marked 
incongruence 
with 
one s 
experienced/expressed 
gender (or in 
young 
adolescents, 
a 
desire 
to 
prevent 
the 
development 
of 
the 
anticipated 
secondary sex characteristics). 
3. 
A 
strong 
desire 
for the 
primary and/or secondary sex characteristics of 
the 
other gender. 
4. 
A 
strong 
desire 
to 
be 
of 
the 
other gender (or some 
alternative 
gender different 
from one s assigned 
gender). 
5. 
A 
strong 
desire 
to 
be 
treated 
as the 
other gender (or some 
alternative 
gender 
different 
from one s assigned 
gender). 
6. 
A 
strong 
conviction 
that 
one 
has the 
typical feelings and 
reactions of 
the 
other 
gender (or some 
alternative 
gender different 
from one s assigned 
gender). 
B. 
The 
condition 
is associated 
with 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Specify 
if: 
With 
a 
disorder/difference 
of sex 
development 
(e.g., 
a 
congenital 
adrenogenital disorder such 
as E25.0 
congenital adrenal hyperplasia 
or E34.50 
androgen 
insensitivity syndrome). 


Coding 
note: 
Code 
the 
disorder/difference 
of 
sex development 
as well as 
gender dysphoria. 
Specify 
if: 



Posttransition: 
The 
individual has transitioned 
to 
full-time 
living 
in 
the 
experienced 
gender (with 
or without 
legalization 
of 
gender change) and 
has 
undergone 
(or is preparing 
to 
have) at 
least 
one 
gender-affirming 
medical 
procedure 
or treatment 
regimen namely, 
regular gender-affirming 
hormone 
treatment 
or gender reassignment 
surgery confirming 
the 
experienced 
gender 
(e.g., 
breast 
augmentation 
surgery and/or vulvovaginoplasty in 
an 
individual 
assigned 
male 
at 
birth; 
transmasculine 
chest 
surgery and/or phalloplasty or 
metoidioplasty in 
an 
individual assigned 
female 
at 
birth). 


Specifiers 


The specifier  with a disorder/difference of sex development  should be used in the context 
of 
individuals who have a specific and codable disorder/difference of sex development 
documented 
in their medical record. 


The  posttransition  specifier may be used in the context 
of continuing treatment 
procedures 
that serve to support the new gender assignment. 


Diagnostic Features 


Individuals with gender dysphoria have a marked incongruence between the gender to which 
they have been assigned (usually based on phenotypic sex at 
birth, referred to as birth-assigned 
gender) and their experienced/expressed gender. This discrepancy is the core component 
of the 
diagnosis. There must 
also be evidence of distress about 
this incongruence. Experienced gender 
may include alternative gender identities beyond binary stereotypes. Consequently, distress may 
involve not 
only the experience that 
the individual 
is a male or female gender other than the one 
assigned at 
birth but 
also an experience that 
the individual 
is an intermediate or alternative 
gender that differs from the individual s birth-assigned gender. 


Gender dysphoria manifests itself differently in different age groups. The following examples 
may be less prominent in children raised in surroundings with fewer gender stereotypes. 


Prepubertal 
individuals assigned female at 
birth with gender dysphoria may express a 
marked, persistent feeling or conviction that they are a boy, express aversion to the idea of 


514 


being a girl, or assert 
they will 
grow up to be a man. They often prefer boys  clothing and 
hairstyles, may be perceived by strangers as boys, and may ask to be called by a boy s name. 
Sometimes they display intense negative reactions to parental attempts to have them wear dresses 
or other feminine attire. Some may refuse to attend school 
or social 
events where such clothes 
are required. These children may demonstrate marked gender nonconformity in role-playing, 
dreams, gender-typed play and toy preferences, styles, mannerisms, fantasies, and peer 
preferences. Contact 
sports, rough-and-tumble play, traditional 
boyhood games, and boys as 
playmates are most 
often preferred. They show little interest 
in stereotypically feminine toys 
(e.g., dolls) or activities (e.g., feminine dress-up or role-play). Occasionally, they refuse to 
urinate in a sitting position. Some may express a desire to have a penis or claim 
to have a penis 
or that 
they will 
grow one when older. They may also state that 
they do not 
want 
to develop 



breasts or menstruate. 


Prepubertal 
individuals assigned male at 
birth with gender dysphoria may express a marked, 
persistent feeling or conviction that they are a girl or assert that they will grow up to be a woman. 
They may express aversion to the idea of being a boy. They often prefer dressing in girls  or 
women s clothes or may improvise clothing from 
available materials (e.g., using towels, aprons, 
and scarves for long hair or skirts). These children may demonstrate marked gender 
nonconformity in gender-typed play and toy preferences, styles, mannerisms, and peer 
preferences. They may role-play female figures (e.g., playing  mother ) and may be intensely 
interested in female fantasy figures. Traditional 
feminine activities, stereotypical 
games, and 
pastimes (e.g.,  playing house ; 
drawing feminine pictures; 
watching television or videos of 
favorite female characters) may be preferred. Stereotypical 
female-type dolls (e.g., Barbie) may 
be favorite toys, and girls are their preferred playmates. They avoid rough-and-tumble play and 
have little interest 
in stereotypically masculine toys (e.g., cars, trucks). They may state that 
they 
find their penis or testes disgusting, that 
they wish them 
removed, or that 
they have, or wish to 
have, a vagina. 


Increasingly, parents are presenting to specialized clinics after their child with gender 
dysphoria has already socially transitioned. 


As the onset 
of puberty for individuals assigned female at 
birth is somewhere between ages 9 
and 13, and between 11 and 14 for individuals assigned male at 
birth, their symptoms and 
concerns may arise in a developmental 
phase somewhere between childhood and adolescence. 
As secondary sex characteristics of younger adolescents are not 
yet 
fully developed, these 
individuals may not 
state dislike of them, but 
they may be markedly distressed by imminent 
physical changes. 


In adolescents and adults with gender dysphoria, the discrepancy between experienced 
gender and physical 
sex characteristics is often, but 
not 
always, accompanied by a desire to be 
rid of primary and/or secondary sex characteristics and/or a strong desire to acquire some 
primary and/or secondary sex characteristics of another gender. To varying degrees, older 
adolescents and adults with gender dysphoria may adopt 
the behavior, clothing, and mannerisms 
of their experienced gender. They feel 
uncomfortable being regarded by others, or functioning in 
society, as members of their assigned gender. Some adults and adolescents may have a strong 
desire to be of a different 
gender and treated as such, and they may have an inner certainty to feel 
and respond as their experienced gender without 
seeking medical 
treatment 
to alter body 
characteristics. They may find other ways to resolve the incongruence between 
experienced/expressed and assigned gender by partially living in the desired role or by adopting 
a gender role neither conventionally male nor conventionally female. 


Associated Features 


When visible signs of puberty develop, individuals assigned male at 
birth may shave their facial, 
body, and leg hair at 
the first 
signs of growth. They sometimes bind their genitals to make 
erections less visible. Individuals assigned female at birth may bind their breasts, 


515 


walk with a stoop, or use loose sweaters to make breasts less visible. Increasingly, adolescents 



request, or may obtain without 
medical 
prescription and supervision, drugs that 
suppress 
production of gonadal 
steroids (e.g., gonadotropin-releasing hormone [GnRH] agonists) or that 
block gonadal 
hormone actions (e.g., spironolactone). Clinically referred adolescents often want 
hormone treatment 
and many also wish for gender-affirming surgery. Adolescents living in an 
accepting environment 
may openly express the desire to be and be treated as their experienced 
gender and dress partly or completely as their experienced gender, have a hairstyle typical 
of 
their experienced gender, preferentially seek friendships with peers of another gender, and/or 
adopt 
a new first 
name consistent 
with their experienced gender. Older adolescents, when 
sexually active, often do not 
show or allow partners to touch their sexual 
organs. For adults with 
an aversion toward their genitals, sexual 
activity is constrained by the preference that 
their 
genitals not 
be seen or touched by their partners. Not 
infrequently, adults may seek hormone 
treatment 
(sometimes without 
medical 
prescription and supervision) and gender-affirming 
surgery. Others are satisfied with either hormone treatment 
or surgery alone, or without 
any 
gender-affirming medical treatment. 


In children, adolescents, and adults with gender dysphoria, an overrepresentation of autism 
spectrum 
traits has been observed. Also, individuals with autism 
spectrum 
disorder are more 
likely to exhibit gender diversity. 


Adolescents and adults with gender dysphoria before gender-affirming treatment 
and legal 
gender change are at 
increased risk for mental 
health problems including suicidal 
ideation, 
suicide attempts, and suicides. After gender reassignment, adjustment 
may vary, and suicide risk 
and mental health problems may persist. 


In prepubertal 
children, increasing age is associated with having more behavioral 
or 
emotional 
problems; 
this is related to the increasing nonacceptance of gender-nonconforming 
behavior by others. Children and adolescents who feel 
supported and accepted in their gender 
nonconformity may show less or even no psychological problems. 


Prevalence 


There are no large-scale population studies of gender dysphoria. Based on gender-affirming 
treatment seeking populations, the prevalence for gender dysphoria diagnosis across populations 
has been assessed to be less than 1/1,000 (i.e., < 0.1%) for both individuals assigned male at 
birth 
and individuals assigned female at 
birth. Because many adults with gender dysphoria do not 
seek 
care at 
specialty treatment 
programs, prevalence rates are likely underestimates. Prevalence 
estimates based on surveys of self-reporting general 
population samples in the United States and 
Europe suggest 
higher numbers, although varied methods of assessment 
make comparisons 
difficult 
across studies. Self-identification as transgender ranges from 
0.5% to 0.6%; 
experiencing oneself as having an incongruent 
gender identity ranges from 
0.6% to 1.1%; 
feeling 
that 
one is a person of a different 
sex ranges from 
2.1% to 2.6%; 
and the desire to undergo 
medical treatment ranges from 0.2% to 0.6%. 


Development and Course 


Because expression of gender dysphoria varies with age, there are separate criteria sets for 
children versus those for adolescents and adults. Criteria for children are defined in a more 
concrete, behavioral 
manner than those for adolescents and adults. Young children are less likely 
than older children, adolescents, and adults to express extreme and persistent 
anatomic 



dysphoria. In adolescents and adults, incongruence between experienced gender and assigned 
gender is a central 
feature of the diagnosis. Factors related to distress and impairment 
also vary 
with age. A very young child may show signs of distress (e.g., intense crying) only when parents 
tell 
the child that 
he or she is  really  not 
a member of another gender but 
only  desires  to be. 
Distress may not 
be manifest 
in social 
environments supportive of the child s gender 
nonconformity and may emerge only if there is 


516 


parental/social 
interference with the child s gender variance. In adolescents and adults, distress 
may manifest 
because of strong incongruence between experienced gender and birth-assigned 
gender. Such distress may, however, be mitigated by supportive environments and knowledge 
that 
biomedical 
treatments exist 
to reduce incongruence. Impairment 
(e.g., school 
refusal, 
development 
of depression, anxiety, peer and behavioral 
problems, and substance abuse) may be 
a correlate of gender dysphoria. 


Gender dysphoria 
without 
a 
disorder of 
sex 
development. 


For clinic-referred children studied in 
Canada and the Netherlands, onset 
of gender-nonconforming behaviors is usually between ages 2 
and 4 years. This corresponds to the developmental 
time period in which most 
children begin 
expressing gendered behaviors and interests. For some preschool-age children, both marked, 
persistent 
gender-atypical 
behaviors and the expressed desire to be another gender may be 
present, or labeling themselves as a member of another gender may occur. In other cases, the 
gender expression appears later, usually at 
entry into elementary school. Children may 
sometimes express discomfort 
with their sexual 
anatomy or will 
state the desire to have a sexual 
anatomy corresponding to their experienced gender ( anatomic dysphoria ). Expressions of 
anatomic dysphoria become more common as children with gender dysphoria approach and 
anticipate puberty. 


No general 
population studies exist 
of adolescent 
or adult 
outcomes of childhood gender 
variance. Some prepubescent 
children expressing a desire to be another gender will 
not 
seek 
gender-affirming somatic treatments when they reach puberty. They frequently report 
nonheterosexual 
orientations and frequently marked gender-nonconforming behavior, although 
not 
necessarily a transgender identity in adolescence/young adulthood. Some children with 
gender dysphoria in childhood that 
remits in adolescence may experience a recurrence in 
adulthood. 


In individuals assigned male at 
birth, studies from 
North America and the Netherlands found 
persistence ranged from 
2% to 39%. In individuals assigned female at 
birth, persistence ranged 
from 
12% to 50%. Persistence of gender dysphoria is modestly correlated with dimensional 
measures of severity ascertained at 
the time of a childhood baseline assessment. Early social 
transition may also be a factor in persistence of gender dysphoria in adolescence. 


Studies have shown a high incidence of sexual 
attraction to those of the individual s birth-
assigned gender, regardless of the trajectory of the prepubescent 
child s gender dysphoria. For 
individuals whose gender dysphoria continues into adolescence and beyond, most 
self-identify as 
heterosexual. In those who no longer have gender dysphoria by the time of adolescence, a 
majority self-identify as gay, lesbian, or bisexual. 


Two broad trajectories have been described for development 
of gender dysphoria in 
individuals who identify as either male or female. 



As opposed to gender-nonconforming children, individuals with prepubertal-onset 
gender 
dysphoria have symptoms that 
meet 
diagnostic criteria for gender dysphoria in childhood. The 
dysphoria can continue into adolescence and adulthood; 
alternatively, some individuals go 
through a period in which the gender dysphoria either desists or is denied. At 
such times, these 
individuals may self-identify as being gay or lesbian. Some may identify as heterosexual 
and 
cisgender. However, it 
is possible that 
some of these individuals may experience a recurrence of 
gender dysphoria later in life. 


Regardless of whether the individual s gender dysphoria persists or desists at 
a later date, 
either the onset 
of puberty or the realization that 
puberty will 
begin with development 
of 
secondary sex characteristics can prompt 
distressing feelings of gender incongruence that 
can 
exacerbate the individual s gender dysphoria. 


The early/prepubertal-onset 
group often present 
for clinical, gender-affirming care during 
childhood, during adolescence, or in young adulthood. This may reflect 
a more intense gender 
dysphoria compared with individuals with late/postpubertal-onset 
gender dysphoria, whose 
distress may be more variable and less intense. 


517 


Late-onset 
or pubertal/postpubertal-onset 
gender dysphoria 
occurs around puberty or even 
much later in life. Some of these individuals report 
having had a desire to be of another gender in 
childhood that 
was not 
expressed verbally to others or had gender-nonconforming behavior that 
did not 
meet 
full 
criteria for gender dysphoria in childhood. Others have no recollection of any 
signs of childhood gender dysphoria. Parents of individuals with gender dysphoria of 
pubertal/postpubertal-onset 
often report 
surprise, as they saw no signs of gender dysphoria 
during childhood. 
Gender dysphoria 
in 
association 
with 
a 
disorder of 
sex 
development. 


Individuals with DSDs who 
require early medical 
intervention or decisions about 
gender assignment 
come to clinical 
attention at 
an early age. Depending on the condition, they may have been gonadectomized 
(often because of risk of future malignancy) before puberty so that 
administration of exogenous 
hormones is part 
of routine care to induce puberty. Infertility is common whether due to the 
condition itself or to gonadectomy, and genital 
surgery may have been done in infancy or 
childhood with the intent 
of affirming the assigned gender to both the affected individual 
and 
caregivers. 


Affected individuals may exhibit 
gender-nonconforming behavior starting in early childhood 
in a manner that 
is predictable depending on the specific DSD syndrome and the gender 
assignment, and thresholds for supporting social 
and medical 
gender transition in minors have 
traditionally been much lower for those with compared to those without 
DSDs. As individuals 
with some DSD syndromes become aware of their condition and medical 
history, many 
experience uncertainty about 
their gender, as opposed to developing a firm 
conviction that 
they 
are of another gender. The proportion who develop gender dysphoria and progress to gender 
transition varies markedly depending on the particular syndrome and gender assignment. 


Risk and Prognostic Factors 


Temperamental. 
Gender-variant 
behavior among individuals with prepubertal-onset 
gender 



dysphoria can develop in early preschool 
age. Studies suggest 
that 
a greater intensity of gender 
nonconformity and an older age at 
presentation make persistence of gender dysphoria into 
adolescence and adulthood more likely. A predisposing factor under consideration, especially in 
individuals with postpubertal-onset 
gender dysphoria (adolescence, adulthood), includes history 
of transvestism 
that 
may develop into autogynephilia (i.e., sexual 
arousal 
associated with the 
thought or image of oneself as a woman). 


Environmental. 
Individuals assigned male at 
birth with gender dysphoria without 
a DSD (in both 
childhood and adolescence) more commonly have older brothers when compared with cisgender 
males. 


Genetic 
and 
physiological. 
For individuals with gender dysphoria without 
a DSD, some genetic 
contribution is suggested by evidence for (weak) familiality of gender dysphoria among nontwin 
siblings, increased concordance for gender dysphoria in monozygotic compared with dizygotic 
same-sex twins, and some degree of heritability of gender dysphoria. Research suggests that 
gender dysphoria has a polygenetic basis involving interactions of several 
genes and 
polymorphisms that 
may affect 
in utero sexual 
differentiation of the brain, contributing to gender 
dysphoria in individuals assigned male at birth. 


As to endocrine findings in individuals with gender dysphoria, no endogenous systemic 
abnormalities in sex-hormone levels have been found in 46,XY individuals, whereas there appear 
to be increased androgen levels (in the range found in hirsute women but 
far below normal 
male 
levels) in 46,XX individuals. Overall, current 
evidence is insufficient 
to label 
gender dysphoria 
without a DSD as a form of intersexuality limited to the central nervous system. 


In gender dysphoria associated with a DSD, the likelihood of later gender dysphoria is 
increased if prenatal 
production and utilization (via receptor sensitivity) of androgens are grossly 
variant relative to what is usually seen in individuals with the same assigned 


518 


gender. Examples include 46,XY individuals with a history of normal 
male prenatal 
hormone 
milieu but 
inborn nonhormonal 
genital 
defects (as in cloacal 
bladder exstrophy or penile 
agenesis) and who have been assigned to the female gender. The likelihood of gender dysphoria 
is further enhanced by additional, prolonged, highly gender-variant 
postnatal 
androgen exposure 
with somatic virilization as may occur in female-raised and noncastrated 46,XY individuals with 
5-alpha reductase-2 deficiency or 17-beta-hydroxysteroid dehydrogenase-3 deficiency or in 
female-raised 46,XX individuals with classical 
congenital 
adrenal 
hyperplasia with prolonged 
periods of nonadherence to glucocorticoid replacement 
therapy. However, the prenatal 
androgen 
milieu is more closely related to gendered behavior than to gender identity. Many individuals 
with DSDs and markedly gender-variant 
behavior do not 
develop gender dysphoria. Thus, 
gender-nonconforming behavior by itself should not 
be interpreted as an indicator of current 
or 
future gender dysphoria. There appears to be a higher rate of gender dysphoria and patient-
initiated gender change from 
assigned female to male than from 
assigned male to female in 
individuals prenatally exposed to a full complement of masculinizing hormonal influences. 


Culture-Related Diagnostic Issues 


Individuals with gender dysphoria have been reported across many countries and cultural 



contexts around the world. The equivalent 
of gender dysphoria has also been reported in 
individuals living in cultural 
contexts with institutionalized gender identity categories other than 
men/boys or women/girls that sanction gender nonconforming development. These include India, 
Sri 
Lanka, Myanmar, Oman, Samoa, Thailand, and Indigenous Peoples of North America. It 
is 
unclear however, in such cultural 
contexts, whether the diagnostic criteria for gender dysphoria 
would be met with these individuals. 


The prevalence of coexisting mental 
health problems differs among cultures; 
these 
differences may also be related to differences in attitudes toward gender nonconformity in 
children, adolescents, and adults. However, also in some non-Western cultures, anxiety has been 
found to be relatively common in individuals with gender dysphoria, even in cultures with 
accepting attitudes toward gender-variant behavior. 


Sex- and Gender-Related Diagnostic Issues 


Sex differences in rate of referrals to specialty clinics vary by age group. In children, sex ratios 
of individuals assigned male at 
birth to individuals assigned female at 
birth range from 
1.25:1 to 


4.3:1. Studies show increasing numbers of children and adolescents presenting to specialty 
clinics, presentation at 
younger ages, more frequent 
early social 
transition, and a shift 
to a greater 
number of individuals assigned female at 
birth in adolescents and young adults than individuals 
assigned male at 
birth. In adults, estimates generally suggest 
more individuals assigned male at 
birth seek gender-affirming treatment, with ratios ranging from 
1:1 to 6.1:1 in most 
studies in the 
United States and Europe. 
Association With Suicidal 
Thoughts or Behavior 


Rates of suicidality and suicide attempts for transgender individuals are reported to range from 
30% to 80%, with risk factors including past 
maltreatment, gender victimization, depression, 
substance abuse, and younger age. Transgender adolescents referred to gender clinics have 
substantially higher rates of suicidal 
thoughts and behaviors when compared with nonreferred 
adolescents. Prior to receiving gender-affirming treatment 
and legal 
gender reassignment, 
adolescents and adults with gender dysphoria are at 
increased risk for suicidal 
thoughts and 
suicide attempts. After gender-affirming treatment, adjustment 
varies, and while improvement 
in 
coexisting symptoms is often seen, some individuals continue to experience prominent 
anxiety 
and affective symptoms and remain at increased risk for suicide. 


519 


A study of 572 children referred for gender identity concerns in Canada and several 
comparison groups (siblings, other referred children, and nonreferred children) largely from 
other high-income countries found that 
gender-referred children were 8.6 times more likely to 
self-harm 
or attempt 
suicide than comparison children, even after adjustment 
for overall 
behavior 
and peer relationship problems, and particularly in the second half of childhood. Among 
adolescents, the highest 
rate of suicide attempt 
is among transgender young men, followed by 
those defining themselves as neither male nor female. 


Functional 
Consequences of Gender Dysphoria 



Gender nonconformity may appear at 
all 
ages after the first 
2 3 years of childhood and may 
interfere with daily activities. In older children, gender nonconformity may affect 
peer 
relationships and may lead to isolation from 
peer groups and to distress. Many children 
experience teasing and harassment 
or pressure to dress in attire associated with their birth-
assigned sex, especially when growing up in a nonsupportive and nonaccepting environment. 
Also in adolescents and adults, the distress resulting from 
gender incongruence often interferes 
with daily activities. Relationship difficulties, including sexual 
relationship problems, are 
common, and functioning at 
school 
or at 
work may be impaired. Gender dysphoria is associated 
with high levels of stigmatization, discrimination, and victimization, leading to negative self-
concept, increased rates of depression, suicidality, and other mental 
disorder co-occurrence, 
school 
dropout, and economic marginalization, including unemployment, with attendant 
social 
and mental 
health risks, especially in individuals who lack family or social 
support. In addition, 
these individuals  access to health services and mental 
health services may be impeded by 
structural 
barriers, such as institutional 
discomfort 
about, inexperience with, or hostility toward 
working with this patient population. 


Differential 
Diagnosis 


Nonconformity 
to 
gender roles. 
Gender dysphoria should be distinguished from 
simple 
nonconformity to stereotypical 
gender role behavior by the strong desire to be of another gender 
than the assigned one and by the extent 
and pervasiveness of gender-variant 
activities and 
interests. The diagnosis is not 
meant 
to merely describe nonconformity to stereotypical 
gender 
role behavior (e.g.,  tomboyism  in girls,  girly-boy  behavior in boys, occasional cross-dressing 
in adult 
men). Given the increased openness of gender-diverse expressions by individuals across 
the entire range of the transgender spectrum, it 
is important 
that 
the clinical 
diagnosis be limited 
to those individuals whose distress and impairment meet the specified criteria. 


Transvestic 
disorder. 
Transvestic disorder is diagnosed in heterosexual 
(or bisexual) adolescent 
and adult 
males (rarely in females) for whom 
women s clothing generates sexual 
excitement 
and 
causes distress and/or impairment 
without 
drawing their assigned gender into question. It 
is 
occasionally accompanied by gender dysphoria. An individual 
with transvestic disorder who also 
has clinically significant 
gender dysphoria can be given both diagnoses. In some cases of 
postpubertal-onset 
gender dysphoria in individuals assigned male at 
birth who are attracted to 
women, cross-dressing with sexual 
excitement 
is a precursor to the diagnosis of gender 
dysphoria. 


Body 
dysmorphic 
disorder. 
An individual 
with body dysmorphic disorder focuses on the alteration 
or removal 
of a specific body part 
because it 
is perceived as abnormally formed, not 
because it 
represents a repudiated assigned gender. When an individual s presentation meets criteria for 
both gender dysphoria and body dysmorphic disorder, both diagnoses can be given. Individuals 
wishing to have a healthy limb 
amputated (termed by some body integrity identity disorder) 
because it 
makes them 
feel 
more  complete  usually do not 
wish to change gender, but 
rather 
desire to live as an amputee or a disabled person. 


Autism spectrum disorder. 
In individuals with autism 
spectrum 
disorder, diagnosing gender 
dysphoria can be challenging. It can be difficult to differentiate potential co-occurring 


520 



gender dysphoria from 
an autistic preoccupation because of the concrete and rigid thinking 
around gender roles and/or poor understanding of social 
relationships characteristic of autism 
spectrum disorder. 


Schizophrenia 
and 
other psychotic 
disorders. 
In schizophrenia, there may rarely be delusions of 
belonging to some other gender. In the absence of psychotic symptoms, insistence by an 
individual 
with gender dysphoria that 
he or she is another gender is not 
considered a delusion. 
Schizophrenia (or other psychotic disorders) and gender dysphoria may co-occur. Gender-
themed delusions may occur in up to 20% of individuals with schizophrenia. They can usually be 
differentiated from 
gender dysphoria by their bizarre content 
and by waxing and waning with 
remissions and exacerbations of psychotic episodes. 


Other clinical 
presentations. 
Some individuals with an emasculinization desire who develop an 
alternative, nonmale/nonfemale gender identity do have a presentation that 
meets criteria for 
gender dysphoria. However, some males seek genital 
surgery for either aesthetic reasons or to 
remove psychological 
effects of androgens without 
changing male identity; 
in these cases, the 
criteria for gender dysphoria are not met. 


Comorbidity 


Clinically referred children with gender dysphoria show elevated levels of anxiety, disruptive, 
impulse-control, and depressive disorders. Autism 
spectrum disorder is more prevalent 
in 
clinically referred adolescents and adults with gender dysphoria than in the general 
population. 
Clinically referred adolescents and adults with gender dysphoria often have high rates of 
associated mental 
disorders, with anxiety and depressive disorders being the most 
common. 
Individuals who have experienced harassment 
and violence may also develop posttraumatic 
stress disorder. 


Other Specified 
Gender Dysphoria 


F64.8 


This category applies to presentations in which symptoms characteristic of gender 
dysphoria that 
cause clinically significant 
distress or impairment 
in social, occupational, or 
other important 
areas of functioning predominate but 
do not 
meet 
the full 
criteria for gender 
dysphoria. The other specified gender dysphoria category is used in situations in which the 
clinician chooses to communicate the specific reason that 
the presentation does not 
meet 
the 
criteria for gender dysphoria. This is done by recording  other 
specified gender dysphoria  
followed by the specific reason (e.g.,  brief gender dysphoria,  in which symptoms meet 
full 
criteria for gender dysphoria but the duration is less than the required 6 months). 


Unspecified 
Gender Dysphoria 


F64.9 



This category applies to 
presentations in 
which 
symptoms characteristic of 
gender 
dysphoria 
that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for gender dysphoria. 
The 
unspecified 
gender dysphoria 
category is 
used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for gender dysphoria, 
and 
includes presentations in 
which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis. 



521 



Disruptive, 
Impulse-Control, 
and Conduct 
Disorders 


Disruptive, 
impulse-control, 
and conduct 
disorders include conditions 
involving problems in the self-control 
of emotions and behaviors. While other disorders in DSM5 
may also involve problems in emotional 
and/or behavioral 
regulation, the disorders in this 
chapter are unique in that 
these problems are manifested in behaviors that 
violate the rights of 
others (e.g., aggression, destruction of property) and/or that 
bring the individual 
into significant 
conflict 
with societal 
norms or authority figures. The underlying causes of the problems in the 
self-control 
of emotions and behaviors can vary greatly across the disorders in this chapter and 
among individuals within a given diagnostic category. 


The chapter includes oppositional 
defiant 
disorder, intermittent 
explosive disorder, conduct 
disorder, antisocial 
personality disorder (which is described in the chapter  Personality 
Disorders ), pyromania, kleptomania, and other specified and unspecified disruptive, impulse-
control, and conduct disorders. Although all the disorders in the chapter involve problems in both 
emotional 
and behavioral 
regulation, the source of variation among the disorders is the relative 
emphasis on problems in the two types of self-control. For example, the criteria for conduct 
disorder focus largely on poorly controlled behaviors that 
violate the rights of others or that 
violate major societal 
norms. These behaviors may or may not 
result 
from 
poorly controlled 
emotions. Some symptoms of conduct 
disorder (e.g., certain forms of aggression) can be 
attributable to constricted emotional 
responses. At 
the other extreme, the criteria for intermittent 
explosive disorder focus largely on poorly controlled emotion, outbursts of anger that 
are 
disproportionate to the interpersonal or other provocation or to other psychosocial stressors. 


Intermediate in impact 
to these two disorders is oppositional 
defiant 
disorder, in which the 
criteria are more evenly distributed between emotions (anger and irritation) and behaviors 
(argumentativeness and defiance). Pyromania and kleptomania are characterized by poor impulse 
control 
related to specific behaviors (fire setting or stealing) that 
relieve internal 
tension. Other 
specified disruptive, impulse-control, and conduct 
disorder is a category for conditions in which 
there are symptoms of conduct 
disorder, oppositional 
defiant 
disorder, or other disruptive, 
impulse-control, and conduct 
disorders, but 
the number or type of symptoms does not 
meet 
the 
diagnostic threshold for any of the disorders in this chapter, even though there is evidence of 
clinically significant impairment associated with the symptoms. 


The disruptive, impulse-control, and conduct 
disorders all 
tend to be more common in boys 
and men than in girls and women, although the relative degree of male predominance may differ 
both across disorders and within a disorder at 
different 
ages. The disorders in this chapter tend to 
have first 
onset 
in childhood or adolescence. In fact, it 
is very rare for either conduct 
disorder or 
oppositional 
defiant 
disorder to first 
emerge in adulthood. There is a developmental 
relationship 
between oppositional 
defiant 
disorder and conduct 
disorder, in that 
most 
cases of conduct 



disorder previously would have had symptoms that 
met 
criteria for oppositional 
defiant 
disorder, 
at 
least 
in those cases in which conduct 
disorder emerges prior to adolescence. However, most 
children with oppositional 
defiant 
disorder do not 
eventually develop conduct 
disorder. 
Furthermore, children with 


522 


oppositional 
defiant 
disorder are at 
risk for eventually developing other problems besides 
conduct disorder, including anxiety and depressive disorders. 


Many of the symptoms that 
define the disruptive, impulse-control, and conduct 
disorders are 
behaviors that 
can occur to some degree in typically developing persons. Thus, it 
is critical 
that 
the frequency, persistence, pervasiveness across situations, and impairment 
associated with the 
behaviors indicative of the diagnosis be considered relative to what 
is normative for a person s 
age, gender, and culture when determining if they are symptomatic of a disorder. 


The disruptive, impulse-control, and conduct 
disorders have been linked to a common 
externalizing spectrum 
associated with the personality dimensions of disinhibition 
and negative 
emotionality 
(some facets); 
and inversely with constraint 
and agreeableness. These shared 
personality dimensions could account 
for the high level 
of comorbidity among these disorders 
and their frequent 
comorbidity with substance use disorders and antisocial 
personality disorder. 
However, the specific nature of the shared diathesis that 
constitutes the externalizing spectrum 
remains unknown. 


Oppositional 
Defiant Disorder 


Diagnostic Criteria 
F91.3 


A. 
A 
pattern 
of 
angry/irritable 
mood, 
argumentative/defiant 
behavior, 
or 
vindictiveness lasting 
at 
least 
6 
months as evidenced 
by at 
least 
four symptoms 
from any of 
the 
following 
categories, 
and 
exhibited 
during 
interaction 
with 
at 
least 
one 
individual who 
is not 
a 
sibling. 
Angry/Irritable 
Mood 


1. 
Often 
loses temper. 
2. 
Is often 
touchy or easily annoyed. 
3. 
Is often 
angry and 
resentful. 
Argumentative/Defiant Behavior 


4. 
Often 
argues with 
authority figures or, 
for children 
and 
adolescents, 
with 
adults. 
5. 
Often 
actively defies or refuses to 
comply with 
requests from authority figures 
or with 
rules. 
6. 
Often 
deliberately annoys others. 
7. 
Often 
blames others for his or her mistakes or misbehavior. 

Vindictiveness 


8. 
Has been 
spiteful or vindictive 
at 
least 
twice 
within 
the 
past 
6 
months. 
Note: 
The 
persistence 
and 
frequency of 
these 
behaviors should 
be 
used 
to 
distinguish 
a 
behavior that 
is within 
normal limits from a 
behavior that 
is 
symptomatic. 
For children 
younger than 
5 
years, 
the 
behavior should 
occur on 
most 
days for a 
period 
of 
at 
least 
6 
months unless otherwise 
noted 
(Criterion 
A8). 
For individuals 5 
years or older, 
the 
behavior should 
occur at 
least 
once 
per week for at 
least 
6 
months, 
unless otherwise 
noted 
(Criterion 
A8). 
While 
these 
frequency criteria 
provide 
guidance 
on 
a 
minimal level of 
frequency to 
define 
symptoms, 
other factors should 
also 
be 
considered, 
such 
as whether the 
frequency and 
intensity of 
the 
behaviors are 
outside 
a 
range 
that 
is normative 
for the 
individual s developmental level, 
gender, 
and 
culture. 


B. 
The 
disturbance 
in 
behavior is associated 
with 
distress in 
the 
individual or others 
in 
his or her immediate 
social context 
(e.g., 
family, 
peer group, 
work colleagues), 
or it 
impacts negatively on 
social, 
educational, 
occupational, 
or other important 
areas of 
functioning. 
523 


C. 
The 
behaviors do 
not 
occur exclusively during 
the 
course 
of 
a 
psychotic, 
substance 
use, 
depressive, 
or bipolar disorder. 
Also, 
the 
criteria 
are 
not 
met 
for 
disruptive 
mood 
dysregulation 
disorder. 
Specify 
current 
severity: 


Mild: 
Symptoms are 
confined 
to 
only one 
setting 
(e.g., 
at 
home, 
at 
school, 
at 
work, 
with 
peers). 
Moderate: 
Some 
symptoms are 
present 
in 
at 
least 
two 
settings. 
Severe: 
Some 
symptoms are 
present 
in 
three 
or more 
settings. 


Specifiers 


It 
is not 
uncommon for individuals with oppositional 
defiant 
disorder to show symptoms only at 
home and only with family members. However, the pervasiveness of the symptoms is an 
indicator of the severity of the disorder. 


Diagnostic Features 


The essential 
feature of oppositional 
defiant 
disorder is a frequent 
and persistent 
pattern of 
angry/irritable mood, argumentative/defiant 
behavior, or vindictiveness (Criterion A). It 
is not 
unusual 
for individuals with oppositional 
defiant 
disorder to show the behavioral 
features of the 
disorder without 
problems of negative mood. However, individuals with the disorder who show 
the angry/irritable mood symptoms typically show the behavioral features as well. 


The symptoms of oppositional 
defiant 
disorder may be confined to only one setting, and this 
is most 
frequently the home. Individuals who show enough symptoms to meet 
the diagnostic 
threshold, even if it 
is only at 
home, may be significantly impaired in their social 
functioning. 



However, in more severe cases, the symptoms of the disorder are present 
in multiple settings. 
Given that 
the pervasiveness of symptoms is an indicator of the severity of the disorder, it 
is 
critical 
that 
the individual s behavior be assessed across multiple settings and relationships. 
Because these behaviors are common among siblings, they must 
be observed during interactions 
with persons other than siblings. Also, because symptoms of the disorder are typically more 
evident 
in interactions with adults or peers whom 
the individual 
knows well, they may not 
be 
apparent during a clinical examination. 


The symptoms of oppositional 
defiant 
disorder can occur to some degree in persons without 
this disorder. There are several 
key considerations for determining if the behaviors are 
symptomatic of oppositional 
defiant 
disorder. First, the diagnostic threshold of four or more 
symptoms within the preceding 6 months must 
be met. Second, the persistence and frequency of 
the symptoms should exceed what 
is normative for an individual s age, gender, and culture. 
Temper outbursts for a preschool 
child would be considered a symptom 
of oppositional 
defiant 
disorder only if they occurred on most 
days for the preceding 6 months, if they occurred with at 
least 
three other symptoms of the disorder, and if the temper outbursts contributed to the 
significant 
impairment 
associated with the disorder (e.g., led to destruction of property during 
outbursts, resulted in the child being asked to leave a preschool). It 
should be noted that 
temper 
loss need not 
always involve tantrum 
behavior and can be displayed by angry facial 
expressions, 
verbal 
expressions of anger, and subjective feelings of anger that 
would not 
typically be 
considered a tantrum. 


The symptoms of the disorder often are part 
of a pattern of problematic interactions with 
others. Furthermore, individuals with this disorder typically do not 
regard themselves as angry, 
oppositional, or defiant. Instead, they often justify their behavior as a response to unreasonable 
demands or circumstances. Thus, it 
can be difficult 
to disentangle the relative contribution of the 
individual 
with the disorder to the problematic interactions he or she experiences. For example, 
children with oppositional defiant disorder may have 


524 


experienced a history of hostile parenting, and it 
is often impossible to determine if the 
child s behavior caused the parents to act 
in a more hostile manner toward the child, if the 
parents  hostility led to the child s problematic behavior, or if there was some combination of 
both. Whether or not 
the clinician can separate the relative contributions of potential 
causal 
factors should not 
influence whether the diagnosis is made. In the event 
that 
the child may be 
living in particularly poor conditions where neglect 
or mistreatment 
may occur (e.g., in 
institutional 
settings), clinical 
attention to reducing the contribution of the environment 
may be 
helpful. 


Associated Features 


Two of the most 
common co-occurring conditions with oppositional 
defiant 
disorder are 
attention-deficit/hyperactivity disorder (ADHD) and conduct 
disorder (see the section 
 Comorbidity  for this disorder). Oppositional 
defiant 
disorder has been associated with 
increased risk for suicide attempts, even after comorbid disorders are controlled for. 



Prevalence 


The cross-national 
prevalence of oppositional 
defiant 
disorder ranges from 
1% to 11%, with an 
average prevalence estimate of around 3.3%. The rate of oppositional 
defiant 
disorder may vary 
depending on the age and gender of the child. The disorder appears to be somewhat 
more 
prevalent 
in boys than in girls (1.59:1) prior to adolescence. This male predominance is not 
consistently found in samples of adolescents or adults. 


Development and Course 


The first 
symptoms of oppositional 
defiant 
disorder usually appear during the preschool 
years 
and rarely later than early adolescence. Oppositional 
defiant 
disorder often precedes the 
development 
of conduct 
disorder, especially for those with the childhood-onset 
type of conduct 
disorder. However, many children and adolescents with oppositional 
defiant 
disorder do not 
subsequently develop conduct 
disorder. Oppositional 
defiant 
disorder also conveys risk for the 
development 
of anxiety disorders and major depressive disorder, even in the absence of conduct 
disorder. The defiant, argumentative, and vindictive symptoms carry most 
of the risk for conduct 
disorder, whereas the angry/irritable mood symptoms carry most 
of the risk for mood and 
anxiety disorders. 


Manifestations of the disorder across development 
appear consistent. Children and 
adolescents with oppositional 
defiant 
disorder are at 
increased risk for a number of problems in 
adjustment 
as adults, including functional 
impairments (e.g., problems in relationships with 
family, peers, and romantic partners; 
lower educational 
attainment; 
more workplace stress), the 
persistence of oppositional 
defiant 
disorder, and other psychopathology, such as antisocial 
behavior, impulse-control problems, substance misuse, anxiety, and depression. 


Many of the behaviors associated with oppositional 
defiant 
disorder increase in frequency 
during the preschool 
period and in adolescence. Thus, it 
is especially critical 
during these 
development 
periods that 
the frequency and intensity of these behaviors be evaluated against 
normative levels before it 
is decided that 
they are symptoms of oppositional 
defiant 
disorder. For 
example, it 
is not 
unusual 
for preschool 
children to show temper tantrums on a weekly basis, but 
daily tantrums occur in only about 10% of preschool children. 


Risk and Prognostic Factors 


Temperamental. 
Temperamental 
factors related to problems in emotional 
regulation (e.g., high 
levels of emotional reactivity, poor frustration tolerance) have been predictive of the disorder. 


525 


Environmental. 
Children with oppositional 
defiant 
disorder influence their environments, which 
in turn can influence them. For example, harsh, inconsistent, or neglectful 
child-rearing practices 
predict 
increases in symptoms, and oppositional 
symptoms predict 
increases in harsh and 
inconsistent 
parenting. In children and adolescents, oppositional 
defiant 
disorder is more 
prevalent 
in families in which childcare is disrupted by a succession of different 
caregivers. 
Children with oppositional 
defiant 
disorder are also at 
greater risk for both bullying peers and 
being bullied by peers. 



Genetic 
and 
physiological. 
A number of neurobiological 
markers (e.g., lower heart 
rate and skin 
conductance reactivity; 
reduced basal 
cortisol 
reactivity; 
abnormalities in the prefrontal 
cortex 
and amygdala) have been associated with oppositional 
defiant 
disorder. Studies have 
demonstrated overlapping genetic influences for the irritability and anger symptoms of 
oppositional 
defiant 
disorder with depression and generalized anxiety disorder. To date, the vast 
majority of studies have not 
separated children with oppositional 
defiant 
disorder from 
those 
with conduct 
disorder. Further study of markers specific to oppositional 
defiant 
disorder is 
needed. 


Culture-Related Diagnostic Issues 


The reported prevalence of oppositional 
defiant 
disorder or other disruptive disorders may be 
affected by misdiagnosis or overdiagnosis of individuals from 
some cultural 
backgrounds. Social 
norms may affect 
the prevalence of the disorder and its male gender predominance in children 
and adolescents. A meta-analysis of prevalence rates in middle childhood found that 
the disorder 
is more common in boys compared with girls in Western cultures, but 
that 
the prevalence is 
similar across genders in non-Western cultures. Also, despite adverse experiences, first-
generation migrants and refugees may be at 
decreased risk of developing oppositional 
defiant 
disorder symptoms. 


Sex- and Gender-Related Diagnostic Issues 


Some studies find few sex or gender differences for this disorder compared with, for example, 
conduct 
disorder. There may be slight 
differences in risk factors with harsh parenting more 
highly associated with oppositional defiant disorder in girls but not boys. 


Functional 
Consequences of Oppositional 
Defiant Disorder 


When oppositional 
defiant 
disorder is persistent 
throughout 
development, individuals with the 
disorder experience frequent 
conflicts with parents, teachers, supervisors, peers, and romantic 
partners. Such problems often result 
in significant 
impairments in the individual s emotional, 
social, academic, and occupational adjustment. 


Differential 
Diagnosis 


Conduct 
disorder. 
Conduct 
disorder and oppositional 
defiant 
disorder are both related to conduct 
problems that 
bring the individual 
in conflict 
with adults and other authority figures (e.g., 
teachers, work supervisors). The behaviors of oppositional 
defiant 
disorder are typically of a less 
severe nature than those of conduct 
disorder and do not 
include aggression toward people or 
animals, destruction of property, or a pattern of theft 
or deceit. However, evidence suggests that 
oppositional 
defiant 
disorder is associated with equivalent 
or even greater levels of impairment 
than conduct 
disorder. Furthermore, oppositional 
defiant 
disorder includes problems of emotion 
dysregulation (i.e., angry and irritable mood) that 
are not 
included in the definition of conduct 
disorder. 


Adjustment 
disorder. 
Environmental 
and family stressors may be associated with externalizing 
manifestations of emotion dysregulation. In children, these may manifest as 



526 


tantrums and oppositional 
behavior; 
and in adolescents, as aggressive behaviors (e.g., rebellion 
and defiance). Temporal 
association with a stressor and symptom 
duration of less than 6 months 
after the resolution of the stressor may help distinguish adjustment 
disorder from 
oppositional 
defiant disorder. 


Posttraumatic 
stress 
disorder. 
In children younger than 6 years, posttraumatic stress disorder may 
manifest 
initially as dysregulated behaviors, opposition, and tantrums; 
the association with a 
traumatic event 
and with other specific symptoms (traumatic play) are key to establishing the 
diagnosis. In adolescents, traumatic reenactment 
and risk-taking may be misinterpreted as 
defiance and opposition or as conduct problems. 


Attention-deficit/hyperactivity 
disorder. 
ADHD is often comorbid with oppositional defiant disorder. 
To make the additional 
diagnosis of oppositional 
defiant 
disorder, it 
is important 
to determine 
that 
the individual s failure to conform 
to requests of others is not 
solely in situations that 
demand sustained effort and attention or demand that the individual sit still. 


Depressive 
and 
bipolar disorders. 
Depressive and bipolar disorders often involve negative affect 
and irritability. As a result, a diagnosis of oppositional 
defiant 
disorder should not 
be made if the 
symptoms occur exclusively during the course of a mood disorder. 


Disruptive 
mood 
dysregulation 
disorder. 
Oppositional 
defiant 
disorder shares with disruptive mood 
dysregulation disorder the symptoms of chronic irritable mood and temper outbursts. However, if 
the irritable mood and other symptoms meet 
criteria for disruptive mood dysregulation disorder, 
a diagnosis of oppositional 
defiant 
disorder is not 
given, even if all 
criteria for oppositional 
defiant disorder are met. 


Intermittent 
explosive 
disorder. 
Intermittent 
explosive disorder also involves high rates of anger. 
However, individuals with this disorder show serious aggression toward others that 
is not 
part 
of 
the definition of oppositional defiant disorder. 


Intellectual 
developmental 
disorder (intellectual 
disability). 


In individuals with intellectual 
developmental 
disorder, a diagnosis of oppositional 
defiant disorder is given only if the 
oppositional 
behavior is markedly greater than is commonly observed among individuals of 
comparable mental age and with comparable severity of intellectual disability. 


Language 
disorder. 
Oppositional 
defiant 
disorder must 
also be distinguished from 
a failure to 


follow directions that is the result of impaired language comprehension (e.g., hearing loss). 
Social 
anxiety 
disorder. 
Oppositional 
defiant 
disorder must 
also be distinguished from 
defiance 
because of fear of negative evaluation associated with social anxiety disorder. 


Comorbidity 


Rates of oppositional 
defiant 
disorder are much higher in samples of children, adolescents, and 
adults with ADHD, and this may be the result 
of shared temperamental 
risk factors. Also, 
oppositional 
defiant 
disorder often precedes conduct 
disorder, although this appears to be most 
common in children with the childhood-onset 
subtype. Individuals with oppositional 
defiant 
disorder are also at 
increased risk for anxiety disorders and major depressive disorder, and this 
seems largely attributable to the presence of the angry-irritable mood symptoms. Extremely high 



rates of comorbidity between disruptive mood dysregulation disorder and symptoms 
characteristic of oppositional 
defiant 
disorder have been reported, with most 
individuals with 
disruptive mood dysregulation disorder having symptoms that 
meet 
criteria for oppositional 
defiant 
disorder (such as showing argumentative/defiant 
symptoms); 
but 
because oppositional 
defiant 
disorder cannot 
be diagnosed if criteria are also met 
for disruptive mood dysregulation 
disorder, only disruptive mood dysregulation disorder would be diagnosed in such cases. 
Adolescents and adults with oppositional 
defiant 
disorder also show a higher rate of substance 
use disorders, 


527 


although it is unclear if this association is independent of the comorbidity with conduct disorder. 


Intermittent Explosive Disorder 


Diagnostic Criteria 
F63.81 


A. 
Recurrent 
behavioral outbursts representing 
a 
failure 
to 
control aggressive 
impulses as manifested 
by either of 
the 
following: 
1. 
Verbal aggression 
(e.g., 
temper tantrums, 
tirades, 
verbal arguments or fights) 
or physical aggression 
toward 
property, 
animals, 
or other individuals, 
occurring 
twice 
weekly, 
on 
average, 
for a 
period 
of 
3 
months. 
The 
physical 
aggression 
does not 
result 
in 
damage 
or destruction 
of 
property and 
does not 
result 
in 
physical injury to 
animals or other individuals. 
2. 
Three 
behavioral outbursts involving 
damage 
or destruction 
of 
property 
and/or physical assault 
involving 
physical injury against 
animals or other 
individuals occurring 
within 
a 
12-month 
period. 
B. 
The 
magnitude 
of 
aggressiveness expressed 
during 
the 
recurrent 
outbursts is 
grossly out 
of 
proportion 
to 
the 
provocation 
or to 
any precipitating 
psychosocial 
stressors. 
C. 
The 
recurrent 
aggressive 
outbursts are 
not 
premeditated 
(i.e., 
they are 
impulsive 
and/or anger-based) and 
are 
not 
committed 
to 
achieve 
some 
tangible 
objective 
(e.g., 
money, 
power, 
intimidation). 
D. 
The 
recurrent 
aggressive 
outbursts cause 
either marked 
distress in 
the 
individual 
or impairment 
in 
occupational or interpersonal functioning, 
or are 
associated 
with 
financial or legal consequences. 
E. 
Chronological age 
is at 
least 
6 
years (or equivalent 
developmental level). 
F. 
The 
recurrent 
aggressive 
outbursts are 
not 
better explained 
by another mental 
disorder (e.g., 
major depressive 
disorder, 
bipolar disorder, 
disruptive 
mood 
dysregulation 
disorder, 
a 
psychotic disorder, 
antisocial personality disorder, 
borderline 
personality disorder) and 
are 
not 
attributable 
to 
another medical 
condition 
(e.g., 
head 
trauma, 
Alzheimer s disease) or to 
the 
physiological effects 

of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication). 
For children 
ages 6 18 
years, 
aggressive 
behavior that 
occurs as part 
of 
an 
adjustment 
disorder should 
not 
be 
considered 
for this diagnosis. 


Note: 
This diagnosis can 
be 
made 
in 
addition 
to 
the 
diagnosis of 
attentiondeficit/
hyperactivity disorder, 
conduct 
disorder, 
oppositional defiant 
disorder, 
or 
autism spectrum disorder when 
recurrent 
impulsive 
aggressive 
outbursts are 
in 
excess of 
those 
usually seen 
in 
these 
disorders and 
warrant 
independent 
clinical 
attention. 


Diagnostic Features 


The impulsive (or anger-based) aggressive outbursts in intermittent 
explosive disorder have a 
rapid onset 
and, typically, little or no prodromal 
period. Outbursts typically last 
for less than 30 
minutes and commonly occur in response to a minor provocation by a close intimate or associate. 
Individuals with intermittent 
explosive disorder often have less severe episodes of verbal 
or 
nondamaging, nondestructive, or noninjurious physical 
assault 
(Criterion A1) in between more 
severe destructive/assaultive episodes (Criterion A2). Criterion A1 defines frequent 
(i.e., twice 
weekly, on average, for a period of 3 months) aggressive outbursts characterized by temper 
tantrums, tirades, verbal 
arguments or fights, or assault 
without 
damage to objects or without 
injury to animals or other individuals. Criterion A2 defines infrequent 
(i.e., three in a 1-year 
period) impulsive aggressive outbursts characterized by damaging or destroying an object, 
regardless of its tangible value, or by 


528 


assaulting/striking or otherwise causing physical 
injury to an animal 
or to another individual. 
Regardless of the nature of the impulsive aggressive outburst, the core feature of intermittent 
explosive disorder is failure to control 
impulsive aggressive behavior in response to subjectively 
experienced provocation (i.e., psychosocial 
stressor) that 
would not 
typically result 
in an 
aggressive outburst 
(Criterion B). The aggressive outbursts are generally impulsive or anger-
based rather than premeditated or instrumental 
(Criterion C) and cause significant 
distress or 
impairment 
in occupational 
or interpersonal 
functioning or are associated with financial 
or legal 
consequences (Criterion D). A diagnosis of intermittent explosive disorder should not be given to 
individuals younger than 6 years, or the equivalent 
developmental 
level 
(Criterion E), or to 
individuals whose aggressive outbursts are better explained by another mental 
disorder (Criterion 
F). A diagnosis of intermittent 
explosive disorder should not 
be given to individuals with 
disruptive mood dysregulation disorder or to individuals whose impulsive aggressive outbursts 
are attributable to another medical 
condition or to the physiological 
effects of a substance 
(Criterion F). In addition, children ages 6 18 years should not 
receive this diagnosis when 
impulsive aggressive outbursts occur in the context of an adjustment disorder (Criterion F). 


Associated Features 


Depressive disorders, anxiety disorders, and substance use disorders are associated with 
intermittent 
explosive disorder, although onset 
of these disorders is typically later than that 
of 
intermittent explosive disorder. 



Research provides neurobiological 
support 
for the presence of serotonergic abnormalities, 
globally and in the brain, specifically in areas of the limbic system 
(anterior cingulate) and 
orbitofrontal 
cortex in individuals with intermittent 
explosive disorder. Amygdala responses to 
anger stimuli, during functional 
magnetic resonance imaging scanning, are greater in individuals 
with intermittent 
explosive disorder compared with healthy persons. In addition, the volume of 
gray matter in several 
frontolimbic regions is reduced and correlates inversely with measures of 
aggression in individuals with intermittent 
explosive disorder, although these brain differences 
are not always seen. 


Prevalence 


The 1-year prevalence for intermittent explosive disorder in the United States is about 2.6%, with 
a lifetime prevalence of 4.0%. Higher 1-year prevalences of 3.9% and 6.9% (narrow definition) 
are present 
among African Americans and Caribbean Black adolescents, respectively, in the 
United States, especially among males. This is consistent 
with higher 12-month rates of 
psychiatric disorder among immigrant 
Caribbean Black men and their second-and third-
generation offspring, possibly associated with downward social 
mobility and the effects of 
racism. However, the reported prevalence of conduct 
disorder or other disruptive disorders may 
be affected by misdiagnosis or overdiagnosis of individuals from 
some cultural 
backgrounds. 
Intermittent 
explosive disorder is more prevalent 
among younger individuals (e.g., younger than 
35 40 years), compared with individuals older than 50 years, and individuals with a high school 
education or less. In some studies, the prevalence of intermittent 
explosive disorder is greater in 
men and boys than in women and girls; other studies have found no sex or gender differences. 


Development and Course 


The onset 
of recurrent, problematic, impulsive aggressive behavior is most 
common in late 
childhood or adolescence and rarely begins for the first 
time after age 40 years. The course of the 
disorder may be episodic, with recurrent 
periods of impulsive aggressive outbursts. Intermittent 
explosive disorder appears to follow a chronic and persistent 
course over many years. It 
also 
appears to be quite common regardless of the presence or absence of 


529 


attention-deficit/hyperactivity disorder (ADHD) or other disruptive, impulse-control, and 
conduct disorders (e.g., conduct disorder, oppositional defiant disorder). 


Risk and Prognostic Factors 


Environmental. 
Individuals with a history of physical 
and emotional 
trauma during the first 
20 
years of life are at 
increased risk for intermittent 
explosive disorder. Long-term 
displacement 
from 
home and separation from 
family members are risk factors in some refugee population 
settings. 


Genetic 
and 
physiological. 
First-degree relatives of individuals with intermittent 
explosive 
disorder are at 
increased risk for intermittent 
explosive disorder, and twin studies have 
demonstrated a substantial genetic influence for impulsive aggression. 



Culture-Related Diagnostic Issues 


The lower prevalence of intermittent 
explosive disorder in some regions (Asia, Middle East) or 
countries (Romania, Nigeria), compared with the United States, suggests that 
information about 
recurrent, problematic, impulsive aggressive behaviors either is not 
elicited on questioning or is 
less likely to be present, because of cultural factors. 


Association With Suicidal 
Thoughts or Behavior 


A study of 1,460 research volunteers found that 
intermittent 
explosive disorder comorbid with 
posttraumatic stress disorder was associated with a markedly elevated rate of lifetime suicide 
attempt 
(41%). Posttraumatic stress disorder and intermittent 
explosive disorder were the only 
disorders associated with suicide attempt 
among soldiers with suicidal 
ideation, although the role 
of intermittent explosive disorder was less clear in multivariate analyses. 


Functional 
Consequences of Intermittent Explosive Disorder 


Social 
(e.g., loss of friends, relatives, marital 
instability), occupational 
(e.g., demotion, loss of 
employment), financial 
(e.g., because of value of objects destroyed), and legal 
(e.g., civil 
suits as 
a result 
of aggressive behavior against 
person or property; 
criminal 
charges for assault) problems 
often develop as a result of intermittent explosive disorder. 


Differential 
Diagnosis 


A diagnosis of intermittent 
explosive disorder should not 
be made when Criteria A1 and/or A2 
are only met 
during an episode of another mental 
disorder (e.g., major depressive disorder, 
bipolar disorder, psychotic disorder), or when impulsive aggressive outbursts are attributable to 
another medical 
condition or to the physiological 
effects of a substance or medication. This 
diagnosis also should not 
be made, particularly in children and adolescents ages 6 18 years, 
when the impulsive aggressive outbursts occur in the context of an adjustment disorder. 


Disruptive 
mood 
dysregulation 
disorder. 
In contrast 
to intermittent 
explosive disorder, disruptive 
mood dysregulation disorder is characterized by a persistently negative mood state (i.e., 
irritability, anger) most 
of the day, nearly every day, between impulsive aggressive outbursts. A 
diagnosis of disruptive mood dysregulation disorder can only be given when the onset 
of 
recurrent, problematic, impulsive aggressive outbursts is before age 10 years. Finally, a diagnosis 
of disruptive mood dysregulation disorder should not 
be made for the first 
time after age 18 
years. Otherwise, these diagnoses are mutually exclusive. 


Antisocial 
personality 
disorder or borderline 
personality 
disorder. 


Individuals with antisocial 
personality disorder or borderline personality disorder often display recurrent, 


530 


problematic impulsive aggressive outbursts. However, the level 
of impulsive aggression in 
individuals with antisocial 
personality disorder or borderline personality disorder is lower than 
that in individuals with intermittent explosive disorder. 



Delirium, 
major neurocognitive 
disorder, 
and 
personality 
change 
due 
to 
another medical 
condition, 
aggressive 
type. 


A diagnosis of intermittent 
explosive disorder should not 
be made when aggressive outbursts are 
judged to result 
from 
the physiological 
effects of another diagnosable medical 
condition (e.g., 
brain injury associated with a change in personality characterized by aggressive outbursts; 
complex partial 
epilepsy). Nonspecific abnormalities on neurological 
examination (e.g.,  soft 
signs ) and nonspecific electroencephalographic changes are compatible with a diagnosis of 
intermittent 
explosive disorder unless there is a diagnosable medical 
condition that 
better 
explains the impulsive aggressive outbursts. 
Substance 
intoxication 
or substance 
withdrawal. 
A diagnosis of intermittent 
explosive disorder 


should not 
be made when impulsive aggressive outbursts are nearly always associated with 
intoxication with or withdrawal 
from 
substances (e.g., alcohol, phencyclidine, cocaine and other 
stimulants, barbiturates, inhalants). However, when a sufficient 
number of impulsive aggressive 
outbursts also occur in the absence of substance intoxication or withdrawal, and these warrant 
independent clinical attention, a diagnosis of intermittent explosive disorder may be given. 


Attention-deficit/hyperactivity 
disorder, 
conduct 
disorder, 
oppositional 
defiant 
disorder, 
or 
autism spectrum disorder. 


Individuals with any of these childhood-onset 
disorders may exhibit 
impulsive aggressive 
outbursts. Individuals with ADHD are typically impulsive and, as a result, may also exhibit 
impulsive aggressive outbursts. While individuals with conduct 
disorder can exhibit 
impulsive 
aggressive outbursts, the form 
of aggression characterized by the diagnostic criteria is proactive 
and predatory. Aggression in oppositional 
defiant 
disorder is typically characterized by temper 
tantrums and verbal 
arguments with authority figures, whereas impulsive aggressive outbursts in 
intermittent 
explosive disorder are in response to a broader array of provocation and include 
physical 
assault. The level 
of impulsive aggression in individuals with a history of one or more 
of these disorders has been reported as lower than that 
in comparable individuals whose 
symptoms also meet 
intermittent 
explosive disorder Criteria A through E. Accordingly, if 
Criteria A through E 
are also met, and the impulsive aggressive outbursts warrant 
independent 
clinical attention, a diagnosis of intermittent explosive disorder may be given. 


Comorbidity 


Depressive disorders, anxiety disorders, posttraumatic stress disorder, bulimia nervosa, binge-
eating disorder, and substance use disorders are most 
commonly comorbid with intermittent 
explosive disorder in community samples. In addition, individuals with antisocial 
personality 
disorder or borderline personality disorder, and individuals with a history of disorders with 
disruptive behaviors (e.g., ADHD, conduct 
disorder, oppositional 
defiant 
disorder), are at 
greater 
risk for comorbid intermittent explosive disorder. 


Conduct Disorder 


Diagnostic Criteria 


A. 
A 
repetitive 
and 
persistent 
pattern 
of 
behavior in 
which 
the 
basic rights of 
others 

or major age-appropriate 
societal norms or rules are 
violated, 
as manifested 
by 
the 
presence 
of 
at 
least 
three 
of 
the 
following 
15 
criteria 
in 
the 
past 
12 
months 
from any of 
the 
categories below, 
with 
at 
least 
one 
criterion 
present 
in 
the 
past 
6 
months: 


531 


Aggression 
to 
People 
and 
Animals 


1. 
Often 
bullies, 
threatens, 
or intimidates others. 
2. 
Often 
initiates physical fights. 
3. 
Has used 
a 
weapon 
that 
can 
cause 
serious physical harm to 
others (e.g., 
a 
bat, 
brick, 
broken 
bottle, 
knife, 
gun). 
4. 
Has been 
physically cruel to 
people. 
5. 
Has been 
physically cruel to 
animals. 
6. 
Has stolen 
while 
confronting 
a 
victim (e.g., 
mugging, 
purse 
snatching, 
extortion, 
armed 
robbery). 
7. 
Has forced 
someone 
into 
sexual activity. 
Destruction 
of Property 


8. 
Has deliberately engaged 
in 
fire 
setting 
with 
the 
intention 
of 
causing 
serious 
damage. 
9. 
Has deliberately destroyed 
others  property (other than 
by fire 
setting). 
Deceitfulness 
or Theft 


10. 
Has broken 
into 
someone 
else s house, 
building, 
or car. 
11. 
Often 
lies to 
obtain 
goods or favors or to 
avoid 
obligations (i.e., 
 cons  
others). 
12. 
Has stolen 
items of 
nontrivial value 
without 
confronting 
a 
victim (e.g., 
shoplifting, 
but 
without 
breaking 
and 
entering; 
forgery). 
Serious 
Violations 
of Rules 


13. 
Often 
stays out 
at 
night 
despite 
parental prohibitions, 
beginning 
before 
age 
13 
years. 
14. 
Has run 
away from home 
overnight 
at 
least 
twice 
while 
living 
in 
the 
parental 
or parental surrogate 
home, 
or once 
without 
returning 
for a 
lengthy period. 
15. 
Is often 
truant 
from school, 
beginning 
before 
age 
13 
years. 
B. 
The 
disturbance 
in 
behavior causes clinically significant 
impairment 
in 
social, 
academic, 
or occupational functioning. 
C. 
If 
the 
individual is age 
18 
years or older, 
criteria 
are 
not 
met 
for antisocial 
personality disorder. 
Specify 
whether: 
F91.1 
Childhood-onset type: 
Individuals show at 
least 
one 
symptom 
characteristic of 
conduct 
disorder prior to 
age 
10 
years. 


F91.2 
Adolescent-onset type: 
Individuals show no 
symptom characteristic of 



conduct 
disorder prior to 
age 
10 
years. 
F91.9 
Unspecified 
onset: 
Criteria 
for a 
diagnosis of 
conduct 
disorder are 
met, 
but 
there 
is not 
enough 
information 
available 
to 
determine 
whether the 
onset 
of 
the 
first 
symptom was before 
or after age 
10 
years. 


Specify 
if: 
With 
limited 
prosocial 
emotions: 
To 
qualify for this specifier, 
an 
individual 
must 
have 
displayed 
at 
least 
two 
of 
the 
following 
characteristics persistently over 
at 
least 
12 
months and 
in 
multiple 
relationships and 
settings. 
These 
characteristics reflect 
the 
individual s typical pattern 
of 
interpersonal and 
emotional functioning 
over this period 
and 
not 
just 
occasional occurrences in 
some 
situations. 
Thus, 
to 
assess the 
criteria 
for the 
specifier, 
multiple 
information 
sources are 
necessary. 
In 
addition 
to 
the 
individual s self-report, 
it 
is necessary 
to 
consider reports by others who 
have 
known 
the 
individual for extended 
periods of 
time 
(e.g., 
parents, 
teachers, 
co-workers, 
extended 
family members, 
peers). 


532 


Lack 
of remorse 
or guilt: 
Does not 
feel bad 
or guilty when 
he 
or she 
does 
something 
wrong 
(exclude 
remorse 
when 
expressed 
only when 
caught 
and/or 
facing 
punishment). 
The 
individual shows a 
general lack of 
concern 
about 
the 
negative 
consequences of 
his or her actions. 
For example, 
the 
individual is not 
remorseful after hurting 
someone 
or does not 
care 
about 
the 
consequences of 
breaking 
rules. 


Callous lack 
of empathy: 
Disregards and 
is unconcerned 
about 
the 
feelings 
of 
others. 
The 
individual is described 
as cold 
and 
uncaring. 
The 
individual 
appears more 
concerned 
about 
the 
effects of 
his or her actions on 
himself 
or 
herself, 
rather than 
their effects on 
others, 
even 
when 
they result 
in 
substantial 
harm to 
others. 


Unconcerned 
about performance: 
Does not 
show concern 
about 
poor/problematic performance 
at 
school, 
at 
work, 
or in 
other important 
activities. 
The 
individual does not 
put 
forth 
the 
effort 
necessary to 
perform well, 
even 
when 
expectations are 
clear, 
and 
typically blames others for his or her 
poor performance. 


Shallow 
or deficient affect: 
Does not 
express feelings or show emotions to 
others, 
except 
in 
ways that 
seem shallow, 
insincere, 
or superficial (e.g., 
actions contradict 
the 
emotion 
displayed; 
can 
turn 
emotions  on  or  off  
quickly) or when 
emotional expressions are 
used 
for gain 
(e.g., 
emotions 
displayed 
to 
manipulate 
or intimidate 
others). 


Specify 
current 
severity: 
Mild: 
Few if 
any conduct 
problems in 
excess of 
those 
required 
to 
make 
the 
diagnosis are 
present, 
and 
conduct 
problems cause 
relatively minor harm to 
others (e.g., 
lying, 
truancy, 
staying 
out 
after dark without 
permission, 
other rule 



breaking). 
Moderate: 
The 
number of 
conduct 
problems and 
the 
effect 
on 
others are 


intermediate 
between 
those 
specified 
in 
 mild  and 
those 
in 
 severe  (e.g., 
stealing 
without 
confronting 
a 
victim, 
vandalism). 
Severe: 
Many conduct 
problems in 
excess of 
those 
required 
to 
make 
the 


diagnosis are 
present, 
or conduct 
problems cause 
considerable 
harm to 
others 
(e.g., 
forced 
sex, 
physical cruelty, 
use 
of 
a 
weapon, 
stealing 
while 
confronting 
a 
victim, 
breaking 
and 
entering). 


Subtypes 


Three subtypes of conduct 
disorder are provided based on the age at 
onset 
of the disorder. Both 
childhood-onset and adolescent-onset subtypes can occur in a mild, moderate, or severe form. An 
unspecified-onset 
subtype is designated when there is insufficient 
information to determine age 
at onset. 


In childhood-onset 
conduct 
disorder, individuals are usually male, have disturbed peer 
relationships, may have had oppositional 
defiant 
disorder during early childhood, and usually 
have symptoms that 
meet 
full 
criteria for conduct 
disorder prior to puberty. Individuals with the 
childhood-onset 
type may be more likely to display aggression toward others than individuals 
with the adolescent-onset 
type. Many children with this subtype also have concurrent 
attentiondeficit/
hyperactivity disorder (ADHD) or other neurodevelopmental 
difficulties. Individuals with 
childhood-onset 
type are more likely to have persistent 
conduct 
disorder into adulthood than are 
those with adolescent-onset 
type. Individuals with adolescent-onset 
conduct 
disorder tend to 
have more normative peer relationships (although they often display conduct 
problems in the 
company of others). 


Specifiers 


A minority of individuals with conduct 
disorder exhibit 
characteristics that 
qualify for the  with 
limited prosocial 
emotions  specifier. The indicators of this specifier are those that 
have often 
been labeled as callous and unemotional 
traits in research. Other personality features, such as 
thrill 
seeking, fearlessness, and insensitivity to punishment, may also distinguish those with 
characteristics described in the specifier. Individuals with 


533 


characteristics described in this specifier may be more likely than other individuals with conduct 
disorder to engage in aggression that 
is planned for instrumental 
gain. Individuals with conduct 
disorder of any subtype or any level 
of severity can have characteristics that 
qualify for the 
specifier  with limited prosocial 
emotions,  although individuals with the specifier are more 
likely to have childhood-onset type and a severity specifier rating of severe. 


Although the validity of self-report 
to assess the presence of the specifier has been supported 
in some research contexts, individuals with conduct 
disorder with this specifier may not 
readily 
admit 
to the traits in a clinical 
interview. Thus, to assess the criteria for the specifier, multiple 
information sources are necessary. Also, because the indicators of the specifier are characteristics 



that 
reflect 
the individual s typical 
pattern of interpersonal 
and emotional 
functioning, it 
is 
important 
to consider reports by others who have known the individual 
for extended periods of 
time and across relationships and settings (e.g., parents, teachers, co-workers, extended family 
members, peers). 


Diagnostic Features 


The essential 
feature of conduct 
disorder is a repetitive and persistent 
pattern of behavior in 
which the basic rights of others or major age-appropriate societal 
norms or rules are violated 
(Criterion A). These behaviors fall 
into four main groupings: 
aggressive conduct 
that 
causes or 
threatens physical 
harm 
to other people or animals (Criteria A1 A7); 
nonaggressive conduct 
that 
causes property loss or damage (Criteria A8 A9); 
deceitfulness or theft 
(Criteria A10 A12); 
and 
serious violations of rules (Criteria A13 A15). Three or more characteristic behaviors must 
have 
been present 
during the past 
12 months, with at 
least 
one behavior present 
in the past 
6 months. 
The disturbance in behavior causes clinically significant 
impairment 
in social, academic, or 
occupational 
functioning (Criterion B). The behavior pattern is usually present 
in a variety of 
settings, such as home, at 
school, or in the community. Because individuals with conduct 
disorder are likely to minimize their conduct problems, the clinician often must rely on additional 
informants. However, informants  knowledge of the individual s conduct 
problems may be 
limited if they have inadequately supervised the individual 
or the individual 
has concealed 
symptom behaviors. 


Individuals with conduct 
disorder often initiate aggressive behavior and react 
aggressively to 
others. They may display bullying, threatening, or intimidating behavior (including bullying via 
messaging on web-based social 
media) (Criterion A1); 
initiate frequent 
physical 
fights (Criterion 
A2); 
use a weapon that 
can cause serious physical 
harm 
(e.g., a bat, brick, broken bottle, knife, 
gun) (Criterion A3); 
be physically cruel 
to people (Criterion A4) or animals (Criterion A5); 
steal 
while confronting a victim 
(e.g., mugging, purse snatching, extortion, armed robbery) (Criterion 
A6); 
or force someone into sexual 
activity (Criterion A7). Physical 
violence may take the form 
of rape, assault, or, in rare cases, homicide. Deliberate destruction of others  property may 
include deliberate fire setting with the intention of causing serious damage (Criterion A8) or 
deliberate destroying of other people s property in other ways (e.g., smashing car windows, 
vandalizing school 
property) (Criterion A9). Acts of deceitfulness or theft 
may include breaking 
into someone else s house, building, or car (Criterion A10); 
frequently lying or breaking 
promises to obtain goods or favors or to avoid debts or obligations (e.g.,  conning  other 
individuals) (Criterion A11); 
or stealing items of nontrivial 
value without 
confronting the victim 
(e.g., shoplifting, forgery, fraud) (Criterion A12). 


Individuals with conduct 
disorder may also frequently commit 
serious violations of rules 
(e.g., school, parental, workplace). Children with conduct 
disorder often have a pattern, 
beginning before age 13 years, of staying out 
late at 
night 
despite parental 
prohibitions (Criterion 
A13). Children may also show a pattern of running away from 
home overnight 
(Criterion A14). 
To be considered a symptom 
of conduct 
disorder, the running away must 
have occurred at 
least 
twice (or only once if the individual 
did not 
return for a lengthy period). Runaway episodes that 
occur as a direct 
consequence of physical 
or sexual 
abuse do not 
typically qualify for this 
criterion. Children with conduct 
disorder may often be truant 
from 
school, beginning prior to age 
13 years (Criterion A15). 



534 


Associated Features 


Especially in ambiguous situations, aggressive individuals with conduct 
disorder frequently 
misperceive the intentions of others as more hostile and threatening than is the case and respond 
with aggression that 
they then feel 
is reasonable and justified. Personality features of trait 
negative emotionality and poor self-control, including poor frustration tolerance, irritability, 
temper outbursts, suspiciousness, insensitivity to punishment, thrill 
seeking, and recklessness, 
frequently co-occur with conduct 
disorder. Substance misuse is often an associated feature, 
particularly in adolescent girls. 


Prevalence 


One-year population prevalence estimates in the United States and other largely high-income 
countries range from 
2% to more than 10%, with a median of 4%. In the United States, the 
lifetime prevalence was found to be 12.0% among men and 7.1% among women. The prevalence 
of conduct 
disorder in largely Western samples appears to be fairly consistent 
across various 
countries. Prevalence rates rise from 
childhood to adolescence. Prevalence of adolescent-onset 
conduct disorder is more frequently associated with psychosocial stressors for example, being a 
member of a socially oppressed ethnic group facing discrimination. Few children with impairing 
conduct disorder receive treatment. 


Development and Course 


The onset 
of conduct 
disorder may occur as early as the preschool 
years, but 
the first 
significant 
symptoms usually emerge during the period from 
middle childhood through middle adolescence. 
Oppositional 
defiant 
disorder is a common precursor to the childhood-onset 
type of conduct 
disorder. Physically aggressive symptoms are more common than nonaggressive symptoms 
during childhood, but 
nonaggressive symptoms become more common than aggressive 
symptoms during adolescence. 


Conduct 
disorder may be diagnosed in adults; 
however, symptoms of conduct 
disorder 
usually emerge in childhood or adolescence, and onset 
is rare after age 16 years. The course of 
conduct 
disorder after onset 
is variable. In a majority of individuals, the disorder remits by 
adulthood. Many individuals with conduct 
disorder particularly those with adolescent-onset 
type and those with few and milder symptoms achieve adequate social 
and occupational 
adjustment 
as adults. However, the childhood-onset 
type predicts a worse prognosis and an 
increased risk of criminal 
behavior, conduct 
disorder, and substance-related disorders in 
adulthood. Individuals with conduct 
disorder are at 
risk for later mood disorders, anxiety 
disorders, posttraumatic stress disorder, impulse-control 
disorders, psychotic disorders, somatic 
symptom disorders, and substance-related disorders as adults. 


Symptoms of the disorder vary with age as the individual 
develops increased physical 
strength, cognitive abilities, and sexual 
maturity. Symptom 
behaviors that 
emerge first 
tend to be 
less serious (e.g., lying, shoplifting), whereas conduct 
problems that 
emerge last 
tend to be more 
severe (e.g., rape, theft 
while confronting a victim). However, there are wide differences among 
individuals, with some engaging in the more damaging behaviors at 
an early age (which is 



predictive of a worse prognosis). When individuals with conduct 
disorder reach adulthood, 
symptoms of aggression, property destruction, deceitfulness, and rule violation, including 
violence against 
co-workers, partners, and children, may be exhibited in the workplace and the 
home, such that antisocial personality disorder may be considered. 


Risk and Prognostic Factors 


Temperamental. 
Temperamental 
risk factors include a difficult 
undercontrolled infant 


temperament and lower-than-average intelligence, particularly with regard to verbal IQ. 
Environmental. 
Family-level 
risk factors include parental 
rejection and neglect, inconsistent 
child-rearing practices, harsh discipline, physical or sexual abuse, lack of supervision, 


535 


early institutional 
living, frequent 
changes of caregivers, large family size, parental 
criminality, 
and certain kinds of familial 
psychopathology (e.g., substance-related disorders). Community-
level 
risk factors include peer rejection, association with a delinquent 
peer group, neighborhood 
disadvantage, and exposure to violence. Both types of risk factors tend to be more common and 
severe among individuals with the childhood-onset 
subtype of conduct 
disorder. On the other 
hand, parental 
migration is a risk factor for children who are left 
in the country of origin as well 
as for those who migrated with their parents, with conduct 
problems being attributable to 
acculturation processes. Nevertheless, first-generation immigrants and refugees often have fewer 
conduct problems than their peers. 


Genetic 
and 
physiological. 
Conduct 
disorder is influenced by both genetic and environmental 
factors. Genetic associations may be stronger for aggressive symptoms. The risk is increased in 
children with a biological 
or adoptive parent 
or a sibling with conduct 
disorder. The disorder also 
appears to be more common in children of biological 
parents with severe alcohol 
use disorder, 
depressive and bipolar disorders, or schizophrenia or biological 
parents who have a history of 
ADHD or conduct 
disorder. Family history particularly characterizes individuals with the 
childhood-onset 
subtype of conduct 
disorder. Slower resting heart 
rate has been reliably noted in 
individuals with conduct 
disorder compared with those without 
the disorder, and this marker is 
not 
characteristic of any other mental 
disorder. Reduced autonomic fear conditioning, 
particularly low skin conductance, is also well 
documented. However, these psychophysiological 
findings are not 
diagnostic of the disorder. Structural 
and functional 
differences in brain areas 
associated with affect 
regulation and affect 
processing, particularly frontotemporal-limbic 
connections involving the brain s ventral 
prefrontal 
cortex and amygdala, have been consistently 
noted in individuals with conduct 
disorder compared with those without 
the disorder. However, 
neuroimaging findings are not diagnostic of the disorder. 


Course 
modifiers. 
Persistence is more likely for individuals with behaviors that 
meet 
criteria for 
the childhood-onset 
subtype and qualify for the specifier  with limited prosocial 
emotions.  The 
risk that 
conduct 
disorder will 
persist 
is also increased by co-occurring ADHD and by substance 
abuse. 


Culture-Related Diagnostic Issues 



Conduct 
disorder diagnosis may at 
times be misapplied to individuals in settings where patterns 
of disruptive behavior are viewed as near-normative (e.g., in very threatening, high-crime areas 
or war zones). Therefore, the context in which the undesirable behaviors have occurred should be 
considered. In youth from 
underserved ethnic and racialized groups, reactions to racism 
that 
involve anger and resistance-based coping may be misdiagnosed as conduct 
disorder by 
uninformed practitioners, as suggested by the association between experiences of discrimination 
and adolescent-onset conduct disorder in these groups. 


Sex- and Gender-Related Diagnostic Issues 


Boys and men with a diagnosis of conduct 
disorder frequently exhibit 
fighting, stealing, 
vandalism, and school 
discipline problems. Girls and women with a diagnosis of conduct 
disorder are more likely to exhibit 
lying, truancy, running away, and prostitution. Whereas boys 
and men and girls and women exhibit 
relational 
aggression (behavior that 
harms social 
relationships of others), girls and women exhibit 
considerably less physical 
aggression than do 
boys and men. 


Association With Suicidal 
Thoughts or Behavior 


Suicidal 
thoughts, suicide attempts, and suicide occur at 
a higher-than-expected rate in 
individuals with conduct 
disorder. A large study conducted in Taiwan that 
followed adolescents 
with conduct disorder over 10 years found that conduct disorder was associated 


536 


with a higher rate of suicide attempts even after adjustment 
for comorbid mood, anxiety, and 
substance use disorders. 


Functional 
Consequences of Conduct Disorder 


Conduct 
disorder behaviors may lead to school 
suspension or expulsion, problems in work 
adjustment, legal 
difficulties, sexually transmitted diseases, unplanned pregnancy, and physical 
injury from 
accidents or fights. These problems may preclude attendance in ordinary schools or 
living in a parental 
or foster home. Conduct 
disorder is often associated with an early onset 
of 
sexual 
behavior, alcohol 
use, tobacco smoking, use of illegal 
substances, and reckless and risk-
taking acts. Accident 
rates appear to be higher among individuals with conduct 
disorder 
compared with those without 
the disorder. These functional 
consequences of conduct 
disorder 
may increase the risk for health difficulties when individuals reach midlife. It 
is not 
uncommon 
for individuals with conduct 
disorder to come into contact 
with the criminal 
justice system 
for 
engaging in illegal 
behavior. Conduct 
disorder is a common reason for treatment 
referral 
and is 
frequently diagnosed in mental 
health facilities for children, especially in forensic practice. It 
is 
associated with impairment 
that 
is more severe and chronic than that 
experienced by other clinic-
referred children. 


Differential 
Diagnosis 


Oppositional 
defiant 
disorder. 
Conduct 
disorder and oppositional 
defiant 
disorder are both related 



to symptoms that 
bring the individual 
in conflict 
with adults and other authority figures (e.g., 
parents, teachers, work supervisors). The behaviors of oppositional 
defiant 
disorder are typically 
of a less severe nature than those of individuals with conduct 
disorder and do not 
include 
aggression toward people or animals, destruction of property, or a pattern of theft 
or deceit. 
Furthermore, oppositional 
defiant 
disorder includes problems of emotion dysregulation (i.e., 
angry and irritable mood) that 
are not 
included in the definition of conduct 
disorder. When 
criteria are met 
for both oppositional 
defiant 
disorder and conduct 
disorder, both diagnoses can 
be given. 


Attention-deficit/hyperactivity 
disorder. 
Although children with ADHD often exhibit 
hyperactive 
and impulsive behavior that 
may be disruptive, this behavior does not 
by itself violate societal 
norms or the rights of others and therefore does not 
usually meet 
criteria for conduct 
disorder. 
When criteria are met for both ADHD and conduct disorder, both diagnoses should be given. 


Depressive 
and 
bipolar disorders. 
Irritability, aggression, and conduct 
problems can occur in 
children or adolescents with major depressive disorder, bipolar disorder, or disruptive mood 
dysregulation disorder. The behavioral 
problems associated with these mood disorders can 
usually be distinguished from 
the pattern of conduct 
problems seen in conduct 
disorder based on 
their course. Specifically, individuals with conduct 
disorder will 
display substantial 
levels of 
aggressive or nonaggressive conduct 
problems during periods in which there is no mood 
disturbance, either historically (i.e., a history of conduct 
problems predating the onset 
of the 
mood disturbance) or concurrently (i.e., display of some conduct 
problems that 
are premeditated 
and do not 
occur during periods of intense emotional 
arousal). In those cases in which criteria for 
conduct disorder and a mood disorder are met, both diagnoses can be given. 


Intermittent 
explosive 
disorder. 
Both conduct 
disorder and intermittent 
explosive disorder involve 
high rates of aggression. However, the aggression in individuals with intermittent 
explosive 
disorder is limited to impulsive aggression and is not 
premeditated, and it 
is not 
committed in 
order to achieve some tangible objective (e.g., money, power, intimidation). Also, the definition 
of intermittent 
explosive disorder does not 
include the non-aggressive symptoms of conduct 
disorder. If criteria for both disorders are met, the diagnosis of intermittent 
explosive disorder 
should be given only when the recurrent 
impulsive aggressive outbursts warrant 
independent 
clinical attention. 


537 


Adjustment 
disorders. 
The diagnosis of an adjustment 
disorder (with disturbance of conduct 
or 
with mixed disturbance of emotions and conduct) should be considered if clinically significant 
conduct 
problems that 
do not 
meet 
the criteria for another specific disorder develop in clear 
association with the onset 
of a psychosocial 
stressor and do not 
resolve within 6 months of the 
termination of the stressor (or its consequences). Conduct 
disorder is diagnosed only when the 
conduct 
problems represent 
a repetitive and persistent 
pattern that 
is associated with impairment 
in social, academic, or occupational functioning. 


Comorbidity 


ADHD and oppositional 
defiant 
disorder are both common in individuals with conduct 
disorder, 
and this comorbid presentation predicts worse outcomes. Individuals who show the personality 



features associated with antisocial 
personality disorder often violate the basic rights of others or 
violate major age-appropriate societal 
norms, and as a result 
their pattern of behavior often meets 
criteria for conduct 
disorder. Conduct 
disorder may also co-occur with one or more of the 
following mental 
disorders: 
specific learning disorder, anxiety disorders, depressive or bipolar 
disorders, and substance-related disorders. Academic achievement, particularly in reading and 
other verbal 
skills, is often below the level 
expected on the basis of age and intelligence and may 
justify the additional diagnosis of specific learning disorder or a communication disorder. 


Antisocial 
Personality Disorder 


Criteria and text 
for antisocial 
personality disorder can be found in the chapter  Personality 
Disorders.  Because this disorder is closely connected to the spectrum 
of  externalizing  conduct 
disorders in this chapter, as well 
as to the disorders in the adjoining chapter  Substance-Related 
and Addictive Disorders,  it is listed here as well as in the chapter  Personality Disorders.  


Pyromania 


Diagnostic Criteria 
F63.1 


A. 
Deliberate 
and 
purposeful fire 
setting 
on 
more 
than 
one 
occasion. 
B. 
Tension 
or affective 
arousal before 
the 
act. 
C. 
Fascination 
with, 
interest 
in, 
curiosity about, 
or attraction 
to 
fire 
and 
its situational 
contexts (e.g., 
paraphernalia, 
uses, 
consequences). 
D. 
Pleasure, 
gratification, 
or relief 
when 
setting 
fires or when 
witnessing 
or 
participating 
in 
their aftermath. 
E. 
The 
fire 
setting 
is not 
done 
for monetary gain, 
as an 
expression 
of 
sociopolitical 
ideology, 
to 
conceal criminal activity, 
to 
express anger or vengeance, 
to 
improve 
one s living 
circumstances, 
in 
response 
to 
a 
delusion 
or hallucination, 
or as a 
result 
of 
impaired 
judgment 
(e.g., 
in 
major neurocognitive 
disorder, 
intellectual 
developmental disorder [intellectual disability], 
substance 
intoxication). 
F. 
The 
fire 
setting 
is not 
better explained 
by conduct 
disorder, 
a 
manic episode, 
or 
antisocial personality disorder. 
Diagnostic Features 


The essential 
feature of pyromania is the presence of multiple episodes of deliberate and 
purposeful 
fire setting (Criterion A). Individuals with this disorder experience tension or 
affective arousal before setting a fire (Criterion B). There is a fascination with, interest in, 


538 


curiosity about, or attraction to fire and its situational 
contexts (e.g., paraphernalia, uses, 



consequences) (Criterion C). Individuals with this disorder are often regular  watchers  at 
fires 
in their neighborhoods, may set 
off false alarms, and derive pleasure from 
institutions, 
equipment, and personnel 
associated with fire. They may spend time at 
the local 
fire department, 
set 
fires to be affiliated with the fire department, or even become firefighters. Individuals with 
this disorder experience pleasure, gratification, or relief when setting the fire, witnessing its 
effects, or participating in its aftermath (Criterion D). The fire setting is not 
done for monetary 
gain, as an expression of sociopolitical 
ideology, to conceal 
criminal 
activity, to express anger or 
vengeance, to improve one s living circumstances, or in response to a delusion or a hallucination 
(Criterion E). The fire setting does not 
result 
from 
impaired judgment 
(e.g., in major 
neurocognitive disorder or intellectual 
developmental 
disorder [intellectual 
disability]). The 
diagnosis is not 
made if the fire setting is better explained by conduct 
disorder, a manic episode, 
or antisocial personality disorder (Criterion F). 


Associated Features 


Individuals with pyromania may make considerable advance preparation for starting a fire. They 
may be indifferent 
to the consequences to life or property caused by the fire, or they may derive 
satisfaction from 
the resulting property destruction. The behaviors may lead to property damage, 
legal 
consequences, or injury or loss of life to the fire setter or to others. Individuals who 
impulsively set 
fires (who may or may not 
have pyromania) often have a current 
or past 
history 
of alcohol use disorder. 


Prevalence 


The population prevalence of pyromania is not 
known. The lifetime prevalence of fire-setting 
behavior, which is just 
one component 
of pyromania and not 
sufficient 
for a diagnosis by itself, 
was reported as 1.0% 1.1% in a population sample. Fire-setting behavior occurs more often in 
men than in women (lifetime prevalence 1.7% vs. 0.4%); 
however, whether this also holds true 
for pyromania is unknown. The most 
common comorbidities of fire-setting behavior were 
antisocial 
personality disorder, substance use disorder, bipolar disorder, and gambling disorder. 
In contrast 
to fire setting, pyromania as a primary diagnosis appears to be very rare. Among a 
sample of persons in a Finnish hospital 
reaching the criminal 
system 
because of repeated fire 
setting, only 3.3% had symptoms that 
met 
full 
criteria for pyromania. In a U.S. study, 3.4% of a 
sample of adults hospitalized for psychiatric reasons had symptoms that 
met 
full 
criteria for 
current pyromania. 


Development and Course 


Although data are limited, some research suggests that 
late adolescence may be the typical 
age at 
onset 
of pyromania. The relationship between fire setting in childhood and pyromania in 
adulthood has not 
been documented. In individuals with pyromania, fire-setting incidents are 
episodic and may wax and wane in frequency. Longitudinal 
course is unknown. Although fire 
setting is a major problem 
in children and adolescents (over 40% of those arrested for arson 
offenses in the United States are younger than 18 years), pyromania in childhood appears to be 
rare. Juvenile fire setting is usually associated with conduct 
disorder, attentiondeficit/
hyperactivity disorder, or an adjustment disorder. 



Sex- and Gender-Related Diagnostic Issues 


While fire setting is associated with antisocial 
behavior in men and women, they differ on some 
of the antisocial 
behaviors that 
accompany fire setting. Whether this holds for pyromania, which 
is a subset of those with fire setting, is unknown. 


Association With Suicidal 
Thoughts or Behavior 


A study of a consecutive sample of male fire setters who had a forensic assessment 
compared 
each case with four age-, sex-, and place of birth matched controls and found that 


539 


fire setting was associated during follow-up with higher rates of suicide and also suicide attempt. 
Whether these differences apply to pyromania is unknown. 


Differential 
Diagnosis 


Other causes 
of 
intentional 
fire 
setting. 
It 
is important 
to rule out 
other causes of fire setting before 
giving the diagnosis of pyromania. Intentional 
fire setting may occur for profit, sabotage, or 
revenge; 
to conceal 
a crime; 
to make a political 
statement 
(e.g., an act 
of terrorism 
or protest); 
or 
to attract 
attention or recognition (e.g., setting a fire in order to discover it 
and save the day). Fire 
setting may also occur as part 
of developmental 
experimentation in childhood (e.g., playing with 
matches, lighters, or fire). 


Other mental 
disorders. 
A separate diagnosis of pyromania is not 
given when fire setting occurs as 
part 
of conduct 
disorder, a manic episode, or antisocial 
personality disorder, or if it 
occurs in 
response to a delusion or a hallucination (e.g., in schizophrenia) or is attributable to the 
physiological 
effects of another medical 
condition (e.g., epilepsy). The diagnosis of pyromania 
should also not 
be given when fire setting results from 
impaired judgment 
associated with major 
neurocognitive disorder, intellectual developmental disorder, or substance intoxication. 


Comorbidity 


There appears to be a high co-occurrence of substance use disorders, gambling disorder, 
depressive and bipolar disorders, and other disruptive, impulse-control, and conduct 
disorders 
with pyromania. 


Kleptomania 


Diagnostic Criteria 
F63.2 


A. 
Recurrent 
failure 
to 
resist 
impulses to 
steal objects that 
are 
not 
needed 
for 
personal use 
or for their monetary value. 
B. 
Increasing 
sense 
of 
tension 
immediately before 
committing 
the 
theft. 
C. 
Pleasure, 
gratification, 
or relief 
at 
the 
time 
of 
committing 
the 
theft. 

D. 
The 
stealing 
is not 
committed 
to 
express anger or vengeance 
and 
is not 
in 
response 
to 
a 
delusion 
or a 
hallucination. 
E. 
The 
stealing 
is not 
better explained 
by conduct 
disorder, 
a 
manic episode, 
or 
antisocial personality disorder. 
Diagnostic Features 


The essential 
feature of kleptomania is the recurrent 
failure to resist 
impulses to steal 
items even 
though the items are not 
needed for personal 
use or for their monetary value (Criterion A). The 
individual 
experiences a rising subjective sense of tension before the theft 
(Criterion B) and feels 
pleasure, gratification, or relief when committing the theft 
(Criterion C). The stealing is not 
committed to express anger or vengeance, is not 
done in response to a delusion or hallucination 
(Criterion D), and is not 
better explained by conduct 
disorder, a manic episode, or antisocial 
personality disorder (Criterion E). The objects are stolen despite the fact 
that 
they are typically of 
little value to the individual, who could have afforded to pay for them 
and often gives them 
away 
or discards them. Occasionally the individual 
may hoard the stolen objects or surreptitiously 
return them. Although individuals with this disorder will 
generally avoid stealing when 
immediate arrest 
is probable (e.g., in full 
view of a police officer), they usually do not 
preplan 
the thefts or fully take 


540 


into account 
the chances of apprehension. The stealing is done without 
assistance from, or 
collaboration with, others. 


Associated Features 


Individuals with kleptomania typically attempt 
to resist 
the impulse to steal, and they are aware 
that 
the act 
is wrong and senseless. The individual 
frequently fears being apprehended and often 
feels depressed or guilty about 
the thefts. Neurotransmitter pathways associated with behavioral 
addictions, including those associated with the serotonin, dopamine, and opioid systems, appear 
to play a role in kleptomania as well. 


Prevalence 


In the United States and Canada, kleptomania occurs in about 
4% 24% of individuals arrested 
for shoplifting. Its prevalence in the U.S. general 
population is very rare, at 
approximately 0.3%  
0.6%. Women outnumber men at a ratio of 3:1. 


Development and Course 


Age at 
onset 
of kleptomania is variable, but 
the disorder often begins in adolescence. However, 
the disorder may begin in childhood, adolescence, or adulthood, and in rare cases in late 
adulthood. There is little systematic information on the course of kleptomania, but 
three typical 
courses have been described: 
sporadic with brief episodes and long periods of remission; 
episodic with protracted periods of stealing and periods of remission; 
and chronic with some 
degree of fluctuation. The disorder may continue for years, despite multiple convictions for 



shoplifting. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
There appears to be a higher rate of alcohol use disorders in first-degree 
relatives of individuals with kleptomania than in the general population. 


Association With Suicidal 
Thoughts or Behavior 


Kleptomania has been associated with an increased risk for suicide attempts. 


Functional 
Consequences of Kleptomania 


The disorder may cause legal, family, career, and personal difficulties. 


Differential 
Diagnosis 


Ordinary 
theft. 
Kleptomania should be distinguished from 
ordinary acts of theft 
or shoplifting. 
Ordinary theft 
(whether planned or impulsive) is deliberate and is motivated by the usefulness of 
the object 
or its monetary worth. Some persons, especially adolescents, may also steal 
on a dare, 
as an act 
of rebellion, or as a rite of passage. The diagnosis is not 
made unless other 
characteristic features of kleptomania are also present. Kleptomania is rare, whereas shoplifting 
is relatively common. 


Malingering. 
In malingering, individuals may simulate the symptoms of kleptomania to avoid 
criminal prosecution. 
Antisocial 
personality 
disorder and 
conduct 
disorder. 
Antisocial 
personality disorder and conduct 


disorder are distinguished from kleptomania by a general pattern of antisocial behavior. 
Manic 
episodes, 
psychotic 
episodes, 
and 
major neurocognitive 
disorder. 
Kleptomania should be 
distinguished from intentional or inadvertent stealing that may occur during a 


541 


manic episode, in response to delusions or hallucinations (e.g., in schizophrenia), or as a result 
of 
a major neurocognitive disorder. 


Comorbidity 


Kleptomania may be associated with compulsive buying as well 
as with depressive and bipolar 
disorders (especially major depressive disorder), anxiety disorders, eating disorders (particularly 
bulimia nervosa), personality disorders, substance use disorders (especially alcohol 
use disorder), 
and other disruptive, impulse-control, and conduct disorders. 


Other Specified 
Disruptive, 
Impulse-Control, 
and 
Conduct 
Disorder 


F91.8 



This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
disruptive, 
impulse-control, 
and 
conduct 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
disruptive, 
impulse-control, 
and 
conduct 
disorders diagnostic class. 
The 
other specified 
disruptive, 
impulse-control, 
and 
conduct 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific disruptive, 
impulse-control, 
and 
conduct 
disorder. 
This is done 
by recording 
 other specified 
disruptive, 
impulse-control, 
and 
conduct 
disorder  followed 
by the 
specific reason 
(e.g., 
 recurrent 
behavioral 
outbursts of 
insufficient 
frequency ). 


Unspecified 
Disruptive, 
Impulse-Control, 
and 
Conduct 
Disorder 


F91.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
disruptive, 
impulse-control, 
and 
conduct 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
disruptive, 
impulse-control, 
and 
conduct 
disorders diagnostic class. 
The 
unspecified 
disruptive, 
impulse-control, 
and 
conduct 
disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific 
disruptive, 
impulse-control, 
and 
conduct 
disorder, 
and 
includes presentations in 
which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room settings). 


542 



543 



Substance-Related and Addictive Disorders 


The substance-related disorders 
encompass 10 separate classes of drugs: 
alcohol; 
caffeine; 
cannabis; 
hallucinogens (with separate categories for phencyclidine [or 
similarly acting arylcyclohexylamines] and other hallucinogens); 
inhalants; 
opioids; 
sedatives, 
hypnotics, or anxiolytics; 
stimulants (amphetamine-type substances, cocaine, and other 
stimulants); 
tobacco; 
and other (or unknown) substances. These 10 classes are not 
fully distinct. 
All 
drugs that 
are taken in excess have in common the ability to directly activate the brain reward 
systems, which are involved in the reinforcement 
of behaviors and establishment 
of memories. 
Instead of achieving reward system 
activation through adaptive behaviors, these substances 
produce such an intense activation of the reward system 
that 
normal 
activities may be neglected. 
The pharmacological 
mechanisms by which each class of drugs produces reward are different, 
but 
the drugs typically activate the system 
and produce feelings of pleasure, often referred to as a 
 high.  Furthermore, studies suggest 
that 
the neurobiological 
roots of substance use disorders for 
some individuals can be seen in their behaviors long before the onset 
of actual 
substance use 
(e.g., lower levels of self-control 
may reflect 
impairments of brain inhibitory mechanisms); 
research also suggests the negative impact 
of substance use itself on brain inhibitory 
mechanisms. 


Note that 
the phrase  drug addiction  is not 
applied as a diagnostic term 
in this classification, 
although it 
is in common usage in many countries to describe severe problems related to 
compulsive and habitual 
use of substances. The more neutral 
term 
substance use disorder 
is used 
to describe the wide range of the disorder, from 
a mild form 
to a severe state of chronically 
relapsing, compulsive pattern of drug taking. Some clinicians will 
choose to use the phrase  drug 
addiction  to describe more severe presentations, but 
that 
wording is omitted from 
the official 
DSM-5 substance use disorder diagnostic terminology because of its uncertain definition and its 
potentially negative connotation. 


In addition to the substance-related disorders, this chapter also includes gambling disorder, 
reflecting evidence that 
gambling behaviors activate reward systems similar to those activated by 
drugs of abuse and that 
produce some behavioral 
symptoms that 
appear comparable to those 
produced by the substance use disorders. Other excessive behavioral 
patterns, such as Internet 
gaming (see  Conditions for Further Study ), have also been described, but 
the research on these 
and other behavioral 
syndromes is less clear. Thus, groups of repetitive behaviors, sometimes 
termed behavioral 
addictions 
(with subcategories such as  sex addiction,   exercise addiction,  
and  shopping addiction ), are not 
included because there is insufficient 
peer-reviewed evidence 
to establish the diagnostic criteria and course descriptions needed to identify these behaviors as 
mental disorders. 


The substance-related disorders are divided into two groups: 
substance use disorders and 
substance-induced disorders. The following conditions may be classified as substance-induced: 
substance intoxication, substance withdrawal, and substance/medication-induced mental 



disorders (diagnostic criteria and text 
are provided in this manual 
for substance/medicationinduced 
psychotic disorders, bipolar and related disorders, depressive disorders, anxiety 
disorders, obsessive-compulsive and related disorders, sleep disorders, sexual 
dysfunctions, 
delirium, and neurocognitive disorders in their respective chapters). The term 


544 


substance/medication-induced mental 
disorder 
refers to symptomatic presentations that 
are 
due to the physiological 
effects of an exogenous substance on the central 
nervous system 
and 
includes typical 
intoxicants (e.g., alcohol, inhalants, cocaine), psychotropic medications (e.g., 
stimulants, sedative-hypnotics), other medications, (e.g., steroids), and environmental 
toxins 
(e.g., organophosphate insecticides). 


The current 
section begins with a general 
discussion of criteria sets for substance use 
disorder, substance intoxication, substance withdrawal, and substance/medication-induced 
mental 
disorders, at 
least 
some of which are applicable across classes of substances. Reflecting 
some unique aspects of the 10 substance classes relevant 
to this chapter, the remainder of the 
chapter is organized by substance class. To facilitate differential 
diagnosis, the diagnostic criteria 
and text 
for the substance/medication-induced mental 
disorders are included with disorders with 
which they share phenomenology (e.g., substance/medication-induced depressive disorder is in 
the chapter  Depressive Disorders ). Note that 
only certain classes of drugs are capable of 
causing particular types of substance-induced disorders. The substance-related diagnostic 
categories associated with specific drug classes are shown in Table 1. 


545 


TABLE 
1 
Diagnoses 
associated 
with 
substance 
class 


Bipolar 
Obsessive-

and 
compulsive 
Psychotic 
related 
Depressive 
Anxiety 
and 
related 
Sleep 
disorders 
disorders 
disorders 
disorders 
disorders 
disorders 
dy 


Alcohol 
I/W 
I/W 
I/W 
I/W 
I/W 
Caffeine 
I 
I/W 
Cannabis 
I 
I 
I/W 
Hallucinogens 
Phencyclidine 
I 
I 
I 
I 
Other 
I* 
I 
I 
I 
hallucinogens 
Inhalants 
I 
I 
I 
Opioids 
I/W 
W 
I/W 
Sedatives, 
I/W 
I/W 
I/W 
W 
I/W 
hypnotics, or 
anxiolytics 
Stimulants** 
I 
I/W 
I/W 
I/W 
I/W 
I/W 
Tobacco 
W 



Other (or 


I/W 
I/W 
I/W 
I/W 
I/W 
I/W 


unknown) 


Note. X = The category is recognized in DSM-5. 
I = The specifier  with onset during intoxication  may be noted for the category. 
W = The specifier  with onset during withdrawal  may be noted for the category. 
I/W = Either 
 with onset 
during intoxication  or 
 with onset 
during withdrawal  may be noted for 
the category. Major = major 
neurocognitive disorder; mild = mild neurocognitive disorder. 
*Also hallucinogen persisting perception disorder (flashbacks). 
**Includes amphetamine-type substances, cocaine, and other or unspecified stimulants. 


Substance-Related Disorders 


Substance Use Disorders 


Diagnostic Features 


The essential 
feature of a substance use disorder is a cluster of cognitive, behavioral, and 
physiological 
symptoms indicating that 
the individual 
continues using the substance despite 
significant 
substance-related problems. As seen in Table 1, the diagnosis of a substance use 
disorder can be applied to all 
10 substance classes included in this chapter except 
caffeine. For 
certain classes, some symptoms are less salient, and in a few instances not 
all 
symptoms apply 
(e.g., withdrawal 
symptoms are not 
specified for phencyclidine use disorder, other hallucinogen 
use disorder, or inhalant 
use disorder). Of note, the consumption of substances, including 
prescribed medications, may depend in part 
on cultural 
background, substance availability, and 
specific local 
drug regulations. Thus, there can be significant 
local 
or cultural 
variation in 
exposure (e.g., countries with cultural 
prohibitions against 
alcohol 
or other substance use may 
have a lower prevalence of substance-related disorders). 


An important 
characteristic of substance use disorders is an underlying change in brain 
circuits that 
may persist 
beyond detoxification, particularly in individuals with severe disorders. 
The behavioral 
effects of these brain changes may be exhibited in the repeated relapses and 
intense drug craving when the individuals are exposed to drug-related stimuli. These persistent 
drug effects may benefit from long-term approaches to treatment. 


Overall, the diagnosis of a substance use disorder is based on a pathological 
pattern of 
behaviors related to use of the substance. To assist 
with organization, the diagnostic items 
making up Criterion A can be considered to fit 
within overall 
groupings of impaired control, 
social impairment, 
risky use, 
and pharmacological 
criteria. 
Impaired control 
over substance use 
is the first 
criteria grouping (Criteria 1 4). The individual 
may take the substance in larger 
amounts or over a longer period than was originally intended (Criterion 1). The individual 
may 
express a persistent desire to cut down or regulate substance use and may report 


546 


multiple unsuccessful 
efforts to decrease or discontinue use (Criterion 2). The individual 
may 
spend a great 
deal 
of time obtaining the substance, using the substance, or recovering from 
its 



effects (Criterion 3). In some instances of more severe substance use disorders, virtually all 
of 
the individual s daily activities revolve around the substance. Craving (Criterion 4) is manifested 
by an intense desire or urge for the drug that 
may occur at 
any time but 
is more likely when in an 
environment 
where the drug previously was obtained or used. Craving has also been shown to 
involve classical 
conditioning and is associated with activation of specific reward structures in 
the brain. Craving might 
be queried by asking if there has ever been a time when there were such 
strong urges to take the drug that 
the individual 
could not 
think of anything else. Current 
craving 
is often used as a treatment outcome measure because it may be a signal of impending relapse. 


Social 
impairment 
is the second grouping of criteria (Criteria 5 7). Recurrent 
substance use 
may result 
in a failure to fulfill 
major role obligations at 
work, school, or home (Criterion 5). The 
individual 
may continue substance use despite having persistent 
or recurrent 
social 
or 
interpersonal 
problems caused or exacerbated by the effects of the substance (Criterion 6). 
Important 
social, occupational, or recreational 
activities may be given up or reduced because of 
substance use (Criterion 7). The individual 
may withdraw from 
family activities and hobbies in 
order to use the substance. 


Risky use of the substance is the third grouping of criteria (Criteria 8 9). This may take the 
form 
of recurrent 
substance use in situations in which it 
is physically hazardous (Criterion 8). 
The individual 
may continue substance use despite knowledge of having a persistent 
or recurrent 
physical 
or psychological 
problem 
that 
is likely to have been caused or exacerbated by the 
substance (Criterion 9). The key issue in evaluating this criterion is not 
the existence of the 
problem, but 
rather the individual s failure to abstain from 
using the substance despite the 
difficulty it is causing. 


Pharmacological 
criteria are the 
final 
grouping (Criteria 10 and 11). Tolerance (Criterion 10) 
is signaled by requiring a markedly increased dose of the substance to achieve the desired effect 
or a markedly reduced effect 
when the usual 
dose is consumed. The degree to which tolerance 
develops varies greatly across different 
individuals as well 
as across substances and may involve 
a variety of central 
nervous system 
effects. For example, tolerance to respiratory depression and 
tolerance to sedating and motor coordination may develop at 
different 
rates, depending on the 
substance. Tolerance may be difficult 
to determine by history alone, and laboratory tests may be 
helpful 
(e.g., high blood levels of the substance coupled with little evidence of intoxication 
suggest 
that 
tolerance is likely). Tolerance must 
also be distinguished from 
individual 
variability 
in the initial 
sensitivity to the effects of particular substances. For example, some first-time 
alcohol 
drinkers show very little evidence of intoxication with three or four drinks, whereas 
others of similar weight and drinking histories have slurred speech and incoordination. 


Withdrawal 
(Criterion 11) is a syndrome that 
occurs when blood or tissue concentrations of a 
substance decline in an individual 
who had maintained prolonged, heavy use of the substance. 
After developing withdrawal 
symptoms, the individual 
is likely to consume the substance to 
relieve the symptoms. Withdrawal 
symptoms vary greatly across the classes of substances, and 
separate criteria sets for withdrawal 
are provided for the drug classes. Marked and generally 
easily measured physiological 
signs of withdrawal 
are common with alcohol, opioids, and 
sedatives, hypnotics, and anxiolytics. Withdrawal 
signs and symptoms with stimulants 
(amphetamine-type substances, cocaine, other or unspecified stimulants), as well 
as tobacco and 
cannabis, are often present 
but 
may be less apparent. Significant 
withdrawal 
has not 
been 
documented in humans after repeated use of phencyclidine, other hallucinogens, and inhalants; 
therefore, this criterion is not 
included for these substances. Neither tolerance nor withdrawal 
is 



necessary for a diagnosis of a substance use disorder. However, for most 
classes of substances, a 
past history of withdrawal is associated with a 


547 


more severe clinical 
course (i.e., an earlier onset 
of a substance use disorder, higher levels of 
substance intake, and a greater number of substance-related problems). 


Symptoms of tolerance and withdrawal 
occurring during appropriate use of prescribed 
medications given as part 
of medical 
treatment 
(e.g., opioid analgesics, sedatives, stimulants) are 
specifically not 
counted when diagnosing a substance use disorder. The appearance of normal, 
expected pharmacological 
tolerance and withdrawal 
during the course of medical 
treatment 
has 
been known to lead to an erroneous diagnosis of  addiction  even when these were the only 
symptoms present. Individuals whose only 
symptoms are those that 
occur as a result 
of medical 
treatment 
(i.e., tolerance and withdrawal 
as part 
of medical 
care when the medications are taken 
as prescribed) should not 
receive a diagnosis solely on the basis of these symptoms. However, 
prescription medications can be used inappropriately, and a substance use disorder can be 
correctly diagnosed when there are other symptoms of compulsive, drug-seeking behavior. 


Severity and Specifiers 


Substance use disorders occur in a broad range of severity, from 
mild to severe, with severity 
based on the number of symptom 
criteria endorsed. As a general 
estimate of severity, a mild 
substance use disorder is suggested by the presence of two to three symptoms, moderate 
by four 
to five symptoms, and severe 
by six or more symptoms. Changing severity across time is also 
reflected by reductions or increases in the frequency and/or dose of substance use, as assessed by 
the individual s own report, report 
of knowledgeable others, clinician s observations, and 
biological 
testing. The following course specifiers and descriptive features specifiers are also 
available for substance use disorders: 
 in early remission,   in sustained remission,   on 
maintenance therapy,  and  in a controlled environment.  Definitions of each are provided 
within respective criteria sets. 


Recording Procedures 


The clinician should use the code that 
applies to the substance class but 
record the name of the 
specific substance. 
For example, the clinician should record F13.20 moderate alprazolam 
use 
disorder (rather than moderate sedative, hypnotic, or anxiolytic use disorder) or F15.10 mild 
methamphetamine use disorder (rather than mild amphetamine-type substance use disorder). For 
substances that 
do not 
fit 
into any of the classes (e.g., anabolic steroids), the ICD-10-CM code 
for other (or unknown) substance use disorder should be used and the specific substance 
indicated (e.g., F19.10 mild anabolic steroid use disorder). If the substance taken by the 
individual 
is unknown, the same ICD-10-CM code (i.e., for  other [or unknown] substance use 
disorder ) should be used (e.g., F19.20 severe unknown substance use disorder). If criteria are 
met 
for more than one substance use disorder, each should be diagnosed (e.g., F11.20 severe 
heroin use disorder; F14.20 moderate cocaine use disorder). 


The appropriate ICD-10-CM code for a substance use disorder depends on whether there is a 



comorbid substance-induced disorder (including substance intoxication and substance 
withdrawal). In the first 
example in the paragraph above, the diagnostic code for moderate 
alprazolam 
use disorder, F13.20, reflects the absence of a comorbid alprazolam-induced mental 
disorder. Because ICD-10-CM codes for substance-induced disorders indicate both the presence 
(or absence) and the severity of the substance use disorder, ICD-10-CM codes for substance use 
disorders can be used only in the absence of a substance-induced disorder. See the individual 
substance-specific sections for additional coding information. 


548 


Substance-Induced 
Disorders 


The overall 
category of substance-induced disorders includes substance intoxication, substance 
withdrawal, and substance/medication-induced mental 
disorders (e.g., substance-induced 
psychotic disorder, substance-induced depressive disorder). While substance intoxication and 
substance withdrawal 
are recognized as mental 
disorders, for purposes of clarity of reference in 
discussions across this chapter, the term 
substance/medication-induced mental 
disorder 
(e.g., 
alcohol-induced depressive disorder, methamphetamine-induced anxiety disorder) is used to 
distinguish these disorders from substance intoxication and substance withdrawal. 


Substance Intoxication and Substance Withdrawal 


Criteria for the substance-specific intoxication syndromes are included within the substance-
specific sections of this chapter. The essential 
feature is the development 
of a reversible 
substance-specific syndrome due to the recent 
ingestion of a substance (Criterion A). The 
clinically significant 
problematic behavioral 
or psychological 
changes associated with 
intoxication (e.g., belligerence, mood lability, impaired judgment) are attributable to the 
physiological 
effects of the substance on the central 
nervous system 
(CNS) and develop during 
or shortly after use of the substance (Criterion B) and are accompanied by substance-specific 
signs and symptoms (Criterion C). The symptoms are not 
attributable to another medical 
condition and are not 
better explained by another mental 
disorder (Criterion D). Substance 
intoxication is common among individuals with a substance use disorder but 
also occurs 
frequently in persons who use substances but 
do not 
have a substance use disorder. This category 
does not apply to tobacco. 


The most 
common changes in substance intoxication involve disturbances of perception, 
wakefulness, attention, thinking, judgment, psychomotor behavior, and interpersonal 
behavior. 
Short-term, or  acute,  substance intoxications may have different 
signs and symptoms from 
sustained, or  chronic,  substance intoxications. For example, moderate cocaine doses may 
initially produce gregariousness, but 
social 
withdrawal 
may develop if such doses are frequently 
repeated over days or weeks. 


When used in the physiological 
sense, the term 
intoxication 
is broader than the diagnosis of 
substance intoxication as defined in this manual. Many substances may produce physiological 
or 
psychological 
changes that 
are not 
necessarily problematic. For example, an individual 
with 
tachycardia from 
substance use is experiencing a physiological 
effect 
from 
the substance, but 
if 



this is the only symptom 
in the absence of problematic behavior, the diagnosis of substance 
intoxication would not 
apply. Intoxication may sometimes persist 
beyond the time when the 
substance is detectable in the body. This may be attributable to enduring CNS 
effects, from 
which the recovery takes longer than the time for elimination of the substance. These longer-term 
effects of intoxication must 
be distinguished from 
withdrawal 
(i.e., symptoms initiated by a 
decline in blood or tissue concentrations of a substance). 


Criteria for substance withdrawal 
are also included within the substance-specific sections of 
this chapter. The essential 
feature is the development 
of a substance-specific problematic 
behavioral 
change, with physiological 
and cognitive concomitants, that 
is due to the cessation of, 
or reduction in, heavy and prolonged substance use (Criterion A). The substance-specific 
syndrome (Criterion B) causes clinically significant 
distress or impairment 
in social, 
occupational, or other important 
areas of functioning (Criterion C). The symptoms are not 
due to 
another medical 
condition and are not 
better explained by another mental 
disorder (Criterion D). 
Withdrawal 
is usually, but 
not 
always, associated with a substance use disorder. Also, it 
is 
important 
to emphasize that 
symptoms of withdrawal 
occurring during appropriate use of 
medications given as part of medical treatment with 


549 


prescribed medications (e.g., opioid analgesics, sedatives, stimulants) are specifically not 
counted when diagnosing a substance use disorder. Most 
individuals with withdrawal 
have an 
urge to readminister the substance to reduce the symptoms. 


Route of Administration and Speed of Substance Effects 


Routes of administration that 
produce more rapid and efficient 
absorption into the bloodstream 
(e.g., intravenous, smoking, intranasal 
 snorting ) tend to result 
in a more intense intoxication 
and an increased likelihood of an escalating pattern of substance use leading to withdrawal. 
Similarly, rapidly acting substances are more likely than slower-acting substances to produce 
immediate intoxication. 


Duration of Effects 


Within the same drug category, relatively short-acting substances tend to have a higher potential 
for the development 
of withdrawal 
than do those with a longer duration of action. However, 
longer-acting substances tend to have longer duration of withdrawal 
symptoms. The half-life of 
the substance parallels aspects of withdrawal: 
the longer the duration of action, the longer the 
time between cessation and the onset 
of withdrawal 
symptoms and the longer the withdrawal 
duration. In general, the longer the acute withdrawal 
period, the less intense the syndrome tends 
to be. 


Use of Multiple Substances 


Substance intoxication and withdrawal 
often involve several 
substances used simultaneously or 
sequentially. In these cases, each diagnosis should be recorded separately. 


Associated Laboratory Findings 



Laboratory analyses of blood and urine samples can help determine recent 
use and the specific 
substances involved. However, a positive laboratory test 
result 
does not 
by itself indicate that 
the 
individual 
has a pattern of substance use that 
meets criteria for a substance-induced or substance 
use disorder, and a negative test result does not by itself rule out a diagnosis. 


Laboratory tests can be useful 
in identifying withdrawal. If the individual 
presents with 
withdrawal 
from 
an unknown substance, laboratory tests may help identify the substance and 
may also be helpful 
in differentiating withdrawal 
from 
other mental 
disorders. In addition, 
normal 
functioning in the presence of high blood levels of a substance suggests considerable 
tolerance. 


Development and Course 


Individuals ages 18 24 years have relatively high prevalence rates for the use of virtually every 
substance. Intoxication is usually the initial 
substance-related disorder and often begins in the 
teens. Withdrawal 
can occur at 
any age as long as the relevant 
drug has been taken in sufficient 
doses over an extended period of time. 


Recording Procedures for Substance Intoxication and Substance 
Withdrawal 


The clinician should use the code that 
applies to the class of substances but 
record the name of 
the specific substance. 
For example, the clinician should record F13.230 secobarbital 
withdrawal 
(rather than sedative, hypnotic, or anxiolytic withdrawal) or F15.120 methamphetamine 
intoxication (rather than amphetamine-type substance intoxication). Note that 


550 


the appropriate ICD-10-CM diagnostic codes for substance intoxication and substance 
withdrawal 
depend on whether there is a comorbid substance use disorder. In this case, the 
F15.120 code for methamphetamine intoxication indicates the presence of a comorbid mild 
methamphetamine use disorder. If there had been no comorbid methamphetamine use disorder 
(and no perceptual 
disturbances), the diagnostic code would have been F15.920. See the coding 
note for the substance-specific intoxication and withdrawal 
syndromes for the actual 
coding 
options. 


For substances that 
do not 
fit 
into any of the classes (e.g., anabolic steroids), the ICD-10-CM 
code for other (or unknown) substance intoxication or other (or unknown) substance withdrawal 
should be used and the specific substance indicated (e.g., F19.920 anabolic steroid intoxication). 
If the substance taken by the individual 
is unknown, the same code (i.e., for the class  other [or 
unknown] substance ) should be used (e.g., F19.920 unknown substance intoxication). If there 
are symptoms or problems associated with a particular substance but 
criteria are not 
met 
for any 
of the substance-specific disorders, the unspecified category can be used (e.g., F12.99 
unspecified cannabis-related disorder). 


As noted above, the substance-related codes in ICD-10-CM combine the substance use 
disorder aspect 
of the clinical 
picture and the substance-induced aspect 
into a single combined 
code. Thus, if both heroin withdrawal 
and moderate heroin use disorder are present, the single 
code F11.23 for heroin withdrawal 
is given to cover both presentations. See the individual 



substance-specific sections for additional coding information. 


Substance/Medication-Induced Mental Disorders 


The substance/medication-induced mental 
disorders are potentially severe, usually temporary, 
but 
sometimes persisting CNS 
syndromes that 
develop in the context 
of the effects of substances 
of abuse, medications, and some toxins. They are distinguished from 
the substance use disorders, 
in which a cluster of cognitive, behavioral, and physiological 
symptoms contribute to the 
continued use of a substance despite significant 
substance-related problems. The 
substance/medication-induced mental 
disorders may be induced by any of the 10 classes of 
substances that 
produce substance use disorders, or by a great 
variety of other medications used 
in medical 
treatment. Each substance/medication-induced mental 
disorder is described in the 
relevant 
chapter (e.g., substance/medication-induced depressive disorder is located in 
 Depressive Disorders ), and therefore, only a brief description is offered here. All 
substance/medication-induced disorders share common characteristics. It 
is important 
to 
recognize these common features to aid in the detection of these disorders. These features are 
described as follows: 


A. A clinically significant 
presentation of symptoms characteristic of disorders in the relevant 
diagnostic class predominates in the clinical picture. 
B. There is evidence from 
the history, physical 
examination, or laboratory findings of both of 
the following: 
1. The symptoms in Criterion A developed during or soon after substance intoxication, 
substance withdrawal, or exposure to or withdrawal from a medication; and 
2. The involved substance/medication is capable of producing the symptoms in Criterion A. 
C. The disturbance is not 
better explained by an independent 
mental 
disorder (i.e., one that 
is 
not 
substance- or medication-induced). Such evidence of an independent 
mental 
disorder 
could include the following: 
1. The disturbance preceded the onset of severe intoxication or withdrawal or exposure to the 
medication; or 
2. The disturbance persisted for a substantial 
period of time (e.g., at 
least 
1 month) after the 
cessation of acute withdrawal or severe intoxication or taking the 
551 


medication. This criterion does not 
apply to substance-induced neurocognitive disorders 
or hallucinogen persisting perception disorder, which persist 
beyond the cessation of acute 
intoxication or withdrawal. 


D. The disturbance does not occur exclusively during the course of a delirium. 
E. The disturbance causes clinically significant 
distress or impairment 
in social, occupational, 
or other important areas of functioning. 
Diagnostic and Associated Features 



Some generalizations can be made regarding the categories of substances capable of producing 
clinically relevant 
substance-induced mental 
disorders. In general, the more sedating drugs 
(sedative, hypnotics, or anxiolytics, and alcohol) can produce prominent 
and clinically 
significant 
depressive disorders during intoxication, while anxiety conditions are likely to be 
observed during withdrawal 
syndromes from 
these substances. Also, during intoxication, the 
more stimulating substances (e.g., amphetamines and cocaine) are likely to be associated with 
substance-induced psychotic disorders and substance-induced anxiety disorders, and with 
substance-induced major depressive episodes observed during withdrawal. Both the more 
sedating and the more stimulating drugs are likely to produce significant 
but 
temporary sleep and 
sexual 
disturbances. An overview of the relationship between specific categories of substances 
and specific psychiatric syndromes is presented in Table 1. 


The medication-induced conditions include what 
are often idiosyncratic CNS 
reactions or 
relatively extreme examples of side effects for a wide range of medications taken for a variety of 
medical 
concerns. These include neurocognitive complications of anesthetics, antihistamines, 
antihypertensives, and a variety of other medications and toxins (e.g., organophosphates, 
insecticides, carbon monoxide), as described in the chapter on neurocognitive disorders. 
Psychotic syndromes may be temporarily experienced in the context 
of anticholinergic, 
cardiovascular, and steroid drugs, as well 
as during use of stimulant-like and depressant-like 
prescription or over-the-counter drugs. Temporary but severe mood disturbances can be observed 
with a wide range of medications, including steroids, antihypertensives, disulfiram, and any 
prescription or over-the-counter depressant 
or stimulant-like substances. A similar range of 
medications can be associated with temporary anxiety syndromes, sexual 
dysfunctions, and 
conditions of disturbed sleep. 


In general, to be considered a substance/medication-induced mental 
disorder, there must 
be 
evidence that 
the symptoms being observed are not 
likely to be better explained by an 
independent 
mental 
disorder. The latter is more likely to be the case if the symptoms were 
present 
before the severe intoxication or withdrawal 
or medication administration, or, with the 
exception of several 
substance-induced persisting disorders listed in 1, continued more than 1 
month after cessation of acute withdrawal, severe intoxication, or use of the medications. When 
symptoms are only observed during a substance-induced delirium 
(e.g., alcohol 
withdrawal 
delirium), only the delirium 
should be diagnosed, and other psychiatric symptoms occurring 
during the delirium 
should not 
also be diagnosed separately, as many of these symptoms (e.g., 
disturbances in mood, anxiety, reality testing) are commonly seen during agitated, confused 
states. The features associated with each relevant 
major mental 
disorder are similar whether 
observed with independent 
or substance/medication-induced mental 
disorders. However, 
individuals with substance/medication-induced mental 
disorders are likely to also demonstrate 
the associated features seen with the specific category of substance or medication, as listed in 
other subsections of this chapter. 


Development and Course 


Substance-induced mental 
disorders develop in the context 
of intoxication with or withdrawal 
from 
substances of abuse, whereas medication-induced mental 
disorders can be seen with 
prescribed or over-the-counter medications that are taken at the suggested doses. 



552 


Both conditions are usually temporary and likely to disappear within 1 month or so of cessation 
of acute withdrawal, severe intoxication, or use of the medication. Exceptions to these 
generalizations occur for certain long-duration substance-induced disorders: substance-associated 
neurocognitive disorders that 
relate to conditions such as alcohol-induced neurocognitive 
disorder, inhalant-induced neurocognitive disorder, and sedative-, hypnotic-, or anxiolyticinduced 
neurocognitive disorder; 
and hallucinogen persisting perception disorder ( flashbacks ; 
see the section  Hallucinogen-Related Disorders  later in this chapter). However, most 
substance/medication-induced mental 
disorders, regardless of the severity of the symptoms, are 
likely to improve relatively quickly with abstinence and unlikely to remain clinically relevant 
for 
more than 1 month after complete cessation of use. 


As is true of many consequences of heavy substance use, some individuals are more and 
others less prone toward developing specific substance-induced disorders. Similar types of 
predispositions may make some 
individuals more likely to develop psychiatric side effects of 
some types of medications, but 
not 
others. However, it 
is unclear whether individuals with 
family histories or personal 
prior histories of independent 
psychiatric syndromes are more likely 
to develop the induced syndrome once the consideration is made as to whether the quantity and 
frequency of the substance were sufficient 
to lead to the development 
of a substance-induced 
syndrome. 


There are indications that 
the intake of substances of abuse or some medications with 
psychiatric side effects in the context 
of a preexisting mental 
disorder is likely to result 
in an 
intensification of the symptoms of the preexisting mental 
disorder. The risk for 
substance/medication-induced mental 
disorders is likely to increase with both the quantity and 
the frequency of consumption of the relevant substance. 


The symptom 
profiles for the substance/medication-induced mental 
disorders resemble 
independent 
mental 
disorders. While the symptoms of substance/medication-induced mental 
disorders can be identical 
to those of independent 
mental 
disorders (e.g., delusions, 
hallucinations, psychoses, major depressive episodes, anxiety syndromes), and although they can 
have the same severe consequences (e.g., suicide), most 
induced mental 
disorders are likely to 
improve in a matter of days to weeks of abstinence. 


The substance/medication-induced mental 
disorders are an important 
part 
of the differential 
diagnoses for the independent 
psychiatric conditions. The importance of recognizing an induced 
mental 
disorder is similar to the relevance of identifying the possible role of some medical 
conditions and medication reactions before diagnosing an independent 
mental 
disorder. 
Symptoms of substance- and medication-induced mental 
disorders may be identical 
cross-
sectionally to those of independent 
mental 
disorders but 
have different 
treatments and prognoses 
from the independent condition. 


Functional 
Consequences of Substance/Medication-Induced Mental 
Disorders 


The same consequences related to the relevant 
independent 
mental 
disorder (e.g., suicide 
attempts) are likely to apply to the substance/medication-induced mental 
disorders, but 
these are 
likely to disappear within 1 month after abstinence. Similarly, the same functional 
consequences 



associated with the relevant 
substance use disorder are likely to be seen for the substance-
induced mental disorders. 


Recording Procedures for Substance/Medication-Induced Mental 
Disorders 


Diagnostic criteria, coding notes, and recording procedures for the specific 
substance/medication-induced mental 
disorders are provided in chapters of the manual 
corresponding with disorders of shared phenomenology (see the substance/medication-induced 


553 


mental 
disorders in these chapters: 
 Schizophrenia Spectrum 
and Other Psychotic Disorders,  
 Bipolar and Related Disorders,   Depressive Disorders,   Anxiety Disorders,   Obsessive-
Compulsive and Related Disorders,   Sleep-Wake Disorders,   Sexual 
Dysfunctions,  and 
 Neurocognitive Disorders ). When recording a substance/medication-induced mental 
disorder 
that 
is comorbid with a substance use disorder, only a single diagnosis is given that 
reflects both 
the type of substance and the type of mental 
disorder induced by the substance, as well 
as the 
severity of the comorbid substance use disorder (e.g., cocaine-induced psychotic disorder with 
severe cocaine use disorder). For a substance-induced mental 
disorder occurring in the absence 
of comorbid substance use disorder (e.g., when the disorder is induced by one-time use of a 
substance or medication), only the substance/medication-induced mental 
disorder is recorded 
(e.g., corticosteroid-induced depressive disorder). Additional 
information needed to record the 
diagnostic name of the substance/medication-induced mental 
disorder is provided in the section 
 Recording Procedures  for each substance/medication-induced mental 
disorder in its respective 
chapter. 


Alcohol-Related Disorders 


Alcohol Use 
Disorder 
Alcohol Intoxication 
Alcohol Withdrawal 
Alcohol-Induced 
Mental Disorders 
Unspecified 
Alcohol-Related 
Disorder 


Alcohol 
Use Disorder 


Diagnostic Criteria 
A. 
A 
problematic pattern 
of 
alcohol use 
leading 
to 
clinically significant 
impairment 
or 



distress, 
as manifested 
by at 
least 
two 
of 
the 
following, 
occurring 
within 
a 
12month 
period: 


1. 
Alcohol is often 
taken 
in 
larger amounts or over a 
longer period 
than 
was 
intended. 
2. 
There 
is a 
persistent 
desire 
or unsuccessful efforts to 
cut 
down 
or control 
alcohol use. 
3. 
A 
great 
deal of 
time 
is spent 
in 
activities necessary to 
obtain 
alcohol, 
use 
alcohol, 
or recover from its effects. 
4. 
Craving, 
or a 
strong 
desire 
or urge 
to 
use 
alcohol. 
5. 
Recurrent 
alcohol use 
resulting 
in 
a 
failure 
to 
fulfill major role 
obligations at 
work, 
school, 
or home. 
6. 
Continued 
alcohol use 
despite 
having 
persistent 
or recurrent 
social or 
interpersonal problems caused 
or exacerbated 
by the 
effects of 
alcohol. 
7. 
Important 
social, 
occupational, 
or recreational activities are 
given 
up 
or 
reduced 
because 
of 
alcohol use. 
8. 
Recurrent 
alcohol use 
in 
situations in 
which 
it 
is physically hazardous. 
554 


9. 
Alcohol use 
is continued 
despite 
knowledge 
of 
having 
a 
persistent 
or 
recurrent 
physical or psychological problem that 
is likely to 
have 
been 
caused 
or exacerbated 
by alcohol. 
10. 
Tolerance, 
as defined 
by either of 
the 
following: 
a. 
A 
need 
for markedly increased 
amounts of 
alcohol to 
achieve 
intoxication 
or desired 
effect. 
b. 
A 
markedly diminished 
effect 
with 
continued 
use 
of 
the 
same 
amount 
of 
alcohol. 
11. 
Withdrawal, 
as manifested 
by either of 
the 
following: 
a. 
The 
characteristic withdrawal syndrome 
for alcohol (refer to 
Criteria 
A 
and 
B 
of 
the 
criteria 
set 
for alcohol withdrawal). 
b. 
Alcohol (or a 
closely related 
substance, 
such 
as a 
benzodiazepine) is 
taken 
to 
relieve 
or avoid 
withdrawal symptoms. 
Specify 
if: 
In 
early 
remission: 
After full criteria 
for alcohol use 
disorder were 
previously 
met, 
none 
of 
the 
criteria 
for alcohol use 
disorder have 
been 
met 
for at 
least 
3 
months but 
for less than 
12 
months (with 
the 
exception 
that 
Criterion 
A4, 
 Craving, 
or a 
strong 
desire 
or urge 
to 
use 
alcohol,  may be 
met). 


In 
sustained 
remission: 
After full criteria 
for alcohol use 
disorder were 
previously met, 
none 
of 
the 
criteria 
for alcohol use 
disorder have 
been 
met 
at 
any time 
during 
a 
period 
of 
12 
months or longer (with 
the 
exception 
that 
Criterion 
A4, 
 Craving, 
or a 
strong 
desire 
or urge 
to 
use 
alcohol,  may be 
met). 



Specify 
if: 
In 
a 
controlled 
environment: 
This additional specifier is used 
if 
the 
individual is 
in 
an 
environment 
where 
access to 
alcohol is restricted. 
Code 
based 
on 
current severity/remission: 
If 
an 
alcohol intoxication, 
alcohol 
withdrawal, 
or another alcohol-induced 
mental disorder is also 
present, 
do 
not 
use 
the 
codes below for alcohol use 
disorder. 
Instead, 
the 
comorbid 
alcohol use 
disorder 
is indicated 
in 
the 
4th 
character of 
the 
alcohol-induced 
disorder code 
(see 
the 
coding 
note 
for alcohol intoxication, 
alcohol withdrawal, 
or a 
specific alcohol-induced 
mental 
disorder). 
For example, 
if 
there 
is comorbid 
alcohol intoxication 
and 
alcohol use 
disorder, 
only the 
alcohol intoxication 
code 
is given, 
with 
the 
4th 
character indicating 
whether the 
comorbid 
alcohol use 
disorder is mild, 
moderate, 
or severe: 
F10.129 
for 


mild 
alcohol use 
disorder with 
alcohol intoxication 
or F10.229 
for a 
moderate 
or 
severe 
alcohol use 
disorder with 
alcohol intoxication. 
Specify 
current 
severity/remission: 


F10.10 
Mild: 
Presence 
of 
2 3 
symptoms. 
F10.11 
Mild, 
In 
early 
remission 
F10.11 
Mild, 
In 
sustained 
remission 
F10.20 
Moderate: 
Presence 
of 
4 5 
symptoms. 
F10.21 
Moderate, 
In 
early 
remission 
F10.21 
Moderate, 
In 
sustained 
remission 
F10.20 
Severe: 
Presence 
of 
6 
or more 
symptoms. 
F10.21 
Severe, 
In 
early 
remission 
F10.21 
Severe, 
In 
sustained 
remission 


555 


Specifiers 


 In a controlled environment  applies as a further specifier of remission if the individual 
is both 
in remission and in a controlled environment 
(i.e., in early remission in a controlled environment 
or in sustained remission in a controlled environment). Examples of these environments are 
closely supervised and substance-free jails, therapeutic communities, and locked hospital units. 


Severity of the disorder is based on the number of diagnostic criteria endorsed. For a given 
individual, changes in severity of alcohol 
use disorder across time are also reflected by 
reductions in the frequency (e.g., days of use per month) or dose (e.g., number of standard drinks 
consumed per day) of alcohol 
used, as assessed by the individual s self-report, report 
of 
knowledgeable others, clinician observations, and, when practical, biological 
testing (e.g., 
elevations in blood tests as described in the section  Diagnostic Markers  for this disorder). 


Diagnostic Features 


Alcohol 
use disorder is defined by a cluster of behavioral 
and physical 
symptoms, such as 
withdrawal, tolerance, and craving. Alcohol 
withdrawal 
is characterized by withdrawal 



symptoms that 
develop approximately 4 12 hours after the reduction of intake following 
prolonged, heavy alcohol 
ingestion. Because withdrawal 
from 
alcohol 
can be unpleasant 
and 
intense, individuals may continue to consume alcohol 
despite adverse consequences, often to 
avoid or to relieve withdrawal 
symptoms. Some withdrawal 
symptoms (e.g., sleep problems) can 
persist 
at 
lower intensities for months and can contribute to relapse. Once a pattern of repetitive 
and intense use develops, individuals with alcohol 
use disorder may devote substantial 
periods of 
their time to obtaining and consuming alcoholic beverages. 


Craving for alcohol 
is indicated by a strong desire to drink that 
makes it 
difficult 
to think of 
anything else and that 
often results in the onset 
of drinking. School 
and job performance may 
also suffer either from 
the aftereffects of drinking or from 
actual 
intoxication at 
school 
or on the 
job; 
child care or household responsibilities may be neglected; 
and alcohol-related absences may 
occur from 
school 
or work. The individual 
may use alcohol 
in physically hazardous 
circumstances (e.g., driving an automobile, swimming, operating machinery while intoxicated). 
Finally, individuals with an alcohol 
use disorder may continue to consume alcohol 
despite the 
knowledge that 
continued consumption poses significant 
physical 
(e.g., blackouts, liver disease), 
psychological 
(e.g., depression), social, or interpersonal 
problems (e.g., violent 
arguments with 
spouse while intoxicated, child abuse). 


Associated Features 


Alcohol 
use disorder is often associated with problems similar to those associated with other 
substances (e.g., cannabis; 
cocaine; 
heroin; 
amphetamines; 
sedatives, hypnotics, or anxiolytics). 
Alcohol 
may be used to alleviate the unwanted effects of these other substances or to substitute 
for them 
when they are not 
available. Symptoms of conduct 
problems, depression, anxiety, and 
insomnia frequently accompany heavy drinking and sometimes precede it. 


Repeated intake of high doses of alcohol 
can affect 
nearly every organ system, especially the 
gastrointestinal 
tract, cardiovascular system, and the central 
and peripheral 
nervous systems. 
Gastrointestinal 
effects include gastritis, stomach or duodenal 
ulcers, and, in about 
15% of 
individuals who use alcohol 
heavily, liver cirrhosis and/or pancreatitis. There is also an increased 
rate of cancer of the esophagus, stomach, and other parts of the gastrointestinal 
tract. One of the 
most 
commonly associated conditions is low-grade hypertension. Cardiomyopathy and other 
myopathies are less common but 
occur at 
an increased rate among those who drink very heavily. 
These factors, along with marked 


556 


increases in levels of triglycerides and low-density lipoprotein cholesterol, contribute to an 
elevated risk of heart 
disease. Peripheral 
neuropathy may be evidenced by muscular weakness, 
paresthesias, and decreased peripheral 
sensation. More persistent 
central 
nervous system 
effects 
include cognitive deficits, such as severe memory impairment 
and degenerative changes in the 
cerebellum. These effects are related to the direct 
effects of alcohol, trauma, or vitamin 
deficiencies (particularly of the B 
vitamins, including thiamine). One devastating central 
nervous 
system 
effect 
is the relatively rare alcohol-induced persisting amnestic disorder, or Wernicke-
Korsakoff syndrome, in which the ability to encode new memory is severely impaired. This 
condition would now be described within the chapter  Neurocognitive Disorders  and would be 



termed a substance/medication-induced neurocognitive disorder. 


Alcohol 
use disorder is an important 
contributor to suicide risk during severe intoxication 
and in the context 
of a temporary alcohol-induced depressive or bipolar disorder. There is an 
increased rate of suicidal behavior as well as of suicide among individuals with the disorder. 


Prevalence 


Alcohol 
use disorder is common. In the United States, lifetime prevalence rates of DSM-5 
alcohol 
use disorder among adults were estimated to be 29.1% overall 
with severity specified as 
follows: 
8.6% mild, 6.6% moderate, and 13.9% severe. Among Australian adults, the estimated 
lifetime prevalence of DSM-5 alcohol use disorder was 31.0%. 


Rates of disorder vary by gender and age. In the United States, rates were greater among men 
(36.0% lifetime prevalence) than among women (22.7%). Twelve-month prevalence of DSM-IV 
alcohol 
use disorders in the United States was 4.6% among individuals ages 12 17 years, 16.2% 
among individuals ages 18 29 years, and 1.5% among individuals 65 years and older. 


Twelve-month prevalence of alcohol 
use disorders varies across U.S. ethnoracial 
groups as 
well. For individuals ages 12 17 years, prevalence of DSM-IV alcohol 
use disorders was 
greatest 
among Native Americans (2.8%) and non-Latinx Whites (2.2%), relative to Asian 
Americans (1.6%), individuals reporting two or more racialized backgrounds (1.6%), Hispanics 
(1.5%), and African Americans (0.8%). Among adults, data from 
a large U.S. population-based 
study indicated that 
the 12-month prevalence of DSM-5 alcohol 
use disorder was 14.4% in 
African Americans, 14.0% in non-Hispanic Whites, 13.6% in Hispanics, and 10.6% in Asian 
Americans and Pacific Islanders. Data from 
a large community-based survey of Native 
Americans from 
Southwestern and Northern Plains tribal 
nations showed that 
the 12-month 
prevalence of DSM-IV alcohol 
abuse and dependence ranged from 
4.1% to 9.8%. There is 
extensive diversity in the rates and patterns of alcohol 
abuse and dependence across the more 
than 570 American Indian and Alaska Native communities in the United States, as well 
as high 
rates of abstinence from 
alcohol 
use in some of these communities. Historical 
experiences of 
dispossession and subjugation and ongoing discrimination have been associated with increased 
risk of symptom 
onset. Given the diversity of tribal 
communities, prevalence estimates for 
alcohol use disorder among Native Americans should be interpreted with caution. 


Development and Course 


The first 
episode of alcohol 
intoxication is likely to occur during the mid-teens. Alcohol-related 
problems that 
do not 
meet 
full 
criteria for a use disorder or isolated problems may occur before 
age 20 years, but 
the age at 
onset 
of an alcohol 
use disorder with two or more of the criteria 
clustered together peaks in the late teens or early to mid 20s. The large majority of individuals 
who develop alcohol-related disorders do so by their late 30s. The first 
evidence of withdrawal 
is 
not 
likely to appear until 
after many other aspects of an alcohol 
use disorder have developed. An 
earlier onset 
of alcohol 
use disorder is observed in adolescents with preexisting conduct 
problems and those with an earlier onset of intoxication. 


557 


Alcohol 
use disorder has a variable course that 
is characterized by periods of remission and 



relapse. A decision to stop drinking, often in response to a crisis, is likely to be followed by a 
period of weeks or more of abstinence, which is often followed by limited periods of controlled 
or nonproblematic drinking. However, once alcohol 
intake resumes, it 
is highly likely that 
consumption will rapidly escalate and that severe problems will once again develop. 


Alcohol 
use disorder is often erroneously perceived as an intractable condition, perhaps 
based on the fact 
that 
individuals who present 
for treatment 
typically have a history of many 
years of severe alcohol-related problems. However, these most 
severe cases represent 
only a 
minority of individuals with this disorder, and the typical 
individual 
with the disorder has a much 
more promising prognosis. 


Among adolescents, conduct 
disorder and repeated antisocial 
behavior often co-occur with 
alcohol- and with other substance-related disorders. While most 
individuals with alcohol 
use 
disorder develop the condition before age 40 years, perhaps 10% have later onset, as suggested 
by a prospective study in California. Age-related physical 
changes in older individuals result 
in 
increased brain susceptibility to the depressant 
effects of alcohol; 
decreased rates of liver 
metabolism 
of a variety of substances, including alcohol; 
and decreased percentages of body 
water. These changes can cause older people to develop more severe intoxication and subsequent 
problems at 
lower levels of consumption. Alcohol-related problems in older people are also 
especially likely to be associated with other medical complications. 


Risk and Prognostic Factors 


Environmental. 
Environmental 
risk and prognostic factors may include poverty and 
discrimination (including structural 
inequities such as differential 
incarceration rates and 
differential 
access to medications for addiction treatment), unemployment 
and low levels of 
education, cultural 
attitudes toward drinking and intoxication, the availability of alcohol 
(including price), acquired personal 
experiences with alcohol, and stress levels. Additional 
potential 
mediators of how alcohol 
problems develop in predisposed individuals include heavier 
peer substance use, exaggerated positive expectations of the effects of alcohol, and suboptimal 
ways of coping with stress. 


Genetic 
and 
physiological. 


Alcohol use disorder runs in families, with 40% 60% of the variance of 
risk explained by genetic influences. The rate of this condition is three to four times higher in 
close relatives of individuals with alcohol 
use disorder, with values highest 
for individuals with a 
greater number of affected relatives, closer genetic relationships to the affected individual, and 
higher severity of the alcohol-related problems in those relatives. A significantly higher rate of 
alcohol 
use disorder exists in the monozygotic twin than in the dizygotic twin of an individual 
with the condition. A three- to fourfold increase in risk has been observed in children of 
individuals with alcohol 
use disorder, even when these children were given up for adoption at 
birth and raised by adoptive parents who did not have the disorder. 


Advances in understanding the genes that 
operate through intermediate characteristics (or 
phenotypes) to affect 
the risk of alcohol 
use disorder can help to identify individuals who might 
be at 
particularly low or high risk for alcohol 
use disorder. Among the low-risk phenotypes is the 
acute alcohol-related skin flush (seen more commonly in persons of Asian descent). High 
vulnerability is associated with preexisting schizophrenia or bipolar disorder, as well 
as 
impulsivity (producing enhanced rates of all 
substance use disorders and gambling disorder), and 
a high risk specifically for alcohol 
use disorder is associated with a low level 
of response (low 



sensitivity) to alcohol. A number of gene variations may account 
for low response to alcohol 
or 
modulate the dopamine reward systems; 
however, any single gene variant 
is likely to explain 
only 1% 2% of the risk for these disorders. Gene-environment 
interactions modulate the impact 
of genetic variations; for 


558 


example, genetic effects on alcohol 
use are more pronounced when social 
constraints are 
minimized (e.g., low parental 
monitoring) or when the environment 
permits easy access to 
alcohol or encourages its use (e.g., high peer deviance). 


Course 
modifiers. 
In general, high levels of impulsivity are associated with an earlier onset 
and 
more severe alcohol use disorder. 


Culture-Related Diagnostic Issues 


In most 
cultures, alcohol 
is the most 
frequently used intoxicating substance and contributes to 
considerable morbidity and mortality. Globally, 2.8 million deaths were attributed to alcohol 
use, 
which corresponds to 2.2% of total 
age-standardized deaths among women and 6.8% among 
men. Globally, an estimated 237 million men and 46 million women have alcohol 
use disorder, 
with the highest 
prevalence being among men and women in the European Region (14.8% and 
3.5%) and the Region of the Americas (11.5% and 5.1%); in general, high-income countries have 
the highest 
prevalence. Greater acculturation to U.S. society among immigrants is associated 
with rising prevalence of alcohol 
use disorder, especially among women. Ethnic density (greater 
proportion of people from 
the same background) may decrease the risk of alcohol 
use disorder 
because of greater social 
support 
and buffering against 
the effects of discrimination. However, 
neighborhood segregation may increase the risk for disorders because of the association with 
other risk factors, such as higher concentration of alcohol 
advertising and retail 
outlets in low-
income areas. 


Genetic polymorphisms for the alcohol-metabolizing enzymes alcohol 
dehydrogenase and 
aldehyde dehydrogenase may affect 
the response to alcohol. When consuming alcohol, 
individuals with certain polymorphisms can experience a flushed face and palpitations, reactions 
that 
can be so severe as to limit 
or preclude future alcohol 
consumption and diminish the risk for 
alcohol 
use disorder. For example, these gene variations are seen in as many as 40% of Japanese, 
Chinese, and Korean individuals and are related to lower risks for the disorder. However, this 
protective effect 
may be modulated by sociocultural 
factors, as shown by rising prevalence of 
alcohol 
use disorder in Japan, China, and South Korea over the last 
decades associated with 
increasing westernization and changing cultural attitudes about women s drinking. 


Despite small 
variations regarding individual 
criterion items, the diagnostic criteria perform 
equally well across most race/ethnicity groups. 


Sex- and Gender-Related Diagnostic Issues 


Men have higher rates of drinking and alcohol 
use disorder than women, although the gender gap 
is narrowing as women are initiating alcohol 
use at 
a younger age. Because females generally 
weigh less than males, have more fat 
and less water in their bodies, and metabolize less alcohol 
in their esophagus and stomach, they are likely to develop higher blood alcohol 
levels per drink 



than males. Females who drink heavily may also be more vulnerable than males to some of the 
physical 
consequences associated with alcohol, including alcohol-related blackouts and liver 
disease. Additionally, while genetic-related mechanisms for alcohol 
risk overlap for males and 
females, the specific environmental 
components that 
add to the risk may differ across sexes, 
especially during adolescence. Drinking during pregnancy, which tends to decrease overall, may 
be a sign of an alcohol use disorder. 


Diagnostic Markers 


Individuals whose heavier drinking places them 
at 
elevated risk for alcohol 
use disorder can be 
identified both through standardized questionnaires and by elevations in blood test 
results likely 
to be seen with regular heavier drinking. These measures do not 
establish a diagnosis of an 
alcohol-related disorder but can be useful in highlighting individuals for 


559 


whom 
more information should be gathered. The most 
direct 
test 
available to measure alcohol 
consumption cross-sectionally is blood alcohol 
concentration, 
which can also be used to judge 
tolerance to alcohol. For example, an individual 
with a concentration of 150 mg of ethanol 
per 
deciliter (dL) of blood who does not 
show signs of intoxication can be presumed to have 
acquired at 
least 
some degree of tolerance to alcohol. At 
200 mg/dL, most 
nontolerant 
individuals demonstrate severe intoxication. 


Regarding laboratory tests, one sensitive laboratory indicator of heavy drinking is a modest 
elevation or high-normal 
levels (>35 units) of gamma-glutamyltransferase (GGT). This may be 
the only laboratory finding. At 
least 
70% of individuals with a high GGT 
level 
are persistent 
heavy drinkers (i.e., consuming eight 
or more drinks daily on a regular basis). A second test 
with 
comparable or even higher levels of sensitivity and specificity is carbohydrate-deficient 
transferrin (CDT), with levels of 20 units or higher useful 
in identifying individuals who 
regularly consume eight 
or more drinks daily. Given that 
both GGT 
and CDT 
levels return 
toward normal 
within days to weeks of stopping drinking, both state markers may be useful 
in 
monitoring abstinence, especially when the clinician observes increases, rather than decreases, in 
these values over time a finding indicating that 
the individual 
is likely to have returned to 
heavy drinking. The combination of tests for CDT 
and GGT 
may have even higher levels of 
sensitivity and specificity than either test 
used alone. Additional 
useful 
tests include the mean 
corpuscular volume (MCV), which may be elevated to high-normal 
values in individuals who 
drink heavily a change that 
is due to the direct 
toxic effects of alcohol 
on erythropoiesis. 
Although the MCV can be used to help identify those who drink heavily, it 
is a poor method of 
monitoring abstinence because of the long half-life of red blood cells. Liver function tests (e.g., 
alanine aminotransferase and alkaline phosphatase) can reveal 
liver injury that 
is a consequence 
of heavy drinking. Other potential 
markers of heavy drinking that 
are more nonspecific for 
alcohol 
but 
can help the clinician think of the possible effects of alcohol 
include elevations in 
blood levels or lipids (e.g., triglycerides and high-density lipoprotein cholesterol) and high-
normal levels of uric acid. 


Additional 
diagnostic markers relate to signs and symptoms that 
reflect 
the consequences 
often associated with persistent 
heavy drinking. For example, dyspepsia, nausea, and bloating 



can accompany gastritis, and hepatomegaly, esophageal 
varices, and hemorrhoids may reflect 
alcohol-induced changes in the liver. Other physical 
signs of heavy drinking include tremor, 
unsteady gait, insomnia, and erectile dysfunction. Males with chronic alcohol 
use disorder may 
exhibit 
decreased testicular size and feminizing effects associated with reduced testosterone 
levels. Repeated heavy drinking in females is associated with menstrual 
irregularities and, during 
pregnancy, spontaneous abortion and fetal 
alcohol 
syndrome. Individuals with preexisting 
histories of epilepsy or severe head trauma are more likely to develop alcohol-related seizures. 
Alcohol 
withdrawal 
may be associated with nausea, vomiting, gastritis, hematemesis, dry mouth, 
puffy blotchy complexion, and mild peripheral edema. 


Association With Suicidal 
Thoughts or Behavior 


Most 
studies on suicidality and alcohol 
address alcohol 
consumption rather than alcohol 
use 
disorder. However, a psychological 
autopsy study in Australia found that 
aggression, psychiatric 
comorbidity, and recent 
interpersonal 
conflicts are suicide risk factors in individuals with alcohol 
use disorder. A review of studies from 
1999 through 2014 conducted in several 
countries, 
including the United States, reported that 
both intoxication and chronic heavy alcohol 
use are 
associated with suicide, extensive population-level 
data link alcohol 
with suicide, and there is 
evidence suggesting that 
restrictive alcohol 
policies may help prevent 
suicide on a general 
population level. A meta-analysis of studies conducted in the United States and several 
other 
countries from 
1996 through 2015 found that 
compared with nondrinking individuals, the acute 
use of alcohol was associated with a nearly 


560 


sevenfold increase in risk of suicide attempt. Moreover, in this meta-analysis, as well 
as in U.S.based 
case-control 
crossover studies, heavier alcohol 
use within 24 hours was a much more 
potent 
risk factor for suicide attempt 
than lower alcohol 
use. In a cohort 
of patients in 
Mississippi, acute co-use of alcohol 
and sedatives had an even stronger association with suicide 
attempt 
compared with alcohol 
use alone. A systematic review and meta-analysis of studies from 
1975 through 2014 in several 
countries, including the United States, found that 
alcohol 
use is 
associated with possession of firearms, that 
alcohol 
drinkers are four to six times more likely to 
die by suicide with a gun than nondrinkers, and that 
heavy drinkers are more likely to choose 
firearms over other suicide methods compared with nondrinkers. 


Functional 
Consequences of Alcohol 
Use Disorder 


The diagnostic features of alcohol 
use disorder highlight 
major areas of life functioning likely to 
be impaired. These include driving and operating machinery, school 
and work, interpersonal 
relationships and communication, and health. Alcohol-related disorders contribute to 
absenteeism 
from 
work, job-related accidents, and low employee productivity. Rates are elevated 
in homeless individuals, perhaps reflecting a downward spiral 
in social 
and occupational 
functioning, although most 
individuals with alcohol 
use disorder continue to live with their 
families and function within their jobs. 


Alcohol 
use disorder is associated with a significant 
increase in the risk of accidents, 
violence, and suicide. It is estimated that one in five intensive care unit admissions in some urban 



hospitals is related to alcohol 
and that 
40% of individuals in the United States experience an 
alcohol-related adverse event 
at 
some time in their lives, with alcohol 
accounting for up to 55% 
of fatal 
driving events. Severe alcohol 
use disorder, especially in individuals with antisocial 
personality disorder, is associated with the commission of criminal 
acts, including homicide. 
Severe problematic alcohol 
use also contributes to disinhibition and feelings of sadness and 
irritability, which contribute to suicide attempts and suicide. 


Unanticipated alcohol 
withdrawal 
in hospitalized individuals 
for whom 
a diagnosis of 
alcohol 
use disorder has been overlooked can add to the risks and costs of hospitalization and to 
time spent in the hospital. 


Differential 
Diagnosis 


Nonpathological 
use 
of 
alcohol. 
The key element 
of alcohol 
use disorder is the use of heavy doses 
of alcohol 
with resulting repeated and significant 
distress or impaired functioning. While most 
drinkers sometimes consume enough alcohol 
to feel 
intoxicated, only a minority (< 20%) ever 
develop alcohol 
use disorder. Therefore, drinking, even daily, in low doses and occasional 
intoxication do not by themselves make this diagnosis. 


Alcohol 
intoxication, 
alcohol 
withdrawal, 
and 
alcohol-induced 
mental 
disorders. 


Alcohol 
use disorder is 
differentiated from 
alcohol 
intoxication, alcohol 
withdrawal, and alcohol 
induced mental 
disorders (e.g., alcohol-induced depressive disorder) in that 
alcohol 
use disorder describes a 
problematic pattern of alcohol 
use that 
involves impaired control 
over alcohol 
use, social 
impairment 
due to alcohol 
use, risky alcohol 
use (e.g., driving while intoxicated), and 
pharmacological 
symptoms (the development 
of tolerance or withdrawal), whereas alcohol 
intoxication, alcohol 
withdrawal, and alcohol-induced mental 
disorders describe psychiatric 
syndromes that 
develop in the context 
of heavy use. Alcohol 
intoxication, alcohol 
withdrawal, 
and alcohol-induced mental 
disorders occur frequently in individuals with alcohol 
use disorder. 
In such cases, a diagnosis of alcohol 
intoxication, alcohol 
withdrawal, or an alcohol-induced 
mental disorder should be given in addition to 


561 


a diagnosis of alcohol use disorder, the presence of which is indicated in the diagnostic code. 


Sedative, 
hypnotic, 
or anxiolytic 
use 
disorder. 
The signs and symptoms of alcohol 
use disorder are 
similar to those seen in sedative, hypnotic, or anxiolytic use disorder. The two must 
be 
distinguished, however, because the course may be different, especially in relation to medical 
problems. 
Conduct 
disorder in 
childhood 
and 
antisocial 
personality 
disorder. 
Alcohol 
use disorder, along with 


other substance use disorders, is seen in the majority of individuals with antisocial 
personality 
disorder and preexisting conduct 
disorder. Because these diagnoses are associated with an early 
onset 
of alcohol 
use disorder as well 
as a worse prognosis, it 
is important 
to establish both 
conditions. 


Comorbidity 


Bipolar disorders, schizophrenia, and antisocial 
personality disorder are associated with alcohol 



use disorder, and most 
anxiety and depressive disorders are associated with alcohol 
use disorder 
as well. At 
least 
a part 
of the reported association between depression and moderate to severe 
alcohol 
use disorder may be attributable to temporary, alcohol-induced comorbid depressive 
symptoms resulting from 
the acute effects of intoxication or withdrawal, although this point 
has 
long been debated. Severe, repeated alcohol 
intoxication may also suppress immune mechanisms 
and predispose individuals to infections and increase the risk for cancers. 


Alcohol 
Intoxication 


Diagnostic Criteria 


A. 
Recent 
ingestion 
of 
alcohol. 
B. 
Clinically significant 
problematic behavioral or psychological changes (e.g., 
inappropriate 
sexual or aggressive 
behavior, 
mood 
lability, 
impaired 
judgment) 
that 
developed 
during, 
or shortly after, 
alcohol ingestion. 
C. 
One 
(or more) of 
the 
following 
signs or symptoms developing 
during, 
or shortly 
after, 
alcohol use: 
1. 
Slurred 
speech. 
2. 
Incoordination. 
3. 
Unsteady gait. 
4. 
Nystagmus. 
5. 
Impairment 
in 
attention 
or memory. 
6. 
Stupor or coma. 
D. 
The 
signs or symptoms are 
not 
attributable 
to 
another medical condition 
and 
are 
not 
better explained 
by another mental disorder, 
including 
intoxication 
with 
another substance. 
Coding 
note: 
The 
ICD-10-CM code 
depends on 
whether there 
is a 
comorbid 
alcohol 
use 
disorder. 
If 
a 
mild 
alcohol use 
disorder is comorbid, 
the 
ICD-10-CM code 
is 
F10.120, 
and 
if 
a 
moderate 
or severe 
alcohol use 
disorder is comorbid, 
the 
ICD-10CM 
code 
is F10.220. 
If 
there 
is no 
comorbid 
alcohol use 
disorder, 
then 
the 
ICD-10CM 
code 
is F10.920. 


562 


Diagnostic Features 


The essential 
feature of alcohol 
intoxication is the presence of clinically significant 
and 
sometimes life-threatening problematic behavioral 
or psychological 
changes (e.g., inappropriate 
sexual 
or aggressive behavior, mood lability, impaired judgment 
and decision-making, 
difficulties with complex tasks such as driving, and impaired social 
or occupational 
functioning) 
that 
develop during, or shortly after, alcohol 
ingestion (Criterion B). These changes are 



accompanied by evidence of impaired functioning and judgment 
and, if intoxication is intense, 
can result 
in a life-threatening coma. The symptoms must 
not 
be attributable to another medical 
condition (e.g., diabetic ketoacidosis), are not 
a reflection of conditions such as delirium, and are 
not 
related to intoxication with other depressant 
drugs (e.g., benzodiazepines) (Criterion D). The 
levels of incoordination can interfere with driving abilities and performance of usual 
activities to 
the point 
of causing vehicle crashes or other events resulting in 
injury. Evidence of alcohol 
use 
can be obtained by smelling alcohol 
on the individual s breath, eliciting a history from 
the 
individual 
or another observer, and, when needed, having the individual 
provide breath, blood, or 
urine samples for toxicology analyses. 


Associated Features 


Signs and symptoms of intoxication are likely to be more intense when the blood alcohol 
level 
is 
rising than when it 
is falling. The duration of intoxication depends on how much alcohol 
was 
consumed over what 
period of time. In general, the body is able to metabolize approximately one 
drink per hour, so that 
the blood alcohol 
level 
generally decreases at 
a rate of 15 20 mg/dL 
per 
hour. 


During even mild alcohol 
intoxication, different 
symptoms are likely to be observed at 
different 
time points. Evidence of mild intoxication with alcohol 
can be seen in most 
individuals 
after approximately two drinks (each standard drink is approximately 10 12 grams of ethanol 
and raises the blood alcohol 
concentration approximately 20 mg/dL). Early in the drinking 
period, when blood alcohol 
levels are rising, symptoms often reflect 
stimulation (e.g., 
talkativeness, a sensation of well-being, a bright, expansive mood). Later, especially when blood 
alcohol 
levels are falling, the individual 
is likely to become progressively more depressed, 
withdrawn, and cognitively impaired. 


Alcohol 
intoxication is sometimes associated with amnesia for the events that 
occurred 
during the course of the intoxication ( blackouts ). This phenomenon is related to a relatively 
high blood alcohol 
level 
and, perhaps, to the rapidity with which this level 
is reached. Acute 
alcohol 
intoxication may cause metabolic alterations (e.g., hypoglycemia, electrolyte 
disturbances) and may have severe cardiovascular, respiratory, and/or gastrointestinal 
effects. At 
very high blood alcohol 
levels (e.g., 200 300 mg/dL), an individual 
who has not 
developed 
tolerance for alcohol 
is likely to fall 
asleep and enter a first 
stage of anesthesia. Higher blood 
alcohol 
levels (e.g., in excess of 300 400 mg/dL) can cause inhibition of respiration and pulse 
and even death in nontolerant individuals. 


Alcohol 
intoxication is an important 
contributor to interpersonal 
violence and suicidal 
behavior. Among individuals intoxicated by alcohol, there appears to be an increased rate of 
accidental 
injury (including death due to behaviors associated with altered judgment, self-harm, 
and violence), suicidal behavior, and suicide. 


Prevalence 


The large majority of alcohol 
consumers are likely to have been intoxicated to some degree at 
some point 
in their lives. For example, in 2018, 43% of 12th-grade students in the United States 
reported having  been drunk  at least once in their lifetime, and 17.5% of them reported that they 
had gotten drunk at 
least 
once in the prior 30 days. Using a definition of intoxication of four or 
more standard drinks on any day for women and five or more 



563 


standard drinks on any day for men, the 12-month prevalence of high-risk drinking in U.S. adults 
is 17.4% for Native Americans, 15.1% for African Americans, 13.5% for Latinx, 12.3% for non-
Latinx Whites, and 7.2% for Asians and Pacific Islanders. 


Development and Course 


Intoxication usually occurs as an episode developing over minutes to hours and typically lasting 
several 
hours. In the United States, the average age at 
first 
intoxication is approximately 15 
years, with the highest 
prevalence at 
approximately 18 25 years. Frequency and intensity usually 
decrease with further advancing age. The earlier the onset 
of regular intoxication, the greater the 
likelihood the individual will go on to develop alcohol use disorder. 


Risk and Prognostic Factors 


Temperamental. 


Episodes of alcohol 
intoxication increase with personality characteristics of sensation seeking 
and impulsivity. 


Environmental. 


Episodes of alcohol 
intoxication increase with having heavy-drinking peers, holding beliefs that 
heavy drinking is an important component of having fun, and using alcohol to cope with stress. 


Culture-Related Diagnostic Issues 


The major issues parallel 
the cultural 
differences regarding the use of alcohol 
overall. For 
example, some college fraternities and sororities encourage alcohol 
intoxication. This condition 
is also frequent 
on certain dates of cultural 
significance (e.g., New Year s Eve) and, for some 
subgroups, during specific events (e.g., wakes following funerals). Other subgroups encourage 
drinking at 
religious celebrations (e.g., Jewish and Catholic holidays), while still 
others strongly 
discourage all 
drinking or intoxication (e.g., some religious groups, such as Mormons, 
fundamentalist Christians, and Muslims). 


Sex- and Gender-Related Diagnostic Issues 


Historically, in many Western societies, acceptance of drinking and drunkenness is more 
tolerated for men, but 
such gender differences may be much less prominent 
in recent 
years, 
especially during adolescence and young adulthood. In general, women are less tolerant 
of the 
same amount of alcohol than men. 


Diagnostic Markers 


Intoxication is usually established by observing an individual s behavior and smelling alcohol 
on 
the breath. The degree of intoxication increases with an individual s blood or breath alcohol 
level 
and with the ingestion of other substances, especially those with sedating effects. 



Association With Suicidal 
Thoughts or Behavior 


A collaborative, international 
study in emergency departments in 17 countries found that 
acute 
alcohol 
use, independent 
of chronic use, increases the risk of suicide attempt, with each drink 
raising the risk by 30%. For more information, see  Association With Suicidal 
Thoughts or 
Behavior  in the Alcohol Use Disorder section. 


Functional 
Consequences of Alcohol 
Intoxication 


Alcohol 
intoxication contributed to the more than 95,000 deaths and 2.8 million years of 
potential life lost each year in the United States from 2011 through 2015, shortening the 


564 


lives of those who died by an average of 30 years. In addition, intoxication with this drug 
contributes to huge costs associated with drunk driving and lost 
time from 
school 
or work, as 
well as interpersonal arguments and physical fights. 


Differential 
Diagnosis 


Other medical 
conditions. 
Several 
medical 
(e.g., diabetic acidosis) and neurological 
conditions 


(e.g., cerebellar ataxia, multiple sclerosis) can temporarily resemble alcohol intoxication. 
Alcohol-induced 
mental 
disorders. 
Alcohol 
intoxication is distinguished from 
alcohol-induced 
mental 
disorders (e.g., alcohol-induced depressive disorder, with onset 
during intoxication) 
because the symptoms (e.g., depressed mood) in these latter disorders are in excess of those 
usually associated with alcohol 
intoxication, predominate in the clinical 
presentation, and are 
severe enough to warrant clinical attention. 


Sedative, 
hypnotic, 
or anxiolytic 
intoxication. 
Intoxication with sedative, hypnotic, or anxiolytic 
drugs or with other sedating substances (e.g., antihistamines, anticholinergic drugs) can be 
mistaken for alcohol 
intoxication. The differential 
requires observing alcohol 
on the breath, 
measuring blood or breath alcohol 
levels, ordering a medical 
workup, and gathering a good 
history. The signs and symptoms of sedative-hypnotic intoxication are very similar to those 
observed with alcohol 
and include similar problematic behavioral 
or psychological 
changes. 
These changes are accompanied by evidence of impaired functioning and judgment which, if 
intense, can result in a life-threatening coma and levels of incoordination that can interfere with 
driving abilities and with performing usual 
activities. However, there is no smell 
as there is with 
alcohol, but 
there is likely to be evidence of misuse of the depressant 
drug in the blood or urine 
toxicology analyses. 


Comorbidity 


Alcohol 
intoxication may occur comorbidly with other substance intoxication, especially in 
individuals with conduct 
disorder or antisocial 
personality disorder. Given the typical 
overlap of 
alcohol 
intoxication with alcohol 
use disorder, see  Comorbidity  under Alcohol 
Use Disorder 
for more details about co-occurring conditions that are likely to be encountered. 



Alcohol 
Withdrawal 


Diagnostic Criteria 


A. 
Cessation 
of 
(or reduction 
in) alcohol use 
that 
has been 
heavy and 
prolonged. 
B. 
Two 
(or more) of 
the 
following, 
developing 
within 
several hours to 
a 
few days 
after the 
cessation 
of 
(or reduction 
in) alcohol use 
described 
in 
Criterion 
A: 
1. 
Autonomic hyperactivity (e.g., 
sweating 
or pulse 
rate 
greater than 
100 
bpm). 
2. 
Increased 
hand 
tremor. 
3. 
Insomnia. 
4. 
Nausea 
or vomiting. 
5. 
Transient 
visual, 
tactile, 
or auditory hallucinations or illusions. 
6. 
Psychomotor agitation. 
7. 
Anxiety. 
8. 
Generalized 
tonic-clonic seizures. 
C. 
The 
signs or symptoms in 
Criterion 
B 
cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
565 


D. 
The 
signs or symptoms are 
not 
attributable 
to 
another medical condition 
and 
are 
not 
better explained 
by another mental disorder, 
including 
intoxication 
or 
withdrawal from another substance. 
Specify 
if: 
With 
perceptual 
disturbances: 
This specifier applies in 
the 
rare 
instance 
when 
hallucinations (usually visual or tactile) occur with 
intact 
reality testing, 
or 
auditory, 
visual, 
or tactile 
illusions occur in 
the 
absence 
of 
a 
delirium. 
Coding 
note: 
The 
ICD-10-CM code 
depends on 
whether or not 
there 
is a 
comorbid 
alcohol use 
disorder and 
whether or not 
there 
are 
perceptual disturbances. 
For alcohol 
withdrawal, 
without perceptual 
disturbances: 
If 
a 
mild 
alcohol 
use 
disorder is comorbid, 
the 
ICD-10-CM code 
is F10.130, 
and 
if 
a 
moderate 
or 


severe 
alcohol use 
disorder is comorbid, 
the 
ICD-10-CM code 
is F10.230. 
If 
there 
is no 
comorbid 
alcohol use 
disorder, 
then 
the 
ICD-10-CM code 
is F10.930. 
For alcohol 
withdrawal, 
with 
perceptual 
disturbances: 
If 
a 
mild 
alcohol use 


disorder is comorbid, 
the 
ICD-10-CM code 
is F10.132, 
and 
if 
a 
moderate 
or 
severe 
alcohol use 
disorder is comorbid, 
the 
ICD-10-CM code 
is F10.232. 
If 
there 
is no 
comorbid 
alcohol use 
disorder, 
then 
the 
ICD-10-CM code 
is F10.932. 


Specifiers 



When hallucinations occur in the absence of delirium 
(i.e., in a clear sensorium), a diagnosis of 
substance/medication-induced psychotic disorder should be considered. 


Diagnostic Features 


The essential 
feature of alcohol 
withdrawal 
is the presence of a characteristic withdrawal 
syndrome that 
develops within several 
hours to a few days after the cessation of (or reduction in) 
heavy and prolonged alcohol 
use (Criteria A and B). The withdrawal 
syndrome includes two or 
more of the symptoms reflecting autonomic hyperactivity and anxiety listed in Criterion B, along 
with gastrointestinal symptoms. 


Withdrawal 
symptoms cause clinically significant 
distress or impairment 
in social, 
occupational, or other important 
areas of functioning (Criterion C). The symptoms must 
not 
be 
attributable to another medical 
condition and are not 
better explained by another mental 
disorder 
(e.g., generalized anxiety disorder), including intoxication or withdrawal 
from 
another substance 
(e.g., sedative, hypnotic, or anxiolytic withdrawal) (Criterion D). 


Symptoms can be relieved by administering alcohol 
or benzodiazepines (e.g., diazepam). The 
withdrawal 
symptoms typically begin when blood concentrations of alcohol 
decline sharply (i.e., 
within 4 12 hours) after alcohol 
use has been stopped or reduced. Reflecting the relatively fast 
metabolism 
of alcohol, symptoms of alcohol 
withdrawal 
usually peak in intensity during the 
second day of abstinence and are likely to improve markedly by the fourth or fifth day. 
Following acute withdrawal, however, symptoms of anxiety, insomnia, and autonomic 
dysfunction may persist for up to 3 6 months at lower levels of intensity. 


Fewer than 10% of individuals who develop alcohol 
withdrawal 
will 
ever develop dramatic 
symptoms (e.g., severe autonomic hyperactivity, tremors, alcohol 
withdrawal 
delirium). Tonicclonic 
seizures occur in fewer than 3% of individuals. 


Associated Features 


Although confusion and changes in consciousness are not 
core criteria for alcohol 
withdrawal, 
alcohol 
withdrawal 
delirium 
(see  Delirium  in the chapter  Neurocognitive Disorders ) may 
occur in the context 
of withdrawal. As is true for any agitated, confused state, regardless of the 
cause, in addition to a disturbance of consciousness and cognition, withdrawal 
delirium 
can 
include visual, tactile, or (rarely) auditory hallucinations 


566 


(delirium 
tremens). When alcohol 
withdrawal 
delirium 
develops, it 
is likely that 
a clinically 
relevant 
medical 
condition may be present 
(e.g., liver failure, pneumonia, gastrointestinal 
bleeding, sequelae of head trauma, hypoglycemia, an electrolyte imbalance, postoperative 
status). 


Prevalence 


It 
is estimated that 
approximately 50% of middle-class, highly functional 
individuals with 
alcohol 
use disorder in the United States have ever experienced a full 
alcohol 
withdrawal 
syndrome. Among individuals with alcohol 
use disorder who are hospitalized or homeless, the 
rate of alcohol 
withdrawal 
may be greater than 80%. Less than 10% of individuals in withdrawal 



ever demonstrate alcohol 
withdrawal 
delirium 
or withdrawal 
seizures. The prevalence of alcohol 
withdrawal symptoms does not seem to vary across U.S. ethnoracial groups. 


Development and Course 


Acute alcohol 
withdrawal 
occurs as an episode usually lasting 4 5 days and only after extended 
periods of heavy drinking. Withdrawal 
is relatively rare in individuals younger than 30 years, 
and the risk and severity increase with increasing age. 


Risk and Prognostic Factors 


Alcohol 
withdrawal 
is more likely to occur with heavier alcohol 
intake, and that 
might 
be most 
often observed in individuals with conduct 
disorder and antisocial 
personality disorder. 
Withdrawal 
states are also more severe in individuals who are also dependent 
on other 
depressant 
drugs (sedative-hypnotics) and individuals who have had more alcohol 
withdrawal 
experiences in the past. Predictors of severe alcohol 
withdrawal 
include alcohol 
withdrawal 
delirium, prior histories of severe withdrawal 
syndromes, low blood potassium 
levels, decreased 
platelet counts, and systolic hypertension. 


Environmental. 
The probability of developing alcohol 
withdrawal 
increases with the quantity and 
frequency of alcohol 
consumption. Most 
individuals with this condition are drinking daily, 
consuming large amounts (approximately more than eight 
drinks per day) for multiple days. 
However, there are large inter-individual 
differences, with enhanced risks for individuals with 
concurrent 
medical 
conditions, those with family histories of alcohol 
withdrawal 
(i.e., a genetic 
component), those with prior withdrawals, and individuals who consume sedative, hypnotic, or 
anxiolytic drugs. 


Diagnostic Markers 


Autonomic hyperactivity in the context 
of moderately high but 
falling blood alcohol 
levels and a 
history of prolonged, heavy drinking indicate a likelihood of alcohol withdrawal. 


Functional 
Consequences of Alcohol 
Withdrawal 


Symptoms of withdrawal 
may serve to perpetuate drinking behaviors and contribute to relapse, 
resulting in persistently impaired social 
and occupational 
functioning. Symptoms requiring 
medically supervised detoxification result 
in hospital 
utilization and loss of work productivity. 
Overall, the presence of withdrawal 
is associated with greater functional 
impairment 
and poor 
prognosis among individuals with alcohol use disorder. 


Differential 
Diagnosis 


Other medical 
conditions. 
The symptoms of alcohol 
withdrawal 
can also be mimicked by some 
medical conditions (e.g., hypoglycemia and diabetic ketoacidosis). Essential tremor, 


567 


a disorder that 
frequently runs in families, may erroneously suggest 
the tremulousness associated 
with alcohol withdrawal. 



Alcohol-induced 
mental 
disorders. 
Alcohol 
withdrawal 
is distinguished from 
alcohol-induced 
mental 
disorders (e.g., alcohol-induced anxiety disorder, with onset 
during withdrawal) because 
the symptoms (e.g., anxiety) in these latter disorders are in excess of those usually associated 
with alcohol 
withdrawal, predominate in the clinical 
presentation, and are severe enough to 
warrant clinical attention. 


Sedative, 
hypnotic, 
or anxiolytic 
withdrawal. 
Sedative, hypnotic, or anxiolytic withdrawal 
produces a 
syndrome very similar to that of alcohol withdrawal. 


Comorbidity 


Given the typical 
overlap of alcohol 
withdrawal 
with alcohol 
use disorder, see  Comorbidity  
under Alcohol 
Use Disorder for more details about 
co-occurring conditions that 
are likely to be 
encountered. 


Alcohol-Induced 
Mental 
Disorders 


The following alcohol-induced mental 
disorders are described in other chapters of the manual 
with disorders with which they share phenomenology (see the substance/medication-induced 
mental 
disorders in these chapters): 
alcohol-induced psychotic disorder ( Schizophrenia 
Spectrum 
and Other Psychotic Disorders ); 
alcohol-induced bipolar and related disorder 
( Bipolar and Related Disorders ); 
alcohol-induced depressive disorder ( Depressive 
Disorders ); 
alcohol-induced anxiety disorder ( Anxiety Disorders ); 
alcohol-induced sleep 
disorder ( Sleep-Wake Disorders ); 
alcohol-induced sexual 
dysfunction ( Sexual 
Dysfunctions ); 
and alcohol-induced major or mild neurocognitive disorder ( Neurocognitive 
Disorders ). For alcohol 
intoxication delirium 
and alcohol 
withdrawal 
delirium, see the criteria 
and discussion of delirium 
in the chapter  Neurocognitive Disorders.  These alcohol-induced 
mental 
disorders are diagnosed instead of alcohol 
intoxication or alcohol 
withdrawal 
only when 
the symptoms are sufficiently severe to warrant independent clinical attention. 


Diagnostic and Associated Features 


The symptom 
profiles for an alcohol-induced condition resemble the corresponding independent 
mental 
disorders as described elsewhere in this manual. Moreover, while alcohol-induced 
conditions can have the same severe consequences as independent 
mental 
disorders (e.g., suicide 
attempts), they are likely to improve without 
formal 
treatment 
in a matter of days to weeks after 
cessation of severe intoxication and/or withdrawal. 


Each alcohol-induced mental disorder is listed in the relevant diagnostic section and therefore 
only a brief description is offered here. These alcohol-induced mental 
disorders must 
have 
developed in the context of severe alcohol intoxication and/or alcohol withdrawal. 


Given that 
the presentation of an alcohol-induced mental 
disorder symptomatically resembles 
the presentations of independent 
mental 
disorders from 
the same diagnostic class, they must 
be 
differentiated based on the temporal 
relationship between the alcohol 
use and the psychiatric 
symptoms. Individuals with alcohol-induced mental 
disorders are likely to also demonstrate the 
associated features seen with an alcohol use disorder, as listed in that subsection. 


There must 
be evidence that 
the disorder being observed is not likely to be better explained 



by an independent mental disorder. The latter is likely to occur if the mental 


568 


disorder was present 
before the severe intoxication or withdrawal, or continued for more than 
1 month after the cessation of severe intoxication or withdrawal. When symptoms are observed 
only during a delirium, they should be considered part 
of the delirium 
and not 
diagnosed 
separately, as many symptoms (including disturbances in mood, anxiety, and reality testing) are 
commonly seen during agitated, confused states. The alcohol-induced mental 
disorder must 
be 
clinically relevant, causing significant distress or significant functional impairment. Finally, there 
are indications that 
the intake of substances of abuse in the context 
of a preexisting mental 
disorder are likely to result in an intensification of the preexisting independent syndrome. 


Rates of alcohol-induced mental 
disorders vary somewhat 
by diagnostic category. For 
example, the lifetime risk for major depressive episodes in individuals with alcohol 
use disorder 
is approximately 40%, but 
only about 
one-third to one-half of these represent 
independent 
major 
depressive syndromes observed outside the context 
of intoxication. Similar rates of alcohol-
induced sleep and anxiety disorders are likely, but 
alcohol-induced psychotic episodes are 
estimated to be seen in less than 5% of individuals with alcohol use disorder. 


Development 
and Course 


Once present, the symptoms of an alcohol-induced mental 
disorder are likely to remain clinically 
relevant 
as long as the individual 
continues to experience severe intoxication or withdrawal. 
While the symptoms may be identical 
to those of independent 
mental 
disorders (e.g., psychoses, 
major depressive disorder), and while they can have the same severe consequences (e.g., suicide 
attempts), all 
alcohol-induced mental 
disorders other than alcohol-induced neurocognitive 
disorder, amnestic confabulatory type (alcohol-induced persisting amnestic disorder), regardless 
of the severity of the symptoms, are likely to improve relatively quickly and unlikely to remain 
clinically relevant 
for more than 1 month after cessation of severe intoxication and/or 
withdrawal. 


The alcohol-induced mental 
disorders are an important 
part 
of the differential 
diagnoses for 
the independent 
mental 
conditions. Independent 
schizophrenia, major depressive disorder, 
bipolar disorder, and anxiety disorders, such as panic disorder, are likely to be associated with 
much longer-lasting periods of symptoms and often require longer-term 
medications to optimize 
the probability of improvement 
or recovery. The alcohol-induced mental 
disorders, on the other 
hand, are likely to be much shorter in duration and disappear within several 
days to 1 month after 
cessation of severe intoxication and/or withdrawal, even without psychotropic medications. 


The importance of recognizing an alcohol-induced mental 
disorder is similar to the relevance 
of identifying the possible role of some endocrine conditions and medication reactions before 
diagnosing an independent 
mental 
disorder. In light 
of the high prevalence of alcohol 
use 
disorders worldwide, it 
is important 
that 
these alcohol-induced diagnoses be considered before 
independent mental disorders are diagnosed. 


Unspecified 
Alcohol-Related 
Disorder 



F10.99 


This category applies to 
presentations in 
which 
symptoms characteristic of 
an 
alcohol-related 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any specific alcohol-related 
disorder or any of 
the 
disorders 
in 
the 
substance-related 
and 
addictive 
disorders diagnostic class. 


569 


Caffeine-Related Disorders 


Caffeine 
Intoxication 
Caffeine 
Withdrawal 
Caffeine-Induced 
Mental Disorders 
Unspecified 
Caffeine-Related 
Disorder 


Caffeine Intoxication 


Diagnostic Criteria 
F15.920 


A. 
Recent 
consumption 
of 
caffeine 
(typically a 
high 
dose 
well in 
excess of 
250 
mg). 
B. 
Five 
(or more) of 
the 
following 
signs or symptoms developing 
during, 
or shortly 
after, 
caffeine 
use: 
1. 
Restlessness. 
2. 
Nervousness. 
3. 
Excitement. 
4. 
Insomnia. 
5. 
Flushed 
face. 
6. 
Diuresis. 
7. 
Gastrointestinal disturbance. 
8. 
Muscle 
twitching. 
9. 
Rambling 
flow of 
thought 
and 
speech. 
10. 
Tachycardia 
or cardiac arrhythmia. 
11. 
Periods of 
inexhaustibility. 
12. 
Psychomotor agitation. 

C. 
The 
signs or symptoms in 
Criterion 
B 
cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
D. 
The 
signs or symptoms are 
not 
attributable 
to 
another medical condition 
and 
are 
not 
better explained 
by another mental disorder, 
including 
intoxication 
with 
another substance. 
Diagnostic Features 


Caffeine can be consumed from 
a number of different 
sources, including coffee, tea, caffeinated 
soda,  energy  drinks, over-the-counter analgesics and cold remedies, weight-loss aids, and 
chocolate. Caffeine is also increasingly being used as an additive to vitamins and to food 
products. More than 85% of children and adults in the United States consume caffeine. Some 
caffeine users display symptoms consistent 
with problematic use, including tolerance and 
withdrawal 
(see  Caffeine Withdrawal  later in this chapter); 
the data are not 
available at 
this 
time to determine the clinical 
significance of a caffeine use disorder and its prevalence. In 
contrast, there is evidence that 
caffeine withdrawal 
and caffeine intoxication are clinically 
significant and sufficiently prevalent. 


The essential 
feature of caffeine intoxication is recent 
consumption of caffeine and five or 
more signs or symptoms that 
develop during or shortly after caffeine use (Criteria A and B). 
Symptoms include restlessness, nervousness, excitement, insomnia, flushed face, diuresis, and 
gastrointestinal complaints, which can occur with low doses (e.g., 200 mg) in 


570 


vulnerable individuals such as children, the elderly, or individuals who have not 
been 
exposed to caffeine previously. Symptoms that 
generally appear at 
levels of more than 1 g/day 
include muscle twitching, rambling flow of thought 
and speech, tachycardia or cardiac 
arrhythmia, periods of inexhaustibility, and psychomotor agitation. Caffeine intoxication may 
not 
occur despite high caffeine intake because of the development 
of tolerance. The signs or 
symptoms must 
cause clinically significant 
distress or impairment 
in social, occupational, or 
other important 
areas of functioning (Criterion C). The signs or symptoms must 
not 
be 
attributable to another medical 
condition and are not 
better explained by another mental 
disorder 
(e.g., an anxiety disorder) or intoxication with another substance (Criterion D). 


Associated Features 


Mild sensory disturbances (e.g., ringing in the ears and flashes of light) may occur with high 
doses of caffeine. Although large doses of caffeine can increase heart 
rate, typical 
dietary doses 
can slow heart 
rate. Whether excess caffeine intake can cause headaches is unclear. On physical 
examination, agitation, restlessness, sweating, tachycardia, flushed face, and increased bowel 
motility may be seen. Caffeine blood levels may provide important 
information for diagnosis, 
particularly when the individual 
is a poor historian, although these levels are not 
diagnostic by 
themselves in view of the individual variation in response to caffeine. 


Prevalence 



The prevalence of caffeine intoxication in the general 
population is unclear. In the United States, 
approximately 7% of individuals in the population may experience five or more symptoms along 
with functional impairment consistent with a diagnosis of caffeine intoxication. 


Consumption of caffeinated energy drinks, often together with alcohol, leading to caffeine 
intoxication, has increased among adolescents and young adults in high-income countries, 
resulting in the doubling of U.S. emergency department 
visits related to caffeinated energy 
drinks between 2007 and 2011. 


Development and Course 


Consistent 
with a half-life of caffeine of approximately 4 6 hours, caffeine intoxication 
symptoms usually remit 
within the first 
day or so and do not 
have any known long-lasting 
consequences. However, individuals who consume very high doses of caffeine (i.e., 5 10 g) may 
require immediate medical attention, as such doses can be lethal. 


With advancing age, individuals are likely to demonstrate increasingly intense reactions to 
caffeine, with greater complaints of interference with sleep or feelings of hyperarousal. Caffeine 
intoxication among young individuals after consumption of highly caffeinated products, 
including energy drinks, has been observed. Children and adolescents may be at 
increased risk 
for caffeine intoxication because of low body weight, lack of tolerance, and lack of knowledge 
about the pharmacological effects of caffeine. 


Risk and Prognostic Factors 


Environmental. 
Caffeine intoxication is often seen among individuals who use caffeine less 
frequently or in those who have recently increased their caffeine intake by a substantial 
amount. 
Furthermore, oral 
contraceptives significantly decrease the elimination of caffeine and 
consequently may increase the risk of intoxication. 


Genetic 
and 
physiological. 
Genetic factors may affect risk of caffeine intoxication. 


571 


Functional 
Consequences of Caffeine Intoxication 


Impairment 
from 
caffeine intoxication may have serious consequences, including dysfunction at 
work or school, social 
indiscretions, or failure to fulfill 
role obligations. Moreover, extremely 
high doses of caffeine can be fatal. In some cases, caffeine intoxication may precipitate a 
caffeine-induced disorder. 


Differential 
Diagnosis 


Independent 
mental 
disorders. 
Caffeine intoxication may be characterized by symptoms (e.g., 
panic attacks) that 
resemble independent 
mental 
disorders. To meet 
criteria for caffeine 
intoxication, the symptoms must 
not 
be associated with another medical 
condition or another 
mental 
disorder, such as an anxiety disorder, that 
could better explain them. Manic episodes; 
panic disorder; 
generalized anxiety disorder; 
amphetamine intoxication; 
sedative, hypnotic, or 
anxiolytic withdrawal 
or tobacco withdrawal; 
sleep disorders; 
and medication-induced side 
effects (e.g., akathisia) can cause a clinical picture that is similar to that of caffeine intoxication. 



Caffeine-induced 
mental 
disorders. 
The temporal 
relationship of the symptoms to increased 
caffeine use or to abstinence from 
caffeine helps to establish the diagnosis. Caffeine intoxication 
is differentiated from 
caffeine-induced anxiety disorder, with onset 
during intoxication (see 
 Substance/Medication-Induced Anxiety Disorder  in the chapter  Anxiety Disorders ), and 
caffeine-induced sleep disorder, with onset 
during intoxication (see  Substance/Medication-
Induced Sleep Disorder  in the chapter  Sleep-Wake Disorders ), because the symptoms (e.g., 
anxiety and insomnia, respectively) in these latter disorders are in excess of those usually 
associated with caffeine intoxication, predominate in the clinical 
presentation, and are severe 
enough to warrant independent clinical attention. 


Comorbidity 


Typical 
dietary doses of caffeine have not 
been consistently associated with medical 
problems. 
However, heavy use (e.g., > 400 mg) can cause or exacerbate anxiety and somatic symptoms and 
gastrointestinal 
distress. With acute, extremely high doses of caffeine, grand mal 
seizures and 
respiratory failure may result 
in death. Excessive caffeine use is associated with depressive 
disorders, bipolar disorders, eating disorders, psychotic disorders, sleep disorders, and substance-
related disorders, whereas individuals with anxiety disorders are more likely to avoid caffeine. 


Caffeine Withdrawal 


Diagnostic Criteria 
F15.93 


A. 
Prolonged 
daily use 
of 
caffeine. 
B. 
Abrupt 
cessation 
of 
or reduction 
in 
caffeine 
use, 
followed 
within 
24 
hours by 
three 
(or more) of 
the 
following 
signs or symptoms: 
1. 
Headache. 
2. 
Marked 
fatigue 
or drowsiness. 
3. 
Dysphoric mood, 
depressed 
mood, 
or irritability. 
4. 
Difficulty concentrating. 
5. 
Flu-like 
symptoms (nausea, 
vomiting, 
or muscle 
pain/stiffness). 
572 


C. 
The 
signs or symptoms in 
Criterion 
B 
cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
D. 
The 
signs or symptoms are 
not 
associated 
with 
the 
physiological effects of 
another medical condition 
(e.g., 
migraine, 
viral illness) and 
are 
not 
better 
explained 
by another mental disorder, 
including 
intoxication 
or withdrawal from 
another substance. 

Diagnostic Features 


The essential 
feature of caffeine withdrawal 
is the presence of a characteristic withdrawal 
syndrome that 
develops after the abrupt 
cessation of (or substantial 
reduction in) prolonged daily 
caffeine ingestion (Criterion B). Because individuals may be unaware of the wide array of 
sources of caffeine beyond coffee, colas, and energy drinks (e.g., over-the-counter analgesics and 
cold remedies, weight 
loss aids, chocolate), they may not 
connect 
ingestion of these substances 
with symptoms of caffeine withdrawal. The caffeine withdrawal 
syndrome is indicated by three 
or more of the following (Criterion B): 
headache; 
marked fatigue or drowsiness; 
dysphoric 
mood, depressed mood, or irritability; 
difficulty concentrating; 
and flu-like symptoms (nausea, 
vomiting, or muscle pain/stiffness). The withdrawal 
syndrome causes clinically significant 
distress or impairment 
in social, occupational, or other important 
areas of functioning (Criterion 
C). The symptoms must 
not 
be associated with the physiological 
effects of another medical 
condition and are not better explained by another mental disorder (Criterion D). 


Headache is the hallmark feature of caffeine withdrawal 
and may be diffuse, gradual 
in 
development, throbbing, severe, and sensitive to movement. However, other symptoms of 
caffeine withdrawal 
can occur in the absence of headache. Caffeine is the most 
widely used 
behaviorally active drug in the world and is present 
in many different 
types of beverages (e.g., 
coffee, tea, mate, soft 
drinks, energy drinks), foods, energy aids, medications, and dietary 
supplements. Because caffeine ingestion is often integrated into social 
customs and daily rituals 
(e.g., coffee break, tea time), some caffeine consumers may be unaware of their physical 
dependence on caffeine. Thus, caffeine withdrawal 
symptoms could be unexpected and 
misattributed to other causes (e.g., the flu, migraine). Furthermore, caffeine withdrawal 
symptoms may occur when individuals are required to abstain from 
foods and beverages prior to 
medical 
procedures or when a usual 
caffeine dose is missed because of a change in routine (e.g., 
during travel, weekends). 


The probability and severity of caffeine withdrawal 
generally increase as a function of usual 
daily caffeine dose. However, there is large variability among individuals and within individuals 
across different 
episodes in the incidence, severity, and time course of withdrawal 
symptoms. 
Caffeine withdrawal 
symptoms may occur after abrupt 
cessation of relatively low chronic daily 
doses of caffeine (i.e., 100 mg). 


Associated Features 


Caffeine abstinence has been shown to be associated with impaired behavioral 
and cognitive 
performance (e.g., sustained attention), as well 
as with increased total 
sleep time, sleep 
efficiency, and slow-wave sleep. Electroencephalographic studies have shown that 
caffeine 
withdrawal 
symptoms are significantly associated with increases in theta power and decreases in 
beta-2 power. Decreased motivation to work and decreased sociability have also been reported 
during caffeine withdrawal. Increased analgesic use during caffeine withdrawal 
has been 
documented. 


Prevalence 


More than 85% of adults and children in the United States regularly consume caffeine, with adult 
caffeine consumers ingesting about 
280 mg/day on average. The incidence and prevalence of the 



caffeine withdrawal 
syndrome in the general 
population are unclear. In the United States, 
headache may occur in approximately 50% of cases of caffeine abstinence. 


573 


In attempts to permanently stop caffeine use, more than 70% of individuals in a U.S. 
metropolitan county reported at 
least 
one caffeine withdrawal 
symptom 
(47% experienced 
headache), and 24% experienced headache plus one or more other symptoms as well 
as 
functional 
impairment 
due to withdrawal. Among individuals who abstained from 
caffeine for at 
least 
24 hours but 
were not 
trying to permanently stop caffeine use, 11% experienced headache 
plus one or more other symptoms as well 
as functional 
impairment. Caffeine consumers can 
decrease the incidence of caffeine withdrawal 
by using caffeine daily or only infrequently (e.g., 
no more than 2 consecutive days). Gradual 
reduction in caffeine over a period of days or weeks 
may decrease the incidence and severity of caffeine withdrawal. 


Development and Course 


Symptoms usually begin 12 24 hours after the last 
caffeine dose and peak after 1 2 days of 
abstinence. Caffeine withdrawal 
symptoms last 
for 2 9 days, with the possibility of withdrawal 
headaches occurring for up to 21 days. Symptoms usually remit 
rapidly (within 30 60 minutes) 
after re-ingestion of caffeine. Doses of caffeine significantly less than the individual s usual daily 
dose may be sufficient 
to prevent 
or attenuate caffeine withdrawal 
symptoms (e.g., consumption 
of 25 mg by an individual who typically consumes 300 mg). 


Caffeine is unique in that 
it 
is a behaviorally active drug that 
is consumed by individuals of 
nearly all 
ages, with rates of caffeine consumption and overall 
level 
of caffeine consumption 
increasing with age. Although caffeine withdrawal 
among children and adolescents has been 
documented, relatively little is known about 
risk factors for caffeine withdrawal 
among this age 
group. The use of highly caffeinated energy drinks is increasing in young people, which could 
increase the risk for caffeine withdrawal. 


Risk and Prognostic Factors 


Temperamental. 
Heavy caffeine use has been observed among individuals with mental 
disorders, 
including eating disorders and alcohol 
and other substance use disorders, as well 
as among 
individuals who smoke cigarettes and those who are incarcerated. Thus, these individuals could 
be at higher risk for caffeine withdrawal upon acute caffeine abstinence. 


Environmental. 
The unavailability of caffeine is an environmental 
risk factor for incipient 
withdrawal 
symptoms. While caffeine is legal 
and usually widely available, there are conditions 
in which caffeine use may be restricted, such as during medical 
procedures, pregnancy, 
hospitalizations, religious observances, wartime, travel, and research participation. These 
external 
environmental 
circumstances may precipitate a withdrawal 
syndrome in vulnerable 
individuals. 


Genetic 
and 
physiological. 
Genetic factors appear to increase vulnerability to caffeine withdrawal, 
but no specific genes have been identified. 


Culture-Related Diagnostic Issues 



Habitual 
caffeine consumers who fast 
for religious reasons may be at 
increased risk for caffeine 
withdrawal. 


Sex- and Gender-Related Diagnostic Issues 


Metabolism 
of caffeine is slower in females who use oral 
contraceptives and in the luteal 
phase 
of the menstrual 
cycle, and caffeine metabolism 
becomes progressively slower in the second and 
third trimesters of pregnancy compared with the first 
trimester and the nonpregnant 
state. These 
features reduce the rate of clearance and may diminish withdrawal, although they can also 
lengthen the duration of caffeine-associated adverse symptoms. It 
is unlikely that 
doses < 300 
mg/day are associated with adverse reproductive outcomes in pregnancy. 


574 


Functional 
Consequences of Caffeine Withdrawal 


Caffeine withdrawal 
symptoms can vary from 
mild to extreme, at 
times causing functional 
impairment 
in normal 
daily activities. Rates of functional 
impairment 
in studies conducted 
largely in the United States range from 
10% to 55% (median 13%), with rates as high as 73% 
found among individuals who also show other problematic features of caffeine use. Examples of 
functional 
impairment 
include being unable to work, exercise, or care for children; 
staying in bed 
all 
day; 
missing religious services; 
ending a vacation early; 
and canceling a social 
gathering. 
Caffeine withdrawal 
headaches may be described by individuals as  the worst 
headaches  ever 
experienced. Decrements in cognitive and motor performance have also been observed. 


Differential 
Diagnosis 


Other medical 
conditions 
and 
medication 
side 
effects. 
Caffeine withdrawal 
can mimic migraine and 
other headache disorders, viral 
illnesses, sinus conditions, tension, other drug withdrawal 
states 
(e.g., from 
amphetamines, cocaine), and medication side effects. The final 
determination of 
caffeine withdrawal 
should rest 
on a determination of the pattern and amount 
consumed, the time 
interval 
between caffeine abstinence and onset 
of symptoms, and the particular clinical 
features 


presented by the individual. A challenge dose of caffeine followed by symptom 
remission may 
be used to confirm the diagnosis. 
Caffeine-induced 
sleep 
disorder. 
Caffeine withdrawal 
is distinguished from 
caffeine-induced sleep 


disorder (e.g., caffeine-induced sleep disorder, insomnia type, with onset 
during withdrawal) 
because the sleep symptoms are in excess of those usually associated caffeine withdrawal, 
predominate in the clinical presentation, and are severe enough to warrant clinical attention. 


Comorbidity 


Caffeine withdrawal 
may be associated with major depressive disorder, generalized anxiety 
disorder, panic disorder, antisocial 
personality disorder, moderate to severe alcohol 
use disorder, 
and cannabis and cocaine use. 


Caffeine-Induced 
Mental 
Disorders 



The following caffeine-induced mental 
disorders are described in other chapters of the manual 
with disorders with which they share phenomenology (see the substance/medication-induced 
mental 
disorders in these chapters): 
caffeine-induced anxiety disorder ( Anxiety Disorders ) and 
caffeine-induced sleep disorder ( Sleep-Wake Disorders ). These caffeine-induced mental 
disorders are diagnosed instead of caffeine intoxication or caffeine withdrawal 
only when the 
symptoms are sufficiently severe to warrant independent clinical attention. 


Unspecified 
Caffeine-Related 
Disorder 


F15.99 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
caffeine-related 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any specific caffeine-related 
disorder or any of 
the 
disorders 
in 
the 
substance-related 
and 
addictive 
disorders diagnostic class. 


575 


Cannabis-Related Disorders 


Cannabis Use 
Disorder 
Cannabis Intoxication 
Cannabis Withdrawal 
Cannabis-Induced 
Mental Disorders 
Unspecified 
Cannabis-Related 
Disorder 


Cannabis Use Disorder 


Diagnostic Criteria 


A. 
A 
problematic pattern 
of 
cannabis use 
leading 
to 
clinically significant 
impairment 
or distress, 
as manifested 
by at 
least 
two 
of 
the 
following, 
occurring 
within 
a 
12month 
period: 
1. 
Cannabis is often 
taken 
in 
larger amounts or over a 
longer period 
than 
was 
intended. 
2. 
There 
is a 
persistent 
desire 
or unsuccessful efforts to 
cut 
down 
or control 
cannabis use. 

3. 
A 
great 
deal of 
time 
is spent 
in 
activities necessary to 
obtain 
cannabis, 
use 
cannabis, 
or recover from its effects. 
4. 
Craving, 
or a 
strong 
desire 
or urge 
to 
use 
cannabis. 
5. 
Recurrent 
cannabis use 
resulting 
in 
a 
failure 
to 
fulfill major role 
obligations at 
work, 
school, 
or home. 
6. 
Continued 
cannabis use 
despite 
having 
persistent 
or recurrent 
social or 
interpersonal problems caused 
or exacerbated 
by the 
effects of 
cannabis. 
7. 
Important 
social, 
occupational, 
or recreational activities are 
given 
up 
or 
reduced 
because 
of 
cannabis use. 
8. 
Recurrent 
cannabis use 
in 
situations in 
which 
it 
is physically hazardous. 
9. 
Cannabis use 
is continued 
despite 
knowledge 
of 
having 
a 
persistent 
or 
recurrent 
physical or psychological problem that 
is likely to 
have 
been 
caused 
or exacerbated 
by cannabis. 
10. 
Tolerance, 
as defined 
by either of 
the 
following: 
a. 
A 
need 
for markedly increased 
amounts of 
cannabis to 
achieve 
intoxication 
or desired 
effect. 
b. 
Markedly diminished 
effect 
with 
continued 
use 
of 
the 
same 
amount 
of 
cannabis. 
11. 
Withdrawal, 
as manifested 
by either of 
the 
following: 
a. 
The 
characteristic withdrawal syndrome 
for cannabis (refer to 
Criteria 
A 
and 
B 
of 
the 
criteria 
set 
for cannabis withdrawal). 
b. 
Cannabis (or a 
closely related 
substance) is taken 
to 
relieve 
or avoid 
withdrawal symptoms. 
Specify 
if: 
In 
early 
remission: 
After full criteria 
for cannabis use 
disorder were 
previously 
met, 
none 
of 
the 
criteria 
for cannabis use 
disorder have 
been 
met 
for at 
least 
3 
months but 


576 


for less than 
12 
months (with 
the 
exception 
that 
Criterion 
A4, 
 Craving, 
or a 


strong 
desire 
or urge 
to 
use 
cannabis,  may be 
met). 
In 
sustained 
remission: 
After full criteria 
for cannabis use 
disorder were 
previously met, 
none 
of 
the 
criteria 
for cannabis use 
disorder have 
been 
met 
at 
any time 
during 
a 
period 
of 
12 
months or longer (with 
the 
exception 
that 
Criterion 
A4, 
 Craving, 
or a 
strong 
desire 
or urge 
to 
use 
cannabis,  may be 
present). 


Specify 
if: 
In 
a 
controlled 
environment: 
This additional specifier is used 
if 
the 
individual is 
in 
an 
environment 
where 
access to 
cannabis is restricted. 
Code 
based 
on 
current severity/remission: 
If 
a 
cannabis intoxication, 
cannabis 
withdrawal, 
or another cannabis-induced 
mental disorder is also 
present, 
do 
not 
use 



the 
codes below for cannabis use 
disorder. 
Instead, 
the 
comorbid 
cannabis use 
disorder is indicated 
in 
the 
4th 
character of 
the 
cannabis-induced 
disorder code 
(see 
the 
coding 
note 
for cannabis intoxication, 
cannabis withdrawal, 
or a 
specific 
cannabis-induced 
mental disorder). 
For example, 
if 
there 
is comorbid 
cannabis-
induced 
anxiety disorder and 
cannabis use 
disorder, 
only the 
cannabis-induced 
anxiety disorder code 
is given, 
with 
the 
4th 
character indicating 
whether the 
comorbid 
cannabis use 
disorder is mild, 
moderate, 
or severe: 
F12.180 
for mild 
cannabis use 
disorder with 
cannabis-induced 
anxiety disorder or F12.280 
for a 
moderate 
or severe 
cannabis use 
disorder with 
cannabis-induced 
anxiety disorder. 


Specify 
current 
severity/remission: 


F12.10 
Mild: 
Presence 
of 
2 3 
symptoms. 


F12.11 
Mild, 
In 
early 
remission 


F12.11 
Mild, 
In 
sustained 
remission 


F12.20 
Moderate: 
Presence 
of 
4 5 
symptoms. 


F12.21 
Moderate, 
In 
early 
remission 


F12.21 
Moderate, 
In 
sustained 
remission 


F12.20 
Severe: 
Presence 
of 
6 
or more 
symptoms. 


F12.21 
Severe, 
In 
early 
remission 


F12.21 
Severe, 
In 
sustained 
remission 


Specifiers 


 In a controlled environment  applies as a further specifier of remission if the individual 
is both 
in remission and in a controlled environment 
(i.e., in early remission in a controlled environment 
or in sustained remission in a controlled environment). Examples of these environments are 
closely supervised and substance-free jails, therapeutic communities, and locked hospital units. 


Changing severity across time in an individual 
may also be reflected by changes in the 
frequency (e.g., days of use per month or times used per day) and/or dose (e.g., amount 
used per 
episode) of cannabis, as assessed by individual 
self-report, report 
of knowledgeable others, 
clinician s observations, and biological testing. 


Diagnostic Features 


Cannabis use disorder includes problems associated with use of substances derived from 
the 
cannabis plant 
and chemically similar synthetic compounds. In these substances, the primary 
component 
with psychoactive effects (and hence, addiction potential) is the cannabinoid delta-9tetrahydrocannabinol 
(delta-9-THC 
or THC). Cannabinoids have diverse effects in the brain, 
prominent among which are actions on CB1 and CB2 
cannabinoid receptors found throughout 
the 


central nervous system. 


577 


Cannabis is used in many forms. It 
is most 
commonly smoked in a cigarette-like form 
(often 



called  joints  or  reefers ), and also in pipes, water pipes (bongs or hookahs), or hollowed-out 
cigars ( blunts ). More recently developed methods include  vaping  (vaporizing) by heating 
without 
combustion plant 
cannabis material 
to release psychoactive components for inhalation, 
and  dabbing,  in which a concentrated cannabis product 
(butane hash oil, known as  dabs ), 
created through butane extraction of THC 
from 
cannabis plant 
material, is heated and inhaled. 
Vaping and dabbing are gaining popularity, particularly among youth. Cannabis can also be 
ingested orally in food (edibles) or beverages. Inhalation typically produces more rapid and 
intense onset 
of effects than oral 
administration. Hashish or hash oil, a concentrated extraction of 
the cannabis plant, is also used. Across products, cannabis potency (THC 
concentration) varies 
greatly, averaging 10% 15% in typical 
cannabis plant 
material, 30% 40% in hashish, and 50%  
55% in hash oil. During the past 
two decades, the potency of seized illegal 
plant 
cannabis has 
steadily increased, and legal 
cannabis products may have even higher THC 
potency (e.g., 20% 
for plant 
material 
and 68% for cannabis extracts). Synthetic oral 
THC 
formulations 
(pill/capsules/sprays) are also available for various medical 
uses (e.g., chronic pain; 
nausea and 
vomiting caused by chemotherapy or ano-rexia; 
weight 
loss among those with AIDS). Other 
entirely illicit 
synthetic cannabinoid compounds (e.g., K2, Spice, JWH-018, JWH-073) are in the 
form 
of plant 
material 
sprayed with a cannabinoid formulation. Although such synthetic 
cannabinoids are designed to mimic cannabis effects, their chemical 
composition, potency, 
effects, and duration of action are unpredictable, and they may cause more severe adverse effects 
than cannabis plant products, including seizures, cardiac conditions, psychosis, and even death. 


In the United States, cannabis remains an illegal 
substance under federal 
law, while the legal 
status of cannabis varies by state. Thus, cannabis use under state law can involve an illicit 
product, a product 
authorized for medical 
purposes, or a completely legal 
product. The most 
common medical 
purpose for cannabis use is chronic pain, and the conditions approved for 
medicinal 
cannabis use vary from 
state to state. When cannabis or a cannabinoid is taken as 
indicated for a medical 
condition, tolerance and withdrawal 
(physiological 
dependence) may 
occur but 
should not 
be the primary basis for diagnosing cannabis use disorder. The efficacy of 
cannabis for different 
medical 
conditions continues to be debated, and cannabis use as medically 
advised should be taken into account when a cannabis use disorder diagnosis is being considered. 


Patterns of cannabis use can range from 
light, infrequent 
use to heavy, frequent 
use. 
Individuals with DSM-5 cannabis use disorder use cannabis frequently (on average, 4 or more 
days a week), and some individuals may use cannabis throughout 
the day over a period of 
months or years. Because of the increasingly common perception that 
cannabis use is harmless, 
individuals may not 
recognize that 
symptoms of cannabis use disorder (e.g., withdrawal 
symptoms) are cannabis related. Additionally, among individuals with multiple substance use 
disorders, lack of clarity about 
whether symptoms are caused by cannabis or by other substances 
may lead to underreporting of cannabis use disorder symptoms. 


Cannabis use disorder is defined by the same 11 criteria that 
define the other substance use 
disorders, as supported by considerable empirical 
evidence. These criteria, a cluster of behavioral 
and physical 
symptoms, lead to clinically significant 
impairment 
or distress and can include 
withdrawal, tolerance, craving, spending a great deal of time in activities related to the substance, 
and hazardous use (e.g., driving while under its influence). Some individuals who use cannabis 
multiple times per day do not 
perceive themselves as spending excessive time under the 
influence of cannabis or recovering from 
its effects, despite being intoxicated from 
cannabis or 
coming down from 
its effects most 
of the time, most 
days. An important 
marker of a severe 



cannabis use disorder is continued use despite negative effects on other important 
activities or 
relationships (e.g., school, work, sports, partner or parent relationship). 


578 


Regular cannabis users become tolerant 
to many acute cannabis effects, and cessation of 
regular cannabis use generally leads to a cannabis withdrawal 
syndrome. Cannabis withdrawal 
can cause significant 
distress, leading to continued use to relieve the symptoms and difficulty 
quitting use or relapse. 


Associated Features 


Individuals who regularly use cannabis often report 
using it 
to cope with mood, insomnia, anger, 
pain, or other physiological 
or psychological 
problems, and individuals diagnosed with cannabis 
use disorder frequently have other concurrent 
mental 
disorders. Careful 
assessment 
can reveal 
that 
cannabis use contributes to exacerbation of these symptoms, as well 
as other reasons for 
frequent 
use (e.g., the coping motives listed above; 
to experience euphoria; 
as an enjoyable 
social 
activity). Chronic intake of cannabis can produce a lack of motivation that 
resembles 
persistent depressive disorder. 


Because some individuals may underreport 
the amount 
or frequency of their cannabis use, 
provider awareness of common signs and symptoms of cannabis use and intoxication facilitates 
better assessment 
of cannabis use disorder. Some additional 
signs of acute and chronic use are 
red eyes (conjunctival 
injection), cannabis odor on clothing, yellowing of fingertips (from 
smoking joints), chronic cough, burning of incense (to hide the odor), and exaggerated craving 
and impulse for specific foods, sometimes at odd times of the day or night. 


Prevalence 


Cannabinoids, especially cannabis, are the most 
widely used illicit 
psychoactive substances in 
the United States. The following prevalence data are drawn from 
U.S.-based studies, unless 
otherwise noted. Among youth (ages 12 17 years), the past-year prevalence of DSM-IV 
cannabis use disorder is 2.7% 3.1%. Among adults age 18 years and older, the prevalence is 
1.5% 2.9%. Among cannabis users, the prevalence of DSM-IV cannabis use disorder is 20.4% 
among youth and 30.6% among adults. For DSM-5 cannabis use disorder, 12-month prevalence 
is approximately 2.5% among adults (1.4%, 0.6%, and 0.6% at 
mild, moderate, and severe 
levels, respectively). During the past 
decade, the prevalence of cannabis use disorder has 
decreased among adolescents. In contrast, among adults, some studies suggest 
that 
the 
prevalence of cannabis use disorder has either remained stable or increased for example, 
among adults in the general 
population, patients in inpatient 
settings, and patients in the Veterans 
Health Administration. Globally, the age-standardized rate of cannabis use disorders was 289.7 
per 100,000 people in 2016, a 25.6% increase over 1990. Prevalence varies widely across 
geographic regions, being lowest in Western Sub-Saharan Africa and highest in North America. 


According to age, the prevalence of cannabis use disorder in the United States is highest 
among individuals ages 18 29 years (6.9%) and lowest 
among individuals age 45 years and 
older (0.8%). Rates of cannabis use disorder are greater in men than in women (3.5% vs. 1.7%) 
and in boys than in girls ages 12 17 years (3.4% vs. 2.8%), although gender differences have 



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667 



Neurocognitive Disorders 


The neurocognitive disorders 
(NCDs) begin with delirium, followed by the 
syndromes of major NCD, mild NCD, and their etiological 
subtypes. The major or mild NCD 
subtypes are NCD due to Alzheimer s disease; vascular NCD; NCD with Lewy bodies; NCD due 
to Parkinson s disease; 
frontotemporal 
NCD; 
NCD due to traumatic brain injury; 
NCD due to 
HIV infection; 
substance/medication-induced NCD; 
NCD due to Huntington s disease; 
NCD due 
to prion disease; 
NCD due to another medical 
condition; 
NCD due to multiple etiologies; 
and 
unspecified NCD. The NCD category encompasses the group of disorders in which the primary 
clinical 
deficit 
is in cognitive function, and that 
are acquired rather than developmental. 
Although cognitive deficits are present 
in many if not 
all 
mental 
disorders (e.g., schizophrenia, 
bipolar disorders), only disorders whose core features are cognitive are included in the NCD 
category. The NCDs are those in which impaired cognition has not 
been present 
since birth or 
very early life, and thus represents a decline from a previously attained level of functioning. 


The NCDs are unique among DSM-5 categories in that 
these are syndromes for which the 
underlying pathology, and frequently the etiology as well, can potentially be determined. The 
various underlying disease entities have all 
been the subject 
of extensive research, clinical 
experience, and expert 
consensus on diagnostic criteria. The DSM-5 criteria for these disorders 
have been developed in close consultation with the expert 
groups for each of the disease entities 
and align as closely as possible with the current 
consensus criteria for each of them. The 
potential 
utility of biomarkers is also discussed in relation to diagnosis. Dementia is subsumed 
under the newly named entity major neurocognitive disorder, although the term 
dementia 
is not 
precluded from 
use in the etiological 
subtypes in which that 
term 
is standard. Furthermore, 
DSM-5 recognizes a less severe level 
of cognitive impairment, mild neurocognitive disorder, 
which can also be a focus of care. Diagnostic criteria are provided for both these syndromic 
entities, followed by diagnostic criteria for the different 
etiological 
subtypes. Several 
of the 
NCDs frequently coexist 
with one another, and their relationships may be multiply characterized 
under different 
chapter subheadings, including  Differential 
Diagnosis  (e.g., NCD due to 
Alzheimer s disease vs. vascular NCD),  Risk and Prognostic Factors  (e.g., vascular pathology 
increasing the clinical 
expression of Alzheimer s disease), or  Comorbidity  (e.g., mixed 
Alzheimer s disease vascular pathology). 


The term 
dementia 
is retained in DSM-5 for continuity and may be used in settings where 
physicians and patients are accustomed to this term. Although dementia is the customary term 
for disorders like the degenerative dementias that 
usually affect 
older adults, the term 
neurocognitive disorder 
is widely used and often preferred for conditions affecting younger 
individuals, such as impairment 
secondary to traumatic brain injury or HIV infection. 
Furthermore, the major NCD definition is somewhat 
broader than the term 
dementia, 
in that 
a 
diagnosis of major NCD can be made if there is a significant 
cognitive decline in only one 
cognitive domain, whereas a diagnosis of dementia in ICD-10 and ICD-11 (and formerly in 



DSM-IV) requires multiple cognitive deficits. Thus, cases that 
would qualify in ICD-10 and 
ICD-11 (and formerly DSM-IV) for a diagnosis of amnestic disorder (memory impairment 
in the 
absence of other cognitive deficits) are diagnosed as major NCD in DSM-5. 


668 


Neurocognitive Domains 


The criteria for the various NCDs are based on defined cognitive domains. Table 1 
provides for 
each of the key domains a working definition, examples of symptoms or observations regarding 
impairments in everyday activities, and examples of assessments. The domains thus defined, 
along with guidelines for clinical 
thresholds, form 
the basis on which the NCDs, their levels, and 
their subtypes may be diagnosed. 


669 


TABLE 
1 
Neurocognitive 
domains 


Cognitive 
domain 
Examples 
of 
symptoms 
or observations 
Examples 
of 
assessments 
Complex attention 
Major: Has increased difficulty in environments 
Sustained attention: Maintenance of attention 
(sustained attention, 
with multiple stimuli (TV, radio, conversation); 
over time (e.g., pressing a button every time a 
divided attention, 
is easily distracted by competing events in the 
tone is heard, and over a period of time). 
selective attention, 
processing speed) 
environment. Is unable to attend unless input is 
restricted and simplified. Has difficulty holding 
new information in mind, such as recalling 
phone numbers or addresses just given, or 
reporting what was just said. Is unable to 
Selective attention: Maintenance of attention 
despite competing stimuli or distractors: 
hearing numbers and letters read and asked to 
count only letters. 
perform mental calculations. All thinking takes 
longer than usual, and components to be 
processed must be simplified to one or a few. 
Mild: Normal tasks take longer than previously. 
Begins to find errors in routine tasks; finds 
work needs more double-checking than 
previously. Thinking is easier when not 
competing with other things (radio, TV, other 
Divided attention: Attending to two tasks within 
the same time period: rapidly tapping while 
learning a story being read. Processing speed 
can be quantified on any task by timing it (e.g., 
time to put together a design of blocks; time to 
match symbols with numbers; speed in 
responding, such as counting speed or serial 3 
speed). 
conversations, cell phone, driving). 
Executive function 
Major: Abandons complex projects. Needs to 
Planning: Ability to find the exit to a maze; 
(planning, decision-focus on one task at a time. Needs to rely on 
interpret a sequential picture or object 
making, working 
others to plan instrumental activities of daily 
arrangement. 
memory, responding 
to feedback/error 
correction, overriding 
habits/inhibition, 
mental flexibility) 
living or make decisions. 
Mild: Increased effort required to complete 
multistage projects. Has increased difficulty 
multitasking or difficulty resuming a task 
interrupted by a visitor or phone call. May 
complain of increased fatigue from the extra 
effort required to organize, plan, and make 
decisions. May report that large social 
gatherings are more taxing or less enjoyable 
Decision-making: Performance of tasks that 
assess process of deciding in the face of 
competing alternatives (e.g., simulated 
gambling). 
Working memory: Ability to hold information for 
a brief period and to manipulate it (e.g., adding 
up a list of numbers or repeating a series of 
numbers or words backward). 
because of increased effort required to follow 
shifting conversations. 
Feedback/error utilization: Ability to benefit 
from feedback to infer the rules for solving a 
problem. 
Overriding habits/inhibition: Ability to choose a 
more complex and effortful solution to be 
correct (e.g., looking away from the direction 
indicated by an arrow; naming the color of a 
word s font rather than naming the word). 



word s font rather than naming the word). 
Mental/cognitive flexibility: Ability to shift 
between two concepts, tasks, or response rules 
(e.g., from number to letter, from verbal to key-
press response, from adding numbers to 
ordering numbers, from ordering objects by size 
to ordering by color). 
670 
Major: Repeats self in conversation, often within 
the same conversation. Cannot keep track of 
Immediate memory span: Ability to repeat a list 
of words or digits. Note: Immediate memory 
Learning and memory 
(immediate memory, 
recent memory 
short list of items when shopping or of plans 
for the day. Requires frequent reminders to 
orient to task at hand. 
sometimes subsumed under  working memory  
(see  Executive Function ). 
Recent memory: Assesses the process of encoding 
[including free recall, 
Mild: Has difficulty recalling recent events, and 
new information (e.g., word lists, a short story, 
cued recall, and 
relies increasingly on list making or calendar. 
or diagrams). The aspects of recent memory 
recognition memory], 
Needs occasional reminders or re-reading to 
that can be tested include 1) free recall (the 
very-long-term 
keep track of characters in a movie or novel. 
individual is asked to recall as many words, 
memory [semantic; 
Occasionally may repeat self over a few weeks 
diagrams, or elements of a story as possible); 
autobiographical], 
to the same person. Loses track of whether bills 
2) cued recall (examiner aids recall by 
implicit learning) 
have already been paid. 
Note: Except in severe forms of major 
neurocognitive disorder, semantic, 
autobiographical, and implicit learning are 
relatively preserved, compared with recent 
memory. 
providing semantic cues such as  List all the 
food items on the list  or  Name all of the 
children from the story ); and 3) recognition 
memory (examiner asks about specific items  
e.g.,  Was  apple  on the list?  or  Did you see 
this diagram or figure? ). Other aspects of 
memory that can be assessed include semantic 
memory (memory for facts), autobiographical 
memory (memory for personal events or 
people), and implicit (procedural) learning 
(unconscious learning of skills). 
Language (expressive 
Major: Has significant difficulties with 
Expressive language: Confrontational naming 
language [including 
expressive or receptive language. Often uses 
(identification of objects or pictures); fluency 
naming, word 
general-use phrases such as  that thing  and 
(e.g., name as many items as possible in a 
finding, fluency, and 
 you know what I mean,  and prefers general 
semantic [e.g., animals] or phonemic [e.g., 
grammar, and syntax] 
pronouns rather than names. With severe 
words starting with  f ] category in 1 minute). 
and receptive 
language) 
impairment, may not even recall names of 
closer friends and family. Idiosyncratic word 
usage, grammatical errors, and spontaneity of 
output and economy of utterances occur. 
Stereotypy of speech occurs; echolalia and 
automatic speech typically precede mutism. 
Grammar and syntax (e.g., omission or incorrect 
use of articles, prepositions, auxiliary verbs): 
Errors observed during naming and fluency 
tests are compared with norms to assess 
frequency of errors and compare with normal 
slips of the tongue. 
Mild: Has noticeable word-finding difficulty. 
May substitute general for specific terms. May 
avoid use of specific names of acquaintances. 
Grammatical errors involve subtle omission or 
incorrect use of articles, prepositions, auxiliary 
verbs, etc. 
Receptive language: Comprehension (word 
definition and object-pointing tasks involving 
animate and inanimate stimuli): performance of 
actions/activities according to verbal command. 
671 
Major: Has significant difficulties with 
Visual perception: Line bisection tasks can be 
Perceptual-motor 
previously familiar activities (using tools, 
used to detect basic visual defect or attentional 
(includes abilities 
driving motor vehicle), navigating in familiar 
neglect. Motor-free perceptual tasks (including 
subsumed under the 
environments; is often more confused at dusk, 
facial recognition) require the identification 
terms visual 
when shadows and lowering levels of light 
and/or matching of figures best when tasks 
perception, 
visuoconstructional, 
perceptual-motor, 
praxis, and gnosis) 
change perceptions. 
Mild: May need to rely more on maps or others 
for directions. Uses notes and follows others to 
get to a new place. May find self lost or turned 
around when not concentrating on task. Is less 
cannot be verbally mediated (e.g., figures are 
not objects); some require the decision of 
whether a figure can be  real  or not based on 
dimensionality. 
Visuoconstructional: Assembly of items requiring 
precise in parking. Needs to expend greater 
effort for spatial tasks such as carpentry, 
assembly, sewing, or knitting. 
hand-eye coordination, such as drawing, 
copying, and block assembly. 



assembly, sewing, or knitting. 
Perceptual-motor: Integrating perception with 
purposeful movement (e.g., inserting blocks 
into a form board without visual cues; rapidly 
inserting pegs into a slotted board). 
Praxis: Integrity of learned movements, such as 
ability to imitate gestures (wave goodbye) or 
pantomime use of objects to command ( Show 
me how you would use a hammer ). 
Gnosis: Perceptual integrity of awareness and 
recognition, such as recognition of faces and 
colors. 
Social cognition 
Major: Behavior clearly out of acceptable social 
Recognition of emotions: Identification of 
(recognition of 
range; shows insensitivity to social standards of 
emotion in images of faces representing a 
emotions, theory of 
modesty in dress or of political, religious, or 
variety of both positive and negative emotions. 
mind) 
sexual topics of conversation. Focuses 
excessively on a topic despite group s 
disinterest or direct feedback. Behavioral 
intention without regard to family or friends. 
Makes decisions without regard to safety (e.g., 
inappropriate clothing for weather or social 
setting). Typically, has little insight into these 
changes. 
Theory of mind: Ability to consider another 
person s mental state (thoughts, desires, 
intentions) or experience story cards with 
questions to elicit information about the mental 
state of the individuals portrayed, such as 
 Where will the girl look for the lost bag?  or 
 Why is the boy sad?  
Mild: Has subtle changes in behavior or attitude, 
often described as a change in personality, such 
as less ability to recognize social cues or read 
facial expressions, decreased empathy, 
increased extraversion or introversion, 
decreased inhibition, or subtle or episodic 
apathy or restlessness. 


672 


Delirium 


Diagnostic Criteria 


A. 
A 
disturbance 
in 
attention 
(i.e., 
reduced 
ability to 
direct, 
focus, 
sustain, 
and 
shift 
attention) accompanied 
by reduced 
awareness of 
the 
environment. 
B. 
The 
disturbance 
develops over a 
short 
period 
of 
time 
(usually hours to 
a 
few 
days), 
represents a 
change 
from baseline 
attention 
and 
awareness, 
and 
tends to 
fluctuate 
in 
severity during 
the 
course 
of 
a 
day. 
C. 
An 
additional disturbance 
in 
cognition 
(e.g., 
memory deficit, 
disorientation, 
language, 
visuospatial ability, 
or perception). 
D. 
The 
disturbances in 
Criteria 
A 
and 
C are 
not 
better explained 
by another 
preexisting, 
established, 
or evolving 
neurocognitive 
disorder and 
do 
not 
occur in 
the 
context 
of 
a 
severely reduced 
level of 
arousal, 
such 
as coma. 
E. 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings 
that 
the 
disturbance 
is a 
direct 
physiological consequence 
of 
another medical 
condition, 
substance 
intoxication 
or withdrawal (i.e., 
due 
to 
a 
drug 
of 
abuse 
or to 
a 
medication), 
or exposure 
to 
a 
toxin, 
or is due 
to 
multiple 
etiologies. 

Specify 
if: 
Acute: 
Lasting 
a 
few hours or days. 
Persistent: 
Lasting 
weeks or months. 


Specify 
if: 
Hyperactive: 
The 
individual has a 
hyperactive 
level of 
psychomotor activity that 


may be 
accompanied 
by mood 
lability, 
agitation, 
and/or refusal to 
cooperate 
with 
medical care. 
Hypoactive: 
The 
individual has a 
hypoactive 
level of 
psychomotor activity that 


may be 
accompanied 
by sluggishness and 
lethargy that 
approaches stupor. 
Mixed 
level 
of activity: 
The 
individual has a 
normal level of 
psychomotor 
activity even 
though 
attention 
and 
awareness are 
disturbed. 
Also 
includes 
individuals whose 
activity level rapidly fluctuates. 
Specify 
whether: 
Substance 
intoxication 
delirium: 
This diagnosis should 
be 
made 
instead 
of 
substance 
intoxication 
when 
the 
symptoms in 
Criteria 
A 
and 
C predominate 
in 
the 
clinical picture 
and 
when 
they are 
sufficiently severe 
to 
warrant 
clinical 
attention. 
Coding 
note: 
The 
ICD-10-CM codes for the 
[specific substance] 
intoxication 
delirium are 
indicated 
in 
the 
table 
below. 
Note 
that 
the 
ICD-10-CM code 
depends on 
whether or not 
there 
is a 
comorbid 
substance 
use 
disorder 
present 
for the 
same 
class of 
substance. 
If 
a 
mild 
substance 
use 
disorder is 
comorbid 
with 
the 
substance 
intoxication 
delirium, 
the 
4th 
position 
character is 
 1,  and 
the 
clinician 
should 
record 
 mild 
[substance] 
use 
disorder  before 
the 
substance 
intoxication 
delirium (e.g., 
 mild 
cocaine 
use 
disorder with 
cocaine 
intoxication 
delirium ). 
If 
a 
moderate 
or severe 
substance 
use 
disorder is 
comorbid 
with 
the 
substance 
intoxication 
delirium, 
the 
4th 
position 
character is 
 2,  and 
the 
clinician 
should 
record 
 moderate 
[substance] 
use 
disorder  or 
 severe 
[substance] 
use 
disorder,  depending 
on 
the 
severity of 
the 
comorbid 
substance 
use 
disorder. 
If 
there 
is no 
comorbid 
substance 
use 
disorder (e.g., 
after a 
one-time 
heavy use 
of 
the 
substance), 
then 
the 
4th 
position 
character is 
 9,  and 
the 
clinician 
should 
record 
only the 
substance 
intoxication 
delirium. 


673 


ICD-10-CM 


With 
moderate 
or 
With 
mild 
use 
severe 
use 
Without 
use 
Substance 
intoxication 
delirium 
disorder 
disorder 
disorder 
Alcohol 
F10.121 
F10.221 
F10.921 
Cannabis 
F12.121 
F12.221 
F12.921 
Phencyclidine 
F16.121 
F16.221 
F16.921 
Other 
hallucinogen 
F16.121 
F16.221 
F16.921 



Inhalant 
F18.121 
F18.221 
F18.921 
Opioid 
F11.121 
F11.221 
F11.921 
Sedative, 
hypnotic, 
or 
anxiolytic 
F13.121 
F13.221 
F13.921 
Amphetamine-type 
substance 
(or 
other 
stimulant) 
F15.121 
F15.221 
F15.921 
Cocaine 
F14.121 
F14.221 
F14.921 
Other 
(or 
unknown) 
substance 
F19.121 
F19.221 
F19.921 


Substance 
withdrawal 
delirium: 
This diagnosis should 
be 
made 
instead 
of 
substance 
withdrawal when 
the 
symptoms in 
Criteria 
A 
and 
C predominate 
in 
the 
clinical picture 
and 
when 
they are 
sufficiently severe 
to 
warrant 
clinical attention. 


Coding 
note: 
The 
ICD-10-CM codes for the 
[specific substance] 
withdrawal 
delirium are 
indicated 
in 
the 
table 
below. 
Note 
that 
the 
ICD-10-CM code 
depends on 
whether or not 
there 
is a 
comorbid 
substance 
use 
disorder 
present 
for the 
same 
class of 
substance. 
If 
a 
mild 
substance 
use 
disorder is 
comorbid 
with 
the 
substance 
withdrawal delirium, 
the 
4th 
position 
character is 
 1,  and 
the 
clinician 
should 
record 
 mild 
[substance] 
use 
disorder  before 
the 
substance 
withdrawal delirium (e.g., 
 mild 
alcohol use 
disorder with 
alcohol 
withdrawal delirium ). 
If 
a 
moderate 
or severe 
substance 
use 
disorder is 
comorbid 
with 
the 
substance 
withdrawal delirium, 
the 
4th 
position 
character is 
 2,  and 
the 
clinician 
should 
record 
 moderate 
[substance] 
use 
disorder  or 
 severe 
[substance] 
use 
disorder,  depending 
on 
the 
severity of 
the 
comorbid 
substance 
use 
disorder. 
If 
there 
is no 
comorbid 
substance 
use 
disorder (e.g., 
after regular use 
of 
an 
anxiolytic substance 
taken 
as prescribed), 
then 
the 
4th 
position 
character is  9,  and 
the 
clinician 
should 
record 
only the 
substance 
withdrawal delirium. 


ICD-10-CM 


With 
moderate 
or 
With 
mild 
use 
severe 
use 
Without 
use 
Substance 
withdrawal 
delirium 
disorder 
disorder 
disorder 
Alcohol 
F10.131 
F10.231 
F10.931 
Opioid 
F11.188 
F11.288 
F11.988 
Sedative, 
hypnotic, 
or 
anxiolytic 
F13.131 
F13.231 
F13.931 
Other 
(or 
unknown) 
substance 
F19.131 
F19.231 
F19.931 


674 


Medication-induced 
delirium: 
This diagnosis applies when 
the 
symptoms in 


Criteria 
A 
and 
C arise 
as a 
side 
effect 
of 
a 
medication 
taken 
as prescribed. 
Code 
[specific medication] induced 
delirium: 
F11.921 
opioid 
taken 
as 
prescribed 
(or F11.988 
if 
during 
withdrawal from opioid 
taken 
as prescribed); 
F12.921 
pharmaceutical cannabis receptor agonist 
taken 
as prescribed; 
F13.921 
sedative, 
hypnotic, 
or anxiolytic taken 
as prescribed 
(or F13.931 
if 



during 
withdrawal from sedative, 
hypnotic, 
or anxiolytic taken 
as prescribed); 
F15.921 
amphetamine-type 
substance 
or other stimulant 
taken 
as prescribed; 
F16.921 
ketamine 
or other hallucinogen 
taken 
as prescribed 
or for medical 
reasons; 
F19.921 
for medications that 
do 
not 
fit 
into 
any of 
the 
classes (e.g., 
dexamethasone) and 
in 
cases in 
which 
a 
substance 
is judged 
to 
be 
an 
etiological factor but 
the 
specific class of 
substance 
is unknown 
(or F19.931 
if 
during 
withdrawal from medications that 
do 
not 
fit 
into 
any of 
the 
classes, 
taken 
as prescribed). 


F05 
Delirium due 
to 
another medical 
condition: 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings that 
the 
disturbance 
is 
attributable 
to 
the 
physiological consequences of 
another medical condition. 


Coding 
note: 
Include 
the 
name 
of 
the 
other medical condition 
in 
the 
name 
of 
the 
delirium (e.g., 
F05 
delirium due 
to 
hepatic encephalopathy). 
The 
other 
medical condition 
should 
also 
be 
coded 
and 
listed 
separately immediately 
before 
the 
delirium due 
to 
another medical condition 
(e.g., 
K72.90 
hepatic 
encephalopathy; 
F05 
delirium due 
to 
hepatic encephalopathy). 


F05 
Delirium due 
to 
multiple 
etiologies: 
There 
is evidence 
from the 
history, 
physical examination, 
or laboratory findings that 
the 
delirium has more 
than 
one 
etiology (e.g., 
more 
than 
one 
etiological medical condition; 
another medical 
condition 
plus substance 
intoxication 
or medication 
side 
effect). 


Coding 
note: 
Use 
multiple 
separate 
codes reflecting 
specific delirium 
etiologies (e.g., 
K72.90 
hepatic encephalopathy; 
F05 
delirium due 
to 
hepatic 
failure; 
F10.231 
alcohol withdrawal delirium). 
Note 
that 
the 
etiological medical 
condition 
both 
appears as a 
separate 
code 
that 
precedes the 
delirium code 
and 
is substituted 
into 
the 
delirium due 
to 
another medical condition 
rubric. 


Recording Procedures 


Substance 
intoxication 
delirium. 
The name of the substance intoxication delirium 
begins with the 
specific substance (e.g., cocaine) that 
is presumed to be causing the delirium. The diagnostic 
code is selected from 
the table included in the criteria set, which is based on the drug class and 
presence or absence of a comorbid substance use disorder. For substances that 
do not 
fit 
into any 
of the classes (e.g., dexamethasone), the code for  other substance  should be used; 
and in cases 
in which a substance is judged to be an etiological 
factor but 
the specific class of substance is 
unknown, the category  unknown substance  should be used. 


When recording the name of the disorder, the comorbid substance use disorder (if any) is 
listed first, followed by the word  with,  followed by the name of the substance intoxication 
delirium, followed by the course (i.e., acute, persistent), followed by the specifier indicating level 
of psychomotor activity (i.e., hyperactive, hypoactive, mixed level 
of activity). For example, in 
the case of acute hyperactive intoxication delirium 
occurring in a man with a severe cocaine use 
disorder, the diagnosis is F14.221 severe cocaine use disorder with cocaine intoxication delirium, 
acute, hyperactive. A separate diagnosis of the comorbid severe cocaine use disorder is not 
given. If the intoxication delirium 
occurs without 
a comorbid substance use disorder (e.g., after a 
one-time heavy use of the substance), no accompanying substance use disorder is noted (e.g., 



F16.921 phencyclidine intoxication delirium, acute, hypoactive). 


675 


Substance 
withdrawal 
delirium. 
The name of the substance withdrawal 
delirium 
begins with the 
specific substance (e.g., alcohol) that 
is presumed to be causing the withdrawal 
delirium. The 
diagnostic code is selected from 
substance-specific codes in the coding note included in the 
criteria set. When recording the name of the disorder, the comorbid substance use disorder (if 
any) is listed first, followed by the word  with,  followed by the substance withdrawal 
delirium, 
followed by the course (i.e., acute, persistent), followed by the specifier indicating level 
of 
psychomotor activity (i.e., hyperactive, hypoactive, mixed level of activity). For example, in the 
case of acute hyperactive withdrawal 
delirium 
occurring in a man with a severe alcohol 
use 
disorder, the diagnosis is F10.231 severe alcohol 
use disorder with alcohol 
withdrawal 
delirium, 
acute, hyperactive. A separate diagnosis of the comorbid severe alcohol use disorder is not given. 


Medication-induced 
delirium. 
The name of the medication-induced delirium 
begins with the 
specific substance (e.g., dexamethasone) that 
is presumed to be causing the delirium. The name 
of the disorder is followed by the course (i.e., acute, persistent), followed by the specifier 
indicating level 
of psychomotor activity (i.e., hyperactive, hypoactive, mixed level 
of activity). 
For example, in the case of acute hyperactive medication-induced delirium 
occurring in a man 
using dexamethasone as prescribed, the diagnosis is F19.921 dexamethasone-induced delirium, 
acute, hyperactive. 


Specifiers 


Regarding course, in hospital 
settings, delirium 
usually lasts about 
1 week, but 
some symptoms 
often persist even after individuals are discharged from the hospital. 


Individuals with delirium 
may rapidly switch between hyperactive and hypoactive states. The 
hyperactive state may be more common or more frequently recognized and often is associated 
with medication side effects and drug withdrawal. The hypoactive state may be more frequent 
in 
older adults and is often unrecognized among older individuals in emergency departments and 
hospitals. 


Diagnostic Features 


The essential 
feature of delirium 
is an acute impairment 
of consciousness characterized by a 
disturbance in attention accompanied by reduced awareness of the environment, both core 
features of normal 
consciousness. Because these deficits reflect 
an altered state of consciousness 
affecting many higher cerebral 
cortical 
functions of the cerebral 
cortex, they are accompanied by 
a change from 
baseline in other cognitive functions that 
cannot 
be better explained by a 
preexisting or evolving neurocognitive disorder (NCD). The disturbance in attention (Criterion 


A) is manifested by reduced ability to direct, focus, sustain, and shift 
attention. Questions must 
be repeated because the individual s attention wanders, or the individual 
may perseverate with an 
answer to a previous question rather than appropriately shift 
attention. The individual 
is easily 
distracted by irrelevant 
stimuli. The disturbance in awareness affects both internal 
thinking and 
insight as well as difficulty making sense of what is happening in the external environment. 
The disturbance develops over a short 
period of time, usually hours to a few days, and tends 



to fluctuate during the course of the day, often with worsening in the evening and night 
when 
external 
orienting stimuli 
decrease (Criterion B). There is evidence from 
the history, physical 
examination, or laboratory findings that 
the disturbance is a physiological 
consequence of an 
underlying medical 
condition, substance intoxication or withdrawal, use of a medication, or a 
toxin exposure, or a combination of these factors (Criterion E). The etiology should be coded 
according to the etiologically appropriate subtype (i.e., substance or medication intoxication, 
substance withdrawal, another medical 
condition, or multiple etiologies). Delirium 
often occurs 
in the context 
of an underlying NCD. The impaired brain function of individuals with mild and 
major NCD renders them more vulnerable to developing a delirium. 


676 


There is an accompanying change in at 
least 
one other area that 
may include memory and 
learning (particularly recent memory), disorientation (particularly to time and place), alteration in 
language (particularly semantic comprehension), or perceptual 
distortion or a perceptual-motor 
disturbance (Criterion C). The perceptual 
disturbances accompanying delirium 
include 
misinterpretations, illusions, or hallucinations; 
these disturbances are typically visual, but 
may 
occur in other modalities as well, and range from simple and uniform to highly complex. 


Normal 
attention/arousal, delirium, and coma lie on a continuum. Coma 
is defined as a state 
of unconsciousness with an absence of cognition or sleep-wake cycle, along with the lack of any 
meaningful 
response to verbal 
or physical 
stimuli. Delirium 
is an impaired state of consciousness 
in the setting of an aroused cortex. The ability to evaluate cognition to diagnose delirium 
depends on there being a level 
of cortical 
arousal 
and wakefulness sufficient 
for response to 
verbal 
stimulation; 
hence, delirium 
should not 
be diagnosed in the context 
of coma (Criterion D). 
Stuporous individuals also have a reduced level 
of brain arousal, but 
not 
to the extent 
of the 
complete unconsciousness of coma. Coma and stupor can be due to neurological 
conditions or 
drug-induced as with iatrogenic deep sedation in intensive care unit 
(ICU) settings or general 
anesthesia. Those individuals who show only minimal 
responses to verbal 
or physical 
stimulation are incapable of engaging with attempts at 
standardized testing or even interview. 
This inability to engage should be classified as a disorder of arousal 
such as coma or stupor, and 
not 
as delirium. However, delirium 
can be a stage that 
follows emergence from 
coma or stupor, 
especially when coma is the result 
of a neurological 
condition. Further, the sleep-wake cycle 
disturbance characteristic of the circadian rhythm 
disturbance in delirium 
can interfere with full 
assessment 
of the individual 
if in a sleep phase, which should be distinguished from 
a disorder of 
brain arousal. 


Associated Features 


Delirium 
is often associated with a disturbance in the sleep-wake cycle. This disturbance can 
include daytime sleepiness, nighttime agitation, difficulty falling asleep, excessive sleepiness 
throughout 
the day, or wakefulness throughout 
the night. In some cases, complete reversal 
of the 
night-day sleep-wake cycle can occur. Sleep-wake cycle disturbances are very common in 
delirium and have been proposed as a core criterion for the diagnosis. 


The individual 
with delirium 
may exhibit 
emotional 
disturbances, such as anxiety, fear, 
depression, irritability, anger, euphoria, and apathy. There may be rapid and unpredictable shifts 



from 
one emotional 
state to another. The disturbed emotional 
state may also be evident 
in calling 
out, screaming, cursing, muttering, moaning, or making other sounds. These behaviors are 
especially prevalent 
at 
night 
and under conditions in which stimulation and environmental 
cues 
are lacking. 


Prevalence 


The prevalence of delirium 
is highest 
among hospitalized older individuals and varies depending 
on the individuals  characteristics, setting of care, and sensitivity of the detection method. Data 
from 
the United States and Finland indicate that 
the prevalence of delirium 
in the community 
overall 
is low (1% 2%). The prevalence is 8% 17% in older individuals presenting to North 
American emergency departments, where the delirium often indicates a medical illness. 


Based on data from 
various countries, the prevalence of delirium 
when individuals are 
admitted to the hospital 
ranges from 
18% to 35%, and estimates of the occurrence of delirium 
arising during hospitalization range from 
29% to 64% in general 
hospital 
populations. 
Internationally, delirium 
occurs in 11% 51% of older individuals postoperatively and in up to 
81% of those in intensive care. The prevalence of delirium 
ranges from 
20% to 22% in 
individuals in nursing homes or post acute care settings and occurs in up to 88% of individuals 
with terminal 
illness at 
the end of life. Despite having higher risk factors for delirium, such as 
cardiovascular disease, sepsis, and respiratory failure, younger African Americans 


677 


tended to have lower rates of the occurrence of delirium 
compared with White individuals of 
similar age in a large case series of ICU patients in the United States. 


Development and Course 


The majority of individuals with delirium 
have a full 
recovery with or without 
treatment, 
especially those who are not 
elderly. Delirium 
may progress to stupor, coma, seizures, or death, 
particularly if undetected and the underlying cause(s) remains untreated. 


There is increasing evidence that 
delirium 
may be associated in long-term 
follow-up with 
cognitive decline or major NCD in the elderly, particularly in those with preexisting underlying 
cognitive impairment. Mortality among hospitalized individuals with delirium 
is high; 
as many 
as 38% 41% of individuals with delirium 
die within 1 year after diagnosis; 
the risk of death is 
particularly great 
among those with malignancies and other significant 
underlying medical 
illness. 


Risk and Prognostic Factors 


Delirium 
may be increased in the context 
of functional 
impairment, preexisting cognitive 
impairment, sensory impairment 
(e.g., vision/hearing), increasing age, illness severity or 
comorbidity, infection, depression, history of stroke, and history of alcohol 
use. Both major and 
mild NCDs can increase the risk for delirium 
and complicate the course. Falls may be an 
outcome of delirium 
but 
are not 
found to be a risk factor. In a meta-analysis of studies from 
1990 
through 2016, anticholinergic use was not a validated predictor of delirium. 


Older individuals are especially susceptible to delirium 
compared with younger adults. 



Among children, susceptibility to delirium 
in infancy and through childhood may be associated 
with significant 
childhood morbidity and mortality, whereas individuals in early adulthood 
through mid-adulthood may have less susceptibility to delirium and lower mortality risk. 


Sex- and Gender-Related Diagnostic Issues 


The symptoms associated with delirium 
may vary in men and women. Men more commonly 
manifest 
motor agitation and affective lability, whereas women more commonly manifest 
hypoactive delirium. Male sex is a risk factor for delirium, and sex-or gender-related factors 
may interact with other risk factors. 


Diagnostic Markers 


In addition to laboratory findings characteristic of underlying medical 
conditions (or intoxication 
or withdrawal 
states), there is often generalized irregular theta slowing on 
electroencephalography, and fast 
activity is occasionally found (e.g., in some cases of alcohol 
withdrawal 
delirium). However, electroencephalography is unable to detect 
slowing associated 
with delirium 
without 
comparison to premorbid baseline alpha rhythms unless the slowing is in 
the abnormal theta or delta frequency range. 


Functional 
Consequences of Delirium 


Delirium 
itself is associated with increased functional 
decline and risk of institutional 
placement. 
Hospitalized individuals 65 years or older with delirium 
are at 
greater risk for poor outcomes 
following discharge, including mortality, institutionalization, and dementia. 


Differential 
Diagnosis 


Psychotic 
disorders 
and 
bipolar and 
depressive 
disorders 
with 
psychotic 
features. 


Delirium 
that 
is 
characterized by vivid hallucinations, delusions, language disturbances, and agitation must 
be 
distinguished from brief psychotic disorder, schizophrenia, 


678 


schizophreniform 
disorder, and other psychotic disorders, as well 
as from 
manic or major 


depressive episodes, with psychotic features. 
Acute 
stress 
disorder. 
Delirium 
associated with fear, anxiety, and dissociative symptoms, such as 
depersonalization, must 
be distinguished from 
acute stress disorder, which is precipitated by 
exposure to a severely traumatic event. 


Malingering 
and 
factitious 
disorder. 
Delirium 
can be distinguished from 
these disorders on the basis 
of the often atypical 
symptomatic presentation in malingering and factitious disorder and the 
absence of another medical 
condition or substance that 
is etiologically related to the apparent 
cognitive disturbance. 


Other neurocognitive 
disorders. 
The most 
common differential 
diagnostic issue when evaluating 
confusion in older adults is disentangling symptoms of delirium 
and major NCD. The clinician 
must 
determine whether the individual 
has delirium; 
a delirium 
superimposed on a preexisting 
NCD, such as that 
due to Alzheimer s disease; 
or an NCD without 
delirium. The traditional 



distinction between delirium 
and major NCD according to acuteness of onset 
and temporal 
course is particularly difficult 
in those elderly individuals who had a prior NCD that 
may not 
have been recognized, or who developed persistent 
cognitive impairment 
following an episode of 
delirium. When delirium 
and major NCD are comorbid, the management 
of the delirium 
should 
generally be given priority. 


Other Specified 
Delirium 


R41.0 


This category applies to 
presentations in 
which 
symptoms characteristic of 
delirium 
that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other 
important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for 
delirium or any of 
the 
disorders in 
the 
neurocognitive 
disorders diagnostic class. 
The 
other specified 
delirium category is used 
in 
situations in 
which 
the 
clinician 
chooses 
to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for delirium or any specific neurocognitive 
disorder. 
This is done 
by recording 
 other 
specified 
delirium  followed 
by the 
specific reason 
(e.g., 
 subsyndromal delirium ). 


An 
example 
of 
a 
presentation 
that 
can 
be 
specified 
using 
the 
 other specified  
designation 
is the 
following: 


Subsyndromal 
delirium: 
A 
delirium-like 
presentation 
involving 
disturbances in 


attention, 
higher-level thought, 
and 
circadian 
rhythm, 
in 
which 
the 
severity of 


cognitive 
impairment 
falls short 
of 
that 
required 
for the 
diagnosis of 
delirium. 


Unspecified 
Delirium 


R41.0 


This category applies to 
presentations in 
which 
symptoms characteristic of 
delirium 
that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other 
important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for 
delirium or any of 
the 
disorders in 
the 
neurocognitive 
disorders diagnostic class. 
The 
unspecified 
delirium category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for delirium, 
and 
includes 
presentations for which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific 
diagnosis (e.g., 
in 
emergency room settings). 


679 


Major and 
Mild 
Neurocognitive Disorders 



Major Neurocognitive Disorder 


Diagnostic Criteria 


A. 
Evidence 
of 
significant 
cognitive 
decline 
from a 
previous level of 
performance 
in 
one 
or more 
cognitive 
domains (complex attention, 
executive 
function, 
learning 
and 
memory, 
language, 
perceptual-motor, 
or social cognition) based 
on: 
1. 
Concern 
of 
the 
individual, 
a 
knowledgeable 
informant, 
or the 
clinician 
that 
there 
has been 
a 
significant 
decline 
in 
cognitive 
function; 
and 
2. 
A 
substantial impairment 
in 
cognitive 
performance, 
preferably documented 
by 
standardized 
neuropsychological testing 
or, 
in 
its absence, 
another quantified 
clinical assessment. 
B. 
The 
cognitive 
deficits interfere 
with 
independence 
in 
everyday activities (i.e., 
at 
a 
minimum, 
requiring 
assistance 
with 
complex instrumental activities of 
daily living 
such 
as paying 
bills or managing 
medications). 
C. 
The 
cognitive 
deficits do 
not 
occur exclusively in 
the 
context 
of 
a 
delirium. 
D. 
The 
cognitive 
deficits are 
not 
better explained 
by another mental disorder (e.g., 
major depressive 
disorder, 
schizophrenia). 
Specify 
whether due 
to: 
Note: 
Each 
subtype 
listed 
has specific diagnostic criteria 
and 
corresponding 
text, 
which 
follow the 
general discussion 
of 
major and 
mild 
neurocognitive 
disorders. 


Alzheimer s 
disease 
Frontotemporal 
degeneration 
Lewy 
body 
disease 
Vascular disease 
Traumatic 
brain 
injury 
Substance/medication 
use 
HIV 
infection 
Prion 
disease 
Parkinson s 
disease 
Huntington s 
disease 
Another medical 
condition 
Multiple 
etiologies 
Unspecified 
etiology 


Coding 
note: 
Code 
based 
on 
medical or substance 
etiology. 
In 
most 
cases of 
major 
neurocognitive 
disorder, 
there 
is need 
for an 
additional code 
for the 
etiological 
medical condition, 
which 
must 
immediately precede 
the 
diagnostic code 
for major 
neurocognitive 
disorder, 
as noted 
in 
the 
coding 
table 
on 
pp. 
682 683. 



Specify (see 
coding 
table 
for details): 


Without behavioral 
disturbance: 
If 
the 
cognitive 
disturbance 
is not 


accompanied 
by any clinically significant 
behavioral disturbance. 
With 
behavioral 
disturbance 
(specify disturbance): 
If 
the 
cognitive 
disturbance 
is accompanied 
by a 
clinically significant 
behavioral disturbance 
(e.g., 
psychotic 
symptoms, 
mood 
disturbance, 
agitation, 
apathy, 
or other behavioral symptoms). 


680 


Coding 
note: 
Use 
additional code(s) to 
indicate 
clinically significant 
psychiatric 
symptoms due 
to 
the 
same 
medical condition 
causing 
the 
major neurocognitive 
disorder (e.g., 
F06.2 
psychotic disorder due 
to 
Alzheimer s disease, 
with 
delusions; 
F06.32 
depressive 
disorder due 
to 
Parkinson s disease, 
with 
major 
depressive like 
episode). 
Note: 
Mental disorders due 
to 
another medical 
condition 
are 
included 
with 
disorders with 
which 
they share 
phenomenology 
(e.g., 
for depressive 
disorders due 
to 
another medical condition, 
see 
the 
chapter 
 Depressive 
Disorders ). 


Specify 
current 
severity: 
Mild: 
Difficulties with 
instrumental activities of 
daily living 
(e.g., 
housework, 
managing 
money). 
Moderate: 
Difficulties with 
basic activities of 
daily living 
(e.g., 
feeding, 
dressing). 
Severe: 
Fully dependent. 


Coding 
and 
Recording 
Procedures 


The 
following 
are 
examples of 
coding 
and 
recording 
major neurocognitive 
disorders 
due 
to 
an 
etiological subtype 
(for more 
information, 
see 
coding 
table 
on 
pp. 
682 683 
and 
coding 
notes in 
the 
specific diagnostic criteria 
for each 
major and 
mild 
neurocognitive 
disorder subtype): 


Major neurocognitive 
disorder due 
to 
probable 
Alzheimer s 
disease, 
without behavioral 
disturbance, 
mild: 
G30.9 
Alzheimer s disease, 
F02.80 
major neurocognitive 
disorder due 
to 
probable 
Alzheimer s disease, 
without 
behavioral disturbance, 
mild. 


Major neurocognitive 
disorder due 
to 
traumatic 
brain 
injury, 
with 
behavioral 
disturbance, 
moderate: 
S06.2X9S 
diffuse 
traumatic brain 
injury 
with 
loss of 
consciousness of 
unspecified 
duration, 
sequela; 
F02.81 
major 
neurocognitive 
disorder due 
to 
traumatic brain 
injury, 
with 
behavioral 
disturbance, 
moderate; 
F06.34 
bipolar and 
related 
disorder due 
to 
traumatic 
brain 
injury, 
with 
mixed 
features. 


Mild Neurocognitive Disorder 


Diagnostic Criteria 



A. 
Evidence 
of 
modest 
cognitive 
decline 
from a 
previous level of 
performance 
in 
one 
or more 
cognitive 
domains (complex attention, 
executive 
function, 
learning 
and 
memory, 
language, 
perceptual-motor, 
or social cognition) based 
on: 
1. 
Concern 
of 
the 
individual, 
a 
knowledgeable 
informant, 
or the 
clinician 
that 
there 
has been 
a 
mild 
decline 
in 
cognitive 
function; 
and 
2. 
A 
modest 
impairment 
in 
cognitive 
performance, 
preferably documented 
by 
standardized 
neuropsychological testing 
or, 
in 
its absence, 
another quantified 
clinical assessment. 
B. 
The 
cognitive 
deficits do 
not 
interfere 
with 
capacity for independence 
in 
everyday 
activities (i.e., 
complex instrumental activities of 
daily living 
such 
as paying 
bills 
or managing 
medications are 
preserved, 
but 
greater effort, 
compensatory 
strategies, 
or accommodation 
may be 
required). 
C. 
The 
cognitive 
deficits do 
not 
occur exclusively in 
the 
context 
of 
a 
delirium. 
D. 
The 
cognitive 
deficits are 
not 
better explained 
by another mental disorder (e.g., 
major depressive 
disorder, 
schizophrenia). 
681 


Specify 
whether due 
to: 
Note: 
Each 
subtype 
listed 
has specific diagnostic criteria 
and 
corresponding 
text, 
which 
follow the 
general discussion 
of 
major and 
mild 
neurocognitive 
disorders. 


Alzheimer s 
disease 
Frontotemporal 
degeneration 
Lewy 
body 
disease 
Vascular disease 
Traumatic 
brain 
injury 
Substance/medication 
use 
HIV 
infection 
Prion 
disease 
Parkinson s 
disease 
Huntington s 
disease 
Another medical 
condition 
Multiple 
etiologies 
Unspecified 
etiology 


Coding 
note: 
For mild 
neurocognitive 
disorder due 
to 
any of 
the 
medical etiologies 
listed 
above, 
code 
G31.84. 
Do 
not 
use 
additional codes for the 
presumed 
etiological 
medical conditions. 
For substance/medication-induced 
mild 
neurocognitive 
disorder, 
code 
based 
on 
type 
of 
substance; 
see 
 Substance/Medication-Induced 
Major or Mild 
Neurocognitive 
Disorder.  For unspecified 
mild 
neurocognitive 
disorder, 
code 
R41.9. 



Specify (behavioral disturbance 
cannot 
be 
coded 
but 
should 
still be 
recorded): 


Without behavioral 
disturbance: 
If 
the 
cognitive 
disturbance 
is not 


accompanied 
by any clinically significant 
behavioral disturbance. 
With 
behavioral 
disturbance 
(specify disturbance): 
If 
the 
cognitive 
disturbance 
is accompanied 
by a 
clinically significant 
behavioral disturbance 
(e.g., 
psychotic 
symptoms, 
mood 
disturbance, 
agitation, 
apathy, 
or other behavioral symptoms). 
Coding 
note: 
Use 
additional code(s) to 
indicate 
clinically significant 
psychiatric 
symptoms due 
to 
the 
same 
medical condition 
causing 
the 
mild 
neurocognitive 
disorder (e.g., 
F06.2 
psychotic disorder due 
to 
traumatic brain 
injury, 
with 
delusions; 
F06.32 
depressive 
disorder due 
to 
HIV 
disease, 
with 
major 
depressive like 
episode). 
Note: 
Mental disorders due 
to 
another medical 
condition 
are 
included 
with 
disorders with 
which 
they share 
phenomenology 
(e.g., 
for depressive 
disorders due 
to 
another medical condition, 
see 
the 
chapter 
 Depressive 
Disorders ). 


Coding 
and 
Recording 
Procedures 


The 
following 
are 
examples of 
coding 
and 
recording 
mild 
neurocognitive 
disorders 
due 
to 
an 
etiological subtype 
(for more 
information, 
see 
coding 
table 
on 
pp. 
682 683 
and 
coding 
notes in 
the 
specific diagnostic criteria 
for each 
major and 
mild 
neurocognitive 
disorder subtype): 


G31.84 
Mild 
neurocognitive 
disorder due 
to 
Alzheimer s disease, 
without 


behavioral disturbance. 
G31.84 
Mild 
neurocognitive 
disorder due 
to 
traumatic brain 
injury, 
with 
behavioral disturbance; 
F06.34 
bipolar and 
related 
disorder due 
to 
traumatic 
brain 
injury, 
with 
mixed 
features. 


682 


Associated 
etiological 
medical 
code 
for major 
Major 
neurocognitive 
neurocognitive 


Etiological 
subtype 
disordera 
disorder code 
Mild 
neurocognitive 
disorder code 


Alzheimer s disease 
G30.9 
F02.8xb 
G31.84c 
Do 
not 
use 
additional code 
for 
Alzheimer s disease. 


Frontotemporal 
G31.09 
F02.8xb 
G31.84c 
Do 
not 
use 
additional code 
for 
degeneration 
frontotemporal degeneration. 


Lewy body disease 
G31.83 
F02.8xb 
G31.84c 
Do 
not 
use 
additional code 
for 
Lewy body disease. 


Vascular 
disease 
No 
additional 
F01.5xb 
Do 
not 
use 
G31.84c 
Do 
not 
use 
additional code 
for 
the 
medical code. 
additional code 
for 
the 
vascular 
disease. 
vascular 
disease. 


Traumatic brain 
injury 
S06.2X9S 
F02.8xb 
G31.84c 
Do 
not 
use 
additional code 
for 
the 
traumatic brain 
injury. 


Substance/medication-No 
additional 
Code 
based 
on 
the 
Code 
based 
on 
the 
type 
of 
substance 


induced 
medical code. 
type 
of 
substance 
causing 
the 
mild 
neurocognitive 
disorder.d 
causing 
the 
major 



causing 
the 
major 
neurocognitive 
disorder.d 


HIV infection 
B20 
F02.8xb 
G31.84c 
Do 
not 
use 
additional code 
for 
HIV infection. 


Prion 
disease 
A81.9 
F02.8xb 
G31.84c 
Do 
not 
use 
additional code 
for 
prion 
disease. 


Parkinson s disease 
G20 
F02.8xb 
G31.84c 
Do 
not 
use 
additional code 
for 
Parkinson s disease. 


683 
G10 
F02.8xb 
G31.84c 
Do 
not 
use 
additional code 
for 
Huntington s disease. 
Huntington s disease 
Due 
to 
another 
Code 
the 
other 
F02.8xb 
G31.84c 
Do 
not 
use 
additional codes for 
medical condition 
medical condition 
first 
(e.g., 
G35 
multiple 
sclerosis). 
the 
presumed 
etiological medical 
conditions. 


Due 
to 
multiple 
etiologies 
Code 
all of 
the 
etiological medical 
conditions first 
(with 
the 
exception 
of 
vascular 
disease). 
F02.8xb 
(code 
once 
for 
major 
neurocognitive 
disorder 
due 
to 
all 
etiologies that 
apply) 
Code 
also 
major 
vascular 
NCD 
G31.84c 
Do 
not 
use 
additional codes for 
the 
presumed 
etiological medical 
conditions. 
Code 
also 
the 
relevant 
substance/medication-induced 
mild 
neurocognitive 
disorders if 
substances or 
medications play a 
role 
in 
the 
etiology. 
(F01.5x), 
if 
present. 
Code 
also 
the 
relevant 
substance/medicationinduced 
major 
neurocognitive 
disorders if 
substances or 
medications play a 
role 
in 
the 
etiology. 
Unspecified 
neurocognitive 
disorder 
No 
additional 
medical code. 
R41.9c 
R41.9c 


aCode first, before code for major neurocognitive disorder. 
bCode fifth character 
based on symptom 
specifier: 
.x0 without 
behavioral 
disturbance; 
.x1 with behavioral 
disturbance 


(e.g., psychotic symptoms, mood disturbance, agitation, apathy, or 
other 
behavioral 
symptoms). Note: 
The severity 
specifiers  mild,   moderate,  and  severe  cannot be coded for major neurocognitive disorder but should still be recorded. 
cNote:  With behavioral disturbance  and  without behavioral disturbance  cannot be coded but should still be recorded. 
dSee coding table in  Substance/Medication-Induced Major 
or 
Mild Neurocognitive Disorder  for 
ICD-10-CM code. Note: 


The severity specifiers  mild,   moderate,  and  severe  (for 
substance/medication-induced major 
neurocognitive 
disorder) 
and the accompanying symptom 
specifiers  with behavioral 
disturbance  and  without 
behavioral 
disturbance  
(for substance/medication-induced major or mild neurocognitive disorder) cannot be coded but should still be recorded. 


684 


Subtypes 


Major and mild neurocognitive disorders (NCDs) are primarily subtyped according to the known 
or presumed etiological/pathological 
entity or entities underlying the cognitive decline. These 
subtypes are distinguished on the basis of a combination of time course, characteristic domains 
affected, and associated symptoms. For certain etiological 
subtypes, the diagnosis depends 
substantially on the presence of a potentially causative entity, such as Parkinson s or 



Huntington s disease, or a traumatic brain injury or stroke in the appropriate time period. For 
other etiological 
subtypes (generally the neurodegenerative diseases like Alzheimer s disease, 
frontotemporal 
degeneration, and Lewy body disease), the diagnosis is based primarily on the 
cognitive, behavioral, and functional 
symptoms. Typically, the differentiation among these 
syndromes that 
lack an independently recognized etiological 
entity is clearer at 
the level 
of major 
NCD than at 
the level 
of mild NCD, but 
sometimes characteristic symptoms and associated 
features are present at the mild level as well. 


NCDs are frequently managed by clinicians in multiple disciplines. For many subtypes, 
multidisciplinary international 
expert 
groups have developed specialized consensus criteria based 
on clinicopathological 
correlation with underlying brain pathology. The subtype criteria here 
have been harmonized with those expert criteria. 


Specifiers 


Evidence for distinct 
behavioral 
features in NCDs has been recognized, particularly in the areas 
of psychotic symptoms and depression. Psychotic features are common in many NCDs, 
particularly at 
the mild-to-moderate stage of major NCDs due to Alzheimer s disease, Lewy 
body disease, and frontotemporal 
degeneration. If the psychotic symptoms are judged to be due 
to the Alzheimer s disease, Lewy body disease, or frontotemporal 
degeneration, an additional 
diagnosis of psychotic disorder due to Alzheimer s disease, psychotic disorder due to Lewy body 
disease, or psychotic disorder due to frontotemporal 
degeneration may be given. Paranoia and 
other delusions are common features, and often a persecutory theme may be a prominent 
aspect 
of delusional 
ideation. In contrast 
to psychotic disorders with onset 
in earlier life (e.g., 
schizophrenia), disorganized speech and disorganized behavior are not 
characteristic of 
psychosis in NCDs. Hallucinations may occur in any modality, although visual 
hallucinations are 
more common in NCDs than in depressive, bipolar, or psychotic disorders. 


Mood disturbances, including depression, anxiety, and elation, may occur. Depression is 
common early in the course (including at 
the mild NCD level) of NCD due to Alzheimer s 
disease and Parkinson s disease, while elation may occur more commonly in frontotemporal 
degeneration. If the mood disturbance is judged to be due to the Alzheimer s disease, 
Parkinson s disease, or frontotemporal 
degeneration, an additional 
diagnosis of depressive 
disorder due to Alzheimer s disease, depressive disorder due to Parkinson s disease, or bipolar 
and related disorder due to frontotemporal 
degeneration may be given. Mood symptoms are 
increasingly recognized to be a significant 
feature in the earliest 
stages of mild NCDs such that 
clinical recognition and intervention may be important. 


Agitation is common in a wide variety of NCDs, particularly in major NCD of moderate to 
severe severity, and often occurs in the setting of confusion or frustration. It 
may arise as 
combative behaviors, particularly in the context 
of resisting caregiving duties such as bathing 
and dressing. Agitation is characterized as disruptive motor or vocal 
activity and tends to occur 
with advanced stages of cognitive impairment across all of the NCDs. 


Individuals with NCD can present 
with a wide variety of behavioral 
symptoms that 
are the 
focus of treatment. Sleep disturbance is a common symptom 
that 
can create a need for clinical 
attention and may include symptoms of insomnia, hypersomnia, and circadian rhythm 
disturbances. 



685 


Apathy is common in mild and major NCD. It 
is observed particularly in NCD due to 
Alzheimer s disease and may be a prominent 
feature of NCD due to frontotemporal 
degeneration. Apathy is typically characterized by diminished motivation and reduced goal-
directed behavior accompanied by decreased emotional 
responsiveness. Symptoms of apathy 
may manifest 
early in the course of NCDs when a loss of motivation to pursue daily activities or 
hobbies may be observed. 


Other important 
behavioral 
symptoms include wandering, disinhibition, hyperphagia, and 
hoarding. Some of these symptoms are characteristic of specific disorders, as discussed in the 
relevant 
sections. When more than one behavioral 
disturbance is observed, each type should be 
noted in writing with the specifier  with behavioral disturbance.  


Diagnostic Features 


Major and mild NCDs exist 
on a spectrum 
of cognitive and functional 
impairment. Major NCD 
roughly corresponds to the condition labeled in ICD-10 and ICD-11 (as well 
as in DSM-IV) as 
dementia. The core feature of NCDs is acquired cognitive decline in one or more cognitive 
domains (Criterion A) based on both 1) a concern about 
cognition on the part 
of the individual, a 
knowledgeable informant, or the clinician, and 2) performance on an objective assessment 
that 
falls below the expected level 
or that 
has been observed to decline over time. Both a concern and 
objective evidence are required because they are complementary. When there is an exclusive 
focus on objective testing, a disorder may go undiagnosed in high-functioning individuals whose 
currently  normal  performance actually represents a substantial 
decline in abilities, or an illness 
may be incorrectly diagnosed in individuals whose currently  low  performance does not 
represent 
a change from 
their own baseline or is a result 
of extraneous factors like test 
conditions 
or a passing illness. Alternatively, excessive focus on subjective symptoms may fail 
to diagnose 
illness in individuals with poor insight, or whose informants deny or fail 
to notice their 
symptoms, or it may be overly sensitive in the so-called worried well. 


A cognitive concern differs from 
a complaint 
in that 
it 
may or may not 
be voiced 
spontaneously. Rather, it 
may need to be elicited by careful 
questioning about 
specific symptoms 
that 
commonly occur in individuals with cognitive deficits (see Table 1 
in the introduction to this 
chapter). For example, memory concerns include difficulty remembering a short 
grocery list 
or 
keeping track of the plot 
of a television program; 
executive concerns include difficulty resuming 
a task when interrupted, organizing tax records, or planning a holiday meal. At 
the mild NCD 
level, the individual 
is likely to describe these tasks as being more difficult 
or as requiring extra 
time or effort 
or compensatory strategies. At 
the major NCD level, such tasks may only be 
completed with assistance or may be abandoned altogether. At 
the mild NCD level, individuals 
and their families may not 
notice such symptoms or may view them 
as normal, particularly in the 
elderly; 
thus, careful 
history taking is of paramount 
importance. The difficulties must 
represent 
changes rather than lifelong patterns: 
the individual 
or informant 
may clarify this issue, or the 
clinician can infer change from 
prior experience with the individual 
or from 
occupational 
or 
other clues. It 
is also critical 
to determine that 
the difficulties are related to cognitive loss rather 
than to motor or sensory limitations. 


Neuropsychological 
testing, with performance compared with norms appropriate to the 



individual s age, sex, educational 
attainment, and cultural 
background, is part 
of the standard 
evaluation of NCDs and is particularly critical 
in the evaluation of mild NCD. The use of 
culturally validated assessment 
instruments is preferred, which are available for many 
racial/ethnic and linguistic populations. For major NCD, performance is typically 2 or more 
standard deviations below appropriate norms (3rd percentile or below). For mild NCD, 
performance typically lies in the 1 2 standard deviation range (between the 3rd and 16th 
percentiles). However, neuropsychological 
testing is not 
available in all 
settings, and 
neuropsychological thresholds are sensitive to the specific test(s) and norms employed, as well as 
to test conditions, sensory limitations, and intercurrent illness. A variety of brief 


686 


office-based or  bedside  assessments, as described in Table 1, can also supply objective 
data in settings where such testing is unavailable or infeasible. In any case, as with cognitive 
concerns, objective performance must 
be interpreted in light 
of the individual s prior 
performance. Optimally, this information would be available from 
a prior administration of the 
same test, but 
often it 
must 
be inferred based on appropriate norms, along with the individual s 
educational 
history, occupation, and other factors. Norms are more challenging to interpret 
in 
individuals with very high or very low levels of education and in individuals being tested outside 
their own language or cultural background. 


Criterion B 
relates to the individual s level 
of independence in everyday functioning. 
Individuals with major NCD will 
have impairment 
of sufficient 
severity so as to interfere with 
independence, such that 
others will 
have to take over tasks that 
the individuals were previously 
able to complete on their own. Individuals with mild NCD will 
have preserved independence, 
although there may be subtle interference with function or a report 
that 
tasks require more effort 
or take more time than previously. 


The distinction between major and mild NCD is inherently arbitrary, and the disorders exist 
along a continuum. Precise thresholds are therefore difficult 
to determine. Careful 
history taking, 
observation, and integration with other findings are required, and the implications of making a 
diagnosis should be considered when an individual s clinical manifestations lie at a boundary. 


Associated Features 


Typically the associated features that 
support 
a diagnosis of major or mild NCD will 
be specific 
to the etiological 
subtype (e.g., neuroleptic sensitivity and visual 
hallucinations in NCD due to 
Lewy body disease). Diagnostic features specific to each of the subtypes are found in the 
relevant sections. 


Prevalence 


The prevalence of NCD varies widely by age and by etiological 
subtype. Overall 
prevalence 
estimates are generally only available for older populations. Among individuals older than 60 
years, prevalence increases steeply with age, so prevalence estimates are more accurate for 
narrow age bands than for broad categories such as  over 65  (where the mean age can vary 
greatly with the life expectancy of the given population). For those etiological 
subtypes 
occurring across the life span, prevalence estimates for NCD are likely to be available, if at 
all, 



only as the fraction of individuals who develop NCD among those with the relevant 
condition 
(e.g., traumatic brain injury, HIV infection). 


Female gender is associated with higher prevalence of dementia overall, and especially 
Alzheimer s disease, but 
this difference is largely, if not 
wholly, attributable to greater longevity 
in females. 


Overall, international 
prevalence estimates for dementia (which is largely congruent 
with 
major NCD) are approximately 1% 2% at 
age 65 years and as high as 30% by age 85 years. The 
prevalence of mild NCD is very sensitive to the definition of the disorder, particularly in 
community settings, where evaluations are less detailed. In addition, in contrast 
with clinical 
settings, where cognitive concern must 
be high to seek and locate care, there may be a less clear 
decline from 
baseline functioning. Estimates of the prevalence of mild cognitive impairment 
(which is substantially congruent 
with mild NCD) among older individuals are fairly variable, 
ranging from 2% to 10% at age 65 and 5% to 25% by age 85. 


Prevalence and incidence of dementia vary cross-nationally and among ethnic and racialized 
populations in the United States, although methodological 
differences complicate rate 
comparisons. Some U.S. studies found that 
incidence is highest 
in African Americans followed, 
in decreasing order, by American Indians/Alaska Natives, Latinx, Pacific Islanders, non-Latinx 
Whites, and Asian Americans. Among four Asian American populations, Filipino Americans had 
the highest incidence, followed by Japanese Americans, Chinese 


687 


Americans, and Asian-Indian Americans. Latinx subpopulations in the United States have 
been found to vary considerably in prevalence and incidence of dementia; 
Caribbean Hispanics 
have much higher rates than Mexican Americans in some U.S. studies. 


Development and Course 


The course of NCD varies across etiological 
subtypes, and this variation can be useful 
in 
differential 
diagnosis. Some subtypes (e.g., those related to traumatic brain injury or stroke) 
typically begin at 
a specific time and (at 
least 
after initial 
symptoms related to inflammation or 
swelling subside) remain static. Others may fluctuate over time (although if this occurs, the 
possibility of delirium 
superimposed on NCD should be considered). NCDs due to 
neurodegenerative diseases like Alzheimer s disease or frontotemporal 
degeneration typically are 
marked by insidious onset 
and gradual 
progression, and the pattern of onset 
of cognitive deficits 
and associated features helps to distinguish among them. 


NCDs with onset 
in childhood and adolescence may have broad repercussions for social 
and 
intellectual 
development, and in this setting intellectual 
developmental 
disorder (intellectual 
disability) or other neurodevelopmental 
disorders may also be diagnosed to capture the full 
diagnostic picture and ensure the provision of a broad range of services. In older individuals, 
NCDs often occur in the setting of medical 
illnesses, frailty, and sensory loss, which complicate 
the clinical picture for diagnosis and treatment. 


When cognitive loss occurs in youth to midlife, individuals and families are likely to seek 
care. NCDs are typically easiest 
to identify at 
younger ages, although in some settings 
malingering or factitious disorder may be a concern. Very late in life, cognitive symptoms may 



not 
cause concern or may go unnoticed. In late life, mild NCD must 
also be distinguished from 
the more modest 
deficits associated with  normal 
aging,  although a substantial 
fraction of what 
has been ascribed to normal 
aging likely represents prodromal 
phases of various NCDs. In 
addition, it 
becomes harder to recognize mild NCD with age because of the increasing 
prevalence of medical 
illness and sensory deficits. It 
becomes harder to differentiate among 
subtypes with age because there are multiple potential sources of neurocognitive decline. 


Risk and Prognostic Factors 


Risk factors vary not 
only by etiological 
subtype but 
also by age at 
onset 
within etiological 
subtypes. Some subtypes are distributed throughout 
the life span, whereas others occur 
exclusively or primarily in late life. Even within the NCDs of aging, the relative prevalence 
varies with age: 
Alzheimer s disease is uncommon before age 60 years, and the prevalence 
increases steeply thereafter, while the overall 
less common frontotemporal 
degeneration has 
earlier onset 
and represents a progressively smaller fraction of NCDs with age. The strongest 
risk 
factor for major and mild NCDs is age, primarily because age increases the risk of 
neurodegenerative and cerebrovascular disease. 


Risk of NCDs varies by ethnic and racialized background and is associated with variation in 
risk of underlying diseases (e.g., hypertension, diabetes), predisposing conditions (e.g., head 
injury), environment 
(e.g., access to nutritious food, safe spaces for exercise), and other factors. 
For example, in the United States, African Americans and Latinx tend to be at 
higher risk for 
vascular dementia than Whites. Lower education and literacy are risk factors for NCDs that 
also 
can vary by ethnoracial 
group because of differential 
exposure to adverse social 
determinants of 
health. 


Culture-Related Diagnostic Issues 


Individuals  and families  level 
of awareness and concern about 
neurocognitive symptoms may 
vary across ethnic, racialized, and occupational 
groups. Cultural 
differences regarding whether 
decreased cognitive ability is seen as a normal 
part 
of aging ( normalization ) and in dementia-
related stigma can delay families  recognition of a problem and 


688 


decrease help seeking for individuals in the early stages of cognitive loss. For example, social 
stigma appears to be associated with underutilization of services for cognitive impairment 
among 
some underserved ethnic and racialized groups (e.g., Chinese Americans, Korean Americans). 


Neurocognitive symptoms are more likely to be noticed, particularly at 
the mild level, in 
individuals who engage in complex occupational, domestic, or recreational 
activities. In addition, 
norms for neuropsychological 
testing tend to be available only for broad populations, and thus 
they may not 
be easily applicable to individuals with less than high school 
education or those 
being evaluated outside their primary language or culture. Culturally related diagnostic 
challenges include accounting for intraethnic variation in the interpretation of assessments; 
evaluating the effect 
on neuropsychological 
testing of a) the test 
taker s stereotype threat 
(i.e., 
anxiety from 
concerns that 
he or she will 
confirm 
the negative stereotype of the ethnic or 
racialized group by underperforming) and/or b) the clinician s implicit 
(unconscious) bias on test 



interpretation; and selecting the appropriate language when assessing bilingual individuals. 


Bilingual 
individuals with dementia may lose their facility with acquired nonnative 
languages, which might 
affect 
their ability to communicate with caregivers. The caregiving 
environment 
may be influenced by cultural 
norms of family responsibility to care for the elderly, 
for example, by affecting the decision whether to care for the elder with NCD at 
home or in a 
care facility. In some cultures, adult 
children are expected to provide care for their older parents 
(e.g., filial 
piety) so that 
a functional 
limitation may not 
be as obvious to the dependent 
elder or 
the family. 


Sex- and Gender-Related Diagnostic Issues 


Some studies show that 
men and women experience major and mild NCD differently. Sex- and 
gender-related factors may influence incidence and prevalence, the etiology (risk and protective 
factors), and the clinical 
manifestations of major and mild NCD. More women than men 
experience major NCD because of their longer life span. Thus, a woman of a given age has a 
higher cumulative risk of developing major NCD before death than a man of the same age. The 
difference in incidence rates is less clear and may vary across populations and over time because 
of gender-related factors (e.g., education, occupation, family role, stress). For example, the 
incidence of dementia in several 
higher-income countries has declined in the past 
30 years, and 
the decline was different 
in men and women across countries. Women tend to express a broader 
range of symptoms. In particular, women tend to manifest 
more psychiatric symptoms such as 
depression, anxiety, and delusions. Men tend to manifest 
more aggression, apathy, and 
vegetative symptoms. 


Like age, culture, and occupation, sex and gender issues may affect 
the level 
of concern and 
awareness of cognitive symptoms. In addition, for late-life NCDs, women are likely to be older, 
to have more medical 
comorbidity, and to live alone, which can complicate evaluation and 
treatment. In addition, there are sex and gender differences in the frequency of some of the 
etiological subtypes. 


Diagnostic Markers 


In addition to a careful 
history, neuropsychological 
assessments are the key measures for 
diagnosis of NCDs, particularly at 
the mild level, where functional 
changes are minimal 
and 
symptoms more subtle. Ideally, individuals will 
be referred for formal 
neuropsychological 
testing, which will 
provide a quantitative assessment 
of all 
relevant 
domains and thus help with 
diagnosis; 
provide guidance to the family on areas where the individual 
may require more 
support; 
and serve as a benchmark for further decline or response to therapies. When such testing 
is unavailable or not 
feasible, the brief assessments in Table 1 
can provide insight 
into each 
domain. More global brief mental status tests may be helpful but may be 


689 


insensitive, particularly to modest 
changes in a single domain or in those with high premorbid 
abilities, and may be overly sensitive in those with low premorbid abilities. 


In distinguishing among etiological 
subtypes, additional 
diagnostic markers may come into 
play, particularly neuroimaging studies such as magnetic resonance imaging scans and positron 



emission tomography scans. In addition, specific markers may be involved in the assessment 
of 
specific subtypes and may become more important 
as additional 
research findings accumulate 
over time, as discussed in the relevant sections. 


Association With Suicidal 
Thoughts or Behavior 


Large-scale studies indicate elevated rates of suicidal 
behavior in individuals with NCD due to a 
variety of etiologies compared with persons without 
an NCD. A nationwide study in Taiwan 
reported that attempted suicide in late life is associated with subsequent dementia. 


Functional 
Consequences of Major and Mild Neurocognitive Disorders 


By definition, major and mild NCDs affect 
functioning, given the central 
role of cognition in 
human life. Thus, the criteria for the disorders, and the threshold for differentiating mild from 
major NCD, are based in part 
on functional 
assessment. Within major NCD there is a broad 
range of functional 
impairment, as implemented in the severity specifiers. In addition, the 
specific functions that 
are compromised can help identify the cognitive domains affected, 
particularly when neuropsychological testing is not available or is difficult to interpret. 


Differential 
Diagnosis 


Normal 
cognition. 
The differential 
diagnosis between normal 
cognition and mild NCD, as 
between mild and major NCD, is challenging because the boundaries are inherently arbitrary. 
Careful 
history taking and objective assessment 
are critical 
to these distinctions. A longitudinal 
evaluation using quantified assessments may be key in detecting mild NCD. 


Delirium. 
Both mild and major NCD may be difficult 
to distinguish from 
a persistent 
delirium, 
which can co-occur. Careful 
assessment 
of attention and arousal 
will 
help to make the 
distinction. 


Major depressive 
disorder. 
The distinction between mild NCD and major depressive disorder, 
which may co-occur with NCD, can also be challenging. Specific patterns of cognitive deficits 
may be helpful. For example, consistent 
memory and executive function deficits are typical 
of 
Alzheimer s disease, whereas nonspecific or more variable performance is seen in major 
depression. Alternatively, treatment 
of the depressive disorder with repeated observation over 
time may be required to make the diagnosis. 


Specific 
learning 
disorder and 
other neurodevelopmental 
disorders. 


A careful 
clarification of the 
individual s baseline status will 
help distinguish an NCD from 
a specific learning disorder or 
other neurodevelopmental 
disorders. Additional 
issues may enter the differential 
for specific 
etiological subtypes, as described in the relevant sections. 


Comorbidity 


NCDs are common in older individuals and thus often co-occur with a wide variety of age-
related diseases that 
may complicate diagnosis or treatment. Most 
notable of these is delirium, 
for which NCD increases the risk. In older individuals, a delirium 
during hospitalization is, in 
many cases, the first 
time that 
an NCD is noticed, although a careful 
history will 
often reveal 
evidence of earlier decline. Mixed NCDs are also common in older 



690 


individuals, as many etiological 
entities increase in prevalence with age. In younger individuals, 
NCD often co-occurs with neurodevelopmental 
disorders; 
for example, a head injury in a 
preschool 
child may also lead to significant 
developmental 
and learning issues. Additional 
comorbidity of NCD is often related to the etiological 
subtype, as discussed in the relevant 
sections. 


Major or Mild 
Neurocognitive Disorder Due to 
Alzheimer s 
Disease 


Diagnostic Criteria 


A. 
The 
criteria 
are 
met 
for major or mild 
neurocognitive 
disorder. 
B. 
There 
is insidious onset 
and 
gradual progression 
of 
impairment 
in 
one 
or more 
cognitive 
domains (for major neurocognitive 
disorder, 
at 
least 
two 
domains must 
be 
impaired). 
C. 
Criteria 
are 
met 
for either probable 
or possible 
Alzheimer s disease 
as follows: 
For major neurocognitive 
disorder: 


Probable 
Alzheimer s 
disease 
is diagnosed 
if 
either of 
the 
following 
is present; 
otherwise, 
possible 
Alzheimer s 
disease 
should 
be 
diagnosed. 


1. 
Evidence 
of 
a 
causative 
Alzheimer s disease 
genetic mutation 
from family 
history or genetic testing. 
2. 
All three 
of 
the 
following 
are 
present: 
a. 
Clear evidence 
of 
decline 
in 
memory and 
learning 
and 
at least 
one 
other 
cognitive 
domain 
(based 
on 
detailed 
history or serial neuropsychological 
testing). 
b. 
Steadily progressive, 
gradual decline 
in 
cognition, 
without 
extended 
plateaus. 
c. 
No 
evidence 
of 
mixed 
etiology (i.e., 
absence 
of 
other neurodegenerative 
or cerebrovascular disease, 
or another neurological, 
mental, 
or systemic 
disease 
or condition 
likely contributing 
to 
cognitive 
decline). 
For mild 
neurocognitive 
disorder: 


Probable 
Alzheimer s 
disease 
is diagnosed 
if 
there 
is evidence 
of 
a 
causative 


Alzheimer s disease 
genetic mutation 
from either genetic testing 
or family history. 
Possible 
Alzheimer s 
disease 
is diagnosed 
if 
there 
is no 
evidence 
of 
a 
causative 
Alzheimer s disease 
genetic mutation 
from either genetic testing 
or 
family history, 
and 
all three 
of 
the 
following 
are 
present: 


1. 
Clear evidence 
of 
decline 
in 
memory and 
learning. 
2. 
Steadily progressive, 
gradual decline 
in 
cognition, 
without 
extended 
plateaus. 

3. 
No 
evidence 
of 
mixed 
etiology (i.e., 
absence 
of 
other neurodegenerative 
or 
cerebrovascular disease, 
or another neurological or systemic disease 
or 
condition 
likely contributing 
to 
cognitive 
decline). 
D. 
The 
disturbance 
is not 
better explained 
by cerebrovascular disease, 
another 
neurodegenerative 
disease, 
the 
effects of 
a 
substance, 
or another mental, 
neurological, 
or systemic disorder. 
Coding 
note 
(see 
coding 
table 
on 
pp. 
682 683): 


For major neurocognitive 
disorder due 
to 
probable 
or possible 
Alzheimer s disease, 
with 
behavioral disturbance, 
code 
first 
G30.9 
Alzheimer s disease, 
followed 
by 
F02.81. 
For major neurocognitive 
disorder due 
to 
probable 
or possible 
Alzheimer s 
disease, 
without 
behavioral disturbance, 
code 
first 
G30.9 
Alzheimer s disease, 
followed 
by F02.80. 


691 


Note: 
The 
severity specifiers  mild,   moderate,  and 
 severe  cannot 
be 
coded 
for 


major neurocognitive 
disorder but 
should 
still be 
recorded. 
For mild 
neurocognitive 
disorder due 
to 
Alzheimer s disease, 
code 
G31.84. 
(Note: 
Do 
not 
use 
the 
additional code 
for Alzheimer s disease. 
 With 
behavioral 
disturbance  and 
 without 
behavioral disturbance  cannot 
be 
coded 
but 
should 
still 
be 
recorded.) 


For major or mild 
neurocognitive 
disorder due 
to 
Alzheimer s disease: 
Use 
additional 
code(s) to 
indicate 
clinically significant 
psychiatric symptoms due 
to 
Alzheimer s 
disease 
(e.g., 
F06.2 
psychotic disorder due 
to 
Alzheimer s disease, 
with 
delusions; 
F06.32 
depressive 
disorder due 
to 
Alzheimer s disease, 
with 
major depressive like 
episode). 


Diagnostic Features 


Beyond the neurocognitive disorder (NCD) syndrome (Criterion A), the core features of major or 
mild NCD due to Alzheimer s disease include an insidious onset 
and gradual 
progression of 
cognitive and behavioral 
symptoms (Criterion B). The typical 
presentation is amnestic (i.e., with 
impairment 
in memory and learning). Unusual 
nonamnestic presentations, particularly 
visuospatial 
and logopenic aphasic variants, also exist. A significant 
proportion of individuals, 
likely more than half, first 
present 
with behavioral 
symptoms before the onset 
of cognitive 
symptoms; the presence of behavioral disturbance should be noted using the appropriate specifier 
codes. At 
the mild NCD phase, Alzheimer s disease manifests typically with impairment 
in 
memory and learning, sometimes accompanied by deficits in executive function. At 
the major 
NCD phase, visuoconstructional/perceptual-motor ability and language (e.g., word retrieval) will 
also be impaired, particularly when the NCD is moderate to severe. Social 
cognition tends to be 
preserved until 
late in the course of the disease with the exception of individuals who have the 
less common variants with significant dysexecutive and behavioral disturbance. 


A level 
of diagnostic certainty must 
be specified denoting Alzheimer s disease as the 
 probable  or  possible  etiology (Criterion C). Probable Alzheimer s disease 
is diagnosed in 



both major and mild NCD if there is evidence of a causative Alzheimer s disease gene, either 
from 
genetic testing or from 
an autosomal 
dominant 
family history coupled with autopsy 
confirmation or a genetic test 
in an affected family member. At 
present, the designation of 
 probable  represents the highest 
level 
of diagnostic certainty within the current 
criteria 
framework. However, current 
developments in biomarkers continue to increase diagnostic 
certainty (e.g., when brain positron emission tomography [PET] scans may indicate the presence 
of Alzheimer s pathology, such as evidence of amyloid and/or tau deposition by imaging or 
cerebrospinal 
[CSF] analysis). For major NCD, a typical 
clinical 
picture, without 
extended 
plateaus or evidence of mixed etiology, can also be diagnosed as due to probable Alzheimer s 
disease. However, in some individuals there may be prolonged periods of very slow or minimal 
progression. For mild NCD, given the lesser degree of certainty that 
the deficits will 
progress, 
these features are only sufficient 
for a possible 
Alzheimer s etiology. As stated above, however, 
new biomarker methods may affect 
the use of  probable  and  possible  in mild NCD. If the 
etiology appears mixed, mild NCD due to multiple etiologies should be diagnosed. In any case, 
for both mild and major NCD due to Alzheimer s disease, the clinical 
features must 
not 
suggest 
another primary etiology for the NCD (Criterion D). As biomarker data continue to inform 
the 
nature of underlying pathologies, it 
is likely that 
the existence of multiple etiologies will 
be more 
systematically mapped in the future to better identify diagnostic variations in NCD due to 
multiple etiologies. 


Associated Features 


For individuals with NCD due to Alzheimer's disease, symptoms extend beyond cognitive 
deficits to include neuropsychiatric symptoms such as agitation, apathy, depression, delusions, 
and sleep disorders. Neuropsychiatric symptoms may also be described as 


692 


behavioral 
and psychological 
symptoms of dementia and have been observed in neurocognitive 
disorders of all 
etiologies. These symptoms are nearly universal 
in Alzheimer's disease as 
confirmed in two U.S. population samples, with 5-year follow-up in one reporting that 
98% of 
individuals with NCD due to Alzheimer's disease develop neuropsychiatric symptoms. 
Neuropsychiatric symptoms lead to disability, worsening quality of life, greater impairment 
in 
activities of daily living, faster cognitive and functional 
decline, greater caregiver burden, earlier 
institutionalization, and accelerated mortality. Neuropsychiatric symptoms are often more 
distressing than cognitive manifestations and are frequently the reason that 
health care assistance 
is sought. These symptoms are also frequently present 
at 
the mild NCD stage, with evidence 
suggesting that 
more than half of individuals who develop dementia begin with neuropsychiatric 
symptoms. At 
the mild NCD stage or the mildest 
level 
of major NCD, depression, irritability, 
and/or apathy are most 
often seen. With moderately severe major NCD, delusions, agitation, 
combativeness, and wandering are common. Late in the illness, gait 
disturbance, dysphagia, 
incontinence, myoclonus, and seizures are observed. 


Prevalence 


The prevalence of overall 
NCD due to Alzheimer s disease rises steeply with age. In high



income countries, it 
ranges from 
5% to 10% in individuals ages 60 69 years to at 
least 
25% 
thereafter. An estimated 5.4 million Americans of all 
ages had dementia due to Alzheimer s 
disease in 2016, including about 
200,000 individuals with disease onset 
before age 65. Dementia 
due to Alzheimer s disease is found in 11% of individuals age 65 and older and 32% of those age 
85 and older. Estimates applying incidence rates of dementia due to Alzheimer s disease to U.S. 
census data indicate that 
81% of those with the disease are age 75 or older. The percentage of 
dementias attributable to Alzheimer s disease ranges from 
about 
60% to over 90%, depending on 
the setting and diagnostic criteria. Mild NCD due to Alzheimer s disease is likely to represent 
a 
substantial fraction of mild cognitive impairment (MCI) as well. 


Studies show that 
prevalence of dementia due to Alzheimer s disease tends to vary by 
ethnoracial 
background; 
for example, in the United States, prevalence in individuals age 65 years 
and older ranges from 
3.5% to 14.4%, depending on ethnoracial 
group, age, and assessment 
methodology. Higher prevalence has been found among African Americans and U.S. Latinx of 
Caribbean origin, after adjustment for gender and clinical comorbidities. 


Development and Course 


Major or mild NCD due to Alzheimer s disease progresses gradually, at 
times with plateaus, 
through severe dementia to death. The mean duration of survival 
after diagnosis is approximately 
10 years, reflecting the advanced age of the majority of individuals rather than the course of the 
disease; 
some individuals can live with the disease for as long as 20 years. Late-stage individuals 
are eventually mute and bedbound. Death most 
commonly results from 
aspiration in those who 
survive through the full 
course. In mild NCD due to Alzheimer s disease, impairments increase 
over time, and functional 
status gradually declines until 
symptoms reach the threshold for the 
diagnosis of major NCD. 


The onset 
of symptoms is usually at 
ages 70 through 89; 
early-onset 
forms seen in 
individuals ages 40 59 are often, but 
not 
always, related to known causative mutations. 
Symptoms and pathology do not 
differ much by onset 
ages. However, younger individuals are 
more likely to survive the full 
course of the disease, while older individuals are more likely to 
have numerous medical 
comorbidities that 
affect 
the course and management 
of the illness. 
Diagnostic complexity is higher in older adults because of the increased likelihood of comorbid 
medical 
illness and mixed pathology. Age at 
symptom 
onset, rate of cognitive decline, and 
survival rates appear to vary by ethnoracial background. For example, compared 


693 


with non-Latinx Whites, U.S. Latinx can develop Alzheimer s disease symptoms up to 4 
years earlier, African Americans tend to show slower cognitive decline, and both underserved 
groups may have longer survival periods. 


Risk and Prognostic Factors 


A number of risk factors have been identified, including low educational 
status, midlife 
hypertension, obesity, and hearing loss, as well 
as late-life smoking, depression, physical 
inactivity, social 
isolation, and diabetes. The co-occurrence of multiple vascular risk factors also 
increases risk for Alzheimer s disease and may act 
by increasing cerebrovascular pathology or 



also through direct 
effects on Alzheimer s pathology. Traumatic brain injury, especially in men, 
may increase risk for major or mild NCD due to Alzheimer s disease, although this relationship 
remains controversial. 


Genetic 
and 
physiological. 
Age is definitively the strongest 
risk factor for Alzheimer s disease, as 
the prevalence estimates demonstrate. A strong genetic predisposition (60% 80% of attributable 
risk) has been demonstrated. Rare mutations on chromosomes 1, 14, and 21 follow Mendelian 
inheritance, leading to autosomal 
dominant 
forms. Individuals with Down syndrome (trisomy 


21) may develop Alzheimer s disease if they survive to midlife. The most 
common risk factors 
are polygenic, with more than 45 risk genes/loci 
having been identified, typically with small 
effects on risk. The strongest 
genetic susceptibility polymorphism, apolipoprotein E4 
(APOE*E4), increases risk and decreases age at 
onset, particularly in homozygous individuals, 
although some homozygous individuals survive to advanced ages without developing symptoms. 
Ethnoracial 
and national 
origin are related to the genetic susceptibility profile for 
Alzheimer s disease. While APOE*E4 
is associated with Alzheimer s disease risk, this 
association has not 
been consistently found across all 
ethnic and racialized groups. For example, 
some studies have identified a unique mutation in the Gly206Ala 
presenilin 1 gene among 
individuals of Puerto Rican descent 
with Alzheimer s disease, which is also related to early 
onset. Moreover, some studies have found a stronger association with ABCA7, a protein 
transporter gene, among individuals who identify as African American than among U.S. Whites. 


Culture-Related Diagnostic Issues 


Detection of an NCD may be more difficult 
in cultural 
and socioeconomic settings where 
memory loss is considered normal 
in old age, where older adults face fewer cognitive demands 
in everyday life, or where very low educational 
levels pose greater challenges to objective 
cognitive assessment. 


Sex- and Gender-Related Diagnostic Issues 


Women were found to have a higher incidence of Alzheimer s disease than men in several 
European studies, but 
the incidence was similar in men and women in most 
North American 
studies. Some studies suggested that 
the symptoms of dementia progress faster in women than in 
men. However, because women perform 
better than men of the same age on some verbal 
memory tests, it 
is also possible that 
gender differences reflect 
the cut-off scores of tests used to 
support 
a diagnosis. Different 
cut-off scores may be useful 
in men and women when assessing 
for mild cognitive impairment. 


Diagnostic Markers 


Amyloid-predominant 
neuritic plaques, tau-predominant 
neurofibrillary tangles, and neuronal 
loss observed microscopically or manifested in regional 
cortical 
atrophy (e.g., hippocampal, 
parietal, frontal) are hallmarks of the pathological 
diagnosis of Alzheimer s disease and may be 
confirmed via postmortem histopathological examination. For 


694 


early-onset 
cases with apparent 
autosomal 
dominant 
inheritance, a mutation in one of the known 



causative Alzheimer s disease genes amyloid precursor protein (APP), presenilin 1 (PSEN1), 
or presenilin 2 (PSEN2) may be involved, and genetic testing for such mutations is 
commercially available, although usually without 
clinical 
utility. While APOE 
E*4 
cannot 
serve 
as a diagnostic marker because it 
is a risk factor (i.e., neither necessary nor sufficient 
for disease 
occurrence), in rare instances genetic testing at this locus may have utility in clinical settings. 


Since amyloid beta-42 deposition in the brain occurs early in the pathophysiological 
cascade, 
amyloid-based diagnostic tests such as amyloid imaging on brain PET 
scans and reduced levels 
of amyloid beta-42 in the CSF 
may have diagnostic value. Similarly, tau PET 
imaging or CSF 
analyses for elevated total 
tau or phospho-tau levels are available for clinical 
use. Signs of 
neuronal 
injury, such as hippocampal 
and temporoparietal 
cortical 
atrophy on a magnetic 
resonance image scan and temporoparietal 
hypometabolism 
on a fluorodeoxyglucose PET 
scan, 
provide evidence of neuronal 
damage but 
are less specific for Alzheimer s disease. Most 
of these 
biomarkers have been validated and are widely available in tertiary care settings. Blood-derived 
biomarkers for Alzheimer s disease are being developed and are likely to become clinically 
available as diagnostic, prognostic, and theranostic indicators. 


Association With Suicidal 
Thoughts or Behavior 


Alzheimer s disease is associated with a moderate risk of suicide even many years after the 
diagnosis; 
thus, ongoing assessment 
of mood and suicidality is appropriate. A large population 
study in Denmark found that 
the risk of suicide in individuals with a hospital-determined 
diagnosis of dementia was three- to eightfold greater compared with persons without 
dementia. 
In contrast, several 
other studies found mixed results regarding suicide risk in individuals with 
Alzheimer s disease. A review of the neurobiology of suicide in the elderly found preliminary 
evidence of an association with cognitive deficits and elderly suicidal 
behavior, especially 
regarding impaired decision-making and reduced cognitive inhibition. 


Functional 
Consequences of Major or Mild Neurocognitive Disorder 
Due to Alzheimer s Disease 


Because of the effect 
on cognition, behavior, and functioning, NCD due to Alzheimer s disease 
has a serious and substantial 
impact 
on individuals, their caregivers, and families. Early in the 
disease course, memory loss, disorientation, and mood 
symptoms adversely impact 
independence, and create safety concerns (e.g., around driving). For individuals with onset 
at 
younger ages, NCD due to Alzheimer s disease can lead to early retirement. As the disease 
advances, individuals become increasingly disabled in instrumental 
and basic daily living 
activities, slowly becoming fully dependent 
on others. Caregivers for individuals with NCD due 
to Alzheimer s disease often see their social 
network deteriorate and develop a series of health 
and mental 
health problems that 
can adversely affect 
outcomes for both the caregiver and the 
individual with the NCD. 


Differential 
Diagnosis 


Other neurocognitive 
disorders. 
Major and mild NCDs due to other neurodegenerative processes 
(e.g., Lewy body disease, frontotemporal 
degeneration) share the insidious onset 
and gradual 
decline caused by Alzheimer s disease but 
have distinctive core features of their own (which are 



not 
always present). For example, NCD with Lewy bodies is typically characterized by frequent 
fluctuations in cognition early in the disease, parkinsonian features, gait 
imbalances, and visual 
hallucinations. Individuals with frontotemporal 
NCD may present 
with a distinct 
behavioral 
or 
language variant. The behavioral variant typically 


695 


first 
manifests with prominent 
changes in social 
behavior, such as disinhibition, apathy, or 
perseverative behavior, that 
may not 
infrequently lead to a primary psychiatric diagnosis. In 
contrast, the language variant 
of frontotemporal 
NCD may manifest 
with impairments in 
expressive language or word comprehension. 


In major or mild vascular NCD, there is typically a history of stroke temporally related to the 
onset 
of cognitive impairment, and infarcts or hemosiderin deposits observed on brain imaging 
can be judged sufficient 
to account 
for the clinical 
picture. However, major or mild vascular 
NCD shares many clinical 
features with Alzheimer s disease; 
frequently Alzheimer s pathology 
is present 
alone or in combination with vascular pathologies. It 
should be noted that 
white matter 
change alone does not 
constitute enough evidence of cerebrovascular disease to propose a mixed 
etiology if the other diagnostic considerations support 
the diagnosis of NCD due to Alzheimer s 
disease. The presence of subcortical 
ischemic changes on neuroimaging must 
be interpreted 
carefully in view of whether concurrent Alzheimer s pathology is present. 
Other concurrent, 
active 
neurological 
or systemic 
illness. 
Other neurological 
or systemic illness 


should be considered if there is an appropriate temporal 
relationship and severity to account 
for 
the clinical 
picture. At 
the mild NCD level, it 
may be difficult 
to distinguish an Alzheimer s 
disease etiology from 
that 
of another medical 
condition (e.g., thyroid disorders, vitamin B12 


deficiency). 
Major depressive 
disorder. 
Particularly at 
the mild NCD level, the differential 
diagnosis also 
includes major depression. The presence of depression may be associated with reduced daily 
functioning and poor concentration that 
may resemble an NCD, but 
improvement 
with treatment 
of depression may be useful 
in making the distinction. If the symptoms meeting criteria for a 
major depressive episode are judged to be due to the physiological 
effects of Alzheimer s 
disease, a diagnosis of depressive disorder due to Alzheimer s disease, with major depressive  
like episode, should be given instead of major depressive disorder. 


Comorbidity 


Most 
individuals with Alzheimer s disease are elderly and have multiple medical 
conditions that 
can complicate diagnosis and influence the clinical 
course. Major or mild NCD due to 
Alzheimer s disease commonly co-occurs with cerebrovascular disease, which contributes to the 
clinical 
picture. When a comorbid condition contributes to the NCD in an individual 
with 
Alzheimer s disease, then NCD due to multiple etiologies should be diagnosed. 


Major or Mild 
Frontotemporal 
Neurocognitive Disorder 



Diagnostic Criteria 


A. 
The 
criteria 
are 
met 
for major or mild 
neurocognitive 
disorder. 
B. 
The 
disturbance 
has insidious onset 
and 
gradual progression. 
C. 
Either (1) or (2): 
1. 
Behavioral variant: 
a. 
Three 
or more 
of 
the 
following 
behavioral symptoms: 
i. 
Behavioral disinhibition. 
ii. 
Apathy or inertia. 
iii. 
Loss of 
sympathy or empathy. 
696 


iv. 
Perseverative, 
stereotyped 
or compulsive/ritualistic behavior. 
v. 
Hyperorality and 
dietary changes. 
b. 
Prominent 
decline 
in 
social cognition 
and/or executive 
abilities. 
2. 
Language 
variant: 
a. 
Prominent 
decline 
in 
language 
ability, 
in 
the 
form of 
speech 
production, 
word 
finding, 
object 
naming, 
grammar, 
or word 
comprehension. 
D. 
Relative 
sparing 
of 
learning 
and 
memory and 
perceptual-motor function. 
E. 
The 
disturbance 
is not 
better explained 
by cerebrovascular disease, 
another 
neurodegenerative 
disease, 
the 
effects of 
a 
substance, 
or another mental, 
neurological, 
or systemic disorder. 
Probable 
frontotemporal 
neurocognitive 
disorder 
is diagnosed 
if 
either of 
the 
following 
is present; 
otherwise, 
possible 
frontotemporal 
neurocognitive 
disorder 
should 
be 
diagnosed: 


1. 
Evidence 
of 
a 
causative 
frontotemporal neurocognitive 
disorder genetic mutation, 
from either family history or genetic testing. 
2. 
Evidence 
of 
disproportionate 
frontal and/or temporal lobe 
involvement 
from 
neuroimaging. 
Possible 
frontotemporal 
neurocognitive 
disorder 
is diagnosed 
if 
there 
is no 
evidence 
of 
a 
genetic mutation, 
and 
neuroimaging 
has not 
been 
performed. 


Coding 
note 
(see 
coding 
table 
on 
pp. 
682 683): 


For major neurocognitive 
disorder due 
to 
probable 
or possible 
frontotemporal 
degeneration, 
with 
behavioral disturbance, 
code 
first 
G31.09 
frontotemporal 
degeneration, 
followed 
by F02.81. 
For major neurocognitive 
disorder due 
to 
probable 
or possible 
frontotemporal degeneration, 
without 
behavioral disturbance, 
code 
first 
G31.09 
frontotemporal degeneration, 
followed 
by F02.80. 


Note: 
The 
severity specifiers  mild,   moderate,  and 
 severe  cannot 
be 
coded 
for 
major neurocognitive 
disorder but 
should 
still be 
recorded. 



For mild 
neurocognitive 
disorder due 
to 
frontotemporal degeneration, 
code 
G31.84. 
(Note: 
Do 
not 
use 
the 
additional code 
for frontotemporal degeneration. 
 With 
behavioral disturbance  and 
 without 
behavioral disturbance  cannot 
be 
coded 
but 
should 
still be 
recorded.) 


For major or mild 
frontotemporal neurocognitive 
disorder: 
Use 
additional code(s) to 
indicate 
clinically significant 
psychiatric symptoms due 
to 
frontotemporal 
degeneration 
(e.g., 
F06.33 
bipolar and 
related 
disorder due 
to 
frontotemporal 
degeneration, 
with 
manic features; 
F07.0 
personality change 
due 
to 
frontotemporal 
degeneration, 
disinhibited 
type). 


Diagnostic Features 


Major or mild frontotemporal 
neurocognitive disorder (NCD) comprises a number of syndromic 
variants characterized by the progressive development 
of behavioral 
and personality change 
and/or language impairment. The behavioral 
variant 
and two language variants (semantic and 
agrammatic/nonfluent) exhibit 
distinct 
patterns of brain atrophy and some distinctive 
neuropathology. The criteria must 
be met 
for either the behavioral 
or the language variant 
to 
make the diagnosis, but many individuals present with features of both. 


Individuals with behavioral-variant 
major or mild frontotemporal 
NCD present 
with varying 
degrees of apathy or disinhibition. They may lose interest 
in socialization, self-care, and personal 
responsibilities, or display socially inappropriate behaviors. Insight 
is usually impaired, and this 
often delays medical 
consultation. The first 
referral 
is often to a psychiatrist. Individuals may 
develop changes in social style, and in religious and political 


697 


beliefs, with repetitive movements, hoarding, changes in eating behavior, and hyperorality. In 
later stages, loss of sphincter control 
may occur. Cognitive decline is less prominent, and formal 
testing may show relatively few deficits in the early stages. Common neurocognitive symptoms 
are lack of planning and organization, distractibility, and poor judgment. Deficits in executive 
function, such as poor performance on tests of mental 
flexibility, abstract 
reasoning, and 
response inhibition, are present, but 
learning and memory are relatively spared, and perceptual-
motor abilities are almost always preserved in the early stages. 


Individuals with language-variant 
major or mild frontotemporal 
NCD present 
with primary 
progressive aphasia with gradual onset, with two subtypes commonly described: semantic variant 
and agrammatic/nonfluent 
variant; 
each variant 
has distinctive features and corresponding 
neuropathology. A third form 
of progressive language decline, called logopenic progressive 
aphasia, is associated with left 
temporoparietal 
dysfunction and is often caused by Alzheimer s 
disease pathology. 


 Probable  is distinguished from 
 possible  frontotemporal 
NCD by the presence of 
causative genetic factors (e.g., mutations in the gene coding for microtubule-associated protein 
tau) or by the presence of distinctive atrophy or reduced activity in frontotemporal 
regions on 
structural or functional imaging. 


Associated Features 



Extrapyramidal 
features may be prominent 
in some cases, with an overlap with syndromes such 
as progressive supranuclear palsy and corticobasal 
degeneration. Features of motor neuron 
disease may be present 
in some cases (e.g., muscle atrophy, weakness). A subset 
of individuals 
develop visual hallucinations. 


Prevalence 


Major or mild frontotemporal 
NCD is a common cause of early-onset 
NCD in individuals 
younger than 65 years. In international 
studies, population prevalence estimates are in the range 
of 2 31 per 100,000, with overall 
rates generally noted to be equal 
in men and women, although 
variation exists among studies. Approximately 20% 25% of cases of frontotemporal 
NCD occur 
in individuals older than 65 years. Frontotemporal 
NCD accounts for about 
5% of all 
cases of 
dementia in unselected autopsy series. The behavioral 
variant 
is the most 
common presentation 
of NCD due to frontotemporal degeneration, occurring in approximately 60% of cases. 


Development and Course 


Individuals with major or mild frontotemporal 
NCD commonly present 
in their 50s, although the 
age at 
onset 
varies from 
the 20s through the 80s. The disease is gradually progressive, with 
median survival 
being 6 11 years after symptom 
onset 
and 3 4 years after diagnosis. Survival 
is 
shorter and decline is faster in major or mild frontotemporal 
NCD than in typical 
Alzheimer s 
disease. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Approximately 40% of individuals with major or mild frontotemporal 
NCD have a family history of early-onset 
NCD, and approximately 10% show an autosomal 
dominant 
inheritance pattern. A number of genetic factors have been identified, such as 
mutations in the gene encoding the microtubule-associated protein tau (MAPT), the granulin 
gene (GRN), and the C9ORF72 gene (C9orf72). A number of families with causative mutations 
have been identified (see the section  Diagnostic Markers  for this disorder), but 
many 
individuals with known familial 
transmission do not 
have a known mutation. The presence of 
motor neuron disease is associated with a more rapid deterioration. 


698 


Diagnostic Markers 


Computed tomography (CT) or structural 
magnetic resonance imaging (MRI) may show distinct 
patterns of atrophy. In behavioral-variant 
major or mild frontotemporal 
NCD, both frontal 
lobes 
(especially the medial 
frontal 
lobes) and the anterior temporal 
lobes are atrophic. In semantic 
language variant 
major or mild frontotemporal 
NCD, the middle, inferior, and anterior temporal 
lobes are atrophic bilaterally but 
asymmetrically, with the left 
side usually being more affected. 
Nonfluent 
language variant 
major or mild frontotemporal 
NCD is associated with predominantly 
left 
posterior frontal-insular atrophy. Functional 
imaging demonstrates hypoperfusion and/or 
cortical 
hypometabolism 
in the corresponding brain regions, which may be present 
in the early 
stages in the absence of structural 
abnormality. Emerging biomarkers for Alzheimer s disease 



(e.g., cerebrospinal 
fluid amyloid-beta and tau levels, and amyloid imaging) may help in the 
differential diagnosis, but the distinction from Alzheimer s disease can remain difficult. 


In familial 
cases of frontotemporal 
NCD, the identification of genetic mutations may help 
confirm 
the diagnosis. Mutations associated with frontotemporal 
NCD include the genes 
encoding microtubule-associated protein tau (MAPT) and granulin (GRN), C9ORF72, 
transactive response DNA-binding protein of 43 kDa (TDP-43, or TARDBP), valosin-containing 
protein (VCP), chromatin modifying protein 2B 
(CHMP2B), and fused in sarcoma protein 
(FUS). 


Functional 
Consequences of Major or Mild Frontotemporal 
Neurocognitive Disorder 


Because of the relative early age at onset of the disorder, the disorder often affects workplace and 
family life. Because of the involvement 
of language and/or behavior, function is often more 
severely impaired relatively early in the course. For individuals with the behavioral 
variant, prior 
to diagnostic clarification there may be significant 
family disruption, legal 
involvement, and 
problems in the workplace because of socially inappropriate behaviors. The functional 
impairment 
attributable to behavioral 
change and language dysfunction, which can include 
hyperorality, impulsive wandering, and other disinhibited behaviors, may far exceed that 
attributable to the cognitive disturbance and may lead to nursing home placement 
or 
institutionalization. These behaviors can be severely disruptive, even in structured care settings, 
particularly when the individuals are otherwise healthy, nonfrail, and free of other medical 
comorbidities. 


Differential 
Diagnosis 


Other neurocognitive 
disorders. 
Other neurodegenerative diseases may be distinguished from 
major or mild frontotemporal 
NCD by their characteristic features. In major or mild NCD due to 
Alzheimer s disease, decline in learning and memory is an early feature. However, 10% 30% of 
individuals presenting with a syndrome suggestive of major or mild frontotemporal 
NCD are 
found at 
autopsy to have Alzheimer s disease pathology. This occurs more frequently in 
individuals who present 
with progressive dysexecutive syndromes in the absence of behavioral 
changes or movement disorder or in those with the logopenic variant. 


In major or mild NCD with Lewy bodies, core and suggestive features of Lewy bodies must 
be present. In major or mild NCD due to Parkinson s disease, spontaneous parkinsonism 
emerges well 
before the cognitive decline. In major or mild vascular NCD, depending on 
affected brain regions, there may also be loss of executive function and behavioral 
changes such 
as apathy, and this disorder should be considered in the differential 
diagnosis. However, history 
of a cerebrovascular event 
is temporally related to the onset 
of cognitive impairment 
in major or 
mild vascular NCD, and neuroimaging reveals infarctions or white matter lesions sufficient 
to 
account for the clinical picture. 


699 


Other neurological 
conditions. 
Major or mild frontotemporal 
NCD overlaps with progressive 
supranuclear palsy, corticobasal 
degeneration, and motor neuron disease clinically as well 
as 



pathologically. Progressive supranuclear palsy is characterized by supranuclear gaze palsies and 
axial-predominant 
parkinsonism. Pseudobulbar signs may be present, and retropulsion (losing 
balance in a backward direction) is often prominent. Neurocognitive assessment 
shows 
psychomotor slowing, poor working memory, and executive dysfunction. Corticobasal 
degeneration presents with asymmetric rigidity, limb apraxia, postural 
instability, myoclonus, 
alien limb phenomenon, and cortical 
sensory loss. Many individuals with behavioral-variant 
major or mild frontotemporal 
NCD show features of motor neuron disease, which tend to be 
mixed upper and predominantly lower motor neuron disease. 


Other mental 
disorders 
and 
medical 
conditions. 
Behavioral-variant 
major or mild frontotemporal 
NCD may be mistaken for a primary mental 
disorder, such as major depression, bipolar 
disorders, or schizophrenia, and individuals with this variant 
often present 
initially to psychiatry. 
Over time, the development 
of progressive neurocognitive difficulties will 
help to make the 
distinction. A careful 
medical 
evaluation will 
help to exclude treatable causes of NCDs, such as 
metabolic disturbances, nutritional 
deficiencies, and infections. If the symptoms characteristic of 
a primary mental 
disorder (e.g., delusions) are judged to be due to the physiological 
effects of 
frontotemporal 
degeneration, a diagnosis of the appropriate mental 
disorder due to 
frontotemporal 
degeneration should be given instead of the primary psychotic disorder (e.g., 
psychotic disorder due to frontotemporal degeneration, with delusions). 


Major or Mild 
Neurocognitive Disorder With 
Lewy Bodies 


Diagnostic Criteria 


A. 
The 
criteria 
are 
met 
for major or mild 
neurocognitive 
disorder. 
B. 
The 
disorder has an 
insidious onset 
and 
gradual progression. 
C. 
The 
disorder meets a 
combination 
of 
core 
diagnostic features and 
suggestive 
diagnostic features for either probable 
or possible 
neurocognitive 
disorder with 
Lewy bodies. 
For probable 
major or mild 
neurocognitive 
disorder with 
Lewy 
bodies, 
the 
individual has two 
core 
features, 
or one 
suggestive 
feature 
with 
one 
or more 
core 
features. 
For possible 
major or mild 
neurocognitive 
disorder with 
Lewy 
bodies, 
the 
individual has only one 
core 
feature, 
or one 
or more 
suggestive 
features. 


1. 
Core 
diagnostic features: 
a. 
Fluctuating 
cognition 
with 
pronounced 
variations in 
attention 
and 
alertness. 
b. 
Recurrent 
visual hallucinations that 
are 
well formed 
and 
detailed. 
c. 
Spontaneous features of 
parkinsonism, 
with 
onset 
subsequent 
to 
the 
development 
of 
cognitive 
decline. 
2. 
Suggestive 
diagnostic features: 
a. 
Meets criteria 
for rapid 
eye 
movement 
sleep 
behavior disorder. 

b. 
Severe 
neuroleptic sensitivity. 
D. 
The 
disturbance 
is not 
better explained 
by cerebrovascular disease, 
another 
neurodegenerative 
disease, 
the 
effects of 
a 
substance, 
or another mental, 
neurological, 
or systemic disorder. 
Coding 
note 
(see 
coding 
table 
on 
pp. 
682 683): 


For major neurocognitive 
disorder with 
probable 
or possible 
Lewy bodies, 
with 
behavioral disturbance, 
code 
first 
G31.83 
Lewy body disease, 
followed 
by F02.81. 


700 


For major neurocognitive 
disorder with 
probable 
or possible 
Lewy bodies, 
without 
behavioral disturbance, 
code 
first 
G31.83 
Lewy body disease, 
followed 
by F02.80. 
Note: 
The 
severity specifiers  mild,   moderate,  and 
 severe  cannot 
be 
coded 
for 
major neurocognitive 
disorder but 
should 
still be 
recorded. 


For mild 
neurocognitive 
disorder with 
Lewy bodies, 
code 
G31.84. 
(Note: 
Do 
not 
use 
the 
additional code 
for Lewy body disease. 
 With 
behavioral disturbance  and 
 without 
behavioral disturbance  cannot 
be 
coded 
but 
should 
still be 
recorded.) 


For major or mild 
neurocognitive 
disorder with 
Lewy bodies: 
Use 
additional code(s) 
to 
indicate 
clinically significant 
psychiatric symptoms due 
to 
Lewy body disease 
(e.g., 
F06.0 
psychotic disorder due 
to 
Lewy body disease, 
with 
hallucinations; 
F06.31 
depressive 
disorder due 
to 
Lewy body disease, 
with 
depressive 
features). 


Diagnostic Features 


Major neurocognitive disorder with Lewy bodies corresponds to the condition known as 
dementia with Lewy bodies (DLB). The overall 
major or mild neurocognitive disorder with 
Lewy bodies (NCDLB) category includes not 
only progressive cognitive impairment 
(with early 
changes in attention, executive function, and visuoperceptual 
ability, rather than learning and 
memory) but 
also recurrent, complex, visual 
hallucinations; 
and concurrent 
symptoms of rapid 
eye movement 
(REM) sleep behavior disorder (which can be a very early manifestation); 
as well 
as hallucinations in other sensory modalities, apathy, anxiety, depression, and delusions. The 
cognitive symptoms may fluctuate in a pattern that 
can resemble a delirium, for which an 
adequate precipitating factor may or may not 
be found. The variable presentation of NCDLB 
symptoms reduces the likelihood of all 
symptoms being observed in a brief clinic visit 
and 
necessitates a thorough assessment, including caregiver observations. The use of assessment 
scales specifically designed to assess fluctuation may aid in diagnosis. Another core feature is 
spontaneous parkinsonism; 
this can often be relatively mild, and the degree of response to 
levodopa therapy is variable. Up to 25% of individuals with probable NCDLB 
may never 
develop extrapyramidal 
signs, and they are not 
essential 
for diagnosis. The parkinsonism 
must 
be 
distinguished from 
neuroleptic-induced extrapyramidal 
signs. Accurate diagnosis is essential 
to 
safe treatment 
planning, as up to 50% of individuals with NCDLB 
have severe sensitivity to 
neuroleptic drugs, and these medications should be used with extreme caution in individuals 
suspected of having an NCDLB diagnosis. 


The diagnosis of mild NCDLB 
is appropriate for individuals who present 
with the core 



clinical 
features at 
a stage when cognitive or functional 
impairments are not 
of sufficient 
severity 
to fulfill 
criteria for major NCD, particularly if nonamnestic cognitive deficits are prominent. 
However, as for all 
mild NCDs, there will 
often be insufficient 
evidence to justify any single 
etiology, and use of the unspecified diagnosis may be more appropriate. 


Associated Features 


Individuals with NCDLB 
frequently experience repeated falls, syncope, or other transient 
episodes of unresponsiveness. Autonomic dysfunction may be observed, including orthostatic 
hypotension, constipation, and urinary incontinence; 
hypersomnia and hyposmia may also be 
observed. 


Prevalence 


Limited data from 
several 
high-income and low- and middle-income countries show that 
the 
population-based prevalence estimates for NCDLB 
range from 
0% to 1.2% of the general 
elderly 
population, and from 
0% to 9.7% of all 
dementia cases. The mean prevalence of major NCDLB 
was 4.2% of all 
dementias in the community, and in clinic-based studies this increased to 7.5% 
of all dementias. The clinical prevalence of major NCDLB among 


701 


individuals with dementia does not 
appear to be significantly affected by either age or sex. In 
studies from 
the United States and United Kingdom, the pathological 
lesions known as Lewy 
bodies are present 
in 20% 35% of cases of dementia. In a population-based study in Minnesota 
that 
relied on medical 
records, the incidence of NCDLB 
was approximately three times higher in 
men than in women age 65 or older. 


Development and Course 


NCDLB 
is a gradually progressive disorder with insidious onset. However, there is often a 
prodromal 
history of confusional 
episodes (delirium) of acute onset, which may be precipitated 
by illness or surgery. The distinction between NCDLB, in which Lewy bodies are primarily 
limbic in location (with or without 
neocortical 
involvement), and major or mild NCD due to 
Parkinson s disease, which starts in the brain stem, is the order in which the cognitive and motor 
symptoms emerge. In NCDLB, the cognitive decline is manifested early in the course of illness 
(see the section  Differential Diagnosis  for this disorder). 


Onset 
of symptoms is typically observed in individuals ages 50 89, with most 
cases having 
onset 
in individuals in the mid-70s. Disease course may be characterized by occasional 
plateaus 
but 
eventually progresses through severe dementia to death. Average duration of survival 
is 5.5  


7.7 years from the onset of cognitive decline. 
Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Familial 
aggregation may occur, and several 
risk genes have been 
identified; 
but 
in most 
cases of NCDLB, there is no family history. The available studies suggest 
that 
genetic risk factors are as important 
in NCDLB 
as in Alzheimer s disease or Parkinson s 



disease. 


Diagnostic Markers 


Biomarkers indicative of NCDLB 
may be considered to carry diagnostic weight 
equivalent 
to 
core clinical 
features; 
these include low striatal 
dopamine transporter uptake on single photon 
emission computed tomography (SPECT) or positron emission tomography (PET) scan, 
abnormal 
(low uptake) (MIBG) myocardial 
scintigraphy suggesting cardiac sympathetic 
denervation, and polysomnographic confirmation of REM sleep without 
atonia. The associated 
condition REM sleep behavior disorder may be diagnosed through a formal 
sleep study or 
identified by questioning the individual 
or informant 
about 
relevant 
symptoms. The underlying 
neurodegenerative disease is primarily associated with misfolding and aggregation of asynuclein, 
which may be confirmed via postmortem 
histopathological 
examination. 
Neuropsychological 
testing beyond the use of a brief screening instrument 
may be necessary to 
define cognitive deficits clearly. Assessment 
scales developed to measure fluctuation can be 
useful. 


Biomarkers supportive of NCDLB 
but 
with more limited evidence of diagnostic value 
include the following: preservation of medial temporal volume relative to Alzheimer s disease on 
magnetic resonance imaging (MRI), generalized low uptake on SPECT/PET 
perfusion scan with 
reduced occipital 
activity with or without 
the cingulate island sign (sparing of the posterior 
cingulate cortex relative to the precuneus plus cuneus on fluorodeoxyglucose-PET 
imaging), and 
prominent 
slow-wave activity on electroencephalogram 
with periodic fluctuations in the prealpha/
theta range. 


Functional 
Consequences of Major or Mild Neurocognitive Disorder 
With Lewy Bodies 


Individuals with NCDLB 
are more functionally impaired than would be expected for their 
cognitive deficits when contrasted to individuals with other neurodegenerative diseases, 


702 


such as Alzheimer s disease. This is largely a result 
of motor and autonomic impairments, which 
cause problems with toileting, transferring, and eating. Sleep disorders and prominent 
psychiatric 
symptoms may also add to functional 
difficulties. Consequently, the quality of life of individuals 
with NCDLB is often significantly worse than that of individuals with Alzheimer s disease. 


Differential 
Diagnosis 


Major or mild 
neurocognitive 
disorder due 
to 
Parkinson s 
disease. 


The distinction between NCDLB 
and NCD due to Parkinson s disease is based on the timing and sequence of motor symptoms 
and cognitive symptoms. Consensus criteria for DLB 
separate NCDLB 
from 
NCD due to 
Parkinson s disease by specifying that 
for dementia to be attributed to Parkinson s disease, the 
Parkinson s disease diagnosis is present 
for at 
least 
1 year before cognitive decline has reached 
the level 
of major NCD, whereas for NCDLB, the cognitive symptoms may begin before, with, 
or in the absence of parkinsonism. By contrast, expert 
consensus criteria for Parkinson s disease 
propose that 
if cognitive decline occurs prior to a motor diagnosis, the diagnosis of Parkinson s 



disease may still 
be made; 
therefore, a clinician may attribute the cognitive decline to the 
Parkinson s disease and diagnose NCD due to Parkinson s disease. Consequently, the clinician 
may choose to diagnose NCD due to Parkinson s disease or NCDLB 
for individuals with major 
NCD that 
starts either before or within 12 months of Parkinson s disease. In such circumstances, 
the clinician decides which diagnosis is more appropriate. If Parkinson s disease has been 
diagnosed for at 
least 
1 year prior to the onset 
of cognitive symptoms, then both expert 
criteria 
agree that 
NCD due to Parkinson s disease would typically be the appropriate diagnosis. The 
timing and sequence of parkinsonism 
and mild NCD may be particularly difficult 
to determine, 
and unspecified NCD may need to be diagnosed until 
the order of clinical 
progression becomes 
evident. 


Comorbidity 


Lewy body pathology frequently coexists with Alzheimer s disease, transactive response DNA-
binding protein 43 (TDP-43) related pathology, and cerebrovascular disease pathology, 
particularly in the oldest 
age groups. TDP-43 is a protein that 
has been identified as a source of 
the proteinopathies across a range of neurodegenerative disorders, including amyotrophic lateral 
sclerosis and frontotemporal 
degeneration. The presence of multiple pathological 
lesions has 
implications for disease prognosis and may be associated with a more rapid cognitive decline and 
shorter survival time. 


Major or Mild 
Vascular Neurocognitive Disorder 


Diagnostic Criteria 


A. 
The 
criteria 
are 
met 
for major or mild 
neurocognitive 
disorder. 
B. 
The 
clinical features are 
consistent 
with 
a 
vascular etiology, 
as suggested 
by 
either of 
the 
following: 
1. 
Onset 
of 
the 
cognitive 
deficits is temporally related 
to 
one 
or more 
cerebrovascular events. 
2. 
Evidence 
for decline 
is prominent 
in 
complex attention 
(including 
processing 
speed) and 
frontal-executive 
function. 
703 


C. 
There 
is evidence 
of 
the 
presence 
of 
cerebrovascular disease 
from history, 
physical examination, 
and/or neuroimaging 
considered 
sufficient 
to 
account 
for 
the 
neurocognitive 
deficits. 
D. 
The 
symptoms are 
not 
better explained 
by another brain 
disease 
or systemic 
disorder. 
Probable 
vascular neurocognitive 
disorder 
is diagnosed 
if 
one 
of 
the 
following 
is 
present; 
otherwise 
possible 
vascular neurocognitive 
disorder 
should 
be 
diagnosed: 



1. 
Clinical criteria 
are 
supported 
by neuroimaging 
evidence 
of 
significant 
parenchymal injury attributed 
to 
cerebrovascular disease 
(neuroimagingsupported). 
2. 
The 
neurocognitive 
syndrome 
is temporally related 
to 
one 
or more 
documented 
cerebrovascular events. 
3. 
Both 
clinical and 
genetic (e.g., 
cerebral autosomal dominant 
arteriopathy with 
subcortical infarcts and 
leukoencephalopathy) evidence 
of 
cerebrovascular 
disease 
is present. 
Possible 
vascular neurocognitive 
disorder 
is diagnosed 
if 
the 
clinical criteria 
are 
met 
but 
neuroimaging 
is not 
available 
and 
the 
temporal relationship 
of 
the 
neurocognitive 
syndrome 
with 
one 
or more 
cerebrovascular events is not 
established. 


Coding 
note 
(see 
coding 
table 
on 
pp. 
682 683): 


For major neurocognitive 
disorder probably or possibly due 
to 
vascular disease, 
with 


behavioral disturbance, 
code 
F01.51. 
For major neurocognitive 
disorder probably or possibly due 
to 
vascular disease, 
without 
behavioral disturbance, 
code 
F01.50. 


An 
additional medical code 
for the 
vascular disease 
is not 
used. 


Note: 
The 
severity specifiers  mild,   moderate,  and 
 severe  cannot 
be 
coded 
for 
major neurocognitive 
disorder but 
should 
still be 
recorded. 
For mild 
vascular neurocognitive 
disorder, 
code 
G31.84. 
(Note: 
Do 
not 
use 
an 


additional code 
for the 
vascular disease. 
 With 
behavioral disturbance  and 
 without 


behavioral disturbance  cannot 
be 
coded 
but 
should 
still be 
recorded.) 
For major or mild 
vascular neurocognitive 
disorder: 
Use 
additional code(s) to 
indicate 
clinically significant 
psychiatric symptoms due 
to 
the 
cerebrovascular 
disease 
(e.g., 
F06.31 
depressive 
disorder due 
to 
cerebrovascular disease, 
with 
depressive 
features). 


Diagnostic Features 


The diagnosis of major or mild vascular neurocognitive disorder (NCD) requires the 
establishment 
of an NCD (Criterion A) and the determination that 
cerebrovascular disease is the 
dominant 
if not 
exclusive pathology that 
accounts for the cognitive deficits (Criteria B 
and C). 
Vascular etiology may range from 
large vessel 
stroke to microvascular disease; 
the presentation 
is therefore very heterogeneous, stemming from 
the types of vascular lesions and their extent 
and 
location. The lesions may be focal, multifocal, or diffuse and occur in various combinations. 
Pathogenic mechanisms responsible for brain parenchymal 
injury include hypoperfusion and 
hypoxia, oxidative stress and inflammation leading to endothelial 
dysfunction, impairment 
of 
autoregulation, and disruption of neurovascular coupling. 


Many individuals with major or mild vascular NCD present with multiple infarctions, with an 
acute stepwise or fluctuating decline in cognition, and intervening periods of stability and even 
some improvement. Others may 
have gradual 
onset 
with slow progression, a rapid development 
of deficits followed by relative stability, or another complex presentation. Major or mild vascular 



NCD with a gradual 
onset 
and slow progression is generally attributable to small 
vessel 
disease 
leading to lesions in the white matter, basal 
ganglia, or thalamus. The gradual 
progression in 
these cases is often punctuated by acute 


704 


events that 
leave subtle neurological 
deficits. The cognitive deficits in these cases can be 
attributed to disruption of cortical-subcortical 
circuits; 
complex attention, particularly speed of 
information processing, and executive function are likely to be affected. Clinical 
subtypes of 
vascular NCD have been described and include 1) poststroke NCD, manifesting immediately 
after a stroke; 
2) subcortical 
ischemic vascular NCD; 
3) multi-infarct 
(cortical) NCD; 
and 4) 
cortical-subcortical vascular NCD. 


Assessing for the presence of sufficient 
cerebrovascular disease relies on history, physical 
examination, and neuroimaging (Criterion C). Etiological 
certainty requires the demonstration of 
abnormalities on neuroimaging. The lack of neuroimaging can result 
in significant 
diagnostic 
inaccuracy by overlooking  silent  brain infarction and white matter lesions. However, if the 
neurocognitive impairment 
is temporally associated with one or more well-documented strokes, 
a probable diagnosis can be made in the absence of neuroimaging. Clinical 
evidence of 
cerebrovascular disease includes documented history of stroke, with cognitive decline temporally 
associated with the event, or physical 
signs consistent 
with stroke (e.g., hemiparesis; 
pseudobulbar syndrome, visual 
field defect). Neuroimaging (magnetic resonance imaging [MRI] 
or computed tomography [CT]) evidence of cerebrovascular disease comprises one or more of 
the following: 
one or more large vessel 
infarcts or hemorrhages, a strategically placed single 
infarct 
or hemorrhage (e.g., in angular gyrus, thalamus, basal 
forebrain), two or more lacunes 
outside the brain stem, or extensive and confluent 
white matter lesions. The latter is often termed 
small 
vessel 
disease 
or subcortical 
ischemic changes 
on clinical 
neuroimaging evaluations. MRI 
is the preferred mode of neuroimaging, and there has been interest 
in using specialized MRI 
techniques to detect 
cerebral 
microbleeds, cortical 
microinfarcts, dilated perivascular spaces, and 
diffusion-based analyses of white matter tracts and network connectivity. 


For mild vascular NCD, history of a single stroke or extensive white matter disease is 
generally sufficient. For major vascular NCD, two or more strokes, a strategically placed stroke, 
or a combination of white matter disease and one or more lacunes is generally necessary. 
However, the relationship between identifiable vascular pathology in the brain on neuroimaging 
and the cognitive symptoms is imperfect, and clinical 
judgment 
is generally needed to relate the 
vascular lesions to the cognitive syndrome. 


The neurocognitive symptoms must 
not 
be better explained by another medical 
condition or 
mental 
disorder. For example, prominent 
memory deficit 
early in the course might 
suggest 
NCD 
due to Alzheimer s disease, early and prominent 
parkinsonian features would suggest 
NCD due 
to Parkinson s disease, and a close association between onset 
of cognitive and depressive 
symptoms would suggest cognitive impairment as a result of depression. 


A number of expert 
international 
groups have similarly defined and categorized the vascular 
NCDs, with which DSM-5 criteria generally display good correspondence. 


Associated Features 



A 
si 
changes, 
sym 
present 
vascul 


P 


Vascul 
Uni 
ages 
Wi 


dem 
vascul 
(15.0%) 
vascul 
ol 
vascul 
Asi 
fact 
the 
vascul 
Japanese Am 


65 years. Overal 


Devel 


Maj 
exponent 
present 
wi 
pl 
progressi 
ischem 
Afri 
ages. 
soci 
educat 


Ri 


En 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
733 



Personality Disorders 


This chapter 
begins with a general 
definition of personality disorder that 
applies to each of 
the 10 specific personality disorders. A personality disorder 
is an enduring pattern of inner 
experience and behavior that 
deviates markedly from 
the norms and expectations of the 
individual s culture, is pervasive and inflexible, has an onset 
in adolescence or early adulthood, 
is stable over time, and leads to distress or impairment. 


With any ongoing review process, especially one of this complexity, different 
viewpoints 
emerge, and an effort 
was made to accommodate them. Thus, personality disorders are included 
in both Sections II and III. The material 
in Section II represents an update of text 
associated with 
the same criteria found in DSM-5 (which were carried over from 
DSM-IV-TR), whereas Section 
III includes the proposed model 
for personality disorder diagnosis and conceptualization 
developed by the DSM-5 Personality and Personality Disorders Work Group. As this field 
evolves, it 
is hoped that 
both versions will 
serve clinical 
practice and research initiatives, 
respectively. 


The following personality disorders are included in this chapter. 



Paranoid 
personality disorder 
is a pattern of 
distrust 
and suspiciousness such that 
others  
motives are interpreted as 
malevolent. 
Schizoid 
personality disorder 
is a pattern of 
detachment 
from 
social 
relationships and a restricted range of 
emotional 
expression. 
Schizotypalpersonality disorder 
is a pattern of 
acute discomfort 
in close relationships, cognitive or 
perceptual 
distortions, 
and eccentricities of behavior. 
Antisocial 
personality disorder 
is a pattern of 
disregard for, and violation of, the rights of 
others, criminality, impulsivity, 
and a failure to learn from experience. 
Borderline personality disorder 
is a pattern of 
instability in interpersonal 
relationships, self-image, and affects, and 
marked impulsivity. 
Histrionic personality disorder is a pattern of excessive emotionality and attention seeking. 
Narcissistic personality disorder is a pattern of grandiosity, need for admiration, and lack of empathy. 
Avoidant 
personality disorder 
is a pattern of 
social 
inhibition, feelings of 
inadequacy, and hypersensitivity to negative 
evaluation. 
Dependent 
personality disorder 
is a pattern of 
submissive and clinging behavior 
related to an excessive need to be taken 
care of. 
Obsessive-compulsive personality disorder is a pattern of preoccupation with orderliness, perfectionism, and control. 
Personality change due to another medical 
condition 
is a persistent 
personality disturbance that 
is judged to be the direct 
pathophysiological consequence of another medical condition (e.g., frontal lobe lesion). 
Other specified personality disorder 
is a category provided for 
two situations: 
1) 
the individual s personality pattern meets 

734 


the general 
criteria for 
a personality disorder, and traits of 
several 
different 
personality disorders are present, but 
the criteria 
for 
any specific personality disorder 
are not 
met; 
or 
2) 
the individual s personality pattern meets the general 
criteria for 
a 
personality disorder, but 
the individual 
is considered to have a personality disorder 
that 
is not 
included in the DSM-5 
classification (e.g., passive-aggressive personality disorder). Unspecified personality disorder 
is for 
presentations in which 
symptoms characteristic of 
a personality disorder 
are present 
but 
there is insufficient 
information to make a more specific 
diagnosis. 


The personality disorders are grouped into three clusters based on descriptive similarities. 
Cluster A includes paranoid, schizoid, and schizotypal 
personality disorders. Individuals with 
these disorders often appear odd or eccentric. Cluster B includes antisocial, borderline, histrionic, 
and narcissistic personality disorders. Individuals with these disorders often appear dramatic, 
emotional, or erratic. Cluster C 
includes avoidant, dependent, and obsessive-compulsive 
personality disorders. Individuals with these disorders often appear anxious or fearful. It 
should 
be noted that 
this clustering system, although useful 
in some research and educational 
situations, 
has serious limitations and has not 
been consistently validated. For instance, two or more 
disorders from 
different 
clusters, or traits from 
several 
of them, can often co-occur and vary in 
intensity and pervasiveness. 


A review of epidemiological 
studies from 
several 
countries found a median prevalence of 
3.6% for disorders in Cluster A, 4.5% for Cluster B, 2.8% for Cluster C, and 10.5% for any 
personality disorder. Prevalence appears to vary across countries and by ethnicity, raising 
questions about 
true cross-cultural 
variation and about 
the impact 
of diverse definitions and 
diagnostic instruments on prevalence assessments. 


Dimensional Models for Personality Disorders 


The diagnostic approach used in this manual 
represents the categorical 
perspective that 
personality disorders are qualitatively distinct 
clinical 
syndromes. An alternative to the 
categorical 
approach is the dimensional 
perspective that 
personality disorders represent 
maladaptive variants of personality traits that 
merge imperceptibly into normality and into one 
another. See Section III for a full 
description of a dimensional 
model 
for personality disorders. 
The DSM-5 personality disorder clusters (i.e., odd-eccentric, dramatic-emotional, and anxious-
fearful) may also be viewed as dimensions representing spectra of personality dysfunction on a 
continuum 
with other mental 
disorders. The alternative dimensional 
models have much in 
common and together appear to cover the important 
areas of personality dysfunction. Their 
integration, clinical 
utility, and relationship with the personality disorder diagnostic categories 
and various aspects of personality dysfunction continue to be under active investigation. This 
includes research on whether the dimensional 
model 
can clarify the cross-cultural 
prevalence 
variations seen with the categorical model. 


General 
Personality Disorder 



Criteria 


A. 
An 
enduring 
pattern 
of 
inner experience 
and 
behavior that 
deviates markedly 
from the 
expectations of 
the 
individual s culture. 
This pattern 
is manifested 
in 
two 
(or more) of 
the 
following 
areas: 
1. 
Cognition 
(i.e., 
ways of 
perceiving 
and 
interpreting 
self, 
other people, 
and 
events). 
2. 
Affectivity (i.e., 
the 
range, 
intensity, 
lability, 
and 
appropriateness of 
emotional 
response). 
3. 
Interpersonal functioning. 
4. 
Impulse 
control. 
735 


B. 
The 
enduring 
pattern 
is inflexible 
and 
pervasive 
across a 
broad 
range 
of 
personal and 
social situations. 
C. 
The 
enduring 
pattern 
leads to 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
D. 
The 
pattern 
is stable 
and 
of 
long 
duration, 
and 
its onset 
can 
be 
traced 
back at 
least 
to 
adolescence 
or early adulthood. 
E. 
The 
enduring 
pattern 
is not 
better explained 
as a 
manifestation 
or consequence 
of 
another mental disorder. 
F. 
The 
enduring 
pattern 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication) or another medical condition 
(e.g., 
head 
trauma). 
Diagnostic Features 


Personality traits 
are enduring patterns of perceiving, relating to, and thinking about 
the 
environment 
and oneself that 
are exhibited in a wide range of social 
and personal 
contexts. Only 
when personality traits are inflexible and maladaptive and cause significant 
functional 
impairment 
or subjective distress do they constitute personality disorders. The essential 
feature 
of a personality disorder is an enduring pattern of inner experience and behavior that 
deviates 
markedly from 
the norms and expectations of the individual s culture and is manifested in at 
least 
two of the following areas: 
cognition, affectivity, interpersonal 
functioning, or impulse 
control 
(Criterion A). This enduring pattern is inflexible and pervasive across a broad range of 
personal 
and social 
situations (Criterion B) and leads to clinically significant 
distress or 
impairment 
in social, occupational, or other important 
areas of functioning (Criterion C). The 
pattern is stable and of long duration, and its onset 
can be traced back at 
least 
to adolescence or 
early adulthood (Criterion D). The pattern is not 
better explained as a manifestation or 
consequence of another mental 
disorder (Criterion E) and is not 
attributable to the physiological 
effects of a substance (e.g., a drug of abuse, a medication, exposure to a toxin) or another 



medical 
condition (e.g., head trauma) (Criterion F). Specific diagnostic criteria are also provided 
for each of the personality disorders included in this chapter. 


The diagnosis of personality disorders requires an evaluation of the individual s long-term 
patterns of functioning, and the particular personality features must 
be evident 
by early 
adulthood. The personality traits that 
define these disorders must 
also be distinguished from 
characteristics that 
emerge in response to specific situational 
stressors or more transient 
mental 
states (e.g., bipolar, depressive, or anxiety disorders; 
substance intoxication). The clinician 
should assess the stability of personality traits over time and across different 
situations. Although 
a single interview with the individual 
is sometimes sufficient 
for making the diagnosis, it 
is often 
necessary to conduct 
more than one interview and to space these over time. Assessment 
can also 
be complicated by the fact 
that 
the characteristics that 
define a personality disorder may not 
be 
considered problematic by the individual 
(i.e., the traits are often ego-syntonic). To help 
overcome this difficulty, supplementary information from other informants may be helpful. 


Development and Course 


The features of a personality disorder usually become recognizable during adolescence or early 
adult 
life. By definition, a personality disorder is an enduring pattern of thinking, feeling, and 
behaving that 
is relatively stable over time. Some types of personality disorder (notably, 
antisocial 
and borderline personality disorders) tend to become less evident 
or to remit 
with age, 
whereas this appears to be less true for some other types (e.g., obsessive-compulsive and 
schizotypal personality disorders). 


Personality disorder categories may be applied with children or adolescents in those 
relatively unusual 
instances in which the individual s particular maladaptive personality traits 
appear to be pervasive, persistent, and unlikely to be limited to a particular 


736 


developmental 
stage or attributable to another mental 
disorder. It 
should be recognized that 
the traits of a personality disorder that 
appear in childhood will 
often not 
persist 
unchanged into 
adult 
life. For a personality disorder to be diagnosed in an individual 
younger than 18 years, the 
features must 
have been present 
for at 
least 
1 year. The one exception to this is antisocial 
personality disorder, which cannot 
be diagnosed in individuals younger than 18 years. Although, 
by definition, a personality disorder requires an onset 
no later than early adulthood, individuals 
may not 
come to clinical 
attention until 
relatively late in life. A personality disorder may be 
exacerbated following the loss of significant 
supporting persons (e.g., a spouse) or previously 
stabilizing social 
situations (e.g., a job). However, the development 
of a change in personality in 
middle adulthood or later life warrants a thorough evaluation to determine the possible presence 
of a personality change due to another medical 
condition or an unrecognized substance use 
disorder. 


Culture-Related Diagnostic Issues 


Core aspects of personality like emotion regulation and interpersonal 
functioning are influenced 
by culture, which also provides means of protection and assimilation and norms for acceptance 
and denunciation of specific behaviors and personality traits. Judgments about 
personality 



functioning must 
take into account 
the individual s ethnic, cultural, and social 
background. 
Personality disorders should not 
be confused with problems associated with acculturation 
following migration or with the expression of habits, customs, or religious and political 
values 
based on the individual s cultural 
background or context. Behavioral 
patterns that 
appear to be 
rigid and dysfunctional 
aspects of personality disorder may reflect 
instead adaptive responses to 
cultural 
constraints. For example, reliance on an abusive relationship in a small 
community 
where divorce is proscribed may not 
reflect 
pathological 
dependence; 
conscientious political 
protest 
that 
puts friends and family members at 
risk with authorities or in conflict 
with legal 
norms does not 
necessarily reflect 
pathological 
callousness. There are marked variations in the 
recognition and diagnosis of personality disorders across cultural, ethnic, and racialized groups. 
Accuracy of diagnosis can be enhanced by attention to culturally patterned conceptions of self 
and attachment, assessment 
biases resulting from 
clinicians  own cultural 
backgrounds or use of 
diagnostic instruments that 
are not 
normed to the population being assessed, and the impact 
of 
social 
determinants such as poverty, acculturative stress, racism, and discrimination on feelings, 
cognitions, and behaviors. It 
is useful 
for the clinician, especially when evaluating someone from 
a different 
background, to obtain additional 
information from 
informants who are familiar with 
the person s cultural background. 


Sex- and Gender-Related Diagnostic Issues 


Certain personality disorders (e.g., antisocial 
personality disorder) are diagnosed more frequently 
in men. Others (e.g., borderline, histrionic, and dependent 
personality disorders) are diagnosed 
more frequently in women; 
however, in the case of borderline personality disorder, this may be 
due to higher help-seeking among women. Nonetheless, clinicians must 
be cautious not 
to 
overdiagnose or underdiagnose certain personality disorders in women or in men because of 
social 
stereotypes about 
typical 
gender roles and behaviors. There is currently insufficient 
evidence on differences between cis- and transgender individuals with respect 
to the 
epidemiology or clinical presentations of personality disorders to draw meaningful conclusions. 


Differential 
Diagnosis 


Other mental 
disorders 
and 
personality 
traits. 
Many of the specific criteria for the personality 
disorders describe features (e.g., suspiciousness, dependency, insensitivity) that 
are also 
characteristic of episodes of other mental disorders. A personality disorder should 


737 


be diagnosed only when the defining characteristics appeared before early adulthood, are typical 
of the individual s long-term 
functioning, and do not 
occur exclusively during an episode of 
another mental 
disorder. It 
may be particularly difficult 
(and not 
particularly useful) to 
distinguish personality disorders from 
persistent 
mental 
disorders such as persistent 
depressive 
disorder that 
have an early onset 
and an enduring, relatively stable course. Some personality 
disorders may have a  spectrum  relationship to other mental 
disorders (e.g., schizotypal 
personality disorder with schizophrenia; 
avoidant 
personality disorder with social 
anxiety 
disorder) based on phenomenological or biological similarities or familial aggregation. 


Personality disorders must 
be distinguished from 
personality traits that 
do not 
reach the 



threshold for a personality disorder. Personality traits are diagnosed as a personality disorder 
only when they are inflexible, maladaptive, and persisting and cause significant 
functional 
impairment or subjective distress. 


Psychotic 
disorders. 
For the three personality disorders that 
may be related to the psychotic 
disorders (i.e., paranoid, schizoid, and schizotypal), there is an exclusion criterion stating that 
the 
pattern of behavior must 
not 
have occurred exclusively during the course of schizophrenia, a 
bipolar or depressive disorder with psychotic features, or another psychotic disorder. When an 
individual 
has a persistent 
mental 
disorder (e.g., schizophrenia) that 
was preceded by a 
preexisting personality disorder, the personality disorder should also be recorded, followed by 
 premorbid  in parentheses. 


Anxiety 
and 
depressive 
disorders. 
The clinician must 
be cautious in diagnosing personality 
disorders during an episode of a depressive disorder or an anxiety disorder, because these 
conditions may have cross-sectional 
symptom 
features that 
mimic personality traits and may 
make it 
more difficult 
to evaluate retrospectively the individual s long-term 
patterns of 
functioning. 


Posttraumatic 
stress 
disorder. 
When personality changes emerge and persist 
after an individual 
has been exposed to extreme stress, a diagnosis of posttraumatic stress disorder should be 
considered. 


Substance 
use 
disorders. 
When an individual 
has a substance use disorder, it 
is important 
not 
to 
make a personality disorder diagnosis based solely on behaviors that 
are consequences of 
substance intoxication or withdrawal 
or that 
are associated with activities in the service of 
sustaining substance use (e.g., antisocial behavior). 
Personality 
change 
due 
to 
another medical 
condition. 
When enduring changes in personality arise as 


a result 
of the physiological 
effects of another medical 
condition (e.g., brain tumor), a diagnosis 
of personality change due to another medical condition should be considered. 


Cluster A Personality Disorders 


Paranoid 
Personality Disorder 


Diagnostic Criteria 
F60.0 


A. 
A 
pervasive 
distrust 
and 
suspiciousness of 
others such 
that 
their motives are 
interpreted 
as malevolent, 
beginning 
by early adulthood 
and 
present 
in 
a 
variety 
of 
contexts, 
as indicated 
by four (or more) of 
the 
following: 
738 


1. 
Suspects, 
without 
sufficient 
basis, 
that 
others are 
exploiting, 
harming, 
or 
deceiving 
him or her. 

2. 
Is preoccupied 
with 
unjustified 
doubts about 
the 
loyalty or trustworthiness of 
friends or associates. 
3. 
Is reluctant 
to 
confide 
in 
others because 
of 
unwarranted 
fear that 
the 
information 
will be 
used 
maliciously against 
him or her. 
4. 
Reads hidden 
demeaning 
or threatening 
meanings into 
benign 
remarks or 
events. 
5. 
Persistently bears grudges (i.e., 
is unforgiving 
of 
insults, 
injuries, 
or slights). 
6. 
Perceives attacks on 
his or her character or reputation 
that 
are 
not 
apparent 
to 
others and 
is quick to 
react 
angrily or to 
counterattack. 
7. 
Has recurrent 
suspicions, 
without 
justification, 
regarding 
fidelity of 
spouse 
or 
sexual partner. 
B. 
Does not 
occur exclusively during 
the 
course 
of 
schizophrenia, 
a 
bipolar disorder 
or depressive 
disorder with 
psychotic features, 
or another psychotic disorder and 
is not 
attributable 
to 
the 
physiological effects of 
another medical condition. 
Note: 
If 
criteria 
are 
met 
prior to 
the 
onset 
of 
schizophrenia, 
add 
 premorbid,  i.e., 
 paranoid 
personality disorder (premorbid).  


Diagnostic Features 


The essential 
feature of paranoid personality disorder is a pattern of pervasive distrust 
and 
suspiciousness of others such that their motives are interpreted as malevolent. This pattern begins 
by early adulthood and is present in a variety of contexts. 


Individuals with this disorder assume that 
other people will 
exploit, harm, or deceive them, 
even if no evidence exists to support 
this expectation (Criterion A1). They suspect 
on the basis of 
little or no evidence that 
others are plotting against 
them 
and may attack them 
suddenly, at 
any 
time and without 
reason. They often feel 
that 
they have been deeply and irreversibly injured by 
another person or persons even when there is no objective evidence for this. They are 
preoccupied with unjustified doubts about 
the loyalty or trustworthiness of their friends and 
associates, whose actions are minutely scrutinized for evidence of hostile intentions (Criterion 
A2). Any perceived deviation from 
trustworthiness or loyalty serves to support 
their underlying 
assumptions. They are so amazed when a friend or associate shows loyalty that 
they cannot 
trust 
or believe it. If they get 
into trouble, they expect 
that 
friends and associates will 
either attack or 
ignore them. 


Individuals with paranoid personality disorder are reluctant 
to confide in or become close to 
others because they fear that 
the 
information they share will 
be used against 
them 
(Criterion A3). 
They may refuse to answer personal 
questions, saying that 
the information is  nobody s 
business.  They read hidden meanings that 
are demeaning and threatening into benign remarks 
or events (Criterion A4). For example, an individual 
with this disorder may misinterpret 
an 
honest 
mistake by a store clerk as a deliberate attempt 
to shortchange, or view a casual 
humorous 
remark by a coworker as a serious character attack. Compliments are often misinterpreted (e.g., a 
compliment on a new acquisition is misinterpreted as a criticism for selfishness; a compliment on 
an accomplishment 
is misinterpreted as an attempt 
to coerce more and better performance). They 
may view an offer of help as a criticism that they are not doing well enough on their own. 



Individuals with this disorder persistently bear grudges and are unwilling to forgive the 
insults, injuries, or slights that 
they think they have received (Criterion A5). Minor slights arouse 
major hostility, and the hostile feelings persist 
for a long time. Because they are constantly 
vigilant 
to the harmful 
intentions of others, they very often feel 
that 
their character or reputation 
has been attacked or that 
they have been slighted in some other way. They are quick to 
counterattack and react 
with anger to perceived insults (Criterion A6). Individuals with this 
disorder may be pathologically jealous, often suspecting that their spouse 


739 


or sexual 
partner is unfaithful 
without 
any adequate justification (Criterion A7). They may 
gather trivial 
and circumstantial 
 evidence  to support 
their jealous beliefs. They want 
to 
maintain complete control 
of intimate relationships to avoid being betrayed and may constantly 
question and challenge the whereabouts, actions, intentions, and fidelity of their spouse or 
partner. 


Paranoid personality disorder should not 
be diagnosed if the pattern of behavior occurs 
exclusively during the course of schizophrenia, a bipolar disorder or depressive disorder with 
psychotic features, or another psychotic disorder, or if it 
is attributable to the physiological 
effects of a neurological 
(e.g., temporal 
lobe epilepsy) or another medical 
condition (Criterion 
B). 


Associated Features 


Individuals with paranoid personality disorder are generally difficult 
to get 
along with and often 
have problems with close relationships. Their excessive suspiciousness and hostility may be 
expressed in overt 
argumentativeness, in recurrent 
complaining, or by hostile aloofness. They 
display a labile range of affect, with hostile, stubborn, and sarcastic expressions predominating. 
Their combative and suspicious nature may elicit 
a hostile response in others, which then serves 
to confirm their original expectations. 


Because individuals with paranoid personality disorder lack trust 
in others, they need to have 
a high degree of control 
over those around them. They are often rigid, critical 
of others, and 
unable to collaborate, although they have great 
difficulty accepting criticism 
themselves. They 
may blame others for their own shortcomings. Because of their quickness to counterattack in 
response to the threats they perceive around them, they may be litigious and frequently become 
involved in legal 
disputes. Individuals with this disorder seek to confirm 
their preconceived 
negative notions regarding people or situations they encounter, attributing malevolent 
motivations to others that 
are projections of their own fears. They may exhibit 
thinly hidden, 
unrealistic grandiose fantasies, are often attuned to issues of power and rank, and tend to develop 
negative stereotypes of others, particularly those from 
population groups distinct 
from 
their own. 
Attracted by simplistic formulations of the world, they are often wary of ambiguous situations. 
They may be perceived as  fanatics  and form 
tightly knit 
 cults  or groups with others who 
share their paranoid belief systems. 


Prevalence 


The estimated prevalence of paranoid personality based on a probability subsample from 
Part 
II 



of the National 
Comorbidity Survey Replication was 2.3%. The prevalence of paranoid 
personality disorder in the National 
Epidemiologic Survey on Alcohol 
and Related Conditions 
was 4.4%. A review of six epidemiological 
studies (four in the United States) found a median 
prevalence of 3.2%. In forensic settings, the estimated prevalence may be as high as 23%. 


Development and Course 


Paranoid personality disorder may be first 
apparent 
in childhood and adolescence with 
solitariness, poor peer relationships, social 
anxiety, underachievement 
in school, and 
interpersonal 
hypersensitivity. Adolescent 
onset 
of paranoid personality disorder is associated 
with a prior history of childhood maltreatment, externalizing symptoms, bullying of peers, and 
adult appearance of interpersonal aggression. 


Risk and Prognostic Factors 


Environmental. 
Exposure to social 
stressors such as socioeconomic inequality, marginalization, 
and racism is associated with decreased trust, which in some cases is adaptive. 


740 


The combination of social 
stress and childhood maltreatment 
accounts for the increased 
prevalence of paranoid symptoms in social 
groups facing racial 
discrimination. Both longitudinal 
and cross-sectional 
studies confirm 
that 
childhood trauma is a risk factor for paranoid personality 
disorder. 


Genetic 
and 
physiological. 
There is some evidence for an increased prevalence of paranoid 
personality disorder in relatives of probands with schizophrenia and for a more specific familial 
relationship with delusional disorder, persecutory type. 


Culture-Related Diagnostic Issues 


Some behaviors that 
are influenced by sociocultural 
contexts or specific life circumstances may 
be erroneously labeled paranoid and may even be reinforced by the process of clinical 
evaluation. Migrants, members of socially oppressed ethnic and racialized populations, and other 
groups facing social 
adversity, racism, and discrimination may display guarded or defensive 
behaviors because of unfamiliarity (e.g., language barriers or lack of knowledge of rules and 
regulations) or in response to the neglect, hostility, or indifference of the majority society. Some 
cultural 
groups develop low generalized trust, especially of outgroup members, which may lead 
to behaviors that 
can be misjudged as paranoid. These include guardedness, limited outward 
emotionality, cognitive rigidity, social 
distance, and hostility or defensiveness in situations 
experienced as unfair or discriminatory. These behaviors can, in turn, generate anger and 
frustration in others, including clinicians, thus setting up a vicious cycle of mutual 
mistrust, 
which should not be confused with paranoid traits or paranoid personality disorder. 


Sex- and Gender-Related Diagnostic Issues 


While paranoid personality disorder was found to be more common in men than in women in a 
meta-analysis relying on clinical 
and community samples, the National 
Epidemiologic Survey on 



Alcohol and Related Conditions found it to be more common in women. 


Differential 
Diagnosis 


Other mental 
disorders 
with 
psychotic 
symptoms. 
Paranoid personality disorder can be distinguished 
from 
delusional 
disorder, persecutory type; 
schizophrenia; 
and a bipolar or depressive disorder 
with psychotic features because these disorders are all 
characterized by a period of persistent 
psychotic symptoms (e.g., delusions and hallucinations). For an additional 
diagnosis of paranoid 
personality disorder to be given, the personality disorder must 
have been present 
before the onset 
of psychotic symptoms and must 
persist 
when the psychotic symptoms are in remission. When 
an individual 
has another persistent 
mental 
disorder (e.g., schizophrenia) that 
was preceded by 
paranoid personality disorder, paranoid personality disorder should also be recorded, followed by 
 premorbid  in parentheses. 
Personality 
change 
due 
to 
another medical 
condition. 
Paranoid personality disorder must 
be 


distinguished from 
personality change due to another medical 
condition, in which the traits that 


emerge are a direct physiological consequence of another medical condition. 
Substance 
use 
disorders. 
Paranoid personality disorder must 
be distinguished from 
symptoms that 
may develop in association with persistent substance use. 
Paranoid 
traits 
associated 
with 
physical 
handicaps. 
The disorder must 
also be distinguished from 


paranoid traits associated with the development 
of physical 
handicaps (e.g., a hearing 
impairment). 


741 


Other personality 
disorders 
and 
personality 
traits. 
Other personality disorders may be confused with 
paranoid personality disorder because they have certain features in common. It 
is therefore 
important 
to distinguish among these disorders based on differences in their characteristic 
features. However, if an individual 
has personality features that 
meet 
criteria for one or more 
personality disorders in addition to paranoid personality disorder, all 
can be diagnosed. Paranoid 
personality disorder and schizotypal 
personality disorder share the traits of suspiciousness, 
interpersonal 
aloofness, and paranoid ideation, but 
schizotypal 
personality disorder also includes 
symptoms such as magical 
thinking, unusual 
perceptual 
experiences, and odd thinking and 
speech. Individuals with behaviors that 
meet 
criteria for schizoid personality disorder are often 
perceived as strange, eccentric, cold, and aloof, but 
they do not 
usually have prominent 
paranoid 
ideation. The tendency of individuals with paranoid personality disorder to react 
to minor stimuli 
with anger is also seen in borderline and histrionic personality disorders. However, these 
disorders are not 
necessarily associated with pervasive suspiciousness, and borderline personality 
disorder exhibits higher levels of impulsivity and self-destructive behavior. People with avoidant 
personality disorder may also be reluctant 
to confide in others, but 
more from 
fear of being 
embarrassed or found inadequate than from 
fear of others  malicious intent. Although antisocial 
behavior may be present 
in some individuals with paranoid personality disorder, it 
is not 
usually 
motivated by a desire for personal 
gain or to exploit 
others as in antisocial 
personality disorder, 
but 
rather is more often attributable to a desire for revenge. Individuals with narcissistic 
personality disorder may occasionally display suspiciousness, social 
withdrawal, or alienation, 
but this derives primarily from fears of having their imperfections or flaws revealed. 



Paranoid traits may be adaptive, particularly in threatening environments. Paranoid 
personality disorder should be diagnosed only when these traits are inflexible, maladaptive, and 
persisting and cause significant functional impairment or subjective distress. 


Comorbidity 


Particularly in response to stress, individuals with this disorder may experience very brief 
psychotic episodes (lasting minutes to hours). In some instances, paranoid personality disorder 
may appear as the premorbid antecedent 
of delusional 
disorder or schizophrenia. Individuals 
with paranoid personality disorder may develop major depressive disorder and may be at 
increased risk for agoraphobia and obsessive-compulsive disorder. Alcohol 
and other substance 
use disorders frequently occur. The most 
common co-occurring personality disorders appear to 
be schizotypal, schizoid, narcissistic, avoidant, and borderline. 


Schizoid 
Personality Disorder 


Diagnostic Criteria 
F60.1 


A. 
A 
pervasive 
pattern 
of 
detachment 
from social relationships and 
a 
restricted 
range 
of 
expression 
of 
emotions in 
interpersonal settings, 
beginning 
by early 
adulthood 
and 
present 
in 
a 
variety of 
contexts, 
as indicated 
by four (or more) of 
the 
following: 
1. 
Neither desires nor enjoys close 
relationships, 
including 
being 
part 
of 
a 
family. 
2. 
Almost 
always chooses solitary activities. 
3. 
Has little, 
if 
any, 
interest 
in 
having 
sexual experiences with 
another person. 
4. 
Takes pleasure 
in 
few, 
if 
any, 
activities. 
5. 
Lacks close 
friends or confidants other than 
first-degree 
relatives. 
742 


6. 
Appears indifferent 
to 
the 
praise 
or criticism of 
others. 
7. 
Shows emotional coldness, 
detachment, 
or flattened 
affectivity. 
B. 
Does not 
occur exclusively during 
the 
course 
of 
schizophrenia, 
a 
bipolar disorder 
or depressive 
disorder with 
psychotic features, 
another psychotic disorder, 
or 
autism spectrum disorder and 
is not 
attributable 
to 
the 
physiological effects of 
another medical condition. 
Note: If 
criteria 
are 
met 
prior to 
the 
onset 
of 
schizophrenia, 
add 
 premorbid,  i.e., 
 schizoid 
personality disorder (premorbid).  


Diagnostic Features 



The essential 
feature of schizoid personality disorder is a pervasive pattern of detachment 
from 
social 
relationships and a restricted range of expression of emotions in interpersonal 
settings. 
This pattern begins by early adulthood and is present in a variety of contexts. 


Individuals with schizoid personality disorder appear to lack a desire for intimacy, seem 
indifferent 
to opportunities to develop close relationships, and do not 
seem 
to derive much 
satisfaction from 
being part 
of a family or other social 
group (Criterion A1). They prefer 
spending time by themselves, rather than being with other people. They often appear to be 
socially isolated or  loners  and almost 
always choose solitary activities or hobbies that 
do not 
include interaction with others (Criterion A2). They prefer mechanical 
or abstract 
tasks, such as 
computer or mathematical 
games. They may have very little interest 
in having sexual 
experiences with another person (Criterion A3) and take pleasure in few, if any, activities 
(Criterion A4). There is usually a reduced experience of pleasure from 
sensory, bodily, or 
interpersonal 
experiences, such as walking on a beach at 
sunset 
or having sex. These individuals 
have no close friends or confidants, except possibly a first-degree relative (Criterion A5). 


Individuals with schizoid personality disorder often seem 
indifferent 
to the approval 
or 
criticism 
of others and do not 
appear to be bothered by what 
others may think of them 
(Criterion 
A6). They may be oblivious to the normal 
subtleties of social 
interaction and often do not 
respond appropriately to social 
cues so that 
they seem 
socially inept 
or superficial 
and self-
absorbed. They usually display a  bland  exterior without 
visible emotional 
reactivity and rarely 
reciprocate gestures or facial 
expressions, such as smiles or nods (Criterion A7). They claim 
that 
they rarely experience strong emotions such as anger and joy. They often display a constricted 
affect 
and appear cold and aloof. However, in those very unusual 
circumstances in which these 
individuals become at 
least 
temporarily comfortable in revealing themselves, they may 
acknowledge having painful feelings, particularly related to social interactions. 


Schizoid personality disorder should not 
be diagnosed if the pattern of behavior occurs 
exclusively during the course of schizophrenia, a bipolar or depressive disorder with psychotic 
features, another psychotic disorder, or autism 
spectrum 
disorder, or if it 
is attributable to the 
physiological 
effects of a neurological 
(e.g., temporal 
lobe epilepsy) or another medical 
condition (Criterion B). 


Associated Features 


Individuals with schizoid personality disorder may have particular difficulty expressing anger, 
even in response to direct 
provocation, which contributes to the impression that 
they lack 
emotion. Their lives sometimes seem 
directionless, and they may appear to  drift  in their goals. 
Such individuals often react 
passively to adverse circumstances and have difficulty responding 
appropriately to important 
life events. Because of their lack of social 
skills and lack of desire for 
sexual 
experiences, individuals with this disorder have few friendships, date infrequently, and 
often do not 
marry. Occupational 
functioning may be impaired, particularly if interpersonal 
involvement 
is required, but 
individuals with this disorder may do well 
when they work under 
conditions of social isolation. 


743 


Prevalence 



Schizoid personality disorder is uncommon in clinical 
settings. The estimated prevalence of 
schizoid personality disorder based on a probability subsample from 
Part 
II of the National 
Comorbidity Survey Replication was 4.9%. The prevalence of schizoid personality disorder in 
the National 
Epidemiologic Survey on Alcohol 
and Related Conditions was 3.1%. A review of 
six epidemiological studies (four in the United States) found a median prevalence of 1.3%. 


Development and Course 


Schizoid personality disorder may be first 
apparent 
in childhood and adolescence with 
solitariness, poor peer relationships, and underachievement 
in school, which mark these children 
or adolescents as different and make them subject to teasing. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Schizoid personality disorder may have increased prevalence in the 
relatives of individuals with schizophrenia or schizotypal personality disorder. 


Culture-Related Diagnostic Issues 


Individuals from 
a variety of cultural 
backgrounds sometimes exhibit 
defensive behaviors and 
interpersonal 
styles that 
may be erroneously labeled as  schizoid.  For example, those who have 
moved from 
rural 
to metropolitan environments may react 
with  emotional 
freezing  that 
may 
last 
for several 
months and manifest 
as solitary activities, constricted affect, and other deficits in 
communication. Immigrants from 
other countries are sometimes mistakenly perceived as cold, 
hostile, or indifferent, which may be a response to social ostracism from the host society. 


Sex- and Gender-Related Diagnostic Issues 


While some research suggests that 
schizoid personality disorder may be more common in men, 
other research suggests that there is no gender difference in prevalence. 


Differential 
Diagnosis 


Other mental 
disorders 
with 
psychotic 
symptoms. 
Schizoid personality disorder can be distinguished 
from 
delusional 
disorder, schizophrenia, and a bipolar or depressive disorder with psychotic 
features because these disorders are all 
characterized by a period of persistent 
psychotic 
symptoms (e.g., delusions and hallucinations). To give an additional 
diagnosis of schizoid 
personality disorder, the personality disorder must 
have been present 
before the onset 
of 
psychotic symptoms and must 
persist 
when the psychotic symptoms are in remission. When an 
individual 
has a persistent 
psychotic disorder (e.g., schizophrenia) that 
was preceded by schizoid 
personality disorder, schizoid personality disorder should also be recorded, followed by 
 premorbid  in parentheses. 


Autism spectrum disorder. 
There may be great 
difficulty differentiating individuals with schizoid 
personality disorder from 
individuals with autism 
spectrum 
disorder, particularly with milder 
forms of either disorder, as both include a seeming indifference to companionship with others. 
However, autism spectrum disorder may be differentiated by stereotyped behaviors and interests. 
Personality 
change 
due 
to 
another medical 
condition. 
Schizoid personality disorder must 
be 



distinguished from 
personality change due to another medical 
condition, in which the traits that 
emerge are a direct physiological consequence of another medical condition. 


744 


Substance 
use 
disorders. 
Schizoid personality disorder must 
also be distinguished from 
symptoms 
that may develop in association with persistent substance use. 
Other personality 
disorders 
and 
personality 
traits. 
Other personality disorders may be confused with 


schizoid personality disorder because they have certain features in common. It 
is, therefore, 
important 
to distinguish among these disorders based on differences in their characteristic 
features. However, if an individual 
has personality features that 
meet 
criteria for one or more 
personality disorders in addition to schizoid personality disorder, all 
can be diagnosed. Although 
characteristics of social 
isolation and restricted affectivity are common to schizoid, schizotypal, 
and paranoid personality disorders, schizoid personality disorder can be distinguished from 
schizotypal 
personality disorder by the lack of cognitive and perceptual 
distortions and from 
paranoid personality disorder by the lack of suspiciousness and paranoid ideation. The social 
isolation of schizoid personality disorder can be distinguished from 
that 
of avoidant 
personality 
disorder, which is attributable to fear of being embarrassed or found inadequate and excessive 
anticipation of rejection. In contrast, people with schizoid personality disorder have a more 
pervasive detachment 
and limited desire for social 
intimacy. Individuals with obsessive-
compulsive personality disorder may also show an apparent 
social 
detachment 
stemming from 
devotion to work and discomfort 
with emotions, but 
they do have an underlying capacity for 
intimacy. 


Individuals who are  loners  or quite introverted may display personality traits that 
might 
be 
considered schizoid, consistent 
with the broader conceptualization of schizoid personality 
disorder as a disorder defined by pathological 
introversion/detachment. Only when these traits 
are inflexible and maladaptive and cause significant 
functional 
impairment 
or subjective distress 
do they constitute schizoid personality disorder. 


Comorbidity 


Particularly in response to stress, individuals with this disorder may experience very brief 
psychotic episodes (lasting minutes to hours). In some instances, schizoid personality disorder 
may appear as the premorbid antecedent 
of delusional 
disorder or schizophrenia. Individuals 
with this disorder may sometimes develop major depressive disorder. Schizoid personality 
disorder most often co-occurs with schizotypal, paranoid, and avoidant personality disorders. 


Schizotypal 
Personality Disorder 


Diagnostic Criteria 
F21 


A. 
A 
pervasive 
pattern 
of 
social and 
interpersonal deficits marked 
by acute 
discomfort 
with, 
and 
reduced 
capacity for, 
close 
relationships as well as by 

cognitive 
or perceptual distortions and 
eccentricities of 
behavior, 
beginning 
by 
early adulthood 
and 
present 
in 
a 
variety of 
contexts, 
as indicated 
by five 
(or 
more) of 
the 
following: 


1. 
Ideas of 
reference 
(excluding 
delusions of 
reference). 
2. 
Odd 
beliefs or magical thinking 
that 
influences behavior and 
is inconsistent 
with 
subcultural norms (e.g., 
superstitiousness, 
belief 
in 
clairvoyance, 
telepathy, 
or  sixth 
sense ; 
in 
children 
and 
adolescents, 
bizarre 
fantasies or 
preoccupations). 
3. 
Unusual perceptual experiences, 
including 
bodily illusions. 
4. 
Odd 
thinking 
and 
speech 
(e.g., 
vague, 
circumstantial, 
metaphorical, 
overelaborate, 
or stereotyped). 
5. 
Suspiciousness or paranoid 
ideation. 
6. 
Inappropriate 
or constricted 
affect. 
745 


7. 
Behavior or appearance 
that 
is odd, 
eccentric, 
or peculiar. 
8. 
Lack of 
close 
friends or confidants other than 
first-degree 
relatives. 
9. 
Excessive 
social anxiety that 
does not 
diminish 
with 
familiarity and 
tends to 
be 
associated 
with 
paranoid 
fears rather than 
negative 
judgments about 
self. 
B. 
Does not 
occur exclusively during 
the 
course 
of 
schizophrenia, 
a 
bipolar disorder 
or depressive 
disorder with 
psychotic features, 
another psychotic disorder, 
or 
autism spectrum disorder. 
Note: 
If 
criteria 
are 
met 
prior to 
the 
onset 
of 
schizophrenia, 
add 
 premorbid,  e.g., 
 schizotypal personality disorder (premorbid).  


Diagnostic Features 


The essential 
feature of schizotypal 
personality disorder is a pervasive pattern of social 
and 
interpersonal 
deficits marked by acute discomfort 
with, and reduced capacity for, close 
relationships as well 
as by cognitive or perceptual 
distortions and eccentricities of behavior. This 
pattern begins by early adulthood and is present in a variety of contexts. 


Individuals with schizotypal 
personality disorder often have ideas of reference (i.e., incorrect 
interpretations of casual 
incidents and external 
events as having a particular and unusual 
meaning specifically for the person) (Criterion A1). These should be distinguished from 
delusions of reference, in which the beliefs are held with 
delusional 
conviction. These 
individuals may be superstitious or preoccupied with paranormal 
phenomena that 
are outside the 
norms of their subculture (Criterion A2). They may feel 
that 
they have special 
powers to sense 
events before they happen or to read others  thoughts. They may believe that 
they have magical 
control 
over others, which can be implemented directly (e.g., believing that 
their spouse s taking 
the dog out 
for a walk is the direct 
result 
of thinking an hour earlier it 
should be done) or 
indirectly through compliance with magical 
rituals (e.g., walking past 
a specific object 
three 
times to avoid a certain harmful 
outcome). Perceptual 
alterations may be present 
(e.g., sensing 



that 
another person is present 
or hearing a voice murmuring their name) (Criterion A3). Their 
speech may include unusual 
or idiosyncratic phrasing and construction. It 
is often loose, 
digressive, or vague, but 
without 
actual 
derailment 
or incoherence (Criterion A4). Responses can 
be either overly concrete or overly abstract, and words or concepts are sometimes applied in 
unusual ways (e.g., the individual may state that he or she was not  talkable  at work). 


Individuals with this disorder are often suspicious and may have paranoid ideation (e.g., 
believing their colleagues at 
work are intent 
on undermining their reputation with the boss) 
(Criterion A5). They are usually not 
able to negotiate the full 
range of affects and interpersonal 
cuing required for successful 
relationships and thus often appear to interact 
with others in an 
inappropriate, stiff, or constricted fashion (Criterion A6). These individuals are often considered 
to be odd or eccentric because of unusual 
mannerisms, an often unkempt 
manner of dress that 
does not 
quite  fit 
together,  and inattention to the usual 
social 
conventions (e.g., the individual 
may avoid eye contact, wear clothes that 
are ink stained and ill-fitting, and be unable to join in 
the give-and-take banter of co-workers) (Criterion A7). 


Individuals with schizotypal 
personality disorder experience interpersonal 
relatedness as 
problematic and are uncomfortable relating to other people. Although they may express 
unhappiness about 
their lack of relationships, their behavior suggests a decreased desire for 
intimate contacts. As a result, they usually have no or few close friends or confidants other than a 
first-degree relative (Criterion A8). They are anxious in social 
situations, particularly those 
involving unfamiliar people (Criterion A9). They will 
interact 
with other individuals when they 
have to but 
prefer to keep to themselves because they feel 
that 
they are different 
and just 
do not 
 fit 
in.  Their social 
anxiety does not 
easily abate, even when they spend more time in the setting 
or become more familiar with the other people, because their anxiety tends to be associated with 
suspiciousness regarding others  motivations. For example, when attending a dinner party, the 
individual with schizotypal 


746 


personality disorder will 
not 
become more relaxed as time goes on, but 
rather may become 
increasingly tense and suspicious. 


Schizotypal 
personality disorder should not 
be diagnosed if the pattern of behavior occurs 
exclusively during the course of schizophrenia, a bipolar or depressive disorder with psychotic 
features, another psychotic disorder, or autism spectrum disorder (Criterion B). 


Associated Features 


Individuals with schizotypal 
personality disorder often seek treatment 
for the associated 
symptoms of anxiety or depression rather than for the personality disorder features per se. 


Prevalence 


The estimated prevalence of schizotypal 
personality disorder based on a probability subsample 
from 
Part 
II of 
the National 
Comorbidity Survey Replication was 3.3%.The prevalence of 
schizotypal 
personality disorder in the National 
Epidemiologic Survey on Alcohol 
and Related 
Conditions data was 3.9%. A review of five epidemiological 
studies (three in the United States) 
found a median prevalence of 0.6%. 



Development and Course 


Schizotypal 
personality disorder has a relatively stable course, with only a small 
proportion of 
individuals going on to develop schizophrenia or another psychotic disorder. Schizotypal 
personality disorder may be first 
apparent 
in childhood and adolescence with solitariness, poor 
peer relationships, social 
anxiety, underachievement 
in school, hypersensitivity, peculiar 
thoughts and language, and bizarre fantasies. These children may appear  odd  or  eccentric  
and attract teasing. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Schizotypal 
personality disorder appears to aggregate familially and is 
more prevalent 
among the first-degree biological 
relatives of individuals with schizophrenia than 
among the general 
population. There may also be a modest 
increase in schizophrenia and other 
psychotic disorders in the relatives of probands with schizotypal 
personality disorder. Twin 
studies indicate highly stable genetic factors and rather transient 
environmental 
factors for an 
increased risk for the schizotypal 
syndrome, and genetic risk variants for schizophrenia may be 
linked to schizotypal 
personality disorder. Neuroimaging studies detect 
group-level 
differences 
in the size and function of specific brain regions in individuals with schizotypal 
personality 
disorder in comparison with healthy persons, individuals with schizophrenia, and individuals 
with other personality disorders. 


Culture-Related Diagnostic Issues 


Cognitive and perceptual 
distortions must 
be evaluated in the context 
of the individual s cultural 
milieu. Pervasive culturally determined characteristics, particularly those regarding supernatural 
and religious beliefs and practices (life beyond death, speaking in tongues, voodoo, shamanism, 
mind reading, sixth sense, evil 
eye, magical 
beliefs related to health and illness), can appear to be 
schizotypal 
to the uninformed clinician. Thus, observed cross-national 
and cross-ethnic 
variations in the prevalence and expression of schizotypal 
traits may be a true epidemiological 
finding or one due to differences in the cultural acceptance of these experiences. 


Sex- and Gender-Related Diagnostic Issues 


Schizotypal personality disorder appears to be slightly more common in men than in women. 


747 


Differential 
Diagnosis 


Other mental 
disorders 
with 
psychotic 
symptoms. 
Schizotypal 
personality disorder can be 
distinguished from 
delusional 
disorder, schizophrenia, and a bipolar or depressive disorder with 
psychotic features because these disorders are all 
characterized by a period of persistent 
psychotic symptoms (e.g., delusions and hallucinations). To give an additional 
diagnosis of 
schizotypal 
personality disorder, the personality disorder must 
have been present 
before the onset 
of psychotic symptoms and persist 
when the psychotic symptoms are in remission. When an 
individual 
has a persistent 
psychotic disorder (e.g., schizophrenia) that 
was preceded by 
schizotypal 
personality disorder, schizotypal 
personality disorder should also be recorded, 



followed by  premorbid  in parentheses. 
Neurodevelopmental 
disorders. 
There may be great 
difficulty differentiating children with 
schizotypal 
personality disorder from 
the heterogeneous group of solitary, odd children whose 
behavior is characterized by marked social 
isolation, eccentricity, or peculiarities of language 
and whose diagnoses would probably include milder forms of autism 
spectrum 
disorder or 
language communication disorders. Communication disorders may be differentiated by the 
primacy and severity of the disorder in language and by the characteristic features of impaired 
language found in a specialized language assessment. Milder forms of autism 
spectrum 
disorder 
are differentiated by the even greater lack of social 
awareness and emotional 
reciprocity and 


stereotyped behaviors and interests. 
Personality 
change 
due 
to 
another medical 
condition. 
Schizotypal 
personality disorder must 
be 
distinguished from 
personality change due to another medical 
condition, in which the traits that 


emerge are a direct physiological consequence of another medical condition. 
Substance 
use 
disorders. 
Schizotypal 
personality disorder must 
also be distinguished from 


symptoms that may develop in association with persistent substance use. 
Other personality 
disorders 
and 
personality 
traits. 
Other personality disorders may be confused with 
schizotypal 
personality disorder because they have certain features in common. It 
is, therefore, 


important 
to distinguish among these disorders based on differences in their characteristic 
features. However, if an individual 
has personality features that 
meet 
criteria for one or more 
personality disorders in addition to schizotypal 
personality disorder, all 
can be diagnosed. 
Although paranoid and schizoid personality disorders may also be characterized by social 
detachment and restricted affect, schizotypal personality disorder can be distinguished from these 
two diagnoses by the presence of cognitive or perceptual 
distortions and marked eccentricity or 
oddness. Close relationships are limited in both schizotypal 
personality disorder and avoidant 
personality disorder; 
however, in avoidant 
personality disorder an active desire for relationships 
is constrained by a fear of rejection, whereas in schizotypal 
personality disorder there is a lack of 
desire for relationships and persistent 
detachment. Individuals with narcissistic personality 
disorder may also display suspiciousness, social 
withdrawal, or alienation, but 
in narcissistic 
personality disorder these qualities derive primarily from 
fears of having imperfections or flaws 
revealed. Individuals with borderline personality disorder may also have transient, psychotic-like 
symptoms, but 
these are usually more closely related to affective shifts in response to stress (e.g., 
intense anger, anxiety, disappointment) and are usually more dissociative (e.g., derealization, 
depersonalization). In contrast, individuals with schizotypal 
personality disorder are more likely 
to have enduring psychotic-like symptoms that 
may worsen under stress but 
are less likely to be 
invariably associated with pronounced affective symptoms. Although social 
isolation may occur 
in borderline personality disorder, it 
is usually secondary to repeated interpersonal 
failures due to 
angry outbursts and frequent 
mood shifts, rather than a result 
of a persistent 
lack of social 
contacts and desire for intimacy. Furthermore, individuals with schizotypal 
personality disorder 
do not usually demonstrate the impulsive or manipulative behaviors of the individual with 


748 


borderline personality disorder. However, there is a high rate of co-occurrence between the two 
disorders, so that 
making such distinctions is not 
always feasible. Schizotypal 
features during 



adolescence may be reflective of transient 
emotional 
turmoil 
rather than an enduring personality 
disorder. 


Comorbidity 


Particularly in response to stress, individuals with this disorder may experience transient 
psychotic episodes (lasting minutes to hours), although they usually are insufficient 
in duration 
to warrant 
an additional 
diagnosis such as brief psychotic disorder or schizophreniform 
disorder. 
In some cases, clinically significant 
psychotic symptoms may develop that 
meet 
criteria for brief 
psychotic disorder, schizophreniform 
disorder, delusional 
disorder, or schizophrenia. There is 
considerable co-occurrence with schizoid, paranoid, avoidant, and borderline personality 
disorders. 


Cluster B Personality Disorders 


Antisocial 
Personality Disorder 


Diagnostic Criteria 
F60.2 


A. 
A 
pervasive 
pattern 
of 
disregard 
for and 
violation 
of 
the 
rights of 
others, 
occurring 
since 
age 
15 
years, 
as indicated 
by three 
(or more) of 
the 
following: 
1. 
Failure 
to 
conform to 
social norms with 
respect 
to 
lawful behaviors, 
as 
indicated 
by repeatedly performing 
acts that 
are 
grounds for arrest. 
2. 
Deceitfulness, 
as indicated 
by repeated 
lying, 
use 
of 
aliases, 
or conning 
others for personal profit 
or pleasure. 
3. 
Impulsivity or failure 
to 
plan 
ahead. 
4. 
Irritability and 
aggressiveness, 
as indicated 
by repeated 
physical fights or 
assaults. 
5. 
Reckless disregard 
for safety of 
self 
or others. 
6. 
Consistent 
irresponsibility, 
as indicated 
by repeated 
failure 
to 
sustain 
consistent 
work behavior or honor financial obligations. 
7. 
Lack of 
remorse, 
as indicated 
by being 
indifferent 
to 
or rationalizing 
having 
hurt, 
mistreated, 
or stolen 
from another. 
B. 
The 
individual is at 
least 
age 
18 
years. 
C. 
There 
is evidence 
of 
conduct 
disorder with 
onset 
before 
age 
15 
years. 
D. 
The 
occurrence 
of 
antisocial behavior is not 
exclusively during 
the 
course 
of 
schizophrenia 
or bipolar disorder. 
Diagnostic Features 



The essential 
feature of antisocial 
personality disorder is a pervasive pattern of disregard for, and 
violation of, the rights of others that 
begins in childhood or early adolescence and continues into 
adulthood. This pattern has also been referred to as psychopathy, 
sociopathy, 
or dyssocial 
personality disorder. 
Because deceit 
and manipulation are central 
features of antisocial 
personality disorder, it 
may be especially helpful 
to integrate information acquired from 
systematic clinical assessment with information collected from collateral sources. 


749 


For this diagnosis to be given, the individual 
must 
be at 
least 
age 18 years (Criterion B) and 
must 
have had evidence of conduct 
disorder with onset 
before age 15 years (Criterion C). 
Conduct 
disorder involves a repetitive and persistent 
pattern of behavior in which the basic rights 
of others or major age-appropriate societal 
norms or rules are violated. The specific behaviors 
characteristic of conduct 
disorder fall 
into one of four categories: 
aggression to people and 
animals, destruction of property, deceitfulness or theft, or serious violation of rules. 


The pattern of antisocial 
behavior continues into adulthood. Individuals with antisocial 
personality disorder fail 
to conform 
to social 
norms with respect 
to lawful 
behavior (Criterion 
A1). They may repeatedly perform 
acts that 
are grounds for arrest 
(whether they are arrested or 
not), such as destroying property, harassing others, stealing, or pursuing illegal 
occupations. 
Persons with this disorder disregard the wishes, rights, or feelings of others. They are frequently 
deceitful 
and manipulative in order to gain personal 
profit 
or pleasure (e.g., to obtain money, sex, 
or power) (Criterion A2). They may repeatedly lie, use an alias, con others, or malinger. A 
pattern of impulsivity may be manifested by a failure to plan ahead (Criterion A3). Decisions are 
made on the spur of the moment, without 
forethought 
and without 
consideration for the 
consequences to self or others; 
this may lead to sudden changes of jobs, residences, or 
relationships. Individuals with antisocial 
personality disorder tend to be irritable and aggressive 
and may repeatedly get 
into physical 
fights or commit 
acts of physical 
assault 
(including spouse 
beating or child beating) (Criterion A4). (Aggressive acts that 
are required to defend oneself or 
someone else are not 
considered to be evidence for this item.) These individuals also display a 
reckless disregard for the safety of themselves or others (Criterion A5). This may be evidenced 
in their driving behavior (i.e., recurrent 
speeding, driving while intoxicated, multiple accidents). 
They may engage in sexual 
behavior or substance use that 
has a high risk for harmful 
consequences. They may neglect or fail to care for a child in a way that puts the child in danger. 


Individuals with antisocial 
personality disorder also tend to be consistently and extremely 
irresponsible (Criterion A6). Irresponsible work behavior may be indicated by significant 
periods 
of unemployment 
despite available job opportunities, or by abandonment 
of several 
jobs without 
a realistic plan for getting another job. There may also be a pattern of repeated absences from 
work that 
are not 
explained by illness either in themselves or in their family. Financial 
irresponsibility is indicated by acts such as defaulting on debts, failing to provide child support, 
or failing to support 
other dependents on a regular basis. Individuals with antisocial 
personality 
disorder show little remorse for the consequences of their acts (Criterion A7). They may be 
indifferent 
to, or provide a superficial 
rationalization for, having hurt, mistreated, or stolen from 
someone (e.g.,  life s unfair,   losers deserve to lose ). These individuals may blame the victims 
for being foolish, helpless, or deserving their fate (e.g.,  he had it 
coming anyway ); 
they may 
minimize the harmful 
consequences of their actions; 
or they may simply indicate complete 



indifference. They generally fail 
to compensate or make amends for their behavior. They may 
believe that 
everyone is out 
to  help number one  and that 
one should stop at 
nothing to avoid 
being pushed around. 


The antisocial 
behavior must 
not 
occur exclusively during the course of schizophrenia or 
bipolar disorder (Criterion D). 


Associated Features 


Individuals with antisocial 
personality disorder frequently lack empathy and tend to be callous, 
cynical, and contemptuous of the feelings, rights, and sufferings of others. They may have an 
inflated and arrogant 
self-appraisal 
(e.g., feel 
that 
ordinary work is beneath them 
or lack a 
realistic concern about 
their current 
problems or their future) and may be excessively 
opinionated, self-assured, or cocky. Some antisocial 
individuals may display a glib, superficial 
charm 
and can be quite voluble and verbally facile (e.g., using technical 
terms or jargon that 
might impress someone who is unfamiliar with the topic). Lack of 


750 


empathy, inflated self-appraisal, and superficial 
charm 
are features that 
have been commonly 
included in traditional 
conceptions of psychopathy that 
may be particularly distinguishing of the 
disorder and more predictive of recidivism 
in prison or forensic settings, where criminal, 
delinquent, or aggressive acts are likely to be nonspecific. These individuals may also be 
irresponsible and exploitative in their sexual 
relationships. They may have a history of many 
sexual 
partners and may never have sustained a monogamous relationship. They may be 
irresponsible as parents, as evidenced by malnutrition of a child, an illness in the child resulting 
from 
a lack of minimal 
hygiene, a child s dependence on neighbors or nonresident 
relatives for 
food or shelter, a failure to arrange for a caretaker for a young child when the individual 
is away 
from 
home, or repeated squandering of money required for household necessities. These 
individuals may receive dishonorable discharges from 
the armed services, may fail 
to be self-
supporting, may become impoverished or even homeless, or may spend many years in penal 
institutions. Individuals with antisocial 
personality disorder are more likely than individuals in 
the general population to die prematurely from natural causes and suicide. 


Prevalence 


The estimated prevalence of antisocial 
personality disorder based on a probability subsample 
from 
Part 
II of 
the National 
Comorbidity Survey Replication was 0.6%.The prevalence of 
antisocial 
personality disorder in the National 
Epidemiologic Survey on Alcohol 
and Related 
Conditions data was 3.6%. A review of seven epidemiological 
studies (six in the United States) 
found a median prevalence of 3.6%. The highest 
prevalence of antisocial 
personality disorder 
(greater than 70%) is among samples of men with the most severe alcohol use disorders and from 
substance abuse clinics, prisons, or other forensic settings. Lifetime prevalence appears to be 
similar across non-Latinx White and Black individuals and lower in Latinx and Asian 
Americans. Prevalence may be higher in samples affected by adverse socioeconomic (i.e., 
poverty) or sociocultural (i.e., migration) factors. 



Development and Course 


Antisocial 
personality disorder has a chronic course but 
may become less evident 
or remit 
as the 
individual 
grows older, often by age 40. Although this remission tends to be particularly evident 
with respect 
to engaging in criminal 
behavior, there is likely to be a decrease in the full 
spectrum 
of antisocial 
behaviors and substance use. By definition, antisocial 
personality cannot 
be 
diagnosed before age 18 years. 


Risk and Prognostic Factors 


Environmental. 
Child abuse or neglect, unstable or erratic parenting, or inconsistent 
parental 
discipline may increase the likelihood that 
conduct 
disorder will 
evolve into antisocial 
personality disorder. 


Genetic 
and 
physiological. 
Antisocial 
personality disorder is more common among the first-degree 
biological 
relatives of those with the disorder than in the general 
population. Biological 
relatives 
of individuals with this disorder are also at 
increased risk for somatization disorder (a diagnosis 
that 
was replaced in DSM-5 with somatic symptom 
disorder) and substance use disorders. 
Within a family that 
has a member with antisocial 
personality disorder, males more often have 
antisocial 
personality disorder and substance use disorders, whereas females more often have 
somatization disorder. 


Culture-Related Diagnostic Issues 


Antisocial 
personality disorder has been associated with low socioeconomic status and urban 
settings. The diagnosis may at times be misapplied to individuals in settings in which 


751 


seemingly antisocial 
behavior may be part 
of a protective survival 
strategy (e.g., formation of 
youth gangs in urban areas with high rates of violence and discrimination). Sociocultural 
contexts with high rates of child maltreatment 
or exposure to violence also tend to have elevated 
prevalence of antisocial 
behaviors, suggesting either a potential 
risk factor for the development 
of antisocial 
personality disorder or an adverse environment 
that 
evokes reactive and contextual 
antisocial 
behaviors that 
do not 
represent 
pervasive and enduring traits consistent 
with a 
personality disorder. In assessing antisocial 
traits, it 
is helpful 
for the clinician to consider the 
social 
and economic context 
in which the behaviors occur. In the National 
Epidemiologic Survey 
on Alcohol 
and Related Conditions, prevalence appears to vary across U.S. ethnic and racialized 
groups, possibly because of a combination of true prevalence differences, measurement 
artifacts, 
and the impact 
of adverse environments that 
generate behaviors that 
resemble those of antisocial 
personality disorder but 
are instead reactive and contextual. Individuals from 
some socially 
oppressed groups may be at 
higher risk for misdiagnosis or overdiagnosis of antisocial 
personality disorder because they are more likely to be misdiagnosed with conduct 
disorder in 
adolescence, which is a requirement for a diagnosis of antisocial personality disorder. 


Sex- and Gender-Related Diagnostic Issues 


Antisocial 
personality disorder is three times as common in men than in women. Women with 



antisocial 
personality disorder are more likely to have experienced childhood and adult 
adverse 
experiences such as sexual 
abuse compared with men. Clinical 
presentation may vary, with men 
more often presenting with irritability/aggression and reckless disregard for the safety of others 
compared with women. Comorbid substance use disorders are more common in men, while 
comorbid mood and anxiety disorders are more common in women. There has been some 
concern that 
antisocial 
personality disorder may be underdiagnosed in females, particularly 
because of the emphasis on aggressive items in the definition of conduct disorder. 


Differential 
Diagnosis 


The diagnosis of antisocial 
personality disorder is not 
given to individuals younger than 18 years 
and is given only if there is evidence of conduct 
disorder before age 15 years. For individuals 
older than 18 years, a diagnosis of conduct 
disorder is given only if the criteria for antisocial 
personality disorder are not met. 


Substance 
use 
disorders. 


When antisocial 
behavior in an adult 
is associated with a substance use 
disorder, the diagnosis of antisocial 
personality disorder is not 
made unless the signs of antisocial 
personality disorder were also present 
in childhood and have continued into adulthood. When 
substance use and antisocial 
behavior both began in childhood and continued into adulthood, 
both a substance use disorder and antisocial 
personality disorder should be diagnosed if the 
criteria for both are met, even 
though some antisocial 
acts may be a consequence of the 
substance use disorder (e.g., illegal selling of drugs, thefts to obtain money for drugs). 


Schizophrenia 
and 
bipolar disorders. 
Antisocial 
behavior that 
occurs exclusively during the course 


of schizophrenia or a bipolar disorder should not be diagnosed as antisocial personality disorder. 
Other personality 
disorders. 
Other personality disorders may be confused with antisocial 
personality disorder because they have certain features in common. It 
is therefore important 
to 
distinguish among these disorders based on differences in their characteristic features. However, 
if an individual 
has personality features that 
meet 
criteria for one or more personality disorders in 
addition to antisocial 
personality disorder, all 
can be diagnosed. Individuals with antisocial 
personality disorder and narcissistic personality disorder share a tendency to be tough-minded, 
glib, superficial, exploitative, and lack empathy. However, 


752 


narcissistic personality disorder does not 
include characteristics of impulsivity, aggression, and 
deceit. In addition, individuals with antisocial 
personality disorder may not 
be as needy of the 
admiration and envy of others, and persons with narcissistic personality disorder usually lack the 
history of conduct 
disorder in childhood or criminal 
behavior in adulthood. Individuals with 
antisocial 
personality disorder and histrionic personality disorder share a tendency to be 
impulsive, superficial, excitement 
seeking, reckless, seductive, and manipulative, but 
persons 
with histrionic personality disorder tend to be more exaggerated in their emotions and do not 
characteristically engage in antisocial 
behaviors. Individuals with histrionic and borderline 
personality disorders are manipulative to gain nurturance, whereas those with antisocial 
personality disorder are manipulative to gain profit, power, or some other material 
gratification. 
Individuals with antisocial 
personality disorder tend to be less emotionally unstable and more 
aggressive than those with borderline personality disorder. Although antisocial 
behavior may be 



present 
in some individuals with paranoid personality disorder, it 
is not 
usually motivated by a 
desire for personal 
gain or to exploit 
others as in antisocial 
personality disorder, but 
rather is 
more often attributable to a desire for revenge. 
Criminal 
behavior not 
associated 
with 
a 
mental 
disorder. 
Antisocial 
personality disorder must 
be 


distinguished from 
antisocial 
behavior not 
due to a mental 
disorder, for example, criminal 
behavior undertaken for gain that 
is not 
accompanied by the personality features characteristic of 
this disorder. In these cases, the condition adult 
antisocial 
behavior may be coded (see  Other 
Conditions That May Be a Focus of Clinical Attention ). 


Comorbidity 


Individuals with antisocial 
personality disorder may also experience dysphoria, including 
complaints of tension, inability to tolerate boredom, and depressed mood. They may have 
associated anxiety disorders, mood disorders, substance use disorders, somatic symptom 
disorder, and gambling disorder. Individuals with antisocial 
personality disorder also often have 
personality features that 
meet 
criteria for other personality disorders, particularly borderline, 
histrionic, and narcissistic personality disorders. The likelihood of developing antisocial 
personality disorder in adult 
life is increased if the individual 
experienced childhood onset 
of 
conduct 
disorder (before age 10 years) and accompanying attention-deficit/hyperactivity 
disorder. 


Borderline Personality Disorder 


Diagnostic Criteria 
F60.3 


A 
pervasive 
pattern 
of 
instability of 
interpersonal relationships, 
self-image, 
and 
affects, 
and 
marked 
impulsivity, 
beginning 
by early adulthood 
and 
present 
in 
a 
variety of 
contexts, 
as indicated 
by five 
(or more) of 
the 
following: 


1. 
Frantic efforts to 
avoid 
real or imagined 
abandonment. 
(Note: 
Do 
not 
include 
suicidal or self-mutilating 
behavior covered 
in 
Criterion 
5.) 
2. 
A 
pattern 
of 
unstable 
and 
intense 
interpersonal relationships characterized 
by 
alternating 
between 
extremes of 
idealization 
and 
devaluation. 
3. 
Identity disturbance: 
markedly and 
persistently unstable 
self-image 
or sense 
of 
self. 
4. 
Impulsivity in 
at 
least 
two 
areas that 
are 
potentially self-damaging 
(e.g., 
spending, 
sex, 
substance 
abuse, 
reckless driving, 
binge 
eating). 
(Note: 
Do 
not 
include 
suicidal or self-mutilating 
behavior covered 
in 
Criterion 
5.) 
5. 
Recurrent 
suicidal behavior, 
gestures, 
or threats, 
or self-mutilating 
behavior. 
753 


6. 
Affective 
instability due 
to 
a 
marked 
reactivity of 
mood 
(e.g., 
intense 
episodic 
dysphoria, 
irritability, 
or anxiety usually lasting 
a 
few hours and 
only rarely more 

than 
a 
few days). 


7. 
Chronic feelings of 
emptiness. 
8. 
Inappropriate, 
intense 
anger or difficulty controlling 
anger (e.g., 
frequent 
displays 
of 
temper, 
constant 
anger, 
recurrent 
physical fights). 
9. 
Transient, 
stress-related 
paranoid 
ideation 
or severe 
dissociative 
symptoms. 
Diagnostic Features 


The essential 
feature of borderline personality disorder is a pervasive pattern of instability of 
interpersonal 
relationships, self-image, and affects, and marked impulsivity that 
begins by early 
adulthood and is present in a variety of contexts. 


Individuals with borderline personality disorder make frantic efforts to avoid real 
or 
imagined abandonment 
(Criterion 1). The perception of impending separation or rejection, or the 
loss of external 
structure, can lead to profound changes in self-image, affect, cognition, and 
behavior. These individuals are very sensitive to environmental 
circumstances. They experience 
intense abandonment 
fears and inappropriate anger even when faced with a realistic time-limited 
separation or when there are unavoidable changes in plans (e.g., sudden despair in reaction to a 
clinician s announcing the end of the hour; 
panic or fury when someone important 
to them 
is just 
a few minutes late or must 
cancel 
an appointment). They may believe that 
this  abandonment  
implies they are  bad.  These abandonment 
fears are related to an intolerance of being alone and 
a need to have other people with them. Their frantic efforts to avoid abandonment 
may include 
impulsive actions such as self-mutilating or suicidal 
behaviors, which are described separately in 
Criterion 5 (see also  Association With Suicidal Thoughts or Behavior ). 


Individuals with borderline personality disorder have a pattern of unstable and intense 
relationships (Criterion 2). They may idealize potential 
caregivers or lovers at 
the first 
or second 
meeting, demand to spend a lot 
of time together, and share the most 
intimate details early in a 
relationship. However, they may switch quickly from 
idealizing other people to devaluing them, 
feeling that 
the other person does not 
care enough, does not 
give enough, or is not 
 there  
enough. These individuals can empathize with and nurture other people, but 
only with the 
expectation that 
the other person will 
 be there  in return to meet 
their own needs on demand. 
These individuals are prone to sudden and dramatic shifts in their view of others, who may 
alternatively be seen as beneficent 
supports or as cruelly punitive. Such shifts often reflect 
disillusionment 
with a caregiver whose nurturing qualities had been idealized or whose rejection 
or abandonment is expected. 


There may be an identity disturbance characterized by markedly and persistently unstable 
self-image or sense of self (Criterion 3). There are sudden and dramatic shifts in self-image (e.g., 
suddenly changing from 
the role of a needy supplicant 
for help to that 
of a righteous avenger of 
past 
mistreatment). Although they usually have a self-image that 
is based on the feeling of being 
bad or evil, individuals with this disorder may at 
times have feelings that 
they do not 
exist 
at 
all. 
This can be both painful 
and frightening to those with this disorder. Such experiences usually 
occur in situations in which the individual 
feels a lack of a meaningful 
relationship, nurturing, 
and support. These individuals may show worse performance in unstructured work or school 
situations. This lack of a full 
and enduring identity makes it 
difficult 
for the individual 
with 
borderline personality disorder to identify maladaptive patterns of behavior and can lead to 
repetitive patterns of troubled relationships. 



Individuals with borderline personality disorder display impulsivity in at 
least 
two areas that 
are potentially self-damaging (Criterion 4). They may gamble, spend money irresponsibly, binge 
eat, abuse substances, engage in unsafe sex, or drive recklessly. 


754 


Individuals with this disorder display recurrent 
suicidal 
behavior, gestures, or threats, or self-
mutilating behavior (Criterion 5). Recurrent 
suicidal 
thoughts or behavior are often the reason 
that 
these individuals present 
for help. These self-destructive acts are usually precipitated by 
threats of separation or rejection or by expectations that 
the individual 
assume increased 
responsibility. Self-mutilative acts (e.g., cutting or burning) are very common and may occur 
during periods in which the individual 
is experiencing dissociative symptoms. These acts often 
bring relief by reaffirming the individual s ability to feel 
or by expiating the individual s sense of 
being evil. 


Individuals with borderline personality disorder may display affective instability that 
is due 
to a marked reactivity of mood (e.g., intense episodic dysphoria, irritability, or anxiety usually 
lasting a few hours and only rarely more than a few days) (Criterion 6). The basic dysphoric 
mood of those with borderline personality disorder is often disrupted by periods of anger, panic, 
or despair and is rarely relieved by periods of well-being or satisfaction. These episodes may 
reflect the individual s extreme reactivity to interpersonal stresses. 


Individuals with borderline personality disorder may be troubled by chronic feelings of 
emptiness, which can co-occur with painful 
feelings of aloneness (Criterion 7). Easily bored, 
they may frequently seek excitement to avoid their feelings of emptiness. 


Individuals with this disorder frequently express inappropriate, intense anger or have 
difficulty controlling their anger (Criterion 8). They may display extreme sarcasm, enduring 
bitterness, or verbal 
outbursts. The anger is often elicited when a caregiver or lover is seen as 
neglectful, withholding, uncaring, or abandoning. Such expressions of anger are often followed 
by shame and guilt and contribute to the feeling they have of being evil. 


During periods of extreme stress, transient 
paranoid ideation or dissociative symptoms (e.g., 
depersonalization) may occur (Criterion 9), but 
these are generally of insufficient 
severity or 
duration to warrant 
an additional 
diagnosis. These episodes occur most 
frequently in response to 
a real 
or imagined abandonment. Symptoms tend to be transient, lasting minutes or hours. The 
real or perceived return of the caregiver s nurturance may result in a remission of symptoms. 


Associated Features 


Individuals with borderline personality disorder may have a pattern of undermining themselves 
at 
the moment 
a goal 
is about 
to be realized (e.g., dropping out 
of school 
just 
before graduation; 
regressing severely after a discussion of how well 
therapy is going; 
destroying a good 
relationship just 
when it 
is clear that 
the relationship could last). Some individuals develop 
psychotic-like symptoms (e.g., hallucinations, body-image distortions, ideas of reference, 
hypnagogic phenomena) during times of stress. Individuals with this disorder may feel 
more 
secure with transitional 
objects (i.e., a pet 
or inanimate possession) than in interpersonal 
relationships. Premature death from 
suicide may occur in individuals with borderline personality 
disorder, especially in those with co-occurring depressive disorders or substance use disorders. 



However, deaths from 
other causes. such as accidents or illness, are more than twice as common 
as deaths by suicide in individuals with borderline personality disorder. Physical 
handicaps may 
result 
from 
self-inflicted abuse behaviors or failed suicide attempts. Recurrent 
job losses, 
interrupted education, and separation or divorce are common. Physical 
and sexual 
abuse, neglect, 
hostile conflict, and early parental 
loss are more common in the childhood histories of those with 
borderline personality disorder. 


Prevalence 


The estimated prevalence of borderline personality disorder based on a probability subsample 
from 
Part 
II of the National 
Comorbidity Survey Replication was 1.4%. The prevalence of 
borderline personality disorder in the National 
Epidemiologic Survey on Alcohol 
and Related 
Conditions data was 5.9%. A review of seven epidemiological studies (six in 


755 


the United States) found a median prevalence of 2.7%. The prevalence of borderline personality 
disorder is about 
6% in primary care settings, about 
10% among individuals seen in outpatient 
mental health clinics, and about 20% among psychiatric inpatients. 


Development and Course 


Borderline personality disorder has typically been thought 
of as an adult-onset 
disorder. 
However, it 
has been found in treatment 
settings that 
symptoms in adolescents as young as age 
12 or 13 years can meet 
full 
criteria for the disorder. It 
is not 
yet 
known what 
percentage of 
adults first 
entering treatment 
actually have such an early onset 
of borderline personality 
disorder. 


Borderline personality disorder has long been thought 
of as a disorder with a poor 
symptomatic course, which tended to lessen in severity as those with borderline personality 
disorder entered their 30s and 40s. However, prospective follow-up studies have found that 
stable remissions of 1 8 years are very common. Impulsive symptoms of borderline personality 
disorder remit 
the most 
rapidly, while affective symptoms remit 
at 
a substantially slower rate. In 
contrast, recovery from 
borderline personality disorder (i.e., concurrent 
symptomatic remission 
and good psychosocial functioning) is more difficult to achieve and less stable over time. Lack of 
recovery is associated with supporting oneself on disability benefits and suffering from 
poor 
physical health. 


Risk and Prognostic Factors 


Environmental. 
Borderline personality disorder has also been found to be associated with high 
rates of various forms of reported childhood abuse and emotional 
neglect. However, reported 
rates of sexual 
abuse are higher in inpatients than in outpatients with this disorder, suggesting 
that 
a history of sexual 
abuse is as much a risk factor for severity of borderline psychopathology 
as it 
is for the disorder itself. In addition, an empirically based consensus has arisen that 
suggests 
that 
a childhood history of reported sexual 
abuse is neither necessary nor sufficient 
for the 
development of borderline personality disorder. 


Genetic 
and 
physiological. 
Borderline personality disorder is about 
five times more common 



among first-degree biological 
relatives of those with the disorder than in the general 
population. 
There is also an increased familial 
risk for substance use disorders, anxiety disorders, antisocial 
personality disorder, and depressive or bipolar disorders. 


Culture-Related Diagnostic Issues 


The pattern of behavior seen in borderline personality disorder has been identified in many 
settings around the world. Sociocultural 
contexts characterized by social 
demands that 
evoke 
attempts at 
self-affirmation and acceptance by others, ambiguous or conflictual 
relationships 
with authority figures, or marked uncertainties in adaptation can foster impulsivity, emotional 
instability, explosive or aggressive behaviors, and dissociative experiences that 
are associated 
with borderline personality disorder or with transient 
and contextual 
reactions to those 
environments that 
can be confused with borderline personality disorder. Given that 
psychodynamic, cognitive, behavioral, and mindfulness aspects of models of mind and self vary 
cross-culturally, symptoms or traits that 
suggest 
the presence of borderline personality disorder 
(e.g., number of sexual 
partners, shifting between relationships, substance use) must 
be evaluated 
in light of cultural norms to make a valid diagnosis. 


Sex- and Gender-Related Diagnostic Issues 


While borderline personality disorder is more common among women than men in clinical 
samples, community samples demonstrate no difference in prevalence between men and women. 
This discrepancy may reflect a higher degree of help-seeking among women, 


756 


leading them 
to clinical 
settings. Clinical 
characteristics of men and women with borderline 
personality disorder appear to be similar, with potentially a higher degree of externalizing 
behaviors in boys and men and internalizing behaviors in girls and women. 


Association With Suicidal 
Thoughts or Behavior 


ln a longitudinal 
study, impulsive and antisocial 
behaviors of individuals with borderline 
personality disorder were associated with increased suicide risk. In a sample of hospitalized 
patients with borderline personality disorder followed prospectively for 24 years, around 6% 
died by suicide, compared with 1.4% in a comparison sample of individuals with personality 
disorders other than borderline personality disorder. A study of individuals with borderline 
personality disorder followed for 10 years found that 
recurrent 
suicidal 
behavior was a defining 
characteristic of borderline personality disorder, associated with declining rates of suicide 
attempts from 79% to 13% over time. 


Differential 
Diagnosis 


Depressive 
and 
bipolar disorders. 
Borderline personality disorder often co-occurs with depressive 
or bipolar disorders, and when criteria for both are met, both should be diagnosed. Because the 
cross-sectional 
presentation of borderline personality disorder can be mimicked by an episode of 
depressive or bipolar disorder, the clinician should avoid giving an additional 
diagnosis of 



borderline personality disorder based only on cross-sectional 
presentation without 
having 


documented that the pattern of behavior had an early onset and a long-standing course. 
Separation 
anxiety 
disorder in 
adults. 
Separation anxiety disorder and borderline personality 
disorder are characterized by fear of abandonment 
by loved ones, but 
problems in identity, self-
direction, interpersonal 
functioning, and impulsivity are additionally central 
to borderline 
personality disorder. 


Other personality 
disorders. 
Other personality disorders may be confused with borderline 
personality disorder because they have certain features in common. It 
is therefore important 
to 
distinguish among these disorders based on differences in their characteristic features. However, 
if an individual 
has personality features that 
meet 
criteria for one or more personality disorders in 
addition to borderline personality disorder, all 
can be diagnosed. Although histrionic personality 
disorder can also be characterized by attention seeking, manipulative behavior, and rapidly 
shifting emotions, borderline personality disorder is distinguished by self-destructiveness, angry 
disruptions in close relationships, and chronic feelings of deep emptiness and loneliness. 
Paranoid ideas or illusions may be present 
in both borderline personality disorder and 
schizotypal 
personality disorder, but 
these symptoms are more transient, interpersonally reactive, 
and responsive to external 
structuring in borderline personality disorder. Although paranoid 
personality disorder and narcissistic personality disorder may also be characterized by an angry 
reaction to minor stimuli, the relative stability of self-image, as well 
as the relative lack of 
physical 
self-destructiveness, repetitive impulsivity, and profound abandonment 
concerns, 
distinguishes these disorders from 
borderline personality disorder. Although antisocial 
personality disorder and borderline personality disorder are both characterized by manipulative 
behavior, individuals with antisocial 
personality disorder are manipulative to gain profit, power, 
or some other material 
gratification, whereas the goal 
in borderline personality disorder is 
directed more toward gaining the concern of caretakers. Both dependent 
personality disorder and 
borderline personality disorder are characterized by fear of abandonment; 
however, the 
individual 
with borderline personality disorder reacts to abandonment 
with feelings of emotional 
emptiness, rage, and demands, whereas the individual 
with dependent 
personality disorder reacts 
with increasing appeasement 
and submissiveness and urgently seeks a replacement 
relationship 
to provide caregiving and support. Borderline personality disorder can 


757 


further be distinguished from 
dependent 
personality disorder by the typical 
pattern of unstable 
and intense relationships. 
Personality 
change 
due 
to 
another medical 
condition. 
Borderline personality disorder must 
be 


distinguished from 
personality change due to another medical 
condition, in which the traits that 


emerge are a direct physiological consequence of another medical condition. 
Substance 
use 
disorders. 
Borderline personality disorder must 
also be distinguished from 
symptoms that may develop in association with persistent substance use. 


Identity 
problems. 
Borderline personality disorder should be distinguished from 
an identity 
problem, which is reserved for identity concerns related to a developmental 
phase (e.g., 
adolescence) and does not 
qualify as a mental 
disorder. Adolescents and young adults with 
identity problems (especially when accompanied by substance use) may transiently display 



behaviors that 
misleadingly give the impression of borderline personality disorder. Such 
situations are characterized by emotional 
instability, existential 
dilemmas, uncertainty, anxiety-
provoking choices, conflicts about 
sexual 
orientation, and competing social 
pressures to decide 
on careers. 


Comorbidity 


Common co-occurring disorders include depressive and bipolar disorders, substance use 
disorders, anxiety disorders (particularly panic disorder and social 
anxiety disorder), eating 
disorders (notably bulimia nervosa and binge-eating disorder), posttraumatic stress disorder, and 
attention-deficit/hyperactivity disorder. Borderline personality disorder also frequently co-occurs 
with the other personality disorders. 


Histrionic Personality Disorder 


Diagnostic Criteria 
F60.4 


A 
pervasive 
pattern 
of 
excessive 
emotionality and 
attention 
seeking, 
beginning 
by 
early adulthood 
and 
present 
in 
a 
variety of 
contexts, 
as indicated 
by five 
(or more) of 
the 
following: 


1. 
Is uncomfortable 
in 
situations in 
which 
he 
or she 
is not 
the 
center of 
attention. 
2. 
Interaction 
with 
others is often 
characterized 
by inappropriate 
sexually seductive 
or provocative 
behavior. 
3. 
Displays rapidly shifting 
and 
shallow expression 
of 
emotions. 
4. 
Consistently uses physical appearance 
to 
draw attention 
to 
self. 
5. 
Has a 
style 
of 
speech 
that 
is excessively impressionistic and 
lacking 
in 
detail. 
6. 
Shows self-dramatization, 
theatricality, 
and 
exaggerated 
expression 
of 
emotion. 
7. 
Is suggestible 
(i.e., 
easily influenced 
by others or circumstances). 
8. 
Considers relationships to 
be 
more 
intimate 
than 
they actually are. 
Diagnostic Features 


The essential 
feature of histrionic personality disorder is pervasive and excessive emotionality 
and attention-seeking behavior. This pattern begins by early adulthood and is present 
in a variety 
of contexts. 


Individuals with histrionic personality disorder are uncomfortable or feel 
unappreciated when 
they are not 
the center of attention (Criterion 1). Often lively and dramatic, they tend to draw 
attention to themselves and may initially charm 
new acquaintances by their enthusiasm, apparent 
openness, or flirtatiousness. These qualities wear thin, however, as these individuals continually 
demand to be the center of attention. They commandeer the 


758 


role of  the life of the party.  If they are not 
the center of attention, they may do something 



dramatic (e.g., make up stories, create a scene) to draw the focus of attention to themselves. This 
need is often apparent 
in their behavior with a clinician (e.g., being flattering, bringing gifts, 
providing dramatic descriptions of physical 
and psychological 
symptoms that 
are replaced by 
new symptoms each visit). 


The appearance and behavior of individuals with this disorder are often inappropriately 
sexually provocative or seductive (Criterion 2). This behavior not only is directed toward persons 
in whom 
the individual 
has a sexual 
or romantic interest 
but 
also occurs in a wide variety of 
social, occupational, and professional 
relationships beyond what 
is appropriate for the social 
context. Emotional 
expression may be shallow and rapidly shifting (Criterion 3). Individuals 
with this disorder consistently use physical 
appearance to draw attention to themselves (Criterion 
4). They are overly concerned with impressing others by their appearance and expend an 
excessive amount 
of time, energy, and money on clothes and grooming. They may  fish for 
compliments  regarding appearance and may be easily and excessively upset 
by a critical 
comment about how they look or by a photograph that they regard as unflattering. 


These individuals have a style of speech that 
is excessively impressionistic and lacking in 
detail 
(Criterion 5). Strong opinions are expressed with dramatic flair, but 
underlying rationales 
are usually vague and diffuse, without 
supporting facts and details. For example, an individual 
with histrionic personality disorder may comment 
that 
a certain individual 
is a wonderful 
human 
being, yet 
be unable to provide any specific examples of good qualities to support 
this opinion. 
Individuals with this disorder are characterized by self-dramatization, theatricality, and an 
exaggerated expression of emotion (Criterion 6). They may embarrass friends and acquaintances 
by an excessive public display of emotions (e.g., embracing casual 
acquaintances with excessive 
ardor, sobbing uncontrollably on minor sentimental 
occasions, having temper tantrums). 
However, their emotions often seem 
to be turned on and off too quickly to be deeply felt, which 
may lead others to accuse the individual of faking these feelings. 


Individuals with histrionic personality disorder have a high degree of suggestibility (Criterion 
7). Their opinions and feelings are easily influenced by others and by current 
fads. They may be 
overly trusting, especially of strong authority figures whom 
they see as magically solving their 
problems. They have a tendency to play hunches and to adopt 
convictions quickly. Individuals 
with this disorder often consider relationships more intimate than they actually are, describing 
almost 
every acquaintance as  my dear, dear friend  or referring to physicians met 
only once or 
twice under professional circumstances by their first names (Criterion 8). 


Associated Features 


Impairment 
in general 
tends to be lower in histrionic personality disorder than in many other 
personality disorders. However, the impairment 
most 
associated with histrionic personality 
disorder appears to be interpersonal 
in nature. Individuals with histrionic personality disorder 
have an interpersonal 
style characterized by social 
dominance, which can span a spectrum 
of 
behaviors that 
include a  warmer dominance  that 
can be intrusive in nature (e.g., need to be 
center of attention; 
exhibitionistic) to a  colder dominance  that 
can include arrogant, 
controlling, and aggressive behaviors. Romantic relationships appear to be particularly impaired, 
with evidence suggesting that 
individuals with histrionic personality disorder symptoms are more 
likely to get 
divorced or never get 
married. Individuals with histrionic personality disorder may 
have difficulty achieving emotional 
intimacy in romantic or sexual 
relationships. Individuals 



with this disorder often have impaired relationships with same-sex friends because their sexually 
provocative interpersonal 
style may seem 
a threat 
to their friends  relationships. These 
individuals may also alienate friends with demands for constant 
attention. They often become 
depressed and 


759 


upset 
when they are not 
the center of attention. They may crave novelty, stimulation, and 
excitement 
and have a tendency to become bored with their usual 
routine. These individuals are 
often intolerant 
of, or frustrated by, situations that 
involve delayed gratification, and their actions 
are often directed at 
obtaining immediate satisfaction. Although they often initiate a job or 
project 
with great 
enthusiasm, their interest 
may lag quickly. Longer-term 
relationships may be 
neglected to make way for the excitement of new relationships. 


Prevalence 


The estimated prevalence of histrionic personality disorder based on a probability subsample 
from 
Part 
II of 
the National 
Comorbidity Survey Replication was 0.0%.The prevalence of 
histrionic personality disorder in the National 
Epidemiologic Survey on Alcohol 
and Related 
Conditions data was 1.8%. A review of five epidemiological 
studies (four in the United States) 
found a median prevalence of 0.9%. 


Culture-Related Diagnostic Issues 


Norms for interpersonal 
behavior, personal 
appearance, and emotional 
expressiveness vary 
widely across cultures, genders, and age groups. Before considering the various traits (e.g., 
emotionality, seductiveness, dramatic interpersonal 
style, novelty seeking, sociability, charm, 
impressionability, a tendency to somatization) to be evidence of histrionic personality disorder, it 
is important 
to evaluate whether they cause clinically significant 
impairment 
or distress. The 
presence of histrionic personality disorder should be distinguished from 
reactive and contextual 
expression of these traits, arising in response to socialization pressures in competitive peer 
groups, including the  need to be liked,  that 
do not 
represent 
pervasive and enduring traits 
consistent with a personality disorder. 


Sex- and Gender-Related Diagnostic Issues 


In clinical 
settings, this disorder has been diagnosed more frequently in females; 
however, the 
gender ratio is not 
significantly different 
from 
the gender ratio of females within the respective 
clinical 
setting. In contrast, some studies using structured assessments report 
similar prevalence 
rates among males and females. 


Association With Suicidal 
Thoughts or Behavior 


The actual 
risk of suicide is not 
known, but 
clinical 
experience suggests that 
individuals with this 
disorder may be at increased risk for suicidal gestures and threats. 


Differential 
Diagnosis 



Other personality 
disorders 
and 
personality 
traits. 
Other personality disorders may be confused with 
histrionic personality disorder because they have certain features in common. It 
is therefore 
important 
to distinguish among these disorders based on differences in their characteristic 
features. However, if an individual 
has personality features that 
meet 
criteria for one or more 
personality disorders in addition to histrionic personality disorder, all 
can be diagnosed. 
Although borderline personality disorder can also be characterized by attention seeking, 
manipulative behavior, and rapidly shifting emotions, it 
is distinguished by self-destructiveness, 
angry disruptions in close relationships, and chronic feelings of deep emptiness and identity 
disturbance. Individuals with antisocial 
personality disorder and histrionic personality disorder 
share a tendency to be impulsive, superficial, excitement 
seeking, reckless, seductive, and 
manipulative, but 
persons with histrionic personality disorder tend to be more exaggerated in 
their emotions and do not 
characteristically engage in antisocial 
behaviors. Individuals with 
histrionic personality disorder are manipulative to gain nurturance, whereas those with antisocial 
personality disorder are manipu 


760 


lative to gain profit, power, or some other material 
gratification. Although individuals with 
narcissistic personality disorder also crave attention from 
others, they usually want 
praise for 
their  superiority,  whereas individuals with histrionic personality disorder are willing to be 
viewed as fragile or dependent 
if this is instrumental 
in getting attention. Individuals with 
narcissistic personality disorder may exaggerate the intimacy of their relationships with other 
people, but 
they are more apt 
to emphasize the  VIP  status or wealth of their friends. In 
dependent 
personality disorder, the individual 
is excessively dependent 
on others for praise and 
guidance, but 
is without 
the flamboyant, exaggerated, emotional 
features of individuals with 
histrionic personality disorder. 


Many individuals may display histrionic personality traits. Only when these traits are 
inflexible, maladaptive, and persisting and cause significant 
functional 
impairment 
or subjective 
distress do they constitute histrionic personality disorder. 
Personality 
change 
due 
to 
another medical 
condition. 
Histrionic personality disorder must 
be 


distinguished from 
personality change due to another medical 
condition, in which the traits that 


emerge are a direct physiological consequence of another medical condition. 
Substance 
use 
disorders. 
The disorder must 
also be distinguished from 
symptoms that 
may 
develop in association with persistent substance use. 


Comorbidity 


Histrionic personality disorder has been associated with higher rates of borderline, narcissistic, 
paranoid, dependent, and antisocial 
personality disorders; 
alcohol 
and other substance use and 
misuse; 
as well 
as aggression and violence. Histrionic personality disorder is also thought 
to be 
related to somatic symptom 
disorder, functional 
neurological 
symptom 
disorder (conversion 
disorder), and major depressive disorder. 


Narcissistic Personality Disorder 



Diagnostic Criteria 
F60.81 


A 
pervasive 
pattern 
of 
grandiosity (in 
fantasy or behavior), 
need 
for admiration, 
and 
lack of 
empathy, 
beginning 
by early adulthood 
and 
present 
in 
a 
variety of 
contexts, 
as indicated 
by five 
(or more) of 
the 
following: 


1. 
Has a 
grandiose 
sense 
of 
self-importance 
(e.g., 
exaggerates achievements and 
talents, 
expects to 
be 
recognized 
as superior without 
commensurate 
achievements). 
2. 
Is preoccupied 
with 
fantasies of 
unlimited 
success, 
power, 
brilliance, 
beauty, 
or 
ideal love. 
3. 
Believes that 
he 
or she 
is  special  and 
unique 
and 
can 
only be 
understood 
by, 
or 
should 
associate 
with, 
other special or high-status people 
(or institutions). 
4. 
Requires excessive 
admiration. 
5. 
Has a 
sense 
of 
entitlement 
(i.e., 
unreasonable 
expectations of 
especially 
favorable 
treatment 
or automatic compliance 
with 
his or her expectations). 
6. 
Is interpersonally exploitative 
(i.e., 
takes advantage 
of 
others to 
achieve 
his or 
her own 
ends). 
7. 
Lacks empathy: 
is unwilling 
to 
recognize 
or identify with 
the 
feelings and 
needs 
of 
others. 
8. 
Is often 
envious of 
others or believes that 
others are 
envious of 
him or her. 
9. 
Shows arrogant, 
haughty behaviors or attitudes. 
761 


Diagnostic Features 


The essential 
feature of narcissistic personality disorder is a pervasive pattern of grandiosity, 
need for admiration, and lack of empathy that 
begins by early adulthood and is present 
in a 
variety of contexts. 


Individuals with this disorder have a grandiose sense of self-importance, which may be 
manifest 
as an exaggerated or unrealistic sense of superiority, value, or capability (Criterion 1). 
They tend to overestimate their abilities and amplify their accomplishments, often appearing 
boastful 
and pretentious. They may blithely assume that 
others attribute the same value to their 
efforts and may be surprised when the praise they expect 
and feel 
they deserve is not 
forthcoming. Often implicit 
in the inflated judgments of their own accomplishments is an 
underestimation or devaluation of the contributions of others. Individuals with narcissistic 
personality disorder are often preoccupied with fantasies of unlimited success, power, brilliance, 
beauty, or ideal 
love (Criterion 2). They may ruminate about 
 long overdue  admiration and 
privilege and compare themselves favorably with famous or privileged people. 


Individuals with narcissistic personality disorder believe that 
they are special 
or unique and 
expect 
others to recognize them 
as such (Criterion 3). They can be surprised or even devastated 
when the recognition of acclaim 
they expect 
and feel 
they deserve from 
others is not 
forthcoming. They may feel 
that 
they can only be understood by, and should only associate with, 
people of high status and may attribute  unique,   perfect,  or  gifted  qualities to those with 



whom 
they associate. Individuals with this disorder believe that 
their needs are special 
and 
beyond the ken of ordinary people. Their own self-esteem 
is enhanced (i.e.,  mirrored ) by the 
idealized value that 
they assign to those with whom 
they associate. They are likely to insist 
on 
having only the  top  person (doctor, lawyer, hairdresser, instructor) or being affiliated with the 
 best  institutions but may devalue the credentials of those who disappoint them. 


Individuals with this disorder generally require excessive admiration (Criterion 4). Their self-
esteem 
is almost 
invariably very fragile, and their struggle with severe internal 
self-doubt, self-
criticism, and emptiness results in their need to actively seek others  admiration. They may be 
preoccupied with how well 
they are doing and how favorably they are regarded by others. They 
may expect 
their arrival 
to be greeted with great 
fanfare and are astonished if others do not 
covet 
their possessions. They may constantly fish for compliments, often with great charm. 


A sense of entitlement, which is rooted in their distorted sense of self-worth, is evident 
in 
these individuals  unreasonable expectation of especially favorable treatment 
(Criterion 5). They 
expect 
to be catered to and are puzzled or furious when this does not 
happen. For example, they 
may assume that 
they do not 
have to wait 
in line and that 
their priorities are so important 
that 
others should defer to them, and then get 
irritated when others fail 
to assist 
 in their very 
important 
work.  They expect 
to be given whatever they want 
or feel 
they need, no matter what 
it 
might 
mean to others. For example, these individuals may expect 
great 
dedication from 
others 
and may overwork them 
without 
regard for the impact 
on their lives. This sense of entitlement, 
combined with a lack of understanding and sensitivity to the wants and needs of others, may 
result 
in the conscious or unwitting exploitation of others (Criterion 6). They tend to form 
friendships or romantic relationships only if the other person seems likely to advance their 
purposes or otherwise enhance their self-esteem. They often usurp special 
privileges and extra 
resources that 
they believe they deserve. Some individuals with narcissistic personality disorder 
intentionally and purposefully take advantage of others emotionally, socially, intellectually, or 
financially for their own purposes and gains. 


Individuals with narcissistic personality disorder generally have a lack of empathy and are 
unwilling to recognize or identify with the desires, subjective experiences, and feelings of others 
(Criterion 7). They tend to have some degree of cognitive empathy 


762 


(understanding another person s perspective on an intellectual 
level) but 
lack emotional 
empathy (directly feeling the emotions that 
another person is feeling). These individuals may be 
oblivious to the hurt 
their remarks may inflict 
(e.g., exuberantly telling a former lover that 
 I am 
now in the relationship of a lifetime! ; 
boasting of health in front 
of someone who is sick). When 
recognized, the needs, desires, or feelings of others are likely to be viewed disparagingly as signs 
of weakness or vulnerability. Those who relate to individuals with narcissistic personality 
disorder typically find an emotional coldness and lack of reciprocal interest. 


These individuals are often envious of others or believe that 
others are envious of them 
(Criterion 8). They may begrudge others their successes or possessions, feeling that 
they better 
deserve those achievements, admiration, or privileges. They may harshly devalue the 
contributions of others, particularly when those individuals have received acknowledgment 
or 
praise for their accomplishments. Arrogant, haughty behaviors characterize these individuals; 
they often display snobbish, disdainful, or patronizing attitudes (Criterion 9). 



Associated Features 


Vulnerability in self-esteem 
makes individuals with narcissistic personality disorder very 
sensitive to criticism 
or defeat. Although they may not 
show it 
outwardly, such experiences may 
leave them 
feeling ashamed, humiliated, degraded, hollow, and empty. They may react 
with 
disdain, rage, or defiant 
counterattack. However, such experiences can also lead to social 
withdrawal 
or an appearance of humility that 
may mask and protect 
the grandiosity. 
Interpersonal 
relations are typically impaired because of problems related to self-preoccupation, 
entitlement, need for admiration, and relative disregard for the sensitivities of others. 


Individuals with narcissistic personality disorder can be competent 
and high functioning with 
professional 
and social 
success, while others can have various levels of functional 
impairment. 
Professional 
capability combined with self-control, stoicism, and interpersonal 
distancing with 
minimal 
self-disclosure can support 
sustained life engagement 
and even enable marriage and 
social 
affiliations. Sometimes ambition and temporary confidence lead to high achievements, but 
performance can be disrupted because of fluctuating self-confidence and intolerance of criticism 
or defeat. Some individuals with narcissistic personality disorder have very low vocational 
functioning, reflecting an unwillingness to take a risk in competitive or other situations in which 
failure or defeat can be possible. 


Low self-esteem 
with inferiority, vulnerability, and sustained feelings of shame, envy, and 
humiliation accompanied by self-criticism 
and insecurity can make individuals with narcissistic 
personality disorder susceptible to social 
withdrawal, emptiness, and depressed mood. High 
perfectionist 
standards are often associated with significant 
fear of exposure to imperfection, 
failure, and overwhelming emotions. 


Prevalence 


The estimated prevalence of narcissistic personality disorder based on a probability subsample 
from 
Part 
II of 
the National 
Comorbidity Survey Replication was 0.0%.The prevalence of 
narcissistic personality disorder in the National 
Epidemiologic Survey on Alcohol 
and Related 
Conditions data was 6.2%. A review of five epidemiological 
studies (four in the United States) 
found a median prevalence of 1.6%. 


Development and Course 


Narcissistic traits may be particularly common in adolescents but 
do not 
necessarily indicate that 
the individual 
will 
develop narcissistic personality disorder in adulthood. Predominant 
narcissistic traits or manifestations of the full 
disorder may first 
come to clinical 
attention or be 
exacerbated in the context of unexpected or extremely challenging life 


763 


experiences or crises, such as bankruptcies, demotions or loss of work, or divorces. In addition, 
individuals with narcissistic personality disorder may have specific difficulties adjusting to the 
onset 
of physical 
and occupational 
limitations that 
are inherent 
in the aging process. However, 
life experiences, such as new durable relationships, real 
successful 
achievements, and tolerable 
disappointments and setbacks, can all 
be corrective and contribute to changes and improvements 
in individuals with this disorder. 



Culture-Related Diagnostic Issues 


Narcissistic traits may be elevated in sociocultural 
contexts that 
emphasize individualism 
and 
personal 
autonomy over collectivistic goals. Compared with collectivistic contexts, in 
individualistic contexts, narcissistic traits may warrant 
less clinical 
attention or less frequently 
lead to social impairment. 


Sex- and Gender-Related Diagnostic Issues 


Among adults age 18 and older diagnosed with narcissistic personality disorder, 50% 75% are 
men. Gender differences in adults with this disorder include stronger reactivity in response to 
stress and compromised empathic processing in men as opposed to self-focus and withdrawal 
in 
women. Culturally based gender patterns and expectations may also contribute to gender 
differences in narcissistic personality disorder traits and patterns. 


Association With Suicidal 
Thoughts or Behavior 


In the context 
of severe stress, and given the perfectionism 
often associated with narcissistic 
personality disorder, exposure to imperfection, failure, and overwhelming emotions can evoke 
suicidal 
ideation. Suicide attempts in individuals with narcissistic personality disorder tend to be 
less impulsive and are characterized by higher lethality compared with suicide attempts by 
individuals with other personality disorders. 


Differential 
Diagnosis 


Other personality 
disorders 
and 
personality 
traits. 
Other personality disorders may be confused with 
narcissistic personality disorder because they have certain features in common. It 
is, therefore, 
important 
to distinguish among these disorders based on differences in their characteristic 
features. However, if an individual 
has personality features that 
meet 
criteria for one or more 
personality disorders in addition to narcissistic personality disorder, all 
can be diagnosed. The 
most 
useful 
feature in discriminating narcissistic personality disorder from 
histrionic, antisocial, 
and borderline personality disorders, in which the interactive styles are coquettish, callous, and 
needy, respectively, is the grandiosity characteristic of narcissistic personality disorder. The 
relative stability of self-image and self-control 
as well 
as the relative lack of self-destructiveness, 
impulsivity, separation insecurity, and emotional 
hyperreactivity also help distinguish 
narcissistic personality disorder from borderline personality disorder. 


Excessive pride in achievements, a relative lack of emotional 
display, and ignorance of or 
disdain for others  sensitivities help distinguish narcissistic personality disorder from 
histrionic 
personality disorder. Although individuals with borderline, histrionic, and narcissistic personality 
disorders may require much attention, those with narcissistic personality disorder specifically 
need that 
attention to be admiring. Individuals with antisocial 
and narcissistic personality 
disorders share a tendency to be tough-minded, glib, superficial, exploitative, and unempathic. 
However, narcissistic personality disorder does not 
necessarily include characteristics of 
impulsive aggressivity and deceitfulness. In addition, individuals with antisocial 
personality 
disorder may be more indifferent 
and less sensitive to others  reactions or criticism, and 
individuals with narcissistic personality disorder usually lack the history of conduct 
disorder in 
childhood or criminal behavior in adulthood. 



764 


In both narcissistic personality disorder and obsessive-compulsive personality disorder, the 
individual 
may profess a commitment 
to perfectionism 
and believe that 
others cannot 
do things 
as well. However, while those with obsessive-compulsive personality disorder tend to be more 
immersed in perfectionism 
related to order and rigidity, individuals with narcissistic personality 
disorder tend to set 
high perfectionistic standards, especially for appearance and performance, 
and to be critically concerned if they are not measuring up. 


Suspiciousness and social 
withdrawal 
usually distinguish those with schizotypal, avoidant, or 
paranoid personality disorder from 
those with narcissistic personality disorder. When these 
qualities are present 
in individuals with narcissistic personality disorder, they derive primarily 
from shame and fear of failure, or fear of having imperfections or flaws revealed. 


Many highly successful 
individuals display personality traits that 
might 
be considered 
narcissistic. Only when these traits are inflexible, maladaptive, and persisting and cause 
significant 
functional 
impairment 
or subjective distress do they constitute narcissistic personality 
disorder. 


Mania 
or hypomania. 
Grandiosity may emerge as part 
of manic or hypomanic episodes, but 
the 
association with mood change or functional 
impairments helps distinguish these episodes from 
narcissistic personality disorder. 


Substance 
use 
disorders. 
Narcissistic personality disorder must 
also be distinguished from 


symptoms that may develop in association with persistent substance use. 
Persistent 
depressive 
disorder. 
Experiences that 
threaten self-esteem 
can evoke a deep sense of 
inferiority and sustained feelings of shame, envy, self-criticism, and insecurity in individuals 
with narcissistic personality disorder that 
can result 
in persistent 
negative feelings resembling 
those seen in persistent 
depressive disorder. If criteria are also met 
for persistent 
depressive 
disorder, both conditions can be diagnosed. 


Comorbidity 


Narcissistic personality disorder is associated with depressive disorders (persistent 
depressive 
disorder and major depressive disorder), anorexia nervosa, and substance use disorders 
(especially related to cocaine). Histrionic, borderline, antisocial, and paranoid personality 
disorders may also be associated with narcissistic personality disorder. 


Cluster C Personality Disorders 


Avoidant Personality Disorder 


F60.6Diagnostic Criteria
A 
pervasive 
pattern 
of 
social inhibition, 
feelings of 
inadequacy, 
and 
hypersensitivity 



to 
negative 
evaluation, 
beginning 
by early adulthood 
and 
present 
in 
a 
variety of 
contexts, 
as indicated 
by four (or more) of 
the 
following: 


1. 
Avoids occupational activities that 
involve 
significant 
interpersonal contact 
because 
of 
fears of 
criticism, 
disapproval, 
or rejection. 
2. 
Is unwilling 
to 
get 
involved 
with 
people 
unless certain 
of 
being 
liked. 
765 


3. 
Shows restraint 
within 
intimate 
relationships because 
of 
the 
fear of 
being 
shamed 
or ridiculed. 
4. 
Is preoccupied 
with 
being 
criticized 
or rejected 
in 
social situations. 
5. 
Is inhibited 
in 
new interpersonal situations because 
of 
feelings of 
inadequacy. 
6. 
Views self 
as socially inept, 
personally unappealing, 
or inferior to 
others. 
7. 
Is unusually reluctant 
to 
take 
personal risks or to 
engage 
in 
any new activities 
because 
they may prove 
embarrassing. 
Diagnostic Features 


The essential 
feature of avoidant 
personality disorder is a pervasive pattern of social 
inhibition, 
feelings of inadequacy, and hypersensitivity to negative evaluation that 
begins by early 
adulthood and is present in a variety of contexts. 


Individuals with avoidant 
personality disorder avoid work activities that 
involve significant 
interpersonal 
contact 
because of fears of criticism, disapproval, or rejection (Criterion 1). Offers 
of job promotions may be declined because failure to manage the new responsibilities might 
result 
in criticism 
from 
coworkers. These individuals avoid making new friends unless they are 
certain they will 
be liked and accepted without 
criticism 
(Criterion 2). Until 
they pass stringent 
tests proving the contrary, other people are assumed to be critical 
and disapproving. Individuals 
with this disorder are highly avoidant 
of group activities. Interpersonal 
intimacy is often difficult 
for these individuals, although they are able to establish intimate relationships when there is 
assurance of uncritical 
acceptance. They may act 
with restraint, be reluctant 
to talk about 
themselves, and withhold intimate feelings for fear of being exposed, ridiculed, or shamed 
(Criterion 3). 


Because individuals with this disorder are preoccupied with being criticized or rejected in 
social 
situations, they may have a markedly low threshold for detecting such reactions (Criterion 
4). If someone is even slightly disapproving or critical, they may feel 
extremely hurt. They tend 
to be shy, quiet, inhibited, and  invisible  because of the fear that 
any attention would be critical 
or rejecting. They expect 
that 
no matter what 
they say, others will 
see it 
as  wrong,  and so they 
may say nothing at 
all. They react 
strongly to subtle cues that 
are suggestive of mockery or 
derision, and may misinterpret 
a neutral 
gesture or statement 
as critical 
or rejecting. Despite their 
longing to be active participants in social 
life, they fear placing their psychological 
welfare in the 
hands of others. Individuals with avoidant 
personality disorder are inhibited in new interpersonal 
situations because they feel 
inadequate and have low self-esteem 
(Criterion 5). These individuals 
believe themselves to be socially inept, personally unappealing, or inferior to others (Criterion 
6). Doubts concerning social 
competence and personal 
appeal 
may be most 
intense for some 
individuals in settings involving interactions with strangers. But 
many others report 
more 



difficulties with repeated interaction, when sharing of personal 
information would normally 
occur, thus, in the individual s perception, increasing the chances that 
their inferiority would be 
revealed and that 
they would be rejected. When commencing a new ongoing social 
or 
occupational 
commitment 
requiring repeated interpersonal 
interaction, individuals may over 
weeks or months develop a growing conviction that 
others or colleagues view them 
as inferior or 
lacking worth, resulting in intolerable distress or anxiety that 
prompts resignation. Thus, a 
history of repeated job changes may be present. Individuals with this disorder are unusually 
reluctant 
to take personal 
risks or to engage in any new activities because these may prove 
embarrassing (Criterion 7). They are prone to exaggerate the potential 
dangers of ordinary 
situations, and a restricted lifestyle may result from their need for certainty and security. 


Associated Features 


Individuals with avoidant 
personality disorder often vigilantly appraise the movements and 
expressions of those with whom they come into contact. They are likely to 


766 


misinterpret 
social 
responses as critical, which in turn confirms their self-doubts. They are 
described by others as being  shy,   timid,   lonely,  and  isolated.  The major problems 
associated with this disorder occur in social 
and occupational 
functioning. The low self-esteem 
and hypersensitivity to rejection are associated with restricted interpersonal 
contacts. These 
individuals may become relatively isolated and usually do not 
have a large social 
support 
network that 
can help them 
weather crises. They desire affection and acceptance and may 
fantasize about 
idealized relationships with others. Avoidant 
behaviors can also adversely affect 
occupational 
functioning because these individuals try to avoid the types of social 
situations that 
may be important for meeting the basic demands of the job or for advancement. 


Individuals with avoidant 
personality disorder have been reported as having insecure 
attachment 
styles characterized by a desire for emotional 
attachment 
(which may include a 
preoccupation with previous and current 
relationships), but 
their fears that 
others may not 
value 
them 
or may hurt 
them 
may lead them 
to respond with passivity, anger, or fear. These attachment 
patterns have been referred to variously as  preoccupied  or  fearful  depending on the model 
employed by researchers. 


Prevalence 


The estimated prevalence of avoidant personality disorder based on a probability subsample from 
Part 
II of the National 
Comorbidity Survey Replication was 5.2%. The prevalence of avoidant 
personality disorder in the National 
Epidemiologic Survey on Alcohol 
and Related Conditions 
was 2.4%. A review of six epidemiological 
studies (four in the United States) found a median 
prevalence of 2.1%. 


Development and Course 


The avoidant 
behavior often starts in infancy or childhood with shyness, isolation, and fear of 
strangers and new situations. Although shyness in childhood is a common precursor of avoidant 
personality disorder, in most 
individuals it 
tends to gradually dissipate as they get 
older. In 



contrast, individuals who go on to develop avoidant 
personality disorder may become 
increasingly shy and avoidant 
during adolescence and early adulthood, when social 
relationships 
with new people become especially important. There is some evidence that 
in adults, avoidant 
personality disorder tends to become less evident 
or to remit 
with age; 
the prevalence in adults 
older than 65 years has been estimated at 
0.8%. This diagnosis should be used with great 
caution 
in children and adolescents, for whom 
shy and avoidant 
behavior may be developmentally 
appropriate. 


Culture-Related Diagnostic Issues 


There may be variation in the degree to which different 
cultural 
and ethnic groups regard 
diffidence and avoidance as appropriate. Moreover, avoidant 
behavior may be the result 
of 
problems in acculturation following migration. In some sociocultural contexts, marked avoidance 
might 
occur following social 
embarrassment 
( loss of face ) or failure to meet 
major life goals 
rather than temperamental 
shyness. In these settings, the goal 
of avoidance includes deliberate 
minimization of social interactions in order to preserve social harmony or prevent public offense. 


Sex- and Gender-Related Diagnostic Issues 


Avoidant 
personality disorder appears to be more common in women than in men in community 
surveys. This gender difference in prevalence is small 
but 
consistently found in large population-
based samples. 


767 


Differential 
Diagnosis 


Social 
anxiety 
disorder. 
There appears to be a great 
deal 
of overlap between avoidant 
personality 
disorder and social 
anxiety disorder. It 
has been suggested that 
they may represent 
different 
manifestations of similar underlying problems, or avoidant 
personality disorder may be a more 
severe form 
of social 
anxiety disorder. However, differences have also been described, especially 
in relation to self-concept 
(such as self-esteem 
and the sense of inferiority in avoidant 
personality 
disorder); 
the latter is indirect 
evidence as it 
shows that 
negative self-concept 
in social 
anxiety 
disorder may be unstable and thus less pervasive and entrenched than in avoidant 
personality 
disorder. Additionally, studies have shown that 
avoidant 
personality disorder frequently occurs 
in the absence of social 
anxiety disorder, and some separate risk factors have been identified, 
providing support for retaining two separate diagnostic categories. 


Agoraphobia. 
Avoidance characterizes both avoidant 
personality disorder and agoraphobia, and 
they often co-occur. They can be distinguished by the motivation for the avoidance (e.g., fear of 
panic or physical harm in agoraphobia). 
Other personality 
disorders 
and 
personality 
traits. 
Other personality disorders may be confused with 


avoidant 
personality disorder because they have certain features in common. It 
is, therefore, 
important 
to distinguish among these disorders based on differences in their characteristic 
features. However, if an individual 
has personality features that 
meet 
criteria for one or more 
personality disorders in addition to avoidant 
personality disorder, all 
can be diagnosed. Both 
avoidant 
personality disorder and dependent 
personality disorder are characterized by feelings of 



inadequacy, hypersensitivity to criticism, and a need for reassurance. Similar behaviors (e.g., 
unassertiveness) and attributes (e.g., low self-esteem 
and low self-confidence) may be observed 
in both dependent 
personality disorder and avoidant 
personality disorder, although other 
behaviors are notably divergent, such as avoidance of social 
proximity in avoidant 
personality 
disorder but 
proximity-seeking in dependent 
personality disorder. The motivations behind 
similar behaviors may be quite different. For example, the unassertiveness in avoidant 
personality disorder is described as more closely related to fears of being rejected or humiliated, 
whereas in dependent 
personality disorder it 
is motivated by the desire to avoid being left 
to fend 
for oneself. However, avoidant 
personality disorder and dependent 
personality disorder may be 
particularly likely to co-occur. Like avoidant 
personality disorder, schizoid personality disorder 
and schizotypal 
personality disorder are characterized by social 
isolation. However, individuals 
with avoidant 
personality disorder want 
to have relationships with others and feel 
their loneliness 
deeply, whereas those with schizoid or schizotypal 
personality disorder may be content 
with and 
even prefer their social 
isolation. Paranoid personality disorder and avoidant 
personality disorder 
are both characterized by a reluctance to confide in others. However, in avoidant 
personality 
disorder, this reluctance is attributable more to a fear of humiliation or being found inadequate 
than to a fear of others  malicious intent. 


Many individuals display avoidant 
personality traits. Only when these traits are inflexible, 
maladaptive, and persisting and cause significant 
functional 
impairment 
or subjective distress do 
they constitute avoidant personality disorder. 
Personality 
change 
due 
to 
another medical 
condition. 
Avoidant 
personality disorder must 
be 


distinguished from 
personality change due to another medical 
condition, in which the traits that 


emerge are a direct physiological consequence of another medical condition. 
Substance 
use 
disorders. 
Avoidant 
personality disorder must 
also be distinguished from 
symptoms that may develop in association with persistent substance use. 


768 


Comorbidity 


Other disorders that 
are commonly diagnosed with avoidant 
personality disorder include 
depressive disorders and anxiety disorders, especially social 
anxiety disorder. Avoidant 
personality disorder also tends to be diagnosed with schizoid personality disorder. Avoidant 
personality disorder is associated with increased rates of substance use disorders at 
a similar rate 
to the generalized form of social anxiety disorder. 


Dependent Personality Disorder 


Diagnostic Criteria 
F60.7 


A 
pervasive 
and 
excessive 
need 
to 
be 
taken 
care 
of 
that 
leads to 
submissive 
and 
clinging 
behavior and 
fears of 
separation, 
beginning 
by early adulthood 
and 
present 
in 
a 
variety of 
contexts, 
as indicated 
by five 
(or more) of 
the 
following: 



Di 


T 
taken 
begi 
behavi 
funct 


deci 
excessi 
be 
assum 
typi 
shoul 
parent 
spend 
assum 
assi 
persons). 
condi 
what 


oft 
they 
agree 


 
 
 
 
 
 
 
 
 
 
 
 
779 



Paraphilic Disorders 


Paraphilic disorders 
included in this manual 
are voyeuristic disorder (spying on others 
in private activities), exhibitionistic disorder (exposing the genitals), frotteuristic disorder 
(touching or rubbing against 
a nonconsenting person), sexual 
masochism 
disorder (undergoing 
humiliation, bondage, or suffering), sexual 
sadism 
disorder (inflicting humiliation, bondage, or 
suffering), pedophilic disorder (sexual 
focus on children), fetishistic disorder (using nonliving 
objects or having a highly specific focus on nongenital 
body parts), and transvestic disorder 
(engaging in sexually arousing cross-dressing). These disorders have traditionally been selected 
for specific listing and assignment 
of explicit 
diagnostic criteria in DSM for two main reasons: 
they are relatively common, in relation to other paraphilic disorders, and some of them 
entail 
actions for their satisfaction that, because of their noxiousness or potential 
harm 
to others, are 
classed as criminal 
offenses. The eight 
listed disorders do not 
exhaust 
the list 
of possible 
paraphilic disorders. Many dozens of distinct 
paraphilias have been identified and named, and 
almost 
any of them 
could, by virtue of its negative consequences for the individual 
or for others, 
rise to the level of a paraphilic disorder. 


In this chapter, the order of presentation of the listed paraphilic disorders generally 
corresponds to common classification schemes for these conditions. The first 
group of disorders 
is based on anomalous activity preferences. 
These disorders are subdivided into courtship 
disorders, 
which resemble distorted components of human courtship behavior (voyeuristic 
disorder, exhibitionistic disorder, and frotteuristic disorder), and algolagnic disorders, 
which 
involve pain and suffering (sexual 
masochism 
disorder and sexual 
sadism 
disorder). The second 
group of disorders is based on anomalous target 
preferences. 
These disorders include one 
directed at 
other humans (pedophilic disorder) and two directed elsewhere (fetishistic disorder 
and transvestic disorder). 


The term 
paraphilia 
denotes any intense and persistent 
sexual 
interest 
other than sexual 
interest 
in genital 
stimulation or preparatory fondling with phenotypically normal, physically 
mature, consenting human partners. In some circumstances, the criteria  intense and persistent  
may be difficult 
to apply, such as in the assessment 
of persons who are very old or medically ill 
and who may not 
have  intense  sexual 
interests of any kind. In such circumstances, the term 
paraphilia 
may be defined as any sexual 
interest 
greater than or equal 
to nonparaphilic sexual 
interests. There are also specific paraphilias that 
are generally better described as preferential 
sexual interests than as intense sexual interests. 


Some paraphilias primarily concern the individual s erotic activities, and others primarily 
concern the individual s erotic targets. Examples of the former would include intense and 
persistent 
interests in spanking, whipping, cutting, binding, or strangulating another person, or an 
interest 
in these activities that 
equals or exceeds the individual s interest 
in copulation or 
equivalent 
interaction with another person. Examples of the latter would include intense or 
preferential 
sexual 
interest 
in children, corpses, or amputees (as a class), as well 
as intense or 



preferential 
interest 
in nonhuman animals, such as horses or dogs, or in inanimate objects, such 
as shoes or articles made of rubber. An individual s pattern of paraphilic interests is often 
reflected in his or her choice of pornography. 


780 


A paraphilic disorder 
is a paraphilia that 
is currently causing distress or impairment 
to the 
individual 
or a paraphilia whose satisfaction has entailed personal 
harm, or risk of harm, to 
others. A paraphilia is a necessary but 
not 
a sufficient 
condition for having a paraphilic disorder, 
and a paraphilia by itself does not necessarily justify or require clinical intervention. 


In the diagnostic criteria set 
for each of the listed paraphilic disorders, Criterion A specifies 
the qualitative nature of the paraphilia (e.g., an erotic focus on children or on exposing the 
genitals to strangers), and Criterion B 
specifies the negative consequences of the paraphilia (i.e., 
distress, impairment, or harm 
to others). In keeping with the distinction between paraphilias and 
paraphilic disorders, the term 
diagnosis 
should be reserved for individuals whose paraphilic 
interests or behaviors meet 
both Criteria A and B 
(i.e., individuals who have a paraphilic 
disorder). If an individual s paraphilic interests or behaviors meet 
Criterion A but 
not 
Criterion B 
for a particular paraphilia a circumstance that 
might 
arise when a benign paraphilia is 
discovered during the clinical 
investigation of some other condition then the individual 
may be 
said to have that paraphilia but not a paraphilic disorder. 


It 
is not 
rare for an individual 
to manifest 
two or more paraphilias. In some cases, the 
paraphilic foci 
are closely related and the connection between the paraphilias is intuitively 
comprehensible (e.g., foot 
fetishism 
and shoe fetishism). In other cases, the connection between 
the paraphilias is not 
obvious, and the presence of multiple paraphilias may be coincidental 
or 
else related to some generalized vulnerability to anomalies of psychosexual 
development. In any 
event, comorbid diagnoses of separate paraphilic disorders may be warranted if more than one 
paraphilia is causing suffering to the individual or harm to others. 


Because of the two-pronged nature of diagnosing paraphilic disorders, clinician-rated or self-
rated measures and severity assessments could address either the strength of the paraphilia itself 
or the seriousness of its consequences. Although the distress and impairment 
stipulated in the 
Criterion B 
are special 
in being the immediate or ultimate result 
of the paraphilia and not 
primarily the result 
of some other factor, the phenomena of reactive depression, anxiety, guilt, 
poor work history, impaired social 
relations, and so on are not 
unique in themselves and may be 
quantified with multipurpose measures of psychosocial functioning or quality of life. 


Voyeuristic Disorder 


Diagnostic Criteria 
F65.3 


A. 
Over a 
period 
of 
at 
least 
6 
months, 
recurrent 
and 
intense 
sexual arousal from 
observing 
an 
unsuspecting 
person 
who 
is naked, 
in 
the 
process of 
disrobing, 
or 
engaging 
in 
sexual activity, 
as manifested 
by fantasies, 
urges, 
or behaviors. 
B. 
The 
individual has acted 
on 
these 
sexual urges with 
a 
nonconsenting 
person, 
or 

the 
sexual urges or fantasies cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 


C. 
The 
individual experiencing 
the 
arousal and/or acting 
on 
the 
urges is at 
least 
18 
years of 
age. 
Specify 
if: 
In 
a 
controlled 
environment: 
This specifier is primarily applicable 
to 
individuals 
living 
in 
institutional or other settings where 
opportunities to 
engage 
in 
voyeuristic behavior are 
restricted. 


In 
full 
remission: 
The 
individual has not 
acted 
on 
the 
urges with 
a 
nonconsenting 
person, 
and 
there 
has been 
no 
distress or impairment 
in 
social, 
occupational, 
or other areas of 
functioning, 
for at 
least 
5 
years while 
in 
an 
uncontrolled 
environment. 


781 


Specifiers 


The  in full 
remission  specifier does not 
address the continued presence or absence of 
voyeurism per se, which may still be present after behaviors and distress have remitted. 


Diagnostic Features 


The diagnostic criteria for voyeuristic disorder can apply both to individuals who more or less 
freely disclose this paraphilic interest 
and to those who categorically deny any sexual 
arousal 
from 
observing an unsuspecting person who is naked, disrobing, or engaged in sexual 
activity 
despite substantial 
objective evidence to the contrary. If disclosing individuals also report 
distress or psychosocial 
problems because of their voyeuristic sexual 
preferences, they could be 
diagnosed with voyeuristic disorder. On the other hand, if they declare no distress, demonstrated 
by lack of anxiety, obsessions, guilt, or shame, about 
these paraphilic impulses and are not 
impaired in other important 
areas of functioning because of this sexual 
interest, and their 
psychiatric or legal 
histories indicate that 
they do not 
act 
on it, they could be ascertained as 
having voyeuristic sexual interest but should not be diagnosed with voyeuristic disorder. 


Nondisclosing individuals include, for example, individuals known to have been spying 
repeatedly on unsuspecting persons who are naked or engaging in sexual 
activity on separate 
occasions but 
who deny any urges or fantasies concerning such sexual 
behavior, and who may 
report 
that 
known episodes of watching unsuspecting naked or sexually active persons were all 
accidental 
and nonsexual. Others may disclose past 
episodes of observing unsuspecting naked or 
sexually active persons but 
contest 
any significant 
or sustained sexual 
interest 
in this behavior. 
Since these individuals deny having fantasies or impulses about 
watching others nude or 
involved in sexual 
activity, it 
follows that 
they would also reject 
feeling subjectively distressed 
or socially impaired by such impulses. Despite their nondisclosing stance, such individuals may 
be diagnosed with voyeuristic disorder. Recurrent 
voyeuristic behavior constitutes sufficient 
support 
for voyeurism 
(by fulfilling Criterion A) and simultaneously demonstrates that 
this 
paraphilically motivated behavior is causing harm to others (by fulfilling Criterion B). 


 Recurrent  spying on unsuspecting persons who are naked or engaging in sexual 
activity 



may be interpreted as requiring multiple victims, each on a separate occasion; 
this requirement 
for multiple victims on separate occasions is relevant 
because it 
increases the confidence in the 
clinical 
inference that 
the individual 
is motivated by voyeuristic disorder. Fewer victims can be 
interpreted as satisfying this criterion if there were multiple occasions of watching the same 
victim 
or if there is corroborating evidence of a distinct 
or preferential 
interest 
in secret 
watching 
of naked or sexually active unsuspecting persons. Note that 
multiple victims, as suggested 
earlier, are a sufficient 
but 
not 
a necessary condition for diagnosis; 
the criteria may also be met 
if 
the individual acknowledges intense voyeuristic sexual interest. 


Adolescence and puberty generally increase sexual 
curiosity and activity. To reduce the risk 
of pathologizing normative sexual 
interest 
and behavior during pubertal 
adolescence, the 
minimum age for the diagnosis of voyeuristic disorder is 18 years (Criterion C). 


Prevalence 


The population prevalence of individuals whose presentations meet 
the full 
criteria for 
voyeuristic disorder is unknown. Voyeuristic acts, however, are the most 
common of potentially 
law-breaking sexual 
behaviors. For example, in a Quebec Internet 
and phone survey sample, the 
lifetime prevalence of voyeuristic behaviors was reported to be as high as 34.5% (50.3% in men, 
21.2% in women). Because this same study found that 
an  intense desire  and  persistent 
behavior  occur with much less frequency (9.6% and 2.1%, respectively), the prevalence of 
voyeuristic disorder is likely much lower. The ratio of voyeuristic behavior in men to women 
was approximately 2:1 in the Quebec sample and 3:1 in a Swedish general 
population sample. In 
a study determining which particular disorders were prevalent 


782 


in individuals incarcerated for sexual 
offenses, a study of 1,346 incarcerated sex offenders from 
Austria found a prevalence of voyeuristic disorder of 3.7%. 


Development and Course 


Adult 
men with voyeuristic disorder often first 
become aware of their sexual 
interest 
in secretly 
watching unsuspecting persons during adolescence. However, the minimum 
age for a diagnosis 
of voyeuristic disorder is 18 years because there is substantial 
difficulty in differentiating it 
from 
age-appropriate puberty-related sexual 
curiosity and activity. The persistence of voyeurism 
over 
time is unclear. With or without 
treatment 
of voyeuristic disorder, the subjective distress (e.g., 
guilt, shame, intense sexual 
frustration, loneliness) or impairment 
from 
the disorder may change 
over time, as may a number of factors that 
may potentially affect 
the course of the disorder, such 
as psychiatric morbidity, hypersexuality, and sexual 
impulsivity. Thus, the severity and course 
may vary over time. As with other sexual 
preferences, advancing age may be associated with 
decreasing voyeuristic sexual preferences and behavior. 


Risk and Prognostic Factors 


Temperamental. 
Because voyeurism 
is a necessary precondition for voyeuristic disorder, risk 
factors for voyeurism should also increase the risk of voyeuristic disorder. 


Environmental. 


Childhood sexual 
abuse, substance misuse, and sexual 



preoccupation/hypersexuality have been suggested as risk factors, although the causal 
relationship to voyeuristic behavior is uncertain and the specificity unclear. 


Sex- and Gender-Related Diagnostic Issues 


Voyeuristic disorder is very uncommon among women in clinical 
settings, whereas the ratio in 
men to women for single sexually arousing voyeuristic acts is less extreme and may be 2:1 3:1. 


Differential 
Diagnosis 


Voyeurism. 
Individuals with voyeurism 
experience recurrent, intense sexual 
arousal 
from 
the act 
of observing an unsuspecting person who is naked, in the process of disrobing, or engaging in 
sexual 
activity. Unless the individual 
acts on these urges with an unsuspecting person (e.g., 
surreptitiously peeping through a neighbor s window) or unless there is accompanying clinically 
significant 
distress or impairment 
in social, occupational, or other important 
areas of functioning, 
a diagnosis of voyeuristic disorder is not warranted. 


Manic 
episode, 
major neurocognitive 
disorder, 
intellectual 
developmental 
disorder, 
personality 
change 
due 
to 
another medical 
condition, 
substance 
intoxication, 
and 
schizophrenia. 


Individuals with a major neurocognitive disorder, intellectual 
developmental 
disorder, 
personality change due to another medical 
condition, or schizophrenia, or who are in a manic 
episode or experiencing substance intoxication, may become sexually disinhibited or have 
impaired judgment 
or impulse control 
and engage in voyeuristic behavior. Unless that 
behavior 
occurs at 
times other than in the context 
of one of these disorders, a diagnosis of voyeuristic 
disorder should not be made. 


Conduct 
disorder and 
antisocial 
personality 
disorder. 


Conduct 
disorder in adolescents and antisocial 
personality disorder would be characterized by additional 
norm-breaking and antisocial 
behaviors, and the specific sexual 
interest 
in secretly watching unsuspecting others who are 
naked or engaging in sexual activity will usually be lacking. 


Comorbidity 


Known comorbidities in voyeuristic disorder are largely based on research with males suspected 
of or convicted for acts involving the secret watching of unsuspecting nude or 


783 


sexually active persons. Hence, these comorbidities might 
not 
apply to all 
individuals with 
voyeuristic disorder. Conditions that 
occur comorbidly with voyeuristic disorder include 
hypersexuality and other paraphilic disorders, particularly exhibitionistic disorder. Depressive, 
bipolar, anxiety, and substance use disorders; 
attention-deficit/hyperactivity disorder; 
and 
conduct disorder and antisocial personality disorder are also frequent comorbid conditions. 


Exhibitionistic Disorder 


F65.2Diagnostic Criteria

A. 
Over a 
period 
of 
at 
least 
6 
months, 
recurrent 
and 
intense 
sexual arousal from the 
exposure 
of 
one s genitals to 
an 
unsuspecting 
person, 
as manifested 
by 
fantasies, 
urges, 
or behaviors. 
B. 
The 
individual has acted 
on 
these 
sexual urges with 
a 
nonconsenting 
person, 
or 
the 
sexual urges or fantasies cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Specify 
whether: 


Sexually 
aroused 
by 
exposing 
genitals 
to 
prepubertal 
children 
Sexually 
aroused 
by 
exposing 
genitals 
to 
physically 
mature 
individuals 
Sexually 
aroused 
by 
exposing 
genitals 
to 
prepubertal 
children 
and 
to 


physically 
mature 
individuals 


Specify 
if: 
In 
a 
controlled 
environment: 
This specifier is primarily applicable 
to 
individuals 


living 
in 
institutional or other settings where 
opportunities to 
expose 
one s 
genitals are 
restricted. 
In 
full 
remission: 
The 
individual has not 
acted 
on 
the 
urges with 
a 


nonconsenting 
person, 
and 
there 
has been 
no 
distress or impairment 
in 
social, 
occupational, 
or other areas of 
functioning, 
for at 
least 
5 
years while 
in 
an 
uncontrolled 
environment. 


Subtypes 


The subtypes for exhibitionistic disorder are based on the age or physical 
maturity of the 
nonconsenting persons to whom 
the individual 
prefers to expose his or her genitals. The 
nonconsenting persons could be prepubescent children, adults, or both. This specifier should help 
draw adequate attention to characteristics of victims of individuals with exhibitionistic disorder 
to prevent 
co-occurring pedophilic disorder from 
being overlooked. However, indications that 
the individual 
with exhibitionistic disorder is sexually attracted to exposing his or her genitals to 
children should not preclude a diagnosis of pedophilic disorder. 


Specifiers 


The  in full 
remission  specifier does not 
address the continued presence or absence of 
exhibitionism per se, which may still be present after behaviors and distress have remitted. 


Diagnostic Features 


The diagnostic criteria for exhibitionistic disorder can apply both to individuals who more or less 
freely disclose this paraphilia and to those who categorically deny any sexual 
arousal 
from 
exposing their genitals to unsuspecting persons despite substantial 
objective evidence to the 
contrary. If disclosing individuals also report 
psychosocial 
difficulties because of their sexual 
attractions or preferences for exposing, they may be diagnosed with exhibitionistic 


784 



disorder. In contrast, if they declare no distress (exemplified by absence of anxiety, obsessions, 
and guilt 
or shame about 
these paraphilic impulses) and are not 
impaired by this sexual 
interest 
in other important 
areas of functioning, and their self-reported, psychiatric, or legal 
histories 
indicate that 
they do not 
act 
on them, they could be ascertained as having exhibitionistic sexual 
interest but 
not be diagnosed with exhibitionistic disorder. 


Examples of nondisclosing individuals include those who have exposed themselves 
repeatedly to unsuspecting persons on separate occasions but 
who deny any urges or fantasies 
about 
such sexual 
behavior and who report 
that 
known episodes of exposure were all 
accidental 
and nonsexual. Others may disclose past 
episodes of sexual 
behavior involving genital 
exposure 
but 
refute any significant 
or sustained sexual 
interest 
in such behavior. Since these individuals 
deny having urges or fantasies involving genital 
exposure, it 
follows that 
they would also deny 
feeling subjectively distressed or socially impaired by such impulses. Such individuals may be 
diagnosed with exhibitionistic disorder despite their negative self-report. Recurrent 
exhibitionistic behavior constitutes sufficient 
support 
for exhibitionism 
(Criterion A) and 
simultaneously demonstrates that 
this paraphilically motivated behavior is causing harm 
to 
others (Criterion B). 


 Recurrent  genital 
exposure to unsuspecting others may be interpreted as requiring multiple 
victims, each on a separate occasion; 
this requirement 
for multiple victims on separate occasions 
is relevant 
because it 
increases the confidence in the clinical 
inference that 
the individual 
is 
motivated by exhibitionistic disorder. Fewer victims can be interpreted as satisfying this criterion 
if there were multiple occasions of exposure to the same victim, or if there is corroborating 
evidence of a strong or preferential 
interest 
in genital 
exposure to unsuspecting persons. Note 
that 
multiple victims, as suggested earlier, are a sufficient 
but 
not 
a necessary condition for 
diagnosis, as criteria may be met 
by an individual s acknowledging intense exhibitionistic sexual 
interest with distress or impairment. 


Prevalence 


The population prevalence of individuals whose presentations meet 
the full 
criteria for 
exhibitionistic disorder is unknown, although the disorder is highly unusual 
in women. 
Exhibitionistic acts, however, are not 
uncommon, and single sexually arousing exhibitionistic 
acts occur up to half as often among women compared with men. In a Quebec Internet 
and phone 
survey sample, lifetime prevalence of exhibitionistic behaviors was reported to be 30.9% (32.6% 
in men, 29.4% in women). Because this same study found that an  intense desire  and  persistent 
behavior  occur with much less frequency (4.8% and 0.8%, respectively), the prevalence of 
exhibitionistic disorder is likely much lower. For example, a Swedish study suggested that 
the 
lifetime prevalence of exhibitionistic disorder in the general 
population was 4.1% in men and 
2.1% in women. 


Development and Course 


Adult 
men with exhibitionistic disorder often report 
that 
they first 
became aware of sexual 
interest 
in exposing their genitals to unsuspecting persons during adolescence, at 
a somewhat 
later time than the typical 
development 
of normative sexual 
interest 
in women or men. Although 
there is no minimum 
age requirement 
for the diagnosis of exhibitionistic disorder, it 
may be 
difficult 
to differentiate exhibitionistic behaviors from 
age-appropriate sexual 
curiosity in 



adolescents. Whereas exhibitionistic impulses appear to emerge in adolescence or early 
adulthood, very little is known about 
persistence over time. With or without 
treatment 
of 
exhibitionistic disorder, the subjective distress (e.g., guilt, shame, intense sexual 
frustration, 
loneliness) or impairment 
from 
the disorder may change over time, as may a number of factors 
that 
may potentially affect 
the course of the disorder, such as psychiatric morbidity, 
hypersexuality, and sexual 
impulsivity. Thus, the severity and course may vary over time. As 
with other sexual 
preferences, advancing age may be associated with decreasing exhibitionistic 
sexual preferences and behavior. 


785 


Risk and Prognostic Factors 


Temperamental. 
Because exhibitionism 
is a necessary precondition for exhibitionistic disorder, 
risk factors for exhibitionism 
should also increase the risk of exhibitionistic disorder. Antisocial 
history, antisocial 
personality disorder, alcohol 
misuse, and pedophilic sexual 
preference might 
increase risk of sexual 
recidivism 
in exhibitionistic offenders. Hence, antisocial 
personality 
disorder, alcohol 
use disorder, and pedophilic interest 
may be considered risk factors for 
exhibitionistic disorder in men with exhibitionistic sexual preferences. 


Environmental. 
Childhood sexual 
and emotional 
abuse and sexual 
preoccupation/hypersexuality 
have been suggested as risk factors for exhibitionism, although the causal 
relationship to 
exhibitionism is uncertain and the specificity unclear. 


Differential 
Diagnosis 


Exhibitionism. 
Individuals with exhibitionism 
experience recurrent, intense sexual 
arousal 
from 
the act 
of exposing their genitals to an unsuspecting person. Unless the individual 
acts on these 
urges with an unsuspecting person (e.g., exposing his genitals to riders on a train) or unless there 
is accompanying clinically significant 
distress or impairment 
in social, occupational, or other 
important areas of functioning, a diagnosis of exhibitionistic disorder is not warranted. 


Manic 
episode, 
major neurocognitive 
disorder, 
intellectual 
developmental 
disorder, 
personality 
change 
due 
to 
another medical 
condition, 
substance 
intoxication, 
and 
schizophrenia. 


Individuals with a major neurocognitive disorder, intellectual 
developmental 
disorder, 
personality change due to another medical 
condition, or schizophrenia, or who are in a manic 
episode or experiencing substance intoxication, may become sexually disinhibited or have 
impaired judgment 
or impulse control 
and engage in exhibitionistic behavior. Unless that 
behavior occurs at 
times other than in the context 
of one of these disorders, a diagnosis of 
exhibitionistic disorder should not be made. 


Conduct 
disorder and 
antisocial 
personality 
disorder. 


Conduct 
disorder in adolescents and antisocial 
personality disorder would be characterized by additional 
norm-breaking and antisocial 
behaviors, and the specific sexual interest in exposing the genitals will usually be lacking. 


Comorbidity 


Known comorbidities in exhibitionistic disorder are largely based on research with individuals 
(almost 
all 
men) convicted for criminal 
acts involving genital 
exposure to nonconsenting 
persons. Hence, these comorbidities might 
not 
apply to all 
individuals who qualify for a 



diagnosis of exhibitionistic disorder. Conditions that 
occur comorbidly with exhibitionistic 
disorder at 
high rates include depressive, bipolar, anxiety, and substance use disorders; 
hypersexuality; 
attention-deficit/hyperactivity disorder; 
other paraphilic disorders; 
and antisocial 
personality disorder. 


Frotteuristic Disorder 


Diagnostic Criteria 
F65.81 


A. 
Over a 
period 
of 
at 
least 
6 
months, 
recurrent 
and 
intense 
sexual arousal from 
touching 
or rubbing 
against 
a 
nonconsenting 
person, 
as manifested 
by fantasies, 
urges, 
or behaviors. 
B. 
The 
individual has acted 
on 
these 
sexual urges with 
a 
nonconsenting 
person, 
or 
the 
sexual urges or fantasies cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
786 


Specify 
if: 
In 
a 
controlled 
environment: 
This specifier is primarily applicable 
to 
individuals 


living 
in 
institutional or other settings where 
opportunities to 
touch 
or rub 
against 
a 
nonconsenting 
person 
are 
restricted. 
In 
full 
remission: 
The 
individual has not 
acted 
on 
the 
urges with 
a 


nonconsenting 
person, 
and 
there 
has been 
no 
distress or impairment 
in 
social, 
occupational, 
or other areas of 
functioning, 
for at 
least 
5 
years while 
in 
an 
uncontrolled 
environment. 


Specifiers 


The  in remission  specifier does not 
address the continued presence or absence of frotteurism 
per se, which may still be present after behaviors and distress have remitted. 


Diagnostic Features 


The diagnostic criteria for frotteuristic disorder can apply both to individuals who relatively 
freely disclose this paraphilia and to those who firmly deny any sexual 
arousal 
from 
touching or 
rubbing against 
a nonconsenting person regardless of considerable objective evidence to the 
contrary. If disclosing individuals also report 
psychosocial 
impairment 
because of their sexual 
preferences for touching or rubbing against 
a nonconsenting person, they could be diagnosed 
with frotteuristic disorder. In contrast, if they declare no distress (demonstrated by lack of 
anxiety, obsessions, guilt, or shame) about 
these paraphilic impulses and are not 
impaired in 
other important 
areas of functioning because of this sexual 
interest, and their psychiatric or legal 
histories indicate that 
they do not 
act 
on it, they could be ascertained as having frotteuristic 



sexual interest but should not be diagnosed with frotteuristic disorder. 


Nondisclosing individuals include, for instance, individuals known to have been touching or 
rubbing against 
nonconsenting persons on separate occasions but 
who contest 
any urges or 
fantasies concerning such sexual 
behavior. Such individuals may report 
that 
identified episodes 
of touching or rubbing against 
an unwilling individual 
were all 
unintentional 
and nonsexual. 
Others may disclose past 
episodes of touching or rubbing against 
nonconsenting persons but 
contest 
any major or persistent 
sexual 
interest 
in this. Since these individuals deny having 
fantasies or impulses about 
touching or rubbing, they would consequently reject 
feeling 
distressed or psychosocially impaired by such impulses. Despite their nondisclosing position, 
such individuals may be diagnosed with frotteuristic disorder. Recurrent 
frotteuristic behavior 
constitutes satisfactory support 
for frotteurism 
(by fulfilling Criterion A) and concurrently 
demonstrates that 
this paraphilically motivated behavior is causing harm 
to others (by fulfilling 
Criterion B). 


 Recurrent  touching or rubbing against 
a nonconsenting person may be interpreted as 
requiring multiple victims, each on a separate occasion; 
this requirement 
for multiple victims on 
separate occasions is relevant 
because it 
increases the confidence in the clinical 
inference that 
the 
individual 
is motivated by frotteuristic disorder. Fewer victims can be interpreted as satisfying 
this criterion if there were multiple occasions of touching or rubbing against 
the same unwilling 
individual, or corroborating evidence of a strong or preferential 
interest 
in touching or rubbing 
against 
nonconsenting persons. Note that 
multiple victims are a sufficient 
but 
not 
a necessary 
condition for diagnosis; 
criteria may also be met 
if the individual 
acknowledges intense 
frotteuristic sexual interest with clinically significant distress and/or impairment. 


Prevalence 


The population prevalence of individuals whose presentations meet 
the full 
criteria for 
frotteuristic disorder is unknown, but frotteuristic acts, including the uninvited sexual touching of 
or rubbing against 
another individual, may occur in up to 30% of adult 
men in the U.S. and 
Canadian general population. Prevalence of frotteuristic disorder is certainly 


787 


much lower, considering the finding that 
 intense desire  and  persistent 
behavior  were 
reported infrequently (3.8% and 0.7%, respectively). In outpatient 
settings for men with 
paraphilic disorders and hypersexuality, approximately 10% 14% have a presentation that 
meets 
diagnostic criteria for frotteuristic disorder. Prevalence among women is likely lower. 


Development and Course 


Adult 
men with frotteuristic disorder often report 
first 
becoming aware of their sexual 
interest 
in 
surreptitiously touching unsuspecting persons during late adolescence or emerging adulthood. 
However, children and adolescents may also touch or rub against 
unwilling others in the absence 
of a diagnosis of frotteuristic disorder. Although there is no minimum 
age for the diagnosis, 
frotteuristic disorder can be difficult 
to differentiate from 
conduct-disordered behavior without 
sexual 
motivation in individuals at 
younger ages. The persistence of frotteurism 
over time is 
unclear. With or without 
treatment 
of frotteuristic disorder, the subjective distress (e.g., guilt, 



shame, intense sexual 
frustration, loneliness) or impairment 
from 
the disorder may change over 
time, as may a number of factors that 
may potentially affect 
the course of the disorder, such as 
psychiatric morbidity, hypersexuality, and sexual 
impulsivity. Thus, the severity and course may 
vary over time. As with other sexual 
preferences, advancing age may be associated with 
decreasing frotteuristic sexual preferences and behavior. 


Risk and Prognostic Factors 


Temperamental. 
Nonsexual antisocial behavior and sexual preoccupation/hypersexuality might be 
nonspecific risk factors, although the causal 
relationship to frotteurism 
is uncertain and the 
specificity unclear. However, because frotteurism 
is a necessary precondition for frotteuristic 
disorder, risk factors for frotteurism should also increase the risk of frotteuristic disorder. 


Differential 
Diagnosis 


Frotteurism. 
Individuals with frotteurism 
experience recurrent 
intense sexual 
arousal 
from 
the act 
of touching or rubbing against 
a nonconsenting person. Unless the individual 
acts on these urges 
with a nonconsenting person (e.g., rubbing his genitals against 
a passenger on a crowded subway 
car) or unless there is accompanying clinically significant 
distress or impairment 
in social, 
occupational, or other important 
areas of functioning, a diagnosis of frotteuristic disorder is not 
warranted. 


Manic 
episode, 
major neurocognitive 
disorder, 
intellectual 
developmental 
disorder, 
personality 
change 
due 
to 
another medical 
condition, 
substance 
intoxication, 
and 
schizophrenia. 


Individuals with a major neurocognitive disorder, intellectual 
developmental 
disorder, 
personality change due to another medical 
condition, or schizophrenia, or who are in a manic 
episode or experiencing substance intoxication, may become sexually disinhibited or have 
impaired judgment 
or impulse control 
and engage in frotteuris-tic behavior. Unless that 
behavior 
occurs at 
times other than in the context 
of one of these disorders, a diagnosis of frotteuristic 
disorder should not be made. 


Conduct 
disorder and 
antisocial 
personality 
disorder. 


Conduct 
disorder in adolescents and antisocial 
personality disorder would be characterized by additional 
norm-breaking and antisocial 
behaviors, and the specific sexual 
interest 
in touching or rubbing against 
a nonconsenting person 
will usually be lacking. 


Comorbidity 


Known comorbidities in frotteuristic disorder are largely based on research with men suspected 
of or convicted for criminal acts involving sexually motivated touching of or 


788 


rubbing against 
a nonconsenting person. Hence, these comorbidities might 
not 
apply to other 
individuals with a diagnosis of frotteuristic disorder based on subjective distress over their sexual 
interest. Conditions that 
occur comorbidly with frotteuristic disorder include hypersexuality and 
other paraphilic disorders, particularly exhibitionistic disorder and voyeuristic disorder. Conduct 
disorder, antisocial 
personality disorder, depressive disorders, bipolar disorders, anxiety 
disorders, and substance use disorders also co-occur. 



Sexual 
Masochism Disorder 


Diagnostic Criteria 
F65.51 


A. 
Over a 
period 
of 
at 
least 
6 
months, 
recurrent 
and 
intense 
sexual arousal from the 
act 
of 
being 
humiliated, 
beaten, 
bound, 
or otherwise 
made 
to 
suffer, 
as 
manifested 
by fantasies, 
urges, 
or behaviors. 
B. 
The 
fantasies, 
sexual urges, 
or behaviors cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Specify 
if: 
With 
asphyxiophilia: 
If 
the 
individual engages in 
the 
practice 
of 
achieving 
sexual arousal related 
to 
restriction 
of 
breathing. 


Specify 
if: 
In 
a 
controlled 
environment: 
This specifier is primarily applicable 
to 
individuals 


living 
in 
institutional or other settings where 
opportunities to 
engage 
in 
masochistic sexual behaviors are 
restricted. 
In 
full 
remission: 
There 
has been 
no 
distress or impairment 
in 
social, 


occupational, 
or other areas of 
functioning 
for at 
least 
5 
years while 
in 
an 
uncontrolled 
environment. 


Diagnostic Features 


The diagnostic criteria for sexual 
masochism 
disorder are intended to apply to individuals who 
freely admit 
to having such paraphilic interests. Such individuals openly acknowledge intense 
sexual 
arousal 
from 
the act 
of being humiliated, beaten, bound, or otherwise made to suffer, as 
manifested by fantasies, urges, or behaviors. If these individuals also report 
psychosocial 
difficulties because of their sexual 
attractions or preferences for being humiliated, beaten, bound, 
or otherwise made to suffer, they may be diagnosed with sexual 
masochism 
disorder. In contrast, 
if they declare no distress, exemplified by anxiety, obsessions, guilt, or shame, about 
these 
paraphilic impulses, and are not 
hampered by them 
in pursuing other personal 
goals, they could 
be ascertained as having masochistic sexual 
interest 
but 
should not 
be diagnosed with sexual 
masochism disorder. 


The term 
bondage-domination-sadism-masochism 
(BDSM) is broadly used to refer to a wide 
range of behaviors that 
individuals with sexual 
masochism 
and/or sexual 
sadism 
(as well 
as other 
individuals with similar sexual 
interests) engage in, such as restraints or restriction, discipline, 
spanking, slapping, sensory deprivation (e.g., using blindfolds), and dominance-submission role-
play involving themes such as master/enslaved person, owner/pet, or kidnapper/victim. 


Associated Features 


The extensive use of pornography involving the act 
of being humiliated, beaten, bound, or 
otherwise made to suffer is sometimes an associated feature of sexual 
masochism 
disorder. 



Those who engage in sadomasochistic sexual 
behavior may experience a hyposensitivity to pain, 
although it 
is unknown whether this finding applies to those with sexual 
masochism 
disorder. 
Additionally, although it is often assumed that individuals with 


789 


masochistic sexual 
interest 
have a history of childhood sexual 
abuse experiences, there is 
insufficient evidence to support this association. 


Prevalence 


The population prevalence of individuals whose presentations meet 
the full 
criteria for sexual 
masochism 
disorder is unknown. In Australia, it 
has been estimated that 
2.2% of men and 1.3% 
of women had been involved in BDSM behavior in the past 12 months. 


Development and Course 


Individuals with paraphilias living in the community have reported a mean age at 
onset 
for 
masochism 
of 19.3 years, although earlier ages, including puberty and childhood, have also been 
reported for the onset 
of masochistic fantasies. Very little is known about 
persistence over time. 
With or without 
treatment 
of sexual 
masochism 
disorder, the subjective distress (e.g., guilt, 
shame, intense sexual 
frustration, loneliness) or impairment 
from 
the disorder may change over 
time, as may a number of factors that 
may potentially affect 
the course of the disorder, such as 
psychiatric morbidity, hypersexuality, and sexual 
impulsivity. Thus, the severity and course may 
vary over time. As with other sexual 
preferences, advancing age may be associated with 
decreasing sexual masochistic preferences and behavior. 


Culture-Related Diagnostic Issues 


It 
is important 
to distinguish self-harming behaviors that 
occur during collectively accepted 
religious and spiritual 
practices from 
sadomasochistic behavior conducted for sexual 
arousal. For 
example, collective rituals in various religions and societies include suspension from 
hooks, self-
flagellation, self-mortification, and other painful 
ordeals. The role of sexual 
arousal 
or pleasure 
in these practices remains unknown. 


Association With Suicidal 
Thoughts or Behavior 


Association of sexual 
masochism 
disorder with suicidal 
thoughts or behavior is unknown. 
However, a study of 321 adults who endorsed BDSM involvement 
found an association of 
stigma-related shame and guilt with suicidal ideation. 


Functional 
Consequences of Sexual 
Masochism Disorder 


The functional 
consequences of sexual 
masochism 
disorder are unknown. Individuals reporting 
sexual 
interest 
in asphyxiophilia seem 
to experience more sexual 
distress and psychological 
maladjustment 
than the general 
population. Individuals engaging in masochistic behavior are at 
risk for accidental 
death while practicing asphyxiophilia or other autoerotic procedures. 
However, the proportion of these decedents whose sexual 
interests and behavior fulfill 
diagnostic 



criteria for sexual masochism is unknown. 


Differential 
Diagnosis 


Sexual 
masochism. 
Individuals with sexual 
masochism 
experience recurrent, intense sexual 
arousal 
from 
the act 
of being humiliated, beaten, bound, or otherwise made to suffer. Unless the 
sexual 
urges, fantasies, or behaviors involving being humiliated or made to suffer are 
accompanied by clinically significant 
distress or impairment 
in social, occupational, or other 
important areas of functioning, a diagnosis of sexual masochism disorder is not warranted. 


Comorbidity 


Known comorbidities with sexual 
masochism 
disorder are largely based on individuals in 
treatment. Disorders that occur comorbidly with sexual masochism disorder typically 


790 


include other paraphilic disorders, such as transvestic fetishism. There is some indication of an 
association of sexual 
masochism 
disorder with borderline personality disorder (based on data 
from a small clinical sample of women with and without borderline personality disorder). 


Sexual 
Sadism Disorder 


Diagnostic Criteria 
F65.52 


A. 
Over a 
period 
of 
at 
least 
6 
months, 
recurrent 
and 
intense 
sexual arousal from the 
physical or psychological suffering 
of 
another person, 
as manifested 
by 
fantasies, 
urges, 
or behaviors. 
B. 
The 
individual has acted 
on 
these 
sexual urges with 
a 
nonconsenting 
person, 
or 
the 
sexual urges or fantasies cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Specify 
if: 
In 
a 
controlled 
environment: 
This specifier is primarily applicable 
to 
individuals 


living 
in 
institutional or other settings where 
opportunities to 
engage 
in 
sadistic 
sexual behaviors are 
restricted. 
In 
full 
remission: 
The 
individual has not 
acted 
on 
the 
urges with 
a 


nonconsenting 
person, 
and 
there 
has been 
no 
distress or impairment 
in 
social, 
occupational, 
or other areas of 
functioning, 
for at 
least 
5 
years while 
in 
an 
uncontrolled 
environment. 


Diagnostic Features 


The diagnostic criteria for sexual 
sadism 
disorder are intended to apply both to individuals who 
freely admit 
to having such paraphilic interests and to those who deny any sexual 
interest 
in the 



physical 
or psychological 
suffering of another individual 
despite substantial 
objective evidence 
to the contrary. Individuals who openly acknowledge intense sexual 
interest 
in the physical 
or 
psychological 
suffering of others are referred to as  admitting individuals.  If these individuals 
also report 
psychosocial 
difficulties because of their sexual 
attractions or preferences for the 
physical 
or psychological 
suffering of another individual, they may be diagnosed with sexual 
sadism 
disorder. In contrast, if admitting individuals declare no distress, exemplified by anxiety, 
obsessions, guilt, or shame, about 
these paraphilic impulses, and are not 
hampered by them 
in 
pursuing other goals, and their self-reported, psychiatric, or legal 
histories indicate that 
they do 
not 
act 
on them 
with nonconsenting persons, then they could be ascertained as having sadistic 
sexual interest but their presentation would not meet criteria for sexual sadism disorder. 


Examples of individuals who deny any interest 
in the physical 
or psychological 
suffering of 
another individual 
include individuals known to have inflicted pain or suffering on multiple 
victims on separate occasions but 
who deny any urges or fantasies about 
such sexual 
behavior 
and who may further claim 
that 
known episodes of sexual 
assault 
were either unintentional 
or 
nonsexual. Others may admit 
past 
episodes of sexual 
behavior involving the infliction of pain or 
suffering on a nonconsenting person but 
do not 
report 
any significant 
or sustained sexual 
interest 
in the physical 
or psychological 
suffering of another person. Since these individuals deny having 
urges or fantasies involving sexual 
arousal 
to pain and suffering, it 
follows that 
they would also 
deny feeling subjectively distressed or socially impaired by such impulses. Such individuals may 
be diagnosed with sexual 
sadism 
disorder despite their negative self-report. Their recurrent 
behavior constitutes clinical 
support 
for the presence of the paraphilia of sexual 
sadism 
(by 
satisfying Criterion A) and simultaneously demonstrates that 
their paraphilically motivated 
behavior is causing clinically significant 
distress, harm, or risk of harm 
to others (satisfying 
Criterion B). 


791 


 Recurrent  sexual 
sadism 
involving nonconsenting others may be interpreted as requiring 
multiple victims, each on a separate occasion; 
this requirement 
for multiple victims on separate 
occasions is relevant 
because it 
increases the confidence in the clinical 
inference that 
the 
individual 
is motivated by sexual 
sadism 
disorder. Fewer victims can be interpreted as satisfying 
this criterion, if there are multiple instances of infliction of pain and suffering to the same victim, 
or if there is corroborating evidence of a strong or preferential 
interest 
in pain and suffering 
involving multiple victims. Note that 
multiple victims, as suggested earlier, are a sufficient 
but 
not 
a necessary condition for diagnosis, as the criteria may be met 
if the individual 
acknowledges 
intense sadistic sexual interest. 


The term 
bondage-domination-sadism-masochism 
(BDSM) is broadly used to refer to a wide 
range of behaviors that 
individuals with sexual 
masochism 
and/or sexual 
sadism 
(as well 
as other 
individuals with similar sexual 
interests) engage in, such as restraints or restriction, discipline, 
spanking, slapping, sensory deprivation (e.g., using blindfolds), and dominance-submission role-
play involving themes such as master/enslaved person, owner/pet, or kidnapper/victim. 


Associated Features 


The extensive use of pornography involving the infliction of pain and suffering is sometimes an 



associated feature of sexual sadism disorder. 


Prevalence 


The population prevalence of individuals whose presentations meet 
the full 
criteria for sexual 
sadism 
disorder is unknown and is largely based on individuals in forensic settings. Among 
civilly committed sexual 
offenders in the United States, less than 10% have sexual 
sadism 
disorder. Among individuals who have committed sexually motivated homicides, the proportion 
of sexually sadistic behavior is about one-third. 


Individuals with sexual sadism disorder in forensic samples are almost exclusively men, but a 
representative sample of the population in Australia reported that 
2.2% of men and 1.3% of 
women said that 
they had been involved in BDSM behavior in the previous year. In a 
population-based sample in Finland, the lifetime prevalence for sexually sadistic behavior was 
2.7% among men and 2.3% among women. 


Development and Course 


Information on the development 
and course of sexual 
sadism 
disorder is extremely limited. 
Whereas sexually sadistic preferences per se are probably a lifelong characteristic, sexual 
sadism 
disorder may fluctuate according to the individual s subjective distress or his or her propensity to 
harm 
nonconsenting others. As with other sexual 
preferences, advancing age may be associated 
with decreasing sexually sadistic preferences and behavior. Regarding sexually sadistic 
preference, many individuals who engage in BDSM behavior became aware of their 
corresponding interest in their teenage years. 


Culture-Related Diagnostic Issues 


The legal 
status of sexually sadistic behavior ranges across countries and societies, suggesting 
the potential 
for variation in distress (because of variation in cultural 
acceptance) and functional 
impairment (because of legal status). 


Association With Suicidal 
Thoughts or Behavior 


Association of sexual 
sadism 
disorder with suicidal 
thoughts or behavior is unknown. However, 
a study of 321 adults who endorsed BDSM involvement 
found an association of stigma-related 
shame and guilt with suicidal ideation. 


792 


Differential 
Diagnosis 


Sexual 
sadism. 
Individuals with sexual 
sadism 
experience recurrent, intense sexual 
arousal 
from 
the physical 
or psychological 
suffering of another person. Unless the sexual 
urges to make 
another person suffer physically or psychologically are acted on with a non-consenting person, or 
unless there is accompanying clinically significant 
distress or impairment 
in social, occupational, 
or other important 
areas of functioning, a diagnosis of sexual 
sadism 
disorder is not 
warranted. 
The majority of individuals who are active in community networks that 
practice sadistic and 
masochistic behaviors do not 
express any dissatisfaction with their sexual 
interests, and their 



behavior would not meet DSM-5 criteria for sexual sadism disorder. 


Infliction 
of 
physical 
or psychological 
suffering 
during 
the 
commission 
of 
a 
sex 
crime. 


Individuals who 
commit 
rape or other sexual 
assaults might 
inflict 
pain on their victims as a result 
of the act 
of 
rape, or in the course of subduing victims or restraining them 
to commit 
the sexual 
assault. Such 
instrumental 
infliction of pain should not 
be considered to be indicative of sexual 
sadism 
disorder unless there is evidence that 
the individual 
is deriving pleasure from 
the infliction of 
pain and the resulting suffering of the victim 
(e.g., admission of specifically being aroused by the 
pain, evidence of a preference for pornography involving themes of sexual 
sadism, excessive use 
of pain-inducing violence that 
goes beyond what 
might 
be necessary in the course of committing 
the sexual assault). 
Conduct 
disorder and 
antisocial 
personality 
disorder. 


Individuals with conduct 
disorder and 
antisocial 
personality disorder may be physically cruel 
to people and force others to engage in 
sexual 
activity. Coercive or sadistic sexual 
behaviors that 
occur in the context 
of conduct 
disorder or antisocial 
personality disorder but 
that 
do not 
reflect 
an underlying pattern of sexual 
arousal 
from 
the physical 
or psychological 
suffering of another person should not 
be used as a 
basis for diagnosing sexual 
sadism 
disorder. In cases in which the diagnostic criteria are met 
for 
both sexual 
sadism 
disorder and conduct 
disorder/antisocial 
personality disorder, both disorders 
may be diagnosed. 


Comorbidity 


Known comorbidities with sexual 
sadism 
disorder are largely based on individuals (almost 
all 
men) convicted for criminal 
acts involving sadistic acts against 
nonconsenting victims. Hence, 
these comorbidities might 
not 
apply to all 
individuals who never engaged in sadistic activity with 
a nonconsenting victim 
but 
who qualify for a diagnosis of sexual 
sadism 
disorder based on 
subjective distress over their sexual 
interest. Disorders that 
are commonly comorbid with sexual 
sadism 
disorder include other paraphilic disorders. According to a population-based study in 
Finland, individuals who had engaged in sexually sadistic behavior had also engaged in other 
types of paraphilic behavior, namely (in descending order of co-occurrence) masochism 
(68.8%), 
voyeurism (33.3%), transvestic fetishism (9.2%), and exhibitionism (6.4%). 


Pedophilic Disorder 


Diagnostic Criteria 
F65.4 


A. 
Over a 
period 
of 
at 
least 
6 
months, 
recurrent, 
intense 
sexually arousing 
fantasies, 
sexual urges, 
or behaviors involving 
sexual activity with 
a 
prepubescent 
child 
or children 
(generally age 
13 
years or younger). 
B. 
The 
individual has acted 
on 
these 
sexual urges, 
or the 
sexual urges or fantasies 
cause 
marked 
distress or interpersonal difficulty. 
793 



C. 
The 
individual is at 
least 
age 
16 
years and 
at 
least 
5 
years older than 
the 
child 
or 
children 
in 
Criterion 
A. 
Note: 
Do 
not 
include 
an 
individual in 
late 
adolescence 
involved 
in 
an 
ongoing 
sexual relationship 
with 
a 
12- or 13-year-old. 


Specify 
whether: 
Exclusive 
type 
(attracted 
only to 
children) 
Nonexclusive 
type 


Specify 
if: 


Sexually 
attracted 
to 
males 
Sexually 
attracted 
to 
females 
Sexually 
attracted 
to 
both 


Specify 
if: 


Limited 
to 
incest 


Diagnostic Features 


The diagnostic criteria for pedophilic disorder are intended to apply both to individuals who 
freely disclose this paraphilia and to individuals who deny any sexual 
attraction to prepubertal 
children (generally age 13 years or younger), despite substantial 
objective evidence to the 
contrary. The age guideline of 13 or younger is approximate only, because the onset 
of puberty 
varies from 
person to person, and there is good evidence the average age at 
onset 
of puberty has 
been declining over time and differs across ethnicities and cultures. Examples of disclosing this 
paraphilia include candidly acknowledging an intense sexual 
interest 
in children and indicating 
that 
sexual 
interest 
in children is greater than or equal 
to sexual 
interest 
in physically mature 
persons. If individuals also complain that 
their sexual 
attractions or preferences for children are 
causing marked distress or psychosocial 
difficulties, they may be diagnosed with pedophilic 
disorder. However, if they report 
an absence of feelings of guilt, shame, or anxiety about 
these 
impulses and are not 
functionally limited by their paraphilic impulses (according to self-report, 
objective assessment, or both), and their self-reported and legally recorded histories indicate that 
they have never acted on their impulses, then these individuals have a pedophilic sexual 
interest 
but 
not 
pedophilic disorder. When trying to differentiate child offenders with pedophilic disorder 
from 
child offenders without 
pedophilic disorder, factors that 
suggest 
a diagnosis of pedophilic 
disorder in the offender include self-reported interest 
in children, use of child pornography, a 
history of multiple child victims, boy victims, and unrelated child victims. 


Examples of individuals who deny attraction to children include individuals who are known 
to have sexually approached multiple children on separate occasions but 
who deny any urges or 
fantasies about 
sexual 
behavior involving children, and who may further claim 
that 
the known 
episodes of physical 
contact 
were all 
unintentional 
and nonsexual. Other individuals may 
acknowledge past 
episodes of sexual 
behavior involving children but 
deny any significant 
or 
sustained sexual 
interest 
in children. Because these individuals may deny experiences, impulses, 
or fantasies involving children, they may also deny feeling subjectively distressed. Such 
individuals may still 
be diagnosed with pedophilic disorder despite the absence of self-reported 



distress, provided that 
there is evidence of recurrent 
behaviors persisting for 6 months (Criterion 


A) and evidence that 
the individual 
has acted on sexual 
urges or experienced interpersonal 
difficulties as a consequence of the disorder (Criterion B). Behaviors include sexual 
interactions 
with children, whether or not 
they involve physical 
contact 
(e.g., some pedophilic individuals 
expose themselves to children). Although the use of sexually explicit 
content 
depicting 
prepubescent 
children is typical 
of individuals with pedophilic sexual 
interests and thus might 
contribute important 
information relevant 
to the evaluation of Criterion A, such behavior in the 
absence of the individual s sexual 
interactions with children (i.e., acting on these sexual 
urges in 
person) is insufficient to conclude that Criterion B is met. 
794 


Presence of multiple victims, as discussed above, is sufficient 
but 
not 
necessary for 
diagnosis; 
that 
is, the individual 
can still 
meet 
Criterion A by merely acknowledging intense or 
preferential sexual interest in children. 


Associated Features 


Individuals with pedophilic disorder may experience an emotional 
and cognitive affinity with 
children, sometimes referred to as emotional 
congruence 
with children. Emotional 
congruence 
with children can manifest 
in different 
ways, including preferring social 
interactions with 
children over adults, feeling like one has more in common with children than with adults, and 
choosing occupations or volunteer roles in order to be around children more often. Studies show 
that 
emotional 
congruence with children is related to both pedophilic sexual 
interest 
and the 
likelihood of sexually reoffending among individuals who have sexually offended. 


Prevalence 


The population prevalence of individuals whose presentations meet 
the full 
criteria for 
pedophilic disorder is unknown but 
is likely less than 3% among men in international 
studies. 
The population prevalence of pedophilic disorder in women is even more uncertain, but 
it 
is 
likely a small fraction of the prevalence in men. 


Development and Course 


Adult 
men with pedophilic disorder may indicate that 
they became aware of strong or 
preferential 
sexual 
interest 
in children around the time of puberty the same time frame in which 
men who later prefer physically mature partners became aware of their sexual 
interest 
in women 
or men. Attempting to diagnose pedophilic disorder at 
the age at 
which it 
first 
manifests is 
problematic because of the difficulty during adolescent 
development 
in differentiating it 
from 
age-appropriate sexual 
interest 
in peers or from 
sexual 
curiosity. Hence, Criterion C 
requires for 
diagnosis a minimum 
age of 16 years and at 
least 
5 years older than the child or children in 
Criterion A. 


Pedophilia per se appears to be a lifelong condition. Pedophilic disorder, however, 
necessarily includes other elements that 
may change over time with or without 
treatment: 
subjective distress (e.g., guilt, shame, intense sexual 
frustration, or feelings of isolation) or 
psychosocial 
impairment, or the propensity to act 
out 
sexually with children, or both. Therefore, 



the course of pedophilic disorder may fluctuate, or the intensity might 
increase or decrease with 
age. 


Adults with pedophilic disorder may report 
an awareness of sexual 
interest 
in children that 
preceded engaging in sexual 
behavior involving children or self-identification as an individual 
with pedophilia. Advanced age is as likely to similarly diminish the frequency of sexual 
behavior 
involving children as it does other paraphilically motivated and nonparaphilic sexual behavior. 


Risk and Prognostic Factors 


Temperamental. 
There appears to be an interaction between pedophilia and antisocial 
personality 
traits such as callousness, impulsivity, and a willingness to take risks without 
adequate regard for 
the consequences. Men with pedophilic interest 
and antisocial 
personality traits are more likely 
to act 
out 
sexually with children and thus qualify for a diagnosis of pedophilic disorder. Thus, 
antisocial 
personality disorder may be considered a risk factor for pedophilic disorder in males 
with pedophilia. 


Environmental. 
Adult 
men with pedophilia sometimes report 
that 
they were sexually abused as 
children. It 
is unclear, however, whether this correlation reflects a causal 
influence of childhood 
sexual abuse on adult pedophilia. 


795 


Genetic 
and 
physiological. 
Since pedophilia is a necessary condition for pedophilic disorder, any 
factor that 
increases the probability of pedophilia also increases the risk of pedophilic disorder. 
There is some evidence that 
neurodevelopmental 
perturbation in utero increases the probability 
of development of a pedophilic interest. 


Sex- and Gender-Related Diagnostic Issues 


Laboratory measures of sexual 
interest, in terms of psychophysiological 
responses to sexual 
stimuli 
depicting children, which are sometimes useful 
in diagnosing pedophilic disorder in men, 
are not 
necessarily useful 
in diagnosing this disorder in women because there has been very 
limited research on the assessment of pedophilic sexual interest in women. 


Diagnostic Markers 


Psychophysiological 
measures of sexual 
interest 
may sometimes be useful 
when an individual s 
history suggests the possible presence of pedophilic disorder but 
the individual 
denies strong or 
preferential 
attraction to children. The most 
thoroughly researched and longest 
used of such 
measures is penile plethysmography, although the sensitivity and specificity of diagnosis may 
vary across sites, which frequently use different 
stimuli, procedures, and scoring. Viewing time, 
using photographs of nude or minimally clothed persons as visual 
stimuli, is also used to 
diagnose pedophilic disorder, especially in combination with self-report 
measures. U.S. 
clinicians, however, should be aware that 
possession of visual 
sexual 
stimuli 
depicting children, 
even for diagnostic purposes, may violate American law regarding possession of child 
pornography and leave the clinician susceptible to criminal 
prosecution. The option exists to use 
audio stimuli 
describing sexual 
interactions in penile plethysmography. Across 
psychophysiological 
methods, the diagnostic marker is relative sexual 
response to stimuli 



depicting children compared with stimuli 
depicting adults, rather than absolute response to child 
stimuli. 


Differential 
Diagnosis 


Pedophilia. 
Individuals with pedophilia experience recurrent, intense, sexually arousing fantasies 
or sexual 
urges involving sexual 
activity with a prepubescent 
child or children. Unless the 
individual 
has acted on these sexual 
urges with a prepubescent 
child or unless the sexual 
urges or 
fantasies cause marked distress or interpersonal 
difficulty, a diagnosis of pedophilic disorder is 
not warranted. 


Other paraphilic 
disorders. 
Sometimes individuals present 
with a different 
paraphilic disorder but 
are referred for an evaluation regarding possible pedophilic disorder (e.g., when an individual 
with a diagnosis of exhibitionistic disorder exposes himself to children as well 
as adults). In 
some cases, both diagnoses may apply, whereas in others, it 
may be the case that 
one paraphilic 
disorder diagnosis is sufficient. For example, an individual 
who exposes himself exclusively to 
prepubescent 
children may have both exhibitionistic disorder and pedophilic disorder, whereas 
another individual 
who exposes himself to victims, irrespective of the victims  age, may be 
considered to have only exhibitionistic disorder. 


Antisocial 
personality 
disorder. 
Some individuals with antisocial 
personality disorder sexually 
abuse children, reflecting the fact 
that 
the presence of antisocial 
personality disorder increases 
the likelihood that 
an individual 
who is primarily attracted to mature persons will 
approach a 
child sexually, on the basis of relative access to the child. An additional 
diagnosis of pedophilic 
disorder should only be considered if there is evidence that 
over a period of at 
least 
6 months, the 
individual 
has also had recurrent, intense, sexually arousing fantasies, sexual 
urges, or behaviors 
involving sexual activity with a prepubescent child. 


796 


Substance 
intoxication. 
The disinhibiting effects of substance intoxication may also increase the 
likelihood that 
an individual 
who is primarily attracted to mature persons will 
sexually approach 
a child. 


Obsessive-compulsive 
disorder. 
There are occasional 
individuals who complain about 
egodystonic 
thoughts and worries about 
possible attraction to children. Clinical 
interviewing usually 
reveals an absence of positive feelings about 
these thoughts, no connection between these 
thoughts and sexual 
behavior (e.g., masturbating to these thoughts), and sometimes additional 
ego-dystonic, intrusive sexual ideas (e.g., concerns about homosexuality). 


Comorbidity 


Psychiatric comorbidity of pedophilic disorder includes substance use disorders; 
depressive, 
bipolar, and anxiety disorders; 
antisocial 
personality disorder; 
and other paraphilic disorders. 
However, findings on comorbid disorders are largely among individuals convicted for sexual 
offenses involving children (almost 
all 
males) and may not 
be generalizable to other individuals 
with pedophilic disorder (e.g., individuals who have never approached a child sexually but 
who 
qualify for the diagnosis of pedophilic disorder on the basis of subjective distress). 



Fetishistic Disorder 


Diagnostic Criteria 
F65.0 


A. 
Over a 
period 
of 
at 
least 
6 
months, 
recurrent 
and 
intense 
sexual arousal from 
either the 
use 
of 
nonliving 
objects or a 
highly specific focus on 
nongenital body 
part(s), 
as manifested 
by fantasies, 
urges, 
or behaviors. 
B. 
The 
fantasies, 
sexual urges, 
or behaviors cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
C. 
The 
fetish 
objects are 
not 
limited 
to 
articles of 
clothing 
used 
in 
cross-dressing 
(as 
in 
transvestic disorder) or devices specifically designed 
for the 
purpose 
of 
tactile 
genital stimulation 
(e.g., 
vibrator). 
Specify: 


Body 
part(s) 
Nonliving 
object(s) 
Other 


Specify 
if: 
In 
a 
controlled 
environment: 
This specifier is primarily applicable 
to 
individuals 


living 
in 
institutional or other settings where 
opportunities to 
engage 
in 
fetishistic 
behaviors are 
restricted. 
In 
full 
remission: 
There 
has been 
no 
distress or impairment 
in 
social, 


occupational, 
or other areas of 
functioning 
for at 
least 
5 
years while 
in 
an 
uncontrolled 
environment. 


Specifiers 


Although individuals with fetishistic disorder may report 
intense and recurrent 
sexual 
arousal 
to 
inanimate objects or a specific body part, it 
is not 
unusual 
for non mutually exclusive 
combinations of fetishistic sexual 
interests to occur. Thus, an individual 
may have fetishistic 
disorder associated with an inanimate object 
(e.g., female undergarments) or an exclusive focus 
on an intensely eroticized body part 
(e.g., feet, hair), or his or her fetishistic interest 
may meet 
criteria for various combinations of these specifiers (e.g., socks, shoes, and feet). 


797 


Diagnostic Features 


The paraphilic focus of fetishistic disorder involves the persistent 
and repetitive use of or 
dependence on nonliving objects or a highly specific focus on a (typically nongenital) body part 
as a primary element 
associated with sexual 
arousal 
(Criterion A). A diagnosis of fetishistic 
disorder must 
include clinically significant 
personal 
distress or impairment 
in social, 
occupational, or other important 
areas of functioning (Criterion B). Common fetish objects 



include women s undergarments, men s or women s footwear, rubber articles, leather clothing, 
diapers, or other wearing apparel. Highly eroticized body parts associated with fetishistic 
disorder include feet, toes, and hair. It 
is not 
uncommon for sexualized fetishes to include both 
inanimate objects and body parts (e.g., dirty socks and feet), and for this reason the definition of 
fetishistic disorder now re-incorporates partialism 
(i.e., an exclusive focus on a body part) into 
its boundaries. Partialism, previously considered in DSM-IV-TR 
to be a paraphilia not 
otherwise 
specified, had historically been subsumed in fetishism prior to DSM-III. 


Many individuals who self-identify as fetishist 
practitioners do not 
necessarily report 
clinical 
impairment 
in association with their fetish-associated behaviors. Such individuals could be 
considered as having a fetishistic sexual 
interest 
(i.e., a recurrent 
and intense sexual 
arousal 
from 
either the use of nonliving objects or a highly specific focus on a nongenital 
body part, as 
manifested by fantasies, urges, or behaviors), but 
not 
fetishistic disorder. A diagnosis of 
fetishistic disorder requires concurrent 
fulfillment 
of both the behaviors in Criterion A and the 
clinically significant distress or impairment in functioning noted in Criterion B. 


Associated Features 


Fetishistic disorder can be a multisensory experience, including holding, tasting, rubbing, 
inserting, or smelling the fetish object 
while masturbating, or preferring that 
a sexual 
partner 
wear or utilize a fetish object 
during sexual 
encounters. It 
should be noted that 
many individuals 
with fetishistic sexual 
interests also enjoy sexual 
experiences with their partner(s) without 
using 
their fetish object. However, it 
should also be noted that 
individuals with a fetishistic sexual 
interest 
often find that 
sexual 
experiences that 
involve their fetish object 
are more sexually 
satisfying than sexual 
experience without 
it. And for a minority of people with a fetishistic 
sexual 
interest, their fetish object 
is obligatory to becoming sexually aroused and/or satisfied. 
Some individuals may acquire extensive collections of highly desired fetish objects. 


Development and Course 


Usually paraphilias have an onset 
during puberty, but 
fetishistic sexual 
interests can develop 
prior to adolescence. Once established, fetishistic disorder tends to have a continuous course that 
fluctuates in intensity and frequency of urges or behavior. 


Culture-Related Diagnostic Issues 


Knowledge of and appropriate consideration for normative aspects of sexual 
behavior are 
important 
factors to explore to establish a clinical 
diagnosis of fetishistic disorder and to 
distinguish a clinical diagnosis from a socially acceptable sexual behavior. 


Sex- and Gender-Related Diagnostic Issues 


Fetishistic behaviors have been reported more in men, but 
also occur in women. This gender 
difference is smaller for fetishistic fantasy than for actual fetishistic behavior. In clinical samples, 
fetishistic disorder is nearly exclusively reported in men. 


Functional 
Consequences of Fetishistic Disorder 


Typical 
impairments associated with fetishistic disorder include sexual 
dysfunction during 



romantic reciprocal relationships when the preferred fetish object or body part is 
798 


unavailable during foreplay or coitus. Some individuals with fetishistic disorder may prefer 
solitary sexual 
activity associated with their fetishistic preference(s) even while involved in a 
meaningful reciprocal and affectionate relationship. 


Differential 
Diagnosis 


Transvestic 
disorder. 
The nearest 
diagnostic neighbor of fetishistic disorder is transvestic 
disorder. As noted in the diagnostic criteria, fetishistic disorder is not 
diagnosed when fetish 
objects are limited to articles of clothing exclusively worn during cross-dressing (as in 
transvestic disorder), or when the object 
is genitally stimulating because it 
has been designed for 
that purpose (e.g., a vibrator). 


Sexual 
masochism disorder or other paraphilic 
disorders. 


Fetishistic disorder can co-occur with other 
paraphilic disorders, especially sadomasochistic behavior or interests and transvestic disorder. 
When an individual 
fantasizes about 
or engages in  forced cross-dressing  and is primarily 
sexually aroused by the domination or humiliation associated with such fantasy or repetitive 
activity, and experiences distress or functional 
impairment, the diagnosis of sexual 
masochism 
disorder should be made. 


Fetishism. 
Use of a fetish object 
for sexual 
arousal 
(fetishism) without 
any associated distress or 
psychosocial role impairment or other adverse consequence would not meet criteria for fetishistic 
disorder, as the threshold required by Criterion B 
would not 
be met. For example, an individual 
whose sexual 
partner either shares or can successfully incorporate his interest 
in caressing, 
smelling, or licking feet 
or toes as an important 
element 
of foreplay would not 
be diagnosed with 
fetishistic disorder; 
nor would an individual 
who prefers, and is not 
distressed or impaired by, 
solitary sexual behavior associated with wearing rubber garments or leather boots. 


Comorbidity 


Fetishistic disorder may co-occur with other paraphilic disorders as well 
as hypersexuality. 
Rarely, fetishistic disorder may be associated with neurological conditions. 


Transvestic Disorder 


Diagnostic Criteria 
F65.1 


A. 
Over a 
period 
of 
at 
least 
6 
months, 
recurrent 
and 
intense 
sexual arousal from 
cross-dressing, 
as manifested 
by fantasies, 
urges, 
or behaviors. 
B. 
The 
fantasies, 
sexual urges, 
or behaviors cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
Specify 
if: 



With 
fetishism: 
If 
sexually aroused 
by fabrics, 
materials, 
or garments. 
With 
autogynephilia: 
If 
sexually aroused 
by thoughts or images of 
self 
as a 
woman. 
Specify 
if: 
In 
a 
controlled 
environment: 
This specifier is primarily applicable 
to 
individuals 


living 
in 
institutional or other settings where 
opportunities to 
cross-dress are 
restricted. 
In 
full 
remission: 
There 
has been 
no 
distress or impairment 
in 
social, 


occupational, 
or other areas of 
functioning 
for at 
least 
5 
years while 
in 
an 
uncontrolled 
environment. 


799 


Specifiers 


The presence of fetishism 
decreases the likelihood of gender dysphoria in men with transvestic 
disorder. The presence of autogynephilia increases the likelihood of gender dysphoria in men 
with transvestic disorder. 


Diagnostic Features 


The diagnosis of transvestic disorder does not 
apply to all 
individuals who dress as the opposite 
sex, even those who do so habitually. It 
applies to individuals whose cross-dressing or thoughts 
of cross-dressing are always or often accompanied by sexual 
excitement 
(Criterion A) and who 
are emotionally distressed by this pattern or for whom 
it 
impairs their social 
or interpersonal 
functioning (Criterion B). The cross-dressing may involve only one or two articles of clothing 
(e.g., for men, it 
may pertain only to women s undergarments), or it 
may involve dressing 
completely in the inner and outer garments of the other sex and (in men) may include the use of 
women s wigs and makeup. Sexual 
arousal, in its most 
obvious form 
of penile erection, may co-
occur with cross-dressing in various ways. In younger men, cross-dressing often leads to 
masturbation, following which any women s clothing is removed. Older men often learn to avoid 
masturbating or doing anything to stimulate the penis so that 
the avoidance of ejaculation allows 
them 
to prolong their cross-dressing session. Men and women sometimes complete a cross-
dressing session by having intercourse with their partners, and some have difficulty maintaining 
sufficient 
sexual 
arousal 
for sexual 
activity without 
cross-dressing (or having private fantasies of 
cross-dressing). 


Clinical 
assessment 
of distress or impairment, like clinical 
assessment 
of transvestic sexual 
arousal, is usually dependent 
on the individual s self-report. The pattern of behavior  purging 
and acquisition  often signifies the presence of distress in individuals with transvestic disorder. 
During this behavioral 
pattern, an individual 
(usually a man) who has spent 
a great 
deal 
of 
money on women s clothes and other apparel 
(e.g., shoes, wigs) discards the items (i.e., purges 
them) in an effort 
to overcome urges to cross-dress, and then begins acquiring a woman s 
wardrobe all over again. 



Associated Features 


Transvestic disorder in men is often accompanied by autogynephilia 
(i.e., a man s paraphilic 
tendency to be sexually aroused by the thought 
or image of himself as a woman). Autogynephilic 
fantasies and behaviors may focus on the idea of exhibiting female physiological 
functions (e.g., 
lactation, menstruation), engaging in stereotypically feminine behavior (e.g., knitting), or 
possessing female anatomy (e.g., breasts). 


Prevalence 


The prevalence of transvestic disorder is unknown; 
however, it 
appears to be much more 
prevalent 
in men than in women. Fewer than 3% of Swedish men report 
having ever been 
sexually aroused by dressing in women s attire. The percentage of individuals who have cross-
dressed with sexual 
arousal 
more than once or a few times in their lifetimes would be even 
lower. 


Development and Course 


In men, the first 
signs of transvestic disorder may begin in childhood, in the form 
of strong 
fascination with a particular item 
of women s attire. Prior to puberty, cross-dressing produces 
generalized feelings of pleasurable excitement. With the arrival 
of puberty, dressing in women s 
clothes begins to elicit 
penile erection and, in some cases, leads directly to first 
ejaculation. In 
many cases, cross-dressing elicits less and less sexual 
excitement 
as the individual 
grows older; 
eventually it 
may produce no discernible penile response at 
all. The desire to cross-dress, at 
the 
same time, remains the same or grows even stronger. 


800 


Individuals who report 
such a diminution of sexual 
response typically report 
that 
the sexual 
excitement of cross-dressing has been replaced by feelings of comfort or well-being. 


In some cases, the course of transvestic disorder is continuous, and in others it 
is episodic. It 
is not 
rare for men with transvestic disorder to lose interest 
in cross-dressing when they first 
fall 
in love with a woman and begin a relationship, but 
such abatement 
usually proves temporary. 
When the desire to cross-dress returns, so does the associated distress. 


Some cases of transvestic disorder progress to gender dysphoria. The men in these cases, 
who may be indistinguishable from 
others with transvestic disorder in adolescence or early 
childhood, gradually develop desires to remain in the woman s role for longer periods and to 
feminize their anatomy. The development 
of gender dysphoria is usually accompanied by a (selfreported) 
reduction or elimination of sexual arousal in association with cross-dressing. 


The manifestation of transvestism 
in penile erection and stimulation, like the manifestation of 
other paraphilic as well 
as nonparaphilic sexual 
interests, is most 
intense in adolescence and 
early adulthood. The severity of transvestic disorder is highest 
in adulthood, when the transvestic 
drives are most 
likely to conflict 
with performance in heterosexual 
intercourse and desires to 
marry and start 
a family. Middle-age and older men with a history of transvestism 
are less likely 
to present with transvestic disorder than with gender dysphoria. 


Functional 
Consequences of Transvestic Disorder 



Engaging in transvestic behaviors can interfere with, or detract 
from, heterosexual 
relationships. 
This can be a source of distress to men who wish to maintain conventional 
marriages or romantic 
partnerships with women. 


Differential 
Diagnosis 


Transvestism. 
Individuals with transvestism 
experience recurrent 
and intense sexual 
arousal 
from 
cross-dressing. Unless the fantasies, sexual 
urges, or behaviors involving cross-dressing are 
accompanied by clinically significant 
distress or impairment 
in social, occupational, or other 
important areas of functioning, a diagnosis of transvestic disorder is not warranted. 


Fetishistic 
disorder. 
This disorder may resemble transvestic disorder, in particular, in men with 
fetishism 
who put 
on women s undergarments while masturbating with them. Distinguishing 
transvestic disorder depends on the individual s specific thoughts during such activity (e.g., are 
there any ideas of being a woman, being like a woman, or being dressed as a woman?) and on 
the presence of other fetishes (e.g., soft, silky fabrics, whether these are used for garments or for 
something else). 


Gender dysphoria. 
Individuals with transvestic disorder do not 
report 
an incongruence between 
their experienced gender and their assigned gender or a desire to be of the other gender; 
and they 
typically do not 
have a history of childhood cross-gender behaviors, which would be present 
in 
individuals with gender dysphoria. Individuals with a presentation that 
meets full 
criteria for 
transvestic disorder as well as gender dysphoria should be given both diagnoses. 


Comorbidity 


Transvestic disorder is often found in association with other paraphilias. The most 
frequently co-
occurring paraphilias are fetishistic sexual 
interests or behavior and masochistic sexual 
interests 
or behavior. One particularly dangerous form 
of masochistic sexual 
interests or behavior, 
autoerotic asphyxia, 
is associated with transvestic sexual 
interests or behavior in a substantial 
proportion of fatal cases. 


801 


Other Specified 
Paraphilic Disorder 


F65.89 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
paraphilic disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
paraphilic disorders diagnostic class. 
The 
other specified 
paraphilic disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific paraphilic disorder. 
This is done 
by recording 
 other 
specified 
paraphilic disorder  followed 
by the 
specific reason 
(e.g., 
 zoophilia ). 



Examples of presentations that 
can be specified using the  other specified  designation 
include, but 
are not 
limited to, recurrent 
and intense sexual 
arousal 
involving telephone 
scatologia 
(obscene phone calls), necrophilia 
(corpses), zoophilia 
(animals), coprophilia 
(feces), klismaphilia (enemas), or urophilia 
(urine) that 
has been present 
for at 
least 
6 months 
and causes marked distress or impairment 
in social, occupational, or other important 
areas of 
functioning. Other specified paraphilic disorder can be specified as in remission and/or as 
occurring in a controlled environment. 


Unspecified 
Paraphilic Disorder 


F65.9 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
paraphilic disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any of 
the 
disorders in 
the 
paraphilic disorders diagnostic class. 
The 
unspecified 
paraphilic disorder category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific 
paraphilic disorder, 
and 
includes presentations in 
which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis. 


802 



803 



Other Mental 
Disorders and Additional 
Codes 


This chapter 
provides diagnostic codes for psychiatric presentations that 
are mental 
disorders (i.e., symptoms cause clinically significant 
distress or impairment 
in social, 
occupational, or other important 
areas of functioning) but 
that 
do not 
meet 
diagnostic 
requirements for any of the mental 
disorders in the prior Section II chapters. These codes allow 
for the documentation and coding of these otherwise unclassified mental 
disorders. This chapter 
also includes an additional 
code,  No diagnosis or condition,  for situations in which the 
individual has been evaluated and it is determined that no mental disorder or condition is present. 


The categories 1) other specified mental 
disorder due to another medical 
condition and 2) 
unspecified mental 
disorder due to another medical 
condition are for presentations for which it 
has been determined that 
the psychiatric symptoms (e.g., dissociative symptoms) are a direct 
physiological 
consequence of another medical 
condition but 
do not 
otherwise meet 
diagnostic 
criteria for any of the prior Section II mental 
disorders due to another medical 
condition. For the 
diagnosis of other specified or unspecified mental 
disorder due to another medical 
condition, it 
is 
necessary to code and list 
the medical 
condition first 
(e.g., B20 HIV disease), followed by the 
applicable code for either other specified or unspecified mental 
disorder due to another medical 
condition. 


The categories 1) other specified mental 
disorder and 2) unspecified mental 
disorder are 
residual 
categories used when all 
of the following considerations are met: 
the psychiatric 
presentation is a mental 
disorder (i.e., the symptoms cause clinically significant 
distress or 
impairment 
in social, occupational, or other important 
areas of functioning); 
the presentation 
does not 
meet 
diagnostic criteria for any of the specific mental 
disorders in Section II; 
neither 
does the presentation meet 
the definitional 
requirements of any of the other specified and 
unspecified mental 
disorder categories presented in Section II; 
and no other mental 
disorder 
diagnosis applies. 


As is the case with other specified and unspecified categories throughout 
DSM-5, the other 
specified category is used when the clinician chooses to specify the specific reason that 
the 
presentation does not 
meet 
the criteria for any of the existing categories (e.g., other specified 
mental 
disorder due to complex partial 
seizures, with dissociative symptoms), and the 
unspecified category is used when the clinician chooses not to specify the reason. 


Other Specified 
Mental 
Disorder Due to 
Another Medical 
Condition 


F06.8 
This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
mental 



disorder due 
to 
another medical condition 
that 
cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any specific mental disorder 
attributable 
to 
another medical 


804 


condition. 
The 
other specified 
mental disorder due 
to 
another medical condition 
category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific 
mental disorder attributable 
to 
another medical condition. 
This is done 
by recording 
the 
name 
of 
the 
disorder, 
with 
the 
specific etiological medical condition 
inserted 
in 
place 
of 
 another medical condition,  followed 
by the 
specific symptomatic 
manifestation 
that 
does not 
meet 
the 
criteria 
for any specific mental disorder due 
to 
another medical condition. 
Furthermore, 
the 
diagnostic code 
for the 
specific medical 
condition 
must 
be 
listed 
immediately before 
the 
code 
for the 
other specified 
mental 
disorder due 
to 
another medical condition. 
For example, 
dissociative 
symptoms due 
to 
complex partial seizures would 
be 
coded 
and 
recorded 
as G40.209 
complex 
partial seizures, 
F06.8 
other specified 
mental disorder due 
to 
complex partial 
seizures, 
dissociative 
symptoms. 


An 
example 
of 
a 
presentation 
that 
can 
be 
specified 
using 
the 
 other specified  


designation 
is the 
following: 


Dissociative 
symptoms: 
This includes symptoms occurring, 
for example, 
in 
the 


context 
of 
complex partial seizures. 


805 


Unspecified 
Mental 
Disorder Due to 
Another Medical 
Condition 


F09 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
mental 
disorder due 
to 
another medical condition 
that 
cause 
clinically significant 
distress or 
impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any specific mental disorder due 
to 
another medical condition. 
The 
unspecified 
mental disorder due 
to 
another medical 
condition 
category is used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify 
the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific mental disorder due 
to 
another 
medical condition, 
and 
includes presentations for which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room settings). 
This is done 
by recording 
the 
name 
of 
the 
disorder, 
with 
the 
specific etiological 
medical condition 
inserted 
in 
place 
of 
 another medical condition.  Furthermore, 
the 



diagnostic code 
for the 
specific medical condition 
must 
be 
listed 
immediately before 
the 
code 
for the 
unspecified 
mental disorder due 
to 
another medical condition. 
For 
example, 
dissociative 
symptoms due 
to 
complex partial seizures would 
be 
coded 
and 
recorded 
as G40.209 
complex partial seizures, 
F09 
unspecified 
mental disorder 
due 
to 
complex partial seizures. 


Other Specified 
Mental 
Disorder 


F99 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
mental 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any specific mental disorder. 
The 
other specified 
mental disorder 
category is used 
in 
situations in 
which 
the 
clinician 
chooses to 
communicate 
the 
specific reason 
that 
the 
presentation 
does not 
meet 
the 
criteria 
for any specific 
mental disorder. 
This is done 
by recording 
 other specified 
mental disorder  followed 
by the 
specific reason. 


Unspecified 
Mental 
Disorder 


F99 


This category applies to 
presentations in 
which 
symptoms characteristic of 
a 
mental 
disorder that 
cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning 
predominate 
but 
do 
not 
meet 
the 
full criteria 
for any mental disorder. 
The 
unspecified 
mental disorder category is 
used 
in 
situations in 
which 
the 
clinician 
chooses not 
to 
specify the 
reason 
that 
the 
criteria 
are 
not 
met 
for a 
specific mental disorder, 
and 
includes presentations for 
which 
there 
is insufficient 
information 
to 
make 
a 
more 
specific diagnosis (e.g., 
in 
emergency room settings). 


Additional 
Codes 


Z03.89 No Diagnosis or Condition 


This code applies to situations in which the person has been evaluated and it 
is determined that 
no mental disorder or condition is present. 


806 



807 



Medication-Induced Movement Disorders and 
Other Adverse Effects of Medication 


Medication-induced movement 
disorders are included in Section II because 
of their frequent 
importance in 1) the management 
by medication of mental 
disorders or other 
medical 
conditions and 2) the differential 
diagnosis of mental 
disorders (e.g., anxiety disorder vs. 
medication-induced akathisia; 
malignant 
catatonia [a particularly severe and potentially life-
threatening form 
of catatonia] vs. neuroleptic malignant 
syndrome; 
tardive dyskinesia vs. 
chorea). Although these movement 
disorders are labeled  medication induced,  it 
is often 
difficult to establish the causal relationship between medication exposure and the development of 
the movement 
disorder, especially because some of these movement 
disorders also occur in the 
absence of medication exposure. The conditions and problems listed in this chapter are not 
mental disorders. 


The term 
neuroleptic 
is becoming outdated because it 
highlights the propensity of 
antipsychotic medications to cause abnormal 
movements, and it 
is being replaced with the term 
antipsychotic medications and other dopamine receptor blocking agents 
in many contexts. 
Although newer antipsychotic medications may be less likely to cause some medication-induced 
movement 
disorders, those disorders still 
occur. Antipsychotic medications and other dopamine 
receptor blocking agents include so-called conventional,  typical,  or first-generation 
antipsychotic agents (e.g., chlorpromazine, haloperidol, fluphenazine); 
 atypical  or second-
generation antipsychotic agents (e.g., clozapine, risperidone, olanzapine, quetiapine); 
certain 
dopamine receptor blocking drugs used in the treatment 
of symptoms such as nausea and 
gastroparesis (e.g., prochlorperazine, promethazine, trimethobenzamide, thiethylperazine, 
metoclopramide); and amoxapine, which is indicated for the treatment of depression. 


Medication-Induced Parkinsonism 


G21.11 Antipsychotic Medication  and Other Dopamine Receptor 
Blocking Agent Induced Parkinsonism 


G21.19 Other Medication-Induced Parkinsonism 


Medication-induced parkinsonism 
(MIP), the second most 
common cause of parkinsonism 
after 
Parkinson s disease, is associated with significant 
morbidity, disability, and treatment 
nonadherence, particularly in individuals with psychiatric disorders. Because early recognition is 
important, any new case of parkinsonism 
should prompt 
a thorough medication history, which is 
essential 
for diagnosis of MIP. A temporal 
relationship between medication initiation and onset 
of parkinsonism 
should be evident. A host 
of agents that 
may be prescribed in individuals with 
psychiatric disorders may also induce parkinsonism, but 
MIP 
is most 
often seen upon exposure 



to antipsychotic medications that 
block dopamine D2 
receptors. MIP 
occurs at 
higher rates with 
antipsychotics that 
have higher potency for the dopamine D2 
receptor, such as haloperidol, 
fluphenazine, and risperidone, but there are no 


808 


differences in the clinical 
features of parkinsonism 
between first- and second-generation 
antipsychotics. 


Other medications that 
can cause MIP 
include calcium 
channel 
antagonists (e.g., flunarizine, 
cinnarizine), dopamine depleters (e.g., reserpine, tetrabenazine), antiepileptics (e.g., phenytoin, 
valproate, levetiracetam), antidepressants (e.g., selective serotonin reuptake inhibitors, 
monoamine oxidase inhibitors), lithium, chemotherapeutic drugs (e.g., cystosine arabinoside, 
cyclophosphamide, vincristine, doxorubicin, paclitaxel, etoposide), and immunosuppressants 
(e.g., cyclosporine, tacrolimus). Toxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 
[MPTP], organophosphate pesticides, manganese, methanol, cyanide, carbon monoxide, and 
carbon disulfide) may also cause MIP. 


The time course for development 
of MIP 
varies. Usually, MIP 
develops a few weeks after 
starting or raising the dose of a medication known to cause parkinsonism 
or after reducing an 
antiparkinsonian medication (e.g., an anticholinergic agent) that 
is being used to treat 
or prevent 
medication-induced dystonia or parkinsonian symptoms. However, MIP 
may also develop 
rapidly after starting or raising the dose of a medication or have an insidious onset 
after many 
months of exposure. With antipsychotic medications or other dopamine receptor blocking agents, 
MIP 
typically develops 2 4 weeks after starting the medication and usually by 3 months. Mainly 
with calcium channel blockers, a second peak of symptom onset is reported after about 1 year. 


Reported rates of MIP 
are affected by absence of standard diagnostic criteria, incorrect 
diagnosis or misattribution of MIP 
signs to Lewy body disease (e.g., Parkinson s disease), or a 
psychiatric condition, and overall 
lack of recognition, especially in milder cases. It 
is estimated 
that 
at 
least 
50% of outpatients receiving long-term 
antipsychotic treatment 
with typical 
agents 
develop parkinsonian signs or symptoms at some point in their course of treatment. 


There are no clinical 
characteristics that 
distinguish MIP 
reliably from 
Parkinson s disease. 
Because motor signs and symptoms in Parkinson s disease begin unilaterally and progress 
asymmetrically, the subacute onset 
of bilateral 
parkinsonism 
within weeks of starting an 
antipsychotic or other MIP-causing agent 
is highly suggestive for MIP. Parkinsonian signs are 
often symmetric in MIP, but 
asymmetric patterns are not 
uncommon and should not 
exclude a 
diagnosis of MIP. In addition, the course and presentation of parkinsonism 
should not 
be better 
accounted for by psychiatric phenomena, such as catatonia, negative symptoms of schizophrenia, 
or psychomotor retardation in a major depressive episode; 
other nonparkinsonian medication-
induced movement 
disorders; 
another neurological 
or medical 
condition (e.g., Parkinson s 
disease, Wilson s disease); or antipsychotic-exacerbated Parkinson s disease. 


In MIP, rigidity and bradykinesia are more often present, whereas tremor is somewhat 
less 
common and may be absent. Parkinsonian tremor, also referred to as a  pill-rolling tremor,  is a 
steady, rhythmic oscillatory movement 
(3 6 cycles per second) that 
is apparent 
at 
rest 
and is 
typically slower than other tremors. It may be intermittent, unilateral or bilateral, or dependent on 
limb position (i.e., positional 
tremor). The tremor may involve the limbs, head, jaw, mouth, lip 
( rabbit 
syndrome ), or tongue. As it 
is present 
at 
rest, the tremor can be suppressed, especially 



when the individual 
attempts to perform 
a task with the tremulous limb. Individuals may 
describe the tremor as  shaking  and report that it may worsen with anxiety, stress, or fatigue. 


Parkinsonian rigidity is experienced as an involuntary stiffness and inflexibility of the 
muscles of the limbs, shoulders, neck, or trunk. Rigidity is evaluated by assessing muscle tone, 
or the amount 
of resistance present 
when the examiner moves a limb (and stretches the muscles) 
passively around a joint. In lead-pipe rigidity, increased tone is constant 
throughout 
range of 
motion (in contrast 
to the clasp-knife rigidity spasticity). Cogwheel 
rigidity is thought 
to 
represent 
a tremor superimposed on rigidity. Most 
common in the wrists and elbows, it 
is 
experienced as a rhythmic, ratchet-like resistance (cogwheeling) when the muscles are passively 
moved around a joint. Individuals with parkinsonian rigidity may 


809 


complain of generalized muscle tenderness or stiffness, tightness in their limbs, muscle or 
joint pain, body aching, or lack of coordination. 


Bradykinesia and akinesia are observable states of decreased or absent 
spontaneous motor 
activity, respectively. There is global 
slowing as well 
as slowness in initiating and executing 
movements. Everyday behaviors (e.g., grooming) can be difficult 
to perform 
normally and may 
be reduced. Individuals may complain of listlessness, lack of spontaneity and drive, or fatigue. 
Parkinsonian rigidity and bradykinesia manifest 
as gait 
abnormalities, including decreased stride 
length, arm 
swing, or overall 
spontaneity of walking. Other signs include a hunched posture with 
bent-over neck and stooped shoulders, a staring facial 
expression, and small 
shuffling steps. 
Drooling can arise as a result 
of reduced pharyngeal 
motor activity and swallowing, but 
because 
of anticholinergic properties of these medications, it 
may be less common in antipsychoticinduced 
parkinsonism as compared with other medications that cause MIP. 


MIP 
is associated with increased gait 
dysfunction, falls, and nursing home placement. As 
such, MIP 
is a 
serious iatrogenic movement 
disorder in older individuals that 
warrants 
recognition and early diagnosis. Associated behavioral 
symptoms may include depression and 
worsening of negative signs of schizophrenia. Other parkinsonian signs and symptoms include 
small 
handwriting (micrographia), reduced motor dexterity, hypophonia, decreased gag reflex, 
dysphagia, postural 
instability, reduced facial 
expression and blinking, and seborrhea. When 
parkinsonism 
is associated with severe decreased motor activity, medical 
complications of 
parkinsonism 
include contractures, bedsores, pulmonary emboli, urinary incontinence, aspiration 
pneumonia, weight loss, and hip fractures. 


Consistent 
risk factors are female gender, older age, cognitive impairment, other concurrent 
neurological 
conditions, HIV infection, family history of Parkinson s disease, and severe 
psychiatric disease. MIP 
secondary to antipsychotic use is also reported in children. The risk of 
MIP is reduced if individuals are taking anticholinergic medications. 


Differential 
Diagnosis 


Parkinson s disease and Parkinson s-plus conditions such as multiple system 
atrophy, 
progressive supranuclear palsy, and Wilson s disease are distinguished from 
MIP 
by their other 
signs and symptoms that 
accompany parkinsonism. For example, Parkinson s disease is 
suggested by evidence of three or more cardinal 
features of Parkinson s disease (e.g., resting 



tremor, rigidity, bradykinesia, postural 
instability), hyposmia, sleep disturbances such as rapid 
eye movement 
(REM) sleep behavior disorder, and urinary and other autonomic symptoms 
common to Parkinson s disease. These features are less likely to be present 
in MIP. Individuals 
with primary neurological 
causes of parkinsonism 
are also susceptible to worsening symptoms if 
treated with medications causing MIP. 


Nonparkinsonian tremors tend to be finer (e.g., smaller amplitude) and faster (10 cycles per 
second) and worsen on intention (e.g., when reaching out 
to grab an object). With substance 
withdrawal, there is usually associated hyperreflexia and increased autonomic signs. In cerebellar 
disease, tremor worsens on intention and may be associated with nystagmus, ataxia, or scanning 
speech. Choreiform 
movements associated with tardive dyskinesia lack the steady rhythmicity of 
a parkinsonian tremor. Strokes and other central 
nervous system 
lesions can cause focal 
neurological 
signs or immobility from 
flaccid or spastic paralysis, which is characterized by 
decreased muscle strength and increased tone on passive movement 
that 
gives way with further 
pressure (i.e., clasp-knife rigidity). This contrasts with the lead-pipe rigidity and normal 
muscle 
strength in MIP. 


Diagnostic alternatives to MIP 
are also suggested by a family history of an inherited 
neurological 
condition, rapidly progressive parkinsonism 
not 
accounted for by recent 
psychopharmacological 
changes, or presence of focal 
neurological 
signs (e.g., frontal 
release 
signs, cranial 
nerve abnormalities, a positive Babinski 
sign). Neuroleptic malignant 
syndrome 
involves severe akinesia and rigidity, but 
also characteristic physical 
and laboratory findings 
(e.g., fever, increased creatine phosphokinase). 


810 


Psychomotor slowing, inactivity, and apathy seen in major depressive disorder can be 
indistinguishable from 
the motor slowness or akinesia of MIP, but 
major depressive disorder is 
more likely to include vegetative signs (e.g., early-morning awakening), hopelessness, and 
despair. Negative symptoms of schizophrenia, catatonia associated with schizophrenia, or mood 
disorders with catatonic features may also be difficult 
to distinguish from 
medication-induced 
akinesia. Rigidity may also manifest 
in psychotic disorders, delirium, major neurocognitive 
disorder, anxiety disorders, and functional 
neurological 
symptom disorder (conversion disorder). 
In parkinsonian rigidity, resistance to passive motion is constant 
through the full 
range of 
motion, whereas it 
is inconsistent 
in psychiatric disorders or other neurological 
conditions 
presenting with rigidity. In general, the constellation of associated physical 
signs on examination 
and symptoms associated with the tremor, rigidity, and bradykinesia of parkinsonism 
helps 
distinguish MIP-related rigidity and bradykinesia from 
other primary psychiatric causes of 
rigidity and decreased movement. 


Neuroleptic Malignant 
Syndrome 


G21.0 Neuroleptic Malignant Syndrome 


Individuals with neuroleptic malignant 
syndrome have generally been exposed to a dopamine 
antagonist 
within 72 hours prior to symptom 
development. Hyperthermia (>100.4 F 
or >38.0 C 
on at 
least 
two occasions, measured orally), associated with profuse diaphoresis, is a 



distinguishing feature of neuroleptic malignant 
syndrome, setting it 
apart 
from 
other neurological 
side effects of antipsychotic medications and other dopamine receptor blocking agents. Extreme 
elevations in temperature, reflecting a breakdown in central 
thermoregulation, are more likely to 
support 
the diagnosis of neuroleptic malignant 
syndrome. Generalized rigidity, described as 
 lead pipe  in its most 
severe form 
and usually unresponsive to antiparkinsonian agents, is a 
cardinal 
feature of the disorder and may be associated with other neurological 
symptoms (e.g., 
tremor, sialorrhea, akinesia, dystonia, trismus, myoclonus, dysarthria, dysphagia, 
rhabdomyolysis). Creatine kinase elevation of at 
least 
four times the upper limit 
of normal 
is 
commonly seen. Changes in mental 
status, characterized by delirium 
or altered consciousness 
ranging from 
stupor to coma, are often an early sign of neuroleptic malignant 
syndrome. 
Affected individuals may appear alert 
but 
dazed and unresponsive, consistent 
with catatonic 
stupor. Autonomic activation and instability manifested by tachycardia (rate > 25% above 
baseline), diaphoresis, blood pressure elevation (systolic or diastolic = 25% above baseline) or 
fluctuation (= 20 mmHg diastolic change or =25 mmHg systolic change within 24 hours), urinary 
incontinence, and pallor may be seen at 
any time but 
provide an early clue to the diagnosis. 
Tachypnea (rate > 50% above baseline) is common, and respiratory distress resulting from 
metabolic acidosis, hypermetabolism, chest 
wall 
restriction, aspiration pneumonia, or pulmonary 
emboli can occur and lead to sudden respiratory arrest. 


Although several 
laboratory abnormalities are associated with neuroleptic malignant 
syndrome, no single abnormality is specific to the diagnosis. Individuals with neuroleptic 
malignant 
syndrome may have leukocytosis, metabolic acidosis, hypoxia, decreased serum 
iron 
concentrations, and elevations in serum 
muscle enzymes and catecholamines. Findings from 
cerebrospinal 
fluid analysis and neuroimaging studies are generally normal, whereas 
electroencephalography shows generalized slowing. Autopsy findings in fatal 
cases have been 
nonspecific and variable, depending on complications. 


Evidence from 
database studies suggests incidence rates for neuroleptic malignant 
syndrome 
of 0.01% 0.02% among individuals treated with antipsychotics. A population-based study 
conducted in Hong Kong found an incidence risk of 0.11% in individuals treated with 
antipsychotic medication. 


811 


The temporal 
progression of signs and symptoms provides important 
clues to the diagnosis 
and prognosis of neuroleptic malignant 
syndrome. Alteration in mental 
status and other 
neurological 
signs typically precede systemic signs. The onset 
of symptoms varies from 
hours to 
days after drug initiation. Some cases develop within 24 hours after drug initiation, most 
within 
the first 
week, and virtually all 
cases within 30 days. Once the syndrome is diagnosed and oral 
antipsychotic drugs and other dopamine receptor blocking agents are discontinued, neuroleptic 
malignant 
syndrome is self-limited in most 
cases. The mean recovery time after drug 
discontinuation is 7 10 days, with most 
individuals recovering within 1 week and nearly all 
within 30 days. The duration may be prolonged when long-acting antipsychotic medications are 
implicated. There have been reports of individuals in whom 
residual 
neurological 
signs persisted 
for weeks after the acute hypermetabolic symptoms resolved. Total 
resolution of symptoms can 
be obtained in most 
cases of neuroleptic malignant 
syndrome; 
however, fatality rates of 10%  
20% have been reported when the disorder is not 
recognized. Although many individuals do not 



experience a recurrence of neuroleptic malignant 
syndrome when rechallenged with 
antipsychotic medication, some do, especially when antipsychotic medications are reinstituted 
soon after an episode. 


Neuroleptic malignant 
syndrome is a potential 
risk in any individual 
after administration of 
an antipsychotic medication or other dopamine receptor blocking agent. It 
is not 
specific to any 
neuropsychiatric diagnosis and may occur in persons without 
a diagnosable mental 
disorder who 
receive dopamine antagonists. Clinical, systemic, and metabolic factors associated with a 
heightened risk of neuroleptic malignant 
syndrome include agitation, exhaustion, dehydration, 
and iron deficiency. A prior episode associated with antipsychotic medication and other 
dopamine receptor blocking agents has been described in 15% 20% of index cases, suggesting 
underlying vulnerability in some individuals; 
however, genetic findings based on 
neurotransmitter receptor polymorphisms have not been replicated consistently. 


Nearly all 
antipsychotic medication and other dopamine receptor blocking agents have been 
associated with neuroleptic malignant 
syndrome, although high-potency antipsychotics pose a 
greater risk compared with low-potency agents and atypical 
antipsychotics. Partial 
or milder 
forms may be associated with newer antipsychotics, but 
neuroleptic malignant 
syndrome varies 
in severity even with older drugs. Dopamine receptor blocking agents used in medical 
settings 
(e.g., metoclopramide, prochlorperazine) have also been implicated. Parenteral 
administration 
routes, rapid titration rates, and higher total 
drug dosages have been associated with increased 
risk; 
however, neuroleptic malignant 
syndrome usually occurs within the therapeutic dosage 
range of antipsychotic medications and other dopamine receptor blocking agents. 


Differential 
Diagnosis 


Neuroleptic malignant 
syndrome should be distinguished from 
other serious neurological 
or 
medical 
conditions, including central 
nervous system 
infections, inflammatory or autoimmune 
conditions, status epilepticus, subcortical 
structural 
lesions, and systemic conditions (e.g., 
pheochromocytoma, thyrotoxicosis, tetanus, heat stroke). 


Neuroleptic malignant 
syndrome also should be distinguished from 
similar syndromes 
resulting from 
the use of other substances or medications, such as serotonin syndrome; 
parkinsonian hyperthermia syndrome following abrupt 
discontinuation of dopamine agonists; 
alcohol 
or sedative withdrawal; 
malignant 
hyperthermia occurring during anesthesia; 
hyperthermia associated with misuse of stimulants and hallucinogens; 
and atropine poisoning 
from anticholinergics. 


In rare instances, individuals with schizophrenia or a mood disorder may present 
with 
malignant 
catatonia, which may be indistinguishable from 
neuroleptic malignant 
syndrome. 
Some investigators consider neuroleptic malignant 
syndrome to be a drug-induced form 
of 
malignant catatonia. 


812 


Medication-Induced Acute Dystonia 


G24.02 Medication-Induced Acute Dystonia 


The essential 
feature of medication-induced acute dystonia is sustained abnormal 
muscle 



contractions (increased muscle tone) and postures that 
develop in association with use of a 


medication known to cause acute dystonia. Any medication that 
blocks dopamine D2-like 
receptors can induce an acute dystonic reaction (ADR). Most 
commonly, ADRs occur after 
exposure to antipsychotics and antiemetic and promotility agents. A variety of other medication 
classes are also reported to have induced ADRs, including selective serotonin reuptake 
inhibitors, cholinesterase inhibitors, opioids, and methylphenidate. 


Dystonic reactions vary greatly in severity and location and can be focal, segmented, or 
generalized. They most 
often affect 
head and neck muscles, but 
can extend to upper and lower 
limbs or trunk. A common presentation is acute oro-mandibular (jaw) dystonia involving the 
tongue and mouth with tongue protrusion, or gaping or grimacing postures that 
can impair 
speech (dysarthria) and swallowing (dysphagia) and may evolve into frank trismus (lockjaw). 
Involvement 
of ocular muscles (oculogyric crisis) manifests as involuntary forced and sustained 
conjugate deviations of eyes upward, downward, or sideways that 
can last 
minutes to hours. 
Blepharospasm 
can also occur. Cervical 
(neck) dystonia presents as abnormal 
forward, 
backward, lateral, or twisting positions of the head and neck in relation to the body (e.g., 
antecollis, retrocollis, laterocollis, and torticollis). Focal 
limb dystonia, generally more distal 
than proximal, Pisa syndrome (lateral 
bending of the trunk with a tendency to lean to one side), 
and back arching that 
may evolve into opisthotonos (backward arching of head, neck, and spine) 
can also occur. Acute laryngeal 
dystonia is life-threatening, causing airway obstruction, and 
manifests as a  clutching of the throat,  stridor, dysphonia, dysphagia, dyspnea, and respiratory 
distress from the medication effects on vocal cords and laryngeal muscles. 


At 
least 
50% of individuals develop ADR 
signs or symptoms within 24 48 hours of starting 
or rapidly raising the dose of antipsychotic medication or other dopamine receptor blocking 
agent 
or of reducing a medication being used to treat 
or prevent 
acute extrapyramidal 
symptoms 
(e.g., anticholinergic agents). Approximately 90% of affected individuals have onset 
of ADRs 
within 5 days. The symptoms must 
not 
be better accounted for by a mental 
disorder (e.g., 
catatonia) and must 
not 
be due to a primary neurological 
or other medical 
condition, or a tardive 
medication-induced movement disorder. 


Fear and anxiety often accompany ADRs given their intense nature, inability of the 
individual 
to control 
or stop the movements, and, when present, difficulty breathing, speaking, or 
swallowing. Some individuals experience pain or cramps in affected muscles. Individuals who 
are unaware of the possibility of developing a medication-induced dystonia can be especially 
distressed, increasing the likelihood of subsequent 
medication nonadherence. Thought 
disorder, 
delusions, or mannerisms in an individual 
with psychosis may cause the affected individual 
or 
others to mistakenly regard his or her dystonic symptoms as a feature of the psychiatric 
condition, which could lead to increased doses of the causative medication. The risk of 
developing ADRs is greatest 
in children and in adults younger than age 40 with psychosis, with a 
greater incidence in males than females in both children and adults. Other risk factors for 
developing ADRs include prior dystonic reactions to antipsychotic medications or other 
dopamine receptor blocking agents and use of high-potency typical antipsychotic medications. 


Differential 
Diagnosis 


It 
is important 
to distinguish between medication-induced ADRs and other causes of dystonia, 
especially in individuals being treated with antipsychotic or other dopamine receptor blocking 



medications. A primary neurological or other medical condition is evident 


813 


based on the time course and evolution of the dystonic phenomena (e.g., dystonia precedes 
exposure to the antipsychotic medication or progresses in the absence of change in medication) 
and, possibly, other evidence of focal 
neurological 
signs. Idiopathic focal 
or segmental 
dystonias 
usually persist 
for several 
days or weeks independent 
of medication. A family history of dystonia 
may also be present. Tardive dystonia secondary to medication exposure, including antipsychotic 
medication or other dopamine receptor blocking agents, does not 
have acute onset 
and may 
become evident 
when the dose of an antipsychotic medication is lowered. Other neurological 
conditions (e.g., epileptic seizures, viral 
and bacterial 
infections, trauma, space-occupying 
lesions in the peripheral 
or central 
nervous system) and endocrinopathies (e.g., 
hypoparathyroidism) can also produce symptoms (e.g., tetany) that 
resemble a medication-
induced acute dystonia. Other diagnoses that 
mimic an acute medication-induced dystonia 
include anaphylaxis, tardive laryngeal 
dystonia, and respiratory dyskinesia. Neuroleptic 
malignant 
syndrome can produce dystonia but 
differs in that 
it 
is also accompanied by fever and 
generalized rigidity. 


Catatonia associated with a mood disorder or schizophrenia can be distinguished by the 
temporal 
relationship between the symptoms and the exposure to antipsychotic treatment 
(e.g., 
dystonia preceding exposure to antipsychotic medication) and response to pharmacological 
intervention (e.g., no improvement 
after lowering of dose of the antipsychotic medication or in 
response to anticholinergic administration). Furthermore, individuals with medication-induced 
acute dystonia are generally distressed about 
the dystonic reaction and usually seek intervention. 
In contrast, individuals with the retarded type of catatonia are typically mute and withdrawn and 
do not express subjective distress about their condition. 


Medication-Induced Acute Akathisia 


G25.71 Medication-Induced Acute Akathisia 


The essential 
features of medication-induced acute akathisia are subjective complaints of 
restlessness and at 
least 
one of the following observed movements: 
fidgety movements or 
swinging of the legs while seated, rocking from 
foot 
to foot 
or  walking on the spot  while 
standing, pacing to relieve the restlessness, or an inability to sit 
or stand still 
for at 
least 
several 
minutes. Individuals experiencing the most 
severe form 
of medication-induced acute akathisia 
may be unable to maintain any position for more than a few seconds. The subjective complaints 
include a sense of inner restlessness, most 
often in the legs; 
a compulsion to move one s legs; 
distress if one is asked not 
to move one s legs; 
and dysphoria and anxiety. The symptoms 
typically occur within 4 weeks of initiating or increasing the dose of a medication that 
can cause 
akathisia, which includes antipsychotic medications and other dopamine receptor blocking 
agents, tricyclic antidepressants, selective serotonin reuptake inhibitors, dopamine agonists, and 
calcium 
channel 
blockers, and can occasionally follow the reduction of medication used to treat 
or prevent 
acute extrapyramidal 
symptoms (e.g., anticholinergic agents). The symptoms are not 
better explained by a mental 
disorder (e.g., schizophrenia, substance withdrawal, agitation from 
a 



major depressive or manic episode, hyperactivity in attention-deficit/hyperactivity disorder) and 
are not 
due to a neurological 
or other medical 
condition (e.g., Parkinson s disease, iron-
deficiency anemia). 


The subjective distress resulting from 
akathisia is significant 
and can lead to noncompliance 
with antipsychotic or antidepressant 
treatment. Akathisia may be associated with dysphoria, 
irritability, aggression, or suicide attempts. Worsening of psychotic symptoms or behavioral 
dyscontrol 
may lead to an increase in medication dose, which may exacerbate the problem. 
Akathisia can develop very rapidly after initiating or increasing the causative medication. The 
development of akathisia appears to be dose dependent and to be more frequently associated with 
particular high-potency antipsychotic medications or drugs with higher affinity for central 
dopamine receptors. Acute akathisia tends to persist for 


814 


as long as the causative medication is continued, although the intensity may fluctuate over 
time. The reported prevalence of akathisia among individuals receiving antipsychotic medication 
or other dopamine receptor blocking agents has varied widely (20% 75%). Variations in 
reported prevalence may be attributable to a lack of consistency in the definition, antipsychotic 
prescribing practices, study design, and the demographics of the population being studied. 


Differential 
Diagnosis 


Medication-induced acute akathisia may be clinically indistinguishable from 
syndromes of 
restlessness due to certain neurological 
or other medical 
conditions, and to agitation presenting 
as part 
of a mental 
disorder (e.g., a manic episode). The akathisia of Parkinson s disease and 
iron-deficiency anemia is phenomenologically similar to medication-induced acute akathisia. 
The frequently abrupt 
appearance of restlessness soon after initiation or increase in medication 
usually distinguishes medication-induced acute akathisia. 


Serotonin-specific reuptake inhibitor antidepressant 
medications may produce akathisia that 
appears to be identical 
in phenomenology and treatment 
response to akathisia induced by 
antipsychotic medication or other dopamine receptor blocking agents. Tardive dyskinesia also 
often has a component 
of generalized restlessness that 
may coexist 
with akathisia in an 
individual 
receiving antipsychotic medications or other dopamine blocking agents. Antipsychotic 
medication and other dopamine blocking agent induced acute akathisia is differentiated from 
antipsychotic medication and other dopamine blocking agent induced tardive dyskinesia by the 
nature of the movements and their relationship to the initiation of medication. The time course of 
symptomatic presentation relative to medication dose changes may aid in this distinction. An 
increase in antipsychotic medication will 
often exacerbate akathisia, whereas it 
often temporarily 
relieves the symptoms of tardive dyskinesia. 


Medication-induced acute akathisia should be distinguished from 
symptoms that 
are better 
accounted for by a mental 
disorder. Individuals with depressive episodes, manic episodes, 
generalized anxiety disorder, schizophrenia spectrum 
and other psychotic disorders, attentiondeficit/
hyperactivity disorder, major neurocognitive disorder, delirium, substance intoxication 
(e.g., with cocaine), or substance withdrawal 
(e.g., from 
an opioid) may also display agitation 
that 
is difficult 
to distinguish from 
akathisia. Some of these individuals are able to differentiate 



akathisia from 
the anxiety, restlessness, and agitation characteristic of a mental 
disorder by their 
experience of akathisia as being different 
from 
previously experienced feelings. Other evidence 
that 
restlessness or agitation may be better accounted for by a mental 
disorder includes the onset 
of agitation prior to exposure to the causative medication, absence of increasing restlessness with 
increasing doses of the causative medication, and absence of relief with pharmacological 
interventions (e.g., no improvement 
after decreasing the dose of the causative medication or 
treatment with another medication intended to treat the akathisia). 


Tardive Dyskinesia 


G24.01 Tardive Dyskinesia 


The essential 
features of tardive dyskinesia are abnormal, involuntary movements of the tongue, 
jaw, trunk, or extremities that 
develop in association with the use of medications that 
block 
postsynaptic dopamine receptors, such as first- and second-generation antipsychotic medications 
and other medications such as metoclopramide for gastrointestinal 
disorders. The movements are 
present 
over a period of at 
least 
4 weeks and may be choreiform 
(rapid, jerky, nonrepetitive), 
athetoid (slow, sinuous, continual), or semirhythmic (e.g., stereotypies) in nature; 
however, the 
movements are distinctly different from the rhythmic 


815 


(3-6 Hz) tremors commonly seen in medication-induced parkinsonism. Signs or symptoms of 
tardive dyskinesia develop during exposure to the antipsychotic medication or other dopamine 
blocking agent, or within 4 weeks of withdrawal 
from 
an oral 
agent 
(or within 8 weeks of 
withdrawal 
from 
a long-acting injectable agent). There must 
be a history of the use of the 
offending agent 
for at 
least 
3 months (or 1 month in individuals age 60 years or older). Although 
a large number of epidemiological 
studies have established the etiological 
relationship between 
dopamine blocking drug use and tardive dyskinesia, any dyskinesia in an individual 
who is 
receiving antipsychotic medication is not necessarily tardive dyskinesia. 


Abnormal 
orofacial 
movements are the most 
obvious manifestations of tardive dyskinesia 
and have been observed in most 
individuals afflicted with tardive dyskinesia; 
however, 
approximately one-half can have limb involvement, and up to one-quarter can have axial 
dyskinesia of the neck, shoulders, or trunk. Involvement 
of other muscle groups (e.g., 
pharyngeal, diaphragm, abdominal) may occur but 
is uncommon, especially in the absence of 
dyskinesia of the orofacial 
region, limbs, or trunk. Limb or truncal 
dyskinesia without 
orofacial 
involvement 
may be more common in younger individuals, whereas orofacial 
dyskinesias are 
typical in older individuals. 


The symptoms of tardive dyskinesia tend to be worsened by stimulants, antipsychotic 
medication withdrawal, and anticholinergic medications (such as benztropine, commonly used to 
manage medication-induced parkinsonism) and may be transiently worsened by emotional 
arousal, stress, and distraction during voluntary movements in unaffected parts of the body. The 
abnormal 
movements of dyskinesia are transiently reduced by relaxation and by voluntary 
movements in affected parts of the body. They are generally absent during sleep. Dyskinesia may 
be suppressed, at least temporarily, by increased doses of antipsychotic medication. 



The overall 
prevalence of tardive dyskinesia in individuals who have received long-term 
antipsychotic medication treatment 
ranges from 
20% to 30%. The overall 
incidence among 
younger individuals ranges from 
3% to 5% per year. Middle-age and elderly individuals appear 
to develop tardive dyskinesia more often, with prevalence figures reported up to 50% and an 
incidence of 25% 30% after an average of 1 year s cumulative exposure to antipsychotic 
medication. Prevalence also varies depending on setting, with tardive dyskinesia tending to be 
more common among chronically institutionalized individuals. Variations in reported prevalence 
may be attributable to a lack of consistency in the definition of tardive dyskinesia, antipsychotic 
prescribing practices, study design, and the demographics of the population being studied. 


There is no obvious gender difference in the susceptibility to tardive dyskinesia, although the 
risk may be somewhat 
greater in postmenopausal 
women. Greater cumulative amounts of 
antipsychotic medications and early development 
of acute extrapyramidal 
side effects (such as 
medication-induced parkinsonism) are two of the most 
consistent 
risk factors for tardive 
dyskinesia. Mood disorders (especially major depressive disorder), neurological 
conditions, and 
alcohol 
use disorder have also been found to be risk factors in some groups of individuals. 
Second-generation antipsychotics are associated with a somewhat 
lower incidence of tardive 
dyskinesia compared with first-generation antipsychotics, but 
the difference is not 
as large as 
once thought, especially when the dose of the first-generation antipsychotic is taken into account; 
the most important risk factors are age and cumulative exposure. 


Onset 
of tardive dyskinesia may occur at 
any age and is almost 
always insidious. The signs 
are typically minimal 
to mild at 
onset 
and escape notice except 
by a keen observer. In many 
cases, tardive dyskinesia is objectively mild but, although it 
has been thought 
of as a cosmetic 
problem, can be associated with significant 
distress and social 
avoidance. In severe cases, it 
may 
be associated with medical 
complications (e.g., ulcers in cheeks and tongue; 
loss of teeth; 
macroglossia; 
difficulty in walking, swallowing, or breathing; 
muffled speech; 
weight 
loss; 
depression; suicidal ideation). In older individuals there is a greater 


816 


likelihood that 
tardive dyskinesia may become more severe or more generalized with 
continued antipsychotic medication use. When antipsychotic medications are discontinued, some 
individuals experience symptom 
improvement 
over time; 
however, for others tardive dyskinesia 
can be enduring. 


Differential 
Diagnosis 


It 
is imperative to distinguish medication-induced parkinsonism 
from 
tardive dyskinesia because 
the treatments commonly used to manage medication-induced parkinsonism 
(i.e., anticholinergic 
medications) may worsen the abnormal 
motor movements associated with tardive dyskinesia. 
Moreover, treatments used to manage tardive dyskinesia (i.e., VMAT2 inhibitors) may worsen 
the symptoms of medication-induced parkinsonism. 


Dyskinesia that 
emerges during withdrawal 
from 
an antipsychotic medication or other 
dopamine receptor blocking agent 
may remit 
with continued withdrawal 
from 
the medication. If 
the dyskinesia persists for at 
least 
4 weeks, a diagnosis of tardive dyskinesia may be warranted. 
Tardive dyskinesia must 
be distinguished from 
other causes of orofacial 
and body dyskinesia. 



These conditions include Huntington s disease, Wilson s disease, Sydenham s (rheumatic) 
chorea, systemic lupus erythematosus, thyrotoxicosis, heavy metal 
poisoning, ill-fitting dentures, 
dyskinesia due to other medications such as L-dopa or bromocriptine, and spontaneous 
dyskinesias. Factors that 
may be helpful 
in making the distinction are evidence that 
the 
symptoms preceded the exposure to the antipsychotic medication or other dopamine receptor 
blocking agent 
or that 
other focal 
neurological 
signs are present. It 
should be noted that 
other 
movement 
disorders may coexist 
with tardive dyskinesia. Because spontaneous dyskinesia can 
occur in more than 5% of individuals and is also more common in elderly persons, it 
may be 
difficult 
to prove that 
antipsychotic medications produced tardive dyskinesia in a given 
individual. Tardive dyskinesia must 
be distinguished from 
symptoms that 
are due to a 
medication-induced acute movement 
disorder (e.g., medication-induced parkinsonism, acute 
dystonia, acute akathisia). Acute dystonia and acute akathisia can develop quickly within hours 
to days, and medication-induced parkinsonism 
develops within weeks of initiating or increasing 
the dose of an antipsychotic medication or other dopamine receptor blocking agent 
(or reducing 
the dose of a medication used to treat 
the acute extrapyramidal 
symptoms). Tardive dyskinesia, 
on the other hand, generally develops after more prolonged exposure to antipsychotic medication 
(months to years) and can appear after the withdrawal 
of antipsychotic medication; 
the minimum 
exposure history required for the diagnosis of tardive dyskinesia is antipsychotic medication use 
for at least 3 months (or 1 month in middle-age and elderly individuals). 


Tardive Dystonia Tardive Akathisia 


G24.09 Tardive Dystonia 
G25.71 Tardive Akathisia 


This category is for tardive syndromes involving other types of movement 
problems, such as 
dystonia or akathisia, which are distinguished by their late emergence in the course of treatment 
and their potential 
persistence for months to years, even in the face of discontinuation of an 
antipsychotic medication or other dopamine receptor blocking agent or dosage reduction. 


817 


Medication-Induced Postural Tremor 


G25.1 Medication-Induced Postural 
Tremor 


The essential 
feature of this condition is a fine tremor occurring during attempts to maintain a 
posture, which develops in association with the use of medication. Medications with which such 
a tremor may be associated include lithium,  -adrenergic medications (e.g., isoproterenol), 
stimulants (e.g., amphetamine), dopaminergic medications, anticonvulsant 
medications (e.g., 
valproic acid), antidepressant 
medications, and methylxanthines (e.g., caffeine, theophylline). 
The tremor is a regular, rhythmic oscillation of the limbs (most 
commonly hands and fingers), 
head, mouth, or tongue, most 
commonly with a frequency of between 8 and 12 cycles per 
second. It 
is most 
easily observed when the affected body part 
is held in a sustained posture (e.g., 
hands outstretched, mouth held open). The tremor may worsen in severity when the affected 



body part 
is moved intentionally (kinetic or action tremor). When an individual 
describes a 
tremor that 
is consistent 
with postural 
tremor but 
the clinician does not 
directly observe the 
tremor, it 
may be helpful 
to try to re-create the situation in which the tremor occurred (e.g., 
drinking from a cup and saucer). 


Most 
available information concerns lithium-induced tremor. Lithium 
tremor is a common, 
usually benign, and well-tolerated side effect 
of therapeutic doses. However, it 
may cause social 
embarrassment, occupational 
difficulties, and noncompliance in some individuals. As serum 
lithium 
levels approach toxic levels, the tremor may become coarser and be accompanied by 
muscle twitching, fasciculations, or ataxia. Nontoxic lithium 
tremor may improve spontaneously 
over time. A variety of factors may increase the risk of lithium 
tremor (e.g., increasing age, high 
serum 
lithium 
levels, concurrent 
antidepressant 
or antipsychotic medication or another dopamine 
receptor blocking agent, excessive caffeine intake, personal 
or family history of tremor, presence 
of alcohol 
use disorder, and associated anxiety). The frequency of complaints about 
tremor 
appears to decrease with duration of lithium 
treatment. Factors that 
may exacerbate the tremor 
include anxiety, stress, fatigue, hypoglycemia, thyrotoxicosis, pheochromocytoma, hypothermia, 
and alcohol withdrawal. Tremor can also be an early feature of serotonin syndrome. 


Differential 
Diagnosis 


Medication-induced postural 
tremor should be distinguished from 
a preexisting tremor that 
is not 
caused by the effects of a medication. Factors that 
help to establish that 
the tremor was 
preexisting include its temporal 
relationship to the initiation of medication, lack of correlation 
with serum 
levels of the medication, and persistence after the medication is discontinued. If a 
preexisting, nonpharmacologically induced tremor is present 
(e.g., essential 
tremor) that 
worsens 
with medication, such a tremor would not 
be considered to be medication-induced postural 
tremor. The factors described above that 
may contribute to the severity of a medication-induced 
postural 
tremor (e.g., anxiety, stress, fatigue, hypoglycemia, thyrotoxicosis, pheochromocytoma, 
hypothermia, alcohol withdrawal) may also be a cause of tremor independent of the medication. 


Medication-induced postural 
tremor is not 
diagnosed if the tremor is better accounted for by 
medication-induced parkinsonism. A medication-induced postural 
tremor is usually absent 
at 
rest 
and intensifies when the affected part 
is brought 
into action or held in a sustained position. In 
contrast, the tremor related to medication-induced parkinsonism 
is usually lower in frequency 
(3 6 Hz), worse at 
rest, and suppressed during intentional 
movement 
and usually occurs in 
association with other symptoms of medication-induced parkinsonism (e.g., akinesia, rigidity). 


818 


Other Medication-Induced Movement 
Disorder 


G25.79 Other Medication-Induced Movement Disorder 


This category is for medication-induced movement 
disorders not 
captured by any of the specific 
disorders listed earlier. Examples include 1) presentations resembling neuroleptic malignant 
syndrome that 
are associated with medications other than antipsychotic medications and other 
dopamine receptor blocking agents and 2) other medication-induced tardive conditions. 



Antidepressant 
Discontinuation Syndrome 


T43.205A Initial 
encounter 
T43.205D Subsequent encounter 
T43.205S 
Sequelae 


Discontinuation symptoms may occur following treatment 
with all 
types of antidepressants. The 
incidence of this syndrome depends on the dosage and half-life of the medication being taken, as 
well 
as the rate at 
which the medication is tapered. Short 
half-life medications that 
are abruptly 
discontinued (or when the dose is significantly reduced) rather than tapered gradually may pose 
the greatest 
risk. The short-acting antidepressants paroxetine and venlafaxine are the agents most 
commonly associated with discontinuation symptoms. Antidepressant 
discontinuation syndrome 
may occur in the context 
of intermittent 
non-adherence to treatment 
and therefore may be 
irregularly present 
in some individuals who have not 
actually stopped taking the medication. 
This is especially true for very short 
half-life medications (e.g., venlafaxine). By contrast, long 
half-life medications like fluoxetine seldom produce significant discontinuation effects. 


Unlike withdrawal 
syndromes associated with opioids, alcohol, and other substances, 
antidepressant 
discontinuation syndrome has no pathognomonic symptoms. Instead, the 
symptoms tend to be vague and variable. Symptoms typically begin 2 4 days after the last 
dose 
of the antidepressant. For selective serotonin reuptake inhibitors, symptoms such as dizziness, 
tinnitus,  electric shock  like sensations, insomnia, and acute anxiety are described. The 
antidepressant 
use before discontinuation must 
not 
have incurred hypomania or mixed state (i.e., 
there should be confidence that 
the discontinuation syndrome is not 
the result 
of fluctuations in 
mood stability associated with the previous treatment). For the tricyclic antidepressants, sudden 
discontinuation has been associated with gastrointestinal 
symptoms (cramping reflecting 
cholinergic overactivity after stopping an anticholinergic tricyclic antidepressant) as well 
as 
rebound hypomania. 


The antidepressant 
discontinuation syndrome is based solely on pharmacological 
factors and 
is not 
related to the reinforcing effects of an antidepressant. Unlike the discontinuation of 
substances with reinforcing effects like opioids, drug craving does not 
occur. Also, when a 
stimulant 
is used to augment 
an antidepressant, abrupt 
cessation may result 
in stimulant 
withdrawal 
symptoms (see  Stimulant 
Withdrawal  in the chapter  Substance-Related and 
Addictive Disorders ) rather than the antidepressant discontinuation syndrome described here. 


The prevalence of antidepressant discontinuation syndrome is unknown but is thought to vary 
according to any of the following factors: 
the dosage before discontinuation, the half-life (i.e., 
occurring more commonly with short 
half-life medications) and receptor-binding affinity of the 
medication (e.g., more likely to occur with serotonin reuptake inhibitors), and possibly the 
individual s genetically influenced rate of metabolism for this 


819 


medication. Therefore, discontinuation reactions occur more frequently with short 
half-life 
medications, but 
may also be influenced by rapid or ultrarapid metabolizer status of cytochrome 
enzymes that metabolize the antidepressant. 



Because longitudinal 
studies are lacking, little is known about 
the clinical 
course of 
antidepressant 
discontinuation syndrome. Symptoms appear to abate over time with very gradual 
dosage reductions. Symptoms are usually short-lived, lasting no more than 2 weeks, and are 
seldom present more than 3 weeks after discontinuation. 


Differential 
Diagnosis 


The differential 
diagnosis of antidepressant 
discontinuation syndrome includes a relapse of the 
disorder for which the medication was prescribed (e.g., depression or panic disorder), somatic 
symptom 
disorder, bipolar I or bipolar II disorder with mixed features, substance use disorders, 
migraine, or cerebrovascular accident. Discontinuation symptoms often resemble symptoms of a 
persistent 
anxiety disorder or a return of somatic symptoms of depression for which the 
medication was initially given. It 
is important 
not 
to confuse discontinuation syndrome with a 
relapse of the original 
depressive or anxiety disorder for which the medication was being 
prescribed. Antidepressant 
discontinuation syndrome differs from 
substance withdrawal 
in that 
antidepressants themselves have no reinforcing or euphoric effects. Individuals typically do not 
escalate the dose of medications on their own, and they generally do not 
engage in drug-seeking 
behavior to obtain additional medication. Criteria for a substance use disorder are not met. 


Other Adverse Effect 
of 
Medication 


T50.905A Initial 
encounter 
T50.905D Subsequent encounter 
T50.905S 
Sequelae 


This category is available for optional 
use by clinicians to code side effects of medication (other 
than movement 
symptoms) when these adverse effects become a main focus of clinical 
attention. 
Examples include severe hypotension, cardiac arrhythmias, and priapism. 


820 



821 



Other Conditions That May Be a Focus of 
Clinical 
Attention 


This chapter 
includes conditions and psychosocial 
or environmental 
problems that 
may be 
a focus of clinical 
attention or otherwise affect 
the diagnosis, course, prognosis, or treatment 
of 
an individual s mental 
disorder. These conditions are presented with their corresponding codes 
from 
ICD-10-CM (usually Z 
codes). A condition or problem 
in this chapter may be coded 1) if it 
is a reason for the current 
visit; 
2) if it 
helps to explain the need for a test, procedure, or 
treatment; 
3) if it 
plays a role in the initiation or exacerbation of a mental 
disorder; 
or 4) if it 
constitutes a problem that should be considered in the overall management plan. 


The conditions and problems listed in this chapter are not 
mental 
disorders. Their inclusion in 
DSM-5-TR 
is meant 
to draw attention to the scope of additional 
issues that 
may be encountered 
in routine clinical 
practice and to provide a systematic listing that 
may be useful 
to clinicians in 
documenting these issues. 


For quick reference to all 
codes in this section, see the DSM-5-TR 
Classification. Conditions 
and problems that may be a focus of clinical attention are listed in the subsequent text as follows: 


1. Suicidal 
behavior 
(potentially self-injurious behavior with at 
least 
some intent 
to die) and 
nonsuicidal 
self-injury 
(intentional 
self-inflicted damage to the body in the absence of 
suicidal intent). 
2. Abuse and 
neglect 
(e.g., child and adult 
maltreatment 
and neglect 
problems, including 
physical abuse, sexual abuse, neglect, and psychological abuse). 
3. Relational 
problems 
(e.g., parent-child relational 
problem, sibling relational 
problem, 
relationship distress with spouse or intimate partner, disruption by separation or divorce). 
4. Educational 
problems 
(e.g., illiteracy or low-level 
literacy, schooling unavailable or 
unattainable, failed school examinations, underachievement in school). 
5. Occupational 
problems 
(e.g., unemployment, change of job, threat 
of job loss, stressful 
work schedule, discord with boss and workmates). 
6. Housing problems 
(e.g., homelessness; 
inadequate housing; 
discord with neighbor, lodger, 
or landlord). 
7. Economic problems 
(e.g., lack of adequate food or safe drinking water, extreme poverty, 
low income). 
8. Problems related 
to the social 
environment 
(e.g., problem 
related to living alone, 
acculturation difficulty, social exclusion or rejection). 
9. Problems related 
to interaction 
with 
the legal 
system 
(e.g., conviction in criminal 
proceedings, imprisonment 
or other incarceration, problems related to release from 
prison, 
problems related to other legal circumstances). 
10. Problems related 
to other psychosocial, personal, and 
environmental 
circumstances 
(e.g., problems related to unwanted pregnancy, victim of crime, victim of terrorism). 

11. Problems related 
to access to medical 
and 
other health 
care 
(e.g., unavailability or 
inaccessibility of health care facilities). 
12. Circumstances of personal 
history 
(e.g., personal 
history of psychological 
trauma, military 
deployment). 
822 


13. Other health 
service encounters for counseling and 
medical 
advice 
(e.g., sex counseling, 
other counseling or consultation). 
14. Additional 
conditions or problems that may be a focus of clinical 
attention 
(e.g., 
wandering associated with a mental 
disorder, uncomplicated bereavement, phase of life 
problem). 
Suicidal Behavior and Nonsuicidal Self-Injury 


Coding Note for ICD-10-CM Suicidal Behavior 


For T codes only, the 6th character should be coded as follows: 
A (initial 
encounter) Use while the individual 
is receiving active treatment 
for the 


condition (e.g., emergency department 
encounter, evaluation and treatment 
by a new 


clinician); or 


D (subsequent encounter) Use for encounters after the individual 
has received active 


treatment 
for the condition and when he or she is receiving routine care for the condition 


during the healing or recovery phase (e.g., medication adjustment, other aftercare and 


follow-up visits). 


Suicidal 
Behavior 


This category may be used for individuals who have engaged in potentially self-injurious 
behavior with at 
least 
some intent 
to die as a result 
of the act. Evidence of intent 
to end one s life 
can be explicit 
or inferred from 
the behavior or circumstances. A suicide attempt 
may or may not 
result 
in actual 
self-injury. If the individual 
is dissuaded by another person or changes his or her 
mind before initiating the behavior, this category does not apply. 


Current Suicidal Behavior 


T14.91A 
Initial encounter: If suicidal behavior is part of the initial encounter with the clinical 
presentation 


T14.91D 
Subsequent encounter: If suicidal behavior is part of subsequent encounters with the 
clinical presentation 


Z91.51 
History of Suicidal Behavior 


If suicidal behavior has occurred during the individual s lifetime 


Nonsuicidal 
Self-Injury 


This category may be used for individuals who have engaged in intentional 
self-inflicted damage 



to their body of a sort 
likely to induce bleeding, bruising, or pain (e.g., cutting, burning, stabbing, 
hitting, excessive rubbing) in the absence of suicidal intent. 


R45.88 
Current Nonsuicidal Self-Injury 


If nonsuicidal self-injurious behavior is part of the clinical presentation 


Z91.52 
History of Nonsuicidal Self-Injury 


If nonsuicidal self-injurious behavior has occurred during the individual s lifetime 


Abuse and Neglect 


Maltreatment 
by a family member (e.g., caregiver, intimate adult 
partner) or by a nonrelative can 
be the area of current 
clinical 
focus, or such maltreatment 
can be an important 
factor in the 
assessment 
and treatment 
of individuals with mental 
disorders or other medical 
conditions. 
Because of the legal 
implications of abuse and neglect, care should be used in assessing these 
conditions and assigning these codes. Having a past history of abuse or 


823 


neglect 
can influence diagnosis and treatment 
response in a number of mental 
disorders, and may 
also be noted along with the diagnosis. 


For the following categories, in addition to listings of the confirmed or suspected event 
of 
abuse or neglect, other codes are provided for use if the current 
clinical 
encounter is to provide 
mental 
health services to either the victim 
or the perpetrator of the abuse or neglect. A separate 
code is also provided for designating a past history of abuse or neglect. 


Coding Note for ICD-10-CM Abuse and Neglect Conditions 


For T codes only, the 7th character should be coded as follows: 
A (initial 
encounter) Use while the individual 
is receiving active treatment 
for the 


condition (e.g., surgical 
treatment, emergency department 
encounter, evaluation and 


treatment by a new clinician); or 


D (subsequent encounter) Use for encounters after the individual 
has received active 


treatment 
for the condition and when he or she is receiving routine care for the condition 


during the healing or recovery phase (e.g., cast 
change or removal, removal 
of external 
or 


internal fixation device, medication adjustment, other aftercare and follow-up visits). 


Child Maltreatment and Neglect Problems 


Child 
Physical 
Abuse 


This category may be used when physical 
abuse of a child is a focus of clinical 
attention. Child 
physical 
abuse is nonaccidental 
physical 
injury to a child ranging from 
minor bruises to severe 
fractures or death occurring as a result 
of punching, beating, kicking, biting, shaking, throwing, 
stabbing, choking, hitting (with a hand, stick, strap, or other object), burning, or any other 
method that 
is inflicted by a parent, caregiver, or other individual 
who has responsibility for the 
child. Such injury is considered abuse regardless of whether the caregiver intended to hurt 
the 
child. Physical 
discipline, such as spanking or paddling, is not 
considered abuse as long as it 
is 



reasonable and causes no bodily injury to the child. 


Child Physical Abuse, Confirmed 


T74.12XA 
Initial encounter 
T74.12XD 
Subsequent encounter 


Child Physical Abuse, Suspected 


T76.12XA 
Initial encounter 
T76.12XD 
Subsequent encounter 


Other Circumstances Related to Child Physical Abuse 


Z69.010 
Encounter for mental health services for victim of child physical abuse by parent 
Z69.020 
Encounter for mental health services for victim of nonparental child physical abuse 
Z62.810 
Personal history (past history) of physical abuse in childhood 
Z69.011 
Encounter for mental health services for perpetrator of parental child physical abuse 
Z69.021 
Encounter for mental health services for perpetrator of nonparental child physical 


abuse 


Child 
Sexual 
Abuse 


This category may be used when sexual 
abuse of a child is a focus of clinical 
attention. Child 
sexual 
abuse encompasses any sexual 
act 
involving a child that 
is intended to provide sexual 
gratification to a parent, caregiver, or other individual who has responsibility 


824 


for the child. Sexual 
abuse includes activities such as fondling a child s genitals, penetration, 
incest, rape, sodomy, and indecent 
exposure. Sexual 
abuse also includes noncontact 
exploitation 
of a child by a parent 
or caregiver for example, forcing, tricking, enticing, threatening, or 
pressuring a child to participate in acts for the sexual 
gratification of others, without 
direct 
physical contact between child and abuser. 


Child Sexual Abuse, Confirmed 


T74.22XA 
Initial encounter 
T74.22XD 
Subsequent encounter 


Child Sexual Abuse, Suspected 


T76.22XA 
Initial encounter 
T76.22XD 
Subsequent encounter 


Other Circumstances Related to Child Sexual Abuse 



Z69.010 
Encounter for mental health services for victim of child sexual abuse by parent 
Z69.020 
Encounter for mental health services for victim of nonparental child sexual abuse 
Z62.810 
Personal history (past history) of sexual abuse in childhood 
Z69.011 
Encounter for mental health services for perpetrator of parental child sexual abuse 
Z69.021 
Encounter for mental health services for perpetrator of nonparental child sexual abuse 


Child 
Neglect 


This category may be used when child neglect 
is a focus of clinical 
attention. Child neglect 
is 
defined as any confirmed or suspected egregious act 
or omission by a child s parent 
or other 
caregiver that 
deprives the child of basic age-appropriate needs and thereby results, or has 
reasonable potential 
to result, in physical 
or psychological 
harm 
to the child. Child neglect 
encompasses abandonment; 
lack of appropriate supervision; failure to attend to necessary 
emotional 
or psychological 
needs; 
and failure to provide necessary education, medical 
care, 
nourishment, shelter, and/or clothing. 


Child Neglect, Confirmed 


T74.02XA 
Initial encounter 
T74.02XD 
Subsequent encounter 


Child Neglect, Suspected 


T76.02XA 
Initial encounter 
T76.02XD 
Subsequent encounter 


Other Circumstances Related to Child Neglect 


Z69.010 
Encounter for mental health services for victim of child neglect by parent 
Z69.020 
Encounter for mental health services for victim of nonparental child neglect 
Z62.812 
Personal history (past history) of neglect in childhood 
Z69.011 
Encounter for mental health services for perpetrator of parental child neglect 
Z69.021 
Encounter for mental health services for perpetrator of nonparental child neglect 


825 


Child 
Psychological 
Abuse 


This category may be used when psychological 
abuse of a child is a focus of clinical 
attention. 
Child psychological 
abuse is nonaccidental 
verbal 
or symbolic acts by a child s parent 
or 
caregiver that 
result, or have reasonable potential 
to result, in significant 
psychological 
harm 
to 
the child. (Physical 
and sexual 
abusive acts are not 
included in this category.) Examples of 
psychological 
abuse of a child include berating, disparaging, or humiliating the child; 
threatening 
the child; 
harming/abandoning or indicating that 
the alleged offender will 
harm/abandon  
people or things that 
the child cares about; 
confining the child (as by tying a child s arms or legs 



together or binding a child to furniture or another object, or confining a child to a small 
enclosed 
area [e.g., a closet]); 
egregious scapegoating of the child; 
coercing the child to inflict 
pain on 
himself or herself; 
and disciplining the child excessively (i.e., at 
an extremely high frequency or 
duration, even if not at a level of physical abuse) through physical or nonphysical means. 


Child Psychological Abuse, Confirmed 


T74.32XA 
Initial encounter 
T74.32XD 
Subsequent encounter 


Child Psychological Abuse, Suspected 


T76.32XA 
Initial encounter 
T76.32XD 
Subsequent encounter 


Other Circumstances Related to Child Psychological Abuse 


Z69.010 
Encounter for mental health services for victim of child psychological abuse by parent 
Z69.020 
Encounter for mental health services for victim of nonparental child psychological 


abuse 
Z62.811 
Personal history (past history) of psychological abuse in childhood 
Z69.011 
Encounter for mental health services for perpetrator of parental child psychological 


abuse 
Z69.021 
Encounter for mental health services for perpetrator of nonparental child 


psychological abuse 


Adult Maltreatment and Neglect Problems 


826 


Spouse 
or Partner Violence, 
Physical 


This category may be used when spouse or partner physical 
violence is a focus of clinical 
attention. Spouse or partner physical 
violence is nonaccidental 
acts of physical 
force that 
result, 
or have reasonable potential 
to result, in physical 
harm 
to an intimate partner or that 
evoke 
significant 
fear in the partner. Nonaccidental 
acts of physical 
force include shoving, slapping, 
hair pulling, pinching, restraining, shaking, throwing, biting, kicking, hitting with the fist 
or an 
object, burning, poisoning, applying force to the throat, cutting off the air supply, holding the 
head under water, and using a weapon. Acts for the purpose of physically protecting oneself or 
one s partner are excluded. 


Spouse or Partner Violence, Physical, Confirmed 


T74.11XA 
Initial encounter 
T74.11XD 
Subsequent encounter 



Spouse or Partner Violence, Physical, Suspected 


T76.11XA 
Initial encounter 
T76.11XD 
Subsequent encounter 


Other Circumstances Related to Spouse or Partner Violence, Physical 


Z69.11 
Encounter for mental health services for victim of spouse or partner violence, physical 
Z91.410 
Personal history (past history) of spouse or partner violence, physical 
Z69.12 
Encounter for mental health services for perpetrator of spouse or partner violence, 


physical 


Spouse 
or Partner Violence, 
Sexual 


This category may be used when spouse or partner sexual 
violence is a focus of clinical 
attention. Spouse or partner sexual 
violence involves the use of physical 
force or psychological 
coercion to compel the partner to engage in a sexual act against his or her will, whether or not the 
act 
is completed. Also included in this category are sexual 
acts with an intimate partner who is 
unable to consent. 


Spouse or Partner Violence, Sexual, Confirmed 


T74.21XA 
Initial encounter 
T74.21XD 
Subsequent encounter 


Spouse or Partner Violence, Sexual, Suspected 


T76.21XA 
Initial encounter 
T76.21XD 
Subsequent encounter 


Other Circumstances Related to Spouse or Partner Violence, Sexual 


Z69.81 
Encounter for mental health services for victim of spouse or partner violence, sexual 
Z91.410 
Personal history (past history) of spouse or partner violence, sexual 
Z69.12 
Encounter for mental health services for perpetrator of spouse or partner violence, 


sexual 


Spouse 
or Partner Neglect 


This category may be used when spouse or partner neglect 
is a focus of clinical 
attention. Spouse 
or partner neglect 
is any egregious act 
or omission by one partner that 
deprives a dependent 
partner of basic needs and thereby results, or has reasonable potential 
to result, in physical 
or 
psychological 
harm 
to the dependent 
partner. This category may be used in the context 
of 
relationships in which one partner is extremely dependent 
on the other partner for care or for 
assistance in navigating ordinary daily activities for example, a partner who is incapable of 
self-care because of substantial 
physical, psychological/intellectual, or cultural 
limitations (e.g., 
inability to communicate with others and manage everyday activities as a result 
of living in a 
foreign culture). 



Spouse or Partner Neglect, Confirmed 


T74.01XA 
Initial encounter 
T74.01XD 
Subsequent encounter 


827 


Spouse or Partner Neglect, Suspected 


T76.01XA 
Initial encounter 
T76.01XD 
Subsequent encounter 


Other Circumstances Related to Spouse or Partner Neglect 


Z69.11 
Encounter for mental health services for victim of spouse or partner neglect 
Z91.412 
Personal history (past history) of spouse or partner neglect 
Z69.12 
Encounter for mental health services for perpetrator of spouse or partner neglect 


Spouse 
or Partner Abuse, 
Psychological 


This category may be used when spouse or partner psychological 
abuse is a focus of clinical 
attention. Spouse or partner psychological 
abuse encompasses nonaccidental 
verbal 
or symbolic 
acts by one partner that 
result, or have reasonable potential 
to result, in significant 
harm 
to the 
other partner. Acts of psychological 
abuse include berating or humiliating the victim; 
interrogating the victim; 
restricting the victim s ability to come and go freely; 
obstructing the 
victim s access to assistance (e.g., law enforcement; 
legal, protective, or medical 
resources); 
threatening the victim 
with physical 
harm 
or sexual 
assault; 
harming, or threatening to harm, 
people or things that 
the victim 
cares about; 
unwarranted restriction of the victim s access to or 
use of economic resources; 
isolating the victim 
from 
family, friends, or social 
support 
resources; 
stalking the victim; and trying to make the victim question his or her sanity ( gaslighting ). 


Spouse or Partner Abuse, Psychological, Confirmed 


T74.31XA 
Initial encounter 
T74.31XD 
Subsequent encounter 


Spouse or Partner Abuse, Psychological, Suspected 


T76.31XA 
Initial encounter 
T76.31XD 
Subsequent encounter 


Other Circumstances Related to Spouse or Partner Abuse, Psychological 


Z69.11 
Encounter for mental health services for victim of spouse or partner psychological 
abuse 


Z91.411 
Personal history (past history) of spouse or partner psychological abuse 



Z69.12 
Encounter for mental health services for perpetrator of spouse or partner 
psychological abuse 


Adult Abuse 
by 
Nonspouse 
or Nonpartner 


This category may be used when the abuse of an adult 
by another adult 
who is not 
an intimate 
partner is a focus of clinical attention. Such maltreatment may involve acts of physical, sexual, or 
emotional 
abuse. Examples of adult 
abuse include nonaccidental 
acts of physical 
force (e.g., 
pushing/shoving, scratching, slapping, throwing something that 
could hurt, punching, biting) that 
have resulted or have reasonable potential 
to result in physical 
harm 
or have caused 
significant 
fear; 
forced or coerced sexual 
acts; 
and verbal 
or symbolic acts with the potential 
to 
cause psychological 
harm 
(e.g., berating or humiliating the person; 
interrogating the person; 
restricting the person s ability to come and go freely; 
obstructing the person s access to 
assistance; 
threatening the person; 
harming or threatening to harm 
people or things that 
the 
person cares about; restricting the person s 


828 


access to or use of economic resources; 
isolating the person from 
family, friends, or social 
support 
resources; 
stalking the person; 
trying to make the person think that 
he or she is crazy). 
Acts for the purpose of physically protecting oneself or the other person are excluded. 


Adult Physical Abuse by Nonspouse or Nonpartner, Confirmed 


T74.11XA 
Initial encounter 
T74.11XD 
Subsequent encounter 


Adult Physical Abuse by Nonspouse or Nonpartner, Suspected 


T76.11XA 
Initial encounter 
T76.11XD 
Subsequent encounter 


Adult Sexual Abuse by Nonspouse or Nonpartner, Confirmed 


T74.21XA 
Initial encounter 
T74.21XD 
Subsequent encounter 


Adult Sexual Abuse by Nonspouse or Nonpartner, Suspected 


T76.21XA 
Initial encounter 
T76.21XD 
Subsequent encounter 


Adult Psychological Abuse by Nonspouse or Nonpartner, Confirmed 


T74.31XA 
Initial encounter 
T74.31XD 
Subsequent encounter 


Adult Psychological Abuse by Nonspouse or Nonpartner, Suspected 



T76.31XA 
Initial encounter 
T76.31XD 
Subsequent encounter 


Other Circumstances Related to Adult Abuse by Nonspouse or Nonpartner 


Z69.81 
Encounter for mental health services for victim of nonspousal or nonpartner adult 
abuse 


Z69.82 
Encounter for mental health services for perpetrator of nonspousal or nonpartner adult 
abuse 


Relational Problems 


Key relationships, especially intimate adult 
partner relationships and parent/caregiver-child 
relationships, have a significant 
impact 
on the health of the individuals in these relationships. 
These relationships can be health promoting and protective, neutral, or detrimental 
to health 
outcomes. In the extreme, these close relationships can be associated with maltreatment 
or 
neglect, which has significant 
medical 
and psychological 
consequences for the affected 
individual. A relational 
problem 
may come to clinical 
attention either as the reason that 
the 
individual 
seeks health care or as a problem 
that 
affects the course, prognosis, or treatment 
of the 
individual s mental disorder or other medical condition. 


829 


Parent-Child Relational Problem 
Z62.820 
Parent Biological Child 
Z62.821 
Parent Adopted Child 
Z62.822 
Parent Foster Child 
Z62.898 
Other Caregiver Child 


For this category, the term 
parent 
is used to refer to one of the child s primary caregivers, who 
may be a biological, adoptive, or foster parent 
or may be another relative (such as a grandparent) 
who fulfills a parental 
role for the child. This category may be used when the main focus of 
clinical 
attention is to address the quality of the parent-child relationship or when the quality of 
the parent-child relationship is affecting the course, prognosis, or treatment 
of a mental 
disorder 
or other medical 
condition. Typically, the parent-child relational 
problem 
is associated with 
impaired functioning in behavioral, cognitive, or affective domains. Examples of behavioral 
problems include inadequate parental 
control, supervision, and involvement 
with the child; 
parental 
overprotection; 
excessive parental 
pressure; 
arguments that 
escalate to threats of 
physical 
violence; 
and avoidance without 
resolution of problems. Cognitive problems may 
include negative attributions of the other s intentions, hostility toward or scapegoating of the 
other, and unwarranted feelings of estrangement. Affective problems may include feelings of 
sadness, apathy, or anger about 
the other individual 
in the relationship. Clinicians should take 
into account the developmental needs of the child and the cultural context. 


Z62.891 
Sibling Relational Problem 



This category may be used when the focus of clinical 
attention is a pattern of interaction among 
siblings that 
is associated with significant 
impairment 
in individual 
or family functioning or with 
development 
of symptoms in one or more of the siblings, or when a sibling relational 
problem 
is 
affecting the course, prognosis, or treatment 
of a sibling s mental 
disorder or other medical 
condition. This category may be used for either children or adults if the focus is on the sibling 
relationship. Siblings in this context include full, half-, step-, foster, and adopted siblings. 


Z63.0 
Relationship Distress With Spouse or Intimate Partner 


This category may be used when the major focus of the clinical 
contact 
is to address the quality 
of the intimate (spouse or partner) relationship or when the quality of that 
relationship is 
affecting the course, prognosis, or treatment 
of a mental 
disorder or other medical 
condition. 
Partners can be of the same or different 
genders. Typically, the relationship distress is associated 
with impaired functioning in behavioral, cognitive, or affective domains. Examples of behavioral 
problems include conflict 
resolution difficulty, withdrawal, and overinvolvement. Cognitive 
problems can manifest 
as chronic negative attributions of the other s intentions or dismissals of 
the partner s positive behaviors. Affective problems would include chronic sadness, apathy, 
and/or anger about the other partner. 


Problems Related to the Family Environment 


Z62.29 
Upbringing Away From Parents 


This category may be used when the main focus of clinical 
attention pertains to issues regarding 
a child being raised away from 
the parents or when this separate upbringing affects the course, 
prognosis, or treatment 
of a mental 
disorder or other medical 
condition. The child could be one 
who is under state custody and placed in kin care or foster care. The child could also be one who 
is living in a nonparental 
relative s home, or with friends, but 
whose out-of-home placement 
is 
not 
mandated or sanctioned by the courts. Problems related to a child living in a group home or 
orphanage are also included. This category excludes issues related to Z59.3 Problem 
Related to 
Living in a Residential Institution. 


830 


Z62.898 
Child Affected by Parental Relationship Distress 


This category may be used when the focus of clinical 
attention is the negative effects of parental 
relationship discord (e.g., high levels of conflict, distress, or disparagement) on a child in the 
family, including effects on the child s mental disorder or other medical condition. 


Z63.5 
Disruption of Family by Separation or Divorce 


This category may be used when partners in an intimate adult 
couple are living apart 
because of 
relationship problems or are in the process of divorce. 


Z63.8 
High Expressed Emotion Level Within Family 


Expressed emotion 
is a construct 
used as a qualitative measure of the  amount  of emotion in 
particular, hostility, emotional 
overinvolvement, and criticism 
directed toward a family member 
who is an identified patient displayed in the family environment. This category may be used 
when a family s high level 
of expressed emotion is the focus of clinical 
attention or is affecting 
the course, prognosis, or treatment 
of a family member s mental 
disorder or other medical 



condition. 


Educational Problems 


These categories may be used when an academic or educational 
problem 
is the focus of clinical 
attention or has an impact 
on the individual s diagnosis, treatment, or prognosis. Problems to be 
considered include illiteracy or low-level 
literacy; 
lack of access to schooling owing to 
unavailability or unattainability; 
problems with academic performance (e.g., failing school 
examinations, receiving failing marks or grades) or underachievement 
(below what 
would be 
expected given the individual s intellectual 
capacity); 
discord with teachers, school 
staff, or other 
students; 
problems related to inadequate teaching; 
and any other problems related to education 
and/or literacy. 


Z55.0 
Illiteracy and Low-Level Literacy 
Z55.1 
Schooling Unavailable and Unattainable 
Z55.2 
Failed School Examinations 
Z55.3 
Underachievement in School 
Z55.4 
Educational Maladjustment and Discord With Teachers and Classmates 
Z55.8 
Problems Related to Inadequate Teaching 
Z55.9 
Other Problems Related to Education and Literacy 


Occupational Problems 


These categories may be used when an occupational 
problem 
is the focus of clinical 
attention or 
has an impact 
on the individual s treatment 
or prognosis. Areas to be considered include 
problems with employment 
or in the work environment, including problems related to current 
military deployment 
status; 
unemployment; 
recent 
change of job; 
threat 
of job loss; 
stressful 
work schedule; 
uncertainty about 
career choices; 
sexual 
harassment 
on the job; 
other discord 
with boss, supervisor, co-workers, or others in the work environment; 
uncongenial 
or hostile 
work environments; 
other physical 
or mental 
strain related to work; 
sexual 
harassment 
on the 
job; and any other problems related to employment and/or occupation. 


Z56.82 
Problem Related to Current Military Deployment Status 


This category may be used when an occupational 
problem 
directly related to an individual s 
military deployment 
status is the focus of clinical 
attention or has an impact 
on the individual s 
diagnosis, treatment, or prognosis. Psychological 
reactions to deployment 
are not 
included in this 
category; 
such reactions would be better captured as an adjustment 
disorder or another mental 
disorder. 


831 


Z56.0 
Unemployment 
Z56.1 
Change of Job 



Z56.2 
Threat of Job Loss 
Z56.3 
Stressful Work Schedule 
Z56.4 
Discord With Boss and Workmates 
Z56.5 
Uncongenial Work Environment 
Z56.6 
Other Physical and Mental Strain Related to Work 
Z56.81 
Sexual Harassment on the Job 
Z56.9 
Other Problem Related to Employment 


Housing Problems 


Z59.01 
Sheltered Homelessness 


This category may be used when sheltered homelessness has an impact 
on an individual s 
treatment 
or prognosis. An individual 
is considered to be experiencing sheltered homelessness if 
the primary nighttime residence is a homeless shelter, a warming shelter, a domestic violence 
shelter, a motel, or in a temporary or transitional living situation. 


Z59.02 
Unsheltered Homelessness 


This category may be used when unsheltered homelessness has an impact 
on an individual s 
treatment 
or prognosis. An individual 
is considered to be experiencing unsheltered homelessness 
if residing in a place not 
meant 
for human habitation, such as a public space (e.g., tunnel, 
transportation station, mall), a building not 
intended for residential 
use (e.g., abandoned 
structure, unused factory), a car, a cave, a cardboard box, or some other ad hoc housing situation. 


Z59.1 
Inadequate Housing 


This category may be used when lack of adequate housing has an impact 
on an individual s 
treatment 
or prognosis. Examples of inadequate housing conditions include lack of heat 
(in cold 
temperatures) or electricity, infestation by insects or rodents, inadequate plumbing and toilet 
facilities, overcrowding, lack of adequate sleeping space, and excessive noise. It 
is important 
to 
consider cultural norms before assigning this category. 


Z59.2 
Discord With Neighbor, Lodger, or Landlord 


This category may be used when discord with neighbors, lodgers, or a landlord is a focus of 
clinical attention or has an impact on the individual s treatment or prognosis. 


Z59.3 
Problem Related to Living in a Residential Institution 


This category may be used when a problem 
(or problems) related to living in a residential 
institution is a focus of clinical 
attention or has an impact 
on the individual s treatment 
or 
prognosis. Psychological 
reactions to a change in living situation are not 
included in this 
category; such reactions would be better captured as an adjustment disorder. 


Z59.9 
Other Housing Problem 


This category may be used when there is a problem 
related to housing circumstances other than 
as specified above. 



Economic Problems 


These categories may be used when an economic problem 
is the focus of clinical 
attention or has 
an impact 
on the individual s treatment 
or prognosis. Areas to be considered include lack of 
adequate food (food insecurity) or safe drinking water, extreme poverty, low income, insufficient 
social or health insurance or welfare support, or any other economic problems. 


832 


Z59.41 
Food Insecurity 
Z58.6 
Lack of Safe Drinking Water 
Z59.5 
Extreme Poverty 
Z59.6 
Low Income 
Z59.7 
Insufficient Social or Health Insurance or Welfare Support 


This category may be used for individuals who meet 
eligibility criteria for social 
or welfare 
support 
but 
are not 
receiving such support, who receive support 
that 
is insufficient 
to address 
their needs, or who otherwise lack access to needed insurance or support 
programs. Examples 
include inability to qualify for welfare support 
because of lack of proper documentation or 
evidence of address, inability to obtain adequate health insurance because of age or a preexisting 
condition, and denial of support owing to excessively stringent income or other requirements. 


Z59.9 
Other Economic Problem 


This category may be used when there is a problem 
related to economic circumstances other than 
as specified above. 


Problems Related to the Social Environment 


Z60.2 
Problem Related to Living Alone 


This category may be used when a problem 
associated with living alone is the focus of clinical 
attention or has an impact 
on the individual s treatment 
or prognosis. Examples of such problems 
include chronic feelings of loneliness, isolation, and lack of structure in carrying out 
activities of 
daily living (e.g., irregular meal 
and sleep schedules, inconsistent 
performance of home 
maintenance chores). 


Z60.3 
Acculturation Difficulty 


This category may be used when difficulty in adjusting to a new culture (e.g., following 
migration) is the focus of clinical 
attention or has an impact 
on the individual s treatment 
or 
prognosis. 


Z60.4 
Social Exclusion or Rejection 


This category may be used when there is an imbalance of social 
power such that 
there is 
recurrent 
social 
exclusion or rejection by others. Examples of social 
rejection include bullying, 
teasing, and intimidation by others; 
being targeted by others for verbal 
abuse and humiliation; 
and being purposefully excluded from the activities of peers, workmates, or others in one s social 
environment. 



Z60.5 
Target of (Perceived) Adverse Discrimination or Persecution 


This category may be used when there is perceived or experienced discrimination against 
or 
persecution of the individual 
based on his or her membership (or perceived membership) in a 
specific category. Typically, such categories include gender or gender identity, race, ethnicity, 
religion, sexual 
orientation, country of origin, political 
beliefs, disability status, caste, social 
status, weight, and physical appearance. 


Z60.9 
Other Problem Related to Social Environment 


This category may be used when there is a problem 
related to the individual s social 
environment 
other than as specified above. 


Problems Related to Interaction With the Legal System 


These categories may be used when a problem 
related to interaction with the legal 
system 
is the 
focus of clinical 
attention or has an impact 
on the individual s treatment 
or prognosis. Areas to 
be considered include conviction in criminal 
proceedings, imprisonment 
or other incarceration, 
problems related to release from 
prison, and problems related to other legal 
circumstances (e.g., 
civil litigation, child custody or support proceedings). 


833 


Z65.0 
Conviction in Criminal Proceedings Without Imprisonment 
Z65.1 
Imprisonment or Other Incarceration 
Z65.2 
Problems Related to Release From Prison 
Z65.3 
Problems Related to Other Legal Circumstances (e.g., civil litigation, child 


custody or support proceedings) 


Problems Related to Other Psychosocial, 
Personal, 
and 
Environmental Circumstances 


Z72.9 
Problem Related to Lifestyle 


This category may be used when a lifestyle problem 
is a specific focus of treatment 
or directly 
affects the course, prognosis, or treatment 
of a mental 
disorder or other medical 
condition. 
Examples of lifestyle problems include lack of physical 
exercise, inappropriate diet, high-risk 
sexual 
behavior, and poor sleep hygiene. A problem 
that 
is attributable to a symptom 
of a mental 
disorder should not 
be coded unless that 
problem 
is a specific focus of treatment 
or directly 
affects the course, prognosis, or treatment 
of the individual. In such cases, both the mental 
disorder and the lifestyle problem should be coded. 


Z64.0 
Problems Related to Unwanted Pregnancy 
Z64.1 
Problems Related to Multiparity 
Z64.4 
Discord With Social Service Provider, Including Probation Officer, Case 


Manager, or Social Services Worker 



Z65.4 
Victim of Crime 
Z65.4 
Victim of Terrorism or Torture 
Z65.5 
Exposure to Disaster, War, or Other Hostilities 


Problems Related to Access to Medical and Other Health Care 


These categories may be used when a problem 
related to access to medical 
or other health care is 
the focus of clinical attention or has an impact on the individual s treatment or prognosis. 


Z75.3 
Unavailability or Inaccessibility of Health Care Facilities 
Z75.4 
Unavailability or Inaccessibility of Other Helping Agencies 


Circumstances of 
Personal History 


Z91.49 
Personal History of Psychological Trauma 
Z91.82 
Personal History of Military Deployment 


Other Health Service Encounters for Counseling and Medical 
Advice 


Z31.5 
Genetic Counseling 


This category may be used for individuals seeking genetic counseling to understand the risks of 
developing a mental 
disorder with a significant 
genetic component 
(e.g., bipolar disorder) for 
themselves and other family members, including their existing children, as well 
as the risks for 
their future children. 


834 


Z70.9 
Sex Counseling 


This category may be used when the individual 
seeks counseling related to sex education, sexual 
behavior, sexual 
orientation, sexual 
attitudes (embarrassment, timidity), others  sexual 
behavior 
or orientation (e.g., spouse, partner, child), sexual enjoyment, or any other sex-related issue. 


Z71.3 
Dietary Counseling 


This category may be used when the individual 
seeks counseling related to dietary issues like 
weight management. 


Z71.9 
Other Counseling or Consultation 


This category may be used when counseling is provided or advice/consultation is sought 
for a 
problem 
that 
is not 
specified above or elsewhere in this chapter (e.g., counseling regarding drug 
abuse prevention in an adolescent). 


Additional Conditions or Problems That 
May Be a Focus of 



Clinical Attention 


Z91.83 
Wandering Associated With a Mental Disorder 


This category may be used for individuals with a mental 
disorder whose desire to walk about 
leads to significant 
clinical 
management 
or safety concerns. For example, individuals with major 
neurocognitive or neurodevelopmental 
disorders may experience a restless urge to wander that 
places them 
at 
risk for falls and causes them 
to leave supervised settings without 
needed 
accompaniment. This category excludes individuals whose intent 
is to escape an unwanted 
housing situation (e.g., children who are running away from 
home, individuals who no longer 
wish to remain in the hospital) or those who walk or pace as a result 
of medication-induced 
akathisia. 


Coding note: 
First 
code associated mental 
disorder (e.g., major neurocognitive disorder, 


autism 
spectrum 
disorder), then code Z91.83 wandering associated with [specific mental 


disorder]. 


Z63.4 
Uncomplicated Bereavement 


This category may be used when the focus of clinical 
attention is a normal 
reaction to the death 
of a loved one. As part 
of their reaction to such a loss, some grieving individuals present 
with 
symptoms characteristic of a major depressive episode for example, feelings of sadness and 
associated symptoms such as insomnia, poor appetite, and weight 
loss. The bereaved individual 
typically regards the depressed mood as  normal,  although the individual 
may seek professional 
help for relief of associated symptoms such as insomnia or anorexia. The duration and 
expression of  normal  bereavement 
vary considerably among different 
cultural 
groups. Further 
guidance in distinguishing grief from 
a major depressive episode and from 
prolonged grief 
disorder is provided in their respective texts. 


Z60.0 
Phase of Life Problem 


This category may be used when a problem 
adjusting to a life-cycle transition (a particular 
developmental 
phase) is the focus of clinical 
attention or has an impact 
on the individual s 
treatment 
or prognosis. Examples of such transitions include entering or completing school, 
leaving parental 
control, getting married, starting a new career, becoming a parent, adjusting to 
an  empty nest  after children leave home, and retiring. 


Z65.8 
Religious or Spiritual Problem 


This category may be used when the focus of clinical 
attention is a religious or spiritual 
problem. 
Examples include distressing experiences that 
involve loss or questioning of faith, problems 
associated with conversion to a new faith, or questioning of spiritual 
values that 
may not 
necessarily be related to an organized church or religious institution. 


835 


Z72.811 
Adult Antisocial Behavior 


This category may be used when the focus of clinical 
attention is adult 
antisocial 
behavior that 
is 
not 
attributable to a mental 
disorder (e.g., conduct 
disorder, antisocial 
personality disorder). 
Examples include the behavior of some professional 
thieves, racketeers, or dealers in illegal 
substances. 



Z72.810 
Child or Adolescent Antisocial Behavior 


This category may be used when the focus of clinical 
attention is antisocial 
behavior in a child or 
adolescent 
that 
is not 
attributable to a mental 
disorder (e.g., intermittent 
explosive disorder, 
conduct 
disorder). Examples include isolated antisocial 
acts by children or adolescents (not 
a 
pattern of antisocial behavior). 


Z91.19 
Nonadherence to Medical Treatment 


This category may be used when the focus of clinical 
attention is nonadherence to an important 
aspect 
of treatment 
for a mental 
disorder or another medical 
condition. Reasons for such 
nonadherence may include discomfort 
resulting from 
treatment 
(e.g., medication side effects), 
expense of treatment, personal 
value judgments or religious or cultural 
beliefs about 
the 
proposed treatment, age-related debility, and the presence of a mental 
disorder (e.g., 
schizophrenia, personality disorder). This category may be used only when the problem 
is 
sufficiently severe to warrant 
independent 
clinical 
attention and does not 
meet 
diagnostic criteria 
for psychological factors affecting other medical conditions. 


E66.9 
Overweight or Obesity 


This category may be used when overweight or obesity is a focus of clinical attention. 


Z76.5 
Malingering 


The essential 
feature of malingering is the intentional 
production of false or grossly exaggerated 
physical 
or psychological 
symptoms, motivated by external 
incentives such as avoiding military 
duty, avoiding work, obtaining financial 
compensation, evading criminal 
prosecution, or 
obtaining drugs. Under some circumstances, malingering may represent 
adaptive behavior for 
example, feigning illness while a captive of the enemy during wartime. Malingering should be 
strongly considered if any combination of the following is noted: 


1. Medicolegal 
context 
of presentation (e.g., the individual 
is referred by an attorney to the 
clinician for examination, or the individual 
self-refers while litigation or criminal 
charges are 
pending). 
2. Marked discrepancy between the individual s claimed stress or disability and the objective 
findings and observations. 
3. Lack of cooperation during the diagnostic evaluation and in complying with the prescribed 
treatment regimen. 
4. The presence of antisocial personality disorder. 
Malingering differs from 
factitious disorder in that 
the motivation for the symptom 
production in malingering is an external 
incentive, whereas in factitious disorder external 
incentives are absent. Malingering is differentiated from 
functional 
neurological 
symptom 
disorder (conversion disorder) and other somatic symptom related mental 
disorders by the 
intentional 
production of symptoms and by the obvious external 
incentives associated with it. 
Definite evidence of feigning (such as clear evidence that 
loss of function is present 
during the 
examination but 
not 
at 
home) would suggest 
a diagnosis of factitious disorder if the individual s 
apparent 
aim 
is to assume the sick role, or malingering if it 
is to obtain an incentive, such as 
money. 


R41.81 
Age-Related Cognitive Decline 


This category may be used when the focus of clinical 
attention is an objectively identified 



decline in cognitive functioning consequent to the aging process that is within normal limits 


836 


given the individual s age. Individuals with this condition may report 
problems remembering 
names or appointments or may experience difficulty in solving complex problems. This category 
should be considered only after it 
has been determined that 
the cognitive impairment 
is not 
better 
explained by a specific mental disorder or attributable to a neurological condition. 


R41.83 
Borderline Intellectual Functioning 


This category may be used when an individual s borderline intellectual 
functioning is the focus 
of clinical 
attention or has an impact 
on the individual s treatment 
or prognosis. Differentiating 
borderline intellectual 
functioning and mild intellectual 
developmental 
disorder (intellectual 
disability) requires careful 
assessment 
of intellectual 
and adaptive functions and their 
discrepancies, particularly in the presence of co-occurring mental 
disorders that 
may affect 
patient 
compliance with standardized testing procedures (e.g., schizophrenia or attentiondeficit/
hyperactivity disorder, with severe impulsivity). 



837 



SECTION III 
Emerging Measures and Models 


Assessment Measures 


Cross-Cutting 
Symptom Measures 
DSM-5 
Self-Rated 
Level 1 
Cross-Cutting 
Symptom Measure Adult 
Parent/Guardian-Rated 
DSM-5 
Level 1 
Cross-Cutting 
Symptom Measure Child 


Age 
6 17 
Clinician-Rated 
Dimensions of 
Psychosis Symptom Severity 
World 
Health 
Organization 
Disability Assessment 
Schedule 
2.0 
(WHODAS 
2.0) 


Culture 
and 
Psychiatric 
Diagnosis 


Key Terms 


Cultural Formulation 


Core 
Cultural Formulation 
Interview (CFI) 


Cultural Formulation 
Interview (CFI) Informant 
Version 


Cultural Concepts of 
Distress 
Alternative 
DSM-5 
Model 
for Personality 
Disorders 
Conditions 
for Further Study 


Attenuated 
Psychosis Syndrome 
Depressive 
Episodes With 
Short-Duration 
Hypomania 
Caffeine 
Use 
Disorder 
Internet 
Gaming 
Disorder 
Neurobehavioral Disorder Associated 
With 
Prenatal Alcohol Exposure 
Suicidal Behavior Disorder 
Nonsuicidal Self-Injury Disorder 


838 


839 



This section 
contains tools and 
techniques to 
enhance 
clinical practice, 
understand 
the 
cultural context 
of 
mental disorders, 
and 
facilitate 
further study of 
proposed 
emerging 
diagnoses. 
The 
inclusion 
of 
this material represents a 
dynamic DSM-5 
that 
will evolve 
with 
advances in 
the 
field. 


Among 
the 
tools in 
Section 
III, 
Assessment 
Measures provides a 
Level 1 
crosscutting 
self/informant-rated 
measure 
that 
serves as a 
review of 
systems across mental 
disorders. 
A 
clinician-rated 
symptom severity scale 
for schizophrenia 
and 
other 
psychotic disorders also 
is provided, 
as well as the 
World 
Health 
Organization 
Disability 
Assessment 
Schedule, 
Version 
2 
(WHODAS 
2.0). 
Severity measures for symptoms 
identified 
by the 
Level 1 
cross-cutting 
self/informant-rated 
measure 
are 
available 
online 
(www.psychiatry.org/dsm5) and 
may be 
used 
to 
explore 
significant 
responses to 
the 
Level 1 
screen. 


A 
comprehensive 
review of 
the 
cultural context 
of 
mental disorders and 
the 
Cultural 
Formulation 
Interview (CFI) for clinical use 
are 
provided 
in 
the 
chapter  Culture 
and 
Psychiatric Diagnosis.  Both 
clinician 
and 
informant 
versions of 
the 
CFI 
are 
available 
online 
(www.psychiatry.org/dsm5). 
The 
chapter also 
contains a 
glossary of 
examples of 
cultural concepts of 
distress. 


The 
Alternative 
DSM-5 
Model for Personality Disorders provides an 
alternative 
to 
the 
extant 
personality disorders classification 
in 
Section 
II. 
This hybrid 
dimensional-
categorical model defines personality disorder in 
terms of 
impairments in 
personality 
functioning 
and 
pathological personality traits. 


Conditions for Further Study includes proposed 
criteria 
sets and 
descriptive 
text 
for 
new conditions that 
are 
the 
focus of 
active 
research, 
such 
as attenuated 
psychosis 
syndrome 
and 
caffeine 
use 
disorder. 


840 



841 



Assessment Measures 


A growing body 
of scientific evidence favors dimensional 
concepts in the diagnosis of 
mental 
disorders. Limitations of a categorical 
approach to diagnosis include the failure to find 
zones of rarity between diagnoses (i.e., delineation of mental 
disorders from 
one another by 
natural 
boundaries), need for intermediate categories like schizoaffective disorder, high rates of 
comorbidity, need for frequent 
use of other or unspecified diagnoses, relative lack of utility in 
furthering identification of unique antecedent 
validators for most 
mental 
disorders, and lack of 
treatment specificity for the various diagnostic categories. 


From 
both clinical 
and research perspectives, there is a need for a more dimensional 
approach that 
can be combined with DSM s set 
of categorical 
diagnoses to better capture the 
heterogeneity in the presentation of various mental 
and substance use disorders. Such an 
approach allows clinicians or others to better communicate particular variation of features that 
apply to presentations that 
meet 
criteria for a disorder. Such features include differential 
severity 
of individual 
symptoms (including symptoms that 
are part 
of the diagnostic features as well 
as 
those that 
are associated with the disorder) as measured by intensity, duration, and impact 
on 
functioning. This combined approach also allows clinicians or others to identify conditions that 
do not meet criteria for a disorder but are severe and disabling and in need of treatment. 


It is expected that as the understanding of basic disease mechanisms for mental and substance 
use disorders based on pathophysiology, neurocircuitry, and gene-environment 
interactions 
increases, more objective measures of psychopathology will 
be incorporated into the diagnostic 
criteria sets to enhance their accuracy. Until 
such time, a dimensional 
approach depending 
primarily on an individual s subjective reports of symptom 
experiences along with the clinician s 
interpretation is highlighted by current 
psychiatric evaluation guidelines as an important 
step in 
enhancing diagnostic practice. 


Cross-cutting symptom measures, modeled on general 
medicine s review of systems, can 
serve as an approach for reviewing critical 
psychopathological 
domains across age groups and 
diagnoses. The general 
medical 
review of systems a list 
of questions arranged by organ 
systems is crucial 
to detecting signs and symptoms of dysfunction and disease with which the 
individual 
may or may not 
present 
that 
can facilitate diagnosis and treatment. A similar review of 
various mental 
systems (or domains), which is the goal 
of the cross-cutting symptom 
measures, 
can aid in a more comprehensive mental 
status assessment 
of individuals at 
the initial 
evaluation. 
The review of mental 
systems can systematically draw attention to signs and symptoms of other 
domains of mental 
health and functioning that 
may be important 
to the individual s care. The 
cross-cutting measures have two levels of inquiry: 
Level 
1 uses 1 to 3 questions for each of 13 
symptom 
domains for adults (self-rated) and 12 domains for children (ages 6 17, parent 
rated) 
and adolescents (child rated, ages 11 17) to identify emerging signs and symptoms. Level 
2 
questions provide a more in-depth assessment 
of certain domains (e.g., depression, anxiety, 
mania, anger, irritability, somatic symptoms). These measures are developed to be administered 



both at 
initial 
interview and at 
follow-up visits. Thus, use of these measures can form 
key aspects 
of measurement-based care, the process by which standardized assessment tools are 


842 


administered and results used to track individuals  progress over time to guide a more precise 
plan of care. Use of these measures ultimately aims to inform 
measurement-based care by 
identifying areas of emerging symptoms and concerns as well 
as supporting ongoing symptom 
monitoring, treatment 
adjustment, and outcomes critical 
to the provision of quality care for 
individuals with mental 
and substance use disorders. As a result, these cross-cutting symptom 
measures have been identified as important 
components of psychiatric diagnostic assessment 
in 
clinical practice guidelines. 


Severity measures 
are disorder-specific, corresponding closely to the criteria that 
constitute 
the disorder definition. They may be administered to individuals who have received a diagnosis 
or who have a clinically significant 
syndrome that 
falls short 
of meeting full 
criteria for a 
diagnosis (e.g., use of the Clinician-Rated Dimensions of Psychosis Symptom 
Severity in 
individuals whose symptoms meet 
criteria for schizophrenia). Some of the assessments are self-
rated, while others are rated by the clinician based on observation of the individual. As with the 
cross-cutting symptom 
measures, these measures can be administered both at 
initial 
interview 
and over time to track the severity of the individual s disorder and response to treatment. These 
assessments help operationalize symptom 
frequency, intensity, or duration; 
overall 
symptom 
severity; 
or symptom 
type (e.g., depression, anxiety, sleep disturbance) for many, though not 
all, 
DSM-5 diagnoses (e.g., generalized anxiety disorder, social 
anxiety disorder, psychotic 
disorders, posttraumatic stress disorder, autism 
spectrum 
disorder, and social 
(pragmatic) 
communication disorder). Data obtained from 
use of these disorder-specific measures can assist 
with diagnosis and inform symptom monitoring and treatment planning. 


The World Health Organization Disability Assessment 
Schedule, Version 2.0 (WHODAS 


2.0) was developed by the World Health Organization to assess an individual s ability to perform 
activities in six areas: 
understanding and communicating; 
getting around; 
self-care; 
getting along 
with people; 
life activities (e.g., household, work/school); 
and participation in society. This 
version of the scale is self-administered and was developed for individuals with any medical 
condition, not 
just 
mental 
disorders. It 
corresponds to concepts contained in the WHO 
International 
Classification of Functioning, Disability and Health. This assessment 
can also be 
used over time to track changes in an individual s level 
of functioning. Assessment 
of 
functioning is a key aspect 
of psychiatric diagnostic assessment 
given that 
most 
DSM-5 criteria 
sets include a requirement 
that 
the disturbance causes clinically significant 
distress or 
impairment 
in functioning. Individuals with mental 
disorders are more likely to have severe 
impairment 
in functioning (i.e., communicating or understanding; 
getting along with others; 
carrying out 
daily activities at 
work, home, or school; 
participating in social 
activities) compared 
to individuals with chronic medical 
conditions. In addition, many individuals seek help for 
mental 
disorders because of the direct 
impact 
of their disorders on functional 
impairment 
across 
multiple domains and settings. Functional 
impairment 
may impact 
prognosis across diagnoses 
and, if residual 
functional 
impairment 
remains after symptoms subside, can lead to recurrence or 
relapse for conditions such as major depressive disorder and anxiety disorders. 
This chapter focuses on the DSM-5 Level 
1 Cross-Cutting Symptom 
Measure (adult 
self



rated and parent/guardian versions); 
the Clinician-Rated Dimensions of Psychosis Symptom 
Severity; 
and the WHODAS 
2.0. Clinician instructions, scoring information, and interpretation 
guidelines are included for each. Description of the child-rated version is not 
included in print 
given the overall 
similarity in items, scoring, and clinician instructions and guidelines with the 
parent/guardian-rated version. These measures, including the child-rated version, and additional 
dimensional 
assessments, such as those for diagnostic severity, can be found online at 
www.psychiatry.org/dsm5. 


843 


Cross-Cutting Symptom Measures 


Level 
1 Cross-Cutting Symptom Measure 


The DSM-5 Level 
1 Cross-Cutting Symptom 
Measure is a self- or informant-rated measure that 
assesses domains that 
are important 
across psychiatric diagnoses. It 
is intended to help clinicians 
identify additional 
areas of inquiry that 
may have significant 
impact 
on the individual s treatment 
and prognosis. In addition, the measure may be used to track changes in the individual s 
symptom presentation over time. 


The adult 
version of the measure consists of 23 questions that 
assess 13 psychiatric domains, 
including depression, anger, mania, anxiety, somatic symptoms, suicidal 
ideation, psychosis, 
sleep problems, memory, repetitive thoughts and behaviors, dissociation, personality functioning, 
and substance use (Table 1). Each domain consists of one to three questions. Each item 
inquires 
about 
how much (or how often) the individual 
has been bothered by the specific symptom 
during 
the past 
2 weeks. If the individual 
is of impaired capacity and unable to complete the form 
(e.g., 
an individual 
with major neurocognitive disorder), a knowledgeable adult 
informant 
may 
complete this measure. 


844 


TABLE 
1 
Adult DSM-5 
Self-Rated 
Level 
1 
Cross-Cutting 
Symptom Measure: 13 
domains, 
thresholds 
for further inquiry, 
and 
associated 
DSM-5 
Level 
2 
measures 


Threshold 
to 
guide 
DSM-5 
Level 
2 
Cross-Cutting 
Symptom 
Domain 
Domain 
name 
further inquiry 
Measurea 


I. 
Depression 
Mild or greater 
Level 2 Depression Adult (PROMIS 
Emotional Distress Short Form) 
II. 
Anger 
Mild or greater 
Level 2 Anger Adult (PROMIS Emotional 
Distress Anger Short Form) 
III. 
Mania 
Mild or greater 
Level 2 Mania Adult (Altman Self-Rating 
Mania Scale [ASRM]) 
IV. 
Anxiety 
Mild or greater 
Level 2 Anxiety Adult (PROMIS Emotional 
Distress Anxiety Short Form) 
V. 
Somatic symptoms 
Mild or greater 
Level 2 Somatic Symptom Adult (Patient 
Health Questionnaire 15 [PHQ-15] Somatic 
Symptom Severity Scale) 

VI. 
Suicidal ideation 
Slight or greater 
None 
VII. 
Psychosis 
Slight or greater 
None 
VIII. 
Sleep problems 
Mild or greater 
Level 2 Sleep Disturbance Adult (PROMIS 
Sleep Disturbance Short Form) 
IX. 
Memory 
Mild or greater 
None 
X. 
Repetitive thoughts and 
behaviors 
Mild or greater 
Level 2 Repetitive Thoughts and Behaviors  
Adult (Florida Obsessive-Compulsive Inventory 
[FOCI] Severity Scale) 
XI. 
Dissociation 
Mild or greater 
None 
XII. 
Personality functioning 
Mild or greater 
None 
XIII. 
Substance use 
Slight or greater 
Level 2 Substance Use Adult (adapted from 
the NIDA-Modified ASSIST) 


Note. NIDA = National Institute on Drug Abuse. 
aAvailable at 
www.psychiatry.org/dsm5. 


The measure was found to be clinically useful 
and to have good reliability in the DSM-5 
Field Trials that 
were conducted in adult 
clinical 
samples across the United States and in Canada. 
In the DSM-5 Field Trials, in which the individual s symptom 
ratings were shared with the 
clinician before meeting, individuals reported that 
the results from 
the measure helped facilitate 
communication during the clinical 
encounter. Similarly, clinicians in both major academic-
medical 
research institutions as well 
as routine clinical 
practice settings found the measures 
clinically useful 
and feasible for integration into everyday clinical 
care as well 
as specialty 
clinical 
settings. In addition to results from 
the DSM-5 Field Trials, several 
studies have 
evaluated the psychometric properties of the adult 
self-rated version of the cross-cutting 
symptom 
measure in a variety of populations. For example, findings from 
a large study of non-
treatment-seeking college students across the United States demonstrated acceptable internal 
consistency and internal validity. 


The parent/guardian-rated version of the measure (for children ages 6 17) consists of 25 
questions that 
assess 12 psychiatric domains, including depression, anger, irritability, mania, 
anxiety, somatic symptoms, inattention, suicidal 
ideation/attempt, psychosis, sleep disturbance, 
repetitive thoughts and behaviors, and substance use (Table 2). Each item 
asks the parent 
or 
guardian to rate how much (or how often) his or her child has been bothered by the specific 
psychiatric symptom 
during the past 
2 weeks. The measure was also found to be clinically useful 
and to have good reliability in the DSM-5 Field Trials that 
were conducted in pediatric clinical 
samples across the United States. For children ages 11 17, along with the parent/guardian rating 
of the child s symptoms, the clinician may consider having the child complete the child-rated 
version of the measure. The child-rated version of the measure can be found online at 
www.psychiatry.org/dsm5. 


845 


TABLE 
2 
Parent/guardian-rated 
DSM-5 
Level 
1 
Cross-Cutting 
Symptom Measure 
for child 
age 
6 17: 12 
domains, 
thresholds 
for further inquiry, 
and 
associated 
Level 
2 
measures 


Threshold 
to 
guide 
DSM-5 
Level 
2 
Cross-Cutting 
Symptom 



Domain 
Domain 
name 
further inquiry 
Measurea 
I. 
Somatic symptoms 
Mild or greater 
Level 2 Somatic Symptoms Parent/Guardian 
of Child Age 6 17 (Patient Health 
Questionnaire 15 [PHQ-15] Somatic Symptom 
Severity Scale) 
II. 
Sleep problems 
Mild or greater 
Level 2 Sleep Disturbance Parent/Guardian of 
Child Age 6 17 (PROMIS Sleep Disturbance  
Short Form) 
III. 
Inattention 
Slight or greater 
Level 2 Inattention Parent/Guardian of Child 
Age 6 17 (Swanson, Nolan, and Pelham, 
Version IV [SNAP-IV]) 
IV. 
Depression 
Mild or greater 
Level 2 Depression Parent/Guardian of Child 
Age 6 17 (PROMIS Emotional Distress  
Depression Parent Item Bank) 
V. 
Anger 
Mild or greater 
Level 2 Anger Parent/Guardian of Child 
(PROMIS Calibrated Anger Measure Parent) 
VI. 
Irritability 
Mild or greater 
Level 2 Irritability Parent/Guardian of Child 
(Affective Reactivity Index [ARI]) 
VII. 
Mania 
Mild or greater 
Level 2 Mania Parent/Guardian of Child Age 
6 17 (Altman Self-Rating Mania Scale 
[ASRM]) 
VIII. 
Anxiety 
Mild or greater 
Level 2 Anxiety Parent/Guardian of Child Age 
6 17 (PROMIS Emotional Distress Anxiety 
 Parent Item Bank) 
IX. 
Psychosis 
Slight or greater 
None 
X. 
Repetitive thoughts and 
behaviors 
Mild or greater 
None 
XI. 
Substance use 
Yes 
Level 2 Substance Use Parent/Guardian of 
Child Age 6 17 (adapted from the NIDA-
modified ASSIST) 
Don t Know 
NIDA-modified ASSIST (adapted) Child-Rated 
(age 11 17 years) 
XII. 
Suicidal ideation/suicide 
attempts 
Yes 
None 
Don t Know 
None 


Note. NIDA = National Institute on Drug Abuse. 
aAvailable at 
www.psychiatry.org/dsm5. 


Scoring 
and 
interpretation. 


On the adult 
self-rated version of the measure, each item 
is rated on a 
5-point 
scale (0 = none or not 
at 
all; 
1 = slight 
or rare, less than a day or two; 
2 = mild or several 
days; 
3 = moderate or more than half the days; 
and 4 = severe or nearly every day). The score on 
each item 
within a multi-item 
domain should be reviewed by the clinician, especially if a Level 
2 
cross-cutting symptom 
assessment 
is not 
indicated, to understand which specific symptom 
within 
a domain is most 
problematic (e.g., auditory hallucinations or thought 
broadcasting for the 
psychosis domain) to help guide further inquiry. However, a rating of mild (i.e., 2) or greater on 
any item 
within a domain, except 
for substance use, suicidal 
ideation, and psychosis, strongly 
suggests the need for 


846 


additional 
inquiry and follow-up to determine if a more detailed assessment 
is necessary, which 



may include the Level 
2 cross-cutting symptom 
assessment 
for the domain (see 1). For substance 
use, suicidal 
ideation, and psychosis, a rating of slight 
(i.e., 1) or greater on any item 
within the 
domain may serve as a guide for additional 
inquiry and follow-up to determine if a more detailed 
assessment 
is needed. As such, the rater should indicate the highest 
score within a domain in the 
 Highest 
domain score  column. Table 1 
outlines threshold scores that 
may guide further inquiry 
for the remaining domains. 


On the parent/guardian-rated version of the measure (for children ages 6 17), 19 of the 25 
items are each rated on a 5-point 
scale (0 = none or not 
at 
all; 
1 = slight 
or rare, less than a day or 
two; 
2 = mild or several 
days; 
3 = moderate or more than half the days; 
and 4 = severe or nearly 
every day). The suicidal 
ideation, suicide attempt, and substance abuse items are each rated on a 
 Yes, No, or Don t 
Know  scale. The score on each item 
within a domain should be reviewed by 
the clinician to understand which specific symptom 
within a domain is most 
problematic (e.g., 
visual or auditory hallucination on the psychosis domain) to help guide further inquiry. However, 
with the exception of inattention and psychosis, a rating of mild (i.e., 2) or greater on any item 
within a domain that 
is scored on the 5-point 
scale may serve as a guide for additional 
inquiry 
and follow-up to determine if a more detailed assessment 
is necessary, which may include the 
Level 
2 cross-cutting symptom 
assessment 
for the domain (see Table 2). For inattention or 
psychosis, a rating of slight 
or greater (i.e., 1 or greater) may be used as an indicator for 
additional 
inquiry. A parent 
or guardian s rating of  Don t 
Know  on the suicidal 
ideation, 
suicide attempt, and any of the substance use items, especially for children ages 11 17 years, 
may result 
in additional 
probing of the issues with the child, including using the child-rated 
Level 
2 Cross-Cutting Symptom 
Measure for the relevant 
domain. Because additional 
inquiry is 
made on the basis of the highest 
score on any item 
within a domain, clinicians should indicate 
that 
score in the  Highest 
Domain Score  column. Table 2 
outlines threshold scores that 
may 
guide further inquiry for the remaining domains. 


The clinician instructions and guidelines for the child-rated version are similar to those of the 
parent/guardian-rated version described above with the exception of the  Don t 
Know  response 
categories, which are not present in the child-rated version (see www.psychiatry.org/dsm5). 


Level 
2 Cross-Cutting Symptom Measures 


Any threshold scores on the Level 
1 Cross-Cutting Symptom 
Measure (as noted in Tables 1 
and 
2 
and described in  Scoring and Interpretation ) indicate a possible need for detailed clinical 
inquiry. Level 
2 Cross-Cutting Symptom 
Measures provide one method of obtaining more in-
depth information on potentially significant 
symptoms to inform 
diagnosis, treatment 
planning, 
and follow-up. They are available online at 
www.psychiatry.org/dsm5. Tables 1 
and 2 
outline 
each Level 
1 domain and identify the domains for which DSM-5 Level 
2 Cross-Cutting 
Symptom 
Measures are available for more detailed assessments. Adult 
and pediatric (parent 
and 
child) versions are available online for most Level 1 symptom domains. 


Frequency of Use of the Cross-Cutting Symptom Measures 


To track change in the individual s symptom 
presentation over time, the Level 
1 and relevant 
Level 
2 cross-cutting symptom 
measures may be completed at 
regular intervals as clinically 
indicated, depending on the stability of the individual s symptoms and treatment 
status. For 
individuals with impaired capacity and for children ages 6 17 years, it 
is preferable for the 



measures to be completed at 
follow-up appointments by the same knowledgeable informant 
and 
by the same parent 
or guardian. Consistently high scores on a particular domain may indicate 
significant 
and problematic symptoms for the individual 
that 
might 
warrant 
further assessment, 
treatment, and follow-up. Clinical judgment should guide decision making. 


847 


DSM-5 Self-Rated Level 
1 Cross-Cutting Symptom Measure Adult 


Name:______________________________________ 
Age: __________ 
Date:_____________ 
If the measure is being completed by an informant, what is your relationship with the individual?: ________________ 
In a typical week, approximately how much time do you spend with the individual? _________________________ 


hours/week 
Instructions: The questions below ask about things that might have bothered you. For each question, circle the number that best 
describes how much (or how often) you have been bothered by each problem during the past TWO (2) WEEKS. 


During 
the 
past 
TWO 
(2) 
WEEKS, 
how much 
(or 
how 
often) 
have 
you 
been 
bothered 
by the 
following 
problems? 
None 
Not 
at 
all 
Slight 
Rare, 
less 
than 
a 
day or 
two 
Mild 
Several 
days 
Moderate 
More 
than 
half 
the 
days 
Severe 
Nearly 
every 
day 
Highest 
Domain 
Score 
(clinician) 
I. 
1. 
Little interest or pleasure in 
doing things? 
0 
1 
2 
3 
4 
2. 
Feeling down, depressed, or 
hopeless? 
0 
1 
2 
3 
4 
II. 
3. 
Feeling more irritated, grouchy, 
angry than usual? 
0 
1 
2 
3 
4 
III. 
4. 
Sleeping less than usual, but 
still have a lot of energy? 
0 
1 
2 
3 
4 
5. 
Starting lots more projects than 
usual or doing more risky 
things than usual? 
0 
1 
2 
3 
4 
IV. 
6. 
Feeling nervous, anxious, 
frightened, worried, or on 
edge? 
0 
1 
2 
3 
4 
7. 
Feeling panic or being 
frightened? 
0 
1 
2 
3 
4 
8. 
Avoiding situations that make 
you anxious? 
0 
1 
2 
3 
4 
V. 
9. 
Unexplained aches and pains 
(e.g., head, back, joints, 
abdomen, legs)? 
0 
1 
2 
3 
4 
10. 
Feeling that your illnesses are 
not being taken seriously 
enough? 
0 
1 
2 
3 
4 
VI. 
11. 
Thoughts of actually hurting 
yourself? 
0 
1 
2 
3 
4 
848 
VII. 
12. 
Hearing things other people 
couldn t hear, such as voices 
even when no one was 
around? 
0 
1 
2 
3 
4 



13. 
Feeling that someone could hear 
your thoughts, or that youcould hear what another 
person was thinking? 
0 
1 
2 
3 
4 
VIII. 
14. 
Problems with sleep that 
affected your sleep quality 
overall? 
0 
1 
2 
3 
4 
IX. 
15. 
Problems with memory (e.g., 
learning new information) or 
with location (e.g., finding 
your way home)? 
0 
1 
2 
3 
4 
X. 
16. 
Unpleasant thoughts, urges, or 
images that repeatedly enter 
your mind? 
0 
1 
2 
3 
4 
17. 
Feeling driven to perform 
certain behaviors or mental 
acts over and over again? 
0 
1 
2 
3 
4 
XI. 
18. 
Feeling detached or distant from 
yourself, your body, your 
physical surroundings, or 
your memories? 
0 
1 
2 
3 
4 
XII. 
19. 
Not knowing who you really are 
or what you want out of life? 
0 
1 
2 
3 
4 
20. 
Not feeling close to other 
people or enjoying your 
relationships with them? 
0 
1 
2 
3 
4 
XIII. 
21. 
Drink at least 4 drinks of any 
kind of alcohol in a single 
day? 
0 
1 
2 
3 
4 
22. 
Smoke any cigarettes, a cigar, 
or pipe, or use snuff or 
chewing tobacco? 
0 
1 
2 
3 
4 
23. 
Use any of the following 
medicines ON YOUR OWN, 
that is, without a doctor s 
prescription, in greater 
amounts or longer than 
prescribed [e.g., painkillers 
(like Vicodin), stimulants 
(like Ritalin or Adderall), 
sedatives or tranquilizers 
(like sleeping pills or 
Valium), or drugs like 
marijuana, cocaine or crack, 
club drugs (like ecstasy), 
hallucinogens (like LSD), 
heroin, inhalants or solvents 
(like glue), or 
methamphetamine (like 
speed)]? 
0 
1 
2 
3 
4 


849 


Parent/Guardian-Rated DSM-5 Level 
1 Cross-Cutting Symptom 
Measure Child Age 6 17 



Child s Name:________________ 
Age: __________ 
Date:_____________ 


Relationship to the child: ___________________________________ 


Instructions (to parent or guardian of child): The questions below ask about things that might have bothered your child. For 
each question, circle the number that best describes how much (or how often) your child has been bothered by each problem 
during the past TWO (2) WEEKS. 


During 
the 
past 
TWO 
(2) 
WEEKS, 
how much 
(or 
how often) 
has your 
child  
None 
Not 
at 
all 
Slight 
Rare, 
less 
than 
a 
day or 
two 
Mild 
Several 
days 
Moderate 
More 
than 
half 
the 
days 
Severe 
Nearly 
every 
day 
Highest 
Domain 
Score 
(clinician) 
I. 
1. 
Complained of stomachaches, 
headaches, or other aches and 
pains? 
0 
1 
2 
3 
4 
2. 
Said he/she was worried about 
his/her health or about getting 
sick? 
0 
1 
2 
3 
4 
II. 
3. 
Had problems sleeping that is, 
trouble falling asleep, staying 
asleep, or waking up too early? 
0 
1 
2 
3 
4 
III. 
4. 
Had problems paying attention 
when he/she was in class or 
doing his/her homework or 
reading a book or playing a 
game? 
0 
1 
2 
3 
4 
IV. 
5. 
Had less fun doing things than 
he/she used to? 
0 
1 
2 
3 
4 
6. 
Seemed sad or depressed for 
several hours? 
0 
1 
2 
3 
4 
V. 
andVI. 
7. 
Seemed more irritated or easily 
annoyed than usual? 
0 
1 
2 
3 
4 
8. 
Seemed angry or lost his/her 
temper? 
0 
1 
2 
3 
4 
VII. 
9. 
Starting lots more projects than 
usual or doing more risky 
things than usual? 
0 
1 
2 
3 
4 
10. 
Sleeping less than usual for 
him/her but still has lots of 
energy? 
0 
1 
2 
3 
4 
VIII. 
11. 
Said he/she felt nervous, anxious, 
or scared? 
0 
1 
2 
3 
4 
12. 
Not been able to stop worrying? 
0 
1 
2 
3 
4 
13. 
Said he/she couldn t do things 
he/she wanted to or should 
have done because they made 
him/her feel nervous? 
0 
1 
2 
3 
4 
850 
IX. 
14. 
Said that he/she heard voices  
when there was no one there  
speaking about him/her or 
telling him/her what to do or 
saying bad things to him/her? 
0 
1 
2 
3 
4 
15. 
Said that he/she had a vision when 
he/she was completely awake 
0 
1 
2 
3 
4 



 that is, saw something or 
someone that no one else could 
see? 
X. 
16. 
Said that he/she had thoughts that 
kept coming into his/her mind 
that he/she would do something 
bad or that something bad 
would happen to him/her or to 
someone else? 
0 
1 
2 
3 
4 
17. 
Said he/she felt the need to check 
on certain things over and over 
again, like whether a door was 
locked or whether the stove 
was turned off? 
0 
1 
2 
3 
4 
18. 
Seemed to worry a lot about 
things he/she touched being 
dirty or having germs or being 
poisoned? 
0 
1 
2 
3 
4 
19. 
Said that he/she had to do things 
in a certain way, like counting 
or saying special things out 
loud, in order to keep 
something bad from 
happening? 
0 
1 
2 
3 
4 
In 
the 
past 
TWO 
(2) 
WEEKS, 
has your 
child   
XI. 
20. 
Had an alcoholic beverage (beer, 
wine, liquor, etc.)? 
. Yes 
. No 
. Don t Know 
21. 
Smoked a cigarette, a cigar, or 
pipe, or used snuff or chewing 
tobacco? 
. Yes 
. No 
. Don t Know 
22. 
Used drugs like marijuana, 
cocaine or crack, club drugs 
(like ecstasy), hallucinogens 
(like LSD), heroin, inhalants or 
solvents (like glue), or 
methamphetamine (like speed)? 
. Yes 
. No 
. Don t Know 
23. 
Used any medicine without a 
doctor s prescription (e.g., 
painkillers [like Vicodin], 
stimulants [like Ritalin or 
Adderall], sedatives or 
tranquilizers [like sleeping pills 
or Valium], or steroids)? 
. Yes 
. No 
. Don t Know 
XII. 
24. 
In the past TWO (2) WEEKS, 
has he/she talked about wanting 
to kill himself/herself or about 
wanting to commit suicide? 
. Yes 
. No 
. Don t Know 
25. 
Has he/she EVER tried to kill 
himself/herself? 
. Yes 
. No 
. Don t Know 


851 


Clinician-Rated Dimensions of 
Psychosis Symptom Severity 


As described in the chapter  Schizophrenia Spectrum 
and Other Psychotic Disorders,  psychotic 
disorders are heterogeneous, and symptom 
severity can predict 
important 
aspects of the illness, 



such as the degree of cognitive and/or neurobiological 
deficits. Dimensional 
assessments capture 
meaningful 
variation in the severity of symptoms, which may help with treatment 
planning, 
prognostic decision-making, and research on pathophysiological 
mechanisms. The Clinician-
Rated Dimensions of Psychosis Symptom 
Severity measure provides scales for the dimensional 
assessment 
of the primary symptoms of psychosis, including hallucinations, delusions, 
disorganized speech, abnormal 
psychomotor behavior, and negative symptoms. A scale for the 
dimensional 
assessment 
of cognitive impairment 
is also included. Many individuals with 
psychotic disorders have impairments in a range of cognitive domains, which predict 
functional 
abilities and prognosis. In addition, scales for dimensional 
assessment 
of depression and mania 
are provided, which may alert 
clinicians to co-occurring mood pathology. The severity of mood 
symptoms in psychosis has prognostic value and can guide treatment. 


The Clinician-Rated Dimensions of Psychosis Symptom 
Severity is an 8-item 
measure that 
may be completed by the clinician at 
the time of the clinical 
assessment. Each item 
asks the 
clinician to rate the severity of each symptom 
as experienced by the individual 
when it 
was at 
its 
most severe during the past 7 days. 


Scoring and Interpretation 


Each item 
on the measure is rated on a 5-point 
scale (0 = none; 
1 = equivocal; 
2 = present, but 
mild; 
3 = present 
and moderate; 
and 4 = present 
and severe) with a symptom-specific definition 
of each rating level. The clinician reviews all 
of the individual s available information and, based 
on clinical 
judgment, selects (with checkmark) the level 
that 
most 
accurately describes the 
severity of the symptom 
domain. The clinician then indicates the score for each item 
in the 
 Score  column provided. 


Frequency of Use 


To track changes in the individual s symptom 
severity over time, the measure may be completed 
at 
regular intervals as clinically indicated, depending on the stability of the individual s 
symptoms and treatment 
status. Consistently high scores on a particular domain may indicate 
significant 
and problematic areas for the individual 
that 
might 
warrant 
further assessment, 
treatment, and follow-up. Clinical judgment should always guide decision making. 


852 


Clinician-Rated Dimensions of Psychosis Symptom Severity 


Name:______________________________________ 
Age: __________ 
Date:________________ 


Instructions: Based on all the information you have on the individual and using your clinical judgment, please rate (with 


checkmark) the presence and severity of the following symptoms as experienced by the individual, when each symptom was 


at its most severe, in the past seven (7) days. 


Domain 
0 
1 
2 
3 
4 
Score 
I. Hallucinations 
. Not 
present 
. Equivocal (severity or 
duration not sufficient to be 
considered psychosis) 
. Present, but 
mild (little 
pressure to act 
upon voices or 
other types of 
hallucinations, 
not very 
. Present and 
moderate (some 
pressure to 
respond to 
voices or other 
types of 
hallucinations, 
. Present and 
severe (severe 
pressure to 
respond to voices 
or other types of 
hallucinations, or 
is very bothered 



bothered by 
hallucinations) 
or is somewhat 
bothered by 
hallucinations) 
by hallucinations) 
II. Delusions 
. Not 
present 
. Equivocal (severity or 
duration not sufficient to be 
considered psychosis) 
. Present, but 
mild (little 
pressure to act 
upon delusional 
beliefs, not very 
bothered by 
such beliefs) 
. Present and 
moderate (some 
pressure to act 
upon delusional 
beliefs, or is 
somewhat 
bothered by 
such beliefs) 
. Present and 
severe (severe 
pressure to act 
upon delusional 
beliefs, or is very 
bothered by such 
beliefs) 
III. Disorganized 
. Not 
. Equivocal (severity or 
. Present, but 
. Present and 
. Present and 
speech 
present 
duration not sufficient to be 
mild (some 
moderate 
severe (speech 
considered disorganization) 
difficulty 
(speech often 
almost impossible 
following 
difficult to 
to follow) 
speech) 
follow) 
IV. Abnormal 
. Not 
. Equivocal (severity or 
. Present, but 
. Present and 
. Present and 
psychomotor 
present 
duration not sufficient to be 
mild (occasional 
moderate 
severe (abnormal 
behavior 
considered abnormal 
abnormal or 
(frequent 
or bizarre motor 
psychomotor behavior) 
bizarre motor 
abnormal or 
behavior or 
behavior or 
bizarre motor 
catatonia almost 
catatonia) 
behavior or 
constant) 
catatonia) 
853 
V. Negative 
symptoms 
(restricted 
emotional 
expression or 
avolition) 
. Not 
present 
. Equivocal decrease in 
facial expressivity, 
prosody, gestures, or self-
initiated behavior 
. Present, but 
mild decrease in 
facial 
expressivity, 
prosody, 
gestures, or self-
initiated 
behavior 
. Present and 
moderate 
decrease in 
facial 
expressivity, 
prosody, 
gestures, or self-
initiated 
behavior 
. Present and 
severe decrease in 
facial expressivity, 
prosody, gestures, 
or self-initiated 
behavior 
VI. Impaired 
. Not 
. Equivocal (cognitive 
. Present, but 
. Present and 
. Present and 
cognition 
present 
function not clearly outside 
mild (some 
moderate (clear 
severe (severe 
the range expected for age 
reduction in 
reduction in 
reduction in 
or SES; i.e., within 0.5 SD 
cognitive 
cognitive 
cognitive 
of mean) 
function; below 
function; below 
function; below 
expected for age 
expected for age 
expected for age 
and SES, 0.5 1 
and SES, 1 2 
and SES, > 2 SD 
SD from mean) 
SD from mean) 
from mean) 
VII. Depression 
. Not 
present 
. Equivocal (occasionally 
feels sad, down, depressed, 
or hopeless; concerned 
about having failed 
someone or at something 
but not preoccupied) 
. Present, but 
mild (frequent 
periods of 
feeling very sad, 
down, 
moderately 
depressed, or 
hopeless; 
concerned about 
having failed 
someone or at 
something, with 
some 
preoccupation) 
. Present and 
moderate 
(frequent 
periods of deep 
depression or 
hopelessness; 
preoccupation 
with guilt, 
having done 
wrong) 
. Present and 
severe (deeply 
depressed or 
hopeless daily; 
delusional guilt or 
unreasonable self-
reproach grossly 
out of proportion 
to circumstances) 
VIII. Mania 
. Not 
present 
. Equivocal (occasional 
elevated, expansive, or 
irritable mood or some 
restlessness) 
. Present, but 
mild (frequent 
periods of 
somewhat 
elevated, 
expansive, or 
irritable mood 
or restlessness) 
. Present and 
moderate 
(frequent 
periods of 
extensively 
elevated, 
expansive, or 
irritable mood 
. Present and 
severe (daily and 
extensively 
elevated, 
expansive, or 
irritable mood or 
restlessness) 



or restlessness)or restlessness)
Note. SD = standard deviation; SES = socioeconomic status. 


854 


World Health Organization Disability Assessment 
Schedule 2.0 


The adult 
self-administered version of the World Health Organization Disability Assessment 
Schedule 2.0 (WHODAS 
2.0) is a 36-item 
measure that 
assesses disability in adults age 18 years 
and older. It 
has been validated across numerous cultures worldwide and demonstrated 
sensitivity to change. It 
assesses disability across six domains, including understanding and 
communicating, getting around, self-care, getting along with people, life activities (i.e., 
household, work, and/or school 
activities), and participation in society. If the adult 
individual 
is 
of impaired capacity and unable to complete the form 
(e.g., a patient 
with major neurocognitive 
disorder), a knowledgeable informant 
may complete the proxy-administered version of the 
measure, which is available at 
www.psychiatry.org/dsm5. Each item 
on the self-administered 
version of the WHODAS 
2.0 asks the individual 
to rate how much difficulty he or she has had in 
specific areas of functioning during the past 30 days. 


WHODAS 
2.0 Scoring Instructions Provided by WHO 


WHODAS 2.0 
summary 
scores. 
There are two basic options for computing the summary scores for 
the WHODAS 2.0 36-item full version. 


Simple: 
The scores assigned to each of the items  none  (1),  mild  (2),  moderate  (3), 
 severe  (4), and  extreme  (5) are summed for a maximum 
total 
raw score of 180. This 
method is referred to as simple scoring because the scores from 
each of the items are simply 
added up without 
recoding or collapsing of response categories; 
thus, there is no weighting of 
individual 
items. This approach is practical 
to use as a hand-scoring approach, and may be the 
method of choice in busy clinical 
settings or in paper-and-pencil 
interview situations. As a result, 
the simple sum 
of the scores of the items across all 
domains constitutes a statistic that 
is 
sufficient to describe the degree of functional limitations. 


Complex: 
The more complex method of scoring is called  item-response-theory  (IRT)  
based scoring. It 
takes into account 
multiple levels of difficulty for each WHODAS 
2.0 item. It 
takes the coding for each item 
response as  none,   mild,   moderate,   severe,  and  extreme  
separately, and then requires a computer to determine the summary score by differentially 
weighting the items and the levels of severity. The computer program 
is available from 
the WHO 
Web site. The scoring has three steps: 



Step 1 Summing of 
recoded item 
scores within each domain (i.e., for 
each item, the response options 1 5 are converted to 
a rate of 0 4, leading to a total raw score of 144). 



Step 2 Summing of all six domain scores. 
Step 3 Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability). 
WHODAS 2.0 
domain 
scores. 
WHODAS 
2.0 produces domain-specific scores for six different 
functioning domains: 
cognition, mobility, self-care, getting along, life activities (household and 



work/school), and participation. 
WHODAS 2.0 
population 
norms. 
For the population norms for IRT-based scoring of the WHODAS 


2.0 and for the population distribution of IRT-based scores for WHODAS 
2.0, please see 
www.who.int/classifications/icf/Pop_norms_distrib_IRT_scores.pdf. 
855 


Additional 
Scoring and Interpretation Guidance for DSM-5-TR Users 


The clinician is asked to review the individual s response on each item 
on the measure during the 
clinical 
interview and to indicate the self-reported score for each item 
in the section provided for 
 Clinician Use Only.  However, if the clinician determines that 
the score on an item 
should be 
different 
based on the clinical 
interview and other information available, he or she may indicate a 
corrected score in the raw item 
score box. Based on findings from 
the DSM-5 Field Trials in 
adult 
patient 
samples across six sites in the United States and one in Canada, DSM-5-TR 
recommends calculation and use of 
average scores for each domain and for general 
disability. 


The average scores are comparable to the WHODAS 
5-point 
scale, which allows the clinician to 
think of the individual s disability in terms of none (1), mild (2), moderate (3), severe (4), or 
extreme (5). The average domain and general 
disability scores were found to be reliable, easy to 
use, and clinically useful 
to the clinicians in the DSM-5 Field Trials. The average domain score 
is calculated by dividing the raw domain score by the number of items in the domain (e.g., if all 
the items within the  understanding and communicating  domain are rated as being moderate, 
then the average domain score would be 18/6 = 3, indicating moderate disability). The average 
general disability score 
is calculated by dividing the raw overall 
score by number of items in the 
measure (i.e., 36). The individual 
should be encouraged to complete all 
of the items on the 
WHODAS 
2.0. If no response is given on 10 or more items of the measure (i.e., more than 25% 
of the 36 total 
items), calculation of the simple and average general 
disability scores may not 
be 
helpful. If 10 or more of the total 
items on the measure are missing but 
the items for some of the 
domains are 75% 100% complete, the simple or average domain scores may be used for those 
domains. 


Frequency of Use 


To track change in the individual s level 
of disability over time, the measure may be completed 
at 
regular intervals as clinically indicated, depending on the stability of the individual s 
symptoms and treatment 
status. Consistently high scores on a particular domain may indicate 
significant 
and problematic areas for the individual 
that 
might 
warrant 
further assessment 
and 
intervention. 


856 



857 



858 



859 



Culture and Psychiatric Diagnosis 


This chapter 
provides basic information on integrating culture and social 
context 
in 
clinical 
diagnoses, with sections on key terms, cultural 
formulation, and cultural 
concepts of 
distress. 



The first section defines terms that are essential to the rest of the chapter: 
culture, race, and ethnicity. 
The Cultural 
Formulation section presents an outline for 
a systematic person-centered cultural 
assessment 
that 
is designed to 
be used by any clinician providing services to any individual 
in any care setting. This section also includes an interview 
protocol, the Cultural 
Formulation Interview, that 
operationalizes these components. Symptom 
presentations, interpretations 
of 
the illness or 
predicament 
that 
precipitates care, and help-seeking expectations are always influenced by individuals  
cultural 
backgrounds and sociocultural 
contexts. A person-centered cultural 
assessment 
can help improve the care of 
every 
individual, regardless of 
his or 
her 
background. Cultural 
formulation may be especially helpful 
for 
individuals who are 
affected by healthcare disparities driven by systemic disadvantage and discrimination. 
The Cultural 
Concepts of 
Distress section describes the ways individuals express, report, and interpret 
experiences of 
illness 
and distress. Cultural 
concepts of 
distress include idioms, explanations or 
perceived causes, and syndromes. Symptoms are 
expressed and communicated using cultural 
idioms of 
distress behaviors or 
linguistic terms, metaphors, phrases, or 
ways 
of 
talking about 
symptoms, problems, or 
suffering that 
are commonly used by individuals with similar 
cultural 
backgrounds 
to convey a wide range of 
concerns. Such idioms may be used for 
a broad spectrum 
of 
distress and may not 
indicate a 
psychiatric disorder. Common contemporary idioms in the United States include  burnout,   feeling stressed,   nervous 
breakdown,  and  feeling depressed,  in the sense of 
experiencing dissatisfaction or 
discouragement 
that 
does not 
meet 
criteria for 
any psychiatric disorder. Culturally specific explanations and syndromes are also common and distributed widely 
across populations. This section also provides some illustrative examples of 
idioms, explanations, and syndromes from 
diverse geographic regions. The examples were chosen because they have been well 
studied and their 
lack of 
familiarity to 
many U.S. clinicians highlights their specific verbal and behavioral expressions and communicative functions. 
Key Terms 


Understanding the cultural 
context 
of illness experience is essential 
for effective diagnostic 
assessment and clinical management. 


860 


Culture 
refers to systems of knowledge, concepts, values, norms, and practices that 
are 
learned and transmitted across generations. Culture includes language, religion and spirituality, 
family structures, life-cycle stages, ceremonial 
rituals, customs, and ways of understanding 
health and illness, as well 
as moral, political, economic, and legal 
systems. Cultures are open, 
dynamic systems that 
undergo continuous change over time; 
in the contemporary world, most 



individuals and groups are exposed to multiple cultural 
contexts, which they use to fashion their 
own identities and make sense of experience. This process of meaning-making derives from 
developmental 
and everyday social 
experiences in specific contexts, including health care, which 
may vary for each individual. Much of culture involves background knowledge, values, and 
assumptions that 
remain implicit 
or presumed and so may be difficult 
for individuals to describe. 
These features of culture make it 
crucial 
not 
to overgeneralize cultural 
information or stereotype 
groups in terms of fixed cultural 
traits. In relation to diagnosis, it 
is essential 
to recognize that 
all 
forms of illness and distress, including the DSM disorders, are shaped by cultural 
contexts. 
Culture influences how individuals fashion their identities, as well 
as how they interpret 
and 
respond to symptoms and illness. 


Race 
is a social, not 
a biological, construct 
that 
divides humanity into groups based on a 
variety of superficial 
physical 
traits such as skin color that 
have been falsely viewed as indicating 
attributes and capacities assumed to be inherent 
to the group. Racial 
categories and constructs 
have varied over history and across societies and have been used to justify systems of 
oppression, slavery, and genocide. The construct 
of race is important 
for psychiatry because it 
can lead to racial 
ideologies, racism, discrimination, and social 
oppression and exclusion, which 
have strong negative effects on mental 
health. There is evidence that 
racism 
can exacerbate many 
psychiatric disorders, contributing to poor outcome, and that 
racial 
biases can affect 
diagnostic 
assessment. 


Ethnicity 
is a culturally constructed group identity used to define peoples and communities. It 
may be rooted in a common history, ancestry, geography, language, religion, or other shared 
characteristics of a group, which distinguish that 
group from 
others. Ethnicity may be self-
assigned or attributed by outsiders. Increasing mobility, intermarriage, and intermixing of 
cultural 
groups have defined new mixed, multiple, or hybrid ethnic identities. These processes 
may also lead to the dilution of ethnic identification. 


Culture, race, and ethnicity may be related to political, economic, and social 
structural 
inequities associated with racism 
and discrimination resulting in health disparities. Cultural, 
ethnic, and racialized identities can be sources of strength and group support 
that 
enhance 
resilience. They may also lead to psychological, interpersonal, and intergenerational 
conflict 
or 
difficulties in adaptation that 
require socially and culturally informed diagnosis and clinical 
assessment. Additional 
key terms related to racialization and racism 
are defined in the DSM-5TR 
Section I Introduction, under  Cultural 
and Social 
Structural 
Issues,  in the subsection 
 Impact of Racism and Discrimination on Psychiatric Diagnosis.  


Cultural 
Formulation 


Outline for Cultural Formulation 


The Outline for Cultural 
Formulation introduced in DSM-IV provided a framework for assessing 
information about 
cultural 
features of an individual s mental 
health problem 
and how it 
relates to 
a social 
and cultural 
context 
and history. This assessment 
provides useful 
information on social 
context 
and illness experience relevant 
to the assessment 
of every individual, not 
only those 
whose cultural background may be unfamiliar to the clinician. 



861 


Updated from 
DSM-5, DSM-5-TR 
includes an expanded version of the Outline and an approach 
to assessment 
using the Cultural 
Formulation Interview (CFI), which has been field-tested 
among clinicians, patients, and accompanying relatives and found to be a feasible, acceptable, 
and useful cultural assessment tool. 


The Outline for Cultural 
Formulation calls for systematic assessment 
of the following 
categories: 



Cultural 
identity of 
the individual: 
Describe the individual s demographic (e.g., age, gender, ethnoracial 
background) 
or 
other 
socially and culturally defined characteristics that 
may influence interpersonal 
relationships, access to resources, and 
developmental 
and current 
challenges, conflicts, or 
predicaments. Other 
clinically relevant 
aspects of 
identity may include 
religious affiliation and spirituality, socioeconomic class, caste, personal 
and family places of 
birth and growing up, migrant 
status, occupation, and sexual 
orientation, among others. Note which aspects of 
identity are prioritized by the individual 
and 
how they interact 
(intersectionality), which may reflect 
the influence of 
clinical 
setting and health concerns. For 
migrants, 
the degree and kinds of 
involvement 
with both the cultural 
contexts of 
origin and the new cultural 
contexts should be noted. 
Similarly, for 
individuals who identify with racialized and ethnic groups, the degree of 
interaction and identification with 
their 
own group and other 
segments of 
society should be noted. Language abilities, preferences, and patterns of 
use are 
relevant 
for 
identifying difficulties with access to care, social 
integration, and clinical 
communication or 
the need for 
an 
interpreter. 
Cultural 
concepts of 
distress: 
Describe the cultural 
constructs that 
influence how the individual 
experiences, understands, 
and communicates his or 
her 
symptoms or 
problems to others. These constructs include cultural 
idioms of 
distress, cultural 
explanations or 
perceived causes, and cultural 
syndromes. The level 
of 
severity and meaning of 
the distressing experiences 
should be assessed in relation to the norms of 
the individual s cultural 
background. Priority symptoms, perceived 
seriousness of 
the illness, the level 
of 
associated stigma, and anticipated outcomes are all 
relevant. Elicit 
the individual s and 
family s or 
friends  
help-seeking expectations and plans, as well 
as patterns of 
self-coping and their 
connection to the 
individual s cultural 
concepts of 
distress, including past 
help-seeking experiences. Assessment 
of 
coping and help-seeking 
patterns should consider the use of professional as well as traditional, alternative, or complementary sources of care. 
Psychosocial 
stressors and 
cultural 
features of 
vulnerability and 
resilience: 
Identify key stressors, challenges, and 
supports in the individual s social 
environment 
(which may include both local 
and distant 
events). These include social 
determinants of 
the individual s mental 
health such as access to resources (e.g., housing, transportation) 
and opportunities 
(e.g., education, employment); 
exposure to racism, discrimination, and systemic institutional 
stigmatization; 
and social 
marginalization or 
exclusion (structural 
violence). Also assess the role of 
religion, family, and other 
interpersonal 
relationships and social 
networks (e.g., friends, neighbors, coworkers, online forums or 
groups) 
in causing stress or 
providing emotional, instrumental, and informational 
support. Social 
stressors and social 
supports vary with social 
context, 
family structure, developmental 
tasks, and the cultural 
meaning of 
events. Levels of 
functioning, disability, and resilience 
should be assessed in light of the individual s cultural background. 
Cultural 
features of 
the relationship 
between 
the individual 
and 
the clinician, treatment 
team, and 
institution: 
Identify differences in cultural 
background, language, education, and social 
status among other 
aspects of 
identity between 
an individual 
and clinician (or 
the treatment 
team 
and institution) 
that 
may cause difficulties in communication and may 
influence diagnosis and treatment. Considering the ways that individuals 


862 


and clinicians are positioned socially and perceive each other 
in terms of 
social 
categories may influence the assessment 



process. Experiences of 
racism 
and discrimination in the larger 
society may impede establishing trust 
and safety in the 
clinical 
diagnostic encounter. Effects may include problems eliciting symptoms, misunderstanding of 
the cultural 
and 
clinical 
significance of 
symptoms and behaviors, and difficulty establishing or 
maintaining the rapport 
needed for 
accurate 
assessment and an effective clinical alliance. 



Overallcultural assessment: 
Summarize the implications of 
the components of 
the cultural 
formulation identified in earlier 
sections of 
the Outline for 
the differential 
diagnosis of 
mental 
disorders and other 
clinically relevant 
issues or 
problems, as 
well as appropriate management and treatment intervention. 
Cultural Formulation Interview (CFI) 


The Cultural 
Formulation Interview (CFI) is a set 
of protocols that 
clinicians may use to obtain 
information during a mental 
health assessment 
about 
the impact 
of culture on key aspects of an 
individual s clinical 
presentation and care. The CFI consists of three components: 
the core CFI, a 
set 
of 16 questions that 
can be used to obtain an initial 
assessment 
from 
any individual; 
an 
Informant 
version of the core CFI to obtain collateral 
information; 
and a set 
of Supplementary 
modules to expand the evaluation as needed. In the CFI, the term 
culture includes: 



The processes through which individuals assign meaning to experience, drawing from 
the values, orientations, knowledge, 
and practices of 
the diverse social 
groups (e.g., ethnic groups, faith groups, occupational 
groups, veterans  
groups) 
and 
communities in which they participate. 
Aspects of 
individuals  
background, developmental 
experiences, and current 
social 
contexts and position that 
affect 
their 
perspective, such as age, gender, social 
class, geographic origin, migration, language, religion, sexual 
orientation, disability, 
or ethnic or racialized background. 
The influence of 
family, friends, and other 
community members (particularly, the individual s social 
network) 
on the 
individual s illness experience. 
The cultural 
background of 
the health care providers and the values and assumptions embedded in the organization and 
practices of health care systems and institutions that may affect the clinical interaction. 
Cultural 
processes involve interactions of the individual 
with local 
and larger social 
contexts. 
A cultural 
assessment 
thus evaluates processes both within the individual 
and in the social 
world, 
assessing the context as much as the person. 


The CFI is a brief semistructured interview for systematically assessing cultural 
factors 
relevant 
to the care of any individual. The CFI focuses on the individual s experience and the 
social 
contexts of the clinical 
problem, symptoms, or concerns. The CFI follows a person-
centered approach to cultural 
assessment 
by eliciting information from 
the individual 
about 
his 
or her own views and those of others in his or her social 
network. This approach is designed to 
avoid stereotyping, in that 
each individual s cultural 
knowledge affects how he or she interprets 
illness experience and guides how he or she seeks help. Because the CFI concerns the 
individual s personal 
views, there are no right 
or wrong answers to these questions. The core CFI 
(and informant 
version) is included later in this chapter and is available online at 
www.psychiatry.org/dsm5; the Supplementary modules are also available online. 


863 


The core CFI (and informant 
version) is formatted as two text 
columns. The left-hand 



column contains the instructions for administering the CFI and describes the goals for each 
interview domain. The questions in the right-hand column illustrate how to explore these 
domains, but 
they are not 
meant 
to be exhaustive. Follow-up questions may be needed to clarify 
individuals  answers. Questions may be rephrased as needed. The CFI is intended as a guide to 
cultural 
assessment 
and should be used flexibly to maintain a natural 
flow of the interview and 
rapport with the individual. 


The CFI is best 
used in conjunction with demographic information obtained before the 
interview in order to tailor the CFI questions to address the individual s background and current 
situation. Specific demographic domains to be explored with the CFI will 
vary across individuals 
and settings. A comprehensive assessment 
may include place of birth, age, gender, ethnic or 
racialized background, marital 
status, family composition, education, language fluencies, sexual 
orientation, religious or spiritual 
affiliation, occupation, employment, income, and migration 
history. 


The CFI can be used in the initial 
assessment 
of individuals at 
any age, in any clinical 
setting, 
regardless of the cultural 
background of the individual 
or of the clinician. Individuals and 
clinicians who appear to share the same cultural 
background may nevertheless differ in ways that 
are relevant 
to care. The CFI may be used in its entirety, or components may be incorporated into 
a clinical 
evaluation as needed. The CFI may be especially helpful 
in clinical 
practice when any 
of the following occur: 



Difficulty in diagnostic assessment 
owing to significant 
differences in the cultural, religious, or 
socioeconomic backgrounds 
of clinician and the individual. 
Uncertainty about the fit between culturally distinctive symptoms and diagnostic criteria. 
Difficulty in judging illness severity or impairment. 
Divergent 
views of 
symptoms or 
expectations of 
care based on previous experience with other 
cultural 
systems of 
healing 
and health care. 
Disagreementbetween the individual and clinician on the course of care. 
Potentialmistrust of mainstream services and institutions by individuals with collective histories of trauma and oppression. 
Limited engagement in and adherence to treatment by the individual. 
The core CFI emphasizes four domains of assessment: 
Cultural 
Definition of the Problem 
(questions 1 3); 
Cultural 
Perceptions of Cause, Context, and Support 
(questions 4 10); 
Cultural 
Factors Affecting Self-Coping and Past 
Help Seeking (questions 11 13); 
and Cultural 
Factors 
Affecting Current 
Help Seeking (questions 14 16). Both the person-centered process of 
conducting the CFI and the information it 
elicits are intended to enhance the cultural 
validity of 
diagnostic assessment, facilitate treatment 
planning, and promote the individual s engagement 
and satisfaction. To achieve these goals, the clinician should integrate the information obtained 
from 
the CFI with all 
other available clinical 
material 
into a comprehensive clinical 
and 
contextual 
evaluation. An Informant 
version of the CFI can be used to collect 
collateral 
information on the CFI domains from family members or caregivers. 


Supplementary modules have been developed that 
expand on each domain of the core CFI 
and guide clinicians who wish to explore these domains in greater depth. Supplementary 
modules have also been developed for specific populations, such as children and adolescents, 
elderly individuals, caregivers, and immigrants and refugees. These supplementary modules are 



referenced in the core CFI under the pertinent 
subheadings and are available online at 
www.psychiatry.org/dsm5. 


864 


Core 
Cultural 
Formulation 
Interview 
(CFI) 


Supplementary modules used to expand each CFI subtopic are noted in parentheses. 


INSTRUCTIONS TO 
THE INTERVIEWER ARE 


GUIDE TO 
INTERVIEWER 
ITALICIZED. 


The following questions aim to clarify key aspects of the 
presenting clinical problem from the point of view of the 
individual and other members of the individual s social 
network (i.e., family, friends, or others involved in current 
problem). This includes the problem s meaning, potential 
sources of help, and expectations for services. 


INTRODUCTION FOR THE INDIVIDUAL: 


I would like to understand the problems that bring you here so 
that I can help you more effectively. I want to know about 
your experience and ideas. I will ask some questions about 
what is going on and how you are dealing with it. Please 
remember there are no right or wrong answers. 


CULTURAL 
DEFINITION OF 
THE PROBLEM 


CULTURAL DEFINITION 
OF 
THE PROBLEM 


(Explanatory Model, Level of Functioning) 


Elicit the individual s view of core problems and key concerns. 


Focus on the individual s own way of understanding the 
problem. 


Use the term, expression, or brief description elicited in 
question 1 to identify the problem in subsequent questions 
(e.g.,  your conflict with your son ). 


Ask how individual frames the problem for members of the 
social network. 


Focus on the aspects of the problem that matter most to the 
individual. 


1. What brings you here today? 
IF INDIVIDUAL GIVES FEW DETAILS OR ONLY 
MENTIONS SYMPTOMS OR A MEDICAL DIAGNOSIS, 
PROBE: 
People often understand their problems in their own way, 
which may be similar to or different from how doctors 
describe the problem. How would you describe your 
problem? 


2. Sometimes people have different ways of describing their 
problem to their family, friends, or others in their 
community. How would you describe your problem to them? 
3. What troubles you most about your problem? 
CULTURAL 
PERCEPTIONS OF 
CAUSE, 
CONTEXT, 
AND SUPPORT 


CAUSES 


(Explanatory Model, Social Network, Older Adults) 


This question indicates the meaning of the condition for the 
individual, which may be relevant for clinical care. 


Note that individuals may identify multiple causes, depending 
on the facet of the problem they are considering. 


Focus on the views of members of the individual s social 
network. These may be diverse and vary from the 
individual s. 


4. Why do you think this is happening to you? What do youthink are the causes of your [PROBLEM]? 
PROMPT FURTHER IF REQUIRED: 


Some people may explain their problem as the result of bad 
things that happen in their life, problems with others, a 
physical illness, a spiritual reason, or many other causes. 


5. What do others in your family, your friends, or others in your 
community think is causing your [PROBLEM]? 
865 


STRESSORS 
AND SUPPORTS 


(Social Network, Caregivers, Psychosocial Stressors, Religion and Spirituality, Immigrants and Refugees, Cultural Identity, 
Older Adults, Coping and Help Seeking) 
Elicit information on the individual s life context, focusing on 6. Are there any kinds of support that make your [PROBLEM] 
resources, social supports, and resilience. May also probe 
better, such as support from family, friends, or others? 



other supports (e.g., from co-workers, from participation in 


religion or spirituality). 


Focus on stressful aspects of the individual s environment. Can 7. Are there any kinds of stresses that make your [PROBLEM] 
also probe, e.g., relationship problems, difficulties at work or 
worse, such as difficulties with money, or family problems? 
school, or discrimination. 


ROLE 
OF CULTURAL IDENTITY 


(Cultural Identity, Psychosocial Stressors, Religion and Spirituality, Immigrants and Refugees, Older Adults, Children and 
Adolescents) 


Sometimes, aspects of people s background or identity can 
make their [PROBLEM] better or worse. By background or 
identity, I mean, for example, the communities you belong 
to, the languages you speak, where you or your family are 
from, your race or ethnic background, your gender or sexual 
orientation, or your faith or religion. 


Ask the individual to reflect on the most salient elements of his 8. For you, what are the most important aspects of your 
or her cultural identity. Use this information to tailor 
background or identity? 
questions 9 10 as needed. 


Elicit aspects of identity that make the problem better or worse. 9. Are there any aspects of your background or identity that 
make a difference to your [PROBLEM]? 


Probe as needed (e.g., clinical worsening as a result of 
discrimination due to migration status, race/ethnicity, or 
sexual orientation). 


Probe as needed (e.g., migration-related problems; conflict 
10. Are there any aspects of your background or identity that 
across generations or due to gender roles). 
are causing other concerns or difficulties for you? 


CULTURAL 
FACTORS AFFECTING 
SELF-COPING 
AND PAST 
HELP SEEKING 


SELF-COPING 


(Coping and Help Seeking, Religion and Spirituality, Older Adults, Caregivers, Psychosocial Stressors) 


Clarify self-coping for the problem. 
11. Sometimes people have various ways of dealing with 
problems like [PROBLEM]. What have you done on your 
own to cope with your [PROBLEM]? 


866 


PAST HELP SEEKING 


(Coping and Help Seeking, Religion and Spirituality, Older Adults, Caregivers, Psychosocial Stressors, Immigrants and 
Refugees, Social Network, Clinician-Patient Relationship) 


Elicit various sources of help (e.g., medical care, mental health 
12. Often, people look for help from many different sources, 
treatment, support groups, work-based counseling, folk 
including different kinds of doctors, helpers, or healers. In 
healing, religious or spiritual counseling, other forms of 
the past, what kinds of treatment, help, advice, or healing 


have you sought for your [PROBLEM]? 


traditional or alternative healing). 


Probe as needed (e.g.,  What other sources of help have you 
PROBE IF DOES NOT DESCRIBE USEFULNESS OF HELP 
used? ). 
RECEIVED: 


Clarify the individual s experience and regard for previous 
What types of help or treatment were most useful? Not useful? 
help. 


BARRIERS 


(Coping and Help Seeking, Religion and Spirituality, Older Adults, Psychosocial Stressors, Immigrants and Refugees, Social 
Network, Clinician-Patient Relationship) 


Clarify the role of social barriers to help seeking, access to 
13. Has anything prevented you from getting the help you 
care, and problems engaging in previous treatment. 
need? 
PROBE AS NEEDED: 


Probe details as needed (e.g.,  What got in the way? ). 


For example, money, work or family commitments, stigma or 
discrimination, or lack of services that understand your 



language or background? 


CULTURAL 
FACTORS AFFECTING 
CURRENT 
HELP SEEKING 


PREFERENCES 


(Social Network, Caregivers, Religion and Spirituality, Older Adults, Coping and Help Seeking) 


Clarify individual s current perceived needs and expectations 
Now let s talk some more about the help you need. 
of help, broadly defined. 


Probe if individual lists only one source of help (e.g.,  What 
14. What kinds of help do you think would be most useful to 
other kinds of help would be useful to you at this time? ). 
you at this time for your [PROBLEM]? 


Focus on the views of the social network regarding help 
15. Are there other kinds of help that your family, friends, or 
seeking. 
other people have suggested would be helpful for you now? 


867 


CLINICIAN-PATIENT RELATIONSHIP 


(Clinician-Patient Relationship, Older Adults) 


Elicit possible concerns about the clinic or the clinician-patient 
Sometimes doctors and patients misunderstand each other 
relationship, including perceived racism, language barriers, 
because they come from different backgrounds or have 
or cultural differences that may undermine goodwill, 
different expectations. 
communication, or care delivery. 


Probe details as needed (e.g.,  In what way? ). 
16. Have you been concerned about this and is there anything 
that we can do to provide you with the care you need? 


Address possible barriers to care or concerns about the clinic 
and the clinician-patient relationship raised previously. 


868 


Cultural Formulation Interview (CFI) Informant 
Version 


The CFI Informant 
Version collects collateral 
information from 
an informant 
who is 
knowledgeable about 
the clinical 
problems and life circumstances of the identified individual. 
This version can be used to supplement 
information obtained from 
the core CFI or can be used 
instead of the core CFI when the individual 
is unable to provide information (e.g., children or 
adolescents, individuals with florid psychosis, individuals with cognitive impairment). 


Cultural 
Formulation 
Interview 
(CFI) Informant Version 


INSTRUCTIONS TO 
THE INTERVIEWER ARE 


GUIDE TO 
INTERVIEWER 
ITALICIZED. 


The following questions aim to clarify key aspects of the 
INTRODUCTION FOR THE INFORMANT: 
presenting clinical problem from the informant s point of 


I would like to understand the problems that bring your family 
view. This includes the problem s meaning, potential sources 
member/friend here so that I can help you and him/her more 
of help, and expectations for services. 
effectively. I want to know about 
your experience and ideas. 
I will ask some questions about what is going on and how 
you and your family member/friend are dealing with it. There 
are no right or wrong answers. 


RELATIONSHIP WITH THE PATIENT 


Clarify the informant s relationship with the individual and/or 
1. How would you describe your relationship to [INDIVIDUAL 
the individual s family. 
OR TO FAMILY]? 
PROBE IF NOT CLEAR: 


How often do you see [INDIVIDUAL]? 



CULTURAL 
DEFINITION OF 
THE PROBLEM 


Elicit the informant s view of core problems and key concerns. 


Focus on the informant s way of understanding the individual s 
problem. 


Use the term, expression, or brief description elicited in 
question 1 to identify the problem in subsequent questions 
(e.g.,  her conflict with her son ). 


Ask how informant frames the problem for members of the 
social network. 


Focus on the aspects of the problem that matter most to the 
informant. 


2. What brings your family member/friend here today? 
IF INFORMANT GIVES FEW DETAILS OR ONLY 
MENTIONS SYMPTOMS OR A MEDICAL DIAGNOSIS, 
PROBE: 
People often understand problems in their own way, which 
may be similar or different from how doctors describe the 
problem. How would you describe [INDIVIDUAL S] 
problem? 


3. Sometimes people have different ways of describing the 
problem to family, friends, or others in their community. 
How would you describe [INDIVIDUAL S] problem to 
them? 
4. What troubles you most about [INDIVIDUAL S] problem? 
CULTURAL 
PERCEPTIONS OF 
CAUSE, 
CONTEXT, 
AND SUPPORT 


This question indicates the meaning of the condition for the 
informant, which may be relevant for clinical care. 


Note that informants may identify multiple causes depending 
on the facet of the problem they are considering. 


Focus on the views of members of the individual s social 
network. These may be diverse and vary from the 
informant s. 


869 


CAUSES

 5. Why do you think this is happening to [INDIVIDUAL]?
What do you think are the causes of his/her [PROBLEM]? 


PROMPT FURTHER IF REQUIRED: 


Some people may explain the problem as the result of bad 
things that happen in their life, problems with others, a 
physical illness, a spiritual reason, or many other causes.

 6. What do others in [INDIVIDUAL S] family, his/her 
friends, or others in the community think is causing 
[INDIVIDUAL S] [PROBLEM]? 


STRESSORS 
AND SUPPORTS 


Elicit information on the individual s life context, focusing on 7. Are there any kinds of supports that make his/her 
resources, social supports, and resilience. May also probe 
[PROBLEM] better, such as from family, friends, or others? 
other supports (e.g., from co-workers, from participation in 
religion or spirituality). 


Focus on stressful aspects of the individual s environment. Can 8. Are there any kinds of stresses that make his/her 
also probe, e.g., relationship problems, difficulties at work or 
[PROBLEM] worse, such as difficulties with money, or 
school, or discrimination. 
family problems? 


ROLE 
OF CULTURAL IDENTITY 


Ask the informant to reflect on the most salient elements of the 
individual s cultural identity. Use this information to tailor 
questions 10 11 as needed. 


Elicit aspects of identity that make the problem better or worse. 
Probe as needed (e.g., clinical worsening as a result of 
discrimination due to migration status, race/ethnicity, or 
sexual orientation). 


Sometimes, aspects of people s background or identity can 
make the [PROBLEM] better or worse. By background or 
identity, I mean, for example, the communities you belong 
to, the languages you speak, where you or your family are 
from, your race or ethnic background, your gender or sexual 
orientation, and your faith or religion.

 9. For you, what are the most important aspects of 
[INDIVIDUAL S] background or identity? 


10. Are there any aspects of [INDIVIDUAL S] background or 
identity that make a difference to his/her [PROBLEM]? 
Probe as needed (e.g., migration-related problems; conflict 
11. Are there any aspects of [INDIVIDUAL S] background or 
across generations or due to gender roles). 
identity that are causing other concerns or difficulties for 



him/her? 


CULTURAL 
FACTORS AFFECTING 
SELF-COPING 
AND PAST 
HELP SEEKING 


870 


SELF-COPING 


Clarify individual s self-coping for the problem. 
12. Sometimes people have various ways of dealing with 
problems like [PROBLEM]. What has [INDIVIDUAL] done 
on his/her own to cope with his/her [PROBLEM]? 


PAST HELP SEEKING 


Elicit various sources of help (e.g., medical care, mental health 
13. Often, people also look for help from many different 
treatment, support groups, work-based counseling, folk 
sources, including different kinds of doctors, helpers, or 
healing, religious or spiritual counseling, other alternative 
healers. In the past, what kinds of treatment, help, advice, or 


healing has [INDIVIDUAL] sought for his/her 


healing). 


[PROBLEM]? 


Probe as needed (e.g.,  What other sources of help has he/she 


PROBE IF DOES NOT DESCRIBE USEFULNESS OF 
used? ). 


HELP RECEIVED: 
Clarify the individual s experience and regard for previous 
What types of help or treatment were most useful? Not 
help. 
useful? 


BARRIERS 


Clarify the role of social barriers to help seeking, access to 
14. Has anything prevented [INDIVIDUAL] from getting the 
care, and problems engaging in previous treatment. 
help he/she needs? 


Probe details as needed (e.g.,  What got in the way? ). 
PROBE AS NEEDED: 


For example, money, work or family commitments, stigma 
or discrimination, or lack of services that understand his/her 
language or background? 


CULTURAL 
FACTORS AFFECTING 
CURRENT 
HELP SEEKING 


PREFERENCES 


Clarify individual s current perceived needs and expectations 
Now let s talk about the help [INDIVIDUAL] needs. 
of help, broadly defined, from the point of view of the 
informant. 


Probe if informant lists only one source of help (e.g.,  What 
15. What kinds of help would be most useful to him/her at this 
other kinds of help would be useful to [INDIVIDUAL] at this 
time for his/her [PROBLEM]? 
time? ). 


Focus on the views of the social network regarding help 
16. Are there other kinds of help that [INDIVIDUAL S] family, 
seeking. 
friends, or other people have suggested would be helpful for 
him/her now? 


871 


CLINICIAN-PATIENT RELATIONSHIP 


Elicit possible concerns about the clinic or the clinician-patient 
Sometimes doctors and patients misunderstand each other 
relationship, including perceived racism, language barriers, 
because they come from different backgrounds or have 
or cultural differences that may undermine goodwill, 
different expectations. 
communication, or care delivery. 


Probe details as needed (e.g.,  In what way? ). 
17. Have you been concerned about this, and is there anything 
that we can do to provide [INDIVIDUAL] with the care 


Address possible barriers to care or concerns about the clinic 


he/she needs? 


and the clinician-patient relationship raised previously. 



Cultural 
Concepts of Distress 


Relevance for Diagnostic Assessment 


The term 
cultural concepts of distress 
refers to ways that 
individuals experience, understand, and 
communicate suffering, behavioral 
problems, or troubling thoughts and emotions. Three main 
types of cultural 
concepts of distress may be distinguished. Cultural 
idioms of 
distress 
are ways 
of expressing distress that 
may not 
involve specific symptoms or syndromes, but 
that 
provide 
collective, shared ways of experiencing and talking about 
personal 
or social 
concerns. For 
example, everyday talk about 
 nerves  or  depression  may refer to widely varying forms of 
suffering without 
mapping onto a discrete set 
of symptoms, syndrome, or disorder. Cultural 
explanations 
or perceived causes are labels, attributions, or features of an explanatory model 
that 
indicate culturally recognized meaning or etiology for symptoms, illness, or distress. Cultural 
syndromes 
are clusters of symptoms and attributions that 
tend to co-occur among individuals in 
specific cultural 
groups, communities, or contexts and that 
are recognized locally as coherent 
patterns of experience. 


These three cultural 
concepts of distress cultural 
idioms of distress, cultural 
explanations, 
and cultural 
syndromes are more relevant 
to clinical 
practice than the older formulation 
culture-bound syndrome. Specifically, the term 
culture-bound syndrome 
ignores the fact 
that 
clinically important 
cultural 
differences often involve explanations or experience of distress 
rather than culturally distinctive configurations of symptoms. Furthermore, the term 
culture 
bound 
overemphasizes the extent 
to which cultural 
concepts of distress are characterized by 
highly idiosyncratic experiences that 
are restricted to specific geographic regions. The current 
formulation acknowledges that 
all 
forms of distress are locally shaped, including the DSM 
disorders. From 
this perspective, many DSM diagnoses can be understood as operationalized 
prototypes that 
started out 
as cultural 
syndromes and became widely accepted as a result 
of their 
clinical 
and research utility. Across groups there remain culturally patterned differences in 
symptoms, ways of talking about 
distress, and locally perceived causes, which in turn are 
associated with coping strategies and patterns of help seeking. 


Cultural 
concepts of distress arise from 
local 
 folk  or professional 
diagnostic systems for 
mental and emotional distress, and they may also reflect the influence of 


872 


biomedical 
concepts. Cultural 
concepts of distress have four key features in relation to the 
DSM-5 nosology: 



There is seldom 
a one-to-one correspondence of 
any cultural 
concept 
of 
distress with a DSM diagnostic entity; 
the 
correspondence is more likely to be one-to-many in either 
direction. Symptoms or 
behaviors that 
might 
be sorted by DSM-5 
into several 
disorders may be included in a single cultural 
concept 
of 
distress, and diverse presentations that 
might 
be 
classified by DSM-5 as variants of 
a single disorder 
may be sorted into several 
distinct 
concepts by an indigenous diagnostic 
system. 
Cultural 
concepts of 
distress may apply to a wide range of 
symptom 
and functional 
severity, including presentations that 
do 
not 
meet 
DSM criteria for 
any mental 
disorder. For 
example, an individual 
with acute grief 
or 
a social 
predicament 
may use 

the same idiom of distress or display the same cultural syndrome as another individual with more severe psychopathology. 



In common usage, the same cultural 
term 
frequently denotes more than one type of 
cultural 
concept 
of 
distress. A familiar 
example may be the concept 
of 
 depression,  which may be used to describe a syndrome (e.g., major 
depressive disorder), 
an idiom 
of 
distress (e.g., as in the common expression  I 
feel 
depressed ), or 
an explanation or 
perceived cause (e.g.,  the 
baby was born with emotional problems because his mother suffered from depression during her pregnancy ). 
Like culture and DSM itself, cultural 
concepts of 
distress may change over 
time in response to both local 
and global 
influences. 
Cultural concepts of distress are important to psychiatric diagnosis for several reasons: 



To enhance identification 
of 
individuals  
concerns and 
detection 
of 
psychopathology: 
Referring to cultural 
concepts of 
distress in screening instruments or 
in reviews of 
systems may facilitate identification of 
individuals  
concerns and enhance 
detection of 
psychopathology, as individuals may be more familiar 
with these cultural 
concepts of 
distress than with 
professional terminology. 
To avoid 
misdiagnosis: 
Cultural 
variation in symptoms and in explanatory models associated with these cultural 
concepts 
of 
distress may lead clinicians to misjudge the severity of 
a problem 
or 
assign the wrong diagnosis (e.g., socially warranted 
suspicion may be misunderstood as paranoia; unfamiliar symptom presentations may be misdiagnosed as psychosis). 
To obtain 
useful 
clinical 
information: 
Cultural 
variations in symptoms and attributions may be associated with particular 
features of 
risk, resilience, and outcome. Clinical 
exploration of 
cultural 
concepts of 
distress can elicit 
information on the 
role that specific contexts play in symptom development and course and in their response to coping strategies. 
To improve clinical 
rapport 
and 
engagement: 
 Speaking the language of 
the patient,  both linguistically and in terms of 
his or 
her 
dominant 
cultural 
concepts of 
distress and metaphors, can result 
in greater 
communication and satisfaction, 
facilitate treatment negotiation, and lead to higher retention and adherence. 
To improve therapeutic efficacy: 
Culture influences the psychological 
mechanisms of 
a disorder, which need to be 
understood and addressed to improve clinical 
efficacy. For 
example, culturally specific catastrophic cognitions can 
contribute to symptom escalation into panic attacks. 
To guide clinical 
research: 
Locally perceived connections between cultural 
concepts of 
distress may help identify patterns 
of 
comorbidity and underlying biological 
substrates. Cultural 
concepts of 
distress, particularly cultural 
syndromes, may also 
point to previously unrecognized disorders or variants that could be included in future 
873 


nosological 
revisions (e.g., in a change from 
DSM-IV, the concept 
of 
possession was added to the DSM-5 criteria for 
dissociative identity disorder). 



To clarify cultural 
epidemiology: 
Cultural 
concepts of 
distress are not 
endorsed uniformly by everyone in a given cultural 
context. Distinguishing cultural 
idioms of 
distress, cultural 
explanations, and cultural 
syndromes provides an approach for 
studying the distribution of 
cultural 
features of 
illness across settings and regions, and over 
time. It 
also suggests questions 
about 
cultural 
determinants of 
risk, course, and outcome in clinical 
and community settings to enhance the evidence base of 
cultural research. 
DSM-5 includes information on cultural 
concepts of distress in order to improve the accuracy 
of diagnosis and the comprehensiveness of clinical 
assessment. Clinical 
assessment 
of 
individuals presenting with these cultural 
concepts of distress should determine whether their 
presentation meets DSM-5 criteria for a specified disorder or instead is best 
classified as an other 



specified 
diagnosis. Once the disorder is diagnosed, the cultural 
terms and explanations should 
be included in case formulations; 
they may help clarify symptoms and etiological 
attributions 
that 
could otherwise be confusing. Individuals whose symptoms do not 
meet 
DSM criteria for a 
specific mental 
disorder may still 
expect 
and require treatment; 
this should be assessed on a caseby-
case basis. In addition to the CFI and its informant 
and supplementary modules, DSM-5-TR 
contains the following information and tools that 
may be useful 
when integrating cultural 
information in clinical practice: 



Data in 
updated 
DSM-5-TR text 
for specific disorders: 
The text 
includes information on cultural 
variations in symptom 
expression; 
attributions for 
disorder 
causes or 
precipitants; 
factors associated with differential 
prevalence across 
demographic groups; 
cultural 
norms that 
may affect 
the threshold for 
pathology and the perceived severity of 
the condition; 
risk for 
misdiagnosis when evaluating individuals from 
socially oppressed ethnoracial 
or 
marginalized groups; 
associated 
cultural 
concepts of 
distress; 
and other 
material 
relevant 
to culturally informed diagnosis. It 
is important 
to emphasize that 
there is no one-to-one correspondence at 
the categorical 
level 
between DSM disorders and cultural 
concepts of 
distress. 
Differential 
diagnosis for 
individuals must 
therefore incorporate information on cultural 
variation with information elicited 
by the CFI. 
Other Conditions That 
May Be a Focus of 
Clinical 
Attention: 
Some of 
the clinical 
concerns identified by the CFI 
may 
correspond to one of 
the conditions or 
problems listed in the Section II 
chapter 
 Other 
Conditions That 
May Be a Focus of 
Clinical 
Attention  (e.g., acculturation problems, parent-child relational 
problems, religious or 
spiritual 
problems), along 
with the associated ICD-10-CM code. 
Examples of 
Cultural Concepts of 
Distress 


Clinicians need to familiarize themselves with individuals  cultural 
concepts of distress to 
understand individuals  concerns and facilitate accurate diagnostic assessment; 
use of the 
Cultural 
Formulation Interview may help in this regard. The following ten examples were 
selected to illustrate some of the ways in which cultural 
concepts of distress may affect 
the 
process of diagnosis. The principles illustrated with these examples can be applied to the myriad 
other cultural concepts of distress found in specific cultural contexts. 


The same term 
may be used for multiple types of cultural 
concepts of distress and clinical 
presentations, depending on context. Potentially, cultural 
concepts of distress can occur on their 
own or coexist 
with any psychiatric disorder and influence clinical 
presentation, course, and 
outcome. For example, in U.S. Latinx communities, ataque de nervios 
can be comorbid with 
nearly all psychiatric disorders. 


Each of the following examples of cultural 
concepts of distress includes a description of 
 Related conditions in DSM-5-TR  to highlight 1) the DSM-5 disorders that overlap 


874 


phenomenologically with the cultural 
concept 
of distress (e.g., panic disorder and ataque de 
nervios, due to their paroxysmic nature and symptom 
similarity) and 2) the DSM-5 disorders that 
are frequently attributed to the causal explanation or idiom (e.g., PTSD and kufungisisa). 


Ataque de nervios 


Ataque de nervios 
( attack of nerves ) is a syndrome found in Latinx cultural 
contexts, 



characterized by symptoms of intense emotional 
upset, including acute anxiety, anger, or grief; 
screaming and shouting uncontrollably; 
attacks of crying; 
trembling; 
heat 
in the chest 
rising into 
the head; 
and becoming verbally and physically aggressive. Dissociative experiences (e.g., 
depersonalization, derealization, amnesia), seizure-like or fainting episodes, and suicidal 
behavior are prominent 
in some ataques 
but 
absent 
in others. A general 
feature of an ataque de 
nervios 
is a sense of being out 
of control. Attacks frequently occur as a direct 
result 
of a stressful 
event 
relating to the family, such as news of the death of a close relative, conflicts with a spouse 
or children, or witnessing an accident 
involving a family member. For a minority of individuals, 
no particular social 
or interpersonal 
event 
triggers their ataques; 
instead, their vulnerability to 
losing control comes from the accumulated experience of suffering. 


No one-to-one relationship has been found between ataque 
and any specific psychiatric 
disorder, although several 
disorders, including panic disorder, other specified or unspecified 
dissociative disorder, and functional 
neurological 
symptom 
disorder (conversion disorder), have 
symptomatic overlap with ataque. 


In community samples, ataque 
is reported among U.S. Latinx by 7% 15% of adults and 4%  
9% of youth, depending on region and Latinx subgroup. It 
is associated with suicidal 
thoughts, 
disability, and outpatient 
psychiatric utilization, after adjustment 
for psychiatric diagnoses, 
traumatic exposure, and other covariates. However, some ataques 
represent 
normative 
expressions of acute distress (e.g., at 
a funeral) without 
clinical 
sequelae. The term 
ataque de 
nervios 
may also refer to an idiom 
of distress that 
includes any  fit -like paroxysm 
of 
emotionality (e.g., hysterical 
laughing) and may be used to indicate an episode of loss of control 
in response to an intense stressor. 


Related 
conditions 
in 
other cultural 
contexts. 
Indisposition in Haiti, blacking out 
in several 
West 
Indies and Caribbean countries, and falling out 
in the Southern United States. This use of the 
terms blacking out or falling out should not be confused with alcohol- or other substance-induced 
blackouts or amnesia. 


Related 
conditions 
in 
DSM-5-TR. 
Panic attack, panic disorder, other specified or unspecified 
dissociative disorder, functional 
neurological 
symptom 
disorder, intermittent 
explosive disorder, 
other specified or unspecified anxiety disorder, other specified or unspecified trauma- and 
stressor-related disorder. 


Dhat syndrome 


Dhat 
syndrome 
is a term 
that 
was coined in South Asia little more than half a century ago to 
account 
for common clinical 
presentations of young men who attributed their various symptoms 
to semen loss. Despite the name, it 
is not 
a discrete syndrome but 
rather a cultural 
explanation of 
distress for individuals who refer to diverse symptoms, such as anxiety, fatigue, weakness, 
weight 
loss, erectile dysfunction, other multiple somatic complaints, and depressed mood. The 
cardinal 
feature is anxiety and distress about 
the loss of dhat 
in the absence of any identifiable 
physiological 
dysfunction. Dhat 
was identified by individuals as a white discharge that 
was 
noted on defecation or urination. Ideas about 
this substance are related to the concept 
of dhatu 
(semen) described in the Hindu system 
of medicine, Ayurveda, as one of seven essential 
bodily 
fluids whose balance is necessary to maintain health. 


875 



Although dhat 
syndrome 
was formulated as a clinical 
category to help inform 
local 
clinical 
practice, related ideas about 
the harmful 
effects of semen loss have been shown to be widespread 
in the general 
population, suggesting a cultural 
disposition for explaining health problems and 
symptoms with reference to dhat-related concepts. Research in health care settings has yielded 
diverse estimates of the prevalence of dhat 
syndrome 
(e.g., 64% of men attending psychiatric 
clinics in India for sexual 
complaints; 
30% of men attending general 
medical 
clinics in Pakistan). 
Although dhat 
syndrome 
is most 
commonly identified with young men from 
lower 
socioeconomic backgrounds, middle-age men may also be affected. Comparable concerns about 
white vaginal 
discharge (leukorrhea) have been associated with a variant 
of the concept 
for 
women. The term 
dhat 
may also be used as an idiom 
and causal 
explanation for sexually 
transmitted infections (e.g., gonorrhea, chlamydia), in the absence of psychological distress. 


Related 
conditions 
in 
other cultural 
contexts. 
Koro 
in Southeast 
Asia, particularly Singapore, and 


shen-k uei ( kidney deficiency ) in China. 
Related 
conditions 
in 
DSM-5-TR. 
Major depressive disorder, persistent 
depressive disorder, 
generalized anxiety disorder, somatic symptom 
disorder, illness anxiety disorder, erectile 
disorder, early (premature) ejaculation, other specified or unspecified sexual 
dysfunction, 
educational problems. 


Hikikomori 


Hikikomori 
(a Japanese term 
composed of hiku 
[to pull 
back] and moru 
[to seclude oneself]) is a 
syndrome of protracted and severe social 
withdrawal 
observed in Japan that 
may result 
in 
complete cessation of in-person interactions with others. The typical 
picture in hikikomori 
is an 
adolescent 
or young adult 
male who does not 
leave his room 
within his parents  home and has no 
in-person social 
interactions. This behavior may initially be ego-syntonic but 
usually leads to 
distress over time; 
it 
is often associated with high intensity of Internet 
use and virtual 
social 
exchanges. Other features include no interest 
or willingness to attend school 
or work. The 2010 
guideline of the Japan Ministry of Health, Labor, and Welfare requires 6 months of social 
withdrawal 
for a diagnosis of hikikomori. The extreme social 
withdrawal 
seen in hikikomori may 
occur in the context 
of an established DSM-5 disorder ( secondary ) or manifest 
independently 
( primary ). 


Related 
conditions 
in 
other cultural 
contexts. 
Protracted social 
withdrawal 
among adolescents and 
young adults has been reported in many settings, including Australia, Bangladesh, Brazil, China, 
France, India, Iran, Italy, Oman, South Korea, Spain, Taiwan, Thailand, and the United States. 
Individuals with hikikomori-type behaviors in Japan, India, South Korea, and the United States 
tend to display high levels of loneliness, limited social 
networks, and moderate functional 
impairment. 


Related 
conditions 
in 
DSM-5-TR. 
Social 
anxiety disorder, major depressive disorder, generalized 
anxiety disorder, posttraumatic stress disorder, autism 
spectrum 
disorder, schizoid personality 
disorder, avoidant 
personality disorder, schizophrenia or other psychotic disorder. The condition 
may also be associated with Internet gaming disorder and, in adolescents, with school refusal. 


Khy l 
cap 


 Khy l 
attacks  (khy l 
cap), or  wind attacks,  is a syndrome found in Cambodian cultural 



contexts. Common symptoms include those of panic attacks, such as dizziness, palpitations, 
shortness of breath, and cold extremities, as well 
as other symptoms of anxiety and autonomic 
arousal 
(e.g., tinnitus and neck soreness). Khy l 
attacks include catastrophic cognitions centered 
on the concern that 
khy l 
(a windlike substance) may rise in the body along with blood and 
cause a range of serious effects (e.g., compressing the lungs to cause 


876 


shortness of breath and asphyxia; 
entering the cranium 
to cause tinnitus, dizziness, blurry vision, 
and a fatal 
syncope). Khy l 
attacks may occur without 
warning but 
are frequently brought 
about 
by triggers such as worrisome thoughts, standing up (i.e., orthostasis), specific odors with 
negative associations, and agoraphobic-type cues like going to crowded spaces or riding in a car. 
Khy l 
attacks usually meet 
panic attack criteria and may shape the experience of other anxiety 
and trauma- and stressor-related disorders. Khy l 
attacks may be associated with considerable 
disability. 


Related 
conditions 
in 
other cultural 
contexts. 
Pen lom in Laos, srog rlung gi 
nad 
in Tibet, vata 
in Sri 


Lanka, and hwa byung in Korea. 
Related 
conditions 
in 
DSM-5-TR. 
Panic attack, panic disorder, generalized anxiety disorder, 
agoraphobia, posttraumatic stress disorder, illness anxiety disorder. 


Kufungisisa 


Kufungisisa 
( thinking too much  in Shona) is an idiom 
of distress and a cultural 
explanation 
among the Shona of Zimbabwe. As an explanation, it 
is considered to be causative of anxiety, 
depression, and somatic problems (e.g.,  My heart 
is painful 
because I think too much ). As an 
idiom of psychosocial distress, it is indicative of interpersonal and social difficulties (e.g., marital 
problems, having no money to take care of children, unemployment). Kufungisisa 
involves 
ruminating on upsetting thoughts, particularly worries, including concerns about chronic physical 
illness, such as HIV-related disorders. 


Kufungisisa 
is associated with a range of psychopathology, including anxiety symptoms, 
excessive worry, panic attacks, depressive symptoms, irritability, and posttraumatic stress 
disorder. In a study of a random 
community sample, two-thirds of the cases identified by a 
general psychopathology measure included this complaint. 


Related 
conditions 
in 
other cultural 
contexts. 
 Thinking too much  is a common idiom 
of distress 
and cultural 
explanation across many countries and ethnic groups; 
despite some commonalities 
across global 
regions,  thinking too much  shows important 
heterogeneity across and within 
cultural 
contexts. It 
has been described in Africa, Asia, the Caribbean and Latin America, the 
Middle East, and among indigenous groups.  Thinking too much  may also be a key component 
of cultural 
syndromes such as  brain fag  in Nigeria. In the case of  brain fag,   thinking too 
much  is primarily attributed to excessive study, which is considered to damage the brain in 
particular, with symptoms including feelings of heat or crawling sensations in the head. 


Cross-culturally,  thinking too much  typically references ruminative, intrusive, and/or 
anxious thoughts sometimes focused on a singular concern or past 
trauma and other times 
based on numerous current 
worries. In some contexts, it 
is thought 
to lead to more severe 
disorder-like psychosis, suicidal thoughts, or even death. 



Related 
conditions 
in 
DSM-5-TR. 
Major depressive disorder, persistent 
depressive disorder, 
generalized anxiety disorder, posttraumatic stress disorder, obsessive-compulsive disorder, 
prolonged grief disorder. 


Maladi 
dyab 


Maladi dyab or maladi satan 
(literally  devil/Satan illness,  also referred to as  sent 
sickness ) is 
a cultural 
explanation in Haitian communities for diverse medical 
and psychiatric disorders, or 
other negative experiences and problems in functioning. In this explanatory model, interpersonal 
envy and malice cause people to harm 
their enemies by having sorcerers send illnesses such as 
psychosis, depression, social 
or academic failure, and inability to perform 
activities of daily 
living. These sicknesses have various names (e.g., ekspedisyon, m v  zespri, kout poud) based on 
how they are  sent . This etiological 
explanation assumes that 
illness may be caused by others  
envy and hatred, provoked by the 


877 


victim s economic success as evidenced by a new job or expensive purchase. One person s gain 
is assumed to produce another person s loss, so visible success makes an individual 
vulnerable to 
attack. Assigning the label 
of  sent 
sickness  depends more on mode of onset, social 
status, and 
form 
of treatment 
that 
proves successful 
than on presenting symptoms. A wide range of 
psychiatric disorders can be attributed to this cultural 
explanation. The acute onset 
of new 
symptoms or an abrupt 
behavioral 
change raises suspicions of a spiritual 
attack. An individual 
who is attractive, intelligent, or wealthy is perceived as especially vulnerable, and even young 
healthy children are at risk. 


Related 
conditions 
in 
other cultural 
contexts. 
Concerns about 
illness (typically, physical 
illness) 
caused by envy or social 
conflict 
are common across cultural 
contexts and often expressed in the 
form of  evil eye  (e.g., in Spanish, mal de ojo; in Italian, mal occhiu). 


Related 
conditions 
in 
DSM-5-TR. 
Subsyndromal 
affliction (e.g., problems related to the social 
environment, educational 
problems), in addition to a wide range of psychiatric disorders; 
the 
cultural 
explanation of supernatural 
forces may lead to misdiagnosis of delusional 
disorder, 
persecutory type; or schizophrenia. 


Nervios 


Nervios 
( nerves ) is a common cultural 
idiom 
of distress and causal 
explanation in Latinx 
cultural 
contexts in the United States and Latin America. Nervios 
refers to a general 
state of 
vulnerability to stressful 
life experiences and to difficult 
life circumstances. The term 
nervios 
includes a wide range of symptoms of emotional 
distress, somatic disturbance, and inability to 
function. The most 
common symptoms attributed to nervios 
include headaches and  brain aches  
(occipital 
neck tension), irritability, gastrointestinal 
disturbances, sleep difficulties, nervousness, 
easy tearfulness, inability to concentrate, trembling, tingling sensations, and mareos 
(dizziness 
with occasional 
vertigo-like exacerbations). Nervios 
is a broad cultural 
idiom 
of distress that 
spans the range of severity from 
cases with no mental 
disorder to presentations resembling 
adjustment, anxiety, depressive, dissociative, somatic symptom, 
or psychotic disorders. The term 
can also refer to a cultural 
explanation for multiple forms of psychological 
distress, especially 



those involving weakness, enervation, and anxiety. Nervios 
may indicate a range of conditions, 
which show regional 
variation, related to the nervous system 
(literally, the anatomical 
nerves). In 
Puerto Rican communities, for example, nervios 
includes conditions such as  being nervous 
since childhood,  which appears to be more of a trait 
and may precede social 
anxiety disorder, 
and  being ill 
with nerves,  which is more related than other forms of nervios 
to psychiatric 
problems, especially dissociation and depression. 


Related 
conditions 
in 
other cultural 
contexts. 
Nevra 
among Greeks in North America, nierbi 
among 
Sicilians in North America, and  nerves  among Whites in Appalachia and Newfoundland. 
 Tension  is a related idiom and causal explanation among South Asian popul ations. 


Related 
conditions 
in 
DSM-5-TR. 
Major depressive disorder, persistent 
depressive disorder, 
generalized anxiety disorder, social 
anxiety disorder, other specified or unspecified dissociative 
disorder, somatic symptom disorder, schizophrenia. 


Shenjing shuairuo 


Shenjing shuairuo 
( weakness of the nervous system  in Mandarin Chinese) is a cultural 
syndrome that 
integrates conceptual 
categories of Traditional 
Chinese Medicine with the 
Western construct 
of neurasthenia. In the second, revised edition of the Chinese Classification of 
Mental 
Disorders 
(CCMD-2-R), shenjing shuairuo 
was defined as a syndrome composed of 
three out 
of five symptom 
clusters: 
weakness (e.g., mental 
fatigue), emotions (e.g., feeling 
vexed), excitement (e.g., increased recollections), nervous pain (e.g., headache), 


878 


and sleep (e.g., insomnia). Fan nao 
(feeling vexed) is a form 
of irritability mixed with worry and 
distress over conflicting thoughts and unfulfilled desires. The third edition of the CCMD retained 
shenjing shuairuo 
as a somatoform 
diagnosis of exclusion. However, China adopted the ICD-10 
as its official 
classification system 
in 2011, displacing the CCMD; 
although ICD-10 included 
neurasthenia as a diagnostic category, ICD-11 does not. The use of shenjing shuairuo 
has 
decreased substantially in recent 
years and appears to have been replaced by idioms of 
depression and anxiety, at 
least 
in urban areas; 
among mental 
health clinicians, shenjing 
shuairuo 
may largely be invoked in interactions with traditional 
patients to facilitate 
communication and limit the stigma associated with psychiatric diagnoses. 


Salient precipitants of shenjing shuairuo 
include work or family-related stressors, loss of face 
(mianzi, lianzi), and an acute sense of failure (e.g., in academic performance). Shenjing shuairuo 
is related to traditional 
concepts of weakness (xu) and health imbalances related to deficiencies 
of a vital 
essence (e.g., the depletion of qi 
[vital 
energy] following overstraining or stagnation of 
qi 
due to excessive worry). In the traditional 
interpretation, shenjing shuairuo 
results when 
bodily channels (jing) conveying vital 
forces (shen) become dysregulated as a result 
of various 
social 
and interpersonal 
stressors, such as the inability to change a chronically frustrating and 
distressing situation. Various psychiatric disorders are associated with shenjing shuairuo, notably 
mood, anxiety, and somatic symptom 
disorders. In medical 
clinics in China, however, up to 45% 
of patients with shenjing shuairuo 
do not 
have symptoms that 
meet 
criteria for any DSM-IV 
disorder. 



879 


Related 
conditions 
in 
other cultural 
contexts. 
Neurasthenia-spectrum 
idioms and syndromes are 
present 
in many cultural 
contexts, including India (ashaktapanna), Mongolia (yadargaa), and 


Japan (shinkei-suijaku), among other settings. Other conditions, such as brain fag syndrome, 
burnout syndrome, and chronic fatigue syndrome, are also closely related. 
Related 
conditions 
in 
DSM-5-TR. 
Major depressive disorder, persistent 
depressive disorder, 


generalized anxiety disorder, somatic symptom 
disorder, social 
anxiety disorder, specific phobia, 
posttraumatic stress disorder. 


Susto 


Susto 
( fright ) is a cultural 
explanation for distress and misfortune prevalent 
in some Latinx 
cultural 
contexts in North, Central, and South America. It 
is not 
recognized as an illness category 
among Latinx from 
the Caribbean. Susto 
is an illness attributed to a frightening event 
that 
causes 
the soul 
to leave the body and results in unhappiness and sickness, as well 
as difficulties 
functioning in key social 
roles. Symptoms may appear any time from 
days to years after the 
fright 
is experienced. In extreme cases, susto 
may result 
in death. There are no specific defining 
symptoms for susto; however, symptoms that are often reported by individuals with susto include 
appetite disturbances; 
inadequate or excessive sleep; 
troubled sleep or dreams; 
feelings of 
sadness, low self-worth, or dirtiness; 
interpersonal 
sensitivity; 
and lack of motivation to do 
anything. Somatic symptoms accompanying susto 
may include muscle aches and pains, cold in 
the extremities, pallor, headache, stomachache, and diarrhea. Precipitating events are diverse and 
include natural 
phenomena, animals, interpersonal 
situations, and supernatural 
agents, among 
others. 


Three syndromic types of susto 
(referred to as cibih 
in the Zapotec language) have been 
identified, each having different 
relationships with psychiatric diagnoses. An interpersonal 
susto 
characterized by feelings of loss, abandonment, and not 
being loved by family, with 
accompanying symptoms of sadness, poor self-image, and suicidal 
thoughts, seems to be closely 
related to major depressive disorder. When susto 
results from 
a traumatic event 
that 
plays a 
major role in shaping symptoms and in emotional 
processing of the experience, the diagnosis of 
posttraumatic stress disorder appears more appropriate. Susto 
characterized by various recurrent 
somatic symptoms for which the individual 
seeks health care from 
several 
practitioners is 
thought to resemble a somatic symptom disorder. 
Related 
conditions 
in 
other cultural 
contexts. 
Similar etiological 
concepts and symptom 


configurations are found globally. In the Andean region, susto 
is referred to as espanto. Soul 
loss 
conditions in South Asia and Southeast 
Asia also share features with susto. In soul 
loss, 
individuals experiencing a fright 
are thought 
to temporarily lose their soul, a piece of their soul, 
or one of many souls. This makes the individual 
vulnerable to other physical 
and psychological 
forms of distress. 


Related 
conditions 
in 
DSM-5-TR. 
Major depressive disorder, posttraumatic stress disorder, other 
specified or unspecified trauma and stressor-related disorder, somatic symptom disorder. 


Taijin kyofusho 



Taijin kyofusho 
( interpersonal 
fear disorder  in Japanese) is a syndrome found in Japanese 
cultural 
contexts characterized by anxiety about 
and avoidance of interpersonal 
situations due to 
the thought, feeling, or conviction that 
the individual s appearance and actions in social 
interactions are inadequate or offensive to others. Taijin kyofusho 
includes two culture-related 
forms: 
a  sensitive type,  with extreme social 
sensitivity and anxiety about 
interpersonal 
interactions, and an  offensive type,  in which the major concern is offending others. Variants 
include major concerns about 
facial 
blushing (sekimen-kyofu), having an offensive body odor 
(jiko-shu-kyofu), inappropriate gaze (too much or too little eye contact, jiko-shisen-kyofu), and 
stiff or awkward facial 
expression or bodily movements (e.g., stiffening, trembling) or body 
deformity (shubo-kyofu). 


Taijin kyofusho 
is a broader construct 
than social 
anxiety disorder in DSM-5. Taijin kyofusho 
also includes syndromes with features of body dysmorphic disorder, olfactory reference 
syndrome, and delusional disorder; delusional disorder should be considered when concerns have 
a delusional quality, responding poorly to simple reassurance or counterexample. 


Related 
conditions 
in 
other cultural 
contexts. 
The distinctive symptoms of taijin kyofusho 
occur in 
specific cultural 
contexts and, to some extent, with more severe social 
anxiety cross-culturally. 
Similar syndromes are found in Korea (taein kong po) and other societies that 
place a strong 
emphasis on the self-conscious maintenance of appropriate social 
behavior in hierarchical 
interpersonal 
relationships. An interdependent 
self-construal, which emphasizes the relatedness 
of self to a collective and the identification of self in terms of social 
roles and relationships, may 
be a risk factor for taijin kyofusho 
symptoms across diverse cultures. The concern with offending 
others through inappropriate social 
behavior, characteristic of offensive-type taijin kyofusho, has 
also been described in several 
societies, including the United States, Australia, Indonesia, and 
New Zealand. 


Related 
conditions 
in 
DSM-5-TR. 
Social 
anxiety disorder, body dysmorphic disorder, delusional 
disorder, obsessive-compulsive disorder, olfactory reference syndrome (a type of other specified 
obsessive-compulsive and related disorder). Olfactory reference syndrome is related specifically 
to the jikoshu-kyofu variant of taijin kyofusho; this presentation is seen in various cultures outside 
Japan. 


880 



881 



Alternative DSM-5 Model 
for Personality 
Disorders 


Provided as an alternative 
to the extant 
personality disorders classification in 
Section II, this hybrid dimensional-categorical 
model 
in Section III defines personality disorder 
in terms of impairments in personality functioning and pathological 
personality traits. The 
inclusion of both models of personality disorder diagnosis in DSM-5 reflects the decision of the 
APA Board of Trustees to preserve continuity with current 
clinical 
practice, while also 
introducing an alternative approach that 
aims to address numerous shortcomings of the approach 
in Section II to personality disorders. For example, in the approach in Section II, symptoms 
meeting criteria for a specific personality disorder frequently also meet 
criteria for other 
personality disorders, and other specified or unspecified personality disorder is often the correct 
(but 
mostly uninformative) diagnosis, in the sense that 
individuals do not 
tend to present 
with 
patterns of symptoms that correspond with one and only one personality disorder. 


In the following alternative DSM-5 model, personality disorders are characterized by 
impairments in personality functioning 
and pathological 
personality traits. 
The specific 
personality disorder diagnoses that 
may be derived from 
this model 
include antisocial, avoidant, 
borderline, narcissistic, obsessive-compulsive, and schizotypal 
personality disorders. This 
approach also includes a diagnosis of personality disorder trait 
specified (PD-TS) that 
can be 
made when a personality disorder is considered present 
but 
the criteria for a specific disorder are 
not met. 


General Criteria for Personality Disorder 


General 
Criteria for Personality Disorder 


The 
essential features of 
a 
personality disorder are 


A. 
Moderate 
or greater impairment 
in 
personality (self/interpersonal) functioning. 
B. 
One 
or more 
pathological personality traits. 
C. 
The 
impairments in 
personality functioning 
and 
the 
individual s personality trait 
expression 
are 
relatively inflexible 
and 
pervasive 
across a 
broad 
range 
of 
personal and 
social situations. 
D. 
The 
impairments in 
personality functioning 
and 
the 
individual s personality trait 
expression 
are 
relatively stable 
across time, 
with 
onsets that 
can 
be 
traced 
back 
to 
at 
least 
adolescence 
or early adulthood. 
E. 
The 
impairments in 
personality functioning 
and 
the 
individual s personality trait 

expression 
are 
not 
better explained 
by another mental disorder. 


F. 
The 
impairments in 
personality functioning 
and 
the 
individual s personality trait 
expression 
are 
not 
solely attributable 
to 
the 
physiological effects of 
a 
substance 
or another medical condition 
(e.g., 
severe 
head 
trauma). 
G. 
The 
impairments in 
personality functioning 
and 
the 
individual s personality trait 
expression 
are 
not 
better understood 
as normal for an 
individual s developmental 
stage 
or sociocultural environment. 
882 


A diagnosis of a personality disorder requires two determinations: 
1) an assessment 
of the 
level 
of impairment 
in personality functioning, which is needed for Criterion A, and 2) an 
evaluation of pathological 
personality traits, which is required for Criterion B. The impairments 
in personality functioning and personality trait 
expression are relatively inflexible and pervasive 
across a broad range of personal 
and social 
situations (Criterion C); 
relatively stable across time, 
with onsets that 
can be traced back to at 
least 
adolescence or early adulthood (Criterion D); 
not 
better explained by another mental 
disorder (Criterion E); 
not 
attributable to the physiological 
effects of a substance or another medical 
condition (Criterion F); 
and not 
better understood as 
normal 
for an individual s developmental 
stage or sociocultural 
environment 
(Criterion G). All 
Section III personality disorders described by criteria sets, as well 
as PD-TS, meet 
these general 
criteria, by definition. 


Criterion A: Level 
of Personality Functioning 


Disturbances in self 
and interpersonal 
functioning constitute the core of personality 
psychopathology, and in this alternative diagnostic model 
they are evaluated on a continuum. 
Self functioning involves identity and self-direction; 
interpersonal 
functioning involves empathy 
and intimacy (see Table 1). The Level 
of Personality Functioning Scale (LPFS; 
see Table 2, pp. 
895 898) uses each of these elements to differentiate five levels of impairment, ranging from 
little or no impairment 
(i.e., healthy, adaptive functioning; 
Level 
0) to some (Level 
1), moderate 
(Level 2), severe (Level 3), and extreme (Level 4) impairment. 


Impairment 
in personality functioning predicts the presence of a personality disorder, and the 
severity of impairment 
predicts whether an individual 
has more than one personality disorder or 
one of the more typically severe personality disorders. A moderate level 
of impairment 
in 
personality functioning is required for the diagnosis of a personality disorder; 
this threshold is 
based on empirical 
evidence that 
the moderate level 
of impairment 
maximizes the ability of 
clinicians to accurately and efficiently identify personality disorder pathology. 


Criterion B: Pathological 
Personality Traits 


Pathological 
personality traits are organized into five broad domains: 
Negative Affectivity, 
Detachment, Antagonism, Disinhibition, and Psychoticism. Within the five broad trait domains 
are 25 specific trait facets 
that 
were developed initially from 
a review of existing trait 
models 
and subsequently through iterative research with samples of persons who sought 
mental 
health 
services. The full 
trait 
taxonomy is presented in Table 3 
(see pp. 899 901). The B 
criteria for the 



specific personality disorders comprise subsets of the 25 trait 
facets, based on meta-analytic 
reviews and empirical 
data on the relationships of the traits to DSM-IV personality disorder 
diagnoses. 


Criteria C and D: Pervasiveness and Stability 


Impairments in personality functioning and pathological 
personality traits are relatively 
pervasive across a range of personal 
and social 
contexts, as personality is defined as a pattern of 
perceiving, relating to, and thinking about 
the environment 
and oneself. The term 
relatively 
reflects the fact 
that 
all 
except 
the most 
extremely pathological 
personalities show some degree 
of adaptability. The pattern in personality disorders is maladaptive and relatively inflexible, 
which leads to disabilities in social, occupational, or other important 
pursuits, as individuals are 
unable to modify their thinking or behavior, even in the face of evidence that 
their approach is 
not 
working. The impairments in functioning and personality traits are also relatively 
stable. 
Personality traits the dispositions to behave or feel 
in certain ways are more stable than the 
symptomatic expressions of these dispositions, but 
personality traits can also change. 
Impairments in personality functioning are more stable than symptoms. 


883 


TABLE 
1 
Elements 
of personality 
functioning 


Self: 


1. Identity: Experience of oneself as unique, with clear boundaries between self and others; stability of self-esteem and accuracy 
of self-appraisal; capacity for, and ability to regulate, a range of emotional experience. 
2. Self-direction: Pursuit of coherent and meaningful short-term and life goals; utilization of constructive and prosocial internal 
standards of behavior; ability to self-reflect productively. 
Interpersonal: 


1. Empathy: Comprehension and appreciation of others  experiences and motivations; tolerance of differing perspectives; 
understanding of the effects of one s own behavior on others. 
2. Intimacy: Depth and duration of connection with others; desire and capacity for closeness; mutuality of regard reflected in 
interpersonal behavior. 
Criteria E, 
F, 
and G: Alternative Explanations for Personality Pathology 
(Differential 
Diagnosis) 


On some occasions, what 
appears to be a personality disorder may be better explained by another 
mental 
disorder, the physiological 
effects of a substance or another medical 
condition, or a 
normal 
developmental 
stage (e.g., adolescence, late life) or the individual s sociocultural 
environment. When another mental 
disorder is present, the diagnosis of a personality disorder is 
not 
made if the manifestations of the personality disorder clearly are an expression of the other 
mental 
disorder (e.g., if features of schizotypal 
personality disorder are present 
only in the 
context 
of schizophrenia). On the other hand, personality disorders can be accurately diagnosed 
in the presence of another mental 
disorder, such as major depressive disorder, and patients with 
other mental 
disorders should be assessed for comorbid personality disorders because personality 
disorders often impact 
the course of other mental 
disorders. Therefore, it 
is always appropriate to 
assess personality functioning and pathological 
personality traits to provide a context 
for other 



psychopathology. 


Specific Personality Disorders 


Section III includes diagnostic criteria for antisocial, avoidant, borderline, narcissistic, obsessive-
compulsive, and schizotypal 
personality disorders. Each personality disorder is defined by 
typical 
impairments in personality functioning (Criterion A) and characteristic pathological 
personality traits (Criterion B): 



Typical 
features of 
antisocial 
personality disorder 
are a failure to conform 
to lawful 
and ethical 
behavior, and an 
egocentric, callous lack of 
concern for 
others, accompanied by deceitfulness, irresponsibility, manipulativeness, and/or 
risk 
taking. 
Typical 
features of 
avoidant 
personality disorder 
are avoidance of 
social 
situations and inhibition in interpersonal 
relationships related to feelings of 
ineptitude and inadequacy, anxious preoccupation with negative evaluation and rejection, 
and fears of ridicule or embarrassment. 
Typicalfeatures of 
borderline personality disorder are instability of self-image, personal goals, interpersonal relationships, 
and affects, accompanied by impulsivity, risk taking, and/or hostility. 
Typical 
features of 
narcissistic personality disorder 
are variable and vulnerable self-esteem, with attempts at 
regulation 
through attention and approval seeking, and either overt or covert grandiosity. 
884 



Typical 
features of 
obsessive-compulsive personality disorder 
are difficulties in establishing and sustaining close 
relationships, associated with rigid perfectionism, inflexibility, and restricted emotional expression. 
Typical 
features of 
schizotypal personality disorder 
are impairments in the capacity for 
social 
and close relationships, and 
eccentricities in cognition, perception, and behavior 
that 
are associated with distorted self-image and incoherent 
personal 
goals and accompanied by suspiciousness and restricted emotional expression. 
The A and B 
criteria for the six specific personality disorders and for PD-TS 
follow. All 
personality disorders also meet 
criteria C 
through G of the General 
Criteria for Personality 
Disorder. 


Antisocial 
Personality Disorder 


Typical 
features of antisocial 
personality disorder are a failure to conform 
to lawful 
and ethical 
behavior, and an egocentric, callous lack of concern for others, accompanied by deceitfulness, 
irresponsibility, manipulativeness, and/or risk taking. Characteristic difficulties are apparent 
in 
identity, self-direction, empathy, and/or intimacy, as described below, along with specific 
maladaptive traits in the domains of Antagonism and Disinhibition. 


Proposed Diagnostic Criteria 


A. 
Moderate 
or greater impairment 
in 
personality functioning, 
manifested 
by 
characteristic difficulties in 
two 
or more 
of 
the 
following 
four areas: 

1. 
Identity: 
Egocentrism; 
self-esteem derived 
from personal gain, 
power, 
or 
pleasure. 
2. 
Self-direction: 
Goal setting 
based 
on 
personal gratification; 
absence 
of 
prosocial internal standards, 
associated 
with 
failure 
to 
conform to 
lawful or 
culturally normative 
ethical behavior. 
3. 
Empathy: 
Lack of 
concern 
for feelings, 
needs, 
or suffering 
of 
others; 
lack of 
remorse 
after hurting 
or mistreating 
another. 
4. 
Intimacy: 
Incapacity for mutually intimate 
relationships, 
as exploitation 
is a 
primary means of 
relating 
to 
others, 
including 
by deceit 
and 
coercion; 
use 
of 
dominance 
or intimidation 
to 
control others. 
B. 
Six or more 
of 
the 
following 
seven 
pathological personality traits: 
1. 
Manipulativeness 
(an 
aspect 
of 
Antagonism): 
Frequent 
use 
of 
subterfuge 
to 
influence 
or control others; 
use 
of 
seduction, 
charm, 
glibness, 
or 
ingratiation 
to 
achieve 
one s ends. 
2. 
Callousness 
(an 
aspect 
of 
Antagonism): 
Lack of 
concern 
for feelings or 
problems of 
others; 
lack of 
guilt 
or remorse 
about 
the 
negative 
or harmful 
effects of 
one s actions on 
others; 
aggression; 
sadism. 
3. 
Deceitfulness 
(an 
aspect 
of 
Antagonism): 
Dishonesty and 
fraudulence; 
misrepresentation 
of 
self; 
embellishment 
or fabrication 
when 
relating 
events. 
4. 
Hostility 
(an 
aspect 
of 
Antagonism): 
Persistent 
or frequent 
angry feelings; 
anger or irritability in 
response 
to 
minor slights and 
insults; 
mean, 
nasty, 
or 
vengeful behavior. 
5. 
Risk 
taking 
(an 
aspect 
of 
Disinhibition): 
Engagement 
in 
dangerous, 
risky, 
and 
potentially self-damaging 
activities, 
unnecessarily and 
without 
regard 
for 
consequences; 
boredom proneness and 
thoughtless initiation 
of 
activities to 
counter boredom; 
lack of 
concern 
for one s limitations and 
denial of 
the 
reality 
of 
personal danger. 
6. 
Impulsivity 
(an 
aspect 
of 
Disinhibition): 
Acting 
on 
the 
spur of 
the 
moment 
in 
response 
to 
immediate 
stimuli; 
acting 
on 
a 
momentary basis without 
a 
plan 
or 
consideration 
of 
outcomes; 
difficulty establishing 
and 
following 
plans. 
885 


7. 
Irresponsibility 
(an 
aspect 
of 
Disinhibition): 
Disregard 
for and 
failure 
to 
honor financial and 
other obligations or commitments; 
lack of 
respect 
for  
and 
lack of 
follow-through 
on agreements and 
promises. 
Note. 
The 
individual is at 
least 
18 
years of 
age. 
Specify 
if: 


With 
psychopathic 
features 


Specifiers. 
A distinct 
variant 
often termed psychopathy 
(or  primary  psychopathy) is marked by 
a lack of anxiety or fear and by a bold interpersonal 
style that 
may mask maladaptive behaviors 



(e.g., fraudulence). This psychopathic variant 
is characterized by low levels of anxiousness 
(Negative Affectivity domain) and withdrawal 
(Detachment 
domain) and high levels of attention 
seeking (Antagonism 
domain). High attention seeking and low withdrawal 
capture the social 
potency (assertive/dominant) component 
of psychopathy, whereas low anxiousness captures the 
stress immunity (emotional stability/resilience) component. 


In addition to psychopathic features, trait 
and personality functioning specifiers may be used 
to record other personality features that 
may be present 
in antisocial 
personality disorder but 
are 
not 
required for the diagnosis. For example, traits of Negative Affectivity (e.g., anxiousness) are 
not 
diagnostic criteria for antisocial 
personality disorder (see Criterion B) but 
can be specified 
when appropriate. Furthermore, although moderate or greater impairment 
in personality 
functioning is required for the diagnosis of antisocial 
personality disorder (Criterion A), the level 
of personality functioning can also be specified. 


Avoidant Personality Disorder 


Typical 
features of avoidant 
personality disorder are avoidance of social 
situations and inhibition 
in interpersonal 
relationships related to feelings of ineptitude and inadequacy, anxious 
preoccupation with negative evaluation and rejection, and fears of ridicule or embarrassment. 
Characteristic difficulties are apparent 
in identity, self-direction, empathy, and/or intimacy, as 
described below, along with specific maladaptive traits in the domains of Negative Affectivity 
and Detachment. 


Proposed Diagnostic Criteria 


A. 
Moderate 
or greater impairment 
in 
personality functioning, 
manifested 
by 
characteristic difficulties in 
two 
or more 
of 
the 
following 
four areas: 
1. 
Identity: 
Low self-esteem associated 
with 
self-appraisal as socially inept, 
personally unappealing, 
or inferior; 
excessive 
feelings of 
shame. 
2. 
Self-direction: 
Unrealistic standards for behavior associated 
with 
reluctance 
to 
pursue 
goals, 
take 
personal risks, 
or engage 
in 
new activities involving 
interpersonal contact. 
3. 
Empathy: 
Preoccupation 
with, 
and 
sensitivity to, 
criticism or rejection, 
associated 
with 
distorted 
inference 
of 
others  perspectives as negative. 
4. 
Intimacy: 
Reluctance 
to 
get 
involved 
with 
people 
unless being 
certain 
of 
being 
liked; 
diminished 
mutuality within 
intimate 
relationships because 
of 
fear 
of 
being 
shamed 
or ridiculed. 
B. 
Three 
or more 
of 
the 
following 
four pathological personality traits, 
one 
of 
which 
must 
be 
(1) Anxiousness: 
1. 
Anxiousness 
(an 
aspect 
of 
Negative 
Affectivity): 
Intense 
feelings of 
nervousness, 
tenseness, 
or panic, 
often 
in 
reaction 
to 
social situations; 
worry 
about 
the 
negative 
effects of 
past 
unpleasant 
experiences and 
future 
negative 
possibilities; 
feeling 
fearful, 
apprehensive, 
or threatened 
by uncertainty; 
fears 
of 
embarrassment. 

2. 
Withdrawal 
(an 
aspect 
of 
Detachment): 
Reticence 
in 
social situations; 
avoidance 
of 
social contacts and 
activity; 
lack of 
initiation 
of 
social contact. 
886 


3. 
Anhedonia 
(an 
aspect 
of 
Detachment): 
Lack of 
enjoyment 
from, 
engagement 
in, 
or energy for life s experiences; 
deficits in 
the 
capacity to 
feel 
pleasure 
or take 
interest 
in 
things. 
4. 
Intimacy 
avoidance 
(an 
aspect 
of 
Detachment): 
Avoidance 
of 
close 
or 
romantic relationships, 
interpersonal attachments, 
and 
intimate 
sexual 
relationships. 
Specifiers. 
Considerable heterogeneity in the form 
of additional 
personality traits is found among 
individuals diagnosed with avoidant 
personality disorder. Trait 
and level 
of personality 
functioning specifiers can be used to record additional 
personality features that 
may be present 
in 
avoidant 
personality disorder. For example, other Negative Affectivity traits (e.g., depressivity, 
separation insecurity, submissiveness, suspiciousness, hostility) are not 
diagnostic criteria for 
avoidant 
personality disorder (see Criterion B) but 
can be specified when appropriate. 
Furthermore, although moderate or greater impairment 
in personality functioning is required for 
the diagnosis of avoidant 
personality disorder (Criterion A), the level 
of personality functioning 
also can be specified. 


Borderline Personality Disorder 


Typical 
features of borderline personality disorder are instability of self-image, personal 
goals, 
interpersonal 
relationships, and affects, accompanied by impulsivity, risk taking, and/or hostility. 
Characteristic difficulties are apparent 
in identity, self-direction, empathy, and/or intimacy, as 
described below, along with specific maladaptive traits in the domain of Negative Affectivity, 
and also Antagonism and/or Disinhibition. 


Proposed Diagnostic Criteria 


A. 
Moderate 
or greater impairment 
in 
personality functioning, 
manifested 
by 
characteristic difficulties in 
two 
or more 
of 
the 
following 
four areas: 
1. 
Identity: 
Markedly impoverished, 
poorly developed, 
or unstable 
self-image, 
often 
associated 
with 
excessive 
self-criticism; 
chronic feelings of 
emptiness; 
dissociative 
states under stress. 
2. 
Self-direction: 
Instability in 
goals, 
aspirations, 
values, 
or career plans. 
3. 
Empathy: 
Compromised 
ability to 
recognize 
the 
feelings and 
needs of 
others 
associated 
with 
interpersonal hypersensitivity (i.e., 
prone 
to 
feel slighted 
or 
insulted); 
perceptions of 
others selectively biased 
toward 
negative 
attributes 
or vulnerabilities. 
4. 
Intimacy: 
Intense, 
unstable, 
and 
conflicted 
close 
relationships, 
marked 
by 

mistrust, 
neediness, 
and 
anxious preoccupation 
with 
real or imagined 
abandonment; 
close 
relationships often 
viewed 
in 
extremes of 
idealization 
and 
devaluation 
and 
alternating 
between 
overinvolvement 
and 
withdrawal. 


B. 
Four or more 
of 
the 
following 
seven 
pathological personality traits, 
at 
least 
one 
of 
which 
must 
be 
(5) Impulsivity, 
(6) Risk taking, 
or (7) Hostility: 
1. 
Emotional 
lability 
(an 
aspect 
of 
Negative 
Affectivity): 
Unstable 
emotional 
experiences and 
frequent 
mood 
changes; 
emotions that 
are 
easily aroused, 
intense, 
and/or out 
of 
proportion 
to 
events and 
circumstances. 
2. 
Anxiousness 
(an 
aspect 
of 
Negative 
Affectivity): 
Intense 
feelings of 
nervousness, 
tenseness, 
or panic, 
often 
in 
reaction 
to 
interpersonal stresses; 
worry about 
the 
negative 
effects of 
past 
unpleasant 
experiences and 
future 
negative 
possibilities; 
feeling 
fearful, 
apprehensive, 
or threatened 
by 
uncertainty; 
fears of 
falling 
apart 
or losing 
control. 
3. 
Separation 
insecurity 
(an 
aspect 
of 
Negative 
Affectivity): 
Fears of 
rejection 
by and/or separation 
from significant 
others, 
associated 
with 
fears of 
excessive 
dependency and 
complete 
loss of 
autonomy. 
887 


4. 
Depressivity 
(an 
aspect 
of 
Negative 
Affectivity): 
Frequent 
feelings of 
being 
down, 
miserable, 
and/or hopeless; 
difficulty recovering 
from such 
moods; 
pessimism about 
the 
future; 
pervasive 
shame; 
feelings of 
inferior self-worth; 
thoughts of 
suicide 
and 
suicidal behavior. 
5. 
Impulsivity 
(an 
aspect 
of 
Disinhibition): 
Acting 
on 
the 
spur of 
the 
moment 
in 
response 
to 
immediate 
stimuli; 
acting 
on 
a 
momentary basis without 
a 
plan 
or 
consideration 
of 
outcomes; 
difficulty establishing 
or following 
plans; 
a 
sense 
of 
urgency and 
self-harming 
behavior under emotional distress. 
6. 
Risk 
taking 
(an 
aspect 
of 
Disinhibition): 
Engagement 
in 
dangerous, 
risky, 
and 
potentially self-damaging 
activities, 
unnecessarily and 
without 
regard 
to 
consequences; 
lack of 
concern 
for one s limitations and 
denial of 
the 
reality of 
personal danger. 
7. 
Hostility 
(an 
aspect 
of 
Antagonism): 
Persistent 
or frequent 
angry feelings; 
anger or irritability in 
response 
to 
minor slights and 
insults. 
Specifiers. 
Trait 
and level 
of personality functioning specifiers may be used to record additional 
personality features that 
may be present 
in borderline personality disorder but 
are not 
required 
for the diagnosis. For example, traits of Psychoticism 
(e.g., cognitive and perceptual 
dysregulation) are not 
diagnostic criteria for borderline personality disorder (see Criterion B) but 
can be specified when appropriate. Furthermore, although moderate or greater impairment 
in 
personality functioning is required for the diagnosis of borderline personality disorder (Criterion 
A), the level of personality functioning can also be specified. 


Narcissistic Personality Disorder 



Typical 
features of narcissistic personality disorder are variable and vulnerable self-esteem, with 
attempts at 
regulation through attention and approval 
seeking, and either overt 
or covert 
grandiosity. Characteristic difficulties are apparent 
in identity, self-direction, empathy, and/or 
intimacy, as described below, along with specific maladaptive traits in the domain of 
Antagonism. 


Proposed Diagnostic Criteria 


A. 
Moderate 
or greater impairment 
in 
personality functioning, 
manifested 
by 
characteristic difficulties in 
two 
or more 
of 
the 
following 
four areas: 
1. 
Identity: 
Excessive 
reference 
to 
others for self-definition 
and 
self-esteem 
regulation; 
exaggerated 
self-appraisal inflated 
or deflated, 
or vacillating 
between 
extremes; 
emotional regulation 
mirrors fluctuations in 
self-esteem. 
2. 
Self-direction: 
Goal setting 
based 
on 
gaining 
approval from others; 
personal 
standards unreasonably high 
in 
order to 
see 
oneself 
as exceptional, 
or too 
low based 
on 
a 
sense 
of 
entitlement; 
often 
unaware 
of 
own 
motivations. 
3. 
Empathy: 
Impaired 
ability to 
recognize 
or identify with 
the 
feelings and 
needs 
of 
others; 
excessively attuned 
to 
reactions of 
others, 
but 
only if 
perceived 
as 
relevant 
to 
self; 
over- or underestimation 
of 
own 
effect 
on 
others. 
4. 
Intimacy: 
Relationships largely superficial and 
exist 
to 
serve 
self-esteem 
regulation; 
mutuality constrained 
by little 
genuine 
interest 
in 
others  
experiences and 
predominance 
of 
a 
need 
for personal gain. 
B. 
Both 
of 
the 
following 
pathological personality traits: 
1. 
Grandiosity 
(an 
aspect 
of 
Antagonism): 
Feelings of 
entitlement, 
either overt 
or covert; 
self-centeredness; 
firmly holding 
to 
the 
belief 
that 
one 
is better than 
others; 
condescension 
toward 
others. 
888 


2. 
Attention 
seeking 
(an 
aspect 
of 
Antagonism): 
Excessive 
attempts to 
attract 
and 
be 
the 
focus of 
the 
attention 
of 
others; 
admiration 
seeking. 
Specifiers. 
Trait 
and personality functioning specifiers may be used to record additional 
personality features that 
may be present 
in narcissistic personality disorder but 
are not 
required 
for the diagnosis. For example, other traits of Antagonism 
(e.g., manipulativeness, deceitfulness, 
callousness) are not 
diagnostic criteria for narcissistic personality disorder (see Criterion B) but 
can be specified when more pervasive antagonistic features (e.g.,  malignant 
narcissism ) are 
present. Other traits of Negative Affectivity (e.g., depressivity, anxiousness) can be specified to 
record more  vulnerable  presentations. Furthermore, although moderate or greater impairment 
in personality functioning is required for the diagnosis of narcissistic personality disorder 
(Criterion A), the level of personality functioning can also be specified. 



Obsessive-Compulsive Personality Disorder 


Typical 
features of obsessive-compulsive personality disorder are difficulties in establishing and 
sustaining close relationships, associated with rigid perfectionism, inflexibility, and restricted 
emotional 
expression. Characteristic difficulties are apparent 
in identity, self-direction, empathy, 
and/or intimacy, as described below, along with specific maladaptive traits in the domains of 
Negative Affectivity and/or Detachment. 


Proposed Diagnostic Criteria 


A. 
Moderate 
or greater impairment 
in 
personality functioning, 
manifested 
by 
characteristic difficulties in 
two 
or more 
of 
the 
following 
four areas: 
1. 
Identity: 
Sense 
of 
self 
derived 
predominantly from work or productivity; 
constricted 
experience 
and 
expression 
of 
strong 
emotions. 
2. 
Self-direction: 
Difficulty completing 
tasks and 
realizing 
goals, 
associated 
with 
rigid 
and 
unreasonably high 
and 
inflexible 
internal standards of 
behavior; 
overly conscientious and 
moralistic attitudes. 
3. 
Empathy: 
Difficulty understanding 
and 
appreciating 
the 
ideas, 
feelings, 
or 
behaviors of 
others. 
4. 
Intimacy: 
Relationships seen 
as secondary to 
work and 
productivity; 
rigidity 
and 
stubbornness negatively affect 
relationships with 
others. 
B. 
Three 
or more 
of 
the 
following 
four pathological personality traits, 
one 
of 
which 
must 
be 
(1) Rigid 
perfectionism: 
1. 
Rigid 
perfectionism 
(an 
aspect 
of 
extreme 
Conscientiousness [the 
opposite 
pole 
of 
Disinhibition]): 
Rigid 
insistence 
on 
everything 
being 
flawless, 
perfect, 
and 
without 
errors or faults, 
including 
one s own 
and 
others  performance; 
sacrificing 
of 
timeliness to 
ensure 
correctness in 
every detail; 
believing 
that 
there 
is only one 
right 
way to 
do 
things; 
difficulty changing 
ideas and/or 
viewpoint; 
preoccupation 
with 
details, 
organization, 
and 
order. 
2. 
Perseveration 
(an 
aspect 
of 
Negative 
Affectivity): 
Persistence 
at 
tasks long 
after the 
behavior has ceased 
to 
be 
functional or effective; 
continuance 
of 
the 
same 
behavior despite 
repeated 
failures. 
3. 
Intimacy 
avoidance 
(an 
aspect 
of 
Detachment): 
Avoidance 
of 
close 
or 
romantic relationships, 
interpersonal attachments, 
and 
intimate 
sexual 
relationships. 
4. 
Restricted 
affectivity 
(an 
aspect 
of 
Detachment): 
Little 
reaction 
to 
emotionally arousing 
situations; 
constricted 
emotional experience 
and 
expression; 
indifference 
or coldness. 
889 
Specifiers. 
Trait 
and personality functioning specifiers may be used to record additional 



personality features that 
may be present 
in obsessive-compulsive personality disorder but 
are not 
required for the diagnosis. For example, other traits of Negative Affectivity (e.g., anxiousness) 
are not diagnostic criteria for obsessive-compulsive personality disorder (see Criterion B) but can 
be specified when appropriate. Furthermore, although moderate or greater impairment 
in 
personality functioning is required for the diagnosis of obsessive-compulsive personality 
disorder (Criterion A), the level of personality functioning can also be specified. 


Schizotypal 
Personality Disorder 


Typical 
features of schizotypal 
personality disorder are impairments in the capacity for social 
and close relationships and eccentricities in cognition, perception, and behavior that 
are 
associated with distorted self-image and incoherent 
personal 
goals and accompanied by 
suspiciousness and restricted emotional 
expression. Characteristic difficulties are apparent 
in 
identity, self-direction, empathy, and/or intimacy, along with specific maladaptive traits in the 
domains of Psychoticism and Detachment. 


Proposed Diagnostic Criteria 


A. 
Moderate 
or greater impairment 
in 
personality functioning, 
manifested 
by 
characteristic difficulties in 
two 
or more 
of 
the 
following 
four areas: 
1. 
Identity: 
Confused 
boundaries between 
self 
and 
others; 
distorted 
self-
concept; 
emotional expression 
often 
not 
congruent 
with 
context 
or internal 
experience. 
2. 
Self-direction: 
Unrealistic or incoherent 
goals; 
no 
clear set 
of 
internal 
standards. 
3. 
Empathy: 
Pronounced 
difficulty understanding 
impact 
of 
own 
behaviors on 
others; 
frequent 
misinterpretations of 
others  motivations and 
behaviors. 
4. 
Intimacy: 
Marked 
impairments in 
developing 
close 
relationships, 
associated 
with 
mistrust 
and 
anxiety. 
B. 
Four or more 
of 
the 
following 
six pathological personality traits: 
1. 
Cognitive 
and 
perceptual 
dysregulation 
(an 
aspect 
of 
Psychoticism): 
Odd 
or unusual thought 
processes; 
vague, 
circumstantial, 
metaphorical, 
overelaborate, 
or stereotyped 
thought 
or speech; 
odd 
sensations in 
various 
sensory modalities. 
2. 
Unusual 
beliefs 
and 
experiences 
(an 
aspect 
of 
Psychoticism): 
Thought 
content 
and 
views of 
reality that 
are 
viewed 
by others as bizarre 
or 
idiosyncratic; 
unusual experiences of 
reality. 
3. 
Eccentricity 
(an 
aspect 
of 
Psychoticism): 
Odd, 
unusual, 
or bizarre 
behavior 
or appearance; 
saying 
unusual or inappropriate 
things. 
4. 
Restricted 
affectivity 
(an 
aspect 
of 
Detachment): 
Little 
reaction 
to 
emotionally arousing 
situations; 
constricted 
emotional experience 
and 
expression; 
indifference 
or coldness. 

5. 
Withdrawal 
(an 
aspect 
of 
Detachment): 
Preference 
for being 
alone 
to 
being 
with 
others; 
reticence 
in 
social situations; 
avoidance 
of 
social contacts and 
activity; 
lack of 
initiation 
of 
social contact. 
6. 
Suspiciousness 
(an 
aspect 
of 
Detachment): 
Expectations of and 
heightened 
sensitivity to signs of 
interpersonal ill-intent 
or harm; 
doubts 
about 
loyalty and 
fidelity of 
others; 
feelings of 
persecution. 
Specifiers. 
Trait 
and personality functioning specifiers may be used to record additional 
personality features that 
may be present 
in schizotypal 
personality disorder but 
are not 
required 
for the diagnosis. For example, traits of Negative Affectivity (e.g., depressivity, anxiousness) are 
not diagnostic criteria for schizotypal personality disorder (see Criterion B) 


890 


but 
can be specified when appropriate. Furthermore, although moderate or greater impairment 
in 
personality functioning is required for the diagnosis of schizotypal 
personality disorder 
(Criterion A), the level of personality functioning can also be specified. 


Personality Disorder Trait Specified 


Proposed Diagnostic Criteria 


A. 
Moderate 
or greater impairment 
in 
personality functioning, 
manifested 
by 
difficulties in 
two 
or more 
of 
the 
following 
four areas: 
1. 
Identity 
2. 
Self-direction 
3. 
Empathy 
4. 
Intimacy 
B. 
One 
or more 
pathological personality trait 
domains OR specific trait 
facets within 
domains, 
considering 
ALL 
of 
the 
following 
domains: 
1. 
Negative 
Affectivity 
(vs. 
Emotional Stability): 
Frequent 
and 
intense 
experiences of 
high 
levels of 
a 
wide 
range 
of 
negative 
emotions (e.g., 
anxiety, 
depression, 
guilt/shame, 
worry, 
anger), 
and 
their behavioral (e.g., 
self-harm) 
and 
interpersonal (e.g., 
dependency) manifestations. 
2. 
Detachment 
(vs. 
Extraversion): 
Avoidance 
of 
socioemotional experience, 
including 
both 
withdrawal from interpersonal interactions, 
ranging 
from 
casual, 
daily interactions to 
friendships to 
intimate 
relationships, 
as well as 
restricted 
affective 
experience 
and 
expression, 
particularly limited 
hedonic 
capacity. 
3. 
Antagonism 
(vs. 
Agreeableness): 
Behaviors that 
put 
the 
individual at 
odds 
with 
other people, 
including 
an 
exaggerated 
sense 
of 
self-importance 
and 
a 

concomitant 
expectation 
of 
special treatment, 
as well as a 
callous antipathy 
toward 
others, 
encompassing 
both 
unawareness of 
others  needs and 
feelings and 
a 
readiness to 
use 
others in 
the 
service 
of 
self-enhancement. 


4. 
Disinhibition 
(vs. 
Conscientiousness): 
Orientation 
toward 
immediate 
gratification, 
leading 
to 
impulsive 
behavior driven 
by current 
thoughts, 
feelings, 
and 
external stimuli, 
without 
regard 
for past 
learning 
or consideration 
of 
future 
consequences. 
5. 
Psychoticism 
(vs. 
Lucidity): 
Exhibiting 
a 
wide 
range 
of 
culturally incongruent 
odd, 
eccentric, 
or unusual behaviors and 
cognitions, 
including 
both 
process 
(e.g., 
perception, 
dissociation) and 
content 
(e.g., 
beliefs). 
Subtypes. 
Because personality features vary continuously along multiple trait 
dimensions, a 
comprehensive set 
of potential 
expressions of PD-TS 
can be represented by DSM-5 s 
dimensional 
model 
of maladaptive personality trait 
variants (see Table 3, pp. 899 901). Thus, 
subtypes are unnecessary for PD-TS, and instead, the descriptive elements that 
constitute 
personality are provided, arranged in an empirically based model. This arrangement 
allows 
clinicians to tailor the description of each individual s personality disorder profile, considering 
all 
five broad domains of personality trait 
variation and drawing on the descriptive features of 
these domains as needed to characterize the individual. 


Specifiers. 
The specific personality features of individuals are always recorded in evaluating 
Criterion B, so the combination of personality features characterizing an individual 
directly 
constitutes the specifiers in each case. For example, two individuals who are both characterized 
by emotional 
lability, hostility, and depressivity may differ such that 
the first 
individual 
is 
characterized additionally by callousness, whereas the second is not. 


891 


Personality Disorder Scoring Algorithms 


The requirement 
for any two of the four A criteria for each of the six personality disorders was 
based on maximizing the relationship of these criteria to their corresponding personality 
disorder. Diagnostic thresholds for the B 
criteria were also set 
empirically to minimize change in 
prevalence of the disorders from 
DSM-IV and overlap with other personality disorders, and to 
maximize relationships with functional 
impairment. The resulting diagnostic criteria sets 
represent 
clinically useful 
personality disorders with high fidelity, in terms of core impairments 
in personality functioning of varying degrees of severity and constellations of pathological 
personality traits. 


Personality Disorder Diagnosis 


Individuals who have a pattern of impairment 
in personality functioning and maladaptive traits 
that 
matches one of the six defined personality disorders should be diagnosed with that 
personality disorder. If an individual 
also has one or even several 
prominent 
traits that 
may have 
clinical 
relevance in addition to those required for the diagnosis (e.g., see narcissistic personality 



disorder), the option exists for these to be noted as specifiers. Individuals whose personality 
functioning or trait 
pattern is substantially different 
from 
that 
of any of the six specific 
personality disorders should be diagnosed with PD-TS. The individual 
may not 
meet 
the required 
number of A or B 
criteria and, thus, have a subthreshold presentation of a personality disorder. 
The individual 
may have a mix of features of personality disorder types or some features that 
are 
less characteristic of a type and more accurately considered a mixed or atypical 
presentation. The 
specific level 
of impairment 
in personality functioning and the pathological 
personality traits that 
characterize the individual s personality can be specified for PD-TS, using the Level 
of 
Personality Functioning Scale (Table 2) and the pathological 
trait 
taxonomy (Table 3). The 
current 
diagnoses of paranoid, schizoid, histrionic, and dependent 
personality disorders are 
represented also by the diagnosis of PD-TS; 
these are defined by moderate or greater impairment 
in personality functioning and can be specified by the relevant 
pathological 
personality trait 
combinations. 


Level of 
Personality Functioning 


Like most 
human tendencies, personality functioning is distributed on a continuum. Central 
to 
functioning and adaptation are individuals  characteristic ways of thinking about 
and 
understanding themselves and their interactions with others. An optimally functioning individual 
has a complex, fully elaborated, and well-integrated psychological 
world that 
includes a mostly 
positive, volitional, and adaptive self-concept; 
a rich, broad, and appropriately regulated 
emotional 
life; 
and the capacity to behave as a productive member of society with reciprocal 
and 
fulfilling interpersonal 
relationships. At 
the opposite end of the continuum, an individual 
with 
severe personality pathology has an impoverished, disorganized, and/or conflicted psychological 
world that 
includes a weak, unclear, and maladaptive self-concept; 
a propensity to negative, 
dysregulated emotions; 
and a deficient 
capacity for adaptive interpersonal 
functioning and social 
behavior. 


Self 
and Interpersonal 
Functioning Dimensional 
Definition 


Generalized severity may be the most 
important 
single predictor of concurrent 
and prospective 
dysfunction in assessing personality psychopathology. Personality disorders are optimally 
characterized by a generalized personality severity continuum with additional 


892 


specification of stylistic elements, derived from 
personality disorder symptom 
constellations and 
personality traits. At 
the same time, the core of personality psychopathology is impairment 
in 
ideas and feelings regarding self and interpersonal 
relationships; 
this notion is consistent 
with 
multiple theories of personality disorder and their research bases. The components of the Level 
of Personality Functioning Scale identity, self-direction, empathy, and intimacy (see Table 1) 
 are particularly central in describing a personality functioning continuum. 


Mental 
representations of the self and interpersonal 
relationships are reciprocally influential 
and inextricably tied, affect 
the nature of interaction with mental 
health professionals, and can 
have a significant 
impact 
on both treatment 
efficacy and outcome, underscoring the importance 
of assessing an individual s characteristic self-concept 
as well 
as views of other people and 



relationships. Although the degree of disturbance in the self and interpersonal 
functioning is 
continuously distributed, it 
is useful 
to consider the level 
of impairment 
in functioning for 
clinical characterization and for treatment planning and prognosis. 


Rating Level 
of Personality Functioning 


To use the Level 
of Personality Functioning Scale (LPFS), the clinician selects the level 
that 
most 
closely captures the individual s current 
overall 
level 
of impairment 
in personality 
functioning. The rating is necessary for the diagnosis of a personality disorder (moderate or 
greater impairment) and can be used to specify the severity of impairment 
present 
for an 
individual 
with any personality disorder at 
a given point 
in time. The LPFS 
may also be used as a 
global 
indicator of personality functioning without 
specification of a personality disorder 
diagnosis, or in the event that personality impairment is subthreshold for a disorder diagnosis. 


Personality Traits 


Definition and Description 


Criterion B 
in the alternative model 
involves assessments of personality traits that 
are grouped 
into five domains. A personality trait 
is a tendency to feel, perceive, behave, and think in 
relatively consistent 
ways across time and across situations in which the trait 
may manifest. For 
example, individuals with a high level 
of the personality trait 
of anxiousness 
would tend to feel 
anxious readily, including in circumstances in which most 
people would be calm 
and relaxed. 
Individuals high in trait anxiousness also would perceive situations to be anxiety-provoking more 
frequently than would individuals with lower levels of this trait, and those high in the trait 
would 
tend to behave 
so as to avoid situations that 
they think 
would make them 
anxious. They would 
thereby tend to think about the world as more anxiety provoking than other people. 


Importantly, individuals high in trait 
anxiousness would not 
necessarily be anxious at 
all 
times and in all 
situations. Individuals  trait 
levels also can and do change throughout 
life. Some 
changes are very general 
and reflect 
maturation (e.g., teenagers generally are higher on trait 
impulsivity than are older adults), whereas other changes reflect individuals  life experiences. 


Dimensionality 
of 
personality 
traits. 
All 
individuals can be located on the spectrum 
of trait 
dimensions; 
that 
is, personality traits apply to everyone in different 
degrees rather than being 
present 
versus absent. Moreover, personality traits, including those identified specifically in the 
Section III model, exist 
on a spectrum 
with two opposing poles. For example, the opposite of the 
trait 
of callousness 
is the tendency to be empathic and kind-hearted, even in circumstances in 
which most persons would not feel that way. Hence, 


893 


although in Section III this trait 
is labeled callousness, 
because that 
pole of the dimension is the 
primary focus, it 
could be described in full 
as callousness versus kind-heartedness. 
Moreover, its 
opposite pole can be recognized and may not 
be adaptive in all 
circumstances (e.g., individuals 
who, due to extreme kind-heartedness, repeatedly allow themselves to be taken advantage of by 
unscrupulous others). 



Hierarchical 
structure 
of 
personality. 
Some trait 
terms are quite specific (e.g.,  talkative ) and 
describe a narrow range of behaviors, whereas others are quite broad (e.g., Detachment) and 
characterize a wide range of behavioral 
propensities. Broad trait 
dimensions are called domains, 
and specific trait 
dimensions are called facets. 
Personality trait 
domains 
comprise a spectrum 
of 
more specific personality facets 
that 
tend to occur together. For example, withdrawal 
and 
anhedonia are specific trait 
facets 
in the trait 
domain 
of Detachment. Despite some cross-cultural 
variation in personality trait 
facets, the broad domains they collectively comprise are relatively 
consistent across cultures. 


The Personality Trait Model 


The Section III personality trait 
system 
includes five broad domains of personality trait 
variation 
 Negative Affectivity (vs. Emotional 
Stability), Detachment 
(vs. Extraversion), Antagonism 
(vs. Agreeableness), Disinhibition (vs. Conscientiousness), and Psychoticism 
(vs. Lucidity)  
comprising 25 specific personality trait 
facets. Table 3 
provides definitions of all 
personality 
domains and facets. These five broad domains are maladaptive variants of the five domains of 
the extensively validated and replicated personality model 
known as the  Big Five,  or Five 
Factor Model 
of personality (FFM), and are also similar to the domains of the Personality 
Psychopathology Five (PSY-5). The specific 25 facets represent 
a list 
of personality facets 
chosen for their clinical relevance. 


Although the Trait 
Model 
focuses on personality traits associated with psychopathology, 
there are healthy, adaptive, and resilient 
personality traits identified as the polar opposites of 
these traits, as noted in the parentheses above (i.e., Emotional 
Stability, Extraversion, 
Agreeableness, Conscientiousness, and Lucidity). Their presence can greatly mitigate the effects 
of mental 
disorders and facilitate coping and recovery from 
traumatic injuries and other medical 
illness. 


Distinguishing Traits, 
Symptoms, 
and Specific Behaviors 


Although traits are by no means immutable and do change throughout 
the life span, they show 
relative consistency compared with symptoms and specific behaviors. For example, a person 
may behave impulsively at 
a specific time for a specific reason (e.g., a person who is rarely 
impulsive suddenly decides to spend a great 
deal 
of money on a particular item 
because of an 
unusual 
opportunity to purchase something of unique value), but 
it 
is only when behaviors 
aggregate across time and circumstance, such that 
a pattern of behavior distinguishes between 
individuals, that 
they reflect 
traits. Nevertheless, it 
is important 
to recognize, for example, that 
even people who are impulsive are not 
acting impulsively all 
of the time. A trait 
is a tendency or 
disposition toward specific behaviors; 
a specific behavior is an instance or manifestation of a 
trait. 


Similarly, traits are distinguished from 
most 
symptoms because symptoms tend to wax and 
wane, whereas traits are relatively more stable. For example, individuals with higher levels of 
depressivity 
have a greater likelihood of experiencing discrete episodes of a depressive disorder 
and of showing the symptoms of these disorders, such as difficulty concentrating. However, even 
patients who have a trait 
propensity to depressivity 
typically cycle through distinguishable 
episodes of mood disturbance, and specific symptoms such as difficulty concentrating tend to 
wax and wane in concert with specific episodes, so they do 



894 


not 
form 
part 
of the trait 
definition. Importantly, however, symptoms and traits are both 
amenable to intervention, and many interventions targeted at 
symptoms can affect 
the longer 
term patterns of personality functioning that are captured by personality traits. 


Assessment of the DSM-5 Section III 
Personality Trait Model 


The clinical 
utility of the Section 
III multidimensional 
personality trait 
model 
lies in its ability to 
focus attention on multiple relevant 
areas of personality variation in each individual 
patient. 
Rather than focusing attention on the identification of one and only one optimal 
diagnostic label, 
clinical 
application of the Section III personality trait 
model 
involves reviewing all 
five broad 
personality domains portrayed in Table 3. The clinical 
approach to personality is similar to the 
well-known review of systems in clinical 
medicine. For example, an individual s presenting 
complaint 
may focus on a specific neurological 
symptom, yet 
during an initial 
evaluation 
clinicians still 
systematically review functioning in all 
relevant 
systems (e.g., cardiovascular, 
respiratory, gastrointestinal), lest 
an important 
area of diminished functioning and corresponding 
opportunity for effective intervention be missed. 


Clinical 
use of the Section III personality trait 
model 
proceeds similarly. An initial 
inquiry 
reviews all 
five broad domains of personality. This systematic review is facilitated by the use of 
formal 
psychometric instruments designed to measure specific facets and domains of personality. 
For example, the personality trait 
model 
is operationalized in the Personality Inventory for DSM5 
(PID-5), which can be completed in its self-report 
form 
by patients and in its informant-report 
form 
by those who know the patient 
well 
(e.g., a spouse). A detailed clinical 
assessment 
would 
involve collection of both patient- and informant-report 
data on all 
25 facets of the personality 
trait 
model. However, if this is not 
possible, due to time or other constraints, assessment 
focused 
at 
the five-domain level 
is an acceptable clinical 
option when only a general 
(vs. detailed) 
portrait 
of a patient s personality is needed (see Criterion B 
of PD-TS). However, if personality-
based problems are the focus of treatment, then it 
will 
be important 
to assess individuals  trait 
facets as well as domains. 


Because personality traits are continuously distributed in the population, an approach to 
making the judgment 
that 
a specific trait 
is elevated (and therefore is present 
for diagnostic 
purposes) could involve comparing individuals  personality trait 
levels with population norms 
and/or clinical 
judgment. If a trait 
is elevated that 
is, formal 
psychometric testing and/or 
interview data support 
the clinical 
judgment 
of elevation then it 
is considered as contributing to 
meeting Criterion B of Section III personality disorders. 


Clinical 
Utility of the Multidimensional 
Personality Functioning and 
Trait Model 


Disorder and trait 
constructs each add value to the other in predicting important 
antecedent 
(e.g., 
family history, history of child abuse), concurrent 
(e.g., functional 
impairment, medication use), 
and predictive (e.g., hospitalization, suicide attempts) variables. DSM-5 impairments in 
personality functioning and pathological 
personality traits each contribute independently to 
clinical 
decisions about 
degree of disability; 
risks for self-harm, violence, and criminality; 
recommended treatment 
type and intensity; 
and prognosis all 
important 
aspects of the utility of 



psychiatric diagnoses. Notably, knowing the level 
of an individual s personality functioning and 
his or her pathological 
trait 
profile also provides the clinician with a rich base of information and 
is valuable in treatment 
planning and in predicting the course and outcome of many mental 
disorders in addition to personality disorders. Therefore, assessment 
of personality functioning 
and pathological 
personality traits may be relevant 
whether an individual 
has a personality 
disorder or not. 


895 


TABLE 
2 
Level 
of Personality 
Functioning 
Scale 
SELF 
INTERPERSONAL 
Level 
of 
impairment 
Identity 
Self-direction 
Empathy 
Intimacy 


0 Little or 
no 
impairment 


1 Some 
impairment 


896 


Has ongoing awareness 
of a unique self; 
maintains role-
appropriate 
boundaries. 


Has consistent and 
self-regulated 
positive self-esteem, 
with accurate self-
appraisal. 


Is capable of 
experiencing, 
tolerating, and 
regulating a full 
range of emotions. 


Has relatively intact 
sense of self, with 
some decrease in 
clarity of boundaries 
when strong 
emotions and mental 
distress are 
experienced. 


Self-esteem diminished 
at times, with overly 
critical or somewhat 
distorted self-
appraisal. 


Strong emotions may 
be distressing, 
associated with a 
restriction in range of 
emotional 
experience. 


Depends excessively 
on others for identity 


definition, with 


2 Moderate 


compromised 


impairment 


boundary 


delineation. 


Has vulnerable self-

Sets and aspires to 
reasonable goals 
based on a realistic 
assessment of 
personal capacities. 


Utilizes appropriate 
standards of 
behavior, attaining 
fulfillment in 
multiple realms. 


Can reflect on, and 
make constructive 
meaning of, internal 
experience. 


Is excessively goal-
directed, somewhat 
goal-inhibited, or 
conflicted about 
goals. 


May have an 
unrealistic or 
socially 
inappropriate set of 
personal standards, 
limiting some 
aspects of 
fulfillment. 


Is able to reflect on 
internal experiences, 
but may 
overemphasize a 
single (e.g., 
intellectual, 
emotional) type of 
self-knowledge. 


Goals are more often a 
means of gaining 
external approval 
than self-generated, 
and thus may lack 
coherence and/or 
stability. 


Is capable of accurately 
understanding others  
experiences and 
motivations in most 
situations. 


Comprehends and 
appreciates others  
perspectives, even if 
disagreeing. 


Is aware of the effect of 
own actions on others. 


Is somewhat compromised 
in ability to appreciate 
and understand others  
experiences; may tend to 
see others as having 
unreasonable 
expectations or a wish 
for control. 


Although capable of 
considering and 
understanding different 
perspectives, resists 
doing so. 


Has inconsistent awareness 
of effect of own behavior 
on others. 


Is hyperattuned to the 
experience of others, but 
only with respect to 
perceived relevance to 
self. 


Is excessively self-
referential; significantly 


Maintains multiple 
satisfying and enduring 
relationships in personal 
and community life. 


Desires and engages in a 
number of caring, close, 
and reciprocal 
relationships. 


Strives for cooperation and 
mutual benefit and flexibly 
responds to a range of 
others  ideas, emotions, 
and behaviors. 


Is able to establish enduring 
relationships in personal 
and community life, with 
some limitations on 
degree of depth and 
satisfaction. 


Is capable of forming and 
desires to form intimate 
and reciprocal 
relationships, but may be 
inhibited in meaningful 
expression and sometimes 
constrained if intense 
emotions or conflicts 
arise. 


Cooperation may be 
inhibited by unrealistic 
standards; somewhat 
limited in ability to respect 
or respond to others  ideas, 
emotions, and behaviors. 


Is capable of forming and 
desires to form 
relationships in personal 
and community life, but 
connections may be 
largely superficial. 


Intimate relationships are 



esteem controlled by 
Personal standards 
compromised ability to 
predominantly based on 
exaggerated concern 
may be 
appreciate and 
meeting self-regulatory 
about external 
unreasonably high 
understand others  
and self-esteem needs, 
evaluation, with a 
(e.g., a need to be 
experiences and to 
with an unrealistic 
wish for approval. 
special or please 
consider alternative 
expectation of being 
Has sense of 
others) or low (e.g., 
perspectives. 
perfectly understood by 


incompleteness or 
not consonant with 
Is generally unaware of or 
others. 


inferiority, with 
prevailing social 


unconcerned about effect 
Tends not to view 
compensatory 
values). Fulfillment 
of own behavior on 
relationships in reciprocal 


inflated, or deflated, 
is compromised by 


others, or unrealistic 
terms, and cooperates 
self-appraisal. 
a sense of lack of 
appraisal of own effect. 
predominantly for personal 


Emotional regulation 
authenticity. 
gain. 
depends on positive 
Has impaired capacity 
external appraisal. 
to reflect on internal 
Threats to self-experience. 
esteem may engender 
strong emotions such 
as rage or shame. 


897 
Has a weak sense of 
Has difficulty 
Ability to consider and 
Has some desire to form 
autonomy/agency; 
establishing and/or 
understand the thoughts, 
relationships in 
experience of a lack 
achieving personal 
feelings, and behavior of 
community and personal 


3 Severe 


of identity, or 
goals. 
other people is 
life, but capacity for 


impairment 


emptiness. Boundary 
significantly limited; 
positive and enduring 


Internal standards for 


definition is poor or 
may discern very 
connections is 


behavior are unclear 


rigid: may show 
specific aspects of 
significantly impaired. 


or contradictory. 


overidentification 
others  experience, 


Life is experienced 
Relationships are based on a 


with others, 
particularly 


as meaningless or 
strong belief in the 


overemphasis on 
vulnerabilities and 


dangerous. 
absolute need for the 


independence from 
suffering. 


intimate other(s), and/or 


Has significantly 


others, or vacillation 


Is generally unable to 
expectations of 


compromised ability 


between these. 


consider alternative 
abandonment or abuse. 


to reflect on and 


Fragile self-esteem is 
perspectives; highly 
Feelings about intimate 


understand own 


easily influenced by 
threatened by differences 
involvement with others 


mental processes. 


events, and self-of opinion or alternative 
alternate between 
image lacks 
viewpoints. 
fear/rejection and 
coherence. Self-desperate desire for 


Is confused about or 


appraisal is un-connection. 


unaware of impact of 


nuanced: self-

own actions on others; 
Little mutuality: others are 


loathing, self-

often bewildered about 
conceptualized primarily 


aggrandizing, or an 


people s thoughts and 
in terms of how they affect 


illogical, unrealistic 


actions, with destructive 
the self (negatively or 


combination. 


motivations frequently 
positively); cooperative 


Emotions may be 
misattributed to others. 
efforts are often disrupted 
rapidly shifting or a 
due to the perception of 
chronic, unwavering 
slights from others. 
feeling of despair. 


898 
Experience of a unique 
Has poor 
Has pronounced inability to 
Desire for affiliation is 
self and sense of 
differentiation of 
consider and understand 
limited because of 
agency/autonomy 
thoughts from 
others  experience and 
profound disinterest or 


4 Extreme 


are virtually absent, 
actions, so goal-motivation. 
expectation of harm. 


impairment 


or are organized 
setting ability is 
Engagement with others is 


Attention to others  


around perceived 
severely 
detached, disorganized, or 


perspectives is virtually 


external persecution. 
compromised, with 
consistently negative. 


absent (attention is 


Boundaries with 
unrealistic or 


hypervigilant, focused 
Relationships are 


others are confused 
incoherent goals. 


on need fulfillment and 
conceptualized almost 


or lacking. 


Internal standards for 
harm avoidance). 
exclusively in terms of 
Has weak or distorted 
behavior are 
their ability to provide 


Social interactions can be 


self-image easily 
virtually lacking. 
comfort or inflict pain and 


confusing and 


threatened by 
Genuine fulfillment 
suffering. 


disorienting. 


interactions with 
is virtually 


Social/interpersonal behavior 


others; significant 
inconceivable. 


is not reciprocal; rather, it 



distortions and 
confusion around 
self-appraisal. 


Emotions not congruent 
with context or 
internal experience. 
Hatred and 
aggression may be 
dominant affects, 
although they may be 
disavowed and 
attributed to others. 


Is profoundly unable to 
constructively 
reflect on own 
experience. Personal 
motivations may be 
unrecognized and/or 
experienced as 
external to self. 


seeks fulfillment of basic 
needs or escape from pain. 


899 


TABLE 
3 
Definitions 
of DSM-5 
personality 
disorder trait domains 
and 
facets 


DOMAINS (Polar 
Opposites) 
and 
Facets 
Definitions 


NEGATIVE AFFECTIVITY 
Frequent and intense experiences of high levels of a wide range of negative emotions (e.g., 
(vs. 
Emotional Stability) 
anxiety, depression, guilt/shame, worry, anger) and their behavioral (e.g., self-harm) and 
interpersonal (e.g., dependency) manifestations. 


Emotional lability 
Instability of emotional experiences and mood; emotions that are easily aroused, intense, and/or 
out of proportion to events and circumstances. 


Anxiousness 
Feelings of nervousness, tenseness, or panic in reaction to diverse situations; frequent worry 
about the negative effects of past unpleasant experiences and future negative possibilities; 
feeling fearful and apprehensive about uncertainty; expecting the worst to happen. 


Separation insecurity 
Fears of being alone due to rejection by and/or separation from significant others, based in a 
lack of confidence in one s ability to care for oneself, both physically and emotionally. 


Submissiveness 
Adaptation of one s behavior to the actual or perceived interests and desires of others even when 
doing so is antithetical to one s own interests, needs, or desires. 


Hostility 
Persistent or frequent angry feelings; anger or irritability in response to minor slights and 
insults; mean, nasty, or vengeful behavior. See also Antagonism. 


Perseveration 
Persistence at tasks or in a particular way of doing things long after the behavior has ceased to 
be functional or effective; continuance of the same behavior despite repeated failures or clear 
reasons for stopping. 


Depressivity 
See Detachment. 


Suspiciousness 
See Detachment. 


Restricted affectivity (lack of) 
The lack of this facet characterizes low levels of Negative Affectivity. See Detachment for 
definition of this facet. 


DETACHMENT 
(vs. 
Avoidance of socioemotional experience, including both withdrawal from interpersonal 
Extraversion) 
interactions (ranging from casual, daily interactions to friendships to intimate relationships) 
and restricted affective experience and expression, particularly limited hedonic capacity. 


Withdrawal 
Preference for being alone to being with others; reticence in social situations; avoidance of 
social contacts and activity; lack of initiation of social contact. 


Intimacy avoidance 
Avoidance of close or romantic relationships, interpersonal attachments, and intimate sexual 
relationships. 


Anhedonia 
Lack of enjoyment from, engagement in, or energy for life s experiences; deficits in the capacity 
to feel pleasure and take interest in things. 


Depressivity 
Feelings of being down, miserable, and/or hopeless; difficulty recovering from such moods; 
pessimism about the future; pervasive shame and/or guilt; feelings of inferior self-worth; 
thoughts of suicide and suicidal behavior. 


Restricted affectivity 
Little reaction to emotionally arousing situations; constricted emotional experience and 


expression; indifference and aloofness in normatively engaging situations. 



Suspiciousness 
Expectations of and sensitivity to signs of interpersonal ill-intent or harm; doubts about 
loyalty and fidelity of others; feelings of being mistreated, used, and/or persecuted by others. 


900 


Behaviors that put the individual at odds with other people, including an exaggerated sense of 
self-importance and a concomitant expectation of special treatment, as well as a callous 
antipathy toward others, encompassing both an unawareness of others  needs and feelings and 


ANTAGONISM 
(vs. 


a readiness to use others in the service of self-enhancement. 


Agreeableness) 


Manipulativeness 
Use of subterfuge to influence or control others; use of seduction, charm, glibness, or 
ingratiation to achieve one s ends. 


Deceitfulness 
Dishonesty and fraudulence; misrepresentation of self; embellishment or fabrication when 
relating events. 


Grandiosity 
Believing that one is superior to others and deserves special treatment; self-centeredness; 
feelings of entitlement; condescension toward others. 


Attention seeking 
Engaging in behavior designed to attract notice and to make oneself the focus of others  
attention and admiration. 


Callousness 
Lack of concern for the feelings or problems of others; lack of guilt or remorse about the 
negative or harmful effects of one s actions on others. 


Hostility 
See Negative Affectivity. 


DISINHIBITION (vs. 
Orientation toward immediate gratification, leading to impulsive behavior driven by current 
Conscientiousness) 
thoughts, feelings, and external stimuli, without regard for past learning or consideration of 
future consequences. 


Irresponsibility 
Disregard for and failure to honor financial and other obligations or commitments; lack of 
respect for and lack of follow-through on agreements and promises; carelessness with 
others  property. 


Impulsivity 
Acting on the spur of the moment in response to immediate stimuli; acting on a momentary 
basis without a plan or consideration of outcomes; difficulty establishing and following plans; 
a sense of urgency and self-harming behavior under emotional distress. 


Distractibility 
Difficulty concentrating and focusing on tasks; attention is easily diverted by extraneous stimuli; 
difficulty maintaining goal-focused behavior, including both planning and completing tasks. 


Risk taking 
Engagement in dangerous, risky, and potentially self-damaging activities, unnecessarily and 
without regard to consequences; lack of concern for one s limitations and denial of the reality 
of personal danger; reckless pursuit of goals regardless of the level of risk involved. 


Rigid perfectionism (lack of) 
Rigid insistence on everything being flawless, perfect, and without errors or faults, including 
one s own and others  performance; sacrificing of timeliness to ensure correctness in every 
detail; believing that there is only one right way to do things; difficulty changing ideas and/or 
viewpoint; preoccupation with details, organization, and order. The lack of this facet 
characterizes low levels of Disinhibition. 


901 
Exhibiting a wide range of culturally incongruent odd, eccentric, or unusual behaviors and 
cognitions, including both process (e.g., perception, dissociation) and content (e.g., beliefs). 


PSYCHOTICISM 
(vs. 
Lucidity) 


Unusual beliefs and 
Belief that one has unusual abilities, such as mind reading, telekinesis, thought-action fusion; 
experiences 
unusual experiences of reality, including hallucination-like experiences. 


Eccentricity 
Odd, unusual, or bizarre behavior, appearance, and/or speech; having strange and unpredictable 
thoughts; saying unusual or inappropriate things. 


Cognitive and perceptual 
Odd or unusual thought processes and experiences, including depersonalization, derealization, 
dysregulation 
and dissociative experiences; mixed sleep-wake state experiences; thought-control 
experiences. 


902 



903 



Conditions for Further Study 


Proposed criteria sets 
are presented for conditions on which future research is 
encouraged. It 
is hoped that 
such research will 
allow the field to better understand these 
conditions and inform 
future decisions about 
possible placement 
in forthcoming editions of 
DSM. Notably, persistent 
complex bereavement 
disorder, originally located in this section, has 
been moved to the chapter  Trauma- and Stressor-Related Disorders  as an official 
diagnosis in 
Section II. On the basis of thorough reviews finding sufficient 
evidence of validity, reliability, 
and clinical 
utility to justify its new placement, it 
is now named  prolonged grief disorder  and 
the criteria have been appropriately reformulated. 


The specific items, thresholds, and minimum 
durations contained in these research criteria 
sets were set 
by expert 
consensus informed by literature review, data reanalysis, and field trial 
results, where available and are intended to provide a common language for researchers and 
clinicians who are interested in studying these disorders. The DSM-5 Task Force and Work 
Groups subjected each of these proposed criteria sets to a careful 
empirical 
review and invited 
wide commentary from 
the field as well 
as from 
the general 
public. The Task Force ultimately 
determined that 
there was insufficient 
evidence to warrant 
inclusion of these proposals as official 
mental 
disorder diagnoses in Section II of DSM-5. These proposed criteria sets are therefore 
not 
intended for clinical 
use; only the criteria sets and disorders in 
Section 
II of DSM-5 are 
officially recognized and should be used for clinical purposes. 


Attenuated 
Psychosis Syndrome 


Proposed Criteria 


A. 
At 
least 
one 
of 
the 
following 
symptoms is present 
and 
is of 
sufficient 
severity or 
frequency to 
warrant 
clinical attention: 
1. 
Attenuated 
delusions. 
2. 
Attenuated 
hallucinations. 
3. 
Attenuated 
disorganized 
speech. 
B. 
Symptom(s) must 
have 
been 
present 
at 
least 
once 
per week for the 
past 
month. 
C. 
Symptom(s) must 
have 
begun 
or worsened 
in 
the 
past 
year. 
D. 
Symptom(s) is sufficiently distressing 
and 
disabling 
to 
the 
individual to 
warrant 
clinical attention. 
E. 
Symptom(s) is not 
better explained 
by another mental disorder, 
including 
a 
depressive 
or bipolar disorder with 
psychotic features, 
and 
is not 
attributable 
to 

the 
physiological effects of 
a 
substance 
or another medical condition. 


F. 
Criteria 
for any psychotic disorder have 
never been 
met. 
904 


Diagnostic Features 


Attenuated psychotic symptoms, as defined in Criterion A, are psychosis-like but 
below the 
threshold to be considered a psychotic symptom 
that 
would count 
toward the diagnosis of a 
psychotic disorder. Compared with full 
psychotic disorders, the symptoms are less severe and 
more transient. Moreover, the individual 
maintains reasonable insight 
into the psychotic-like 
experiences and generally appreciates that 
perceptions are altered, and magical 
ideation is not 
compelling. Attenuated psychosis does not 
have the fixed nature that 
is necessary for the 
diagnosis of a full-blown psychotic disorder. In attenuated psychosis, doubt 
about 
beliefs can be 
elicited, skepticism 
about 
perceptions can be induced, and insight 
can be tested using open-ended 
questions, such as  I see that 
this is how you experience the world could there be a different 
explanation?  A diagnosis of attenuated psychosis syndrome requires state psychopathology 
associated with functional 
impairment 
rather than long-standing trait 
pathology. The 
psychopathology has not 
progressed to full 
psychotic severity. Changes in experiences and 
behaviors are noted by the individual 
or others, suggesting a clinically significant 
change in 
mental 
state (i.e., the symptoms are of sufficient 
severity or frequency to warrant 
clinical 
attention) (Criterion A). 


Attenuated delusions (Criterion A1) may have suspiciousness/persecutory ideational 
content, 
including persecutory ideas of reference. The individual 
may have a guarded, distrustful 
attitude. 
When this type of attenuated delusion is moderate in severity, the individual 
views others as 
untrustworthy and may be hypervigilant 
or sense ill 
will 
in others. When the attenuated delusions 
are severe but 
below the threshold to be considered psychotic, the individual 
entertains loosely 
organized beliefs about 
danger or hostile intention. Guarded behavior in the interview can 
interfere with the ability to gather information, and the propensity for viewing the world as 
hostile and dangerous is strong. On the other hand, attenuated delusions may have grandiose 
content 
presenting as an unrealistic sense of superior capacity. When this type of attenuated 
delusion is moderate in severity, the individual 
harbors notions of being gifted, influential, or 
special. When the attenuated delusions are severe, the individual 
has beliefs of superiority that 
often alienate friends and worry relatives. Thoughts of being special 
may lead to unrealistic plans 
and investments. 


Attenuated hallucinations (Criterion A2) include alterations in sensory perceptions, usually 
auditory and/or visual. When the attenuated hallucinations are moderate, the sounds and images 
are often unformed (e.g., shadows, trails, halos, murmurs, rumbling), and they are experienced as 
unusual 
or puzzling. When the attenuated hallucinations are severe, these experiences become 
more vivid and frequent 
(i.e., recurring illusions or hallucinations that 
capture attention and 
affect 
thinking and concentration). These perceptual 
abnormalities may disrupt 
behavior, but 
skepticism about their reality can still be induced. 


Attenuated disorganized communication (Criterion A3) may manifest 
as odd speech (vague, 
metaphorical, overelaborate, stereotyped), unfocused speech (confused, muddled, too fast 
or too 
slow, wrong words, irrelevant 
context, off track), or meandering speech (circumstantial, 



tangential). When the disorganization is moderately severe, the individual 
frequently gets into 
irrelevant 
topics but 
responds easily to clarifying questions. Speech becomes meandering and 
circumstantial 
and may be odd but 
understandable. When the disorganization is severe, the 
individual 
fails to get 
to the point 
without 
external 
guidance (tangential). At 
a more severe level, 
some thought 
blocking or loose associations may occur infrequently, especially when the 
individual 
is under pressure, but 
reorienting questions quickly return structure and organization 
to the conversation. 


The individual 
must 
experience distress and/or impaired performance in social 
or role 
functioning (Criterion D), and the individual 
or responsible others must 
note the changes and 
express concern, such that clinical care is indicated (Criterion A). 


905 


Measures are available to determine whether Criteria A E 
are met 
or to broadly identify a 
clinical high-risk state for psychosis. 


Associated Features 


The individual 
may experience magical 
thinking, difficulty in concentration, some 
disorganization in thought 
or behavior, excessive suspiciousness, anxiety, social 
withdrawal, and 
disruption in sleep-wake cycle. Impaired cognitive function and negative symptoms are often 
observed. 


Neuroimaging variables distinguish cohorts with attenuated psychosis syndrome from normal 
control 
cohorts with patterns similar to, but 
less severe than, that 
observed in schizophrenia. 
However, neuroimaging data are not diagnostic at the individual level. 


Prevalence 


Very little information is available about 
prevalence. However, in Switzerland, where one of the 
few relevant 
studies was conducted, the prevalence of attenuated psychosis syndrome in non-
help-seeking individuals ages 16 40 years was found to be only 0.3%. Another 2.3% have 
attenuated symptoms that 
meet 
Criterion A, but 
these symptoms either began prior to the past 
year or had not 
worsened in the past 
year, as required by Criterion C. In up to 7% of the general 
population across a broad range of countries, individuals acknowledge experiencing attenuated 
delusions or hallucinations. While the prevalence of Criterion A symptoms can be higher or 
lower across countries or ethnonational 
groups, the prevalence of attenuated psychosis symptoms 
tends to be higher among migrant 
groups than among native populations, possibly due to higher 
exposure to trauma and discrimination. 


Development and Course 


Onset 
of attenuated psychosis syndrome is usually in mid-to-late adolescence or early adulthood. 
It 
may be preceded by normal 
development 
or evidence for impaired cognition, negative 
symptoms, or impaired social 
development. In help-seeking cohorts, those whose presentations 
met 
criteria for attenuated psychosis syndrome had an increased probability of developing 
psychosis compared with those whose presentations did not 
meet 
the criteria. In the group whose 
presentations met 
criteria, the 3-year cumulative risk was up to 22%, and in the group whose 



presentations did not 
meet 
criteria, the 3-year cumulative risk of psychosis was 1.54%. Factors 
predicting progression to a full 
psychotic disorder (most 
frequently schizophrenia spectrum 
disorder) include male sex, lifetime stress/trauma, unemployment, living alone, severity of 
attenuated positive psychotic symptoms, severity of negative symptoms, disorganized and 
cognitive symptoms, and poor functioning. Eleven percent 
of those attenuated psychosis 
syndrome cases that 
progress to full 
psychosis develop affective psychosis (depressive or bipolar 
disorder with psychotic features), whereas 73% of attenuated psychosis syndrome cases that 
progress to full 
psychosis develop a schizophrenia spectrum 
disorder. Most 
evidence has 
validated attenuated psychotic symptom criteria in individuals ages 12 35 years, but there is only 
limited evidence in the youngest. Although the highest 
risk for transition to psychosis is within 
the first 
2 years, individuals continue to be at 
risk for up to 10 years after initial 
referral, with an 
overall 
risk of transition of 34.9% over a 10-year period. Individuals presenting with attenuated 
psychosis syndrome may display other poor clinical 
outcomes beyond the development 
of 
psychosis, such as persistent 
attenuated psychotic symptoms, persistent 
or recurrent 
comorbid 
mental 
disorders, disability, and low functioning. Clinical 
remission is present 
in only one-third 
of individuals with attenuated psychosis syndrome. Overall, about 
one-third of these individuals 
would develop psychosis, one-third would remit, and one-third would present 
persistent 
disability. 


906 


Risk and Prognostic Factors 


Temperamental. 
Factors predicting prognosis of attenuated psychosis syndrome have not 
been 


definitively characterized. 
Genetic 
and 
physiological. 
In individuals whose symptoms meet 
criteria for attenuated psychosis 
syndrome, there is no evidence that 
a family history of psychosis increases the risk of psychosis 
compared with control 
subjects over a 4-year period. Structural, functional, electrophysiological, 
and neurochemical 
imaging data are associated with increased risk of transition to psychosis. 
However, these predictors have not yet been validated for clinical use. 


Culture-Related Diagnostic Issues 


Assessing the presence of attenuated symptoms without 
considering the impact 
of sociocultural 
context 
can be difficult. Some perceptual 
experiences (e.g., hearing noises, seeing shadows) and 
religious or supernatural 
beliefs (e.g., evil 
eye, causing illness through curses, influence of 
spirits) may be considered odd in some cultural 
contexts and accepted in others. In addition, 
populations that 
experience trauma or persecution (e.g., torture, political 
violence, racism, 
discrimination) can report 
symptoms and fears that 
may be misjudged as attenuated or frank 
paranoid delusions, because of the impact 
of trauma on the individual s mood and 
communication (e.g., some fears may be appropriate to avoid threats, and may commingle with 
fears of recurrence of trauma or posttraumatic symptoms). Groups at 
higher risk of misdiagnosis 
include migrants, socially oppressed ethnic and racialized populations, and other groups facing 
social 
adversity and discrimination. The distress and impairment 
criterion helps to distinguish 
socioculturally normative experiences from 
symptoms of attenuated psychosis syndrome (e.g., 
adaptive wariness toward authority figures by discriminated groups, which may be confused with 



paranoia). 


Functional 
Consequences of Attenuated Psychosis Syndrome 


Many individuals may experience functional 
impairments at 
presentation. Modest-to-moderate 
impairment in social and role functioning may persist even with abatement of symptoms. 


Differential 
Diagnosis 


Brief 
psychotic 
disorder. 
When symptoms of attenuated psychosis syndrome initially manifest, 
they may resemble symptoms of brief psychotic disorder. However, in attenuated psychosis 
syndrome, the attenuated symptoms (delusions, hallucinations, or disorganized speech) do not 
cross the psychosis threshold. 


Schizotypal 
personality 
disorder. 
Symptomatic features of schizotypal 
personality disorder, 
particularly during early stages of presentation, are similar to those of attenuated psychosis 
syndrome. However, schizotypal 
personality disorder is a relatively stable trait 
disorder not 
meeting the state-dependent 
aspects (Criterion C) of attenuated psychosis syndrome. In addition, 
a broader array of symptoms is required for the diagnosis of schizotypal personality disorder. 
Reality 
distortions 
occurring 
in 
other mental 
disorders. 
Reality distortions that 
can resemble 


attenuated delusions can occur in the context 
of other mental 
disorders (e.g., feelings of low self-
esteem 
or attributions of low regard from 
others in the context 
of major depressive disorder, a 
feeling of being the focus of undesired attention in the context 
of social 
anxiety disorder, inflated 
self-esteem 
in the context 
of pressured speech and reduced need for sleep in bipolar I or bipolar 
II disorder, a sense of being unable to experience feelings in the context 
of an intense fear of real 
or imagined abandonment 
and recurrent 
self-mutilation in borderline personality disorder). If 
these reality distortions occur only during 


907 


the course of another mental 
disorder, an additional 
diagnosis of attenuated psychosis syndrome 


would not be made. 
Adjustment 
reaction 
of 
adolescence. 
Mild, transient 
symptoms typical 
of normal 
development 
and 
consistent 
with the degree of stress experienced do not 
qualify for attenuated psychosis 
syndrome. 
Extreme 
end 
of 
perceptual 
aberration 
and 
magical 
thinking 
in 
the 
non-ill 
population. 
This diagnostic 


possibility should be strongly entertained when reality distortions are not 
associated with distress 
and functional impairment and need for care. 


Substance/medication-induced 
psychotic 
disorder. 


Attenuated delusions and attenuated 
hallucinations can occur in the context 
of intoxication with cannabis, hallucinogens, 
phencyclidine, inhalants, and stimulants, or during withdrawal 
from 
alcohol 
and sedatives, 
hypnotics, or anxiolytics. Attenuated psychosis syndrome should not 
be diagnosed if the 
attenuated psychotic symptoms occur only during substance use, in which case a diagnosis of 
substance/medication-induced psychotic disorder may be preferred. 


Attention-deficit/hyperactivity 
disorder. 
A history of attentional 
impairment 
does not 
exclude a 
current 
attenuated psychosis syndrome diagnosis. Earlier attentional 
impairment 
may be a 



prodromal condition or comorbid attention-deficit/hyperactivity disorder. 


Comorbidity 


Most 
individuals with attenuated psychosis syndrome experience some comorbid mental 
disorder, mostly depression (41%) and/or anxiety (15%). A little more than half of individuals 
have at 
least 
one comorbid disorder at 
follow-up, most 
of which were present 
when the 
individual 
was first 
assessed; 
the persistence of comorbid disorders at 
follow-up is associated 
with poor clinical 
and functional 
outcomes. Although some individuals with an attenuated 
psychosis syndrome diagnosis will 
progress to developing a new diagnosis, including anxiety, 
depressive, bipolar, and personality disorders, individuals with 
attenuated psychosis syndrome 
are not 
at 
increased risk of developing new nonpsychotic disorders compared with help-seeking 
control subjects. 


Depressive Episodes With 
Short-Duration 
Hypomania 


Proposed Criteria 


Lifetime 
experience 
of at least one 
major depressive 
episode 
meeting 
the 
following 
criteria: 


A. 
Five 
(or more) of 
the 
following 
criteria 
have 
been 
present 
during 
the 
same 
2week 
period 
and 
represent 
a 
change 
from previous functioning; 
at 
least 
one 
of 
the 
symptoms is either (1) depressed 
mood 
or (2) loss of 
interest 
or pleasure. 
(Note: 
Do 
not 
include 
symptoms that 
are 
clearly attributable 
to 
a 
medical 
condition.) 
1. 
Depressed 
mood 
most 
of 
the 
day, 
nearly every day, 
as indicated 
by either 
subjective 
report 
(e.g., 
feels sad, 
empty, 
or hopeless) or observation 
made 
by 
others (e.g., 
appears tearful). 
(Note: 
In 
children 
and 
adolescents, 
can 
be 
irritable 
mood.) 
2. 
Markedly diminished 
interest 
or pleasure 
in 
all, 
or almost 
all, 
activities most 
of 
the 
day, 
nearly every day (as indicated 
by either subjective 
account 
or 
observation). 
3. 
Significant 
weight 
loss when 
not 
dieting 
or weight 
gain 
(e.g., 
a 
change 
of 
more 
than 
5% of 
body weight 
in 
a 
month), 
or decrease 
or increase 
in 
appetite 
nearly every day. 
(Note: 
In 
children, 
consider failure 
to 
make 
expected 
weight 
gain.) 
908 


4. 
Insomnia 
or hypersomnia 
nearly every day. 
5. 
Psychomotor agitation 
or retardation 
nearly every day (observable 
by others, 
not 
merely subjective 
feelings of 
restlessness or being 
slowed 
down). 

6. 
Fatigue 
or loss of 
energy nearly every day. 
7. 
Feelings of 
worthlessness or excessive 
or inappropriate 
guilt 
(which 
may be 
delusional) nearly every day (not 
merely self-reproach 
or guilt 
about 
being 
sick). 
8. 
Diminished 
ability to 
think or concentrate, 
or indecisiveness, 
nearly every day 
(either by subjective 
account 
or as observed 
by others). 
9. 
Recurrent 
thoughts of 
death 
(not 
just 
fear of 
dying), 
recurrent 
suicidal ideation 
without 
a 
specific plan, 
or a 
suicide 
attempt 
or a 
specific plan 
for committing 
suicide. 
B. 
The 
symptoms cause 
clinically significant 
distress or impairment 
in 
social, 
occupational, 
or other important 
areas of 
functioning. 
C. 
The 
disturbance 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
or 
another medical condition. 
D. 
The 
disturbance 
is not 
better explained 
by schizoaffective 
disorder and 
is not 
superimposed 
on 
schizophrenia, 
schizophreniform disorder, 
delusional disorder, 
or other specified 
or unspecified 
schizophrenia 
spectrum and 
other psychotic 
disorder. 
At least two 
lifetime 
episodes 
of hypomanic 
periods 
that involve 
the 
required 
criterion 
symptoms 
below 
but are 
of insufficient duration 
(at least 2 
days 
but 
less 
than 
4 
consecutive 
days) to 
meet criteria 
for a 
hypomanic 
episode. 
The 
criterion 
symptoms 
are 
as 
follows: 


A. 
A 
distinct 
period 
of 
abnormally and 
persistently elevated, 
expansive, 
or irritable 
mood 
and 
abnormally and 
persistently increased 
activity or energy. 
B. 
During 
the 
period 
of 
mood 
disturbance 
and 
increased 
energy and 
activity, 
three 
(or more) of 
the 
following 
symptoms have 
persisted 
(four if 
the 
mood 
is only 
irritable), 
represent 
a 
noticeable 
change 
from usual behavior, 
and 
have 
been 
present 
to 
a 
significant 
degree: 
1. 
Inflated 
self-esteem or grandiosity. 
2. 
Decreased 
need 
for sleep 
(e.g., 
feels rested 
after only 3 
hours of 
sleep). 
3. 
More 
talkative 
than 
usual or pressured 
to 
keep 
talking. 
4. 
Flight 
of 
ideas or subjective 
experience 
that 
thoughts are 
racing. 
5. 
Distractibility (i.e., 
attention 
too 
easily drawn 
to 
unimportant 
or irrelevant 
external stimuli), 
as reported 
or observed. 
6. 
Increase 
in 
goal-directed 
activity (either socially, 
at 
work or school, 
or 
sexually) or psychomotor agitation. 
7. 
Excessive 
involvement 
in 
activities that 
have 
a 
high 
potential for painful 
consequences (e.g., 
the 
individual engages in 
unrestrained 
buying 
sprees, 
sexual indiscretions, 
or foolish 
business investments). 
C. 
The 
episode 
is associated 
with 
an 
unequivocal change 
in 
functioning 
that 
is 
uncharacteristic of 
the 
individual when 
not 
symptomatic. 
D. 
The 
disturbance 
in 
mood 
and 
the 
change 
in 
functioning 
are 
observable 
by 

others. 


E. 
The 
episode 
is not 
severe 
enough 
to 
cause 
marked 
impairment 
in 
social or 
occupational functioning 
or to 
necessitate 
hospitalization. 
If 
there 
are 
psychotic 
features, 
the 
episode 
is, 
by definition, 
manic. 
F. 
The 
episode 
is not 
attributable 
to 
the 
physiological effects of 
a 
substance 
(e.g., 
a 
drug 
of 
abuse, 
a 
medication 
or other treatment). 
909 


Diagnostic Features 


Individuals with depressive episodes with short-duration hypomania have experienced at 
least 
one major depressive episode as well 
as at 
least 
two episodes of 2 3 days  duration in which 
criteria for a hypomanic episode were met 
(except 
for symptom 
duration). These episodes are of 
sufficient 
intensity to be categorized as a hypomanic episode but 
do not 
meet 
the 4-day duration 
requirement. Symptoms are present 
to a significant 
degree, such that 
they represent 
a noticeable 
change from the individual s normal behavior. 


An individual 
with a history of a syndromal 
hypomanic episode and a major depressive 
episode by definition has bipolar II disorder, regardless of current 
duration of hypomanic 
symptoms. 


Associated Features 


Individuals who have experienced both short-duration hypomania and a major depressive 
episode, with their increased psychiatric comorbidity, greater family history of bipolar disorder, 
earlier onset, more recurrent 
major depressive episodes, and higher rate of suicide attempts, more 
closely resemble individuals with bipolar disorder than those with major depressive disorder. 


Prevalence 


The prevalence of depressive episodes with short-duration hypomania is unclear, as 
epidemiological 
studies have yet 
to be published using the DSM-5 definition. Using somewhat 
different 
criteria (subthreshold hypomania defined by either of the following: 
duration shorter 
than 4 days or having fewer than three Criterion B 
symptoms), major depressive disorder with 
subthreshold hypomania occurs in up to 6.7% of the U.S. population, making it 
more common 
than bipolar I or II disorder. In clinical 
settings studied across diverse countries, however, 
depressive episodes with short-duration hypomania is about 
one-fourth as common as depressive 
episodes with full-duration hypomania. Depressive episodes with short-duration hypomania may 
be more common in women, who may present with more features of atypical depression. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
A family history of bipolar disorder is three to four times more 
common among individuals with depressive episodes with short-duration hypomania than among 
those with major depressive disorder, whereas family history of bipolar disorder is similar among 
individuals with depressive episodes and short- versus full-duration hypomania. 



Association With Suicidal 
Thoughts or Behavior 


Individuals with depressive episodes with short-duration hypomania have higher rates of suicide 
attempts than individuals with major depressive disorder and similar rates of suicide attempts 
compared with individuals with depressive episodes and full-duration hypomania (bipolar II 
disorder). 


Functional 
Consequences of Short-Duration Hypomania 


Functional 
impairments associated specifically with depressive episodes with short-duration 
hypomania are as yet 
not 
fully determined. However, research suggests that 
individuals with this 
disorder have similar global 
assessment 
of functioning scores as compared to those with 
depressive episodes with full-duration hypomania. 


910 


Differential 
Diagnosis 


Bipolar II 
disorder. 
Bipolar II disorder is characterized by major depressive episodes and 
hypomanic episodes, whereas depressive episodes with short-duration hypomania are 
characterized by depressive episodes with periods of 2 3 days of hypomanic symptoms. Once an 
individual 
has experienced a full-blown hypomanic episode lasting 4 days or more in addition to 
lifetime major depressive episodes, the diagnosis changes to and remains bipolar II disorder 
regardless of the duration of future hypomanic symptom periods. 


Major depressive 
disorder. 
Major depressive disorder is also characterized by at 
least 
one lifetime 
major depressive episode. However, the additional 
presence of at 
least 
two lifetime periods of 2  
3 days of hypomanic symptoms leads to a diagnosis of depressive episodes with short-duration 
hypomania rather than to major depressive disorder. 


Major depressive 
disorder with 
mixed 
features. 
Both major depressive disorder with mixed features 
and depressive episodes with short-duration hypomania are characterized by the presence of 
some hypomanic symptoms and a major depressive episode. However, major depressive disorder 
with mixed features is characterized by hypomanic features that 
manifest 
concurrently 
with a 
major depressive episode, whereas individuals with depressive episodes with short-duration 
hypomania experience subsyndromal 
hypomania and fully syndromal 
major depression at 
different times. 


Bipolar I 
disorder. 
Bipolar I disorder is differentiated from 
depressive episodes with short-
duration hypomania by at 
least 
one lifetime manic episode, which is longer (at 
least 
1 week) and 
more severe (causing marked impairment 
in social 
or occupational 
functioning or necessitating 
hospitalization to prevent 
harm 
to self and others) than a hypomanic episode. An episode (of any 
duration) that 
involves psychotic symptoms or necessitates hospitalization is by definition a 
manic episode rather than a hypomanic one. 


Cyclothymic 
disorder. 
While cyclothymic disorder is characterized by periods of depressive 
symptoms and periods of hypomanic symptoms, the lifetime presence of a major depressive 
episode precludes the diagnosis of cyclothymic disorder. 



Caffeine Use Disorder 


Proposed Criteria 


A 
problematic pattern 
of 
caffeine 
use 
leading 
to 
clinically significant 
impairment 
or 
distress, 
as manifested 
by at 
least 
the 
first 
three 
of 
the 
following 
criteria 
occurring 
within 
a 
12-month 
period: 


1. 
A 
persistent 
desire 
or unsuccessful efforts to 
cut 
down 
or control caffeine 
use. 
2. 
Continued 
caffeine 
use 
despite 
knowledge 
of 
having 
a 
persistent 
or recurrent 
physical or psychological problem that 
is likely to 
have 
been 
caused 
or 
exacerbated 
by caffeine. 
3. 
Withdrawal, 
as manifested 
by either of 
the 
following: 
a. 
The 
characteristic withdrawal syndrome 
for caffeine. 
b. 
Caffeine 
(or a 
closely related 
substance) is taken 
to 
relieve 
or avoid 
withdrawal symptoms. 
4. 
Caffeine 
is often 
taken 
in 
larger amounts or over a 
longer period 
than 
was 
intended. 
5. 
Recurrent 
caffeine 
use 
resulting 
in 
a 
failure 
to 
fulfill major role 
obligations at 
work, 
school, 
or home 
(e.g., 
repeated 
tardiness or absences from work or school 
related 
to 
caffeine 
use 
or withdrawal). 
6. 
Continued 
caffeine 
use 
despite 
having 
persistent 
or recurrent 
social or 
interpersonal problems caused 
or exacerbated 
by the 
effects of 
caffeine 
(e.g., 
arguments with 
spouse 
about 
consequences of 
use, 
medical problems, 
cost). 
911 


7. 
Tolerance, 
as defined 
by either of 
the 
following: 
a. 
A 
need 
for markedly increased 
amounts of 
caffeine 
to 
achieve 
desired 
effect. 
b. 
Markedly diminished 
effect 
with 
continued 
use 
of 
the 
same 
amount 
of 
caffeine. 
8. 
A 
great 
deal of 
time 
is spent 
in 
activities necessary to 
obtain 
caffeine, 
use 
caffeine, 
or recover from its effects. 
9. 
Craving 
or a 
strong 
desire 
or urge 
to 
use 
caffeine. 
Various research studies have provided documentation and characterization of individuals 
with problematic caffeine use, and several 
reviews provide an analysis of this literature. The 
working diagnostic algorithm 
proposed for the study of caffeine use disorder differs from 
that 
of 
the other substance use disorders, reflecting the need to identify only cases that 
have sufficient 
clinical 
importance to warrant 
the labeling of a mental 
disorder. A key goal 
of including caffeine 
use disorder in this section of DSM-5 is to stimulate research that 
will 
determine the reliability, 
validity, and prevalence of caffeine use disorder based on the proposed diagnostic schema, with 
particular attention to the association of the diagnosis with functional 
impairments as part 
of 
validity testing. 



The proposed criteria for caffeine use disorder reflect 
the need for a diagnostic threshold 
higher than that 
used for the other substance use disorders. Such a threshold is intended to 
prevent 
overdiagnosis of caffeine use disorder due to the high rate of habitual 
nonproblematic 
daily caffeine use in the general population. 


Diagnostic Features 


Caffeine use disorder is characterized by the continued use of caffeine and failure to control 
use 
despite negative physical 
and/or psychological 
consequences. In two U.S. population surveys, 
14% 17% of caffeine users endorsed caffeine use despite physical 
or psychological 
problems, 
34% 45% reported a persistent 
desire or unsuccessful 
efforts to control 
caffeine use, and 18%  
27% reported withdrawal 
or using caffeine to relieve or avoid withdrawal. In these same surveys, 
some caffeine users reported using more caffeine than intended, spending a great 
deal 
of time 
using or obtaining caffeine (e.g., drinking coffee all 
day and until 
the evening), tolerance, a 
strong desire or craving for caffeine, failure to fulfill 
major role obligations due to caffeine (e.g., 
spending family vacation time searching for caffeinated beverages, resulting in relationship 
distress; 
repeatedly late for work due to need to get 
coffee), and, to a much lesser extent, caffeine 
use despite social 
or interpersonal 
problems. Medical 
and psychological 
problems attributed to 
caffeine included heart, stomach, and urinary problems, and complaints of anxiety, depression, 
insomnia, irritability, and difficulty thinking. 


In a study of 2,259 Hungarian caffeine consumers, factor analysis of the nine caffeine use 
disorder criteria resulted in a one-factor solution, suggesting that 
caffeine use disorder is a 
unitary construct. In two Baltimore-area caffeine treatment 
studies, the most 
commonly endorsed 
criteria were withdrawal 
(97%), persistent 
desire or unsuccessful 
efforts to control 
use (91%  
94%), and use despite knowledge of physical 
or psychological 
problems caused by caffeine 
(75% 91%). 


Among individuals seeking treatment 
for problematic caffeine use, 88% reported having 
made prior serious attempts to modify caffeine use, and 43% 47% reported having been advised 
by a medical 
professional 
to reduce or eliminate caffeine. Common reported reasons for 
modifying caffeine use were health-related (59%) and a desire to not 
be dependent 
on caffeine 
(35%). 


The text 
for caffeine withdrawal 
in the Section II chapter  Substance-Related and Addictive 
Disorders  provides information on the features of the withdrawal 
criterion. It 
is well 
documented that 
habitual 
caffeine users can experience a well-defined withdrawal 
syndrome 
upon acute abstinence from 
caffeine, and many caffeine-dependent 
individuals report 
continued 
use of caffeine to avoid experiencing withdrawal symptoms. 


912 


Prevalence 


The prevalence of caffeine use disorder in the general 
population is unclear. One population-
based study in Vermont 
reported that 
9% of individuals endorsed the three proposed DSM-5 
caffeine use disorder criteria plus tolerance. In a sample of 1,006 caffeine-consuming adults 
recruited using demographic quotas to reflect 
the U.S. population, 8% endorsed all 
three criteria 
required for a caffeine use disorder diagnosis. 



In a sample of caffeine-consuming adolescents presenting for routine medical 
care in a 
Boston hospital, 3.9% endorsed all 
three criteria required for a caffeine use disorder diagnosis. 
Among a convenience sample of caffeine consumers in Hungary, 13.9% endorsed all 
three 
criteria, with 4.3% of those reporting that 
the symptoms caused significant 
distress in their 
everyday life. 


Development and Course 


Individuals whose pattern of use meets criteria for a caffeine use disorder have shown a wide 
range of daily caffeine intake and have been consumers of various types of caffeinated products 
(e.g., coffee, soft 
drinks, tea, energy drinks) and medications. A diagnosis of caffeine use 
disorder has been shown to prospectively predict 
a greater incidence of caffeine reinforcement 
and more severe withdrawal. 


There has been no longitudinal 
or cross-sectional 
lifespan research on caffeine use disorder. 
Caffeine use disorder has been identified in both adolescents and adults. Rates of caffeine 
consumption and overall 
level 
of caffeine consumption in the United States tend to increase with 
age. Age-related factors for caffeine use disorder are unknown, although concern is growing 
related to excessive caffeine consumption among adolescents and young adults through use of 
caffeinated energy drinks. 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
Heritabilities of heavy caffeine use, caffeine tolerance, and caffeine 
withdrawal 
range from 
35% to 77%. For caffeine use, alcohol 
use, and cigarette smoking, a 
common genetic factor (polysubstance use) underlies the use of these three substances, with 
28% 41% of the heritable effects of caffeine use (or heavy use) shared with alcohol 
and 
smoking. Caffeine and tobacco use and use disorders are associated with and substantially 
influenced by genetic factors unique to these licit 
drugs. The magnitude of heritability for 
caffeine use disorder markers appears to be similar to that 
for alcohol 
and tobacco use disorder 
markers. 


Culture-Related Diagnostic Issues 


Consumption of caffeine is affected by geographic origin, cultural 
context, lifestyle, social 
behavior, and economic status. The type of caffeinated beverage preferred (e.g., tea; 
coffee; 
carbonated sodas containing caffeine; 
mate 
[a beverage made from 
the herb yerba mate]) and the 
mode of preparation vary globally, leading to marked differences in the amounts and types of 
compounds in a  cup  of coffee, tea, or mate. These differences must 
be considered when 
assessing the quantity of caffeine ingested. 


Association With Suicidal 
Thoughts or Behavior 


No research specifically addresses the relationship between caffeine use disorder and suicidal 
thoughts or behavior. There is contradictory evidence regarding caffeine consumption; 
namely, 
that 
high levels of caffeine consumption either may be associated with increased risk for suicidal 
thoughts or behavior or may be protective for suicidal thoughts or behavior. 



913 


Functional 
Consequences of Caffeine Use Disorder 


One U.S. population survey found that 
those who fulfilled the criteria for caffeine use disorder 
were more likely to report 
greater caffeine-related distress, feeling bad or guilty about 
caffeine 
use, sleep problems, anxiety, depression, and stress. A greater number of total 
symptoms 
endorsed also predicted these negative outcomes. Caffeine use disorder may predict 
greater use 
of caffeine during pregnancy. 


Differential 
Diagnosis 


Nonproblematic 
use 
of 
caffeine. 
The distinction between nonproblematic use of caffeine and 
caffeine use disorder can be difficult 
to make because social, behavioral, or psychological 
problems may be difficult 
to attribute to the substance, especially in the context 
of use of other 
substances. Regular, heavy caffeine use that 
can result 
in tolerance and withdrawal 
is relatively 
common, which by itself should not be sufficient for making a diagnosis. 


Other stimulant 
use 
disorder. 


Problems related to use of other stimulant 
medications or substances 


may approximate the features of caffeine use disorder. 
Anxiety 
disorders. 
Chronic heavy caffeine use may mimic generalized anxiety disorder, and acute 
caffeine consumption may produce and mimic panic attacks. 


Comorbidity 


Comorbidities associated with caffeine use disorder include daily cigarette smoking, cannabis 
use disorder, and a family or personal 
history of alcohol 
use disorder. Compared with individuals 
in the general 
population, rates of caffeine use disorder are higher among those seeking treatment 
for problematic caffeine use; 
individuals who use tobacco; 
high school 
and college students; 
and 
those with histories of alcohol 
or illicit 
drug misuse. Features of caffeine use disorder may be 
positively associated with several 
diagnoses: 
major depression, generalized anxiety disorder, 
panic disorder, antisocial personality disorder, and alcohol, cannabis, and cocaine use disorders. 


Internet Gaming 
Disorder 


Proposed Criteria 


Persistent 
and 
recurrent 
use 
of 
the 
Internet 
to 
engage 
in 
games, 
often 
with 
other 
players, 
leading 
to 
clinically significant 
impairment 
or distress as indicated 
by five 
(or 
more) of 
the 
following 
in 
a 
12-month 
period: 


1. 
Preoccupation 
with 
Internet 
games. 
(The 
individual thinks about 
previous gaming 
activity or anticipates playing 
the 
next 
game; 
Internet 
gaming 
becomes the 
dominant 
activity in 
daily life.) 
Note: 
This disorder is distinct 
from Internet 
gambling, 
which 
is included 
under 
gambling 
disorder. 

2. 
Withdrawal symptoms when 
Internet 
gaming 
is taken 
away. 
(These 
symptoms 
are 
typically described 
as irritability, 
anxiety, 
or sadness, 
but 
there 
are 
no 
physical signs of 
pharmacological withdrawal.) 
3. 
Tolerance the 
need 
to 
spend 
increasing 
amounts of 
time 
engaged 
in 
Internet 
games. 
4. 
Unsuccessful attempts to 
control the 
participation 
in 
Internet 
games. 
5. 
Loss of 
interests in 
previous hobbies and 
entertainment 
as a 
result 
of, 
and 
with 
the 
exception 
of, 
Internet 
games. 
914 


6. 
Continued 
excessive 
use 
of 
Internet 
games despite 
knowledge 
of 
psychosocial 
problems. 
7. 
Has deceived 
family members, 
therapists, 
or others regarding 
the 
amount 
of 
Internet 
gaming. 
8. 
Use 
of 
Internet 
games to 
escape 
or relieve 
a 
negative 
mood 
(e.g., 
feelings of 
helplessness, 
guilt, 
anxiety). 
9. 
Has jeopardized 
or lost 
a 
significant 
relationship, 
job, 
or educational or career 
opportunity because 
of 
participation 
in 
Internet 
games. 
Note: 
Only nongambling 
Internet 
games are 
included 
in 
this disorder. 
Use 
of 
the 
Internet 
for required 
activities in 
a 
business or profession 
is not 
included; 
nor is the 
disorder intended 
to 
include 
other recreational or social Internet 
use. 
Similarly, 
sexual Internet 
sites are 
excluded. 


Specify current 
severity: 


Internet 
gaming 
disorder can 
be 
mild, 
moderate, 
or severe 
depending 
on 
the 
degree 
of 
disruption 
of 
normal activities. 
Individuals with 
less severe 
Internet 
gaming 
disorder may exhibit 
fewer symptoms and 
less disruption 
of 
their lives. 
Those 
with 
severe 
Internet 
gaming 
disorder will have 
more 
hours spent 
on 
the 
computer and 
more 
severe 
loss of 
relationships or career or school 
opportunities. 


Gambling disorder is currently the only non-substance-related disorder included in the DSM5 
Section II chapter  Substance-Related and Addictive Disorders.  However, there are other 
behavioral 
disorders that 
show some similarities to substance use disorders and gambling 
disorder for which the word addiction 
is commonly used in nonmedical 
settings, and the one 
condition with a considerable literature is the compulsive playing of Internet 
games. Internet 
gaming has been reportedly defined as an  addiction  by the Chinese government 
and is 
considered a public health threat 
in South Korea, where treatment 
and prevention systems have 
been set 
up. Reports of treatment 
of this condition have appeared in medical 
journals, mostly 
from Asian countries, but also in the United States and other high-income countries. 


The DSM-5 work group reviewed more than 240 articles and found some behavioral 
similarities of Internet gaming to gambling disorder and to substance use disorders. The literature 
suffers, however, from 
lack of a standard definition from 
which to derive prevalence data. An 
understanding of the natural 
histories of cases, with or without 
treatment, is also missing. The 



literature does describe many underlying similarities to substance addictions, including aspects 
of tolerance, withdrawal, repeated unsuccessful 
attempts to cut 
back or quit, and impairment 
in 
normal 
functioning. Further, the seemingly high prevalence rates, both in Asian countries and in 
the West, justified inclusion of this disorder in Section III of DSM-5 and in the Mental, 
Behavioural, and Neurodevelopmental 
Disorders chapter in 
ICD-11. Note that 
since the 
publication of DSM-5, the number of clinical 
reports has continued to accumulate, but 
many of 
the issues remain unresolved. 


Internet 
gaming disorder has achieved significant 
public health importance, and additional 
research may eventually lead to evidence that 
Internet 
gaming disorder (also commonly referred 
to as Internet 
use disorder, Internet addiction, or gaming addiction) has merit 
as an independent 
disorder. As with gambling disorder, there should be epidemiological 
studies to determine 
prevalence, clinical 
course, possible genetic influence, and potential 
biological 
factors based on, 
for example, brain imaging data. 


Diagnostic Features 


The essential 
feature of Internet 
gaming disorder is a pattern of excessive and prolonged 
participation in Internet 
gaming that 
results in a cluster of cognitive and behavioral 
symptoms, 
including progressive loss of control over gaming, tolerance, and withdrawal 


915 


symptoms, analogous to the symptoms of substance use disorders. These Internet-based games 
typically involve competition between groups of players who are often in different 
global 
regions, so that 
extended duration of play is encouraged by time-zone independence. Although 
Internet 
gaming disorder most 
often involves specific Internet 
games with multiplayer 
competition, it 
can include non-Internet 
computerized off-line games as well, although these 
have been less researched. The Internet 
gaming often includes a significant 
aspect 
of social 
interactions during play, and the team 
aspects of play appear to be a key motivation. Attempts to 
direct the individual toward schoolwork or interpersonal activities are strongly resisted. 


Individuals with Internet 
gaming disorder continue to sit 
at 
a computer and engage in gaming 
activities despite neglect 
of other activities. They typically devote 8 10 hours or more per day to 
this activity and at 
least 
30 hours per week. If they are prevented from 
using a computer and 
returning to the game, they become agitated and angry. They often go for long periods without 
food or sleep. Normal obligations, such as school or work, or family obligations are neglected. 


Until 
the optimal 
criteria and threshold for diagnosis are determined empirically, 
conservative definitions ought 
to be used, such that 
diagnoses are considered for endorsement 
of 
five or more of nine criteria. 


Associated Features 


Although no consistent 
personality types associated with Internet 
gaming disorder have been 
identified, negative affectivity, detachment, antagonism, disinhibition, and psychoticism 
have 
been associated with the disorder. Individuals with compulsive Internet 
gaming have 
demonstrated brain activation in specific regions triggered by exposure to the Internet 
game but 
not limited to reward system structures. 



Prevalence 


The mean prevalence of 12-month Internet 
gaming disorder is estimated as 4.7% across multiple 
countries, with a range of 0.7% to 15.6% across studies. Research using the DSM-5 proposed 
criteria suggests that 
prevalence is similar in Asian and Western countries. In the United States, 
based on large Internet-based surveys, the prevalence of DSM-5 Internet 
gaming disorder is 1% 
or lower. An international 
meta-analysis of 16 studies found a pooled prevalence of Internet 
gaming disorder among adolescents of 4.6%, with adolescent 
boys/men generally reporting a 
higher prevalence rate (6.8%) than adolescent girls/women (1.3%). 


Risk and Prognostic Factors 


Environmental. 
Computer availability with Internet 
connection allows access to the types of 


games with which Internet gaming disorder is most often associated. 
Genetic 
and 
physiological. 
Adolescent 
men seem 
to be at 
greatest 
risk of developing Internet 
gaming disorder. 


Sex- and Gender-Related Diagnostic Issues 


Internet 
gaming disorder appears to be more common in adolescent 
and young adult 
men than 
adolescent 
and young adult 
women. Adolescent 
boys ages 12 15 years also may be at 
greater 
risk of adverse effects of disordered gaming (e.g., lower school 
grades, loneliness). There may 
also be gender differences in the types of games played, in that 
adolescent 
girls ages 12 15 tend 
to choose games that 
include puzzles, music, and social 
and educational 
themes, whereas 
adolescent 
boys of the same age more often choose action, fighting, strategy, and role-playing 
games that may have greater addictive potential. 


916 


Association With Suicidal 
Thoughts or Behavior 


Few studies specifically address suicide in individuals diagnosed with Internet 
gaming disorder, 
but 
studies on a broader phenotype of problematic Internet 
and online gaming behaviors are 
available. A nationally representative household survey of Australian youth ages 11 17 years 
(Young Minds Matter) found that 
problem 
Internet 
and online gaming behavior was associated 
with higher risk of suicide attempt 
in the prior year. After controlling for demographics, 
depression, family support, and self-esteem, a survey study of 9,510 Taiwanese students ages 
12 18 years found that 
Internet 
addiction, including online gaming, was associated with suicidal 
thoughts and suicide attempt. In a representative sample of 8,807 students from 
randomly 
selected European schools, 3.62% had Internet 
gaming disorder (using DSM-5 criteria), and 
3.11% of the students were considered to have pathological 
Internet 
use but 
were not 
gamers. 
Both groups showed similarly increased risks for emotional 
symptoms, conduct 
disorder, 
hyperactivity/inattention, self-injurious behaviors, and suicidal 
thoughts and behavior. The 
mental 
health effects of problematic Internet 
use, including suicidal 
thoughts or behavior, appear 
to be related to and perhaps mediated by the impact of problematic Internet use on sleep. 


Functional 
Consequences of Internet Gaming Disorder 



Internet 
gaming disorder may lead to school 
failure, job loss, or marriage failure. The 
compulsive gaming behavior tends to crowd out 
normal 
social, scholastic, and family activities. 
Students may show declining grades and eventually failure in school. Family responsibilities 
may be neglected. 


Differential 
Diagnosis 


Excessive use of the Internet 
not 
involving playing of online games (e.g., excessive use of social 
media, such as Facebook; 
viewing pornography online) is not 
considered analogous to Internet 
gaming disorder, and future research on other excessive uses of the Internet would need to follow 
similar guidelines as suggested 
herein. Excessive gambling online may qualify for a separate 
diagnosis of gambling disorder. 


Comorbidity 


Health may be neglected due to compulsive gaming. Other diagnoses that 
may be associated 
with Internet 
gaming disorder include major depressive disorder, ADHD, and obsessive-
compulsive disorder. 


Neurobehavioral 
Disorder Associated 
With 
Prenatal 
Alcohol 
Exposure 


Proposed Criteria 


A. 
More 
than 
minimal exposure 
to 
alcohol during 
gestation, 
including 
prior to 
pregnancy recognition. 
Confirmation 
of 
gestational exposure 
to 
alcohol may be 
obtained 
from maternal self-report 
of 
alcohol use 
in 
pregnancy, 
medical or other 
records, 
or clinical observation. 
B. 
Impaired 
neurocognitive 
functioning 
as manifested 
by one 
or more 
of 
the 
following: 
1. 
Impairment 
in 
global intellectual performance 
(i.e., 
IQ 
of 
70 
or below, 
or a 
standard 
score 
of 
70 
or below on 
a 
comprehensive 
developmental 
assessment). 
2. 
Impairment 
in 
executive 
functioning 
(e.g., 
poor planning 
and 
organization; 
inflexibility; 
difficulty with 
behavioral inhibition). 
917 


3. 
Impairment 
in 
learning 
(e.g., 
lower academic achievement 
than 
expected 
for 
intellectual level; 
specific learning 
disability). 
4. 
Memory impairment 
(e.g., 
problems remembering 
information 
learned 
recently; 
repeatedly making 
the 
same 
mistakes; 
difficulty remembering 
lengthy verbal instructions). 

5. 
Impairment 
in 
visual-spatial reasoning 
(e.g., 
disorganized 
or poorly planned 
drawings or constructions; 
problems differentiating 
left 
from right). 
C. 
Impaired 
self-regulation 
as manifested 
by one 
or more 
of 
the 
following: 
1. 
Impairment 
in 
mood 
or behavioral regulation 
(e.g., 
mood 
lability; 
negative 
affect 
or irritability; 
frequent 
behavioral outbursts). 
2. 
Attention 
deficit 
(e.g., 
difficulty shifting 
attention; 
difficulty sustaining 
mental 
effort). 
3. 
Impairment 
in 
impulse 
control (e.g., 
difficulty waiting 
turn; 
difficulty complying 
with 
rules). 
D. 
Impairment 
in 
adaptive 
functioning 
as manifested 
by two 
or more 
of 
the 
following, 
one 
of 
which 
must 
be 
(1) or (2): 
1. 
Communication 
deficit 
(e.g., 
delayed 
acquisition 
of 
language; 
difficulty 
understanding 
spoken 
language). 
2. 
Impairment 
in 
social communication 
and 
interaction 
(e.g., 
overly friendly with 
strangers; 
difficulty reading 
social cues; 
difficulty understanding 
social 
consequences). 
3. 
Impairment 
in 
daily living 
skills (e.g., 
delayed 
toileting, 
feeding, 
or bathing; 
difficulty managing 
daily schedule). 
4. 
Impairment 
in 
motor skills (e.g., 
poor fine 
motor development; 
delayed 
attainment 
of 
gross motor milestones or ongoing 
deficits in 
gross motor 
function; 
deficits in 
coordination 
and 
balance). 
E. 
Onset 
of 
the 
disorder (symptoms in 
Criteria 
B, 
C, 
and 
D) occurs in 
childhood. 
F. 
The 
disturbance 
causes clinically significant 
distress or impairment 
in 
social, 
academic, 
occupational, 
or other important 
areas of 
functioning. 
G. 
The 
disorder is not 
better explained 
by the 
direct 
physiological effects associated 
with 
postnatal use 
of 
a 
substance 
(e.g., 
a 
medication, 
alcohol or other drugs), 
a 
general medical condition 
(e.g., 
traumatic brain 
injury, 
delirium, 
dementia), 
another known 
teratogen 
(e.g., 
fetal hydantoin 
syndrome), 
a 
genetic condition 
(e.g., 
Williams syndrome, 
Down 
syndrome, 
Cornelia 
de 
Lange 
syndrome), 
or 
environmental neglect. 
Alcohol 
is a neurobehavioral 
teratogen, and prenatal 
alcohol 
exposure has teratogenic effects 
on central 
nervous system 
(CNS) development 
and subsequent 
function. Neurobehavioral 
disorder associated with prenatal 
alcohol 
exposure 
(ND-PAE) is a new clarifying term, intended 
to encompass the full 
range of developmental 
disabilities associated with exposure to alcohol 
in 
utero. ND-PAE 
may be diagnosed both in the absence and in the presence of the physical 
effects 
of prenatal 
alcohol 
exposure (e.g., facial 
dysmorphology required for a diagnosis of fetal 
alcohol 
syndrome). 


Diagnostic Features 


The essential 
features of ND-PAE 
are the manifestation of impairment 
in neurocognitive, 



behavioral, and adaptive functioning associated with prenatal 
alcohol 
exposure. Impairment 
can 
be documented based on past 
diagnostic evaluations (e.g., psychological 
or educational 
assessments) or medical 
records, reports by the individual 
or informants, and/or observation by a 
clinician. 


A clinical 
diagnosis of fetal 
alcohol 
syndrome, including specific prenatal 
alcohol-related 
facial dysmorphology and growth retardation, can be used as evidence of 


918 


significant 
levels of prenatal 
alcohol 
exposure; 
specific guidelines for facial 
dysmorphology 
have been developed for diverse ethnoracial 
physiognomies. Although both animal 
and human 
studies have documented adverse effects of lower levels of drinking, identifying how much 
prenatal 
exposure is needed to significantly impact 
neurodevelopmental 
outcome remains 
challenging. Data suggest 
that 
a history of more than minimal 
gestational 
exposure prior to 
pregnancy recognition and/or following pregnancy recognition may be required. More than 
minimal 
exposure is defined as greater than 13 drinks per month during pregnancy or more than 
2 drinks on any one occasion. Identifying a minimal 
threshold of drinking during pregnancy will 
require consideration of a variety of factors known to affect 
exposure and/or interact 
to influence 
developmental 
outcomes, including stage of prenatal 
development, gestational 
smoking, 
maternal 
and fetal 
genetics, and maternal 
physical 
status (i.e., age, health, and certain obstetric 
problems). 


Symptoms of ND-PAE 
include marked impairment 
in global 
intellectual 
performance (IQ) or 
neurocognitive impairments in any of the following areas: 
executive functioning, learning, 
memory, and/or visual-spatial 
reasoning. Impairments in self-regulation are present 
and may 
include impairment 
in mood or behavioral 
regulation, attention deficit, or impairment 
in impulse 
control. Finally, impairments in adaptive functioning include communication deficits and 
impairment 
in social 
communication and interaction. Impairment 
in daily living (self-help) skills 
and impairment 
in motor skills may be present. As it 
may be difficult 
to obtain an accurate 
assessment 
of the neurocognitive abilities of very young children, it 
is appropriate to defer a 
diagnosis for children 3 years of age and younger. 


Associated Features 


Associated features vary depending on age, degree of alcohol 
exposure, and the individual s 
environment. An individual 
can be diagnosed with this disorder regardless of socioeconomic or 
cultural 
background. However, ongoing parental 
alcohol/substance misuse, parental 
mental 
illness, exposure to domestic or community violence, neglect 
or abuse, disrupted caregiving 
relationships, multiple out-of-home placements, and lack of continuity in medical 
or mental 
health care are often present. 


Prevalence 


In the United States, the prevalence of ND-PAE 
(encompassing fetal 
alcohol 
spectrum 
disorders) 
has been estimated as 15.2/1,000 (range: 
11.3 50.0/1,000), with higher estimates derived when 
only children with full 
evaluations were included (31.1 98.5/1,000). When vulnerable 
subpopulations are considered, rates of ND-PAE 
can be much higher (e.g., among children in 



care settings, 251.5/1,000), according to a meta-analysis of data from 
multiple countries. In 
2012, the mean global 
prevalence of fetal 
alcohol 
spectrum 
disorder in the general 
population 
was 7.7 per 1,000 individuals, with a prevalence of 8.8 per 1,000 in the region of the Americas 
(including the United States). 


Development and Course 


Among individuals with prenatal 
alcohol 
exposure, evidence of CNS 
dysfunction varies 
according to developmental 
stage. Although about 
one-half of young children prenatally exposed 
to alcohol 
show marked developmental 
delay in the first 
3 years of life, other children affected 
by prenatal 
alcohol 
exposure may not 
exhibit 
signs of CNS 
dysfunction until 
they are preschool-
or school-age. Additionally, impairments in higher order cognitive processes (i.e., executive 
functioning), which are often associated with prenatal 
alcohol 
exposure, may be more easily 
assessed in older children. When children reach school 
age, learning difficulties, impairment 
in 
executive function, and problems with integrative language functions usually emerge more 
clearly, and both social 
skills deficits and challenging behavior may become more evident. In 
particular, as school and other requirements 


919 


become more complex, greater deficits are noted. Because of this, the school 
years represent 
the 
ages at which a diagnosis of ND-PAE would be most likely. 


Risk and Prognostic Factors 


Environmental. 


Low socioeconomic status and low educational 
level 
in the mother are risk 
factors for fetal 
alcohol 
syndrome. This association is related to social, structural, and 
psychological 
factors that 
may increase the risk of maternal 
drinking or worsen its impact, 
including social 
determinants of health, such as the high concentration of liquor stores in low-
income, ethnoracially segregated communities. 


Culture-Related Diagnostic Issues 


Socioeconomic and cultural 
factors affect 
the consumption of alcohol 
during pregnancy, which 
ranges globally from 
0.2% in the Eastern Mediterranean region to 25.2% in the European region. 
Individuals belonging to ethnic groups that 
have higher proportions of certain alleles of alcohol-
metabolizing enzymes (e.g., of aldehyde dehydrogenase 2) may be less likely to exhibit 
the 
effects of prenatal alcohol exposure. 


Association With Suicidal 
Thoughts or Behavior 


Suicide is a high-risk outcome, with rates increasing significantly in late adolescence and early 
adulthood. Analyses of the Canadian national 
fetal 
alcohol 
spectrum 
disorder (FASD) database 
show that 
among individuals with FASD who have impaired affect 
regulation, there is a 
markedly higher risk of suicidal 
thoughts or behavior. In an Alberta-based registry, it 
was found 
that 
individuals with fetal 
alcohol 
syndrome are at 
markedly increased risk for premature death, 
with 15% dying from 
suicide. In California, a study of 54 adolescents ages 13 18 years with 



FASD also demonstrated markedly higher rates of suicidal 
thoughts and serious attempts (all 
by 
boys) compared with the general 
U.S. adolescent 
population. In a Canadian survey, the mothers 
of individuals with FASD were over six times as likely to die by suicide and almost 
five times 
more likely to attempt 
suicide after giving birth to a child with FASD compared with mothers 
whose child did not 
have FASD, suggesting that 
the increased rates of suicidal 
ideation and 
suicide attempts among youth with FASD may be mediated by family factors (genetic and/or 
environmental), in addition to any risk conferred by the FASD condition itself. 


Functional 
Consequences of Neurobehavioral 
Disorder Associated 
With Prenatal 
Alcohol 
Exposure 


The CNS 
dysfunction seen in individuals with ND-PAE 
often leads to decrements in adaptive 
behavior and to maladaptive behavior with lifelong consequences. Abnormalities have been 
associated with ND-PAE 
in multiple organ systems, including the heart, kidney, liver, 
gastrointestinal 
tract, and endocrine systems. Individuals affected by prenatal 
alcohol 
exposure 
have a higher prevalence of disrupted school experiences, poor employment records, trouble with 
the law, confinement (legal or psychiatric), and dependent living conditions. 


Differential 
Diagnosis 


Other considerations include maternal 
exposure to other substances during the prenatal 
period; 
poor prenatal 
care; 
the physiological 
effects of postnatal 
substance use, such as a medication, 
alcohol, or other substances; 
disorders due to another medical 
condition, such as traumatic brain 
injury or other neurocognitive disorders (e.g., delirium, major neurocognitive disorder 
[dementia]); and environmental neglect. 


Genetic conditions such as Williams syndrome, Down syndrome, or Cornelia de Lange 
syndrome and other teratogenic conditions such as fetal hydantoin syndrome and 


920 


maternal 
phenylketonuria may have similar physical 
and behavioral 
characteristics. A careful 
review of prenatal 
exposure history is needed to clarify the teratogenic agent, and an evaluation 
by a clinical 
geneticist 
may be needed to distinguish physical 
characteristics associated with 
these and other genetic conditions. 


Comorbidity 


Mental 
health problems have been identified in more than 90% of individuals with histories of 
significant 
prenatal 
alcohol 
exposure. The most 
common co-occurring diagnosis is attentiondeficit/
hyperactivity disorder, but 
research has shown that 
individuals with ND-PAE 
differ in 
neuropsychological 
characteristics and in their responsiveness to pharmacological 
interventions. 
Other high- probability co-occurring disorders include oppositional 
defiant 
disorder and conduct 
disorder, but 
the appropriateness of these diagnoses should be weighed in the context 
of the 
significant 
impairments in general 
intellectual 
and executive functioning that 
are often associated 
with prenatal 
alcohol 
exposure. Mood symptoms, including symptoms of bipolar disorder and 
depressive disorders, have been described. History of prenatal 
alcohol 
exposure is associated 
with an increased risk for later tobacco, alcohol, and other substance use disorders. 



Suicidal 
Behavior Disorder 


Proposed Criteria 


A. 
Within 
the 
last 
24 
months, 
the 
individual has made 
a 
suicide 
attempt. 
Note: 
A 
suicide 
attempt 
is a 
self-initiated 
sequence 
of 
behaviors by an 
individual 
who, 
at 
the 
time 
of 
initiation, 
expected 
that 
the 
set 
of 
actions would 
lead 
to 
his or 
her own 
death. 
(The 
 time 
of 
initiation  is the 
time 
when 
a 
behavior took place 
that 
involved 
applying 
the 
method.) 


B. 
The 
act 
does not 
meet 
criteria 
for nonsuicidal self-injury that 
is, 
it 
does not 
involve 
self-injury directed 
to 
the 
surface 
of 
the 
body undertaken 
to 
induce 
relief 
from a 
negative 
feeling/cognitive 
state 
or to 
achieve 
a 
positive 
mood 
state. 
C. 
The 
diagnosis is not 
applied 
to 
suicidal ideation 
or to 
preparatory acts. 
D. 
The 
act 
was not 
initiated 
during 
a 
state 
of 
delirium or confusion. 
E. 
The 
act 
was not 
undertaken 
solely for a 
political or religious objective. 
Specify 
if: 
Current: 
Not 
more 
than 
12 
months since 
the 
last 
attempt. 
In 
early 
remission: 
12 24 
months since 
the 
last 
attempt. 


Note: 
ICD-10-CM codes to 
indicate 
whether suicidal behavior is part 
of 
the 
current 
clinical presentation 
(T14.91A 
for initial encounter and 
T14.91D 
for subsequent 
encounters) and/or whether there 
has been 
a 
prior history of 
suicidal behavior (Z91.51) 
are 
available 
for clinical use 
to 
accompany any DSM-5 
diagnosis; 
in 
addition, 
the 
codes 
can 
be 
recorded 
in 
the 
absence 
of 
a 
DSM-5 
diagnosis. 
The 
definition 
of 
these 
codes is 
included 
in 
Section 
II, 
 Other Conditions That 
May Be 
a 
Focus of 
Clinical Attention  (see 
 Suicidal Behavior ). 


Specifiers 


Suicidal 
behavior is often categorized in terms of violence of the method. Generally, overdoses 
with legal 
or illegal 
substances are considered nonviolent 
in method, whereas jumping, gunshot 
wounds, and other methods are considered violent. Another dimension for classification is 
medical 
consequences of the behavior, with high-lethality attempts being defined as those 
requiring medical hospitalization beyond a visit to an emergency 


921 


department. An additional 
dimension considered includes the degree of planning versus 
impulsiveness of the attempt, a characteristic that 
might 
have consequences for the medical 
outcome of a suicide attempt. 


If the suicidal 
behavior occurred 12 24 months prior to evaluation, the condition is 
considered to be in early remission. 



Diagnostic Features 


The essential 
manifestation of suicidal 
behavior disorder is a suicide attempt. A suicide attempt 
is a behavior that 
the individual 
has undertaken with at 
least 
some intent 
to die. The behavior 
might 
or might 
not 
lead to injury or serious medical 
consequences. Several 
factors can influence 
the medical 
consequences of the suicide attempt, including poor planning, lack of knowledge 
about 
the lethality of the method chosen, low intentionality or ambivalence, or chance 
intervention by others after the behavior has been initiated. These should not 
be considered in 
assigning the diagnosis. 


Determining the degree of intent 
can be challenging. Individuals might 
not 
acknowledge 
intent, especially in situations where doing so could result 
in hospitalization or cause distress to 
loved ones. Markers of risk include degree of planning, including selection of a time and place to 
minimize rescue or interruption; 
the individual s mental 
state at 
the time of the behavior, with 
acute agitation being especially concerning; 
recent 
discharge from 
inpatient 
care; 
or recent 
discontinuation of a mood stabilizer such as lithium 
or an antipsychotic such as clozapine in the 
case of schizophrenia. Examples of environmental 
 triggers  include recently learning of a 
potentially fatal 
medical 
diagnosis such as cancer, experiencing the sudden and unexpected loss 
of a close relative or partner, loss of employment, or displacement 
from 
housing. Conversely, 
features such as talking to others about 
future events or preparedness to sign a contract 
for safety 
are less reliable indicators. 


In order for the criteria to be met, the individual 
must 
have made at 
least 
one suicide attempt. 
Suicide attempts can include behaviors in which, after initiating the suicide attempt, the 
individual 
changed his or her mind or someone intervened. For example, an individual 
might 
intend to ingest 
a given amount 
of medication or poison, but 
either stop or be stopped by another 
before ingesting the full 
amount. If the individual 
is dissuaded by another or changes his or her 
mind before initiating the behavior, the diagnosis should not 
be made. The acts qualifying for a 
diagnosis of suicidal 
behavior disorder should not 
have been initiated exclusively during a state 
of delirium 
or confusion. If the individual 
deliberately became intoxicated before initiating the 
suicidal 
behavior in order to reduce anticipatory anxiety and to minimize interference with the 
intended behavior, the diagnosis can still be made. 


Currently there are no clinical 
instruments that 
yield positive predictive values sufficient 
to 
make them 
useful 
tools for predicting suicidal 
behavior at 
the patient 
level. It 
is not 
surprising 
that 
single clinical 
or biological 
factors are poor indicators of suicide risk, because suicidal 
behavior emerges from 
a convergence of multiple risk factors. Moreover, given the clinical 
heterogeneity of suicidal 
behavior, it 
is likely that 
there are multiple pathways to suicidal 
behavior that 
can only be captured if this heterogeneity is considered. Similarly, numerous 
biomarkers have been studied, but no robust predictor has emerged. 


Development and Course 


Suicidal 
behavior disorder can occur at 
any time in the life span but 
is rarely seen in children 
under the age of 5. Approximately 25% 30% of persons who attempt 
suicide will 
go on to make 
more attempts. There is significant 
variability in terms of frequency, method, and lethality of 
attempts. However, this is not 
different 
from 
what 
is observed in other illnesses, such as major 
depressive disorder, in which frequency of episode, subtype of episode, and impairment 
for a 
given episode can vary significantly. 



922 


Risk and Prognostic Factors 


Genetic 
and 
physiological. 
The largest 
genome-wide association study of suicide attempt 
to date, 
from 
the Psychiatric Genomics Consortium, found that 
the genetic risk for depression increases 
the risk for suicide attempt 
across diagnostic cohorts with major depressive disorder, bipolar 
disorder, and schizophrenia. In other words, across diagnostic categories, attempters carry more 
risk alleles for depression than nonattempters, rather than simply for their primary psychiatric 
diagnosis. These results suggest 
that 
the genetic associations with suicide attempt 
are partly 
unique and partly shared with the genetic associations with depression. 


Culture-Related Diagnostic Issues 


Cultural 
contexts affect 
the frequency and form 
of suicidal 
behavior disorder, including 
variations in incidence and prevalence, methods used (e.g., poisoning with pesticides in low-
income countries; 
gunshot 
wounds in the southwestern United States), motivations, 
circumstances, and meanings. These patterns vary over time, by migrant 
or ethnic group, and by 
service setting. Culturally mediated social 
stressors and predicaments such as family 
breakdowns, perceived loss of dignity or interpersonal 
status, conflicting intergenerational 
roles 
and expectations due to differential 
acculturation, changing levels of sociocultural 
integration, 
stigma and self-stigma about 
suicide, and systemic discrimination and structural 
inequity 
(institutionalized socioeconomic bias and oppression) may contribute to the risk of suicidal 
behavior disorder. Attitudes toward suicide and suicidal 
behaviors are influenced by historical, 
environmental, economic, political, legal, social, cultural, moral, and spiritual 
or religious 
factors. For example, in a longitudinal 
U.S. sample followed across generations, parental 
belief 
(self-identified as mostly Protestant 
and Catholic) in the importance of religion was associated 
with lower risk of suicidal 
behavior in their offspring, independent 
of an offspring s own belief 
about 
religious importance and other known parental 
factors, such as parental 
depression, 
suicidal 
behavior, and divorce. The reasons for suicide attempts and choice of suicide methods 
may have cultural 
significance, which may be associated with specific individual 
and social 
responses (e.g., of stigma, shame, or respect). 


Sex- and Gender-Related Diagnostic Issues 


Suicidal 
behavior disorder varies in prevalence and form 
across sex and gender. On average, 
suicides are about 
twice as common in men compared with women, although the prevalence ratio 
varies by country and cultural 
context. Estimates also vary because the intent 
of self-harm 
behaviors is not 
always clearly measured; 
however, suicidal 
behavior that 
does not 
result 
in 
death is more common in women than in men. Men generally use more lethal 
methods such as 
gunshots and hanging, whereas less lethal 
means such as self-poisoning are more common in 
women. The frequency of suicidal 
behaviors is higher in women (i.e., the average number of 
suicide attempts for a woman is generally higher than the average number for a man), but 
this 
could be explained by the more frequent 
use of less lethal 
methods among women. Suicide rates 
among individuals who identify as transgender are high, and transgender individuals are also at 
higher risk for suicidal behavior than cisgender individuals. 



Diagnostic Markers 


Laboratory abnormalities consequent 
to the suicidal 
attempt 
are often evident. Suicidal 
behavior 
that 
leads to blood loss can be accompanied by anemia, hypotension, or shock. Overdoses might 
lead to coma or obtundation and associated laboratory abnormalities such as electrolyte 
imbalances. 


923 


Comorbidity 


Suicidal 
behavior disorder is seen in the context 
of a variety of mental 
disorders, most 
commonly 
bipolar disorder, major depressive disorder, schizophrenia, schizoaffective disorder, anxiety 
disorders (in particular, panic disorders associated with catastrophic content 
and PTSD 
flashbacks), substance use disorders (especially alcohol 
use disorders), borderline personality 
disorder, antisocial personality disorder, eating disorders, and adjustment disorders. 


Nonsuicidal 
Self-Injury Disorder 


Proposed Criteria 


A. 
In 
the 
last 
year, 
the 
individual has, 
on 
5 
or more 
days, 
engaged 
in 
intentional 
self-inflicted 
damage 
to 
the 
surface 
of 
his or her body of 
a 
sort 
likely to 
induce 
bleeding, 
bruising, 
or pain 
(e.g., 
cutting, 
burning, 
stabbing, 
hitting, 
excessive 
rubbing), 
with 
the 
expectation 
that 
the 
injury will lead 
to 
only minor or moderate 
physical harm (i.e., 
there 
is no 
suicidal intent). 
Note: 
The 
absence 
of 
suicidal intent 
has either been 
stated 
by the 
individual or 
can 
be 
inferred 
by the 
individual s repeated 
engagement 
in 
a 
behavior that 
the 
individual knows, 
or has learned, 
is not 
likely to 
result 
in 
death. 


B. 
The 
individual engages in 
the 
self-injurious behavior with 
one 
or more 
of 
the 
following 
expectations: 
1. 
To 
obtain 
relief 
from a 
negative 
feeling 
or cognitive 
state. 
2. 
To 
resolve 
an 
interpersonal difficulty. 
3. 
To 
induce 
a 
positive 
feeling 
state. 
Note: 
The 
desired 
relief 
or response 
is experienced 
during 
or shortly after the 
self-injury, 
and 
the 
individual may display patterns of 
behavior suggesting 
a 
dependence 
on 
repeatedly engaging 
in 
it. 


C. 
The 
intentional self-injury is associated 
with 
at 
least 
one 
of 
the 
following: 
1. 
Interpersonal difficulties or negative 
feelings or thoughts, 
such 
as depression, 
anxiety, 
tension, 
anger, 
generalized 
distress, 
or self-criticism, 
occurring 
in 
the 
period 
immediately prior to 
the 
self-injurious act. 
2. 
Prior to 
engaging 
in 
the 
act, 
a 
period 
of 
preoccupation with 
the 
intended 

behavior that 
is difficult 
to 
control. 


3. 
Thinking 
about 
self-injury that 
occurs frequently, 
even 
when 
it 
is not 
acted 
upon. 
D. 
The 
behavior is not 
socially sanctioned 
(e.g., 
body piercing, 
tattooing, 
part 
of 
a 
religious or cultural ritual) and 
is not 
restricted 
to 
picking 
a 
scab 
or nail biting. 
E. 
The 
behavior or its consequences cause 
clinically significant 
distress or 
interference 
in 
interpersonal, 
academic, 
or other important 
areas of 
functioning. 
F. 
The 
behavior does not 
occur exclusively during 
psychotic episodes, 
delirium, 
substance 
intoxication, 
or substance 
withdrawal. 
In 
individuals with 
a 
neurodevelopmental disorder, 
the 
behavior is not 
part 
of 
a 
pattern 
of 
repetitive 
stereotypies. 
The 
behavior is not 
better explained 
by another mental disorder or 
medical condition 
(e.g., 
psychotic disorder, 
autism spectrum disorder, 
intellectual 
developmental disorder [intellectual disability], 
Lesch-Nyhan 
syndrome, 
stereotypic movement 
disorder with 
self-injury, 
trichotillomania 
[hair-pulling 
disorder], 
excoriation 
[skin-picking] 
disorder). 
Note: 
ICD-10-CM codes to 
indicate 
whether nonsuicidal self-injury is part 
of 
the 
current 
clinical presentation 
(R45.88) 
and/or whether there 
has been 
a 
prior history of 
nonsuicidal 


924 


self-injury (Z91.52) 
are 
available 
for clinical use 
to 
accompany any DSM-5 
diagnosis; 
in 
addition, 
the 
codes can 
be 
recorded 
in 
the 
absence 
of 
a 
DSM-5 
diagnosis. 
The 
definition 
of 
these 
codes is included 
in 
Section 
II, 
 Other Conditions That 
May Be 
a 
Focus of 
Clinical Attention  (see 
 Nonsuicidal Self-Injury ). 


Diagnostic Features 


The essential 
feature of nonsuicidal 
self-injury disorder is that 
the individual 
repeatedly inflicts 
minor-to-moderate, often painful 
injuries to the surface of his or her body without 
suicidal 
intent. 
Most 
commonly, the purpose is to reduce negative emotions, such as tension, anxiety, sadness, 
or self-reproach, or less often to resolve an interpersonal 
difficulty. In some cases, the injury is 
conceived of as a deserved self-punishment. The individual 
will 
often report 
an immediate 
sensation of relief that 
occurs during the process. When the behavior occurs frequently, it 
might 
be associated with a sense of urgency and craving, the resultant 
behavioral 
pattern resembling an 
addiction. The inflicted wounds can become deeper and more numerous. 


Cutting is the most 
common method of injury and is most 
often inflicted with a knife, needle, 
razor, or other sharp object. Common areas for injury include the dorsal 
side of the forearm 
and 
frontal 
area of the thighs. A single session of injury might 
involve a series of superficial, parallel 
cuts separated by 1 or 2 centimeters on a visible or accessible location. The resulting cuts 
will often bleed and will often leave a characteristic pattern of scars. 


Other relatively common methods used include superficial 
scratching or burning of the skin, 
as well 
as self-hitting or banging, biting, and interfering with wound healing. Many will 
use 
different 
methods over time, and use of multiple methods is associated with more severe 



psychopathology, including engagement in suicide attempts. 


Many, and possibly most, of those who engage in nonsuicidal 
self-injury do not 
seek clinical 
attention. This tendency may reflect 
a reluctance to disclose self-injury due to concerns over 
stigma. In addition, many individuals who engage in these behaviors experience them 
positively 
because of the effectiveness of nonsuicidal 
self-injury in regulating negative emotion, thereby 
reducing or eliminating motivation for treatment. Children and adolescents might 
experiment 
with these behaviors but 
not 
experience relief. In such cases, youths often report 
that 
the 
procedure is painful or distressing and might then discontinue the practice. 


Associated Features 


Nonsuicidal 
self-injury disorder appears predominantly maintained by negative reinforcement, in 
that 
the behavior is reported to quickly reduce negative emotion and aversive emotional 
arousal. 
Some who engage in the behavior also report 
that 
nonsuicidal 
self-injury can quickly reduce 
unwanted dissociative experiences and even suicidal 
ideation, as well 
as serve as a way to cope 
with trauma-related symptoms such as self-directed anger and/or disgust. However, other forms 
of social 
and emotional 
reinforcement 
can also sustain the behavior, such as a desire to elicit 
reactions from others or generate positive feelings. 


Prevalence 


In an international 
meta-analysis, prevalence of nonsuicidal 
self-injury disorder was found 
overall 
to be modestly higher in girls/women than in boys/men. This is in contrast 
to suicidal 
behavior, in which the gender ratio of girls/women to boys/men is much higher. The gender 
difference for nonsuicidal 
self-injury disorder is more pronounced in clinical 
samples. Across 
cultural 
contexts, the gender ratio of nonsuicidal 
self-injury may vary, being more prevalent 
among girls/women in some contexts (e.g., among high school 
students in rural 
areas of China) 
and among boys/men in others (e.g., among youth ages 


925 


11 19 in Jordan). Nonsuicidal 
self-injury disorder is substantially more common among sexual 
minorities, especially those who identify as bisexual. 


Development and Course 


Nonsuicidal 
self-injury disorder most 
often starts in the early to mid-teen years and can continue 
for many years, with earlier ages at 
onset 
being associated with more severe manifestations. 
Nonsuicidal 
self-injury disorder may peak in late adolescence and the early 20s and then decline 
into adulthood. Additional 
prospective research is needed to outline the natural 
history of 
nonsuicidal 
self-injury disorder and the factors that 
promote or inhibit 
its course. Individuals 
often learn of the behavior on the recommendation or observation of another, through media 
outlets, and through social 
media. Individuals exposed to others who self-injure, including in 
inpatient, school, correctional, and community settings, are more likely to initiate self-injury, 
potentially through social modeling or social learning mechanisms. 


Culture-Related Diagnostic Issues 



Nonsuicidal 
self-injury disorder should not 
be diagnosed if the behavior is motivated by a widely 
accepted cultural 
practice. This is true even if the practice is only carried out 
by a minority of the 
population (e.g., engaging in self-flagellation as a collective activity during religious festivals). 
Nonsuicidal 
self-injury may be a way of expressing group belongingness rather than individual 
distress or emotion regulation, as suggested by research with  alternative  (i.e., Goth, Emo, and 
Punk) youth groups in Germany, and nonsuicidal 
self-injury disorder should also not 
be 
diagnosed in such instances. 


Association With Suicidal 
Thoughts or Behavior 


Because individuals with nonsuicidal 
self-injury can and do attempt 
suicide, it 
is important 
to 
evaluate these individuals for suicide risk and to obtain information from 
a third party 
concerning any recent 
change in stress exposure and mood. Likelihood of a suicide attempt 
has 
been associated with a history of nonsuicidal 
self-injury, with the onset 
of nonsuicidal 
self-injury 
typically preceding suicide attempts by approximately 1 2 years, as shown by research in 
clinical 
and community settings in three high-income countries. The use of multiple previous 
methods of nonsuicidal 
self-injury, high frequencies of self-injurious acts, younger age at 
onset, 
and using nonsuicidal 
self-injury to obtain relief from 
internal 
distress or for self-punishment 
are 
strongly predictive of both suicidal ideation and suicide attempts. 


Functional 
Consequences of Nonsuicidal 
Self-Injury Disorder 


The act 
of cutting might 
be performed with shared implements, raising the possibility of blood-
borne disease transmission. Severe burns, infection from 
poor care of injuries, and permanent 
scarring can also result, negatively impacting the individual. 


Differential 
Diagnosis 


Borderline 
personality 
disorder. 
Many have regarded nonsuicidal 
self-injury as pathognomonic of 
borderline personality disorder. However, although nonsuicidal 
self-injury disorder is often 
comorbid with borderline personality disorder, many individuals with nonsuicidal 
self-injury 
disorder do not 
have a personality pattern that 
meets criteria for borderline personality disorder. 
Nonsuicidal 
self-injury disorder not 
only occurs without 
borderline personality disorder but 
frequently co-occurs with many other disorders, including depressive disorders, eating disorders, 
and substance disorders. 


926 


Suicidal 
behavior. 
The differentiation between nonsuicidal 
self-injury disorder and suicidal 
behavior is based on the stated goal 
of the behavior, either as a wish to die (suicidal 
behavior) or 
to experience relief (as described in the criteria for nonsuicidal 
self-injury disorder). In contrast 
to suicidal 
behavior, nonsuicidal 
self-injury episodes are, in the short-term, typically benign in 
individuals with a history of frequent 
episodes. Further, some individuals report 
using their 
nonsuicidal self-injury to avoid attempting suicide. 


Trichotillomania 
(hair-pulling 
disorder). 
Trichotillomania is defined by self-injurious behavior 
confined to pulling out 
one s own hair, most 
commonly from 
the scalp, eyebrows, or eyelashes. 
The behavior occurs in  sessions  that 
can last 
for hours. It 
is most 
likely to occur during a 



period of relaxation or distraction. If the self-injurious behavior is confined to hair-pulling, 


trichotillomania should be diagnosed instead of nonsuicidal self-injury disorder. 
Stereotypic 
movement 
disorder. 
Stereotypic movement 
disorder involves repetitive, seemingly 
driven, and apparently purposeless motor behavior (e.g., hand shaking or waving, body rocking, 
head banging, self-biting, hitting own body) that 
can sometimes result 
in self-injury and is often 
associated with a known medical 
or genetic condition, neurodevelopmental 
disorder, or 
environmental 
factor (e.g., Lesch-Nyhan syndrome, intellectual 
developmental 
disorder, 
intrauterine alcohol 
exposure). If the self-injurious behavior meets criteria for stereotypic 
movement disorder, it should be diagnosed instead of nonsuicidal self-injury disorder. 


Excoriation 
(skin-picking) 
disorder. 
Excoriation disorder is usually directed to picking at 
an area of 
the skin that 
the individual 
feels is unsightly or a blemish, usually on the face or the scalp. If the 
self-injurious behavior is confined to skin-picking, excoriation disorder should be diagnosed 
instead of nonsuicidal self-injury disorder.